Feasibility and accuracy of computational robot-assisted partial nephrectomy planning by virtual partial nephrectomy analysis.

PubMed

Isotani, Shuji; Shimoyama, Hirofumi; Yokota, Isao; China, Toshiyuki; Hisasue, Shin-ichi; Ide, Hisamitsu; Muto, Satoru; Yamaguchi, Raizo; Ukimura, Osamu; Horie, Shigeo

2015-05-01

To evaluate the feasibility and accuracy of virtual partial nephrectomy analysis, including a color-coded three-dimensional virtual surgical planning and a quantitative functional analysis, in predicting the surgical outcomes of robot-assisted partial nephrectomy. Between 2012 and 2014, 20 patients underwent virtual partial nephrectomy analysis before undergoing robot-assisted partial nephrectomy. Virtual partial nephrectomy analysis was carried out with the following steps: (i) evaluation of the arterial branch for selective clamping by showing the vascular-supplied area; (ii) simulation of the optimal surgical margin in precise segmented three-dimensional model for prediction of collecting system opening; and (iii) detailed volumetric analyses and estimates of postoperative renal function based on volumetric change. At operation, the surgeon identified the targeted artery and determined the surgical margin according to the virtual partial nephrectomy analysis. The surgical outcomes between the virtual partial nephrectomy analysis and the actual robot-assisted partial nephrectomy were compared. All 20 patients had negative cancer surgical margins and no urological complications. The tumor-specific renal arterial supply areas were shown in color-coded three-dimensional model visualization in all cases. The prediction value of collecting system opening was 85.7% for sensitivity and 100% for specificity. The predicted renal resection volume was significantly correlated with actual resected specimen volume (r(2) = 0.745, P < 0.001). The predicted estimated glomerular filtration rate was significantly correlated with actual postoperative estimated glomerular filtration rate (r(2) = 0.736, P < 0.001). Virtual partial nephrectomy analysis is able to provide the identification of tumor-specific renal arterial supply, prediction of collecting system opening and prediction of postoperative renal function. This technique might allow urologists to compare various arterial clamping methods and resection margins with surgical outcomes in a non-invasive manner. © 2015 The Japanese Urological Association.

Commentary on "a matched comparison of perioperative outcomes of a single laparoscopic surgeon versus a multisurgeon robot-assisted cohort for partial nephrectomy." Ellison JS, Montgomery JS, Wolf Jr JS, Hafez KS, Miller DC, Weizer AZ, Department of Urology, University of Michigan, Ann Arbor, MI, USA: J Urol 2012;188(1):45-50.

PubMed

Kane, Christopher

2013-02-01

Minimally invasive nephron sparing surgery is gaining popularity for small renal masses. Few groups have evaluated robot-assisted partial nephrectomy compared to other approaches using comparable patient populations. We present a matched pair analysis of a heterogeneous group of surgeons who performed robot-assisted partial nephrectomy and a single experienced laparoscopic surgeon who performed conventional laparoscopic partial nephrectomy. Perioperative outcomes and complications were compared. All 249 conventional laparoscopic and robot-assisted partial nephrectomy cases from January 2007 to June 2010 were reviewed from our prospectively maintained institutional database. Groups were matched 1:1 (108 matched pairs) by R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines) nephrometry score, transperitoneal vs retroperitoneal approach, patient age and hilar nature of the tumor. Statistical analysis was done to compare operative outcomes and complications. Matched analysis revealed that nephrometry score, age, gender, tumor side and American Society of Anesthesia physical status classification were similar. Operative time favored conventional laparoscopic partial nephrectomy. During the study period robot-assisted partial nephrectomy showed significant improvements in estimated blood loss and warm ischemia time compared to those of the experienced conventional laparoscopic group. Postoperative complication rates, and complication distributions by Clavien classification and type were similar for conventional laparoscopic and robot-assisted partial nephrectomy (41.7% and 35.0%, respectively). Robot-assisted partial nephrectomy has a noticeable but rapid learning curve. After it is overcome the robotic procedure results in perioperative outcomes similar to those achieved with conventional laparoscopic partial nephrectomy done by an experienced surgeon. Robot-assisted partial nephrectomy likely improves surgeon and patient accessibility to minimally invasive nephron sparing surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Diffusion of surgical innovation among patients with kidney cancer

PubMed Central

Miller, David C.; Saigal, Christopher S.; Banerjee, Mousumi; Hanley, Jan; Litwin, Mark S.

2009-01-01

Background Despite their potential benefits to patients with kidney cancer, the adoption of partial nephrectomy and laparoscopy has been gradual and asymmetric. To clarify whether this trend reflects differences in kidney cancer patients or differences in surgeon practice styles, we compared the magnitude of surgeon-attributable variance in the use of partial nephrectomy and laparoscopic radical nephrectomy with that attributable to patient and tumor characteristics. Methods Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified a cohort of 5,483 Medicare beneficiaries treated surgically for kidney cancer between 1997 and 2002. We defined two primary outcomes: (1) use of partial nephrectomy, and (2) use of laparoscopy among patients undergoing radical nephrectomy. Using multilevel models, we estimated surgeon- and patient-level contributions to observed variations in the use of partial nephrectomy and laparoscopic radical nephrectomy. Results Of the 5,483 cases identified, 611(11.1%) underwent partial nephrectomy (43 performed laparoscopically), and 4,872 (88.9%) underwent radical nephrectomy (515 performed laparoscopically). After adjusting for patient demographics, comorbidity, tumor size and surgeon volume, the surgeon-attributable variance was 18.1% for partial nephrectomy and 37.4% for laparoscopy. For both outcomes, the percentage of total variance attributable to surgeon factors was consistently higher than that attributable to patient characteristics. Conclusions For many patients with kidney cancer, the surgery provided depends more on their surgeon’s practice style than on the characteristics of the patient and his or her disease. Consequently, dismantling barriers to surgeon adoption of partial nephrectomy and laparoscopy is an important step toward improving the quality of care for patients with early-stage kidney cancer. PMID:18330868

Robotic-assisted laparoscopic partial nephrectomy: initial experience in Brazil and a review of the literature.

PubMed

Passerotti, Carlo Camargo; Pessoa, Rodrigo; da Cruz, Jose Arnaldo Shiomi; Okano, Marcelo Takeo; Antunes, Alberto Azoubel; Nesrallah, Adriano Joao; Dall'oglio, Marcos Francisco; Andrade, Enrico; Srougi, Miguel

2012-01-01

Partial nephrectomy has become the standard of care for renal tumors less than 4 cm in diameter. Controversy still exists, however, regarding the best surgical approach, especially when minimally invasive techniques are taken into account. Robotic-assisted laparoscopic partial nephrectomy (RALPN) has emerged as a promising technique that helps surgeons achieve the standards of open partial nephrectomy care while offering a minimally invasive approach. The objective of the present study was to describe our initial experience with robotic-assisted laparoscopic partial nephrectomy and extensively review the pertinent literature. Between August 2009 and February 2010, eight consecutive selected patients with contrast enhancing renal masses observed by CT were submitted to RALPN in a private institution. In addition, we collected information on the patients ' demographics, preoperative tumor characteristics and detailed operative, postoperative and pathological data. In addition, a PubMed search was performed to provide an extensive review of the robotic-assisted laparoscopic partial nephrectomy literature. Seven patients had RALPN on the left or right sides with no intraoperative complications. One patient was electively converted to a robotic-assisted radical nephrectomy. The operative time ranged from 120 to 300 min, estimated blood loss (EBL) ranged from 75 to 400 mL and, in five cases, the warm ischemia time (WIT) ranged from 18 to 32 min. Two patients did not require any clamping. Overall, no transfusions were necessary, and there were no intraoperative complications or adverse postoperative clinical events. All margins were negative, and all patients were disease-free at the 6-month follow-up. Robotic-assisted laparoscopic partial nephrectomy is a feasible and safe approach to small renal cortical masses. Further prospective studies are needed to compare open partial nephrectomy with its minimally invasive counterparts.

Review of robot-assisted partial nephrectomy in modern practice

PubMed Central

Weaver, John; Benway, Brian M.

2015-01-01

Partial nephrectomy (PN) is currently the standard treatment for T1 renal tumors. Minimally invasive PN offers decreased blood loss, shorter length of stay, rapid convalescence, and improved cosmesis. Due to the challenges inherent in laparoscopic partial nephrectomy, its dissemination has been stifled. Robot-assisted partial nephrectomy (RAPN) offers an intuitive platform to perform minimally invasive PN. It is one of the fastest growing robotic procedures among all surgical subspecialties. RAPN continues to improve upon the oncological and functional outcomes of renal tumor extirpative therapy. Herein, we describe the surgical technique, outcomes, and complications of RAPN. PMID:28326257

Robotic surgery and hemostatic agents in partial nephrectomy: a high rate of success without vascular clamping.

PubMed

Morelli, Luca; Morelli, John; Palmeri, Matteo; D'Isidoro, Cristiano; Kauffmann, Emanuele Federico; Tartaglia, Dario; Caprili, Giovanni; Pisano, Roberta; Guadagni, Simone; Di Franco, Gregorio; Di Candio, Giulio; Mosca, Franco

2015-09-01

Robot-assisted partial nephrectomy has been proposed as a technique to overcome technical challenges of laparoscopic partial nephrectomy. We prospectively collected and analyzed data from 31 patients who underwent robotic partial nephrectomy with systematic use of hemostatic agents, between February 2009 and October 2014. Thirty-three renal tumors were treated in 31 patients. There were no conversions to open surgery, intraoperative complications, or blood transfusions. The mean size of the resected tumors was 27 mm (median 20 mm, range 5-40 mm). Twenty-seven of 33 lesions (82%) did not require vascular clamping and therefore were treated in the absence of ischemia. All margins were negative. The high partial nephrectomy success rate without vascular clamping suggests that robotic nephron-sparing surgery with systematic use of hemostatic agents may be a safe, effective method to completely avoid ischemia in the treatment of selected renal masses.

Two-year analysis for predicting renal function and contralateral hypertrophy after robot-assisted partial nephrectomy: A three-dimensional segmentation technology study.

PubMed

Kim, Dae Keun; Jang, Yujin; Lee, Jaeseon; Hong, Helen; Kim, Ki Hong; Shin, Tae Young; Jung, Dae Chul; Choi, Young Deuk; Rha, Koon Ho

2015-12-01

To analyze long-term changes in both kidneys, and to predict renal function and contralateral hypertrophy after robot-assisted partial nephrectomy. A total of 62 patients underwent robot-assisted partial nephrectomy, and renal parenchymal volume was calculated using three-dimensional semi-automatic segmentation technology. Patients were evaluated within 1 month preoperatively, and postoperatively at 6 months, 1 year and continued up to 2-year follow up. Linear regression models were used to identify the factors predicting variables that correlated with estimated glomerular filtration rate changes and contralateral hypertrophy 2 years after robot-assisted partial nephrectomy. The median global estimated glomerular filtration rate changes were -10.4%, -11.9%, and -2.4% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The ipsilateral kidney median parenchymal volume changes were -24%, -24.4%, and -21% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The contralateral renal volume changes were 2.3%, 9.6% and 12.9%, respectively. On multivariable linear analysis, preoperative estimated glomerular filtration rate was the best predictive factor for global estimated glomerular filtration rate change on 2 years post-robot-assisted partial nephrectomy (B -0.452; 95% confidence interval -0.84 to -0.14; P = 0.021), whereas the parenchymal volume loss rate (B -0.43; 95% confidence interval -0.89 to -0.15; P = 0.017) and tumor size (B 5.154; 95% confidence interval -0.11 to 9.98; P = 0.041) were the significant predictive factors for the degree of contralateral renal hypertrophy on 2 years post-robot-assisted partial nephrectomy. Preoperative estimated glomerular filtration rate significantly affects post-robot-assisted partial nephrectomy renal function. Renal mass size and renal parenchyma volume loss correlates with compensatory hypertrophy of the contralateral kidney. Contralateral hypertrophy of the renal parenchyma compensates for the functional loss of the ipsilateral kidney. © 2015 The Japanese Urological Association.

Partial nephrectomy in a patient with dwarfism.

PubMed

Farber, Nicholas J; Dubin, Justin; Parihar, Jaspreet; Han, Chris; Lasser, Michael S

2016-08-01

We describe the case of a 50-year-old male with achondroplastic dwarfism who presents with a renal mass in his left kidney concerning for renal cell carcinoma. The patient successfully underwent a robotic partial nephrectomy, which revealed a T1a renal cell carcinoma. The tumor was excised successfully without any intraoperative complications demonstrating that a robotic partial nephrectomy is technically both safe and effective in patients with achondroplastic dwarfism.

Comparative outcomes and assessment of trifecta in 500 robotic and laparoscopic partial nephrectomy cases: a single surgeon experience.

PubMed

Khalifeh, Ali; Autorino, Riccardo; Hillyer, Shahab P; Laydner, Humberto; Eyraud, Remi; Panumatrassamee, Kamol; Long, Jean-Alexandre; Kaouk, Jihad H

2013-04-01

We report a comparative analysis of a large series of laparoscopic and robotic partial nephrectomies performed by a high volume single surgeon at a tertiary care institution. We retrospectively reviewed the medical charts of 500 patients treated with minimally invasive partial nephrectomy by a single surgeon between March 2002 and February 2012. Demographic and perioperative data were collected and statistically analyzed. R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in mm, anterior/posterior and location relative to polar lines) nephrometry score was used to score tumors. Those scored as moderate and high complexity were designated as complex. Trifecta was defined as a combination of warm ischemia time less than 25 minutes, negative surgical margins and no perioperative complications. Two groups were identified, including 261 patients with robotic and 231 with laparoscopic partial nephrectomy. Demographics were similar in the groups. The robotic group was significantly more morbid (Charlson comorbidity index 3.75 vs 1.26), included more complex tumors (R.E.N.A.L. score 5.98 vs 7.2), and had lower operative (169.9 vs 191.7 minutes) and warm ischemia (17.9 vs 25.2 minutes) time, intraoperative (2.6% vs 5.6%, each p <0.001) and postoperative (24.53% vs 32.03%, p = 0.004) complications, and positive margin rate (2.9% vs 5.6%, p <0.001). Thus, a higher overall trifecta rate was observed for robotic partial nephrectomy (58.7% vs 31.6%, p <0.001). The laparoscopic group had longer followup (3.43 vs 1.51 years, p <0.001) and no significant difference in postoperative changes in renal function. Main study limitations were the retrospective nature, arbitrary definition of trifecta and shorter followup in the RPN group. Our large comparative analysis shows that robotic partial nephrectomy offers a wider range of indications, better operative outcomes and lower perioperative morbidity than laparoscopic partial nephrectomy. Overall, the quest for trifecta seems to be better accomplished by robotic partial nephrectomy, which is likely to become the new standard for minimally invasive partial nephrectomy. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Successful Embolization of a Renal Artery Pseudoaneurysm with Arteriovenous Fistula and Extravasations Using Onyx After Partial Nephrectomy for Renal Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zelenak, Kamil, E-mail: zelenak@mfn.s; Sopilko, Igor; Svihra, Jan

2009-01-15

Partial nephrectomy can be associated with vascular complications. Computed tomography (CT) with CT angiography is ideal for noninvasive imaging of this process. The treatment of choice is selective embolization. Successful transcatheter embolization of right renal subsegmental artery pseudoaneurysm with arteriovenous fistula and extravasations using Onyx was performed in a 66-year-old woman with macrohematuria 12 days after partial nephrectomy for renal cell carcinoma.

Osteopontin and splice variant expression level in human malignant glioma: radiobiologic effects and prognosis after radiotherapy.

PubMed

Güttler, Antje; Giebler, Maria; Cuno, Peter; Wichmann, Henri; Keßler, Jacqueline; Ostheimer, Christian; Söling, Ariane; Strauss, Christian; Illert, Jörg; Kappler, Matthias; Vordermark, Dirk; Bache, Matthias

2013-09-01

We investigated the role of the hypoxia-associated secreted glycoprotein osteopontin (OPN) in the response of malignant glioma to radiotherapy by characterizing OPN and its splice variants in vitro and in patient material. The effect of siRNA knockdown of OPN splice variants on cellular and radiobiologic behavior was analyzed in U251MG cells using OpnS siRNA (inhibition of all OPN splice variants) and OpnAC siRNA (knockdown only of OPNa and OPNc). OPN and splice variant mRNA levels were quantified in archival material of 41 glioblastoma tumor samples. Plasma OPN was prospectively measured in 33 malignant glioma patients. Inhibition of OPNa and OPNc (OpnAC) reduced clonogenic survival in U251MG cells but did not affect proliferation, migration or apoptosis. Knockdown of all OPN splice variants (OpnS) resulted in an even stronger inhibition of clonogenic survival, while cell proliferation and migration were reduced and rate of apoptosis was increased. Additional irradiation had additive effects with both siRNAs. Plasma OPN increased continuously in malignant glioma patients and was associated with poor survival. OPNb is partially able to compensate the effects of OPNa and OPNc knockdown in U251MG cells. High OPN plasma levels at the end of radiotherapy are associated with poor survival. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

When Partial Nephrectomy is Unsuccessful: Understanding the Reasons for Conversion from Robotic Partial to Radical Nephrectomy at a Tertiary Referral Center.

PubMed

Kara, Önder; Maurice, Matthew J; Mouracade, Pascal; Malkoç, Ercan; Dagenais, Julien; Nelson, Ryan J; Chavali, Jaya Sai S; Stein, Robert J; Fergany, Amr; Kaouk, Jihad H

2017-07-01

We sought to identify the preoperative factors associated with conversion from robotic partial nephrectomy to radical nephrectomy. We report the incidence of this event. Using our institutional review board approved database, we abstracted data on 1,023 robotic partial nephrectomies performed at our center between 2010 and 2015. Standard and converted cases were compared in terms of patients and tumor characteristics, and perioperative, functional and oncologic outcomes. Logistic regression analysis was done to identify predictors of radical conversion. The overall conversion rate was 3.1% (32 of 1,023 cases). The most common reasons for conversion were tumor involvement of hilar structures (8 cases or 25%), failure to achieve negative margins on frozen section (7 or 21.8%), suspicion of advanced disease (5 or 15.6%) and failure to progress (5 or 15.6%). Patients requiring conversion were older and had a higher Charlson score (both p <0.01), including an increased prevalence of chronic kidney disease (p = 0.02). Increasing tumor size (5 vs 3.1 cm, p <0.01) and R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and hilar location) score (9 vs 8, p <0.01) were also associated with an increased risk of conversion. Worse baseline renal function (OR 0.98, 95% CI 0.96-0.99, p = 0.04), large tumor size (OR 1.44, 95% CI 1.22-1.7, p <0.01) and increasing R.E.N.A.L. score (p = 0.02) were independent predictors of conversion. Compared to converted cases, at latest followup standard robotic partial nephrectomy cases had similar short-term oncologic outcomes but better renal functional preservation (p <0.01). At a high volume center the rate of robotic partial nephrectomy conversion to radical nephrectomy was 3.1%, including 2.2% of preoperatively anticipated nephrectomy cases. Increasing tumor size and complexity, and poor preoperative renal function are the main predictors of conversion. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Value of Nephrometry Score Constituents on Perioperative Outcomes and Split Renal Function in Patients Undergoing Minimally Invasive Partial Nephrectomy.

PubMed

Watts, Kara L; Ghosh, Propa; Stein, Solomon; Ghavamian, Reza

2017-01-01

To assess the relationship between individual nephrometry score (NS) constituents (RENAL) on perioperative outcomes and renal function of the surgical kidney in patients undergoing laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy. Two hundred forty-five patients who underwent laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Each renal mass' NS was calculated from preoperative computed tomography imaging. Multivariate regression analysis was used to evaluate the effect of NS variables on perioperative outcomes and change in overall renal function (as estimated by glomerular filtration rate) from preoperative to 1-year postoperative. A cohort analysis assessed the effect of NS variables on change in split renal function of the surgical kidney from pre- to postoperative based on nuclear medicine renal scintigraphy. Tumor radius (R), endophytic nature (E), and nearness to collecting system (N) variables significantly and incrementally predicted a longer operative time and warm ischemia time. Overall renal function based on glomerular filtration rate was not affected by any NS variable. However, percent function of the surgical kidney by renal scintigraphy significantly decreased postoperatively as R and E values increased. R, E, and N were associated with significant changes in warm ischemia time and operative time. R and E were associated with a significant decrease in split renal function of the surgical kidney at 1 year after surgery but not with overall renal function. R, E, and N are the NS constituents most relevant to perioperative outcomes and postoperative differential renal function after partial nephrectomy. Copyright © 2016. Published by Elsevier Inc.

Zero ischemia robotic-assisted partial nephrectomy in Alberta: Initial results of a novel approach.

PubMed

Forbes, Ellen; Cheung, Douglas; Kinnaird, Adam; Martin, Blair St

2015-01-01

Partial nephrectomy remains the standard of care in early stage, organ-confined renal tumours. Recent evidence suggests that minimally invasive surgery can proceed without segmental vessel clamping. In this study, we review our experience at a Canadian centre with zero ischemia robotic-assisted partial nephrectomy (RAPN). A retrospective chart review of zero ischemia RAPN was performed. All surgeries were consecutive partial nephrectomies performed by the same surgeon at a tertiary care centre in Northern Alberta. The mean follow-up period was 28 months. These outcomes were compared against the current standards for zero ischemia (as outlined by the University of Southern California Institute of Urology [USC]). We included 21 patients who underwent zero ischemia RAPN between January 2012 and June 2013. Baseline data were similar to contemporary studies. Twelve (57.1%) required no vascular clamping, 7 (33.3%) required clamping of a single segmental artery, and 2 (9.5%) required clamping of two segmental arteries. We achieved an average estimated blood loss of 158 cc, with a 9.2% average increase in creatinine postoperatively. Operating time and duration of hospital stay were short at 153 minutes and 2.2 days, respectively. Zero ischemia partial nephrectomy was a viable option at our institution with favourable results in terms of intra-operative blood loss and postoperative creatinine change compared to results from contemporary standard zero ischemia studies (USC). To our knowledge, this is the first study to review an initial experience with the zero ischemia protocol in robotic-assisted partial nephrectomies at a Canadian hospital.

Prospective study on laser-assisted laparascopic partial nephrectomy

NASA Astrophysics Data System (ADS)

Sroka, Ronald; Hennig, Georg; Zilinberg, Katja; Khoder, Wael Y.

2012-02-01

Introduction: Developments in laparoscopic partial nephrectomy (LPN) opened a demand for surgical tools compatible with laparoscopic manipulations to make laser assisted technique safe, feasible and reproducible. Warm ischemia and bleeding during laparoscopic partial nephrectomy place technical constraints on surgeons. Therefore it was the aim to develop a safe and effective laser assisted partial nephrectomy technique without need for ischemia. Patients and methods: A diode laser emitting light at 1318nm in cw mode was coupled into a bare fibre (core diameter 600 μm) thus able to transfer up to 100W to the tissue. After dry lab experience, a total of 10 patients suffering from kidney malformations underwent laparoscopic/retroperitoneoscopic partial nephrectomy. Clinically, postoperative renal function and serum c-reactive protein (CRP) were monitored. Laser induced coagulation depth and effects on resection margins were evaluated. Demographic, clinical and follow-up data are presented. Using a commercial available fibre guidance instrument for lanringeal intervention, the demands on an innovative laser fibre guidance instrument for the laser assisted laparoscopic partial nephrectomy (LLPN) are summarized. Results: Overall, all laparascopic intervention were succesfull and could be performed without conversion to open surgery. Mean operative time and mean blood loss were comparable to conventional open and laparascopic approaches. Laser assisted resection of the kidney tissue took max 15min. After extirpation of the tumours all patients showed clinical favourable outcome during follow up period. Tumour sizes were measured to be up 5cm in diameter. The depth of the coagulation on the removed tissue ranged between <1 to 2mm without effect on histopathological evaluation of tumours or resection margin. As the surface of the remaining kidney surface was laser assisted coagulated after removal. The sealing of the surface was induced by a slightly larger coagulation margin, but could not measured so far. Based on this experiences a simple and easy to use instrument described serving also for suction and rinsing. Conclusion: This prospective in-vivo feasibility study shows that laser assisted partial nephrectomy seems to be a safe and promising medical technique which could be provided either during open surgery as well as laparascopically. This application showed good haemostasis and minimal parenchymal damage. Further investigations and development are needed for on-line detection of the remain coagulation margin. An optimised treatment equipment will support the applicability of laser assisted laparoscopic partial nephrectomy.

Separation Options for Phosphorylated Osteopontin from Transgenic Microalgae Chlamydomonas reinhardtii

PubMed Central

Ravi, Ayswarya; Guo, Shengchun; Rasala, Beth; Tran, Miller; Mayfield, Stephen; Nikolov, Zivko L.

2018-01-01

Correct folding and post-translational modifications are vital for therapeutic proteins to elicit their biological functions. Osteopontin (OPN), a bone regenerative protein present in a range of mammalian cells, is an acidic phosphoprotein with multiple potential phosphorylation sites. In this study, the ability of unicellular microalgae, Chlamydomonas reinhardtii, to produce phosphorylated recombinant OPN in its chloroplast is investigated. This study further explores the impact of phosphorylation and expression from a “plant-like” algae on separation of OPN. Chromatography resins ceramic hydroxyapatite (CHT) and Gallium-immobilized metal affinity chromatography (Ga-IMAC) were assessed for their binding specificity to phosphoproteins. Non-phosphorylated recombinant OPN expressed in E. coli was used to compare the specificity of interaction of the resins to phosphorylated OPN. We observed that CHT binds OPN by multimodal interactions and was better able to distinguish phosphorylated proteins in the presence of 250 mM NaCl. Ga-IMAC interaction with OPN was not selective to phosphorylation, irrespective of salt, as the resin bound OPN from both algal and bacterial sources. Anion exchange chromatography proved an efficient capture method to partially separate major phosphorylated host cell protein impurities such as Rubisco from OPN. PMID:29462927

Delayed Partial Nephrectomy for Hydronephrosis After Renal Trauma.

PubMed

Setia, Shaan; Jackson, Jessica Nicole; Herndon, C D Anthony; Corbett, Sean T

2017-03-01

Delayed sequelae following conservative management of renal trauma in the pediatric population are uncommon. Reports of delayed operations to manage these sequelae are even less common. Here we present the case of a 16-year-old male patient who had delayed development of upper urinary tract obstruction with recurrent infections following high-grade renal trauma managed conservatively. Ultimately, he required a robotic-assisted partial nephrectomy 2 years after initial nonoperative management. This is unique as no prior studies to our knowledge have described delayed hydronephrosis and delayed partial nephrectomy over a year following renal trauma. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of near infrared fluorescence during robot-assisted laparoscopic partial nephrectomy.

PubMed

Cornejo-Dávila, V; Nazmy, M; Kella, N; Palmeros-Rodríguez, M A; Morales-Montor, J G; Pacheco-Gahbler, C

2016-04-01

Partial nephrectomy is the treatment of choice for T1a tumours. The open approach is still the standard method. Robot-assisted laparoscopic surgery offers advantages that are applicable to partial nephrectomy, such as the use of the Firefly® system with near-infrared fluorescence. To demonstrate the implementation of fluorescence in nephron-sparing surgery. This case concerned a 37-year-old female smoker, with obesity. The patient had a right kidney tumour measuring 31 mm, which was found using tomography. She therefore underwent robot-assisted laparoscopic partial nephrectomy, with a warm ischaemia time of 22 minutes and the use of fluorescence with the Firefly® system to guide the resection. There were no complications. The tumour was a pT1aN0M0 renal cell carcinoma, with negative margins. Robot-assisted renal laparoscopic surgery is employed for nephron-sparing surgery, with good oncological and functional results. The combination of the Firefly® technology and intraoperative ultrasound can more accurately delimit the extent of the lesion, increase the negative margins and decrease the ischaemia time. Near-infrared fluorescence in robot-assisted partial nephrectomy is useful for guiding the tumour resection and can potentially improve the oncological and functional results. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

The natural history of renal function after surgical management of renal cell carcinoma: Results from the Canadian Kidney Cancer Information System.

PubMed

Mason, Ross; Kapoor, Anil; Liu, Zhihui; Saarela, Olli; Tanguay, Simon; Jewett, Michael; Finelli, Antonio; Lacombe, Louis; Kawakami, Jun; Moore, Ronald; Morash, Christopher; Black, Peter; Rendon, Ricardo A

2016-11-01

Patients who undergo surgical management of renal cell carcinoma (RCC) are at risk for chronic kidney disease and its sequelae. This study describes the natural history of renal function after radical and partial nephrectomy and explores factors associated with postoperative decline in renal function. This is a multi-institutional cohort study of patients in the Canadian Kidney Cancer Information System who underwent partial or radical nephrectomy for RCC. Estimated glomerular filtration rate (eGFR) and stage of chronic kidney disease were determined preoperatively and at 3, 12, and 24 months postoperatively. Linear regression was used to determine the association between postoperative eGFR and type of surgery (radical vs. partial), duration of ischemia, ischemia type (warm vs. cold), and tumor size. With a median follow-up of 26 months, 1,379 patients were identified from the Canadian Kidney Cancer Information System database including 665 and 714 who underwent partial and radical nephrectomy, respectively. Patients undergoing radical nephrectomy had a lower eGFR (mean = 19ml/min/1.73m 2 lower) at 3, 12, and 24 months postoperatively (P<0.001). Decline in renal function occurred early and remained stable throughout follow-up. A lower preoperative eGFR and increasing age were also associated with a lower postoperative eGFR (P<0.01). Ischemia type and duration were not predictive of postoperative decline in eGFR (P>0.05). Severe renal failure (eGFR<30ml/min/1.73m 2 ) developed postoperatively in 12.5% and 4.1% of radical and partial nephrectomy patients, respectively (P<0.001). After the initial postoperative decline, renal function remains stable in patients undergoing surgery for RCC. Patients undergoing radical nephrectomy have a greater long-term reduction in renal function compared with those undergoing partial nephrectomy. Ischemia duration and type are not predictive of postoperative renal function when adhering to generally short ischemia durations. Copyright © 2016 Elsevier Inc. All rights reserved.

[Cost comparison of open and robot-assisted partial nephrectomy in treatment of renal tumor].

PubMed

Abd El Fattah, V; Chevrot, A; Meusy, A; Mercier, G; Wagner, L; Soustelle, L; Boukaram, M; Thuret, R; Costa, P; Droupy, S

2016-04-01

Robot-assisted partial nephrectomy rapidly took on among urologists, even though studies showing its superiority over other techniques are still scarce and its costs hard to evaluate, especially in the French medical system. To evaluate the cost overrun of robot-assisted partial nephrectomy compared to that of open partial nephrectomy. From January 2010 to December 2013, 77 patients underwent a partial nephrectomy, 46 of which by robot-assisted laparoscopy and the remaining 31 by lombotomy. The two groups were similar in composition. Economic data regarding the staff, the consumables and the premises involved have been analyzed. Costs are significantly higher in the NPR group (9253.21 euros vs. 7448.42 euros) due to higher consumable expenses as well as the costs pertaining to the amortization and maintenance of the robot. Yet, that difference tends to diminish as the duration of the experiment increases. No significant difference was found in warm ischemia times, operation duration and renal function a month after the operation. On the other hand, patients from the NPR group spent a significantly smaller amount of time in recovery room (159 minutes vs. 205 minutes, P=0.004), presented fewer complications and were discharged faster (6.1 days vs. 8.1 days, P=0.04). To be profitable for the hospital in the French GHS system, robot-assisted partial nephrectomy must take place in a complex where at least 300 robot-assisted interventions are performed annually, in the framework of a hospitalization lasting four days or less, the use of a single needle holder and no systematic use of a haemostatic agent. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Robotic partial nephrectomy for complex renal tumors: surgical technique.

PubMed

Rogers, Craig G; Singh, Amar; Blatt, Adam M; Linehan, W Marston; Pinto, Peter A

2008-03-01

Laparoscopic partial nephrectomy requires advanced training to accomplish tumor resection and renal reconstruction while minimizing warm ischemia times. Complex renal tumors add an additional challenge to a minimally invasive approach to nephron-sparing surgery. We describe our technique, illustrated with video, of robotic partial nephrectomy for complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance was used to resect 14 tumors in eight patients (mean age: 50.3 yr; range: 30-68 yr). Three patients had hereditary kidney cancer. All patients had complex tumor features, including hilar tumors (n=5), endophytic tumors (n=4), and/or multiple tumors (n=3). Robotic partial nephrectomy procedures were performed successfully without complications. Hilar clamping was used with a mean warm ischemia time of 31 min (range: 24-45 min). Mean blood loss was 230 ml (range: 100-450 ml). Histopathology confirmed clear-cell renal cell carcinoma (n=3), hybrid oncocytic tumor (n=2), chromophobe renal cell carcinoma (n=2), and oncocytoma (n=1). All patients had negative surgical margins. Mean index tumor size was 3.6 cm (range: 2.6-6.4 cm). Mean hospital stay was 2.6 d. At 3-mo follow-up, no patients experienced a statistically significant change in serum creatinine or estimated glomerular filtration rate and there was no evidence of tumor recurrence. Robotic partial nephrectomy is safe and feasible for select patients with complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance may facilitate a minimally invasive, nephron-sparing approach for select patients with complex renal tumors who might otherwise require open surgery or total nephrectomy.

Drain placement can be safely omitted after the majority of robotic partial nephrectomies.

PubMed

Abaza, Ronney; Prall, David

2013-03-01

Drain placement after partial nephrectomy is considered standard but it is based on routine and not on evidence. With experience we performed robotic partial nephrectomy and routinely omitted a drain even with significant collecting system violation. We have rarely used drains after robotic partial nephrectomy for several years, and we report our outcomes. We reviewed a single surgeon, prospective database of all robotic partial nephrectomies from February 2008 to March 2012, including the characteristics of those with and without a drain. The 150 patients underwent a total of 160 robotic partial nephrectomy procedures with a drain used in 11 patients and omitted in 93%. Mean patient age was 57 years (range 22 to 89), mean American Society of Anesthesiologists score was 2.8 (range 2 to 4) and mean body mass index was 32 kg/m(2) (range 18 to 54). Values were similar in patients with and without a drain. In patients without a drain and in those with a drain mean tumor size was 3.5 cm (range 1.0 to 11.0) and 4.6 cm (range 1.1 to 8.6), and mean R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines, hilar tumor touching main renal artery or vein) nephrometry score was 7.8 (range 4 to 12) and 8.8 (range 6 to 11), respectively. Collecting system violation occurred in 88 patients (59%), including 78 without a drain. Two patients (1.3%) required transfusion with no intervention for bleeding. All except 5 patients (97%) were discharged home on postoperative day 1 with all drains removed before discharge. In 2 patients (1.3%) without a drain small urinomas without infection developed more than 2 weeks postoperatively, which were treated with a week of Foley catheter drainage and percutaneous drainage, respectively. Drain placement after robotic partial nephrectomy can be routinely omitted with a low rate of urine leaks, which can be managed safely when they rarely occur. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Comparing Zero Ischemia Laparoscopic Radio Frequency Ablation Assisted Tumor Enucleation and Laparoscopic Partial Nephrectomy for Clinical T1a Renal Tumor: A Randomized Clinical Trial.

PubMed

Huang, Jiwei; Zhang, Jin; Wang, Yanqing; Kong, Wen; Xue, Wei; Liu, Dongming; Chen, YongHui; Huang, Yiran

2016-06-01

We evaluated the functional outcome, safety and efficacy of zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation compared with conventional laparoscopic partial nephrectomy. A prospective randomized controlled trial was conducted from April 2013 to March 2015 in patients with cT1a renal tumor scheduled for laparoscopic nephron sparing surgery. All patients were followed for at least 12 months. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation group underwent tumor enucleation after radio frequency ablation without hilar clamping. The primary outcome was the change in glomerular filtration rate of the affected kidney by renal scintigraphy at 12 months. Secondary outcomes included changes in estimated glomerular filtration rate, estimated blood loss, operative time, hospital stay, postoperative complications and oncologic outcomes. The Pearson chi-square or Fisher exact, Student t-test and Wilcoxon rank sum tests were used. The trial ultimately enrolled 89 patients, of whom 44 were randomized to the laparoscopic radio frequency ablation assisted tumor enucleation group and 45 to the laparoscopic partial nephrectomy group. In the laparoscopic partial nephrectomy group 1 case was converted to radical nephrectomy. Compared with the laparoscopic partial nephrectomy group, patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a smaller decrease in glomerular filtration rate of the affected kidney at 3 months (10.2% vs 20.5%, p=0.001) and 12 months (7.6% vs 16.2%, p=0.002). Patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a shorter operative time (p=0.002), lower estimated blood loss (p <0.001) and a shorter hospital stay (p=0.029) but similar postoperative complications (p=1.000). There were no positive margins or local recurrence in this study. Zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation enables tumor excision with better renal function preservation compared to conventional laparoscopic partial nephrectomy. Less blood loss and a shorter operative time were achieved with similar postoperative complication rates. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bone Alkaline Phosphatase and Tartrate-Resistant Acid Phosphatase: Potential Co-regulators of Bone Mineralization.

PubMed

Halling Linder, Cecilia; Ek-Rylander, Barbro; Krumpel, Michael; Norgård, Maria; Narisawa, Sonoko; Millán, José Luis; Andersson, Göran; Magnusson, Per

2017-07-01

Phosphorylated osteopontin (OPN) inhibits hydroxyapatite crystal formation and growth, and bone alkaline phosphatase (BALP) promotes extracellular mineralization via the release of inorganic phosphate from the mineralization inhibitor inorganic pyrophosphate (PPi). Tartrate-resistant acid phosphatase (TRAP), produced by osteoclasts, osteoblasts, and osteocytes, exhibits potent phosphatase activity towards OPN; however, its potential capacity as a regulator of mineralization has not previously been addressed. We compared the efficiency of BALP and TRAP towards the endogenous substrates for BALP, i.e., PPi and pyridoxal 5'-phosphate (PLP), and their impact on mineralization in vitro via dephosphorylation of bovine milk OPN. TRAP showed higher phosphatase activity towards phosphorylated OPN and PPi compared to BALP, whereas the activity of TRAP and BALP towards PLP was comparable. Bovine milk OPN could be completely dephosphorylated by TRAP, liberating all its 28 phosphates, whereas BALP dephosphorylated at most 10 phosphates. OPN, dephosphorylated by either BALP or TRAP, showed a partially or completely attenuated phosphorylation-dependent inhibitory capacity, respectively, compared to native OPN on the formation of mineralized nodules. Thus, there are phosphorylations in OPN important for inhibition of mineralization that are removed by TRAP but not by BALP. In conclusion, our data indicate that both BALP and TRAP can alleviate the inhibitory effect of OPN on mineralization, suggesting a potential role for TRAP in skeletal mineralization. Further studies are warranted to explore the possible physiological relevance of TRAP in bone mineralization.

Transperitoneal approach versus retroperitoneal approach: a meta-analysis of laparoscopic partial nephrectomy for renal cell carcinoma.

PubMed

Ren, Tong; Liu, Yan; Zhao, Xiaowen; Ni, Shaobin; Zhang, Cheng; Guo, Changgang; Ren, Minghua

2014-01-01

To compare the efficiency and safety of the transperitoneal approaches with retroperitoneal approaches in laparoscopic partial nephrectomy for renal cell carcinoma and provide evidence-based medicine support for clinical treatment. A systematic computer search of PUBMED, EMBASE, and the Cochrane Library was executed to identify retrospective observational and prospective randomized controlled trials studies that compared the outcomes of the two approaches in laparoscopic partial nephrectomy. Two reviewers independently screened, extracted, and evaluated the included studies and executed statistical analysis by using software STATA 12.0. Outcomes of interest included perioperative and postoperative variables, surgical complications and oncological variables. There were 8 studies assessed transperitoneal laparoscopic partial nephrectomy (TLPN) versus retroperitoneal laparoscopic partial nephrectomy (RLPN) were included. RLPN had a shorter operating time (SMD = 1.001,95%confidence interval[CI] 0.609-1.393,P<0.001), a lower estimated blood loss (SMD = 0.403,95%CI 0.015-0.791,P = 0.042) and a shorter length of hospital stay (WMD = 0.936 DAYS,95%CI 0.609-1.263,P<0.001) than TLPN. There were no significant differences between the transperitoneal and retroperitoneal approaches in other outcomes of interest. This meta-analysis indicates that, in appropriately selected patients, especially patients with intraperitoneal procedures history or posteriorly located renal tumors, the RLPN can shorten the operation time, reduce the estimated blood loss and shorten the length of hospital stay. RLPN may be equally safe and be faster compared with the TLPN.

Renal functional and perioperative outcomes of off-clamp versus clamped robot-assisted partial nephrectomy: matched cohort study.

PubMed

Tanagho, Youssef S; Bhayani, Sam B; Sandhu, Gurdarshan S; Vaughn, Nicholas P; Nepple, Kenneth G; Figenshau, R Sherburne

2012-10-01

To evaluate the potential benefit of performing off-clamp robot-assisted partial nephrectomy as it relates to renal functional outcomes, while assessing the safety profile of this unconventional surgical approach. Twenty-nine patients who underwent off-clamp robot-assisted partial nephrectomy for suspected renal cell carcinoma at Washington University between March 2008 and September 2011 (group 1) were matched to 29 patients with identical nephrometry scores and comparable baseline renal function who underwent robot-assisted partial nephrectomy with hilar clamping during the same period (group 2). The matched cohorts' perioperative and renal functional outcomes were compared at a mean 9-month follow-up. Mean estimated blood loss was 146.4 mL in group 1, versus 103.9 mL in group 2 (P = .039). Mean hilar clamp time was 0 minutes in group 1 and 14.7 minutes in group 2. No perioperative complications were encountered in group 1; 1 Clavien-2 complication (3.4%) occurred in group 2 (P = 1.000). At 9-month follow-up, mean estimated glomerular filtration rate in group 1 was 79.9 versus 84.8 mL/min/1.73 m(2) preoperatively (P = .013); mean estimated glomerular filtration rate in group 2 was 74.1 versus 85.8 mL/min/1.73 m(2) preoperatively (P < .001). Hence, estimated glomerular filtration rate declined by a mean of 4.9 mL/min/1.73 m(2) in group 1 versus 11.7 mL/min/1.73 m(2) in group 2 (P = .033). Off-clamp robot-assisted partial nephrectomy is associated with a favorable morbidity profile and relatively greater renal functional preservation compared to clamped robot-assisted partial nephrectomy. Nevertheless, the benefit is small in renal functional terms and may have very limited clinical relevance. Copyright © 2012 Elsevier Inc. All rights reserved.

Yonsei nomogram: A predictive model of new-onset chronic kidney disease after on-clamp partial nephrectomy in patients with T1 renal tumors.

PubMed

Abdel Raheem, Ali; Shin, Tae Young; Chang, Ki Don; Santok, Glen Denmer R; Alenzi, Mohamed Jayed; Yoon, Young Eun; Ham, Won Sik; Han, Woong Kyu; Choi, Young Deuk; Rha, Koon Ho

2018-06-19

To develop a predictive nomogram for chronic kidney disease-free survival probability in the long term after partial nephrectomy. A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end-points were to identify independent risk factors for new-onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease-free survival probability after partial nephrectomy. The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new-onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease-free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new-onset chronic kidney disease. The C-index for chronic kidney disease-free survival was 0.853 (95% confidence interval 0.815-0.895). We developed a novel nomogram for predicting the 5-year chronic kidney disease-free survival probability after on-clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision-making and follow-up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered. © 2018 The Japanese Urological Association.

Visual Enhancement of Laparoscopic Partial Nephrectomy With 3-Charge Coupled Device Camera: Assessing Intraoperative Tissue Perfusion and Vascular Anatomy by Visible Hemoglobin Spectral Response

DTIC Science & Technology

2010-10-01

open nephron spanng surgery a single institution expenence. J Ural 2005; 174: 855 21 Bhayan• SB, Aha KH Pmto PA et al Laparoscopic partial...noninvasively assess laparoscopic intraoperative changes in renal tissue perfusion during and after warm ischemia. Materials and Methods: We analyzed select...TITLE AND SUBTITLE Visual Enhancement of Laparoscopic Partial Nephrectomy With 3-Charge Coupled Device Camera: Assessing Intraoperative Tissue

A comparative cost analysis of robot-assisted versus traditional laparoscopic partial nephrectomy.

PubMed

Hyams, Elias; Pierorazio, Philip; Mullins, Jeffrey K; Ward, Maryann; Allaf, Mohamad

2012-07-01

Robot-assisted laparoscopic partial nephrectomy (RALPN) is supplanting traditional laparoscopic partial nephrectomy (LPN) as the technique of choice for minimally invasive nephron-sparing surgery. This evolution has resulted from potential clinical benefits, as well as proliferation of robotic systems and patient demand for robot-assisted surgery. We sought to quantify the costs associated with the use of robotics for minimally invasive partial nephrectomy. A cost analysis was performed for 20 consecutive robot-assisted partial nephrectomy (RPN) and LPN patients at our institution from 2009 to 2010. Data included actual perioperative and hospitalization costs as well as professional fees. Capital costs were estimated using purchase costs and amortization of two robotic systems from 2001 to 2009, as well as maintenance contract costs. The estimated cost/case was obtained using total robotic surgical volume during this period. Total estimated costs were compared between groups. A separate analysis was performed assuming "ideal" robotic utilization during a comparable period. RALPN had a cost premium of +$1066/case compared with LPN, assuming actual robot utilization from 2001 to 2009. Assuming "ideal" utilization during a comparable period, this premium decreased to +$334; capital costs per case decreased from $1907 to $1175. Tumor size, operative time, and length of stay were comparable between groups. RALPN is associated with a small to moderate cost premium depending on assumptions regarding robotic surgical volume. Saturated utilization of robotic systems decreases attributable capital costs and makes comparison with laparoscopy more favorable. Purported clinical benefits of RPN (eg, decreased warm ischemia time, increased utilization of nephron-sparing surgery) need further study, because these may have cost implications.

Drain placement can safely be omitted for open partial nephrectomy: Results from a prospective randomized trial.

PubMed

Kriegmair, Maximilian C; Mandel, Philipp; Krombach, Patrick; Dönmez, Hasan; John, Axel; Häcker, Axel; Michel, Maurice S

2016-05-01

To examine the benefit of drain placement during open partial nephrectomy. Overall, 106 patients treated with open partial nephrectomy were enrolled in a prospective randomized trial. Based on the randomization, a drain was placed or omitted. Complications were assessed according to the Clavien classification. Pain level and requirement for analgesics was evaluated according to a customized pattern. There was no significant difference in the two groups regarding age, body mass index, American Society of Anesthesiologists score, tumor size and nephrometry (preoperative aspects and dimensions used for an anatomical classification). In terms of overall and drain-related complications, no advantage of placing a drain could be proven (P = 0.249). Patients with a drain suffered from a significantly higher pain level (P = 0.01) and showed prolonged mobilization (P < 0.001). There was no difference in bowel movements and requirement of additional analgesics (P = 0.347 and 0.11). The results of the study suggest that drain placement during open partial nephrectomy can safely be omitted, even in cases with violation of the collecting system. © 2016 The Japanese Urological Association.

[A new technique for ensuring negative surgical margins during partial nephrectomy: the ex vivo ultrasound control].

PubMed

Desmonts, A; Tillou, X; Le Gal, S; Secco, M; Orczyk, C; Bensadoun, H; Doerfler, A

2013-10-01

To evaluate the feasibility and the efficiency of intraoperative ex vivo ultrasound of resection margins in patients undergoing partial nephrectomy by urologist. Patients undergoing partial nephrectomy from July 2010 to November 2012 for T1-T2 renal tumors were included in analysis. Tumor margin status was immediately determined by ex vivo ultrasound done by the surgeon himself. Results were compared with margin status on definitive pathological evaluation. A total of 26 men and 15 women with a median age of 61 (30-82) years old were included in analysis. Intraoperative ex vivo ultrasound revealed negative surgical margins in 38 cases and positive margins in two. Final pathological results revealed negative margins in all except one case. Ultrasound sensitivity and specificity were 100% and 97%, respectively. Mean ultrasound duration was 1minute±1. Mean tumor and margin sizes were 3.4±1.8cm and 2.38±1.76mm, respectively. Intraoperative ex vivo ultrasound of resection margins in patients undergoing partial nephrectomy by a urologist seemed to be feasible, efficient and easy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Surgical complications associated with robotic urologic procedures in elderly patients.

PubMed

Cusano, Antonio; Haddock, Peter; Staff, Ilene; Jackson, Max; Abarzua-Cabezas, Fernando; Dorin, Ryan; Meraney, Anoop; Wagner, Joseph; Shichman, Steven; Kesler, Stuart

2015-02-01

Urologic malignancies are often diagnosed at an older age, and are increasingly managed utilizing robotic-assisted surgical techniques. As such, we assessed and compared peri-postoperative complication rates following robotic urologic surgery in elderly and younger patients. A retrospective analysis of IRB-approved databases and electronic medical records identified patients who underwent robotic-assisted urologic surgery between December 2003-September 2013. Patients were grouped according to surgical procedure (partial nephrectomy, radical cystectomy, radical prostatectomy) and age at surgery (≤ 74 or ≥ 75 years old). Associations between age, comorbidities, Charlson comorbidity index (CCI), and patient outcomes were evaluated within each surgery type. 97.5% and 2.5% of patients were ≤ 74 or ≥ 75 years old, respectively. Cystectomies, partial nephrectomies and prostatectomies accounted for 3.5%, 9.5% and 87.1% of surgeries, respectively. Within cystectomy, nephrectomy and prostatectomy groups, 24.4%, 12.5% and 0.6% patients were ≥ 75 years old. Within each surgical type, elderly patients had significantly elevated CCI scores. Length of stay was significantly prolonged in elderly patients undergoing partial nephrectomy or prostatectomy. In elderly cystectomy, partial nephrectomy and prostatectomy patients, 36.7%, 14.3% and 5.9% suffered ≥ 1 Clavien grade 3-5 complication, respectively. Major complications were not significantly different between age groups. A qualitatively similar pattern was observed regarding Clavien grade 1-2 complications. The risks of robotic-assisted urologic surgery in elderly patients are not significantly elevated compared to younger patients.

External Validation of Contact Surface Area as a Predictor of Postoperative Renal Function in Patients Undergoing Partial Nephrectomy.

PubMed

Haifler, Miki; Ristau, Benjamin T; Higgins, Andrew M; Smaldone, Marc C; Kutikov, Alexander; Zisman, Amnon; Uzzo, Robert G

2017-09-20

We sought to externally validate a mathematical formula for tumor contact surface area as a predictor of postoperative renal function in patients undergoing partial nephrectomy for renal cell carcinoma. We queried a prospectively maintained kidney cancer database for patients who underwent partial nephrectomy between 2014 and 2016. Contact surface area was calculated using data obtained from preoperative cross-sectional imaging. The correlation between contact surface area and perioperative variables was examined. The correlation between postoperative renal functional outcomes, contact surface area and the R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and tumor touches main renal artery or vein) nephrometry score was also assessed. A total of 257 patients who underwent partial nephrectomy had sufficient data to enter the study. Median contact surface area was 14.5 cm 2 (IQR 6.2-36) and the median nephrometry score was 9 (IQR 7-10). Spearman correlation analysis showed that contact surface area correlated with estimated blood loss (r s = 0.42, p <0.001), length of stay (r s = 0.18, p = 0.005), and percent and absolute change in the estimated glomerular filtration rate (r s = -0.77 and -0.78, respectively, each p <0.001). On multivariable analysis contact surface area and nephrometry score were independent predictors of the absolute change in the estimated glomerular filtration rate (each p <0.001). ROC curve analysis revealed that contact surface area was a better predictor of a greater than 20% postoperative decline in the estimated glomerular filtration rate compared with the nephrometry score (AUC 0.94 vs 0.80). Contact surface area correlated with the change in postoperative renal function after partial nephrectomy. It can be used in conjunction with the nephrometry score to counsel patients about the risk of renal functional decline after partial nephrectomy. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

R-LESS partial nephrectomy trifecta outcome is inferior to multiport robotic partial nephrectomy: comparative analysis.

PubMed

Komninos, Christos; Shin, Tae Young; Tuliao, Patrick; Yoon, Young Eun; Koo, Kyo Chul; Chang, Chien-Hsiang; Kim, Sang Woon; Ha, Ji Yong; Han, Woong Kyu; Rha, Koon Ho

2014-09-01

Trifecta achievement in partial nephrectomy (PN) is defined as the combination of warm ischemia time ≤ 20 min, negative surgical margins, and no surgical complications. To compare trifecta achievement between robotic, laparoendoscopic, single-site (R-LESS) PN and multiport robotic PN (RPN). Data from 167 patients who underwent RPN from 2006 to 2012 were retrospectively analyzed. Primary outcome measurement was trifecta achievement; secondary outcome was the perioperative and postoperative comparison between groups. The measurements were estimated and analyzed with SPSS v.18 using univariable, multivariable, and subgroup analyses. Eighty-nine patients were treated with RPN and 78 were treated with R-LESS PN. Baseline characteristics of both groups were similar. Trifecta was achieved in 38 patients (42.7%) in the multiport RPN group and 20 patients (25.6%) in the R-LESS PN group (p=0.021). Patients in the R-LESS PN group had longer mean operative time, warm ischemia time, and increased estimated glomerular filtration rate (eGFR) percentage change. No significant differences were found between the two groups in days of hospitalization, blood loss, postoperative eGFR, positive surgical margins, and surgical complications. Patients with increased PADUA and RENAL scores, infiltration of the collecting system, and renal sinus involvement had an increased probability of not achieving the trifecta. In regression analysis, the type of procedure and the tumor size could predict trifecta accomplishment (p=0.019 and 0.043, respectively). The retrospective study, the low number of series, and the controversial definition of trifecta were the main limitations. The trifecta was achieved in significantly more patients who underwent multiport RPN than those who underwent R-LESS PN. R-LESS PN could be an alternative option for patients with decreased tumor size, low PADUA and RENAL scores, and without renal sinus or collecting system involvement. In this study, we looked at the outcomes of patients who had undergone robotic partial nephrectomy. We found that conventional robotic partial nephrectomy is superior to R-LESS partial nephrectomy with regard to the accomplishment of negative margins, reduced warm ischemia time, and minimal surgical complications. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Different methods of hilar clamping during partial nephrectomy: Impact on renal function.

PubMed

Lee, Jeong Woo; Kim, Hwanik; Choo, Minsoo; Park, Yong Hyun; Ku, Ja Hyeon; Kim, Hyeon Hoe; Kwak, Cheol

2014-03-01

To evaluate the impact of different hilar clamping methods on changes in renal function after partial nephrectomy. We analyzed the clinical data of 369 patients who underwent partial nephrectomy for a single renal tumor of size ≤4.0 cm and a normal contralateral kidney. Patients were separated into three groups depending on hilar clamping method: non-clamping, cold ischemia and warm ischemia. Estimated glomerular filtration rate was examined at preoperative, nadir and 1 year postoperatively. Percent change in estimated glomerular filtration rate was used as the parameter to assess the renal functional outcome. Percent change in nadir estimated glomerular filtration rate in the non-clamping group was significantly less compared with the cold ischemia and warm ischemia groups (P < 0.001). However, no significant differences among the groups were noted in percent change of estimated glomerular filtration rate at 1 year (P = 0.348). The cold ischemia group had a similar serial change of postoperative renal function compared with the warm ischemia group. Percent change in 1-year estimated glomerular filtration rate increased with increasing ischemia time in the cold ischemia (P for trend = 0.073) and warm ischemia groups (P for trend = 0.010). On multivariate analysis, hilar clamping (both warm ischemia and cold ischemia) were significantly associated with percent change in nadir estimated glomerular filtration rate, but not in 1-year estimated glomerular filtration rate. Non-clamping partial nephrectomy results in a lower percent change in nadir estimated glomerular filtration rate, whereas it carries an estimated glomerular filtration rate change at 1 year that is similar to partial nephrectomy with cold ischemia and warm ischemia. Cold ischemia and warm ischemia provide a similar effect on renal function. Therefore, when hilar clamping is required, minimization of ischemia time is necessary. © 2013 The Japanese Urological Association.

Adaptive functional change of the contralateral kidney after partial nephrectomy.

PubMed

Choi, Se Young; Yoo, Sangjun; You, Dalsan; Jeong, In Gab; Song, Cheryn; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2017-08-01

Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1 : <30 ml·min -1 ·1.73 m -2 , group 2 : 30-45 ml·min -1 ·1.73 m -2 , and group 3 : ≥45 ml·min -1 ·1.73 m -2 ). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1 , 2 , and 3 , respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [β: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (β: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function. Copyright © 2017 the American Physiological Society.

30-day hospital readmission after robotic partial nephrectomy--are we prepared for Medicare readmission reduction program?

PubMed

Brandao, Luis Felipe; Zargar, Homayoun; Laydner, Humberto; Akca, Oktay; Autorino, Riccardo; Ko, Oliver; Samarasekera, Dinesh; Li, Jianbo; Rabets, John; Krishnan, Jayram; Haber, Georges-Pascal; Kaouk, Jihad; Stein, Robert J

2014-09-01

After CMS introduced the concept of the Hospital Readmissions Reduction Program, hospitals and health care centers became financially penalized for exceeding specific readmission rates. We retrospectively reviewed our institutional review board approved database of patients undergoing robotic partial nephrectomy at our institution and included in our analysis patients who were readmitted to any hospital as an inpatient stay within 30 days from discharge home after robotic partial nephrectomy. From March 2006 to March 2013 a total of 627 patients underwent robotic partial nephrectomy at our center and 28 (4.46%) were readmitted within 30 days of surgery. Postoperative bleeding was responsible for 8 (28.5%) readmissions. Pulmonary embolism was reported in 3 cases and retroperitoneal abscess was diagnosed in 2. Urinary leak requiring surgical intervention developed in 2 patients, pneumonia was diagnosed in 2 and 2 patients were readmitted for chest pain. Overall 9 (32.1%) patients presented with major complications requiring intervention. On multivariable analysis Charlson comorbidity index score was the only factor significantly associated with a higher 30-day readmission rate (p = 0.03). If the Charlson score was 5 or greater the chance of hospital readmission would be 2.7 times higher. Increased comorbidity, specifically a Charlson score of 5 or greater, was the only significant predictor of a higher incidence of 30-day readmission. This information can be useful in counseling patients regarding robotic partial nephrectomy and in determining baseline rates if CMS expands the number of conditions they evaluate for excess 30-day readmissions. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Application of modified R.E.N.A.L. nephrometry score system in evaluating the retroperitoneal partial nephrectomy for T1 renal cell carcinoma.

PubMed

Wang, Qinzhang; Qian, Biao; Li, Qiang; Ni, Zhao; Li, Yinglong; Wang, Xinmin

2015-01-01

This study aims to investigate the application of the modified R.E.N.A.L. nephrometry score system in evaluating the operation difficulty of retroperitoneal partial nephrectomy in T1 renal cell carcinoma patients. A total of 52 patients with T1 renal cell carcinoma were enrolled. They all had retroperitoneal partial nephrectomy. Their clinical data was retrospectively analyzed. R.E.N.A.L. nephrometry score system was modified based on the features of retroperitoneal partial nephrectomy. The specificity, sensitivity and Youden index were compared between R.E.N.A.L. nephrometry score system and the modified R.E.N.A.L. nephrometry score system. The effect of the modified R.E.N.A.L. nephrometry score system on perioperative outcomes was analyzed. Three degrees of operation difficulty were defined by the modified R.E.N.A.L. nephrometry score system, which included the low, medium and high degree of operation difficulty. The specificity, sensitivity and Youden index of the modified R.E.N.A.L. nephrometry score system were better than those of the original R.E.N.A.L. nephrometry score system. Compared with low degree of operation difficulty, patients with medium and high degree of operation difficulty had significantly higher levels of operative time, warm ischemia time, and intraoperative blood loss (P < 0.05). And, the levels of operative time, warm ischemia time, and intraoperative blood loss in patients with high degree were significantly higher than those in patients with medium degree (P < 0.05). The modified R.E.N.A.L. nephrometry score system has a good effect in evaluating the operation difficulty of retroperitoneal partial nephrectomy.

Osteopontin plays a pivotal role in increasing severity of respiratory syncytial virus infection

PubMed Central

Sampayo-Escobar, Viviana; Green, Ryan; Cheung, Michael B.; Bedi, Raminder; Mohapatra, Subhra

2018-01-01

The molecular mechanisms underlying susceptibility to severe respiratory syncytial virus (RSV) infection remain poorly understood. Herein, we report on the role of osteopontin (OPN) in regulation of RSV infection in human epithelial cells and how interleukin-1 beta (IL-1β), a cytokine secreted soon after RSV infection, when persistently expressed can induce OPN expression leading to increased viral infection. We first compared OPN expression in two human epithelial cell lines: HEK-293 and HEp-2. In contrast to HEp-2, HEK-293 expresses low levels of pro-caspase-1 resulting in decreased IL-1β expression in response to RSV infection. We found a correlation between low IL-1β levels and a delay in induction of OPN expression in RSV-infected HEK-293 cells compared to HEp-2. This phenomenon could partially explain the high susceptibility of HEp-2 cells to RSV infection versus the moderate susceptibility of HEK-293 cells. Also, HEK-293 cells expressing low levels of pro-caspase-1 exhibit decreased IL-1β expression and delayed OPN expression in response to RSV infection. HEK-293 cells incubated with human rIL-1β showed a dose-dependent increase in OPN expression upon RSV infection. Also, incubation with rOPN increased RSV viral load. Moreover, HEp-2 cells or mice infected with a mucogenic RSV strain RSV-L19F showed elevated levels of OPN in contrast to mice infected with the laboratory RSV strain rA2. This correlated with elevated levels of OPN following infection with RSV-L19F compared to rA2. Together, these results demonstrate that increased OPN expression is regulated in part by IL-1β, and the interplay between IL-1β and OPN signaling may play a pivotal role in the spread of RSV infection. PMID:29677209

Robotic partial nephrectomy for duplex kidney with ectopic ureter draining in the vagina in an adult patient with urinary incontinence.

PubMed

Mahmood, Humza; Hadjipavlou, Marios; Das, Raj; Anderson, Chris

2017-02-06

A duplex kidney system with an ectopic ureter draining into the vagina is a congenital malformation that typically presents as refractory urinary incontinence. Diagnosis is often difficult to establish and delayed due to a low incidence. We present the case of a patient aged 26 years with a life-long history of persistent urinary incontinence. Initial presentation was at childhood; however, the diagnosis went undetermined for 22 years. CT urography revealed a duplex kidney with an atrophic upper pole associated with an ectopic ureter that drained into the vaginal vault. This is the first description of such a case being managed successfully via a robot-assisted partial nephrectomy approach. Ectopic ureteral duplication should be considered in the differential diagnosis for young women with refractory urinary incontinence. Robotic partial nephrectomy is a safe and effective technique to manage such cases. 2017 BMJ Publishing Group Ltd.

Safety and efficacy of transarterial nephrectomy as an alternative to surgical nephrectomy.

PubMed

Choe, Jooae; Shin, Ji Hoon; Yoon, Hyun-Ki; Ko, Gi-Young; Gwon, Dong Il; Ko, Heung Kyu; Kim, Jin Hyoung; Sung, Kyu-Bo

2014-01-01

To evaluate the safety and efficacy of transarterial nephrectomy, i.e., complete renal artery embolization, as an alternative to surgical nephrectomy. This retrospective study included 11 patients who underwent transarterial nephrectomy due to a high risk of surgical nephrectomy or their refusal to undergo surgery during the period from April 2002 to February 2013. Medical records and radiographic images were reviewed retrospectively to collect information regarding underlying etiologies, clinical presentations and embolization outcomes. The underlying etiologies for transarterial nephrectomy included recurrent hematuria (chronic transplant rejection [n = 3], arteriovenous malformation or fistula [n = 3], angiomyolipoma [n = 1], or end-stage renal disease [n = 1]), inoperable renal or ureteral injury (n = 2), and ectopic kidney with urinary incontinence (n = 1). The technical success rate was 100%, while clinical success was achieved in eight patients (72.7%). Subsequent surgical nephrectomy was required for three patients due to an incomplete nephrectomy effect (n = 2) or necrotic pyelonephritis (n = 1). Procedure-related complications were post-infarction syndrome in one patient and necrotic pyelonephritis in another patient. Of four patients with follow-up CT, four showed renal atrophy and two showed partial renal enhancement. No patient developed a procedure-related hypertension. Transarterial nephrectomy may be a safe and effective alternative to surgical nephrectomy in patients with high operative risks.

Reducing Operating Room Costs Through Real-Time Cost Information Feedback: A Pilot Study.

PubMed

Tabib, Christian H; Bahler, Clinton D; Hardacker, Thomas J; Ball, Kevin M; Sundaram, Chandru P

2015-08-01

To create a protocol for providing real-time operating room (OR) cost feedback to surgeons. We hypothesize that this protocol will reduce costs in a responsible way without sacrificing quality of care. All OR costs were obtained and recorded for robot-assisted partial nephrectomy and laparoscopic donor nephrectomy. Before the beginning of this project, costs pertaining to the 20 most recent cases were analyzed. Items were identified from previous cases as modifiable for replacement or omission. Timely feedback of total OR costs and cost of each item used was provided to the surgeon after each case, and costs were analyzed. A cost analysis of the robot-assisted partial nephrectomy before the washout period indicates expenditures of $5243.04 per case. Ten recommended modifiable items were found to have an average per case cost of $1229.33 representing 23.4% of the total cost. A postwashout period cost analysis found the total OR cost decreased by $899.67 (17.2%) because of changes directly related to the modifiable items. Therefore, 73.2% of the possible identified savings was realized. The same stepwise approach was applied to laparoscopic donor nephrectomies. The average total cost per case before the washout period was $3530.05 with $457.54 attributed to modifiable items. After the washout period, modifiable items costs were reduced by $289.73 (8.0%). No complications occurred in the donor nephrectomy cases while one postoperative complication occurred in the partial nephrectomy group. Providing surgeons with feedback related to OR costs may lead to a change in surgeon behavior and decreased overall costs. Further studies are needed to show equivalence in patient outcomes.

Laparoscopic Partial Nephrectomy With Potassium-titanyl-phosphate Laser Versus Conventional Laparoscopic Partial Nephrectomy: An Animal Randomized Controlled Trial.

PubMed

Rioja, Jorge; Morcillo, Esther; Novalbos, José P; Sánchez-Hurtado, Miguel A; Soria, Federico; Pérez-Duarte, Francisco; Díaz-Güemes Martín-Portugüés, Idoia; Laguna, Maria Pilar; Sánchez-Margallo, Francisco Miguel; Rodríguez-Rubio Cortadellas, Federico

2017-01-01

To explore the feasibility, safety, and short-term results of potassium-titanyl-phosphate (KTP) laser laparoscopic partial nephrectomy (KTP-LPN) vs conventional laparoscopic partial nephrectomy (C-LPN). Thirty large white female pigs were randomized to KTP-LPN or C-LPN. Laparoscopic radical right nephrectomy was performed, and an artificial renal tumor was placed in the left kidney in 3 locations. A week later, 15 pigs underwent C-LPN and 15 underwent KTP-LPN. All C-LPNs were performed with renal ischemia. A 120-W setting was used, without arterial clamping in the KTP-LPN group. Follow-up was done at day 1, week 3, and week 6. Retrograde pyelography was performed at 6 weeks, followed by animal sacrifice and necropsy. All KTP-LPNs were performed without hilar clamping. C-LPNs were performed with hilar clamping, closing of the collecting system, and renorraphy. In the KTP laser group, 2 pigs died due to urinary fistula in the first week after surgery. In the C-LPN group, 1 pig died due to myocardial infarction and another due to malignant hyperthermia. Hemoglobin and hematocrit recovery were lower at 6 weeks in the KTP-LPN group. Renal function 24 hours after surgery was worse in the KTP-LPN group but recovered at 3 weeks and 6 weeks. No differences were observed in surgical margins. The necropsy showed no differences. Limitations of the study are the impossibility to analyze the collecting tissue sealing by the KTP, and the potential renal toxicity of the KTP laser. Although KTP-LPN is feasible and safe in the animal model, further studies are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

A Mathematical Method to Calculate Tumor Contact Surface Area: An Effective Parameter to Predict Renal Function after Partial Nephrectomy.

PubMed

Hsieh, Po-Fan; Wang, Yu-De; Huang, Chi-Ping; Wu, Hsi-Chin; Yang, Che-Rei; Chen, Guang-Heng; Chang, Chao-Hsiang

2016-07-01

We proposed a mathematical formula to calculate contact surface area between a tumor and renal parenchyma. We examined the applicability of using contact surface area to predict renal function after partial nephrectomy. We performed this retrospective study in patients who underwent partial nephrectomy between January 2012 and December 2014. Based on abdominopelvic computerized tomography or magnetic resonance imaging, we calculated the contact surface area using the formula (2*π*radius*depth) developed by integral calculus. We then evaluated the correlation between contact surface area and perioperative parameters, and compared contact surface area and R.E.N.A.L. (Radius/Exophytic/endophytic/Nearness to collecting system/Anterior/Location) score in predicting a reduction in renal function. Overall 35, 26 and 45 patients underwent partial nephrectomy with open, laparoscopic and robotic approaches, respectively. Mean ± SD contact surface area was 30.7±26.1 cm(2) and median (IQR) R.E.N.A.L. score was 7 (2.25). Spearman correlation analysis showed that contact surface area was significantly associated with estimated blood loss (p=0.04), operative time (p=0.04) and percent change in estimated glomerular filtration rate (p <0.001). On multivariate analysis contact surface area and R.E.N.A.L. score independently affected percent change in estimated glomerular filtration rate (p <0.001 and p=0.03, respectively). On ROC curve analysis contact surface area was a better independent predictor of a greater than 10% change in estimated glomerular filtration rate compared to R.E.N.A.L. score (AUC 0.86 vs 0.69). Using this simple mathematical method, contact surface area was associated with surgical outcomes. Compared to R.E.N.A.L. score, contact surface area was a better predictor of functional change after partial nephrectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Development and Validation of a Novel Robotic Procedure Specific Simulation Platform: Partial Nephrectomy.

PubMed

Hung, Andrew J; Shah, Swar H; Dalag, Leonard; Shin, Daniel; Gill, Inderbir S

2015-08-01

We developed a novel procedure specific simulation platform for robotic partial nephrectomy. In this study we prospectively evaluate its face, content, construct and concurrent validity. This hybrid platform features augmented reality and virtual reality. Augmented reality involves 3-dimensional robotic partial nephrectomy surgical videos overlaid with virtual instruments to teach surgical anatomy, technical skills and operative steps. Advanced technical skills are assessed with an embedded full virtual reality renorrhaphy task. Participants were classified as novice (no surgical training, 15), intermediate (less than 100 robotic cases, 13) or expert (100 or more robotic cases, 14) and prospectively assessed. Cohort performance was compared with the Kruskal-Wallis test (construct validity). Post-study questionnaire was used to assess the realism of simulation (face validity) and usefulness for training (content validity). Concurrent validity evaluated correlation between virtual reality renorrhaphy task and a live porcine robotic partial nephrectomy performance (Spearman's analysis). Experts rated the augmented reality content as realistic (median 8/10) and helpful for resident/fellow training (8.0-8.2/10). Experts rated the platform highly for teaching anatomy (9/10) and operative steps (8.5/10) but moderately for technical skills (7.5/10). Experts and intermediates outperformed novices (construct validity) in efficiency (p=0.0002) and accuracy (p=0.002). For virtual reality renorrhaphy, experts outperformed intermediates on GEARS metrics (p=0.002). Virtual reality renorrhaphy and in vivo porcine robotic partial nephrectomy performance correlated significantly (r=0.8, p <0.0001) (concurrent validity). This augmented reality simulation platform displayed face, content and construct validity. Performance in the procedure specific virtual reality task correlated highly with a porcine model (concurrent validity). Future efforts will integrate procedure specific virtual reality tasks and their global assessment. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of clamping technique in robotic partial nephrectomy: does unclamped partial nephrectomy improve perioperative outcomes and renal function?

PubMed

Krane, L Spencer; Mufarrij, Patrick W; Manny, Theodore B; Hemal, Ashok K

2013-02-01

Partial nephrectomy without renal vascular occlusion has been introduced to improve outcomes in patients undergoing robotic partial nephrectomy (RPN). We prospectively evaluated unclamped RPN at our institution and compared this to other clamping techniques in a non-randomized fashion. Ninety-five consecutive patients who successfully completed RPN between June 2010 and October 2011 are included in this analysis. All RPNs were performed by a single surgeon. Clamping technique was artery and vein (AV), artery alone (AO) or unclamped (U) without hypotensive anesthesia. Clamping decision was based on surgeon preference and feasibility of minimizing ischemia. All patients had bilateral functional renal units. Eighteen (19%), 58 (61%) and 19 (20%) patients had AV, AO and U technique respectively. Preoperative characteristics including age (p = 0.43), body mass index (p = 0.40) and RENAL nephromety distribution (p = 0.10) were similar. In AV and AO, mean warm ischemia time were 19 and 17 minutes and similar between the two cohorts (p = 0.39). Mean glomerular filtration rate (GFR) and overall percentage decrease in GFR at time of at last follow up were (64, 69, 81, p = 0.12) and (6%, 6%,and 2%,p = 0.79) for AV, AO and U respectively. Median follow up for last serum creatinine was 113 days and was similar between all cohorts (p = 0.37). Complication rate (p = 0.37), positive margin rate (p = 0.84), and change in hemoglobin concentration postoperatively (p = 0.94) were similar between cohorts. Unclamped partial nephrectomy is possible in patients undergoing RPN. In this study, it does not significantly alter perioperative or postoperative renal function or change rate of complications. Minimal ischemia, irrespective of clamping technique, in patients with bilateral renal units does not appear to adversely effect intermediate term renal function in these patients.

Zero ischemia anatomical partial nephrectomy: a novel approach.

PubMed

Gill, Inderbir S; Patil, Mukul B; Abreu, Andre Luis de Castro; Ng, Casey; Cai, Jie; Berger, Andre; Eisenberg, Manuel S; Nakamoto, Masahiko; Ukimura, Osamu; Goh, Alvin C; Thangathurai, Duraiyah; Aron, Monish; Desai, Mihir M

2012-03-01

We present a novel concept of zero ischemia anatomical robotic and laparoscopic partial nephrectomy. Our technique primarily involves anatomical vascular microdissection and preemptive control of tumor specific, tertiary or higher order renal arterial branch(es) using neurosurgical aneurysm micro-bulldog clamps. In 58 consecutive patients the majority (70%) had anatomically complex tumors including central (67%), hilar (26%), completely intrarenal (23%), pT1b (18%) and solitary kidney (7%). Data were prospectively collected and analyzed from an institutional review board approved database. Of 58 cases undergoing zero ischemia robotic (15) or laparoscopic (43) partial nephrectomy, 57 (98%) were completed without hilar clamping. Mean tumor size was 3.2 cm, mean ± SD R.E.N.A.L. score 7.0 ± 1.9, C-index 2.9 ± 2.4, operative time 4.4 hours, blood loss 206 cc and hospital stay 3.9 days. There were no intraoperative complications. Postoperative complications (22.8%) were low grade (Clavien grade 1 to 2) in 19.3% and high grade (Clavien grade 3 to 5) in 3.5%. All patients had negative cancer surgical margins (100%). Mean absolute and percent change in preoperative vs 4-month postoperative serum creatinine (0.2 mg/dl, 18%), estimated glomerular filtration rate (-11.4 ml/minute/1.73 m(2), 13%), and ipsilateral kidney function on radionuclide scanning at 6 months (-10%) correlated with mean percent kidney excised intraoperatively (18%). Although 21% of patients received a perioperative blood transfusion, no patient had acute or delayed renal hemorrhage, or lost a kidney. The concept of zero ischemia robotic and laparoscopic partial nephrectomy is presented. This anatomical vascular microdissection of the artery first and then tumor allows even complex tumors to be excised without hilar clamping. Global surgical renal ischemia is unnecessary for the majority of patients undergoing robotic and laparoscopic partial nephrectomy at our institution. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A Case Report of Partial Nephrectomy of Mucinous Cystadenocarcinoma in Kidney and Its Literature Review

PubMed Central

Kim, Sung Han; Yuk, Heong Dong; Park, Weon Seo; Kim, Sun Ho; Joung, Jae Young; Seo, Ho Kyung; Lee, Kang Hyun; Chung, Jinsoo

2016-01-01

Mucinous cystadenocarcinoma (MC) of the kidney is a rare epithelial tumor originating from the renal pelvic urothelium and few study cases have been reported. Because of the rarity of these tumors and their unknown histogenesis, its diagnosis is difficult until surgical exploration. We report here on a 55-year-old man referred to the urology department from the hepatology department because of a cystic renal mass measuring approximately 5 cm in size, which was detected incidentally under ultrasonography during the routine examination of liver. The renal mass was finally diagnosed as MC originating from kidney after partial nephrectomy and the patient still showed no evidence of recurrence until 12 months postoperatively. This is the first report on a case of renal MC in a patient who underwent partial nephrectomy. The aim of this report is to present our unusual case of MC and also review the previous literature on the pathological and radiological aspects of MC of kidney. PMID:25687861

Hospitalization for partial nephrectomy was not associated with intrathecal opioid analgesia: Retrospective analysis.

PubMed

Weingarten, Toby N; Del Mundo, Serena B; Yeoh, Tze Yeng; Scavonetto, Federica; Leibovich, Bradley C; Sprung, Juraj

2014-10-01

The aim of this retrospective study is to test the hypothesis that the use of spinal analgesia shortens the length of hospital stay after partial nephrectomy. We reviewed all patients undergoing partial nephrectomy for malignancy through flank incision between January 1, 2008, and June 30, 2011. We excluded patients who underwent tumor thrombectomy, used sustained-release opioids, or had general anesthesia supplemented by epidural analgesia. Patients were grouped into "spinal" (intrathecal opioid injection for postoperative analgesia) versus "general anesthetic" group, and "early" discharge group (within 3 postoperative days) versus "late" group. Association between demographics, patient physical status, anesthetic techniques, and surgical complexity and hospital stay were analyzed using multivariable logistic regression analysis. Of 380 patients, 158 (41.6%) were discharged "early" and 151 (39.7%) were "spinal" cases. Both spinal and early discharge groups had better postoperative pain control and used less postoperative systemic opioids. Spinal analgesia was associated with early hospital discharge, odds ratio 1.52, (95% confidence interval 1.00-2.30), P = 0.05, but in adjusted analysis was no longer associated with early discharge, 1.16 (0.73-1.86), P = 0.52. Early discharge was associated with calendar year, with more recent years being associated with early discharge. Spinal analgesia combined with general anesthesia was associated with improved postoperative pain control during the 1(st) postoperative day, but not with shorter hospital stay following partial nephrectomy. Therefore, unaccounted practice changes that occurred during more recent times affected hospital stay.

Laparoscopic partial nephrectomy for renal tumor: Nagoya experience.

PubMed

Yoshikawa, Yoko; Ono, Yoshinari; Hattori, Ryohei; Gotoh, Momokazu; Yoshino, Yasushi; Katsuno, Satoshi; Katoh, Masashi; Ohshima, Shinichi

2004-08-01

To clarify the indication for a vascular clamp during laparoscopic partial nephrectomy, the clinical results of 17 patients who underwent the procedure for small renal tumors were reviewed. Seventeen patients with renal tumors were enrolled in our laparoscopic partial nephrectomy program between October 1999 and November 2003. During laparoscopy, a vascular clamp was used to remove the tumor mass and suture the incised renal parenchyma and urinary collecting system in 8 patients who had less-than-1-cm-thick renal parenchyma between the mass and the renal sinus or calices. In the remaining 9 patients, who had 1-cm-or-more-thick renal parenchyma between the mass and sinus or calices, renal bleeding was controlled using ultrasonic scissors, gauze tampon, argon beam coagulator, and fibrin glue. Sixteen patients were successfully treated with laparoscopy; one required conversion to open surgery because of uncontrollable bleeding. The average operative time was 4.5 hours, and average estimated bleeding volume was 301 mL. In the 8 patients requiring vascular clamping by forceps, the average ischemic time was 25 minutes. In all patients, the tumor mass was completely removed with negative surgical margins, and renal function was preserved. Three patients had prolonged urinary leakage for a mean of 21 days. Laparoscopic partial nephrectomy offers many advantages, including surgery that is both nephron sparing and minimally invasive. A vascular clamp was indicated for patients with less-than-1-cm-thick renal parenchyma between the tumor mass and renal sinus or calices.

Perioperative outcomes of 6042 nephrectomies in 2012: surgeon-reported results in the UK from the British Association of Urological Surgeons (BAUS) nephrectomy database.

PubMed

Henderson, John M; Fowler, Sarah; Joyce, Adrian; Dickinson, Andrew; Keeley, Francis X

2015-01-01

To present the perioperative outcomes from the British Association of Urological Surgeons (BAUS) nephrectomy dataset for 2012, the first year of public reporting of individual surgeon outcomes in the UK. All nephrectomies performed in the year 2012 and recorded in the database were analysed. These were divided into simple nephrectomy (SN), partial nephrectomy (PN), radical nephrectomy (RN), and nephroureterectomy (NU). The estimated capture rate for nephrectomy was 80%. The outcomes measured were 30-day mortality (30-DM), Clavien-Dindo complications grade ≥III, blood transfusion, conversion to open, and length of stay. The overall 30-DM was 0.55% (SN 0.53%; PN 0.10%; RN 0.52%; NU 1.27%). Clavien-Dindo complications grade ≥III were recorded in 3.9% of nephrectomies (SN 4.3%; PN 5.4%; RN 3.1%; NU 4.5%). Blood transfusion was required during surgical admission for 8.4% of nephrectomies (SN 5.2%; PN 3.4%; RN 11.1%; NU 8.3%). Conversion to open was carried out in 5.5% of minimally invasive nephrectomies (SN 6.1%; PN 4.0%; RN 5.5%; NU 5.6%). Open nephrectomy patients remained in hospital for a median of 6 days (SN 7; PN 5; RN 7; NU 8 days), which was higher than the median 4-day stay (SN 3; PN 4; RN 4; NU 5 days) for minimally invasive surgery. Nephrectomy in 2012 was a safe procedure with morbidity and mortality rates comparable with or less than published series. The collection of surgeon-specific data should be iterative with further refinement of data categories, support for the collection process and independent validation of results. © 2014 The Authors. BJU International © 2014 BJU International.

Provider-based research networks and diffusion of surgical technologies among patients with early-stage kidney cancer.

PubMed

Tan, Hung-Jui; Meyer, Anne-Marie; Kuo, Tzy-Mey; Smith, Angela B; Wheeler, Stephanie B; Carpenter, William R; Nielsen, Matthew E

2015-03-15

Provider-based research networks such as the National Cancer Institute's Community Clinical Oncology Program (CCOP) have been shown to facilitate the translation of evidence-based cancer care into clinical practice. This study compared the utilization of laparoscopy and partial nephrectomy among patients with early-stage kidney cancer according to their exposure to CCOP-affiliated providers. With linked Surveillance, Epidemiology, and End Results-Medicare data, patients with T1aN0M0 kidney cancer who had been treated with nephrectomy from 2000 to 2007 were identified. For each patient, the receipt of care from a CCOP physician or hospital and treatment with laparoscopy or partial nephrectomy were determined. Adjusted for patient characteristics (eg, age, sex, and marital status) and other organizational features (eg, community hospital and National Cancer Institute-designated cancer center), multivariate logistic regression was used to estimate the association between each surgical innovation and CCOP affiliation. During the study interval, 1578 patients (26.8%) were treated by a provider with a CCOP affiliation. Trends in the utilization of laparoscopy and partial nephrectomy remained similar between affiliated and nonaffiliated providers (P ≥ .05). With adjustments for patient characteristics, organizational features, and clustering, no association was noted between CCOP affiliation and the use of laparoscopy (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.81-1.53) or partial nephrectomy (OR, 1.04; 95% CI, 0.82-1.32) despite the more frequent receipt of these treatments in academic settings (P < .05). At a population level, patients treated by providers affiliated with CCOP were no more likely to receive at least 1 of 2 surgical innovations for treatment of their kidney cancer, indicating perhaps a more limited scope to provider-based research networks as they pertain to translational efforts in cancer care. © 2014 American Cancer Society.

Renal function following xenon anesthesia for partial nephrectomy-An explorative analysis of a randomized controlled study.

PubMed

Stevanovic, Ana; Schaefer, Patrick; Coburn, Mark; Rossaint, Rolf; Stoppe, Christian; Boor, Peter; Pfister, David; Heidenreich, Axel; Christ, Hildegard; Hellmich, Martin; Fahlenkamp, Astrid V

2017-01-01

Perioperative preservation of renal function has a significant impact on morbidity and mortality in kidney surgery. Nephroprotective effects of the anesthetic xenon on ischemia-reperfusion injury were found in several experimental studies. We aimed to explore whether xenon anesthesia can reduce renal damage in humans undergoing partial nephrectomy and to gather pilot data of possible nephroprotection in these patients. A prospective randomized, single-blinded, controlled study. Single-center, University Hospital of Aachen, Germany between July 2013-October 2015. Forty-six patients with regular renal function undergoing partial nephrectomy. Patients were randomly assigned to receive xenon- (n = 23) or isoflurane (n = 23) anesthesia. Primary outcome was the maximum postoperative glomerular filtration rate (GFR) decline within seven days after surgery. Secondary outcomes included intraoperative and tumor-related data, assessment of further kidney injury markers, adverse events and optional determination of renal function after 3-6 months. Unexpected radical nephrectomy was performed in 5 patients, thus they were excluded from the per-protocol analysis, but included in the intention-to-treat analysis. The maximum postoperative GFR decline was attenuated by 45% in the xenon-group (10.9 ml min-1 1.73 cm-2 versus 19.7 ml min-1 1.73 cm-2 in the isoflurane group), but without significance (P = 0.084). Occurrence of adverse events was reduced (P = 0.003) in the xenon group. Renal function was similar among the groups after 3-6 months. Xenon anesthesia was feasible and safe in patients undergoing partial nephrectomy with regard to postoperative renal function. We found no significant effect on early renal function but less adverse events in the xenon group. Larger randomized controlled studies in more heterogeneous collectives are required, to confirm or refute the possible clinical benefit on renal function by xenon. ClinicalTrials.gov NCT01839084 and EudraCT 2012-005698-30.

Hospitalization for partial nephrectomy was not associated with intrathecal opioid analgesia: Retrospective analysis

PubMed Central

Weingarten, Toby N.; Del Mundo, Serena B.; Yeoh, Tze Yeng; Scavonetto, Federica; Leibovich, Bradley C.; Sprung, Juraj

2014-01-01

Background: The aim of this retrospective study is to test the hypothesis that the use of spinal analgesia shortens the length of hospital stay after partial nephrectomy. Materials and Methods: We reviewed all patients undergoing partial nephrectomy for malignancy through flank incision between January 1, 2008, and June 30, 2011. We excluded patients who underwent tumor thrombectomy, used sustained-release opioids, or had general anesthesia supplemented by epidural analgesia. Patients were grouped into “spinal” (intrathecal opioid injection for postoperative analgesia) versus “general anesthetic” group, and “early” discharge group (within 3 postoperative days) versus “late” group. Association between demographics, patient physical status, anesthetic techniques, and surgical complexity and hospital stay were analyzed using multivariable logistic regression analysis. Results: Of 380 patients, 158 (41.6%) were discharged “early” and 151 (39.7%) were “spinal” cases. Both spinal and early discharge groups had better postoperative pain control and used less postoperative systemic opioids. Spinal analgesia was associated with early hospital discharge, odds ratio 1.52, (95% confidence interval 1.00-2.30), P = 0.05, but in adjusted analysis was no longer associated with early discharge, 1.16 (0.73-1.86), P = 0.52. Early discharge was associated with calendar year, with more recent years being associated with early discharge. Conclusion: Spinal analgesia combined with general anesthesia was associated with improved postoperative pain control during the 1st postoperative day, but not with shorter hospital stay following partial nephrectomy. Therefore, unaccounted practice changes that occurred during more recent times affected hospital stay. PMID:25422611

The Effect of Patient and Surgical Characteristics on Renal Function After Partial Nephrectomy.

PubMed

Winer, Andrew G; Zabor, Emily C; Vacchio, Michael J; Hakimi, A Ari; Russo, Paul; Coleman, Jonathan A; Jaimes, Edgar A

2018-06-01

The purpose of the study was to identify patient and disease characteristics that have an adverse effect on renal function after partial nephrectomy. We conducted a retrospective review of 387 patients who underwent partial nephrectomy for renal tumors between 2006 and 2014. A line plot with a locally weighted scatterplot smoothing was generated to visually assess renal function over time. Univariable and multivariable longitudinal regression analyses incorporated a random intercept and slope to evaluate the association between patient and disease characteristics with renal function after surgery. Median age was 60 years and most patients were male (255 patients [65.9%]) and white (343 patients [88.6%]). In univariable analysis, advanced age at surgery, larger tumor size, male sex, longer ischemia time, history of smoking, and hypertension were significantly associated with lower preoperative estimated glomerular filtration rate (eGFR). In multivariable analysis, independent predictors of reduced renal function after surgery included advanced age, lower preoperative eGFR, and longer ischemia time. Length of time from surgery was strongly associated with improvement in renal function among all patients. Independent predictors of postoperative decline in renal function include advanced age, lower preoperative eGFR, and longer ischemia time. A substantial number of subjects had recovery in renal function over time after surgery, which continued past the 12-month mark. These findings suggest that patients who undergo partial nephrectomy can experience long-term improvement in renal function. This improvement is most pronounced among younger patients with higher preoperative eGFR. Copyright © 2017 Elsevier Inc. All rights reserved.

Robot-Assisted Partial Nephrectomy for T1b Tumors: Strict Trifecta Outcomes.

PubMed

Tufek, Ilter; Mourmouris, Panagiotis; Doganca, Tunkut; Obek, Can; Argun, Omer Burak; Tuna, Mustafa Bilal; Keskin, Mehmet Selcuk; Kural, Ali Rıza

2017-01-01

"Trifecta" in partial nephrectomy consists of negative surgical margins, minimal renal function decrease and absence of complications. In the present article, our single-center robot-assisted partial nephrectomy (RAPN) experience in T1b renal masses is reported in terms of strict Trifecta outcomes. This is a retrospective analysis of patients with a tumor diameter between 4 and 7 cm (stage T1b), who underwent RAPN by a single surgeon. Preoperative, intraoperative, and postoperative data were recorded and analyzed to evaluate short-term functional and oncologic outcomes. Patients with absence of grade ≥ 2 Clavien-Dindo complications, warm ischemia time (WIT) ≤25 minutes, ≤15% postoperative estimated glomerular filtration rate (eGFR) decrease and negative surgical margins were reported to achieve strict Trifecta outcomes. P < .05 was indicated statistically significant. A total of 150 patients underwent RAPN, and 50 patients were identified with tumor size between 4 and 7 cm. Mean WIT was 20.8 ± 6.2 minutes and mean estimated blood loss (EBL) was 269 ± 191 mL. Surgical margins were negative in all patients. Eleven patients (22%) had a >15% eGFR decrease after surgery. Nine patients (18%) had WIT longer than 25 minutes. Four patients (8%) had grade ≥2 Clavien-Dindo complications. Twenty-nine (58%) patients had strict Trifecta outcomes. Mean follow-up was 44.2 ± 27.2 months. Tumor recurrence was not observed in any patient. Robot-assisted laparoscopic partial nephrectomy for T1b renal masses can be safely performed in experienced hands. Optimal strict Trifecta outcomes and recurrence rates can be achieved.

National Utilization of Partial Nephrectomy Pre- and Post- AUA Guidelines: Is This as Good as It Gets?

PubMed

Sorokin, Igor; Feustel, Paul J; O'Malley, Rebecca L

2017-10-01

The purpose of the study was to compare utilization and predictors of partial nephrectomy (PN) in the pre- and post-guideline eras. American Board of Urology certification/recertification operative logs were reviewed from 2003 to 2014. Nephrectomy cases were extracted using Current Procedural Terminology codes. The cases were then stratified according to pre-guidelines (2003-October 2009) and post-guidelines (November 2009-2014). Multivariable logistic regression was used to evaluate patient, surgeon, and practice characteristics as predictors of PN. A general linear model with regression analysis was used to evaluate the change in PN over time relative to the incidence of renal cell carcinoma (RCC). We identified 20,402 and 20,729 nephrectomies in the pre- and post-guidelines eras, respectively. In multivariable analysis, the post-guidelines group was more likely to undergo PN (odds ratio, 1.87; P < .001). The pre- as well as post-guidelines groups had a higher likelihood of undergoing PN with an open approach, higher-volume surgeons, and younger patient age (P < .05). Surgeon subspecialty and US region were no longer significant factors after guidelines publication. Number of PN normalized to the incidence of RCC continued to increase over time (0.14%/y; R 2  = 0.77; P < .001). Partial nephrectomy in the post-guidelines era is no longer confined to urological subspecialists or certain densely populated US regions. Although rates of PN continue to increase relative to the recently decreasing overall incidence of RCC, the slope has leveled off somewhat. This is likely related to clinical intricacies of the best treatment modality and technologic advances rather than changes related to guidelines publication. Published by Elsevier Inc.

Robotic partial nephrectomy with selective parenchymal compression (Simon clamp).

PubMed

Castillo, O A; Rodriguez-Carlin, A; Lopez-Fontana, G; Aleman, E

2013-01-01

To present our initial experience using selective renal parenchymal ischemia, without hilar clamping, in robotic-assisted partial nephrectomy. In four patients with T1a renal tumor we performed robotic-assisted partial nephrectomy, using the Simon's clamp (Aesculap). It provides selective parenchymal compression without the need of vascular clamping. All patients had exofitic renal tumors in polar location. Renal parenchymal reconstruction was done as the standard technique. The median age was 49.6 years (42-59), 3 male and 1 female patient. Median operative time was 71,6 minutes (40-120). Mean stimated bleeding was 250 ml (50-400). Average tumor size was 3,25 cm (1,5-5,3). There were no complications and the average hospital stay was 3,5 days (1-7). The pathology was informed as renal cell carcinoma in three patients and one hemorrhagic cyst. The surgical margins were negative. Our preliminary results shows that selective renal parenchymal compression, with the Simon's clamp, provides an alternative to vascular control in selected patients with polar renal tumors. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

Indications for nephrectomy in children: what has changed?

PubMed

Nouira, Faouzi; Sarrai, Nadia; Ghorbel, Soufiane; Sghair, Yacoub Ould Med; Khemakhem, Rachid; Chariag, Awatef; Jlidi, Said; Chaouachi, Beji

2010-04-01

The last decade has witnessed significant refinements in preoperative diagnostic evaluation and an improvement in surgical techniques and postoperative management for paediatric patients. There has been an improvement in our understanding of the natural history of some congenital renal anomalies which has caused some changes in management approach. To review the indications for nephrectomy in children between 1996 and 2008, at the departement of paediatric surgery, children's hospital in Tunis. There were 80 nephrectomies. A retrospective review of the patients' notes was performed. The 13-year period was divided into two halves (1996-2000 and 2001-2008) which were then compared. The total number of nephrectomies per year significantly increased over the period of the study (4, 6 and 8 nephrectomies per year for 1996-2000 and 2001-2008, respectively; P < 0.05), as did the number of nephrectomies for Multicystic dysplastic kidney (MCDK) (zero and 5 for 1996-2000 and 2001-2008, respectively) and wilms'tumour (8.3% and 29,16% for 1996 - 2000 and 2001 - 2008, respectively). Wilms' tumour, vesico-ureteric reflux (VUR) and pelvi-ureteric junction (PUJ) obstruction accounted for more than half of the nephrectomies (80% and 58% for 1996-2000 and 2001-2008, respectively). The proportion of nephrectomies performed for VUR did not change (15% and 12% for 1996-2000 and 2001-2008, respectively) but fewer nephrectomies were performed for pelvi-ureteric junction (PUJ) obstruction in the second half of the study period (44% and 4,16% for 1996-2000 and 2001-2008, respectively ; P < 0.05). The total number of nephrectomies, including partial nephrectomies, has increased significantly. The decrease in nephrectomies for PUJ obstruction could be accounted for by a more aggressive approach in the management and follow up of prenatally diagnosed hydronephrosis. Of note is that there was no significant change in the proportion of nephrectomies performed for VUR. On the contrary, the proportion of nephrectomies increased for neoplastic lesions and MCDK.

Treatment options for renal cell carcinoma in renal allografts: a case series from a single institution.

PubMed

Swords, Darden C; Al-Geizawi, Samer M; Farney, Alan C; Rogers, Jeffrey; Burkart, John M; Assimos, Dean G; Stratta, Robert J

2013-01-01

Renal cell carcinoma (RCC) is more common in renal transplant and dialysis patients than the general population. However, RCC in transplanted kidneys is rare, and treatment has previously consisted of nephrectomy with a return to dialysis. There has been recent interest in nephron-sparing procedures as a treatment option for RCC in allograft kidneys in an effort to retain allograft function. Four patients with RCC in allograft kidneys were treated with nephrectomy, partial nephrectomy, or radiofrequency ablation. All of the patients are without evidence of recurrence of RCC after treatment. We found nephron-sparing procedures to be reasonable initial options in managing incidental RCCs diagnosed in functioning allografts to maintain an improved quality of life and avoid immediate dialysis compared with radical nephrectomy of a functioning allograft. However, in non-functioning renal allografts, radical nephrectomy may allow for a higher chance of cure without the loss of transplant function. Consequently, radical nephrectomy should be utilized whenever the allograft is non-functioning and the patient's surgical risk is not prohibitive. © 2013 John Wiley & Sons A/S.

Multiple Renal Artery Pseudoaneurysms in Patients Undergoing Renal Artery Embolization Following Partial Nephrectomy: Correlation with RENAL Nephrometry Scores

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Nakul; Patel, Anish; Ensor, Joe

PurposeTo describe the incidence of multiple renal artery pseudoaneurysms (PSA) in patients referred for renal artery embolization following partial nephrectomy and to study its relationship to RENAL nephrometry scores.Materials and MethodsThe medical records of 25 patients referred for renal artery embolization after partial nephrectomy were retrospectively reviewed for the following parameters: size and number of tumors, RENAL nephrometry scores, angiographic abnormalities, technical and clinical outcomes, and estimated glomerular filtration rates (eGFRs) after embolization.ResultsTwenty-four patients had primary renal tumors, while 1 patient had a pancreatic tumor invading the kidney. Multiple tumors were resected in 4 patients. Most patients (92 %) were symptomatic,more » presenting with gross hematuria, flank pain, or both. Angiography revealed PSA with (n = 5) or without (n = 20) AV fistulae. Sixteen patients (64 %) had multiple PSA involving multiple renal vessels. Higher RENAL nephrometry scores were associated with an increasing likelihood of multiple PSA. Multiple vessels were embolized in 14 patients (56 %). Clinical success was achieved after one (n = 22) or two (n = 3) embolization sessions in all patients. Post-embolization eGFR values at different time points after embolization were not significantly different from the post-operative eGFR.ConclusionA majority of patients requiring renal artery embolization following partial nephrectomy have multiple pseudoaneurysms, often requiring selective embolization of multiple vessels. Higher RENAL nephrometry score is associated with an increasing likelihood of multiple pseudoaneurysms. We found transarterial embolization to be a safe and effective treatment option with no long-term adverse effect on renal function in all but one patient with a solitary kidney.« less

Application and analysis of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for patients with multiple renal tumor: initial experience.

PubMed

Zhu, Jundong; Jiang, Fan; Li, Pu; Shao, Pengfei; Liang, Chao; Xu, Aiming; Miao, Chenkui; Qin, Chao; Wang, Zengjun; Yin, Changjun

2017-09-11

To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for the patients with multiple renal tumor of who have solitary kidney or contralateral kidney insufficiency. Nine patients who have undergone retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping between October 2010 and January 2017 were retrospectively analyzed. Clinical materials and parameters during and after the operation were summarized. Nineteen tumors were resected in nine patients and the operations were all successful. The operation time ranged from 100 to 180 min (125 min); clamping time of segmental renal artery was 10 ~ 30 min (23 min); the amount of blood loss during the operation was 120 ~ 330 ml (190 ml); hospital stay after the operation is 3 ~ 6d (5d). There was no complication during the perioperative period, and the pathology diagnosis after the surgery showed that there were 13 renal clear cell carcinomas, two papillary carcinoma and four perivascular epithelioid cell tumors with negative margins from the 19 tumors. All patients were followed up for 3 ~ 60 months, and no local recurrence or metastasis was detected. At 3-month post-operation follow-up, the mean serum creatinine was 148.6 ± 28.1 μmol/L (p = 0.107), an increase of 3.0 μmol/L from preoperative baseline. For the patients with multiple renal tumors and solitary kidney or contralateral kidney insufficiency, retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping was feasible and safe, which minimized the warm ischemia injury to the kidney and preserved the renal function effectively.

Effect of Regional Hospital Competition and Hospital Financial Status on the Use of Robotic-Assisted Surgery.

PubMed

Wright, Jason D; Tergas, Ana I; Hou, June Y; Burke, William M; Chen, Ling; Hu, Jim C; Neugut, Alfred I; Ananth, Cande V; Hershman, Dawn L

2016-07-01

Despite the lack of efficacy data, robotic-assisted surgery has diffused rapidly into practice. Marketing to physicians, hospitals, and patients has been widespread, but how this marketing has contributed to the diffusion of the technology remains unknown. To examine the effect of regional hospital competition and hospital financial status on the use of robotic-assisted surgery for 5 commonly performed procedures. A cohort study of 221 637 patients who underwent radical prostatectomy, total nephrectomy, partial nephrectomy, hysterectomy, or oophorectomy at 1370 hospitals in the United States from January 1, 2010, to December 31, 2011, was conducted. The association between hospital competition, hospital financial status, and performance of robotic-assisted surgery was examined. The association between hospital competition was measured with the Herfindahl-Hirschman Index (HHI), hospital financial status was estimated as operating margin, and performance of robotic-assisted surgery was examined using multivariate mixed-effects regression models. We identified 221 637 patients who underwent one of the procedures of interest. The cohort included 30 345 patients who underwent radical prostatectomy; 20 802, total nephrectomy; 8060, partial nephrectomy; 134 985, hysterectomy; and 27 445, oophorectomy. Robotic-assisted operations were performed for 20 500 (67.6%) radical prostatectomies, 1405 (6.8%) total nephrectomies, 2759 (34.2%) partial nephrectomies, 14 047 (10.4%) hysterectomies, and 1782 (6.5%) oophorectomies. Use of robotic-assisted surgery increased for each procedure from January 2010 through December 2011. For all 5 operations, increased market competition (as measured by the HHI) was associated with increased use of robotic-assisted surgery. For prostatectomy, the risk ratios (95% CIs) for undergoing a robotic-assisted procedure were 2.20 (1.50-3.24) at hospitals in moderately competitive markets and 2.64 (1.84-3.78) for highly competitive markets compared with noncompetitive markets. For hysterectomy, patients at hospitals in moderately (3.75 [2.26-6.25]) and highly (5.30; [3.27-8.57]) competitive markets were more likely to undergo a robotic-assisted surgery. Increased hospital profitability was associated with use of robotic-assisted surgery only for partial nephrectomy in facilities with medium-high (1.67 [1.13-2.48]) and high (1.50 [0.98-2.29]) operating margins. With analysis limited to patients treated at a hospital that had performed robotic-assisted surgery, there was no longer an association between competition and use of robotic-assisted surgery. Patients undergoing surgery in a hospital in a competitive regional market were more likely to undergo a robotic-assisted procedure. These data imply that regional competition may influence a hospital's decision to acquire a surgical robot.

[Comparison of validity and safety between holmium: YAG laser and traditional surgery in partial nephrectomy].

PubMed

Bi, Sheng; Xia, Ming

2015-08-11

To compare the validity and safety between holmium: YAG laser and traditional surgery in partial nephrectomy. A total of 28 patients were divided into two groups (holmium: YAG laser group without renal artery clamping and traditional surgery group with renal artery clamping). The intraoperative blood loss, total operative time, renal artery clamping time, postoperative hospital stay, separated renal function, postoperative complications and depth of tissue injury were recorded. The intraoperative blood loss, total operative time, renal artery clamping time, postoperative hospital stay, separated renal function, postoperative complications and depth of tissue injury were 80 ml, 77 min, 0 min, 7.4 days, 35 ml/min, 0, 0.9 cm, respectively, in holmium: YAG laser group. And in traditional surgery group were 69 ml, 111 min, 25.5 min, 7.3 days, 34 ml/min, 0, 2.0 cm, respectively. The differences of total operative time, renal artery clamping time and depth of tissue injury between two groups were statistically significant. The others were not statistically significant. Holmium: YAG laser is effective and safe in partial nephrectomy. It can decrease the total operative time, minimize the warm ischemia time and enlarge the extent of surgical excision.

Diode laser supported partial nephrectomy in laparoscopic surgery: preliminary results

NASA Astrophysics Data System (ADS)

Sroka, Ronald; Hennig, Georg; Zillinberg, Katja; Khoder, Wael Y.

2011-07-01

Introduction: Warm ischemia and bleeding during laparoscopic partial nephrectomy place technical constraints on surgeons. Therefore it was the aim to develop a safe and effective laser assisted partial nephrectomy technique without need for ischemia. Patients and methods: A diode laser emitting light at 1318nm in cw mode was coupled into a bare fibre (core diameter 600 μm) thus able to transfer up to 100W to the tissue. After dry lab experience, a total of 8 patients suffering from kidney malformations underwent laparoscopic/retroperitoneoscopic partial nephrectomy. Clinically, postoperative renal function and serum c-reactive protein (CRP) were monitored. Laser induced coagulation depth and effects on resection margins were evaluated. Demographic, clinical and follow-up data are presented. Results: Overall interventions, the mean operative time was 116,5 minutes (range 60-175min) with mean blood loss of 238ml (range 50-600ml) while laser assisted resection of the kidney tissue took max 15min. After extirpation of the tumours all patients showed clinical favourable outcome during follow up period. The tumour size was measured to be 1.8 to 5cm. With respect to clinical safety and due to blood loos, two warm ischemia (19 and 24min) must be performed. Immediate postoperative serum creatinine and CRP were elevated within 0.1 to 0.6 mg/dl (mean 0.18 mg/dl) and 2.1-10 mg/dl (mean 6.24 mg/dl), respectively. The depth of the coagulation on the removed tissue ranged between <1 to 2mm without effect on histopathological evaluation of tumours or resection margin. As the surface of the remaining kidney surface was laser assisted coagulated after removal. The sealing of the surface was induced by a slightly larger coagulation margin, but could not measured so far. Conclusion: This prospective in-vivo feasibility study shows that 1318nm-diode laser assisted partial nephrectomy seems to be a safe and promising medical technique which could be provided either during open surgery as well as laparascopically. This application showed good haemostasis and minimal parenchymal damage. Oncological safety appears to be warranted by the use of diode laser. Further investigations and development are needed for on-line detection of the remain coagulation margin, optimisation of the treatment equipment, and finally to train the application technique.

Current Status of Nephron-Sparing Surgery (NSS) in the Management of Renal Tumours.

PubMed

Venkatramani, Vivek; Swain, Sanjaya; Satyanarayana, Ramgopal; Parekh, Dipen J

2017-06-01

Nephron-sparing surgery has emerged as the surgical treatment of choice for small renal masses over the past two decades, replacing the traditional teaching of radical nephrectomy for renal cell carcinoma. With time, there has been an evolution in the techniques and indications for partial nephrectomy. This review summarizes the current status of nephron-sparing surgery for renal carcinoma and also deals with the future of this procedure.

Wilms Tumor in a Child With Bilateral Polycystic Kidneys and PHACE Syndrome: Successful Treatment Outcome Using Partial Nephrectomy and Chemotherapy.

PubMed

Thankamony, Priyakumari; Sivarajan, Venugopal; Mony, Rari P; Muraleedharan, Venugopal

2016-01-01

Congenital anomalies may be associated with Wilms tumor either as isolated anomalies or as part of a congenital malformation syndrome. Nephroblastoma occurring in association with polycystic kidneys is very rare. The optimal surgical management of nephroblastoma in the setting of polycystic kidneys is not defined because of the rarity of this presentation. PHACE syndrome includes posterior fossa anomalies, hemangioma, arterial lesions, cardiac abnormalities/coarctation of aorta, and eye abnormalities. We report a 17-month-old baby with bilateral polycystic kidneys and PHACE syndrome who developed nephroblastoma in the right polycystic kidney which was treated successfully with nephron-sparing partial nephrectomy and chemotherapy.

Toward a Flexible Variable Stiffness Endoport for Single-Site Partial Nephrectomy.

PubMed

Amanov, E; Nguyen, T-D; Markmann, S; Imkamp, F; Burgner-Kahrs, J

2018-05-31

Laparoscopic partial nephrectomy for localized renal tumors is an upcoming standard minimally invasive surgical procedure. However, a single-site laparoscopic approach would be even more preferable in terms of invasiveness. While the manual approach offers rigid curved tools, robotic single-site systems provide high degrees of freedom manipulators. However, they either provide only a straight deployment port, lack of instrument integration, or cannot be reconfigured. Therefore, the current main shortcomings of single-site surgery approaches include limited tool dexterity, visualization, and intuitive use by the surgeons. For partial nephrectomy in particular, the accessibility of the tumors remains limited and requires invasive kidney mobilization (separation of the kidney from the surrounding tissue), resulting in patient stress and prolonged surgery. We address these limitations by introducing a flexible, robotic, variable stiffness port with several working channels, which consists of a two-segment tendon-driven continuum robot with integrated granular and layer jamming for stabilizing the pose and shape. We investigate biocompatible granules for granular jamming and demonstrate the stiffening capabilities in terms of pose and shape accuracy with experimental evaluations. Additionally, we conduct in vitro experiments on a phantom and prove that the visualization of tumors at various sites is increased up to 38% in comparison to straight endoscopes.

Hand-assisted laparoscopic versus robot-assisted laparoscopic partial nephrectomy: comparison of short-term outcomes and cost.

PubMed

Elsamra, Sammy E; Leone, Andrew R; Lasser, Michael S; Thavaseelan, Simone; Golijanin, Dragan; Haleblian, George E; Pareek, Gyan

2013-02-01

Robot-assisted laparoscopic partial nephrectomy (RALPN) and laparoscopic partial nephrectomy (LPN) have become standard for the surgical management of small renal masses (SRMs). However, no studies have evaluated the short-term outcomes or cost of RALPN as compared with hand-assisted laparoscopic partial nephrectomy (HALPN) in a standardized fashion. A retrospective review of all patients who underwent HALPN or RALPN from 2006 to 2010 were assessed for patient age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, radiographic tumor size, nephrometry (radius, endo/exophytic, nearness to collecting system, anterior/posterior, lines of polarity [RENAL]) scores, operative and room times, hospital length of stay (LOS), estimated blood loss (EBL), requirement of hilar vessel clamping, warm ischemia time (WIT), pre- and postprocedural creatinine and hemoglobin levels, and complications. Total costs of the procedures were estimated based on operating room component (operative staff time, anesthesia, and supply) and hospital stay cost (room and board, pharmacy). A robotic premium cost, estimated based on the yearly overall cost of the da Vinci S surgical system divided by the annual number of cases, was included in the RALPN cost. Cost figures were obtained from hospital administration and applied to the mean HALPN and RALPN patient. Forty-seven patients underwent HALPN since 2006 and 21 patients underwent RALPN since 2008. ASA, BMI, EBL, tumor size, nephrometry score, positive margin rate, change in creatinine, change in hemoglobin, morphine equivalents used, and complication rate were all similar in both groups (p>0.05). Room time and operative time were significantly shorter for the HALPN cohort (p=0.001) whereas LOS was significantly shorter in the RALPN cohort (p=0.019). Despite the shorter LOS, RALPN was associated with a $1165 increased cost, mainly due to increased operating room time and premium cost of the robot. While early in our experience, RALPN offered no significant advantage in short-term outcomes over HALPN and was associated with an increased cost of over $1150.

Potassium-titanyl-phosphate laser assisted robotic partial nephrectomy in a porcine model: can robotic assistance optimize the power needed for effective cutting and hemostasis?

PubMed

Boris, Ronald S; Eun, Daniel; Bhandari, Akshay; Lyall, Kathryn; Bhandari, Mahendra; Rogers, Craig; Alassi, Osama; Menon, Mani

2007-01-01

A potassium-titanyl-phosphate (KTP) laser through robotic endo-wrist instrument has been evaluated as an ablative and hemostatic tool in robotic assisted laparoscopic partial nephrectomy (RALPN). Ten RALPN were performed in five domestic female pigs. The partial nephrectomies were performed with bulldog clamping of the pedicle. Flexible glass fiber carrying 532-nm green light laser was used through a robotic endowrist instrument in two cases. Power usage from 4 to 10 W was tested. The laser probe was explored both as a cutting knife and for hemostasis. The pelvicalyceal system was closed with a running suture. Partial nephrectomies using KTP laser were performed without complications. Mean operative times and warm ischemia times for laser cases were 96 and 18 min, respectively. Mean estimated blood loss was 60 ml compared with 50 ml for non-laser cases. Complete hemostasis with the laser alone could be achieved with a power of 4 W and was found to be effective. In our hands the laser fiber powered up to 10 W was not effective as a quick cutting agent. Histopathologic analysis of the renal remnant revealed a cauterized surface effect with average laser penetration depth less than 1 mm and minimal surrounding cellular injury. The new robotic endowrist instrument carrying flexible glass fiber transmitting 532-nm green light laser is a useful addition to the armamentarium of the robotic urologic setup. Its control by the console surgeon enables quicker and more complete hemostasis of the cut surface in renal sparing surgery using a porcine model. Histologically proven lased depth of less than 1 mm suggests minimal parenchyma damage in an acute setting. Laser application as a cutting agent, however, requires further investigation with interval power settings beyond the limits of this preliminary study. We estimate that effective cutting should be possible with a setting lower than traditionally recommended for solid organs.

Positive surgical margins in robot-assisted partial nephrectomy: a multi-institutional analysis of oncologic outcomes (leave no tumor behind).

PubMed

Khalifeh, Ali; Kaouk, Jihad H; Bhayani, Sam; Rogers, Craig; Stifelman, Michael; Tanagho, Youssef S; Kumar, Ramesh; Gorin, Michael A; Sivarajan, Ganesh; Samarasekera, Dinesh; Allaf, Mohamad E

2013-11-01

Expanding indications for robot-assisted partial nephrectomy raise major oncologic concerns for positive surgical margins. Previous reports showed no correlation between positive surgical margins and oncologic outcomes. We report a multi-institutional experience with the oncologic outcomes of positive surgical margins on robot-assisted partial nephrectomy. Pathological and clinical followup data were reviewed from an institutional review board approved, prospectively maintained joint database from 5 institutions. Tumors with malignant pathology were isolated and statistically analyzed for demographics and oncologic followup. The log rank test was used to compare recurrence-free and metastasis-free survival between patients with positive and negative surgical margins. The proportional hazards method was used to assess the influence of multiple factors, including positive surgical margins, on recurrence and metastasis. A total of 943 robot-assisted partial nephrectomies for malignant tumors were successfully completed. Of the patients 21 (2.2%) had positive surgical margins on final pathological assessment, resulting in 2 groups, including the 21 with positive surgical margins and 922 with negative surgical margins. Positive surgical margin cases had higher recurrence and metastasis rates (p<0.001). As projected by the Kaplan-Meier method in the population as a whole at followup out to 63.6 months, 5-year recurrence-free and metastasis-free survival was 94.8% and 97.5%, respectively. There was a statistically significant difference in recurrence-free and metastasis-free survival between patients with positive and negative surgical margins (log rank test<0.001), which favored negative surgical margins. Positive surgical margins showed an 18.4-fold higher HR for recurrence when adjusted for multiple tumors, tumor size, tumor growth pattern and pathological stage. Positive surgical margins on final pathological evaluation increase the HR of recurrence and metastasis. In addition to pathological and molecular tumor characteristics, this should be considered to plan appropriate management. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The role of the assistant during robot-assisted partial nephrectomy: does experience matter?

PubMed

Potretzke, Aaron M; Knight, Brent A; Brockman, John A; Vetter, Joel; Figenshau, Robert S; Bhayani, Sam B; Benway, Brian M

2016-06-01

The objective of this study was to evaluate surgical outcomes with respect to the experience level of the bedside assistant during robot-assisted partial nephrectomy. A retrospective review was conducted of a prospectively maintained database of 414 consecutive robot-assisted laparoscopic partial nephrectomies performed by experienced robotic surgeons at our institution from April 2011 to September 2014. A senior-level assistant was defined as a resident in his or her post-graduate year (PGY) 4 or 5, or a fellow. Junior-level assistants were considered to be PGY-2, PGY-3, or a nurse first assistant. Multivariate analyses were performed using linear, Poisson, and logistic regression models. There were 115 junior-level cases and 299 senior-level cases. On univariate analysis, the experience level of the assistant had no impact on operative time (168 for junior level vs. 163 min for senior level, p = 0.656). Likewise, there were no differences between the junior- and senior-level groups with regard to warm ischemia time (21.3 vs. 20.9 min, p = 0.843), negative margin status (111/115 (96.5 %) vs. 280/299 (93.6 %), p = 0.340), or postoperative complications (17/115 (14.8 %) vs. 35/299 (11.7 %), p = 0.408). After multivariate analysis, operative time was associated with increased body mass index and tumor size (both p < 0.001), but not with resident experience level (p = 0.051). Estimated blood loss and postoperative complications were also not associated with the PGY of the assistant (p = 0.488 and p = 0.916, respectively). Despite common concern, the PGY status of a physician trainee serving as the bedside assistant does not appear to influence the outcomes of robot-assisted partial nephrectomy at a high-volume center.

Chronic Kidney Disease Epidemiology Collaboration versus Modification of Diet in Renal Disease equations for renal function evaluation in patients undergoing partial nephrectomy.

PubMed

Shikanov, Sergey; Clark, Melanie A; Raman, Jay D; Smith, Benjamin; Kaag, Matthew; Russo, Paul; Wheat, Jeffrey C; Wolf, J Stuart; Huang, William C; Shalhav, Arieh L; Eggener, Scott E

2010-11-01

A novel equation, the Chronic Kidney Disease Epidemiology Collaboration, has been proposed to replace the Modification of Diet in Renal Disease for estimated glomerular filtration rate due to higher accuracy, particularly in the setting of normal renal function. We compared these equations in patients with 2 functioning kidneys undergoing partial nephrectomy. We assembled a cohort of 1,158 patients from 5 institutions who underwent partial nephrectomy between 1991 and 2009. Only subjects with 2 functioning kidneys were included in the study. The end points were baseline estimated glomerular filtration rate, last followup estimated glomerular filtration rate (3 to 18 months), absolute and percent change estimated glomerular filtration rate ([absolute change/baseline] × 100%), and proportion of newly developed chronic kidney disease stage III. The agreement between the equations was evaluated using Bland-Altman plots and the McNemar test for paired observations. Mean baseline estimated glomerular filtration rate derived from the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations were 73 and 77 ml/minute/1.73 m(2), respectively, and following surgery were 63 and 67 ml/minute/1.73 m(2), respectively. Mean percent change estimated glomerular filtration rate was -12% for both equations (p = 0.2). The proportion of patients with newly developed chronic kidney disease stage III following surgery was 32% and 25%, according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations, respectively (p = 0.001). For patients with 2 functioning kidneys undergoing partial nephrectomy the Chronic Kidney Disease Epidemiology Collaboration equation provides slightly higher glomerular filtration rate estimates compared to the Modification of Diet in Renal Disease equation, with 7% fewer patients categorized as having chronic kidney disease stage III or worse. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Comparing renal function preservation after laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for clinical T1a renal tumor: using a 3D parenchyma measurement system.

PubMed

Zhu, Liangsong; Wu, Guangyu; Huang, Jiwei; Wang, Jianfeng; Zhang, Ruiyun; Kong, Wen; Xue, Wei; Huang, Yiran; Chen, Yonghui; Zhang, Jin

2017-05-01

To compare the renal function preservation between laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy. Data were analyzed from 246 patients who underwent laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for solitary cT1a renal cell carcinoma from January 2013 to July 2015. To reduce the intergroup difference, we used a 1:1 propensity matching analysis. The functional renal parenchyma volume preservation were measured preoperative and 12 months after surgery. The total renal function recovery and spilt GFR was compared. Multivariable logistic analysis was used for predictive factors for renal function decline. After 1:1 propensity matching, each group including 100 patients. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation had a smaller decrease in estimate glomerular filtration rate at 1 day (-7.88 vs -20.01%, p < 0.001), 3 months (-2.31 vs -10.39%, p < 0.001), 6 months (-2.16 vs -7.99%, p = 0.015), 12 months (-3.26 vs -8.03%, p = 0.012) and latest test (-3.24 vs -8.02%, p = 0.040), also had better functional renal parenchyma volume preservation (89.19 vs 84.27%, p < 0.001), lower decrease of the spilt glomerular filtration rate (-9.41 vs -17.13%, p < 0.001) at 12 months. The functional renal parenchyma volume preservation, warm ischemia time and baseline renal function were the important independent factors in determining long-term functional recovery. The laparoscopic radio frequency ablation assisted tumor enucleation technology has unique advantage and potential in preserving renal parenchyma without ischemia damage compared to conventional laparoscopic partial nephrectomy, and had a better outcome, thus we recommend this technique in selected T1a patients.

Clinical application of calculated split renal volume using computed tomography-based renal volumetry after partial nephrectomy: Correlation with technetium-99m dimercaptosuccinic acid renal scan data.

PubMed

Lee, Chan Ho; Park, Young Joo; Ku, Ja Yoon; Ha, Hong Koo

2017-06-01

To evaluate the clinical application of computed tomography-based measurement of renal cortical volume and split renal volume as a single tool to assess the anatomy and renal function in patients with renal tumors before and after partial nephrectomy, and to compare the findings with technetium-99m dimercaptosuccinic acid renal scan. The data of 51 patients with a unilateral renal tumor managed by partial nephrectomy were retrospectively analyzed. The renal cortical volume of tumor-bearing and contralateral kidneys was measured using ImageJ software. Split estimated glomerular filtration rate and split renal volume calculated using this renal cortical volume were compared with the split renal function measured with technetium-99m dimercaptosuccinic acid renal scan. A strong correlation between split renal function and split renal volume of the tumor-bearing kidney was observed before and after surgery (r = 0.89, P < 0.001 and r = 0.94, P < 0.001). The preoperative and postoperative split estimated glomerular filtration rate of the operated kidney showed a moderate correlation with split renal function (r = 0.39, P = 0.004 and r = 0.49, P < 0.001). The correlation between reductions in split renal function and split renal volume of the operated kidney (r = 0.87, P < 0.001) was stronger than that between split renal function and percent reduction in split estimated glomerular filtration rate (r = 0.64, P < 0.001). The split renal volume calculated using computed tomography-based renal volumetry had a strong correlation with the split renal function measured using technetium-99m dimercaptosuccinic acid renal scan. Computed tomography-based split renal volume measurement before and after partial nephrectomy can be used as a single modality for anatomical and functional assessment of the tumor-bearing kidney. © 2017 The Japanese Urological Association.

Selective Arterial Clamping Versus Hilar Clamping for Minimally Invasive Partial Nephrectomy.

PubMed

Yezdani, Mona; Yu, Sue-Jean; Lee, David I

2016-05-01

Partial nephrectomy has become an accepted treatment of cT1 renal masses as it provides improved long-term renal function compared to radical nephrectomy (Campbell et al. J Urol. 182:1271-9, 2009). Hilar clamping is utilized to help reduce bleeding and improve visibility during tumor resection. However, concern over risk of kidney injury with hilar clamping has led to new techniques to reduce length of warm ischemia time (WIT) during partial nephrectomy. These techniques have progressed over the years starting with early hilar unclamping, controlled hypotension during tumor resection, selective arterial clamping, minimal margin techniques, and off-clamp procedures. Selective arterial clamping has progressed significantly over the years. The main question is what are the exact short- and long-term renal effects from increasing clamp time. Moreover, does it make sense to perform these more time-consuming or more complex procedures if there is no long-term preservation of kidney function? More recent studies have shown no difference in renal function 6 months from surgery when selective arterial clamping or even hilar clamping is employed, although there is short-term improved decline in estimated glomerular filtration rate (eGFR) with selective clamping and off-clamp techniques (Komninos et al. BJU Int. 115:921-8, 2015; Shah et al. 117:293-9, 2015; Kallingal et al. BJU Int. doi: 10.1111/bju.13192, 2015). This paper reviews the progression of total hilar clamping to selective arterial clamping (SAC) and the possible difference its use makes on long-term renal function. SAC may be attempted based on surgeon's decision-making, but may be best used for more complex, larger, more central or hilar tumors and in patients who have renal insufficiency at baseline or a solitary kidney.

Robotic partial nephrectomy for renal cell carcinomas with venous tumor thrombus.

PubMed

Abaza, Ronney; Angell, Jordan

2013-06-01

To describe the first report of robotic partial nephrectomies (RPNs) for renal cell carcinoma (RCC) with venous tumor thrombus (VTT). Partial nephrectomy for RCC extending into the renal vein has been described in limited fashion, but such a complex procedure has not previously been reported in minimally-invasive fashion. We demonstrate the feasibility of robotic nephron-sparing surgery despite vein thrombi and the results of the initial four highly-selected patients to have undergone this novel procedure. Two patients underwent RPN for RCC with VTT involving intraparenchymal vein branches, and 2 others had VTT involving the main renal vein. Mean patient age was 65 years (range 50-74 years). Mean tumor size was 7.75 cm (range 4.3-12.8 cm) with mean RENAL (radius, exophytic/endophytic, nearness to collecting system, anterior/posterior, and location) nephrometry score of 9.75 (range 8-12). Mean warm ischemia time was 24.2 minutes (range 19-27 minutes) and mean estimated blood loss was 168.8 mL (range 100-300 mL). No patients required transfusion, and there were no intraoperative complications. No patients required conversion to open or standard laparoscopic surgery. All 4 patients were discharged home on the first postoperative day. A single postoperative complication occurred in 1 patient who was readmitted with an ileus that resolved spontaneously. All patients had negative surgical margins. Two patients developed metastatic disease on surveillance imaging. RPN in patients with VTT is safe and feasible in selected patients. Given the risk of metastatic disease in patients with pathologic stage T3a RCC, the role of nephron sparing requires further evaluation such that radical nephrectomy remains the standard of care. Copyright © 2013 Elsevier Inc. All rights reserved.

A rare case of acute presentation of trocar site hernia from robot-assisted laparoscopic partial nephrectomy.

PubMed

Ng, Zi Qin; Pemberton, Richard; Tan, Patrick

2018-02-15

Trocar site hernia is not a common acute complication encountered after robot-assisted surgery, especially in the urological cohort of patients. A few case reports of small bowel obstruction secondary to incarceration by trocar site hernia have been described in gynaecological surgery and prostatectomies. As the clinical presentation is non-specific, late diagnosis has significant implication on morbidity and mortality. Here, we present a rare case of a patient with recent robot-assisted laparoscopic partial nephrectomy for a renal cell carcinoma presented with features of impending bowel obstruction secondary to incarcerated small bowel in the trocar site. We also reviewed the literature focusing on clinical features of trocar site hernia and preventive measures.

Anatomic features involved in technical complexity of partial nephrectomy.

PubMed

Hou, Weibin; Yan, Weigang; Ji, Zhigang

2015-01-01

Nephrometry score systems, including RENAL nephrometry, preoperative aspects and dimensions used for an anatomical classification system, C-index, diameter-axial-polar nephrometry, contact surface area score, calculating resected and ischemized volume, renal tumor invasion index, surgical approach renal ranking score, zonal NePhRO score, and renal pelvic score, have been reviewed. Moreover, salient anatomic features like the perinephric fat and vascular variants also have been discussed. We then extract 7 anatomic characteristics, namely tumor size, spatial location, adjacency, exophytic/endophytic extension, vascular variants, pelvic anatomy, and perinephric fat as important features for partial nephrectomy. For novice surgeons, comprehensive and adequate anatomic consideration may help them in their early clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Stone formation from nonabsorbable clip migration into the collecting system after robot-assisted partial nephrectomy.

PubMed

Lee, Ziho; Reilly, Christopher E; Moore, Blake W; Mydlo, Jack H; Lee, David I; Eun, Daniel D

2014-01-01

We describe a case in which a Weck Hem-o-lok clip (Teleflex, Research Triangle Park, USA) migrated into the collecting system and acted as a nidus for stone formation in a patient after robot-assisted partial nephrectomy. The patient presented 2 years postoperatively with left-sided renal colic. Abdominal computed tomography scan showed a 10 millimeter renal calculus in the left middle pole. After using laser lithotripsy to fragment the overlying renal stone, a Weck Hem-o-lok clip was found to be embedded in the collecting system. A laser fiber through a flexible ureteroscope was used to successfully dislodge the clip from the renal parenchyma, and a stone basket was used to extract the clip.

Reverse right ventricular structural and extracellular matrix remodeling by estrogen in severe pulmonary hypertension

PubMed Central

Nadadur, Rangarajan D.; Umar, Soban; Wong, Gabriel; Eghbali, Mansour; Iorga, Andrea; Matori, Humann; Partow-Navid, Rod

2012-01-01

Chronic pulmonary hypertension (PH) leads to right-ventricular failure (RVF) characterized by RV remodeling. Ventricular remodeling is emerging as an important process during heart failure and recovery. Remodeling in RVF induced by PH is not fully understood. Recently we discovered that estrogen (E2) therapy can rescue severe preexisting PH. Here, we focused on whether E2 (42.5 μg·kg−1·day−1, 10 days) can reverse adverse RV structural and extracellular matrix (ECM) remodeling induced by PH using monocrotaline (MCT, 60 mg/kg). RV fibrosis was evident in RVF males. Intact females developed less severe RV remodeling compared with males and ovariectomized (OVX) females. Novel ECM-degrading disintegrin-metalloproteinases ADAM15 and ADAM17 transcripts were elevated ∼2-fold in all RVF animals. E2 therapy reversed RV remodeling in all groups. In vitro, E2 directly inhibited ANG II-induced expression of fibrosis markers as well as the metalloproteinases in cultured cardiac fibroblasts. Estrogen receptor-β agonist diarylpropionitrile (DPN) but not estrogen receptor-α agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) was as effective as E2 in inhibiting expression of these genes. Expression of ECM-interacting cardiac fetal-gene osteopontin (OPN) also increased ∼9-fold in RVF males. Intact females were partially protected from OPN upregulation (∼2-fold) but OVX females were not. E2 reversed OPN upregulation in all groups. Upregulation of OPN was also reversed in vitro by E2. Plasma OPN was elevated in RVF (∼1.5-fold) and decreased to control levels in the E2 group. RVF resulted in elevated Akt phosphorylation, but not ERK, in the RV, and E2 therapy restored Akt phosphorylation. In conclusion, E2 therapy reverses adverse RV remodeling associated with PH by reversing fibrosis and upregulation of novel ECM enzymes ADAM15, ADAM17, and OPN. These effects are likely mediated through estrogen receptor-β. PMID:22628376

Who is at risk of death from nephrectomy? An analysis of thirty-day mortality after 21 380 nephrectomies in 3 years of the British Association of Urological Surgeons (BAUS) National Nephrectomy Audit.

PubMed

Fernando, Archie; Fowler, Sarah; Van Hemelrijck, Mieke; O'Brien, Tim

2017-09-01

To ascertain contemporary overall and differential thirty-day mortality (TDM) rates after all types of nephrectomy in the UK, and to identify potential new risk factors for death. We conducted a retrospective analysis of the 110 deaths that occurred within 30 days of surgery out of the total of 21 380 nephrectomies performed, and calculated the odds ratio (OR) and 95% confidence interval (CI) for TDM based on peri-operative characteristics. The overall TDM rate was 110/21380 (0.5%). The TDM rates after radical, partial, simple nephrectomy and nephro-ureterectomy were 0.6% (63/11057), 0.1% (4/3931), 0.4% (11/2819) and 0.9% (28/3091), respectively. TDM increased with age, stage, estimated blood loss (EBL), operating time and performance status. EBL of 1-2 L was associated with a greater risk of TDM than EBL of 2-5 L (OR 1.38; 95% CI 1.03-2.24). Conversion from minimally invasive surgery was associated with higher risk than non-conversion (OR 2.53; 95% CI 1.14-4.51. Curative surgery was safer than cytoreductive surgery (OR 0.31; 95% CI 0.18-0.54). There was an association between surgical volume and TDM. This study provides contemporary insights into the true risks of all types of nephrectomy. The TDM rate after nephrectomy in the UK appears acceptably low at 0.5%. Established risk factors were confirmed and the following novel risk factors were identified: modest EBL (1-2 L) and conversion from minimally invasive surgery. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

OpnS, an Outer Membrane Porin of Xenorhabdus nematophila, Confers a Competitive Advantage for Growth in the Insect Host▿ †

PubMed Central

van der Hoeven, Ransome; Forst, Steven

2009-01-01

The gammaproteobacterium Xenorhabdus nematophila engages in a mutualistic association with an entomopathogenic nematode and also functions as a pathogen toward different insect hosts. We studied the role of the growth-phase-regulated outer membrane protein OpnS in host interactions. OpnS was shown to be a 16-stranded β-barrel porin. opnS was expressed during growth in insect hemolymph and expression was elevated as the cell density increased. When wild-type and opnS deletion strains were coinjected into insects, the wild-type strain was predominantly recovered from the insect cadaver. Similarly, an opnS-complemented strain outcompeted the ΔopnS strain. Coinjection of the wild-type and ΔopnS strains together with uncolonized nematodes into insects resulted in nematode progeny that were almost exclusively colonized with the wild-type strain. Likewise, nematode progeny recovered after coinjection of a mixture of nematodes carrying either the wild-type or ΔopnS strain were colonized by the wild-type strain. In addition, the ΔopnS strain displayed a competitive growth defect when grown together with the wild-type strain in insect hemolymph but not in defined culture medium. The ΔopnS strain displayed increased sensitivity to antimicrobial compounds, suggesting that deletion of OpnS affected the integrity of the outer membrane. These findings show that the OpnS porin confers a competitive advantage for the growth and/or the survival of X. nematophila in the insect host and provides a new model for studying the biological relevance of differential regulation of porins in a natural host environment. PMID:19465651

Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions.

PubMed

Wine, Eytan; Shen-Tu, Grace; Gareau, Mélanie G; Goldberg, Harvey A; Licht, Christoph; Ngan, Bo-Yee; Sorensen, Esben S; Greenaway, James; Sodek, Jaro; Zohar, Ron; Sherman, Philip M

2010-09-01

Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN(+/+) and OPN(-/-) fibroblasts were incubated with C. rodentium and attaching-effacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN(-/-) mice, and spleen enlargement by infection was absent in OPN(-/-) mice. Rectal administration of OPN to OPN(-/-) mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN(-/-) mice, compared with wild-type mice, which was accompanied by reduced attaching-effacing lesions, both in infected OPN(-/-) mice and OPN(-/-) mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN(-/-) cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.

Premalignant lesions in the kidney.

PubMed

Kirkali, Z; Yorukoglu, K

2001-12-07

Renal cell carcinoma (RCC) is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN) is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1) morphological similarity; (2) spatial association; (3) development of microinvasive carcinoma; (4) higher frequency, severity, and extent then invasive carcinoma; (5) progression to invasive cancer; and (6) similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered.

Peritumoral Artery Scoring System: a Novel Scoring System to Predict Renal Function Outcome after Laparoscopic Partial Nephrectomy.

PubMed

Zhang, Ruiyun; Wu, Guangyu; Huang, Jiwei; Shi, Oumin; Kong, Wen; Chen, Yonghui; Xu, Jianrong; Xue, Wei; Zhang, Jin; Huang, Yiran

2017-06-06

The present study aimed to assess the impact of peritumoral artery characteristics on renal function outcome prediction using a novel Peritumoral Artery Scoring System based on computed tomography arteriography. Peritumoral artery characteristics and renal function were evaluated in 220 patients who underwent laparoscopic partial nephrectomy and then validate in 51 patients with split and total glomerular filtration rate (GFR). In particular, peritumoral artery classification and diameter were measured to assign arteries into low, moderate, and high Peritumoral Artery Scoring System risk categories. Univariable and multivariable logistic regression analyses were then used to determine risk factors for major renal functional decline. The Peritumoral Artery Scoring System and four other nephrometry systems were compared using receiver operating characteristic curve analysis. The Peritumoral Artery Scoring System was significantly superior to the other systems for predicting postoperative renal function decline (p < 0.001). In receiver operating characteristic analysis, our category system was a superior independent predictor of estimated glomerular filtration rate (eGFR) decline (area-under-the-curve = 0.865, p < 0.001) and total GFR decline (area-under-the-curve = 0.796, p < 0.001), and split GFR decline (area-under-the-curve = 0.841, p < 0.001). Peritumoral artery characteristics were independent predictors of renal function outcome after laparoscopic partial nephrectomy.

An Ultrasonic Clamp for Bloodless Partial Nephrectomy

NASA Astrophysics Data System (ADS)

Lafon, Cyril; Bouchoux, Guillaume; Murat, François Joseph; Birer, Alain; Theillère, Yves; Chapelon, Jean Yves; Cathignol, Dominique

2007-05-01

Maximum conservation of the kidney is preferable through partial nephrectomy for patients at risk of disease recurrence of renal cancers. Haemostatic tools are needed in order to achieve bloodless surgery and reduce post surgery morbidity. Two piezo-ceramic transducers operating at a frequency of 4 MHz were mounted on each arm of a clamp. When used for coagulation purposes, two transducers situated on opposite arms of the clamp were driven simultaneously. Heat delivery was optimized as each transducers mirrored back to targeted tissues the wave generated by the opposite transducer. Real-time treatment monitoring with an echo-based technique was also envisaged with this clamp. Therapy was periodically interrupted so one transducer could generate a pulse. The echo returning from the opposite transducer was treated. Coagulation necroses were obtained in vitro on substantial thicknesses (23-38mm) of pig liver over exposure durations ranging from 30s to 130s, and with acoustic intensities of less than 15W/cm2 per transducer. Both kidneys of two pigs were treated in vivo with the clamp (14.5W/cm2 for 90s), and the partial nephrectomies performed proved to be bloodless. In vitro and in vivo, wide transfixing lesions corresponded to an echo energy decrease superior to -10dB and parabolic form of the time of flight versus treatment time. In conclusion, this ultrasound clamp has proven to be an excellent mean for achieving monitored haemostasis in kidney.

Particularly interesting Cys-His-rich protein is highly expressed in human intracranial aneurysms and resists aneurysmal rupture

PubMed Central

Peng, Yu-Tao; Shi, Xiang-En; Li, Zhi-Qiang; He, Xin; Sun, Yu-Ming

2016-01-01

Particularly interesting Cys-His-rich protein (PINCH) has several biological functions in cancer development, invasion and metastasis in malignant cells, and the expression of PINCH is upregulated in several cancer types, including breast cancer, gastric adenocarcinoma and rectal cancer. However, the contribution of PINCH to human cerebral aneurysms remains largely unknown. Therefore, the significance of PINCH expression in cerebral aneurysm growth and rupture was examined in the present study. The protein expression levels of alpha-smooth muscle actin, osteopontin (OPN), matrix metalloproteinase (MMP) 9 and PINCH were evaluated using immunohistochemistry and western blot analyses. The results demonstrate that the protein expression levels of OPN, MMP9 and PINCH in the unruptured intracranial aneurysm (UA) and ruptured intracranial aneurysm (RA) groups were markedly higher than those of the control group, whereas OPN and PINCH expression levels were decreased in the RA group compared to those of the UA group. In addition, there was a strong correlation between PINCH and tumor size (r=0.650 and P=0.0026), as well as between PINCH and OPN (r=0.639 and P=0.0033) in the unruptured cerebral aneurysms. However, the correlation between PINCH and tumor size (r=0.450 and P=0.1393) and between PINCH and OPN (r=0.366 and P=0.2426) revealed no obvious difference in the ruptured cerebral aneurysms. In conclusion, PINCH was highly expressed in the UAs, which may be a critical factor for preventing aneurysmal rupture. Moreover, PINCH may facilitate intracranial aneurysm progression, at least partially, through the activation of extracellular signal-regulated kinase signaling and the suppression of c-Jun N-terminal kinase signaling. PMID:28101173

Particularly interesting Cys-His-rich protein is highly expressed in human intracranial aneurysms and resists aneurysmal rupture.

PubMed

Peng, Yu-Tao; Shi, Xiang-En; Li, Zhi-Qiang; He, Xin; Sun, Yu-Ming

2016-12-01

Particularly interesting Cys-His-rich protein (PINCH) has several biological functions in cancer development, invasion and metastasis in malignant cells, and the expression of PINCH is upregulated in several cancer types, including breast cancer, gastric adenocarcinoma and rectal cancer. However, the contribution of PINCH to human cerebral aneurysms remains largely unknown. Therefore, the significance of PINCH expression in cerebral aneurysm growth and rupture was examined in the present study. The protein expression levels of alpha-smooth muscle actin, osteopontin (OPN), matrix metalloproteinase (MMP) 9 and PINCH were evaluated using immunohistochemistry and western blot analyses. The results demonstrate that the protein expression levels of OPN, MMP9 and PINCH in the unruptured intracranial aneurysm (UA) and ruptured intracranial aneurysm (RA) groups were markedly higher than those of the control group, whereas OPN and PINCH expression levels were decreased in the RA group compared to those of the UA group. In addition, there was a strong correlation between PINCH and tumor size ( r =0.650 and P=0.0026), as well as between PINCH and OPN ( r =0.639 and P=0.0033) in the unruptured cerebral aneurysms. However, the correlation between PINCH and tumor size ( r =0.450 and P=0.1393) and between PINCH and OPN ( r =0.366 and P=0.2426) revealed no obvious difference in the ruptured cerebral aneurysms. In conclusion, PINCH was highly expressed in the UAs, which may be a critical factor for preventing aneurysmal rupture. Moreover, PINCH may facilitate intracranial aneurysm progression, at least partially, through the activation of extracellular signal-regulated kinase signaling and the suppression of c-Jun N-terminal kinase signaling.

Dissociation of eye and head components of gaze shifts by stimulation of the omnipause neuron region.

PubMed

Gandhi, Neeraj J; Sparks, David L

2007-07-01

Natural movements often include actions integrated across multiple effectors. Coordinated eye-head movements are driven by a command to shift the line of sight by a desired displacement vector. Yet because extraocular and neck motoneurons are separate entities, the gaze shift command must be separated into independent signals for eye and head movement control. We report that this separation occurs, at least partially, at or before the level of pontine omnipause neurons (OPNs). Stimulation of the OPNs prior to and during gaze shifts temporally decoupled the eye and head components by inhibiting gaze and eye saccades. In contrast, head movements were consistently initiated before gaze onset, and ongoing head movements continued along their trajectories, albeit with some characteristic modulations. After stimulation offset, a gaze shift composed of an eye saccade, and a reaccelerated head movement was produced to preserve gaze accuracy. We conclude that signals subject to OPN inhibition produce the eye-movement component of a coordinated eye-head gaze shift and are not the only signals involved in the generation of the head component of the gaze shift.

Impact of Renal Hilar Control on Outcomes of Robotic Partial Nephrectomy: Systematic Review and Cumulative Meta-analysis.

PubMed

Cacciamani, Giovanni E; Medina, Luis G; Gill, Tania S; Mendelsohn, Alec; Husain, Fatima; Bhardwaj, Lokesh; Artibani, Walter; Sotelo, Renè; Gill, Inderbir S

2018-02-05

During robotic partial nephrectomy (RPN), various techniques of hilar control have been described, including on-clamp, early unclamping, selective/super-selective clamping, and completely-unclamped RPN. To evaluate the impact of various hilar control techniques on perioperative, functional, and oncological outcomes of RPN for tumors. We conducted a systematic literature review and meta-analysis of all comparative studies on various hilar control techniques during RPN using PubMed, Scopus, and Web of Science according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement, and Methods and Guide for Effectiveness and Comparative Effectiveness Review of the Agency for Healthcare Research and Quality. Cumulative meta-analysis of comparative studies was conducted using Review Manager 5.3. Of 987 RPN publications in the literature, 19 qualified for this analysis. Comparison of off-clamp versus on-clamp RPN (n=9), selective clamping versus on-clamp RPN (n=3), super selective clamping versus on-clamp RPN (n=5), and early unclamped versus on-clamp (n=3) were reported. Patients undergoing RPN using off-clamp, selective/super selective, or early unclamp techniques had higher estimated blood loss compared with on-clamp RPN (weight mean difference [WMD]: 47.83, p=0.000, WMD: 41.06, p=0.02, and WMD: 37.50, p=0.47); however, this did not seem clinically relevant, since transfusion rates were similar (odds ratio [OR]: 0.98, p=0.95, OR: 0.72, p=0.7, and OR: 1.36, p=0.33, respectively). All groups appeared similar with regards to hospital stay, transfusions, overall and major complications, and positive cancer margin rates. Short- and long-term renal functional outcomes appeared superior in the off-clamp and super selective clamp groups compared with the on-clamp RPN cohort. Off-clamp, selective/super selective clamp, and early unclamp hilar control techniques are safe and feasible approaches for RPN surgery, with similar perioperative and oncological outcomes compared with on-clamp RPN. Minimizing global renal ischemia may provide superior renal function preservation. However, higher quality data are necessary for definitive conclusions in this regard. The objective of partial nephrectomy is to treat the cancer while maximizing renal function preservation. Clamping the main vessels is done primarily to reduce the blood loss during partial nephrectomy; however, vascular clamping can compromise kidney function. In order to avoid clamping, various techniques have been described. Our analysis showed that techniques that avoid main renal artery clamping during RPN are associated with better renal function preservation, yet deliver non-inferior perioperative and oncological outcomes as compared with robotic partial nephrectomy procedures that clamp the main vessels. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Impact of Host Factors on Robotic Partial Nephrectomy Outcomes: Comprehensive Systematic Review and Meta-analysis.

PubMed

Cacciamani, Giovanni; Gill, Tania S; Medina, Luis; Ashrafi, Akbar; Winter, Matthew; Sotelo, Renè; Artibani, Walter; Gill, Inderbir

2018-05-03

Host factors (tumor size/complexity, patient comorbidities) impact outcomes of robotic partial nephrectomy (RPN). We report a comprehensive systematic review and meta-analysis to critically evaluate impact of host factors on operative, peri-operative, functional, oncological and survival outcomes of RPN. All full-text English-language publications on RPN comparing host factors were evaluated. We followed Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement and Agency for Healthcare Research and Quality (AHRQ) guidelines to evaluate Pubmed®, Scopus® and Web of Science® (01/01/2000-31/06/2017). Weighted mean difference (WMD) and odds ratio (OR) compared continuous and dichotomous variables, respectively. Sensitivity analyses were performed as needed. To condense the sheer volume of analyses, data are presented using novel summary forest plots. PROSPERO registration number CRD42017062712. Our meta-analysis evaluated 41 papers including 10,506 patients. Tumor factors: Compared to patients with complex tumors, those with non-complex tumors had lesser OR-time (WMD: -44.95; p=0.003), EBL (WMD: -160; p< 0.003), warm ischemia time (WIT) (WMD:-8.56 ; p≤ 0.00001) and post-operative complications (OR:0.42; p=0.01). Tumors > 4 cm were associated with higher OR-time (WMD: 30.11; p≤ 0.00001), EBL (WMD: 39.26, 95% CI 28.77, 49.74; p≤ 0.00001), WIT (WMD: 5.17; p≤ 0.00001), transfusions (OR: 3.15; p=0.003), postoperative complications (OR:1.88; p=0.004) and LOS (WMD:0.56; p=0.0004). Hilar tumors reported greater EBL (WMD:51.34; p=0.03), WIT (WMD: 8.17; p≤ 0.00001) and conversion to OPN (OR: 14.14; p=0.006). Tumor location, anterior versus posterior, did not impact RPN outcomes. Patient factors: Older patients (> 70 years) trended non-significantly towards greater %eGFR decrease and overall mortality. Abnormal BMI cohort reported greater OR-time (WMD:13.47; p<0.001), EBL(WMD:45.44; p<0.0001) and postoperative complications (OR:1.48; p=0.03). CKD cohort had lesser reduction in post-operative % eGFR (WMD:7.16; 95% CI 2.74, 11.59; p=0.002) and increased postoperative complications (OR: 2.05; 95% CI 1.47, 2.85). RPN outcomes are impacted by host factors, including tumor and patient characteristics. Awareness of this increased risk, and its mitigation with expert patient selection, is important for excellent RPN outcomes. Our meta-analysis provides comprehensive, objective, summary data of 10,506 patients, detailing discreet outcomes for discreet host factors, to better inform urologists and patients considering RPN surgery. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Adjuvant Everolimus for Resected Kidney Cancer

Cancer.gov

In this clinical trial, patients with renal cell cancer who have undergone partial or complete nephrectomy will be randomly assigned to take everolimus tablets or matching placebo tablets daily for 54 weeks.

Surgery Videos: MedlinePlus

MedlinePlus Videos and Cool Tools

... 2009) Mitral Valve Prolapse Minimally Invasive Heart Surgery: Robot Assisted Mitral Valve Repair (Baptist Health South Florida, ... Center, Merriam, KS, 05/04/2012) Kidney Cancer Robot Assisted Partial Nephrectomy Using Fluorescence (Shawnee Mission Medical ...

Prognostic impact of mRNA levels of osteopontin splice variants in soft tissue sarcoma patients.

PubMed

Hahnel, Antje; Wichmann, Henri; Greither, Thomas; Kappler, Matthias; Würl, Peter; Kotzsch, Matthias; Taubert, Helge; Vordermark, Dirk; Bache, Matthias

2012-04-02

It is well known that osteopontin (OPN) plays an important role in tumor progression and that a high OPN expression level in several tumor entities correlates with poor prognosis in cancer patients. However, little is known about the prognostic relevance of the OPN mRNA splice variants. We analyzed the mRNA expression levels of different OPN splice variants in tumor tissue of 124 soft tissue sarcoma (STS) patients. Quantitative real-time PCR (qRT-PCR) was used to analyze the mRNA expression level of three OPN splice variants (OPN-a, -b and -c). The multivariate Cox's proportional hazard regression model revealed that high mRNA expression levels of OPN splice variants are significantly associated with poor prognosis in STS patients (n = 124). Women (n = 68) with high mRNA expression levels of OPN-a and OPN-b have an especially elevated risk of tumor-related death (OPN-a: RR = 3.0, P = 0.01, CI = 1.3-6.8; OPN-b: RR = 3.4, P = 0.01, CI = 1.4-8.2). In particular, we found that high mRNA expression levels of OPN-b and OPN-c correlated with a high risk of tumor-related death in STS patients that received radiotherapy (n = 52; OPN-b: RR = 10.3, P < 0.01, CI = 2.0-53.7; OPN-c: RR = 11.4, P < 0.01, CI = 2.2-59.3). Our study shows that elevated mRNA expression levels of OPN splice variants are negative prognostic and predictive markers for STS patients. Further studies are needed to clarify the impact of the OPN splice variants on prognosis.

Obesity, hypertension and diabetes mellitus affect complication rate of different nephrectomy techniques.

PubMed

Hua, X; Ying-Ying, C; Zu-Jun, F; Gang, X; Zu-Quan, X; Qiang, D; Hao-Wen, J

2014-12-01

To investigate whether obesity, hypertension, and diabetes mellitus (DM) would increase post-nephrectomy complication rates using standardized classification method. We retrospectively included 843 patients from March 2006 to November 2012, of whom 613 underwent radical nephrectomy (RN) and 229 had partial nephrectomy (PN). Modified Clavien classification system was applied to quantify complication severity of nephrectomy. Fisher's exact or chi-square test was used to assess the relationship between complication rates and obesity, hypertension, as well as DM. The prevalence of obesity, hypertension, and DM was 11.51%, 30.84%, 8.78%, respectively. The overall complication rate was 19.31%, 30.04%, 35.71% and 36.36% for laparoscopic radical nephrectomy (LRN), open-RN, LPN and open-PN respectively. An increasing trend of low grade complication rate as BMI increased was observed in LRN (P=.027) and open-RN (P<.001). Obese patients had greater chance to have low grade complications in LRN (OR=4.471; 95% CI: 1.290-17.422; P=0.031) and open-RN (OR=2.448; 95% CI: 1.703-3.518; P<.001). Patients with hypertension were more likely to have low grade complications, especially grade ii complications in open-RN (OR=1.526; 95% CI: 1.055-2.206; P=.026) and open PN (OR=2.032; 95% CI: 1.199-3.443; P=.009). DM was also associated with higher grade i complication rate in open-RN (OR=2.490; 95% CI: 331-4.657; P=.016) and open-PN (OR=4.425; 95% CI: 1.815-10.791; P=.013). High grade complication rates were similar in comparison. Obesity, hypertension, and DM were closely associated with increased post-nephrectomy complication rates, mainly low grade complications. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

THE EFFECT OF TOTAL AND PARTIAL NEPHRECTOMY ON THE PHARMACOKINETICS OF INTRAVENOUS PARACETAMOL IN HUMANS.

PubMed

Karbownik, Agnieszka; Polom, Wojciech; Porazka, Joanna; Szalek, Edyta; Grabowski, Tomasz; Wolc, Anna; Matuszewski Marcin; Grzesowiak, Edmund

2017-05-01

Paracetamol is one of the most common analgesic and antipyretic drugs. Recently intravenous paracetamol has been widely used to treat moderate postoperative pain. Surgery is the main method of treatment of renal cancer. Total or partial nephrectomy can be performed, depending on the size and location of the tumor. Pharmacokinetics of drugs may depend on the type of surgery. The aim of the study was to compare the postinfusion pharmacokinetics of paracetamol in patients after total nephrectomy (TN) and nephron sparing surgery (NSS).The research was carried out on two groups of patients after nephrectomy: total (TN n = 37; mean [SD], age, 60.4 [10.9] years; BMI, 26.5 [3.8] kg/m2; creatinine clearance, Cl, 80.9 [37.1] mL/min) and nephron sparing surgery (NSS n = 17; 57.9 [16.5] years; BMI, 29.5 [5.3] kg/m2; Cl, 97.6 [27.8] mL/min). The patients were treated with paracetamol (PerfalganO Bristol-Myers Squibb) at an intravenous dose of 1.000 mg, which was infused for 15 minutes after surgery. The concentrations of paracetamol in the patients' plasma were determined by the HPLC method with UV detection (X = 261 run). The main pharmacokinetic parameters of paracetamol in the TN vs. NSS group were as follows: C.. 29.08 [17.39] vs. 27.54 [15.70] pg/mL (p = 0.6692); AUC5, 29.24 [13.86] vs. 34.85 [14.28] pg.h/mL (p = 0.2896); AUMC5,,,, 47.58 [26.08] vs. 62.02 [27.64] pg-h/mL (p = 0.1345); to. 2.34 [0.96] vs. 1.93 [0.50] h (p = 0.1415), respectively. In both groups the exposure to paracetamol was comparable. The t1/2 after nephron sparing surgery was shorter than after total nephrectomy. Therefore, these patients may demand more frequent drug administration. In the NSS group the C. of the analgesic was considerably reduced in men.

Effects of osteopontin inhibition on radiosensitivity of MDA-MB-231 breast cancer cells.

PubMed

Hahnel, Antje; Wichmann, Henri; Kappler, Matthias; Kotzsch, Matthias; Vordermark, Dirk; Taubert, Helge; Bache, Matthias

2010-09-17

Osteopontin (OPN) is a secreted glycophosphoprotein that is overexpressed in various tumors, and high levels of OPN have been associated with poor prognosis of cancer patients. In patients with head and neck cancer, high OPN plasma levels have been associated with poor prognosis following radiotherapy. Since little is known about the relationship between OPN expression and radiosensitivity, we investigated the cellular and radiation induced effects of OPN siRNA in human MDA-MB-231 breast cancer cells. MDA-MB-231 cells were transfected with OPN-specific siRNAs and irradiated after 24 h. To verify the OPN knockdown, we measured the OPN mRNA and protein levels using qRT-PCR and Western blot analysis. Furthermore, the functional effects of OPN siRNAs were studied by assays to assess clonogenic survival, migration and induction of apoptosis. Treatment of MDA-MB-231 cells with OPN siRNAs resulted in an 80% decrease in the OPN mRNA level and in a decrease in extracellular OPN protein level. Transfection reduced clonogenic survival to 42% (p = 0.008), decreased the migration rate to 60% (p = 0.15) and increased apoptosis from 0.3% to 1.7% (p = 0.04). Combination of OPN siRNA and irradiation at 2 Gy resulted in a further reduction of clonogenic survival to 27% (p < 0.001), decreased the migration rate to 40% (p = 0.03) and increased apoptosis to 4% (p < 0.005). Furthermore, OPN knockdown caused a weak radiosensitization with an enhancement factor of 1.5 at 6 Gy (p = 0.09) and a dose modifying factor (DMF10) of 1.1. Our results suggest that an OPN knockdown improves radiobiological effects in MDA-MB-231 cells. Therefore, OPN seems to be an attractive target to improve the effectiveness of radiotherapy.

Intraoperative ultrasound control of surgical margins during partial nephrectomy.

PubMed

Alharbi, Feras M; Chahwan, Charles K; Le Gal, Sophie G; Guleryuz, Kerem M; Tillou, Xavier P; Doerfler, Arnaud P

2016-01-01

To evaluate a simple and fast technique to ensure negative surgical margins on partial nephrectomies, while correlating margin statuses with the final pathology report. This study was conducted for patients undergoing partial nephrectomy (PN) with T1-T2 renal tumors from January 2010 to the end of December 2015. Before tumor removal, intraoperative ultrasound (US) localization was performed. After tumor removal and before performing hemostasis of the kidney, the specimens were placed in a saline solution and a US was performed to evaluate if the tumor's capsule were intact, and then compared to the final pathology results. In 177 PN(s) (147 open procedures and 30 laparoscopic procedures) were performed on 147 patients. Arterial clamping was done for 32 patients and the mean warm ischemia time was 19 ± 6 min. The mean US examination time was 41 ± 7 s. The US analysis of surgical margins was negative in 172 cases, positive in four, and in only one case it was not possible to conclude. The final pathology results revealed one false positive surgical margin and one false negative surgical margin, while all other margins were in concert with US results. The mean tumor size was 3.53 ± 1.43 cm, and the mean surgical margin was 2.8 ± 1.5 mm. The intraoperative US control of resection margins in PN is a simple, efficient, and effective method for ensuring negative surgical margins with a small increase in warm ischemia time and can be conducted by the operating urologist.

Robotic assisted laparoscopic partial nephrectomy using contrast‐enhanced ultrasound scan to map renal blood flow

PubMed Central

Motiwala, Aamir; Eves, Susannah; Gray, Rob; Thomas, Asha; Meiers, Isabelle; Sharif, Haytham; Motiwala, Hanif; Laniado, Marc; Karim, Omer

2016-01-01

Abstract Objective The paper describes novel real‐time ‘in situ mapping’ and ‘sequential occlusion angiography’ to facilitate selective ischaemia robotic partial nephrectomy (RPN) using intraoperative contrast enhanced ultrasound scan (CEUS). Materials and methods Data were collected and assessed for 60 patients (61 tumours) between 2009 and 2013. 31 (50.8%) tumours underwent ‘Global Ischaemia’, 27 (44.3%) underwent ‘Selective Ischaemia’ and 3 (4.9%) were removed ‘Off Clamp Zero Ischaemia’. Demographics, operative variables, complications, renal pathology and outcomes were assessed. Results Median PADUA score was 9 (range 7–10). The mean warm ischaemia time in selective ischaemia was less and statistically significant than in global ischaemia (17.1 and 21.4, respectively). Mean operative time was 163 min. Postoperative complications (n = 10) included three (5%) Clavien grade 3 or above. Malignancy was demonstrated in 47 (77%) with negative margin in 43 (91.5%) and positive margin in four (8.5%). Long‐term decrease in eGFR post selective ischaemia robotic partial nephrectomy was less compared with global ischaemia (four and eight, respectively) but not statistically significant. Conclusions This technique is safe, feasible and cost‐effective with comparable perioperative outcomes. The technical aspects elucidate the role of intraoperative CEUS to facilitate and ascertain selective ischaemia. Further work is required to demonstrate long‐term oncological outcomes. © 2016 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons, Ltd. PMID:26948671

Upper urinary tract laparoendoscopic single-site surgery based on a novel cost-effective reusable platform.

PubMed

Schwentner, Christian; Todenhöfer, Tilman; Seibold, Joerg; Alloussi, Saladin H; Aufderklamm, Stefan; Mischinger, Johannes; Germann, Miriam; Stenzl, Arnulf; Gakis, Georgios

2013-02-01

Several disposable platforms have been introduced for laparoendoscopic single-site (LESS) surgery. Besides technical issues, cost is one of the main limiting factors for their widespread use. We present our experience with LESS surgery for kidney pathologies using the first completely reusable LESS platform. We performed LESS kidney procedures in 29 patients including nephrectomy (18), partial nephrectomy (3), pyeloplasty (4), and renal cyst ablation (4). All procedures were performed using a completely reusable single-port device (X-Cone) with a simplified combination of standard and prebent instruments. We obtained perioperative and demographic data including a visual analog pain scale (VAS); complications were recorded using Clavien grading. Mean patient age was 49.31 years. Conversion to standard laparoscopy was necessary in one and addition of a needlescopic instrument in four cases. No open conversion was necessary. Intra- and postoperative complications occurred in two (Clavien II) cases. Mean operative time was 110, 90, and 89 minutes, and hospital stay was 4.9, 3.1, and 3.6 days for nephrectomy, partial nephrectomy, and pyeloplasty, respectively. Mean VAS was 2.13, 1.67, and 1.5 while blood loss was 81.3 mL, 140 mL, and 17.5 mL, respectively. There were no positive resection margins. LESS with a completely reusable platform is feasible for different upper urinary tract procedures yielding favorable functional and cosmetic results. A simplified combination of standard straight instruments and a single prebent grasper facilitates handling and shortens the learning curve. Reusable materials significantly reduce cost and may help to further adopt LESS surgery in surgical practice.

OpnS, an outer membrane porin of Xenorhabdus nematophila, confers a competitive advantage for growth in the insect host.

PubMed

van der Hoeven, Ransome; Forst, Steven

2009-09-01

The gammaproteobacterium Xenorhabdus nematophila engages in a mutualistic association with an entomopathogenic nematode and also functions as a pathogen toward different insect hosts. We studied the role of the growth-phase-regulated outer membrane protein OpnS in host interactions. OpnS was shown to be a 16-stranded beta-barrel porin. opnS was expressed during growth in insect hemolymph and expression was elevated as the cell density increased. When wild-type and opnS deletion strains were coinjected into insects, the wild-type strain was predominantly recovered from the insect cadaver. Similarly, an opnS-complemented strain outcompeted the DeltaopnS strain. Coinjection of the wild-type and DeltaopnS strains together with uncolonized nematodes into insects resulted in nematode progeny that were almost exclusively colonized with the wild-type strain. Likewise, nematode progeny recovered after coinjection of a mixture of nematodes carrying either the wild-type or DeltaopnS strain were colonized by the wild-type strain. In addition, the DeltaopnS strain displayed a competitive growth defect when grown together with the wild-type strain in insect hemolymph but not in defined culture medium. The DeltaopnS strain displayed increased sensitivity to antimicrobial compounds, suggesting that deletion of OpnS affected the integrity of the outer membrane. These findings show that the OpnS porin confers a competitive advantage for the growth and/or the survival of X. nematophila in the insect host and provides a new model for studying the biological relevance of differential regulation of porins in a natural host environment.

Association of the osteopontin rs1126616 polymorphism and a higher serum osteopontin level with lupus nephritis

PubMed Central

SALIMI, SAEEDEH; NOORA, MEHRANGIZ; NABIZADEH, SIMA; REZAEI, MAHNAZ; SHAHRAKI, HOSSAIN; MILAD, MOHAMMADOO-KHORASSANI; NAGHAVI, ANOOSH; FARAJIAN-MASHHADI, FARZANEH; ZAKERI, ZAHRA; SANDOUGHI, MAHNAZ

2016-01-01

Osteopontin (OPN) is a chemokine-like glycoprotein that has a prominent role in regulating inflammation and immunity. OPN polymorphisms and elevated OPN levels are associated with systemic lupus erythematosus (SLE) in several populations. The aim of present study was to evaluate the association between the OPN rs1126616 polymorphism and OPN level with SLE susceptibility. A total of 163 SLE patients and 180 age-, gender- and ethnically matched controls were genotyped for the rs1126616 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism method. Serum OPN levels were assayed by the enzyme-linked immunosorbent assay. There was no association between the OPN rs1126616 C/T polymorphism and SLE. The frequency of the OPN rs1126616 CT genotype was significantly higher in SLE patients with nephritis compared to SLE patients without nephritis and controls. Additionally, the frequency of TT genotypes was higher in SLE patients with nephritis compared to controls. The serum OPN levels were significantly higher in SLE patients compared to controls (50.6±22 vs. 35.6±15.8 ng/ml, P<0.001). Increased serum OPN levels were observed in SLE patients with lupus nephritis and joint symptoms. There was no correlation between OPN levels and the OPN rs1126616 polymorphism. The present data suggest that the CT and TT genotypes of the OPN rs1126616 polymorphism could be a risk factor for lupus nephritis. The OPN level is associated with SLE and certain SLE manifestations. However, there was no association between the OPN rs1126616 C/T polymorphism and SLE susceptibility. PMID:26998275

Antigen-Specific Induction of Osteopontin Contributes to the Chronification of Allergic Contact Dermatitis

PubMed Central

Seier, Anne M.; Renkl, Andreas C.; Schulz, Guido; Uebele, Tanja; Sindrilaru, Anca; Iben, Sebastian; Liaw, Lucy; Kon, Shigeyuki; Uede, Toshimitsu; Weiss, Johannes M.

2010-01-01

Allergic contact dermatitis is a T cell-mediated immune response, which in its relapsing chronic form is of high socioeconomic impact. The phosphoglycoprotein osteopontin (OPN) has chemotactic and Th1 cytokine functions and in various models is essential for robust T cell-mediated immunity. Here we demonstrate that OPN is abundantly expressed by both effector T cells and keratinocytes in allergic contact dermatitis lesions. T cells from nickel-allergic donors secrete high levels of OPN following antigen-specific stimulation. OPN may substitute for missing IFN-γ secretion in T effector cells because low IFN-γ-producing T cell clones secrete high levels of OPN, and OPN down-modulates their interleukin-4 expression. Furthermore, interferon-γ from T effector cells augments OPN in allergic contact dermatitis by inducing OPN in keratinocytes, which in turn polarizes dendritic cells and attracts inflammatory cells. In the murine contact hypersensitivity (CHS) model for allergic contact dermatitis, OPN is strongly induced in antigen-specific proliferating T cells, and OPN null mice display a reduced chronic CHS inflammatory response due to a decreased influx of effector T cells. Importantly, because of its function for chronic allergic contact dermatitis, OPN may well be a therapeutic target, because anti-OPN antibody treatment in part suppresses established chronic CHS. PMID:20008129

Association between osteopontin and human abdominal aortic aneurysm.

PubMed

Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E

2007-03-01

In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion. Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.

Elevated Expression of Osteopontin May Be Related to Adipose Tissue Macrophage Accumulation and Liver Steatosis in Morbid Obesity

PubMed Central

Bertola, Adeline; Deveaux, Vanessa; Bonnafous, Stéphanie; Rousseau, Déborah; Anty, Rodolphe; Wakkach, Abdelilah; Dahman, Moncef; Tordjman, Joan; Clément, Karine; McQuaid, Siobhán E.; Frayn, Keith N.; Huet, Pierre-Michel; Gugenheim, Jean; Lotersztajn, Sophie; Le Marchand-Brustel, Yannick; Tran, Albert; Gual, Philippe

2009-01-01

OBJECTIVE—Osteopontin (OPN) plays an important role in the development of insulin resistance and liver complications in dietary murine models. We aimed to determine the expression pattern of OPN and its receptor CD44 in obese patients and mice according to insulin resistance and liver steatosis. RESEARCH DESIGN AND METHODS—OPN and CD44 expressions were studied in 52 morbidly obese patients and in mice. Cellular studies were performed in HepG2 cells. RESULTS—Hepatic OPN and CD44 expressions were strongly correlated with liver steatosis and insulin resistance in obese patients and mice. This increased OPN expression could be due to the accumulation of triglycerides, since fat loading in HepG2 promotes OPN expression. In contrast, OPN expression in adipose tissue (AT) was enhanced independently of insulin resistance and hepatic steatosis in obese patients. The elevated OPN expression in AT was paralleled with the AT macrophage infiltration, and both phenomena were reversed after weight loss. The circulating OPN level was slightly elevated in obese patients and was not related to liver steatosis. Further, AT did not appear to secrete OPN. In contrast, bariatric surgery–induced weight loss induced a strong increase in circulating OPN. CONCLUSIONS—The modestly elevated circulating OPN levels in morbidly obese patients were not related to liver steatosis and did not appear to result from adipose tissue secretion. In subcutaneous AT, expression of OPN was directly related to macrophage accumulation independently from liver complications. In contrast, hepatic OPN and CD44 expressions were related to insulin resistance and steatosis, suggesting their local implication in the progression of liver injury. PMID:18952835

Osteopontin inhibits osteoblast responsiveness through the down-regulation of focal adhesion kinase mediated by the induction of low-molecular weight protein tyrosine phosphatase.

PubMed

Kusuyama, Joji; Bandow, Kenjiro; Ohnishi, Tomokazu; Hisadome, Mitsuhiro; Shima, Kaori; Semba, Ichiro; Matsuguchi, Tetsuya

2017-05-15

Osteopontin (OPN) is an osteogenic marker protein. Osteoblast functions are affected by inflammatory cytokines and pathological conditions. OPN is highly expressed in bone lesions such as those in rheumatoid arthritis. However, local regulatory effects of OPN on osteoblasts remain ambiguous. Here we examined how OPN influences osteoblast responses to mechanical stress and growth factors. Expression of NO synthase 1 ( Nos1 ) and Nos2 was increased by low-intensity pulsed ultrasound (LIPUS) in MC3T3-E1 cells and primary osteoblasts. The increase of Nos1/2 expression was abrogated by both exogenous OPN overexpression and recombinant OPN treatment, whereas it was promoted by OPN-specific siRNA and OPN antibody. Moreover, LIPUS-induced phosphorylation of focal adhesion kinase (FAK), a crucial regulator of mechanoresponses, was down-regulated by OPN treatments. OPN also attenuated hepatocyte growth factor-induced vitamin D receptor ( Vdr ) expression and platelet-derived growth factor-induced cell mobility through the repression of FAK activity. Of note, the expression of low-molecular weight protein tyrosine phosphatase (LMW-PTP), a FAK phosphatase, was increased in both OPN-treated and differentiated osteoblasts. CD44 was a specific OPN receptor for LWW-PTP induction. Consistently, the suppressive influence of OPN on osteoblast responsiveness was abrogated by LMW-PTP knockdown. Taken together, these results reveal novel functions of OPN in osteoblast physiology. © 2017 Kusuyama et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Osteopontin regulates the cross-talk between phosphatidylcholine and cholesterol metabolism in mouse liver.

PubMed

Nuñez-Garcia, Maitane; Gomez-Santos, Beatriz; Buqué, Xabier; García-Rodriguez, Juan L; Romero, Marta R; Marin, Jose J G; Arteta, Beatriz; García-Monzón, Carmelo; Castaño, Luis; Syn, Wing-Kin; Fresnedo, Olatz; Aspichueta, Patricia

2017-09-01

Osteopontin (OPN) is involved in different liver pathologies in which metabolic dysregulation is a hallmark. Here, we investigated whether OPN could alter liver, and more specifically hepatocyte, lipid metabolism and the mechanism involved. In mice, lack of OPN enhanced cholesterol 7α-hydroxylase (CYP7A1) levels and promoted loss of phosphatidylcholine (PC) content in liver; in vivo treatment with recombinant (r)OPN caused opposite effects. rOPN directly decreased CYP7A1 levels through activation of focal adhesion kinase-AKT signaling in hepatocytes. PC content was also decreased in OPN-deficient (OPN-KO) hepatocytes in which de novo FA and PC synthesis was lower, whereas cholesterol (CHOL) synthesis was higher, than in WT hepatocytes. In vivo inhibition of cholesterogenesis normalized liver PC content in OPN-KO mice, demonstrating that OPN regulates the cross-talk between liver CHOL and PC metabolism. Matched liver and serum samples showed a positive correlation between serum OPN levels and liver PC and CHOL concentration in nonobese patients with nonalcoholic fatty liver. In conclusion, OPN regulates CYP7A1 levels and the metabolic fate of liver acetyl-CoA as a result of CHOL and PC metabolism interplay. The results suggest that CYP7A1 is a main axis and that serum OPN could disrupt liver PC and CHOL metabolism, contributing to nonalcoholic fatty liver disease progression in nonobese patients.

RNA Aptamer Blockade of Osteopontin Inhibits Growth and Metastasis of MDA-MB231 Breast Cancer Cells

PubMed Central

Mi, Zhiyong; Guo, Hongtao; Russell, M Benjamin; Liu, Yingmiao; Sullenger, Bruce A; Kuo, Paul C

2008-01-01

Osteopontin (OPN) is a secreted phosphoprotein which mediates tumorigenesis, local growth, and metastasis in a variety of cancers. It is a potential therapeutic target for the regulation of cancer metastasis. RNA aptamer technology targeting OPN may represent a clinically viable therapy. In this study, we characterize the critical sequence of an RNA aptamer, termed OPN-R3, directed against human OPN. It has a Kd of 18 nmol/l and binds specifically to human OPN as determined by RNA electrophoretic mobility assays. In MDA-MB231 human breast cancer cells examined under fluorescence microscopy, OPN-R3 ablates cell surface binding of OPN to its cell surface CD44 and αvβ3 integrin receptors. Critical enzymatic components of the OPN signal transduction pathways, PI3K, JNK1/2, Src and Akt, and mediators of extracellular matrix degradation, matrix metalloproteinase 2 (MMP2) and uroplasminogen activator (uPA), are significantly decreased following exposure to OPN-R3. OPN-R3 inhibits MDA-MB231 in vitro adhesion, migration, and invasion characteristics by 60, 50, and 65%, respectively. In an in vivo xenograft model of breast cancer, OPN-R3 significantly decreases local progression and distant metastases. On the basis of this “proof-of-concept” study, we conclude that RNA aptamer targeting of OPN has biologically relevance for modifying tumor growth and metastasis. PMID:18985031

The Osteopontin Level in Liver, Adipose Tissue and Serum Is Correlated with Fibrosis in Patients with Alcoholic Liver Disease

PubMed Central

Voican, Cosmin S.; Anty, Rodolphe; Saint-Paul, Marie-Christine; Rosenthal-Allieri, Maria-Alessandra; Agostini, Hélène; Njike, Micheline; Barri-Ova, Nadége; Naveau, Sylvie; Le Marchand-Brustel, Yannick; Veillon, Pascal; Calès, Paul; Perlemuter, Gabriel; Tran, Albert; Gual, Philippe

2012-01-01

Background Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis. Methodology/Principal Findings OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury. Conclusion/Significance OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease. PMID:22530059

Osteopontin Regulates Hepatitis C Virus (HCV) Replication and Assembly by Interacting with HCV Proteins and Lipid Droplets and by Binding to Receptors αVβ3 and CD44.

PubMed

Iqbal, Jawed; Sarkar-Dutta, Mehuli; McRae, Steven; Ramachandran, Akshaya; Kumar, Binod; Waris, Gulam

2018-07-01

Hepatitis C virus (HCV) replication and assembly occur at the specialized site of endoplasmic reticulum (ER) membranes and lipid droplets (LDs), respectively. Recently, several host proteins have been shown to be involved in HCV replication and assembly. In the present study, we demonstrated the important relationship among osteopontin (OPN), the ER, and LDs. OPN is a secreted phosphoprotein, and overexpression of OPN in hepatocellular carcinoma (HCC) tissue can lead to invasion and metastasis. OPN expression is also enhanced in HCV-associated HCC. Our recent studies have demonstrated the induction, proteolytic cleavage, and secretion of OPN in response to HCV infection. We also defined the critical role of secreted OPN in human hepatoma cell migration and invasion through binding to receptors integrin αVβ3 and CD44. However, the role of HCV-induced OPN in the HCV life cycle has not been elucidated. In this study, we showed a significant reduction in HCV replication, assembly, and infectivity in HCV-infected cells transfected with small interfering RNA (siRNA) against OPN, αVβ3, and CD44. We also observed the association of endogenous OPN with HCV proteins (NS3, NS5A, NS4A/B, NS5B, and core). Confocal microscopy revealed the colocalization of OPN with HCV NS5A and core in the ER and LDs, indicating a possible role for OPN in HCV replication and assembly. Interestingly, the secreted OPN activated HCV replication, infectivity, and assembly through binding to αVβ3 and CD44. Collectively, these observations provide evidence that HCV-induced OPN is critical for HCV replication and assembly. IMPORTANCE Recently, our studies uncovered the critical role of HCV-induced endogenous and secreted OPN in migration and invasion of hepatocytes. However, the role of OPN in the HCV life cycle has not been elucidated. In this study, we investigated the importance of OPN in HCV replication and assembly. We demonstrated that endogenous OPN associates with HCV NS3, NS5A, NS5B, and core proteins, which are in close proximity to the ER and LDs. Moreover, we showed that the interactions of secreted OPN with cell surface receptors αVβ3 and CD44 are critical for HCV replication and assembly. These observations provide evidence that HCV-induced endogenous and secreted OPN play pivotal roles in HCV replication and assembly in HCV-infected cells. Taken together, our findings clearly demonstrate that targeting OPN may provide opportunities for therapeutic intervention of HCV pathogenesis. Copyright © 2018 American Society for Microbiology.

Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer.

PubMed

Chang, Yoon Soo; Kim, Hyung Jung; Chang, Joon; Ahn, Chul Min; Kim, Sung Kyu; Kim, Se Kyu

2007-09-01

Osteopontin (OPN) plays important roles in tumor progression and metastasis through binding to OPN receptors such as alpha(v)beta(beta) integrin and CD44, and its overexpression in tumor is associated poor clinical outcome of NSCLC patients. Circulating OPN levels, measured by ELISA in 130 NSCLC cases that had not been treated for cancer at the time of sampling, were analyzed according to clinical, pathologic parameters and single nucleotide polymorphisms (SNPs) in the OPN gene promoter. Advanced disease states had higher circulating levels of OPN (T4 versus T1-3, N3 versus N0-2, and M1 versus M0, P=.029, .001, and .001, respectively, Kruskal-Wallis H-test), reflected by higher level of OPN in stage IV than stage I-III (P=.029, Kruskal-Wallis H-test). Among the clinical and pathological parameters including age, gender, smoking status, histologic subtypes and grade of differentiation, smoking status influences circulating OPN level showing higher level of OPN in ex-smokers than current and non-smokers (P=.038, Kruskal-Wallis H-test). Variation at nucleotide (nt) -443 of the OPN gene promoter had no influence on circulating OPN levels, however, patients with G/G at nt -156 showed higher concentrations of OPN than those with G/GG or GG/GG (P=.003, Kruskal-Wallis H-test). A patient with G/G at nt -156 was more frequently diagnosed with advanced stage (IIIB-IV) than with early stage (I-IIIA) NSCLC (P=.048, Mantel-Haenszel-test). In multivariate analysis, stage is the only independent factor influencing circulating level of OPN. Although circulating level of OPN in the patients with bone metastasis was higher than in those without bone metastasis (P=.028, Mann-Whitney U-test), there was no difference in the OPN levels between bone metastasis group and non-bone metastasis group. Given that the elevated levels of OPN is associated with advanced stages of NSCLC, elucidating OPN regulatory mechanisms may contribute to the development of a new therapeutic modality for NSCLC.

Robotic assisted laparoscopic partial nephrectomy using contrast-enhanced ultrasound scan to map renal blood flow.

PubMed

Alenezi, Ahmad; Motiwala, Aamir; Eves, Susannah; Gray, Rob; Thomas, Asha; Meiers, Isabelle; Sharif, Haytham; Motiwala, Hanif; Laniado, Marc; Karim, Omer

2017-03-01

The paper describes novel real-time 'in situ mapping' and 'sequential occlusion angiography' to facilitate selective ischaemia robotic partial nephrectomy (RPN) using intraoperative contrast enhanced ultrasound scan (CEUS). Data were collected and assessed for 60 patients (61 tumours) between 2009 and 2013. 31 (50.8%) tumours underwent 'Global Ischaemia', 27 (44.3%) underwent 'Selective Ischaemia' and 3 (4.9%) were removed 'Off Clamp Zero Ischaemia'. Demographics, operative variables, complications, renal pathology and outcomes were assessed. Median PADUA score was 9 (range 7-10). The mean warm ischaemia time in selective ischaemia was less and statistically significant than in global ischaemia (17.1 and 21.4, respectively). Mean operative time was 163 min. Postoperative complications (n = 10) included three (5%) Clavien grade 3 or above. Malignancy was demonstrated in 47 (77%) with negative margin in 43 (91.5%) and positive margin in four (8.5%). Long-term decrease in eGFR post selective ischaemia robotic partial nephrectomy was less compared with global ischaemia (four and eight, respectively) but not statistically significant. This technique is safe, feasible and cost-effective with comparable perioperative outcomes. The technical aspects elucidate the role of intraoperative CEUS to facilitate and ascertain selective ischaemia. Further work is required to demonstrate long-term oncological outcomes. © 2016 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons, Ltd. © 2016 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons, Ltd.

Hilar Parenchymal Oversew: a novel technique for robotic partial nephrectomy hilar tumor renorrhaphy.

PubMed

Chavali, Jaya Sai S; Nelson, Ryan; Maurice, Matthew J; Kara, Onder; Mouracade, Pascal; Dagenais, Julien; Reese, Jeremy; Bayona, Pilar; Haber, Georges-Pascal; Stein, Robert J

2018-01-01

A renorrhaphy technique which is effective for hemostasis but does not place undue tension on the branch vessels of the renal sinus remains one of the challenging steps after hilar tumor resection during robotic partial nephrectomy (RPN). The published V-hilar suture (VHS) technique is one option for reconstruction after an RPN involving the hilum. The objective of this video is to show a novel renorrhaphy technique, Hilar Parenchymal Oversew that has been effective for such cases. We present two cases of RPN for renal hilar tumors. The first case depicts use of the VHS renorrhaphy technique for a tumor that abuts the renal hilum along 20% of its diameter. The second case demonstrates tumor resection and reconstruction for a tumor that has >50% involvement of the hilum along its diameter. After tumor resection, individual sinus vessels can be selectively oversewn with 2-0 Vicryl suture on SH needle. The remaining exposed parenchyma is controlled using the Hilar Parenchymal Oversew technique with a #0 Vicryl on CT-1 needle. For the Hilar Parenchymal Oversew surgery operative time was 225 min, estimated blood loss was 140 ml, warm ischemia time was 19 minutes, and there were no intraoperative complications. Pathology was consistent with clear cell renal cancer with negative margins. Robotic partial nephrectomy with the Hilar Parenchymal Oversew technique is a good alternative to VHS renorrhaphy in the management of renal hilar tumors "bulging" into the renal sinus with >50% of the tumor diameter abutting the hilum. Copyright® by the International Brazilian Journal of Urology.

Hybrid laparoscopic and robotic ultrasound-guided radiofrequency ablation-assisted clampless partial nephrectomy.

PubMed

Nadler, Robert B; Perry, Kent T; Smith, Norm D

2009-07-01

To describe a clampless approach made possible by creating an avascular plane of tissue with radiofrequency ablation. Laparoscopic partial nephrectomy is slowly gaining acceptance as a method to treat small (<4 cm) and select moderate (<7 cm) renal masses. The intricacies of laparoscopic suturing, which result in prolonged warm ischemia times, have delayed the widespread acceptance of this technique among urologists. Laparoscopic suturing to close the collecting system was done using the da Vinci robot. An avascular plane of tissue from coagulation necrosis was achieved with the Habib 4X radiofrequency ablation device and the Rita 1500X generator. Typically, we used a power setting of 50 W but have found settings as low as 25 W necessary to provide hemostasis for larger vessels. The tumor was then sharply excised with a negative margin using robotic scissors and electrocautery to facilitate tissue cutting. Retrograde injection of methylthioninium chloride and saline through an externalized ureteral catheter allowed for precise sutured closure of the collecting system. FloSeal and BioGlue were then applied, making surgical bolsters or parenchymal sutures unnecessary. Intraoperative histologic evaluation of the surgical margin and repeat resection of the tumor bed was possible because the renal hilum was not clamped, and no warm ischemia was used. This technique, which combines the improving technologies of robotic surgery, intraoperative laparoscopic ultrasonography, and radiofrequency ablation, might make more surgeons comfortable with the intricacies of laparoscopic suturing and eliminate prolonged warm ischemia times. Overall, this method should result in more patients being able to undergo minimally invasive laparoscopic partial nephrectomy.

Integrating robotic partial nephrectomy to an existing robotic surgery program.

PubMed

Yuh, Bertram; Muldrew, Shantel; Menchaca, Anita; Yip, Wesley; Lau, Clayton; Wilson, Timothy; Josephson, David

2012-04-01

As more centers develop robotic proficiency, progressing to a successful robot-assisted partial nephrectomy (RAPN) program depends on a number of factors. We describe our technique, results, and analysis of program setup for RAPN. Between 2005 and 2011, 92 RAPNs were performed following maturation of a robotic prostatectomy program. Operating rooms and supply rooms were outfitted for efficient robotic throughput. Tilepro and intraoperative ultrasound were used for all cases. Training and experiential learning for surgeons, anesthesia and nursing staff was a high priority. An onsite robotic technician helped troubleshoot, prepare the room and staff prior to starting surgery, and provide assistance with different robotic models. Average operative time decreased over time from 235 min to 199 min (p = .03). Warm ischemia time decreased from 26 minutes to 23 minutes (p = .02) despite an increased complexity of tumors and operations on multiple tumors. Median estimated blood loss was 150 mL. Average length of hospital stay was 3 days (range 1-9). Average size of lesions was 2.7 cm (range 0.7-8.6). Final pathology demonstrated 71 (77%) malignant lesions and 21 (23%) benign lesions. The addition of a robot-assisted partial nephrectomy program to an institutional robotic program can be coordinated with several key steps. Outcomes from an operational, oncologic, and renal functional standpoint are acceptable. Despite increased complexity of tumors and treatment of multiple lesions, operative and warm ischemia times showed a decrease over time. An organizational model that involves the surgeons, anesthesia, nursing staff, and possibly a robotic technical specialist helps to overcome the learning curve.

Osteopontin Signals through Calcium and Nuclear Factor of Activated T Cells (NFAT) in Osteoclasts

PubMed Central

Tanabe, Natsuko; Wheal, Benjamin D.; Kwon, Jiyun; Chen, Hong H.; Shugg, Ryan P. P.; Sims, Stephen M.; Goldberg, Harvey A.; Dixon, S. Jeffrey

2011-01-01

Osteopontin (OPN), an integrin-binding extracellular matrix glycoprotein, enhances osteoclast activity; however, its mechanisms of action are elusive. The Ca2+-dependent transcription factor NFATc1 is essential for osteoclast differentiation. We assessed the effects of OPN on NFATc1, which translocates to nuclei upon activation. Osteoclasts from neonatal rabbits and rats were plated on coverslips, uncoated or coated with OPN or bovine albumin. OPN enhanced the proportion of osteoclasts exhibiting nuclear NFATc1. An RGD-containing, integrin-blocking peptide prevented the translocation of NFATc1 induced by OPN. Moreover, mutant OPN lacking RGD failed to induce translocation of NFATc1. Thus, activation of NFATc1 is dependent on integrin binding through RGD. Using fluorescence imaging, OPN was found to increase the proportion of osteoclasts exhibiting transient elevations in cytosolic Ca2+ (oscillations). OPN also enhanced osteoclast survival. The intracellular Ca2+ chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) suppressed Ca2+ oscillations and inhibited increases in NFATc1 translocation and survival induced by OPN. Furthermore, a specific, cell-permeable peptide inhibitor of NFAT activation blocked the effects of OPN on NFATc1 translocation and osteoclast survival. This is the first demonstration that OPN activates NFATc1 and enhances osteoclast survival through a Ca2+-NFAT-dependent pathway. Increased NFATc1 activity and enhanced osteoclast survival may account for the stimulatory effects of OPN on osteoclast function in vivo. PMID:21940634

Evaluating the efficacy of osteopontin expression as a prognostic marker in oral squamous cell carcinoma in the Indian subpopulation.

PubMed

Ingale, Yashwant; Routray, Samapika; Kheur, Supriya M; Kheur, Mohit; Mohanty, Neeta

2014-09-01

This study aimed to correlate the prognostic value of osteopontin (OPN) expression using both tissue and plasma samples from patients with clinically and histologically confirmed oral squamous cell carcinoma (OSCC). The study group comprised of sixty patients (n = 60), which were clinically and histologically diagnosed for oral squamous cell carcinoma (OSCC). The Control group comprised of ten (n = 10) healthy volunteers. Plasma OPN levels were assayed using a quantitative enzyme-linked immunosorbent assay (OPN ELISA). Expression of OPN was also identified and evaluated by immunohistochemistry in tissue sections. These OPN expressions were then correlated with different parameters like age, sex, site, clinical presentation, tumor node metastasis (TNM) staging, histopathological grading and lymph node metastasis. One-way analysis of variance (ANOVA) was used to evaluate the difference in tissue intensity and plasma OPN levels between the OSCC and the normal control groups. The distribution of the plasma OPN levels and tissue OPN intensity in OSCC cohorts were compared to histopathological grades and analyzed. When evaluated OPN expression in tissue had higher intensity observed in OSCC (95% +ve) cases. And the mean plasma OPN concentration in OSCC cohort was more in comparison to the normal cohort. The results clearly showed that the plasma OPN levels and intensity grading in tissue correlated with tumor grades. The study highlights OPN as a biomarker for prognosis in OSCC in both plasma and tissue samples. We would like to emphasize on the evaluation of plasma OPN as a protocol of blood examination for all cancer patient, as it may serve as an indicator for tumor progression and potential risk of metastasis.

Bone toughness at the molecular scale: A model for fracture toughness using crosslinked osteopontin on synthetic and biogenic mineral substrates.

PubMed

Cavelier, S; Dastjerdi, A K; McKee, M D; Barthelat, F

2018-05-01

The most prominent structural components in bone are collagen and mineral. However, bone additionally contains a substantial amount of noncollagenous proteins (most notably of the SIBLING protein family), some of which may act as cohesive/adhesive "binders" for the composite hybrid collagen/mineral scaffolding, whether in the bulk phase of bone, or at its interfaces. One such noncollagenous protein - osteopontin (OPN) - appears to be critical to the deformability and fracture toughness of bone. In the present study, we used a reconstructed synthetic mineral-OPN-mineral interface, and a biogenic (natural tooth dentin) mineral/collagen-OPN-mineral/collagen interface, to measure the fracture toughness of OPN on mineralized substrates. We used this system to test the hypothesis that OPN crosslinking by the enzyme tissue transglutaminase 2 (TG2) that is found in bone enhances interfacial adhesion to increase the fracture toughness of bone. For this, we prepared double-cantilever beam substrates of synthetic pure hydroxyapatite mineral, and of narwhal dentin, and directly apposed them to one another under different intervening OPN/crosslinking conditions, and fracture toughness was tested using a miniaturized loading stage. The work-of-fracture of the OPN interface was measured for different OPN formulations (monomer vs. polymer), crosslinking states, and substrate composition. Noncrosslinked OPN provided negligible adhesion on pure hydroxyapatite, whereas OPN crosslinking (by the chemical crosslinker glutaraldehyde, and TG2 enzyme) provided strong interfacial adhesion for both hydroxyapatite and dentin using monomeric and polymeric OPN. Pre-coating of the substrate beams with monomeric OPN further improved the adhesive performance of the samples, likely by allowing effective binding of this nascent OPN form to mineral/matrix components, with this pre-attachment providing a protein layer for additional crosslinking between the substrates. Copyright © 2018 Elsevier Inc. All rights reserved.

Identification of Transglutaminase Reactive Residues in Human Osteopontin and Their Role in Polymerization

PubMed Central

Christensen, Brian; Zachariae, Elias D.; Scavenius, Carsten; Thybo, Morten; Callesen, Morten M.; Kløverpris, Søren; Oxvig, Claus; Enghild, Jan J.; Sørensen, Esben S.

2014-01-01

Osteopontin (OPN) is a highly posttranslationally modified protein present in several tissues where it is implicated in numerous physiological processes. OPN primarily exerts its functions through interaction with integrins via the Arg-Gly-Asp and Ser-Val-Val-Tyr-Gly-Leu-Arg sequences located in the N-terminal part of the protein. OPN can be polymerized by the cross-linking enzyme transglutaminase 2 (TG2), and polymerization has been shown to enhance the biological activity of OPN. However, little is known about the reactivity and location of the glutamine and lysine residues involved in the TG2-mediated modification of OPN. Here we show that TG2 catalyses the incorporation of 5-(Biotinamido)pentylamine at glutamines in both the N- and C-terminal parts of OPN, whereas TG2 primarily incorporated the glutamine-donor peptide biotinyl-TVQQEL-OH into the C-terminal part of OPN. By mass spectrometric analyses we identified Gln34, Gln42, Gln193 and Gln248 as the major TG2 reactive glutamines in OPN. The distribution of reactive Gln and Lys residues in OPN proved to be important, as the full-length protein but not the physiologically highly active integrin-binding N-terminal part of OPN were able to polymerize in a TG2-mediated reaction. Collectively, these data provide important new molecular knowledge about the mechanism of OPN polymerization. PMID:25419572

Is Osteopontin a Friend or Foe of Cell Apoptosis in Inflammatory Gastrointestinal and Liver Diseases?

PubMed

Iida, Tomoya; Wagatsuma, Kohei; Hirayama, Daisuke; Nakase, Hiroshi

2017-12-21

Osteopontin (OPN) is involved in a variety of biological processes, including bone remodeling, innate immunity, acute and chronic inflammation, and cancer. The expression of OPN occurs in various tissues and cells, including intestinal epithelial cells and immune cells such as macrophages, dendritic cells, and T lymphocytes. OPN plays an important role in the efficient development of T helper 1 immune responses and cell survival by inhibiting apoptosis. The association of OPN with apoptosis has been investigated. In this review, we described the role of OPN in inflammatory gastrointestinal and liver diseases, focusing on the association of OPN with apoptosis. OPN changes its association with apoptosis depending on the type of disease and the phase of disease activity, acting as a promoter or a suppressor of inflammation and inflammatory carcinogenesis. It is essential that the roles of OPN in those diseases are elucidated, and treatments based on its mechanism are developed.

American Confederation of Urology (CAU) experience in minimally invasive partial nephrectomy.

PubMed

Secin, Fernando P; Castillo, Octavio A; Rozanec, José J; Featherston, Marcelo; Holst, Pablo; Milfont, José Cocisfran Alves; García Marchiñena, Patricio; Jurado Navarro, Alberto; Autrán, Anamaría; Rovegno, Agustín R; Faba, Oscar Rodríguez; Palou, Joan; Teixeira Dubeux, Victor; Nuñez Bragayrac, Luciano; Sotelo, Rene; Zequi, Stenio; Guimarães, Gustavo Cardoso; Álvarez-Maestro, Mario; Martínez-Piñeiro, Luis; Villoldo, Gustavo; Villaronga, Alberto; Abreu Clavijo, Diego; Decia, Ricardo; Frota, Rodrigo; Vidal-Mora, Ivar; Finkelstein, Diana; Monzó Gardiner, Juan I; Schatloff, Oscar; Hernández-Porrás, Andres; Santaella-Torres, Félix; Quesada, Emilio T; Sánchez-Salas, Rodolfo; Dávila, Hugo; Mavric, Humberto Villavicencio

2017-01-01

To describe the perioperative and oncology outcomes in a series of laparoscopic or robotic partial nephrectomies (PN) for renal tumors treated in diverse institutions of Hispanic America from the beginning of their minimally invasive (MI) PN experience through December 2014. Seventeen institutions participated in the CAU generated a MI PN database. We estimated proportions, medians, 95 % confidence intervals, Kaplan-Meier curves, multivariate logistic and Cox regression analyses. Clavien-Dindo classification was used. We evaluated 1501 laparoscopic (98 %) or robotic (2 %) PNs. Median age: 58 years. Median surgical time, warm ischemia and intraoperative bleeding were 150, 20 min and 200 cc. 81 % of the lesions were malignant, with clear cell histology being 65 % of the total. Median maximum tumor diameter is 2.7 cm, positive margin is 8.2 %, and median hospitalization is 3 days. One or more postoperative complication was recorded in 19.8 % of the patients: Clavien 1: 5.6 %; Clavien 2: 8.4 %; Clavien 3A: 1.5 %; Clavien 3B: 3.2 %; Clavien 4A: 1 %; Clavien 4B: 0.1 %; Clavien 5: 0 %. Bleeding was the main cause of a reoperation (5.5 %), conversion to radical nephrectomy (3 %) or open partial nephrectomy (6 %). Transfusion rate is 10 %. In multivariate analysis, RENAL nephrometry score was the only variable associated with complications (OR 1.1; 95 % CI 1.02-1.2; p = 0.02). Nineteen patients presented disease progression or died of disease in a median follow-up of 1.37 years. The 5-year progression or kidney cancer mortality-free rate was 94 % (95 % CI 90, 97). Positive margins (HR 4.98; 95 % CI 1.3-19; p = 0.02) and females (HR 5.6; 95 % CI 1.7-19; p = 0.005) were associated with disease progression or kidney cancer mortality after adjusting for maximum tumor diameter. Laparoscopic PN in these centers of Hispanic America seem to have acceptable perioperative complications and short-term oncologic outcomes.

Osteopontin in Systemic Sclerosis and its Role in Dermal Fibrosis

PubMed Central

Wu, Minghua; Schneider, Daniel J.; Mayes, Maureen D; Assassi, Shervin; Arnett, Frank C.; Tan, Filemon K.; Blackburn, Michael R.; Agarwal, Sandeep K.

2012-01-01

Osteopontin (OPN) is a matricellular protein with proinflammatory and profibrotic properties. Previous reports demonstrate a role for OPN in wound healing and pulmonary fibrosis. Herein, we determined if OPN levels are increased in a large cohort of systemic sclerosis (SSc) patients and if OPN contributes dermal fibrosis. Plasma OPN levels were increased in SSc patients, including patients with limited and diffuse disease, compared to healthy controls. Immunohistology demonstrated OPN on fibroblast-like and inflammatory cells in SSc skin and lesional skin from mice in the bleomycin-induced dermal fibrosis model. OPN deficient (OPN−/−) mice developed less dermal fibrosis compared to wild-type mice in the bleomycin-induced dermal fibrosis model. Additional in vivo studies demonstrated that lesional skin from OPN−/− mice had fewer Mac-3+ cells, fewer myofibroblasts, decreased TGF-beta (TGFβ) and genes in the TGFβ pathway and decreased numbers of cells expressing phosphorylated SMAD2 (pSMAD) and ERK. In vitro, OPN−/− dermal fibroblasts had decreased migratory capacity but similar phosphorylation of SMAD2 by TGFβ. Finally, TGFβ production by OPN deficient macrophages was reduced compared to wild type. These data demonstrate an important role for OPN in the development of dermal fibrosis and suggest that OPN may be a novel therapeutic target in SSc. PMID:22402440

Cleaved Form of Osteopontin in Urine as a Clinical Marker of Lupus Nephritis

PubMed Central

Kitagori, Koji; Yoshifuji, Hajime; Oku, Takuma; Sasaki, Chiyomi; Miyata, Hitomi; Mori, Keita P.; Nakajima, Toshiki; Ohmura, Koichiro; Kawabata, Daisuke; Yukawa, Naoichiro; Imura, Yoshitaka; Murakami, Kosaku; Nakashima, Ran; Usui, Takashi; Fujii, Takao; Sakai, Kaoru; Yanagita, Motoko; Hirayama, Yoshitaka; Mimori, Tsuneyo

2016-01-01

We assessed the utility of two forms of osteopontin (OPN), OPN full and its cleaved form (OPN N-half), in plasma and urine as markers of disease activity in lupus nephritis (LN). Samples were collected from patients with systemic lupus erythematosus (SLE) (LN: N = 29, non-LN: N = 27), IgA nephropathy (IgAN) (N = 14), minimal change nephrotic syndrome (MCNS) (N = 5), diabetic nephropathy (DN) (N = 14) and healthy volunteers (HC) (N = 17). While there was no significant difference in urine OPN full concentration between groups, urine OPN N-half concentration was significantly higher in patients with LN than HC (p < 0.05). Moreover, urine OPN N-half was higher in LN patients with overt proteinuria (urine protein/creatinine ratio: P/C > 0.5) than LN patients with minimal proteinuria (P/C < 0.5, p < 0.0001), and also higher than in DN patients with overt proteinuria (P/C > 0.5, p < 0.01). Urine thrombin activity correlated with urine OPN N-half concentration (p < 0.0001), but not with urine OPN full concentration. These results suggest that urine OPN N-half concentration reflects renal inflammation. Thus, urine OPN N-half may be a novel disease activity marker for LN. PMID:27992535

Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy.

PubMed

Goel, Utsav O; Maddox, Michael M; Elfer, Katherine N; Dorsey, Philip J; Wang, Mei; McCaslin, Ian Ross; Brown, J Quincy; Lee, Benjamin R

2014-01-01

Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals ). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy

NASA Astrophysics Data System (ADS)

Goel, Utsav O.; Maddox, Michael M.; Elfer, Katherine N.; Dorsey, Philip J.; Wang, Mei; McCaslin, Ian Ross; Brown, J. Quincy; Lee, Benjamin R.

2014-10-01

Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

Inhibition of osteopontin suppresses in vitro and in vivo angiogenesis in endometrial cancer.

PubMed

Du, Xue-lian; Jiang, Tao; Sheng, Xiu-gui; Gao, Rong; Li, Qing-shui

2009-12-01

Osteopontin (OPN) has been found to play an important role in tumor angiogenesis in recent years. Our previous studies have shown that OPN is overexpressed in tumor-associated human endometrial endothelial cells (HEECs) isolated from tissue samples of patients with endometrial cancer. In the present study, we aimed to further determine the role of OPN in endometrial cancer-associated angiogenesis. We knock down OPN expression in HEECs and human endometrial cancer Ishikawa (ISK) cells using the small interference RNA method, and then evaluate the effects of OPN on endometrial cancer-associated angiogenesis by in vivo mouse studies and in vitro assays. Our results revealed that proliferative activity of HEECs and ISK cells in vitro was not affected by transfection with the siOPN-RNA (P>0.05). Inhibition of OPN expression in HEECs reduced the cell migration, with the percentage of repaired area of 36.32+/-2.88 vs. 8.54+/-1.13 (P=0.007). HEEC/siOPN and ISK/siOPN demonstrated 67.4% and 51.2% decreased invasiveness compared with controls, respectively (P<0.05). The number of branched points per well was obviously lower in HEEC/siOPN than that in HEEC/Control (32.46+/-17.10 vs. 53.15+/-15.44, P=0.021). Furthermore, ISK cells transfected with OPN siRNA formed smaller tumor in mice and led to a lower microvessel density, i.e., angiogenesis, in transplanted tumors of mice than scrambled siRNA controls (12.88+/-7.14 vs. 28.42+/-9.69 vessels per HPF, P=0.019). These data confirm the positive role of OPN in endometrial cancer-associated angiogenesis and might be of great benefit for finding rational approach in endometrial cancer therapy.

Nephron sparing by partial median nephrectomy for treatment of renal hemangioma in a dog.

PubMed

Mott, J C; McAnulty, J F; Darien, D L; Steinberg, H

1996-04-15

A 6-year-old neutered male Golden Retriever was admitted for evaluation of intermittent hematuria of 2 months' duration. A 3-cm heterogeneous mass causing distortion of the caudomedial aspect of the left kidney was detected via ultrasonography. Histologic examination of a renal tissue sample obtained by ultrasound-guided biopsy revealed a telangiectatic vascular plexus of unknown origin. Low glomerular filtration rate was identified by a modified exogenous creatinine clearance test. Excretory urography revealed a filling defect in the medial aspect of the caudal pole of the kidney, near the hilus. Because total renal function was low, a decision was made to perform nephron-sparing surgery involving resection of centrally located renal parenchymal and pelvic tissue by en bloc resection in the median plane, instead of radical nephrectomy. After surgery, the hematuria resolved and further decrease in renal function was not evident. Nephron-sparing surgery is a viable option for dogs with compromised renal function when there is concern that radical nephrectomy may precipitate uremia.

Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

PubMed

Pereira, Thiago A; Syn, Wing-Kin; Machado, Mariana V; Vidigal, Paula V; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M; Santos, Elisângela T; Chan, Isaac S; Trindade, Guilherme V M; Choi, Steve S; Witek, Rafal P; Pereira, Fausto E; Secor, William E; Andrade, Zilton A; Lambertucci, José Roberto; Diehl, Anna Mae

2015-11-01

Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity. © 2015 Authors; published by Portland Press Limited.

Benign lesions after partial nephrectomy for presumed renal cell carcinoma in masses 4 cm or less: prevalence and predictors in Korean patients.

PubMed

Jeon, Hwang Gyun; Lee, Seung Ryeol; Kim, Kwang Hyun; Oh, Young Taik; Cho, Nam Hoon; Rha, Koon Ho; Yang, Seung Choul; Han, Woong Kyu

2010-09-01

To investigate the prevalence and predictors associated with benign lesions in Korean patients after partial nephrectomy for presumed renal cell carcinoma (RCC) for lesions measuring ≤ 4 cm. We retrospectively investigated the medical records of 376 patients who underwent partial nephrectomy for presumed RCC with renal masses of size ≤ 4 cm between June 1997 and December 2008. Demographic and clinicopathologic parameters were compared between benign lesions and RCC. Logistic regression was done to identify parameters associated with benign lesions. In the 376 patients, 81 tumors (21.5%) were benign, including 35 angiomyolipomas (9.3%), 26 complicated cysts (6.9%), 11 oncocytomas (2.9%), and 9 others (2.4%). Univariate analysis showed that time of surgery, female sex, younger age, and normal body mass index (body mass index (BMI) < 23 kg/m(2)) were associated with benign pathologic findings. On multiple logistic regression analysis, female sex (OR, 4.91; 95% CI, 2.76-08.75; P < .001), age (OR, 0.97; 95% CI, 0.95-0.99; P = .009), and time of surgery (OR, 0.33; 95% CI, 0.11-0.95; P = .040) were independent predictors of benign histologic features. Tumor size, incidental diagnosis, and BMI were not significant predictors (P > .05). Our study with a large cohort of Asian patients showed that the prevalence of benign lesions was similar to previously reported Western studies. However, the most common benign lesion was angiomyolipoma, compared with oncocytoma in Western countries. The results of this study may help clinicians counsel female and younger patients recently diagnosed with small renal masses and decide the most appropriate treatment, including renal biopsies and close observation. Copyright © 2010 Elsevier Inc. All rights reserved.

Anatomic comparison of traditional and enucleation partial nephrectomy specimens.

PubMed

Calaway, Adam C; Gondim, Dibson D; Flack, Chandra K; Jacob, Joseph M; Idrees, Muhammad T; Boris, Ronald S

2017-05-01

To compare pseudocapsule (PC) properties of clear cell renal cell carcinoma tumors removed via both traditional partial nephrectomy (PNx) and enucleative techniques as well as quantify the difference in volume of normal renal parenchyma removed between groups. A retrospective review of clear cell PNx specimens between 2011 and 2014 was performed. All patients undergoing tumor enucleation (TE) were included. A single pathologist reviewed the pathological specimens. This cohort was compared with a previously collected clear cell traditional PNx database. A total of 47 clear cell partial nephrectomies were reviewed (34 PNx and 13 TE). Invasion of tumor completely through the PC and positive surgical margins were seen in 2 (5.8%) and 1 (7.7%) of traditional and TE specimens, respectively (P = 0.82). PC mean (0.63 vs. 0.52mm), maximum (1.39 vs. 1.65mm), and minimum thickness (0.27 vs. 0.19mm) were similar between cohorts (P = 0.29, P = 0.36, and P = 0.44). Gross specimen volume varied considerably between the 2 groups (35.6 vs. 17.9cm 3 , P≤0.05) although tumor volume did not (12 vs. 14.2cm 3 , P = 0.64). The renal tumor consisted of only 37% of the total volume of the traditional PNx specimens compared to 80% of the volume in TEs (P<0.01). Four TE specimens (31%) were "true" TEs (no additional parenchyma identified outside of the PC). PC properties appear independent of surgical technique. True TEs are uncommon. Regardless, there is considerable volume discrepancy of normal renal parenchymal removed between enucleative and nonenucleative PNx groups. Copyright © 2017 Elsevier Inc. All rights reserved.

Early impact of robot-assisted partial nephrectomy on renal function as assessed by renal scintigraphy.

PubMed

Luciani, Lorenzo G; Chiodini, Stefano; Donner, Davide; Cai, Tommaso; Vattovani, Valentino; Tiscione, Daniele; Giusti, Guido; Proietti, Silvia; Chierichetti, Franca; Malossini, Gianni

2016-06-01

To measure the early impact of robot-assisted partial nephrectomy (RAPN) on renal function as assessed by renal scan (Tc 99m-DTPA), addressing the issue of risk factors for ischemic damage to the kidney. All patients undergoing RAPN for cT1 renal masses between June 2013 and May 2014 were included in this prospective study. Renal function as expressed by glomerular filtration rate (GFR) was assessed by Technetium 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scan preoperatively and postoperatively at 1 month in every patient. A multivariable analysis was used for the determination of independent factors predictive of GFR decrease of the operated kidney. Overall, 32 patients underwent RAPN in the time interval. Median tumor size, blood loss, and ischemia time were 4 cm, 200 mL, and 24 min, respectively. Two grade III complications occurred (postoperative bleeding in the renal fossa, urinoma). The GFR of the operated kidney decreased significantly from 51.7 ± 15.1 mL/min per 1.73 m(2) preoperatively to 40, 12 ± 12.4 mL/min per 1.73 m(2) 1 month postoperatively (p = 0.001) with a decrease of 22.4 %. On multivariable analysis, only tumor size (p = 0.05) was a predictor of GFR decrease of the operated kidney. Robotic-assisted partial nephrectomy had a detectable impact on early renal function in a series of relatively large tumors and prevailing intermediate nephrometric risk. A mean decrease of 22 % of GFR as assessed by renal scan in the operated kidney was found at 1 month postoperatively. In multivariable analysis, tumor size only was a significant predictor of renal function loss.

3D-printed soft-tissue physical models of renal malignancies for individualized surgical simulation: a feasibility study.

PubMed

Maddox, Michael M; Feibus, Allison; Liu, James; Wang, Julie; Thomas, Raju; Silberstein, Jonathan L

2018-03-01

To construct patient-specific physical three-dimensional (3D) models of renal units with materials that approximates the properties of renal tissue to allow pre-operative and robotic training surgical simulation, 3D physical kidney models were created (3DSystems, Rock Hill, SC) using computerized tomography to segment structures of interest (parenchyma, vasculature, collection system, and tumor). Images were converted to a 3D surface mesh file for fabrication using a multi-jet 3D printer. A novel construction technique was employed to approximate normal renal tissue texture, printers selectively deposited photopolymer material forming the outer shell of the kidney, and subsequently, an agarose gel solution was injected into the inner cavity recreating the spongier renal parenchyma. We constructed seven models of renal units with suspected malignancies. Partial nephrectomy and renorrhaphy were performed on each of the replicas. Subsequently all patients successfully underwent robotic partial nephrectomy. Average tumor diameter was 4.4 cm, warm ischemia time was 25 min, RENAL nephrometry score was 7.4, and surgical margins were negative. A comparison was made between the seven cases and the Tulane Urology prospectively maintained robotic partial nephrectomy database. Patients with surgical models had larger tumors, higher nephrometry score, longer warm ischemic time, fewer positive surgical margins, shorter hospitalization, and fewer post-operative complications; however, the only significant finding was lower estimated blood loss (186 cc vs 236; p = 0.01). In this feasibility study, pre-operative resectable physical 3D models can be constructed and used as patient-specific surgical simulation tools; further study will need to demonstrate if this results in improvement of surgical outcomes and robotic simulation education.

A New Sliding-Loop Technique in Renorrhaphy for Partial Nephrectomy: A Feasibility Study in a Porcine Model.

PubMed

Lee, Jung Keun; Oh, Jong Jin; Lee, Sangchul; Lee, Seung Bae; Byun, Seok-Soo; Lee, Sang Eun; Jeong, Chang Wook

2016-04-01

We developed a sliding-loop technique that narrowed both sides of the parenchyma in a porcine model and compared it with the conventional sliding-clip technique. Three pigs (30-40 kg) were reused following another experiment conducted by the same researchers. Bilateral kidneys were harvested within 30 minutes after euthanasia. Two partial nephrectomies per kidney were performed on opposite surfaces. All kidney defects were of the same size (diameter of 2.5-3 cm with a depth of 1.0-1.5 cm). The sliding-clip technique and sliding-loop technique were performed separately. In the sliding-loop technique, we created a 1-cm loop at the end of a Vicryl and placed a tetrafluoroethylene polymer pledget in front of the knots passing through the needle. The needle then crossed the loop after passing through the renal parenchyma. A Weck clip was placed and slid on one side to tighten the suture. Tightening was controlled with an equivalent force using a digital push-pull gauge. Three stitches were placed at each renorrhaphy site. The distance between repaired renal surfaces was measured at 5 different points (3 suture sites and 2 middle sites between sutures). The results of the 2 techniques were compared by using the independent t test. The mean distance between renal surfaces was significantly narrower in the sliding-loop technique than in the conventional technique (1.80 ± 1.08 mm vs 5.28 ± 2.46 mm, P < .001). In the porcine model, the sliding-loop technique more effectively closed the partial nephrectomy defects compared with the conventional sliding-clip technique. © The Author(s) 2015.

Osteopontin is a tumor autoantigen in prostate cancer patients

PubMed Central

TILLI, TATIANA M.; SILVA, ELOÍSIO A.; MATOS, LÍVIA C.; FAGET, DOUGLAS V.; DIAS, BIANCA F.P.; VASCONCELOS, JULIANA S.P.; YOKOSAKI, YASUYUKI; GIMBA, ETEL R.P.

2011-01-01

Anti-tumor antibodies act as biomarkers for the early diagnosis of prostate cancer (PCa). Osteopontin (OPN) is overexpressed in PCa cells and contributes to the progression of the disease. This study aimed to evaluate whether OPN evokes a humoral immune response in PCa patients and whether the reactivity levels of anti-OPN antibodies may be used to better differentiate PCa from benign and healthy donor plasma samples. Plasma samples from biopsy-proven PCa patients (29), benign prostate hyperplasia (BPH) (18) and control healthy donors (HD) (30) were tested by immunoblots using the recombinant human OPN. The frequency of anti-OPN antibodies was significantly higher in PCa (66%) plasma samples as compared to BPH (33%) and HD controls (10%). Anti-OPN antibodies were detected in a high proportion of plasma samples from patients with a Gleason score of less than 6 (57%), prostate-specific antigen levels lower than 10 ng/ml (67%) and pT2 organ-confined disease (70%), suggesting that anti-OPN antibodies may be used as an early serum marker for PCa. To the best of our knowledge, this is the first description of OPN as a tumor autoantigen and one of the most reactive individual autoantigens described thus far. These data support the inclusion of OPN in a multiplex of tumor antigens in order to perform antibody profiling in PCa as well as in other malignancies overexpressing OPN. PMID:22870138

Progressive Secondary Neurodegeneration and Microcalcification Co-Occur in Osteopontin-Deficient Mice

PubMed Central

Maetzler, Walter; Berg, Daniela; Funke, Claudia; Sandmann, Freya; Stünitz, Holger; Maetzler, Corina; Nitsch, Cordula

2010-01-01

In the brain, osteopontin (OPN) may function in a variety of pathological conditions, including neurodegeneration, microcalcification, and inflammation. In this study, we addressed the role of OPN in primary and secondary neurodegeneration, microcalcification, and inflammation after an excitotoxic lesion by examining OPN knock-out (KO) mice. Two, four, and ten weeks after injection of the glutamate analogue ibotenate into the corticostriatal boundary, the brains of 12 mice per survival time and strain were evaluated. OPN was detectable in neuron-shaped cells, in microglia, and at the surface of dense calcium deposits. At this primary lesion site, although the glial reaction was attenuated in OPN-KO mice, lesion size and presence of microcalcification were comparable between OPN-KO and wild-type mice. In contrast, secondary neurodegeneration at the thalamus was more prominent in OPN-KO mice, and this difference increased over time. This was paralleled by a dramatic rise in the regional extent of dense microcalcification. Despite these differences, the numbers of glial cells did not significantly differ between the two strains. This study demonstrates for the first time a genetic model with co-occurrence of neurodegeneration and microcalcification, mediated by the lack of OPN, and suggests a basic involvement of OPN action in these conditions. In the case of secondary retrograde or transneuronal degeneration, OPN may have a protective role as intracellular actor. PMID:20522649

Macaque Pontine Omnipause Neurons Play No Direct Role in the Generation of Eye Blinks

PubMed Central

Schultz, K. P.; Williams, C. R.

2010-01-01

We recorded the activity of pontine omnipause neurons (OPNs) in two macaques during saccadic eye movements and blinks. As previously reported, we found that OPNs fire tonically during fixation and pause about 15 ms before a saccadic eye movement. In contrast, for blinks elicited by air puffs, the OPNs paused <2 ms before the onset of the blink. Thus the burst in the agonist orbicularis oculi motoneurons (OOMNs) and the pause in the antagonist levator palpabrae superioris motoneurons (LPSMNs) necessarily precede the OPN pause. For spontaneous blinks there was no correlation between blink and pause onsets. In addition, the OPN pause continued for 40–60 ms after the time of the maximum downward closing of the eyelids, which occurs around the end of the OOMN burst of firing. LPSMN activity is not responsible for terminating the OPN pause because OPN resumption was very rapid, whereas the resumption of LPSMN firing during the reopening phase is gradual. OPN pause onset does not directly control blink onset, nor does pause offset control or encode the transition between the end of the OOMN firing and the resumption of the LPSMNs. The onset of the blink-related eye transients preceded both blink and OPN pause onsets. Therefore they initiated while the saccadic short-lead burst neurons were still fully inhibited by the OPNs and cannot be saccadic in origin. The abrupt dynamic change of the vertical eye transients from an oscillatory behavior to a single time constant exponential drift predicted the resumption of the OPNs. PMID:20164389

Considerable variation in the concentration of osteopontin in human milk, bovine milk, and infant formulas.

PubMed

Schack, L; Lange, A; Kelsen, J; Agnholt, J; Christensen, B; Petersen, T E; Sørensen, E S

2009-11-01

Osteopontin (OPN) is a multifunctional bioactive protein that is implicated in numerous biological processes such as bone remodeling, inhibition of ectopic calcification, and cellular adhesion and migration, as well as several immune functions. Osteopontin has cytokine-like properties and is a key factor in the initiation of T helper 1 immune responses. Osteopontin is present in most tissues and body fluids, with the highest concentrations being found in milk. In the present study, ELISA for human and bovine milk OPN were developed and OPN concentration in human breast milk, bovine milk, and infant formulas was measured and compared. The OPN concentration in human milk was measured to approximately 138 mg/L, which corresponds to 2.1% (wt/wt) of the total protein in human breast milk. This is considerably higher than the corresponding OPN concentrations in bovine milk (approximately 18 mg/L) and infant formulas (approximately 9 mg/L). Moreover, bovine milk OPN is shown to induce the expression of the T helper 1 cytokine IL-12 in cultured human lamina propria mononuclear cells isolated from intestinal biopsies. Finally, the OPN concentration in plasma samples from umbilical cords, 3-mo-old infants, and pregnant and nonpregnant adults was measured. The OPN level in plasma from 3-mo-old infants and umbilical cords was found to be 7 to 10 times higher than in adults. Thus, the high levels of OPN in milk and infant plasma suggest that OPN is important to infants and that ingested milk OPN is likely to induce cytokine production in neonate intestinal immune cells.

Effectiveness of green tea tannin on rats with chronic renal failure.

PubMed

Yokozawa, T; Chung, H Y; He, L Q; Oura, H

1996-06-01

The effects of green tea tannin on nephrectomized rats were examined. There were increases in blood urea nitrogen, serum creatinine, and urinary protein, and a decrease in creatinine clearance in the nephrectomized control rats, whereas better results for these parameters were obtained in rats given green tea tannin after nephrectomy, demonstrating a suppressed progression of the renal failure. When the renal parenchyma was partially resected, the remnant kidney showed a decrease in the activity of radical scavenger enzymes. Green tea tannin, however, was found to lighten the kidney under such oxidative stress. Mesangial proliferation and glomerular sclerotic lesions, which were conspicuous in the rats that were not given green tea tannin after nephrectomy, were also relieved.

Suppression of tumour growth by orally administered osteopontin is accompanied by alterations in tumour blood vessels.

PubMed

Rittling, S R; Wejse, P L; Yagiz, K; Warot, G A; Hui, T

2014-03-04

The integrin-binding protein osteopontin is strongly associated with tumour development, yet is an abundant dietary component as a constituent of human and bovine milk. Therefore, we tested the effect of orally administered osteopontin (o-OPN) on the development of subcutaneous tumours in mice. Bovine milk osteopontin was administered in drinking water to tumour-bearing immune-competent mice. Tumour growth, proliferation, necrosis, apoptosis and blood vessel size and number were measured. Expression of the α₉ integrin was determined. o-OPN suppressed tumour growth, increased the extent of necrosis, and induced formation of abnormally large blood vessels. Anti-OPN reactivity detected in the plasma of OPN-null mice fed OPN suggested that tumour-blocking peptides were absorbed during digestion, but the o-OPN effect was likely distinct from that of an RGD peptide. Expression of the α₉ integrin was detected on both tumour cells and blood vessels. Potential active peptides from the α₉ binding site of OPN were identified by mass spectrometry following in vitro digestion, and injection of these peptides suppressed tumour growth. These results suggest that peptides derived from o-OPN are absorbed and interfere with tumour growth and normal vessel development. o-OPN-derived peptides that target the α₉ integrin are likely involved.

[Expression of OPN gene during different lactation stages in mammary gland of dairy goat and its effect on growth of MCF-7 cell line].

PubMed

Sun, Jie; Luo, Jun; Liu, Jun-Xia; Li, Da-Quan

2009-08-01

To investigate the expression pattern and preliminary function of OPN gene in mammary gland of dairy goat during different lactation stages, using b-actin gene as the internal control, the SYBR Green quantitative real-time PCR (QPCR) analysis was conducted to determine the mRNA expression of OPN gene in mammary gland at the 28th, 60th, 100th, 190th, 270th and 330th day after kidding. Recombinant plasmid of pcDNA3.1-OPN was constructed by inserting the fragment of OPN gene into eukaryotic expression vector pcDNA3.1 and used to transfect the MCF-7 cell line following the restrictive endonuclease cleavage and sequence identification of the target gene segment, the effect of OPN gene on MCF-7 cell proliferation was assessed by MTT analysis. The results indicated that OPN gene exhibited the higher expression level in early (28 d) and late (190 d) lactation stages and the lowest level at dry stage (330 d), which demonstrated a high-low-high-low pattern. There was a significant difference (P < 0. 05) in the proliferation between OPN gene transfected and non-transfected MCF-7 cells, which suggested that the expression of OPN gene could stimulate the proliferation of MCF-7 cells.

Inhibition of osteopontin reduce the cardiac myofibrosis in dilated cardiomyopathy via focal adhesion kinase mediated signaling pathway.

PubMed

Zhao, Hui; Wang, Wei; Zhang, Jie; Liang, Tuo; Fan, Guang-Pu; Wang, Zhi-Wei; Zhang, Pei-De; Wang, Xu; Zhang, Jing

2016-01-01

Osteopontin (OPN) is a pleiotropic cytokine, which has been shown to a close relationship with cardiac fibrosis. Overexpression of OPN in cardiomyocytes induces dilated cardiomyopathy (DCM). This research is to study whether inhibition of OPN could reduce myocardial remodelling in DCM, and if this process is focal adhesion kinase (FAK) dependent, which is recently found an important signal molecule in fibrosis. Eight-week-old cTnTR 141W transgenic mouse of DCM were injected with OPN-shRNA in left ventricular free wall, which could inhibit the OPN expression. Six weeks later, echocardiographic examinations were performed to test left ventricle function and heart tissues were harvested to test the quality of FAK by western blot and severity of fibrosis by masson staining. Human cardiac fibroblast was administrated with OPN, and FAK inhibition by PP2 was treated 2 h before OPN was given. Expression of α-SMA and collagen-I were tested by western blot and real-time PCR assay. OPN-shRNA group has a relatively high ejection fraction (EF), fractional shortening (FS), LV free wall thickness and a less sever cardiac fibrosis. In vitro, OPN could increase collagen-I and α-SMA expression, and this process can be inhibited by FAK inhibitor. Inhibition of OPN could reduce the LV remodeling and dysfunction in DCM mice, which may attribute to the suppression of collagen-I secretion in fibroblast through a FAK/Akt dependent pathway.

Modulation of calcium oxalate dihydrate growth by selective crystal-face binding of phosphorylated osteopontin and polyaspartate peptide showing occlusion by sectoral (compositional) zoning.

PubMed

Chien, Yung-Ching; Masica, David L; Gray, Jeffrey J; Nguyen, Sarah; Vali, Hojatollah; McKee, Marc D

2009-08-28

Calcium oxalate dihydrate (COD) mineral and the urinary protein osteopontin/uropontin (OPN) are commonly found in kidney stones. To investigate the effects of OPN on COD growth, COD crystals were grown with phosphorylated OPN or a polyaspartic acid-rich peptide of OPN (DDLDDDDD, poly-Asp(86-93)). Crystals grown with OPN showed increased dimensions of the {110} prismatic faces attributable to selective inhibition at this crystallographic face. At high concentrations of OPN, elongated crystals with dominant {110} faces were produced, often with intergrown, interpenetrating twin crystals. Poly-Asp(86-93) dose-dependently elongated crystal morphology along the {110} faces in a manner similar to OPN. In crystal growth studies using fluorescently tagged poly-Asp(86-93) followed by imaging of crystal interiors using confocal microscopy, sectoral (compositional) zoning in COD was observed resulting from selective binding and incorporation (occlusion) of peptide exclusively into {110} crystal sectors. Computational modeling of poly-Asp(86-93) adsorption to COD {110} and {101} surfaces also suggests increased stabilization of the COD {110} surface and negligible change to the natively stable {101} surface. Ultrastructural, colloidal-gold immunolocalization of OPN by transmission electron microscopy in human stones confirmed an intracrystalline distribution of OPN. In summary, OPN and its poly-Asp(86-93) sequence similarly affect COD mineral growth; the {110} crystallographic faces become enhanced and dominant attributable to {110} face inhibition by the protein/peptide, and peptides can incorporate into the mineral phase. We, thus, conclude that the poly-Asp(86-93) domain is central to the OPN ability to interact with the {110} faces of COD, where it binds to inhibit crystal growth with subsequent intracrystalline incorporation (occlusion).

Osteopontin expression is correlated with differentiation and good prognosis in medullary thyroid carcinoma.

PubMed

Ferreira, Luciana Bueno; Eloy, Catarina; Pestana, Ana; Lyra, Joana; Moura, Margarida; Prazeres, Hugo; Tavares, Catarina; Sobrinho-Simões, Manuel; Gimba, Etel; Soares, Paula

2016-04-01

Osteopontin (OPN) or secreted phosphoprotein 1 (SPP1) is a matricellular glycoprotein whose expression is elevated in various types of cancer and has been shown to be involved in tumourigenesis and metastasis in many malignancies, including follicular cell-derived thyroid carcinomas. Its role in C-cell-derived thyroid lesions and tumours remains to be established. The objective of this study is to clarify the role of OPN expression in the development of medullary thyroid carcinoma (MTC). OPN expression was analysed in a series of 116 MTCs by immunohistochemistry and by qPCR mRNA quantification of the 3 OPN isoforms (OPNa, OPNb and OPNc) in six cases from which fresh frozen tissue was available. Statistical tests were used to evaluate the relationship of OPN expression and the clinicopathological and molecular characteristics of patients and tumours. OPN expression was detected in 91 of 116 (78.4%) of the MTC. We also observed high OPN expression in C-cell hyperplasia as well as in C-cells scattered in the thyroid parenchyma adjacent to the tumours. OPN expression was significantly associated with smaller tumour size, PTEN nuclear expression and RAS status, and suggestively associated with non-invasive tumours. OPNa isoform was expressed significantly at higher levels in tumours than in non-tumour samples. OPNb and OPNc presented similar levels of expression in all samples. Furthermore, OPNa isoform overexpression was significantly associated with reduced growth and viability in the MTC-derived cell line (TT). The expression of OPN in normal C-cells and C-cell hyperplasia suggests that OPN is a differentiation marker of C-cells, rather than a marker of biological aggressiveness in this setting. At variance with other cancers, OPN expression is associated with good prognostic features in MTC. © 2016 European Society of Endocrinology.

Early onset and differential temporospatial expression of melanopsin isoforms in the developing chicken retina.

PubMed

Verra, Daniela M; Contín, Maria Ana; Hicks, David; Guido, Mario E

2011-07-07

Retinal ganglion cells (RGCs) expressing the photopigment melanopsin (Opn4) display intrinsic photosensitivity. In this study, the presence of nonvisual phototransduction cascade components in the developing chicken retina and primary RGCs cultures was investigated, focusing on the two Opn4 genes: the Xenopus (Opn4x) and the mammalian (Opn4m) orthologs. Retinas were dissected at different embryonic (E) and postnatal (P) days, and primary RGC cultures were obtained at E8 and kept for 1 hour to 5 days. Samples were processed for RT-PCR and immunochemistry. Embryonic retinas expressed the master eye gene Pax6, the prospective RGC specification gene Brn3, and components of the nonvisual phototransduction cascade, such as Opn4m and the G protein q (Gq) mRNAs at very early stages (E4-E5). By contrast, expression of photoreceptor cell markers (CRX, red-opsin, rhodopsin, and α-transducin) was observed from E7 to E12. Opn4m protein was visualized in the whole retina as early as E4 and remained elevated from E6 to the postnatal days, whereas Opn4x was weakly detected at E8 and highly expressed after E11. RGC cultures expressed Gq mRNA, as well as both Opn4 mRNAs and proteins. Opn4m was restricted exclusively to the GC layer at all ages, whereas Opn4x was limited to the forming GC layer and optic nerve at E8, but by E15, its expression was mostly in Prox1(+) horizontal cells. The early expression onset of nonvisual phototransduction molecules could confer premature photosensitivity to RGCs, while the appearance of Opn4x expression in horizontal cells suggests the identification of a novel type of photosensitive cell in birds.

SIRT1 overexpression protects non-small cell lung cancer cells against osteopontin-induced epithelial-mesenchymal transition by suppressing NF-κB signaling.

PubMed

Li, Xuejiao; Jiang, Zhongxiu; Li, Xiangmin; Zhang, Xiaoye

2018-01-01

Osteopontin (OPN) is a promoter for tumor progression. It has been reported to promote non-small cell lung cancer (NSCLC) progression via the activation of nuclear factor-κB (NF-κB) signaling. As the increased acetylation of NF-κB p65 is linked to NF-κB activation, the regulation of NF-κB p65 acetylation could be a potential treatment target for OPN-induced NSCLC progression. Sirtuin 1 (SIRT1) is a deacetylase, and the role of SIRT1 in tumor progression is still controversial. The effect and mechanism of SIRT1 on OPN-induced tumor progression remains unknown. The results presented in this research demonstrated that OPN inhibited SIRT1 expression and promoted NF-κB p65 acetylation in NSCLC cell lines (A549 and NCI-H358). In this article, overexpression of SIRT1 was induced by infection of SIRT1-overexpressing lentiviral vectors. The overexpression of SIRT1 protected NSCLC cells against OPN-induced NF-κB p65 acetylation and epithelial-mesenchymal transition (EMT), as indicated by the reduction of OPN-induced changes in the expression levels of EMT-related markers and cellular morphology. Furthermore, SIRT1 overexpression significantly attenuated OPN-induced cell proliferation, migration and invasion. Moreover, overexpression of SIRT1 inhibited OPN-induced NF-κB activation. As OPN induced NSCLC cell EMT through activation of NF-κB signaling, OPN-induced SIRT1 downregulation may play an important role in NSCLC cell EMT via NF-κB signaling. The results suggest that SIRT1 could be a tumor suppressor to attenuate OPN-induced NSCLC progression through the regulation of NF-κB signaling.

Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial

PubMed Central

2014-01-01

Introduction Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis. Methods We measured OPN in plasma by ELISA, and in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/− octreotide in a randomized trial (NCIC CTG MA.14; National Cancer Institute of Canada Clinical Trials Group Mammary.14). Results Plasma OPN was measured in 2,540 samples; 688 at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46 ng/ml (range 22.6 to 290) which did not differ from normal levels. Mean percentage OPN tumor cell positivity was 33.9 (95% CI: 30.2 to 37.9). There was no correlation between plasma and tumor OPN values. In multivariate analysis, neither was associated with event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9 to 543) in the recurrence period compared with baseline levels. Conclusions The hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, our finding of elevated mean OPN plasma level around the time of recurrence warrants further study. Trial registration NCT00002864, http://clinicaltrials.gov/show/NCT00002864 PMID:24451146

Upregulation of osteopontin expression via the interaction of macrophages and fibroblasts under IL-1b stimulation.

PubMed

Shimodaira, Takahiro; Matsuda, Kazuyuki; Uchibori, Takaaki; Sugano, Mitsutoshi; Uehara, Takeshi; Honda, Takayuki

2018-04-25

Fibrosis is attributed to dysregulation of tissue-remodeling. In remodeling areas, fibroblasts and macrophages actively make contact with each other. Osteopontin (OPN) is a pro-fibrotic molecule, whose expression is upregulated by interleukin (IL)-1β via secretion of its downstream cytokines, such as IL-6. Here, we investigated the effect of interaction between fibroblasts and macrophages under IL-1β stimulation on the expression of OPN. We used human lung fibroblasts and THP-1 macrophages differentiated from THP-1 cells using phorbol 12-myristate 13-acetate. These cells were either cultured alone or co-cultured under IL-1β stimulation. Secretion of OPN and IL-6 were examined by enzyme-linked immunosorbent assay, and mRNA expression was assessed by quantitative real-time PCR. The effects of siRNA against IL-6 or OPN on OPN expression were evaluated. OPN expression increased when fibroblasts and THP-1 macrophages were co-cultured under IL-1β stimulation. The siRNA against IL-6 in fibroblasts suppressed the upregulation of OPN expression during co-culture, whereas siRNA against IL-6 in THP-1 macrophages did not. The upregulation of expression of OPN mRNA in fibroblasts or THP-1 macrophages when co-cultured under IL-1β stimulation was mediated by IL-6 from fibroblasts. OPN from THP-1 macrophages was involved in the increase of OPN expression in fibroblasts. The present study revealed the crosstalk between fibroblasts and THP-1 macrophages under IL-1β stimulation, where IL-6 from fibroblasts, stimulated by IL-1β, upregulated OPN expression in fibroblasts themselves via increase in OPN from THP-1 macrophages. The fibroblasts/macrophages network may induce activation or qualitative changes in both cells, which contributes to inflammation-associated fibrosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Treatment of patients with metastatic renal cell carcinoma undergoing hemodialysis: case report of two patients and short literature review

PubMed Central

2013-01-01

Background Renal cell carcinoma (RCC) may involve both kidneys. When bilateral nephrectomy is necessary renal replacement therapy is mandatory. Treating such patients with sequential therapy based on cytokines, antiangiogenic factors and mammalian target of rapamycin (mTOR) inhibitors is challenging. Case presentation The first case, a 50-year-old Caucasian female, underwent a radical right nephrectomy for RCC. Twelve years later she underwent a radical left nephrectomy along with total hysterectomy including bilateral salpingo-oophorectomy for RCC involving the right kidney and ovary. Hemodialysis was necessary because of bilateral nephrectomy. She relapsed with pulmonary metastases and enlarged mediastinal lymph nodes and received cytokine based therapy along with bevacizumab. Therapy was discontinued despite the partial response because of hemorrhagic gastritis. Therapy was switched to an antiangiogenic factor but the patient manifested a parietal brain hematoma and stopped therapy. Subsequently disease relapsed with malignant pleural effusion and pulmonary nodules and a mammalian target of rapamycin inhibitor was administered which was withdrawn only at patient’s deteriorating performance status. The patient died of the disease 13 years after the initial diagnosis of RCC. The second case, a 51-year-old, Caucasian male, underwent a radical right nephrectomy for a chromophobe RCC. Six months later he underwent a radical left nephrectomy for RCC that proved to be a clear cell RCC. Due to bilateral nephrectomy hemodialysis was obligatory. Following disease recurrence at the anatomical bed of the right kidney therapy with antiangiogenic factor was administered which led to disease regression. However the patient experienced a left temporal-occipital brain hematoma. A radical excision of the recurrence which histologically proved to be a chromophobe RCC was not achieved and the patient received mTOR inhibitor which led to disease complete response. Nine years after the initial diagnosis of RCC he is disease free and leads an active life. Conclusion Patients with RCC are in significant risk to manifest bilateral disease. Renal insufficiency requiring hemodialysis poses therapeutic challenges. Clinicians must be aware of the antiangiogenic factors’ adverse effects, especially bleeding, that may manifest in higher frequency and more severe in this setting. PMID:23587009

Retroperitoneal Laparoscopic Partial Nephrectomy Versus Radical Nephrectomy for Clinical T1 Renal Hilar Tumor: Comparison of Perioperative Characteristics and Short-Term Functional and Oncologic Outcomes.

PubMed

Yang, Chuance; Wang, Zhenlong; Huang, Shanlong; Xue, Li; Fu, Delai; Chong, Tie

2018-04-18

To present our single-center experience with retroperitoneal laparoscopic partial nephrectomy (LPN) and retroperitoneal laparoscopic radical nephrectomy (LRN) for T1 renal hilar tumors and evaluate which one is better. A retrospective review of 63 patients with hilar tumors undergoing retroperitoneal LPN or LRN was performed. The perioperative characteristics, change in estimated glomerular filtration rate (eGFR) from baseline to month 3, and oncologic outcomes were summarized. In total, 25 patients underwent LPN, and 38 patients underwent LRN. The mean tumor size in the LPN and LRN groups was 4.5 and 4.9 cm, respectively. The mean operation time was longer in the LPN group than that in the LRN group (212.5 minutes versus 160.7 minutes, respectively; P < .05). Patients undergoing the LPN had a longer median length of hospital stay after surgery (9 days versus 7 days, P < .05). Four percent of patients in the LPN group experienced postoperative complications compared with 5% of patients in the LRN group, which was not significantly different. Compared with preoperative eGFR, postoperative eGFR at 3 months decreased by 15.2 mL/min/1.73 m 2 and 27.8 mL/min/1.73 m 2 in the LPN and the LRN groups, respectively (P < .05). There was one local recurrence in the LPN group and three local or distant recurrences in the LRN group (P > .05). In experienced hands, although retroperitoneal LRN can result in shorter operation times and shorter lengths of stay, retroperitoneal LPN can preserve renal function better than LRN. Retroperitoneal LPN should be the priority in selected patients with T1 renal hilar tumors, especially for patients with renal insufficiency.

The Management of Synchronous Bilateral Wilms Tumor: A Report from the National Wilms Tumor Study Group

PubMed Central

Hamilton, Thomas E.; Ritchey, Michael L.; Haase, Gerald M.; Argani, Pedram; Peterson, Susan M.; Anderson, James R.; Green, Daniel M.; Shamberger, Robert C.

2013-01-01

Objective To provide guidelines for future trials, we reviewed the outcomes of children with synchronous bilateral Wilms tumors (BWT) treated on National Wilms Tumor Study-4 (NWTS-4). Methods NWTS-4 enrolled 3,335 patients (pts) including 188 pts with BWT (5.6%). Treatment and outcome data were collected. Results Among 188 BWT pts registered with NWTS-4, 195 kidneys in 123 patients had initial open biopsy, 44 kidneys in 31 pts had needle biopsies. Although pre-resection chemotherapy was recommended, 87 kidneys in 83 pts were managed with primary resection: Complete nephrectomy 48 in 48 pts, 31 partial/wedge nephrectomies in 27 pts, enucleations 8 in 8 pts. No initial surgery was performed in 45 kidneys in 43 pts, 5 kidneys in 3 pts not coded. Anaplasia was diagnosed after completion of the initial course of chemotherapy in 14 pts (initial surgical procedure: 9 open biopsies, 4 needle biopsies, 1 partial nephrectomy). The average number of days from the start of chemotherapy to diagnosis of anaplasia was 390 (range 44–1,925 days). Relapse or progression of disease occurred in 54 children. End stage renal failure occurred in 23 children, 6 of whom had bilateral nephrectomies. The 8 year event free survival (EFS) for BWT with favorable histology was 74%, and overall survival (OS) was 89%; while the EFS for BWT with unfavorable histology was 40%, OS was 45%. Conclusion The current analysis of patients with BWT treated on NWTS-4 shows that preservation of renal parenchyma is possible in many pts following initial preoperative chemotherapy. The incidence of end-stage renal disease remains significantly higher in children with BWT. Future studies are warranted to address the need for earlier biopsy in non-responsive tumors and earlier definitive surgery to recognize unfavorable histology in these high risk patients. PMID:21394016

Robotic Laparoendoscopic Single-site Retroperitioneal Renal Surgery: Initial Investigation of a Purpose-built Single-port Surgical System.

PubMed

Maurice, Matthew J; Ramirez, Daniel; Kaouk, Jihad H

2017-04-01

Robotic single-site retroperitoneal renal surgery has the potential to minimize the morbidity of standard transperitoneal and multiport approaches. Traditionally, technological limitations of non-purpose-built robotic platforms have hindered the application of this approach. To assess the feasibility of retroperitoneal renal surgery using a new purpose-built robotic single-port surgical system. This was a preclinical study using three male cadavers to assess the feasibility of the da Vinci SP1098 surgical system for robotic laparoendoscopic single-site (R-LESS) retroperitoneal renal surgery. We used the SP1098 to perform retroperitoneal R-LESS radical nephrectomy (n=1) and bilateral partial nephrectomy (n=4) on the anterior and posterior surfaces of the kidney. Improvements unique to this system include enhanced optics and intelligent instrument arm control. Access was obtained 2cm anterior and inferior to the tip of the 12th rib using a novel 2.5-cm robotic single-port system that accommodates three double-jointed articulating robotic instruments, an articulating camera, and an assistant port. The primary outcome was the technical feasibility of the procedures, as measured by the need for conversion to standard techniques, intraoperative complications, and operative times. All cases were completed without the need for conversion. There were no intraoperative complications. The operative time was 100min for radical nephrectomy, and the mean operative time was 91.8±18.5min for partial nephrectomy. Limitations include the preclinical model, the small sample size, and the lack of a control group. Single-site retroperitoneal renal surgery is feasible using the latest-generation SP1098 robotic platform. While the potential of the SP1098 appears promising, further study is needed for clinical evaluation of this investigational technology. In an experimental model, we used a new robotic system to successfully perform major surgery on the kidney through a single small incision without entering the abdomen. Copyright © 2016. Published by Elsevier B.V.

The financial impact of robotic technology for partial and radical nephrectomy.

PubMed

Kates, Max; Ball, Mark W; Patel, Hiten D; Gorin, Michael A; Pierorazio, Phillip M; Allaf, Mohamad E

2015-03-01

We sought to evaluate the financial impact of robotic technology for partial nephrectomy (PN) and radical nephrectomy (RN) in the state of Maryland. The Maryland Health Services Cost Review Commission (HSCRC) documents all acute care hospital charges data. This database was queried for patients who underwent laparoscopic or robot-assisted RN and PN from 2008 to 2012. Total hospital charge, subcharge, and length of stay (LOS) were analyzed separately for RN and PN. Overall, 2834 patients were identified. Of those, 282 were laparoscopic PN (LPN), 1078 robot-assisted PN (RPN), 1098 laparoscopic RN (LRN), and 376 robot-assisted RN (RRN). For PN, the total hospital charge was $19,062 for LPN and $18,255 for RPN (P=0.138), with a charge savings of $807 per case in favor of robotics. For RN, the total hospital charge was $23,391 for RRN and $18,280 for LRN (P=0.004), with a charge premium of $5111 for robotic cases. LOS was shorter for RPN compared with LPN (2.51 vs 2.99 days, P<0.0001) and for RRN compared with LRN (3.52 vs 3.98, P=0.0498). RPN is associated with lower hospital charges than LPN, while RRN is associated with higher hospital charges than LRN. Savings for RPN are driven by decreased room and board charge, while the premium for RRN is driven by higher operating room and supply charges. Because RRN use is increasing, the financial implications of RRN use for routine cases warrants further study.

Osteopontin Mediates Citrobacter rodentium-Induced Colonic Epithelial Cell Hyperplasia and Attaching-Effacing Lesions

PubMed Central

Wine, Eytan; Shen-Tu, Grace; Gareau, Mélanie G.; Goldberg, Harvey A.; Licht, Christoph; Ngan, Bo-Yee; Sorensen, Esben S.; Greenaway, James; Sodek, Jaro; Zohar, Ron; Sherman, Philip M.

2010-01-01

Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN+/+ and OPN−/− fibroblasts were incubated with C. rodentium and attaching-effacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN−/− mice, and spleen enlargement by infection was absent in OPN−/− mice. Rectal administration of OPN to OPN−/− mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN−/− mice, compared with wild-type mice, which was accompanied by reduced attaching–effacing lesions, both in infected OPN−/− mice and OPN−/− mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN−/− cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses. PMID:20651246

De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy

PubMed Central

Buena-Atienza, Elena; Rüther, Klaus; Baumann, Britta; Bergholz, Richard; Birch, David; De Baere, Elfride; Dollfus, Helene; Greally, Marie T.; Gustavsson, Peter; Hamel, Christian P.; Heckenlively, John R.; Leroy, Bart P.; Plomp, Astrid S.; Pott, Jan Willem R.; Rose, Katherine; Rosenberg, Thomas; Stark, Zornitza; Verheij, Joke B. G. M.; Weleber, Richard; Zobor, Ditta; Weisschuh, Nicole; Kohl, Susanne; Wissinger, Bernd

2016-01-01

X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of ≥20% of transcripts including the known pathogenic haplotypes (i.e. ‘LIAVA’, ‘LVAVA’) with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the ‘LIAVA’ haplotype derived from an ancestral less deleterious ‘LIAVS’ haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree. PMID:27339364

Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice

PubMed Central

Bruemmer, Dennis; Collins, Alan R.; Noh, Grace; Wang, Wei; Territo, Mary; Arias-Magallona, Sarah; Fishbein, Michael C.; Blaschke, Florian; Kintscher, Ulrich; Graf, Kristof; Law, Ronald E.; Hsueh, Willa A.

2003-01-01

Osteopontin (OPN) is expressed in atherosclerotic lesions, particularly in diabetic patients. To determine the role of OPN in atherogenesis, ApoE–/–OPN+/+, ApoE–/–OPN+/–, and ApoE–/–OPN–/– mice were infused with Ang II, inducing vascular OPN expression and accelerating atherosclerosis. Compared with ApoE–/–OPN+/+ mice, ApoE–/–OPN+/– and ApoE–/–OPN–/– mice developed less Ang II–accelerated atherosclerosis. ApoE–/– mice transplanted with bone marrow derived from ApoE–/–OPN–/– mice had less Ang II–induced atherosclerosis compared with animals receiving ApoE–/–OPN+/+ cells. Aortae from Ang II–infused ApoE–/–OPN–/– mice expressed less CD68, C-C-chemokine receptor 2, and VCAM-1. In response to intraperitoneal thioglycollate, recruitment of leukocytes in OPN–/– mice was impaired, and OPN–/– leukocytes exhibited decreased basal and MCP-1–directed migration. Furthermore, macrophage viability in atherosclerotic lesions from Ang II–infused ApoE–/–OPN–/– mice was decreased. Finally, Ang II–induced abdominal aortic aneurysm formation in ApoE–/–OPN–/– mice was reduced and associated with decreased MMP-2 and MMP-9 activity. These data suggest an important role for leukocyte-derived OPN in mediating Ang II–accelerated atherosclerosis and aneurysm formation. PMID:14597759

Interleukin-6 enhances cancer stemness and promotes metastasis of hepatocellular carcinoma via up-regulating osteopontin expression.

PubMed

Wang, Chao-Qun; Sun, Hao-Ting; Gao, Xiao-Mei; Ren, Ning; Sheng, Yuan-Yuan; Wang, Zheng; Zheng, Yan; Wei, Jin-Wang; Zhang, Kai-Li; Yu, Xin-Xin; Zhu, Yin; Luo, Qin; Yang, Lu-Yu; Dong, Qiong-Zhu; Qin, Lun-Xiu

2016-01-01

Interleukin-6 (IL-6), one of the most important inflammatory cytokines, plays a pivotal role in metastasis and stemness of solid tumors. However, the underlying mechanisms of IL-6 in HCC metastasis remain unclear. In the present study, we demonstrated that stemness and metastatic potential of HCC cells were significantly enhanced after IL-6 stimulation. IL-6 could induce expression of osteopontin (OPN), along with other stemness-related genes, including HIF1α, BMI1, and HEY1. Block of OPN induction could significantly abrogate the effect of IL-6 on stemness and metastasis of HCC cells. Furthermore, IL-6 level was positively correlated with OPN in HCC. Patients with high plasma IL-6 or OPN level had poorer prognosis. In multivariate analysis, IL-6 and OPN were demonstrated to be independent prognostic indicators for HCC patients, and their combination had a better prognostic performance than IL-6 or OPN alone. Collectively, our findings indicate that IL-6 could enhance stemness and promote metastasis of HCC via up-regulating OPN expression, which can be a potential therapeutic target for combating HCC metastasis, and the combination of IL-6 and OPN serves as a promising prognostic predictor for HCC.

Sympathetic control of bone mass regulated by osteopontin

PubMed Central

Nagao, Masashi; Feinstein, Timothy N.; Ezura, Yoichi; Hayata, Tadayoshi; Notomi, Takuya; Saita, Yoshitomo; Hanyu, Ryo; Hemmi, Hiroaki; Izu, Yayoi; Takeda, Shu; Wang, Kathryn; Rittling, Susan; Nakamoto, Tetsuya; Kaneko, Kazuo; Kurosawa, Hisashi; Karsenty, Gerard; Denhardt, David T.; Vilardaga, Jean-Pierre; Noda, Masaki

2011-01-01

The sympathetic nervous system suppresses bone mass by mechanisms that remain incompletely elucidated. Using cell-based and murine genetics approaches, we show that this activity of the sympathetic nervous system requires osteopontin (OPN), a cytokine and one of the major members of the noncollagenous extracellular matrix proteins of bone. In this work, we found that the stimulation of the sympathetic tone by isoproterenol increased the level of OPN expression in the plasma and bone and that mice lacking OPN (OPN-KO) suppressed the isoproterenol-induced bone loss by preventing reduced osteoblastic and enhanced osteoclastic activities. In addition, we found that OPN is necessary for changes in the expression of genes related to bone resorption and bone formation that are induced by activation of the sympathetic tone. At the cellular level, we showed that intracellular OPN modulated the capacity of the β2-adrenergic receptor to generate cAMP with a corresponding modulation of cAMP-response element binding (CREB) phosphorylation and associated transcriptional events inside the cell. Our results indicate that OPN plays a critical role in sympathetic tone regulation of bone mass and that this OPN regulation is taking place through modulation of the β2-adrenergic receptor/cAMP signaling system. PMID:21990347

Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior

PubMed Central

Ferreira, Luciana Bueno; Tavares, Catarina; Pestana, Ana; Pereira, Catarina Leite; Eloy, Catarina; Pinto, Marta Teixeira; Castro, Patricia; Batista, Rui; Rios, Elisabete; Sobrinho-Simões, Manuel; Pereira Gimba, Etel Rodrigues; Soares, Paula

2016-01-01

Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches. PMID:27409830

Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior.

PubMed

Ferreira, Luciana Bueno; Tavares, Catarina; Pestana, Ana; Pereira, Catarina Leite; Eloy, Catarina; Pinto, Marta Teixeira; Castro, Patricia; Batista, Rui; Rios, Elisabete; Sobrinho-Simões, Manuel; Gimba, Etel Rodrigues Pereira; Soares, Paula

2016-08-09

Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches.

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

PubMed Central

Bayrle, Corinna; Wetzke, Martin; Fries, Christoph; Tillack, Cornelia; Olszak, Torsten; Beigel, Florian; Steib, Christian; Friedrich, Matthias; Diegelmann, Julia; Czamara, Darina; Brand, Stephan

2011-01-01

Background Osteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease (IBD). The aim of our study was to analyze the association of osteopontin (OPN/SPP1) gene variants in a large cohort of IBD patients. Methodology/Principal Findings Genomic DNA from 2819 Caucasian individuals (n = 841 patients with Crohn's disease (CD), n = 473 patients with ulcerative colitis (UC), and n = 1505 healthy unrelated controls) was analyzed for nine OPN SNPs (rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138). Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs (rs4754, rs1126616, rs1126772 and rs9138), we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients (p = 0.0004, OR = 0.69). None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 (omnibus p-value = 2.07×10−8). Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10−5). There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 (p = 4.18×10−2) and between OPN SNP rs1126616 and IL23R SNP rs2201841 (p = 4.18×10−2) but none of these associations remained significant after Bonferroni correction. Conclusions/Significance Our study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion. PMID:22242114

Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis.

PubMed

Agah, Elmira; Zardoui, Arshia; Saghazadeh, Amene; Ahmadi, Mona; Tafakhori, Abbas; Rezaei, Nima

2018-01-01

Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis (MS) and lead to early management of the disease. Accumulating evidence suggest that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic review and meta-analysis of studies that measured peripheral blood and CSF levels of OPN in MS patients and controls to evaluate the diagnostic potential of this biomarker better. We searched PubMed, Web of Science and Scopus databases to find articles that measured OPN concentration in peripheral blood and CSF samples from MS patients up to October 19, 2016. Q statistic tests and the I2 index were applied for heterogeneity assessment. If the I2 index was less than 40%, the fixed-effects model was used for meta-analysis. Random-effects meta-analysis was chosen if the I2 value was greater than 40%. After removal of duplicates, 918 articles were identified, and 27 of them fulfilled the inclusion criteria. We included 22 eligible studies in the final meta-analysis. MS patients, in general, had considerably higher levels of OPN in their CSF and blood when compared to all types of controls (p<0.05). When the comparisons were made between different subtypes of MS patients and controls, the results pointed to significantly higher levels of OPN in CSF of MS subgroups (p<0.05). All subtypes of MS patients, except CIS patients, had increased blood levels of OPN compared to controls (p<0.05). In the second set of meta-analyses, we compared the peripheral blood and CSF concentrations of OPN between MS patient subtypes. CIS patients had significantly lower levels of OPN both in their peripheral blood and CSF compared to patients with progressive subtypes of MS (p<0.05). CSF concentration of OPN was significantly higher among RRMS patients compared to the CIS patients and SPMS patients (P<0.05). Finally, patients with active MS had significantly higher OPN levels in their CSF compared to patients with stable disease (P = 0.007). The result of this study confirms that increased levels of OPN exist in CSF and peripheral blood of MS patients and strengthens the evidence regarding the clinical utility of OPN as a promising and validated biomarker for MS.

Molecular characterization and expression analysis of osteopontin cDNA from lactating mammary gland in yak (Bos grunniens).

PubMed

Bai, W L; Yang, R J; Yin, R H; Jiang, W Q; Luo, G B; Yin, R L; Zhao, S J; Li, C; Zhao, Z H

2012-04-01

Osteopontin (OPN) is a secreted phosphorylated glycoprotein. It has an important role in mammary gland development and lactation, as well as, is thought to be a potential candidate gene for lactation traits. In the present work, we isolated and characterized a full-length open reading frame (ORF) of yak OPN cDNA from lactating mammary tissue, and examined its expression pattern in mammary gland during different stages of lactation, as well as, the recombinant OPN protein of yak was expressed successfully in E. coli. The sequencing results indicated that the isolated cDNA was 1132-bp in length containing a complete ORF of 837-bp. It encoded a precursor protein of yak OPN consisting of 278 amino acid with a signal peptide of 16 amino acids. Yak OPN has a predicted molecular mass of 29285.975 Da and an isoelectric point of 4.245. It had an identity of 65.50-99.16% in cDNA, identity of 52.06-98.56% and similarity of 65.40-98.56% in deduced amino acids with the corresponding sequences of cattle, buffalo, sheep, goat, pig, human, and rabbit. The phylogenetic analysis indicated that yak OPN had the closest evolutionary relationship with that of cattle, and next buffalo. In mammary gland, yak OPN was generally transcribed in a declining pattern from colostrum period to dry period with an apparent increase of OPN expression being present in the late period of lactation compared with peak period of lactation. Western blot analysis indicated that His-tagged yak OPN protein expressed in E. coli could be recognized not only by an anti-His-tag antibody but also by an anti-human OPN antibody. These results from the present work provided a foundation for further insight into the role of OPN gene in yak lactation.

Robotic renal surgery: The future or a passing curiosity?

PubMed Central

Warren, Jeff; da Silva, Vitor; Caumartin, Yves; Luke, Patrick P.W.

2009-01-01

The development, advancement and clinical integration of robotic technology in surgery continue at a staggering pace. In no other discipline has this rapid evolution occurred to a greater degree than in urology. Although radical prostatectomy has grown to become the prototypical application for the robot, the role of the robot in renal surgery remains controversial. Herein we review the literature on robotic renal surgery. A comprehensive PubMed literature search was performed to identify all published reports relating to robotic renal surgery. All clinically related articles involving human participants were critically appraised in this review. Fifty-one clinical articles were included, encompassing robot-assisted pyeloplasty, nephrectomy, nephroureterectomy, living-donor nephrectomy and partial nephrectomy. Feasibility has been shown for each of these procedures. Robot-assisted techniques have been described for almost all renal-related procedures. However, the intersect between feasibility and necessity as it pertains to robotic renal surgery has yet to be defined. Also, the high cost of surgical robotic technology mandates critical appraisal before adoption, especially in a publicly funded health care system, such as the one present in Canada. PMID:19543471

Increased amount of phosphorylated proinflammatory osteopontin in rheumatoid arthritis synovia is associated to decreased tartrate-resistant acid phosphatase 5B/5A ratio.

PubMed

Luukkonen, Jani; Pascual, Laia Mira; Patlaka, Christina; Lång, Pernilla; Turunen, Sanna; Halleen, Jussi; Nousiainen, Tomi; Valkealahti, Maarit; Tuukkanen, Juha; Andersson, Göran; Lehenkari, Petri

2017-01-01

Osteopontin (OPN) is an immunoregulatory protein which production increases in both rheumatoid arthritis (RA) and osteoarthritis (OA). Phosphorylated osteopontin (Phospho-OPN) is known to increase macrophage and osteoclast activation, this process is controlled by extracellular tartrate-resistant acid phosphatase (TRAcP), also a biomarker for RA. Here, we evaluated the phosphorylation status of OPN in RA and OA synovia, as well as its correlation with TRAcP isoforms. Synovial tissue and fluid were obtained from 24 RA (14 seropositive and 10 seronegative) and 24 OA patients. Western blotting was used to analyze the extent of OPN phosphorylation. TRAcP isoforms were measured in synovial fluid using ELISA; immunohistochemistry assessed the distribution of OPN and TRAcP expressing cells in the synovial tissue, especially distinguishing between the TRAcP isoforms. Full-length OPN was more phosphorylated in RA than in OA (p<0.05). The thrombin cleaved C-terminal end of OPN was also more phosphorylated in RA (p<0.05). RA patients had a lower concentration of TRAcP 5B and higher concentration of less active 5A in their synovial fluid compared to OA patients. The TRAcP 5B/5A ratio was decreased in RA and correlated negatively with the amount of phospho-OPN (p<0.05). TRAcP positive cells for both isoforms were found all along the synovial lining; OPN antibody staining was localized in the extracellular matrix. Our data suggests that in RA the synovial fluid contains insufficient amounts of TRAcP 5B which increase levels of the proinflammatory phospho-OPN. This may lead to increased macrophage and osteoclast activation, resulting in the increased local inflammation and bone resorption present in RA joints.

Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Hong-Bo, E-mail: xhbzhb@yahoo.com; Lu, Xiang-Yang; Sun, Zhi-Liang

Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE{sup -/-}) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effectivemore » concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE{sup -/-} mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. -- Graphical abstract: Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. Highlights: Black-Right-Pointing-Pointer OPN-CD44 pathway plays a critical role in the development of atherosclerosis. Black-Right-Pointing-Pointer We examine lesion area, OPN and CD44 changes after kaempferol treatment. Black-Right-Pointing-Pointer Kaempferol treatment decreased atherosclerotic lesion area in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis.« less

The osteopontin-controlled switching of calcium oxalate monohydrate morphologies in artificial urine provides insights into the formation of papillary kidney stones.

PubMed

Langdon, Aaron; Grohe, Bernd

2016-10-01

The protein osteopontin (OPN) plays an important role in preventing the formation of calcium oxalate monohydrate (COM) kidney stones. To gain insight into these mechanisms, crystallization was induced by addition of human kidney OPN to artificial urine (ionic strength comparable to urine; without citrate), and the OPN-COM interaction studied using a combination of scanning electron (SEM) and confocal microscopy. By SEM, we found that increasing OPN concentrations formed large monoclinic penetration twins (no protein added) and, at higher concentrations (1-, 2μg/ml OPN), super and hyper twins with crystal habits not found in previous studies. For instance, the hyper twins indicate well-facetted gearwheel-like habits with "teeth" developed in all crystallographic directions. At OPN concentrations ≥2μg/ml, a switching to small dumbbell-shaped COM habits with fine-textured surfaces occurred. Confocal microscopy of these dumbbells indicates protein incorporation in almost the entire crystal structure (in contrast to facetted COM), proposing a threshold concentration of ∼2μg/ml OPN for the facetted to the non-facetted habit transformation. Both the gearwheel-like and the dumbbell-shaped habit are again found side-by-side (presumably triggered by OPN concentration gradients within the sample) in in-vitro formed conglomerates, which resemble cross-sections of papillary kidney stones. The abrupt transformation from facetted to non-facetted habits and the unique compliance of the two in-vitro formed habits with the two main morphologies found in papillary kidney stones propose that OPN is a main effector in direct stone-forming processes. Moreover, stone structures which exhibit these two morphologies side-by-side might serve as a novel indicator for OPN concentrations surrounding those structures. Copyright © 2016 Elsevier B.V. All rights reserved.

Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy.

PubMed

Kuraoka, Mutsuki; Kimura, En; Nagata, Tetsuya; Okada, Takashi; Aoki, Yoshitsugu; Tachimori, Hisateru; Yonemoto, Naohiro; Imamura, Michihiro; Takeda, Shin'ichi

2016-05-01

Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Elevated tumor and serum levels of the hypoxia-associated protein osteopontin are associated with prognosis for soft tissue sarcoma patients.

PubMed

Bache, Matthias; Kappler, Matthias; Wichmann, Henri; Rot, Swetlana; Hahnel, Antje; Greither, Thomas; Said, Harun M; Kotzsch, Matthias; Würl, Peter; Taubert, Helge; Vordermark, Dirk

2010-04-08

Osteopontin (OPN) overexpression is correlated with a poor prognosis for tumor patients. However, only a few studies investigated the prognostic impact of expression of OPN in soft tissue sarcomas (STS) yet. This study is based on tumor and serum samples from 93 adult STS patients. We investigated OPN protein levels in serum (n = 86) and tumor tissue (n = 80) by ELISA and OPN mRNA levels in tumor tissue (n = 68) by quantitative real-time PCR. No correlation was found between OPN levels in serum and tumor tissue. Moreover, an elevated OPN protein level in the serum was significantly associated with clinical parameters such as higher stage (p = 0.004), higher grade (p = 0.003), subtype (p = 0.002) and larger tumor size (p = 0.03). OPN protein levels in the tumor tissue were associated with higher stage (p = 0.06), higher grade (p = 0.003), subtype (p = 0.07) and an increased rate of relapse (p = 0.02). In addition, using a Cox's proportional hazards regression model, we found that an elevated OPN protein level in the serum and tumor tissue extracts is a significant negative prognostic factor for patients with STS. The relative risks of tumor-related death were 2.2 (p < 0.05) and 3.7 (p = 0.01), respectively. Our data suggest OPN protein in serum as well as in tumor tissue extracts is an important prognostic factor for soft tissue sarcoma patients.

Microarray analysis of human milk cells: persistent high expression of osteopontin during the lactation period

PubMed Central

NAGATOMO, T; OHGA, S; TAKADA, H; NOMURA, A; HIKINO, S; IMURA, M; OHSHIMA, K; HARA, T

2004-01-01

To continue the search for immunological roles of breast milk, cDNA microarray analysis on cytokines and growth factors was performed for human milk cells. Among the 240 cytokine-related genes, osteopontin (OPN) gene ranked top of the expression. Real-time PCR revealed that the OPN mRNA levels in colostrum cells were approximately 100 times higher than those in PHA-stimulated peripheral blood mononuclear cells (PBMNCs), and 10 000 times higher than those in PB CD14+ cells. The median levels of OPN mRNA in early milk or mature milk cells were more than three times higher than those in colostrum cells. Western blot analysis of human milk showed appreciable expression of full-length and short form proteins of OPN. The concentrations of full-length OPN in early milk or mature milk whey continued to be higher than those in colostrum whey and plasma as assessed by ELISA. The early milk (3–7 days postpartum) contained the highest concentrations of OPN protein, while the late mature milk cells (1 years postpartum) had the highest expression of OPN mRNA of all the lactating periods. The results of immunohistochemical and immunocytochemical staining indicated that OPN-producing epithelial cells and macrophages are found in actively lactating mammary glands. These results suggest that the persistently and extraordinarily high expression of OPN in human milk cells plays a potential role in the immunological development of breast-fed infants. PMID:15373904

A Novel Cryptic Binding Motif, LRSKSRSFQVSDEQY, in the C-Terminal Fragment of MMP-3/7-Cleaved Osteopontin as a Novel Ligand for α9β1 Integrin Is Involved in the Anti-Type II Collagen Antibody-Induced Arthritis

PubMed Central

Kon, Shigeyuki; Nakayama, Yosuke; Matsumoto, Naoki; Ito, Koyu; Kanayama, Masashi; Kimura, Chiemi; Kouro, Hitomi; Ashitomi, Dai; Matsuda, Tadashi; Uede, Toshimitsu

2014-01-01

Osteopontin (OPN) is a multifunctional protein that has been linked to various intractable inflammatory diseases. One way by which OPN induces inflammation is the production of various functional fragments by enzyme cleavage. It has been well appreciated that OPN is cleaved by thrombin, and/or matrix metalloproteinase-3 and -7 (MMP-3/7). Although the function of thrombin-cleaved OPN is well characterized, little is known about the function of MMP-3/7-cleaved OPN. In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA. PMID:25545242

Detection of Osteopontin in the pericyst of human hepatic Echinococcus granulosus.

PubMed

Peng, Xinyu; Li, Jianhui; Wu, Xiangwei; Zhang, Shijie; Niu, Jianhua; Chen, Xiaoping; Yao, Jin; Sun, Hong

2006-12-01

It aims at investigating the expression and distribution of the Osteopontin (OPN) in the pericyst of human hepatic Echinococcus granulosus and their related significances. Sixty pericysts excised by "sub-adventitial cystectomy" were studied. OPN was detected in 80% (48/60) of cysts by Western blotting and distributed in the side of "exocyst" layer directing to the parasite, also macrophages were identified in the vicinity of OPN by immunohistochemistry staining. The coexpression of OPN and CD68 was observed by immunofluorescence double labeling and analyzed by Image-Pro Plus 5.1; with special stain techniques, variable degrees of calcium deposits were observed in 80% (48/60) cysts, and the calcium deposits concurrencely found with the OPN expression. The selective distribution of OPN, calcium in the "exocyst" provides a new pathological evidence for the "sub-adventitial cystectomy" we developed. The pericyst of hepatic E. granulosus consists of two detachable layers with different formative mechanisms: the "exocyst" layer directing towards the cyst of parasite was the result of granulomatous reaction; also the results suggest OPN is one regulator in the granulomatous reaction and calcification of "exocyst".

Nitric oxide treatment reduces neo-intimal formation and modulates osteopontin expression in an ex-vivo human model of intimal hyperplasia.

PubMed

Colotti, Chiara; Vittorini, Simona; Ottaviano, Virginia; Maltinti, Maristella; Angeli, Valeria; Del Ry, Silvia; Giannessi, Daniela

2009-05-01

In this study the effects of nitric oxide (NO) on intimal hyperplasia (IH) were evaluated in an ex-vivo model of human saphenous vein (SV). SV segments were cultured in conditions able to reproduce IH (FCS), or in medium alone (RPMI), or in presence of a NO donor (NO). Osteopontin (OPN) and Interleukin (IL)-6 were determined in the medium at different culture times and in the tissue, at the end of experiment. OPN and IL-6 release in medium was increased in FCS with respect to RPMI (OPN: 13.9+/-2.9 vs. 2.3+/-0.8 microg/ml, p=0.0011; IL-6: 304.2+/-64.7 vs. 42.0+/-10.1 ng/ml, p<0.0006) as well as intima thickness, that positively correlated with OPN production (r=0.81). In tissue OPN was higher in FCS (82.0+/-30.3 ng/mg protein) than in RPMI (13.8+/-4.2, p=0.0051) and at baseline (3.7+/-0.7, p=0.018). NO reduces IH progression (25%) and both OPN and IL-6 expression (OPN/GAPDH: undetectable baseline; 0.27+/-0.06 RPMI; 0.89+/-0.28 FCS; 0.09+/-0.05 NO; p=0.026 FCS vs. baseline, p=0.018 vs. RPMI, p=0.005 vs. NO). The beneficial NO effect on IH reduction appears to be mediated by the indirect inhibition of OPN production. NO could modulates the initial inflammatory signals that induces the OPN over-production with the related cascade of events leading to IH.

Correlation between calcification and bone sialoprotein and osteopontin in papillary thyroid carcinoma.

PubMed

Wu, Gang; Guo, Jing-Jing; Ma, Zhen-Yu; Wang, Jie; Zhou, Zhong-Wen; Wang, Yi

2015-01-01

The correlation between calcification and papillary thyroid carcinoma has received increasing attention. We investigated the ability of bone sialoprotein (BSP) and osteopontin (OPN) protein levels to diagnose papillary thyroid carcinoma (PTC), and explored the correlation between BSP and OPN protein levels and calcification in PTC. Archival PTC specimens from patients with PTC with calcification and lateral cervical lymph node metastasis (LNM) were included in this retrospective immunohistochemical study. The protein levels of BSP and OPN were analysed immunohistochemically using routinely prepared tissue sections. PTC specimens from 66 patients with PTC were reviewed retrospectively (25 patients with histological calcification seen in paraffin sections, 41 patients without calcification; 35 patients with lateral cervical LNM, 31 patients without LNM). The percentage of samples that had cells that demonstrated positive protein staining differed significantly between PTC specimens, benign thyroid nodules, and adjacent normal follicular epithelium (BSP: 87.88%, 55.00%, and 42.50%, respectively; OPN: 83.33%, 70.00% and 50.00%, respectively). There was a significant difference in the immunohistochemical score (IHS) for BSP and OPN protein staining between PTC specimens with and without calcification (P < 0.05). The level of BSP protein staining was found to be significantly correlated with the level of OPN protein staining in PTC specimens. We conclude that the strong correlation between BSP and OPN and PTC suggests a role for BSP and OPN in calcification and tumor progression of PTC. BSP and OPN might be useful tumour markers for the diagnosis of PTC with limited value, because both of them had low specificity.

Higher Matrix Stiffness Upregulates Osteopontin Expression in Hepatocellular Carcinoma Cells Mediated by Integrin β1/GSK3β/β-Catenin Signaling Pathway.

PubMed

You, Yang; Zheng, Qiongdan; Dong, Yinying; Wang, Yaohui; Zhang, Lan; Xue, Tongchun; Xie, Xiaoying; Hu, Chao; Wang, Zhiming; Chen, Rongxin; Wang, Yanhong; Cui, Jiefeng; Ren, Zhenggang

2015-01-01

Increased stromal stiffness is associated with hepatocellular carcinoma (HCC) development and progression. However, the molecular mechanism by which matrix stiffness stimuli modulate HCC progress is largely unknown. In this study, we explored whether matrix stiffness-mediated effects on osteopontin (OPN) expression occur in HCC cells. We used a previously reported in vitro culture system with tunable matrix stiffness and found that OPN expression was remarkably upregulated in HCC cells with increasing matrix stiffness. Furthermore, the phosphorylation level of GSK3β and the expression of nuclear β-catenin were also elevated, indicating that GSK3β/β-catenin pathway might be involved in OPN regulation. Knock-down analysis of integrin β1 showed that OPN expression and p-GSK3β level were downregulated in HCC cells grown on high stiffness substrate compared with controls. Simultaneously, inhibition of GSK-3β led to accumulation of β-catenin in the cytoplasm and its enhanced nuclear translocation, further triggered the rescue of OPN expression, suggesting that the integrin β1/GSK-3β/β-catenin pathway is specifically activated for matrix stiffness-mediated OPN upregulation in HCC cells. Tissue microarray analysis confirmed that OPN expression was positively correlated with the expression of LOX and COL1. Taken together, high matrix stiffness upregulated OPN expression in HCC cells via the integrin β1/GSK-3β/β-catenin signaling pathway. It highlights a new insight into a pathway involving physical mechanical signal and biochemical signal molecules which contributes to OPN expression in HCC cells.

Plasma osteopontin levels in patients with head and neck cancer and cervix cancer are critically dependent on the choice of ELISA system.

PubMed

Vordermark, Dirk; Said, Harun M; Katzer, Astrid; Kuhnt, Thomas; Hänsgen, Gabriele; Dunst, Jürgen; Flentje, Michael; Bache, Matthias

2006-08-15

The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma surrogate marker of tumor hypoxia and as an indicator of the presence of pleural mesothelioma in asbestos-exposed individuals. The clinical introduction of plasma OPN measurements requires the availability of a reliable enzyme-linked immunosorbence assay (ELISA). We compared previously described and currently available ELISA systems on 88 archival plasma samples obtained from patients with head and neck or cervix cancer between 20 days before and 171 after the start of radiotherapy. Median (range) plasma OPN levels were 667 (148.8-2095) ng/ml and 9.8 (3.5-189.5) ng/ml for a previously described and a newly marketed assay, respectively. Although results for different assays were significantly correlated (r = 0.38, p < 0.05, Spearman rank test), between-assay factors ranged from 2.0 to 217.9 (median 74.6) in individual patients. OPN levels in cervix cancer patients were comparable to those of head and neck cancer patients. Commercially available OPN ELISA systems produce different absolute plasma OPN levels, compromising a comparison of individual patient data with published results. However, different assays appear to have a similar capacity to rank patients according to plasma OPN level. A review of literature data suggests that plasma OPN levels measured even with identical ELISA systems can only be compared with caution.

Osteopontin-deficient progenitor cells display enhanced differentiation to adipocytes.

PubMed

Moreno-Viedma, Veronica; Tardelli, Matteo; Zeyda, Maximilian; Sibilia, Maria; Burks, J Deborah; Stulnig, Thomas M

2018-03-06

Osteopontin (OPN, Spp1) is a protein upregulated in white adipose tissue (WAT) of obese subjects. Deletion of OPN protects mice from high-fat diet-induced WAT inflammation and insulin resistance. However, the alterations mediated by loss of OPN in WAT before the obesogenic challenge have not yet been investigated. Therefore, we hypothesised that the lack of OPN might enhance the pro-adipogenic micro environment before obesity driven inflammation. OPN deficiency was tested in visceral (V) and subcutaneous (SC) WAT from WT and Spp1 -/- female mice. Gene expression for hypoxia, inflammation and adipogenesis was checked in WT vs. Spp1 -/- mice (n=15). Adipocytes progenitor cells (APC) were isolated by fluorescence cell sorting and role of OPN deficiency in adipogenesis was investigated by cell images and RT-PCR. We show that Spp1 -/- maintained normal body and fat-pad weights, although hypoxia and inflammation markers were significantly reduced. In contrast, expression of genes involved in adipogenesis was increased in WAT from Spp1 -/- mice. Strikingly, APC from Spp1 -/- were diminished but differentiated more efficiently to adipocytes than those from control mice. APC from SC-WAT of lean OPN-deficient mice display an enhanced capacity for differentiating to adipocytes. These alterations may explain the healthy expansion of WAT in the OPN-deficient model which is associated with reduced inflammation and insulin resistance. Copyright © 2018. Published by Elsevier Ltd.

Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling.

PubMed

Li, Yinghua; Xie, Yunpeng; Cui, Dan; Ma, Yanni; Sui, Linlin; Zhu, Chenyang; Kong, Hui; Kong, Ying

2015-01-01

Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8), Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2) and epithelial-mesenchymal transition (EMT)-related factors in HEC-1A cells treated with rhOPN. rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT) and Extracellular regulated protein kinases (ERK1/2) signaling pathway. These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer. © 2015 The Author(s) Published by S. Karger AG, Basel.

Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells.

PubMed

Scutera, Sara; Salvi, Valentina; Lorenzi, Luisa; Piersigilli, Giorgia; Lonardi, Silvia; Alotto, Daniela; Casarin, Stefania; Castagnoli, Carlotta; Dander, Erica; D'Amico, Giovanna; Sozzani, Silvano; Musso, Tiziana

2018-01-01

Mesenchymal stromal cells (MSCs) exert immunosuppressive effects on immune cells including dendritic cells (DCs). However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopontin (OPN), a cytokine involved in homeostatic and pathophysiologic responses, is constitutively expressed by DCs and regulated in the DC/MSC cocultures depending on the activation state of MSCs. Resting MSCs promoted OPN production, whereas the production of OPN was suppressed when MSCs were activated by proinflammatory cytokines (i.e., TNF-α, IL-6, and IL-1β). OPN induction required cell-to-cell contact, mediated at least in part, by β1 integrin (CD29). Conversely, activated MSCs inhibited the release of OPN via the production of soluble factors with a major role played by Prostaglandin E 2 (PGE 2 ). Accordingly, pretreatment with indomethacin significantly abrogated the MSC-mediated suppression of OPN while the direct addition of exogenous PGE 2 inhibited OPN production by DCs. Furthermore, DC-conditioned medium promoted osteogenic differentiation of MSCs with a concomitant inhibition of adipogenesis. These effects were paralleled by the repression of the adipogenic markers PPARγ, adiponectin, and FABP4, and induction of the osteogenic markers alkaline phosphatase, RUNX2, and of the bone-anabolic chemokine CCL5. Notably, blocking OPN activity with RGD peptides or with an antibody against CD29, one of the OPN receptors, prevented the effects of DC-conditioned medium on MSC differentiation and CCL5 induction. Because MSCs have a key role in maintenance of bone marrow (BM) hematopoietic stem cell niche through reciprocal regulation with immune cells, we investigated the possible MSC/DC interaction in human BM by immunohistochemistry. Although DCs (CD1c + ) are a small percentage of BM cells, we demonstrated colocalization of CD271 + MSCs with CD1c + DCs in normal and myelodysplastic BM. OPN reactivity was observed in occasional CD1c + cells in the proximity of CD271 + MSCs. Altogether, these results candidate OPN as a signal modulated by MSCs according to their activation status and involved in DC regulation of MSC differentiation.

Upper Tract Urological Laparoendoscopic Single-Site Surgery (LESS)

PubMed Central

Tugcu, Volkan; Sahin, Selcuk; Seker, Gokhan; Kargi, Taner; Tasci, Ali Ihsan

2015-01-01

Background and Objectives: Our objective is to report intermediate-term outcomes for patients who have undergone upper tract urologic laparoendoscopic single-site surgery (LESS) at a single institution. Methods: From January 1, 2008, through November 30, 2012, 107 cases treated with LESS were identified, including pyeloplasty (n = 30), ureterolithotomy (n = 32), nephrectomy (n = 35; simple = 31, partial = 4), and cyst decortication (n = 10). Perioperative data were reviewed, and conversion and complication rates were noted. Results: The median follow-up was 21.5 months for pyeloplasty, 20.5 for ureterolithotomy, 28.0 for simple nephrectomy, 14.0 for partial nephrectomy, and 19.0 for cyst decortication. Major complications were encountered in 8 patients, including 3 intraoperative complications (2 bowel injury with serosal tearing and 1 intraoperative bleeding), which were recognized and repaired with LESS or conversion to conventional laparoscopy (CL). During the intermediate postoperative period (30–90 days) major complications occurred in 5 patients: 4 ureteral strictures (Clavien-Dindo grade [CG] IIIb) and 1 urinoma formation (CG IIIa). During the early postoperative period (<30 days), the most common minor complications were flank pain (CG I) in 16 patients and urinary tract infection (CG II) in 11, followed by urinary leakage (CG I) in 8. Conclusions: Intermediate-term functional outcomes of this single-center study confirm that upper tract LESS is a challenging procedure that can be safe and effective when performed by an experienced team. Prospective studies with longer follow-up periods are needed to investigate the safety of LESS in the treatment of various upper urinary tract conditions. PMID:26648679

Using a Harmonic Scalpel "Drilling and Clamping" Method to Implement Zero Ischemic Robotic-assisted Partial Nephrectomy: An Observation Case Report Study.

PubMed

Hou, Chen-Pang; Lin, Yu-Hsiang; Hsu, Yu-Chao; Chen, Chien-Lun; Chang, Phei-Lang; Tsui, Ke-Hung

2016-01-01

Robot-assisted partial nephrectomy (RAPN) has gradually become a popular minimally invasive nephron-sparing surgical option for small renal tumors. Ischemic injury should be minimized because it impacts renal function outcomes following partial nephrectomy. Herein, the authors detail the technique and present initial perioperative outcomes of our novel harmonic scalpel "drilling and clamping" method to implement zero-ischemic RAPN. The authors prospectively collected baseline and perioperative data of patients who underwent zero ischemic RAPN performed by our harmonic scalpel "drilling and clamping" method. From April 2012 to December 2014, a total of 19 consecutive zero ischemic RAPN procedures were performed by a single surgeon. For 18 of the 19 patients, RAPN using our harmonic scalpel "Drilling and Clamping" method was successfully completed without the need for hilar clamping. The median tumor size was 3.4 cm (range: 1.8-6.2); operative time was 3.2 hours (range: 1.9-4.5); blood loss was 100 mL (range: 30-950); and postoperative hospital stay was 4 days (3-26). One patient required intraoperative blood transfusion. Two patients had intra or postoperative complications: 1 was converted to traditional laparotomy because of massive bleeding, whereas another had postoperative stress ulcer. Pathology confirmed renal cell carcinoma in 13 patients (63.2%), angiomyolipoma in 6 patients: (31.5%), and oncocytoma in 1 patient (5.3%). Mean pre- and postoperative serum creatinine (0.82 mg/dL and 0.85 mg/dL, respectively), estimated glomerular filtration rate (84.12 and 82.18, respectively), and hemoglobin (13.27 g/dL and 12.71 g/dL, respectively) were comparable. The authors present a novel zero-ischemic technique for RAPN. They believe that this technique is feasible and reproducible.

Do fibrin sealants impact negative outcomes after robot-assisted partial nephrectomy?

PubMed

Cohen, Jason; Jayram, Gautam; Mullins, Jeffrey K; Ball, Mark W; Allaf, Mohamad E

2013-10-01

Contemporary rates of postoperative hemorrhage after partial nephrectomy (PN) are low. Commercially available hemostatic agents are commonly used during this surgery to reduce this risk despite a paucity of data supporting the practice. We assessed the impact of fibrin sealant hemostatic agents, a costly addition to surgeries, during robot-assisted partial nephrectomy (RAPN). Between 2007 and 2011, 114 consecutive patients underwent RAPN by a single surgeon (MEA). Evicel fibrin sealant was used in the first 74 patients during renorraphy. The last 40 patients had renorraphy performed without the use of any hemostatic agents. Clinicopathologic, operative, and complication data were compared between groups. Multivariate and univariate logistic regression analysis was performed to test the association between the use of fibrin sealants and operative outcomes. Patient demographic data and clinical tumor characteristics were similar between groups. The use of fibrin sealant did not increase operative time (166.3 vs 176.1 minutes, P=0.28), warm ischemia time (WIT) (14.4 vs 16.1 minutes, P=0.18), or length of hospital stay (2.6 vs 2.4 days, P=0.35). The omission of these agents did not increase estimated blood loss (116.6 vs 176.1 mL, P=0.8) or postoperative blood transfusion (0% vs 2.5%, P=0.17). Univariate analysis demonstrated no association between use of fibrin sealants and increased complications (P>0.05). Multivariable logistic regression showed no statistically significant predictive value of omission of hemostatic agents for perioperative outcomes (P>0.05). Perioperative hemorrhage and other major complications after contemporary RAPN are rare in experienced hands. In our study, the use of fibrin sealants during RAPN does not decrease the rate of complications, blood loss, or hospital stay. Furthermore, no impact is seen on operative time, WIT, or other negative outcomes. Omitting these agents during RAPN could be a safe, effective, cost-saving measure.

A single overnight stay is possible for most patients undergoing robotic partial nephrectomy.

PubMed

Abaza, Ronney; Shah, Ketul

2013-02-01

To evaluate establishment of overnight stay only as sufficient after robotic partial nephrectomy (RPN). Stated benefits of minimally invasive surgery include reduced hospitalization, but published hospital stays after laparoscopic or robotic partial nephrectomy are not significantly less than with open surgery. We developed a clinical pathway targeting discharge on postoperative day (POD) 1 after RPN of any complexity. We reviewed all RPNs by a single surgeon since instituting our clinical pathway, including ambulation and diet the night of surgery, avoidance of intravenous narcotics and drains, and catheter removal on POD 1 before discharge. Targeted discharge was not modified regardless of RPN complexity. A total of 150 consecutive patients underwent 160 RPNs with 35 hilar tumors and 26 with segmental, and 33 with no artery clamping. Three had solitary kidneys, and 8 underwent multiple (range, 2-4) RPNs. Mean patient age was 57 years (range, 22-89 years), and body mass index was 32 kg/m(2) (range, 18-54 kg/m(2)). Mean tumor size was 3.6 cm (range, 1.0-11.0; median, 3.2 cm), and the RENAL (radius, exophytic/endophytic, nearness to collecting system, anterior/posterior, and location) nephrometry score was 8 (range, 4-12; median, 8). Mean warm ischemia time was 12.1 minutes (range, 0-30.0 minutes). Mean preoperative and discharge creatinine were 0.9 mg/dL (range, 0.43-2.79 mg/dL) and 1.13 mg/dL (range, 0.56-2.93 mg/dL). All patients ambulated on POD 0. One patient required one dose of intravenous narcotic. Mean length of stay was 1.1 days, with 145 (97%) discharged on POD 1, of which only 4 (2.7%) were readmitted within 30 days. Discharge on POD 1 is feasible in most RPN patients regardless of complexity. Readmission rate was low, indicating that longer admissions may not prevent complications when patients meeting discharge criteria go home on POD 1. Copyright © 2013 Elsevier Inc. All rights reserved.

Internal validation of the renal pelvic score: a novel marker of renal pelvic anatomy that predicts urine leak after partial nephrectomy.

PubMed

Tomaszewski, Jeffrey J; Smaldone, Marc C; Cung, Bic; Li, Tianyu; Mehrazin, Reza; Kutikov, Alexander; Canter, Daniel J; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2014-08-01

To internally validate the renal pelvic score (RPS) in an expanded cohort of patients undergoing partial nephrectomy (PN). Our prospective institutional renal cell carcinoma database was used to identify all patients undergoing PN for localized renal cell carcinoma from 2007 to 2013. Patients were classified by RPS as having an intraparenchymal or extraparenchymal renal pelvis. Multivariate logistic regression models were used to examine the relationship between RPS and urine leak. Eight hundred thirty-one patients (median age, 60 ± 11.6 years; 65.1% male) undergoing PN (57.3% robotic) for low (28.9%), intermediate (56.5%), and high complexity (14.5%) localized renal tumors (median size, 3.0 ± 2.3 cm; median nephrometry score, 7.0 ± 2.6) were included. Fifty-four patients (6.5%) developed a clinically significant or radiographically identified urine leak. Seventy-two of 831 renal pelvises (8.7%) were classified as intraparenchymal. Intrarenal pelvic anatomy was associated with a markedly increased risk of urine leak (43.1% vs 3.0%; P <.001), major urine leak requiring intervention (23.6% vs 1.7%; P <.001), and minor urine leak (19.4% vs 1.2%; P <.001) compared with that in patients with an extrarenal pelvis. After multivariate adjustment, RPS (intraparenchymal renal pelvis; odds ratio [OR], 24.8; confidence interval [CI], 11.5-53.4; P <.001) was the most predictive of urine leak as was tumor endophyticity ("E" score of 3 [OR, 4.5; CI, 1.3-15.5; P = .018]), and intraoperative collecting system entry (OR, 6.1; CI, 2.5-14.9; P <.001). Renal pelvic anatomy as measured by the RPS best predicts urine leak after open and robotic partial nephrectomy. Although external validation of the RPS is required, preoperative identification of patients at increased risk for urine leak should be considered in perioperative management and counseling algorithms. Copyright © 2014 Elsevier Inc. All rights reserved.

Biological role of site-specific O-glycosylation in cell adhesion activity and phosphorylation of osteopontin.

PubMed

Oyama, Midori; Kariya, Yoshinobu; Kariya, Yukiko; Matsumoto, Kana; Kanno, Mayumi; Yamaguchi, Yoshiki; Hashimoto, Yasuhiro

2018-05-09

Osteopontin (OPN) is an extracellular glycosylated phosphoprotein that promotes cell adhesion by interacting with several integrin receptors. We previously reported that an OPN mutant lacking five O-glycosylation sites (Thr 134 /Thr 138 /Thr 143 /Thr 147 /Thr 152 ) in the threonine/proline-rich region increased cell adhesion activity and phosphorylation compared with the wild type. However, the role of O-glycosylation in cell adhesion activity and phosphorylation of OPN remains to be clarified. Here, we show that site-specific O-glycosylation in the threonine/proline-rich region of OPN affects its cell adhesion activity and phosphorylation independently and/or synergistically. Using site-directed mutagenesis, we found that OPN mutants with substitution sets of Thr 134 /Thr 138 or Thr 143 /Thr 147 /Thr 152 had decreased and increased cell adhesion activity, respectively. In contrast, the introduction of a single mutation into the O-glycosylation sites had no effect on OPN cell adhesion activity. An adhesion assay using function-blocking antibodies against αvβ3 and β1 integrins, as well as αvβ3 integrin-overexpressing A549 cells, revealed that site-specific O-glycosylation affected the association of OPN with the two integrins. Phosphorylation analyses using phos-tag and LC-MS/MS indicated that phosphorylation levels and sites were influenced by the O-glycosylation status, although the number of O-glycosylation sites was not correlated with the phosphorylation level in OPN. Furthermore, a correlation analysis between phosphorylation level and cell adhesion activity in OPN mutants with the site-specific O-glycosylation showed that they were not always correlated. These results provide conclusive evidence of a novel regulatory mechanism of cell adhesion activity and phosphorylation of OPN by site-specific O-glycosylation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Plasma osteopontin in acute liver failure.

PubMed

Srungaram, Praveen; Rule, Jody A; Yuan, He Jun; Reimold, Andreas; Dahl, Benny; Sanders, Corron; Lee, William M

2015-06-01

Osteopontin (OPN) is a novel phosphoglycoprotein expressed in Kupffer cells that plays a pivotal role in activating natural killer cells, neutrophils and macrophages. Measuring plasma OPN levels in patients with acute liver failure (ALF) might provide insights into OPN function in the setting of massive hepatocyte injury. OPN levels were measured using a Quantikine® ELISA assay on plasma from 105 consecutive ALF patients enrolled by the US Acute Liver Failure Study Group, as well as controls including 40 with rheumatoid arthritis (RA) and 35 healthy subjects both before, and 1 and 3 days after undergoing spine fusion (SF) surgery as a model for acute inflammation. Median plasma OPN levels across all etiologies of ALF patients were elevated 10- to 30-fold: overall median 1055ng/mL; range: 33-19,127), when compared to healthy controls (median in pre-SF patients: 41ng/mL; range 2.6-86.4). RA and SF post op patients had elevated OPN levels (37ng/mL and 198ng/mL respectively), well below those of the ALF patients. Median OPN levels were highest in acetaminophen (3603ng/mL) and ischemia-related ALF (4102ng/mL) as opposed to viral hepatitis (706ng/mL), drug-induced liver injury (353ng/mL) or autoimmune hepatitis (436ng/mL), correlating with the degree of hepatocellular damage, as reflected by aminotransferase values (R value: 0.47 for AST, p<0.001). OPN levels appeared to correlate with degree of liver necrosis in ALF. Very high levels were associated with hyperacute injury and good outcomes. Whether OPN exerts a protective effect in limiting disease progression in this setting remains uncertain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evolution and functional characterisation of melanopsins in a deep-sea chimaera (elephant shark, Callorhinchus milii).

PubMed

Davies, Wayne I L; Tay, Boon-Hui; Zheng, Lei; Danks, Janine A; Brenner, Sydney; Foster, Russell G; Collin, Shaun P; Hankins, Mark W; Venkatesh, Byrappa; Hunt, David M

2012-01-01

Non-visual photoreception in mammals is primarily mediated by two splice variants that derive from a single melanopsin (OPN4M) gene, whose expression is restricted to a subset of retinal ganglion cells. Physiologically, this sensory system regulates the photoentrainment of many biological rhythms, such as sleep via the melatonin endocrine system and pupil constriction. By contrast, melanopsin exists as two distinct lineages in non-mammals, opn4m and opn4x, and is broadly expressed in a wide range of tissue types, including the eye, brain, pineal gland and skin. Despite these findings, the evolution and function of melanopsin in early vertebrates are largely unknown. We, therefore, investigated the complement of opn4 classes present in the genome of a model deep-sea cartilaginous species, the elephant shark (Callorhinchus milii), as a representative vertebrate that resides at the base of the gnathostome (jawed vertebrate) lineage. We reveal that three melanopsin genes, opn4m1, opn4m2 and opn4x, are expressed in multiple tissues of the elephant shark. The two opn4m genes are likely to have arisen as a result of a lineage-specific duplication, whereas "long" and "short" splice variants are generated from a single opn4x gene. By using a heterologous expression system, we suggest that these genes encode functional photopigments that exhibit both "invertebrate-like" bistable and classical "vertebrate-like" monostable biochemical characteristics. We discuss the evolution and function of these melanopsin pigments within the context of the diverse photic and ecological environments inhabited by this chimaerid holocephalan, as well as the origin of non-visual sensory systems in early vertebrates.

Evolution and Functional Characterisation of Melanopsins in a Deep-Sea Chimaera (Elephant Shark, Callorhinchus milii)

PubMed Central

Davies, Wayne I. L.; Tay, Boon-Hui; Zheng, Lei; Danks, Janine A.; Brenner, Sydney; Foster, Russell G.; Collin, Shaun P.; Hankins, Mark W.; Venkatesh, Byrappa; Hunt, David M.

2012-01-01

Non-visual photoreception in mammals is primarily mediated by two splice variants that derive from a single melanopsin (OPN4M) gene, whose expression is restricted to a subset of retinal ganglion cells. Physiologically, this sensory system regulates the photoentrainment of many biological rhythms, such as sleep via the melatonin endocrine system and pupil constriction. By contrast, melanopsin exists as two distinct lineages in non-mammals, opn4m and opn4x, and is broadly expressed in a wide range of tissue types, including the eye, brain, pineal gland and skin. Despite these findings, the evolution and function of melanopsin in early vertebrates are largely unknown. We, therefore, investigated the complement of opn4 classes present in the genome of a model deep-sea cartilaginous species, the elephant shark (Callorhinchus milii), as a representative vertebrate that resides at the base of the gnathostome (jawed vertebrate) lineage. We reveal that three melanopsin genes, opn4m1, opn4m2 and opn4x, are expressed in multiple tissues of the elephant shark. The two opn4m genes are likely to have arisen as a result of a lineage-specific duplication, whereas “long” and “short” splice variants are generated from a single opn4x gene. By using a heterologous expression system, we suggest that these genes encode functional photopigments that exhibit both “invertebrate-like” bistable and classical “vertebrate-like” monostable biochemical characteristics. We discuss the evolution and function of these melanopsin pigments within the context of the diverse photic and ecological environments inhabited by this chimaerid holocephalan, as well as the origin of non-visual sensory systems in early vertebrates. PMID:23251480

Osteopontin contributes to effective neutrophil recruitment, IL-1β production and apoptosis in Aspergillus fumigatus keratitis.

PubMed

Zhao, Guiqiu; Hu, Ming; Li, Cui; Lee, Jieun; Yuan, Kelan; Zhu, Guoqiang; Che, Chengye

2018-04-01

Fungal keratitis is a major cause of corneal ulcers, resulting in significant visual impairment and blindness. A phosphorylated glycoprotein secreted by immunocompetent cells, osteopontin (OPN) mediates cluster formation of the host fungal receptors and enhances the phagocytosis and clearance of pathogenic fungi. However, whether OPN production and function occurs in fungal keratitis is unknown. OPN expression in Aspergillus fumigatus keratitis patient corneas was assessed by quantitative polymerase chain reaction (qRT-PCR) and immunofluorescence. Human neutrophils, THP-1 macrophages and corneal epithelial cells (HCECs) stimulated with A. fumigatus were utilized for in vitro experiments. Mouse models of A. fumigatus keratitis were developed by intrastromal injection for in vivo experiments. Using siRNAs, neutralizing antibodies, recombinant proteins and inhibitors, the production and role of OPN in A. fumigatus infection was assessed by clinical evaluation, qRT-PCR, immunofluorescence, western blotting and bioluminescence image acquisition. We observed increased corneal OPN expression in A. fumigatus keratitis patients and mouse models compared to controls. OPN production in response to A. fumigatus infection was dependent on LOX-1 and Erk1/2. Compared to controls, OPN knockdown impaired proinflammatory cytokine IL-1β production, which was dependent on 4E-BP1. OPN knockdown decreased myeloperoxidase levels, and resulted in decreased neutrophil recruitment, higher fungal load and increased apoptosis in mouse A. fumigatus keratitis. Our results indicate that OPN is a critical component of the antifungal immune response and is essential for effective neutrophil recruitment, inflammatory cytokine production and apoptosis in A. fumigatus keratitis. © 2018 Australasian Society for Immunology Inc.

Trends and perioperative outcomes for laparoscopic and robotic nephrectomy using the National Surgical Quality Improvement Program (NSQIP) database.

PubMed

Liu, Jen-Jane; Leppert, John T; Maxwell, Bryan G; Panousis, Periklis; Chung, Benjamin I

2014-05-01

We sought to examine the trends in perioperative outcomes of kidney cancer surgery stratified by type (radical nephrectomy [RN] vs. partial nephrectomy [PN]) and approach (open vs. minimally invasive). We queried the National Surgical Quality Improvement Program database to identify kidney cancer operations performed from 2005 to 2011. We examined 30-day perioperative outcomes including operative time, transfusion rate, length of stay, major morbidity (cardiovascular, pulmonary, renal, and infectious), and mortality. A total of 2,902 PN and 5,459 RN cases were identified. The use of PN increased over time, accounting for 39% of all nephrectomies in 2011. Minimally invasive approaches also increased over time for both RN and PN. Open surgery was associated with increased length of stay, receipt of transfusion, major complications, and perioperative mortality. Resident involvement and open approach were independent predictors of major complications for both PN and RN. Additionally, the presence of a medical comorbidity was also a risk factor for complications after RN. The overall complication rates decreased for all approaches over the study period. Minimally invasive approaches to kidney cancer renal surgery have increased with favorable outcomes. The safety of open and minimally invasive PN improved significantly over the study period. Although pathologic features cannot be determined from this data set, these data show that complications from renal surgical procedures are decreasing in an era of increasing use. © 2013 Published by Elsevier Inc.

Dynamic Light Scattering Study of Inhibition of Nucleation and Growth of Hydroxyapatite Crystals by Osteopontin

PubMed Central

de Bruyn, John R.; Goiko, Maria; Mozaffari, Maryam; Bator, Daniel; Dauphinee, Ron L.; Liao, Yinyin; Flemming, Roberta L.; Bramble, Michael S.; Hunter, Graeme K.; Goldberg, Harvey A.

2013-01-01

We study the effect of isoforms of osteopontin (OPN) on the nucleation and growth of crystals from a supersaturated solution of calcium and phosphate ions. Dynamic light scattering is used to monitor the size of the precipitating particles and to provide information about their concentration. At the ion concentrations studied, immediate precipitation was observed in control experiments with no osteopontin in the solution, and the size of the precipitating particles increased steadily with time. The precipitate was identified as hydroxyapatite by X-ray diffraction. Addition of native osteopontin (nOPN) extracted from rat bone caused a delay in the onset of precipitation and reduced the number of particles that formed, but the few particles that did form grew to a larger size than in the absence of the protein. Recombinant osteopontin (rOPN), which lacks phosphorylation, caused no delay in initial calcium phosphate precipitation but severely slowed crystal growth, suggesting that rOPN inhibits growth but not nucleation. rOPN treated with protein kinase CK2 to phosphorylate the molecule (p-rOPN) produced an effect similar to that of nOPN, but at higher protein concentrations and to a lesser extent. These results suggest that phosphorylations are critical to OPN’s ability to inhibit nucleation, whereas the growth of the hydroxyapatite crystals is effectively controlled by the highly acidic OPN polypeptide. This work also demonstrates that dynamic light scattering can be a powerful tool for delineating the mechanism of protein modulation of mineral formation. PMID:23457612

Immunolocalization of osteopontin in dysplasias and squamous cell carcinomas arising from oral epithelium.

PubMed

Aravind, Thara; Janardhanan, Mahija; Rakesh, S; Savithri, Vindhya; Unnikrishnan, U G

2017-01-01

Early detection of oral squamous cell carcinoma (OSCC) remains one of the most efficient ways to ensure patient survival and improved quality of life. Although specific biomarkers related to OSCC have been investigated, a useful biomarker that assesses the transition potential of potentially malignant lesion to OSCC remains to be found. Osteopontin (OPN) has been recognized as an important factor in tumorigenesis and their expression in OSCC have been investigated earlier. In the present study, evaluation of OPN expression in premalignant and malignant lesions has been carried out to assess their possible role as a biomarker in the early diagnosis and prognosis of OSCC. The objective of this study is to evaluate the role of OPN as a biomarker in the diagnosis and prognosis of OSCC. The study group consisted of archival paraffin-embedded blocks of ten cases each of varying grades of OSCC, oral epithelial dysplasias and epithelial hyperplasias. Sections were subjected to immunohistochemical staining for the biomarker OPN. A positive OPN expression was noticed in epithelial dysplasias and SCC arising from the oral epithelium. A progressive increase in the intensity of staining was seen with increasing grades of dysplasias and a decrease in OPN expression with an increase in grades was observed in OSCC. The expression of OPN in full thickness of epithelium in severe dysplasias, carcinoma in situ, and in the superficial epithelium of OSCC suggest the possibility of considering OPN expression in full epithelial thickness in dysplasias as an indicator for malignant transformation.

NF-κB– and AP-1–Mediated DNA Looping Regulates Osteopontin Transcription in Endotoxin-Stimulated Murine Macrophages

PubMed Central

Zhao, Wei; Wang, Lijuan; Zhang, Meng; Wang, Peng; Zhang, Lei; Yuan, Chao; Qi, Jianni; Qiao, Yu; Kuo, Paul C.; Gao, Chengjiang

2013-01-01

Osteopontin (OPN) is expressed by various immune cells and modulates both innate and adaptive immune responses. However, the molecular mechanisms that control opn gene expression, especially at the chromatin level, remain largely unknown. We have previously demonstrated many specific cis- and trans-regulatory elements that determine the extent of endotoxin (LPS)-mediated induction of OPN synthesis in murine macrophages. In the present study, we confirm that NF-κB also plays an important role in the setting of LPS-stimulated OPN expression through binding to a distal regulatory element. Importantly, we demonstrate that LPS stimulates chromosomal loops in the OPN promoter between NF-κB binding site and AP-1 binding site using chromosome conformation capture technology. The crucial role of NF-κB and AP-1 in LPS-stimulated DNA looping was confirmed, as small interfering RNA knock-down of NF-κB p65 and AP-1 c-Jun exhibited decreased levels of DNA looping. Furthermore, we demonstrate that p300 can form a complex with NF-κB and AP-1 and is involved in DNA looping and LPS-induced OPN expression. Therefore, we have identified an essential mechanism to remodel the local chromatin structures and spatial conformations to regulate LPS-induced OPN expression. PMID:21257959

Characterization of UO2(2+) binding to osteopontin, a highly phosphorylated protein: insights into potential mechanisms of uranyl accumulation in bones.

PubMed

Qi, Lei; Basset, Christian; Averseng, Olivier; Quéméneur, Eric; Hagège, Agnès; Vidaud, Claude

2014-01-01

Bones are one of the few organs in which uranyl (UO2(2+)) accumulates. This large dioxo-cation displays affinity for carboxylates, phenolates and phosphorylated functional groups in proteins. The noncollagenous protein osteopontin (OPN) plays an important role in bone homeostasis. It is mainly found in the extracellular matrix of mineralized tissues but also in body fluids such as milk, blood and urine. Furthermore, OPN is an intrinsically disordered protein, which, like other proteins of the SIBLING family, contains a polyaspartic acid sequence and numerous patterns of alternating acidic and phosphorylated residues. All these properties led to the hypothesis that this protein could be prone to UO2(2+) binding. In this work, a simple purification procedure enabling highly purified bovine (bOPN) and human OPN (hOPN) to be obtained was developed. Various biophysical approaches were set up to study the impact of phosphorylations on the affinity of OPN for UO2(2+) as well as the formation of stable complexes originating from structural changes induced by the binding of this metal cation. The results obtained suggest a new mechanism of the interaction of UO2(2+) with bone metabolism and a new role for OPN as a metal transporter.

Correlating the nanoscale mechanical and chemical properties of knockout mice bones

NASA Astrophysics Data System (ADS)

Kavukcuoglu, Nadire Beril

Bone is a mineral-organic composite where the organic matrix is mainly type I collagen plus small amounts of non-collagenous proteins including osteopontin (OPN), osteocalcin (OC) and fibrillin 2 (Fbn2). Mature bone undergoes remodeling continually so new bone is formed and old bone resorbed. Uncoupling between the bone resorption and bone formation causes an overall loss of bone mass and leads to diseases like osteoporosis and osteopenia. These are characterized by structural deterioration of the bone tissue and an increased risk of fracture. The non-collagenous bone proteins are known to have a role in regulating bone turnover and to affect the structural integrity of bone. OPN and OC play a key role in bone resorption and formation, while absence of Fbn-2 causes a connective tissue disorder (congenital contractural arachnodactyly) and has been associated with decreased bone mass. In this thesis nanoindentation and Raman-microspectroscopy techniques were used to investigate and correlate the mechanical and chemical properties of cortical femoral bones from OPN deficient (OPN-/-), OC deficient (OC-/-) and Fbn-2 deficient (Fbn2-/-) mice and their age, sex and background matched wild-type controls (OPN+/+, OC+/+ and Fbn2+/+). For OPN the hardness (H) and elastic modulus (E) of under 12 week OPN-/- bones were significantly lower than for OPN+/+ bones, but Raman showed no significant difference. Mechanical properties of bones from mice older than 12 weeks were not significantly different with genotype. However, mineralization and crystallinity from >50 week OPN-/- bones were significantly higher than for OPN+/+ bones. Mechanical properties of OPN-/- bones showed no variation with age, but mineralization, crystallinity and type-B carbonate substitution increased for both genotypes. For OC-/- intra-bone analyses showed that the hardness and crystallinity of the bones were significantly higher, especially in the mid-cortical sections, compared to OC+/+ bones. Fbn2-/- bones had significantly lower hardness and elastic modulus compared to Fbn2+/+ bones, but the crystallinity was higher. Type-B carbonate substitution decreased significantly in OC-/- and Fbn2-/- bones compared to their wild-type controls. The thesis has provided new insight into how non-collagenous proteins affect the nanomechanics and chemistry of bone tissue. This information will assist in the development of new treatments for osteopenia/osteoporosis.

Osteopontin attenuates acute gastrointestinal graft-versus-host disease by preventing apoptosis of intestinal epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawakami, Kentaro; Minami, Naoki; Matsuura, Minoru

Background and aims: Acute graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation, which often targets gastrointestinal (GI) tract. Osteopontin (OPN) plays an important physiological role in the efficient development of Th1 immune responses and cell survival by inhibiting apoptosis. The role of OPN in acute GI-GVHD is poorly understood. In the present study, we investigated the role of OPN in donor T cells in the pathogenicity of acute GI-GVHD. Methods: OPN knockout (KO) mice and C57BL/6 (B6) mice were used as donors, and (C57BL/6 × DBA/2) F1 (BDF1) mice were used as allograft recipients. Mice with acutemore » GI-GVHD were divided into three groups: the control group (BDF1→BDF1), B6 group (B6→BDF1), and OPN-KO group (OPN-KO→BDF1). Bone marrow cells and spleen cells from donors were transplanted to lethally irradiated recipients. Clinical GVHD scores were assessed daily. Recipients were euthanized on day 7 after transplantation, and colons and small intestines were collected for various analyses. Results: The clinical GVHD score in the OPN-KO group was significantly increased compared with the B6 and control groups. We observed a difference in the severity of colonic GVHD between the OPN-KO group and B6 group, but not small intestinal-GVHD between these groups. Interferon-γ, Tumor necrosis factor-α, Interleukin-17A, and Interleukin-18 gene expression in the OPN-KO group was differed between the colon and small intestine. Flow cytometric analysis revealed that the fluorescence intensity of splenic and colonic CD8 T cells expressing Fas Ligand was increased in the OPN-KO group compared with the B6 group. Conclusion: We demonstrated that the importance of OPN in T cells in the onset of acute GI-GVHD involves regulating apoptosis of the intestinal cell via the Fas-Fas Ligand pathway. - Highlights: • A lack of osteopontin in donor cells exacerbated clinical gastrointestinal GVHD. • Donor cells lacking osteopontin affected intestinal inflammation of GVHD. • Donor cells lacking osteopontin increased apoptotic epithelial cells in GVHD. • Osteopontin plays an anti-inflammatory role in acute gastrointestinal GVHD.« less

Adhesion of MC3T3-E1 cells to bone sialoprotein and bone osteopontin specifically bound to collagen I.

PubMed

Bernards, Matthew T; Qin, Chunlin; Ratner, Buddy D; Jiang, Shaoyi

2008-09-01

Bone sialoprotein (BSP) and bone osteopontin (OPN) are members of the SIBLING (small integrin-binding ligand, N-linked glycoproteins) family of proteins commonly found in mineralized tissues. Previously, OPN was shown to exhibit a preferential orientation for MC3T3-E1 cell adhesion when it was specifically bound to collagen. In this work, the orientation of BSP under similar circumstances is examined and compared with OPN. Radiolabeled adsorption isotherms were obtained for BSP bound to both tissue culture polystyrene (TCPS) and collagen-coated TCPS. The results show that collagen has the capacity to bind almost twice as much OPN under identical conditions. An in vitro MC3T3-E1 cell adhesion assay was then performed to compare the cell binding ability of BSP on either TCPS or collagen-coated TCPS with identical amounts of adsorbed protein. It was found that there is no significant difference in the cell binding ability of BSP on either of the substrates. For cell binding studies on collagen-coated TCPS, it was shown that there are a greater number of cells bound to substrates with adsorbed OPN as compared with BSP. The preferable orientation of OPN for cell binding coupled with the higher binding capability of collagen for OPN indicates that OPN is more important than BSP for osteoblast adhesion to the collagen matrix. In addition, a cell inhibition assay was performed to show that all of the cell binding that occurred throughout these studies was dependent upon integrin interactions with the RGD cell binding moiety.

Blocking the expression of both bone sialoprotein (BSP) and osteopontin (OPN) impairs the anabolic action of PTH in mouse calvaria bone.

PubMed

Bouleftour, Wafa; Bouet, Guenaelle; Granito, Renata Neves; Thomas, Mireille; Linossier, Marie-Thérèse; Vanden-Bossche, Arnaud; Aubin, Jane E; Lafage-Proust, Marie-Hélène; Vico, Laurence; Malaval, Luc

2015-03-01

Osteopontin (OPN) and bone sialoprotein (BSP) are coexpressed in osteoblasts and osteoclasts, and display overlapping properties. We used daily injection of parathyroid hormone 1-84 (iPTH) over the calvaria of BSP knockout (-/-) mice to investigate further their functional specificity and redundancy. iPTH stimulated bone formation in both +/+ and -/- mice, increasing to the same degree periosteum, osteoid and total bone thickness. Expression of OPN, osterix, osteocalcin (OCN) and DMP1 was also increased by iPTH in both genotypes. In contrast to +/+, calvaria cell cultures from -/- mice revealed few osteoblast colonies, no mineralization and little expression of OCN, MEPE or DMP1. In contrast, OPN levels were 5× higher in -/- versus +/+ cultures. iPTH increased alkaline phosphatase (ALP) activity in cell cultures of both genotypes, with higher OCN and the induction of mineralization in -/- cultures. siRNA blocking of OPN expression did not alter the anabolic action of the hormone in BSP +/+ calvaria, while it blunted iPTH effects in -/- mice, reduced to a modest increase in periosteum thickness. In -/- (not +/+) cell cultures, siOPN blocked the stimulation by iPTH of ALP activity and OCN expression, as well as the induction of mineralization. Thus, full expression of either OPN or BSP is necessary for the anabolic effect of PTH at least in the ectopic calvaria injection model. This suggests that OPN may compensate for the lack of BSP in the response to this hormonal challenge, and provides evidence of functional overlap between these cognate proteins. © 2014 Wiley Periodicals, Inc., A Wiley Company.

Adhesion of MC3T3-E1 cells to bone sialoprotein and bone osteopontin specifically bound to collagen I

PubMed Central

Bernards, Matthew T.; Qin, Chunlin; Ratner, Buddy D.; Jiang, Shaoyi

2009-01-01

Bone sialoprotein (BSP) and bone osteopontin (OPN) are members of the SIBLING (small integrin-binding ligand, N-linked glycoproteins) family of proteins commonly found in mineralized tissues. Previously, OPN was shown to exhibit a preferential orientation for MC3T3-E1 cell adhesion when it was specifically bound to collagen. In this work, the orientation of BSP under similar circumstances is examined and compared with OPN. Radiolabeled adsorption isotherms were obtained for BSP bound to both tissue culture polystyrene (TCPS) and collagen-coated TCPS. The results show that collagen has the capacity to bind almost twice as much OPN under identical conditions. An in vitro MC3T3-E1 cell adhesion assay was then performed to compare the cell binding ability of BSP on either TCPS or collagen-coated TCPS with identical amounts of adsorbed protein. It was found that there is no significant difference in the cell binding ability of BSP on either of the substrates. For cell binding studies on collagen-coated TCPS, it was shown that there are a greater number of cells bound to substrates with adsorbed OPN as compared with BSP. The preferable orientation of OPN for cell binding coupled with the higher binding capability of collagen for OPN indicates that OPN is more important than BSP for osteoblast adhesion to the collagen matrix. In addition, a cell inhibition assay was performed to show that all of the cell binding that occurred throughout these studies was dependent upon integrin interactions with the RGD cell binding moiety. PMID:18041732

Astaxanthin modulates osteopontin and transforming growth factor β1 expression levels in a rat model of nephrolithiasis: a comparison with citrate administration.

PubMed

Alex, Manju; Sauganth Paul, M V; Abhilash, M; Mathews, Varghese V; Anilkumar, T V; Nair, R Harikumaran

2014-09-01

To evaluate the effect of astaxanthin on renal angiotensin-I converting enzyme (ACE) levels, osteopontin (OPN) and transforming growth factor β1 (TGF-β1) expressions and the extent of crystal deposition in experimentally induced calcium oxalate kidney stone disease in a male Wistar rat model. To compare the efficacy of astaxanthin treatment with a currently used treatment strategy (citrate administration) for kidney stones. The expression of OPN was assessed by immunohistochemistry. One step reverse transcriptase polymerase chain reaction followed by densitometry was used to assess renal OPN and TGF-β1 levels. Renal ACE levels were quantified by an enzyme-linked immunosorbent assay method. Crystal deposition in kidney was analysed by scanning electron microscopic (SEM)-energy-dispersive X-ray (EDX). The renal ACE levels and the expression of OPN and TGF-β1 were upregulated in the nephrolithiasis-induced rats. Astaxanthin treatment reduced renal ACE levels and the expression OPN and TGF-β1. SEM-EDX analysis showed that crystal deposition was reduced in the astaxanthin-treated nephrolithiatic group. Astaxanthin treatment was more effective than citrate administration in the regulation of renal ACE levels, OPN and TGF-β1 expressions. Astaxanthin administration reduced renal calcium oxalate crystal deposition possibly by modulating the renal renin-angiotensin system (RAS), which reduced the expression of OPN and TGF-β1 levels. Astaxanthin administration was more effective than citrate treatment in reducing crystal deposition and down-regulating the expression of OPN and TGF-β1. © 2013 The Authors. BJU International © 2013 BJU International.

Immunolocalization of osteopontin in dysplasias and squamous cell carcinomas arising from oral epithelium

PubMed Central

Aravind, Thara; Janardhanan, Mahija; Rakesh, S; Savithri, Vindhya; Unnikrishnan, U G

2017-01-01

Background: Early detection of oral squamous cell carcinoma (OSCC) remains one of the most efficient ways to ensure patient survival and improved quality of life. Although specific biomarkers related to OSCC have been investigated, a useful biomarker that assesses the transition potential of potentially malignant lesion to OSCC remains to be found. Osteopontin (OPN) has been recognized as an important factor in tumorigenesis and their expression in OSCC have been investigated earlier. In the present study, evaluation of OPN expression in premalignant and malignant lesions has been carried out to assess their possible role as a biomarker in the early diagnosis and prognosis of OSCC. Objectives: The objective of this study is to evaluate the role of OPN as a biomarker in the diagnosis and prognosis of OSCC. Materials and Methods: The study group consisted of archival paraffin-embedded blocks of ten cases each of varying grades of OSCC, oral epithelial dysplasias and epithelial hyperplasias. Sections were subjected to immunohistochemical staining for the biomarker OPN. Results: A positive OPN expression was noticed in epithelial dysplasias and SCC arising from the oral epithelium. A progressive increase in the intensity of staining was seen with increasing grades of dysplasias and a decrease in OPN expression with an increase in grades was observed in OSCC. Conclusion: The expression of OPN in full thickness of epithelium in severe dysplasias, carcinoma in situ, and in the superficial epithelium of OSCC suggest the possibility of considering OPN expression in full epithelial thickness in dysplasias as an indicator for malignant transformation. PMID:28479681

α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression.

PubMed

Jang, Min A; Lee, Seung Jin; Baek, Seung Eun; Park, So Youn; Choi, Young Whan; Kim, Chi Dae

2017-01-01

α-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in Schisandra chinensis (SC), a well-known medicinal herb that ameliorates cardiovascular symptoms. Thus, we examined the effect of ICB on vascular smooth muscle cell (VSMC) proliferation, a key feature of diverse vascular diseases. When VSMCs primary cultured from rat thoracic aorta were stimulated with PDGF (1-10 ng/ml), cell proliferation and osteopontin (OPN) expression were concomitantly up-regulated, but these effects were attenuated when cells were treated with MPIIIB10, a neutralizing monoclonal antibody for OPN. In aortic tissues exposed to PDGF, sprouting VSMC numbers increased, which was attenuated in tissues from OPN-deficient mice. Furthermore, VSMC proliferation and OPN expression induced by PDGF were attenuated dose-dependently by ICB (10 or 30 μg/ml). Reporter assays conducted using OPN promoter-luciferase constructs showed that the promoter region 538-234 bp of the transcription start site was responsible for transcriptional activity enhancement by PDGF, which was significantly inhibited by ICB. Putative binding sites for AP-1 and C/EBPβ in the indicated promoter region were suggested by TF Search, and increased binding of AP-1 and C/EBPβ in PDGF-treated VSMCs was demonstrated using a ChIP assay. The increased bindings of AP-1 and C/EBPβ into OPN promoter were attenuated by ICB. Moreover, the PDGF-induced expression of OPN was markedly attenuated in VSMCs transfected with siRNA for AP-1 and C/EBPβ. These results indicate that ICB inhibit VSMC proliferation by inhibiting the AP-1 and C/EBPβ signaling pathways and thus downregulating OPN expression.

Osteopontin, asbestos exposure and pleural plaques: a cross-sectional study

PubMed Central

2011-01-01

Background Osteopontin (OPN) is a plasma protein/cytokine produced in excess in several malignancies. In a recent study OPN was reported as being related to the duration of asbestos exposure and presence of benign asbestos-related diseases; however, it was unclear whether this protein was an indicator of exposure or effect. Methods In 193 workers, 50 with pleural plaques (PP), in whom different indicators of past asbestos exposure were estimated, OPN plasma levels were assessed using commercial quantitative sandwich enzyme immunoassays according to the manufacturer's instructions. Results Osteopontin increased with increasing age and several aspects of asbestos exposure, without differences related to the presence of pleural plaques. At multivariable regression analysis, the explanatory variables with a significant independent influence on OPN were length of exposure (positive correlation) and time elapsed since last exposure (positive correlation). Conclusions Since asbestos in lung tissue tends to wane over time, OPN should decrease (rather than increase) with time since last exposure. Therefore, OPN cannot be a reliable biomarker of exposure nor effect (presence of pleural plaques). PMID:21477289

A difficult decision: what should we do when malignant tumours are diagnosed in patients supported by left ventricular assist devices?

PubMed

Smail, Hassiba; Pfister, Christian; Baste, Jean-Marc; Nafeh-Bizet, Catherine; Gay, Arnaud; Barbay, Virginie; Bessou, Jean-Paul; Peillon, Christophe; Litzler, Pierre-Yves

2015-09-01

Left ventricular assist devices (LVADs) are used as a bridge to heart transplantation. During the preimplantation or pretransplantation screening, malignant tumours can be discovered. Owing to the lack of guidelines, the management is difficult. We describe our perioperative approach and the patients' outcomes. Between 2006 and 2014, 55 patients underwent implantation of HeartMate II LVAD. Five were diagnosed with malignant tumours: 2 renal, 2 lung and 1 breast tumours. The renal tumours were diagnosed during the preimplantation screening. An LVAD was implanted in both followed by partial nephrectomies 8 and 9 months later. The lung cancers were diagnosed after device implantation, a left pulmonary segmentectomy and a right upper sleeve lobectomy were performed. The breast cancer was diagnosed few months after support and a tumourectomy with lymphadenectomy was performed. Tumour resection was performed successfully in all patients. Prior to surgery haemostasis, device and heart function were evaluated. During surgery, haemodynamics and anticoagulation were monitored. Reoperations were necessary to evacuate haemothorax after lobectomy and an abdominal haematoma post-nephrectomy. After discussion with oncologists, 3 patients were relisted for heart transplantation. Two were successfully transplanted 2 and 3 years after partial nephrectomy with an actual survival of 56 and 59 months after the cancer diagnosis. The follow-up revealed no cancer recurrences. Malignant tumours during support with LVAD can be successfully resected. A multidisciplinary evaluation in these high-risk patients is mandatory. After careful evaluation, regaining the patient's heart transplant candidacy is possible. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Variability of inter-observer agreement on feasibility of partial nephrectomy before and after neoadjuvant axitinib for locally advanced renal cell carcinoma (RCC): independent analysis from a phase II trial.

PubMed

Karam, Jose A; Devine, Catherine E; Fellman, Bryan M; Urbauer, Diana L; Abel, E Jason; Allaf, Mohamad E; Bex, Axel; Lane, Brian R; Thompson, R Houston; Wood, Christopher G

2016-04-01

To evaluate how many patients could have undergone partial nephrectomy (PN) rather than radical nephrectomy (RN) before and after neoadjuvant axitinib therapy, as assessed by five independent urological oncologists, and to study the variability of inter-observer agreement. Pre- and post-systemic treatment computed tomography scans from 22 patients with clear cell renal cell carcinoma in a phase II neoadjuvant axitinib trial were reviewed by five independent urological oncologists. R.E.N.A.L. nephrometry score and κ statistics were calculated. The median R.E.N.A.L. nephrometry score changed from 11 before treatment to 10 after treatment (P = 0.002). Five tumours with moderate complexity before axitinib treatment remained moderate complexity after treatment. Of 17 tumours with high complexity before axitinib treatment, three became moderate complexity after treatment. The overall κ statistic was 0.611. Moderate-complexity κ was 0.611 vs a high-complexity κ of 0.428. Before axitinib treatment the κ was 0.550 vs 0.609 after treatment. After treatment with axitinib, all five reviewers agreed that only five patients required RN (instead of eight before treatment) and that 10 patients could now undergo PN (instead of three before treatment). The odds of PN feasibility were 22.8-times higher after treatment with axitinib. There is considerable variability in inter-observer agreement on the feasibility of PN in patients treated with neoadjuvant targeted therapy. Although more patients were candidates for PN after neoadjuvant axitinib therapy, it remains difficult to identify these patients a priori. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

'Trifecta' outcomes of robot-assisted partial nephrectomy in solitary kidney: a Vattikuti Collective Quality Initiative (VCQI) database analysis.

PubMed

Arora, Sohrab; Abaza, Ronney; Adshead, James M; Ahlawat, Rajesh K; Challacombe, Benjamin J; Dasgupta, Prokar; Gandaglia, Giorgio; Moon, Daniel A; Yuvaraja, Thyavihally B; Capitanio, Umberto; Larcher, Alessandro; Porpiglia, Francesco; Porter, James R; Mottrie, Alexander; Bhandari, Mahendra; Rogers, Craig

2018-01-01

To analyse the outcomes of robot-assisted partial nephrectomy (RAPN) in patients with a solitary kidney in a large multi-institutional database. In all, 2755 patients in the Vattikuti Collective Quality Initiative database underwent RAPN by 22 surgeons at 14 centres in nine countries. Of these patients, 74 underwent RAPN with a solitary kidney between 2007 and 2016. We retrospectively analysed the functional and oncological outcomes of these 74 patients. A 'trifecta' of outcomes was assessed, with trifecta defined as a warm ischaemia time (WIT) of <20 min, negative surgical margins, and no complications intraoperatively or within 3 months of RAPN. All 74 patients underwent RAPN successfully with one conversion to radical nephrectomy. The median (interquartile range [IQR]) operative time was 180 (142-230) min. Early unclamping was used in 11 (14.9%) patients and zero ischaemia was used in 12 (16.2%). Trifecta outcomes were achieved in 38 of 66 patients (57.6%). The median (IQR) WIT was 15.5 (8.75-20.0) min for the entire cohort. The overall complication rate was 24.1% and the rate of Clavien-Dindo grade ≤II complications was 16.3%. Positive surgical margins were present in four cases (5.4%). The median (IQR) follow-up was 10.5 (2.12-24.0) months. The median drop in estimated glomerular filtration rate at 3 months was 7.0 mL/min/1.72 m 2 (11.01%). Our findings suggest that RAPN is a safe and effective treatment option for select renal tumours in solitary kidneys in terms of a trifecta of negative surgical margins, WIT of <20 min, and low operative and perioperative morbidity. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Intraoperative Conversion From Partial to Radical Nephrectomy: Incidence, Predictive Factors, and Outcomes.

PubMed

Petros, Firas G; Keskin, Sarp K; Yu, Kai-Jie; Li, Roger; Metcalfe, Michael J; Fellman, Bryan M; Chang, Courtney M; Gu, Cindy; Tamboli, Pheroze; Matin, Surena F; Karam, Jose A; Wood, Christopher G

2018-06-01

To evaluate preoperative and intraoperative predictors of conversion to radical nephrectomy (RN) in a cohort of patients undergoing a planned partial nephrectomy (PN) for renal cell carcinoma (RCC). A single-center, retrospective review was conducted using our PN database that includes patients who were scheduled to undergo PN (regardless of the approach) but were converted to RN between August 1990 and December 2016. Reasons for conversion were collected from the operative report. Patient demographics and perioperative variables were compared with the successful PN group. Univariate and multivariate logistic regression analyses were conducted to assess predictors of conversion. A total of 1857 patients were scheduled to undergo PN. Of these patients, 90 (5%) were converted to RN. The multivariate model showed that larger tumor size (odds ratio [OR] = 1.20, P = .040), higher RENAL nephrometry score (OR = 1.41, P = .001), hilar tumor or renal sinus invasion (OR = 2.80, P = .004), laparoscopic PN (OR = 7.34, P <.001), intraoperative bleeding (OR = 19.62, P <.001), positive surgical margin (OR = 31.85, P <.001), and advanced pathologic tumor-stage (T3 or T4) (OR = 7.29, P <.001) were associated with increased odds of intraoperative conversion to RN. The rate of conversion to RN was low in patients who were scheduled to undergo PN in this series. Larger tumor size with increasing complexity, hilar tumor location or renal sinus invasion, locally advanced tumors, laparoscopic PN but not robotic PN, bleeding complication, and positive surgical margin were associated with intraoperative conversion from scheduled PN to RN. Copyright © 2018 Elsevier Inc. All rights reserved.

Can a Modified Bosniak Classification System Risk Stratify Pediatric Cystic Renal Masses?

PubMed

Saltzman, Amanda F; Carrasco, Alonso; Colvin, Alexandra N; Meyers, Mariana L; Cost, Nicholas G

2018-03-20

We characterize and apply the modified Bosniak classification system to a cohort of children with cystic renal lesions and known surgical pathology. We identified all patients at our institution with cystic renal masses who also underwent surgery for these lesions. Patients without available preoperative imaging or pathology were excluded. All radiological imaging was independently reviewed by a pediatric radiologist blinded to pathological findings. Imaging characteristics (size, border, septations, calcifications, solid components, vascularity) were recorded from the most recent preoperative ultrasounds and computerized tomograms. The modified Bosniak classification system was applied to these scans and then correlated with final pathology. A total of 22 patients met study criteria. Median age at surgery was 6.1 years (range 11 months to 16.8 years). Of the patients 12 (54.5%) underwent open nephrectomy, 6 (27.3%) open partial nephrectomy, 2 (9.1%) laparoscopic cyst decortication, 1 (4.5%) open renal biopsy and 1 (4.5%) laparoscopic partial nephrectomy. Final pathology was benign in 9 cases (41%), intermediate in 6 (27%) and malignant in 7 (32%). All malignant lesions were modified Bosniak class 4, all intermediate lesions were modified class 3 or 4 and 8 of 9 benign lesions (89%) were modified class 1 or 2. Cystic renal lesions in children with a modified Bosniak class of 1 or 2 were most often benign, while class 3 or 4 lesions warranted surgical excision since more than 90% of masses harbored intermediate or malignant pathology. The modified Bosniak classification system appears to allow for a reasonable clinical risk stratification of pediatric cystic renal masses. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1alpha-related markers, and hemoglobin levels.

PubMed

Bache, Matthias; Reddemann, Rolf; Said, Harun M; Holzhausen, Hans-Jürgen; Taubert, Helge; Becker, Axel; Kuhnt, Thomas; Hänsgen, Gabriele; Dunst, Jürgen; Vordermark, Dirk

2006-12-01

The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO(2)), the hypoxia-related markers hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1alpha, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO(2)), HIF-1alpha and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1alpha expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO(2) correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1alpha or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1alpha, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.

Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: Prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1{alpha}-related markers, and hemoglobin levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bache, Matthias; Reddemann, Rolf; Institute of Pathology, Martin-Luther-University Halle-Wittenberg, Halle

2006-12-01

Purpose: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO{sub 2}), the hypoxia-related markers hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Methods and Materials: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1{alpha}, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO{sub 2}), HIF-1{alpha}more » and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Results: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1{alpha} expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO{sub 2} correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1{alpha} or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Conclusion: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1{alpha}, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.« less

[ORMDL3 polymorphisms and their relationship with OPN and TGF-β1 levels in children with asthma in Hunan, China: an analysis of 98 cases].

PubMed

Yang, Ai-Mei; Huang, Rong; Jin, Shi-Jie

2016-04-01

To investigate ORMDL3 polymorphisms in children with asthma in Hunan, China, and to determine the relationship between ORMDL3 polymorphisms and serum osteopontin (OPN) and transforming growth factor-β1 (TGF-β1) levels. Peripheral blood samples were collected in children with asthma (n=98; astma group) or without asthma (n=30; control group) from Hunan, China. The asthma group was subdivided into atopic (n=62) and non-atopic (n=36) subgroups. Single nucleotide polymorphism (SNP) analysis was performed, and serum OPN and TGF-β1 levels were measured. There were no significant differences in genotype and allele frequencies of rs7216389 of the ORMDL3 gene between the asthma and control groups. The serum level of OPN in the asthma group was significantly higher than in the control group (P<0.05). Both the atopic and non-atopic subgroups showed increased serum levels of OPN compared with the control group (P<0.05). The serum level of TGF-β1 in the atopic subgroup was significantly higher than in the control group (P<0.05). The serum levels of OPN and TGF-β1 showed no significant differences in asthmatic children with different genotypes. The serum levels of OPN and TGF-β1 were in a positive linear correlation in the asthma group (r=0.620; P<0.01) and its two subgroups (r=0.734, 0.649 respectively; P<0.01). In children from Hunan, China, the SNP (rs7216389) of ORMDL3 is not related to asthma susceptibility. OPN and TGF-β1 may be involved in the development of asthma, and they are in a positive linear correlation. The SNP (rs7216389) of ORMDL3 does not influence the expression of OPN and TGF-β1, suggesting that it may not be associated with airway remodeling.

The Monocyte Chemotactic Protein-1 — Interleukin-6 — Osteopontin Pathway of Intra-Aneurysmal Tissue Healing

PubMed Central

Hosaka, Koji; Rojas, Kelley; Fazal, Hanain Z; Schneider, Matheus B; Shores, Jorma; Federico, Vincent; McCord, Matthew; Lin, Li; Hoh, Brian

2017-01-01

Background and Purpose We have previously demonstrated that the local delivery of monocyte chemotactic protein-1 (MCP-1) via a MCP-1-releasing poly(lactic-co-glycolic acid) (PLGA) -coated coil promotes intra-aneurysmal tissue healing. In this study, we demonstrate that interleukin-6 (IL-6) and osteopontin (OPN) are downstream mediators in the MCP-1-mediated aneurysm healing pathway. Methods Murine carotid aneurysms were created in C57BL/6 mice. Drug-releasing coils (MCP-1, IL-6 and OPN) and control PLGA coils were created and then implanted into the aneurysms in order to evaluate their intra-aneurysmal healing capacity. In order to investigate the downstream mediators for aneurysm healing, blocking antibodies for IL-6 receptor and OPN were given to the mice implanted with the MCP-1-releasing coils. A histological analysis of both murine and human aneurysms was utilized to cross-validate the data. Results We observed increased expression of IL-6 in MCP-1-coil treated aneurysms and not in control-PLGA-only treated aneurysms. MCP-1-mediated intra-aneurysmal healing is inhibited in mice given blocking antibody to IL-6 receptor. MCP-1-mediated intra-aneurysmal healing is also inhibited by blocking antibody to OPN. The role of IL-6 in intra-aneurysmal healing is in recruiting of endothelial cells and fibroblasts. Local delivery of OPN to murine carotid aneurysms via OPN-releasing coil significantly promotes intra-aneurysmal healing, but IL-6-releasing coil does not, suggesting that IL-6 cannot promote aneurysm healing independent of MCP-1. In the MCP-1-mediated aneurysm healing, OPN expression is dependent on IL-6; inhibition of IL-6 receptor significantly inhibits OPN expression in MCP-1-mediated aneurysm healing. Conclusions Our findings suggest that IL-6 and OPN are key downstream mediators of MCP-1-mediated intra-aneurysmal healing. PMID:28292871

Intraoperative laparoscopic complications for urological cancer procedures.

PubMed

Montes, Sergio Fernández-Pello; Rodríguez, Ivan Gonzalez; Ugarteburu, Rodrigo Gil; Villamil, Luis Rodríguez; Mendez, Begoña Diaz; Gil, Patricio Suarez; Madera, Javier Mosquera

2015-05-16

To structure the rate of intraoperative complications that requires an intraoperative or perioperative resolution. We perform a literature review of Medline database. The research was focused on intraoperative laparoscopic procedures inside the field of urological oncology. General rate of perioperative complications in laparoscopic urologic surgery is described to be around 12.4%. Most of the manuscripts published do not make differences between pure intraoperative, intraoperative with postoperative consequences and postoperative complications. We expose a narrative statement of complications, possible solutions and possible preventions for most frequent retroperitoneal and pelvic laparoscopic surgery. We expose the results with the following order: retroperitoneal laparoscopic surgery (radical nephrectomy, partial nephrectomy, nephroureterectomy and adrenalectomy) and pelvic laparoscopic surgery (radical prostatectomy and radical cystectomy). Intraoperative complications vary from different series. More scheduled reports should be done in order to better understand the real rates of complications.

Osteoprotective effects of osthole in a mouse model of 5/6 nephrectomy through inhibiting osteoclast formation.

PubMed

Li, Xiaofeng; Xue, Chunchun; Wang, Libo; Tang, Dezhi; Huang, Jian; Zhao, Yongjian; Chen, Yan; Zhao, Dongfeng; Shi, Qi; Wang, Yongjun; Shu, Bing

2016-10-01

The present study aimed to investigate the effects of osthole on osteoclast formation and bone loss in a mouse model of 5/6 nephrectomy. The mice in control and osthole groups were treated 1 month following 5/6 nephrectomy with either a placebo or osthole, respectively. At 2 months post‑nephrectomy, the L4 vertebrae were harvested. The bone mineral density (BMD) of cancellous bone was measured using micro‑CT and tartrate‑resistant acid phosphatase (TRAP) staining was performed to evaluate osteoclast formation. Immunohistochemistry staining and reverse transcription‑quantitative polymerase chain reaction were performed to detect the expression of nuclear factor of activated T‑cells, cytoplasmic‑1 (NFATc‑1), c‑Fos, cathepsin K, Trap, matrix metalloproteinase 9 (Mmp9), osteoprotegerin (Opg) and receptor activator for nuclear factor‑κB ligand (Rankl). Bone marrow cells were cultured with osthole, and osteoclast formation was shown by TRAP staining. Primary calvaria osteoblasts were cultured with osthole, and expression levels of Opg and Rankl were detected. Compared with the sham group, the BMD of mice in model group was significantly reduced. The numbers of osteoclasts and the expression levels of NFATc‑1, c‑Fos, cathepsin K and Mmp9 were significantly increased. Compared with the control group, the mice in the osthole group exhibited increased BMD of the L4 vertebrae, a reduction in osteoclast numbers and decreased expression levels of NFATc‑1, c‑Fos, cathepsin K and Mmp9. In vitro experiments also showed that osteoclast formation was decreased following treatment with osthole. Osteoprotegerin (Opg)/receptor activator for nuclear factor‑κB ligand (Rankl) was upregulated by osthole treatment in the L4 vertebrae and in primary cultures of calvarial osteoblasts. Osthole inhibited osteoclast formation and partially reversed the bone loss induced by 5/6 nephrectomy in mice through the upregulation of OPG/RANKL.

Bone sialoprotein, but not osteopontin, deficiency impairs the mineralization of regenerating bone during cortical defect healing.

PubMed

Monfoulet, Laurent; Malaval, Luc; Aubin, Jane E; Rittling, Susan R; Gadeau, Alain P; Fricain, Jean-Christophe; Chassande, Olivier

2010-02-01

Bone healing is a complex multi-step process, which depends on the position and size of the lesion, and on the mechanical stability of the wounded area. To address more specifically the mechanisms involved in cortical bone healing, we created drill-hole defects in the cortex of mouse femur, a lesion that triggers intramembranous repair, and compared the roles of bone sialoprotein (BSP) and osteopontin (OPN), two proteins of the extracellular matrix, in the repair process. Bone regeneration was analyzed by ex vivo microcomputerized X-ray tomography and histomorphometry of bones of BSP-deficient, OPN-deficient and wild-type mice. In all mouse strains, the cortical gap was bridged with woven bone within 2 weeks and no mineralized tissue was observed in the marrow. Within 3 weeks, lamellar cortical bone filled the gap. The amount and degree of mineralization of the woven bone was not affected by OPN deficiency, but cortical bone healing was delayed in BSP-deficient mice due to delayed mineralization. Gene expression studies showed a higher amount of BSP transcripts in the repair bone of OPN-deficient mice, suggesting a possible compensation of OPN function by BSP in OPN-null mice. Our data suggest that BSP, but not OPN, plays a role in primary bone formation and mineralization of newly formed bone during the process of cortical bone healing. (c) 2009 Elsevier Inc. All rights reserved.

Melanopsin and the Non-visual Photochemistry in the Inner Retina of Vertebrates.

PubMed

Díaz, Nicolás M; Morera, Luis P; Guido, Mario E

2016-01-01

Melanopsin (Opn4), a member of the G-protein-coupled receptor family, is a vitamin A-based opsin in the vertebrate retina that has been shown to be involved in the synchronization of circadian rhythms, pupillary light reflexes, melatonin suppression and other light-regulated tasks. In nonmammalian vertebrates there are two Opn4 genes, Opn4m and Opn4x, the mammalian and Xenopus orthologs respectively. Opn4x is only expressed in nonmammalian vertebrates including reptiles, fish and birds, while Opn4m is found in a subset of retinal ganglion cells (RGCs), the intrinsically photosensitive (ip) RGCs of the inner retina of both mammals and nonmammalian vertebrates. All opsins described utilize retinaldehyde as chromophore, photoisomerized from 11-cis- to all-trans-retinal upon light exposure. Visual retinal photoreceptor cones and rods, responsible for day and night vision respectively, recycle retinoids through a process called the visual cycle that involves the retinal pigment epithelium or glial Müller cells. Although Opn4 has been characterized as a bistable photopigment, little is known about the mechanism/s involved in its chromophore regeneration. In this review, we will attempt to shed light on the visual cycle taking place in the inner retina and discuss the state of the art in the nonvisual photochemistry of vertebrates. © 2015 The American Society of Photobiology.

Partial nephrectomy for renal tumors: lack of correlation between margin status and local recurrence.

PubMed

Antic, Tatjana; Taxy, Jerome B

2015-05-01

To evaluate the relationship between a positive resection margin in partial nephrectomy (PN) and local recurrence. From January 2005 through December 2012, there were 473 PNs in 466 patients at the University of Chicago. A positive margin was defined as tumor extending to the inked specimen edge, either the parenchymal interface or the peripheral fibroadipose tissue. A local recurrence was defined as an ipsilateral tumor of identical histologic type. Renal cell carcinoma (RCC) accounted for 406 tumors: 243 clear cell RCCs (CRCCs), 77 papillary RCCs (PRCCs), and 47 chromophobe RCCs (CHRCCs). Sixty-one RCCs had positive margins: 43 CRCCs, six PRCCs, nine CHRCCs, and three miscellaneous cell types. Of the 61 positive margins, four CRCCs (all originally multifocal) had a local recurrence, two of which occurred in the same patient. One translocation RCC also recurred. Six cases with negative resection margins had a recurrence. A literature review of 3,803 cases, including our study, shows positive margins in 173, of which 13 recurred; however, 39 with negative margins also recurred. A positive margin in PN seldom correlates with a local recurrence. However, protection from recurrence is not ensured by a negative margin. Copyright© by the American Society for Clinical Pathology.

[Hybrid operating room: For what?

PubMed

Benoit, M; Bouvier, A; Bigot, P

2017-11-01

Hybrid operating rooms (HOR) are rooms that mix interventional radiology and surgical equipments. They are usually used in heart, vascular, orthopedic and neurosurgery, and make it possible to consider new minimally invasive procedures in urology. Thanks to these, we developed a new partial nephrectomy technique without renal pedicle clamping and without ischemia. Renal cancer is now diagnosed at localized stage in most of the cases, and its treatment is mostly based on nephron sparing surgery. However, the hemorrhagic character of this intervention requires a renal pedicle clamping whose long-term consequences on renal function are discussed. It also exposes to a classical complication: the renal artery pseudoaneurysm. Therefore, we developed a new laparoscopic partial nephrectomy technique without clamping or approach of renal pedicle, by a selective embolization of tumor vessels through an endovascular route, immediately before the surgery. HOR allowed the combination of the two procedures in the same time and space unit. Tumor staining by Bleu Patenté also aids the surgeon in its spotting. HOR allow a new approach in localized renal cancer management, and should be used in many other urologic surgeries in years to come. They represent a technological advancement by combining interventional radiologists and surgeons' expertise. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

MC3T3-E1 cell adhesion to hydroxyapatite with adsorbed bone sialoprotein, bone osteopontin, and bovine serum albumin.

PubMed

Bernards, Matthew T; Qin, Chunlin; Jiang, Shaoyi

2008-07-15

Native bone tissue is composed of a complex matrix of collagen, non-collagenous proteins, and hydroxyapatite (HAP). Bone sialoprotein (BSP) and bone osteopontin (OPN) are members of the non-collagenous protein family termed the SIBLING (small integrin-binding ligand, N-linked glycoproteins) proteins, which are primarily found in mineralized tissues. Previously, OPN was shown to exhibit a preferential orientation for MC3T3-E1 cell adhesion when it was specifically bound to collagen, while the MC3T3-E1 cell adhesion was shown to be dependant on the conformational flexibility of BSP specifically bound to collagen. Additionally, OPN was shown to play a greater role than BSP for cell binding to collagen. In this work, the orientations and conformations of BSP and OPN specifically bound to HAP are probed under similar conditions. Radiolabeled adsorption isotherms were obtained for BSP and OPN on HAP formed from a simulated body fluid, and the results show that HAP has the capacity to bind significantly more BSP than OPN. An in vitro MC3T3-E1 cell adhesion assay was then performed to compare the cell binding ability of adsorbed BSP and OPN specifically bound to HAP. It was found that there is a preference for cell binding to HAP with adsorbed BSP as compared to OPN, but not to a statistically significant level. However, the maximum cell binding was observed on HAP substrates with adsorbed heat denatured bovine serum albumin (BSA). The influence of BSA on cell binding was shown to be concentration dependant and it is believed that the adsorbed BSA modulates the proliferation state of the bound cells.

MC3T3-E1 Cell Adhesion to Hydroxyapatite with Adsorbed Bone Sialoprotein, Bone Osteopontin, and Bovine Serum Albumin

PubMed Central

Bernards, Matthew T.; Qin, Chunlin; Jiang, Shaoyi

2008-01-01

Native bone tissue is composed of a complex matrix of collagen, non-collagenous proteins, and hydroxyapatite (HAP). Bone sialoprotein (BSP) and bone osteopontin (OPN) are members of the non-collagenous protein family termed the SIBLING (small integrin-binding ligand, N-linked glycoproteins) proteins, which are primarily found in mineralized tissues. Previously, OPN was shown to exhibit a preferential orientation for MC3T3-E1 cell adhesion when it was specifically bound to collagen, while the MC3T3-E1 cell adhesion was shown to be dependant on the conformational flexibility of BSP specifically bound to collagen. Additionally, OPN was shown to play a greater role than BSP for cell binding to collagen. In this work, the orientations and conformations of BSP and OPN specifically bound to HAP are probed under similar conditions. Radiolabeled adsorption isotherms were obtained for BSP and OPN on HAP formed from a simulated body fluid, and the results show that HAP has the capacity to bind significantly more BSP than OPN. An in vitro MC3T3-E1 cell adhesion assay was then performed to compare the cell binding ability of adsorbed BSP and OPN specifically bound to HAP. It was found that there is a preference for cell binding to HAP with adsorbed BSP as compared to OPN, but not to a statistically significant level. However, the maximum cell binding was observed on HAP substrates with adsorbed heat denatured bovine serum albumin (BSA). The influence of BSA on cell binding was shown to be concentration dependant and it is believed that the adsorbed BSA modulates the proliferation state of the bound cells. PMID:18420388

Plumbagin reduces osteopontin-induced invasion through inhibiting the Rho-associated kinase signaling pathway in A549 cells and suppresses osteopontin-induced lung metastasis in BalB/c mice.

PubMed

Kang, Chi Gu; Im, Eunji; Lee, Hyo-Jeong; Lee, Eun-Ok

2017-05-01

Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer deaths in both men and women in the United States. It has been recently demonstrated that osteopontin (OPN) effectively inhibits cofilin activity through the focal adhesion kinase (FAK)/AKT/Rho-associated kinase (ROCK) pathway to induce the invasion of human non-small cell lung cancer (NSCLC) cells. Plumbagin was isolated from the roots of the medicinal plant Plumbago zeylanica L. and has been reported to possess anticancer activities. However, the molecular mechanisms by which plumbagin inhibits the invasion of cancer cells is still unclear. In this study, the anti-invasive and anti-metastatic mechanisms of plumbagin were investigated in OPN-treated NSCLC A549 cells. OPN effectively induced the motility and invasion of NSCLC A549 cells and H1299 cells, which was strongly suppressed by plumbagin with no evidence of cytotoxicity. In addition, lamellipodia formation at the leading edge of cells by OPN was dramatically decreased in plumbagin-treated cells. Plumbagin caused an effective inhibition in OPN-induced the expression of ROCK1 as well as the phosphorylation of LIM kinase 1 and 2 (LIMK1/2), and cofilin. OPN-induced the phosphorylation of FAK and AKT was impaired without affecting their total forms by plumbagin treatment. OPN facilitated metastatic lung colonization, which was effectively suppressed in plumbagin-treated mice. Taken together, these results suggest that plumbagin reduces OPN-induced the invasion of NSCLC A549 cells, which resulted from inhibiting the ROCK pathway mediated by the FAK/AKT pathway and suppresses lung metastasis in vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Lingling, E-mail: liulingling2012@163.com; Luo, Qing, E-mail: qing.luo@cqu.edu.cn; Sun, Jinghui, E-mail: sunjhemail@163.com

Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs andmore » reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.« less

A mammalian melanopsin in the retina of a fresh water turtle, the red-eared slider (Trachemys scripta elegans).

PubMed

Dearworth, James R; Selvarajah, Brian P; Kalman, Ross A; Lanzone, Andrew J; Goch, Abraham M; Boyd, Alison B; Goldberg, Laura A; Cooper, Lori J

2011-01-28

A mammalian-like melanopsin (Opn4m) has been found in all major vertebrate classes except reptile. Since the pupillary light reflex (PLR) of the fresh water turtle takes between 5 and 10 min to achieve maximum constriction, and since photosensitive retinal ganglion cells (ipRGCs) in mammals use Opn4m to control their slow sustained pupil responses, we hypothesized that a Opn4m homolog exists in the retina of the turtle. To identify its presence, retinal tissue was dissected from seven turtles, and total RNA extracted. Reverse transcriptase-polymerase chain reactions (RT-PCRs) were carried out to amplify gene sequences using primers targeting the highly conserved core region of Opn4m, and PCR products were analyzed by gel electrophoresis and sequenced. Sequences derived from a 1004-bp PCR product were compared to those stored in GenBank by the basic local alignment search tool (BLAST) algorithm and returned significant matches to several Opn4ms from other vertebrates including chicken. Quantitative real-time PCR (qPCR) was also carried out to compare expression levels of Opn4m in different tissues. The normalized expression level of Opn4m in the retina was higher in comparison to other tissue types: iris, liver, lung, and skeletal muscle. The results suggest that Opn4m exists in the retina of the turtle and provides a possible explanation for the presence of a slow PLR. The turtle is likely to be a useful model for further understanding the photoreceptive mechanisms in the retina which control the dynamics of the PLR. Copyright © 2010 Elsevier Ltd. All rights reserved.

Serum osteopontin concentration is decreased by exercise-induced fat loss but is not correlated with body fat percentage in obese humans.

PubMed

You, Jeong Soon; Ji, Hye-In; Chang, Kyung Ja; Yoo, Myung Chul; Yang, Hyung-In; Jeong, In-Kyung; Kim, Kyoung Soo

2013-08-01

To evaluate the extent to which fat mass contributes to serum osteopontin (OPN) concentration, we investigated whether serum OPN levels are decreased by exercise-induced fat mass loss and whether they are associated with body fat percentage in obese humans. Twenty‑three female college students were recruited to participate in an 8‑week body weight control program. Body composition [body weight, soft lean mass, body fat mass, body fat percentage, waist-hip ratio and body mass index (BMI)] were assessed prior to and following the program. Serum lipid profiles and serum adiponectin, leptin and osteopontin levels were measured from serum collected prior to and following the program. To understand the effect of fat mass loss on the serum levels of adipokine, which is mainly produced in adipose tissue, the leptin and adiponectin levels were also measured prior to and following the program. Serum leptin levels (mean ± standard error of the mean) decreased significantly following the program (from 9.82±0.98 to 7.23±0.67 ng/ml) and were closely correlated with body fat percentage. In addition, serum adiponectin levels were negatively correlated with body fat percentage, while serum adiponectin levels were not significantly altered. By contrast, serum OPN levels decreased significantly following the program (from 16.03±2.34 to 10.65±1.22 ng/ml). However, serum OPN levels were not correlated with body fat percentage, suggesting that serum OPN levels are controlled by several other factors in humans. In conclusion, a high expression of OPN in adipose tissues may not be correlated with serum OPN levels in obese humans. Thus, tissues or physiological factors other than fat mass may have a greater contribution to the serum OPN levels.

Unique Variants in OPN1LW Cause Both Syndromic and Nonsyndromic X-Linked High Myopia Mapped to MYP1.

PubMed

Li, Jiali; Gao, Bei; Guan, Liping; Xiao, Xueshan; Zhang, Jianguo; Li, Shiqiang; Jiang, Hui; Jia, Xiaoyun; Yang, Jianhua; Guo, Xiangming; Yin, Ye; Wang, Jun; Zhang, Qingjiong

2015-06-01

MYP1 is a locus for X-linked syndromic and nonsyndromic high myopia. Recently, unique haplotypes in OPN1LW were found to be responsible for X-linked syndromic high myopia mapped to MYP1. The current study is to test if such variants in OPN1LW are also responsible for X-linked nonsyndromic high myopia mapped to MYP1. The proband of the family previously mapped to MYP1 was initially analyzed using whole-exome sequencing and whole-genome sequencing. Additional probands with early-onset high myopia were analyzed using whole-exome sequencing. Variants in OPN1LW were selected and confirmed by Sanger sequencing. Long-range and second PCR were used to determine the haplotype and the first gene of the red-green gene array. Candidate variants were further validated in family members and controls. The unique LVAVA haplotype in OPN1LW was detected in the family with X-linked nonsyndromic high myopia mapped to MYP1. In addition, this haplotype and a novel frameshift mutation (c.617_620dup, p.Phe208Argfs*51) in OPN1LW were detected in two other families with X-linked high myopia. The unique haplotype cosegregated with high myopia in the two families, with a maximum LOD score of 3.34 and 2.31 at θ = 0. OPN1LW with the variants in these families was the first gene in the red-green gene array and was not present in 247 male controls. Reevaluation of the clinical data in both families with the unique haplotype suggested nonsyndromic high myopia. Our study confirms the findings that unique variants in OPN1LW are responsible for both syndromic and nonsyndromic X-linked high myopia mapped to MYP1.

Alterations in osteopontin modify muscle size in females in both humans and mice.

PubMed

Hoffman, Eric P; Gordish-Dressman, Heather; McLane, Virginia D; Devaney, Joseph M; Thompson, Paul D; Visich, Paul; Gordon, Paul M; Pescatello, Linda S; Zoeller, Robert F; Moyna, Niall M; Angelopoulos, Theodore J; Pegoraro, Elena; Cox, Gregory A; Clarkson, Priscilla M

2013-06-01

An osteopontin (OPN; SPP1) gene promoter polymorphism modifies disease severity in Duchenne muscular dystrophy, and we hypothesized that it might also modify muscle phenotypes in healthy volunteers. Gene association studies were carried out for OPN (rs28357094) in the FAMuSS cohort (n = 752; mean ± SD age = 23.7 ± 5.7 yr). The phenotypes studied included muscle size (MRI), strength, and response to supervised resistance training. We also studied 147 young adults that had carried out a bout of eccentric elbow exercise (age = 24.0 ± 5.2 yr). Phenotypes analyzed included strength, soreness, and serum muscle enzymes. In the FAMuSS cohort, the G allele was associated with 17% increase in baseline upper arm muscle volume only in women (F = 26.32; P = 5.32 × 10), explaining 5% of population variance. In the eccentric damage cohort, weak associations of the G allele were seen in women with both baseline myoglobin and elevated creatine kinase. The sexually dimorphic effects of OPN on muscle were also seen in OPN-null mice. Five of seven muscle groups examined showed smaller size in OPN-null female mice, whereas two were smaller in male mice. The query of OPN gene transcription after experimental muscle damage in mice showed rapid induction within 12 h (100-fold increase from baseline), followed by sustained high-level expression through 16 d of regeneration before falling to back to baseline. OPN is a sexually dimorphic modifier of muscle size in normal humans and mice and responds to muscle damage. The OPN gene is known to be estrogen responsive, and this may explain the female-specific genotype effects in adult volunteers.

Endogenous osteopontin promotes ozone-induced neutrophil recruitment to the lungs and airway hyperresponsiveness to methacholine

PubMed Central

Barreno, Ramon X.; Richards, Jeremy B.; Schneider, Daniel J.; Cromar, Kevin R.; Nadas, Arthur J.; Hernandez, Christopher B.; Hallberg, Lance M.; Price, Roger E.; Hashmi, Syed S.; Blackburn, Michael R.; Haque, Ikram U.

2013-01-01

Inhalation of ozone (O3), a common environmental pollutant, causes pulmonary injury, pulmonary inflammation, and airway hyperresponsiveness (AHR) in healthy individuals and exacerbates many of these same sequelae in individuals with preexisting lung disease. However, the mechanisms underlying these phenomena are poorly understood. Consequently, we sought to determine the contribution of osteopontin (OPN), a hormone and a pleiotropic cytokine, to the development of O3-induced pulmonary injury, pulmonary inflammation, and AHR. To that end, we examined indices of these aforementioned sequelae in mice genetically deficient in OPN and in wild-type, C57BL/6 mice 24 h following the cessation of an acute (3 h) exposure to filtered room air (air) or O3 (2 parts/million). In wild-type mice, O3 exposure increased bronchoalveolar lavage fluid (BALF) OPN, whereas immunohistochemical analysis demonstrated that there were no differences in the number of OPN-positive alveolar macrophages between air- and O3-exposed wild-type mice. O3 exposure also increased BALF epithelial cells, protein, and neutrophils in wild-type and OPN-deficient mice compared with genotype-matched, air-exposed controls. However, following O3 exposure, BALF neutrophils were significantly reduced in OPN-deficient compared with wild-type mice. When airway responsiveness to inhaled acetyl-β-methylcholine chloride (methacholine) was assessed using the forced oscillation technique, O3 exposure caused hyperresponsiveness to methacholine in the airways and lung parenchyma of wild-type mice, but not OPN-deficient mice. These results demonstrate that OPN is increased in the air spaces following acute exposure to O3 and functionally contributes to the development of O3-induced pulmonary inflammation and airway and lung parenchymal hyperresponsiveness to methacholine. PMID:23666750

α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression

PubMed Central

Jang, Min A.; Lee, Seung Jin; Baek, Seung Eun; Park, So Youn; Choi, Young Whan; Kim, Chi Dae

2017-01-01

α-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in Schisandra chinensis (SC), a well-known medicinal herb that ameliorates cardiovascular symptoms. Thus, we examined the effect of ICB on vascular smooth muscle cell (VSMC) proliferation, a key feature of diverse vascular diseases. When VSMCs primary cultured from rat thoracic aorta were stimulated with PDGF (1–10 ng/ml), cell proliferation and osteopontin (OPN) expression were concomitantly up-regulated, but these effects were attenuated when cells were treated with MPIIIB10, a neutralizing monoclonal antibody for OPN. In aortic tissues exposed to PDGF, sprouting VSMC numbers increased, which was attenuated in tissues from OPN-deficient mice. Furthermore, VSMC proliferation and OPN expression induced by PDGF were attenuated dose-dependently by ICB (10 or 30 μg/ml). Reporter assays conducted using OPN promoter-luciferase constructs showed that the promoter region 538–234 bp of the transcription start site was responsible for transcriptional activity enhancement by PDGF, which was significantly inhibited by ICB. Putative binding sites for AP-1 and C/EBPβ in the indicated promoter region were suggested by TF Search, and increased binding of AP-1 and C/EBPβ in PDGF-treated VSMCs was demonstrated using a ChIP assay. The increased bindings of AP-1 and C/EBPβ into OPN promoter were attenuated by ICB. Moreover, the PDGF-induced expression of OPN was markedly attenuated in VSMCs transfected with siRNA for AP-1 and C/EBPβ. These results indicate that ICB inhibit VSMC proliferation by inhibiting the AP-1 and C/EBPβ signaling pathways and thus downregulating OPN expression. PMID:28114367

In Vivo Overexpression of Tissue-Nonspecific Alkaline Phosphatase Increases Skeletal Mineralization and Affects the Phosphorylation Status of Osteopontin

PubMed Central

Narisawa, Sonoko; Yadav, Manisha C.; Millán, José Luis

2013-01-01

Functional ablation of tissue-nonspecific alkaline phosphatase (TNAP) (Alpl−/− mice) leads to hypophosphatasia, characterized by rickets/osteomalacia attributable to elevated levels of extracellular inorganic pyrophosphate, a potent mineralization inhibitor. Osteopontin (OPN) is also elevated in the plasma and skeleton of Alpl−/− mice. Phosphorylated OPN is known to inhibit mineralization, however, the phosphorylation status of the increased OPN found in Alpl−/− mice is unknown. Here, we generated a transgenic mouse line expressing human TNAP under control of an osteoblast-specific Col1a1 promoter (Col1a1-Tnap). The transgene is expressed in osteoblasts, periosteum, and cortical bones, and plasma levels of TNAP in mice expressing Col1a1-Tnap are 10-20 times higher than those of wild-type mice. The Col1a1-Tnap animals are healthy and exhibit increased bone mineralization by microCT analysis. Crossbreeding of Col1a1-Tnap transgenic mice to Alpl−/− mice rescues the lethal hypophosphatasia phenotype characteristic of this disease model. Osteoblasts from [Col1a1-Tnap] mice mineralize better than non-transgenic controls and osteoblasts from [Col1a1-Tnap+/−; Alpl−/−] mice are able to mineralize to the level of Alpl+/− heterozygous osteoblasts, while Alpl−/− osteoblasts show no mineralization. We found that the increased levels of OPN in bone tissue of Alpl−/− mice are comprised of phosphorylated forms of OPN while WT and [Col1a1-Tnap+/−; Alpl−/−] mice had both phosphorylated and dephosphorylated forms of OPN. OPN from [Col1a1-Tnap] osteoblasts were more phosphorylated than non-transgenic control cells. Titanium dioxide-liquid chromatography and tandem mass spectrometry analysis revealed that OPN peptides derived from Alpl−/− bone and osteoblasts yielded a higher proportion of phosphorylated peptides than samples from WT mice, and at least two phosphopeptides, p(S174FQVS178DEQY182PDAT186DEDLT191)SHMK and FRIp(S299HELES304S305S306S307)EVN, with one non-localized site each, appear to be preferred sites of TNAP action on OPN. Our data suggest that the pro-mineralization role of TNAP may be related not only to its accepted pyrophosphatase activity but also to its ability to modify the phosphorylation status of OPN. PMID:23427088

Osteopontin regulates adhesion of calcium oxalate crystals to renal epithelial cells.

PubMed

Yasui, Takahiro; Fujita, Keiji; Asai, Kiyofumi; Kohri, Kenjiro

2002-02-01

The association of calcium crystals with renal tubular cells is an important factor during the formation of urinary stones. We previously reported the strong expression of osteopontin (OPN) on renal tubular cells in the stone-forming kidney, suggesting that OPN plays a role in the crystal-cell interaction. In the present study, we examined the biological consequences of inhibiting OPN expression at the translational level on the formation and adhesion of crystals. We synthesized antisense OPN expression vector (pTet-OPNas) using the tetracycline-regulated expression system. The pTet-OPNas was constructed using a mouse OPN cDNA sequence in an inverted (antisense) orientation. Two clones (NRK-52E/ASs) were identified by transfection of pTet-OPNas into NRK-52E cells and they showed a marked reduction of OPN synthesis in the absence of tetracycline. Calcium oxalate (CaOx) crystal suspension was spread homogeneously on top of the NRK-52E cells. After incubation, the association of CaOx crystals and cells was visualized by scanning electron microscopy. Intact NRK-52E cells, NRK-52E cells transfected with empty vector and tetracycline-treated antisense clones (NRK-52E/ASs), under identical conditions, were associated with CaOx crystals. In contrast, the expression of antisense OPN prevented the association of CaOx crystals with NRK-52E cells. Osteopontin plays a crucial role in the adhesion process of CaOx crystals to renal tubular cells in stone formation.

Preoperative planning and real-time assisted navigation by three-dimensional individual digital model in partial nephrectomy with three-dimensional laparoscopic system.

PubMed

Wang, Dongwen; Zhang, Bin; Yuan, Xiaobin; Zhang, Xuhui; Liu, Chen

2015-09-01

To evaluate the feasibility and effectiveness of preoperative planning and real-time assisted surgical navigation for three-dimensional laparoscopic partial nephrectomy under the guidance of three-dimensional individual digital model (3D-IDM) created using three-dimensional medical image reconstructing and guiding system (3D-MIRGS). Between May 2012 and February 2014, 44 patients with cT1 renal tumors underwent retroperitoneal laparoscopic partial nephrectomy (LPN) using a three-dimensional laparoscopic system. The 3D-IDMs were created using the 3D-MIRGS in 21 patients (3D-MIRGS group) between February 2013 and February 2014. After preoperative planning, operations were real-time assisted using composite 3D-IDMs, which were fused with two-dimensional retrolaparoscopic images. The remaining 23 patients underwent surgery without 3D-MIRGS between May 2012 and February 2013; 14 of these patients were selected as a control group. Preoperative aspects and dimensions used for an anatomical score, "radius; exophytic/endophytic; nearness; anterior/posterior; location" nephrometry score, tumor size, operative time (OT), segmental renal artery clamping (SRAC) time, estimated blood loss (EBL), postoperative hospitalization, the preoperative serum creatinine level and ipsilateral glomerular filtration rate (GFR), as well as postoperative 6-month data were compared between groups. All the SRAC procedures were technically successful, and each targeted tumor was excised completely; final pathological margin results were negative. The OT was shorter (159.0 vs. 193.2 min; p < 0.001), and EBL (148.1 vs. 176.1 mL; p < 0.001) was reduced in the 3D-MIRGS group compared with controls. No statistically significant differences in SRAC time or postoperative hospitalization were found between the groups. Neither group showed any statistically significant increases in serum creatinine level or decreases in ipsilateral GFR postoperatively. Preoperative planning and real-time assisted surgical navigation using the 3D-IDM reconstructed from 3D-MIRGS and combined with the 3D laparoscopic system can facilitate LPN and result in precise SRAC and accurate excision of tumor that is both effective and safe.

High-fidelity simulation-based team training in urology: evaluation of technical and nontechnical skills of urology residents during laparoscopic partial nephrectomy.

PubMed

Abdelshehid, Corollos S; Quach, Stephen; Nelson, Corey; Graversen, Joseph; Lusch, Achim; Zarraga, Jerome; Alipanah, Reza; Landman, Jaime; McDougall, Elspeth M

2013-01-01

The use of low-risk simulation training for resident education is rapidly expanding as teaching centers integrate simulation-based team training (SBTT) sessions into their education curriculum. SBTT is a valuable tool in technical and communication skills training and assessment for residents. We created a unique SBTT scenario for urology residents involving a laparoscopic partial nephrectomy procedure. Urology residents were randomly paired with a certified registered nurse anesthetists or an anesthesia resident. The scenario incorporated a laparoscopic right partial nephrectomy utilizing a unique polyvinyl alcohol kidney model with an embedded 3cm lower pole exophytic tumor and the high-fidelity SimMan3G mannequin. The Urology residents were instructed to pay particular attention to the patient's identifying information provided at the beginning of the case. Two scripted events occurred, the patient had an anaphylactic reaction to a drug and, after tumor specimen was sent for a frozen section, the confederate pathologist called into the operating room (OR) twice, first with the wrong patient name and subsequently with the wrong specimen. After the scenario was complete, technical performance and nontechnical performance were evaluated and assessed. A debriefing session followed the scenario to discuss and assess technical performance and interdisciplinary nontechnical communication between the team. All Urology residents (n = 9) rated the SBTT scenario as a useful tool in developing communication skills among the OR team and 88% rated the model as useful for technical skills training. Despite cuing to note patient identification, only 3 of 9 (33%) participants identified that the wrong patient information was presented when the confederate "pathologist" called in to report pathology results. All urology residents rated SBTT sessions as useful for the development of communication skills between different team members and making residents aware of unlikely but potential critical errors in the OR. We will continue to use SBTT as a useful method to develop resident technical and nontechnical skills outside of the high-risk operating environment. Copyright © 2013 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

"Zero ischemia" partial nephrectomy: novel laparoscopic and robotic technique.

PubMed

Gill, Inderbir S; Eisenberg, Manuel S; Aron, Monish; Berger, Andre; Ukimura, Osamu; Patil, Mukul B; Campese, Vito; Thangathurai, Duraiyah; Desai, Mihir M

2011-01-01

Ischemic injury impacts renal function outcomes following partial nephrectomy. Efforts to minimize, better yet, eliminate renal ischemia are imperative. Describe a novel technique of "zero ischemia" laparoscopic (LPN) and robotic-assisted (RAPN) partial nephrectomy. Data were prospectively collected into an institutional review board-approved database. Fifteen consecutive patients underwent zero ischemia procedures: LPN (n=12), RAPN (n=3). Included were all candidates for LPN or RAPN, irrespective of tumor complexity, including tumors that were central (n=9; 60%), hilar (n=1), in solitary kidney (n=1), in patients with chronic kidney disease grade 3 or greater (n=3). Anesthesia-related monitoring included pulmonary artery catheter (ie, Swan-Ganz), transesophageal echocardiography, cerebral oximetry, electroencephalographic bispectral index, mixed venous oxygen measurements, and vigorous hydration/diuresis. Pharmacologically induced hypotension was carefully timed to correspond with excision of the deepest aspect of the tumor. Renal parenchymal reconstruction was completed under normotension, ensuring complete hemostasis. Intraoperative and early postoperative data were collected prospectively. All cases were successfully completed without hilar clamping. Ischemia time was zero in all cases. Median tumor size was 2.5 cm (range: 1-4); operative time was 3 h (range: 1.3-6); blood loss was 150 ml (range: 20-400); and hospital stay was 3 d (range: 2-19). Nadir mean arterial pressure ranged from 52-65 mm Hg (median: 60), typically for 1-5 min. No patient had intraoperative transfusion or complication, acute or delayed renal hemorrhage, or hypotension-related sequelae. Postoperative complications (n=5) included urine retention (n=1), septicemia from presumed prostatitis (n=1), atrial fibrillation (n=1), urine leak (n=2). Pathology confirmed renal cell carcinoma in 13 patients (87%), all with negative margins. Median pre- and postoperative serum creatinine (0.9 mg/dl and 0.95 mg/dl, respectively) and estimated glomerular filtration rate (eGFR) (75.3 and 72.9, respectively) were comparable. Median absolute and percent change in discharge serum creatinine and eGFR were 0 and 0%, respectively. A novel zero ischemia technique for RAPN and LPN for substantial renal tumors is presented. The initial experience is encouraging. Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Multi-institutional analysis of robotic partial nephrectomy for hilar versus nonhilar lesions in 446 consecutive cases.

PubMed

Dulabon, Lori M; Kaouk, Jihad H; Haber, Georges-Pascal; Berkman, Douglas S; Rogers, Craig G; Petros, Firas; Bhayani, Sam B; Stifelman, Michael D

2011-03-01

Minimally invasive approaches to partial nephrectomy have been rapidly gaining popularity but require advanced laparoscopic surgical skills. Renal hilar tumors, due to their anatomic location, pose additional technical challenges to the operating surgeon. We compared the outcomes of robot-assisted partial nephrectomy (RPN) for hilar and nonhilar tumors in our large multicenter contemporary series of patients. We retrospectively reviewed prospectively collected data on 446 consecutive patients who underwent RPN by renal surgeons experienced in minimally invasive techniques at four academic institutions from June 2006 to March 2010. Patients were stratified into two groups: those with hilar lesions and those with nonhilar lesions. Patient demographics, operative outcomes, and postoperative outcomes, including oncologic outcomes, were recorded. Forty-one patients (9%) had hilar renal masses; 405 patients (91%) had nonhilar masses. There was no statistical differences in patient demographics except for larger median tumor size in the hilar cohort (3.2 cm vs 2.6 cm; p=0.001). The only significant difference in operative outcomes was an increase in warm ischemia times for the hilar group versus the nonhilar group (26.3±7.4 min vs 19.6±10.0 min; p=<0.0001). There were no differences in postoperative outcomes; however, there was a trend for increased risk of malignancy and higher stage tumors in the hilar lesion group. Final pathologic margin status was similar in both groups. Only one patient in the nonhilar group had evidence of recurrence at 21 mo. The study was limited by the lack of standard anatomic classification of renal tumors and the potential influence of the surgeons' prior robotic experience. The data represent the largest series of its kind and strongly suggest that RPN is a safe, effective, and feasible option for the minimally invasive approach to renal hilar tumors with no increased risk of adverse outcomes compared with nonhilar tumors in the hands of experienced robotic surgeons. Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus

PubMed Central

2013-01-01

Introduction Osteopontin (OPN) has been implicated as a mediator of Th17 regulation via type I interferon (IFN) receptor signaling and in macrophage activity at sites of tissue repair. This study assessed whether increased circulating plasma OPN (cOPN) precedes development of organ damage in pediatric systemic lupus erythematosus (pSLE) and compared it to circulating plasma neutrophil gelatinase-associated lipocalin (cNGAL), a predictor of increased SLE disease activity. Methods cOPN and cNGAL were measured in prospectively followed pSLE (n = 42) and adult SLE (aSLE; n = 23) patients and age-matched controls. Time-adjusted cumulative disease activity and disease damage were respectively assessed using adjusted-mean SLE disease activity index (SLEDAI) (AMS) and SLICC/ACR damage index (SDI). Results Compared to controls, elevated cOPN and cNGAL were observed in pSLE and aSLE. cNGAL preceded worsening SLEDAI by 3-6 months (P = 0.04), but was not associated with increased 6-month AMS. High baseline cOPN, which was associated with high IFNalpha activity and expression of autoantibodies to nucleic acids, positively correlated with 6-month AMS (r = 0.51 and 0.52, P = 0.001 and 0.01 in pSLE and aSLE, respectively) and was associated with SDI increase at 12 months in pSLE (P = 0.001). Risk factors for change in SDI in pSLE were cOPN (OR 7.5, 95% CI [2.9-20], P = 0.03), but not cNGAL, cumulative prednisone, disease duration, immunosuppression use, gender or ancestry using univariate and multivariate logistic regression. The area under the curve (AUC) when generating the receiver-operating characteristic (ROC) of baseline cOPN sensitivity and specificity for the indication of SLE patients with an increase of SDI over a 12 month period is 0.543 (95% CI 0.347-0.738; positive predictive value 95% and negative predictive value 38%). Conclusion High circulating OPN levels preceded increased cumulative disease activity and organ damage in SLE patients, especially in pSLE, and its value as a predictor of poor outcome should be further validated in large longitudinal cohorts. PMID:23343383

The involvement of osteopontin and matrix metalloproteinase- 9 in the migration of endometrial epithelial cells in patients with endometriosis.

PubMed

Yang, Mei; Jiang, Chunfan; Chen, Hua; Nian, Yan; Bai, Zhimiao; Ha, Chunfang

2015-08-20

Endometriosis, which shares certain characteristics with cancers, may cause abnormal expression of proteins involved in cell migration. Endometrial epithelial cells (EECs) are believed to play an important role in endometriotic migration. The aim of this study was to investigate the relationship between the expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in endometriotic migration. We performed primary culture of EECs and investigated the expression of OPN and MMP-9 in EECs regulated by 17beta-estradiol (E2). OPN-specific siRNA interference was used to down-regulate OPN and to explore the corresponding change in MMP-9 expression. Real-time RT-PCR, western blot analysis and flow cytometry were used to determine the expression levels of OPN and MMP-9. Gelatin zymography was performed to observe the enzymatic activity of MMP-9 in conditioned media. Transwell and wound scratch assays were performed to investigate the migration ability of EECs. The expression levels of OPN and MMP-9 in normal EECs (NEECs) were inferior to those in EECs from patients with endometriosis (EEECs). The expression levels of OPN and MMP-9 from stage III/IV EEECs and secretory-phase EECs were higher than those of stage I/II EEECs or proliferative-phase EECs. The expression levels of OPN and MMP-9 in EEECs were increased by E2 treatment and remarkably decreased by siRNA interference. Active MMP-9 expression increased with E2 treatment and decreased with siRNA treatment in EEECs compared with the same treatments in NEECs. The migratory abilities of EEECs were enhanced after cells were treated with E2; in contrast, these abilities were reduced by siRNA interference. In NEECs, active MMP-9 and cellular migration abilities were only minimally influenced by E2 and siRNA treatment. The present study suggests that the up-regulation of MMP-9 via activation of OPN induced by estrogen may correlate with the migration of endometrial epithelial cells in patients with endometriosis.

Intraoperative laparoscopic complications for urological cancer procedures

PubMed Central

Montes, Sergio Fernández-Pello; Rodríguez, Ivan Gonzalez; Ugarteburu, Rodrigo Gil; Villamil, Luis Rodríguez; Mendez, Begoña Diaz; Gil, Patricio Suarez; Madera, Javier Mosquera

2015-01-01

AIM: To structure the rate of intraoperative complications that requires an intraoperative or perioperative resolution. METHODS: We perform a literature review of Medline database. The research was focused on intraoperative laparoscopic procedures inside the field of urological oncology. General rate of perioperative complications in laparoscopic urologic surgery is described to be around 12.4%. Most of the manuscripts published do not make differences between pure intraoperative, intraoperative with postoperative consequences and postoperative complications. RESULTS: We expose a narrative statement of complications, possible solutions and possible preventions for most frequent retroperitoneal and pelvic laparoscopic surgery. We expose the results with the following order: retroperitoneal laparoscopic surgery (radical nephrectomy, partial nephrectomy, nephroureterectomy and adrenalectomy) and pelvic laparoscopic surgery (radical prostatectomy and radical cystectomy). CONCLUSION: Intraoperative complications vary from different series. More scheduled reports should be done in order to better understand the real rates of complications. PMID:25984519

Laparoscopic Donor Nephrectomy: Early Experience at a Single Center in Pakistan.

PubMed

Mohsin, Rehan; Shehzad, Asad; Bajracharya, Uspal; Ali, Bux; Aziz, Tahir; Mubarak, Muhammed; Hashmi, Altaf; Rizvi, Adibul Hasan

2018-04-01

Laparoscopic donor nephrectomy has become the criterion standard for kidney retrieval from living donors. There is no information on the experience and outcomes of laparoscopic donor nephrectomy in Pakistan. The objective of the study was to identify benefits and harms of using laparoscopic compared with open nephrectomy techniques for renal allograft retrieval. In this a retrospective study, patient files from May 2014 to September 2015 were analyzed. Patients were divided into 2 groups: those with open donor nephrectomy and those with laparoscopic donor nephrectomy. Donor case files and operative notes were analyzed for age, sex, laterality, body mass index, warm ischemia time, perioperative and postoperative complications, surgery time, and length of hospital stay. Finally, serum creatinine patterns of both donors and recipients were analyzed. Data were analyzed using SPSS version 10 (SPSS: An IBM Company, IBM Corporation, Armonk, NY, USA). Of 388 total donors, 190 (49%) had open donor nephrectomy and 198 (51%) had laparoscopic donor nephrectomy. For both groups, most donors were older than 25 years with male preponderance. Left-to-right kidney donation ratio was markedly higher in the laparoscopic group than in the open donor nephrectomy group, with 6 cases of double renal artery also included in this study. There were no significant differences in surgery times between the 2 groups, whereas the laparoscopic donor nephrectomy group had shorter hospital stay. Analgesic requirements were markedly shorter in the laparoscopic donor nephrectomy group. The 1-year graft function was not significantly different between the 2 groups. The results for laparoscopic donor nephrectomy were comparable to those for open donor nephrectomy, and its acceptability was high. Laparoscopic donor nephrectomy should be the preferred approach for procuring the kidney graft.

Soluble Mesothelin Related Peptide (SMRP) and Osteopontin (OPN) as Early Detection Markers for Malignant Mesothelioma (MM) — EDRN Public Portal

Cancer.gov

Phase I: - Identification and assemblage of representative cohorts of individuals with MM, no malignancies but increased risk for MM due to asbestos exposure, and (optionally) lung malignancies other than MM Phase II (A) - Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals with a clinical diagnosis of malignant mesothelioma from individuals who are asbestos-exposed but without a clinical diagnosis of malignant mesothelioma. Phase II (B) – Determine the comparability of analyte values across contributing centers and determine covariates that influence analyte levels Phase II (C) – Determine the sensitivity and specificity of SMRP and OPN, alone and in combination, in distinguishing individuals with MM from those without. Phase III. Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals who would subsequently develop malignant mesothelioma from matched individuals who did not subsequently develop malignant mesothelioma. Phase IV. Determine the sensitivity and specificity of SMRP and OPN in other populations of interest.

Osteopontin is a Novel Marker of Pancreatic Ductal Tissues and of Undifferentiated Pancreatic Precursors in Mice

PubMed Central

Kilic, Gamze; Wang, Junfeng; Sosa-Pineda, Beatriz

2008-01-01

Matricellular proteins mediate both tissue morphogenesis and tissue homeostasis in important ways because they modulate cell-matrix and cell-cell interactions. In this study, we found that the matricellular protein osteopontin (Opn) is a novel marker of undifferentiated pancreatic precursors and pancreatic ductal tissues in mice. Our analysis also underscored a specific, dynamic profile of Opn expression in embryonic pancreatic tissues that suggests the participation of this protein’s function in processes involving cell migration, cell-cell interactions, or both. Surprisingly, our analysis of Opn-deficient pancreata did not reveal obvious alterations in the morphology or differentiation of these tissues. Therefore, in embryonic pancreatic tissues, it is possible that other proteins act redundantly to Opn or that this protein’s function is dispensable for pancreas development. Finally, the maintenance of Opn expression in pancreatic tissues of adults argues for a possible function of this protein in injury and pathologic responses. PMID:16518820

Anti-osteopontin monoclonal antibody prevents ovariectomy-induced osteoporosis in mice by promotion of osteoclast apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Bo; PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing; Dai, Jianxin

Highlight: • We first report that anti-osteopontin mAb could protect osteoporosis in mice. • Anti-osteopontin mAb could promote the osteoclast apoptosis. • Targeting osteopontin might have therapeutic potentials for osteoporosis. - Abstract: Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation. In vitro assay showed that 23C3 mAb reduced osteoclasts (OCs)-mediated bone resorptionmore » through promotion of mature OC apoptosis. Thus, the study has important implications for understanding the role of OPN in OC bone resorption and survival, and OPN antagonists may have therapeutic potential for osteoporosis and other osteopenic diseases.« less

A multimodal imaging framework for enhanced robot-assisted partial nephrectomy guidance

NASA Astrophysics Data System (ADS)

Halter, Ryan J.; Wu, Xiaotian; Hartov, Alex; Seigne, John; Khan, Shadab

2015-03-01

Robot-assisted laparoscopic partial nephrectomies (RALPN) are performed to treat patients with locally confined renal carcinoma. There are well-documented benefits to performing partial (opposed to radical) kidney resections and to using robot-assisted laparoscopic (opposed to open) approaches. However, there are challenges in identifying tumor margins and critical benign structures including blood vessels and collecting systems during current RALPN procedures. The primary objective of this effort is to couple multiple image and data streams together to augment visual information currently provided to surgeons performing RALPN and ultimately ensure complete tumor resection and minimal damage to functional structures (i.e. renal vasculature and collecting systems). To meet this challenge we have developed a framework and performed initial feasibility experiments to couple pre-operative high-resolution anatomic images with intraoperative MRI, ultrasound (US) and optical-based surface mapping and kidney tracking. With these registered images and data streams, we aim to overlay the high-resolution contrast-enhanced anatomic (CT or MR) images onto the surgeon's view screen for enhanced guidance. To date we have integrated the following components of our framework: 1) a method for tracking an intraoperative US probe to extract the kidney surface and a set of embedded kidney markers, 2) a method for co-registering intraoperative US scans with pre-operative MR scans, and 3) a method for deforming pre-op scans to match intraoperative scans. These components have been evaluated through phantom studies to demonstrate protocol feasibility.

Targeting Extracellular Matrix Glycoproteins in Metastases for Tumor-Initiating Cell Therapy

DTIC Science & Technology

2016-04-01

effects of OPN-targeting system carrying a hedgehog pathway inhibitor (month 3-12) (not completed)  What was accomplished under these goals? Major...Preparation of prostaspheres 4 • objective 2: Evaluate the therapeutic effects of OPN-targeting system carrying a hedgehog pathway inhibitor...encapsulate a hedgehog pathway inhibitor cyclopamine (CP), and the data are as follows: Average diameter (nm) PDI Zeta potential (mV) Blank LN, no OPN

Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells.

PubMed

Liu, Lingling; Luo, Qing; Sun, Jinghui; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

2018-03-01

Osteopontin (OPN) is a chemokine-like extracellular matrix-associated protein involved in the migration of bone marrow-derived mesenchymal stem cells (BMSCs). An increasing number of studies have found that chromatin organization may affect cellular migration. However, whether OPN regulates chromatin organization is not understood, nor are the underlying molecular mechanisms. In this study, we investigated the link between chromatin organization and BMSC migration and demonstrated that OPN-mediated BMSC migration leads to elevated levels of heterochromatin marker histone H3 lysine 27 trimethylation (H3K27me3) through the methyltransferase EZH2. The expression of EZH2 reorganizes the chromatin structure of BMSCs. Pharmacological inhibition or depletion of EZH2 blocks BMSC migration. Moreover, using an atomic force microscope (AFM), we found that chromatin decondensation alters the mechanical properties of the nucleus. In addition, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) signals represses OPN-promoted chromatin condensation and cell migration. Thus, our results identify a mechanism by which ERK1/2 signalling drives specific chromatin modifications in BMSCs, which alters chromatin organization and thereby enables OPN-mediated BMSC migration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Osteopontin and the dento-osseous pathobiology of X-linked hypophosphatemia.

PubMed

Boukpessi, Tchilalo; Hoac, Betty; Coyac, Benjamin R; Leger, Thibaut; Garcia, Camille; Wicart, Philippe; Whyte, Michael P; Glorieux, Francis H; Linglart, Agnès; Chaussain, Catherine; McKee, Marc D

2017-02-01

Seven young patients with X-linked hypophosphatemia (XLH, having inactivating PHEX mutations) were discovered to accumulate osteopontin (OPN) at the sites of defective bone mineralization near osteocytes - the so-called hallmark periosteocytic (lacunar) "halos" of XLH. OPN was also localized in the pericanalicular matrix extending beyond the osteocyte lacunae, as well as in the hypomineralized matrix of tooth dentin. OPN, a potent inhibitor of mineralization normally degraded by PHEX, is a member of a family of acidic, phosphorylated, calcium-binding, extracellular matrix proteins known to regulate dental, skeletal, and pathologic mineralization. Associated with the increased amount of OPN (along with inhibitory OPN peptide fragments) in XLH bone matrix, we found an enlarged, hypomineralized, lacuno-canalicular network - a defective pattern of skeletal mineralization that decreases stiffness locally at: i) the cell-matrix interface in the pericellular environment of the mechanosensing osteocyte, and ii) the osteocyte's dendritic network of cell processes extending throughout the bone. Our findings of an excess of inhibitory OPN near osteocytes and their cell processes, and in dentin, spatially correlates with the defective mineralization observed at these sites in the skeleton and teeth of XLH patients. These changes likely contribute to the dento-osseous pathobiology of XLH, and participate in the aberrant bone adaptation and remodeling seen in XLH. Copyright © 2016 Elsevier Inc. All rights reserved.

[Expression of connective tissue growth factor (CTGF), osteopontin (OPN) and clinical significances in the laryngeal squamous cell carcinoma tissues].

PubMed

Li, Youzhong; Lu, Yongde; Ceng, Yici; Yang, Xinming

2007-02-01

To study the expressions of CTGF and OPN and detect their clinical value and correlation in the laryngeal squamous cell carcinoma tissues and paracancerous tissues. SP immunohistochemical method was used for the assays of CTGF and OPN on the routinely paraffin-embedded sections of surgical operated specimens of 41 cases with laryngeal squamous cell carcinoma and 20 ones with paracancerous tissues. The positive rate of CTGF and the score were significantly lower in cancer tissues than those in paracancerous tissues (61.0% vs 90.0%, P < 0.05; 2.41 +/- 1.60 vs 4.24 +/- 1.42, P < 0.01), but those of OPN were opposite (61.0% vs 15.0%, P < 0.01; 3. 10 +/- 1.63 vs 1.12 +/- 0.84, P < 0.01). The positive rates and scores of CTGF were significantly higher in the cases without-metastasis of lymph node and clinical stage T1 than those in the ones with-metastasis of lymph node and clinical stage T3 (P < 0.01) . The positive rates and scores of OPN were significantly lower in the cases without-metastasis of lymph node, clinical stage T1 and histological grade I those that in the ones with-metastasis of lymph node, Clinical stage T3 and histological grade III (P < 0.01). The closely negative correlation was found between the score of CTGF and that of OPN. The expression of CTGF and/or OPN might be important biological markers in reflecting the progression, biological behaviors, metastatic potential and prognosis of the laryngeal squamous cell carcinoma.

Relative to open surgery, minimally-invasive renal and ureteral pediatric surgery offers no improvement in 30-day complications, yet requires longer operative time: Data from the National Surgical Quality Improvement Program Pediatrics.

PubMed

Colaco, Marc; Hester, Austin; Visser, William; Rasper, Alison; Terlecki, Ryan

2018-05-01

Performance of minimally-invasive surgery (MIS) is increasing relative to open surgery. We sought to compare the contemporary rates of short-term complications of open versus laparoscopic renal and ureteral surgery in pediatric patients. A retrospective cross-sectional analysis of the National Surgical Quality Improvement Program Pediatrics database was performed of all cases in 2014 identified using CPT procedure codes for nephrectomy, partial nephrectomy (PN), ureteroneocystostomy (UNC), and pyeloplasty, and reviewed for postoperative complications. Univariate analysis was performed to determine 30-day complications, with comparison between open and MIS approaches. Receiver operator curve (ROC) analysis was performed to determine differences in body surface area (BSA) and age for open versus MIS. Review identified 207 nephrectomies, 72 PN, 920 UNC, and 625 pyeloplasties. MIS was associated with older age and larger BSA except for cases of UNC. Apart from PN, operative durations were longer with MIS. However, only PN was associated with significantly longer length of hospital stay (LOS). There was no difference in incidence of all other 30-day complications. When evaluating BSA via ROC, the area under the curve (AUC) was found to be 0.730 and was significant. Children with a BSA greater than 0.408 m 2 were more likely to have MIS (sensitivity, 66.9%; specificity, 69.3%). Regarding age, the AUC was 0.732. Children older than 637.5 days were more likely to have MIS (sensitivity, 72.8%; specificity, 63.3%). Pediatric MIS is associated with longer operative time for nephrectomy, but shorter LOS following PN. Surgical approach was not associated with difference in short-term complications.

Contemporary, age-based trends in the incidence and management of patients with early-stage kidney cancer.

PubMed

Tan, Hung-Jui; Filson, Christopher P; Litwin, Mark S

2015-01-01

Although kidney cancer incidence and nephrectomy rates have risen in tandem, clinical advances have generated new uncertainty regarding the optimal management of patients with small renal tumors, especially the elderly. To clarify existing practice patterns, we assessed contemporary trends in the incidence and management of patients with early-stage kidney cancer. Using Surveillance, Epidemiology, and End Results data, we identified adult patients diagnosed with T1aN0M0 kidney cancer from 2000 to 2010. We determined age-adjusted and age-specific incidence and management rates (i.e., nonoperative, ablation, partial nephrectomy [PN], and radical nephrectomy) per 100,000 adults and determined the average annual percent change (AAPC). Finally, we compared management groups using multinomial logistic regression accounting for patient characteristics, cancer information, and county-level measures for health. From 2000 to 2010, we identified 41,645 adults diagnosed with T1aN0M0 kidney cancer. Overall incidence increased from 3.7 to 7.0 per 100,000 adults (AAPC = 7.0%, P<0.001). Over the study interval, rates of PN (AAPC = 13.1%, P<0.001) increased substantially, becoming the most used treatment by 2010. Among the elderly, rates of nonoperative management and ablation approached nephrectomy rates for those aged 75 to 84 years and became the predominant strategy for patients older than 84 years. Adjusting for clinical, oncological, and environmental factors, older patients less frequently underwent PN and more often received ablative or nonoperative management (P<0.001). As the incidence of early-stage kidney cancer rises, patients are increasingly treated with nonoperative and nephron-sparing strategies, especially among the most elderly. The broader array of treatment options suggests opportunities to better personalize kidney cancer care for seniors. Published by Elsevier Inc.

Nephrectomy for benign disease in the UK: results from the British Association of Urological Surgeons nephrectomy database.

PubMed

Zelhof, Bachar; McIntyre, Iain G; Fowler, Sarah M; Napier-Hemy, Richard D; Burke, Daniel M; Grey, Ben R

2016-01-01

To summarize the practice of UK urologists with regard to nephrectomy for benign disease, documenting the indications, procedural techniques and outcomes. All patients undergoing nephrectomy for a benign condition in 2012 were identified from the British Association of Urological Surgeons (BAUS) nephrectomy database. Recorded variables included the technique of surgery, the type of minimally invasive procedure, operating time, blood loss, transfusion rate, conversion rate, intra- and postoperative complications and mortality rate. Cases were also sub-analysed according to their pathologies to determine the differences in complication rate between stone disease, pyelonephritis, non-functioning kidney and other benign lesions. To contextualize procedural complexity, the simple nephrectomy data were compared with those obtained from the BAUS stage T1 radical nephrectomy audit. A total of 1 093 nephrectomies were performed (537 non-functioning kidneys, 142 stone disease, 129 nephrectomies secondary to pyelonephritis and 285 cases with other benign conditions). Of these, 76% were performed laparoscopically. Blood loss >500 mL was noted in 74 cases with a 4.8% blood transfusion rate. The intra- and postoperative complication rates were 5.2 and 11.9%, respectively. Of the 847 minimally invasive procedures, the conversion rate was 5.9%. Patients with stone disease have the highest intra- and postoperative complications (9.9 and 23.9%, respectively) compared with other benign pathologies. The total number of T1 radical nephrectomies performed was 1 095. In comparison with T1 radical nephrectomy, simple nephrectomy carries an increased risk of conversion to an open procedure (1.8 times), a higher rate of blood transfusion (4.8 vs 2.8%), and a higher risk of intra- and postoperative complications (5.2 vs 3.7% and 11.9 vs 10%, respectively). The present study reports the largest series of nephrectomies performed for benign disease and the resultant data now support the bespoke preoperative counselling of patients. Furthermore, it confirms the commonly held view that simple nephrectomy can be more difficult than its radical counterpart. The authors suggest that the term 'simple nephrectomy' is changed to 'benign nephrectomy'. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

The Effect of Cone Opsin Mutations on Retinal Structure and the Integrity of the Photoreceptor Mosaic

PubMed Central

Carroll, Joseph; Dubra, Alfredo; Gardner, Jessica C.; Mizrahi-Meissonnier, Liliana; Cooper, Robert F.; Dubis, Adam M.; Nordgren, Rick; Genead, Mohamed; Connor, Thomas B.; Stepien, Kimberly E.; Sharon, Dror; Hunt, David M.; Banin, Eyal; Hardcastle, Alison J.; Moore, Anthony T.; Williams, David R.; Fishman, Gerald; Neitz, Jay; Neitz, Maureen; Michaelides, Michel

2012-01-01

Purpose. To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations. Methods. Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array. Results. While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with “L/M interchange” mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (∼25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic. Conclusions. The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy. PMID:23139274

Light entrainment of the murine intraocular pressure circadian rhythm utilizes non-local mechanisms.

PubMed

Tsuchiya, Shunsuke; Buhr, Ethan D; Higashide, Tomomi; Sugiyama, Kazuhisa; Van Gelder, Russell N

2017-01-01

Intraocular pressure (IOP) is known to have a strong circadian rhythm, yet how light/dark cycles entrain this rhythm is unknown. The purpose of this study was to assess whether, like the retina, the mammalian ciliary body and IOP clocks have an intrinsic ability to entrain to light/dark cycles. Iris-ciliary body complexes were obtained from period2:luciferase (PER2::LUC) mice and cultured to measure bioluminescence rhythmicity. Pairs of the iris-ciliary body complex were exposed to antiphasic 9:15 h light/dark cycle in vitro. After 4 days of exposure to light/dark cycles, bioluminescence was recorded to establish their circadian phases. In addition, pairs of the iris-ciliary body complex co-cultured with the retinas or corneas of wild-type mice were also investigated. The IOP circadian changes of free-running Opn4-/-;rd1/rd1 mice whose behavior was antiphasic to wild-type were measured by a rebound tonometry, and compared with wild-type mice. Opn3, Opn4, and Opn5 mRNA expression in the iris-ciliary body were analyzed using RT-PCR. The iris/ciliary body complex expressed Opn3, Opn4, and Opn5 mRNA; however, unlike in retina and cornea, neither the iris-CB complex nor the co-cultured complex was directly entrained by light-dark cycle in vitro. The diurnal IOP change of Opn4-/-;rd1/rd1 mice showed an antiphasic pattern to wild-type mice and their rhythms followed the whole-animal behavioral rhythm. Despite expressing mRNA for several non-visual opsins, circadian rhythms of the iris-ciliary body complex of mice do not entrain directly to light-dark cycles ex vivo. Unlike retina, the iris/ciliary body clocks of blind mice remain synchronized to the organismal behavioral rhythm rather than local light-dark cycles. These results suggest that IOP rhythm entrainment is mediated by a systemic rather than local signal in mice.

Light entrainment of the murine intraocular pressure circadian rhythm utilizes non-local mechanisms

PubMed Central

Tsuchiya, Shunsuke; Buhr, Ethan D.; Higashide, Tomomi; Sugiyama, Kazuhisa

2017-01-01

Purpose Intraocular pressure (IOP) is known to have a strong circadian rhythm, yet how light/dark cycles entrain this rhythm is unknown. The purpose of this study was to assess whether, like the retina, the mammalian ciliary body and IOP clocks have an intrinsic ability to entrain to light/dark cycles. Methods Iris-ciliary body complexes were obtained from period2:luciferase (PER2::LUC) mice and cultured to measure bioluminescence rhythmicity. Pairs of the iris-ciliary body complex were exposed to antiphasic 9:15 h light/dark cycle in vitro. After 4 days of exposure to light/dark cycles, bioluminescence was recorded to establish their circadian phases. In addition, pairs of the iris-ciliary body complex co-cultured with the retinas or corneas of wild-type mice were also investigated. The IOP circadian changes of free-running Opn4-/-;rd1/rd1 mice whose behavior was antiphasic to wild-type were measured by a rebound tonometry, and compared with wild-type mice. Opn3, Opn4, and Opn5 mRNA expression in the iris-ciliary body were analyzed using RT-PCR. Results The iris/ciliary body complex expressed Opn3, Opn4, and Opn5 mRNA; however, unlike in retina and cornea, neither the iris-CB complex nor the co-cultured complex was directly entrained by light-dark cycle in vitro. The diurnal IOP change of Opn4-/-;rd1/rd1 mice showed an antiphasic pattern to wild-type mice and their rhythms followed the whole-animal behavioral rhythm. Conclusions Despite expressing mRNA for several non-visual opsins, circadian rhythms of the iris-ciliary body complex of mice do not entrain directly to light-dark cycles ex vivo. Unlike retina, the iris/ciliary body clocks of blind mice remain synchronized to the organismal behavioral rhythm rather than local light-dark cycles. These results suggest that IOP rhythm entrainment is mediated by a systemic rather than local signal in mice. PMID:28934261

Innate Immunity Dysregulation in Myelodysplastic Syndromes

DTIC Science & Technology

2015-12-01

application of TLR2 antibody (OPN305) in patients with low-risk MDS 15. SUBJECT TERMS TLR2, lentivirus, CD34+ cells, colony formation, hematopoiesis , OPN305...with MDS. KEYWORDS TLR2, lentivirus, CD34+ cells, colony formation, hematopoiesis , OPN305 OVERALL PROJECT SUMMARY Year #1 Work and Achievement 1...fate of normal bone marrow HSPCs, suggesting that in vivo studies are needed to better evaluate the impact of TLR2 signaling in hematopoiesis . Our

Evaluation of FloSeal as a Potential Intracavitary Hemostatic Agent

DTIC Science & Technology

2006-02-01

Laws ER Jr. Use of FloSeal hemostatic sealant in transsphenoidal pituitary surgery : technical note. Neurosurgery. 2002;51:513–516. 14. Kheirabadi BS...of death in com- bat and civilian trauma. When surgery is unavailable, one potential solution to such hemorrhage might be the introduction of an agent...situations, including venous and arterial vascular surgery ,7,9 cardiac valve replacement or cardiopulmonary bypass grafting,6 partial nephrectomies,10

The future of partial nephrectomy.

PubMed

Malthouse, Theo; Kasivisvanathan, Veeru; Raison, Nicholas; Lam, Wayne; Challacombe, Ben

2016-12-01

Innovation in recent times has accelerated due to factors such as the globalization of communication; but there are also more barriers/safeguards in place than ever before as we strive to streamline this process. From the first planned partial nephrectomy completed in 1887, it took over a century to become recommended practice for small renal tumours. At present, identified areas for improvement/innovation are 1) to preserve renal parenchyma, 2) to optimise pre-operative eGFR and 3) to reduce global warm ischaemia time. All 3 of these, are statistically significant predictors of post-operative renal function. Urologists, have a proud history of embracing innovation & have experimented with different clamping techniques of the renal vasculature, image guidance in robotics, renal hypothermia, lasers and new robots under development. The DaVinci model may soon no longer have a monopoly on this market, as it loses its stranglehold with novel technology emerging including added features, such as haptic feedback with reduced costs. As ever, our predictions of the future may well fall wide of the mark, but in order to progress, one must open the mind to the possibilities that already exist, as evolution of existing technology often appears to be a revolution in hindsight. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

[Ablative treatments in localized renal cancer: literature review for 2014].

PubMed

Chodez, M; Fiard, G; Arnoux, V; Descotes, J-L; Long, J-A

2015-07-01

To focus on indications and results of ablative treatments (cyoablation, radiofrequency) for small renal masses, a bibliographic research was conducted in MedLine database using terms of "ablative treatment", "cryotherapy", "radiofrequency", "kidney cancer", "renal cell carcinoma". Sixty-four articles were selected. Carcinologic outcomes seem to be better with cryoablation than with radiofrequency. Available results have to be balanced according to surgical approach, teams' experience and duration of follow-up. Tumour's size and central localization are the main factors of failure. The size of 3cm is the most generally validated. Hospital stay and complications seem to be better with ablative therapies than with surgical approach, especially with percutaneous approach. The renal function preservation appears to be better with ablative therapies. It could be an interesting alternative to partial nephrectomy for small masses, in particular for fragile patients or in particular indications (multifocal tumors, in case of solitary kidney or transplanted kidney). The indications in elderly people must be proposed with care after the comorbidities have been evaluated. Indications of ablative treatment for small renal masses improve, but the gold standard treatment remains partial nephrectomy and indications must be individually discussed. Other ablative treatments are under-development, needing further studies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Intra-operative ultrasound-based augmented reality guidance for laparoscopic surgery.

PubMed

Singla, Rohit; Edgcumbe, Philip; Pratt, Philip; Nguan, Christopher; Rohling, Robert

2017-10-01

In laparoscopic surgery, the surgeon must operate with a limited field of view and reduced depth perception. This makes spatial understanding of critical structures difficult, such as an endophytic tumour in a partial nephrectomy. Such tumours yield a high complication rate of 47%, and excising them increases the risk of cutting into the kidney's collecting system. To overcome these challenges, an augmented reality guidance system is proposed. Using intra-operative ultrasound, a single navigation aid, and surgical instrument tracking, four augmentations of guidance information are provided during tumour excision. Qualitative and quantitative system benefits are measured in simulated robot-assisted partial nephrectomies. Robot-to-camera calibration achieved a total registration error of 1.0 ± 0.4 mm while the total system error is 2.5 ± 0.5 mm. The system significantly reduced healthy tissue excised from an average (±standard deviation) of 30.6 ± 5.5 to 17.5 ± 2.4 cm 3 ( p < 0.05) and reduced the depth from the tumor underside to cut from an average (±standard deviation) of 10.2 ± 4.1 to 3.3 ± 2.3 mm ( p < 0.05). Further evaluation is required in vivo, but the system has promising potential to reduce the amount of healthy parenchymal tissue excised.

Robot-Assisted Laparoendoscopic Single-Site Partial Nephrectomy With the Novel Da Vinci Single-Site Platform: Initial Experience

PubMed Central

Komninos, Christos; Tuliao, Patrick; Kim, Dae Keun; Choi, Young Deuk; Chung, Byung Ha

2014-01-01

Purpose To report our initial clinical cases of robotic laparoendoscopic single-site (R-LESS) partial nephrectomy (PN) performed with the use of the novel Da Vinci R-LESS platform. Materials and Methods Three patients underwent R-LESS PN from November 2013 through February 2014. Perioperative and postoperative outcomes were collected and intraoperative difficulties were noted. Results Operative time and estimated blood loss volume ranged between 100 and 110 minutes and between 50 and 500 mL, respectively. None of the patients was transfused. All cases were completed with the off-clamp technique, whereas one case required conversion to the conventional (multiport) approach because of difficulty in creating the appropriate scope for safe tumor resection. No major postoperative complications occurred, and all tumors were resected in safe margins. Length of hospital stay ranged between 3 and 7 days. The lack of EndoWrist movements, the external collisions, and the bed assistant's limited working space were noticed to be the main drawbacks of this surgical method. Conclusions Our initial experience with R-LESS PN with the novel Da Vinci platform shows that even though the procedure is feasible, it should be applied in only appropriately selected patients. However, further improvement is needed to overcome the existing limitations. PMID:24955221

Initial laboratory experience with a novel ultrasound probe for standard and single-port robotic kidney surgery: increasing console surgeon autonomy and minimizing instrument clashing.

PubMed

Yakoubi, Rachid; Autorino, Riccardo; Laydner, Humberto; Guillotreau, Julien; White, Michael A; Hillyer, Shahab; Spana, Gregory; Khanna, Rakesh; Isaac, Wahib; Haber, Georges-Pascal; Stein, Robert J; Kaouk, Jihad H

2012-06-01

The aim of this study was to evaluate a novel ultrasound probe specifically developed for robotic surgery by determining its efficiency in identifying renal tumors. The study was carried out using the Da Vinci™ surgical system in one female pig. Renal tumor targets were created by percutaneous injection of a tumor mimic mixture. Single-port and standard robotic partial nephrectomy were performed. Intraoperative ultrasound was performed using both standard laparoscopic probe and the new ProART™ Robotic probe. Probe maneuverability and ease of handling for tumor localization were recorded. The standard laparoscopic probe was guided by the assistant. Significant clashing with robotic arms was noted during the single-port procedure. The novel robotic probe was easily introduced through the assistant trocar, and held by the console surgeon using the robotic Prograsp™ with no registered clashing in the external operative field. The average time for grasping the new robotic probe was less than 10 s. Once inserted and grasped, no limitation was found in terms of instrument clashing during the single-port procedure. This novel ultrasound probe developed for robotic surgery was noted to be user-friendly when performing porcine standard and especially single-port robotic partial nephrectomy. Copyright © 2011 John Wiley & Sons, Ltd.

Robotic retroperitoneal partial nephrectomy: a step-by-step guide.

PubMed

Ghani, Khurshid R; Porter, James; Menon, Mani; Rogers, Craig

2014-08-01

To describe a step-by-step guide for successful implementation of the retroperitoneal approach to robotic partial nephrectomy (RPN) PATIENTS AND METHODS: The patient is placed in the flank position and the table fully flexed to increase the space between the 12th rib and iliac crest. Access to the retroperitoneal space is obtained using a balloon-dilating device. Ports include a 12-mm camera port, two 8-mm robotic ports and a 12-mm assistant port placed in the anterior axillary line cephalad to the anterior superior iliac spine, and 7-8 cm caudal to the ipsilateral robotic port. Positioning and port placement strategies for successful technique include: (i) Docking robot directly over the patient's head parallel to the spine; (ii) incision for camera port ≈1.9 cm (1 fingerbreadth) above the iliac crest, lateral to the triangle of Petit; (iii) Seldinger technique insertion of kidney-shaped balloon dilator into retroperitoneal space; (iv) Maximising distance between all ports; (v) Ensuring camera arm is placed in the outer part of the 'sweet spot'. The retroperitoneal approach to RPN permits direct access to the renal hilum, no need for bowel mobilisation and excellent visualisation of posteriorly located tumours. © 2014 The Authors. BJU International © 2014 BJU International.

Identification of a novel asthma susceptibility gene on chromosome 1qter and its functional evaluation.

PubMed

White, Julia H; Chiano, Mathias; Wigglesworth, Mark; Geske, Robert; Riley, John; White, Nicola; Hall, Simon; Zhu, Guohua; Maurio, Frank; Savage, Tony; Anderson, Wayne; Cordy, Joanna; Ducceschi, Melissa; Vestbo, Jorgen; Pillai, Sreekumar G

2008-07-01

Asthma is a multifactorial disease, in which the intricate interplay between genetic and environmental factors underlies the overall phenotype of the disease. Using a genome-wide scan for linkage in a population comprising of Danish families, we identified a novel linked locus on chromosome 1qter (LOD 3.6, asthma) and supporting evidence for this locus was identified for both asthma and atopic-asthma phenotypes in the GAIN (Genetics of Asthma International Network) families. The putative susceptibility gene was progressively localized to a 4.5 Mb region on chromosome 1q adjacent to the telomere, through a series of genotyping screens. Further screening using the pedigree-based association test (PBAT) identified polymorphisms in the OPN3 and CHML genes as being associated with asthma and atopic asthma after correcting for multiple comparisons. We observed that polymorphisms flanking the OPN3 and CHML genes wholly accounted for the original linkage in the Danish population and the genetic association was also confirmed in two separate studies involving the GAIN families. OPN3 and CHML are unique genes with no known function that are related to the pathophysiology of asthma. Significantly, analysis of gene expression at both RNA and protein levels, clearly demonstrated OPN3 expression in lung bronchial epithelia as well as immune cells, while CHML expression appeared minimal. Moreover, OPN3 down-regulation by siRNA knock-down in Jurkat cells suggested a possible role for OPN3 in modulation of T-cell responses. Collectively, these data suggest that OPN3 is an asthma susceptibility gene on 1qter, which unexpectedly may play a role in immune modulation.

Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer.

PubMed

Polat, Bülent; Kaiser, Philipp; Wohlleben, Gisela; Gehrke, Thomas; Scherzad, Agmal; Scheich, Matthias; Malzahn, Uwe; Fischer, Thomas; Vordermark, Dirk; Flentje, Michael

2017-01-03

In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery. Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2). A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003). Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact.

Methylglyoxal-bis-guanylhydrazone inhibits osteopontin expression and differentiation in cultured human monocytes.

PubMed

Jin, Xia; Xu, Hua; McGrath, Michael S

2018-01-01

Monocyte activation and polarization play essential roles in many chronic inflammatory diseases. An imbalance of M1 and M2 macrophage activation (pro-inflammatory and alternatively activated, respectively) is believed to be a key aspect in the etiology of these diseases, thus a therapeutic approach that regulates macrophage activation could be of broad clinical relevance. Methylglyoxal-bis-guanylhydrazone (MGBG), a regulator of polyamine metabolism, has recently been shown to be concentrated in monocytes and macrophages, and interfere with HIV integration into the DNA of these cells in vitro. RNA expression analysis of monocytes from HIV+ and control donors with or without MGBG treatment revealed the only gene to be consistently down regulated by MGBG to be osteopontin (OPN). The elevated expression of this pro-inflammatory cytokine and monocyte chemoattractant is associated with various chronic inflammatory diseases. We demonstrate that MGBG is a potent inhibitor of secreted OPN (sOPN) in cultured monocytes with 50% inhibition achieved at 0.1 μM of the drug. Furthermore, inhibition of OPN RNA transcription in monocyte cultures occurs at similar concentrations of the drug. During differentiation of monocytes into macrophages in vitro, monocytes express cell surface CD16 and the cells undergo limited DNA synthesis as measured by uptake of BrdU. MGBG inhibited both activities at similar doses to those regulating OPN expression. In addition, monocyte treatment with MGBG inhibited differentiation into both M1 and M2 classes of macrophages at non-toxic doses. The inhibition of differentiation and anti-OPN effects of MGBG were specific for monocytes in that differentiated macrophages were nearly resistant to MGBG activities. Thus MGBG may have potential therapeutic utility in reducing or normalizing OPN levels and regulating monocyte activation in diseases that involve chronic inflammation.

Cooperation of phosphates and carboxylates controls calcium oxalate crystallization in ultrafiltered urine.

PubMed

Grohe, Bernd; Chan, Brian P H; Sørensen, Esben S; Lajoie, Gilles; Goldberg, Harvey A; Hunter, Graeme K

2011-10-01

Osteopontin (OPN) is one of a group of proteins found in urine that are believed to limit the formation of kidney stones. In the present study, we investigate the roles of phosphate and carboxylate groups in the OPN-mediated modulation of calcium oxalate (CaOx), the principal mineral phase found in kidney stones. To this end, crystallization was induced by addition of CaOx solution to ultrafiltered human urine containing either human kidney OPN (kOPN; 7 consecutive carboxylates, 8 phosphates) or synthesized peptides corresponding to residues 65-80 (pSHDHMDDDDDDDDDGD; pOPAR) or 220-235 (pSHEpSTEQSDAIDpSAEK; P3) of rat bone OPN. Sequence 65-80 was also synthesized without the phosphate group (OPAR). Effects on calcium oxalate monohydrate (COM) and dihydrate (COD) formation were studied by scanning electron microscopy. We found that controls form large, partly intergrown COM platelets; COD was never observed. Adding any of the polyelectrolytes was sufficient to prevent intergrowth of COM platelets entirely, inhibiting formation of these platelets strongly, and inducing formation of the COD phase. Strongest effects on COM formation were found for pOPAR and OPAR followed by kOPN and then P3, showing that acidity and hydrophilicity are crucial in polyelectrolyte-affected COM crystallization. At higher concentrations, OPAR also inhibited COD formation, while P3, kOPN and, in particular, pOPAR promoted COD, a difference explainable by the variations of carboxylate and phosphate groups present in the molecules. Thus, we conclude that carboxylate groups play a primary role in inhibiting COM formation, but phosphate and carboxylate groups are both important in initiating and promoting COD formation.

Comparative analysis of gene expression profiles of OPN signaling pathway in four kinds of liver diseases.

PubMed

Wang, Gaiping; Chen, Shasha; Zhao, Congcong; Li, Xiaofang; Zhao, Weiming; Yang, Jing; Chang, Cuifang; Xu, Cunshuan

2016-09-01

To explore the relevance of OPN signalling pathway to the occurrence and development of nonalcoholic fatty liver disease (NAFLD), liver cirrhosis (LC), hepatic cancer (HC) and acute hepatic failure (AHF) at transcriptional level, Rat Genome 230 2.0 Array was used to detect expression profiles of OPN signalling pathway-related genes in four kinds of liver diseases. The results showed that 23, 33, 59 and 74 genes were significantly changed in the above four kinds of liver diseases, respectively. H-clustering analysis showed that the expression profiles of OPN signalling-related genes were notably different in four kinds of liver diseases. Subsequently, a total of above-mentioned 147 genes were categorized into four clusters by k-means according to the similarity of gene expression, and expression analysis systematic explorer (EASE) functional enrichment analysis revealed that OPN signalling pathway-related genes were involved in cell adhesion and migration, cell proliferation, apoptosis, stress and inflammatory reaction, etc. Finally, ingenuity pathway analysis (IPA) software was used to predict the functions of OPN signalling-related genes, and the results indicated that the activities of ROS production, cell adhesion and migration, cell proliferation were remarkably increased, while that of apoptosis, stress and inflammatory reaction were reduced in four kinds of liver diseases. In summary, the above physiological activities changed more obviously in LC, HC and AHF than in NAFLD.

Multifunctional role of osteopontin in directing intrafibrillar mineralization of collagen and activation of osteoclasts

PubMed Central

Rodriguez, Douglas E.; Thula-Mata, Taili; Toro, Edgardo J.; Yeh, Ya-Wen; Holt, Carl; Holliday, L. Shannon; Gower, Laurie B.

2013-01-01

Mineralized collagen composites are of interest because they have the potential to provide a bone-like scaffold that stimulates the natural processes of resorption and remodeling. Working toward this goal, our group has previously shown that the nanostructure of bone can be reproduced using a polymer-induced liquid-precursor (PILP) process, which enables intrafibrillar mineralization of collagen with hydroxyapatite (HA) to be achieved. This prior work used polyaspartic acid (pASP), a simple mimic for acidic non-collagenous proteins (NCPs), to generate nanodroplets/nanoparticles of an amorphous mineral precursor which can infiltrate the interstices of type-I collagen fibrils. In this study we show that osteopontin (OPN) can similarly serve as a process-directing agent for the intrafibrillar mineralization of collagen, even though OPN is generally considered a mineralization inhibitor. We also found that inclusion of OPN in the mineralization process promotes the interaction of mouse marrow-derived osteoclasts with PILP-remineralized bone that was previously demineralized, as measured by actin ring formation. While osteoclast activation occurred when pASP was used as the process-directing agent, using OPN resulted in a dramatic effect on osteoclast activation, presumably because of the inherent arginine-glycine-aspartate acid (RGD) ligands of OPN. By capitalizing on the multifunctionality of OPN, these studies may lead the way to producing biomimetic bone substitutes with the capability of tailorable bioresorption rates. PMID:24140612

Hybrids of a Genetically Engineered Antibody and a Carbon Nanotube Transistor for Detection of Prostate Cancer Biomarkers

PubMed Central

Lerner, Mitchell B.; D’Souza, Jimson; Pazina, Tatiana; Dailey, Jennifer; Goldsmith, Brett R.; Robinson, Matthew K.; Johnson, A.T. Charlie

2012-01-01

We developed a novel detection method for osteopontin (OPN), a new biomarker for prostate cancer, by attaching a genetically engineered single chain variable fragment (scFv) protein with high binding affinity for OPN to a carbon nanotube field-effect transistor (NTFET). Chemical functionalization using diazonium salts is used to covalently attach scFv to NT-FETs, as confirmed by atomic force microscopy, while preserving the activity of the biological binding site for OPN. Electron transport measurements indicate that functionalized NT-FET may be used to detect the binding of OPN to the complementary scFv protein. A concentration-dependent increase in the source-drain current is observed in the regime of clinical significance, with a detection limit of approximately 30 fM. The scFv-NT hybrid devices exhibit selectivity for OPN over other control proteins. These devices respond to the presence of OPN in a background of concentrated bovine serum albumin, without loss of signal. Based on these observations, the detection mechanism is attributed to changes in scattering at scFv protein-occupied defect sites on the carbon nanotube sidewall. The functionalization procedure described here is expected to be generalizable to any antibody containing an accessible amine group, and to result in biosensors appropriate for detection of corresponding complementary proteins at fM concentrations. PMID:22575126

Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells.

PubMed

Guidi, Novella; Sacma, Mehmet; Ständker, Ludger; Soller, Karin; Marka, Gina; Eiwen, Karina; Weiss, Johannes M; Kirchhoff, Frank; Weil, Tanja; Cancelas, Jose A; Florian, Maria Carolina; Geiger, Hartmut

2017-04-03

Upon aging, hematopoietic stem cells (HSCs) undergo changes in function and structure, including skewing to myeloid lineages, lower reconstitution potential and loss of protein polarity. While stem cell intrinsic mechanisms are known to contribute to HSC aging, little is known on whether age-related changes in the bone marrow niche regulate HSC aging. Upon aging, the expression of osteopontin (OPN) in the murine bone marrow stroma is reduced. Exposure of young HSCs to an OPN knockout niche results in a decrease in engraftment, an increase in long-term HSC frequency and loss of stem cell polarity. Exposure of aged HSCs to thrombin-cleaved OPN attenuates aging of old HSCs, resulting in increased engraftment, decreased HSC frequency, increased stem cell polarity and a restored balance of lymphoid and myeloid cells in peripheral blood. Thus, our data suggest a critical role for reduced stroma-derived OPN for HSC aging and identify thrombin-cleaved OPN as a novel niche informed therapeutic approach for ameliorating HSC phenotypes associated with aging. © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotype

PubMed Central

Capote, Joana; Martinez, Leonel; Vetrone, Sylvia; Barton, Elisabeth R.; Sweeney, H. Lee; Miceli, M. Carrie

2016-01-01

In the degenerative disease Duchenne muscular dystrophy, inflammatory cells enter muscles in response to repetitive muscle damage. Immune factors are required for muscle regeneration, but chronic inflammation creates a profibrotic milieu that exacerbates disease progression. Osteopontin (OPN) is an immunomodulator highly expressed in dystrophic muscles. Ablation of OPN correlates with reduced fibrosis and improved muscle strength as well as reduced natural killer T (NKT) cell counts. Here, we demonstrate that the improved dystrophic phenotype observed with OPN ablation does not result from reductions in NKT cells. OPN ablation skews macrophage polarization toward a pro-regenerative phenotype by reducing M1 and M2a and increasing M2c subsets. These changes are associated with increased expression of pro-regenerative factors insulin-like growth factor 1, leukemia inhibitory factor, and urokinase-type plasminogen activator. Furthermore, altered macrophage polarization correlated with increases in muscle weight and muscle fiber diameter, resulting in long-term improvements in muscle strength and function in mdx mice. These findings suggest that OPN ablation promotes muscle repair via macrophage secretion of pro-myogenic growth factors. PMID:27091452

Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy.

PubMed

Machado, Christiano; Malheiros, Denise Maria Avancini Costa; Adamy, Ari; Santos, Luiz Sergio; Silva Filho, Agenor Ferreira da; Nahas, William Carlos; Lemos, Francine Brambate Carvalhinho

2013-04-01

Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage. This study investigated whether laparoscopic donor nephrectomy modified the protective response of renal tissue during kidney transplantation. Patients undergoing live renal transplantation were prospectively analyzed and divided into two groups based on the donor nephrectomy approach used: 1) the control group, recipients of open donor nephrectomy (n = 29), and 2) the study group, recipients of laparoscopic donor nephrectomy (n = 26). Graft biopsies were obtained at two time points: T-1 = after warm ischemia time and T+1 = 45 minutes after kidney reperfusion. The samples were analyzed by immunohistochemistry for the Bcl-2 and HO-1 proteins and by real-time polymerase chain reaction for the mRNA expression of Bcl-2, HO-1 and vascular endothelial growth factor. The area under the curve for creatinine and delayed graft function were similar in both the laparoscopic and open groups. There was no difference in the protective gene expression between the laparoscopic donor nephrectomy and open donor nephrectomy groups. The protein expression of HO-1 and Bcl-2 were similar between the open and laparoscopic groups. Furthermore, the gene expression of B-cell lymphoma 2 correlated with the warm ischemia time in the open group (p = 0.047) and that of vascular endothelial growth factor with the area under the curve for creatinine in the laparoscopic group (p = 0.01). The postoperative renal function and protective factor expression were similar between laparoscopic donor nephrectomy and open donor nephrectomy. These findings ensure laparoscopic donor nephrectomy utilization in renal transplantation.

Retroperitoneal access for robotic renal surgery.

PubMed

Anderson, Barrett G; Wright, Alec J; Potretzke, Aaron M; Figenshau, R Sherburne

2018-01-01

Retroperitoneal access for robotic renal surgery is an effective alternative to the commonly used transperitoneal approach. We describe our contemporary experience and technique for attaining retroperitoneal access. We outline our institutional approach to retroperitoneal access for the instruction of urologists at the beginning of the learning curve. The patient is placed in the lateral decubitus position. The first incision is made just inferior to the tip of the twelfth rib as described by Hsu, et al. After the lumbodorsal fascia is traversed, the retroperitoneal space is dilated with a round 10 millimeter AutoSutureTM (Covidien, Mansfield, MA) balloon access device. The following trocars are used: A 130 millimeter KiiR balloon trocar (Applied Medical, Rancho Santa Margarita, CA), three robotic, and one assistant. Key landmarks for the access and dissection are detailed. 177 patients underwent a retroperitoneal robotic procedure from 2007 to 2015. Procedures performed include 158 partial nephrectomies, 16 pyeloplasties, and three radical nephrectomies. The robotic fourth arm was utilized in all cases. When compared with the transperitoneal approach, the retroperitoneal approach was associated with shorter operative times and decreased length of stay (1). Selection bias and surgeon preference accounted for the higher proportion of patients who underwent partial nephrectomy off-camp via the retroperitoneal approach. Retroperitoneal robotic surgery may confer several advantages. In patients with previous abdominal surgery or intra-abdominal conditions, the retroperitoneum can be safely accessed while avoiding intraperitoneal injuries. The retroperitoneum also provides a confined space that may minimize the sequelae of potential complications including urine leak. Moreover, at our institution, retroperitoneal robotic surgery is associated with shorter operative times and a decreased length of stay when compared with the transperitoneal approach (2). In selected patients, the retroperitoneal approach is a viable alternative to the transperitoneal approach for a variety of renal procedures. Copyright® by the International Brazilian Journal of Urology.

[Osteopontin and male reproduction].

PubMed

Liu, Qian; Xie, Qing-Zhen

2012-05-01

Osteopontin (OPN) is an extracellular matrix protein with multifunctions, expressed in various tissues and body fluids, involved in various physiological and pathological processes. It is also detected in the reproductive tract of both males and females, and participates in the implantation, development and differentiation of embryos. Recent studies have indicated that OPN is closely related with male fertility and may affect sperm quality and fertilization. An insight into the functions of OPN may help to explain the mechanisms of male infertility and improve the success rate of assisted reproductive technology.

Effects of maternal subtotal nephrectomy on the development of the fetal kidney: A morphometric study.

PubMed

Kondo, Tomohiro; Kitano-Amahori, Yoko; Nagai, Hiroaki; Mino, Masaki; Takeshita, Ai; Kusakabe, Ken Takeshi; Okada, Toshiya

2015-11-01

The present study was designed to explore if maternal subtotal (5/6) nephrectomy affects the development of fetal rat kidneys using morphometric methods and examining whether there are any apoptotic changes in the fetal kidney. To generate 5/6 nephrectomized model rats, animals underwent 2/3 left nephrectomy on gestation day (GD) 5 and total right nephrectomy on GD 12. The fetal kidneys were examined on GDs 16 and 22. A significant decrease in fetal body weight resulting from maternal 5/6 nephrectomy was observed on GD 16, and a significant decrease in fetal renal weight and fetal body weight caused by maternal nephrectomy was observed on GD 22. Maternal 5/6 nephrectomy induced a significant increase in glomerular number, proximal tubular length, and total proximal tubular volume of fetuses on GD 22. Maternal 5/6 nephrectomy resulted in an increase in the number of apoptotic cells in the metanephric mesenchyme of the kidney on GD 16, and in the collecting tubules on GD 22. These findings suggest that maternal 5/6 nephrectomy stimulates the development of the fetal kidney while suppressing fetal growth. © 2015 Japanese Teratology Society.

Effects of Artesunate on the Expressions of Insulin-Like Growth Factor-1, Osteopontin and C-Telopeptides of Type II Collagen in a Rat Model of Osteoarthritis.

PubMed

Bai, Zhe; Guo, Xiao-Hui; Tang, Chi; Yue, Si-Tong; Shi, Long; Qiang, Bo

2018-01-01

The study aims to explore the effects of artesunate on insulin-like growth factor-1 (IGF-1), Osteopontin (OPN), and C-telopeptides of type II collagen (CTX-II) in serum, synovial fluid (SF), and cartilage tissues of rats with osteoarthritis (OA). OA models were established. Normal model, artesunate, and Viatril-S groups (20 rats respectively) were set. Enzyme-linked immunosorbent assay, IHC staining, and quantitative real-time polymerase chain reaction were conducted to calculate IGF-1, OPN, and CTX-II levels in serum, SF, and cartilage tissues of rats. The pathological changes in cartilage tissues were evaluated with Mankin score and Hematoxylin-Eosin staining. Compared with the normal group, the model group showed increased IGF-1 level; decreased OPN, CTX-II levels in the serum and SF; and contrary results were seen in the cartilage tissues. A gradual ascending IGF-1 level and descending OPN and CTX-II levels existed in the serum and SF in the artesunate and Viatril-S groups after 2 weeks. The model group showed the most obvious pathological changes and highest Mankin score compared with the other groups. Higher IGF-1 level and lower OPN, CTX-II levels were exhibited in the cartilage tissue in the artesunate and Viatril-S groups but not in the model group. Artesunate and Viatril-S inhibit OA development by elevating IGF-1 level and reducing OPN and CTX-II levels. © 2017 S. Karger AG, Basel.

Localized renal cell carcinoma management: an update.

PubMed

Heldwein, Flavio L; McCullough, T Casey; Souto, Carlos A V; Galiano, Marc; Barret, Eric

2008-01-01

To review the current modalities of treatment for localized renal cell carcinoma. A literature search for keywords: renal cell carcinoma, radical nephrectomy, nephron sparing surgery, minimally invasive surgery, and cryoablation was performed for the years 2000 through 2008. The most relevant publications were examined. New epidemiologic data and current treatment of renal cancer were covered. Concerning the treatment of clinically localized disease, the literature supports the standardization of partial nephrectomy and laparoscopic approaches as therapeutic options with better functional results and oncologic success comparable to standard radical resection. Promising initial results are now available for minimally invasive therapies, such as cryotherapy and radiofrequency ablation. Active surveillance has been reported with acceptable results, including for those who are poor surgical candidates. This review covers current advances in radical and conservative treatments of localized kidney cancer. The current status of nephron-sparing surgery, ablative therapies, and active surveillance based on natural history has resulted in great progress in the management of localized renal cell carcinoma.

Clinical implications of a rare renal entity: Pleomorphic Hyalinizing Angiectatic Tumor (PHAT).

PubMed

Scalici Gesolfo, Cristina; Serretta, Vincenzo; Di Maida, Fabrizio; Giannone, Giulio; Barresi, Elisabetta; Franco, Vito; Montironi, Rodolfo

2017-02-01

Pleomorphic Hyalinizing Angiectatic Tumor (PHAT) is a rare benign lesion characterized by slow growth, infiltrative behavior and high rate of local recurrences. Only one case has been described in retroperitoneum, at renal hilum, but not involving pelvis or parenchyma. Here we present the first case of PHAT arising in the renal parenchyma. A nodular lesion in right kidney lower pole was diagnosed to a 61 year old woman. The patient underwent right nephrectomy. Microscopically, the lesion showed solid and pseudo-cystic components with hemorrhagic areas characterized by aggregates of ectatic blood vessels. Pleomorphic cells were characterized by large eosinophilic cytoplasm with irregular and hyperchromatic nuclei. Immunohistochemistry was performed and the lesion was classified as a Pleomorphic Hyalinizing Angiectatic Tumor (PHAT). Due to the clinical behavior of this tumor, in spite of its benign nature, review of the surgical margins and close follow up after partial nephrectomy are mandatory. Copyright © 2016. Published by Elsevier GmbH.

Melanopsin photoreception in the eye regulates light-induced skin colour changes through the production of α-MSH in the pituitary gland.

PubMed

Bertolesi, Gabriel E; Hehr, Carrie L; McFarlane, Sarah

2015-09-01

How skin colour adjusts to circadian light/dark cycles is poorly understood. Melanopsin (Opn4) is expressed in melanophores, where in vitro studies suggest it regulates skin pigmentation through a 'primary colour response' in which light photosensitivity is translated directly into pigment movement. However, the entrainment of the circadian rhythm is regulated by a population of melanopsin-expressing retinal ganglion cells (mRGCs) in the eye. Therefore, in vivo, melanopsin may trigger a 'secondary colour response' initiated in the eye and controlled by the neuro-endocrine system. We analysed the expression of opn4m and opn4x and melanin aggregation induced by light (background adaptation) in Xenopus laevis embryos. While opn4m and opn4x are expressed at early developmental times, light-induced pigment aggregation requires the eye to become functional. Pharmacological inhibition of melanopsin suggests a model whereby mRGC activation lightens skin pigmentation via a secondary response involving negative regulation of alpha-melanocyte-stimulating hormone (α-MSH) secretion by the pituitary. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Robot-assisted Partial Nephrectomy: 5-yr Oncological Outcomes at a Single European Tertiary Cancer Center.

PubMed

Vartolomei, Mihai Dorin; Matei, Deliu Victor; Renne, Giuseppe; Tringali, Valeria Maria; Crisan, Nicolae; Musi, Gennaro; Mistretta, Francesco Alessandro; Russo, Andrea; Cozzi, Gabriele; Cordima, Giovani; Luzzago, Stefano; Cioffi, Antonio; Di Trapani, Ettore; Catellani, Michele; Delor, Maurizio; Bottero, Danilo; Imbimbo, Ciro; Mirone, Vincenzo; Ferro, Matteo; de Cobelli, Ottavio

2017-10-27

Nowadays, there is a debate about which surgical treatment should be best for clinical T1 renal tumors. If the oncological outcomes are considered, there are many open and laparoscopic series published. As far as robotic series are concerned, only a few of them report 5-yr oncological outcomes. The aim of this study was to analyze robot-assisted partial nephrectomy (RAPN) midterm oncological outcomes achieved in a tertiary robotic reference center. Between April 2009 and September 2013, 123 consecutive patients with clinical T1-stage renal masses underwent RAPN in our tertiary cancer center. Inclusion criteria were as follows: pathologically confirmed renal cell carcinomas (RCCs) and follow-up for >12 mo. Eighteen patients were excluded due to follow-up of <12 mo and 15 due to benign final pathology. Median follow-up was 59 mo (interquartile range 44-73 mo). Patients were followed according to guideline recommendations and institutional protocol. Outcomes were measured by time to disease progression, overall survival, or time to cancer-specific death. Kaplan-Meier method was used to estimate survival; log-rank tests were applied for pair-wise comparison of survival. From the 90 patients included, 66 (73.3%) had T1a, 12 (13.3%) T1b, three (3.3%) T2a, and nine (10%) T3a tumors. Predominant histological type was clear cell carcinoma: 67 (74.5%). Fuhrmann grade 1 and 2 was found in 73.3% of all malignant tumors. Two patients (2.2%) had positive surgical margins, and complication rate was 17.8%. Relapse rate was 7.7%, including two cases (2.2%) of local recurrences and five (5.5%) distant metastasis. Five-year disease-free survival was 90.9%, 5-yr cancer-specific survival was 97.5%, and 5-yr overall survival was 95.1%. Midterm oncological outcomes after RAPN for localized RCCs (predominantly T1a tumors of low anatomic complexity) were shown to be good, adding significant evidence to support the oncological efficacy and safety of RAPN for the treatment of this type of tumors. Robot-assisted partial nephrectomy seems to be the most promising minimally invasive approach in the treatment of renal masses suitable for organ-sparing surgery as midterm (5 yr) oncological outcomes are excellent. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy

PubMed Central

Machado, Christiano; Malheiros, Denise Maria Avancini Costa; Adamy, Ari; Santos, Luiz Sergio; da Silva Filho, Agenor Ferreira; Nahas, William Carlos; Lemos, Francine Brambate Carvalhinho

2013-01-01

OBJECTIVE: Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage. This study investigated whether laparoscopic donor nephrectomy modified the protective response of renal tissue during kidney transplantation. METHODS: Patients undergoing live renal transplantation were prospectively analyzed and divided into two groups based on the donor nephrectomy approach used: 1) the control group, recipients of open donor nephrectomy (n = 29), and 2) the study group, recipients of laparoscopic donor nephrectomy (n = 26). Graft biopsies were obtained at two time points: T-1 = after warm ischemia time and T+1 = 45 minutes after kidney reperfusion. The samples were analyzed by immunohistochemistry for the Bcl-2 and HO-1 proteins and by real-time polymerase chain reaction for the mRNA expression of Bcl-2, HO-1 and vascular endothelial growth factor. RESULTS: The area under the curve for creatinine and delayed graft function were similar in both the laparoscopic and open groups. There was no difference in the protective gene expression between the laparoscopic donor nephrectomy and open donor nephrectomy groups. The protein expression of HO-1 and Bcl-2 were similar between the open and laparoscopic groups. Furthermore, the gene expression of B-cell lymphoma 2 correlated with the warm ischemia time in the open group (p = 0.047) and that of vascular endothelial growth factor with the area under the curve for creatinine in the laparoscopic group (p = 0.01). CONCLUSION: The postoperative renal function and protective factor expression were similar between laparoscopic donor nephrectomy and open donor nephrectomy. These findings ensure laparoscopic donor nephrectomy utilization in renal transplantation. PMID:23778338

Impact of Orbit Position Errors on Future Satellite Gravity Models

NASA Astrophysics Data System (ADS)

Encarnacao, J.; Ditmar, P.; Klees, R.

2015-12-01

We present the results of a study of the impact of orbit positioning noise (OPN) caused by incomplete knowledge of the Earth's gravity field on gravity models estimated from satellite gravity data. The OPN is simulated as the difference between two sets of orbits integrated on the basis of different static gravity field models. The OPN is propagated into ll-SST data, here computed as averaged inter-satellite accelerations projected onto the Line of Sight (LoS) vector between the two satellites. We consider the cartwheel formation (CF), pendulum formation (PF), and trailing formation (TF) as they produce a different dominant orientation of the LoS vector. Given the polar orbits of the formations, the LoS vector is mainly aligned with the North-South direction in the TF, with the East-West direction in the PF (i.e. no along-track offset), and contains a radial component in the CF. An analytical analysis predicts that the CF suffers from a very high sensitivity to the OPN. This is a fundamental characteristic of this formation, which results from the amplification of this noise by diagonal components of the gravity gradient tensor (defined in the local frame) during the propagation into satellite gravity data. In contrast, the OPN in the data from PF and TF is only scaled by off-diagonal gravity gradient components, which are much smaller than the diagonal tensor components. A numerical analysis shows that the effect of the OPN is similar in the data collected by the TF and the PF. The amplification of the OPN errors for the CF leads to errors in the gravity model that are three orders of magnitude larger than those in case of the PF. This means that any implementation of the CF will most likely produce data with relatively low quality since this error dominates the error budget, especially at low frequencies. This is particularly critical for future gravimetric missions that will be equipped with highly accurate ranging sensors.

Wound infections after transplant nephrectomy.

PubMed

Kohlberg, W I; Tellis, V A; Bhat, D J; Driscoll, B; Veith, F J

1980-05-01

Wound infections after transplant nephrectomy were analyzed retrospectively. When prophylactic antibiotics were not used, 20% of the closed nephrectomy wounds became infected. Eighty-one percent of the infections were due to staphylococcal organisms. Wounds containing a preexisting focus of infection or those reoperated on more than once within a month prior to nephrectomy are at such high risk for infection that these wounds should be left open for secondary healing. With the use of prophylactic cefazolin sodium, in the immediate preoperative and postoperative period, no wound infections have occurred in 18 closed transplant nephrectomy wounds.

Use of the holmium:YAG laser in urology.

PubMed

Johnson, D E; Cromeens, D M; Price, R E

1992-01-01

The tissue effects of a holmium:YAG (Ho:YAG) laser operating at a wavelength of 2.1 mu with a maximum power of 15 watts (W) and 10 different energy-pulse settings was systematically evaluated on kidney, bladder, prostate, ureteral, and vasal tissue in the dog. In addition, various urologic surgical procedures (partial nephrectomy, transurethral laser incision of the prostate, and laser-assisted vasovasostomy) were performed in the dog, and a laparoscopic pelvic lymph node dissection was carried out in a pig. Although the Ho:YAG laser has a strong affinity for water, precise tissue ablation was achieved in both the contact and non-contact mode when used endoscopically in a fluid medium to ablate prostatic and vesical tissue. Using the usual parameters for tissue destruction (blanching without charring), the depth of thermal injury in the bladder and ureter was kept superficial. In performing partial nephrectomies, a 2-fold reduction in the zone of coagulative necrosis was demonstrated compared to the use of the continuous wave Neodymium:YAG laser (Nd:YAG). When used through the laparoscope, the Ho:YAG laser provided precise cutting and, combined with electrocautery, allowed the dissection to proceed quickly and smoothly. Hemostatic control was adequate in all surgical procedures. Although the results of these investigations are preliminary, our initial experience with the Ho:YAG laser has been favorable and warrants further investigations.

Renal Arterial Pseudoaneurysm and Renal Arteriovenous Fistula Following Partial Nephrectomy.

PubMed

Chen, Jinchao; Yang, Min; Wu, Pengjie; Li, Teng; Ning, Xianghui; Peng, Shuanghe; Wang, Jiangyi; Qi, Nienie; Gong, Kan

2018-01-01

Renal arterial pseudoaneurysm (RAP) and renal arteriovenous fistula (RAVF) are rare but can cause fatal bleeding. A retrospective review was conducted for patients undergoing partial nephrectomy (PN) in our department. The clinical features and treatment methods were analysed, and the relationships between RAP/RAVF and the surgical methods and R.E.N.A.L. score were investigated. Eleven patients were diagnosed with RAP/RAVF (9 with RAP and 2 with RAVF). The incidence of RAP/RAVF after laparoscopic PN showed no significant difference compared to that after open PN (p = 0.47). A low R.E.N.A.L. score was present in 6 patients, while an intermediate/high score was present in the other 5 patients. The major clinical manifestations included haematuria and haemorrhagic shock, and the median time of occurrence was 8 days after the operation. Six patients underwent an ultrasound examination. Of the 4 patients who underwent enhanced CT, 2 patients were diagnosed with RAP. All 11 patients were diagnosed by renal angiography and were cured after super-selective arterial embolization. The serum creatinine levels before and after embolization showed no significant differences (p = 0.14). RAP/RAVF may not have any relationship with the surgical procedure or R.E.N.A.L. score. Renal angiography and super-selective arterial embolization are the preferred methods for diagnosing and treating RAP/RAVF. © 2016 S. Karger AG, Basel.

Emergent Embolization of a Very Late Detected Pseudoaneurysm at a Lower Pole Subsegmental Artery of the Kidney after Clampless Laparoscopic Partial Nephrectomy

PubMed Central

Chiancone, Francesco; Fedelini, Maurizio; Pucci, Luigi; Di Lorenzo, Domenico; Meccariello, Clemente; Fedelini, Paolo

2017-01-01

Renal artery pseudoaneurysm is a rare but life-threatening condition. Its incidence is higher after minimally invasive partial nephrectomy (PN) than after the open approach. We reported a case of a renal artery pseudoaneurysm occurred about four months after a clampless laparoscopic PN. A 49-year-old female underwent a clampless laparoscopic PN for a right renal tumor with high surgical complexity. The patient experienced an intraoperative blood loss from renal bed and the surgeons performed a deep medullary absorbable suture. Three months after surgery the patient underwent a renal ultrasonography with good results. The patient came to our emergency department 115 days after surgery with a hypovolemic shock stage 3. Her CT scan showed a pseudoaneurysm of a lower pole vessel of the right kidney. She underwent a superselective embolization of the segmental renal artery. The surgical complexity of the tumor, the anatomical relationships with the renal sinus and the deep medullary suture could be responsible for the development of the pseudoaneurysm. The authors presented an unusual case of a very late detected pseudoaneurysm of a renal vessel, suggesting that all very complex renal tumors removed with a minimally invasive technique should be followed up closely at least during the first six-months in order to early detect this major complication. PMID:28785196

Evolving practice patterns for the management of small renal masses in the USA.

PubMed

Yang, Glen; Villalta, Jacqueline D; Meng, Maxwell V; Whitson, Jared M

2012-10-01

What's known on the subject? and What does the study add? Treatment options for small renal masses include radical nephrectomy (RN), partial nephrectomy (PN), ablation, and surveillance. PN provides equivalent oncological as RN for small tumours, but long-term outcomes for ablation and surveillance are poorly defined. Due to changing techniques and technology, treatment patterns for small renal masses are rapidly developing. Prior studies had analysed utilisation trends for PN and RN to 2006, revealing a relative rise in the rate of PN. However, overall treatment trends including surveillance and ablation had not been studied using a population-based cohort. It has become increasingly clear that RN is associated with greater renal and cardiovascular deterioration than nephron-sparing treatments. Thus, it is important to understand current population-based practice patterns for the treatment of small renal masses to assess whether practitioners are adhering to ever-changing principles in this field. The present study provides up-to-date treatment trends in the USA using a large population-based cohort. To describe the changing practice patterns in the management of small renal masses, including the use of surveillance and ablative techniques. All patients in the Surveillance, Epidemiology and End Results (SEER) registry treated for renal masses of ≤7 cm in diameter, from 1998 to 2008, were included for analysis. Annual trends in the use of surveillance, ablation, partial nephrectomy (PN), and radical nephrectomy (RN) were calculated. Multinomial logistic regression was used to determine the association of demographic and clinical characteristics with treatment method. In all, 48 148 patients from 17 registry sites with a mean age of 63.4 years were included for analysis. Between 1998 and 2008, for masses of <2 cm and 2.1-4 cm, there was a dramatic increase in the proportion of patients undergoing PN (31% vs 50%, 16% vs 33%, respectively) and ablation (1% vs 11%, 2% vs 9%, respectively). In multivariable analysis, later year of diagnosis, male gender, being married, clinically localised disease, and smaller tumours were associated with increased use of PN vs RN. Later year of diagnosis, male gender, being unmarried, smaller tumour, and the presence of bilateral masses were associated with increased use of ablation and surveillance vs RN. PN is now used in half of all patients with the smallest renal masses, and its use continues to increase over time. Ablation and surveillance are less common overall, but there is increased usage over time in select populations. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.

Myopia and Late-Onset Progressive Cone Dystrophy Associate to LVAVA/MVAVA Exon 3 Interchange Haplotypes of Opsin Genes on Chromosome X.

PubMed

Orosz, Orsolya; Rajta, István; Vajas, Attila; Takács, Lili; Csutak, Adrienne; Fodor, Mariann; Kolozsvári, Bence; Resch, Miklós; Sényi, Katalin; Lesch, Balázs; Szabó, Viktória; Berta, András; Balogh, István; Losonczy, Gergely

2017-03-01

Rare interchange haplotypes in exon 3 of the OPN1LW and OPN1MW opsin genes cause X-linked myopia, color vision defect, and cone dysfunction. The severity of the disease varies on a broad scale from nonsyndromic high myopia to blue cone monochromatism. Here, we describe a new genotype-phenotype correlation attributed to rare exon 3 interchange haplotypes simultaneously present in the long- and middle-wavelength sensitive opsin genes (L- and M-opsin genes). A multigenerational family with X-linked high myopia and cone dystrophy was investigated. Affected male patients had infantile onset myopia with normal visual acuity and color vision until their forties. Visual acuity decreased thereafter, along with the development of severe protan and deutan color vision defects. A mild decrease in electroretinography response of cone photoreceptors was detected in childhood, which further deteriorated in middle-aged patients. Rods were also affected, however, to a lesser extent than cones. Clinical exome sequencing identified the LVAVA and MVAVA toxic haplotypes in the OPN1LW and OPN1MW opsin genes, respectively. Here, we show that LVAVA haplotype of the OPN1LW gene and MVAVA haplotype of the OPN1MW gene cause apparently nonsyndromic high myopia in young patients but lead to progressive cone-rod dystrophy with deuteranopia and protanopia in middle-aged patients corresponding to a previously unknown disease course. To the best of our knowledge, this is the first report on the joint effect of these toxic haplotypes in the two opsin genes on chromosome X.

Renal calcinosis and stone formation in mice lacking osteopontin, Tamm-Horsfall protein, or both.

PubMed

Mo, Lan; Liaw, Lucy; Evan, Andrew P; Sommer, Andre J; Lieske, John C; Wu, Xue-Ru

2007-12-01

Although often supersaturated with mineral salts such as calcium phosphate and calcium oxalate, normal urine possesses an innate ability to keep them from forming harmful crystals. This inhibitory activity has been attributed to the presence of urinary macromolecules, although controversies abound regarding their role, or lack thereof, in preventing renal mineralization. Here, we show that 10% of the mice lacking osteopontin (OPN) and 14.3% of the mice lacking Tamm-Horsfall protein (THP) spontaneously form interstitial deposits of calcium phosphate within the renal papillae, events never seen in wild-type mice. Lack of both proteins causes renal crystallization in 39.3% of the double-null mice. Urinalysis revealed elevated concentrations of urine phosphorus and brushite (calcium phosphate) supersaturation in THP-null and OPN/THP-double null mice, suggesting that impaired phosphorus handling may be linked to interstitial papillary calcinosis in THP- but not in OPN-null mice. In contrast, experimentally induced hyperoxaluria provokes widespread intratubular calcium oxalate crystallization and stone formation in OPN/THP-double null mice, while completely sparing the wild-type controls. Whole urine from OPN-, THP-, or double-null mice all possessed a dramatically reduced ability to inhibit the adhesion of calcium oxalate monohydrate crystals to renal epithelial cells. These data establish OPN and THP as powerful and functionally synergistic inhibitors of calcium phosphate and calcium oxalate crystallization in vivo and suggest that defects in either molecule may contribute to renal calcinosis and stone formation, an exceedingly common condition that afflicts up to 12% males and 5% females.

Validation of a Postoperative Nomogram Predicting Recurrence in Patients with Conventional Clear Cell Renal Cell Carcinoma.

PubMed

Lee, Byron H; Feifer, Andrew; Feuerstein, Michael A; Benfante, Nicole E; Kou, Lei; Yu, Changhong; Kattan, Michael W; Russo, Paul

2018-01-01

Clear cell renal cell carcinoma (RCC) continues to be the most commonly diagnosed subtype and is associated with more aggressive behavior than papillary and chromophobe RCC. Predicting disease recurrence after surgical extirpation is important for counseling and targeting those at high risk for adjuvant therapy clinical trials. To validate a postoperative nomogram predicting 5-yr recurrence-free probability (RFP) for clinically localized clear cell RCC. We identified all patients who underwent nephrectomy for clinically localized clear cell RCC from 1990 to 2009 at Memorial Sloan Kettering Cancer Center. After excluding patients with bilateral renal masses, familial RCC syndromes, and T3c or T4 tumors due to the limited number, 1642 participants were available for analysis. Partial or radical nephrectomy. Disease recurrence was defined as any new tumor after nephrectomy or kidney cancer-specific mortality, whichever occurred first. A postoperative nomogram was used to calculate the predicted 5-yr RFP, and these values were compared with the actual 5-yr RFP. Nomogram performance was evaluated by concordance index and calibration plot. Median follow-up was 39 mo (interquartile range: 14-79 mo), and disease recurrence was observed in 50 patients. The nomogram concordance index was 0.81. The calibration curve showed that the nomogram underestimated the actual 5-yr RFP. We updated the nomogram by including the entire patient population, which maintained performance and significantly improved calibration. The updated clear cell RCC postoperative nomogram performed well in the combined cohort. Underestimation of actual 5-yr RFP by the original nomogram may be due to increased surgeon experience and other unknown variables. We updated a valuable prediction tool used for assessing the disease recurrence probability after nephrectomy for clear cell renal cell carcinoma. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells.

PubMed

Liu, Lingling; Luo, Qing; Sun, Jinghui; Wang, Aoli; Shi, Yisong; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

2017-06-15

Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. Copyright © 2017 Elsevier Inc. All rights reserved.

Specific Adsorption of Osteopontin and Synthetic Polypeptides to Calcium Oxalate Monohydrate Crystals

PubMed Central

Taller, Adam; Grohe, Bernd; Rogers, Kem A.; Goldberg, Harvey A.; Hunter, Graeme K.

2007-01-01

Protein-crystal interactions are known to be important in biomineralization. To study the physicochemical basis of such interactions, we have developed a technique that combines confocal microscopy of crystals with fluorescence imaging of proteins. In this study, osteopontin (OPN), a protein abundant in urine, was labeled with the fluorescent dye AlexaFluor-488 and added to crystals of calcium oxalate monohydrate (COM), the major constituent of kidney stones. In five to seven optical sections along the z axis, scanning confocal microscopy was used to visualize COM crystals and fluorescence imaging to map OPN adsorbed to the crystals. To quantify the relative adsorption to different crystal faces, fluorescence intensity was measured around the perimeter of the crystal in several sections. Using this method, it was shown that OPN adsorbs with high specificity to the edges between {100} and {121} faces of COM and much less so to {100}, {121}, or {010} faces. By contrast, poly-L-aspartic acid adsorbs preferentially to {121} faces, whereas poly-L-glutamic acid adsorbs to all faces approximately equally. Growth of COM in the presence of rat bone OPN results in dumbbell-shaped crystals. We hypothesize that the edge-specific adsorption of OPN may be responsible for the dumbbell morphology of COM crystals found in human urine. PMID:17496021

Influence of arginine-glycine-aspartic acid (RGD), integrins (alphaV and alpha5) and osteopontin on bovine sperm-egg binding, and fertilization in vitro.

PubMed

Gonçalves, R F; Wolinetz, C D; Killian, G J

2007-02-01

Osteopontin (OPN), a phosphoprotein containing an arginine-glycine-aspartic acid (RGD) sequence, has been identified in cow oviduct epithelium and fluid. To investigate the potential role OPN in fertilization, we evaluated the ability of RGD peptide (arginine-glycine-aspartic), RGE peptide (arginine-glycine-glutamic acid), integrins alphaV and alpha5 antibodies and OPN antibody to influence bovine in vitro sperm-egg binding and fertilization. Treatment of sperm or oocytes with the RGD peptide prior fertilization significantly decreased in vitro sperm-egg binding and fertilization compared to the non-treated controls or those treated with RGE peptide. Binding and fertilization were also significantly decreased when in vitro matured bovine oocytes or sperm were pre-incubated with integrins alphaV and alpha5 antibodies at concentration ranging from 5 to 20 microg/mL. Addition of a rabbit polyclonal IgG antibody against purified bovine milk OPN with sperm or/and oocytes decreased (P<0.05) fertilization compared to the in vitro-fertilized control. These data provided evidence that integrin ligands existed on bovine oocytes and spermatozoa that contained RGD recognition sequences, and that antibody to OPN, a protein that contains that RGD sequence, was capable of reducing sperm-egg binding and fertilization in vitro.

Genetic association analysis of Osteopontin and Matrix Gla Protein genes polymorphisms with primary knee osteoarthritis in Mexican population.

PubMed

Borgonio-Cuadra, Verónica Marusa; González-Huerta, Norma Celia; Rojas-Toledo, Emma Xochitl; Morales-Hernández, Eugenio; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; Tovilla-Zárate, Carlos Alfonso; González-Castro, Thelma Beatriz; Hernández-Díaz, Yazmín; López-Narváez, María Lilia; Miranda-Duarte, Antonio

2018-05-18

Primary osteoarthritis (OA) is a complex entity in which several loci related to different molecular pathways or classes of molecules are associated with its development as demonstrated through genetic association studies. Genes involved in bone formation and mineralization, such as osteopontin (OPN) and Matrix Gla protein (MGP), could also be related with OA. The aim of this study was to evaluate the association between the genetic variants of OPN and MGP with primary knee osteoarthritis in a Mexican population. A case-control study was conducted in 296 patients with primary knee osteoarthritis and in 354 control subjects. Study groups were assessed radiologically. The rs11730582 of OPN and rs1800802, rs1800801, and rs4236 of MGP were determined by TaqMan allele discrimination assays. The haplotypes of the polymorphisms of MGP were constructed. The association was tested through univariate and multivariate non-conditional logistic regression analyses. The polymorphisms of MGP complied with Hardy-Weinberg (HW) equilibrium. The polymorphisms of OPN and MGP were not significantly associated with primary knee osteoarthritis in the codominant, dominant, and recessive models (p > 0.05). Our study suggests that there are no associations between OPN and MGP polymorphisms with primary knee osteoarthritis in Mexican population.

Brain stem omnipause neurons and the control of combined eye-head gaze saccades in the alert cat.

PubMed

Paré, M; Guitton, D

1998-06-01

When the head is unrestrained, rapid displacements of the visual axis-gaze shifts (eye-re-space)-are made by coordinated movements of the eyes (eye-re-head) and head (head-re-space). To address the problem of the neural control of gaze shifts, we studied and contrasted the discharges of omnipause neurons (OPNs) during a variety of combined eye-head gaze shifts and head-fixed eye saccades executed by alert cats. OPNs discharged tonically during intersaccadic intervals and at a reduced level during slow perisaccadic gaze movements sometimes accompanying saccades. Their activity ceased for the duration of the saccadic gaze shifts the animal executed, either by head-fixed eye saccades alone or by combined eye-head movements. This was true for all types of gaze shifts studied: active movements to visual targets; passive movements induced by whole-body rotation or by head rotation about stationary body; and electrically evoked movements by stimulation of the caudal part of the superior colliculus (SC), a central structure for gaze control. For combined eye-head gaze shifts, the OPN pause was therefore not correlated to the eye-in-head trajectory. For instance, in active gaze movements, the end of the pause was better correlated with the gaze end than with either the eye saccade end or the time of eye counterrotation. The hypothesis that cat OPNs participate in controlling gaze shifts is supported by these results, and also by the observation that the movements of both the eyes and the head were transiently interrupted by stimulation of OPNs during gaze shifts. However, we found that the OPN pause could be dissociated from the gaze-motor-error signal producing the gaze shift. First, OPNs resumed discharging when perturbation of head motion briefly interrupted a gaze shift before its intended amplitude was attained. Second, stimulation of caudal SC sites in head-free cat elicited large head-free gaze shifts consistent with the creation of a large gaze-motor-error signal. However, stimulation of the same sites in head-fixed cat produced small "goal-directed" eye saccades, and OPNs paused only for the duration of the latter; neither a pause nor an eye movement occurred when the same stimulation was applied with the eyes at the goal location. We conclude that OPNs can be controlled by neither a simple eye control system nor an absolute gaze control system. Our data cannot be accounted for by existing models describing the control of combined eye-head gaze shifts and therefore put new constraints on future models, which will have to incorporate all the various signals that act synergistically to control gaze shifts.

Impact of transplant nephrectomy on peak PRA levels and outcome after kidney re-transplantation

PubMed Central

Tittelbach-Helmrich, Dietlind; Pisarski, Przemyslaw; Offermann, Gerd; Geyer, Marcel; Thomusch, Oliver; Hopt, Ulrich Theodor; Drognitz, Oliver

2014-01-01

AIM: To determine the impact of transplant nephrectomy on peak panel reactive antibody (PRA) levels, patient and graft survival in kidney re-transplants. METHODS: From 1969 to 2006, a total of 609 kidney re-transplantations were performed at the University of Freiburg and the Campus Benjamin Franklin of the University of Berlin. Patients with PRA levels above (5%) before first kidney transplantation were excluded from further analysis (n = 304). Patients with graft nephrectomy (n = 245, NE+) were retrospectively compared to 60 kidney re-transplants without prior graft nephrectomy (NE-). RESULTS: Peak PRA levels between the first and the second transplantation were higher in patients undergoing graft nephrectomy (P = 0.098), whereas the last PRA levels before the second kidney transplantation did not differ between the groups. Age adjusted survival for the second kidney graft, censored for death with functioning graft, were comparable in both groups. Waiting time between first and second transplantation did not influence the graft survival significantly in the group that underwent nephrectomy. In contrast, patients without nephrectomy experienced better graft survival rates when re-transplantation was performed within one year after graft loss (P = 0.033). Age adjusted patient survival rates at 1 and 5 years were 94.1% and 86.3% vs 83.1% and 75.4% group NE+ and NE-, respectively (P < 0.01). CONCLUSION: Transplant nephrectomy leads to a temporary increase in PRA levels that normalize before kidney re-transplantation. In patients without nephrectomy of a non-viable kidney graft timing of re-transplantation significantly influences graft survival after a second transplantation. Most importantly, transplant nephrectomy is associated with a significantly longer patient survival. PMID:25032103

Impact of parenchymal loss on renal function after laparoscopic partial nephrectomy under warm ischemia.

PubMed

Bagheri, Fariborz; Pusztai, Csaba; Farkas, László; Kallidonis, Panagiotis; Buzogány, István; Szabó, Zsuzsanna; Lantos, János; Imre, Marianna; Farkas, Nelli; Szántó, Árpád

2016-12-01

To elucidate the impact of renal parenchymal loss and the ischemic reperfusion injury (RI) on the renal function after laparoscopic partial nephrectomy (LPN) under warm ischemia (WI). Thirty-five patients with a single polar renal mass ≤4 cm and normal contralateral kidney underwent LPN. Transperitoneal LPN with WI using en bloc hilar occlusion was performed. The total differential renal function (T-DRF) using 99m Tc-dimercaptosuccinic acid was evaluated preoperatively and postoperatively over a period of 1 year. A special region of interest (ROI) was selected on the non-tumorous pole of the involved kidney, and was compared with the same ROI in the contralateral kidney. The latter comparison was defined as partial differential renal function (P-DRF). Any postoperative decline in the P-DRF of the operated kidney was attributed to the RI. Subtraction of the P-DRF decline from the T-DRF decline was attributed to the parenchymal loss caused by the resection of the tumor and suturing of the normal parenchyma. The mean WI time was 22 min, and the mean weight of resected specimen was 18 g. The mean postoperative eGFR declined to 87 ml/min/1.73 m 2 from its baseline mean value of 97 ml/min/1.73 m 2 (p value = 0.075). Mean postoperative T-DRF and P-DRF of the operated kidney declined by 7 and 3 %, respectively. After LPN of small renal mass, decline in renal function is primarily attributed to parenchymal loss caused by tumor resection and suturing of the normal parenchyma rather than the RI.

Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers.

PubMed

Kruger, Thomas E; Miller, Andrew H; Godwin, Andrew K; Wang, Jinxi

2014-02-01

The mechanisms underlying malignant cell metastasis to secondary sites such as bone are complex and no doubt multifactorial. Members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) family, particularly bone sialoprotein (BSP) and osteopontin (OPN), exhibit multiple activities known to promote malignant cell proliferation, detachment, invasion, and metastasis of several osteotropic cancers. The expression level of BSP and OPN is elevated in a variety of human cancers, particularly those that metastasize preferentially to the skeleton. Recent studies suggest that the "osteomimicry" of malignant cells is not only conferred by transmembrane receptors bound by BSP and OPN, but includes the "switch" in gene expression repertoire typically expressed in cells of skeletal lineage. Understanding the role of BSP and OPN in tumor progression, altered pathophysiology of bone microenvironment, and tumor metastasis to bone will likely result in development of better diagnostic approaches and therapeutic regimens for osteotropic malignant diseases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Gross intermittent hematuria after laparoscopic donor nephrectomy

PubMed Central

Gaurav, G; Santosh, K; Samiran, A; Ganesh, G

2008-01-01

Laparoscopic donor nephrectomy is a routine practice but still requires an intense level of attention to prevent complications. We report a rare case of gross hematuria in postoperative period after an uneventful laparoscopic donor nephrectomy. PMID:19547672

Is simple nephrectomy truly simple? Comparison with the radical alternative.

PubMed

Connolly, S S; O'Brien, M Frank; Kunni, I M; Phelan, E; Conroy, R; Thornhill, J A; Grainger, R

2011-03-01

The Oxford English dictionary defines the term "simple" as "easily done" and "uncomplicated". We tested the validity of this terminology in relation to open nephrectomy surgery. Retrospective review of 215 patients undergoing open, simple (n = 89) or radical (n = 126) nephrectomy in a single university-affiliated institution between 1998 and 2002. Operative time (OT), estimated blood loss (EBL), operative complications (OC) and length of stay in hospital (LOS) were analysed. Statistical analysis employed Fisher's exact test and Stata Release 8.2. Simple nephrectomy was associated with shorter OT (mean 126 vs. 144 min; p = 0.002), reduced EBL (mean 729 vs. 859 cc; p = 0.472), lower OC (9 vs. 17%; 0.087), and more brief LOS (mean 6 vs. 8 days; p < 0.001). All parameters suggest favourable outcome for the simple nephrectomy group, supporting the use of this terminology. This implies "simple" nephrectomies are truly easier to perform with less complication than their radical counterpart.

Nephron-sparing surgery across a nation - outcomes from the British Association of Urological Surgeons 2012 national partial nephrectomy audit.

PubMed

Fernando, Archie; Fowler, Sarah; O'Brien, Tim

2016-06-01

To determine the scope and outcomes of nephron-sparing surgery (NSS), i.e. partial nephrectomy, across the UK and in so doing set a realistic benchmark and identify fresh contemporary challenges in NSS. In 2012 reporting of outcomes of all types of nephrectomy became mandatory in the UK. In all, 148 surgeons in 86 centres prospectively entered data on 6 042 nephrectomies undertaken in 2012. This study is a retrospective analysis of the NSS procedures in the dataset. A total of 1 044 NSS procedures were recorded and the median (range) surgical volume was 4 (1-39) per consultant and 8 (1-59) per centre. In all, 36 surgeons and 10 centres reported on only one NSS. The indications for NSS were: elective with a tumour of ≤4.5 cm in 59%, elective with a tumour of >4.5 cm in 10%, relative in 7%, imperative in 12%, Von Hippel-Lindau in 1%, and unknown in 11%. The median (range) tumour size was 3.4 (0.8-30) cm. The technique used was minimally invasive surgery in 42%, open in 58%, with conversions in 4%. The histology results were: malignant in 80%, benign in 18%, and unknown in 2%. In patients aged <40 years 36% (36/101) had benign histology vs 17% (151/874) of those aged ≥40 years (P < 0.01). In patients with tumours of <2.5 cm 29% (69/238) had benign histology vs 14% (57/410) with tumours of 2.5-4 cm vs 8% (16/194) with tumours of ≥4 cm (P = 0.02). In patients aged <40 years with of tumours of <2.5 cm 44% (15/34) were benign. The 30-day mortality was 0.1% (1/1 044). There were major complications (Clavien-Dindo grade of ≥IIIa) in 5% (53/1 044). There was an increased risk of complications after extended elective NSS of 19% (19/101) vs elective at 12% (76/621) (relative risk [RR] 1.54; P < 0.01). Margins were recorded in 68% (709/1 044) of the patients, with positive margins identified in 7% (51/709). Positive surgical margins after NSS for pathological T3 (pT3) tumours were found in 47.8% (11/23) vs 6.1% (32/523) for pT1a, tumours (RR 5.61; P < 0.01). In all, 14% (894/6 042) of the patients underwent surgery for T1a tumours: 55% (488/894) by NSS, 42% (377/894) by radical nephrectomy (RN), and in 3% (29/894) the procedure used was unknown. Major complications after occurred in 4.9% (24/488) of NSS vs 1.3% (5/377) of RN (P < 0.01). Limitations included poor reporting of renal function data and no data on tumour complexity. In its first year, mandatory national reporting has provided several challenging contemporary insights into NSS. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting.

PubMed

Panda, Satchidananda; Sato, Trey K; Castrucci, Ana Maria; Rollag, Mark D; DeGrip, Willem J; Hogenesch, John B; Provencio, Ignacio; Kay, Steve A

2002-12-13

The master circadian oscillator in the hypothalamic suprachiasmatic nucleus is entrained to the day/night cycle by retinal photoreceptors. Melanopsin (Opn4), an opsin-based photopigment, is a primary candidate for photoreceptor-mediated entrainment. To investigate the functional role of melanopsin in light resetting of the oscillator, we generated melanopsin-null mice (Opn4-/-). These mice entrain to a light/dark cycle and do not exhibit any overt defect in circadian activity rhythms under constant darkness. However, they display severely attenuated phase resetting in response to brief pulses of monochromatic light, highlighting the critical role of melanopsin in circadian photoentrainment in mammals.

Osteopontin: Relation between Adipose Tissue and Bone Homeostasis.

PubMed

De Fusco, Carolina; Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Moscatelli, Fiorenzo; Valenzano, Anna; Esposito, Teresa; Sergio, Chieffi; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

2017-01-01

Osteopontin (OPN) is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it seems to be one of the most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis.

Modulation of the neurological and vascular complications by grape seed extract in a rat model of spinal cord ischemia-reperfusion injury by downregulation of both osteopontin and cyclooxygenase-2.

PubMed

Sakr, Hussein F; Abbas, Amr M; Bin-Jaliah, Ismaeel

2016-07-01

In this study, we investigated the effects of grape seed extract (GSE) on the expression of osteopontin (OPN) and cyclooxygenase-2 (COX-2) in a rat model of spinal cord ischemia-reperfusion injury (SC-IRI). Fifty male rats were divided into 5 groups: control (CON); control + GSE (CON + GSE) (received GSE for 28 days); sham operated (Sham); IRI; and IRI + GSE. SC-IRI was induced by clamping the aorta just above the bifurcation for 45 min, and then the clamp was released for 48 h for reperfusion. IRI + GSE group received GSE for 28 days before SC-IRI. Sensory, motor, and placing/stepping reflex assessment was performed. Prostaglandin E2 (PGE2), thiobarbituric acid reactive substances (TBARs), and total antioxidant capacity (TAC) were measured in spinal cord homogenate. Immunohistochemical examination of the spinal cord for OPN and COX-2 were carried out. SC-IRI resulted in significant increase in plasma nitrite/nitrate level and spinal cord homogenate levels of TBARs and PGE2, and OPN and COX-2 expression with significant decrease in TAC. GSE improves the sensory and motor functions through decreasing OPN and COX-2 expression with reduction of oxidative stress parameters. We conclude a neuroprotective effect of GSE in SC-IRI through downregulating COX-2 and OPN expression plus its antioxidants effects.

T-box Transcription Regulator Tbr2 Is Essential for the Formation and Maintenance of Opn4/Melanopsin-Expressing Intrinsically Photosensitive Retinal Ganglion Cells

PubMed Central

Li, Hongyan; Zhang, Zhijing; Kiyama, Takae; Panda, Satchidananda; Hattar, Samer; Ribelayga, Christophe P.; Mills, Stephen L.

2014-01-01

Opsin 4 (Opn4)/melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) play a major role in non-image-forming visual system. Although advances have been made in understanding their morphological features and functions, the molecular mechanisms that regulate their formation and survival remain unknown. Previously, we found that mouse T-box brain 2 (Tbr2) (also known as Eomes), a T-box-containing transcription factor, was expressed in a subset of newborn RGCs, suggesting that it is involved in the formation of specific RGC subtypes. In this in vivo study, we used complex mouse genetics, single-cell dye tracing, and behavioral analyses to determine whether Tbr2 regulates ipRGC formation and survival. Our results show the following: (1) Opn4 is expressed exclusively in Tbr2-positive RGCs; (2) no ipRGCs are detected when Tbr2 is genetically ablated before RGC specification; and (3) most ipRGCs are eliminated when Tbr2 is deleted in established ipRGCs. The few remaining ipRGCs display abnormal dendritic morphological features and functions. In addition, some Tbr2-expressing RGCs can activate Opn4 expression on the loss of native ipRGCs, suggesting that Tbr2-expressing RGCs may serve as a reservoir of ipRGCs to regulate the number of ipRGCs and the expression levels of Opn4. PMID:25253855

Melanopsin mediates light-dependent relaxation in blood vessels.

PubMed

Sikka, Gautam; Hussmann, G Patrick; Pandey, Deepesh; Cao, Suyi; Hori, Daijiro; Park, Jong Taek; Steppan, Jochen; Kim, Jae Hyung; Barodka, Viachaslau; Myers, Allen C; Santhanam, Lakshmi; Nyhan, Daniel; Halushka, Marc K; Koehler, Raymond C; Snyder, Solomon H; Shimoda, Larissa A; Berkowitz, Dan E

2014-12-16

Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4(-/-) mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430-460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor.

Very high-pressure dilatation for undilatable coronary lesions: indications and results with a new dedicated balloon.

PubMed

Secco, Gioel Gabrio; Ghione, Matteo; Mattesini, Alessio; Dall'Ara, Gianni; Ghilencea, Liviu; Kilickesmez, Kadriye; De Luca, Giuseppe; Fattori, Rossella; Parisi, Rosario; Marino, Paolo Nicola; Lupi, Alessandro; Foin, Nicolas; Di Mario, Carlo

2016-06-20

Calcific coronary lesions impose a rigid obstacle to optimal balloon and stent expansion and the 20 to 30 atm limit that non-compliant (NC) balloons reach can be insufficient. The aim of our study was to evaluate the safety and efficacy of a new dedicated super high-pressure NC balloon (OPN NC®; SIS Medical AG, Winterthur, Switzerland). We retrospectively evaluated a consecutive series of 91 lesions in which conventional NC balloons at maximal pressure failed to achieve an adequate post-dilatation luminal gain and were therefore treated with an OPN NC balloon up to 40 atm. Angiographic success was defined as residual angiographic diameter stenosis <30%. MLD and %DS were measured at baseline, after NC balloon, OPN NC balloon and stent implantation. Angiographic success was achieved in 84 lesions (92.3%). All of the remaining lesions received rotational atherectomy with the exception of two cases in which rotational atherectomy was not attempted because of small vessel size and excessive tortuosity. MLD and acute gain were significantly greater and %DS was significantly lower post OPN NC balloon compared with conventional NC balloon inflation (p<0.001). No coronary perforations occurred. No acute or 30-day follow-up MACE was reported. When conventional NC balloons fail, the new OPN NC dedicated high-pressure balloon provides an effective and safe alternative strategy for the dilatation of resistant coronary lesions.

Isolated renal hydatid disease: experience at the queen rania urology center, the king hussein medical center.

PubMed

Abu-Qamar, Adnan A; Aljader, Khalaf M; Habboub, Hazem

2004-01-01

In this retrospective study, we present our experience on the diagnosis and management of isolated Hydatid disease of the kidneys. Between January 1999 and January 2003, eight patients were diagnosed to have Hydatid disease of the kidney and constituted the subjects of this study. Their age ranged between 20 and 63 years age (mean 40); there were five males and three females. Loin pain was the commonest mode of presentation in these patients. Investigations performed included urine analysis, serological tests, eosinophil count and relevant radiological studies. Urine analysis showed hydatiduria in one patient, the Casoni's test was positive in two, Ghedini skin test was positive in three and eosinophilia was noted in two other patients. All patients were treated surgically using loin supracostal extra-peritoneal approach. Total nephrectomy was performed in five patients, partial nephrectomy in one while excision of the cyst was performed in two patients. Our report suggests that a combination of various investigative modalities with a high index of suspicion is necessary in establishing the correct diagnosis. Surgery remains the main option of treatment for renal hydatid disease.

Repair after nephron ablation reveals limitations of neonatal neonephrogenesis

PubMed Central

Tögel, Florian; Freedman, Benjamin S.; Iatrino, Rossella; Grinstein, Mor; Bonventre, Joseph V.

2017-01-01

The neonatal mouse kidney retains nephron progenitor cells in a nephrogenic zone for 3 days after birth. We evaluated whether de novo nephrogenesis can be induced postnatally beyond 3 days. Given the long-term implications of nephron number for kidney health, it would be useful to enhance nephrogenesis in the neonate. We induced nephron reduction by cryoinjury with or without contralateral nephrectomy during the neonatal period or after 1 week of age. There was no detectable compensatory de novo nephrogenesis, as determined by glomerular counting and lineage tracing. Contralateral nephrectomy resulted in additional adaptive healing, with little or no fibrosis, but did not also stimulate de novo nephrogenesis. In contrast, injury initiated at 1 week of age led to healing with fibrosis. Thus, despite the presence of progenitor cells and ongoing nephron maturation in the newborn mouse kidney, de novo nephrogenesis is not inducible by acute nephron reduction. This indicates that additional nephron progenitors cannot be recruited after birth despite partial renal ablation providing a reparative stimulus and suggests that nephron number in the mouse is predetermined at birth. PMID:28138555

Laparoscopic partial nephrectomy for endophytic hilar tumors: feasibility and outcomes.

PubMed

Di Pierro, G B; Tartaglia, N; Aresu, L; Polara, A; Cielo, A; Cristini, C; Grande, P; Gentile, V; Grosso, G

2014-06-01

To analyze feasibility and outcomes of laparoscopic partial nephrectomy (LPN) for endophytic hilar tumors in low-intermediate (ASA I-II) risk patients. This is a single centre retrospective study. From May 2009 to September 2011, 208 LPNs were performed at our institution. Overall 11 (5.2%) elective LPNs were for hilar tumors not visible on kidney surface. Hilar tumor was defined as a mass located in the renal hilum and in contact with a major renal vessel on preoperative imaging. Procedures were carried out by a single experienced surgeon (G.G.) via retroperitoneal approach by clamping the only main renal artery. Mean (range) age of patients was 45.3 years (38.2-64.1), tumor size 1.6 cm (1.2-2.0), warm ischemia time 24 min (19-32), operative time 140 min (110-200) and estimated blood loss 270 ml (100-750). Two collecting system injuries were observed and repaired intraoperatively. No conversion to open surgery was required. Final pathological examination revealed 10 renal cell carcinomas and 1 oncocytoma. A negative surgical margin was obtained in 10/11 (91%) patients. Renal function and serum hemoglobin were nearly unaltered pre and post-surgery. No tumor recurrence was observed at mean (range) follow-up of 34 months (15-43). In experienced hands, LPN represents a feasible, safe and effective treatment for selected patients diagnosed with endophytic hilar masses. A larger number of patients and longer follow-up are required to draw definitive conclusions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Significant impact of R.E.N.A.L. nephrometry score on changes in postoperative renal function early after robot-assisted partial nephrectomy.

PubMed

Miyake, Hideaki; Furukawa, Junya; Hinata, Nobuyuki; Muramaki, Mototsugu; Tanaka, Kazushi; Fujisawa, Masato

2015-06-01

Our objective was to evaluate the significance of the R.E.N.A.L. nephrometry score (RNS)--developed to quantitatively evaluate the complexity of renal tumors in a reproducible manner--in perioperative and renal functional outcomes following robot-assisted partial nephrectomy (RAPN). This study assessed 48 consecutive patients with renal tumors who underwent RAPN. Preoperative RNS for each patient was calculated, and its impact on several parameters associated with perioperative outcomes, including postoperative renal function, was investigated with Spearman's rank correlation test. Mean RNS in the 48 patients was 6.8; of these 48 patients, 21 (43.7%), 24 (50.0%), and three (6.3%) were classified into low-, moderate-, and high-complexity groups, respectively. The RNS was significantly correlated with resected tumor weight and postoperative changes in estimated glomerular filtration rate (eGFR) at both 1 and 4 weeks--but not age, body mass index (BMI), preoperative eGFR, operative time, warm ischemia time, estimated blood loss, postoperative complications, or eGFR-- after RAPN. No component of the RNS (R: radius; E: exophytic/endophytic properties; N: nearness of tumor to the collecting system or sinus; A: anterior/posterior; L: location relative to polar lines) alone had a significant impact on postoperative changes in eGFR at 1 and 4 weeks, whereas resected tumor weight was significantly associated with the R and E subcategories. Measurement of total RNS is useful for predicting renal functional outcomes early after RAPN.

Anatomical Relationship Between the Kidney Collecting System and the Intrarenal Arteries in the Sheep: Contribution for a New Urological Model.

PubMed

Buys-Gonçalves, Gabriela Faria; De Souza, Diogo Benchimol; Sampaio, Francisco José Barcellos; Pereira-Sampaio, Marco Aurélio

2016-04-01

Previous studies have demonstrated that the pig collecting system heals after partial nephrectomy without closure. Recently, a study in sheep showed that partial nephrectomy without closure of the collecting system resulted in urinary leakage and urinoma. The aim of this study was to present detailed anatomical findings on the intrarenal anatomy of the sheep. Forty two kidneys were used to produce tridimensional endocasts of the collecting system together with the intrarenal arteries. A renal pelvis which displayed 11-19 (mean of 16) renal recesses was present. There were no calices present. The renal artery was singular in each kidney and gave two primary branches one to the dorsal surface and one to ventral surface. Dorsal and ventral branches of the renal artery were classified based on the relationship between their branching pattern and the collecting system as: type I (cranial and caudal segmental arteries), type II (cranial, middle and caudal segmental arteries) or type III (cranial, cranial middle, caudal middle, and caudal segmental arteries). Type I was the most common branching pattern for the dorsal and ventral branches of the renal artery. The arterial supply of the caudal pole of the sheep kidney supports its use as an experimental model due to the similarity to the human kidney. However, the lack of a retropelvic artery discourages the use of the cranial pole in experiments in which the arteries are an important aspect to be considered. © 2016 Wiley Periodicals, Inc.

Comparison between magnetic anchoring and guidance system camera-assisted laparoendoscopic single-site surgery nephrectomy and conventional laparoendoscopic single-site surgery nephrectomy in a porcine model: focus on ergonomics and workload profiles.

PubMed

Han, Woong Kyu; Tan, Yung K; Olweny, Ephrem O; Yin, Gang; Liu, Zhuo-Wei; Faddegon, Stephen; Scott, Daniel J; Cadeddu, Jeffrey A

2013-04-01

To compare surgeon-assessed ergonomic and workload demands of magnetic anchoring and guidance system (MAGS) laparoendoscopic single-site surgery (LESS) nephrectomy with conventional LESS nephrectomy in a porcine model. Participants included two expert and five novice surgeons who each performed bilateral LESS nephrectomy in two nonsurvival animals using either the MAGS camera or conventional laparoscope. Task difficulty and workload demands of the surgeon and camera driver were assessed using the validated National Aeronautics and Space Administration Task Load Index (NASA-TLX) questionnaire. Surgeons were also asked to score 6 parameters on a Likert scale (range 1=low/easy to 5=high/hard): procedure-associated workload, ergonomics, technical challenge, visualization, accidental events, and instrument handling. Each step of the nephrectomy was also timed and instrument clashing was quantified. Scores for each parameter on the Likert scale were significantly lower for MAGS-LESS nephrectomy. Mean number of internal and external clashes were significantly lower for the MAGS camera (p<0.001). Mean task times for each procedure were shorter for experts than for novices, but this was not statistically significant. NASA-TLX workload ratings by the surgeon and camera driver showed that MAGS resulted in a significantly lower workload than the conventional laparoscope during LESS nephrectomy (p<0.05). The use of the MAGS camera during LESS nephrectomy lowers the task workload for both the surgeon and camera driver when compared to conventional laparoscope use. Subjectively, it appears to also improve surgeons' impressions of ergonomics and technical challenge. Pending approval for clinical use, further evaluation in the clinical setting is warranted.

Factors influencing the operating time for single-port laparoscopic radical nephrectomy: focus on the anatomy and distribution of the renal artery and vein.

PubMed

Matsumoto, Kazuhiro; Miyajima, Akira; Fukumoto, Keishiro; Komatsuda, Akari; Niwa, Naoya; Hattori, Seiya; Takeda, Toshikazu; Kikuchi, Eiji; Asanuma, Hiroshi; Oya, Mototsugu

2017-10-01

It is considered that laparoscopic single-site surgery should be performed by specially trained surgeons because of the technical difficulty in using special instruments through limited access. We investigated suitable patients for single-port laparoscopic radical nephrectomy, focusing on the anatomy and distribution of the renal artery and vein. This retrospective study was conducted in 52 consecutive patients who underwent single-port radical nephrectomy by the transperitoneal approach. In patients undergoing right nephrectomy, a 2-mm port was added for liver retraction. We retrospectively re-evaluated all of the recorded surgical videos and preoperative computed tomography images. The pneumoperitoneum time (PT) was used as an objective index of surgical difficulty. The PT was significantly shorter for right nephrectomy than left nephrectomy (94 vs. 123 min, P = 0.004). With left nephrectomy, dissection of the spleno-renal ligament to mobilize the spleen medially required additional time. Also, the left renal vein could only be divided after securing the adrenal, gonadal and lumbar veins. In patients whose renal artery was located cranial to the renal vein, PT tended to be longer than in the other patients (131 vs. 108 min, P = 0.070). In patients with a superior renal artery, the inferior renal vein invariably covered the artery and made it difficult to ligate the renal artery via the umbilical approach at the first procedure. These findings indicate that patients undergoing right nephrectomy in whom the renal artery is not located cranial to the renal vein are suitable for single-port laparoscopic radical nephrectomy. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Comparative Outcomes of Hand-assisted Laparoscopic Donor Nephrectomy Using Midline Incision or Low Transverse Incision for Hand-assisted Port Placement.

PubMed

Gwon, Jun Gyo; Jun, Heungman; Kim, Myung Gyu; Boo, Yoon Jung; Jung, Cheol Woong

2016-06-01

Hand-assisted laparoscopic donor nephrectomy is performed in many centers for donor nephrectomy. A midline incision for hand-assisted port placement is generally used but produces an unsightly scar. In this study, patients who had hand-assisted laparoscopic donor nephrectomy with low transverse incision were compared with those who received a midline incision. Our study group included patients who received hand-assisted laparoscopic donor nephrectomy from February 2012 to December 2014 at Korea University Anam Hospital. We retrospectively compared outcomes of these patients based on midline incision (45 patients) versus low transverse incision (17 patients). Risk factors, including age, sex, body mass index, creatinine level, glomerular filtration rate of allograft, side of graft kidney, number of renal arteries, duration of surgical procedure, and warm ischemic time, were compared between the midline and low transverse incision groups. When we compared the midline versus low transverse incision groups, duration of surgical procedure (P = .043), postoperative day 3 glomerular filtration rate (P = .017), and postoperative day 3 pain score (P = .049) were significantly higher in the low transverse incision group versus the midline incision group. Postoperative day 3 results for duration of hospitalization (P = .030) and pain score (P = .021) were also significantly higher in the low transverse versus midline incision groups when we focused on patients with left nephrectomy. Hand-assisted laparoscopic donor nephrectomy with low transverse incision is more painful and necessitates a longer hospital stay and longer surgical procedure. Despite these disadvantages, hand-assisted laparoscopic donor nephrectomy with low transverse incision can offer a better cosmetic outcome with no definitive differences regarding renal function compared with a midline incision. Surgeons should consider these aspects when deciding on the best method for donor nephrectomy.

The effects of α-lipoic acid on aortic injury and hypertension in the rat remnant kidney (5/6 nephrectomy) model.

PubMed

Ergür, Bekir Uğur; Çilaker Mıcılı, Serap; Yılmaz, Osman; Akokay, Pınar

2015-06-01

The present study was designed to investigate the effects of α-lipoic acid on the abdominal aorta and hypertension in a remnant kidney model histomorphometrically, immunohistochemically, and ultrastructurally. We surgically reduced the renal tissue mass to 5/6 by applying a remnant kidney model. The rats were divided into 4 groups: Group 1- control group, Group 2- lipoic acid group, Group 3- 5/6 nephrectomy group, and Group IV: 5/6 nephrectomy+lipoic acid-treated group. Lipoic acid solution 100 mg/kg was administered by oral gavage for 8 weeks to Groups II and IV. At the end of the experiment, systemic mean blood pressure was monitored. Then, aortic tissues were removed and fixed. After routine histological procedures, tissue sections were examined histochemically, immunohistochemically (type I angiotensin receptor, vascular endothelial growth factor, alpha-smooth muscle actin), and ultrastructurally. The blood pressure measurements in 5/6 nephrectomy group were significantly higher compared to other groups. In the 5/6 nephrectomy+lipoic acid group, measured blood pressure values and tunica media thickness were significantly lower than in the 5/6 nephrectomy group. In the 5/6 nephrectomy+lipoic acid group, decreased aortic wall thickness, regularity in the structure of elastic fibrils, and more organized elastic lamellae were seen. The expression of type I angiotensin receptor, vascular endothelial growth factor, alpha-smooth muscle actin in the 5/6 nephrectomy+lipoic acid group was decreased compared to the 5/6 nephrectomy group. In the present study, we found that α-lipoic acid could be a favorable agent for the target organ effects of secondary hypertension.

Robotic unclamped "minimal-margin" partial nephrectomy: ongoing refinement of the anatomic zero-ischemia concept.

PubMed

Satkunasivam, Raj; Tsai, Sheaumei; Syan, Sumeet; Bernhard, Jean-Christophe; de Castro Abreu, Andre Luis; Chopra, Sameer; Berger, Andre K; Lee, Dennis; Hung, Andrew J; Cai, Jie; Desai, Mihir M; Gill, Inderbir S

2015-10-01

Anatomic partial nephrectomy (PN) techniques aim to decrease or eliminate global renal ischemia. To report the technical feasibility of completely unclamped "minimal-margin" robotic PN. We also illustrate the stepwise evolution of anatomic PN surgery with related outcomes data. This study was a retrospective analysis of 179 contemporary patients undergoing anatomic PN at a tertiary academic institution between October 2009 and February 2013. Consecutive consented patients were grouped into three cohorts: group 1, with superselective clamping and developmental-curve experience (n = 70); group 2, with superselective clamping and mature experience (n = 60); and group 3, which had completely unclamped, minimal-margin PN (n = 49). Patients in groups 1 and 2 underwent superselective tumor-specific devascularization, whereas patients in group 3 underwent completely unclamped minimal-margin PN adjacent to the tumor edge, a technique that takes advantage of the radially oriented intrarenal architecture and anatomy. Primary outcomes assessed the technical feasibility of robotic, completely unclamped, minimal-margin PN; short-term changes in estimated glomerular filtration rate (eGFR); and development of new-onset chronic kidney disease (CKD) stage >3. Secondary outcome measures included perioperative variables, 30-d complications, and histopathologic outcomes. Demographic data were similar among groups. For similarly sized tumors (p = 0.13), percentage of kidney preserved was greater (p = 0.047) and margin width was narrower (p = 0.0004) in group 3. In addition, group 3 had less blood loss (200, 225, and 150ml; p = 0.04), lower transfusion rates (21%, 23%, and 4%; p = 0.008), and shorter hospital stay (p = 0.006), whereas operative time and 30-d complication rates were similar. At 1-mo postoperatively, median percentage reduction in eGFR was similar (7.6%, 0%, and 3.0%; p = 0.53); however, new-onset CKD stage >3 occurred less frequently in group 3 (23%, 10%, and 2%; p = 0.003). Study limitations included retrospective analysis, small sample size, and short follow-up. We developed an anatomically based technique of robotic, unclamped, minimal-margin PN. This evolution from selective clamped to unclamped PN may further optimize functional outcomes but requires external validation and longer follow-up. The technical evolution of partial nephrectomy surgery is aimed at eliminating global renal damage from the cessation of blood flow. An unclamped minimal-margin technique is described and may offer renal functional advantage but requires long-term follow-up and validation at other institutions. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

PubMed Central

2012-01-01

Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery) may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH) are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10), and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC)-controlled Phase I/II study (N = 7) in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10): All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min) of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7): Hemostatic success at 10 min (primary endpoint) was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial hemorrhage as a replacement for sutures. The study was suspended after 7/30 planned subjects were enrolled. Conclusions The first-in-man trial of fibrin pad demonstrated its safety and efficacy as an adjunctive hemostatic technique for mild-to-moderate bleeding in partial nephrectomy. The study also suggested that the product should not replace sutures or meticulous surgical techniques for the treatment of severe arterial hemorrhage. Trial registration Phase I/II trial, NCT00598130 PMID:23137020

Cost effective laparoendoscopic single-site surgery with a reusable platform.

PubMed

Schwentner, C; Todenhöfer, T; Seibold, J; Alloussi, S; Aufderklamm, S; Mischinger, J; Stenzl, A; Gakis, G

2013-01-01

Many disposable platforms have been applied in laparoendoscopic single-site surgery (LESS). Besides technical issues, cost is one of the limiting factors for its widespread acceptance. The current study describes the first completely reusable LESS-platform. We performed LESS-procedures in 52 patients including nephrectomy (18), adrenalectomy (2), partial nephrectomy (3), pyeloplasty (4), renal cyst ablation (4), pelvic lymphadenectomy (15), and lymphocele ablation (6). All procedures were conducted using a novel reusable single-port device (X-Cone, Karl-Storz) with a simplified set of instruments. We obtained perioperative and demographic data, including a visual analogue pain scale (VAS), and a complication reporting system based on Clavien grading. Mean age was 50.04 y. Conversion to standard laparoscopy was necessary in 3 cases and addition of a needlescopic instrument in 6 cases. There was no open conversion. Intra- and postoperative complications occurred in 3 (Clavien II in 2 and III in 1) cases. Mean operative time was 110, 90, and 89 min, and hospital stay was 4.9, 3.1, and 3.6 d for nephrectomy, pelvic lymphadenectomy, and pyeloplasty, respectively. Mean VAS was 2.13, 1.07, and 1.5 while blood loss was 81.3 mL, 25.67 mL, and 17.5 mL, respectively. Mean lymph node yield was 15 (range, 8 to 21). A completely reusable LESS-platform is applicable to various uses in urology, yielding favorable functional and cosmetic results. Reusable materials are useful to reduce the cost of LESS, further increasing its acceptance. LESS with a completely reusable platform is more cost effective than standard laparoscopy.

Prospective clinical trial of preoperative sunitinib in patients with renal cell carcinoma.

PubMed

Hellenthal, Nicholas J; Underwood, Willie; Penetrante, Remedios; Litwin, Alan; Zhang, Shaozeng; Wilding, Gregory E; Teh, Bin T; Kim, Hyung L

2010-09-01

Sunitinib is an approved treatment for metastatic renal cell carcinoma. We performed a prospective clinical trial to evaluate the safety and clinical response to sunitinib administered before nephrectomy in patients with localized or metastatic clear cell renal cell carcinoma. Patients with biopsy proven clear cell renal cell carcinoma were enrolled in the study and treated with 37.5 mg sunitinib malate daily for 3 months before nephrectomy. The primary end point was safety. In an 18-month period 20 patients were enrolled. The most common toxicities were gastrointestinal symptoms and hematological effects. Grade 3 toxicity developed in 6 patients (30%). No surgical complications were attributable to sunitinib treatment. Of the 20 patients 17 (85%) experienced reduced tumor diameter (mean change -11.8%, range -27% to 11%) and cross-sectional area (mean change -27.9%, range -43% to 23%). Enhancement on contrast enhanced computerized tomography decreased in 15 patients (mean HU change -22%, range -74% to 29%). After tumor reduction 8 patients with cT1b disease underwent laparoscopic partial nephrectomy. Surgical parameters, such as blood loss, transfusion rate, operative time and complications, were similar to those in patients who underwent surgery during the study period and were not enrolled in the trial. Preoperative treatment with sunitinib is safe. Sunitinib decreased the size of primary renal cell carcinoma in 17 of 20 patients. Future trials can be considered to evaluate neoadjuvant sunitinib to maximize nephron sparing and decrease the recurrence of high risk, localized renal cell carcinoma. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prospective clinical trial of preoperative sunitinib in patients with renal cell carcinoma.

PubMed Central

Hellenthal, Nicholas J.; Underwood, Willie; Penetrante, Remedios; Litwin, Alan; Zhang, Shaozeng; Wilding, Gregory E.; Teh, Bin T.; Kim, Hyung L.

2011-01-01

Introduction Sunitinib is an approved treatment for metastatic renal cell carcinoma (RCC). A prospective clinical trial was conducted to evaluate the safety and clinical response to sunitinib administered prior to nephrectomy in patients with localized or metastatic clear cell RCC. Methods Patients with biopsy-proven clear cell RCC were enrolled and treated with sunitinib malate, 37.5 mg daily, for 3 months prior to nephrectomy. The primary endpoints was safety. Results Twenty patients were enrolled during an 18 month period. The most common toxicities were GI symptoms and hematologic. Grade 3 toxicities occurred in 6 patients (30%). No surgical complications were attributable to treatment with sunitinib. Seventeen of the 20 patients (85%) experienced a decrease in tumor diameter (mean change −11.8%, range −27% to 11%) and cross-sectional area (mean change −27.9%, range −43% to 23%). Enhancement on contrast-enhanced CT decreased in 15 patients, with a mean change in Hounsfield units of −22% (range −74% to 29%). Following a decrease in tumor size, 8 patients with cT1b tumors underwent laparoscopic partial nephrectomy. Surgical parameters such as blood loss, transfusion rate, operative time, and complications were similar to those who underwent surgery during the study period and were not enrolled on the trial. Conclusions Preoperative treatment with sunitinib is safe. Sunitinib decreased the size of primary RCC in 17 of 20 patients, and future trials can be considered to evaluate the use of neoadjuvant sunitinib to maximize nephron-sparing and decrease recurrence risk for high-risk, localized RCC. PMID:20643461

Nutritive evaluation of a non-conventional leafy vegetable (Pereskia aculeata Miller).

PubMed

Takeiti, Cristina Y; Antonio, Graziella C; Motta, Eliana M P; Collares-Queiroz, Fernanda P; Park, Kil J

2009-01-01

Pereskia aculeata Miller is a native cactus that can be found in Brazil and is called 'ora-pro-nobis' (OPN). Many people from poor communities consume the dark green leaves of OPN as a vegetable. The objective of the present work was to evaluate the nutritional components in terms of proximate composition, minerals, vitamins, protein content and their in vitro protein digestibility. OPN leaves showed remarkable levels of total dietary fiber (39.1% dry basis), minerals (calcium, magnesium, manganese and zinc) and vitamins (vitamin A, vitamin C and folic acid). Among amino acids, tryptophan was the most abundant (20.5% of the total amino acids) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed small peptides, inferior to 6.5 kDa, and four major bands (61 kDa, 53 kDa, 33 kDa, and 15 kDa). The protein digestibility corrected amino acid score showed the lowest value of sulfur-amino acids (Met+Cys). OPN leaves could be considered a good source of minerals, vitamins and amino acids, and may serve as a potential functional ingredient.

Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain

NASA Technical Reports Server (NTRS)

Owan, I.; Burr, D. B.; Turner, C. H.; Qiu, J.; Tu, Y.; Onyia, J. E.; Duncan, R. L.

1997-01-01

Mechanical force applied to bone produces two localized mechanical signals on the cell: deformation of the extracellular matrix (substrate strain) and extracellular fluid flow. To study the effects of these stimuli on osteoblasts, MC3T3-E1 cells were grown on type I collagen-coated plastic plates and subjected to four-point bending. This technique produces uniform levels of physiological strain and fluid forces on the cells. Each of these parameters can be varied independently. Osteopontin (OPN) mRNA expression was used to assess the anabolic response of MC3T3-E1 cells. When fluid forces were low, neither strain magnitude nor strain rate was correlated with OPN expression. However, higher-magnitude fluid forces significantly increased OPN message levels independently of the strain magnitude or rate. These data indicate that fluid forces, and not mechanical stretch, influence OPN expression in osteoblasts and suggest that fluid forces induced by extracellular fluid flow within the bone matrix may play an important role in bone formation in response to mechanical loading.

Osteopontin deficiency ameliorates Alport pathology by preventing tubular metabolic deficits

PubMed Central

Ding, Wen; Goncalves, Stefania; Goldstein, Bradley J.; Sabater, Alfonso L.; Kloosterboer, Amy; Ritter, Portia; Lambert, Guerline; Mendez, Armando J.

2018-01-01

Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. In Alport renal tubules we found extensive cholesterol accumulation and increased protein expression of dynamin-3 (DNM3) and LDL receptor (LDLR) in addition to dysmorphic mitochondria with defective bioenergetics. Increased pathological cholesterol influx was confirmed by a remarkably increased uptake of injected DiI-LDL cholesterol by Alport renal tubules, and by the improved lifespan of the Alport mice when crossed with the Ldlr–/– mice with defective cholesterol influx. Moreover, OPN-deficient Alport mice demonstrated significant reduction of DNM3 and LDLR expression. In human renal epithelial cells, overexpressing DNM3 resulted in elevated LDLR protein expression and defective mitochondrial respiration. Our results suggest a potentially new pathway in Alport pathology where tubular OPN causes DNM3- and LDLR-mediated enhanced cholesterol influx and impaired mitochondrial respiration. PMID:29563333

Osteopontin deficiency ameliorates Alport pathology by preventing tubular metabolic deficits.

PubMed

Ding, Wen; Yousefi, Keyvan; Goncalves, Stefania; Goldstein, Bradley J; Sabater, Alfonso L; Kloosterboer, Amy; Ritter, Portia; Lambert, Guerline; Mendez, Armando J; Shehadeh, Lina A

2018-03-22

Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. In Alport renal tubules we found extensive cholesterol accumulation and increased protein expression of dynamin-3 (DNM3) and LDL receptor (LDLR) in addition to dysmorphic mitochondria with defective bioenergetics. Increased pathological cholesterol influx was confirmed by a remarkably increased uptake of injected DiI-LDL cholesterol by Alport renal tubules, and by the improved lifespan of the Alport mice when crossed with the Ldlr-/- mice with defective cholesterol influx. Moreover, OPN-deficient Alport mice demonstrated significant reduction of DNM3 and LDLR expression. In human renal epithelial cells, overexpressing DNM3 resulted in elevated LDLR protein expression and defective mitochondrial respiration. Our results suggest a potentially new pathway in Alport pathology where tubular OPN causes DNM3- and LDLR-mediated enhanced cholesterol influx and impaired mitochondrial respiration.

Light-induced rapid Ca2+ response and MAPK phosphorylation in the cells heterologously expressing human OPN5

PubMed Central

Sugiyama, Takashi; Suzuki, Hirobumi; Takahashi, Takeo

2014-01-01

Molecular imaging is a powerful tool for investigating intracellular signalling, but it is difficult to acquire conventional fluorescence imaging from photoreceptive cells. Here we demonstrated that human opsin5 (OPN5) photoreceptor mediates light-induced Ca2+ response in human embryonic kidney (HEK293) and mouse neuroblastoma (Neuro2a) cell lines using a luminescence imaging system with a fluorescent indicator and a newly synthesized bioluminescent indicator. Weak light fluorescence and bioluminescence imaging revealed rapid and transient light-stimulated Ca2+ release from thapsigargin-sensitive Ca2+ stores, whereas long-lasting Ca2+ elevation was observed using a conventional fluorescence imaging system. Bioluminescence imaging also demonstrated that OPN5 activation in HEK293 cells induced a decrease in pertussis toxin–sensitive cAMP, confirming previous reports. In addition, ultraviolet radiation induced the phosphorylation of mitogen-activated protein kinases when OPN5 was stimulated in Neuro2a cells. These findings suggest that the combination of these imaging approaches may provide a new means to investigate the physiological characteristics of photoreceptors. PMID:24941910

Biochemical markers of bone turnover in diagnosis of myeloma bone disease.

PubMed

Dizdar, Omer; Barista, Ibrahim; Kalyoncu, Umut; Karadag, Omer; Hascelik, Gulsen; Cila, Aysenur; Pinar, Asli; Celik, Ismail; Kars, Ayse; Tekuzman, Gulten

2007-03-01

This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1alpha (MIP-1alpha), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1alpha, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Twenty-two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP-1alpha, and urine DPD were significantly higher in MM patients with bone disease than in controls (P<0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls (P<0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls (P<0.001). The serum OPN and MIP-1alpha levels of the patients were significantly correlated with beta2-microglobulin and lactate dehydrogenase levels (P<0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1alpha needs to be further investigated. Copyright (c) 2006 Wiley-Liss, Inc.

Melanopsin mediates light-dependent relaxation in blood vessels

PubMed Central

Sikka, Gautam; Hussmann, G. Patrick; Pandey, Deepesh; Cao, Suyi; Hori, Daijiro; Park, Jong Taek; Steppan, Jochen; Kim, Jae Hyung; Barodka, Viachaslau; Myers, Allen C.; Santhanam, Lakshmi; Nyhan, Daniel; Halushka, Marc K.; Koehler, Raymond C.; Snyder, Solomon H.; Shimoda, Larissa A.; Berkowitz, Dan E.

2014-01-01

Melanopsin (opsin4; Opn4), a non-image-forming opsin, has been linked to a number of behavioral responses to light, including circadian photo-entrainment, light suppression of activity in nocturnal animals, and alertness in diurnal animals. We report a physiological role for Opn4 in regulating blood vessel function, particularly in the context of photorelaxation. Using PCR, we demonstrate that Opn4 (a classic G protein-coupled receptor) is expressed in blood vessels. Force-tension myography demonstrates that vessels from Opn4−/− mice fail to display photorelaxation, which is also inhibited by an Opn4-specific small-molecule inhibitor. The vasorelaxation is wavelength-specific, with a maximal response at ∼430–460 nm. Photorelaxation does not involve endothelial-, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling but is associated with vascular hyperpolarization, as shown by intracellular membrane potential measurements. Signaling is both soluble guanylyl cyclase- and phosphodiesterase 6-dependent but protein kinase G-independent. β-Adrenergic receptor kinase 1 (βARK 1 or GRK2) mediates desensitization of photorelaxation, which is greatly reduced by GRK2 inhibitors. Blue light (455 nM) regulates tail artery vasoreactivity ex vivo and tail blood blood flow in vivo, supporting a potential physiological role for this signaling system. This endogenous opsin-mediated, light-activated molecular switch for vasorelaxation might be harnessed for therapy in diseases in which altered vasoreactivity is a significant pathophysiologic contributor. PMID:25404319

Endogenous osteopontin induces myocardial CCL5 and MMP-2 activation that contributes to inflammation and cardiac remodeling in a mouse model of chronic Chagas heart disease.

PubMed

Caballero, Eugenia Pérez; Santamaría, Miguel H; Corral, Ricardo S

2018-01-01

Cardiac dysfunction with progressive inflammation and fibrosis is a hallmark of Chagas disease caused by persistent Trypanosoma cruzi infection. Osteopontin (OPN) is a pro-inflammatory cytokine that orchestrates mechanisms controlling cell recruitment and cardiac architecture. Our main goal was to study the role of endogenous OPN as a modulator of myocardial CCL5 chemokine and MMP-2 metalloproteinase, and its pathological impact in a murine model of Chagas heart disease. Wild-type (WT) and OPN-deficient (spp1 -/-) mice were parasite-infected (Brazil strain) for 100days. Both groups developed chronic myocarditis with similar parasite burden and survival rates. However, spp1 -/- infection showed lower heart-to-body ratio (P<0.01) as well as reduced inflammatory pathology (P<0.05), CCL5 expression (P<0.05), myocyte size (P<0.05) and fibrosis (P<0.01) in cardiac tissues. Intense OPN labeling was observed in inflammatory cells recruited to infected heart (P<0.05). Plasma concentration of MMP-2 was higher (P<0.05) in infected WT than in spp1 -/- mice. Coincidently, specific immunostaining revealed increased gelatinase expression (P<0.01) and activity (P<0.05) in the inflamed hearts from T. cruzi WT mice, but not in their spp1 -/- littermates. CCL5 and MMP-2 induction occurred preferentially (P<0.01) in WT heart-invading CD8 + T cells and was mediated via phospho-JNK MAPK signaling. Heart levels of OPN, CCL5 and MMP-2 correlated (P<0.01) with collagen accumulation in the infected WT group only. Endogenous OPN emerges as a key player in the pathogenesis of chronic Chagas heart disease, through the upregulation of myocardial CCL5/MMP-2 expression and activities resulting in pro-inflammatory and pro-hypertrophic events, cardiac remodeling and interstitial fibrosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Renoduodenal Fistula After Transcatheter Embolization of Renal Angiomyolipoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheth, Rahul A.; Feldman, Adam S.; Walker, T. Gregory, E-mail: tgwalker@partners.org

Transcatheter embolization of renal angiomyolipomas is a routinely performed, nephron-sparing procedure with a favorable safety profile. Complications from this procedure are typically minor in severity, with postembolization syndrome the most common minor complication. Abscess formation is a recognized but uncommon major complication of this procedure and is presumably due to superinfection of the infarcted tissue after arterial embolization. In this case report, we describe the formation of a renoduodenal fistula after embolization of an angiomyolipoma, complicated by intracranial abscess formation and requiring multiple percutaneous drainage procedures and eventual partial nephrectomy.

[Cortico-suprarenal carcinoma].

PubMed

Alecu, L; Costan, I; Viţalariu, Adriana; Lungu, C; Obrocea, F; Gulinescu, L

2002-01-01

The authors show the case of a 69 years old male with a large corticosuprarenalian tumor that was detected on an random abdominal echographic examination. The patient was operated in the General Surgery Department. of Prof. Agrippa Ionescu Hospital, Bucharest. We performed ablation of the large left suprarenalian gland malign tumor with left nephrectomy, splenectomy and partial pancreatectomy. The hystopathological examination reveals a diffuse corticosuprenalian carcinoma. The case is interesting because of low incidence of this kind of malign tumor and also of the unusual tumor evolution in a long time up to its large size (12 cm in diameter).

Human osteopontin splicing isoforms: known roles, potential clinical applications and activated signaling pathways.

PubMed

Gimba, E R; Tilli, T M

2013-04-30

Human osteopontin is subject to alternative splicing, which generates three isoforms, termed OPNa, OPNb and OPNc. These variants show specific expression and roles in different cell contexts. We present an overview of current knowledge of the expression profile of human OPN splicing isoforms (OPN-SIs), their tissue-specific roles, and the pathways mediating their functional properties in different pathophysiological conditions. We also describe their putative application as biomarkers, and their potential use as therapeutic targets by using antibodies, oligonucleotides or siRNA molecules. This synthesis provides new clues for a better understanding of human OPN splice variants, their roles in normal and pathological conditions, and their possible clinical applications. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Radical Nephrectomy for Primary Retroperitoneal Liposarcoma Near the Kidney has a Beneficial Effect on Disease-Free Survival.

PubMed

Rhu, Jinsoo; Cho, Chan Woo; Lee, Kyo Won; Park, Hyojun; Park, Jae Berm; Choi, Yoon-La; Kim, Sung Joo

2018-01-01

The purpose of this study is to analyze the clinical impact of radical nephrectomy on retroperitoneal liposarcoma near the kidney. Data of patients who underwent surgery for unilateral primary retroperitoneal liposarcoma near the kidney were retrospectively collected. Patients were divided into four groups according to whether they underwent nephrectomy and combined resection of other organs. Kaplan-Meier survival analysis was used to estimate disease-free survival and overall survival. Multivariable Cox analysis was used to analyze factors related to disease-free survival and overall survival. Nephrectomy (HR = 0.260, CI = 0.078-0.873, p = 0.029) had a beneficial effect on disease-free survival, while interaction model of nephrectomy*other organ resection (HR = 4.655, CI = 1.767-12.263, p = 0.002) showed poor disease-free survival. Other organ resection was not related to disease-free survival (HR = 1.543, CI = 0.146-16.251, p = 0.718). Operation method (p = 0.007) and FNCLCC grade (p < 0.001; G2, HR = 1.833, CI = 0.684-4.915, p = 0.228; G3, HR = 9.190, CI = 3.351-25.199, p < 0.001) were significant factors for disease-free survival. While combined organ resection without nephrectomy group (HR = 1.604, CI = 0.167-15.370, p = 0.682) and radical nephrectomy with combined organ resection group (HR = 1.309, CI = 0.448-3.825, p = 0.622) did not show significant difference in disease-free survival from the mass excision only group, radical nephrectomy without combined organ resection group (HR = 0.279, CI = 0.078-0.991, p = 0.048) showed superior disease-free survival. Radical nephrectomy of unilateral primary retroperitoneal liposarcoma near the kidney has a beneficial effect on disease-free survival.

[Which surgical technique should we perform for benign renal disease in children?].

PubMed

Saura, L; Aparicio, L García; Julià, V; Ribó, J M; Rovira, J; Rodó, J; Tarrado, X; Prat, J; Cáceres, F; Morales, L

2007-01-01

The aim of this paper is to analyze our experience in different surgical techniques to perform a nephrectomy for benign renal diseases in children. From 1993 to 2005 we have performed 98 nephrectomies. We have three groups of patients depending on the surgical technique: open nephrectomy (ON), transperitoneal laparoscopic nephrectomy (TLN) and retroperitoneal laparoscopic nephrectomy (RLN). ON was performed in 36 patients. Mean age was 3.3 years. TLN was performed in 39 patients. Mean age was 4.7 years old. RLN was performed in 23 patients. Mean age was 3.6 years old. Criteria to nephrectomy was a renographic function under 19%. We have compared the three surgical techniques in relation with surgical time and mean hospital stay. Mean operative time was 126.2 minutes in ON, 132.3 minutes in TLN and 134.1 minutes in RLN. Mean stay was 5.02 days in ON, 2.35 days in TLN and 1.86 days in RLN. The median hospital stay of the ON group is significantly longer than that of NLT and NR groups (p < 0.05). However, there are no differences related to surgical time between all the groups. Nephrectomy may be performed for benign disease in children using less invasive surgical techniques. They are associated with minimal morbidity, minimal postoperative discomfort, improve cosmesis and a shorter hospital stay. However, we haven't found differences between TLN and RLN.

Acute Ketamine Administration Corrects Abnormal Inflammatory Bone Markers in Major Depressive Disorder

PubMed Central

Kadriu, Bashkim; Gold, Philip W; Luckenbaugh, David A; Lener, Marc S; Ballard, Elizabeth D; Niciu, Mark J; Henter, Ioline D; Park, Lawrence T; De Sousa, Rafael Teixeira; Yuan, Peixiong; Machado-Vieira, Rodrigo; Zarate, Carlos A

2017-01-01

Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation—the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)—play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 minutes, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness. PMID:28555075

Na+/H+ exchanger isoform 1-induced osteopontin expression facilitates cardiac hypertrophy through p90 ribosomal S6 kinase.

PubMed

Abdulrahman, Nabeel; Jaspard-Vinassa, Beatrice; Fliegel, Larry; Jabeen, Aayesha; Riaz, Sadaf; Gadeau, Alain-Pierre; Mraiche, Fatima

2018-05-01

Cardiovascular diseases are the leading cause of death worldwide. One in three cases of heart failure is due to dilated cardiomyopathy. The Na + /H + exchanger isoform 1 (NHE1), a multifunctional protein and the key pH regulator in the heart, has been demonstrated to be increased in this condition. We have previously demonstrated that elevated NHE1 activity induced cardiac hypertrophy in vivo. Furthermore, the overexpression of active NHE1 elicited modulation of gene expression in cardiomyocytes including an upregulation of myocardial osteopontin (OPN) expression. To determine the role of OPN in inducing NHE1-mediated cardiomyocyte hypertrophy, double transgenic mice expressing active NHE1 and OPN knockout were generated and assessed by echocardiography and the cardiac phenotype. Our studies showed that hearts expressing active NHE1 exhibited cardiac remodeling indicated by increased systolic and diastolic left ventricular internal diameter and increased ventricular volume. Moreover, these hearts demonstrated impaired function with decreased fractional shortening and ejection fraction. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA was upregulated, and there was an increase in heart cell cross-sectional area confirming the cardiac hypertrophic effect. Moreover, NHE1 transgenic mice also showed increased collagen deposition, upregulation of CD44 and phosphorylation of p90 ribosomal s6 kinase (RSK), effects that were regressed in OPN knockout mice. In conclusion, we developed an interesting comparative model of active NHE1 transgenic mouse lines which express a dilated hypertrophic phenotype expressing CD44 and phosphorylated RSK, effects which were regressed in absence of OPN.

Functional preservation and variation in the cone opsin genes of nocturnal tarsiers

PubMed Central

Ong, Perry S.; Perry, George H.

2017-01-01

The short-wavelength sensitive (S-) opsin gene OPN1SW is pseudogenized in some nocturnal primates and retained in others, enabling dichromatic colour vision. Debate on the functional significance of this variation has focused on dark conditions, yet many nocturnal species initiate activity under dim (mesopic) light levels that can support colour vision. Tarsiers are nocturnal, twilight-active primates and exemplary visual predators; they also express different colour vision phenotypes, raising the possibility of discrete adaptations to mesopic conditions. To explore this premise, we conducted a field study in two stages. First, to estimate the level of functional constraint on colour vision, we sequenced OPN1SW in 12 wild-caught Philippine tarsiers (Tarsius syrichta). Second, to explore whether the dichromatic visual systems of Philippine and Bornean (Tarsius bancanus) tarsiers—which express alternate versions of the medium/long-wavelength sensitive (M/L-) opsin gene OPN1MW/OPN1LW—confer differential advantages specific to their respective habitats, we used twilight and moonlight conditions to model the visual contrasts of invertebrate prey. We detected a signature of purifying selection for OPN1SW, indicating that colour vision confers an adaptive advantage to tarsiers. However, this advantage extends to a relatively small proportion of prey–background contrasts, and mostly brown arthropod prey amid leaf litter. We also found that the colour vision of T. bancanus is advantageous for discriminating prey under twilight that is enriched in shorter (bluer) wavelengths, a plausible idiosyncrasy of understorey habitats in Borneo. This article is part of the themed issue ‘Vision in dim light’. PMID:28193820

Two Opsin 3-Related Proteins in the Chicken Retina and Brain: A TMT-Type Opsin 3 Is a Blue-Light Sensor in Retinal Horizontal Cells, Hypothalamus, and Cerebellum.

PubMed

Kato, Mutsuko; Sugiyama, Takashi; Sakai, Kazumi; Yamashita, Takahiro; Fujita, Hirofumi; Sato, Keita; Tomonari, Sayuri; Shichida, Yoshinori; Ohuchi, Hideyo

2016-01-01

Opsin family genes encode G protein-coupled seven-transmembrane proteins that bind a retinaldehyde chromophore in photoreception. Here, we sought potential as yet undescribed avian retinal photoreceptors, focusing on Opsin 3 homologs in the chicken. We found two Opsin 3-related genes in the chicken genome: one corresponding to encephalopsin/panopsin (Opn3) in mammals, and the other belonging to the teleost multiple tissue opsin (TMT) 2 group. Bioluminescence imaging and G protein activation assays demonstrated that the chicken TMT opsin (cTMT) functions as a blue light sensor when forced-expressed in mammalian cultured cells. We did not detect evidence of light sensitivity for the chicken Opn3 (cOpn3). In situ hybridization demonstrated expression of cTMT in subsets of differentiating cells in the inner retina and, as development progressed, predominant localization to retinal horizontal cells (HCs). Immunohistochemistry (IHC) revealed cTMT in HCs as well as in small numbers of cells in the ganglion and inner nuclear layers of the post-hatch chicken retina. In contrast, cOpn3-IR cells were found in distinct subsets of cells in the inner nuclear layer. cTMT-IR cells were also found in subsets of cells in the hypothalamus. Finally, we found differential distribution of cOpn3 and cTMT proteins in specific cells of the cerebellum. The present results suggest that a novel TMT-type opsin 3 may function as a photoreceptor in the chicken retina and brain.

Prostate Cancer Progression and Serum SIBLING (Small Integrin Binding N-Linked Glycoprotein)Levels

DTIC Science & Technology

2007-10-01

termed SIBLINGs (for small integrin binding ligand N-linked glycoproteins) whose members include bone sialoprotein (BSP), osteopontin (OPN), dentin...enzyme-linked immunosorbent assays (ELISAs) for quantitatively determining the levels of bone sialoprotein (BSP), osteopontin (OPN), dentin...synthesized as a chimeric protein, composed of three parts: dentin sialoprotein (DSP), dentin glycoprotein (DGP) and dentin phosphoprotein (DPP, also

Immunocytochemical characterization of ectopic enamel deposits and cementicles in human teeth.

PubMed

Bosshardt, Dieter D; Nanci, Antonio

2003-02-01

Despite the relative frequency and clinical relevance of radicular enamel deposits and cementicles, their etiology and nature are unknown. The purpose of the present study was therefore to evaluate the presence and distribution of mineralization-associated non-collagenous matrix proteins (NCPs) in various types of root-associated ectopic mineralizations. Human teeth were processed for embedding in epoxy or acrylic resins. Tissue sections were incubated with antibodies to amelogenins (AMEL), bone sialoprotein (BSP), and osteopontin (OPN). Radicular enamel deposits contained residual organic matrix that labeled for AMEL. In contrast, BSP and OPN were not detected in the residual enamel matrix, they were found in the cementum deposited on its surface as well as in collagen-free cementicle-like structures in the adjacent periodontal ligament. True cementicles consisted of a collagenous matrix intermixed with a non-collagenous ground substance. Labeling for BSP and OPN was mainly associated with the interfibrillar ground substance. No immunoreactivity for AMEL was detected in cementicles. These data indicate that ectopic enamel deposits on the root retain a high amount of AMEL, whereas cementicles contain BSP and OPN, two NCPs typically found in bone and cementum. These NCPs may, like in their normal tissue counterparts, play a role in the mineralization process.

Dilatational band formation in bone

PubMed Central

Poundarik, Atharva A.; Diab, Tamim; Sroga, Grazyna E.; Ural, Ani; Boskey, Adele L.; Gundberg, Caren M.; Vashishth, Deepak

2012-01-01

Toughening in hierarchically structured materials like bone arises from the arrangement of constituent material elements and their interactions. Unlike microcracking, which entails micrometer-level separation, there is no known evidence of fracture at the level of bone’s nanostructure. Here, we show that the initiation of fracture occurs in bone at the nanometer scale by dilatational bands. Through fatigue and indentation tests and laser confocal, scanning electron, and atomic force microscopies on human and bovine bone specimens, we established that dilatational bands of the order of 100 nm form as ellipsoidal voids in between fused mineral aggregates and two adjacent proteins, osteocalcin (OC) and osteopontin (OPN). Laser microdissection and ELISA of bone microdamage support our claim that OC and OPN colocalize with dilatational bands. Fracture tests on bones from OC and/or OPN knockout mice (OC−/−, OPN−/−, OC-OPN−/−;−/−) confirm that these two proteins regulate dilatational band formation and bone matrix toughness. On the basis of these observations, we propose molecular deformation and fracture mechanics models, illustrating the role of OC and OPN in dilatational band formation, and predict that the nanometer scale of tissue organization, associated with dilatational bands, affects fracture at higher scales and determines fracture toughness of bone. PMID:23129653

Surgical navigation in urology: European perspective.

PubMed

Rassweiler, Jens; Rassweiler, Marie-Claire; Müller, Michael; Kenngott, Hannes; Meinzer, Hans-Peter; Teber, Dogu

2014-01-01

Use of virtual reality to navigate open and endoscopic surgery has significantly evolved during the last decade. Current status of seven most interesting projects inside the European Association of Urology section of uro-technology is summarized with review of literature. Marker-based endoscopic tracking during laparoscopic radical prostatectomy using high-definition technology reduces positive margins. Marker-based endoscopic tracking during laparoscopic partial nephrectomy by mechanical overlay of three-dimensional-segmented virtual anatomy is helpful during planning of trocar placement and dissection of renal hilum. Marker-based, iPAD-assisted puncture of renal collecting system shows more benefit for trainees with reduction of radiation exposure. Three-dimensional laser-assisted puncture of renal collecting system using Uro-Dyna-CT realized in an ex-vivo model enables minimal radiation time. Electromagnetic tracking for puncture of renal collecting system using a sensor at the tip of ureteral catheter worked in an in-vivo model of porcine ureter and kidney. Attitude tracking for ultrasound-guided puncture of renal tumours by accelerometer reduces the puncture error from 4.7 to 1.8 mm. Feasibility of electromagnetic and optical tracking with the da Vinci telemanipulator was shown in vitro as well as using in-vivo model of oesophagectomy. Target registration error was 11.2 mm because of soft-tissue deformation. Intraoperative navigation is helpful during percutaneous puncture collecting system and biopsy of renal tumour using various tracking techniques. Early clinical studies demonstrate advantages of marker-based navigation during laparoscopic radical prostatectomy and partial nephrectomy. Combination of different tracking techniques may further improve this interesting addition to video-assisted surgery.

Diffusion of robotics into clinical practice in the United States: process, patient safety, learning curves, and the public health.

PubMed

Mirheydar, Hossein S; Parsons, J Kellogg

2013-06-01

Robotic technology disseminated into urological practice without robust comparative effectiveness data. To review the diffusion of robotic surgery into urological practice. We performed a comprehensive literature review focusing on diffusion patterns, patient safety, learning curves, and comparative costs for robotic radical prostatectomy, partial nephrectomy, and radical cystectomy. Robotic urologic surgery diffused in patterns typical of novel technology spreading among practicing surgeons. Robust evidence-based data comparing outcomes of robotic to open surgery were sparse. Although initial Level 3 evidence for robotic prostatectomy observed complication outcomes similar to open prostatectomy, subsequent population-based Level 2 evidence noted an increased prevalence of adverse patient safety events and genitourinary complications among robotic patients during the early years of diffusion. Level 2 evidence indicated comparable to improved patient safety outcomes for robotic compared to open partial nephrectomy and cystectomy. Learning curve recommendations for robotic urologic surgery have drawn exclusively on Level 4 evidence and subjective, non-validated metrics. The minimum number of cases required to achieve competency for robotic prostatectomy has increased to unrealistically high levels. Most comparative cost-analyses have demonstrated that robotic surgery is significantly more expensive than open or laparoscopic surgery. Evidence-based data are limited but suggest an increased prevalence of adverse patient safety events for robotic prostatectomy early in the national diffusion period. Learning curves for robotic urologic surgery are subjective and based on non-validated metrics. The urological community should develop rigorous, evidence-based processes by which future technological innovations may diffuse in an organized and safe manner.

The Impact of Surgeon Volume on Perioperative Outcomes and Cost for Patients Receiving Robotic Partial Nephrectomy.

PubMed

Khandwala, Yash S; Jeong, In Gab; Kim, Jae Heon; Han, Deok Hyun; Li, Shufeng; Wang, Ye; Chang, Steven L; Chung, Benjamin I

2017-09-01

Little is known about the impact of surgeon volume on the success of the robot-assisted partial nephrectomy (RAPN). The objective of this study was to compare the perioperative outcomes and cost related to RAPN by annual surgeon volumes. Using the Premier Hospital Database, we retrospectively analyzed 39,773 patients who underwent RAPN between 2003 and 2015 in the United States. Surgeons for each index case were grouped into quintiles for each respective year. Outcomes were 90-day postoperative complications, operating room time (ORT), blood transfusion, length of stay, and direct hospital costs. Logistic regression and generalized linear models were used to identify factors predicting complications and cost. After accounting for patient and hospital demographics, high- and very high-volume surgeons had 40% and 42% decreased odds of having major complications (p = 0.045 and p = 0.027, respectively). Surgeons with higher volumes were associated with fewer odds of prolonged ORT (0.68 for low, 0.72 for intermediate, 0.56 for high, 0.44 for very high volume, all p < 0.05) and length of hospital stay (0.67 for intermediate, 0.51 for high, 0.45 for very high volume, all p < 0.01) compared with very low-volume surgeons. The 90-day hospital cost was also significantly lower for the surgeons with higher volume, but the statistical significance diminished after consideration of hospital clustering. Surgeons with very high RAPN volumes were found to have superior perioperative outcomes. Although cost of care appeared to correlate with surgeon volume, there may be other more influential factors predicting cost.

Laparoscopic partial nephrectomy for hilar tumors: oncologic and renal functional outcomes.

PubMed

George, Arvin K; Herati, Amin S; Rais-Bahrami, Soroush; Waingankar, Nikhil; Kavoussi, Louis R

2014-01-01

To present our experience with laparoscopic partial nephrectomy (LPN) for hilar tumors and evaluate intermediate oncologic and renal functional outcomes. A retrospective review of LPN cases performed in 488 patients was performed. Hilar lesions were defined as renal cortical tumors in direct physical contact with the renal artery, vein, or both, as identified on preoperative imaging and confirmed intraoperatively. The clinicopathologic parameters, perioperative course, complications, and oncologic and 6-month renal functional outcomes were analyzed. A total of 488 patients underwent LPN, of which 43 were hilar. The mean tumor size for hilar and nonhilar tumors was 3.6 cm and 3.1 cm, respectively. The mean operative time was shorter for hilar as compared with nonhilar tumors (129.1 minutes vs 141.8 minutes). Mean estimated blood loss was greater in LPN for hilar tumors (311.65 mL vs 298.4 mL). There were no statistically significant differences noted in any of the perioperative parameters investigated despite a higher nephrometry complexity score in the hilar group. Change in estimated glomerular filtration rate at 6 months showed a decrease of 10.9 mL/min and 8.8 mL/min for hilar and nonhilar tumors, respectively (P = NS). There was 1 recurrence detected in the hilar group, with a median follow-up of 41.6 months. In the hands of an experienced laparoscopist, LPN can safely be performed for hilar tumors, with preservation of perioperative outcomes and durable renal functional and oncologic outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Robotic partial nephrectomy shortens warm ischemia time, reducing suturing time kinetics even for an experienced laparoscopic surgeon: a comparative analysis.

PubMed

Faria, Eliney F; Caputo, Peter A; Wood, Christopher G; Karam, Jose A; Nogueras-González, Graciela M; Matin, Surena F

2014-02-01

Laparoscopic and robotic partial nephrectomy (LPN and RPN) are strongly related to influence of tumor complexity and learning curve. We analyzed a consecutive experience between RPN and LPN to discern if warm ischemia time (WIT) is in fact improved while accounting for these two confounding variables and if so by which particular aspect of WIT. This is a retrospective analysis of consecutive procedures performed by a single surgeon between 2002-2008 (LPN) and 2008-2012 (RPN). Specifically, individual steps, including tumor excision, suturing of intrarenal defect, and parenchyma, were recorded at the time of surgery. Multivariate and univariate analyzes were used to evaluate influence of learning curve, tumor complexity, and time kinetics of individual steps during WIT, to determine their influence in WIT. Additionally, we considered the effect of RPN on the learning curve. A total of 146 LPNs and 137 RPNs were included. Considering renal function, WIT, suturing time, renorrhaphy time were found statistically significant differences in favor of RPN (p < 0.05). In the univariate analysis, surgical procedure, learning curve, clinical tumor size, and RENAL nephrometry score were statistically significant predictors for WIT (p < 0.05). RPN decreased the WIT on average by approximately 7 min compared to LPN even when adjusting for learning curve, tumor complexity, and both together (p < 0.001). We found RPN was associated with a shorter WIT when controlling for influence of the learning curve and tumor complexity. The time required for tumor excision was not shortened but the time required for suturing steps was significantly shortened.

Bilateral Wilms' tumor with anaplasia: lessons from the National Wilms' Tumor Study.

PubMed

Hamilton, Thomas E; Green, Daniel M; Perlman, Elizabeth J; Argani, Pedram; Grundy, Paul; Ritchey, Michael L; Shamberger, Robert C

2006-10-01

The purpose of this study was to evaluate whether initial diagnostic technique influenced the ability to identify anaplastic histology, to determine the time interval to diagnosis of anaplasia, and to delineate the incidence of discordant pathology in bilateral Wilms' tumor. We hypothesized that delay in diagnosis of anaplasia could affect time to appropriate surgery and intensive multimodality therapy. One hundred eight-nine children were enrolled in the fourth National Wilms' Tumor Study with synchronous bilateral tumors, 27 of whom were eventually shown to have anaplastic histology. Initial diagnostic technique, time interval to diagnosis of anaplasia, and the incidence of discordant pathology were determined. Anaplasia was identified in 0 of 7 tumors by core needle biopsy, 3 of 9 tumors by open wedge biopsy, and in 7 of 9 cases by partial or complete nephrectomy. The mean duration of first chemotherapy regimen (DD or EE) was 20, 39, and 36 weeks, respectively, before anaplasia was identified at second surgery. Discordant pathology between bilateral tumors was identified on final tissue diagnosis in 20 patients. Only 4 patients had anaplastic tumors in both kidneys. Core needle biopsy did not identify anaplasia in 7 of 7 children. Open biopsy or partial/complete nephrectomy identified anaplasia at initial diagnostic procedure in 10 of 18 children. Twenty of 24 patients at final tissue diagnosis had discordant pathology between the 2 kidneys. Earlier interval incisional biopsy or resection may identify anaplastic histology and limit the duration of chemotherapy targeted to favorable histology for children with bilateral Wilms' tumor and anaplasia.

Simultaneous bilateral robotic partial nephrectomy: Case report and critical evaluation of the technique.

PubMed

Giberti, Claudio; Gallo, Fabrizio; Schenone, Maurizio; Cortese, Pierluigi

2014-06-16

We report our first simultaneous bilateral robot assisted partial nephrectomy (RAPN) in order to show and critically discuss the feasibility of this procedure. Materials and methods A 69-year-old male patient visited our department due to incidental finding of bilateral mesorenal small masses (2.5 cm on the right and 3.5 cm on the left) suspicious for malignancy. We started from the right side with patient in flank position. Port placement: 12-mm periumbilical camera port, two 8-mm robotic ports in wide ''V''configuration, additional 12 mm assistant port on the midline between the umbilicus and symphysis pubis. A right unclamping RAPN with sliding clip renorrhaphy was performed. The trocars were removed and the robot undocked. Without interrupting the anesthesiological procedures, the patient was reported in supine position and, after 180 degrees rotation of the surgical bed, was newly placed in contralateral flank position. Using both the previous periumbilical and midline ports, two other 8-mm robotic trocars were placed. The robot was then redocked and RAPN was also performed on the left side using the same previously reported technique. Results Total time: 285 min. Estimated blood losses: 150 cc. Postoperative period: uneventful. Pathological examination: bilateral renal cell carcinoma, negative surgical margins. Conclusions Our experience was encouraging and confirmed the feasibility and safety of this procedure. The planning of our technique was time and cost effective with cosmetic benefit for the patient. However, we think that an appropriate selection of the patients and a skill in robotic renal surgery are advisable before approaching this type of surgery.

Visual enhancement of laparoscopic partial nephrectomy with 3-charge coupled device camera: assessing intraoperative tissue perfusion and vascular anatomy by visible hemoglobin spectral response.

PubMed

Crane, Nicole J; Gillern, Suzanne M; Tajkarimi, Kambiz; Levin, Ira W; Pinto, Peter A; Elster, Eric A

2010-10-01

We report the novel use of 3-charge coupled device camera technology to infer tissue oxygenation. The technique can aid surgeons to reliably differentiate vascular structures and noninvasively assess laparoscopic intraoperative changes in renal tissue perfusion during and after warm ischemia. We analyzed select digital video images from 10 laparoscopic partial nephrectomies for their individual 3-charge coupled device response. We enhanced surgical images by subtracting the red charge coupled device response from the blue response and overlaying the calculated image on the original image. Mean intensity values for regions of interest were compared and used to differentiate arterial and venous vasculature, and ischemic and nonischemic renal parenchyma. The 3-charge coupled device enhanced images clearly delineated the vessels in all cases. Arteries were indicated by an intense red color while veins were shown in blue. Differences in mean region of interest intensity values for arteries and veins were statistically significant (p >0.0001). Three-charge coupled device analysis of pre-clamp and post-clamp renal images revealed visible, dramatic color enhancement for ischemic vs nonischemic kidneys. Differences in the mean region of interest intensity values were also significant (p <0.05). We present a simple use of conventional 3-charge coupled device camera technology in a way that may provide urological surgeons with the ability to reliably distinguish vascular structures during hilar dissection, and detect and monitor changes in renal tissue perfusion during and after warm ischemia. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Impact of Preexisting Chronic Kidney Disease on the Severity and Recovery of Acute Kidney Injury.

PubMed

Lim, Sung Yoon; Ko, Yoon Sook; Lee, Hee Young; Yang, Ji Hyun; Kim, Myung Gyu; Jo, Sang Kyung; Cho, Won Yong

2018-04-12

Recent observational studies have shown that in chronic kidney disease (CKD) patients, a significantly smaller percentage of patients with an episode of acute kidney injury (AKI) have full recovery of renal function compared to those without CKD. However, precise mechanisms involved in the incomplete repair after AKI with preexisting CKD have not been completely ascertained. Here, we assessed the impact of preexisting CKD on the severity and recovery of AKI in a mouse model of 5/6 nephrectomy. Male CD-1 mice underwent 5/6 nephrectomy (Nx). Six weeks post surgery, ischemia reperfusion injury (IRI) or a sham operation was performed and functional, histological, and various molecular parameters were compared between them. Serum creatinine level on day 1 after IRI was comparable between control and Nx mice. However, serum creatinine remained significantly higher throughout the recovery phase in Nx mice compared to control mice. mRNA and protein expression of the cell cycle regulatory proteins were persistently elevated in Nx mice and this was associated with significantly increased levels of the G1 cell cycle arrest markers. Treatment with a p53 inhibitor following IRI resulted in not only decreased expression of G1 arrest markers but also decreased fibrosis, suggesting that prolonged epithelial G1 cell cycle arrest might be partially responsible for impaired recovery from superimposed AKI on CKD. Taken together, reduced nephron mass have a negative effect on the repair process that is partially mediated by the disruption of the cell cycle regulation. © 2018 S. Karger AG, Basel.

Intraoperative evaluation of renal blood flow during laparoscopic partial nephrectomy with a novel Doppler system.

PubMed

Mues, Adam C; Okhunov, Zhamshid; Badani, Ketan; Gupta, Mantu; Landman, Jaime

2010-12-01

Hemostasis remains a major challenge associated with laparoscopic renal surgery. We evaluated a cost-effective novel Doppler probe (DP) for assessment of vascular control during laparoscopic partial nephrectomy (LPN). We prospectively collected data during LPN procedures. We documented tumor location and size as well as subjective quality of the hilar dissection. The DP was compared with our standard intraoperative ultrasound system (SUS) for the ability to detect blood flow during hilar dissection and to determine parenchymal ischemia around the tumor after clamping of the renal vessels. Twenty patients underwent LPN by a single surgeon. The mean tumor size was 3.0 cm (range: 1.2-6.3 cm). The times to assess the kidney using the SUS and DP were 68.6 seconds (range: 20-155) and 44.5 seconds (range: 15-180), respectively. Evaluation prior to renal hilar clamping demonstrated the presence of blood flow in all 20 patients (100%) using the SUS and in 17 of 20 (85%) using the DP. Similarly, cessation of blood flow with clamping was documented in 100% of cases with SUS and 85% with DP. Persistent flow was detected by both SUS and DP in two patients requiring further dissection and reclamping. Then, both systems detected the absence of flow before tumor resection. With blood flow interruption confirmation, no patient had significant bleeding at the time of renal parenchymal transection. Intraoperative Doppler ultrasound technologies minimize the risk of significant bleeding during LPN. The DP is a small, simple, effective probe that can be used to assess blood flow interruption to the kidney during laparoscopic renal surgery.

The role of hemostatic agents in preventing complications in laparoscopic partial nephrectomy

PubMed Central

y Gregorio, Sergio Alonso; Rivas, Juan Gómez; Bazán, Alfredo Aguilera; Sebastián, Jesús Díez; Martínez-Piñeiro, Luis

2017-01-01

Introduction Nephron-sparing surgery is currently the treatment of choice for renal cell carcinoma stage T1a. During the past years, several hemostatic agents (HA) have been developed in order to reduce surgical complications. We present the results of our series and the impact of the use of HA in the prevention of surgical complications in laparoscopic partial nephrectomies (LPNs). Material and methods We retrospectively analyzed all LPN performed in our center from 2005 to 2012. A total of 77 patients were included for analysis. Patients were divided into two groups: Group A (no use of HA) and Group B (use of HA). HA used included gelatin matrix thrombin (FloSeal) and oxidized regenerated cellulose (Surgicel). Demographics, perioperative variables, and complications were analyzed with a special interest in postoperative bleeding and urinary leakage. Results Median age was 57.17 years old (±12.1), 72.7% were male, most common comorbidities were hypertension (33.8%) and diabetes mellitus (18.2%). All patients had one solitary tumor, and 87% had a tumor ≤4 cm. Renal cell carcinoma was found in 79.2% of cases, and 78.7% were stage pT1a. and were used in 36 cases (46.8%). No differences were found in demographics, perioperative variables, and complications between groups. No conversions to open surgery or perioperative mortality were reported. Conclusions We conclude that in our series the use of a hemostatic agent did not offer benefit in reducing the complication rate over sutures over a bolster. PMID:29410886

National practice patterns and outcomes of pediatric nephrectomy: comparison between urology and general surgery.

PubMed

Suson, Kristina D; Wolfe-Christensen, Cortney; Elder, Jack S; Lakshmanan, Yegappan

2015-05-01

In adults nephrectomy is under the purview of urologists, but pediatric urologists and pediatric general surgeons perform extirpative renal surgery in children. We compared the contemporary performance and outcome of all-cause nephrectomy at pediatric hospitals as performed by pediatric urologists and pediatric general surgeons. We queried the Pediatric Health Information System to identify patients 0 to 18 years old who were treated with nephrectomy between 2004 and 2013 by pediatric urologists and pediatric general surgeons. Data points included age, gender, severity level, mortality risk, complications and length of stay. Patients were compared by APR DRG codes 442 (kidney and urinary tract procedures for malignancy) and 443 (kidney and urinary tract procedures for nonmalignancy). Pediatric urologists performed more all-cause nephrectomies. While pediatric urologists were more likely to operate on patients with benign renal disease, pediatric general surgeons were more likely to operate on children with malignancy. Patients on whom pediatric general surgeons operated had a higher average severity level and were at greater risk for mortality. After controlling for differences patients without malignancy operated on by pediatric urologists had a shorter length of stay, and fewer medical and surgical complications. There was no difference in length of stay, or medical or surgical complications in patients with malignancy. Overall compared to pediatric general surgeons more nephrectomies are performed by pediatric urologists. Short-term outcomes, including length of stay and complication rates, appear better in this data set in patients without malignancy who undergo nephrectomy by pediatric urologists but there is no difference in outcomes when nephrectomy is performed for malignancy. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effect of nephrectomy on the rate and pattern of the disappearance of exogenous gastrin in dogs

PubMed Central

Clendinnen, B. Guy; Reeder, David D.; Brandt, E. N.; Thompson, James C.

1973-01-01

Studies of gastrin metabolism were performed in four dogs before and after nephrectomy. Synthetic human gastrin I was infused for two hours and serum samples were obtained at various times during and after infusion. Serum concentrations of gastrin were measured by radioimmunoassay. A two-compartment model was employed to calculate half-lives under each of four experimental conditions, low and high infusion rates, used both before and after nephrectomy. The model half-life was greatly prolonged after nephrectomy at both infusion rates (from 2·54 min to 5·15 min at the low rate, and from 2·85 min to 7·88 min at the high rate). The metabolic clearance rate, an expression of the rate of catabolism during infusion, decreased significantly after nephrectomy at both infusion rates. These observations indicate that the kidney is an important organ for the catabolism of exogenous gastrin. PMID:4719213

Hilar location is an independent prognostic factor for recurrence in T1 renal cell carcinoma after nephrectomy.

PubMed

Shim, Myungsun; Song, Cheryn; Park, Sejun; Kim, Aram; Choi, Seung-Kwon; Kim, Choung-Soo; Ahn, Hanjong

2015-01-01

We investigated the prognostic significance of tumor location at the renal hilum near the sinus structure on the recurrence in T1 renal cell carcinoma (RCC). A total of 1,818 T1 RCC patients who underwent radical (RN) or partial nephrectomy (PN) from 1997 to 2011 were retrospectively reviewed. A hilar tumor was defined as a tumor abutting the main renal artery and/or vein or its segmental branches, without invasion. We compared the recurrence-free survival (RFS) rates between hilar and nonhilar T1 RCC and analyzed predictors of RFS after nephrectomy. Patients with hilar tumors showed a poorer 5-year RFS compared with nonhilar tumors both in T1a (89.7 vs. 98.5 %, p < 0.001) and T1b (81.6 vs. 95.1 %, p < 0.001) RCCs. Among patients who underwent RN and PN, hilar tumors were associated with lower 5-year RFS (87.6 vs. 97.2 % for RN, 78.1 vs. 98.2 % for PN, both p < 0.001). In T1a hilar tumor, PN was associated with poorer 5-year RFS than RN (79.5 vs. 93.0 %, p < 0.001). In multivariate analysis, a hilar location remained as an independent predictor of recurrence in both T1a and T1b tumors (both p = 0.001). Hilar tumors show a higher recurrence rate than nonhilar counterparts in T1 RCC. In T1a hilar tumors, PN demonstrated poorer RFS than RN. Potential intrinsic renal anatomical or lymphovascular structural differences as well as differences in cancer characteristics need further investigations.

Utility of the RENAL index -Radius; Exophytic/endophytic; Nearness to sinus; Anterior/posterior; Location relative to polar lines- in the management of renal masses.

PubMed

Konstantinidis, C; Trilla, E; Lorente, D; Morote, J

2016-12-01

The growing incidence of renal masses and the wide range of available treatments require predictive tools that support the decision making process. The RENAL index -Radius; Exophytic/endophytic; Nearness to sinus; Anterior/posterior; Location relative to polar lines- helps standardise the anatomy of a renal mass by differentiating 3 groups of complexity. Since the introduction of the index, there have been a growing number of studies, some of which have been conflicting, that have evaluated the clinical utility of its implementation. To analyse the scientific evidence on the relationship between the RENAL index and the main strategies for managing renal masses. A search was conducted in the Medline database, which found 576 references on the RENAL index. In keeping with the PRISM Declaration, we selected 100 abstracts and ultimately reviewed 96 articles. The RENAL index has a high degree of interobserver correlation and has been validated as a predictive nomogram of histological results. In active surveillance, the index has been related to the tumour growth rate and probability of nephrectomy. In ablative therapy, the index has been associated with therapeutic efficacy, complications and tumour recurrence. In partial nephrectomy, the index has been related to the rate of complications, conversion to radical surgery, ischaemia time, function preservation and tumour recurrence, a finding also observed in radical nephrectomy. The RENAL index is an objective, reproducible and useful system as a predictive tool of highly relevant clinical parameters such as the rate of complications, ischaemia time, renal function and oncological results in the various currently accepted treatments for the management of renal masses. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Commentary on "Detailed analysis of morbidity following nephrectomy for renal cell carcinoma in octogenarians." Berger J, Fardoun T, Brassart E, Capon G, Bigot P, Bernhard JC, Rigaud J, Patard JJ, Descazeaud A, Department of Urology, Dupuytren University Hospital, Limoges, France: J Urol 2012;188(3):736-40 (Epub 2012 Jul 19).

PubMed

Boorjian, Stephen

2013-01-01

We evaluated the morbidity of nephrectomy in patients older than 80 years of age. Between June 2002 and March 2011, 2,530 patients underwent surgery for renal tumor at 5 French academic centers. Of these patients, 180 (7.1%) were 80 years of age or older; 22 (12%) and 158 (88%) patients underwent partial and radical nephrectomy, respectively, and 47 (26.1%) of whom were treated with a laparoscopic approach. Mean patient age was 82.3 years. Median Charlson score was 4. Mean preoperative glomerular filtration rate was 47 ml/min. A total of 136 complications were recorded in 70 patients (38.8% of all patients). Of these patients, 28 (15.5%), 25 (13.9%), and 17 (9.4%) experienced 1, 2, and 3 or more complications, respectively. According to the modified Clavien classification grade I, II, III, IV, and V complications were observed in 7, 81, 19, 23, and 6 patients, respectively. The transfusion rate was 31.1% (56). On logistic regression analysis, the parameters of Eastern Cooperative Oncology Group Performance Status 2 to 4 (P = 0.035) and preoperative glomerular filtration rate less than 30 ml/min (P = 0.03) were independent predictive factors of morbidity. Morbidity and mortality are significant in the octogenarian population. The risk of complications should be considered in decision making for patients with renal cell carcinoma who were older than age 80 years. Copyright © 2013 Elsevier Inc. All rights reserved.

Attachment of a Genetically Engineered Antibody to a Carbon Nanotube Transistor for Detection of Prostate Cancer Biomarkers

NASA Astrophysics Data System (ADS)

Lerner, Mitchell; Dailey, Jennifer; Goldsmith, Brett; Robinson, Matthew; Johnson, A. T. Charlie

2011-03-01

We have developed a novel detection method for osteopontin (OPN) by attaching an engineered single chain variable fragment (scFv) protein with high binding affinity for OPN to a carbon nanotube transistor. Osteopontin is a potential new biomarker for prostate cancer; its presence in humans is already associated with several forms of cancer, arthritis, osteoporosis and stress. Prostate cancer is the most commonly diagnosed cancer and second leading cause of cancer deaths among American men and as such represents a major public health issue. Detection of early-stage cancer often results in successful treatment, with long term disease-free survival in 60-90% of patients. Electronic transport measurements are used to detect the presence of OPN in solution at clinically relevant concentrations.

Prostate Cancer Progression and Serum SIBLING (Small Integrin Binding N-linked Glycoprotein) Levels

DTIC Science & Technology

2006-10-01

members include bone sialoprotein (BSP), osteopontin (OPN), dentin matrix protein-1 (DMP1), dentin sialophosphoprotein (DSPP) and matrix extracellular...quantitatively determining the levels of bone sialoprotein (BSP), osteopontin (OPN), and dentin sialophosphoprotein (DSPP). In addition we have a...panels e and f). 6 Figure 1. Serum levels of SIBLINGs in prostate cancer sera. Serum levels of (a) bone sialoprotein (BSP), (c) dentin

A new path in defining light parameters for hair growth: Discovery and modulation of photoreceptors in human hair follicle.

PubMed

Buscone, Serena; Mardaryev, Andrei N; Raafs, Bianca; Bikker, Jan W; Sticht, Carsten; Gretz, Norbert; Farjo, Nilofer; Uzunbajakava, Natallia E; Botchkareva, Natalia V

2017-09-01

Though devices for hair growth based on low levels of light have shown encouraging results, further improvements of their efficacy is impeded by a lack of knowledge on the exact molecular targets that mediate physiological response in skin and hair follicle. The aim of this study was to investigate the expression of selected light-sensitive receptors in the human hair follicle and to study the impact of UV-free blue light on hair growth ex vivo. The expression of Opsin receptors in human skin and hair follicles has been characterized using RT-qPCR and immunofluorescence approaches. The functional significance of Opsin 3 was assessed by silencing its expression in the hair follicle cells followed by a transcriptomic profiling. Proprietary LED-based devices emitting two discrete visible wavelengths were used to access the effects of selected optical parameters on hair growth ex vivo and outer root sheath cells in vitro. The expression of OPN2 (Rhodopsin) and OPN3 (Panopsin, Encephalopsin) was detected in the distinct compartments of skin and anagen hair follicle. Treatment with 3.2 J/cm 2 of blue light with 453 nm central wavelength significantly prolonged anagen phase in hair follicles ex vivo that was correlated with sustained proliferation in the light-treated samples. In contrast, hair follicle treatment with 3.2 J/cm 2 of 689 nm light (red light) did not significantly affect hair growth ex vivo. Silencing of OPN3 in the hair follicle outer root sheath cells resulted in the altered expression of genes involved in the control of proliferation and apoptosis, and abrogated stimulatory effects of blue light (3.2 J/cm 2 ; 453 nm) on proliferation in the outer root sheath cells. We provide the first evidence that (i) OPN2 and OPN3 are expressed in human hair follicle, and (ii) A 453 nm blue light at low radiant exposure exerts a positive effect on hair growth ex vivo, potentially via interaction with OPN3. Lasers Surg. Med. 49:705-718, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Predictive significance of bone sialoprotein and osteopontin for bone metastases in resected Chinese non-small-cell lung cancer patients: a large cohort retrospective study.

PubMed

Zhang, Li; Hou, Xue; Lu, Shun; Rao, Huilan; Hou, Jinghui; Luo, Rongzhen; Huang, He; Zhao, Hongyun; Jian, Hong; Chen, Zhiwei; Liao, Meilin; Wang, Xin

2010-01-01

Bone is one of the most common sites of metastasis in patients with non-small-cell lung cancer (NSCLC). Over-expression of bone sialoprotein (BSP) and osteopontin (OPN) in tumour samples has shown prognostic significance in bone metastasis (BM) of breast and prostate cancer, respectively. However, their importance in BM of NSCLC has not been verified. Therefore, we planned a large cohort retrospective study to investigate the relationship between the expression of these two biomarkers (BSP and OPN) and BM in surgically resected NSCLC patients. 180 completely resected NSCLC patients were included in this study. 40 patients subsequently developed BM. Paraffin-embedded primary tumour tissues of patients were supplied to produce a tissue microarray, and immunohistochemistry method was used for evaluation of the expression of BSP and OPN. Different expressions of these two biomarkers among BM group and non-BM group were estimated by chi(2) test. BM-free survival was analyzed by Kaplan-Meier method. The prognostic impact of clinicopathologic variables and biomarker expression was evaluated by Cox proportional hazards model. BSP expression was associated with BM (p=0.007), whereas OPN expression did not reach statistical significance (p=0.245). Univariate analysis showed that expression of BSP (p=0.010) and N staging (p<0.005) was associated with BM-free survival. Multivariate analyses showed BSP expression (HR=3.322, p=0.003), N staging (HR=1.879, p=0.001), and T staging (HR=1.618, p=0.024) were independent prognostic factors for BM. BSP protein expression in the primary resected NSCLC is strongly associated with BM and could be used to identify high-risk patients. Correlation of OPN protein expression and BM needs further investigation.

Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status

PubMed Central

Wang-Rodriguez, Jessica; Urquidi, Virginia; Rivard, Amber; Goodison, Steve

2003-01-01

Background Our previous characterization of a human breast tumor metastasis model identified several candidate metastasis genes. The expression of osteopontin (OPN) correlated with the metastatic phenotype, whereas thrombospondin-1 (TSP-1) and tyrosinase-related protein-1 (TYRP-1) correlated with the nonmetastatic phenotype of independent MDA-MB-435 cell lines implanted orthotopically into athymic mice. The aim of the present study was to examine the cellular distribution of these molecules in human breast tissue and to determine whether the relative expression level of these three genes is associated with human breast tumor metastasis. Methods Sixty-eight fresh, frozen specimens including 31 primary infiltrating ductal carcinomas, 22 nodal metastases, 10 fibroadenomas, and five normal breast tissues were evaluated for OPN expression, TSP-1 expression and TYRP-1 expression. Immunohistochemistry was performed to monitor the cellular distribution and to qualitatively assess expression. Quantitative analysis was achieved by enrichment of breast epithelial cells using laser-capture microdissection and subsequent real-time, quantitative PCR. Results The epithelial components of the breast tissue were the source of OPN and TSP-1 expression, whereas TYRP-1 was present in both the epithelial and stromal components. Both OPN and TSP-1 expression were significantly higher in malignant epithelial sources over normal and benign epithelial sources, but no difference in expression levels was evident between primary tumors with or without metastases, nor between primary and metastatic carcinomas. Conclusion Elevated expression of OPN and TSP-1 may play a role in the pathogenesis of breast cancer. The multiplex analysis of these molecules may enhance our ability to diagnose and/or prognosticate human breast malignancy. PMID:12927044

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boskey, Adele L., E-mail: boskeya@hss.edu; Christensen, Brian, E-mail: bc@mb.au.dk; Taleb, Hayat, E-mail: Talebh@hss.edu

Highlights: Black-Right-Pointing-Pointer Thrombin-cleaved fragments of milk-osteopontin effect hydroxyapatite formation differently. Black-Right-Pointing-Pointer N- and C-terminal fragments promoted hydroxyapatite formation and growth. Black-Right-Pointing-Pointer A central fragment inhibited hydroxyapatite formation and growth. Black-Right-Pointing-Pointer Binding to collagen or hydroxyapatite seed crystals modified these effects. -- Abstract: The manuscript tests the hypothesis that posttranslational modification of the SIBLING family of proteins in general and osteopontin in particular modify the abilities of these proteins to regulate in vitro hydroxyapatite (HA) formation. Osteopontin has diverse effects on hydroxyapatite (HA) mineral crystallite formation and growth depending on the extent of phosphorylation. We hypothesized that different regions of full-lengthmore » OPN would also have distinct effects on the mineralization process. Thrombin fragmentation of milk OPN (mOPN) was used to test this hypothesis. Three fragments were tested in a de novo HA formation assay; an N-terminal fragment (aa 1-147), a central fragment (aa 148-204) denoted SKK-fragment and a C-terminal fragment (aa 205-262). Compared to intact mOPN the C- and N-terminal fragments behaved comparably, promoting HA formation and growth, but the central SKK-fragment acted as a mineralization inhibitor. In a seeded growth experiment all fragments inhibited mineral proliferation, but the SKK-fragment was the most effective inhibitor. These effects, seen in HA-formation and seeded growth assays in a gelatin gel system and in a pH-stat experiment were lost when the protein or fragments were dephosphorylated. Effects of the fully phosphorylated protein and fragments were also altered in the presence of fibrillar collagen. The diverse effects can be explained in terms of the intrinsically disordered nature of OPN and its fragments which enable them to interact with their multiple partners.« less

Melanopsin Phototransduction Contributes to Light-Evoked Choroidal Expansion and Rod L-Type Calcium Channel Function In Vivo.

PubMed

Berkowitz, Bruce A; Schmidt, Tiffany; Podolsky, Robert H; Roberts, Robin

2016-10-01

In humans, rodents, and pigeons, the dark → light transition signals nonretinal brain tissue to increase choroidal thickness, a major control element of choroidal blood flow, and thus of photoreceptor and retinal pigment epithelium function. However, it is unclear which photopigments in the retina relay the light signal to the brain. Here, we test the hypothesis that melanopsin (Opn4)-regulated phototransduction modulates light-evoked choroidal thickness expansion in mice. Two-month-old C57Bl/6 wild-type (B6), 4- to 5-month-old C57Bl/6/129S6 wild-type (B6 + S6), and 2-month-old melanopsin knockout (Opn4-/-) on a B6 + S6 background were studied. Retinal anatomy was evaluated in vivo by optical coherence tomography and MRI. Choroidal thickness in dark and light were measured by diffusion-weighted MRI. Rod cell L-type calcium channel (LTCC) function in dark and light (manganese-enhanced MRI [MEMRI]) was also measured. Opn4-/- mice did not show the light-evoked expansion of choroidal thickness observed in B6 and B6 + S6 controls. Additionally, Opn4-/- mice had lower than normal rod cell and inner retinal LTCC function in the dark but not in the light. These deficits were not due to structural abnormalities because retinal laminar architecture and thickness, and choroidal thickness in the Opn4-/- mice were similar to controls. First time evidence is provided that melanopsin phototransduction contributes to dark → light control of murine choroidal thickness. The data also highlight a contribution in vivo of melanopsin phototransduction to rod cell and inner retinal depolarization in the dark.

Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder.

PubMed

Kadriu, B; Gold, P W; Luckenbaugh, D A; Lener, M S; Ballard, E D; Niciu, M J; Henter, I D; Park, L T; De Sousa, R T; Yuan, P; Machado-Vieira, R; Zarate, C A

2017-05-30

Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation-the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)-play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 min, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels, and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that, in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness.Molecular Psychiatry advance online publication, 30 May 2017; doi:10.1038/mp.2017.109.

Osteopontin and Other Regulators of Angiogenesis and Fibrogenesis in the Vitreous from Patients with Proliferative Vitreoretinal Disorders

PubMed Central

Abu El-Asrar, Ahmed M.; Imtiaz Nawaz, Mohd; Kangave, Dustan; Siddiquei, Mohammed Mairaj; Geboes, Karel

2012-01-01

The aim of this study was to determine the levels of the angiogenic and fibrogenic factors osteopontin (OPN), high-mobility group box-1 (HMGB1), and connective tissue growth factor (CTGF) and the antiangiogenic and antifibrogenic pigment epithelium-derived factor (PEDF) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and rhegmatogenous retinal detachment with no PVR (RD). Vitreous samples from 48 PDR, 17 PVR and 30 RD patients were studied by enzyme-linked immunosorbent assay. OPN, HMGB1, CTGF, and PEDF levels were significantly higher in PDR patients than in RD patients (P < 0.001; 0.002; <0.001; <0.001, resp.). CTGF and PEDF levels were significantly higher in PVR patients than in RD patients (P < 0.001; 0.004, resp.). Exploratory logistic regression analysis identified significant associations between PDR and high levels of HMGB1, CTGF and PEDF, between PDR with active neovascularization and high levels of CTGF and PEDF, and between PDR with traction retinal detachment and high levels of HMGB1. In patients with PDR, there were significant correlations between the levels of PEDF and the levels of OPN (r = 0.544, P = 0.001), HMGB1 (r = 0.719, P < 0.001), and CTGF (r = 0.715, P < 0.001). In patients with PVR, there were significant correlations between the levels of OPN and the levels of HMGB1 (r = 0.484, P = 0.049) and PEDF (r = 0.559, P = 0.02). Our findings suggest that OPN, HMGB1, and CTGF contribute to the pathogenesis of proliferative vitreoretinal disorders and that increased levels of PEDF may be a response to counterbalance the activity of angiogenic and fibrogenic factors in PDR and PVR. PMID:23055574

Migrated Hem-o-Lok clips in the ureter: a rare cause of recurrent urinary tract infection.

PubMed

Shrivastava, Prashant; Nayak, Brusabhanu; Singh, Prabhjot

2017-02-15

Erosion of surgical materials into the adjacent organs following surgical procedures is a rare complication. Migrations of these surgical materials into the urinary tract like pelvicalyceal system, ureter and bladder have been reported following various urological procedures. We present a case of migrated Hem-o-Lok clips into the ureter following a laparoscopic partial nephrectomy for angiomyolipoma of the left kidney presented with recurrent urinary tract infection. The case was managed with ureteroscopic removal of clips. The patient is asymptomatic on last follow-up. 2017 BMJ Publishing Group Ltd.

[Xanthogranulomatous pyelonephritis in a child with severe malnutrition and recurrent fever].

PubMed

Gramage Tormo, J; Gavilán Martín, C; Atienza Almarcha, T

2015-01-01

Xanthogranulomatous pyelonephritis is a rare inflammatory disease, characterized by replacement of renal parenchyma with granulomatous tissue. Initial clinical presentation includes abdominal pain and constitutional symptoms related to recurrent urinary infections. The microorganisms most commonly involved are Escherichia coli and Proteus mirabilis. Final diagnosis is made by histopathology, and the only curative treatment is total or partial nephrectomy. A recently diagnosed case in our unit is presented, as well as an update on the knowledge of this disease. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Squamous cell carcinoma within a horseshoe kidney with associated renal stones detected by computed tomography and magnetic resonance imaging.

PubMed

Imbriaco, Massimo; Iodice, Delfina; Erra, Paola; Terlizzi, Angela; Di Carlo, Rosanna; Di Vito, Concetta; Imbimbo, Ciro

2011-07-01

We describe a 69-year-old man who came to our observation with a history of persistent left flank abdominal pain, fever for several weeks, and a previous history of passing renal stones. Radiological examinations with computed tomography and magnetic resonance imaging revealed a solid mass within the left side of a horseshoe kidney, with associated large renal stones. The patient subsequently underwent partial left nephrectomy. The final diagnosis was consistent with squamous cell carcinoma arising in a horseshoe kidney, with associated renal stones. Copyright © 2011 Elsevier Inc. All rights reserved.

Postural steadiness and ankle force variability in peripheral neuropathy

PubMed Central

Paxton, Roger J.; Feldman-Kothe, Caitlin; Trabert, Megan K.; Hitchcock, Leah N.; Reiser, Raoul F.; Tracy, Brian L.

2015-01-01

Introduction The purpose was to determine the effect of peripheral neuropathy (PN) on motor output variability for ankle muscles of older adults, and the relation between ankle motor variability and postural stability in PN patients. Methods Older adults with (O-PN) and without PN (O), and young adults (Y) underwent assessment of standing postural stability and ankle muscle force steadiness. Results O-PN displayed impaired ankle muscle force control and postural stability compared with O and Y groups. For O-PN, the amplitude of plantarflexor force fluctuations was moderately correlated with postural stability under no-vision conditions (r = 0.54, P = 0.01). Discussion The correlation of variations in ankle force with postural stability in PN suggests a contribution of ankle muscle dyscontrol to the postural instability that impacts physical function for older adults with PN. PMID:26284897

Laparosopic hand-assisted living donor nephrectomy: the Niguarda experience.

PubMed

Maione, G; Sansalone, C V; Aseni, P; De Roberto, A; Soldano, S; Mangoni, I; Perrino, L; Minetti, E; Civati, G

2005-01-01

Perioperative donor morbidity, a barrier to living organ donation, may be mitigated by the laparoscopic approach. From September 2002 to September 2004, 15 living donors, of ages ranging from 36 to 59 years, underwent laparoscopic nephrectomy. We used a hand-assisted device to increase the safety of the procedure. The average operating time was 200 minutes. The average blood loss was about 100 mL. The patients resumed oral intake and started walking within 1 day. The average postoperative hospital stay was 6 days. Although laparoscopic operating times were longer than those for traditional surgery, we showed benefits to the laparoscopic donor to be less postoperative pain, better cosmesis, shorter recovery time, and faster return to normal activities. We therefore consider laparoscopic nephrectomy a good alternative to traditional surgery for selected patients. Despite a lack of strong evidence, such as large prospective randomized studies, laparoscopic donor nephrectomy is likely to become the gold standard for donor nephrectomy in the near future.

Regulation of osteogenesis of human amniotic mesenchymal stem cells by sodium butyrate.

PubMed

Fan, Xiaoting; Li, Lei; Ye, Zhaoyang; Zhou, Yan; Tan, Wen-Song

2018-04-01

Human amniotic membrane-derived mesenchymal stem cells (hAMSCs) draw great interests for regenerative medicine due to convenient availability and low immunogenicity. However, suboptimal culture conditions limit their application. In recent years, small molecules have proven powerful in regulating stem cell fates and can be applied to stimulate their function. In the present study, the impacts of sodium butyrate (NaBu), a histone deacetylase inhibitor (HDACi), on hAMSCs were investigated. It was shown that NaBu at a low concentration inhibited cell proliferation by arresting cell cycle at G0/G1 rather than inducing apoptosis. When NaBu was supplemented at a concentration of <1.0 mM for 3 days during osteogenic induction, significantly more mineralized nodules were generated and the expression of osteogenesis-related genes (ALP, Runx2, Opn, and Ocn) and proteins (Col1a1, OPN, OCN, Runx2, and TAZ) were both significantly enhanced. However, a higher concentration (1.0 mM) and longer exposure time (14 days) of NaBu showed no such effects, which may be partially attributed to both the increased expression of histone deacetylase 8 (HDAC8) and reduced level of H3K9-Ace, thus leading to the transcriptional inhibition during osteogenesis. Further, it was indicated that ERK might be involved in the stimulatory effects of NaBu. These findings may be helpful to develop an efficient culture process for hAMSCs towards bone regeneration. © 2018 International Federation for Cell Biology.

[Is laparoscopic surgery the technique of choice in nephrectomy?].

PubMed

Ribó, J M; García-Aparicio, L; Julià, V; Tarrado, X; Rovira, J; Morales, L

2003-01-01

Laparoscopic is performed in adults for the treatment of benign renal diseases. It is widely accepted that laparoscopic surgery has more advantages than open surgery in many procedures such as nephrectomy, but there is no further experience in this technique. In pediatric urology laparoscopy has become an accepted approach for varicocele, non palpable testis, bladder augmentation, adrenalectomy and urinary diversion. We report our experience with 25 laparoscopic nephrectomies in children.

The effect of Mastin® on expression of Nrf2 in the rat heart with subtotally nephrectomy chronic Kidney disease model

NASA Astrophysics Data System (ADS)

Nathania, J.; Soetikno, V.

2017-08-01

Chronic kidney disease (CKD) is increasingly prevalent in Indonesia and worldwide. One of the major causes of morbidity and mortality in CKD is the complication of cardiovascular disease. Mastin® is a supplement that is locally produced in Indonesia and is made from extract of mangosteen pericarp, which is reported to have antioxidative, anti-inflammatory, and antitumor properties. The present study aimed to investigate whether Mastin® could improve antioxidant responses in the rat heart during CKD by measuring the expression of nuclear factor erythroid-2-related factor (Nrf)2, a master regulator of antioxidant response elements. RNA was extracted from the heart tissue of three groups of rats: a normal group, a nephrectomy group, and a nephrectomy with Mastin® group. Two-step real-time RT-PCR was then conducted to calculate the relative expression of the Nrf2 gene. Nrf2 expression was markedly decreased in the nephrectomy group vs the normal group, but slightly increas ed in the nephrectomy with Mastin® group vs the nephrectomy group. CKD resulted in impaired activation of the Nrf2 pathway in the rat heart. Although the administration of Mastin® slightly increased Nrf2 expression, it was not enough to confer cardioprotective effects through the Nrf2 pathway.

[Opened vs. laparoscopic radical nephrectomy in renal adenocarcinoma cost comparison].

PubMed

Herranz Amo, F; Subirá Ríos, D; Hernández Fernández, C; Martínez Salamanca, J I; Monzó, J I; Cabello Benavente, R

2006-10-01

To undertake a cost comparison (cost minimization) between transperitoneal laparoscopic and opened nephrectomy in renal adenocarcinoma treatment. Retrospective study on the first 26 patients submitted to LN without intra or postoperative complications in the period 2002-2003, using as control 22 patients treated with ON with the same characteristics and in the same period. Demographic variables were evaluated (age, sex, tumor size, etc.), intraoperative (operative time and fungible material used) and postoperative (length of stay in Postanaesthesic Care Unit, Acute Pain Unit needs and hospital stay). Our Hospital costs plus those imputed during year 2003 to the Urology Service, as well as the cost of fungible material for the same year were applied, carrying out a comparison of costs between both groups. There were no differences between the demographic variables between both groups except in the tumor, bigger size in the opened nephrectomy (p=0,001). Transperitoneal laparoscopic was 29,4% globally more expensive than opened nephrectomy. The transperitoneal laparoscopic intraoperative cost (operating room, anesthesia and fungibles) the exceeded in 151,6% to that of the opened nephrectomy, whereas in the opened nephrectomy the postoperative cost was a 63 % higher than in the transperitoneal laparoscopic cases. Transperitoneal laparoscopic in our Center is more expensive than opened nephrectomy due to a major occupation of operating room and that the specific fungible material used at the surgical act has a very high cost. It would be necessary to drastically reduce surgical time and decrease fungible material expenses, thus transperitoneal laparoscopic procedure could be competitive in our Hospital.

Renal blood flow using arterial spin labelling MRI and calculated filtration fraction in healthy adult kidney donors Pre-nephrectomy and post-nephrectomy.

PubMed

Cutajar, Marica; Hilton, Rachel; Olsburgh, Jonathon; Marks, Stephen D; Thomas, David L; Banks, Tina; Clark, Christopher A; Gordon, Isky

2015-08-01

Renal plasma flow (RPF) (derived from renal blood flow, RBF) and glomerular filtration rate (GFR) allow the determination of the filtration fraction (FF), which may have a role as a non-invasive renal biomarker. This is a hypothesis-generating pilot study assessing the effect of nephrectomy on renal function in healthy kidney donors. Eight living kidney donors underwent arterial spin labelling (ASL) magnetic resonance imaging (MRI) and GFR measurement prior to and 1 year after nephrectomy. Chromium-51 labelled ethylenediamine tetraacetic acid ((51)Cr-EDTA) with multi-blood sampling was undertaken and GFR calculated. The RBF and GFR obtained were used to calculate FF. All donors showed an increase in single kidney GFR of 24 - 75 %, and all but two showed an increase in FF (-7 to +52 %) after nephrectomy. The increase in RBF, and hence RPF, post-nephrectomy was not as great as the increase in GFR in seven out of eight donors. As with any pilot study, the small number of donors and their relatively narrow age range are potential limiting factors. The ability to measure RBF, and hence RPF, non-invasively, coupled with GFR measurement, allows calculation of FF, a biomarker that might provide a sensitive indicator of loss of renal reserve in potential donors. • Non-invasive MRI measured renal blood flow and calculated renal plasma flow. • Effect of nephrectomy on blood flow and filtration in donors is presented. • Calculated filtration fraction may be a useful new kidney biomarker.

Development and Validity of a Silicone Renal Tumor Model for Robotic Partial Nephrectomy Training.

PubMed

Monda, Steven M; Weese, Jonathan R; Anderson, Barrett G; Vetter, Joel M; Venkatesh, Ramakrishna; Du, Kefu; Andriole, Gerald L; Figenshau, Robert S

2018-04-01

To provide a training tool to address the technical challenges of robot-assisted laparoscopic partial nephrectomy, we created silicone renal tumor models using 3-dimensional printed molds of a patient's kidney with a mass. In this study, we assessed the face, content, and construct validity of these models. Surgeons of different training levels completed 4 simulations on silicone renal tumor models. Participants were surveyed on the usefulness and realism of the model as a training tool. Performance was measured using operation-specific metrics, self-reported operative demands (NASA Task Load Index [NASA TLX]), and blinded expert assessment (Global Evaluative Assessment of Robotic Surgeons [GEARS]). Twenty-four participants included attending urologists, endourology fellows, urology residents, and medical students. Post-training surveys of expert participants yielded mean results of 79.2 on the realism of the model's overall feel and 90.2 on the model's overall usefulness for training. Renal artery clamp times and GEARS scores were significantly better in surgeons further in training (P ≤.005 and P ≤.025). Renal artery clamp times, preserved renal parenchyma, positive margins, NASA TLX, and GEARS scores were all found to improve across trials (P <.001, P = .025, P = .024, P ≤.020, and P ≤.006, respectively). Face, content, and construct validity were demonstrated in the use of a silicone renal tumor model in a cohort of surgeons of different training levels. Expert participants deemed the model useful and realistic. Surgeons of higher training levels performed better than less experienced surgeons in various study metrics, and improvements within individuals were observed over sequential trials. Future studies should aim to assess model predictive validity, namely, the association between model performance improvements and improvements in live surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

Laparoscopic Partial Nephrectomy with Diode Laser: A Promising Technique

PubMed Central

Knezevic, Nikola; Maric, Marjan; Grkovic, Marija Topalovic; Krhen, Ivan; Kastelan, Zeljko

2014-01-01

Abstract Objective: The aim of this study was to evaluate application of diode laser in laparoscopic partial nephrectomy (LPN), and to question this technique in terms of ease of tumor excision and reduction of warm ischemia time (WIT). Background data: LPN is the standard operative method for small renal masses. The benefits of LPN are numerous, including preserving renal function and prolonging overall survival. However, reduction of WIT remains main challenge in this operation. In order to shorten WIT, many techniques have been developed, with variable results. Patients and methods: We performed a prospective collection and analysis of health records for patients who were operated on between March 2011 and August 2012. Inclusion criteria were single tumor ≤4 cm, predominant exophytic growth and intraparenchymal depth ≤1.5 cm, with a minimum distance of 5 mm from the urinary collecting system. Results: We operated on 17 patients. Median operative time was 170 min. In all but two patients, we had to perform hilar clamping. Median duration of WIT was 16 min. Pathohistological evaluation revealed clear cell renal cancer and confirmed margins negative for tumor in all cases. Median size of the tumor was 3 cm. Median postoperative hospitalization was 5 days. Average follow up was 11.5 months. There were no intraoperative complications. One postoperative complication was noted: perirenal hematoma. Conclusions: Laser LPN is feasible, and offers the benefit of shorter WIT, with effective tissue coagulation and hemostasis. With operative experience and technical advances, WIT will be reduced or even eliminated, and a solution to some technical difficulties, such as significant smoke production, will be found. PMID:24460067

Use of the Satinsky clamp for hilar clamping during robotic partial nephrectomy: indications, technique, and multi-center outcomes.

PubMed

Abdullah, Newaj; Rahbar, Haider; Barod, Ravi; Dalela, Deepansh; Larson, Jeff; Johnson, Michael; Mass, Alon; Zargar, Homayoun; Kaouk, Jihad; Allaf, Mohamad; Bhayani, Sam; Stifelman, Michael; Rogers, Craig

2017-03-01

A Satinsky clamp may be a backup option for hilar clamping during robotic partial nephrectomy (RPN) if there are challenges with application of bulldog clamps, but there are potential safety concerns. We evaluate outcomes of RPN using Satinsky vs. bulldog clamps, and provide tips for safe use of the Satinsky as a backup option. Using a multi-center database, we identified 1073 patients who underwent RPN between 2006 and 2013, and had information available about method of hilar clamping (bulldog clamp vs. Satinsky clamp). Patient baseline characteristics, tumor features, and perioperative outcomes were compared between the Satinsky and bulldog clamp groups. A Satinsky clamp was used for hilar clamping in 94 (8.8 %) RPN cases, and bulldog clamps were used in 979 (91.2 %) cases. The use of a Satinsky clamp was associated with greater operative time (198 vs. 175 min, p < 0.001), estimated blood loss (EBL, 200 vs. 100 ml, p < 0.001), warm ischemia time (WIT, 20 vs. 19 min, p = 0.036), transfusion rate (12.8 vs. 4.8 %, p = 0.001), and hospital stay (3 vs. 2 days, p < 0.001). Tumor characteristics and number of renal vessels were similar between groups. There were six intraoperative complications in the Satinsky clamp group, but none were directly related to the Satinsky clamp. On multivariable analysis, the use of the Satinsky clamp was not associated with increase in intraoperative or Clavien ≥3 postoperative complications, positive surgical margin rate or percentage change in estimated glomerular filtration rate. A Satinsky clamp can be a backup option for hilar clamping during challenging RPN cases, but requires careful technique, and was rarely necessary.

Crowdsourcing Assessment of Surgeon Dissection of Renal Artery and Vein During Robotic Partial Nephrectomy: A Novel Approach for Quantitative Assessment of Surgical Performance.

PubMed

Powers, Mary K; Boonjindasup, Aaron; Pinsky, Michael; Dorsey, Philip; Maddox, Michael; Su, Li-Ming; Gettman, Matthew; Sundaram, Chandru P; Castle, Erik P; Lee, Jason Y; Lee, Benjamin R

2016-04-01

We sought to describe a methodology of crowdsourcing for obtaining quantitative performance ratings of surgeons performing renal artery and vein dissection of robotic partial nephrectomy (RPN). We sought to compare assessment of technical performance obtained from the crowdsourcers with that of surgical content experts (CE). Our hypothesis is that the crowd can score performances of renal hilar dissection comparably to surgical CE using the Global Evaluative Assessment of Robotic Skills (GEARS). A group of resident and attending robotic surgeons submitted a total of 14 video clips of RPN during hilar dissection. These videos were rated by both crowd and CE for technical skills performance using GEARS. A minimum of 3 CE and 30 Amazon Mechanical Turk crowdworkers evaluated each video with the GEARS scale. Within 13 days, we received ratings of all videos from all CE, and within 11.5 hours, we received 548 GEARS ratings from crowdworkers. Even though CE were exposed to a training module, internal consistency across videos of CE GEARS ratings remained low (ICC = 0.38). Despite this, we found that crowdworker GEARS ratings of videos were highly correlated with CE ratings at both the video level (R = 0.82, p < 0.001) and surgeon level (R = 0.84, p < 0.001). Similarly, crowdworker ratings of the renal artery dissection were highly correlated with expert assessments (R = 0.83, p < 0.001) for the unique surgery-specific assessment question. We conclude that crowdsourced assessment of qualitative performance ratings may be an alternative and/or adjunct to surgical experts' ratings and would provide a rapid scalable solution to triage technical skills.

Assessment of the relationship between renal volume and renal function after minimally-invasive partial nephrectomy: the role of computed tomography and nuclear renal scan.

PubMed

Bertolo, Riccardo; Fiori, Cristian; Piramide, Federico; Amparore, Daniele; Barrera, Monica; Sardo, Diego; Veltri, Andrea; Porpiglia, Francesco

2018-05-14

To evaluate the correlation between the loss of renal function as assessed by Tc99MAG-3 renal scan and the loss of renal volume as calculated by volumetric assessment on CT-scan in patients who underwent minimally-invasive partial nephrectomy (PN). PN prospectively-maintained database was retrospectively queried for patients who underwent minimally-invasive PN (2012-2017) for renal mass

Is near infrared fluorescence imaging using indocyanine green dye useful in robotic partial nephrectomy: a prospective comparative study of 94 patients.

PubMed

Krane, L Spencer; Manny, Theodore B; Hemal, Ashok K

2012-07-01

To compare a consecutive prospective cohort of patients who underwent robotic partial nephrectomy (RPN) with near infrared fluorescence (NIRF) imaging with indocyanine green dye (ICG) with a previous consecutive patient cohort. A total of 47 consecutive patients with renal masses suspicious for malignancy undergoing RPN were given 5-7.5 mg of ICG before hilar clamping or tumor excision. This cohort of patients was compared with 47 immediate previous consecutive patients who had undergone RPN without NIRF real-time imaging using ICG. The intraoperative, perioperative, and postoperative parameters were collected in an institutional review board-approved prospective database. The preoperative demographics and tumor complexity according to the nephrometry or preoperative aspects and dimensions used for an anatomic (PADUA) scores were similar. The mean warm ischemia time was significantly decreased in the ICG group (15 vs 17 minutes, P = .01). The median hospital stay was 2 days in both groups. No significant difference was seen in the positive margin rate (ICG, 6% vs control, 8.5%; P = .69) or observed Clavien grade III-IV complications in these 2 cohorts (ICG, 4% vs control, 15%; P = .07). No adverse events were associated with ICG dye administration. Differential ICG uptake was observed with selective clamping or in patients with cystic tumors, hypofluorescent tumors with exophytic components, and angiomyelolipomas, but these benefits could not be quantified. NIRF-ICG was transiently helpful to identify the vascular anatomy and not helpful at all for endophytic tumors. RPN using NIRF-ICG can be performed safely and effectively. A decreased warm ischemia time in the ICG cohort was observed without specific measured advantages. Differential ICG uptake by different tumors did not lead to significant differences in the positive margin rate. Copyright © 2012 Elsevier Inc. All rights reserved.

Benefits and shortcomings of superselective transarterial embolization of renal tumors before zero ischemia laparoscopic partial nephrectomy.

PubMed

D'Urso, L; Simone, G; Rosso, R; Collura, D; Castelli, E; Giacobbe, A; Muto, G L; Comelli, S; Savio, D; Muto, G

2014-12-01

To report feasibility, safety and effectiveness of "zero-ischemia" laparoscopic partial nephrectomy (LPN) following preoperative superselective transarterial embolization (STE) for clinical T1 renal tumors. We retrospectively reviewed perioperative data of 23 consecutive patients, who underwent STE prior LPN between March 2010 and November 2012 for incidental clinical T1 renal mass. STE was performed by two experienced radiologists the day before surgery. Surgical procedures were performed in extended flank position, transperitoneally, by a single surgeon. Mean patients age was 68 years (range 56-74), mean tumor size was 3.5 cm (range 2.2-6.3 cm). STE was successfully completed in 16 patients 12-15 h before surgery. In 4 cases STE failed to provide a complete occlusion of all feeding arteries, while in 3 cases the ischemic area was larger than expected. LPN was successfully completed in all patients but one where open conversion was necessary; a "zero-ischemia" approach was performed in 19/23 patients (82.6%) while hilar clamp was necessary in 4 cases, with a mean warm-ischemia time of 14.8 min (range 5-22). Mean operative time was 123 min (range 115-130) and mean intraoperative blood loss was 250 mL (range 20-450). No patient experienced postoperative acute renal failure and no patient developed new onset IV stage chronic kidney disease at 1-yr follow-up. STE is a viable option to perform "zero-ischemia" LPN at beginning of learning curve; however, hilar clamp was necessary to achieve a relatively blood-less field in 17.4% of cases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Robotic partial nephrectomy - Evaluation of the impact of case mix on the procedural learning curve.

PubMed

Roman, A; Ahmed, K; Challacombe, B

2016-05-01

Although Robotic partial nephrectomy (RPN) is an emerging technique for the management of small renal masses, this approach is technically demanding. To date, there is limited data on the nature and progression of the learning curve in RPN. To analyse the impact of case mix on the RPN LC and to model the learning curve. The records of the first 100 RPN performed, were analysed at our institution that were carried out by a single surgeon (B.C) (June 2010-December 2013). Cases were split based on their Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score into the following groups: 6-7, 8-9 and >10. Using a split group (20 patients in each group) and incremental analysis, the mean, the curve of best fit and R(2) values were calculated for each group. Of 100 patients (F:28, M:72), the mean age was 56.4 ± 11.9 years. The number of patients in each PADUA score groups: 6-7, 8-9 and >10 were 61, 32 and 7 respectively. An increase in incidence of more complex cases throughout the cohort was evident within the 8-9 group (2010: 1 case, 2013: 16 cases). The learning process did not significantly affect the proxies used to assess surgical proficiency in this study (operative time and warm ischaemia time). Case difficulty is an important parameter that should be considered when evaluating procedural learning curves. There is not one well fitting model that can be used to model the learning curve. With increasing experience, clinicians tend to operate on more difficult cases. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Surgical planning and manual image fusion based on 3D model facilitate laparoscopic partial nephrectomy for intrarenal tumors.

PubMed

Chen, Yuanbo; Li, Hulin; Wu, Dingtao; Bi, Keming; Liu, Chunxiao

2014-12-01

Construction of three-dimensional (3D) model of renal tumor facilitated surgical planning and imaging guidance of manual image fusion in laparoscopic partial nephrectomy (LPN) for intrarenal tumors. Fifteen patients with intrarenal tumors underwent LPN between January and December 2012. Computed tomography-based reconstruction of the 3D models of renal tumors was performed using Mimics 12.1 software. Surgical planning was performed through morphometry and multi-angle visual views of the tumor model. Two-step manual image fusion superimposed 3D model images onto 2D laparoscopic images. The image fusion was verified by intraoperative ultrasound. Imaging-guided laparoscopic hilar clamping and tumor excision was performed. Manual fusion time, patient demographics, surgical details, and postoperative treatment parameters were analyzed. The reconstructed 3D tumor models accurately represented the patient's physiological anatomical landmarks. The surgical planning markers were marked successfully. Manual image fusion was flexible and feasible with fusion time of 6 min (5-7 min). All surgeries were completed laparoscopically. The median tumor excision time was 5.4 min (3.5-10 min), whereas the median warm ischemia time was 25.5 min (16-32 min). Twelve patients (80 %) demonstrated renal cell carcinoma on final pathology, and all surgical margins were negative. No tumor recurrence was detected after a media follow-up of 1 year (3-15 months). The surgical planning and two-step manual image fusion based on 3D model of renal tumor facilitated visible-imaging-guided tumor resection with negative margin in LPN for intrarenal tumor. It is promising and moves us one step closer to imaging-guided surgery.

Robotic partial nephrectomy with intracorporeal renal hypothermia using ice slush.

PubMed

Kaouk, Jihad H; Samarasekera, Dinesh; Krishnan, Jayram; Autorino, Riccardo; Acka, Oktay; Brando, Luis Felipe; Laydner, Humberto; Zargar, Homayoun

2014-09-01

To outline our technique for intracorporeal cooling with ice slush during robotic partial nephrectomy (RPN), with real-time parenchymal temperature monitoring. Eleven consecutive patients with enhancing solid renal masses suitable for treatment with RPN between September 2013 and January 2014 were included in the analysis. Institutional review board approval and informed consent were obtained. Preoperative patient characteristics, intraoperative surgical parameters including patient body temperature and ipsilateral kidney temperature with real-time monitoring, and short-term functional outcomes were analyzed. Median age was 55 years (range, 39-75 years) and American Society of Anesthesiologists score was 3 (range, 2-4). Median tumor size was 4 cm (range, 2.3-7.1) and RENAL nephrometry score was 9 (range, 5-11). One patient had a solitary kidney. During cooling, the lowest median renal parenchymal temperature was 17.05°C (range, 11°C-26°C) and cold ischemia time was 27.17 minutes (range, 18-49 minutes). Median time to latest postoperative estimated glomerular filtration rate was 12 days (range, 2-30 days). Median glomerular filtration rate preservation was 81% (range, 47.9%-126%). There was one positive margin. There were no postoperative complications, and no patients experienced a prolonged ileus. The limitations of this study include a small number of patients and short-term follow-up. RPN with renal hypothermia using intracorporeal ice slush is technically feasible. Our simplified method of introducing the ice slush was free of complications and highly reproducible. The use of a needle temperature probe allowed us to monitor in real time cooling of the renal parenchyma. Copyright © 2014 Elsevier Inc. All rights reserved.

Impact of preoperative calculation of nephron volume loss on future of partial nephrectomy techniques; planning a strategic roadmap for improving functional preservation and securing oncological safety.

PubMed

Rha, Koon H; Abdel Raheem, Ali; Park, Sung Y; Kim, Kwang H; Kim, Hyung J; Koo, Kyo C; Choi, Young D; Jung, Byung H; Lee, Sang K; Lee, Won K; Krishnan, Jayram; Shin, Tae Y; Cho, Jin-Seon

2017-11-01

To assess the correlation of the resected and ischaemic volume (RAIV), which is a preoperatively calculated volume of nephron loss, with the amount of postoperative renal function (PRF) decline after minimally invasive partial nephrectomy (PN) in a multi-institutional dataset. We identified 348 patients from March 2005 to December 2013 at six institutions. Data on all cases of laparoscopic (n = 85) and robot-assisted PN (n = 263) performed were retrospectively gathered. Univariable and multivariable linear regression analyses were used to identify the associations between various time points of PRF and the RAIV, as a continuous variable. The mean (sd) RAIV was 24.2 (29.2) cm 3 . The mean preoperative estimated glomerular filtration rate (eGFR) and the eGFRs at postoperative day 1, 6 and 36 months after PN were 91.0 and 76.8, 80.2 and 87.7 mL/min/1.73 m 2 , respectively. In multivariable linear regression analysis, the amount of decline in PRF at follow-up was significantly correlated with the RAIV (β 0.261, 0.165, 0.260 at postoperative day 1, 6 and 36 months after PN, respectively). This study has the limitation of its retrospective nature. Preoperatively calculated RAIV significantly correlates with the amount of decline in PRF during long-term follow-up. The RAIV could lead our research to the level of prediction of the amount of PRF decline after PN and thus would be appropriate for assessing the technical advantages of emerging techniques. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Impact of warm ischaemia time on postoperative renal function after partial nephrectomy for clinical T1 renal cell carcinoma: a propensity score-matched study.

PubMed

Lee, Hakmin; Song, Byung D; Byun, Seok-Soo; Lee, Sang E; Hong, Sung K

2018-01-01

To analyse the effect of prolonged warm ischaemia time (WIT) on long-term renal function after partial nephrectomy (PN), as controversy still exists as to whether prolonged WIT adversely affects the incidence of chronic kidney disease (CKD) after PN. We reviewed data from 1816 patients who underwent PN for a clinical T1 renal tumour. The propensity scores for prolonged WIT were calculated with the shorter WIT group (<30 min) matched to the longer WIT group (≥30 min) in a 2:1 ratio. Multivariate analysis was used to determine independent predictors for occurrence of postoperative CKD [defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m 2 ] and major renal function deterioration (MRFD; defined as an eGFR decrease of ≥25% postoperatively). After propensity score matching, there was no significant difference in CKD-free survival between the two WIT groups (P = 0.787). Furthermore, longer WIT did not show any significant associations with postoperative CKD-free survival [hazard ratio (HR) 1.002, 95% confidence interval (CI) 0.989-1.015; P = 0.765) and MRFD-free survival (HR 1.014, 95% CI 1.000-1.028; P = 0.055). From further subgroup analyses using more specific WIT thresholds (≤20, 21-30, 31-40, 41-50, ≥50 min) and status of preoperative CKD, no significant differences were noted in CKD and MRFD-free survival amongst the subgroups (all P > 0.05). Prolonged WIT was not associated with increased incidence of CKD or MRFD after PN. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

A retrospective analysis of laparoscopic partial nephrectomy with segmental renal artery clamping and factors that predict postoperative renal function.

PubMed

Li, Pu; Qin, Chao; Cao, Qiang; Li, Jie; Lv, Qiang; Meng, Xiaoxin; Ju, Xiaobing; Tang, Lijun; Shao, Pengfei

2016-10-01

To evaluate the feasibility and efficiency of laparoscopic partial nephrectomy (LPN) with segmental renal artery clamping, and to analyse the factors affecting postoperative renal function. We conducted a retrospective analysis of 466 consecutive patients undergoing LPN using main renal artery clamping (group A, n = 152) or segmental artery clamping (group B, n = 314) between September 2007 and July 2015 in our department. Blood loss, operating time, warm ischaemia time (WIT) and renal function were compared between groups. Univariable and multivariable linear regression analyses were applied to assess the correlations of selected variables with postoperative glomerular filtration rate (GFR) reduction. Volumetric data and estimated GFR of a subset of 60 patients in group B were compared with GFR to evaluate the correlation between these functional variables and preserved renal function after LPN. The novel technique slightly increased operating time, WIT and intra-operative blood loss (P < 0.001), while it provided better postoperative renal function (P < 0.001) compared with the conventional technique. The blocking method and tumour characteristics were independent factors affecting GFR reduction, while WIT was not an independent factor. Correlation analysis showed that estimated GFR presented better correlation with GFR compared with kidney volume (R(2) = 0.794 cf. R(2) = 0.199) in predicting renal function after LPN. LPN with segmental artery clamping minimizes warm ischaemia injury and provides better early postoperative renal function compared with clamping the main renal artery. Kidney volume has a significantly inferior role compared with eGFR in predicting preserved renal function. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Usefulness of the Ice-Cream Cone Pattern in Computed Tomography for Prediction of Angiomyolipoma in Patients With a Small Renal Mass

PubMed Central

Kim, Kwang Ho; Yun, Bu Hyeon; Hwang, In Sang; Hwang, Eu Chang; Kang, Taek Won; Kwon, Dong Deuk; Park, Kwangsung; Kim, Jin Woong

2013-01-01

Purpose A morphologic contour method for assessing an exophytic renal mass as benign versus malignant on the basis of the shape of the interface with the renal parenchyma was recently developed. We investigated the usefulness of this morphologic contour method for predicting angiomyolipoma (AML) in patients who underwent partial nephrectomy for small renal masses (SRMs). Materials and Methods From January 2004 to March 2013, among 197 patients who underwent partial nephrectomy for suspicious renal cell carcinoma (RCC), the medical records of 153 patients with tumors (AML or RCC) ≤3 cm in diameter were retrospectively reviewed. Patient characteristics including age, gender, type of surgery, size and location of tumor, pathologic results, and specific findings of the imaging study ("ice-cream cone" shape) were compared between the AML and RCC groups. Results AML was diagnosed in 18 patients and RCC was diagnosed in 135 patients. Gender (p=0.001), tumor size (p=0.032), and presence of the ice-cream cone shape (p=0.001) showed statistically significant differences between the AML group and the RCC group. In the multivariate logistic regression analysis, female gender (odds ratio [OR], 5.20; 95% confidence interval [CI], 1.45 to 18.57; p=0.011), tumor size (OR, 0.34; 95% CI, 0.12 to 0.92; p=0.034), and presence of the ice-cream cone shape (OR, 18.12; 95% CI, 4.97 to 66.06; p=0.001) were predictors of AML. Conclusions This study confirmed a high incidence of AML in females. Also, the ice-cream cone shape and small tumor size were significant predictors of AML in SRMs. These finding could be beneficial for counseling patients with SRMs. PMID:23956824

Oncologic outcomes of patients with positive surgical margin after partial nephrectomy: a 25-year single institution experience.

PubMed

Petros, Firas G; Metcalfe, Michael J; Yu, Kai-Jie; Keskin, Sarp K; Fellman, Bryan M; Chang, Courtney M; Gu, Cindy; Tamboli, Pheroze; Matin, Surena F; Karam, Jose A; Wood, Christopher G

2018-07-01

To evaluate oncologic outcomes and management of patients with microscopic positive surgical margin (PSM) after partial nephrectomy (PN) for renal cell carcinoma (RCC). We reviewed our database to identify patients who underwent PN between 1990 and 2015 for RCC and had PSM on final pathology. A 1:3 matching was performed to a negative surgical margin (NSM) cohort. Kaplan-Meier method and log-rank test were used to estimate survival and differences in outcomes, respectively. Cox proportional hazards models were conducted to estimate the Hazards ratio. A total of 2297 patients underwent PN at our institution, of which 1863 (81%) had RCC. Microscopic PSM was found in 34 (1.8%) RCC patients who were matched to 100 patients with NSM. Of these 34 patients, local recurrence (n = 4), distant kidney recurrences (n = 4), and metastases (n = 5) developed during a median follow-up of 62 months. Bilateral tumors/tumors in a solitary kidney (n = 12/13, 92%), and multifocal tumors (n = 7/13, 54%) were found in patients who developed recurrence/metastasis. PSM patients were at a higher risk of shorter overall survival (p = 0.001), local recurrence-free survival (p = 0.003), distant recurrence-free survival (p = 0.032) and metastasis-free survival (p = 0.018). There was statistically significant association between PSM and bilateral tumors, prior treated RCC at presentation and higher nephrometry score in multivariable model. There was a low rate of microscopic PSM in our large cohort of patients undergoing PN despite tumor complexity. Higher nephrometry score, bilateral tumors, and prior treated RCC independently predicted PSM which showed worse survival, recurrence and metastasis compared to patients with NSM.

Functional Recovery From Extended Warm Ischemia Associated With Partial Nephrectomy.

PubMed

Zhang, Zhiling; Zhao, Juping; Velet, Lily; Ercole, Cesar E; Remer, Erick M; Mir, Carme M; Li, Jianbo; Takagi, Toshio; Demirjian, Sevag; Campbell, Steven C

2016-01-01

To evaluate the impact of extended warm ischemia on incidence of acute kidney injury (AKI) and ultimate functional recovery after partial nephrectomy (PN), incorporating rigorous control for loss of parenchymal mass, and embedded within comparison to cohorts of patients managed with hypothermia or limited warm ischemia. From 2007 to 2014, 277 patients managed with PN had appropriate studies to evaluate changes in function/mass specifically within the operated kidney. Recovery from ischemia was defined as %function saved/%parenchymal mass saved. AKI was based on global renal function and defined as a ≥1.5-fold increase in serum creatinine above the preoperative level. Hypothermia was utilized in 112 patients (median = 27 minutes) and warm ischemia in 165 (median = 21 minutes). AKI strongly correlated with solitary kidney (P < .001) and duration (P < .001) but not type (P = .49) of ischemia. Median recovery from ischemia in the operated kidney was 100% (interquartile range [IQR] = 88%-109%) for cold ischemia, with 6 (5%) noted to have <80% recovery from ischemia. For the warm ischemia group, median recovery from ischemia was 91% (IQR = 82%-101%, P < .001 compared with hypothermia), and 34 (21%) had recovery from ischemia <80% (P < .001). For warm ischemia subgrouped by duration <25 minutes (n = 114), 25-35 minutes (n = 35), and >35 minutes (n = 16), median recovery from ischemia was 92% (IQR = 86%-100%), 90% (IQR = 78%-104%), and 91% (IQR = 80%-96%), respectively (P = .77). Our results suggest that AKI after PN correlates with duration but not with type of ischemia. However, subsequent recovery, which ultimately defines the new baseline glomerular filtration rate, is most reliable with hypothermia. However, most patients undergoing PN with warm ischemia still recover relatively strongly from ischemia, even if extended to 35-45 minutes. Copyright © 2015 Elsevier Inc. All rights reserved.

Predictors of postoperative decline in estimated glomerular filtration rate in patients undergoing robotic partial nephrectomy.

PubMed

Wiener, Scott; Kiziloz, Halil; Dorin, Ryan P; Finnegan, Kyle; Shichman, Steven S; Meraney, Anoop

2014-07-01

To identify prognostic indicators of estimated glomerular filtration rate (eGFR) following robotic partial nephrectomy (RPN). In a retrospective study of RPN patients, we examined data describing age, gender, eGFR, body mass index (BMI), tumor size (TS), length of stay, and estimated blood loss (EBL). Changes in eGFR (i.e., renal function trajectory [RFT]) and chronic kidney disease (CKD) stage shift were analyzed with mixed model linear and logistic regression analyses, Chi-squared, and t-tests. Changes in eGFR (RFT) were determined in 122 patients at baseline and at 6- and 12-month follow-up visits. Mean age, TS, and Charlson comorbidity index (CCI) were 62±11 years, 3±1.2 cm, and 4.8±1.8, respectively. The pre- and postoperative eGFR was lower in patients >60 years. Preoperative eGFR was unrelated to gender, BMI>30 kg/m(2), histopathology, nuclear grade, and TS. Univariate analyses determined that age, BMI>30, EBL>200 mL, CCI>5, and TS were associated with greater declines in eGFR. Reduced eGFR was also associated with warm ischemia time ≥22 minutes, while age was associated with a ≥1 worsening of British CKD classification. Using multivariate analysis, only age was significantly associated with a decline in eGFR, which was greater in patients with a normal preoperative eGFR. Patient age, BMI>30, EBL>200 mL, CCI>5, and TS were predictors of greater postoperative declines in eGFR. Although a decline in eGFR was proportionally greater in low stage CKD, postoperative changes are associated with advancing age.

Single-port laparoscopic and robotic partial nephrectomy.

PubMed

Kaouk, Jihad H; Goel, Raj K

2009-05-01

Partial nephrectomy (PN) for small renal masses provides effective oncologic outcomes. Single-port laparoscopic (SPL) and robotic surgeries are evolving approaches to advance minimally invasive surgery. To determine the feasibility of laparoscopic and robotic single-port PN. Since 2007, evaluation of patients undergoing SPL and single-port robotic (SPR) PN at a primary referral center was performed. Patients with small, solitary, exophytic-enhancing renal masses were selected. Patients with a solitary kidney, endophytic or hilar tumors, and previous abdominal and/or kidney surgery were excluded. Perioperative and pathologic data were entered prospectively into an institutional review board (IRB)-approved database. Tumor location determined either an open Hasson transperitoneal or retroperitoneal approach. A single multichannel port or Triport provided intra-abdominal access. The Harmonic Scalpel was used for tumor excision under normal renal perfusion. The da Vinci surgical robot was used for SPR cases. Patient demographics, perioperative, hematologic, and pathologic data as well as pain assessment using the Visual Analog Pain Scale (VAPS) were assessed. A total of seven patients underwent single-port PN (SPL=5, SPR=2). One patient with a right anterior upper-pole mass required conversion from SPL to standard laparoscopy following tumor excision because of intraoperative bleeding. Pathology revealed six lesions compatible with renal cell carcinoma (RCC) and one benign cyst. One negative frozen section came back focally positive on final histopathology. All other surgical margins were negative. A mean difference of 3.0+/-2.0 g/dl in hemoglobin was noted in all patients. Minimal pain was noted at discharge following both laparoscopic and robotic single-port surgery (VAPS=1.7+/-1.2 vs 1+/-0.5/10). SPL and SPR PN is feasible for select exophytic tumors. Robotics may improve surgical capabilities during single-port surgery.

Da Vinci Xi and Si platforms have equivalent perioperative outcomes during robot-assisted partial nephrectomy: preliminary experience.

PubMed

Abdel Raheem, Ali; Sheikh, Abulhasan; Kim, Dae Keun; Alatawi, Atalla; Alabdulaali, Ibrahim; Han, Woong Kyu; Choi, Young Deuk; Rha, Koon Ho

2017-03-01

The aims of this study were to compare the perioperative outcomes of da Vinci Xi to Si during robotic-assisted partial nephrectomy (RAPN) and to discuss the feasibility of our novel port placement scheme for the da Vinci Xi platform, to overcome the existing kinetic and technical difficulties we faced with the linear port placement in patients with a small body habitus. A retrospective data analysis of patients who underwent RPN using da Vinci Xi (n = 18) was carried out. The outcomes of the Xi group were compared with the Si group (n = 18) selected using a case-matched methodology. For da Vinci Xi, we applied the universal linear port placement in 12 patients and our modified port placement in the remaining 6 patients. The Xi group had a shorter mean docking time of 17.8 ± 2.6 min compared to the Si group of 20.5 ± 2.1 min (p = 0.002); otherwise, no significant difference was present with regard to the remaining perioperative variables (p > 0.05). The modified Xi port placement had a shorter mean console time of 70.8 ± 9.7 min compared to the universal linear port placement of 89.3 ± 17.2 min (p = 0.03). Moreover, it provided a broader field of vision with excellent robotic arms movement, minimizing collisions and allowing an easier and comfortable surgical assist. Da Vinci Xi appears to be feasible and safe during RPN with similar outcomes to Si. The novel Xi port placement makes surgery easier in patients with low BMI.

The Piezo Actuator-Driven Pulsed Water Jet System for Minimizing Renal Damage after Off-Clamp Laparoscopic Partial Nephrectomy.

PubMed

Kamiyama, Yoshihiro; Yamashita, Shinichi; Nakagawa, Atsuhiro; Fujii, Shinji; Mitsuzuka, Koji; Kaiho, Yasuhiro; Ito, Akihiro; Abe, Takaaki; Tominaga, Teiji; Arai, Yoichi

2017-09-01

In the setting of partial nephrectomy (PN) for renal cell carcinoma, postoperative renal dysfunction might be caused by surgical procedure. The aim of this study was to clarify the technical safety and renal damage after off-clamp laparoscopic PN (LPN) with a piezo actuator-driven pulsed water jet (ADPJ) system. Eight swine underwent off-clamp LPN with this surgical device, while off-clamp open PN was also performed with radio knife or soft coagulation. The length of the removed kidney was 40 mm, and the renal parenchyma was dissected until the renal calyx became clearly visible. The degree of renal degeneration from the resection surface was compared by Hematoxylin-Eosin staining and immunostaining for 1-methyladenosine, a sensitive marker for the ischemic tissue damage. The mRNA levels of neutrophil gelatinase-associated lipocalin (Ngal), a biomarker for acute kidney injury, were measured by quantitative real-time PCR. Off-clamp LPN with ADPJ system was successfully performed while preserving fine blood vessels and the renal calix with little bleeding. In contrast to other devices, the resection surface obtained with the ADPJ system showed only marginal degree of ischemic changes. Indeed, the expression level of Ngal mRNA was lower in the resection surface obtained with the ADPJ system than that with soft coagulation (p = 0.02). Furthermore, using the excised specimens of renal cell carcinoma, we measured the breaking strength at each site of the human kidney, suggesting the applicability of this ADPJ to clinical trials. In conclusion, off-clamp LPN with the ADPJ system could be safely performed with attenuated renal damage.

The effect of nephrectomy on Klotho, FGF-23 and bone metabolism.

PubMed

Kakareko, Katarzyna; Rydzewska-Rosolowska, Alicja; Brzosko, Szymon; Gozdzikiewicz-Lapinska, Joanna; Koc-Zorawska, Ewa; Samocik, Pawel; Kozlowski, Robert; Mysliwiec, Michal; Naumnik, Beata; Hryszko, Tomasz

2017-04-01

Increased concentration of fibroblast growth factor 23 (FGF-23) and decreased levels of soluble Klotho (sKL) are linked to negative clinical outcomes among patients with chronic kidney disease and acute kidney injury. Therefore, it is reasonable to hypothesize that GFR reduction caused by nephrectomy might alter mineral metabolism and induces adverse consequences. Whether nephrectomy due to urological indications causes derangements in FGF-23 and sKL has not been studied. The aim of the study was to evaluate the effect of acute GFR decline due to unilateral nephrectomy on bone metabolism, FGF-23 and sKL levels. This is a prospective, single-centre observational study of patients undergoing nephrectomy due to urological indications. Levels of C-terminal FGF-23 (c-FGF-23), sKL and bone turnover markers [β-crosslaps (CTX), bone-specific alkaline phosphatase (bALP) and tartrate-resistant acid phosphatase 5b (TRAP 5b)] were measured before and after surgery (5 ± 2 days). Twenty-nine patients were studied (14 females, age 63.0 ± 11.6, eGFR 87.3 ± 19.2 ml/min/1.73 m 2 ). After surgery, eGFR significantly declined (p < 0.0001). Nephrectomy significantly decreased sKL level [709.8 (599.9-831.2) vs. 583.0 (411.7-752.6) pg/ml, p < 0.001] and did not change c-FGF-23 concentration [70.5 (49.8-103.3) vs. 77.1 (60.5-109.1) RU/ml, p = 0.9]. Simultaneously, alterations in bone turnover markers were observed. Serum concentration of CTX increased [0.49 (0.4-0.64) vs. 0.59 (0.46-0.85) ng/ml, p = 0.001], while bALP and TRAP 5b decreased [23.6 (18.8-31.4) vs. 17.9 (15.0-22.0) U/l, p < 0.0001 and 3.3 (3.0-3.7) vs. 2.8 (2.3-3.2) U/l, p < 0.001, respectively]. Nephrectomy among patients with preserved renal function before surgery does not increase c-FGF-23 but reduces sKL. Moreover, nephrectomy results in derangements in bone turnover markers in short-term follow-up. These changes may participate in pathogenesis of bone disease after nephrectomy.

Does robotic assistance confer an economic benefit during laparoscopic radical nephrectomy?

PubMed

Yang, David Y; Monn, M Francesca; Bahler, Clinton D; Sundaram, Chandru P

2014-09-01

While robotic assisted radical nephrectomy is safe with outcomes and complication rates comparable to those of the pure laparoscopic approach, there is little evidence of an economic or clinical benefit. From the 2009 to 2011 Nationwide Inpatient Sample database we identified patients 18 years old or older who underwent radical nephrectomy for primary renal malignancy. Robotic assisted and laparoscopic techniques were noted. Patients treated with the open technique and those with evidence of metastatic disease were excluded from analysis. Descriptive statistics were performed using the chi-square and Mann-Whitney tests, and the Student t-test. Multiple linear regression was done to examine factors associated with increased hospital costs and charges. We identified 24,312 radical nephrectomy cases for study inclusion, of which 7,787 (32%) were performed robotically. There was no demographic difference between robotic assisted and pure laparoscopic radical nephrectomy cases. Median total charges were $47,036 vs $38,068 for robotic assisted vs laparoscopic surgery (p <0.001). Median total hospital costs for robotic assisted surgery were $15,149 compared to $11,735 for laparoscopic surgery (p <0.001). There was no difference in perioperative complications or the incidence of death. Compared to the laparoscopic approach robotic assistance conferred an estimated $4,565 and $11,267 increase in hospital costs and charges, respectively, when adjusted for adapted Charlson comorbidity index score, perioperative complications and length of stay (p <0.001). Robotic assisted radical nephrectomy results in increased medical expense without improving patient morbidity. Assuming surgeon proficiency with pure laparoscopy, robotic technology should be reserved primarily for complex surgeries requiring reconstruction. Traditional laparoscopic techniques should continue to be used for routine radical nephrectomy. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Correlation between CO2 storage at the last minute of gas insufflation and area of retroperitoneal lacuna during retroperitoneal laparoscopic radical nephrectomy.

PubMed

Hu, Jian-Jun; Liu, Ya-Hua; Yu, Chan-Juan; Jialielihan, Nuerbolati

2016-07-22

Adequate operation interspace is the premise of laparoscopy, and carbon dioxide (CO2) was an ideal gas for forming lacuna. A retroperitoneal space is used to form operation interspace in retroperitoneal laparoscopic radical nephrectomy by making ballooning, and the retroperitoneal space has no relative complete and airtight serous membrane, therefore CO2 absorption may be greater in retroperitoneal than transperitoneal laparoscopic radical nephrectomy. Excess CO2 absorption may induce hypercapnemia and further cause physiopathological change of respiratory and circulatory system. Therefore, exact evaluation of amount of CO2 which is eliminated from body via minute ventilation is important during retroperitoneal laparoscopic radical nephrectomy. The aim of the paper is to study the correlation between CO2 storage at the last minute of gas insufflation and area of retroperitoneal lacuna during retroperitoneal laparoscopic radical nephrectomy. Forty ASA I/II patients undergoing retroperitoneal laparoscopic radical nephrectomy were enrolled. CO2 storage at the last minute of gas insufflation and area of a retroperitoneal lacuna were observed. Linear correlation and regression were performed to determine the correlation between them. There was positive correlation between CO2 storage at the last minute of gas insufflation and area of retroperitoneal lacuna (r = 0.880, P = 0.000), and the equation of linear regression was y = -83.097 + 0.925x (R(2) = 0.780, t = 11.610, P = 0.000). Amount of CO2 which is eliminated from body via mechanical ventilation could be calculated by measuring the area of retroperitoneal lacuna during retroperitoneal laparoscopic radical nephrectomy, and an anesthetist should be aware of the size of lacuna to predict high CO2 storage at the last minute of gas insufflation.

Effectiveness of deep versus moderate muscle relaxation during laparoscopic donor nephrectomy in enhancing postoperative recovery: study protocol for a randomized controlled study.

PubMed

Bruintjes, Moira H D; Braat, Andries E; Dahan, Albert; Scheffer, Gert-Jan; Hilbrands, Luuk B; d'Ancona, Frank C H; Donders, Rogier A R T; van Laarhoven, Cornelis J H M; Warlé, Michiel C

2017-03-04

Postoperative recovery after live donor nephrectomy is largely determined by the consequences of postoperative pain and analgesia consumptions. The use of deep neuromuscular blockade has been shown to reduce postoperative pain scores after laparoscopic surgery. In this study, we will investigate whether deep neuromuscular blockade also improves the early quality of recovery after live donor nephrectomy. The RELAX-study is a phase IV, multicenter, double-blinded, randomized controlled trial, in which 96 patients, scheduled for living donor nephrectomy, will be randomized into two groups: one with deep and one with moderate neuromuscular blockade. Deep neuromuscular blockade is defined as a post-tetanic count of 1-2. Our primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 24 h after extubation. This study is, to our knowledge, the first randomized study to assess the effectiveness of deep neuromuscular blockade during laparoscopic donor nephrectomy in enhancing postoperative recovery. The study findings may also be applicable for other laparoscopic procedures. clinicaltrials.gov, NCT02838134 . Registered on 29 June 2016.

Cone opsins, colour blindness and cone dystrophy: Genotype-phenotype correlations.

PubMed

Gardner, J C; Michaelides, M; Hardcastle, A J

2016-05-25

X-linked cone photoreceptor disorders caused by mutations in the OPN1LW (L) and OPN1MW (M) cone opsin genes on chromosome Xq28 include a range of conditions from mild stable red-green colour vision deficiencies to severe cone dystrophies causing progressive loss of vision and blindness. Advances in molecular genotyping and functional analyses of causative variants, combined with deep retinal phenotyping, are unravelling genetic mechanisms underlying the variability of cone opsin disorders.

Osteopontin splice variants expression is involved on docetaxel resistance in PC3 prostate cancer cells.

PubMed

Nakamura, K D M; Tilli, T M; Wanderley, J L; Palumbo, A; Mattos, R M; Ferreira, A C; Klumb, C E; Nasciutti, L E; Gimba, E R

2016-02-01

Osteopontin (OPN) is a phosphoprotein that activates several aspects of tumor progression. Alternative splicing of the OPN primary transcript generates three splicing isoforms, OPNa, OPNb and OPNc. In this report, we investigated some cellular mechanisms by which OPN splice variants could mediate PC3 prostate cancer (PCa) cell survival and growth in response to docetaxel (DXT)-induced cell death. Cell survival before and after DXT treatment was analyzed by phase-contrast microscopy and crystal-violet staining assays. Quantitative real-time PCR and immunocytochemical staining assays were used to evaluate the putative involvement of epithelial-mesenchymal transition (EMT) and OPN isoforms on mediating PC3 cell survival. Upon DXT treatment, PC3 cells overexpressing OPNb or OPNc isoforms showed higher cell densities, compared to cells overexpressing OPNa and controls. Notably, cells overexpressing OPNb or OPNc isoforms showed a downregulated pattern of EMT epithelial cell markers, while mesenchymal markers were mostly upregulated in these experimental conditions. We concluded that OPNc or OPNb overexpression in PC3 cells can mediate resistance and cell survival features in response to DXT-induced cell death. Our data also provide evidence the EMT program could be one of the molecular mechanisms mediating survival in OPNb- or OPNc-overexpressing cells in response to DXT treatment. These data could further contribute to a better understanding of the mechanisms by which PCa cells acquire resistance to DXT treatment.

Nephrectomy (Kidney Removal)

MedlinePlus

... nephrectomy is needed because of other kidney diseases. Kidney function Most people have two kidneys — fist-sized ... and the disease that prompted the surgery? Monitoring kidney function Most people can function well with only ...

[Renal cell carcinoma producing erythrocytosis due to inappropriate production of erythropoietin].

PubMed

Villanueva-Gimeno, M M; Vicario-Bermúdez, J M; Fonseca-López, Ch; Caballero-Castro, J P; Zabala-López, S I; Sánchez-Elipe, M A; González-Gómez, N

2013-01-01

Erythrocytosis, or polycythaemia, is an increase, in absolute terms, of the erythrocyte mass. The most common solid tumour related to this phenomenon is renal cell carcinoma, which can produce erythrocytosis by increasing erythropoietin production. About 30% of symptomatic renal cell carcinomas are diagnosed due to the appearance of a paraneoplastic syndrome. Polycythaemia is one of these. Surgery, (radical or partial nephrectomy), is the treatment of choice in renal cell carcinoma and helps to keep the erythrocytosis situation under control. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Dynamics of Heat Shock Protein 70 Serum Levels As a Predictor of Clinical Response in Non-Small-Cell Lung Cancer and Correlation with the Hypoxia-Related Marker Osteopontin

PubMed Central

Ostheimer, Christian; Gunther, Sophie; Bache, Matthias; Vordermark, Dirk; Multhoff, Gabriele

2017-01-01

Hypoxia mediates resistance to radio(chemo)therapy (RT) by stimulating the synthesis of hypoxia-related genes, such as osteopontin (OPN) and stress proteins, including the major stress-inducible heat shock protein 70 (Hsp70). Apart from its intracellular localization, Hsp70 is also present on the plasma membrane of viable tumor cells that actively release it in lipid vesicles with biophysical characteristics of exosomes. Exosomal Hsp70 contributes to radioresistance while Hsp70 derived from dying tumor cells can serve as a stimulator of immune cells. Given these opposing traits of extracellular Hsp70 and the unsatisfactory outcome of locally advanced lung tumors, we investigated the role of Hsp70 in the plasma of patients with advanced, non-metastasized non-small-cell lung cancer (NSCLC) before (T1) and 4–6 weeks after RT (T2) in relation to OPN as potential biomarkers for clinical response. Plasma levels of Hsp70 correlate with those of OPN at T1, and high OPN levels are significantly associated with a decreased overall survival (OS). Due to a therapy-induced reduction in viable tumor mass after RT Hsp70 plasma levels dropped significantly at T2 (p = 0.016). However, with respect to the immunostimulatory capacity of Hsp70 derived from dying tumor cells, patients with higher post-therapeutic Hsp70 levels showed a significantly better response to RT (p = 0.034) than those with lower levels at T2. In summary, high OPN plasma levels at T1 are indicative for poor OS, whereas elevated post-therapeutic Hsp70 plasma levels together with a drop of Hsp70 between T1 and T2, successfully predict favorable responses to RT. Monitoring the dynamics of Hsp70 in NSCLC patients before and after RT can provide additional predictive information for clinical outcome and therefore might allow a more rapid therapy adaptation. PMID:29093708

Optimized Negative Staining: a High-throughput Protocol for Examining Small and Asymmetric Protein Structure by Electron Microscopy

DOE PAGES

Rames, Matthew; Yu, Yadong; Ren, Gang

2014-08-15

Structural determination of proteins is rather challenging for proteins with molecular masses between 40 - 200 kDa. Considering that more than half of natural proteins have a molecular mass between 40 - 200 kDa, a robust and high-throughput method with a nanometer resolution capability is needed. Negative staining (NS) electron microscopy (EM) is an easy, rapid, and qualitative approach which has frequently been used in research laboratories to examine protein structure and protein-protein interactions. Unfortunately, conventional NS protocols often generate structural artifacts on proteins, especially with lipoproteins that usually form presenting rouleaux artifacts. By using images of lipoproteins from cryo-electronmore » microscopy (cryo-EM) as a standard, the key parameters in NS specimen preparation conditions were recently screened and reported as the optimized NS protocol (OpNS), a modified conventional NS protocol. Artifacts like rouleaux can be greatly limited by OpNS, additionally providing high contrast along with reasonably high-resolution (near 1 nm) images of small and asymmetric proteins. These high-resolution and high contrast images are even favorable for an individual protein (a single object, no average) 3D reconstruction, such as a 160 kDa antibody, through the method of electron tomography. Moreover, OpNS can be a high-throughput tool to examine hundreds of samples of small proteins. For example, the previously published mechanism of 53 kDa cholesteryl ester transfer protein (CETP) involved the screening and imaging of hundreds of samples. Considering cryo-EM rarely successfully images proteins less than 200 kDa has yet to publish any study involving screening over one hundred sample conditions, it is fair to call OpNS a high-throughput method for studying small proteins. Hopefully the OpNS protocol presented here can be a useful tool to push the boundaries of EM and accelerate EM studies into small protein structure, dynamics and mechanisms.« less

Osterix Controls Cementoblast Differentiation through Downregulation of Wnt-signaling via Enhancing DKK1 Expression

PubMed Central

Cao, Zhengguo; Liu, Rubing; Zhang, Hua; Liao, Haiqing; Zhang, Yufeng; Hinton, Robert J.; Feng, Jian Q.

2015-01-01

Osterix (Osx), a transcriptional factor essential for osteogenesis, is also critical for in vivo cellular cementum formation. However, the molecular mechanism by which Osx regulates cementoblasts is largely unknown. In this study, we initially demonstrated that overexpression of Osx in a cementoblast cell line upregulated the expression of markers vital to cementogenesis such as osteopontin (OPN), osteocalcin (OCN), and bone sialoprotein (BSP) at both mRNA and protein levels, and enhanced alkaline phosphatase (ALP) activity. Unexpectedly, we demonstrated a sharp increase in the expression of DKK1 (a potent canonical Wnt antagonist), and a great reduction in protein levels of β-catenin and its nuclear translocation by overexpression of Osx. Further, transient transfection of Osx reduced protein levels of TCF1 (a target transcription factor of β-catenin), which were partially reversed by an addition of DKK1. We also demonstrated that activation of canonical Wnt signaling by LiCl or Wnt3a significantly enhanced levels of TCF1 and suppressed the expression of OPN, OCN, and BSP, as well as ALP activity and formation of extracellular mineralized nodules. Importantly, we confirmed that there were a sharp reduction in DKK1 and a concurrent increase in β-catenin in Osx cKO mice (crossing between the Osx loxP and 2.3 Col 1-Cre lines), in agreement with the in vitro data. Thus, we conclude that the key role of Osx in control of cementoblast proliferation and differentiation is to maintain a low level of Wnt-β-catenin via direct up-regulation of DKK1. PMID:25678852

Temporary targeted renal blood flow interruption using a reverse thermosensitive polymer to facilitate bloodless partial nephrectomy: a swine survival study.

PubMed

Harty, Niall J; Laskey, Daniel H; Moinzadeh, Alireza; Flacke, Sebastian; Benn, James A; Villani, Rosanna; Kalra, Aarti; Libertino, John A; Madras, Peter N

2012-09-01

What's known on the subject? and What does the study add? Lumagel™ is a reverse thermosensitive polymer (RTP) that has previously been described in the literature as providing temporary vascular occlusion to allow for bloodless partial nephrectomy (PN) while maintaining blood flow to the untargeted portion of the kidney. At body temperature, Lumagel™ has the consistency of a viscous gel but upon cooling rapidly converts to a liquid state and does not reconstitute thereafter. This property has allowed for it to be used in situations requiring temporary vascular occlusion. Previous experience with similar RTPs in coronary arteries proved successful, with no detectable adverse events. We have previously described our technique for temporary vascular occlusion of the main renal artery, as well as segmental and sub-segmental renal branches, to allow for bloodless PN in either an open or minimally invasive approach. These experiments were performed in the acute setting. This study is a two-armed survival trial to assess whether this RTP is as safe as hilar clamping for bloodless PN. Surviving animals showed normal growth after using the RTP, absence of toxicity, no organ dysfunction, and no pathological changes attributable to the RTP. We conclude that Lumagel™ is as safe as conventional PN with hilar clamping, while adding the advantage of uninterrupted perfusion during renal resection. To examine whether randomly selected regions of the kidney could undergo temporary flow interruption with a reverse thermosensitive polymer (RTP), Lumagel™ (Pluromed, Inc., Woburn, MA, USA), followed by partial nephrectomy (PN), without adding risks beyond those encountered in the same procedure with the use of hilar clamping. A two-armed (RTP vs hilar clamp), 6-week swine survival study was performed. Four swine underwent PN using hilar clamps, while six underwent PN with flow interruption using the RTP. The RTP, administered angiographically, was used for intraluminal occlusion of segmental or subsegmental arteries and was compared with main renal artery clamping with hilar clamps. The resection site was randomized for each swine. Laboratory studies were performed preoperatively, and at weeks 1, 3 and 6. Before killing the swine, repeat angiography was performed with emphasis on the site of previous flow interruption. Gross and microscopic examination of kidney, liver, lung, heart, skeletal muscle was later performed, and the vessel that had supported the previous plug was examined. All animals survived. No abnormal chemistry or haematology results were encountered over the 6 weeks. There were no surgical complications in either group. Using angiography we found 100% patency of vessels that had been occluded with the polymer 6 weeks previously for PN. The only gross or microscopic abnormalities were related to the renal resection and scar formation, and were similar in the two groups. Targeted flow interruption with the RTP added no additional risk to PN while allowing bloodless resection and uninterrupted flow to untargeted renal tissue. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.

Cranial pole nephrectomy in the pig model: anatomic analysis of arterial injuries in tridimensional endocasts.

PubMed

Pereira-Sampaio, Marco A; Henry, Robert W; Favorito, Luciano A; Sampaio, Francisco J B

2012-06-01

To assess the intrarenal arteries injuries after cranial pole nephrectomy in a pig model to compare these findings with those in humans. Polyester resin was injected through the ureter and the renal artery to make three-dimensional casts of 61 pig kidneys. The cranial pole of the kidneys was sectioned at four different sites before the solidification of the resin, and the casts were examined for arterial damage. Section performed through the hilus (15 kidneys): The cranial division of the renal artery was sectioned in two (13.33%) cases, the ventral branch of the cranial division of the renal artery was sectioned in 13 (86.7%) cases, and the dorsal branch of the cranial division of the renal artery was sectioned in 11 (73.34%) cases. Section at 0.5 cm cranial to the hilus (16 kidneys): The cranial division of the renal artery was sectioned in 1 (6.25%) case, the ventral branch of the cranial division of the renal artery was sectioned in 14 (87.5%) cases, and the dorsal branch of the cranial division of the renal artery was sectioned in 13 (81.25%) cases. Section at 1.0 cm cranial to the hilus (15 kidneys): The ventral branch of the cranial division of the renal artery was sectioned in five (33.33%) cases, and the dorsal branch of the cranial division of the renal artery was injured in five (33.33%) cases. Section at 1.5 cm cranial to the hilus (15 kidneys): No lesions were found in the main arteries, only in the interlobular branches. As previously demonstrated in humans, sections at 1.0 cm or more cranially to the hilus in pigs also showed a significant decrease in damage to the major intrarenal arteries. Therefore, as regards arterial damage, the pig kidney is a useful model for partial nephrectomy in the cranial (upper) pole.

Factors associated with renal function compensation after donor nephrectomy.

PubMed

Burballa, Carla; Crespo, Marta; Redondo-Pachón, Dolores; Pérez-Sáez, María José; Arias-Cabrales, Carlos; Mir, Marisa; Francés, Albert; Fumadó, Lluís; Cecchini, Lluís; Pascual, Julio

2018-05-14

Kidney transplant donors lose 50% of their renal mass after nephrectomy. The remaining kidney compensates for this loss and it is estimated that 70% of the baseline renal function prior to donation is recovered. Factors associated with post-donation renal compensation are not well understood. Retrospective study of 66 consecutive kidney donors (mean age 48.8 years, 74.2% women). We analysed the potential factors associated with the compensatory mechanisms of the remaining kidney by comparing donors according to their renal compensation rate (RCR) (Group A, infra-compensation [<70%]; Group B, normal compensation [>70%]). We compared Group A (n=38) and group B (n=28). Predictors for RCR>70% were higher baseline creatinine (A vs B: 0.73±0.14 vs 0.82±0.11; P=.03) and a lower baseline glomerular filtration rate (GFR), estimated both by MDRD-4 (A vs B: 97.7±18.8 vs 78.6±9.6ml/min; P<.001) and CKD-EPI (A vs B: 101.7±15 vs. 88.3±11.7ml/min; P≤.001). Age, gender, smoking, hypertension and GFR measured by Tc-DTPA did not show any correlation with the RCR. The multivariate analysis confirmed baseline estimated glomerular filtration rate (eGFR) to be a predictor of compensation: the higher the baseline eGFR, the lower the likelihood of >70% compensation (MDRD-4, OR=0.94 [95% CI 0.8-0.9], P=.01). The compensation rate decreased by 0.4% (P<.001) and 0.3% (P=.006) for every ml/min increase in baseline eGFR estimated by MDRD-4 and CKD-EPI, respectively. One year after living donor nephrectomy, the remaining kidney partially compensates baseline renal function. In our experience, baseline eGFR is inversely proportional to the one-year renal compensation rate. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Renal artery aneurysm in hand-assisted laparoscopic donor nephrectomy: case report.

PubMed

Maciel, R F; Branco, A J; Branco, A W; Guterres, J C; Silva, A E; Ramos, L B; Rost, C; Vieira, C A; Cicogna, P E S; Daudt, C A; Deboni, L M; Vieira, M A; Luz, H A; Vieira, J A

2003-12-01

We report a living donor who underwent laparoscopic nephrectomy using a hand-assisted device (HALD). At preoperative arteriography the donor showed a renal artery aneurysm. The patient was a 37-year-old female, 166 cm height, white, weighing 87 kg, HLA identical to the recipient. HALD was indicated due to the better visualization of renal pedicle and greater security in an obese patient. Renal artery aneurysm is a rare condition, with many possible complications. The method proved to be adequate and safe for donor nephrectomy, despite a renal artery aneurysm.

Robot-assisted partial nephrectomy vs laparoscopic cryoablation for the small renal mass: redefining the minimally invasive 'gold standard'.

PubMed

Emara, Amr M; Kommu, Sashi S; Hindley, Richard G; Barber, Neil J

2014-01-01

To identify differences between the ablative and extirpative minimally invasive techniques of laparoscopic cryoablation (LC) and robot-assisted laparoscopic partial nephrectomy (RPN), respectively, in treating small renal tumours in terms of safety, peri-operative morbidity and early oncological outcomes. Between June 2008 and April 2012 56 patients underwent LC and from October 2010 to April 2012, 47 patients underwent RPN using the Da Vinci robotic platform (Intuitive Surgical, Sunnyvale, CA, USA). Data on intra-operative, postoperative and oncological outcomes were collected prospectively, and were analysed and compared for both groups. The median patient ages were 69 and 60 for the LC and RPN groups, respectively (P < 0.05). There was no significant difference in disease stage, but there was a significant difference in tumour size, with patients in the RPN group having larger tumours. The mean operating times were 146 and 159 min for the LC and RPN groups, respectively (P = 0.094) and the mean blood loss was 47 and 94 mL for the LC and the RPN groups, respectively (P = 0.251). The median length of hospital stay (1 day) was the same for both groups and the mean warm ischaemia time was 23 min in the RPN group. The marginal change in preoperative and 6-week postoperative renal function was recorded: the mean postoperative increase in serum creatinine was 5.4 mmol/L in the LC group and 9.2 mmol/L in the RPN group. Of the 47 patients in the RPN group, two (4.3%) were converted to laparoscopic radical nephrectomy because of difficulty in controlling bleeding during hilar dissection. Only two patients (3.6%) had recurrence in the LC group, both of whom were treated with re-cryoablation. A total of 5.4% of patients in the LC and 4.3% in the RPN group had Clavien grade I postoperative complications, one patient in the LC group had a Clavien grade II complication, while 1.8 and 4.3% of patients had Clavien IIIb in the LC and RPN groups, respectively. Our data confirm that LC is a successful, minimally invasive and safe treatment option for the management of small renal tumours, but the apparently similar characteristics of RPN suggest that an increasing proportion of patients, whatever their age or medical comorbidities, may be reasonably offered a robot-assisted extirpative procedure with the likely benefit of lower risk of local recurrence and need for retreatment. © 2013 The Authors. BJU International © 2013 BJU International.

The impact of seat belts and airbags on high grade renal injuries and nephrectomy rate in motor vehicle collisions.

PubMed

Bjurlin, Marc A; Fantus, Richard Jacob; Fantus, Richard Joseph; Mellett, Michele M; Villines, Dana

2014-10-01

Motor vehicle collisions are the most common cause of blunt genitourinary trauma. We compared renal injuries with no protective device to those with seat belts and/or airbags using NTDB. Our primary end point was a decrease in high grade (grades III-V) renal injuries with a secondary end point of a nephrectomy rate reduction. The NTDB research data sets for hospital admission years 2010, 2011 and 2012 were queried for motor vehicle collision occupants with renal injury. Subjects were stratified by protective device and airbag deployment. The AIS was converted to AAST renal injury grade and nephrectomy rates were evaluated. Intergroup comparisons were analyzed for renal injury grades, nephrectomy, length of stay and mortality using the chi-square test or 1-way ANOVA. The relative risk reduction of protective devices was determined. A review of 466,028 motor vehicle collisions revealed a total of 3,846 renal injuries. Injured occupants without a protective device had a higher rate of high grade renal injuries (45.1%) than those with seat belts (39.9%, p = 0.008), airbags (42.3%, p = 0.317) and seat belts plus airbags (34.7%, p <0.001). Seat belts (20.0%), airbags (10.5%) and seat belts plus airbags (13.3%, each p <0.001) decreased the nephrectomy rate compared to no protective device (56.2%). The combination of seatbelts and airbags also decreased total hospital length of stay (p <0.001) and intensive care unit days (p = 0.005). The relative risk reductions of high grade renal injuries (23.1%) and nephrectomy (39.9%) were highest for combined protective devices. Occupants of motor vehicle collisions with protective devices show decreased rates of high grade renal injury and nephrectomy. Reduction appears most pronounced with the combination of seat belts and airbags. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Impact of Seat belts and Airbags on High Grade Renal Injuries and Nephrectomy Rates in Motor Vehicle Collisions

PubMed Central

Bjurlin, Marc A; Fantus, Richard J.; Mellett, Michele M.; Fantus, Richard J.; Villines, Dana

2015-01-01

Purpose Motor vehicle collisions (MVCs) are the most common cause of blunt genitourinary trauma. We compared renal injuries with no protective device to those with seat belts and/or airbags utilizing the National Trauma Data Bank (NTDB). Our primary endpoint was a reduction in high-grade renal injuries (grades III-V) with a secondary endpoint of reduction in nephrectomy rate. Materials and Methods The NTDB research datasets, admission year 2010, 2011, and 2012, were queried for MVC occupants with renal injury. Subjects were stratified by protective device and airbag deployment. Abbreviated Injury Score was converted to American Association for the Surgery of Trauma renal injury grade and nephrectomy rates were evaluated. Intergroup comparisons were analyzed for renal injury grades, nephrectomy, length of stay, and mortality with chi-square or one-way ANOVA. Protective device relative risk reduction was determined. Results A review of 466,028 MVCs revealed 3,846 renal injuries. Injured occupants without a protective device had a higher rate of high grade renal injury (45.1%) compared to those with seat belts (39.9%, p=0.008), airbags (42.3%, p=0.317), and seat belts with airbags (34.7%, p<0.001). Seat belts (20.0%, p<0.001), airbags (10.5% p<0.001), and seat belts with airbags (13.3%, p<0.001) reduced the rate of nephrectomy compared to no protective device (56.2%). The combination of seatbelts and airbags also reduced total hospital length of stay (p<0.001) and ICU days (p=0.005). Relative risk reduction of high-grade renal injuries (23.1%) and nephrectomy (39.9%) were highest for combined protective devices. Conclusions Occupants of MVCs with protective devices have reduced rates of high-grade renal injury and nephrectomy. Reduction appears most pronounced with the combination of seat belts and airbags. PMID:24846798

Osteopontin expression and clinicopathologic correlation of oral hyperplastic reactive lesions: An institutional 6-year retrospective study.

PubMed

Narwal, Anjali; Bala, Shashi

2017-01-01

Reactive proliferations of oral cavity comprise pyogenic granuloma (PG), fibrous hyperplasia (FH), peripheral ossifying fibroma (POF), and peripheral giant-cell granuloma (PGCG). They often pose diagnostic challenges due to their overlapping clinical and histopathological features. This study was conducted to determine the frequency and clinicopathological correlation of reactive hyperplastic lesions in the oral cavity reported in our institute and compared it with other previous studies. Further evaluation of osteopontin (OPN) expression in normal gingival tissue and different types of focal reactive lesions was also done. Data of all reactive hyperplasias were retrieved, reviewed, and analyzed for age, gender, clinical presentation, and site of location. Presence and distribution of OPN were assessed using immunohistochemistry in these reactive lesions. Two hundred and forty-eight reactive lesions were comprised of FH (38%), PG (23%), POF (13%), and PGCG (7%). FH was more common in males (55%) whereas other reactive lesions were more in females (68%-73%). The most frequently involved site was gingiva (59%), and most common clinical presentation was sessile growth on gingiva. OPN expression was minimal in normal gingiva. Few cases of FH, PG, and all cases of POF showed positivity for OPN in inflammatory cells, stromal cells, extracellular matrix, and in calcifications. Reactive hyperplastic lesions of oral cavity are mucosal responses to chronic low-grade irritation caused by plaque, calculus, and any other irritant. It is helpful to know their frequency and presentation as their early identification enables accurate patient evaluation and management.

Euarchontan Opsin Variation Brings New Focus to Primate Origins

PubMed Central

Melin, Amanda D.; Wells, Konstans; Moritz, Gillian L.; Kistler, Logan; Orkin, Joseph D.; Timm, Robert M.; Bernard, Henry; Lakim, Maklarin B.; Perry, George H.; Kawamura, Shoji; Dominy, Nathaniel J.

2016-01-01

Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination. PMID:26739880

Midkine Increases Diagnostic Yield in AFP Negative and NASH-Related Hepatocellular Carcinoma

PubMed Central

Vongsuvanh, Roslyn; van der Poorten, David; Iseli, Tristan; Strasser, Simone I.; McCaughan, Geoffrey W.; George, Jacob

2016-01-01

Robust biomarkers for population-level hepatocellular carcinoma (HCC) surveillance are lacking. We compared serum midkine (MDK), dickkopf-1 (DKK1), osteopontin (OPN) and AFP for HCC diagnosis in 86 HCC patients matched to 86 cirrhotics, 86 with chronic liver disease (CLD) and 86 healthy controls (HC). Based on the performance of each biomarker, we assessed a separate longitudinal cohort of 28 HCC patients, at and before cancer diagnosis. Serum levels of MDK and OPN were higher in HCC patients compared to cirrhosis, CLD and HC groups. DKK1 was not different between cases and controls. More than half of HCC patients had normal AFP. In this AFP-negative HCC cohort, 59.18% (n = 29/49) had elevated MDK, applying the optimal cut-off of 0.44 ng/ml. Using AFP ≥ 20 IU/ml or MDK ≥ 0.44 ng/ml, a significantly greater number (76.7%; n = 66/86) of HCC cases were detected. The area under the receiver operating curve for MDK was superior to AFP and OPN in NASH-HCC diagnosis. In the longitudinal cohort, MDK was elevated in 15/28 (54%) of HCC patients at diagnosis, of whom 67% had elevated MDK 6 months prior. Conclusion: AFP and MDK have a complementary role in HCC detection. MDK increases the diagnostic yield in AFP-negative HCC and has greater diagnostic performance than AFP, OPN and DKK-1 in the diagnosis of NASH-HCC. Additionally, MDK has a promising role in the pre-clinical diagnosis of HCC. PMID:27219517

[Salidroside inhibits hypoxia-induced phenotypic modulation of corpus cavernosum smooth muscle cells in vitro].

PubMed

Chen, Gang; Huang, Xiao-Jun; Lü, Bo-Dong; Chen, Shi-Tao; Zhang, Shi-Geng; Yang, Ke-Bing

2013-08-01

To explore the effects of salidroside on the phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMC) in hypoxic SD rats. CCSMCs were cultured in vitro and identified by immunohistochemistry. The cells were divided into six groups: normal control (21% O2), hypoxia (1% O2), hypoxia + salidroside 1 mg/L, hypoxia + salidroside 3 mg/L, hypoxia + salidroside 5 mg/L and hypoxia + PGE1 0.4 microg/L, and then cultured for 48 hours. The relative expressions of alpha-actin and osteopontin (OPN) in each group were determined by RT-PCR. The in vitro cultured CCSMCs grew well, with anti-alpha-smooth muscle actin monoclonal antibodies immunohistochemically positive. The relative expression of alpha-actin was markedly decreased while that of OPN remarkably increased in the hypoxia group as compared with the normal control group (P < 0.01). The hypoxia + salidroside 5 mg/L group showed a significantly higher expression of alpha-actin and lower expression of OPN than the hypoxia group (P < 0.01), but exhibited no significant differences from the hypoxia + PGE group (P > 0.05). Hypoxia can reduce the relative expression level of alpha-actin and increase that of OPN in the CCSMCs of SD rats, namely, induce their phenotypic modulation from the contraction to the non-contraction type. Salidroside can restrain hypoxia-induced phenotypic modulation of CCSMCs, and its inhibitory effect at 5 mg/L is similar to that of PGE1.

Nectin-like molecule 1 inhibits the migration and invasion of U251 glioma cells by regulating the expression of an extracellular matrix protein osteopontin.

PubMed

Yin, Bin; Li, Ke-han; An, Tai; Chen, Tao; Peng, Xiao-zhong

2010-06-01

To investigate the molecular mechanism of nectin-like molecule 1 (NECL1) inhibiting the migration and invasion of U251 glioma cells. We infected U251 glioma cells with adeno-nectin-like molecule 1 (Ad-NECL1) or empty adenovirus (Ad). Transwell and wound healing assays were performed to observe the migration of U251 cells incubated with the cell supernatant from Ad-NECL1 or Ad infected U251 cells. DNA microarray was applied to screen the gene expression profile after the restoration of NECL1 in U251 glioma cell lines. The differential expression of osteopontin (OPN), a gene related to migration and invasion, was further analyzed with semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry. The restoration of NECL1 inhibited migration of U251 cells significantly (P<0.05). Altogether 195 genes were found differentially expressed by microarray, in which 175 were up-regulated and 20 down-regulated, including 9 extracellular matrix proteins involved in the migration of cells. Both mRNA and protein expressions of OPN, the most markedly reduced extracellular matrix protein, were found decreased in U251 cells after restoration of NECL1. Immunohistochemical assay also detected an increase of OPN in glioma tissues, related with the progressing of malignant grade. A link might exist between NECL1 and the extracellular matrix protein OPN in inhibiting the migration and invasion of U251 glioma cells.

[Bilateral nephrectomy in patients with end-stage renal failure and chronic active pyelonephritis].

PubMed

Lysenko, M A; Vtorenko, V I; Trushkin, R N; Lubennikov, A E; Sysoev, A M; Sokolov, A A

2016-02-01

This study analyzed the results of bilateral nephrectomy in 14 patients with end-stage renal disease (ESRD) and chronic active pyelonephritis. Seven patients had urosepsis, and 10 patients had a purulent form of pyelonephritis, which was one-sided in 7 of them. In the early postoperative period, on average, after 9.3 days, 9 patients died. Statistically significant risk factors for death were: chronic hemodialysis, long-term antibiotic therapy, and existing sepsis. Intraoperative complications and postoperative morbidity were not significantly associated with death. The study results imply the need of differentiated approach to bilateral nephrectomy in patients with ESRD and risk factors for fatal outcome. It must be performed on the strong indications since the intervention does not lead to eradication of sepsis. It is advisable to perform "preventive, sanation" bilateral nephrectomy in the "cold period" in patients at risk for developing urosepsis.

Perioperative Events and Complications in Minimally Invasive Live Donor Nephrectomy: A Systematic Review and Meta-Analysis.

PubMed

Kortram, Kirsten; Ijzermans, Jan N M; Dor, Frank J M F

2016-11-01

Minimally invasive live donor nephrectomy has become a fully implemented and accepted procedure. Donors have to be well educated about all risks and details during the informed consent process. For this to be successful, more information regarding short-term outcome is necessary. A literature search was performed; all studies discussing short-term complications after minimally invasive live donor nephrectomy were included. Outcomes evaluated were intraoperative and postoperative complications, conversions, operative and warm ischemia times, blood loss, length of hospital stay, pain score, convalescence, quality of life, and costs. One hundred ninety articles were included in the systematic review, 41 in the meta-analysis. Conversion rate was 1.1%. Intraoperative complication rate was 2.3%, mainly bleeding (1.5%). Postoperative complications occurred in 7.3% of donors, including infectious complications (2.6%), of which mainly wound infection (1.6%) and bleeding (1.0%). Reported mortality rate was 0.01%. All minimally invasive techniques were comparable with regard to complication or conversion rate. The used techniques for minimally invasive live donor nephrectomy are safe and associated with low complication rates and minimal risk of mortality. These data may be helpful to develop a standardized, donor-tailored informed consent procedure for live donor nephrectomy.

Preoperative fiducial coil placement facilitates robot-assisted laparoscopic excision of retroperitoneal small solitary metastasis of kidney cancer.

PubMed

Agrawal, Vineet; Sharma, Ashwani; Wu, Guan

2014-11-01

Image-guided fiducial markers are being used in surgery, especially in spine and breast surgery, and radiotherapy, allowing localization of tumor sites precisely. We report a case of fiducial coil use in a man undergoing a robot-assisted laparoscopic resection of a metastatic nodule under the ipsilateral diaphragm after robot-assisted partial nephrectomy performed 2 years ago for a left upper pole renal tumor. The fiducial coil facilitated the localization of the lesion, which would otherwise have been challenging because of its small size and location. In addition, the fiducial coil was helpful to avoid cutting into the lesion directly. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinically Non-Metastatic Renal Cell Carcinoma With Sarcomatoid Dedifferentiation: Natural History and Outcomes after Surgical Resection with Curative Intent

PubMed Central

Merrill, Megan M.; Wood, Christopher G.; Tannir, Nizar M.; Slack, Rebecca S.; Babaian, Kara N.; Jonasch, Eric; Pagliaro, Lance C.; Compton, Zachary; Tamboli, Pheroze; Sircar, Kanishka; Pisters, Louis L.; Matin, Surena F.; Karam, Jose A.

2015-01-01

Purpose Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive malignancy associated with a poor prognosis. While existing literature focuses on patients presenting with metastatic disease, characteristics and outcomes for patients with localized disease are not well described. We aimed to evaluate post-nephrectomy characteristics, outcomes, and predictors of survival in patients with sRCC who presented with clinically localized disease. Patients and Methods An IRB-approved review from 1986–2011 identified 77 patients who presented with clinically localized disease, underwent nephrectomy and had sRCC in their primary kidney tumor. Clinical and pathologic variables were captured for each patient. Overall survival (OS) and recurrence-free survival (RFS) were calculated for all patients and those who had no evidence of disease (NED) following nephrectomy, respectively. Comparisons were made with categorical groupings in proportional hazards regression models for univariable and multivariable analyses. Results OS for the entire cohort (N=77) at 2 years was 50%. A total of 56 (77%) patients of the 73 who were NED following nephrectomy experienced a recurrence, with a median time to recurrence of 26.2 months. On multivariable analysis, tumor stage, pathologically positive lymph nodes, and year of nephrectomy were significant predictors of both OS and RFS. Limitations include the retrospective nature of this study and relatively small sample size. Conclusions Long-term survival for patients with sRCC, even in clinically localized disease is poor. Aggressive surveillance of those who are NED following nephrectomy is essential and further prospective studies evaluating the benefit of adjuvant systemic therapies in this cohort are warranted. PMID:25700975

Renal structure and function evaluation of rats from dams that received increased sodium intake during pregnancy and lactation submitted or not to 5/6 nephrectomy.

PubMed

Marin, Evelyn Cristina Santana; Balbi, Ana Paula Coelho; Francescato, Heloísa Della Coletta; Alves da Silva, Cleonice Giovanini; Costa, Roberto Silva; Coimbra, Terezila M

2008-01-01

Adult rats submitted to perinatal salt overload presented renin-angiotensin system (RAS) functional disturbances. The RAS contributes to the renal development and renal damage in a 5/6 nephrectomy model. The aim of the present study was to analyze the renal structure and function of offspring from dams that received a high-salt intake during pregnancy and lactation. We also evaluated the influence of the prenatal high-salt intake on the evolution of 5/6 nephrectomy in adult rats. A total of 111 sixty-day-old rat pups from dams that received saline or water during pregnancy and lactation were submitted to 5/6 nephrectomy (nephrectomized) or to a sham operation (sham). The animals were killed 120 days after surgery, and the kidneys were removed for immunohistochemical and histological analysis. Systolic blood pressure (SBP), albuminuria, and glomerular filtration rate (GFR) were evaluated. Increased SBP, albuminuria, and decreased GFR were observed in the rats from dams submitted to high-sodium intake before surgery. However, there was no difference in these parameters between the groups after the 5/6 nephrectomy. The scores for tubulointerstitial lesions and glomerulosclerosis were higher in the rats from the sham saline group compared to the same age control rats, but there was no difference in the histological findings between the groups of nephrectomized rats. In conclusion, our data showed that the high-salt intake during pregnancy and lactation in rats leads to structural changes in the kidney of adult offspring. However, the progression of the renal lesions after 5/6 nephrectomy was similar in both groups.

Towards a standardized informed consent procedure for live donor nephrectomy: What do surgeons tell their donors?

PubMed

Kortram, Kirsten; Ijzermans, Jan N M; Dor, Frank J M F

2016-08-01

Living kidney donors comprise a unique group of "patients", undergoing an operation for the benefit of others. The informed consent process is therefore valued differently. Although this is a team effort, the surgeon is responsible for performing the donor nephrectomy, and often the one held accountable, should adverse events occur. Although there is some consensus on how the informed consent procedure should be arranged, practices vary. The aim of this study was to evaluate the surgical informed consent procedure for live donor nephrectomy, with special regards to disclosure of complications. A web-based survey was sent to all kidney transplant surgeons (n = 50) in eight transplant centers with questions regarding the local procedure and disclosure of specific details. Response rate was 98% (n = 49), of which 32 (65%) were involved in living donor education; overall, transplant- (50%), vascular- (31%), and abdominal surgeons (13%), and urologists (6%) performed donor nephrectomies in the eight centers. Informed consent procedures varied, ranging from assumed to signed consent. Bleeding was the only complication every surgeon mentioned. Risk of death was always mentioned by 16 surgeons (50%), sometimes by 13 (41%), three surgeons (9%) never disclosed this disastrous complication. Reported mortality rates ranged from 0.003% to 0.1%. Mentioning frequencies for all other complications varied. Important complications are not always disclosed during the surgical informed consent process for live donor nephrectomy. Informed consent procedures vary. To optimally prepare living kidney donors for the procedure, a standardized informed consent procedure for live donor nephrectomy is highly recommended. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Renal histopathology features according to various warm ischemia times in porcine laparoscopic and open surgery model

PubMed Central

Sabbagh, Robert; Chawla, Arun; Tisdale, Britton; Kwan, Kevin; Chatterjee, Suman; Kwiecien, Jacek M.; Kapoor, Anil

2011-01-01

Background Thirty minutes has been considered as the threshold for tolerable warm ischemic time (WIT). Recent reports demonstrate recovery of renal function after longer WIT. We assessed renal histology according to different WIT in a 2-kidney porcine model. Methods Twelve female pigs were randomized to an open or laparoscopic group. Each pig was further randomized within each group to clamping the left renal artery for 5, 15, 30, 45, 60 or 180 minutes. Preclamping left renal biopsies were performed on each pig. The contralateral kidney in each animal was used as an individual control. On postoperative day 14, all animals underwent bilateral nephrectomies. Preclamping left renal biopsies and all renal specimens were evaluated by a blinded veterinary pathologist. Results One pig died in the open group after 180 minutes of clamping. Histopathology did not show any significant changes between the two groups and across clamp times from 5 to 60 minutes. After 180 minutes of laparoscopic clamping, there was evidence of diffuse necrosis. Interpretation Sixty minutes of ischemia did not show any permanent renal damage in both groups. Further studies are needed to verify these findings in humans. A prolonged ischemic time without permanent renal damage would be helpful in partial nephrectomy. Warm ischemic time of 180 minutes exceeded the renal ischemic burden based on histological features. PMID:21470513

Robotics applied in laparoscopic kidney surgery: the Yonsei University experience of 127 cases.

PubMed

Lorenzo, Enrique Ian S; Jeong, Wooju; Oh, Cheol Kyu; Chung, Byung Ha; Choi, Young Deuk; Rha, Koon Ho

2011-01-01

We report our experience on 127 kidney surgeries with the da Vinci surgical system and show the feasibility of a robotics application in a variety of kidney surgeries by both a laparoscopically-trained and a laparoscopically-naïve surgeon. Clinical data of patients who underwent kidney surgery with the da Vinci surgical system from September 2006 to April 2009 were reviewed. Data acquired from medical records included patient demographics, operative time, estimated blood loss (EBL), incidence of intraoperative complication, duration of hospital stay, blood transfusion rate, oncological outcomes, and follow-up results. One-hundred twenty-seven kidney surgeries have been conducted with the da Vinci surgical system at our institution. Three urologists--1 with formal endourology training, 1 with laparoscopic experience, and 1 laparoscopically naïve--have used it for a variety of procedures involving the kidney. The cases include 65 partial nephrectomies (RPN), 38 radical nephrectomies (RRN), and 24 nephroureterectomies with bladder cuff (RNU). Results on operative time, EBL, incidence of intraoperative injury, duration of hospital stay, and blood transfusion rate are comparable with contemporary studies. Robotics application in kidney surgery is a viable option for various procedures. Our experience shows it can be safely and effectively conducted by both laparoscopically-trained and laparoscopically-naïve surgeons once they are accustomed to the robotics system. Copyright © 2011 Elsevier Inc. All rights reserved.

Osteopontin expression and clinicopathologic correlation of oral hyperplastic reactive lesions: An institutional 6-year retrospective study

PubMed Central

Narwal, Anjali; Bala, Shashi

2017-01-01

Background and Objective: Reactive proliferations of oral cavity comprise pyogenic granuloma (PG), fibrous hyperplasia (FH), peripheral ossifying fibroma (POF), and peripheral giant-cell granuloma (PGCG). They often pose diagnostic challenges due to their overlapping clinical and histopathological features. This study was conducted to determine the frequency and clinicopathological correlation of reactive hyperplastic lesions in the oral cavity reported in our institute and compared it with other previous studies. Further evaluation of osteopontin (OPN) expression in normal gingival tissue and different types of focal reactive lesions was also done. Materials and Methods: Data of all reactive hyperplasias were retrieved, reviewed, and analyzed for age, gender, clinical presentation, and site of location. Presence and distribution of OPN were assessed using immunohistochemistry in these reactive lesions. Results: Two hundred and forty-eight reactive lesions were comprised of FH (38%), PG (23%), POF (13%), and PGCG (7%). FH was more common in males (55%) whereas other reactive lesions were more in females (68%–73%). The most frequently involved site was gingiva (59%), and most common clinical presentation was sessile growth on gingiva. OPN expression was minimal in normal gingiva. Few cases of FH, PG, and all cases of POF showed positivity for OPN in inflammatory cells, stromal cells, extracellular matrix, and in calcifications. Conclusion: Reactive hyperplastic lesions of oral cavity are mucosal responses to chronic low-grade irritation caused by plaque, calculus, and any other irritant. It is helpful to know their frequency and presentation as their early identification enables accurate patient evaluation and management. PMID:29391712

Spheroid-forming subpopulation of breast cancer cells demonstrates vasculogenic mimicry via hsa-miR-299–5p regulated de novo expression of osteopontin

PubMed Central

Shevde, Lalita A; Metge, Brandon J; Mitra, Aparna; Xi, Yaguang; Ju, Jingfang; King, Judy A; Samant, Rajeev S

2010-01-01

Abstract The growth of cancer cells as multicellular spheroids has frequently been reported to mimic the in vivo tumour architecture and physiology and has been utilized to study antitumour drugs. In order to determine the distinctive characteristics of the spheroid-derived cells compared to the corresponding monolayer-derived cells, we enriched multicellular spheroid-forming subpopulations of cells from three human breast cancer cell lines (MCF7, MCF10AT and MCF10DCIS.com). These spheroid-derived cells were injected into female athymic nude mice to assess their tumorigenic potential and were profiled for their characteristic miRNA signature. We discovered that the spheroid-derived cells expressed increased levels of osteopontin (OPN), an oncogenic protein that has been clinically correlated with increased tumour burden and adverse prognosis in patients with breast cancer metastasis. Our studies further show that increased OPN levels are brought about in part, by decreased levels of hsa-mir-299–5p in the spheroid-forming population from all three cell lines. Moreover, the spheroid-forming cells can organize into vascular structures in response to nutritional limitation; these structures recapitulate a vascular phenotype by the expression of endothelial markers CD31, Angiopoeitin-1 and Endoglin. In this study, we have validated that hsa-mir-299–5p targets OPN; de novo expression of OPN in turn plays a critical role in enhancing proliferation, tumorigenicity and the ability to display vasculogenic mimicry of the spheroid-forming cells. PMID:19538464

The utility of a "trauma 1 OP" activation at a level 1 pediatric trauma center.

PubMed

Hunt, Madison M; Stevens, Austin M; Hansen, Kristine W; Fenton, Stephen J

2017-02-01

To expedite flow of injured children suspected to require operative intervention, a "trauma 1 OP" (T1OP) activation classification was created. The purpose of this study was to review this strategy at a level 1 pediatric trauma center. A retrospective review of T1OP activations between 2003 and 2015 was performed. Children suspected of requiring neurosurgical intervention were classified as trauma 1 OP neuro (T1OP(N)). Comparisons were made to trauma 1 (T1) patients who required emergent operative intervention, excluding orthopedic injuries. Overall, 461 T1OP activations occurred (72% T1OP(N)) compared to 129 T1 activations requiring emergent surgery. Demographics were not significantly different between groups, although T1OP patients were slightly younger and more often experienced falls or were victims of abuse. Compared to T1 activations, T1OP activations had a significantly higher mortality rate (21% vs. 7%, p<0.001). Repeat head imaging was more common in the T1OP(N) group compared to imaged children in the T1 group (20% vs. 37%, p=0.05). T1OP(N) patients more often went directly to the OR (45% vs. 33%, p=0.02) and did so in a significantly faster period of time (32min vs. 53min, p<0.001). Use of the T1OP activations appropriately triaged surgical patients, resulting in significantly faster transport times to the OR. II, prognosis study. Copyright © 2017 Elsevier Inc. All rights reserved.

Anatomical Evidence that the Superior Colliculus Controls Saccades through Central Mesencephalic Reticular Formation Gating of Omnipause Neuron Activity

PubMed Central

Wang, Niping; Perkins, Eddie; Zhou, Lan; Warren, Susan

2013-01-01

Omnipause neurons (OPNs) within the nucleus raphe interpositus (RIP) help gate the transition between fixation and saccadic eye movements by monosynaptically suppressing activity in premotor burst neurons during fixation, and releasing them during saccades. Premotor neuron activity is initiated by excitatory input from the superior colliculus (SC), but how the tectum's saccade-related activity turns off OPNs is not known. Since the central mesencephalic reticular formation (cMRF) is a major SC target, we explored whether this nucleus has the appropriate connections to support tectal gating of OPN activity. In dual-tracer experiments undertaken in macaque monkeys (Macaca fascicularis), cMRF neurons labeled retrogradely from injections into RIP had numerous anterogradely labeled terminals closely associated with them following SC injections. This suggested the presence of an SC–cMRF–RIP pathway. Furthermore, anterograde tracers injected into the cMRF of other macaques labeled axonal terminals in RIP, confirming this cMRF projection. To determine whether the cMRF projections gate OPN activity, postembedding electron microscopic immunochemistry was performed on anterogradely labeled cMRF terminals with antibody to GABA or glycine. Of the terminals analyzed, 51.4% were GABA positive, 35.5% were GABA negative, and most contacted glycinergic cells. In summary, a trans-cMRF pathway connecting the SC to the RIP is present. This pathway contains inhibitory elements that could help gate omnipause activity and allow other tectal drives to induce the bursts of firing in premotor neurons that are necessary for saccades. The non-GABAergic cMRF terminals may derive from fixation units in the cMRF. PMID:24107960

Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region.

PubMed

Möbius, Patrick; Preidl, Raimund H M; Weber, Manuel; Amann, Kerstin; Neukam, Friedrich W; Wehrhan, Falk

2017-11-01

Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y‑box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region. DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively. DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels. Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

Anatomical evidence that the superior colliculus controls saccades through central mesencephalic reticular formation gating of omnipause neuron activity.

PubMed

Wang, Niping; Perkins, Eddie; Zhou, Lan; Warren, Susan; May, Paul J

2013-10-09

Omnipause neurons (OPNs) within the nucleus raphe interpositus (RIP) help gate the transition between fixation and saccadic eye movements by monosynaptically suppressing activity in premotor burst neurons during fixation, and releasing them during saccades. Premotor neuron activity is initiated by excitatory input from the superior colliculus (SC), but how the tectum's saccade-related activity turns off OPNs is not known. Since the central mesencephalic reticular formation (cMRF) is a major SC target, we explored whether this nucleus has the appropriate connections to support tectal gating of OPN activity. In dual-tracer experiments undertaken in macaque monkeys (Macaca fascicularis), cMRF neurons labeled retrogradely from injections into RIP had numerous anterogradely labeled terminals closely associated with them following SC injections. This suggested the presence of an SC-cMRF-RIP pathway. Furthermore, anterograde tracers injected into the cMRF of other macaques labeled axonal terminals in RIP, confirming this cMRF projection. To determine whether the cMRF projections gate OPN activity, postembedding electron microscopic immunochemistry was performed on anterogradely labeled cMRF terminals with antibody to GABA or glycine. Of the terminals analyzed, 51.4% were GABA positive, 35.5% were GABA negative, and most contacted glycinergic cells. In summary, a trans-cMRF pathway connecting the SC to the RIP is present. This pathway contains inhibitory elements that could help gate omnipause activity and allow other tectal drives to induce the bursts of firing in premotor neurons that are necessary for saccades. The non-GABAergic cMRF terminals may derive from fixation units in the cMRF.

Cecal Volvulus Following Laparoscopic Nephrectomy and Renal Transplantation

PubMed Central

Ravindra, Kadiyala

2009-01-01

Cecal volvulus is a rare cause of bowel obstruction that carries a high mortality. Recent surgery is known to be a risk factor for the development of cecal volvulus. We present a case of cecal volvulus following laparoscopic nephrectomy and renal transplantation. PMID:20202405

Introduction of hand-assisted retroperitoneoscopic living donor nephrectomy at Karolinska University Hospital Huddinge.

PubMed

Gjertsen, H; Sandberg, A-K A; Wadström, J; Tydén, G; Ericzon, B-G

2006-10-01

Living donor kidney transplantation accounts for about 50% of the total number of renal transplantations at our center. From 1999 through 2005, 75 out of 220 living donor nephrectomies were performed with a laparoscopic technique (LLDN). In June 2005, we introduced the technique of hand-assisted retroperitoneoscopic nephrectomy (HARS) for living donors. Since the introduction until the end of 2005, 11 out of 18 living donor nephrectomies (LDN) were performed with HARS. Reduced operation time was observed for the HARS group (mean, 166 minutes) compared with the LLDN (mean, 244 minutes). Two grafts showed delayed function, one in the LLND group and one in the HARS group. No major perioperative or postoperative complications were observed in the HARS group, whereas one patient who underwent LLDN developed severe pancreatitis. So far in our hands HARS is a fast and safe procedure with results comparable with open LDN. Compared to LLDN, we experienced reduced operation time together with the advantage of retroperitoneal access.

Cytoreductive nephrectomy vs medical therapy as initial treatment: a rational approach to the sequence question in metastatic renal cell carcinoma.

PubMed

Spiess, Philippe E; Fishman, Mayer N

2010-10-01

Renal cell carcinoma (RCC) can be considered as two distinct entities: localized and metastatic disease. We conducted a review of the scientific literature published within the past decade pertaining to cytoreductive nephrectomy for metastatic RCC. Retrospective data and historical prospective series have demonstrated the survival benefit of debulking nephrectomy in well-selected RCC patients. New medical therapies, including vascular endothelial growth factor and mTOR pathway blocking drugs, are active biological agents, with survival improvement and potential regression of metastatic and primary tumors. Our current therapeutic challenge is the optimal integration of multimodal therapy consisting of systemic therapy and surgery including cytoreductive nephrectomy, debulking, and metastasectomy. Empiric data to guide this decision are limited. The decision concerning whether medical or surgical therapy should be the primary treatment approach selected must be made on an individual basis, taking into account patient performance status, clinical parameters, and physician expertise and recommendations, thus making each case a unique therapeutic challenge.

Laparoscopic radical nephrectomy for a right renal tumor with renal vein tumor thrombus in a patient with situs inversus totalis.

PubMed

Ito, Jun; Kaiho, Yasuhiro; Iwamura, Hiromichi; Anan, Go; Sato, Makoto

2018-05-23

Situs inversus totalis (SIT) is a rare congenital anomaly characterized by complete inversion of the thoracic and abdominal organs. Many intra-abdominal and vessel anomalies have been reported in association with SIT. However, there have been no reports on the use of laparoscopic radical nephrectomy with thrombectomy for renal vein thrombus, which is considered as a safe and feasible procedure, in patients with SIT. We herein present the case of an 80-year-old man with SIT who was preoperatively diagnosed with a right renal tumor and renal vein tumor thrombus. The patient underwent laparoscopic right nephrectomy and tumor thrombectomy with no intraoperative complications. To ensure a safe procedure, the anatomy and vessels were carefully evaluated preoperatively using 3-D multiplanar reconstructed CT imaging. Assessing anatomical structures leads to safer laparoscopic radical nephrectomy for renal cell carcinoma with venous tumor thrombus in patients with SIT. © 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

Ginger Essence Effect on Nausea and Vomiting After Open and Laparoscopic Nephrectomies

PubMed Central

Hosseini, Fatemeh Sadat; Adib-Hajbaghery, Mohsen

2015-01-01

Background: Some studies reported that ginger was effective in prevention or treatment of post-surgical nausea and vomiting; however, there are controversies. In addition, no study compared the effects of ginger on nausea and vomiting after open and laparoscopic nephrectomies. Objectives: The current study aimed to compare the effect of ginger essence on nausea and vomiting after open versus laparoscopic nephrectomies. Patients and Methods: A randomized, placebo trial was conducted on two groups of patients, 50 open and 50 laparoscopic nephrectomy. Half of the subjects in each group received ginger essence and the other half received placebo. Using a visual analogue scale the severity of nausea was assessed every 15 minutes for the first two post-operative hours and the sixth hour. Frequency of vomiting was counted until the sixth hour. The placebo subgroups were treated similarly. Descriptive statistics were employed. Chi-square and Fisher’s exact tests, paired and independent samples t-test and repeated measure analysis of variance were used to analyze the data. Results: Repeated measure analysis of variance showed that the type of surgery and the type of intervention as factors had significant effects on the nausea severity scores in the nine successive measurements (P < 0.001). In the first two post-operative hours, the mean vomiting episodes was 2.92 ± 0.70 in the subjects who underwent open surgery and received placebo while it was 0.16 ± 0.37 in patients with the same surgery but receiving ginger essence (P = 0.001). The mean vomiting episodes was 6.0 ± 1.33 in the subjects who underwent laparoscopic surgery and received placebo while it was 1.39 ± 0.78 in patients with the same surgery but receiving ginger essence (P = 0.001). Conclusions: Using ginger essence was effective in reducing nausea and vomiting not only in the subjects who underwent open nephrectomy but also in the subjects of laparoscopic nephrectomy. Using ginger essence is suggested as a complementary remedy to prevent and treat post-operative nausea and vomiting in patients with nephrectomy. PMID:26339671

A case study of metastatic Xp11.2 translocation renal cell carcinoma effectively treated with sunitinib.

PubMed

Numakura, Kazuyuki; Tsuchiya, Norihiko; Yuasa, Takeshi; Saito, Mitsuru; Obara, Takashi; Tsuruta, Hiroshi; Narita, Shintaro; Horikawa, Yohei; Satoh, Shigeru; Habuchi, Tomonori

2011-10-01

We report a case of Xp11.2 translocation renal cell carcinoma (RCC) whose lung metastases were effectively treated with sunitinib. A 43-year-old woman presenting with upper abdominal pain was diagnosed with a left renal tumor. Laparoscopic left radical nephrectomy was performed. Histopathological examination of the surgical specimen revealed a clear-cell carcinoma of the left kidney. Two years later, multiple lung metastases were detected and the patient was treated daily with 50 mg sunitinib. A computed tomography scan performed after 2 cycles of sunitinib treatment revealed partial regression of these metastases. The partial regression has been maintained for >3 years. In retrospective evaluation of the primary RCC, tumor cells showed strong nuclear staining for transcription factor E3 (TFE3) protein and TFE3 split-fluorescence in-situ hybridization revealed translocation involving the TFE3 gene. These findings strongly support diagnosis of Xp11.2 translocation RCC.

Laparoscopic nephrectomy in a patient with severe scoliosis: A case report.

PubMed

Tamura, Daichi; Ito, Ayato; Kikuchi, Daichi; Tsuyukubo, Takashi; Kato, Renpei; Kato, Yoichiro; Konari, Susumu; Omori, So; Obara, Wataru

2018-05-10

Although the role of laparoscopic nephrectomy (LN) has been established, few studies have reported cases of LN in individuals with scoliosis. Here we report a case of right LN in a patient with severe right convex scoliosis. A 26-year-old man presented with a fever. His medical history comprised severe right convex lumbar scoliosis. CT revealed right hydronephrosis and right kidney stones. Pyelonephritis requiring nephrectomy was diagnosed. Right LN was feasible with elaborate perioperative care. The postoperative course was uneventful with no relapse of urinary tract infection. © 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

CD44v6 Regulates Growth of Brain Tumor Stem Cells Partially through the AKT-Mediated Pathway

PubMed Central

Jijiwa, Mayumi; Demir, Habibe; Gupta, Snehalata; Leung, Crystal; Joshi, Kaushal; Orozco, Nicholas; Huang, Tiffany; Yildiz, Vedat O.; Shibahara, Ichiyo; de Jesus, Jason A.; Yong, William H.; Mischel, Paul S.; Fernandez, Soledad; Kornblum, Harley I.; Nakano, Ichiro

2011-01-01

Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC) has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6) in BTSC of a subset of glioblastoma multiforme (GBM). Patients with CD44high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44high GBM but not from CD44low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN), increased expression of phosphorylated AKT in CD44high GBM, but not in CD44low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKTpathway. PMID:21915300

Effect of sustained gene delivery of platelet-derived growth factor or its antagonist (PDGF-1308) on tissue-engineered cementum.

PubMed

Anusaksathien, Orasa; Jin, Qiming; Zhao, Ming; Somerman, Martha J; Giannobile, William V

2004-03-01

Cementum, a mineralized tissue lining the tooth root surface, is destroyed during the inflammatory process of periodontitis. Restoration of functional cementum is considered a criterion for successful regeneration of periodontal tissues, including formation of periodontal ligament, cementum, and alveolar bone. Short-term administration of platelet-derived growth factor (PDGF) has been shown to partially regenerate periodontal structures. Nonetheless, the role of PDGF in cementogenesis is not well understood. The aim of the present study was to determine the effect of sustained PDGF gene transfer on cementum formation in an ex vivo ectopic biomineralization model. Osteocalcin (OC) promoter-driven SV40 transgenic mice were used to obtain immortalized cementoblasts (OCCM). The OCCM cells were transduced with adenoviruses (Ad) encoding either PDGF-A, an antagonist of PDGF signaling (PDGF-1308), a control virus (green fluorescent protein, GFP), or no treatment (NT). The transduced cells were incorporated into polymer scaffolds and implanted subcutaneously into severe combined immunodeficient (SCID) mice. The implants were harvested at 3 and 6 weeks for histomorphometric analysis of the newly formed mineralized tissues. Northern blot analysis was performed to determine the expression levels of mineral-associated genes including bone sialoprotein (BSP), OC, and osteopontin (OPN) in the cell-implant specimens at 3 and 6 weeks. The results indicated mineralization was significantly reduced in both the Ad/PDGF-A and Ad/PDGF-1308 treated specimens when compared to the NT or Ad/GFP groups at 3 and 6 weeks (P<0.01). In addition, the size of the implants treated with Ad/PDGF-A and Ad/PDGF-1308 was significantly reduced compared to implants from Ad/GFP and NT groups at 3 weeks (P<0.05). At 6 weeks, the size of implants and mineral formation increased in NT, Ad/GFP, and Ad/PDGF-A groups, while the Ad/PDGF-1308 treated implants continued to decrease in size and mineral formation (P<0.01). Northern blot analysis revealed that in the Ad/PDGF-A treated implants OPN was increased, whereas OC gene expression was downregulated at 3 weeks. In the Ad/PDGF-1308 treated implants, BSP, OC, and OPN were all downregulated at 3 weeks. At 3 weeks, the Ad/PDGF-A treated implants contained significantly higher multinucleated giant cell (MNGC) density compared to NT, Ad/GFP, and Ad/PDGF-1308 specimens. The MNGC density in NT, Ad/GFP, and Ad/PDGF-A treated groups reduced over time, while the Ad/PDGF-1308 transduced implants continued to exhibit significantly higher MNGC density compared with the other treatment groups at 6 weeks. The results showed that continuous exposure to PDGF-A had an inhibitory effect on cementogenesis, possibly via the upregulation of OPN and subsequent enhancement of MNGCs at 3 weeks. On the other hand, Ad/PDGF-1308 inhibited mineralization of tissue-engineered cementum possibly due to the observed downregulation of BSP and OC and a persistence of stimulation of MNGCs. These findings suggest that continuous exogenous delivery of PDGF-A may delay mineral formation induced by cementoblasts, while PDGF is clearly required for mineral neogenesis.

Retroperitoneal laparoscopic nephrectomy: the effect of the learning curve, and concentrating expertise, on operating times.

PubMed

Skinner, Adrian; Maoate, Kiki; Beasley, Spencer

2010-05-01

Laparoscopic nephrectomy is an accepted alternative to open nephrectomy. We analyzed our first 80 procedures of laparoscopic nephrectomy to evaluate the effect of experience and configuration of service on operative times. A retrospective review of 80 consecutive children who underwent retroperitoneal laparoscopic nephrectomy or heminephrectomy during an 11-year period from 1997 at Christchurch Hospital (Christchurch, New Zealand) was conducted. Operative times, in relation to the experience of the surgeon for this procedure, were analyzed. Four surgeons, assisted by an annually rotating trainee registrar, performed the procedure in 26 girls and 54 boys (range, 8 months to 15 years). Operating times ranged from 38 to 225 minutes (mean, 104). The average operative time fell from 105 to 90 minutes. One surgeon performed 40% of the procedures and assisted with a further 55%. The operative times for all surgeons showed a tendency to reduce, but this was not marked. Most procedures were performed by two surgeons working together, although one surgeon was involved in the majority of cases. The lead surgeon is often assisted by a fellow consultant colleague. Operative times were influenced by experience, but not markedly so. The shorter operative times and minimal "learning curve," compared with other reported series, may, in part, be due to the involvement of two surgeons experienced in laparoscopy for the majority of cases.

Retroperitoneoscopic versus open surgical radical nephrectomy for 152 Chinese patients with large renal cell carcinoma in clinical stage cT2 or cT3a: A long-term retrospective comparison.

PubMed

Zhu, Xuhui; Yang, Xiaoyong; Hu, Xiaopeng; Zhang, Xiaodong

2016-01-01

To evaluate the feasibility, safety, and long-term efficacy of retroperitoneal laparoscopic radical nephrectomy for Chinese patients with a mean body mass index (BMI) of ≤24 and large renal cell carcinoma (RCC). A long-term retrospective analysis of clinical data of 152 Chinese patients with a mean BMI of ≤24 and large RCC. Totally, 84 patients who underwent retroperitoneal laparoscopic radical nephrectomy (RPNx) for tumor size >7 cm (group 1) were compared with 68 patients, who underwent open radical nephrectomy (group 2) for tumor with similar size characteristics. Moreover, their 10 years outcomes (or the number of patients) were divided into segments (e.g., the first 5 and last 5 years, the first 30 and last 30 patients, etc.) looking for the differences of learning curve. RPNx patients experienced significantly shorter hospital stay, less blood loss, and had a decreased analgesic requirement and more rapid convalescence. The incidence of intra- and post-operative complications was 6% and 13%, 7.2% and 16.1% in the two groups, respectively. The 5-year survival rates of the two groups were 86% and 82%, respectively. Retroperitoneal laparoscopic radical nephrectomy for patients with a mean BMI of ≤24 and large RCC is safe, feasible, and the efficacious procedure produced good long-term results.

A Randomized, Prospective, Parallel Group Study of Laparoscopic vs. Laparoendoscopic Single Site Donor Nephrectomy for Kidney Donation

PubMed Central

Aull, Meredith J.; Afaneh, Cheguevara; Charlton, Marian; Serur, David; Douglas, Melissa; Christos, Paul J.; Kapur, Sandip; Del Pizzo, Joseph J.

2014-01-01

Few prospective, randomized studies have assessed benefits of laparoendoscopic single site donor nephrectomy (LESS-DN) over laparoscopic donor nephrectomy (LDN). Our center initiated such a trial in January 2011, following subjects randomized to LESS-DN vs. LDN from surgery through 5 years post-donation. Subjects complete recovery/satisfaction questionnaires at 2, 6, and 12 months post-donation; transplant recipient outcomes are also recorded. 100 subjects (49 LESS-DN, 51 LDN) underwent surgery; donor demographics were similar between groups, and included a predominance of female, living unrelated donors, mean age of 47 years who underwent left donor nephrectomy. Operative parameters (overall time, time to extraction, warm ischemia time, blood loss) were similar between groups. Conversion to hand-assist laparoscopy was required in 3 LESS-DN (6.1%) vs. 2 LDN (3.9%; P=0.67). Questionnaires revealed 97.2% of LESS-DN vs. 79.5% of LDN (P=0.03) were 100% recovered by two months after donation. No significant difference was seen in satisfaction scores between the groups. Recipient outcomes were similar between groups. Our randomized trial comparing LESS donor nephrectomy to LDN confirms that LESS-DN offers a safe alternative to conventional LDN in terms of intra- and post-operative complications. LDN and LESS-DN offer similar recovery and satisfaction after donation. PMID:24934732

Hand-assisted Laparoscopic Nephrectomy in Living-donor Kidneys With Multiple Arteries: Experience of a Transplant Center.

PubMed

Bandín Musa, Alfonso Ricardo; Montes de Oca, Jorge

2016-04-01

Hand-assisted laparoscopic nephrectomy is a relatively new procedure in our country. This article reports on one of the largest number of this procedure in kidneys with multiple vessels. We reviewed all cases of hand-assisted laparoscopic nephrectomy from July 2002 to February 2009. Results were then descriptive, with statistical analyses performed with SPSS software (SPSS: An IBM Company, version 10.0, IBM Corporation, Armonk, NY, USA). From July 2002 to February 2009, 165 patients had hand-assisted laparoscopic nephrectomy, with 96.9% being the left kidney. We found a prevalence of 18.7% (n = 31) of kidneys with multiple arteries, with 8 of these having multiple principal arteries, 9 with superior polar artery, and 14 with inferior polar artery. Twenty-nine donors (17.57%) presented with more than 1 principal vein. Warm ischemia was longer in kidneys with multiple arteries (4.16 vs 3.96 min); recipient renal function (evaluated by creatinine levels at day 5 after transplant) was 1.63 mg/dL in kidneys with single artery versus 1.27 mg/dL in kidneys with multiple arteries. There were no significant differences for time of surgery, bleeding, and discharge of the donor. We found no differences in kidney function between single and multiple artery kidneys, resulting in the conclusion that hand-assisted laparoscopic nephrectomy offers an effective option for kidney donors, including those with multiple arteries.

[Robotic assisted laparoscopic living donor nephrectomy: preoperative assessment and results of 100 cases].

PubMed

Laplace, B; Ladrière, M; Claudon, M; Eschwege, P; Kessler, M; Hubert, J

2014-04-01

To assess short term morbidity and renal function after robotic laparoscopic living donor nephrectomy. We performed a retrospective analysis of 100 consecutives patients undergoing a robotic laparoscopic living donors nephrectomy. We analyzed isotopic measure of the renal function before and 4 months after surgery, the side, the number of arteries, the blood loss, the operative time and warm ischemia time. In the outcomes, we collected the complications, the length of stay, and for the receiver, the renal function recovery time, dialysis, survival and renal function at one year. Left kidney nephrectomy was performed in 85 patients and we observed 25 multiples renal arteries. Mean estimated blood loss was 0,8 g/dL. Mean operative time and warm ischemia time were respectively 174 ± 30 and 4.8 ± 1.7 minutes. Seven complications occured, with 2 major (Clavien-Dindo System). Mean length of stay was 5.1 ± 1.9 days. Mean glomerular filtration decrease was 26% and remains stable at one year after surgery. Grafts had an immediate renal function recovery for 99%, and were all functional after one year, with mean MDRD clearance of 57 ± 14mL/min. Robotic procedure in laparoscopic living donor nephrectomy seems to guarantee low morbidity and the stability of the renal function decrease of 26%. Copyright © 2013. Published by Elsevier Masson SAS.

[Living kidney donation].

PubMed

Timsit, M-O; Kleinclauss, F; Mamzer Bruneel, M F; Thuret, R

2016-11-01

To review ethical, legal and technical aspects of living kidney donor surgery. An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords: Donor nephrectomy; Kidney paired donation; Kidney transplantation; Laparoscopic nephrectomy; Living donor; Organs trafficking; Robotic assisted nephrectomy; Vaginal extraction. French legal documents have been reviewed using the government portal (http://www.legifrance.gouv.fr). Articles were selected according to methods, language of publication and relevance. A total of 6421 articles were identified; after careful selection, 161 publications were considered of interest and were eligible for our review. The ethical debate focuses on organ shortage, financial incentive, organ trafficking and the recent data suggesting a small but significant increase risk for late renal disease in donor population. Legal decisions aim to increase the number of kidneys available for donation, such as kidney-paired donation that faces several obstacles in France. Laparoscopic approach became widely used, while robotic-assisted donor nephrectomy failed to demonstrate improved outcome as compared with other minimal invasive techniques. Minimally invasive living donor nephrectomy aims to limit side effects in the donor without increasing the morbidity in this specific population of healthy persons; long term surveillance to prevent the onset of renal disease in mandatory. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Postoperative elevation in creatine kinase and its impact on renal function in patients undergoing complex partial nephrectomy.

PubMed

Sidana, Abhinav; Walton-Diaz, Annerleim; Truong, Hong; Siddiqui, M Minhaj; Miao, Ning; Shih, Johanna; Mannes, Andrew; Bratslavsky, Gennady; Linehan, W Marston; Metwalli, Adam R

2016-07-01

To identify the risk factors associated with development of postoperative elevation of creatine kinase (CK) and study its effect on renal function in patients who underwent complex multifocal partial nephrectomy (PN). Patients who underwent PN at National Cancer Institute between January 2007 and December 2012 were included in the study. Elevated serum CK was defined as >2000 U/L. Kidney function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR). Changes were reported as percent change from preoperative values and compared using the Wilcoxon test. Regression analysis was performed to identify the predictors of elevation in CK and decline in eGFR. From 407 total cases, 207 had adequate CK data for analysis. Median number of tumors removed was 3 (1-70). Median peak CK was 1458 (82-36,788). Forty-two percent developed CK elevation >2000 U/L. Factors associated with postoperative elevation of CK > 2000 were young age (p = 0.009), high BMI (p = 0.003) and operating room time (p < 0.001). Although CK > 2000 was associated with significantly greater decline in eGFR (37.4 vs. 20.3 %, p < 0.001) in immediate postoperative period, this change largely resolved to a much less clinically relevant (9.2 vs 3.3 %, p = 0.040) change after 3 months. On multivariate analysis, postoperative elevation in CK was not found to be an independent factor determining renal function at 3 months. In our cohort, a significant proportion of patients developed CK elevations >2000 U/L. While patients with elevated CK had more decline in eGFR in immediate postoperative period, postoperative elevations of CK did not appear to impact overall long-term renal function in patients undergoing PN.

Retroperitoneal versus transperitoneal robotic-assisted laparoscopic partial nephrectomy: a matched-pair, bicenter analysis with cost comparison using time-driven activity-based costing.

PubMed

Laviana, Aaron A; Tan, Hung-Jui; Hu, Jim C; Weizer, Alon Z; Chang, Sam S; Barocas, Daniel A

2018-03-01

To perform a bicenter, retrospective study of perioperative outcomes of retroperitoneal versus transperitoneal robotic-assisted laparoscopic partial nephrectomy (RALPN) and assess costs using time-driven activity-based costing (TDABC). We identified 355 consecutive patients who underwent RALPN at University of California Los Angeles and the University of Michigan during 2009-2016. We matched according to RENAL nephrometry score, date, and institution for 78 retroperitoneal versus 78 transperitoneal RALPN. Unadjusted analyses were performed using McNemar's Chi-squared or paired t test, and adjusted analyses were performed using multivariable repeated measures regression analysis. From multivariable models, predicted probabilities were derived according to approach. Cost analysis was performed using TDABC. Patients treated with retroperitoneal versus transperitoneal RALPN were similar in age (P = 0.490), sex (P = 0.715), BMI (P = 0.273), and comorbidity (P = 0.393). Most tumors were posterior or lateral in both the retroperitoneal (92.3%) and transperitoneal (85.9%) groups. Retroperitoneal RALPN was associated with shorter operative times (167.0 versus 191.1 min, P = 0.001) and length of stay (LOS) (1.8 versus 2.7 days, P < 0.001). There were no differences in renal function preservation or cancer control. In adjusted analyses, retroperitoneal RALPN was 17.6-min shorter (P < 0.001) and had a 76% lower probability of LOS at least 2 days (P < 0.001). Utilizing TDABC, transperitoneal RALPN added $2337 in cost when factoring in disposable equipment, operative time, LOS, and personnel. In two high-volume, tertiary centers, retroperitoneal RALPN is associated with reduced operative times and shortened LOS in posterior and lateral tumors, whereas sharing similar clinicopathologic outcomes, which may translate into lower healthcare costs. Further investigation into anterior tumors is needed.

Robot-assisted partial nephrectomy for hilar tumors: perioperative outcomes.

PubMed

Eyraud, Rémi; Long, Jean-Alexandre; Snow-Lisy, Devon; Autorino, Riccardo; Hillyer, Shahab; Klink, Joseph; Rizkala, Emad; Stein, Robert J; Kaouk, Jihad H; Haber, Georges-Pascal

2013-06-01

To compare perioperative outcomes of robot-assisted partial nephrectomy (RAPN) for hilar vs nonhilar tumors. The study retrospectively reviewed 364 patients with available computed tomography scans undergoing RAPN. Demographic data and perioperative outcomes results were compared between the hilar (group 1, n = 70) and nonhilar tumors (group 2, n = 294). Multivariate analysis was used to identify predictors of warm ischemia time (WIT), estimated blood loss (EBL), major perioperative complications, and postoperative renal function. There were no differences with respect to demographic variables. Hilar tumors had higher RENAL (radius, exophytic/endophytic properties of the tumor, nearness of tumor deepest portion to the collecting system or sinus, anterior/posterior descriptor and the location relative to polar lines) scores (P <.001) and were larger (3.9 vs 2.6 cm, P <.001). Surgeries for hilar tumors were associated with greater operative time (210 vs 180 minutes, P <.001), longer WIT (27 vs 17 minutes, P <.001), and increased EBL (250 vs 200 mL, P = .04). No differences were noted in transfusion rate, length of stay, complications (overall and major) and positive margins. Postoperative estimated glomerular filtration rate showed no significant difference between hilar vs nonhilar patients on postoperative day 3 (70.12 vs 74.71 mL/min/1.73 m(2), P = .31) or at last follow-up (72.62 vs 75.78 mL/min/1.73 m(2), P = .40), respectively. Multivariate analysis found hilar location was independently associated with increased WIT without significant changes in EBL, major complications, or postoperative renal function. RAPN represents a safe and effective procedure for hilar tumors. Hilar location for patients undergoing RAPN in a high-volume institution seems not be associated with an increased risk of transfusions, major complications, or decline of early postoperative renal function. Copyright © 2013 Elsevier Inc. All rights reserved.

Laparoscopic partial nephrectomy: A series of one hundred cases performed by the same surgeon.

PubMed

Campero, José M; Ramos, Christián G; Valdevenito, Raúl; Mercado, Alejandro; Fullá, Juan

2012-09-01

Laparoscopic partial nephrectomy (LPN) has become the first-line surgical technique for the management of renal tumors smaller than 4 cm. Its main advantages are an excellent oncologic control together with the preservation of nephron units. Moreover, it implies a shorter length of hospital stay, less postoperative pain, and shorter recovering times for patients. We included 100 patients who consecutively underwent LPN between years 2000 and 2010 in our institution. The aim was to present our experience and to compare it with the results reported in the literature by other centers. This was a prospective study. One hundred consecutive patients (67 men and 33 women) who underwent LPN within years 2000 and 2010 were included in the study. In all cases, surgery was performed by the same surgeon (JMC). Data were collected retrospectively, including clinical and histopathologic information, as well as surgical and functional results. Statistical analysis was performed using the chi-square test and SPSS v17 software. A P-value < 0.05 was considered significant in all the analyses. The indication for LPN was a renal tumor or a complex renal cyst in the 96% of the cases. A retroperitoneal or transperitoneal approach was performed in the 62% and 38% of the cases, respectively. The average size of the tumor was 3.3 cm (range 1-8). The mean surgical time was 103.5 min (range 40-204). The mean estimated blood loss was 193.7 cc. The average hospital length of stay was 50.2 h. Six (6%) patients had complications related to the surgery. The majority (n = 2) was due to intraoperative bleeding. With an average follow-up time of 42.1 months, there is no tumor recurrence reported up to now. Our results are similar to those reported in the international literature. LPN is a challenging surgical technique that in hands of a trained and experienced surgeon has excellent and reproducible results for the management of small renal masses and cysts.

Single surgeon's experience with laparoscopic versus robotic partial nephrectomy: perioperative outcomes/complications and influence of tumor characteristics on choice of therapy.

PubMed

Lee, Nora G; Zampini, Anna; Tuerk, Ingolf

2012-10-01

Laparoscopic (LPN) and robotic partial nephrectomy (RPN) may offer similar advantages for nephron-sparing surgery (NSS). We evaluated the perioperative outcomes and complications of LPN versus RPN and sought to evaluate if one technique may have more favorable outcomes over another based on tumor characteristics. All patients who underwent LPN and RPN by a single surgeon were retrospectively reviewed. The surgeon almost exclusively performed LPN from February 2009 to January 2011 and RPN from January 2011 to January 2012. Patient demographics, tumor characteristics, perioperative outcomes, short term renal functional data, and complications were reviewed. Operative time (OT), warm ischemia time (WIT), and estimated blood loss (EBL) were evaluated for each technique when tumor characteristics were divided by size, location, distance to collecting system, and overall tumor complexity based on nephrometry scoring. Of 39 laparoscopic cases and 30 robotic cases, there were no significant differences in perioperative outcomes, short term renal functional data, or complications between the two groups except for WIT which was shorter in the LPN group (p = 0.006). For medium complexity tumors, OT was less for LPN compared to RPN (p = 0.04); for high complexity tumors, EBL was reduced for RPN compared to LPN cases (p = 0.003). When tumor characteristics were individualized, LPN may be superior to RPN for WIT for small, anterior and exophytic tumors, and tumors located > 5 mm from the collecting system. LPN and RPN appear more equivocal for WIT in posteriorly located tumors. Reduced EBL may be a benefit with RPN for larger tumors. Although WIT was less in patients undergoing LPN compared to RPN, perioperative outcomes and complications remain similar. RPN may be beneficial for approaching more difficult, posterior tumors, whereas LPN may be a better technique for WIT for simple, accessible renal tumors. Reduced EBL may be a benefit for RPN for highly complex tumors.

Renal mass anatomic characteristics and perioperative outcomes of laparoscopic partial nephrectomy: a critical analysis.

PubMed

Tsivian, Matvey; Ulusoy, Said; Abern, Michael; Wandel, Ayelet; Sidi, A Ami; Tsivian, Alexander

2012-10-01

Anatomic parameters determining renal mass complexity have been used in a number of proposed scoring systems despite lack of a critical analysis of their independent contributions. We sought to assess the independent contribution of anatomic parameters on perioperative outcomes of laparoscopic partial nephrectomy (LPN). Preoperative imaging studies were reviewed for 147 consecutive patients undergoing LPN for a single renal mass. Renal mass anatomy was recorded: Size, growth pattern (endo-/meso-/exophytic), centrality (central/hilar/peripheral), anterior/posterior, lateral/medial, polar location. Multivariable models were used to determine associations of anatomic parameters with warm ischemia time (WIT), operative time (OT), estimated blood loss (EBL), intra- and postoperative complications, as well as renal function. All models were adjusted for the learning curve and relevant confounders. Median (range) tumor size was 3.3 cm (1.5-11 cm); 52% were central and 14% hilar. While 44% were exophytic, 23% and 33% were mesophytic and endophytic, respectively. Anatomic parameters did not uniformly predict perioperative outcomes. WIT was associated with tumor size (P=0.068), centrality (central, P=0.016; hilar, P=0.073), and endophytic growth pattern (P=0.017). OT was only associated with tumor size (P<0.001). No anatomic parameter predicted EBL. Tumor centrality increased the odds of overall and intraoperative complications, without reaching statistical significance. Postoperative renal function was not associated with any of the anatomic parameters considered after adjustment for baseline function and WIT. Learning curve, considered as a confounder, was independently associated with reduced WIT and OT as well as reduced odds of intraoperative complications. This study provides a detailed analysis of the independent impact of renal mass anatomic parameters on perioperative outcomes. Our findings suggest diverse independent contributions of the anatomic parameters to the different measures of outcomes (WIT, OT, EBL, complications, and renal function) emphasizing the importance of the learning curve.

Renal pelvic anatomy is associated with incidence, grade, and need for intervention for urine leak following partial nephrectomy.

PubMed

Tomaszewski, Jeffrey J; Cung, Bic; Smaldone, Marc C; Mehrazin, Reza; Kutikov, Alexander; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2014-11-01

Although the effect of tumor complexity on perioperative outcome measures is well established, the impact of renal pelvic anatomy on perioperative outcomes remains poorly defined. To evaluate renal pelvic anatomy as an independent predictor of urine leak in moderate- and high-complexity tumors undergoing nephron-sparing surgery. Patients undergoing open partial nephrectomy (PN) for localized RCC were stratified into intermediate- and high-complexity groups using a nephrometry score (7-9 and 10-12, respectively). A renal pelvic score (RPS) was defined by the percentage of renal pelvis contained inside the volume of the renal parenchyma. On this basis, patients were categorized as having an intraparenchymal (>50%) or extraparenchymal (<50%) renal pelvis. Characteristics of patients with and without an intraparenchymal renal pelvic anatomy were compared. Inclusion criteria were met by 255 patients undergoing PN for intermediate (73.6%) and complex (26.4%) localized renal tumors (mean size: 4.6±2.9cm). Twenty-four (9.6%) renal pelves were classified as completely intraparenchymal. Following stratification by RPS, groups differed with respect to Charlson comorbidity index, body mass index, and largest tumor size, while no differences were observed between hospital length of stay, nephrometry score, estimated blood loss, operative time, and age. Intrarenal pelvic anatomy was associated with a markedly increased risk of urine leak (75% vs 6.5%; p=0.001), secondary intervention (37.5% vs 3.9%; p<0.001), and prolonged duration of urine leak (93±62 d vs 56±29 d; p=0.025). Intraparenchymal renal pelvic anatomy is an uncommon anatomic variant associated with an increased rate of urine leak following PN. Elevated pressures within a small intraparenchymal renal pelvis might explain the increased risk. Preoperative imaging characteristics suggestive of increased risk for urine leak should be considered in perioperative management algorithms. Copyright © 2013. Published by Elsevier B.V.

Anatomical study of renal arterial vasculature and its potential impact on partial nephrectomy.

PubMed

Macchi, Veronica; Crestani, Alessandro; Porzionato, Andrea; Sfriso, Maria Martina; Morra, Aldo; Rossanese, Marta; Novara, Giacomo; De Caro, Raffaele; Ficarra, Vincenzo

2017-07-01

To validate Graves' classification of the intrarenal arteries and to verify the absence of collateral arterial blood supply between different renal segments, in order to maximize peri-operative and functional outcomes of partial nephrectomy. The study was performed on 15 normal kidneys sampled from eight unembalmed cadavers. Kidneys with the surrounding perirenal fat tissue were removed en bloc with the abdominal segment of the aorta. The renal artery was injected with acrylic and radiopaque resins, with the specimen suspended in water. CT examination of the injected kidneys was performed to analyse the branches located deeply. After imaging acquisition, the specimens were treated with sodium hydroxide for removal of the parenchyma to obtain vascular casts. Ten casts (66.6%) showed the classic subdivision of the main artery into single posterior and anterior branches. With regard to the distribution of the segmental or second-order arteries, only two casts (13%) showed a pattern similar to that described by Graves, characterized by four segmental (second-order) branches coming from the anterior renal artery (apical, superior, middle and inferior). In the remaining 13 kidneys (87%) a different arterial vascular network was detected. In 10 casts (80%) a single renal segment was vascularized by two or more different branches coming from an artery leading to another segment (multiple vascularization). Multiple vascularization was observed in three (20%) apical segments, five (33%) superior segments, six (40%) middle segments, seven (47%) inferior segments and two (13%) posterior segments. This study shows that in the human kidneys the arterial vasculature is frequently different from that described by Graves. Moreover, in a significant percentage of cases, a single renal segment receives two or more branches that originate from an artery leading to another segment. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Predicted versus observed 30-day perioperative outcomes using the ACS NSQIP surgical risk calculator in patients undergoing partial nephrectomy for renal cell carcinoma.

PubMed

Blair, Brian M; Lehman, Erik B; Jafri, Syed M; Kaag, Matthew G; Raman, Jay D

2018-06-04

The purpose of the study was to evaluate the accuracy of the American College of Surgeons NSQIP Surgical Risk Calculator for predicting risk-adjusted 30-day outcomes for patients undergoing partial nephrectomy (PN) for renal cell carcinoma (RCC). A single institution, multi-surgeon, prospectively maintained database was queried for patients undergoing PN for RCC from 1998 to 2015. 21 preoperative factors were analyzed for each patient with predicted risk for 30-day complications, mortality, and length of stay (LOS) calculated. Differences between the mean predicted risk and observed rate of surgical outcomes were determined using two-sided one-sample t test with significance at p < 0.05. Subgroup analyses of outcomes stratified by surgical approach were also performed. 470 patients undergoing PN for RCC were analyzed. Comparing NSQIP predicted to observed outcomes, clinically significant underestimations occurred with rates of overall complications (9.16 vs. 16.81%, p < 0.001), surgical site infections [SSI] (1.65 vs. 2.77%, p < 0.001), urinary tract infection [UTI] (1.41 vs. 3.40%, p < 0.001), and LOS (3.25 vs. 3.73 days, p < 0.001). On subgroup analysis, 209 open PN and 261 minimally invasive PN (MIPN) were performed. The NSQIP calculator consistently underestimated overall complications, SSI, UTI, and LOS (p < 0.001) among both surgical approaches, while overestimating MIPN severe complications (p < 0.001). Clinically important differences persisted when stratifying the MIPN group by laparoscopic (N = 111) and robotic (N = 150) approaches. The ACS NSQIP Surgical Risk Calculator had significant discrepancies among observed and predicted outcomes. Additional analyses confirmed these differences remained significant irrespective of surgical approach. These findings emphasize the need for urologic oncology-specific calculators to better predict surgical outcomes in this complex patient population.

Robot-assisted partial nephrectomy in 95 consecutive patients: Oncological and functional outcomes at 3 years of follow-up.

PubMed

Castillo, O A; Rodríguez-Carlin, A; Borgna, V

2016-05-01

We present the oncological and functional results from a series of 43 patients with renal tumours, treated consecutively with robot-assisted partial nephrectomy (RPN). Between 2010 and 2014, we performed 95 RPNs. To assess the results, we included only those patients (n=43) who had a minimum follow-up of 2 years. A descriptive analysis was conducted of the demographic characteristics and perioperative variables. We employed Kaplan-Meier curves to assess overall survival, cancer-specific survival and recurrence-free survival. The patients' mean age was 53.1±13.5 years. The mean preoperative tumour size was 3.7±2.3cm. The mean surgical time was 102.2±37.1min. The mean ischemia time was 21.27±7.74minutes, with a median intraoperative bleeding volume of 150mL (IQR, 87.5-425). There was a 7% rate of postoperative complications (Clavien≥III). There was no mortality. The average Fürhman grade was 2.5±0.56. There were no positive surgical margins or local recurrences. The median follow-up was 38±8 months, with an overal survival, recurrence-free survival and cancer-specific survival of 100% at 3 years of follow-up. The recurrence-free survival was 92,3% at 48 months of follow-up. The mean preoperative glomerular filtration rate was 91.04±28.17mL/min/1.73m(2), and the postoperative rate was 89.9±27.69mL/min/1.73m(2), with a nonsignificant reduction (P=.74). The functional and oncological results of our series confirm the safety and efficacy of RPN. RPN offers optimal preservation of renal function and oncological control in the medium term. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

A Study of Relationship of Atheroembolic Risk Factors with Postoperative Recovery in Renal Function after Partial Nephrectomy in Patients Staged T1-2 Renal Cell Carcinoma during Median 4-Year Follow-up.

PubMed

Kim, Sung Han; Kang, Kyung Min; Yu, Ami; Lee, Jung Hoon; Nam, Byung Ho; Lee, Eun Sik

2016-01-01

The objective of this study is to evaluate the relationship of atheroembolic risk factors with postoperative recovery of renal function after on-clamp partial nephrectomy (PN) with warm ischemia in patients with staged T1-2 renal cell carcinoma (RCC). A total of 234 patients from 2004 to 2012 were included, and their clinicopathologic and operative parameters, including atheroembolic risk factors were reviewed retrospectively. Renal function, as determined by estimated glomerular filtration rate (eGFR) and measurement of serum creatinine level (Cr) at each scheduled follow-up for a median four years, was compared between the high-risk (HR) group (n=49, ≥ five risk factors) and the low-risk (LR) group (n=185, < five risk factors). Except for baseline renal function and number of risk factors for atheroembolism, differences in characteristics between groups were comparatively insignificant. At 3 months after the operation, Cr and eGFR differed significantly between the two groups (p < 0.05), but no differences were observed afterward. Significant deterioration from baseline in Cr and eGFR was observed in both groups at 1 month after the operation, with a greater change in the HR group (p < 0.05). From measurement to measurement, significantly faster deterioration in Cr and eGFR was observed in the HR group than in the LR group until 6 months after the operation (Cr: LR, 0.02 mg/dL and HR, 0.13 mg/dL; eGFR: LR, 1.50 mL/min/1.73 m(2) and HR, 6.38 mL/min/1.73 m(2); p < 0.05). The presence of atheroembolic risk factors may negatively influence postoperative recovery of renal function after PN in patients with localized RCC.

A Literature Review of Renal Surgical Anatomy and Surgical Strategies for Partial Nephrectomy

PubMed Central

Klatte, Tobias; Ficarra, Vincenzo; Gratzke, Christian; Kaouk, Jihad; Kutikov, Alexander; Macchi, Veronica; Mottrie, Alexandre; Porpiglia, Francesco; Porter, James; Rogers, Craig G.; Russo, Paul; Thompson, R. Houston; Uzzo, Robert G.; Wood, Christopher G.; Gill, Inderbir S.

2016-01-01

Context A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. Objective To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). Evidence acquisition A literature review was conducted. Evidence synthesis Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. Conclusions Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. Patient summary In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes. PMID:25911061

Need for intraoperative ultrasound and surgical recommendation for partial nephrectomy: correlation with tumor imaging features and urologist practice patterns.

PubMed

Sun, Maryellen R M; Wagner, Andrew A; San Francisco, Ignacio F; Brook, Alexander; Kavoussi, Louis; Russo, Paul; Steele, Graeme; Viterbo, Rosalia; Pedrosa, Ivan

2012-03-01

This study aimed to evaluate the need for intraoperative ultrasound (IOUS) and recommendation for surgical approach in the resection of renal tumors through a survey of practicing urologists, with correlation to tumor imaging features and urologist practice pattern. An institutional review board-approved retrospective review, compliant with the Health Insurance Portability and Accountability Act, of 44 renal tumors that underwent laparoscopic partial nephrectomy at the study institution was performed. The numeric component of the RENAL nephrometry score (radius [diameter], % exophytic, nearness [to collecting system/renal sinus], location) was calculated for each case using preoperative computed tomography/magnetic resonance imaging. Five anonymized images of each tumor were presented to 4 academic urologists with varying practice patterns. Reviewers independently scored each case for its need for IOUS, for recommendation of a surgical technique, and for the difficulty of the proposed surgery. The RENAL scores were as follows: RENAL 1 (low complexity, score 4-6; n = 19); RENAL 2 (moderate complexity, score 7-9; n = 23); RENAL 3 (high complexity, score 10-12; n = 2). The only RENAL score component significantly influencing need for IOUS was percentage exophytic (P = 0.00002). There was an inverse relationship between normalized and averaged need for IOUS and percentage exophytic (P < 0.0001). The predominant influence for recommendation of surgical method was the reviewer him/herself, with each reviewer's recommendations closely matching his/her practice pattern. Size and percentage exophytic represented the only tumor features significantly (P = 0.03) influencing surgical recommendation. There was a significant difference in the perceived need for IOUS and surgical recommendation when 4 academic urologists reviewed a series of renal masses requiring resection. Percentage exophytic correlated inversely with need for IOUS. Urologist's practice pattern and tumor size and percentage exophytic were most predictive of surgical recommendation.

Zonal NePhRO scoring system: a superior renal tumor complexity classification model.

PubMed

Hakky, Tariq S; Baumgarten, Adam S; Allen, Bryan; Lin, Hui-Yi; Ercole, Cesar E; Sexton, Wade J; Spiess, Philippe E

2014-02-01

Since the advent of the first standardized renal tumor complexity system, many subsequent scoring systems have been introduced, many of which are complicated and can make it difficult to accurately measure data end points. In light of these limitations, we introduce the new zonal NePhRO scoring system. The zonal NePhRO score is based on 4 anatomical components that are assigned a score of 1, 2, or 3, and their sum is used to classify renal tumors. The zonal NePhRO scoring system is made up of the (Ne)arness to collecting system, (Ph)ysical location of the tumor in the kidney, (R)adius of the tumor, and (O)rganization of the tumor. In this retrospective study, we evaluated patients exhibiting clinical stage T1a or T1b who underwent open partial nephrectomy performed by 2 genitourinary surgeons. Each renal unit was assigned both a zonal NePhRO score and a RENAL (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior, location relative to polar lines) score, and a blinded reviewer used the same preoperative imaging study to obtain both scores. Additional data points gathered included age, clamp time, complication rate, urine leak rate, intraoperative blood loss, and pathologic tumor size. One hundred sixty-six patients underwent open partial nephrectomy. There were 37 perioperative complications quantitated using the validated Clavien-Dindo system; their occurrence was predicted by the NePhRO score on both univariate and multivariate analyses (P = .0008). Clinical stage, intraoperative blood loss, and tumor diameter were all correlated with the zonal NePhRO score on univariate analysis only. The zonal NePhRO scoring system is a simpler tool that accurately predicts the surgical complexity of a renal lesion. Copyright © 2014 Elsevier Inc. All rights reserved.

A Literature Review of Renal Surgical Anatomy and Surgical Strategies for Partial Nephrectomy.

PubMed

Klatte, Tobias; Ficarra, Vincenzo; Gratzke, Christian; Kaouk, Jihad; Kutikov, Alexander; Macchi, Veronica; Mottrie, Alexandre; Porpiglia, Francesco; Porter, James; Rogers, Craig G; Russo, Paul; Thompson, R Houston; Uzzo, Robert G; Wood, Christopher G; Gill, Inderbir S

2015-12-01

A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). A literature review was conducted. Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Ipsilateral renal function preservation after robot-assisted partial nephrectomy (RAPN): an objective analysis using mercapto-acetyltriglycine (MAG3) renal scan data and volumetric assessment.

PubMed

Zargar, Homayoun; Akca, Oktay; Autorino, Riccardo; Brandao, Luis Felipe; Laydner, Humberto; Krishnan, Jayram; Samarasekera, Dinesh; Stein, Robert J; Kaouk, Jihad H

2015-05-01

To objectively assess ipsilateral renal function (IRF) preservation and factors influencing it after robot-assisted partial nephrectomy (RAPN). Our database was queried to identify patients who had undergone RAPN from 2007 to 2013 and had complete pre- and postoperative mercapto-acetyltriglycine (MAG3) renal scan assessment. The estimated glomerular filtration rate (eGFR) for the operated kidney was calculated by multiplying the percentage of contribution from the renal scan by the total eGFR. IRF preservation was defined as a ratio of the postoperative eGFR for the operated kidney to the preoperative eGFR for the operated kidney. The percentage of total eGFR preservation was calculated in the same manner (postoperative eGFR/preoperative eGFR × 100). The amount of healthy rim of renal parenchyma removed was assessed by deducting the volume of tumour from the volume of the PN specimen assessed on pathology. Multivariable linear regression was used for analysis. In all, 99 patients were included in the analysis. The overall median (interquartile range) total eGFR preservation and IRF preservation for the operated kidney was 83.83 (75.2-94.1)% and 72 (60.3-81)%, respectively (P < 0.01). On multivariable analysis, volume of healthy rim of renal parenchyma removed, warm ischaemia time (WIT) > 30 min, body mass index (BMI) and operated kidney preoperative eGFR were predictive of IRF preservation. Using total eGFR tends to overestimate the degree of renal function preservation after RAPN. This is particularly relevant when studying factors affecting functional outcomes after nephron-sparing surgery. IRF may be a more precise assessment method in this setting. Operated kidney baseline renal function, BMI, WIT >30 min, and amount of resected healthy renal parenchyma represent the factors with a significant impact on the IRF preservation. RAPN provides significant preservation of renal function as shown by objective assessment criteria. © 2014 The Authors. BJU International © 2014 BJU International.

Gingival Crevicular Fluid Turnover Markers in Premenopausal vs Postmenopausal Women receiving Orthodontic Treatment.

PubMed

Bitra, Anusha; Rani, B Jhansi; Agarkar, Sanket S; Parihar, Anuj S; Vynath, Gopinath P; Grover, Shekhar

2017-10-01

Orthodontic treatment is one of the commonly used dental treatments. Orthodontic forces act on the bone by modulating the biomolecules, chiefly the osteoprotegerin (OPG), osteopontin (OPN), receptor activator of nuclear factor kappa-B (RANK), and RANK ligand (RANKL) (OPG ligand). Hormonal changes are known to cause marked alteration in the levels of these biomolecules. Hence, we planned this study to evaluate the response of bone biomarkers in the gingival crevicular fluid (GCF) in postmenopausal women undergoing fixed orthodontic therapy. This study included assessment of 50 subjects who underwent orthodontic treatment from June 2012 to July 2016. All the patients were divided into two study groups with 25 patients in each group: premenopausal group and postmenopausal group. Similar orthodontic wires were used for controlling the forces applied in subjects of both the study groups and their GCF levels of RANKL, and OPN was assessed at baseline and 24 hours after the activation of orthodontic forces. All the results were compiled, assessed, and analyzed by Statistical Package for the Social Sciences software version 16.0. Chi-square test, Student's t-test, and Mann-Whitney U test were used for the assessment of the level of significance. The mean values of RANKL and OPN in the premenopausal and postmenopausal groups were found to be 241.52 and 317.15 pg/μL respectively. The mean values of RANKL at baseline in the premenopausal and postmenopausal groups were found to be 7.15 and 3.84 pg/μL respectively. Nonsignificant results were obtained while comparing mean OPN and RANKL level alteration in between the two study groups. The mean alterations in the GCF levels of bone biomarkers are similar for both premenopausal and postmeno-pausal women. For women with either premenopausal or postmenopausal status, orthodontic treatment appears to be equally safer.

Interleukin-18 deficiency protects against renal interstitial fibrosis in aldosterone/salt-treated mice.

PubMed

Tanino, Akiko; Okura, Takafumi; Nagao, Tomoaki; Kukida, Masayoshi; Pei, Zuowei; Enomoto, Daijiro; Miyoshi, Ken-Ichi; Okamura, Haruki; Higaki, Jitsuo

2016-10-01

Interleukin (IL)-18 is a member of the IL-1 family of cytokines and was described originally as an interferon γ-inducing factor. Aldosterone plays a central role in the regulation of sodium and potassium homoeostasis by binding to the mineralocorticoid receptor and contributes to kidney and cardiovascular damage. Aldosterone has been reported to induce IL-18, resulting in cardiac fibrosis with induced IL-18-mediated osteopontin (OPN). We therefore hypothesized that aldosterone-induced renal fibrosis via OPN may be mediated by IL-18. To verify this hypothesis, we compared mice deficient in IL-18 and wild-type (WT) mice in a model of aldosterone/salt-induced hypertension. IL-18(-/-) and C57BL/6 WT mice were used for the uninephrectomized aldosterone/salt hypertensive model, whereas NRK-52E cells (rat kidney epithelial cells) were used in an in vitro model. In the present in vivo study, IL-18 protein expression was localized in medullary tubules in the WT mice, whereas in aldosterone-infused WT mice this expression was up-regulated markedly in the proximal tubules, especially in injured and dilated tubules. This renal damage caused by aldosterone was attenuated significantly by IL-18 knockout with down-regulation of OPN expression. In the present in vitro study, aldosterone directly induced IL-18 gene expression in renal tubular epithelial cells in a concentration- and time-dependent manner. These effects were inhibited completely by spironolactone. IL-18 may be a key mediator of aldosterone-induced renal fibrosis by inducing OPN, thereby exacerbating renal interstitial fibrosis. Inhibition of IL-18 may therefore provide a potential target for therapeutic intervention aimed at preventing the progression of renal injury. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Euarchontan Opsin Variation Brings New Focus to Primate Origins.

PubMed

Melin, Amanda D; Wells, Konstans; Moritz, Gillian L; Kistler, Logan; Orkin, Joseph D; Timm, Robert M; Bernard, Henry; Lakim, Maklarin B; Perry, George H; Kawamura, Shoji; Dominy, Nathaniel J

2016-04-01

Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The Visual Cycle in the Inner Retina of Chicken and the Involvement of Retinal G-Protein-Coupled Receptor (RGR).

PubMed

Díaz, Nicolás M; Morera, Luis P; Tempesti, Tomas; Guido, Mario E

2017-05-01

The vertebrate retina contains typical photoreceptor (PR) cones and rods responsible for day/night vision, respectively, and intrinsically photosensitive retinal ganglion cells (ipRGCs) involved in the regulation of non-image-forming tasks. Rhodopsin/cone opsin photopigments in visual PRs or melanopsin (Opn4) in ipRGCs utilizes retinaldehyde as a chromophore. The retinoid regeneration process denominated as "visual cycle" involves the retinal pigment epithelium (RPE) or Müller glial cells. Opn4, on the contrary, has been characterized as a bi/tristable photopigment, in which a photon of one wavelength isomerizes 11-cis to all-trans retinal (Ral), with a second photon re-isomerizing it back. However, it is unknown how the chromophore is further metabolized in the inner retina. Nor is it yet clear whether an alternative secondary cycle occurs involving players such as the retinal G-protein-coupled receptor (RGR), a putative photoisomerase of unidentified inner retinal activity. Here, we investigated the role of RGR in retinoid photoisomerization in Opn4x (Xenopus ortholog) (+) RGC primary cultures free of RPE and other cells from chicken embryonic retinas. Opn4x (+) RGCs display significant photic responses by calcium fluorescent imaging and photoisomerize exogenous all-trans to 11-cis Ral and other retinoids. RGR was found to be expressed in developing retina and in primary cultures; when its expression was knocked down, the levels of 11-cis, all-trans Ral, and all-trans retinol in cultures exposed to light were significantly higher and those in all-trans retinyl esters lower than in dark controls. The results support a novel role for RGR in ipRGCs to modulate retinaldehyde levels in light, keeping the balance of inner retinal retinoid pools.

Iatrogenic diaphragmatic lesion: laparoscopic repair.

PubMed

Celia, A; Del Biondo, D; Zaccolini, G; Breda, G

2010-09-01

The increasing use of laparoscopy as first line surgical choice turned the iatrogenic diaphragmatic injury during transperitoneal nephrectomy from an unfrequent complication into a potential risk. We report the laparoscopic management of a iatrogenic diaphragmatic injury during a laparoscopic transperitoneal nephrectomy in a 66-year-old woman with a xantogranulomatous pyelonephritis due to an infected Staghorn stone.

Hypernephroma Presenting with Cutaneous Leukocytoclastic Vasculitis and Lupus Anticoagulant: Resolution after Nephrectomy

PubMed Central

Murray, Nigel P.; Ruíz, Amparo; Reyes, Eduardo

2012-01-01

Hypernephroma can present as a variety of paraneoplastic, nonmetastatic conditions, including vasculitis, and rarely a lupus-type anticoagulant. Nephrectomy leads to the resolution of the systemic complaints. Malignancy, in this case hypernephroma, can present as an immune-mediated paraneoplastic syndrome which resolves after removal of the underlying tumor. PMID:22919534

Predictors of new-onset chronic kidney disease in patients managed surgically for T1a renal cell carcinoma: An Australian population-based analysis.

PubMed

Ahn, Thomas; Ellis, Robert J; White, Victoria M; Bolton, Damien M; Coory, Michael D; Davis, Ian D; Francis, Ross S; Giles, Graham G; Gobe, Glenda C; Hawley, Carmel M; Johnson, David W; Marco, David J T; McStea, Megan; Neale, Rachel E; Pascoe, Elaine M; Wood, Simon T; Jordan, Susan J

2018-05-22

New-onset chronic kidney disease (CKD) following surgical management of kidney tumors is common. This study evaluated risk factors for new-onset CKD after nephrectomy for T1a renal cell carcinoma (RCC) in an Australian population-based cohort. There were 551 RCC patients from the Australian states of Queensland and Victoria included in this study. The primary outcome was new-onset CKD (eGFR <60 mL/min per 1.73 m 2 ) and the secondary outcome was new-onset moderate-severe CKD (<45 mL/min per 1.73 m 2 ). Multivariable logistic regression was used to evaluate associations between patient, tumor and health-service characteristics and these outcomes. Forty percent (219/551) of patients developed new-onset CKD, and 12% (68/551) experienced new-onset moderate-severe CKD. Risk factors for new-onset CKD were age, lower preoperative eGFR, tumor size >20 mm, radical nephrectomy, lower hospital caseloads (<20 cases/year), and rural place of residence. The associations between rural place of residence and low center volume were a consequence of higher radical nephrectomy rates. Risk factors for CKD after nephrectomy generally relate to worse baseline health, or likelihood of undergoing radical nephrectomy. Surgeons in rural centres and hospitals with low caseloads may benefit from formalized integration with specialist centers for continued professional development and case-conferencing, to assist in management decisions. © 2018 Wiley Periodicals, Inc.

Robotic-assisted single-port donor nephrectomy using the da Vinci single-site platform.

PubMed

LaMattina, John C; Alvarez-Casas, Josue; Lu, Irene; Powell, Jessica M; Sultan, Samuel; Phelan, Michael W; Barth, Rolf N

2018-02-01

Although single-port donor nephrectomy offers improved cosmetic outcomes, technical challenges have limited its application to selected centers. Our center has performed over 400 single-port donor nephrectomies. The da Vinci single-site robotic platform was utilized in an effort to overcome the steric, visualization, ergonomic, and other technical limitations associated with the single-port approach. Food and Drug Administration device exemption was obtained. Selection criteria for kidney donation included body mass index <35, left kidney donors, and ≤2 renal arteries. After colonic mobilization using standard single-port techniques, the robotic approach was utilized for ureteral complex and hilar dissection. Three cases were performed using the robotic single-site platform. Average total operative time was 262 ± 42 min including 82 ± 16 min of robotic use. Docking time took 20 ± 10 min. Blood loss averaged 77 ± 64 mL. No intraoperative complications occurred, and all procedures were completed with our standard laparoscopic single-port approach. This is the first clinical experience of robotic-assisted donor nephrectomy utilizing the da Vinci single-site platform. Our experience supported the safety of this approach but found that the technology added cost and complexity without tangible benefit. Development of articulating instruments, energy, and stapling devices will be necessary for increased application of robotic single-site surgery for donor nephrectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

Percutaneous drainage and/or nephrectomy in the treatment of emphysematous pyelonephritis.

PubMed

Mydlo, Jack H; Maybee, Gabrielle J; Ali-Khan, Mustafa M

2003-01-01

To assess the current and past literature relating to the differential treatment of emphysematous pyelonephritis (EPN). Some of the newer literature suggests percutaneous drainage (PCD), as compared to the standard nephrectomy, as a better modality. Since these two may complement each other, we sought to seek indications when to perform each treatment. Medline and MD Consult were used for our journal review. Ten articles, ranging from 1980 to 2000, were chosen, which covered 162 patients. The criteria for selecting these articles were study size (n < 3 were excluded) and non-overlapping of patient information. Patient data was then used to certain risks of the various treatment modalities. Due to the lack of randomization of the studies, it is difficult to say whether PCD is superior to nephrectomy or not. It appears to be that each treatment may complement each other, and that treatment should be individualized based on the severity of the EPN and the medical condition of the patient. PCD though appears to be acceptable for use in the initial phases of the disease. However, long-term data is lacking to corroborate the overall benefit of PCD compared to nephrectomy. PCD could be utilized initially in some cases of EPN if certain conditions exist. This treatment may complement nephrectomy if the need exists, and therefore, treatment may be staged. Truly randomized studies need to be done to determine if one treatment is better than the other, and provide documented long-term follow-up of these patients.

Oncological outcomes after cytoreductive nephrectomy for patients with metastatic renal cell carcinoma with inferior vena caval tumor thrombus.

PubMed

Miyake, Hideaki; Sugiyama, Takayuki; Aki, Ryota; Matsushita, Yuto; Tamura, Keita; Motoyama, Daisuke; Ito, Toshiki; Otsuka, Atsushi

2018-06-01

To evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) involving the inferior vena cava (IVC) who received cytoreductive nephrectomy. This study included 75 consecutive metastatis renal cell carcinoma (mRCC) patients with inferior vena cava (IVC) tumor thrombus undergoing cytoreductive nephrectomy and tumor thrombectomy followed by systemic therapy. Of the 75 patients, 11, 33, 24 and 7 had level I, II, III and IV IVC thrombus, respectively. Following surgical treatment, 25 (group A), 27 (group B) and 23 (group C) received cytokine therapy alone, molecular-targeted therapy alone and both therapies, respectively, as management for metastatic diseases. The median overall survival (OS) of the 75 patients was 16.2 months. No significant differences in OS were noted according to the level of the IVC tumor thrombus. There were no significant differences in OS among groups A, B and C; however, OS in groups B and C was significantly superior to that in group A. Furthermore, multivariate analysis of several parameters identified the following independent predictors of poor OS-elevated C-reactive protein, liver metastasis and postoperative treatment with cytokine therapy alone. The prognosis of mRCC patients with IVC thrombus undergoing cytoreductive nephrectomy may be significantly affected by the type of postoperative systemic therapy rather than the level of the IVC tumor thrombus. Accordingly, cytoreductive nephrectomy should be considered as a major therapeutic option for patients with mRCC involving the IVC, particularly in the era of targeted therapy.

Radiofrequency Ablation of Renal Tumors with an Expandable Multitined Electrode: Results, Complications, and Pilot Evaluation of Cooled Pyeloperfusion for Collecting System Protection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rouviere, Olivier; Badet, Lionel; Murat, Francois Joseph

2008-05-15

The objective of this study was to retrospectively evaluate the results of radiofrequency ablation (RFA) of renal tumors with an impedance-based system using an expandable multitined electrode. Twenty-two patients (30 tumors) were treated with RFA over a 7-year period, percutaneously (16 tumors) or intraoperatively (14 tumors). Follow-up imaging was performed at 1-3, 6, and 12 months and yearly thereafter. Twenty-seven of 30 tumors (19/22 patients) showed no residual tumor on the first imaging control. Two residual tumors were successfully ablated by a second RFA procedure. Our mean follow-up period was 35 months (range, 3-84 months). Two tumors that had beenmore » completely ablated based on imaging criteria recurred 11 and 48 months after RFA. One was treated by partial nephrectomy. The other one was not treated because the patient developed bone metastases. One patient had nephrectomy because of an RFA-induced ureteropelvic junction stricture. Nine patients (11 sessions) had a pyeloperfusion of cooled saline during RFA. None developed symptomatic complications, even though in three patients the ablation zone extended to the closest calyx (3-5 mm from the tumor). We conclude that RFA of renal tumors is promising, but serious complications to the collecting system must be taken into consideration. Prophylactic per-procedural cooling of the collecting system is feasible but needs further assessment.« less

Intravesical ligation as a new technique to manage a refluxing native ureter without simultaneous nephrectomy in renal transplantation.

PubMed

Guzmán, J A

2012-12-01

This article aims to describe an original technique to correct refluxing native ureters observed during a prerenal transplantation study. The correction is performed by intravesical ligation of the native refluxing ureters at the same time as renal transplantation without simultaneous nephrectomy. Between January 2004 and December 2010 we performed intravesical ligation of a refluxing ureter simultaneous with a transplantation procedure without a concomittant native nephrectomy in 12 of 345 subjects (3.47%). The 8 bilateral and 4 unilateral ligations were performed on 11 cadaveric and 1 living-related nonidentical donor transplantations. The implantation of the kidney donor ureter was performed anatomically in the bladder trigone through a transvesical ureteroneocystostomy with a transmural, submucosal antireflux tunnel. Early and late postoperative recovery was satisfactory in all patients. There was no documented kidney area pain, proven urinary tract infection, morbidity or mortality attributed to the procedure. Intravesical ligation is a practical technique to manage vesicoureteral reflux into the native ureters simultaneously with the ureteral implantation of the kidney donor in a single surgical renal transplant procedure without native kidney nephrectomy. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of Pfannenstiel or Extended Iliac Port Site Kidney Extraction in Laparoscopic Donor Nephrectomy: Do We Have Consensus?

PubMed

Iemsupakkul, Paiboon; Kongchareonsombat, Wisoot; Kijvikai, Kittinut

2017-04-01

Our objective was to compare the outcomes of the different extraction sites between extended iliac port site incision and Pfannenstiel incision during laparoscopic donor nephrectomy. We prospectively evaluated patients who underwent laparoscopic donor nephrectomy from June 2014 to March 2015 at our institution. Perioperative parameters were included, with particular reference to warm ischemic time. The other parameters recorded included operative time, blood loss, hospital stay, analgesic requirement, and cosmetic results. We analyzed a total of 41 patients. Kidney retrieval site of each patient was made randomly. Extraction sites were done by using extended iliac port site incisions in 23 patients and by Pfannenstiel incision in 18 patients. Mean warm ischemic time was 4.09 minutes with extended iliac port site incision versus 4.94 minutes with Pfannenstiel incision (P = .04). Mean operative time, blood loss, hospital stay, and analgesic requirements were comparable between the 2 groups. Mean cosmetic score was 10.39 with extended iliac port site versus 12.06 with Pfannenstiel incision. Extraction with extended iliac port site incision had significantly less warm ischemic time than Pfannenstiel incision in laparoscopic donor nephrectomy. It was also not inferior to Pfannenstiel incision regarding the other.

Effect of renin-angiotensin system on sodium intake.

PubMed Central

Chiaraviglio, E

1976-01-01

1. Water and saline intake was measured in rats depleted of Na by I.P. dialysis. Na intake was prevented 180 min but not 60-90 min after bilateral nephrectomy. Unilateral nephrectomy as well as ureteral ligature had no effect on Na intake. 2. Renin (3u.) injected I.P. re-established the Na appetite abolished by nephrectomy. 3. Angiotensin I (5 ng) or II (5-40 ng) injected into the 3rd ventricle, also restored the Na intake and this effect was dose-dependent. 4. The angiotensin converting-enzyme inhibitor Sq 20,881 (1 mg/kg) inhibited the effect of AI but not that of AII in restoring Na intake. 5. It is concluded that the kidneys might play a role in the regulation of Na intake through the renin-angiotensin system. PMID:1255521

Duplex System with Ectopic Ureter Opens into the Posterior Urethra: Case Report.

PubMed

Milicevic, Snjezana; Bijelic, Radojka; Krivokuca, Vladimir; Jakovljevic, Branislava

2018-04-01

Duplicated ureter or Duplex Collecting System is a congenital condition in which the ureteric bud, the embryological origin of the ureter, arises twice, resulting in two ureters draining a single kidney. This congenital anomaly is rare, and even rarer when the duplex system with ectopic ureter is present. This type of congenital anomaly is even more rarely diagnosed and surgically treated in adulthood. This case report presents a case of a 32-year-old male, who had a duplex collecting system with two ureters on the left side. Ectopic ureter, draining the upper pole of the left kidney, opened into the posterior urethra. In our patient, taking into account the clinical perspective, the renal tissue damaging of the upper pole which was not functional, partial nephrectomy and ureterectomy was successfully performed.

Beware! A simple renal cyst could be a hydatid cyst.

PubMed

Sehgal, Nidhi; Priyadarshi, Vinod

2017-01-01

Kidney is one of the most common sites for the cyst formation in the body, and the management of simple cysts is required entirely for its symptoms and complications. Surgical decortication is an established treatment for a large and symptomatic simple renal cyst. On the other hand, hydatid cysts of the kidney are usually multiloculated complex or calcified cysts and are quite rare. Their surgical treatment also differs and requires complete excision with pericystectomy or partial/complete nephrectomy depending upon residual functional parenchyma, using extreme caution to avoid spillage, recurrence or development of severe anaphylactic shock. A simple cyst harboring a hydatid cyst is highly uncommon and quite dangerous; as if not diagnosed preoperatively, it can create huge trouble for both the patient and the operating surgeon which happened in the present case.

Experience with extracorporeal renal operations and autotransplantation in the management of complicated urologic disorders.

PubMed

Novick, A C; Straffon, R A; Stewart, B H

1981-07-01

Renal autotransplantation with or without an extracorporeal renal operation was performed 45 times upon 43 patients. Twenty-one patients underwent renal autotransplantation as surgical treatment for renovascular hypertension, all of whom are cured or have improved postoperatively. Sixteen renal autotransplants were performed upon 14 patients with extensive ureteral disease, 14 of which were successful. Six patients with carcinoma centrally located in a solitary kidney underwent extracorporeal partial nephrectomy and autotransplantation. Three of these patients are alive with functioning autografts and are tumor-free from one to five years postoperatively. Two patients with multiple recurrent renal calculi were successfully treated by extracorporeal pyelolithotomy and autotransplantation with pyelovesicostomy. An extracorporeal renal operation and autotransplantation can provide the best solution for selected urologic problems not correctable by conventional methods.

Aortic calcification burden predicts deterioration of renal function after radical nephrectomy.

PubMed

Fukushi, Ken; Hatakeyama, Shingo; Yamamoto, Hayato; Tobisawa, Yuki; Yoneyama, Tohru; Soma, Osamu; Matsumoto, Teppei; Hamano, Itsuto; Narita, Takuma; Imai, Atsushi; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Terayama, Yuriko; Funyu, Tomihisa; Ohyama, Chikara

2017-02-06

Radical nephrectomy for renal cell carcinoma (RCC) is a risk factor for the development of chronic kidney disease (CKD), and the possibility of postoperative deterioration of renal function must be considered before surgery. We investigated the contribution of the aortic calcification index (ACI) to the prediction of deterioration of renal function in patients undergoing radical nephrectomy. Between January 1995 and December 2012, we performed 511 consecutive radical nephrectomies for patients with RCC. We retrospectively studied data from 109 patients who had regular postoperative follow-up of renal function for at least five years. The patients were divided into non-CKD and pre-CKD based on a preoperative estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m 2 or <60 mL/min/1.73 m 2 , respectively. The ACI was quantitatively measured by abdominal computed tomography before surgery. The patients in each group were stratified between low and high ACIs. Variables such as age, sex, comorbidities, and pre- and postoperative renal function were compared between patients with a low or high ACI in each group. Renal function deterioration-free interval rates were evaluated by Kaplan-Meier analysis. Factors independently associated with deterioration of renal function were determined using multivariate analysis. The median age, preoperative eGFR, and ACI in this cohort were 65 years, 68 mL/min/1.73 m 2 , and 8.3%, respectively. Higher ACI (≥8.3%) was significantly associated with eGFR decline in both non-CKD and pre-CKD groups. Renal function deterioration-free interval rates were significantly lower in the ACI-high than ACI-low strata in both of the non-CKD and pre-CKD groups. Multivariate analysis showed that higher ACI was an independent risk factor for deterioration of renal function at 5 years after radical nephrectomy. Aortic calcification burden is a potential predictor of deterioration of renal function after radical nephrectomy. This study was registered as a clinical trial: UMIN000023577.