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Sample records for resection tissue reveals

  1. Validation of a nonrigid registration framework that accommodates tissue resection

    NASA Astrophysics Data System (ADS)

    Risholm, Petter; Samset, Eigil; Wells, William, III

    2010-03-01

    We present a 3D extension and validation of an intra-operative registration framework that accommodates tissue resection. The framework is based on the bijective Demons method, but instead of regularizing with the traditional Gaussian smoother, we apply an anisotropic diffusion filter with the resection modeled as a diffusion sink. The diffusion sink prevents unwanted Demon forces that originates from the resected area from diffusing into the surrounding area. Another attractive property of the diffusion sink is the resulting continuous deformation field across the diffusion sink boundary, which allows us to move the boundary of the diffusion sink without changing values in the deformation field. The area of resection is estimated by a level-set method evolving in the space of image intensity disagreements in the intra-operative image domain. A product of using the bijective Demons method is that we can also provide an accurate estimate of the resected tissue in the preoperative image space. Validation of the proposed method was performed on a set of 25 synthetic images. Our experiments show a significant improvement in accommodating resection using the proposed method compared to two other Demons based methods.

  2. Injury Response of Resected Human Brain Tissue In Vitro.

    PubMed

    Verwer, Ronald W H; Sluiter, Arja A; Balesar, Rawien A; Baaijen, Johannes C; de Witt Hamer, Philip C; Speijer, Dave; Li, Yichen; Swaab, Dick F

    2015-07-01

    Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by resection (interruption of the circulation) and aggravated by the preparation of slices (severed neuronal and glial processes and blood vessels) reflect the reaction of human brain tissue to severe injury. We investigated this process using immunocytochemical markers, reverse transcriptase quantitative polymerase chain reaction and Western blot analysis. Essential features were rapid shrinkage of neurons, loss of neuronal marker expression and proliferation of reactive cells that expressed Nestin and Vimentin. Also, microglia generally responded strongly, whereas the response of glial fibrillary acidic protein-positive astrocytes appeared to be more variable. Importantly, some reactive cells also expressed both microglia and astrocytic markers, thus confounding their origin. Comparison with post-mortem human brain tissue obtained at rapid autopsies suggested that the reactive process is not a consequence of epilepsy.

  3. Soft tissue sarcoma resection volume associated with wound-healing complications.

    PubMed

    Geller, David S; Hornicek, Francis J; Mankin, Henry J; Raskin, Kevin A

    2007-06-01

    Limb-salvage surgery has become the standard of care for most soft tissue sarcomas. While primary closure is often possible, it is frequently complicated by wound-healing complications in the setting of previously irradiated tissue and surgical wounds closed under tension. We sought to identify a relationship between the volume of resected soft tissue and the rate of wound-healing complications. We retrospectively reviewed 108 patients who were treated over a 17-month period for soft-tissue sarcomas using limb-salvage methods. Of these, 87 patients were treated with primary wound closure and 21 patients underwent primary muscle flap closure at the time of wide surgical excision. Of the 87 patients treated with primary wound closure, the mean volume of resected tissue in the group with wound-healing complications was greater than that the group that healed without complications. The mean volume of resected tissue in the group with wound-healing complications was 919 cm3 +/- 1173 cm3 and the mean volume of resected tissue in the group without wound-healing complications was 456 cm3 +/- 704 cm3. Mean volume of resected tissue in the group of patients treated with primary flap coverage was 1908 cm3, over twice as large as the mean volume of resected tissue in the group of patients treated with primary closure.

  4. Hyperplasia vs hypertrophy in tissue regeneration after extensive liver resection

    PubMed Central

    Marongiu, Fabio; Marongiu, Michela; Contini, Antonella; Serra, Monica; Cadoni, Erika; Murgia, Riccardo; Laconi, Ezio

    2017-01-01

    AIM To address to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. METHODS The ability of the liver to regenerate is remarkable on both clinical and biological grounds. Basic mechanisms underlying this process have been intensively investigated. However, it is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system. We were able to follow the fate of single transplanted hepatocytes during the regenerative response elicited by 2/3 partial surgical hepatectomy (PH) in rats. Clusters of transplanted cells were 3D reconstructed and their size distribution was evaluated over time after PH. RESULTS Liver size and liver DNA content were largely recovered 10 d post-PH, as expected (e.g., total DNA/liver/100 g b.w. was 6.37 ± 0.21 before PH and returned to 6.10 ± 0.36 10 d after PH). Data indicated that about 2/3 of the original residual hepatocytes entered S-phase in response to PH. Analysis of cluster size distribution at 24, 48, 96 h and 10 d after PH revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes increased at 24 h (248.50 μm2 ± 7.82 μm2, P = 0.0015), but returned to control values throughout the regenerative process (up to 10 d post-PH, 197.9 μm2 ± 6.44 μm2, P = 0.11). A sizeable fraction of the remnant hepatocyte population does not participate actively in tissue mass restoration. CONCLUSION Hyperplasia stands as the major mechanism contributing to liver mass restoration after PH, with hypertrophy playing a transient role in the process. PMID:28348481

  5. Clinical study of ex vivo photoacoustic imaging in endoscopic mucosal resection tissues

    NASA Astrophysics Data System (ADS)

    Lim, Liang; Streutker, Catherine J.; Marcon, Norman; Cirocco, Maria; Lakovlev, Vladimir V.; DaCosta, Ralph; Foster, F. S.; Wilson, Brian C.

    2015-03-01

    Accurate endoscopic detection and dysplasia in patients with Barrett's esophagus (BE) remains a major unmet clinical need. Current diagnosis use multiple biopsies under endoscopic image guidance, where up to 99% of the tissue remains unsampled, leading to significant risk of missing dysplasia. We conducted an ex vivo clinical trial using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) with known high-grade dysplasia for the purpose of characterizing the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia detection and therapeutic guidance. EMR tissues were mounted immediately on an agar layer and covered with ultrasound gel. Digital photography guided the placement of the PAI transducer (40 MHz center frequency). The luminal side of the specimen was scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, 824, 850 and 970 nm. Acoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with H and E staining. Analysis consisted of co-registration and correlation between the intrinsic PAI features and the histological images. The initial PAI + ultrasound images from 8 BE patients have demonstrated the technical feasibility of this approach and point to the potential of PAI to reveal the microvascular pattern within EMR specimens. There are several technical factors to be considered in rigorous interpretation of the PAI characteristics, including the loss of blood from the ex vivo specimens and the limited depth penetration of the photoacoustic signal.

  6. Resected Brain Tissue, Seizure Onset Zone and Quantitative EEG Measures: Towards Prediction of Post-Surgical Seizure Control

    PubMed Central

    Andrzejak, Ralph G.; Hauf, Martinus; Pollo, Claudio; Müller, Markus; Weisstanner, Christian; Wiest, Roland; Schindler, Kaspar

    2015-01-01

    Background Epilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure. Methods Despite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels. Results In patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied. Conclusions We conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent

  7. Tissue expander placement and adjuvant radiotherapy after surgical resection of retroperitoneal liposarcoma offers improved local control

    PubMed Central

    Park, Hyojun; Lee, Sanghoon; Kim, BoKyong; Lim, Do Hoon; Choi, Yoon-La; Choi, Gyu Seong; Kim, Jong Man; Park, Jae Berm; Kwon, Choon Hyuck David; Joh, Jae-Won; Kim, Sung Joo

    2016-01-01

    Abstract Given that retroperitoneal liposarcoma (LPS) is extremely difficult to completely resect, and has a relatively high rate of recurrence, radiotherapy (RT) is the treatment of choice after surgical resection. However, it is difficult to obtain a sufficient radiation field because of the close proximity of surrounding organs. We introduce the use of tissue expanders (TEs) after LPS resection in an attempt to secure a sufficient radiation field and to improve recurrence-free survival. This study is a retrospective review of 53 patients who underwent surgical resection of LPS at Samsung Medical Center between January 1, 2005, and December 31, 2012, and had no residual tumor detected 2 months postoperatively. The median follow-up period was 38.9 months. Patients were divided into 3 groups. Those in group 1 (n = 17) had TE inserted and received postoperative RT. The patients in group 2 (n = 9) did not have TE inserted and received postoperative RT. Finally, those in group 3 (n = 27) did not receive postoperative RT. Multivariate analysis was performed to identify the risk factors associated with recurrence-free survival within 3 years. Younger age, history of LPS treatment, and RT after TE insertion (group 1 vs group 2 or 3) were significantly favorable factors influencing 3-year recurrence-free survival. TE insertion after LPS resection is associated with increased 3-year recurrence-free survival, most likely because it allows effective delivery of postoperative RT. PMID:27512857

  8. Tissue expander placement and adjuvant radiotherapy after surgical resection of retroperitoneal liposarcoma offers improved local control.

    PubMed

    Park, Hyojun; Lee, Sanghoon; Kim, BoKyong; Lim, Do Hoon; Choi, Yoon-La; Choi, Gyu Seong; Kim, Jong Man; Park, Jae Berm; Kwon, Choon Hyuck David; Joh, Jae-Won; Kim, Sung Joo

    2016-08-01

    Given that retroperitoneal liposarcoma (LPS) is extremely difficult to completely resect, and has a relatively high rate of recurrence, radiotherapy (RT) is the treatment of choice after surgical resection. However, it is difficult to obtain a sufficient radiation field because of the close proximity of surrounding organs. We introduce the use of tissue expanders (TEs) after LPS resection in an attempt to secure a sufficient radiation field and to improve recurrence-free survival.This study is a retrospective review of 53 patients who underwent surgical resection of LPS at Samsung Medical Center between January 1, 2005, and December 31, 2012, and had no residual tumor detected 2 months postoperatively. The median follow-up period was 38.9 months.Patients were divided into 3 groups. Those in group 1 (n = 17) had TE inserted and received postoperative RT. The patients in group 2 (n = 9) did not have TE inserted and received postoperative RT. Finally, those in group 3 (n = 27) did not receive postoperative RT. Multivariate analysis was performed to identify the risk factors associated with recurrence-free survival within 3 years. Younger age, history of LPS treatment, and RT after TE insertion (group 1 vs group 2 or 3) were significantly favorable factors influencing 3-year recurrence-free survival.TE insertion after LPS resection is associated with increased 3-year recurrence-free survival, most likely because it allows effective delivery of postoperative RT.

  9. Selective tissue elevation by pressure injection (STEP) facilitates endoscopic mucosal resection (EMR).

    PubMed

    Kähler, Georg F B A; Sold, Moritz S; Post, Stefan; Fischer, Klaus; Enderle, Markus D

    2007-01-01

    Endoscopic mucosal resection and endoscopic submucosal dissection have become more common in treatment of flat superficial tumors of the gastrointestinal tract. Submucosal injection is used to try to avoid complications and improve the technical feasibility of the procedure. However, the method has its limitations, particularly when treating extensive flat tumors in the colon. The water-jet dissector has already demonstrated its capacity for selective cutting with the dissection of parenchymatous. This chapter addresses a new indication, transmucosal mucosal elevation, together with first clinical results. After carrying out animal experiments into the physical properties using animal preparations and freshly resected human specimens from operations, our work group investigated and compared the applicability of the procedure using different carrier fluids. Six test substances-hydroxyethyl starch (HES), Gelafusal, Infukoll, Glucose 50 und isotonic saline solution-were injected into six anesthetized pigs; the height of the submucosal fluid cushion created by the injection was measured endosonographically over a period of 45 minutes. Endoscopic mucosal resection was subsequently carried out, and the resected specimen together with the area it was taken from were assessed histologically. Using commercially available NaCl cartridges, applied by the way of endocapillaries, 18 lesions were elevated in a series of 12 patients and subsequently resected endoscopically. All investigated substances could be applied without difficulty using the Helix HydroJet (Erbe Elektromedizin GmbH, Waldhörnle-Str., Tübingen, Germany). The plasma expanders (HES and Gelafundin 4%, B. Braun Melsungen AG, Melsungen, Germany) produced longer lasting fluid cushions than the isotonic solutions. Mucosal resections could be carried out in all cases with all of the solutions. Histological investigation confirmed the selective nature of the fluid accumulation in the submucosal tissue, which spared

  10. Early postnatal rat ventricle resection leads to long‐term preserved cardiac function despite tissue hypoperfusion

    PubMed Central

    Zogbi, Camila; Saturi de Carvalho, Ana E. T.; Nakamuta, Juliana S.; Caceres, Viviane de M.; Prando, Silvana; Giorgi, Maria C. P.; Rochitte, Carlos E.; Meneghetti, Jose C.; Krieger, Jose E.

    2014-01-01

    Abstract One‐day‐old mice display a brief capacity for heart regeneration after apex resection. We sought to examine this response in a different model and to determine the impact of this early process on long‐term tissue perfusion and overall cardiac function in response to stress. Apical resection of postnatal rats at day 1 (P1) and 7 (P7) rendered 18 ± 1.0% and 16 ± 1.3% loss of cardiac area estimated by magnetic resonance imaging (MRI), respectively (P > 0.05). P1 was associated with evidence of cardiac neoformation as indicated by Troponin I and Connexin 43 expression at 21 days postresection, while in the P7 group mainly scar tissue replacement ensued. Interestingly, there was an apparent lack of uniform alignment of newly formed cells in P1, and we detected cardiac tissue hypoperfusion for both groups at 21 and 60 days postresection using SPECT scanning. Direct basal cardiac function at 60 days, when the early lesion is undetectable, was preserved in all groups, whereas under hemodynamic stress the degree of change on LVDEP, Stroke Volume and Stroke Work indicated diminished overall cardiac function in P7 (P < 0.05). Furthermore, the End‐Diastolic Pressure–Volume relationship and increased interstitial collagen deposition in P7 is consistent with increased chamber stiffness. Taken together, we provide evidence that early cardiac repair response to apex resection in rats also leads to cardiomyocyte neoformation and is associated to long‐term preservation of cardiac function despite tissue hypoperfusion. PMID:25168870

  11. Parthenogenesis in human oocytes that were collected from resected ovarian tissue and matured in vitro.

    PubMed

    Lee, Ho-Joon; Teixeira, Jose

    2009-01-01

    Currently, a major hurdle in the progress of human embryonic stem (hES) cell research is the lack of human oocytes with which to perform experiments. The collection process is a logistical and ethical challenge and usually involves the use of excess oocytes donated after assisted reproduction procedures. We collected resected human ovarian tissue after routine surgical procedures. Oocytes were isolated from the tissue and matured in vitro to the meiosis II (MII) stage, when the first polar body is extruded. With the large antral and smaller preantral follicles, the efficiencies of the maturation were nearly 50% and 25%, respectively. The quality of the matured oocytes was assessed by inducing parthenogenesis and >50% of the in vitro matured oocytes were competent enough to develop pronuclei and 33% developed at least to the two-cell stage 48 h after activation. Parthenotes continued to develop by 72 h but with significant blastomere fragmentation. These results provide evidence that resected ovarian tissue, which is normally discarded, may be a suitable alternative source for oocytes in hES cell research.

  12. Virtual Cortical Resection Reveals Push-Pull Network Control Preceding Seizure Evolution.

    PubMed

    Khambhati, Ankit N; Davis, Kathryn A; Lucas, Timothy H; Litt, Brian; Bassett, Danielle S

    2016-09-07

    In ∼20 million people with drug-resistant epilepsy, focal seizures originating in dysfunctional brain networks will often evolve and spread to surrounding tissue, disrupting function in otherwise normal brain regions. To identify network control mechanisms that regulate seizure spread, we developed a novel tool for pinpointing brain regions that facilitate synchronization in the epileptic network. Our method measures the impact of virtually resecting putative control regions on synchronization in a validated model of the human epileptic network. By applying our technique to time-varying functional networks, we identified brain regions whose topological role is to synchronize or desynchronize the epileptic network. Our results suggest that greater antagonistic push-pull interaction between synchronizing and desynchronizing brain regions better constrains seizure spread. These methods, while applied here to epilepsy, are generalizable to other brain networks and have wide applicability in isolating and mapping functional drivers of brain dynamics in health and disease.

  13. Volumetric x-ray coherent scatter imaging of cancer in resected breast tissue: a Monte Carlo study using virtual anthropomorphic phantoms

    NASA Astrophysics Data System (ADS)

    Lakshmanan, Manu N.; Harrawood, Brian P.; Samei, Ehsan; Kapadia, Anuj J.

    2015-08-01

    Breast cancer patients undergoing surgery often choose to have a breast conserving surgery (BCS) instead of mastectomy for removal of only the breast tumor. If post-surgical analysis such as histological assessment of the resected tumor reveals insufficient healthy tissue margins around the cancerous tumor, the patient must undergo another surgery to remove the missed tumor tissue. Such re-excisions are reported to occur in 20%-70% of BCS patients. A real-time surgical margin assessment technique that is fast and consistently accurate could greatly reduce the number of re-excisions performed in BCS. We describe here a tumor margin assessment method based on x-ray coherent scatter computed tomography (CSCT) imaging and demonstrate its utility in surgical margin assessment using Monte Carlo simulations. A CSCT system was simulated in Geant4 and used to simulate two virtual anthropomorphic CSCT scans of phantoms resembling surgically resected tissue. The resulting images were volume-rendered and found to distinguish cancerous tumors embedded in complex distributions of adipose and fibroglandular breast tissue (as is expected in the breast). The images exhibited sufficient spatial and spectral (i.e. momentum transfer) resolution to classify the tissue in any given voxel as healthy or cancerous. ROC analysis of the classification accuracy revealed an area under the curve of up to 0.97. These results indicate that coherent scatter imaging is promising as a possible fast and accurate surgical margin assessment technique.

  14. Surgical resection with adjuvant brachytherapy in soft tissue sarcoma of the extremity – a case report

    PubMed Central

    Łyczek, Jarosław; Kowalik, Łukasz

    2012-01-01

    Purpose Surgery is the major therapeutic method in soft tissue sarcomas of the extremity (E-STS). Treatment of large high-grade tumours, which resection cannot be performed with a wide safe margin, should include complementary radiation and/or chemo-therapy. Hopefully, the use of adjuvant brachytherapy will improve the prognosis of E-STS. Case description After a long process of diagnosing a tumour in the medial compartment of the thigh, a 65-year-old woman with diagnosed synovial sarcoma underwent a surgery. Compartment resection was performed and the tumour was removed with a 10 mm safety margin of healthy tissue. Adjuvant brachytherapy was delivered with 192Ir (MicroSelectron, Nucletron Electa Group, Stockholm, Sweden®) with 10 Ci of nominal activity to a dose of 55 Gy in 16 days because of large tumour size (99 × 78 × 73 mm) and its proximity to the neurovascular bundle. No complications were reported. The patient was discharged from the hospital on the 28th day after the surgery. The wound healed without any complications and the outpatient follow-up is being continued. Discussion Adjuvant brachytherapy is rarely used after surgical treatment due to its limited accessibility in hospitals with surgical and orthopaedic departments. There are numerous publications proving positive influence of brachytherapy on local control and decreased number of recurrences. The recurrence-free survival time also increased significantly, however no direct impact on the number of distant metastases was found. Treatment is well tolerated and short. The complication rate varies between centres from 5 to 30%. The most common adverse effects include: peripheral neuropathy, skin necrosis and osteonecrosis of the long bones. Conclusions Treatment of large soft tissue sarcomas of the extremity (E-STS) should include combination of surgical intervention and external beam radiotherapy or brachytherapy. Adjuvant brachytherapy improves local control rate up to 78%, is well tolerated and

  15. Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable Soft Tissue Sarcomas

    SciTech Connect

    Yoon, Sam S.; Duda, Dan G.; Karl, Daniel L.; Kim, Tae-Min; Kambadakone, Avinash R.; Chen, Yen-Lin; Rothrock, Courtney; Rosenberg, Andrew E.; Nielsen, G. Petur; Kirsch, David G.; Choy, Edwin; Harmon, David C.; Hornicek, Francis J.; Dreyfuss, Jonathan; Ancukiewicz, Marek; and others

    2011-11-15

    Purpose: Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Methods and Materials: Patients with {>=}5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. Results: The 20 patients had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in {>=}80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62-72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence. Conclusions: The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants

  16. Normalization of gene expression measurement of tissue samples obtained by transurethral resection of bladder tumors

    PubMed Central

    Pop, Laura A; Pileczki, Valentina; Cojocneanu-Petric, Roxana M; Petrut, Bogdan; Braicu, Cornelia; Jurj, Ancuta M; Buiga, Rares; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

    2016-01-01

    Background Sample processing is a crucial step for all types of genomic studies. A major challenge for researchers is to understand and predict how RNA quality affects the identification of transcriptional differences (by introducing either false-positive or false-negative errors). Nanotechnologies help improve the quality and quantity control for gene expression studies. Patients and methods The study was performed on 14 tumor and matched normal pairs of tissue from patients with bladder urothelial carcinomas. We assessed the RNA quantity by using the NanoDrop spectrophotometer and the quality by nano-microfluidic capillary electrophoresis technology provided by Agilent 2100 Bioanalyzer. We evaluated the amplification status of three housekeeping genes and one small nuclear RNA gene using the ViiA 7 platform, with specific primers. Results Every step of the sample handling protocol, which begins with sample harvest and ends with the data analysis, is of utmost importance due to the fact that it is time consuming, labor intensive, and highly expensive. High temperature of the surgical procedure does not affect the small nucleic acid sequences in comparison with the mRNA. Conclusion Gene expression is clearly affected by the RNA quality, but less affected in the case of small nuclear RNAs. We proved that the high-temperature, highly invasive transurethral resection of bladder tumor procedure damages the tissue and affects the integrity of the RNA from biological specimens. PMID:27330317

  17. Narrowing Resection of Parametrial Tissues Is Feasible in Low-Risk Cases of Stage IA2-IB1 Cervical Cancer

    PubMed Central

    Li, Xue-Lian; Liu, Xiao-Xia; Cao, Guan-Shu; Ju, Dan-Dan; Jiang, Hua

    2016-01-01

    BACKGROUND: Radical hysterectomy with pelvic lymphadenectomy is the standard surgical treatment for patients with stage IA2-IB1 cervical cancer, but the wide excision increases the complications. OBJECTIVE: To analyze the feasibility of narrowing resection of parametrial tissues in stage IA2-IB1 cervical cancer. STUDY DESIGN: Retrospectively analyzed the pathological and clinical data of patients with stage IA2-IB1 cervical cancer who received radical hysterectomy with pelvic lymphadenectomy in OB/GYN Hospital, Fudan University, China from Jan 2008 to Dec 2011. The affected factors of parametrial metastases and outcomes were discussed. The single factor analysis was made with χ2 test, and the relationship of the resection width of parametrial tissues and the patients' outcomes was analyzed with χ2 test and log-rank. P-values <0.05 were considered statistically significant. RESULTS: There were 31 cases recurred, 26 cases died of cervical cancer in 513 patients during the follow-up period (from 2 months to 66 months, averaged 39 months). The low-risk factors included diameter of tumor ≤2cm, depth of cervical myometrial invasion<1/2 and without lymph vascular involvement. There were no parametrial metastases in cases with all three low-risk factors. Whether the resection width of parametrial tissues ≥3cm or not had no statistically significant effect on progression free survival (PFS) or overall survival (OS) of low-risk patients. D2-40 and CD31 were related with parametrial metastases, but not with recurrence or outcomes. CONCLUSIONS: The resection width of parametrial tissues has no effect on PFS and OS of low-risk patients, and narrowing resection of parametrial tissues (<3cm) is feasible. PMID:27471564

  18. A Dark-field Scanning In Situ Spectroscopy Platform for Broadband Imaging of Resected Tissue

    PubMed Central

    Krishnaswamy, Venkataramanan; Laughney, Ashley M.; Paulsen, Keith D.; Pogue, Brian W.

    2012-01-01

    A dark-field geometry spectral imaging system is presented to raster-scan thick tissue samples in situ in 1.5cm square sections, recovering full spectra from each 100 microns diameter pixel. This spot size provides adequate resolution for wide field scanning, while also facilitating scatter imaging without requiring sophisticated light-tissue transport modeling. The system is demonstrated showing accurate estimation of localized scatter parameters and the potential to recover absorption-based contrast from broadband reflectance data measured from 480nm up to 750nm in tissue phantoms. Results obtained from xenograft pancreas tumors show the ability to quantitatively image changes in localized scatter response in this fast imaging geometry. The polychromatic raster scan design allows the rapid scanning necessary for use in surgical/clinical applications where timely decisions are required about tissue pathology. PMID:21593932

  19. Investigation of water spray to reduce collateral thermal damage during laser resection of soft tissue

    NASA Astrophysics Data System (ADS)

    Theisen-Kunde, D.; Wolken, H.; Ellebrecht, D.; Danicke, V.; Wurster, L.; Kleemann, M.; Birngruber, R.

    2013-06-01

    To reduce unwanted collateral thermal damage to surrounding tissue and organs during laparoscopic laser dissection (cw, wavelength: 1.9μm) of porcine liver water spray was used. Size and amount of the produced water droplets of the water spray were photographed by short time imaging and analyzed by imaging software. At in vivo measurements on fresh porcine liver the depth of thermal damage was reduced by 85 % with water spray and the lateral size of thermal damage at the tissue surface could be reduced by 67%. This results show that especially for laparoscopic laser surgery water spray application might be a useful tool to avoid unwanted collateral thermal damage.

  20. Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

    SciTech Connect

    Nichols, Romaine C.; Huh, Soon N.; Prado, Karl L.; Yi, Byong Y.; Sharma, Navesh K.; Ho, Meng W.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Li, Zuofeng; Regine, William F.

    2012-05-01

    Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

  1. Classification of 27 Tumor-Associated Antigens by Histochemical Analysis of 36 Freshly Resected Lung Cancer Tissues

    PubMed Central

    Kurosawa, Gene; Sugiura, Mototaka; Hattori, Yoshinobu; Tsuda, Hiroyuki; Kurosawa, Yoshikazu

    2016-01-01

    In previous studies, we identified 29 tumor-associated antigens (TAAs) and isolated 488 human monoclonal antibodies (mAbs) that specifically bind to one of the 29 TAAs. In the present study, we performed histochemical analysis of 36 freshly resected lung cancer tissues by using 60 mAbs against 27 TAAs. Comparison of the staining patterns of tumor cells, bronchial epithelial cells, and normal pulmonary alveolus cells and interalveolar septum allowed us to determine the type and location of cells that express target molecules, as well as the degree of expression. The patterns were classified into 7 categories. While multiple Abs were used against certain TAAs, the differences observed among them should be derived from differences in the binding activity and/or the epitope. Thus, such data indicate the versatility of respective clones as anti-cancer drugs. Although the information obtained was limited to the lung and bronchial tube, bronchial epithelial cells represent normal growing cells, and therefore, the data are informative. The results indicate that 9 of the 27 TAAs are suitable targets for therapeutic Abs. These 9 Ags include EGFR, HER2, TfR, and integrin α6β4. Based on our findings, a pharmaceutical company has started to develop anti-cancer drugs by using Abs to TfR and integrin α6β4. HGFR, PTP-LAR, CD147, CDCP1, and integrin αvβ3 are also appropriate targets for therapeutic purposes. PMID:27834817

  2. Radiation Therapy for Control of Soft-Tissue Sarcomas Resected With Positive Margins

    SciTech Connect

    DeLaney, Thomas F. . E-mail: tdelaney@partners.org; Kepka, Lucyna; Goldberg, Saveli I.; Hornicek, Francis J.; Gebhardt, Mark C.; Yoon, Sam S.; Springfield, Dempsey S.; Raskin, Kevin A.; Harmon, David C.; Kirsch, David G.; Mankin, Henry J.; Rosenberg, Andrew E.; Nielsen, G. Petur; Suit, Herman D.

    2007-04-01

    Purpose: Positive margins (PM) remain after surgery in some soft-tissue sarcoma (STS) patients. We investigated the efficacy of radiation therapy (RT) in STS patients with PM. Methods and Materials: A retrospective chart review was performed on 154 patients with STS at various anatomic sites with PM, defined as tumor on ink, who underwent RT with curative intent between 1970 and 2001. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated by univariate (log-rank) and multivariate analysis of prognostic and treatment factors. Results: At 5 years, actuarial LC, DFS, and OS rates were: 76%, 46.7%, and 65.2%, respectively. LC was highest with extremity lesions (p < 0.01), radiation dose >64 Gy (p < 0.05), microscopically (vs. grossly visible) positive margin (p = 0.03), and superficial lesions (p = 0.05). Patients receiving >64 Gy had higher 5-year LC, DFS, and OS rates of 85%, 52.1%, and 67.8% vs. 66.1%, 41.8%, and 62.9% if {<=}64 Gy, p < 0.04. OS was worse in patients with G2/G3 tumors with local failure (LF), p < 0.001. Other known prognostic factors, including grade, stage, size, and age (>50), also significantly influenced OS. By multivariate analysis, the best predictors of LC were site (extremity vs. other), p < 0.01 and dose (>64 vs. {<=}64 Gy), p < 0.05; the best predictors for OS were size, p < 0.001, gross vs. microscopic PM, p < 0.05, and LF, p < 0.01. Conclusion: Local control is achieved in most PM STS patients undergoing RT. Doses >64 Gy, superficial location, and extremity site are associated with improved LC. OS is worse in patients with tumors with lesions >5 cm, grossly positive margins, and after local failure.

  3. Cyp1a reporter zebrafish reveals target tissues for dioxin.

    PubMed

    Kim, Kun-Hee; Park, Hye-Jeong; Kim, Jin Hee; Kim, Suhyun; Williams, Darren R; Kim, Myeong-Kyu; Jung, Young Do; Teraoka, Hiroki; Park, Hae-Chul; Choy, Hyon E; Shin, Boo Ahn; Choi, Seok-Yong

    2013-06-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the unintentional byproduct of various industrial processes, is classified as human carcinogen and could disrupt reproductive, developmental and endocrine systems. Induction of cyp1a1 is used as an indicator of TCDD exposure. We sought to determine tissues that are vulnerable to TCDD toxicity using a transgenic zebrafish (Danio rerio) model. We inserted a nuclear enhanced green fluorescent protein gene (EGFP) into the start codon of a zebrafish cyp1a gene in a fosmid clone using DNA recombineering. The resulting recombineered fosmid was then used to generate cyp1a reporter zebrafish, embryos of which were exposed to TCDD. Expression pattern of EGFP in the reporter zebrafish mirrored that of endogenous cyp1a mRNA. In addition, exposure of the embryos to TCDD at as low as 10 pM for 72 h, which does not elicit morphological abnormalities of embryos, markedly increased GFP expression. Furthermore, the reporter embryos responded to other AhR ligands as well. Exposure of the embryos to TCDD revealed previously reported (the cardiovascular system, liver, pancreas, kidney, swim bladder and skin) and unreported target tissues (retinal bipolar cells, otic vesicle, lateral line, cloaca and pectoral fin bud) for TCDD. Transgenic cyp1a reporter zebrafish we have developed can further understanding of ecotoxicological relevance and human health risks by TCDD. In addition, they could be used to identify agonists of AhR and antidotes to TCDD toxicity.

  4. Best immunohistochemical panel in distinguishing adenocarcinoma from squamous cell carcinoma of lung: tissue microarray assay in resected lung cancer specimens.

    PubMed

    Kim, Mi Jin; Shin, Hyeong Chan; Shin, Kyeong Cheol; Ro, Jae Y

    2013-02-01

    The emergence of the targeted therapies for non-small cell lung carcinoma (NSCLC) has generated a need for accurate histologic subtyping of NSCLC. In this study, we assessed the utility of immunohistochemical markers that could be helpful in distinction between adenocarcinoma (ADC) and squamous cell carcinoma (SCC). We performed a battery of immunohistochemistry using tissue microarray for napsin-A, Thyroid transcription factor 1 (TTF-1), p63, cytokeratin (CK) 5/6, thrombomodulin (CD141), Epithelial-related antigen (MOC-31), carcinoembryonic antigen (CEA), Cyclooxygenase 2 (COX-2), high-molecular-weight CK (HMWCK), p27kip1 (p27), and Rb protein in 129 resected primary NSCLC with 81 ADCs and 48 SCCs and 10 metastatic ADC to the lung (primary in colon, 7 cases; stomach, 2 cases; vagina, 1 case). Cases of ADC and SCC were morphologically unequivocal and solid tumors with no definite squamous or glandular differentiation were excluded for this analysis. Napsin-A and TTF-1 were positive in 81% and 70% of ADC and in 0% and 2% of SCC, respectively, whereas P63 and CK5/6 were positive in 91% and 90% of SCC and in 9% and 4% of ADC, respectively (P < .001). CD141 stained significantly higher in SCC over ADC (positive in 2% of ADC and 46% of SCC. MOC-31, CEA, COX-2, HMWCK, p27, and Rb appeared to be not useful markers in distinction between ADC and SCC because of their low specificity. None of metastatic ADC to the lung showed positive for napsin-A and TTF-1. It was evident that combination of napsin-A, TTF-1, CK5/6, and p63 was the best immunohistochemical panel in differentiating ADC from SCC of the lung in this study. CD141 appeared to be a potential new marker for SCC with high specificity. Cyclooxygenase 2, MOC-31, CEA, HMWCK, p27, and Rb showed less specificity for differentiation ADC from SCC.

  5. Laparoscopic partial splenic resection.

    PubMed

    Uranüs, S; Pfeifer, J; Schauer, C; Kronberger, L; Rabl, H; Ranftl, G; Hauser, H; Bahadori, K

    1995-04-01

    Twenty domestic pigs with an average weight of 30 kg were subjected to laparoscopic partial splenic resection with the aim of determining the feasibility, reliability, and safety of this procedure. Unlike the human spleen, the pig spleen is perpendicular to the body's long axis, and it is long and slender. The parenchyma was severed through the middle third, where the organ is thickest. An 18-mm trocar with a 60-mm Endopath linear cutter was used for the resection. The tissue was removed with a 33-mm trocar. The operation was successfully concluded in all animals. No capsule tears occurred as a result of applying the stapler. Optimal hemostasis was achieved on the resected edges in all animals. Although these findings cannot be extended to human surgery without reservations, we suggest that diagnostic partial resection and minor cyst resections are ideal initial indications for this minimally invasive approach.

  6. Tumour suppressor gene (CDKNA2) status on chromosome 9p in resected renal tissue improves prognosis of localised kidney cancer

    PubMed Central

    El-Mokadem, Ismail; Kidd, Thomas; Pratt, Norman; Fleming, Stewart; Nabi, Ghulam

    2016-01-01

    December 2005. Five microsatellite markers (D9S916, D9S1814, D9S974, D9S942 and D9S171) assessed loss of heterogeneity (LOH) using DNA samples and in the same cohort FISH analysis was accomplished on tissue microarray slides. The FISH data were scored by two observers blinded to the histological data of the patients. Cytogenetic aberrations were correlated with histological and clinical outcomes by univariate and multivariate analyses using different prognostic models. Disease specific and recurrence free survival based on cytogenetic changes were assessed by Kaplan Meier methods. Conclusions A comprehensive cytogenetic analysis using microsatellite analysis and FISH of the CDKN2A region on chromosome 9p improves the predictive accuracy of known prognostic factors in clinically localised renal cell carcinoma undergoing surgical resection. PMID:27682877

  7. Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer*

    PubMed Central

    Chen, Chien-Lun; Chung, Ting; Wu, Chih-Ching; Ng, Kwai-Fong; Yu, Jau-Song; Tsai, Cheng-Han; Chang, Yu-Sun; Liang, Ying; Tsui, Ke-Hung; Chen, Yi-Ting

    2015-01-01

    More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for ∼150,200 deaths each year. To discover potential biomarkers of bladder cancer, we employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens. Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for use in two batches of isobaric tags for relative and absolute quantitation experiments, which identified a total of 3220 proteins. A DAVID (database for annotation, visualization and integrated discovery) analysis of dysregulated proteins revealed that the three top-ranking biological processes were extracellular matrix organization, extracellular structure organization, and oxidation-reduction. Biological processes including response to organic substances, response to metal ions, and response to inorganic substances were highlighted by up-expressed proteins in bladder cancer. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins—SLC3A2, STMN1, and TAGLN2—in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC = 0.999) and evaluating lymph node metastasis in bladder cancer patients. ELISA results revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. In comparisons with age-matched hernia urine specimens, urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an area-under-the-curve value of 0.70 (p < 0.001, n = 205). Overall, TAGLN2 showed the most significant

  8. Treatment of a chronic vesicocutaneous fistula and abdominal wall defect after resection of a soft tissue sarcoma using a bipedicled latissimus dorsi and serratus anterior free flap.

    PubMed

    Ludolph, Ingo; Apel, Hendrik; Horch, Raymund E; Beier, Justus P

    2014-11-01

    We present a surgical treatment for bladder reconstruction in a case of chronic vesicocutaneous radiation-induced fistula and reconstruction of the abdominal wall after resection of a liposarcoma in the rectus abdominis muscle. Fistulas are sequelae after radiotherapy. To regain bladder function and reconstitute abdominal wall stability, a microsurgical flap approach should be considered. A male patient underwent resection of a liposarcoma in the rectus abdominis muscle with adjuvant radiotherapy, suffering from a chronic vesicocutaneous fistula. A bipedicled combined latissimus dorsi and serratus anterior flap was carried out after resection of the fistula for reconstruction of the urine bladder and the abdominal wall. Ascending urethrography 4 weeks postoperatively showed no leakage. In the 4-month follow-up period, no signs of recurrence of the fistula or herniation occurred. A bipedicled flap allowed reconstruction of the urine bladder and the abdominal wall. Using non-irradiated, well-perfused intra-abdominal muscle tissue over the urine bladder prevented recurrence of the fistula.

  9. Functional Tissue Analysis Reveals Successful Cryopreservation of Human Osteoarthritic Synovium

    PubMed Central

    de Vries, Marieke; Bennink, Miranda B.; van Lent, Peter L. E. M.; van der Kraan, Peter M.; Koenders, Marije I.; Thurlings, Rogier M.; van de Loo, Fons A. J.

    2016-01-01

    Osteoarthritis (OA) is a degenerative joint disease affecting cartilage and is the most common form of arthritis worldwide. One third of OA patients have severe synovitis and less than 10% have no evidence of synovitis. Moreover, synovitis is predictive for more severe disease progression. This offers a target for therapy but more research on the pathophysiological processes in the synovial tissue of these patients is needed. Functional studies performed with synovial tissue will be more approachable when this material, that becomes available by joint replacement surgery, can be stored for later use. We set out to determine the consequences of slow-freezing of human OA synovial tissue. Therefore, we validated a method that can be applied in every routine laboratory and performed a comparative study of five cryoprotective agent (CPA) solutions. To determine possible deleterious cryopreservation-thaw effects on viability, the synovial tissue architecture, metabolic activity, RNA quality, expression of cryopreservation associated stress genes, and expression of OA characteristic disease genes was studied. Furthermore, the biological activity of the cryopreserved tissue was determined by measuring cytokine secretion induced by the TLR ligands lipopolysaccharides and Pam3Cys. Compared to non frozen synovium, no difference in cell and tissue morphology could be identified in the conditions using the CS10, standard and CryoSFM CPA solution for cryopreservation. However, we observed significantly lower preservation of tissue morphology with the Biofreeze and CS2 media. The other viability assays showed trends in the same direction but were not sensitive enough to detect significant differences between conditions. In all assays tested a clearly lower viability was detected in the condition in which synovium was frozen without CPA solution. This detailed analysis showed that OA synovial tissue explants can be cryopreserved while maintaining the morphology, viability and

  10. Metastasis Initiating Cells in Primary Prostate Cancer Tissues From Transurethral Resection of the Prostate (TURP) Predicts Castration-Resistant Progression and Survival of Prostate Cancer Patients

    PubMed Central

    Li, Qinlong; Li, Quanlin; Nuccio, Jill; Liu, Chunyan; Duan, Peng; Wang, Ruoxiang; Jones, Lawrence W.; Chung, Leland W. K.; Zhau, Haiyen E.

    2016-01-01

    BACKGROUND We previouslyreported that the activation of RANK and c-Met signaling components in both experimental mouse models and human prostate cancer (PC) specimens predicts bone metastatic potential and PC patient survival. This study addresses whether a population of metastasis-initiating cells (MICs) known to express a stronger RANKL, phosphorylated c-Met (p-c-Met), and neuropilin-1 (NRP1) signaling network than bystander or dormant cells (BDCs) can be detected in PC tissues from patients subjected to transurethral resection of the prostate (TURP) for urinary obstruction prior to the diagnosis of PC with or without prior hormonal manipulation, and whether the relative abundance of MICs over BDCs could predict castration-resistant progression and PC patient survival. METHODS We employed a multiplexed quantum-dot labeling (mQDL) protocol to detect and quantify MICs and BDCs at the single cell level in TURP tissues obtained from 44 PC patients with documented overall survival and castration resistance status. RESULTS PC tissues with a higher number of MICs and an activated RANK signaling network, including increased expression of RANKL, p-c-Met, and NRP1 compared to BDCs, were found to correlate with the development of castration resistance and overall survival. CONCLUSIONS The assessment of PC cells with MIC and BDC phenotypes in primary PC tissues from hormone-naïve patients can predict the progression to castration resistance and the overall survival of PC patients. PMID:25990623

  11. [Hepatic resections].

    PubMed

    Mercado, M A; Paquet, K J

    1990-07-01

    Liver resection are now accepted as a part of the surgical therapeutic armamentarium. In this review the anatomical and technical aspects, as well as the main indications, are discussed. The new image technique have largely contributed to the early detection of lesions that can be resected. The main indication for these procedures are malignant lesions (primary or metastatic) as well as symptomatic benign lesions. The importance to study, diagnose and treat benign lesions are justified by the possibility to detect and resect a potentially curable malignant disease. Major liver resections are contraindicated in patients with liver cirrhosis, because of a high morbimortality. Operative mortality for major liver resection is about 10% in most centers and the survival of patients with malignant disease treated by this modality is better than that of the patients treated with conservative measures. All patients with space-occupying lesions of the liver deserve the benefit of the doubt to be considered for surgical treatment. The individual features of each patient, with a judicious balance between risk and benefit, indicate or contraindicate these procedures.

  12. Large bowel resection

    MedlinePlus

    ... colectomy; Right hemicolectomy; Left hemicolectomy; Hand assisted bowel surgery; Low anterior resection; Sigmoid colectomy; Subtotal colectomy; Proctocolectomy; Colon resection; Laparoscopic colectomy; Colectomy - partial; Abdominal perineal resection

  13. [Current Trends in Radiotherapy Following Surgical Resection of Soft-tissue Sarcoma of the Extremities and Trunk].

    PubMed

    Kraus-Tiefenbacher, U S; Van Kampen, M

    2015-04-01

    Besides surgery, radiotherapy plays its well-established part in the multimodality treatment of soft-tissue sarcomas. It can be delivered before or after surgery with similar control rates. Adjuvant radiotherapy increases the local control rates as well as the overall survival in intermediate or high-grade soft-tissue sarcomas. Due to the complex and sophisticated nature of the treatment, patients should be referred to specialised centres where modern radiotherapeutic options like intensity modulated radiotherapy and image-guided radiotherapy can be offered.

  14. Prophylactic root resection and periapical grafting for anterior implant aethetics: an integration of tissue-reconstruction and tissue-preservation concepts.

    PubMed

    Kan, Joseph Y K; Rungcharassaeng, Kitichai

    2004-06-01

    The presence of active infections involving the labial bony plate of a failing maxillary anterior tooth presents a challenging situation for aesthetic implant replacement. Not only would the septic state of an abscess be detrimental for immediate implant placement and bone augmentation, but the accompanying bony destruction would also increase the likelihood and magnitude of gingival recession, making this a bioaesthetic challenge. This article describes a technique that integrates tissue-reconstruction and tissue-preservation concepts to achieve peri-implant tissue aesthetics as well as its clinical rationale.

  15. Combined surgical resective and regenerative therapy for advanced peri-implantitis with concomitant soft tissue volume augmentation: a case report.

    PubMed

    Schwarz, Frank; John, Gordon; Sahm, Narja; Becker, Jürgen

    2014-01-01

    This case report presents a 3-year follow-up of the clinical outcomes of a combined surgical therapy for advanced peri-implantitis with concomitant soft tissue volume augmentation using a collagen matrix. One patient suffering from advanced peri-implantitis and a thin mucosal biotype underwent access flap surgery, implantoplasty at buccally and supracrestally exposed implant parts, and augmentation of the intrabony components using a natural bone mineral and a native collagen membrane after surface decontamination. A collagen matrix was applied to the wound area to increase soft tissue volume and support transmucosal healing. The following clinical parameters were recorded over a period of 3 years: bleeding on probing (BOP), probing depth (PD), mucosal recession (MR), clinical attachment level (CAL), and width of keratinized mucosa (KM). At 36 months, the combined surgical procedure was associated with a clinically important reduction in mean BOP (100%), PD (4.3 ± 0.5 mm), and CAL (4.4 ± 0.4 mm). Site-level analysis of the buccal aspects pointed to an increase in MR (-1.0 ± 0.4 mm) and a decrease in KM (-1.3 ± 0.5 mm) values at 12 months. However, a regain in mucosal height and KM was noted at 24 months, even reaching respective baseline values after 36 months of healing. The presented combined surgical procedure was effective in controlling an advanced peri-implantitis lesion without compromising the overall esthetic outcome in the long term.

  16. Use of the Composite Pedicled Pectoralis Minor Flap after Resection of Soft Tissue Sarcoma in Reconstruction of the Glenohumeral Joint

    PubMed Central

    van de Sande, Michiel A. J.; Cosker, Tom; McDonnell, Stephen M.; Gibbons, C. L. M. H.; Giele, Henk

    2014-01-01

    The surgical repair of an extensive anterior glenohumeral soft tissue defect is complicated by glenohumeral instability and subsequent significant functional deficit. This surgical note offers a relatively simple reconstruction of the anterior capsule and subscapularis muscle using a pectoralis minor pedicle flap. This reconstruction is supplemented with functional reconstruction of the anterior glenohumeral joint. A conventional deltopectoral approach is utilized and pectoralis minor is freed from its coracoid insertion, released, and mobilized without compromising the pedicle entering from the dorsum and inferior one-third of the muscle. The mobilized pectoralis minor vascular pedicle has sufficient length for the pectoralis minor to be transferred to provide coverage of the anterior shoulder joint even in full external rotation, providing anterior stability. To further improve glenohumeral stability and shoulder function, the pectoralis major muscle can be split with the clavicular part reinserted lateral to the bicipital groove onto the lesser tuberosity replacing subscapularis function while stabilising the glenohumeral joint. PMID:25610683

  17. A Balanced Tissue Composition Reveals New Metabolic and Gene Expression Markers in Prostate Cancer

    PubMed Central

    Tessem, May-Britt; Bertilsson, Helena; Angelsen, Anders; Bathen, Tone F.; Drabløs, Finn; Rye, Morten Beck

    2016-01-01

    Molecular analysis of patient tissue samples is essential to characterize the in vivo variability in human cancers which are not accessible in cell-lines or animal models. This applies particularly to studies of tumor metabolism. The challenge is, however, the complex mixture of various tissue types within each sample, such as benign epithelium, stroma and cancer tissue, which can introduce systematic biases when cancers are compared to normal samples. In this study we apply a simple strategy to remove such biases using sample selections where the average content of stroma tissue is balanced between the sample groups. The strategy is applied to a prostate cancer patient cohort where data from MR spectroscopy and gene expression have been collected from and integrated on the exact same tissue samples. We reveal in vivo changes in cancer-relevant metabolic pathways which are otherwise hidden in the data due to tissue confounding. In particular, lowered levels of putrescine are connected to increased expression of SRM, reduced levels of citrate are attributed to upregulation of genes promoting fatty acid synthesis, and increased succinate levels coincide with reduced expression of SUCLA2 and SDHD. In addition, the strategy also highlights important metabolic differences between the stroma, epithelium and prostate cancer. These results show that important in vivo metabolic features of cancer can be revealed from patient data only if the heterogeneous tissue composition is properly accounted for in the analysis. PMID:27100877

  18. Metabolomics Reveals the Heterogeneous Secretome of Two Entomopathogenic Fungi to Ex Vivo Cultured Insect Tissues

    PubMed Central

    de Bekker, Charissa; Smith, Philip B.; Patterson, Andrew D.; Hughes, David P.

    2013-01-01

    Fungal entomopathogens rely on cellular heterogeneity during the different stages of insect host infection. Their pathogenicity is exhibited through the secretion of secondary metabolites, which implies that the infection life history of this group of environmentally important fungi can be revealed using metabolomics. Here metabolomic analysis in combination with ex vivo insect tissue culturing shows that two generalist isolates of the genus Metarhizium and Beauveria, commonly used as biological pesticides, employ significantly different arrays of secondary metabolites during infectious and saprophytic growth. It also reveals that both fungi exhibit tissue specific strategies by a distinguishable metabolite secretion on the insect tissues tested in this study. In addition to showing the important heterogeneous nature of these two entomopathogens, this study also resulted in the discovery of several novel destruxins and beauverolides that have not been described before, most likely because previous surveys did not use insect tissues as a culturing system. While Beauveria secreted these cyclic depsipeptides when encountering live insect tissues, Metarhizium employed them primarily on dead tissue. This implies that, while these fungi employ comparable strategies when it comes to entomopathogenesis, there are most certainly significant differences at the molecular level that deserve to be studied. PMID:23940603

  19. Robotic resection of an aortic valve papillary fibroelastoma.

    PubMed

    Woo, Y Joseph; Grand, Todd J; Weiss, Stuart J

    2005-09-01

    Robotic technology has been applied to multiple cardiac surgical procedures. Purported benefits include decreased tissue trauma, reduced postoperative bleeding, fewer blood product transfusions, and shorter lengths of stay. We describe the case of a 50-year-old man with an incidentally discovered 1-cm mobile mass on the edge of the aortic valve noncoronary leaflet. The patient underwent robotic minimally invasive resection. The pathologic examination revealed papillary fibroelastoma.

  20. Comprehensive Tissue-Specific Transcriptome Analysis Reveals Distinct Regulatory Programs during Early Tomato Fruit Development.

    PubMed

    Pattison, Richard J; Csukasi, Fabiana; Zheng, Yi; Fei, Zhangjun; van der Knaap, Esther; Catalá, Carmen

    2015-08-01

    Fruit formation and early development involve a range of physiological and morphological transformations of the various constituent tissues of the ovary. These developmental changes vary considerably according to tissue type, but molecular analyses at an organ-wide level inevitably obscure many tissue-specific phenomena. We used laser-capture microdissection coupled to high-throughput RNA sequencing to analyze the transcriptome of ovaries and fruit tissues of the wild tomato species Solanum pimpinellifolium. This laser-capture microdissection-high-throughput RNA sequencing approach allowed quantitative global profiling of gene expression at previously unobtainable levels of spatial resolution, revealing numerous contrasting transcriptome profiles and uncovering rare and cell type-specific transcripts. Coexpressed gene clusters linked specific tissues and stages to major transcriptional changes underlying the ovary-to-fruit transition and provided evidence of regulatory modules related to cell division, photosynthesis, and auxin transport in internal fruit tissues, together with parallel specialization of the pericarp transcriptome in stress responses and secondary metabolism. Analysis of transcription factor expression and regulatory motifs indicated putative gene regulatory modules that may regulate the development of different tissues and hormonal processes. Major alterations in the expression of hormone metabolic and signaling components illustrate the complex hormonal control underpinning fruit formation, with intricate spatiotemporal variations suggesting separate regulatory programs.

  1. Perspectives of holmium laser resection of the prostate: cutting effects with the holmium:YAG laser

    NASA Astrophysics Data System (ADS)

    Eichenauer, Rolf H.; Droege, Gerit; Brinkmann, Ralf; Neuss, Malte; Gafumbegete, Evariste; Jocham, Dieter

    1998-07-01

    Laser prostatectomy shows an improvement in peak urinary flow rates, in post-void residual urine volumes and also a symptomatic improvement when compared to the transurethral resection of the prostate (TUR-P). Time to achieve symptomatic improvement is delayed with many established laser procedures compared to standard resection. However, this disadvantage can be solved with a new resection technique using a pulsed holmium laser. Nevertheless, this advanced technique shows a few problems in a first clinical trial. Besides this clinical study, in vitro experiments were carried out in order to determine the optimal irradiation parameters with respect to resection rate, incision/ablation quality and handling. Prostate tissue of radical prostatectomies and chicken breast as model were irradiated with a pulsed holmium-laser in vitro with different laser parameters using a bare fiber in contact to tissue. The incision quality (depths and coagulation/vaporization effects) was analyzed with regard to pulse energy (speed of incision, angle of incision) and fiber diameter. Fast flash photography was performed to analyze thermo-mechanical side-effects. Fast flash photography reveals cavitation bubble up to 7 mm length in water and dissections in tissue. The ablation rate increases proportional to the laser pulse energy. The Holmium Laser Resection of the Prostate (HOLRP) in humans with available instrumentation right now shows equieffective results compared to the transurethral resection, no need for transfusion, no transurethral resection syndrome, short time for catheterization. Further technical approvement may significantly improve holmium laser prostate resection. We present a new application system for the laser resection.

  2. Human Lung Tissue Explants Reveal Novel Interactions during Legionella pneumophila Infections

    PubMed Central

    Jäger, Jens; Marwitz, Sebastian; Tiefenau, Jana; Rasch, Janine; Shevchuk, Olga; Kugler, Christian

    2014-01-01

    Histological and clinical investigations describe late stages of Legionnaires' disease but cannot characterize early events of human infection. Cellular or rodent infection models lack the complexity of tissue or have nonhuman backgrounds. Therefore, we developed and applied a novel model for Legionella pneumophila infection comprising living human lung tissue. We stimulated lung explants with L. pneumophila strains and outer membrane vesicles (OMVs) to analyze tissue damage, bacterial replication, and localization as well as the transcriptional response of infected tissue. Interestingly, we found that extracellular adhesion of L. pneumophila to the entire alveolar lining precedes bacterial invasion and replication in recruited macrophages. In contrast, OMVs predominantly bound to alveolar macrophages. Specific damage to septa and epithelia increased over 48 h and was stronger in wild-type-infected and OMV-treated samples than in samples infected with the replication-deficient, type IVB secretion-deficient DotA− strain. Transcriptome analysis of lung tissue explants revealed a differential regulation of 2,499 genes after infection. The transcriptional response included the upregulation of uteroglobin and the downregulation of the macrophage receptor with collagenous structure (MARCO). Immunohistochemistry confirmed the downregulation of MARCO at sites of pathogen-induced tissue destruction. Neither host factor has ever been described in the context of L. pneumophila infections. This work demonstrates that the tissue explant model reproduces realistic features of Legionnaires' disease and reveals new functions for bacterial OMVs during infection. Our model allows us to characterize early steps of human infection which otherwise are not feasible for investigations. PMID:24166955

  3. Quantitative proteomics by SWATH-MS reveals sophisticated metabolic reprogramming in hepatocellular carcinoma tissues

    PubMed Central

    Gao, Yanyan; Wang, Xinzheng; Sang, Zhihong; Li, Zongcheng; Liu, Feng; Mao, Jie; Yan, Dan; Zhao, Yongqiang; Wang, Hongli; Li, Ping; Ying, Xiaomin; Zhang, Xuemin; He, Kun; Wang, Hongxia

    2017-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and understanding its molecular pathogenesis is pivotal to managing this disease. Sequential window acquisition of all theoretical mass spectra (SWATH-MS) is an optimal proteomic strategy to seek crucial proteins involved in HCC development and progression. In this study, a quantitative proteomic study of tumour and adjacent non-tumour liver tissues was performed using a SWATH-MS strategy. In total, 4,216 proteins were reliably quantified, and 338 were differentially expressed, with 191 proteins up-regulated and 147 down-regulated in HCC tissues compared with adjacent non-tumourous tissues. Functional analysis revealed distinct pathway enrichment of up- and down-regulated proteins. The most significantly down-regulated proteins were involved in metabolic pathways. Notably, our study revealed sophisticated metabolic reprogramming in HCC, including alteration of the pentose phosphate pathway; serine, glycine and sarcosine biosynthesis/metabolism; glycolysis; gluconeogenesis; fatty acid biosynthesis; and fatty acid β-oxidation. Twenty-seven metabolic enzymes, including PCK2, PDH and G6PD, were significantly changed in this study. To our knowledge, this study presents the most complete view of tissue-specific metabolic reprogramming in HCC, identifying hundreds of differentially expressed proteins, which together form a rich resource for novel drug targets or diagnostic biomarker discovery. PMID:28378759

  4. Quantitative proteomics by SWATH-MS reveals sophisticated metabolic reprogramming in hepatocellular carcinoma tissues.

    PubMed

    Gao, Yanyan; Wang, Xinzheng; Sang, Zhihong; Li, Zongcheng; Liu, Feng; Mao, Jie; Yan, Dan; Zhao, Yongqiang; Wang, Hongli; Li, Ping; Ying, Xiaomin; Zhang, Xuemin; He, Kun; Wang, Hongxia

    2017-04-05

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and understanding its molecular pathogenesis is pivotal to managing this disease. Sequential window acquisition of all theoretical mass spectra (SWATH-MS) is an optimal proteomic strategy to seek crucial proteins involved in HCC development and progression. In this study, a quantitative proteomic study of tumour and adjacent non-tumour liver tissues was performed using a SWATH-MS strategy. In total, 4,216 proteins were reliably quantified, and 338 were differentially expressed, with 191 proteins up-regulated and 147 down-regulated in HCC tissues compared with adjacent non-tumourous tissues. Functional analysis revealed distinct pathway enrichment of up- and down-regulated proteins. The most significantly down-regulated proteins were involved in metabolic pathways. Notably, our study revealed sophisticated metabolic reprogramming in HCC, including alteration of the pentose phosphate pathway; serine, glycine and sarcosine biosynthesis/metabolism; glycolysis; gluconeogenesis; fatty acid biosynthesis; and fatty acid β-oxidation. Twenty-seven metabolic enzymes, including PCK2, PDH and G6PD, were significantly changed in this study. To our knowledge, this study presents the most complete view of tissue-specific metabolic reprogramming in HCC, identifying hundreds of differentially expressed proteins, which together form a rich resource for novel drug targets or diagnostic biomarker discovery.

  5. Prognostic Value of External Beam Radiation Therapy in Patients Treated With Surgical Resection and Intraoperative Electron Beam Radiation Therapy for Locally Recurrent Soft Tissue Sarcoma: A Multicentric Long-Term Outcome Analysis

    SciTech Connect

    Calvo, Felipe A.; Sole, Claudio V.; Cambeiro, Mauricio; Montero, Angel; Polo, Alfredo; Gonzalez, Carmen; Cuervo, Miguel; San Julian, Mikel; and others

    2014-01-01

    Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy.

  6. Advantages and Limitations of Direct PCR Amplification of Bacterial 16S-rDNA from Resected Heart Tissue or Swabs Followed by Direct Sequencing for Diagnosing Infective Endocarditis: A Retrospective Analysis in the Routine Clinical Setting

    PubMed Central

    Maneg, Daniela; Sponsel, Janina; Müller, Iris; Lohr, Benedikt; Penders, John; Madlener, Katharina; Hunfeld, Klaus-Peter

    2016-01-01

    Infective endocarditis (IE) is a life-threatening disease that is associated with high morbidity and mortality. Its long-term prognosis strongly depends on a timely and optimized antibiotic treatment. Therefore, identification of the causative pathogen is crucial and currently based on blood cultures followed by characterization and susceptibility testing of the isolate. However, antibiotic treatment starting prior to blood sampling or IE caused by fastidious or intracellular microorganisms may cause negative culture results. Here we investigate the additional diagnostic value of broad-range PCR in combination with direct sequencing on resected heart tissue or swabs in patients with tissue or swab culture-negative IE in a routine clinical setting. Sensitivity, specificity, and positive and negative predictive values of broad-range PCR from diagnostic material in our patients were 33.3%, 76.9%, 90.9%, and 14.3%, respectively. We identified a total of 20 patients (21.5%) with tissue or culture-negative IE who profited by the additional application of broad-range PCR. We conclude that broad-range PCR on resected heart tissue or swabs is an important complementary diagnostic approach. It should be seen as an indispensable new tool for both the therapeutic and diagnostic management of culture-negative IE and we thus propose its possible inclusion in Duke's diagnostic classification scheme. PMID:27110570

  7. Transgenic Zebrafish Reveal Tissue-Specific Differences in Estrogen Signaling in Response to Environmental Water Samples

    PubMed Central

    Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki S.; Halpern, Marnie E.

    2014-01-01

    Background: Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. Results: We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ERα was expressed in developing heart valves but not in the liver, whereas ERβ2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves. Citation: Gorelick DA, Iwanowicz LR, Hung AL, Blazer VS, Halpern ME. 2014. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to

  8. Regeneration of a Tooth in a Tissue-Engineered Mandible After Resection of a Central Giant Cell Tumor. Demonstrating Evidence of Functional Matrix Theory and Ectodermal Origin of Teeth in a Human Model-A Case Report.

    PubMed

    Melville, James C; Couey, Marcus A; Tong, Matthew S; Marx, Robert E

    2016-09-29

    Central giant cell tumors (CGCTs) are uncommon lesions occurring in the jaw. They are benign but locally destructive osteolytic lesions. They usually occur in pediatric patients 5 to 15 years of age. Multiple noninvasive modalities of treatment (intralesional steroids, interferon, calcitonin, and denosumab) have been described for those lesions, but for those that are refractory to treatment, enucleation and curettage or resection is a curative surgery. This case report describes a pediatric patient who was diagnosed with an aggressive CGCT of the left mandible encompassing the right angle to the condyle. The lesion became refractory to noninvasive treatments and immediate resection and reconstruction was performed using principles of tissue engineering. After 5 years of close observation, the patient showed normal morphology and growth of his mandible, but surprisingly developed a left mandibular third molar (tooth 17) in the site of the mandibular resection and reconstruction. This is the first case report in the literature to show the spontaneous development of teeth in a human reconstructed mandible, contributing evidence toward the functional matrix theory of mandibular growth and ectodermal origin of teeth.

  9. Super-resolution microscopy reveals altered desmosomal protein organization in pemphigus vulgaris patient tissue

    PubMed Central

    Stahley, Sara N.; Warren, Maxine F.; Feldman, Ron J.; Swerlick, Robert A.; Mattheyses, Alexa L.; Kowalczyk, Andrew P.

    2015-01-01

    Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease in which autoantibodies (IgG) are directed against the desmosomal cadherin desmoglein 3 (Dsg3). In order to better understand how PV IgG alters desmosome morphology and function in vivo, PV patient biopsies were analyzed by structured illumination microscopy (SIM), a form of super-resolution fluorescence microscopy. In patient tissue, desmosomal proteins were aberrantly clustered and localized to PV IgG-containing endocytic linear arrays. Patient IgG also colocalized with markers for lipid rafts and endosomes. Additionally, steady-state levels of Dsg3 were decreased and desmosomes were reduced in size in patient tissue. Desmosomes at blister sites were occasionally split, with PV IgG decorating the extracellular faces of split desmosomes. Desmosome splitting was recapitulated in vitro by exposing cultured keratinocytes both to PV IgG and to mechanical stress, demonstrating that splitting at the blister interface in patient tissue is due to compromised desmosomal adhesive function. These findings indicate that Dsg3 clustering and endocytosis are associated with reduced desmosome size and adhesion defects in PV patient tissue. Further, this study reveals that super-resolution optical imaging is powerful approach for studying epidermal adhesion structures in normal and diseased skin. PMID:26763424

  10. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin.

    PubMed

    Hoadley, Katherine A; Yau, Christina; Wolf, Denise M; Cherniack, Andrew D; Tamborero, David; Ng, Sam; Leiserson, Max D M; Niu, Beifang; McLellan, Michael D; Uzunangelov, Vladislav; Zhang, Jiashan; Kandoth, Cyriac; Akbani, Rehan; Shen, Hui; Omberg, Larsson; Chu, Andy; Margolin, Adam A; Van't Veer, Laura J; Lopez-Bigas, Nuria; Laird, Peter W; Raphael, Benjamin J; Ding, Li; Robertson, A Gordon; Byers, Lauren A; Mills, Gordon B; Weinstein, John N; Van Waes, Carter; Chen, Zhong; Collisson, Eric A; Benz, Christopher C; Perou, Charles M; Stuart, Joshua M

    2014-08-14

    Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.

  11. Super-Resolution Microscopy Reveals Altered Desmosomal Protein Organization in Tissue from Patients with Pemphigus Vulgaris.

    PubMed

    Stahley, Sara N; Warren, Maxine F; Feldman, Ron J; Swerlick, Robert A; Mattheyses, Alexa L; Kowalczyk, Andrew P

    2016-01-01

    Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease in which autoantibodies (IgG) are directed against the desmosomal cadherin desmoglein 3. To better understand how PV IgG alters desmosome morphology and function in vivo, biopsies from patients with PV were analyzed by structured illumination microscopy, a form of superresolution fluorescence microscopy. In patient tissue, desmosomal proteins were aberrantly clustered and patient IgG colocalized with markers for lipid rafts and endosomes. Additionally, steady-state levels of desmoglein 3 were decreased and desmosomes were reduced in size in patient tissue. Desmosomes at blister sites were occasionally split, with PV IgG decorating the extracellular faces of split desmosomes. Desmosome splitting was recapitulated in vitro by exposing cultured keratinocytes both to PV IgG and to mechanical stress, demonstrating that splitting at the blister interface in patient tissue is due to compromised desmosomal adhesive function. These findings indicate that desmoglein 3 clustering and endocytosis are associated with reduced desmosome size and adhesion defects in tissue of patients with PV. Further, this study reveals that superresolution optical imaging is a powerful approach for studying epidermal adhesion structures in normal and diseased skin.

  12. Proteomics Analysis of Ovarian Cancer Cell Lines and Tissues Reveals Drug Resistance-associated Proteins

    PubMed Central

    CRUZ*, ISA N.; COLEY*, HELEN M.; KRAMER, HOLGER B.; MADHURI, THUMULURU KAVITAH; SAFUWAN, NUR A.M.; ANGELINO, ANA RITA; YANG, MIN

    2016-01-01

    Background: Carboplatin and paclitaxel form the cornerstone of chemotherapy for epithelial ovarian cancer, however, drug resistance to these agents continues to present challenges. Despite extensive research, the mechanisms underlying this resistance remain unclear. Materials and Methods: A 2D-gel proteomics method was used to analyze protein expression levels of three human ovarian cancer cell lines and five biopsy samples. Representative proteins identified were validated via western immunoblotting. Ingenuity pathway analysis revealed metabolomic pathway changes. Results: A total of 189 proteins were identified with restricted criteria. Combined treatment targeting the proteasome-ubiquitin pathway resulted in re-sensitisation of drug-resistant cells. In addition, examination of five surgical biopsies of ovarian tissues revealed α-enolase (ENOA), elongation factor Tu, mitochondrial (EFTU), glyceraldehyde-3-phosphate dehydrogenase (G3P), stress-70 protein, mitochondrial (GRP75), apolipoprotein A-1 (APOA1), peroxiredoxin (PRDX2) and annexin A (ANXA) as candidate biomarkers of drug-resistant disease. Conclusion: Proteomics combined with pathway analysis provided information for an effective combined treatment approach overcoming drug resistance. Analysis of cell lines and tissues revealed potential prognostic biomarkers for ovarian cancer. *These Authors contributed equally to this study. PMID:28031236

  13. Single cell analysis reveals gametic and tissue-specific instability of the SCA1 CAG repeat

    SciTech Connect

    Chong, S.S.; McCall, A.E.; Cota, J.

    1994-09-01

    Spinocerebellar ataxia type 1 is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat within the SCA1 gene on chromosome 6p22-23. We performed a comparative analysis of the SCA1 CAG repeat from blood and sperm of an affected male. Genomic amplification revealed a broader smear of the SCA1 allele product from sperm compared to that from peripheral blood leukocytes (PBL). To resolve this observed difference, we analyzed single sperm directly and demonstrate that the SCA1 allele in PBL is also heterogeneous, although the range of variability in allele sizes is much less than that observed in sperm. Limited genome analysis was also performed on PBL DNA from an unaffected individual with an upper normal allele of 36 repeats in parallel with an affected individual with an expanded allele of 40 repeats. The 36 repeat normal allele, which contains a CAT interruption, was completely stable compared to the uninterrupted repeat of the SCA1 allele, demonstrating a direct correlation between absence of a CAT interruption and somatic instability of the repeat. We also analyzed the size of the CAG repeat in tissues derived from various brain regions from a patient with juvenile-onset disease to determine if the size of the expansion correlated with the site of neuropathology. The results clearly show tissue-specific differences in mosaicism of repeat length. More importantly, the pattern of tissue-specific differences in repeat-length mosaicism in SCA1 within the brain parallels those seen in Huntington disease. In both disorders the expanded alleles are smaller in cerebellar tissue. These results suggest that the observed tissue-specific differences in instability of the SCA1 CAG repeat, either within the brain or between blood and sperm, are a function of the intracellular milieu or the intrinsic replicative potential of the various celltypes.

  14. Resection of gastrinomas.

    PubMed Central

    Deveney, C W; Deveney, K E; Stark, D; Moss, A; Stein, S; Way, L W

    1983-01-01

    Exploratory laparotomy and a search for gastrinomas was performed in 52 patients with the Zollinger-Ellison syndrome (ZES). Gastrinoma tissue was resected in 11 patients (21%), 6 (12%) of whom appear to have been cured. After surgery, serum gastrin levels in these six patients have remained normal from 10 months to 10 years. In the 46 other patients, tumor was unresectable because of metastases or multiple primary tumors (21 patients; 40%) or inability to find the tumor at laparotomy (21 patients; 40%). Multiple pancreatic islet cell adenomata were found in six of seven patients with multiple endocrine neoplasia (MEN), indicating that patients with this condition usually have diffuse involvement of the pancreas. The results of CT scans correlated with findings at laparotomy in 13 of 16 patients. The smallest tumor detected by CT scans was 1 cm in diameter. CT technology is more accurate in finding gastrinomas now than in the past and has a useful role in preoperative evaluation. The possibility of resection should be seriously considered in every patient with Zollinger-Ellison syndrome. Abdominal CT scans, transhepatic portal venous sampling, and laparotomy should be used to find the tumor and to determine whether it is resectable. Using presently available methods, it should be possible to cure about 25% of patients with gastrinomas who do not have MEN and over 70% of those without MEN who appear to have a solitary tumor. Total pancreatectomy may be necessary to cure some patients with MEN, but that operation is rarely justified. The morbidity and mortality of surgical attempts at curing this disease have become minimal; we have had no deaths or serious complications following such operations in over 10 yrs. Total gastrectomy and indefinite use of H2-receptor blocking agents are the therapeutic options for patients with unresectable gastrinomas. Because H2-receptor blocking agents fail to control acid secretion in many patients after several yrs of therapy, total

  15. Analyses of Resected Human Brain Metastases of Breast Cancer Reveal the Association between Up-regulation of Hexokinase 2 and Poor Prognosis

    PubMed Central

    Palmieri, Diane; Fitzgerald, Daniel; Shreeve, S. Martin; Hua, Emily; Bronder, Julie L.; Weil, Robert J.; Davis, Sean; Stark, Andreas M.; Merino, Maria J.; Kurek, Raffael; Mehdorn, H. Maximilian; Davis, Gary; Steinberg, Seth M.; Meltzer, Paul S.; Aldape, Kenneth; Steeg, Patricia S.

    2009-01-01

    Brain metastases of breast cancer appear to be increasing in incidence as systemic therapy improves. Metastatic disease in the brain is associated with high morbidity and mortality. We present the first gene expression analysis of laser captured epithelial cells from resected human brain metastases of breast cancer compared to unlinked primary breast tumors. The tumors were matched for histology, TNM stage and hormone receptor status. Most differentially expressed genes were down-regulated in the brain metastases which included, surprisingly, many genes associated with metastasis. Q-PCR analysis confirmed statistically significant differences or strong trends in the expression of six genes: BMP1, PEDF, LAMγ3, SIAH, STHMN3 and TSPD2. Hexokinase 2 (HK2) was also of interest because of its increased expression in brain metastases. HK2 is important in glucose metabolism and apoptosis. In agreement with our microarray results, HK2 levels (both mRNA and protein) were elevated in a brain metastatic derivative (231-BR) of the human breast carcinoma cell line MDA-MB-231 relative to the parental cell line (231-P), in vitro. Knockdown of HK2 expression in 231-BR cells using shRNA reduced cell proliferation when cultures were maintained in glucose limiting conditions. Finally, HK2 expression was analyzed in a cohort of 123 resected brain metastases of breast cancer. High HK2 expression was significantly associated with poor patient survival post-craniotomy (P=0.028). The data suggest that HK2 overexpression is associated with metastasis to the brain in breast cancer and it may be a therapeutic target. PMID:19723875

  16. High-intensity focused ultrasound combined with hysteroscopic resection to treat retained placenta accreta

    PubMed Central

    Lee, Jae-Seong; Hong, Gi-Youn; Park, Byung-Joon; Hwang, Hyejin; Kim, Rayon

    2016-01-01

    We present a case of retained placenta accreta treated by high-intensity focused ultrasound (HIFU) ablation followed by hysteroscopic resection. The patient was diagnosed as submucosal myoma based on ultrasonography in local clinic. Pathologic examination of several pieces of tumor mass from the hysteroscopic procedure revealed necrotic chorionic villi with calcification. HIFU was performed using an ultrasound-guided HIFU tumor therapeutic system. The ultrasound machine had been used for real-time monitoring of the HIFU procedure. After HIFU treatment, no additional vaginal bleeding or complications were observed. A hysteroscopic resection was performed to remove ablated placental tissue 7 days later. No abnormal vaginal bleeding or discharge was seen after the procedure. The patient was stable postoperatively. We proposed HIFU and applied additional hysteroscopic resection for a safe and effective method for treating retained placenta accreta to prevent complications from the remaining placental tissue and to improve fertility options. PMID:27668209

  17. Laparoscopic resection of duodenal gastrointestinal stromal tumour

    PubMed Central

    Zioni, Tammy; Dizengof, Vitaliy; Kirshtein, Boris

    2017-01-01

    Only a few studies have revealed using laparoscopic technique with limited resection of gastrointestinal stromal tumour (GIST) of the duodenum. A 68-year-old man was admitted to the hospital due to upper gastrointestinal (GI) bleeding. Evaluation revealed an ulcerated, bleeding GI tumour in the second part of the duodenum. After control of bleeding during gastroduodenoscopy, he underwent a laparoscopic wedge resection of the area. During 1.5 years of follow-up, the patient is disease free, eats drinks well, and has regained weight. Surgical resection of duodenal GIST with free margins is the main treatment of this tumour. Various surgical treatment options have been reported. Laparoscopic resection of duodenal GIST is an advanced and challenging procedure requiring experience and good surgical technique. The laparoscopic limited resection of duodenal GIST is feasible and safe, reducing postoperative morbidity without compromising oncologic results. PMID:28281485

  18. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples

    USGS Publications Warehouse

    Gorelick, Daniel A.; Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki; Halpern, Marnie E.

    2014-01-01

    Background: Environmental endocrine disruptors (EED) are exogenous chemicals that mimic endogenous hormones, such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ER) in the larval heart compared to the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit similar tissue-specific effects as BPA and genistein or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of estrogen receptor genes by RNA in situ hybridization. Results: Selective patterns of ER activation were observed in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue-specificity in ER activation is due to differences in the expression of estrogen receptor subtypes. ERα is expressed in developing heart valves but not in the liver, whereas ERβ2 has the opposite profile. Accordingly, subtype-specific ER agonists activate the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish has revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero is associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

  19. Dynamic Proteomic Characteristics and Network Integration Revealing Key Proteins for Two Kernel Tissue Developments in Popcorn

    PubMed Central

    Du, Chunguang; Xiong, Wenwei; Chen, Xinjian; Deng, Fei; Ma, Zhiyan; Qiao, Dahe; Hu, Chunhui; Ren, Yangliu; Li, Yuling

    2015-01-01

    The formation and development of maize kernel is a complex dynamic physiological and biochemical process that involves the temporal and spatial expression of many proteins and the regulation of metabolic pathways. In this study, the protein profiles of the endosperm and pericarp at three important developmental stages were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with LC-MS/MS in popcorn inbred N04. Comparative quantitative proteomic analyses among developmental stages and between tissues were performed, and the protein networks were integrated. A total of 6,876 proteins were identified, of which 1,396 were nonredundant. Specific proteins and different expression patterns were observed across developmental stages and tissues. The functional annotation of the identified proteins revealed the importance of metabolic and cellular processes, and binding and catalytic activities for the development of the tissues. The whole, endosperm-specific and pericarp-specific protein networks integrated 125, 9 and 77 proteins, respectively, which were involved in 54 KEGG pathways and reflected their complex metabolic interactions. Confirmation for the iTRAQ endosperm proteins by two-dimensional gel electrophoresis showed that 44.44% proteins were commonly found. However, the concordance between mRNA level and the protein abundance varied across different proteins, stages, tissues and inbred lines, according to the gene cloning and expression analyses of four relevant proteins with important functions and different expression levels. But the result by western blot showed their same expression tendency for the four proteins as by iTRAQ. These results could provide new insights into the developmental mechanisms of endosperm and pericarp, and grain formation in maize. PMID:26587848

  20. [Wide resection of chest wall for intramuscular lipoma in serratus anterior muscle reconstructed by autologous tissue;report of a case].

    PubMed

    Mizuno, Kiyomichi; Urabe, Norikazu; Nakatsuka, Kazuhiko; Ishikawa, Kayoko; Eguchi, Masanobu

    2015-02-01

    A 60-years-old man with a right lateral chest wall mass visited our hospital. There was a mass of 50×45 mm on the 5th rib. The mild atypical cells were detected by the percutaneous needle biopsy, and the tumor was resected with the chest wall of which detect was reconstructed with fascia lata and latissimus dorsi muscle cutaneous flap. Pathological diagnosis was lipoma in the serratus anterior muscle. The postoperative course was uneventful without paradoxical respiration and surgical site infection. Since intramuscular lipoma is very rare and is reported to have a risk of recurrence, careful observation is necessary.

  1. Comparative tissue transcriptomics reveal prompt inter-organ communication in response to local bacterial kidney infection

    PubMed Central

    2011-01-01

    Background Mucosal infections elicit inflammatory responses via regulated signaling pathways. Infection outcome depends strongly on early events occurring immediately when bacteria start interacting with cells in the mucosal membrane. Hitherto reported transcription profiles on host-pathogen interactions are strongly biased towards in vitro studies. To detail the local in vivo genetic response to infection, we here profiled host gene expression in a recent experimental model that assures high spatial and temporal control of uropathogenic Escherichia coli (UPEC) infection within the kidney of a live rat. Results Transcriptional profiling of tissue biopsies from UPEC-infected kidney tissue revealed 59 differentially expressed genes 8 h post-infection. Their relevance for the infection process was supported by a Gene Ontology (GO) analysis. Early differential expression at 3 h and 5 h post-infection was of low statistical significance, which correlated to the low degree of infection. Comparative transcriptomics analysis of the 8 h data set and online available studies of early local infection and inflammation defined a core of 80 genes constituting a "General tissue response to early local bacterial infections". Among these, 25% were annotated as interferon-γ (IFN-γ) regulated. Subsequent experimental analyses confirmed a systemic increase of IFN-γ in rats with an ongoing local kidney infection, correlating to splenic, rather than renal Ifng induction and suggested this inter-organ communication to be mediated by interleukin (IL)-23. The use of comparative transcriptomics allowed expansion of the statistical data handling, whereby relevant data could also be extracted from the 5 h data set. Out of the 31 differentially expressed core genes, some represented specific 5 h responses, illustrating the value of comparative transcriptomics when studying the dynamic nature of gene regulation in response to infections. Conclusion Our hypothesis-free approach identified

  2. Endoscopic full-thickness resection: Current status

    PubMed Central

    Schmidt, Arthur; Meier, Benjamin; Caca, Karel

    2015-01-01

    Conventional endoscopic resection techniques such as endoscopic mucosal resection or endoscopic submucosal dissection are powerful tools for treatment of gastrointestinal neoplasms. However, those techniques are restricted to superficial layers of the gastrointestinal wall. Endoscopic full-thickness resection (EFTR) is an evolving technique, which is just about to enter clinical routine. It is not only a powerful tool for diagnostic tissue acquisition but also has the potential to spare surgical therapy in selected patients. This review will give an overview about current EFTR techniques and devices. PMID:26309354

  3. Gene expression profiles in granuloma tissue reveal novel diagnostic markers in sarcoidosis.

    PubMed

    Christophi, George P; Caza, Tiffany; Curtiss, Christopher; Gumber, Divya; Massa, Paul T; Landas, Steve K

    2014-06-01

    Sarcoidosis is an immune-mediated multisystem disease characterized by the formation of non-caseating granulomas. The pathogenesis of sarcoidosis is unclear, with proposed infectious or environmental antigens triggering an aberrant immune response in susceptible hosts. Multiple pro-inflammatory signaling pathways have been implicated in mediating macrophage activation and granuloma formation in sarcoidosis, including IFN-γ/STAT-1, IL-6/STAT-3, and NF-κB. It is difficult to distinguish sarcoidosis from other granulomatous diseases or assess disease severity and treatment response with histopathology alone. Therefore, development of improved diagnostic tools is imperative. Herein, we describe an efficient and reliable technique to classify granulomatous disease through selected gene expression and identify novel genes and cytokine pathways contributing to the pathogenesis of sarcoidosis. We quantified the expression of twenty selected mRNAs extracted from formalin-fixed paraffin embedded (FFPE) tissue (n = 38) of normal lung, suture granulomas, sarcoid granulomas, and fungal granulomas. Utilizing quantitative real-time RT-PCR we analyzed the expression of several genes, including IL-6, COX-2, MCP-1, IFN-γ, T-bet, IRF-1, Nox2, IL-33, and eotaxin-1 and revealed differential regulation between suture, sarcoidosis, and fungal granulomas. This is the first study demonstrating that quantification of target gene expression in FFPE tissue biopsies is a potentially effective diagnostic and research tool in sarcoidosis.

  4. African Lungfish Reveal the Evolutionary Origins of Organized Mucosal Lymphoid Tissue in Vertebrates.

    PubMed

    Tacchi, Luca; Larragoite, Erin T; Muñoz, Pilar; Amemiya, Chris T; Salinas, Irene

    2015-09-21

    One of the most remarkable innovations of the vertebrate adaptive immune system is the progressive organization of the lymphoid tissues that leads to increased efficiency of immune surveillance and cell interactions. The mucosal immune system of endotherms has evolved organized secondary mucosal lymphoid tissues (O-MALT) such as Peyer's patches, tonsils, and adenoids. Primitive semi-organized lymphoid nodules or aggregates (LAs) were found in the mucosa of anuran amphibians, suggesting that O-MALT evolved from amphibian LAs ∼250 million years ago. This study shows for the first time the presence of O-MALT in the mucosa of the African lungfish, an extant representative of the closest ancestral lineage to all tetrapods. Lungfish LAs are lymphocyte-rich structures associated with a modified covering epithelium and express all IGH genes except for IGHW2L. In response to infection, nasal LAs doubled their size and increased the expression of CD3 and IGH transcripts. Additionally, de novo organogenesis of inducible LAs resembling mammalian tertiary lymphoid structures was observed. Using deep-sequencing transcriptomes, we identified several members of the tumor necrosis factor (TNF) superfamily, and subsequent phylogenetic analyses revealed its extraordinary diversification within sarcopterygian fish. Attempts to find AICDA in lungfish transcriptomes or by RT-PCR failed, indicating the possible absence of somatic hypermutation in lungfish LAs. These findings collectively suggest that the origin of O-MALT predates the emergence of tetrapods and that TNF family members play a conserved role in the organization of vertebrate mucosal lymphoid organs.

  5. Metagenomic analysis reveals presence of Treponema denticola in a tissue biopsy of the Iceman.

    PubMed

    Maixner, Frank; Thomma, Anton; Cipollini, Giovanna; Widder, Stefanie; Rattei, Thomas; Zink, Albert

    2014-01-01

    Ancient hominoid genome studies can be regarded by definition as metagenomic analyses since they represent a mixture of both hominoid and microbial sequences in an environment. Here, we report the molecular detection of the oral spirochete Treponema denticola in ancient human tissue biopsies of the Iceman, a 5,300-year-old Copper Age natural ice mummy. Initially, the metagenomic data of the Iceman's genomic survey was screened for bacterial ribosomal RNA (rRNA) specific reads. Through ranking the reads by abundance a relatively high number of rRNA reads most similar to T. denticola was detected. Mapping of the metagenome sequences against the T. denticola genome revealed additional reads most similar to this opportunistic pathogen. The DNA damage pattern of specifically mapped reads suggests an ancient origin of these sequences. The haematogenous spread of bacteria of the oral microbiome often reported in the recent literature could already explain the presence of metagenomic reads specific for T. denticola in the Iceman's bone biopsy. We extended, however, our survey to an Iceman gingival tissue sample and a mouth swab sample and could thereby detect T. denticola and Porphyrimonas gingivalis, another important member of the human commensal oral microflora. Taken together, this study clearly underlines the opportunity to detect disease-associated microorganisms when applying metagenomics-enabled approaches on datasets of ancient human remains.

  6. Multispectral imaging reveals the tissue distribution of tetraspanins in human lymphoid organs.

    PubMed

    de Winde, Charlotte M; Zuidscherwoude, Malou; Vasaturo, Angela; van der Schaaf, Alie; Figdor, Carl G; van Spriel, Annemiek B

    2015-08-01

    Multispectral imaging is a novel microscopy technique that combines imaging with spectroscopy to obtain both quantitative expression data and tissue distribution of different cellular markers. Tetraspanins CD37 and CD53 are four-transmembrane proteins involved in cellular and humoral immune responses. However, comprehensive immunohistochemical analyses of CD37 and CD53 in human lymphoid organs have not been performed so far. We investigated CD37 and CD53 protein expression on primary human immune cell subsets in blood and in primary and secondary lymphoid organs. Both tetraspanins were prominently expressed on antigen-presenting cells, with highest expression of CD37 on B lymphocytes. Analysis of subcellular distribution showed presence of both tetraspanins on the plasma membrane and on endosomes. In addition, CD53 was also present on lysosomes. Quantitative analysis of expression and localization of CD37 and CD53 on lymphocytes within lymphoid tissues by multispectral imaging revealed high expression of both tetraspanins on CD20(+) cells in B cell follicles in human spleen and appendix. CD3(+) T cells within splenic T cell zones expressed lower levels of CD37 and CD53 compared to T cells in the red pulp of human spleen. B cells in human bone marrow highly expressed CD37, whereas the expression of CD53 was low. In conclusion, we demonstrate differential expression of CD37 and CD53 on primary human immune cells, their subcellular localization and their quantitative distribution in human lymphoid organs. This study provides a solid basis for better insight into the function of tetraspanins in the human immune response.

  7. African Lungfish Reveal the Evolutionary Origins of Organized Mucosal Lymphoid Tissue in Vertebrates

    PubMed Central

    Tacchi, Luca; Larragoite, Erin T.; Muñoz, Pilar; Amemiya, Chris T.

    2016-01-01

    SUMMARY One of the most remarkable innovations of the vertebrate adaptive immune system is the progressive organization of the lymphoid tissues that leads to increased efficiency of immune surveillance and cell interactions. The mucosal immune system of endotherms has evolved organized secondary mucosal lymphoid tissues (O-MALT) such as Peyer’s patches, tonsils, and adenoids. Primitive semi-organized lymphoid nodules or aggregates (LAs) were found in the mucosa of anuran amphibians [1], suggesting that O-MALT evolved from amphibian LAs_250 million years ago [1–4]. This study shows for the first time the presence of O-MALT in the mucosa of the African lungfish, an extant representative of the closest ancestral lineage to all tetrapods. Lungfish LAs are lymphocyte-rich structures associated with a modified covering epithelium and express all IGH genes except for IGHW2L. In response to infection, nasal LAs doubled their size and increased the expression of CD3 and IGH transcripts. Additionally, de novo organogenesis of inducible LAs resembling mammalian tertiary lymphoid structures was observed. Using deep-sequencing transcriptomes, we identified several members of the tumor necrosis factor (TNF) superfamily, and subsequent phylogenetic analyses revealed its extraordinary diversification within sarcopterygian fish. Attempts to find AICDA in lungfish transcriptomes or by RT-PCR failed, indicating the possible absence of somatic hypermutation in lungfish LAs. These findings collectively suggest that the origin of O-MALT predates the emergence of tetrapods and that TNF family members play a conserved role in the organization of vertebrate mucosal lymphoid organs. PMID:26344090

  8. Characterization of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension From REVEAL

    PubMed Central

    Liu, Juliana; Parsons, Lori; Hassoun, Paul M.; McGoon, Michael; Badesch, David B.; Miller, Dave P.; Nicolls, Mark R.; Zamanian, Roham T.

    2010-01-01

    Background: REVEAL (the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) is the largest US cohort of patients with pulmonary arterial hypertension (PAH) confirmed by right-sided heart catheterization (RHC), providing a more comprehensive subgroup characterization than previously possible. We used REVEAL to analyze the clinical features of patients with connective tissue disease-associated PAH (CTD-APAH). Methods: All newly and previously diagnosed patients with World Health Organization (WHO) group 1 PAH meeting RHC criteria at 54 US centers were consecutively enrolled. Cross-sectional and 1-year mortality and hospitalization analyses from time of enrollment compared CTD-APAH to idiopathic disease and systemic sclerosis (SSc) to systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). Results: Compared with patients with idiopathic disease (n = 1,251), patients with CTD-APAH (n = 641) had better hemodynamics and favorable right ventricular echocardiographic findings but a higher prevalence of pericardial effusions, lower 6-min walk distance (300.5 ± 118.0 vs 329.4 ± 134.7 m, P = .01), higher B-type natriuretic peptide (BNP) levels (432.8 ± 789.1 vs 245.6 ± 427.2 pg/mL, P < .0001), and lower diffusing capacity of carbon monoxide (Dlco) (44.9% ± 18.0% vs 63.6% ± 22.1% predicted, P < .0001). One-year survival and freedom from hospitalization were lower in the CTD-APAH group (86% vs 93%, P < .0001; 67% vs 73%, P = .03). Compared with patients with SSc-APAH (n = 399), those with other CTDs (SLE, n = 110; MCTD, n = 52; RA, n = 28) had similar hemodynamics; however, patients with SSc-APAH had the highest BNP levels (552.2 ± 977.8 pg/mL), lowest Dlco (41.2% ± 16.3% predicted), and poorest 1-year survival (82% vs 94% in SLE-APAH, 88% in MCTD-APAH, and 96% in RA-APAH). Conclusions: Patients with SSc-APAH demonstrate a unique phenotype with the highest BNP levels, lowest Dlco

  9. A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.

    PubMed

    Wong, Michael Thomas; Ong, David Eng Hui; Lim, Frances Sheau Huei; Teng, Karen Wei Weng; McGovern, Naomi; Narayanan, Sriram; Ho, Wen Qi; Cerny, Daniela; Tan, Henry Kun Kiaang; Anicete, Rosslyn; Tan, Bien Keem; Lim, Tony Kiat Hon; Chan, Chung Yip; Cheow, Peng Chung; Lee, Ser Yee; Takano, Angela; Tan, Eng-Huat; Tam, John Kit Chung; Tan, Ern Yu; Chan, Jerry Kok Yen; Fink, Katja; Bertoletti, Antonio; Ginhoux, Florent; Curotto de Lafaille, Maria Alicia; Newell, Evan William

    2016-08-16

    Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body.

  10. Raman Spectroscopy Reveals New Insights into the Zonal Organization of Native and Tissue-Engineered Articular Cartilage

    PubMed Central

    2016-01-01

    Tissue architecture is intimately linked with its functions, and loss of tissue organization is often associated with pathologies. The intricate depth-dependent extracellular matrix (ECM) arrangement in articular cartilage is critical to its biomechanical functions. In this study, we developed a Raman spectroscopic imaging approach to gain new insight into the depth-dependent arrangement of native and tissue-engineered articular cartilage using bovine tissues and cells. Our results revealed previously unreported tissue complexity into at least six zones above the tidemark based on a principal component analysis and k-means clustering analysis of the distribution and orientation of the main ECM components. Correlation of nanoindentation and Raman spectroscopic data suggested that the biomechanics across the tissue depth are influenced by ECM microstructure rather than composition. Further, Raman spectroscopy together with multivariate analysis revealed changes in the collagen, glycosaminoglycan, and water distributions in tissue-engineered constructs over time. These changes were assessed using simple metrics that promise to instruct efforts toward the regeneration of a broad range of tissues with native zonal complexity and functional performance. PMID:28058277

  11. Pyrosequencing reveals the microbial communities in the Red Sea sponge Carteriospongia foliascens and their impressive shifts in abnormal tissues.

    PubMed

    Gao, Zhao-Ming; Wang, Yong; Lee, On On; Tian, Ren-Mao; Wong, Yue Him; Bougouffa, Salim; Batang, Zenon; Al-Suwailem, Abdulaziz; Lafi, Feras F; Bajic, Vladimir B; Qian, Pei-Yuan

    2014-10-01

    Abnormality and disease in sponges have been widely reported, yet how sponge-associated microbes respond correspondingly remains inconclusive. Here, individuals of the sponge Carteriospongia foliascens under abnormal status were collected from the Rabigh Bay along the Red Sea coast. Microbial communities in both healthy and abnormal sponge tissues and adjacent seawater were compared to check the influences of these abnormalities on sponge-associated microbes. In healthy tissues, we revealed low microbial diversity with less than 100 operational taxonomic units (OTUs) per sample. Cyanobacteria, affiliated mainly with the sponge-specific species "Candidatus Synechococcus spongiarum," were the dominant bacteria, followed by Bacteroidetes and Proteobacteria. Intraspecies dynamics of microbial communities in healthy tissues were observed among sponge individuals, and potential anoxygenic phototrophic bacteria were found. In comparison with healthy tissues and the adjacent seawater, abnormal tissues showed dramatic increase in microbial diversity and decrease in the abundance of sponge-specific microbial clusters. The dominated cyanobacterial species Candidatus Synechococcus spongiarum decreased and shifted to unspecific cyanobacterial clades. OTUs that showed high similarity to sequences derived from diseased corals, such as Leptolyngbya sp., were found to be abundant in abnormal tissues. Heterotrophic Planctomycetes were also specifically enriched in abnormal tissues. Overall, we revealed the microbial communities of the cyanobacteria-rich sponge, C. foliascens, and their impressive shifts under abnormality.

  12. Multimodal and Multi-tissue Measures of Connectivity Revealed by Joint Independent Component Analysis

    PubMed Central

    Ling, Josef; Caprihan, Arvind; Calhoun, Vince D.; Jung, Rex E.; Heileman, Gregory L.

    2009-01-01

    The human brain functions as an efficient system where signals arising from gray matter are transported via white matter tracts to other regions of the brain to facilitate human behavior. However, with a few exceptions, functional and structural neuroimaging data are typically optimized to maximize the quantification of signals arising from a single source. For example, functional magnetic resonance imaging (FMRI) is typically used as an index of gray matter functioning whereas diffusion tensor imaging (DTI) is typically used to determine white matter properties. While it is likely that these signals arising from different tissue sources contain complementary information, the signal processing algorithms necessary for the fusion of neuroimaging data across imaging modalities are still in a nascent stage. In the current paper we present a data-driven method for combining measures of functional connectivity arising from gray matter sources (FMRI resting state data) with different measures of white matter connectivity (DTI). Specifically, a joint independent component analysis (J-ICA) was used to combine these measures of functional connectivity following intensive signal processing and feature extraction within each of the individual modalities. Our results indicate that one of the most predominantly used measures of functional connectivity (activity in the default mode network) is highly dependent on the integrity of white matter connections between the two hemispheres (corpus callosum) and within the cingulate bundles. Importantly, the discovery of this complex relationship of connectivity was entirely facilitated by the signal processing and fusion techniques presented herein and could not have been revealed through separate analyses of both data types as is typically performed in the majority of neuroimaging experiments. We conclude by discussing future applications of this technique to other areas of neuroimaging and examining potential limitations of the

  13. Epigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs.

    PubMed

    Amin, Viren; Harris, R Alan; Onuchic, Vitor; Jackson, Andrew R; Charnecki, Tim; Paithankar, Sameer; Lakshmi Subramanian, Sai; Riehle, Kevin; Coarfa, Cristian; Milosavljevic, Aleksandar

    2015-02-18

    Tissue-specific expression of lincRNAs suggests developmental and cell-type-specific functions, yet tissue specificity was established for only a small fraction of lincRNAs. Here, by analysing 111 reference epigenomes from the NIH Roadmap Epigenomics project, we determine tissue-specific epigenetic regulation for 3,753 (69% examined) lincRNAs, with 54% active in one of the 14 cell/tissue clusters and an additional 15% in two or three clusters. A larger fraction of lincRNA TSSs is marked in a tissue-specific manner by H3K4me1 than by H3K4me3. The tissue-specific lincRNAs are strongly linked to tissue-specific pathways and undergo distinct chromatin state transitions during cellular differentiation. Polycomb-regulated lincRNAs reside in the bivalent state in embryonic stem cells and many of them undergo H3K27me3-mediated silencing at early stages of differentiation. The exquisitely tissue-specific epigenetic regulation of lincRNAs and the assignment of a majority of them to specific tissue types will inform future studies of this newly discovered class of genes.

  14. Monte Carlo Modeling of Photon Propagation Reveals Highly Scattering Coral Tissue

    PubMed Central

    Wangpraseurt, Daniel; Jacques, Steven L.; Petrie, Tracy; Kühl, Michael

    2016-01-01

    Corals are very efficient at using solar radiation, with photosynthetic quantum efficiencies approaching theoretical limits. Here, we investigated potential mechanisms underlying such outstanding photosynthetic performance through extracting inherent optical properties of the living coral tissue and skeleton in a massive faviid coral. Using Monte Carlo simulations developed for medical tissue optics it is shown that for the investigated faviid coral, the coral tissue was a strongly light scattering matrix with a reduced scattering coefficient of μs’ = 10 cm-1 (at 636 nm). In contrast, the scattering coefficient of the coral skeleton was μs’ = 3.4 cm-1, which facilitated the efficient propagation of light to otherwise shaded coral tissue layers, thus supporting photosynthesis in lower tissues. Our study provides a quantification of coral tissue optical properties in a massive faviid coral and suggests a novel light harvesting strategy, where tissue and skeletal optics act in concert to optimize the illumination of the photosynthesizing algal symbionts embedded within the living coral tissue. PMID:27708657

  15. Anticipated Intraoperative Electron Beam Boost, External Beam Radiation Therapy, and Limb-Sparing Surgical Resection for Patients with Pediatric Soft-Tissue Sarcomas of the Extremity: A Multicentric Pooled Analysis of Long-Term Outcomes

    SciTech Connect

    Sole, Claudio V.; Calvo, Felipe A.; Polo, Alfredo; Cambeiro, Mauricio; Alvarez, Ana; Gonzalez, Carmen; Gonzalez, Jose; San Julian, Mikel; Martinez-Monge, Rafael

    2014-09-01

    Purpose: To perform a joint analysis of data from 3 contributing centers within the intraoperative electron-beam radiation therapy (IOERT)-Spanish program, to determine the potential of IOERT as an anticipated boost before external beam radiation therapy in the multidisciplinary treatment of pediatric extremity soft-tissue sarcomas. Methods and Materials: From June 1993 to May 2013, 62 patients (aged <21 years) with a histologic diagnosis of primary extremity soft-tissue sarcoma with absence of distant metastases, undergoing limb-sparing grossly resected surgery, external beam radiation therapy (median dose 40 Gy) and IOERT (median dose 10 Gy) were considered eligible for this analysis. Results: After a median follow-up of 66 months (range, 4-235 months), 10-year local control, disease-free survival, and overall survival was 85%, 76%, and 81%, respectively. In multivariate analysis after adjustment for other covariates, tumor size >5 cm (P=.04) and R1 margin status (P=.04) remained significantly associated with local relapse. In regard to overall survival only margin status (P=.04) retained association on multivariate analysis. Ten patients (16%) reported severe chronic toxicity events (all grade 3). Conclusions: An anticipated IOERT boost allowed for external beam radiation therapy dose reduction, with high local control and acceptably low toxicity rates. The combined radiosurgical approach needs to be tested in a prospective trial to confirm these results.

  16. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb (14)C.

    PubMed

    Heinemeier, Katja Maria; Schjerling, Peter; Heinemeier, Jan; Magnusson, Stig Peter; Kjaer, Michael

    2013-05-01

    Tendons are often injured and heal poorly. Whether this is caused by a slow tissue turnover is unknown, since existing data provide diverging estimates of tendon protein half-life that range from 2 mo to 200 yr. With the purpose of determining life-long turnover of human tendon tissue, we used the (14)C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of (14)C, produced by nuclear bomb tests in 1955-1963, which is reflected in all living organisms. Levels of (14)C were measured in 28 forensic samples of Achilles tendon core and 4 skeletal muscle samples (donor birth years 1945-1983) with accelerator mass spectrometry (AMS) and compared to known atmospheric levels to estimate tissue turnover. We found that Achilles tendon tissue retained levels of (14)C corresponding to atmospheric levels several decades before tissue sampling, demonstrating a very limited tissue turnover. The tendon concentrations of (14)C approximately reflected the atmospheric levels present during the first 17 yr of life, indicating that the tendon core is formed during height growth and is essentially not renewed thereafter. In contrast, (14)C levels in muscle indicated continuous turnover. Our observation provides a fundamental premise for understanding tendon function and pathology, and likely explains the poor regenerative capacity of tendon tissue.

  17. Dynamic full field optical coherence tomography: subcellular metabolic contrast revealed in tissues by interferometric signals temporal analysis

    PubMed Central

    Apelian, Clement; Harms, Fabrice; Thouvenin, Olivier; Boccara, A. Claude

    2016-01-01

    We developed a new endogenous approach to reveal subcellular metabolic contrast in fresh ex vivo tissues taking advantage of the time dependence of the full field optical coherence tomography interferometric signals. This method reveals signals linked with local activity of the endogenous scattering elements which can reveal cells where other OCT-based techniques fail or need exogenous contrast agents. We benefit from the micrometric transverse resolution of full field OCT to image intracellular features. We used this time dependence to identify different dynamics at the millisecond scale on a wide range of organs in normal or pathological conditions. PMID:27446672

  18. Live Imaging of Axolotl Digit Regeneration Reveals Spatiotemporal Choreography of Diverse Connective Tissue Progenitor Pools.

    PubMed

    Currie, Joshua D; Kawaguchi, Akane; Traspas, Ricardo Moreno; Schuez, Maritta; Chara, Osvaldo; Tanaka, Elly M

    2016-11-21

    Connective tissues-skeleton, dermis, pericytes, fascia-are a key cell source for regenerating the patterned skeleton during axolotl appendage regeneration. This complexity has made it difficult to identify the cells that regenerate skeletal tissue. Inability to identify these cells has impeded a mechanistic understanding of blastema formation. By tracing cells during digit tip regeneration using brainbow transgenic axolotls, we show that cells from each connective tissue compartment have distinct spatial and temporal profiles of proliferation, migration, and differentiation. Chondrocytes proliferate but do not migrate into the regenerate. In contrast, pericytes proliferate, then migrate into the blastema and give rise solely to pericytes. Periskeletal cells and fibroblasts contribute the bulk of digit blastema cells and acquire diverse fates according to successive waves of migration that choreograph their proximal-distal and tissue contributions. We further show that platelet-derived growth factor signaling is a potent inducer of fibroblast migration, which is required to form the blastema.

  19. Double triangular resection for a widely prolapsed posterior mitral leaflet†

    PubMed Central

    Sawazaki, Masaru; Tomari, Shiro; Tsunekawa, Tomohiro; Izawa, Naoto

    2013-01-01

    A wide and redundant prolapse of the posterior mitral leaflet in active infective endocarditis cannot be easily repaired. A sliding plasty can be attempted, but the range of annular plication is often too large. Chordal replacement is another option, but is prone to long-term degeneration because the redundant leaflet still exists. Here, we describe a simple resection technique that utilizes only two small triangular resections. The resections are sutured with no need to shorten the annulus. The leaflet tissue between the two triangular resections must be preserved to make an appropriately shaped posterior leaflet. PMID:23223672

  20. Laparoscopic Colon Resection

    MedlinePlus

    ... inches to complete the procedure. What are the Advantages of Laparoscopic Colon Resection? Results may vary depending ... type of procedure and patient’s overall condition. Common advantages are: Less postoperative pain May shorten hospital stay ...

  1. Prostate resection - minimally invasive

    MedlinePlus

    ... invasive - discharge Transurethral resection of the prostate - discharge Review Date 6/29/2015 Updated by: Jennifer Sobol, ... the Michigan Institute of Urology, West Bloomfield, MI. Review provided by VeriMed Healthcare Network. Also reviewed by ...

  2. Large bowel resection - discharge

    MedlinePlus

    ... 26. Read More Colon cancer Colostomy Crohn disease Intestinal obstruction Large bowel resection Ulcerative colitis Patient Instructions Bland ... Diseases Colonic Polyps Colorectal Cancer Diverticulosis and Diverticulitis Intestinal Obstruction Ulcerative Colitis Browse the Encyclopedia A.D.A. ...

  3. Small bowel resection - discharge

    MedlinePlus

    ... chap 26. Read More Colon cancer Crohn disease Intestinal obstruction Small bowel resection Patient Instructions Bland diet Crohn ... Editorial team. Related MedlinePlus Health Topics Intestinal Cancer Intestinal Obstruction Small Intestine Disorders Browse the Encyclopedia A.D. ...

  4. High-throughput proteomics reveal alarmins as amplifiers of tissue pathology and inflammation after spinal cord injury

    PubMed Central

    Didangelos, Athanasios; Puglia, Michele; Iberl, Michaela; Sanchez-Bellot, Candela; Roschitzki, Bernd; Bradbury, Elizabeth J.

    2016-01-01

    Spinal cord injury is characterized by acute cellular and axonal damage followed by aggressive inflammation and pathological tissue remodelling. The biological mediators underlying these processes are still largely unknown. Here we apply an innovative proteomics approach targeting the enriched extracellular proteome after spinal cord injury for the first time. Proteomics revealed multiple matrix proteins not previously associated with injured spinal tissue, including small proteoglycans involved in cell-matrix adhesion and collagen fibrillogenesis. Network analysis of transcriptomics and proteomics datasets uncovered persistent overexpression of extracellular alarmins that can trigger inflammation via pattern recognition receptors. In mechanistic experiments, inhibition of toll-like receptor-4 (TLR4) and the receptor for advanced glycation end-products (RAGE) revealed the involvement of alarmins in inflammatory gene expression, which was found to be dominated by IL1 and NFκΒ signalling. Extracellular high-mobility group box-1 (HMGB1) was identified as the likely endogenous regulator of IL1 expression after injury. These data reveal a novel tissue remodelling signature and identify endogenous alarmins as amplifiers of the inflammatory response that promotes tissue pathology and impedes neuronal repair after spinal cord injury. PMID:26899371

  5. Huge Lymphangioma of the Esophagus Resected by Endoscopic Piecemeal Mucosal Resection

    PubMed Central

    Ye, Liping; Wu, Weidan; Zheng, Haihong

    2017-01-01

    We present an unusual case of a 41-year-old male patient with a large lymphangioma of the esophagus. Endoscopy revealed that the structure measured 60 × 10 mm in the mucosa and the submucosa and had a heterogenous echo pattern. The esophageal mass was successfully resected by endoscopic piecemeal mucosal resection. However, most esophageal lymphangiomas that are larger than 2 cm in diameter reported in the literature can be removed only through open surgery. Thus far, we know of no reported cases of endoscopic resection as a treatment for this case.

  6. A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood

    PubMed Central

    Rebo, Justin; Mehdipour, Melod; Gathwala, Ranveer; Causey, Keith; Liu, Yan; Conboy, Michael J.; Conboy, Irina M.

    2016-01-01

    Heterochronic parabiosis rejuvenates the performance of old tissue stem cells at some expense to the young, but whether this is through shared circulation or shared organs is unclear. Here we show that heterochronic blood exchange between young and old mice without sharing other organs, affects tissues within a few days, and leads to different outcomes than heterochronic parabiosis. Investigating muscle, liver and brain hippocampus, in the presence or absence of muscle injury, we find that, in many cases, the inhibitory effects of old blood are more pronounced than the benefits of young, and that peripheral tissue injury compounds the negative effects. We also explore mechanistic explanations, including the role of B2M and TGF-beta. We conclude that, compared with heterochronic parabiosis, heterochronic blood exchange in small animals is less invasive and enables better-controlled studies with more immediate translation to therapies for humans. PMID:27874859

  7. The cellular and molecular mechanisms of tissue repair and regeneration as revealed by studies in Xenopus

    PubMed Central

    Li, Jingjing; Zhang, Siwei

    2016-01-01

    Abstract Survival of any living organism critically depends on its ability to repair and regenerate damaged tissues and/or organs during its lifetime following injury, disease, or aging. Various animal models from invertebrates to vertebrates have been used to investigate the molecular and cellular mechanisms of wound healing and tissue regeneration. It is hoped that such studies will form the framework for identifying novel clinical treatments that will improve the healing and regenerative capacity of humans. Amongst these models, Xenopus stands out as a particularly versatile and powerful system. This review summarizes recent findings using this model, which have provided fundamental knowledge of the mechanisms responsible for efficient and perfect tissue repair and regeneration. PMID:27800170

  8. Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases

    PubMed Central

    Marbach, Daniel; Lamparter, David; Quon, Gerald; Kellis, Manolis; Kutalik, Zoltán; Bergmann, Sven

    2016-01-01

    Mapping the molecular circuits that are perturbed by genetic variants underlying complex traits and diseases remains a great challenge. We present a comprehensive resource of 394 cell type and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity between transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) shows that disease-associated genetic variants — including variants that do not reach genome-wide significance — often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues. PMID:26950747

  9. Single cell sequencing reveals low levels of aneuploidy across mammalian tissues

    PubMed Central

    Knouse, Kristin A.; Wu, Jie; Whittaker, Charles A.; Amon, Angelika

    2014-01-01

    Whole-chromosome copy number alterations, also known as aneuploidy, are associated with adverse consequences in most cells and organisms. However, high frequencies of aneuploidy have been reported to occur naturally in the mammalian liver and brain, fueling speculation that aneuploidy provides a selective advantage in these organs. To explore this paradox, we used single cell sequencing to obtain a genome-wide, high-resolution assessment of chromosome copy number alterations in mouse and human tissues. We find that aneuploidy occurs much less frequently in the liver and brain than previously reported and is no more prevalent in these tissues than in skin. Our results highlight the rarity of chromosome copy number alterations across mammalian tissues and argue against a positive role for aneuploidy in organ function. Cancer is therefore the only known example, in mammals, of altering karyotype for functional adaptation. PMID:25197050

  10. Single cell sequencing reveals low levels of aneuploidy across mammalian tissues.

    PubMed

    Knouse, Kristin A; Wu, Jie; Whittaker, Charles A; Amon, Angelika

    2014-09-16

    Whole-chromosome copy number alterations, also known as aneuploidy, are associated with adverse consequences in most cells and organisms. However, high frequencies of aneuploidy have been reported to occur naturally in the mammalian liver and brain, fueling speculation that aneuploidy provides a selective advantage in these organs. To explore this paradox, we used single cell sequencing to obtain a genome-wide, high-resolution assessment of chromosome copy number alterations in mouse and human tissues. We find that aneuploidy occurs much less frequently in the liver and brain than previously reported and is no more prevalent in these tissues than in skin. Our results highlight the rarity of chromosome copy number alterations across mammalian tissues and argue against a positive role for aneuploidy in organ function. Cancer is therefore the only known example, in mammals, of altering karyotype for functional adaptation.

  11. Information Theoretical Analysis of a Bovine Gene Atlas Reveals Chromosomal Regions with Tissue Specific Gene Expression.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An essential step to understanding the genomic biology of any organism is to comprehensively survey its transcriptome. We present the Bovine Gene Atlas (BGA) a compendium of over 7.2 million unique 20 base Illumina DGE tags representing 100 tissue transcriptomes collected primarily from L1 Dominette...

  12. Metabolite Profiling of Preneoplastic and Neoplastic Lesions of Oral Cavity Tissue Samples Revealed a Biomarker Pattern

    PubMed Central

    Musharraf, Syed Ghulam; Shahid, Najia; Naqvi, Syed Muhammad Ali; Saleem, Mahwish; Siddiqui, Amna Jabbar; Ali, Anwar

    2016-01-01

    Oral cancer is a major health challenge in the Indian subcontinent and a dreadful form of cancers worldwide. The current study is focused on the identification of distinguished metabolites of oral cancer tissue samples in comparison with precancerous and control tissue samples using gas chromatography coupled with triple quadrupole tandem mass spectrometry and chemometric analyses. Metabolites obtained were identified through National Institute of Standards and Technology (NIST) mass spectral (Wiley registry) library. Mass Profiler Professional (MPP) software was used for the alignment and for all the statistical analysis. 31 compounds out of 735 found distinguishing among oral cancer, precancerous and control group samples using p-value ≤ 0.05. Partial Least Square Discriminant Analysis (PLSDA) model was generated using statistically significant metabolites gave an overall accuracy of 90.2%. Down-regulated amino acid levels appear to be the result of enhanced energy metabolism or up-regulation of the appropriate biosynthetic pathways, and required cell proliferation in cancer tissues. These results suggest that tissue metabolic profiles have great potential in detecting oral cancer and may aid in understanding its underlying mechanisms. PMID:27958349

  13. Comparative genomics reveals tissue-specific regulation of prolactin receptor gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prolactin (PRL), acting via the prolactin receptor, fulfills a diversity of biological functions including the maintenance of solute balance and mineral homeostasis via tissues such as the heart, kidneys and intestine. Expression and activity of the prolactin receptor (PRLR) is regulated by various ...

  14. Multi-tissue omics analyses reveal molecular regulatory networks for puberty in composite beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Puberty is a complex physiological event by which animals mature into an adult capable of sexual reproduction. In order to enhance our understanding of the genes and regulatory pathways and networks involved in puberty, we characterized the transcriptome of five reproductive tissues (i.e., hypothal...

  15. Analysis of circadian pattern reveals tissue-specific alternative transcription in leptin signaling pathway

    PubMed Central

    Ptitsyn, Andrey A; Gimble, Jeffrey M

    2007-01-01

    Background It has been previously reported that most mammalian genes display a circadian oscillation in their baseline expression. Consequently, the phase and amplitude of each component of a signal transduction cascade has downstream consequences. Results Here, we report our analysis of alternative transcripts in the leptin signaling pathway which is responsible for the systemic regulation of macronutrient storage and energy balance. We focused on the circadian expression pattern of a critical component of the leptin signaling system, suppressor of cytokine signaling 3 (SOCS3). On an Affymetrix GeneChip 430A2 microarray, this gene is represented by three probe sets targeting different regions within the 3' end of the last exon. We demonstrate that in murine brown adipose tissue two downstream 3' probe sets experience circadian baseline oscillation in counter-phase to the upstream probe set. Such differences in expression patterns are a telltale sign of alternative splicing within the last exon of SOCS3. In contrast, all three probe sets oscillated in a common phase in murine liver and white adipose tissue. This suggests that the regulation of SOCS3 expression in brown fat is tissue specific. Another component of the signaling pathway, Janus kinase (JAK), is directly regulated by SOCS and has alternative transcript probe sets oscillating in counter-phase in a white adipose tissue specific manner. Conclusion We hypothesize that differential oscillation of alternative transcripts may provide a mechanism to maintain steady levels of expression in spite of circadian baseline variation. PMID:18047714

  16. Six Tissue Transcriptomics Reveals Specific Immune Suppression in Spleen by Dietary Polyunsaturated Fatty Acids

    PubMed Central

    Gabrielsson, Britt G.; Peris, Eduard; Nookaew, Intawat; Grahnemo, Louise; Sandberg, Ann-Sofie; Wernstedt Asterholm, Ingrid; Jansson, John-Olov; Nielsen, Jens

    2016-01-01

    Dietary polyunsaturated fatty acids (PUFA) are suggested to modulate immune function, but the effects of dietary fatty acids composition on gene expression patterns in immune organs have not been fully characterized. In the current study we investigated how dietary fatty acids composition affects the total transcriptome profile, and especially, immune related genes in two immune organs, spleen (SPL) and bone marrow cells (BMC). Four tissues with metabolic function, skeletal muscle (SKM), white adipose tissue (WAT), brown adipose tissue (BAT), and liver (LIV), were investigated as a comparison. Following 8 weeks on low fat diet (LFD), high fat diet (HFD) rich in saturated fatty acids (HFD-S), or HFD rich in PUFA (HFD-P), tissue transcriptomics were analyzed by microarray and metabolic health assessed by fasting blood glucose level, HOMA-IR index, oral glucose tolerance test as well as quantification of crown-like structures in WAT. HFD-P corrected the metabolic phenotype induced by HFD-S. Interestingly, SKM and BMC were relatively inert to the diets, whereas the two adipose tissues (WAT and BAT) were mainly affected by HFD per se (both HFD-S and HFD-P). In particular, WAT gene expression was driven closer to that of the immune organs SPL and BMC by HFDs. The LIV exhibited different responses to both of the HFDs. Surprisingly, the spleen showed a major response to HFD-P (82 genes differed from LFD, mostly immune genes), while it was not affected at all by HFD-S (0 genes differed from LFD). In conclusion, the quantity and composition of dietary fatty acids affected the transcriptome in distinct manners in different organs. Remarkably, dietary PUFA, but not saturated fat, prompted a specific regulation of immune related genes in the spleen, opening the possibility that PUFA can regulate immune function by influencing gene expression in this organ. PMID:27166587

  17. Matrix factorization reveals aging-specific co-expression gene modules in the fat and muscle tissues in nonhuman primates

    NASA Astrophysics Data System (ADS)

    Wang, Yongcui; Zhao, Weiling; Zhou, Xiaobo

    2016-10-01

    Accurate identification of coherent transcriptional modules (subnetworks) in adipose and muscle tissues is important for revealing the related mechanisms and co-regulated pathways involved in the development of aging-related diseases. Here, we proposed a systematically computational approach, called ICEGM, to Identify the Co-Expression Gene Modules through a novel mathematical framework of Higher-Order Generalized Singular Value Decomposition (HO-GSVD). ICEGM was applied on the adipose, and heart and skeletal muscle tissues in old and young female African green vervet monkeys. The genes associated with the development of inflammation, cardiovascular and skeletal disorder diseases, and cancer were revealed by the ICEGM. Meanwhile, genes in the ICEGM modules were also enriched in the adipocytes, smooth muscle cells, cardiac myocytes, and immune cells. Comprehensive disease annotation and canonical pathway analysis indicated that immune cells, adipocytes, cardiomyocytes, and smooth muscle cells played a synergistic role in cardiac and physical functions in the aged monkeys by regulation of the biological processes associated with metabolism, inflammation, and atherosclerosis. In conclusion, the ICEGM provides an efficiently systematic framework for decoding the co-expression gene modules in multiple tissues. Analysis of genes in the ICEGM module yielded important insights on the cooperative role of multiple tissues in the development of diseases.

  18. Matrix factorization reveals aging-specific co-expression gene modules in the fat and muscle tissues in nonhuman primates

    PubMed Central

    Wang, Yongcui; Zhao, Weiling; Zhou, Xiaobo

    2016-01-01

    Accurate identification of coherent transcriptional modules (subnetworks) in adipose and muscle tissues is important for revealing the related mechanisms and co-regulated pathways involved in the development of aging-related diseases. Here, we proposed a systematically computational approach, called ICEGM, to Identify the Co-Expression Gene Modules through a novel mathematical framework of Higher-Order Generalized Singular Value Decomposition (HO-GSVD). ICEGM was applied on the adipose, and heart and skeletal muscle tissues in old and young female African green vervet monkeys. The genes associated with the development of inflammation, cardiovascular and skeletal disorder diseases, and cancer were revealed by the ICEGM. Meanwhile, genes in the ICEGM modules were also enriched in the adipocytes, smooth muscle cells, cardiac myocytes, and immune cells. Comprehensive disease annotation and canonical pathway analysis indicated that immune cells, adipocytes, cardiomyocytes, and smooth muscle cells played a synergistic role in cardiac and physical functions in the aged monkeys by regulation of the biological processes associated with metabolism, inflammation, and atherosclerosis. In conclusion, the ICEGM provides an efficiently systematic framework for decoding the co-expression gene modules in multiple tissues. Analysis of genes in the ICEGM module yielded important insights on the cooperative role of multiple tissues in the development of diseases. PMID:27703186

  19. Optimization of Carbon Ion Treatment Plans by Integrating Tissue Specific α/β-Values for Patients with Non-Resectable Pancreatic Cancer

    PubMed Central

    Scholz, Christian; Pommer, Mira; Brons, Stephan; Prokesch, Hannah; Ecker, Swantje; Debus, Jürgen; Jäkel, Oliver; Combs, Stephanie E.; Habermehl, Daniel

    2016-01-01

    Background The aim of the thesis is to improve treatment plans of carbon ion irradiation by integrating the tissues’ specific αβ-values for patients with locally advanced pancreatic cancer (LAPC). Material and Methods Five patients with LAPC were included in this study. By the use of the treatment planning system Syngo RT Planning (Siemens, Erlangen, Germany) treatment plans with carbon ion beams have been created. Dose calculation was based on αβ-values for both organs at risk (OAR) and the tumor. Twenty-five treatment plans and thirty-five forward calculations were created. With reference to the anatomy five field configurations were included. Single Beam Optimization (SBO) and Intensity Modulated Particle Therapy (IMPT) were used for optimization. The plans were analyzed with respect to both dose distributions and individual anatomy. The plans were evaluated using a customized index. Results With regard to the target, a field setup with one single posterior field achieves the highest score in our index. Field setups made up of three fields achieve good results in OAR sparing. Nevertheless, the field setup with one field is superior in complex topographic conditions. But, allocating an αβ-value of 2 Gy to the spinal cord leads to critical high maximum doses in the spinal cord. The evaluation of dose profiles showed significant dose peaks at borders of the αβ-gradient, especially in case of a single posterior field. Conclusion Optimization with specific αβ-values allows a more accurate view on dose distribution than previously. A field setup with one single posterior field achieves good results in case of difficult topographic conditions, but leads to high maximum doses to the spinal cord. So, field setups with multiple fields seem to be more adequate in case of LAPC, being surrounded by highly radiosensitive normal tissues. PMID:27736917

  20. ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy

    PubMed Central

    El Costa, Hicham; Gouilly, Jordi; Mansuy, Jean-Michel; Chen, Qian; Levy, Claude; Cartron, Géraldine; Veas, Francisco; Al-Daccak, Reem; Izopet, Jacques; Jabrane-Ferrat, Nabila

    2016-01-01

    The outbreak of the Zika Virus (ZIKV) and its association with fetal abnormalities have raised worldwide concern. However, the cellular tropism and the mechanisms of ZIKV transmission to the fetus during early pregnancy are still largely unknown. Therefore, we ex vivo modeled the ZIKV transmission at the maternal-fetal interface using organ culture from first trimester pregnancy samples. Here, we provide evidence that ZIKV strain circulating in Brazil infects and damages tissue architecture of the maternal decidua basalis, the fetal placenta and umbilical cord. We also show that ZIKV replicates differentially in a wide range of maternal and fetal cells, including decidual fibroblasts and macrophages, trophoblasts, Hofbauer cells as well as umbilical cord mesenchymal stem cells. The striking cellular tropism of ZIKV and its cytopathic-induced tissue injury during the first trimester of pregnancy could provide an explanation for the irreversible congenital damages. PMID:27759009

  1. Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing

    PubMed Central

    Lee, Mike; Kiefel, Helena; LaJevic, Melissa D.; Macauley, Matthew S.; Kawashima, Hiroto; O'Hara, Edward; Pan, Junliang; Paulson, James C.; Butcher, Eugene C.

    2014-01-01

    Lymphocytes are recruited from blood by high-endothelial venules (HEVs). We performed transcriptomic analyses and identified molecular signatures that distinguish HEVs from capillary endothelium and that define tissue-specific HEV specialization. Capillaries displayed gene programs for vascular development. HEVs were enriched in genes for immune defense and lymphocyte migration. We identify capillary and HEV markers and candidate mechanisms for regulated lymphocyte recruitment including a lymph node HEV-selective transmembrane mucin; transcriptional control of functionally specialized carbohydrate ligands for lymphocyte L-selectin; HEV expression of molecules for transendothelial migration; and metabolic programs for lipid mediators of lymphocyte motility and chemotaxis. We also elucidate a carbohydrate recognition pathway that targets B cells to intestinal lymphoid tissues, defining CD22 as a lectin-homing receptor for mucosal HEVs. PMID:25173345

  2. Insights into Brown Adipose Tissue Physiology as Revealed by Imaging Studies

    PubMed Central

    Izzi-Engbeaya, Chioma; Salem, Victoria; Atkar, Rajveer S; Dhillo, Waljit S

    2014-01-01

    There has been resurgence in interest in brown adipose tissue (BAT) following radiological and histological identification of metabolically active BAT in adult humans. Imaging enables BAT to be studied non-invasively and therefore imaging studies have contributed a significant amount to what is known about BAT function in humans. In this review the current knowledge (derived from imaging studies) about the prevalence, function, activity and regulation of BAT in humans (as well as relevant rodent studies), will be summarized. PMID:26167397

  3. Differential tissue distribution of tryptophan hydroxylase isoforms 1 and 2 as revealed with monospecific antibodies.

    PubMed

    Sakowski, Stacey A; Geddes, Timothy J; Thomas, David M; Levi, Edi; Hatfield, James S; Kuhn, Donald M

    2006-04-26

    Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of the neurotransmitter serotonin. Once thought to be a single-gene product, TPH is now known to exist in two isoforms-TPH1 is found in the pineal and gut, and TPH2 is selectively expressed in brain. Heretofore, probes used for localization of TPH protein or mRNA could not distinguish between the TPH isoforms because of extensive homology shared by them at the nucleotide and amino acid level. We have produced monospecific polyclonal antibodies against TPH1 and TPH2 using peptide antigens from nonoverlapping sequences in the respective proteins. These antibodies allow the differentiation of TPH1 and TPH2 upon immunoblotting, immunoprecipitation, and immunocytochemical staining of tissue sections from brain and gut. TPH1 and TPH2 antibodies do not cross-react with either tyrosine hydroxylase or phenylalanine hydroxylase. Analysis of mouse tissues confirms that TPH1 is the predominant form expressed in pineal gland and in P815 mastocytoma cells with a molecular weight of 51 kDa. TPH2 is the predominant enzyme form expressed in brain extracts from mesencephalic tegmentum, striatum, and hippocampus with a molecular weight of 56 kDa. Antibody specificity against TPH1 and TPH2 is retained across mouse, rat, rabbit, primate, and human tissues. Antibodies that distinguish between the isoforms of TPH will allow studies of the differential regulation of their expression in brain and periphery.

  4. Quantitative image analysis reveals distinct structural transitions during aging in Caenorhabditis elegans tissues.

    PubMed

    Johnston, Josiah; Iser, Wendy B; Chow, David K; Goldberg, Ilya G; Wolkow, Catherine A

    2008-07-30

    Aging is associated with functional and structural declines in many body systems, even in the absence of underlying disease. In particular, skeletal muscles experience severe declines during aging, a phenomenon termed sarcopenia. Despite the high incidence and severity of sarcopenia, little is known about contributing factors and development. Many studies focus on functional aspects of aging-related tissue decline, while structural details remain understudied. Traditional approaches for quantifying structural changes have assessed individual markers at discrete intervals. Such approaches are inadequate for the complex changes associated with aging. An alternative is to consider changes in overall morphology rather than in specific markers. We have used this approach to quantitatively track tissue architecture during adulthood and aging in the C. elegans pharynx, the neuromuscular feeding organ. Using pattern recognition to analyze aged-grouped pharynx images, we identified discrete step-wise transitions between distinct morphologies. The morphology state transitions were maintained in mutants with pharynx neurotransmission defects, although the pace of the transitions was altered. Longitudinal measurements of pharynx function identified a predictive relationship between mid-life pharynx morphology and function at later ages. These studies demonstrate for the first time that adult tissues undergo distinct structural transitions reflecting postdevelopmental events. The processes that underlie these architectural changes may contribute to increased disease risk during aging, and may be targets for factors that alter the aging rate. This work further demonstrates that pattern analysis of an image series offers a novel and generally accessible approach for quantifying morphological changes and identifying structural biomarkers.

  5. The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice.

    PubMed Central

    Esther, C R; Marino, E M; Howard, T E; Machaud, A; Corvol, P; Capecchi, M R; Bernstein, K E

    1997-01-01

    Angiotensin-converting enzyme (ACE) generates the vasoconstrictor angiotensin II, which plays a critical role in maintenance of blood pressure in mammals. Although significant ACE activity is found in plasma, the majority of the enzyme is bound to tissues such as the vascular endothelium. We used targeted homologous recombination to create mice expressing a form of ACE that lacks the COOH-terminal half of the molecule. This modified ACE protein is catalytically active but entirely secreted from cells. Mice that express only this modified ACE have significant plasma ACE activity but no tissue-bound enzyme. These animals have low blood pressure, renal vascular thickening, and a urine concentrating defect. The phenotype is very similar to that of completely ACE-deficient mice previously reported, except that the renal pathology is less severe. These studies strongly support the concept that the tissue-bound ACE is essential to the control of blood pressure and the structure and function of the kidney. PMID:9153279

  6. CILAIR-Based Secretome Analysis of Obese Visceral and Subcutaneous Adipose Tissues Reveals Distinctive ECM Remodeling and Inflammation Mediators

    PubMed Central

    Roca-Rivada, Arturo; Belen Bravo, Susana; Pérez-Sotelo, Diego; Alonso, Jana; Isabel Castro, Ana; Baamonde, Iván; Baltar, Javier; Casanueva, Felipe F.; Pardo, María

    2015-01-01

    In the context of obesity, strong evidences support a distinctive pathological contribution of adipose tissue depending on its anatomical site of accumulation. Therefore, subcutaneous adipose tissue (SAT) has been lately considered metabolically benign compared to visceral fat (VAT), whose location is associated to the risk of developing cardiovascular disease, insulin resistance, and other associated comorbidities. Under the above situation, the chronic local inflammation that characterizes obese adipose tissue, has acquired a major role on the pathogenesis of obesity. In this work, we have analyzed for the first time human obese VAT and SAT secretomes using an improved quantitative proteomic approach for the study of tissue secretomes, Comparison of Isotope-Labeled Amino acid Incorporation Rates (CILAIR). The use of double isotope-labeling-CILAIR approach to analyze VAT and SAT secretomes allowed the identification of location-specific secreted proteins and its differential secretion. Additionally to the very high percentage of identified proteins previously implicated in obesity or in its comorbidities, this approach was revealed as a useful tool for the study of the obese adipose tissue microenvironment including extracellular matrix (ECM) remodeling and inflammatory status. The results herein presented reinforce the fact that VAT and SAT depots have distinct features and contribute differentially to metabolic disease. PMID:26198096

  7. Primary transcriptomes of Mycobacterium avium subsp. paratuberculosis reveal proprietary pathways in tissue and macrophages

    PubMed Central

    2010-01-01

    Background Mycobacterium avium subsp. paratuberculosis (MAP) persistently infects intestines and mesenteric lymph nodes leading to a prolonged subclinical disease. The MAP genome sequence was published in 2005, yet its transcriptional organization in natural infection is unknown. While prior research analyzed regulated gene sets utilizing defined, in vitro stress related or advanced surgical methods with various animal species, we investigated the intracellular lifestyle of MAP in the intestines and lymph nodes to understand the MAP pathways that function to govern this persistence. Results Our transcriptional analysis shows that 21%, 8% and 3% of the entire MAP genome was represented either inside tissues, macrophages or both, respectively. Transcripts belonging to latency and cell envelope biogenesis were upregulated in the intestinal tissues whereas those belonging to intracellular trafficking and secretion were upregulated inside the macrophages. Transcriptomes of natural infection and in vitro macrophage infection shared genes involved in transcription and inorganic ion transport and metabolism. MAP specific genes within large sequence polymorphisms of ancestral M. avium complex were downregulated exclusively in natural infection. Conclusions We have unveiled common and unique MAP pathways associated with persistence, cell wall biogenesis and virulence in naturally infected cow intestines, lymph nodes and in vitro infected macrophages. This dichotomy also suggests that in vitro macrophage models may be insufficient in providing accurate information on the events that transpire during natural infection. This is the first report to examine the primary transcriptome of MAP at the local infection site (i.e. intestinal tissue). Regulatory pathways that govern the lifecycle of MAP appear to be specified by tissue and cell type. While tissues show a "shut-down" of major MAP metabolic genes, infected macrophages upregulate several MAP specific genes along with a

  8. Monoamines tissue content analysis reveals restricted and site-specific correlations in brain regions involved in cognition.

    PubMed

    Fitoussi, A; Dellu-Hagedorn, F; De Deurwaerdère, P

    2013-01-01

    The dopamine (DA), noradrenalin (NA) and serotonin (5-HT) monoaminergic systems are deeply involved in cognitive processes via their influence on cortical and subcortical regions. The widespread distribution of these monoaminergic networks is one of the main difficulties in analyzing their functions and interactions. To address this complexity, we assessed whether inter-individual differences in monoamine tissue contents of various brain areas could provide information about their functional relationships. We used a sensitive biochemical approach to map endogenous monoamine tissue content in 20 rat brain areas involved in cognition, including 10 cortical areas and examined correlations within and between the monoaminergic systems. Whereas DA content and its respective metabolite largely varied across brain regions, the NA and 5-HT contents were relatively homogenous. As expected, the tissue content varied among individuals. Our analyses revealed a few specific relationships (10%) between the tissue content of each monoamine in paired brain regions and even between monoamines in paired brain regions. The tissue contents of NA, 5-HT and DA were inter-correlated with a high incidence when looking at a specific brain region. Most correlations found between cortical areas were positive while some cortico-subcortical relationships regarding the DA, NA and 5-HT tissue contents were negative, in particular for DA content. In conclusion, this work provides a useful database of the monoamine tissue content in numerous brain regions. It suggests that the regulation of these neuromodulatory systems is achieved mainly at the terminals, and that each of these systems contributes to the regulation of the other two.

  9. Physeal bridge resection.

    PubMed

    Khoshhal, Khalid I; Kiefer, Gerhard N

    2005-01-01

    Growth arrest secondary to physeal bridge formation is an uncommon but well-recognized complication of physeal fractures and other injuries. Regardless of the underlying etiology, physeal bridges may cause angular and/or longitudinal growth disturbances, with progression dependent on the remaining physeal growth potential. Physeal bridge resection and insertion of interposition material releases the tethering effect of the bridge. Physeal bridge resection has become an accepted treatment option for patients with existing or developing deformity and for those with at least 2 years or 2 cm of growth remaining. Current experimental research is focused on the use of gene therapy and other factors that enhance chondrocyte proliferation to improve the management of growth arrest. The use of cartilage and cultured chondrocytes as interposition material after physeal bridge resection is an area of active research.

  10. Laparoscopic anatomic liver resection

    PubMed Central

    Vibert, Eric; Kouider, Ali

    2004-01-01

    Background Liver resection is reputed to be one of the most difficult procedures embraced in laparoscopy. This report shows that with adequate training, anatomical liver resection including major hepatectomies can be performed. Methods This is a retrospective study. Results From 1995 to 2004, among 84 laparoscopic liver resections, 46 (54%) anatomical laparoscopic hepatectomies were performed in our institution by laparoscopy. Nine (20%) patients had benign disease while 37 (80%) had malignant lesions. Among those with malignant lesions, 14 patients had hepatocellular carcinoma (HCC), 18 had colorectal metastasis (CRM), while 5 had miscellaneous tumours. For benign disease, minor (two Couinaud's segments or less) and major anatomic hepatectomies were performed in five and four patients, respectively. For malignant lesions, minor and major anatomic hepatectomies were performed in 15 and 22 patients, respectively. Overall, conversion to laparotomy was necessary in 7 (15%) patients. Blood transfusion was required in five (10%) patients. One patient died of cerebral infarction 8 days after a massive peroperative haemorrhage. The overall morbidity rate was 34% whatever the type of resection. Three patients required reoperation, either for haemorrhage (n=1) and/or biliary leak (n=2). For CRM (n=18), overall and disease-free survival at 24 months (mean follow-up of 17 months) were 100% and 56%, respectively. For HCC (n=14), overall and disease-free survival at 36 months (mean follow-up of 29 months) were 91% and 65%, respectively. No port site metastasis occurred in patients with malignancy. Conclusions After a long training with limited liver resection in superficial segments, laparoscopic anatomical minor and major resections are feasible. Short-term carcinological results seem to be similar to those obtained with laparotomy. PMID:18333079

  11. Real-time in vivo imaging of butterfly wing development: revealing the cellular dynamics of the pupal wing tissue.

    PubMed

    Iwata, Masaki; Ohno, Yoshikazu; Otaki, Joji M

    2014-01-01

    Butterfly wings are covered with regularly arranged single-colored scales that are formed at the pupal stage. Understanding pupal wing development is therefore crucial to understand wing color pattern formation. Here, we successfully employed real-time in vivo imaging techniques to observe pupal hindwing development over time in the blue pansy butterfly, Junonia orithya. A transparent sheet of epithelial cells that were not yet regularly arranged was observed immediately after pupation. Bright-field imaging and autofluorescent imaging revealed free-moving hemocytes and tracheal branches of a crinoid-like structure underneath the epithelium. The wing tissue gradually became gray-white, epithelial cells were arranged regularly, and hemocytes disappeared, except in the bordering lacuna, after which scales grew. The dynamics of the epithelial cells and scale growth were also confirmed by fluorescent imaging. Fluorescent in vivo staining further revealed that these cells harbored many mitochondria at the surface of the epithelium. Organizing centers for the border symmetry system were apparent immediately after pupation, exhibiting a relatively dark optical character following treatment with fluorescent dyes, as well as in autofluorescent images. The wing tissue exhibited slow and low-frequency contraction pulses with a cycle of approximately 10 to 20 minutes, mainly occurring at 2 to 3 days postpupation. The pulses gradually became slower and weaker and eventually stopped. The wing tissue area became larger after contraction, which also coincided with an increase in the autofluorescence intensity that might have been caused by scale growth. Examination of the pattern of color development revealed that the black pigment was first deposited in patches in the central areas of an eyespot black ring and a parafocal element. These results of live in vivo imaging that covered wide wing area for a long time can serve as a foundation for studying the cellular dynamics of living

  12. Real-Time In Vivo Imaging of Butterfly Wing Development: Revealing the Cellular Dynamics of the Pupal Wing Tissue

    PubMed Central

    Iwata, Masaki; Ohno, Yoshikazu; Otaki, Joji M.

    2014-01-01

    Butterfly wings are covered with regularly arranged single-colored scales that are formed at the pupal stage. Understanding pupal wing development is therefore crucial to understand wing color pattern formation. Here, we successfully employed real-time in vivo imaging techniques to observe pupal hindwing development over time in the blue pansy butterfly, Junonia orithya. A transparent sheet of epithelial cells that were not yet regularly arranged was observed immediately after pupation. Bright-field imaging and autofluorescent imaging revealed free-moving hemocytes and tracheal branches of a crinoid-like structure underneath the epithelium. The wing tissue gradually became gray-white, epithelial cells were arranged regularly, and hemocytes disappeared, except in the bordering lacuna, after which scales grew. The dynamics of the epithelial cells and scale growth were also confirmed by fluorescent imaging. Fluorescent in vivo staining further revealed that these cells harbored many mitochondria at the surface of the epithelium. Organizing centers for the border symmetry system were apparent immediately after pupation, exhibiting a relatively dark optical character following treatment with fluorescent dyes, as well as in autofluorescent images. The wing tissue exhibited slow and low-frequency contraction pulses with a cycle of approximately 10 to 20 minutes, mainly occurring at 2 to 3 days postpupation. The pulses gradually became slower and weaker and eventually stopped. The wing tissue area became larger after contraction, which also coincided with an increase in the autofluorescence intensity that might have been caused by scale growth. Examination of the pattern of color development revealed that the black pigment was first deposited in patches in the central areas of an eyespot black ring and a parafocal element. These results of live in vivo imaging that covered wide wing area for a long time can serve as a foundation for studying the cellular dynamics of living

  13. Whole-genome bisulfite sequencing maps from multiple human tissues reveal novel CpG islands associated with tissue-specific regulation

    PubMed Central

    Mendizabal, Isabel; Yi, Soojin V.

    2016-01-01

    CpG islands (CGIs) are one of the most widely studied regulatory features of the human genome, with critical roles in development and disease. Despite such significance and the original epigenetic definition, currently used CGI sets are typically predicted from DNA sequence characteristics. Although CGIs are deeply implicated in practical analyses of DNA methylation, recent studies have shown that such computational annotations suffer from inaccuracies. Here we used whole-genome bisulfite sequencing from 10 diverse human tissues to identify a comprehensive, experimentally obtained, single-base resolution CGI catalog. In addition to the unparalleled annotation precision, our method is free from potential bias due to arbitrary sequence features or probe affinity differences. In addition to clarifying substantial false positives in the widely used University of California Santa Cruz (UCSC) annotations, our study identifies numerous novel epigenetic loci. In particular, we reveal significant impact of transposable elements on the epigenetic regulatory landscape of the human genome and demonstrate ubiquitous presence of transcription initiation at CGIs, including alternative promoters in gene bodies and non-coding RNAs in intergenic regions. Moreover, coordinated DNA methylation and chromatin modifications mark tissue-specific enhancers at novel CGIs. Enrichment of specific transcription factor binding from ChIP-seq supports mechanistic roles of CGIs on the regulation of tissue-specific transcription. The new CGI catalog provides a comprehensive and integrated list of genomic hotspots of epigenetic regulation. PMID:26512062

  14. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis

    PubMed Central

    Yona, Simon; Kim, Ki-Wook; Wolf, Yochai; Mildner, Alexander; Varol, Diana; Breker, Michal; Strauss-Ayali, Dalit; Viukov, Sergey; Guilliams, Martin; Misharin, Alexander; Hume, David A.; Perlman, Harris; Malissen, Bernard; Zelzer, Elazar; Jung, Steffen

    2013-01-01

    SUMMARY Mononuclear phagocytes, including monocytes, macrophages and dendritic cells, contribute to tissue integrity, as well as innate and adaptive immune defense. Emerging evidence for labour division indicates that manipulation of these cells could bear therapeutic potential. However, specific ontogenies of individual populations and the overall functional organisation of the cellular network are not well-defined. Here we report a fate mapping study of the murine monocyte and macrophage compartment taking advantage of constitutive and conditional CX3CR1 promoter-driven Cre recombinase expression. We have demonstrated that major tissue resident macrophage populations, including liver Kupffer cells, lung alveolar, splenic and peritoneal macrophages, are established prior to birth and maintain themselves subsequently during adulthood independent of replenishment by blood monocytes. Furthermore, we have established that the short-lived Ly6C+ monocytes constitute obligatory steady state precursors of blood-resident Ly6C− cells and that the abundance of Ly6C+ blood monocytes dynamically controls the circulation life span of their progeny. PMID:23273845

  15. Quantification of Calcified Particles in Human Valve Tissue Reveals Asymmetry of Calcific Aortic Valve Disease Development

    PubMed Central

    Yabusaki, Katsumi; Hutcheson, Joshua D.; Vyas, Payal; Bertazzo, Sergio; Body, Simon C.; Aikawa, Masanori; Aikawa, Elena

    2016-01-01

    Recent studies indicated that small calcified particles observable by scanning electron microscopy (SEM) may initiate calcification in cardiovascular tissues. We hypothesized that if the calcified particles precede gross calcification observed in calcific aortic valve disease (CAVD), they would exhibit a regional asymmetric distribution associated with CAVD development, which always initiates at the base of aortic valve leaflets adjacent to the aortic outflow in a region known as the fibrosa. Testing this hypothesis required counting the calcified particles in histological sections of aortic valve leaflets. SEM images, however, do not provide high contrast between components within images, making the identification and quantification of particles buried within tissue extracellular matrix difficult. We designed a new unique pattern-matching based technique to allow for flexibility in recognizing particles by creating a gap zone in the detection criteria that decreased the influence of non-particle image clutter in determining whether a particle was identified. We developed this flexible pattern particle-labeling (FpPL) technique using synthetic test images and human carotid artery tissue sections. A conventional image particle counting method (preinstalled in ImageJ) did not properly recognize small calcified particles located in noisy images that include complex extracellular matrix structures and other commonly used pattern-matching methods failed to detect the wide variation in size, shape, and brightness exhibited by the particles. Comparative experiments with the ImageJ particle counting method demonstrated that our method detected significantly more (p < 2 × 10−7) particles than the conventional method with significantly fewer (p < 0.0003) false positives and false negatives (p < 0.0003). We then applied the FpPL technique to CAVD leaflets and showed a significant increase in detected particles in the fibrosa at the base of the leaflets (p

  16. Proteomic analysis of patient tissue reveals PSA protein in the stroma of benign prostatic hyperplasia

    PubMed Central

    O’Malley, Katherine J.; Eisermann, Kurtis; Pascal, Laura E.; Parwani, Anil V.; Majima, Tsuyoshi; Graham, Lara; Hrebinko, Katherine; Acquafondata, Marie; Stewart, Nicolas A.; Nelson, Joel B.; Yoshimura, Naoki; Wang, Zhou

    2014-01-01

    BACKGROUND Benign prostatic hyperplasia (BPH) is an age-related disease frequently associated with lower urinary tract symptoms (LUTS) that involves hyperplasia of both epithelial and stromal cells. Stromal fibrosis is a distinctive feature of BPH, but the exact mechanisms underlying this phenomenon are poorly understood. METHODS In the current study, proteomics analyses were utilized to identify proteins altered in the BPH stromal compartment from patients with symptomatic BPH. Stromal cells were isolated from histological nodules of BPH by laser capture microdissection (LCM) and subjected to liquid chromatography/mass spectrometry. RESULTS Proteins identified included several stromal-specific proteins involved in extracellular matrix remodeling, focal adhesion and cellular junctions. Additionally, the proteomics array identified the presence of luminal epithelial secretory protein PSA. Immunostaining, ELISA, and in situ hybridization analyses of BPH tissues verified the presence of PSA protein but absence of PSA mRNA in the stromal compartment. E-cadherin was down-regulated in BPH epithelial cells compared to normal adjacent tissues, suggesting that alteration of cellular junctions could contribute to the presence of luminal epithelial secreted proteins PSA and KLK2 in the stromal compartment. CONCLUSIONS The above findings suggest that the presence of secreted proteins PSA and KLK2 from prostate luminal epithelial cells in BPH stroma is a hallmark of BPH nodules which could in part be due to alterations in cellular junction proteins and/or increased epithelial barrier permeability. Elucidating the cause and consequence of these secreted proteins in the stromal compartment of BPH may lead to new understanding of BPH pathogenesis as well as approaches to prevent and/or treat this common disease. PMID:24711254

  17. Intestinal adaptation following resection.

    PubMed

    Tappenden, Kelly A

    2014-05-01

    Intestinal adaptation is a natural compensatory process that occurs following extensive intestinal resection, whereby structural and functional changes in the intestine improve nutrient and fluid absorption in the remnant bowel. In animal studies, postresection structural adaptations include bowel lengthening and thickening and increases in villus height and crypt depth. Functional changes include increased nutrient transporter expression, accelerated crypt cell differentiation, and slowed transit time. In adult humans, data regarding adaptive changes are sparse, and the mechanisms underlying intestinal adaptation remain to be fully elucidated. Several factors influence the degree of intestinal adaptation that occurs post resection, including site and extent of resection, luminal stimulation with enteral nutrients, and intestinotrophic factors. Two intestinotrophic growth factors, the glucagon-like peptide 2 analog teduglutide and recombinant growth hormone (somatropin), are now approved for clinical use in patients with short bowel syndrome (SBS). Both agents enhance fluid absorption and decrease requirements for parenteral nutrition (PN) and/or intravenous fluid. Intestinal adaptation has been thought to be limited to the first 1-2 years following resection in humans. However, recent data suggest that a significant proportion of adult patients with SBS can achieve enteral autonomy, even after many years of PN dependence, particularly with trophic stimulation.

  18. Regulation of KLF4 turnover reveals an unexpected tissue specific role of pVHL in tumorigenesis

    PubMed Central

    Gamper, Armin M.; Qiao, Xinxian; Kim, Jennifer; Zhang, Liyong; DeSimone, Michelle C.; Rathmell, W. Kimryn; Wan, Yong

    2014-01-01

    SUMMARY The transcription factor Krüppel-like factor 4 (KLF4) is an important regulator of cell fate decision, including cell cycle regulation, apoptosis, and stem cell renewal, and plays an ambivalent role in tumorigenesis as a tissue specific tumor suppressor or oncogene. Here we report that the Von Hippel-Lindau gene product, pVHL, physically interacts with KLF4 and regulates its rapid turnover observed in both differentiated and stem cells. We provide mechanistic insights into KLF4 degradation and show that pVHL depletion in colorectal cancer cells leads to cell cycle arrest concomitant with increased transcription of the KLF4-dependent p21 gene. Finally, immunohistochemical staining revealed elevated pVHL and reduced KLF4 levels in colon cancer tissues. We therefore propose that unexpectedly pVHL, via the degradation of KLF4, is a facilitating factor in colorectal tumorigenesis. PMID:22284679

  19. An analysis of the expression of cyclophilin C reveals tissue restriction and an intriguing pattern in the mouse kidney.

    PubMed Central

    Friedman, J.; Weissman, I.; Friedman, J.; Alpert, S.

    1994-01-01

    Cyclophilin C (cyp C) is a cyclosporin A (CsA) binding protein originally isolated from a mouse bone marrow stromal cell line. We have compared the expression patterns of the mammalian cyclophilins A, B, and C in mouse tissues using in situ hybridization. These studies reveal that cyp C is expressed in a restricted subset of tissues including mouse ovary, testis, bone marrow, and kidney. Within the kidney, cyp C is highly expressed in a narrow zone in the outer medulla. Using monoclonal antibodies reactive against cyp C, we find that the kidney cells expressing cyp C correspond to the S3 segment of the nephron. The S3 segment has been shown to sustain histopathological damage from high dosages of CsA, raising the possibility that cyp C may be involved in mediating this damage. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8203464

  20. Transcriptome Sequencing Reveals the Character of Incomplete Dosage Compensation across Multiple Tissues in Flycatchers

    PubMed Central

    Uebbing, Severin; Künstner, Axel; Mäkinen, Hannu; Ellegren, Hans

    2013-01-01

    Sex chromosome divergence, which follows the cessation of recombination and degeneration of the sex-limited chromosome, can cause a reduction in expression level for sex-linked genes in the heterozygous sex, unless some mechanisms of dosage compensation develops to counter the reduction in gene dose. Because large-scale perturbations in expression levels arising from changes in gene dose might have strong deleterious effects, the evolutionary response should be strong. However, in birds and in at least some other female heterogametic organisms, wholesale sex chromosome dosage compensation does not seem to occur. Using RNA-seq of multiple tissues and individuals, we investigated male and female expression levels of Z-linked and autosomal genes in the collared flycatcher, a bird for which a draft genome sequence recently has been reported. We found that male expression of Z-linked genes was on average 50% higher than female expression, although there was considerable variation in the male-to-female ratio among genes. The ratio for individual genes was well correlated among tissues and there was also a correlation in the extent of compensation between flycatcher and chicken orthologs. The relative excess of male expression was positively correlated with expression breadth, expression level, and number of interacting proteins (protein connectivity), and negatively correlated with variance in expression. These observations lead to a model of compensation occurring on a gene-by-gene basis, supported by an absence of clustering of genes on the Z chromosome with respect to the extent of compensation. Equal mean expression level of autosomal and Z-linked genes in males, and 50% higher expression of autosomal than Z-linked genes in females, is compatible with that partial compensation is achieved by hypertranscription from females’ single Z chromosome. A comparison with male-to-female expression ratios in orthologous Z-linked genes of ostriches, where Z–W recombination

  1. Comprehensive discovery of DNA motifs in 349 human cells and tissues reveals new features of motifs.

    PubMed

    Zheng, Yiyu; Li, Xiaoman; Hu, Haiyan

    2015-01-01

    Comprehensive motif discovery under experimental conditions is critical for the global understanding of gene regulation. To generate a nearly complete list of human DNA motifs under given conditions, we employed a novel approach to de novo discover significant co-occurring DNA motifs in 349 human DNase I hypersensitive site datasets. We predicted 845 to 1325 motifs in each dataset, for a total of 2684 non-redundant motifs. These 2684 motifs contained 54.02 to 75.95% of the known motifs in seven large collections including TRANSFAC. In each dataset, we also discovered 43 663 to 2 013 288 motif modules, groups of motifs with their binding sites co-occurring in a significant number of short DNA regions. Compared with known interacting transcription factors in eight resources, the predicted motif modules on average included 84.23% of known interacting motifs. We further showed new features of the predicted motifs, such as motifs enriched in proximal regions rarely overlapped with motifs enriched in distal regions, motifs enriched in 5' distal regions were often enriched in 3' distal regions, etc. Finally, we observed that the 2684 predicted motifs classified the cell or tissue types of the datasets with an accuracy of 81.29%. The resources generated in this study are available at http://server.cs.ucf.edu/predrem/.

  2. Metabolic Profiling of Somatic Tissues from Monochamus alternatus (Coleoptera: Cerambycidae) Reveals Effects of Irradiation on Metabolism

    PubMed Central

    Qu, Liangjian; Wang, Lijuan; Wang, Qinghua; Wang, Yuzhu; Zhang, Yongan

    2014-01-01

    A high-level of sexual sterility is of importance for the sterile insect technique (SIT). However, the use of high-dose-intensity gamma radiation to induce sterility has negative impacts not only on reproductive cells but also on somatic cells. In this study, we investigated the metabolite differences in somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated male Monochamus alternatus, an important vector of the pathogenic nematode, Bursaphelenchus xylophilus, which kills Asian pines. The results showed that metabolite levels changed moderately in the 20-Gy samples but were markedly altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively. Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but were not changed significantly in the 20-Gy samples. The comprehensive metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic pathways involved in the life process. The findings presented in this manuscript will contribute to our knowledge of the characteristic metabolic changes associated with gamma-radiation-induced damage to somatic cells and will allow for better exploration of the SIT for the control of this target pest. PMID:24937685

  3. Lipidomic Profiling of Adipose Tissue Reveals an Inflammatory Signature in Cancer-Related and Primary Lymphedema

    PubMed Central

    Sedger, Lisa M.; Tull, Dedreia L.; McConville, Malcolm J.; De Souza, David P.; Rupasinghe, Thusitha W. T.; Williams, Spencer J.; Dayalan, Saravanan; Lanzer, Daniel; Mackie, Helen; Lam, Thomas C.; Boyages, John

    2016-01-01

    Cancer-related and primary lymphedema (LE) are associated with the production of adipose tissue (AT). Nothing is known, however, about the lipid-based molecules that comprise LE AT. We therefore analyzed lipid molecules in lipoaspirates and serum obtained from LE patients, and compared them to lipoaspirates from cosmetic surgery patients and healthy control cohort serum. LE patient serum analysis demonstrated that triglycerides, HDL- and LDL-cholesterol and lipid transport molecules remained within the normal range, with no alterations in individual fatty acids. The lipidomic analysis also identified 275 lipid-based molecules, including triacylglycerides, diacylglycerides, fatty acids and phospholipids in AT oil and fat. Although the majority of lipid molecules were present in a similar abundance in LE and non-LE samples, there were several small changes: increased C20:5-containing triacylglycerides, reduced C10:0 caprinic and C24:1 nervonic acids. LE AT oil also contained a signature of increased cyclopropane-type fatty acids and inflammatory mediators arachidonic acid and ceramides. Interestingly C20:5 and C22:6 omega-3-type lipids are increased in LE AT, correlating with LE years. Hence, LE AT has a normal lipid profile containing a signature of inflammation and omega-3-lipids. It remains unclear, however, whether these differences reflect a small-scale global metabolic disturbance or effects within localised inflammatory foci. PMID:27182733

  4. Metabolic profiling of somatic tissues from Monochamus alternatus (Coleoptera: Cerambycidae) reveals effects of irradiation on metabolism.

    PubMed

    Qu, Liangjian; Wang, Lijuan; Wang, Qinghua; Wang, Yuzhu; Zhang, Yongan

    2014-06-16

    A high-level of sexual sterility is of importance for the sterile insect technique (SIT). However, the use of high-dose-intensity gamma radiation to induce sterility has negative impacts not only on reproductive cells but also on somatic cells. In this study, we investigated the metabolite differences in somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated male Monochamus alternatus, an important vector of the pathogenic nematode, Bursaphelenchus xylophilus, which kills Asian pines. The results showed that metabolite levels changed moderately in the 20-Gy samples but were markedly altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively. Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but were not changed significantly in the 20-Gy samples. The comprehensive metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic pathways involved in the life process. The findings presented in this manuscript will contribute to our knowledge of the characteristic metabolic changes associated with gamma-radiation-induced damage to somatic cells and will allow for better exploration of the SIT for the control of this target pest.

  5. Integrating Proteomics and Enzyme Kinetics Reveals Tissue-Specific Types of the Glycolytic and Gluconeogenic Pathways.

    PubMed

    Wiśniewski, Jacek R; Gizak, Agnieszka; Rakus, Dariusz

    2015-08-07

    Glycolysis is the core metabolic pathway supplying energy to cells. Whereas the vast majority of studies focus on specific aspects of the process, global analyses characterizing simultaneously all enzymes involved in the process are scarce. Here, we demonstrate that quantitative label- and standard-free proteomics allows accurate determination of titers of metabolic enzymes and enables simultaneous measurements of titers and maximal enzymatic activities (Amax) of all glycolytic enzymes and the gluconeogenic fructose 1,6-bisphosphatase in mouse brain, liver and muscle. Despite occurrence of tissue-specific isoenzymes bearing different kinetic properties, the enzyme titers often correlated well with the Amax values. To provide a more general picture of energy metabolism, we analyzed titers of the enzymes in additional 7 mouse organs and in human cells. Across the analyzed samples, we identified two basic profiles: a "fast glucose uptake" one in brain and heart, and a "gluconeogenic rich" one occurring in liver. In skeletal muscles and other organs, we found intermediate profiles. Obtained data highlighted the glucose-flux-limiting role of hexokinase which activity was always 10- to 100-fold lower than the average activity of all other glycolytic enzymes. A parallel determination of enzyme titers and maximal enzymatic activities allowed determination of kcat values without enzyme purification. Results of our in-depth proteomic analysis of the mouse organs did not support the concepts of regulation of glycolysis by lysine acetylation.

  6. Cell and tissue dynamics during Tribolium embryogenesis revealed by versatile fluorescence labeling approaches

    PubMed Central

    Benton, Matthew A.; Akam, Michael; Pavlopoulos, Anastasios

    2013-01-01

    Studies on new arthropod models such as the beetle Tribolium castaneum are shifting our knowledge of embryonic patterning and morphogenesis beyond the Drosophila paradigm. In contrast to Drosophila, Tribolium embryos exhibit the short-germ type of development and become enveloped by extensive extra-embryonic membranes, the amnion and serosa. The genetic basis of these processes has been the focus of active research. Here, we complement genetic approaches with live fluorescence imaging of Tribolium embryos to make the link between gene function and morphogenetic cell behaviors during blastoderm formation and differentiation, germband condensation and elongation, and extra-embryonic development. We first show that transient labeling methods result in strong, homogeneous and persistent expression of fluorescent markers in Tribolium embryos, labeling the chromatin, membrane, cytoskeleton or combinations thereof. We then use co-injection of fluorescent markers with dsRNA for live imaging of embryos with disrupted caudal gene function caused by RNA interference. Using these approaches, we describe and compare cell and tissue dynamics in Tribolium embryos with wild-type and altered fate maps. We find that Tribolium germband condensation is effected by cell contraction and intercalation, with the latter being dependent on the anterior-posterior patterning system. We propose that germband condensation drives initiation of amnion folding, whereas expansion of the amniotic fold and closure of the amniotic cavity are likely driven by contraction of an actomyosin cable at the boundary between the amnion and serosa. Our methodology provides a comprehensive framework for testing quantitative models of patterning, growth and morphogenetic mechanisms in Tribolium and other arthropod species. PMID:23861059

  7. Cell and tissue dynamics during Tribolium embryogenesis revealed by versatile fluorescence labeling approaches.

    PubMed

    Benton, Matthew A; Akam, Michael; Pavlopoulos, Anastasios

    2013-08-01

    Studies on new arthropod models such as the beetle Tribolium castaneum are shifting our knowledge of embryonic patterning and morphogenesis beyond the Drosophila paradigm. In contrast to Drosophila, Tribolium embryos exhibit the short-germ type of development and become enveloped by extensive extra-embryonic membranes, the amnion and serosa. The genetic basis of these processes has been the focus of active research. Here, we complement genetic approaches with live fluorescence imaging of Tribolium embryos to make the link between gene function and morphogenetic cell behaviors during blastoderm formation and differentiation, germband condensation and elongation, and extra-embryonic development. We first show that transient labeling methods result in strong, homogeneous and persistent expression of fluorescent markers in Tribolium embryos, labeling the chromatin, membrane, cytoskeleton or combinations thereof. We then use co-injection of fluorescent markers with dsRNA for live imaging of embryos with disrupted caudal gene function caused by RNA interference. Using these approaches, we describe and compare cell and tissue dynamics in Tribolium embryos with wild-type and altered fate maps. We find that Tribolium germband condensation is effected by cell contraction and intercalation, with the latter being dependent on the anterior-posterior patterning system. We propose that germband condensation drives initiation of amnion folding, whereas expansion of the amniotic fold and closure of the amniotic cavity are likely driven by contraction of an actomyosin cable at the boundary between the amnion and serosa. Our methodology provides a comprehensive framework for testing quantitative models of patterning, growth and morphogenetic mechanisms in Tribolium and other arthropod species.

  8. Heat shock proteins: in vivo heat treatments reveal adipose tissue depot-specific effects.

    PubMed

    Rogers, Robert S; Beaudoin, Marie-Soleil; Wheatley, Joshua L; Wright, David C; Geiger, Paige C

    2015-01-01

    Heat treatments (HT) and the induction of heat shock proteins (HSPs) improve whole body and skeletal muscle insulin sensitivity while decreasing white adipose tissue (WAT) mass. However, HSPs in WAT have been understudied. The purpose of the present study was to examine patterns of HSP expression in WAT depots, and to examine the effects of a single in vivo HT on WAT metabolism. Male Wistar rats received HT (41°C, 20 min) or sham treatment (37°C), and 24 h later subcutaneous, epididymal, and retroperitoneal WAT depots (SCAT, eWAT, and rpWAT, respectively) were removed for ex vivo experiments and Western blotting. SCAT, eWAT, and rpWAT from a subset of rats were also cultured separately and received a single in vitro HT or sham treatment. HSP72 and HSP25 expression was greatest in more metabolically active WAT depots (i.e., eWAT and rpWAT) compared with the SCAT. Following HT, HSP72 increased in all depots with the greatest induction occurring in the SCAT. In addition, HSP25 increased in the rpWAT and eWAT, while HSP60 increased in the rpWAT only in vivo. Free fatty acid (FFA) release from WAT explants was increased following HT in the rpWAT only, and fatty acid reesterification was decreased in the rpWAT but increased in the SCAT following HT. HT increased insulin responsiveness in eWAT, but not in SCAT or rpWAT. Differences in HSP expression and induction patterns following HT further support the growing body of literature differentiating distinct WAT depots in health and disease.

  9. Multi-platform analysis of 12 cancer types reveals molecular classification within and across tissues-of-origin

    PubMed Central

    Hoadley, Katherine A.; Yau, Christina; Wolf, Denise M.; Cherniack, Andrew D.; Tamborero, David; Ng, Sam; Leiserson, Max D.M.; Niu, Beifang; McLellan, Michael D.; Uzunangelov, Vladislav; Zhang, Jiashan; Kandoth, Cyriac; Akbani, Rehan; Shen, Hui; Omberg, Larsson; Chu, Andy; Margolin, Adam A.; van’t Veer, Laura J.; Lopez-Bigas, Nuria; Laird, Peter W.; Raphael, Benjamin J.; Ding, Li; Robertson, A. Gordon; Byers, Lauren A.; Mills, Gordon B.; Weinstein, John N.; Van Waes, Carter; Chen, Zhong; Collisson, Eric A.

    2014-01-01

    Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies. PMID:25109877

  10. The low density lipoprotein receptor-related protein 1: Unique tissue-specific functions revealed by selective gene knockout studies

    PubMed Central

    Lillis, Anna P.; Van Duyn, Lauren B.; Murphy-Ullrich, Joanne E.; Strickland, Dudley K.

    2008-01-01

    The low-density lipoprotein (LDL) receptor-related protein (originally called LRP, but now referred to as LRP1) is a large endocytic receptor that is widely expressed in several tissues. LRP1 is a member of the LDL receptor family that plays diverse roles in various biological processes including lipoprotein metabolism, degradation of proteases, activation of lysosomal enzymes and cellular entry of bacterial toxins and viruses. Deletion of the LRP1 gene leads to lethality in mice, revealing a critical, but as of yet, undefined role in development. Tissue-specific gene deletion studies reveal an important contribution of LRP1 in the vasculature, central nervous system, in macrophages and in adipocytes. Three important properties of LRP1 dictate its diverse role in physiology: first, its ability to recognize more than thirty distinct ligands; second, its ability to bind a large number of cytoplasmic adaptor proteins via determinants located on its cytoplasmic domain in a phosphorylation-specific manner; and third, its ability to associate with and modulate the activity of other transmembrane receptors such as integrins and receptor tyrosine kinases. PMID:18626063

  11. MALDI imaging mass spectrometry reveals multiple clinically relevant masses in colorectal cancer using large-scale tissue microarrays.

    PubMed

    Hinsch, Andrea; Buchholz, Malte; Odinga, Sinje; Borkowski, Carina; Koop, Christina; Izbicki, Jacob R; Wurlitzer, Marcus; Krech, Till; Wilczak, Waldemar; Steurer, Stefan; Jacobsen, Frank; Burandt, Eike-Christian; Stahl, Phillip; Simon, Ronald; Sauter, Guido; Schlüter, Hartmut

    2017-01-24

    For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer we applied MALDI imaging mass spectrometry (IMS) to a tissue micro array (TMA) containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. 15 out of 27 IMS signals revealed a significant association with survival. For 7 signals (m/z 654, 776, 788, 904, 944, 975, and 1013) the absence, and for 8 signals (m/z 643, 678, 836, 886, 898, 1095, 1459, and 1477) the presence was associated with decreased life expectancy, including 5 masses (m/z 788, 836, 904, 944, and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these 5 masses resulted in a 3-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis, and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale TMAs to simultaneously identify and validate clinically useful molecular marker.

  12. New insights on human skeletal muscle tissue compartments revealed by in vivo t2 NMR relaxometry.

    PubMed

    Araujo, Ericky C A; Fromes, Yves; Carlier, Pierre G

    2014-05-20

    The spin-spin (T2) relaxation of (1)H-NMR signals in human skeletal muscle has been previously hypothesized to reveal information about myowater compartmentation. Although experimental support has been provided, no consensus has yet emerged concerning the attribution of specific anatomical compartments to the observed T2 components. Potential application of a noninvasive tool that might offer such information urges the quest for a definitive answer to this question. The purpose of this work was to obtain new information that might help elucidate the mechanism of T2 distribution in muscle. To do so, in vivo T2 relaxation data was acquired from the soleus of eight healthy volunteers using a localized Carr-Purcell-Meiboom-Gill technique. Each acquisition contained 1000 echoes with an interecho spacing of 1 ms. Data were acquired from each subject under different vascular filling preparations expected to change exclusively the extracellular water fraction. Two exponential components were systematically observed: an intermediate component (T2 ~ 32 ms) and a long component (100 < T2 < 210 ms). The relative fraction and T2 value characterizing the long component systematically increased after progressive augmentation of extracellular water volume. Characteristic relaxation behavior for each vascular filling condition was analyzed with a two-site exchange model and a three-site two-exchange model. We show that a two-site exchange model can only predict the observations for small exchange rates, much more representative of transendothelial than transcytolemmal exchange regimes. The three-site two-exchange model representing the intracellular, interstitial, and vascular spaces was capable of precisely predicting the observations for realistic transcytolemmal and transendothelial exchange rates. The estimated intrinsic relative fractions of each of these compartments corroborate with estimations from previous works and strongly suggest that the T2 relaxation from water within

  13. Laparoscope resection of ectopic corticosteroid-secreting adrenal adenoma.

    PubMed

    Wang, Xian-Ling; Dou, Jing-Tao; Gao, Jiang-Ping; Zhong, Wen-Wen; Jin, Du; Hui, Lüzhao; Lu, Ju-Ming; Mu, Yi-Ming

    2012-01-01

    Tumors originating from ectopic adrenal tissue are relatively rare. In this article, we describe a case with Cushing's syndrome caused by an ectopic adrenal adenoma. A 38 year-old male patient presenting with cushingoid appearance for 2 years was diagnosed to have ACTH-independent Cushing's syndrome based on endocrinological evaluation. Mutiple radiological examinations detected bilateral adrenal atrophy. When the images were investigated in a more expanded scope, a 3.0×3.5×5.3 cm mass was detected in the anterior of left renal hilum and left renal vein. The mass was successfully resected with intraoperative endoscopy and pathological evaluation revealed an ectopic adrenal tumor. It is suggested that when the endocrinlogically confirmed adrenal neoplasm could not be well and definitely localized, the possibility of ectopic adrenal should be presumed and further radiography examinations should extend to the field where ectopic adrenal usually presents.

  14. Xenopus mutant reveals necessity of rax for specifying the eye field which otherwise forms tissue with telencephalic and diencephalic character

    PubMed Central

    Fisher, Marilyn; Hirsch, Nicolas; Cox, Amanda; Reeder, Rollin; Carruthers, Samantha; Hall, Amanda; Stemple, Derek L.; Grainger, Robert M.

    2014-01-01

    SUMMARY The retinal anterior homeobox (rax) gene encodes a transcription factor necessary for vertebrate eye development. rax transcription is initiated at the end of gastrulation in Xenopus, and is a key part of the regulatory network specifying anterior neural plate and retina. We describe here a Xenopus tropicalis rax mutant, the first mutant analyzed in detail from a reverse genetic screen. As in other vertebrates, this nonsense mutation results in eyeless animals, and is lethal peri-metamorphosis. Tissue normally fated to form retina in these mutants instead forms tissue with characteristics of diencephalon and telencephalon. This implies that a key role of rax, in addition to defining the eye field, is in preventing alternative forebrain identities. Our data highlight that brain and retina regions are not determined by the mid-gastrula stage but are by the neural plate stage. An RNA-Seq analysis and in situ hybridization assays for early gene expression in the mutant revealed that several key eye field transcription factors (e.g. pax6, lhx2 and six6) are not dependent on rax activity through neurulation. However, these analyses identified other genes either up- or down-regulated in mutant presumptive retinal tissue. Two neural patterning genes of particular interest that appear up-regulated in the rax mutant RNA-seq analysis are hesx1 and fezf2. These genes were not previously known to be regulated by rax. The normal function of rax is to partially repress their expression by an indirect mechanism in the presumptive retina region in wildtype embryos, thus accounting for the apparent up-regulation in the rax mutant. Knock-down experiments using antisense morpholino oligonucleotides directed against hesx1 and fezf2 show that failure to repress these two genes contributes to transformation of presumptive retinal tissue into non-retinal forebrain identities in the rax mutant. PMID:25224223

  15. Xenopus mutant reveals necessity of rax for specifying the eye field which otherwise forms tissue with telencephalic and diencephalic character.

    PubMed

    Fish, Margaret B; Nakayama, Takuya; Fisher, Marilyn; Hirsch, Nicolas; Cox, Amanda; Reeder, Rollin; Carruthers, Samantha; Hall, Amanda; Stemple, Derek L; Grainger, Robert M

    2014-11-15

    The retinal anterior homeobox (rax) gene encodes a transcription factor necessary for vertebrate eye development. rax transcription is initiated at the end of gastrulation in Xenopus, and is a key part of the regulatory network specifying anterior neural plate and retina. We describe here a Xenopus tropicalis rax mutant, the first mutant analyzed in detail from a reverse genetic screen. As in other vertebrates, this nonsense mutation results in eyeless animals, and is lethal peri-metamorphosis. Tissue normally fated to form retina in these mutants instead forms tissue with characteristics of diencephalon and telencephalon. This implies that a key role of rax, in addition to defining the eye field, is in preventing alternative forebrain identities. Our data highlight that brain and retina regions are not determined by the mid-gastrula stage but are by the neural plate stage. An RNA-Seq analysis and in situ hybridization assays for early gene expression in the mutant revealed that several key eye field transcription factors (e.g. pax6, lhx2 and six6) are not dependent on rax activity through neurulation. However, these analyses identified other genes either up- or down-regulated in mutant presumptive retinal tissue. Two neural patterning genes of particular interest that appear up-regulated in the rax mutant RNA-seq analysis are hesx1 and fezf2. These genes were not previously known to be regulated by rax. The normal function of rax is to partially repress their expression by an indirect mechanism in the presumptive retina region in wildtype embryos, thus accounting for the apparent up-regulation in the rax mutant. Knock-down experiments using antisense morpholino oligonucleotides directed against hesx1 and fezf2 show that failure to repress these two genes contributes to transformation of presumptive retinal tissue into non-retinal forebrain identities in the rax mutant.

  16. Reconstruction after resection of malignant parapharyngeal space tumor

    PubMed Central

    Umezawa, Hiroki; Nakamizo, Munenaga; Yokoshima, Kazuhiko; Nara, Shimpei; Ogawa, Rei; Hyakusoku, Hiko

    2014-01-01

    Abstract Primary malignant tumor of the parapharyngeal space (PPS) is rare. After surgical resection, primary closure could be considered if the oropharynx mucosa remains. This report describes two patients who underwent reconstruction by free tissue transfer after the resection of PPS tumors. This report was presented at the 56th annual meeting of the Japanese Society of Plastic and Reconstructive Surgery, 4 April, 2013. PMID:27252950

  17. Systems Analysis of the Dynamic Inflammatory Response to Tissue Damage Reveals Spatiotemporal Properties of the Wound Attractant Gradient.

    PubMed

    Weavers, Helen; Liepe, Juliane; Sim, Aaron; Wood, Will; Martin, Paul; Stumpf, Michael P H

    2016-08-08

    In the acute inflammatory phase following tissue damage, cells of the innate immune system are rapidly recruited to sites of injury by pro-inflammatory mediators released at the wound site. Although advances in live imaging allow us to directly visualize this process in vivo, the precise identity and properties of the primary immune damage attractants remain unclear, as it is currently impossible to directly observe and accurately measure these signals in tissues. Here, we demonstrate that detailed information about the attractant signals can be extracted directly from the in vivo behavior of the responding immune cells. By applying inference-based computational approaches to analyze the in vivo dynamics of the Drosophila inflammatory response, we gain new detailed insight into the spatiotemporal properties of the attractant gradient. In particular, we show that the wound attractant is released by wound margin cells, rather than by the wounded tissue per se, and that it diffuses away from this source at rates far slower than those of previously implicated signals such as H2O2 and ATP, ruling out these fast mediators as the primary chemoattractant. We then predict, and experimentally test, how competing attractant signals might interact in space and time to regulate multi-step cell navigation in the complex environment of a healing wound, revealing a period of receptor desensitization after initial exposure to the damage attractant. Extending our analysis to model much larger wounds, we uncover a dynamic behavioral change in the responding immune cells in vivo that is prognostic of whether a wound will subsequently heal or not. VIDEO ABSTRACT.

  18. Biospectroscopy reveals the effect of varying water quality on tadpole tissues of the common frog (Rana temporaria).

    PubMed

    Strong, Rebecca J; Halsall, Crispin J; Ferenčík, Martin; Jones, Kevin C; Shore, Richard F; Martin, Francis L

    2016-06-01

    Amphibians are undergoing large population declines in many regions around the world. As environmental pollution from both agricultural and urban sources has been implicated in such declines, there is a need for a biomonitoring approach to study potential impacts on this vulnerable class of organism. This study assessed the use of infrared (IR) spectroscopy as a tool to detect changes in several tissues (liver, muscle, kidney, heart and skin) of late-stage common frog (Rana temporaria) tadpoles collected from ponds with differing water quality. Small differences in spectral signatures were revealed between a rural agricultural pond and an urban pond receiving wastewater and landfill run-off; these were limited to the liver and heart, although large differences in body size were apparent, surprisingly with tadpoles from the urban site larger than those from the rural site. Large differences in liver spectra were found between tadpoles from the pesticide and nutrient impacted pond compared to the rural agricultural pond, particularly in regions associated with lipids. Liver mass and hepatosomatic indices were found to be significantly increased in tadpoles from the site impacted by pesticides and trace organic chemicals, suggestive of exposure to environmental contamination. Significant alterations were also found in muscle tissue between tadpoles from these two ponds in regions associated with glycogen, potentially indicative of a stress response. This study highlights the use of IR spectroscopy, a low-cost, rapid and reagent-free technique in the biomonitoring of a class of organisms susceptible to environmental degradation.

  19. Color-Doppler sonographic tissue perfusion measurements reveal significantly diminished renal cortical perfusion in kidneys with vesicoureteral reflux

    PubMed Central

    Scholbach, T. M.; Sachse, C.

    2016-01-01

    Vesicoureteral reflux (VUR) and its sequelae may lead to reduced renal perfusion and loss of renal function. Methods to describe and monitor tissue perfusion are needed. We investigated dynamic tissue perfusion measurement (DTPM) with the PixelFlux-software to measure microvascular changes in the renal cortex in 35 children with VUR and 28 healthy children. DTPM of defined horizontal slices of the renal cortex was carried out. A kidney was assigned to the “low grade reflux”-group if the reflux grade of the voiding cystourethrogram was 1 to 3 and to the “high grade reflux”-group if the reflux grade was 4 to 5. Kidneys with VUR showed a significantly reduced cortical perfusion. Compared to healthy kidneys, this decline reached in low and high grade refluxes within the proximal 50% of the cortex: 3% and 12 %, in the distal 50% of the cortex: 21% and 44 % and in the most distal 20 % of the cortex 41% and 44%. DTPM reveals a perfusion loss in kidneys depending on the degree of VUR, which is most pronounced in the peripheral cortex. Thus, DTPM offers the tool to evaluate microvascular perfusion, to help planning treatment decisions in children with VUR. PMID:27051133

  20. The E3 ligase axotrophin/MARCH-7: protein expression profiling of human tissues reveals links to adult stem cells.

    PubMed

    Szigyarto, Cristina A; Sibbons, Paul; Williams, Gill; Uhlen, Mathias; Metcalfe, Su M

    2010-04-01

    Axotrophin/MARCH-7 was first identified in mouse embryonic stem cells as a neural stem cell gene. Using the axotrophin/MARCH-7 null mouse, we discovered profound effects on T lymphocyte responses, including 8-fold hyperproliferation and 5-fold excess release of the stem cell cytokine leukemia inhibitory factor (LIF). Our further discovery that axotrophin/MARCH-7 is required for targeted degradation of the LIF receptor subunit gp190 implies a direct role in the regulation of LIF signaling. Bioinformatics studies revealed a highly conserved RING-CH domain in common with the MARCH family of E3-ubiquitin ligases, and accordingly, axotrophin was renamed "MARCH-7." To probe protein expression of human axotrophin/MARCH-7, we prepared antibodies against different domains of the protein. Each antibody bound its specific target epitope with high affinity, and immunohistochemistry cross-validated target specificity. Forty-eight human tissue types were screened. Epithelial cells stained strongly, with trophoblasts having the greatest staining. In certain tissues, specific cell types were selectively positive, including neurons and neuronal progenitor cells in the hippocampus and cerebellum, endothelial sinusoids of the spleen, megakaryocytes in the bone marrow, crypt stem cells of the small intestine, and alveolar macrophages in the lung. Approximately 20% of central nervous system neuropils were positive. Notably, axotrophin/MARCH-7 has an expression profile that is distinct from that of other MARCH family members. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

  1. Resection of Perihilar Cholangiocarcinoma.

    PubMed

    Hartog, Hermien; Ijzermans, Jan N M; van Gulik, Thomas M; Groot Koerkamp, Bas

    2016-04-01

    Perihilar cholangiocarcinoma presents at the biliary and vascular junction of the hepatic hilum with a tendency to extend longitudinally into segmental bile ducts. Most patients show metastatic or unresectable disease at time of presentation or surgical exploration. In patients eligible for surgical resection, challenges are to achieve negative bile duct margins, adequate liver remnant function, and adequate portal and arterial inflow to the liver remnant. Surgical treatment is characterized by high rates of postoperative morbidity and mortality. This article reviews the various strategies and techniques, the role of staging laparoscopy, intraoperative frozen section, caudate lobectomy, and vascular reconstruction.

  2. Laparoscopic Resection of an Adrenal Schwannoma

    PubMed Central

    Konstantinos, Toutouzas G.; Panagiotis, Kekis B.; Nikolaos, Michalopoulos V.; Ioannis, Flessas; Andreas, Manouras; Geogrios, Zografos

    2012-01-01

    Background and Objectives: Schwannomas are tumors originating from Schwann cells of the peripheral nerve sheath (neurilemma) of the neuroectoderm. Rarely, schwannomas can arise from the retroperitoneum and adrenal medulla. We describe a case of a 71-y-old woman who presented with an incidentally discovered adrenal tumor. Methods: Ultrasound and computed tomography scans revealed a lesion with solid and cystic areas originating from the left adrenal gland. The patient underwent complete laparoscopic resection of the tumor and the left adrenal gland. Results: Histopathological examination and immunohistochemical staining of the excised specimen revealed a benign schwannoma measuring 5.5×5×3.7 cm. To our knowledge, few other cases of laparoscopic resection of adrenal schwannomas have been reported. Conclusion: Because preoperative diagnosis of adrenal tumors is inconclusive, complete laparoscopic excision allows for definitive diagnosis with histological evaluation and represents the treatment of choice. PMID:23484583

  3. Endoscopic resection of esthesioneuroblastoma.

    PubMed

    Gallia, Gary L; Reh, Douglas D; Lane, Andrew P; Higgins, Thomas S; Koch, Wayne; Ishii, Masaru

    2012-11-01

    Esthesioneuroblastoma, or olfactory neuroblastoma, is an uncommon malignant tumor arising in the upper nasal cavity. Surgical approaches to this and other sinonasal malignancies involving the anterior skull base have traditionally involved craniofacial resections. Over the past 10 years to 15 years, there have been advances in endoscopic approaches to skull base pathologies, including malignant tumors. In this study, we review our experience with purely endoscopic approaches to esthesioneuroblastomas. Between January 2005 and February 2012, 11 patients (seven men and four women, average age 53.3 years) with esthesioneuroblastoma were treated endoscopically. Nine patients presented with newly diagnosed disease and two were treated for tumor recurrence. The modified Kadish staging was: A, two patients (18.2%); B, two patients (18.2%); C, five patients (45.5%); and D, two patients (18.2%). All patients had a complete resection with negative intraoperative margins. Three patients had 2-deoxy-2-((18)F)fluoro-d-glucose avid neck nodes on their preoperative positron emission tomography-CT scan. These patients underwent neck dissections; two had positive neck nodes. Perioperative complications included an intraoperative hypertensive urgency and pneumocephalus in two different patients. Mean follow-up was over 28 months and all patients were free of disease. This series adds to the growing experience of purely endoscopic surgical approaches in the treatment of skull base tumors including esthesioneuroblastoma. Longer follow-up on larger numbers of patients is required to clarify the utility of purely endoscopic approaches in the management of this malignant tumor.

  4. Cultivation Versus Molecular Analysis of Banana (Musa sp.) Shoot-Tip Tissue Reveals Enormous Diversity of Normally Uncultivable Endophytic Bacteria.

    PubMed

    Thomas, Pious; Sekhar, Aparna Chandra

    2017-05-01

    The interior of plants constitutes a unique environment for microorganisms with various organisms inhabiting as endophytes. Unlike subterranean plant parts, aboveground parts are relatively less explored for endophytic microbial diversity. We employed a combination of cultivation and molecular approaches to study the endophytic bacterial diversity in banana shoot-tips. Cultivable bacteria from 20 sucker shoot-tips of cv. Grand Naine included 37 strains under 16 genera and three phyla (Proteobacteria, Actinobacteria, Firmicutes). 16S rRNA gene-ribotyping approach on 799f and 1492r PCR-amplicons to avoid plant organelle sequences was ineffective showing limited bacterial diversity. 16S rRNA metagene profiling targeting the V3-V4 hypervariable region after filtering out the chloroplast (74.2 %), mitochondrial (22.9 %), and unknown sequences (1.1 %) revealed enormous bacterial diversity. Proteobacteria formed the predominant phylum (64 %) succeeded by Firmicutes (12.1 %), Actinobacteria (9.5 %), Bacteroidetes (6.4 %), Planctomycetes, Cyanobacteria, and minor shares (<1 %) of 14 phyla including several candidate phyla besides the domain Euryarchaeota (0.2 %). Microbiome analysis of single shoot-tips through 16S rRNA V3 region profiling showed similar taxonomic richness and diversity and was less affected by plant sequence interferences. DNA extraction kit ominously influenced the phylogenetic diversity. The study has revealed vast diversity of normally uncultivable endophytic bacteria prevailing in banana shoot-tips (20 phyla, 46 classes) with about 2.6 % of the deciphered 269 genera and 1.5 % of the 656 observed species from the same source of shoot-tips attained through cultivation. The predominant genera included several agriculturally important bacteria. The study reveals an immense ecosystem of endophytic bacteria in banana shoot tissues endorsing the earlier documentation of intracellular "Cytobacts" and "Peribacts" with possible roles in plant

  5. Quantitative analysis of tissue deformation dynamics reveals three characteristic growth modes and globally aligned anisotropic tissue deformation during chick limb development.

    PubMed

    Morishita, Yoshihiro; Kuroiwa, Atsushi; Suzuki, Takayuki

    2015-05-01

    Tissue-level characterization of deformation dynamics is crucial for understanding organ morphogenetic mechanisms, especially the interhierarchical links among molecular activities, cellular behaviors and tissue/organ morphogenetic processes. Limb development is a well-studied topic in vertebrate organogenesis. Nevertheless, there is still little understanding of tissue-level deformation relative to molecular and cellular dynamics. This is mainly because live recording of detailed cell behaviors in whole tissues is technically difficult. To overcome this limitation, by applying a recently developed Bayesian approach, we here constructed tissue deformation maps for chick limb development with high precision, based on snapshot lineage tracing using dye injection. The precision of the constructed maps was validated with a clear statistical criterion. From the geometrical analysis of the map, we identified three characteristic tissue growth modes in the limb and showed that they are consistent with local growth factor activity and cell cycle length. In particular, we report that SHH signaling activity changes dynamically with developmental stage and strongly correlates with the dynamic shift in the tissue growth mode. We also found anisotropic tissue deformation along the proximal-distal axis. Morphogenetic simulation and experimental studies suggested that this directional tissue elongation, and not local growth, has the greatest impact on limb shaping. This result was supported by the novel finding that anisotropic tissue elongation along the proximal-distal axis occurs independently of cell proliferation. Our study marks a pivotal point for multi-scale system understanding in vertebrate development.

  6. 3D-printed guiding templates for improved osteosarcoma resection

    PubMed Central

    Ma, Limin; Zhou, Ye; Zhu, Ye; Lin, Zefeng; Wang, Yingjun; Zhang, Yu; Xia, Hong; Mao, Chuanbin

    2016-01-01

    Osteosarcoma resection is challenging due to the variable location of tumors and their proximity with surrounding tissues. It also carries a high risk of postoperative complications. To overcome the challenge in precise osteosarcoma resection, computer-aided design (CAD) was used to design patient-specific guiding templates for osteosarcoma resection on the basis of the computer tomography (CT) scan and magnetic resonance imaging (MRI) of the osteosarcoma of human patients. Then 3D printing technique was used to fabricate the guiding templates. The guiding templates were used to guide the osteosarcoma surgery, leading to more precise resection of the tumorous bone and the implantation of the bone implants, less blood loss, shorter operation time and reduced radiation exposure during the operation. Follow-up studies show that the patients recovered well to reach a mean Musculoskeletal Tumor Society score of 27.125. PMID:26997197

  7. 3D-printed guiding templates for improved osteosarcoma resection.

    PubMed

    Ma, Limin; Zhou, Ye; Zhu, Ye; Lin, Zefeng; Wang, Yingjun; Zhang, Yu; Xia, Hong; Mao, Chuanbin

    2016-03-21

    Osteosarcoma resection is challenging due to the variable location of tumors and their proximity with surrounding tissues. It also carries a high risk of postoperative complications. To overcome the challenge in precise osteosarcoma resection, computer-aided design (CAD) was used to design patient-specific guiding templates for osteosarcoma resection on the basis of the computer tomography (CT) scan and magnetic resonance imaging (MRI) of the osteosarcoma of human patients. Then 3D printing technique was used to fabricate the guiding templates. The guiding templates were used to guide the osteosarcoma surgery, leading to more precise resection of the tumorous bone and the implantation of the bone implants, less blood loss, shorter operation time and reduced radiation exposure during the operation. Follow-up studies show that the patients recovered well to reach a mean Musculoskeletal Tumor Society score of 27.125.

  8. 3D-printed guiding templates for improved osteosarcoma resection

    NASA Astrophysics Data System (ADS)

    Ma, Limin; Zhou, Ye; Zhu, Ye; Lin, Zefeng; Wang, Yingjun; Zhang, Yu; Xia, Hong; Mao, Chuanbin

    2016-03-01

    Osteosarcoma resection is challenging due to the variable location of tumors and their proximity with surrounding tissues. It also carries a high risk of postoperative complications. To overcome the challenge in precise osteosarcoma resection, computer-aided design (CAD) was used to design patient-specific guiding templates for osteosarcoma resection on the basis of the computer tomography (CT) scan and magnetic resonance imaging (MRI) of the osteosarcoma of human patients. Then 3D printing technique was used to fabricate the guiding templates. The guiding templates were used to guide the osteosarcoma surgery, leading to more precise resection of the tumorous bone and the implantation of the bone implants, less blood loss, shorter operation time and reduced radiation exposure during the operation. Follow-up studies show that the patients recovered well to reach a mean Musculoskeletal Tumor Society score of 27.125.

  9. Carinal resection and sleeve pneumonectomy

    PubMed Central

    2016-01-01

    Carinal resection (CR) and sleeve pneumonectomy (SP) are one of the challenging issues in thoracic surgery and performed rarely. In spite of the knowledge of the technique, the incidence of postoperative complications is higher compared to standard resections. Adequate patient selection, improved anesthetic management, surgical technique and better postoperative management might reduce the rate of postoperative morbidity and mortality. PMID:27942410

  10. Macrophage polarisation changes within the time between diagnostic biopsy and tumour resection in oral squamous cell carcinomas—an immunohistochemical study

    PubMed Central

    Weber, M; Moebius, P; Büttner-Herold, M; Amann, K; Preidl, R; Neukam, F W; Wehrhan, F

    2015-01-01

    Background: The prognosis of solid malignancies has been shown to depend on immunological parameters, such as macrophage polarisation (M1/M2). Recently, it was reported that preoperative oral surgery leads to a worsening of oral squamous cell carcinomas (OSCC) prognosis. Diagnostic incision biopsies are oral surgery procedures that might lead to healing-associated M2 macrophage polarisation with a potential negative influence on tumour biology. No studies have compared macrophage polarisation in OSCC biopsies and tumour specimens. Methods: Preoperative diagnostic incision biopsies (n=25) and tumour resection specimens (n=34) of T1/T2 OSCC were processed for immunohistochemistry to detect CD68-, CD11c-, CD163- and MRC1-positive cells. Samples were digitised using whole-slide imaging, and the expression of macrophage markers was quantitatively analysed. Results: Carcinoma tissues obtained during OSCC tumour resections showed a significantly (P<0.05) increased CD163 cell count (M2 macrophages) compared with tissues obtained during preoperative incision biopsies. Additionally, the CD163/CD68 ratio (an indicator of M2 polarisation) was significantly (P<0.05) higher in tumour resection specimens than in biopsies. Conclusions: This study revealed for the first time an increase in M2 polarisation in samples obtained during OSCC tumour resection surgery compared with preoperative incision biopsies. The biopsy-induced tissue trauma might explain the observed shift in macrophage polarisation towards the tumour-promoting M2 type and could lead to accelerated tumour progression. PMID:26110975

  11. Early Adaptation of Small Intestine After Massive Small Bowel Resection in Rats

    PubMed Central

    Chen, Jie; Qin, Zhen; Shan, Hongmei; Xiao, Yongtao; Cai, Wei

    2015-01-01

    Background: It is important that the residual bowel adapts after massive resection. The necessary intestinal adaptation is a progressive recovery from intestinal failure through increase in absorptive surface area and functional capacity and includes both morphological and functional adaptations. Objectives: The aim of this study was to investigate intestinal morphological and functional adaptations of small bowel syndrome (SBS) model rats (SBS1W) 7 days after bowel resection. Materials and Methods: Male sprague–dawley rats (n = 20/group) underwent either a 75% proximal small bowel resection (SBS1W group) or a control operation (control group). Markers of morphological adaptation were revealed by TEM analysis of H&E-stained tissue samples. The intestinal barrier condition was assessed by BT, and sIgA concentration in intestinal mucus was measured by ELISA. Contractility and the slow wave rhythm of the entire intestinal remnant were measured and recorded. Results: The SBS1W group experienced more weight loss than control group and had a clearly different intestinal morphology as revealed in TEM images. Compared with control rats, the SBS1W group had a lower sIgA concentration in intestinal mucus and higher BT to lymph nodes (70% vs 40%; level I), portal blood (40% vs 10%; level II), and peripheral blood (60% vs 30%; level III). Disorder of spontaneous rhythmic contraction, irregular amplitude, and slow frequency were detected in the SBS1W group by a muscle strips test. Similarly, the slow wave of the entire intestinal remnant in the SBS1W group was irregular and uncoordinated. Conclusions: The finding of intestinal adaptation following massive SBR in SBS1W rats provides more understanding of the mechanisms of progressive recovery from the intestinal failure that underlies SBS. The mechanical, chemical, immunological, and biological barriers were all impaired at 7 days following bowel resection, indicating that the SBS model rats were still in the intestinal

  12. Analysis of gelsolin expression pattern in developing chicken embryo reveals high GSN expression level in tissues of neural crest origin.

    PubMed

    Mazur, Antonina Joanna; Morosan-Puopolo, Gabriela; Makowiecka, Aleksandra; Malicka-Błaszkiewicz, Maria; Nowak, Dorota; Brand-Saberi, Beate

    2016-01-01

    Gelsolin is one of the most intensively studied actin-binding proteins. However, in the literature comprehensive studies of GSN expression during development have not been performed yet in all model organisms. In zebrafish, gelsolin is a dorsalizing factor that modulates bone morphogenetic proteins signaling pathways, whereas knockout of the gelsolin coding gene, GSN is not lethal in murine model. To study the role of gelsolin in development of higher vertebrates, it is crucial to estimate GSN expression pattern during development. Here, we examined GSN expression in the developing chicken embryo. We applied numerous methods to track GSN expression in developing embryos at mRNA and protein level. We noted a characteristic GSN expression pattern. Although GSN transcripts were present in several cell types starting from early developmental stages, a relatively high GSN expression was observed in eye, brain vesicles, midbrain, neural tube, heart tube, and splanchnic mesoderm. In older embryos, we observed a high GSN expression in the cranial ganglia and dorsal root ganglia. A detailed analysis of 10-day-old chicken embryos revealed high amounts of gelsolin especially within the head region: in the olfactory and optic systems, meninges, nerves, muscles, presumptive pituitary gland, and pericytes, but not oligodendrocytes in the brain. Obtained results suggest that GSN is expressed at high levels in some tissues of ectodermal origin including all neural crest derivatives. Additionally, we describe that silencing of GSN expression in brain vesicles leads to altered morphology of the mesencephalon. This implies gelsolin is crucial for chicken brain development.

  13. Chest wall reconstruction after extended resection

    PubMed Central

    Seder, Christopher W.

    2016-01-01

    Extensive chest wall resection and reconstruction is a challenging procedure that requires a multidisciplinary approach, including input from thoracic surgeons, plastic surgeons, neurosurgeons, and radiation oncologists. The primary goals of any chest wall reconstruction is to obliterate dead space, restore chest wall rigidity, preserve pulmonary mechanics, protect intrathoracic organs, provide soft tissue coverage, minimize deformity, and allow patients to receive adjuvant radiotherapy. Successful chest wall reconstruction requires the re-establishment of skeletal stability to prevent chest wall hernias, avoids thoracoplasty-like contraction of the operated side, protects underlying viscera, and maintain a cosmetically-acceptable appearance. After skeletal stability is established, full tissue coverage can be achieved using direct closure, skin grafts, local advancement flaps, pedicled myocutaneous flaps, or free flaps. This review examines the indications for chest wall reconstruction and describes techniques for establishment of chest wall rigidity and soft tissue coverage. PMID:27942408

  14. Clinical outcome of transthoracic esophagectomy with thoracic duct resection

    PubMed Central

    Matsuda, Satoru; Takeuchi, Hiroya; Kawakubo, Hirofumi; Shimada, Ayako; Fukuda, Kazumasa; Nakamura, Rieko; Takahashi, Tsunehiro; Wada, Norihito; Kameyama, Kaori; Kitagawa, Yuko

    2016-01-01

    Abstract The number of dissected lymph nodes (LNs), surgical outcomes, and postoperative recurrence-free survival (RFS) were compared between thoracic duct (TD)-preserved and TD-resected groups. The distribution of metastasis in LNs around TD (TDLN) was reviewed. Transthoracic esophagectomy (TTE) with TD resection for esophageal cancer patients has been one of the standard procedures. Because the adipose tissue surrounding the TD contains LNs, TD resection might be necessary for radical LN dissection. However, few studies have investigated the oncological outcome of TTE with TD resection. Two hundred fifty-six consecutive patients who underwent TTE between 2004 and 2015 were retrospectively reviewed and classified into TD-preserved or TD-resected groups. The number of dissected LNs for each LN station and surgical outcomes were compared. RFS was analyzed in 155 patients who underwent TTE before December 2012. Since 2013, the TDLN number was prospectively examined, independent of the regional LNs (n = 72). Of these, the TDLN number for each location (TDLN-Ut/Mt/Lt) was investigated and the correlation between TDLN metastasis and clinicopathological factors was analyzed. The TD was preserved in 89 patients and resected in 167 patients. Patients with TD resection showed significant advanced stage. There was no significant difference in the incidence of postoperative complications, including pneumonia, anastomotic leakage, and chylothorax. The number of dissected mediastinal LNs was significantly increased in the TD-resected group. The 5-year RFS rate of cStage I patients was 67.3% in the TD-preserved group against 90.3% in the TD-resected group, showing a tendency towards RFS extension that did not quite reach statistical significance (P = 0.055). The mean TDLN-Ut/Mt/Lt numbers were 0.89/0.56/0.44, respectively. Eight of 72 (11%) patients displayed TDLN metastasis. Metastatic TDLNs were observed on the same or cranial level of the primary lesion in 7 of 8 patients

  15. Computer-Assisted Resection and Reconstruction of Pelvic Tumor Sarcoma

    PubMed Central

    Docquier, Pierre-Louis; Paul, Laurent; Cartiaux, Olivier; Delloye, Christian; Banse, Xavier

    2010-01-01

    Pelvic sarcoma is associated with a relatively poor prognosis, due to the difficulty in obtaining an adequate surgical margin given the complex pelvic anatomy. Magnetic resonance imaging and computerized tomography allow valuable surgical resection planning, but intraoperative localization remains hazardous. Surgical navigation systems could be of great benefit in surgical oncology, especially in difficult tumor location; however, no commercial surgical oncology software is currently available. A customized navigation software was developed and used to perform a synovial sarcoma resection and allograft reconstruction. The software permitted preoperative planning with defined target planes and intraoperative navigation with a free-hand saw blade. The allograft was cut according to the same planes. Histological examination revealed tumor-free resection margins. Allograft fitting to the pelvis of the patient was excellent and allowed stable osteosynthesis. We believe this to be the first case of combined computer-assisted tumor resection and reconstruction with an allograft. PMID:21127723

  16. Computer-assisted resection and reconstruction of pelvic tumor sarcoma.

    PubMed

    Docquier, Pierre-Louis; Paul, Laurent; Cartiaux, Olivier; Delloye, Christian; Banse, Xavier

    2010-01-01

    Pelvic sarcoma is associated with a relatively poor prognosis, due to the difficulty in obtaining an adequate surgical margin given the complex pelvic anatomy. Magnetic resonance imaging and computerized tomography allow valuable surgical resection planning, but intraoperative localization remains hazardous. Surgical navigation systems could be of great benefit in surgical oncology, especially in difficult tumor location; however, no commercial surgical oncology software is currently available. A customized navigation software was developed and used to perform a synovial sarcoma resection and allograft reconstruction. The software permitted preoperative planning with defined target planes and intraoperative navigation with a free-hand saw blade. The allograft was cut according to the same planes. Histological examination revealed tumor-free resection margins. Allograft fitting to the pelvis of the patient was excellent and allowed stable osteosynthesis. We believe this to be the first case of combined computer-assisted tumor resection and reconstruction with an allograft.

  17. Deep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver Failure and Tissue Evidence of Impaired Energy Metabolism

    PubMed Central

    Valencia, C. Alexander; Wang, Xinjian; Wang, Jin; Peters, Anna; Simmons, Julia R.; Moran, Molly C.; Mathur, Abhinav; Husami, Ammar; Qian, Yaping; Sheridan, Rachel; Bove, Kevin E.; Witte, David; Huang, Taosheng; Miethke, Alexander G.

    2016-01-01

    Background & Aims The etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism. Methods Twelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver samples were available for histological, ultrastructural, molecular and biochemical analysis. Results A customized next-generation sequencing panel for 26 genes associated with mitochondrial and fatty acid oxidation defects revealed mutations and sequence variants in five subjects. Variants involved the genes ACAD9, POLG, POLG2, DGUOK, and RRM2B; the latter not previously reported in subjects with ALF. The explanted livers of the patients with heterozygous, truncating insertion mutations in RRM2B showed patchy micro- and macrovesicular steatosis, decreased mitochondrial DNA (mtDNA) content <30% of controls, and reduced respiratory chain complex activity; both patients had good post-transplant outcome. One infant with severe lactic acidosis was found to carry two heterozygous variants in ACAD9, which was associated with isolated complex I deficiency and diffuse hypergranular hepatocytes. The two subjects with heterozygous variants of unknown clinical significance in POLG and DGUOK developed ALF following drug exposure. Their hepatocytes displayed abnormal mitochondria by electron microscopy. Conclusion Targeted next generation sequencing and correlation with histological, ultrastructural and functional studies on liver tissue in children with elevated lactate/pyruvate ratio expand the spectrum of genes associated with pediatric ALF. PMID:27483465

  18. Transurethral resection of the prostate

    MedlinePlus

    TURP; Prostate resection - transurethral ... used to remove the inside part of your prostate gland using electricity. ... if you have benign prostatic hyperplasia ( BPH ). The prostate gland often grows larger as men get older. ...

  19. Gene expression profiles reveal effect of a high-fat diet on the development of white and brown adipose tissues.

    PubMed

    Kim, Hyeng-Soo; Ryoo, Zae Young; Choi, Sang Un; Lee, Sanggyu

    2015-07-01

    Because of the recent discovery of brown adipose tissues tissue in adult humans, brown adipose tissues have garnered additional attention. Many studies have attempted to transform the precursor cells within the white adipocyte cultures to Brite (brown-in-white) cells by using genomic modification or pharmacological activation in order to determine the therapeutic effect of obesity. However, genome-scale analysis of the genetic factors governing the development of white and brown adipose tissues remains incomplete. In order to identify the key genes that regulate the development of white and brown adipose tissues in mice, a transcriptome analysis was performed on the adipose tissues. Network analysis of differentially expressed genes indicated that Trim30 and Ucp3 play pivotal roles in energy balance and glucose homeostasis. In addition, it was discovered that identical biological processes and pathways in the white and brown adipose tissues might be regulated by different genes. Trim30 and Ucp3 might be used as genetic markers to precisely represent the stage of obesity during the early and late stages of adipose tissue development, respectively. These results may provide a stepping-stone for future obesity-related studies.

  20. Unusual presentation of a complication after pulmonary wedge resection for coccidioma.

    PubMed

    Leduc, François; Thipphavong, Seng; Matzinger, Fred; Dennie, Carole; Sundaresan, Sudhir

    2009-12-01

    We report an unusual presentation of a complication after pulmonary wedge resection. A patient with a history of pulmonary wedge resection for coccidioma presented postoperatively with dyspnea and severe hypoxemia. Cerebral infarctions were diagnosed less than 1 year later. Cardiac magnetic resonance imaging and pulmonary angiogram revealed a pulmonary arteriovenous fistula. Surgical resection of the pulmonary arteriovenous fistula led to improved oxygen saturation and discontinuation of home oxygen.

  1. The long-term results of resection and multiple resections in Crohn's disease.

    PubMed

    Krupnick, A S; Morris, J B

    2000-01-01

    Crohn's disease is a panenteric, transmural inflammatory disease of unknown origin. Although primarily managed medically, 70% to 90% of patients will require surgical intervention. Surgery for small bowel Crohn's is usually necessary for unrelenting stenotic complications of the disease. Fistula, abscess, and perforation can also necessitate surgical intervention. Most patients benefit from resection or strictureplasty with an improved quality of life and remission of disease, but recurrence is common and 33% to 82% of patients will need a second operation, and 22% to 33% will require more than two resections. Short-bowel syndrome is unavoidable in a small percentage of Crohn's patients because of recurrent resection of affected small bowel and inflammatory destruction of the remaining mucosa. Although previously a lethal and unrelenting disease with death caused by malnutrition, patients with short-bowel syndrome today can lead productive lives with maintenance on total parenteral nutrition (TPN). This lifestyle, however, does not come without a price. Severe TPN-related complications, such as sepsis of indwelling central venous catheters and liver failure, do occur. Future developments will focus on more powerful and effective anti-inflammatory medication specifically targeting the immune mechanisms responsible for Crohn's disease. Successful medical management of the disease will alleviate the need for surgical resection and reduce the frequency of short-bowel syndrome. Improving the efficacy of immunosuppression and the understanding of tolerance induction should increase the safety and applicability of small-bowel transplant for those with short gut. Tissue engineering offers the potential to avoid immunosuppression altogether and supplement intestinal length using the patient's own tissues.

  2. Semi-quantitative immunohistochemical detection of 5-hydroxymethyl-cytosine reveals conservation of its tissue distribution between amphibians and mammals.

    PubMed

    Almeida, Rimple D; Sottile, Virginie; Loose, Matthew; De Sousa, Paul A; Johnson, Andrew D; Ruzov, Alexey

    2012-02-01

    5-Hydroxymethyl-cytosine (5-hmC) is a form of modified cytosine, which has recently attracted a considerable attention due to its potential role in transcriptional regulation. According to several reports 5-hydroxymethyl-cytosine distribution is tissue-specific in mammals. Thus, 5-hmC is enriched in embryonic cell populations and in adult neuronal tissue. Here, we describe a novel method of semi-quantitative immunohistochemical detection of 5-hmC and utilize it to assess the levels of this modification in amphibian tissues. We show that, similar to mammalian embryos, 5-hmC is enriched in axolotl tadpoles compared with adult tissues. Our data demonstrate that 5-hmC distribution is tissue-specific in amphibians, and that strong 5-hmC enrichment in neuronal cells is conserved between amphibians and mammals. In addition, we identify 5-hmC-enriched cell populations that are distributed in amphibian skin and connective tissue in a mosaic manner. Our results illustrate that immunochemistry can be successfully used not only for spatial identification of cells enriched with 5-hmC, but also for the semi-quantitative assessment of the levels of this epigenetic modification in single cells of different tissues.

  3. Novel bioactivity of phosvitin in connective tissue and bone organogenesis revealed by live calvarial bone organ culture models.

    PubMed

    Liu, Jess; Czernick, Drew; Lin, Shih-Chun; Alasmari, Abeer; Serge, Dibart; Salih, Erdjan

    2013-09-01

    Egg yolk phosvitin is one of the most highly phosphorylated extracellular matrix proteins known in nature with unique physico-chemical properties deemed to be critical during ex-vivo egg embryo development. We have utilized our unique live mouse calvarial bone organ culture models under conditions which dissociates the two bone remodeling stages, viz., resorption by osteoclasts and formation by osteoblasts, to highlight important and to date unknown critical biological functions of egg phosvitin. In our resorption model live bone cultures were grown in the absence of ascorbate and were stimulated by parathyroid hormone (PTH) to undergo rapid osteoclast formation/differentiation with bone resorption. In this resorption model native phosvitin potently inhibited PTH-induced osteoclastic bone resorption with simultaneous new osteoid/bone formation in the absence of ascorbate (vitamin C). These surprising and critical observations were extended using the bone formation model in the absence of ascorbate and in the presence of phosvitin which supported the above results. The results were corroborated by analyses for calcium release or uptake, tartrate-resistant acid phosphatase activity (marker for osteoclasts), alkaline phosphatase activity (marker for osteoblasts), collagen and hydroxyproline composition, and histological and quantitative histomorphometric evaluations. The data revealed that the discovered bioactivity of phosvitin mirrors that of ascorbate during collagen synthesis and the formation of new osteoid/bone. Complementing those studies use of the synthetic collagen peptide analog and cultured calvarial osteoblasts in conjunction with mass spectrometric analysis provided results that augmented the bone organ culture work and confirmed the capacity of phosvitin to stimulate differentiation of osteoblasts, collagen synthesis, hydroxyproline formation, and biomineralization. There are striking implications and interrelationships of this affect that relates to

  4. Chronic laminitis: strategic hoof wall resection.

    PubMed

    Rucker, Amy

    2010-04-01

    In the chronic-laminitic foot, severe soft-tissue compression and compromised circulation can result in osteitis and sepsis at the margin of the distal phalanx. Resultant inflammation and sepsis may cause the coronary corium to swell, drain, or separate from the hoof capsule, usually within 8 weeks of laminitis onset. Slow-onset cases of soft-tissue impingement can develop secondary to distal phalanx displacement due to lack of wall attachment. With either presentation, partial upper wall resection is required to reverse compression and vascular impingement by the hoof capsule. If the pathology is not overwhelming, the area reepithelializes and grows attached tubular horn. Firm bandaging and restricted exercise until tubular horn has regrown enhances recovery and the return of a strong hoof.

  5. PHF11 promotes DSB resection, ATR signaling, and HR.

    PubMed

    Gong, Yi; Handa, Naofumi; Kowalczykowski, Stephen C; de Lange, Titia

    2017-01-01

    Resection of double-strand breaks (DSBs) plays a critical role in their detection and appropriate repair. The 3' ssDNA protrusion formed through resection activates the ATR-dependent DNA damage response (DDR) and is required for DSB repair by homologous recombination (HR). Here we report that PHF11 (plant homeodomain finger 11) encodes a previously unknown DDR factor involved in 5' end resection, ATR signaling, and HR. PHF11 was identified based on its association with deprotected telomeres and localized to sites of DNA damage in S phase. Depletion of PHF11 diminished the ATR signaling response to telomere dysfunction and genome-wide DNA damage, reduced end resection at sites of DNA damage, resulted in compromised HR and misrejoining of S-phase DSBs, and increased the sensitivity to DNA-damaging agents. PHF11 interacted with the ssDNA-binding protein RPA and was found in a complex with several nucleases, including the 5' dsDNA exonuclease EXO1. Biochemical experiments demonstrated that PHF11 stimulates EXO1 by overcoming its inhibition by RPA, suggesting that PHF11 acts (in part) by promoting 5' end resection at RPA-bound sites of DNA damage. These findings reveal a role for PHF11 in DSB resection, DNA damage signaling, and DSB repair.

  6. PHF11 promotes DSB resection, ATR signaling, and HR

    PubMed Central

    Gong, Yi; Handa, Naofumi; Kowalczykowski, Stephen C.; de Lange, Titia

    2017-01-01

    Resection of double-strand breaks (DSBs) plays a critical role in their detection and appropriate repair. The 3′ ssDNA protrusion formed through resection activates the ATR-dependent DNA damage response (DDR) and is required for DSB repair by homologous recombination (HR). Here we report that PHF11 (plant homeodomain finger 11) encodes a previously unknown DDR factor involved in 5′ end resection, ATR signaling, and HR. PHF11 was identified based on its association with deprotected telomeres and localized to sites of DNA damage in S phase. Depletion of PHF11 diminished the ATR signaling response to telomere dysfunction and genome-wide DNA damage, reduced end resection at sites of DNA damage, resulted in compromised HR and misrejoining of S-phase DSBs, and increased the sensitivity to DNA-damaging agents. PHF11 interacted with the ssDNA-binding protein RPA and was found in a complex with several nucleases, including the 5′ dsDNA exonuclease EXO1. Biochemical experiments demonstrated that PHF11 stimulates EXO1 by overcoming its inhibition by RPA, suggesting that PHF11 acts (in part) by promoting 5′ end resection at RPA-bound sites of DNA damage. These findings reveal a role for PHF11 in DSB resection, DNA damage signaling, and DSB repair. PMID:28115467

  7. Resection Interposition Arthroplasty for Failed Distal Ulna Resections

    PubMed Central

    Papatheodorou, Loukia K.; Rubright, James H.; Kokkalis, Zinon T.; Sotereanos, Dean G.

    2013-01-01

    The major complications of distal ulna resection, the Darrach procedure, are radioulnar impingement and instability. High failure rates have been reported despite published modifications of the Darrach procedure. Several surgical techniques have been developed to treat this difficult problem and to mitigate the symptoms associated with painful convergence and impingement. No technique has demonstrated clinical superiority. Recently, implant arthroplasty of the distal ulna has been endorsed as an option for the management of the symptomatic patient with a failed distal ulna resection. However, there are concerns for implant longevity, especially in young, active adults. Resection interposition arthroplasty relies on interposition of an Achilles tendon allograft between the distal radius and the resected distal ulna. Although this technique does not restore normal mechanics of the distal radioulnar joint, it can prevent painful convergence of the radius on the ulna. Achilles allograft interposition arthroplasty is a safe and highly effective alternative for failed distal ulna resections, especially for young, active patients, in whom an implant or alternative procedure may not be appropriate. PMID:24436784

  8. Biodistribution of cisplatin revealed by imaging mass cytometry identifies extensive collagen binding in tumor and normal tissues

    PubMed Central

    Chang, Qing; Ornatsky, Olga I.; Siddiqui, Iram; Straus, Rita; Baranov, Vladimir I.; Hedley, David W.

    2016-01-01

    Imaging mass cytometry was used for direct visualization of platinum localization in tissue sections from tumor and normal tissues of cisplatin-treated mice bearing pancreas cancer patient-derived xenografts. This recently-developed technology enabled simultaneous detection of multiple markers to define cell lineage, DNA damage response, cell proliferation and functional state, providing a highly detailed view of drug incorporation in tumor and normal tissues at the cellular level. A striking and unanticipated finding was the extensive binding of platinum to collagen fibers in both tumor and normal mouse tissues. Time course experiments indicated the slow release of stroma-bound platinum, although it is currently unclear if released platinum retains biological activity. Imaging mass cytometry offers a unique window into the in vivo effects of platinum compounds, and it is likely that this can be extended into the clinic in order to optimize the use of this important class of agent. PMID:27812005

  9. Comparative transcriptomics and gene expression in larval tiger salamander (Ambystoma tigrinum) gill and lung tissues as revealed by pyrosequencing.

    PubMed

    Eo, Soo Hyung; Doyle, Jacqueline M; Hale, Matthew C; Marra, Nicholas J; Ruhl, Joseph D; DeWoody, J Andrew

    2012-01-25

    Biologists are beginning to unravel the complexities of gene expression in model organisms by studying the transcriptome, the complement of genes that are transcribed in a given tissue. It is unclear, however, if findings from model systems apply to non-model organisms because of environmental effects on gene expression. Furthermore, there have been few efforts to quantify how transcriptome or gene expression varies across individuals and across tissues in natural environments. Herein, we describe transcriptomic profiling of gene expression in lung and gill tissue of three larval tiger salamanders. We do so with a hierarchical experimental design that captures variation in expression among genes, among tissues, and among individuals. Using 454 pyrosequencing, we produced high-quality sequence data of 59 megabases and assembled ~200,000 reads into 19,501 contigs. These contigs BLASTed to 3,599 transcripts, of which 721 were expressed in both tissues, 1,668 were unique to gill, and 1,210 unique to lung. Our data showed tissue-specific patterns in gene expression level with variation among transcripts and individuals. We identified genes and gene ontology terms related to respiration and compared their relative expression levels between gill and lung tissues. We also found evidence of exogenous genes associated with larval salamanders, and we identified ~1400 potential molecular markers (microsatellites and single nucleotide polymorphisms) that are associated with expressed genes. Given the tissue-specific differences we observed in transcriptomes, these data reinforce the idea that changes in gene expression serve as a primary mechanism underlying phenotypic plasticity.

  10. Evaluation of Conoscopic Holography for Estimating Tumor Resection Cavities in Model-Based Image-Guided Neurosurgery

    PubMed Central

    Sun, Kay; Pheiffer, Thomas S.; Rucker, D. Caleb; Sills, Allen K.; Thompson, Reid C.; Miga, Michael I.

    2014-01-01

    Surgical navigation relies on accurately mapping the intraoperative state of the patient to models derived from preoperative images. In image-guided neurosurgery, soft tissue deformations are common and have been shown to compromise the accuracy of guidance systems. In lieu of whole-brain intraoperative imaging, some advocate the use of intraoperatively acquired sparse data from laser-range scans, ultrasound imaging, or stereo reconstruction coupled with a computational model to drive subsurface deformations. Some authors have reported on compensating for brain sag, swelling, retraction, and the application of pharmaceuticals such as mannitol with these models. To date, strategies for modeling tissue resection have been limited. In this paper, we report our experiences with a novel digitization approach, called a conoprobe, to document tissue resection cavities and assess the impact of resection on model-based guidance systems. Specifically, the conoprobe was used to digitize the interior of the resection cavity during eight brain tumor resection surgeries and then compared against model prediction results of tumor locations. We should note that no effort was made to incorporate resection into the model but rather the objective was to determine if measurement was possible to study the impact on modeling tissue resection. In addition, the digitized resection cavity was compared with early postoperative MRI scans to determine whether these scans can further inform tissue resection. The results demonstrate benefit in model correction despite not having resection explicitly modeled. However, results also indicate the challenge that resection provides for model-correction approaches. With respect to the digitization technology, it is clear that the conoprobe provides important real-time data regarding resection and adds another dimension to our noncontact instrumentation framework for soft-tissue deformation compensation in guidance systems. PMID:24845293

  11. Large-scale atlas of microarray data reveals the distinct expression landscape of different tissues in Arabidopsis

    SciTech Connect

    He, Fei; Maslov, Sergei; Yoo, Shinjae; Wang, Daifeng; Kumari, Sunita; Gerstein, Mark; Ware, Doreen

    2016-05-25

    Here, transcriptome datasets from thousands of samples of the model plant Arabidopsis thaliana have been collectively generated by multiple individual labs. Although integration and meta-analysis of these samples has become routine in the plant research community, it is often hampered by the lack of metadata or differences in annotation styles by different labs. In this study, we carefully selected and integrated 6,057 Arabidopsis microarray expression samples from 304 experiments deposited to NCBI GEO. Metadata such as tissue type, growth condition, and developmental stage were manually curated for each sample. We then studied global expression landscape of the integrated dataset and found that samples of the same tissue tend to be more similar to each other than to samples of other tissues, even in different growth conditions or developmental stages. Root has the most distinct transcriptome compared to aerial tissues, but the transcriptome of cultured root is more similar to those of aerial tissues as the former samples lost their cellular identity. Using a simple computational classification method, we showed that the tissue type of a sample can be successfully predicted based on its expression profile, opening the door for automatic metadata extraction and facilitating re-use of plant transcriptome data. As a proof of principle we applied our automated annotation pipeline to 708 RNA-seq samples from public repositories and verified accuracy of our predictions with samples’ metadata provided by authors.

  12. Large-scale atlas of microarray data reveals the distinct expression landscape of different tissues in Arabidopsis

    DOE PAGES

    He, Fei; Maslov, Sergei; Yoo, Shinjae; ...

    2016-05-25

    Here, transcriptome datasets from thousands of samples of the model plant Arabidopsis thaliana have been collectively generated by multiple individual labs. Although integration and meta-analysis of these samples has become routine in the plant research community, it is often hampered by the lack of metadata or differences in annotation styles by different labs. In this study, we carefully selected and integrated 6,057 Arabidopsis microarray expression samples from 304 experiments deposited to NCBI GEO. Metadata such as tissue type, growth condition, and developmental stage were manually curated for each sample. We then studied global expression landscape of the integrated dataset andmore » found that samples of the same tissue tend to be more similar to each other than to samples of other tissues, even in different growth conditions or developmental stages. Root has the most distinct transcriptome compared to aerial tissues, but the transcriptome of cultured root is more similar to those of aerial tissues as the former samples lost their cellular identity. Using a simple computational classification method, we showed that the tissue type of a sample can be successfully predicted based on its expression profile, opening the door for automatic metadata extraction and facilitating re-use of plant transcriptome data. As a proof of principle we applied our automated annotation pipeline to 708 RNA-seq samples from public repositories and verified accuracy of our predictions with samples’ metadata provided by authors.« less

  13. Incomplete resection rate of cold snare polypectomy: a prospective single-arm observational study.

    PubMed

    Matsuura, Noriko; Takeuchi, Yoji; Yamashina, Takeshi; Ito, Takashi; Aoi, Kenji; Nagai, Kengo; Kanesaka, Takashi; Matsui, Fumi; Fujii, Mototsugu; Akasaka, Tomofumi; Hanaoka, Noboru; Higashino, Koji; Tomita, Yasuhiko; Ito, Yuri; Ishihara, Ryu; Iishi, Hiroyasu; Uedo, Noriya

    2017-03-01

    Background and study aims Cold snare polypectomy (CSP) is considered to be safe for the removal of subcentimeter colorectal polyps. This study aimed to determine the rate of incomplete CSP resection for subcentimeter neoplastic polyps at our center. Patients and methods Patients with small or diminutive adenomas (diameter 1 - 9 mm) were recruited to undergo CSP until no polyp was visible. After CSP, a 1 - 3 mm margin around the resection site was removed using endoscopic mucosal resection. The polyps and resection site marginal specimens were microscopically evaluated. Incomplete resection was defined as the presence of neoplastic tissue in the marginal specimen. We also calculated the frequency at which the polyp lateral margins could be assessed for completeness of resection. Results A total of 307 subcentimeter neoplastic polyps were removed from 120 patients. The incomplete resection rate was 3.9 % (95 % confidence interval [CI] 1.7 % - 6.1 %); incomplete resection was not associated with polyp size, location, morphology, or operator experience. The polyp lateral margins could not be assessed adequately for 206 polyps (67.1 %). Interobserver agreement between incomplete resection and lateral polyp margins that were inadequate for assessment was poor (κ = 0.029, 95 %CI 0 - 0.04). Female sex was an independent risk factor for incomplete resection (odds ratio 4.41, 95 %CI 1.26 - 15.48; P  = 0.02). Conclusions At our center, CSP resection was associated with a moderate rate of incomplete resection, which was not associated with polyp characteristics. However, adequate evaluation of resection may not be routinely possible using the lateral margin from subcentimeter polyps that were removed using CSP.Trial registered at University Hospital Medical Information Network (UMIN 000010879).

  14. Prognostic signature of protocadherin 10 methylation in curatively resected pathological stage I non-small-cell lung cancer

    PubMed Central

    Harada, Hiroaki; Miyamoto, Kazuaki; Yamashita, Yoshinori; Taniyama, Kiyomi; Mihara, Kazuko; Nishimura, Mitsuki; Okada, Morihito

    2015-01-01

    Although curative resection is the current treatment of choice for localized non-small-cell lung cancer (NSCLC), patients show a wide spectrum of survival even after complete resection of pathological stage I NSCLC. Thus, identifying molecular biomarkers that help to accurately select patients at high risk of relapse is an important key to improving the treatment strategy. The purpose of this study was to evaluate the prognostic signature of protocadherin 10 (PCDH10) promoter methylation in curatively resected pathological stage I NSCLC. Using methylation-specific polymerase chain reaction assays, methylation of PCDH10 promoter was assessed in cancer tissues of 109 patients who underwent curative resection of pathological stage I NSCLC. Associations between PCDH10 methylation status and disease outcome was analyzed. PCDH10 promoter methylation was detected in 46/109 patients (42.2%). Patients with methylated PCDH10 showed significantly worse recurrence-free, overall, and disease-specific survival compared with those without methylation (P < 0.0001, P = 0.0004, P = 0.0002, respectively). Multivariate Cox proportional hazard regression analysis revealed that adjusted hazard ratios of methylated PCDH10 were 5.159 for recurrence-free, 1.817 for overall, and 5.478 for disease-specific survival (P = 0.0005, P = 0.1475, P = 0.0109, respectively). The pattern of recurrence was not significantly different between patients with and without PCDH10 methylation (P = 0.5074). PCDH10 methylation is a potential biomarker that predicts a poor prognosis after curative resection of pathological stage I NSCLC. Assessment of PCDH10 methylation status might assist in patient stratification for determining an appropriate adjuvant treatment and follow-up strategy. PMID:26276761

  15. Oligonucleotide microarray analysis reveals dysregulation of energy-related metabolism in insulin-sensitive tissues of type 2 diabetes patients.

    PubMed

    Wang, M; Wang, X C; Zhao, L; Zhang, Y; Yao, L L; Lin, Y; Peng, Y D; Hu, R M

    2014-06-17

    Impaired insulin action within skeletal muscle, adipose tissue, and the liver is an important characteristic of type 2 diabetes (T2D). In order to identify common underlying defects in insulin-sensitive tissues that may be involved in the pathogenesis of T2D, the gene expression profiles of skeletal muscle, visceral adipose tissue, and liver from autopsy donors with or without T2D were examined using oligonucleotide microarrays and quantitative reverse transcriptase-PCR. Compared with controls, 691 genes were commonly dysregulated in these three insulin-sensitive tissues of humans with T2D. These co-expressed genes were enriched within the mitochondrion, with suggested involvement in energy metabolic processes such as glycolysis and gluconeogenesis, fatty acid beta oxidative, tricarboxylic acid cycle, and electron transport. Genes related to energy metabolism were mostly downregulated in diabetic skeletal muscle and visceral adipose tissue, while they were upregulated in the diabetic liver. This observed dysregulation in energy-related metabolism may be the underlying factor leading to the molecular mechanisms responsible for the insulin resistance of patients with T2D.

  16. Simulation of brain tumor resection in image-guided neurosurgery

    NASA Astrophysics Data System (ADS)

    Fan, Xiaoyao; Ji, Songbai; Fontaine, Kathryn; Hartov, Alex; Roberts, David; Paulsen, Keith

    2011-03-01

    Preoperative magnetic resonance images are typically used for neuronavigation in image-guided neurosurgery. However, intraoperative brain deformation (e.g., as a result of gravitation, loss of cerebrospinal fluid, retraction, resection, etc.) significantly degrades the accuracy in image guidance, and must be compensated for in order to maintain sufficient accuracy for navigation. Biomechanical finite element models are effective techniques that assimilate intraoperative data and compute whole-brain deformation from which to generate model-updated MR images (uMR) to improve accuracy in intraoperative guidance. To date, most studies have focused on early surgical stages (i.e., after craniotomy and durotomy), whereas simulation of more complex events at later surgical stages has remained to be a challenge using biomechanical models. We have developed a method to simulate partial or complete tumor resection that incorporates intraoperative volumetric ultrasound (US) and stereovision (SV), and the resulting whole-brain deformation was used to generate uMR. The 3D ultrasound and stereovision systems are complimentary to each other because they capture features deeper in the brain beneath the craniotomy and at the exposed cortical surface, respectively. In this paper, we illustrate the application of the proposed method to simulate brain tumor resection at three temporally distinct surgical stages throughout a clinical surgery case using sparse displacement data obtained from both the US and SV systems. We demonstrate that our technique is feasible to produce uMR that agrees well with intraoperative US and SV images after dural opening, after partial tumor resection, and after complete tumor resection. Currently, the computational cost to simulate tumor resection can be up to 30 min because of the need for re-meshing and the trial-and-error approach to refine the amount of tissue resection. However, this approach introduces minimal interruption to the surgical workflow

  17. Recurrence of Hypertrophic Abductor Digiti Minimi Muscle of the Foot After Subtotal Resection.

    PubMed

    Schmauss, Daniel; Harder, Yves; Machens, Hans-Guenther; Lohmeyer, Joern Andreas

    2016-01-01

    Soft tissue tumors of the foot are rare, and the diagnosis is often difficult. Surgery is indicated if pain, discomfort, or functional impairment is present or to rule out malignancy. We present the case of a 14-year-old female with a painless swelling at the lateral aspect of her right foot. After radiologic imaging, including ultrasonography and magnetic resonance imaging (MRI), we performed a subtotal resection of the abductor digiti minimi muscle, preserving its motor nerve. Four months later, recurrence of the soft tissue mass was observed. MRI revealed hypertrophy of the small muscles of the foot, including the abductor digiti minimi, quadratus plantae, and flexor digiti minimi brevis. Functional impairment resulted in complete excision of the remnant abductor digiti minimi muscle and partial excision of the flexor digiti minimi brevis muscle another 7 months later. Twelve months after the secondary surgery, neither clinical nor radiologic signs of a second recurrence were found. At the last follow-up visit, the patient was satisfied with the contour of her foot and not hindered at all during sporting activities. Our findings demonstrate that subtotal resection of a bulky muscle, preserving its motor nerve, can result in reactive hypertrophy of the remnant muscle part. The patient must be informed that partial excision of an innervated muscle could result in reactive hypertrophy and must be contrasted with radical muscle excision that might be more likely to result in functional impairment.

  18. Multi-tissue analyses reveal limited inter-annual and seasonal variation in mercury exposure in an Antarctic penguin community.

    PubMed

    Brasso, Rebecka L; Polito, Michael J; Emslie, Steven D

    2014-10-01

    Inter-annual variation in tissue mercury concentrations in birds can result from annual changes in the bioavailability of mercury or shifts in dietary composition and/or trophic level. We investigated potential annual variability in mercury dynamics in the Antarctic marine food web using Pygoscelis penguins as biomonitors. Eggshell membrane, chick down, and adult feathers were collected from three species of sympatrically breeding Pygoscelis penguins during the austral summers of 2006/2007-2010/2011. To evaluate the hypothesis that mercury concentrations in penguins exhibit significant inter-annual variation and to determine the potential source of such variation (dietary or environmental), we compared tissue mercury concentrations with trophic levels as indicated by δ(15)N values from all species and tissues. Overall, no inter-annual variation in mercury was observed in adult feathers suggesting that mercury exposure, on an annual scale, was consistent for Pygoscelis penguins. However, when examining tissues that reflected more discrete time periods (chick down and eggshell membrane) relative to adult feathers, we found some evidence of inter-annual variation in mercury exposure during penguins' pre-breeding and chick rearing periods. Evidence of inter-annual variation in penguin trophic level was also limited suggesting that foraging ecology and environmental factors related to the bioavailability of mercury may provide more explanatory power for mercury exposure compared to trophic level alone. Even so, the variable strength of relationships observed between trophic level and tissue mercury concentrations across and within Pygoscelis penguin species suggest that caution is required when selecting appropriate species and tissue combinations for environmental biomonitoring studies in Antarctica.

  19. Large Scale Gene Expression Meta-Analysis Reveals Tissue-Specific, Sex-Biased Gene Expression in Humans

    PubMed Central

    Mayne, Benjamin T.; Bianco-Miotto, Tina; Buckberry, Sam; Breen, James; Clifton, Vicki; Shoubridge, Cheryl; Roberts, Claire T.

    2016-01-01

    The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analyzed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes), followed by the heart (375 genes), kidney (224 genes), colon (218 genes), and thyroid (163 genes). More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs, and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases. PMID:27790248

  20. Novel Approaches Reveal that Toxoplasma gondii Bradyzoites within Tissue Cysts Are Dynamic and Replicating Entities In Vivo

    PubMed Central

    Watts, Elizabeth; Zhao, Yihua; Dhara, Animesh; Eller, Becca; Patwardhan, Abhijit

    2015-01-01

    ABSTRACT Despite their critical role in chronic toxoplasmosis, the biology of Toxoplasma gondii bradyzoites is poorly understood. In an attempt to address this gap, we optimized approaches to purify tissue cysts and analyzed the replicative potential of bradyzoites within these cysts. In order to quantify individual bradyzoites within tissue cysts, we have developed imaging software, BradyCount 1.0, that allows the rapid establishment of bradyzoite burdens within imaged optical sections of purified tissue cysts. While in general larger tissue cysts contain more bradyzoites, their relative “occupancy” was typically lower than that of smaller cysts, resulting in a lower packing density. The packing density permits a direct measure of how bradyzoites develop within cysts, allowing for comparisons across progression of the chronic phase. In order to capture bradyzoite endodyogeny, we exploited the differential intensity of TgIMC3, an inner membrane complex protein that intensely labels newly formed/forming daughters within bradyzoites and decays over time in the absence of further division. To our surprise, we were able to capture not only sporadic and asynchronous division but also synchronous replication of all bradyzoites within mature tissue cysts. Furthermore, the time-dependent decay of TgIMC3 intensity was exploited to gain insights into the temporal patterns of bradyzoite replication in vivo. Despite the fact that bradyzoites are considered replicatively dormant, we find evidence for cyclical, episodic bradyzoite growth within tissue cysts in vivo. These findings directly challenge the prevailing notion of bradyzoites as dormant nonreplicative entities in chronic toxoplasmosis and have implications on our understanding of this enigmatic and clinically important life cycle stage. PMID:26350965

  1. Liver resection using a water jet.

    PubMed

    Une, Y; Uchino, J; Horie, T; Sato, Y; Ogasawara, K; Kakita, A; Sano, F

    1989-01-01

    The water-jet method has been used during hepatic resection. The instrument cuts the hepatic tissue with the high pressure of the fine water flow, while the exposed elastic intrahepatic vessels are spared injury. A comparative study on the water-jet method with the previously employed conventional methods was undertaken. Hepatic resections were performed on 35 patients using the water-jet method. Cirrhosis of the liver was associated with 10 of the 24 patients with hepatocellular carcinoma. An ordinary saline solution was used as the jet, which was projected at a pressure of between 12 kg/cm2 and 20 kg/cm2 through a 0.15/mm-diameter nozzle. A higher jet pressure was needed to cut the fibrotic hepatic parenchyma. In the case of normal liver, the intrahepatic vessels of more than 0.2 mm were well preserved. In most of the cases, the loss of blood when cutting the hepatic parenchyma can be easily reduced with a jet pressure of 15-16 kg/cm2, thus preserving the fine vessels more than 0.2 mm in diameter without injury. When the same pressure was applied in the cutting of a cirrhotic liver, it took much longer time compared to that of a non-cirrhotic normal liver parenchyma. The cut surface was smooth compared to that after using CUSA, although its disadvantages lie in the formation of air bubbles, which obscure the operative field. The controlled projection of a jet of water under optimal pressure may ensure a safe hepatic resection of both normal and cirrhotic livers. Furthermore, because of its uncomplicated form, a wide range of applications can be expected, while the lower cost will also expedite its large-scale use for economic reasons.

  2. Safe transanal tumor resection using a harmonic scalpel.

    PubMed

    Inoue, Yuji; Ohki, Takeshi; Nakagawa, Ryousuke; Yamamoto, Masakazu

    2014-01-01

    We performed a safe and simple transanal tumor resection involving total layer resection using a harmonic scalpel as a resecting device. Here we report the results of our experience with this technique between 2005 and 2011. This study involved 32 patients who underwent transanal tumor resection using a harmonic scalpel. The subjects comprised 18 men and 14 women ranging in age from 34 to 87 years (mean: 64.5 years). The tumors measured 8 to 70 mm (mean: 31 mm) in diameter. The operation took 7 to 86 minutes (mean: 29 minutes), and the amount of bleeding was 0 to 165 mL (mean: 16.2 mL). There was no intraoperative blood loss that necessitated hemostatic procedures. Histopathologically, the lesions included hyperplastic polyp in 1 case, adenoma in 9, carcinoma in situ in 7, submucosal invasive cancer in 6, muscularis propria cancer in 4, carcinoid in 1, malignant lymphoma in 1, gastrointestinal stromal tumor in 1, mucosal prolapsed syndrome in 1, and mucosa-associated lymphoid tissue lymphoma in 1. With our technique, en bloc resection was achieved in all patients, and the use of a harmonic scalpel enabled us to complete the operation within 30 minutes, on average, without intraoperative bleeding.

  3. Visualizing the neutrophil response to sterile tissue injury in mouse dermis reveals a three-phase cascade of events.

    PubMed

    Ng, Lai Guan; Qin, Jim S; Roediger, Ben; Wang, Yilin; Jain, Rohit; Cavanagh, Lois L; Smith, Adrian L; Jones, Cheryl A; de Veer, Michael; Grimbaldeston, Michele A; Meeusen, Els N; Weninger, Wolfgang

    2011-10-01

    Neutrophil granulocytes traffic into sites of organ injury in which they may not only participate in tissue repair and pathogen clearance but may also contribute to collateral cell damage through the release of noxious mediators. The dynamics and mechanisms of neutrophil migration in the extravascular space toward loci of tissue damage are not well understood. Here, we have used intravital multi-photon microscopy to dissect the behavior of neutrophils in response to tissue injury in the dermis of mice. We found that, following confined physical injury, initially rare scouting neutrophils migrated in a directional manner toward the damage focus. This was followed by the attraction of waves of additional neutrophils, and finally stabilization of the neutrophil cluster around the injury. Although neutrophil migration in the steady state and during the scouting phase depended on pertussis toxin-sensitive signals, the amplification phase was sensitive to interference with the cyclic adenosine diphosphate ribose pathway. We finally demonstrated that neutrophil scouts also transit through the non-inflamed dermis, suggesting immunosurveillance function by these cells. Together, our data unravel a three-step cascade of events that mediates the specific accumulation of neutrophils at sites of sterile tissue injury in the interstitial space.

  4. An atlas of bovine gene expression reveals novel distinctive tissue characteristics and evidence for improving genome annotation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background A comprehensive transcriptome survey, or gene atlas, provides information essential for a complete understanding of the genomic biology of an organism. We present an atlas of RNA abundance for 92 adult, juvenile and fetal cattle tissues and three cattle cell lines. Results The Bovine Gene...

  5. Differential adaptive responses to 1- or 2-day fasting in various mouse tissues revealed by quantitative PCR analysis

    PubMed Central

    Yamamoto, Junya; Kamata, Shotaro; Miura, Asumi; Nagata, Tomoko; Kainuma, Ryo; Ishii, Isao

    2015-01-01

    Dietary or caloric restriction confers various clinical benefits. Short-term fasting of mice is a common experimental procedure that may involve systemic metabolic remodeling, which may significantly affect experimental outputs. This study evaluated adaptive cellular responses after 1- or 2-day fasting in 13 mouse tissues by quantitative PCR using 15 marker primer sets for the activation of ubiquitin–proteasome (Atrogin-1 and MuRF1), autophagy–lysosome (LC3b, p62 and Lamp2), amino acid response (Asns, Trib3, Herpud1, xCT, and Chop), Nrf2-mediated antioxidant (HO-1 and Gsta1), and amino acid transport (Slc38a2, Slc7a5, and Slc7a1) systems. Differential activation profiles obtained in seven highly (thymus, liver, spleen, and small intestine) or mildly (stomach, kidney, and colon) atrophied tissues as well as in six non-atrophied tissues (brain, eye, lung, heart, skeletal muscle, and testis) suggested tissue-specific active metabolic remodeling. PMID:25973363

  6. Spatio-temporal profiling of Filamin A RNA-editing reveals ADAR preferences and high editing levels outside neuronal tissues

    PubMed Central

    Stulić, Maja; Jantsch, Michael F

    2013-01-01

    RNA editing by ADARs can change the coding potential of protein-coding mRNAs. So far, this type of RNA editing has mainly been shown to affect RNAs expressed in the nervous system with much lower editing levels being observed in other tissues. The actin crosslinking proteins filamin α and filamin β are widely expressed in most tissues. The mRNAs encoding either protein are edited at the same position leading to a conserved Q to R exchange in both proteins. Using bar-coded next generation sequencing, we show that editing of filamin α is most abundant in the gastrointestinal tract and only to a lesser extent in the nervous system. Using knockout mice, we show that ADARB1 (ADAR2) is responsible for the majority of FLNA editing, while ADAR1 can edit filamin α mRNA in some tissues quite efficiently. Interestingly, editing levels of filamin α and β do not follow the same trend across tissues, suggesting a substrate-specific regulation of editing. PMID:24025532

  7. ATR-FTIR spectroscopy reveals genomic loci regulating the tissue response in high fat diet fed BXD recombinant inbred mouse strains

    PubMed Central

    2013-01-01

    Background Obesity-associated organ-specific pathological states can be ensued from the dysregulation of the functions of the adipose tissues, liver and muscle. However, the influence of genetic differences underlying gross-compositional differences in these tissues is largely unknown. In the present study, the analytical method of ATR-FTIR spectroscopy has been combined with a genetic approach to identify genetic differences responsible for phenotypic alterations in adipose, liver and muscle tissues. Results Mice from 29 BXD recombinant inbred mouse strains were put on high fat diet and gross-compositional changes in adipose, liver and muscle tissues were measured by ATR-FTIR spectroscopy. The analysis of genotype-phenotype correlations revealed significant quantitative trait loci (QTL) on chromosome 12 for the content of fat and collagen, collagen integrity, and the lipid to protein ratio in adipose tissue and on chromosome 17 for lipid to protein ratio in liver. Using gene expression and sequence information, we suggest Rsad2 (viperin) and Colec11 (collectin-11) on chromosome 12 as potential quantitative trait candidate genes. Rsad2 may act as a modulator of lipid droplet contents and lipid biosynthesis; Colec11 might play a role in apoptopic cell clearance and maintenance of adipose tissue. An increased level of Rsad2 transcripts in adipose tissue of DBA/2J compared to C57BL/6J mice suggests a cis-acting genetic variant leading to differential gene activation. Conclusion The results demonstrate that the analytical method of ATR-FTIR spectroscopy effectively contributed to decompose the macromolecular composition of tissues that accumulate fat and to link this information with genetic determinants. The candidate genes in the QTL regions may contribute to obesity-related diseases in humans, in particular if the results can be verified in a bigger BXD cohort. PMID:23758785

  8. Local resection of ampullary tumors.

    PubMed

    Meneghetti, Adam T; Safadi, Bassem; Stewart, Lygia; Way, Lawrence W

    2005-12-01

    There is no consensus on the appropriateness of local resection for ampullary tumors, because malignant recurrence of what were thought to be benign tumors has been reported. This study examined the role of local resection in the management of ampullary tumors. Thirty patients (mean age 66 years) had transduodenal local resections performed at UCSF-Moffitt Hospital or the San Francisco VA Medical Center (February, 1992 to March, 2004). Mean follow-up time was 5.8 years. Preoperative biopsies (obtained in all patients) showed 18 adenomas, four adenomas with dysplasia, five adenomas with atypia, one adenoma with dysplasia and focal adenocarcinoma, and two tumors seen on endoscopy, whose biopsies showed only duodenal mucosa. In comparison with the final pathology findings, the results of frozen section examinations for malignancy in 20 patients, during the operation, were false-negative in three cases. The final pathologic diagnosis was 23 villous adenomas, six adenocarcinomas, and one paraganglioma. On preoperative biopsies, all patients who had high-grade dysplasia and one of five patients with atypia turned out to have invasive adenocarcinoma when the entire specimen was examined postoperatively. Two (33%) adenocarcinomas recurred at a mean of 4 years; both had negative margins at the initial resection. Among the 23 adenomas, three (13%) recurred (all as adenomas) at a mean of 3.2 years; in only one of these cases was the margin positive at the time of resection. Tumor size did not influence recurrence rate. Ampullary tumors with high-grade dysplasia on preoperative biopsy should be treated by pancreaticoduodenectomy because they usually harbor malignancy. Recurrence is too common and unpredictable after local resection of malignant lesions for this to be considered an acceptable alternative to pancreaticoduodenectomy. Ampullary adenomas can be resected locally with good results, but the recurrence rate was 13%, so endoscopic surveillance is indicated

  9. Water-fat MRI in a hibernator reveals seasonal growth of white and brown adipose tissue without cold exposure.

    PubMed

    MacCannell, Amanda; Sinclair, Kevin; Friesen-Waldner, Lannette; McKenzie, Charles A; Staples, James F

    2017-03-21

    Obligate hibernators, such as ground squirrels, display circannual patterns which persist even under constant laboratory conditions, suggesting that they are regulated by endogenous rhythms. Brown adipose tissue (BAT) is important for thermogenesis during periodic arousals from hibernation when core body temperature rises spontaneously from 5 to 37 °C. In most small eutherians BAT growth requires several weeks of cold exposure. We hypothesized that in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus), a hibernator, BAT growth is regulated, in part, by an endogenous rhythm and we predicted that this growth would precede the hibernation season without cold exposure. We tested this prediction using repeated water-fat magnetic resonance imaging over a year, including the hibernation season. Thoracic BAT depots increased in volume from spring through autumn even though animals were housed at ~22 °C. Subsequent cold exposure (5 °C) enlarged the thoracic BAT further. The fat fraction of this tissue fell significantly during the period of peak growth, indicating relative increases in non-triglyceride components, perhaps mitochondria or vasculature. We also found that the proportion of the body consisting of white adipose tissue (WAT) increased steadily from spring through autumn, and fell throughout hibernation, mirroring changes in body mass. Unlike BAT, WAT fat fractions remained constant (near 90%) throughout the year. Future studies will evaluate the significance of photoperiod and cold exposure on the growth of these tissues. We also found tissue with a fat fraction characteristic of BAT in the head near the eyes, a potentially novel discovery that requires further confirmation.

  10. Transcatheter aortic valve replacement: transapical resection of the aortic valve in vivo.

    PubMed

    Bombien Quaden, René; Leester-Schaedel, Monika; Lozonschi, Lucian; Lutter, Georg

    2012-09-01

    The resection of pulmonary valves has already been demonstrated in an experimental beating-heart model. The aim of this study was to analyse the transapical laser-assisted resection of aortic valves in an in vivo porcine model in a non-beating heart. The resection was performed in a porcine model (n = 10) using a Thullium:YAG laser. After establishing a standard extracorporeal circulatory support, the aortic valve isolation chamber (AVIC) system was inserted transapically. The resection of the aortic leaflets was carried out step-by-step in the arrested heart. The AVIC implantation, the resection process, and the gross anatomy of intracardiac lesions were analysed. The procedure for installing the AVIC took 5.8 ± 1.5 min. A sealed chamber was achieved in 9/10 cases. The resection of the valves was performed in 8/10 and completed in 7/10 cases. The resection took, on average, 7.4 ± 2.7 min/cusp. In 9/10 cases, the sealing was sufficient. Gross anatomy and histological analysis demonstrated only superficial damage to the surrounding tissue. In this study, the in vivo on-pump isolation of the left ventricular outflow tract and the laser resection of the native aortic valve could be demonstrated successfully. Nevertheless, this model is the next step towards a beating-heart resection of the aortic valve using the isolation chamber.

  11. Resection margins in carcinoma of the head of the pancreas. Implications for radiation therapy.

    PubMed Central

    Willett, C G; Lewandrowski, K; Warshaw, A L; Efird, J; Compton, C C

    1993-01-01

    A retrospective review of the pathology and clinical course of 72 patients undergoing resection of carcinoma of the head of the pancreas was undertaken to identify the frequency of tumor involvement at standard surgical transection margins (stomach, duodenum, pancreas, and bile duct) as well as the peripancreatic soft tissue margin and the potential clinical significance of these findings. Of 72 patients undergoing resection, 37 patients (51%) were found to have tumor extension to the surgical margins. The most commonly involved margin was peripancreatic soft tissue (27 patients) followed by pancreatic transection line (14 patients) and bile duct transection line (4 patients). For 37 patients with tumor present at a resection margin, there were no survivors beyond 41 months. No difference in survival or local control was seen between 14 patients receiving postoperative radiation therapy and 5-fluorouracil (5-FU) compared with 23 patients not receiving additional treatment. In contrast, the 5-year actuarial survival and local control of 35 patients undergoing resection without tumor invasion to a resection margin was 22% and 43%, respectively. The 5-year survival and local control of 16 patients receiving adjuvant radiation therapy and 5-FU was 29% and 42%, respectively, whereas these figures were 18% and 31% for 19 patients not receiving adjuvant therapy (p > 0.10). Because residual local tumor after resection is common, preoperative radiation therapy may be beneficial in this disease. It should minimize the risk of dissemination during operative manipulation and facilitate a curative resection by promoting tumor regression. Because local failure rates approach 60% after resection and adjuvant therapy even in cases having clear resection margins, intraoperative radiation therapy to the tumor bed at the time of resection also might be considered. Protocols evaluating the feasibility and efficacy of preoperative radiation therapy and resection with intraoperative

  12. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    SciTech Connect

    Bujak, Emil; Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah; Neri, Dario

    2014-09-10

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  13. Avian Soft Tissue Surgery.

    PubMed

    Guzman, David Sanchez-Migallon

    2016-01-01

    Basic surgical instrumentation for avian soft tissue surgery includes soft tissue retractors, microsurgical instrumentation, surgical loupes, and head-mounted lights. Hemostasis is fundamental during the surgical procedures. The indications, approach, and complications associated with soft tissue surgeries of the integumentary (digit constriction repair, feather cyst excision, cranial wound repair, sternal wound repair, uropygial gland excision), gastrointestinal (ingluviotomy, crop biopsy, crop burn repair, celiotomy, coelomic hernia and pseudohernia repair, proventriculotomy, ventriculotomy, enterotomy, intestinal resection and anastomosis, cloacoplasty, cloacopexy), respiratory (rhinolith removal, sinusotomy, tracheotomy, tracheal resection and anastomosis, tracheostomy, pneumonectomy) and reproductive (ovocentesis, ovariectomy, salpingohysterectomy, cesarean section, orchidectomy, vasectomy, phallectomy) systems are reviewed.

  14. Giant abdominal osteosarcoma causing intestinal obstruction treated with resection and adjuvant chemotherapy

    PubMed Central

    Diamantis, Alexandros; Christodoulidis, Grigorios; Vasdeki, Dionysia; Karasavvidou, Foteini; Margonis, Evangelos; Tepetes, Konstantinos

    2017-01-01

    Extraskeletal osteosarcoma (ESOS) is an uncommon tumor that accounts for 1% of all soft tissue sarcomas and 4% of all osteosarcomas. Its presentation may be atypical, while pain has been described as the most common symptom. Radiological findings include a large mass in the soft-tissues with massive calcifications, but no attachment to the adjacent bone or periosteum. We present the case of a 73-year-old gentle man who presented with a palpable, tender abdominal mass and symptoms of bowel obstruction. Computer tomography images revealed a large space-occupying heterogeneous, hyper dense soft tissue mass involving the small intestine. Explorative laparotomy revealed a large mass in the upper mesenteric root of the small intestine, measuring 22 cm × 12 cm × 10 cm in close proximity with the cecum, which was the cause of the bowel obstruction. Pathology confirmed the diagnosis of an ESOS. ESOS is an uncommon malignant soft tissue tumor with poor prognosis and a 5-year survival rate of less than 37%. Regional recurrence and distant metastasis to lungs, regional lymph nodes and liver can occur within the first three years of diagnosis in a high rate (45% and 65% respectively). Wide surgical resection of the mass followed by adjuvant chemotherapy or radiotherapy has been the treatment of choice. PMID:28289512

  15. The interaction of asbestos and iron in lung tissue revealed by synchrotron-based scanning X-ray microscopy

    PubMed Central

    Pascolo, Lorella; Gianoncelli, Alessandra; Schneider, Giulia; Salomé, Murielle; Schneider, Manuela; Calligaro, Carla; Kiskinova, Maya; Melato, Mauro; Rizzardi, Clara

    2013-01-01

    Asbestos is a potent carcinogen associated with malignant mesothelioma and lung cancer but its carcinogenic mechanisms are still poorly understood. Asbestos toxicity is ascribed to its particular physico-chemical characteristics, and one of them is the presence of and ability to adsorb iron, which may cause an alteration of iron homeostasis in the tissue. This observational study reports a combination of advanced synchrotron-based X-ray imaging and micro-spectroscopic methods that provide correlative morphological and chemical information for shedding light on iron mobilization features during asbestos permanence in lung tissue. The results show that the processes responsible for the unusual distribution of iron at different stages of interaction with the fibres also involve calcium, phosphorus and magnesium. It has been confirmed that the dominant iron form present in asbestos bodies is ferritin, while the concurrent presence of haematite suggests alteration of iron chemistry during asbestos body permanence. PMID:23350030

  16. Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts

    PubMed Central

    Kang, Wenjing; Bang-Berthelsen, Claus Heiner; Holm, Anja; Houben, Anna J.S.; Müller, Anne Holt; Thymann, Thomas; Pociot, Flemming; Estivill, Xavier; Friedländer, Marc R.

    2017-01-01

    miRNAs are small 22-nucleotide RNAs that can post-transcriptionally regulate gene expression. It has been proposed that dietary plant miRNAs can enter the human bloodstream and regulate host transcripts; however, these findings have been widely disputed. We here conduct the first comprehensive meta-study in the field, surveying the presence and abundances of cross-species miRNAs (xenomiRs) in 824 sequencing data sets from various human tissues and body fluids. We find that xenomiRs are commonly present in tissues (17%) and body fluids (69%); however, the abundances are low, comprising 0.001% of host human miRNA counts. Further, we do not detect a significant enrichment of xenomiRs in sequencing data originating from tissues and body fluids that are exposed to dietary intake (such as liver). Likewise, there is no significant depletion of xenomiRs in tissues and body fluids that are relatively separated from the main bloodstream (such as brain and cerebro-spinal fluids). Interestingly, the majority (81%) of body fluid xenomiRs stem from rodents, which are a rare human dietary contribution but common laboratory animals. Body fluid samples from the same studies tend to group together when clustered by xenomiR compositions, suggesting technical batch effects. Last, we performed carefully designed and controlled animal feeding studies, in which we detected no transfer of plant miRNAs into rat blood, or bovine milk sequences into piglet blood. In summary, our comprehensive computational and experimental results indicate that xenomiRs originate from technical artifacts rather than dietary intake. PMID:28062594

  17. Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues

    PubMed Central

    Koski, Anniina; Bramante, Simona; Kipar, Anja; Oksanen, Minna; Juhila, Juuso; Vassilev, Lotta; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli

    2015-01-01

    In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients. PMID:26156245

  18. [Liver resection by water jet].

    PubMed

    Horie, T

    1989-01-01

    Major problem in resecting liver parenchyma is how to control the bleeding. Recently, resection of the liver by water jet has been reported. So, experimental and clinical studies were performed to investigate the usefulness of the water jet equipment. Ten pigs weighing around 17kg were used. The optimal pressure to resect the porcine liver was 7 to 15kg/cm2. By 4 weeks the cut surface was covered with fibrous capsule. Portal angiography showed no abnormality in the resected area. The water jet was also used in 30 human operations. The optimal pressure was 12 to 18kg/cm2 for non cirrhotic liver and 15 to 20kg/cm2 for cirrhotic liver. The surface immediately after jet cutting was more smooth than that of CUSA and histologically there was slight bleeding and necrosis. The volume of blood loss during dissection was not different between water jet group and CUSA group. No significant changes were found in the laboratory data. These results suggest that water jet is as useful as CUSA for cutting the liver parenchyma.

  19. Transurethral resection of the prostate - discharge

    MedlinePlus

    TURP - discharge; Prostate resection - transurethral - discharge ... You had transurethral resection of the prostate (TURP) surgery to treat an enlarged prostate. Your surgeon inserted a tube-like tool called a cystoscope (or endoscope) through your urethra ( ...

  20. Painful Spastic Hip Dislocation: Proximal Femoral Resection

    PubMed Central

    Albiñana, Javier; Gonzalez-Moran, Gaspar

    2002-01-01

    The dislocated hip in a non-ambulatory child with spastic paresis tends to be a painful interference to sleep, sitting upright, and perineal care. Proximal femoral resection-interposition arthroplasty is one method of treatment for this condition. We reviewed eight hips, two bilateral cases, with a mean follow-up of 30 months. Clinical improvement was observed in all except one case, with respect to pain relief and sitting tolerance. Some proximal migration was observed in three cases, despite routine post-operative skeletal traction in all cases and careful soft tissue interposition. One case showed significant heterotopic ossification which restricted prolonged sitting. This patient needed some occasional medication for pain. PMID:12180614

  1. Ganglioside Profiling of the Human Retina: Comparison with Other Ocular Structures, Brain and Plasma Reveals Tissue Specificities

    PubMed Central

    Sibille, Estelle; Berdeaux, Olivier; Martine, Lucy; Bron, Alain M.; Creuzot-Garcher, Catherine P.; He, Zhiguo; Thuret, Gilles; Bretillon, Lionel; Masson, Elodie A. Y.

    2016-01-01

    Gangliosides make a wide family of glycosphingolipids, highly heterogeneous in both the ceramide moiety and the oligosaccharide chain. While ubiquitously expressed in mammalian tissues, they are particularly abundant in the brain and the peripheral nervous system. Gangliosides are known to play a crucial role in the development, maintenance and functional integrity of the nervous system. However, the expression and roles of gangliosides in the retina, although often considered as a window on the brain, has been far less studied. We performed an in-depth analysis of gangliosides of the human retina, especially using powerful LC/MS methods. We compared the pattern of ganglioside classes and ceramide molecular species of this tissue with other ocular structures and with brain and plasma in elderly human individuals. About a hundred of ganglioside molecular species among 15 distinct classes were detected illustrating the huge structural diversity of these compounds. The retina exhibited a very diverse ganglioside profile and shared several common features with the brain (prominence of tetraosylgangliosides, abundance of d20:1 long chain base and 18:0 fatty acid…). However, the retina stood out with the specific expression of GD3, GT3 and AcGT3, which further presented a peculiar molecular species distribution. The unique ganglioside pattern we observed in the human retina suggests that these ganglioside species play a specific role in the structure and function of this tissue. This lipidomic study, by highlighting retina specific ganglioside species, opens up novel research directions for a better understanding of the biological role of gangliosides in the retina. PMID:27997589

  2. Computational modeling reveals that a combination of chemotaxis and differential adhesion leads to robust cell sorting during tissue patterning.

    PubMed

    Tan, Rui Zhen; Chiam, Keng-Hwee

    2014-01-01

    Robust tissue patterning is crucial to many processes during development. The "French Flag" model of patterning, whereby naïve cells in a gradient of diffusible morphogen signal adopt different fates due to exposure to different amounts of morphogen concentration, has been the most widely proposed model for tissue patterning. However, recently, using time-lapse experiments, cell sorting has been found to be an alternative model for tissue patterning in the zebrafish neural tube. But it remains unclear what the sorting mechanism is. In this article, we used computational modeling to show that two mechanisms, chemotaxis and differential adhesion, are needed for robust cell sorting. We assessed the performance of each of the two mechanisms by quantifying the fraction of correct sorting, the fraction of stable clusters formed after correct sorting, the time needed to achieve correct sorting, and the size variations of the cells having different fates. We found that chemotaxis and differential adhesion confer different advantages to the sorting process. Chemotaxis leads to high fraction of correct sorting as individual cells will either migrate towards or away from the source depending on its cell type. However after the cells have sorted correctly, there is no interaction among cells of the same type to stabilize the sorted boundaries, leading to cell clusters that are unstable. On the other hand, differential adhesion results in low fraction of correct clusters that are more stable. In the absence of morphogen gradient noise, a combination of both chemotaxis and differential adhesion yields cell sorting that is both accurate and robust. However, in the presence of gradient noise, the simple combination of chemotaxis and differential adhesion is insufficient for cell sorting; instead, chemotaxis coupled with delayed differential adhesion is required to yield optimal sorting.

  3. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis.

    PubMed

    Sato, Ryo; Nakano, Teppei; Hosonaga, Mari; Sampetrean, Oltea; Harigai, Ritsuko; Sasaki, Takashi; Koya, Ikuko; Okano, Hideyuki; Kudoh, Jun; Saya, Hideyuki; Arima, Yoshimi

    2017-01-01

    Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non-small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  4. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

    PubMed Central

    Hosonaga, Mari; Koya, Ikuko

    2017-01-01

    Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients. PMID:28210624

  5. Transcriptional profiling of peripheral lymphoid tissue reveals genes and networks linked to SSBP/1 scrapie pathology in sheep.

    PubMed

    Gossner, Anton; Roupaka, Sofia; Foster, Jim; Hunter, Nora; Hopkins, John

    2011-12-15

    Transmissible spongiform encephalopathies (TSEs) are slow and progressive neurodegenerative diseases of humans and animals. The major target organ for all TSEs is the brain but some TSE agents are associated with prior accumulation within the peripheral lymphoid system. Many studies have examined the effects of scrapie infection on the expression of central nervous system (CNS) genes, but this study examines the progression of scrapie pathology in the peripheral lymphoid system and how scrapie infection affects the transcriptome of the lymph nodes and spleen. Infection of sheep with SSBP/1 scrapie resulted in PrP(Sc) deposition in the draining prescapular lymph node (PSLN) by 25 days post infection (dpi) in VRQ/VRQ genotype sheep and 75 dpi in tonsils and spleen. Progression of PrP(Sc) deposition in VRQ/ARR animals was 25 dpi later in the PSLN and 250 dpi later in spleen. Microarray analysis of 75 dpi tissues from VRQ/VRQ sheep identified 52 genes in PSLN and 37 genes in spleen cells that showed significant difference (P ≤ 0.05) between scrapie-infected and mock-infected animals. Transcriptional pathway analysis highlighted immunological disease, cell death and neurological disease as the biological pathways associated with scrapie pathogenesis in the peripheral lymphoid system. PrP(Sc) accumulation of lymphoid tissue resulted in the repression of genes linked to inflammation and oxidative stress, and the up-regulation of genes related to apoptosis.

  6. Extended multiplexing of TMT labeling reveals age and high fat diet specific proteome changes in mouse epididymal adipose tissue.

    PubMed

    Plubell, Deanna L; Wilmarth, Phillip A; Zhao, Yuqi; Fenton, Alexandra M; Minnier, Jessica; Reddy, Ashok P; Klimek, John; Yang, Xia; David, Larry L; Pamir, Nathalie

    2017-03-21

    The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with TMT labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low vs. high fat diets. The peripheral metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet and advancing age, with long-term high fat diet exposure being the worst. In response to short-term high fat diet, 43 proteins representing lipid metabolism (e.g., AACS, ACOX1, ACLY) and red-ox pathways (e.g., CPD2, CYP2E, SOD3) were significantly altered (FDR < 10%). Long-term high fat diet significantly altered 55 proteins associated with immune response (e.g., IGTB2, IFIT3, LGALS1) and rennin angiotensin system (e.g. ENPEP, CMA1, CPA3, ANPEP). Age-related changes on low fat diet significantly altered only 18 proteins representing mainly urea cycle (e.g., OTC, ARG1, CPS1), and amino acid biosynthesis (e.g., GMT, AKR1C6). Surprisingly, high fat diet driven age-related changes culminated with alterations in 155 proteins involving primarily the urea cycle (e.g., ARG1, CPS1), immune response/complement activation (e.g., C3, C4b, C8, C9, CFB, CFH, FGA), extracellular remodeling (e.g., EFEMP1, FBN1, FBN2, LTBP4, FERMT2, ECM1, EMILIN2, ITIH3) and apoptosis (e.g., YAP1, HIP1, NDRG1, PRKCD, MUL1) pathways. Using our adipose tissue tailored approach we have identified both age-related and high fat diet specific proteomic signatures highlighting a pronounced involvement of arginine metabolism in response to advancing age, and branched

  7. Synchrotron soft X-ray imaging and fluorescence microscopy reveal novel features of asbestos body morphology and composition in human lung tissues

    PubMed Central

    2011-01-01

    Background Occupational or environmental exposure to asbestos fibres is associated with pleural and parenchymal lung diseases. A histopathologic hallmark of exposure to asbestos is the presence in lung parenchyma of the so-called asbestos bodies. They are the final product of biomineralization processes resulting in deposition of endogenous iron and organic matter (mainly proteins) around the inhaled asbestos fibres. For shedding light on the formation mechanisms of asbestos bodies it is of fundamental importance to characterize at the same length scales not only their structural morphology and chemical composition but also to correlate them to the possible alterations in the local composition of the surrounding tissues. Here we report the first correlative morphological and chemical characterization of untreated paraffinated histological lung tissue samples with asbestos bodies by means of soft X-ray imaging and X-Ray Fluorescence (XRF) microscopy, which reveals new features in the elemental lateral distribution. Results The X-ray absorption and phase contrast images and the simultaneously monitored XRF maps of tissue samples have revealed the location, distribution and elemental composition of asbestos bodies and associated nanometric structures. The observed specific morphology and differences in the local Si, Fe, O and Mg content provide distinct fingerprints characteristic for the core asbestos fibre and the ferruginous body. The highest Si content is found in the asbestos fibre, while the shell and ferruginous bodies are characterized by strongly increased content of Mg, Fe and O compared to the adjacent tissue. The XRF and SEM-EDX analyses of the extracted asbestos bodies confirmed an enhanced Mg deposition in the organic asbestos coating. Conclusions The present report demonstrates the potential of the advanced synchrotron-based X-ray imaging and microspectroscopy techniques for studying the response of the lung tissue to the presence of asbestos fibres

  8. Listening to speech recruits specific tongue motor synergies as revealed by transcranial magnetic stimulation and tissue-Doppler ultrasound imaging.

    PubMed

    D'Ausilio, A; Maffongelli, L; Bartoli, E; Campanella, M; Ferrari, E; Berry, J; Fadiga, L

    2014-01-01

    The activation of listener's motor system during speech processing was first demonstrated by the enhancement of electromyographic tongue potentials as evoked by single-pulse transcranial magnetic stimulation (TMS) over tongue motor cortex. This technique is, however, technically challenging and enables only a rather coarse measurement of this motor mirroring. Here, we applied TMS to listeners' tongue motor area in association with ultrasound tissue Doppler imaging to describe fine-grained tongue kinematic synergies evoked by passive listening to speech. Subjects listened to syllables requiring different patterns of dorso-ventral and antero-posterior movements (/ki/, /ko/, /ti/, /to/). Results show that passive listening to speech sounds evokes a pattern of motor synergies mirroring those occurring during speech production. Moreover, mirror motor synergies were more evident in those subjects showing good performances in discriminating speech in noise demonstrating a role of the speech-related mirror system in feed-forward processing the speaker's ongoing motor plan.

  9. Organization and evolution of brain lipidome revealed by large-scale analysis of human, chimpanzee, macaque, and mouse tissues.

    PubMed

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng; Liu, Xiling; Xiong, Jieyi; Sugimoto, Masahiro; Tomita, Masaru; Pääbo, Svante; Sherwood, Chet C; Hof, Patrick R; Ely, John J; Li, Yan; Steinhauser, Dirk; Willmitzer, Lothar; Giavalisco, Patrick; Khaitovich, Philipp

    2015-02-18

    Lipids are prominent components of the nervous system. Here we performed a large-scale mass spectrometry-based analysis of the lipid composition of three brain regions as well as kidney and skeletal muscle of humans, chimpanzees, rhesus macaques, and mice. The human brain shows the most distinct lipid composition: 76% of 5,713 lipid compounds examined in our study are either enriched or depleted in the human brain. Concentration levels of lipids enriched in the brain evolve approximately four times faster among primates compared with lipids characteristic of non-neural tissues and show further acceleration of change in human neocortical regions but not in the cerebellum. Human-specific concentration changes are supported by human-specific expression changes for corresponding enzymes. These results provide the first insights into the role of lipids in human brain evolution.

  10. Integrative mRNA-microRNA analyses reveal novel interactions related to insulin sensitivity in human adipose tissue.

    PubMed

    Kirby, Tyler J; Walton, R Grace; Finlin, Brian; Zhu, Beibei; Unal, Resat; Rasouli, Neda; Peterson, Charlotte A; Kern, Philip A

    2016-02-01

    Adipose tissue has profound effects on whole-body insulin sensitivity. However, the underlying biological processes are quite complex and likely multifactorial. For instance, the adipose transcriptome is posttranscriptionally modulated by microRNAs, but the relationship between microRNAs and insulin sensitivity in humans remains to be determined. To this end, we utilized an integrative mRNA-microRNA microarray approach to identify putative molecular interactions that regulate the transcriptome in subcutaneous adipose tissue of insulin-sensitive (IS) and insulin-resistant (IR) individuals. Using the NanoString nCounter Human v1 microRNA Expression Assay, we show that 17 microRNAs are differentially expressed in IR vs. IS. Of these, 16 microRNAs (94%) are downregulated in IR vs. IS, including miR-26b, miR-30b, and miR-145. Using Agilent Human Whole Genome arrays, we identified genes that were predicted targets of miR-26b, miR-30b, and miR-145 and were upregulated in IR subjects. This analysis produced ADAM22, MYO5A, LOX, and GM2A as predicted gene targets of these microRNAs. We then validated that miR-145 and miR-30b regulate these mRNAs in differentiated human adipose stem cells. We suggest that use of bioinformatic integration of mRNA and microRNA arrays yields verifiable mRNA-microRNA pairs that are associated with insulin resistance and can be validated in vitro.

  11. High-Throughput Tissue Bioenergetics Analysis Reveals Identical Metabolic Allometric Scaling for Teleost Hearts and Whole Organisms

    PubMed Central

    Jayasundara, Nishad; Kozal, Jordan S.; Arnold, Mariah C.; Chan, Sherine S. L.; Di Giulio, Richard T.

    2015-01-01

    Organismal metabolic rate, a fundamental metric in biology, demonstrates an allometric scaling relationship with body size. Fractal-like vascular distribution networks of biological systems are proposed to underlie metabolic rate allometric scaling laws from individual organisms to cells, mitochondria, and enzymes. Tissue-specific metabolic scaling is notably absent from this paradigm. In the current study, metabolic scaling relationships of hearts and brains with body size were examined by improving on a high-throughput whole-organ oxygen consumption rate (OCR) analysis method in five biomedically and environmentally relevant teleost model species. Tissue-specific metabolic scaling was compared with organismal routine metabolism (RMO2), which was measured using whole organismal respirometry. Basal heart OCR and organismal RMO2 scaled identically with body mass in a species-specific fashion across all five species tested. However, organismal maximum metabolic rates (MMO2) and pharmacologically-induced maximum cardiac metabolic rates in zebrafish Danio rerio did not show a similar relationship with body mass. Brain metabolic rates did not scale with body size. The identical allometric scaling of heart and organismal metabolic rates with body size suggests that hearts, the power generator of an organism’s vascular distribution network, might be crucial in determining teleost metabolic rate scaling under routine conditions. Furthermore, these findings indicate the possibility of measuring heart OCR utilizing the high-throughput approach presented here as a proxy for organismal metabolic rate—a useful metric in characterizing organismal fitness. In addition to heart and brain OCR, the current approach was also used to measure whole liver OCR, partition cardiac mitochondrial bioenergetic parameters using pharmacological agents, and estimate heart and brain glycolytic rates. This high-throughput whole-organ bioenergetic analysis method has important applications in

  12. High-Throughput Tissue Bioenergetics Analysis Reveals Identical Metabolic Allometric Scaling for Teleost Hearts and Whole Organisms.

    PubMed

    Jayasundara, Nishad; Kozal, Jordan S; Arnold, Mariah C; Chan, Sherine S L; Di Giulio, Richard T

    2015-01-01

    Organismal metabolic rate, a fundamental metric in biology, demonstrates an allometric scaling relationship with body size. Fractal-like vascular distribution networks of biological systems are proposed to underlie metabolic rate allometric scaling laws from individual organisms to cells, mitochondria, and enzymes. Tissue-specific metabolic scaling is notably absent from this paradigm. In the current study, metabolic scaling relationships of hearts and brains with body size were examined by improving on a high-throughput whole-organ oxygen consumption rate (OCR) analysis method in five biomedically and environmentally relevant teleost model species. Tissue-specific metabolic scaling was compared with organismal routine metabolism (RMO2), which was measured using whole organismal respirometry. Basal heart OCR and organismal RMO2 scaled identically with body mass in a species-specific fashion across all five species tested. However, organismal maximum metabolic rates (MMO2) and pharmacologically-induced maximum cardiac metabolic rates in zebrafish Danio rerio did not show a similar relationship with body mass. Brain metabolic rates did not scale with body size. The identical allometric scaling of heart and organismal metabolic rates with body size suggests that hearts, the power generator of an organism's vascular distribution network, might be crucial in determining teleost metabolic rate scaling under routine conditions. Furthermore, these findings indicate the possibility of measuring heart OCR utilizing the high-throughput approach presented here as a proxy for organismal metabolic rate-a useful metric in characterizing organismal fitness. In addition to heart and brain OCR, the current approach was also used to measure whole liver OCR, partition cardiac mitochondrial bioenergetic parameters using pharmacological agents, and estimate heart and brain glycolytic rates. This high-throughput whole-organ bioenergetic analysis method has important applications in

  13. Pyrosequencing of the bacteria associated with Platygyra carnosus corals with skeletal growth anomalies reveals differences in bacterial community composition in apparently healthy and diseased tissues.

    PubMed

    Ng, Jenny C Y; Chan, Yuki; Tun, Hein M; Leung, Frederick C C; Shin, Paul K S; Chiu, Jill M Y

    2015-01-01

    Corals are rapidly declining globally due to coral diseases. Skeletal growth anomalies (SGA) or "coral tumors" are a group of coral diseases that affect coral reefs worldwide, including Hong Kong waters in the Indo-Pacific region. To better understand how bacterial communities may vary in corals with SGA, for the first time, we examined the bacterial composition associated with the apparently healthy and the diseased tissues of SGA-affected Platgyra carnosus using 16S ribosomal rRNA gene pyrosequencing. Taxonomic analysis revealed Proteobacteria, Bacteroidetes, Cyanobacteria, and Actinobacteria as the main phyla in both the apparently healthy and the diseased tissues. A significant difference in the bacterial community composition was observed between the two conditions at the OTU level. Diseased tissues were associated with higher abundances of Acidobacteria and Gemmatimonadetes, and a lower abundance of Spirochaetes. Several OTUs belonging to Rhodobacteraceae, Rhizobiales, Gammaproteobacteria, and Cytophaga-Flavobacterium-Bacteroidetes (CFB) were strongly associated with the diseased tissues. These groups of bacteria may contain potential pathogens involved with the development of SGA or opportunistic secondary or tertiary colonizers that proliferated upon the health-compromised coral host. We suggest that these bacterial groups to be further studied based on inoculation experiments and testing of Koch's postulates in efforts to understand the etiology and progression of SGA.

  14. Pyrosequencing of the bacteria associated with Platygyra carnosus corals with skeletal growth anomalies reveals differences in bacterial community composition in apparently healthy and diseased tissues

    PubMed Central

    Ng, Jenny C. Y.; Chan, Yuki; Tun, Hein M.; Leung, Frederick C. C.; Shin, Paul K. S.; Chiu, Jill M. Y.

    2015-01-01

    Corals are rapidly declining globally due to coral diseases. Skeletal growth anomalies (SGA) or “coral tumors” are a group of coral diseases that affect coral reefs worldwide, including Hong Kong waters in the Indo-Pacific region. To better understand how bacterial communities may vary in corals with SGA, for the first time, we examined the bacterial composition associated with the apparently healthy and the diseased tissues of SGA-affected Platgyra carnosus using 16S ribosomal rRNA gene pyrosequencing. Taxonomic analysis revealed Proteobacteria, Bacteroidetes, Cyanobacteria, and Actinobacteria as the main phyla in both the apparently healthy and the diseased tissues. A significant difference in the bacterial community composition was observed between the two conditions at the OTU level. Diseased tissues were associated with higher abundances of Acidobacteria and Gemmatimonadetes, and a lower abundance of Spirochaetes. Several OTUs belonging to Rhodobacteraceae, Rhizobiales, Gammaproteobacteria, and Cytophaga-Flavobacterium-Bacteroidetes (CFB) were strongly associated with the diseased tissues. These groups of bacteria may contain potential pathogens involved with the development of SGA or opportunistic secondary or tertiary colonizers that proliferated upon the health-compromised coral host. We suggest that these bacterial groups to be further studied based on inoculation experiments and testing of Koch's postulates in efforts to understand the etiology and progression of SGA. PMID:26539174

  15. Rescue of embryonic epithelium reveals that the homozygous deletion of the retinoblastoma gene confers growth factor independence and immortality but does not influence epithelial differentiation or tissue morphogenesis.

    PubMed

    Day, Kathleen C; McCabe, Michael T; Zhao, Xin; Wang, Yuzhuo; Davis, Joanne N; Phillips, John; Von Geldern, Marion; Ried, Thomas; KuKuruga, Mark A; Cunha, Gerald R; Hayward, Simon W; Day, Mark L

    2002-11-15

    The ability to rescue viable prostate precursor tissue from retinoblastoma-deficient (Rb-/-) fetal mice has allowed for the isolation and characterization of the first Rb-/- prostate epithelial cell line. This cell line, designated Rb-/-PrE, was utilized for experiments examining the consequences of Rb loss on an epithelial population. These findings demonstrated that Rb deletion has no discernible effect on prostatic histodifferentiation in Rb-/-PrE cultures. When Rb-/-PrE cells were recombined with embryonic rat urogenital mesenchyme and implanted into athymic male, nude mouse hosts, the recombinants developed into fully differentiated and morphologically normal prostate tissue. The Rb-/-PrE phenotype was characterized by serum independence in culture and immortality in vivo, when compared with wild type controls. Cell cycle analysis revealed elevated S phase DNA content accompanied by increased expression of cyclin E1 and proliferating cell nuclear antigen. Rb-/-PrE cultures also exhibited a diminished ability to growth arrest under high density culture conditions. We believe that the development of Rb-/- prostate tissue and cell lines has provided a unique experimental platform with which to investigate the consequences of Rb deletion in epithelial cells under various physiological conditions. Additionally, the development of this technology will allow similar studies in other tissues and cell populations rescued from Rb-/- fetuses.

  16. Modern reconstructive techniques for abdominal wall defects after oncologic resection.

    PubMed

    Khansa, Ibrahim; Janis, Jeffrey E

    2015-04-01

    Resection of abdominal wall tumors often leaves patients with debilitating soft tissue defects. Modern reconstructive techniques can be used to restore abdominal wall integrity. In this article, we present an overview of preoperative patient evaluation, analysis of the defect, surgical planning, and the spectrum of available surgical techniques, ranging from simple to complex. The established clinical evidence in the field of abdominal wall reconstruction is summarized and a case example is provided.

  17. Proteomic Analysis of Tissue from α1,3-galactosyltransferase Knockout Mice Reveals That a Wide Variety of Proteins and Protein Fragments Change Expression Level

    PubMed Central

    Thorlacius-Ussing, Louise; Ludvigsen, Maja; Kirkeby, Svend

    2013-01-01

    A barrier in a pig-to-man xenotransplantation is that the Galα1-3Galβ1-4GlcNAc-R carbohydrate (α-Gal epitope) expressed on pig endothelial cells reacts with naturally occurring antibodies in the recipient’s blood leading to rejection. Deletion of the α1,3-galactosyltransferase gene prevents the synthesis of the α-Gal epitope. Therefore, knockout models of the α1,3-galactosyltransferase gene are widely used to study xenotransplantation. We have performed proteomic studies on liver and pancreas tissues from wild type and α1,3-galactosyltransferase gene knockout mice. The tissues were analyzed by two-dimensional polyacrylamide gel electrophoresis and liquid chromatography - tandem mass spectrometry. The analyses revealed that a wide variety of proteins and protein fragments are differentially expressed suggesting that knockout of the α1,3-galactosyltransferase gene affects the expression of several other genes. PMID:24244699

  18. Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling

    PubMed Central

    Thomas, Andrew M.; Jesus, Eliane C.; Lopes, Ademar; Aguiar, Samuel; Begnami, Maria D.; Rocha, Rafael M.; Carpinetti, Paola Avelar; Camargo, Anamaria A.; Hoffmann, Christian; Freitas, Helano C.; Silva, Israel T.; Nunes, Diana N.; Setubal, João C.; Dias-Neto, Emmanuel

    2016-01-01

    Sporadic and inflammatory forms of colorectal cancer (CRC) account for more than 80% of cases. Recent publications have shown mechanistic evidence for the involvement of gut bacteria in the development of both CRC-forms. Whereas, colon and rectal cancer have been routinely studied together as CRC, increasing evidence show these to be distinct diseases. Also, the common use of fecal samples to study microbial communities may reflect disease state but possibly not the tumor microenvironment. We performed this study to evaluate differences in bacterial communities found in tissue samples of 18 rectal-cancer subjects when compared to 18 non-cancer controls. Samples were collected during exploratory colonoscopy (non-cancer group) or during surgery for tumor excision (rectal-cancer group). High throughput 16S rRNA amplicon sequencing of the V4–V5 region was conducted on the Ion PGM platform, reads were filtered using Qiime and clustered using UPARSE. We observed significant increases in species richness and diversity in rectal cancer samples, evidenced by the total number of OTUs and the Shannon and Simpson indexes. Enterotyping analysis divided our cohort into two groups, with the majority of rectal cancer samples clustering into one enterotype, characterized by a greater abundance of Bacteroides and Dorea. At the phylum level, rectal-cancer samples had increased abundance of candidate phylum OD1 (also known as Parcubacteria) whilst non-cancer samples had increased abundance of Planctomycetes. At the genera level, rectal-cancer samples had higher abundances of Bacteroides, Phascolarctobacterium, Parabacteroides, Desulfovibrio, and Odoribacter whereas non-cancer samples had higher abundances of Pseudomonas, Escherichia, Acinetobacter, Lactobacillus, and Bacillus. Two Bacteroides fragilis OTUs were more abundant among rectal-cancer patients seen through 16S rRNA amplicon sequencing, whose presence was confirmed by immunohistochemistry and enrichment verified by digital

  19. Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community Profiling.

    PubMed

    Thomas, Andrew M; Jesus, Eliane C; Lopes, Ademar; Aguiar, Samuel; Begnami, Maria D; Rocha, Rafael M; Carpinetti, Paola Avelar; Camargo, Anamaria A; Hoffmann, Christian; Freitas, Helano C; Silva, Israel T; Nunes, Diana N; Setubal, João C; Dias-Neto, Emmanuel

    2016-01-01

    Sporadic and inflammatory forms of colorectal cancer (CRC) account for more than 80% of cases. Recent publications have shown mechanistic evidence for the involvement of gut bacteria in the development of both CRC-forms. Whereas, colon and rectal cancer have been routinely studied together as CRC, increasing evidence show these to be distinct diseases. Also, the common use of fecal samples to study microbial communities may reflect disease state but possibly not the tumor microenvironment. We performed this study to evaluate differences in bacterial communities found in tissue samples of 18 rectal-cancer subjects when compared to 18 non-cancer controls. Samples were collected during exploratory colonoscopy (non-cancer group) or during surgery for tumor excision (rectal-cancer group). High throughput 16S rRNA amplicon sequencing of the V4-V5 region was conducted on the Ion PGM platform, reads were filtered using Qiime and clustered using UPARSE. We observed significant increases in species richness and diversity in rectal cancer samples, evidenced by the total number of OTUs and the Shannon and Simpson indexes. Enterotyping analysis divided our cohort into two groups, with the majority of rectal cancer samples clustering into one enterotype, characterized by a greater abundance of Bacteroides and Dorea. At the phylum level, rectal-cancer samples had increased abundance of candidate phylum OD1 (also known as Parcubacteria) whilst non-cancer samples had increased abundance of Planctomycetes. At the genera level, rectal-cancer samples had higher abundances of Bacteroides, Phascolarctobacterium, Parabacteroides, Desulfovibrio, and Odoribacter whereas non-cancer samples had higher abundances of Pseudomonas, Escherichia, Acinetobacter, Lactobacillus, and Bacillus. Two Bacteroides fragilis OTUs were more abundant among rectal-cancer patients seen through 16S rRNA amplicon sequencing, whose presence was confirmed by immunohistochemistry and enrichment verified by digital

  20. Hepatic resection for breast cancer metastases.

    PubMed Central

    Okaro, A. C.; Durkin, D. J.; Layer, G. T.; Kissin, M. W.; Karanjia, N. D.

    2005-01-01

    INTRODUCTION: Hepatic resection is an established modality of treatment for colorectal cancer metastases. Resection of breast cancer liver metastases remains controversial, but has been shown to be an effective treatment in selected cases. This study reports the outcome of 8 patients with liver metastases from breast cancer. PATIENTS & METHODS: 8 patients with liver metastases from previously treated breast cancer were referred for hepatic resection between September 1996 and December 2002. Six were eligible for liver resection. The mean age was 45.8 years. The resections performed included 1 segmentectomy and 5 hemihepatectomies of which one was an extended hemihepatectomy. One patient had a repeat hepatectomy 44 months after the first resection. RESULTS: There were no postoperative deaths or major morbidity. The resectability rate was 75%. Follow-up periods range from 6 to 70 months with a median survival of 31 months following resection. There have been 2 deaths, one died of recurrence in the residual liver at 6 months and one died disease-free from a stroke. Of the remaining 4 patients, 1 has had a further liver resection at 44 months following which she is alive and 'disease-free' at 70 months. The one patient with peritoneal recurrence is alive 49 months after her liver resection with 2 patients remaining disease-free. CONCLUSION: Hepatic resection for breast cancer liver metastases is a safe procedure with low morbidity and mortality. PMID:15901375

  1. Reconstruction of the extensor mechanism after major knee resection.

    PubMed

    Mavrogenis, Andreas F; Angelini, Andrea; Pala, Elisa; Sakellariou, Vasileios I; Ruggieri, Pietro; Papagelopoulos, Panayiotis J

    2012-05-01

    In periarticular knee resections, the relative lack of soft tissue coverage and need to reattach the extensor mechanism after en bloc resection of the tibial tuberosity with the tumor specimen complicate reconstructions and decrease postoperative function and stability of the knee joint. Distal femoral reconstructions are less problematic; muscular attachments are relatively few, neurovascular structures are not immediately adjacent to bone, and the knee extensor mechanism is usually not compromised from bone tumors. In the proximal tibia, the close proximity of the neurovascular structures in the popliteal fossa and peroneal nerve at the lateral aspect of the leg make reconstruction more difficult. Poor function is mostly related to unreliable options for knee extensor mechanism reattachment and poor soft tissue coverage. Successful and reliable attachment of the soft tissues has been a significant advance that improved functional outcomes.This article describes techniques for the reconstruction of the extensor mechanism of the knee after proximal tibia resections. Combined reconstruction techniques using direct reattachment of the patellar tendon with synthetic materials to megaprosthetic or allograft reconstructions for immediate stability, augmentation with autologous bone graft or substitutes at the attachment site, and coverage with the medial gastrocnemius muscle flap and supplementary flaps for long-term stability of the reattachment are currently considered the gold standard.

  2. Can molecular biomarkers replace a clinical risk score for resectable colorectal liver metastasis?

    PubMed Central

    Veen, Torhild; Søreide, Kjetil

    2017-01-01

    In resectable colorectal liver metastasis (CRLM) the role and use of molecular biomarkers is still controversial. Several biomarkers have been linked to clinical outcomes in CRLM, but none have so far become routine for clinical decision making. For several reasons, the clinical risk score appears to no longer hold the same predictive value. Some of the reasons include the ever expanding indications for liver resection, which now increasingly tend to involve extrahepatic disease, such as lung metastases (both resectable and non-resectable) and the shift in indication from “what is taken out” (e.g., how much liver has to be resected) to “what is left behind” (that is, how much functional liver tissue the patient has after resection). The latter is amenable to modifications by using adjunct techniques of portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy techniques to expand indications for liver resection. Added to this complexity is the increasing number of molecular markers, which appear to hold important prognostic and predictive information, for which some will be discussed here. Beyond characteristics of tissue-based genomic profiles will be liquid biopsies derived from circulating tumor cells and cell-free circulating tumor DNA in the blood. These markers are present in the peripheral circulation in the majority of patients with metastatic cancer disease. Circulating biomarkers may represent more readily available methods to monitor, characterize and predict cancer biology with future implications for cancer care. PMID:28344745

  3. Long-term experience with (laterally) extended endopelvic resection (LEER) in relapsed pelvic malignancies.

    PubMed

    Höckel, Michael

    2015-03-01

    Gynecologic cancers recurring in the pelvis are generally advanced in malignant progression limiting curative treatment approaches. The cancer field theory links cancer progression to reversed morphogenesis and allows the exact anatomical delineation of the cancer field, i.e., the tissue compartment of potential tumor infiltration related to the tumor's ontogenetic stage. Cancer surgery is redefined with the resection of ontogenetic stage-related cancer fields instead of the mere removal of the malignant tumor with an uninvolved tissue margin. Most gynecologic pelvic malignancies recurring in the pelvis represent ontogenetic stages 3 and 4. (Laterally) extended endopelvic resection ((L)EER) has been designed to resect the cancer fields of gynecologic tumors in these advanced ontogenetic stages. This paper reports long-term experience with (L)EER for relapsed pelvic malignancies strongly supporting the cancer field theory and the principle and practice of cancer field resection.

  4. Transcriptomic profiling of citrus fruit peel tissues reveals fundamental effects of phenylpropanoids and ethylene on induced resistance.

    PubMed

    Ballester, Ana-Rosa; Lafuente, M Teresa; Forment, Javier; Gadea, José; De Vos, Ric C H; Bovy, Arnaud G; González-Candelas, Luis

    2011-12-01

    Penicillium spp. are the major postharvest pathogens of citrus fruit in Mediterranean climatic regions. The induction of natural resistance constitutes one of the most promising alternatives to avoid the environmental contamination and health problems caused by chemical fungicides. To understand the bases of the induction of resistance in citrus fruit against Penicillium digitatum, we have used a 12k citrus cDNA microarray to study transcriptional changes in the outer and inner parts of the peel (flavedo and albedo, respectively) of elicited fruits. The elicitor treatment led to an over-representation of biological processes associated with secondary metabolism, mainly phenylpropanoids and cellular amino acid biosynthesis and methionine metabolism, and the down-regulation of genes related to biotic and abiotic stresses. Among phenylpropanoids, we detected the over-expression of a large subset of genes important for the synthesis of flavonoids, coumarins and lignin, especially in the internal tissue. Furthermore, these genes and those of ethylene biosynthesis showed the highest induction. The involvement of both phenylpropanoid and ethylene pathways was confirmed by examining changes in gene expression and ethylene production in elicited citrus fruit. Therefore, global results indicate that secondary metabolism, mainly phenylpropanoids, and ethylene play important roles in the induction of resistance in citrus fruit.

  5. High throughput lipidomic profiling of schizophrenia and bipolar disorder brain tissue reveals alterations of free fatty acids, phosphatidylcholines, and ceramides.

    PubMed

    Schwarz, Emanuel; Prabakaran, Sudhakaran; Whitfield, Phil; Major, Hilary; Leweke, F M; Koethe, Dagmar; McKenna, Peter; Bahn, Sabine

    2008-10-01

    A mass spectrometry based high throughput approach was employed to profile white and gray matter lipid levels in the prefrontal cortex (Brodmann area 9) of 45 subjects including 15 schizophrenia and 15 bipolar disorder patients as well as 15 controls samples. We found statistically significant alterations in levels of free fatty acids and phosphatidylcholine in gray and white matter of both schizophrenia and bipolar disorder samples compared to controls. Also, ceramides were identified to be significantly increased in white matter of both neuropsychiatric disorders as compared to control levels. The patient cohort investigated in this study includes a number of drug naive as well as untreated patients, allowing the assessment of drug effects on lipid levels. Our findings indicate that while gray matter phosphatidylcholine levels were influenced by antipsychotic medication, this was not the case for phosphatidylcholine levels in white matter. Changes in free fatty acids or ceramides in either white or gray matter also did not appear to be influenced by antipsychotic treatment. To assess lipid profiles in the living patient, we also profiled lipids of 40 red blood cell samples, including 7 samples from drug naive first onset patients. We found significant alterations in the concentrations of free fatty acids as well as ceramide. Overall, our findings suggest that lipid abnormalities may be a disease intrinsic feature of both schizophrenia and bipolar disorder reflected by significant changes in the central nervous system as well as peripheral tissues.

  6. Distinct malaria parasite sporozoites reveal transcriptional changes that cause differential tissue infection competence in the mosquito vector and mammalian host.

    PubMed

    Mikolajczak, Sebastian A; Silva-Rivera, Hilda; Peng, Xinxia; Tarun, Alice S; Camargo, Nelly; Jacobs-Lorena, Vanessa; Daly, Thomas M; Bergman, Lawrence W; de la Vega, Patricia; Williams, Jack; Aly, Ahmed S I; Kappe, Stefan H I

    2008-10-01

    The malaria parasite sporozoite transmission stage develops and differentiates within parasite oocysts on the Anopheles mosquito midgut. Successful inoculation of the parasite into a mammalian host is critically dependent on the sporozoite's ability to first infect the mosquito salivary glands. Remarkable changes in tissue infection competence are observed as the sporozoites transit from the midgut oocysts to the salivary glands. Our microarray analysis shows that compared to oocyst sporozoites, salivary gland sporozoites upregulate expression of at least 124 unique genes. Conversely, oocyst sporozoites show upregulation of at least 47 genes (upregulated in oocyst sporozoites [UOS genes]) before they infect the salivary glands. Targeted gene deletion of UOS3, encoding a putative transmembrane protein with a thrombospondin repeat that localizes to the sporozoite secretory organelles, rendered oocyst sporozoites unable to infect the mosquito salivary glands but maintained the parasites' liver infection competence. This phenotype demonstrates the significance of differential UOS expression. Thus, the UIS-UOS gene classification provides a framework to elucidate the infectivity and transmission success of Plasmodium sporozoites on a whole-genome scale. Genes identified herein might represent targets for vector-based transmission blocking strategies (UOS genes), as well as strategies that prevent mammalian host infection (UIS genes).

  7. Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues

    PubMed Central

    Scheller, Erica L.; Doucette, Casey R.; Learman, Brian S.; Cawthorn, William P.; Khandaker, Shaima; Schell, Benjamin; Wu, Brent; Ding, Shi-Ying; Bredella, Miriam A.; Fazeli, Pouneh K.; Khoury, Basma; Jepsen, Karl J.; Pilch, Paul F.; Klibanski, Anne; Rosen, Clifford J.; MacDougald, Ormond A.

    2015-01-01

    Marrow adipose tissue (MAT) accumulates in diverse clinical conditions but remains poorly understood. Here we show region-specific variation in MAT adipocyte development, regulation, size, lipid composition, gene expression and genetic determinants. Early MAT formation in mice is conserved, whereas later development is strain dependent. Proximal, but not distal tibial, MAT is lost with 21-day cold exposure. Rat MAT adipocytes from distal sites have an increased proportion of monounsaturated fatty acids and expression of Scd1/Scd2, Cebpa and Cebpb. Humans also have increased distal marrow fat unsaturation. We define proximal ‘regulated' MAT (rMAT) as single adipocytes interspersed with active haematopoiesis, whereas distal ‘constitutive' MAT (cMAT) has low haematopoiesis, contains larger adipocytes, develops earlier and remains preserved upon systemic challenges. Loss of rMAT occurs in mice with congenital generalized lipodystrophy type 4, whereas both rMAT and cMAT are preserved in mice with congenital generalized lipodystrophy type 3. Consideration of these MAT subpopulations may be important for future studies linking MAT to bone biology, haematopoiesis and whole-body metabolism. PMID:26245716

  8. Resection and debridement of chest-wall tumors and general aspects of reconstruction

    SciTech Connect

    el-Tamer, M.; Chaglassian, T.; Martini, N. )

    1989-10-01

    The main criterion for adequate local control of a chest-wall malignancy remains wide excision. With the available techniques of skeletal and soft-tissue reconstruction, even large lesions can be resected with safe margins. The primary purpose is to achieve a curative resection, although a significant number of symptomatic patients can benefit from palliative resection provided by such procedures. A key element in the success in treating chest-wall tumors is a multidisciplinary approach by all participating physicians, namely the thoracic surgeon, the plastic and reconstructive surgeon, the radiotherapist, and the medical oncologist. 70 references.

  9. Thick lung wedge resection for acute life-threatening massive hemoptysis due to aortobronchial fistula

    PubMed Central

    Ozawa, Yuichiro; Nakajima, Tomomi; Ikeda, Akihiko; Konishi, Taisuke; Matsuzaki, Kanji

    2016-01-01

    Massive hemoptysis from an aortobronchial fistula due to thoracic aortic dissection is an extremely rare symptom, but is a potentially life-threatening condition. We report a case of acute massive hemoptysis due to aortobronchial fistula that was successfully controlled by a simple and rapid thick wedge resection of the lung with hematoma by using the black cartilage stapler. A 65-year-old man was admitted to our hospital with acute massive hemoptysis. After tracheal intubation, chest computed tomography revealed hematoma in the left lung and ruptured aortic dissection from the distal arch to the descending aorta. He was diagnosed with aortobronchial fistula and underwent an emergency surgery on the same day. We performed posterolateral thoracotomy. A dissecting aortic aneurysm (diameter, ~80 mm) with adhesion of the left upper lobe and the superior segment of the lower lobe was found. The lung parenchyma expanded with the hematoma. We stapled the upper and lower lobes by using the black cartridge stapler along the aortopulmonary window. Massive hemoptysis disappeared, and the complete aortic dissection appeared. Aortic dissection with adherent lung was excised, and graft replacement of the distal arch and descending thoracic aorta was performed. Proximal lung wedge resection using black cartridge stapler is a simple and quick method to control massive hemoptysis from aortic dissection; hence, this procedure is an effective option to control massive hemoptysis due to aortobronchial fistula. This technique could rapidly stop massive hemoptysis and prevent dissection of the adherent lung tissue and intra-thoracic bleeding. PMID:27747035

  10. Curative resection for lung cancer in octogenarians is justified

    PubMed Central

    Tutic-Horn, Michaela; Gambazzi, Franco; Rocco, Gaetano; Mosimann, Monique; Schneiter, Didier; Opitz, Isabelle; Martucci, Nono; Hillinger, Sven; Weder, Walter

    2017-01-01

    Background Due to an increased life expectancy in a healthy aging population and a progressive incidence of lung cancer, curative pulmonary resections can be performed even in octogenarians. The present study aims to investigate whether surgery is justified in patients reaching the age of 80 years and older who undergo resection for non-small cell lung cancer (NSCLC). Methods In this retrospective multi-centre analysis, the morbidity, mortality and long-term survival of 88 patients (24 females) aged ≥80 who underwent complete resection for lung cancer between 2000 and 2013 were analysed. Only fit patients with few comorbidities, low cardiopulmonary risk, good quality of life and a life expectancy of at least 5 years were included. Results Curative resections from three thoracic surgery centres included 61 lobectomies, 9 bilobectomies, 6 pneumonectomies and 12 segmentectomies or wide wedge resections with additional systematic mediastinal lymphadenectomy in all cases. Final histology revealed squamous cell carcinoma [33], adenocarcinoma [41], large cell carcinoma [5] or other histological types [9]. Lung cancer stage distribution was 0 [1], I [53], II [17] and IIIA [14]. The overall 90-day mortality was 1.1%. The median hospitalisation and chest drainage times were 10 days (range, 5–27 days) and 5 days (range, 0–17 days), respectively. Thirty-six patients were complication-free (41%). In particular, pulmonary complications occurred in 25 patients (28%). In addition, 23 patients (26%) developed cardiovascular complications requiring medical intervention, while 24 patients (27%) had cerebrovascular complications, urinary tract infection and others. The median survival time was 51 months (range, 1–110 months), and the 5-year overall survival reached 45% without significance between tumour stages. Conclusions Curative lung resections in selected octogenarians can be safely performed up to pneumonectomy for all tumour stages with a perioperative mortality

  11. Strategies for early detection of resectable pancreatic cancer.

    PubMed

    Okano, Keiichi; Suzuki, Yasuyuki

    2014-08-28

    Pancreatic cancer is difficult to diagnose at an early stage and generally has a poor prognosis. Surgical resection is the only potentially curative treatment for pancreatic carcinoma. To improve the prognosis of this disease, it is essential to detect tumors at early stages, when they are resectable. The optimal approach to screening for early pancreatic neoplasia has not been established. The International Cancer of the Pancreas Screening Consortium has recently finalized several recommendations regarding the management of patients who are at an increased risk of familial pancreatic cancer. In addition, there have been notable advances in research on serum markers, tissue markers, gene signatures, and genomic targets of pancreatic cancer. To date, however, no biomarkers have been established in the clinical setting. Advancements in imaging modalities touch all aspects of the clinical management of pancreatic diseases, including the early detection of pancreatic masses, their characterization, and evaluations of tumor resectability. This article reviews strategies for screening high-risk groups, biomarkers, and current advances in imaging modalities for the early detection of resectable pancreatic cancer.

  12. Handling and Pathology Reporting of Gastrointestinal Endoscopic Mucosal Resection

    PubMed Central

    Geramizadeh, Bita; Owen, David A.

    2017-01-01

    Endoscopic mucosal resection (EMR) is a non-invasive alternative to surgery that is now frequently used for resection of early lesions in both upper and lower parts of the gastrointestinal (GI) tract. One of the main advantages of these techniques is providing tissue for histopathological examination. Pathological examination of endoscopically resected specimens of GI tract is a crucial component of these procedures and is useful for prediction of both the risk of metastasis and lymph node involvement. As the first step, it is very important for the pathologist to handle the EMR gross specimen in the correct way: it should be oriented, and then the margins should be labeled and inked accurately before fixation. In the second step, the EMR pathological report should include all the detailed information about the diagnosis, grading, depth of invasion (mucosa only or submucosal involvement), status of the margins, and the presence or absence of lymphovascular invasion. The current literature (PubMed and Google Scholar) was searched for the words "endoscopic mucosal resection" to find all relevant publications about this technique with emphasis on the pathologist responsibilities. PMID:28316760

  13. Sequencing-based approaches reveal low ambient temperature-responsive and tissue-specific microRNAs in phalaenopsis orchid.

    PubMed

    An, Feng-Ming; Hsiao, Shuan-Rung; Chan, Ming-Tsair

    2011-05-06

    Plant small RNAs (smRNAs) are short, non-coding RNA molecules that mediate RNA silencing and regulate a group of genes involved in plant development and responses to environmental stimuli. Low temperature is necessary to initiate stalk development in the orchid Phalaenopsis aphrodite subsp. formosana. To identify smRNAs in Phalaenopsis responding to low temperatures, a smRNA profiling analysis using high-throughput sequencing technology was performed. Subsequent bioinformatic analysis was applied to categorize the miRNAs identified. A total of 37,533,509 smRNA reads yielded 11,129 independent orchid miRNA sequences, representing 329 known miRNA families identified in other plant species. Because the genomic resources available for Phalaenopsis are limited, a transcriptomic database was established using deep sequencing data sets to identify miRNAs precursors and their target transcripts. Comparing small RNAs and the transcriptomic database, 14 putative miRNA precursors of 10 miRNA families were identified, as were hundreds of putative targets. Comparing sequencing data and smRNA northern hybridization results identified miR156, miR162, miR528 and miR535 as low temperature-induced miRNAs. In addition, tissue-specific expression of these miRNAs was investigated. It was concluded that miR156 and miR172 may be components of a regulatory pathway mediating transition from the vegetative to the reproductive phase in Phalaenopsis. The smRNA and transcriptomic databases could be the foundations for further research aimed at elucidating the control of the flowering time in orchids.

  14. Transcriptional Networks in Single Perivascular Cells Sorted from Human Adipose Tissue Reveal a Hierarchy of Mesenchymal Stem Cells.

    PubMed

    Hardy, W Reef; Moldovan, Nicanor I; Moldovan, Leni; Livak, Kenneth J; Datta, Krishna; Goswami, Chirayu; Corselli, Mirko; Traktuev, Dmitry O; Murray, Iain R; Péault, Bruno; March, Keith

    2017-02-24

    Adipose tissue is a rich source of multipotent mesenchymal stem-like cells, located in the perivascular niche. Based on their surface markers, these have been assigned to two main categories: CD31(-) /CD45(-) /CD34(+) /CD146(-) cells (adventitial stromal/stem cells [ASCs]) and CD31(-) /CD45(-) /CD34(-) /CD146(+) cells (pericytes [PCs]). These populations display heterogeneity of unknown significance. We hypothesized that aldehyde dehydrogenase (ALDH) activity, a functional marker of primitivity, could help to better define ASC and PC subclasses. To this end, the stromal vascular fraction from a human lipoaspirate was simultaneously stained with fluorescent antibodies to CD31, CD45, CD34, and CD146 antigens and the ALDH substrate Aldefluor, then sorted by fluorescence-activated cell sorting. Individual ASCs (n = 67) and PCs (n = 73) selected from the extremities of the ALDH-staining spectrum were transcriptionally profiled by Fluidigm single-cell quantitative polymerase chain reaction for a predefined set (n = 429) of marker genes. To these single-cell data, we applied differential expression and principal component and clustering analysis, as well as an original gene coexpression network reconstruction algorithm. Despite the stochasticity at the single-cell level, covariation of gene expression analysis yielded multiple network connectivity parameters suggesting that these perivascular progenitor cell subclasses possess the following order of maturity: (a) ALDH(br) ASC (most primitive); (b) ALDH(dim) ASC; (c) ALDH(br) PC; (d) ALDH(dim) PC (least primitive). This order was independently supported by specific combinations of class-specific expressed genes and further confirmed by the analysis of associated signaling pathways. In conclusion, single-cell transcriptional analysis of four populations isolated from fat by surface markers and enzyme activity suggests a developmental hierarchy among perivascular mesenchymal stem cells supported by markers and

  15. Secretion of Protective Antigens by Tissue-Stage Nematode Larvae Revealed by Proteomic Analysis and Vaccination-Induced Sterile Immunity

    PubMed Central

    Hewitson, James P.; Ivens, Al C.; Harcus, Yvonne; Filbey, Kara J.; McSorley, Henry J.; Murray, Janice; Bridgett, Stephen; Ashford, David; Dowle, Adam A.; Maizels, Rick M.

    2013-01-01

    Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while effectively down-modulating host immune responsiveness. Larvae of Heligmosomoides polygyrus, for example, encyst in the intestinal submucosa, before emerging as adult worms into the duodenal lumen. Adults release immunomodulatory excretory-secretory (ES) products, but mice immunised with adult H. polygyrus ES become fully immune to challenge infection. ES products of the intestinal wall 4th stage (L4) larvae are similarly important in host-parasite interactions, as they readily generate sterile immunity against infection, while released material from the egg stage is ineffective. Proteomic analyses of L4 ES identifies protective antigen targets as well as potential tissue-phase immunomodulatory molecules, using as comparators the adult ES proteome and a profile of H. polygyrus egg-released material. While 135 proteins are shared between L4 and adult ES, 72 are L4 ES-specific; L4-specific proteins correspond to those whose transcription is restricted to larval stages, while shared proteins are generally transcribed by all life cycle forms. Two protein families are more heavily represented in the L4 secretome, the Sushi domain, associated with complement regulation, and the ShK/SXC domain related to a toxin interfering with T cell signalling. Both adult and L4 ES contain extensive but distinct arrays of Venom allergen/Ancylostoma secreted protein-Like (VAL) members, with acetylcholinesterases (ACEs) and apyrase APY-3 particularly abundant in L4 ES. Serum antibodies from mice vaccinated with L4 and adult ES react strongly to the VAL-1 protein and to ACE-1, indicating that these two antigens represent major vaccine targets for this intestinal nematode. We have thus defined an extensive and novel repertoire of H

  16. Knockdown expression and hepatic deficiency reveal anatheroprotective role for SR-BI in liver and peripheral tissues

    SciTech Connect

    Huby, Thierry; Doucet, Chantal; Dachet, Christiane; Ouzilleau,Betty; Ueda, Yukihiko; Afzal, Veena; Rubin, Edward; Chapman, M. John; Lesnik, Philippe

    2006-07-18

    Scavenger receptor SR-BI has been implicated inHDL-dependent atheroprotective mechanisms. We report the generation of anSR-BI conditional knockout mouse model in which SR-BI gene targeting byloxP site insertion produced a hypomorphic allele (hypomSR-BI).Attenuated SR-BI expression in hypomSR-BI mice resulted in 2-foldelevation in plasma total cholesterol (TC) levels. Cre-mediated SR-BIgene inactivation of the hypomorphic SR-BI allele in hepatocytes(hypomSR-BI-KOliver) was associated with high plasma TC concentrations,increased plasma free cholesterol/TC (FC/TC) ratio, and alipoprotein-cholesterol profile typical of SR-BI-/- mice. Plasma TClevels were increased 2-fold in hypomSR-BI and control mice fed anatherogenic diet, whereas hypomSR-BI-KOliver and SR-BI-/- mice developedsevere hypercholesterolemia due to accumulation of FC-rich, VLDL-sizedparticles. Atherosclerosis in hypomSR-BI mice was enhanced (2.5-fold)compared with that in controls, but to a much lower degree than inhypomSR-BI-KOliver (32-fold) and SR-BI-/- (48-fold) mice. The lattermodels did not differ in either plasma lipid levels or in the capacity ofVLDL-sized lipoproteins to induce macrophage cholesterol loading.However, reduced atherosclerosis in hypomSR-BI-KOliver mice wasassociated with decreased lesional macrophage content as compared withthat in SR-BI-/- mice. These data imply that, in addition to its majoratheroprotective role in liver, SR-BI may exert an antiatherogenic rolein extrahepatic tissues.

  17. Tissue-specific signaling networks rewired by major somatic mutations in human cancer revealed by proteome-wide discovery.

    PubMed

    Zhao, Junfei; Cheng, Feixiong; Zhao, Zhongming

    2017-03-31

    Massive somatic mutations discovered by large cancer genome sequencing projects provide unprecedented opportunities in the development of precision oncology. However, deep understanding of functional consequences of somatic mutations and identifying actionable mutations and the related drug responses currently remain formidable challenges. Dysfunction of protein post-translational modification plays critical roles in tumorigenesis and drug responses. In this study, we proposed a novel computational oncoproteomics approach, named kinome-wide network module for cancer pharmacogenomics (KNMPx), for identifying actionable mutations that rewired signaling networks and further characterized tumorigenesis and anticancer drug responses. Specifically, we integrated 746,631 missense mutations in 4,997 tumor samples across 16 major cancer types/subtypes from The Cancer Genome Atlas into over 170,000 carefully curated non-redundant phosphorylation sites covering 18,610 proteins. We found 47 mutated proteins (e.g., ERBB2, TP53, and CTNNB1) that had enriched missense mutations at their phosphorylation sites in pan-cancer analysis. In addition, tissue-specific kinase-substrate interaction modules altered by somatic mutations identified by KNMPx were significantly associated with patient survival. We further reported a kinome-wide landscape of pharmacogenomic interactions by incorporating somatic mutation-rewired signaling networks in 1,001 cancer cell lines via KNMPx. Interestingly, we found that cell lines could highly reproduce oncogenic phosphorylation site mutations identified in primary tumors, supporting the confidence in their associations with sensitivity/resistance of inhibitors targeting EGF, MAPK, PI3K, mTOR, and Wnt signaling pathways. In summary, this systematic oncoproteomics analysis of kinome phosphorylation site mutations illustrates new capabilities to speed the development of precision oncology.

  18. Ultra-deep sequencing detects ovarian cancer cells in peritoneal fluid and reveals somatic TP53 mutations in noncancerous tissues.

    PubMed

    Krimmel, Jeffrey D; Schmitt, Michael W; Harrell, Maria I; Agnew, Kathy J; Kennedy, Scott R; Emond, Mary J; Loeb, Lawrence A; Swisher, Elizabeth M; Risques, Rosa Ana

    2016-05-24

    Current sequencing methods are error-prone, which precludes the identification of low frequency mutations for early cancer detection. Duplex sequencing is a sequencing technology that decreases errors by scoring mutations present only in both strands of DNA. Our aim was to determine whether duplex sequencing could detect extremely rare cancer cells present in peritoneal fluid from women with high-grade serous ovarian carcinomas (HGSOCs). These aggressive cancers are typically diagnosed at a late stage and are characterized by TP53 mutations and peritoneal dissemination. We used duplex sequencing to analyze TP53 mutations in 17 peritoneal fluid samples from women with HGSOC and 20 from women without cancer. The tumor TP53 mutation was detected in 94% (16/17) of peritoneal fluid samples from women with HGSOC (frequency as low as 1 mutant per 24,736 normal genomes). Additionally, we detected extremely low frequency TP53 mutations (median mutant fraction 1/13,139) in peritoneal fluid from nearly all patients with and without cancer (35/37). These mutations were mostly deleterious, clustered in hotspots, increased with age, and were more abundant in women with cancer than in controls. The total burden of TP53 mutations in peritoneal fluid distinguished cancers from controls with 82% sensitivity (14/17) and 90% specificity (18/20). Age-associated, low frequency TP53 mutations were also found in 100% of peripheral blood samples from 15 women with and without ovarian cancer (none with hematologic disorder). Our results demonstrate the ability of duplex sequencing to detect rare cancer cells and provide evidence of widespread, low frequency, age-associated somatic TP53 mutation in noncancerous tissue.

  19. Ligation-assisted endoscopic submucosal resection with circumferential mucosal incision for duodenal carcinoid tumor.

    PubMed

    Harada, Hideaki; Suehiro, Satoshi; Shimizu, Takanori; Katsuyama, Yasushi; Hayasaka, Kenji; Ito, Hideto

    2015-09-14

    Here we present the case of a 64-year-old female with a duodenal carcinoid tumor treated by ligation-assisted endoscopic submucosal resection (ESMR-L) with circumferential mucosal incision (CMI). Band ligation was effective in resecting the duodenal carcinoid tumor after CMI, with an uneventful post-procedural course. Histopathological examination showed clear tumor margins at deeper tissue levels. Thus, in the present case, ESMR-L with CMI was useful for the treatment of duodenal carcinoid tumor.

  20. Isolated port-site metastasis of hepatocellular carcinoma after laparoscopic liver resection.

    PubMed

    Kihara, Kyoichi; Endo, Kanenori; Suzuki, Kazunori; Nakamura, Seiichi; Sawata, Takashi; Shimizu, Tetsu; Ikeguchi, Masahide; Tokuyasu, Yusuke; Nakamoto, Shu

    2016-10-17

    Port-site metastasis of hepatocellular carcinoma (HCC) is extremely rare, and only one case has been reported in the English-language literature. Contamination with malignant cells along the needle tract during percutaneous biopsy or radiofrequency ablation is a well-recognized cause of HCC recurrence. Here, we describe a case of port-site metastasis after laparoscopic liver resection of HCC. The patient, who had undergone laparoscopic partial resection of the left lateral segment of the liver 18 months earlier, was diagnosed with HCC. CT showed a nodule in the abdominal wall where the laparoscopic port had been inserted during resection. Local excision was performed, and histological examination revealed HCC consistent with recurrence after laparoscopic resection. The experience described in this report highlights the risk of port-site metastasis of HCC. Imaging for oncologic surveillance after laparoscopic resection must include all port sites.

  1. Podoplanin expression in tumor-free resection margins of oral squamous cell carcinomas: an immunohistochemical and fractal analysis study.

    PubMed

    Margaritescu, C; Raica, M; Pirici, D; Simionescu, C; Mogoanta, L; Stinga, A C; Stinga, A S; Ribatti, D

    2010-06-01

    Podoplanin is involved in tumorigenesis and cancer progression in head and neck malignancies and its expression is not restricted to lymphatic vessel endothelium. The aim of this study was to establish podoplanin expression in the tumor-free resection margins of oral squamous cell carcinomas (OSCCs) and to evaluate the geometric complexity of the lymphatic vessels in oral mucosa by utilizing fractal analysis. As concerns the podoplanin expression in noncancerous tissue, forty tumor-free resection margins from OSCCs were investigated utilizing immunohistochemistry for D2-40 antibody and image densitometry analysis. Podoplanin expression was extremely low in basal cells, especially in resection margins of OSCCs developed in the lower lip regions. However, a highly variable D2-40 expression in tumor-free resection margins associated with hyperplastic or dysplastic lesions was identified. Moreover, podoplanin expression also extended to the basal layer of the lower lip skin appendages, the myoepithelial cells of acini and ducts of minor salivary glands, and other structures from the oral cavity. As concerns the study of the density and complexity of oral lymphatic vessels architecture by means of immunohistochemistry (D2-40, CD31 and Ki-67 antibodies) and fractal analysis, we demonstrated that in normal oral mucosa the geometry of the lymphatic vessels was less complex at the level of the lower lip compared to the anterior part of the oral floor mucosa or the tongue. A comparative analysis between the normal and pathological aspects revealed statistically significant differences between the fractal dimension (FD) of the vessels' outline, especially in the tongue. Fractal analysis proved an increasing lymphatic network complexity from normal to premalignant oral mucosal lesions, providing additional prognostic information in oral malignant tumors.

  2. Comparative Genomic, MicroRNA, and Tissue Analyses Reveal Subtle Differences between Non-Diabetic and Diabetic Foot Skin.

    PubMed

    Ramirez, Horacio A; Liang, Liang; Pastar, Irena; Rosa, Ashley M; Stojadinovic, Olivera; Zwick, Thomas G; Kirsner, Robert S; Maione, Anna G; Garlick, Jonathan A; Tomic-Canic, Marjana

    2015-01-01

    complications, or duration of DM, may further compromise tissue's healing ability leading to development of DFUs.

  3. Hinge bending within the cytokine receptor superfamily revealed by the 2.4 A crystal structure of the extracellular domain of rabbit tissue factor.

    PubMed Central

    Muller, Y. A.; Kelley, R. F.; de Vos, A. M.

    1998-01-01

    Tissue factor (TF), a member of the cytokine receptor superfamily, is the obligate cofactor of coagulation factor VIIa (FVIIa), and has a pivotal role in initiating the extrinsic pathway of blood coagulation through formation of the TF x FVIIa complex. The crystal structure of the extracellular portion of rabbit TF has been solved at 2.35 A resolution and refined to a crystallographic R-value of 19.1% (free R-value, 27.7%). Like the human homologue, the extracellular portion consists of two fibronectin type III domains connected by a short alpha-helical segment. Unexpectedly, the two molecules in the crystallographic asymmetric unit differ in their relative domain-domain orientation, revealing unsuspected hinge motion consisting of a rotation of about 12.7 degrees around an axis intersecting the linker segment at residue 106. Superposition of rabbit tissue factor with free and bound human tissue factor allows for the detection of an identical, albeit smaller, hinge motion in human TF induced upon binding of FVIIa. This raises the possibility that a very similar hinge axis may be present in other members of the cytokine receptor superfamily. PMID:9605315

  4. New Insights on Human Skeletal Muscle Tissue Compartments Revealed by In Vivo T2 NMR Relaxometry

    PubMed Central

    Araujo, Ericky C.A.; Fromes, Yves; Carlier, Pierre G.

    2014-01-01

    The spin-spin (T2) relaxation of 1H-NMR signals in human skeletal muscle has been previously hypothesized to reveal information about myowater compartmentation. Although experimental support has been provided, no consensus has yet emerged concerning the attribution of specific anatomical compartments to the observed T2 components. Potential application of a noninvasive tool that might offer such information urges the quest for a definitive answer to this question. The purpose of this work was to obtain new information that might help elucidate the mechanism of T2 distribution in muscle. To do so, in vivo T2 relaxation data was acquired from the soleus of eight healthy volunteers using a localized Carr-Purcell-Meiboom-Gill technique. Each acquisition contained 1000 echoes with an interecho spacing of 1 ms. Data were acquired from each subject under different vascular filling preparations expected to change exclusively the extracellular water fraction. Two exponential components were systematically observed: an intermediate component (T2 ∼ 32 ms) and a long component (100 < T2 < 210 ms). The relative fraction and T2 value characterizing the long component systematically increased after progressive augmentation of extracellular water volume. Characteristic relaxation behavior for each vascular filling condition was analyzed with a two-site exchange model and a three-site two-exchange model. We show that a two-site exchange model can only predict the observations for small exchange rates, much more representative of transendothelial than transcytolemmal exchange regimes. The three-site two-exchange model representing the intracellular, interstitial, and vascular spaces was capable of precisely predicting the observations for realistic transcytolemmal and transendothelial exchange rates. The estimated intrinsic relative fractions of each of these compartments corroborate with estimations from previous works and strongly suggest that the T2 relaxation from

  5. Revealing the Molecular Portrait of Triple Negative Breast Tumors in an Understudied Population through Omics Analysis of Formalin-Fixed and Paraffin-Embedded Tissues

    PubMed Central

    Vaca-Paniagua, Felipe; Alvarez-Gomez, Rosa María; Maldonado-Martínez, Hector Aquiles; Pérez-Plasencia, Carlos; Fragoso-Ontiveros, Veronica; Lasa-Gonsebatt, Federico; Herrera, Luis Alonso; Cantú, David; Bargallo-Rocha, Enrique; Mohar, Alejandro; Durand, Geoffroy; Forey, Nathalie; Voegele, Catherine; Vallée, Maxime; Le Calvez-Kelm, Florence; McKay, James; Ardin, Maude; Villar, Stéphanie; Zavadil, Jiri; Olivier, Magali

    2015-01-01

    Triple negative breast cancer (TNBC), defined by the lack of expression of the estrogen receptor, progesterone receptor and human epidermal receptor 2, is an aggressive form of breast cancer that is more prevalent in certain populations, in particular in low- and middle-income regions. The detailed molecular features of TNBC in these regions remain unexplored as samples are mostly accessible as formalin-fixed paraffin embedded (FFPE) archived tissues, a challenging material for advanced genomic and transcriptomic studies. Using dedicated reagents and analysis pipelines, we performed whole exome sequencing and miRNA and mRNA profiling of 12 FFPE tumor tissues collected from pathological archives in Mexico. Sequencing analyses of the tumor tissues and their blood pairs identified TP53 and RB1 genes as the most frequently mutated genes, with a somatic mutation load of 1.7 mutations/exome Mb on average. Transcriptional analyses revealed an overexpression of growth-promoting signals (EGFR, PDGFR, VEGF, PIK3CA, FOXM1), a repression of cell cycle control pathways (TP53, RB1), a deregulation of DNA-repair pathways, and alterations in epigenetic modifiers through miRNA:mRNA network de-regulation. The molecular programs identified were typical of those described in basal-like tumors in other populations. This work demonstrates the feasibility of using archived clinical samples for advanced integrated genomics analyses. It thus opens up opportunities for investigating molecular features of tumors from regions where only FFPE tissues are available, allowing retrospective studies on the search for treatment strategies or on the exploration of the geographic diversity of breast cancer. PMID:25961742

  6. Revealing the Molecular Portrait of Triple Negative Breast Tumors in an Understudied Population through Omics Analysis of Formalin-Fixed and Paraffin-Embedded Tissues.

    PubMed

    Vaca-Paniagua, Felipe; Alvarez-Gomez, Rosa María; Maldonado-Martínez, Hector Aquiles; Pérez-Plasencia, Carlos; Fragoso-Ontiveros, Veronica; Lasa-Gonsebatt, Federico; Herrera, Luis Alonso; Cantú, David; Bargallo-Rocha, Enrique; Mohar, Alejandro; Durand, Geoffroy; Forey, Nathalie; Voegele, Catherine; Vallée, Maxime; Le Calvez-Kelm, Florence; McKay, James; Ardin, Maude; Villar, Stéphanie; Zavadil, Jiri; Olivier, Magali

    2015-01-01

    Triple negative breast cancer (TNBC), defined by the lack of expression of the estrogen receptor, progesterone receptor and human epidermal receptor 2, is an aggressive form of breast cancer that is more prevalent in certain populations, in particular in low- and middle-income regions. The detailed molecular features of TNBC in these regions remain unexplored as samples are mostly accessible as formalin-fixed paraffin embedded (FFPE) archived tissues, a challenging material for advanced genomic and transcriptomic studies. Using dedicated reagents and analysis pipelines, we performed whole exome sequencing and miRNA and mRNA profiling of 12 FFPE tumor tissues collected from pathological archives in Mexico. Sequencing analyses of the tumor tissues and their blood pairs identified TP53 and RB1 genes as the most frequently mutated genes, with a somatic mutation load of 1.7 mutations/exome Mb on average. Transcriptional analyses revealed an overexpression of growth-promoting signals (EGFR, PDGFR, VEGF, PIK3CA, FOXM1), a repression of cell cycle control pathways (TP53, RB1), a deregulation of DNA-repair pathways, and alterations in epigenetic modifiers through miRNA:mRNA network de-regulation. The molecular programs identified were typical of those described in basal-like tumors in other populations. This work demonstrates the feasibility of using archived clinical samples for advanced integrated genomics analyses. It thus opens up opportunities for investigating molecular features of tumors from regions where only FFPE tissues are available, allowing retrospective studies on the search for treatment strategies or on the exploration of the geographic diversity of breast cancer.

  7. FTIR imaging of brain tissue reveals crystalline creatine deposits are an ex vivo marker of localized ischemia during murine cerebral malaria: general implications for disease neurochemistry.

    PubMed

    Hackett, Mark J; Lee, Joonsup; El-Assaad, Fatima; McQuillan, James A; Carter, Elizabeth A; Grau, Georges E; Hunt, Nicholas H; Lay, Peter A

    2012-12-19

    Phosphocreatine is a major cellular source of high energy phosphates, which is crucial to maintain cell viability under conditions of impaired metabolic states, such as decreased oxygen and energy availability (i.e., ischemia). Many methods exist for the bulk analysis of phosphocreatine and its dephosphorylated product creatine; however, no method exists to image the distribution of creatine or phosphocreatine at the cellular level. In this study, Fourier transform infrared (FTIR) spectroscopic imaging has revealed the ex vivo development of creatine microdeposits in situ in the brain region most affected by the disease, the cerebellum of cerebral malaria (CM) diseased mice; however, such deposits were also observed at significantly lower levels in the brains of control mice and mice with severe malaria. In addition, the number of deposits was observed to increase in a time-dependent manner during dehydration post tissue cutting. This challenges the hypotheses in recent reports of FTIR spectroscopic imaging where creatine microdeposits found in situ within thin sections from epileptic, Alzheimer's (AD), and amlyoid lateral sclerosis (ALS) diseased brains were proposed to be disease specific markers and/or postulated to contribute to the brain pathogenesis. As such, a detailed investigation was undertaken, which has established that the creatine microdeposits exist as the highly soluble HCl salt or zwitterion and are an ex-vivo tissue processing artifact and, hence, have no effect on disease pathogenesis. They occur as a result of creatine crystallization during dehydration (i.e., air-drying) of thin sections of brain tissue. As ischemia and decreased aerobic (oxidative metabolism) are common to many brain disorders, regions of elevated creatine-to-phosphocreatine ratio are likely to promote crystal formation during tissue dehydration (due to the lower water solubility of creatine relative to phosphocreatine). The results of this study have demonstrated that

  8. Laterally extended endopelvic resection (LEER)--principles and practice.

    PubMed

    Höckel, Michael

    2008-11-01

    Exenteration has been used for the last 6 decades, mainly to treat cancers of the lower and middle female genital tract in the irradiated pelvis. New ablative techniques based on developmentally derived surgical anatomy termed laterally extended endopelvic resection (LEER) aim to increase the curative resection rate, even of tumors extending to and fixed to the pelvic side wall. LEER is performed as a combination of at least two of the following procedures: total mesorectal excision, total mesometrial resection, and total mesovesical resection. In cases of lateral tumor fixation, the inclusion of pelvic side wall and floor muscles, such as the obturator internus muscle and pubococcygeus, iliococcygeus and coccygeus muscles, and eventually of the internal iliac vessel system assures the completeness of the multicompartmental resection. One hundred patients with locally advanced (n=25) and recurrent (n=75) gynecologic tumors have been treated with these new procedures. In 76 patients, the tumors were fixed to the pelvic side wall. Two patients with advanced age and extensive comorbidity died during the early postoperative period. Moderate and severe treatment-related morbidity was 70%, mainly due to compromised healing of irradiated tissue and the performance of complex reconstructions. At a median follow-up period of 30 months (range, 1-136 months), 5-year recurrence-free and disease-specific overall survival probabilities are 62% (95% CI, 52-72%) and 55% (95% CI, 43-67%), respectively. LEER has significant potential to salvage selected patients with locally advanced and recurrent gynecologic malignancies, including those with pelvic side wall disease, traditionally not considered for surgical therapy.

  9. Shifting sources of functional limitation following extensive (70%) lung resection.

    PubMed

    Hsia, Connie C W; Dane, D Merrill; Estrera, Aaron S; Wagner, Harrieth E; Wagner, Peter D; Johnson, Robert L

    2008-04-01

    We previously found that, following surgical resection of approximately 58% of lung units by right pneumonectomy (PNX) in adult canines, oxygen-diffusing capacity (Dl(O(2))) fell sufficiently to become a major factor limiting exercise capacity, although the decline was mitigated by recruitment, remodeling, and growth of the remaining lung units. To determine whether an upper limit of compensation is reached following the loss of even more lung units, we measured pulmonary gas exchange, hemodynamics, and ventilatory power requirements in adult canines during treadmill exercise following two-stage resection of approximately 70% of lung units in the presence or absence of mediastinal distortion. Results were compared with that in control animals following right PNX or thoracotomy without resection (Sham). Following 70% lung resection, peak O(2) uptake was 45% below normal. Ventilation-perfusion mismatch developed, and pulmonary arterial pressure and ventilatory power requirements became markedly elevated. In contrast, the relationship of Dl(O(2)) to cardiac output remained normal, indicating preservation of Dl(O(2))-to-cardiac output ratio and alveolar-capillary recruitment up to peak exercise. The impairment in airway and vascular function exceeded the impairment in gas exchange and imposed the major limitation to exercise following 70% resection. Mediastinal distortion further reduced air and blood flow conductance, resulting in CO(2) retention. Results suggest that adaptation of extra-acinar airways and blood vessels lagged behind that of acinar tissue. As more lung units were lost, functional compensation became limited by the disproportionately reduced convective conductance rather than by alveolar diffusion disequilibrium.

  10. Precision resection of intestine using ultrashort laser pulses

    NASA Astrophysics Data System (ADS)

    Beck, Rainer J.; Gora, Wojciech S.; Jayne, David; Hand, Duncan P.; Shephard, Jonathan D.

    2016-03-01

    Endoscopic resection of early colorectal neoplasms typically employs electrocautery tools, which lack precision and run the risk of full thickness thermal injury to the bowel wall with subsequent perforation. We present a means of endoluminal colonic ablation using picosecond laser pulses as a potential alternative to mitigate these limitations. High intensity ultrashort laser pulses enable nonlinear absorption processes, plasma generation, and as a consequence a predominantly non-thermal ablation regimen. Robust process parameters for the laser resection are demonstrated using fresh ex vivo pig intestine samples. Square cavities with comparable thickness to early colorectal neoplasms are removed for a wavelength of 1030 nm and 515 nm using a picosecond laser system. The corresponding histology sections exhibit in both cases only minimal collateral damage to the surrounding tissue. The ablation depth can be controlled precisely by means of the pulse energy. Overall, the application of ultrafast lasers for the resection of intestine enables significantly improved precision and reduced thermal damage to the surrounding tissue compared to conventional electrocautery.

  11. Resection replantation of the upper limb for aggressive malignant tumors.

    PubMed

    El-Gammal, Tarek Abdalla; El-Sayed, Amr; Kotb, Mohamed Mostafa

    2002-04-01

    Stage IIB malignant tumors of the upper limb have been traditionally treated by amputation or disarticulation. There have been isolated reports on the technique of segmental resection of the tumor-bearing segment complete with the skin, and replanting the distal arm or forearm with or without neurovascular repair. The present paper describes four cases in which a wide resection margin was achieved in all by resecting the affected cylinder of the limb. Functional reconstruction was performed by appropriate tendon transfer. The main vessels and nerves were dealt with according to the findings revealed by preoperative investigations. If they had to be sacrificed, end-to-end suture was performed, but if the main nerves could be spared, it greatly enhanced the functional outcome. Local and systemic recurrences occurred in one case, and systemic recurrence occurred in another case. The other two cases remained disease-free at more than 4 years' follow-up. This operation is as radical as amputation, while the esthetic and functional results are equivalent to those of resection-arthrodesis.

  12. Long-term survival of a patient with metachronous rectal metastasis from primary cecal cancer who underwent repetitive resection and chemotherapy: a case report.

    PubMed

    Shimazaki, Jiro; Nakachi, Takeshi; Tabuchi, Takanobu; Ubukata, Hideyuki; Tabuchi, Takafumi

    2014-04-23

    There are few reported cases of colorectal metastasis from cancers of other organs, particularly other segments of the colon. Here we describe the long-term survival of a 68-year-old male patient with metachronous rectal metastasis from cecal cancer who underwent repetitive resection and chemotherapy. The patient underwent ileocecal resection and hepatectomy for cecal cancer with liver metastasis (T3, N1a, M1a, Stage IVA) in 2006. The patient subsequently underwent splenectomy for splenic metastasis in 2007. In August 2008, barium enema revealed compression of the rectal wall, and abdominal computed tomography (CT) detected a mass along the rectum extending into the pelvis. Rectal metastasis from cecal cancer was suspected and Hartmann's operation with bilateral seminal vesicle dissection was performed. Histological examination of the excised tumor revealed moderately differentiated adenocarcinoma formed in the muscularis propria of the rectum and infiltrating the connective tissue between the seminal vesicle and rectum. However, no tumor was detected in the rectal mucosa or submucosa. These histological findings supported the diagnosis of rectal metastasis from cecal cancer. The patient has been monitored at our clinic for 60 months after surgical removal of the rectal metastasis. The findings from this case should alert oncologists to the potential danger of rectal metastasis from primary colon cancer and the benefits of timely complete resection in terms of improved patient outcomes.

  13. Endoscopic transnasal resection of ameloblastoma with intracranial extension.

    PubMed

    Woodroffe, Royce W; Abel, Taylor J; Fletcher, Aaron; Grossbach, Andrew; Van Daele, Douglas J; O'Brien, Erin; Greenlee, Jeremy D W

    2014-05-01

    Ameloblastoma is a rare odontogenic tumor with characteristics of epithelial tissue that produces enamel for the developing tooth. This lesion is generally considered benign, but has malignant forms that invade locally and metastasize. We present a 60-year-old man with maxillary ameloblastoma that after multiple recurrences developed intracranial extension with dural involvement of the middle cranial fossa and was treated by endoscopic transnasal resection followed by radiation therapy. Our technique and intraoperative findings are described with a review of the literature on intracranial ameloblastoma. This patient represents a unique account of endoscopic transnasal resection being utilized in the treatment of intracranial extension of ameloblastoma and demonstrates potential for application in similar cases.

  14. Risk assessment for pulmonary resection.

    PubMed

    Brunelli, Alessandro

    2010-01-01

    Risk assessment for pulmonary resection must include a preliminary cardiac evaluation. Patients deemed at prohibitive cardiac risk should be evaluated and treated as per American Heart Association/American Society of Cardiology guidelines. Those with low cardiac risk or with optimized treatment can proceed with pulmonary assessment. A systematic measurement of lung carbon monoxide diffusing capacity is recommended. In addition, predicted postoperative forced expiratory volume in 1 second should not be used alone for patient selection because it is not an accurate predictor of complications, particularly in patients with chronic obstructive pulmonary disease. The use of exercise testing should be emphasized. Low-technology tests, such as stair climbing, can be used whenever a formal cardiopulmonary exercise test is not readily available. However, in case of suboptimal performance (ie, <22 m in the stair-climbing test) patients should be referred to cardiopulmonary exercise testing with measurement of Vo(2max) for a better definition of their aerobic reserve. A Vo(2max) less than 10 mL/kg/min (or <35% of predicted) indicates a high risk for major lung resection.

  15. An enlarged intramuscular venous malformation in the femoral region successfully treated with complete resection

    PubMed Central

    Murakami, Takuo; Ogata, Dai; Miyano, Kyohei; Tsuchida, Tetsuya

    2016-01-01

    Introduction Intramuscular venous malformations have been previously described as intramuscular hemangiomas, and various therapies have been applied for their treatment. This condition is relatively rare, and therefore, physicians often struggle to determine the appropriate therapy. We presented a case of an enlarged intramuscular venous malformation relapsed after surgery successfully treated with complete resection. Presentation of case We presented a case of an enlarged intramuscular venous malformation with postoperative recurrence successfully treated with complete resection. A 63-year-old woman presented with a subcutaneous mass in the right distal thigh. She experienced swelling in the right thigh 19 years previously and was diagnosed with a venous aneurysm. Three-dimensional CT angiography confirmed the presence of an irregular vessel assumed to be the feeding vessel, which was dendritically branched from the deep femoral artery. We performed surgical complete resection. Her pain and gait disturbance improved after surgery, and she has not experienced recurrence of the mass for the past 2 years. Discussion Conservative therapy is initially used for venous malformations. Sclerotherapy, laser therapy, or surgical resection is considered after low-dose aspirin therapy, in combination with the use of compressive garments. Surgical resection is indicated for completely resectable lesions and is appropriate for large lesions in terms of cosmetic benefit. However, partial resection may result in excessive bleeding or postoperative recurrence. Conclusion The therapy for venous malformations should be decided based on the degree of disability in daily living, adjacent tissue damage, and cosmetic concerns after appropriate differential diagnostic investigations and biopsy. PMID:26945489

  16. The effect of preceding biopsy on complete endoscopic resection in rectal carcinoid tumor.

    PubMed

    Lee, Sang Pyo; Sung, In-Kyung; Kim, Jeong Hwan; Lee, Sun-Young; Park, Hyung Seok; Shim, Chan Sup

    2014-04-01

    Biopsy of rectal carcinoid tumor is commonly taken before endoscopic resection. However the preceding biopsy can inhibit complete resection by causing blurred tumor border and fibrosis of the tissue. The objective of the study was to investigate the effect of preceding biopsy on complete endoscopic resection in rectal carcinoid tumor. It was also determined if rectal carcinoid tumors can be macroscopically distinguished by endoscopy. We reviewed retrospectively the records of patients with rectal carcinoid tumor who had undergone an endoscopic treatment at our hospital, during a 7-yr period. The resection margin was clear in 57 of 98 cases. The preceding biopsy was taken in 57 cases and the biopsy was significantly associated with the risk of incomplete tumor resection (OR, 3.696; 95% CI, 1.528-8.938, P = 0.004). In 95.9% of the cases, it was possible to suspect a carcinoid tumor by macroscopic appearance during initial endoscopy. The preceding biopsy may disturb complete resection of rectal carcinoid tumor. In most cases, the carcinoid tumor could be suspected by macroscopic appearance. Therefore the preceding biopsy is not essential, and it may be avoided for the complete resection.

  17. Awake operative videothoracoscopic pulmonary resections.

    PubMed

    Pompeo, Eugenio; Mineo, Tommaso C

    2008-08-01

    The authors' initial experience with awake videothoracoscopic lung resection suggests that these procedures can be easily and safely performed under sole thoracic epidural anesthesia with no mortality and negligible morbidity. One major concern was that operating on a ventilating lung would render surgical maneuvers more difficult because of the lung movements and lack of a sufficient operating space. Instead, the open pneumothorax created after trocar insertion produces a satisfactory lung collapse that does not hamper surgical maneuvers. These results contradict the accepted assumption that the main prerequisite for allowing successful thoracoscopic lung surgery is general anesthesia with one-lung ventilation. No particular training is necessary to accomplish an awake pulmonary resection for teams experienced in thoracoscopic surgery, and conversions to general anesthesia are mainly caused by the presence of extensive fibrous pleural adhesions or the development of intractable panic attacks. Overall, awake pulmonary resection is easily accepted and well tolerated by patients, as confirmed by the high anesthesia satisfaction score, which was better than in nonawake control patients. Nonetheless, thoracic epidural anesthesia has potential complications, including epidural hematoma, spinal cord injury, and phrenic nerve palsy caused by inadvertently high anesthetic level, but these never occurred in the authors' experience. Further concerns relate to patient participation in operating room conversations or risk for development of perioperative panic attacks. However, the authors have found that reassuring the patient during the procedure, explaining step-by-step what is being performed, and even showing the ongoing procedure on the operating video can greatly improve the perioperative wellness and expectations of patients, particularly if the procedure is performed for oncologic diseases. Panic attacks occurred in few patients and could be usually managed through

  18. Tissue-specific root ion profiling reveals essential roles of the CAX and ACA calcium transport systems in response to hypoxia in Arabidopsis

    PubMed Central

    Wang, Feifei; Chen, Zhong-Hua; Liu, Xiaohui; Colmer, Timothy David; Zhou, Meixue; Shabala, Sergey

    2016-01-01

    Waterlogging is a major abiotic stress that limits the growth of plants. The crucial role of Ca2+ as a second messenger in response to abiotic and biotic stimuli has been widely recognized in plants. However, the physiological and molecular mechanisms of Ca2+ distribution within specific cell types in different root zones under hypoxia is poorly understood. In this work, whole-plant physiological and tissue-specific Ca2+ changes were studied using several ACA (Ca2+-ATPase) and CAX (Ca2+/proton exchanger) knock-out Arabidopsis mutants subjected to waterlogging treatment. In the wild-type (WT) plants, several days of hypoxia decreased the expression of ACA8, CAX4, and CAX11 by 33% and 50% compared with the control. The hypoxic treatment also resulted in an up to 11-fold tissue-dependent increase in Ca2+ accumulation in root tissues as revealed by confocal microscopy. The increase was much higher in stelar cells in the mature zone of Arabidopsis mutants with loss of function for ACA8, ACA11, CAX4, and CAX11. In addition, a significantly increased Ca2+ concentration was found in the cytosol of stelar cells in the mature zone after hypoxic treatment. Three weeks of waterlogging resulted in dramatic loss of shoot biomass in cax11 plants (67% loss in shoot dry weight), while in the WT and other transport mutants this decline was only 14–22%. These results were also consistent with a decline in leaf chlorophyll fluorescence (F v/F m). It is suggested that CAX11 plays a key role in maintaining cytosolic Ca2+ homeostasis and/or signalling in root cells under hypoxic conditions. PMID:26889007

  19. Deep RNA-Seq profile reveals biodiversity, plant-microbe interactions and a large family of NBS-LRR resistance genes in walnut (Juglans regia) tissues.

    PubMed

    Chakraborty, Sandeep; Britton, Monica; Martínez-García, P J; Dandekar, Abhaya M

    2016-03-01

    Deep RNA-Seq profiling, a revolutionary method used for quantifying transcriptional levels, often includes non-specific transcripts from other co-existing organisms in spite of stringent protocols. Using the recently published walnut genome sequence as a filter, we present a broad analysis of the RNA-Seq derived transcriptome profiles obtained from twenty different tissues to extract the biodiversity and possible plant-microbe interactions in the walnut ecosystem in California. Since the residual nature of the transcripts being analyzed does not provide sufficient information to identify the exact strain, inferences made are constrained to the genus level. The presence of the pathogenic oomycete Phytophthora was detected in the root through the presence of a glyceraldehyde-3-phosphate dehydrogenase. Cryptococcus, the causal agent of cryptococcosis, was found in the catkins and vegetative buds, corroborating previous work indicating that the plant surface supported the sexual cycle of this human pathogen. The RNA-Seq profile revealed several species of the endophytic nitrogen fixing Actinobacteria. Another bacterial species implicated in aerobic biodegradation of methyl tert-butyl ether (Methylibium petroleiphilum) is also found in the root. RNA encoding proteins from the pea aphid were found in the leaves and vegetative buds, while a serine protease from mosquito with significant homology to a female reproductive tract protease from Drosophila mojavensis in the vegetative bud suggests egg-laying activities. The comprehensive analysis of RNA-seq data present also unraveled detailed, tissue-specific information of ~400 transcripts encoded by the largest family of resistance (R) genes (NBS-LRR), which possibly rationalizes the resistance of the specific walnut plant to the pathogens detected. Thus, we elucidate the biodiversity and possible plant-microbe interactions in several walnut (Juglans regia) tissues in California using deep RNA-Seq profiling.

  20. Recurrent Intrathoracic Locking of the Scapula after Lung Cancer Resection and Combined Rib Resection

    PubMed Central

    Kimura, Akinori; Ajiki, Takashi; Sekiya, Hitoshi; Takeshita, Katsushi

    2017-01-01

    We report a case of recurrent locking of the scapula in the thorax after combined lobectomy and thoracic wall resection for advanced lung cancer. The patient was a 52-year-old man with advanced spindle cell carcinoma in his right lung. He had undergone right lung lobectomy and thoracic wall excision (Th1–5). Intrathoracic repair had not been performed to address the defect in the thoracic wall. Two months after the operation he experienced sudden acute pain in the right shoulder. Three-dimensional computed tomography revealed locking of the scapula intrathoracically. The diagnosis was recurrent locking of the scapula in the thorax. He underwent conservative treatment. Because his symptoms were not alleviated and he continued to experience recurrent locking, we performed partial resection of the inferior part of the scapula. Although scapular locking diminished after this procedure, there were still some pain and “catching” between the scapula and the thoracic wall (T6) when he undertook certain movements. No further surgery could be performed, however, because the cancer from the primary lesion had recurred near the previously operated thoracic wall. A procedure for recurrent intrathoracic locking of the scapula was not successful in this case. PMID:28348908

  1. [Morphological results of repeated transurethral resection of the bladder for muscle-non-invasive cancer].

    PubMed

    Seregin, I V; Seregin, A V; Dadashev, É O; Polozhentsev, O B; Loran, O B

    2013-01-01

    Operating material taken from 101 patients aged 32 to 88 years with verified bladder cancer was investigated. Repeated morphological analysis of biopsy material obtained after repeated transurethral resection (TUR) has revealed 35.6% of residual tumors, and the same stage cancer was diagnosed in 23% of cases, lower stage Ta cancer--in 5% of cases. Underestimating the stage took place in 7.9% of cases. Residual tumors according to histological examination were revealed in 24.7% of patients. In tumor size larger than 3 cm, the frequency of detection of residual tumors and muscular invasion was 44.8 and 12.1%, and in tumor size less than 3 cm--23.2 and 2.3%, respectively. Residual tumor was found in 45.7% of cases with rT1G3 and in 27.2% of cases with rT1G2. The muscle invasion was observed only in low-grade tumors--13.5% of cases. In the presence of muscular tissue, invasion was diagnosed in 1.4% of cases, and in the absence of muscular tissue--in 20.5%. Repeated TUR of bladder for muscles-non-invasive cancer allows achieving optimal local control, obtaining additional histological material for morphological examination to confirm the stage of the disease, there from, choose the appropriate treatment and remove residual tumor.

  2. Global Analysis of DNA Methylation Variation in Adipose Tissue from Twins Reveals Links to Disease-Associated Variants in Distal Regulatory Elements

    PubMed Central

    Grundberg, Elin; Meduri, Eshwar; Sandling, Johanna K.; Hedman, Åsa K.; Keildson, Sarah; Buil, Alfonso; Busche, Stephan; Yuan, Wei; Nisbet, James; Sekowska, Magdalena; Wilk, Alicja; Barrett, Amy; Small, Kerrin S.; Ge, Bing; Caron, Maxime; Shin, So-Youn; Ahmadi, Kourosh R.; Ainali, Chrysanthi; Barrett, Amy; Bataille, Veronique; Bell, Jordana T.; Buil, Alfonso; Deloukas, Panos; Dermitzakis, Emmanouil T.; Dimas, Antigone S.; Durbin, Richard; Glass, Daniel; Grundberg, Elin; Hassanali, Neelam; Hedman, Åsa K.; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lindgren, Cecilia M.; Lowe, Christopher E.; McCarthy, Mark I.; Meduri, Eshwar; di Meglio, Paola; Min, Josine L.; Montgomery, Stephen B.; Nestle, Frank O.; Nica, Alexandra C.; Nisbet, James; O’Rahilly, Stephen; Parts, Leopold; Potter, Simon; Sandling, Johanna; Sekowska, Magdalena; Shin, So-Youn; Small, Kerrin S.; Soranzo, Nicole; Spector, Tim D.; Surdulescu, Gabriela; Travers, Mary E.; Tsaprouni, Loukia; Tsoka, Sophia; Wilk, Alicja; Yang, Tsun-Po; Zondervan, Krina T.; Lathrop, Mark; Dermitzakis, Emmanouil T.; McCarthy, Mark I.; Spector, Timothy D.; Bell, Jordana T.; Deloukas, Panos

    2013-01-01

    Epigenetic modifications such as DNA methylation play a key role in gene regulation and disease susceptibility. However, little is known about the genome-wide frequency, localization, and function of methylation variation and how it is regulated by genetic and environmental factors. We utilized the Multiple Tissue Human Expression Resource (MuTHER) and generated Illumina 450K adipose methylome data from 648 twins. We found that individual CpGs had low variance and that variability was suppressed in promoters. We noted that DNA methylation variation was highly heritable (h2median = 0.34) and that shared environmental effects correlated with metabolic phenotype-associated CpGs. Analysis of methylation quantitative-trait loci (metQTL) revealed that 28% of CpGs were associated with nearby SNPs, and when overlapping them with adipose expression quantitative-trait loci (eQTL) from the same individuals, we found that 6% of the loci played a role in regulating both gene expression and DNA methylation. These associations were bidirectional, but there were pronounced negative associations for promoter CpGs. Integration of metQTL with adipose reference epigenomes and disease associations revealed significant enrichment of metQTL overlapping metabolic-trait or disease loci in enhancers (the strongest effects were for high-density lipoprotein cholesterol and body mass index [BMI]). We followed up with the BMI SNP rs713586, a cg01884057 metQTL that overlaps an enhancer upstream of ADCY3, and used bisulphite sequencing to refine this region. Our results showed widespread population invariability yet sequence dependence on adipose DNA methylation but that incorporating maps of regulatory elements aid in linking CpG variation to gene regulation and disease risk in a tissue-dependent manner. PMID:24183450

  3. Protease analysis by neoepitope approach reveals the activation of MMP-9 is achieved proteolytically in a test tissue cartilage model involved in bone formation.

    PubMed

    Lee, Eunice R; Lamplugh, Lisa; Kluczyk, Beata; Mort, John S; Leblond, Charles Philippe

    2006-09-01

    A principle of regulation of matrix metalloproteinase (MMP) activity has been introduced as the cysteine-switch mechanism of activation (Springman et al. 1990). According to this mechanism, a critical Cys residue found in the auto-inhibitory propeptide domain of latent proenzyme is important to determine whether or not activation is turned on or off. The mechanism further allows for multiple modes of activation. To determine whether or not activation is accomplished proteolytically within a rat test cartilage model, protease analysis by the neoepitope approach, which relies upon a set of antibodies, was applied. One is used to identify the MMP-9 proenzyme bearing the critical cysteine residue, the other to identify any enzyme present bearing a new NH2-terminus 89FQTFD. This is indicative of MMP-9 lacking the cysteine switch. The antibody set has been applied to frozen tissue sections and analyzed by light and electron microscopic methods. Results reveal that activation of the MMP-9 protease involves limited proteolysis resulting in propeptide domain release. Here we report the observed changes of protease form to indigenous cells and extracellular matrix, thereby making it possible to uncover the features of MMP-9 activation within a specified set of tissue circumstances where a cartilage model is transformed into definitive bone. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

  4. Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue.

    PubMed

    Zheng, J; Ibrahim, S; Petersen, F; Yu, X

    2012-12-01

    Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between PTPN22 polymorphism C1858T and autoimmune diseases. The results showed a remarkable pattern; PTPN22 C1858T was strongly associated with type I diabetes, rheumatoid arthritis, immune thrombocytopenia, generalized vitiligo with concomitant autoimmune diseases, idiopathic inflammatory myopathies, Graves' disease, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitis and Addison's disease. By contrast, PTPN22 C1858T showed a negligible association with systemic sclerosis, celiac disease, multiple sclerosis, psoriasis, ankylosing spondylitis, pemphigus vulgaris, ulcerative colitis, primary sclerosing cholangitis, primary biliary cirrhosis, Crohn's disease and acute anterior uveitis. Further analysis revealed a clear distinction between the two groups of diseases with regard to their targeted tissues: most autoimmune diseases showing an insignificant association with PTPN22 C1858T manifest in skin, the gastrointestinal tract or in immune privileged sites. These results showed that the association of PTPN22 polymorphism with autoimmune diseases depends on the localization of the affected tissue, suggesting a role of targeted organ variation in the disease manifestations.

  5. Small-bowel resection for metastatic melanoma

    PubMed Central

    Al-Sheneber, Ibrahim F.; Meterissian, Sarkis H.; Loutfi, Antoine; Watters, A. Kevin; Shibata, Henry R.

    1996-01-01

    Objective To determine whether complete resection of small-bowel metastases from melanoma improves patient survival. Design A computer-aided chart review. Setting Hospitals associated with McGill University. Patients Twenty patients (17 men, 3 women), identified from 1524 patients with melanoma, who underwent surgery to the small bowel for metastases. Patient age and clinical presentation, tumour site and stage were recorded. Intervention Exploratory laparotomy with complete or partial resection of involved small bowel. Main Outcome Measures Operative morbidity, mortality and length of survival related to the extent of small-bowel resection. Results Eleven patients had complete resection, 8 patients had partial resection and 1 patient had a palliative bypass only. Long-term survival (ranging from 2 to 10 years) was 36% in those who had complete resection and 0% in those who had partial resection; operative morbidity and mortality were 20% and 15% respectively. Conclusion Complete resection of small-bowel metastases in patients with metastatic melanoma can result in long-term survival. PMID:8640618

  6. Anaesthetic management in thoracoscopic distal tracheal resection.

    PubMed

    Acosta Martínez, J; Beato López, J; Domínguez Blanco, A; López Romero, J L; López Villalobos, J L

    2017-03-01

    Surgical resection of tracheal tumours, especially distal tracheal tumours, is a challenge for the anaesthesiologists involved, mainly due to difficulties in ensuring adequate control of the airway and ventilation. We report the case of a patient undergoing tracheal resection and anastomosis by VATS, emphasizing the anaesthetic management.

  7. Advances in the Surgical Management of Resectable and Borderline Resectable Pancreas Cancer.

    PubMed

    Helmink, Beth A; Snyder, Rebecca A; Idrees, Kamran; Merchant, Nipun B; Parikh, Alexander A

    2016-04-01

    Successful surgical resection offers the only chance for cure in patients with pancreatic cancer. However, pancreatic resection is feasible in less than 20% of the patients. In this review, the current state of surgical management of pancreatic cancer is discussed. The definition of resectability based on cross-sectional imaging and the technical aspects of surgery, including vascular resection and/or reconstruction, management of aberrant vascular anatomy and extent of lymphadenectomy, are appraised. Furthermore, common pancreatic resection-specific postoperative complications and their management are reviewed.

  8. Gut hormone release after intestinal resection.

    PubMed Central

    Besterman, H S; Adrian, T E; Mallinson, C N; Christofides, N D; Sarson, D L; Pera, A; Lombardo, L; Modigliani, R; Bloom, S R

    1982-01-01

    To investigate the possible role of gut and pancreatic hormones in the adaptive responses to gut resection, plasma concentrations of the circulating hormones were measured, in response to a test breakfast, in patients with either small or large intestinal resection and in healthy control subjects. In 18 patients with partial ileal resection a significant threefold rise was found in basal and postprandial levels of pancreatic polypeptide, a fourfold increase in motilin, and more than a twofold increase in gastrin and enteroglucagon levels compared with healthy controls. In contrast, nine patients with colonic resection had a threefold rise in levels of pancreatic polypeptide only. One or more of these peptides may have a role in stimulating the adaptive changes found after gut resection. PMID:7117905

  9. Pancreatic Ductal Adenocarcinoma is Spread to the Peripancreatic Soft Tissue in the Majority of Resected Cases, Rendering the AJCC T-Stage Protocol (7th Edition) Inapplicable and Insignificant: A Size-Based Staging System (pT1: ≤2, pT2: >2–≤4, pT3: >4 cm) is More Valid and Clinically Relevant

    PubMed Central

    Saka, Burcu; Balci, Serdar; Basturk, Olca; Bagci, Pelin; Postlewait, Lauren M.; Maithel, Shishir; Knight, Jessica; El-Rayes, Bassel; Kooby, David; Sarmiento, Juan; Muraki, Takashi; Oliva, Irma; Bandyopadhyay, Sudeshna; Akkas, Gizem; Goodman, Michael; Reid, Michelle D.; Krasinskas, Alyssa; Everett, Rhonda; Adsay, Volkan

    2016-01-01

    Background Most studies have failed to identify any prognostic value of the current T-stage protocol for pancreatic ductal adenocarcinoma (PDAC) by the American Joint Committee on Cancer and the Union for International Cancer Control unless some grouping was performed. Methods To document the parameters included in this T-stage protocol, 223 consecutive pancreatoduodenectomy specimens with PDAC were processed by a uniform grossing protocol. Results Peripancreatic soft tissue (PST) involvement, the main pT3 parameter, was found to be inapplicable and irreproducible due to lack of a true capsule in the pancreas and variability in the amount and distribution of adipose tissue. Furthermore, 91 % of the cases showed carcinoma in the adipose tissue, presumably representing the PST, and thus were classified as pT3. An additional 4.5 % were qualified as pT3 due to extension into adjacent sites. The T-stage defined as such was not found to have any correlation with survival (p = 0.4). A revised T-stage protocol was devised that defined pT1 as 2 cm or smaller, pT2 as >2–4 cm, and pT3 as larger than 4 cm. This revised protocol was tested in 757 consecutive PDACs. The median and 3-year survival rates of this size-based protocol were 26, 18, 13 months, and 40 %, 26 %, 20 %, respectively (p < 0.0001). The association between higher T-stage and shorter survival persisted in N0 cases and in multivariate modeling. Analysis of the Surveillance, Epidemiology, and End Results database also confirmed the survival differences (p < 0.0001). Conclusions This study showed that resected PDACs are already spread to various surfaces of the pancreas, leaving only about 4 % of PDACs to truly qualify as pT1/T2, and that the current T-stage protocol does not have any prognostic correlation. In contrast, as shown previously in many studies, size is an important prognosticator, and a size-based T-stage protocol is more applicable and has prognostic value in PDAC. PMID:26832882

  10. Colon resection for ovarian cancer: intraoperative decisions.

    PubMed

    Hoffman, Mitchel S; Zervose, Emmanuel

    2008-11-01

    To discuss the benefits and morbidity of and indications for colon resection during cytoreductive operations for ovarian cancer. The history of cytoreductive surgery for ovarian cancer is discussed, with special attention to the incorporation of colon resection. Literature regarding cytoreductive surgery for ovarian cancer is then reviewed, again with attention to the role of colon resection. The focus of the review is directed at broad technical considerations and rationales, for both primary and secondary cytoreduction. Over the past 15 to 20 years the standard cytoreductive operation for ovarian cancer has shifted from an abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy to an en bloc radical resection of the pelvic tumor and an omentectomy, and more recently to include increasing use of extensive upper abdominal surgery. En bloc pelvic resection frequently includes rectosigmoid resection, almost always accompanied by a primary anastomosis. Other portions of the colon are at risk for metastatic involvement and sometimes require resection in order to achieve optimal cytoreduction. The data regarding colon resection for the purpose of surgical cytoreduction of ovarian cancer are conflicting (in terms of benefit) and all retrospective. However, the preponderance of information supports a benefit in terms of survival when cytoreduction is clearly optimal. Similar to primary surgery, benefit from secondary cytoreduction of ovarian cancer occurs when only a small volume of disease is left behind. The preponderance of data suggests that colon resection to achieve optimal cytoreduction has a positive impact on survival. In order to better understand the role of colon resection as well as other extensive cytoreductive procedures for ovarian cancer, it will be important to continue to improve our understanding of prognostic variables such as the nuances of metastatic bowel involvement in order to better guide appropriate surgical management.

  11. Optical assessment of tumor resection margins in the breast

    PubMed Central

    Brown, J. Quincy; Bydlon, Torre M.; Richards, Lisa M.; Yu, Bing; Kennedy, Stephanie A.; Geradts, Joseph; Wilke, Lee G.; Junker, Marlee; Gallagher, Jennifer; Barry, William; Ramanujam, Nimmi

    2011-01-01

    Breast conserving surgery, in which the breast tumor and surrounding normal tissue are removed, is the primary mode of treatment for invasive and in situ carcinomas of the breast, conditions that affect nearly 200,000 women annually. Of these nearly 200,000 patients who undergo this surgical procedure, between 20–70% of them may undergo additional surgeries to remove tumor that was left behind in the first surgery, due to the lack of intra-operative tools which can detect whether the boundaries of the excised specimens are free from residual cancer. Optical techniques have many attractive attributes which may make them useful tools for intra-operative assessment of breast tumor resection margins. In this manuscript, we discuss clinical design criteria for intra-operative breast tumor margin assessment, and review optical techniques appied to this problem. In addition, we report on the development and clinical testing of quantitative diffuse reflectance imaging (Q-DRI) as a potential solution to this clinical need. Q-DRI is a spectral imaging tool which has been applied to 56 resection margins in 48 patients at Duke University Medical Center. Clear sources of contrast between cancerous and cancer-free resection margins were identified with the device, and resulted in an overall accuracy of 75% in detecting positive margins. PMID:21544237

  12. Laser dosimetry planning tool for colonoscopic tumor resection

    NASA Astrophysics Data System (ADS)

    Pelayo-Fernández, M. L.; Fanjul-Vélez, F.; Salas-García, I.; Zverev, M.; Arce-Diego, J. L.

    2016-03-01

    Gastrointestinal tumoral pathologies are quite common nowadays. Diseases such as gastric antral vascular ectasia (GAVE) or actinic proctitis may require endoscopic surgery. Argon Plasma Coagulated (APC) or radiofrequency are usually employed. However, they present disadvantages, such as the reduced treated area, magnetic resonance incompatibility, or an uncontrolled ablation depth. Optical surgery could avoid these problems and contribute to a better and controlled treatment result, either ablative or coagulative, in a minimally invasive, non-contact and non-ionizing way. The treatment area could also be increased by adequate optical fiber probe design. In this work laser surgery is analyzed for resection of colonic tumors. A Monte Carlo model is employed to study optical propagation, and an optical ablation approach allows the estimation of the resected volume. The ablation approach is based on plasma-induced ablation, particularly taking into account the freeelectron density generated in the tissue by the pulsed optical source. Several wavelengths, radii and malignant tissue types are considered, either healthy, adenomatous or even coagulated tissues. Optimum source parameters as a function of tumor geometry can be estimated for treatment planning.

  13. Resection arthroplasty of the hip in paralytic dislocations.

    PubMed

    Kalen, V; Gamble, J G

    1984-06-01

    The chronically dislocated paralytic hip causes postural difficulties, nursing and hygiene problems, and pain. Therapeutic options are limited. This study reviews the results of resection arthroplasty on 18 hips of 15 such patients. This procedure has many complications, including hip ankylosis, heterotopic ossification, abduction contracture and bony overgrowth. Despite this, all of the nursing goals were achieved and most patients had relief of pain. The operation is most successful in the skeletally mature patients, and it relies on soft-tissue interposition between the bony fragments and postoperative positioning to ensure optimum posture.

  14. Indications and interventional options for non-resectable tracheal stenosis

    PubMed Central

    Bacon, Jenny Louise; Patterson, Caroline Marie

    2014-01-01

    Non-specific presentation and normal examination findings in early disease often result in tracheal obstruction being overlooked as a diagnosis until patients present acutely. Once diagnosed, surgical options should be considered, but often patient co-morbidity necessitates other interventional options. Non-resectable tracheal stenosis can be successfully managed by interventional bronchoscopy, with therapeutic options including airway dilatation, local tissue destruction and airway stenting. There are common aspects to the management of tracheal obstruction, tracheomalacia and tracheal fistulae. This paper reviews the pathogenesis, presentation, investigation and management of tracheal disease, with a focus on tracheal obstruction and the role of endotracheal intervention in management. PMID:24624290

  15. Detection of unsuspected ovarian pregnancy by wedge resection

    PubMed Central

    Helde, M. D.; Campbell, J. S.; Himaya, A.; Nuyens, J. J.; Cowley, F. C.; Hurteau, G. D.

    1972-01-01

    Five follicular ovarian implantations occurred among 200 ectopic pregnancies encountered during a 14-year period. Abortions from impregnated follicles may cause hemoperitoneum more often than is generally suspected. Wedge resection or cystectomy to ensure hemostasis provides tissue for histological examination, without which ruptured ovarian pregnancy may masquerade as rupture of a corpus luteum with hemorrhage (“ovarian apoplexy”). Including patients reported here, IUCD users have within the past five years accounted for about 10% of all ovarian pregnancies recorded in English. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:5057958

  16. Image updating for brain deformation compensation in tumor resection

    NASA Astrophysics Data System (ADS)

    Fan, Xiaoyao; Ji, Songbai; Olson, Jonathan D.; Roberts, David W.; Hartov, Alex; Paulsen, Keith D.

    2016-03-01

    Preoperative magnetic resonance images (pMR) are typically used for intraoperative guidance in image-guided neurosurgery, the accuracy of which can be significantly compromised by brain deformation. Biomechanical finite element models (FEM) have been developed to estimate whole-brain deformation and produce model-updated MR (uMR) that compensates for brain deformation at different surgical stages. Early stages of surgery, such as after craniotomy and after dural opening, have been well studied, whereas later stages after tumor resection begins remain challenging. In this paper, we present a method to simulate tumor resection by incorporating data from intraoperative stereovision (iSV). The amount of tissue resection was estimated from iSV using a "trial-and-error" approach, and the cortical shift was measured from iSV through a surface registration method using projected images and an optical flow (OF) motion tracking algorithm. The measured displacements were employed to drive the biomechanical brain deformation model, and the estimated whole-brain deformation was subsequently used to deform pMR and produce uMR. We illustrate the method using one patient example. The results show that the uMR aligned well with iSV and the overall misfit between model estimates and measured displacements was 1.46 mm. The overall computational time was ~5 min, including iSV image acquisition after resection, surface registration, modeling, and image warping, with minimal interruption to the surgical flow. Furthermore, we compare uMR against intraoperative MR (iMR) that was acquired following iSV acquisition.

  17. Laparoscopic liver resection: Experience based guidelines.

    PubMed

    Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirola; Fonseca, Gilton Marques; Araújo, Raphael Leonardo Cunha; Jeismann, Vagner Birk; Perini, Marcos Vinícius; Lupinacci, Renato Micelli; Cecconello, Ivan; Herman, Paulo

    2016-01-27

    Laparoscopic liver resection (LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and operations increased in frequency and complexity. Evidence supporting LLR comes from case-series, comparative studies and meta-analysis. Despite lack of level 1 evidence, the body of literature is stronger and existing data confirms the safety, feasibility and benefits of laparoscopic approach when compared to open resection. Indications for LLR do not differ from those for open surgery. They include benign and malignant (both primary and metastatic) tumors and living donor liver harvesting. Currently, resection of lesions located on anterolateral segments and left lateral sectionectomy are performed systematically by laparoscopy in hepatobiliary specialized centers. Resection of lesions located on posterosuperior segments (1, 4a, 7, 8) and major liver resections were shown to be feasible but remain technically demanding procedures, which should be reserved to experienced surgeons. Hand-assisted and laparoscopy-assisted procedures appeared to increase the indications of minimally invasive liver surgery and are useful strategies applied to difficult and major resections. LLR proved to be safe for malignant lesions and offers some short-term advantages over open resection. Oncological results including resection margin status and long-term survival were not inferior to open resection. At present, surgical community expects high quality studies to base the already perceived better outcomes achieved by laparoscopy in major centers' practice. Continuous surgical training, as well as new technologies should augment the application of laparoscopic liver surgery. Future applicability of new technologies such as robot assistance and image-guided surgery is still under investigation.

  18. Liver Resections for Metastases from Intraabdominal Leiomyosarcoma

    PubMed Central

    Pereira, Bianca De Lourdes; Brenner, Marcia Cristina Lima; Pereira-Lima, Luiz

    1999-01-01

    This paper discusses liver resection for intraabdominal leiomyosarcoma metastases as a therapy for carefully selected patients. Of the 83 hepatectomies performed from 1992 to 1996, five were resections for liver metastases due to intraabdominal leiomyosarcoma, in 3 patients. The surgical indication was single liver metastases, without any evidence of extrahepatic disease. No mortality occurred during surgery and the longest survival was 38 months. We concluded that liver resection for leiomyosarcoma metastases can be performed, allowing a long term survival in an occasional patient. PMID:10468118

  19. [A case of adenocarcinoma occurring at colostomy site 7 years after abdominoperineal resection for rectal cancer resected after preoperative mFOLFOX6 chemotherapy].

    PubMed

    Hata, Tatsuo; Tsuruta, Yoshihiko; Takamori, Shigeru; Shishikura, Yuri

    2012-09-01

    A 78-year-old man had undergone abdominoperineal resection for rectal cancer in 2003. After 7 years, he visited our hospital with complaints of turbid discharge from the stoma. A tumor 11 cm in diameter was shown at the site of the stoma. A partial resected biopsy revealed moderately-differentiated adenocarcinoma. We diagnosed metachronous multiple carcinoma or recurrent cancer at the colostomy site. After loop colostomy of the ascending colon was performed, systemic chemotherapy with mFOLFOX6 was performed. After 5 courses, the tumor revealed a significant reduction in its size. Afterwards, the stoma including the tumor and remaining left-side colon with adjacent abdominal wall was resected, keeping the surgical margin free. In the resected specimen, histological evaluation of the treatment with chemotherapy was assessed to be Grade 1a. As a result of preoperative chemotherapy, we finally were able to resect the minimal area of the adjacent skin and abdominal wall, and succeed in primary closure of the surgical wound. This case suggests that preoperative chemotherapy is a good option for treating cancer occurring at a colostomy site.

  20. Endoscopic transchoroidal and transforaminal approaches for resection of third ventricular colloid cysts.

    PubMed

    Ibáñez-Botella, G; Domínguez, M; Ros, B; De Miguel, L; Márquez, B; Arráez, M A

    2014-04-01

    To review our experience over 10 years in endoscopic resection of third ventricular colloid cysts, describing the details of the transventricular-transchoroidal approach used in selected patients. This series included 24 patients with colloid cysts of the third ventricle treated in our department between October 2001 and January 2013 using an endoscopic approach. Clinical presentation, preoperative radiological findings, endoscopic technique employed, and complications were assessed in all patients. The mean length of patient follow-up was 5.16 years. The most common symptom was headache (75%). The average size of the resected colloid cysts was 16.25 mm, the maximum diameter measured in cranial magnetic resonance imaging. Resection was transforaminal in 16 cases (66.7%), transchoroidal in 7 (29.17%), and transseptal in 1; macroscopically complete resection was achieved in 23 of 24 procedures (95.8%). Complications included three intraventricular hemorrhages, four memory deficits (two of them transient), one case of temporary potomania, two soft tissue infections, and one meningitis. There were no statistically significant differences between the route of resection and number of complications. The Glasgow Outcome Scale at 1 year after surgery was 5 in 82.6% of the patients. A transventricular endoscopic approach allows macroscopically complete resection of third ventricle colloid cysts in most cases. The option of opening the choroidal fissure (transventricular-transchoroidal approach) during the procedure can address third ventricle colloid cysts that do not emerge sufficiently through the foramen of Monro without increasing procedure-related morbidity.

  1. Gene targeting study reveals unexpected expression of brain-expressed X-linked 2 in endocrine and tissue stem/progenitor cells in mice.

    PubMed

    Ito, Keiichi; Yamazaki, Satoshi; Yamamoto, Ryo; Tajima, Yoko; Yanagida, Ayaka; Kobayashi, Toshihiro; Kato-Itoh, Megumi; Kakuta, Shigeru; Iwakura, Yoichiro; Nakauchi, Hiromitsu; Kamiya, Akihide

    2014-10-24

    Identification of genes specifically expressed in stem/progenitor cells is an important issue in developmental and stem cell biology. Genome-wide gene expression analyses in liver cells performed in this study have revealed a strong expression of X-linked genes that include members of the brain-expressed X-linked (Bex) gene family in stem/progenitor cells. Bex family genes are expressed abundantly in the neural cells and have been suggested to play important roles in the development of nervous tissues. However, the physiological role of its individual members and the precise expression pattern outside the nervous system remain largely unknown. Here, we focused on Bex2 and examined its role and expression pattern by generating knock-in mice; the enhanced green fluorescence protein (EGFP) was inserted into the Bex2 locus. Bex2-deficient mice were viable and fertile under laboratory growth conditions showing no obvious phenotypic abnormalities. Through an immunohistochemical analysis and flow cytometry-based approach, we observed unique EGFP reporter expression patterns in endocrine and stem/progenitor cells of the liver, pyloric stomach, and hematopoietic system. Although Bex2 seems to play redundant roles in vivo, these results suggest the significance and potential applications of Bex2 in studies of endocrine and stem/progenitor cells.

  2. Mitotic figure counts are significantly overestimated in resection specimens of invasive breast carcinomas.

    PubMed

    Lehr, Hans-Anton; Rochat, Candice; Schaper, Cornelia; Nobile, Antoine; Shanouda, Sherien; Vijgen, Sandrine; Gauthier, Arnaud; Obermann, Ellen; Leuba, Susana; Schmidt, Marcus; C, Curzio Ruegg; Delaloye, Jean-Francois; Simiantonaki, Nectaria; Schaefer, Stephan C

    2013-03-01

    Several authors have demonstrated an increased number of mitotic figures in breast cancer resection specimen when compared with biopsy material. This has been ascribed to a sampling artifact where biopsies are (i) either too small to allow formal mitotic figure counting or (ii) not necessarily taken form the proliferating tumor periphery. Herein, we propose a different explanation for this phenomenon. Biopsy and resection material of 52 invasive ductal carcinomas was studied. We counted mitotic figures in 10 representative high power fields and quantified MIB-1 immunohistochemistry by visual estimation, counting and image analysis. We found that mitotic figures were elevated by more than three-fold on average in resection specimen over biopsy material from the same tumors (20±6 vs 6±2 mitoses per 10 high power fields, P=0.008), and that this resulted in a relative diminution of post-metaphase figures (anaphase/telophase), which made up 7% of all mitotic figures in biopsies but only 3% in resection specimen (P<0.005). At the same time, the percentages of MIB-1 immunostained tumor cells among total tumor cells were comparable in biopsy and resection material, irrespective of the mode of MIB-1 quantification. Finally, we found no association between the size of the biopsy material and the relative increase of mitotic figures in resection specimen. We propose that the increase in mitotic figures in resection specimen and the significant shift towards metaphase figures is not due to a sampling artifact, but reflects ongoing cell cycle activity in the resected tumor tissue due to fixation delay. The dwindling energy supply will eventually arrest tumor cells in metaphase, where they are readily identified by the diagnostic pathologist. Taken together, we suggest that the rapidly fixed biopsy material better represents true tumor biology and should be privileged as predictive marker of putative response to cytotoxic chemotherapy.

  3. Role of Adjuvant Chemoradiotherapy for Resected Extrahepatic Biliary Tract Cancer

    SciTech Connect

    Kim, Tae Hyun; Han, Sung-Sik; Park, Sang-Jae Lee, Woo Jin; Woo, Sang Myung; Moon, Sung Ho; Yoo, Tae; Kim, Sang Soo; Kim, Seong Hoon; Hong, Eun Kyung; Kim, Dae Yong; Park, Joong-Won

    2011-12-01

    Purpose: To evaluate the effect of adjuvant chemoradiotherapy (CRT) on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for patients with extrahepatic biliary tract cancer treated with curative resection. Methods and Materials: The study involved 168 patients with extrahepatic biliary tract cancer undergoing curative resection between August 2001 and April 2009. Of the 168 patients, 115 received adjuvant CRT (CRT group) and 53 did not (no-CRT group). Gender, age, tumor size, histologic differentiation, pre- and postoperative carbohydrate antigen 19-9 level, resection margin, vascular invasion, perineural invasion, T stage, N stage, overall stage, and the use of adjuvant CRT were analyzed to identify the prognostic factors associated with LRC, DFS, and OS. Results: For all patients, the 5-year LRC, DFS, and OS rate was 54.8%, 30.6%, and 33.9%, respectively. On univariate analysis, the 5-year LRC, DFS, and OS rates in the CRT group were significantly better than those in the no-CRT group (58.5% vs. 44.4%, p = .007; 32.1% vs. 26.1%, p = .041; 36.5% vs. 28.2%, p = .049, respectively). Multivariate analysis revealed that adjuvant CRT was a significant independent prognostic factor for LRC, DFS, and OS (p < .05). Conclusion: Our results have suggested that adjuvant CRT helps achieve LRC and, consequently, improves DFS and OS in patients with extrahepatic biliary tract cancer.

  4. ACR Appropriateness Criteria on Resectable Rectal Cancer

    SciTech Connect

    Suh, W. Warren; Konski, Andre A.; Mohiuddin, Mohammed; Poggi, Matthew M.; Regine, William F.; Cosman, Bard C.; Saltz, Leonard; Johnstone, Peter A.S.

    2008-04-01

    The American College of Radiology (ACR) Appropriateness Criteria on Resectable Rectal Cancer was updated by the Expert Panel on Radiation Oncology-Rectal/Anal Cancer, based on a literature review completed in 2007.

  5. Optimizing Adjuvant Therapy for Resected Pancreatic Cancer

    Cancer.gov

    In this clinical trial, patients with resected pancreatic head cancer will be randomly assigned to receive either gemcitabine with or without erlotinib for 5 treatment cycles. Patients who do not experience disease progression or recurrence will then be r

  6. A cluster of Teflon pledgets manifesting as an intrathoracic cavitary mass following lung resection.

    PubMed

    Lee, J-I; Park, K-Y; Park, C-H

    2010-06-01

    Teflon pledgets are widely used for hemostasis and the reinforcement of friable tissue in surgery. However, rare but serious complications caused by the erosion of Teflon pledgets have been reported. We present an unusual case of an intrathoracic cavitary mass that was formed by the erosion of a cluster of Teflon pledgets into the lung parenchyma eight years after a lung resection.

  7. Endoscopic Resection and Radiofrequency Ablation for Early Esophageal Neoplasia

    PubMed Central

    Belghazi, Kamar; Bergman, Jacques; Pouw, Roos E.

    2016-01-01

    Background In the last few decades, endoscopic treatment of early neoplastic lesions in the esophagus has established itself as a valid and less invasive alternative to surgical resection. Endoscopic resection (ER) is the cornerstone of endoscopic therapy. Next to the curative potential of ER, by removing neoplastic lesions, ER may also serve as a diagnostic tool. The relatively large tissue specimens obtained with ER enable accurate histological staging of a lesion, allowing for optimal decision-making for further patient management. ER was pioneered in Japan, mainly for the resection of gastric lesions and squamous esophageal neoplasia, and also Western countries have been increasingly implementing ER in the treatment of early gastroesophageal neoplasia, mostly associated with Barrett's esophagus (BE). In BE, however, there is still a risk of metachronous lesions in the remainder of the Barrett's after focal ER. Additional treatment of all Barrett's mucosa is therefore advised. Currently, the most effective method for this is by using radiofrequency ablation (RFA). This review will provide an overview of indications for ER and RFA. Key Messages and Conclusions Endoscopic management of early esophageal neoplasia is a safe and valid alternative to surgery and is nowadays the treatment of choice. ER is the mainstay of endoscopic management of early esophageal neoplasia since it allows for removal of neoplastic lesions and provides a large tissue specimen for histological evaluation. In case of early neoplasia in BE, focal ER should be complemented by eradication of the remaining Barrett's mucosa. RFA has proven to be a safe and effective modality to achieve complete eradication of Barrett's mucosa. PMID:27333327

  8. Cecal Leiomyoma: Can We Attempt Endoscopic Resection?

    PubMed Central

    Badipatla, Kanthi Rekha; Kamireddy, Chandana; Niazi, Masooma; Nayudu, Suresh Kumar

    2016-01-01

    Gastrointestinal leiomyomas are smooth muscle tumors arising from the muscularis mucosae, muscularis propriae and possibly from smooth muscle of the vessel wall. Management depends on the size, location and the clinical scenario. Endoscopic snare cauterization with or without saline lift has been described in literature for tumors involving the left colon. To the best of our knowledge, endoscopic resection of right colon leiomyoma was never attempted in the past. We present a case of cecal leiomyoma which was resected endoscopically. PMID:28058080

  9. [Laparoscopic distal resection of the pancreas].

    PubMed

    Gürlich, R; Sixta, B; Oliverius, M; Kment, M; Rusina, R; Spicák, J; Sváb, J

    2005-09-01

    During the last two years, reports on laparoscopic procedures of the pancreas have been on increase. Laparoscopic resection of the pancreatic cauda is indicated, primarily, for benign cystic lesions of the cauda of the pancreas and for neuroendocrine tumors of the pancreas (mainly insulinomas). We have not recorded any report on the above procedure in the Czech literature. Therefore, in our case review, we have described laparoscopic distal resection of the pancreas with splenectomy for a pseudopapillary tumor of the pancreas.

  10. Resection for oesophageal cancer - complications and survival.

    PubMed

    Grøtting, Marie Sæthre; Løberg, Else Marit; Johannessen, Hans-Olaf; Johnson, Egil

    2016-05-01

    BACKGROUND Surgery is considered necessary to achieve a cure for oesophageal cancer. Minimally invasive oesophageal resection is increasingly performed with the aim of reducing the number of complications compared with open surgery. The purpose of this study was to investigate postoperative complications, mortality and long-term survival following hybrid oesophageal resection by laparoscopy and thoracotomy.MATERIAL AND METHOD Patients with oesophageal cancer who underwent hybrid resection with curative intent at Oslo University Hospital Ullevål from 1 November 2007 to 1 June 2013 were included (n = 109). Complications were graded according to the Clavien-Dindo classification and survival figures were recorded.RESULTS Median age was 65 years, 79 % were men. Altogether 118 complications were recorded in 70 patients (64.2 %). Distribution of complications was 1.8 % for stage I, 29.4 % for stage II, 22.1 % for stage III and 11.0 % for stage IV. Anastomotic leakage occurred in 4.6 %. There was no postoperative mortality. The proportion of R0 resections with microscopic radicality was 91 % (n = 100). For the entire patient population, the estimated 5-year survival rate was 48 % (95 % CI 36 - 60 %), for R0 resection 51 % (38 - 63 %) and for R1-2 resection 0 %. Estimated median survival with R0-2, R0 and R1-2 resection was 55, 55 and 10 months (0 - 28 months), respectively. R status and stage had a significant bearing on survival.INTERPRETATION There was a low percentage of serious complications, no mortality and few anastomotic leakages after hybrid resection for oesophageal cancer. The 5-year survival rate was good.

  11. Fluorescence-Guided Probes of Aptamer-Targeted Gold Nanoparticles with Computed Tomography Imaging Accesses for in Vivo Tumor Resection

    PubMed Central

    Li, Cheng-Hung; Kuo, Tsung-Rong; Su, Hsin-Jan; Lai, Wei-Yun; Yang, Pan-Chyr; Chen, Jinn-Shiun; Wang, Di-Yan; Wu, Yi-Chun; Chen, Chia-Chun

    2015-01-01

    Recent development of molecular imaging probes for fluorescence-guided surgery has shown great progresses for determining tumor margin to execute the tissue resection. Here we synthesize the fluorescent gold nanoparticles conjugated with diatrizoic acid and nucleolin-targeted AS1411 aptamer. The nanoparticle conjugates exhibit high water-solubility, good biocompatibility, visible fluorescence and strong X-ray attenuation for computed tomography (CT) contrast enhancement. The fluorescent nanoparticle conjugates are applied as a molecular contrast agent to reveal the tumor location in CL1-5 tumor-bearing mice by CT imaging. Furthermore, the orange-red fluorescence emitting from the conjugates in the CL1-5 tumor can be easily visualized by the naked eyes. After the resection, the IVIS measurements show that the fluorescence signal of the nanoparticle conjugates in the tumor is greatly enhanced in comparison to that in the controlled experiment. Our work has shown potential application of functionalized nanoparticles as a dual-function imaging agent in clinical fluorescence-guided surgery. PMID:26507179

  12. LAPAROSCOPIC RESECTION OF GASTROINTESTINAL STROMAL TUMORS (GIST)

    PubMed Central

    LOUREIRO, Marcelo de Paula; de ALMEIDA, Rômulo Augusto Andrade; CLAUS, Christiano Marlo Paggi; BONIN, Eduardo Aimoré; CURY-FILHO,, Antônio Moris; DIMBARRE, Daniellson; da COSTA, Marco Aurélio Raeder; VITAL, Marcílio Lisboa

    2016-01-01

    Background Gastrointestinal mesenchymal or stromal tumors (GIST) are lesions originated on digestive tract walls, which are treated by surgical resection. Several laparoscopic techniques, from gastrectomies to segmental resections, have been used successfully. Aim Describe a single center experience on laparoscopic GIST resection. Method Charts of 15 operated patients were retrospectively reviewed. Thirteen had gastric lesions, of which ten were sub epithelial, ranging from 2-8 cm; and three were pure exofitic growing lesions. The remaining two patients had small bowel lesions. Surgical laparoscopic treatment consisted of two distal gastrectomies, 11 wedge gastric resections and two segmental enterectomies. Mechanical suture was used in the majority of patients except on six, which underwent resection and closure using manual absorbable sutures. There were no conversions to open technique. Results Mean operative time was 1h 29 min±92 (40-420 min). Average lenght of hospital stay was three days (2-6 days). There were no leaks, postoperative bleeding or need for reintervention. Mean postoperative follow-up was 38±17 months (6-60 months). Three patients underwent adjuvant Imatinib treatment, one for recurrence five months postoperatively and two for tumors with moderate risk for recurrence . Conclusion Laparoscopic GIST resection, not only for small lesions but also for tumors above 5 cm, is safe and acceptable technique. PMID:27120729

  13. Extralevator abdominoperineal resection in the prone position.

    PubMed

    Flor-Lorente, Blas; Frasson, Matteo; Montilla, Erick

    2014-03-01

    The Miles operation is every day more in the limelight. The abdominoperineal resection compared to anterior resection results in increased rate of circumferential resection margin (CRM) infiltration, increased iatrogenic tumor perforation rate and poorer quality of the mesorectum. These worse results may be caused by excessive dissection between the distal mesorectum and the plane of the levator ani and the consequent "resection waist" or "cone" effect in the specimen. A wider excision of the pelvic floor muscles, known as extraelevator abdominoperineal resection (ELAPE), would provide a "cylindrical" specimen which would hypothetically reduce the risk of tumor perforation and CRM infiltration and local recurrence rate. However, there is insufficient evidence to conclude that the ELAPE is oncologically superior compared to standard abdominoperineal resection. Independently from the surgical technique adopted, another actual point of discussion is the position of the patient during the perineal part of the operation. The position on "prone" provides excellent pelvic exposure, a top-down dissection under direct vision and is very comfortable for the operating surgeons. However, there is no clear scientific evidence of the superiority of prone ELAPE over supine ELAPE in terms of oncologic results, morbidity and mortality. The laparoscopy seems to be the best surgical approach for the abdominal part of the operation, although it has not been validated so far by large prospective studies. Prospective, controlled and randomized trials are necessary to resolve all these issues. The current interest in a more accurate and standardized perineal surgery to obtain a cylindrical specimen, undoubtedly, will improve results.

  14. Liver resection for intermediate hepatocellular carcinoma

    PubMed Central

    Yi, Peng-Sheng; Zhang, Ming; Zhao, Ji-Tong; Xu, Ming-Qing

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. The Barcelona Clinic Liver Cancer (BCLC) staging system is regarded as the gold standard staging system for HCC, classifying HCC as early, intermediate, or advanced. For intermediate HCC, trans-catheter arterial chemoembolization (TACE) is recommended as the optimal strategy by the BCLC guideline. This review investigates whether liver resection is better than TACE for intermediate HCC. Based on published studies, we compare the survival benefits and complications of liver resection and TACE for intermediate HCC. We also compare the survival benefits of liver resection in early and intermediate HCC. We find that liver resection can achieve better or at least comparable survival outcomes compared with TACE for intermediate HCC; however, we do not observe a significant difference between liver resection and TACE in terms of safety and morbidity. We conclude that liver resection may improve the short- and long-term survival of carefully selected intermediate HCC patients, and the procedure may be safely performed in the management of intermediate HCC. PMID:27190577

  15. Simultaneously Diagnosed and Successfully Treated Rectovaginal and Vesicovaginal Fistulae after Low Anterior Resection with Concomitant Resection of Female Genitalia

    PubMed Central

    Takagi, Chisato; Baba, Hideo; Yamafuji, Kazuo; Asami, Atsunori; Takeshima, Kaoru; Okamoto, Nobuhiko; Takahashi, Hidena; Kubochi, Kiyoshi

    2017-01-01

    Rectovaginal fistula (RVF) and vesicovaginal fistula (VVF) are infrequent but distressing complications after pelvic surgery. However, their adequate treatment is not well described. Here, we simultaneously encountered and successfully treated RVF and VVF after radical surgery for rectal cancer. A 70-year-old woman underwent low anterior resection (LAR) combined with resection of the uterus, the bilateral adnexa, and the upper side of the vagina, as well as diverted ileostomy for rectal cancer. A month after the surgery, she developed urinary incontinence and underwent medical treatment, but her symptoms did not improve. Evaluation with contrast enema before stoma closure revealed the presence of RVF and VVF. We repaired the VVF and RVF via transabdominal and transperineal approaches. After 6 months, ileostomy was closed and the patient had no recurrence of cancer and fistula. In LAR with hysterectomy and resection of the vaginal wall, there is a risk of RVF and VVF. The excision and closure of the fistula tract and omental flap can be effective to treat both fistulae. PMID:28203133

  16. CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell–like Populations and Diverse Mononuclear Phagocytes

    PubMed Central

    Dee, Christopher T.; Nagaraju, Raghavendar T.; Athanasiadis, Emmanouil I.; Gray, Caroline; Fernandez del Ama, Laura; Johnston, Simon A.; Secombes, Christopher J.

    2016-01-01

    CD4+ T cells are at the nexus of the innate and adaptive arms of the immune system. However, little is known about the evolutionary history of CD4+ T cells, and it is unclear whether their differentiation into specialized subsets is conserved in early vertebrates. In this study, we have created transgenic zebrafish with vibrantly labeled CD4+ cells allowing us to scrutinize the development and specialization of teleost CD4+ leukocytes in vivo. We provide further evidence that CD4+ macrophages have an ancient origin and had already emerged in bony fish. We demonstrate the utility of this zebrafish resource for interrogating the complex behavior of immune cells at cellular resolution by the imaging of intimate contacts between teleost CD4+ T cells and mononuclear phagocytes. Most importantly, we reveal the conserved subspecialization of teleost CD4+ T cells in vivo. We demonstrate that the ancient and specialized tissues of the gills contain a resident population of il-4/13b–expressing Th2-like cells, which do not coexpress il-4/13a. Additionally, we identify a contrasting population of regulatory T cell–like cells resident in the zebrafish gut mucosa, in marked similarity to that found in the intestine of mammals. Finally, we show that, as in mammals, zebrafish CD4+ T cells will infiltrate melanoma tumors and obtain a phenotype consistent with a type 2 immune microenvironment. We anticipate that this unique resource will prove invaluable for future investigation of T cell function in biomedical research, the development of vaccination and health management in aquaculture, and for further research into the evolution of adaptive immunity. PMID:27694495

  17. Tissue-Specific Inactivation of Type 2 Deiodinase Reveals Multilevel Control of Fatty Acid Oxidation by Thyroid Hormone in the Mouse

    PubMed Central

    Fonseca, Tatiana L.; Werneck-De-Castro, Joao Pedro; Castillo, Melany; Bocco, Barbara M.L.C.; Fernandes, Gustavo W.; McAninch, Elizabeth A.; Ignacio, Daniele L.; Moises, Caio C.S.; Ferreira, Alexandre; Gereben, Balázs

    2014-01-01

    Type 2 deiodinase (D2) converts the prohormone thyroxine (T4) to the metabolically active molecule 3,5,3′-triiodothyronine (T3), but its global inactivation unexpectedly lowers the respiratory exchange rate (respiratory quotient [RQ]) and decreases food intake. Here we used FloxD2 mice to generate systemically euthyroid fat-specific (FAT), astrocyte-specific (ASTRO), or skeletal-muscle-specific (SKM) D2 knockout (D2KO) mice that were monitored continuously. The ASTRO-D2KO mice also exhibited lower diurnal RQ and greater contribution of fatty acid oxidation to energy expenditure, but no differences in food intake were observed. In contrast, the FAT-D2KO mouse exhibited sustained (24 h) increase in RQ values, increased food intake, tolerance to glucose, and sensitivity to insulin, all supporting greater contribution of carbohydrate oxidation to energy expenditure. Furthermore, FAT-D2KO animals that were kept on a high-fat diet for 8 weeks gained more body weight and fat, indicating impaired brown adipose tissue (BAT) thermogenesis and/or inability to oxidize the fat excess. Acclimatization of FAT-D2KO mice at thermoneutrality dissipated both features of this phenotype. Muscle D2 does not seem to play a significant metabolic role given that SKM-D2KO animals exhibited no phenotype. The present findings are unique in that they were obtained in systemically euthyroid animals, revealing that brain D2 plays a dominant albeit indirect role in fatty acid oxidation via its sympathetic control of BAT activity. D2-generated T3 in BAT accelerates fatty acid oxidation and protects against diet-induced obesity. PMID:24487027

  18. CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell-like Populations and Diverse Mononuclear Phagocytes.

    PubMed

    Dee, Christopher T; Nagaraju, Raghavendar T; Athanasiadis, Emmanouil I; Gray, Caroline; Fernandez Del Ama, Laura; Johnston, Simon A; Secombes, Christopher J; Cvejic, Ana; Hurlstone, Adam F L

    2016-11-01

    CD4(+) T cells are at the nexus of the innate and adaptive arms of the immune system. However, little is known about the evolutionary history of CD4(+) T cells, and it is unclear whether their differentiation into specialized subsets is conserved in early vertebrates. In this study, we have created transgenic zebrafish with vibrantly labeled CD4(+) cells allowing us to scrutinize the development and specialization of teleost CD4(+) leukocytes in vivo. We provide further evidence that CD4(+) macrophages have an ancient origin and had already emerged in bony fish. We demonstrate the utility of this zebrafish resource for interrogating the complex behavior of immune cells at cellular resolution by the imaging of intimate contacts between teleost CD4(+) T cells and mononuclear phagocytes. Most importantly, we reveal the conserved subspecialization of teleost CD4(+) T cells in vivo. We demonstrate that the ancient and specialized tissues of the gills contain a resident population of il-4/13b-expressing Th2-like cells, which do not coexpress il-4/13a Additionally, we identify a contrasting population of regulatory T cell-like cells resident in the zebrafish gut mucosa, in marked similarity to that found in the intestine of mammals. Finally, we show that, as in mammals, zebrafish CD4(+) T cells will infiltrate melanoma tumors and obtain a phenotype consistent with a type 2 immune microenvironment. We anticipate that this unique resource will prove invaluable for future investigation of T cell function in biomedical research, the development of vaccination and health management in aquaculture, and for further research into the evolution of adaptive immunity.

  19. Aggressive resection of frequent peritoneal recurrences in colorectal cancer contributes to long-term survival

    PubMed Central

    Komori, Koji; Kinoshita, Takashi; Taihei, Oshiro; Ito, Seiji; Abe, Tetsuya; Senda, Yoshiki; Misawa, Kazunari; Ito, Yuich; Uemura, Norihisa; Natsume, Seiji; Kawakami,, Jiro; Ouchi, Akira; Tsutsuyama, Masayuki; Hosoi, Takahiro; Shigeyoshi, Itaru; Akazawa, Tomoyuki; Hayashi, Daisuke; Tanaka, Hideharu; Shimizu, Yasuhiro

    2016-01-01

    ABSTRACT We report a long-term survivor of colorectal cancer who underwent aggressive, frequent resection for peritoneal recurrences. A 58-year-old woman was diagnosed with descending colon cancer. Resection of the descending colon along with lymph node dissection was performed in September 2006. The pathological findings revealed Stage IIA colorectal cancer. The following peritoneal recurrences were removed: two in July 2007, two in the omental fat and two in the pouch of Douglas in June 2008 resected by low anterior resection of the rectum, one in the uterus and right ovarian recurrence resected via bilateral adnexectomy and Hartmann’s procedure in May 2011, and one in the ascending colon by partial resection of the colon wall in December 2011. Postoperative adjuvant chemotherapy (uracil and tegafur/leucovorin, fluorouracil/levofolinate/oxaliplatin/bevacizumab, 5-fluorouracil/leucovorin/bevacizumab, irinotecan/bevacizumab, and irinotecan/panitumumab) was administered. The patient did not desire postoperative adjuvant chemotherapy after the fourth operation. The long-term survival was 6 years and 7 months. PMID:28008206

  20. Pneumocephalus Following Thoracic Surgery with Posterior Chest Wall Resection.

    PubMed

    Müller, Ina; Tönnies, Mario; Pfannschmidt, Joachim; Kaiser, Dirk

    2015-12-01

    Pneumocephalus can be seen after head injury with fracture of the skull-base or in cerebral neoplasm, infection, or after intracranial or spinal surgery. We report on a 69-year-old male patient with pneumocephalus after right-sided lobectomy and en bloc resection of the chest wall for non-small-cell lung cancer. Postoperatively, the patient showed a reduced vigilance level with no response to pain stimuli and anisocoria. The CCT scan revealed an extensive pneumocephalus; following which, the patient underwent neurosurgery with laminectomy and ligature of the transected nerve roots. After operation the patient returned to his baseline mental status.

  1. Clinical Score Predicting Long-Term Survival after Repeat Resection for Recurrent Adrenocortical Carcinoma

    PubMed Central

    Tran, Thuy B; Maithel, Shishir K; Pawlik, Timothy M; Wang, Tracy S; Hatzaras, Ioannis; Phay, John E; Fields, Ryan C; Weber, Sharon M; Sicklick, Jason K; Yopp, Adam C; Duh, Quan-Yang; Solorzano, Carmen C; Votanopoulos, Konstantinos I; Poultsides, George A

    2017-01-01

    BACKGROUND Adrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study was to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC. STUDY DESIGN Patients who underwent curative-intent repeat resection for recurrent ACC at 1 of 13 academic medical centers participating in the US ACC Study Group were identified. End points included morbidity, mortality, and overall survival. RESULTS Fifty-six patients underwent repeat curative-intent resection for recurrent ACC (representing 21% of 265 patients who underwent resection for primary ACC) from 1997 to 2014. Median age was 52 years. Sites of resected recurrence included locoregional only (54%), lung only (14%), liver only (12%), combined locoregional and lung (4%), combined liver and lung (4%), and other distant sites (12%). Thirty-day morbidity and mortality rates were 40% and 5.4%, respectively. Cox regression analysis revealed that the presence of multifocal recurrence, disease-free interval <12 months, and extrapulmonary distant metastases were independent predictors of poor survival. A clinical score consisting of 1-point each for the 3 variables demonstrated good discrimination in predicting survival after repeat resection (5-year: 72% for 0 points, 32% for 1 point, 0% for 2 or 3 points; p = 0.0006, area under the curve = 0.78). CONCLUSIONS Long-term survival after repeat resection for recurrent ACC is feasible when 2 of the following factors are present: solitary tumor, disease-free interval >12 months, and locoregional or pulmonary recurrence. PMID:27618748

  2. Resection after preoperative chemotherapy versus synchronous liver resection of colorectal cancer liver metastases

    PubMed Central

    Kim, Chan W.; Lee, Jong L.; Yoon, Yong S.; Park, In J.; Lim, Seok-Byung; Yu, Chang S.; Kim, Tae W.; Kim, Jin C.

    2017-01-01

    Abstract This study aimed to determine the prognostic effects of preoperative chemotherapy for colorectal cancer liver metastasis (CLM). We retrospectively evaluated 2 groups of patients between January 2006 and August 2012. A total of 53 patients who had ≥3 hepatic metastases underwent resection after preoperative chemotherapy (preoperative chemotherapy group), whereas 96 patients who had ≥3 hepatic metastases underwent resection with a curative intent before chemotherapy for CLM (primary resection group). A propensity score (PS) model was used to compare the both groups. The 3-year disease-free survival (DFS) rates were 31.7% and 20.4% in the preoperative chemotherapy and primary resection groups, respectively (log-rank = 0.015). Analyzing 32 PS matched pairs, we found that the DFS rate was significantly higher in the preoperative chemotherapy group than in the primary resection group (3-year DFS rates were 34.2% and 16.8%, respectively [log-rank = 0.019]). Preoperative chemotherapy group patients had better DFSs than primary resection group patients in various multivariate analyses, including crude, multivariable, average treatment effect with inverse probability of treatment weighting model and PS matching. Responses to chemotherapy are as important as achieving complete resection in cases of multiple hepatic metastases. Preoperative chemotherapy may therefore be preferentially considered for patients who experience difficulty undergoing complete resection for multiple hepatic metastases. PMID:28207557

  3. Dual-row needle arrays under an electromagnetic thermotherapy system for bloodless liver resection surgery.

    PubMed

    Huang, Sheng Chieh; Chang, Yi Yuan; Chao, Ying Jui; Shan, Yan Shen; Lin, Xi Zhang; Lee, Gwo Bin

    2012-03-01

    Electromagnetic thermotherapy has been extensively investigated recently and may become a new surgical modality for a variety of medical applications. It applies a high-frequency alternating magnetic field to heat up magnetic materials inserted within the human body to generate tissue coagulation or cell apoptosis. Using a new procedure with dual-row needle arrays under an electromagnetic thermotherapy system with a feedback temperature control system, this study demonstrates bloodless porcine liver resection, which is challenging using existing methods. In vitro experiments showed that hollowed, stainless-steel needles could be heated up to more than 300 °C within 30 s when centered under the induction coils of the electromagnetic thermotherapy system. In order to generate a wide ablation zone and to prevent the dual-row needle arrays from sticking to the tissue after heating, a constant temperature of 120 °C was applied using a specific treatment protocol. The temperature distribution in the porcine livers was also measured to explore the effective coagulation area. Liver resection was then performed in Lan-Yu pigs. Experimental results showed that seven pigs underwent liver resection without bleeding during surgery and no complications afterward. The dual-row needle arrays combined with the electromagnetic thermotherapy system are thus shown to be promising for bloodless tissue resection.

  4. Correlating Molecular Character of NIR Imaging Agents with Tissue-Specific Uptake

    PubMed Central

    Owens, Eric A.; Hyun, Hoon; Tawney, Joseph G.; Choi, Hak Soo; Henary, Maged

    2015-01-01

    Near-infrared (NIR) fluorescent contrast agents are emerging in optical imaging as sensitive, cost-effective, and nonharmful alternatives to current agents that emit harmful ionizing radiation. Developing spectrally distinct NIR fluorophores to visualize sensitive vital tissues to selectively avoid them during surgical resection of diseased tissue is of great significance. Herein, we report the synthetic variation of pentamethine cyanine fluorophores with modifications of physicochemical properties toward prompting tissue-specific uptake into sensitive tissues (i.e., endocrine glands). Tissue-specific targeting and biodistribution studies revealed localization of contrast agents in the adrenal and pituitary glands, pancreas, and lymph nodes with dependence on molecular characteristics. Incorporation of hydrophobic heterocyclic rings, alkyl groups, and halogens allowed a fine-tuning capability to the hydrophobic character and dipole moment for observing perturbation in biological activity in response to minor structural alterations. These NIR contrast agents have potential for clinical translation for intraoperative imaging in the delineation of delicate glands. PMID:25923454

  5. Tissue specific analysis reveals a differential organization and regulation of both ethylene biosynthesis and E8 during climacteric ripening of tomato

    PubMed Central

    2014-01-01

    Background Solanum lycopersicum or tomato is extensively studied with respect to the ethylene metabolism during climacteric ripening, focusing almost exclusively on fruit pericarp. In this work the ethylene biosynthesis pathway was examined in all major tomato fruit tissues: pericarp, septa, columella, placenta, locular gel and seeds. The tissue specific ethylene production rate was measured throughout fruit development, climacteric ripening and postharvest storage. All ethylene intermediate metabolites (1-aminocyclopropane-1-carboxylic acid (ACC), malonyl-ACC (MACC) and S-adenosyl-L-methionine (SAM)) and enzyme activities (ACC-oxidase (ACO) and ACC-synthase (ACS)) were assessed. Results All tissues showed a similar climacteric pattern in ethylene productions, but with a different amplitude. Profound differences were found between tissue types at the metabolic and enzymatic level. The pericarp tissue produced the highest amount of ethylene, but showed only a low ACC content and limited ACS activity, while the locular gel accumulated a lot of ACC, MACC and SAM and showed only limited ACO and ACS activity. Central tissues (septa, columella and placenta) showed a strong accumulation of ACC and MACC. These differences indicate that the ethylene biosynthesis pathway is organized and regulated in a tissue specific way. The possible role of inter- and intra-tissue transport is discussed to explain these discrepancies. Furthermore, the antagonistic relation between ACO and E8, an ethylene biosynthesis inhibiting protein, was shown to be tissue specific and developmentally regulated. In addition, ethylene inhibition by E8 is not achieved by a direct interaction between ACO and E8, as previously suggested in literature. Conclusions The Ethylene biosynthesis pathway and E8 show a tissue specific and developmental differentiation throughout tomato fruit development and ripening. PMID:24401128

  6. Ischemic Colitis Revealing Polyarteritis Nodosa

    PubMed Central

    Hamzaoui, Amira; Litaiem, Noureddine; Smiti Khanfir, M.; Ayadi, Sofiene; Nfoussi, Haifa; Houman, M. H.

    2013-01-01

    Ischemic colitis is one of the most common intestinal ischemic injuries. It results from impaired perfusion of blood to the bowel and is rarely caused by vasculitis. We report a case of ischemic colitis revealing polyarteritis nodosa (PAN) in a 55-year-old man. Histological examination of the resected colon led to the diagnosis of PAN. PMID:24382967

  7. Murine Ileocolic Bowel Resection with Primary Anastomosis

    PubMed Central

    Perry, Troy; Borowiec, Anna; Dicken, Bryan; Fedorak, Richard; Madsen, Karen

    2014-01-01

    Intestinal resections are frequently required for treatment of diseases involving the gastrointestinal tract, with Crohn’s disease and colon cancer being two common examples. Despite the frequency of these procedures, a significant knowledge gap remains in describing the inherent effects of intestinal resection on host physiology and disease pathophysiology. This article provides detailed instructions for an ileocolic resection with primary end-to-end anastomosis in mice, as well as essential aspects of peri-operative care to maximize post-operative success. When followed closely, this procedure yields a 95% long-term survival rate, no failure to thrive, and minimizes post-operative complications of bowel obstruction and anastomotic leak. The technical challenges of performing the procedure in mice are a barrier to its wide spread use in research. The skills described in this article can be acquired without previous surgical experience. Once mastered, the murine ileocolic resection procedure will provide a reproducible tool for studying the effects of intestinal resection in models of human disease. PMID:25406841

  8. Stress response to laparoscopic liver resection

    PubMed Central

    Ueda, Kazuki; Turner, Patricia

    2004-01-01

    Background: The magnitude of the systemic response is proportional to the degree of surgical trauma. Much has been reported in the literature comparing metabolic and immune responses, analgesia use, or length of hospital stay between laparoscopic and open procedures. In particular, metabolic and immune responses are represented by measuring various chemical mediators as stress responses. Laparoscopic procedures are associated with reduced operative trauma compared with open procedures, resulting in lower systemic response. As a result, laparoscopic procedures are now well accepted for both benign and malignant processes. Laparoscopic liver resection, specifically, is employed for symptomatic and some malignant tumors, following improvements in diagnostic accuracy, laparoscopic devices, and techniques. However, laparoscopic liver resection is still controversial in malignant disease because of complex anatomy, the technical difficulty of the procedure, and questionable indications. There are few reports describing the stress responses associated with laparoscopic liver resection, even though many studies reviewing stress responses have been performed recently in both humans and animal models comparing laparoscopic to conventional open surgery. Although this review examines stress response after laparoscopic liver resection in both an animal and human clinical model, further controlled randomized studies with additional investigations of immunologic parameters are needed to demonstrate the consequences of either minimally invasive surgery or open procedures on perioperative or postoperative stress responses for laparoscopic liver resection. PMID:18333082

  9. Mechanical characterization of the mouse diaphragm with optical coherence elastography reveals fibrosis-related change of direction-dependent muscle tissue stiffness

    NASA Astrophysics Data System (ADS)

    Wang, Shang; Loehr, James A.; Larina, Irina V.; Rodney, George G.; Larin, Kirill V.

    2016-03-01

    The diaphragm, composed of skeletal muscle, plays an important role in respiration through its dynamic contraction. Genetic and molecular studies of the biomechanics of mouse diaphragm can provide great insights into an improved understanding and potential treatment of the disorders that lead to diaphragm dysfunction (i.e. muscular dystrophy). However, due to the small tissue size, mechanical assessment of mouse diaphragm tissue under its proper physiological conditions has been challenging. Here, we present the application of noncontact optical coherence elastography (OCE) for quantitative elastic characterization of ex vivo mouse diaphragm. Phase-sensitive optical coherence tomography was combined with a focused air-puff system to capture and measure the elastic wave propagation from tissue surface. Experiments were performed on wildtype and dystrophic mouse diaphragm tissues containing different levels of fibrosis. The OCE measurements of elastic wave propagation were conducted along both the longitudinal and transverse axis of the muscle fibers. Cross-correlation of the temporal displacement profiles from different spatial locations was utilized to obtain the propagation time delay, which was used to calculate the wave group velocity and to further quantify the tissue Young's modulus. Prior to and after OCE assessment, peak tetanic force was measured to monitor viability of the tissue during the elasticity measurements. Our experimental results indicate a positive correlation between fibrosis level and tissue stiffness, suggesting this elastic-wave-based OCE method could be a useful tool to monitor mechanical properties of skeletal muscle under physiological and pathological conditions.

  10. Silencing tissue inhibitors of metalloproteinases (TIMPs) with short interfering RNA reveals a role for TIMP-1 in hepatic stellate cell proliferation

    SciTech Connect

    Fowell, Andrew J.; Collins, Jane E.; Duncombe, Dale R.; Pickering, Judith A.; Rosenberg, William M.C.; Benyon, R. Christopher

    2011-04-08

    Research highlights: {yields} Myofibroblastic, activated hepatic stellate cells (HSC) play a pivotal role in the development of liver fibrosis. {yields} We used short interfering RNA (siRNA) to investigate the effects of autocrine TIMP-1 and -2 on HSC proliferation. {yields} Specific silencing of TIMP-1, but not TIMP-2, significantly reduces HSC proliferation and is associated with reduced Akt phosphorylation. {yields} TIMP-1 is localised in part to the HSC nucleus. {yields} TIMP-1 might promote liver fibrosis by means other than its previously described anti-apoptotic effect on HSC. -- Abstract: Myofibroblastic, activated hepatic stellate cells (HSC) play a pivotal role in the development of liver fibrosis through the secretion of fibrillar collagens and the tissue inhibitors of metalloproteinase (TIMP)-1 and -2. TIMPs are believed to promote hepatic fibrosis by inhibiting both matrix degradation and apoptosis of HSC. In other cell types, there is evidence that TIMP-1 has effects on proliferation, however the role of TIMPs in the regulation of HSC proliferation remains unexplored. Therefore, we have used short interfering RNA (siRNA) to investigate the effects of autocrine TIMP-1 and -2 on HSC proliferation. TIMP-1 and -2 siRNA were highly effective, producing peak target protein knockdown compared to negative control siRNA of 92% and 63%, respectively. Specific silencing of TIMP-1, using siRNA, significantly reduced HSC proliferation. TIMP-1 was localised in part to the HSC nucleus and TIMP-1 siRNA resulted in loss of both cytoplasmic and nuclear TIMP-1. Attenuated proliferation was associated with reduced Akt phosphorylation and was partially rescued by addition of recombinant TIMP-1. We have revealed a novel autocrine mitogenic effect of TIMP-1 on HSC, which may involve Akt-dependent and specific nuclear mechanisms of action. We suggest that TIMP-1 might promote liver fibrosis by means other than its previously described anti-apoptotic effect on HSC. Moreover

  11. Tissue-based proteomics reveals FXYD3, S100A11 and GSTM3 as novel markers for regional lymph node metastasis in colon cancer.

    PubMed

    Meding, Stephan; Balluff, Benjamin; Elsner, Mareike; Schöne, Cédrik; Rauser, Sandra; Nitsche, Ulrich; Maak, Matthias; Schäfer, Alexander; Hauck, Stefanie M; Ueffing, Marius; Langer, Rupert; Höfler, Heinz; Friess, Helmut; Rosenberg, Robert; Walch, Axel

    2012-12-01

    Regional lymph node metastasis negatively affects prognosis in colon cancer patients. The molecular processes leading to regional lymph node metastasis are only partially understood and proteomic markers for metastasis are still scarce. Therefore, a tissue-based proteomic approach was undertaken for identifying proteins associated with regional lymph node metastasis. Two complementary tissue-based proteomic methods have been employed. MALDI imaging was used for identifying small proteins (≤25 kDa) in situ and label-free quantitative proteomics was used for identifying larger proteins. A tissue cohort comprising primary colon tumours without metastasis (UICC II, pN0, n = 21) and with lymph node metastasis (UICC III, pN2, n = 33) was analysed. Subsequent validation of identified proteins was done by immunohistochemical staining on an independent tissue cohort consisting of primary colon tumour specimens (n = 168). MALDI imaging yielded ten discriminating m/z species, and label-free quantitative proteomics 28 proteins. Two MALDI imaging-derived candidate proteins (FXYD3 and S100A11) and one from the label-free quantitative proteomics (GSTM3) were validated on the independent tissue cohort. All three markers correlated significantly with regional lymph node metastasis: FXYD3 (p = 0.0110), S100A11 (p = 0.0071), and GSTM3 (p = 0.0173). FXYD3 and S100A11 were more highly expressed in UICC II patient tumour tissues. GSTM3 was more highly expressed in UICC III patient tumour tissues. By our tissue-based proteomic approach, we could identify a large panel of proteins which are associated with regional lymph node metastasis and which have not been described so far. Here we show that novel markers for regional lymph metastasis can be identified by MALDI imaging or label-free quantitative proteomics and subsequently validated on an independent tissue cohort.

  12. Endoscopic Resection of the Tarsal Tunnel Ganglion.

    PubMed

    Lui, Tun Hing

    2016-10-01

    The tarsal tunnel ganglion is a cause of posterior tarsal tunnel syndrome. Open resection of the ganglion calls for release of the flexor retinaculum and dissection around the tibial neurovascular bundle. This can induce fibrosis around the tibial nerve. We report the technique of endoscopic resection of the tarsal tunnel ganglion. It is indicated for tarsal tunnel ganglia arising from the adjacent joints or tendon sheaths and compressing the tibial nerve from its deep side. It is contraindicated if there is other pathology of the tarsal tunnel that demands open surgery; if the ganglion compresses the tibial nerve from its superficial side, which calls for a different endoscopic approach using the ganglion portal; or if an intraneural ganglion of the tibial nerve is present. The purpose of this technical note is to describe a minimally invasive approach for endoscopic resection of the tarsal tunnel ganglion.

  13. The difficulty of laparoscopic liver resection.

    PubMed

    Ban, Daisuke; Kudo, Atsushi; Ito, Hiromitsu; Mitsunori, Yusuke; Matsumura, Satoshi; Aihara, Arihiro; Ochiai, Takanori; Tanaka, Shinji; Tanabe, Minoru; Itano, Osamu; Kaneko, Hironori; Wakabayashi, Go

    2015-06-01

    Grading of difficulty is needed for laparoscopic liver resection (LLR). Indications for LLR are expanding worldwide from minor to major resections, particularly in institutions having surgeons with advanced skills. If the degrees of surgical difficulty were defined, it would serve as a useful guide when introducing LLR and stepping up to the more advanced LLR. As no previous study has addressed the degrees of difficulty of various LLR procedures, we devised a practical scoring system for this purpose. We extracted the following five factors from preoperative information to score difficulty levels: (1) tumor location, (2) extent of liver resection, (3) tumor size, (4) proximity to major vessels, and (5) liver function. This difficulty index is comprised of the cumulative score for the five individual factors. There has not yet been a standard definition of difficulty. Our proposed scoring system might be a practical means of assessing the difficulty of LLR procedures. However, this system must be prospectively validated.

  14. Reduction of Pulmonary Function After Surgical Lung Resections of Different Volume

    PubMed Central

    Cukic, Vesna

    2014-01-01

    Introduction: In recent years an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused with common etiologic factor - smoking cigarettes. Objective: To determine how big the loss of lung function is after surgical resection of lung of different range. Methods: The study was done on 58 patients operated at the Clinic for thoracic surgery KCU Sarajevo, previously treated at the Clinic for pulmonary diseases “Podhrastovi” in the period from 01.06.2012. to 01.06.2014. The following resections were done: pulmectomy (left, right), lobectomy (upper, lower: left and right). The values of postoperative pulmonary function were compared with preoperative ones. As a parameter of lung function we used FEV1 (forced expiratory volume in one second), and changes in FEV1 are expressed in liters and in percentage of the recorded preoperative and normal values of FEV1. Measurements of lung function were performed seven days before and 2 months after surgery. Results: Postoperative FEV1 was decreased compared to preoperative values. After pulmectomy the maximum reduction of FEV1 was 44%, and after lobectomy it was 22% of the preoperative values. Conclusion: Patients with airway obstruction are limited in their daily life before the surgery, and an additional loss of lung tissue after resection contributes to their inability. Potential benefits of lung resection surgery should be balanced in relation to postoperative morbidity and mortality. PMID:25568542

  15. Intraoperative Near-Infrared Imaging of Surgical Wounds after Tumor Resections Can Detect Residual Disease

    PubMed Central

    Madajewski, Brian; Judy, Brendan F.; Mouchli, Anas; Kapoor, Veena; Holt, David; Wang, May D.; Nie, Shuming; Singhal, Sunil

    2012-01-01

    Background Surgical resection remains the most effective therapy for solid tumors worldwide. The most important prognostic indicator for cure following cancer surgery is a complete resection with no residual disease. However, intraoperative detection of retained cancer cells after surgery is challenging, and residual disease continues to be the most common cause of local failure. We hypothesized visual enhancement of tumors using near-infrared imaging could potentially identify tumor deposits in the wound after resection. Methods A small animal model of surgery and retained disease was developed. Residual tumor deposits in the wound were targeted using an FDA approved imaging agent, indocyanine green, by the enhanced permeability and retention (EPR) effect. A novel hand-held spectrometer was used to optically visualize retained disease after surgery. Results We found residual disease using near-infrared imaging during surgery that was not visible to the naked eye or microCT. Furthermore, examination of tumor nodules was remarkably precise in delineating margins from normal surrounding tissues. This approach was most successful for tumors with increased neovasculature. Conclusions The results suggest that near-infrared examination of the surgical wound after curative resection can potentially enable the surgeon to locate residual disease. The data in this study is the basis of an ongoing Phase I/II clinical trial in patients who undergo resection for lung and breast cancer. PMID:22932668

  16. Concurrent Chemoradiotherapy in Resected Extrahepatic Cholangiocarcinoma

    SciTech Connect

    Nelson, John W.; Ghafoori, A. Paiman; Willett, Christopher G.; Tyler, Douglas S.; Pappas, Theodore N.; Clary, Bryan M.; Hurwitz, Herbert I.; Bendell, Johanna C.; Morse, Michael A.; Clough, Robert W.; Czito, Brian G.

    2009-01-01

    Purpose: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy. Methods and Materials: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors. Results: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treated neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age {<=}60 years and perineural involvement adversely affected survival on univariate analysis. Patients undergoing R0 resection had a significantly improved rate of local control but no survival advantage. Despite having more advanced disease at presentation, patients treated neoadjuvantly had a longer survival (5-year survival 53% vs. 23%, p = 0.16) and similar rates of Grade 2-3 surgical morbidity (16% vs. 33%, p = 0.24) compared with those treated in the postoperative setting. Conclusion: These study results suggest a possible local control benefit from chemoradiotherapy combined with surgery in patients with advanced, resected biliary cancer. Furthermore, our results suggest that a treatment strategy that includes preoperative chemoradiotherapy might result in improved tumor resectability with similar surgical morbidity compared with patients treated postoperatively, as well as potentially improved survival outcomes. Distant failure remains a significant failure pattern, suggesting the need for more effective systemic

  17. Abdominosacral resection for locally recurring rectal cancer

    PubMed Central

    Belli, Filiberto; Gronchi, Alessandro; Corbellini, Carlo; Milione, Massimo; Leo, Ermanno

    2016-01-01

    AIM To investigate feasibility and outcome of abdominal-sacral resection for treatment of locally recurrent rectal adenocarcinoma. METHODS A population of patients who underwent an abdominal-sacral resection for posterior recurrent adenocarcinoma of the rectum at the National Cancer Institute of Milano, between 2005 and 2013, is considered. Retrospectively collected data includes patient characteristics, treatment and pathology details regarding the primary and the recurrent rectal tumor surgical resection. A clinical and instrumental follow-up was performed. Surgical and oncological outcome were investigated. Furthermore an analytical review of literature was conducted in order to compare our case series with other reported experiences. RESULTS At the time of abdomino-sacral resection, the mean age of patients was 55 (range, 38-64). The median operating time was 380 min (range, 270-480). Sacral resection was performed at S2/S3 level in 3 patients, S3/S4 in 3 patients and S4/S5 in 4 patients. The median operating time was 380 ± 58 min. Mean intraoperative blood loss was 1750 mL (range, 200-680). The median hospital stay was 22 d. Overall morbidity was 80%, mainly type II complication according to the Clavien-Dindo classification. Microscopically negative margins (R0) is obtained in all patients. Overall 5-year survival after first surgical procedure is 60%, with a median survival from the first surgery of 88 ± 56 mo. The most common site of re-recurrence was intrapelvic. CONCLUSION Sacral resection represents a feasible approach to posterior rectal cancer recurrence without evidence of distant spreading. An accurate staging is essential for planning the best therapy. PMID:28070232

  18. Non-destructive phase contrast hard x-ray imaging to reveal the three-dimensional microstructure of soft and hard tissues

    NASA Astrophysics Data System (ADS)

    Khimchenko, Anna; Schulz, Georg; Deyhle, Hans; Hieber, Simone E.; Hasan, Samiul; Bikis, Christos; Schulz, Joachim; Costeur, Loïc.; Müller, Bert

    2016-04-01

    X-ray imaging in the absorption contrast mode is an established method of visualising calcified tissues such as bone and teeth. Physically soft tissues such as brain or muscle are often imaged using magnetic resonance imaging (MRI). However, the spatial resolution of MRI is insufficient for identifying individual biological cells within three-dimensional tissue. X-ray grating interferometry (XGI) has advantages for the investigation of soft tissues or the simultaneous three-dimensional visualisation of soft and hard tissues. Since laboratory microtomography (μCT) systems have better accessibility than tomography set-ups at synchrotron radiation facilities, a great deal of effort has been invested in optimising XGI set-ups for conventional μCT systems. In this conference proceeding, we present how a two-grating interferometer is incorporated into a commercially available nanotom m (GE Sensing and Inspection Technologies GmbH) μCT system to extend its capabilities toward phase contrast. We intend to demonstrate superior contrast in spiders (Hogna radiata (Fam. Lycosidae) and Xysticus erraticus (Fam. Thomisidae)), as well as the simultaneous visualisation of hard and soft tissues. XGI is an imaging modality that provides quantitative data, and visualisation is an important part of biomimetics; consequently, hard X-ray imaging provides a sound basis for bioinspiration, bioreplication and biomimetics and allows for the quantitative comparison of biofabricated products with their natural counterparts.

  19. Phylogenic diversity and tissue specificity of fungal endophytes associated with the pharmaceutical plant, Stellera chamaejasme L. revealed by a cultivation-independent approach.

    PubMed

    Jin, Hui; Yang, Xiaoyan; Lu, Dengxue; Li, Chunjie; Yan, Zhiqiang; Li, Xiuzhuang; Zeng, Liming; Qin, Bo

    2015-10-01

    The fungal endophytes associated with medicinal plants have been demonstrated as a reservoir with novel natural products useful in medicine and agriculture. It is desirable to explore the species composition, diversity and tissue specificity of endophytic fungi that inhabit in different tissues of medicinal plants. In this study, a culture-independent survey of fungal diversity in the rhizosphere, leaves, stems and roots of a toxic medicinal plant, Stellera chamaejasme L., was conducted by sequence analysis of clone libraries of the partial internal transcribed spacer region. Altogether, 145 fungal OTUs (operational taxonomic units), represented by 464 sequences, were found in four samples, of these 109 OTUs (75.2 %) belonging to Ascomycota, 20 (13.8 %) to Basidiomycota, 14 (9.7 %) to Zygomycota, 1 (0.7 %) to Chytridiomycota, and 1 (0.7 %) to Glomeromycota. The richness and diversity of fungal communities were strongly influenced by plant tissue environments, and the roots are associated with a surprisingly rich endophyte community. The endophyte assemblages associated with S. chamaejasme were strongly shaped by plant tissue environments, and exhibited a certain degree of tissue specificity. Our results suggested that a wide variety of fungal assemblages inhabit in S. chamaejasme, and plant tissue environments conspicuously influence endophyte community structure.

  20. Laparoscope resection of retroperitoneal ectopic insulinoma: A rare case

    PubMed Central

    Liu, Jie; Zhang, Cheng-Wu; Hong, De-Fei; Wu, Jia; Yang, Hong-Guo; Chen, Yuan; Zhao, Da-Jian; Zhang, Yu-Hua

    2015-01-01

    Ectopic insulinoma is a very rare and dormant tumor. Here we report the case of a 79-year-old female who presented with repeated episodes of hypoglycemia and was diagnosed with insulinoma based on laboratory and imaging examinations. Computed tomography and positron emission tomography revealed a tumor in the retroperitoneum under and left of the hepatoduodenal ligament, which was resected successfully using a laparoscopic approach. Pathologic results revealed an ectopic insulinoma, which was confirmed immunohistochemically. Ectopic insulinomas are accompanied by hypoglycemia that can be misdiagnosed as drug- or disease-induced. These tumors are difficult to diagnose and locate, particularly in atypical cases or for very small tumors. Synthetic or targeted examinations, including low blood glucose, elevated insulin, proinsulin, and C-peptide levels, 48-h fasting tests, and relevant imaging methods should be considered for suspected cases of insulinoma. Surgery is the treatment of choice for patients with insulinoma, and laparoscopic resection is a feasible and effective method for select ectopic insulinoma cases. PMID:25892896

  1. Imaging of Resected Nonfunctioning Pituitary Adenomas: The Cost of Surveillance

    PubMed Central

    Kistka, Heather M.; Kasl, Rebecca A.; Nayeri, Arash; Utz, Andrea L.; Weaver, Kyle D.; Chambless, Lola B.

    2015-01-01

    Objectives To determine the cost of annual magnetic resonance imaging (MRI) surveillance after resection of nonfunctioning pituitary adenomas (NFPAs) and its effectiveness in reducing visual compromise due to tumor recurrence. Design Retrospective case series. Setting Vanderbilt University Medical Center (2003–2011). Participants A total of 120 patients underwent primary transsphenoidal resection and surveillance of NFPAs between 2003 and 2011. Main Outcome Measures Time from initial surgery to most recent imaging or progression. Surveillance MRI costs according to Centers for Medicare and Medicaid database and visual field deficits. Results Patients received 382 surveillance scans at a total cost of $218,477.30. The median follow-up was 47 months (interquartile range [IQR]: 26–76), and the median interval between scans was 357 days (IQR: 225–434). Overall, 50 scans (13%) revealed tumor growth. The cost per scan revealing growth was $4,369.55. The cost to identify 19 patients (16%) with clinically significant growth was $11,498.80 per patient. A total of 5 of 19 patients (26%) experienced new visual deficits prior to intervention. Patients with visual decline tended to have longer scan intervals than those with preserved vision (mean: 239 versus 794 days; p = 0.0584). No patient with annual surveillance imaging experienced visual decline. Conclusions Annual MRI scans are a sensitive and cost-conscious method to identify NFPA recurrence prior to visual decline. PMID:26401475

  2. Right Thoracoabdominal Approach for Retrocardiac Paraganglioma Resection

    PubMed Central

    Laparra-Escareno, Hugo; Anaya-Ayala, Javier E.; Lizola, Rene; Torres-Machorro, Adriana; Gamboa-Domínguez, Armando

    2017-01-01

    Paragangliomas are rare extra-adrenal tumors of sympathetic or parasympathetic paraganglia origin; of these, mediastinal paragangliomas are 2% of all cases. We present the case of a 21-year-old woman with uncontrolled arterial hypertension who had a functioning 6.5 × 6.2-cm retrocardiac paraganglioma firmly attached to the pericardium. The patient underwent tumor resection via a right thoracoabdominal incision; this surgical approach enabled adequate exposure for complete resection without institution of cardiopulmonary bypass or need for cardiac reconstruction or autotransplantation. Ten months postoperatively, the patient was doing well and was no longer hypertensive. PMID:28265216

  3. Resection of a plantar calcaneal spur using the holmium:yttrium-aluminum-garnet (Ho:YAG) laser.

    PubMed

    Smith, W K; Noriega, J A; Smith, W K

    2001-03-01

    Many procedures have been described for the resection of plantar calcaneal spurs as treatment of heel spur syndrome and chronic plantar fasciitis. Most of these techniques involve a medial incision of between 2 and 6 cm for adequate exposure of the calcaneal spur. This article describes a new technique for resecting a calcaneal spur with a smaller medial incision using the holmium:yttrium-aluminum-garnet (Ho:YAG) laser. This laser permits adequate resection of a plantar calcaneal spur as well as coagulation of the bone and surrounding tissues. This minimally invasive procedure has been used with good results over the past year by the senior author (W.K.S.) for the resection of calcaneal spurs.

  4. [Assessment of anaesthesia sufficiency and stress response during liver resections].

    PubMed

    Shiganova, A M; Vyzhigina, M A; Buniatian, K A; Vinnitskiĭ, L I; Samokhina, L O; Golovkin, A S; Balaian, O V; Iur'eva, L A

    2013-01-01

    Recently number of patients undergoing a surgery for primary and secondary liver damages is increased. Thus an adequate and safe anaesthesiological care for the surgeries is a very actual problem. The article deals with a study of anaesthesiological care in 51 patients. 26 patients (51%) received multimodal balanced anaesthesia based on sevoflurane and 25 patients (49%) received multimodal balanced anaesthesia based on continuous propofol infusion. Monitoring of haemodynamics, acid-base balance, common liquid volume, intracellular and extracellular liquid, stress hormones (cortisol and prolactin) was carried out during the surgeries. Haemodynamics and infusion and transfusion therapy were adequate during both methods of anaesthesiological care for liver resections. Strongly marked tissue injury during surgery causes neuroendocrine stress. Cortisol activity during anaesthesia based on continuous propofol infusion was less than during anaesthesia based on sevoflurane. This fact shows that propofol provides stronger protection than sevoflurane. Adequate level of anaesthesia does not cause outoregulative mechanisms suppression which is important during strongly traumatic surgery. Anaesthesia based on sevoflurane both to anaesthesia based on continuous propofol infusion is a method of choice for liver resection.

  5. Liver resection in children, using a water-jet.

    PubMed

    Hata, Y; Sasaki, F; Takahashi, H; Ohkawa, Y; Taguchi, K; Une, Y; Uchino, J

    1994-05-01

    The water-jet method has been used during hepatic resection in children. The instrument cuts the hepatic tissue by means of a high-pressure fine water-jet, while the exposed intrahepatic vessels are spared injury. Physiological saline was used for the jet water, and pressure of 12 to 15 kilograms of force per square centimeter (kgf/cm2) through a 0.15-mm-diameter nozzle was found to be optimal for cutting the liver parenchyma. The authors evaluated the usefulness of the water-jet dissector (n = 8) during bisegmentectomy or trisegmentectomy in comparison to the Cavitron Ultrasonic Surgical Aspirator (CUSA) (n = 5). The mean operation time was 4.08 +/- 0.87 hours for the water-jet group and 5.08 +/- 1.33 hours for the CUSA group. The mean blood loss was 602 +/- 659 mL for the water-jet group and 1,036 +/- 521 mL for the CUSA group. Although there were no significant differences with respect to operation time, blood loss, or postoperative complications, the liver parenchyma was dissected more easily using the water-jet. The authors believe that the mechanical simplicity and safety of the water-jet method will lead to its more widespread use in liver resection in children.

  6. A projective surgical navigation system for cancer resection

    NASA Astrophysics Data System (ADS)

    Gan, Qi; Shao, Pengfei; Wang, Dong; Ye, Jian; Zhang, Zeshu; Wang, Xinrui; Xu, Ronald

    2016-03-01

    Near infrared (NIR) fluorescence imaging technique can provide precise and real-time information about tumor location during a cancer resection surgery. However, many intraoperative fluorescence imaging systems are based on wearable devices or stand-alone displays, leading to distraction of the surgeons and suboptimal outcome. To overcome these limitations, we design a projective fluorescence imaging system for surgical navigation. The system consists of a LED excitation light source, a monochromatic CCD camera, a host computer, a mini projector and a CMOS camera. A software program is written by C++ to call OpenCV functions for calibrating and correcting fluorescence images captured by the CCD camera upon excitation illumination of the LED source. The images are projected back to the surgical field by the mini projector. Imaging performance of this projective navigation system is characterized in a tumor simulating phantom. Image-guided surgical resection is demonstrated in an ex-vivo chicken tissue model. In all the experiments, the projected images by the projector match well with the locations of fluorescence emission. Our experimental results indicate that the proposed projective navigation system can be a powerful tool for pre-operative surgical planning, intraoperative surgical guidance, and postoperative assessment of surgical outcome. We have integrated the optoelectronic elements into a compact and miniaturized system in preparation for further clinical validation.

  7. Application of SLT contact laser in resection of brain tumors

    NASA Astrophysics Data System (ADS)

    Li, Han-Jie; Li, Zhi-Qiang; Li, Chan-Yuan

    1998-11-01

    28 cases of brain tumors were operated by SLT contact Nd:YAG laser from October 1995 to May 1997 in our hospital. Among these, 14 are menin-giomas, 5 are astrocytomas. Others are tumors such as acoustic neuromas, craniopharyngiomas, etc 21 cases underwent common craniotomy, 3, laser endoscopy operation; and 4, laser therapy under microscopy. Method of tumor resection: firstly, cutting and separating the tumor from brain tissues with GRP by 5-15w; secondly, vaporizing parenchyma of tumor with MTRL and sucking it, again, cutting and separating and so on, lastly removing the tumor entirely. The power of vaporization for glioma or tumors in ventricles is about 20-30w, but for meningiomas, 30-60w. MT was used on power of 15-20w to coagulate and homeostate the left cavity of tumor. According to our experience, laser operation can make bleeding reduced markedly, tumor resection become more thorough, and postoperative response and complications decrease obviously.

  8. Spatiotemporal complexity of ventricular fibrillation revealed by tissue mass reduction in isolated swine right ventricle. Further evidence for the quasiperiodic route to chaos hypothesis.

    PubMed Central

    Kim, Y H; Garfinkel, A; Ikeda, T; Wu, T J; Athill, C A; Weiss, J N; Karagueuzian, H S; Chen, P S

    1997-01-01

    We have presented evidence that ventricular fibrillation is deterministic chaos arising from quasiperiodicity. The purpose of this study was to determine whether the transition from chaos (ventricular fibrillation, VF) to periodicity (ventricular tachycardia) through quasiperiodicity could be produced by the progressive reduction of tissue mass. In isolated and perfused swine right ventricular free wall, recording of single cell transmembrane potentials and simultaneous mapping (477 bipolar electrodes, 1.6 mm resolution) were performed. The tissue mass was then progressively reduced by sequential cutting. All isolated tissues fibrillated spontaneously. The critical mass to sustain VF was 19.9 +/- 4.2 g. As tissue mass was decreased, the number of wave fronts decreased, the life-span of reentrant wave fronts increased, and the cycle length, the diastolic interval, and the duration of action potential lengthened. There was a parallel decrease in the dynamical complexity of VF as measured by Kolmogorov entropy and Poincaré plots. A period of quasiperiodicity became more evident before the conversion from VF (chaos) to a more regular arrhythmia (periodicity). In conclusion, a decrease in the number of wave fronts in ventricular fibrillation by tissue mass reduction causes a transition from chaotic to periodic dynamics via the quasiperiodic route. PMID:9366563

  9. Analyzing gene expression from whole tissue vs. different cell types reveals the central role of neurons in predicting severity of Alzheimer's disease.

    PubMed

    Stempler, Shiri; Ruppin, Eytan

    2012-01-01

    Alterations in gene expression resulting from Alzheimer's disease have received considerable attention in recent years. Although expression has been investigated separately in whole brain tissue, in astrocytes and in neurons, a rigorous comparative study quantifying the relative utility of these sources in predicting the progression of Alzheimer's disease has been lacking. Here we analyze gene expression from neurons, astrocytes and whole tissues across different brain regions, and compare their ability to predict Alzheimer's disease progression by building pertaining classification models based on gene expression sets annotated to different biological processes. Remarkably, we find that predictions based on neuronal gene expression are significantly more accurate than those based on astrocyte or whole tissue expression. The findings explicate the central role of neurons, particularly as compared to glial cells, in the pathogenesis of Alzheimer's disease, and emphasize the importance of measuring gene expression in the most relevant (pathogenically 'proximal') single cell types.

  10. Are Histological Findings of Thulium Laser Vapo-Enucleation Versus Transurethral Resection of the Prostate Comparable?

    PubMed

    Carmignani, Luca; Macchi, Alberto; Ratti, Dario; Finkelberg, Elisabetta; Casellato, Stefano; Bozzini, Giorgio; Maruccia, Serena; Marenghi, Carlo; Picozzi, Stefano

    2015-09-01

    We investigated if an adequate histological diagnosis can be made from tissue after Thulium laser vapo-enucleation of the prostate (ThuVEP) and whether it is comparable to transurethral prostate resection (TURP) tissue findings in patients with symptomatic benign prostatic hyperplasia. We analyzed 350 ThuLEP and 100 matched TURP tissue specimens from patients who underwent one of the two procedures between January 2009 and June 2014. Thulium Laser Enucleation of Prostate (ThuVEP) was combined with mechanical morcellation of the resected lobe. Each histological specimen was reviewed by two pathologists. Preoperative prostate ultrasound volume, total serum prostatic specific antigen and postoperative tissue weight were evaluated. Microscopic histological diagnosis was assessed by standard histological techniques and immunohistochemical evaluation. Patients were comparable in terms of age and preoperative total serum prostate specific antigen. Incidental adenocarcinoma and high grade PIN of the prostate were diagnosed in a comparable percent of specimens in the 2 groups (2.5 % in the ThuVEP group versus 3 % in the TURP group). Tissue thermal artifacts induced by the Thulium laser are mostly due to coagulation as that of the conventional monopolar diathermy in TURP. Tissue quality was maintained in the ThuVEP histological specimens. Tissue maintain histological characteristics and proprieties without modification for successive immunoistochemical analysis. The pathologist ability to detect incidental prostate cancer and PIN was maintained even if there is a quoted of vaporized tissue.

  11. An extensive allelic series of Drosophila kae1 mutants reveals diverse and tissue-specific requirements for t6A biogenesis

    PubMed Central

    Lin, Ching-Jung; Smibert, Peter; Zhao, Xiaoyu; Hu, Jennifer F.; Ramroop, Johnny; Kellner, Stefanie M.; Benton, Matthew A.; Govind, Shubha; Dedon, Peter C.; Sternglanz, Rolf; Lai, Eric C.

    2015-01-01

    N6-threonylcarbamoyl-adenosine (t6A) is one of the few RNA modifications that is universally present in life. This modification occurs at high frequency at position 37 of most tRNAs that decode ANN codons, and stabilizes cognate anticodon–codon interactions. Nearly all genetic studies of the t6A pathway have focused on single-celled organisms. In this study, we report the isolation of an extensive allelic series in the Drosophila ortholog of the core t6A biosynthesis factor Kae1. kae1 hemizygous larvae exhibit decreases in t6A that correlate with allele strength; however, we still detect substantial t6A-modified tRNAs even during the extended larval phase of null alleles. Nevertheless, complementation of Drosophila Kae1 and other t6A factors in corresponding yeast null mutants demonstrates that these metazoan genes execute t6A synthesis. Turning to the biological consequences of t6A loss, we characterize prominent kae1 melanotic masses and show that they are associated with lymph gland overgrowth and ectopic generation of lamellocytes. On the other hand, kae1 mutants exhibit other phenotypes that reflect insufficient tissue growth. Interestingly, whole-tissue and clonal analyses show that strongly mitotic tissues such as imaginal discs are exquisitely sensitive to loss of kae1, whereas nonproliferating tissues are less affected. Indeed, despite overt requirements of t6A for growth of many tissues, certain strong kae1 alleles achieve and sustain enlarged body size during their extended larval phase. Our studies highlight tissue-specific requirements of the t6A pathway in a metazoan context and provide insights into the diverse biological roles of this fundamental RNA modification during animal development and disease. PMID:26516084

  12. Arthroscopically assisted central physeal bar resection.

    PubMed

    Marsh, James S; Polzhofer, Gert K

    2006-01-01

    Thirty-seven central physeal bars were removed with an arthroscopically assisted technique. Thirty children (32 cases) have been followed to maturity or physeal closure. There were 19 boys and 11 girls, aged 4-14 years (mean, 9.5 years). Site of arrest was distal femur (15), proximal tibia (9), distal tibia (6), and distal radius (2). Mean follow-up was 6.5 years (range, 2-12 years). Adequate longitudinal growth was realized in 21 patients (70%) just after bar resection. Five patients (17%) required osteotomy, lengthening, or epiphysiodesis in addition to bar resection. In 4 patients (13%), bar resection failed. Failures occurred in those patients whose source of growth arrest was infection (3) or degree of physeal trauma approached 50% (1 case). This is the first series that studies and documents the efficacy of the arthroscope in central physeal bar resection. It provides the best visualization with minimal morbidity. The technique is described, including a discussion of technical tips and pitfalls.

  13. Laparoscopic resection of retroperitoneal benign neurilemmoma

    PubMed Central

    Park, Joon Seong; Kang, Chang Moo; Yoon, Dong Sup; Lee, Woo Jung

    2017-01-01

    Purpose The aim of this study was to verify that laparoscopic resection for treating retroperitoneal benign neurilemmoma (NL) is expected to be favorable for complete resection of tumor with technical feasibility and safety. Methods We retrospectively analyzed 47 operations for retroperitoneal neurogenic tumor at Yonsei University College of Medicine, Severance Hospital and Gangnam Severance Hospital between January 2005 and September 2015. After excluding 21 patients, the remaining 26 were divided into 2 groups: those who underwent open surgery (OS) and those who underwent laparoscopic surgery (LS). We compared clinicopathological features between the 2 groups. Results There was no significant difference in operation time, estimated blood loss, transfusion, complication, recurrence, or follow-up period between 2 groups. Postoperative hospital stay was significantly shorter in the LS group versus the OS group (OS vs. LS, 7.00 ± 3.43 days vs. 4.50 ± 2.16 days; P = 0.031). Conclusion We suggest that laparoscopic resection of retroperitoneal benign NL is feasible and safe by obtaining complete resection of the tumor. LS for treating retroperitoneal benign NL could be useful with appropriate laparoscopic technique and proper patient selection. PMID:28289669

  14. Resection planning for robotic acoustic neuroma surgery

    NASA Astrophysics Data System (ADS)

    McBrayer, Kepra L.; Wanna, George B.; Dawant, Benoit M.; Balachandran, Ramya; Labadie, Robert F.; Noble, Jack H.

    2016-03-01

    Acoustic neuroma surgery is a procedure in which a benign mass is removed from the Internal Auditory Canal (IAC). Currently this surgical procedure requires manual drilling of the temporal bone followed by exposure and removal of the acoustic neuroma. This procedure is physically and mentally taxing to the surgeon. Our group is working to develop an Acoustic Neuroma Surgery Robot (ANSR) to perform the initial drilling procedure. Planning the ANSR's drilling region using pre-operative CT requires expertise and around 35 minutes' time. We propose an approach for automatically producing a resection plan for the ANSR that would avoid damage to sensitive ear structures and require minimal editing by the surgeon. We first compute an atlas-based segmentation of the mastoid section of the temporal bone, refine it based on the position of anatomical landmarks, and apply a safety margin to the result to produce the automatic resection plan. In experiments with CTs from 9 subjects, our automated process resulted in a resection plan that was verified to be safe in every case. Approximately 2 minutes were required in each case for the surgeon to verify and edit the plan to permit functional access to the IAC. We measured a mean Dice coefficient of 0.99 and surface error of 0.08 mm between the final and automatically proposed plans. These preliminary results indicate that our approach is a viable method for resection planning for the ANSR and drastically reduces the surgeon's planning effort.

  15. Polyp Resection - Controversial Practices and Unanswered Questions.

    PubMed

    von Renteln, Daniel; Pohl, Heiko

    2017-03-09

    Detection and complete removal of precancerous neoplastic polyps are central to effective colorectal cancer screening. The prevalence of neoplastic polyps in the screening population in the United States is likely >50%. However, most persons with neoplastic polyps are never destined to develop cancer, and do not benefit for finding and removing polyps, and may only be harmed by the procedure. Further 70-80% of polyps are diminutive (≤5 mm) and such polyps almost never contain cancer. Given the questionable benefit, the high-cost and the potential risk changing our approach to the management of diminutive polyps is currently debated. Deemphasizing diminutive polyps and shifting our efforts to detection and complete removal of larger and higher-risk polyps deserves discussion and study. This article explores three controversies, and emerging concepts related to endoscopic polyp resection. First, we discuss challenges of optical resect-and-discard strategy and possible alternatives. Second, we review recent studies that support the use of cold snare resection for ≥5 mm polyps. Thirdly, we examine current evidence for prophylactic clipping after resection of large polyps.

  16. Intraorbital meningioma: resection through modified orbitozygomatic craniotomy.

    PubMed

    Cohen-Gadol, Aaron A

    2012-01-01

    Intraorbital meningiomas are challenging lesions to excise because of their location and the restricted surgical corridor available due to the presence of important neighboring structures. Lesions located in the posterior one-third of the orbit require skull base approaches for their exposure and safe resection. Frontoorbital and modified orbitozygomatic (OZ) craniotomies may facilitate the exposure and resection of masses in the posterior intraorbital space. Specifically, the one-piece modified OZ craniotomy provides many advantages of the "full" OZ craniotomy (which includes a more extensive zygomatic osteotomy). The modified OZ approach minimizes the extent of frontal lobe retraction and provides ample amount of space for the surgeon to exploit all the working angles to resect the tumor. The following video presentation discusses the nuances of technique for resection of an intraorbital meningioma through modified OZ approach and optic nerve decompression. The nuances of technique will be discussed. The video can be found here: http://youtu.be/fP5X2QNr5qk.

  17. E-cadherin's role in development, tissue homeostasis and disease: Insights from mouse models: Tissue-specific inactivation of the adhesion protein E-cadherin in mice reveals its functions in health and disease.

    PubMed

    Schneider, Marlon R; Kolligs, Frank T

    2015-03-01

    Recent studies uncovered critical roles of the adhesion protein E-cadherin in health and disease. Global inactivation of Cdh1, the gene encoding E-cadherin in mice, results in early embryonic lethality due to an inability to form the trophectodermal epithelium. To unravel E-cadherin's functions beyond development, numerous mouse lines with tissue-specific disruption of Cdh1 have been generated. The consequences of E-cadherin loss showed great variability depending on the tissue in question, ranging from nearly undetectable changes to a complete loss of tissue structure and function. This review focuses on these studies and discusses how they provided important insights into E-cadherin's role in cell adhesion, proliferation and differentiation, and its consequences for biological processes as epithelial-to-mesenchymal transition, vascularization, and carcinogenesis. Lastly, we present some perspectives and possible approaches for future research.

  18. Cyanoacrylate adhesive with conjunctival resection and superficial keratectomy in Mooren's ulcer.

    PubMed

    Agrawal, V; Kumar, A; Sangwan, V; Rao, G N

    1996-03-01

    Seventeen eyes of thirteen patients with Mooren's ulcer were treated with a combination therapy of local and systemic steroids, conjunctival resection, superficial keratectomy and application of cyanoacrylate tissue adhesive. The pathology was classified as acute, subacute and chronic. Ulcers were graded based on the extent of corneal thinning, degree and extent of ulceration, and amount of inflammation. Fourteen eyes (82.4%) healed completely with formation of a vascularised scars, while three eyes (17.6%) failed to respond to treatment and either went into phthisis bulbi or healed with gross tissue distortion. Our study suggests an early intervention of this therapy with cyanoacrylate tissue adhesive application for effective control of Mooren's ulceration.

  19. Histomorphological features of resected bladder tumors: Do energy source makes any difference

    PubMed Central

    Saini, Ashish Kumar; Ahuja, Arvind; Seth, Amlesh; Dogra, Prem Nath; Kumar, Rajeev; Singh, Prabhjot; Gupta, Siddhartha Dutta

    2015-01-01

    Context: The recent advent of bipolar energy in bladder tumor resection has raised many questions regarding density of current and its effect on histopathology of the resected transurethral resection of bladder tumor (TURBT) chips. Aims: The aim of this study is to evaluate the histomorphological features in resected bladder tumors comparing bipolar versus conventional (monopolar) energy. Settings and Design: Inclusion criteria were patients with primary presentation of carcinoma urinary bladder undergoing TURBT. The patients with prior resections were excluded as these could jeopardize the results of cautery artifacts. Materials and Methods: From February 2010 to December 2011, 61 patients with primary carcinoma bladder and meeting our inclusion criteria were compared. Group 1 (n = 31) underwent bipolar-TURBT (B-TURBT) and Group 2 (n = 30) monopolar-TURBT (M-TURBT). Two pathologists, who were blinded to the form of electrocautery used, examined the resected tissue. The degree of cautery artifact in each specimen was recorded. The severity of the cautery artifact was graded as absent, mild, moderate, or severe. The mean age, tumor size, and resection time were recorded in both groups. Statistical Analysis Used: Data were analyzed using SPSS 16. Data were compared in between groups using paired t-test and Pearson's Chi-square test. The significance level was set at 0.05. Results: The mean age, tumor size, and resection time were similar in between the two groups. The pathologists had no obscurity in reaching a correct diagnosis in all cases. The cautery artifacts were graded as absent in 10 (32.2%) and 8 (26.67%), mild in 12 (38.7%) and 11 (36.67%), moderate in 5 (16.1%) and 7 (23.33%) and severe in 4 (12.9%) and 5 (16.66%) cases, respectively in Group 1 and 2. There was no statistically significant histomorphogical dissimilarity between specimens according to the type of cautery used. Conclusions: Bladder tissue obtained from B-TURBT is of equivalent

  20. [Recurrence of Well Differentiated Intrascrotal Liposarcoma in Retroperitoneum Five Years after Resection : A Case Report].

    PubMed

    Yoshinaga, Mitsuhiro; Sekii, Yosuke; Nakazawa, Shigeaki; Nakagawa, Masahiro; Kishikawa, Hidefumi; Nishimura, Kenji

    2017-01-01

    A 68-year-old man underwent an inguinal orchiectomy for a right testicular tumor and the pathological diagnosis was atypical lipomatous tumor. Nine years later, a resection procedure was performed for local recurrence. Five years after that second surgery, abdominal computed tomography (CT) findings revealed a low density mass 40 mm in size on the back side of the right kidney and enlarged fat in the retroperitoneal space. We performed a laparoscopic tumor resection under a diagnosis of lipoma or liposarcoma recurrence, and the pathological diagnosis was well differentiated liposarcoma. Treatment with pazopanib was started, as a CT examination showed that the tumor remained, after which we performed an open nephroureterectomy and resected the remaining tumor portion. Pazopanib treatment was continued and no obvious signs of recurrence were seen at 8 months after the most recent surgery. Although well differentiated liposarcoma usually recurs in the original tumor region, multicentric recurrence in other parts is possible.

  1. DNA helicases Sgs1 and BLM promote DNA double-strand break resection.

    PubMed

    Gravel, Serge; Chapman, J Ross; Magill, Christine; Jackson, Stephen P

    2008-10-15

    A key cellular response to DNA double-strand breaks (DSBs) is 5'-to-3' DSB resection by nucleases to generate regions of ssDNA that then trigger cell cycle checkpoint signaling and DSB repair by homologous recombination (HR). Here, we reveal that in the absence of exonuclease Exo1 activity, deletion or mutation of the Saccharomyces cerevisiae RecQ-family helicase, Sgs1, causes pronounced hypersensitivity to DSB-inducing agents. Moreover, we establish that this reflects severely compromised DSB resection, deficient DNA damage signaling, and strongly impaired HR-mediated repair. Furthermore, we show that the mammalian Sgs1 ortholog, BLM--whose deficiency causes cancer predisposition and infertility in people--also functions in parallel with Exo1 to promote DSB resection, DSB signaling and resistance to DSB-generating agents. Collectively, these data establish evolutionarily conserved roles for the BLM and Sgs1 helicases in DSB processing, signaling, and repair.

  2. Endoscopic Resection of the Lateral Ankle Bursa With Synovial Chondromatosis.

    PubMed

    Lui, Tun Hing

    2016-06-01

    Bursal chondromatosis is synovial chondromatosis of the bursae. It is a rare disease entity that can involve the adventitial bursa of the lateral ankle. Complete synovectomy, removal of loose bodies, and bursectomy comprise the treatment of choice. Detailed preoperative radiologic assessment and surgical planning are the keys to success. Any accompanying synovial chondromatosis of the ankle or subtalar joint or tenosynovial chondromatosis of the peroneal tendon sheath should be treated together with the bursectomy. Endoscopic bursectomy can be performed through the bursal portal. The proximal and distal peroneal tendoscopy portals serve as viewing portals. The resection of the diseased tissues should be performed in a step-by-step zonal manner. Complete synovectomy and removal of loose bodies should be performed before bursectomy. Internal drainage of the bursal sac into the peroneal tendon sheath may be indicated if the sac is adherent to the skin. It should only be performed after complete synovectomy and removal of loose bodies.

  3. Novel Genes Participating in the Formation of Prismatic and Nacreous Layers in the Pearl Oyster as Revealed by Their Tissue Distribution and RNA Interference Knockdown

    PubMed Central

    Koyama, Hiroki; Mizutani, Saeri; Ota, Ayaka; Osakabe, Yuki; Nagai, Kiyohito; Maeyama, Kaoru; Okamoto, Kikuhiko; Kanoh, Satoshi; Asakawa, Shuichi; Watabe, Shugo

    2014-01-01

    In our previous publication, we identified novel gene candidates involved in shell formation by EST analyses of the nacreous and prismatic layer-forming tissues in the pearl oyster Pinctada fucata. In the present study, 14 of those genes, including two known genes, were selected and further examined for their involvement in shell formation using the RNA interference. Molecular characterization based on the deduced amino acid sequences showed that seven of the novel genes encode secretory proteins. The tissue distribution of the transcripts of the genes, as analyzed by RT-PCR and in situ hybridization, was mostly consistent with those obtained by the EST analysis reported previously. Shells in the pearl oysters injected with dsRNAs targeting genes 000027, 000058, 000081, 000096, 000113 (nacrein), 000118, 000133 and 000411 (MSI60), which showed expression specific to the nacreous layer forming tissues, showed abnormal surface appearance in this layer. Individuals injected with dsRNAs targeting genes 000027, 000113 and 000133 also exhibited abnormal prismatic layers. Individuals injected with dsRNAs targeting genes 000031, 000066, 000098, 000145, 000194 and 000200, which showed expression specific to prismatic layer forming tissues, displayed an abnormal surface appearance in both the nacreous and prismatic layers. Taken together, the results suggest that the genes involved in prismatic layer formation might also be involved in the formation of the nacreous layers. PMID:24454739

  4. Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue

    PubMed Central

    Erami, Zahra; Herrmann, David; Warren, Sean C.; Nobis, Max; McGhee, Ewan J.; Lucas, Morghan C.; Leung, Wilfred; Reischmann, Nadine; Mrowinska, Agata; Schwarz, Juliane P.; Kadir, Shereen; Conway, James R.W.; Vennin, Claire; Karim, Saadia A.; Campbell, Andrew D.; Gallego-Ortega, David; Magenau, Astrid; Murphy, Kendelle J.; Ridgway, Rachel A.; Law, Andrew M.; Walters, Stacey N.; Grey, Shane T.; Croucher, David R.; Zhang, Lei; Herzog, Herbert; Hardeman, Edna C.; Gunning, Peter W.; Ormandy, Christopher J.; Evans, T.R. Jeffry; Strathdee, Douglas; Sansom, Owen J.; Morton, Jennifer P.; Anderson, Kurt I.; Timpson, Paul

    2015-01-01

    Summary E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments. PMID:26725115

  5. Secondary tethers after physeal bar resection: a common source of failure?

    PubMed

    Hasler, Carol Claudius; Foster, Bruce Kristian

    2002-12-01

    Despite a standardized operative technique and appropriate patient selection for physeal bar resection, a bar size less than 50% of the physis, and a prospective growth period greater than 2 years, failure may result. Limited growth because of poor function of the remaining physis and secondary tethers (incomplete resection or recurrence of the bar) may prevent reestablishment of growth or lead to its premature cessation. The current study investigated patients with insufficient restoration of growth by means of magnetic resonance imaging or computed tomography or both. Twenty-two patients had 24 physeal bar resections with interposition of autologous fat as the index procedure (Langenskiöld technique). Fourteen patients had only fair or poor results. Five patients had premature arrest of the affected physis with a postoperative growth period less than 1 year. Radiologic and clinical findings revealed bridge recurrence in four patients but no obvious reasons in the remaining five patients. Postoperative magnetic resonance imaging or computed tomography or both detected a secondary tether because of incomplete bar resection (one patient) or recurrence of the bar (four patients). Graft dislocation out of the resection cavity with an associated recurrence of the bar proved to be the underlying problem in three of the eight patients with bar recurrence. Magnetic resonance imaging is not only useful in preoperative mapping of physeal bars but also may help to explain failures after growth plate surgery.

  6. Resection Followed by Stereotactic Radiosurgery to Resection Cavity for Intracranial Metastases

    SciTech Connect

    Do, Ly Pezner, Richard; Radany, Eric; Liu An; Staud, Cecil; Badie, Benham

    2009-02-01

    Purpose: In patients who undergo resection of central nervous system metastases, whole brain radiotherapy (WBRT) is added to reduce the rates of recurrence and neurologic death. However, the risk of late neurotoxicity has led many patients to decline WBRT. We offered adjuvant stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) as an alternative to select patients with resected brain metastases. Methods and Materials: We performed a retrospective review of patients who underwent brain metastasis resection followed by SRS/SRT. WBRT was administered only as salvage treatment. Patients had one to four brain metastases. The dose was 15-18 Gy for SRS and 22-27.5 Gy in four to six fractions for SRT. Target margins were typically expanded by 1 mm for rigid immobilization and 3 mm for mask immobilization. SRS/SRT involved the use of linear accelerator radiosurgery using the IMRT 21EX or Helical Tomotherapy unit. Results: Between December 1999 and January 2007, 30 patients diagnosed with intracranial metastases were treated with resection followed by SRS or SRT to the resection cavity. Of the 30 patients, 4 (13.3%) developed recurrence in the resection cavity, and 19 (63%) developed recurrences in new intracranial sites. The actuarial 12-month survival rate was 82% for local recurrence-free survival, 31% for freedom from new brain metastases, 67% for neurologic deficit-free survival, and 51% for overall survival. Salvage WBRT was performed in 14 (47%) of the 30 patients. Conclusion: Our results suggest that for patients with newly diagnosed brain metastases treated with surgical resection, postoperative SRS/SRT to the resection cavity is a feasible option. WBRT can be reserved as salvage treatment with acceptable neurologic deficit-free survival.

  7. Optimizing treatment of hepatic metastases from colorectal cancer: Resection or resection plus ablation?

    PubMed

    Chiappa, Antonio; Bertani, Emilio; Zbar, Andrew P; Foschi, Diego; Fazio, Nicola; Zampino, Maria; Belluco, Claudio; Orsi, Franco; Della Vigna, Paolo; Bonomo, Guido; Venturino, Marco; Ferrari, Carlo; Biffi, Roberto

    2016-03-01

    The present study determines the oncologic outcome of the combined resection and ablation strategy for colorectal liver metastases (CRLM). Between January 1994 and December 2014, 360 patients underwent surgery for CRLM. There were 280 patients who underwent hepatic resection only (group 1) and 80 hepatic resection plus ablation (group 2). group 2 patients had a higher incidence of multiple metastases than group 1 cases (100% in group 2 vs. 28.2% in group 1; P<0.001) and bilobar involvement (76.5% in group 2 vs. 12.9% in group 1; P<0.001). Perioperative mortality was nil in either group with a higher postoperative complication rate amongst group 1 vs. group 2 cases (18 vs. 0, respectively). The median follow-up was 90 months (range, 1-180) with a 5-year overall survival for group 1 and group 2 of 49 and 80%, respectively (P=0.193). The median disease-free survival for patients with R0 resection was 50, 43 and 34% at 1, 2 and 3 years, respectively, and remained steadily higher (at 50%) in those patients treated with resection combined with ablation up to 5 years (P=0.069). The only intraoperative ablation failure was for a large lesion (≥5 cm). Our data support the use of intraoperative ablation when complete hepatic resection cannot be achieved.

  8. [Reoperations of rectal resection for recurrence after previous resection for rectosigmoid cancer].

    PubMed

    Paineau, J; Letessier, E; Hamy, A; Hamelin, E; Courant, O; Visset, J

    1993-12-01

    From June 1986 to December 1992, 16 patients (12 men and 4 women, 63 years-old [36 to 79]) who underwent a prior sphincter-saving resection for colorectal adenocarcinoma were operated on for locoregional recurrence with a surgical resection. Eight patients had a second anterior resection (5 colorectal, 2 coloanal and 1 ileoanal anastomosis), one a resection without anastomosis, and 7 an abdomino-perineal resection. Nine patients received an intraoperative irradiation (10 to 25 Gy). Excisions of surrounding organs were often necessary. Post-operative complications occurred in most of the patients. Excluding 3 post-operative deaths, 9 patients died of disease in a median of 12.9 months after surgery (range: 3 to 32 months). Four patients are still living 5 to 14 months after the second resection. There is little in the surgical literature dealing with these difficult surgical problem of which results are always uncertain. An earlier diagnosis of the recurrence would result in a more satisfactory procedure, but is difficult because of the limited possibilities of detection after surgical treatment and often external irradiation.

  9. Variability in splanchnic tissue oxygenation during preterm red blood cell transfusion given for symptomatic anaemia may reveal a potential mechanism of transfusion-related acute gut injury

    PubMed Central

    Bailey, Sean M.; Hendricks-Muñoz, Karen D.; Mally, Pradeep V.

    2015-01-01

    Background There is increasing evidence indicating an association between red blood cell (RBC) transfusions and necrotising enterocolitis (NEC) in preterm infants, especially late-onset NEC. This phenomenon is referred to as transfusion-related acute gut injury (TRAGI). One theory as to a pathophysiological mechanism is that transfusion may result in an ischemia-reperfusion injury to intestinal tissue. We tested the hypothesis that there is significantly greater variability during transfusion in splanchnic tissue oxygen saturation (SrSO2) than in cerebral tissue oxygen saturation (CrSO2). Materials and methods This was a prospective, observational study using near-infrared spectroscopy to monitor SrSO2 and CrSO2 in preterm neonates undergoing RBC transfusion for symptomatic anaemia. Mean, standard deviation, highest and lowest SrSO2 and CrSO2 values during each transfusion were determined. The greatest difference in SrSO2 and CrSO2 during each transfusion was calculated, along with the coefficient of variation. Results We studied 37 subjects. Throughout all transfusions, the mean SrSO2 was 45.6% ±13.8 and the mean CrSO2 was 65.4% ±6.9 (p<0.001). The variability of SrSO2 was significantly greater than that of CrSO2. Averaging data from all subjects, the greatest difference in SrSO2 was 43.8% ±13.4 compared with 23.3% ±7.6 for CrSO2 (p<0.001). The mean coefficient of variation in all transfusions was 20.5% for SrSO2 and 6.0% for CrSO2 (p<0.001). Increasing post-conceptional age did not affect SrSO2 variability (R2 =0.022; p=0.379), whereas CrSO2 variability during transfusion decreased with increasing post-conceptional age (R2=0.209; p=0.004). Discussion In preterm infants, there is a large degree of tissue oxygenation variability in splanchnic tissue during RBC transfusion and this does not change with increasing maturity. We speculate that these findings, combined with lower average tissue oxygenation, may demonstrate susceptibility of the preterm gut to TRAGI

  10. Spheno-Orbital Meningioma Resection and Reconstruction: The Role of Piezosurgery and Premolded Titanium Mesh

    PubMed Central

    Jung, Susana Heredero; Ferrer, Alicia Dean; Vela, Juan Solivera; Granados, Francisco Alamillos

    2011-01-01

    We present the clinical case of a patient with a spheno-orbital meningioma. Literature review of the treatment options, including the application of piezoelectric or ultrasound surgery and orbital reconstruction after meningioma resection, is also presented. Complete resection was performed by means of a frontotemporal craniotomy and an orbitozygomatic approach. Piezoelectric osteotomy was used around the optic nerve canal and the superior orbital fissure to minimize the damage to soft tissues. Orbital wall reconstruction was done using a titanium mesh previously premolded using a skull model. The superior orbital rim was reconstructed with calvarial bone grafts, and the sphenotemporal bone defect was covered with a titanium mesh cranioplasty. Ultrasonic vibrations to perform osteotomies in craniofacial surgery provide an interesting tool to reduce damage to surrounding soft tissues. Reconstruction of the roof and lateral orbital wall with premolded titanium meshes with a skull model is a safe and easy method to achieve a good orbital reconstruction and to avoid secondary sequelae. PMID:23205170

  11. A Sorghum bicolor expression atlas reveals dynamic genotype-specific expression profiles for vegetative tissues of grain, sweet and bioenergy sorghums

    SciTech Connect

    Shakoor, N; Nair, R; Crasta, O; Morris, G; Feltus, A; Kresovich, S

    2014-01-23

    Background: Effective improvement in sorghum crop development necessitates a genomics-based approach to identify functional genes and QTLs. Sequenced in 2009, a comprehensive annotation of the sorghum genome and the development of functional genomics resources is key to enable the discovery and deployment of regulatory and metabolic genes and gene networks for crop improvement. Results: This study utilizes the first commercially available whole-transcriptome sorghum microarray (Sorgh-WTa520972F) to identify tissue and genotype-specific expression patterns for all identified Sorghum bicolor exons and UTRs. The genechip contains 1,026,373 probes covering 149,182 exons (27,577 genes) across the Sorghum bicolor nuclear, chloroplast, and mitochondrial genomes. Specific probesets were also included for putative non-coding RNAs that may play a role in gene regulation (e. g., microRNAs), and confirmed functional small RNAs in related species (maize and sugarcane) were also included in our array design. We generated expression data for 78 samples with a combination of four different tissue types (shoot, root, leaf and stem), two dissected stem tissues (pith and rind) and six diverse genotypes, which included 6 public sorghum lines (R159, Atlas, Fremont, PI152611, AR2400 and PI455230) representing grain, sweet, forage, and high biomass ideotypes. Conclusions: Here we present a summary of the microarray dataset, including analysis of tissue-specific gene expression profiles and associated expression profiles of relevant metabolic pathways. With an aim to enable identification and functional characterization of genes in sorghum, this expression atlas presents a new and valuable resource to the research community.

  12. A Sorghum bicolor expression atlas reveals dynamic genotype-specific expression profiles for vegetative tissues of grain, sweet and bioenergy sorghums

    PubMed Central

    2014-01-01

    Background Effective improvement in sorghum crop development necessitates a genomics-based approach to identify functional genes and QTLs. Sequenced in 2009, a comprehensive annotation of the sorghum genome and the development of functional genomics resources is key to enable the discovery and deployment of regulatory and metabolic genes and gene networks for crop improvement. Results This study utilizes the first commercially available whole-transcriptome sorghum microarray (Sorgh-WTa520972F) to identify tissue and genotype-specific expression patterns for all identified Sorghum bicolor exons and UTRs. The genechip contains 1,026,373 probes covering 149,182 exons (27,577 genes) across the Sorghum bicolor nuclear, chloroplast, and mitochondrial genomes. Specific probesets were also included for putative non-coding RNAs that may play a role in gene regulation (e.g., microRNAs), and confirmed functional small RNAs in related species (maize and sugarcane) were also included in our array design. We generated expression data for 78 samples with a combination of four different tissue types (shoot, root, leaf and stem), two dissected stem tissues (pith and rind) and six diverse genotypes, which included 6 public sorghum lines (R159, Atlas, Fremont, PI152611, AR2400 and PI455230) representing grain, sweet, forage, and high biomass ideotypes. Conclusions Here we present a summary of the microarray dataset, including analysis of tissue-specific gene expression profiles and associated expression profiles of relevant metabolic pathways. With an aim to enable identification and functional characterization of genes in sorghum, this expression atlas presents a new and valuable resource to the research community. PMID:24456189

  13. Predictive analysis of optical ablation in several dermatological tumoral tissues

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, F.; Blanco-Gutiérrez, A.; Salas-García, I.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2013-06-01

    Optical techniques for treatment and characterization of biological tissues are revolutionizing several branches of medical praxis, for example in ophthalmology or dermatology. The non-invasive, non-contact and non-ionizing character of optical radiation makes it specially suitable for these applications. Optical radiation can be employed in medical ablation applications, either for tissue resection or surgery. Optical ablation may provide a controlled and clean cut on a biological tissue. This is particularly relevant in tumoral tissue resection, where a small amount of cancerous cells could make the tumor appear again. A very important aspect of tissue optical ablation is then the estimation of the affected volume. In this work we propose a complete predictive model of tissue ablation that provides an estimation of the resected volume. The model is based on a Monte Carlo approach for the optical propagation of radiation inside the tissue, and a blow-off model for tissue ablation. This model is applied to several types of dermatological tumoral tissues, specifically squamous cells, basocellular and infiltrative carcinomas. The parameters of the optical source are varied and the estimated resected volume is calculated. The results for the different tumor types are presented and compared. This model can be used for surgical planning, in order to assure the complete resection of the tumoral tissue.

  14. Bioluminescence imaging of chronic Trypanosoma cruzi infections reveals tissue-specific parasite dynamics and heart disease in the absence of locally persistent infection

    PubMed Central

    Lewis, Michael D; Fortes Francisco, Amanda; Taylor, Martin C; Burrell-Saward, Hollie; McLatchie, Alex P; Miles, Michael A; Kelly, John M

    2014-01-01

    Summary Chronic Trypanosoma cruzi infections lead to cardiomyopathy in 20–30% of cases. A causal link between cardiac infection and pathology has been difficult to establish because of a lack of robust methods to detect scarce, focally distributed parasites within tissues. We developed a highly sensitive bioluminescence imaging system based on T. cruzi expressing a novel luciferase that emits tissue-penetrating orange-red light. This enabled long-term serial evaluation of parasite burdens in individual mice with an in vivo limit of detection of significantly less than 1000 parasites. Parasite distributions during chronic infections were highly focal and spatiotemporally dynamic, but did not localize to the heart. End-point ex vivo bioluminescence imaging allowed tissue-specific quantification of parasite loads with minimal sampling bias. During chronic infections, the gastro-intestinal tract, specifically the colon and stomach, was the only site where T. cruzi infection was consistently observed. Quantitative PCR-inferred parasite loads correlated with ex vivo bioluminescence and confirmed the gut as the parasite reservoir. Chronically infected mice developed myocarditis and cardiac fibrosis, despite the absence of locally persistent parasites. These data identify the gut as a permissive niche for long-term T. cruzi infection and show that canonical features of Chagas disease can occur without continual myocardium-specific infection. PMID:24712539

  15. RNA-sequencing of a mouse-model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns

    PubMed Central

    Doktor, Thomas Koed; Hua, Yimin; Andersen, Henriette Skovgaard; Brøner, Sabrina; Liu, Ying Hsiu; Wieckowska, Anna; Dembic, Maja; Bruun, Gitte Hoffmann; Krainer, Adrian R.; Andresen, Brage Storstein

    2017-01-01

    Spinal Muscular Atrophy (SMA) is a neuromuscular disorder caused by insufficient levels of the Survival of Motor Neuron (SMN) protein. SMN is expressed ubiquitously and functions in RNA processing pathways that include trafficking of mRNA and assembly of snRNP complexes. Importantly, SMA severity is correlated with decreased snRNP assembly activity. In particular, the minor spliceosomal snRNPs are affected, and some U12-dependent introns have been reported to be aberrantly spliced in patient cells and animal models. SMA is characterized by loss of motor neurons, but the underlying mechanism is largely unknown. It is likely that aberrant splicing of genes expressed in motor neurons is involved in SMA pathogenesis, but increasing evidence indicates that pathologies also exist in other tissues. We present here a comprehensive RNA-seq study that covers multiple tissues in an SMA mouse model. We show elevated U12-intron retention in all examined tissues from SMA mice, and that U12-dependent intron retention is induced upon siRNA knock-down of SMN in HeLa cells. Furthermore, we show that retention of U12-dependent introns is mitigated by ASO treatment of SMA mice and that many transcriptional changes are reversed. Finally, we report on missplicing of several Ca2+ channel genes that may explain disrupted Ca2+ homeostasis in SMA and activation of Cdk5. PMID:27557711

  16. Comparison between thulium laser resection of prostate and transurethral plasmakinetic resection of prostate or transurethral resection of prostate

    PubMed Central

    DeCao, Hong; Wang, Jia; Huang, Yu; LiangLiu, Ren; JunLei, Hao; Gao, Liang; Tang, Zhuang; YingHu, Chun; Li, Xiang; JiuYuan, Hong; Dong, Qiang; Wei, Qiang

    2015-01-01

    Benign prostatic hyperplasia (BPH) is one of the most common diseases in middle-aged and elderly men. In the present study, we aimed to compare the efficacy and safety of thulium laser resection of the prostate (TMLRP) with either transurethral plasmakinetic resection of the prostate (TUPKP) or transurethral resection of the prostate (TURP). A literature search was performed, eventually, 14 studies involving 1587 patients were included. Forest plots were produced by using Revman 5.2.0 software. Our meta-analysis showed that operation time, decrease in hemoglobin level, length of hospital stay, catheterization time, and development of urethral stricture significantly differed, whereas the transitory urge incontinence rate, urinary tract infection rate, and recatheterization rate did not significantly differ between TMLRP and either TURP or TUPKP. The blood transfusion rate was significantly different between TMLRP and TURP, but not between TMLRP and TUPKP. In addition, the retrograde ejaculation rate between TMLRP and TURP did not significantly differ. At 1, 3, 6, and 12 months of postoperative follow-up, the maximum flow rate, post-void residual, quality of life, and International Prostate Symptom Score did not significantly differ among the procedures. Thus, the findings of this study indicate that TMLRP may be a safe and feasible alternative. PMID:26444930

  17. Comparison between thulium laser resection of prostate and transurethral plasmakinetic resection of prostate or transurethral resection of prostate.

    PubMed

    DeCao, Hong; Wang, Jia; Huang, Yu; LiangLiu, Ren; JunLei, Hao; Gao, Liang; Tang, Zhuang; YingHu, Chun; Li, Xiang; JiuYuan, Hong; Dong, Qiang; Wei, Qiang

    2015-10-07

    Benign prostatic hyperplasia (BPH) is one of the most common diseases in middle-aged and elderly men. In the present study, we aimed to compare the efficacy and safety of thulium laser resection of the prostate (TMLRP) with either transurethral plasmakinetic resection of the prostate (TUPKP) or transurethral resection of the prostate (TURP). A literature search was performed, eventually, 14 studies involving 1587 patients were included. Forest plots were produced by using Revman 5.2.0 software. Our meta-analysis showed that operation time, decrease in hemoglobin level, length of hospital stay, catheterization time, and development of urethral stricture significantly differed, whereas the transitory urge incontinence rate, urinary tract infection rate, and recatheterization rate did not significantly differ between TMLRP and either TURP or TUPKP. The blood transfusion rate was significantly different between TMLRP and TURP, but not between TMLRP and TUPKP. In addition, the retrograde ejaculation rate between TMLRP and TURP did not significantly differ. At 1, 3, 6, and 12 months of postoperative follow-up, the maximum flow rate, post-void residual, quality of life, and International Prostate Symptom Score did not significantly differ among the procedures. Thus, the findings of this study indicate that TMLRP may be a safe and feasible alternative.

  18. SPOROGENESIS UNDER ULTRAVIOLET RADIATION IN LAMINARIA DIGITATA (PHAEOPHYCEAE) REVEALS PROTECTION OF PHOTOSENSITIVE MEIOSPORES WITHIN SORAL TISSUE: PHYSIOLOGICAL AND ANATOMICAL EVIDENCE(1).

    PubMed

    Gruber, Ansgar; Roleda, Michael Y; Bartsch, Inka; Hanelt, Dieter; Wiencke, Christian

    2011-06-01

    To study the effect of different radiation conditions on sporogenesis of Laminaria digitata (Huds.) J. V. Lamour., excised disks were induced to form sporangia under PAR (P), PAR + ultraviolet-A (UVA) (PA), and PAR + UVA + ultraviolet-B (UVB) (PAB) conditions in the laboratory. Vitality of meiospores, released from sori induced under different radiation conditions in the laboratory and from sori of wild sporophytes acclimated to in situ solar radiation in the presence and absence of ultraviolet radiation (UVR), was measured in terms of their germination capacity. Sorus induction in disks of laboratory-grown sporophytes was not hampered under light supplemented with UVR, and sorus area was not significantly different among P, PA, and PAB. Vitality and germination rate of meiospores released from sori induced under different radiation treatments was comparable. Likewise, screening of UVR of the natural solar radiation did not promote higher germination rates of meiospores released from wild sporophytes. Germination rates were, however, higher in meiospores released from laboratory-induced sori compared to sori of wild sporophytes. Higher DNA damage (formation of cyclobutane pyrimidine dimers, CPDs) was observed in laboratory-grown nonsorus compared to sorus tissue, while CPDs were nondetectable in both sorus and nonsorus tissue of wild sporophytes. To explain the apparent protection of developing meiospores and the unexpected UV resistance of soral tissue, concurrent anatomical investigations of sporogenic tissue were performed. We observed the previously unreported existence of two types of sterile paraphysis cells. One type of paraphysis cells, the most frequent type, contained several red-fluorescing plastids. The other type, less frequently occurring, was completely filled with substances emitting blue fluorescence under violet excitation, presumably brown algal phenolic compounds (phlorotannins). Cells of this type were irregularly scattered within

  19. Highly aligned stromal collagen is a negative prognostic factor following pancreatic ductal adenocarcinoma resection

    PubMed Central

    Drifka, Cole R.; Loeffler, Agnes G.; Mathewson, Kara; Keikhosravi, Adib; Eickhoff, Jens C.; Liu, Yuming; Weber, Sharon M.

    2016-01-01

    Risk factors for pancreatic ductal adenocarcinoma (PDAC) progression after surgery are unclear, and additional prognostic factors are needed to inform treatment regimens and therapeutic targets. PDAC is characterized by advanced sclerosis of the extracellular matrix, and interactions between cancer cells, fibrillar collagen, and other stromal components play an integral role in progression. Changes in stromal collagen alignment have been shown to modulate cancer cell behavior and have important clinical value in other cancer types, but little is known about its role in PDAC and prognostic value. We hypothesized that the alignment of collagen is associated with PDAC patient survival. To address this, pathology-confirmed tissues from 114 PDAC patients that underwent curative-intent surgery were retrospectively imaged with Second Harmonic Generation (SHG) microscopy, quantified with fiber segmentation algorithms, and correlated to patient survival. The same tissue regions were analyzed for epithelial-to-mesenchymal (EMT), α-SMA, and syndecan-1 using complimentary immunohistostaining and visualization techniques. Significant inter-tumoral variation in collagen alignment was found, and notably high collagen alignment was observed in 12% of the patient cohort. Stratification of patients according to collagen alignment revealed that high alignment is an independent negative factor following PDAC resection (p = 0.0153, multivariate). We also found that epithelial expression of EMT and the stromal expression of α-SMA and syndecan-1 were positively correlated with collagen alignment. In summary, stromal collagen alignment may provide additional, clinically-relevant information about PDAC tumors and underscores the importance of stroma-cancer interactions. PMID:27776346

  20. Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma.

    PubMed

    Riazy, Maziar; Kalloger, Steve E; Sheffield, Brandon S; Peixoto, Renata D; Li-Chang, Hector H; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F

    2015-10-01

    Deficiencies in DNA mismatch repair have been associated with inferior response to 5-FU in colorectal cancer. Pancreatic ductal adenocarcinoma is similarly treated with pyrimidine analogs, yet the predictive value of mismatch repair status for response to these agents has not been examined in this malignancy. A tissue microarray with associated clinical outcome, comprising 254 resected pancreatic ductal adenocarcinoma patients was stained for four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Mismatch repair deficiency and proficiency was determined by the absence or presence of uniform nuclear staining in tumor cells, respectively. Cases identified as mismatch repair deficient on the tissue microarray were confirmed by immunohistochemistry on whole slide sections. Of the 265 cases, 78 (29%) received adjuvant treatment with a pyrimidine analog and 41 (15%) showed a mismatch repair-deficient immunoprofile. Multivariable disease-specific survival in the mismatch repair-proficient cohort demonstrated that adjuvant chemotherapy, regional lymph-node status, gender, and the presence of tumor budding were significant independent prognostic variables (P≤0.04); however, none of the eight clinico-pathologic covariates examined in the mismatch repair-deficient cohort were of independent prognostic significance. Univariable assessment of disease-specific survival revealed an almost identical survival profile for both treated and untreated patients with a mismatch repair-deficient profile, while treatment in the mismatch repair-proficient cohort conferred a greater than 10-month median disease-specific survival advantage over their untreated counterparts (P=0.0018). In this cohort, adjuvant chemotherapy with a pyrimidine analog conferred no survival advantage to mismatch repair-deficient pancreatic ductal adenocarcinoma patients. Mismatch repair immunoprofiling is a feasible predictive marker in pancreatic ductal adenocarcinoma patients, and further prospective

  1. One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients.

    PubMed

    Xiao, Zhifeng; Tang, Fengwu; Tang, Jiaguang; Yang, Huilin; Zhao, Yannan; Chen, Bing; Han, Sufang; Wang, Nuo; Li, Xing; Cheng, Shixiang; Han, Guang; Zhao, Changyu; Yang, Xiaoxiong; Chen, Yumei; Shi, Qin; Hou, Shuxun; Zhang, Sai; Dai, Jianwu

    2016-07-01

    The objective of this clinical study was to assess the safety and feasibility of the collagen scaffold, NeuroRegen scaffold, one year after scar tissue resection and implantation. Scar tissue is a physical and chemical barrier that prevents neural regeneration. However, identification of scar tissue is still a major challenge. In this study, the nerve electrophysiology method was used to distinguish scar tissue from normal neural tissue, and then different lengths of scars ranging from 0.5-4.5 cm were surgically resected in five complete chronic spinal cord injury (SCI) patients. The NeuroRegen scaffold along with autologous bone marrow mononuclear cells (BMMCs), which have been proven to promote neural regeneration and SCI recovery in animal models, were transplanted into the gap in the spinal cord following scar tissue resection. No obvious adverse effects related to scar resection or NeuroRegen scaffold transplantation were observed immediately after surgery or at the 12-month follow-up. In addition, patients showed partially autonomic nervous function improvement, and the recovery of somatosensory evoked potentials (SSEP) from the lower limbs was also detected. The results indicate that scar resection and NeuroRegen scaffold transplantation could be a promising clinical approach to treating SCI.

  2. Laparoscopic Resection of Symptomatic Gastric Diverticula

    PubMed Central

    Zelisko, Andrea; Rodriguez, John; El-Hayek, Kevin

    2014-01-01

    Gastric diverticula are rare and usually asymptomatic. This report, however, describes two examples of symptomatic gastric diverticula successfully treated by laparoscopic resection. Both patients were male and in their sixth decade of life. One patient was relatively healthy with no past medical history, whereas the other patient had chronic pain issues and at presentation was also undergoing evaluation for hyperaldosteronism. The patients presented with gastrointestinal symptoms, including nausea, emesis, abdominal pain, and change in bowel function. In both cases, a gastric diverticulum was identified by CT scan, and precise anatomic position was determined by upper endoscopy. After discussion with the treating teams, including a gastroenterologist and surgeon, surgical treatment and resection was elected. Successful laparoscopic removal was accomplished in both patients, and they were discharged home after tolerating liquid diets. Both patients reported resolution of their abdominal symptoms at follow-up. PMID:24680154

  3. Computed tomographic appearance of resectable pancreatic carcinoma

    SciTech Connect

    Itai, Y.; Araki, T.; Tasaka, A.; Maruyama, M.

    1982-06-01

    Thirteen patients with resectable pancreatic carcinoma were examined by computed tomography (CT). Nine had a mass, 2 had dilatation of the main pancreatic duct, 1 appeared to have ductal dilatation, and 1 had no sign of abnormality. Resectable carcinoma was diagnosed retrospectively in 8 cases, based on the following criteria: a mass with a distinct contour, frequently containing a tiny or irregular low-density area and accompanied by dilatation of the caudal portion of the main pancreatic duct without involvement of the large vessels, liver, or lymph nodes. Including unresectable cancer, chronic pancreatitis, and obstructive jaundice from causes other than cancer, the false-positive rate was less than 6%. However, a small cancer without change in pancreatic contour is difficult to detect with CT.

  4. Outcome after rectum or sigmoid resection: a review for gynecologists.

    PubMed

    Ret Dávalos, María Lorena; De Cicco, Carlo; D'Hoore, Andre; De Decker, Bert; Koninckx, Philippe Robert

    2007-01-01

    It remains unclear when to perform a discoid or segmental bowel resection for large endometriotic nodules with intestinal invasion. Moreover, endometriosis series are rather small to fully evaluate functional consequences of bowel resection. We therefore reviewed the incidence of leakage and functional problems after anterior and sigmoid resection as reported in the surgical literature albeit for other indications. Endoscopic resection clearly is feasible but requires an experienced surgeon. The incidence of leakage is not different after hand-sewn or stapled anastomosis, but is higher after a low rectum resection than after a sigmoid resection. Similarly, functional bowel problems are higher after a low rectum resection than after sigmoid resection. Low rectum resection in addition can be associated with functional bladder problems and sexual disturbances as anorgasmia. In conclusion, short- and long-term complications are much higher after a low rectum than after a sigmoid resection. This seems to be important in making the decision to perform a discoid or a segmental bowel resection for severe endometriosis.

  5. In-depth N-glycome profiling of paired colorectal cancer and non-tumorigenic tissues reveals cancer-, stage- and EGFR-specific protein N-glycosylation.

    PubMed

    Sethi, Manveen K; Kim, Hoguen; Park, Cheol Keun; Baker, Mark S; Paik, Young-Ki; Packer, Nicolle H; Hancock, William S; Fanayan, Susan; Thaysen-Andersen, Morten

    2015-10-01

    Glycomics may assist in uncovering the structure-function relationships of protein glycosylation and identify glycoprotein markers in colorectal cancer (CRC) research. Herein, we performed label-free quantitative glycomics on a carbon-liquid chromatography-tandem mass spectrometry-based analytical platform to accurately profile the N-glycosylation changes associated with CRC malignancy. N-Glycome profiling was performed on isolated membrane proteomes of paired tumorigenic and adjacent non-tumorigenic colon tissues from a cohort of five males (62.6 ± 13.1 y.o.) suffering from colorectal adenocarcinoma. The CRC tissues were typed according to their epidermal growth factor receptor (EGFR) status by western blotting and immunohistochemistry. Detailed N-glycan characterization and relative quantitation identified an extensive structural heterogeneity with a total of 91 N-glycans. CRC-specific N-glycosylation phenotypes were observed including an overrepresentation of high mannose, hybrid and paucimannosidic type N-glycans and an under-representation of complex N-glycans (P < 0.05). Sialylation, in particular α2,6-sialylation, was significantly higher in CRC tumors relative to non-tumorigenic tissues, whereas α2,3-sialylation was down-regulated (P < 0.05). CRC stage-specific N-glycosylation was detected by high α2,3-sialylation and low bisecting β1,4-GlcNAcylation and Lewis-type fucosylation in mid-late relative to early stage CRC. Interestingly, a novel link between the EGFR status and the N-glycosylation was identified using hierarchical clustering of the N-glycome profiles. EGFR-specific N-glycan signatures included high bisecting β1,4-GlcNAcylation and low α2,3-sialylation (both P < 0.05) relative to EGFR-negative CRC tissues. This is the first study to correlate CRC stage and EGFR status with specific N-glycan features, thus advancing our understanding of the mechanisms causing the biomolecular deregulation associated with CRC.

  6. Liver Resection in Children with Hepatic Neoplasms

    PubMed Central

    Randolph, Judson G.; Altman, R. Peter; Arensman, Robert M.; Matlak, Michael E.; Leikin, Sanford L.

    1978-01-01

    In the past ten years, 28 patients with primary tumors of the liver have been treated. There were 11 benign tumors, including four hamartomas, three patients with focal nodular hyperplasia, and two each with congenital cysts and hemangioma. Hamartomas and masses of focal nodular hyperplasia should be excised when possible, but both are benign lesions; therefore life threatening excisions at the porta hepatis should be avoided. Cysts are often resectable, but when occupying all lobes of the liver, they can be successfully managed by marsupialization into the free peritoneal cavity. If resectable, hemangiomas should be removed; when occupying most of the liver as they often do, patients may be subject to platelet trapping or to cardiac failure. In some instances these lesions have been controlled by steroids, radiation therapy or hepatic artery ligation. Of 17 malignant tumors seen, 12 proved to be hepatoblastomas. Nine of the 12 patients underwent liver resection, of whom four are cured, (33%). There were three children with hepatocellular carcinomas and two with embryonal rhabdomyosarcoma. One child from each of these groups is cured by surgical excision. At present the only known cures in children with primary malignant liver neoplasms have been achieved by operative removal. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4. PMID:206216

  7. Laparoscopic intersphincteric resection: indications and results.

    PubMed

    Scala, Dario; Niglio, Antonello; Pace, Ugo; Ruffolo, Fulvio; Rega, Daniela; Delrio, Paolo

    2016-03-01

    Surgical treatment of distal rectal cancer has long been based only on abdominoperineal excision, resulting in a permanent stoma and not always offering a definitive local control. Sphincter saving surgery has emerged in the last 20 years and can be offered also to patients with low lying tumours, provided that the external sphincter is not involved by the disease. An intersphincteric resection (ISR) is based on the resection of the rectum with a distal dissection proceeding into the space between the internal and the external anal sphincter. Originally described as an open procedure, it has also been developed with the laparoscopic approach, and also this technically demanding procedure is inscribed among those offered to the patient by a minimally invasive surgery. Indications have to be strict and patient selection is crucial to obtain both oncological and functional optimal results. The level of distal dissection and the extent of internal sphincter resected are chosen according to the distal margin of the tumour and is based on MRI findings: accurate imaging is therefore mandatory to better define the surgical approach. We here present our actual indications for ISR, results in terms of operative time, median hospital stay for ISR in our experience and review the updated literature.

  8. [Resection of intracardiac myxoma. Case report].

    PubMed

    Carmona-Delgado, Víctor Manuel; Deloya-Maldonado, Angélica María; Carranza-Bernal, María Lourdes; Hinojosa-Pérez, Arturo; Farías-Mayene, Leobardo

    2017-01-01

    Myxomas are the most common benign cardiac tumors, which are considered emergency surgery. The resection should not be delayed because 8-9% of affected patients may die due to intracardiac blood flow obstruction. We presente a clinical case of a 47 year old female, history of dyslipidemia. Disease starts with retrosternal oppression feeling, dyspnea on moderate exercise, dizziness, pain in joints hands. Arrhytmic heart sounds, diastolic mitral murmur II/IV, breth sounds present, no lymph. Laboratory: hemoglobin 11.0, leucocyte 9000, glucose 96 mg/dL, chest RX medium arch prominence cardiac silhouette. ECO transthoracic LVEF 60 %, with left atrial intracardiac tumor 13x11 cm, pedicle fixed the interatrial septum, the mitral valve bulges, with mild mitral valve. Half sternotomy is performed intracardiac tumor resection, pericardial placement interatrial with extracorporeal circulation support 65', aortic clamping time of 40'. Intracardiac tumor surgical findings interatrial septum fixed to left side, pedicle, rounded, yellow, multiloculated, soft, 13x10 cm in diameter. Histopathological diagnosis cardiac myxoma. We conclude that the tumor resection was carried in a timely manner with satisfactory evolution.

  9. Esophageal carcinoid tumor treated by endoscopic resection.

    PubMed

    Yagi, Makoto; Abe, Yasuhiko; Sasaki, Yu; Nomura, Eiki; Sato, Takeshi; Iwano, Daisuke; Yoshizawa, Kazuya; Sakuta, Kazuhiro; Kanno, Nana; Nishise, Syouichi; Ueno, Yoshiyuki

    2015-05-01

    The present report describes a rare case of esophageal carcinoid tumor that was treated by endoscopic resection. A 43-year-old woman underwent esophagogastroduodenoscopy at her family clinic for screening of the upper digestive tract and a small lesion resembling a submucosal tumor was detected in the lower esophagus. A biopsy sample from the lesion was diagnosed as esophageal carcinoid tumor and the patient visited our hospital for detailed examination. The tumor was approximately 3 mm in diameter and its surface appeared to be covered with normal squamous epithelium. The tumor had a shiny reddish surface without ulceration or erosion. Magnifying endoscopy with narrow-band imaging showed structures resembling reticular vessels under the epithelium. Endoscopic ultrasonography depicted the tumor as a low-echoic mass within the lamina propria. Computed tomography did not detect the tumor and no metastatic lesions were evident in other organs. With the patient's informed consent, the tumor was resected using endoscopic submucosal dissection, with a sufficient free margin in both the vertical and horizontal directions. Magnifying endoscopic examination showed the resected tumor to have abundant reticular vessels. Finally, the tumor was diagnosed immunopathologically as an esophageal carcinoid tumor (neuroendocrine cell tumor, grade 1), without lymphatic or vascular invasion.

  10. Endoscopic Endonasal Approach for Transclival Resection of a Petroclival Meningioma: A Technical Note

    PubMed Central

    Jean, Walter C; Anaizi, Amjad; DeKlotz, Timothy R

    2016-01-01

    The endoscopic endonasal transclival approach has been widely described for its use to resect clivus chordomas, but there have only been isolated reports of its use for petroclival meningiomas. These tumors are most often resected utilizing open transpetrosal approaches, but these operations, difficult even in the hands of dedicated skull base surgeons, are particularly challenging if the meningiomas are medially-situated and positioned mainly behind the clivus. For this subset of petroclival meningiomas, a transclival approach may be preferable. We report a meningioma resected via an endoscopic endonasal transclival technique. The patient was a 63-year-old man who presented originally for medical attention because of diplopia related to an abducens palsy on the left. A workup at that time revealed a meningioma contained entirely in the left cavernous sinus, and this was treated with stereotactic radiosurgery. His symptoms resolved and his meningioma was stable on MRI for several years after treatment. The patient was then lost to follow-up until 13 years after radiosurgery when he experienced intermittent diplopia again. At this point, workup revealed a large petroclival meningioma compressing the brainstem. He underwent a successful endoscopic endonasal transclival resection of this tumor. A demonstration of the step-by-step surgical technique, discussion of the nuances of the operation, and a comparison with the open transpetrosal approaches are included in our report. PMID:27433420

  11. Preservation of olfaction after unilateral endoscopic approach for resection of esthesioneuroblastoma.

    PubMed

    Wessell, Aaron; Singh, Ameet; Litvack, Zachary

    2014-08-01

    Objectives We present a case of olfactory preservation after a unilateral transcribriform transethmoidal endoscopic resection of esthesioneuroblastoma. We also discuss the oncologic results of endoscopic and transcranial approaches and describe the potential benefits and limitations of an endoscopic approach. Setting Single academic medical center. Participant and Design The clinical course of a 28-year-old patient who underwent endoscopic en bloc resection of esthesioneuroblastoma through a unilateral transcribriform transethmoidal approach was reviewed. Results Imaging demonstrated a left-sided nasal mass with cribriform plate involvement (Kadish C). Intraoperatively, the left olfactory bulb and epithelium were sacrificed. Negative frozen sections were obtained from the right olfactory epithelium and dura surrounding the right olfactory bulb. Reconstruction was performed using a multilayered closure of fascia, rigid buttress, and nasoseptal flap. Histology was consistent with esthesioneuroblastoma. Postoperative clinical evaluation, endoscopy, and magnetic resonance imaging demonstrated no evidence of residual or recurrent tumor at 18 months. The UPSIT smell testing revealed normal olfaction preoperatively, moderate microsomia at 3 months postoperatively, and mild microsomia at 18 months postoperatively. Conclusions Endoscopic resection of esthesioneuroblastoma has demonstrated similar oncologic control while reducing postoperative morbidity and mortality over transcranial approaches. This case reveals the potential to preserve olfaction while achieving en bloc endoscopic resection of early stage esthesioneuroblastoma.

  12. [A Case of Resected Lymph Node Recurrence of Cancer of the Papilla of Vater].

    PubMed

    Harano, Rina; Kusashio, Kimihiko; Yasutomi, Jun; Matsumoto, Masanari; Suzuki, Masaru; Iida, Ayako; Irabu, Shinichiro; Imamura, Namiko; Shirokane, Daizi; Udagawa, Ikuo

    2015-11-01

    We report the successful resection of lymph node recurrence of cancer of the papilla of Vater after pancreatoduodenectomy (PD). A 67-year-old man had undergone PD for adenocarcinoma of the papilla of Vater, and histopathological examination revealed well differentiated papillotubular adenocarcinoma, ly1, v0, T1, n (0), pStage ⅠB. One year after surgery, abdominal computed tomography revealed a mass at the left side of the residual inferior pancreaticoduodenal artery (IPDA). We resected the mass, which was diagnosed as lymph node recurrence of cancer of the papilla of Vater. The patient remains alive without any evidence of recurrence 5 years since the second operation. We suggest that complete resection of lymph node surrounding the IPDA is an important surgical procedure for cancer of the papilla of Vater. There still is only limited experience with resection for recurrence of cancer of the papilla of Vater, but our case shows that it may provide for long-term survival from recurrence of cancer of the papilla of Vater.

  13. A Qualitative Assessment of Human Cadavers Embalmed by Thiel's Method Used in Laparoscopic Training for Renal Resection

    ERIC Educational Resources Information Center

    Rai, Bhavan Prasad; Tang, Benjie; Eisma, Roos; Soames, Roger W.; Wen, Haitao; Nabi, Ghulam

    2012-01-01

    Human cadaveric tissue is the fundamental substrate for basic anatomic and surgical skills training. A qualitative assessment of the use of human cadavers preserved by Thiel's method for a British Association of Urological Surgeons--approved, advanced laparoscopic renal resection skills training course is described in the present study. Four…

  14. Solitary Metastasis to a Distant Lymph Node in the Descending Mesocolon After Primary Resection for Hepatocellular Carcinoma: Is Surgical Resection Valid?

    PubMed Central

    Aisu, Yuki; Furuyama, Hiroaki; Hori, Tomohide; Machimoto, Takafumi; Hata, Toshiyuki; Kadokawa, Yoshio; Kato, Shigeru; Ando, Yasuhisa; Uchida, Yuichiro; Yasukawa, Daiki; Kimura, Yusuke; Sasaki, Maho; Takamatsu, Yuichiro; Yoshimura, Tunehiro

    2016-01-01

    Patient: Female, 65 Final Diagnosis: Mesocolic lymph node metastasis of Hetpatocellular carcinoma Symptoms: None Medication: — Clinical Procedure: Partial resection of descending colon including metastatic lymph node Specialty: Surgery Objective: Rare disease Background: Lymph node metastasis of hepatocellular carcinoma is rare, and lymph nodes located on hepatic hilar and hepatoduodenal ligaments are primary targets. Metastasis to a mesocolic lymph node has not been reported previously. Case Report: A 65-year-old woman with liver cirrhosis underwent primary resection of hepatocellular carcinoma. Two and a half years later, tumor marker levels increased remarkably and imaging revealed a mesocolic mass. The tumor measured 27 mm in diameter and showed characteristic findings consistent with hepatocellular carcinoma in dynamic computed tomographic images, although the tumor was negative in fluorine-18-fluorodeoxyglucose positron emission tomographic images. A preoperative diagnosis of solitary metastasis to a mesocolic lymph node was made, and we elected to perform surgical resection, although therapeutic strategies for rare solitary extrahepatic metastasis are controversial. The tumor was located in the mesocolon nearly at the wall of the descending colon. Curative resection was performed and histopathological analysis confirmed metastatic hepatocellular carcinoma to a mesocolic lymph node. Tumor marker levels normalized immediately postoperatively. To date, the patient remains free from recurrence without adjuvant therapy. Conclusions: This is the first known case of solitary hepatocellular carcinoma metastasis to a distant mesocolic lymph node, successfully treated. Diagnosing solitary hepatocellular carcinoma metastases to distant lymph nodes can be difficult. Although the ideal therapeutic approach has not be defined, surgical resection of solitary metastatic lymph nodes may be beneficial in carefully selected cases. PMID:27904130

  15. Resection of Large Metachronous Liver Metastasis with Gastric Origin: Case Report and Review of the Literature

    PubMed Central

    Runcanu, Alexandru; Paun, Sorin; Negoi, Ruxandra Irina; Beuran, Mircea

    2016-01-01

    Introduction: Increasing evidence suggests that surgical resection may be offered to a subgroup of patients with liver metastasis of gastric adenocarcinoma. The aim of this case report is to illustrate the surgical resection of a single liver metachronous recurrence twelve months after a radical total gastrectomy for cancer. Case report: A 63-year-old male patient with an Eastern Cooperative Oncology Group performance status of 1 was referred to our hospital for a single, large liver metastasis, twelve months after a radical total gastrectomy and DII lymphadenectomy for upper third gastric adenocarcinoma. As the adjuvant treatment, the patient received 12 cycles of FOLFOX chemotherapy. During the present admission, the abdominal computed tomography (CT) revealed a single liver metastasis located in the segments 5 and 6, of 105/85 mm in diameter. Surgical resection by an open approach of liver metastasis was decided. We performed a non-anatomical liver resection, without inflow control due to significant peritoneal adhesions in the liver hilum secondary to the previous lymphadenectomy. The patient was discharged after seven days, with an uneventful recovery. Six months after the second surgical procedure, the patient developed a local liver recurrence. The surgical resection of the liver recurrence was performed, with no postoperative morbidities, and the patient was discharged after eight days. Three months after the latest surgery, the patient is under adjuvant chemotherapy, with no imagistic signs of further recurrences. Conclusions:  Hepatic resection for liver metastasis of gastric origin may offer satisfactory oncological outcomes in a very selected subgroup of patients. PMID:27843732

  16. Preoperative Portal Vein Embolization Tailored to Prepare the Liver for Complex Resections: Initial Experience

    SciTech Connect

    Baere, T. de Robinson, J. M.; Deschamps, F.; Rao, P.; Teriitheau, C.; Goere, D.; Elias, D.

    2010-10-15

    The purpose of this study was to evaluate the safety and efficacy of preoperative portal vein embolization (PVE) tailored to prepare the liver for complex and extended resections. During the past 5 years, 12 PVEs were performed in noncirrhotic patients with liver metastases from colon cancer (n = 10), choroidal melanoma (n = 1), and leiomyosarcoma (n = 1) to prepare complex anatomical liver resections in patients with small future remnant livers. These liver resections planned to preserve only segment IV in four patients, segments IV, V, and VIII in four patients, segments II, III, VI, and VII in three patients, and segments V and VI in one patient. PVE was performed under general anesthesia with a flow-guided injection of a mixture of cyanoacrylate and Lipiodol using a 5-Fr catheter. All portal branches feeding the liver segments to be resected were successfully embolized with cyanoacrylate except one, which was occluded with coils due to the risk of reflux with cyanoacrylate. After a mean of 32 days, CT volumetry revealed a mean hypertrophy of the unembolized liver of 47 {+-} 25% (range, 21-88%). Liver resections could be performed in 10 patients but were canceled in 2, due to the occurrence of a new hepatic tumor in one and an insufficiently increased volume in the other. Among the 10 patients who underwent the liver resection, 1 died of postoperative sepsis, 3 died 3 to 32 months after surgery, including 1 death unrelated to cancer, and 6 were alive after 6 to 36 months after surgery. In conclusion, in this preliminary report, PVE appears to be feasible and able to induce hypertrophy of the future remnant liver before a complex and extended hepatectomy. Further evaluation is needed in a larger cohort.

  17. Ongoing advances in quantitative PpIX fluorescence guided intracranial tumor resection (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Olson, Jonathan D.; Kanick, Stephen C.; Bravo, Jaime J.; Roberts, David W.; Paulsen, Keith D.

    2016-03-01

    Aminolevulinc-acid induced protoporphyrin IX (ALA-PpIX) is being investigated as a biomarker to guide neurosurgical resection of brain tumors. ALA-PpIX fluorescence can be observed visually in the surgical field; however, raw fluorescence emissions can be distorted by factors other than the fluorophore concentration. Specifically, fluorescence emissions are mixed with autofluorescence and attenuated by background absorption and scattering properties of the tissue. Recent work at Dartmouth has developed advanced fluorescence detection approaches that return quantitative assessments of PpIX concentration, which are independent of background optical properties. The quantitative fluorescence imaging (qFI) approach has increased sensitivity to residual disease within the resection cavity at the end of surgery that was not visible to the naked eye through the operating microscope. This presentation outlines clinical observations made during an ongoing investigation of ALA-PpIX based guidance of tumor resection. PpIX fluorescence measurements made in a wide-field hyperspectral imaging approach are co-registered with point-assessment using a fiber optic probe. Data show variations in the measured PpIX accumulation among different clinical tumor grades (i.e. high grade glioma, low grade glioma), types (i.e. primary tumors. metastases) and normal structures of interest (e.g. normal cortex, hippocampus). These results highlight the contrast enhancement and underscore the potential clinical benefit offered from quantitative measurements of PpIX concentration during resection of intracranial tumors.

  18. Correlation between nipple elevation and breast resection weight: How to preoperatively plan breast reduction.

    PubMed

    Moio, Mariagrazia; Schonauer, Fabrizio

    2015-08-01

    Breast hypertrophy is often associated with functional limitations. Beyond the aesthetic concerns, breast reduction can improve symptoms and self-esteem. In different countries, health-care system regulations have fixed the threshold for reimbursement in 500 g of predicted tissue resection for each breast. Different preoperative measurements have been proposed to predict breast-tissue weight to be removed, showing a variable correlation with post-operative evaluation. We describe a reliable, simple measurement to predict the quantity of breast reduction in grams, which can be applicable to any surgical technique. A total of 128 patients undergoing bilateral breast reduction were evaluated. The correlation between the preoperative nipple-areola complex (NAC) lift distance and the weight of removed breast tissue was tested with linear regression and Pearson's test. Other anthropometric measurements were tested as a control. The ratio between resected grams and lift distance was explored to find a multiplication coefficient to be used at preoperative planning. The mean resection weight was 686.65 g. The mean NAC-lift distance was 7.6 cm. Positive correlation between the NAC-lift distance and the weight of breast tissue removed was found (r: 0.87; p < 0.001). The mean weight of the removed breast tissue (g) per centimetre of NAC lift was 81 g/cm in the group between 6 and 12 cm and 70 g/cm in the group with >12 cm of lift distance. The NAC-lift distance is a single, objective, repeatable measure that can provide a reliable prediction of breast-tissue grams to be removed; it helps in classifying breast-reduction indications.

  19. Expression patterns of platypus defensin and related venom genes across a range of tissue types reveal the possibility of broader functions for OvDLPs than previously suspected.

    PubMed

    Whittington, Camilla M; Papenfuss, Anthony T; Kuchel, Philip W; Belov, Katherine

    2008-09-15

    The platypus, as an egg-laying mammal, displays an unusual mixture of reptilian and mammalian characteristics. It is also venomous, and further investigations into its little-studied venom may lead to the development of novel pharmaceuticals and drug targets and provide insights into the origins of mammalian venom. Here we investigate the expression patterns of antimicrobial genes called defensins, and also the venom peptides called defensin-like peptides (OvDLPs). We show, in the first expression study on any platypus venom gene, that the OvDLPs are expressed in a greater range of tissues than would be expected for genes with specific venom function, and thus that they may have a wider role than previously suspected.

  20. In vivo characterization of the role of tissue-specific translation elongation factor 1A2 in protein synthesis reveals insights into muscle atrophy.

    PubMed

    Doig, Jennifer; Griffiths, Lowri A; Peberdy, David; Dharmasaroja, Permphan; Vera, Maria; Davies, Faith J C; Newbery, Helen J; Brownstein, David; Abbott, Catherine M

    2013-12-01

    Translation elongation factor 1A2 (eEF1A2), uniquely among translation factors, is expressed specifically in neurons and muscle. eEF1A2-null mutant wasted mice develop an aggressive, early-onset form of neurodegeneration, but it is unknown whether the wasting results from denervation of the muscles, or whether the mice have a primary myopathy resulting from loss of translation activity in muscle. We set out to establish the relative contributions of loss of eEF1A2 in the different tissues to this postnatal lethal phenotype. We used tissue-specific transgenesis to show that correction of eEF1A2 levels in muscle fails to ameliorate the overt phenotypic abnormalities or time of death of wasted mice. Molecular markers of muscle atrophy such as Fbxo32 were dramatically upregulated at the RNA level in wasted mice, both in the presence and in the absence of muscle-specific expression of eEF1A2, but the degree of upregulation at the protein level was significantly lower in those wasted mice without transgene-derived expression of eEF1A2 in muscle. This provides the first in vivo confirmation that eEF1A2 plays an important role in translation. In spite of the inability of the nontransgenic wasted mice to upregulate key atrogenes at the protein level in response to denervation to the same degree as their transgenic counterparts, there were no measurable differences between transgenic and nontransgenic wasted mice in terms of weight loss, grip strength, or muscle pathology. This suggests that a compromised ability fully to execute the atrogene pathway in denervated muscle does not affect the process of muscle atrophy in the short term.

  1. [Four resections of metachronous liver metastases and lateral lymph node metastases of a rectal carcinoid tumor - a case report].

    PubMed

    Nakamoto, Takayuki; Koyama, Fumikazu; Nakagawa, Tadashi; Nakamura, Shinji; Ueda, Takeshi; Nishigori, Naoto; Inoue, Takashi; Kawasaki, Keijirou; Obara, Shinsaku; Fujii, Hisao; Nakajima, Yoshiyuki

    2014-11-01

    The authors present a case of rectal carcinoid tumor with lateral lymph node metastases and liver metastases that was successfully treated by 4 resections. A 70-year-old man was diagnosed with a rectal carcinoid tumor (20 mm in diameter) with submucosal (SM) invasion. Radical resection was performed at 25 months, 38 months, and 57 months, when abdominal computed tomography (CT) revealed metachronous liver metastases of the rectal carcinoid tumor. At 50 months, metachronous lateral lymph node metastases were also revealed. Three hepatectomies and a laparoscopic lateral lymph node dissection were performed. The patient is currently free of disease at 25 months after the last intervention.

  2. Distribution of the AQP4 water channel in normal human tissues: protein and tissue microarrays reveal expression in several new anatomical locations, including the prostate gland and seminal vesicles.

    PubMed

    Mobasheri, Ali; Marples, David; Young, Iain S; Floyd, Rachel V; Moskaluk, Christopher A; Frigeri, Antonio

    2007-01-01

    Aquaporins facilitate osmotically driven water movement across cell membranes. Aquaporin 4 (AQP4) is a major water channel in the central nervous system where it participates in cerebral water balance. AQP4 is also present in basolateral membranes of lower respiratory tract airway and renal collecting duct epithelial cells, gastric parietal cells and skeletal muscle cells. However, the distribution of AQP4 in many other tissues is still unknown. The aim of this study was to determine the expression and relative abundance of AQP4 in human Tissue MicroArrays (TMAs) and human protein microarrays by immunohistochemistry and chemiluminescence. In the central nervous system AQP4 was abundantly expressed in the cerebral cortex, cerebellar cortex (purkinje/granular layer), ependymal cell layer, hippocampus and spinal cord. Lower levels were detected in choroid plexus, white matter and meninges. In the musculoskeletal system AQP4 was highly expressed in the sarcolemma of skeletal muscle from the chest and neck. In the male genital system AQP4 was moderately expressed in seminiferous tubules, seminal vesicles, prostate and epidiymis. In the respiratory system AQP4 was moderately expressed in lung and bronchus. AQP expression was abundant in the kidney. In the gastrointestinal system AQP4 was moderately present in basolateral membranes of parietal cells at the base of gastric glands. AQP4 was also detected in salivary glands, adrenals, anterior pituitary, prostate and seminal vesicles. Human protein microarrays verified the TMA data. Our findings suggest that AQP4 is expressed more widely than previously thought in human organs and may be involved in prostatic and seminal fluid formation.

  3. Treatment of a skull-base giant cell tumor with endoscopic endonasal resection and denosumab: case report.

    PubMed

    Goto, Yukihiro; Furuno, Yuichi; Kawabe, Takuya; Ohwada, Kei; Tatsuzawa, Kazunori; Sasajima, Hiroyasu; Hashimoto, Naoya

    2017-02-01

    A 34-year-old man with a 1-week history of diplopia was referred to the authors' hospital. Neurological examination revealed left abducens nerve palsy. Computed tomography showed a lesion in the left sphenoid sinus involving the medial wall of the left internal carotid artery (ICA) and osteolytic change at the clivus bordering the lesion. Magnetic resonance imaging demonstrated an extensive soft-tissue mass occupying the left sphenoid sinus. Surgical intervention by the endoscopic transnasal method allowed most of the lesion to be removed. Only the portion attached to the medial wall of the ICA was not removed. Postoperatively, the lesion was diagnosed as a giant cell tumor (GCT) and the patient received 120 mg of subcutaneous denosumab every 4 weeks, with additional doses on Days 8 and 15 during the first month of therapy. MRI a week after starting denosumab revealed shrinkage of the initially fast-growing residual tumor. The patient was discharged upon completion of the third denosumab administration. GCT is an aggressive stromal tumor developing mainly in young adults. Complete resection is recommended for GCT in the literature. However, size and location of the CGT often limit this approach. Various adjuvant treatments for skull base GCTs have been reported, including radiation and chemotherapy. However, the roles of adjuvant therapies have yet to be clearly defined. Denosumab, a monoclonal antibody, was recently approved for GCT in several countries. Denosumab may permit less invasive treatments for patients with GCTs while avoiding deleterious outcomes, and may also limit disease progression and recurrence.

  4. Comparative analysis of resection tools suited for transoral robot-assisted surgery.

    PubMed

    Hoffmann, Thomas K; Schuler, Patrick J; Bankfalvi, Agnes; Greve, Jens; Heusgen, Lukas; Lang, Stephan; Mattheis, Stefan

    2014-05-01

    Introduction of transoral robot-assisted surgery (TORS) has a strong potential to facilitate surgical therapy of head and neck squamous cell cancer (HNSCC) by decreasing the indication for an external surgical approach. However, the availability of resection tools is limited and comparative studies in the context of TORS are not available. In the context of the newest da Vinci Si HD(®) robotic system, various dissection methods were compared in a surgical animal model using porcine tongue at three different sites representing mucosal, muscular and lymphatic tissue. Resection methods included (a) CO2 laser tube, (b) flexible fiber Tm:YAG laser, (c) monopolar blade, and (d) radio frequency (RF) needle. Specimens were formalin-fixed, paraffin-embedded, cut, and stained with haematoxylin-eosin. Dissected tissue was examined for the width of the incision as well as the individual coagulation zone of each tool at various tissue sites. In addition, instrument costs and performance were determined. The incisions made by the RF needle had the most favourable cutting width and also smaller coagulation defects, as opposed to other tools, granting the best preservation of tumour-adjacent structures and improved pathological assessment. Instrument performance was best evaluated for CO2 laser and RF needle, whereas financial expenses were lowest for RF needle and monopolar blade. Improvement and modification of resection tools for TORS become a relevant criterion in order to facilitate routine usage in the surgical therapy of HNSCC. A consequent decrease in surgical mortality and improved precision of surgical tumour resection could lead to a significant clinical growth potential of TORS.

  5. Assessment of the relationships between myocardial contractility and infarct tissue revealed by serial magnetic resonance imaging in patients with acute myocardial infarction.

    PubMed

    McComb, Christie; Carrick, David; McClure, John D; Woodward, Rosemary; Radjenovic, Aleksandra; Foster, John E; Berry, Colin

    2015-08-01

    Imaging changes in left ventricular (LV) volumes during the cardiac cycle and LV ejection fraction do not provide information on regional contractility. Displacement ENcoding with Stimulated Echoes (DENSE) is a strain-encoded cardiac magnetic resonance (CMR) technique that measures strain directly. We investigated the relationships between strain revealed by DENSE and the presence and extent of infarction in patients with recent myocardial infarction (MI). 50 male subjects were invited to undergo serial CMR within 7 days of MI (baseline) and after 6 months (follow-up; n = 47). DENSE and late gadolinium enhancement (LGE) images were acquired to enable localised regional quantification of peak circumferential strain (Ecc) and the extent of infarction, respectively. We assessed: (1) receiver operating characteristic (ROC) analysis for the classification of LGE, (2) strain differences according to LGE status (remote, adjacent, infarcted) and (3) changes in strain revealed between baseline and follow-up. 300 and 258 myocardial segments were available for analysis at baseline and follow-up respectively. LGE was present in 130/300 (43%) and 97/258 (38%) segments, respectively. ROC analysis revealed moderately high values for peak Ecc at baseline [threshold 12.8%; area-under-curve (AUC) 0.88, sensitivity 84%, specificity 78%] and at follow-up (threshold 15.8%; AUC 0.76, sensitivity 85%, specificity 64%). Differences were observed between remote, adjacent and infarcted segments. Between baseline and follow-up, increases in peak Ecc were observed in infarcted segments (median difference of 5.6%) and in adjacent segments (1.5%). Peak Ecc at baseline was indicative of the change in LGE status between baseline and follow-up. Strain-encoded CMR with DENSE has the potential to provide clinically useful information on contractility and its recovery over time in patients with MI.

  6. Anterior approach to the superior mesenteric artery by using nerve plexus hanging maneuver for borderline resectable pancreatic head carcinoma.

    PubMed

    Mizuno, Shugo; Isaji, Shuji; Tanemura, Akihiro; Kishiwada, Masashi; Murata, Yasuhiro; Azumi, Yoshinori; Kuriyama, Naohisa; Usui, Masanobu; Sakurai, Hiroyuki; Tabata, Masami

    2014-06-01

    To achieve R0 resection for pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head, complete resection of the retropancreatic nerve plexus around the superior mesenteric artery (SMA) is thought to be required. Twenty-five patients with borderline resectable right-sided PDAC were divided into two groups after neoadjuvant chemoradiotherapy: those with portal vein (PV) invasion alone (n = 12), and those with invasion of both PV and SMA (n = 13). A tape for guidance was passed in a space ventral to the SMA and behind the pancreatic parenchyma, followed by resection of the pancreatic parenchyma with the splenic vein. Another tape was passed behind the nerve plexus lateral to the hepatic artery and the SMA ventral to the inferior vena cava and the nerve plexus was dissected, resulting in complete resection of the nerve plexus around the SMA. Pathological findings revealed that the rates of R0, R01 (a margin less than 1 mm) and R1 were 58.3 %, 41.7 % and 0 % in PV group, and 53.8 %, 30.8 % and 15.4 % in PV/A group, respectively. The median survival time was 23.3 and 22.8 months in PV and PV/A groups, respectively. The plexus hanging maneuver for PDAC of the pancreatic head achieved complete resection of the retropancreatic nerve plexus around the SMA, helping to secure a negative surgical margin.

  7. [Ectopic mediastinal parathyroid tumor resected by video-assisted thoracic surgery with intraoperative methylene blue infusion; report of a case].

    PubMed

    Okagawa, Takehiko; Hiramatsu, Yoshinori

    2014-03-01

    We report a surgical case of ectopic mediastinal parathyroid tumor resected by video-assisted thoracic surgery with intraoperative methylene blue infusion. It is often difficult to detect ectopic mediastinal parathyroid tumor during the operation because the tumor is soft, small and buried under mediastinal tissue. After methylene blue 4 mg/kg intravenously administration, the tumor was gradually dyed blue and easily detected and resected by video-assisted thoracic surgery. It is useful of methylene blue for detection of ectopic mediastinal parathyroid tumor.

  8. Composite mesh and gluteal fasciocutaneous rotation flap for perineal hernia repair after abdominoperineal resection: a novel technique.

    PubMed

    Papadakis, Marios; Hübner, Gunnar; Bednarek, Marzena; Arafkas, Mohamed

    2017-03-01

    Perineal hernia is an uncommon complication following abdominoperineal rectum resection. Several surgical procedures have been proposed for perineal hernia repair, including perineal, laparoscopic and abdominal approaches. Repair techniques can be classified into primary suture techniques, mesh placements and repairs with autogenous tissue. We report a 68-year-old man with a perineal hernia, who underwent a pelvic floor reconstruction with a transperineal composite mesh and a gluteal fasciocutaneous rotation flap. We conclude that a combined approach with transperineal mesh reconstruction and gluteal fasciocutaneous flap could be an alternative choice in perineal hernia repair after abdominoperineal resection.

  9. A Systems Biology Approach Reveals the Dose- and Time-Dependent Effect of Primary Human Airway Epithelium Tissue Culture After Exposure to Cigarette Smoke In Vitro

    PubMed Central

    Mathis, Carole; Gebel, Stephan; Poussin, Carine; Belcastro, Vincenzo; Sewer, Alain; Weisensee, Dirk; Hengstermann, Arnd; Ansari, Sam; Wagner, Sandra; Peitsch, Manuel C; Hoeng, Julia

    2015-01-01

    To establish a relevant in vitro model for systems toxicology-based mechanistic assessment of environmental stressors such as cigarette smoke (CS), we exposed human organotypic bronchial epithelial tissue cultures at the air liquid interface (ALI) to various CS doses. Previously, we compared in vitro gene expression changes with published human airway epithelia in vivo data to assess their similarities. Here, we present a follow-up evaluation of these in vitro transcriptomics data, using complementary computational approaches and an integrated mRNA–microRNA (miRNA) analysis. The main cellular pathways perturbed by CS exposure were related to stress responses (oxidative stress and xenobiotic metabolism), inflammation (inhibition of nuclear factor-κB and the interferon gamma-dependent pathway), and proliferation/differentiation. Within post-exposure periods up to 48 hours, a transient kinetic response was observed at lower CS doses, whereas higher doses resulted in more sustained responses. In conclusion, this systems toxicology approach has potential for product testing according to “21st Century Toxicology”. PMID:25788831

  10. Gene Expression of Mesothelioma in Vinylidene Chloride-Exposed F344/N Rats Reveals Immune Dysfunction, Tissue Damage, and Inflammation Pathways

    PubMed Central

    Blackshear, Pamela E.; Pandiri, Arun R.; Nagai, Hiroaki; Bhusari, Sachin; Hong, Lily; Ton, Thai-Vu T.; Clayton, Natasha P.; Wyde, Michael; Shockley, Keith R.; Peddada, Shyamal D.; Gerrish, Kevin E.; Sills, Robert C.; Hoenerhoff, Mark J.

    2014-01-01

    A majority (~80%) of human malignant mesotheliomas are asbestos-related. However, non-asbestos risk factors (radiation, chemicals, genetic factors) account for up to 30% of cases. A recent two-year National Toxicology Program carcinogenicity bioassay showed that male F344/N rats exposed to the industrial toxicant vinylidene chloride (VDC) resulted in a marked increase in malignant mesothelioma. Global gene expression profiles of these tumors were compared to spontaneous mesotheliomas and the F344/N rat mesothelial cell line (Fred-PE) in order to characterize the molecular features and chemical-specific profiles of mesothelioma in VDC-exposed rats. As expected, mesotheliomas from control and vinylidene chloride-exposed rats shared pathways associated with tumorigenesis, including cellular and tissue development, organismal injury, embryonic development, inflammatory response, cell cycle regulation, and cellular growth and proliferation, while mesotheliomas from vinylidene chloride-exposed rats alone showed overrepresentation of pathways associated with pro-inflammatory pathways and immune dysfunction such as the NF-kB signaling pathway, IL-8 and IL-12 signaling, interleukin responses, Fc receptor signaling, and NK and DC signaling, as well as overrepresentation of DNA damage and repair. These data suggest that a chronic, proinflammatory environment associated with VDC exposure may exacerbate disturbances in oncogene, growth factor and cell cycle regulation, resulting in an increased incidence of mesothelioma. PMID:24958746

  11. A systems biology approach reveals the dose- and time-dependent effect of primary human airway epithelium tissue culture after exposure to cigarette smoke in vitro.

    PubMed

    Mathis, Carole; Gebel, Stephan; Poussin, Carine; Belcastro, Vincenzo; Sewer, Alain; Weisensee, Dirk; Hengstermann, Arnd; Ansari, Sam; Wagner, Sandra; Peitsch, Manuel C; Hoeng, Julia

    2015-01-01

    To establish a relevant in vitro model for systems toxicology-based mechanistic assessment of environmental stressors such as cigarette smoke (CS), we exposed human organotypic bronchial epithelial tissue cultures at the air liquid interface (ALI) to various CS doses. Previously, we compared in vitro gene expression changes with published human airway epithelia in vivo data to assess their similarities. Here, we present a follow-up evaluation of these in vitro transcriptomics data, using complementary computational approaches and an integrated mRNA-microRNA (miRNA) analysis. The main cellular pathways perturbed by CS exposure were related to stress responses (oxidative stress and xenobiotic metabolism), inflammation (inhibition of nuclear factor-κB and the interferon gamma-dependent pathway), and proliferation/differentiation. Within post-exposure periods up to 48 hours, a transient kinetic response was observed at lower CS doses, whereas higher doses resulted in more sustained responses. In conclusion, this systems toxicology approach has potential for product testing according to "21st Century Toxicology".

  12. Tetramers reveal IL-17-secreting CD4+ T cells that are specific for U1-70 in lupus and mixed connective tissue disease.

    PubMed

    Kattah, Nicole H; Newell, Evan W; Jarrell, Justin Ansel; Chu, Alvina D; Xie, Jianming; Kattah, Michael G; Goldberger, Ofir; Ye, Jessica; Chakravarty, Eliza F; Davis, Mark M; Utz, Paul J

    2015-03-10

    Antigen-specific CD4(+) T cells are implicated in the autoimmune disease systemic lupus erythematosus (SLE), but little is known about the peptide antigens that they recognize and their precise function in disease. We generated a series of MHC class II tetramers of I-E(k)-containing peptides from the spliceosomal protein U1-70 that specifically stain distinct CD4(+) T-cell populations in MRL/lpr mice. The T-cell populations recognize an epitope differing only by the presence or absence of a single phosphate residue at position serine(140). The frequency of CD4(+) T cells specific for U1-70(131-150):I-E(k) (without phosphorylation) correlates with disease severity and anti-U1-70 autoantibody production. These T cells also express RORγt and produce IL-17A. Furthermore, the U1-70-specific CD4(+) T cells that produce IL-17A are detected in a subset of patients with SLE and are significantly increased in patients with mixed connective tissue disease. These studies provide tools for studying antigen-specific CD4(+) T cells in lupus, and demonstrate an antigen-specific source of IL-17A in autoimmune disease.

  13. A modified UPR stress sensing system reveals a novel tissue distribution of IRE1/XBP1 activity during normal Drosophila development.

    PubMed

    Sone, Michio; Zeng, Xiaomei; Larese, Joseph; Ryoo, Hyung Don

    2013-05-01

    Eukaryotic cells respond to stress caused by the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum by activating the intracellular signaling pathways referred to as the unfolded protein response (UPR). In metazoans, UPR consists of three parallel branches, each characterized by its stress sensor protein, IRE1, ATF6, and PERK, respectively. In Drosophila, IRE1/XBP1 pathway is considered to function as a major branch of UPR; however, its physiological roles during the normal development and homeostasis remain poorly understood. To visualize IRE1/XBP1 activity in fly tissues under normal physiological conditions, we modified previously reported XBP1 stress sensing systems (Souid et al., Dev Genes Evol 217: 159-167, 2007; Ryoo et al., EMBO J 26: 242-252, 2007), based on the recent reports regarding the unconventional splicing of XBP1/HAC1 mRNA (Aragon et al., Nature 457: 736-740, 2009; Yanagitani et al., Mol Cell 34: 191-200, 2009; Science 331: 586-589, 2011). The improved XBP1 stress sensing system allowed us to detect new IRE1/XBP1 activities in the brain, gut, Malpighian tubules, and trachea of third instar larvae and in the adult male reproductive organ. Specifically, in the larval brain, IRE1/XBP1 activity was detected exclusively in glia, although previous reports have largely focused on IRE1/XBP1 activity in neurons. Unexpected glial IRE1/XBP1 activity may provide us with novel insights into the brain homeostasis regulated by the UPR.

  14. Differential molecular responses of rice and wheat coleoptiles to anoxia reveal novel metabolic adaptations in amino acid metabolism for tissue tolerance.

    PubMed

    Shingaki-Wells, Rachel N; Huang, Shaobai; Taylor, Nicolas L; Carroll, Adam J; Zhou, Wenxu; Millar, A Harvey

    2011-08-01

    Rice (Oryza sativa) and wheat (Triticum aestivum) are the most important starch crops in world agriculture. While both germinate with an anatomically similar coleoptile, this tissue defines the early anoxia tolerance of rice and the anoxia intolerance of wheat seedlings. We combined protein and metabolite profiling analysis to compare the differences in response to anoxia between the rice and wheat coleoptiles. Rice coleoptiles responded to anoxia dramatically, not only at the level of protein synthesis but also at the level of altered metabolite pools, while the wheat response to anoxia was slight in comparison. We found significant increases in the abundance of proteins in rice coleoptiles related to protein translation and antioxidant defense and an accumulation of a set of enzymes involved in serine, glycine, and alanine biosynthesis from glyceraldehyde-3-phosphate or pyruvate, which correlates with an observed accumulation of these amino acids in anoxic rice. We show a positive effect on wheat root anoxia tolerance by exogenous addition of these amino acids, indicating that their synthesis could be linked to rice anoxia tolerance. The potential role of amino acid biosynthesis contributing to anoxia tolerance in cells is discussed.

  15. Fast-track rehabilitation following video-assisted pulmonary sublobar wedge resection: A prospective randomized study

    PubMed Central

    Asteriou, Christos; Lazopoulos, Achilleas; Rallis, Thomas; Gogakos, Apostolos S; Paliouras, Dimitrios; Barbetakis, Nikolaos

    2016-01-01

    BACKGROUND: Postoperative morbidity and inhospital length of stay are considered major determinants of total health care expenditure associated with thoracic operations. The aim of this study was to prospectively evaluate the role of video-assisted thoracic surgery (VATS) compared to mini-muscle-sparing thoracotomy in facilitating early recovery and hospital discharge after pulmonary sublobar wedge resections. PATIENTS AND METHODS: A total number of 120 patients undergoing elective pulmonary sublobar wedge resection were randomly assigned to VATS (n = 60) or mini-muscle-sparing thoracotomy (n = 60). The primary endpoint was time to hospital discharge. Postoperative complications, cardiopulmonary morbidity and 30-day mortality served as secondary endpoints. RESULTS: Patients' baseline demographic and clinical data did not differ among study arms as well as the number of pulmonary segments resected and the morphology of the nodular lesions. Total hospital stay was significantly shorter in patients assigned to the thoracoscopic technique as opposed to those who were operated using the mini-muscle-sparing thoracotomy approach (4 ± 0.6 versus 4.4 ± 0.6 days respectively, P = 0.006). Multivariate analysis revealed that VATS approach was inversely associated with longer inhospital stay whereas the number of resected segments was positively associated with an increased duration of hospitalization. Patients in the VATS group were less likely to develop atelectasis (≥1 lobe) compared to those who underwent thoracotomy (0% versus 6.7% respectively, P = 0.042). Kaplan-Meier analysis revealed similar 30-day mortality rates in both study arms (Log-rank P = 0.560). CONCLUSION: VATS was associated with shorter duration of hospitalization positively affecting the patients' quality of life and satisfaction. Significant suppression of the total cost of recovery after thoracoscopic pulmonary resections is expected. PMID:27279390

  16. High expression of CD39 in gastric cancer reduces patient outcome following radical resection

    PubMed Central

    Cai, Xiao-Yan; Wang, Xue-Fei; Li, Jun; Dong, Jiang-Nan; Liu, Jiang-Qi; Li, Neng-Ping; Yun, Bei; Xia, Rong-Long; Qin, Jing; Sun, Yi-Hong

    2016-01-01

    Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), also known as cluster of differentiation (CD)39, is the rate-limiting enzyme in the generation of immunosuppressive adenosine and is important in tumor progression. The present study evaluated the expression of CD39+ and CD39+ forkhead box P3 (FoxP3)+ regulatory T (Treg) cells in gastric cancer (GC), and determined their prognostic roles in patients with GC following radical resection. It was observed that CD39 was expressed at significantly higher rates in tumor tissues as compared with paired peritumoral tissues. Overexpression of tumor CD39 was correlated with overall survival (OS). Furthermore, CD39 expression in GC tissues exhibited a prognostic role in OS. The CD39+ FoxP3+/FoxP3+ ratio in tumor tissues was higher than that in paired peritumoral tissues, and CD39+ FoxP3+ Treg cells were a better prognostic indicator than FoxP3+ Treg cells for OS. Collectively, our study indicates that overexpression of CD39 in GC is a predictor of poor outcome for GC patients following radical resection. CD39+ FoxP3+ Treg cells are a potential target for cancer immunotherapy. PMID:27895775

  17. Complex osteotomies vertebral column resection and decancellation.

    PubMed

    Obeid, Ibrahim; Bourghli, Anouar; Boissière, Louis; Vital, Jean-Marc; Barrey, Cédric

    2014-07-01

    Pedicle subtraction osteotomy (PSO) is nowadays widely used to treat sagittal imbalance. Some complex malalignment cases cannot be treated by a PSO, whereas the imbalance is coronal or mixed or the sagittal imbalance is major and cannot be treated by a single PSO. The aim of this article was to review these complex situations--coronal imbalance, mixed imbalance, two-level PSO, vertebral column resection, and vertebral column decancellation, and to focus on their specificities. It wills also to evoke the utility of navigation in these complex cases.

  18. Adjuvant therapy of resectable rectal cancer.

    PubMed

    Minsky, Bruce D

    2002-08-01

    The two conventional treatments for clinically resectable rectal cancer are surgery followed by postoperative combined modality therapy and preoperative combined modality therapy followed by surgery and postoperative chemotherapy. Preoperative therapy (most commonly combined modality therapy) has gained acceptance as a standard adjuvant therapy. The potential advantages of the preoperative approach include decreased tumor seeding, less acute toxicity, increased radiosensitivity due to more oxygenated cells, and enhanced sphincter preservation. There are a number of new chemotherapeutic agents that have been developed for the treatment of patients with colorectal cancer. Phase I/II trials examining the use of new chemotherapeutic agents in combination with pelvic radiation therapy are in progress.

  19. Harlequin Syndrome Following Resection of Mediastinal Ganglioneuroma

    PubMed Central

    Jeon, Yeong Jeong; Son, Jongbae; Cho, Jong Ho

    2017-01-01

    Harlequin syndrome is a rare disorder of the sympathetic nervous system characterized by unilateral facial flushing and sweating. Although its etiology is unknown, this syndrome appears to be a dysfunction of the autonomic nervous system. To the best of our knowledge, thus far, very few reports on perioperative Harlequin syndrome after thoracic surgery have been published in the thoracic surgical literature. Here, we present the case of a 6-year-old patient who developed this unusual syndrome following the resection of a posterior mediastinal mass. PMID:28382275

  20. Retrosigmoid approach for resection of petroclival meningioma.

    PubMed

    Nanda, Anil; Ambekar, Sudheer

    2014-01-01

    This video describes the classic retrosigmoid approach for the resection of petroclival lesions. In this procedure, a careful dissection of the tumor within the arachnoid plane from the neurovascular structures is described. The key steps in the procedure are outlined, and include positioning, tumor devascularization, decompression, dissection from lower cranial nerves, IV, V cranial nerves and the VII-VIII complex and from the brainstem and closure of the dura, bone flap and the incision. The video can be found here: http://youtu.be/DmutL7dBOxI .

  1. Acute appendicitis following endoscopic mucosal resection of cecal adenoma.

    PubMed

    Nemoto, Yukako; Tokuhisa, Junya; Shimada, Nagasato; Gomi, Tatsuya; Maetani, Iruru

    2015-07-21

    Endoscopic mucosal resection (EMR) allows the removal of flat or sessile lesions, laterally spreading tumors, and carcinoma of the colon or the rectum limited to the mucosa or the superficial submucosa. Acute appendicitis is the most common abdominal emergency requiring emergency surgery, and it is also a rare complication of diagnostic colonoscopy and therapeutic endoscopy, including EMR. In the case presented here, a 53-year-old female underwent colonoscopy due to a positive fecal occult blood test and was diagnosed with cecal adenoma. She was referred to our hospital and admitted for treatment. The patient had no other symptoms. EMR was performed, and 7 h after the surgery, the patient experienced right -lower abdominal pain. Laboratory tests performed the following day revealed a WBC count of 16000/mm(3), a neutrophil count of 14144/mm(3), and a C-reactive protein level of 2.20 mg/dL, indicating an inflammatory response. Computed tomography also revealed appendiceal wall thickening and swelling, so acute appendicitis following EMR was diagnosed. Antibiotics were initiated leading to total resolution of the symptoms, and the patient was discharged on the sixth post-operative day. Pathological analysis revealed a high-grade cecal tubular adenoma. Such acute appendicitis following EMR is extremely rare, and EMR of the cecum may be a rare cause of acute appendicitis.

  2. Does the method of resection affect the margins of tumours in the oral cavity? Prospective controlled study in pigs.

    PubMed

    George, Katherine S; Hyde, Nicholas C; Wilson, Philip; Smith, Graham I

    2013-10-01

    It is important to obtain tumour-free resection margins in patients with oral cancer. Pathological processing is known to cause tissue to shrink, which affects the reported margins, and it is postulated that the method of resection also has an effect. We marked standardised simulated lesions on the tongues of 15 live anaesthetised pigs and divided each lesion into four equal sections. They were resected each with a margin of 10mm using cutting diathermy, coagulative diathermy, Harmonic scalpel, and a conventional scalpel. After processing, the excision margins were measured. With cutting diathermy and coagulative diathermy, shrinkage of the soft tissues was minimal relative to the margin of the simulated lesion compared with the Harmonic scalpel (p=0.001) and conventional scalpel (p=0.001). Cutting diathermy and coagulative diathermy caused significant thermal damage (p=0.001). The method of resection affects the surgical margin. Diathermy resulted in thermal injury and denaturing of the underlying muscle, but there was less tissue contraction than when the Harmonic scalpel and conventional scalpel were used. The ethics committee approved the study, which was undertaken in a registered European Scientific Institute in Hamburg.

  3. Laparoscopic examination and resection for giant lipoma of the omentum: a case report and review of related literature.

    PubMed

    Shiroshita, Hidefumi; Komori, Yoko; Tajima, Masaaki; Bandoh, Toshio; Arita, Tsuyoshi; Shiraishi, Norio; Kitano, Seigo

    2009-10-01

    We report herein the case of a giant lipoma of the greater omentum that was treated by laparoscopic surgery. A 71-year-old male patient was admitted with a diagnosis of sigmoid colon cancer. During preoperative examination, a gallbladder stone and an intra-abdominal giant lipoma were accidentally diagnosed. Laparoscopic examination revealed a smooth-surfaced, giant yellow tumor at the lower border of the greater omentum that was unattached to the surrounding organs. After laparoscopic resection of the tumor and cholecystectomy, a 10-cm midline incision was made in the lower abdomen to remove the tumor and the gallbladder. We then performed a sigmoidectomy for sigmoid colon cancer through the same laparotomy. The resected tumor measured 29 x 19 x 3 cm and weighed 1250 g, and a histopathologic examination revealed a benign lipoma. Laparoscopic examination and resection of a giant lipoma of the omentum are particularly useful.

  4. Mutation of the palmitoylation site of estrogen receptor α in vivo reveals tissue-specific roles for membrane versus nuclear actions

    PubMed Central

    Adlanmerini, Marine; Solinhac, Romain; Abot, Anne; Fabre, Aurélie; Raymond-Letron, Isabelle; Guihot, Anne-Laure; Boudou, Frédéric; Sautier, Lucile; Vessières, Emilie; Kim, Sung Hoon; Lière, Philippe; Fontaine, Coralie; Krust, Andrée; Chambon, Pierre; Katzenellenbogen, John A.; Gourdy, Pierre; Shaul, Philip W.; Henrion, Daniel; Arnal, Jean-François; Lenfant, Françoise

    2014-01-01

    Estrogen receptor alpha (ERα) activation functions AF-1 and AF-2 classically mediate gene transcription in response to estradiol (E2). A fraction of ERα is targeted to plasma membrane and elicits membrane-initiated steroid signaling (MISS), but the physiological roles of MISS in vivo are poorly understood. We therefore generated a mouse with a point mutation of the palmitoylation site of ERα (C451A-ERα) to obtain membrane-specific loss of function of ERα. The abrogation of membrane localization of ERα in vivo was confirmed in primary hepatocytes, and it resulted in female infertility with abnormal ovaries lacking corpora lutea and increase in luteinizing hormone levels. In contrast, E2 action in the uterus was preserved in C451A-ERα mice and endometrial epithelial proliferation was similar to wild type. However, E2 vascular actions such as rapid dilatation, acceleration of endothelial repair, and endothelial NO synthase phosphorylation were abrogated in C451A-ERα mice. A complementary mutant mouse lacking the transactivation function AF-2 of ERα (ERα-AF20) provided selective loss of function of nuclear ERα actions. In ERα-AF20, the acceleration of endothelial repair in response to estrogen–dendrimer conjugate, which is a membrane-selective ER ligand, was unaltered, demonstrating integrity of MISS actions. In genome-wide analysis of uterine gene expression, the vast majority of E2-dependent gene regulation was abrogated in ERα-AF20, whereas in C451A-ERα it was nearly fully preserved, indicating that membrane-to-nuclear receptor cross-talk in vivo is modest in the uterus. Thus, this work genetically segregated membrane versus nuclear actions of a steroid hormone receptor and demonstrated their in vivo tissue-specific roles. PMID:24371309

  5. Antibodies to the Core Proteins of Nairobi Sheep Disease Virus/Ganjam Virus Reveal Details of the Distribution of the Proteins in Infected Cells and Tissues

    PubMed Central

    Lasecka, Lidia; Bin-Tarif, Abdelghani; Bridgen, Anne; Juleff, Nicholas; Waters, Ryan A.; Baron, Michael D.

    2015-01-01

    Nairobi sheep disease virus (NSDV; also called Ganjam virus in India) is a bunyavirus of the genus Nairovirus. It causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%. The virus is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus (CCHFV). Little is currently known about the biology of NSDV. We have generated specific antibodies against the virus nucleocapsid protein (N) and polymerase (L) and used these to characterise NSDV in infected cells and to study its distribution during infection in a natural host. Due to its large size and the presence of a papain-like protease (the OTU-like domain) it has been suggested that the L protein of nairoviruses undergoes an autoproteolytic cleavage into polymerase and one or more accessory proteins. Specific antibodies which recognise either the N-terminus or the C-terminus of the NSDV L protein showed no evidence of L protein cleavage in NSDV-infected cells. Using the specific anti-N and anti-L antibodies, it was found that these viral proteins do not fully colocalise in infected cells; the N protein accumulated near the Golgi at early stages of infection while the L protein was distributed throughout the cytoplasm, further supporting the multifunctional nature of the L protein. These antibodies also allowed us to gain information about the organs and cell types targeted by the virus in vivo. We could detect NSDV in cryosections prepared from various tissues collected post-mortem from experimentally inoculated animals; the virus was found in the mucosal lining of the small and large intestine, in the lungs, and in mesenteric lymph nodes (MLN), where NSDV appeared to target monocytes and/or macrophages. PMID:25905707

  6. Tissue-specific transcriptome analysis within the maturing sugarcane stalk reveals spatial regulation in the expression of cellulose synthase and sucrose transporter gene families.

    PubMed

    Casu, Rosanne E; Rae, Anne L; Nielsen, Janine M; Perroux, Jai M; Bonnett, Graham D; Manners, John M

    2015-12-01

    Sugarcane (Saccharum spp. hybrids) accumulates high concentrations of sucrose in its mature stalk and a considerable portion of carbohydrate metabolism is also devoted to cell wall synthesis and fibre production. We examined tissue-specific expression patterns to explore the spatial deployment of pathways responsible for sucrose accumulation and fibre synthesis within the stalk. We performed expression profiling of storage parenchyma, vascular bundles and rind dissected from a maturing stalk internode of sugarcane, identifying ten cellulose synthase subunit genes and examining significant differences in the expression of their corresponding transcripts and those of several sugar transporters. These were correlated with differential expression patterns for transcripts of genes encoding COBRA-like proteins and other cell wall metabolism-related proteins. The sugar transporters genes ShPST2a, ShPST2b and ShSUT4 were significantly up-regulated in storage parenchyma while ShSUT1 was up-regulated in vascular bundles. Two co-ordinately expressed groups of cell wall related transcripts were also identified. One group, associated with primary cell wall synthesis (ShCesA1, ShCesA7, ShCesA9 and Shbk2l3), was up-regulated in parenchyma. The other group, associated with secondary cell wall synthesis (ShCesA10, ShCesA11, ShCesA12 and Shbk-2), was up-regulated in rind. In transformed sugarcane plants, the ShCesA7 promoter conferred stable expression of green fluorescent protein preferentially in the storage parenchyma of the maturing stalk internode. Our results indicate that there is spatial separation for elevated expression of these important targets in both sucrose accumulation and cell wall synthesis, allowing for increased clarity in our understanding of sucrose transport and fibre synthesis in sugarcane.

  7. Antibodies to the core proteins of Nairobi sheep disease virus/Ganjam virus reveal details of the distribution of the proteins in infected cells and tissues.

    PubMed

    Lasecka, Lidia; Bin-Tarif, Abdelghani; Bridgen, Anne; Juleff, Nicholas; Waters, Ryan A; Baron, Michael D

    2015-01-01

    Nairobi sheep disease virus (NSDV; also called Ganjam virus in India) is a bunyavirus of the genus Nairovirus. It causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%. The virus is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus (CCHFV). Little is currently known about the biology of NSDV. We have generated specific antibodies against the virus nucleocapsid protein (N) and polymerase (L) and used these to characterise NSDV in infected cells and to study its distribution during infection in a natural host. Due to its large size and the presence of a papain-like protease (the OTU-like domain) it has been suggested that the L protein of nairoviruses undergoes an autoproteolytic cleavage into polymerase and one or more accessory proteins. Specific antibodies which recognise either the N-terminus or the C-terminus of the NSDV L protein showed no evidence of L protein cleavage in NSDV-infected cells. Using the specific anti-N and anti-L antibodies, it was found that these viral proteins do not fully colocalise in infected cells; the N protein accumulated near the Golgi at early stages of infection while the L protein was distributed throughout the cytoplasm, further supporting the multifunctional nature of the L protein. These antibodies also allowed us to gain information about the organs and cell types targeted by the virus in vivo. We could detect NSDV in cryosections prepared from various tissues collected post-mortem from experimentally inoculated animals; the virus was found in the mucosal lining of the small and large intestine, in the lungs, and in mesenteric lymph nodes (MLN), where NSDV appeared to target monocytes and/or macrophages.

  8. Multi-tissue stable isotope analysis and acoustic telemetry reveal seasonal variability in the trophic interactions of juvenile bull sharks in a coastal estuary.

    PubMed

    Matich, Philip; Heithaus, Michael R

    2014-01-01

    Understanding how natural and anthropogenic drivers affect extant food webs is critical to predicting the impacts of climate change and habitat alterations on ecosystem dynamics. In the Florida Everglades, seasonal reductions in freshwater flow and precipitation lead to annual migrations of aquatic taxa from marsh habitats to deep-water refugia in estuaries. The timing and intensity of freshwater reductions, however, will be modified by ongoing ecosystem restoration and predicted climate change. Understanding the importance of seasonally pulsed resources to predators is critical to predicting the impacts of management and climate change on their populations. As with many large predators, however, it is difficult to determine to what extent predators like bull sharks (Carcharhinus leucas) in the coastal Everglades make use of prey pulses currently. We used passive acoustic telemetry to determine whether shark movements responded to the pulse of marsh prey. To investigate the possibility that sharks fed on marsh prey, we modelled the predicted dynamics of stable isotope values in bull shark blood and plasma under different assumptions of temporal variability in shark diets and physiological dynamics of tissue turnover and isotopic discrimination. Bull sharks increased their use of upstream channels during the late dry season, and although our previous work shows long-term specialization in the diets of sharks, stable isotope values suggested that some individuals adjusted their diets to take advantage of prey entering the system from the marsh, and as such this may be an important resource for the nursery. Restoration efforts are predicted to increase hydroperiods and marsh water levels, likely shifting the timing, duration and intensity of prey pulses, which could have negative consequences for the bull shark population and/or induce shifts in behaviour. Understanding the factors influencing the propensity to specialize or adopt more flexible trophic interactions

  9. The characterization of the soybean polygalacturonase-inhibiting proteins (Pgip) gene family reveals that a single member is responsible for the activity detected in soybean tissues.

    PubMed

    D'Ovidio, R; Roberti, S; Di Giovanni, M; Capodicasa, C; Melaragni, M; Sella, L; Tosi, P; Favaron, F

    2006-08-01

    Polygalacturonase-inhibiting proteins (PGIPs) are leucine-rich repeat (LRR) proteins that inhibit fungal endopolygalacturonases (PGs). They are encoded by multigene families whose members show functional redundancy and subfunctionalization for recognition of fungal PGs. In order to expand the information on the structure and functional features of legume PGIP, we have isolated and characterized four members of the soybean Pgip gene family and determined the properties of the encoded protein products. Sequence analysis showed that these genes form two clusters: one cluster of about 5 kbp containing Gmpgip1 and Gmpgip2, and the other containing Gmpgip3 and Gmpgip4 within a 60 kb fragment of a separate BAC clone. Sequence diversification of the four members resides mainly in the xxLxLxx region that includes residues forming the beta-sheet B1. When compared with other legume Pgip genes, Gmpgip3 groups with the bean genes Pvpgip1 and Pvpgip2, suggesting that these genes are closer to the ancestral gene. At the protein level, only GmPGIP3 shows the capability to inhibit fungal PGs. The spectrum of inhibition of GmPGIP3 against eight different fungal PGs mirrors that of the PGIP purified from soybean tissues and is similar to that of the bean PvPGIP2, one of the most efficient inhibitors so far characterized. We also report that the four Gmpgip genes are differentially regulated after wounding or during infection with the fungal pathogen Sclerotinia sclerotiorum. Following fungal infection Gmpgip3 is up regulated promptly, while Gmpgip2 is delayed.

  10. 3-D illustration of network orientations of interstitial cells of Cajal subgroups in human colon as revealed by deep-tissue imaging with optical clearing.

    PubMed

    Liu, Yuan-An; Chung, Yuan-Chiang; Pan, Shien-Tung; Hou, Yung-Chi; Peng, Shih-Jung; Pasricha, Pankaj J; Tang, Shiue-Cheng

    2012-05-15

    Morphological changes of interstitial cells of Cajal (ICC) have been proposed to characterize motility disorders. However, a global view of the network orientations of ICC subgroups has not been established to illustrate their three-dimensional (3-D) architectures in the human colon. In this research, we integrate c-kit immunostaining, 3-D microscopy with optical clearing, and image rendering to present the location-dependent network orientations with high definition. Full-depth colonic tissues were obtained from colectomies performed for nonobstructing carcinoma. Specimens of colon wall were prepared away from the tumor site. C-kit and nuclear fluorescent staining were used to identify the ICC processes and cell body. Optical clearing was used to generate transparent colon specimens, which led to panoramic visualization of the fluorescence-labeled ICC networks at the myenteric plexus (ICC-MY), longitudinal (ICC-LM) and circular (ICC-CM) muscles, and submucosal boundary (ICC-SM) up to 300 μm in depth via confocal microscopy with subcellular level resolution. We observed four distinct network patterns: 1) periganglionic ICC-MY that connect with ICC-LM and ICC-CM, 2) plexuses of ICC-LM within the longitudinal muscle and extending toward the serosa, 3) repetitive and organized ICC-CM layers running parallel to the circular muscle axis and extending toward the submucosa, and 4) a condensed ICC-SM layer lining the submucosal border. Among the four patterns, the orderly aligned ICC-CM layers provide an appropriate target for quantitation. Our results demonstrate the location-dependent network orientations of ICC subgroups and suggest a practical approach for in-depth imaging and quantitative analysis of ICC in the human colon specimen.

  11. A case of distal extrahepatic cholangiocarcinoma with two positive resection margins

    PubMed Central

    Warner, Wayne A.; Ramcharan, Wesley; Harnanan, Dave; Umakanthan, Srikanth; Maharaj, Ravi

    2016-01-01

    Cholangiocarcinoma is an uncommon primary malignancy of the biliary tract that is challenging to diagnose and treat effectively due to its relatively silent and late clinical presentation. The present study reports a case of a 60-year-old male with distal extrahepatic cholangiocarcinoma with a 3-week history of painless obstructive jaundice symptoms and subjective weight loss. Imaging revealed an obstructing lesion in the common bile duct, just distal to the entrance of the cystic duct. Pathology revealed moderately differentiated cholangiocarcinoma with two positive proximal resection margins. The two positive resection margins presented a challenge during surgery and points to an urgent need for further studies to better illuminate diagnostic and therapeutic options for patients with similar clinicopathological presentation. PMID:27895774

  12. Curative resection of multiple gastrinomas aided by selective arterial secretin injection test and intraoperative secretin test.

    PubMed Central

    Imamura, M; Takahashi, K; Isobe, Y; Hattori, Y; Satomura, K; Tobe, T

    1989-01-01

    Recently a number of surgeons have recommended radical resection of gastrinomas in Zollinger-Ellison syndrome (ZES). We have developed a useful technique for preoperative localization of gastrinomas--the selective arterial secretin injection test (SASI)--and we recommend an intraoperative secretin test (IOS) for deciding the radicality of resection of gastrinomas. Here the results of SASI and IOS tests in 11 patients with ZES are examined and compared with the results of other techniques. The SASI test localized gastrinomas in all of the patients, while the sensitivity of ultrasonography, computed tomography, arteriography, or portal venous blood samplings was between 1/11 and 5/11. On the basis of the results of the SASI test, radical resection of gastrinoma was performed in four patients (three pancreatoduodenectomies and one extirpation). After pancreatoduodenectomy, immunohistologic study of the specimen revealed multiple microgastrinomas and lymph node metastases in two patients and the coexistence of a microgastrinoma and a gastinoma in one patient. The IOS test was useful in the estimation of the advisability of radicality, and in two patients total gastrectomy was not performed because of the results of the IOS test. These four patients are well and have returned to work, and their serum gastrin levels are below 35 pg/mL. Thus we believe SASI and IOS tests are helpful for planning curative resection of gastrinomas. Images Fig. 2. Fig. 3. Fig. 4. Fig. 7. PMID:2589884

  13. Intracranial germinoma in the pineal region arising after subtotal resection of epidermoid cyst: case report.

    PubMed

    Walker, Amanda J; Huynh-Le, Minh-Phuong; Nauen, David; Malayeri, Ashkan A; Jallo, George; Terezakis, Stephanie A

    2014-05-01

    We present an unusual case of a germinoma of the pineal region arising adjacent to an epidermoid cyst in a 16-year-old male. Initial imaging findings were classic for epidermoid cyst. The patient underwent two partial resections at an outside institution, each specimen demonstrating pure epidermoid cyst. Follow-up imaging over a period of 24 months showed an area of progressive contrast enhancement adjacent to the initial lesion, suggesting the development of a neoplasm. Given the area of contrast enhancement in addition to worsening headaches and visual changes, he underwent a third and final resection at our institution. Pathology revealed a mixed germ cell tumor with prominent germinoma component in addition to a well-differentiated epidermoid cyst. Details of his imaging and pathologic findings are presented, and possible explanations for these findings are explored, the most likely of which is lack of complete resection at the onset failed to identify the whole of the neoplasm. We conclude that pediatric epidermoid cysts of the pineal region should always receive close follow-up, particularly when total resection is not performed.

  14. Three-dimensional printing and computer navigation assisted hemipelvectomy for en bloc resection of osteochondroma

    PubMed Central

    Zhang, Yaqing; Wen, Lianjiang; Zhang, Jun; Yan, Guoliang; Zhou, Yue; Huang, Bo

    2017-01-01

    Abstract Rationale: Three-dimensional (3D) printed templates can be designed to match an individual's anatomy, allowing surgeons to refine preoperative planning. In addition, the use of computer navigation (NAV) is gaining popularity to improve surgical accuracy in the resection of pelvic tumors. However, its use in combination with 3D printing to assist complex pelvic tumor resection has not been reported. Patient concerns: A 36-year-old man presented with left-sided pelvic pain and a fast-growing mass. He also complained of a 3-month history of radiating pain and numbness in the lower left extremity. Diagnoses: A biopsy revealed an osteochondroma with malignant potential. This osteochondroma arises from the ilium and involves the sacrum and lower lumbar vertebrae. Interventions: Here, we describe a novel combined application of 3D printing and intraoperative NAV systems to guide hemipelvectomy for en-bloc resection of the osteochondroma. The 3D printed template is analyzed during surgical planning and guides the initial intraoperative bone work to improve surgical accuracy and efficiency, while a computer NAV system provides real-time imaging during the tumor removal to achieve adequate resection margins and minimize the likelihood of injury to adjacent critical structures. Outcomes: The tumor mass and the invaded spinal structures were removed en bloc. Lessons: The combined application of 3D printing and computer NAV may be useful for tumor targeting and safe osteotomies in pelvic tumor surgery. PMID:28328842

  15. [On the recurrence risk with partial larynx resections (author's transl)].

    PubMed

    Flach, M

    1978-06-01

    28 cases of recurrences after 127 vertical and horizontal partial larynx resections (22 per cent) were analysed. Unfavourable preconditions for partial resections are the affliction of the ary cartilage and arrest of vocal chord movility. The hemiresections according to Hautant have the heighest recidivation percentage (40 per cent) judging from the observations available. Radical operations after failured partial resections are uncertain as to their prognoses.

  16. Resection-reconstruction arthroplasty for giant cell tumor of distal radius

    PubMed Central

    Saikia, Kabul C; Borgohain, Munin; Bhuyan, Sanjeev K; Goswami, Sanjiv; Bora, Anjan; Ahmed, Firoz

    2010-01-01

    Background: Giant cell tumor (GCT) of the distal radius poses problems for reconstruction after resection. Several reconstructive procedures like vascularized and non-vascularized fibular graft, osteo-articular allograft, ceramic prosthesis and megaprosthesis are in use for substitution of the defect in the distal radius following resection. Most authors advocate wrist arthrodesis following resection of distal radius and non vascularized fibular graft. Here we have analyzed the results of aggressive benign GCTs of the distal radius treated by resection and reconstruction arthroplasty using autogenous non-vascularized fibular graft. Materials and Methods: Twenty-four cases of giant cell tumor of the distal radius (mean age 32 years, mean follow-up 6.6 years) treated by en-bloc resection and reconstruction arthroplasty using autogenous non-vascularized ipsilateral fibular graft with a minimum followup of two years have been included in this retrospective study. Nineteen cases were of Campanacci grade III and five were of Grade II recurrence. The mean resected length of the radius was 9.5 (8-12) cm. Routine radiographs and clinical assessments regarding pain, instability, recurrence, hand grip strength and functional status were done at regular intervals and functional results were assessed using (musculoskeletal tumor society) MSTS-87 scoring. Results: Early radiological union at host-graft junction was achieved at mean 12.5 weeks, (range 12-14 weeks) and solid incorporation with callus formation was observed in mean 29 weeks (range 28-32 weeks) in all the cases. Satisfactory range of motion (mean 63%, range 52-78%) of the wrist was achieved in 18 cases. Grip strength compared to the contralateral hand was found to be 67% (range 58-74%). Functional results were excellent in six cases (25%), good in 14 cases (58.3%) and four (16.7%) cases had fair results. Soft tissue recurrence was seen in one patient. The most commonly encountered complication was fibulo

  17. Local resection of the stomach for gastric cancer.

    PubMed

    Kinami, Shinichi; Funaki, Hiroshi; Fujita, Hideto; Nakano, Yasuharu; Ueda, Nobuhiko; Kosaka, Takeo

    2016-06-24

    The local resection of the stomach is an ideal method for preventing postoperative symptoms. There are various procedures for performing local resection, such as the laparoscopic lesion lifting method, non-touch lesion lifting method, endoscopic full-thickness resection, and laparoscopic endoscopic cooperative surgery. After the invention and widespread use of endoscopic submucosal dissection, local resection has become outdated as a curative surgical technique for gastric cancer. Nevertheless, local resection of the stomach in the treatment of gastric cancer in now expected to make a comeback with the clinical use of sentinel node navigation surgery. However, there are many issues associated with local resection for gastric cancer, other than the normal indications. These include gastric deformation, functional impairment, ensuring a safe surgical margin, the possibility of inducing peritoneal dissemination, and the associated increase in the risk of metachronous gastric cancer. In view of these issues, there is a tendency to regard local resection as an investigative treatment, to be applied only in carefully selected cases. The ideal model for local resection of the stomach for gastric cancer would be a combination of endoscopic full-thickness resection of the stomach using an ESD device and hand sutured closure using a laparoscope or a surgical robot, for achieving both oncological safety and preserved functions.

  18. Neuroendoscopic Resection of Intraventricular Tumors: A Systematic Outcomes Analysis

    PubMed Central

    Barber, Sean M.; Baskin, David

    2013-01-01

    Introduction. Though traditional microsurgical techniques are the gold standard for intraventricular tumor resection, the morbidity and invasiveness of microsurgical approaches to the ventricular system have galvanized interest in neuroendoscopic resection. We present a systematic review of the literature to provide a better understanding of the virtues and limitations of endoscopic tumor resection. Materials and Methods. 40 articles describing 668 endoscopic tumor resections were selected from the Pubmed database and reviewed. Results. Complete or near-complete resection was achieved in 75.0% of the patients. 9.9% of resected tumors recurred during the follow-up period, and procedure-related complications occurred in 20.8% of the procedures. Tumor size ≤ 2cm (P = 0.00146), the presence of a cystic tumor component (P < 0.0001), and the use of navigation or stereotactic tools during the procedure (P = 0.0003) were each independently associated with a greater likelihood of complete or near-complete tumor resection. Additionally, the complication rate was significantly higher for noncystic masses than for cystic ones (P < 0.0001). Discussion. Neuroendoscopic outcomes for intraventricular tumor resection are significantly better when performed on small, cystic tumors and when neural navigation or stereotaxy is used. Conclusion. Neuroendoscopic resection appears to be a safe and reliable treatment option for patients with intraventricular tumors of a particular morphology. PMID:24191196

  19. Treatment of Intravenous Leiomyomatosis with Cardiac Extension following Incomplete Resection

    PubMed Central

    Doyle, Mathew P.; Li, Annette; Villanueva, Claudia I.; Peeceeyen, Sheen C. S.; Cooper, Michael G.; Hanel, Kevin C.; Fermanis, Gary G.; Robertson, Greg

    2015-01-01

    Aim. Intravenous leiomyomatosis (IVL) with cardiac extension (CE) is a rare variant of benign uterine leiomyoma. Incomplete resection has a recurrence rate of over 30%. Different hormonal treatments have been described following incomplete resection; however no standard therapy currently exists. We review the literature for medical treatments options following incomplete resection of IVL with CE. Methods. Electronic databases were searched for all studies reporting IVL with CE. These studies were then searched for reports of patients with inoperable or incomplete resection and any further medical treatments. Our database was searched for patients with medical therapy following incomplete resection of IVL with CE and their results were included. Results. All studies were either case reports or case series. Five literature reviews confirm that surgery is the only treatment to achieve cure. The uses of progesterone, estrogen modulation, gonadotropin-releasing hormone antagonism, and aromatase inhibition have been described following incomplete resection. Currently no studies have reviewed the outcomes of these treatments. Conclusions. Complete surgical resection is the only means of cure for IVL with CE, while multiple hormonal therapies have been used with varying results following incomplete resection. Aromatase inhibitors are the only reported treatment to prevent tumor progression or recurrence in patients with incompletely resected IVL with CE. PMID:26783463

  20. Correlation coefficient mapping in fluorescence spectroscopy: tissue classification for cancer detection.

    PubMed

    Crowell, Ed; Wang, Gufeng; Cox, Jason; Platz, Charles P; Geng, Lei

    2005-03-01

    Correlation coefficient mapping has been applied to intrinsic fluorescence spectra of colonic tissue for the purpose of cancer diagnosis. Fluorescence emission spectra were collected of 57 colonic tissue sites in a range of 4 physiological conditions: normal (29), hyperplastic (2), adenomatous (5), and cancerous tissues (21). The sample-sample correlation was used to examine the ability of correlation coefficient mapping to determine tissue disease state. The correlation coefficient map indicates two main categories of samples. These categories were found to relate to disease states of the tissue. Sensitivity, selectivity, predictive value positive, and predictive value negative for differentiation between normal tissue and all other categories were all above 92%. This was found to be similar to, or higher than, tissue classification using existing methods of data reduction. Wavelength-wavelength correlation among the samples highlights areas of importance for tissue classification. The two-dimensional correlation map reveals absorption by NADH and hemoglobin in the samples as negative correlation, an effect not obvious from the one-dimensional fluorescence spectra alone. The integrity of tissue was examined in a time series of spectra of a single tissue sample taken after tissue resection. The wavelength-wavelength correlation coefficient map shows the areas of significance for each fluorophore and their relation to each other. NADH displays negative correlation to collagen and FAD, from the absorption of emission or fluorescence resonance energy transfer. The wavelength-wavelength correlation map for the decay set also clearly shows that there are only three fluorophores of importance in the samples, by the well-defined pattern of the map. The sample-sample correlation coefficient map reveals the changes over time and their impact on tissue classification. Correlation coefficient mapping proves to be an effective method for sample classification and cancer

  1. Use of Computed Tomography-Derived Prosthetics for Intraoperative Guidance of Tumor Resection.

    PubMed

    Chukwueke, Victor; Vercler, Christian J; Ranganathan, Kavitha; Kline, Stephanie; Buchman, Steven R

    2016-05-01

    Preoperative computed tomography (CT)-derived design and modeling provides a useful guide for a more accurate reconstruction of a variety of complex maxillofacial deformities. While the use of three-dimensional CT imaging has focused mainly on bony reconstruction, the use of this technique to facilitate soft tissue reconstruction represents an important innovation that can assist surgeons with preoperative planning and intraoperative decision-making. In this study, the authors report the novel use of three-dimensional CT scan modeling to facilitate the resection of a large maxillofacial neurofibroma in a patient with neurofibromatosis. In conjunction with an anaplastologist, the combined use of tangible models and aesthetic judgments significantly optimizes the quality of the initial resection and subsequent reconstruction. By utilizing an interdisciplinary approach, it is possible to achieve optimal symmetry in the setting of complex maxillofacial deformities.

  2. Neoadjuvant treatment for resectable pancreatic adenocarcinoma

    PubMed Central

    Wong, John; Solomon, Naveenraj L; Hsueh, Chung-Tsen

    2016-01-01

    Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress. PMID:26862486

  3. Surgical Resectability of Skull Base Meningiomas

    PubMed Central

    GOTO, Takeo; OHATA, Kenji

    2016-01-01

    With recent advances in surgical technology such as preoperative imaging, neuro-monitoring, and surgical instruments, the surgical resectability of intracranial meningiomas has increased over the last two decades. This study reviewed clinical articles regarding the surgical treatment of meningiomas to clarify the role of surgical excision, with a focus on skull base meningiomas. We sub-classified clinical articles about skull base meningiomas into two categories (anterior and middle fossa meningiomas; and posterior fossa meningiomas) and reviewed papers in each category. In cases with anterior and middle fossa meningiomas, surgical resectability has reached a sufficient level to maximize functional preservation. In cases of posterior fossa meningioma, however, surgical respectability remains insufficient even with full use of recent surgical modalities. Continuous refining of operative procedures is required to obtain more satisfactory outcomes, especially for posterior fossa meningioma. In addition, recent long-term outcomes of stereotactic radiosurgery (SRS) were acceptable for controlling the skull base meningiomas. Therefore, combination with surgical excision and SRS should be considered in complicated skull base meningiomas. PMID:27076382

  4. Hysteroscopic Transcervical Resection of Uterine Septum

    PubMed Central

    Shi, Xiaoyan; Hua, Xiangdong; Gu, Xiaoyan; Yang, Dazhen

    2013-01-01

    Objective: To explore the method of diagnosis for uterine septum and the clinical effect of hysteroscopic transcervical resection of the septum. Methods: One-hundred ninety cases of patients with uterine septum who were diagnosed and treated at our hospital during 2007–2011 were selected, and their general information, perioperative status, postoperative recovery treatment, and postoperative pregnancy rates were statistically analyzed. Results: All 190 patients were cured with one surgery, with an average hysteroscopic operating time of 22.60 ± 10.67 minutes and intraoperative blood loss of 15.74 ± 9.64 mL. There were no complications such as uterine perforation, water intoxication, infection, or heavy bleeding. Among the 115 patients that we followed up, 86 became pregnant and delivered infants, 81 of which were born at term and 5 that were born premature. Conclusion: The combination of hysteroscopy and laparoscopy is still the most reliable method for the diagnosis of uterine septum. With a shorter operative time, less blood loss, a significantly increased postoperative pregnancy rate and live birth rate, and a significantly lower spontaneous abortion rate, transcervical resection of the septum was the preferred method for the treatment of uterine septum, and surgical instruments and skills were critical to the prognosis of uterine septum. PMID:24398191

  5. Transgenic analysis of sugar beet xyloglucan endo-transglucosylase/hydrolase Bv-XTH1 and Bv-XTH2 promoters reveals overlapping tissue-specific and wound-inducible expression profiles.

    PubMed

    Dimmer, Emily; Roden, Laura; Cai, Daguang; Kingsnorth, Crawford; Mutasa-Göttgens, Effie

    2004-03-01

    The identification and analysis of tissue-specific gene regulatory elements will improve our knowledge of the molecular mechanisms that control the growth and development of different plant tissues and offer potentially useful tools for the genetic engineering of plants. A polymerase chain reaction (PCR)-based 5'-genome walk from sequences of an isolated sugar beet xyloglucan endo-transglucosylase hydrolase (XTH) gene led to the isolation of two independent upstream fragments. They were 1332 and 2163 base pairs upstream of the XTH ATG start site, respectively. In vivo transgenic assays in sugar beet hairy roots and Arabidopsis thaliana revealed that both fragments had promoter function and, in A. thaliana, directed expression in vascular tissues within the root, leaves and petals. Promoter activity was also observed in the leaf trichomes and within rapidly expanding stem internodes. Expression driven by both promoters was found to be wound inducible. Overall, the spatial and temporal expression pattern of these promoters suggested that the corresponding Bv-XTH genes (designated Bv-XTH1 and Bv-XTH2) may be involved in secondary cell wall formation. This work provides new insights on molecular mechanisms that could be exploited for the genetic engineering of sugar beet crops.

  6. Identification and Comparative Analysis of Differential Gene Expression in Soybean Leaf Tissue under Drought and Flooding Stress Revealed by RNA-Seq.

    PubMed

    Chen, Wei; Yao, Qiuming; Patil, Gunvant B; Agarwal, Gaurav; Deshmukh, Rupesh K; Lin, Li; Wang, Biao; Wang, Yongqin; Prince, Silvas J; Song, Li; Xu, Dong; An, Yongqiang C; Valliyodan, Babu; Varshney, Rajeev K; Nguyen, Henry T

    2016-01-01

    Drought and flooding are two major causes of severe yield loss in soybean worldwide. A lack of knowledge of the molecular mechanisms involved in drought and flood stress has been a limiting factor for the effective management of soybeans; therefore, it is imperative to assess the expression of genes involved in response to flood and drought stress. In this study, differentially expressed genes (DEGs) under drought and flooding conditions were investigated using Illumina RNA-Seq transcriptome profiling. A total of 2724 and 3498 DEGs were identified under drought and flooding treatments, respectively. These genes comprise 289 Transcription Factors (TFs) representing Basic Helix-loop Helix (bHLH), Ethylene Response Factors (ERFs), myeloblastosis (MYB), No apical meristem (NAC), and WRKY amino acid motif (WRKY) type major families known to be involved in the mechanism of stress tolerance. The expression of photosynthesis and chlorophyll synthesis related genes were significantly reduced under both types of stresses, which limit the metabolic processes and thus help prolong survival under extreme conditions. However, cell wall synthesis related genes were up-regulated under drought stress and down-regulated under flooding stress. Transcript profiles involved in the starch and sugar metabolism pathways were also affected under both stress conditions. The changes in expression of genes involved in regulating the flux of cell wall precursors and starch/sugar content can serve as an adaptive mechanism for soybean survival under stress conditions. This study has revealed the involvement of TFs, transporters, and photosynthetic genes, and has also given a glimpse of hormonal cross talk under the extreme water regimes, which will aid as an important resource for soybean crop improvement.

  7. Identification and Comparative Analysis of Differential Gene Expression in Soybean Leaf Tissue under Drought and Flooding Stress Revealed by RNA-Seq

    PubMed Central

    Chen, Wei; Yao, Qiuming; Patil, Gunvant B.; Agarwal, Gaurav; Deshmukh, Rupesh K.; Lin, Li; Wang, Biao; Wang, Yongqin; Prince, Silvas J.; Song, Li; Xu, Dong; An, Yongqiang C.; Valliyodan, Babu; Varshney, Rajeev K.; Nguyen, Henry T.

    2016-01-01

    Drought and flooding are two major causes of severe yield loss in soybean worldwide. A lack of knowledge of the molecular mechanisms involved in drought and flood stress has been a limiting factor for the effective management of soybeans; therefore, it is imperative to assess the expression of genes involved in response to flood and drought stress. In this study, differentially expressed genes (DEGs) under drought and flooding conditions were investigated using Illumina RNA-Seq transcriptome profiling. A total of 2724 and 3498 DEGs were identified under drought and flooding treatments, respectively. These genes comprise 289 Transcription Factors (TFs) representing Basic Helix-loop Helix (bHLH), Ethylene Response Factors (ERFs), myeloblastosis (MYB), No apical meristem (NAC), and WRKY amino acid motif (WRKY) type major families known to be involved in the mechanism of stress tolerance. The expression of photosynthesis and chlorophyll synthesis related genes were significantly reduced under both types of stresses, which limit the metabolic processes and thus help prolong survival under extreme conditions. However, cell wall synthesis related genes were up-regulated under drought stress and down-regulated under flooding stress. Transcript profiles involved in the starch and sugar metabolism pathways were also affected under both stress conditions. The changes in expression of genes involved in regulating the flux of cell wall precursors and starch/sugar content can serve as an adaptive mechanism for soybean survival under stress conditions. This study has revealed the involvement of TFs, transporters, and photosynthetic genes, and has also given a glimpse of hormonal cross talk under the extreme water regimes, which will aid as an important resource for soybean crop improvement. PMID:27486466

  8. High-frequency oscillations, extent of surgical resection, and surgical outcome in drug-resistant focal epilepsy

    PubMed Central

    Haegelen, Claire; Perucca, Piero; Châtillon, Claude-Edouard; Andrade-Valença, Luciana; Zelmann, Rina; Jacobs, Julia; Collins, D. Louis; Dubeau, François; Olivier, André; Gotman, Jean

    2013-01-01

    Summary Purpose Removal of areas generating high-frequency oscillations (HFOs) recorded from the intracerebral electroencephalography (iEEG) of patients with medically intractable epilepsy has been found to be correlated with improved surgical outcome. However, whether differences exist according to the type of epilepsy is largely unknown. We performed a comparative assessment of the impact of removing HFO-generating tissue on surgical outcome between temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). We also assessed the relationship between the extent of surgical resection and surgical outcome. Methods We studied 30 patients with drug-resistant focal epilepsy, 21 with TLE and 9 with ETLE. Two thirds of the patients were included in a previous report and for these, clinical and imaging data were updated and follow-up was extended. All patients underwent iEEG investigations (500 Hz high-pass filter and 2,000 Hz sampling rate), surgical resection, and postoperative magnetic resonance imaging (MRI). HFOs (ripples, 80–250 Hz; fast ripples, >250 Hz) were identified visually on a 5–10 min interictal iEEG sample. HFO rates inside versus outside the seizure-onset zone (SOZ), in resected versus nonresected tissue, and their association with surgical outcome (ILAE classification) were assessed in the entire cohort, and in the TLE and ETLE subgroups. We also tested the correlation of resected brain hippocampal and amygdala volumes (as measured on postoperative MRIs) with surgical outcome. Key Findings HFO rates were significantly higher inside the SOZ than outside in the entire cohort and TLE subgroup, but not in the ETLE subgroup. In all groups, HFO rates did not differ significantly between resected and nonresected tissue. Surgical outcome was better when higher HFO rates were included in the surgical resection in the entire cohort and TLE subgroup, but not in the ETLE subgroup. Resected brain hippocampal and amygdala volumes were not correlated with

  9. Diagnostic discrepancies in malignant astrocytoma due to limited surgical resection can be overcome by IDH1 testing

    PubMed Central

    Kim, Betty Y. S.; Jiang, Wen.; Beiko, Jason; Prabhu, Sujit S.; DeMonte, Franco; Gilbert, Mark R.; Sawaya, Raymond; Aldape, Kenneth D.; Cahill, Daniel P.; McCutcheon, Ian E.

    2015-01-01

    Background The accurate grading of malignant astrocytomas has significant prognostic and therapeutic implications. Traditional histopathological grading can be challenging due to regional tumor heterogeneity, especially in scenarios where small amounts of tissue are available for pathologic review. Here, we hypothesized that a critical tumor resection volume is needed for correct grading of astrocytomas by histopathology. For insufficient tissue sampling, IDH1 molecular testing can act as a complementary marker to improve diagnostic accuracy. Methods Volumetric analyses were obtained using preoperative and postoperative MRI images. Histological specimens were gathered from 403 patients with malignant astrocytoma who underwent craniotomy. IDH1 status was assessed by immunohistochemistry and sequencing. Results Patients with >20 cubic centimeters (cc) of the total tumor volume resected on MRI have higher rate of GBM diagnosis compared to <20cc (OR 2.57, 95% CI 1.6-4.06, P<0.0001). The rate of IDH1 status remained constant regardless of the tumor volume resected (OR 0.81, 95% CI 0.48-1.36, P<0.43). The rate of GBM diagnosis is 2-fold greater for individual surgical specimen >10cc than those of lower volume (OR 2.48, 95% CI 1.88-3.28, P<0.0001). Overall survival for AA patients with >20cc tumor resection on MRI is significantly better than those with <20cc tumor resected (P<0.05). No volume-dependent differences were observed in patients with GBM (P<0.4), IDH1 wild type (P<0.1) or IDH1 mutation (P<0.88). Conclusions IDH1 status should be considered when total resection volume is <20cc based on MRI analysis and for surgical specimen < 10cc to complement histopathologic diagnosis of malignant astrocytomas. In these specimens, under-diagnosis of GBM may occur when analysis is restricted to histopathology alone. PMID:24777756

  10. Palliative resection of a primary tumor in patients with unresectable colorectal cancer: could resection type improve survival?

    PubMed Central

    Jang, Hyun Seok; Kim, Chang Hyun; Lee, Soo Young; Kim, Hyeong Rok; Kim, Young Jin

    2016-01-01

    Purpose The aim of this study was to evaluate the impact of extended resection of primary tumor on survival outcome in unresectable colorectal cancer (UCRC). Methods A retrospective analysis was conducted for 190 patients undergoing palliative surgery for UCRC between 1998 and 2007 at a single institution. Variables including demographics, histopathological characteristics of tumors, surgical procedures, and course of the disease were examined. Results Kaplan-Meier survival curve indicated a significant increase in survival times in patients undergoing extended resection of the primary tumor (P < 0.001). Multivariate analysis showed that extra-abdominal metastasis (P = 0.03), minimal resection of the primary tumor (P = 0.034), and the absence of multimodality adjuvant therapy (P < 0.001) were significantly associated poor survival outcome. The histological characteristics were significantly associated with survival times. Patients with well to moderate differentiation tumors that were extensively resected had significantly increased survival time (P < 0.001), while those with poor differentiation tumors that were extensively resected did not have increase survival time (P = 0.786). Conclusion Extended resection of primary tumors significantly improved overall survival compared to minimal resection, especially in well to moderately differentiated tumors (survival time: extended resection, 27.8 ± 2.80 months; minimal resection, 16.5 ± 2.19 months; P = 0.002). PMID:27757394

  11. The method of intraoperative analysis of structural and metabolic changes in the area of tumor resection

    NASA Astrophysics Data System (ADS)

    Savelieva, Tatiana A.; Loshchenov, Victor B.; Volkov, Vladimir V.; Linkov, Kirill G.; Goryainov, Sergey A.; Potapov, Alexander A.

    2014-05-01

    The method of intraoperative analysis of tumor markers such as structural changes, concentrations of 5- ALA induced protoporphyrin IX and hemoglobin in the area of tissue resection was developed. A device for performing this method is a neurosurgical aspiration cannulae coupled with the fiber optic probe. The configuration of fibers at the end of cannulae was developed according to the results of numerical modeling of light distribution in biological tissues. The optimal distance between the illuminating and receiving fiber was found for biologically relevant interval of optical properties. On this particular distance the detected diffuse reflectance depends on scattering coefficient almost linearly. Array of optical phantoms containing hemoglobin, protoporphyrin IX and fat emulsion (as scattering media) in various concentrations was prepared to verify the method. The recovery of hemoglobin and protoporphyrin IX concentrations in the scattering media with an error less than 10% has been demonstrated. The fat emulsion concentration estimation accuracy was less than 12%. The first clinical test was carried out during glioblastoma multiforme resection in Burdenko Neurosurgery Institute and confirmed that sensitivity of this method is enough to detect investigated tumor markers in vivo. This method will allow intraoperative analysis of the structural and metabolical tumor markers directly in the zone of destruction of tumor tissue, thereby increasing the degree of radical removal and preservation of healthy tissue.

  12. [Bioelectrical activity and evacuation function of the gastric stump in an early period after different means of gastric resection and variations in the formation of anastomoses].

    PubMed

    Kapustin, B B; Khalimov, E V

    2003-01-01

    The results of the stomach resection on the occasion of stomach and duodenal ulcer were analyzed. Bioelectric activity of the stomach stump was studied in a comparative aspect, and early recovery of the motor function of the resected stomach after the formation of pyloroimitating gastroduodenal anastomoses was shown. Revealed roentgenologic mechanisms of the evacuator function of the stomach stump let us determine evacuation types for the early postoperative period. The formation of pyloroimitating gastroduodenal anastomoses is functionally advantageous.

  13. Fortune of temporary ileostomies in patients treated with laparoscopic low anterior resection for rectal cancer

    PubMed Central

    Haksal, Mustafa; Okkabaz, Nuri; Atici, Ali Emre; Civil, Osman; Ozdenkaya, Yasar; Erdemir, Ayhan; Aksakal, Nihat

    2017-01-01

    Purpose The current study aims to analyze the risk factors for the failure of ileostomy reversal after laparoscopic low anterior resection for rectal cancer. Methods All patients who underwent a laparoscopic low anterior resection for rectal cancer with a diverting ileostomy between 2007 and 2014 were abstracted. The patients who underwent and did not undergo a diverting ileostomy procedure were compared regarding patient, tumor, treatment related parameters, and survival. Results Among 160 (103 males [64.4%], mean [± standard deviation] age was 58.1 ± 11.9 years) patients, stoma reversal was achieved in 136 cases (85%). Anastomotic stricture (n = 13, 52.4%) was the most common reason for stoma reversal. These were the risk factors for the failure of stoma reversal: Male sex (P = 0.035), having complications (P = 0.01), particularly an anastomotic leak (P < 0.001), or surgical site infection (P = 0.019) especially evisceration (P = 0.011), requirement for reoperation (P = 0.003) and longer hospital stay (P = 0.004). Multivariate analysis revealed that male sex (odds ratio [OR], 7.82; P = 0.022) and additional organ resection (OR, 6.71; P = 0.027) were the risk factors. Five-year survival rates were similar (P = 0.143). Conclusion Fifteen percent of patients cannot receive a stoma reversal after laparoscopic low anterior resection for rectal cancer. Anastomotic stricture is the most common reason for the failure of stoma takedown. Having complications, particularly an anastomotic leak and the necessity of reoperation, limits the stoma closure rate. Male sex and additional organ resection are the risk factors for the failure in multivariate analyses. These patients require a longer hospitalization period, but have similar survival rates as those who receive stoma closure procedure. PMID:28090504

  14. Transurethral resection of the ejaculatory duct.

    PubMed

    Paick, J S

    2000-05-01

    Complete bilateral ejaculatory duct obstruction has long been recognized as an uncommon, treatable form of male infertility. Partial ejaculatory duct obstruction reflects a disturbance of ejaculation where sperm quality is impaired during transit through the distal vas deferens and ejaculatory ducts. With the advent and increased use of high-resolution transrectal ultrasonography, abnormalities of the distal ejaculatory ducts related to infertility have been well documented. Although there are no pathognomonic findings associated with ejaculatory duct obstruction, several clinical findings are highly suggestive. In an infertile man with oligospermia or azoospermia with low ejaculate volume, normal secondary sexual characteristics, testes and hormonal profile and dilated seminal vesicles, midline cyst, or calcification on transrectal ultrasonography, ejaculatory duct obstruction is suggested. Of course, other causes of infertility may be concomitantly present and need to be searched for and treated as well. In selected cases, transurethral resection has resulted in marked improvement in semen parameters and pregnancies have been achieved. As is the case with all surgical procedures, proper patient selection and surgical experience are necessary to obtain optimal results. However, it appears that the treatments currently available for relief of ejaculatory obstruction are not optimally effective. Only approximately one half of treated patients will have an improvement in semen parameters and only about one quarter of treated patients will contribute to a pregnancy. What remains to be determined is how to manage the additional nearly 50% of patients who do not benefit from transurethral resection of ejaculatory obstruction. Based on my experience, I suggest that transrectal ultrasonography should be the first diagnostic procedure used when infertile men are suspected of having ejaculatory duct obstruction; however, vasography should still be considered for a more

  15. Resection of sternal metastasis from endometrial carcinoma followed by reconstruction with sandwiched marlex and stainless steel mesh: report of a case.

    PubMed

    Haraguchi, Shuji; Hioki, Masafumi; Hisayoshi, Takao; Yamashita, Koji; Koizumi, Kiyoshi; Shimizu, Kazuo

    2006-01-01

    We report the successful resection of sternal metastasis from endometrial carcinoma, followed by reconstruction of the chest defect, in an 87-year-old woman. We performed subtotal sternectomy and concurrent resection of the ribs and overlying soft tissue. The skeletal defect was then reconstructed with sandwiched Marlex and stainless steel mesh, and soft tissue coverage was accomplished by using a pectoralis major advancement flap. The patient had an uneventful postoperative course with no sign of recurrence during 5 years of follow-up. Thus, reconstruction with Marlex and stainless steel mesh could be an effective technique for preventing paradoxical movement of the thorax and protecting the intrathoracic organs.

  16. Robotic resection of an ectopic goiter in the mediastinum.

    PubMed

    Bodner, Johannes; Fish, John; Lottersberger, Andreas C; Wetscher, Gerold; Schmid, Thomas

    2005-08-01

    We report the first robotic resection of an ectopic mediastinal thyroid adenoma in a 72-year-old woman. This intervention was part of staged management for excessive bilateral cervical goiter with intrathoracic dispersion. The robotic resection was found to be feasible and safe. The robotic operating system offers better visual control and operative accuracy than does conventional thoracoscopy.

  17. Single incision glove port laparoscopic colorectal cancer resection

    PubMed Central

    Joshi, HMN; Gosselink, MP; Adusumilli, S; Hompes, R; Cunningham, C; Lindsey, I

    2015-01-01

    Introduction The advantages of single port surgery remain controversial. This study was designed to evaluate the safety and feasibility of single incision glove port colon resections using a diathermy hook, reusable ports and standard laparoscopic straight instrumentation. Methods Between June 2012 and February 2014, 70 consecutive patients (30 women) underwent a colonic resection using a wound retractor and glove port. Forty patients underwent a right hemicolectomy through the umbilicus and thirty underwent attempted single port resection via an incision in the right rectus sheath (14 high anterior resection, 13 low anterior resection, 3 abdominoperineal resection). Results Sixty-two procedures (89%) were completed without conversion to open or multiport techniques. Four procedures had to be converted and additional ports were needed in four other patients. The postoperative mortality rate was 0%. Complications occurred in six patients (9%). Two cases were R1 while the remainder were R0 with a median nodal harvest of 20 (range: 9–48). The median length of hospital stay was 5 days (range: 3–25 days) (right hemicolectomy: 5 days (range: 3–12 days), left sided resection: 6 days (range: 4–25 days). At a median follow-up of 14 months, no port site hernias were observed. Conclusions Single incision glove port surgery is an appropriate technique for different colorectal cancer resections and has the advantage of being less expensive than surgery with commercial single incision ports. PMID:26263805

  18. Downstaging Hepatocellular Carcinoma with Yttrium-90 radioembolization: resection or transplantation?

    PubMed

    Ettorre, G M; Laurenzi, A; Vennarecci, G

    2014-06-01

    Trans Arterial Radio Embolization with Yttrium 90 in the treatment of Hepatocellular Carcinoma is becoming a new interesting tool in the treatment of patients that are considered non resectable and non transplantable. A successful downstaging could improve the number of patients that could benefit from a resection or a liver transplantation, but some points still need to be addressed.

  19. The EndoRotor®: endoscopic mucosal resection system for non-thermal and rapid removal of esophageal, gastric, and colonic lesions: initial experience in live animals

    PubMed Central

    Hollerbach, Stephan; Wellmann, Axel; Meier, Peter; Ryan, Jeffery; Franco, Ramon; Koehler, Peter

    2016-01-01

    Background and study aims: The EndoRotor® is a novel, non-thermal, automated mechanical endoscopic resection system designed to remove benign mucosal neoplastic tissue throughout the gastrointestinal tract. It uses suction pressure to pull in mucosa and rapidly and precisely cut it while automatically transporting the samples to a collection trap for later histologic evaluation. Patients and methods: To study the technical properties and therapeutic potential of this new tool, we performed multiple upper and lower gastrointestinal endoscopic mucosal resections in three healthy live pigs. Animals were anesthetized and kept artificially ventilated while two physicians performed multiple qualitative mucosal resections on various sites of the pigs’ esophagus, stomach, duodenum, and colon. Results: Rapid resection of flat and slightly elevated mucosa up to several centimeters in size/diameter was performed. No major bleeding occurred during and after resections. When used properly, no gastrointestinal wall perforations occurred during superficial resections. Perforations in the colon were only observed when the device was deliberately pushed against deeper sub-mucosal layers or when exceptional force was applied to penetrate the gastrointestinal wall. Histologic specimens showed complete mucosal removal at resection sites. The flexible catheter could be moved and directed towards most of the areas of interest in the gastrointestinal tract. Conclusion: The EndoRotor rapidly and easily resects flat and slightly elevated gastrointestinal mucosa with a short learning curve. Future studies in humans should be performed to prove its ability for large-area mucosal resections in benign conditions such as laterally spreading adenomas in the colon, or Barrett’s mucosa in the distal esophagus. PMID:27092332

  20. Endoscopic Resection of Gastric Submucosal Tumors: A Comparison of Endoscopic Nontunneling with Tunneling Resection and a Systematic Review

    PubMed Central

    Zhang, Qiang; Wang, Fei; Wei, Gong; Cai, Jian-Qun; Zhi, Fa-Chao; Bai, Yang

    2017-01-01

    Background/Aim: Endoscopic tunneling resection is a relatively novel endoscopic technology for removing gastric submucosal tumors. Our study aimed to compare the differences between tunneling and nontunneling resection for gastric submucosal tumors. Materials and Methods: Resections of gastric submucosal tumors (n = 97) performed from 2010 to 2015 at our endoscopy center were reviewed, and PubMed was searched for clinical studies on gastric submucosal tumor resection by endoscopic nontunneling and tunneling techniques. Results: At our endoscopy center, nontunneling (Group 1) and tunneling resection (Group 2) were performed for 78 and 19 submucosal tumors, respectively; median tumor diameters were 15 and 20 mm (P = 0.086), median procedural times were 50 and 75 min (P = 0.017), successful resection rates were 94.9% (74/78) and 89.5% (17/19) (P = 0.334), and en bloc resection rates were 95.9% (71/74) and 94.1% (16/17) (P = 0.569) in the Groups 1 and 2, respectively. Postoperative fever, delayed hemorrhage and perforation, hospitalization time, and hospitalization expense were statistically similar between the 2 groups. A literature review on gastric submucosal tumor resection suggested that the en bloc resection rates of the two methods for tumors with a median diameter of 15–30 mm were also high, and there were no relapses during the follow-up period. Conclusions: Both endoscopic nontunneling and tunneling resection seem to be effective and safe methods for removing relatively small gastric submucosal tumors. Compared with endoscopic nontunneling, tunneling resection does not seem to have distinct advantages for gastric submucosal tumors, and has a longer mean operative time. PMID:28139501

  1. Cephalic aura after frontal lobe resection.

    PubMed

    Kakisaka, Yosuke; Jehi, Lara; Alkawadri, Rafeed; Wang, Zhong I; Enatsu, Rei; Mosher, John C; Dubarry, Anne-Sophie; Alexopoulos, Andreas V; Burgess, Richard C

    2014-08-01

    A cephalic aura is a common sensory aura typically seen in frontal lobe epilepsy. The generation mechanism of cephalic aura is not fully understood. It is hypothesized that to generate a cephalic aura extensive cortical areas need to be excited. We report a patient who started to have cephalic aura after right frontal lobe resection. Magnetoencephalography (MEG) showed interictal spike and ictal change during cephalic aura, both of which were distributed in the right frontal region, and the latter involved much more widespread areas than the former on MEG sensors. The peculiar seizure onset pattern may indicate that surgical modification of the epileptic network was related to the appearance of cephalic aura. We hypothesize that generation of cephalic aura may be associated with more extensive cortical involvement of epileptic activity than that of interictal activity, in at least a subset of cases.

  2. [Short bowel: from resection to transplantation].

    PubMed

    Rodríguez-Montes, José Antonio

    2014-09-17

    Short bowel syndrome (SBS) is characterized by a significant reduction in the effective intestinal surface by an anatomical or functional loss of the small intestine. It mainly occurs after extensive bowel resection, intestinal intrinsic disease or surgical bypass. The main complications are malabsorption, maldigestion, malnutrition, dehydratation and, potentially, lethal metabolic lesions. The treatment is based on appropiate, individualized nutritional support; however, the most recent outcomes on bowel transplantation (BT) and a great rate of survivors achieving complete digestive autonomy and able to carry out activities according to their age allow for considering BT as the first choice therapy in patients with irreversible intestinal failure in whom poor prognosis with parenteral nutrition is foreseen. In this paper the most outstanding aspects of SBS are revised.

  3. [Perioperative stroke following transurethral resection of prostate: high index of suspicion and stabilization of physiological parameters can save lives].

    PubMed

    Nag, Deb Sanjay; Chatterjee, Abhishek; Samaddar, Devi Prasad; Agarwal, Ajay

    2017-01-09

    We report a case of a 72 year old hypertensive male who developed severe hypertension followed by neurological deterioration in the immediate postoperative period after transurethral resection of prostate. While arterial blood gas and laboratory tests excluded transurethral resection of prostate syndrome or any other metabolic cause, reduction of blood pressure failed to ameliorate the symptoms. A cranial CT done 4hours after the onset of neurological symptoms revealed bilateral gangliocapsular and right thalamic infarcts. Oral aspirin was advised to prevent early recurrent stroke. Supportive treatment and mechanical ventilation ensured physiological stability and the patient recovered completely over the next few days without any residual neurological deficit.

  4. A Case Report of Onyx Pulmonary Arterial Embolism Contributing to Hypoxemia During Awake Craniotomy for Arteriovenous Malformation Resection.

    PubMed

    Tolly, Brian T; Kosky, Jenna L; Koht, Antoun; Hemmer, Laura B

    2017-02-15

    A healthy 26-year-old man with cerebral arteriovenous malformation underwent staged endovascular embolization with Onyx followed by awake craniotomy for resection. The perioperative course was complicated by tachycardia and severe intraoperative hypoxemia requiring significant oxygen supplementation. Postoperative chest computed tomography (CT) revealed hyperattenuating Onyx embolization material within the pulmonary vasculature, and an electrocardiogram indicated possible right heart strain, supporting clinically significant embolism. With awake arteriovenous malformation resection following adjunctive Onyx embolization becoming increasingly employed for lesions involving the eloquent cortex, anesthesiologists need to be aware of pulmonary migration of Onyx material as a potential contributor to significant perioperative hypoxemia.

  5. A Case Report of Onyx Pulmonary Arterial Embolism Contributing to Hypoxemia During Awake Craniotomy for Arteriovenous Malformation Resection.

    PubMed

    Tolly, Brian T; Kosky, Jenna L; Koht, Antoun; Hemmer, Laura B

    2016-11-02

    A healthy 26-year-old man with cerebral arteriovenous malformation underwent staged endovascular embolization with Onyx followed by awake craniotomy for resection. The perioperative course was complicated by tachycardia and severe intraoperative hypoxemia requiring significant oxygen supplementation. Postoperative chest computed tomography (CT) revealed hyperattenuating Onyx embolization material within the pulmonary vasculature, and an electrocardiogram indicated possible right heart strain, supporting clinically significant embolism. With awake arteriovenous malformation resection following adjunctive Onyx embolization becoming increasingly employed for lesions involving the eloquent cortex, anesthesiologists need to be aware of pulmonary migration of Onyx material as a potential contributor to significant perioperative hypoxemia.

  6. The effects of scalpel, harmonic scalpel and monopolar electrocautery on the healing of colonic anastomosis after colonic resection

    PubMed Central

    Pekcici, M. Recep; Altunkaya, Canan; Fidanci, Vildan; Kilinc, Aytul; Ozer, Huseyin; Tekeli, Ahmet; Aydinuraz, Kuzey; Guler, Osman

    2016-01-01

    Purpose In our study, the effects of harmonic scalpel, scalpel, and monopolar electrocautery usage on the health and healing of colon anastomosis after resection was investigated. Methods In this study, 120 female albino Wistar rats were divided into 3 groups each containing 40 rats. Group A, resection with scalpel; group B, resection with monopolar electrocautery; group C, resection with harmonic scalpel. The groups were divided into 4 subgroups consisting of 10 rats and analysed in the postoperative 1st, 3rd, 5th, and 7th days. Anastomotic bursting pressures, hydroxyproline levels and histopathological parameters were surrogate parameters for evaluating wound healing. Results The tissue hydroxyproline levels did not show any significant difference between the groups and subgroups. The mean bursting pressure of group A on the 5th day was significantly higher than groups B and C (P < 0.001). When the fibroblast and fibrosis scores were evaluated, scores of group C on the 5th day were significantly higher than the other groups, but the results of bursting pressures and biochemical parameters did not support the fibroblast and fibrosis scores. There were not any significant differences between the groups in other histopathologic parameters. Conclusion The use of monopolar electrocautery needs more attention since the device causes tissue destruction. The obliterating effect of harmonic scalpel on luminal organs is an important problem, especially if an anastomosis is planned. Despite the disadvantages of scalpel, its efficacy on early wound healing is better than the other devices. PMID:27274507

  7. Selection and Outcome of Portal Vein Resection in Pancreatic Cancer

    PubMed Central

    Nakao, Akimasa

    2010-01-01

    Pancreatic cancer has the worst prognosis of all gastrointestinal neoplasms. Five-year survival of pancreatic cancer after pancreatectomy is very low, and surgical resection is the only option to cure this dismal disease. The standard surgical procedure is pancreatoduodenectomy (PD) for pancreatic head cancer. The morbidity and especially the mortality of PD have been greatly reduced. Portal vein resection in pancreatic cancer surgery is one attempt to increase resectability and radicality, and the procedure has become safe to perform. Clinicohistopathological studies have shown that the most important indication for portal vein resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, portal vein resection is contraindicated. PMID:24281213

  8. [Prevention of gastrostasis after pancreaticoduodenal resection: new technique of gastroenterostomy].

    PubMed

    Skipenko, O G; Bedzhanian, A L; Shatverian, G A; Bagmet, N N; Chardarov, N K

    2015-01-01

    It was performed a retrospective comparative analysis of treatment results of 113 patients with pancreatic head and periampular cancer. The main group consisted of 58 patients in whom pancreaticoduodenal resection was performed according to an original technique of Russian Scientific Center of Surgery. Control group included 55 patients who underwent end-to-side gastrojejunostomy reconstruction. We have analyzed immediate postoperative complications in 2 groups without taking into consideration nosological forms of the disease. Pancreaticojejunostomy failure was diagnosed postoperatively in 5 (8.6%) patients in main group and in 10 (18.2%) patients in control group. There was no hepaticoentero- and gastroenterostomy failure in patients who underwent new technique of gastrojejunostomy while these events were observed in 8 (14.5%) and 3 (5.5%) patients respectively in control group. Mortality was 1.7% (n=1) in main group and 5.5% (n=3) in control group (p=0.29). Mild degree of gastrostasis (A class) was observed in 54 (93.7%) patients of main group and in 34 (61.8%) patients of control group (p=0.0004). There was B class of gastrostasis in 4 (6.9%) patients of main group. Severe gastrostasis (C class) was not revealed in any observation. In control group B class of gastrostasis was diagnosed in 14 (25.5%) patients, severe degree - in 7 (12.7%) patients. Univariant analysis showed hemotransfusion (p=0.037), pancreatic fistula (p=0.001), enteric fistula (p=0.005) and reconstruction technique (p=0.00004) as predictors of gastrostasis. Multivariant analysis defined pancreatic fistula (p=0.01), enteric fistula (p=0.04) and reconstruction technique (p=0.001) as significant predictors of gastrostasis. Thus, our study revealed significant decreasing gastrostasis incidence in case of original technique in comparison with conventional anastomosis, as well as demonstrated effect of anastomoses failure on augmentation of gastrostasis frequency after pancreaticoduodenal resection

  9. [A