Outcomes of patients with abdominoperineal resection (APR) and low anterior resection (LAR) who had very low rectal cancer.

PubMed

Yeom, Seung-Seop; Park, In Ja; Jung, Sung Woo; Oh, Se Heon; Lee, Jong Lyul; Yoon, Yong Sik; Kim, Chan Wook; Lim, Seok-Byung; Kim, Nayoung; Yu, Chang Sik; Kim, Jin Cheon

2017-10-01

We compared the oncological outcomes of sphincter-saving resection (SSR) and abdominoperineal resection (APR) in 409 consecutive patients with very low rectal cancer (i.e., tumors within 3 cm from the anal verge); 335 (81.9%) patients underwent APR and 74 (18.1%) underwent SSR. The APR group comprised higher proportions of men (67.5% vs 55.4%, P = .049) and advanced-stage patients (P < .001). Preoperative chemoradiotherapy (PCRT) was more frequently administered in the SSR group (83.8% vs 52.8%, P < .001). Overall, the systemic and local recurrence rates were 29.1% and 6.1%, respectively. On stratification according to PCRT and pathologic stage, the mode of surgery did not affect the recurrence type. Moreover, recurrence-free survival (RFS) did not differ according to the mode of surgery in different cancer stages. RFS was associated with ypT and ypN stages in patients who received PCRT, while pN stage, lymphovascular invasion (LVI), and circumferential resection margin (CRM) involvement were risk factors for RFS in those who did not receive PCRT. Notably, SSR was not found to be a risk factor for RFS in either subgroup. Patients who were stratified according to cancer stage and PCRT also showed no differences in RFS according to the mode of surgery. Our results demonstrate that, regardless of PCRT administration, SSR is an effective treatment for very low rectal cancer, while CRM is an important prognostic factor for patients who did not receive PCRT.

Multicentre propensity score-matched analysis of conventional versus extended abdominoperineal excision for low rectal cancer.

PubMed

Ortiz, H; Ciga, M A; Armendariz, P; Kreisler, E; Codina-Cazador, A; Gomez-Barbadillo, J; Garcia-Granero, E; Roig, J V; Biondo, S

2014-06-01

Abdominal perineal excision (APE) was originally described with levator ani removal for rectal cancer. An even wider, more aggressive extralevator resection for APE has been proposed. Although some surgeons are performing a very wide 'extralevator APE (ELAPE)', there are few data to recommend it routinely. This multicentre study aimed to compare outcomes of APE and ELAPE. A multicentre propensity case-matched analysis comparing two surgical approaches (APE and ELAPE) was performed. All patients who underwent abdominoperineal resection of a rectal tumour were considered for the analysis. Tumour height was defined by magnetic resonance imaging measurement and patients with stage II-III tumours had neoadjuvant radiochemotherapy. Involvement of the circumferential resection margin (CRM) and intraoperative tumour perforation were the main outcome measures. A logistic regression model was used to study the relationship between the surgical approaches and outcomes. From January 2008 to March 2013 a total of 1909 consecutive patients underwent APE or ELAPE, of whom 914 matched patients (457 in each group) formed the cohort for analysis. Intraoperative tumour perforation occurred in 7.9 and 7.7 per cent of patients during APE and ELAPE respectively (P = 0.902), and there was CRM involvement in 13.1 and 13.6 per cent (P = 0.846). There were no differences between APE and ELAPE in terms of postoperative complication rates (52.3 versus 48.1 per cent; P = 0.209), need for reoperation (7.7 versus 7.0 per cent; P = 0.703), perineal wound problems (26.0 versus 21.9 per cent; P = 0.141), mortality rate (2.0 versus 2.0 per cent; P = 1.000) and local recurrence rate at 2 years (2.7 versus 5.6 per cent; P = 0.664). ELAPE does not improve rates of CRM involvement, intraoperative tumour perforation, local recurrence or mortality. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

The Need for Consensus and Transparency in Assessing Population-Based Rates of Positive Circumferential Radial Margins in Rectal Cancer: Data from Consecutive Cases in a Large Region of Ontario, Canada.

PubMed

Keng, Christine; Coates, Angela; Grubac, Vanja; Lovrics, Peter; DeNardi, Franco; Thabane, Lehana; Simunovic, Marko

2016-02-01

A positive circumferential radial margin (CRM) after rectal cancer surgery is an important predictor of local recurrence. The definition of a positive CRM differs internationally, and reported rates vary greatly in the literature. This study used time-series population-based data to assess positive CRM rates in a region over time and to inform future methods of CRM analysis in a defined geographic area. Chart reviews provided relevant data from consecutive patients undergoing rectal cancer surgery between 2006 and 2012 in all hospitals of the authors' region. Outcomes included rates for pathologic examination of CRM, CRM distance reporting, and positive CRM. The rate of positive CRM was calculated using various definitions. The variations included positive margin cutoffs of CRM at 1 mm or less versus 2 mm or less and inclusion or exclusion of cases without CRM assessment. In this study, 1222 consecutive rectal cancer cases were analyzed. The rate for pathology reporting of CRM distance increased from 54.7 to 93.2 % during the study. Depending on how the rate of positive CRM was defined, its value varied 8.5 to 19.4 % in 2006 and 6.0 to 12.5 % in 2012. Using a pre-specified definition, the rate of positive CRM decreased over time from 14.0 to 6.3 %. A marked increase in CRM distance reporting was observed, whereas the rates of positive CRM dropped, suggesting improved pathologist and surgeon performance over time. Changing definitions greatly influenced the rates of positive CRM, indicating the need for more transparency when such population-based rates are reported in the literature.

Effect of Robotic-Assisted vs Conventional Laparoscopic Surgery on Risk of Conversion to Open Laparotomy Among Patients Undergoing Resection for Rectal Cancer

PubMed Central

Pigazzi, Alessio; Marshall, Helen; Croft, Julie; Corrigan, Neil; Copeland, Joanne; Quirke, Phil; West, Nick; Rautio, Tero; Thomassen, Niels; Tilney, Henry; Gudgeon, Mark; Bianchi, Paolo Pietro; Edlin, Richard; Hulme, Claire; Brown, Julia

2017-01-01

Importance Robotic rectal cancer surgery is gaining popularity, but limited data are available regarding safety and efficacy. Objective To compare robotic-assisted vs conventional laparoscopic surgery for risk of conversion to open laparotomy among patients undergoing resection for rectal cancer. Design, Setting, and Participants Randomized clinical trial comparing robotic-assisted vs conventional laparoscopic surgery among 471 patients with rectal adenocarcinoma suitable for curative resection conducted at 29 sites across 10 countries, including 40 surgeons. Recruitment of patients was from January 7, 2011, to September 30, 2014, follow-up was conducted at 30 days and 6 months, and final follow-up was on June 16, 2015. Interventions Patients were randomized to robotic-assisted (n = 237) or conventional (n = 234) laparoscopic rectal cancer resection, performed by either high (upper rectum) or low (total rectum) anterior resection or abdominoperineal resection (rectum and perineum). Main Outcomes and Measures The primary outcome was conversion to open laparotomy. Secondary end points included intraoperative and postoperative complications, circumferential resection margin positivity (CRM+) and other pathological outcomes, quality of life (36-Item Short Form Survey and 20-item Multidimensional Fatigue Inventory), bladder and sexual dysfunction (International Prostate Symptom Score, International Index of Erectile Function, and Female Sexual Function Index), and oncological outcomes. Results Among 471 randomized patients (mean [SD] age, 64.9 [11.0] years; 320 [67.9%] men), 466 (98.9%) completed the study. The overall rate of conversion to open laparotomy was 10.1%: 19 of 236 patients (8.1%) in the robotic-assisted laparoscopic group and 28 of 230 patients (12.2%) in the conventional laparoscopic group (unadjusted risk difference = 4.1% [95% CI, −1.4% to 9.6%]; adjusted odds ratio = 0.61 [95% CI, 0.31 to 1.21]; P = .16). The overall CRM+ rate was 5.7%; CRM+ occurred in 14 (6.3%) of 224 patients in the conventional laparoscopic group and 12 (5.1%) of 235 patients in the robotic-assisted laparoscopic group (unadjusted risk difference = 1.1% [95% CI, −3.1% to 5.4%]; adjusted odds ratio = 0.78 [95% CI, 0.35 to 1.76]; P = .56). Of the other 8 reported prespecified secondary end points, including intraoperative complications, postoperative complications, plane of surgery, 30-day mortality, bladder dysfunction, and sexual dysfunction, none showed a statistically significant difference between groups. Results Among 471 randomized patients (mean [SD] age, 64.9 [11.0] years; 320 [67.9%] men), 466 (98.9%) completed the study. The overall rate of conversion to open laparotomy was 10.1%. The overall CRM+ rate was 5.7%. Of the other 8 reported prespecified secondary end points, including intraoperative complications, postoperative complications, plane of surgery, 30-day mortality, bladder dysfunction, and sexual dysfunction, none showed a statistically significant difference between groups. End Point No. With Outcome/Total No. (%) Unadjusted Risk Difference (95% CI), % Adjusted Odds Ratio (95% CI) P Value Conventional Laparoscopy Robotic-Assisted Laparoscopy Conversion to open laparotomy 28/230 (12.2) 19/236 (8.1) 4.1 (−1.4 to 9.6) 0.61 (0.31-1.21) .16 CRM+ 14/224 (6.3) 12/235 (5.1) 1.1 (−3.1 to 5.4) 0.78 (0.35-1.76) .56 Conclusions and Relevance Among patients with rectal adenocarcinoma suitable for curative resection, robotic-assisted laparoscopic surgery, as compared with conventional laparoscopic surgery, did not significantly reduce the risk of conversion to open laparotomy. These findings suggest that robotic-assisted laparoscopic surgery, when performed by surgeons with varying experience with robotic surgery, does not confer an advantage in rectal cancer resection. Trial Registration isrctn.org Identifier: ISRCTN80500123 PMID:29067426

MRI in T staging of rectal cancer: How effective is it?

PubMed Central

Mulla, MG; Deb, R; Singh, R

2010-01-01

Background: Rectal cancer constitutes about one-third of all gastrointestinal (GI) tract tumors. Because of the high recurrence rates (30%) in rectal cancer, it is vitally important to accurately stage these tumours preoperatively so that appropriate surgical resection can be undertaken. MRI is the ideal technique for the preoperative staging of these tumours. Aim: To determine the accuracy of local T staging of rectal cancer with MRI, using histopathological staging as the gold. Materials and Methods: Forty consecutive patients admitted with rectal cancer over a period of 18 months were included in this retrospective study. MRI scans were performed prior to surgery in all patients, on 1.5T scanners. Two radiologists, with a special interest in gastrointestinal imaging reported all images. Two dedicated histopathologists reported the histology slides. The accuracy of preoperative local MRI T staging was assessed by comparison with postoperative histopathological staging. Results: There was agreement between MRI and histopathology (TNM) staging in 12 patients (30%). The sensitivity and specificity of MRI for T staging was 89% and 67% respectively. The circumferential resection margin (CRM) status was accurately staged in 94.1% of the patients. Conclusions: Preoperative staging with MRI is sensitive in identifying CRM involvement, which is the main factor affecting the outcome of surgery. PMID:20607023

Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.

PubMed

Patel, Uday B; Taylor, Fiona; Blomqvist, Lennart; George, Christopher; Evans, Hywel; Tekkis, Paris; Quirke, Philip; Sebag-Montefiore, David; Moran, Brendan; Heald, Richard; Guthrie, Ashley; Bees, Nicola; Swift, Ian; Pennert, Kjell; Brown, Gina

2011-10-01

To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

A pilot randomized study comparing extralevator with conventional abdominoperineal excision for low rectal cancer after neoadjuvant chemoradiation.

PubMed

Seshadri, R A; West, N P; Sundersingh, S

2017-07-01

The aims of this study were to assess the feasibility of performing an extralevator abdominoperineal excision (ELAPE) after neoadjuvant chemoradiation (NCRT), to compare the rates of circumferential resection margin (CRM) involvement and intra-operative perforation (IOP) of the specimen, and to assess the amount of tissue removed around the muscularis propria (MP)/internal sphincter (IS) of the lower rectum in patients with low rectal cancer undergoing ELAPE compared with conventional abdominoperineal excision (CAPE) after NCRT. This was an open-label, parallel-arm pilot randomized trial conducted in India. Twenty patients were randomized to one of the study arms. The surgical specimens were fixed, serially cross-sectioned and photographed. Using specialized morphometry software, the amount of tissue resected with each operation was measured. There was a nonsignificant trend towards more IOPs (30% vs 0%, P = 0.06) and a higher CRM involvement rate (40% vs 20%, P = 0.32) in the CAPE arm. ELAPE removed a significantly greater amount of tissue around the IS/MP when compared with CAPE (mean ± SD: 1911.39 ± 382 mm 2 vs 1132.03 ± 371 mm 2 , P < 0.001). The mean distance from the IS/MP to the CRM was significantly greater in the ELAPE arm both in the posterior (mean ± SD: 28.28 ± 3 mm vs 9.63 ± 3 mm, P < 0.001) and lateral (mean ± SD: 13.69 ± 3 mm vs 9.72 ± 3 mm, P = 0.009) parts of the rectum but not in the anterior part (mean ± SD: 6.74 ± 2 mm vs 6.10 ± 4 mm, P = 0.64). The short-term morbidity was not significantly different between the two procedures. ELAPE removed more tissue in the lower rectum and resulted in a lower rate of IOP and CRM involvement when compared with CAPE, even after NCRT. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

Prognostic role of initial pan-endoscopic tumor length at diagnosis in operable esophageal squamous cell carcinoma undergoing esophagectomy with or without neoadjuvant concurrent chemoradiotherapy

PubMed Central

Lin, Chen-Sung; Liu, Chao-Yu; Cheng, Chih-Tao; Tsai, Yu-Chen; Chiou, Lun-Wei; Lee, Ming-Yuan

2017-01-01

Background The objective of this study was to appraise the prognostic role of initial pan-endoscopic tumor length at diagnosis within or between operable esophageal squamous cell carcinoma (ESCC) undergoing upfront esophagectomy or neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by esophagectomy. Methods Between Jan 2001 and Dec 2013 in Koo-Foundation Sun Yat-sen Cancer Center in Taiwan, 101 ESCC patients who underwent upfront esophagectomy (surgery group) and 128 nCCRT followed by esophagectomy (nCCRT-surgery group) were retrospectively collected. Prognostic variables, including initial pan-endoscopic tumor length at diagnosis (sub-grouped ≤3, 3–5 and >5 cm), status of circumferential resection margin (CRM), and pathological T/N/M-status and cancer stage, were appraised within or between surgery and nCCRT-surgery groups. Results Within surgery group, longer initial pan-endoscopic tumor length at diagnosis (≤3, 3–5 and >5 cm; HR =1.000, 1.688 and 4.165; P=0.007) was an independent prognostic factor that correlated with advanced T/N/M-status, late cancer stage, and CRM invasion (all’s P<0.001). Based on the initial pan-endoscopic tumor length at diagnosis ≤3, 3–5 and >5 cm, nCCRT-surgery group had a poorer (P=0.039), similar (P=0.447) and better (P<0.001) survivals than did surgery group, respectively. For those with initial pan-endoscopic tumor length at diagnosis >5 cm, nCCRT-surgery group had more percentage of T0/N0-status and stage 0 (all’s P<0.05), and fewer rate of CRM invasion (P=0.036) than did surgery group. Conclusions Initial pan-endoscopic tumor length at diagnosis could be a criterion to select proper ESCC cases for nCCRT followed by esophagectomy to improve survival and reduce CRM invasion. PMID:29221296

Transoral bisected resection for T1-2 oral tongue squamous cell carcinoma to secure adequate deep margin.

PubMed

Choi, Nayeon; Cho, Jae-Keun; Lee, Eun Kyu; Won, Sung Jun; Kim, Bo Young; Baek, Chung-Hwan

2017-10-01

To investigate the clinical usefulness of transoral bisected resection (TBR) asa new method to secure adequate deep resection margin in T1-2 oral tongue squamous cell carcinomas (SCC). Among 75 patients with cT1-2N0 oral tongue SCCs, 45 (60%) received transoral en-bloc resection (TER) while 30 (40%) received patients underwent TBR. Primary tumor resection was performed with 1.5-cm surgical resection margin for both groups. Mucosal and deep resection margins, adjuvant treatments including re-resection of the tongue and cheomoradiotherapy, local and regional recurrence free survival, and overall survival were compared between the two groups. Mean deep resection margin in the TBR group was 9.9mm (95% CI: 8.4-11.4mm), which was significantly (P<0.001) wider than that of the TER group (mean: 5.4mm, 95% CI: 4.5-6.3mm). However, mucosal resection margins were not significantly (P=0.153) different between the two groups. Re-resection of tongue was performed for 6 (13.3%) of 17 (37.8%) patients with inadequate deep resection margin in the TER group and none (0%) in 4 (13.3%) patients with inadequate deep resection margin in the TBR group. Adjuvant radiation due to inadequate deep resection margin was performed for 6.7% of patients in both groups. The TBR group had better local recurrence free survival than the TER group. However, regional recurrence free survival and overall survival were not significantly different between the two groups. TBR could provide adequate deep resection margin for early stage tongue cancers with better local tumor control than TER. It can decrease the necessity of adjuvant treatment for re-resection of the tongue. Copyright © 2017 Elsevier Ltd. All rights reserved.

One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach.

PubMed

Hamady, Zaed Z R; Lodge, J Peter A; Welsh, Fenella K; Toogood, Giles J; White, Alan; John, Timothy; Rees, Myrddin

2014-03-01

To investigate the influence of clear surgical resection margin width on disease recurrence rate after intentionally curative resection of colorectal liver metastases. There is consensus that a histological positive resection margin is a predictor of disease recurrence after resection of colorectal liver metastases. The dispute, however, over the width of cancer-free resection margin required is ongoing. Analysis of observational prospectively collected data for 2715 patients who underwent primary resection of colorectal liver metastases from 2 major hepatobiliary units in the United Kingdom. Histological cancer-free resection margin was classified as positive (if cancer cells present at less than 1 mm from the resection margin) or negative (if the distance between the cancer and the margin is 1 mm or more). The negative margin was further classified according to the distance from the tumor in millimeters. Predictors of disease-free survival were analyzed in univariate and multivariate analyses. A case-match analysis by a propensity score method was undertaken to reduce bias. A 1-mm cancer-free resection margin was sufficient to achieve 33% 5-year overall disease-free survival. Extra margin width did not add disease-free survival advantage (P > 0.05). After the propensity case-match analysis, there is no statistical difference in disease-free survival between patients with negative narrow and wider margin clearance [hazard ratio (HR) 1.0; 95% (confidence interval) CI: 0.9-1.2; P = 0.579 at 5-mm cutoff and HR 1.1; 95% CI: 0.96-1.3; P = 0.149 at 10-mm cutoff]. Patients with extrahepatic disease and positive lymph node primary tumor did not have disease-free survival advantage despite surgical margin clearance (9 months for <1-mm vs 12 months for ≥1-mm margin clearance; P = 0.062). One-mm cancer-free resection margin achieved in patients with colorectal liver metastases should now be considered the standard of care.

Significance of post-resection tissue shrinkage on surgical margins of oral squamous cell carcinoma.

PubMed

El-Fol, Hossam Abdelkader; Noman, Samer Abduljabar; Beheiri, Mohamed Galal; Khalil, Abdalla M; Kamel, Mahmoud Mohamed

2015-05-01

Resecting oral squamous cell carcinoma (SCC) with an appropriate margin of uninvolved tissue is critical in preventing local recurrence and in making decisions regarding postoperative radiation therapy. This task can be difficult due to the discrepancy between margins measured intraoperatively and those measured microscopically by the pathologist after specimen processing. A total of 61 patients underwent resective surgery with curative intent for primary oral SCC were included in this study. All patients underwent resection of the tumor with a measured 1-cm margin. Specimens were then submitted for processing and reviewing, and histopathologic margins were measured. The closest histopathologic margin was compared with the in situ margin (1 cm) to determine the percentage discrepancy. The mean discrepancy between the in situ margins and the histopathological margins of all close and positive margins were 47.6% for the buccal mucosa (with a P value corresponding to 0.05 equaling 2.1), which is statistically significant, 4.8% for the floor of mouth, 9.5% for the mandibular alveolus, 4.8% for the retromolar trigon, and 33.3% for the tongue. There is a significant difference among resection margins based on tumor anatomical location. Margins shrinkage after resection and processing should be considered at the time of the initial resection. Tumors located in the buccal mucosa show significantly greater discrepancies than tumors at other sites. These findings suggest that it is critical to consider the oral site when outlining margins to ensure adequacy of resection. Buccal SCC is an aggressive disease, and should be considered as an aggressive subsite within the oral cavity, requiring a radical and aggressive resective approach. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Optic nerve gliomas: role of Ki-67 staining of tumour and margins in predicting long-term outcome.

PubMed

Yeung, Sonia N; White, Valerie A; Nimmo, Michael; Rootman, Jack

2011-08-01

Although optic nerve gliomas (ONGs) are generally slow-growing with a good prognosis, factors for identifying cases that may pursue a more aggressive course are not well established. The authors investigated cell proliferation markers for prognostic significance in a series of resected ONGs. Twelve cases of resected ONG were identified out of a total of 38 examined at the authors' institution between 1981 and 2008. Clinical data were reviewed. Ki-67 and p53 immunohistochemical staining was performed on the tumour mass and the proximal resection margin. All of the tumours were low-grade pilocytic astrocytomas. Six patients were suspected to have histologically positive proximal resection margins. Ki-67 labelling indices (LI) ranged from 0.3% to 5.9% (mean 2.4%) for the tumour mass and from 0 to 2.1% (mean 0.9%) for the proximal resection margins. One patient had evidence of progression 25 months after subtotal surgical resection. The Ki-67 LI of the proximal resection margin in this case was similar to the main tumour value. The other six patients with histologically negative proximal resection margins all had lower relative proliferation indices at the resection margin when compared with the tumour mass and are currently stable with no evidence of progression. Routine histological examination of resection margins may be difficult to interpret in the setting of reactive gliosis. A resection margin with a Ki-67 LI similar to the tumour bulk value may have an adjunctive role in identifying cases with the potential for growth thereby facilitating the decision-making process for future management and surveillance.

Transanal total mesorectal excision: pathological results of 186 patients with mid and low rectal cancer.

PubMed

de Lacy, F Borja; van Laarhoven, Jacqueline J E M; Pena, Romina; Arroyave, María Clara; Bravo, Raquel; Cuatrecasas, Miriam; Lacy, Antonio M

2018-05-01

Transanal total mesorectal excision (TaTME) seems to be a valid alternative to the open or laparoscopic TME. Quality of the TME specimen is the most important prognostic factor in rectal cancer. This study shows the pathological results of the largest single-institution series published on TaTME in patients with mid and low rectal cancer. We conducted a retrospective cohort study of all consecutive patients with rectal cancer, treated by TaTME between November 2011 and June 2016. Patient data were prospectively included in a standardized database. Patients with all TNM stages of mid (5-10 cm from the anal verge) and low (0-5 cm from the anal verge) rectal cancer were included. A total of 186 patients were included. Tumor was in the mid and low rectum in, respectively, 62.9 and 37.1%. Neoadjuvant chemoradiotherapy was given in 62.4%, only radiotherapy in 3.2%, and only chemotherapy in 2.2%. Preoperative staging showed T1 in 3.2%, T2 in 20.4%, T3 in 67.7%, and T4 in 7.5%. Mesorectal resection quality was complete in 95.7% (n = 178), almost complete in 1.6% (n = 3), and incomplete in 1.1% (n = 2). Overall positive CRM (≤ 1 mm) and DRM (≤ 1 mm) were 8.1% (n = 15) and 3.2% (n = 6), respectively. The composite of complete mesorectal excision, negative CRM, and negative DRM was achieved in 88.1% (n = 155) of the patients. The median number of lymph nodes found per specimen was 14.0 (IQR 11-18). The present study showed good rates regarding total mesorectal excision, negative circumferential, and distal resection margins. As the specimen quality is a surrogate marker for survival, TaTME can be regarded as a safe method to treat patients with rectal cancer, from an oncological point of view.

Oxaliplatin Plus Dual Inhibition of Thymidilate Synthase During Preoperative Pelvic Radiotherapy for Locally Advanced Rectal Carcinoma: Long-Term Outcome

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

Avallone, Antonio, E-mail: avalloneantonio@libero.i; Delrio, Paolo; Pecori, Biagio

Purpose: To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma. Methods and Materials: Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of {<=}5 cm from the anal verge and/or with a circumferential resection margin (CRM) of {<=}5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m{sup 2}; raltitrexed (RTX), 2.5 mg/m{sup 2} on day 1, and 5-fluorouracil (5-FU), 900 mg/m{sup 2} (31 patients) or 800 mg/m{sup 2} (32 patients);more » levo-folinic acid (LFA), 250 mg/m{sup 2} on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve. Results: Overall, neutropenia (40%) and diarrhea (13%) were the most common grade {>=}3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%-92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group. Conclusions: OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.« less

Circumferential resection margin positivity after preoperative chemoradiotherapy based on magnetic resonance imaging for locally advanced rectal cancer: implication of boost radiotherapy to the involved mesorectal fascia.

PubMed

Kim, Kyung Hwan; Park, Min Jung; Lim, Joon Seok; Kim, Nam Kyu; Min, Byung Soh; Ahn, Joong Bae; Kim, Tae Il; Kim, Ho Geun; Koom, Woong Sub

2016-04-01

To identify patients who are at a higher risk of pathologic circumferential resection margin involvement using preoperative magnetic resonance imaging. Between October 2008 and November 2012, 165 patients with locally advanced rectal cancer (cT4 or cT3 with <2 mm distance from tumour to mesorectal fascia) who received preoperative chemoradiotherapy were analysed. The morphologic patterns on post-chemoradiotherapy magnetic resonance imaging were categorized into five patterns from Pattern A (most-likely negative pathologic circumferential resection margin) to Pattern E (most-likely positive pathologic circumferential resection margin). In addition, the location of mesorectal fascia involvement was classified as lateral, posterior and anterior. The diagnostic accuracy of the morphologic criteria was calculated using receiver operating characteristic curve analysis. Pathologic circumferential resection margin involvement was identified in 17 patients (10.3%). The diagnostic accuracy of predicting pathologic circumferential resection margin involvement was 0.73 using the five-scale magnetic resonance imaging pattern. The sensitivity, specificity, positive predictive value and negative predictive value for predicting pathologic circumferential resection margin involvement were 76.5, 65.5, 20.3 and 96.0%, respectively, when cut-off was set between Patterns C and D. On multivariate logistic regression, the magnetic resonance imaging patterns D and E (P= 0.005) and posterior or lateral mesorectal fascia involvement (P= 0.017) were independently associated with increased probability of pathologic circumferential resection margin involvement. The rate of pathologic circumferential resection margin involvement was 30.0% when the patient had Pattern D or E with posterior or lateral mesorectal fascia involvement. Patients who are at a higher risk of pathologic circumferential resection margin involvement can be identified using preoperative magnetic resonance imaging although the predictability is moderate. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Rectal cancer staging: focus on the prognostic significance of the findings described by high-resolution magnetic resonance imaging

PubMed Central

2013-01-01

Abstract High-resolution (HR) magnetic resonance imaging (MRI) has become an indispensable tool for multidisciplinary teams (MDTs) addressing rectal cancer. It provides anatomic information for surgical planning and allows patients to be stratified into different groups according to the risk of local and distant recurrence. One of the objectives of the MDT is the preoperative identification of high-risk patients who will benefit from neoadjuvant treatment. For this reason, the correct evaluation of the circumferential resection margin (CRM), the depth of tumor spread beyond the muscularis propria, extramural vascular invasion and nodal status is of the utmost importance. Low rectal tumors represent a special challenge for the MDT, because decisions seek a balance between oncologic safety, in the pursuit of free resection margins, and the patient’s quality of life, in order to preserve sphincter function. At present, the exchange of information between the different specialties involved in dealing with patients with rectal cancer can rank the contribution of colleagues, auditing their work and incorporating knowledge that will lead to a better understanding of the pathology. Thus, beyond the anatomic description of the images, the radiologist’s role in the MDT makes it necessary to know the prognostic value of the findings that we describe, in terms of recurrence and survival, because these findings affect decision making and, therefore, the patients’ life. In this review, the usefulness of HR MRI in the initial staging of rectal cancer and in the evaluation of neoadjuvant treatment, with a focus on the prognostic value of the findings, is described as well as the contribution of HR MRI in assessing patients with suspected or confirmed recurrence of rectal cancer. PMID:23876415

Rectal cancer staging: focus on the prognostic significance of the findings described by high-resolution magnetic resonance imaging.

PubMed

Dieguez, Adriana

2013-07-22

High-resolution (HR) magnetic resonance imaging (MRI) has become an indispensable tool for multidisciplinary teams (MDTs) addressing rectal cancer. It provides anatomic information for surgical planning and allows patients to be stratified into different groups according to the risk of local and distant recurrence. One of the objectives of the MDT is the preoperative identification of high-risk patients who will benefit from neoadjuvant treatment. For this reason, the correct evaluation of the circumferential resection margin (CRM), the depth of tumor spread beyond the muscularis propria, extramural vascular invasion and nodal status is of the utmost importance. Low rectal tumors represent a special challenge for the MDT, because decisions seek a balance between oncologic safety, in the pursuit of free resection margins, and the patient's quality of life, in order to preserve sphincter function. At present, the exchange of information between the different specialties involved in dealing with patients with rectal cancer can rank the contribution of colleagues, auditing their work and incorporating knowledge that will lead to a better understanding of the pathology. Thus, beyond the anatomic description of the images, the radiologist's role in the MDT makes it necessary to know the prognostic value of the findings that we describe, in terms of recurrence and survival, because these findings affect decision making and, therefore, the patients' life. In this review, the usefulness of HR MRI in the initial staging of rectal cancer and in the evaluation of neoadjuvant treatment, with a focus on the prognostic value of the findings, is described as well as the contribution of HR MRI in assessing patients with suspected or confirmed recurrence of rectal cancer.

Advances in Bio-Optical Imaging for the Diagnosis of Early Oral Cancer

PubMed Central

Olivo, Malini; Bhuvaneswari, Ramaswamy; Keogh, Ivan

2011-01-01

Oral cancer is among the most common malignancies worldwide, therefore early detection and treatment is imperative. The 5-year survival rate has remained at a dismal 50% for the past several decades. The main reason for the poor survival rate is the fact that most of the oral cancers, despite the general accessibility of the oral cavity, are not diagnosed until the advanced stage. Early detection of the oral tumors and its precursor lesions may be the most effective means to improve clinical outcome and cure most patients. One of the emerging technologies is the use of non-invasive in vivo tissue imaging to capture the molecular changes at high-resolution to improve the detection capability of early stage disease. This review will discuss the use of optical probes and highlight the role of optical imaging such as autofluorescence, fluorescence diagnosis (FD), laser confocal endomicroscopy (LCE), surface enhanced Raman spectroscopy (SERS), optical coherence tomography (OCT) and confocal reflectance microscopy (CRM) in early oral cancer detection. FD is a promising method to differentiate cancerous lesions from benign, thus helping in the determination of adequate resolution of surgical resection margin. LCE offers in vivo cellular imaging of tissue structures from surface to subsurface layers and has demonstrated the potential to be used as a minimally invasive optical biopsy technique for early diagnosis of oral cancer lesions. SERS was able to differentiate between normal and oral cancer patients based on the spectra acquired from saliva of patients. OCT has been used to visualize the detailed histological features of the oral lesions with an imaging depth down to 2–3 mm. CRM is an optical tool to noninvasively image tissue with near histological resolution. These comprehensive diagnostic modalities can also be used to define surgical margin and to provide a direct assessment of the therapeutic effectiveness. PMID:24310585

Risk Factors Associated With Circumferential Resection Margin Positivity in Rectal Cancer: A Binational Registry Study.

PubMed

Warrier, Satish K; Kong, Joseph Cherng; Guerra, Glen R; Chittleborough, Timothy J; Naik, Arun; Ramsay, Robert G; Lynch, A Craig; Heriot, Alexander G

2018-04-01

Rectal cancer outcomes have improved with the adoption of a multidisciplinary model of care. However, there is a spectrum of quality when viewed from a national perspective, as highlighted by the Consortium for Optimizing the Treatment of Rectal Cancer data on rectal cancer care in the United States. The aim of this study was to assess and identify predictors of circumferential resection margin involvement for rectal cancer across Australasia. A retrospective study from a prospectively maintained binational colorectal cancer database was interrogated. This study is based on a binational colorectal cancer audit database. Clinical information on all consecutive resected rectal cancer cases recorded in the registry from 2007 to 2016 was retrieved, collated, and analyzed. The primary outcome measure was positive circumferential resection margin, measured as a resection margin ≤1 mm. A total of 3367 patients were included, with 261 (7.5%) having a positive circumferential resection margin. After adjusting for hospital and surgeon volume, hierarchical logistic regression analysis identified a 6-variable model encompassing the independent predictors, including urgent operation, abdominoperineal resection, open technique, low rectal cancer, T3 to T4, and N1 to N2. The accuracy of the model was 92.3%, with an receiver operating characteristic of 0.783 (p < 0.0001). The quantitative risk associated with circumferential resection margin positivity ranged from <1% (no risk factors) to 43% (6 risk factors). This study was limited by the lack of recorded long-term outcomes associated with circumferential resection margin positivity. The rate of circumferential resection margin involvement in patients undergoing rectal cancer resection in Australasia is low and is influenced by a number of factors. Risk stratification of outcome is important with the increasing demand for publicly accessible quality data. See Video Abstract at http://links.lww.com/DCR/A512.

Metastasis Infiltration: An Investigation of the Postoperative Brain-Tumor Interface

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

Raore, Bethwel; Schniederjan, Matthew; Prabhu, Roshan

Purpose: This study aims to evaluate brain infiltration of metastatic tumor cells past the main tumor resection margin to assess the biological basis for the use of stereotactic radiosurgery treatment of the tumor resection cavity and visualized resection edge or clinical target volume. Methods and Materials: Resection margin tissue was obtained after gross total resection of a small group of metastatic lesions from a variety of primary sources. The tissue at the border of the tumor and brain tissue was carefully oriented and processed to evaluate the presence of tumor cells within brain tissue and their distance from the resectionmore » margin. Results: Microscopic assessment of the radially oriented tissue samples showed no tumor cells infiltrating the surrounding brain tissue. Among the positive findings were reactive astrocytosis observed on the brain tissue immediately adjacent to the tumor resection bed margin. Conclusions: The lack of evidence of metastatic tumor cell infiltration into surrounding brain suggests the need to target only a narrow depth of the resection cavity margin to minimize normal tissue injury and prevent treatment size-dependent stereotactic radiosurgery complications.« less

Margin Status Remains an Important Determinant of Survival after Surgical Resection of Colorectal Liver Metastases in the Era of Modern Chemotherapy

PubMed Central

Andreou, Andreas; Aloia, Thomas A.; Brouquet, Antoine; Dickson, Paxton V.; Zimmitti, Giuseppe; Maru, Dipen M.; Kopetz, Scott; Loyer, Evelyne M.; Curley, Steven A.; Abdalla, Eddie K.; Vauthey, Jean-Nicolas

2013-01-01

Objective To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases (CLM) after modern preoperative chemotherapy. Summary Background Data In the era of effective chemotherapy for CLM, the association between surgical margin status and survival has become controversial. Methods Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. Results Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin < 1 mm). The 5-year OS rates for patients with R0 resection (margin ≥ 1 mm) and R1 resection were 55% and 26%, respectively (P=0.017). Multivariate analysis identified R1 resection (P=0.03) and minor pathologic response to chemotherapy (P=0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs. R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs. 11%, P=0.007) than in patients with optimal response (3-year OS rate: 92% vs. 88%, P=0.917) and greater in patients with minor pathologic response (5-year OS rate: 46% vs. 0%, P=0.002) than in patients with major response (5-year OS rate: 63% vs. 67%, P=0.587). Conclusions In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy. PMID:23426338

Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy.

PubMed

Andreou, Andreas; Aloia, Thomas A; Brouquet, Antoine; Dickson, Paxton V; Zimmitti, Giuseppe; Maru, Dipen M; Kopetz, Scott; Loyer, Evelyne M; Curley, Steven A; Abdalla, Eddie K; Vauthey, Jean-Nicolas

2013-06-01

To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases after modern preoperative chemotherapy. In the era of effective chemotherapy for colorectal liver metastases, the association between surgical margin status and survival has become controversial. Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin <1 mm). The 5-year OS rates for patients with R0 resection (margin ≥1 mm) and R1 resection were 55% and 26%, respectively (P = 0.017). Multivariate analysis identified R1 resection (P = 0.03) and a minor pathologic response to chemotherapy (P = 0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs 11%; P = 0.007) than in patients with optimal response (3-year OS rate: 92% vs 88%; P = 0.917) and greater in patients with a minor pathologic response (5-year OS rate: 46% vs 0%; P = 0.002) than in patients with a major response (5-year OS rate: 63% vs 67%; P = 0.587). In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy.

The impact of caudate lobe resection on margin status and outcomes in patients with hilar cholangiocarcinoma: a multi-institutional analysis from the US Extrahepatic Biliary Malignancy Consortium.

PubMed

Bhutiani, Neal; Scoggins, Charles R; McMasters, Kelly M; Ethun, Cecilia G; Poultsides, George A; Pawlik, Timothy M; Weber, Sharon M; Schmidt, Carl R; Fields, Ryan C; Idrees, Kamran; Hatzaras, Ioannis; Shen, Perry; Maithel, Shishir K; Martin, Robert C G

2018-04-01

The objective of this study was to determine the impact of caudate resection on margin status and outcomes during resection of extrahepatic hilar cholangiocarcinoma. A database of 1,092 patients treated for biliary malignancies at institutions of the Extrahepatic Biliary Malignancy Consortium was queried for individuals undergoing curative-intent resection for extrahepatic hilar cholangiocarcinoma. Patients who did versus did not undergo concomitant caudate resection were compared with regard to demographic, baseline, and tumor characteristics as well as perioperative outcomes. A total of 241 patients underwent resection for a hilar cholangiocarcinoma, of whom 85 underwent caudate resection. Patients undergoing caudate resection were less likely to have a final positive margin (P = .01). Kaplan-Meier curve of overall survival for patients undergoing caudate resection indicated no improvement over patients not undergoing caudate resection (P = .16). On multivariable analysis, caudate resection was not associated with improved overall survival or recurrence-free survival, although lymph node positivity was associated with worse overall survival and recurrence-free survival, and adjuvant chemoradiotherapy was associated with improved overall survival and recurrence-free survival. Caudate resection is associated with a greater likelihood of margin-negative resection in patients with extrahepatic hilar cholangiocarcinoma. Precise preoperative imaging is critical to assess the extent of biliary involvement, so that all degrees of hepatic resections are possible at the time of the initial operation. Copyright © 2017 Elsevier Inc. All rights reserved.

Post-resection mucosal margin shrinkage in oral cancer: quantification and significance.

PubMed

Mistry, Rajesh C; Qureshi, Sajid S; Kumaran, C

2005-08-01

The importance of tumor free margins in outcome of cancer surgery is well known. Often the pathological margins are reported to be significantly smaller than the in situ margins. This discrepancy is due to margin shrinkage the quantum of which has not been studied in patients with oral cancers. To quantify the shrinkage of mucosal margin following excision for carcinoma of the oral tongue and buccal mucosa. Mucosal margins were measured prior to resection and half an hour after excision in 27 patients with carcinoma of the tongue and buccal mucosa. The mean margin shrinkage was assessed and the variables affecting the quantum of shrinkage analyzed. The mean shrinkage from the in situ to the post resection margin status was 22.7% (P < 0.0001). The mean shrinkage of the tongue margins was 23.5%, compared to 21.2% for buccal mucosa margins. The mean shrinkage in T1/T2 tumors (25.6%) was significantly more than in T3/T4 (9.2%, P < 0.011). There is significant shrinkage of mucosal margins after surgery. Hence this should be considered and appropriate margins should be taken at initial resection to prevent the agony of post-operative positive surgical margins. Copyright 2005 Wiley-Liss, Inc.

Surgical quality of wedge resection affects overall survival in patients with early stage non-small cell lung cancer.

PubMed

Ajmani, Gaurav S; Wang, Chi-Hsiung; Kim, Ki Wan; Howington, John A; Krantz, Seth B

2018-07-01

Very few studies have examined the quality of wedge resection in patients with non-small cell lung cancer. Using the National Cancer Database, we evaluated whether the quality of wedge resection affects overall survival in patients with early disease and how these outcomes compare with those of patients who receive stereotactic radiation. We identified 14,328 patients with cT1 to T2, N0, M0 disease treated with wedge resection (n = 10,032) or stereotactic radiation (n = 4296) from 2005 to 2013 and developed a subsample of propensity-matched wedge and radiation patients. Wedge quality was grouped as high (negative margins, >5 nodes), average (negative margins, ≤5 nodes), and poor (positive margins). Overall survival was compared between patients who received wedge resection of different quality and those who received radiation, adjusting for demographic and clinical variables. Among patients who underwent wedge resection, 94.6% had negative margins, 44.3% had 0 nodes examined, 17.1% had >5 examined, and 3.0% were nodally upstaged; 16.7% received a high-quality wedge, which was associated with a lower risk of death compared with average-quality resection (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], 0.67-0.82). Compared with stereotactic radiation, wedge patients with negative margins had significantly reduced hazard of death (>5 nodes: aHR, 0.50; 95% CI, 0.43-0.58; ≤5 nodes: aHR, 0.65; 95% CI, 0.60-0.70). There was no significant survival difference between margin-positive wedge and radiation. Lymph nodes examined and margins obtained are important quality metrics in wedge resection. A high-quality wedge appears to confer a significant survival advantage over lower-quality wedge and stereotactic radiation. A margin-positive wedge appears to offer no benefit compared with radiation. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Prognostic significance of positive circumferential resection margin in esophageal cancer: a systematic review and meta-analysis.

PubMed

Wu, Jie; Chen, Qi-Xun; Teng, Li-song; Krasna, Mark J

2014-02-01

To assess the prognostic significance of positive circumferential resection margin on overall survival in patients with esophageal cancer, a systematic review and meta-analysis was performed. Studies were identified from PubMed, EMBASE, and Web of Science. Survival data were extracted from eligible studies to compare overall survival in patients with a positive circumferential resection margin with patients having a negative circumferential resection margin according to the Royal College of Pathologists (RCP) criteria and the College of American Pathologists (CAP) criteria. Survival data were pooled with hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). A random-effects model meta-analysis on overall survival was performed. The pooled HRs for survival were 1.510 (95% CI, 1.329-1.717; p<0.001) and 2.053 (95% CI, 1.597-2.638; p<0.001) according to the RCP and CAP criteria, respectively. Positive circumferential resection margin was associated with worse survival in patients with T3 stage disease according to the RCP (HR, 1.381; 95% CI, 1.028-1.584; p=0.001) and CAP (HR, 2.457; 95% CI, 1.902-3.175; p<0.001) criteria, respectively. Positive circumferential resection margin was associated with worse survival in patients receiving neoadjuvant therapy according to the RCP (HR, 1.676; 95% CI, 1.023-2.744; p=0.040) and CAP (HR, 1.847; 95% CI, 1.226-2.78; p=0.003) criteria, respectively. Positive circumferential resection margin is associated with poor prognosis in patients with esophageal cancer, particularly in patients with T3 stage disease and patients receiving neoadjuvant therapy. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The assessment of mucosal surgical margins in head and neck cancer surgery with narrow band imaging.

PubMed

Šifrer, Robert; Urbančič, Jure; Strojan, Primož; Aničin, Aleksandar; Žargi, Miha

2017-07-01

The diagnostic gain of narrow band imaging in the definition of surgical margins in the treatment of head and neck cancer was evaluated. A prospective study, blinded to the pathologist, with historical comparison. The study group included 45 patients subjected to the intraoperative definition of margins by narrow band imaging. The control group included 55 patients who had undergone standard definition of margins. All patients underwent resection of the tumor and frozen section analysis of superficial margins. The rate of initial R 0 resection and the ratio of histologically negative margins for both groups were statistically compared. The rate of initial R 0 resection in the study group and in the control group was 88.9% and 70.9% (P = .047), and the ratio of histologically negative margins was 95.9% and 88.4% (P = .017), respectively. Narrow band imaging reveals a microscopic extension of the tumor that could be effectively used to better define superficial margins and to achieve a higher rate of initial R 0 resections. 4 Laryngoscope, 127:1577-1582, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Is intralesional resection suitable for central grade 1 chondrosarcoma: A systematic review and updated meta-analysis.

PubMed

Chen, X; Yu, L J; Peng, H M; Jiang, C; Ye, C H; Zhu, S B; Qian, W W

2017-09-01

The surgical choice for grade 1 chondrosarcoma has been debated for decades. Intralesional resection can minimize the damage caused by surgery and offer better functional outcome. However, controversy remains about whether it will result in higher rates of local recurrence and metastasis, fewer complications, and better functional outcome compared with resection with wide margin. This systematic review and updated meta-analysis therefore compared intralesional resection and resection with wide margin in terms of local recurrence, metastasis, complications, and functional outcome. Medline, Embase, and the Cochrane Library were comprehensively searched in December 2016 to identify studies comparing intralesional resection and resection with wide margin for central grade 1 chondrosarcoma. Data of interest were extracted and analyzed using Review Manager 5.3. Ten studies involving 394 patients were included, with 214 patients who had intralesional resection and 180 patients who had resection with wide margin for grade 1 chondrosarcoma. Intralesional resection was associated with lower complication rates (P < 0.0001) and better Musculoskeletal Tumor Society score (MSTS). There were no significant differences in terms of overall local recurrence (P = 0.27), local recurrence based on adjuvant therapies (P = 0.22), local recurrence in studies that included lesions of the hand, foot, pelvis, and axial skeleton (P = 0.55), and metastasis (P = 0.74) between groups. Intralesional resection provides lower complications and better functional outcome with no significant increase in the risk of recurrence and metastasis. We think it is a suitable treatment for central grade 1 chondrosarcoma. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Preliminary Outcome of Individualized Abdominoperineal Excision for Locally Advanced Low Rectal Cancer.

PubMed

Zheng, Yi; Han, Jia-Gang; Wang, Zhen-Jun; Gao, Zhi-Gang; Wei, Guang-Hui; Zhai, Zhi-Wei; Zhao, Bao-Cheng

2018-06-05

The introduction of individualized abdominoperineal excision (APE) may minimize operative trauma and reduce the rate of complications. The purpose of this study was to evaluate the safety and efficacy of individualized APE for low rectal cancer. Fifty-six patients who underwent individualized APE from June 2011 to June 2015 were evaluated retrospectively in Beijing Chaoyang Hospital, Capital Medical University. The main outcome measures were circumferential resection margin (CRM) involvement, intraoperative perforation, postoperative complications, and local recurrence. Statistical analysis was performed using SPSS version 16.0. Fifty (89%) patients received preoperative chemoradiotherapy: 51 (91%) patients were treated with the sacrococcyx preserved; 27 (48%) patients with the levator ani muscle partially preserved bilaterally; 20 (36%) patients with the levator ani muscle partially preserved unilaterally and the muscle on the opposite side totally preserved; 7 (13%) patients with intact levator ani muscle and part of the ischioanal fat bilaterally dissected; and 2 (4%) patients with part of the ischioanal fat and intact lavator ani muscle dissected unilaterally and the muscle on the opposite side partially preserved. The most common complications included sexual dysfunction (12%), perineal wound complications (13%), urinary retention (7%), and chronic perineal pain (5%). A positive CRM was demonstrated in 3 (5%) patients, and intraoperative perforations occurred in 2 (4%) patients. On multiple logistic regression analysis, longer operative time (P = 0.032) and more intraoperative blood loss (P = 0.006) were significantly associated with perineal procedure-related complications. The local recurrence was 4% at a median follow-up of 53 months (range: 30-74 months). With preoperative chemoradiotherapy, individualized APE may be a relatively safe and feasible approach for low rectal cancer with acceptable oncological outcomes.

Factors affecting surgical margin recurrence after hepatectomy for colorectal liver metastases.

PubMed

Akyuz, Muhammet; Aucejo, Federico; Quintini, Cristiano; Miller, Charles; Fung, John; Berber, Eren

2016-06-01

Hepatic recurrence after resection of colorectal liver metastasis (CLM) occurs in 50% of patients during follow-up, with 2.8% to 13.9% presenting with surgical margin recurrence (SMR). The aim of this study is to analyze factors that related to SMR in patients with CLM undergoing hepatectomy. Demographics, clinical and survival data of patients who underwent hepatectomy were identified from a prospectively maintained, institutional review board (IRB)-approved database between 2000 and 2012. Statistical analysis was performed using univariate Kaplan Meier and Cox proportional hazard model. There were 85 female and 121 male patients who underwent liver resection for CLM. An R0 resection was performed in 157 (76%) patients and R1 resection in 49. SMR was detected in 32 patients (15.5%) followed up for a median of 29 months (range, 3-121 months). A half of these patients had undergone R1 (n=16) and another half R0 resection (n=16). Tumor size, preoperative carcinoembryonic antigen (CEA) level and margin status were associated with SMR on univariate analysis. On multivariate analysis, a positive surgical margin was the only independent predictor of SMR. The receipt of adjuvant chemotherapy did not affect margin recurrence. SMR was an independent risk factor associated with worse disease-free (DFS) and overall survival (OS). This study shows that SMR, which can be detected in up to 15.5% of patients after liver resection for CLM, adversely affects DFS and OS. The fact that a positive surgical margin was the only predictive factor for SMR in these patients underscores the importance of achieving negative margins during hepatectomy.

Dermatofibrosarcoma protuberans of the vulva: margins assessment and reconstructive options - a report of two cases.

PubMed

Bertolli, Eduardo; Bretchbuhl, Eduard Renè; Camarço, William Ricardo; Campagnari, Mariane; Molina, André Sapata; Baiocchi, Glauco; Macedo, Mariana Petaccia; Pinto, Clovis Antonio; Cunha, Isabela Werneck; Neto, João Pedreira

2014-12-29

Dermatofibrosarcoma Protuberans (DFSP) of the vulva is rare and oncologic surgery with free margins may lead to severe functional damage, requiring multidisciplinary approach regarding resection, margin assessment and reconstruction.Case Report: Two cases of DFSP in vulva were treated in a single institution. A 28-year-old patient with an incisional biopsy in the vulvar region revealing DFSP underwent a partial vulvectomy with clitoris preservation. Pathological studies revealed free margins and reconstructive surgery was performed. This patient is disease free in a 40 months follow up. The other, a 57-year-old patient was also referred after an incomplete resection of a DFSP in the vulvar region. A 1-cm margim resection followed by Complete Circumferential and Peripheral Deep Margin Assessment (CCPDMA) was performed. Although the upper lateral margin was positive, it was possible to perform another wide local excision with preservation of the clitoris and primary closure. DFSP of the vulva requires an accurate evaluation of margins, resections following oncological principles and reconstruction. Although being a very challenging lesion that usually implies difficult surgical management, if treated in a multidisciplinary environment, with surgical oncologists, experienced dermatopathologists and reconstructive surgeons can achieve good results. Even in difficult cases that presents with large lesions and compromising challenging areas, a complete oncologic resection can be performed minimizing functional damage for the patient.

Tumor response and negative distal resection margins of rectal cancer after hyperthermochemoradiation therapy.

PubMed

Tsutsumi, Soichi; Tabe, Yuichi; Fujii, Takaaki; Yamaguchi, Satoru; Suto, Toshinaga; Yajima, Reina; Morita, Hiroki; Kato, Toshihide; Shioya, Mariko; Saito, Jun-Ichi; Asao, Takayuki; Nakano, Takashi; Kuwano, Hiroyuki

2011-11-01

The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method. Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival. Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the <10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival. Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.

MRI Evaluation of Resection Margins in Bone Tumour Surgery

PubMed Central

Traore, Sidi Yaya; Lecouvet, Frédéric; Galant, Christine

2014-01-01

In 12 patients operated on for bone sarcoma resection, a postoperative magnetic resonance imaging of the resection specimens was obtained in order to assess the surgical margins. Margins were classified according to MRI in R0, R1, and R2 by three independent observers: a radiologist and two orthopaedic surgeons. Final margin evaluation (R0, R1, and R2) was assessed by a confirmed pathologist. Agreement for margin evaluation between the pathologist and the radiologist was perfect (κ = 1). Agreement between the pathologist and an experienced orthopaedic surgeon was very good while it was fair between the pathologist and a junior orthopaedic surgeon. MRI should be considered as a tool to give quick information about the adequacy of margins and to help the pathologist to focus on doubtful areas and to spare time in specimen analysis. But it may not replace the pathological evaluation that gives additional information about tumor necrosis. This study shows that MRI extemporaneous analysis of a resection specimen may be efficient in bone tumor oncologic surgery, if made by an experienced radiologist with perfect agreement with the pathologist. PMID:24976785

Augmented reality in a tumor resection model.

PubMed

Chauvet, Pauline; Collins, Toby; Debize, Clement; Novais-Gameiro, Lorraine; Pereira, Bruno; Bartoli, Adrien; Canis, Michel; Bourdel, Nicolas

2018-03-01

Augmented Reality (AR) guidance is a technology that allows a surgeon to see sub-surface structures, by overlaying pre-operative imaging data on a live laparoscopic video. Our objectives were to evaluate a state-of-the-art AR guidance system in a tumor surgical resection model, comparing the accuracy of the resection with and without the system. Our system has three phases. Phase 1: using the MRI images, the kidney's and pseudotumor's surfaces are segmented to construct a 3D model. Phase 2: the intra-operative 3D model of the kidney is computed. Phase 3: the pre-operative and intra-operative models are registered, and the laparoscopic view is augmented with the pre-operative data. We performed a prospective experimental study on ex vivo porcine kidneys. Alginate was injected into the parenchyma to create pseudotumors measuring 4-10 mm. The kidneys were then analyzed by MRI. Next, the kidneys were placed into pelvictrainers, and the pseudotumors were laparoscopically resected. The AR guidance system allows the surgeon to see tumors and margins using classical laparoscopic instruments, and a classical screen. The resection margins were measured microscopically to evaluate the accuracy of resection. Ninety tumors were segmented: 28 were used to optimize the AR software, and 62 were used to randomly compare surgical resection: 29 tumors were resected using AR and 33 without AR. The analysis of our pathological results showed 4 failures (tumor with positive margins) (13.8%) in the AR group, and 10 (30.3%) in the Non-AR group. There was no complete miss in the AR group, while there were 4 complete misses in the non-AR group. In total, 14 (42.4%) tumors were completely missed or had a positive margin in the non-AR group. Our AR system enhances the accuracy of surgical resection, particularly for small tumors. Crucial information such as resection margins and vascularization could also be displayed.

[A cutaneous horn of the free margin of the eyelid: an anatomical and clinical observation].

PubMed

D'Hermies, F; Gerolami-Favreul, I; Meyer, A; Morel, X; Halhal, M; Sam, H; Elmaleh, C; Renard, G; Behar-Cohen, F

2003-05-01

A cutaneous horn was observed close to the free margin of the inferior right eyelid in a 26-year-old-male patient. A minimal resection was primarily performed. Histopathologic study disclosed a precancerous keratosis. As the tumor had not been entirely excised, a complementary resection was performed secondarily to obtain the entire resection of the tumor.

Factors affecting surgical margin recurrence after hepatectomy for colorectal liver metastases

PubMed Central

Akyuz, Muhammet; Aucejo, Federico; Quintini, Cristiano; Miller, Charles; Fung, John

2016-01-01

Background Hepatic recurrence after resection of colorectal liver metastasis (CLM) occurs in 50% of patients during follow-up, with 2.8% to 13.9% presenting with surgical margin recurrence (SMR). The aim of this study is to analyze factors that related to SMR in patients with CLM undergoing hepatectomy. Methods Demographics, clinical and survival data of patients who underwent hepatectomy were identified from a prospectively maintained, institutional review board (IRB)-approved database between 2000 and 2012. Statistical analysis was performed using univariate Kaplan Meier and Cox proportional hazard model. Results There were 85 female and 121 male patients who underwent liver resection for CLM. An R0 resection was performed in 157 (76%) patients and R1 resection in 49. SMR was detected in 32 patients (15.5%) followed up for a median of 29 months (range, 3–121 months). A half of these patients had undergone R1 (n=16) and another half R0 resection (n=16). Tumor size, preoperative carcinoembryonic antigen (CEA) level and margin status were associated with SMR on univariate analysis. On multivariate analysis, a positive surgical margin was the only independent predictor of SMR. The receipt of adjuvant chemotherapy did not affect margin recurrence. SMR was an independent risk factor associated with worse disease-free (DFS) and overall survival (OS). Conclusions This study shows that SMR, which can be detected in up to 15.5% of patients after liver resection for CLM, adversely affects DFS and OS. The fact that a positive surgical margin was the only predictive factor for SMR in these patients underscores the importance of achieving negative margins during hepatectomy. PMID:27294032

Surgical margin-negative endoscopic mucosal resection with simple three-clipping technique: a randomized prospective study (with video).

PubMed

Mori, Hirohito; Kobara, Hideki; Nishiyama, Noriko; Fujihara, Shintaro; Kobayashi, Nobuya; Ayaki, Maki; Masaki, Tsutomu

2016-11-01

Although endoscopic mucosal resection is an established colorectal polyp treatment, local recurrence occurs in 13 % of cases due to inadequate snaring. We evaluated whether pre-clipping to the muscularis propria resulted in resected specimens with negative surgical margins without thermal denaturation. Of 245 polyps from 114 patients with colorectal polyps under 20 mm, we included 188 polyps from 81 patients. We randomly allocated polyps to the conventional injection group (CG) (97 polyps) or the pre-clipping injection group (PG) (91 polyps). The PG received three-point pre-clipping to ensure ample gripping to the muscle layer on the oral and both sides of the tumor with 4 mL local injection. Endoscopic ultrasonography was performed to measure the resulting bulge. Outcomes included the number of instances of thermal denaturation of the horizontal/vertical margin (HMX/VMX) or positive horizontal/vertical margins (HM+/VM+), the shortest distance from tumor margins to resected edges, and the maximum bulge distances from tumor surface to the muscularis propria. The numbers of HMX and HM+ in the CG and PG were 27 and 6, and 9 and 2 (P = 0.001), and VMX and VM+ were 8 and 5, and 0 and 0 (P = 0.057). The shortest distance from tumor margin to resected edge [median (range), mm] in polyps in the CG and PG was 0.6 (0-2.7) and 4.7 (2.1-8.9) (P = 0.018). The maximum bulge distances were 4.6 (3.0-8.0) and 11.0 (6.8-17.0) (P = 0.005). Pre-clipping enabled surgical margin-negative resection without thermal denaturation.

Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

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

Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.

2012-10-01

Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competingmore » risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.« less

Identification of predisposing factors for osteonecrosis of the jaw after marginal mandibulectomy in the surgical management of oral squamous cell carcinoma.

PubMed

Ito, Ran; Huang, Jung-Ju; Hsieh, Wei-Chuan; Kao, Huang-Kai; Lao, William Wei-Kai; Fang, Ku-Hao; Huang, Yenlin; Chang, Yu-Liang; Cheng, Ming-Huei; Chang, Kai-Ping

2018-03-01

The aim of this study is to evaluate osteonecrosis of the jaw (ONJ) with the extent of marginal mandibulectomy. Between January 2006 and December 2012, 3087 patients undergoing ablative resection were consecutively enrolled. Among them, 345 cases undergoing marginal mandibulectomy were retrospectively reviewed. The occurrence of ONJ was 5.51% and associated with body mass index, overall stage, diabetes, concomitant mandibulotomy, and radiotherapy (P = 0.023, 0.033, 0.009, 0.016, and 0.006, respectively). As for bone parameters based on radiological measurements after marginal mandibulectomy, resected bone height, remaining bone height to original bone height ratio, and resected bone height to original bone height ratio were associated with ONJ. In multivariate logistic analyses, concomitant mandibulotomy, radiotherapy, diabetes, resected bone height of >14.5 mm, resected bone height to original bone height ratio of >49.5%, and remaining bone height to original bone height ratio of <53.5% indicated higher risks for ONJ (adjusted HR: 4.345, 4.152, 4.079, 3.402, 3.541, and 3.211; P = 0.018, 0.013, 0.009, 0.021, 0.018, and 0.043, respectively). This study demonstrated the predisposing factors and parameters associated with ONJ with marginal mandibulectomy; more caution is necessitated in performing marginal mandibulectomy in patients with multiple risks to prevent ONJ. © 2017 Wiley Periodicals, Inc.

Therapeutic dormancy to delay postsurgical glioma recurrence: the past, present and promise of focal hypothermia.

PubMed

Wion, Didier

2017-07-01

Surgery precedes both radiotherapy and chemotherapy as the first-line therapy for glioma. However, despite multimodal treatment, most glioma patients die from local recurrence in the resection margin. Glioma surgery is inherently lesional, and the response of brain tissue to surgery includes hemostasis, angiogenesis, reactive gliosis and inflammation. Unfortunately, these processes are also associated with tumorigenic side-effects. An increasing amount of evidence indicates that the response to a surgery-related brain injury is hijacked by residual glioma cells and participates in the local regeneration of tumor tissues at the resection margin. Inducing therapeutic hypothermia in the brain has long been used to treat the secondary damage, such as neuroinflammation and edema, that are caused by accidental traumatic brain injuries. There is compelling evidence to suggest that inducing therapeutic hypothermia at the resection margin would delay the local recurrence of glioma by (i) limiting cell proliferation, (ii) disrupting the pathological connection between inflammation and glioma recurrence, and (iii) limiting the consequences of the functional heterogeneity and complexity inherent to the tumor ecosystem. While the global whole-body cooling methods that are currently used to treat stroke in clinical practice may not adequately treat the resection margin, the future lies in implantable focal microcooling devices similar to those under development for the treatment of epilepsy. Preclinical and clinical strategies to evaluate focal hypothermia must be implemented to prevent glioma recurrence in the resection margin. Placing the resection margin in a state of hibernation may potentially provide such a long-awaited therapeutic breakthrough.

Interventional fluorescence spectroscopy: preliminary results to detect tumor margins during glioma resection with two fluorescence spectra of PpIX

NASA Astrophysics Data System (ADS)

Alston, L. M.; Guyotat, J.; Mahieu-Williame, L.; Hebert, M.; Kantapareddy, P.; Meyronet, D.; Rousseau, D.; Montcel, B.

2017-07-01

We show the feasibility of using an intraoperative spectroscopic device to identify tumors margins during glioma resection. The collected fluorescence spectra is fitted with two reference spectra of PpIX and the contribution of each spectrum enables to overcome the sensitivity of current techniques by seeing tumor margins and low grade gliomas.

Can Navigation-assisted Surgery Help Achieve Negative Margins in Resection of Pelvic and Sacral Tumors?

PubMed

Abraham, John A; Kenneally, Barry; Amer, Kamil; Geller, David S

2018-03-01

Navigation-assisted resection has been proposed as a useful adjunct to resection of malignant tumors in difficult anatomic sites such as the pelvis and sacrum where it is difficult to achieve tumor-free margins. Most of these studies are case reports or small case series, but these reports have been extremely promising. Very few reports, however, have documented benefits of navigation-assisted resection in series of pelvic and sacral primary tumors. Because this technology may add time and expense to the surgical procedure, it is important to determine whether navigation provides any such benefits or simply adds cost and time to an already complex procedure. (1) What proportion of pelvic and sacral bone sarcoma resections utilizing a computer-assisted resection technique achieves negative margins? (2) What are the oncologic outcomes associated with computer-assisted resection of pelvic and sacral bone sarcomas? (3) What complications are associated with navigation-assisted resection? Between 2009 and 2015 we performed 24 navigation-assisted resections of primary tumors of the pelvis or sacrum. Of those, four were lost to followup after the 2-year postoperative visit. In one patient, however, there was a failure of navigation as a result of inadequate imaging, so nonnavigated resection was performed; the remaining 23 were accounted for and were studied here at a mean of 27 months after surgery (range, 12-52 months). During this period, we performed navigation-assisted resections in all patients presenting with a pelvis or sacral tumor; there was no selection process. No patients were treated for primary tumors in these locations without navigation during this time with the exception of the single patient in whom the navigation system failed. We retrospectively evaluated the records of these 23 patients and evaluated the margin status of these resections. We calculated the proportion of patients with local recurrence, development of metastases, and overall survival at an average 27-month followup (range, 12-52 months). We queried a longitudinally maintained surgical database for any complications and noted which, if any, could have been directly related to the use of the navigation-assisted technique. In our series, 21 of 23 patients had a negative margin resection. In all patients the bone margin was negative, but two with sacral resections had positive soft tissue margins. Six of 23 patients experienced local recurrence within the study period. Three patients died during the study period. Seventeen patients demonstrated no evidence of disease at last recorded followup. We noted three intraoperative complications: one dural tear, one iliac vein laceration, and one bladder injury. Eight patients out of 23 had wound complications resulting in operative débridement. Two patients in the series developed transient postoperative femoral nerve palsy, which we believe were caused by stretch of the femoral nerve secondary to the placement of the reference array in the pubic ramus. Navigation-assisted resection of pelvic and sacral tumors resulted in a high likelihood of negative margin resection in this series, and we observed relatively few complications related specifically to the navigation. We have no comparison group without navigation, and future studies should indeed compare navigated with nonnavigated resection approaches in these anatomic locations. We did identify a potential navigation-related complication of femoral nerve palsy in this series and suggest careful placement and observation of the reference array during the operative procedure to lessen the likelihood of this previously unreported complication. We suggest it is worthwhile to consider the use of navigation-assisted surgery in resection of tumors of the pelvis and sacrum, but further study will be needed to determine its precise impact, if any, on local recurrence and other oncologic outcomes. Level IV, therapeutic study.

Cardiovascular Risk and the American Dream: Life Course Observations From the BHS (Bogalusa Heart Study).

PubMed

Pollock, Benjamin D; Harville, Emily W; Mills, Katherine T; Tang, Wan; Chen, Wei; Bazzano, Lydia A

2018-02-06

Economic literature shows that a child's future earnings are predictably influenced by parental income, providing an index of "socioeconomic mobility," or the ability of a person to move towards a higher socioeconomic status from childhood to adulthood. We adapted this economic paradigm to examine cardiovascular risk mobility (CRM), or whether there is life course mobility in relative cardiovascular risk. Participants from the BHS (Bogalusa Heart Study) with 1 childhood and 1 adult visit from 1973 to 2016 (n=7624) were considered. We defined population-level CRM as the rank-rank slope (β) from the regression of adult cardiovascular disease (CVD) risk percentile ranking onto childhood CVD risk percentile ranking (β=0 represents complete mobility; β=1 represents no mobility). After defining and measuring relative CRM, we assessed its correlation with absolute cardiovascular health using the American Heart Association's Ideal Cardiovascular Health metrics. Overall, there was substantial mobility, with black participants having marginally better CRM than whites (β black =0.10 [95% confidence interval, 0.05-0.15]; β white =0.18 [95% confidence interval, 0.14-0.22]; P =0.01). Having high relative CVD risk at an earlier age significantly reduced CRM (β age×slope =-0.02; 95% confidence interval, -0.03 to -0.01; P <0.001). Relative CRM was strongly correlated with life course changes in Ideal Cardiovascular Health sum ( r =0.62; 95% confidence interval, 0.60-0.65). Results from this novel application of an economic mobility index to cardiovascular epidemiology indicated substantial CRM, supporting the paradigm that life course CVD risk is highly modifiable. High CRM implies that the children with the best relative CVD profiles may only maintain a slim advantage over their peers into adulthood. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III Rectal Cancer on Pathologic Outcomes

PubMed Central

Fleshman, James; Branda, Megan; Sargent, Daniel J.; Boller, Anne Marie; George, Virgilio; Abbas, Maher; Peters, Walter R.; Maun, Dipen; Chang, George; Herline, Alan; Fichera, Alessandro; Mutch, Matthew; Wexner, Steven; Whiteford, Mark; Marks, John; Birnbaum, Elisa; Margolin, David; Larson, David; Marcello, Peter; Posner, Mitchell; Read, Thomas; Monson, John; Wren, Sherry M.; Pisters, Peter W. T.; Nelson, Heidi

2016-01-01

IMPORTANCE Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease. OBJECTIVE To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen. DESIGN, SETTING, AND PARTICIPANTS A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection. INTERVENTIONS Standard laparoscopic and open approaches were performed by the credentialed surgeons. MAIN OUTCOMES AND MEASURES The primary outcome assessing efficacy was a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6%noninferiority margin was chosen according to clinical relevance estimation. RESULTS Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7%of laparoscopic resection cases (95%CI, 76.8%–86.6%) and 86.9%of open resection cases (95%CI, 82.5%–91.4%) and did not support noninferiority (difference, −5.3%; 1-sided 95%CI, −10.8%to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7%) or abdominoperineal resection (23.3%). Conversion to open resection occurred in 11.3%of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95%CI, 27.7–63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95%CI, −0.6 to 1.1), readmission within 30 days (3.3%vs 4.1%; difference, −0.7%; 95%CI, −4.2%to 2.7%), and severe complications (22.5%vs 22.1%; difference, 0.4%; 95%CI, −4.2%to 2.7%) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77%) and nearly complete (16.5%) in 93.5%of the cases. Negative circumferential radial margin was observed in 90% of the overall group (87.9% laparoscopic resection and 92.3%open resection; P = .11). Distal margin result was negative in more than 98%of patients irrespective of type of surgery (P = .91). CONCLUSIONS AND RELEVANCE Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00726622 PMID:26441179

Recent technological developments: in situ histopathological interrogation of surgical tissues and resection margins

PubMed Central

Upile, Tahwinder; Fisher, Cyril; Jerjes, Waseem; El Maaytah, Mohammed; Singh, Sandeep; Sudhoff, Holger; Searle, Adam; Archer, Daniel; Michaels, Leslie; Hopper, Colin; Rhys-Evans, Peter; Howard, David; Wright, Anthony

2007-01-01

Objectives The tumour margin is an important surgical concept significantly affecting patient morbidity and mortality. We aimed in this prospective study to apply the microendoscope on tissue margins from patients undergoing surgery for oral cancer in vivo and ex vivo and compare it to the gold standard "paraffin wax", inter-observer agreement was measured; also to present the surgical pathologist with a practical guide to the every day use of the microendoscope both in the clinical and surgical fields. Materials and methods Forty patients undergoing resection of oral squamous cell carcinoma were recruited. The surgical margin was first marked by the operator followed by microendoscopic assessment. Biopsies were taken from areas suggestive of close or positive margins after microendoscopic examination. These histological samples were later scrutinized formally and the resection margins revisited accordingly when necessary. Results Using the microendoscope we report our experience in the determination of surgical margins at operation and later comparison with frozen section and paraffin section margins "gold standard". We were able to obtain a sensitivity of 95% and a specificity of 90%. Inter-observer Kappa scores comparing the microendoscope with formal histological analysis of normal and abnormal mucosa were 0.85. Conclusion The advantage of this technique is that a large area of mucosa can be sampled and any histomorphological changes can be visualized in real time allowing the operator to make important informed decisions with regards the intra-operative resection margin at the time of the surgery. PMID:17331229

Autofluorescence of normal and neoplastic human brain tissue: an aid for intraoperative delineation of tumor resection margins

NASA Astrophysics Data System (ADS)

Bottiroli, Giovanni F.; Croce, Anna C.; Locatelli, Donata; Nano, Rosanna; Giombelli, Ermanno; Messina, Alberto; Benericetti, Eugenio

1998-01-01

Light-induced autofluorescence measurements were made on normal and tumor brain tissues to assess their spectroscopic properties and to verify the potential of this parameter for an intraoperative delineation of tumor resection margins. Spectrofluorometric analysis was performed both at the microscope on tissue sections from surgical resection, and on patients affected by glioblastoma, during surgical operation. Significant differences in autofluorescence emission properties were found between normal and tumor tissues in both ex vivo and in vivo measurements, indicating that the lesion can be distinguished from the informal surrounding tissues by the signal amplitude and the spectral shape. The non-invasiveness of the technique opens interesting prospects for improving the efficacy of neurosurgical operation, by allowing an intraoperative delimitation of tumor resection margins.

[Resection margins in conservative breast cancer surgery].

PubMed

Medina Fernández, Francisco Javier; Ayllón Terán, María Dolores; Lombardo Galera, María Sagrario; Rioja Torres, Pilar; Bascuñana Estudillo, Guillermo; Rufián Peña, Sebastián

2013-01-01

Conservative breast cancer surgery is facing a new problem: the potential tumour involvement of resection margins. This eventuality has been closely and negatively associated with disease-free survival. Various factors may influence the likelihood of margins being affected, mostly related to the characteristics of the tumour, patient or surgical technique. In the last decade, many studies have attempted to find predictive factors for margin involvement. However, it is currently the new techniques used in the study of margins and tumour localisation that are significantly reducing reoperations in conservative breast cancer surgery. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

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

The use of CT derived solid modelling of the pelvis in planning cancer resections.

PubMed

Bruns, J; Habermann, C R; Rüther, W; Delling, D

2010-06-01

Resection of malignant tumors of the pelvis is demanding. To avoid disabling hemipelvectomies, years ago internal hemipelvectomy combined with partial pelvic replacements had become a surgical procedure. To achieve adequate reconstructions custom-made replacements were recommended. In early stages of the surgical procedure using megaprostheses, individual pelvic models were manufactured. Since little is known about the accuracy of such models we analysed the charts of 24 patients (25 models) for whom an individual model of the osseous pelvis had been manufactured. Two patients refused surgery. In 23 patients partial resection of the bony pelvis was performed followed by a partial pelvic replacement (13x), hip transposition procedure (5x), ilio-sacral resection (4x), or revision surgery. In all patients who received a partial pelvic replacement, the fit of the replacement was optimal. No major unplanned resection was necessary. The same was observed in patients who received a hip transposition procedure or an ilio-sacral resection. Oncologically, in most of the patients we achieved wide resection margins (14x). In 5 patients the margins were marginal (4x) or intralesional (1x). In two cases the aim was a palliative resection because of a metastatic disease (1x) or benign entity (1x). Pelvic models are helpful tools to planning the manufacture of partial pelvic replacements and ensuring optimal osseous resection of the involved bone. Further attempts have to be made to evaluate the aim of navigational techniques regarding the accuracy of the osseous and soft-tissue resection.

Hepatic Resection for Colorectal Liver Metastases: A Cost-Effectiveness Analysis

PubMed Central

Beard, Stephen M.; Holmes, Michael; Price, Charles; Majeed, Ali W.

2000-01-01

Objective To analyze the cost-effectiveness of resection for liver metastases compared with standard nonsurgical cytotoxic treatment. Summary Background Data The efficacy of hepatic resection for metastases from colorectal cancer has been debated, despite reported 5-year survival rates of 20% to 40%. Resection is confined to specialized centers and is not widely available, perhaps because of lack of appropriate expertise, resources, or awareness of its efficacy. The cost-effectiveness of resection is important from the perspective of managed care in the United States and for the commissioning of health services in the United Kingdom. Methods A simple decision-based model was developed to evaluate the marginal costs and health benefits of hepatic resection. Estimates of resectability for liver metastases were taken from UK-reported case series data. The results of 100 hepatic resections conducted in Sheffield from 1997 to 1999 were used for the cost calculation of liver resection. Survival data from published series of resections were compiled to estimate the incremental cost per life-year gained (LYG) because of the short period of follow-up in the Sheffield series. Results Hepatic resection for colorectal liver metastases provides an estimated marginal benefit of 1.6 life-years (undiscounted) at a marginal cost of £6,742. If 17% of patients have only palliative resections, the overall cost per LYG is approximately £5,236 (£5,985 with discounted benefits). If potential benefits are extended to include 20-year survival rates, these figures fall to approximately £1,821 (£2,793 with discounted benefits). Further univariate sensitivity analysis of key model parameters showed the cost per LYG to be consistently less than £15,000. Conclusion In this model, hepatic resection appears highly cost-effective compared with nonsurgical treatments for colorectal-related liver metastases. PMID:11088071

[Organ-limited prostate cancer with positive resection margins. Importance of adjuvant radiation therapy].

PubMed

Porres, D; Pfister, D; Brehmer, B; Heidenreich, A

2012-09-01

For pT3 prostate cancer with positive resection margins, the importance of postoperative radiation therapy is confirmed by a high level of evidence. However, for the pT2,R1 situation prospective, randomized studies concerning this question are lacking. Despite better local tumor control in the pT2 stage the PSA recurrence rate lies between 25% and 40% and positive margins are an independent factor for recurrence. Retrospective studies suggest a positive effect of adjuvant or salvage radiation for the oncological outcome in the pT2,R1 situation. On the other hand the side effects profile, with a potentially negative influence of postoperative continence and various delayed toxicities, is not insignificant despite modern radiation techniques and in the era of ultrasensitive PSA analysis should be considered in the risk-benefit assessment. As long as the optimal initiation of postoperative radiation therapy is unclear, the assessment of indications for adjuvant or salvage radiation for organ-limited prostate cancer with positive resection margins should be made after an individual patient consultation and under consideration of the recurrence risk factors, such as the Gleason grade and the localization and extent of the resection margins.

[Soft tissue sarcoma of the upper extremities. Analysis of factors relevant for prognosis in 160 patients].

PubMed

Lehnhardt, M; Hirche, C; Daigeler, A; Goertz, O; Ring, A; Hirsch, T; Drücke, D; Hauser, J; Steinau, H U

2012-02-01

Soft tissue sarcomas (STS) are a rare entity with reduced prognosis due to their aggressive biology. For an optimal treatment of STS identification of independent prognostic factors is crucial in order to reduce tumor-related mortality and recurrence rates. The surgical oncological concept includes wide excisions with resection safety margins >1 cm which enables acceptable functional results and reduced rates of amputation of the lower extremities. In contrast, individual anatomy of the upper extremities, in particular of the hand, leads to an intentional reduction of resection margins in order to preserve the extremity and its function with the main intention of tumor-free resection margins. In this study, the oncological safety and outcome as well as functional results were validated by a retrospective analysis of survival rate, recurrence rate and potential prognostic factors. A total of 160 patients who had been treated for STS of the upper extremities were retrospectively included. Independent prognostic factors were analyzed (primary versus recurrent tumor, tumor size, resection status, grade of malignancy, additional therapy, localization in the upper extremity). Kaplan-Meier analyses for survival rate and local control were calculated. Further outcome measures were functional results validated by the DASH score and rate of amputation. In 130 patients (81%) wide tumor excision (R0) was performed and in 19 patients (12%) an amputation was necessary. The 5-year overall survival rate was 70% and the 5-year survival rate in primary tumors was 81% whereas in recurrences 55% relapsed locally. The 10-year overall survival rate was 45% and the 5-year recurrence rate was 18% for primary STS and 43% for recurrent STS. Variance analysis revealed primary versus recurrent tumor, tumor size, resection status and grade of malignancy as independent prognostic factors. Analysis of functional results showed a median DASH score of 37 (0-100; 0=contralateral extremity). The 5-year survival and local recurrence rates are comparable to STS wide resections with safety margins >1 cm for the lower extremities and the trunk. Analysis of prognostic factors revealed resection status and the tumor-free resection margins to be the main goals in STS resection of upper extremity.

Assessment of immunogenicity and safety following primary and booster immunisation with a CRM197 -conjugated Haemophilus influenzae type B vaccine in healthy Chinese infants.

PubMed

Jun, L; Yuguo, C; Zhiguo, W; Jinfeng, L; Huawei, M; Xiuhua, L; Yonggui, Z; Yanhua, X; Kong, Y; Hongtao, L; Yuliang, Z

2013-10-01

Invasive meningitis and pneumonia caused by Haemophilus influenzae type b (Hib) is an important cause of childhood mortality in countries where Hib vaccination is not routine. We evaluated the non-inferiority of a licensed Hib vaccine, PRP-CRM(197) compared with a second licensed Hib vaccine, PRP-T, following the recommended Chinese immunisation schedule for infants between 6 months and 1 year of age. In the first study phase, 6-12 month-old infants received two primary doses of either PRP-CRM(197) (n = 335) or PRP-T (n = 335) vaccine administered 1 month apart. In the second study phase 8 months later, the same children received a single booster dose of vaccine identical to that use for priming (PRP-CRM(197), n = 327; PRP-T, n = 333). Serum levels of anti-polyribosylribitol phosphate (PRP) antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Non-inferiority of primary and booster doses was assessed in terms of percentages of subjects with anti-PRP antibody levels associated with providing short-term (≥ 0.15 μg/ml) and long-term (≥ 1.0 μg/ml) protection; the non-inferiority margin was set at -5%. PRP-CRM(197) was demonstrated to be non-inferior to PRP-T. Anti-PRP antibodies levels ≥ 0.15 μg/ml and ≥ 1.0 μg/ml were achieved by 97% of infants in the PRP-CRM(197) group and 98% of infants in the PRP-T group 1 month after primary immunisation, and by all subjects (100%) in both vaccine groups 1 month after booster administration. Safety profiles for both vaccines were similar; no serious adverse events, deaths or adverse events leading to withdrawal occurred during the study. PRP-CRM(197) was well-tolerated and immunologically non-inferior to a licensed comparator Hib vaccine in Chinese infants (Clinicaltrials.gov: NCT01044316 & NCT01226953). © 2013 John Wiley & Sons Ltd.

Transhepatic Hilar Approach for Perihilar Cholangiocarcinoma: Significance of Early Judgment of Resectability and Safe Vascular Reconstruction.

PubMed

Kuriyama, Naohisa; Isaji, Shuji; Tanemura, Akihiro; Iizawa, Yusuke; Kato, Hiroyuki; Murata, Yasuhiro; Azumi, Yoshinori; Kishiwada, Masashi; Mizuno, Shugo; Usui, Masanobu; Sakurai, Hiroyuki

2017-03-01

In the most common surgical procedure for perihilar cholangiocarcinoma, the margin status of the proximal bile duct is determined at the final step. Our procedure, the transhepatic hilar approach, confirms a cancer-negative margin status of the proximal bile duct first. We first performed a partial hepatic parenchymal transection to expose the hilar plate, and then transected the proximal bile duct to confirm margin status. Then, divisions of the hepatic artery and portal vein of the future resected liver are performed, followed by the residual hepatic parenchymal transection. The transhepatic hilar approach offers a wide surgical field for safe resection and reconstruction of the portal vein in the middle of the hepatectomy. We reviewed 23 patients with perihilar cholangiocarcinoma who underwent major hepatectomy using our procedure from 2011 to 2015. A combined vascular resection and reconstruction was carried out in 14 patients (60.9%). R0 resection was achieved in 17 patients (73.9%), and the overall 3-year survival rate was 52.9% (median survival time 52.4 months). The transhepatic hilar approach is useful and practicable regardless of local tumor extension, enabling us to determine tumor resectability and perform safe resection and reconstruction of the portal vein early in the operation.

Limited resection for duodenal gastrointestinal stromal tumors: Surgical management and clinical outcome

PubMed Central

Hoeppner, Jens; Kulemann, Birte; Marjanovic, Goran; Bronsert, Peter; Hopt, Ulrich Theodor

2013-01-01

AIM: To analyze our experience in patients with duodenal gastrointestinal stromal tumors (GIST) and review the appropriate surgical approach. METHODS: We retrospectively reviewed the medical records of all patients with duodenal GIST surgically treated at our medical institution between 2002 and 2011. Patient files, operative reports, radiological charts and pathology were analyzed. For surgical therapy open and laparoscopic wedge resections and segmental resections were performed for limited resection (LR). For extended resection pancreatoduodenectomy was performed. Age, gender, clinical symptoms of the tumor, anatomical localization, tumor size, mitotic count, type of resection resectional status, neoadjuvant therapy, adjuvant therapy, risk classification and follow-up details were investigated in this retrospective study. RESULTS: Nine patients (5 males/4 females) with a median age of 58 years were surgically treated. The median follow-up period was 45 mo (range 6-111 mo). The initial symptom in 6 of 9 patients was gastrointestinal bleeding (67%). Tumors were found in all four parts of the duodenum, but were predominantly located in the first and second part of the duodenum with each 3 of 9 patients (33%). Two patients received neoadjuvant medical treatment with 400 mg imatinib per day for 12 wk before resection. In one patient, the GIST resection was done by pancreatoduodenectomy. The 8 LRs included a segmental resection of pars 4 of the duodenum, 5 wedge resections with primary closure and a wedge resection with luminal closure by Roux-Y duodeno-jejunostomy. One of these LRs was done minimally invasive; seven were done in open fashion. The median diameter of the tumors was 54 mm (14-110 mm). Using the Fletcher classification scheme, 3/9 (33%) tumors had high risk, 1/9 (11%) had intermediate risk, 4/9 (44%) had low risk, and 1/9 (11%) had very low risk for aggressive behaviour. Seven resections showed microscopically negative transsection margins (R0), two showed positive margins (R1). No patient developed local recurrence during follow-up. The one patient who underwent pancreatoduodenectomy died due to progressive disease with hepatic metastasis but without evidence of local recurrence. Another patient died in complete remission due to cardiac disease. Seven of the nine patients are alive disease-free. CONCLUSION: In patients with duodenal GIST, limited surgical resection with microscopically negative margins, but also with microscopically positive margins, lead to very good local and systemic disease-free survival. PMID:23515427

Initial Experience With rhBMP-2 Delivered in a Compressive Resistant Matrix for Mandibular Reconstruction in 5 Dogs.

PubMed

Boudrieau, Randy J

2015-05-01

To document cumulative initial experience and long-term follow-up of the use of rhBMP-2/CRM for reconstruction of large mandibular defects (≥5 cm) in dogs. Retrospective case series. Dogs (n = 5). Medical records (October 1999-April 2011) of dogs that had mandibular reconstruction for defects/resections of ≥5 cm using rhBMP-2/CRM were reviewed. Signalment, preoperative assessment/rationale for mandibular reconstruction, surgical methods, postoperative assessment of the reconstruction (evaluation of occlusion), and complications were recorded. A definitive histologic diagnosis was obtained in dogs that had mandibular resection for mass removal. Long-term complications were determined. A minimum time frame of 2-year in-hospital follow-up was required for case inclusion. Mandibular reconstruction was successfully performed in all dogs' defects where gaps of 5-9 cm were bridged. Surgical reconstruction rapidly restored cosmetic appearance and function. All dogs healed with new bone formation across the gap. New bone formation was present within the defects as early as 2 weeks after surgery based on palpation, and new bone formation bridging the gap was documented radiographically by 16 weeks. Minor complications occurred in all dogs in the early postoperative period, and included early firm swelling and gingival dehiscence in 1 dog; late plate exposure in 3 dogs; and exuberant/cystic bone formation in 2 dogs (related to concentration/formulation of rhBMP-2/CRM). Two dogs had minor long-term complications of late plate exposure and a non-vital canine tooth; the plates and the affected canine tooth were removed. Long-term in-hospital follow-up was 5.3 years (range, 2-12.5 years); further long-term telephone follow-up was 6.3 years (range, 2-12.5 years). All owners were pleased with the outcome and would repeat the surgery again under similar circumstances. The efficacy and success of this mandibular reconstruction technique, using rhBMP-2/CRM with plate fixation, was demonstrated with bridging of large mandibular defects regardless of the underlying cause, and with excellent cosmetic and functional results. Complications were common, but considered minor and easily treated. The complications encountered revealed the importance of tailoring the use of BMPs and fixation methods to this specific anatomic location and indication. © Copyright 2014 by The American College of Veterinary Surgeons.

Liver tumor boundaries identified intraoperatively using real-time indocyanine green fluorescence imaging.

PubMed

Zhang, Ya-Min; Shi, Rui; Hou, Jian-Cun; Liu, Zi-Rong; Cui, Zi-Lin; Li, Yang; Wu, Di; Shi, Yuan; Shen, Zhong-Yang

2017-01-01

Clear delineation between tumors and normal tissues is ideal for real-time surgical navigation imaging. We investigated applying indocyanine green (ICG) fluorescence imaging navigation using an intraoperative administration method in liver resection. Fifty patients who underwent liver resection were divided into two groups based on clinical situation and operative purpose. In group I, sizes of superficial liver tumors were determined; tiny tumors were identified. In group II, the liver resection margin was determined; real-time navigation was performed. ICG was injected intravenously at the beginning of the operation; the liver surface was observed with a photodynamic eye (PDE). Liver resection margins were determined using PDE. Fluorescence contrast between normal liver and tumor tissues was obvious in 32 of 35 patients. A boundary for half the liver or specific liver segments was determined in nine patients by examining the portal vein anatomy after ICG injection. Eight small tumors not observed preoperatively were detected; the smallest was 2 mm. ICG fluorescence imaging navigation is a promising, simple, and safe tool for routine real-time intraoperative imaging during hepatic resection and clinical exploration in hepatocellular carcinoma, enabling high sensibility for identifying liver resection margins and detecting tiny superficial tumors.

Impact of Resection Margin Distance on Survival of Pancreatic Cancer: A Systematic Review and Meta-Analysis

PubMed Central

Kim, Kyung Su; Kwon, Jeanny; Kim, Kyubo; Chie, Eui Kyu

2017-01-01

Purpose While curative resection is the only chance of cure in pancreatic cancer, controversies exist about the impact of surgical margin status on survival. Non-standardized pathologic report and different criteria on the R1 status made it difficult to implicate adjuvant therapy after resection based on the margin status. We evaluated the influence of resection margins on survival by meta-analysis. Materials and Methods We thoroughly searched electronic databases of PubMed, EMBASE, and Cochrane Library. We included studies reporting survival outcomes with different margin status: involved margin (R0 mm), margin clearance with ≤ 1 mm (R0-1 mm), and margin with > 1 mm (R>1 mm). Hazard ratio (HR) for overall survival was extracted, and a random-effects model was used for pooled analysis. Results A total of eight retrospective studies involving 1,932 patients were included. Pooled HR for overall survival showed that patients with R>1 mm had reduced risk of death than those with R0-1 mm (HR, 0.74; 95% confidence interval [CI], 0.61 to 0.88; p=0.001). In addition, patients with R0-1 mm had reduced risk of death than those with R0 mm (HR, 0.81; 95% CI, 0.72 to 0.91; p < 0.001). There was no heterogeneity between the included studies (I2 index, 42% and 0%; p=0.10 and p=0.82, respectively). Conclusion Our results suggest that stratification of the patients based on margin status is warranted in the clinical trials assessing the role of adjuvant treatment for pancreatic cancer. PMID:27561314

Role of imprint/exfoliative cytology in ulcerated skin neoplasms.

PubMed

Ramakrishnaiah, Vishnu Prasad Nelamangala; Babu, Ravindra; Pai, Dinker; Verma, Surendra Kumar

2013-12-01

Imprint cytology is a method of studying cells by taking an imprint from the cut surface of a wedge biopsy specimen or from the resected margins of a surgical specimen. It is rapid, simple and fairly accurate. Exfoliative cytology is an offshoot from the imprint cytology where in cells obtained from the surface of ulcers, either by scrape or brush, are analyzed for the presence of malignant cells. We undertook this study to see the role of imprint/exfoliative cytology in the diagnosis of ulcerated skin neoplasm and to check the adequacy of resected margins intra-operatively. This was a prospective investigative study conducted from September 2003 to July 2005. All patients presenting to surgical clinic with ulcerated skin and soft tissue tumours were included in the study. A wedge biopsy obtained from the ulcer and imprint smears were taken from the cut surface. Exfoliative cytology was analyzed from the surface smears. Wedge biopsy specimen was sent for histopathological (HPE) examination. The cytology and HPE were analyzed by a separate pathologist. Imprint cytology was also used to check the adequacy of resected margins in case of wide excision. This was compared with final HPE. Total of 107 patients was included in the present study and 474 imprint smears were done, with an average of 4.43 slides per lesion. Out of 59 wide excision samples, 132 imprint smears were prepared for assessing resected margins accounting for an average of 2.24 slides per each excised lesion. On combining imprint cytology with exfoliative cytology the overall sensitivity, specificity and positive predictive value were 90.38 %, 100 % and 90.38 % respectively. Only one out of 59 cases had a positive resected margin which was not picked by imprint cytology. Imprint cytology can be used for rapid and accurate diagnosis of various skin malignancies. It can also be used to check the adequacy of the resected margin intraoperatively.

Tumor resection at the pelvis using three-dimensional planning and patient-specific instruments: a case series.

PubMed

Jentzsch, Thorsten; Vlachopoulos, Lazaros; Fürnstahl, Philipp; Müller, Daniel A; Fuchs, Bruno

2016-09-21

Sarcomas are associated with a relatively high local recurrence rate of around 30 % in the pelvis. Inadequate surgical margins are the most important reason. However, obtaining adequate margins is particularly difficult in this anatomically demanding region. Recently, three-dimensional (3-D) planning, printed models, and patient-specific instruments (PSI) with cutting blocks have been introduced to improve the precision during surgical tumor resection. This case series illustrates these modern 3-D tools in pelvic tumor surgery. The first consecutive patients with 3-D-planned tumor resection around the pelvis were included in this retrospective study at a University Hospital in 2015. Detailed information about the clinical presentation, imaging techniques, preoperative planning, intraoperative surgical procedures, and postoperative evaluation is provided for each case. The primary outcome was tumor-free resection margins as assessed by a postoperative computed tomography (CT) scan of the specimen. The secondary outcomes were precision of preoperative planning and complications. Four patients with pelvic sarcomas were included in this study. The mean follow-up was 7.8 (range, 6.0-9.0) months. The combined use of preoperative planning with 3-D techniques, 3-D-printed models, and PSI for osteotomies led to higher precision (maximal (max) error of 0.4 centimeters (cm)) than conventional 3-D planning and freehand osteotomies (max error of 2.8 cm). Tumor-free margins were obtained where measurable (n = 3; margins were not assessable in a patient with curettage). Two insufficiency fractures were noted postoperatively. Three-dimensional planning as well as the intraoperative use of 3-D-printed models and PSI are valuable for complex sarcoma resection at the pelvis. Three-dimensionally printed models of the patient anatomy may help visualization and precision. PSI with cutting blocks help perform very precise osteotomies for adequate resection margins.

Is computer navigation when used in the surgery of iliosacral pelvic bone tumours safer for the patient?

PubMed

Laitinen, M K; Parry, M C; Albergo, J I; Grimer, R J; Jeys, L M

2017-02-01

Due to the complex anatomy of the pelvis, limb-sparing resections of pelvic tumours achieving adequate surgical margins, can often be difficult. The advent of computer navigation has improved the precision of resection of these lesions, though there is little evidence comparing resection with or without the assistance of navigation. Our aim was to evaluate the efficacy of navigation-assisted surgery for the resection of pelvic bone tumours involving the posterior ilium and sacrum. Using our prospectively updated institutional database, we conducted a retrospective case control study of 21 patients who underwent resection of the posterior ilium and sacrum, for the treatment of a primary sarcoma of bone, between 1987 and 2015. The resection was performed with the assistance of navigation in nine patients and without navigation in 12. We assessed the accuracy of navigation-assisted surgery, as defined by the surgical margin and how this affects the rate of local recurrence, the disease-free survival and the effects on peri-and post-operative morbidity. The mean age of the patients was 36.4 years (15 to 66). The mean size of the tumour was 10.9 cm. In the navigation-assisted group, the margin was wide in two patients (16.7%), marginal in six (66.7%) and wide-contaminated in one (11.1%) with no intralesional margin. In the non-navigated-assisted group; the margin was wide in two patients (16.7%), marginal in five (41.7%), intralesional in three (25.0%) and wide-contaminated in two (16.7%). Local recurrence occurred in two patients in the navigation-assisted group (22.2%) and six in the non-navigation-assisted group (50.0%). The disease-free survival was significantly better when operated with navigation-assistance (p = 0.048). The blood loss and operating time were less in the navigated-assisted group, as was the risk of a foot drop post-operatively. The introduction of navigation-assisted surgery for the resection of tumours of the posterior ilium and sacrum has increased the safety for the patients and allows for a better oncological outcome. Cite this article: Bone Joint J 2017;99-B:261-6. ©2017 The British Editorial Society of Bone & Joint Surgery.

Ultrasound-guided breast-sparing surgery to improve cosmetic outcomes and quality of life. A prospective multicentre randomised controlled clinical trial comparing ultrasound-guided surgery to traditional palpation-guided surgery (COBALT trial)

PubMed Central

2011-01-01

Background Breast-conserving surgery for breast cancer was developed as a method to preserve healthy breast tissue, thereby improving cosmetic outcomes. Thus far, the primary aim of breast-conserving surgery has been the achievement of tumour-free resection margins and prevention of local recurrence, whereas the cosmetic outcome has been considered less important. Large studies have reported poor cosmetic outcomes in 20-40% of patients after breast-conserving surgery, with the volume of the resected breast tissue being the major determinant. There is clear evidence for the efficacy of ultrasonography in the resection of nonpalpable tumours. Surgical resection of palpable breast cancer is performed with guidance by intra-operative palpation. These palpation-guided excisions often result in an unnecessarily wide resection of adjacent healthy breast tissue, while the rate of tumour-involved resection margins is still high. It is hypothesised that the use of intra-operative ultrasonography in the excision of palpable breast cancer will improve the ability to spare healthy breast tissue while maintaining or even improving the oncological margin status. The aim of this study is to compare ultrasound-guided surgery for palpable tumours with the standard palpation-guided surgery in terms of the extent of healthy breast tissue resection, the percentage of tumour-free margins, cosmetic outcomes and quality of life. Methods/design In this prospective multicentre randomised controlled clinical trial, 120 women who have been diagnosed with palpable early-stage (T1-2N0-1) primary invasive breast cancer and deemed suitable for breast-conserving surgery will be randomised between ultrasound-guided surgery and palpation-guided surgery. With this sample size, an expected 20% reduction of resected breast tissue and an 18% difference in tumour-free margins can be detected with a power of 80%. Secondary endpoints include cosmetic outcomes and quality of life. The rationale, study design and planned analyses are described. Conclusion The COBALT trial is a prospective, multicentre, randomised controlled study to assess the efficacy of ultrasound-guided breast-conserving surgery in patients with palpable early-stage primary invasive breast cancer in terms of the sparing of breast tissue, oncological margin status, cosmetic outcomes and quality of life. Trial Registration Number Netherlands Trial Register (NTR): NTR2579 PMID:21410949

Challenges of local recurrence and cure in low grade malignant tumors of the spine.

PubMed

Boriani, Stefano; Saravanja, Davor; Yamada, Yoshiya; Varga, Peter Pal; Biagini, Roberto; Fisher, Charles G

2009-10-15

Systematic review and ambispective multicenter cohort study. 1. To compare the effects of wide/marginal (en bloc) resection with intralesional resection on local recurrence and survival for chordomas and chondrosarcomas of the spine. 2. To determine the influence of radiation therapy in the management of chordomas and chondrosarcomas. Chordomas and chondrosarcomas of the spine are prone to local recurrence and death despite being low-grade malignant tumors. No study to date has enough numbers or adequate scientific rigor to determine the influence of resection or radiation therapy on outcome. A systematic review was performed to evaluate the 2 objectives. In addition an ambispective multicenter cohort analysis of chordomas and chondrosarcomas was performed. The GRADE system of analysis integrating the results of the systematic review, the multicenter cohort study and the expert opinion of the Spine Oncology Study Group (SOSG) was used to arrive at treatment recommendations. A total of 63 articles were included in the systematic reviews. Evidence was low quality. En bloc resection appeared to improve both local recurrence and disease free survival in Chordoma and Chondrosarcoma. Radiation therapy had a positive impact on the management of Chordoma and Chondrosarcoma with predictably low side effects. The cohort analysis showed significantly decreased local recurrence for Chordoma (P < 0.0001) and Chondrosarcoma (P < 0.0001) with en bloc resection, and significantly decreased death for both Chordoma (P = 0.0001) and Chondrosarcoma (P = 0.0015) with en bloc resection. When wide or marginal margins (en bloc) are achieved in surgical resection of chordomas and chondrosarcomas of the spine there is a decrease in local recurrence and mortality. Therefore, en bloc resection should be undertaken for the treatment of chordomas and chondrosarcomas of the spine. Strong Recommendation, Moderate Quality Evidence.Radiation therapy of at least 60 to 65 Gy equivalents is indicated as an adjuvant treatment for chordoma and chondrosarcoma of the spine when there has been incomplete resection or an intralesional margin. Weak Recommendation, Low Quality Evidence.

Prevalence and predictive factors for the detection of carcinoma in cavity margin performed at the time of breast lumpectomy.

PubMed

Tengher-Barna, Iulia; Hequet, Delphine; Reboul-Marty, Jeanne; Frassati-Biaggi, Annonciade; Seince, Nathalie; Rodrigues-Faure, Anabela; Uzan, Michèle; Ziol, Marianne

2009-02-01

Margin resection status is a major risk factor for the development of local recurrence in breast conservation therapy for carcinoma. Tumor bed excision sent as separate orientated cavity margins represents a tool to verify the completeness of the carcinoma resection. We aimed to (1) determine the prevalence of positive cavity margin and its influence on subsequent surgical treatment and (2) identify potential predictive factors for positive cavity margins. From 2003 to 2006, 107 (57 years; 30-88) consecutive patients who underwent a lumpectomy for carcinoma with four orientated cavity margins for carcinoma were selected. Preoperative clinical, radiological and histological data, perioperative macroscopic characteristics and definitive histological analysis results were recorded. Lumpectomy or cavity margins were considered as positive when the distance from carcinoma to the margin was less than or equal to 3 mm. Histological examination of cavity margins showed carcinoma in 38 patients (35%), therefore modifying subsequent surgical therapy in 33 cases. Examination of the cavity margins led (1) to avoiding surgical re-excision in 20 cases (lumpectomy margins were positive and the cavity margins negative), (2) to performing a mastectomy or a re-excision in 13 cases (carcinoma was detected in the cavity margins although the lumpectomy margins were negative or tumor size was superior to 3 cm). Between preoperative and perioperative parameters, US scan and macroscopic size of the tumor were predictive factors for positive cavity margins whereas characteristics of the carcinoma determined on biopsy samples and macroscopic status of the lumpectomy margins were not. Our study confirms that the systematic practice of cavity margin resection avoids surgical re-excision and reduces the likelihood of underestimating the extent of the tumor.

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

A case of distal extrahepatic cholangiocarcinoma with two positive resection margins.

PubMed

Warner, Wayne A; Ramcharan, Wesley; Harnanan, Dave; Umakanthan, Srikanth; Maharaj, Ravi

2016-11-01

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.

Transoral robotic surgery for neurogenic tumors of the prestyloid parapharyngeal space.

PubMed

Lee, Hyoung Shin; Kim, Jinna; Lee, Hyun Jin; Koh, Yoon Woo; Choi, Eun Chang

2012-08-01

The parapharyngeal space is a difficult area for a surgical approach due to anatomical complexity. We performed a minimally invasive and precise surgical technique to remove neurogenic tumors of the prestyloid parapharyngeal space using transoral robotic instrumentation. The mass was successfully removed in the two cases with three-dimensional visualization providing an excellent view of the resection margin and the dissection plane preserving the vital structures. An adequate resection margin was acquired, and no violation of the tumor capsule occurred. No significant complications were noted. Transoral robotic surgery was feasible for neurogenic tumors of the prestyloid parapharyngeal space, providing a sufficient resection margin and delicate dissection through excellent surgical views and instrumentation. Copyright © 2012. Published by Elsevier Ireland Ltd.

Hilar cholangiocarcinoma: controversies on the extent of surgical resection aiming at cure.

PubMed

Xiang, Shuai; Lau, Wan Yee; Chen, Xiao-ping

2015-02-01

Hilar cholangiocarcinoma is the most common malignant tumor affecting the extrahepatic bile duct. Surgical treatment offers the only possibility of cure, and it requires removal of all tumoral tissues with adequate resection margins. The aims of this review are to summarize the findings and to discuss the controversies on the extent of surgical resection aiming at cure for hilar cholangiocarcinoma. The English medical literatures on hilar cholangiocarcinoma were studied to review on the relevance of adequate resection margins, routine caudate lobe resection, extent of liver resection, and combined vascular resection on perioperative and long-term survival outcomes of patients with resectable hilar cholangiocarcinoma. Complete resection of tumor represents the most important prognostic factor of long-term survival for hilar cholangiocarcinoma. The primary aim of surgery is to achieve R0 resection. When R1 resection is shown intraoperatively, further resection is recommended. Combined hepatic resection is now generally accepted as a standard procedure even for Bismuth type I/II tumors. Routine caudate lobe resection is also advocated for cure. The extent of hepatic resection remains controversial. Most surgeons recommend major hepatic resection. However, minor hepatic resection has also been advocated in most patients. The decision to carry out right- or left-sided hepatectomy is made according to the predominant site of the lesion. Portal vein resection should be considered when its involvement by tumor is suspected. The curative treatment of hilar cholangiocarcinoma remains challenging. Advances in hepatobiliary techniques have improved the perioperative and long-term survival outcomes of this tumor.

Whipple Resection: Concordance Between Frozen Section And Permanent Section Diagnosis Of Surgical Margins.

PubMed

Bilal, Muhammad; Tariq, Hina; Mamoon, Nadira

2018-01-01

Margin assessment is done in Whipple procedures which are usually performed to resect tumours of head of pancreas and ampullary/periampullary region. Aims and objective of the study are to determine the concordance between frozen sections (FS) and permanent sections (PS) of surgical margins in Whipple resections. It is a retrospective study, from January 2008 to January 2015 (07 years). It includes the specimen with malignancy in final report and for which FS of pancreatic and/or CBD margin(s) were requested. Data was retrieved from Laboratory information system (LIS) database. Of the 41 bile duct margins in cases of ampullary tumours, 03 were positive on FS as well as PS, 35 were negative on FS as well as on PS. Results showed 100% sensitivity, 92.1% specificity, 50% PPV and 100% NPV. Results of 36 pancreatic margins in cases of ampullary showed 100% sensitivity, 97.1% specificity, 50% PPV and 100% NPV. In pancreatic carcinoma cases, none of CBD margins were reported as positive on FS, 02 margins reported as negative were found positive on PS, while 17 were negative on FS as well as PS. Results showed 100% specificity and 89.5% NPV. Of the 27 pancreatic margins tested in pancreatic tumours 100% sensitivity, 94.1% specificity, 88.9% PPV and 100% NPV was found. Factors such as absent prior tissue diagnosis and/or inflammatory processes make margin diagnosis difficult. However, a high concordance was observed between our FS and PS diagnosis.

Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node Positivity.

PubMed

Gao, Sarah J; Park, Henry S; Corso, Christopher D; Rutter, Charles E; Kim, Anthony W; Johung, Kimberly L

2017-07-01

The optimal adjuvant treatment for cT1-2 N0 esophageal cancer patients found to have pathologic nodal involvement after an upfront operation is unclear. This study investigated the effects of postoperative chemotherapy and chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental pN + disease stratified by margin status. We identified cT1-2 N0 M0 esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data Base. Patients were categorized as having received surgical resection alone, surgical resection followed by chemotherapy (S+CT), and surgical resection followed by concurrent chemoradiation therapy (S+CRT). Subset analyses were conducted on margin-negative and margin-positive patients. Overall survival was compared by Kaplan-Meier estimation, the log-rank test, and multivariable Cox regression analysis. Among 443 patients, 52.6% received surgical resection alone, 18.7% received S+CT, and 28.6% received S+CRT. Significantly more adenocarcinoma patients received adjuvant treatment (50.8%) than squamous cell carcinoma patients (27.7%, p = 0.001). On multivariable analysis, S+CT (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; p = 0.014) and S+CRT (hazard ratio, 0.73; 95% confidence interval,. 0.55 to 0.98; p = 0.038) both were associated with significantly increased overall survival. These findings persisted among margin-negative patients. However, in margin-positive patients, S+CRT (hazard ratio, 0.29; p = 0.002) was the only treatment arm that was associated with significantly improved survival compared with surgical resection alone. Among cT1-2 N0 pN + esophageal cancer patients, adjuvant chemotherapy may be sufficient for margin-negative patients, whereas adjuvant chemoradiation therapy appears necessary for margin-positive patients. Further prospective studies are needed to confirm the results. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Early Stage olfactory neuroblastoma and the impact of resecting dura and olfactory bulb.

PubMed

Mays, Ashley C; Bell, Diana; Ferrarotto, Renata; Phan, Jack; Roberts, Dianna; Fuller, Clifton D; Frank, Steven J; Raza, Shaan M; Kupferman, Michael E; DeMonte, Franco; Hanna, Ehab Y; Su, Shirley Y

2018-06-01

Compare outcomes of patients with olfactory neuroblastoma (ONB) without skull base involvement treated with and without resection of the dura and olfactory bulb. Retrospective review of ONB patients treated from 1992 to 2013 at the MD Anderson Cancer Center (The University of Texas, Houston, Texas, U.S.A.). Primary outcomes were overall and disease-free survival. Thirty-five patients were identified. Most patients had Kadish A/B. tumors (97%), Hyams grade 2 (70%), with unilateral involvement (91%), and arising from the nasal cavity (68%). Tumor involved the mucosa abutting the skull base in 42% of patients. Twenty-five patients (71%) received surgery and radiation, whereas the remainder had surgery alone. Five patients (14%) had bony skull base resection, and eight patients (23%) had resection of bony skull base, dura, and olfactory bulb. Surgical margins were grossly positive in one patient (3%) and microscopically positive in four patients (12%). The 5- and 10-year overall survival were 93% and 81%, respectively. The 5- and 10-year disease-free survival (DFS) were 89% and 78%, respectively. Bony cribriform plate resection was associated with better DFS (P = 0.05), but dura and olfactory bulb resection was not (P = 0.11). There was a trend toward improved DFS in patients with negative resection margins (P = 0.19). Surgical modality (open vs. endoscopic) and postoperative radiotherapy did not impact DFS. Most Kadish A/B ONB tumors have low Hyams grade, unilateral involvement, and favorable survival outcomes. Resection of the dura and olfactory bulb is not oncologically advantageous in patients without skull base involvement who are surgically treated with negative resection margins and cribriform resection. 4. Laryngoscope, 128:1274-1280, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Significance of R1 Resection for Advanced Colorectal Liver Metastases in the Era of Modern Effective Chemotherapy.

PubMed

Laurent, Christophe; Adam, Jean-Philippe; Denost, Quentin; Smith, Denis; Saric, Jean; Chiche, Laurence

2016-05-01

The prognosis impact of positive margins after resection of colorectal liver metastases (CLM) in patients treated with modern effective chemotherapy has not been elucidated. The objective was to compare oncologic outcomes after R0 and R1 resections in the era of modern effective chemotherapy. Between 1999 and 2010, all consecutive patients undergoing liver resection for CLM were analyzed retrospectively. Patients with extrahepatic metastases, macroscopic residual tumor, treated with combined radiofrequency, or not treated with chemotherapy were excluded. Survival and recurrence after R0 (tumor-free margin >0 mm) and R1 resections were analyzed. Among 466 patients undergoing hepatectomy for CLM, 191 were eligible. Of them, 164 (86 %) received preoperative chemotherapy and 105 (55 %) received postoperative chemotherapy. R1 resection (10 %) was comparable in patients treated or not by preoperative chemotherapy. R1 status was associated with more intrahepatic recurrences. Overall survival (OS) (44 vs. 61 %; p = 0.047) and disease-free survival (DFS) (8 vs. 26 %; p = 0.082) were lower in patients after R1 compared to R0 resection (32 months of median follow-up). Preoperative chemotherapy and major hepatectomy were prognostic factors of survival, whereas postoperative chemotherapy was a protective factor from recurrences. In patients treated with preoperative chemotherapy, OS and DFS were similar between R1 and R0 resections (40 vs. 55 %, p = 0.104 and 9 vs. 22 %, p = 0.174, respectively). In the era of modern effective chemotherapy, R1 resection leads to more intrahepatic recurrences but did not affect OS in selected patient responders to neoadjuvant chemotherapy. Postoperative chemotherapy protects from recurrences whatever the margin resection status.

Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological Outcomes in Rectal Cancer: The ALaCaRT Randomized Clinical Trial.

PubMed

Stevenson, Andrew R L; Solomon, Michael J; Lumley, John W; Hewett, Peter; Clouston, Andrew D; Gebski, Val J; Davies, Lucy; Wilson, Kate; Hague, Wendy; Simes, John

2015-10-06

Laparoscopic procedures are generally thought to have better outcomes than open procedures. Because of anatomical constraints, laparoscopic rectal resection may not be better because of limitations in performing an adequate cancer resection. To determine whether laparoscopic resection is noninferior to open rectal cancer resection for adequacy of cancer clearance. Randomized, noninferiority, phase 3 trial (Australasian Laparoscopic Cancer of the Rectum; ALaCaRT) conducted between March 2010 and November 2014. Twenty-six accredited surgeons from 24 sites in Australia and New Zealand randomized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge. Open laparotomy and rectal resection (n = 237) or laparoscopic rectal resection (n = 238). The primary end point was a composite of oncological factors indicating an adequate surgical resection, with a noninferiority boundary of Δ = -8%. Successful resection was defined as meeting all the following criteria: (1) complete total mesorectal excision, (2) a clear circumferential margin (≥1 mm), and (3) a clear distal resection margin (≥1 mm). Pathologists used standardized reporting and were blinded to the method of surgery. A successful resection was achieved in 194 patients (82%) in the laparoscopic surgery group and 208 patients (89%) in the open surgery group (risk difference of -7.0% [95% CI, -12.4% to ∞]; P = .38 for noninferiority). The circumferential resection margin was clear in 222 patients (93%) in the laparoscopic surgery group and in 228 patients (97%) in the open surgery group (risk difference of -3.7% [95% CI, -7.6% to 0.1%]; P = .06), the distal margin was clear in 236 patients (99%) in the laparoscopic surgery group and in 234 patients (99%) in the open surgery group (risk difference of -0.4% [95% CI, -1.8% to 1.0%]; P = .67), and total mesorectal excision was complete in 206 patients (87%) in the laparoscopic surgery group and 216 patients (92%) in the open surgery group (risk difference of -5.4% [95% CI, -10.9% to 0.2%]; P = .06). The conversion rate from laparoscopic to open surgery was 9%. Among patients with T1-T3 rectal tumors, noninferiority of laparoscopic surgery compared with open surgery for successful resection was not established. Although the overall quality of surgery was high, these findings do not provide sufficient evidence for the routine use of laparoscopic surgery. Longer follow-up of recurrence and survival is currently being acquired. anzctr.org Identifier: ACTRN12609000663257.

Determinants of survival after liver resection for metastatic colorectal carcinoma.

PubMed

Parau, Angela; Todor, Nicolae; Vlad, Liviu

2015-01-01

Prognostic factors for survival after liver resection for metastatic colorectal cancer identified up to date are quite inconsistent with a great inter-study variability. In this study we aimed to identify predictors of outcome in our patient population. A series of 70 consecutive patients from the oncological hepatobiliary database, who had undergone curative hepatic surgical resection for hepatic metastases of colorectal origin, operated between 2006 and 2011, were identified. At 44.6 months (range 13.7-73), 30 of 70 patients (42.85%) were alive. Patient demographics, primary tumor and liver tumor factors, operative factors, pathologic findings, recurrence patterns, disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were analyzed. Clinicopathologic variables were tested using univariate and multivariate analyses. The 3-year CSS after first hepatic resection was 54%. Median CSS survival after first hepatic resection was 40.2 months. Median CSS after second hepatic resection was 24.2 months. The 3-year DFS after first hepatic resection was 14%. Median disease free survival after first hepatic resection was 18 months. The 3-year DFS after second hepatic resection was 27% and median DFS after second hepatic resection 12 months. The 30-day mortality and morbidity rate after first hepatic resection was 5.71% and 12.78%, respectively. In univariate analysis CSS was significantly reduced for the following factors: age >53 years, advanced T stage of primary tumor, moderately- poorly differentiated tumor, positive and narrow resection margin, preoperative CEA level >30 ng/ml, DFS <18 months. Perioperative chemotherapy related to metastasectomy showed a trend in improving CSS (p=0.07). Perioperative chemotherapy improved DFS in a statistically significant way (p=0.03). Perioperative chemotherapy and achievement of resection margins beyond 1 mm were the major determinants of both CSS and DFS after first liver resection in multivariate analysis. In our series predictors of outcome in multivariate analysis were resection margins beyond 1mm and perioperative chemotherapy. Studies on larger population and analyses of additional clinicopathologic factors like genetic markers could contribute to development of clinical scoring models to assess the risk of relapse and survival.

Evaluation of margins in head and neck squamous cell carcinoma from the surgeon's perspective.

PubMed

Baumeister, Philipp; Baumüller, Konstantin; Harréus, Ulrich; Reiter, Maximilian; Welz, Christian

2018-05-01

The surgeon's evaluation of resection status based on frozen section analysis during operation and pathological examination of resected specimens often differ. For this study, we recapitulated the surgeon's perspective during an operation, accordingly classified the evaluation of margins by the surgeon, and analyzed its impact on the outcome compared with the pathological results. This was a retrospective analysis. As data sources, paper-based and digital patient files, as well as the Munich Cancer Registry database were used. Three hundred ninety-six cases were included in this analysis. Only the evaluation of margins by the surgeon influenced local control, and the pathological results influenced disease-free survival (DFS). Surprisingly, margins of >5 mm of normal tissue to cancer growth led to local control and overall survival (OS) significantly worse than 1 to 5-mm resections. The evaluation of margins by the surgeon is of significant importance for local control and OS. It is largely based on frozen section analysis, which, therefore, should be used whenever possible. © 2018 Wiley Periodicals, Inc.

Principles of treatment for soft tissue sarcoma.

PubMed

Dernell, W S; Withrow, S J; Kuntz, C A; Powers, B E

1998-02-01

Soft tissue sarcomas (STS) are mesenchymal tumors arising from connective tissue elements and are grouped together based on a common biologic behavior. The most common histologic types include malignant peripheral nerve sheath tumors (schwannoma and neurofibrosarcoma) "hemangiopericytoma," fibrosarcoma, and malignant fibrous histiocytoma. These tumors are relatively slow growing yet locally invasive with a high rate of recurrence following conservative management. Appropriate preoperative planning and aggressive surgical resection often result in long-term remission or cure. Identification and evaluation of resection margins are paramount in appropriate case management. The addition of radiotherapy after surgical resection can aid in remission for incompletely resected masses. Systemic chemotherapy for STS should be considered for high-grade tumors with a moderate metastatic potential. Potential prognostic factors include grade, resection margins, size, location, histologic type, and previous treatment, with grade and margins being the most important. Tumor types classified as STS that differ slightly in their presentation or treatment, including synovial cell sarcoma, rhabdomyosarcoma, liposarcoma, and vaccine-associated STS in cats, are discussed. Soft tissue sarcomas can be a frustrating disease to treat, but adherence to solid surgical oncology principles can greatly increase the odds of good disease control.

Effectiveness of navigation-guided cyst aspiration before resection of large cystic brain tumors: a proof of concept for more radical surgery.

PubMed

Roh, Tae Hoon; Sung, Kyoung Su; Kang, Seok-Gu; Moon, Ju Hyung; Kim, Eui Hyun; Kim, Sun Ho; Chang, Jong Hee

2017-10-01

Resection of tumors close to the corticospinal tract (CST) carries a high risk of damage to the CST. For cystic tumors, aspirating the cyst before resection may reduce the risk of damage to vital structures. This study evaluated the effectiveness of cyst aspiration, by comparing the results before and after aspiration of diffusion tensor image (DTI) tractography. This study enrolled 23 patients with large cystic brain tumors (>20 cm 3 ) between 2012 and 2016. All underwent magnetic resonance imaging (MRI), including DTI tractography, followed by navigation-guided aspiration of the cyst and subsequent tumor resection via craniotomy. Distances between the tumor margin and CST before and after cyst aspiration, volume reduction, and postoperative outcomes were assessed. Median tumor volume decreased from 88 cm 3 (range, 25-153) to 29 cm 3 (range, 20-80) and distances between tumor margins and the CST increased from 5.7 mm (range, 0.6-22.0) to 14.8 mm (range, 0.6-41.4) after aspiration. Neurological symptoms of patients immediately improved after cyst aspiration. All patients, except for one with a secondary glioblastoma, underwent gross total resection of the tumor. No neurological deterioration was observed after tumor resection. Navigation-guided cyst aspiration followed by resection is a useful and safe procedure for brain tumors with large cystic components. Cyst aspiration resulted in expansion of the compressed brain tissue between the tumor margins and vital structures, making maximal safe resection possible.

Factors associated with a primary surgical approach for sinonasal squamous cell carcinoma.

PubMed

Cracchiolo, Jennifer R; Patel, Krupa; Migliacci, Jocelyn C; Morris, Luc T; Ganly, Ian; Roman, Benjamin R; McBride, Sean M; Tabar, Viviane S; Cohen, Marc A

2018-03-01

Primary surgery is the preferred treatment of T1-T4a sinonasal squamous cell carcinoma (SNSCC). Patients with SNSCC in the National Cancer Data Base (NCDB) were analyzed. Factors that contributed to selecting primary surgical treatment were examined. Overall survival (OS) in surgical patients was analyzed. Four-thousand seven hundred and seventy patients with SNSCC were included. In T1-T4a tumors, lymph node metastases, maxillary sinus location, and treatment at high-volume centers were associated with selecting primary surgery. When primary surgery was utilized, tumor factors and positive margin guided worse OS. Adjuvant therapy improved OS in positive margin resection and advanced T stage cases. Tumor and non-tumor factors are associated with selecting surgery for the treatment of SNSCC. When surgery is selected, tumor factors drive OS. Negative margin resection should be the goal of a primary surgical approach. When a positive margin resection ensues, adjuvant therapy may improve OS. © 2017 Wiley Periodicals, Inc.

Liver metastasis resection: a simple technique that makes it easier.

PubMed

de Santibañes, Eduardo; Sánchez Clariá, Rodrigo; Palavecino, Martín; Beskow, Axel; Pekolj, Juan

2007-09-01

Liver resection is the only therapeutic option that achieves long-term survival for patients with hepatic metastases. We propose a technique that causes traction and countertraction on the resection area, thus easily exposing the structures to be ligated. Because the parenchyma protrudes like a cork from a bottle, we named this procedure the "corkscrew technique". The objective of this work was to describe an original surgical technique to resect liver metastases. We delimit the resection area at 2 cm from the tumor. We place separated stitches, in a radiate way. The needle diameter must allow passing far from the deepest margin of the tumor. The stitches must be tractioned all together to separate the tumor from the normal parenchyma. Between the years 1983 and 2006, we perform 1,270 liver resections. We used the corkscrew technique-like procedure in only 612 patients, whereas in 129 patients, we associated it to an anatomic resection. Mortality was 1%. Morbidity was 16% with a reoperation rate of 3%. The corkscrew technique is simple and safe, spares surgical time, avoids blood loss, ensures free tumor margins, and is easy to perform.

Detection of tumor DNA at the margins of colorectal cancer liver metastasis

PubMed Central

Holdhoff, Matthias; Schmidt, Kerstin; Diehl, Frank; Aggrawal, Nishant; Angenendt, Philipp; Romans, Katharine; Edelstein, Daniel L.; Torbenson, Michael; Kinzler, Kenneth W.; Vogelstein, Bert; Choti, Michael A.; Diaz, Luis A.

2012-01-01

Purpose Defining an adequate resection margin of colorectal cancer liver metastases is essential for optimizing surgical technique. We have attempted to evaluate the resection margin through a combination of histopathologic and genetic analyses. Experimental Design We evaluated 88 samples of tumor margins from 12 patients with metastatic colon cancer who each underwent partial hepatectomy of one to six liver metastases. Punch biopsies of surrounding liver tissue were obtained at 4, 8, 12 and 16 mm from the tumor border. DNA from these biopsies was analyzed by a sensitive PCR-based technique, called BEAMing, for mutations of KRAS, PIK3CA, APC, or TP53 identified in the corresponding tumor. Results Mutations were identified in each patient’s resected tumor and used to analyze the 88 samples circumscribing the tumor-normal border. Tumor-specific mutant DNA was detectable in surrounding liver tissue in five of these 88 samples, all within 4 mm of the tumor border. Biopsies that were 8, 12, and 16 mm from the macroscopic visible margin were devoid of detectable mutant tumor DNA as well as of microscopically visible cancer cells. Tumors with a significant radiologic response to chemotherapy were not associated with any increase in mutant tumor DNA in beyond 4 mm of the main tumor. Conclusions Mutant tumor-specific DNA can be detected beyond the visible tumor margin, but never beyond 4 mm, even in patients whose tumors were larger prior to chemotherapy. These data provide a rational basis for determining the extent of surgical excision required in patients undergoing resection of liver metastases. PMID:21531819

Positive Margins by Oropharyngeal Subsite in Transoral Robotic Surgery for T1/T2 Squamous Cell Carcinoma.

PubMed

Persky, Michael J; Albergotti, William G; Rath, Tanya J; Kubik, Mark W; Abberbock, Shira; Geltzeiler, Mathew; Kim, Seungwon; Duvvuri, Umamaheswar; Ferris, Robert L

2018-04-01

Objective To compare positive margin rates between the 2 most common subsites of oropharyngeal transoral robotic surgery (TORS), the base of tongue (BOT) and the tonsil, as well as identify preoperative imaging characteristics that predispose toward positive margins. Study Design Case series with chart review. Setting Tertiary care referral center. Subjects and Methods We compared the final and intraoperative positive margin rate between TORS resections for tonsil and BOT oropharyngeal squamous cell carcinoma (OPSCC), as well as the effect of margins on treatment. A blinded neuroradiologist examined the preoperative imaging of BOT tumors to measure their dimensions and patterns of spread and provided a prediction of final margin results. Results Between January 2010 and May 2016, a total of 254 patients underwent TORS for OPSCC. A total of 140 patients who underwent TORS for T1/T2 OPSCC met inclusion criteria. A final positive margin is significantly more likely for BOT tumors than tonsil tumors (19.6% vs 4.5%, respectively, P = .004) and likewise for intraoperative margins of BOT and tonsil tumors (35.3% vs 12.4%, respectively; P = .002). A positive final margin is 10 times more likely to receive chemoradiation compared to a negative margin, controlling for extracapsular spread and nodal status (odds ratio, 9.6; 95% confidence interval, 1.6-59.6; P = .02). Preoperative imaging characteristics and subjective radiologic examination of BOT tumors did not correlate with final margin status. Conclusion Positive margins are significantly more likely during TORS BOT resections compared to tonsil resections. More research is needed to help surgeons predict which T1/T2 tumors will be difficult to completely extirpate.

Clinical outcome of dedifferentiated liposarcoma in the extremities: A retrospective case series of 7 patients.

PubMed

Kito, Munehisa; Yoshimura, Yasuo; Isobe, Ken'ichi; Aoki, Kaoru; Suzuki, Shuichiro; Tanaka, Atsushi; Okamoto, Masanori; Sano, Kenji; Kato, Hiroyuki

2016-09-01

Wide resection is the generally recommended surgical treatment for dedifferentiated liposarcoma (DDLPS) in the extremities. However, it may be appropriate to distinguish the surgical margin of low-grade atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLPS) area from the high-grade dedifferentiated area, because the low- and high-grade areas can be clearly separated, both radiologically and histologically. This study re-evaluated the details of surgical margin of DDLPS in the extremities, and aimed to investigate the optimal surgical margin and the usefulness of adjuvant therapy for DDLPS in the extremities. Seven patients diagnosed with DDLPS in the extremities and treated between 1995 and 2013 were analyzed. The use of adjuvant therapy before and after surgery was assessed, and the surgical margins for the ALT/WDLPS and dedifferentiated areas were re-evaluated by using the specimens resected at surgery. Subsequently, the recurrence rates, metastatic rates, and oncological outcomes were examined. Four and three patients had wide (adequate wide margin, n = 3; inadequate wide margin, n = 1) and marginal margins for the dedifferentiated area, respectively, while three and four patients had wide (adequate wide margin, n = 2; inadequate wide margin, n = 1) and marginal margins for the ALT/WDLPS area, respectively. Postoperative radiotherapy was performed in three patients with an inadequate wide margin or a marginal margin for the dedifferentiated area. No patient had local recurrence. Distant metastases occurred in two patients. These patients died of their disease. The other five patients were disease-free. The ALT/WDLPS and dedifferentiated areas in the tumor margin may be better to be considered separately in determining the appropriate resection extent for DDLPS in the extremities. Postoperative radiotherapy may provide good local control for cases with a narrow surgical margin. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy.

PubMed

Osipov, Arsen; Naziri, Jason; Hendifar, Andrew; Dhall, Deepti; Rutgers, Joanne K; Chopra, Shefali; Li, Quanlin; Tighiouart, Mourad; Annamalai, Alagappan; Nissen, Nicholas N; Tuli, Richard

2016-04-01

Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT). We identified 106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were categorized as positive (tumor at ink), ≤1, or >1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), extent of dissection, and positive periportal LNs. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling. In patients receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was associated with improved OS (P=0.049; HR=0.29). In patients receiving adjuvant CT alone, there was a clinically significant benefit to clearing the surgical margin beyond tumor at ink. Having ≥5 NP and positive periportal LN led to significantly worse clinical outcomes. The addition of adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of resection margin distance and LN parameters may identify more patients at risk for locoregional failure who may benefit from adjuvant CRT.

Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy

PubMed Central

Osipov, Arsen; Naziri, Jason; Hendifar, Andrew; Dhall, Deepti; Rutgers, Joanne K.; Chopra, Shefali; Li, Quanlin; Tighiouart, Mourad; Annamalai, Alagappan; Nissen, Nicholas N.

2016-01-01

Background Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT). Methods We identified 106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were categorized as positive (tumor at ink), ≤1, or >1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), extent of dissection, and positive periportal LNs. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling. Results In patients receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was associated with improved OS (P=0.049; HR=0.29). Conclusions In patients receiving adjuvant CT alone, there was a clinically significant benefit to clearing the surgical margin beyond tumor at ink. Having ≥5 NP and positive periportal LN led to significantly worse clinical outcomes. The addition of adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of resection margin distance and LN parameters may identify more patients at risk for locoregional failure who may benefit from adjuvant CRT. PMID:27034792

An evaluation of brachytherapy and external beam radiation used with wide-margin surgical resection in the treatment of extra-abdominal desmoid tumors.

PubMed

Husain, Zain; Benevenia, Joseph; Uglialoro, Anthony D; Beebe, Kathleen S; Patterson, Francis R; Hameed, Meera R; Cathcart, Charles S

2011-05-01

Surgical resection has had control rates of 53% to 77% in the treatment of extra-abdominal desmoid tumors. Surgical excision combined with external beam radiation therapy (EBRT) has had local control rates of up to 83% in some series. The purpose of this study was to evaluate the effectiveness of resection combined with radiotherapy (brachytherapy, EBRT, or both) in the treatment of extra-abdominal desmoid tumors. We retrospectively reviewed the charts of 24 consecutive patients (27 histologically confirmed extra-abdominal desmoid tumors). Patients were included in the study if they had a lesion that was potentially resectable with a wide margin, allowing for limb salvage, and if they did not have a contraindication to radiotherapy. Limb functioning was assessed with the Musculoskeletal Tumor Society (MSTS) scoring system. Seventeen patients (7 men, 10 women) with 19 tumors met the inclusion criteria. Mean age at diagnosis was 23.4 years. Follow-up (mean, 4.28 years) involved serial clinical examinations and magnetic resonance imaging of tumor sites. After surgery, the tumors were treated with brachytherapy (n = 6), EBRT (n = 10), or both (n = 3). Two of the 17 tumors in patients with negative margins of resection recurred locally (local control rate, 88.2%). Mean MSTS score was 29/30 (96.7%). The role of surgery, radiotherapy, chemotherapy, hormone therapy, and other treatments for extra-abdominal desmoid tumors is not well defined. When wide-margin resection and radiotherapy can be performed with limb preservation surgery, local control and complication rates compare favorably with those of other reported methods of treatment. Given the results and limitations of our study, we cannot make a definitive recommendation as to which modality--brachytherapy or EBRT--should be used in the treatment of extra-abdominal desmoid tumors.

Robotic versus laparoscopic surgery for mid or low rectal cancer in male patients after neoadjuvant chemoradiation therapy: comparison of short-term outcomes.

PubMed

Serin, Kursat Rahmi; Gultekin, Fatma Ayca; Batman, Burçin; Ay, Serden; Kapran, Yersu; Saglam, Sezer; Asoglu, Oktar

2015-09-01

The aim of our study was to compare short-term outcomes of robotic and laparoscopic sphincter-saving total mesorectal excision (TME) in male patients with mid-low rectal cancer (RC) after neadjuvant chemoradiotherapy (NCRT). The study was conducted as a retrospective review of a prospectively maintained database, and we analyzed 14 robotic and 65 laparoscopic sphincter saving TME (R-TME and L-TME, respectively) performed by one surgeon between 2005 and 2013. Patient characteristics, perioperative recovery, postoperative complications and and pathology results were compared between the two groups. The patient characteristics did not differ significantly between the two groups. Median operating time was longer in the R-TME than in the L-TME group (182 min versus 140 min). Only two conversions occurred in the L-TME group. No difference was found between groups regarding perioperative recovery and postoperative complication rates. The median number of harvested lymph nodes was higher in the RTME than in the L-TME group (32 versus 23, p = 0.008). The median circumferential margin (CRM) was 10 mm in the R-TME group, 6.5 mm in the L-TME group (p = 0.047. The median distal resection margin (DRM) was 27.5 mm in the R-TME, 15 mm in the L-TME group (p = 0.014). Macroscopic grading of the specimen in the R-TME group was complete in all patients. In the L-TME group, grading was complete in 52 (80%) and incomplete in 13 (20%) cases (p = 0.109). R-TME is a safe and feasible procedure that facilitates performing of TME in male patients with mid-low RC after NCRT.

The Prognostic Value of Varying Definitions of Positive Resection Margin in Patients with Colorectal Cancer Liver Metastases.

PubMed

Wang, Jane; Margonis, Georgios Antonios; Amini, Neda; Andreatos, Nikolaos; Yuan, Chunhui; Damaskos, Christos; Antoniou, Efstathios; Garmpis, Nikolaos; Buettner, Stefan; Barbon, Carlotta; Deshwar, Amar; He, Jin; Burkhart, Richard; Pawlik, Timothy M; Wolfgang, Christopher L; Weiss, Matthew J

2018-04-09

Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width = 0 mm) or a margin width < 1 mm. Consequently, patients with a margin width of 0-1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins. Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin. Five hundred thirty-nine (85.2%) patients had a margin width ≥ 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥ 1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P < 0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04-2.67; P = 0.04, and HR 2.14, 1.46-3.16; P < 0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41-2.65; P < 0.001). Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width > 1 mm. Consequently, a uniform definition of R1 as a margin width < 1 mm should perhaps be employed by future studies.

Fluorescence-guided resection of intracranial VX2 tumor in a preclinical model using 5-aminolevulinic acid (ALA): preliminary results

NASA Astrophysics Data System (ADS)

Bogaards, Arjen; Varma, Abhay; Moriyama, Eduardo H.; Lin, Annie; Giles, Anoja; Bisland, Stuart K.; Lilge, Lothar D.; Bilbao, G. M.; Muller, Paul J.; Wilson, Brian C.

2003-06-01

Fluorescence-guided brain tumor resection may help the neurosurgeon to identify tumor margins that merge imperceptibly into the normal brain tissue and are difficult to identify under white light illumination even using an operating microscope. We compared the amount of residual tumor after white light resection using an operating microscope versus that after fluorescnece-guided resection of an intracranial VX2 tumor in a preclinical model using our previously developed co-axial fluorscence imaging and spectroscopy system, exciting and detecting PpIX fluorescence at 405nm and 635nm respectively. Preliminary results: No fluorescence was present in 3 non-tumor-bearing animals. Fluorescence was present in all 15 tumor-bearing animals after white light resection was completed. To date in 4 rabbits, a decrease in residual tumor was found when using additional fluorescence guided resection compared to white light resection only. Conclusions: ALA induced PpIX fluorescence detects tumor margins not seen under an operation microscope using while light. Using fluorescence imaging to guide tumor resection resulted in a 3-fold decrease in the amount of residual timor. However, these preliminary results indicate that also an additional amount of normal brain is resected, which will be further investigated.

Determination of safe margin in the surgical pathologic specimens of non-small cell carcinoma of the lung.

PubMed

Feizi, Iraj; Sokouti, Mohsen; Golzari, Samad E J; Gojazede, Morteza; Farahnak, Mohammad Reza; Hashemzadeh, Shahriar; Rahimi-Rad, Mohammad Hossein

2013-01-01

Local recurrences of the tumor at the surgical margin are serious problems in pulmonary resections for lung cancer. The aim of this study is to determine the involved margins and safe distances of the resection sites from tumor for prevention of local recurrences. In this prospective study, 66 patients operated for non-small cell lung carcinoma (NSCLC) from Jan 2006 to Sep 2008 were evaluated. After performing pulmonary resections, multiple biopsies were taken up from 5 mm (A), 10 mm (B), 15 mm (C), and 20 mm (D) distance from tumor. The specimens were studied histopathologically. From a total of66 patients with NSCLC admitted to our referral hospital, 25 (38%) had adenocarcinoma, 18 (27.3%) squamous cell carcinoma, 5 (7.5%) large cell carcinoma, 4 (6%) bronchoalveolar cell carcinoma, 4 (6%) adenoid cystic carcinoma, 3 (4.6%) malignant carcinoid tumor and 7 (10.6%) had metastasis. The most common symptoms were dyspnea and cough. Histopathologically tumor positive margins were found in 84.8% (A), 10.6% (B), 4.5% (C), and 0% (D). There was a significant statistically difference between tumor involvement at distances 5 mm (A) versus 10-20 mm (B-D) (P <0.001). A 20 mm distance from the gross tumor is considered as a safe surgical margin in any type of malignant pulmonary resections for prevention of local surgical recurrences if there was no pathologic examination before surgery.

Redefining the Positive Margin in Pancreatic Cancer: Impact on Patterns of Failure, Long-Term Survival and Adjuvant Therapy.

PubMed

Osipov, Arsen; Nissen, Nicholas; Rutgers, Joanne; Dhall, Deepti; Naziri, Jason; Chopra, Shefali; Li, Quanlin; Hendifar, Andrew Eugene; Tuli, Richard

2017-11-01

There is debate regarding the definition and clinical significance of margin clearance in pancreatic ductal adenocarcinoma (PDA). A comprehensive archival analysis of surgical resection margins was performed to determine the effect on locoregional recurrence and survival, and the impact of adjuvant therapy in PDA. We identified 105 patients with resected PDA. Pancreatic, anterior, bile duct, and posterior surgical resection margins (PM; posterior surface, uncinate and vascular groove) were identified. Three pathologists reviewed all archival surgical specimens and recategorized each margin as tumor at ink/transected, <0.5, 0.5-1, >1-2, or >2 mm from the inked surface. The impact of these and other clinical variables was assessed on local control, disease-free survival (DFS), and overall survival (OS). Among all margins, PM clearance up to 2 mm was prognostic of DFS (p = 0.01) and OS (p = 0.01). Dichotomizing the PM at 2 mm revealed it to be an independent predictor of local recurrence-free survival [hazard ratio HR] 0.20, 95% confidence interval [CI] 0.048-0.881, p = 0.033), DFS (HR 0.46, 95% CI 0.22-0.96, p = 0.03), and OS (HR 0.31, 95% CI 0.14-0.74, p = 0.008). A margin status of >2 mm was also prognostic of OS in patients who received adjuvant chemotherapy (HR 0.31, 95% CI 0.11-0.89, p = 0.03), however this difference was mitigated in patients receiving adjuvant chemoradiotherapy (HR 0.40, 95% CI 0.10-1.58, p = 0.19). These data highlight the clinical significance of the PM and the lack of significance of other resection margins. Clearance in excess of 2 mm should be considered to improve long-term clinical outcomes. The use of adjuvant radiotherapy should be strongly considered in patients with PMs <2 mm.

Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance.

PubMed

Neira, Justin A; Ung, Timothy H; Sims, Jennifer S; Malone, Hani R; Chow, Daniel S; Samanamud, Jorge L; Zanazzi, George J; Guo, Xiaotao; Bowden, Stephen G; Zhao, Binsheng; Sheth, Sameer A; McKhann, Guy M; Sisti, Michael B; Canoll, Peter; D'Amico, Randy S; Bruce, Jeffrey N

2017-07-01

OBJECTIVE Extent of resection is an important prognostic factor in patients undergoing surgery for glioblastoma (GBM). Recent evidence suggests that intravenously administered fluorescein sodium associates with tumor tissue, facilitating safe maximal resection of GBM. In this study, the authors evaluate the safety and utility of intraoperative fluorescein guidance for the prediction of histopathological alteration both in the contrast-enhancing (CE) regions, where this relationship has been established, and into the non-CE (NCE), diffusely infiltrated margins. METHODS Thirty-two patients received fluorescein sodium (3 mg/kg) intravenously prior to resection. Fluorescence was intraoperatively visualized using a Zeiss Pentero surgical microscope equipped with a YELLOW 560 filter. Stereotactically localized biopsy specimens were acquired from CE and NCE regions based on preoperative MRI in conjunction with neuronavigation. The fluorescence intensity of these specimens was subjectively classified in real time with subsequent quantitative image analysis, histopathological evaluation of localized biopsy specimens, and radiological volumetric assessment of the extent of resection. RESULTS Bright fluorescence was observed in all GBMs and localized to the CE regions and portions of the NCE margins of the tumors, thus serving as a visual guide during resection. Gross-total resection (GTR) was achieved in 84% of the patients with an average resected volume of 95%, and this rate was higher among patients for whom GTR was the surgical goal (GTR achieved in 93.1% of patients, average resected volume of 99.7%). Intraoperative fluorescein staining correlated with histopathological alteration in both CE and NCE regions, with positive predictive values by subjective fluorescence evaluation greater than 96% in NCE regions. CONCLUSIONS Intraoperative administration of fluorescein provides an easily visualized marker for glioma pathology in both CE and NCE regions of GBM. These findings support the use of fluorescein as a microsurgical adjunct for guiding GBM resection to facilitate safe maximal removal.

Augmented reality in bone tumour resection: An experimental study.

PubMed

Cho, H S; Park, Y K; Gupta, S; Yoon, C; Han, I; Kim, H-S; Choi, H; Hong, J

2017-03-01

We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p < 0.05, one-way analysis of variance). The probabilities of a surgeon obtaining a 10 mm surgical margin with a 3 mm tolerance were 90.2% in AR-assisted resections, and 70.7% in conventional resections. We demonstrated that the accuracy of tumour resection was satisfactory with the help of the AR navigation system, with the tumour shown as a virtual template. In addition, this concept made the navigation system simple and available without additional cost or time. Cite this article: H. S. Cho, Y. K. Park, S. Gupta, C. Yoon, I. Han, H-S. Kim, H. Choi, J. Hong. Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137-143. © 2017 Cho et al.

Augmented reality in bone tumour resection

PubMed Central

Park, Y. K.; Gupta, S.; Yoon, C.; Han, I.; Kim, H-S.; Choi, H.; Hong, J.

2017-01-01

Objectives We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. Methods We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. Results The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p < 0.05, one-way analysis of variance). The probabilities of a surgeon obtaining a 10 mm surgical margin with a 3 mm tolerance were 90.2% in AR-assisted resections, and 70.7% in conventional resections. Conclusion We demonstrated that the accuracy of tumour resection was satisfactory with the help of the AR navigation system, with the tumour shown as a virtual template. In addition, this concept made the navigation system simple and available without additional cost or time. Cite this article: H. S. Cho, Y. K. Park, S. Gupta, C. Yoon, I. Han, H-S. Kim, H. Choi, J. Hong. Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137–143. PMID:28258117

Hospital market concentration, pricing, and profitability in orthopedic surgery and interventional cardiology.

PubMed

Robinson, James C

2011-06-01

To examine the association between hospital market concentration and pricing. Hospitals have been merging into systems that potentially wield bargaining power over private health insurers. Concern is growing among policy makers that these systems may respond to provisions of the 2010 health reform legislation by further increasing consolidation and prices. Multivariate statistical methods were used to evaluate the association between hospital market concentration, prices, and profits (contribution margins) for commercially insured patients admitted for any of 6 major cardiac and orthopedic surgery procedures, adjusting for characteristics of the patient (diagnoses, comorbidities,complications) and of the hospital (size, patient volume, teaching status). Data were obtained on 11,330 patients treated in 61 hospitals in 27 markets across 8 states in 2008. Hospital prices for patients in concentrated markets were higher than hospital prices for otherwise-comparable patients in competitive markets by 25.1% for coronary angioplasty, 13.0%for cardiac rhythm management (CRM) device insertion, 19.2% for total knee replacement, 24.1%for total hip replacement, 19.3% for lumbar spine fusion, and 22.7% for cervical spine fusion (P <.05). Contribution margins were higher in concentrated than in competitive hospital markets by $5259 for angioplasty, $3417 for CRM device insertion, $4123 for total knee replacement, $5889 for total hip replacement, $7931 for lumbar spine fusion, and $4663 for cervical spine fusion (P <.05). Hospitals in concentrated markets charge significantly higher prices and earn significantly higher margins from private insurers than do hospitals in competitive markets.

Evaluation of intraoperative fluorescence imaging-guided surgery in cancer-bearing dogs: a prospective proof-of-concept phase II study in 9 cases.

PubMed

Cabon, Quentin; Sayag, David; Texier, Isabelle; Navarro, Fabrice; Boisgard, Raphaël; Virieux-Watrelot, Dorothée; Ponce, Frédérique; Carozzo, Claude

2016-04-01

The objective was to prospectively evaluate the application of intraoperative fluorescence imaging (IOFI) in the surgical excision of malignant masses in dogs, using a novel lipid nanoparticle contrast agent. Dogs presenting with spontaneous soft-tissue sarcoma or subcutaneous tumors were prospectively enrolled. Clinical staging and whole-body computed tomography (CT) were performed. All the dogs received an intravenous injection of dye-loaded lipid nanoparticles, LipImage 815. Wide or radical resection was realized after CT examination. Real-time IOFI was performed before skin incision and after tumor excision. In cases of radical resection, the lymph nodes (LNs) were imaged. The margin/healthy tissues fluorescence ratio or LN/healthy tissues fluorescence ratio was measured and compared with the histologic margins or LN status. Nine dogs were included. Limb amputation was performed in 3 dogs, and wide resection in 6. No adverse effect was noted. Fluorescence was observed in all 9 of the tumors. The margins were clean in 5 of 6 dogs after wide surgical resection, and the margin/healthy tissues fluorescence ratio was close to 1.0 in all these dogs. Infiltrated margins were observed in 1 case, with a margin/healthy tissues fluorescence ratio of 3.2. Metastasis was confirmed in 2 of 3 LNs, associated with LN/healthy tissues fluorescence ratios of 2.1 and 4.2, whereas nonmetastatic LN was associated with a ratio of 1.0. LipImage 815 used as a contrast agent during IOFI seemed to allow for good discrimination between tumoral and healthy tissues. Future studies are scheduled to evaluate the sensitivity and specificity of IOFI using LipImage 815 as a tracer. Copyright © 2016 Elsevier Inc. All rights reserved.

Risk factors and management of positive horizontal margin in early gastric cancer resected by en bloc endoscopic submucosal dissection.

PubMed

Numata, Norifumi; Oka, Shiro; Tanaka, Shinji; Kagemoto, Kenichi; Sanomura, Yoji; Yoshida, Shigeto; Arihiro, Koji; Shimamoto, Fumio; Chayama, Kazuaki

2015-04-01

Although endoscopic submucosal dissection (ESD) is a widely accepted treatment for early gastric cancer (EGC), there is no consensus regarding the management of positive horizontal margin (HM) despite en bloc ESD. The aim of the current study was to identify the risk factors and optimal management of positive HM in EGCs resected by en bloc ESD. A total of 890 consecutive patients with 1,053 intramucosal EGCs resected by en bloc ESD between April 2005 and June 2011. Clinicopathological data were retrieved retrospectively to assess the positive HM rate, local recurrence rate, risk factors for positive HM, and outcomes of treatment for local recurrent tumor. Positive HM was defined as a margin with direct tumor invasion (type A), the presence of cancerous cells on either end of 2-mm-thick cut sections (type B), or an unclear tumor margin resulting from crush or burn damage (type C). The positive HM rate was 2.0% (21/1,053). The local recurrence rate was 0.3% (3/1,053). All local recurrent tumors were intramucosal carcinomas, and were resected curatively by re-ESD. Multivariate analysis with logistic regression showed tumor location in the upper third of the stomach and lesions not matching the absolute indication to be independent risk factors for positive HM. The risk factors for HM positivity in cases of EGC resected by en bloc ESD are tumor location in the upper third of the stomach and dissatisfaction of the absolute indication for curative ESD.

Study Suggests Smaller Melanoma Excision Margins May Be Option for Some Patients

Cancer.gov

A randomized controlled trial of patients with stage IIA–C cutaneous melanoma thicker than 2-mm found that a 2-cm surgical resection margin is sufficient and is as safe for patients as a 4-cm margin.

Multicenter study of outcome in relation to the type of resection in rectal cancer.

PubMed

Ortiz, Hector; Wibe, Arne; Ciga, Miguel Angel; Kreisler, Esther; Garcia-Granero, Eduardo; Roig, Jose Vicente; Biondo, Sebastiano

2014-07-01

A surgical teaching and auditing program has been implemented to improve the results of treatment for patients with rectal cancer. The aim of this study was to assess the treatment and outcome in patients resected for rectal cancer, focusing on differences relating to the type of resection. This was an observational study. The study took place throughout the network of hospitals that compose the National Health Service in Spain. This study included a consecutive cohort of 3355 patients from the Spanish Rectal Cancer Project. The data of patients who were operated on electively, with curative intent, by anterior resection (n = 2333 [69.5%]), abdominoperineal excision (n = 774 [23.1%]), and Hartmann procedure (n = 248 [7.4%]) between March 2006 and May 2010 were analyzed. Clinical, pathologic, and outcome results were analyzed in relation to the type of surgery performed. After a median follow-up time of 37 months (interquartile range, 30-48 months), bowel perforations were found to be more common in the Hartmann procedure (12.6%) and abdominoperineal groups (10.1%) than in the anterior resection group (2.3%; p < 0.001). Involvement of the circumferential resection margin was also more common in the Hartmann (16.6%) and abdominoperineal groups (14.3%) than in the anterior resection group (6.6%; p < 0.001). Multivariate analysis showed a negative influence on local recurrence, metastasis, survival for advanced stage, intraoperative perforation, invaded circumferential margin, and Hartmann procedure. However, abdominoperineal excision did not significantly influence local recurrence (HR, 0.945; 95% CI, 0.571-1.563; p = 0.825). The main weakness of this study was the voluntary nature of registration in the Spanish Rectal Cancer Project. Although bowel perforation and involvement of the circumferential resection margin were more common after abdominoperineal excision than after anterior resection, this study did not identify abdominoperineal excision as a determinant of local recurrence in the context of 3 years of median follow-up.

Laparoscopic resection of hilar cholangiocarcinoma.

PubMed

Lee, Woohyung; Han, Ho-Seong; Yoon, Yoo-Seok; Cho, Jai Young; Choi, YoungRok; Shin, Hong Kyung; Jang, Jae Yool; Choi, Hanlim

2015-10-01

Laparoscopic resection of hilar cholangiocarcinoma is technically challenging because it involves complicated laparoscopic procedures that include laparoscopic hepatoduodenal lymphadenectomy, hemihepatectomy with caudate lobectomy, and hepaticojejunostomy. There are currently very few reports describing this type of surgery. Between August 2014 and December 2014, 5 patients underwent total laparoscopic or laparoscopic-assisted surgery for hilar cholangiocarcinoma. Two patients with type I or II hilar cholangiocarcinoma underwent radical hilar resection. Three patients with type IIIa or IIIb cholangiocarcinoma underwent extended hemihepatectomy together with caudate lobectomy. The median (range) age, operation time, blood loss, and length of hospital stay were 63 years (43-76 years), 610 minutes (410-665 minutes), 650 mL (450-1,300 mL), and 12 days (9-21 days), respectively. Four patients had a negative margin, but 1 patient was diagnosed with high-grade dysplasia on the proximal resection margin. The median tumor size was 3.0 cm. One patient experienced postoperative biliary leakage, which resolved spontaneously. Laparoscopic resection is a feasible surgical approach in selected patients with hilar cholangiocarcinoma.

Biology of Adenoid Cystic Carcinoma of the Tracheobronchial Tree and Principles of Management.

PubMed

Maziak, Donna E

2018-05-01

Adenoid cystic carcinoma of the trachea is a rare tumor. The mainstay of treatment remains surgical resection, even in the presence of positive margins or metastatic disease. Perineural involvement commonly causes positive margins and should not deter from resection. Knowledge of releasing maneuvers is essential for surgical success. Long-term follow-up is required with patients presenting late and surviving with recurrent disease for years. Copyright © 2018 Elsevier Inc. All rights reserved.

A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins

PubMed Central

Mueller, Jenna L.; Fu, Henry L.; Mito, Jeffrey K.; Whitley, Melodi J.; Chitalia, Rhea; Erkanli, Alaattin; Dodd, Leslie; Cardona, Diana M.; Geradts, Joseph; Willett, Rebecca M.; Kirsch, David G.; Ramanujam, Nimmi

2015-01-01

The goal of resection of soft tissue sarcomas located in the extremity is to preserve limb function while completely excising the tumor with a margin of normal tissue. With surgery alone, one-third of patients with soft tissue sarcoma of the extremity will have local recurrence due to microscopic residual disease in the tumor bed. Currently, a limited number of intraoperative pathology-based techniques are used to assess margin status; however, few have been widely adopted due to sampling error and time constraints. To aid in intraoperative diagnosis, we developed a quantitative optical microscopy toolbox, which includes acriflavine staining, fluorescence microscopy, and analytic techniques called sparse component analysis and circle transform to yield quantitative diagnosis of tumor margins. A series of variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82% and 75%. The utility of this approach was tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78% and 82%. For comparison, if pathology was used to predict local recurrence in this data set, it would achieve a sensitivity of 29% and a specificity of 71%. These results indicate a robust approach for detecting microscopic residual disease, which is an effective predictor of local recurrence. PMID:25994353

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

PubMed

Antic, Tatjana; Taxy, Jerome B

2015-05-01

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

Surgical strategy for bile duct cancer: Advances and current limitations

PubMed Central

Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Hashimoto, Daijo

2011-01-01

The aim of this review is to describe recent advances and topics in the surgical management of bile duct cancer. Radical resection with a microscopically negative margin (R0) is the only way to cure cholangiocarcinoma and is associated with marked survival advantages compared to margin-positive resections. Complete resection of the tumor is the surgeon’s ultimate aim, and several advances in the surgical treatment for bile duct cancer have been made within the last two decades. Multidetector row computed tomography has emerged as an indispensable diagnostic modality for the precise preoperative evaluation of bile duct cancer, in terms of both longitudinal and vertical tumor invasion. Many meticulous operative procedures have been established, especially extended hepatectomy for hilar cholangiocarcinoma, to achieve a negative resection margin, which is the only prognostic factor under the control of the surgeon. A complete caudate lobectomy and resection of the inferior part of Couinaud’s segment IV coupled with right or left hemihepatectomy has become the standard surgical procedure for hilar cholangiocarcinoma, and pylorus-preserving pancreaticoduodenectomy is the first choice for distal bile duct cancer. Limited resection for middle bile duct cancer is indicated for only strictly selected cases. Preoperative treatments including biliary drainage and portal vein embolization are also indicated for only selected patients, especially jaundiced patients anticipating major hepatectomy. Liver transplantation seems ideal for complete resection of bile duct cancer, but the high recurrence rate and decreased patient survival after liver transplant preclude it from being considered standard treatment. Adjuvant chemotherapy and radiotherapy have a potentially crucial role in prolonging survival and controlling local recurrence, but no definite regimen has been established to date. Further evidence is needed to fully define the role of liver transplantation and adjuvant chemo-radiotherapy. PMID:21603318

Accurate, safe, and rapid method of intraoperative tumor identification for totally laparoscopic distal gastrectomy: injection of mixed fluid of sodium hyaluronate and patent blue.

PubMed

Nakagawa, Masatoshi; Ehara, Kazuhisa; Ueno, Masaki; Tanaka, Tsuyoshi; Kaida, Sachiko; Udagawa, Harushi

2014-04-01

In totally laparoscopic distal gastrectomy, determining the resection line with safe proximal margins is often difficult, particularly for tumors located in a relatively upper area. This is because, in contrast to open surgery, identifying lesions by palpating or opening the stomach is essentially impossible. This study introduces a useful method of tumor identification that is accurate, safe, and rapid. On the operation day, after inducing general anesthesia, a mixture of sodium hyaluronate and patent blue is injected into the submucosal layer of the proximal margin. When resecting stomach, all marker spots should be on the resected side. In all cases, the proximal margin is examined histologically by using frozen sections during the operation. From October 2009 to September 2011, a prospective study that evaluated this method was performed. A total of 34 patients who underwent totally laparoscopic distal gastrectomy were enrolled in this study. Approximately 5 min was required to complete the procedure. Proximal margins were negative in all cases, and the mean ± standard deviation length of the proximal margin was 23.5 ± 12.8 mm. No side effects, such as allergy, were encountered. As a method of tumor identification for totally laparoscopic distal gastrectomy, this procedure appears accurate, safe, and rapid.

Positron emission tomography and optical tissue imaging

DOEpatents

Falen, Steven W [Carmichael, CA; Hoefer, Richard A [Newport News, VA; Majewski, Stanislaw [Yorktown, VA; McKisson, John [Hampton, VA; Kross, Brian [Yorktown, VA; Proffitt, James [Newport News, VA; Stolin, Alexander [Newport News, VA; Weisenberger, Andrew G [Yorktown, VA

2012-05-22

A mobile compact imaging system that combines both PET imaging and optical imaging into a single system which can be located in the operating room (OR) and provides faster feedback to determine if a tumor has been fully resected and if there are adequate surgical margins. While final confirmation is obtained from the pathology lab, such a device can reduce the total time necessary for the procedure and the number of iterations required to achieve satisfactory resection of a tumor with good margins.

Refining the 'cucumber' technique for laryngeal biopsy.

PubMed

Robertson, S; Cooper, L; McPhaden, A; MacKenzie, K

2011-06-01

To refine the case selection process for the 'cucumber' mounting system for laryngeal biopsies. We conducted a retrospective audit of cucumber technique specimens taken between January 2002 and December 2008. We analysed the clinical indications for biopsy and the pathological diagnosis, for each specimen, in order to inform our case selection process. The cucumber technique was used for 125 laryngeal specimens. 60 specimens were taken for diagnostic sampling, 46 were taken during endoscopic laser resection, and 19 for overtly benign pathology. The cucumber technique was most useful for the interpretation of margins in endoscopic laser resection specimens. The cucumber technique is most useful for endoscopic resection cases in which tumour, dysplasia or suspicious lesions have been excised. Detailed information on resection margins is invaluable during multidisciplinary team discussions on patient management. Detailed photography of mounted specimens enables both laryngologist and pathologist to orientate and interpret specimens accurately.

Toward real-time tumor margin identification in image-guided robotic brain tumor resection

NASA Astrophysics Data System (ADS)

Hu, Danying; Jiang, Yang; Belykh, Evgenii; Gong, Yuanzheng; Preul, Mark C.; Hannaford, Blake; Seibel, Eric J.

2017-03-01

For patients with malignant brain tumors (glioblastomas), a safe maximal resection of tumor is critical for an increased survival rate. However, complete resection of the cancer is hard to achieve due to the invasive nature of these tumors, where the margins of the tumors become blurred from frank tumor to more normal brain tissue, but in which single cells or clusters of malignant cells may have invaded. Recent developments in fluorescence imaging techniques have shown great potential for improved surgical outcomes by providing surgeons intraoperative contrast-enhanced visual information of tumor in neurosurgery. The current near-infrared (NIR) fluorophores, such as indocyanine green (ICG), cyanine5.5 (Cy5.5), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), are showing clinical potential to be useful in targeting and guiding resections of such tumors. Real-time tumor margin identification in NIR imaging could be helpful to both surgeons and patients by reducing the operation time and space required by other imaging modalities such as intraoperative MRI, and has the potential to integrate with robotically assisted surgery. In this paper, a segmentation method based on the Chan-Vese model was developed for identifying the tumor boundaries in an ex-vivo mouse brain from relatively noisy fluorescence images acquired by a multimodal scanning fiber endoscope (mmSFE). Tumor contours were achieved iteratively by minimizing an energy function formed by a level set function and the segmentation model. Quantitative segmentation metrics based on tumor-to-background (T/B) ratio were evaluated. Results demonstrated feasibility in detecting the brain tumor margins at quasi-real-time and has the potential to yield improved precision brain tumor resection techniques or even robotic interventions in the future.

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

PubMed

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

2013-10-01

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

Prognostic Value of National Comprehensive Cancer Network Lung Cancer Resection Quality Parameters

PubMed Central

Osarogiagbon, Raymond U.; Ray, Meredith A.; Faris, Nicholas R.; Div, M.; Smeltzer, Matthew P.; Stat, M.; Fehnel, Carrie; Houston-Harris, Cheryl; Signore, Raymond S.; McHugh, Laura M.; Levy, Paul; Wiggins, Lynn; Sachdev, Vishal; Robbins, Edward T.

2017-01-01

Background The National Comprehensive Cancer Network (NCCN) surgical resection guidelines for non-small-cell lung cancer (NSCLC) recommend anatomic resection, negative margins, examination of hilar/intrapulmonary lymph nodes, and examination of 3 or more mediastinal nodal stations. We examined the survival impact of these guidelines. Methods Population-based observational study using patient-level data from all curative-intent NSCLC resections from 2004–2013 at 11 institutions in 4 contiguous Dartmouth Hospital Referral Regions in 3 US states. We used an adjusted Cox proportional hazards model to assess the overall survival impact of attaining NCCN guidelines. Results Of 2,429 eligible resections,91% were anatomic, 94% had negative margins, 51% sampled hilar nodes, and 26% examined three or more mediastinal nodal stations. Only 17% of resections met all four criteria, however there was a significant increasing trend from 2% in 2004 to 39% in 2013 (p<0.001). Compared to patients whose surgery missed one or more parameters, the hazard ratio for patients whose surgery met all four criteria was 0.71 (95% confidence interval: 0.59–0.86, p<0.001). Margin status and the nodal staging parameters were most strongly linked with survival. Conclusions Attainment of NCCN surgical quality guidelines was low, but improving, over the past decade in this cohort from a high lung cancer mortality region of the US. The NCCN quality criteria, especially the nodal examination criteria, were strongly associated with survival. The quality of nodal examination should be a focus of quality improvement in NSCLC care. PMID:28366464

Invasive vulvar carcinoma and the question of the surgical margin.

PubMed

Palaia, Innocenza; Bellati, Filippo; Calcagno, Marco; Musella, Angela; Perniola, Giorgia; Panici, Pierluigi B

2011-08-01

To assess the discrepancy between width of surgical margin measured with the naked eye/ruler by a surgeon before removing an invasive vulvar carcinoma, and width of margin measured under microscope by pathologist after fixation of the resected lesion with formalin. Potential relationships between discrepancy and disease recurrence were also investigated. This prospective study was conducted with resected lesions from 86 women who underwent surgery for primary/recurrent invasive vulvar carcinoma. After the surgeon removed the lesions surrounded by 1-2-cm margins, the pathologist determined margin width at the 4 cardinal points of 86 lesions (for a total of 344 margin assessments), first macroscopically and then under the microscope. A safety margin of 0.8 cm on microscopic view was achieved in 83% of cases (112 of 135) when the macroscopic measurement was 1cm, in 91% of cases (58 of 64) when it was 1.5 cm, and 98% of cases (105 of 107) when it was 2 cm. There was a small discrepancy between the surgeon's intent and the microscopic margin measurement, mostly related to tissue shrinkage. A 1-cm surgical margin corresponded to a 0.8-cm margin in microscopic view (the "safe margin") in most cases. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Resection of isolated pelvic recurrences after colorectal surgery: long-term results and predictors of improved clinical outcome.

PubMed

Henry, Leonard R; Sigurdson, Elin; Ross, Eric A; Lee, John S; Watson, James C; Cheng, Jonathan D; Freedman, Gary M; Konski, Andre; Hoffman, John P

2007-07-01

Recurrence in the pelvis after resection of a rectal or rectosigmoid cancer presents a dilemma. Resection offers the only reasonable probability for cure, but at the cost of perioperative morbidity and potential mortality. Clinical decision making remains difficult. Patients resected with curative intent for isolated pelvic recurrences after curative colorectal surgery from 1988 through 2003 were reviewed retrospectively. Clinical and pathologic factors, salvage operations, and complications were recorded. The primary measured outcome was overall survival. Univariate and multivariate analyses were conducted to identify prognostic factors of improved outcome. Ninety patients underwent an attempt at curative resection of a pelvic recurrence with median follow-up of 31 months. Complications occurred in 53% of patients. Operative mortality was 4.4% (4 of 90). Median overall survival was 38 months, and estimated 5-year survival was 40%. A total of 51 of 86 patients had known recurrences (15 local, 16 distant, 20 both). Multivariate analysis revealed that preoperative carcinoembryonic antigen level and final margin status were statistically significant predictors of outcome. The resection of pelvic recurrences after colorectal surgery for cancer can be performed with low mortality and good long-term outcome; however, morbidity from such procedures is high. Low preoperative carcinoembryonic antigen and negative margin of resection predict improved survival.

Resection of isolated pelvic recurrences after colorectal surgery: long-term results and predictors of improved clinical outcome.

PubMed

Henry, Leonard R; Sigurdson, Elin; Ross, Eric A; Lee, John S; Watson, James C; Cheng, Jonathan D; Freedman, Gary M; Konski, Andre; Hoffman, John P

2007-03-01

Recurrence in the pelvis after resection of a rectal or rectosigmoid cancer presents a dilemma. Resection offers the only reasonable probability for cure, but at the cost of marked perioperative morbidity and potential mortality. Clinical decision making remains difficult. Patients who underwent resection with curative intent for isolated pelvic recurrences after curative colorectal surgery from 1988 through 2003 were reviewed retrospectively. Clinical and pathological factors, salvage operations, and complications were recorded. The primary measured outcome was overall survival. Univariate and multivariate analyses were conducted to identify prognostic factors of improved outcome. Ninety patients underwent an attempt at curative resection of a pelvic recurrence; median follow-up was 31 months. Complications occurred in 53% of patients. Operative mortality occurred in 4 (4.4%) of 90 patients. Median overall survival was 38 months, and estimated 5-year survival was 40%. A total of 51 of 86 patients had known recurrences (15 local, 16 distant, 20 both). Multivariate analysis revealed that preoperative carcinoembryonic antigen level and final margin status were statistically significant predictors of outcome. The resection of pelvic recurrences after colorectal surgery for cancer can be performed with low mortality and good long-term outcome; however, morbidity from such procedures is high. Low preoperative carcinoembryonic antigen and negative margin of resection predict improved survival.

Perioperative BRAF inhibitors in locally advanced stage III melanoma.

PubMed

Zippel, Douglas; Markel, Gal; Shapira-Frommer, Roni; Ben-Betzalel, Guy; Goitein, David; Ben-Ami, Eytan; Nissan, Aviram; Schachter, Jacob; Schneebaum, Schlomo

2017-12-01

Stage III malignant melanoma is a heterogeneous disease where those cases deemed marginally resectable or irresecatble are frequently incurable by surgery alone. Targeted therapy takes advantage of the high incidence of BRAF mutations in melanomas, most notably the V600E mutation. These agents have rarely been used in a neoadjuvant setting prior to surgery. Thirteen consecutive patients with confirmed BRAF V600E regionally advanced melanoma deemed marginally resectable or irrresectable, were treated with BRAF inhibiting agents, prior to undergoing surgery. The primary outcome measures were a successful resection and pathological response. Disease-free survival was a secondary outcome measure. Overall, 12/13 patients showed a marked clinical responsiveness to medical treatment, enabling a macroscopically successful resection in all cases. Four patients had a complete pathological response with no viable tumor evident in the resected specimens and eight patients showed evidence of minimally residual tumor with extensive tumoral necrosis and fibrosis. One patient progressed and died before surgery. At a median follow up of 20 months, 10 patients remain free of disease. Perioperative treatment with BRAF inhibiting agents in BRAFV600E mutated Stage III melanoma patients facilitates surgical resection and affords satisfactory disease free survival. © 2017 Wiley Periodicals, Inc.

Borderline resectable pancreatic cancer: conceptual evolution and current approach to image-based classification.

PubMed

Gilbert, J W; Wolpin, B; Clancy, T; Wang, J; Mamon, H; Shinagare, A B; Jagannathan, J; Rosenthal, M

2017-09-01

Diagnostic imaging plays a critical role in the initial diagnosis and therapeutic monitoring of pancreatic adenocarcinoma. Over the past decade, the concept of 'borderline resectable' pancreatic cancer has emerged to describe a distinct subset of patients existing along the spectrum from resectable to locally advanced disease for whom a microscopically margin-positive (R1) resection is considered relatively more likely, primarily due to the relationship of the primary tumor with surrounding vasculature. This review traces the conceptual evolution of borderline resectability from a radiological perspective, including the debates over the key imaging criteria that define the thresholds between resectable, borderline resectable, and locally advanced or metastatic disease. This review also addresses the data supporting neoadjuvant therapy in this population and discusses current imaging practices before and during treatment. A growing body of evidence suggests that the borderline resectable group of patients may particularly benefit from neoadjuvant therapy to increase the likelihood of an ultimately margin-negative (R0) resection. Unfortunately, anatomic and imaging criteria to define borderline resectability are not yet universally agreed upon, with several classification systems proposed in the literature and considerable variance in institution-by-institution practice. As a result of this lack of consensus, as well as overall small patient numbers and lack of established clinical trials dedicated to borderline resectable patients, accurate evidence-based diagnostic categorization and treatment selection for this subset of patients remains a significant challenge. Clinicians and radiologists alike should be cognizant of evolving imaging criteria for borderline resectability given their profound implications for treatment strategy, follow-up recommendations, and prognosis. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Laparoscopic enucleation of liver tumors. Corkscrew technique revisited.

PubMed

Makdissi, Fabio F; Surjan, Rodrigo C T; Machado, Marcel Autran C

2009-03-01

Enucleation of small lesions located near the hepatic surface can be achieved with low morbidity and mortality. This article describes a simple laparoscopic technique for enucleation of liver tumors. After inspection and intraoperative ultrasonography, Glisson's capsule is marked with eletrocautery 2 cm away from the tumor margin. Ultrasonography is used to ascertain surgical margin right before liver transection. Hemihepatic ischemia is applied and marked area is anchored by stitches. The suture is held together by metallic clips and upward traction is performed, facilitating the transection of the parenchyma and correct identification of vascular and biliary structures. This technique has been successfully employed in six consecutive patients. There were four men and two women, mean age 50.3 years. Four patients underwent liver resection for malignant disease and two for benign liver neoplasm. Pathologic surgical margins were free in all cases and mean hospital stay was 2 days. No postoperative mortality was observed. This technique may facilitate laparoscopic nonanatomical liver resection and reduce risk of positive surgical margins. It is also useful in combination with anatomical laparoscopic liver resections such as right or left hemihepatectomies in patients with bilateral liver tumors as occurred in one of our patients.

A paleomagnetic and stable isotope study of the pluton at Rio Hondo near Questa, New Mexico: implications for CRM related to hydrothermal alteration

USGS Publications Warehouse

Hagstrum, J.T.; Johnson, C.M.

1986-01-01

Paleomagnetic and rock magnetic data combined with stable isotope data from the middle Tertiary pluton along the Rio Hondo in northern New Mexico suggest that its magnetic remanence has both thermal (TRM) and high-temperature chemical (CRM) components. Oxygen isotope temperatures indicate that magnetite associated with the more rapidly cooled higher levels of the pluton, and with mafic inclusions and cogenetic rhyolitic dikes sampled at lower levels of exposure, ceased subsolidus recrystallization and isotopic exchange above its Curie temperature (580??C) in the presence of a magmatic fluid. Continued cooling imparted a TRM to these portions of the pluton. The more slowly cooled granodiorite at lower levels has quartz-magnetite isotopic temperatures that are below the Curie temperature of magnetite implying that its magnetization is high-temperature CRM. Sub-Curie isotopic temperatures for other granitic plutons in the western U.S.A. suggest that CRM may be commonly derived from subsolidus interactions between magnetite and magmatic fluids in plutonic rocks. A meteoric-hydrothermal system generated by the cooling Rio Hondo pluton, and not by younger adjacent intrusions, resulted in limited alteration along zones of high permeability near the southern margin of the Rio Hondo pluton, and in more prevasive alteration of the pluton to the north. The meteoric-hydrothermal alteration occurred at relatively high temperatures (> 350??C) and, with the exception of local chloritization, caused little visible alteration of the rocks. The isotopic ratios indicate that little of the magnetite could have grown from or exchanged with a meteoric-hydrothermal fluid. ?? 1986.

Multimodality Management of "Borderline Resectable" Pancreatic Neuroendocrine Tumors: Report of a Single-Institution Experience.

PubMed

Ambe, Chenwi M; Nguyen, Phuong; Centeno, Barbara A; Choi, Junsung; Strosberg, Jonathan; Kvols, Larry; Hodul, Pamela; Hoffe, Sarah; Malafa, Mokenge P

2017-01-01

Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with "borderline resectable disease." For these patients, an optimal treatment approach is lacking. We report our institution's experience with borderline resectable PanNETs using multimodality treatment. We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive. Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression). A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.

Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial.

PubMed

Quirke, Phil; Steele, Robert; Monson, John; Grieve, Robert; Khanna, Subhash; Couture, Jean; O'Callaghan, Chris; Myint, Arthur Sun; Bessell, Eric; Thompson, Lindsay C; Parmar, Mahesh; Stephens, Richard J; Sebag-Montefiore, David

2009-03-07

Local recurrence rates in operable rectal cancer are improved by radiotherapy (with or without chemotherapy) and surgical techniques such as total mesorectal excision. However, the contributions of surgery and radiotherapy to outcomes are unclear. We assessed the effect of the involvement of the circumferential resection margin and the plane of surgery achieved. In this prospective study, the plane of surgery achieved and the involvement of the circumferential resection margin were assessed by local pathologists, using a standard pathological protocol in 1156 patients with operable rectal cancer from the CR07 and NCIC-CTG CO16 trial, which compared short-course (5 days) preoperative radiotherapy and selective postoperative chemoradiotherapy, between March, 1998, and August, 2005. All analyses were by intention to treat. This trial is registered, number ISRCTN 28785842. 128 patients (11%) had involvement of the circumferential resection margin, and the plane of surgery achieved was classified as good (mesorectal) in 604 (52%), intermediate (intramesorectal) in 398 (34%), and poor (muscularis propria plane) in 154 (13%). We found that both a negative circumferential resection margin and a superior plane of surgery achieved were associated with low local recurrence rates. Hazard ratio (HR) was 0.32 (95% CI 0.16-0.63, p=0.0011) with 3-year local recurrence rates of 6% (5-8%) and 17% (10-26%) for patients who were negative and positive for circumferential resection margin, respectively. For plane of surgery achieved, HRs for mesorectal and intramesorectal groups compared with the muscularis propria group were 0.32 (0.16-0.64) and 0.48 (0.25-0.93), respectively. At 3 years, the estimated local recurrence rates were 4% (3-6%) for mesorectal, 7% (5-11%) for intramesorectal, and 13% (8-21%) for muscularis propria groups. The benefit of short-course preoperative radiotherapy did not differ in the three plane of surgery groups (p=0.30 for trend). Patients in the short-course preoperative radiotherapy group who had a resection in the mesorectal plane had a 3-year local recurrence rate of only 1%. In rectal cancer, the plane of surgery achieved is an important prognostic factor for local recurrence. Short-course preoperative radiotherapy reduced the rate of local recurrence for all three plane of surgery groups, almost abolishing local recurrence in short-course preoperative radiotherapy patients who had a resection in the mesorectal plane. The plane of surgery achieved should therefore be assessed and reported routinely.

Role of tumour-free margin distance for loco-regional control in vulvar cancer-a subset analysis of the Arbeitsgemeinschaft Gynäkologische Onkologie CaRE-1 multicenter study.

PubMed

Woelber, Linn; Griebel, Lis-Femke; Eulenburg, Christine; Sehouli, Jalid; Jueckstock, Julia; Hilpert, Felix; de Gregorio, Nikolaus; Hasenburg, Annette; Ignatov, Atanas; Hillemanns, Peter; Fuerst, Sophie; Strauss, Hans-Georg; Baumann, Klaus H; Thiel, Falk C; Mustea, Alexander; Meier, Werner; Harter, Philipp; Wimberger, Pauline; Hanker, Lars Christian; Schmalfeldt, Barbara; Canzler, Ulrich; Fehm, Tanja; Luyten, Alexander; Hellriegel, Martin; Kosse, Jens; Heiss, Christoph; Hantschmann, Peer; Mallmann, Peter; Tanner, Berno; Pfisterer, Jacobus; Richter, Barbara; Neuser, Petra; Mahner, Sven

2016-12-01

A tumour-free pathological resection margin of ≥8 mm is considered state-of-the-art. Available evidence is based on heterogeneous cohorts. This study was designed to clarify the relevance of the resection margin for loco-regional control in vulvar cancer. AGO-CaRE-1 is a large retrospective study. Patients (n = 1618) with vulvar cancer ≥ FIGO stage IB treated at 29 German gynecologic-cancer-centres 1998-2008 were included. This subgroup analysis focuses on solely surgically treated node-negative patients with complete tumour resection (n = 289). Of the 289 analysed patients, 141 (48.8%) had pT1b, 140 (48.4%) pT2 and 8 (2.8%) pT3 tumours. One hundred twenty-five (43.3%) underwent complete vulvectomy, 127 (43.9%) partial vulvectomy and 37 (12.8%) radical local excision. The median minimal resection margin was 5 mm (1 mm-33 mm); all patients received groin staging, in 86.5% with full dissection. Median follow-up was 35.1 months. 46 (15.9%) patients developed recurrence, thereof 34 (11.8%) at the vulva, after a median of 18.3 months. Vulvar recurrence rates were 12.6% in patients with a margin <8 mm and 10.2% in patients with a margin ≥8 mm. When analysed as a continuous variable, the margin distance had no statistically significant impact on local recurrence (HR per mm increase: 0.930, 95% CI: 0.849-1.020; p = 0.125). Multivariate analyses did also not reveal a significant association between the margin and local recurrence neither when analysed as continuous variable nor categorically based on the 8 mm cutoff. Results were consistent when looking at disease-free-survival and time-to-recurrence at any site (HR per mm increase: 0.949, 95% CI: 0.864-1.041; p = 0.267). The need for a minimal margin of 8 mm could not be confirmed in the large and homogeneous node-negative cohort of the AGO-CaRE database. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins

PubMed Central

Keating, Jane J.; Okusanya, Olugbenga T.; De Jesus, Elizabeth; Judy, Ryan; Jiang, Jack; Deshpande, Charuhas; Nie, Shuming; Low, Philip; Singhal, Sunil

2017-01-01

Purpose During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection. Procedures Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in 3 humans with lung adenocarcinoma. Results The peak tumor-to background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 hours and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30% of mice with positive margins. Molecular imaging identified an additional 50% of residual tumor deposits (P<0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5. Conclusions Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection. PMID:26228697

Prognosis of Primary and Recurrent Chondrosarcoma of the Rib.

PubMed

Roos, Eva; van Coevorden, Frits; Verhoef, Cornelis; Wouters, Michel W; Kroon, Herman M; Hogendoorn, Pancras C W; van Houdt, Winan J

2016-03-01

Chondrosarcoma of the rib is a rare disease. Although surgery is the only curative treatment option, rib resection with an adequate margin can be challenging and local recurrence is a frequent problem. In this study, the prognosis of primary and recurrent chondrosarcoma of the rib is reported. Retrospective analysis was performed of patients treated for chondrosarcoma of the rib between 1984 and 2014 in three major tertiary referral centers in The Netherlands. Clinical and histopathological features were analyzed for their prognostic value using Kaplan-Meier and Cox proportional hazard analysis. Endpoints were set at local recurrent disease, metastasis rate, or death. Overall, 76 patients underwent a resection for a primary chondrosarcoma, and 26 patients underwent a resection for a recurrent chondrosarcoma. Five-year overall survival in the primary group was 90%, local recurrence rate was 17%, and metastasis rate was 12%. The 5-year outcome after recurrent chondrosarcoma was lower, with an overall survival of 65%, local recurrence rate of 27%, and metastasis rate of 27%. For primary chondrosarcoma, tumor size >5 cm and a positive resection margin were correlated with worse overall survival [hazard ratio (HR) 3.28, 95% confidence interval (CI) 1.03-10.44; HR 2.92, 95% CI 1.03-8.25). A higher histological grade was correlated with a higher local recurrence and metastasis rate (HR 5.92, 95% CI 1.11-31.65; HR 6.96, 95% CI 1.15-42.60). Surgical resection of both primary and recurrent chondrosarcoma of the rib is an effective treatment strategy. The oncological outcome after surgery is worse in tumors >5 cm, in tumors with positive resection margins and grade 3 chondrosarcoma.

[Experimental rationale for a procedure for correction of the residual cavity in hydatidectomy].

PubMed

Biriukov, Iu V; Streliaeva, A V; Sadykov, R V; Lazareva, N B; Sadykov, V M; Chebyshev, N V

2010-01-01

Thirty-six piglets (15 days old) were inoculated with Echinococcus according to the authors' procedure. Hepatic hydatid cyst growth in the piglets was ultrasonographically monitored 3 months after inoculation. In 15 piglets, the size of hepatic hydatid cysts was as high as 6.5 x 8.5 cm 5 months after infection. The cavity of larvocystic fibrous capsule was eliminated, by inverting the resection margins inward with interrupted catgut sutures. For content aspiration, the cystic bed was occasionally drained by a polyvinyl chloride tube with two side holes, which was brought outward through an individual incision. Thesubhepatic area was also drained by a "cigar" tampon through an individual incision. The wound healed in layers, tightly. Marginal resection of the liver was performed to stimulate regenerative processes in the resected area.

A novel approach emphasising intra-operative superficial margin enhancement of head-neck tumours with narrow-band imaging in transoral robotic surgery.

PubMed

Vicini, C; Montevecchi, F; D'Agostino, G; DE Vito, A; Meccariello, G

2015-06-01

The primary goal of surgical oncology is to obtain a tumour resection with disease-free margins. Transoral robotic surgery (TORS) for surgical treatment of head-neck cancer is commensurate with standard treatments. However, the likelihood of positive margins after TORS is up to 20.2% in a recent US survey. The aim of this study is to evaluate the efficacy and the feasibility of narrow-band imaging (NBI) during TORS in order to improve the ability to achieve disease-free margins during tumour excision. The present study was conducted at the ENT, Head- Neck Surgery and Oral Surgery Unit, Department of Special Surgery, Morgagni Pierantoni Hospital, Azienda USL Romagna. From March 2008 to January 2015, 333 TORS were carried out for malignant and benign diseases. For the present study, we retrospectively evaluated 58 biopsy-proven squamous cell carcinoma patients who underwent TORS procedures. Patients were divided into 2 groups: (1) 32 who underwent TORS and intra-operative NBI evaluation (NBI-TORS); (2) 21 who underwent TORS with standard intra-operative white-light imaging (WLITORS). Frozen section analysis of margins on surgical specimens showed a higher rate of negative superficial lateral margins in the NBI-TORS group compared with the WLI-TORS group (87.9% vs. 57.9%, respectively, p = 0.02). The sensitivity and specificity of intra-operative use of NBI, respectively, were 72.5% and 66.7% with a negative predictive value of 87.9%. Tumour margin enhancement provided by NBI associated with magnification and 3-dimensional view of the surgical field might increase the capability to achieve an oncologically-safe resection in challenging anatomical areas where minimal curative resection is strongly recommended for function preservation.

The Status of Contemporary Image-Guided Modalities in Oncologic Surgery

PubMed Central

Rosenthal, Eben L; Warram, Jason M; Bland, Kirby I; Zinn, Kurt R

2014-01-01

Surgical resection remains the cornerstone of therapy for patients with early stage solid malignancies and more than half of all cancer patients undergo surgery each year. The technical ability of the surgeon to obtain clear surgical margins at the initial resection remains crucial to improve overall survival and long-term morbidity. Current resection techniques are largely based on subjective and subtle changes associated with tissue distortion by invasive cancer. As a result, positive surgical margins occur in a significant portion of tumor resections, which is directly correlated with a poor outcome. A variety of cancer imaging techniques have been adapted or developed for intraoperative surgical guidance that have been shown to improve functional and oncologic outcomes in randomized clinical trials. There are also a large number of novel, cancer-specific contrast agents that are in early stage clinical trials and preclinical development that demonstrate significant promise to improve real-time detection of subclinical cancer in the operative setting. PMID:25599326

Correlation between Resection Margin and Disease Recurrence with a Restricted Cubic Spline Model in Patients with Resected Hepatocellular Carcinoma.

PubMed

Lee, Woohyung; Han, Ho-Seong; Ahn, Soyeon; Yoon, Yoo-Seok; Cho, Jai Young; Choi, YoungRok

2018-01-17

The relationship between resection margin (RM) and recurrence of resected hepatocellular carcinoma (HCC) is unclear. We reviewed clinical data for 419 patients with HCC. The oncologic outcomes were compared between 2 groups of patients classified according to the inflexion point of the restricted cubic spline plot. The patients were divided according to an RM of <1 cm (n = 233; narrow RM group) or ≥1 cm (n = 186; wide RM group). The 5-year recurrence-free survival (RFS) rate was lower (34.8 vs. 43.8%, p = 0.042) and recurrence near the resection site was more frequent (4.7 vs. 0%, p = 0.010) in the narrow RM group. Patients with multiple lesions, or prior transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) were excluded from subgroup analyses. In patients with a 2-5 cm HCC, the 5-year RFS was greater in the wide RM group (54.4 vs. 32.5%, p = 0.036). Narrow RM (hazard ratio 1.750, 95% CI 1.029-2.976, p = 0.039) was independently associated with disease recurrence. In patients with a single 2-5 cm HCC without prior TACE/RFA, an RM of ≥1 cm was associated with lower risk of recurrence after liver resection. © 2018 S. Karger AG, Basel.

What is the significance of a microscopically positive resection margin in the curative-intent treatment of rectal adenocarcinoma? A retrospective study.

PubMed

Fekete, Z; Muntean, A; Irimie, A; Hica, S; Resiga, L; Todor, N; Nagy, V

2013-01-01

The aim of this study was to analyze the characteristics of patients with rectal cancer operated with a microscopic positive margin (R1) and thus avoid these situations or adapt treatment in these particular cases. We reviewed all the pathology data of resected specimens from patients with rectal or recto-sigmoid cancer operated with curative intent at the Institute of Oncology "Prof. Dr. Ion Chiricuta" between 2000-2011 (763 patients in 12 years) and the pathology files of patients from other institutions referred for adjuvant treatment to our hospital (318 patients). We included patients with anterior resection, Hartmann's procedure and abdomino-perineal resection, but we excluded patients with local excision and patients with R2/R1 at first, but R0 after re-resection (56 patients). We have identified 31 patients with R1, but had to exclude one case from analysis because this patient was lost to follow-up. With surgery alone the local relapse (LR) was unavoidable. In the neoadjuvant chemoradiation (CRT) group 85.7% of the patients did not develop LR despite of R1. In the adjuvant CRT cohort 50% of the patients were LR-free at 2 years after conventional radiotherapy (p<0.01). Based on these results it is concluded that a clear resection margin is extremely important for the local control of rectal cancer, because it cannot be always compensated by adjuvant CRT. In R1 cases neoadjuvant CRT seems to offer better prognosis than adjuvant CRT. To avoid R1 and its consequences a good quality control of total mesorectal excision (TME) is needed and CRT should be done before and not after surgery. R1 after primary surgery needs to be compensated by re-resection if possible, otherwise probably high dose radiotherapy with chemotherapy is needed.

Assessment of margins in resection specimens for head and neck malignancies.

PubMed

Janjua, Omer Sefvan; Ahmed, Waseem; Qureshi, Sana Mehmood; Khan, Tariq Sarfaraz; Ahmed, Ashfaq; Alamgir, Wajiha

2013-04-01

To determine the relative frequency of clear, close and involved margins in resection specimens for head and neck malignancies. An observational study. The Department of Oral and Maxillofacial Surgery, Armed Forces Institute of Dentistry, Rawalpindi and the Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from January 2008 to December 2010. Tumour registers and computer data bases in the department of Histopathology of Armed Forces Institute of Pathology, Rawalpindi, were analyzed for the cases of malignancies involving head and neck region that were sent for histopathological analysis after resection in the last three years. Histopathology reports were obtained. The data regarding age, gender, site, type of malignancy and margin status (clear, close or involved) was recorded on specially designed proformas for the study and later on analyzed by using SPSS version 17.0. Results were expressed. A total of 319 cases were registered in the study duration. The age of the patients ranged from 22-90 years (mean 59.5 + 14.1 years). Male to female ratio was 1.53:1. One hundred and thirty six (42.6%) were squamous cell carcinoma (SCC), 163 were basal cell carcinomas (BCC, 51.0%); the rest included 18 salivary gland malignancies (5.7%) and one carcino-sarcoma (0.31%) and chondrosarcoma each. All margins were found clear in 137 patients (42.9%); involved in 168 cases (52.7%) and close in 14 cases (4.4%). Margin clearance could not be achieved in more than 50% cases, this can lead to poor prognosis. Hence, methods should be adopted to improve the margin clearance in various head and neck malignancies.

Management and prognosis of locally recurrent rectal cancer - A national population-based study.

PubMed

Westberg, Karin; Palmer, Gabriella; Hjern, Fredrik; Johansson, Hemming; Holm, Torbjörn; Martling, Anna

2018-01-01

The rate of local recurrence of rectal cancer (LRRC) has decreased but the condition remains a therapeutic challenge. This study aimed to examine treatment and prognosis in patients with LRRC in Sweden. Special focus was directed towards potential differences between geographical regions and time periods. All patients with LRRC as first event, following primary surgery for rectal cancer performed during the period 1995-2002, were included in this national population-based cohort-study. Data were collected from the Swedish Colorectal Cancer Registry and from medical records. The cohort was divided into three time periods, based on the date of diagnosis of the LRRC. In total, 426 patients fulfilled the inclusion criteria. Treatment with curative intent was performed in 149 patients (35%), including 121 patients who had a surgical resection of the LRRC. R0-resection was achieved in 64 patients (53%). Patients with a non-centrally located tumour were more likely to have positive resection margins (R1/R2) (OR 5.02, 95% CI:2.25-11.21). Five-year survival for patients resected with curative intent was 43% after R0-resection and 14% after R1-resection. There were no significant differences in treatment intention or R0-resection rate between time periods or regions. The risk of any failure was significantly higher in R1-resected patients compared with R0-resected patients (HR 2.04, 95% CI:1.22-3.40). A complete resection of the LRRC is essential for potentially curative treatment. Time period and region had no influence on either margin status or prognosis. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

What is the best surgical margin for a Basal cell carcinoma: a meta-analysis of the literature.

PubMed

Gulleth, Yusuf; Goldberg, Nelson; Silverman, Ronald P; Gastman, Brian R

2010-10-01

Current management of basal cell carcinoma is surgical excision. Most resections use predetermined surgical margins. The basis of ideal resection margins is almost completely from retrospective data and mainly from small case series. This article presents a systematic analysis from a large pool of data to provide a better basis of determining ideal surgical margin. A systematic analysis was performed on data from 89 articles from a larger group of 973 articles selected from the PubMed database. Relevant inclusion and exclusion criteria were applied to all articles reviewed and the data were entered into a database for statistical analysis. The total number of lesions analyzed was 16,066; size ranged from 3 to 30 mm (mean, 11.7 ± 5.9 mm). Surgical margins ranged from 1 to 10 mm (mean, 3.9 ± 1.4 mm). Negative surgical margins ranged 45 to 100 percent (mean, 86 ± 12 percent). Recurrence rates for 5-, 4-, 3-, and 2-mm surgical margins were 0.39, 1.62, 2.56, and 3.96 percent, respectively. Pooled data for incompletely excised margins have an average recurrence rate of 27 percent. A 3-mm surgical margin can be safely used for nonmorpheaform basal cell carcinoma to attain 95 percent cure rates for lesions 2 cm or smaller. A positive pathologic margin has an average recurrence rate of 27 percent.

The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

PubMed

Fridman, Eran; Na'ara, Shorook; Agarwal, Jaiprakash; Amit, Moran; Bachar, Gideon; Villaret, Andrea Bolzoni; Brandao, Jose; Cernea, Claudio R; Chaturvedi, Pankaj; Clark, Jonathan; Ebrahimi, Ardalan; Fliss, Dan M; Jonnalagadda, Sashikanth; Kohler, Hugo F; Kowalski, Luiz P; Kreppel, Matthias; Liao, Chun-Ta; Patel, Snehal G; Patel, Raj P; Robbins, K Thomas; Shah, Jatin P; Shpitzer, Thomas; Yen, Tzu-Chen; Zöller, Joachim E; Gil, Ziv

2018-05-14

Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Cervical Rotatory Manipulation Decreases Uniaxial Tensile Properties of Rabbit Atherosclerotic Internal Carotid Artery

PubMed Central

Qi, Ji; Zhang, Lei; Chen, Chao; Mondal, Shubhro; Ping, Kaike; Chen, Yili

2017-01-01

Objective. To investigate the effects of one of the Chinese massage therapies, cervical rotatory manipulation (CRM), on uniaxial tensile properties of rabbit atherosclerotic internal carotid artery (ICA). Methods. 40 male purebred New Zealand white rabbits were randomly divided into CRM-Model group, Non-CRM-Model group, CRM-Normal group, and Non-CRM-Normal group. After modeling (atherosclerotic model) and intervention (CRM or Non-CRM), uniaxial tensile tests were performed on the ICAs to assess the differences in tensile mechanical properties between the four groups. Results. Both CRM and modeling were the main effects affecting physiological elastic modulus (PEM) of ICA. PEM in CRM-Model group was 1.81 times as much as Non-CRM-Model group, while the value in CRM-Model group was 1.34 times as much as CRM-Normal group. Maximum elastic modulus in CRM-Model group was 1.80 times as much as CRM-Normal group. Max strains in CRM-Model group and Non-CRM-Model group were 30.98% and 28.71% lower than CRM-Normal group and Non-CRM-Normal group, respectively. However, whether treated with CRM or not, the uniaxial tensile properties of healthy ICAs were not statistically different. Conclusion. CRM may decrease the uniaxial tensile properties of rabbit arteriosclerotic ICA, but with no effect on normal group. The study will aid in the meaningful explanation of the controversy about the harmfulness of CRM and the suitable population of CRM. PMID:28303160

Osteosarcoma of the spine: prognostic variables for local recurrence and overall survival, a multicenter ambispective study.

PubMed

Dekutoski, Mark B; Clarke, Michelle J; Rose, Peter; Luzzati, Alessandro; Rhines, Laurence D; Varga, Peter P; Fisher, Charles G; Chou, Dean; Fehlings, Michael G; Reynolds, Jeremy J; Williams, Richard; Quraishi, Nasir A; Germscheid, Niccole M; Sciubba, Daniel M; Gokaslan, Ziya L; Boriani, Stefano

2016-07-01

OBJECTIVE Primary spinal osteosarcomas are rare and aggressive neoplasms. Poor outcomes can occur, as obtaining marginal margins is technically demanding; further Enneking-appropriate en bloc resection can have significant morbidity. The goal of this study is to identify prognostic variables for local recurrence and mortality in surgically treated patients diagnosed with a primary osteosarcoma of the spine. METHODS A multicenter ambispective database of surgically treated patients with primary spine osteosarcomas was developed by AOSpine Knowledge Forum Tumor. Patient demographic, diagnosis, treatment, perioperative morbidity, local recurrence, and cross-sectional survival data were collected. Tumors were classified in 2 cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI), as defined by pathology margin matching Enneking-recommended surgical margins. Prognostic variables were analyzed in reference to local recurrence and survival. RESULTS Between 1987 and 2012, 58 patients (32 female patients) underwent surgical treatment for primary spinal osteosarcoma. Patients were followed for a mean period of 3.5 ± 3.5 years (range 0.5 days to 14.3 years). The median survival for the entire cohort was 6.7 years postoperative. Twenty-four (41%) patients died, and 17 (30%) patients suffered a local recurrence, 10 (59%) of whom died. Twenty-nine (53%) patients underwent EA resection while 26 (47%) patients underwent EI resection with a postoperative median survival of 6.8 and 3.7 years, respectively (p = 0.048). EI patients had a higher rate of local recurrence than EA patients (p = 0.001). Patient age, previous surgery, biopsy type, tumor size, spine level, and chemotherapy timing did not significantly influence recurrence and survival. CONCLUSIONS Osteosarcoma of the spine presents a significant challenge, and most patients die in spite of aggressive surgery. There is a significant decrease in recurrence and an increase in survival with en bloc resection (EA) when compared with intralesional resection (EI). The effect of adjuvant and neoadjuvant chemotherapeutics, as well as method of biopsy, requires further exploration.

A multicenter cohort study of spinal osteoid osteomas: results of surgical treatment and analysis of local recurrence.

PubMed

Quraishi, Nasir A; Boriani, Stefano; Sabou, Silviu; Varga, Peter P; Luzzati, Alessandro; Gokaslan, Ziya L; Fehlings, Michael G; Fisher, Charles G; Dekutoski, Mark B; Rhines, Laurence D; Reynolds, Jeremy J; Germscheid, Niccole M; Bettegowda, Chetan; Williams, Richard P

2017-03-01

Spinal osteoid osteomas are benign primary tumors arising predominantly from the posterior column of the spine. These "osteoblastic" lesions have traditionally been treated with intralesional excision. The purpose of the present study was to review the treatment and local recurrence rates for symptomatic spinal osteoid osteomas. Multicenter ambispective cross-sectional observational cohort study. During the study period, a total of 84 patients (65 males, 19 females) were diagnosed with a spinal osteoid osteoma and received surgical treatment. The mean age at surgery was 21.8 ± 9.0 years (range: 6.7-52.4 years) and the mean follow-up was 2.7 years (13 days-14.5 years). Local recurrence, perioperative morbidity, and cross-sectional survival. Using the AOSpine Knowledge Forum Tumor multicenter ambispective database, surgically treated osteoid osteoma cases were identified. Patient demographic, clinical and diagnostic, treatment, local recurrence, perioperative morbidity, and cross-sectional survival data were collected and retrieved. Descriptive statistics were summarized using mean/standard deviation or frequency/percentage. In our study, most of the tumors were localized in the mobile spine (81 of 84 [96%]); all patients reported pain as a symptom. According to the postoperative assessment, 10 (12%) patients received an en bloc resection with marginal or wide margins, whereas two (2%) patients received en bloc resections with intralesional margins, 69 (82%) patients were treated by piecemeal "intralesional" resection, and three (4%) patients were not assessed. A total of six patients (7%) experienced a local recurrence, all of which occurred in patients who had received an intralesional resection. Benign bone-forming tumors of the spine are uncommon. Most patients in our series underwent a piecemeal resection with intralesional margins. This remains safe with a low local recurrence rate. En bloc excision may provide more chance of complete excision of the nidus but is not mandatory. The importance of complete excision of the nidus cannot be overemphasized. Copyright © 2016 Elsevier Inc. All rights reserved.

Adenoid cystic carcinoma of the skull base: results with an aggressive multidisciplinary approach.

PubMed

Ramakrishna, Rohan; Raza, Shaan M; Kupferman, Michael; Hanna, Ehab; DeMonte, Franco

2016-01-01

OBJECT Adenoid cystic carcinoma (ACC) is a locally aggressive tumor of salivary gland origin. Little data exist to guide treatment when this tumor extends to involve the structures of the skull base. METHODS Fifty-one patients with a diagnosis of ACC affecting the skull base were identified from a prospective database at MD Anderson Cancer Center (from 1992 to 2010). RESULTS Median follow-up for study patients was 6.75 years. The 5- and 10-year overall survival (OS) rates were 78% and 50%, respectively. Sixty-six percent of patients had progression of their disease. The 5- and 10-year progression-free survival (PFS) rates were 46.7% and 21.0%, respectively. Gross-total resection was achieved in 75% of patients, with 49% having microscopically negative margins at the time of first operation. On univariate analysis, resections with microscopically negative margins were associated with a significant OS advantage (20.1 ± 3.3 years) compared with resections that left residual disease, even if microscopic (10.3 ± 1.6 years, p = 0.035). In patients who underwent reoperation, the effect persisted, with improved OS in those with negative margins (21.4 ± 0.0 vs 16.7 ± 4.0 years, p = 0.06). The use of adjuvant radiotherapy was associated with an OS advantage (16.2 ± 2.5 vs 5.5 ± 2.2 years, p = 0.03) at initial diagnosis and improved PFS (7.8 ± 1.0 vs 2.1 ± 0.62 years, p = 0.005), whereas repeat irradiation provided no benefit. The use of adjuvant chemotherapy at diagnosis or at recurrence was not associated with any significant advantage. Multivariate analysis revealed margin-negative resection at initial operation and at recurrence retained OS significance, even after controlling for age, radiation therapy, and T stage. CONCLUSIONS ACC of the skull base is best treated with a multidisciplinary approach aimed at maximal, safe resection. Adjuvant radiotherapy should be offered, whereas chemotherapy does not confer benefit.

Resection margin influences survival after pancreatoduodenectomy for distal cholangiocarcinoma.

PubMed

Chua, Terence C; Mittal, Anubhav; Arena, Jenny; Sheen, Amy; Gill, Anthony J; Samra, Jaswinder S

2017-06-01

Distal cholangiocarcinoma remains a rare cancer associated with a dismal outcome. There is a lack of effective treatment options and where disease is amendable to resection, surgery affords the best potential for long-term survival. The aim of this study was to examine the survival outcomes and prognostic factors of patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma. Between January 2004 to May 2016, patients who had undergone pancreatoduodenectomy with histologically proven distal cholangiocarcinoma were identified. Clinicopathologic data and survival outcomes were reported. Pancreatoduodenectomy alone was performed in 20 patients (71%) and eight patients (29%) required concomitant vascular resection. The major complication rate was 43% (n = 12). Nineteen patients (68%) had node positive disease. Eighteen patients (64%) had R0 resection. The median survival was 36 months (95%CI 9.7 to 63.8) and 5-year survival rate was 24%. Univariate analysis identified ASA (P < 0.001), tumor grade (P = 0.009) and margin status (P = 0.042) as prognostic factors associated with survival. Long-term survival may be achieved in selected patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma, especially in patients who achieved an R0 resection. Copyright © 2016 Elsevier Inc. All rights reserved.

Safety of laparoscopic colorectal surgery in a low-volume setting: review of early and late outcome.

PubMed

Gandy, Robert C; Berney, Christophe R

2014-01-01

Background. There is increasing evidence suggesting that the laparoscopic technique is the treatment of choice for large bowel resection, including for malignancy. The purpose of the study was to assess whether general surgeons, with particular skills in advanced laparoscopy, can adequately provide safe laparoscopic colorectal resections in a low-volume setting. Methods. A retrospective review of prospectively collected case series of all laparoscopic colorectal resections performed under the care of a single general surgeon is presented. The primary endpoint was postoperative clinical outcome in terms of morbidity and mortality. Secondary endpoints were adequacy of surgical margins and number of lymph nodes harvested for colorectal cancer cases. Results. Seventy-three patients underwent 75 laparoscopic resections between March, 2003, and May, 2011. There was no elective mortality and the overall 30-day postoperative morbidity was 9.3%. Conversion and anastomotic leakage rates were both 1.3%, respectively. None of the malignant cases had positive margins and the median number of lymph nodes retrieved was 17. Conclusions. Our results support the view that general surgeons with advanced skills in minimally invasive surgery may safely perform laparoscopic colorectal resection in a low-volume setting in carefully selected patient cases.

Safety of Laparoscopic Colorectal Surgery in a Low-Volume Setting: Review of Early and Late Outcome

PubMed Central

Gandy, Robert C.; Berney, Christophe R.

2014-01-01

Background. There is increasing evidence suggesting that the laparoscopic technique is the treatment of choice for large bowel resection, including for malignancy. The purpose of the study was to assess whether general surgeons, with particular skills in advanced laparoscopy, can adequately provide safe laparoscopic colorectal resections in a low-volume setting. Methods. A retrospective review of prospectively collected case series of all laparoscopic colorectal resections performed under the care of a single general surgeon is presented. The primary endpoint was postoperative clinical outcome in terms of morbidity and mortality. Secondary endpoints were adequacy of surgical margins and number of lymph nodes harvested for colorectal cancer cases. Results. Seventy-three patients underwent 75 laparoscopic resections between March, 2003, and May, 2011. There was no elective mortality and the overall 30-day postoperative morbidity was 9.3%. Conversion and anastomotic leakage rates were both 1.3%, respectively. None of the malignant cases had positive margins and the median number of lymph nodes retrieved was 17. Conclusions. Our results support the view that general surgeons with advanced skills in minimally invasive surgery may safely perform laparoscopic colorectal resection in a low-volume setting in carefully selected patient cases. PMID:24799890

Independent Predictors of Prognosis Based on Oral Cavity Squamous Cell Carcinoma Surgical Margins.

PubMed

Buchakjian, Marisa R; Ginader, Timothy; Tasche, Kendall K; Pagedar, Nitin A; Smith, Brian J; Sperry, Steven M

2018-05-01

Objective To conduct a multivariate analysis of a large cohort of oral cavity squamous cell carcinoma (OCSCC) cases for independent predictors of local recurrence (LR) and overall survival (OS), with emphasis on the relationship between (1) prognosis and (2) main specimen permanent margins and intraoperative tumor bed frozen margins. Study Design Retrospective cohort study. Setting Tertiary academic head and neck cancer program. Subjects and Methods This study included 426 patients treated with OCSCC resection between 2005 and 2014 at University of Iowa Hospitals and Clinics. Patients underwent excision of OCSCC with intraoperative tumor bed frozen margin sampling and main specimen permanent margin assessment. Multivariate analysis of the data set to predict LR and OS was performed. Results Independent predictors of LR included nodal involvement, histologic grade, and main specimen permanent margin status. Specifically, the presence of a positive margin (odds ratio, 6.21; 95% CI, 3.3-11.9) or <1-mm/carcinoma in situ margin (odds ratio, 2.41; 95% CI, 1.19-4.87) on the main specimen was an independent predictor of LR, whereas intraoperative tumor bed margins were not predictive of LR on multivariate analysis. Similarly, independent predictors of OS on multivariate analysis included nodal involvement, extracapsular extension, and a positive main specimen margin. Tumor bed margins did not independently predict OS. Conclusion The main specimen margin is a strong independent predictor of LR and OS on multivariate analysis. Intraoperative tumor bed frozen margins do not independently predict prognosis. We conclude that emphasis should be placed on evaluating the main specimen margins when estimating prognosis after OCSCC resection.

Role of specimen US for predicting resection margin status in breast conserving therapy.

PubMed

Moschetta, M; Telegrafo, M; Introna, T; Coi, L; Rella, L; Ranieri, V; Cirili, A; Stabile Ianora, A A; Angelelli, G

2015-01-01

To assess the diagnostic accuracy of specimen ultrasound (US) for predicting resection margin status in women undergoing breast conserving therapy for US-detected cancer, having the histological findings as the reference standard. A total of 132 consecutive patients (age range, 34-87 years; mean, 51 years) underwent breast-conserving surgery for US-detected invasive breast cancer. All surgical specimens underwent US examination. The presence of lesion within the specimen and its distance from the specimen margins were assessed considering a threshold distance between the lesion and specimen margins of 10 mm. US findings were then compared with the pathological ones and specimen US. Sensitivity, specificity, diagnostic accuracy, positive (PPV) and negative predictive values (NPV) for predicting histological margin status were evaluated, having the histological findings as the reference standard. The histological examination detected invasive ductal carcinoma in 96/132 (73%) cases, invasive lobular carcinoma in 32/132 (24%), mucinous carcinoma in 4/132 (3%). The pathological margin analysis revealed 96/132 (73%) negative margins and 36 (27%) close/positive margins. US examination detected all 132 breast lesions within the surgical specimens. 110 (83%) negative margins and 22 (17%) positive margins were found on US. Sensitivity, specificity, diagnostic accuracy, PPV and NPV of 44%, 94%, 80%, 73% and 82%, respectively, were found for specimen US. Specimen US represents a time and cost saving imaging tool for evaluating the presence of US detected-breast lesion within surgical specimen and for predicting the histological margin status.

Gallbladder Cancer: expert consensus statement

PubMed Central

Aloia, Thomas A; Járufe, Nicolas; Javle, Milind; Maithel, Shishir K; Roa, Juan C; Adsay, Volkan; Coimbra, Felipe J F; Jarnagin, William R

2015-01-01

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists was convened on 15 January 2014 to review current evidence on the management of gallbladder carcinoma in order to establish practice guidelines. In summary, within high incidence areas, the assessment of routine gallbladder specimens should include the microscopic evaluation of a minimum of three sections and the cystic duct margin; specimens with dysplasia or proven cancer should be extensively sampled. Provided the patient is medically fit for surgery, data support the resection of all gallbladder polyps of >1.0 cm in diameter and those with imaging evidence of vascular stalks. The minimum staging evaluation of patients with suspected or proven gallbladder cancer includes contrasted cross-sectional imaging and diagnostic laparoscopy. Adequate lymphadenectomy includes assessment of any suspicious regional nodes, evaluation of the aortocaval nodal basin, and a goal recovery of at least six nodes. Patients with confirmed metastases to N2 nodal stations do not benefit from radical resection and should receive systemic and/or palliative treatments. Primary resection of patients with early T-stage (T1b–2) disease should include en bloc resection of adjacent liver parenchyma. Patients with T1b, T2 or T3 disease that is incidentally identified in a cholecystectomy specimen should undergo re-resection unless this is contraindicated by advanced disease or poor performance status. Re-resection should include complete portal lymphadenectomy and bile duct resection only when needed to achieve a negative margin (R0) resection. Patients with preoperatively staged T3 or T4 N1 disease should be considered for clinical trials of neoadjuvant chemotherapy. Following R0 resection of T2–4 disease in N1 gallbladder cancer, patients should be considered for adjuvant systemic chemotherapy and/or chemoradiotherapy. PMID:26172135

Gallbladder cancer: expert consensus statement.

PubMed

Aloia, Thomas A; Járufe, Nicolas; Javle, Milind; Maithel, Shishir K; Roa, Juan C; Adsay, Volkan; Coimbra, Felipe J F; Jarnagin, William R

2015-08-01

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists was convened on 15 January 2014 to review current evidence on the management of gallbladder carcinoma in order to establish practice guidelines. In summary, within high incidence areas, the assessment of routine gallbladder specimens should include the microscopic evaluation of a minimum of three sections and the cystic duct margin; specimens with dysplasia or proven cancer should be extensively sampled. Provided the patient is medically fit for surgery, data support the resection of all gallbladder polyps of >1.0 cm in diameter and those with imaging evidence of vascular stalks. The minimum staging evaluation of patients with suspected or proven gallbladder cancer includes contrasted cross-sectional imaging and diagnostic laparoscopy. Adequate lymphadenectomy includes assessment of any suspicious regional nodes, evaluation of the aortocaval nodal basin, and a goal recovery of at least six nodes. Patients with confirmed metastases to N2 nodal stations do not benefit from radical resection and should receive systemic and/or palliative treatments. Primary resection of patients with early T-stage (T1b-2) disease should include en bloc resection of adjacent liver parenchyma. Patients with T1b, T2 or T3 disease that is incidentally identified in a cholecystectomy specimen should undergo re-resection unless this is contraindicated by advanced disease or poor performance status. Re-resection should include complete portal lymphadenectomy and bile duct resection only when needed to achieve a negative margin (R0) resection. Patients with preoperatively staged T3 or T4 N1 disease should be considered for clinical trials of neoadjuvant chemotherapy. Following R0 resection of T2-4 disease in N1 gallbladder cancer, patients should be considered for adjuvant systemic chemotherapy and/or chemoradiotherapy. © 2015 International Hepato-Pancreato-Biliary Association.

Optical see-through cancer vision goggles enable direct patient visualization and real-time fluorescence-guided oncologic surgery

PubMed Central

Mondal, Suman B.; Gao, Shengkui; Zhu, Nan; Hebimana-Griffin, LeMoyne; Akers, Walter J.; Liang, Rongguang; Gruev, Viktor; Margenthaler, Julie; Achilefu, Samuel

2017-01-01

Background The inability to directly visualize the patient and surgical site limits the use of current near infrared fluorescence-guided surgery systems for real-time sentinel lymph node biopsy and tumor margin assessment. Methods We evaluated an optical see-through goggle augmented imaging and navigation system (GAINS) for near-infrared fluorescence-guided surgery. Tumor-bearing mice injected with a near infrared cancer-targeting agent underwent fluorescence-guided tumor resection. Female Yorkshire pigs received hind leg intradermal indocyanine green injection and underwent fluorescence-guided popliteal lymph node resection. Four breast cancer patients received 99mTc-sulfur colloid and indocyanine green retroareolarly, before undergoing sentinel lymph node biopsy using radioactive tracking and fluorescence imaging. Three other breast cancer patients received indocyanine green retroareolarly before undergoing standard-of-care partial mastectomy, followed by fluorescence imaging of resected tumor and tumor cavity for margin assessment. Results Using near-infrared fluorescence from the dyes, the optical see-through GAINS accurately identified all mouse tumors, pig lymphatics, and 4 pig popliteal lymph nodes with high signal-to-background ratio. In 4 human breast cancer patients, 11 sentinel lymph nodes were identified with a detection sensitivity of 86.67± 0.27% for radioactive tracking and 100% for GAINS. Tumor margin status was accurately predicted by GAINS in all three patients, including clear margins in patients 1 and 2 and positive margins in patient 3 as confirmed by paraffin embedded section histopathology. Conclusions The optical see-through GAINS prototype enhances near infrared fluorescence-guided surgery for sentinel lymph node biopsy and tumor margin assessment in breast cancer patients without disrupting the surgical workflow in the operating room. PMID:28213790

PubMed Central

VICINI, C.; MONTEVECCHI, F.; D'AGOSTINO, G.; DE VITO, A.

2015-01-01

SUMMARY The primary goal of surgical oncology is to obtain a tumour resection with disease-free margins. Transoral robotic surgery (TORS) for surgical treatment of head-neck cancer is commensurate with standard treatments. However, the likelihood of positive margins after TORS is up to 20.2% in a recent US survey. The aim of this study is to evaluate the efficacy and the feasibility of narrow-band imaging (NBI) during TORS in order to improve the ability to achieve disease-free margins during tumour excision. The present study was conducted at the ENT, Head- Neck Surgery and Oral Surgery Unit, Department of Special Surgery, Morgagni Pierantoni Hospital, Azienda USL Romagna. From March 2008 to January 2015, 333 TORS were carried out for malignant and benign diseases. For the present study, we retrospectively evaluated 58 biopsy-proven squamous cell carcinoma patients who underwent TORS procedures. Patients were divided into 2 groups: (1) 32 who underwent TORS and intra-operative NBI evaluation (NBI-TORS); (2) 21 who underwent TORS with standard intra-operative white-light imaging (WLITORS). Frozen section analysis of margins on surgical specimens showed a higher rate of negative superficial lateral margins in the NBI-TORS group compared with the WLI-TORS group (87.9% vs. 57.9%, respectively, p = 0.02). The sensitivity and specificity of intra-operative use of NBI, respectively, were 72.5% and 66.7% with a negative predictive value of 87.9%. Tumour margin enhancement provided by NBI associated with magnification and 3-dimensional view of the surgical field might increase the capability to achieve an oncologically-safe resection in challenging anatomical areas where minimal curative resection is strongly recommended for function preservation. PMID:26246659

In vivo assessment of high-grade glioma biochemistry using microdialysis: a study of energy-related molecules, growth factors and cytokines.

PubMed

Marcus, Hani J; Carpenter, Keri L H; Price, Stephen J; Hutchinson, Peter J

2010-03-01

Microdialysis enables measurement of the chemistry of the cerebral extracellular fluid. This study's objective was to utilise microdialysis to monitor levels of glucose, lactate, pyruvate, glutamate and glycerol in patients following surgery for intrinsic brain tumours, and to assess the concentration of growth factors, cytokines and other proteins involved in the pathogenesis of high-grade gliomas in vivo. Eight patients with suspected high-grade gliomas were studied. Seven of these underwent resection with one microdialysis catheter placed at the tumour resection margin and, in six of these seven cases, a second microdialysis catheter in macroscopically normal peritumour tissue. The remaining glioma patient had an image-guided biopsy with a single catheter inserted stereotactically at the tumour margin. Histology demonstrated WHO IV glioblastoma in five cases, WHO III anaplastic astrocytoma in two cases, and one cerebral lymphoma. In the high-grade gliomas (WHO IV and III), tumour margin microdialysates consistently showed significantly lower glucose, higher lactate/pyruvate (L/P) ratio, higher glutamate and higher glycerol, relative to peritumour microdialysates (P < 0.05). These results indicate that malignant glioma margin tissue is metabolically extremely active. There was great variability in the microdialysate concentrations of growth factors (TGFalpha, EGF, VEGF), cytokines (IL-1alpha, IL-1beta, IL-1ra, IL-6, IL-8), matrix metalloproteinases (MMP-2, MMP-9) and their endogenous inhibitors (TIMP-1, TIMP-2). Notably, microdialysates from the glioma resection margin demonstrated significantly higher IL-8 concentration and higher MMP-2/TIMP-1 ratio when compared to peritumour microdialysates (P < 0.05), suggesting an environment favouring invasion and angiogenesis at the tumour margin. Microdialysis is a promising technique to study in vivo glioma metabolism, and may assist in the development of new therapies.

Optical See-Through Cancer Vision Goggles Enable Direct Patient Visualization and Real-Time Fluorescence-Guided Oncologic Surgery.

PubMed

Mondal, Suman B; Gao, Shengkui; Zhu, Nan; Habimana-Griffin, LeMoyne; Akers, Walter J; Liang, Rongguang; Gruev, Viktor; Margenthaler, Julie; Achilefu, Samuel

2017-07-01

The inability to visualize the patient and surgical site directly, limits the use of current near infrared fluorescence-guided surgery systems for real-time sentinel lymph node biopsy and tumor margin assessment. We evaluated an optical see-through goggle augmented imaging and navigation system (GAINS) for near-infrared, fluorescence-guided surgery. Tumor-bearing mice injected with a near infrared cancer-targeting agent underwent fluorescence-guided, tumor resection. Female Yorkshire pigs received hind leg intradermal indocyanine green injection and underwent fluorescence-guided, popliteal lymph node resection. Four breast cancer patients received 99m Tc-sulfur colloid and indocyanine green retroareolarly before undergoing sentinel lymph node biopsy using radioactive tracking and fluorescence imaging. Three other breast cancer patients received indocyanine green retroareolarly before undergoing standard-of-care partial mastectomy, followed by fluorescence imaging of resected tumor and tumor cavity for margin assessment. Using near-infrared fluorescence from the dyes, the optical see-through GAINS accurately identified all mouse tumors, pig lymphatics, and four pig popliteal lymph nodes with high signal-to-background ratio. In 4 human breast cancer patients, 11 sentinel lymph nodes were identified with a detection sensitivity of 86.67 ± 0.27% for radioactive tracking and 100% for GAINS. Tumor margin status was accurately predicted by GAINS in all three patients, including clear margins in patients 1 and 2 and positive margins in patient 3 as confirmed by paraffin-embedded section histopathology. The optical see-through GAINS prototype enhances near infrared fluorescence-guided surgery for sentinel lymph node biopsy and tumor margin assessment in breast cancer patients without disrupting the surgical workflow in the operating room.

Complete resection of a rectus abdominis muscle invaded by desmoid tumors and subsequent management with an abdominal binder: a case report.

PubMed

Ogawa, Tatsuhiko

2018-02-07

Desmoid-type fibromatosis is characterized by desmoid tumors, which are benign soft tissue tumors that can be locally aggressive but typically do not metastasize. Desmoid tumors can manifest anywhere in the body, and those in the abdominal cavity account for approximately 30 to 50% of all such tumors. Complete resection with free margins has been the standard treatment, but non-surgical therapies have been implemented recently. However, if tumors are strongly invasive and/or persistently recur, radical surgical resection with free margins remains the primary treatment. Unfortunately, radical resection may cause large abdominal defects and hinder reconstruction. Several reports and recommendations have addressed this issue; however, to the best of our knowledge, few reports have described complete resection and the subsequent reconstruction of the rectus abdominis muscle. A 35-year-old Asian woman presented at our hospital with a chief complaint of abdominal pain. She had abdominal desmoid tumors that required complete resection of her rectus abdominis muscle. Due to necrosis in her own reconstructed tissue, we failed to cover her anterior abdominal wall; thus, we used an abdominal binder as a substitute material to avoid exacerbating the incisional hernia and help her generate intra-abdominal pressure. This case report may be informative and helpful for the treatment of patients with desmoid tumors, as managing desmoid-type fibromatosis is difficult.

Multicolour versus monocolour inking specimens after pancreaticoduodenectomy for periampullary cancer: A single centre prospective randomised clinical trial.

PubMed

Casadei, Riccardo; Ricci, Claudio; Taffurelli, Giovanni; Pacilio, Carlo Alberto; Santini, Donatella; Di Marco, Mariacristina; Minni, Francesco

2018-03-01

R status represents an important prognostic factors in periampullary cancers. Thus, it is useful to verify if it can be influenced by different techniques of margination. Single-centre, randomised clinical trial of patients affected by periampullary cancer who underwent pancreaticoduodenectomies which included two different types of margination: arm A (multicolour inking) and arm B (monocolour inking). The primary endpoint was the overall R1 resection rate and its difference between the two arms. The secondary endpoints were the R1 resection rate in each margin and its difference between the two arms, and the impact of margin status on survival. Fifty patients were randomised, 41 analysed: 22 in arm A, 19 arm B. The overall R1 status was 61%, without significant differences between the two arms. The margin most commonly involved was the superior mesenteric artery (SMA) (36.6%). A trend in favour of arm B was shown for the superior mesenteric artery margin (arm A = 22.7% versus arm B = 52.6%; P = 0.060). The anterior surface (P = 0.015), SMA (P = 0.047) and pancreatic remnant (P = 0.018) margins significantly influenced disease-free survival. The R status was not influenced by different techniques of margination using a standardised pathological protocol. The SMA margin seemed to be the most important margin for evaluating both R status and disease-free survival. Copyright © 2018. Published by Elsevier Ltd.

Laparoscopic liver resection for malignancy: A review of the literature

PubMed Central

Alkhalili, Eyas; Berber, Eren

2014-01-01

AIM: To review the published literature about laparoscopic liver resection for malignancy. METHODS: A PubMed search was performed for original published studies until June 2013 and original series containing at least 30 patients were reviewed. RESULTS: All forms of hepatic resections have been described ranging from simple wedge resections to extended right or left hepatectomies. The usual approach is pure laparoscopic, but hand-assisted, as well as robotic approaches have been described. Most studies showed comparable results to open resection in terms of operative blood loss, postoperative morbidity and mortality. Many of them showed decreased postoperative pain, shorter hospital stays, and even lower costs. Oncological results including resection margin status and long-term survival were not inferior to open resection. CONCLUSION: In the hands of experienced surgeons, laparoscopic liver resection for malignant lesions is safe and offers some short-term advantages over open resection. Oncologically, similar survival rates have been observed in patients treated with the laparoscopic approach when compared to their open resection counterparts. PMID:25309091

Laparoscopic liver resection for malignancy: a review of the literature.

PubMed

Alkhalili, Eyas; Berber, Eren

2014-10-07

To review the published literature about laparoscopic liver resection for malignancy. A PubMed search was performed for original published studies until June 2013 and original series containing at least 30 patients were reviewed. All forms of hepatic resections have been described ranging from simple wedge resections to extended right or left hepatectomies. The usual approach is pure laparoscopic, but hand-assisted, as well as robotic approaches have been described. Most studies showed comparable results to open resection in terms of operative blood loss, postoperative morbidity and mortality. Many of them showed decreased postoperative pain, shorter hospital stays, and even lower costs. Oncological results including resection margin status and long-term survival were not inferior to open resection. In the hands of experienced surgeons, laparoscopic liver resection for malignant lesions is safe and offers some short-term advantages over open resection. Oncologically, similar survival rates have been observed in patients treated with the laparoscopic approach when compared to their open resection counterparts.

A Compressive Sensing Approach for Glioma Margin Delineation Using Mass Spectrometry

PubMed Central

Gholami, Behnood; Agar, Nathalie Y. R.; Jolesz, Ferenc A.; Haddad, Wassim M.; Tannenbaum, Allen R.

2013-01-01

Surgery, and specifically, tumor resection, is the primary treatment for most patients suffering from brain tumors. Medical imaging techniques, and in particular, magnetic resonance imaging are currently used in diagnosis as well as image-guided surgery procedures. However, studies show that computed tomography and magnetic resonance imaging fail to accurately identify the full extent of malignant brain tumors and their microscopic infiltration. Mass spectrometry is a well-known analytical technique used to identify molecules in a given sample based on their mass. In a recent study, it is proposed to use mass spectrometry as an intraoperative tool for discriminating tumor and non-tumor tissue. Integration of mass spectrometry with the resection module allows for tumor resection and immediate molecular analysis. In this paper, we propose a framework for tumor margin delineation using compressive sensing. Specifically, we show that the spatial distribution of tumor cell concentration can be efficiently reconstructed and updated using mass spectrometry information from the resected tissue. In addition, our proposed framework is model-free, and hence, requires no prior information of spatial distribution of the tumor cell concentration. PMID:22255629

Semi-Autonomous Electrosurgery for Tumor Resection Using a Multi-Degree of Freedom Electrosurgical Tool and Visual Servoing*

PubMed Central

Opfermann, Justin D.; Leonard, Simon; Decker, Ryan S.; Uebele, Nicholas A.; Bayne, Christopher E.; Joshi, Arjun S.; Krieger, Axel

2017-01-01

This paper specifies a surgical robot performing semi-autonomous electrosurgery for tumor resection and evaluates its accuracy using a visual servoing paradigm. We describe the design and integration of a novel, multi-degree of freedom electrosurgical tool for the smart tissue autonomous robot (STAR). Standardized line tests are executed to determine ideal cut parameters in three different types of porcine tissue. STAR is then programmed with the ideal cut setting for porcine tissue and compared against expert surgeons using open and laparoscopic techniques in a line cutting task. We conclude with a proof of concept demonstration using STAR to semi-autonomously resect pseudo-tumors in porcine tissue using visual servoing. When tasked to excise tumors with a consistent 4mm margin, STAR can semi-autonomously dissect tissue with an average margin of 3.67 mm and a standard deviation of 0.89mm. PMID:29503760

New technique of transanal proctectomy with completely robotic total mesorrectal excision for rectal cancer.

PubMed

Gómez Ruiz, Marcos; Palazuelos, Carlos Manuel; Martín Parra, José Ignacio; Alonso Martín, Joaquín; Cagigas Fernández, Carmen; del Castillo Diego, Julio; Gómez Fleitas, Manuel

2014-05-01

Anterior resection with total mesorectal excision is the standard method of rectal cancer resection. However, this procedure remains technically difficult in mid and low rectal cancer. A robotic transanal proctectomy with total mesorectal excision and laparoscopic assistance is reported in a 57 year old male with BMI 32 kg/m2 and rectal adenocarcinoma T2N1M0 at 5 cm from the dentate line. Operating time was 420 min. Postoperative hospital stay was 6 days and no complications were observed. Pathological report showed a 33 cm specimen with ypT2N0 adenocarcinoma at 2 cm from the distal margin, complete TME and non affected circumferential resection margin. Robotic technology might reduce some technical difficulties associated with TEM/TEO or SILS platforms in transanal total mesorectal excision. Further clinical trials will be necessary to assess this technique. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

Indocyanine Green Fluorescence Navigation Thoracoscopic Metastasectomy for Pulmonary Metastasis of Hepatocellular Carcinoma.

PubMed

Kawakita, Naoya; Takizawa, Hiromitsu; Kondo, Kazuya; Sakiyama, Shoji; Tangoku, Akira

2016-12-20

Indocyanine green can selectively accumulate in primary hepatocellular carcinoma (HCC) and extrahepatic metastases. We report a patient who underwent resection of pulmonary metastasis of HCC using a thoracoscopic near-infrared imaging system and fluorescent navigation surgery. A 66-year-old man with suspicion of pulmonary metastasis of HCC was referred to our hospital. Indocyanine green was injected intravenously at a dose of 0.5 mg/kg body weight, 20 h before thoracoscopic surgery. An endoscopic indocyanine green near-infrared fluorescence imaging system showed clear blue fluorescence, indicating pulmonary metastasis of HCC in a lingular segment. We performed wide wedge resection using the fluorescence image for navigation to confirm the surgical margins. The specimen was histologically confirmed as a pulmonary metastasis of HCC. In conclusion, thoracoscopic indocyanine green near-infrared fluorescence imaging for pulmonary metastases of HCC is useful in identifying tumor locations and ensuring resection margins.

Near-infrared autofluorescence spectroscopy of in vivo soft tissue sarcomas

PubMed Central

Nguyen, John Quan; Gowani, Zain; O'Connor, Maggie; Pence, Isaac; Nguyen, The-Quyen; Holt, Ginger; Mahadevan-Jansen, Anita

2016-01-01

Soft tissue sarcomas (STS) are a rare and heterogeneous group of malignant tumors that are often treated via surgical resection. Inadequate resection can lead to local recurrence and decreased survival rates. In this study, we investigate the hypothesis that near-infrared (NIR) autofluorescence can be utilized for tumor margin analysis by differentiating STS from the surrounding normal tissue. Intraoperative in vivo measurements were acquired from 30 patients undergoing STS resection and were characterized to differentiate between normal tissue and STS. Overall, normal muscle and fat were observed to have the highest and lowest autofluorescence intensities, respectively, with STS falling in between. With the exclusion of well-differentiated liposarcomas, the algorithm's accuracy for classifying muscle, fat, and STS was 93%, 92%, and 88%, respectively. These findings suggest that NIR autofluorescence spectroscopy has potential as a rapid and nondestructive surgical guidance tool that can inform surgeons of suspicious margins in need of immediate re-excision. PMID:26625035

Differentiating retroperitoneal liposarcoma tumors with optical coherence tomography

NASA Astrophysics Data System (ADS)

Lev, Dina; Baranov, Stepan A.; Carbajal, Esteban F.; Young, Eric D.; Pollock, Raphael E.; Larin, Kirill V.

2011-03-01

Liposarcoma (LS) is a rare and heterogeneous group of malignant mesenchymal neoplasms exhibiting characteristics of adipocytic differentiation. Currently, radical surgical resection represents the most effective and widely used therapy for patients with abdominal/retroperitoneal LS, but the presence of contiguous essential organs, such as the kidney, pancreas, spleen, adrenal glands, esophagus or colon, as well as often reoccurrence of LS in A/RP calls for the enhancement of surgical techniques to minimize resection and avoid LS reoccurrences. Difficulty in detecting the margins of neoplasms due to their affinity to healthy fat tissue accounts for the high reoccurrence of LS within A/RP. Nowadays, the microscopic detection of margins is possible only by use of biopsy, and the minimization of surgical resection of healthy tissues is challenging. In this presentation we'll demonstrate the initial OCT results for the imaging and distinction of LS and normal human fat tissues and clear detection of tumor boundaries.

A "conservative" method of thoracic wall dissection: a proposal for teaching human anatomy.

PubMed

Barberini, Fabrizio; Brunone, Francesca

2008-01-01

The common methods of dissection exposing the thoracic organs include crossing of the wall together with wide resection of its muscular planes. In order to preserve these structures, a little demolishing technique of the thoracic wall is proposed, entering the thoracic cavity without extensive resection of the pectoral muscles. This method is based on the fact that these muscles rise up from the wall, like a bridge connecting the costal plane with the upper limb, and that the pectoralis major shows a segmental constitution. SUPERIOR LIMIT: Resect the sternal manubrium transversely between the 1st and the 2nd rib. The incision is prolonged along the 1st intercostal space, separating the first sterno-costal segment of the pectoralis major from the second one, and involving the intercostal muscles as far as the medial margin of the pectoralis minor. This muscle must be raised up, and the transverse resection continued below its medial margin latero-medially along the 1st intercostal space, to rejoin the cut performed before. Then, the incision of the 1st intercostal space is prolonged below the lateral margin of the pectoralis minor, which must be kept raised up, medio-laterally as far as the anterior axillary line. INFERIOR LIMIT: It corresponds to the inferior border of the thoracic cage, resected from the xiphoid process to the anterior axillary line, together with the sterno-costal insertions of the diaphragm. Then, an incision of the sterno-pericardial ligaments and a median sternotomy from the xiphoid process to the transverse resection of the manubrium should be performed. LATERAL LIMIT: From the point of crossing of the anterior axillary line with the inferior limit, resect the ribs from the 10th to the 2nd one. The lateral part of the pectoralis major must be raised up, so that the costal resection may be continued below it. Then, at the lateral extremity of the superior incision, the first and the second sternocostal segment of the pectoralis major must be divaricated, to resect the 2nd and the 3rd rib. It is helpful increasing the distance between pectoralis major and thoracic wall by adducing the arm on the chest. Finally, open the two halves of the thoracic wall, like shutters of a window rotating on the hinges, formed by the non-resected intercostal muscles and by the intercostal portions of the serratus anterior, along the anterior axillary line.

[Efficacy analysis of proximally extended resection for locally advanced rectal cancer after neoadjuvant chemoradiotherapy].

PubMed

Qin, Qiyuan; Kuang, Yingyi; Ma, Tenghui; Wu, Yali; Wang, Huaiming; Pi, Yanna; Wang, Hui; Wang, Lei

2017-11-25

To evaluate the short-term outcomes and perioperative safety of proximally extended resection for locally advanced rectal cancer after neoadjuvant chemoradiotherapy. From colorectal cancer database in The Sixth Affiliated Hospital of Sun Yat-sen University, a cohort of patients who underwent neoadjuvant chemoradiotherapy(1.8-2.0 Gy per day, 25-28 fractions, concurrent fluorouracil-based chemotherapy) followed by curative sphincter-preserving surgery for locally advanced rectal cancer between May 2016 and June 2017 were retrospectively identified. Exclusion criteria were synchronous colon cancer, intraoperatively confirmed distal metastasis, multiple visceral resection, and emergency operation. Thirty-one patients underwent proximal extended resection and two were excluded for incomplete extended resection, then 29 patients were enrolled as the extended group. Using propensity scores matching with 1/1 ration, 29 locally advanced rectal cancer patients who underwent conventional resection after neoadjuvant chemoradiotherapy at the same time were matched as the conventional group. Clinical data of two groups were analyzed, and the baseline characteristics and short-term outcomes were compared using the t test, χ 2 test, or Mann-Whitney U test. Two groups were well balanced with respect to the baseline characteristics after propensity score matching. As compared with conventional group, patients in extended group had longer surgical specimen [(18.8±5.1) cm vs.(11.6±3.4) cm, t=6.314, P=0.000] and longer proximal resection margin [(14.8±5.5) cm vs.(8.2±3.0) cm, t=5.725, P=0.000], but also had longer total operating time [(322.4±100.7) min vs.(254.6±70.3) min, t=2.975, P=0.004] and more intraoperative blood loss [100(225) ml vs. 100(50) ml, Z=-2.403, P=0.016]. No significant differences were observed in the length of distal resection margin, ratio of positive resection margin, number of retrieved lymph node, time of analgesic use, time of draining tube use, time to first flatus, time to first oral diet, and postoperative hospital stay. During the perioperative period of 30 days, the morbidity of complication in extended group and conventional group was 17.2%(5/29) and 34.5% (10/29), respectively (P=0.134). Proximally extended resection is a radical and safe surgical alternative for locally advanced rectal cancer after neoadjuvant chemoradiotherapy, which can potentially reduce the risk of anastomosis complication.

Long-term outcomes in primary spinal osteochondroma: a multicenter study of 27 patients

PubMed Central

Sciubba, Daniel M.; Macki, Mohamed; Bydon, Mohamad; Germscheid, Niccole M.; Wolinsky, Jean-Paul; Boriani, Stefano; Bettegowda, Chetan; Chou, Dean; Luzzati, Alessandro; Reynolds, Jeremy J.; Szövérfi, Zsolt; Zadnik, Patti; Rhines, Laurence D.; Gokaslan, Ziya L.; Fisher, Charles G.; Varga, Peter Paul

2016-01-01

OBJECT Clinical outcomes in patients with primary spinal osteochondromas are limited to small series and sporadic case reports. The authors present data on the first long-term investigation of spinal osteochondroma cases. METHODS An international, multicenter ambispective study on primary spinal osteochondroma was performed. Patients were included if they were diagnosed with an osteochondroma of the spine and received surgical treatment between October 1996 and June 2012 with at least 1 follow-up. Perioperative prognostic variables, including patient age, tumor size, spinal level, and resection, were analyzed in reference to long-term local recurrence and survival. Tumor resections were compared using Enneking appropriate (EA) or Enneking inappropriate surgical margins. RESULTS Osteochondromas were diagnosed in 27 patients at an average age of 37 years. Twenty-two lesions were found in the mobile spine (cervical, thoracic, or lumbar) and 5 in the fixed spine (sacrum). Twenty-three cases (88%) were benign tumors (Enneking tumor Stages 1–3), whereas 3 (12%) exhibited malignant changes (Enneking tumor Stages IA–IIB). Sixteen patients (62%) underwent en bloc treatment—that is, wide or marginal resection—and 10 (38%) underwent intralesional resection. Twenty-four operations (92%) followed EA margins. No one received adjuvant therapy. Two patients (8%) experienced recurrences: one in the fixed spine and one in the mobile spine. Both recurrences occurred in latent Stage 1 tumors following en bloc resection. No osteochondroma-related deaths were observed. CONCLUSIONS In the present study, most patients underwent en bloc resection and were treated as EA cases. Both recurrences occurred in the Stage 1 tumor cohort. Therefore, although benign in character, osteochondromas still require careful management and thorough follow-up. PMID:25793467

Current Dosing Paradigm for Stereotactic Radiosurgery Alone After Surgical Resection of Brain Metastases Needs to Be Optimized for Improved Local Control

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

Prabhu, Roshan; Shu, Hui-Kuo; Winship Cancer Institute, Emory University, Atlanta, GA

2012-05-01

Purpose: To describe the use of radiosurgery (RS) alone to the resection cavity after resection of brain metastases as an alternative to adjuvant whole-brain radiotherapy (WBRT). Methods and Materials: Sixty-two patients with 64 cavities were treated with linear accelerator-based RS alone to the resection cavity after surgical removal of brain metastases between March 2007 and August 2010. Fifty-two patients (81%) had a gross total resection. Median cavity volume was 8.5 cm{sup 3}. Forty-four patients (71%) had a single metastasis. Median marginal and maximum doses were 18 Gy and 20.4 Gy, respectively. Sixty-one cavities (95%) had gross tumor volume to planningmore » target volume expansion of {>=}1 mm. Results: Six-month and 1-year actuarial local recurrence rates were 14% and 22%, respectively, with a median follow-up period of 9.7 months. Six-month and 1-year actuarial distant brain recurrence, total intracranial recurrence, and freedom from WBRT rates were 31% and 51%, 41% and 63%, and 91% and 74%, respectively. The symptomatic cavity radiation necrosis rate was 8%, with 2 patients (3%) undergoing surgery. Of the 11 local failures, 8 were in-field, 1 was marginal, and 2 were both (defined as in-field if {>=}90% of recurrence within the prescription isodose and marginal if {>=}90% outside of the prescription isodose). Conclusions: The high rate of in-field cavity failure suggests that geographic misses with highly conformal RS are not a major contributor to local recurrence. The current dosing regimen derived from Radiation Therapy Oncology Group protocol 90-05 should be optimized in this patient population before any direct comparison with WBRT.« less

High- and low-dose-rate intraoperative radiotherapy for thoracic malignancies resected with close or positive margins.

PubMed

Fleming, Christopher; Rimner, Andreas; Cohen, Gil'ad N; Woo, Kaitlin M; Zhang, Zhigang; Rosenzweig, Kenneth E; Alektiar, Kaled M; Zelefsky, Michael J; Bains, Manjit S; Wu, Abraham J

2016-01-01

Local recurrence is a significant problem after surgical resection of thoracic tumors. As intraoperative radiotherapy (IORT) can deliver radiation directly to the threatened margin, we have used this therapy in an attempt to reduce local recurrence, using high-dose-rate (HDR) as well as low-dose-rate (LDR) techniques. We performed a retrospective review of patients undergoing LDR ((125)I) mesh placement or HDR ((192)Ir) afterloading therapy during lung tumor resection between 2001 and 2013 at our institution. Competing risks methods were used to estimate the cumulative incidence of local failure. We also assessed possible predictive factors of local failure. Fifty-nine procedures (41 LDR and 18 HDR) were performed on 58 patients. Median follow-up was 55.1 months. Cumulative incidence of local failure at 1, 2, and 3 years was 28.5%, 34.2%, and 34.2%, respectively. Median overall survival was 39.9 months. There was no significant difference in local failure according to margin status, HDR vs. LDR, use of adjuvant external beam radiotherapy, or metastatic vs. primary tumor. Two patients (3.4%) experienced Grade 3+ toxicities likely related to brachytherapy. Additionally, 7 patients experienced Grade 3+ postsurgical complications unlikely related to brachytherapy. IORT is associated with good local control after resection of thoracic tumors otherwise at very high risk for local recurrence. There is a low incidence of severe toxicity attributable to brachytherapy. HDR-IORT appears to have equivalent outcomes to LDR-IORT. HDR or LDR-IORT can, therefore, be considered in situations where the oncologic completeness of thoracic tumor resection is in doubt. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Salvage Surgery for Locoregional Failure in Anal Squamous Cell Carcinoma.

PubMed

Guerra, Glen R; Kong, Joseph C; Bernardi, Maria-Pia; Ramsay, Robert G; Phillips, Wayne A; Warrier, Satish K; Lynch, A Craig; Ngan, Samuel Y; Heriot, Alexander G

2018-02-01

Anal squamous cell carcinoma is a rare cancer with a high cure rate, making research into the treatment of locoregional failure difficult. The purpose of this study was to examine factors related to local treatment failure and determine the outcomes of patients undergoing local salvage resection. This was a retrospective cohort study. This study was conducted at a quaternary referral center. Patients with anal squamous cell carcinoma treated with chemoradiotherapy between January 1983 and December 2015 were included. The influence of patient-, tumor-, and treatment-related factors on the primary outcome measures of locoregional failure, overall survival, and disease-free survival were investigated. Of 467 patients with anal squamous cell carcinoma, 63 experienced locoregional failure with 41 undergoing salvage resection. Twenty-seven patients (38%) had persistent disease and 36 (62%) developed locoregional recurrence. Multivariate analysis identified tumor stage (HR, 3.16; p < 0.002) as an independent predictor of locoregional failure. Thirty abdominoperineal resections and 11 pelvic exenterations were undertaken with no surgical mortality. At a median follow-up of 20 months (range, 4-150 months), 5-year overall and disease-free survival for the salvage cohort was 51% and 47%. Margin positivity was an independent predictor for relapse post-salvage surgery on multivariate analysis (HR, 20.1; p = 0.027). Nineteen patients (48%) developed further relapse, which included all 10 patients with a positive resection margin, 3 of whom underwent re-resection. Of the 19 patients with relapse, 3 remain alive and 2 have persistent disease. Limitations include the retrospective nature of the database, the prolonged time period of the study, and episodes of incomplete data. Advanced T stage is an independent predictor of local failure in anal squamous cell carcinoma. Most patients can be salvaged, with a positive resection margin being a strong predictor of further relapse and poor outcome. See Video Abstract at http://links.lww.com/DCR/A515.

Improvement of surgical margin with a coupled saline-radio-frequency device for multiple colorectal liver metastases.

PubMed

Ogata, Satoshi; Kianmanesh, Reza; Varma, Deepak; Belghiti, Jacques

2005-01-01

Complete resection of colorectal liver metastases (LM) has been the only curative treatment. However, when LM are multiple and bilobar, only a few patients are candidates for curative surgery. We report on a 53-year-old woman with synchronous multiple and bilobar LM from sigmoidal cancer who became resectable after a multimodal strategy including preoperative systemic chemotherapy and two-step surgery. The spectacular decrease in tumor size after systemic chemotherapy led us to perform two-step surgery, including right portal-vein ligation and left liver metastasectomies, with a coupled saline-radiofrequency device, in order to improve the surgical margin. An extended right hepatectomy was performed later to remove the remaining right liver lesions. The patient was discharged after 28 days without major complication and was recurrence-free 14 months later. We conclude that improving the surgical margin with a coupled saline-radiofrequency device is feasible and effective, avoiding small remnant liver even after multiple tumorectomies. The multimodal strategy, including preoperative chemotherapy, two-step surgery, and tumorectomies, using a coupled saline-radiofrequency device, could increase the number of patients with diffuse bilobar liver metastases who can benefit from liver resection.

Changes in Sunken Eyes Combined with Blepharoptosis after Levator Resection.

PubMed

Mawatari, Yuki; Fukushima, Mikiko; Kawaji, Takahiro

2017-12-01

This study aims to report the changes in sunken eyes combined with blepharoptosis after levator resection. Analysis involved 60 eyes from 32 patients with sunken eyes combined with blepharoptosis. Advancement of the levator aponeurosis and the Müller's muscle complex (levator resection) was performed in these patients. Area of upper eyelid sulcus (AES) was defined as the area of the upper eyelid shadow. The digital images were converted to black and white using image-processing software (Adobe Photoshop), and the AES was calculated using ImageJ software. In addition, margin reflex distance, eyebrow height (EBH), and AES were measured before and 3 months after surgery to assess the changes in the eyelids. Preoperative AES was significantly correlated to age ( P < 0.0001; r = 0.8062). Sunken eyes were remarkably improved after levator resection in all patients. Mean margin reflex distance significantly increased, whereas mean EBH and mean AES significantly decreased at 3 months after surgery ( P < 0.0001). The AES change was significantly correlated to the EBH change ( P < 0.0001; r = 0.5184). The principal aim of levator resection is to improve upper eyelid height and visual fields; however, this technique can alter the location of the eyebrow and upper orbital fat. The effects fill the hollowness of the upper eyelid and can remarkably improve sunken eyes.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma

PubMed Central

Benekli, Mustafa; Unal, Olcun Umit; Unek, İlkay Tugba; Tastekin, Didem; Dane, Faysal; Algın, Efnan; Ulger, Sukran; Eren, Tulay; Topcu, Turkan Ozturk; Turkmen, Esma; Babacan, Nalan Akgül; Tufan, Gulnihal; Urakci, Zuhat; Ustaalioglu, Basak Oven; Uysal, Ozlem Sonmez; Ercelep, Ozlem Balvan; Taskoylu, Burcu Yapar; Aksoy, Asude; Canhoroz, Mustafa; Demirci, Umut; Dogan, Erkan; Berk, Veli; Balakan, Ozan; Ekinci, Ahmet Şiyar; Uysal, Mukremin; Petekkaya, İbrahim; Ozturk, Selçuk Cemil; Tonyalı, Önder; Çetin, Bülent; Aldemir, Mehmet Naci; Helvacı, Kaan; Ozdemir, Nuriye; Oztop, İlhan; Coskun, Ugur; Uner, Aytug; Ozet, Ahmet; Buyukberber, Suleyman

2015-01-01

Background We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). Methods A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. Results Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. Conclusions Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection. PMID:26361410

Role of specimen US for predicting resection margin status in breast conserving therapy

PubMed Central

MOSCHETTA, M.; TELEGRAFO, M.; INTRONA, T.; COI, L.; RELLA, L.; RANIERI, V.; CIRILLI, A.; IANORA, A.A. STABILE; ANGELELLI, G.

2015-01-01

Aim To assess the diagnostic accuracy of specimen ultrasound (US) for predicting resection margin status in women undergoing breast conserving therapy for US-detected cancer, having the histological findings as the reference standard. Patients and methods A total of 132 consecutive patients (age range, 34–87 years; mean, 51 years) underwent breast-conserving surgery for US-detected invasive breast cancer. All surgical specimens underwent US examination. The presence of lesion within the specimen and its distance from the specimen margins were assessed considering a threshold distance between the lesion and specimen margins of 10 mm. US findings were then compared with the pathological ones and specimen US. Sensitivity, specificity, diagnostic accuracy, positive (PPV) and negative predictive values (NPV) for predicting histological margin status were evaluated, having the histological findings as the reference standard. Results The histological examination detected invasive ductal carcinoma in 96/132 (73%) cases, invasive lobular carcinoma in 32/132 (24%), mucinous carcinoma in 4/132 (3%). The pathological margin analysis revealed 96/132 (73%) negative margins and 36 (27%) close/positive margins. US examination detected all 132 breast lesions within the surgical specimens. 110 (83%) negative margins and 22 (17%) positive margins were found on US. Sensitivity, specificity, diagnostic accuracy, PPV and NPV of 44%, 94%, 80%, 73% and 82%, respectively, were found for specimen US. Conclusions Specimen US represents a time and cost saving imaging tool for evaluating the presence of US detected-breast lesion within surgical specimen and for predicting the histological margin status. PMID:26712255

Cryo-Assisted Resection En Bloc, and Cryoablation In Situ, of Primary Breast Cancer Coupled With Intraoperative Ultrasound-Guided Tracer Injection: A Preliminary Clinical Study.

PubMed

Korpan, Nikolai N; Xu, Kecheng; Schwarzinger, Philipp; Watanabe, Masashi; Breitenecker, Gerhard; Patrick, Le Pivert

2018-01-01

The aim of the study was to perform cryosurgery on a primary breast tumor, coupled with simultaneous peritumoral and intratumoral tracer injection of a blue dye, to evaluate lymphatic mapping. We explored the ability of our strategy to prevent tumor cells, but not that of injected tracers, to migrate to the lymphovascular drainage during conventional resection of frozen breast malignancies. Seventeen patients aged 51 (14) years (mean [standard deviation]), presenting primary breast cancer with stage I to IV, were randomly selected and treated in The Rudolfinerhaus Private Clinic in Vienna, Austria, and included in this preliminary clinical study. Under intraoperative ultrasound, 14 patients underwent curative cryo-assisted tumor resection en bloc, coupled with peritumoral tracer injection, which consisted of complete tumor freezing and concomitant peritumor injection with a blue dye, before resection and sentinel lymph node dissection (group A). Group B consists of 3 patients previously refused any standard therapy and had palliative tumor cryoablation in situ combined with intratumoral tracer injection. The intraoperative ultrasound facilitated needle positioning and dye injection timing. In group A, the frozen site extruded the dye that was distributed through the unfrozen tumor, the breast tissue, and the resection cavity for 12 patients. One to 4 lymph nodes were stained for 10 of 14 patients. The resection margin was evaluable. Our intraoperative ultrasound-guided performance revealed the injection and migration of a blue dye during the frozen resection en bloc and cryoablation in situ of primary breast tumors. Sentinel lymph node mapping, pathological determination of the tumor, and resection margins were achievable. The study paves the way for intraoperative cryo-assisted therapeutic strategies for breast cancer.

Overall survival after resection of retroperitoneal sarcoma at academic cancer centers versus community cancer centers: An analysis of the National Cancer Data Base.

PubMed

Berger, Nicholas G; Silva, Jack P; Mogal, Harveshp; Clarke, Callisia N; Bedi, Manpreet; Charlson, John; Christians, Kathleen K; Tsai, Susan; Gamblin, T Clark

2018-02-01

Operative resection remains the definitive curative therapy for retroperitoneal sarcoma. Data published recently show a correlation between improved outcomes for complex oncologic operations and treatment at academic centers. For large retroperitoneal sarcomas, operative resection can be complex and require multidisciplinary care. We hypothesized that survival rates vary between type of treating center for patients undergoing resection for retroperitoneal sarcoma. Patients with stage I to III nonmetastatic retroperitoneal sarcomas who underwent operative resection were identified from the National Cancer Database during the years 2004-2013. Treating centers were categorized as academic cancer centers or community cancer centers. Overall survival was analyzed by log-rank test and graphed using Kaplan-Meier method. A total of 2,762 patients were identified. A majority of patients (59.4%, n = 1,642) underwent resection at an academic cancer centers. Median age at diagnosis was 63 years old. Neoadjuvant radiotherapy was more common at academic cancer centers, while adjuvant radiotherapy was more common at community cancer centers. Improved overall survival was seen at academic cancer centers across all stages compared with community cancer centers (P = .014) but, after multivariable Cox regression analysis, was not a significant independent predictor of survival (hazard ratio = 0.91, 95% confidence interval, 0.79-1.04, P = .171). Academic cancer centers exhibited a greater rate of R0 resection (55.9% vs 47.0%, P < .001) and a lesser odds of positive margins (odds ratio 0.83, 95% confidence interval, 0.69-0.99, P = .044) after multivariable logistic regression. Resection for retroperitoneal sarcoma performed at academic cancer centers was an independent predictor of margin-negative resection but was not a statistically significant factor for survival. This observation suggests that site of care may contribute to some aspect of improved oncologic resection for retroperitoneal sarcoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Designing a wearable navigation system for image-guided cancer resection surgery

PubMed Central

Shao, Pengfei; Ding, Houzhu; Wang, Jinkun; Liu, Peng; Ling, Qiang; Chen, Jiayu; Xu, Junbin; Zhang, Shiwu; Xu, Ronald

2015-01-01

A wearable surgical navigation system is developed for intraoperative imaging of surgical margin in cancer resection surgery. The system consists of an excitation light source, a monochromatic CCD camera, a host computer, and a wearable headset unit in either of the following two modes: head-mounted display (HMD) and Google glass. In the HMD mode, a CMOS camera is installed on a personal cinema system to capture the surgical scene in real-time and transmit the image to the host computer through a USB port. In the Google glass mode, a wireless connection is established between the glass and the host computer for image acquisition and data transport tasks. A software program is written in Python to call OpenCV functions for image calibration, co-registration, fusion, and display with augmented reality. The imaging performance of the surgical navigation system is characterized in a tumor simulating phantom. Image-guided surgical resection is demonstrated in an ex vivo tissue model. Surgical margins identified by the wearable navigation system are co-incident with those acquired by a standard small animal imaging system, indicating the technical feasibility for intraoperative surgical margin detection. The proposed surgical navigation system combines the sensitivity and specificity of a fluorescence imaging system and the mobility of a wearable goggle. It can be potentially used by a surgeon to identify the residual tumor foci and reduce the risk of recurrent diseases without interfering with the regular resection procedure. PMID:24980159

Designing a wearable navigation system for image-guided cancer resection surgery.

PubMed

Shao, Pengfei; Ding, Houzhu; Wang, Jinkun; Liu, Peng; Ling, Qiang; Chen, Jiayu; Xu, Junbin; Zhang, Shiwu; Xu, Ronald

2014-11-01

A wearable surgical navigation system is developed for intraoperative imaging of surgical margin in cancer resection surgery. The system consists of an excitation light source, a monochromatic CCD camera, a host computer, and a wearable headset unit in either of the following two modes: head-mounted display (HMD) and Google glass. In the HMD mode, a CMOS camera is installed on a personal cinema system to capture the surgical scene in real-time and transmit the image to the host computer through a USB port. In the Google glass mode, a wireless connection is established between the glass and the host computer for image acquisition and data transport tasks. A software program is written in Python to call OpenCV functions for image calibration, co-registration, fusion, and display with augmented reality. The imaging performance of the surgical navigation system is characterized in a tumor simulating phantom. Image-guided surgical resection is demonstrated in an ex vivo tissue model. Surgical margins identified by the wearable navigation system are co-incident with those acquired by a standard small animal imaging system, indicating the technical feasibility for intraoperative surgical margin detection. The proposed surgical navigation system combines the sensitivity and specificity of a fluorescence imaging system and the mobility of a wearable goggle. It can be potentially used by a surgeon to identify the residual tumor foci and reduce the risk of recurrent diseases without interfering with the regular resection procedure.

[Strategy of liver resection during chemotherapy for otherwise unresectable colorectal metastases].

PubMed

Tanaka, Kuniya; Kumamoto, Takafumi; Takeda, Kazuhisa; Nojiri, Kazunori; Endo, Itaru

2013-07-01

With multidisciplinary management of patients with effective chemotherapy that can downstage metastases, more patients with previously inoperable disease can benefit from surgery. Surgery in isolation may be approaching technical limits, but now is likely to help more patients because of success of complementary strategies, particularly newer chemotherapy and targeted therapy. Leaving behind disappearing metastases after chemotherapy, margin-positive resection, staged liver resection, and liver-first reversed management permit potentially curative surgery for patients previously unable to survive resection. Further, survival benefit from maximum debulking surgery, like ovarian cancer, for colorectal liver metastases is uncertain at present, but likely. Individualized multidisciplinary treatment planning using such strategies is essential.

Mandibular angle resection and masticatory muscle hypertrophy - a technical note and morphological optimization.

PubMed

Andreishchev, A R; Nicot, R; Ferri, J

2014-11-01

Mandibular angle resection is rarely used, but is a highly effective means of correcting facial defects. We report a mandibular angle resection technique associated with the removal of a part of hypertrophic masseter muscles and resection of buccal fat pad. Anatomical reminders: the most important entities are the facial artery and vein, crossing the lower margin of the jaw just in front of the anterior boarder of the masseter muscle and the temporomaxillary vein, passing through the temporomaxillary fossa; preoperative aspects: the preoperative examination included a radiological assessment of the shape and size of the mandibular angle; surgical technique: an intra-oral approach was usually used. The most effective and convenient method for the osteotomy was using a reciprocating saw. This technique allowed achieving a smooth contour of masseter muscles during masticatory movements or at rest. Eleven mandibular angle resections were performed from 2001 to 2009. The surgery was supplemented by remodeling the lower margin of the jaw for 5 other patients. No permanent facial palsy was noted. One patient presented a unilateral long-term loss of sensitivity of the lower lip and chin. This surgical technique if simple even requires using good technical equipment, and observing a set of rules. Using these principles allows simplifying the surgical technique, and decreasing its morbidity. A part of the masseter muscles and the buccal fat pad can sometimes be resected to improve the morphological results. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A multiplanar complex resection of a low-grade chondrosarcoma of the distal femur guided by K-wires previously inserted under CT-guide: a case report.

PubMed

Zoccali, Carmine; Rossi, Barbara; Ferraresi, Virginia; Anelli, Vincenzo; Rita, Alessandro

2014-08-13

In muscular skeletal oncology aiming to achieve wide surgical margin is one of the main factors influencing patient prognosis. In cases where lesions are either meta or epiphyseal, surgery most often compromises joint integrity and stability because muscles, tendons and ligaments are involved in wide resection. When lesions are well circumscribed they can be completely resected by performing multi-planar osteotomies guided by computer-assisted navigation. We describe a case of low-grade chondrosarcoma of the distal femur where a simple but effective technique was useful to perform complex multiplanar osteotomies. No similar techniques are reported in the literature. A 57 year-old Caucasian female was referred to our department for the presence of a distal femur chondrosarcoma. A resection with the presenting technique was scheduled. The first step consists of inserting several K-wires under CT-scan control to delimitate the tumor; the second step consists of tumor removal: in operative theatre, following surgical access, k-wires are used as guide positioning; scalpels are externally placed to k-wires to perform a safe osteotomy. Computed assisted resections can be considered the most advantageous method to reach the best surgical outcome; unfortunately navigation systems are only available in specialized centres. The present technique allows for a multiplanar complex resection when navigation systems are not available. This technique can be applied in low-grade tumours where a minimal wide margin can be considered sufficient.

Adjuvant Gemcitabine and Gemcitabine-based Chemoradiotherapy Versus Gemcitabine Alone After Pancreatic Cancer Resection: The Indiana University Experience.

PubMed

Khawaja, Muhammad R; Kleyman, Svetlana; Yu, Zhangsheng; Howard, Thomas; Burns, Matthew; Nakeeb, Attila; Loehrer, Patrick J; Cardenes, Higinia R; Chiorean, Elena Gabriela

2017-02-01

Adjuvant therapy after surgical resection is the current standard for pancreatic adenocarcinoma; however, the role of chemoradiotherapy (CRT) remains unclear. This study was conducted to compare the efficacy outcomes with adjuvant gemcitabine and gemcitabine-based CRT (CT-CRT) versus gemcitabine chemotherapy (CT) alone after pancreaticoduodenectomy. Among 165 patients who underwent surgical resection for pancreatic cancer at Indiana University Medical Center between 2004 and 2008, we retrospectively identified 53 consecutive patients who received adjuvant therapy (CT-CRT=34 patients; CT=19 patients) and had adequate follow-up medical records. The median follow-up was 19.1 months. Median disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier method, and a Cox-regression model was used to compare survival outcomes after adjusting for age, status of resection margins, and lymph node involvement. The OS for the CT-CRT group was significantly higher compared with the CT group (median, 20.4 vs. 16.6 mo; hazard ratio, 2.42; 95% CI, 1.17-5.01). The median DFS for the CT-CRT group was 13.7 versus 11.1 months for the CT group (hazard ratio, 2.88; 95% CI, 1.37-6.06). On subgroup analyses, significantly superior OS and DFS were observed among patients younger than 65 years, T3/T4 tumor stage, negative resection margins, and positive lymph node involvement. Gemcitabine plus gemcitabine-based CRT compared with gemcitabine alone leads to superior DFS and OS for patients with resected pancreatic cancer.

Properties of the recombinant TNF-binding proteins from variola, monkeypox, and cowpox viruses are different.

PubMed

Gileva, Irina P; Nepomnyashchikh, Tatiana S; Antonets, Denis V; Lebedev, Leonid R; Kochneva, Galina V; Grazhdantseva, Antonina V; Shchelkunov, Sergei N

2006-11-01

Tumor necrosis factor (TNF), a potent proinflammatory and antiviral cytokine, is a critical extracellular immune regulator targeted by poxviruses through the activity of virus-encoded family of TNF-binding proteins (CrmB, CrmC, CrmD, and CrmE). The only TNF-binding protein from variola virus (VARV), the causative agent of smallpox, infecting exclusively humans, is CrmB. Here we have aligned the amino acid sequences of CrmB proteins from 10 VARV, 14 cowpox virus (CPXV), and 22 monkeypox virus (MPXV) strains. Sequence analyses demonstrated a high homology of these proteins. The regions homologous to cd00185 domain of the TNF receptor family, determining the specificity of ligand-receptor binding, were found in the sequences of CrmB proteins. In addition, a comparative analysis of the C-terminal SECRET domain sequences of CrmB proteins was performed. The differences in the amino acid sequences of these domains characteristic of each particular orthopoxvirus species were detected. It was assumed that the species-specific distinctions between the CrmB proteins might underlie the differences in these physicochemical and biological properties. The individual recombinant proteins VARV-CrmB, MPXV-CrmB, and CPXV-CrmB were synthesized in a baculovirus expression system in insect cells and isolated. Purified VARV-CrmB was detectable as a dimer with a molecular weight of 90 kDa, while MPXV- and CPXV-CrmBs, as monomers when fractioned by non-reducing SDS-PAGE. The CrmB proteins of VARV, MPXV, and CPXV differed in the efficiencies of inhibition of the cytotoxic effects of human, mouse, or rabbit TNFs in L929 mouse fibroblast cell line. Testing of CrmBs in the experimental model of LPS-induced shock using SPF BALB/c mice detected a pronounced protective effect of VARV-CrmB. Thus, our data demonstrated the difference in anti-TNF activities of VARV-, MPXV-, and CPXV-CrmBs and efficiency of VARV-CrmB rather than CPXV- or MPXV-CrmBs against LPS-induced mortality in mice.

Coblation-assisted endonasal endoscopic resection of juvenile nasopharyngeal angiofibroma.

PubMed

Ye, L; Zhou, X; Li, J; Jin, J

2011-09-01

Juvenile nasopharyngeal angiofibroma may be successfully resected using endoscopic techniques. However, the use of coblation technology for such resection has not been described. This study aimed to document cases of Fisch class I juvenile nasopharyngeal angiofibroma with limited nasopharyngeal and nasal cavity extension, which were completely resected using an endoscopic coblation technique. We retrospectively studied 23 patients with juvenile nasopharyngeal angiofibroma who underwent resection with either traditional endoscopic instruments (n = 12) or coblation (n = 11). Intra-operative blood loss and overall operative time were recorded. The mean tumour resection time for coblation and traditional endoscopic instruments was 87 and 136 minutes, respectively (t = 9.962, p < 0.001). Mean intra-operative blood loss was 121 and 420 ml, respectively (t = 28.944, p < 0.001), a significant difference. Both techniques achieved complete tumour resection with minimal damage to adjacent tissues, and no recurrence in any patient. Coblation successfully achieves transnasal endoscopic resection of juvenile nasopharyngeal angiofibroma (Fisch class I), with good surgical margins and minimal blood loss.

Risk analysis factors for local recurrence in Ewing's sarcoma: when should adjuvant radiotherapy be administered?

PubMed

Albergo, J I; Gaston, C L L; Parry, M C; Laitinen, M K; Jeys, L M; Tillman, R M; Abudu, A T; Grimer, R J

2018-02-01

The aim of this study was to analyse a group of patients with non-metastatic Ewing's sarcoma at presentation and identify prognostic factors affecting the development of local recurrence, in order to assess the role of radiotherapy. A retrospective review of all patients with a Ewing's sarcoma treated between 1980 and 2012 was carried out. Only those treated with chemotherapy followed by surgery and/or radiotherapy were included. Patients were grouped according to site (central or limb) for further analysis of the prognostic factors. A total of 388 patients were included in the study. Of these, 60 (15%) developed local recurrence at a mean median of 27 months (sd 24, range 7 to 150) and the five-year local recurrence-free survival (5yrLRFS) was 83%. For central tumours, the size of the tumour and histological response to chemotherapy were found to be significant factors for local recurrence. For limb tumours, local recurrence was affected by intralesional and marginal resections, but not by the histological response to chemotherapy. Radiotherapy in those with a marginal resection reduced the risk of local recurrence (5yrLRFS: 96% versus 81%, p = 0.044). Local recurrence significantly affects the overall survival in patients with a Ewing's sarcoma. For those with a tumour in a limb, radiotherapy reduced the risk of local recurrence, especially in those with a marginal margin of excision, but the effect in central tumours was less clear. Radiotherapy for those who have had a wide margin of resection does not reduce the risk of local recurrence, regardless of the histological response to chemotherapy. Cite this article: Bone Joint J 2018;100-B: 247-55. ©2018 The British Editorial Society of Bone & Joint Surgery.

Radioactive Seed Localization or Wire-guided Localization of Nonpalpable Invasive and In Situ Breast Cancer: A Randomized, Multicenter, Open-label Trial.

PubMed

Langhans, Linnea; Tvedskov, Tove F; Klausen, Thomas L; Jensen, Maj-Britt; Talman, Maj-Lis; Vejborg, Ilse; Benian, Cemil; Roslind, Anne; Hermansen, Jonas; Oturai, Peter S; Bentzon, Niels; Kroman, Niels

2017-07-01

To compare the rate of positive resection margins between radioactive seed localization (RSL) and wire-guided localization (WGL) after breast conserving surgery (BCS). WGL is the current standard for localization of nonpalpable breast lesions in BCS, but there are several difficulties related to the method. From January 1, 2014 to February 4, 2016, patients with nonpalpable invasive breast cancer or DCIS visible on ultrasound were enrolled in this randomized, multicenter, open-label clinical trial, and randomly assigned to RSL or WGL. The primary outcome was margin status after BCS. Secondary outcomes were duration of the surgical procedure, weight of surgical specimen, and patients' pain perception. Analyses were performed by intention-to-treat (ITT) and per protocol. Out of 444 eligible patients, 413 lesions representing 409 patients were randomized; 207 to RSL and 206 to WGL. Twenty-three did not meet inclusion criteria, chose to withdraw, or had a change in surgical management and were excluded. The remaining 390 lesions constituted the ITT population. Here, resection margins were positive in 23 cases (11.8%) in the RSL group compared with 26 cases (13.3%) in the WGL group (P = 0.65). The per-protocol analysis revealed no difference in margin status (P = 0.62). There were no significant differences in the duration of the surgical procedure (P = 0.12), weight of the surgical specimen (P = 0.54) or the patients' pain perception (P = 0.28). RSL offers a major logistic advantage, as localization can be done several days before surgery without any increase in positive resection margins compared with WGL.

Extreme hepatic resections for the treatment of advanced hepatoblastoma: Are planned close margins an acceptable approach?

PubMed

Fonseca, Adriana; Gupta, Abha; Shaikh, Furqan; Ramphal, Raveena; Ng, Vicky; McGilvray, Ian; Gerstle, J Ted

2018-02-01

Orthotopic liver transplantation (OLT) is considered the standard for children with hepatoblastoma (HB) in whom complete surgical resection is not possible. However, OLT is not always available or feasible. To describe the outcome of children with HB who were initially deemed unresectable and underwent complex hepatectomy with planned close margins, and ultimately avoided OLT. Demographic data, surgical and pathologic details, and survival information were collected from children treated for HB between January 2010 to December 2015. Among six children (median age 12 months (3-41 months)), PRETEXT classification was III (n = 2), III/IV (n = 1), and IV (n = 3). Patients received a median of six cycles (range 4-7) of platinum-based induction chemotherapy; five received doxorubicin. Experienced pediatric surgeons performed extended right and left hepatectomy in five and one patients, respectively, with assistance of an experienced liver transplant surgeon (n = 4). Microscopic margins were positive (n = 2) and negative but close (n = 4; 2-5 mm). Two patients required vascular reconstruction of the vena cava. At median follow-up of 3.3 years (1.7-4.6 years), there was no evidence of local recurrence. One patient had recurrence of pulmonary disease 3 months after surgery. Patients with advanced HB treated with complex surgical resections with positive or close negative margins had good outcomes without OLT. We suggest that planned positive or close microscopic margins in highly selected HB patients may spare the morbidity of OLT and offer an alternative for those ineligible for OLT. Our experience illustrates the importance of a multidisciplinary team specialized in the management of liver tumors. © 2017 Wiley Periodicals, Inc.

HPV-testing versus HPV-cytology co-testing to predict the outcome after conization.

PubMed

Bruhn, Laerke Valsøe; Andersen, Sisse Josephine; Hariri, Jalil

2018-06-01

The purpose of this study was to determine the feasibility of human Papillomavirus (HPV) testing alone as a prognostic tool to predict recurrent disease within a three-year follow-up period after treatment for cervical intraepithelial neoplasia (CIN)2 + . Retrospectively, 128 women with histologically verified CIN2 + who had a conization performed at Southern Jutland Hospital in Denmark between 1 January 2013 and 31 December 2013 were included. Histology, cytology and HPV test results were obtained for a three-year follow-up period. 4.7% (6/128) of the cases developed recurrent disease during follow-up. Of the cases without free margins, recurrent dysplasia was detected normal in 10.4% (5/48), whereas in the group with free margins it was 1.3% (1/80). The post-conization HPV test was negative in 67.2% (86/128) and Pap smear normal in 93.7% (120/128). Combining resection margins, cytology and HPV had sensitivity for prediction of recurrent dysplasia of 100%. Specificity was 45.8%, positive predictive value (PPV) 8.5% and negative predictive value (NPV) 100%. Using HPV test alone as a predictor of recurrent dysplasia gave a sensitivity of 83.3%, specificity 69.7%, PPV 11.9% and NPV 98.8%. Combining resection margin and HPV test had a sensitivity of 100%, specificity 45.9%, PPV 8.3% and NPV 100%. HPV test at six months control post-conization gave an NPV of 98.8% and can be used as a solitary test to identify women at risk for recurrent disease three years after treatment for precursor lesions. Using both resection margin and HPV test had a sensitivity of 100% and NPV 100%. Adding cytology did not increase the predictive value. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Standardized reporting of resection technique during nephron-sparing surgery: the surface-intermediate-base margin score.

PubMed

Minervini, Andrea; Carini, Marco; Uzzo, Robert G; Campi, Riccardo; Smaldone, Marc C; Kutikov, Alexander

2014-11-01

A standardized reporting system of nephron-sparing surgery resection techniques is lacking. The surface-intermediate-base scoring system represents a formal reporting instrument to assist in interpretation of reported data and to facilitate comparisons in the urologic literature. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Qualitative and quantitative comparison of colonic microendoscopy image features to histopathology

NASA Astrophysics Data System (ADS)

Prieto, Sandra P.; Powless, Amy J.; Lai, Keith; Laryea, Jonathan A.; Mizell, Jason S.; Muldoon, Timothy J.

2015-03-01

Colorectal cancer is the second leading cause of cancer deaths in the United States, affecting more than 130,000 Americans every year1. Determining tumor margins prior to surgical resection is essential to providing optimal treatment and reducing recurrence rates. Colorectal cancer recurrence can occur in up to 20% of cases, commonly within three years after curative treatment. Typically, when colorectal cancers are resected, a margin of normal tissue on both sides of the tumor is required. The minimum margin required for colon cancer is 5 cm and for the lower rectum 2 cm. However, usually more normal tissue is taken on both sides of the tumor because the blood supply to the entire segment is removed with the surgery and therefore the entire segment must be removed. Anastomotic recurrences may result from inadequate margins. Pathologists look at the margins to ensure that there is no residual tumor and this is usually documented in the pathology report. We have developed a portable, point-of-care fiber bundle microendoscopy imaging system for detection of abnormalities in colonic epithelial microstructure. The system comprises a laptop, a modified fiber bundle image guide with a 1mm active area diameter and custom LabVIEW interface, and is approved for imaging surgically resected colon tissue at the University of Arkansas for Medical Sciences. The microendoscopy probe provides high-resolution images of superficial epithelial histology in real-time to assist surgical guidance and to localize occult regions of dysplasia which may not be visible. Microendoscopy images of freshly resected human colonic epithelium were acquired using the microendoscopy device and subsequently mosaicked using custom post-processing software. Architectural changes in the glands were mapped to histopathology H&E slides taken from the precise location of the microendoscopy images. Qualitatively, glandular distortion and placement of image guide was used to map normal and dysplastic areas of the colonic tumor and surrounding region from microendoscopy images to H&E slides. Quantitative metrics for correlating images were also explored and were obtained by analyzing glandular diameter and spatial distribution as well as image texture.

Assessment of Surgical Learning Curves in Transoral Robotic Surgery for Squamous Cell Carcinoma of the Oropharynx

PubMed Central

Albergotti, William G.; Gooding, William E.; Kubik, Mark W.; Geltzeiler, Mathew; Kim, Seungwon; Duvvuri, Umamaheswar; Ferris, Robert L.

2017-01-01

IMPORTANCE Transoral robotic surgery (TORS) is increasingly employed as a treatment option for squamous cell carcinoma of the oropharynx (OPSCC). Measures of surgical learning curves are needed particularly as clinical trials using this technology continue to evolve. OBJECTIVE To assess learning curves for the oncologic TORS surgeon and to identify the number of cases needed to identify the learning phase. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of all patients who underwent TORS for OPSCC at the University of Pittsburgh Medical Center between March 2010 and March 2016. Cases were excluded for involvement of a subsite outside of the oropharynx, for nonmalignant abnormality or nonsquamous histology, unknown primary, no tumor in the main specimen, free flap reconstruction, and for an inability to define margin status. EXPOSURES Transoral robotic surgery for OPSCC. MAIN OUTCOMES AND MEASURES Primary learning measures defined by the authors include the initial and final margin status and time to resection of main surgical specimen. A cumulative sum learning curve was developed for each surgeon for each of the study variables. The inflection point of each surgeon’s curve was considered to be the point signaling the completion of the learning phase. RESULTS There were 382 transoral robotic procedures identified. Of 382 cases, 160 met our inclusion criteria: 68 for surgeon A, 37 for surgeon B, and 55 for surgeon C. Of the 160 included patients, 125 were men and 35 were women. The mean (SD) age of participants was 59.4 (9.5) years. Mean (SD) time to resection including robot set-up was 79 (36) minutes. The inflection points for the final margin status learning curves were 27 cases (surgeon A) and 25 cases (surgeon C). There was no inflection point for surgeon B for final margin status. Inflection points for mean time to resection were: 39 cases (surgeon A), 30 cases (surgeon B), and 27 cases (surgeon C). CONCLUSIONS AND RELEVANCE Using metrics of positive margin rate and time to resection of the main surgical specimen, the learning curve for TORS for OPSCC is surgeon-specific. Inflection points for most learning curves peak between 20 and 30 cases. PMID:28196200

Lung segment geometry study: simulation of largest possible tumours that fit into bronchopulmonary segments.

PubMed

Welter, S; Stöcker, C; Dicken, V; Kühl, H; Krass, S; Stamatis, G

2012-03-01

Segmental resection in stage I non-small cell lung cancer (NSCLC) has been well described and is considered to have similar survival rates as lobectomy but with increased rates of local tumour recurrence due to inadequate parenchymal margins. In consequence, today segmentectomy is only performed when the tumour is smaller than 2 cm. Three-dimensional reconstructions from 11 thin-slice CT scans of bronchopulmonary segments were generated, and virtual spherical tumours were placed over the segments, respecting all segmental borders. As a next step, virtual parenchymal safety margins of 2 cm and 3 cm were subtracted and the size of the remaining tumour calculated. The maximum tumour diameters with a 30-mm parenchymal safety margin ranged from 26.1 mm in right-sided segments 7 + 8 to 59.8 mm in the left apical segments 1-3. Using a three-dimensional reconstruction of lung CT scans, we demonstrated that segmentectomy or resection of segmental groups should be feasible with adequate margins, even for larger tumours in selected cases. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Towards real-time detection of tumor margins using photothermal imaging of immune-targeted gold nanoparticles

PubMed Central

Jakobsohn, Kobi; Motiei, Menachem; Sinvani, Moshe; Popovtzer, Rachela

2012-01-01

Background One of the critical problems in cancer management is local recurrence of disease. Between 20% and 30% of patients who undergo tumor resection surgery require reoperation due to incomplete excision. Currently, there are no validated methods for intraoperative tumor margin detection. In the present work, we demonstrate the potential use of gold nanoparticles (GNPs) as a novel contrast agent for photothermal molecular imaging of cancer. Methods Phantoms containing different concentrations of GNPs were irradiated with continuous-wave laser and measured with a thermal imaging camera which detected the temperature field of the irradiated phantoms. Results The results clearly demonstrate the ability to distinguish between cancerous cells specifically targeted with GNPs and normal cells. This technique, which allows highly sensitive discrimination between adjacent low GNP concentrations, will allow tumor margin detection while the temperature increases by only a few degrees Celsius (for GNPs in relevant biological concentrations). Conclusion We expect this real-time intraoperative imaging technique to assist surgeons in determining clear tumor margins and to maximize the extent of tumor resection while sparing normal background tissue. PMID:22956871

Microsurgical resection of intramedullary spinal cord hemangioblastoma.

PubMed

McCormick, Paul C

2014-09-01

Spinal cord hemangioblastomas account for about 10% of spinal cord tumors. They usually arise from the dorsolateral pia mater and are characterized by their significant vascularity. The principles and techniques of safe resection are different than those employed for the more commonly occurring intramedullary glial tumors (e.g. ependymoma, astrocytoma) and consist of circumferential detachment of the tumor margin from the surrounding normal pia. This video demonstrates the microsurgical techniques of resection of a thoracic spinal cord hemangioblastoma. The video can be found here: http://youtu.be/yT5KLi4VyAo.

Palliative photodynamic therapy for biliary tract carcinoma may improve survival and has a similar outcome to attempted curative surgery with positive resection margins

NASA Astrophysics Data System (ADS)

Pereira, Stephen P.; Matull, W. Rudiger; Dhar, Dipok K.; Ayaru, Laskshmana; Sandanayake, Neomal S.; Chapman, Michael H.

2009-06-01

There is a need for better management strategies to improve survival and quality of life in patients with biliary tract cancer (BTC). We compared treatment outcomes in 321 patients (median age 65 years, range 29-102; F:M; 1:1) with a final diagnosis of BTC (cholangiocarcinoma n=237, gallbladder cancer n=84) seen in a tertiary referral cancer centre between 1998-2007. Of 89 (28%) patients who underwent surgical intervention with curative intent, 38% had R0 resections and had the most favourable outcome, with a 3 year survival of 57%. Even though PDT patients had more advanced clinical T-stages, their survival was similar to those treated with attempted curative surgery which resulted in R1/2 resections (median survival 12 vs. 13 months, ns). In a subgroup of 36 patients with locally advanced BTC treated with PDT as part of a prospective phase II study, the median survival was 12 (range 2-51) months, compared with 5 months in matched historical controls treated with stenting alone (p < 0.0001). In this large UK series, long-term survival with BTC was only achieved in surgical patients with R0 resection margins. Palliative PDT resulted in similar survival to those with curatively intended R1/R2 resections.

Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence

PubMed Central

Lansdell, Casey; Alkayyal, Almohanad A.; Baxter, Katherine E.; Angka, Leonard; Zhang, Jiqing; Tanese de Souza, Christiano; Stephenson, Kyle B.; Parato, Kelley; Bramson, Jonathan L.; Bell, John C.; Lichty, Brian D.; Auer, Rebecca C.

2016-01-01

Anti-tumor CD8+ T cells are a key determinant for overall survival in patients following surgical resection for solid malignancies. Using a mouse model of cancer vaccination (adenovirus expressing melanoma tumor-associated antigen (TAA)—dopachrome tautomerase (AdDCT) and resection resulting in major surgical stress (abdominal nephrectomy), we demonstrate that surgical stress results in a reduction in the number of CD8+ T cell that produce cytokines (IFNγ, TNFα, Granzyme B) in response to TAA. This effect is secondary to both reduced proliferation and impaired T cell function following antigen binding. In a prophylactic model, surgical stress completely abrogates tumor protection conferred by vaccination in the immediate postoperative period. In a clinically relevant surgical resection model, vaccinated mice undergoing a positive margin resection with surgical stress had decreased survival compared to mice with positive margin resection alone. Preoperative immunotherapy with IFNα significantly extends survival in surgically stressed mice. Importantly, myeloid derived suppressor cell (MDSC) population numbers and functional impairment of TAA-specific CD8+ T cell were altered in surgically stressed mice. Our observations suggest that cancer progression may result from surgery-induced suppression of tumor-specific CD8+ T cells. Preoperative immunotherapies aimed at targeting the prometastatic effects of cancer surgery will reduce recurrence and improve survival in cancer surgery patients. PMID:27196057

Defining Hepatoblastoma Responsiveness to Induction Therapy as Measured by Tumor Volume and Serum α-fetoprotein Kinetics

PubMed Central

Lovvorn, Harold N.; Ayers, Dan; Zhao, Zhiguo; Hilmes, Melissa; Prasad, Pinki; Shinall, Myrick C.; Berch, Barry; Neblett, Wallace W.; O'Neill, James A.

2010-01-01

Purpose Hepatoblastoma is commonly unresectable at presentation, necessitating induction chemotherapy before definitive resection. To refine the paradigm for timing of resection, we questioned whether a plateau in hepatoblastoma responsiveness to neoadjuvant therapy could be detected by calculating tumor volume (TV) and serum α-fetoprotein (sAFP) kinetics. Methods To calculate TV and sAFP as measures of treatment responsiveness over time, infants having initially unresectable epithelial-type hepatoblastomas were identified at a single institution (1996-2008). Effects of therapy type, therapy duration, and lobe of liver involvement on TV, sAFP, margin status, and toxicity were analyzed. Results Of 24 infants treated for epithelial-type hepatoblastoma during this interval, 5 were resected primarily, and 15 had complete digital films for kinetics analysis. Both TV and sAFP decreased dramatically over time (p<0.0001). No statistically significant difference in mean TV or sAFP was detected after chemotherapy cycle 2. Left lobe tumors had greater presenting levels of and significantly slower decay in sAFP compared to right lobe tumors (p=0.005), although no statistically significant differences in TV existed between liver lobes. Resection margins did not change with therapy duration. Conclusions Measuring TV and sAFP kinetics accurately reflects hepatoblastoma responsiveness to induction therapy. Treatment toxicities may be reduced by earlier resection and tailoring of chemotherapeutic regimens. PMID:20105591

Extent of field change in colorectal cancers with BRAF mutation

PubMed Central

Poh, Aaron; Chang, Heidi Sian Ying; Tan, Kok Yang; Sam, Xin Xiu; Khoo, Avery; Choo, Shoa Nian; Nga, Min En; Wan, Wei Keat

2018-01-01

INTRODUCTION Sporadic colorectal cancers with BRAF mutations constitute two distinct subgroups of colorectal cancers. Recent studies have linked the presence of the BRAF mutation to a familial inheritance pattern. This was a proof-of-concept study that aimed to examine: (a) the extent of field change in sporadic colorectal cancers with BRAF mutation; and (b) the extent of resection margins required and the pattern of DNA mismatch repair protein loss in these tumours. METHODS Eight microsatellite instability-high tumours with positive BRAF mutation from an existing histopathological database were selected for BRAF mutation and mismatch repair protein analysis. RESULTS All the resection margins were negative for BRAF mutation. Three tumours had loss of MLH1 and PMS2 expressions, and five tumours had no protein loss. Six peritumoral tissues were negative and one was positive for BRAF mutation. CONCLUSION The results suggest that any early field change effect is restricted to the immediate vicinity of the tumour and is not a pan-colonic phenomenon. Current guidelines on resection margins are adequate for BRAF mutation-positive colorectal cancers. Any suggestion of a hereditary link to these tumours is likely not related to germline BRAF gene mutations. The pattern of protein loss reinforces previous findings for the two subgroups of BRAF mutation-positive colorectal cancers. PMID:28210747

Development and evaluation of a connective tissue phantom model for subsurface visualization of cancers requiring wide local excision

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Bates, Brent D.; Tselepidakis, Niki N.; DSouza, Alisha V.; Gunn, Jason R.; Ramkumar, Dipak B.; Paulsen, Keith D.; Pogue, Brian W.; Henderson, Eric R.

2017-12-01

Wide local excision (WLE) of tumors with negative margins remains a challenge because surgeons cannot directly visualize the mass. Fluorescence-guided surgery (FGS) may improve surgical accuracy; however, conventional methods with direct surface tumor visualization are not immediately applicable, and properties of tissues surrounding the cancer must be considered. We developed a phantom model for sarcoma resection with the near-infrared fluorophore IRDye 800CW and used it to iteratively define the properties of connective tissues that typically surround sarcoma tumors. We then tested the ability of a blinded surgeon to resect fluorescent tumor-simulating inclusions with ˜1-cm margins using predetermined target fluorescence intensities and a Solaris open-air fluorescence imaging system. In connective tissue-simulating phantoms, fluorescence intensity decreased with increasing blood concentration and increased with increasing intralipid concentrations. Fluorescent inclusions could be resolved at ≥1-cm depth in all inclusion concentrations and sizes tested. When inclusion depth was held constant, fluorescence intensity decreased with decreasing volume. Using targeted fluorescence intensities, a blinded surgeon was able to successfully excise inclusions with ˜1-cm margins from fat- and muscle-simulating phantoms with inclusion-to-background contrast ratios as low as 2∶1. Indirect, subsurface FGS is a promising tool for surgical resection of cancers requiring WLE.

Hilar cholangiocarcinoma: diagnosis, treatment options, and management

PubMed Central

Soares, Kevin C.; Kamel, Ihab; Cosgrove, David P.; Herman, Joseph M.

2014-01-01

Hilar cholangiocarcinoma (HC) is a rare disease with a poor prognosis which typically presents in the 6th decade of life. Of the 3,000 cases seen annually in the United States, less than one half of these tumors are resectable. A variety of risk factors have been associated with HC, most notably primary sclerosing cholangitis (PSC), biliary stone disease and parasitic liver disease. Patients typically present with abdominal pain, pruritis, weight loss, and jaundice. Computed topography (CT), magnetic resonance imaging (MRI), and ultrasound (US) are used to characterize biliary lesions. Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) assess local ductal extent of the tumor while allowing for therapeutic biliary drainage. MRCP has demonstrated similar efficacies to PTC and ERCP in identifying anatomic extension of tumors with less complications. Treatment consists of surgery, radiation, chemotherapy and photodynamic therapy. Biliary drainage of the future liver remnant should be performed to decrease bilirubin levels thereby facilitating future liver hypertrophy. Standard therapy consists of surgical margin-negative (R0) resection with extrahepatic bile duct resection, hepatectomy and en bloc lymphadenectomy. Local resection should not be undertaken. Lymph node invasion, tumor grade and negative margins are important prognostic indicators. In instances where curative resection is not possible, liver transplantation has demonstrated acceptable outcomes in highly selected patients. Despite the limited data, chemotherapy is indicated for patients with unresectable tumors and adequate functional status. Five-year survival after surgical resection of HC ranges from 10% to 40% however, recurrence can be as high as 50-70% even after R0 resection. Due to the complexity of this disease, a multi-disciplinary approach with multimodal treatment is recommended for this complex disease. PMID:24696835

Total robotic radical rectal resection with da Vinci Xi system: single docking, single phase technique.

PubMed

Tamhankar, Anup Sunil; Jatal, Sudhir; Saklani, Avanish

2016-12-01

This study aims to assess the advantages of Da Vinci Xi system in rectal cancer surgery. It also assesses the initial oncological outcomes after rectal resection with this system from a tertiary cancer center in India. Robotic rectal surgery has distinct advantages over laparoscopy. Total robotic resection is increasing following the evolution of hybrid technology. The latest Da Vinci Xi system (Intuitive Surgical, Sunnyvale, USA) is enabled with newer features to make total robotic resection possible with single docking and single phase. Thirty-six patients underwent total robotic resection in a single phase and single docking. We used newer port positions in a straight line. Median distance from the anal verge was 4.5 cm. Median robotic docking time and robotic procedure time were 9 and 280 min, respectively. Median blood loss was 100 mL. One patient needed conversion to an open approach due to advanced disease. Circumferential resection margin and longitudinal resection margins were uninvolved in all other patients. Median lymph node yield was 10. Median post-operative stay was 7 days. There were no intra-operative adverse events. The latest Da Vinci Xi system has made total robotic rectal surgery feasible in single docking and single phase. With the new system, four arm total robotic rectal surgery may replace the hybrid technique of laparoscopic and robotic surgery for rectal malignancies. The learning curve for the new system appears to be shorter than anticipated. Early perioperative and oncological outcomes of total robotic rectal surgery with the new system are promising. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Laser-supported diaphanoscopy: an innovative technique for locating gastric stromal tumors in gastroscopic-laparoscopic rendezvous: a case series.

PubMed

Patrzyk, M; Schreiber, A; Heidecke, C D; Glitsch, A

2009-12-01

Development of an innovative method of endoscopic laser-supported diaphanoscopy, for precise demonstration of the location of gastrointestinal stromal tumors (GISTs) at laparoscopy is described. The equipment consists of a light transmission cable with an anchoring system for the gastric mucosa, a connecting system for the light source, and the laser light source itself. During surgery, transillumination by laser is used to show the shape of the tumor. The resection margins are then marked by electric coagulation. Ten patients have been successfully treated using this technique in laparoscopic-endoscopic rendezvous procedures. Average time of surgery was 123 minutes. The time for marking the shape of the tumor averaged 16 minutes. Depending on tumor location and size, 4-7 marks were used, and resection margins were 4-15 mm. This new and effective technique facilitates precise locating of gastric GISTs leading to exact and tissue-sparing transmural laparoscopic resections. Georg Thieme Verlag KG Stuttgart New York.

Fluorescence detection of malignant liver tumors using 5-aminolevulinic acid-mediated photodynamic diagnosis: principles, technique, and clinical experience.

PubMed

Inoue, Yoshihiro; Tanaka, Ryo; Komeda, Koji; Hirokawa, Fumitoshi; Hayashi, Michihiro; Uchiyama, Kazuhisa

2014-07-01

Photoactive drugs selectively accumulate in malignant tissue specimens and cause drug-induced fluorescence. Photodynamic diagnosis (PDD) and fluorescence can distinguish normal from malignant tissue. From May 2012 to September 2013, a total of 70 patients underwent hepatic resections using 5-ALA-mediated PDD for liver tumors at our hospital. 5-ALA fluorescence was detected in all hepatocellular carcinoma cases with serosa invasion. In liver metastasis from colorectal cancer cases with serosa invasion, 18 patients (85.7 %) were detected, and three patients (14.2 %) whose tumors showed complete response to neoadjuvant chemotherapy showed no fluorescence. Both superficial and deep malignant liver tumors were detected with 92.5 % sensitivity. Using 5-ALA-mediated PDD, tumors remaining at the cut surface and postoperative bile leakage were less frequent than in our previous hepatic resections using conventional white-light observation. Moreover, all malignant liver tumors were completely removed with a clear microscopic margin using 5-ALA, with a significant difference in resection margin width between 5-ALA-mediated PDD (6.7 ± 6.9 mm) and white-light observation (9.2 ± 7.0 mm; p = 0.0083). With the detection of malignant liver tumors, residual tumor and bile leakage at the cut surface of the remnant liver were improved by PDD with 5-ALA. This procedure may provide greater sensitivity than the conventional procedure. Furthermore, 5-ALA-mediated PDD can ensure histological clearance regardless of the resection margin and preserve as much liver parenchyma as possible in patients with impaired liver function.

Fluorophore-conjugated antibodies for imaging and resection of GI tumors

NASA Astrophysics Data System (ADS)

Bouvet, Michael; Hoffman, Robert M.

2016-03-01

Negative surgical margins are critical to prevent recurrence in cancer surgery. This is because with current technology in many cases negative margins are impossible due the inability of the surgeon to detect the margin. Our laboratory has developed fluorophore-labeled monoclonal antibodies to aid in cancer visualization in orthotopic nude mouse models of human gastrointestinal (GI) cancer in order to achieve negative margins in fluorescence-guided surgery (FGS). The technologies described herein have the potential to change the paradigm of surgical oncology to engender significantly improved outcomes.

Surgery for Locally Recurrent Rectal Cancer: Tips, Tricks, and Pitfalls.

PubMed

Warrier, Satish K; Heriot, Alexander G; Lynch, Andrew Craig

2016-06-01

Rectal cancer can recur locally in up to 10% of the patients who undergo definitive resection for their primary cancer. Surgical salvage is considered appropriate in the curative setting as well as select cases with palliative intent. Disease-free survival following salvage resection is dependent upon achieving an R0 resection margin. A clear understanding of applied surgical anatomy, appropriate preoperative planning, and a multidisciplinary approach to aggressive soft tissue, bony, and vascular resection with appropriate reconstruction is necessary. Technical tips, tricks, and pitfalls that may assist in managing these cancers are discussed and the roles of additional boost radiation and intraoperative radiation therapy in the management of such cancers are also discussed.

Near-infrared intraoperative imaging during resection of an anterior mediastinal soft tissue sarcoma.

PubMed

Predina, Jarrod D; Newton, Andrew D; Desphande, Charuhas; Singhal, Sunil

2018-01-01

Sarcomas are rare malignancies that are generally treated with multimodal therapy protocols incorporating complete local resection, chemotherapy and radiation. Unfortunately, even with this aggressive approach, local recurrences are common. Near-infrared intraoperative imaging is a novel technology that provides real-time visual feedback that can improve identification of disease during resection. The presented study describes utilization of a near-infrared agent (indocyanine green) during resection of an anterior mediastinal sarcoma. Real-time fluorescent feedback provided visual information that helped the surgeon during tumor localization, margin assessment and dissection from mediastinal structures. This rapidly evolving technology may prove useful in patients with primary sarcomas arising from other locations or with other mediastinal neoplasms.

Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM(197) conjugate vaccine co-localizes with MHC II on the antigen processing cell surface.

PubMed

Lai, Zengzu; Schreiber, John R

2009-05-21

Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.

Construction and Development of CRM Technology and Industry Chain in China

NASA Astrophysics Data System (ADS)

Liu, Chunnian; Wang, Yonglong; Pan, Qin

CRM is any application or initiative designed to help an organization optimize interactions with customers, suppliers, or prospects via one or more touch points. CRM has been interpreted and used in different ways by researchers in the various disciplines and researchers have identified a variety of technologies related to CRM. This paper highlights the implementation from the technology level and contributes to some successful factors in CRM application. The development of CRM is not fully developed in China. There are many critical factors that determine the CRM market development. Construction and development of CRM industry chain in China is a valuable research field and the paper provided some suggestions and analyses on it. In future, it requires our joint efforts of many aspects from every walk of life to make sure that CRM industry chain can improve and maturate gradually.

Novel Totally Laparoscopic Endolumenal Rectal Resection With Transanal Natural Orifice Specimen Extraction (NOSE) Without Rectal Stump Opening: A Modification of Our Recently Published Clean Surgical Technique in a Porcine Model.

PubMed

Kvasha, Anton; Hadary, Amram; Biswas, Seema; Szvalb, Sergio; Willenz, Udi; Waksman, Igor

2015-06-01

Our group has recently described a novel technique for clean endolumenal bowel resection, in which abdominal and transanal approaches were used. In the current study, 2 modifications of this procedure were tested for feasibility in a porcine model. A laparoscopic approach to the peritoneal cavity was employed in rectal mobilization; this was followed by a transanal rectorectal intussusception and pull-through (IPT). IPT was established in a stepwise fashion. First, the proximal margin of resection was attached to the shaft of the anvil of an end-to-end circular stapler with a ligature around the rectum. Second, this complex was pulled transanally to produce IPT. Once IPT was established, a second ligature was placed around the rectum approximating the proximal and distal resection margins. This was followed by a purse string suture through 2 bowel walls, encircling the shaft of the anvil just proximal to the ligatures. The specimen was resected and extracted by making a full-thickness incision through the 2 bowel walls distal to the previously placed purse string suture and ligatures. The anastomosis was achieved by applying the stapler. The technique was found to be feasible. Peritoneal samples, collected after transanal specimen extraction, did not demonstrate bacterial growth. Although, this is a novel and evolving procedure, its minimally invasive nature, as well as aseptic bowel manipulation during endolumenal rectal resection, has the potential to limit the complications associated with abdominal wall incision and surgical site infection. © The Author(s) 2014.

A multiplanar complex resection of a low-grade chondrosarcoma of the distal femur guided by K-wires previously inserted under CT-guide: a case report

PubMed Central

2014-01-01

Background In muscular skeletal oncology aiming to achieve wide surgical margin is one of the main factors influencing patient prognosis. In cases where lesions are either meta or epiphyseal, surgery most often compromises joint integrity and stability because muscles, tendons and ligaments are involved in wide resection. When lesions are well circumscribed they can be completely resected by performing multi-planar osteotomies guided by computer-assisted navigation. We describe a case of low-grade chondrosarcoma of the distal femur where a simple but effective technique was useful to perform complex multiplanar osteotomies. No similar techniques are reported in the literature. Case presentation A 57 year-old Caucasian female was referred to our department for the presence of a distal femur chondrosarcoma. A resection with the presenting technique was scheduled. The first step consists of inserting several K-wires under CT-scan control to delimitate the tumor; the second step consists of tumor removal: in operative theatre, following surgical access, k-wires are used as guide positioning; scalpels are externally placed to k-wires to perform a safe osteotomy. Conclusions Computed assisted resections can be considered the most advantageous method to reach the best surgical outcome; unfortunately navigation systems are only available in specialized centres. The present technique allows for a multiplanar complex resection when navigation systems are not available. This technique can be applied in low-grade tumours where a minimal wide margin can be considered sufficient. PMID:25123066

En bloc spondylectomy in malignant tumors of the spine

PubMed Central

Lerner, Thomas; Halm, Henry; Buerger, Horst; Gosheger, Georg; Winkelmann, Winfried

2008-01-01

En bloc spondylectomy is a technique that enables wide or marginal resection of malignant lesions of the spine. Both all posterior techniques as well as combined approaches are reported. Aim of the present study was to analyse the results of 21 patients with malignant lesions of the spine, all treated with en bloc excision in a combined posteroanterior (n = 19) or all posterior approach (n = 2). Twenty-one consecutive patients, operated between 1997 and 2005, were included into this retrospective study. Thirteen patients had primary malignant lesions, eight patients had solitary metastases, all located in the thoracolumbar spine. There were 16 single level, three two-level, one three-level and one four-level spondylectomy. The patients were followed clinically and radiographically (including CT studies) with an average follow-up of 4 years. Out of 11 patients with primary Ewing or osteosarcoma seven patients are alive without any evidence of disease. One patient died after 5 years from other causes and three are alive with evidence of disease. Latter had either a poor histologic response to the preoperative chemotherapy (n = 2) or an intralesional resection (n = 1). All three patients with solitary spinal metastases of Ewing or osteosarcoma died of the disease. Five patients with solitary metastases of mainly hypernephroma are alive. In total, six resections were intralesional, mainly due to large intraspinal tumor masses, with two patients having had previous surgery. In the remaining cases, wide (n = 10) or marginal (n = 5) resection was accomplished. There were one pseudarthrosis requiring extension of the fusion and two cases with local recurrences and repeated excisional surgery. At follow-up CT studies, all cages were fused. Health related quality of life analysis (SF-36) revealed only slightly decreased physical component and normal mental component scores compared to normals in those patients with no evidence of disease. En bloc spondylectomy enables wide or marginal resection of malignant lesions of the spine in most cases with acceptable morbidity. Intralesional resection, poor histologic response, and solitary spinal metastases of Ewing and osteosarcoma are associated with a poor prognosis. PMID:18214553

Bioavailability of a Lipidic Formulation of Curcumin in Healthy Human Volunteers

PubMed Central

Pawar, Yogesh B.; Munjal, Bhushan; Arora, Saurabh; Karwa, Manoj; Kohli, Gunjan; Paliwal, Jyoti K.; Bansal, Arvind K.

2012-01-01

Numerous publications have reported the significant pharmacodynamic activity of Curcumin (CRM) despite low or undetectable levels in plasma. The objective of the present study was to perform a detailed pharmacokinetic evaluation of CRM after the oral administration of a highly bioavailable lipidic formulation of CRM (CRM-LF) in human subjects. Cmax, Tmax and AUC0–∞ were found to be 183.35 ± 37.54 ng/mL, 0.60 ± 0.05 h and 321.12 ± 25.55 ng/mL respectively, at a dose of 750 mg. The plasma profile clearly showed three distinct phases, viz., absorption, distribution and elimination. A close evaluation of the primary pharmacokinetic parameters provided valuable insight into the behavior of the CRM after absorption by CRM-LF. CRM-LF showed a lag time (Tlag) of 0.18 h (around 12 min). Pharmacokinetic modeling revealed that CRM-LF followed a two-compartment model with first order absorption, lag time and first order elimination. A high absorption rate constant (K01, 4.51/h) signifies that CRM-LF ensured rapid absorption of the CRM into the central compartment. This was followed by the distribution of CRM from the central to peripheral compartment (K12, 2.69/h). The rate of CRM transfer from the peripheral to central compartment (K21, 0.15/h) was slow. This encourages higher tissue levels of CRM as compared with plasma levels. The study provides an explanation of the therapeutic efficacy of CRM, despite very low/undetectable levels in the plasma. PMID:24300368

Technical aspects of virtual liver resection planning.

PubMed

Glombitza, G; Lamadé, W; Demiris, A M; Göpfert, M R; Mayer, A; Bahner, M L; Meinzer, H P; Richter, G; Lehnert, T; Herfarth, C

1998-01-01

Operability of a liver tumor is depending on its three dimensional relation to the intrahepatic vascular trees which define autonomously functioning liver (sub-)segments. Precise operation planning is complicated by anatomic variability, distortion of the vascular trees by the tumor or preceding liver resections. Because of the missing possibility to track the deformation of the liver during the operation an integration of the resection planning system into an intra-operative navigation system is not feasible. So the main task of an operation planning system in this domain is a quantifiable patient selection by exact prediction of post-operative liver function and a quantifiable resection proposal. The system quantifies the organ structures and resection volumes by means of absolute and relative values. It defines resection planes depending on security margins and the vascular trees and presents the data in visualized form as a 3D movie. The new 3D operation planning system offers quantifiable liver resection proposals based on individualized liver anatomy. The results are visualized in digital movies as well as in quantitative reports.

Preoperative selection of patients with colorectal cancer liver metastasis for hepatic resection

PubMed Central

Mattar, Rafif E; Al-alem, Faisal; Simoneau, Eve; Hassanain, Mazen

2016-01-01

Surgical resection of colorectal liver metastases (CRLM) has a well-documented improvement in survival. To benefit from this intervention, proper selection of patients who would be adequate surgical candidates becomes vital. A combination of imaging techniques may be utilized in the detection of the lesions. The criteria for resection are continuously evolving; currently, the requirements that need be met to undergo resection of CRLM are: the anticipation of attaining a negative margin (R0 resection), whilst maintaining an adequate functioning future liver remnant. The timing of hepatectomy in regards to resection of the primary remains controversial; before, after, or simultaneously. This depends mainly on the tumor burden and symptoms from the primary tumor. The role of chemotherapy differs according to the resectability of the liver lesion(s); no evidence of improved survival was shown in patients with resectable disease who received preoperative chemotherapy. Presence of extrahepatic disease in itself is no longer considered a reason to preclude patients from resection of their CRLM, providing limited extra-hepatic disease, although this currently is an area of active investigations. In conclusion, we review the indications, the adequate selection of patients and perioperative factors to be considered for resection of colorectal liver metastasis. PMID:26811608

CRM System Implementation in a Multinational Enterprise

NASA Astrophysics Data System (ADS)

Mishra, Alok; Mishra, Deepti

The concept of customer relationship management (CRM) resonates with managers in today's competitive economy. As more and more organizations realize the significance of becoming customer-centric in today's competitive era, they embrace CRM as a core business strategy. CRM an integration of information technology and relationship marketing provides the infrastructure that facilitates long-term relationship building with customers at an enterprise-wide level. Successful CRM implementation is a complex, expensive and rarely technical projects. This paper presents the successful implementation of CRM in a multinational organization. This study will facilitate in understanding transition, constraints and implementation of CRM in multinational enterprises.

Impact of crisis resource management simulation-based training for interprofessional and interdisciplinary teams: A systematic review.

PubMed

Fung, Lillia; Boet, Sylvain; Bould, M Dylan; Qosa, Haytham; Perrier, Laure; Tricco, Andrea; Tavares, Walter; Reeves, Scott

2015-01-01

Crisis resource management (CRM) abilities are important for different healthcare providers to effectively manage critical clinical events. This study aims to review the effectiveness of simulation-based CRM training for interprofessional and interdisciplinary teams compared to other instructional methods (e.g., didactics). Interprofessional teams are composed of several professions (e.g., nurse, physician, midwife) while interdisciplinary teams are composed of several disciplines from the same profession (e.g., cardiologist, anaesthesiologist, orthopaedist). Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ERIC were searched using terms related to CRM, crisis management, crew resource management, teamwork, and simulation. Trials comparing simulation-based CRM team training versus any other methods of education were included. The educational interventions involved interprofessional or interdisciplinary healthcare teams. The initial search identified 7456 publications; 12 studies were included. Simulation-based CRM team training was associated with significant improvements in CRM skill acquisition in all but two studies when compared to didactic case-based CRM training or simulation without CRM training. Of the 12 included studies, one showed significant improvements in team behaviours in the workplace, while two studies demonstrated sustained reductions in adverse patient outcomes after a single simulation-based CRM team intervention. In conclusion, CRM simulation-based training for interprofessional and interdisciplinary teams show promise in teaching CRM in the simulator when compared to didactic case-based CRM education or simulation without CRM teaching. More research, however, is required to demonstrate transfer of learning to workplaces and potential impact on patient outcomes.

Surgical technique and clinical results for scapular allograft reconstruction following resection of scapular tumors.

PubMed

Zhang, Kaiwei; Duan, Hong; Xiang, Zhou; Tu, Chongqi

2009-04-01

Progress in developing effective surgical techniques, such as scapular allograft reconstruction, enhance shoulder stability and extremity function, in patients following scapular tumor resection. Case details from seven patients who underwent scapular allograft reconstruction following scapular tumor resection were reviewed. A wide marginal resection (partial scapulectomy) was performed in all patients and all affected soft tissues were resected to achieve a clean surgical margin. The glenoid-resected and glenoid-saved reconstructions were performed in three and four patients, respectively. The residual host scapula were fixed to the size-matched scapular allografts with plates and screws. The rotator cuff was affected frequently and was mostly resected. The deltoid and articular capsule were infrequently involved, but reconstructed preferentially. The remaining muscles were reattached to the allografts. The median follow-up was 26 months (range, 14-50 months). The average function scores were 24 points (80%) according to the International Society of Limb Salvage criteria. The range of active shoulder abduction and forward flexion motion were 40 degrees -110 degrees and 30 degrees -90 degrees, respectively. There was no difference between the glenoid-saved and glenoid-resected reconstructions in the total scores (mean, 24.5 points/81% versus 24 points/79%), but the glenoid-saved procedure was superior to the later in terms of abduction/flexion motion (mean, 72 degrees /61 degrees versus 55 degrees /43 degrees). During the study follow-up period, one patient died following a relapse, one patient lived despite of local recurrence, and five patients survived with no evidence of recurrence of the original cancer. Post-surgical complications such as shoulder dislocations, non-unions, and articular degeneration were not noted during this study period. Scapular allograft reconstruction had a satisfactory functional, cosmetic, and oncological outcome in this case series. Preservation and reconstruction of the articular capsule and deltoid are proposed to be a prerequisite for using scapular allografts and rotator cuff reconstruction is recommended, although technically challenging to perform.

Surgical technique and clinical results for scapular allograft reconstruction following resection of scapular tumors

PubMed Central

Zhang, Kaiwei; Duan, Hong; Xiang, Zhou; Tu, Chongqi

2009-01-01

Background Progress in developing effective surgical techniques, such as scapular allograft reconstruction, enhance shoulder stability and extremity function, in patients following scapular tumor resection. Methods Case details from seven patients who underwent scapular allograft reconstruction following scapular tumor resection were reviewed. A wide marginal resection (partial scapulectomy) was performed in all patients and all affected soft tissues were resected to achieve a clean surgical margin. The glenoid-resected and glenoid-saved reconstructions were performed in three and four patients, respectively. The residual host scapula were fixed to the size-matched scapular allografts with plates and screws. The rotator cuff was affected frequently and was mostly resected. The deltoid and articular capsule were infrequently involved, but reconstructed preferentially. The remaining muscles were reattached to the allografts. Results The median follow-up was 26 months (range, 14–50 months). The average function scores were 24 points (80%) according to the International Society of Limb Salvage criteria. The range of active shoulder abduction and forward flexion motion were 40°–110° and 30°–90°, respectively. There was no difference between the glenoid-saved and glenoid-resected reconstructions in the total scores (mean, 24.5 points/81% versus 24 points/79%), but the glenoid-saved procedure was superior to the later in terms of abduction/flexion motion (mean, 72°/61° versus 55°/43°). During the study follow-up period, one patient died following a relapse, one patient lived despite of local recurrence, and five patients survived with no evidence of recurrence of the original cancer. Post-surgical complications such as shoulder dislocations, non-unions, and articular degeneration were not noted during this study period. Conclusion Scapular allograft reconstruction had a satisfactory functional, cosmetic, and oncological outcome in this case series. Preservation and reconstruction of the articular capsule and deltoid are proposed to be a prerequisite for using scapular allografts and rotator cuff reconstruction is recommended, although technically challenging to perform. PMID:19338652

The effects of implementing synoptic pathology reporting in cancer diagnosis: a systematic review.

PubMed

Sluijter, Caro E; van Lonkhuijzen, Luc R C W; van Slooten, Henk-Jan; Nagtegaal, Iris D; Overbeek, Lucy I H

2016-06-01

Pathology reporting is evolving from a traditional narrative report to a more structured synoptic report. Narrative reporting can cause misinterpretation due to lack of information and structure. In this systematic review, we evaluate the impact of synoptic reporting on completeness of pathology reports and quality of pathology evaluation for solid tumours. Pubmed, Embase and Cochrane databases were systematically searched to identify studies describing the effect of synoptic reporting implementation on completeness of reporting and quality of pathology evaluation of solid malignant tumours. Thirty-three studies met the inclusion criteria. All studies, except one, reported an increased overall completeness of pathology reports after introduction of synoptic reporting (SR). Most frequently studied cancers were breast (n = 9) and colorectal cancer (n = 16). For breast cancer, narrative reports adequately described 'tumour type' and 'nodal status'. Synoptic reporting resulted in improved description of 'resection margins', 'DCIS size', 'location' and 'presence of calcifications'. For colorectal cancer, narrative reports adequately reported 'tumour type', 'invasion depth', 'lymph node counts' and 'nodal status'. Synoptic reporting resulted in increased reporting of 'circumferential margin', 'resection margin', 'perineural invasion' and 'lymphovascular invasion'. In addition, increased numbers of reported lymph nodes were found in synoptic reports. Narrative reports of other cancer types described the traditional parameters adequately, whereas for 'resection margins' and '(lympho)vascular/perineural invasion', implementation of synoptic reporting was necessary. Synoptic reporting results in improved reporting of clinical relevant data. Demonstration of clinical impact of this improved method of pathology reporting is required for successful introduction and implementation in daily pathology practice.

A non-canonical mechanism for Crm1-export cargo complex assembly.

PubMed

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Faza, Marius Boulos; Panse, Vikram Govind

2015-04-21

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export.

Aggressive Surgical Resection of Pulmonary Artery Intimal Sarcoma.

PubMed

Yamamoto, Yoko; Shintani, Yasushi; Funaki, Soichiro; Taira, Masaki; Ueno, Takayoshi; Kawamura, Tomohiro; Kanzaki, Ryu; Minami, Masato; Sawa, Yoshiki; Okumura, Meinoshin

2018-05-03

Intimal sarcoma of the pulmonary artery is a rare and highly malignant neoplasm. We herein report a case of a 30-year-old woman with an extensive right pulmonary artery tumor who underwent an emergent operation. The tumor was aggressively resected with right pneumonectomy and reconstruction of the right ventricle outflow tract and left pulmonary artery. Although the resected margin at the left pulmonary artery was positive, as confirmed by Mouse double minute type 2 homolog staining, she is doing well and remains free of relapse at 16 months after the operation. Copyright © 2018. Published by Elsevier Inc.

Culture in the Cockpit-CRM in a Multicultural World

NASA Technical Reports Server (NTRS)

Engle, Michael

2000-01-01

Crew Resource Management (CRM) is fundamentally a method for enhancing personal interactions among crewmembers so that safety and efficiency are increased, and at its core involves issues of culture and social interaction. Since CRM is increasingly being adopted by foreign carriers, it is important to evaluate standard CRM techniques from a cultural standpoint, especially if some of these techniques may be enhanced by adapting them to particular cultures. The purpose of this paper is to propose a model for an ideal CRM culture, and to suggest ways that CRM may be adapted to suit particular cultures. The research method was a simple literature search to gather data on CRM techniques and multicultural crews. The results indicate that CRM can be tailored to specific cultures for maximum effectiveness.

Role of hilar resection in the treatment of hilar cholangiocarcinoma.

PubMed

Otani, Kazuhiro; Chijiiwa, Kazuo; Kai, Masahiro; Ohuchida, Jiro; Nagano, Motoaki; Kondo, Kazuhiro

2012-05-01

The aim of this study was to clarify the role of bile duct resection without hepatectomy (hilar resection) in hilar cholangiocarcinoma. We retrospectively compared surgical results for hilar cholangiocarcinoma between 8 patients treated with hilar resection and 21 patients treated with hepatectomy. All hilar resections were performed for Bismuth type I or II tumors with T2 or less lesions, whereas hepatectomy was done for type III or IV tumors excluding one type II tumor. R0 resection was equally achieved in both groups (62.5% in hilar resection group and 76.2% in hepatectomy group, p=0.469) and overall 5-year survival rates were comparable (21.9% vs. 23.6%, p=0.874). With respect to gross tumor appearance, R0 resection was achieved in all patients with papillary tumor in both groups with the excellent 5-year survivals (100% vs. 100%). In patients with nodular and flat tumors, R0 resection was achieved less frequently in the hilar resection vs. hepatectomy group (50% vs. 77.8%) mainly due to failure to clear the proximal ductal margin, resulting in poorer 5-year survival (0% vs. 18.7%). Hilar resection may be indicated for papillary T1 or 2 tumors in Bismuth type I or II cholangiocarcinoma.

14 CFR 121.406 - Credit for previous CRM/DRM training.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Credit for previous CRM/DRM training. 121... previous CRM/DRM training. (a) For flightcrew members, the Administrator may credit CRM training received before March 19, 1998 toward all or part of the initial ground CRM training required by § 121.419. (b...

14 CFR 121.406 - Credit for previous CRM/DRM training.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Credit for previous CRM/DRM training. 121... previous CRM/DRM training. (a) For flightcrew members, the Administrator may credit CRM training received before March 19, 1998 toward all or part of the initial ground CRM training required by § 121.419. (b...

Increasing Intelligence, Surveillance, and Reconnaissance (ISR) Operational Agility through Mission Command

DTIC Science & Technology

2016-06-10

Counterinsurgency COM Collections Operations Management CONOP Concept of Operations CRM Collections Requirements Management DOD Department of...collection requirements management ( CRM ) and collection operations management (COM). CRM is the authoritative development and control of collection...management ( CRM ) and collections operations management (COM) (see figure 6). In general, CRM advocates and prioritizes customer requirements while

A novel surgical marking system for small peripheral lung nodules based on radio frequency identification technology: Feasibility study in a canine model.

PubMed

Kojima, Fumitsugu; Sato, Toshihiko; Takahata, Hiromi; Okada, Minoru; Sugiura, Tadao; Oshiro, Osamu; Date, Hiroshi; Nakamura, Tatsuo

2014-04-01

We investigated the feasibility and accuracy of a novel surgical marking system based on radiofrequency identification (RFID) technology for the localization of small peripheral lung nodules (SPLNs) in a canine model. The system consists of 4 components: (1) micro RFID tags (13.56 MHz, 1.0 × 1.0 × 0.8 mm), (2) a tag delivery system with a bronchoscope, (3) a wand-shaped locating probe (10-mm diameter), and (4) a signal processing unit with audio interface. Before the operation, pseudolesions mimicking SPLNs were prepared in 7 dogs by injecting colored collagen. By use of a computed tomographic (CT) guide, an RFID tag was placed via a bronchoscope close to each target lesion. This was then followed by scanning with the locating probe, and wedge resection was performed when possible. Operators can locate the tag by following the sound emitted by the system, which exhibits tone changes according to the tag-probe distance. The primary outcome measure was the rate of wedge resection with good margins. A total of 10 pseudolesions imitating SPLNs were selected as targets. During thoracoscopic procedures, 9 of 10 tags were detected by the system within a median of 27 seconds. Wedge resections were performed for these 9 lesions with a median margin of 11 mm. The single failure was caused by tag dislocation to the central airway. Successful localization and wedge resection of pseudolesions with appropriate margins were accomplished in an experimental setting. Our RFID marking system has future applications for accurately locating SPLNs in a clinical setting. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

The Unresolved Case of Sacral Chordoma: From Misdiagnosis to Challenging Surgery and Medical Therapy Resistance

PubMed Central

Garofalo, Fabio; Christoforidis, Dimitrios; di Summa, Pietro G.; Gay, Béatrice; Cherix, Stéphane; Raffoul, Wassim; Matter, Maurice

2014-01-01

Purpose A sacral chordoma is a rare, slow-growing, primary bone tumor, arising from embryonic notochordal remnants. Radical surgery is the only hope for cure. The aim of our present study is to analyse our experience with the challenging treatment of this rare tumor, to review current treatment modalities and to assess the outcome based on R status. Methods Eight patients were treated in our institution between 2001 and 2011. All patients were discussed by a multidisciplinary tumor board, and an en bloc surgical resection by posterior perineal access only or by combined anterior/posterior accesses was planned based on tumor extension. Results Seven patients underwent radical surgery, and one was treated by using local cryotherapy alone due to low performance status. Three misdiagnosed patients had primary surgery at another hospital with R1 margins. Reresection margins in our institution were R1 in two and R0 in one, and all three recurred. Four patients were primarily operated on at our institution and had en bloc surgery with R0 resection margins. One had local recurrence after 18 months. The overall morbidity rate was 86% (6/7 patients) and was mostly related to the perineal wound. Overall, 3 out of 7 resected patients were disease-free at a median follow-up of 2.9 years (range, 1.6-8.0 years). Conclusion Our experience confirms the importance of early correct diagnosis and of an R0 resection for a sacral chordoma invading pelvic structures. It is a rare disease that requires a challenging multidisciplinary treatment, which should ideally be performed in a tertiary referral center. PMID:24999463

The impact of a dedicated multidisciplinary team on the management of early rectal cancer.

PubMed

Vaughan-Shaw, P G; Wheeler, J M D; Borley, N R

2015-08-01

Local excision of early rectal cancer (ERCa) offers comparable survival and reduced operative morbidity compared with radical surgery, yet it risks an adverse oncological outcome if performed in the wrong setting. This retrospective review considers the impact of the introduction of a specialist early rectal cancer multidisciplinary team (ERCa MDT) on the investigation and management of ERCa. A retrospective comparative cohort study was undertaken. Patients with a final diagnosis of pT1 rectal cancer at our unit were identified for two 12-month periods before and after the introduction of the specialist ERCa MDT. Data on investigations and therapeutic interventions were compared. Nineteen patients from 2006 and 24 from 2011 were included. In 2006, 12 patients underwent MRI and four transrectal ultrasound (TRUS) examination, while in 2011, 18 and 20, respectively, received MRI and TRUS. In 2006 four patients underwent incidental ERCa polypectomy, with all having a positive resection margin leading to anterior resection. In 2011 only one case with a positive margin following extended endoscopic mucosal resection was identified. Definitive local excision without subsequent resection occurred in two patients in 2006 and in 16 in 2011. The study demonstrates an improvement in preoperative ERCa staging, a reduction in margin positivity and an increase in the use of local excision following the implementation of a specialist ERCa MDT. The increased detection of rectal neoplasms through screening and surveillance programmes requires further investigation and management. A specialist ERCa MDT will improve management and should be available to all practitioners involved with patients with ERCa. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

[Surgical treatment and prognosis of Borrmann type IIII( gastric cancer involving the whole stomach].

PubMed

Dong, Ruizeng; Zhang, Zewei; Zhou, Yiming; Hua, Yonghong; Guo, Jianmin

2018-02-25

To explore the surgical treatment and prognosis of Borrmann type IIII( gastric cancer involving the whole stomach. Clinicopathological characteristics and survival data of 223 patients with Borrmann type IIII( gastric cancer involving the whole stomach (defined as the tumor infiltrating 3 regions of the stomach) receiving surgical treatment at the Department of Abdominal Surgery of Zhejiang Cancer Hospital between January 2002 and December 2015 were analyzed retrospectively. The survival time of patients with different clinicopathological features and different treatment methods was compared. Cox regression was used to analyze the independent prognostic factors. Two hundred and twenty-three patients with Borrmann type IIII( gastric cancer involving the whole stomach accounted for 24.0% (223/930) of all Borrmann type IIII( gastric cancer cases undergoing surgical resection at the same period. There were 147 males and 76 females with an average age of 57.8 years. All the patients underwent total gastrectomy. Of these patients, radical resection was performed in 149 cases(66.8%) and palliative resection in 74 cases (33.2%). Combined organ resection was performed in 43 patients (19.3%), including 25 splenectomies, 6 pancreatic body and tail plus spleen and transverse colon resections, 2 transverse colon plus spleen resections, 2 right colon resections, 2 transverse colon resections, 2 ovariectomies, 1 partial jejunal resection, 1 pancreatoduodenectomy, 1 pancreatic tail plus transverse colon resection, and 1 partial pancreatectomy. Postoperative complications occurred in 28 patients(12.6%), including 10 patients with combined organ resection. Esophagojejunal fistula was the most frequent complication, accounting for 39.3%(11/28). Perioperative mortality occurred in 3 patients (1.3%). Thirty-nine patients underwent preoperative adjuvant chemotherapy (clinical stage: cT4aN0M0 in 1 patient, cT4bN1-2M0 in 12 patients, cT4aN1-2M0 in 20 patients, and cT4aN3M0 in 6 patients). Among these 39 patients, post-chemotherapeutic degenerative response was detected in 25 postoperative pathological specimens (64.1%), radical resection was performed in 21 patients (53.8%), distant metastasis was observed in 7 patients (17.9%) and peritoneal metastasis was found in 17 patients (43.6%) during operation. The average maximal tumor diameter was 13.2 cm (range from 6 to 22). Histological types included 23 moderate-poorly differentiated adenocarcinomas (10.3%), 146 poorly differentiated adenocarcinomas (65.5%), 41 signet ring cell carcinomas (18.4%), 11 mucinous adenocarcinomas(4.9%), 1 squamous cell carcinoma (0.4%) and 1 undifferentiated carcinoma (0.4%). Tumor-infiltrating duodenum was found in 57 patients (25.6%) and tumor-infiltrating esophagus in 132 patients (59.2%). The positive margin was found in 66 patients (29.6%): upper margin in 35 patients (15.7%), lower margin in 22 patients (9.9%), and both margins in 9 patients(4.0%). Immunohistochemical positive HER2(3+) was detected in 4 patients (1.8%). Tumor infiltrating into serosa(T4a) was found in 197 patients (88.3%) and infiltrating into adjacent organ (T4b) in 26 patients(11.7%). One hundred and forty-three cases (64.1%) had lymphatic or venous invasion, 187 (83.9%) had neural invasion, and 35 (15.7%) had cancer nodules. Of 149 patients undergoing radical resection, 5 patients were stage II(b, 9 patients were III(a, 20 patients were III(b and 115 patients were III(c. Of 145 patients(65.0%) undergoing postoperative chemotherapy, the average cycles of chemotherapy was 3.6 (median 3 cycles) and only 69 patients (47.6%) completed 4 cycles or more. Patients were followed up for 1-102 months (average 17.3 months). The median overall survival time was 13.8 months and the 1-, 3-, and 5-year survival rate was 57.9%, 14.1% and 6.8% respectively. The median survival time of the 149 cases with radical resection was 16.7 months and the 1-, 3- and 5-year survival rate was 67.5%, 16.5% and 8.4% respectively; the median survival time of the 74 cases with palliative resection was 10.3 months and the 1-, 3- and 5-year survival rate was 42.6%, 8.5% and 1.7% respectively, whose differences were statistically significant (all P=0.000). Multivariate analysis showed that tumor staging (P=0.005), radical resection (P=0.009), lymphatic or venous invasion (P=0.017) and postoperative chemotherapy (P=0.001) were independent prognostic factors. Surgical treatment for Borrmann type IIII( gastric cancer involving the whole stomach is safe. Radical resection can improve the prognosis though the overall survival is poor.

Assessing hospitals' clinical risk management: Development of a monitoring instrument

PubMed Central

2010-01-01

Background Clinical risk management (CRM) plays a crucial role in enabling hospitals to identify, contain, and manage risks related to patient safety. So far, no instruments are available to measure and monitor the level of implementation of CRM. Therefore, our objective was to develop an instrument for assessing CRM in hospitals. Methods The instrument was developed based on a literature review, which identified key elements of CRM. These elements were then discussed with a panel of patient safety experts. A theoretical model was used to describe the level to which CRM elements have been implemented within the organization. Interviews with CRM practitioners and a pilot evaluation were conducted to revise the instrument. The first nationwide application of the instrument (138 participating Swiss hospitals) was complemented by in-depth interviews with 25 CRM practitioners in selected hospitals, for validation purposes. Results The monitoring instrument consists of 28 main questions organized in three sections: 1) Implementation and organizational integration of CRM, 2) Strategic objectives and operational implementation of CRM at hospital level, and 3) Overview of CRM in different services. The instrument is available in four languages (English, German, French, and Italian). It allows hospitals to gather comprehensive and systematic data on their CRM practice and to identify areas for further improvement. Conclusions We have developed an instrument for assessing development stages of CRM in hospitals that should be feasible for a continuous monitoring of developments in this important area of patient safety. PMID:21144039

New Technique for Liver Resection Using Heat Coagulative Necrosis

PubMed Central

Weber, Jean-Christophe; Navarra, Giuseppe; Jiao, Long R.; Nicholls, Joanna P.; Jensen, Steen Lindkaer; Habib, Nagy A.

2002-01-01

Objective To assess a new bloodless technique using radiofrequency energy for segmental liver resection of hepatic tumors. Summary Background Data Liver resection remains a formidable surgical procedure; safe performance requires a high level of training and skill. Intraoperative blood loss during liver resection remains a major concern because it is associated with a higher rate of postoperative complications and shorter long-term survival. Methods From January 2000 to June 2001, 15 patients with various hepatic tumors were operated on using radiofrequency energy to remove the tumor in its entirety. Radiofrequency energy was applied along the margins of the tumor to create “zones of necrosis” before resection with a scalpel. Results No blood transfusions were required. The mean blood loss during resection was 30 ± 10 mL. No mortality or morbidity was observed. The median postoperative stay was 8 days (range 5–9). No liver recurrence was detected in patients undergoing resection with this technique during follow-up periods ranging from 2 to 20 months. Conclusions Segmental and wedge liver resection assisted by radiofrequency is safe. This novel technique offers a new method for transfusion-free resection. PMID:12409660

Development and evaluation of a connective tissue phantom model for subsurface visualization of cancers requiring wide local excision.

PubMed

Samkoe, Kimberley S; Bates, Brent D; Tselepidakis, Niki N; DSouza, Alisha V; Gunn, Jason R; Ramkumar, Dipak B; Paulsen, Keith D; Pogue, Brian W; Henderson, Eric R

2017-12-01

Wide local excision (WLE) of tumors with negative margins remains a challenge because surgeons cannot directly visualize the mass. Fluorescence-guided surgery (FGS) may improve surgical accuracy; however, conventional methods with direct surface tumor visualization are not immediately applicable, and properties of tissues surrounding the cancer must be considered. We developed a phantom model for sarcoma resection with the near-infrared fluorophore IRDye 800CW and used it to iteratively define the properties of connective tissues that typically surround sarcoma tumors. We then tested the ability of a blinded surgeon to resect fluorescent tumor-simulating inclusions with ∼1-cm margins using predetermined target fluorescence intensities and a Solaris open-air fluorescence imaging system. In connective tissue-simulating phantoms, fluorescence intensity decreased with increasing blood concentration and increased with increasing intralipid concentrations. Fluorescent inclusions could be resolved at ≥1-cm depth in all inclusion concentrations and sizes tested. When inclusion depth was held constant, fluorescence intensity decreased with decreasing volume. Using targeted fluorescence intensities, a blinded surgeon was able to successfully excise inclusions with ∼1-cm margins from fat- and muscle-simulating phantoms with inclusion-to-background contrast ratios as low as 2∶1. Indirect, subsurface FGS is a promising tool for surgical resection of cancers requiring WLE. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

A non-canonical mechanism for Crm1-export cargo complex assembly

PubMed Central

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Boulos Faza, Marius; Panse, Vikram Govind

2015-01-01

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export. DOI: http://dx.doi.org/10.7554/eLife.05745.001 PMID:25895666

A fraction of Crm1 locates at centrosomes by its CRIME domain and regulates the centrosomal localization of pericentrin

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

Liu, Qinying; Jiang, Qing; Zhang, Chuanmao, E-mail: zhangcm@pku.edu.cn

Crm1 plays a role in exporting proteins containing nuclear export signals (NESs) from the nucleus to the cytoplasm. Some proteins that are capable of interacting with Ran/Crm1 were reported to be localized at centrosomes and to function as centrosome checkpoints. But it remains unclear how Crm1 locates at centrosomes. In this study, we found that a fraction of Crm1 is located at centrosomes through its N-terminal CRM1, importin {beta} etc. (CRIME) domain, which is responsible for interacting with RanGTP, suggesting that Crm1 might target to centrosomes through binding centrosomal RanGTP. Moreover, overexpression of the CRIME domain, which is free ofmore » NES binding domain, resulted in the dissociation of pericentrin and {gamma}-tubulin complex from centrosomes and the disruption of microtubule nucleation. Deficiency of Crm1 provoked by RNAi also decreased the spindle poles localization of pericentrin and {gamma}-tubulin complex, coupled with mitotic defects. Since pericentrin was sensitive to Crm1 specific inhibitor leptomycin B, we propose that the centrosomal Crm1 might interact with pericentrin and regulate the localization and function of pericentrin at centrosomes.« less

Filling the Gap: Simulation-based Crisis Resource Management Training for Emergency Medicine Residents.

PubMed

Parsons, Jessica R; Crichlow, Amanda; Ponnuru, Srikala; Shewokis, Patricia A; Goswami, Varsha; Griswold, Sharon

2018-01-01

In today's team-oriented healthcare environment, high-quality patient care requires physicians to possess not only medical knowledge and technical skills but also crisis resource management (CRM) skills. In emergency medicine (EM), the high acuity and dynamic environment makes CRM skills of physicians particularly critical to healthcare team success. The Accreditation Council of Graduate Medicine Education Core Competencies that guide residency program curriculums include CRM skills; however, EM residency programs are not given specific instructions as to how to teach these skills to their trainees. This article describes a simulation-based CRM course designed specifically for novice EM residents. The CRM course includes an introductory didactic presentation followed by a series of simulation scenarios and structured debriefs. The course is designed to use observational learning within simulation education to decrease the time and resources required for implementation. To assess the effectiveness in improving team CRM skills, two independent raters use a validated CRM global rating scale to measure the CRM skills displayed by teams of EM interns in a pretest and posttest during the course. The CRM course improved leadership, problem solving, communication, situational awareness, teamwork, resource utilization and overall CRM skills displayed by teams of EM interns. While the improvement from pretest to posttest did not reach statistical significance for this pilot study, the large effect sizes suggest that statistical significance may be achieved with a larger sample size. This course can feasibly be incorporated into existing EM residency curriculums to provide EM trainees with basic CRM skills required of successful emergency physicians. We believe integrating CRM training early into existing EM education encourages continued deliberate practice, discussion, and improvement of essential CRM skills.

Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases - Pushing growth as an independent risk factor for decreased survival.

PubMed

Falcão, Daniela; Alexandrino, Henrique; Caetano Oliveira, Rui; Martins, João; Ferreira, Luís; Martins, Ricardo; Serôdio, Marco; Martins, Mónica; Tralhão, José Guilherme; Cipriano, Maria Augusta; Castro E Sousa, Francisco

2018-04-11

Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Comparison of intracorporeal single-stapled and double-stapled anastomosis in laparoscopic low anterior resection for rectal cancer: a case-control study.

PubMed

Kim, Hye Jin; Choi, Gyu-Seog; Park, Jun Seok; Park, Soo Yeun

2013-01-01

Recently, a single-stapled technique (SST) was performed instead of the conventional double-stapled technique (DST) in laparoscopic low anterior resection for anastomosis, by placement of intracorporeal purse-string sutures on the distal rectum with transanal specimen extraction. This study aimed to compare the short-term outcomes between the two anastomotic techniques. Between July 2007 and April 2010, 60 patients underwent SST by laparoscopic or robotic procedure. These patients were matched 1:2 by age, gender, date of surgery, and tumor stage with 120 patients who underwent conventional DST in laparoscopic low anterior resection. The robotic-assisted operative approach was used more frequently in the SST group than in the DST group (61.7 % vs. 3.3 %, p < 0.001). The mean operative time was 203.9 (range, 120-400) min for the SST group and 167.6 (range, 90-300) min for the DST group (p < 0.001). For specimen removal, the transanal approach was used in the SST group, while the transabdominal approach was used for the DST group. The pain score (visual analogue scale) of the SST group was lower (4.5 vs. 5.6, p < 0.001), although postoperative recovery was similar. Pathological examination revealed that the distal resection margin was significantly longer in the SST group (3.1 vs. 2.5 cm, p = 0.018). Postoperative morbidity including anastomotic leakage was similar in both groups. SST yielded equivalent short-term outcomes when compared to conventional DST and provided the advantages of minimal access and a longer distal resection margin. Therefore, SST in lower anterior resection may be a useful alternative to conventional DST.

Management of non metastatic phyllodes tumors of the breast: review of the literature.

PubMed

Khosravi-Shahi, Parham

2011-12-01

Phyllodes tumors of the breast are rare tumors, accounting for less than 0.5% of all breast tumors. These tumors are comprised of both stromal and epithelial elements; and traditionally they are graded by the use of a set of histologic features into benign, borderline, and malignant subtypes. Unfortunately, the histologic classification of phyllodes tumors does not reliably predict clinical behavior. The mainstay of treatment of non metastatic phyllodes tumors of the breast is complete surgical resection with wide resection margins. Lumpectomy or partial mastectomy is the preferred surgical therapy. However, despite the complete surgical resection, local failure rate may be high; and 22% of malignant tumors may give rise to haematogenous metastases. The most frequent site of distant metastases is the lungs. Several predictive factors of recurrence and metastases have been described in the literature, such as positive surgical margins, increased stromal cellularity, stromal overgrowth, stromal atypia and increased mitotic activity. Nevertheless, the role of adjuvant therapies (radiotherapy and chemotherapy) is presently undefined and should be tested in multicenter, prospective, randomized trials. Copyright © 2011 Elsevier Ltd. All rights reserved.

Economic Implications of Widespread Expansion of Frozen Section Margin Analysis to Guide Surgical Resection in Women With Breast Cancer Undergoing Breast-Conserving Surgery.

PubMed

Boughey, Judy C; Keeney, Gary L; Radensky, Paul; Song, Christine P; Habermann, Elizabeth B

2016-04-01

In the current health care environment, cost effectiveness is critically important in policy setting and care of patients. This study performed a health economic analysis to assess the implications to providers and payers of expanding the use of frozen section margin analysis to minimize reoperations for patients undergoing breast cancer lumpectomy. A health care economic impact model was built to assess annual costs associated with breast lumpectomy procedures with and without frozen section margin analysis to avoid reoperation. If frozen section margin analysis is used in 20% of breast lumpectomies and under a baseline assumption that 35% of initial lumpectomies without frozen section analysis result in reoperations, the potential annual cost savings are $18.2 million to payers and $0.4 million to providers. Under the same baseline assumption, if 100% of all health care facilities adopted the use of frozen section margin analysis for breast lumpectomy procedures, the potential annual cost savings are $90.9 million to payers and $1.8 million to providers. On the basis of 10,000 simulations, use of intraoperative frozen section margin analysis yields cost saving for payers and is cost neutral to slightly cost saving for providers. This economic analysis indicates that widespread use of frozen section margin evaluation intraoperatively to guide surgical resection in breast lumpectomy cases and minimize reoperations would be beneficial to cost savings not only for the patient but also for payers and, in most cases, for providers. Copyright © 2016 by American Society of Clinical Oncology.

Laparoscopic vs open total mesorectal excision for rectal cancer: an evaluation of the mesorectum's macroscopic quality.

PubMed

Breukink, S O; Grond, A J K; Pierie, J P E N; Hoff, C; Wiggers, T; Meijerink, W J H J

2005-03-01

Next to surgical margins, yield of lymph nodes, and length of bowel resected, macroscopic completeness of mesorectal excision may serve as another quality control of total mesorectal excision (TME). In this study, the macroscopic completeness of laparoscopic TME was evaluated. A series of 25 patients with rectal cancer were managed laparoscopically (LTME) and included in this study. The pathologic specimens of the LTME group were prospectively examined and matched with a historical group of resection specimens from patients who had undergone open TME (OTME). The two groups were matched for gender and type of resection (low anterior or abdominoperineal resection). Special care was given to the macroscopic judgment concerning the completeness of the mesorectum. A three-grade scoring system showed no differences between the LTME and OTME groups. The current study supports the hypothesis that oncologic resection using laparoscopic TME is feasible and adequate.

Outcomes following attempted en bloc resection of cervical chordomas in the C-1 and C-2 region versus the subaxial region: a multiinstitutional experience.

PubMed

Molina, Camilo A; Ames, Christopher P; Chou, Dean; Rhines, Laurence D; Hsieh, Patrick C; Zadnik, Patricia L; Wolinsky, Jean-Paul; Gokaslan, Ziya L; Sciubba, Daniel M

2014-09-01

Chordomas involving the mobile spine are ideally managed via en bloc resection with reconstruction to optimize local control and possibly offer cure. In the cervical spine, local anatomy poses unique challenges, limiting the feasibility of aggressive resection. The authors present a multi-institutional series of 16 cases of cervical chordomas removed en bloc. Particular attention was paid to clinical outcome, complications, and recurrence. In addition, outcomes were assessed according to position of tumor at the C1-2 level versus the subaxial (SA) spine (C3-7). The authors reviewed cases involving patients who underwent en bloc resection of cervical chordoma at 4 large spine centers. Patients were included if the lesion epicenter involved the C-1 to C-7 vertebral bodies. Demographic data and details of surgery, follow-up course, exposure to adjuvant therapy, and complications were obtained. Outcome was correlated with presence of tumor in C1-2 versus subaxial spine via a Student t-test. Sixteen patients were identified (mean age at presentation 55 ± 14 years). Seven cases (44%) cases involved C1-2, and 16 involved the subaxial spine. Median survival did not differ significantly different between the C1-2 (72 months) and SA (60 months) groups (p = 0.65). A combined (staged anteroposterior) approach was used in 81% of the cases. Use of the combined approach was significantly more common in treatment of subaxial than C1-2 tumors (100% vs 57%, p = 0.04). En bloc resection was attempted via an anterior approach in 6% of cases (C1-2: 14.3%; SA: 0%; p = 0.17) and a posterior approach in 13% of cases (C1-2: 29%; SA: 0%; p = 0.09). The most commonly reported margin classification was marginal (56% of cases), followed by violated (25%) and wide (19%). En bloc excision of subaxial tumors was significantly more likely to result in marginal margins than excision of C1-2 tumors (C1-2: 29%; SA: 78%; p = 0.03). C1-2 tumors were associated with significantly higher rates of postoperative complications (C1-2: 71%; SA: 22%; p = 0.03). Both local and distant tumor recurrence was greatest for C1-2 tumors (local C1-2: 29%; local SA: 11%; distant C1-2: 14%; distant SA: 0%). Statistical analysis of tumor recurrence based on tumor location was not possible due to the small number of cases. There was no between-groups difference in exposure to postoperative adjuvant radiotherapy. There was no difference in median survival between groups receiving proton beam radiotherapy or intensity-modulated radiotherapy versus no radiation therapy (p = 0.8). Compared with en bloc resection of chordomas involving the subaxial cervical spine, en bloc resection of chordomas involving the upper cervical spine (C1-2) is associated with poorer outcomes, such as less favorable margins, higher rates of complications, and increased tumor recurrence. Data from this cohort do not support a statistically significant difference in survival for patients with C1-2 versus subaxial disease, but larger studies are needed to further study survival differences.

Local resection of the stomach for gastric cancer.

PubMed

Kinami, Shinichi; Funaki, Hiroshi; Fujita, Hideto; Nakano, Yasuharu; Ueda, Nobuhiko; Kosaka, Takeo

2017-06-01

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.

Margins in Skin Excision Biopsies: Principles and Guidelines

PubMed Central

Ranjan, Richa; Singh, Lavleen; Arava, Sudheer K; Singh, Manoj Kumar

2014-01-01

Skin biopsies are usually undertaken to confirm a clinical diagnosis, to remove a lesion, and to determine the adequacy of excised tissue margin. A surgical margin is technically defined as the “edge” of the tissue removed. The term is especially pertinent when the tissue excised is suspected of being involved by a malignant process. One of the most important predictive and prognostic factors of a malignant lesion is whether the margins of the resected specimen are involved by the tumor or not. The purpose of this review is to provide an insight into grossing of a skin biopsy specimen with emphasis on techniques and reporting of excision biopsy margins. PMID:25484385

Histopathological Validation of the Surface-Intermediate-Base Margin Score for Standardized Reporting of Resection Technique during Nephron Sparing Surgery.

PubMed

Minervini, Andrea; Campi, Riccardo; Kutikov, Alexander; Montagnani, Ilaria; Sessa, Francesco; Serni, Sergio; Raspollini, Maria Rosaria; Carini, Marco

2015-10-01

The surface-intermediate-base margin score is a novel standardized reporting system of resection techniques during nephron sparing surgery. We validated the surgeon assessed surface-intermediate-base score with microscopic histopathological assessment of partial nephrectomy specimens. Between June and August 2014 data were prospectively collected from 40 consecutive patients undergoing nephron sparing surgery. The surface-intermediate-base score was assigned to all cases. The score specific areas were color coded with tissue margin ink and sectioned for histological evaluation of healthy renal margin thickness. Maximum, minimum and mean thickness of healthy renal margin for each score specific area grade (surface [S] = 0, S = 1 ; intermediate [I] or base [B] = 0, I or B = 1, I or B = 2) was reported. The Mann-Whitney U and Kruskal-Wallis tests were used to compare the thickness of healthy renal margin in S = 0 vs 1 and I or B = 0 vs 1 vs 2 grades, respectively. Maximum, minimum and mean thickness of healthy renal margin was significantly different among score specific area grades S = 0 vs 1, and I or B = 0 vs 1, 0 vs 2 and 1 vs 2 (p <0.001). The main limitations of the study are the low number of the I or B = 1 and I or B = 2 samples and the assumption that each microscopic slide reflects the entire score specific area for histological analysis. The surface-intermediate-base scoring method can be readily harnessed in real-world clinical practice and accurately mirrors histopathological analysis for quantification and reporting of healthy renal margin thickness removed during tumor excision. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Immunogenicity of MenACWY-CRM in Korean Military Recruits: Influence of Tetanus-Diphtheria Toxoid Vaccination on the Vaccine Response to MenACWY-CRM.

PubMed

Kim, Han Wool; Park, In Ho; You, Sooseong; Yu, Hee Tae; Oh, In Soo; Sung, Pil Soo; Shin, Eui Cheol; Kim, Kyung Hyo

2016-11-01

The quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) has been introduced for military recruits in Korea since 2012. This study was performed to evaluate the immunogenicity of MenACWY-CRM in Korean military recruits. In addition, the influence of tetanus-diphtheria toxoids (Td) vaccination on the vaccine response to MenACWY-CRM was analyzed. A total of 75 military recruits were enrolled. Among them, 18 received a dose of MenACWY-CRM only (group 1), and 57 received Td three days before MenACWY-CRM immunization (group 2). The immunogenicity of MenACWY-CRM was compared between the two groups. The serum bactericidal activity with baby rabbit complement was measured before and three weeks after immunization against serogroups A, C, W-135, and Y. The geometric mean titers (GMTs) against four serogroups were significantly increased in both groups after immunization. Compared to group 2, group 1 exhibited significantly higher vaccine responses in several aspects: post-immune GMTs against serogroup A and C, seroresponse rates against serogroup A, and a fold increases of titers against serogroup A, C, and Y. MenACWY-CRM was immunogenic against all vaccine-serogroups in Korean military recruits. Vaccine response to MenACWY-CRM was influenced by Td administered three days earlier.

A cellular reporter to evaluate CRM1 nuclear export activity: functional analysis of the cancer-related mutant E571K.

PubMed

García-Santisteban, Iraia; Arregi, Igor; Alonso-Mariño, Marián; Urbaneja, María A; Garcia-Vallejo, Juan J; Bañuelos, Sonia; Rodríguez, Jose A

2016-12-01

The exportin CRM1 binds nuclear export signals (NESs), and mediates active transport of NES-bearing proteins from the nucleus to the cytoplasm. Structural and biochemical analyses have uncovered the molecular mechanisms underlying CRM1/NES interaction. CRM1 binds NESs through a hydrophobic cleft, whose open or closed conformation facilitates NES binding and release. Several cofactors allosterically modulate the conformation of the NES-binding cleft through intramolecular interactions involving an acidic loop and a C-terminal helix in CRM1. This current model of CRM1-mediated nuclear export has not yet been evaluated in a cellular setting. Here, we describe SRV100, a cellular reporter to interrogate CRM1 nuclear export activity. Using this novel tool, we provide evidence further validating the model of NES binding and release by CRM1. Furthermore, using both SRV100-based cellular assays and in vitro biochemical analyses, we investigate the functional consequences of a recurrent cancer-related mutation, which targets a residue near CRM1 NES-binding cleft. Our data indicate that this mutation does not necessarily abrogate the nuclear export activity of CRM1, but may increase its affinity for NES sequences bearing a more negatively charged C-terminal end.

Single-stage anterior high sacrectomy for locally recurrent rectal cancer.

PubMed

Fawaz, Khaled; Khaled, Fawaz; Smith, Myles J; Moises, Cukier; Smith, Andrew J; Yee, Albert J M

2014-03-01

A review of prospectively collected data on a consecutive series of patients undergoing single-stage anterior high sacrectomy for locally recurrent rectal carcinoma (LRRC). To determine the clinical outcome of patients who underwent anterior high sacrectomy for LRRC. High sacrectomy for oncological resection remains technically challenging. Surgery has the potential to achieve cure in carefully selected patients. Complete (R0) tumor excision in LRRC may require sacrectomy. High sacral resections (S3 and above) typically require a combined anterior/supine and posterior/prone procedure. We investigated our experience performing single-stage anterior high sacrectomy for LRRC. A consecutive series of patients with LRRC without systemic metastases who underwent resection with curative intent requiring high sacrectomy were identified. A review of a prospectively maintained colorectal and spine cancer database data was performed. An oblique dome high sacral osteotomy was performed during a single-stage anterior procedure. Outcome measures included surgical resection margin status, hospital length of stay, postoperative complications, physical functioning status, and overall survival. Nineteen consecutive patients were treated between 2002 and 2011. High sacrectomy was performed at sacral level S1-S2 in 4 patients, S2-S3 in 9 patients, and through S3 in 6 patients. An R0 resection margin was achieved histologically in all 19 cases. There was 1 early (<30 d) postoperative death (1/19, 5%). At median follow-up of 38 months, 13 patients had no evidence of residual disease, 1 was alive with disease, and 4 had died of disease. Morbidities occurred in 15 of the 19 patients (79%). Although high sacrectomy may require a combined anterior and posterior surgical approach, our series demonstrates the feasibility of performing single-stage anterior high sacrectomy in LRRC, with acceptable risks and outcomes compared with the literature. The procedure described by us for LRRC lessens the need for a simultaneous or staged prone posterior resection, with favorable R0 tumor resections, patient survival, and clinical outcomes. N/A.

Role of intraoperative radiotherapy in the treatment of sacral chordoma.

PubMed

Jullien-Petrelli, Ariel Christian; García-Sabrido, J L; Orue-Echebarria, M I; Lozano, P; Álvarez, A; Serrano, J; Calvo, F M; Calvo-Haro, J A; Lasso, J M; Asencio, J M

2018-04-01

Sacral chordoma is a rare entity with high local recurrence rates when complete resection is not achieved. To date, there are no series available in literature combining surgery and intraoperative radiotherapy (IORT). The objective of this study was to report the experience of our center in the management of sacral chordoma combining radical resection with both external radiotherapy and IORT. This is a retrospective case series. The patient sample included 15 patients with sacral chordoma resected in our center from 1998 to 2015. The outcome measures were overall survival (OS), disease-free survival (DFS), and rates of local and distant recurrences. We retrospectively reviewed the records of all the patients with sacral chordoma resected in our center from 1998 to December 2015. Overall survival, DFS, and rates of local and distant recurrences were calculated. Results between patients treated with or without IORT were compared. A total of 15 patients were identified: 8 men and 7 women. The median age was 59 years (range 28-77). Intraoperative radiotherapy was applied in nine patients and six were treated with surgical resection without IORT. In 13 patients, we performed the treatment of the primary tumor, and in two patients, we performed the treatment of recurrence disease. A posterior approach was used in four patients. Wide surgical margins (zero residue) were achieved in six patients, marginal margins (microscopic residue) were achieved in seven patients, and there were no patients with intralesional (R2) margins. At a median follow-up of 38 months (range 11-209 months), the 5-year OS in the IORT group was 100% versus 53% in the group of non-IORT (p=.05). The median DFS in the IORT group was 85 months, and that in the non-IORT group was 41 months. In the group without IORT, two patients died and nobody died during the follow-up in the group treated with IORT. High-sacrectomy treated patients had a median survival of 41 months, and low-sacrectomy treated patients had a median survival of 90 months. Disease-free survival in patients without gluteal involvement was 100% at 5 years, and that in patients with gluteal involvement was 40%. All patients with a recurrence in our study had gluteal involvement. Multidisciplinary management of sacral chordoma seems to improve local control. The use of IORT, in our experience, is associated with an increase in OS and DFS. The level of resection and gluteal involvement seems to affect survival. The posterior approach is useful in selected cases. Multicenter studies should be performed to confirm the utility of IORT. Copyright © 2017 Elsevier Inc. All rights reserved.

77 FR 20010 - Proposed Information Collection; Comment Request; Online Customer Relationship Management (CRM...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-03

... DEPARTMENT OF COMMERCE Minority Business Development Agency Proposed Information Collection; Comment Request; Online Customer Relationship Management (CRM)/Performance Databases, the Online Phoenix... of program goals via the Online CRM/Performance Databases. The data collected through the Online CRM...

Endoscopic submucosal dissection for locally recurrent colorectal lesions after previous endoscopic mucosal resection.

PubMed

Zhou, Pinghong; Yao, Liqing; Qin, Xinyu; Xu, Meidong; Zhong, Yunshi; Chen, Weifeng

2009-02-01

The objective of this study was to determine the efficacy and safety of endoscopic submucosal dissection for locally recurrent colorectal cancer after previous endoscopic mucosal resection. A total of 16 patients with locally recurrent colorectal lesions were enrolled. A needle knife, an insulated-tip knife and a hook knife were used to resect the lesion along the submucosa. The rate of the curative resection, procedure time, and incidence of complications were evaluated. Of 16 lesions, 15 were completely resected with endoscopic submucosal dissection, yielding an en bloc resection rate of 93.8 percent. Histologic examination confirmed that lateral and basal margins were cancer-free in 14 patients (87.5 percent). The average procedure time was 87.2 +/- 60.7 minutes. None of the patients had immediate or delayed bleeding during or after endoscopic submucosal dissection. Perforation in one patient (6.3 percent) was the only complication and was managed conservatively. The mean follow-up period was 15.5 +/- 6.8 months; none of the patients experienced lesion residue or recurrence. Endoscopic submucosal dissection appears to be effective for locally recurrent colorectal cancer after previous endoscopic mucosal resection, making it possible to resect whole lesions and provide precise histologic information.

Acquisition of chemical remanent magnetization during experimental ferrihydrite-hematite conversion in Earth-like magnetic field-implications for paleomagnetic studies of red beds

NASA Astrophysics Data System (ADS)

Jiang, Zhaoxia; Liu, Qingsong; Dekkers, Mark J.; Tauxe, Lisa; Qin, Huafeng; Barrón, Vidal; Torrent, José

2015-10-01

Hematite-bearing red beds are renowned for their chemical remanent magnetization (CRM). If the CRM was acquired substantially later than the sediment was formed, this severely compromises paleomagnetic records. To improve our interpretation of the natural remanent magnetization, the intricacies of the CRM acquisition process must be understood. Here, we contribute to this issue by synthesizing hematite under controlled 'Earth-like' field conditions (≲ 100 μ T). CRM was imparted in 90 oriented samples with varying inclinations. The final synthesis product appeared to be dominated by hematite with traces of ferrimagnetic iron oxides. When the magnetic field intensity is ≳ 40 μ T, the CRM records the field direction faithfully. However, for field intensities ≲ 40 μ T, the CRM direction may deviate considerably from that of the applied field during synthesis. The CRM intensity normalized by the isothermal remanent magnetization (CRM/IRM@2.5 T) increases linearly with the intensity of growth field, implying that CRM could potentially be useful for relative paleointensity studies if hematite particles of chemical origins have consistent properties. CRM in hematite has a distributed unblocking temperature spectrum from ∼200 to ∼650 °C, while hematite with a depositional remanent magnetization (DRM) has a more confined spectrum from ∼ 600to 680 °C because it is usually coarser-grained and more stoichiometric. Therefore, the thermal decay curves of CRM with their concave shape are notably different from their DRM counterparts which are convex. These differences together are suggested to be a potential discriminator of CRM from DRM carried by hematite in natural red beds, and of significance for the interpretation of paleomagnetic studies on red beds.

Tailored Treatment Strategy for Locally Advanced Rectal Carcinoma Based on the Tumor Response to Induction Chemotherapy: Preliminary Results of the French Phase II Multicenter GRECCAR4 Trial.

PubMed

Rouanet, Philippe; Rullier, Eric; Lelong, Bernard; Maingon, Philippe; Tuech, Jean-Jacques; Pezet, Denis; Castan, Florence; Nougaret, Stéphanie

2017-07-01

Preoperative radiochemotherapy and total mesorectal excision are the standard-of-care for locally advanced rectal carcinoma, but some patients could be over- or undertreated. This study aimed to assess the feasibility of radiochemotherapy tailored based on the tumor response to induction chemotherapy (FOLFIRINOX) to obtain a minimum R0 resection rate of 90% in the 4 arms of the study. This study is a multicenter randomized trial (NCT01333709). This study was conducted at 16 French cancer specialty centers. Two hundred six patients with locally advanced rectal carcinoma were enrolled between 2011 and 2014. Good responders (≥75% tumor volume reduction) were randomly assigned to immediate surgery (arm A) or standard radiochemotherapy (Cap 50: 50 Gy irradiation and 1600 mg/m oral capecitabine daily) plus surgery (arm B). Poor responders were randomly assigned to Cap 50 (arm C) or intensive radiochemotherapy (Cap 60, 60 Gy irradiation, arm D) before surgery. The primary end point was a R0 resection rate (circumferential resection margin >1 mm). The experimental strategies were to be considered effective if at least 28 successes (R0 resection) among 31 patients in each arm of stratum I and 34 successes among 40 patients in each arm of stratum II were reported (Simon 2-stage design). After induction treatment (good compliance), 194 patients were classified as good (n = 30, 15%) or poor (n = 164, 85%) responders who were included in arms A and B (16 and 14 patients) and arms C and D (113 and 51 patients). The trial was prematurely stopped because of low accrual in arms A and B and recruitment completion in arms C and D. Data from 133 randomly assigned patients were analyzed: 11, 19, 52, and 51 patients in arms A, B, C, and D. Good responders had smaller tumors than poor responders (23 cm vs 45 cm; p < 0.001). The surgical procedure was similar among groups. The R0 resection rates [90% CI] were 100% [70-100], 100% [85-100], 83% [72-91], and 88% [77-95]. Among the first 40 patients, 34 successes were reported in arms C and D (85% R0 resection rate). The circumferential resection margin ≤1 rates were 0%, 0%, 12%, and 5% in arms A, B, C, and D. The rate of transformation from positive to negative circumferential resection margin was 93%. There was low accrual in arms A and B. Tailoring preoperative radiochemotherapy based on the induction treatment response appears safe for poor responders and promising for good responders. Long-term clinical results are needed to confirm its efficacy. See Video Abstract at http://links.lww.com/DCR/A359.

Clinical usefulness of extending the proximal margin in total gastrectomies for gastric adenocarcinoma.

PubMed

Clemente-Gutiérrez, U; Sánchez-Morales, G; Santes, O; Medina-Franco, H

2018-05-09

Surgical resection with negative margins is part of the curative treatment of gastric adenocarcinoma. Positive surgical margins are associated with worse outcome. The aim of the present study was to determine the clinical usefulness of extending the proximal surgical margin in patients undergoing total gastrectomy for gastric adenocarcinoma. A retrospective analysis of patients that underwent total gastrectomy within the time frame of 2002 and 2017 was conducted. Patients diagnosed with adenocarcinoma that underwent curative surgery were included. Patients were divided into three groups, depending on proximal surgical margin status: negative margin (R0), positive margin with additional resection to achieve negative margin (R1-R0), and positive margin (R1). Demographic and clinical variables were analyzed. The outcome measures to evaluate were recurrence, disease-free survival, and overall survival. Forty-eight patients were included in the study. Thirty-seven were classified as R0, 9 as R1-R0, and 2 as R1. Fifty-two percent of the patients had clinical stage III disease. The overall surgical mortality rate was 2% and the morbidity rate was higher than 29%. The local recurrence rate was 0% in the R1-R0 group vs. 50% in the R1 group (p = 0.02). Disease-free survival was 49 months in the R1-R0 group vs. 32 months in the R1 group (p = 0.6). Overall survival was 51 months for the R1-R0 group vs. 35 months for the R1 group (p = 0.5). Intraoperative extension of the positive surgical margin improved the local recurrence rate but was not associated with improvement in overall survival or disease-free survival and could possibly increase postoperative morbidity. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

CRM - I Want It My Way!

NASA Technical Reports Server (NTRS)

Henwood, Bart

2007-01-01

This viewgraph presentation provides an overview of crew resource management (CRM). Topics include what makes a good participant in a team process, human perception and response of individual behavior, characteristics of a bad participant, factors that affect performance, CRM assumptions and techniques, and CRM and individuality.

NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1.

PubMed

Güttler, Thomas; Madl, Tobias; Neumann, Piotr; Deichsel, Danilo; Corsini, Lorenzo; Monecke, Thomas; Ficner, Ralf; Sattler, Michael; Görlich, Dirk

2010-11-01

Classic nuclear export signals (NESs) confer CRM1-dependent nuclear export. Here we present crystal structures of the RanGTP-CRM1 complex alone and bound to the prototypic PKI or HIV-1 Rev NESs. These NESs differ markedly in the spacing of their key hydrophobic (Φ) residues, yet CRM1 recognizes them with the same rigid set of five Φ pockets. The different Φ spacings are compensated for by different conformations of the bound NESs: in the case of PKI, an α-helical conformation, and in the case of Rev, an extended conformation with a critical proline docking into a Φ pocket. NMR analyses of CRM1-bound and CRM1-free PKI NES suggest that CRM1 selects NES conformers that pre-exist in solution. Our data lead to a new structure-based NES consensus, and explain why NESs differ in their affinities for CRM1 and why supraphysiological NESs bind the exportin so tightly.

Meta-analysis and cost effective analysis of portal-superior mesenteric vein resection during pancreatoduodenectomy: Impact on margin status and survival.

PubMed

Bell, Richard; Ao, Braden Te; Ironside, Natasha; Bartlett, Adam; Windsor, John A; Pandanaboyana, Sanjay

2017-03-01

The benefit of portal-superior mesenteric vein resection (PSMVR) with pancreatoduodenectomy (PD) remains controversial. This study assesses the impact of PSMVR on resection margin status and survival. An electronic search was performed to identify relevant articles. Pooled odds ratios were calculated for outcomes using the fixed or random-effects models for meta-analysis. A decision analytical model was developed for estimating cost effectiveness. Sixteen studies with 4145 patients who underwent pancreatoduodenectomy were included: 1207 patients had PSMVR and 2938 patients had no PSMVR. The R1 resection rate and post-operative mortality was significantly higher in PSMVR group (OR1.59[1.35, 1.86] p=<0.0001, and OR1.72 [1.02,2.92] p = 0.04 respectively). The overall survival at 5-years was worse in the PSMVR group (HR0.20 [0.07,0.55] P = 0.020). Tumour size (p = 0.030) and perineural invasion (P = 0.009) were higher in the PSMVR group. Not performing PSMVR yielded cost savings of $1617 per additional month alive without reduction in overall outcome. On the basis of retrospective data this study shows that PD with PSMVR is associated with a higher R1 rate, lower 5-year survival and is not cost-effective. It appears that PD with PSMVR can only be justified if R0 resection can be achieved. The continuing challenge is accurate selection of these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Laparoscopic versus robotic surgery for hepatocellular carcinoma: the first 46 consecutive cases.

PubMed

Magistri, Paolo; Tarantino, Giuseppe; Guidetti, Cristiano; Assirati, Giacomo; Olivieri, Tiziana; Ballarin, Roberto; Coratti, Andrea; Di Benedetto, Fabrizio

2017-09-01

Hepatocellular carcinoma has a growing incidence worldwide, and represents a leading cause of death in patients with cirrhosis. Nowadays, minimally invasive approaches are spreading in every field of surgery and in liver surgery as well. We retrospectively reviewed demographics, clinical, and pathologic characteristics and short-term outcomes of patients who had undergone minimally invasive resections for hepatocellular carcinoma at our institution between June 2012 and May 2016. No significant differences in demographics and comorbidities were found between patients in the laparoscopic (n = 24) and robotic (n = 22) groups, except for the rates of cirrhotic patients (91.7% and 68.2%, respectively, P = 0.046). Perioperative data analysis showed that the operative time (mean, 211 and 318 min, respectively, P < 0.001) was the only parameter in favor of laparoscopy. Conversely, robotic-assisted resections were related to less Clavien I-II postoperative complications (22 cases versus 13 cases; P = 0.03). As regards resection margins, the two groups were similar with no statistically significant differences in rates of disease-free resection margins. A modern hepatobiliary center should offer both open and minimally invasive approaches to liver disease to provide the best care for each patient, according to the individual comorbidities, risk factors, and personal quality of life expectations. Our results show that the robotic approach is a reliable tool for accurate oncologic surgery, comparable to the laparoscopic approach. Robotic surgery also allows the surgeon to safely approach liver segments that are difficult to resect in laparoscopy, namely segments I-VII-VIII. Copyright © 2017 Elsevier Inc. All rights reserved.

Hand-assisted Approach as a Model to Teach Complex Laparoscopic Hepatectomies: Preliminary Results.

PubMed

Makdissi, Fabio F; Jeismann, Vagner B; Kruger, Jaime A P; Coelho, Fabricio F; Ribeiro-Junior, Ulysses; Cecconello, Ivan; Herman, Paulo

2017-08-01

Currently, there are limited and scarce models to teach complex liver resections by laparoscopy. The aim of this study is to present a hand-assisted technique to teach complex laparoscopic hepatectomies for fellows in liver surgery. Laparoscopic hand-assisted approach for resections of liver lesions located in posterosuperior segments (7, 6/7, 7/8, 8) was performed by the trainees with guidance and intermittent intervention of a senior surgeon. Data as: (1) percentage of time that the senior surgeon takes the surgery as main surgeon, (2) need for the senior surgeon to finish the procedure, (3) necessity of conversion, (4) bleeding with hemodynamic instability, (5) need for transfusion, (6) oncological surgical margins, were evaluated. In total, 12 cases of complex laparoscopic liver resections were performed by the trainee. All cases included deep lesions situated on liver segments 7 or 8. The senior surgeon intervention occurred in a mean of 20% of the total surgical time (range, 0% to 50%). A senior intervention >20% was necessary in 2 cases. There was no need for conversion or reoperation. Neither major bleeding nor complications resulted from the teaching program. All surgical margins were clear. This preliminary report shows that hand-assistance is a safe way to teach complex liver resections without compromising patient safety or oncological results. More cases are still necessary to draw definitive conclusions about this teaching method.

A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine.

PubMed

Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France

2008-08-18

CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.

Stereotactic Body Radiation Therapy for Locally Advanced and Borderline Resectable Pancreatic Cancer Is Effective and Well Tolerated

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

Chuong, Michael D.; Springett, Gregory M.; Freilich, Jessica M.

Purpose: Stereotactic body radiation therapy (SBRT) provides high rates of local control (LC) and margin-negative (R0) resections for locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), respectively, with minimal toxicity. Methods and Materials: A single-institution retrospective review was performed for patients with nonmetastatic pancreatic cancer treated with induction chemotherapy followed by SBRT. SBRT was delivered over 5 consecutive fractions using a dose painting technique including 7-10 Gy/fraction to the region of vessel abutment or encasement and 5-6 Gy/fraction to the remainder of the tumor. Restaging scans were performed at 4 weeks, and resectable patients were considered formore » resection. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: Seventy-three patients were evaluated, with a median follow-up time of 10.5 months. Median doses of 35 Gy and 25 Gy were delivered to the region of vessel involvement and the remainder of the tumor, respectively. Thirty-two BRPC patients (56.1%) underwent surgery, with 31 undergoing an R0 resection (96.9%). The median OS, 1-year OS, median PFS, and 1-year PFS for BRPC versus LAPC patients was 16.4 months versus 15 months, 72.2% versus 68.1%, 9.7 versus 9.8 months, and 42.8% versus 41%, respectively (all P>.10). BRPC patients who underwent R0 resection had improved median OS (19.3 vs 12.3 months; P=.03), 1-year OS (84.2% vs 58.3%; P=.03), and 1-year PFS (56.5% vs 25.0%; P<.0001), respectively, compared with all nonsurgical patients. The 1-year LC in nonsurgical patients was 81%. We did not observe acute grade ≥3 toxicity, and late grade ≥3 toxicity was minimal (5.3%). Conclusions: SBRT safely facilitates margin-negative resection in patients with BRPC pancreatic cancer while maintaining a high rate of LC in unresectable patients. These data support the expanded implementation of SBRT for pancreatic cancer.« less

Radiation therapy and surgery for fibrosarcoma in 33 cats.

PubMed

Cronin, K; Page, R L; Spodnick, G; Dodge, R; Hardie, E N; Price, G S; Ruslander, D; Thrall, D E

1998-01-01

Thirty-three cats with histologically confirmed fibrosarcomas were treated with radiation therapy followed by surgery. The median (95% confidence interval) disease free interval and overall survival were 398 (261,924) and 600 (lower limit 515) days, respectively. There were 19 treatment failures; 11 cats had only local recurrence, 4 cats developed metastatic disease, 3 cats had local recurrence followed by metastasis, and 1 cat developed simultaneous local and distant disease. Twelve cats are alive and disease free. Two cats died without evidence of treatment failure. The presence of tumor cells at the margin of resected tissue after radiation was the only variable which influenced treatment success. The median (95% confidence interval) disease free interval in 5 cats with tumor cells at the margin of the resected specimen was 112 (94,150) days versus 700 (lower limit 328) days for 26 cats with negative tumor margins, p < 0.0001. We did not identify a relationship between tumor volume, number of prior tumor excisions, concomitant use of chemotherapy or various descriptors of the radiation therapy technique and disease free interval.

Opening up the solar box: Cultural resource management and actor network theory in solar energy projects in the Mojave Desert

NASA Astrophysics Data System (ADS)

Gorrie, Bryan F.

This project considers the ways that Actor-Network Theory (ANT) can be brought to bear upon Cultural Resource Management (CRM) practices on renewable energy projects. ANT is a way of making inquiry into scientific knowledge practices and as CRM is intended to preserve environmental, historic, and prehistoric resources, it necessarily involves certain kinds of knowledge generation about regions in which projects are being developed. Because the practice of CRM is complex, involving a range of actors from developers to biologists, native peoples to academics, private landholders to environmental and cultural activists, it is imperative to account for the interests of all stakeholders and to resist devolving into the polemical relations of winners and losers, good and bad participants, or simple situations of right and wrong. This project intends to account for the "matters of concern" of various actors, both primary and secondary, by examining the case study of a single solar installation project in the Mojave Desert. A theoretical description of ANT is provided at the beginning and the concerns of this theory are brought to bear upon the case study project through describing the project, discussing the laws governing CRM on federal lands and in the state of California, and providing the points of view of various interviewees who worked directly or indirectly on various aspects of CRM for the solar project. The creators of ANT claim that it is not a methodology but it does speak to ethnomethodologies in that it insists that there is always something more to learn from inquiring into and describing any given situation. These descriptions avoid generalizations, providing instead various points of entry, from diverse perspectives to the project. There is an invitation to avoid assuming that one knows all there is to know about a given situation and to choose instead to continue investigating and thus give voice to the more obscure, often marginalized, voices in the network of actors. With Thomas F. King, I recommend ongoing work that brings the theories ANT provides to bear on specific "matters of concern," which are necessarily contingent and situated, to build acceptance and to "respect the legitimacy of [any given] small group's cultural values -- whether the group is made up of American Indians, cattle ranchers in Montana, or Southern Baptists" (King 2002:xvii) so that cultural resource management work can actualize the meaningful contribution to political and cultural systems that it was intended to facilitate.

Risk factor assessment of endoscopically removed malignant colorectal polyps.

PubMed

Netzer, P; Forster, C; Biral, R; Ruchti, C; Neuweiler, J; Stauffer, E; Schönegg, R; Maurer, C; Hüsler, J; Halter, F; Schmassmann, A

1998-11-01

Malignant colorectal polyps are defined as endoscopically removed polyps with cancerous tissue which has invaded the submucosa. Various histological criteria exist for managing these patients. To determine the significance of histological findings of patients with malignant polyps. Five pathologists reviewed the specimens of 85 patients initially diagnosed with malignant polyps. High risk malignant polyps were defined as having one of the following: incomplete polypectomy, a margin not clearly cancer-free, lymphatic or venous invasion, or grade III carcinoma. Adverse outcome was defined as residual cancer in a resection specimen and local or metastatic recurrence in the follow up period (mean 67 months). Malignant polyps were confirmed in 70 cases. In the 32 low risk malignant polyps, no adverse outcomes occurred; 16 (42%) of the 38 patients with high risk polyps had adverse outcomes (p<0.001). Independent adverse risk factors were incomplete polypectomy and a resected margin not clearly cancer-free; all other risk factors were only associated with adverse outcome when in combination. As no patients with low risk malignant polyps had adverse outcomes, polypectomy alone seems sufficient for these cases. In the high risk group, surgery is recommended when either of the two independent risk factors, incomplete polypectomy or a resection margin not clearly cancer-free, is present or if there is a combination of other risk factors. As lymphatic or venous invasion or grade III cancer did not have an adverse outcome when the sole risk factor, operations in such cases should be individually assessed on the basis of surgical risk.

[Retroperitoneal liposarcoma as etiology of abdominal pain. Case report and literature review].

PubMed

Pérez-Ponce, Yisvanth; Castellanos-Alejandre, Raúl; Guerrero-Romero, J Francisco; Estrada-León, Felipe; Torres-Lobatón, Alfonso

2008-01-01

Soft tissue sarcomas are very uncommon types of tumors, with their embryological origin in the mesoderm and in nerve structures of the neuroectodermic layer. They represent only 1.5% of cases in the National Registry of Malignant Tumors in Mexico. They can be encountered anywhere connective soft tissue is found. Because of their specialized localization, retroperitoneal soft tissue sarcomas have a propensity to remain asymptomatic for long periods of time and reach a large size before being diagnosed. The only accepted treatment is wide surgical excision with clear margins, without a clear benefit for adjuvant treatment. The very uncommon nature of these tumors and their varied histopathology, site and behavior classify them as a difficult entity in terms of treatment. We present here the case of a 66-year-old female with a left-side retroperitoneal tumor, complaining only of vague abdominal pain as the presenting symptom. A CT-guided needle biopsy reported a sarcoma and the patient was subjected to laparatomy with complete resection of the tumor (30 x 13 x 10 cm). Histopathological report demonstrated a low-grade retroperitoneal sarcoma and free macroscopic and microscopic borders, without obvious invasion except for left kidney and ureter. The patient refused adjuvant treatment, and she is disease-free 7 years after treatment. Retroperitoneal sarcomas can cause pain and reach very large sizes. The best treatment available is wide surgical resection with clear margins. The most important prognostic factors are free margins, type of resection, age of patient and tumor histology.

Solo-Surgeon Single-Port Laparoscopic Anterior Resection for Sigmoid Colon Cancer: Comparative Study.

PubMed

Choi, Byung Jo; Jeong, Won Jun; Kim, Say-June; Lee, Sang Chul

2018-03-01

To report our experience with solo-surgeon, single-port laparoscopic anterior resection (solo SPAR) for sigmoid colon cancer. Data from sigmoid colon cancer patients who underwent anterior resections (ARs) using the single-port, solo surgery technique (n = 31) or the conventional single-port laparoscopic technique (n = 45), between January 2011 and July 2016, were retrospectively analyzed. In the solo surgeries, making the transumbilical incision into the peritoneal cavity was facilitated through the use of a self-retaining retractor system. After establishing a single port through the umbilicus, an adjustable mechanical camera holder replaced the human scope assistant. Patient and tumor characteristics and operative, pathologic, and postoperative outcomes were compared. The operative times and estimated blood losses were similar for the patients in both treatment groups. In addition, most of the postoperative variables were comparable between the two groups, including postoperative complications and hospital stays. In the solo SPAR group, comparable lymph nodes were attained, and sufficient proximal and distal cut margins were obtained. The difference in the proximal cut margin significantly favored the solo SPAR, compared with the conventional AR group (P = .000). This study shows that solo SPAR, using a passive camera system, is safe and feasible for use in sigmoid colon cancer surgery, if performed by an experienced laparoscopic surgeon. In addition to reducing the need for a surgical assistant, the oncologic requirements, including adequate margins and sufficient lymph node harvesting, could be fulfilled. Further evaluations, including prospective randomized studies, are warranted.

Liver resection for metastases of tracheal adenoid cystic carcinoma: Report of two cases.

PubMed

Hashimoto, Shintaro; Sumida, Yorihisa; Tobinaga, Shuichi; Wada, Hideo; Wakata, Kouki; Nonaka, Takashi; Kunizaki, Masaki; Hidaka, Shigekazu; Kinoshita, Naoe; Sawai, Terumitsu; Nagayasu, Takeshi

2018-05-16

Tracheal adenoid cystic carcinoma (ACC) is rare and accounts for <1% of all lung cancers. Although ACC is classified as a low-grade tumor, metastases are frequently identified in the late period. Extrapulmonary metastases are rare, and their resection has rarely been reported. Case 1: A 77-year-old man underwent tracheal resection for ACC with postoperative radiation (60 Gy) 14 years before　(at the age of 63). He underwent two subsequent pulmonary resections for metastases. Fourteen years after the first operation, he underwent extended right posterior segmentectomy with resection of segment IV and radiofrequency ablation for metastases of ACC to the liver. He was diagnosed with metastases to the kidney with peritoneal dissemination 4 years after the liver resection and died of pneumonia 2 years later. Case 2: A 53-year-old woman underwent a two-stage operation involving tracheal resection for ACC and partial resection of liver segments II and V for metastases of ACC to the liver. The tracheal margin was histopathologically positive. Postoperative radiation was performed, and she was tumor-free for 10 months after the liver resection. Complete resection of tracheal ACC provides better survival. Radiotherapy is also recommended. However, the optimal treatment for metastases of ACC is unclear, especially because liver resection for metastases of tracheal ACC is rarely reported. Our two cases of metastases of tracheal ACC were surgically managed with good outcomes. Liver resection for metastases of tracheal ACC may contribute to long survival. Copyright © 2018. Published by Elsevier Ltd.

Tissue preservation with mass spectroscopic analysis: Implications for cancer diagnostics.

PubMed

Hall, O Morgan; Peer, Cody J; Figg, William D

2018-05-17

Surgical intervention is a common treatment modality for localized cancer. Post-operative analysis involves evaluation of surgical margins to assess whether all malignant tissue has been resected because positive surgical margins lead to a greater likelihood of recurrence. Secondary treatments are utilized to minimize the negative effects of positive surgical margins. Recently, in Science Translational Medicine, Zhang et al describe a new mass spectroscopic technique that could potentially decrease the likelihood of positive surgical margins. Their nondestructive in vivo tissue sampling leads to a highly accurate and rapid cancer diagnosis with great precision between healthy and malignant tissue. This new tool has the potential to improve surgical margins and accelerate cancer diagnostics by analyzing biomolecular signatures of various tissues and diseases.

Theory underlying CRM training: Psychological issues in flight crew performance and crew coordination

NASA Technical Reports Server (NTRS)

Helmreich, Robert L.

1987-01-01

What psychological theory and research can reveal about training in Cockpit Resource Management (CRM) is summarized. A framework is provided for the critical analysis of current approaches to CRM training. Background factors and definitions critical to evaluating CRM are reviewed, followed by a discussion of issues directly related to CRM training effectiveness. Some of the things not known about the optimization of crew performance and the research needed to make these efforts as effective as possible are described.

Early Oral Tongue Squamous Cell Carcinoma: Sampling of Margins From Tumor Bed and Worse Local Control.

PubMed

Maxwell, Jessica H; Thompson, Lester D R; Brandwein-Gensler, Margaret S; Weiss, Bernhard G; Canis, Martin; Purgina, Bibianna; Prabhu, Arpan V; Lai, Chi; Shuai, Yongli; Carroll, William R; Morlandt, Anthony; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T; Ferris, Robert L; Seethala, Raja; Chiosea, Simion I

2015-12-01

Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique. To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC. A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pN0 oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015. In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR. Local recurrence. Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P < .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin. The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen-based margin assessment is recommended.

Early Oral Tongue Squamous Cell Carcinoma Sampling of Margins From Tumor Bed and Worse Local Control

PubMed Central

Maxwell, Jessica H.; Thompson, Lester D. R.; Brandwein-Gensler, Margaret S.; Weiss, Bernhard G.; Canis, Martin; Purgina, Bibianna; Prabhu, Arpan V.; Lai, Chi; Shuai, Yongli; Carroll, William R.; Morlandt, Anthony; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T.; Ferris, Robert L.; Seethala, Raja; Chiosea, Simion I.

2017-01-01

IMPORTANCE Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique. OBJECTIVE To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC. DESIGN, SETTING, AND PARTICIPANTS A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pN0 oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015. INTERVENTIONS In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR. MAIN OUTCOMES AND MEASURES Local recurrence. RESULTS Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P < .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin. CONCLUSIONS AND RELEVANCE The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen–based margin assessment is recommended. PMID:26225798

CO2 laser versus cold steel margin analysis following endoscopic excision of glottic cancer

PubMed Central

2014-01-01

Objective To compare the suitability of CO2 laser with steel instruments for margin excision in transoral laser microsurgery. Methods Prospective randomized blinded study. Patients with glottic cancer undergoing laser resection were randomized to margin excision by either steel instruments or CO2 laser. Margins were analyzed for size, interpretability and degree of artifact by a pathologist who was blinded to technique. Results 45 patients were enrolled in the study with 226 total margins taken. 39 margins taken by laser had marked artifact and 0 were uninterpretable. 20 margins taken by steel instruments had marked artifact, and 2 were uninterpretable. Controlling for margin size, the laser technique was associated with increasing degrees of margin artifact (p = 0.210), but there was no difference in crude rates of uninterpretability (p = 0.24). Conclusion Laser margin excision is associated with a greater degree of artifact than steel instrument excision, but was not associated with higher rate of uninterpretability. PMID:24502856

Evaluation of moisture damage in asphalt concrete with CRM motorcycle tire waste passing #50 sieve size

NASA Astrophysics Data System (ADS)

Siswanto, Henri; Supriyanto, Bambang; Pranoto, Pranoto; Chandra, Pria Rizky; Hakim, Arief Rahman

2017-09-01

The objective of this experimental research is to evaluate moisture damage in Asphalt Concrete (AC) with Crumb Rubber Modified (CRM) motorcycle tire waste passing #50 and retaining #100 sieve size. Two gradations were used in this research, the first gradation is usual for asphalt concrete base (ACB) and the second gradation is for asphalt concrete wearing course (ACWC). Marshall testing apparatus was used for testing the Marshall specimens. Seven levels of CRM content were used, namely 0%, 0.5%, 1%, 1.5%, 3%, 4.5% and 6% by weight of mixtures. Retained stability represent the level of moisture damage of AC pavement. The result indicates that addition CRM to the AC mixture increases their the stability to a maximum value and subsequent addition decrease the stability. The addition CRM to AC decreases their moisture damage susceptibility. AC with 1% CRM is the best asphalt-CRM mix.

The ontology model of FrontCRM framework

NASA Astrophysics Data System (ADS)

Budiardjo, Eko K.; Perdana, Wira; Franshisca, Felicia

2013-03-01

Adoption and implementation of Customer Relationship Management (CRM) is not merely a technological installation, but the emphasis is more on the application of customer-centric philosophy and culture as a whole. CRM must begin at the level of business strategy, the only level that thorough organizational changes are possible to be done. Changes agenda can be directed to each departmental plans, and supported by information technology. Work processes related to CRM concept include marketing, sales, and services. FrontCRM is developed as framework to guide in identifying business processes related to CRM in which based on the concept of strategic planning approach. This leads to processes and practices identification in every process area related to marketing, sales, and services. The Ontology model presented on this paper by means serves as tools to avoid framework misunderstanding, to define practices systematically within process area and to find CRM software features related to those practices.

Structural determinants of nuclear export signal orientation in binding to exportin CRM1

DOE PAGES

Fung, Ho Yee Joyce; Fu, Szu -Chin; Brautigam, Chad A.; ...

2015-09-08

The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). A comparison of minus and plus NESs identified structural and sequencemore » determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.« less

An observational analysis of surgical team compliance with perioperative safety practices after crew resource management training.

PubMed

France, Daniel J; Leming-Lee, Susie; Jackson, Tom; Feistritzer, Nancye R; Higgins, Michael S

2008-04-01

Acknowledging the need to improve team communication and coordination among health care providers, health care administrators and improvement officers have been quick to endorse and invest in aviation crew resource management (CRM). Despite the increased interest in CRM there exists limited data on the effectiveness of CRM to change team behavior and performance in clinical settings. Direct observational analyses were performed on 30 surgical teams (15 neurosurgery cases and 15 cardiac cases) to evaluate surgical team compliance with integrated safety and CRM practices after extensive CRM training. Observed surgical teams were compliant with only 60% of the CRM and perioperative safety practices emphasized in the training program. The results highlight many of the challenges the health care industry faces in its efforts to adapt CRM from aviation to medicine. Additional research is needed to develop and test new team training methods and performance feedback mechanisms for clinical teams.

CRM Implementation in Nonprofits: An Analysis of the Success Factors

ERIC Educational Resources Information Center

Grattan, Kelly E.

2012-01-01

Constituent Relationship Management ("CRM") is defined as an organization-wide strategy designed to enable the organization to better manage, track and steward its constituents. CRM has benefited for-profit enterprises for nearly three decades. In the nonprofit sector, the concept of CRM is fairly new. Despite the increase in CRM…

Hospital CRM: unexplored frontier of revenue growth?

PubMed

Young, Thomas

2007-10-01

Customer relationship management (CRM) has a less-than-stellar reputation, in large part because efforts to implement it have been piecemeal and not well funded. The technologies now exist to make CRM much more effective than it has been in the past. Many hospitals today are demonstrating a substantial ROI from implementing a comprehensive CRM program.

Differences in serum thyroglobulin measurements by 3 commercial immunoradiometric assay kits and laboratory standardization using Certified Reference Material 457 (CRM-457).

PubMed

Lee, Ji In; Kim, Ji Young; Choi, Joon Young; Kim, Hee Kyung; Jang, Hye Won; Hur, Kyu Yeon; Kim, Jae Hyeon; Kim, Kwang-Won; Chung, Jae Hoon; Kim, Sun Wook

2010-09-01

Serum thyroglobulin (Tg) is essential in the follow-up of patients with differentiated thyroid carcinoma (DTC). However, interchangeability and standardization between Tg assays have not yet been achieved, even with the development of an international Tg standard (Certified Reference Material 457 [CRM-457]). Serum Tg from 30 DTC patients and serially diluted CRM-457 were measured using 3 different immunoradiometric assays (IRMA-1, IRMA-2, IRMA-3). The intraclass correlation coefficient (ICC) method was used to describe the concordance of each IRMA to CRM-457. The serum Tg measured by 3 different IRMAs correlated well (r > .85, p < .0001), but clinically relevant discrepancies were found in 13.3% of patients. IRMA-3, which claims to be standardized to CRM-457, showed the best ICC (p(1) = .98) for the CRM-457. Hospitals caring for patients with DTC should either set their own cutoffs for IRMAs for Tg based on their patient pools, or adopt IRMAs standardized to CRM-457 and calibrate their laboratory using CRM-457.

The Randomized CRM: An Approach to Overcoming the Long-Memory Property of the CRM

PubMed Central

Koopmeiners, Joseph S.; Wey, Andrew

2017-01-01

The primary object of a phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent subjects are treated at progressively higher dose levels until the MTD is identified. The continual reassessment method (CRM) is a popular model-based dose-escalation design, which utilizes a formal model for the relationship between dose and toxicity to guide dose-finding. Recently, it was shown that the CRM has a tendency to get “stuck” on a dose-level, with little escalation or de-escalation in the late stages of the trial, due to the long-memory property of the CRM. We propose the randomized CRM (rCRM), which introduces random escalation and de-escalation into the standard CRM dose-finding algorithm, as well as a hybrid approach that incorporates escalation and de-escalation only when certain criteria are met. Our simulation results show that both the rCRM and the hybrid approach reduce the trial-to-trial variability in the number of cohorts treated at the MTD but that the hybrid approach has a more favorable trade-off with respect to the average number treated at the MTD. PMID:28340333

The Randomized CRM: An Approach to Overcoming the Long-Memory Property of the CRM.

PubMed

Koopmeiners, Joseph S; Wey, Andrew

2017-01-01

The primary object of a Phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent subjects are treated at progressively higher dose levels until the MTD is identified. The continual reassessment method (CRM) is a popular model-based dose-escalation design, which utilizes a formal model for the relationship between dose and toxicity to guide dose finding. Recently, it was shown that the CRM has a tendency to get "stuck" on a dose level, with little escalation or de-escalation in the late stages of the trial, due to the long-memory property of the CRM. We propose the randomized CRM (rCRM), which introduces random escalation and de-escalation into the standard CRM dose-finding algorithm, as well as a hybrid approach that incorporates escalation and de-escalation only when certain criteria are met. Our simulation results show that both the rCRM and the hybrid approach reduce the trial-to-trial variability in the number of cohorts treated at the MTD but that the hybrid approach has a more favorable tradeoff with respect to the average number treated at the MTD.

[Does a sector resection of the breast cure nodal mastopathy?].

PubMed

Li, L A; Martyniuk, V V

1998-01-01

Results of the clinico-morphological investigation of 265 patients with localized mastopathy who were submitted to sectorial resection showed that in the margins of the operative wound there were morphological signs of mastopathy in 252 (95.1%) patients. The results obtained confirm the opinion that structural alterations of the tissues known to be the essential feature of fibroadenomatosis can not be local, they are of diffuse character. So, the sectorial resection performed for localized mastopathy can not be radical and is of no therapeutic significance. The indication to surgical intervention must be determined not so much by the necessary treatment as by the real risk of hypo-diagnosis of breast cancer. So, there is no need to fulfil the sectorial resection for localized mastopathy. It is enough to make operation of less volume (excision biopsy).

[A Case of Curatively Resected Locally Advanced Cancer of the Pancreatic Body Treated by Distal Pancreatectomy with En Bloc Celiac Axis Resection after Preoperative Intensive Treatment].

PubMed

Kim, Yongkook; Hoshino, Hiromitsu; Kakita, Naruyasu; Yamasaki, Masaru; Hosoda, Yohei; Nishino, Masaya; Okano, Miho; Kawada, Junji; Okuyama, Masaki; Tsujinaka, Toshimasa

2016-11-01

A 70-year-old woman with locally advanced pancreatic body cancer invading the celiac axis underwent 4 courses of preoperative chemotherapy consisting of gemcitabine(GEM)plus nab-paclitaxel(nab-PTX)on days 1, 8, and 15 every 4 weeks, followed by radiation therapy(CRT; 50.4Gy delivered in 28 daily fractions). The tumor size was greatly diminished and levels of all tumor markers were decreased. R0resection by distal pancreatectomy with en bloc celiac axis resection(DP-CAR)was performed. The histopathologic findings showed that the effect of CRT was grade 2b(Evans' classification), and the surgical margins were histologically clear. After the surgery, S-1 was administered continuously. The patient shows no signs of recurrence 1 year after surgery.

Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains.

PubMed

Keren, Ido; Klipcan, Liron; Bezawork-Geleta, Ayenachew; Kolton, Max; Shaya, Felix; Ostersetzer-Biran, Oren

2008-08-22

CRM (chloroplast RNA splicing and ribosome maturation) is a recently recognized RNA-binding domain of ancient origin that has been retained in eukaryotic genomes only within the plant lineage. Whereas in bacteria CRM domains exist as single domain proteins involved in ribosome maturation, in plants they are found in a family of proteins that contain between one and four repeats. Several members of this family with multiple CRM domains have been shown to be required for the splicing of specific plastidic group II introns. Detailed biochemical analysis of one of these factors in maize, CRS1, demonstrated its high affinity and specific binding to the single group II intron whose splicing it facilitates, the plastid-encoded atpF intron RNA. Through its association with two intronic regions, CRS1 guides the folding of atpF intron RNA into its predicted "catalytically active" form. To understand how multiple CRM domains cooperate to achieve high affinity sequence-specific binding to RNA, we analyzed the RNA binding affinity and specificity associated with each individual CRM domain in CRS1; whereas CRM3 bound tightly to the RNA, CRM1 associated specifically with a unique region found within atpF intron domain I. CRM2, which demonstrated only low binding affinity, also seems to form specific interactions with regions localized to domains I, III, and IV. We further show that CRM domains share structural similarities and RNA binding characteristics with the well known RNA recognition motif domain.

The German clinical risk management survey for hospitals: Implementation levels and areas for improvement in 2015.

PubMed

Manser, Tanja; Frings, Janina; Heuser, Gregory; Mc Dermott, Fiona

2016-01-01

Despite the growing recognition of the need to implement systematic approaches for managing the risks associated with healthcare, few studies have investigated the level of implementation for clinical risk management (CRM) at a national level. Therefore, this study aimed to assess the current level of CRM implementation in German hospitals and to explore differences across hospital types. From March to June 2015, persons responsible for CRM in 2,617 hospitals and rehabilitation clinics in Germany were invited to participate in a voluntary online survey assessing the level of implementation for various aspects of CRM: CRM strategy, structures and processes; risk assessment (risk identification, risk analysis, risk evaluation) with a focus on incident reporting systems; risk mitigation measures; and risk monitoring and reporting. 572 hospitals participated in the survey (response rate 22 %). Most of these hospitals had a formalised, binding CRM strategy (72 %). 66 % had a centralised and 34 % a decentralised CRM structure. We also found that, despite a broad range of risk assessment methods being applied, there was a lack of integration of risk information from different data sources. Hospitals also reported a high level of implementation of critical incident reporting systems with a strong preference for local (74 %) over transorganisational systems. This study provides relevant data to inform targeted interventions concerning CRM implementation at a national level and to consider the specific context of different types of hospitals more carefully in this process. The approach to CRM assessment illustrated in this article could be the basis of a system for monitoring CRM over time and, thus, for evaluating the impact of strategy decisions at the policy level on CRM development. Copyright © 2016. Published by Elsevier GmbH.

NBL CRM 112-A: A new certified isotopic composition

NASA Astrophysics Data System (ADS)

Thomas, R. B.; Essex, R. M.; Mason, P.

2007-12-01

NBL CRM 112-A Uranium Metal Assay Standard is commonly used as a natural uranium isotopic reference material within the earth science mass spectrometry community. The metal is from the same parent material as NBS SRM 960, the uranyl nitrate solution, CRM 145, and the high-purity uranyl nitrate solution CRM 145-B. Because CRM 112-A has not yet been certified for isotopic composition, it has been assumed that this material has a natural 235U/238U (0.0072527), and the δ234U has been determined by measurement (e.g. -37.1‰; Cheng et al., 2000). These values have been widely used to calibrate the concentration of spikes and standards, and to correct measurements for instrument or mass bias. New, preliminary, isotopic measurements on CRM 145 and CRM 112-A performed at New Brunswick Laboratory suggest that these reference materials have a slightly lower 235U/238U and δ234U than have been commonly used. If this is the case, then data using the accepted values may be slightly biased. The significance of this bias will depend on the uncertainty of the measurement, how the CRM 112-A data is used to correct measurement data, the cited values that were used to correct the data, and the final certified values of the CRM. This fall, New Brunswick Laboratory is certifying the isotopic composition of the CRM 112-A metal using high precision thermal ionization mass spectrometry techniques. Upon completion of certification, the new CRM 112- A standard with certified isotopic ratios will provide the earth science community with a well characterized and traceable reference for calibrating and correcting their mass spectrometry measurement systems.

A comparison of global rating scale and checklist scores in the validation of an evaluation tool to assess performance in the resuscitation of critically ill patients during simulated emergencies (abbreviated as "CRM simulator study IB").

PubMed

Kim, John; Neilipovitz, David; Cardinal, Pierre; Chiu, Michelle

2009-01-01

Crisis resource management (CRM) skills are a set of nonmedical skills required to manage medical emergencies. There is currently no gold standard for evaluation of CRM performance. A prior study examined the use of a global rating scale (GRS) to evaluate CRM performance. This current study compared the use of a GRS and a checklist as formal rating instruments to evaluate CRM performance during simulated emergencies. First-year and third-year residents participated in two simulator scenarios each. Three raters then evaluated resident performance in CRM using edited video recordings using both a GRS and a checklist. The Ottawa GRS provides a seven-point anchored ordinal scale for performance in five categories of CRM, and an overall performance score. The Ottawa CRM checklist provides 12 items in the five categories of CRM, with a maximum cumulative score of 30 points. Construct validity was measured on the basis of content validity, response process, internal structure, and response to other variables. T-test analysis of Ottawa GRS scores was conducted to examine response to the variable of level of training. Intraclass correlation coefficient (ICC) scores were used to measure inter-rater reliability for both scenarios. Thirty-two first-year and 28 third-year residents participated in the study. Third-year residents produced higher mean scores for overall CRM performance than first-year residents (P < 0.05), and in all individual categories within the Ottawa GRS (P < 0.05) and the Ottawa CRM checklist (P < 0.05). This difference was noted for both scenarios and for each individual rater (P < 0.05). No statistically significant difference in resident scores was observed between scenarios for both instruments. ICC scores of 0.59 and 0.61 were obtained for Scenarios 1 and 2 with the Ottawa GRS, whereas ICC scores of 0.63 and 0.55 were obtained with the Ottawa CRM checklist. Users indicated a strong preference for the Ottawa GRS given ease of scoring, presence of an overall score, and the potential for formative evaluation. Construct validity seems to be present when using both the Ottawa GRS and CRM checklist to evaluate CRM performance during simulated emergencies. Data also indicate the presence of moderate inter-rater reliability when using both the Ottawa GRS and CRM checklist.

Cooperativity among Rev-Associated Nuclear Export Signals Regulates HIV-1 Gene Expression and Is a Determinant of Virus Species Tropism

PubMed Central

Aligeti, Mounavya; Behrens, Ryan T.; Pocock, Ginger M.; Schindelin, Johannes; Dietz, Christian; Eliceiri, Kevin W.; Swanson, Chad M.; Malim, Michael H.; Ahlquist, Paul

2014-01-01

ABSTRACT Murine cells exhibit a profound block to HIV-1 virion production that was recently mapped to a species-specific structural attribute of the murine version of the chromosomal region maintenance 1 (mCRM1) nuclear export receptor and rescued by the expression of human CRM1 (hCRM1). In human cells, the HIV-1 Rev protein recruits hCRM1 to intron-containing viral mRNAs encoding the Rev response element (RRE), thereby facilitating viral late gene expression. Here we exploited murine 3T3 fibroblasts as a gain-of-function system to study hCRM1's species-specific role in regulating Rev's effector functions. We show that Rev is rapidly exported from the nucleus by mCRM1 despite only weak contributions to HIV-1's posttranscriptional stages. Indeed, Rev preferentially accumulates in the cytoplasm of murine 3T3 cells with or without hCRM1 expression, in contrast to human HeLa cells, where Rev exhibits striking en masse transitions between the nuclear and cytoplasmic compartments. Efforts to bias Rev's trafficking either into or out of the nucleus revealed that Rev encoding a second CRM1 binding domain (Rev-2xNES) or Rev-dependent viral gag-pol mRNAs bearing tandem RREs (GP-2xRRE), rescue virus particle production in murine cells even in the absence of hCRM1. Combined, these results suggest a model wherein Rev-associated nuclear export signals cooperate to regulate the number or quality of CRM1's interactions with viral Rev/RRE ribonucleoprotein complexes in the nucleus. This mechanism regulates CRM1-dependent viral gene expression and is a determinant of HIV-1's capacity to produce virions in nonhuman cell types. IMPORTANCE Cells derived from mice and other nonhuman species exhibit profound blocks to HIV-1 replication. Here we elucidate a block to HIV-1 gene expression attributable to the murine version of the CRM1 (mCRM1) nuclear export receptor. In human cells, hCRM1 regulates the nuclear export of viral intron-containing mRNAs through the activity of the viral Rev adapter protein that forms a multimeric complex on these mRNAs prior to recruiting hCRM1. We demonstrate that Rev-dependent gene expression is poor in murine cells despite the finding that, surprisingly, the bulk of Rev interacts efficiently with mCRM1 and is rapidly exported from the nucleus. Instead, we map the mCRM1 defect to the apparent inability of this factor to engage Rev multimers in the context of large viral Rev/RNA ribonucleoprotein complexes. These findings shed new light on HIV-1 gene regulation and could inform the development of novel antiviral strategies that target viral gene expression. PMID:25275125

[NOTES ASSISTED ENDOLUMENAL RECTAL RESECTION AND SPECIMEN EXTRACTION WITHOUT RECTAL STUMP OPENING - OUR EXPERIENCE WITH THIS NOVEL TECHNIQUE IN A PORCINE MODEL].

PubMed

Kvasha, Anton; Rosenthal, Eyal; Khalifa, Muhammad; Waksman, Igor

2017-05-01

Laparoscopic surgery has long been used for colon and rectal resection, and the laparoscopic-assisted approach has prevailed in surgical practice. While this technique includes the fashioning of an intra-corporeal anastomosis, it still requires an abdominal incision for specimen extraction. Elimination of the abdominal incision and its potential complications has been the motivation for the development of natural orifice specimen extraction (NOSE) techniques. Many of these techniques make use of an open rectal stump, which poses as a potential for intra-abdominal contamination. Our group has recently described a novel, NOTES assisted, clean, endoluminal rectal resection utilizing transabdominal and transanal approaches. In this paper we report the combined experience of two study groups: an open approach to the abdominal cavity and a laparoscopic approach to the peritoneal cavity. Ten female pigs were used for this research; 5 in a group using an open approach and 5 using a laparoscopic approach for the abdominal part of the procedure. During the procedure, the rectum was mobilized. An end-to-end circular stapler was used to create a recto-rectal intussusception and pull-through (IPT). The specimen was resected and extracted by making a full thickness incision through 2 bowel walls. The stapler was applied, and a recto-rectal anastomosis created. This was allowed to retract into the abdomen. Peritoneal fluid was sampled for bacteria, the pigs were sacrificed immediately after the experiment and necropsy was performed. All 10 pigs underwent an endoluminal rectal resection utilizing the trans-anal IPT technique. The proximal and distal resection margins remained approximated over the shaft of the anvil after bowel resection in all 10 subjects. A 2- to 4-mm resection margin, distal to the ligatures was accomplished consistently in all 10 subjects. No aerobic or anaerobic bacterial growth was observed in any of the peritoneal fluid samples. Our research demonstrated the feasibility of the described technique in both open and laparoscopic approaches to a clean endoluminal bowel resection and trans-anal specimen extraction without rectal stump opening. The fact that no bacterial growth was found in any of the peritoneal samples supports the initial classification of this novel technique as clean, as opposed to clean contaminated, which classifies all other techniques in use to date.

Microsurgical resection of intramedullary spinal cord ependymoma.

PubMed

McCormick, Paul C

2014-09-01

Ependymomas are the most commonly occurring intramedullary spinal cord tumor in adults. With few exceptions these tumors are histologically benign, although they exhibit some biologic variability with respect to growth rate. While unencapsulated, spinal ependymomas are non-infiltrative and present a clear margin of demarcation from the surrounding spinal cord that serves as an effective dissection plane. This video demonstrates the technique of microsurgical resection of an intramedullary ependymoma through a posterior midline myelotomy. The video can be found here: http://youtu.be/lcHhymSvSqU.

Session 3: Beyond the boundaries of Total Mesorectal Excision - where surgeons fear to tread.

PubMed

Patel, A; Holm, T; Wale, A; Rutten, H; Nicholls, J; Hawkins, M; Steele, R J C; Marks, J; Brown, G

2018-05-01

Approximately 10-15% of patients present with an advanced rectal cancer that extends beyond the conventional total mesorectal excision (TME) planes. In such cases extending the surgery to ensure resection with clear margins (R0 resection) is essential in order to achieve long-term cure. Professor Holm describes the techniques of beyond-TME exenterative surgery, the methods of patient selection and outcomes. Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.

Total humerus replacement for osteosarcoma with proximal part of humerus: a case report

PubMed Central

2012-01-01

Incisional biopsy and intramedullary pinning were performed for pathological fracture associated with a malignant bone tumor of the proximal humerus. Osteosarcoma, for which preoperative chemotherapy had been performed, was confirmed by postoperative pathological examination. To achieve wide resection and acquire a safe resected margin, total humerus replacement was performed, and the whole humerus was reconstructed using the Howmedica Modular Reconstruction system. The patient resumed normal activities, although mild contracture of the elbow joint remains 8 years after surgery. PMID:22333118

The evolution of Crew Resource Management training in commercial aviation

NASA Technical Reports Server (NTRS)

Helmreich, R. L.; Merritt, A. C.; Wilhelm, J. A.

1999-01-01

In this study, we describe changes in the nature of Crew Resource Management (CRM) training in commercial aviation, including its shift from cockpit to crew resource management. Validation of the impact of CRM is discussed. Limitations of CRM, including lack of cross-cultural generality are considered. An overarching framework that stresses error management to increase acceptance of CRM concepts is presented. The error management approach defines behavioral strategies taught in CRM as error countermeasures that are employed to avoid error, to trap errors committed, and to mitigate the consequences of error.

Determination of the amino acid change responsible for the nontoxic, cross-reactive exotoxin A protein (CRM 66) of Pseudomonas aeruginosa PAO-PR1.

PubMed Central

Wick, M J; Iglewski, B H

1988-01-01

Analysis of purified exotoxin A from parental Pseudomonas aeruginosa PAO1 and mutant strain PAO-PR1, which produces enzymatically inactive exotoxin A (CRM 66), revealed that CRM 66 lost 90% of parental enzymatic activity. Nucleotide sequence analysis of cloned exotoxin A genes showed a single amino acid substitution in CRM 66. Position 426 in the mature protein of parental (PAO1) exotoxin A is histidine, whereas in CRM 66, it is tyrosine. Images PMID:3141388

Biopsy forceps is inadequate for the resection of diminutive polyps.

PubMed

Efthymiou, M; Taylor, A C; Desmond, P V; Allen, P B; Chen, R Y

2011-04-01

Cold biopsy forceps polypectomy (CBP) is often used for the removal of diminutive polyps. The efficacy of the technique has not been thoroughly assessed. The aim of this study was to prospectively assess the efficacy of CBP for removing diminutive polyps. This was a prospective study from St Vincent's Hospital, a tertiary referral hospital in Melbourne, Australia. A total of 143 patients were screened and 52 patients with ≥ 1 diminutive polyps were enrolled. CBP was used to resect diminutive polyps until no polyp tissue was visible. The polyp base was then resected using endoscopic mucosal resection (EMR) with a 1 - 2-mm margin. The CBP and EMR samples were compared to assess completeness of the resection. Overall 39 % (21 / 54) of diminutive polyps were completely resected using CBP. After binary logistic regression analysis, polyp histology was found to be predictive of resection, with complete resection of 62 % (13 / 21) for adenomas and 24 % (8 / 33) for hyperplastic polyps (odds ratio 5.1; P = 0.008). The size and number of bites taken with the forceps were not predictive of complete response. Within the limitations of a modest sample size, CBP appears to be inadequate treatment for the removal of diminutive polyps. © Georg Thieme Verlag KG Stuttgart · New York.

Evaluating Surgical Margins with Optical Spectroscopy and Spectral Imaging Following Breast Cancer Resection

DTIC Science & Technology

2009-08-01

Raman spectral features of hydroxyapatite crystals (found in breast calcifications) through overlying lean chicken breast tissue [18]. Thus, the...form o f spectral imaging to examine entire margins in a single acquisition . 23 1. INTRODUCTION Of the approxim ately 180,000 patien ts each...ination sources into a single, 10-mm-core liquid light guide, which delivered the illumination light to the sample. 2.3 Data acquisition For lum

Frozen section analysis of margins for head and neck tumor resections: reduction of sampling errors with a third histologic level.

PubMed

Olson, Stephen M; Hussaini, Mohammad; Lewis, James S

2011-05-01

Frozen section analysis is an essential tool for assessing margins intra-operatively to assure complete resection. Many institutions evaluate surgical defect edge tissue provided by the surgeon after the main lesion has been removed. With the increasing use of transoral laser microsurgery, this method is becoming even more prevalent. We sought to evaluate error rates at our large academic institution and to see if sampling errors could be reduced by the simple method change of taking an additional third section on these specimens. All head and neck tumor resection cases from January 2005 through August 2008 with margins evaluated by frozen section were identified by database search. These cases were analyzed by cutting two levels during frozen section and a third permanent section later. All resection cases from August 2008 through July 2009 were identified as well. These were analyzed by cutting three levels during frozen section (the third a 'much deeper' level) and a fourth permanent section later. Error rates for both of these periods were determined. Errors were separated into sampling and interpretation types. There were 4976 total frozen section specimens from 848 patients. The overall error rate was 2.4% for all frozen sections where just two levels were evaluated and was 2.5% when three levels were evaluated (P=0.67). The sampling error rate was 1.6% for two-level sectioning and 1.2% for three-level sectioning (P=0.42). However, when considering only the frozen section cases where tumor was ultimately identified (either at the time of frozen section or on permanent sections) the sampling error rate for two-level sectioning was 15.3 versus 7.4% for three-level sectioning. This difference was statistically significant (P=0.006). Cutting a single additional 'deeper' level at the time of frozen section identifies more tumor-bearing specimens and may reduce the number of sampling errors.

Contralateral posterior interhemispheric approach to deep medial parietooccipital vascular malformations: surgical technique and results.

PubMed

Burkhardt, Jan-Karl; Winkler, Ethan A; Lawton, Michael T

2017-07-21

OBJECTIVE Deep medial parietooccipital arteriovenous malformations (AVMs) and cerebral cavernous malformations (CCMs) are traditionally resected through an ipsilateral posterior interhemispheric approach (IPIA), which creates a deep, perpendicular perspective with limited access to the lateral margins of the lesion. The contralateral posterior interhemispheric approach (CPIA) flips the positioning, with the midline positioned horizontally for retraction due to gravity, but with the AVM on the upper side and the approach from the contralateral, lower side. The aim of this paper was to analyze whether the perpendicular angle of attack that is used in IPIA would convert to a parallel angle of attack with the CPIA, with less retraction, improved working angles, and no significant increase in risk. METHODS A retrospective review of pre- and postoperative clinical and radiographic data was performed in 8 patients who underwent a CPIA. RESULTS Three AVMs and 5 CCMs were resected using the CPIA, with an average nidus size of 2.3 cm and CCM diameter of 1.7 cm. All lesions were resected completely, as confirmed on postoperative catheter angiography or MRI. All patients had good neurological outcomes, with either stable or improved modified Rankin Scale scores at last follow-up. CONCLUSIONS The CPIA is a safe alternative approach to the IPIA for deep medial parietooccipital vascular malformations that extend 2 cm or more off the midline. Contralaterality and retraction due to gravity optimize the interhemispheric corridor, the surgical trajectory to the lesion, and the visualization of the lateral margin, without resection or retraction of adjacent normal cortex. Although the falx is a physical barrier to accessing the lesion, it stabilizes the ipsilateral hemisphere while gravity delivers the dissected lesion through the transfalcine window. Patient positioning, CSF drainage, venous preservation, and meticulous dissection of the deep margins are critical to the safety of this approach.

[Results of surgical treatment in ampullary and pancreatic carcinoma and its prognostic parameters after R0-resection].

PubMed

Ridwelski, K; Meyer, F; Schmidt, U; Lippert, H

2005-08-01

Resection is currently the only established reasonable therapeutic option with curative potential in pancreatic and ampullary carcinoma. The aim of the study was i) to analyze value and results of surgical therapy and ii) to detect the prognostic parameters, which determine significantly higher survival rates. Two-hundred-twenty patients with pancreatic and ampullary carcinoma (mean age, 61.4 years; 104 females/116 males) underwent surgery. Histologic investigation revealed 19 carcinomas of the papilla of Vater and 201 ductal pancreatic carcinomas. In 126 patients, stage IV a or b tumors were found, in addition, stage I (n =26), II (n = 17) and III (n = 51). Survival-rate was determined according to the method by Kaplan/Meier. Survival was compared using log-rank test. Association of several or multiple parameters with survival was tested using Cox model. Hundred-ten patients underwent tumor resection with primary curative intention (50 %): 96 resections of the pancreatic head, 2 total pancreatectomies and 12 left resections of the pancreas. R0-resection was achieved in 94 patients (42.7 %), whereas intervention was classified R1 in 10 and R2 in 6 cases. In addition, 60 palliative interventions (28 gastroenterostomies, 17 biliodigestive anastomoses, 15 anastomoses at both sites) and 50 explorative laparotomies were performed. In 42.3 % of patients, postoperative complications were found, but only 12/220 individuals died (overall letality, 5.4 %). Postoperative letality of curative pancreatic resections was 3.6 % (palliative intervention, 6.7 %; explorative laparotomy, 8.8 %). Five-year survival-rate of carcinoma of the papilla of Vater and pancreatic carcinoma was 73.3 % and 16.2 %, respectively (median survival time was 66.0 and 14.0 months, respectively). Taken together all other interventions, median survival time ranged between 4.0 (palliative intervention) to 10.0 months (R1-resection). No patient survived 5 years. Therefore, the most relevant prognostic factor was R0-resection. In addition, prognosis after successful R0-resection is determined significantly by tumor site, stage of the tumor (according to UICC), T- and N-category. Resection of pancreatic and ampullary carcinoma according to oncological criteria with tumor-free margins can be considered a treatment option with curative intention and potential. Despite relative high postoperative morbidity, only a low mortality rate was observed. The 5-year survival-rate of 16.2 % in ductal pancreatic carcinoma underlines the demand for the development of effective multimodal therapeutic concepts. Interventions with primary palliative intention or resections with microscopically or macroscopically detectable tumor residual in situ lead to no significant or only marginal prolongation of survival time. Such interventions in patients with pancreatic carcinoma are no reasonable treatment alternative. They are of value only for treatment of tumor-associated complications and problems.

Clinical risk management in mental health: a qualitative study of main risks and related organizational management practices.

PubMed

Briner, Matthias; Manser, Tanja

2013-02-04

A scientific understanding of clinical risk management (CRM) in mental health care is essential for building safer health systems and for improving patient safety. While evidence on patient safety and CRM in physical health care has increased, there is limited research on these issues in mental health care. This qualitative study provides an overview of the most important clinical risks in mental health and related organizational management practices. We conducted in-depth expert interviews with professionals responsible for CRM in psychiatric hospitals. Interviews were transcribed and analyzed applying qualitative content analysis to thematically sort the identified risks. The main concerns for CRM in mental health are a) violence and self-destructive behavior (i.e. protecting patients and staff from other patients, and patients from themselves), b) treatment errors, especially in the process of therapy, and c) risks associated with mental illnesses (e.g. psychosis or depression). This study identified critical differences to CRM in hospitals for physical disorder and challenges specific to CRM in mental health. Firstly, many psychiatric patients do not believe that they are ill and are therefore in hospital against their will. Secondly, staff safety is a much more prominent theme for CRM in mental health care as it is directly related to the specifics of mental illnesses. The current study contributes to the understanding of patient safety and raises awareness for CRM in mental health. The mental health specific overview of central risks and related organizational management practices offers a valuable basis for CRM development in mental health and an addition to CRM in general.

Centromeric retrotransposon lineages predate the maize/rice divergence and differ in abundance and activity.

PubMed

Sharma, Anupma; Presting, Gernot G

2008-02-01

Centromeric retrotransposons (CR) are located almost exclusively at the centromeres of plant chromosomes. Analysis of the emerging Zea mays inbred B73 genome sequence revealed two novel subfamilies of CR elements of maize (CRM), bringing the total number of known CRM subfamilies to four. Orthologous subfamilies of each of these CRM subfamilies were discovered in the rice lineage, and the orthologous relationships were demonstrated with extensive phylogenetic analyses. The much higher number of CRs in maize versus Oryza sativa is due primarily to the recent expansion of the CRM1 subfamily in maize. At least one incomplete copy of a CRM1 homolog was found in O. sativa ssp. indica and O. officinalis, but no member of this subfamily could be detected in the finished O. sativa ssp. japonica genome, implying loss of this prolific subfamily in that subspecies. CRM2 and CRM3, as well as the corresponding rice subfamilies, have been recently active but are present in low numbers. CRM3 is a full-length element related to the non-autonomous CentA, which is the first described CRM. The oldest subfamily (CRM4), as well as its rice counterpart, appears to contain only inactive members that are not located in currently active centromeres. The abundance of active CR elements is correlated with chromosome size in the three plant genomes for which high quality genomic sequence is available, and the emerging picture of CR elements is one in which different subfamilies are active at different evolutionary times. We propose a model by which CR elements might influence chromosome and genome size.

[Robotic rectal resection in rectal cancer: short term results in a monocentric prospective study].

PubMed

Bianchi, P; Petz, W; Spinoglio, G; Belotti, D; Bertani, E; Zampino, M G; Crosta, C; Lazzari, R; Andreoni, B

2011-12-01

The aim of this study was to evaluate technical feasibility, oncological safety and short-term clinical results of robotic rectal resection for cancer. From January 2008 to July 2010, 46 patients (27 males and 19 females, median age 69 years, median BMI 24.6 kg/m2) with histologically-proven adenocarcinoma of medium and distal rectum were enrolled in a prospective database. Preoperative assessment was performed with colonoscopy with biopsies, thoraco-abdominal CT scan, pelvic MRI and endorectal-ultrasound (ERUS). In the case of locally advanced non metastatic disease (T3/4 or N1/2), patients received preoperative radiotherapy (45 Grays in 5 weeks) and chemotherapy (oral Capecitabine). The robotic system was a four-arms Da Vinci® (Intuitive Surgical, Sunnyvale, CA, USA); arms position is not modified during the entire surgical procedure. Twenty-five patients received a preoperative radio-chemotherapy. Surgical procedure was an abdomino-perineal amputation in nine patients and an anterior resection in the remaining 37, with temporary ileostomy in 16 cases and a laparoscopic mobilization of splenic flexure in 25. Median operative time was 251 minutes, median time of first bowel movements 1.7 days and median hospital stay 6.7 days. Major complications requiring reoperation verified in 2 patients, while overall complication rate is 15.2%. Median number of harvested lymph nodes per patient was 18; median distance of the tumour from distal resection margin was 2 cm; distance of the tumour from circumferential margin was superior to 1 mm in all of the patients. At a median follow up of 11 months, all patients are alive and disease-free. Robotic rectal resection is a feasible technique which can provide good oncological and short-term clinical results.

Long-Term Outcomes With Intraoperative Radiotherapy as a Component of Treatment for Locally Advanced or Recurrent Uterine Sarcoma

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

Barney, Brandon M., E-mail: barney.brandon@mayo.edu; Petersen, Ivy A.; Dowdy, Sean C.

2012-05-01

Purpose: To report our institutional experience with intraoperative radiotherapy (IORT) as a component of treatment for women with locally advanced or recurrent uterine sarcoma. Methods and Materials: From 1990 to 2010, 16 women with primary (n = 3) or locoregionally recurrent (n = 13) uterine sarcoma received IORT as a component of combined modality treatment. Tumor histology studies found leiomyosarcoma (n = 9), endometrial stromal sarcoma (n = 4), and carcinosarcoma (n = 3). Surgery consisted of gross total resection in 2 patients, subtotal resection in 6 patients, and resection with close surgical margins in 8 patients. The median IORTmore » dose was 12.5 Gy (range, 10-20 Gy). All patients received perioperative external beam radiotherapy (EBRT; median dose, 50.4 Gy; range, 20-62.5 Gy), and 6 patients also received perioperative systemic therapy. Results: Seven of the 16 patients are alive at a median follow-up of 44 months (range, 11-203 months). The 3-year Kaplan-Meier estimate of local relapse (within the EBRT field) was 7%, and central control (within the IORT field) was 100%. No local failures occurred in any of the 6 patients who underwent subtotal resection. The 3-year freedom from distant relapse was 48%, with failures occurring most frequently in the lungs or mediastinum. Median survival was 18 months, and 3-year Kaplan-Meier estimates of cause-specific and overall survival were 58% and 53%, respectively. Three patients (19%) experienced late Grade 3 toxicity. Conclusions: A combined modality approach with perioperative EBRT, surgery, and IORT for locally advanced or recurrent uterine sarcoma resulted in excellent local disease control with acceptable toxicity, even in patients with positive resection margins. With this approach, some patients were able to experience long-term freedom from recurrence.« less

Real-Time Intraoperative Detection of Breast Cancer using Near-infrared Fluorescence Imaging and Methylene Blue

PubMed Central

Tummers, Quirijn R.J.G.; Verbeek, Floris P.R.; Schaafsma, Boudewijn E.; Boonstra, Martin C.; van der Vorst, Joost R.; Liefers, Gerrit-Jan; van de Velde, Cornelis J.H.; Frangioni, John V.; Vahrmeijer, Alexander L.

2014-01-01

Background Despite recent developments in preoperative breast cancer imaging, intraoperative localization of tumor tissue can be challenging, resulting in tumor-positive resection margins during breast-conserving surgery. Based on certain physicochemical similarities between Technetium(99mTc)-sestamibi (MIBI), a SPECT radiodiagnostic with a sensitivity of 83–90% to detect breast cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue (MB), we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging. Methods Twenty-four patients with breast cancer, planned for surgical resection, were included. Patients were divided in 2 administration groups, which differed with respect to the timing of MB administration. N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery. The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department. Results were confirmed by NIR fluorescence microscopy. Results 20/24 (83%) of breast tumors (carcinoma in N=21 and ductal carcinoma in situ in N=3) were identified in the resected specimen using NIR fluorescence imaging. Patients with non-detectable tumors were significantly older. No significant relation to receptor status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4 ± 0.8. There was no significant difference between TBR and background signal between administration groups. In 2/4 patients with positive resection margins, breast cancer tissue identified in the wound bed during surgery would have changed surgical management. Histology confirmed the concordance of fluorescence signal and tumor tissue. Conclusions This feasibility study demonstrated an overall breast cancer identification rate using MB of 83%, with real-time intraoperative guidance having the potential to alter patient management. PMID:24862545

Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue.

PubMed

Tummers, Q R J G; Verbeek, F P R; Schaafsma, B E; Boonstra, M C; van der Vorst, J R; Liefers, G-J; van de Velde, C J H; Frangioni, J V; Vahrmeijer, A L

2014-07-01

Despite recent developments in preoperative breast cancer imaging, intraoperative localization of tumor tissue can be challenging, resulting in tumor-positive resection margins during breast conserving surgery. Based on certain physicochemical similarities between Technetium((99m)Tc)-sestamibi (MIBI), an SPECT radiodiagnostic with a sensitivity of 83-90% to detect breast cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue (MB), we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging. Twenty-four patients with breast cancer, planned for surgical resection, were included. Patients were divided in 2 administration groups, which differed with respect to the timing of MB administration. N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery. The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department. Results were confirmed by NIR fluorescence microscopy. 20/24 (83%) of breast tumors (carcinoma in N = 21 and ductal carcinoma in situ in N = 3) were identified in the resected specimen using NIR fluorescence imaging. Patients with non-detectable tumors were significantly older. No significant relation to receptor status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4 ± 0.8. There was no significant difference between TBR and background signal between administration groups. In 2/4 patients with positive resection margins, breast cancer tissue identified in the wound bed during surgery would have changed surgical management. Histology confirmed the concordance of fluorescence signal and tumor tissue. This feasibility study demonstrated an overall breast cancer identification rate using MB of 83%, with real-time intraoperative guidance having the potential to alter patient management. Copyright © 2014 Elsevier Ltd. All rights reserved.

Deep pelvic anatomy revisited for a description of crucial steps in extralevator abdominoperineal excision for rectal cancer.

PubMed

Stelzner, Sigmar; Holm, Torbjörn; Moran, Brendan J; Heald, Richard J; Witzigmann, Helmut; Zorenkov, Dimitri; Wedel, Thilo

2011-08-01

Extralevator abdominoperineal excision results in superior oncologic outcome for advanced low rectal cancer. The exact definition of surgical resection planes is pivotal to achieving negative circumferential resection margins. This study aims to describe the surrounding anatomical structures that are at risk for inadvertent damage during extralevator abdominoperineal excision. Joint surgical and macroanatomical dissection was performed in a university laboratory of clinical anatomy. A stepwise dissection study was conducted according to the technique of extralevator abdominoperineal excision by abdominal and perineal approaches in 4 human cadaveric pelvises. Muscular, fascial, tendinous, and neural structures were carefully exposed and related to the corresponding surgical resection planes. In addition to the autonomic nerves to be identified and preserved during total mesorectal excision, further structures endangered during extralevator abdominoperineal excision can be clearly identified. Terminal pudendal nerve branches come close to the surgical resection plane at the outer surface of the puborectal sling. Likewise, the pelvic plexus and its neurovascular bundles embedded within the parietal pelvic fascia extend close to the apex of the prostate where the parietal pelvic fascia has to be divided. These neural structures converge in the region of the perineal body, an area that provides no "self-opening" planes for surgical dissection. Thus, the necessity to sharply detach the anorectal specimen anteriorly from the perineal body and the superficial transverse perineal muscle bears the risk of both inadvertent damage of the aforementioned anatomical structures and perforation of the specimen. The study focused primarily on the macroscopic topography relevant to the surgical procedure, so that previously published histologic examinations were not performed. The present anatomical dissection study highlights those anatomical landmarks that require clear identification for the successful achievement of both negative circumferential resection margins and preservation of urogenital functions during extralevator abdominoperineal excision.

[The Efficiency and Complications of ESD and ESTD in the Treatment of Large Esophageal Mucosal Lesions].

PubMed

Wang, Jin; Qin, Jin-yu; Guo, Tian-jiao; Gan, Tao; Wang, Yi-ping; Wu, Jun-chao

2015-11-01

To study the efficiency and complications of endoscopic submucosal dissection (ESD) and endoscopic submucosal tunnel dissection (ESTD) in the treatment of large esophageal mucosal lesions. The clinical data were collected from the patients who received ESD or ESTD for the treatment of early esophageal lesions in our hospital during January 1, 2014 to July 15, 2015, including the en bloc resection rate, curative resection rate, postoperative complication rate, the risk factors of complications were explored by univariate and multivariate analysis. A total of 50 patients were involved in the study, ESD or ESTD were performed successfully in 53 times, including 6 cases of ESD,47 cases of ESTD, The average age was (61.9 +/- 6.8) yr., the average operating time was (83.57 +/- 32.33) min, the average dissected lesion was (14.82 +/- 3.18) cm2, En bloc resection rate was 94.34%, the curative rate was 84.90%. There were 1 case of bleeding, 1 case of perforation, 45 (84.90%) cases of fever, 13 cases (24.53%) of esophageal stricture. The severity of stricture was associated with the operation time Codds ratio (OR) = 1.040, 95% confidence interal (CI): 1.007-1.075) and esophageal circumference (OR=9.972, 95% CI: 1.221-81.416). The residual resection margin appeared in 8 patients, and the lesion area (OR=1.145, 95% CI: 1.013-1.294) was the only risk factor. ESD and ESTD are safe and effective in the treatment of early esophageal lesions, but seems have relatively high incidence of esopgageal stricture and residual resection margin in the treatment of large esophageal lesions.

Laparoscopic complete mesocolic excision with central vascular ligation in right colon cancer: Long-term oncologic outcome between mesocolic and non-mesocolic planes of surgery.

PubMed

Siani, L M; Pulica, C

2015-12-01

To analyze our experience in translating the concept of total mesorectal excision to "no-touch" complete removal of an intact mesocolonic envelope (complete mesocolic excision), along with central vascular ligation and apical node dissection, in the surgical treatment of right-sided colonic cancers, comparing "mesocolic" to less radical "non-mesocolic" planes of surgery in respect to quality of the surgical specimen and long-term oncologic outcome. A total of 115 patients with right-sided colonic cancers were retrospectively enrolled from 2008 to 2013 and operated on following the intent of minimally invasive complete mesocolic excision with central vascular ligation. Morbidity and mortality were 22.6% and 1.7%, respectively. Mesocolic, intramesocolic, and muscularis propria planes of resection were achieved in 65.2%, 21.7%, and 13% of cases, respectively, with significant impact for mesenteric plane of surgery on R0 resection rate (97.3%), circumferential resection margin <1 mm (2.6%), and consequent survival advantage (82.6% at 5 years) when compared to muscularis propria plane of surgery, with R0 resection rate and overall survival falling to 72% and 60%, respectively, and with circumferential resection margin <1 mm raising to 33.3%, all being statistically significant. Stratifying patients for stage of disease, laparoscopic complete mesocolic excision with central vascular ligation significantly impacted survival in patients with stage II, IIIA/B, and in a subgroup of IIIC patients with negative apical nodes. In our experience, minimally invasive complete mesocolic excision with central vascular ligation allows for both safety and higher quality of surgical specimens when compared to less radical intramesocolic or muscularis propria planes of "standard" surgery, significantly impacting loco-regional control and thus overall survival. © The Finnish Surgical Society 2014.

The Implementation of CRM at FISC Norfolk Detachment Philadelphia

DTIC Science & Technology

2003-06-01

Customer Relationship Management system. [28] If FISC decides to implement a CRM system, the decision will impact the duties of the...distribution is unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) Customer Relations Management ( CRM ) can be defined in many ways. In...Norfolk Philadelphia Mission Statement. 15. NUMBER OF PAGES 91 14. SUBJECT TERMS Customer Relations Management System, CRM ,

Avoid the four perils of CRM.

PubMed

Rigby, Darrell K; Reichheld, Frederick F; Schefter, Phil

2002-02-01

Customer relationship management is one of the hottest management tools today. But more than half of all CRM initiatives fail to produce the anticipated results. Why? And what can companies do to reverse that negative trend? The authors--three senior Bain consultants--have spent the past ten years analyzing customer-loyalty initiatives, both successful and unsuccessful, at more than 200 companies in a wide range of industries. They've found that CRM backfires in part because executives don't understand what they are implementing, let alone how much it will cost or how long it will take. The authors' research unveiled four common pitfalls that managers stumble into when trying to implement CRM. Each pitfall is a consequence of a single flawed assumption--that CRM is software that will automatically manage customer relationships. It isn't. Rather, CRM is the creation of customer strategies and processes to build customer loyalty, which are then supported by the technology. This article looks at best practices in CRM at several companies, including the New York Times Company, Square D, GE Capital, Grand Expeditions, and BMC Software. It provides an intellectual framework for any company that wants to start a CRM program or turn around a failing one.

[Hepatocellular carcinoma originated in the caudate lobe. Surgical strategy for resection. A propos of a case].

PubMed

Martínez-Mier, Gustavo; Esquivel-Torres, Sergio; Calzada-Grijalva, José Francisco; Grube-Pagola, Peter

2015-01-01

Hepatocellular carcinoma originating from the caudate lobe has a worse prognosis than other hepatocellular carcinoma in another segment of the liver. An isolated caudate lobe resection of the liver represents a significant technical challenge. Caudate lobe resection can be performed along with a lobectomy or as an isolated liver resection. There are very few reports about isolated caudate lobe liver resection. We report a case of successful isolated resection of hepatocellular carcinoma in the caudate lobe with excellent long-term survival. A 74 years old female with 8cm mass lesion in the caudate lobe without clinical or biochemical evidence of liver cirrhosis, serum alpha-fetoprotein 3.7 U/l, and negative hepatitis serology was evaluated for surgery. Complete resection of the lesion in 270minutes with Pringle maneuver for 13minutes was satisfactorily performed. Patient was discharged ten days after surgery without complications. Patient is currently asymptomatic, without deterioration of liver function and 48 month tumor free survival after the procedure. Isolated caudate lobe resection is an uncommon but technically possible procedure. In order to achieve a successful resection, one must have a detailed knowledge of complete liver anatomy. Tumor free margins must be obtained to provide long survival for these patients who have a malignancy in this anatomic location. Copyright © 2015. Published by Masson Doyma México S.A.

crm-1 facilitates BMP signaling to control body size in Caenorhabditis elegans.

PubMed

Fung, Wong Yan; Fat, Ko Frankie Chi; Eng, Cheah Kathryn Song; Lau, Chow King

2007-11-01

We have identified in Caenorhabditis elegans a homologue of the vertebrate Crim1, crm-1, which encodes a putative transmembrane protein with multiple cysteine-rich (CR) domains known to have bone morphogenetic proteins (BMPs) binding activity. Using the body morphology of C. elegans as an indicator, we showed that attenuation of crm-1 activity leads to a small body phenotype reminiscent of that of BMP pathway mutants. We showed that the crm-1 loss-of-function phenotype can be rescued by constitutive supply of sma-4 activity. crm-1 can enhance BMP signaling and this activity is dependent on the presence of the DBL-1 ligand and its receptors. crm-1 is expressed in neurons at the ventral nerve cord, where the DBL-1 ligand is produced. However, ectopic expression experiments reveal that crm-1 gene products act outside the DBL-1 producing cells and function non-autonomously to facilitate dbl/sma pathway signaling to control body size.

The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

PubMed

Booth, David S; Cheng, Yifan; Frankel, Alan D

2014-12-08

The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

Patient-specific instrument can achieve same accuracy with less resection time than navigation assistance in periacetabular pelvic tumor surgery: a cadaveric study.

PubMed

Wong, Kwok-Chuen; Sze, Kwan-Yik; Wong, Irene Oi-Ling; Wong, Chung-Ming; Kumta, Shekhar-Madhukar

2016-02-01

Inaccurate resection in pelvic tumors can result in compromised margins with increase local recurrence. Navigation-assisted and patient-specific instrument (PSI) techniques have recently been reported in assisting pelvic tumor surgery with the tendency of improving surgical accuracy. We examined and compared the accuracy of transferring a virtual pelvic resection plan to actual surgery using navigation-assisted or PSI technique in a cadaver study. We performed CT scan in twelve cadaveric bodies including whole pelvic bones. Either supraacetabular or partial acetabular resection was virtually planned in a hemipelvis using engineering software. The virtual resection plan was transferred to a CT-based navigation system or was used for design and fabrication of PSI. Pelvic resections were performed using navigation assistance in six cadavers and PSI in another six. Post-resection images were co-registered with preoperative planning for comparative analysis of resection accuracy in the two techniques. The mean average deviation error from the planned resection was no different ([Formula: see text]) for the navigation and the PSI groups: 1.9 versus 1.4 mm, respectively. The mean time required for the bone resection was greater ([Formula: see text]) for the navigation group than for the PSI group: 16.2 versus 1.1 min, respectively. In simulated periacetabular pelvic tumor resections, PSI technique enabled surgeons to reproduce the virtual surgical plan with similar accuracy but with less bone resection time when compared with navigation assistance. Further studies are required to investigate the clinical benefits of PSI technique in pelvic tumor surgery.

Therapeutic outcomes of endoscopic submucosal dissection of differentiated early gastric cancer in a Western endoscopy setting (with video).

PubMed

Emura, Fabian; Mejía, Juan; Donneys, Alberto; Ricaurte, Orlando; Sabbagh, Luis; Giraldo-Cadavid, Luis; Oda, Ichiro; Saito, Yutaka; Osorio, Camilo

2015-11-01

Large multicenter gastric cancer endoscopic submucosal dissection (ESD) studies conducted at major Japanese institutions have reported en bloc resection, en bloc tumor-free margin resection, and curative resection rates of 92.7% to 96.1%, 82.6% to 94.5%, and 73.6% to 85.4%, respectively, with delayed bleeding and perforation rates of 0.6% to 6.0% and 3.6% to 4.7%, respectively. Although ESD is currently an alternative treatment in some countries, particularly in Asia, it remains uncertain whether ESD therapeutic outcomes in Western endoscopy settings can be comparable to those achieved in Japan. To evaluate the ESD therapeutic outcomes for differentiated early gastric cancer (EGC) in a Western endoscopy setting. Consecutive case series performed by an expertly trained Western endoscopist. Fifty-three patients with 54 lesions. ESD for early gastric cancers (T1) satisfying expanded inclusion criteria. En bloc resection, en bloc tumor-free margin resection, and curative resection rates were 98%, 93%, and 83%, respectively. The delayed bleeding rate was 7%, and the perforation rate was 4%. The mean patient age was 67 years, and the mean tumor size was 19.8 mm, with 54% of the lesions located in the lesser curvature. The median procedure time was 61 minutes, with ESD procedures 60 minutes or longer associated with submucosal fibrosis (P < .001) and tumor size 25 mm or larger (P = .03). In every ESD procedure, both circumferential incision and submucosal dissection were performed by using a single knife. Two of the 4 delayed bleeding cases required surgery, and all perforations were successfully managed by using endoscopic clips. Long-term outcome data are currently unavailable. ESD for differentiated EGC resulted in favorable therapeutic outcomes in a Western endoscopy setting comparable to those achieved at major Japanese institutions. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Social customer relationship management: taking advantage of Web 2.0 and Big Data technologies.

PubMed

Orenga-Roglá, Sergio; Chalmeta, Ricardo

2016-01-01

The emergence of Web 2.0 and Big Data technologies has allowed a new customer relationship strategy based on interactivity and collaboration called Social Customer Relationship Management (Social CRM) to be created. This enhances customer engagement and satisfaction. The implementation of Social CRM is a complex task that involves different organisational, human and technological aspects. However, there is a lack of methodologies to assist companies in these processes. This paper shows a novel methodology that helps companies to implement Social CRM, taking into account different aspects such as social customer strategy, the Social CRM performance measurement system, the Social CRM business processes, or the Social CRM computer system. The methodology was applied to one company in order to validate and refine it.

Mineral oil certified reference materials for the determination of polychlorinated biphenyls from the National Metrology Institute of Japan (NMIJ)

PubMed Central

Aoyagi, Yoshie; Matsuo, Mayumi; Ishikawa, Keiichiro; Hanari, Nobuyasu; Otsuka, Satoko; Tsuda, Yoko; Yarita, Takashi

2008-01-01

Four mineral oil certified reference materials (CRMs), NMIJ CRM 7902-a, CRM 7903-a, CRM 7904-a, and CRM 7905-a, have been issued by the National Metrology Institute of Japan, which is part of the National Institute of Advanced Industrial Science and Technology (NMIJ/AIST), for the determination of polychlorinated biphenyls (PCBs). The raw materials for the CRMs were an insulation oil (CRM 7902-a and CRM 7903-a) and a fuel oil (CRM7904-a and CRM 7905-a). A solution of PCB3, PCB8, and technical PCB products, comprising four types of Kaneclor, was added to the oil matrices. The total PCB concentrations in the PCB-fortified oils (CRM 7902-a and CRM 7904-a) are approximately 6 mg kg−1. In addition, the mineral oils which were not fortified with PCBs were also distributed as CRMs (CRM 7903-a and CRM 7905-a). Characterization of these CRMs was conducted by the NMIJ/AIST, where the mineral oils and the PCB solution were analyzed using multiple analytical methods such as dimethylsulfoxide extraction, normal-phase liquid chromatography, gel permeation chromatography, reversed-phase liquid chromatography, and chromatography using sulfoxide-bonded silica; and/or various capillary columns for gas chromatography, and two ionization modes for mass spectrometry. The target compounds in the mineral oils and those in the PCB solution were determined by one of the primary methods of measurement, isotope dilution–mass spectrometry (ID-MS). Certified values have been provided for 11 PCB congeners (PCB3, 8, 28, 52, 101, 118, 138, 153, 180, 194, and 206) in the CRMs. These CRMs have information values for PCB homologue concentrations determined by using a Japanese official method for determination of PCBs in wastes and densities determined with an oscillational density meter. Because oil samples having arbitrary PCB concentrations between respective property values of the PCB-fortified and nonfortified CRMs can be prepared by gravimetric mixing of the CRM pairs, these CRMs can be used for validation of PCB analyses using various instruments which have different sensitivities. Figure Preparation and certification processes of the mineral oil CRMs (example shown is polychlorinated biphenyls in insulation oil, high/low concentrations) Electronic supplementary material The online version of this article (doi:10.1007/s00216-008-2010-3) contains supplementary material, which is available to authorized users. PMID:18415091

Systematic implementation of clinical risk management in a large university hospital: the impact of risk managers.

PubMed

Sendlhofer, Gerald; Brunner, Gernot; Tax, Christa; Falzberger, Gebhard; Smolle, Josef; Leitgeb, Karina; Kober, Brigitte; Kamolz, Lars Peter

2015-01-01

For health care systems in recent years, patient safety has increasingly become a priority issue. National and international strategies have been considered to attempt to overcome the most prominent hazards while patients are receiving health care. Thereby, clinical risk management (CRM) plays a dominant role in enabling the identification, analysis, and management of potential risks. CRM implementation into routine procedures within complex hospital organizations is challenging, as in the past, organizational change strategies using a top-down approach have often failed. Therefore, one of our main objectives was to educate a certain number of risk managers in facilitating CRM using a bottom-up approach. To achieve our primary purpose, five project strands were developed, and consequently followed, introducing CRM: corporate governance, risk management (RM) training, CRM process, information, and involvement. The core part of the CRM process involved the education of risk managers within each organizational unit. To account for the size of the existing organization, we assumed that a minimum of 1 % of the workforce had to be trained in RM to disseminate the continuous improvement of quality and safety. Following a roll-out plan, CRM was introduced in each unit and potential risks were identified. Alongside the changes in the corporate governance, a hospital-wide CRM process was introduced resulting in 158 trained risk managers correlating to 2.0 % of the total workforce. Currently, risk managers are present in every unit and have identified 360 operational risks. Among those, 176 risks were scored as strategic and clustered together into top risks. Effective meeting structures and opportunities to share information and knowledge were introduced. Thus far, 31 units have been externally audited in CRM. The CRM approach is unique with respect to its dimension; members of all health care professions were trained to be able to identify potential risks. A network of risk managers supported the centrally coordinated CRM process. There is a strong commitment among management, academia, clinicians, and administration to foster cooperation. The introduction of CRM led to a visible shift with regard to patient safety culture throughout the entire organization. Still, there is a long way to go to keep people engaged in CRM and work on national and international patient safety initiatives to continuously decrease potential hazards.

[Oligometastasized colorectal cancer-modern treatment strategies].

PubMed

Binnebösel, M; Lambertz, A; Dejong, K; Neumann, U P

2018-06-05

The prognosis of colorectal cancer in UICC stage IV has been improved in the last decades by improvements in interdisciplinary treatment. Treatment strategies for oligometastasized colorectal cancer are developing more and more into an individualized treatment. An overview of the current literature of modern treatment concepts in oligometastasized colorectal cancer UICC stage IV is given. Surgery still has the supreme mandate in resectable colorectal liver metastases, as neoadjuvant and adjuvant treatment strategies to not provide any benefits for these patients. In marginal or non-resectable stages systemic treatment is superior in these patients depending on the prognostic parameters. Also in curative settings local treatment options should be considered as a reasonable additive tool. An interesting treatment approach for isolated liver metastases and non-resectable colorectal cancer is liver transplantation. Irrespective of new developments in treatment strategies for metastasized colorectal cancer, resection of colorectal liver metastases remains the gold standard whenever possible.

Current management of cholangiocarcinoma.

PubMed

Singh, Manoj K; Facciuto, Marcelo E

2012-01-01

Cholangiocarcinoma is the second most common primary hepatobiliary malignancy after hepatocellular carcinoma and remains among the most difficult management problems faced by surgeons. Curative surgery is achieved in only 25% to 30% of patients. Local tumor extent, such as portal vein invasion and hepatic lobar atrophy, does not preclude resection. Long-term survival has been seen only in patients who underwent extensive liver resections, suggesting that bile-duct excision alone is less effective. The majority of patients have unresectable disease, with 20% to 30% incidence of distant metastasis at presentation. Unresectable patients should be referred for nonsurgical biliary decompression, and in potential curative resection candidates the use of biliary stents should be reduced. Liver transplantation provides the option of wide resection margins, expanding the indication of surgical intervention for selected patients who otherwise are not surgical candidates due to lack of functional hepatic reserve. © 2012 Mount Sinai School of Medicine.

[Metastatic disease of the liver: surgical perspective].

PubMed

Mercado, M A; Medina, H; Rossano, A; Acosta, E; Rodríguez, M; Chan, C; Orozco, H

1997-01-01

Approximately half of patients with colorectal cancer will develop hepatic metastases and it is estimated that up to 10% of that group will have resectable liver disease. Surgical resection remains the first line treatment option of metastatic liver tumors and has yielded a 20 to 40% five year survival rate. Selection of appropriate patients for resection is critical to a successful outcome. The best results are obtained in patients with isolated metastases. Factors that are associated with a poorer results are the presence of four or more lesions or a surgical margin less than 1 cm. Endocrine metastases can be resected in a palliative fashion but each case has to be individualized. This is also true for non colorectal-nonendocrine metastases. For this tumors the experience is anecdotal and confined to limited reported series. Adjuvant treatment (infusional chemotherapy and chemoembolization) can also have a role in treatment as well as cryotherapy.

[Radiofrequency ablation of hepatocellular carcinoma].

PubMed

Widmann, Gerlig; Schullian, Peter; Bale, Reto

2013-03-01

Percutaneous radiofrequency ablation (RFA) is well established in the treatment of hepatocellular carcinoma (HCC). Due to its curative potential, it is the method of choice for non resectable BCLC (Barcelona Liver Clinic) 0 and A. RFA challenges surgical resection for small HCC and is the method of choice in bridging for transplantation and recurrence after resection or transplantation. The technical feasibility of RFA depends on the size and location of the HCC and the availability of ablation techniques (one needle techniques, multi-needle techniques). More recently, stereotactic multi-needle techniques with 3D trajectory planning and guided needle placement substantially improve the spectrum of treatable lesions including large volume tumors. Treatment success depends on the realization of ablations with large intentional margins of tumor free tissue (A0 ablation in analogy to R0 resection), which has to be documented by fusion of post- with pre-ablation images, and confirmed during follow-up imaging.

DDDAS-based Resilient Cyberspace (DRCS)

DTIC Science & Technology

2016-08-03

Resilient Middleware ( CRM ), Supervisor VMs (SVMs), and Master VMs (MVMs). In what follows, we briefly highlight the main functions to be provided by each...phases. 4.5.1.2 Cloud Resilient Middleware ( CRM ) The CRM provides the control and management services to deploy and configure the software and...To speedup the process of selecting the appropriate resilient algorithms and execution environments, the CRM repository contains a set of SBE

Role of Knowledge Management and Analytical CRM in Business: Data Mining Based Framework

ERIC Educational Resources Information Center

Ranjan, Jayanthi; Bhatnagar, Vishal

2011-01-01

Purpose: The purpose of the paper is to provide a thorough analysis of the concepts of business intelligence (BI), knowledge management (KM) and analytical CRM (aCRM) and to establish a framework for integrating all the three to each other. The paper also seeks to establish a KM and aCRM based framework using data mining (DM) techniques, which…

CRM Systems with Social Networking Capabilities: The Value of Incorporating a CRM 2.0 System in Sales/Marketing Education

ERIC Educational Resources Information Center

Wang, Xin; Dugan, Riley; Sojka, Jane

2013-01-01

Implementation of a customer relationship management (CRM) 2.0 system can provide both a valuable pedagogical tool and a needed skill set in a marketing and sales curriculum. A CRM 2.0 system incorporated in the sales and marketing curriculum can help manage relationships between students, practitioners, and faculty while teaching students a…

Defense AT and L. Volume 45, Number 3

DTIC Science & Technology

2016-06-01

CRM ). During the 1980s, the commercial airlines and military invested heavily in CRM training, aiming to increase crew coordination and improve...cockpit management. These CRM training programs focused on human factors train- ing—also called man-machine interfaces—with specific concentration on...leadership and decision making. CRM has evolved over the years with emphasis now placed on the acquisition of timely, appropriate infor- mation

Robot-assisted radical prostatectomy: Multiparametric MR imaging-directed intraoperative frozen-section analysis to reduce the rate of positive surgical margins.

PubMed

Petralia, Giuseppe; Musi, Gennaro; Padhani, Anwar R; Summers, Paul; Renne, Giuseppe; Alessi, Sarah; Raimondi, Sara; Matei, Deliu V; Renne, Salvatore L; Jereczek-Fossa, Barbara A; De Cobelli, Ottavio; Bellomi, Massimo

2015-02-01

To investigate whether use of multiparametric magnetic resonance (MR) imaging-directed intraoperative frozen-section (IFS) analysis during nerve-sparing robot-assisted radical prostatectomy reduces the rate of positive surgical margins. This retrospective analysis of prospectively acquired data was approved by an institutional ethics committee, and the requirement for informed consent was waived. Data were reviewed for 134 patients who underwent preoperative multiparametric MR imaging (T2 weighted, diffusion weighted, and dynamic contrast-material enhanced) and nerve-sparing robot-assisted radical prostatectomy, during which IFS analysis was used, and secondary resections were performed when IFS results were positive for cancer. Control patients (n = 134) matched for age, prostate-specific antigen level, and stage were selected from a pool of 322 patients who underwent nerve-sparing robot-assisted radical prostatectomy without multiparametric MR imaging and IFS analysis. Rates of positive surgical margins were compared by means of the McNemar test, and a multivariate conditional logistic regression model was used to estimate the odds ratio of positive surgical margins for patients who underwent MR imaging and IFS analysis compared with control subjects. Eighteen patients who underwent MR imaging and IFS analysis underwent secondary resections, and 13 of these patients were found to have negative surgical margins at final pathologic examination. Positive surgical margins were found less frequently in the patients who underwent MR imaging and IFS analysis than in control patients (7.5% vs 18.7%, P = .01). When the differences in risk factors are taken into account, patients who underwent MR imaging and IFS had one-seventh the risk of having positive surgical margins relative to control patients (adjusted odds ratio: 0.15; 95% confidence interval: 0.04, 0.61). The significantly lower rate of positive surgical margins compared with that in control patients provides preliminary evidence of the positive clinical effect of multiparametric MR imaging-directed IFS analysis for patients who undergo prostatectomy. © RSNA, 2014.

Awake surgery for WHO Grade II gliomas within "noneloquent" areas in the left dominant hemisphere: toward a "supratotal" resection. Clinical article.

PubMed

Yordanova, Yordanka N; Moritz-Gasser, Sylvie; Duffau, Hugues

2011-08-01

It has been demonstrated that an extensive resection (total or subtotal) may significantly increase the overall survival in patients with WHO Grade II gliomas (low-grade gliomas [LGGs]). Yet, recent data have shown that conventional MR imaging underestimates the spatial extent of LGG, since tumor cells were found up to 20 mm around MR imaging abnormalities. Thus, it was hypothesized that an extended resection with a margin beyond MR imaging-defined abnormalities-a "supratotal" resection-might improve the outcome of LGG. However, because of the frequent location of LGG within "eloquent" brain areas, it is often difficult to achieve such a supratotal resection. This could nevertheless be possible when LGGs involve "noneloquent" areas, even in the left dominant hemisphere. The authors report on their use of awake electrical mapping to tailor the resection according to functional boundaries, that is, to pursue the resection beyond MR imaging-defined abnormalities, until corticosubcortical eloquent structures are encountered. Their aim was to apply this reliable surgical technique to LGGs located not within eloquent areas but distant from eloquent areas, to take a margin around the LGG visible on MR imaging while preserving brain function. Fifteen right-handed patients with a total of 17 tumors underwent resection of WHO Grade II gliomas involving nonfunctional areas within the left dominant hemisphere. In all patients, seizures were the initial manifestation of the tumors. Awake surgery with intraoperative electrostimulation was performed in all cases. The resection was continued until the surgeon reached cortical and subcortical areas crucial for brain function, especially language, as defined by the intrasurgical electrical mapping. The extent of resection was evaluated on postoperative FLAIR-weighted MR images. Despite transient neurological worsening in 60% of cases, all patients recovered and returned to a normal life. Seizure control was obtained in all patients with a decrease of antiepileptic drug therapy. Postoperative MR imaging showed that total resection was achieved in all 17 tumors and supratotal resection in 15. The average volume of the postoperative cavity (36.8 cm(3)) was significantly larger than the mean preoperative tumor volume (26.6 cm(3)) (p = 0.009). Neuropathological examination confirmed the diagnosis of WHO Grade II glioma in all cases. The mean duration of postoperative follow-up was 35.7 months (range 6-135 months). Only 4 of 15 patients experienced recurrence (without anaplastic transformation); the average time to recurrence in these cases was 38 months; radiotherapy was performed 6 years after the relapse in 1 case; no other patients received any adjuvant treatment. This series was compared with a control group of 29 patients who had "only" complete resection: anaplastic transformation was observed in 7 cases in the control group but not in any case in the series of patients who underwent supracomplete resection (p = 0.037). Furthermore, adjuvant treatment was administered in 10 patients in the control group compared with 1 patient who underwent supracomplete resection (p = 0.043). These findings support the usefulness of awake surgery with intraoperative functional (language) mapping with the attempt to perform supratotal resection of LGGs involving noneloquent areas in the left hemisphere. Indeed, the extent of resection was significantly increased in all cases but 2, with no additional permanent deficit and with control of seizures in all patients. The goal of supracomplete resection is currently to delay the anaplastic transformation, even if it does not (yet) enable a cure.

Hydronephrosis does not preclude curative resection of pelvic recurrences after colorectal surgery.

PubMed

Henry, Leonard R; Sigurdson, Elin; Ross, Eric; Hoffman, John P

2005-10-01

In one third of patients who die of rectal cancer, a pelvic recurrence after resection represents isolated disease for which re-resection may provide cure. These extensive resections can carry high morbidity. Proper patient selection is desirable but difficult. Hydronephrosis has been documented previously to portend a poor prognosis, and some consider it a contraindication to attempted resection. It was our goal to review our experience and either confirm or refute these conclusions. We performed a retrospective analysis of 90 patients resected with curative intent for pelvic recurrence at our center from 1988 through 2003. Seventy-one records documented the preoperative presence or absence of hydronephrosis. Clinical and pathologic data were recorded. The groups with and without hydronephrosis were compared. There were 15 patients with hydronephrosis in this study and 56 without. Although patients with hydronephrosis had shorter overall survival, disease-free survival, and rate of local control, none of these differences was statistically significant. Patients in the hydronephrosis group were younger and had higher-stage primary tumors and larger recurrent tumors. Subsequently, they underwent more extensive resections and were more likely to be treated with adjuvant therapies. There was no difference in the rate of margin-negative resections between the groups. Hydronephrosis correlates with younger patients with larger recurrent tumors undergoing more extensive operations and multimodality therapy but does not preclude curative (R0) resection or independently affect overall survival, disease-free survival, or local control. We believe that it should not be considered a contraindication to attempting curative resection.

[Surgical management of retroperitoneal soft-tissue sarcomas--an overview].

PubMed

Garlipp, B; Schulz, H-U; Zeile, M; Lippert, H; Meyer, F

2010-12-01

Retroperitoneal soft-tissue sarcomas (RSTS) represent a rare and heterogeneous class of diseases for which the clinical management is still largely non-standardised. Based on a selective review of recent publications, it was the purpose of the present review article to summarize the current concepts of disease classification, diagnostics and surgical as well as multimodal therapy for these tumors. A clinically based empirical review derived from a literature search focusing on publications from the past 5  years was carried out. Due to the paucity of randomised-controlled trials, therapy for RSTS is largely based on personal experience, retrospectively gathered data and historical controls. Pre-therapeutic planning requires precise information on the localisation, extension, and texture of the tumor through cross-sectional imaging (CT, MRI) as well as histological diagnosis through percutaneous or open biopsy. Complete tumor resection is crucial. Recent studies have confirmed the importance of microscopically negative resection margins which has subsequently led to a trend towards more radical resection. Chemotherapy does not play a role in the adjuvant setting except in clinical trials; however, radiotherapy has been controversely debated in adjuvant RSTS therapy. Efforts to limit radiation toxicity include modern techniques as well as a strategy of using pre-resection radiotherapy instead of postoperative radiation. Surgery is also the treatment of choice for locally recurrent RSTS and pulmonary metastases. The prognosis of RSTS depends on the quality of surgical care and several disease-specific factors (histological type, grading). The clinical management of RSTS is complex and can only partly be considered as evidence-based. Due to the required level of experience in the treatment of these tumor lesions and the involvement of several subspecialties, pre-therapeutic planning, treatment and follow-up should be limited to high-volume surgical centres. In order to achieve microscopically negative resection margins, multivisceral resections are a valuable option after thorough consideration of the risks and benefits. Adjuvant radiotherapy needs to be decided upon on an individual basis, taking into account patient- and tumor-specific factors as well as resection status. © Georg Thieme Verlag Stuttgart ˙ New York.

Carrier priming with CRM 197 or diphtheria toxoid has a different impact on the immunogenicity of the respective glycoconjugates: biophysical and immunochemical interpretation.

PubMed

Pecetta, S; Lo Surdo, P; Tontini, M; Proietti, D; Zambonelli, C; Bottomley, M J; Biagini, M; Berti, F; Costantino, P; Romano, M R

2015-01-03

Glycoconjugate vaccines play an enormous role in preventing infectious diseases. The main carrier proteins used in commercial conjugate vaccines are the non-toxic mutant of diphtheria toxin (CRM197), diphtheria toxoid (DT) and tetanus toxoid (TT). Modern childhood routine vaccination schedules include the administration of several vaccines simultaneously or in close sequence, increasing the concern that the repeated exposure to conjugates based on these carrier proteins might interfere with the anti-polysaccharide response. Extending previous observations we show here that priming mice with CRM197 or DT does not suppress the response to the carbohydrate moiety of CRM197 meningococcal serogroup A (MenA) conjugates, while priming with DT can suppress the response to DT-MenA conjugates. To explain these findings we made use of biophysical and immunochemical techniques applied mainly to MenA conjugates. Differential scanning calorimetry and circular dichroism data revealed that the CRM197 structure was altered by the chemical conjugation, while DT and the formaldehyde-treated form of CRM197 were less impacted, depending on the degree of glycosylation. Investigating the binding and avidity properties of IgGs induced in mice by non-conjugated carriers, we found that CRM197 induced low levels of anti-carrier antibodies, with decreased avidity for its MenA conjugates and poor binding to DT and respective MenA conjugates. In contrast, DT induced high antibody titers able to bind with comparable avidity both the protein and its conjugates but showing very low avidity for CRM197 and related conjugates. The low intrinsic immunogenicity of CRM197 as compared to DT, the structural modifications induced by glycoconjugation and detoxification processes, resulting in conformational changes in CRM197 and DT epitopes with consequent alteration of the antibody recognition and avidity, might explain the different behavior of CRM197 and DT in a carrier priming context. Copyright © 2014 Elsevier Ltd. All rights reserved.

Raman spectroscopy reveals biophysical markers in skin cancer surgical margins

NASA Astrophysics Data System (ADS)

Feng, Xu; Moy, Austin J.; Nguyen, Hieu T. M.; Zhang, Yao; Fox, Matthew C.; Sebastian, Katherine R.; Reichenberg, Jason S.; Markey, Mia K.; Tunnell, James W.

2018-02-01

The recurrence rate of nonmelanoma skin cancer is highly related to the residual tumor after surgery. Although tissueconserving surgery, such as Mohs surgery, is a standard method for the treatment of nonmelanoma skin cancer, they are limited by lengthy and costly frozen-section histopathology. Raman spectroscopy (RS) is proving to be an objective, sensitive, and non-destructive tool for detecting skin cancer. Previous studies demonstrated the high sensitivity of RS in detecting tumor margins of basal cell carcinoma (BCC). However, those studies rely on statistical classification models and do not elucidate the skin biophysical composition. As a result, we aim to discover the biophysical differences between BCC and primary normal skin structures (including epidermis, dermis, hair follicle, sebaceous gland and fat). We obtained freshly resected ex vivo skin samples from fresh resection specimens from 14 patients undergoing Mohs surgery. Raman images were acquired from regions containing one or more structures using a custom built 830nm confocal Raman microscope. The spectra were grouped using K-means clustering analysis and annotated as either BCC or each of the five normal structures by comparing with the histopathology image of the serial section. The spectral data were then fit by a previously established biophysical model with eight primary skin constituents. Our results show that BCC has significant differences in the fit coefficients of nucleus, collagen, triolein, keratin and elastin compared with normal structures. Our study reveals RS has the potential to detect biophysical changes in resection margins, and supports the development of diagnostic algorithms for future intraoperative implementation of RS during Mohs surgery.

Results of NCCTG N0275 (Alliance) - a phase II trial evaluating resection followed by adjuvant radiation therapy for patients with desmoplastic melanoma.

PubMed

Rule, William G; Allred, Jacob B; Pockaj, Barbara A; Markovic, Svetomir N; DiCaudo, David J; Erickson, Lori A; Deming, Richard L; Schild, Steven E

2016-08-01

To examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin-negative, and nonmetastatic DM were eligible for this single-arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2- to 3-cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2-year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression-free survival, overall survival (OS), and treatment-related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2-year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin-negative WLE. Additional study is needed to further refine low-risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Safety and immunogenicity of a novel quadrivalent meningococcal CRM-conjugate vaccine given concomitantly with routine vaccinations in infants.

PubMed

Klein, Nicola P; Reisinger, Keith S; Johnston, William; Odrljin, Tatjana; Gill, Christopher J; Bedell, Lisa; Dull, Peter

2012-01-01

In phase II studies, MenACWY-CRM elicited robust immunologic responses in young infants. We now present results from our pivotal phase III infant immunogenicity/safety study. In this open-label phase III study, we randomized full-term 2-month-old infants to 4 doses of MenACWY-CRM coadministered with routine vaccines at 2, 4, 6, and 12 months of age or with routine vaccines alone. We monitored for local and systemic reactions and serious adverse events among all study participants and evaluated for sufficiency of the immune responses to MenACWY-CRM through serum bactericidal activity assay with human complement. Bactericidal antibodies were present in 94% to 100% of subjects against each of the serogroups in MenACWY-CRM after the 4-dose series and were 67% to 97% after the first 3 doses. Geometric mean titers were higher after the fourth dose of MenACWY-CRM compared with a single dose of MenACWY-CRM at 12 months of age for all serogroups (range of ratios, 4.5-38). Responses to 3 doses of routine vaccines coadministered with MenACWY-CRM were noninferior to routine vaccinations alone, except for small differences in pneumococcal serotype 6B responses after dose 3 but not dose 4 and pertactin after dose 3. Inclusion of MenACWY-CRM did not affect the safety or reactogenicity profiles of the routine infant vaccine series. A 4-dose series of MenACWY-CRM was highly immunogenic and well tolerated in young infants, and it can be coadministered with routine infant vaccines. Substantial immunity was conferred after the first 3 doses administered at 2, 4, and 6 months of age.

CRM1 and its ribosome export adaptor NMD3 localize to the nucleolus and affect rRNA synthesis.

PubMed

Bai, Baoyan; Moore, Henna M; Laiho, Marikki

2013-01-01

CRM1 is an export factor that together with its adaptor NMD3 transports numerous cargo molecules from the nucleus to cytoplasm through the nuclear pore. Previous studies have suggested that CRM1 and NMD3 are detected in the nucleolus. However, their localization with subnucleolar domains or participation in the activities of the nucleolus are unclear. We demonstrate here biochemically and using imaging analyses that CRM1 and NMD3 co-localize with nucleolar marker proteins in the nucleolus. In particular, their nucleolar localization is markedly increased by inhibition of RNA polymerase I (Pol I) transcription by actinomycin D or by silencing Pol I catalytic subunit, RPA194. We show that CRM1 nucleolar localization is dependent on its activity and the expression of NMD3, whereas NMD3 nucleolar localization is independent of CRM1. This suggests that NMD3 provides nucleolar tethering of CRM1. While inhibition of CRM1 by leptomycin B inhibited processing of 28S ribosomal (r) RNA, depletion of NMD3 did not, suggesting that their effects on 28S rRNA processing are distinct. Markedly, depletion of NMD3 and inhibition of CRM1 reduced the rate of pre-47S rRNA synthesis. However, their inactivation did not lead to nucleolar disintegration, a hallmark of Pol I transcription stress, suggesting that they do not directly regulate transcription. These results indicate that CRM1 and NMD3 have complex functions in pathways that couple rRNA synthetic and processing engines and that the rRNA synthesis rate may be adjusted according to proficiency in rRNA processing and export.

Clinical risk management in mental health: a qualitative study of main risks and related organizational management practices

PubMed Central

2013-01-01

Background A scientific understanding of clinical risk management (CRM) in mental health care is essential for building safer health systems and for improving patient safety. While evidence on patient safety and CRM in physical health care has increased, there is limited research on these issues in mental health care. This qualitative study provides an overview of the most important clinical risks in mental health and related organizational management practices. Methods We conducted in-depth expert interviews with professionals responsible for CRM in psychiatric hospitals. Interviews were transcribed and analyzed applying qualitative content analysis to thematically sort the identified risks. Results The main concerns for CRM in mental health are a) violence and self-destructive behavior (i.e. protecting patients and staff from other patients, and patients from themselves), b) treatment errors, especially in the process of therapy, and c) risks associated with mental illnesses (e.g. psychosis or depression). This study identified critical differences to CRM in hospitals for physical disorder and challenges specific to CRM in mental health. Firstly, many psychiatric patients do not believe that they are ill and are therefore in hospital against their will. Secondly, staff safety is a much more prominent theme for CRM in mental health care as it is directly related to the specifics of mental illnesses. Conclusions The current study contributes to the understanding of patient safety and raises awareness for CRM in mental health. The mental health specific overview of central risks and related organizational management practices offers a valuable basis for CRM development in mental health and an addition to CRM in general. PMID:23379842

Introduction to MAC CRM training

NASA Technical Reports Server (NTRS)

Brown, Donald D.

1987-01-01

The author introduces the Military Airlift Command (MAC) and its mission. A brief history of Cockpit Resource Management (CRM) as it relates to MAC is given. He also states why MAC is currently interested in CRM.

Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.

PubMed

Stamboulian, D; Lopardo, G; Lopez, P; Cortes-Barbosa, C; Valencia, A; Bedell, L; Karsten, A; Dull, P M

2010-10-01

This study compared the investigational quadrivalent meningococcal CRM₁₉₇ conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2- to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Co-administration of a meningococcal glycoconjugate ACWY vaccine with travel vaccines: a randomized, open-label, multi-center study.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Meyer, Seetha; Forleo-Neto, Eduardo; Gniel, Dieter; Dagnew, Alemnew F; Arora, Ashwani Kumar

2014-01-01

Potential interactions between vaccines may compromise the immunogenicity and/or safety of individual vaccines so must be assessed before concomitant administration is recommended. In this study, the immunogenicity and safety of travel vaccines against Japanese encephalitis (JEV) and rabies (PCECV) administered together with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine were evaluated (NCT01466387). Healthy adults aged 18 to ≤60 years were randomized to one of four vaccine regimens: JEV + PCECV + MenACWY-CRM, JEV + PCECV, PCECV or MenACWY-CRM. Immunogenicity at baseline and 28 days post-complete vaccination was assessed by serum bactericidal assay using human complement or neutralization tests. Adverse events (AEs) were collected throughout the study period. JEV + PCECV + MenACWY-CRM was non-inferior to JEV + PCECV. Post-vaccination seroprotective neutralizing titers or concentrations were achieved in 98-99% (JE) and 100% (rabies) of subjects across the vaccine groups. Antibody responses to vaccine meningococcal serogroups were in the same range for MenACWY-CRM and JEV + PCECV + MenACWY-CRM. Rates of reporting of AEs were similar for JEV + PCECV and JEV + PCECV + MenACWY-CRM. MenACWY-CRM was administered with an inactivated adjuvanted JE and a purified chick embryo cell-culture rabies vaccine without compromising immunogenicity or safety of the individual vaccines. These data provide evidence that MenACWY-CRM could be effectively incorporated into travel vaccination programs. NCT01466387. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel selective inhibitors of nuclear export CRM1 antagonists for therapy in mantle cell lymphoma.

PubMed

Zhang, Kejie; Wang, Michael; Tamayo, Archito T; Shacham, Sharon; Kauffman, Michael; Lee, John; Zhang, Liang; Ou, Zhishuo; Li, Changping; Sun, Luhong; Ford, Richard J; Pham, Lan V

2013-01-01

Overexpression of the cellular nuclear exportin 1, more commonly called chromosomal region maintenance 1 (CRM1), has been associated with malignant progression and mortality. Therefore, activation of nuclear export can play a significant etiologic role in some forms of human neoplasia and serve as a novel target for the treatment of these cancers. Mantle cell lymphoma (MCL) is an aggressive histotype of B-cell non-Hodgkin lymphoma that remains incurable. The objective of this study was to investigate the functional significance of CRM1 in MCL by evaluating the therapeutic efficacy of CRM1 inhibition in MCL in vitro and in vivo. Our results showed that CRM1 is highly expressed in MCL cells and is involved in regulating growth and survival mechanisms through the critical nuclear factor-κB survival pathway, which is independent of p53 status. Inhibition of CRM1 by two novel selective inhibitors of nuclear export (SINE), KPT-185 and KPT-276, in MCL cells resulted in significant growth inhibition and apoptosis induction. KPT-185 also induced CRM1 accumulation in the nucleus, resulting in CRM1 degradation by the proteasome. Oral administration of KPT-276 significantly suppressed tumor growth in an MCL-bearing severe combined immunodeficient mouse model, without severe toxicity. Our data suggest that SINE CRM1 antagonists are a potential novel therapy for patients with MCL, particular in relapsed/refractory disease. Copyright © 2013 ISEH - Society for Hematology and Stem Cells. All rights reserved.

Cockpit Resource Management Proficiency as a Factor of Primary Flight Training

DTIC Science & Technology

1992-07-01

Cockpit Resource Management ( CRM ). CRM attempts to explain and address the need and importance of "the communication process in the cockpit, and an...6 Definition of Terms Cockpit Resource Management ( CRM ) : The effective use and coordination of all skills and resources- hardware, software, liveware...E. & Williams K. R. (1987). The Application of CRM to Military Operations. In: Cockpit Resource Management Training-NASA Conference’Publication 2455

Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression

PubMed Central

Dunipace, Leslie; Ozdemir, Anil; Stathopoulos, Angelike

2011-01-01

It has been shown in several organisms that multiple cis-regulatory modules (CRMs) of a gene locus can be active concurrently to support similar spatiotemporal expression. To understand the functional importance of such seemingly redundant CRMs, we examined two CRMs from the Drosophila snail gene locus, which are both active in the ventral region of pre-gastrulation embryos. By performing a deletion series in a ∼25 kb DNA rescue construct using BAC recombineering and site-directed transgenesis, we demonstrate that the two CRMs are not redundant. The distal CRM is absolutely required for viability, whereas the proximal CRM is required only under extreme conditions such as high temperature. Consistent with their distinct requirements, the CRMs support distinct expression patterns: the proximal CRM exhibits an expanded expression domain relative to endogenous snail, whereas the distal CRM exhibits almost complete overlap with snail except at the anterior-most pole. We further show that the distal CRM normally limits the increased expression domain of the proximal CRM and that the proximal CRM serves as a `damper' for the expression levels driven by the distal CRM. Thus, the two CRMs interact in cis in a non-additive fashion and these interactions may be important for fine-tuning the domains and levels of gene expression. PMID:21813571

CRM1 Inhibitors for Antiviral Therapy

PubMed Central

Mathew, Cynthia; Ghildyal, Reena

2017-01-01

Infectious diseases are a major global concern and despite major advancements in medical research, still cause significant morbidity and mortality. Progress in antiviral therapy is particularly hindered by appearance of mutants capable of overcoming the effects of drugs targeting viral components. Alternatively, development of drugs targeting host proteins essential for completion of viral lifecycle holds potential as a viable strategy for antiviral therapy. Nucleocytoplasmic trafficking pathways in particular are involved in several pathological conditions including cancer and viral infections, where hijacking or alteration of function of key transporter proteins, such as Chromosome Region Maintenance1 (CRM1) is observed. Overexpression of CRM1-mediated nuclear export is evident in several solid and hematological malignancies. Interestingly, CRM1-mediated nuclear export of viral components is crucial in various stages of the viral lifecycle and assembly. This review summarizes the role of CRM1 in cancer and selected viruses. Leptomycin B (LMB) is the prototypical inhibitor of CRM1 potent against various cancer cell lines overexpressing CRM1 and in limiting viral infections at nanomolar concentrations in vitro. However, the irreversible shutdown of nuclear export results in high cytotoxicity and limited efficacy in vivo. This has prompted search for synthetic and natural CRM1 inhibitors that can potentially be developed as broadly active antivirals, some of which are summarized in this review. PMID:28702009

Impact of surgical margins on survival of 37 dogs with massive hepatocellular carcinoma.

PubMed

Matsuyama, A; Takagi, S; Hosoya, K; Kagawa, Y; Nakamura, K; Deguchi, T; Takiguchi, M

2017-09-01

To compare the survival of dogs with completely resected massive hepatocellular carcinoma (HCC) with that of dogs in which HCC were incompletely excised. A retrospective cohort study was conducted. Dogs that underwent surgical excision of massive HCC between November 2006 and April 2015 were included. Dogs that died in the perioperative period or were lost to follow-up within 2 months after surgery were excluded. Data were collected from the medical records and a single pathologist examined all available histology slides to confirm the diagnosis of HCC. Surgical margins were defined as complete if no neoplastic cells were seen at the edge of excised tissues, based on original histopathology reports. Progression-free survival (PFS) and overall survival (OS) were compared between dogs with complete surgical margins (CM) and those with incomplete margins (IM) using a log-rank test. Of the 37 dogs included in the study, 25 were allocated to the CM group and 12 to the IM group. Progressive local disease developed after surgery in three dogs in the CM group and seven dogs in the IM group. Three dogs in the CM group and five dogs in the IM group died due to tumour progression. Median PFS was longer for dogs in the CM group (1,000 (95% CI=562-1,438) days) compared to dogs in the IM group (521 (95% CI=243-799) days; p=0.007). OS was also longer for dogs in the CM group (>1,836 days) compared to those in the IM group (median 765 (95% CI=474-1,056) days; p=0.02). Compared with complete resection, incomplete resection decreased PFS and OS in dogs with massive HCC. Dogs with incompletely excised HCC should be closely monitored for local recurrence, although median OS was >2 years following incomplete excision. Further prospective studies are warranted to confirm these findings.

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

PubMed

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

2015-05-01

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

Half forehead reconstruction with a single rotational scalp flap for dermatofibrosarcoma protuberans treatment.

PubMed

Mori, Stefano; Di Monta, Gianluca; Marone, Ugo; Chiofalo, Maria Grazia; Caracò, Corrado

2012-05-06

Dermatofibrosarcoma protuberans (DFSP) is a soft tissue neoplasm of intermediate to low-grade malignancy. Although metastasis rarely occurs, DFSP has a locally aggressive behavior with a high recurrence rate. In the head and neck area, resection involving a wide margin of healthy tissue can be difficult because of functional and cosmetic considerations. We describe a novel reconstructive method for half forehead defects with an innovative single local wide scalp flap following excision of DFSP with a 3 cm margin of healthy tissue. Two patients underwent wide resection of forehead DFSP and reconstruction with a single rotational scalp flap. The scalp flap blood supply was provided from three main vessels: the superficial temporal artery, occipital artery and posterior auricular artery. No early or late complications were observed in either patient with no local recurrence after 18 months of follow-up. The donor area could be closed primarily in both cases and the flaps survived completely. This innovative technique allowed a radical excision of forehead DFSP with sufficient healthy margins, thus potentially decreasing tumor recurrence rate. Reconstruction was achieved avoiding microsurgery, skin expanders and large skin grafts. Moreover, all main reconstructive criteria, such as functional and cosmetic tissue characteristics, were completely fulfilled.

[Management and complications of tumor resections of the midface].

PubMed

Beule, Achim G

2018-05-24

Only about 8% of head and neck tumors affect the midface. This anatomical area is characterized by an enormous number of functionally important structures, and it is frequently only possible to achieve small resection margin distances. To avoid complications and unfavorable results, a dedicated preparation of both patient and surgeon is warranted. This review aims to provide encouragement for the postgraduate training of interested ENT specialists. Following the clinical course and based on recent literature, strategies to avoid complications of tumor surgery to the midface are given.

Using the time-to-event continual reassessment method in the presence of partial orders

PubMed Central

Wages, Nolan A.; Conaway, Mark R.; O'Quigley, John

2012-01-01

The time-to-event continual reassessment method (TITE-CRM) was proposed to handle the problem of long trial duration in Phase 1 trials as a result of late-onset toxicities. Here, we implement the TITE-CRM in dose–finding trials of combinations of agents. When studying multiple agents, monotonicity of the dose-toxicity curve is not clearly defined. Therefore, the toxicity probabilities follow a partial order, meaning that there are pairs of treatments for which the ordering of the toxicity probabilities is not known at the start of the trial. A CRM design for partially ordered trials (PO-CRM) was recently proposed. Simulation studies show that extending the TITE-CRM to the partial order setting produces results similar to those of the PO-CRM in terms of maximum tolerated dose recommendation yet reduces the duration of the trial. PMID:22806898

Segregating Variation in the Polycomb Group Gene cramped Alters the Effect of Temperature on Multiple Traits

PubMed Central

Gibert, Jean-Michel; Karch, François; Schlötterer, Christian

2011-01-01

The phenotype produced by a given genotype can be strongly modulated by environmental conditions. Therefore, natural populations continuously adapt to environment heterogeneity to maintain optimal phenotypes. It generates a high genetic variation in environment-sensitive gene networks, which is thought to facilitate evolution. Here we analyze the chromatin regulator crm, identified as a candidate for adaptation of Drosophila melanogaster to northern latitudes. We show that crm contributes to environmental canalization. In particular, crm modulates the effect of temperature on a genomic region encoding Hedgehog and Wingless signaling effectors. crm affects this region through both constitutive heterochromatin and Polycomb silencing. Furthermore, we show that crm European and African natural variants shift the reaction norms of plastic traits. Interestingly, traits modulated by crm natural variants can differ markedly between Drosophila species, suggesting that temperature adaptation facilitates their evolution. PMID:21283785

Evaluating multidisciplinary health care teams: taking the crisis out of CRM.

PubMed

Sutton, Gigi

2009-08-01

High-reliability organisations are those, such as within the aviation industry, which operate in complex, hazardous environments and yet despite this are able to balance safety and effectiveness. Crew resource management (CRM) training is used to improve the non-technical skills of aviation crews and other high-reliability teams. To date, CRM within the health sector has been restricted to use with "crisis teams" and "crisis events". The purpose of this discussion paper is to examine the application of CRM to acute, ward-based multidisciplinary health care teams and more broadly to argue for the repositioning of health-based CRM to address effective everyday function, of which "crisis events" form just one part. It is argued that CRM methodology could be applied to evaluate ward-based health care teams and design non-technical skills training to increase their efficacy, promote better patient outcomes, and facilitate a range of positive personal and organisational level outcomes.

The production and certification of a plutonium equal-atom reference material: NBL CRM 128

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

Crawford, D.W.; Gradle, C.G.; Soriano, M.D.

This report describes the design, production, and certification of the New Brunswick Laboratory plutonium equal-atom certified reference material (CRM), NBL CRM 128. The primary use of this CRM is for the determination of bias corrections encountered in the operation of a mass spectrometer. This reference material is available to the US Department of Energy contractor-operated and government-operated laboratories, as well as to the international nuclear safeguards community. The absolute, or unbiased, certified value for the CRM's Pu-242/Pu-239 ratio is 1.00063 {plus minus} 0.00026 (95% confidence interval) as of October 1, 1984. This value was obtained through the quantitative blending ofmore » high-purity, chemically and isotopically characterized separated isotopes, as well as through intercomparisons of CRM samples with calibration mixtures using thermal ionization mass spectrometry. 32 tabs.« less

Robot-Assisted Versus Open Liver Resection in the Right Posterior Section

PubMed Central

Cipriani, Federica; Ratti, Francesca; Bartoli, Alberto; Ceccarelli, Graziano; Casciola, Luciano; Aldrighetti, Luca

2014-01-01

Background: Open liver resection is the current standard of care for lesions in the right posterior liver section. The objective of this study was to determine the safety of robot-assisted liver resection for lesions located in segments 6 and 7 in comparison with open surgery. Methods: Demographics, comorbidities, clinicopathologic characteristics, surgical treatments, and outcomes from patients who underwent open and robot-assisted liver resection at 2 centers for lesions in the right posterior section between January 2007 and June 2012 were reviewed. A 1:3 matched analysis was performed by individually matching patients in the robotic cohort to patients in the open cohort on the basis of demographics, comorbidities, performance status, tumor stage, and location. Results: Matched patients undergoing robotic and open liver resections displayed no significant differences in postoperative outcomes as measured by blood loss, transfusion rate, hospital stay, overall complication rate (15.8% vs 13%), R0 negative margin rate, and mortality. Patients undergoing robotic liver surgery had significantly longer operative time (mean, 303 vs 233 minutes) and inflow occlusion time (mean, 75 vs 29 minutes) compared with their open counterparts. Conclusions: Robotic and open liver resections in the right posterior section display similar safety and feasibility. PMID:25516700

Resection and drainage of hilar cholangiocarcinoma: an 11-year experience of a single center in mainland China.

PubMed

Zheng-Rong, Lian; Hai-Bo, You; Xin, Chen; Chuan-Xin, Wu; Zuo-Jin, Liu; Bing, Tu; Jian-Ping, Gong; Sheng-Wei, Li

2011-05-01

The purpose of this study is to provide appropriate approaches for resection and drainage of hilar cholangiocarcinomas. Surgical approaches and postoperative survival rates of the patients were analyzed retrospectively. The 1-, 3-, and 5-year cumulative survival rates for patients who underwent resection were 76.6, 36.2, and 10.6 per cent, which was higher than those of 60, 14.3, and 0 per cent, respectively, in palliative operation. Moreover, the 1-, 3-, and 5-year cumulative survival rates for patients who underwent R0 were 88.9, 44.4, and 13.9 per cent, which was improved compared with those of 36.4, 9.1, and 0 per cent, respectively, in nonR0 resection. In addition, the overall survival time of patients who underwent R0 resection combined with hemihepatectomy and caudate lobe resection was longer than of those who underwent R0 without this extra operation, especially within 3 years after operation. After endoscopic metal biliary endoprothesis for patients who were intolerant of resection, liver function was improved at 2 weeks postoperation and the 1-, 3-, and 5-year cumulative survival rates for these patients were 72.7, 18.2, and 0 per cent, respectively. Treatment should be personalized. Resection is the most efficacious therapy, and negative histologic margins should be achieved in radical operation and "skeletonized" surgical operation is the basic requirement of radical treatment of hilar cholangiocarcinoma. Portal vein resection is beneficial to long-term survival and R0 resection combined with caudate lobe resection and hemihepatectomy is more efficacious for patients with Bismuth-Corlette type III hilar cholangiocarcinoma. The preferred approach of drainage in palliative operation is endoscopic metal biliary endoprothesis, which is more appropriate than tumor resection for the patients who suffer from serious comorbidities.

A technique for laparoendoscopic resection of posterior fundic gastric GISTs without need for a gastrotomy.

PubMed

Maker, Ajay V

2013-12-01

The majority of gastrointestinal stromal tumors (GISTs) are located in the stomach. With greater experience in minimally invasive oncologic surgery, gastric GISTs are being increasingly approached laparoscopically. Posterior proximally located endophytic gastric GISTs can be challenging to approach laparoscopically and excise with an adequate margin without an anterior or posterior gastrotomy, or intragastric ports. The gastrocolic and gastrosplenic ligaments are divided up to the gastroesophageal junction. The left lateral segment of the liver is mobilized to allow anterior reflection of the gastric fundus. Intraoperative ultrasound confirms the location and extent of the tumor base. Upper endoscopy is performed to trans-illuminate, confirm tumor location, and search for multifocality. Traction sutures are placed around the tumor to distract endophytic lesions. With organo-axial rotation of the stomach using the stay sutures, an endoGIA stapler approximates the posterior fundic wall under the base of the lesion ensuring an adequate margin and eliminating the risk of gastric spillage. Appropriate stapler placement and margins are assisted real-time endoscopically with picture-in-picture. The stapleline is tested for leaks and inspected for hemostasis laparoendoscopically. Complete resection of GISTs with adequate margins is performed with sound oncologic principles and demonstrated in tumors of varying sizes and locations in the proximal posterior stomach, including near the GE junction. This video demonstrates a simple laparoendoscopic technique to quickly localize even small tumors, visually confirm adequate margins, and excise gastric GISTs without spillage or gastrotomy that are located in a typically difficult area of the stomach to approach laparoscopically.

Role of Adjuvant Therapy for Node-Negative Lung Cancer Invading the Chest Wall.

PubMed

Gao, Sarah J; Corso, Christopher D; Blasberg, Justin D; Detterbeck, Frank C; Boffa, Daniel J; Decker, Roy H; Kim, Anthony W

2017-03-01

The present study investigated the effect of adjuvant chemotherapy and radiation on survival among patients undergoing chest wall resection for T3N0 non-small cell lung cancer (NSCLC). Patients with T3N0 NSCLC who underwent chest wall resection were identified in the National Cancer Data Base in 2004 to 2012. The cohort was divided into patients who had received adjuvant chemotherapy, radiation therapy, chemoradiation therapy, or no adjuvant treatment. Kaplan-Meier and log-rank tests were used to compare overall survival, and a bootstrapped Cox proportional hazards model was used to determine the significant contributors to survival. A subset analysis was performed with stratification by margin status and tumor size. Of 759 patients identified, 42.0% underwent surgery alone, 23.3% underwent surgery followed by chemotherapy, 22.3% underwent surgery followed by chemoradiation therapy, and 12.3% underwent surgery followed by radiotherapy alone. Tumors > 4 cm benefited from adjuvant chemotherapy and radiation therapy in the multivariable analysis, and those ≤ 4 cm benefited only from adjuvant chemotherapy. The subgroup analysis by margin status identified that margin-positive patients with tumors > 4 cm benefited significantly from either adjuvant chemoradiation therapy or radiation therapy alone. T3N0 NSCLC with chest wall invasion requires unique management compared with other stage IIB tumors. An important determinant of management is tumor size, with tumors ≤ 4 cm benefiting from adjuvant chemotherapy and tumors > 4 cm benefiting from adjuvant chemotherapy if margin negative and adjuvant chemoradiation therapy or radiotherapy if margin positive. Copyright © 2016 Elsevier Inc. All rights reserved.

Should spikes on post-resection ECoG guide pediatric epilepsy surgery?

PubMed

Greiner, Hansel M; Horn, Paul S; Tenney, Jeffrey R; Arya, Ravindra; Jain, Sejal V; Holland, Katherine D; Leach, James L; Miles, Lili; Rose, Douglas F; Fujiwara, Hisako; Mangano, Francesco T

2016-05-01

There is wide variation in clinical practice regarding the role of electrocorticography immediately after resection (post-resection ECoG) for pediatric epilepsy surgery. Results can guide further resection of potentially epileptogenic tissue. We hypothesized that post-resection ECoG spiking represents a biomarker of the epileptogenic zone and predicts seizure outcome in children undergoing epilepsy surgery. We retrospectively identified 124 children with post-resection ECoG performed on the margins of resection. ECoG records were scored in a blinded fashion based on presence of frequent spiking. For patients identified as having additional resection based on clinical post-resection ECoG interpretation, these "second-look" ECoG results were re-reviewed for ongoing discharges or completeness of resection. Frequent spike populations were grouped using a standard scoring system into three ranges: 0.1-0.5Hz, 0.5-1Hz, >1Hz. Seizure outcomes were determined at minimum 12-month followup. Of 124 patients who met inclusion criteria, 60 (48%) had an identified spike population on post-resection ECoG. Thirty (50%) of these had further resection based on clinical interpretation. Overall, good outcome (ILAE 1) was seen in 56/124 (45%). Completeness of resection of spiking (absence of spiking on initial post-resection ECoG or resolution of spiking after further resection) showed a trend toward good outcome (OR 2.03, p=0.099). Patients with completeness of resection had good outcome in 41/80 (51%) of cases; patients with continued spikes had good outcome in 15/44 (35%) of cases. Post-resection ECoG identifies residual epileptogenic tissue in a significant number of children. Lower frequency or absence of discharges on initial recording showed a trend toward good outcome. Completeness of resection demonstrated on final ECoG recording did not show a significant difference in outcome. This suggests that post-resection discharges represent a prognostic marker rather than a remediable biomarker of the epileptogenic zone in all patients. Resecting residual spike-generating cortex may be beneficial in selected patients, including children with tumors. Copyright © 2016 Elsevier B.V. All rights reserved.

Transfer of learning and patient outcome in simulated crisis resource management: a systematic review.

PubMed

Boet, Sylvain; Bould, M Dylan; Fung, Lillia; Qosa, Haytham; Perrier, Laure; Tavares, Walter; Reeves, Scott; Tricco, Andrea C

2014-06-01

Simulation-based learning is increasingly used by healthcare professionals as a safe method to learn and practice non-technical skills, such as communication and leadership, required for effective crisis resource management (CRM). This systematic review was conducted to gain a better understanding of the impact of simulation-based CRM teaching on transfer of learning to the workplace and subsequent changes in patient outcomes. Studies on CRM, crisis management, crew resource management, teamwork, and simulation published up to September 2012 were searched in MEDLINE(®), EMBASE™, CINAHL, Cochrane Central Register of Controlled Trials, and ERIC. All studies that used simulation-based CRM teaching with outcomes measured at Kirkpatrick Level 3 (transfer of learning to the workplace) or 4 (patient outcome) were included. Studies measuring only learners' reactions or simple learning (Kirkpatrick Level 1 or 2, respectively) were excluded. Two authors independently reviewed all identified titles and abstracts for eligibility. Nine articles were identified as meeting the inclusion criteria. Four studies measured transfer of simulation-based CRM learning into the clinical setting (Kirkpatrick Level 3). In three of these studies, simulation-enhanced CRM training was found significantly more effective than no intervention or didactic teaching. Five studies measured patient outcomes (Kirkpatrick Level 4). Only one of these studies found that simulation-based CRM training made a clearly significant impact on patient mortality. Based on a small number of studies, this systematic review found that CRM skills learned at the simulation centre are transferred to clinical settings, and the acquired CRM skills may translate to improved patient outcomes, including a decrease in mortality.

CRM done right.

PubMed

Rigby, Darrell K; Ledingham, Dianne

2004-11-01

Disappointed by the high costs and elusive benefits, early adopters of customer relationship management systems came, in the post dot-com era, to view the technology as just another overhyped IT investment whose initial promise would never be fulfilled. But this year, something unexpected is happening. System sales are rising, and executives are reporting satisfaction with their CRM investments. What's changed? A wide range of companies are successfully taking a pragmatic, disciplined approach to CRM. Rather than use it to transform entire businesses, they've directed their investments toward solving clearly defined problems within their customer relationship cycle. The authors have distilled the experiences of these CRM leaders into four questions that all companies should ask themselves as they launch their own CRM initiatives: Is the problem strategic? Is the system focused on the pain point? Do we need perfect data? What's the right way to expand an initial implementation? The questions reflect a new realism about when and how to deploy CRM to best advantage. Understanding that highly accurate and timely data are not required everywhere in their businesses, CRM leaders have tailored their real-time initiatives to those customer relationships that can be significantly enhanced by "perfect" information. Once they've succeeded with their first targeted CRM project, they can use it as a springboard for solving additional problems. CRM, in other words, is coming to resemble any other valuable management tool, and the keys to successful implementation are also becoming familiar: strong executive and business-unit leadership, careful strategic planning, clear performance measures, and a coordinated program that combines organizational and process changes with the application of new technology.

Inhibition of CRM1-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents

PubMed Central

Turner, Joel G.; Dawson, Jana; Cubitt, Christopher L.; Baz, Rachid; Sullivan, Daniel M.

2014-01-01

Nuclear-cytoplasmic trafficking of proteins is a significant factor in the development of cancer and drug resistance. Subcellular localization of exported proteins linked to cancer development include those involved in cell growth and proliferation, apoptosis, cell cycle regulation, transformation, angiogenesis, cell adhesion, invasion, and metastasis. Here, we examined the basic mechanisms involved in the export of proteins from the nucleus to the cytoplasm. All proteins over 40 kDa use the nuclear pore complex to gain entry or exit from the nucleus, with the primary nuclear export molecule involved in these processes being chromosome region maintenance 1 (CRM1, exportin 1 or XPO1). Proteins exported from the nucleus must possess a hydrophobic nuclear export signal (NES) peptide that binds to a hydrophobic groove containing an active-site Cys528 in the CRM1 protein. CRM1 inhibitors function largely by covalent modification of the active site Cys528 and prevent binding to the cargo protein NES. In the absence of a CRM1 inhibitor, CRM1 binds cooperatively to the NES of the cargo protein and RanGTP, forming a trimer that is actively transported out of the nucleus by facilitated diffusion. Nuclear export can be blocked by CRM1 inhibitors, NES peptide inhibitors or by preventing post-translational modification of cargo proteins. Clinical trials using the classic CRM1 inhibitor leptomycin B proved too toxic for patients; however, a new generation of less toxic small molecule inhibitors are being used in clinical trials in patients with both hematological malignancies and solid tumors. Additional trials are being initiated using small-molecule CRM1 inhibitors in combination with chemotherapeutics such as pegylated liposomal doxorubicin. In this review, we present evidence that combining the new CRM1 inhibitors with other classes of therapeutics may prove effective in the treatment of cancer. Potential combinatorial therapies discussed include the use of CRM1 inhibitors and the addition of alkylating agents (melphalan), anthracyclines (doxorubicin and daunomycin), BRAF inhibitors, platinum drugs (cisplatin and oxaliplatin), proteosome inhibitors (bortezomib and carfilzomib), or tyrosine-kinase inhibitors (imatinib). Also, the sequence of treatment may be important for combination therapy. We found that the most effective treatment regimen involved first priming the cancer cells with the CRM1 inhibitor followed by doxorubicin, bortezomib, carfilzomib, or melphalan. This order sensitized both de novo and acquired drug-resistant cancer cell lines. PMID:24631834

Immunogenicity and safety of concomitant administration of a combined hepatitis A/B vaccine and a quadrivalent meningococcal conjugate vaccine in healthy adults.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil C; Meyer, Seetha; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani Kumar

2015-01-01

This phase 3b randomized, open-label study evaluated the immunogenicity and safety of coadministration of a hepatitis A and/or B vaccine with a quadrivalent oligosaccharide meningococcal CRM197 -conjugate vaccine (MenACWY-CRM), in the context of an accelerated hepatitis A and/or B immunization schedule. A total of 252 healthy adult subjects were randomized to three groups to receive hepatitis A/B only (HepA/B), hepatitis A/B coadministered with MenACWY-CRM (HepA/B+MenACWY-CRM), or MenACWY-CRM only (MenACWY-CRM). Hepatitis A and/or B vaccination was administered in the form of a single booster dose or a primary three-dose series, depending on the hepatitis A and/or B vaccination history of subjects. Antibody responses to hepatitis A/B vaccination were assessed 1 month following the last hepatitis A and/or B dose. Serum bactericidal activity with human complement (hSBA) against meningococcal serogroups A, C, W-135, and Y was assessed 1 month post-MenACWY-CRM vaccination. Safety was monitored throughout the study. At 1 month following the final hepatitis A and/or B vaccination, concomitant administration of hepatitis A/B and MenACWY-CRM was non-inferior to administration of hepatitis A/B alone in terms of geometric mean concentrations of antibodies against the hepatitis A and B antigens. One month post-MenACWY-CRM vaccination, the percentages of subjects achieving hSBA titers ≥8 for serogroups A, C, W-135, and Y in the HepA/B+MenACWY-CRM group (76, 87, 99, and 94%, respectively) were comparable to those in the MenACWY-CRM group (67, 82, 96, and 88%, respectively). The percentages of subjects reporting adverse events (AEs) were similar across study groups and a majority of the reported AEs were mild to moderate in nature. There were no study vaccine-related serious AEs. MenACWY-CRM can be administered concomitantly with a hepatitis A and/or B vaccine in the context of an accelerated hepatitis A and/or B immunization schedule without increasing safety concerns or compromising the immune responses to any of the vaccine antigens. [NCT01453348]. © 2014 International Society of Travel Medicine.

Recurrent subcutaneous trunk leiomyosarcoma: Management and review of the literature.

PubMed

Salemis, Nikolaos S

2013-01-01

Superficial leiomyosarcomas are rare malignant smooth-muscle tumors accounting for 4-6.5% of all soft-tissue sarcomas, less than 2-3% of cutaneous soft-tissue neoplasms and 0.04% of all cancers. They are divided into cutaneous or dermal and subcutaneous leiomyosarcomas. Subcutaneous tumors have been reported to be associated with an increased risk of local recurrences and distant metastases, compared to their cutaneous counterparts. In this study, we describe a rare case of a recurrent subcutaneous trunk leiomyosarcoma in a 68-year-old male patient. Local recurrence developed two years after the complete surgical resection with wide margins and adjuvant postoperative radiotherapy. The management of the patient is discussed along with a review of the literature. We conclude that subcutaneous leiomyosarcoma is a rare clinical entity which may be associated with an atypical clinical presentation. Physicians should be aware of the misleading features of this tumor in order to avoid delay in diagnosis and treatment. Early complete surgical resection with wide margins of at least 2 cm is the cornerstone of treatment and has been reported to mostly influence the prognosis. However, the tumor has a high tendency to recur locally and metastasize. Recurrence may develop despite wide resection and radiotherapy. Long-term follow-up is mandatory.

Recurrent subcutaneous trunk leiomyosarcoma: Management and review of the literature

PubMed Central

Salemis, Nikolaos S.

2013-01-01

Superficial leiomyosarcomas are rare malignant smooth-muscle tumors accounting for 4-6.5% of all soft-tissue sarcomas, less than 2-3% of cutaneous soft-tissue neoplasms and 0.04% of all cancers. They are divided into cutaneous or dermal and subcutaneous leiomyosarcomas. Subcutaneous tumors have been reported to be associated with an increased risk of local recurrences and distant metastases, compared to their cutaneous counterparts. In this study, we describe a rare case of a recurrent subcutaneous trunk leiomyosarcoma in a 68-year-old male patient. Local recurrence developed two years after the complete surgical resection with wide margins and adjuvant postoperative radiotherapy. The management of the patient is discussed along with a review of the literature. We conclude that subcutaneous leiomyosarcoma is a rare clinical entity which may be associated with an atypical clinical presentation. Physicians should be aware of the misleading features of this tumor in order to avoid delay in diagnosis and treatment. Early complete surgical resection with wide margins of at least 2 cm is the cornerstone of treatment and has been reported to mostly influence the prognosis. However, the tumor has a high tendency to recur locally and metastasize. Recurrence may develop despite wide resection and radiotherapy. Long-term follow-up is mandatory. PMID:23633873

["In-situ split" (ISS) liver resection: new aspects of technique and indication].

PubMed

Lang, S A; Loss, M; Schlitt, H J

2014-04-01

The combination of right portal vein ligation with complete parenchyma dissection ("in-situ split", ISS) for rapid hypertrophy induction of the left-lateral liver lobe is a novel strategy to convert primarily irresectable liver tumours into a resectable stage. Available data so far show a 60-80 % growth induction of the remnant liver within 7(- 9) days. Certainly, a novel concept that comprises two operations within a very short time period raises questions. Based on the very few literature reports that have been published so far, as well as our own experience, we here discuss technical issues such as the use of a plastic sheet on the resection margin, the possibility of laparoscopic dissection and the timing of the second operation. Moreover, aspects of the preoperative diagnostic work-up that is necessary are assessed. Finally, open questions, e.g., concerning the influence of preoperative chemotherapy and the use of ISS in patients with cirrhosis are evaluated. In summary, the assessment of chances and risks of this novel concept with regard to indication and technical issues helps to provide the potentially curative option of the "in-situ split" procedure to more patients with marginal or even irresectable liver tumours. Georg Thieme Verlag KG Stuttgart · New York.

Characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver: A report from the National Cancer Database.

PubMed

Shi, Yan; Rojas, Yesenia; Zhang, Wei; Beierle, Elizabeth A; Doski, John J; Goldfarb, Melanie; Goldin, Adam B; Gow, Kenneth W; Langer, Monica; Meyers, Rebecka L; Nuchtern, Jed G; Vasudevan, Sanjeev A

2017-04-01

To examine patient characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver (UESL) using a multi-institutional database. UESL is a rare disease (incidence is one per million). Therefore, the current literature is mostly limited to small case series. The National Cancer Database was queried for primary UESL diagnosed between 1998 and 2012. A total of 103 patients (<18 years) were identified. The 5-year overall survival of the entire group was 86%. The best outcomes were seen in children who had tumors smaller than 15 cm and were able to undergo surgical resection with or without chemotherapy. Margin status did not appear to significantly affect survival. The most common type of resection was hemihepatectomy (37%), followed by sectionectomy (10%) and trisectionectomy (10%). Orthotopic liver transplant was performed in 10 children, all of whom survived to 5 years. Surgical resection with or without chemotherapy should be the mainstay of treatment in children with UESL, and is associated with very favorable outcomes. Negative surgical margins were not associated with improved survival. Orthotopic liver transplantation may be a viable method of attaining local control in tumors, which would otherwise be unresectable. © 2016 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

Characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver: A report from the National Cancer Database

PubMed Central

Shi, Yan; Rojas, Yesenia; Zhang, Wei; Beierle, Elizabeth A.; Doski, John J.; Goldfarb, Melanie; Goldin, Adam B.; Gow, Kenneth W.; Langer, Monica; Meyers, Rebecka L.; Nuchtern, Jed G.

2016-01-01

Abstract Objective To examine patient characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver (UESL) using a multi‐institutional database. Summary Background Data UESL is a rare disease (incidence is one per million). Therefore, the current literature is mostly limited to small case series. Methods The National Cancer Database was queried for primary UESL diagnosed between 1998 and 2012. Results A total of 103 patients (<18 years) were identified. The 5‐year overall survival of the entire group was 86%. The best outcomes were seen in children who had tumors smaller than 15 cm and were able to undergo surgical resection with or without chemotherapy. Margin status did not appear to significantly affect survival. The most common type of resection was hemihepatectomy (37%), followed by sectionectomy (10%) and trisectionectomy (10%). Orthotopic liver transplant was performed in 10 children, all of whom survived to 5 years. Conclusion Surgical resection with or without chemotherapy should be the mainstay of treatment in children with UESL, and is associated with very favorable outcomes. Negative surgical margins were not associated with improved survival. Orthotopic liver transplantation may be a viable method of attaining local control in tumors, which would otherwise be unresectable. PMID:27781381

An allele of the crm gene blocks cyanobacterial circadian rhythms.

PubMed

Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

2013-08-20

The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA.

The effects of Crew Resource Management (CRM) training on flight attendants' safety attitudes.

PubMed

Ford, Jane; Henderson, Robert; O'Hare, David

2014-02-01

A number of well-known incidents and accidents had led the aviation industry to introduce Crew Resource Management (CRM) training designed specifically for flight attendants, and joint (pilot and flight attendant) CRM training as a way to improve teamwork and communication. The development of these new CRM training programs during the 1990s highlighted the growing need for programs to be evaluated using research tools that had been validated for the flight attendant population. The FSAQ (Flight Safety Attitudes Questionnaire-Flight Attendants) was designed specifically to obtain safety attitude data from flight attendants working for an Asia-Pacific airline. Flight attendants volunteered to participate in a study before receiving CRM training (N=563) and again (N=526) after CRM training. Almost half (13) of the items from the 36-item FSAQ showed highly significant changes following CRM training. Years of experience, crew position, seniority, leadership roles, flight attendant crew size, and length of route flown were all predictive of safety attitudes. CRM training for flight attendants is a valuable tool for increasing positive teamwork behaviors between the flight attendant and pilot sub-groups. Joint training sessions, where flight attendants and pilots work together to find solutions to in-flight emergency scenarios, provide a particularly useful strategy in breaking down communication barriers between the two sub-groups. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

Human error and crew resource management failures in Naval aviation mishaps: a review of U.S. Naval Safety Center data, 1990-96.

PubMed

Wiegmann, D A; Shappell, S A

1999-12-01

The present study examined the role of human error and crew-resource management (CRM) failures in U.S. Naval aviation mishaps. All tactical jet (TACAIR) and rotary wing Class A flight mishaps between fiscal years 1990-1996 were reviewed. Results indicated that over 75% of both TACAIR and rotary wing mishaps were attributable, at least in part, to some form of human error of which 70% were associated with aircrew human factors. Of these aircrew-related mishaps, approximately 56% involved at least one CRM failure. These percentages are very similar to those observed prior to the implementation of aircrew coordination training (ACT) in the fleet, suggesting that the initial benefits of the program have not persisted and that CRM failures continue to plague Naval aviation. Closer examination of these CRM-related mishaps suggest that the type of flight operations (preflight, routine, emergency) do play a role in the etiology of CRM failures. A larger percentage of CRM failures occurred during non-routine or extremis flight situations when TACAIR mishaps were considered. In contrast, a larger percentage of rotary wing CRM mishaps involved failures that occurred during routine flight operations. These findings illustrate the complex etiology of CRM failures within Naval aviation and support the need for ACT programs tailored to the unique problems faced by specific communities in the fleet.

Petrosectomies for invasive tumours: surgery and reconstruction.

PubMed

Malata, C M; Cooter, R D; Towns, G M; Batchelor, A G

1996-09-01

Tumours involving the temporal bone have historically carried a bad prognosis. The only prospect of cure is radical en bloc resection. Temporal bone resection for malignancies is, however, such a formidable undertaking that many centres label such tumours as unresectable. Additionally, the enormity of the surgical defect poses a major reconstructive challenge. A review of 14 petrosectomies (in 12 males and 2 females) performed for extensively invasive neoplasms in and around the ear is presented. All underwent immediate reconstruction, the majority (12/14) with free tissue transfers. 9 of the 14 patients (64%) are still alive after a mean follow-up of 70 months (range 4-8 years). With the use of free tissue transfers, an aggressive approach with regard to the resection margins can safely be adopted in the full knowledge that the eventual size of the defect need not compromise tumour clearance. Additionally, free flaps provided a reliable dural seal. This approach of radical en bloc resection with free flap reconstruction has decreased the mortality (compared to the literature), while largely reducing the morbidity to that of unavoidable cranial nerve resection.

Repeat liver resection for recurrent colorectal metastases: a single-centre, 13-year experience.

PubMed

Battula, Narendra; Tsapralis, Dimitrios; Mayer, David; Isaac, John; Muiesan, Paolo; Sutcliffe, Robert P; Bramhall, Simon; Mirza, Darius; Marudanayagam, Ravi

2014-02-01

Isolated intrahepatic recurrence is noted in up to 40% of patients following curative liver resection for colorectal liver metastases (CLM). The aims of this study were to analyse the outcomes of repeat hepatectomy for recurrent CLM and to identify factors predicting survival. Data for all liver resections for CLM carried out at one centre between 1998 and 2011 were analysed. A total of 1027 liver resections were performed for CLM. Of these, 58 were repeat liver resections performed in 53 patients. Median time intervals were 10.5 months between the primary resection and first hepatectomy, and 15.4 months between the first and repeat hepatectomies. The median tumour size was 3.0 cm and the median number of tumours was one. Six patients had a positive margin (R1) resection following first hepatectomy. There were no perioperative deaths. Significant complications included transient liver dysfunction in one and bile leak in two patients. Rates of 1-, 3- and 5-year overall survival following repeat liver resection were 85%, 61% and 52%, respectively, at a median follow-up of 23 months. R1 resection at first hepatectomy (P = 0.002), a shorter time interval between the first and second hepatectomies (P = 0.02) and the presence of extrahepatic disease (P = 0.02) were associated with significantly worse overall survival. Repeat resection of CLM is safe and can achieve longterm survival in carefully selected patients. A preoperative knowledge of poor prognostic factors helps to facilitate better patient selection. © 2013 International Hepato-Pancreato-Biliary Association.

Laparoscopic liver resection: Experience based guidelines

PubMed Central

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

2016-01-01

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. PMID:26843910

Use of simplifier scenarios for CRM training

NASA Technical Reports Server (NTRS)

Weatherly, D.

1984-01-01

Cockpit resource management (CRM) at Metro Airlines is discussed. The process by which the program of CRM training was initiated is mentioned. Management aspects of various flying scenarios are considered. The transfer of training from the classroom to the field is assessed.

Matrix solid phase dispersion-assisted BCR sequential extraction method for metal partitioning in surface estuarine sediments.

PubMed

Martínez-Fernández, Marta; Barciela-Alonso, María Carmen; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar

2011-01-15

The BCR (the Community Bureau of Reference) of the European Union sequential extraction scheme for metal partitioning in estuarine sediments has been accelerated by using a matrix solid phase dispersion (MSPD) approach. The MSPD assisted BCR procedure consists of passing the extractants proposed by conventional BCR protocol (0.11 M acetic acid, 0.1M hydroxylammonium chloride and 8.8M hydrogen peroxide plus 1M ammonium acetate) through the dispersed sample packaged inside a disposable syringe. Different silica-, magnesium- and aluminium-based materials were tested as dispersing agents and sea sand was found to offer the best performances. Variables for assisting the three stages of the BCR protocol were optimized, and accurate results were obtained when assisting the first and the third stages (exchangeable and oxidizable fractions, respectively). However, lack of accuracy was observed when assisting the second step (reducible fraction) and this result agrees with most of the assisted BCR procedures for which extracting the reducible fraction is the most troublesome stage. The organic matter oxidation (third stage) was successfully assisted by passing hydrogen peroxide at 50°C through the dispersed sample inside de syringe just before passing ammonium acetate. Therefore, the time-consuming and unsafe conventional organic matter oxidation processes, commonly performed even for microwave/ultrasounds assisted BCR procedures, are totally avoided. Inductively coupled plasma-mass spectrometry (ICP-MS) was used as a selective detector. The target elements were Cd, Co, Cr, Mn, Ni, Sr and Zn (first stage), Cd, Co and Ni (second stage), and Co, Cr, Mn, Ni, Sr and Zn (third stage). Repeatability of the method (n=7) was good, and RSDs values of 9, 10, 10, 8, 8, 3 and 8% was obtained for Cd, Co, Cr, Mn, Ni, Sr and Zn, respectively (first stage); 10, 9 and 9% for Cd, Co and Ni, respectively (second stage); and 6, 2, 3, 4, 7 and 9% Co, Cr, Mn, Ni, Sr and Zn, respectively (third stage). The procedure was also validated by analysing two certified reference materials (CRM 601 and CRM 701). Good accuracy was obtained for the target elements extracted at the first stage: Cd (4.0 ± 0.1 and 7.3 ± 0.09 μg g(-1) in CRM 601 and CRM 701, respectively), Cr (0.36 ± 0.008 and 2.21 ± 0.08 μg g(-1) in CRM 601 and CRM 701, respectively), Ni (8.0 ± 0.3 and 15.4 ± 0.3 μg g(-1) in CRM 601 and CRM 701, respectively) and Zn (262 ± 3 and 203 ± 3 μg g(-1) in CRM 601 and CRM 701, respectively). Also, good accuracy was observed for elements extracted at the third step: Cd (1.8 ± 0.09 and 0.29 ± 0.03 μg g(-1) in CRM 601 and CRM 701, respectively), Cr (145 ± 4 μg g(-1) in CRM 701), Ni (8.2 ± 0.7 and 15.1 ± 0.5 μg g(-1) in CRM 601 and CRM 701, respectively) and Zn (45 ± 0.7 μg g(-1) in CRM 701). Copyright © 2010 Elsevier B.V. All rights reserved.

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

Tang, Xiao-han; Deng, Suo; Li, Meng

Highlights: Black-Right-Pointing-Pointer HB-EGF over-expression in A2780/Taxol, A2780/CDDP cells and the matched xenografts. Black-Right-Pointing-Pointer CRM197 induces enhanced apoptosis in A2780/Taxol and A2780/CDDP cells. Black-Right-Pointing-Pointer CRM197 arrests A2780/Taxol and A2780/CDDP cells at G0/G1 phase. Black-Right-Pointing-Pointer CRM197 suppressed the A2780/Taxol and A2780/CDDP growth of xenografts. -- Abstract: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. Cross-reacting material 197 (CRM197), a specific HB-EGF inhibitor, has been proven to represent possible chemotherapeutic agent for ovarian cancer. However, the effect of CRM197 on the resistant ovarian carcinoma cells has not been sufficiently elucidated. Here, we found that HB-EGF wasmore » over-expressed in a paclitaxel-resistant human ovarian carcinoma cell line (A2780/Taxol) and a cisplatin-resistant cell line (A2780/CDDP), as well as the xenograft mouse tissue samples with these cells. To investigate the possible significance of the HB-EGF over-expression in A2780/Taxol and A2780/CDDP cells, we inhibited HB-EGF expression by CRM197 to investigate the effect of CRM197 treatment on these cells. We observed that CRM197 significantly induced anti-proliferative activity in a dose-dependent manner with the cell-cycle arrest at the G0/G1 phase and enhanced apoptosis in A2780/Taxol and A2780/CDDP cells. The sensitive ovarian carcinoma parental cell line (A2780), A2780/Taxol and A2780/CDDP cells formed tumors in nude mice, and enhanced tumorigenicity was observed in drug-resistant tumors. Furthermore, we observed that CRM197 significantly suppressed the growth of drug-resistant ovarian cancer xenografts in vivo (p < 0.001). These results suggest that CRM197 as an HB-EGF-targeted agent has potent anti-tumor activity in paclitaxel- and cisplatin-resistant ovarian cancer which over-express HB-EGF.« less

Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.

PubMed

Reisinger, Keith S; Baxter, Roger; Block, Stanley L; Shah, Jina; Bedell, Lisa; Dull, Peter M

2009-12-01

Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals > or = 15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of > or = 1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than -10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra.

Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population

PubMed Central

Apland, James P.; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Pidoplichko, Volodymyr I.; Rossetti, Katia

2018-01-01

The currently Food and Drug Administration–approved anticonvulsant for the treatment of status epilepticus (SE) induced by nerve agents is the benzodiazepine diazepam; however, diazepam does not appear to offer neuroprotective benefits. This is of particular concern with respect to the protection of children because, in the developing brain, synaptic transmission mediated via GABAA receptors, the target of diazepam, is weak. In the present study, we exposed 21-day-old male rats to 1.2 × LD50 soman and compared the antiseizure, antilethality, and neuroprotective efficacy of diazepam (10 mg/kg), LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (CRM, an antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and LY293558 (15 mg/kg) + CRM (50 mg/kg), administered 1 hour after exposure. Diazepam, LY293558, and LY293558 + CRM, but not CRM alone, terminated SE; LY293558 + CRM treatment acted significantly faster and produced a survival rate greater than 85%. Thirty days after soman exposure, neurodegeneration in limbic regions was most severe in the CRM-treated group, minimal to severe—depending on the region—in the diazepam group, absent to moderate in the LY293558-treated group, and totally absent in the LY293558 + CRM group. Amygdala and hippocampal atrophy, a severe reduction in spontaneous inhibitory activity in the basolateral amygdala, and increased anxiety-like behavior in the open-field and acoustic startle response tests were present in the diazepam and CRM groups, whereas the LY293558 and LY293558 + CRM groups did not differ from controls. The combined administration of LY293558 and CRM, by blocking mainly AMPA, GluK1, and NMDA receptors, is a very effective anticonvulsant and neuroprotective therapy against soman in young rats. PMID:29467308

Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins.

PubMed

Takeda, Akiko; Sarma, Nayan J; Abdul-Nabi, Anmaar M; Yaseen, Nabeel R

2010-05-21

NUP98 is a nucleoporin that plays complex roles in the nucleocytoplasmic trafficking of macromolecules. Rearrangements of the NUP98 gene in human leukemia result in the expression of numerous fusion oncoproteins whose effect on nucleocytoplasmic trafficking is poorly understood. The present study was undertaken to determine the effects of leukemogenic NUP98 fusion proteins on CRM1-mediated nuclear export. NUP98-HOXA9, a prototypic NUP98 fusion, inhibited the nuclear export of two known CRM1 substrates: mutated cytoplasmic nucleophosmin and HIV-1 Rev. In vitro binding assays revealed that NUP98-HOXA9 binds CRM1 through the FG repeat motif in a Ran-GTP-dependent manner similar to but stronger than the interaction between CRM1 and its export substrates. Two NUP98 fusions, NUP98-HOXA9 and NUP98-DDX10, whose fusion partners are structurally and functionally unrelated, interacted with endogenous CRM1 in myeloid cells as shown by co-immunoprecipitation. These leukemogenic NUP98 fusion proteins interacted with CRM1, Ran, and the nucleoporin NUP214 in a manner fundamentally different from that of wild-type NUP98. NUP98-HOXA9 and NUP98-DDX10 formed characteristic aggregates within the nuclei of a myeloid cell line and primary human CD34+ cells and caused aberrant localization of CRM1 to these aggregates. These NUP98 fusions caused nuclear accumulation of two transcription factors, NFAT and NFkappaB, that are regulated by CRM1-mediated export. The nuclear entrapment of NFAT and NFkappaB correlated with enhanced transcription from promoters responsive to these transcription factors. Taken together, the results suggest a new mechanism by which NUP98 fusions dysregulate transcription and cause leukemia, namely, inhibition of CRM1-mediated nuclear export with aberrant nuclear retention of transcriptional regulators.

THE CIDOC CRM GAME: A Serious Game Approach to Ontology Learning

NASA Astrophysics Data System (ADS)

Guillem, A.; Bruseker, G.

2017-08-01

Formal ontologies such as CIDOC CRM (Conceptual Reference Model) form part of the central strategy for the medium and longterm integration of cultural heritage data to allow for its greater valorization and dissemination. Despite this, uptake of CIDOC CRM at the ground level of Cultural Heriage (CH) practice is limited. Part of the reason behind this lack of uptake lies in the fact that ontologies are considered too complicated and abstract for application in real life scenarios. This paper presents the rationale behind and the design of a CIDOC CRM game, the intent of which is to provide a learning mechanism to allow learners of wide backgrounds and interests to approach CIDOC CRM in a hands-on and interactive fashion. The CIDOC CRM game consist of decks of cards and game boards that allow players to engage with the concepts of a formal ontology in relation to real data in an entertaining and informative way. It is argued that the CIDOC CRM Game can form an important part of introducing the basic elements of formal ontology and this standard to a wider audience in order to aid wider understanding and adoption of the same.

The role of liver-directed surgery in patients with hepatic metastasis from primary breast cancer: a multi-institutional analysis.

PubMed

Margonis, Georgios A; Buettner, Stefan; Sasaki, Kazunari; Kim, Yuhree; Ratti, Francesca; Russolillo, Nadia; Ferrero, Alessandro; Berger, Nickolas; Gamblin, T Clark; Poultsides, George; Tran, Thuy; Postlewait, Lauren M; Maithel, Shishir; Michaels, Alex D; Bauer, Todd W; Marques, Hugo; Barroso, Eduardo; Aldrighetti, Luca; Pawlik, Timothy M

2016-08-01

Data on surgical management of breast liver metastasis are limited. We sought to determine the safety and long-term outcome of patients undergoing hepatic resection of breast cancer liver metastases (BCLM). Using a multi-institutional, international database, 131 patients who underwent surgery for BCLM between 1980 and 2014 were identified. Clinicopathologic and outcome data were collected and analyzed. Median tumor size of the primary breast cancer was 2.5 cm (IQR: 2.0-3.2); 58 (59.8%) patients had primary tumor nodal metastasis. The median time from diagnosis of breast cancer to metastasectomy was 34 months (IQR: 16.8-61.3). The mean size of the largest liver lesion was 3.0 cm (2.0-5.0); half of patients (52.0%) had a solitary metastasis. An R0 resection was achieved in most cases (90.8%). Postoperative morbidity and mortality were 22.8% and 0%, respectively. Median and 3-year overall-survival was 53.4 months and 75.2%, respectively. On multivariable analysis, positive surgical margin (HR 3.57, 95% CI 1.40-9.16; p = 0.008) and diameter of the BCLM (HR 1.03, 95% CI 1.01-1.06; p = 0.002) remained associated with worse OS. In selected patients, resection of breast cancer liver metastases can be done safely and a subset of patients may derive a relatively long survival, especially from a margin negative resection. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Single-Docking Full Robotic Surgery for Rectal Cancer: A Single-Center Experience.

PubMed

Alfieri, Sergio; Di Miceli, Dario; Menghi, Roberta; Cina, Caterina; Fiorillo, Claudio; Prioli, Francesca; Rosa, Fausto; Doglietto, Giovanni B; Quero, Giuseppe

2018-06-01

Robotic surgery has gradually gained importance in the treatment of rectal cancer. However, recent studies have not shown any advantages when compared with laparoscopy. The objective of this study is to report a single surgeon's experience in robotic rectal surgery focusing on short-term and long-term outcomes. Sixty consecutive robotic rectal resections for adenocarcinoma, over a 4-year period, were retrospectively reviewed. Patients' characteristics and perioperative outcomes were analyzed. Oncological outcomes and surgical resection quality as well as overall and disease-free survival were also assessed. Thirty patients out of 60 (50%) underwent neoadjuvant therapy. Anterior rectal resection was performed in 52 cases (86.7%), and abdominoperineal resection was done in 8 cases (13.3%). Mean operative time was 283 (±68.6) minutes. The conversion rate was 5% (3 patients). Postoperative complications occurred in 10 cases (16.7%), and reoperation was required in 1 case (1.7%). Mean hospital stay was 9 days, while 30-day mortality was 1.7% (1 patients). The histopathological analysis reported a negative circumferential radial margin and distal margins in 100% of cases with a complete or near complete total mesorectal excision in 98.3% of patients. Mean follow-up was 32.8 months with a recurrence rate of 3.4% (2 patients). Overall survival and disease-free survival were 94% and 87%, respectively. Robotic surgery for rectal cancer proves to be safe and feasible when performed by highly skilled surgeons. It offers acceptable perioperative outcomes with a conversion rate notably lower than with the laparoscopic approach. Adequate pathological results and long-term oncological outcomes were also obtained.

77 FR 75045 - Locomotive Safety Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-19

...), the Central Railway MFG (CRM), D. P. Honold (Honold), David Lombardi (Lombardi), Paul, Reich & Myers... more expensive and less effective. 6. Small Businesses According to the CRM's petition, the... consistent with the railroads and vendors business philosophy. Thus, FRA disagrees with the assertions of CRM...

77 FR 38581 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-28

...: Minority Business Development Agency. Title: Online Customer Relationship Management (CRM)/Performance... client information, service activities and progress on attainment of program goals via the Online CRM/Performance Databases. The data collected through the Online CRM/Performance Databases is used to regularly...

TOF-SIMS for Rapid Nuclear Forensics Evaluation of Uranium Oxide Particles

DTIC Science & Technology

2011-03-01

Fraction U-238 nU U metal CRM 112-A NBL Metal Assay and Isotopic .000052458 .0072017 --- .9927458 nUO2 UO2 --- NBL Commercial material...0 .992745 dU U metal CRM 115 NBL Uranium Assay .0000076 .0020291 .0000322 .9979311 dUO2 UO2 --- IBI Labs Commercial material --- .002- .0035...U500* U3O8 CRM U500 NBL Isotopic .005181 .49696 .000755 .49711 U900* U3O8 CRM U900 NBL Isotopic .007777 .90196 .003327 .08693 *Sample

Workshop on Integrated Crew Resource Management (CRM), 19-21 November 1991

DTIC Science & Technology

1992-03-01

VI DOT/FAAIRD-92/5 Workshop on Integrated Research and Development Service Crew Resource Washington, DC 20591 Management ( CRM ) AD-A252 980 II! Ir H... Management ( CRM ) Page i Technical Report Documentation Page 1. Report No. 2. Government Accession No. 3. Recipient’s Catalog No. DOT/FAA/RD-92/5I 4. Title and...Subtitle S. Report Date May 1992 Workshop on Integrated Crew Resource Management ( CRM ) 6. Performing Organization Code ARD-1 8. Performing

A crew resource management program tailored to trauma resuscitation improves team behavior and communication.

PubMed

Hughes, K Michael; Benenson, Ronald S; Krichten, Amy E; Clancy, Keith D; Ryan, James Patrick; Hammond, Christopher

2014-09-01

Crew Resource Management (CRM) is a team-building communication process first implemented in the aviation industry to improve safety. It has been used in health care, particularly in surgical and intensive care settings, to improve team dynamics and reduce errors. We adapted a CRM process for implementation in the trauma resuscitation area. An interdisciplinary steering committee developed our CRM process to include a didactic classroom program based on a preimplementation survey of our trauma team members. Implementation with new cultural and process expectations followed. The Human Factors Attitude Survey and Communication and Teamwork Skills assessment tool were used to design, evaluate, and validate our CRM program. The initial trauma communication survey was completed by 160 team members (49% response). Twenty-five trauma resuscitations were observed and scored using Communication and Teamwork Skills. Areas of concern were identified and 324 staff completed our 3-hour CRM course during a 3-month period. After CRM training, 132 communication surveys and 38 Communication and Teamwork Skills observations were completed. In the post-CRM survey, respondents indicated improvement in accuracy of field to medical command information (p = 0.029); accuracy of emergency department medical command information to the resuscitation area (p = 0.002); and team leader identity, communication of plan, and role assignment (p = 0.001). After CRM training, staff were more likely to speak up when patient safety was a concern (p = 0.002). Crew Resource Management in the trauma resuscitation area enhances team dynamics, communication, and, ostensibly, patient safety. Philosophy and culture of CRM should be compulsory components of trauma programs and in resuscitation of injured patients. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Pediatric crisis resource management training improves emergency medicine trainees' perceived ability to manage emergencies and ability to identify teamwork errors.

PubMed

Bank, Ilana; Snell, Linda; Bhanji, Farhan

2014-12-01

Improved pediatric crisis resource management (CRM) training is needed in emergency medicine residencies because of the variable nature of exposure to critically ill pediatric patients during training. We created a short, needs-based pediatric CRM simulation workshop with postactivity follow-up to determine retention of CRM knowledge. Our aims were to provide a realistic learning experience for residents and to help the learners recognize common errors in teamwork and improve their perceived abilities to manage ill pediatric patients. Residents participated in a 4-hour objectives-based workshop derived from a formal needs assessment. To quantify their subjective abilities to manage pediatric cases, the residents completed a postworkshop survey (with a retrospective precomponent to assess perceived change). Ability to identify CRM errors was determined via a written assessment of scripted errors in a prerecorded video observed before and 1 month after completion of the workshop. Fifteen of the 16 eligible emergency medicine residents (postgraduate year 1-5) attended the workshop and completed the surveys. There were significant differences in 15 of 16 retrospective pre to post survey items using the Wilcoxon rank sum test for non-parametric data. These included ability to be an effective team leader in general (P < 0.008), delegating tasks appropriately (P < 0.009), and ability to ensure closed-loop communication (P < 0.008). There was a significant improvement in identification of CRM errors through the use of the video assessment from 3 of the 12 CRM errors to 7 of the 12 CRM errors (P < 0.006). The pediatric CRM simulation-based workshop improved the residents' self-perceptions of their pediatric CRM abilities and improved their performance on a video assessment task.

Risk factor assessment of endoscopically removed malignant colorectal polyps

PubMed Central

Netzer, P; Forster, C; Biral, R; Ruchti, C; Neuweiler, J; Stauffer, E; Schonegg, R; Maurer, C; Husler, J; Halter, F; Schmassmann, A

1998-01-01

Background—Malignant colorectal polyps are defined as endoscopically removed polyps with cancerous tissue which has invaded the submucosa. Various histological criteria exist for managing these patients. 
Aims—To determine the significance of histological findings of patients with malignant polyps. 
Methods—Five pathologists reviewed the specimens of 85 patients initially diagnosed with malignant polyps. High risk malignant polyps were defined as having one of the following: incomplete polypectomy, a margin not clearly cancer-free, lymphatic or venous invasion, or grade III carcinoma. Adverse outcome was defined as residual cancer in a resection specimen and local or metastatic recurrence in the follow up period (mean 67months). 
Results—Malignant polyps were confirmed in 70 cases. In the 32 low risk malignant polyps, no adverse outcomes occurred; 16(42%) of the 38 patients with high risk polyps had adverse outcomes (p<0.001). Independent adverse risk factors were incomplete polypectomy and a resected margin not clearly cancer-free; all other risk factors were only associated with adverse outcome when in combination. 
Conclusion—As no patients with low risk malignant polyps had adverse outcomes, polypectomy alone seems sufficient for these cases. In the high risk group, surgery is recommended when either of the two independent risk factors, incomplete polypectomy or a resection margin not clearly cancer-free, is present or if there is a combination of other risk factors. As lymphatic or venous invasion or grade III cancer did not have an adverse outcome when the sole risk factor, operations in such cases should be individually assessed on the basis of surgical risk. 

 Keywords: malignant polyps; colon cancer; colonoscopy; polypectomy; histology PMID:9824349

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer.

PubMed

García-Cabezas, Sonia; Rodríguez-Liñán, Milagrosa; Otero-Romero, Ana M; Bueno-Serrano, Carmen M; Gómez-Barbadillo, José; Palacios-Eito, Amalia

2016-10-01

Preoperative short-course radiotherapy with immediate surgery improves local control in patients with rectal cancer. Tumor responses are smaller than those described with radiochemotherapy. Preliminary data associate this lower response to the short period until surgery. The aim of this study is to analyze the response to preoperative short-course radiotherapy and its correlation with the interval to surgery especially analyzing patients with mesorectal fascia involvement. A total of 155 patients with locally advanced rectal cancer treated with preoperative radiotherapy (5×5Gy) were retrospectively analyzed. Tumor response in terms of rates of complete pathological response, downstaging, tumor regression grading and status of the circumferential resection margin were quantified. The mean interval from radiotherapy to surgery was 23 days. The rate of complete pathological response was 2.2% and 28% experienced downstaging (stage decreased). No differences between these rates and interval to surgery were detected. Eighty-eight patients had magnetic resonance imaging for staging (in 31 patients the mesorectal fascia was involved).The mean time to surgery in patients with involvement of the fascia and R0 surgery was 27 days and 16 days if R1 (P=.016). The cutoff of 20 days reached the highest probability of achieving a free circumferential resection margin between patients with mesorectal fascia involvement, with no statistically significant differences: RR 3.036 95% CI=(0.691-13.328), P=.06. After preoperative short-course radiotherapy, an interval>20 days enhances the likelihood of achieving a free circumferential resection margin in patients with mesorectal fascia involvement. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Paired-agent imaging for resection during surgery (PAIRS) of head and neck squamous cell carcinomas (Conference Presentation)

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Tichauer, Kenneth M.; Chen, Eunice; Gunn, Jason R.; Hoopes, P. Jack; Wells, Wendy A.; Hasan, Tayyaba; Pogue, Brian W.

2016-03-01

Ninety percent of patients with head and neck squamous cell carcinomas (HNSCC) have overexpression of epidermal growth factor receptor (EGFR), which is correlated with poor prognosis. Complete surgical resection of HNSCC tumors has a large impact on patient survival, where detection of tumor at or close to surgical margins increases the risk of death at 5-years by 90%. In addition, large surgical margins can greatly increase the morbidity experienced by the patient due to functional and cosmetic damage of oral and facial structures. Single fluorescence targeting agents are often used for tumor detection in in vivo pre-clinical imaging; however, the arising signal is qualitative at best because it is a complex mixture of vascular perfusion, vascular leakage, inhibited lymphatic clearance, and receptor binding. In vivo ratiometric receptor concentration imaging (RCI) allows quantification of receptor expression (hence identification of cancerous tissue) by utilizing co-administered paired-agents consisting of a targeted agent and non-targeted perfusion agent to reference the plasma delivery and leakage. A panel of HNSCC tumors with varying levels of EGFR expression (SCC-15 >SCC-25 > SCC-09) have been imaged using ABY-029, a clinically relevant anti-EGFR affibody labeled with IRDye 800CW, and affibody control imaging agent labeled with IRDye 680RD. RCI maps of in vivo tissue have been created and are spatially correlated with EGFR and CD31 immunohistochemistry and basic H and E staining. The RCI threshold parameters for distinguishing tumor from normal tissues (skin and muscle) and the accuracy of margin detection in these tumors will be presented. RCI surgical resection will be further developed using a novel multi-channel, gated fluorescence-guided surgery (FGS) imaging system that is capable of performing RCI in normal room light.

Multiple Head and Neck Tumors Frequently Originate from a Single Preneoplastic Lesion

PubMed Central

Tabor, Maarten P.; Brakenhoff, Ruud H.; Ruijter-Schippers, Henrique J.; van der Wal, Jacqueline E.; Snow, Gordon B.; Leemans, C. René; Braakhuis, Boudewijn J. M.

2002-01-01

The development of second primary tumors has a negative impact on the prognosis of head and neck squamous cell carcinoma. Previously, we detected genetically altered and tumor-related mucosal lesions in the resection margins in 25% of unselected head and neck squamous cell carcinoma patients (Tabor MP, Brakenhoff RH, van Houten VMM, Kummer JA, Snel MHJ, Snijders PJF, Snow GB, Leemans CR, Braakhuis BJM: Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 2001, 7: 1523–1532). The aim of this study was to determine whether first and second primary tumors are clonally related and originate from a single genetically altered field. From 10 patients we analyzed the first tumor of the oral cavity or oropharynx, the >3-cm remote second primary tumor, and the mucosa from the tumor-free margins from both resection specimens. We compared TP53 mutations and loss of heterozygosity profiles using 19 microsatellite markers at chromosomes 3p, 9p, 13q, and 17p. In all patients, genetically altered mucosal lesions were detected in at least one resection margin from both first and second primary tumor. Evidence for a common clonal origin of the first tumor, second primary tumor, and the intervening mucosa was found for at least 6 of 10 patients. Our results indicate that a proportion of multiple primary tumors have developed within a single preneoplastic field. Based on different etiology and clinical consequences, we propose that independent second primary tumors should be distinguished from second field tumors, that arise from the same genetically altered field the first tumor has developed from. PMID:12213734

Imaging Analysis of Hepatoblastoma Resectability Across Neoadjuvant Chemotherapy

PubMed Central

Murphy, Andrew J.; Ayers, Gregory D.; Hilmes, Melissa A.; Mukherjee, Kaushik; Wilson, Kevin J.; Allen, Wade M.; Fernandez-Pineda, Israel; Shinall, Myrick C.; Zhao, Zhiguo; Furman, Wayne L.; McCarville, Mary Beth; Davidoff, Andrew M.; Lovvorn, Harold N.

2013-01-01

Purpose Hepatoblastomas often require neoadjuvant chemotherapy to facilitate partial hepatectomy, which necessitates freedom of tumor borders from the confluence of hepatic veins (COHV), portal vein bifurcation (PVB), and retrohepatic inferior vena cava (IVC). This study aimed to clarify the effect of incremental neoadjuvant cycles on the AHEP0731 protocol criteria of hepatoblastoma resectability. Methods Hepatoblastoma responses to neoadjuvant chemotherapy were analyzed among patients (n=23) treated at two children’s hospitals between 1996 and 2010. Using digital imaging data, ellipsoid and point-based models were created to measure tumor volume regression and respective distances from tumor borders nearest to the COHV, PVB, and IVC. Results Hepatoblastoma volumes regressed with incremental neoadjuvant chemotherapy cycles (p<0.001). Although tumor borders regressed away from the COHV (p=0.008), on average only 1.1mm was gained. No change from tumor borders to the PVB was detected (p=0.102). Distances from tumor borders to the IVC remained stable at one hospital (p=0.612), but increased only 0.15mm every 10 days of therapy at the other (p=0.002). Neoadjuvant chemotherapy induced slightly more tumors to meet the threshold vascular margin of 1cm (baseline to completion): COHV, 11 (47.8%) to 17 (73.9%; p=0.058); PVB, 11 (47.8%) to 15 (65.2%; p=0.157); IVC, 4 (17.4%) to 10 (43.5%; p=0.034). No differences were detected in demographic or disease-specific characteristics between patients who did or did not achieve this 1cm margin after conclusion of chemotherapy. Conclusion Hepatoblastoma volumes regress significantly with increasing neoadjuvant chemotherapy cycles. However, tumors often remain anchored to the major hepatic vasculature, showing marginal improvement in resectability criteria. PMID:23845613

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

Fury, Matthew G.; Department of Medicine, Weill Cornell Medical College, New York, New York; Lee, Nancy Y.

Purpose: Elevated expression of eukaryotic protein synthesis initiation factor 4E (eIF4E) in histologically cancer-free margins of resected head and neck squamous cell carcinomas (HNSCCs) is mediated by mammalian target of rapamycin complex 1 (mTORC1) and has been associated with increased risk of disease recurrence. Preclinically, inhibition of mTORC1 with everolimus sensitizes cancer cells to cisplatin and radiation. Methods and Materials: This was single-institution phase 1 study to establish the maximum tolerated dose of daily everolimus given with fixed dose cisplatin (30 mg/m{sup 2} weekly × 6) and concurrent intensity modulated radiation therapy for patients with locally and/or regionally advanced head-and-neckmore » cancer. The study had a standard 3 + 3 dose-escalation design. Results: Tumor primary sites were oral cavity (4), salivary gland (4), oropharynx (2), nasopharynx (1), scalp (1), and neck node with occult primary (1). In 4 of 4 cases in which resected HNSCC surgical pathology specimens were available for immunohistochemistry, elevated expression of eIF4E was observed in the cancer-free margins. The most common grade ≥3 treatment-related adverse event was lymphopenia (92%), and dose-limiting toxicities (DLTs) were mucositis (n=2) and failure to thrive (n=1). With a median follow up of 19.4 months, 2 patients have experienced recurrent disease. The maximum tolerated dose was everolimus 5 mg/day. Conclusions: Head-and-neck cancer patients tolerated everolimus at therapeutic doses (5 mg/day) given with weekly cisplatin and intensity modulated radiation therapy. The regimen merits further evaluation, especially among patients who are status post resection of HNSCCs that harbor mTORC1-mediated activation of eIF4E in histologically negative surgical margins.« less

Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals.

PubMed

Fung, Ho Yee Joyce; Fu, Szu-Chin; Chook, Yuh Min

2017-03-10

Nuclear export receptor CRM1 binds highly variable nuclear export signals (NESs) in hundreds of different cargoes. Previously we have shown that CRM1 binds NESs in both polypeptide orientations (Fung et al., 2015). Here, we show crystal structures of CRM1 bound to eight additional NESs which reveal diverse conformations that range from loop-like to all-helix, which occupy different extents of the invariant NES-binding groove. Analysis of all NES structures show 5-6 distinct backbone conformations where the only conserved secondary structural element is one turn of helix that binds the central portion of the CRM1 groove. All NESs also participate in main chain hydrogen bonding with human CRM1 Lys568 side chain, which acts as a specificity filter that prevents binding of non-NES peptides. The large conformational range of NES backbones explains the lack of a fixed pattern for its 3-5 hydrophobic anchor residues, which in turn explains the large array of peptide sequences that can function as NESs.

Immunogenicity and safety of a quadrivalent meningococcal polysaccharide CRM conjugate vaccine in infants and toddlers.

PubMed

Tregnaghi, Miguel; Lopez, Pio; Stamboulian, Daniel; Graña, Gabriela; Odrljin, Tatjana; Bedell, Lisa; Dull, Peter M

2014-09-01

This phase III study assessed the safety and immunogenicity of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, administered with routine vaccines starting at 2 months of age. Healthy infants received MenACWY-CRM in a two- or three-dose primary infant series plus a single toddler dose. In addition, a two-dose toddler catch-up series was evaluated. Immune responses to MenACWY-CRM were assessed for serum bactericidal activity with human complement (hSBA). Reactogenicity and safety results were collected systematically. After a full infant/toddler series or two-dose toddler catch-up series, MenACWY-CRM elicited immune responses against the four serogroups in 94-100% of subjects. Noninferiority of the two- versus three-dose MenACWY-CRM infant dosing regimen was established for geometric mean titers for all serogroups. Following the three-dose infant primary series, 89-98% of subjects achieved an hSBA ≥ 8 across all serogroups. Immune responses to concomitant routine vaccines given with MenACWY-CRM were noninferior to responses to routine vaccines alone, except for pertactin after the two-dose infant series. Noninferiority criteria were met for all concomitant antigens after the three-dose infant series. MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Improving staff perception of a safety climate with crew resource management training.

PubMed

Kuy, SreyRam; Romero, Ramon A L

2017-06-01

Communication failure is one of the top root causes in patient safety adverse events. Crew resource management (CRM) is a team building communication process intended to improve patient safety by improving team dynamics. First, to describe implementation of CRM in a Veterans Affair (VA) surgical service. Second, to assess whether staff CRM training is related to improvement in staff perception of a safety climate. Mandatory CRM training was implemented for all surgical service staff at a VA Hospital at 0 and 12 mo. Safety climate questionnaires were completed by operating room staff at a baseline, 6 and 12 mo after the initial CRM training. Participants reported improvement on all 27 points on the safety climate questionnaire at 6 mo compared with the baseline. At 12 mo, there was sustained improvement in 23 of the 27 areas. This is the first published report about the effect of CRM training on staff perception of a safety climate in a VA surgical service. We demonstrate that CRM training can be successfully implemented widespread in a surgical program. Overall, there was improvement in 100% of areas assessed on the safety climate questionnaire at 6 mo after CRM training. By 1 y, this improvement was sustained in 23 of 27 areas, with the areas of greatest improvement being the performance of briefings, collaboration between nurses and doctors, valuing nursing input, knowledge about patient safety, and institutional promotion of a patient safety climate. Published by Elsevier Inc.

Targeted delivery of rosmarinic acid across the blood-brain barrier for neuronal rescue using polyacrylamide-chitosan-poly(lactide-co-glycolide) nanoparticles with surface cross-reacting material 197 and apolipoprotein E.

PubMed

Kuo, Yung-Chih; Rajesh, Rajendiran

2017-08-07

Rosmarinic acid-loaded polyacrylamide-chitosan-poly(lactide-co-glycolide) nanoparticles (RA-PAAM-CH-PLGA NPs) were grafted with cross-reacting material 197 (CRM197) and apolipoprotein E (ApoE) for targeting of the blood-brain barrier (BBB) and rescuing degenerated neurons. The polymeric nanocarriers were prepared by microemulsion, solvent diffusion, grafting, and surface modification, and CRM197-ApoE-RA-PAAM-CH-PLGA NPs were used to treat human brain-microvascular endothelial cells, RWA264.7 cells, and Aβ-insulted SK-N-MC cells. Experimental results revealed that an increase in the weight percentage of PAAM decreased the particle size, zeta potential, and grafting efficiency of CRM197 and ApoE. In addition, surface DSPE-PEG(2000) could protect CRM197-ApoE-RA-PAAM-CH-PLGA NPs against uptake by RWA264.7 cells. An increase in the concentration of CRM197 and ApoE decreased the transendothelial electrical resistance and increased the ability of propidium iodide and RA to cross the BBB. The order in the viability of apoptotic SK-N-MC cells was CRM197-ApoE-RA-PAAM-CH-PLGA NPs > CRM197-RA-PAAM-CH-PLGA NPs > RA. Thus, CRM197-ApoE-RA-PAAM-CH-PLGA NPs can be a promising formulation to deliver RA to Aβ-insulted neurons in the pharmacotherapy of Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Pneumococcal Conjugate Vaccines and Otitis Media: An Appraisal of the Clinical Trials

PubMed Central

Fletcher, Mark A.; Fritzell, Bernard

2012-01-01

Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POET; vaccine, 11-valent PCV [PCV11]-PD). For the microbiological endpoint, vaccine efficacy against vaccine-serotype pneumococcal otitis media was about 60% across trials. Against the clinical endpoint of all episodes, vaccine efficacy was 7% (PCV7-CRM/NCKP), 6% (PCV7-CRM/FinOM), −1% (PCV7-OMPC/FinOM), and −0.4% (PCV7-CRM/Native American Trial); 34% against first episodes of ear, nose, and throat specialist-referral cases (PCV11-PD/POET). Both follow-up through 2 years of age, for the 5 trials, and long-term follow-up, for PCV7-CRM/NCKP and PCV7-CRM/FinOM, demonstrated greater vaccine efficacy against recurrent AOM and tympanostomy-tube placement, suggesting that vaccination against early episodes of AOM may prevent subsequent episodes of complicated otitis media. Although study designs varied by primary endpoint measured, age at follow-up, source of middle-ear fluid for culture, case ascertainment, and type of randomization, each clinical trial demonstrated vaccine efficacy against microbiological and/or clinical otitis media. PMID:22701486

Robotic versus laparoscopic proctectomy for rectal cancer: a meta-analysis.

PubMed

Memon, Sameer; Heriot, Alexander G; Murphy, Declan G; Bressel, Mathias; Lynch, A Craig

2012-07-01

Robot-assisted laparoscopic surgery is being performed more frequently for the minimally invasive management of rectal cancer. The objective of this meta-analysis was to compare the clinical and oncologic safety and efficacy of robot-assisted versus conventional laparoscopic surgery. A search of the Medline and Embase databases was performed for studies that compared clinical or oncologic outcomes of conventional laparoscopic proctectomy with robot-assisted laparoscopic proctectomy for rectal cancer. The methodological quality of the selected studies was critically assessed to identify studies suitable for inclusion. Meta-analysis was performed by a random effects model and analyzed by Review Manager. Clinical outcomes evaluated were conversion rates, operation times, length of hospital stay, and complications. Oncologic outcomes evaluated were circumferential margin status, number of lymph nodes collected, and distal resection margin lengths. Eight comparative studies were assessed for quality, and seven studies were included in the meta-analysis. Two studies were matched case-control studies, and five were unmatched. A total of 353 robot-assisted laparoscopic surgery proctectomy cases and 401 conventional laparoscopic surgery proctectomy cases were analyzed. Robotic surgery was associated with a significantly lower conversion rate (P=0.03; 95% confidence interval 1-12). There was no difference in complications, circumferential margin involvement, distal resection margin, lymph node yield, or hospital stay (P=NS). Robot-assisted surgery decreased the conversion rate compared to conventional laparoscopic surgery. Other clinical outcomes and oncologic outcomes were equivalent. The benefits of robotic rectal cancer surgery may differ between population groups.

Intraoperative imaging using intravascular contrast agent

NASA Astrophysics Data System (ADS)

Watson, Jeffrey R.; Martirosyan, Nikolay; Garland, Summer; Lemole, G. Michael; Romanowski, Marek

2016-03-01

Near-infrared (NIR) contrast agents are becoming more frequently studied in medical imaging due to their advantageous characteristics, most notably the ability to capture near-infrared signal across the tissue and the safety of the technique. This produces a need for imaging technology that can be specific for both the NIR dye and medical application. Indocyanine green (ICG) is currently the primary NIR dye used in neurosurgery. Here we report on using the augmented microscope we described previously for image guidance in a rat glioma resection. Luc-C6 cells were implanted in a rat in the left-frontal lobe and grown for 22 days. Surgical resection was performed by a neurosurgeon using augmented microscopy guidance with ICG contrast. Videos and images were acquired to evaluate image quality and resection margins. ICG accumulated in the tumor tissue due to enhanced permeation and retention from the compromised bloodbrain- barrier. The augmented microscope was capable of guiding the rat glioma resection and intraoperatively highlighted tumor tissue regions via ICG fluorescence under normal illumination of the surgical field.

[Histological classification: evaluation of resection specimens of EMR/ESD--response evaluation after neoadjuvant therapy].

PubMed

Munding, J; Ziebarth, W; Belyaev, O; Uhl, W; Tannapfel, A

2013-12-01

The surveillance of patients with Barrett mucosa in the distal oesophagus leads to an increase of patients diagnosed with early cancer of the oesophagogastric junction and stomach with only superficial infiltration. Comparable to Asian countries where screening of patients at risk is recommended due to the high incidence of gastric cancer, endoscopic resection of early cancer in the stomach and distal oesophagus is increasing. In spite of the special endoscopic techniques--there are several requirements for the resected specimen which ensure its exact pathohistological evaluation. This is necessary to detect the exact depth of infiltration and the resection margins. To provide an exact pathohistological diagnosis is important for further therapeutic implications and prognosis. Advanced carcinomas of the oesophagus and stomach need multimodal treatment with radiation and chemotherapy. This has a special impact on the tumour which leads to pathohistological detectable changes as estimated in the so-called regression grading. Georg Thieme Verlag KG Stuttgart · New York.

Type of Resection (Whipple vs. Distal) Does Not Affect the National Failure to Provide Post-resection Adjuvant Chemotherapy in Localized Pancreatic Cancer.

PubMed

Bergquist, John R; Ivanics, Tommy; Shubert, Christopher R; Habermann, Elizabeth B; Smoot, Rory L; Kendrick, Michael L; Nagorney, David M; Farnell, Michael B; Truty, Mark J

2017-06-01

Adjuvant chemotherapy improves survival after curative intent resection for localized pancreatic adenocarcinoma (PDAC). Given the differences in perioperative morbidity, we hypothesized that patients undergoing distal partial pancreatectomy (DPP) would receive adjuvant therapy more often those undergoing pancreatoduodenectomy (PD). The National Cancer Data Base (2004-2012) identified patients with localized PDAC undergoing DPP and PD, excluding neoadjuvant cases, and factors associated with receipt of adjuvant therapy were identified. Overall survival (OS) was analyzed using multivariable Cox proportional hazards regression. Overall, 13,501 patients were included (DPP, n = 1933; PD, n = 11,568). Prognostic characteristics were similar, except DPP patients had fewer N1 lesions, less often positive margins, more minimally invasive resections, and shorter hospital stay. The proportion of patients not receiving adjuvant chemotherapy was equivalent (DPP 33.7%, PD 32.0%; p = 0.148). The type of procedure was not independently associated with adjuvant chemotherapy (hazard ratio 0.96, 95% confidence interval 0.90-1.02; p = 0.150), and patients receiving adjuvant chemotherapy had improved unadjusted and adjusted OS compared with surgery alone. The type of resection did not predict adjusted mortality (p = 0.870). Receipt of adjuvant chemotherapy did not vary by type of resection but improved survival independent of procedure performed. Factors other than type of resection appear to be driving the nationwide rates of post-resection adjuvant chemotherapy in localized PDAC.

Outcomes of levator resection at tertiary eye care center in Iran: a 10-year experience.

PubMed

Abrishami, Alireza; Bagheri, Abbas; Salour, Hossein; Aletaha, Maryam; Yazdani, Shahin

2012-02-01

To assess outcomes of levator resection for the surgical correction of congenital and acquired upper lid ptosis in patients with fair to good levator function and evaluation of the relationship between demographic data and success of this operation. In a retrospective study, medical records of patients with blepharoptosis who had undergone levator resection over a 10-year period and were followed for at least 3 months were reviewed. Overall, 136 patients including 60 (44.1%) male and 76 (55.9%) female subjects with a mean age of 20 ± 13.8 years (range, 2 to 80 years) were evaluated, of whom 120 cases (88.2%) had congenital ptosis and the rest had acquired ptosis. The overall success rate after the first operation was 78.7%. The most common complication after the first operation was undercorrection in 26 cases (19.1%), which was more prevalent among young patients (p = 0.06). Lid fissure and margin reflex distance (MRD(1)) also increased after levator resection (p < 0.001). Age, sex, type of ptosis, amblyopia, levator function, MRD(1), lid fissure and spherical equivalent were not predictive of surgical outcomes of levator resection. Levator resection has a high rate of success and few complications in the surgical treatment of congenital and acquired upper lid ptosis with fair to good levator function. Reoperation can be effective in most cases in which levator resection has been performed.

Pancreatoduodenectomy with portal vein resection for distal cholangiocarcinoma.

PubMed

Maeta, T; Ebata, T; Hayashi, E; Kawahara, T; Mizuno, S; Matsumoto, N; Ohta, S; Nagino, M

2017-10-01

Little is known about the value of portal vein (PV) resection in distal cholangiocarcinoma. The aim of this study was to evaluate the clinical significance of PV resection in distal cholangiocarcinoma. Patients who underwent pancreatoduodenectomy (PD) for distal cholangiocarcinoma between 2001 and 2010 at one of 31 hospitals in Japan were reviewed retrospectively with special attention to PV resection. Short- and long-term outcomes were evaluated. In the study interval, 453 consecutive patients with distal cholangiocarcinoma underwent PD, of whom 31 (6·8 per cent) had combined PV resection. The duration of surgery (510 versus 427 min; P = 0·005) and incidence of blood transfusion (48 versus 30·7 per cent; P = 0·042) were greater in patients who had PV resection than in those who did not. Postoperative morbidity and mortality were no different in the two groups. Several indices of tumour progression, including high T classification, lymphatic invasion, perineural invasion, pancreatic invasion and lymph node metastasis, were more common in patients who had PV resection. Consequently, the incidence of R1/2 resection was higher in this group (32 versus 11·8 per cent; P = 0·004). Survival among the 31 patients with PV resection was worse than that for the 422 patients without PV resection (15 versus 42·4 per cent at 5 years; P < 0·001). Multivariable analyses revealed that age, blood loss, histological grade, perineural invasion, pancreatic invasion, lymph node metastasis and surgical margin were independent risk factors for overall survival. PV resection was not an independent risk factor. PV invasion in distal cholangiocarcinoma is associated with locally advanced disease and several negative prognostic factors. Survival for patients who have PV resection is poor even after curative resection. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

Early and Long-Term Outcomes of Patients Undergoing Liver Resection and Diaphragm Excision for Advanced Colorectal Liver Metastases

PubMed Central

Lordan, Jeffrey T; Riga, Angela; Worthington, Tim R; Karanjia, Nariman D

2009-01-01

INTRODUCTION At present, liver resection offers the best long-term outcome and only chance for cure in patients with colorectal liver metastases. However, there are no large series that report the early and long-term outcomes of patients who require simultaneous diaphragm excision. This study was designed to investigate these patients. PATIENTS AND METHODS A total of 285 consecutive liver resections were performed over a 10-year period. Of these, 258 had liver resections alone and 27 underwent liver resection and simultaneous diaphragm excision. Data were collected prospectively and analysed retrospectively. Pre-operative assessment was standardised. The outcomes between the two groups were compared. RESULT There was no difference in age, hospital stay or intra-operative blood loss. The diaphragm was histologically involved in four out of 27 resections. As a result, the cancer involved resection margin incidence was greater in the liver resection and diaphragm excision group (14.8% versus 3.9%; P = 0.12). The median tumour size was also different between the two groups (60 mm versus 30 mm; P = 0.001). The liver and diaphragm resection group had a greater peri-operative complication rate (44.4% versus 21.3%; P = 0.02) and mortality (7.4% versus 1.6%; P = 0.25). Overall and disease-free survival was significantly worse in the group who underwent simultaneous diaphragm excision and liver resection (P = 0.04 and P = 0.005, respectively). Diaphragm invasion was found to be an independent predictor of poor overall outcome (P = 0.02). CONCLUSION Liver resection and simultaneous diaphragm excision have a greater incidence of peri-operative morbidity and mortality and a significantly worse long-term outcome compared with liver resection alone. However, these data suggest that liver resection in the presence of diaphragm invasion may still offer a favourable outcome compared with chemotherapy treatment alone. Therefore, we believe that diaphragm involvement by tumour should not be a contra-indication to hepatectomy. PMID:19558763

Implications of the Index Cholecystectomy and Timing of Referral for Radical Resection of Advanced Incidental Gallbladder Cancer

PubMed Central

Ausania, F; White, SA; French, JJ; Jaques, BC; Charnley, RM; Manas, DM

2015-01-01

Introduction Advanced (pT2/T3) incidental gallbladder cancer is often deemed unresectable after restaging. This study assesses the impact of the primary operation, tumour characteristics and timing of management on re-resection. Methods The records of 60 consecutive referrals for incidental gallbladder cancer in a single tertiary centre from 2003 to 2011 were reviewed retrospectively. Decision on re-resection of incidental gallbladder cancer was based on delayed interval restaging at three months following cholecystectomy. Demographics, index cholecystectomy data, primary pathology, CA19–9 tumour marker levels at referral and time from cholecystectomy to referral as well as from referral to restaging were analysed. Results Thirty-seven patients with pT2 and twelve patients with pT3 incidental gallbladder cancer were candidates for radical re-resection. Following interval restaging, 24 patients (49%) underwent radical resection and 25 (51%) were deemed inoperable. The inoperable group had significantly more patients with positive resection margins at cholecystectomy (p=0.002), significantly higher median CA19–9 levels at referral (p=0.018) and were referred significantly earlier (p=0.004) than the patients who had resectable tumours. On multivariate analysis, urgent referral (p=0.036) and incomplete cholecystectomy (p=0.048) were associated significantly with inoperable disease following restaging. Conclusions In patients with incidental, potentially resectable, pT2/T3 gallbladder cancer, inappropriate index cholecystectomy may have a significant impact on tumour dissemination. Early referral of breached tumours is not associated with resectability. PMID:25723690

78 FR 78359 - Agency Information Collection Activities; Proposed Collection; Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

...: Regional Extension Center Cooperative Agreement Program (CRM Tool). OMB No.: 0955-0009 Abstract: The Customer Relationship Management (CRM) application is a nimble business intelligence tool being used by more than 1,500 users at ONC partner organizations and grantees. The CRM collects data from a large...

Molecular analysis of citrus rust (Phyllocoptruta oleivora) populations in Texas

USDA-ARS?s Scientific Manuscript database

Phyllocoptruta olevoria (Acari: Eriophyidae) or the citrus rust mite (CRM) is one of the most economically important mite pests of citrus worldwide. CRM originated from Asia, however it is found in most citrus producing areas, such as, Brazil, Morocco and the United States. Though CRM is a major pes...

78 FR 69097 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

... (CRM) system to improve the response to correspondences from individuals seeking information from a... and private sector sources.'' The SalesForce CRM provides a centralized portal to manage frequently... topics. Depending on the topic searched, the CRM queries the database of pre-approved questions and...

Removing the Taboo on the Surgical Violation (Cut-Through) of Cancer.

PubMed

Robbins, K Thomas; Bradford, Carol R; Rodrigo, Juan P; Suárez, Carlos; de Bree, Remco; Kowalski, Luiz P; Rinaldo, Alessandra; Silver, Carl E; Lund, Valerie J; Nibu, Ken-Ichi; Ferlito, Alfio

2016-10-01

The surgical dictum of en bloc resection without violating cancer tissue has been challenged by novel treatments in head and neck cancer. An analysis of treatment outcomes involving piecemeal removal of sinonasal, laryngeal, oropharyngeal, and hypopharyngeal cancer shows that it did not compromise tumor control. The rationale for the evolution toward use of this technique is outlined. While complete resection with clear margins remains a key end point in surgical oncology, we believe it is time to acknowledge that this time-honored dictum of avoiding tumor violation is no longer valid in selected situations.

Paratesticular aggressive angiomyxoma: A rare case

PubMed Central

Ismail, Muhamad Izwan; Wong, Yin Ping; Tan, Guan Hee; Fam, Xeng Inn

2017-01-01

Aggressive angiomyxoma (AAM) particularly testicular origin is a rare benign mesenchymal myxoid tumor which is locally aggressive, blatant for local recurrence, and may metastasize. It occurs mostly in females of childbearing age and extremely rare in males. AMM particular testicular origin is not reported in literature yet. This is a 65-year-old man who had a right scrotal swelling. Ultrasound scrotum showed a soft tissue tumor of the right testis. The patient underwent radical right orchidectomy of which histopathologically confirmed to be a paratesticular AAM with clear resection margins. There were no signs of local recurrence or metastasis 2 years postsurgical resection. PMID:28479778

Paratesticular aggressive angiomyxoma: A rare case.

PubMed

Ismail, Muhamad Izwan; Wong, Yin Ping; Tan, Guan Hee; Fam, Xeng Inn

2017-01-01

Aggressive angiomyxoma (AAM) particularly testicular origin is a rare benign mesenchymal myxoid tumor which is locally aggressive, blatant for local recurrence, and may metastasize. It occurs mostly in females of childbearing age and extremely rare in males. AMM particular testicular origin is not reported in literature yet. This is a 65-year-old man who had a right scrotal swelling. Ultrasound scrotum showed a soft tissue tumor of the right testis. The patient underwent radical right orchidectomy of which histopathologically confirmed to be a paratesticular AAM with clear resection margins. There were no signs of local recurrence or metastasis 2 years postsurgical resection.

Marshall properties of asphalt concrete using crumb rubber modified of motorcycle tire waste

NASA Astrophysics Data System (ADS)

Siswanto, Henri; Supriyanto, Bambang; Pranoto, Chandra, Pria Rizky; Hakim, Arief Rahman

2017-09-01

The aim of this study is to explain the effect of Crumb Rubber Modified (CRM) of motorcycle tire waste on Marshall properties of asphalt mix. Two types of aggregate gradation, asphalt concrete wearing course (ACWC) and asphalt concrete base (ACB), and CRM passing #50 sieve size were used. Seven levels of CRM content were investigated in this study, namely 0%, 0.5%, 1%, 1.5%, 3%, 4.5%, and 6% by weight of aggregate. Marshall test is conducted on Marshall specimens. The specimens are tested in their optimum binder content (OBC). The results indicate that CRM addition of motorcycle tire waste increases the Marshall stability of the both mix, ACWC and ACB. In addition, 1% CRM addition of motorcycle tire waste of the total mix weight is the best mix.

A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation

PubMed Central

Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A.; Gong, Yongquan; Fischbein, Michael P.; Robbins, Robert C.; Naesens, Maarten

2013-01-01

Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design. PMID:24127489

A CRM domain protein functions dually in group I and group II intron splicing in land plant chloroplasts.

PubMed

Asakura, Yukari; Barkan, Alice

2007-12-01

The CRM domain is a recently recognized RNA binding domain found in three group II intron splicing factors in chloroplasts, in a bacterial protein that associates with ribosome precursors, and in a family of uncharacterized proteins in plants. To elucidate the functional repertoire of proteins with CRM domains, we studied CFM2 (for CRM Family Member 2), which harbors four CRM domains. RNA coimmunoprecipitation assays showed that CFM2 in maize (Zea mays) chloroplasts is associated with the group I intron in pre-trnL-UAA and group II introns in the ndhA and ycf3 pre-mRNAs. T-DNA insertions in the Arabidopsis thaliana ortholog condition a defective-seed phenotype (strong allele) or chlorophyll-deficient seedlings with impaired splicing of the trnL group I intron and the ndhA, ycf3-int1, and clpP-int2 group II introns (weak alleles). CFM2 and two previously described CRM proteins are bound simultaneously to the ndhA and ycf3-int1 introns and act in a nonredundant fashion to promote their splicing. With these findings, CRM domain proteins are implicated in the activities of three classes of catalytic RNA: group I introns, group II introns, and 23S rRNA.

A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.

PubMed

Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

2013-10-21

Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.

A certified urea reference material (NMIJ CRM 6006-a) as a reliable calibrant for the elemental analyses of amino acids and food samples.

PubMed

Itoh, Nobuyasu; Yamazaki, Taichi; Sato, Ayako; Numata, Masahiko; Takatsu, Akiko

2014-01-01

We examined the reliability of a certified reference material (CRM) for urea (NMIJ CRM 6006-a) as a calibrant for N, C, and H in elemental analyzers. Only the N content for this CRM is provided as an indicative value. To estimate the C and H contents of the urea CRM, we took into account the purity of the urea and the presence of other identified impurities. When we examined the use of various masses of the calibrant (0.2 to 2 mg), we unexpectedly observed low signal intensities for small masses of H and N, but these plateaued at about 2 mg. We therefore analyzed four amino acid CRMs and four food CRMs on a 2-mg scale with the urea CRM as the calibrant. For the amino acid CRMs, the differences in the analytical and theoretical contents (≤0.0026 kg/kg) were acceptable with good repeatability (≤0.0013 kg/kg in standard deviation; n = 4). For food CRMs, comparable repeatabilities to those obtained with amino acid CRMs (≤0.0025 kg/kg in standard deviation; n = 4) were obtained. The urea CRM can therefore be used as a reliable calibrant for C, H, and N in an elemental analyzer.

TNF binding protein of variola virus acts as a TNF antagonist at epicutaneous application.

PubMed

Gileva, Irina P; Viazovaia, Elena A; Toporkova, Ludmila B; Tsyrendorzhiev, Dondok D; Shchelkunov, Sergei N; Orlovskaya, Irina A

2015-01-01

VARV-CrmB is a TNF binding protein of variola virus. VARV-CrmB protein was previously shown to be active as a TNF-antagonist in a number of in vivo and in vitro models. Here we investigated the epicutaneous effect of recombinant VARV-CrmB protein using an experimental model of muTNFinduced migration of skin leukocytes as well as colony forming activity of bone marrow cells (BMC). Epiсutaneous applications of muTNF enhanced the number of cells migrating from skin flaps of BALB/c mice, whereas subsequent applications of VARV-CrmB protein in 30 min after muTNF, abolished that effect. Epicutaneously applied muTNF influenced the activity of committed hematopoietic progenitors causing a reduction of erythroid (BFUe+CFUe) colonies and increase of granulocyte-macrophage (CFU-GM) colonies in the colony-forming tests. VARV-CrmB, applied in combination with muTNF, demonstrated an ability to reverse this effect, namely, to increase BFUe+CFUe and reduce CFU-GM back to the control levels. Taking together, these data demonstrate the TNF-blocking properties of VARV-CrmB in vivo at epicutaneous applications. As effective TNF antagonist VARV-CrmB protein might be conceded as a beneficial candidate for future research and development of therapeutic approaches in the field of inflammatory skin diseases.

Development and co-validation of porcine insulin certified reference material by high-performance liquid chromatography-isotope dilution mass spectrometry.

PubMed

Wu, Liqing; Takatsu, Akiko; Park, Sang-Ryoul; Yang, Bin; Yang, Huaxin; Kinumi, Tomoya; Wang, Jing; Bi, Jiaming; Wang, Yang

2015-04-01

This article concerns the development and co-validation of a porcine insulin (pINS) certified reference material (CRM) produced by the National Institute of Metrology, People's Republic of China. Each CRM unit contained about 15 mg of purified solid pINS. The moisture content, amount of ignition residue, molecular mass, and purity of the pINS were measured. Both high-performance liquid chromatography-isotope dilution mass spectrometry and a purity deduction method were used to determine the mass fraction of the pINS. Fifteen units were selected to study the between-bottle homogeneity, and no inhomogeneity was observed. A stability study concluded that the CRM was stable for at least 12 months at -20 °C. The certified value of the CRM was (0.892 ± 0.036) g/g. A co-validation of the CRM was performed among Chinese, Japanese, and Korean laboratories under the framework of the Asian Collaboration on Reference Materials. The co-validation results agreed well with the certified value of the CRM. Consequently, the pINS CRM may be used as a calibration material or as a validation standard for pharmaceutical purposes to improve the quality of pharmaceutical products.

Effect of CRM team leader training on team performance and leadership behavior in simulated cardiac arrest scenarios: a prospective, randomized, controlled study.

PubMed

Fernandez Castelao, Ezequiel; Boos, Margarete; Ringer, Christiane; Eich, Christoph; Russo, Sebastian G

2015-07-24

Effective team leadership in cardiopulmonary resuscitation (CPR) is well recognized as a crucial factor influencing performance. Generally, leadership training focuses on task requirements for leading as well as non-leading team members. We provided crisis resource management (CRM) training only for designated team leaders of advanced life support (ALS) trained teams. This study assessed the impact of the CRM team leader training on CPR performance and team leader verbalization. Forty-five teams of four members each were randomly assigned to one of two study groups: CRM team leader training (CRM-TL) and additional ALS-training (ALS add-on). After an initial lecture and three ALS skill training tutorials (basic life support, airway management and rhythm recognition/defibrillation) of 90-min each, one member of each team was randomly assigned to act as the team leader in the upcoming CPR simulation. Team leaders of the CRM-TL groups attended a 90-min CRM-TL training. All other participants received an additional 90-min ALS skill training. A simulated CPR scenario was videotaped and analyzed regarding no-flow time (NFT) percentage, adherence to the European Resuscitation Council 2010 ALS algorithm (ADH), and type and rate of team leader verbalizations (TLV). CRM-TL teams showed shorter, albeit statistically insignificant, NFT rates compared to ALS-Add teams (mean difference 1.34 (95% CI -2.5, 5.2), p = 0.48). ADH scores in the CRM-TL group were significantly higher (difference -6.4 (95% CI -10.3, -2.4), p = 0.002). Significantly higher TLV proportions were found for the CRM-TL group: direct orders (difference -1.82 (95% CI -2.4, -1.2), p < 0.001); undirected orders (difference -1.82 (95% CI -2.8, -0.9), p < 0.001); planning (difference -0.27 (95% CI -0.5, -0.05) p = 0.018) and task assignments (difference -0.09 (95% CI -0.2, -0.01), p = 0.023). Training only the designated team leaders in CRM improves performance of the entire team, in particular guideline adherence and team leader behavior. Emphasis on training of team leader behavior appears to be beneficial in resuscitation and emergency medical course performance.

Prospective multicenter registration study of colorectal cancer: significant variations in radicality and oncosurgical quality-Swiss Group for Clinical Cancer Research Protocol SAKK 40/00.

PubMed

Maurer, Christoph A; Dietrich, Daniel; Schilling, Martin K; Metzger, Urs; Laffer, Urban; Buchmann, Peter; Lerf, Bruno; Villiger, Peter; Melcher, Gian; Klaiber, Christian; Bilat, Christian; Brauchli, Peter; Terracciano, Luigi; Kessler, Katharina

2017-01-01

This study aimed to investigate in a multicenter cohort study the radicality of colorectal cancer resections, to assess the oncosurgical quality of colorectal specimens, and to compare the performance between centers. One German and nine Swiss hospitals agreed to prospectively register all patients with primary colorectal cancer resected between September 2001 and June 2005. The median number of eligible patients with one primary tumor included per center was 95 (range 12-204). The following variations of median values or percentages between centers were found: length of bowel specimen 20-39 cm (25.8 cm), maximum height of mesocolon 6.5-12.5 cm (9.0 cm), number of examined lymph nodes 9-24 (16), distance to nearer bowel resection margin in colon cancer 4.8-12 cm (7 cm), and in rectal cancer 2-3 cm (2.5 cm), central ligation of major artery 40-97 % (71 %), blood loss 200-500 ml (300 ml), need for perioperative blood transfusion 5-40 % (19 %), tumor opened during mobilization 0-11 % (5 %), T4-tumors not en-bloc resected 0-33 % (4 %), inadvertent perforation of mesocolon/mesorectum 0-8 % (4 %), no-touch isolation technique 36-86 % (67 %), abdominoperineal resection for rectal cancer 0-30 % (17 %), rectal cancer specimen with circumferential margin ≤1 mm 0-19 % (10 %), in-hospital mortality 0-6 % (2 %), anastomotic leak or intra-abdominal abscess 0-17 % (7 %), re-operation 0-17 % (8 %). In colorectal cancer, surgery considerable variations between different centers were found with regard to radicality and oncosurgical quality, suggesting a potential for targeted improvement of surgical technique.

Half forehead reconstruction with a single rotational scalp flap for dermatofibrosarcoma protuberans treatment

PubMed Central

2012-01-01

Background Dermatofibrosarcoma protuberans (DFSP) is a soft tissue neoplasm of intermediate to low-grade malignancy. Although metastasis rarely occurs, DFSP has a locally aggressive behavior with a high recurrence rate. In the head and neck area, resection involving a wide margin of healthy tissue can be difficult because of functional and cosmetic considerations. We describe a novel reconstructive method for half forehead defects with an innovative single local wide scalp flap following excision of DFSP with a 3 cm margin of healthy tissue. Methods Two patients underwent wide resection of forehead DFSP and reconstruction with a single rotational scalp flap. The scalp flap blood supply was provided from three main vessels: the superficial temporal artery, occipital artery and posterior auricular artery. Results No early or late complications were observed in either patient with no local recurrence after 18 months of follow-up. The donor area could be closed primarily in both cases and the flaps survived completely. Conclusion This innovative technique allowed a radical excision of forehead DFSP with sufficient healthy margins, thus potentially decreasing tumor recurrence rate. Reconstruction was achieved avoiding microsurgery, skin expanders and large skin grafts. Moreover, all main reconstructive criteria, such as functional and cosmetic tissue characteristics, were completely fulfilled. PMID:22559860

Risk factors for positive resection margins of breast cancer tumorectomy specimen following breast-conserving surgery.

PubMed

Heiss, Niko; Rousson, Valentin; Ifticene-Treboux, Assia; Lehr, Hans-Anton; Delaloye, Jean-François

2017-12-09

Background The aim of the study was to identify risk factors for positive surgical margins in breast-conserving surgery for breast cancer and to evaluate the influence of surgical experience in obtaining complete resection. Methods All lumpectomies for invasive breast carcinoma and ductal carcinoma in situ (DCIS) between April 2008 and March 2010 were selected from the database of a single institution. Re-excision rates for positive margins as well as patient and histopathologic tumor characteristics were analyzed. Surgical experience was staged by pairs made of Resident plus Specialist or Consultant. Two periods were defined. During period A, the majority of operations were performed by Residents under supervision of Specialist or Consultant. During period B, only palpable tumors were operated by Residents. Results The global re-excision rate was 27% (50 of 183 patients). The presence of DCIS increased the risk for positive margins: 60% (nine of 15 patients) in the case of sole DCIS compared to 26% (41 of 160 patients) for invasive cancer (p = 0.005) and 35% (42 of 120 patients) in the case of peritumoral DCIS compared to 11% (seven of 62 patients) in the case of sole invasive cancer (p = 0.001). Re-excision rate decreased from 36% (23 of 64 patients) during period A to 23% (27 of 119 patients) during period B (p = 0.055). There was no significant difference between the surgical pairs. Conclusion In our study, DCIS was the only risk factor for positive surgical margins. Breast-conserving surgery for non-palpable tumors should be performed by Specialists, however, palpable tumors can be safely operated by Residents under supervision.

Significance of pathological positive superior mesenteric/portal venous invasion in pancreatic cancer.

PubMed

Tewari, Mallika

2016-12-01

Pancreaticoduodenectomy with superior mesenteric/portal venous resection for pancreatic ductal adenocarcinoma (PDAC) is frequently performed with no added morbidity or mortality in case of tumor abutment to the superior mesenteric or portal vein so as to obtain a margin negative resection. True histopathological portal vein invasion is found only in a small subset of such patients. The aim of this review aimed to discuss the significance of histopathological venous invasion in PDAC. For this review available data was searched from PubMed and analyzed. No randomized trials have been published on this topic. Existing data on prognostic factors in histopathological venous invasion by PDAC are limited and recent studies indicate worse survival in this subgroup of patients. In addition, venous invasion in PDAC has been associated with large tumors, involved lymph nodes, perineural invasion and R1 resection. The survival of patients with portal venous resection but without histologic venous invasion is reportedly better than those with histopathological venous invasion; though conflicting studies do exist on the subject. Some studies also relate the depth of venous invasion to prognosis after surgical resection of PDAC. Frank/'histopathological' invasion of superior mesenteric/portal venous and R1 resection indicate a very poor survival. Such patients may be given the opportunity of benefit of neoadjuvant treatment.

Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer.

PubMed

Kelsen, David P; Winter, Katryn A; Gunderson, Leonard L; Mortimer, Joanne; Estes, Norman C; Haller, Daniel G; Ajani, Jaffer A; Kocha, Walter; Minsky, Bruce D; Roth, Jack A; Willett, Christopher G

2007-08-20

We update Radiation Therapy Oncology Group trial 8911 (USA Intergroup 113), a comparison of chemotherapy plus surgery versus surgery alone for patients with localized esophageal cancer. The relationship between resection type and between tumor response and outcome were also analyzed. The chemotherapy group received preoperative cisplatin plus fluorouracil. Outcome based on the type of resection (R0, R1, R2, or no resection) was evaluated. The main end point was overall survival. Disease-free survival, relapse pattern, the influence of postoperative treatment, and the relationship between response to preoperative chemotherapy and outcome were also evaluated. Two hundred sixteen patients received preoperative chemotherapy, 227 underwent immediate surgery. Fifty-nine percent of surgery only and 63% of chemotherapy plus surgery patients underwent R0 resections (P = .5137). Patients undergoing less than an R0 resection had an ominous prognosis; 32% of patients with R0 resections were alive and free of disease at 5 years, only 5% of patients undergoing an R1 resection survived for longer than 5 years. The median survival rates for patients with R1, R2, or no resections were not significantly different. While, as initially reported, there was no difference in overall survival for patients receiving perioperative chemotherapy compared with the surgery only group, patients with objective tumor regression after preoperative chemotherapy had improved survival. For patients with localized esophageal cancer, whether or not preoperative chemotherapy is administered, only an R0 resection results in substantial long-term survival. Even microscopically positive margins are an ominous prognostic factor. After a R1 resection, postoperative chemoradiotherapy therapy offers the possibility of long-term disease-free survival to a small percentage of patients.

Pleural Dye Marking Using Radial Endobronchial Ultrasound and Virtual Bronchoscopy before Sublobar Pulmonary Resection for Small Peripheral Nodules.

PubMed

Lachkar, Samy; Baste, Jean-Marc; Thiberville, Luc; Peillon, Christophe; Rinieri, Philippe; Piton, Nicolas; Guisier, Florian; Salaun, Mathieu

2018-01-01

Minimally invasive surgery of pulmonary nodules allows suboptimal palpation of the lung compared to open thoracotomy. The objective of this study was to assess endoscopic pleural dye marking using radial endobronchial ultrasound (r-EBUS) and virtual bronchoscopy to localize small peripheral lung nodules immediately before minimally invasive resection. The endoscopic procedure was performed without fluoroscopy, under general anesthesia in the operating room immediately before minimally invasive surgery. Then, 1 mL of methylene blue (0.5%) was instilled into the guide sheath, wedged in the subpleural space. Wedge resection or segmentectomy were guided by visualization of the dye on the pleural surface. Contribution of dye marking to the surgical procedure was rated by the surgeon. Twenty-five nodules, including 6 ground glass opacities, were resected in 22 patients by video-assisted thoracoscopic wedge resection (n = 11) or robotic-assisted thoracoscopic surgery (10 segmentectomies and 1 wedge resection). The median greatest diameter of nodules was 8 mm. No conversion to open thoracotomy was needed. The endoscopic procedure added an average 10 min to surgical resection. The dye was visible on the pleural surface in 24 cases. Histological diagnosis and free margin resection were obtained in all cases. Median skin-to-skin operating time was 90 min for robotic segmentectomy and 40 min for video-assisted wedge resection. The same operative precision was considered impossible by the surgeon without dye marking in 21 cases. Dye marking using r-EBUS and virtual bronchoscopy can be easily and safely performed to localize small pulmonary nodules immediately before minimally invasive resection. © 2018 S. Karger AG, Basel.

Resection followed by stereotactic radiosurgery to resection cavity for intracranial metastases.

PubMed

Do, Ly; Pezner, Richard; Radany, Eric; Liu, An; Staud, Cecil; Badie, Benham

2009-02-01

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. 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. 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. 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.

Preoperative chemoradiation with capecitabine, irinotecan and cetuximab in rectal cancer: significance of pre-treatment and post-resection RAS mutations.

PubMed

Gollins, Simon; West, Nick; Sebag-Montefiore, David; Myint, Arthur Sun; Saunders, Mark; Susnerwala, Shabbir; Quirke, Phil; Essapen, Sharadah; Samuel, Leslie; Sizer, Bruce; Worlding, Jane; Southward, Katie; Hemmings, Gemma; Tinkler-Hundal, Emma; Taylor, Morag; Bottomley, Daniel; Chambers, Philip; Lawrie, Emma; Lopes, Andre; Beare, Sandy

2017-10-24

The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation (CRT) is uncertain. In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen. Eighty-two patients were recruited and 76 underwent surgery, with R0 resection in 67 (82%, 90%CI: 73-88%) (four patients with clinical complete response declined surgery). Twenty-four patients (30%) had an excellent clinical or pathological response (ECPR). Using NGS 24 (46%) of 52 matched biopsies/resections were discrepant: ten patients (19%) gained 13 new resection mutations compared to biopsy (12 KRAS, one PIK3CA) and 18 (35%) lost 22 mutations (15 KRAS, 7 PIK3CA). Tumours only ever testing RAS wild-type had significantly greater ECPR than tumours with either biopsy or resection RAS mutations (14/29 [48%] vs 10/51 [20%], P=0.008), with a trend towards increased overall survival (HR 0.23, 95% CI 0.05-1.03, P=0.055). This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss.

Total mesorectal excision for the treatment of rectal cancer

PubMed Central

Zedan, Ali; Salah, Tareq

2015-01-01

Introduction In the surgical treatment of rectal cancer, a clear circumferential resection margin and distal resection margin should be obtained. The aim of this study was to determine the morbidity, mortality, survival outcome, and local failure after total mesorectal excision (TME) in the surgical treatment of rectal cancer. Methods This retrospective study was conducted on 101 patients treated for rectal cancer using low anterior resection (LAR), abdominoperinial resection (APR), or Hartmaan’s technique. In all operative procedures, total mesorectal excisions (TMEs) were done. The patients were treated from November 2000 to April 2011 in the South Egypt Cancer Institute (SECI) of Assuit University (Egypt). Neo-adjuvant therapy was given to those patients with serosalin filtration, lymph node involvement, and sexual and urinary function impairment. Data were analyzed using IBM-SPSS version 21, and survival rates were estimated using the Kaplan-Meier method. Results One hundred one patients were evaluable (61 males, 40 females). Regarding the operative procedure used, it was: (APR), LAR, Hartmaan’s technique in 15.8%, 71.3%, and 12.9% of patients, respectively. Operation-related mortality during the 30 days after surgery was 3%. The operations resulted in morbidity in 25% of the patients, anastomotic site leak in 5.9% of the patients, urinary dysfynction in 9.9% of the patients, and erectile dysfunction in 15.8% of the male patients. Regarding safety margin, the median distances were distal/radial margin, 23/12 mm, distal limit 7 cm. Median lymph nodes harvest 19 nodes. Primary tumor locations were anteriorly 23.8%, laterally 13.9%, posteriorly 38.6%, and circumferential 23.8%. Protective stoma 16.8%. Primary Tumor TNM classification (T1, T2, T3, and T4; 3, 28.7, 55.4, and 12.9%, respectively). Nodes Metastases (N0, N1, and N2; 57.4, 31.7, and 10.9%, respectively). TNM staging (I, II, III, and IV; 15.8, 29.7, 46.5, and 7.9%, respectively). Chemotherapy was administered to 67.3% of the patients. Radiotherapy (short course neoadjuvant, long course neoadjuvant, and adjuvant postoperative used in 33.7, 20.8, and 19.8% of patients, respectively). Survival 5-years CSS was 73% and 5-years RFS 71%. Mean operative time was 213 minutes. The average amount of intraoperative blood loss was 344 mL. Conclusion Total mesorectal excision (TME) represents the gold-standard technique in rectal cancer surgery. It is safe with neoadjuvent chemoradiotherapy and provides both maximal oncological efficiency (local control and long-term survival and maintenance of a good quality of life). PMID:26816592

Total mesorectal excision for the treatment of rectal cancer.

PubMed

Zedan, Ali; Salah, Tareq

2015-12-01

In the surgical treatment of rectal cancer, a clear circumferential resection margin and distal resection margin should be obtained. The aim of this study was to determine the morbidity, mortality, survival outcome, and local failure after total mesorectal excision (TME) in the surgical treatment of rectal cancer. This retrospective study was conducted on 101 patients treated for rectal cancer using low anterior resection (LAR), abdominoperinial resection (APR), or Hartmaan's technique. In all operative procedures, total mesorectal excisions (TMEs) were done. The patients were treated from November 2000 to April 2011 in the South Egypt Cancer Institute (SECI) of Assuit University (Egypt). Neo-adjuvant therapy was given to those patients with serosalin filtration, lymph node involvement, and sexual and urinary function impairment. Data were analyzed using IBM-SPSS version 21, and survival rates were estimated using the Kaplan-Meier method. One hundred one patients were evaluable (61 males, 40 females). Regarding the operative procedure used, it was: (APR), LAR, Hartmaan's technique in 15.8%, 71.3%, and 12.9% of patients, respectively. Operation-related mortality during the 30 days after surgery was 3%. The operations resulted in morbidity in 25% of the patients, anastomotic site leak in 5.9% of the patients, urinary dysfynction in 9.9% of the patients, and erectile dysfunction in 15.8% of the male patients. Regarding safety margin, the median distances were distal/radial margin, 23/12 mm, distal limit 7 cm. Median lymph nodes harvest 19 nodes. Primary tumor locations were anteriorly 23.8%, laterally 13.9%, posteriorly 38.6%, and circumferential 23.8%. Protective stoma 16.8%. Primary Tumor TNM classification (T1, T2, T3, and T4; 3, 28.7, 55.4, and 12.9%, respectively). Nodes Metastases (N0, N1, and N2; 57.4, 31.7, and 10.9%, respectively). TNM staging (I, II, III, and IV; 15.8, 29.7, 46.5, and 7.9%, respectively). Chemotherapy was administered to 67.3% of the patients. Radiotherapy (short course neoadjuvant, long course neoadjuvant, and adjuvant postoperative used in 33.7, 20.8, and 19.8% of patients, respectively). Survival 5-years CSS was 73% and 5-years RFS 71%. Mean operative time was 213 minutes. The average amount of intraoperative blood loss was 344 mL. Total mesorectal excision (TME) represents the gold-standard technique in rectal cancer surgery. It is safe with neoadjuvent chemoradiotherapy and provides both maximal oncological efficiency (local control and long-term survival and maintenance of a good quality of life).

Assessment of Clinical Risk Management System in Hospitals: An Approach for Quality Improvement

PubMed Central

Farokhzadian, Jamileh; Nayeri, Nahid Dehghan; Borhani, Fariba

2015-01-01

Background: Clinical risks have created major problems in healthcare system such as serious adverse effects on patient safety and enhancing the financial burden for the healthcare. Thus, clinical risk management (CRM) system has been introduced for improving the quality and safety of services to health care. The aim of this study was to assess the status of CRM in the hospitals. Methods: A cross-sectional study was conducted on 200 nursing staff from three teaching hospitals affiliated with the Kerman University of Medical Sciences in southeast of Iran. Data were collected from the participants using questionnaire and observational checklist in quality improvement offices and selected wards. The data were analyzed using SPSS version 20. Results: Almost, 57% of persons participated in at least one of training sessions on CRM. The status of CRM system was rated from weak to moderate (2.93±0.72- 3.18±0.66). Among the six domains of CRM system, the highest mean belonged to domain the monitoring of analysis, evaluation and risk control (3.18±0.72); the lowest mean belonged to domain the staff’s knowledge, recognition and understanding of CRM (2.93±0.66). There were no integrated electronic systems for recording and analyzing clinical risks and incidents in the hospitals. Conclusion: Attempts have been made to establish CRM through improvement quality approach such as clinical governance and accreditation, but not enough, however, health care should move toward quality improvement and safe practice through the effective integration of CRM in organizational process. PMID:26156927

Nuclear Export Factor CRM1 Interacts with Nonstructural Proteins NS2 from Parvovirus Minute Virus of Mice

PubMed Central

Bodendorf, Ursula; Cziepluch, Celina; Jauniaux, Jean-Claude; Rommelaere, Jean; Salomé, Nathalie

1999-01-01

The nonstructural NS2 proteins of autonomous parvoviruses are known to act in a host cell-dependent manner and to play a role in viral DNA replication, efficient translation of viral mRNA, and/or encapsidation. Their exact function during the parvovirus life cycle remains, however, still obscure. We report here the characterization of the interaction with the NS2 proteins from the parvovirus minute virus of mice (MVM) and rat as well as mouse homologues of the human CRM1 protein, a member of the importin-beta family recently identified as an essential nuclear export factor. Using the two-hybrid system, we could detect the interaction between the carboxy-terminal region of rat CRM1 and each of the three isoforms of NS2 (P [or major], Y [or minor], and L [or rare]). NS2 proteins were further shown to interact with the full-length CRM1 by coimmunoprecipitation experiments using extracts from both mouse and rat cell lines. Our data show that CRM1 preferentially binds to the nonphosphorylated isoforms of NS2. Moreover, we observed that the treatment of MVM-infected cells with leptomycin B, a drug that specifically inhibits the CRM1-dependent nuclear export pathway, leads to a drastic accumulation of NS2 proteins in the nucleus. Both NS2 interaction with CRM1 and nuclear accumulation upon leptomycin B treatment strongly suggest that these nonstructural viral proteins are actively exported out of the nuclei of infected cells via a CRM1-mediated nuclear export pathway. PMID:10438867

14 CFR 121.427 - Recurrent training.

Code of Federal Regulations, 2011 CFR

2011-01-01

... required by §§ 121.421(b) and 121.422(b), respectively. (4) Approved recurrent CRM training. For flight... operational flight training (LOFT) session. The recurrent CRM training requirement does not apply until a person has completed the applicable initial CRM training required by §§ 121.419, 121.421, or 121.422. (c...

Contrasting Norm Referenced and Criterion Referenced Measures.

ERIC Educational Resources Information Center

Randall, Robert S.

Differences in design between norm referenced measures (NRM) and criterion referenced measures (CRM) are reviewed, and some of the procedures proposed on designing and evaluating CRM are examined. Differences in design of NRM and CRM are said to arise from the different purposes that underlie each measure. In addition, there are differences among…

28 CFR 16.91 - Exemption of Criminal Division Systems-limited access, as indicated.

Code of Federal Regulations, 2010 CFR

2010-07-01

...: (1) Central Criminal Division, Index File and Associated Records System of Records (JUSTICE/CRM-001... System of Records (JUSTICE/CRM-004)—Limited Access. These exemptions apply to the extent that information... Security File System of Records(JUSTICE/CRM-002). These exemptions apply to the extent that information in...

14 CFR 121.427 - Recurrent training.

Code of Federal Regulations, 2010 CFR

2010-01-01

... required by §§ 121.421(b) and 121.422(b), respectively. (4) Approved recurrent CRM training. For flight... operational flight training (LOFT) session. The recurrent CRM training requirement does not apply until a person has completed the applicable initial CRM training required by §§ 121.419, 121.421, or 121.422. (c...

Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults.

PubMed

Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca

2010-04-01

This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

Concordance of gross surgical and final fixed margins in vulvar intraepithelial neoplasia 3 and vulvar cancer.

PubMed

DeSimone, Christopher P; Crisp, Meredith P; Ueland, Frederick R; DePriest, Paul D; van Nagell, John R; Lele, Subodh M; Modesitt, Susan C

2006-08-01

To prospectively evaluate the concordance of initial surgical vulvar margins and final fixed margins and to determine the amount of microscopic pathology of grossly negative margins in women with vulvar intraepithelial neoplasia (VIN) 3 or vulvar carcinoma. Women with VIN 3 or vulvar carcinoma undergoing surgical excision were identified. Prior to excision, acetic acid was used to highlight the lesions, and 2 sutures were placed, 1 at the edge of gross disease and another 1 cm distal from the first. After specimen removal and fixation, the distance between sutures and microscopic involvement of VIN was determined. Twenty-seven women were enrolled; however, only 19 had final fixed specimens that could be accurately measured. The median fixed distance of the vulvar margin was 0.85 cm (mean, 0.83; SD, 0.19) as compared to the gross, 1-cm margin (p = 0.001). Three subjects (16%) had microscopic involvement by VIN 3 in the grossly negative epithelium between the 2 sutures, but none had a positive peripheral margin. The gross surgical margin after vulvar resection is reduced by 15% when measured in its final fixed state, and a grossly negative 1-cm margin will seldom harbor significant disease.

Application of the 226Ra– 230Th– 234U and 227Ac– 231Pa– 235U radiochronometers to uranium certified reference materials

DOE PAGES

Rolison, John M.; Treinen, Kerri C.; McHugh, Kelly C.; ...

2017-11-06

Uranium certified reference materials (CRM) issued by New Brunswick Laboratory were subjected to dating using four independent uranium-series radiochronometers. In all cases, there was acceptable agreement between the model ages calculated using the 231Pa– 235U, 230Th– 234U, 227Ac– 235U or 226Ra– 234U radiochronometers and either the certified 230Th– 234U model date (CRM 125-A and CRM U630), or the known purification date (CRM U050 and CRM U100). Finally, the agreement between the four independent radiochronometers establishes these uranium certified reference materials as ideal informal standards for validating dating techniques utilized in nuclear forensic investigations in the absence of standards with certifiedmore » model ages for multiple radiochronometers.« less

Application of the 226Ra– 230Th– 234U and 227Ac– 231Pa– 235U radiochronometers to uranium certified reference materials

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

Rolison, John M.; Treinen, Kerri C.; McHugh, Kelly C.

Uranium certified reference materials (CRM) issued by New Brunswick Laboratory were subjected to dating using four independent uranium-series radiochronometers. In all cases, there was acceptable agreement between the model ages calculated using the 231Pa– 235U, 230Th– 234U, 227Ac– 235U or 226Ra– 234U radiochronometers and either the certified 230Th– 234U model date (CRM 125-A and CRM U630), or the known purification date (CRM U050 and CRM U100). Finally, the agreement between the four independent radiochronometers establishes these uranium certified reference materials as ideal informal standards for validating dating techniques utilized in nuclear forensic investigations in the absence of standards with certifiedmore » model ages for multiple radiochronometers.« less

Preparation and provisional certification of NBL Spectrographic Impurity Standards, CRM 123 (1-7) and 124 (1-7)

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

Santoliquido, P.M.

This report describes the design, production, and provisional certification of two new certified reference materials (CRMs): CRM No. 123 (1-7), U/sub 3/O/sub 8/ containing 18 trace elements, and CRM No. 124 (1-7), U/sub 3/O/sub 8/ containing 24 trace elements. The elements to be included and concentrations to be used were decided on the basis of information gathered from users of a previous CRM of this type, CRM No. 98 (1-7). The new CRMs were prepared by the addition of trace elements to high purity U/sub 3/O/sub 8/. Provisional certification was accomplished by an interlaboratory program in which four different laboratoriesmore » analyzed the materials by carrier distillation dc arc emission spectrography.« less

Technical Considerations for Red Marking Ink Use When Interpreting Specimen Radiographs: Case Report.

PubMed

Brice, Matthew E; Gossweiler, Marisa; Bennett, Larry

2017-03-01

Artifacts are universal across all imaging modalities, varying in their conspicuity and significance. In this report three patients with pathology-proven breast cancer who had densities masquerading as microcalcifications at the resection margins of the lumpectomy specimens, but had negative microscopic margins, will be discussed. It was determined that these pseudocalcifications were the result of ink precipitates from a commonly utilized tissue marking dye. This artifact was further evaluated and reproduced by utilizing a boneless chicken breast as a phantom. © RSNA, 2016.

[Pathoanatomical preparation and reporting for dysplasias and cancers of the cervix uteri: cervical biopsy, conization, radical hysterectomy and exenteration].

PubMed

Horn, L-C; Einenkel, J; Höckel, M; Kölbl, H; Kommoss, F; Lax, S F; Reich, O; Riethdorf, L; Schmidt, D

2007-07-01

A careful macroscopic description with selection of representative tissue for histological examination is required for quality assurance, for assessing prognostic factors and for answering legal questions in (pre)cancerous lesions of the cervix uteri. Exact and standardized gross inspection and preparation are decisive for the quality of the histopathological statement. The extent of cervical carcinomas should be given in three dimensions, including the relative depth of invasion into the cervical wall. The report should include size, type (according to the WHO classification) and grading of the tumor, the presence of lymphatic as well as blood vessel invasion and perineural involvement. The statement for resection margins should include the vaginal, parametrial, rectal and vesical directions. It is also mandatory to document the number of lymph nodes with metastatic disease in relation to the total number of nodes investigated. The staging should follow the TNM system. In the handling of conisation specimens, it is important to appropriately document localization, horizontal expansion, depth of invasion including microinvasion of any dysplastic or malignant lesions. Clockwise dissection of the conisation specimen, total submission, and step sections are recommended. The preparation of exenteration specimens is a highly skilled job: the exact tumor dimension should be given in its relation to all resected organs and structures with special focus on resection margins.

Simulation of Boundary-Layer Cumulus and Stratocumulus Clouds using a Cloud-Resolving Model With Low- and Third-Order Turbulence Closures

NASA Technical Reports Server (NTRS)

Xu, Kuan-Man; Cheng, Anning

2007-01-01

The effects of subgrid-scale condensation and transport become more important as the grid spacings increase from those typically used in large-eddy simulation (LES) to those typically used in cloud-resolving models (CRMs). Incorporation of these effects can be achieved by a joint probability density function approach that utilizes higher-order moments of thermodynamic and dynamic variables. This study examines how well shallow cumulus and stratocumulus clouds are simulated by two versions of a CRM that is implemented with low-order and third-order turbulence closures (LOC and TOC) when a typical CRM horizontal resolution is used and what roles the subgrid-scale and resolved-scale processes play as the horizontal grid spacing of the CRM becomes finer. Cumulus clouds were mostly produced through subgrid-scale transport processes while stratocumulus clouds were produced through both subgrid-scale and resolved-scale processes in the TOC version of the CRM when a typical CRM grid spacing is used. The LOC version of the CRM relied upon resolved-scale circulations to produce both cumulus and stratocumulus clouds, due to small subgrid-scale transports. The mean profiles of thermodynamic variables, cloud fraction and liquid water content exhibit significant differences between the two versions of the CRM, with the TOC results agreeing better with the LES than the LOC results. The characteristics, temporal evolution and mean profiles of shallow cumulus and stratocumulus clouds are weakly dependent upon the horizontal grid spacing used in the TOC CRM. However, the ratio of the subgrid-scale to resolved-scale fluxes becomes smaller as the horizontal grid spacing decreases. The subcloud-layer fluxes are mostly due to the resolved scales when a grid spacing less than or equal to 1 km is used. The overall results of the TOC simulations suggest that a 1-km grid spacing is a good choice for CRM simulation of shallow cumulus and stratocumulus.

A Scalable Cloud Library Empowering Big Data Management, Diagnosis, and Visualization of Cloud-Resolving Models

NASA Astrophysics Data System (ADS)

Zhou, S.; Tao, W. K.; Li, X.; Matsui, T.; Sun, X. H.; Yang, X.

2015-12-01

A cloud-resolving model (CRM) is an atmospheric numerical model that can numerically resolve clouds and cloud systems at 0.25~5km horizontal grid spacings. The main advantage of the CRM is that it can allow explicit interactive processes between microphysics, radiation, turbulence, surface, and aerosols without subgrid cloud fraction, overlapping and convective parameterization. Because of their fine resolution and complex physical processes, it is challenging for the CRM community to i) visualize/inter-compare CRM simulations, ii) diagnose key processes for cloud-precipitation formation and intensity, and iii) evaluate against NASA's field campaign data and L1/L2 satellite data products due to large data volume (~10TB) and complexity of CRM's physical processes. We have been building the Super Cloud Library (SCL) upon a Hadoop framework, capable of CRM database management, distribution, visualization, subsetting, and evaluation in a scalable way. The current SCL capability includes (1) A SCL data model enables various CRM simulation outputs in NetCDF, including the NASA-Unified Weather Research and Forecasting (NU-WRF) and Goddard Cumulus Ensemble (GCE) model, to be accessed and processed by Hadoop, (2) A parallel NetCDF-to-CSV converter supports NU-WRF and GCE model outputs, (3) A technique visualizes Hadoop-resident data with IDL, (4) A technique subsets Hadoop-resident data, compliant to the SCL data model, with HIVE or Impala via HUE's Web interface, (5) A prototype enables a Hadoop MapReduce application to dynamically access and process data residing in a parallel file system, PVFS2 or CephFS, where high performance computing (HPC) simulation outputs such as NU-WRF's and GCE's are located. We are testing Apache Spark to speed up SCL data processing and analysis.With the SCL capabilities, SCL users can conduct large-domain on-demand tasks without downloading voluminous CRM datasets and various observations from NASA Field Campaigns and Satellite data to a local computer, and inter-compare CRM output and data with GCE and NU-WRF.

Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery

PubMed Central

Lee, John Y-K.; Thawani, Jayesh P.; Pierce, John; Zeh, Ryan; Martinez-Lage, Maria; Chanin, Michelle; Venegas, Ollin; Nims, Sarah; Learned, Kim; Keating, Jane; Singhal, Sunil

2016-01-01

Background Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense. Objective To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease. Methods Fifteen patients were identified and administered an FDA-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) prior to surgical resection. An NIR camera was utilized to localize the tumor prior to resection and to visualize surgical margins following resection. Neuropathology and MR imaging data were used to assess the accuracy and precision of NIR-fluorescence in identifying tumor tissue. Results NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12/15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with SBR (P = .03). Non-enhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71). Conclusion Using Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity. PMID:27741220

Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.

PubMed

Cainap, Calin; Nagy, Viorica; Seicean, Andrada; Gherman, Alexandra; Laszlo, Istvan; Lisencu, Cosmin; Nadim, Al Hajar; Constantin, Anne-Marie; Cainap, Simona

2016-01-01

The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

Adrenocortical carcinoma with inferior vena cava, left renal vein and right atrium tumor thrombus extension

PubMed Central

Annamaria, Pronio; Silvia, Piroli; Bernardo, Ciamberlano; Alessandro, De Luca; Antonino, Marullo; Antonio, Barretta; Giuseppe, Mazzesi; Massimo, Rossi; Montesani, Chiara

2015-01-01

Introduction Adrenocortical carcinoma (ACC) is a rare, but highly aggressive type of tumor with an annual incidence of 1–2 cases per million. The prognosis is poor with a five-year overall survival rate of ∼35%. The poor prognosis may be related to the advanced stage at which the majority of ACCs are detected. Complete surgical resection remains the most effective treatment. Presentation of the case A 51-year-old female patient with recent onset of dyspepsia, ascites and peripheral edema was referred to our institution. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) displayed a 8 cm Ø right adrenal mass. Moreover a tumor thrombus jutted out into the IVC, left renal vein and right atrium. An echocardiographic evaluation confirmed the presence of the tumor thrombus in the right atrium. The patient underwent adrenalectomy with removal of its intravascular extension with the assistance of cardiopulmonary bypass and hypothermia. Discussion ACC is a rare malignancy and ACC with tumor thrombus extension is a rare presentation. Patients can present with a variety of sign and symptoms, depending on the extent of the tumor. CT scan of chest and abdomen represents the gold standard in ACC staging while magnetic resonance imaging (MRI) is preferred for tumor thrombus characterization. Complete surgical resection with a negative margin, R0 resection, is the only curative option for localized disease. Kidney sparing surgery should be performed when possible. Conclusion We present a rare case of Adrenocortical carcinoma with tumor thrombus extending into the IVC and right atrium. Complete resection with negative margins represents the best therapeutic chance for these patients. PMID:26355237

Adrenocortical carcinoma with inferior vena cava, left renal vein and right atrium tumor thrombus extension.

PubMed

Annamaria, Pronio; Silvia, Piroli; Bernardo, Ciamberlano; Alessandro, De Luca; Antonino, Marullo; Antonio, Barretta; Giuseppe, Mazzesi; Massimo, Rossi; Montesani, Chiara

2015-01-01

Adrenocortical carcinoma (ACC) is a rare, but highly aggressive type of tumor with an annual incidence of 1-2 cases per million. The prognosis is poor with a five-year overall survival rate of ∼35%. The poor prognosis may be related to the advanced stage at which the majority of ACCs are detected. Complete surgical resection remains the most effective treatment. A 51-year-old female patient with recent onset of dyspepsia, ascites and peripheral edema was referred to our institution. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) displayed a 8cm Ø right adrenal mass. Moreover a tumor thrombus jutted out into the IVC, left renal vein and right atrium. An echocardiographic evaluation confirmed the presence of the tumor thrombus in the right atrium. The patient underwent adrenalectomy with removal of its intravascular extension with the assistance of cardiopulmonary bypass and hypothermia. ACC is a rare malignancy and ACC with tumor thrombus extension is a rare presentation. Patients can present with a variety of sign and symptoms, depending on the extent of the tumor. CT scan of chest and abdomen represents the gold standard in ACC staging while magnetic resonance imaging (MRI) is preferred for tumor thrombus characterization. Complete surgical resection with a negative margin, R0 resection, is the only curative option for localized disease. Kidney sparing surgery should be performed when possible. We present a rare case of Adrenocortical carcinoma with tumor thrombus extending into the IVC and right atrium. Complete resection with negative margins represents the best therapeutic chance for these patients. Copyright © 2015. Published by Elsevier Ltd.

Additive endoscopic resection may be sufficient for patients with a positive lateral margin after endoscopic resection of early gastric cancer.

PubMed

Kim, Hae Won; Kim, Jie-Hyun; Park, Jun Chul; Jeon, Mi Young; Lee, Yong Chan; Lee, Sang Kil; Shin, Sung Kwan; Chung, Hyun Soo; Noh, Sung Hoon; Kim, Jong Won; Choi, Seung Ho; Park, Jae Jun; Youn, Young Hoon; Park, Hyojin

2017-11-01

No well-established treatment strategies exist for lateral margin positivity (LM+) alone after endoscopic resection (ER) of early gastric cancer (EGC). Thus, we aimed to clarify a treatment strategy for non-curative resection (non-CR) with LM+ alone after ER in EGC. Among 2065 patients with EGC treated by ER, 76 (3.6%) with only LM+ after non-CR of EGC were reviewed retrospectively. Of these, 28 underwent gastrectomy, 25 underwent argon plasma coagulation (APC), and 23 underwent repeat ER (re-ER). We analyzed the clinicopathologic characteristics of all patients and compared those who underwent additive surgery, APC, or re-ER. Of the 76 patients, 28 (36.8%) fulfilled the absolute criteria and 48 (63.2%) the expanded criteria for ER. Among the latter patients, the proportion undergoing additive surgery was 75.0%, higher than that of patients in the former group (P = .014). Residual cancer cells were observed in 70.6% of patients after additive surgery or re-ER. Residual cancer cells were observed significantly more often in patients with undifferentiated-type than in those with differentiated-type EGC (P = .02). However, no lymph node metastasis was observed in any patient after additive surgery. Our results suggest that endoscopic treatment may be a sufficient additive therapy for patients with LM+ alone after ER, irrespective of whether the absolute or expanded ER criteria are used. However, as complete ablation of remnant cells cannot be guaranteed, re-ER is a better additive treatment than APC. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck.

PubMed

Weiss, Jared M; Grilley-Olson, Juneko E; Deal, Allison Mary; Zevallos, Jose P; Chera, Bhishamjit S; Paul, Jennifer; Knowles, Mary Fleming; Usenko, Dmitriy; Weissler, Mark C; Patel, Samip; Hayes, David N; Hackman, Trevor

2018-05-09

The objective of this study was to demonstrate the feasibility and efficacy of induction chemotherapy, surgery, and pathology-guided adjuvant therapy to treat transorally resectable squamous head and neck cancer. Patients had squamous head and neck cancer that was resectable by the transoral route and advanced-stage disease (American Joint Committee on Cancer stage III-IV, T3-T4 tumors, and/or positive lymph nodes). They received treatment with weekly carboplatin at an area under the curve of 2, plus paclitaxel 135 mg/m 2 , and daily lapatinib 1000mg for 6 weeks followed by surgical resection. Pathology that revealed margins <5 mm, extracapsular extension, N2a of N2b lymph node status, perineural invasion, or lymphovascular space invasion resulted in adjuvant radiotherapy concurrent with weekly cisplatin. Pathology with N2c/N3 lymph node status or positive margins resulted in radiation with bolus cisplatin. The primary endpoint was the clinical response rate to induction chemotherapy, and a key secondary endpoint was feasibility. Toxicity was modest, and 37 of 40 patients completed study procedures as planned. The clinical response rate was 93%, the pathologic complete response rate was 36%, and the clinical response did not predict for a pathologic complete response. No patient on study follow-up has recurred or died. Twenty-nine of 39 patients who underwent surgery avoided radiation. Speech and swallowing function were well preserved. The study met both its primary efficacy endpoint and the secondary feasibility endpoint. Neoadjuvant, systemic therapy and surgical resection followed by risk-adapted adjuvant therapy resulted in high response rates and excellent long-term outcomes and should be further studied. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Identifying Clinical Factors Which Predict for Early Failure Patterns Following Resection for Pancreatic Adenocarcinoma in Patients Who Received Adjuvant Chemotherapy Without Chemoradiation.

PubMed

Walston, Steve; Salloum, Joseph; Grieco, Carmine; Wuthrick, Evan; Diaz, Dayssy A; Barney, Christian; Manilchuk, Andrei; Schmidt, Carl; Dillhoff, Mary; Pawlik, Timothy M; Williams, Terence M

2018-05-04

The role of radiation therapy (RT) in resected pancreatic cancer (PC) remains incompletely defined. We sought to determine clinical variables which predict for local-regional recurrence (LRR) to help select patients for adjuvant RT. We identified 73 patients with PC who underwent resection and adjuvant gemcitabine-based chemotherapy alone. We performed detailed radiologic analysis of first patterns of failure. LRR was defined as recurrence of PC within standard postoperative radiation volumes. Univariate analyses (UVA) were conducted using the Kaplan-Meier method and multivariate analyses (MVA) utilized the Cox proportional hazard ratio model. Factors significant on UVA were used for MVA. At median follow-up of 20 months, rates of local-regional recurrence only (LRRO) were 24.7%, LRR as a component of any failure 68.5%, metastatic recurrence (MR) as a component of any failure 65.8%, and overall disease recurrence (OR) 90.5%. On UVA, elevated postoperative CA 19-9 (>90 U/mL), pathologic lymph node positive (pLN+) disease, and higher tumor grade were associated with increased LRR, MR, and OR. On MVA, elevated postoperative CA 19-9 and pLN+ were associated with increased MR and OR. In addition, positive resection margin was associated with increased LRRO on both UVA and MVA. About 25% of patients with PC treated without adjuvant RT develop LRRO as initial failure. The only independent predictor of LRRO was positive margin, while elevated postoperative CA 19-9 and pLN+ were associated with predicting MR and overall survival. These data may help determine which patients benefit from intensification of local therapy with radiation.

Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?

PubMed Central

Merchant, Nipun B; Rymer, Jennifer; Koehler, Elizabeth AS; Ayers, G Daniel; Castellanos, Jason; Kooby, David A; Weber, Sharon H; Cho, Clifford S; Schmidt, C Max; Nakeeb, Atilla; Matos, Jesus M; Scoggins, Charles R; Martin, Robert CG; Kim, Hong Jin; Ahmad, Syed A; Chu, Carrie K; McClaine, Rebecca; Bednarski, Brian K; Staley, Charles A; Sharp, Kenneth; Parikh, Alexander A

2014-01-01

BACKGROUND The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients. STUDY DESIGN Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown. RESULTS There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n = 374) and those receiving adjuvant CRT (n = 299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p = 0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN-negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p = 0.034). CONCLUSIONS This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival. PMID:19476845

Probe-based confocal laser endomicroscopy in the margin delineation of early gastric cancer for endoscopic submucosal dissection.

PubMed

Park, Jun Chul; Park, Yehyun; Kim, Hyun Ki; Jo, Jeong-Hyeon; Park, Chan Hyuk; Kim, Eun Hye; Jung, Da Hyun; Chung, Hyunsoo; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan

2017-05-01

We evaluated probe-based confocal laser endomicroscopy (pCLE) in the margin delineation of early gastric cancer (EGC) for endoscopic submucosal dissection in comparison with white-light imaging with chromoendoscopy (CE). We conducted a prospective, randomized controlled study from November 2013 to October 2014 in a tertiary referral hospital. A total of 101 patients scheduled for endoscopic submucosal dissection due to differentiated EGC were randomized into pCLE and CE groups (pCLE 51, CE 50). Markings were made by electrocautery at the proximal and distal tumor margins, as determined by either pCLE or CE. The distance from the marking to the tumor margin was measured in the resected specimen histopathologically and was compared between the two groups by a linear mixed model. Among 104 lesions, 80 lesions with 149 markings (pCLE 68, CE 81) were analyzed after excluding undifferentiated EGCs (n = 8) and unidentifiable markings (n = 13). Although the complete resection rate showed no difference between the groups (94.6% vs 93.2%, P = 1.000), the median distance from the marking to the margin was shorter in the pCLE group (1.3 vs 1.8 mm, P = 0.525) and the proportion of the distance <1 mm was higher (43.9% vs 27.6%, P = 0.023) in the pCLE group. Finally, subgroup analysis with superficial flat lesions (18 lesions, 31 marking dots) showed a significantly decreased distance in the pCLE group (0.5 vs 3.1 mm, P = 0.007). Among EGCs with superficial flat morphology, in which the accurate evaluation of lateral extent is difficult with CE, pCLE would be useful for more precise margin delineation. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Differential Impact of Close Surgical Margin on Local Recurrence According to Primary Tumor Size in Oral Squamous Cell Carcinoma.

PubMed

Jang, Jeon Yeob; Choi, Nayeon; Ko, Young-Hyeh; Chung, Man Ki; Son, Young-Ik; Baek, Chung-Hwan; Baek, Kwan-Hyuck; Jeong, Han-Sin

2017-06-01

The extent of surgical safety margin (gross tumor border to resection margin) in oral cancer surgery remains unclear, and no study has determined the differential impact of close surgical margin and microscopic extension according to primary tumor size in oral cancers. We retrospectively analyzed the clinical data of 325 patients with surgically treated oral cavity squamous cell carcinomas to determine the effect of a close surgical margin (<5 mm) (cSM 5 ) on local recurrence. In addition, the depth of microscopic tumor infiltration was determined in 90 available surgical specimens. The cSM 5 was not related to the risk of local tumor recurrence in early-stage oral cancer, while it significantly increased the rate of local tumor recurrence in resectable advanced-stage oral cancers (hazard ratio 3.157, 95 % confidence interval 1.050-9.407, p = 0.041). Addition of postoperative adjuvant radiation to early-stage tumors with cSM 5 did not further reduce the local recurrence rate compared to surgery alone. The depth of microscopic tumor extension from the gross tumor border was significantly associated with primary tumor thickness (ρ = 0.390, p < 0.001) and tumor sizes (ρ = 0.308, p = 0.003), which was a median (range) of 0.84 (0.14-2.32) mm in T1, 1.06 (0.20-4.34) mm in T2, and 1.77 (0.13-4.70) mm in T3-4. The cSM 5 was a significant risk factor for local recurrence only in advanced oral cancers, but not in early-stage tumors, where microscopic tumor extension was not beyond 3 mm in T1 tumors. Thus, the extent of surgical safety margin can be redefined according to the primary tumor size.

Treatment modalities in sinonasal undifferentiated carcinoma: an analysis from the national cancer database.

PubMed

Khan, Mohemmed N; Konuthula, Neeraja; Parasher, Arjun; Genden, Eric M; Miles, Brett A; Govindaraj, Satish; Iloreta, Alfred M

2017-02-01

Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of unknown etiology with a poor overall prognosis. Its relative rarity has made it difficult to determine the impact of different treatment modalities on survival. Retrospective study of cases in the National Cancer Data Base (NCDB). NCDB cases that were diagnosed as having SNUC between January 1, 2004, and December 31, 2013 were included in the analysis. Outcomes of patients treated with surgery followed adjuvant chemoradiotherapy were compared with definitive chemoradiotherapy. A 5-year survival rate of 42.2% was observed in the 460 patients in the analysis. American Joint Committee on Cancer (AJCC) clinical staging data were available for 304 patients. Of these patients, 60.2% had advanced tumors (AJCC stage 3 or 4). Surgery followed by adjuvant chemoradiotherapy was associated with better survival than definitive chemoradiotherapy (55.8% vs 42.6%, p = 0.007) in the study population. However, in late-stage tumors, there was no difference in survival between the 2 treatment groups (p = 0.22). For late-stage tumors, the time to initiation of adjuvant therapy was 49.2 ± 5.1 days for the surgery plus adjuvant therapy group as compared with 25.9 ± 2.6 days in the definitive chemoradiotherapy group (p < 0.0001), yet this did not appear to affect outcomes. No differences in age, gender, race, Charlson-Deyo score, facility type (academic vs nonacademic), or radiation dose were found between the 2 treatment groups (p > 0.05). Margin status played a critical role in the success of surgical resection, as no patients with positive margin status receiving adjuvant therapy survived to 5 years. Surgery may play a role in a multimodality approach to treatment of late-stage SNUC if the tumor is amenable to surgical resection and negative margins can be reliably obtained. However, in cases where there may be difficulty obtaining negative margins, or this is considered unlikely preoperatively, surgical resection does not appear to provide any additional survival benefit. © 2016 ARS-AAOA, LLC.

78 FR 12234 - Promotions and Incentive Programs for First-Class Mail and Standard Mail

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

...] (BRM) or Courtesy Reply Mail TM (CRM) card or letter bearing a qualifying Intelligent Mail[supreg... mechanism for their customers and to keep the BRM/ CRM envelopes in their outgoing mail pieces by providing a financial benefit when the BRM/CRM envelopes are used. Registration is January 15 to March 31...

Customer Relationship Management in Higher Education: Using Information Systems to Improve the Student-School Relationship

ERIC Educational Resources Information Center

Seeman, Elaine D.; O'Hara, Margaret

2006-01-01

Purpose: The purpose of this paper is to explore customer relationship management (CRM) in a higher education setting. Design/methodology/approach: The development and implementation of a CRM project in a state community college was examined as were the benefits realized by implementing CRM. As colleges increasingly embrace distance learning and…

Adapting Criterion-Referenced Measurement to Individualization of Instruction for Handicapped Children: Some Issues and a First Attempt.

ERIC Educational Resources Information Center

Proger, Barton B.; And Others

Criterion-referenced measurement (CRM) has received increasing attention in regular education. However, it is in education for handicapped children that CRM's flexibility for individualization of both instruction and evaluation become even more fully realized. Research is described on one of the first CRM systems (Individual Achievement Monitoring…

Exploring Use of the Coordinate Response Measure in a Multitalker Babble Paradigm

ERIC Educational Resources Information Center

Humes, Larry E.; Kidd, Gary R.; Fogerty, Daniel

2017-01-01

Purpose: Three experiments examined the use of competing coordinate response measure (CRM) sentences as a multitalker babble. Method: In Experiment I, young adults with normal hearing listened to a CRM target sentence in the presence of 2, 4, or 6 competing CRM sentences with synchronous or asynchronous onsets. In Experiment II, the condition with…

Management training for cockpit crews at Piedmont flight

NASA Technical Reports Server (NTRS)

Sifford, J. C.

1984-01-01

A brief history of Piedmont Airlines' flight operations is presented. A captain-management seminar conducted regularly by Piedmont is discussed. Piedmont's approach to cockpit resource management (CRM) is reviewed, and the relationship of CRM training to other aspects of flight training is addressed. Future leadership research plans and CRM training is considered along with critical training issues.

The impact of administration of conjugate vaccines containing cross reacting material on Haemophilus influenzae type b antibody responses in infants: A systematic review and meta-analysis of randomised controlled trials.

PubMed

Voysey, Merryn; Sadarangani, Manish; Clutterbuck, Elizabeth; Bolgiano, Barbara; Pollard, Andrew J

2016-07-25

Protein-polysaccharide conjugate vaccines such as Haemophilus influenzae type b (Hib), meningococcal, and pneumococcal vaccine, induce immunological memory and longer lasting protection than plain polysaccharide vaccines. The most common proteins used as carriers are tetanus toxoid (TT) and cross reacting material-197 (CRM), a mutant form of diphtheria toxoid. CRM conjugate vaccines have been reported to suppress antibody responses to co-administered Hib-TT vaccine. We conducted a systematic review and meta-analysis of randomised controlled trials in which infants were randomised to receive meningococcal or pneumococcal conjugate vaccines along with Hib-TT. Trials of licensed vaccines with different carrier proteins were included for group C meningococcal (MenC), quadrivalent ACWY meningococcal (MenACWY), and pneumococcal vaccines. Twenty-three trials were included in the meta-analyses. Overall, administration of MenC-CRM in a 2 or 3 dose schedule resulted in a 45% reduction in Hib antibody concentrations (GMR 0.55, 95% CI 0.49-0.62). MenACWY-CRM boosted Hib antibody responses by 22% (GMR 1.22, 95% CI 1.06-1.41) whilst pneumococcal CRM conjugate vaccines had no impact on Hib antibody responses (GMR 0.91, 95% CI 0.68-1.22). The effect of CRM protein-polysaccharide conjugate vaccines on Hib antibody responses varies greatly between vaccines. Co-administration of a CRM conjugate vaccine can produce either positive or negative effects on Hib antibody responses. These inconsistencies suggest that CRM itself may not be the main driver of variability in Hib responses, and challenge current perspectives on this issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Building a simulation-based crisis resource management course for emergency medicine, phase 1: Results from an interdisciplinary needs assessment survey.

PubMed

Hicks, Christopher M; Bandiera, Glen W; Denny, Christopher J

2008-11-01

Emergency department (ED) resuscitation requires the coordinated efforts of an interdisciplinary team. Human errors are common and have a negative impact on patient safety. Although crisis resource management (CRM) skills are utilized in other clinical domains, most emergency medicine (EM) caregivers currently receive no formal CRM training. The objectives were to compile and compare attitudes toward CRM training among EM staff physicians, nurses, and residents at two Canadian academic teaching hospitals. Emergency physicians (EPs), residents, and nurses were asked to complete a Web survey that included Likert scales and short answer questions. Focus groups and pilot testing were used to inform survey development. Thematic content analysis was performed on the qualitative data set and compared to quantitative results. The response rate was 75.7% (N = 84). There was strong consensus regarding the importance of core CRM principles (i.e., effective communication, team leadership, resource utilization, problem-solving, situational awareness) in ED resuscitation. Problems with coordinating team actions (58.8%), communication (69.6%), and establishing priorities (41.3%) were among factors implicated in adverse events. Interdisciplinary collaboration (95.1%), efficiency of patient care (83.9%), and decreased medical error (82.6%) were proposed benefits of CRM training. Communication between disciplines is a barrier to effective ED resuscitation for 94.4% of nurses and 59.7% of EPs (p = 0.008). Residents reported a lack of exposure to (64.3%), yet had interest in (96.4%) formal CRM education using human patient simulation. Nurses rate communication as a barrier to teamwork more frequently than physicians. EM residents are keen to learn CRM skills. An opportunity exists to create a novel interdisciplinary CRM curriculum to improve EM team performance and mitigate human error.

Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial

PubMed Central

Lähteenmäki, Ritva; Puustinen, Juha; Vahlberg, Tero; Lyles, Alan; Neuvonen, Pertti J; Partinen, Markku; Räihä, Ismo; Kivelä, Sirkka-Liisa

2014-01-01

Aim We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here ‘BZD’) use. Methods A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6 months were noted. Results There were two drop-outs on CRM and one on placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025). Withdrawal symptoms did not differ between the groups. Conclusions Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo. PMID:24286360

Immunological detection of phenylalanine hydroxylase protein in Drosophila melanogaster.

PubMed Central

Silva, F J; Bel, Y; Botella, L M; Cotton, R G; Ferré, J

1992-01-01

A monoclonal antibody raised against monkey liver phenylalanine hydroxylase (PAH) has been used to detect this protein in Drosophila melanogaster. A cross-reacting material (CRM) band of apparent molecular mass 50-52 kDa, equivalent to that deduced for the Drosophila melanogaster PAH protein based on the pah gene cDNA sequence, has been detected. This CRM was analysed throughout development and showed an equivalent pattern to that reported for PAH activity in this insect, with maxima at pupariation and at pharate adult formation. Distribution of this CRM in larval tissues, the haemolymph and the adult body is mainly restricted to the larval fat body and the adult head. Demonstration of this CRM as the PAH protein comes from the correlation between the decreased PAH enzyme activities of two mutant strains and their decreased amounts of CRM by Western blotting. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:1417795

Inhibiting cancer cell hallmark features through nuclear export inhibition.

PubMed

Sun, Qingxiang; Chen, Xueqin; Zhou, Qiao; Burstein, Ezra; Yang, Shengyong; Jia, Da

2016-01-01

Treating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical application. Nuclear export factor chromosomal region maintenance 1 (CRM1; Xpo1 and exportin-1) controls cellular localization and function of numerous proteins that are critical for the development of many cancer hallmarks. The diverse actions of CRM1 are likely to explain the broad ranging anti-cancer potency of CRM1 inhibitors observed in pre-clinical studies and/or clinical trials (phase I-III) on both advanced-stage solid and hematological tumors. In this review, we compare and contrast the mechanisms of action of different CRM1 inhibitors, and discuss the potential benefit of unexplored non-covalent CRM1 inhibitors. This emerging field has uncovered that nuclear export inhibition is well poised as an attractive target towards low-toxicity broad-spectrum potent anti-cancer therapy.

The design and delivery of crew resource management training: exploiting available resources.

PubMed

Salas, E; Rhodenizer, L; Bowers, C A

2000-01-01

Despite widespread acceptance throughout commercial and military settings, crew resource management (CRM) training programs have not escaped doubts about their effectiveness. The current state of CRM training is an example of how an entire body of pertinent research and development has not had the impact on practice that it could. In this paper we outline additional resources (i.e., principles, information, findings, and guidelines) from the team training and training effectiveness research literatures that can be used to improve the design and delivery of CRM training. Some of the resources discussed include knowledge about training effectiveness, training teamwork-related skills, scenario design, and performance measurement. We conclude with a discussion of emerging resources as well as those that need to be developed. The purpose of this paper is to provide the CRM training developer with better access to resources that can be applied to the design and delivery of CRM training programs.

Poxvirus-encoded TNF decoy receptors inhibit the biological activity of transmembrane TNF.

PubMed

Pontejo, Sergio M; Alejo, Ali; Alcami, Antonio

2015-10-01

Poxviruses encode up to four different soluble TNF receptors, named cytokine response modifier B (CrmB), CrmC, CrmD and CrmE. These proteins mimic the extracellular domain of the cellular TNF receptors to bind and inhibit the activity of TNF and, in some cases, other TNF superfamily ligands. Most of these ligands are released after the enzymic cleavage of a membrane precursor. However, transmembrane TNF (tmTNF) is not only a precursor of soluble TNF but also exerts specific pro-inflammatory and immunological activities. Here, we report that viral TNF receptors bound and inhibited tmTNF and describe some interesting differences in their activity against the soluble cytokine. Thus, CrmE, which does not inhibit mouse soluble TNF, could block murine tmTNF-induced cytotoxicity. We propose that this anti-tmTNF effect should be taken into consideration when assessing the role of viral TNF decoy receptors in the pathogenesis of poxvirus.

Toward image guided robotic surgery: system validation.

PubMed

Herrell, Stanley D; Kwartowitz, David Morgan; Milhoua, Paul M; Galloway, Robert L

2009-02-01

Navigation for current robotic assisted surgical techniques is primarily accomplished through a stereo pair of laparoscopic camera images. These images provide standard optical visualization of the surface but provide no subsurface information. Image guidance methods allow the visualization of subsurface information to determine the current position in relationship to that of tracked tools. A robotic image guided surgical system was designed and implemented based on our previous laboratory studies. A series of experiments using tissue mimicking phantoms with injected target lesions was performed. The surgeon was asked to resect "tumor" tissue with and without the augmentation of image guidance using the da Vinci robotic surgical system. Resections were performed and compared to an ideal resection based on the radius of the tumor measured from preoperative computerized tomography. A quantity called the resection ratio, that is the ratio of resected tissue compared to the ideal resection, was calculated for each of 13 trials and compared. The mean +/- SD resection ratio of procedures augmented with image guidance was smaller than that of procedures without image guidance (3.26 +/- 1.38 vs 9.01 +/- 1.81, p <0.01). Additionally, procedures using image guidance were shorter (average 8 vs 13 minutes). It was demonstrated that there is a benefit from the augmentation of laparoscopic video with updated preoperative images. Incorporating our image guided system into the da Vinci robotic system improved overall tissue resection, as measured by our metric. Adding image guidance to the da Vinci robotic surgery system may result in the potential for improvements such as the decreased removal of benign tissue while maintaining an appropriate surgical margin.

The impact of type and number of bowel resections on anastomotic leakage risk in advanced ovarian cancer surgery.

PubMed

Grimm, Christoph; Harter, Philipp; Alesina, Pier F; Prader, Sonia; Schneider, Stephanie; Ataseven, Beyhan; Meier, Beate; Brunkhorst, Violetta; Hinrichs, Jakob; Kurzeder, Christian; Heitz, Florian; Kahl, Annett; Traut, Alexander; Groeben, Harald T; Walz, Martin; du Bois, Andreas

2017-09-01

To identify risk factors for anastomotic leakage (AL) in patients undergoing primary advanced ovarian cancer surgery and to evaluate the prognostic implication of AL on overall survival in these patients. We analyzed our institutional database for primary EOC and included all consecutive patients treated by debulking surgery including any type of full circumferential bowel resection beyond appendectomy between 1999 and 2015. We performed logistic regression models to identify risk factors for AL and log-rank tests and Cox proportional hazards models to evaluate the association between AL and survival. AL occurred in 36/800 (4.5%; 95% confidence interval [3%-6%]) of all patients with advanced ovarian cancer and 36/518 (6.9% [5%-9%]) patients undergoing bowel resection during debulking surgery. One hundred fifty-six (30.1%) patients had multiple bowel resections. In these patients, AL rate per patient was only slightly higher (9.0% [5%-13%]) than in patients with rectosigmoid resection only (6.9% [4%-10%]), despite the higher number of anastomosis. No independent predictive factors for AL were identified. AL was independently associated with shortened overall survival (HR 1.9 [1.2-3.4], p=0.01). In the present study, no predictive pre- and/or intraoperative risk factors for AL were identified. AL rate was mainly influenced by rectosigmoid resection and only marginally increased by additional bowel resections. Copyright © 2017 Elsevier Inc. All rights reserved.

Thick tissue diffusion model with binding to optimize topical staining in fluorescence breast cancer margin imaging

NASA Astrophysics Data System (ADS)

Xu, Xiaochun; Kang, Soyoung; Navarro-Comes, Eric; Wang, Yu; Liu, Jonathan T. C.; Tichauer, Kenneth M.

2018-03-01

Intraoperative tumor/surgical margin assessment is required to achieve higher tumor resection rate in breast-conserving surgery. Though current histology provides incomparable accuracy in margin assessment, thin tissue sectioning and the limited field of view of microscopy makes histology too time-consuming for intraoperative applications. If thick tissue, wide-field imaging can provide an acceptable assessment of tumor cells at the surface of resected tissues, an intraoperative protocol can be developed to guide the surgery and provide immediate feedback for surgeons. Topical staining of margins with cancer-targeted molecular imaging agents has the potential to provide the sensitivity needed to see microscopic cancer on a wide-field image; however, diffusion and nonspecific retention of imaging agents in thick tissue can significantly diminish tumor contrast with conventional methods. Here, we present a mathematical model to accurately simulate nonspecific retention, binding, and diffusion of imaging agents in thick tissue topical staining to guide and optimize future thick tissue staining and imaging protocol. In order to verify the accuracy and applicability of the model, diffusion profiles of cancer targeted and untargeted (control) nanoparticles at different staining times in A431 tumor xenografts were acquired for model comparison and tuning. The initial findings suggest the existence of nonspecific retention in the tissue, especially at the tissue surface. The simulator can be used to compare the effect of nonspecific retention, receptor binding and diffusion under various conditions (tissue type, imaging agent) and provides optimal staining and imaging protocols for targeted and control imaging agent.

Surgical treatment strategy for diabetic forefoot osteomyelitis.

PubMed

Fujii, Miki; Terashi, Hiroto; Yokono, Koichi

2016-03-01

The aim of this study was to propose an appropriate surgical treatment for diabetic forefoot osteomyelitis (DFO) involving ischemia or moderate to severe soft tissue infection. The records of 28 patients with osteomyelitis from 2009 to 2015 were retrospectively studied. All patients had undergone surgery based on preoperative magnetic resonance imaging examinations and histopathological or culture analyses confirming the surgical bone margin. The appropriate surgical margin, crucial factors for early healing, and prognosis after complete resection of osteomyelitis were examined. After healing, patients were followed up to assess prognosis (range 32-1,910 days, median 546 days). The healing rate of nonischemic cases of DFO with negative surgical margins was 100% and that of ischemic cases was 84.6%; the ambulatory rates for both types of cases were 100%. No wound (and/or osteomyelitis) recurrence was observed. Nine new cases of DFO developed in six patients (21.4%; eight were due to vascular stenosis, and one was due to biomechanical changes in the foot. After complete resection of osteomyelitis, preoperative and postoperative C-reactive protein levels and the size of the ulcer were significant predictors of early healing (p < 0.05, 0.01, and 0.05, respectively). The appropriate surgical margin should be set in the area of bone marrow edema, based on magnetic resonance imaging examinations after revascularization. In cases with high preoperative or postoperative C-reactive protein levels, long-term antibiotic therapy is recommended, and surgery should be planned after the C-reactive protein levels decrease, except in emergencies. © 2016 by the Wound Healing Society.

78 FR 46339 - Medicare, Medicaid, and Children's Health Insurance Programs: Announcement of Temporary Moratoria...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

...-crm-510.html . \\10\\ Department of Justice, ``Owners of Miami Home Health Companies Sentenced to Prison in $48 million Health Care Fraud Scheme.'' See http://www.justice.gov/opa/pr/2013/February/13-crm-243... Convicted in Medicare Fraud Scheme.'' See http://www.justice.gov/opa/pr/2013/March/13-crm-273.html . \\24...

76 FR 5061 - Special Conditions: TTF Aerospace, LLC, Modification to Boeing Model 767-300 Series Airplanes...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

..., will have a novel or unusual design features associated with the pilot lower lobe crew rest module (CRM...) for installation of a lower lobe pilot crew rest module (CRM) in Boeing Model 767-300 series airplanes. The CRM will be a one-piece, self-contained unit for installation in the forward portion of the aft...

Cockpit resource management skills enhance combat mission performance in a B-52 simulator

NASA Technical Reports Server (NTRS)

Povenmire, H. Kingsley; Rockway, Marty R.; Bunecke, Joseph L.; Patton, Mark W.

1989-01-01

A cockpit resource management (CRM) program for mission-ready B-52 aircrew is developed. The relationship between CRM performance and combat mission performance is studied. The performances of six crew members flying a simulated high workload mission in a B-52 weapon system trainer are evaluated. The data reveal that CRM performance enhances tactical maneuvers and bombing accuracy.

AFMC Customer Satisfaction Study at the Air Logistics Centers

DTIC Science & Technology

2008-03-01

research was guided by a previous Graduate Research Project (GRP) effort, which sought to determine how customer relationship management ( CRM ...and effectively. To accomplish this, AFMC is implementing Customer Relationship Management ( CRM ) as one of its initiatives. Problem Statement...for improvement. More than fifty-one percent of the participants were not aware that Customer Relationship Management ( CRM ) was a transformation

Customer relationship management in the contract pharmaceutical industry: an exploratory study for measuring success.

PubMed

Kros, John F; Nadler, Scott; Molis, Justin

2007-01-01

Managing customer relationships is a very important issue in business-to-business markets. This research investigates the growing number of available resources defining Customer Relationship Management (CRM) efforts, and how they are being applied within the Contract Pharmaceutical Manufacturing industry. Exploratory study results using face-to-face and telephone questionnaires based on four criteria for rating a company's CRM efforts are presented. Data was collected from large Contract Pharmaceutical Manufacturing companies in the US market. The results and conclusions are discussed relating how the Contract Pharmaceutical Manufacturing industry is implementing CRM including some potential steps to take when considering a CRM initiative.

Evaluation on the stability of Hg in ABS disk CRM during measurements by wavelength dispersive X-ray fluorescence spectrometry.

PubMed

Ohata, Masaki; Kidokoro, Toshihiro; Hioki, Akiharu

2012-01-01

The stability of Hg in an acrylonitrile-butadiene-styrene disk certified reference material (ABS disk CRM, NMIJ CRM 8116-a) during measurements by wavelength dispersion X-ray fluorescence (WD-XRF) analysis was evaluated in this study. The XRF intensities of Hg (L(α)) and Pb (L(α)) as well as the XRF intensity ratios of Hg (L(α))/Pb (L(α)) observed under different X-ray tube current conditions as well as their irradiation time were examined to evaluate the stability of Hg in the ABS disk CRM. The observed XRF intensities and the XRF intensity ratios for up to 32 h of measurements under 80 mA of X-ray tube current condition were constant, even though the surface of the ABS disk CRM was charred by the X-ray irradiation with high current for a long time. Moreover, the measurements on Hg and Pb in the charred disks by an energy dispersive XRF (ED-XRF) spectrometer showed constant XRF intensity ratios of Hg (L(α))/Pb (L(α)). From these results, Hg in the ABS disk CRM was evaluated to be sufficiently stable for XRF analysis.

Selection of the initial design for the two-stage continual reassessment method.

PubMed

Jia, Xiaoyu; Ivanova, Anastasia; Lee, Shing M

2017-01-01

In the two-stage continual reassessment method (CRM), model-based dose escalation is preceded by a pre-specified escalating sequence starting from the lowest dose level. This is appealing to clinicians because it allows a sufficient number of patients to be assigned to each of the lower dose levels before escalating to higher dose levels. While a theoretical framework to build the two-stage CRM has been proposed, the selection of the initial dose-escalating sequence, generally referred to as the initial design, remains arbitrary, either by specifying cohorts of three patients or by trial and error through extensive simulations. Motivated by a currently ongoing oncology dose-finding study for which clinicians explicitly stated their desire to assign at least one patient to each of the lower dose levels, we proposed a systematic approach for selecting the initial design for the two-stage CRM. The initial design obtained using the proposed algorithm yields better operating characteristics compared to using a cohort of three initial design with a calibrated CRM. The proposed algorithm simplifies the selection of initial design for the two-stage CRM. Moreover, initial designs to be used as reference for planning a two-stage CRM are provided.

Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.

PubMed

Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko

2016-08-31

Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (p<0.0001). Furthermore, the "short-term seroprotection rate" (anti-PRP antibody titer ⩾0.15μg/mL) before booster vaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. Registered on ClinicalTrials.gov: NCT01379846. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Combined resection of the nasal planum and premaxilla in three dogs.

PubMed

Kirpensteijn, J; Withrow, S J; Straw, R C

1994-01-01

Surgical techniques for removal of tumors that affect the nasal planum or the premaxilla have been described. For extensively invasive malignancies, these techniques may be inadequate if used alone to achieve wide surgical margins. An operative technique that combines resection of the nasal planum and premaxilla has been developed for extensive malignant tumors of the nasal planum or premaxilla. This technique was used in three dogs and resulted in an acceptable cosmetic appearance and good function and tumor control. Complications after surgery included minor bleeding and partial dehiscence of the suture lines in two dogs and stenosis of the nasal orifice in one dog.

Effect of skin barrier disruption on immune responses to topically applied cross-reacting material, CRM(197), of diphtheria toxin.

PubMed

Godefroy, S; Peyre, M; Garcia, N; Muller, S; Sesardic, D; Partidos, C D

2005-08-01

The high accessibility of the skin and the presence of immunocompetent cells in the epidermis makes this surface an attractive route for needle-free administration of vaccines. However, the lining of the skin by the stratum corneum is a major obstacle to vaccine delivery. In this study we examined the effect of skin barrier disruption on the immune responses to the cross-reacting material CRM(197), a nontoxic mutant of diphtheria toxin (DTx) that is considered as a vaccine candidate. Application of CRM(197), together with cholera toxin (CT), onto the tape-stripped skin of mice elicited antibody responses that had anti-DTx neutralizing activity. Vaccine delivery onto mildly ablated skin or intact skin did not elicit any detectable anti-CRM(197) antibodies. Mice immunized with CRM(197) alone onto the tape-stripped skin mounted a vigorous antigen-specific proliferative response. In contrast, the induction of cellular immunity after CRM(197) deposition onto mildly ablated or intact skin was adjuvant dependent. Furthermore, epidermal cells were activated and underwent apoptosis that was more pronounced when the stratum corneum was removed by tape stripping. Overall, these findings highlight the potential for transcutaneous delivery of CRM(197) and establish a correlation between the degree of barrier disruption and levels of antigen-specific immune responses. Moreover, these results provide the first evidence that the development of a transcutaneous immunization strategy for diphtheria, based on simple and practical methods to disrupt the skin barrier, is feasible.

The application of CRM to military operations

NASA Technical Reports Server (NTRS)

Cavanagh, Dale E.; Williams, Kenneth R.

1987-01-01

The detailed content of the CRM training component of the C-5 Aircrew Training System (ATS) was left to the discretion of the contractor. As a part of determining what the content should be, United Airlines Services Corporation has made an effort to understand how the needs of MAC crews compare with those of civilian airline crews. There are distinct similarities between the crew roles in the cockpits of civilian airliners and military air transports. Many of the attitudes and behaviors exhibited by civil and military crew members are comparable, hence much of the training in the field referred to as Cockpit Resource Management (CRM) is equally appropriate to civil or military aircrews. At the same time, there are significant differences which require assessment to determine if modifications to what might be termed generic CRM are necessary. The investigation enabled the definition and specification of CRM training which is believed to address the needs of the C-5 operational community. The study has concentrated largely on military airlift, but the training objectives and course content of the CRM training are readily adaptable to a wider range of military cockpits than are found in strategic airlift. For instance, CRM training focusing on communication, leadership, situational awareness, and crew coordination is just as appropriate, with some modification, to the pilots manning a flight to Tactical Airlift Command A-7's as it is to the pilots, flight engineers, and loadmasters crewing a C-5.

Classification for animal vocal fold surgery: resection margins impact histological outcomes of vocal fold injury.

PubMed

Imaizumi, Mitsuyoshi; Thibeault, Susan L; Leydon, Ciara

2014-11-01

Extent of vocal fold injury impacts the nature and timing of wound healing and voice outcomes. However, depth and extent of the lesion created to study wound healing in animal models vary across studies, likely contributing to different outcomes. Our goal was to create a surgery classification system to enable comparison of postoperative outcomes across animal vocal fold wound-healing studies. Prospective, controlled animal study. Rats underwent one of three types of unilateral vocal fold surgeries classified by depth and length of resection. The surgeries were: for subepithelial injury, resection of epithelium and superficial layer of the lamina propria at the midmembranous portion of the vocal fold; for transmucosal injury, resection of epithelium and lamina propria; and for transmuscular injury, resection of epithelium, lamina propria, and superficial portion of the vocalis muscle. Wound healing was evaluated histologically at various time points up to 35 days postinjury. Complete healing occurred by 14 days postsurgery for subepithelial injury, and by day 35 for transmucosal injury. Injury remained present at day 35 for transmuscular injury. Timing and completeness of healing varied by extent and depth of resection. Scarless healing occurred rapidly following subepithelial injury, whereas scarring was observed at 5 weeks after transmuscular injury. The proposed classification system may facilitate comparison of surgical outcomes across vocal fold wound-healing studies. N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Confocal Microscopy for the Histological Fluorescence Pattern of a Recurrent Atypical Meningioma: Case Report

PubMed Central

Whitson, Wesley J.; Valdes, Pablo A.; Harris, Brent T.; Paulsen, Keith D.; Roberts, David W.

2013-01-01

Background and Importance Fluorescence-guided resection with 5-aminolevulinic acid (5-ALA), which has shown promising results in the resection of malignant gliomas, has been used for meningioma resection in an attempt to more clearly delineate the tumor margin. However, no article has investigated the fluorescence pattern of meningiomas on a histological level. Understanding the microscopic pattern of fluorescence could help assess the precision and utility of using 5-ALA for these tumors. We present the case of a recurrent atypical meningioma operated on with 5-ALA fluorescence-guided resection for delineation of tumor tissue from surrounding uninvolved dura. Clinical Presentation A 53-year-old woman presented with recurrent atypical meningioma of the falx. Prior treatment included surgical resection 6 years earlier with subsequent fractionated radiation therapy and radiosurgery for tumor progression. The patient was given 5-ALA 20 mg/kg body weight dissolved in 100 mL water 3 hours before induction of anesthesia. Intraoperative fluorescence was coregistered with preoperative imaging. Neuropathological analysis of the resected falx with confocal microscopy enabled correlation of fluorescence with the extent of tumor on a histological level. Conclusion Fluorescence guidance allowed clear intraoperative delineation of tumor tissue from adjacent, uninvolved dura. On a microscopic level, there was a very close correlation of fluorescence with tumor, but some tumor cells did not fluoresce. PMID:21389893

Outcome of Laparoscopic Versus Open Resection for Transverse Colon Cancer.

PubMed

Zeng, Wei-Gen; Liu, Meng-Jia; Zhou, Zhi-Xiang; Hou, Hui-Rong; Liang, Jian-Wei; Wang, Zheng; Zhang, Xing-Mao; Hu, Jun-Jie

2015-10-01

Laparoscopic resection for transverse colon cancer remains controversial. The aim of this study is to investigate the short- and long-term outcomes of laparoscopic surgery for transverse colon cancer. A total of 278 patients with transverse colon cancer from a single institution were included. All patients underwent curative surgery, 156 patients underwent laparoscopic resection (LR), and 122 patients underwent open resection (OR). The short- and long-term results were compared between two groups. Baseline demographic and clinical characteristics were comparable between two groups. Conversions were required in eight (5.1 %) patients. LR group was associated with significantly longer median operating time (180 vs. 140 min; P < 0.001). Median estimated blood loss was significantly less in LR group (90 vs. 100 ml; P = 0.001). Time to first flatus and oral intake was significantly earlier in LR group. Perioperative mortality and morbidity rate were not significantly different between two groups. Tumor size, number of lymph nodes harvested, length of proximal, and distal resection margin were comparable between two groups. Postoperative hospital stay was significantly shorter in LR group (9 vs. 10d; P < 0.001). Five-year disease-free survival and overall survival rate were similar between two groups. Laparoscopic resection for transverse colon cancer is associated with better short-term outcomes and equivalent long-term oncologic outcomes.

Complete segmental resection of the spine, including the spinal cord, for telangiectatic osteosarcoma: a report of 2 cases.

PubMed

Murakami, Hideki; Tomita, Katsuro; Kawahara, Norio; Oda, Makoto; Yahata, Tetsutaro; Yamaguchi, Takehiko

2006-02-15

Two case reports of telangiectatic osteosarcoma treated with complete segmental resection of the spine, including the spinal cord. To report the en bloc tumor excision, including the spinal cord, for telangiectatic osteosarcoma, and discuss the indication of cord transection and influence after cutting the spinal cord. To our knowledge, there are no previous reports describing telangiectatic osteosarcoma of the spine and the subsequent en bloc excision of the spine, including the spinal cord. The clinical and radiographic presentations of 2 cases with telangiectatic osteosarcoma are presented. Because these 2 cases already had complete paralysis for at least 1 month, it was suspected that there was no possibility of recovering spinal cord function. Complete segmental spinal resection (total en bloc spondylectomy) was performed. At that level, the spinal cord was also cut and resected. En bloc excision of the tumor with a wide margin was achieved in both cases. In the resected specimen, the nerve cells in the spinal cord had lapsed into degenerative necrosis. The pathologic findings showed that there was no hope for recovery of spinal cord function. En bloc spinal resection, including the spinal cord, is an operation allowed when there is no hope for recovery of spinal cord function. This surgery should be accepted as an option in spine tumor surgeries.

Resection of a cholangiocarcinoma via laparoscopic hepatopancreato- duodenectomy: A case report

PubMed Central

Zhang, Miao-Zun; Xu, Xiao-Wu; Mou, Yi-Ping; Yan, Jia-Fei; Zhu, Yi-Ping; Zhang, Ren-Chao; Zhou, Yu-Cheng; Chen, Ke; Jin, Wei-Wei; Matro, Erik; Ajoodhea, Harsha

2014-01-01

Some laterally advanced cholangiocarcinomas behave as ductal spread or local invasion, and hepatopancreatoduodenectomy (HPD) may be performed for R0 resection. To date, there have been no reports of laparoscopic HPD (LHPD) in the English literature. We report the first case of LHPD for the resection of a Bismuth IIIa cholangiocarcinoma invading the duodenum. The patient underwent laparoscopic pancreaticoduodenectomy and right hemihepatectomy. Child’s approach was used for the reconstruction. The patient recovered well with bile leakage from the 2nd postoperative day and was discharged on the 16th postoperative day with a drainage tube in place which was removed 2 wk after discharge. Postoperative pathology revealed a well-differentiated cholangiocarcinoma and the margin of liver parenchyma, pancreas and stomach was negative for metastases. The results suggest that LHPD is a feasible and safe procedure when performed in highly specialized centers and in suitable patients with cholangiocarcinoma. PMID:25493044

[Primary cancer of the liver].

PubMed

Orozco, H; Mercado, M A

1997-01-01

The epidemiologic and pathogenic aspects of primary hepatic malignancies are discussed. The role of viruses in the etiology of the disease is stressed. Imageology methods have a preponderant role for diagnosis and treatment options. Liver resection has a one years survival between 60 and 80% and a five years survival of 20 to 40%. A good surgical results is expected for tumors with no more than 5 cm in diameter, encapsulated and without vascular invasion non-cirrhotic livers, large tumors can also be removed. Surgical resection margin should be of 1 cm. For cirrhotic livers, a good liver function is needed (Child A-B) and no safe major resection can be done. History of bleeding portal hypertension has a negative role in the outcome. Liver transplantation should be limited to selected case, in which the tumors are small and asymptomatic (incidental). For larger tumors, long term results are not good with invariable recurrency of the tumor.

Prosthetic rehabilitation of a marginally resected mandibular arch with a metal reinforced telescopic overdenture.

PubMed

Rohit, Raghavan; Prathith, Uthappa; Regish, K M; Rupesh, P L; Basavaraj, Salagundi; Padmanabhan, T V

2014-09-01

Success of the prosthesis after mandibular resection is related directly to the amount of the remaining bone and soft tissue present. The prognosis for mandibulectomy patients becomes less favorable as the size of the resection increases. Prosthetic rehabilitation for such patients is a challenge for clinicians. Without preprosthetic reconstructive surgery, denture fabrication for mandibulectomy patients becomes extremely difficult. Telescopic dentures is a modality of treatment consisting of an inner or primary telescopic coping which is permanently cemented to an abutment and an outer or secondary telescopic coping which is attached to the prosthesis. These copings protect the abutment from dental caries and thermal irritations and also provide retention and stabilization of the secondary coping. The secondary coping engages the primary copings to form a telescopic unit and it provides retention and stability to the prosthesis. This clinical report aims at utilizing the remaining natural teeth for a mandibular overdenture with telescopic coping.