Determination of “borderline resectable” pancreatic cancer – A global assessment of 30 shades of grey

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis. Accurate preoperative assessment using computed tomography (CT) to determine resectability is crucial in ensuring patients are offered the most appropriate therapeutic strategy. Despite the use of classification guidelines, any interobserver variability between reviewing surgeons and radiologists may confound decisions influencing patient treatment pathways. Methods: In this multicentre observational study, an international group of 96 clinicians (42 hepatopancreatobiliary surgeons and 54 radiologists) were surveyed and asked to report 30 pancreatic CT scans of pancreatic cancer deemed borderline at respective multidisciplinary meetings (MDM). The degree of interobserver agreement in resectability among radiologists and surgeons was assessed and subgroup regression analysis was performed. Results: Interobserver variability between reviewers was high with no unanimous agreement. Overall interobserver agreement was fair with a kappa value of 0.32 with a higher rate of agreement among radiologists over surgeons. Conclusion: Interobserver variability among radiologists and surgeons globally is high, calling into question the consistency of clinical decision making for patients with PDAC and suggesting that central review may be required for studies of neoadjuvant or adjuvant approaches in future as well as ongoing quality control initiatives, even amongst experts in the field

Pancreatic endometriosis: a systematic review

BACKGROUND: Extrapelvic manifestations of endometriosis can be identified in nearly every part of the female body, and the true prevalence of extrapelvic locations is unknown. Pancreatic endometriosis may manifest in several ways, ranging from emergency presentations to asymptomatic cysts. METHOD: A systematic PubMed and Scopus search was conducted. RESULTS: Eighteen patients from 17 case reports were included. The patients' mean age was 39.3 (range: 21-72) years. An emergency presentation was noted in 8 of the 18 (44.4%) patients. Menstrual irregularity was present in 3 (16.7%) patients, while in 3 (16.7%) cases there was simultaneous presence of endometriosis elsewhere. The most frequent symptoms at presentation of pancreatic endometrial cysts were epigastric pain, acute left upper quadrant pain, back pain, nausea/vomiting/diarrhea, which occurred in 12 (66.7%), 11 (61.1%), 4 (22.2%), and 6 (33.3%) patients, respectively. Only one case presented as an asymptomatic pancreatic cyst. The maximum diameter of the endometrial cysts ranged from 1-16 cm. In the majority of cases, surgical treatment was offered (16/18, 88.9%). Recurrence of pancreatic endometrial cyst occurred in one case only, following needle aspiration of the endometrial cyst. No fatality was reported. CONCLUSIONS: Review of the available published literature suggests that pancreatic endometriosis is a rare condition that should be included in the differential diagnosis of pancreatic masses. Further clinical and experimental studies are necessary to investigate the pathogenesis of extrapelvic and pancreatic endometriosis.UnknownThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

The Feasibility of Cardiophrenic Lymphnode Assessment and Removal in Patients Requiring Diaphragmatic Resection During Interval Debulking Surgery for Ovarian Cancer

Background: Several studies have demonstrated the feasibility and role of bulky cardiophrenic lymph nodes (CPLNs) resection during primary debulking surgery (PDS) for stage IV ovarian cancer (OC). However, no studies, to date, investigated the accuracy and feasibility of CPLNs assessment and removal during interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT). Material and Methods: A retrospective analysis of consecutive stage IV OC patients who underwent NACT followed by IDS with CPLNs assessment and/or resection from July 2017 to June 2018. Bulky CPLNs were considered for excision when a full-thickness diaphragmatic resection was required in order to achieve complete tumour resection. Results: A total of 21 ovarian cancer stage IV patients treated with NACT followed by IDS were identified. Seven (33.3%) patients underwent CPLNs resection due to bulky appearance of the CPLNs at the intraoperative palpation. The final histological examination of the CPLNs reported metastatic disease in four (57%) of seven patients. Complete cytoreduction without residual disease was achieved in five cases (71.4%) while in two case (28.6%) optimal cytoreduction was performed. Intra-operative surgical complications occurred in one patient. One patient had a major postoperative complication (Clavien-Dindo 3). Two cases of postoperative cardiac arrhythmia were observed. Conclusions: CPLNs intraoperative assessment is less accurate during IDS compared to previous PDS studies. CPLNs removal during IDS after NACT for stage IV OC could be safely performed to achieve a complete resection

The Feasibility of Cardiophrenic Lymphnode Assessment and Removal in Patients Requiring Diaphragmatic Resection During Interval Debulking Surgery for Ovarian Cancer

Background: Several studies have demonstrated the feasibility and role of bulky cardiophrenic lymph nodes (CPLNs) resection during primary debulking surgery (PDS) for stage IV ovarian cancer (OC). However, no studies, to date, investigated the accuracy and feasibility of CPLNs assessment and removal during interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT). Material and Methods: A retrospective analysis of consecutive stage IV OC patients who underwent NACT followed by IDS with CPLNs assessment and/or resection from July 2017 to June 2018. Bulky CPLNs were considered for excision when a full-thickness diaphragmatic resection was required in order to achieve complete tumour resection. Results: A total of 21 ovarian cancer stage IV patients treated with NACT followed by IDS were identified. Seven (33.3%) patients underwent CPLNs resection due to bulky appearance of the CPLNs at the intraoperative palpation. The final histological examination of the CPLNs reported metastatic disease in four (57%) of seven patients. Complete cytoreduction without residual disease was achieved in five cases (71.4%) while in two case (28.6%) optimal cytoreduction was performed. Intra-operative surgical complications occurred in one patient. One patient had a major postoperative complication (Clavien-Dindo 3). Two cases of postoperative cardiac arrhythmia were observed. Conclusions: CPLNs intraoperative assessment is less accurate during IDS compared to previous PDS studies. CPLNs removal during IDS after NACT for stage IV OC could be safely performed to achieve a complete resection

Interval Debulking Surgery for Advanced Ovarian Cancer in Elderly Patients ( 6570 y): Does the Age Matter?

Background: Elderly ovarian cancer (OC) patients are more likely to be managed suboptimally, with worse clinical outcomes as a result. Strategies to decrease morbidity are lacking. Methodology: Consecutive patients with advanced stage OC (IIIC-IV) who were managed in our center between January 2016 and July 2018 were retrospectively analyzed. All patients underwent neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) according to our institution protocol. We divided patients into two groups: Group 1 (age 65 70 years) and Group 2 (age < 70 years). The primary outcome of the study was assessment of peri-operative morbidity amongst two groups. Results: A total of 153 patients were referred during the study period. 114 patients underwent IDS after NACT (74.5%), 46 in Group 1 and 68 in Group 2. Elderly patients were more likely to receive more than three cycles of NACT prior to IDS compared to younger patients (39% vs. 19%, p = 0.03). Elderly patients were more frequently subjected to Cardiopulmonary Exercise Testing (CPET) as pre-operative assessment (63% vs. 27%, p = 0.002). Optimal/complete resection was achieved in all patients in Group 1 (100%) and in 97% of patients in Group 2. With the exception of higher postoperative cardiac arrhythmias in Group 1 (11% vs. 1%, p = 0.04), no significant differences in 30-day morbidity were observed. No 90-day death in both groups was registered. Conclusion: Older age should not preclude clinicians from offering ultra-radical resection to patients with advanced OC after NACT. In our series, elderly patients received the same treatment with similar outcomes to the younger group. Clinicians should be encouraged to use CPET for patients\u2019 selection following NACT

Angiogenic and Antiangiogenic VEGFA Splice Variants in Colorectal Cancer: Prospective Retrospective Cohort Study in Patients Treated With Irinotecan-Based Chemotherapy and Bevacizumab

We investigated the predictive and prognostic significance of tumoral messenger RNA levels of vascular endothelial growth factor A (VEGFS) splice variants in metastatic colorectal cancer (mCRC) patients treated with bevacizumab. VEGFA145b had negative predictive significance predominantly in those patients with right-sided primary tumors. All VEGFAxxxb variants were negative prognosticators for patients with right-sided mCRC, whereas VEGFA165b was of favorable prognostic significance in patients with left-sided tumors. © 2019 Elsevier Inc. Background: Alternative splicing of vascular endothelial growth factor A (VEGFA) results in VEGFAxxxb antiangiogenic isoforms that fail to activate angiogenesis. Bevacizumab, widely used in patients with metastatic colorectal cancer (CRC), binds both VEGFA and VEGFAxxxb isoforms. Patients and Methods: Formalin-fixed, paraffin-embedded primary tumors from metastatic CRC patients treated with first-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) + bevacizumab (n = 285) or FOLFIRI only (n = 75) were collected. The relative expression of VEGFA121a, 121b, 145a, 145b, 165a, and 165b was assessed with custom TaqMan-MGB assays and quantitative PCR. Results: At a median follow-up of 101.5 months, left-sided primary CRC was a favorable prognosticator (median survival, 29.2 vs. 18.2 months; P = .015). Positive high VEGFA145b was an unfavorable factor for progression-free survival (PFS; hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.13-2.44; P = .009) in patients who received FOLFIRI + bevacizumab, without prognostic significance in FOLFIRI-only patients (HR = 0.70; 95% CI, 0.34-1.44; P = .33). The adverse effect on PFS of 145b was more pronounced in patients with right-sided colon cancer (HR = 2.62; 95% CI, 1.35-5.12; P = .005), especially in those who received bevacizumab (HR = 2.85; 95% CI, 1.31-6.21; P = .008). In patients with right-sided colon primary tumors, isoform 121b correlated with inferior PFS (HR = 1.73; 95% CI, 0.94-3.18; P = .076) and overall survival (OS; HR = 2.0; 95% CI, 1.08-3.72; P = .028). In patients with left-sided primary tumors, positive high 165b correlated with superior PFS (HR = 0.76; 95% CI, 0.59-0.99; P = .044) and OS (HR = 0.68; 95% CI, 0.52-0.90; P = .006). At multivariate analysis, right-sided primary tumor was associated with inferior PFS (HR = 1.28; 95% CI, 1.00-1.64), while 145b consistently retained predictive significance for lack of benefit in PFS with bevacizumab (HR = 1.71; 95% CI, 1.16-2.53). Multivariate analysis for OS showed that VEGFA165b expression was favorable in patients with left-sided but unfavorable in patients with right-sided primary tumors (Pinteraction < .001). Conclusion: The antiangiogenic isoform VEGFA145b messenger RNA may predict resistance to bevacizumab. Differences in biological relevance and prognostic significance of various VEGFA isoforms were found for right- versus left-sided primary tumors. © 2019 Elsevier Inc

Restoring capability of friction pendulum seismic isolation systems

The restoring (or re-centring) capability is an important feature of any isolation system and a fundamental requirement of current standards and guideline specifications for the design of seismically isolated structures. In this paper, the restoring capability of spherical sliding isolation systems, often referred to as friction pendulum systems (FPSs), is investigated through an extensive parametric study involving thousands of non-linear response history analyses of SDOF systems. The dynamic behavior of the isolation system is described with the visco-plastic model of Constantinou et al. (J Struct Eng 116(2):455–474, 1990), considering the variability of the friction coefficient with sliding velocity and contact pressure. Numerical analyses have been carried out using a set of approximately three hundred natural seismic ground motions recorded during different earthquakes and differing in seismic intensity, frequency content characteristics, magnitude, epicentral distance and soil characteristics. Regression analysis has been performed to derive the dependency of the residual displacement from the parameters governing the dynamic response of FPS. The influence of near-fault earthquakes and the accumulation of residual displacements due to real sequences of seismic ground motions have been also investigated. Finally, the restoring compliance criteria proposed in this study are compared to the lateral restoring force requirements of current seismic codes. Based on the results of this study, useful recommendations for a (more) rational design of FPSs are outlined

Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study

Background: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. Methods: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan–Meier method and Cox regression analyses. Results: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. Conclusion: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype