Impact of primary tumor resection in the management of metastatic well-differentiated neuroendocrine tumors of the small bowel and pancreas.

Patients with gastroenteropancreatic (GEP) neuroendocrine tumors (NET) often present with advanced disease. Primary tumor resection (PTR) in the setting of unresectable metastatic disease is controversial. Most studies evaluating the impact of PTR on overall survival (OS) have been performed using large population-based databases, with limited treatment related data. This study aims to determine whether PTR improves OS and progression-free survival (PFS) in patients with metastatic well-differentiated GEP-NET. This is a retrospective single-institution study of patients with metastatic well-differentiated GEP-NET between 1978 and 2021. The primary outcome was OS. The secondary outcome was PFS. Chi-squared tests and Cox regression were used to perform univariate and multivariate analyses (MVA). OS and PFS were estimated using the Kaplan-Meier method and log-rank test. Between 1978 and 2021, 505 patients presented with metastatic NET, 151 of whom had well-differentiated GEP-NET. PTR was performed in 31 PNET and 77 SBNET patients. PTR was associated with improved median OS for PNET (136 vs. 61 months, p = .003) and SBNET (not reached vs. 79 months, p<.001). On MVA, only higher grade (HR 3.70, 95%CI 1.49-9.17) and PTR (HR 0.21, 95%CI 0.08-0.53) influenced OS. PTR resulted in longer median PFS for patients with SBNET (46 vs. 28 months, p = .03) and a trend toward longer median PFS for patients with PNET (20 vs. 13 months, p = .07). In patients with metastatic well-differentiated GEP-NET, PTR is associated with improved OS and may be associated with improved PFS and should be considered in a multidisciplinary setting. Future prospective studies are needed to validate these findings.

Seek and ye shall find: The utility of perioperative VTE screening in high-risk oncologic patients undergoing abdominopelvic surgery.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the prevalence and risk factors associated with perioperative venous thromboembolism (VTE) in patients undergoing major oncologic surgery using an epidural catheter (EC) for postoperative analgesia with mechanical prophylaxis and without chemoprophylaxis. METHODS: Six hundred and twenty-six patients undergoing major oncologic surgery from 2009 to 2023 were evaluated. VTE was defined as deep vein thrombosis above the level of the knee. Lower extremity venous duplexes (LEVDs) were done preoperatively and postoperatively after the EC was removed. All patients received mechanical thromboprophylaxis, but not chemical prophylaxis, while the EC was in place. A generalized linear multivariable model was constructed to identify risk factors that predict pre and postoperative VTE. RESULTS: 29/626 patients (4.6%) were found to have preoperative VTE. 16/626 (2.6%) were found to have a postoperative VTE when their preoperative LEVD was negative. In comparison to patients without preoperative VTE, those with VTE were more likely to be male, anticoagulated, and have a history of coronary artery disease. Patients in the postoperative VTE group were older, male, anticoagulated, and had a history of VTE. On multivariable analysis, previous history of VTE was the risk factor most strongly associated with both pre and postoperative VTE. CONCLUSION: Oncologic patients undergoing elective abdominopelvic surgery with epidural analgesia should be screened in the perioperative setting with LEVD to identify VTE and possibly prevent PE.

Preoperative Frailty and Malnutrition in Surgical Oncology Patients Predicts Higher Postoperative Adverse Events and Worse Survival: Results of a Blinded, Prospective Trial.

BACKGROUND: Frailty, a multidimensional state leading to reduced physiologic reserve, is associated with worse postoperative outcomes. Despite the availability of various frailty tools, surgeons often make subjective assessments of patients' ability to tolerate surgery. The Risk Analysis Index (RAI) is a validated preoperative frailty assessment tool that has not been studied in cancer patients with plans for curative-intent surgery. METHODS: In this prospective, surgeon-blinded study, patients who had abdominal malignancy with plans for resection underwent preoperative frailty assessment with the RAI and nutrition assessment by measurement of albumin, prealbumin, and C-reactive protein (CRP). Postoperative outcomes and survival were assessed. RESULTS: The study included 220 patients, 158 (72%) of whom were considered frail (RAI ≥21). Frail patients were more likely to be readmitted within 30 and 90 days, (16% vs. 3% [P = 0.006] and 16% vs. 5% [P = 0.025], respectively). Patients with abnormal CRP, prealbumin, and albumin experienced higher rates of unplanned intensive care unit admission (CRP [27% vs. 8%; P < 0.001], albumin [30% vs. 10%; P < 0.001], prealbumin [29% vs. 9%; P < 0.001]) and increased postoperative mortality at 90 and 180 days. Survival was similar for frail and non-frail patients. In the multivariate analysis, frailty remained an independent risk factor for readmission (hazard ratio, 5.58; 95% confidence interval, 1.39-22.15; P = 0.015). In the post hoc analysis using the pre-cancer RAI score, the postoperative outcomes did not differ between the frail and non-frail patients. CONCLUSION: In conjunction with preoperative markers of nutrition, the RAI may be used to identify patients who may benefit from additional preoperative risk stratification and increased postoperative follow-up evaluation.

Association of Parental Status and Gender With Burden of Multidisciplinary Tumor Boards Among Oncology Physicians.

Importance: Tumor boards are integral to the care of patients with cancer. However, data investigating the burden of tumor boards on physicians are limited. Objective: To investigate what physician-related and tumor board-related factors are associated with higher tumor board burden among oncology physicians. Design, Setting, and Participants: Tumor board burden was assessed by a cross-sectional convenience survey posted on social media and by email to Cedars-Sinai Medical Center cancer physicians between March 3 and April 3, 2022. Tumor board start times were independently collected by email from 22 top cancer centers. Main Outcomes and Measures: Tumor board burden was measured on a 4-point scale (1, not at all burdensome; 2, slightly burdensome; 3, moderately burdensome; and 4, very burdensome). Univariable and multivariable probabilistic index (PI) models were performed. Results: Surveys were completed by 111 physicians (median age, 42 years [IQR, 36-50 years]; 58 women [52.3%]; 60 non-Hispanic White [54.1%]). On multivariable analysis, factors associated with higher probability of tumor board burden included radiology or pathology specialty (PI, 0.68; 95% CI, 0.54-0.79; P = .02), attending 3 or more hours per week of tumor boards (PI, 0.68; 95% CI, 0.58-0.76; P < .001), and having 2 or more children (PI, 0.65; 95% CI, 0.52-0.77; P = .03). Early or late tumor boards (before 8 am or at 5 pm or after) were considered very burdensome by 33 respondents (29.7%). Parents frequently reported a negative burden on childcare (43 of 77 [55.8%]) and family dynamics (49 of 77 [63.6%]). On multivariable analysis, a higher level of burden from early or late tumor boards was independently associated with identifying as a woman (PI, 0.69; 95% CI, 0.57-0.78; P = .003) and having children (PI, 0.75; 95% CI, 0.62-0.84; P < .001). Independent assessment of 358 tumor boards from 22 institutions revealed the most common start time was before 8 am (88 [24.6%]). Conclusions and Relevance: This survey study of tumor board burden suggests that identifying as a woman or parent was independently associated with a higher level of burden from early or late tumor boards. The burden of early or late tumor boards on childcare and family dynamics was commonly reported by parents. Having 2 or more children, attending 3 or more hours per week of tumor boards, and radiology or pathology specialty were associated with a significantly higher tumor board burden overall. Future strategies should aim to decrease the disparate burden on parents and women.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: Effects of postoperative fluids beyond the first 24 h.

BACKGROUND AND OBJECTIVES: There are no guidelines for intravenous fluid (IVF) administration after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study assessed rates of post-CRS/HIPEC morbidity according to perioperative IVF administration. METHODS: All patients undergoing CRS/HIPEC March 2007 to June 2018 were reviewed, recording clinicopathologic, operative, and postoperative variables. Patients were divided by peritoneal cancer index (PCI), comparing IVF volumes and types administered intraoperatively and during the first 72 h postoperatively. Optimal IVF rate cutoffs calculated using area under the receiver operating characteristic curves and Youden's index determined associations with complications. RESULTS: Overall, 185 patients underwent CRS/HIPEC, and 81 (51%) had low PCI (<10) and 77 (49%) had high PCI (≥10). In low-PCI patients, high IVF rates on postoperative days (POD) #0-2 were associated with higher overall complications: POD#0 (46% vs. 89%, p = 0.001), POD#1 (40% vs. 86%, p < 0.05), and POD#2 (42% vs. 72%, p < 0.05). High IVF rates were associated with respiratory distress (7% vs. 26%, p = 0.02) on POD#0, ileus (14% vs. 47%, p = 0.007) and intensive care unit stay (11% vs. 33%, p = 0.022) on POD#1, and ICU stay (8% vs. 33%, p = 0.003) on POD#2. CONCLUSIONS: For low PCI patients undergoing CRS/HIPEC, higher IVF rates were associated with postoperative complications. Post-CRS/HIPEC, IVF rates should be limited to prevent morbidity.

Contemporary Cancer Program Practice Profile Report Compliance Rates for Gastric Cancer: A National Cancer Database Analysis.

BACKGROUND: The Commission on Cancer (CoC) established quality measures to be reported in National Cancer Database (NCDB) Quality Reporting Tools. Compliance is provided to accredited cancer programs as Cancer Program Practice Profile Reports (CP3R). At the time of this study, the quality metric for gastric cancer (GC) was removal and pathologic examination of 15 regional lymph nodes for resected GC (G15RLN). OBJECTIVE: This study evaluates national trends in quality metric compliance for GC based on CoC CP3R. METHODS: The National Cancer Database (NCDB) was queried from 2004-2017 to identify patients with stage I-III GC who met criteria for inclusion. National trends in compliance were compared. Overall survival (OS) was compared stage for stage. RESULTS: Overall, 42 997 patients with GC qualified. In 2017, 64.5% of patients met compliance with G15RLN compared to 31.4% in 2004. When comparing academic and non-academic institutions, compliance was met 67.0% vs 60.0% of the time in 2017 (P < .01) and 36% vs 30.6% of the time in 2004 (P < .01). On multivariate logistic regression, patients receiving care at academic institutions (OR 1.5, 95% CI 1.4-1.5) and who underwent surgery at institutions in the >75th percentile for case volume (OR 1.5, 95% CI 1.4-1.6) had higher odds of compliance. When stratified by stage, median OS was better across all stages when compliance was met. CONCLUSION: Compliance rates with GC quality measures have improved over time. Compliance with the G15RLN metric is associated with improved OS, stage for stage. Continued efforts to improve compliance rates across all institutions are critical.

Postoperative Respiratory Failure Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy is Associated with Volume of Intraoperative Crystalloid Administration and Worse Survival.

BACKGROUND: Postoperative respiratory failure (PRF) is associated with increased morbidity after surgery. This retrospective study explores preoperative and perioperative risk factors associated with PRF in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and the resultant impact on survival. METHODS: We identified all patients who underwent CRS/HIPEC at our institution between 2007 and 2017. PRF was defined as mechanical ventilation for more than 48 h after surgery or reintubation not related to an additional procedure within the first 30 days postoperatively. The relationship between clinicopathologic variables and PRF was examined using Kaplan-Meier log-rank survival analysis and multivariable Cox regression models with 90-day, 1-year and 5-year overall survival (OS). RESULTS: Overall, 314 patients underwent CRS/HIPEC, of whom 24 patients (7.6%) developed PRF. On univariable analysis, chronic obstructive pulmonary disease (COPD) was the only preoperative risk factor associated with PRF (p = 0.049). Of the intraoperative risk factors, diaphragmatic resection (p = 0.008), Peritoneal Cancer Index (PCI) > 20 (p < 0.001), and volume of intraoperative crystalloid (p < 0.001) were all associated with PRF. On multivariable Cox regression, only intraoperative crystalloid was significantly associated with PRF (p < 0.001), with a volume above 5.3 L (area under the curve [AUC] 0.77) having a high predictive accuracy for PRF. Five-year OS was significantly decreased in patients with PRF (30.2% vs. 52.6%, hazard ratio 2.6, 95% confidence interval 1.5-4.4; p < 0.001). CONCLUSIONS: Liberal intraoperative crystalloid volume resuscitation is a potential independent, modifiable intraoperative risk factor for PRF following CRS/HIPEC that may contribute to decreased long-term OS.

Hypophosphatemia Is Associated With Postoperative Morbidity After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy: A Retrospective Study.

INTRODUCTION: Hypophosphatemia following surgery is associated with a higher rate of postoperative complications; however, the significance of postoperative hypophosphatemia after cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) is unknown. METHODS: A prospectively maintained database was queried for all patients who underwent CRS/HIPEC for any histology at the Mount Sinai Health System. The perioperative serum phosphate levels, postoperative complications, and comorbidities were compared between patients with or without major complications. RESULTS: From 2007 to 2018, 327 patients underwent CRS/HIPEC. Most of the patients had low phosphate levels on postoperative day (POD) 2, reaching a median nadir of 2.3 mg/dL on POD 3. Patients with major complications had significantly lower levels of serum phosphate on POD 5-7 compared with patients without complications, with median serum phosphate 2.2 mg/dL (IQR 1.9-2.4) versus 2.7 mg/dL, (IQR 2.3-3), P < 0.01. Hypophosphatemia on POD 5-7 was also more frequent in patients who developed an anastomotic leak, with median serum phosphate 2.2 mg/dL (IQR 1.9-2.6) versus 2.8 mg/dL (IQR 2.2-3.2), P = 0.001. On multivariate analysis, the number of organs resected at surgery, diaphragm resection, postoperative intensive care unit stay, and serum phosphate level <2.4 mg/dL on POD 5-7 were independently associated with a major complication after CRS/HIPEC. CONCLUSIONS: Following CRS/HIPEC, POD 5-7 hypophosphatemia is associated with severe postoperative complications and anastomotic leak.

The Role of Surgeon-Performed Office and Preincision Ultrasounds in Localization of Parathyroid Adenomas in Primary Hyperparathyroidism.

OBJECTIVE: We studied the use of surgeon-performed office ultrasound (OU) and preincision ultrasound (PIU) in preoperatively localizing parathyroid adenomas in primary hyperparathyroidism (PHPT). METHODS: A retrospective chart review was performed for patients with PHPT who underwent parathyroidectomy between 2013 and 2015. The results of OU and PIU were recorded and compared with the final surgical pathology. RESULTS: Of 348 patients with PHPT, 285 (81.9%) had single-lesion disease, 49 (14.1%) had double-lesion disease, and 14 (4.0%) had multigland disease with 3 or more lesions. For single-lesion disease, the overall sensitivity and specificity of OU to correctly lateralize the lesion were 64.2% and 91.2%, while those of PIU were 89.4% and 93.6%, respectively. The sensitivity and specificity of PIU were comparable to those of 4-dimensional computed tomography (87.1% and 90.7%, respectively) and 99mTc-sestamibi scintigraphy (70.4% and 95.9%, respectively). While the majority of PIU cases were preceded by other imaging studies, the accuracy in localizing lesions was not largely affected by the presence of prior computed tomography and/or 99mTc-sestamibi scintigraphy, as opposed to ultrasounds only. For detecting the presence of multigland disease, the sensitivity and specificity of OU were 26% and 92.2%, while those of PIU were 64.3% and 94.7%, respectively. CONCLUSION: Surgeon-performed OU and PIU are valuable tools in preoperatively localizing the parathyroid adenoma in single-lesion disease, while their utility may be limited for double-lesion or multigland disease. PIU in particular yields high accuracy in detecting parathyroid lesions in combination with other imaging modalities.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is associated with improved perioperative outcomes: a single-center early experience propensity-matched analysis.

INTRODUCTION: The role of laparoscopy in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is not well established. Herein, we describe our early experience of laparoscopic CRS/HIPEC in patients with low-volume peritoneal disease compared to patients who underwent open CRS/HIPEC during the same time period. METHODS: Using a prospectively maintained database, patients who underwent laparoscopic CRS/HIPEC were compared to a control cohort of patients who underwent open CRS/HIPEC, matched for peritoneal carcinomatosis index (PCI), completeness of cytoreduction, and tumor histology. RESULTS: Between 2008 and 2017, 16 patients underwent laparoscopic CRS/HIPEC and were compared to a matched control cohort of 32 patients who underwent open CRS/HIPEC. Clinical and demographic data were similar between the groups. PCI, number of resected organs, and optimal cytoreduction rates were comparable. Patients who underwent laparoscopic experienced a lower estimated blood loss, (median, [IQR 1-3]); 150 mL, [50-300] vs. 100 mL, [50-125], p = 0.04, shorter length of stay (median [IQR 1-3]; 4 days [3-6] vs. 6 days [5-8], p < 0.01, and a lower 30-day complication rate (6.3% vs. 56.3%, p < 0.01). There was no difference in progression-free survival (p = 0.577) and overall survival (p = 0.472) between the groups. CONCLUSIONS: This preliminary study demonstrates that laparoscopic CRS/HIPEC is feasible and safe for curative treatment in selected patients with low tumor volume. Minimally invasive CRS/HIPEC is associated with fewer postoperative complications and shorter length of stay. There was no difference in long-term oncological outcomes between the groups.

Lymphocyte-to-monocyte ratio predicts survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Aim: Lymphocyte-to-monocyte ratio (LMR) predicts overall survival (OS) in patients with colorectal cancer. We explored LMR in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Materials & methods: We identified all patients undergoing CRS/HIPEC for colorectal or appendiceal adenocarcinoma at our institution. We analyzed LMR's relationship with clinicopathologic variables with Kaplan-Meier log-rank survival analyses and multivariable Cox regression models with 5-year OS. Results: Two hundred and sixteen patients underwent CRS/HIPEC. Five-year OS for low LMR (≤3.71) was 35.2 versus 60.4% for elevated LMR (hazard ratio [HR]: 2.0; 95% CI: 1.1-3.5; p = 0.02). On multivariable Cox-regression, elevated LMR was significantly associated with OS (p ≤ 0.05). Conclusion: LMR is an independent predictor of OS in patients undergoing CRS/HIPEC for colorectal and appendiceal adenocarcinoma.

Hepatitis C-positive Black patients develop hepatocellular carcinoma at earlier stages of liver disease and present with a more aggressive phenotype.

BACKGROUND: In the United States, mortality after a diagnosis of hepatocellular carcinoma (HCC) is higher in patients who are Black than in patients of other racial groups. The objective of this study was to clarify factors contributing to this disparity by analyzing liver and tumor characteristics in patients with HCC who have a history of hepatitis C virus (HCV) infection. METHODS: Records of patients with HCV and HCC at the authors' institution from 2003 to 2018 were retrospectively reviewed. Race and ethnicity were self-identified. Imaging, laboratory, and pathologic features were compared between Black and non-Black cohorts. RESULTS: Among 1195 individuals with HCC, 390 identified as Black. At the time of HCC diagnosis, Black patients had better liver function, as measured by Child-Pugh score, Model of End-Stage Liver Disease score, histology of nontumor tissue, and fibrosis-4 (FIB-4) score (all P < .05). FIB-4 scores were <3.25 in 31% of Black patients. In addition, Black patients had less early stage HCC (20.2% vs 32.3%; P < .05), larger tumors (median [interquartile range]: 3.5 cm [2.2-6.2 cm] vs 3.1 cm [2.1-5.1 cm]; P < .01), more multiple tumors (median, [interquartile range]: 1 tumor [1-3 tumors] vs 1 tumor [1-2 tumors]; P = .03), more poorly differentiated tumors (30.3% vs 20.5%; P < .05), and more microvascular invasion (67.2% vs 56.5%; P < .05). CONCLUSIONS: Black patients with HCV exposure develop HCC at earlier stages of liver disease than members of other racial groups. Nearly one-third would not qualify for HCC screening using the common FIB-4 cirrhosis threshold. Practice guidelines that stress HCC surveillance for cirrhotic patients with HCV may need to be revised to be more inclusive for Black patients. In addition, tumors in Black patients carry worse prognostic features, and molecular studies are needed to characterize their biologic properties.

The significance of anatomic tumor location in gallbladder cancer.

BACKGROUND AND OBJECTIVES: Current management guidelines recognize the impact of hepatic versus peritoneal sided gallbladder cancers (GBC) on survival. However, no data exist regarding the significance of anatomic tumor location within the gallbladder. METHODS: We retrospectively analyzed all GBC that underwent surgical resection with curative intent in our health system from 2007 to 2017. We evaluated the effect of anatomic pathologic tumor location (fundus/body, neck, and multifocal) on clinicopathologic, perioperative, and oncologic outcomes. RESULTS: About 97 patients met criteria; 63% fundus/body, 22% multifocal, and 15% neck. Compared with fundus/body, neck tumors more frequently presented with preoperative jaundice (53% vs. 13%, p < .001), were smaller (20 mm vs. 30 mm, p = .068) and had significantly more biliary tree invasion (33% vs. 13%, p = .030) on histopathology. Although tumor characteristics (pTNM stage, liver invasion, lymphovascular invasion, prognostic nutritional index, and grade) were similar, neck tumors had significantly higher rates of R0 resection (53% vs. 11%, p < .001). Rates of adjuvant therapy were similar. Median PFS was similar between cohorts (p = .356). However, median overall survival (OS) was significantly shorter in neck (21 months) than fundus/body tumors (NR > 109 months), p = .015. CONCLUSIONS: Neck tumors were rare, small and more likely to result in jaundice secondary to biliary tree invasion. Despite higher R0 resection rates, these tumors had significantly worse OS.

The importance of primary tumor origin in gastrointestinal malignancies undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Appendiceal and colorectal cancers with peritoneal carcinomatosis (PC) can derive benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, its role in gastric and small bowel malignancies remains undefined. METHODS: We retrospectively analyzed 251 gastrointestinal adenocarcinomas with PC which underwent CRS/HIPEC at our institution from 2007 to 2017. We compared outcomes of gastric, small bowel, appendiceal, and colorectal cohorts. RESULTS: Thirty-one gastric, 8 small bowel, 91 appendiceal, and 121 colorectal cohorts were included. More gastric cancers (90%) received neoadjuvant chemotherapy than any other cohort, p = 0.002. Although colorectal had the lowest peritoneal cancer index (PCI) (9) and appendiceal the highest (16), all cohorts underwent similar rates of organ resection and complete cytoreduction. Length of stay (p = 0.005) and major perioperative morbidity (Clavien III/IV, p = 0.011) were significantly higher in gastric and small bowel. Median overall survival (OS, p < 0.001) was significantly shorter in gastric (13 months) and small bowel (9 months) than in appendiceal (33 months) and colorectal (42 months) cohorts. On multivariate analysis, complete cytoreduction and PCI score were significant predictors of OS, p < 0.05. CONCLUSIONS: Primary tumor origin significantly affects outcomes after CRS/HIPEC for gastrointestinal malignancies. Though there was a survival benefit in appendiceal and colorectal, gastric and small bowel survival was comparable to systemic chemotherapy.

Adeno-squamous and squamous cell carcinoma of the gallbladder: The importance of histology in surgical management.

BACKGROUND: Although gallbladder adenocarcinoma (AC) is potentially curable with resection, outcomes of squamous histologies are poorly described. METHODS: We retrospectively analyzed all gallbladder cancers which underwent resection-for-cure in our health system from 2007 to 2017. We compared outcomes of AC to adeno-squamous (ASC)/squamous (SC) histologies. RESULTS: 91 patients met criteria; 76 AC, 15 ASC/SC. Compared to AC, ASC/SC tumors were larger (58 vs. 28 mm), with more frequent liver invasion (73% vs. 37%), pN+ (60% vs. 32%), higher stage (III/IV 73% vs. 52%), and displayed more LVI (60% vs. 36%), p < 0.05. For stage III/IV disease, provided R0 was achieved, survival was durable and similar for ASC/SC and AC (OS median 28mo ASC/SC vs. 25mo AC, p = 0.132; PFS median 21mo ASC/SC vs. 13mo AC, p = 0.206). Pure SC had considerably poorer median OS (<5mo) than ASC (23mo) and AC (28mo). DISCUSSION: Squamous variants of gallbladder cancer confer aggressive and advanced disease and often require more radical resections to achieve R0. Durable survival is possible in ASC provided R0 is achieved. Pure SC has dismal survival even with R0 resection.

Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy indicated in hepatobiliary malignancies?

BACKGROUND: Hepatopancreaticobiliary malignancies with peritoneal carcinomatosis exhibit poor survival with current therapies: hepatocellular carcinoma 11 months with sorafenib, and pancreaticobiliary 9-14 months with systemic chemotherapy. However, limited data exist on the utility of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. METHODS: We retrospectively reviewed our institutional hepatopancreaticobiliary malignancies with peritoneal carcinomatosis which underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy from 2007 to 2017 and analyzed perioperative and oncologic outcomes. RESULTS: Seventeen patients were included: 9 hepatocellular carcinoma, 8 pancreaticobiliary (4 cholangiocarcinoma, 3 gallbladder, 1 pancreatic). Peritoneal cancer index, number of organs resected, completeness of cytoreduction, and 30-day morbidity were equivalent. Hepatocellular carcinoma received significantly less neoadjuvant therapy (11%, p = 0.008), though adjuvant therapy rates were similar. At a median follow-up of 15 months, progression-free survival was similar amongst all cohorts. However, overall survival was longer in hepatocellular carcinoma (42 months vs. cholangiocarcinoma 19 months, gallbladder 8 months, pancreatic 15 months, p = 0.206) with 59% 3-year overall survival (vs. 0% cholangiocarcinoma, 0% gallbladder, 0% pancreatic). CONCLUSIONS: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy may offer a survival benefit in select hepatocellular carcinoma patients with peritoneal carcinomatosis, though has dubious utility in pancreaticobiliary malignancies.

Peritoneal Cancers and Hyperthermic Intraperitoneal Chemotherapy.

Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy is an aggressive, potentially curative approach used to treat locoregional disease associated with primary and secondary malignancies of the peritoneum. It involves resection of all macroscopic disease larger than 2.5 mm, followed by instillation of hyperthermic chemotherapy directly into the peritoneum for higher drug exposure to microscopic disease. In select patients with primary peritoneal mesothelioma, pseudomyxoma peritonei, colorectal adenocarcinoma, appendiceal adenocarcinoma, or ovarian cancer, with no extra-abdominal metastasis and limited involvement of the peritoneum, the procedure can be performed to increase overall survival.

Diaphragmatic Peritoneal Stripping Versus Full-Thickness Resection in CRS/HIPEC: Is There a Difference?

BACKGROUND: Pleural recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rare and poorly delineated. Specifically, data are limited on the effect that diaphragmatic peritoneal stripping versus full-thickness resection has on the nature of ipsilateral pleural recurrence and postoperative morbidity. METHODS: Patients with peritoneal carcinomatosis who underwent CRS/HIPEC were included from a prospectively maintained database. The patients were divided into three cohorts based on surgical management of the diaphragm as follows: diaphragm-stripping (DS) cohort, full-thickness resection (FTR) cohort, and no diaphragm manipulation (ND) cohort. Postoperative morbidity and incidence of ipsilateral pleural recurrence were evaluated. All diaphragmatic defects were closed before abdominal chemoperfusion. RESULTS: The inclusion criteria were met by 409 CRS/HIPEC procedures: 66 in DS, 122 in FTR, and 238 in ND. Ipsilateral pleural recurrence rates did not differ significantly between the three cohorts (DS 6%, FTR 3%, ND 3%; p = 0.470). Postoperative respiratory complications and overall morbidity were significantly greater for the patients who underwent diaphragmatic disruption (stripping and/or resection) than for the patients who did not (p ≤ 0.0001), but the two groups did not differ in terms of 30-day mortality. However, comparison of FTR with DS showed no impact on major morbidity or pleural recurrence. CONCLUSION: Although patients undergoing surgical manipulation of the diaphragm during CRS/HIPEC experienced significantly greater morbidity, diaphragmatic stripping did not differ from full-thickness resection in terms of grades 3 and 4 complications or incidence of ipsilateral pleural recurrences. When deemed necessary to achieve complete cytoreduction, full-thickness diaphragmatic resection should be undertaken. In addition, the data support the observation that definitive repair of the diaphragmatic defect before abdominal chemoperfusion does not adversely influence ipsilateral pleural recurrence.

Acute and specific modulation of presynaptic aromatization in the vertebrate brain.

Estrogens affect a diversity of peripheral and central physiological endpoints. Traditionally, estrogens were thought to be peripherally derived transcription regulators (i.e. slow acting). More recently, we have learned that estrogens are also synthesized in neuronal cell bodies and synaptic terminals and have potent membrane effects, which modulate brain function. However, the mechanisms that control local steroid concentrations in a temporal and spatial resolution compatible with their acute actions are poorly understood. Here, using differential centrifugation followed by enzymatic assay, we provide evidence that estrogen synthesis within synaptosomes can be modulated more dramatically by phosphorylating conditions, relative to microsomes. This is the first demonstration of a rapid mechanism that may alter steroid concentrations within the synapse and may represent a potential mechanism for the acute control of neurophysiology and behavior.