Factors Impacting Academic Productivity and Satisfaction of Surgeon-scientists: A Nationwide Survey.

OBJECTIVE: To identify factors related to research success for academic surgeons. SUMMARY BACKGROUND DATA: Many recognize mounting barriers to scientific success for academic surgeons, but little is known about factors that predict success for individual surgeons. METHODS: A phase 1 survey was emailed to department chairpersons at highly funded US departments of surgery. Participating chairpersons distributed a phase 2 survey to their faculty surgeons. Training- and faculty-stage exposures and demographic data were collected and compared with participant-reported measures of research productivity. Five primary measures of productivity were assessed including number of grants applied for, grants funded, papers published, first/senior author papers published, and satisfaction in research. RESULTS: Twenty chairpersons and 464 faculty surgeons completed the survey, and 444 faculty responses were included in the final analysis. Having a research-focused degree was significantly associated with more grants applied for (PhD, incidence rate ratio (IRR)=6.93; masters, IRR=4.34) and funded (PhD, IRR=4.74; masters, IRR=4.01) compared to surgeons with only clinical degrees (all P<0.01). Having a formal research mentor was significantly associated with more grants applied for (IRR=1.57, P=0.03) and higher satisfaction in research (IRR=2.22, P<0.01). Contractually protected research time was significantly associated with more grants applied for (IRR=3.73), grants funded (IRR=2.14), papers published (IRR=2.12), first/senior authors published (IRR=1.72), and research satisfaction (Odds ratio=2.15) (all P<0.01). The primary surgeon-identified barrier to research productivity was lack of protection from clinical burden. CONCLUSIONS: Surgeons pursuing research-focused careers should consider the benefits of attaining a research-focused degree, negotiating for contractually protected research time, and obtaining formal research mentorship.

Genetic Clustering of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Patients of Colorectal Origin: KRAS and Not TP53 Cluster Alterations are Associated with Poor Outcomes.

BACKGROUND: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined. OBJECTIVE: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population. METHODS: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics. RESULTS: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05). CONCLUSIONS: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.

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.

Racial disparities of gastric cancer in the USA: an overview of epidemiology, global screening guidelines, and targeted screening in a heterogeneous population.

Gastric cancer is the fifth most common cancer diagnosis and fourth leading cause of cancer-related death globally. The incidence of gastric cancer in the USA shows significant racial and ethnic disparities with gastric cancer incidence in Korean Americans being over five times higher than in non-Hispanic whites. Since gastric cancer is not common in the USA, there are no current screening guidelines. In countries with higher incidences of gastric cancer, screening guidelines have been implemented for early detection and intervention and this has been associated with a reduction in mortality. Immigrants from high incidence countries develop gastric cancer at lower rates once outside of their country of origin, but continue to be at higher risk for developing gastric cancer. This risk does seem to decrease with subsequent generations. With increasing availability of endoscopy, initiating gastric cancer screening guidelines for high-risk groups can have the potential to improve survival by diagnosing and treating gastric cancer at an earlier stage. This article aims to provide context to gastric cancer epidemiology globally, review risk factors for developing gastric cancer, highlight racial and ethnic disparities in gastric cancer burden in the USA, examine current guidelines that exist in high incidence countries, and suggest future studies examining the efficacy of additional screening in high-risk populations to reduce gastric cancer mortality and disparate burden on ethnic minorities in the USA.

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.

Association of Systemic Chemotherapy Approaches With Outcomes in Appendiceal Peritoneal Metastases.

INTRODUCTION: Many patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal adenocarcinoma peritoneal metastases (APM) undergo preoperative systemic chemotherapy. The primary aim of this study is to evaluate differences in oncologic outcomes among two popular chemotherapy approaches in patients with APM undergoing CRS-HIPEC. METHODS: We performed a multicenter retrospective review of patients who underwent CRS-HIPEC for APM due to high or intermediate grade disease between 2013 and 2019. Patients in the total neoadjuvant therapy group (TNT) received 12 cycles of preoperative chemotherapy. Patients in the "sandwich" chemotherapy group (SAND) received six cycles of preoperative chemotherapy with a maximum of six cycles of postoperative chemotherapy. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS) defined as months from date of first treatment or surgery, respectively. RESULTS: A total of 39 patients were included in this analysis, with 25 (64%) patients in the TNT group and 14 (36%) patients in the SAND group. Patients in the TNT group had a median OS of 62 mo, while median OS in the SAND group was 45 mo (P = 0.01). In addition, patients in the TNT group had significantly longer RFS compared to the SAND group (35 versus 12 mo, P = 0.03). In a multivariable analysis, TNT approach was independently associated with improved OS and RFS. CONCLUSIONS: In this multicenter retrospective analysis, a TNT approach was associated with improved overall and recurrence-free survival compared to a sandwiched chemotherapy approach in patients undergoing CRS-HIPEC for high or intermediate grade APM.

A total neoadjuvant chemotherapy approach is associated with improved recurrence-free survival in patients with colorectal peritoneal metastases undergoing cytoreductive surgery and HIPEC.

BACKGROUND: The primary aim of this study is to evaluate the oncologic outcomes of two popular systemic chemotherapy approaches in patients with colorectal peritoneal metastases (CPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: We performed a dual-center retrospective review of consecutive patients who underwent CRS-HIPEC for CPM due to high or intermediate-grade colorectal cancer. Patients in the total neoadjuvant therapy (TNT) group received 6 months of preoperative chemotherapy. Patients in the "sandwich" (SAND) chemotherapy group received 3 months of preoperative chemotherapy with a maximum of 3 months of postoperative chemotherapy. RESULTS: A total of 34 (43%) patients were included in the TNT group and 45 (57%) patients in the SAND group. The median overall survival (OS) in the TNT and SAND groups were 77 and 61 months, respectively (p = 0.8). Patients in the TNT group had significantly longer recurrence-free survival (RFS) than the SAND group (29 vs. 12 months, p = 0.02). In a multivariable analysis, the TNT approach was independently associated with improved RFS. CONCLUSION: In this retrospective study, a TNT approach was associated with improved RFS, but not OS when compared with a SAND approach. Further prospective studies are needed to examine these systemic chemotherapeutic approaches in patients with CPM undergoing CRS-HIPEC.

Synovial sarcoma with intra-abdominal metastasis causing hemoperitoneum: a case-report.

Synovial sarcoma is a rare soft tissue sarcoma which frequently involves the upper or lower extremities. Soft tissue sarcomas including synovial sarcoma have a propensity to metastasize to the lungs, and there are very few reports of metastatic lesions in other locations.Here, we report a case of a 49-year-old patient who underwent neoadjuvant chemoradiation for an upper extremity synovial sarcoma and presented approximately 4 years later with abdominal pain and hemoperitoneum and was ultimately found to have metastatic synovial sarcoma involving the greater curvature of the stomach and surrounding peri-gastric soft tissue. We describe the multidisciplinary management of this complex patient presentation and propose that expanded surveillance imaging beyond that of the local tumor resection bed and the chest may be beneficial especially in tumors with high-risk features.

Impact of Insurance Status on Oncologic and Perioperative Outcomes After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: A growing body of research has shown that underinsured patients are at increased risk of worse health outcomes compared with insured patients. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is largely performed at highly specialized cancer centers and may pose challenges for the underinsured. This study investigates surgical outcomes following CRS-HIPEC for insured and underinsured patients with peritoneal carcinomatosis. METHODS: We performed a retrospective cohort study of 125 patients undergoing CRS-HIPEC between 2013 and 2019. Patients were categorized into two groups. The insured group was comprised of patients with private insurance at the time of CRS-HIPEC or who obtained it during the follow-up period. The underinsured group consisted of patients with Medicaid, or self-pay. Perioperative and oncologic outcomes were compared between the two groups. RESULTS: A total of 102 (82.3%) patients were insured, and 22 (17.7%) patients were underinsured. There were no significant differences in age, medical morbidities, primary tumor characteristics, peritoneal carcinomatosis index, or completion of cytoreduction score between the two groups. The median overall survival (OS) for insured patients was 64.8 months and was 52.9 months for underinsured patients (p = 0.01). Additionally, insured patients had a significantly longer follow-up time. Underinsurance status also was associated with increased hospital and intensive care unit length of stay, and higher rate of Clavien-Dindo classification III-IV complications. CONCLUSIONS: In this retrospective study conducted at a large, urban, specialized cancer center, private insurance status was associated with increased overall survival and longer follow-up period. Furthermore, underinsurance status was associated with increased perioperative morbidity.

Gallbladder Cancer: A Single-Institution 10-Year Experience-Analysis of Adenocarcinoma Subtypes and Tumors Arising from Intracholecystic Papillary Neoplasms.

BACKGROUND: Gallbladder cancer accounts for 1.2% of global cancer diagnoses. Literature on biliary-type adenocarcinoma (BTA), and specifically carcinoma arising from intracholecystic papillary-tubular neoplasms (ICPNs), is limited. This study describes a retrospective, single-institution experience with gallbladder cancer, focusing on histological subtypes and prognosis. METHODS: A retrospective review was performed of patients who underwent cholecystectomy for a malignant neoplasm of the gallbladder between 2007 and 2017. Demographic, clinicopathologic, and operative variables, as well as survival outcomes, were analyzed. RESULTS: From a total of 145 patients, BTAs were most common (93, 64%). Compared with non-BTAs, BTAs were diagnosed at a lower American Joint Committee on Cancer stage (p = 0.045) and demonstrated longer median recurrence-free survival (38 vs. 16 months, p = 0.014; median follow-up 36 months). Tumors arising from ICPNs (18, 12%) were more commonly associated with BTA (14 cases). Compared with BTAs not associated with ICPNs (29 patients), associated cases demonstrated lower pathologic stage (p = 0.006) and lower rates of liver and perineural invasion (0% vs. 49% and 14% vs. 48%, respectively; p < 0.05). Cumulative 5-year survival probability was higher for patients with gallbladder neoplasm of any subtype associated with ICPNs compared with those that were not associated with ICPNs (54% vs. 41%, p = 0.019; median follow-up 23 months). This difference was also significant when comparing BTAs associated with ICPNs and non-associated cases (63% vs. 52%, p = 0.005). CONCLUSIONS: This study demonstrated unique pathological and prognostic features of BTAs and of carcinomas arising from ICPNs. Histopathological variance may implicate prognosis and may be used to better guide clinical decision making in the treatment of these patients.

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.

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.

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 role of molecular biomarkers in outcomes and patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases of colorectal origin.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is effective in select patients with peritoneal metastases of colorectal (CRC) origin. The impact of different biomarkers in predicting recurrence after CRS/HIPEC is unclear. METHODS: Retrospective review of patients who underwent CRS/HIPEC for PC of CRC origin from 03/2007-08/2017. Molecular profile of the primary tumor was obtained from pathology reports, whenever available. RESULTS: Overall, 100 patients underwent CRS/HIPEC for peritoneal metastases of CRC origin. Most patients presented high grade tumor histology (G2/G3, n = 97, 97%), and a majority showed mucinous features (n = 61, 61%). At a median follow-up of 18 months, median DFS for the overall population was 13 months (95% CI 9.6, 16.4). Data reporting at least one mutational analysis was available in 64 patients. Microsatellite stability was detected in 42/50 (84%) patients, mKRAS in 25/51 (49%), and mBRAF in 5/35 (14.3%). On Kaplan-Meier analysis, BRAF was the only mutation associated with poor DFS (16 months, CI 95% 11.7-43.3 vs. 7 months, CI 95% 2.1-11.9, p = .008). On multivariate analysis, mBRAF independently predicted earlier recurrence (p = .032). CONCLUSIONS: In this analysis, mBRAF was independently associated with earlier recurrence in patients undergoing CRS/HIPEC for CRC, leading to dismal median DFS (7 months). Strict patient selection is advisable in these patients.

Improved Survival with Experience: A 10-Year Learning Curve in Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an aggressive locoregional treatment for peritoneal carcinomatosis (PC). Studies demonstrate improved perioperative and oncologic outcomes at high-volume centers. METHODS: This study retrospectively analyzed all patients with PC from various malignancies who underwent attempted CRS/HIPEC at the authors' institution from 2007 to 2017. Clinicopathologic, perioperative, and oncologic outcomes of early (2007-2012) and late (2012-2017) experience were compared, and multivariate analyses for factors predictive of perioperative and oncologic outcomes were performed. RESULTS: The study enrolled 388 patients (157 early and 231 late). The late experience contained more appendiceal low-grade mucinous neoplasms (LGMNs; 21% vs 9%) and had a lower Peritoneal Cancer Index (PCI; 10 vs 16). Moreover, achieving a similar rate of CC-0/1 required fewer organ resections, involved shorter operations (298 vs 347 min), and had lower estimated blood loss (EBL) (400 vs 200 ml) (p < 0.05). More procedures were aborted (20% vs 3%; p < 0.01). The late experience had fewer ICU admissions (13% vs. 55%) and a lower perioperative mortality rate (0% vs 3%) (p < 0.05). In the multivariate analyses, PCI and number of organ resections were independent predictors of multiple perioperative outcomes [EBL, operating room time, intensive care unit (ICU) admission, ICU length of stay (LOS), overall LOS]. Survival was significantly longer in the late cohort (median overall survival: NR vs 31 months; progression-free survival: 22 vs 11 months; p < 0.01), even after control for tumor histology. CONCLUSIONS: At the authors' high-volume center, with increased surgeon and institutional experience over time, perioperative and oncologic outcomes have improved significantly for patients undergoing CRS/HIPEC for PC.

The Safety of Iterative Cytoreductive Surgery and HIPEC for Peritoneal Carcinomatosis: A High Volume Center Prospectively Maintained Database Analysis.

INTRODUCTION: Offering iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for recurrence of peritoneal carcinomatosis (PC) poses a surgical dilemma. Safety of this repeated operation in the short and long term has not been largely investigated. METHODS: Patients with PC who underwent 377 CRS/HIPEC procedures between 2007 and 2018 at our institution were included from a prospectively maintained database. Outcomes for patients who had singular CRS/HIPEC were compared with those for patients who had repeated CRS/HIPEC. RESULTS: Overall, there were 325 singular and 52 iterative CRS/HIPEC procedures performed during this time period. Age, sex, and ASA class were comparable between cohorts (p = NS). Optimal cytoreduction, mean operative time, mean length of hospital stay, 90-day major morbidity, and 90-day mortality were also similar. At a median follow-up of 24 months, there was no significant difference in recurrence rate (%, 60 vs 63, p = 0.76), disease-free survival (mean months, 19 vs 15, p = 0.30), and overall survival (mean months, 32 vs 27, p = 0.69). The iterative CRS/HIPEC group had significantly higher rates of major late complications than the singular CRS/HIPEC group (%, 18 vs 40, p < 0.01). CONCLUSION: Repeated CRS/HIPEC for PC has similar perioperative morbidity and mortality, as well as long-term oncological benefits, when compared with singular CRS/HIPEC. However, more than twice as many patients undergoing iterative CRS/HIPEC suffered from major late complications.

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.

Surveillance of Low-Grade Appendiceal Mucinous Neoplasms With Peritoneal Metastases After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Are 5 Years Enough? A Multisite Experience.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMNs) are tumors that often present with widespread mucin in the peritoneal cavity (pseudomyxoma peritonei [PMP]). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective treatment, but no published recommendations exist regarding surveillance. METHODS: Data from prospective databases of patients who underwent CRS-HIPEC from 2001 to 2017 at two high-volume institutions were retrospectively analyzed. Patients who underwent complete CRS-HIPEC for PMP secondary to LAMN were included in the analysis. Pathologic examination confirmed the diagnosis of LAMN. Cases of mucinous adenocarcinomas and neuroendocrine tumors (goblet cell carcinoids) were excluded. RESULTS: The study enrolled 156 patients. The median peritoneal cancer index (PCI) was 18 (interquartile range IQR1-3, 12-23), and 125 patients (80.1%) had a CC0 cytoreduction. According to American Joint Committee on Cancer (AJCC) grading, 152 patients (97.4%) presented with acellular mucin or G1 implants, 2 patients (1.3%) presented with G2 disease, and 2 patients (1.3%) presented with G3 disease. During the follow-up period (median, 45 months; IQR1-3 23-76 months), 23 patients (14.7%) experienced recurrence. All the recurrences were peritoneal and occurred within 5 years. The 1-, 3-, and 5-year disease-free survival (DFS) rates were respectively 95.5%, 83.4%, and 78.3%. Univariate Cox regression analysis showed that higher PCI scores (p < 0.001), a CC1 cytoreduction (p = 0.005), and higher preoperative levels of carcinoembryonic antigen (CEA) (p = 0.012) and CA-125 (p = 0.032) correlated with a shorter DFS. Only higher PCI scores independently predicted earlier recurrences (p < 0.001). CONCLUSION: Most patients had recurrence within 3 years after CRS-HIPEC, and none after 5 years. High PCI was the only independently significant variable. The study findings support intensive surveillance (every 3-6 months) with tumor markers and imaging methods during the first 3 years, and annual surveillance thereafter, with follow-up assessment after 5 years yielding limited benefit.

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.