Elevated Maximum Core Body Temperature During Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) is Associated with Increased Postoperative Complications.

BACKGROUND: Hyperthermia enhances the cytotoxicity of chemotherapeutic agents used during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC). However, this may result in an elevated core body temperature (CBT), with unintended effects on surgical morbidity. This study evaluates the relationship of maximum CBT during CRS/HIPEC on postoperative outcomes. METHODS: A retrospective review of patients undergoing CRS/HIPEC from January 2011 to July 2017 was performed. Outcomes were stratified according to maximum CBT reached during HIPEC. Primary study endpoints were 30-day morbidity and 30-day complication severity. RESULTS: Overall, 135 consecutive CRS/HIPEC cases were reviewed; 36 (27%) had a maximum CBT ≥ 39.5 °C during the 90-min HIPEC. CBT ≥ 39.5 °C was associated with an increase in 30-day postoperative complications (58% vs. 34%, p = 0.01) and severe Clavien-Dindo grade III or higher complications (22% vs. 11%, p = 0.04). On multivariate analysis, the adjusted odds ratio of having any complication was 3.77 (95% confidence interval [CI] 1.56-9.14) and a Clavien-Dindo grade III or higher complication was 3.46 (95% CI 1.10-10.95) when maximum CBT reached 39.5 °C. Flow rates ≥ 2.35 L/min were associated with lower average CBT (p = 0.05) and improved peritoneal heating (p = 0.02). CONCLUSION: Maximum CBT ≥ 39.5 °C is associated with an increased risk of postoperative morbidity. Higher flow rates are associated with improved intraperitoneal heating, lower CBT, and may contribute to optimizing the therapeutic benefit of HIPEC.

CRS/HIPEC with Major Organ Resection in Peritoneal Mesothelioma Does not Impact Major Complications or Overall Survival: A Retrospective Cohort Study of the US HIPEC Collaborative.

INTRODUCTION: CRS/HIPEC is thought to confer a survival advantage for patients with malignant peritoneal mesothelioma (MPM). However, the impact of nonperitoneal organ resection is not clearly defined. We evaluated the impact of major organ resection (MOR) on postoperative outcomes and overall survival (OS). PATIENTS AND METHODS: The US HIPEC collaborative database (2000-2017) was reviewed for MPM patients who underwent CRS/HIPEC. MOR was defined as total or partial resection of diaphragm, stomach, spleen, pancreas, small bowel, colon, rectum, kidney, ureter, bladder, and/or uterus. MOR was categorized as 0, 1, or 2+ organs. RESULTS: A total of 174 patients were identified. Median PCI was 16 (3-39). The distribution of patients with MOR-0, MOR-1, and MOR-2+ was 94, 45, and 35 patients, respectively. MOR-1 and MOR-2+ groups had a higher frequency of any complication compared with MOR-0 (57.8%, 74.3%, and 48.9%, respectively, p = 0.035), but Clavien 3/4 complications were similar. Median length of stay was slightly higher in the MOR-1 and MOR-2+ groups (10 and 11 days) compared with the MOR-0 cohort (9 days, p = 0.005). Incomplete cytoreduction, ASA class 4, and male gender were associated with increased mortality on unadjusted analysis; however, their impact on OS was attenuated on multivariable analysis. MOR was not associated with OS based on these data (MOR-1: HR 1.67, 95% CI 0.59-4.74; MOR-2+ : HR 0.77, 95% CI 0.22-2.69). CONCLUSIONS: MOR was not associated with an increase in major complications or worse OS in patients undergoing CRS/HIPEC for MPM and should be considered, if necessary, to achieve complete cytoreduction for MPM patients.

Repeat Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Is Not Associated with Prohibitive Complications: Results of a Multiinstitutional Retrospective Study.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is offered to select patients with peritoneal metastases. In instances of recurrence/progression, a repeat CRS/HIPEC may be considered. The perioperative morbidity and the potential oncologic benefits are not well described. PATIENTS AND METHODS: We performed a retrospective analysis of a multiinstitutional database to assess the perioperative outcomes following repeat CRS/HIPEC (repeat). Kaplan-Meier and Cox estimates were used to assess survival. RESULTS: In the entire cohort, 2157 patients were analyzed, with 158 (7.3%) in the repeat cohort. The rate of complete cytoreduction was 89.8% versus 83.0% in initial versus repeat groups. The overall incidence of major complications was similar (26.3% vs. 30.7%); however, reoperation was more common in the repeat group. Perioperative outcomes such as length of stay and nonhome discharge were not significantly different. For the entire cohort, 5-year overall survival (OS) was 56.0% in the initial group and 59.5% in the repeat group. In patients with only appendiceal cancer, we observed a 5-year OS of 64.0% in the initial group compared with 67.3% in the repeat cohort. For patients with appendiceal cancer who developed a recurrence/progression, median OS was 36 months in the no repeat operation group compared with 73 months for those that did. Multivariable regression demonstrated that completeness of cytoreduction and tumor grade were associated with OS, but repeat operation was not. CONCLUSIONS: Repeat CRS/HIPEC is not associated with prohibitive risk. Survival is possibly improved, and therefore, repeat operation should be considered in selected patients with recurrent or progressive disease.

Implications of Postoperative Complications for Survival After Cytoreductive Surgery and HIPEC: A Multi-Institutional Analysis of the US HIPEC Collaborative.

BACKGROUND: Postoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on the survival of patients with appendiceal or colorectal cancer after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is unknown. METHODS: The US HIPEC Collaborative (2000-2017) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. The analysis was stratified by noninvasive appendiceal neoplasm versus invasive appendiceal/colorectal adenocarcinoma. The POCs were grouped into infectious, cardiopulmonary, thromboembolic, and intestinal dysmotility. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS: Of the 1304 patients, 33% had noninvasive appendiceal neoplasm (n = 426), and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the noninvasive appendiceal cohort, POCs were identified in 55% of the patients (n = 233). The 3-year OS and RFS did not differ between the patients who experienced a complication and those who did not (OS, 94% vs 94%, p = 0.26; RFS, 68% vs 60%, p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased 3-year OS (59% vs 74%; p < 0.001) and RFS (32% vs 42%; p < 0.001). Infectious POCs were the most common (35%; n = 196). In Multivariable analysis accounting for gender, peritoneal cancer index (PCI), and incomplete resection (CCR1), infectious POCs in particular were associated with decreased OS compared with no complication (hazard ratio [HR] 2.08; p < 0.01) or other types of complications (HR, 1.6; p < 0.01). Similarly, infectious POCs were independently associated with worse RFS (HR 1.61; p < 0.01). CONCLUSION: Postoperative complications are associated with decreased OS and RFS after CRS/HIPEC for invasive histology, but not for an indolent disease such as noninvasive appendiceal neoplasm, and this association is largely driven by infectious complications. The exact mechanism is unknown, but may be immunologic. Efforts must target best practices and standardized prevention strategies to minimize infectious postoperative complications.

Optimal Surveillance Frequency After CRS/HIPEC for Appendiceal and Colorectal Neoplasms: A Multi-institutional Analysis of the US HIPEC Collaborative.

BACKGROUND: No guidelines exist for surveillance following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal and colorectal cancer. The primary objective was to define the optimal surveillance frequency after CRS/HIPEC. METHODS: The U.S. HIPEC Collaborative database (2000-2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC for appendiceal or colorectal cancer. Radiologic surveillance frequency was divided into two categories: low-frequency surveillance (LFS) at q6-12mos or high-frequency surveillance (HFS) at q2-4mos. Primary outcome was overall survival (OS). RESULTS: Among 975 patients, the median age was 55 year, 41% were male: 31% had non-invasive appendiceal (n = 301), 45% invasive appendiceal (n = 435), and 24% colorectal cancer (CRC; n = 239). With a median follow-up time of 25 mos, the median time to recurrence was 12 mos. Despite less surveillance, LFS patients had no decrease in median OS (non-invasive appendiceal: 106 vs. 65 mos, p < 0.01; invasive appendiceal: 120 vs. 73 mos, p = 0.02; colorectal cancer [CRC]: 35 vs. 30 mos, p = 0.8). LFS patients had lower median PCI scores compared with HFS (non-invasive appendiceal: 10 vs. 19; invasive appendiceal: 10 vs. 14; CRC: 8 vs. 11; all p < 0.01). However, on multivariable analysis, accounting for PCI score, LFS was still not associated with decreased OS for any histologic type (non-invasive appendiceal: hazard ratio [HR]: 0.28, p = 0.1; invasive appendiceal: HR: 0.73, p = 0.42; CRC: HR: 1.14, p = 0.59). When estimating annual incident cases of CRS/HIPEC at 375 for non-invasive appendiceal, 375 invasive appendiceal and 4410 colorectal, LFS compared with HFS for the initial two post-operative years would potentially save $13-19 M/year to the U.S. healthcare system. CONCLUSIONS: Low-frequency surveillance after CRS/HIPEC for appendiceal or colorectal cancer is not associated with decreased survival, and when considering decreased costs, may optimize resource utilization.

Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative.

BACKGROUND: For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3. METHODS: All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort). RESULTS: Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained. CONCLUSION: The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.

Predictors of Anastomotic Failure After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Does Technique Matter?

BACKGROUND: Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood. METHODS: Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula). RESULTS: Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p < 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p > 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p < 0.01), higher complication rate (90% vs 59%; p < 0.01), higher reoperation rate (41% vs 9%; p < 0.01), more 30-day readmissions (59% vs 22%; p < 0.01), greater 30-day mortality (9% vs 1%; p < 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p < 0.01). CONCLUSIONS: Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

Predictors of Non-home Discharge after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients. METHODS: Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD. RESULTS: The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P < 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P < 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P < 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P < 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P < 0.001). CONCLUSIONS: Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs.

The impact of HIPEC vs. EPIC for the treatment of mucinous appendiceal carcinoma: a study from the US HIPEC collaborative.

INTRODUCTION: Mucinous appendiceal carcinoma is a rare malignancy that commonly spreads to the peritoneum leading to peritoneal metastases. Complete cytoreduction with perioperative intraperitoneal chemotherapy (PIC) is the mainstay of treatment, administered as either hyperthermic intra peritoneal chemotherapy (HIPEC) or early post-operative intraperitoneal chemotherapy (EPIC). Our goal was to assess the perioperative and long term survival outcomes associated with these two PIC methods. MATERIALS AND METHODS: Patients with mucinous appendiceal carcinoma were identified in the US HIPEC Collaborative database from 12 academic institutions. Patient demographics, clinical characteristics, and survival outcomes were compared among patients who underwent HIPEC vs. EPIC with inverse probability weighting (IPW) used for adjustment. RESULTS: Among 921 patients with mucinous appendiceal carcinoma, 9% underwent EPIC while 91% underwent HIPEC. There was no difference in Grade III-V complications between the two groups (18.5% for HIPEC vs. 15.0% for EPIC, p=.43) though patients who underwent HIPEC had higher rates of readmissions (21.2% vs. 8.8%, p<.01). Additionally, PIC method was not an independent predictor for overall survival (OS) or recurrence-free survival (RFS) after adjustment on multivariable analysis. CONCLUSIONS: Among patients with mucinous appendiceal carcinoma, both EPIC and HIPEC appear to be associated with similar perioperative and long-term outcomes.

Restrictive Intraoperative Fluid Therapy is Associated with Decreased Morbidity and Length of Stay Following Hyperthermic Intraperitoneal Chemoperfusion.

BACKGROUND: Recent data have demonstrated multiple benefits of intra- and postoperative fluid restriction in major abdominal surgery; however, data regarding the outcomes of fluid restriction in cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) are limited. This study evaluates the safety and short-term clinical outcomes of restricted intraoperative fluid therapy in CRS/HIPEC. METHODS: This was a single-institution, retrospective review of all CRS/HIPEC procedures performed at the University of Massachusetts Medical School between January 2009 and July 2017. Recorded variables included demographics, intraoperative factors, 60-day postoperative complications, and length of stay (LOS). Outcomes based on the use of intraoperative permissive fluid therapy (PFT) versus restrictive fluid therapy (RFT) were compared. RESULTS: Overall, 169 CRS/HIPEC cases were performed during the study period; 84 were managed with PFT and 85 were managed with RFT. No significant differences were identified in patient demographics. There was a decrease in intraoperative administration of crystalloid (8.0 vs. 4.4 L, p < 0.01), colloid (900 vs. 300 mL, p < 0.01), and blood transfusion (0.26 vs. 0.04 units, p < 0.01) in the RFT cohort. LOS was reduced from 11.5 to 9.7 days (p < 0.01) and the incidence of any 60-day complication decreased from 45 to 28% (p = 0.02) in the RFT group. The overall 90-day mortality rate was 0.6% (n = 1). Adjusted logistic regression demonstrated the odds of having a Clavien-Dindo grade III or higher complication was 0.31 (95% confidence interval 0.10-0.95) with RFT. CONCLUSION: Intraoperative RFT with standard anesthesia monitoring devices can be safely used in CRS/HIPEC and is associated with a decreased LOS and decreased rate of postoperative complications.

Primary Tumor Sidedness is Predictive of Survival in Colon Cancer Patients Treated with Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy: A US HIPEC Collaborative Study.

INTRODUCTION: The clinical relevance of primary tumor sidedness is not fully understood in colon cancer patients with peritoneal metastasis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This was a retrospective cohort study of a multi-institutional database of patients with peritoneal surface malignancy at 12 participating high-volume academic centers from the US HIPEC Collaborative. RESULTS: Overall, 336 patients with colon primary tumors who underwent curative-intent CRS with or without HIPEC were identified; 179 (53.3%) patients had right-sided primary tumors and 157 (46.7%) had left-sided primary tumors. Patients with right-sided tumors were more likely to be older, male, have higher Peritoneal Cancer Index (PCI), and have a perforated primary tumor, but were less likely to have extraperitoneal disease. Patients with complete cytoreduction (CC-0/1) had a median disease-free survival (DFS) of 11.5 months (95% confidence interval [CI] 7.6-15.3) versus 13.1 months (95% CI 9.5-16.8) [p = 0.158] and median overall survival (OS) of 30 months (95% CI 23.5-36.6) versus 45.4 months (95% CI 35.9-54.8) [p = 0.028] for right- and left-sided tumors; respectively. Multivariate analysis revealed that right-sided primary tumor was an independent predictor of worse DFS (hazard ratio [HR] 1.75, 95% CI 1.19-2.56; p =0.004) and OS (HR 1.72, 95% CI 1.09-2.73; p = 0.020). CONCLUSION: Right-sided primary tumor was an independent predictor of worse DFS and OS. Relevant clinicopathologic criteria, such as tumor sidedness and PCI, should be considered in patient selection for CRS with or without HIPEC, and guide stratification for clinical trials.

A multi-institutional analysis of Textbook Outcomes among patients undergoing cytoreductive surgery for peritoneal surface malignancies.

BACKGROUND: While recent studies have introduced the composite measure of a textbook outcome (TO) for measuring postoperative outcomes, the incidence of a TO has not been characterized among patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies (PSM). STUDY DESIGN: All patients who underwent CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 1999 and 2017 from 12 institutions were included. A TO was defined as the absence of any of the following criteria: completeness of cytoreduction >1, reoperation within 90-days, readmission within 90-days, mortality within 90-days, any grade ≥2 complication, hospital stay >75th percentile, and non-home discharge. RESULTS: Among 1904 patients who underwent CRS, only 30.9% achieved a TO while 69.1% failed to achieve a TO most commonly because of postoperative complications. On multivariable analysis, factors associated with achieving a TO were age <65 years (OR: 1.5), albumin ≥3.5 g/dl (OR: 5.7), receipt of HIPEC (OR: 4.5), PCI ≤14 (OR: 2.2), intravenous fluid volume ≤10,000 ml (OR: 2.1), blood loss ≤1000 ml (OR: 4.2) and operative time <7 h (OR: 1.9); while receipt of neoadjuvant therapy (OR: 0.7) and liver resection (OR: 0.4) were associated with not achieving a TO (all p < 0.05). TO was associated with improved overall survival (median 159 months vs 56 months, p < 0.01) even after controlling for confounders on Cox regression (hazard ratio: 2.5, p < 0.01). CONCLUSION: Among patients undergoing CRS ± HIPEC for PSM, failure to achieve a TO is common and independently associated with worse overall survival.

The Utility of Preoperative Tumor Markers in Peritoneal Carcinomatosis from Primary Appendiceal Adenocarcinoma: an Analysis from the US HIPEC Collaborative.

BACKGROUND: Prognostication based on preoperative clinical factors is lacking in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study aims to determine the value of preoperative tumor markers as predictors of progression-free survival (PFS) and overall survival (OS) for patients with peritoneal carcinomatosis from a primary mucinous adenocarcinoma of the appendix (MACA). METHODS: We queried the United States HIPEC Collaborative, a database of patients with peritoneal carcinomatosis treated with CRS/HIPEC at twelve institutions between 2000 and 2017, identifying 409 patients with MACA. Multivariate analysis was used to identify independent predictors of disease progression. Subgroup analysis was conducted to evaluate the impact of tumor grade on the predictive value of tumor markers. RESULTS: CA19-9 [HR 2.44, CI 1.2-3.4] emerged as an independent predictor of PFS while CEA [HR 4.98, CI 1.06-23.46] was independently predictive of OS (p <0.01). Tumor differentiation was the most potent predictor of both PFS (poorly differentiated vs well, [HR 4.5 CI 2.01-9.94]) and OS ([poorly differentiated vs well-differentiated: [HR 13.5, CI 3.16-57.78]), p <0.05. Among patients with combined CA19-9 elevation and poorly differentiated histology, 86% recurred within a year of CRS/HIPEC (p < 0.01). Similarly, the coexistence of CEA elevation and unfavorable histology led to the lowest survival rate at two years [36%, p < 0.01]. CA-125 was not predictive of PFS or OS. CONCLUSION: Elevated preoperative CA19-9 portends worse PFS, while elevated CEA predicts worse OS after CRS/HIPEC in patients with MACA. This study provides additional evidence that CA19-9 and CEA levels should be collected during standard preoperative bloodwork, while CA-125 can likely be omitted. Tumor differentiation, when added to preoperative tumor marker levels, provides powerful prognostic information. Prospective studies are required to confirm this association.

Impact of Neoadjuvant Chemotherapy on the Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Multi-Institutional Retrospective Review.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000-2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.

Should We Be Doing Cytoreductive Surgery with HIPEC for Signet Ring Cell Appendiceal Adenocarcinoma? A Study from the US HIPEC Collaborative.

BACKGROUND: Appendiceal adenocarcinoma with signet ring cells (SCA) is associated with worse overall survival (OS), and it is unclear whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) should be pursued in this patient population. We assessed the prognostic implications of signet ring cells in patients with appendiceal adenocarcinoma and peritoneal carcinomatosis undergoing CRS-HIPEC. METHODS: The US HIPEC Collaborative, a 12-center, multi-institutional database of patients undergoing CRS-HIPEC, was reviewed for patients with SCA. Univariate and multivariate analyses were performed. RESULTS: Of 514 patients undergoing CRS-HIPEC for appendiceal adenocarcinoma, 125 (24%) had SCA. The SCA and non-SCA groups had similar baseline characteristics. SCA had worse OS compared with non-SCA (32.0 vs 91.4 months, p < 0.001). In univariate analysis for only SCA cases, there was worse OS in patients with poorly differentiated tumors, positive lymph nodes, LVI, PCI > 20, or incomplete cytoreduction (CC-2/3). However, multivariate analysis showed only positive lymph nodes (HR 1.14 [95% CI 1.00-1.31], p = 0.04), poor differentiation (5.60 [1.29-24.39], p = 0.02), and incomplete cytoreduction (4.90 [1.11-12.70], p = 0.03) were independently associated with decreased OS for SCA. CONCLUSION: While signet cells are a negative prognostic feature, they should not be a contraindication to CRS-HIPEC in patients with well-moderately differentiated tumors with negative lymph nodes, where complete cytoreduction can be achieved.

Readmissions After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: a US HIPEC Collaborative Study.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) results in significant morbidity and readmissions. Previous studies have been limited by single-institution design or lack of tumor details in the database used. METHODS: The 12-institution US HIPEC Collaborative Database was queried between 1999 and 2017. Preoperative and intraoperative patient and tumor details were analyzed for associations with readmissions. RESULTS: A total of 2017 of 2372 cases were included in the analysis. The 30-day readmission rate was 15.9% (n = 321). Common indications for readmission included failure to thrive (29.9%), infection (23.6%), and ileus/bowel obstruction (15.1%). The readmitted cohort had more complications, including intra-abdominal abscess (21.2% vs 6.2%), ileus (28.0% vs 17.2%), anastomotic leak (11.2% vs 2.2%), enteric fistula (5.6% vs 1.5%), deep venous thrombosis (6.2% vs 2.5%), and pulmonary embolism (6.9% vs 2.5%). Factors independently associated with readmission (p < 0.05) included ECOG score ≥ 3 (OR 3.4), depression (OR 2.4), total parenteral nutrition (OR 3.6), low anterior resection or partial colectomy (OR 2.0), and stoma creation (OR 2.2). Factors not associated included neoadjuvant chemotherapy, peritoneal cancer index, and completeness of cytoreduction. Readmission rate between 31 and 90 days was 3.9% (n = 78). Independent predictors (p < 0.05) included operative time (OR 1.1), low anterior resection or partial colectomy (OR 1.7), and stoma creation (OR 2.2). CONCLUSIONS: In the largest study to date examining readmissions after CRS-HIPEC, 30-day readmission rate was 15.9%. Tumor factors failed to predict readmission, whereas preoperative functional status and depression along with individual cytoreductive procedures predicted readmission. Patients with these risk factors or postoperative complications may benefit from closer post-discharge monitoring.

Comparison of open and closed hyperthermic intraperitoneal chemotherapy: Results from the United States hyperthermic intraperitoneal chemotherapy collaborative.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis can be performed in two ways: Open or closed abdominal technique. AIM: To evaluate the impact of HIPEC method on post-operative and long-term survival outcomes. METHODS: Patients undergoing CRS with HIPEC from 2000-2017 were identified in the United States HIPEC collaborative database. Post-operative, recurrence, and overall survival outcomes were compared between those who received open vs closed HIPEC. RESULTS: Of the 1812 patients undergoing curative-intent CRS and HIPEC, 372 (21%) patients underwent open HIPEC and 1440 (79%) underwent closed HIPEC. There was no difference in re-operation or severe complications between the two groups. Closed HIPEC had higher rates of 90-d readmission while open HIPEC had a higher rate of 90-d mortalities. On multi-variable analysis, closed HIPEC technique was not a significant predictor for overall survival (hazards ratio: 0.75, 95% confidence interval: 0.51-1.10, P = 0.14) or recurrence-free survival (hazards ratio: 1.39, 95% confidence interval: 1.00-1.93, P = 0.05) in the entire cohort. These findings remained consistent in the appendiceal and the colorectal subgroups. CONCLUSION: In this multi-institutional analysis, the HIPEC method was not independently associated with relevant post-operative or long-term outcomes. HIPEC technique may be left to the discretion of the operating surgeon.

What is the Optimal Preoperative Imaging Modality for Assessing Peritoneal Cancer Index? An Analysis From the United States HIPEC Collaborative.

BACKGROUND: Radiographic prediction of peritoneal carcinomatosis index (PCI) can improve patient selection for cytoreductive surgery. We aimed to determine the correlation of computed tomography (CT)-predicted PCI (CT-PCI) and magnetic resonance imaging (MRI)-predicted PCI (MRI-PCI) with intraoperative-PCI, and if a preoperative-PCI cutoff is associated with incomplete cytoreduction. PATIENTS AND METHODS: Patients from the US HIPEC Collaborative (2000-2017) with appendiceal, colorectal, or peritoneal mesothelioma (PM) histology who underwent cytoreductive surgery were included. Pearson correlation coefficients were used to determine correlation between preoperative and intraoperative-PCI values. Fisher r-to-z transformation was used to compare correlations. RESULTS: A total of 488 patients were included. Of these, 34% had noninvasive appendiceal, 30% invasive appendiceal, 28% colorectal, and 8% PM histology. CT-PCI was correlated with intraoperative-PCI for patients with noninvasive and invasive appendiceal and colorectal histologies (r = 0.689, 0.554, and 0.571; all P < .001), but not PM (r = 0.188; P = .295). MRI-PCI was correlated with intraoperative-PCI for all histologies (non-invasive appendiceal: r = 0.591; P = .002; invasive appendiceal: r = 0.848; P < .001; colorectal: r = 0.729; P < .001; PM: r = 0.890; P = .007). Comparing CT and MRI, correlations were similar in noninvasive appendiceal and colorectal histologies; MRI was better for invasive appendiceal and PM (P = .005 and P = .021, respectively). Twenty-eight (6%) patients underwent an incomplete cytoreduction (cytoreduction score, 2-3). PCI greater than 15 was associated with cytoreduction score of 2 to 3 for both CT and MRI (CT-PCI: odds ratio, 3.0; P = .033; MRI-PCI: odds ratio, 7.6; P = .071). CONCLUSIONS: In this multi-institutional cohort, CT and MRI-PCI correlate well with intraoperative-PCI. MRI appears to be superior for invasive appendiceal and peritoneal mesothelioma. External validation in a larger population is needed.

Prophylactic Versus Therapeutic Mastectomy: A Contemporary Analysis of the ACS-NSQIP Database.

INTRODUCTION: The objective of the study was to evaluate the morbidity, mortality, and postoperative outcomes associated with simple or subcutaneous mastectomy in the management of prophylactic versus therapeutic resection. In this study we aimed to assess if simple or subcutaneous mastectomy for prophylaxis affects perioperative outcomes compared with resection performed for biopsy proven malignancy. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for subjects who underwent simple or subcutaneous mastectomy between 2007 and 2012. Patient demographic characteristics, comorbid conditions, and postoperative complications were analyzed. RESULTS: Of the 30,803 patients, 30,644 (99.5%) underwent therapeutic mastectomy and 159 (0.5%) underwent prophylactic mastectomy. Subjects who underwent prophylactic surgery were more likely to be younger (45 vs. 58 years; P < .01) and white (134 [84%] vs. 20,647 [67%]; P < .01). Surgery time was significantly greater in the prophylactic group (265 vs. 166 minutes; P < .01). There was no significant difference in mortality between groups. There was a trend toward greater 30-day morbidity (15 [9%] vs. 1835 [6%]; P = .09) and occurrence of deep venous thrombosis (DVT; 2 [1%] vs. 74 [0.2%]; P = .06) in those who underwent prophylactic mastectomy. After age adjustment, the prophylactic group showed a nearly sixfold increase in DVT (odds ratio [OR], 5.77; 95% confidence interval [CI], 1.37-24.22), which persisted when controlling for surgery time (OR, 4.95; 95% CI, 1.18-20.86). CONCLUSION: Prophylactic simple or subcutaneous mastectomy incurs significant additional 30-day postoperative morbidity related to perioperative DVT. Risk-mitigating strategies should be considered in the perioperative care of this patient population.