Continuous Wound Irrigation and Intraoperative Methadone Decreases Opioid Use and Shortens Length of Stay After CRS/HIPEC.

BACKGROUND: Epidural analgesia is resource and labor intense and may limit postoperative management options and delay discharge. This study compared postoperative outcomes after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with epidural analgesia versus continuous wound infusion system (CWIS) with/without intraoperative methadone. METHODS: A single-institution, retrospective chart review was performed including all patients undergoing open CRS/HIPEC from 2018 to 2021. Patient demographics, surgical characteristics, length of stay, and in-hospital analgesic use were reviewed. In-hospital opioid exposure in morphine milligram equivalents (MME) was calculated. Multivariate analysis (MVA) for mean total and daily opioid exposure was conducted. RESULTS: A total of 157 patients were included. Fifty-three (34%) had epidural analgesia, 96 (61%) had CWIS, and 79 (50%) received methadone. Length of stay was significantly shorter with CWIS + methadone versus epidural (7 vs. 8 days, p < 0.01). MVA showed significantly lower mean total and daily opioid exposure with CWIS+methadone versus epidural (total: 252.8 ± 17.7 MME vs. 486.8 ± 86.6 MME; odds ratio [OR] 0.72, 95% confidence interval [CI] 0.52-0.98, p = 0.04; Daily: 32.8 ± 2.0 MME vs. 51.9 ± 5.7 MME, OR 0.72, 95% CI 0.52-0.99, p ≤ 0.05). The CWIS-only group (n = 17) had a significantly lower median oral opioid exposure versus epidural (135 MME vs. 7.5 MME, p < 0.001) and longer length of stay versus CWIS + methadone (9 vs. 7 days, p = 0.04), There were no CWIS or methadone-associated complications and one epidural abscess. CONCLUSIONS: CWIS + methadone safely offers better pain control with less in-hospital opioid use, shorter length of stay, and decreased resource utilization compared with epidural analgesia in patients undergoing CRS-HIPEC.

Preoperative CA 19-9 Predicts Disease Progression in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: An Analysis from the US HIPEC Collaborative.

INTRODUCTION: Patients with colorectal peritoneal metastases (CRPM) are increasingly treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, data identifying preoperative risk factors for poor oncologic outcomes after this procedure are limited. We aimed to determine the prognostic value of preoperative CEA, CA 125, and CA 19-9 on disease progression after CRS/HIPEC. METHODS: Patients with CRPM treated with curative intent CRS/HIPEC from 12 participating sites in the United States from 2000 to 2017 were identified. Progression-free survival (PFS), defined as disease progression or recurrence, was the primary outcome. RESULTS: In 279 patients who met inclusion criteria, the rate of disease progression was 63.8%, with a median PFS of 11 months (interquartile range [IQR] 5-20). Elevated CA 19-9 was associated with dismal PFS at 2 years (8.9% elevated vs. 30% not elevated, p < 0.01). In 113 patients who underwent upfront CRS/HIPEC, CA 19-9 emerged as the sole tumor marker independently predictive of worse PFS (hazard ratio [HR] 2.88, p = 0.048). In the subgroup of patients who had received neoadjuvant therapy (NAT), no variable was independently predictive of PFS. CA 19-9 levels over 37 U/ml were highly specific for accelerated disease progression after CRS/HIPEC. Lastly, there was no association between PFS and elevated CEA or CA 125. CONCLUSIONS: Elevated CA 19-9 is associated with decreased PFS in patients with CRPM. While traditionally CEA is the main tumor marker assessed in colon cancer, we found that CA 19-9 may better inform preoperative risk stratification for poor oncologic outcomes in patients with CRPM. However, prospective studies are required to confirm this association.

Do Lymph Node Metastases Matter in Appendiceal Cancer with Peritoneal Carcinomatosis? A US HIPEC Collaborative Study.

BACKGROUND: Whether formal regional lymph node (LN) evaluation is necessary for patients with appendiceal adenocarcinoma (AA) who have peritoneal metastases is unclear. The aim of this study was to evaluate the prognostic value of LN metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: A retrospective analysis of the US HIPEC collaborative, a multi-institutional consortium comprising 12 high-volume centers, was performed to identify patients with AA who underwent CRS-HIPEC with adequate LN sampling (≥ 12 LNs). RESULTS: Two hundred-fifty patients with AA who underwent CRS-HIPEC were included. Outcomes were compared between LN - and LN + disease. Baseline patient characteristics between groups were similar, with most patients undergoing complete cytoreduction (0/1: 86.0% vs. 76.8%, p = 0.08), respectively. More adverse tumor factors were found in patients with LN + disease, including poor differentiation, signet ring cells, and lymphovascular invasion. Multivariate analysis of overall survival (OS) found LN + disease was independently associated with worse OS (HR: 2.82 95%CI: 1.25-6.34, p = 0.01), even after correction for receipt of systemic therapy. On Kaplan-Meier analysis, median OS was lower in patients with LN + disease (25.9 months vs. 91.4 months, p < 0.01). LN + disease remained associated with poor OS following propensity score matching (HR: 4.98 95%CI: 1.72-14.40, p < 0.01) and in patients with PCI ≥ 20 (HR: 3.68 95%CI: 1.54-8.80, p < 0.01). CONCLUSIONS: In this large multi-institutional study of patients with AA undergoing CRS-HIPEC, LN status remained associated with worse OS even in the setting of advanced peritoneal carcinomatosis. Formal LN evaluation should be performed for most patients with AA undergoing CRS-HIPEC.

Development and Validation of an Explainable Machine Learning Model for Major Complications After Cytoreductive Surgery.

Importance: Cytoreductive surgery (CRS) is one of the most complex operations in surgical oncology with significant morbidity, and improved risk prediction tools are critically needed. Machine learning models can potentially overcome the limitations of traditional multiple logistic regression (MLR) models and provide accurate risk estimates. Objective: To develop and validate an explainable machine learning model for predicting major postoperative complications in patients undergoing CRS. Design, Setting, and Participants: This prognostic study used patient data from tertiary care hospitals with expertise in CRS included in the US Hyperthermic Intraperitoneal Chemotherapy Collaborative Database between 1998 and 2018. Information from 147 variables was extracted to predict the risk of a major complication. An ensemble-based machine learning (gradient-boosting) model was optimized on 80% of the sample with subsequent validation on a 20% holdout data set. The machine learning model was compared with traditional MLR models. The artificial intelligence SHAP (Shapley additive explanations) method was used for interpretation of patient- and cohort-level risk estimates and interactions to define novel surgical risk phenotypes. Data were analyzed between November 2019 and August 2021. Exposures: Cytoreductive surgery. Main Outcomes and Measures: Area under the receiver operating characteristics (AUROC); area under the precision recall curve (AUPRC). Results: Data from a total 2372 patients were included in model development (mean age, 55 years [range, 11-95 years]; 1366 [57.6%] women). The optimized machine learning model achieved high discrimination (AUROC: mean cross-validation, 0.75 [range, 0.73-0.81]; test, 0.74) and precision (AUPRC: mean cross-validation, 0.50 [range, 0.46-0.58]; test, 0.42). Compared with the optimized machine learning model, the published MLR model performed worse (test AUROC and AUPRC: 0.54 and 0.18, respectively). Higher volume of estimated blood loss, having pelvic peritonectomy, and longer operative time were the top 3 contributors to the high likelihood of major complications. SHAP dependence plots demonstrated insightful nonlinear interactive associations between predictors and major complications. For instance, high estimated blood loss (ie, above 500 mL) was only detrimental when operative time exceeded 9 hours. Unsupervised clustering of patients based on similarity of sources of risk allowed identification of 6 distinct surgical risk phenotypes. Conclusions and Relevance: In this prognostic study using data from patients undergoing CRS, an optimized machine learning model demonstrated a superior ability to predict individual- and cohort-level risk of major complications vs traditional methods. Using the SHAP method, 6 distinct surgical phenotypes were identified based on sources of risk of major complications.

Communication in surgery: the therapy of hope.

Surgeons are frequently consulted for assistance in the palliative management of patients, and surgery is an essential tool in the armamentarium of comprehensive palliative care. Palliative surgical consults are some of the most challenging surgical consults, not only for technical reasons, but also because of the (usually) higher odds of morbidity or mortality, often in the setting of a limited life expectancy. Surgery is also often seen as the last possibility of hope, which can place a great emotional burden on the surgeon. Surgeons find themselves torn between concern about causing more harm than good, and not wanting to miss an opportunity to help. Although there is a growing body of literature around the outcomes for palliative surgery and patient selection, most palliative surgery decisions are still not evidence-based, but rather experienced-based. Because palliative surgical decision-making relies heavily on the surgeon's experience and risk (and/or regret) tolerance, surgeons often find themselves called upon to explain highly complex and nuanced concepts with existential outcomes to people who are desperate for hope. Even for the best communicators, achieving the goals of effective communication can be challenging in these situations, and in some instances, may seem unachievable. This article examines the communication challenges faced by surgeons in the palliative surgical setting and recommends specific strategies and approaches to help address those challenges and facilitate effective communication. Lastly, it considers the most necessary element of care for most patients and surgeons in the palliative setting: hope.

Current management of malignant bowel obstructions: a survey of acute care surgeons and surgical oncologists.

BACKGROUND: Malignant small bowel obstructions (MSBOs) are one of the most challenging problems surgeons encounter, and evidence-based treatment recommendations are lacking. We hypothesized that current opinions on MSBO management differ between acute care surgeons (ACSs) and surgical oncologists (SOs). METHODS: We developed three case scenarios describing patients with previously treated cancer who developed an MSBO. Each case had five to six alternate scenarios, intended to capture the heterogeneity of MSBO presentations. Members of the Society of Surgical Oncology, the American Society of Peritoneal Surface Malignancies, and the Eastern Association for the Surgery of Trauma were asked how likely they would be to offer surgical treatment in each scenario. Responses were analyzed for factors associated with the likelihood surgeons would offer surgical management. RESULTS: 316 surgeons completed the survey: 119 (37.7%) SOs and 197 (62.3%) ACSs. Overall, SOs were nearly twice as likely as ACSs to recommend surgical management. The largest differences between provider groups were seen in patients with an increased metastatic burden. In a patient with MSBO with metastatic colon cancer, both SOs (95.8%) and ACSs (94.4%) were likely or very likely to offer an operation (p=0.587); however, this fell to 91.6% and 77.7%, respectively, when this patient had multiple hepatic metastases (p=0.001). All surgeons were less likely to offer surgery to patients with multiple sites of obstruction, recurrent MSBO, and shorter disease-free intervals. DISCUSSION: Opinions on MSBO management differ based on surgeon training and experience. Multidisciplinary management of patients with MSBO should be offered when available and increased emphasis placed on determining optimal management guidelines across specialties. LEVEL OF EVIDENCE: Level IV Epidemiologic.

A Palliative Approach to Management of Peritoneal Carcinomatosis and Malignant Ascites.

In addition to severe, life-limiting complications such as malignant bowel obstruction, fistulae, and malignant ascites, peritoneal carcinomatosis frequently causes life-impacting symptoms such as pain, nausea, anorexia, cachexia, and fatigue. A variety of medical, interventional, and surgical therapies are now available for management of both complications and symptoms. Although surgery in this population is often associated with a relatively high risk of morbidity and mortality, operative intervention can offer effective palliative treatment in appropriately selected patients. Early involvement of palliative care specialists as part of a multidisciplinary team is essential to providing optimal, holistic care of patients with peritoneal carcinomatosis.

Drivers of Moral Distress in Surgical Intensive Care Providers: A Mixed Methods Study.

BACKGROUND: Moral distress is common among healthcare providers, leading to staff burnout and attrition. This study aimed to identify root causes of and potential solutions to moral distress experienced by surgical intensive care unit (SICU) providers. MATERIALS AND METHODS: This is a mixed methods study of physicians and nurses from a single, academic SICU. We obtained quantitative data from the Measures of Moral Distress for Healthcare Professionals (MMD-HP) survey and qualitative data from semi-structured interviews. The MMD-HP is a 27 question, validated survey on triggers of moral distress. Survey and interview data were analyzed to identify drivers of moral distress using a convergent design. RESULTS: 21 nurses and 25 physicians were surveyed and 17 providers interviewed. MMD-HP data demonstrated high levels of moral distress for nurses (mean total MMD-HP 132 ± 63.5) and physicians (121.7 ± 64.7), P = 0.68. The most frequent root cause of moral distress for all providers was participating in the delivery of aggressive care perceived to be futile. Nurses also reported caring for patients with unclear goals of care as a key driver of moral distress. Interview data supported these findings. Providers recommended improving access to palliative care to increase early communication on patient goals of care and end-of-life as a solution. Culture in the SICU often promotes supporting aggressive care however, acting as a potential barrier to increasing palliative resources. CONCLUSIONS: Providing aggressive care that is perceived as futile was the primary driver of moral distress in the SICU. Interventions to improve early communication and access to end-of-life care should be prioritized to decrease moral distress in staff.

Impact of Perioperative Blood Transfusions on Outcomes After Hyperthermic Intraperitoneal Chemotherapy: A Propensity-Matched Analysis.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major operation frequently necessitating red blood cell transfusion. Using multi-institutional data from the U.S. HIPEC Collaborative, this study sought to determine the association of perioperative allogenic blood transfusion (PABT) with perioperative outcomes after CRS/HIPEC. METHODS: This retrospective cohort study analyzed patients who underwent CRS/HIPEC for peritoneal surface malignancy between 2000 and 2017. Propensity score-matching was performed to mitigate bias. Univariate analysis was used to compare demographic, preoperative, intraoperative, and postoperative variables. Factors independently associated with PABT were identified using multivariate analysis. RESULTS: The inclusion criteria were met by 1717 patients, 510 (29.7%) of whom required PABT. The mean Peritoneal Cancer Index (PCI) of our cohort was 14.8 ± 9.3. Propensity score-matching showed an independent association between PABT and postoperative risk of pleural effusion, hemorrhage, pulmonary embolism, enteric fistula formation, Clavien-Dindo grades 3 and 4 morbidity, longer hospital stay, and reoperation (all P < 0.05 in the multivariate analysis). Compared with the patients who received 1 to 5 red blood cell (RBC) units, the patients who received more than 5 units had a greater risk of renal impairment, a longer intensive care unit (ICU) stay, and more postoperative infections. Finally, PABT was an independent predictor of worse survival for patients with appendiceal and colorectal primaries. CONCLUSION: Even low levels of PABT for patients undergoing CRS/HIPEC are independently associated with a greater risk of infectious and non-infectious postoperative complications, and this risk is increased for patients receiving more than 5 RBC units. Worse survival was independently predicted by PABT for patients with peritoneal carcinomatosis of an appendiceal or colorectal origin.

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.

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.

Institutional variation in recovery after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: An opportunity for enhanced recovery pathways.

BACKGROUND: Variations in care have been demonstrated both within and among institutions in many clinical settings. By standardizing perioperative practices, Enhanced Recovery After Surgery (ERAS) pathways reduce variation in perioperative care. We sought to characterize the variation in cytoreductive surgery (CRS)/heated intraperitoneal chemotherapy (HIPEC) perioperative practices among experienced US medical centers. METHODS: Data from the US HIPEC Collaborative represents a retrospective multi-institutional cohort study of CRS and CRS/HIPEC procedures performed from 12 major academic institutions. Patient characteristics and perioperative practices were reported and compared. Institutional variation was analyzed using hierarchical mixed-effects linear (continuous outcomes) or logistic (binary outcomes) regression models. RESULTS: A total of 2372 operations were included. CRS/HIPEC was performed most commonly for appendiceal histologies (64.2%). The rate of complications (overall 56.3%, range: 31.8-70.9) and readmissions (overall 20.6%, range: 8.9-33.3) varied by institution (P < .001). Institution-level variation in perioperative practice patterns existed among measured ERAS pathway process/outcomes (P < .001). The percentages of variation with each process/outcome measure attributable solely to institutional practices ranged from 0.6% to 66.6%. CONCLUSIONS: Significant variation exists in the perioperative care of patients undergoing CRS/HIPEC at major US academic institutions. These findings provide a strong rationale for the investigation of best practices in CRS/HIPEC patients.

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.

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.

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.

Heterogeneous mutational profile and prognosis conferred by TP53 mutations in appendiceal mucinous neoplasms.

The eighth edition of American Joint Committee on Cancer (AJCC) advocates a 3-tier grading system for appendiceal mucinous tumors. The mutational profile for each tumor grade and the impact of TP53 mutation on survival are unknown. We classified appendiceal mucinous tumors into 3 grades based on the eighth edition of American Joint Committee on Cancer: 21 G1 low-grade mucinous neoplasms, 21 G2 appendiceal adenocarcinomas, and 26 G3 signet ring cell carcinomas. Mutation profiles were obtained using next-generation sequencing. The impact of TP53 on prognosis was investigated by multivariable analysis. Most G1 tumors harbor KRAS/GNAS mutations with TP53 and SMAD4 in a small subset of cases. G2 and G3 tumors show a more complex mutation pattern carrying PIK3CA, BRAF, or TP53 mutations in addition to KRAS/GNAS. PTEN mutations were detected exclusively in G2 tumors. The prevalence of KRAS and GNAS mutations is significantly lower in G3 tumors relative to G1/G2, whereas TP53, PIK3CA, or BRAF mutations are common. Mutations in NRAS, IDH2, CDH1, RB1, CTNNB1, CDKN2A, PTPN11, and KIT genes were observed in single cases. Patients with TP53-mutated disseminated G2 and G3 tumors had worse progression-free survival than did those with wild-type TP53 tumors (P = .0315). A trend toward worse overall survival was observed in TP53-mutated G3 tumors (P = .102). p53 expression correlated with mutation status. We demonstrate a distinct but overlapping pattern of gene mutations in each grade of appendiceal mucinous tumors and the independent impact of TP53 mutation on progression-free survival but not overall survival.

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.