Most patients who have colorectal cancer peritoneal metastases (CRC-PM) treated with cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy (CRS±HIPEC) experience recurrence within 1 year. This study assessed the safety and oncologic value of secondary CRS±HIPEC for patients with CRC-PM. A multi-institutional database of patients treated for CRC-PM (2000–2024) was reviewed. Patients who underwent curative-intent initial CRS±HIPEC alone were compared with those who underwent secondary CRS±HIPEC for recurrent disease. Patients who received more than two procedures were excluded. The primary objective was to evaluate the safety of secondary CRS±HIPEC for CRC-PM as measured by perioperative outcomes. The secondary objective was to examine the association between overall survival (OS) and secondary CRS±HIPEC. The study included 136 patients, 17 of whom underwent secondary CRS±HIPEC. There was no difference in postoperative complications between secondary and initial CRS±HIPEC. When OS was defined from the date of the index operation, secondary CRS±HIPEC was associated with improved OS versus initial CRS±HIPEC alone (51.0 months [95

Malignant gastrointestinal obstruction (MGIO), a frequent complication of peritoneal surface malignancies (PSM), often portends a poor prognosis. The lack of high-quality evidence on optimal management strategies necessitated a national consensus to address this clinical problem. A clinical management pathway was designed through a Delphi consensus process with national experts in peritoneal disease. Two rounds of voting were conducted to assess agreement levels with pathway blocks. Supporting evidence regarding procedural interventions for MGIO underwent evaluation via a rapid literature review. Of 111 participants responding in the first round, 90 (81

IntroductionLow grade appendiceal mucinous neoplasms (LAMN) are indolent tumors that lack invasive potential but may present as pseudomyxoma peritonei. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) significantly improves both overall and recurrence free survival. While systemic chemotherapy is generally considered ineffective for LAMN, little literature is available to support this notion. We evaluated outcomes for individuals with LAMN who did and did not receive systemic chemotherapy in combination with CRS+HIPEC.MethodsA multicenter retrospective cohort study was performed using the US HIPEC Collaborative that included patients with LAMN who underwent CRS+HIPEC. The overall survival (OS) and recurrence-free survival (RFS) of patients who did and did not receive systemic chemotherapy were compared. Survival and variables associated with survival were evaluated with the Kaplan-Meier analysis and cox regression, respectively.ResultsAmong the 529 included patients with LAMN, 63 (11.9%) received systemic chemotherapy and CRS+HIPEC, while 466 (88.1%) were treated with only CRS+HIPEC. Patients selected for systemic chemotherapy had a higher burden of disease (mean peritoneal cancer index: 18.8 +/- 8.6 versus 14.3 +/- 8.8, p<0.001). Patients who were not treated with chemotherapy had better mean OS and RFS (OS: 104.3 +/- 6.2 months, RFS: 84.9 +/- 6.6 months) compared to those who underwent systemic chemotherapy (OS: 70.2 +/- 6.8 months, RFS: 38 +/- 5.9 months, p<0.001). Increasing pre-operative CEA level (HR 1.012, p<0.001), higher completeness of cytoreduction score (reference CCR 0, CCR2 HR 34.175, p=0.001 and CCR3 HR 52.041, p=0.001), and treatment with systemic chemotherapy (HR 4.196, p=0.045) were associated with worse OS.ConclusionsIn this multicenter retrospective study, the receipt of perioperative chemotherapy was associated with worse long-term outcomes among patients with LAMN undergoing CRS-HIPEC. Systemic chemotherapy may lead to patient deconditioning and contribute to worse long-term outcomes. It should not be recommended outside of a clinical trial.

Background Enhanced Recovery After Surgery (ERAS) protocols have markedly improved outcomes after colorectal and other major surgery, suggesting benefits also for complex surgeries like Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC). This study investigates the adoption and acceptance of the recent ERAS recommendations for CRS-HIPEC within expert centers. Methods Clinicians from 16 expert centers across 9 countries were invited to answer an online survey inquiring about current clinical practice. Adoption of the 72 ERAS items from the recent dedicated guidelines were evaluated using a Likert-type scale with focus on preoperative, perioperative, and postoperative phases. Results Overall, 27 clinicians (11 female, 21 surgeons, 2 gynecologists and 4 anesthesiologists/intensivists) participated, with high adoption of ERAS protocols at baseline (67 %). More than half of the guideline items (54 %) were widely adopted. However, despite nearly 18 % intending to change their practices, there remains substantial resistance to further adoption, such as for measures like alcohol cessation programs, mechanical bowel preparation, and oral antibiotic decontamination. Barriers identified include resource limitations(20 %), perceived irrelevance (17 %) for specific patient groups, unclear benefits (59 %), and restrictive policies (5 %). Conclusion The study shows that most ERAS principles are routinely implemented in CRS-HIPEC surgeries, despite significant challenges with specific components and complex processes. Future research will focus on generating additional evidence and streamlining ERAS guidelines to prioritize essential elements.

Background: There is a critical need for contemporary education to address peritoneal surface malignancies (PSM). This study delineates the development of an online PSM curriculum for surgical trainees, in conjunction with a national consortium. Methods: A needs assessment survey was administered to attending surgical oncologists and trainees within the consortium, with a focus on current educational practices and preferences for PSM training. The identified focus areas informed the formulation of specific learning objectives and content. Results: The survey was completed by of 86/171 (48.5%) attending surgical oncologists in the group and 70 surgical trainees (56 residents and 14 fellows) from 31 unique institutions. Attending surgical oncologists emphasized trainee familiarity with general PSM principles and peritoneal metastases from lower gastrointestinal and gastric cancers when compared to gynecologic cancers and uncommon primaries (p < 0.001). Attending expectations increased incrementally with the trainee level in the knowledge and patient care domains. Attendings and trainees identified didactics and textbooks as primary modes of learning, although trainees reported using mobile learning tools more frequently. Disease site-specific educational content aligned with learning objectives was uploaded to a previously piloted online learning management system. Clinical management pathways and rotation guides were integrated to enhance the clinical applicability and consistency. Conclusions: Designing a PSM curriculum tailored to the educational needs of both attendants and trainees is feasible by using established pedagogical methods. This study provides a framework for teaching about complex diseases with limited educational literature.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis work was supported partially by the Teaching Innovation Project Grant awarded by Yale University Center for Teaching and Learning to VVB, FG, DS, and KKT.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesData from this study may be made available upon reasonable request from qualified medical or scientific professionals, provided that the request aligns with the specified purpose and may involve de-identified individual participant data. Access to the requested data is granted after signing a data-access agreement.

Peritoneal carcinomatosis carries a grim survival prognosis with complications ranging from the physical to the psychological. Cytoreductive surgery and infusion of heated intraperitoneal chemotherapy have evolved to become a commonly used treatment option in the multi-modal management of peritoneal carcinomatosis. Here, we examine the origins of surgery over a century ago as a potential cure for peritoneal carcinomatosis and how it has evolved with our knowledge of the disease to its present state. The origin of chemotherapy is similarly described as well as its progressive application in regional therapy, guided by the ongoing development of new agents, better understanding of peritoneal physiology, and improved systemic treatment. We show how these modalities began to be used in tandem, and standardized, leading to randomized trials and better understanding of the possibilities and limitations of treatment. Finally, we discuss the current status of patient selection for cytoreduction and future directions of intraperitoneal chemotherapy.

Peritoneal surface oncology (PSO) is a novel field dealing with the knowledge of peritoneal neoplasms, primary or secondary, and their clinical management. As a specific treatment with curative intent for peritoneal neoplasms developed over the years, there is a growing need to comprehensively educate and train surgical oncologists worldwide in this discipline, a recognized unmet need. The European School of Peritoneal Surface Oncology (ESPSO) emerged in 2014 to provide an answer to this need.

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.

Introduction We explored the association between weekend discharge and 30- and 90-d readmission rates in patients undergoing hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal carcinomatosis. Methods The US HIPEC Collaborative database, comprised of a longitudinal cohort of patients undergoing CRS/HIPEC for peritoneal carcinomatosis at twelve academic institutions between 2000 and 2017, was queried for date of discharge information. Patients were retrospectively divided into weekday and weekend/holiday discharge groups. Patients <18 y old, lacking day of discharge information, or who experienced intraoperative/in-hospital mortality were excluded. Comparisons were made between patients discharged on a weekday versus those discharged on a weekend or major holiday. Results 1415 patients met inclusion criteria for the study: 1108 (78%) patients with a weekday discharge and 308 (22%) with a weekend/holiday discharge. Median age at time of surgery was 55 y (Interquartile Range: 46-63); 59% (n = 841) patients were female, 25% (n = 328) of patients had high volume disease (defined as a peritoneal cancer index >20 intraoperatively), and 92% (n = 1210) of patients had a complete cytoreduction (defined as a completeness of cytoreduction score of 0 or 1). Overall, 15% (n = 218) of patients were readmitted within 30 d and 19% (n = 265) within 90 d. In a linear mixed effects model, weekend discharge was not associated with higher 30- or 90-d readmissions (P = 0.291, P = 0.743). Conclusions Weekend discharges are safe following CRS/HIPEC. Length of stay initiatives should focus on discharging the patient when medically ready, rather than avoiding weekend discharge out of an abundance of caution.

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.

INTRODUCTION:In patients with disseminated appendiceal cancer (dAC) who underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), characterizing and predicting those who will develop early recurrence could provide a framework for personalizing follow-up. This study aims to: (1) characterize patients with dAC that are at risk for recurrence within 2 y following of CRS ± HIPEC (early recurrence; ER), (2) utilize automated machine learning (AutoML) to predict at-risk patients, and (3) identifying factors that are influential for prediction. METHODS:A 12-institution cohort of patients with dAC treated with CRS ± HIPEC between 2000 and 2017 was used to train predictive models using H2O.ai's AutoML. Patients with early recurrence (ER) were compared to those who did not have recurrence or presented with recurrence after 2 y (control; C). However, 75% of the data was used for training and 25% for validation, and models were 5-fold cross-validated. RESULTS:A total of 949 patients were included, with 337 ER patients (35.5%). Patients with ER had higher markers of inflammation, worse disease burden with poor response, and received greater intraoperative fluids/blood products. The highest performing AutoML model was a Stacked Ensemble (area under the curve = 0.78, area under the curve precision recall = 0.66, positive predictive value = 85%, and negative predictive value = 63%). Prediction was influenced by blood markers, operative course, and factors associated with worse disease burden. CONCLUSIONS:In this multi-institutional cohort of dAC patients that underwent CRS ± HIPEC, AutoML performed well in predicting patients with ER. Variables suggestive of poor tumor biology were the most influential for prediction. Our work provides a framework for identifying patients with ER that might benefit from shorter interval surveillance early after surgery.

BACKGROUND:The AJCC 8th edition stratifies stage IV disseminated appendiceal cancer (dAC) patients based on grade and pathology. This study was designed to externally validate the staging system and to identify predictors of long-term survival.METHODS:A 12-institution cohort of dAC patients treated with CRS ± HIPEC was retrospectively analyzed. Overall survival (OS) and recurrence-free survival (RFS) were analyzed by using Kaplan-Meier and log-rank tests. Univariate and multivariate cox-regression was performed to assess factors associated with OS and RFS.RESULTS:Among 1009 patients, 708 had stage IVA and 301 had stage IVB disease. Median OS (120.4 mo vs. 47.2 mo) and RFS (79.3 mo vs. 19.8 mo) was significantly higher in stage IVA compared with IVB patients (p < 0.0001). RFS was greater among IVA-M1a (acellular mucin only) than IV M1b/G1 (well-differentiated cellular dissemination) patients (NR vs. 64 mo, p = 0.0004). Survival significantly differed between mucinous and nonmucinous tumors (OS 106.1 mo vs. 41.0 mo; RFS 46.7 mo vs. 21.2 mo, p < 0.05), and OS differed between well, moderate, and poorly differentiated (120.4 mo vs. 56.3 mo vs. 32.9 mo, p < 0.05). Both stage and grade were independent predictors of OS and RFS on multivariate analysis. Acellular mucin and mucinous histology were associated with better OS and RFS on univariate analysis only.CONCLUSIONS:AJCC 8th edition performed well in predicting outcomes in this large cohort of dAC patients treated with CRS ± HIPEC. Separation of stage IVA patients based on the presence of acellular mucin improved prognostication, which may inform treatment and long-term, follow-up strategies.

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.

Naked plasmid DNA (pDNA) and short interfering RNA (siRNA) duplexes were transduced into adult murine heart by means of sonoporation using the third-generation microbubble, BR14. Plasmid DNAs carrying luciferase, β-galactosidase (β-gal), or enhanced green fluorescent protein (EGFP) reporter genes were mixed with BR14 and injected percutaneously into the left ventricular (LV) cavity of C57BL/6 mice while exposed to transthoracic ultrasound at 1MHz for 60s. Sonoporation at an output intensity of 2.0W/cm2 and a 50% pulse duty ratio resulted in the highest luciferase expression in the heart. Histological examinations revealed significant expression of the β-gal and EGFP reporters in the subendocardial myocardium of LV. Intraventricular co-injection of siRNA-GFP and BR14 with concomitant ultrasonic exposure resulted in substantial reduction in EGFP expression in the coronary artery in EGFP transgenic mice. The present method may be applicable to gain-of-function and loss-of-function genetic engineering in vivo of adult murine heart.

The long-term prognosis of patients who undergo cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies (PSM) varies considerably on the basis of histological and operative factors. While overall survival (OS) estimates are used to inform adjuvant therapy and surveillance strategies, conditional survival may provide more clinically relevant estimates of prognosis by accounting for disease-free time elapsed. All patients from 12 academic institutions who underwent CRS ± HIPEC for PSM from 2000 to 2017 were retrospectively analyzed. OS and disease-free survival (DFS) rates were calculated using the Kaplan–Meier method while conditional overall (COS) and conditional disease-free survival (CDFS) rates were calculated at 1, 2, or 3 years from surgery for different tumor histologies. Overall, 1610 patients underwent CRS ± HIPEC. Among patients with benign appendiceal mucinous tumors (N = 460), 5-year OS and COS at 3 years were 92.1% and 96.3% (Δ4.2%), respectively. For patients with well-differentiated appendiceal cancers (N = 400), 5-year OS and COS at 3 years were 76.3% and 88.3% (Δ12.0%), respectively. For patients with high-grade appendiceal cancers (N = 258), 5-year OS and COS at 3 years were 43.8% and 75.4% (Δ31.6%), respectively. For patients with colorectal cancers (N = 362), 5-year OS and COS at 3 years were 31.8% and 67.3% (Δ35.5%), respectively. For patients with peritoneal mesothelioma (N = 130), 5-year OS and COS at 3 years were 67.6% and 89.7% (Δ22.1%), respectively. Similar trends were observed for DFS/CDFS. The conditional survival of patients undergoing CRS ± HIPEC for PSM is associated with tumor histology. COS and CDFS provide a more accurate, dynamic estimate of survival than OS and DFS, especially for patients with more aggressive histologies.

BackgroundCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is increasingly performed for peritoneal surface malignancies but remains associated with significant morbidity. Scant research is available regarding the impact of insurance status on postoperative outcomes. MethodsPatients undergoing CRS/HIPEC between 2000 and 2017 at 12 participating sites in the US HIPEC Collaborative were identified. Univariate and multivariate analyses were used to compare the baseline characteristics, operative variables, and postoperative outcomes of patients with government, private, or no insurance. ResultsAmong 2268 patients, 699 (30.8%) had government insurance, 1453 (64.0%) had private, and 116 (5.1%) were uninsured. Patients with government insurance were older, more likely to be non-white, and comorbid (p < 0.05). Patients with government (OR: 2.25, CI: 1.50-3.36, p < 0.001) and private (OR: 1.69, CI: 1.15-2.49, p = 0.008) insurance had an increased risk of complications on univariate analysis. There was no independent relationship on multivariate analysis. An American Society of Anesthesiologists score of 3 or 4, peritoneal carcinomatosis index score >15, completeness of cytoreduction score >1, and nonhome discharge were factors independently associated with a postoperative complication. ConclusionWhile there were differences in postoperative outcomes between the three insurance groups on univariate analysis, there was no independent association between insurance status and postoperative complications after CRS/HIPEC.