Development and Validation of Nomograms to Predict Survival in Patients Undergoing Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin.

Importance: Pseudomyxoma peritoni, a rare condition characterized by mucinous ascites and peritoneal deposits, mainly originates from a ruptured mucinous appendix tumor and is considered an indolent disease but can progress and become fatal. Optimal treatment to improve cure and survival rates involves complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Accurate predictive models are useful in supporting and informing treatment strategies and stratifying patient follow-up. Objective: To evaluate the prognostic significance of clinically important variables and generate validated nomograms to predict overall (OS) and disease-free survival (DFS) following CCRS and hyperthermic intraperitoneal HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin. Design, Setting, and Participants: This retrospective study used prospectively collected data on patients who had cytoreductive surgery (CRS) and HIPEC in a single institution between 1994 and 2018. The cohort was randomly allocated into development (70%) and validation (30%) sets. Univariate and multivariate analyses were performed with Cox proportional hazards regression. Main Outcomes and Measures: A prediction model was developed with significant prognostic factors identified by multivariate analysis. The model's prognostic performance was evaluated with the concordance index (C index). The nomogram was calibrated by comparing the predicted and observed probabilities. Results: Of 2637 CRS and HIPEC operations, 1102 patients (female, 64.4%; median age [IQR], 57.0 [48.0-66.0] years) (41.8%) had CCRS for PMP of appendiceal origin. Elevated tumor markers, peritoneal carcinomatosis index, gastrectomy, and tumor grade were independent predictive factors for DFS. Gender, age, elevated tumor makers, peritoneal carcinomatosis index, and tumor grade influenced OS. The nomograms were generated with respective prognostic factors. The nomograms showed good performance in predicting survival. Median OS of the cohort was 16.5 years (95% CI, 13.7-19.2) with a 5-year probability of survival of 80.2%. The median DFS was 10.3 years (95% CI, 7.2- 13.3) and the 5-year probability of recurrence-free survival was 60.5%. Conclusions and Relevance: Clinically important independent predictors for survival and recurrence were selected to develop the nomograms for OS and DFS. These 2 nomograms are user friendly and useful tools for patient management with clinical trial design applications.

Laparoscopic versus open resection for rectal cancer: An individual patient data meta analysis of randomized controlled trials.

BACKGROUND AND AIMS: The role of laparoscopic rectal cancer resection remains controversial. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer. METHODS: Medline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. RESULTS: Seven randomized trials involving 1767 laparoscopic and 1293 open resections for rectal cancer were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78-1.06, p = 0.241) and 0.86 (95% CI:0.73-1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI:0.54-0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI:0.55-0.99, p = 0.041). CONCLUSIONS: This meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer.

Indications and long-term outcomes of preoperative inferior vena caval filters in 111 patients at high risk of pulmonary embolism undergoing major abdominal surgery.

AIMS: Patients with abdominal cancer requiring major surgical intervention are at high risk of venous thromboembolic events (VTE), particularly pulmonary emboli (PE). A proportion of patients with cancer can present with, or have had, major VTEs prior to definitive surgical treatment. Preoperative percutaneous inferior venal caval filters (IVCF) may reduce the risk of PE. The aim of this study was to assess the indications, complications, retrieval rates, and long-term outcome of IVCFs in patients undergoing major abdominal surgery. METHODS: This was a retrospective analysis of a prospective IVCF database between 2007 and 2018 of all patients with IVCF insertion prior to major abdominal surgery. The indications for an IVCF, procedural complications and surgical interventions were recorded. RESULTS: Overall, 111 patients had IVCF insertion. IVCF placement failed in one patient with gross abdominal disease. Indications for an IVCF were: prior PE in 65/111 (59%) and major vein thrombus in 42 (38%). Overall, 26/111 (23%) had the IVCF removed at a median of 91 days. In two patients IVCF removal failed. At follow-up of the 85 patients who had the IVCF left in situ, six developed filter-related thrombus and 13 a deep vein thrombosis (DVT). Four patients had a PE with an indwelling IVCF. CONCLUSION: Preoperative IVCF may reduce perioperative PE in patients at high risk of thrombosis undergoing major abdominal surgery where early anticoagulation is contraindicated. Long-term follow-up of retained IVCF suggests that major problems are infrequent, though further thrombosis may occur and long-term anticoagulation may be needed.

Managing Recurrent Pseudomyxoma Peritonei in 430 Patients After Complete Cytoreduction and HIPEC: A Dilemma for Patients and Surgeons.

BACKGROUND: Epithelial appendiceal neoplasms are uncommon peritoneal malignancies causing a spectrum of disease including pseudomyxoma peritonei (PMP). The optimal management is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite complete CRS (CCRS), recurrence develops in almost 45% of patients. No consensus exists for the optimal treatment of recurrent disease, with treatment strategies including repeat CRS, watch-and-wait, and palliative chemotherapy. This report aims to describe evolving management strategies for a large cohort with recurrence after CCRS. METHODS: This retrospective study analyzed a prospective database of patients with recurrence after CCRS for appendiceal neoplasms from 1994 to 2017 who had long-term follow-up evaluation with tumor markers and computed tomography (CT). RESULTS: Overall, 430 (37.6%) of 1145 PMP patients experienced recurrence at a median of 19 months. Of these 430 patients 145 (33.7%) underwent repeat CRS, 119 (27.7%) had a watch-and-wait approach, and 119 (27.7%) had palliative chemotherapy. The patients with recurrence had a median overall survival (OS) of 39 months, a 3-year survival of 74.6%, a 5-year survival of 57.4%, and a 10-year survival of 36.5%. In the multivariate analysis, the patients who had recurrence within 1 year after primary CRS (hazard ratio [HR], 3.55), symptoms at recurrence (HR, 3.08), a high grade of disease or adenocarcinoma pathology (HR, 2.94), signet ring cells (HR, 1.91), extraperitoneal metastatic disease (HR, 1.71), or male gender (HR, 1.61) had worse OS. The OS was longer for the patients who had repeat CRS (HR, 0.41). The patients who underwent repeat CCRS had a 3-year OS of 87.5%, a 5-year OS of 78.1%, and a 10-year OS of 67.9%. CONCLUSIONS: Dilemmas persist around the optimal management of patients with recurrence after CRS and HIPEC for appendiceal tumors. Selected patients benefit from repeat CRS, particularly those with favorable tumor biology and focal disease.

The Role of Hyperthermic Intraperitoneal Chemotherapy in Pseudomyxoma Peritonei After Cytoreductive Surgery.

Importance: Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available. Objectives: To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP. Design, Setting, and Participants: This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018. Interventions: HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens. Main Outcomes and Measures: Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models. Results: Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P < .001; E-value, 2.03). Such prognostic advantage was associated with oxaliplatin plus fluorouracil-leucovorin (HR, 0.42; 95% CI, 0.19-0.93; P = .03) and cisplatin plus mitomycin (HR, 0.57; 95% CI, 0.42-0.78; P = .001) schedules. Conclusions and Relevance: In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.

Postoperative paralytic ileus after cytoreductive surgery combined with heated intraperitoneal chemotherapy.

BACKGROUND: Patients with peritoneal malignancy treated by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) are prone to develop postoperative paralytic ileus (POI). POI is associated with significant increase in both morbidity and mortality. CRS and HIPEC commonly result in prolonged POI (PPOI). The objective was to clarify the extent of PPOI in patients treated by CRS and HIPEC for peritoneal malignancy. METHODS: This was a prospective multicenter study including patients operated with CRS and HIPEC at the Department of Surgery, Aarhus University Hospital, Denmark and the Peritoneal Malignancy Institute, Basingstoke, United Kingdom. A total of 85 patients were included over 5 months. Patients prospectively reported parameters of postoperative gastrointestinal function in a diary from post-operative day 1 (POD1) until discharge. PPOI was defined as first defecation on POD6 or later. RESULTS: Median time to first flatus passage was 4 days (range 1-12). Median time to first defecation was 6 days (1-14). Median time to removal of nasojejunal tube was 4 days (3-13) and 7 days (1-43) for nasogastric tube. Forty-six patients (54%) developed PPOI. Patients with PPOI had longer time to first flatus (p<0.0001) and longer time to removal of nasojejunal tube (p=0.001). Duration of surgery correlated to time to first flatus (p=0.015) and time to removal of nasogastric or nasojejunal tube (p<0.0001) but not to time to first defecation (p=0.321). CONCLUSIONS: Postoperative gastrointestinal paralysis remains a common and serious problem in patients treated with CRS and HIPEC.