Intra- and Interpatient Drug Response Heterogeneity Exist in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Nongynecologic Cancers.

BACKGROUND: Select patients with peritoneal metastases are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We assayed for intra- and interpatient drug response heterogeneity through testing of patient-derived tumor organoids (PDTOs). METHODS: PDTOs were generated from CRS/HIPEC patients from December 2021 to September 2022 and subjected to an in vitro HIPEC drug screen. Drug response was assessed with a cell viability assay and cleaved caspase-3 staining. RESULTS: A total of 31 patients were consented for tissue collection. Viable tissue was harvested from 23, and PDTO generation was successful in 13 (56%). PDTOs were analyzed from six appendiceal, three colorectal, two small bowel, one gastric, and one adrenal tumor. Drug screen results were generated in as few as 7 days (62%), with an average time of 12 days. Most patients received mitomycin-C (MMC) intraoperatively (n = 9); however, in only three cases was this agent considered the optimal choice in vitro. Three sets of PDTOs were resistant (defined as > 50% PDTO viability) to all agents tested and two were pan-sensitive (defined as 3 or more agents with < 50% PDTO viability). In three patients, organoids were generated from multiple metastatic sites and intrapatient drug response heterogeneity was observed. CONCLUSIONS: Both intra- and interpatient drug response heterogeneity exist in patients undergoing CRS/HIPEC for nongynecologic abdominal cancers. Caution must be used when interpreting patient response to chemotherapeutic agents based on a single site of testing in those with metastatic disease.

Comparison of outcomes between surgical treatment of colorectal cancer metastatic to the liver and the peritoneum: Review of the literature.

BACKGROUND: Liver and peritoneum are two of the most common sites of colorectal metastases. METHODS: We searched for articles comparing outcomes of surgical management for metastatic colorectal cancer to the liver and peritoneum. CONCLUSION: Cytoreductive surgery/heated intraperitoneal chemotherapy has a similar safety profile and survival outcomes as hepatectomy for colorectal metastases after stratifying by resection status and should be incorporated earlier in the management algorithm for colorectal cancer patients with peritoneal metastases METHODS: We performed a wide search on PubMed, EMBASE, and Google Scholar for articles comparing outcomes of surgical management for metastatic colorectal cancer to the liver and peritoneum. We focused on studies comparing their perioperative clinical outcomes as well as their oncological outcomes. The following words were included in the search: comparison, outcomes, metastasectomy, colorectal cancer, liver, peritoneal surface disease, hepatectomy, and cytoreduction. RESULTS: One hundred and twenty studies were evaluated. Six of these studies met the criteria for this review.

Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still beneficial in patients diagnosed with colorectal peritoneal metastasis who underwent palliative chemotherapy?

BACKGROUND: With a 5-year overall survival of less than 5%, colorectal peritoneal metastasis (CPM) patients are often managed with palliative chemotherapy (CTx). In the past few decades, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced as a possible curative treatment for highly selective CPM patients. We share our experience of CRS and HIPEC given the unique characteristics of the medical system and the benefit of CRS and HIPEC in palliative setting. METHODS: From April 2017 to October 2021, CPM patients who underwent CRS and HIPEC were analyzed. Patients were allocated into perioperative and palliative CTx arm based on the duration between initial diagnosis of CPM to undergoing CRS and HIPEC of 6 months. Data including perioperative parameters, postoperative outcomes, and survival were analyzed with a median follow-up of 28.5 months. RESULTS: Twenty-six CPM patients underwent CRS and HIPEC. Mean time from diagnosis of CPM to CRS and HIPEC was 5.5 months with 14 patients in the perioperative arm and 12 patients in the palliative arm. Perioperative group showed a longer RFS of 13.5 months compared to 8 months in the palliative group. Median overall survival of palliative group was 41.50 months, and 18 patients among all groups are alive at the time of this report. CONCLUSION: CRS and HIPEC could be a treatment option for a carefully selected CPM patients performed by experienced surgeons. Overall survival of 41.50 months in palliative group compared to 16.8 months from conventional systemic CTx supports CRS and HIPEC even in palliative patients.

A case of pseudomyxoma peritonei arising from a perforated intraductal papillary mucinous neoplasm that underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Pseudomyxoma peritonei (PMP) of pancreatic origin arising from an intraductal papillary mucinous neoplasm (IPMN) is rare. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established as the optimal treatment for PMP. However, the benefits and safety of CRS with HIPEC for treating PMP of pancreatic origin remain unclear. Herein, we describe a case of PMP of pancreatic origin that was treated with CRS and HIPEC without postoperative complications. A 75-year-old woman was referred to our department. Computed tomography (CT) revealed a multilocular cystic tumor in the pancreatic tail, notable mucinous ascites in the abdominal cavity, and scalloping of the liver and spleen. CT did not reveal the appendix, and the ovaries were normal in size. The patient was diagnosed with PMP of pancreatic origin, and CRS and HIPEC were performed. Intraoperatively, the pancreatic tumor was perforated, and there was a large amount of mucinous ascites. We performed distal pancreatectomy in addition to CRS and HIPEC, with no intraoperative complications. The postoperative course was uneventful, and the patient survived after 6 months without recurrence. CRS with HIPEC may be a feasible treatment option for PMP of pancreatic origin.

Actual 5-Year Survival After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Carcinomatosis of Colorectal Origin.

BACKGROUND: Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) improves survival compared with chemotherapy alone in patients with peritoneal carcinomatosis (PC) of colorectal (CRC) origin, however, long-term survival data are lacking. We report the actual survival of patients who underwent CRS/HIPEC for PC of CRC origin with a minimum potential 5-year follow-up period to identify factors that preclude long-term survival. METHODS: We performed a retrospective analysis of a prospective database, analyzing patients undergoing CRS/HIPEC for PC of CRC origin from 2007 to 2017. Patients with aborted CRS/HIPEC, postoperative follow-up <90 days, or non-CRC histology were excluded. Overall survival (OS) and disease-free survival (DFS) were measured from date of surgery. Surviving patients with <60 months of follow-up were censored at date of last follow-up. RESULTS: A total of 103 patients met inclusion criteria and were analyzed. CC score 0-1 was achieved in 89.3% of patients, and median peritoneal cancer index (PCI) was 9 (interquartile range [IQR] 5-17). Ninety-day mortality was 2.9%. The median follow-up of survivors was 88 months. Five-year OS was 36%, and median OS was 42.5 months. Factors independently associated with poor survival included high PCI (PCI = 14-20, hazard ratio [HR] 3.1, p = 0.007, and PCI > 20, HR 5.3, p ≤ 0.001) and incomplete CRS (CC score-2, HR 2.96, p = 0.02). Patients with low PCI (0-6) had 5-year OS 60.7%. CONCLUSIONS: Actual 5-year OS was 36% and median OS was 42.5 months. Our study demonstrates that patients with PC from CRC origin with low PCI who undergo complete surgical resection can achieve favorable long-term survival.

Quality-of-Life Outcomes for Patients Taking Opioids and Psychotropic Medications Before Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) on quality of life (QoL) for patients taking opioids and psychotropic medications preoperatively is unclear. METHODS: This study retrospectively reviewed a CRS-HIPEC single-center prospectively maintained database for 2012-2016. Demographics and clinical data on opioids/psychotropic medication use were collected via chart review. The study collected QoL outcomes at baseline, then 3, 6, and 12 months postoperatively via the Center for Epidemiologic Studies Depression Scale (CES-D), Brief Pain Inventory, Functional Assessment of Cancer Therapy, and 36-Item Short-Form Health Survey. Differences in QoL between the groups were calculated using repeated measures analysis of variance regression. Descriptive statistics and Kaplan-Meier analyses were performed. RESULTS: Of 388 patients, 44.8% were taking opioids/psychotropic medications preoperatively. At baseline, those taking opioids/psychotropic medications preoperatively versus those not taking these medications had significantly worse QoL. By 1 year postoperatively, the QoL measures did not differ significantly except for emotional functioning (e.g., no medications vs. opioids/psychotropic medications: CES-D, 5.6 vs. 10.1). Median survival did not differ significantly (opioids/psychotropic medications vs. no medications: 52.3 vs. 60.6 months; p = 0.66). At 1 year after surgery, a greater percentage of patients were taking opioids, psychotropic medications, or both than at baseline (63.2% vs. 44.8%; p < 0.001). CONCLUSION: Despite worse baseline QoL, patients who took opioids/psychotropic medications had QoL scores 1 year postoperatively similar to the scores of those who did not except in the emotional domains. These data point to the potential utility of a timed psychosocial intervention to enhance emotional adaptation and further support the role of CRS-HIPEC in improving QoL.

Progress in the treatment of malignant ascites.

Malignant ascites occurs as a symptom of the terminal stage of cancer, affecting the quality of life through abdominal distension, pain, nausea, anorexia, dyspnea and other symptoms. We describe the current main drug treatments in addition to surgery according to the traditional and new strategies. Traditional treatments were based on anti-tumor chemotherapy and traditional Chinese medicine treatments, as well as diuretics to relieve the patient's symptoms. New treatments mainly involve photothermal therapy, intestinal therapy and targeted immunity. This study emphasizes that both traditional and new therapies have certain advantages and disadvantages, and medication should be adjusted according to different periods of use and different patients. In conclusion, this article reviews the literature to systematically describe the primary treatment modalities for malignant ascites.

International Expert Consensus on Defining Textbook Oncologic Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastasis.

BACKGROUND: Textbook oncologic outcome (TOO) is a composite metric shown to correlate with improved survival after curative intent oncologic procedures. Despite increasing use among disciplines in surgical oncology, no consensus exists for its definition in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). STUDY DESIGN: An international consensus-based study employed a Delphi methodology to achieve agreement. Fifty-four senior surgeons from the peritoneal surface malignancies field received a questionnaire comprising TOO parameters divided into 3 surgical domains: operative, short-term, and long-term postoperative outcomes. Two online meetings with participants defined the new criteria. Consensus was achieved when 75% of agreement rate was reached. Clinical data of patients who underwent CRS and HIPEC for colorectal peritoneal metastasis between 2010 and 2022 from 1 designated center (Sheba Medical Center) were collected, the consensus definition applied and outcomes analyzed. RESULTS: Thirty-eight surgeons (70%) participated. Expert consensus TOO parameters for colorectal peritoneal metastasis CRS and HIPEC included the absence of unplanned reoperations during 30 days postoperation, absence of severe postoperative complications (Clavien-Dindo ≥III), absence of unplanned readmissions during 30 days postoperation, 90-day postoperative mortality, and absence of contraindications for chemotherapy within 12 weeks from operation, and included the achievement of complete cytoreduction (CC0). The study cohort consisted of 251 patients, and 151 (60%) met TOO criteria. Patients who achieved TOO had significantly better overall survival (median 67.5 months, 95% CI) vs patients who did not achieve TOO (median 44.6 months, 95% CI, p < 0.001) and significantly improved disease-free survival (median, 12 months, 95% CI, vs 9 months, 95% CI, p = 0.01). CONCLUSIONS: Achievement of TOO as defined by consensus statement is associated with improved survival.

Low-Grade Pseudomyxoma Peritonei Behaving as a High-Grade Disease: A Case Series and Literature Review.

Patients with low-grade appendiceal mucinous carcinomas (LAMNs) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have a favorable prognosis. However, a subgroup of patients presents a clinically aggressive course with disease progression despite receiving treatment. The purpose of this study is to report the experience of clinically aggressive LAMN patients treated by the same team, and to present a review of the literature. The cases of four patients with clinically aggressive LAMNs were reviewed. Clinical and histopathological characteristics were re-examined. Recurrences and the time of recurrence, as well as the survival time, were recorded. These patients were four men with clinically aggressive LAMNs treated with CRS plus HIPEC. One of them underwent CC-0 surgery, two underwent CC-1 surgery, and one underwent CC-3 surgery. All patients received systemic chemotherapy after surgery. Recurrence was recorded in three of the patients within 4-23 months after the initial treatment. Two of the patients underwent secondary CRS. Three patients died of disease recurrence within 13-23 months, and one is alive with a disease relapse at 49 months after his initial surgery. LAMNs were identified in both the initial specimens and the specimens obtained during reoperation. The prognosis of LAMN patients treated with CRS plus HIPEC is favorable. A small number of patients present a clinically aggressive course that is unresponsive to any treatment. Molecular and genetic studies are required to identify this group of LAMN patients who have an unfavorable prognosis.

Impact of Successful Implementation of an Enhanced Recovery After Surgery Protocol for Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are complex operations for the treatment of peritoneal metastases. Enhanced recovery after surgery (ERAS) protocols are intended to standardize preoperative, intraoperative, and postoperative pathways, with the goal of improving patient care. This study describes feasibility and outcomes after implementing an ERAS protocol for CRS/HIPEC at a tertiary academic center. METHODS: A single-institution experience of CRS/HIPEC was reviewed from January 2020 to March 2023. Patients were categorized according to whether they underwent CRS/HIPEC before or after ERAS initiation. Outcomes and protocol adherence were evaluated. RESULTS: A total of 115 CRS/HIPEC operations were included-74 before and 41 after ERAS implementation. Median age was younger in the post-ERAS group, whereas sex, comorbidities, peritoneal carcinomatosis index, operation performed, and operative time were similar between groups. The most common primary cancer sites were gynecologic (40%), appendiceal (24%), and colorectal (22%). Adherence to all postoperative ERAS components was 76%. More post-ERAS patients ambulated by postoperative day (POD) 1 (90% vs. 54%; p < 0.001), tolerated liquid diet by POD 2 (88% vs. 32%; p < 0.001), and had foley removed by POD 3 (86% vs. 43%; p < 0.001). There was a trend toward decreased length of stay in the post-ERAS cohort (7 vs. 8 days; p = 0.092), with no difference in major complications, intensive care unit admission, or 30-day readmission. CONCLUSIONS: Despite the heterogeneity of CRS/HIPEC operations, implementing an ERAS protocol for our patients was feasible and resulted in postoperative outcomes and adherence comparable with that of other major abdominal surgeries. This supports the potential for success in ERAS programs for CRS/HIPEC patients.