Hyperthermic Intraperitoneal Chemotherapy For Pseudomyxoma Peritonei Research Articles

Long‐term outcomes and survival analysis of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei at a newly established peritoneal malignancy centre in Japan

AbstractBackgroundCytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is established in the management of pseudomyxoma peritonei (PMP), selected cases of peritoneal mesothelioma, and resectable colorectal or ovarian peritoneal metastases in Western countries. However, the efficacy and feasibility of these techniques are not well established in the Asian population, and little has been reported on long‐term survival outcomes for surgically resected PMP patients.Materials and MethodsRetrospective analysis of a prospective database of short‐ and longer‐term outcomes of consecutive patients who underwent CRS and HIPEC for PMP in a newly established peritoneal malignancy unit in Japan between 2010 and 2016.ResultsA total of 105 patients underwent CRS and HIPEC and 57 maximal tumor debulking (MTD) for pseudomyxoma peritonei. In the CRS group, the primary tumor was appendiceal in 94 patients (90%) followed by ovarian and colorectal. Major postoperative complications occurred in 22/105 patients (21%) with one in‐hospital mortality (0.9%). The 5‐year overall and disease‐free survival rates for the CRS group were 74.2% and 50.1%, respectively. Multivariate analysis revealed unfavorable histology to be the significant predictor of reduced overall and disease‐free survival. Completeness of cytoreduction, CA19‐9, and CA125 were also associated with disease‐free survival.ConclusionsThis is the first report on long‐term outcomes and survival analysis of CRS and HIPEC for PMP in the Asian population. CRS and HIPEC can be conducted with reasonable safety and favorable survival in a new center. Complete tumor removal and histological type are the strongest prognostic factors for both overall and disease‐free survival.

Recurrence after cytoreductive surgery and HIPEC for pseudomyxoma peritonei: A single-center retrospective cohort study.

Pseudomyxoma peritonei (PMP) is a rare disease characterized by progressive build-up of mucinous deposits inside the abdominal cavity. The aim of this study was to investigate the effect of disease recurrence on overall survival in patients with PMP after cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). One-hundred thirty-two consecutive PMP patients treated with CRS + HIPEC at Helsinki University Hospital between 2008 and 2017 were included. The impact of clinicopathological and treatment-related characteristics on recurrence and overall survival was evaluated. The median follow-up time in the study was 5.04 (range = 0.05-11.60) years. In 121 (91.7%) patients, the disease was classified as low grade and 11 (8.3%) had high-grade disease. In the low-grade group, 26 (21.5%) patients developed a recurrence during follow-up compared to 6 (54.5%) patients in the high-grade group. In the low-grade group, cumulative survival was 98.2%, 91.4%, and 91.4% at 3, 6, and 8 years, respectively. In the high-grade group, cumulative survival was 90.0% and 78.8% at 3 and 6 years, respectively. In patients with recurrent disease, the cumulative survival was 100%, 84.6%, and 84.6% at 3, 6, and 8 years in the low-grade category and 80.0% and 60.0% at 3 and 6 years in the high-grade category, respectively. In the low-grade group, a statistically significant correlation with recurrence but not with overall survival was identified with peritoneal cancer index (PCI), carcinoembryonic antigen (CEA), and the number of affected regions. The recurrence of low-grade PMP does not significantly affect overall survival of patients. Disease extent may not be a prognostic indicator after curative CRS and HIPEC in low-grade PMP.

Overall Survival is More Closely Associated with Peritoneal than Primary Appendiceal Pathological Grade in Pseudomyxoma Peritonei with Discordant Pathology.

The WHO classification of mucinous appendix neoplasms and pseudomyxoma peritonei (PMP) describes low- and high-grade histology and is of prognostic importance. The metastatic peritoneal disease grade can occasionally be different from the primary appendix tumor. This analysis aimed to report outcomes from a high-volume center in patients with pathological discordance. This was a retrospective analysis of prospective data of patients treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for PMP at a single institution between January 2016 and December 2020. Reporting was by pathologists with a special interest in peritoneal malignancy. Discordant pathology was classified as a low-grade primary appendix tumor with high-grade peritoneal disease, or a high-grade primary appendix tumor with low-grade peritoneal disease. Outcomes analyzed were overall and recurrence-free survival, and Kaplan-Meier survival curves and the log-rank test were used to analyze the outcomes. Between 2016 and 2020, 830 patients underwent CRS and HIPEC for PMP, of whom 37 (4.4%) had discordant pathology. The primary appendix tumors were low-grade in 23 patients and high-grade in 14 patients. The median Peritoneal Cancer Index (PCI) was significantly higher in patients with a low-grade primary tumor (31 vs. 16; p=0.001), while complete cytoreduction (CC0/1) was achieved in 31/37 (83.8%) patients. The median follow-up was 19 months. Overall survival was worse in those with high-grade peritoneal disease (p=0.029), whereas recurrence-free survival was similar in both groups (p=0.075). In PMP with pathological discordance, the peritoneal disease grade influences prognosis and survival.

Survival after complete cytoreductive surgery and HIPEC for extensive pseudomyxoma peritonei

IntroductionThe optimal treatment for pseudomyxoma peritonei (PMP) combines complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Yet, achieving CRS is challenging in the case of extensive involvement of the peritoneal cavity and the survival benefit in this setting remains uncertain. The present study evaluated the surgical outcomes according to the peritoneal extent. MethodsBetween 1992 and 2014, 245 patients underwent CRS and HIPEC for PMP in our institution. Their characteristics were reviewed using a prospective database. Extensive PMP was defined as a peritoneal cancer index (PCI) ≥ 28. Sixty-one patients with extensive PMP were compared to 184 with non-extensive PMP. ResultsSevere complications were more frequent in the extensive group (46% vs. 23%, p < 0.001) but the post-operative mortality was not significantly different (8% vs. 3%, p = 0.1). The 5-year disease-free survival reached 45% in the extensive and 78% in the non-extensive group (p < 0.0001). The 5-year overall survival was 70% and 90% in the extensive and non-extensive group respectively (p < 0.021). ConclusionCRS with HIPEC offers prolonged survival even in the case of extensive PMP. Because of the high rate of surgical morbidity in the extensive group, patients should be carefully selected.

Impact of ovarian metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancy originating from appendiceal and colorectal cancer.

Ovarian metastases from gastrointestinal tract malignancies have been considered an ominous finding with poor prognosis. The aim of this project was to determine the impact on survival, and potential cure, when cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are combined to treat peritoneal malignancy in women with Krukenberg tumours. A retrospective analysis of prospectively collected data between January 2010 and July 2015. Female patients undergoing complete CRS (macroscopic tumour removal) and HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin, or colorectal peritoneal metastases (CPM) were included. Survival was estimated using the Kaplan-Meier method and survival rates compared using the log-rank test. In total, 889 patients underwent surgery for peritoneal malignancy, of whom 551 were female. Of these, 504/551 (91%) underwent complete CRS and HIPEC. Overall, 405/504 (80%) had at least one involved ovary removed either during CRS and HIPEC or at their index prereferral operation. Three hundred and fifty-two patients (87%) had an appendiceal tumour and 53 (13%) had CPM. At a median follow up of 40months, overall survival (OS) did not differ significantly between patients with or without ovarian involvement in women with a primary low-grade appendiceal tumour or CPM. In women with high-grade primary appendiceal pathology, OS was significantly lower in patients with ovarian metastases compared with those without ovarian involvement. Women with ovarian metastases from low-grade appendiceal tumours or colorectal cancer treated with CRS and HIPEC have similar survival rates to patients without ovarian metastases. Long-term survival and cure is feasible in patients amenable to complete tumour removal.

CRS and HIPEC for PMP-Use of the LC-CUSUM to Determine the Number of Procedures Required to Attain a Minimal Level of Proficiency in Delivering the Combined Modality Treatment.

The learning curve for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) which peaks at 90 procedures for the surgeon may take several years to reach. The cumulative summation (CUSUM) test of the learning curve (LC-CUSUM) was used to assess the safety of the procedure (minimal level of proficiency for the surgeon) in terms of morbidity, mortality, and completeness of cytoreduction and early oncological failure before the peak of the learning curve had been reached. The limits for h0 and h1 were set based on the results of large series of such cases published before. From 2011 to 2016, 77 patients with PMP underwent CRS and HIPEC. The mean peritoneal cancer index (PCI) was 28 and 75% of the patients had a CC-0/1 resection. The grade 3-4 morbidity was 42.6% and the mortality was 5.2%. The 5-year overall survival (OS) was 62.3% and the 3-year disease-free survival (DFS) was 71%. The LC-CUSUM analysis showed that for in-hospital mortality, acceptable limits are reached after the 57th case, after the 38th case for the grade 3-4 morbidity and CC-2/3 resections both and after the 70th case for early oncological failure. The number of cases required to attain a minimal level of proficiency for each prognostic variable is different. Using the CUSUM test, surgeons can analyze their performance and determine the areas in which they need to improve before the peak of the learning curve is reached. These outcomes reflect the performance of the multidisciplinary team and not the surgeon alone.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei and appendix tumours in elderly patients: Is it justified?

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei and appendix tumours are widespread in the world. It is unclear what should be the attitude in elderly patients. This retrospective multicenter study collected the database from ten Spanish centers from Spanish Group of Peritoneal Cancer Surgery. The study period was between November 2002 and March 2014. Seventeen patients with age greater than or equal to 75years with peritoneal carcinomatosis from pseudomyxoma peritonei and appendix tumours met the selection criteria for the study. Outcomes in terms of morbidity and mortality such as disease-free and overall survival were analyzed. Median PCI was 16 (range 6-39). Ten postoperative adverse events were detected in nine patients (44.4%). 28% were grade I-II and 17% were grade III-IV. Disease-free survival at 1 and 3years was 67 and 44%, respectively. Overall survival at 1 and 3years was 100 and 88%, respectively. Only cytoreduction was related to worst disease free survival after univariate (p=0.007) and multivariate (OR 11.639, 95% CI 1.24-109.74, p=0.03) analyses. Cytoreduction was related to the worst overall survival after univariate analysis (p=0.046). Cytoreductive surgery and HIPEC for pseudomyxoma peritonei and appendix tumours in elderly patients it is a procedure with feasible postoperative morbi-mortality and survival outcomes. researchregistry1587 (retrospectively registered).

Long-term survival after aggressive treatment of relapsed serosal or distant pseudomyxoma peritonei

IntroductionComplete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have dramatically changed the prognosis of patients with pseudomyxoma peritonei (PMP). However, recurrences can still occur and no consensus has been reached regarding their optimal treatments. This study aimed to analyze the patterns of recurrence after CCRS plus HIPEC for PMP and potential subsequent treatments of these lesions. Patients and methodsBetween 1992 and 2014, patients who had relapsed after treatment of PMP were selected from a prospective database of 251 patients who had undergone CCRS plus HIPEC with a curative intent. ResultsAfter a median follow-up of 85 months, 66 patients (26%) had relapsed with a median free interval of 25 months. The first recurrence was mostly located in the peritoneum, isolated in 50 patients (76%) and associated with extraperitoneal disease in 6 patients. Curatively intended treatment of the relapse, combining surgery and chemotherapy was achievable in 76% of the patients, leading to a 5-year overall survival (OS) rate of 83% from the date of treatment of the first recurrence. In contrast, the 5-year OS rate was only 27% (p < 0.001) for patients treated with non-curative therapy. An isolated peritoneal recurrence was predictive of greater amenability to curative therapy and a better prognosis. ConclusionAfter CCRS plus HIPEC, serosal recurrences were more common than their distant counterparts. Distant relapses' emergence has raised the question of their optimal treatments. Very long-term survival can be obtained after further treatment of recurrent PMP for patients with limited disease and good general status.

Morbidity and Mortality With Cytoreductive Surgery and Intraperitoneal Chemotherapy

Evidence for the efficacy of cytoreductive surgery, combined with hyperthermic intraperitoneal chemotherapy (HIPEC), in the treatment of peritoneal carcinomatosis is accumulating. Many centers around the world now have considerable experience of the complex techniques required to achieve complete cytoreduction with the administration of HIPEC. Procedure-related morbidity ranges from 12% to 67.6% and mortality from 0% to 9% in recent studies of cytoreductive surgery and HIPEC for pseudomyxoma peritonei. A number of specialized centers have studied the factors that influence perioperative complications and mortality and have demonstrated impressive reductions in morbidity and mortality over time. However, for this treatment to be accepted as standard of care, teams undertaking this treatment strategy must aim to minimize morbidity and mortality by learning from the experience of established centers and using the "global learning curve."