Small bowel involvement is a prognostic factor in colorectal carcinomatosis treated with complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy

<p>Abstract</p> <p>Background</p> <p>Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment for patients with peritoneal carcinomatosis (PC). Our objective was to identify new prognostic factors in patients with PC from colorectal cancer treated with this procedure.</p> <p>Methods</p> <p>All patients with PC from colorectal cancer treated by HIPEC from January 2000 to December 2007 were prospectively included. The tumor extension was assessed by the Peritoneal Cancer Index (PCI) and the residual disease was recorded using the completeness cytoreductive score (CCs). All clinical and treatment data were computed in univariate and multivariable analyses using survival as primary end point.</p> <p>Results</p> <p>We carried out 51 complete procedures in 49 consecutive patients. The mean PCI was 10. The allocation of CCs was: CC-0 = 37, CC-1 = 14. The five-year overall and progression-free survival rate were 40% and 20%, respectively. Several prognostic factors for survival were identified by univariate analysis: PCI < 9 (<it>P </it>< 0.001), CC-0 vs. CC-1 (<it>P </it>< 0.01) and involvement of area 4 (<it>P </it>= 0.06), area 5 (<it>P </it>= 0.031), area 7 (<it>P </it>= 0.014), area 8 (<it>P </it>= 0.022), area 10 (<it>P </it>< 0.0001), and area 11 (<it>P </it>= 0.02). Only the involvement of the distal jejunum (area 10) was significant in the multivariable analysis (<it>P </it>= 0.027).</p> <p>Conclusions</p> <p>We demonstrated that the involvement of area 10 (distal jejunum of the PCI score) was an independent factor associated with poor prognosis.</p

La chimiohyperthermie intrapéritonéale (CHIP) dans les cancers ovariens

RésuméLe cancer de l’ovaire reste, en France, la quatrième cause de décès par cancer chez la femme. Il s’agit d’une maladie souvent diagnostiquée à un stade évolué avec carcinose péritonéale (CP) et dont l’histoire naturelle est marquée par des récidives essentiellement péritonéales et l’acquisition d’un profil de chimiorésistance. Malgré les nombreuses lignes de chimiothérapie systémique et les chirurgies de cytoréduction (CCR), le pronostic de ces récidives reste sombre. Depuis plus de 20ans, plusieurs équipes spécialisées ont développé un traitement combiné des CP, associant une chirurgie de cytoréduction complète à une chimiohyperthermie intrapéritonéale (CHIP). Cette thérapeutique a une large place dans le traitement des CP d’origine non gynécologiques. Le rationnel pour une utilisation de la CHIP dans le traitement des CP d’origine ovarienne est important. D’une part, 3 études prospectives randomisées ont démontré la supériorité de l’utilisation de la chimiothérapie intrapéritonéale (sans hyperthermie) par rapport à la chimiothérapie systémique sur des patientes sélectionnées. D’autre part, des études rétrospectives et cas-témoins évaluant la CHIP font état de données de survie encourageantes, en particulier en cas de récidive chimiorésistante. Néanmoins, la morbidité et la mortalité associées doivent appeler à une sélection rigoureuse des patientes éligibles, et à une prise en charge multidisciplinaire dans des centres spécialisés. L’évaluation de la CHIP doit se faire par le moyen d’études randomisées à différents stades évolutifs : 1re ligne, consolidation, récidives qu’elles soient chimiorésistantes ou chimiosensibles. Plusieurs études européennes sont en cours.SummaryOvarian cancer remains the fourth leading cause of cancer death in women in France. It is all too often diagnosed at an advanced stage with peritoneal carcinomatosis (PC), but remains confined to the peritoneal cavity throughout much of its natural history. Because of cellular selection pressure over time, most tumor recurrences eventually develop resistance to systemic platinum. Options for salvage therapy include alternative systemic chemotherapies and further cytoreductive surgery (CRS), but the prognosis remains poor. Over the past two decades, a new therapeutic approach to PC has been developed that combines CRS with hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment strategy has already been shown to be effective in non-gynecologic carcinomatosis in numerous reports. There is a strong rationale for the use of HIPEC for PC of ovarian origin. On the one hand, three prospective randomized trials have demonstrated the superiority of intraperitoneal chemotherapy (without hyperthermia) in selected patients compared to systemic chemotherapy. Moreover, retrospective studies and case-control studies of HIPEC have reported encouraging survival data, especially when used to treat chemoresistant recurrence. However, HIPEC has specific morbidity and mortality; this calls for very careful selection of eligible patients by a multidisciplinary team in specialized centers. HIPEC needs to be evaluated by means of randomized trials for ovarian cancer at different developmental stages: as first line therapy, as consolidation, and for chemoresistant recurrence. Several European Phase III studies are currently ongoing

The Delphi and GRADE methodology used in the PSOGI 2018 consensus statement on Pseudomyxoma Peritonei and Peritoneal Mesothelioma

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%–100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future

Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications.

Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12-15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62-88% was reported for patients with ovarian cancer (median survival of 11-14 months), 50-91% for gastric cancer (median survival of 8-15 months), 71-86% for colorectal cancer (median survival of 16 months), and 67-75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies

Primary and metastatic peritoneal surface malignancies

Peritoneal surface malignancies comprise a heterogeneous group of primary tumours, including peritoneal mesothelioma, and peritoneal metastases of other tumours, including ovarian, gastric, colorectal, appendicular or pancreatic cancers. The pathophysiology of peritoneal malignancy is complex and not fully understood. The two main hypotheses are the transformation of mesothelial cells (peritoneal primary tumour) and shedding of cells from a primary tumour with implantation of cells in the peritoneal cavity (peritoneal metastasis). Diagnosis is challenging and often requires modern imaging and interventional techniques, including surgical exploration. In the past decade, new treatments and multimodal strategies helped to improve patient survival and quality of life and the premise that peritoneal malignancies are fatal diseases has been dismissed as management strategies, including complete cytoreductive surgery embedded in perioperative systemic chemotherapy, can provide cure in selected patients. Furthermore, intraperitoneal chemotherapy has become an important part of combination treatments. Improving locoregional treatment delivery to enhance penetration to tumour nodules and reduce systemic uptake is one of the most active research areas. The current main challenges involve not only offering the best treatment option and developing intraperitoneal therapies that are equivalent to current systemic therapies but also defining the optimal treatment sequence according to primary tumour, disease extent and patient preferences. New imaging modalities, less invasive surgery, nanomedicines and targeted therapies are the basis for a new era of intraperitoneal therapy and are beginning to show encouraging outcomes

Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy

BACKGROUND: Peritoneal carcinomatosis (PC) from gastric cancer has long been regarded a terminal disease with a short median survival. New locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved and suggest improved survival. MATERIALS AND METHODS: A retrospective multicentric study was performed in French-speaking centers to evaluate the toxicity and the principal prognostic factors in order to identify the best indications. All patients had cytoreductive surgery and PIC: hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC). RESULTS: The study included 159 patients from 15 institutions between February 1989 and August 2007. The median follow-up was 20.4 months. HIPEC was the PIC used for 150 procedures. Postoperative mortality and grade 3-4 morbidity rates were 6.5 and 27.8%, respectively. By multivariate analysis, the institution had a significant influence on toxicity. The overall median survival was 9.2 months and 1-, 3-, and 5-year survival rates were 43, 18, and 13%, respectively. The only independent prognostic indicator by multivariate analysis was the completeness of cytoreductive surgery. For patients treated by complete cytoreductive surgery, the median survival was 15 months with a 1-, 3-, and 5-year survival rate of 61, 30, and 23%, respectively. CONCLUSIONS: The therapeutic approach combining cytoreductive surgery with PIC for patients with gastric carcinomatosis may achieve long-term survival in a selected group of patients (limited and resectable PC). The high mortality rate underlines this necessarily strict selection that should be reserved to experienced institutions involved in the management of PC and gastric surgery