2022 Peritoneal Surface Oncology Group International Consensus on HIPEC Regimens for Peritoneal Malignancies: Colorectal Cancer.

BACKGROUND: Selected patients with peritoneal metastases of colorectal cancer (PM-CRC) can benefit from potentially curative cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC), with a median overall survival (OS) of more than 40 months. OBJECTIVE: The aims of this evidence-based consensus were to define the indications for HIPEC, to select the preferred HIPEC regimens, and to define research priorities regarding the use of HIPEC for PM-CRC. METHODS: The consensus steering committee elaborated and formulated pertinent clinical questions according to the PICO (patient, intervention, comparator, outcome) method and assessed the evidence according to the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. Standardized evidence tables were presented to an international expert panel to reach a consensus (4-point, weak and strong positive/negative) on HIPEC regimens and research priorities through a two-round Delphi process. The consensus was defined as ≥ 50% agreement for the 4-point consensus grading or ≥ 70% for either of the two combinations. RESULTS: Evidence was weak or very weak for 9/10 clinical questions. In total, 70/90 eligible panelists replied to both Delphi rounds (78%), with a consensus for 10/10 questions on HIPEC regimens. There was strong negative consensus concerning the short duration, high-dose oxaliplatin (OX) protocol (55.7%), and a weak positive vote (53.8-64.3%) in favor of mitomycin-C (MMC)-based HIPEC (preferred choice: Dutch protocol: 35 mg/m2, 90 min, three fractions), both for primary cytoreduction and recurrence. Determining the role of HIPEC after CRS was considered the most important research question, regarded as essential by 85.7% of the panelists. Furthermore, over 90% of experts suggest performing HIPEC after primary and secondary CRS for recurrence > 1 year after the index surgery. CONCLUSIONS: Based on the available evidence, despite the negative results of PRODIGE 7, HIPEC could be conditionally recommended to patients with PM-CRC after CRS. While more preclinical and clinical data are eagerly awaited to harmonize the procedure further, the MMC-based Dutch protocol remains the preferred regimen after primary and secondary CRS.

[Intraperitoneal therapy for carcinomatosis in ovarian cancer: proposed treatment algorithm]. / Traitements intrapéritonéaux de la carcinose ovarienne : proposition d'algorithmes décisionnels.

Ovarian cancer is the first cause of death by gynecological cancer. Most of the patients are diagnosed with peritoneal carcinomatosis that represents a therapeutic challenge. Its management implies maximal cytoreductive surgery with survival benefit. Over the last three decades, several strategies of intra-peritoneal chemotherapy have been investigated. This includes intra-peritoneal adjuvant chemotherapy that is used mainly in North America, hyperthermic intraperitoneal chemotherapy (HIPEC) and more recently pressurized intraperitoneal aerosol chemotherapy (PIPAC). In the current article, we review the evidence in favor of each therapeutic approach, and we propose treatment algorithms depending on the clinical situation of ovarian cancer patients: upfront, platinum-sensitive and platinum-resistant relapse.

Le cancer de l'ovaire est la première cause de décès par cancer gynécologique. La plupart des patientes sont diagnostiquées au stade de carcinose péritonéale qui représente un défi thérapeutique. Sa prise en charge chirurgicale implique une cytoréduction maximaliste. Au cours des 30 dernières années, plusieurs stratégies de chimiothérapie intrapéritonéale ont été testées afin d'améliorer le contrôle de la carcinose péritonéale. Il s'agit des chimiothérapies intrapéritonéale adjuvante utilisée surtout en Amérique du Nord, hyperthermique intrapéritonéale (CHIP) et intrapéritonéale pressurisée en aérosols (PIPAC). Dans cet article, nous reprenons les données de la littérature sur chacune de ces trois approches thérapeutiques et proposons des algorithmes décisionnels selon la situation clinique des patientes traitées pour un cancer de l'ovaire : au diagnostic, récidive platine-sensible et platine-résistante.

ESPEN practical guideline: Clinical nutrition in surgery.

Early oral feeding is the preferred mode of nutrition for surgical patients. Avoidance of any nutritional therapy bears the risk of underfeeding during the postoperative course after major surgery. Considering that malnutrition and underfeeding are risk factors for postoperative complications, early enteral feeding is especially relevant for any surgical patient at nutritional risk, especially for those undergoing upper gastrointestinal surgery. The focus of this guideline is to cover both nutritional aspects of the Enhanced Recovery After Surgery (ERAS) concept and the special nutritional needs of patients undergoing major surgery, e.g. for cancer, and of those developing severe complications despite best perioperative care. From a metabolic and nutritional point of view, the key aspects of perioperative care include the integration of nutrition into the overall management of the patient, avoidance of long periods of preoperative fasting, re-establishment of oral feeding as early as possible after surgery, the start of nutritional therapy immediately if a nutritional risk becomes apparent, metabolic control e.g. of blood glucose, reduction of factors which exacerbate stress-related catabolism or impaired gastrointestinal function, minimized time on paralytic agents for ventilator management in the postoperative period, and early mobilization to facilitate protein synthesis and muscle function.

HIPEC Methodology and Regimens: The Need for an Expert Consensus.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is performed with a wide variation in methodology, drugs, and other elements vital to the procedure. Adoption of a limited number of regimens could increase the collective experience of peritoneal oncologists, make comparison between studies more meaningful, and lead to a greater acceptance of results from randomized trials. This study aimed to determine the possibility of standardizing HIPEC methodology and regimens and to identify the best method of performing such a standardization. METHODS: A critical review of preclinical and clinical studies evaluating the pharmacokinetic aspects of different HIPEC drugs and drug regimens, the impact of hyperthermia, and the efficacy of various HIPEC regimens as well as studies comparing different regimens was performed. RESULTS: The preclinical and clinical data were limited, and studies comparing different regimens were scarce. Many of the regimens were neither supported by preclinical rationale or data nor validated by a dose-escalating formal phase 1 trial. All the regimens were based on pharmacokinetic data and did not take chemosensitivity of peritoneal metastases into account. Personalized medicine approaches such as patient-derived tumor organoids could offer a solution to this problem, although clinical validation is likely to be challenging. CONCLUSIONS: Apart from randomized trials, more translational research and phases 1 and 2 studies are needed. While waiting for better preclinical and clinical evidence, the best way to minimize heterogeneity is by an expert consensus that aims to identify and define a limited number of regimens for each indication and primary site. The choice of regimen then can be tailored to the patient profile and its expected toxicity and the methodology according regional factors.

Site of Recurrence and Survival After Surgery for Colorectal Peritoneal Metastasis.

BACKGROUND: Multimodal treatment, including systemic treatment and surgery, improved the prognosis of peritoneal metastasis (PM). Despite all efforts, recurrence rates remain high, and little data are available about clinical behavior or molecular patterns of PM in comparison to hematogenous metastasis. Here, we aimed to analyze recurrence patterns after multimodal treatment for PM from colorectal cancer. METHODS: Patients with colorectal PM undergoing multimodal treatment including systemic chemotherapy and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 2005 and 2017 at 4 centers were analyzed retrospectively. RESULTS: A total of 505 patients undergoing CRS/HIPEC were analyzed. Of the patients, 82.1% received preoperative chemotherapy. Median peritoneal cancer index was 6 (interquartile range = 3-11). Median disease-free and overall survival was 12 (95% confidence interval [CI] = 11 to 14) months and 51 (95% CI = 43 to 62) months, respectively. Disease recurred in 361 (71.5%) patients, presenting as isolated peritoneal recurrence in 24.6%, isolated hematogenous recurrence in 28.3%, and mixed recurrence in 13.9% of patients. Recurrence to the peritoneum was associated with an impaired time from recurrence to death of 21 (95% CI = 18 to 31) months for isolated peritoneal and 22 (95% CI = 16 to 30) months for mixed recurrence, compared with 43 (95% CI = 31 to >121) months for hematogenous recurrence (hazard ratio [HR] = 1.79, 95% CI = 1.27 to 2.53; P = .001; and HR = 2.44, 95% CI = 1.61 to 3.79; P < .001). On multiple logistic regression analysis, RAS mutational status (odds ratio [OR] = 2.42, 95% CI = 1.11 to 5.47; P = .03) and positive nodal stage of the primary (OR = 3.88, 95% CI = 1.40 to 11.86; P = .01) were identified as predictive factors for peritoneal recurrence. CONCLUSIONS: This study highlights the heterogeneity of peritoneal metastasis in patients with colorectal cancer. Recurrent peritoneal metastasis after radical treatment represents a more aggressive subset of metastatic colorectal cancer.

Diagnostic Nodes of Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Among Colorectal Cancer Patients: A Swiss National Multicenter Survey.

BACKGROUND: The management of patients with colorectal cancer (CRC) with peritoneal metastases is challenging, and the roles of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are unclear and debated among experts. MATERIALS AND METHODS: The experts of the Swiss Peritoneal Cancer Group were contacted and agreed to participate in this analysis. Experts from 9 centers in Switzerland provided their decision algorithms for CRS/HIPEC for patients with or at high risk for peritoneal metastases from CRC. Their responses were converted into decision trees on the basis of objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies. RESULTS: The final treatment algorithms included a total of 5 decision criteria (age, Peritoneal Cancer Index [PCI], extraperitoneal metastases, Peritoneal Surface Disease Severity Score, and various risk factors [RF]) and 2 treatment options (HIPEC, yes or no). HIPEC was never recommended for patients without peritoneal metastases in the absence of RF for peritoneal metastases. For patients with a PCI ≤15 without organ metastases, all centers recommended CRS/HIPEC. There was also a consensus not to perform CRS/HIPEC in elderly patients (80 years and older), those with a PCI >20, and those with unresectable metastases. For patients with a PCI = 16 to 20, there was no consensus. CONCLUSION: Multiple decision criteria relevant to all participating centers were identified. Because patient selection for CRS/HIPEC remains difficult, uniform criteria for the term "high risk" for peritoneal metastases and systemic metastases are helpful. Future trials and guidelines should take these criteria into account.

Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin.

BACKGROUND: Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear. METHODS: Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses. A simple point-based risk score was developed to allow patient selection and outcome prediction. RESULTS: Data of 524 patients with a median age of 59 years and a median peritoneal cancer index of 7 (interquartile range: 3-12) were collected. A complete resection was possible in 505 patients; overall morbidity and 90-day mortality were 50.9% and 2.1%, respectively. PCI [hazard ratio (HR): 1.08], N1 stage (HR: 2.15), N2 stage (HR: 2.57), G3 stage (HR: 1.80) as well as KRAS (HR: 1.46) and BRAF (HR: 3.97) mutations were found to significantly impair survival after CRS/HIPEC on multivariate analyses. Mutations of RAS/RAF impaired survival independently of targeted treatment against EGFR. Consequently, a simple point-based risk score termed BIOSCOPE (BIOlogical Score of COlorectal PEritoneal metastasis) based on PCI, N-, G-, and RAS/RAF status was developed, which showed good discrimination [development area under the curve (AUC) = 0.72, validation AUC = 0.70], calibration (P = 0.401) and allowed categorization of patients into 4 groups with strongly divergent survival outcomes. CONCLUSION: RAS/RAF mutations impair survival after CRS/HIPEC. The novel BIOSCOPE score reflects tumor biology, adequately stratifies long-term outcomes, and improves patient assessment and selection.

[Sacral nerve stimulation, an effective treatment for fecal incontinence]. / La stimulation nerveuse sacrée, traitement efficace de l'incontinence fécale.

Sacral nerve stimulation (SNS) became recently an essential therapeutic modality in the treatment of anal incontinence. Indications range from anorectal functional disorders to limited sphincteric lesions. An electrode is inserted through a sacral foramen, generally S3, to stimulate the corresponding nerve root. Patient's selection needs a meticulous multidisciplinary approach. Improved continence of more than 50% is frequently encountered and quality of life is significantly improved after implantation. SNS is a minimal-invasive technique, with very few risks of complications.