The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: HIPEC Technologies.

This manuscript reports the results of an international consensus on technologies of hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) performed with the following goals: To provide recommendations for the technological parameters to perform HIPEC. To identify the role of heat and its application forms in treating peritoneal metastases. To provide recommendations regarding the correct dosimetry of intraperitoneal chemotherapy drugs and their carrier solutions. To identify for each intraperitoneal chemotherapy regimen the best dosimetry and fractionation. To identify areas of future research pertaining to HIPEC technology and regimens. This consensus was performed by the Delphi technique and comprised two rounds of voting. In total, 96 of 102 eligible panelists replied to both Delphi rounds (94.1%) with a consensus of 39/51 questions on HIPEC technical aspects. Among the recommendations that met with the strongest consensus were those concerning the dose of HIPEC drug established in mg/m2, a target temperature of at least 42°C, and the use of at least three temperature probes to pursue hyperthermia. Ninety minutes as the ideal HIPEC duration seemed to make consensus. These results should be considered when designing new clinical trials in patients with peritoneal surface malignancies.

Number of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Treatments is Associated with Longer Survival: Analysis of a Large Prospective Cohort of Patients With Unresectable Peritoneal Surface Malignancies.

OBJECTIVE: To analyze the reasons for stopping pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivered for unresectable peritoneal surface malignancies (PSM) and to determine survival in a large patient cohort of an experienced PIPAC center. BACKGROUND: PIPAC alone or combined with systemic chemotherapy was developed to palliatively treat unresectable PSM. Safety, tolerance and promising survival results were already reported, but the reasons for stopping treatment remain unclear and the influence of the number of PIPAC procedures on prognosis has not been evaluated. METHODS: A retrospective analysis of PIPAC procedures from a prospectively maintained single institution PSM database was conducted from January 2016 to January 2023. RESULTS: A total of 346 patients underwent 1200 PIPAC treatments in the defined time period. Two-thirds of the patients completed 3 or more PIPAC procedures, and 2 patients had more than 15 treatment procedures. Reasons for PIPAC cessation were disease progression or complication (56%), reorientation to a potential curative procedure (19%), surgical complications of the procedure (13%), death between procedures (8%) and patient request (3%). PSM origin and receiving 3 or more PIPAC treatments were independently correlated with better survival in the overall population, in the group of ultimately unresectable PSM and after propensity score weighting. CONCLUSION: The main reason for stopping PIPAC treatment in palliative management of PSM is disease progression. When 3 or more PIPAC procedures can be delivered in combination to systemic chemotherapy, survival is significantly improved. Its use should be validated by prospective studies.

The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: Pseudomyxoma Peritonei.

BACKGROUND: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) constitutes the established standard of care for pseudomyxoma peritonei patients. However, the role of HIPEC lacks validation through randomized trials, leading to diverse proposed treatment protocols. This consensus seeks to standardize HIPEC regimens and identify research priorities for enhanced clarity. METHODS: The steering committee applied the patient, intervention, comparator, and outcome method to formulate crucial clinical questions. Evaluation of evidence followed the Grading of Recommendations, Assessment, Development, and Evaluation system. Consensus on HIPEC regimens and research priorities was sought through a two-round Delphi process involving international experts. RESULTS: Out of 90 eligible panelists, 71 (79%) participated in both Delphi rounds, resulting in a consensus on six out of seven questions related to HIPEC regimens. An overwhelming 84% positive consensus favored combining HIPEC with CRS, while a 70% weak positive consensus supported HIPEC after incomplete CRS. Specific HIPEC regimens also gained consensus, with 53% supporting Oxaliplatin 200 mg/m2 and 51% favoring the combination of cisplatin (CDDP) associated with mitomycin-C (MMC). High-dose MMC regimens received an 89% positive recommendation. In terms of research priorities, 61% of panelists highlighted the importance of studies comparing HIPEC regimens post CRS. The preferred regimens for such studies were the combination of CDDP/MMC and high-dose MMC. CONCLUSIONS: The consensus recommends the application of HIPEC following CRS based on the available evidence. The combination of CDDP/MMC and high-dose MMC regimens are endorsed for both current clinical practice and future research efforts.

[RENAPE network: Towards more equitable access to care and expertise for patients with rare peritoneal cancers]. / Réseau RENAPE : vers une meilleure équité d'accès aux soins et à l'expertise pour les patients atteints de cancers rares du péritoine.

Since its creation in 2010, the progressive structuration of the RENAPE network (Réseau national de prise en charge des tumeurs rares du péritoine) supported by the "Institut national du cancer" and the "Direction générale de l'offre de soins", allowed the optimization of the healthcare system involved in the management of the rare cancers of the peritoneum. In this setting, the RENA-PATH group has also been reinforced, notably by its recognized diagnostic expertise in pathology and its interface with the MESOPATH group. Moreover RENAPE and RENA-PATH led to guidelines diffusion through the integration, in 2019, to the ``Thesaurus National de Cancérologie Digestive'' (TNCD) and to post-university medical education programs. The aim of this article is to highlight the missions of the RENAPE and RENA-PATH, notably the equity in terms of expertise, access to the networks and their improvement in the management of peritoneal diseases.

Lower airway microbiota compositions differ between influenza, COVID-19 and bacteria-related acute respiratory distress syndromes.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is responsible for 400,000 deaths annually worldwide. Few improvements have been made despite five decades of research, partially because ARDS is a highly heterogeneous syndrome including various types of aetiologies. Lower airway microbiota is involved in chronic inflammatory diseases and recent data suggest that it could also play a role in ARDS. Nevertheless, whether the lower airway microbiota composition varies between the aetiologies of ARDS remain unknown. The aim of this study is to compare lower airway microbiota composition between ARDS aetiologies, i.e. pulmonary ARDS due to influenza, SARS-CoV-2 or bacterial infection. METHODS: Consecutive ARDS patients according to Berlin's classification requiring invasive ventilation with PCR-confirmed influenza or SARS-CoV-2 infections and bacterial infections (> 105 CFU/mL on endotracheal aspirate) were included. Endotracheal aspirate was collected at admission, V3-V4 and ITS2 regions amplified by PCR, deep-sequencing performed on MiSeq sequencer (Illumina®) and data analysed using DADA2 pipeline. RESULTS: Fifty-three patients were included, 24 COVID-19, 18 influenza, and 11 bacterial CAP-related ARDS. The lower airway bacteriobiota and mycobiota compositions (ß-diversity) were dissimilar between the three groups (p = 0.05 and p = 0.01, respectively). The bacterial α-diversity was significantly lower in the bacterial CAP-related ARDS group compared to the COVID-19 ARDS group (p = 0.04). In contrast, influenza-related ARDS patients had higher lung mycobiota α-diversity than the COVID-19-related ARDS (p = 0 < 01). CONCLUSION: Composition of lower airway microbiota (both microbiota and mycobiota) differs between influenza, COVID-19 and bacterial CAP-related ARDS. Future studies investigating the role of lung microbiota in ARDS pathophysiology should take aetiology into account.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy to Treat Pseudomyxoma Peritonei of Ovarian Origin: A Retrospective French RENAPE Group Study.

BACKGROUND: Ovarian pseudomyxoma peritonei (OPMP) are rare, without well-defined therapeutic guidelines. We aimed to evaluate cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat OPMP. METHODS: Patients from the French National Network for Rare Peritoneal Tumors (RENAPE) database with proven OPMP treated by CRS/HIPEC and with histologically normal appendix and digestive endoscopy were retrospectively included. Clinical and follow-up data were collected. Histopathological and immunohistochemical features were reviewed. RESULTS: Fifteen patients with a median age of 56 years were included. The median Peritoneal Cancer Index was 16. Following CRS, the completeness of cytoreduction (CC) score was CC-0 for 9/15 (60%) patients, CC-1 for 5/15 (33.3%) patients, and CC-2 for 1/15 (6.7%) patients. The median tumor size was 22.5 cm. After pathological review and immunohistochemical studies, tumors were classified as Group 1 (mucinous ovarian epithelial neoplasms) in 3/15 (20%) patients; Group 2 (mucinous neoplasm in ovarian teratoma) in 4/15 (26.7%) patients; Group 3 (mucinous neoplasm probably arising in ovarian teratoma) in 5/15 (33.3%) patients; and Group 4 (non-specific group) in 3/15 (20%) patients. Peritoneal lesions were OPMP pM1a/acellular, pM1b/grade 1 (hypocellular) and pM1b/grade 3 (signet-ring cells) in 13/15 (86.7%), 1/15 (6.7%) and 1/15 (6.7%) patients, respectively. Disease-free survival analysis showed a difference (p = 0.0463) between OPMP with teratoma/likely-teratoma origin (groups 2 and 3; 100% at 1, 5, and 10 years), and other groups (groups 1 and 4; 100%, 66.6%, and 50% at 1, 5, and 10 years, respectively). CONCLUSION: These results suggested that a primary therapeutic strategy using complete CRS/HIPEC for patients with OPMP led to favorable long-term outcomes.

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.

Epidemiology of psychiatric disorders following cytoreductive surgeries plus hyperthermic intraperitoneal chemotherapy: a prospective cohort analysis.

The peritoneal surface malignancy (PSM) is an advanced disease, the prognosis of which has been radically improved since the development of cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). These procedures are associated with many complications. However, very few data are available regarding the psychiatric morbidities that might occur. The present study assessed the epidemiology of depressive mood and anxiety during the 6 months following the procedure. The analysis of a prospective cohort that included patients who underwent CRS with or without HIPEC between December 2016 and December 2019 was performed. A total of 115 patients were included. During the 6-months follow-up, the mean (SD) Hospital Anxiety and Depression Scale -D (HADS-D) score was 7.8 (48) and a significant increase compared with the pre-operative period (t(49) = - 4.36, p < 0.005) was found. Thirty-seven patients (32%) had a HADS-D score higher than 7. The incidence of a HADS-D score higher than 7 during the follow-up was 0.05 patient per patient-month. Anxiety and the overall mental disorders intensity scores also increased. The results showed an important increase of mental disorders and their intensity during the 6-months following a CRS with or without HIPEC.

2022 PSOGI Consensus on HIPEC Regimens for Peritoneal Malignancies: Diffuse Malignant Peritoneal Mesothelioma.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and aggressive primary peritoneal disease, with recommended treatment, in eligible patients, of a combination of complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). As treatment is multimodal, there is a wide heterogeneity of HIPEC protocols precluding clear comparisons. Standardization at an international level is required. METHODS: The Peritoneal Surface Oncology Group International (PSOGI) designated a steering committee to produce consensus recommendations for HIPEC regimens, adapted to each etiology. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology was used, based on a systematic review focused on main outcomes related to HIPEC regimens in DMPM patients and on the patient, intervention, comparator, and outcome (PICO) method to elaborate main questions. An opinion survey was added. Furthermore, a Delphi process was performed with voting from a panel of international experts. RESULTS: Eleven questions were elaborated, including two for future research requirements and three to assess the HIPEC regimen preference of the panel. The level of evidence underlying questions was globally low. Overall, 75 (86%) and 67 (77%) of the 87 invited experts completed the vote at the first and second round, respectively. HIPEC following complete CRS was strongly supported by 88% of voters with no need to plan comparative studies with CRS alone for 61.2% of voters. Bi-drug regimens appeared to be preferred to mono-drug ones and cisplatin was globally favored. The opinion survey confirmed the combination of cisplatin and doxorubicin as the recommended regimen. CONCLUSION: International consensus confirmed the indication of HIPEC following complete CRS in DMPM patients and recommended cisplatin-doxorubicin as the first-line HIPEC regimen.

Peritoneal Mesothelioma: Systematic Review of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Protocol Outcomes.

Diffuse malignant peritoneal mesothelioma (DMPM) prognosis was improved by the locoregional treatment combining cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC is a multiparametric treatment with multiple protocols proposed and reviewed in this work. A systematic review of medical literature was performed according to PRISMA guidelines. The search strategy used "malignant peritoneal mesothelioma" and "HIPEC" as keywords in three databases. Studies were included if reporting precisely the HIPEC regimen and the related outcomes, if comparing regimen, or if reporting national/international guidelines. The GRADE methodology was used to rate the level of evidence. Twenty-eight studies were included in this review: 1 was a meta-analysis, 18 reported cohort outcomes, 4 retrospectively compared HIPEC regimens, and 5 were guidelines. Six HIPEC regimens were found, 4 with one drug (cisplatin, mitomycine-C, carboplatin, oxaliplatin), 2 using two drugs (cisplatin-doxorubicin or cisplatin-mitomycine-C). Cisplatin, up to 250 mg/m2 over 90 min, appeared as the key HIPEC drug with a toxicity profile well controlled by the concomitant intravenous perfusion of sodium thiosulfate. Comparative studies tended to show that a bi-drug regimen led to better long-term oncologic outcomes, with cisplatin 50 mg/m2 plus doxorubicin 15 mg/m2 being safe and more efficient. This late protocol was the most widely used and recommended in 3 out of 4 international guidelines. Cisplatin was the preferred drug for HIPEC in DMPM patients. Most of the time, it was combined with doxorubicin for 90 min. A harmonization of protocols and further comparative studies are needed to optimize HIPEC regimen choice.

Primary Peritoneal Hepatoid Adenocarcinoma Patients Treated by Complete Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

Hepatoid adenocarcinoma (HAC) is an extremely rare disease, which could develop from any thoraco-abdominal organ and which exhibits features mimicking hepatocellular carcinoma (HCC). Its diagnosis is thus highly challenging, so is the treatment of that disease. So far, 12 cases have been reported in the literature as issued from the peritoneum. These primary peritoneal HAC were associated with a dismal prognosis and heterogenous management. Two additional cases were described here, managed in a multidisciplinary way as rare peritoneal surface malignancies in an expert center, following the strategy based on a comprehensive tumor burden extension assessment and a radical approach combining iterative complete cytoreductive surgeries followed by hyperthermic intra-peritoneal chemotherapy (HIPEC) and limited systemic chemotherapy sequences. In particular, the choline PET-CT scan guided surgical exploration to reach a complete resection. The oncologic outcomes were promising with a first patient dying 111 months after the diagnosis and a second patient still alive at 43 months.

Determining a minimum data set for reporting clinical and radiologic data for pseudomyxoma peritonei.

Objectives: Pseudomyxoma peritonei (PMP) is a rare cancer currently affecting over 11,736 patients across Europe. Since PMP is so uncommon, collaboration between scientific centers is key to discovering the mechanisms behind the disease, efficient treatments, and targets pointing to a cure. To date, no consensus has been reached on the minimum data that should be collected during PMP research studies. This issue has become more important as biobanking becomes the norm. This paper begins the discussion around a minimum data set that should be collected by researchers through a review of available clinical trial reports in order to facilitate collaborative efforts within the PMP research community. Content: A review of articles from PubMed, CenterWatch, ClinicalTrials.gov and MedRxiv was undertaken, and clinical trials reporting PMP results selected. Summary: There is a core set of data that researchers report, including age and sex, overall survival, peritoneal cancer index (PCI) score, and completeness of cytoreduction, but after this, reports become variable. Outlook: Since PMP is a rare disease, it is important that reports include as large of a number of standardised data points as possible. Our research indicates that there is still much ground to cover before this becomes a reality.

Influence of Extraperitoneal Metastases on the Curative-Intent Management of Colorectal Peritoneal Metastases.

BACKGROUND: Selected patients with colorectal cancer peritoneal metastasis (CRPM) and extraperitoneal disease could be treated radically with a multimodal approach combining complete cytoreductive surgery, thermoablation, radiotherapy, and systemic and intraperitoneal chemotherapy. The impact of extraperitoneal metastatic sites (EPMS) in this setting remains unclear. PATIENTS AND METHODS: Patients with CRPM undergoing complete cytoreduction in 2005-2018 were grouped in: peritoneal disease only (PDO), one EPMS (1 + EPMS), two or more EPMS (2 + EPMS). A retrospective analysis compared overall survival (OS) and postoperative outcomes. RESULTS: Of 433 patients, 109 had 1 + EPMS and 31 had 2 + EPMS. Overall, 101 patients had liver metastasis, 19 lung metastasis, and 30 retroperitoneal lymph node (RLN) invasion. The median OS was 56.9 months. There was no significant OS difference between PDO and 1 + EPMS groups (64.6 and 57.9 months, respectively), whereas OS was lower in the 2 + EPMS group (29.4 months, p = 0.005). In multivariate analysis, 2 + EPMS [hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.33-6.12, p = 0.007], Sugarbaker's Peritoneal Carcinomatosis Index (PCI) > 15 (HR 3.86, 95% CI 2.04-7.32, p < 0.001), poorly differentiated tumors (HR 2.62, 95% CI 1.21-5.66, p = 0.015), and BRAF mutation (HR 2.10, 95% CI 1.11-3.99, p = 0.024) were independent poor prognostic factors, while adjuvant chemotherapy was beneficial (HR 0.33, 95% CI 0.20-0.56, p < 0.001). Patients with liver resection did not show higher severe complication rates. CONCLUSION: In patients with CRPM selected for a radical surgical approach, limited extraperitoneal disease involving one site, notably the liver, does not seem to significantly impair postoperative results. RLN invasion appeared as a poor prognostic factor in this population.

Dynamics of the digestive acquisition of bacterial carriage and integron presence by French preterm newborns according to maternal colonization: The DAIR3N multicentric study.

Objectives: The study aimed to describe the dynamics and risk factors of Gram-negative bacteria (GNB) acquisition in preterm infants. Methods: This prospective multicenter French study included mothers hospitalized for preterm delivery and their newborns, followed until hospital discharge. Maternal feces and vaginal fluids at delivery, and neonatal feces from birth to discharge were tested for cultivable GNB, potential acquired resistance, and integrons. The primary outcome was the acquisition of GNB and integrons in neonatal feces, and their dynamics, evaluated by survival analysis using the actuarial method. Risk factors were analyzed using Cox models. Results: Two hundred thirty-eight evaluable preterm dyads were included by five different centers over 16 months. GNB were isolated in 32.6% of vaginal samples, with 15.4% of strains producing extended-spectrum beta-lactamase (ESBL) or hyperproducing cephalosporinase (HCase), and in 96.2% of maternal feces, with 7.8% ESBL-GNB or HCase-GNB. Integrons were detected in 40.2% of feces and 10.6% of GNB strains. The mean (SD) length of stay of newborns was 39.5 (15.9) days; 4 died in the hospital. At least one infection episode occurred in 36.1% of newborns. The acquisition of GNB and integrons was progressive from birth to discharge. At discharge, half of newborns had ESBL-GNB or HCase-GNB, independently favored by a premature rupture of membranes (Hazard Ratio (HR), 3.41, 95% confidence interval (CI), 1.71; 6.81), and 25.6% had integrons (protective factor: multiple gestation, HR, 0.367, 95% CI, 0.195; 0.693). Conclusion: In preterm newborns, the acquisitions of GNB, including resistant ones, and integrons are progressive from birth to discharge. A premature rupture of membranes favored the colonization by ESBL-GNB or Hcase-GNB.