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.

E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. METHODS: A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. RESULTS: Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2- to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. CONCLUSION: These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.

Liver surgery is an effective treatment for liver tumours. Liver failure is a major problem in patients with a poor liver quality or having large operations. The treatment options for liver failure are limited, with high death rates. To estimate patient risk, assessing liver function before surgery is important. Many methods exist for this purpose, including functional, blood, and imaging tests. This guideline summarizes the available literature and expert opinions, and aids clinicians in planning safe liver surgery.

A prediction model to refine the timing of an early second-look laparoscopic exploration in patients with colon cancer at high risk of early peritoneal metastasis recurrence.

BACKGROUND: In patients at high risk of peritoneal metastasis (PM) recurrence following surgical treatment of colon cancer (CC), second-look laparoscopic exploration (SLLE) is mandatory; however, the best timing is unknown. We created a tool to refine the timing of early SLLE in patients at high risk of PM recurrence. METHODS: This international cohort study included patients who underwent CC surgery between 2009 and 2020. All patients had PM recurrence. Factors associated with PM-free survival (PMFS) were assessed using Cox regression. The primary endpoint was early PM recurrence defined as a PMFS of <6 months. A model (logistic regression) was fitted and corrected using bootstrap. RESULTS: In total, 235 patients were included. The median PMFS was 13 (IQR, 8-22) months, and 15.7% of the patients experienced an early PM recurrence. Synchronous limited PM and/or ovarian metastasis (hazard ratio [HR]: 2.50; 95% confidence interval [CI]: [1.66-3.78]; p < 0.001) were associated with a very high-risk status requiring SLLE. T4 (HR: 1.47; 95% CI: [1.03-2.11]; p = 0.036), transverse tumor localization (HR: 0.35; 95% CI: [0.17-0.69]; p = 0.002), emergency surgery (HR: 2.06; 95% CI: [1.36-3.13]; p < 0.001), mucinous subtype (HR: 0.50; 95% CI [0.30, 0.82]; p = 0.006), microsatellite instability (HR: 2.29; 95% CI [1.06, 4.93]; p = 0.036), KRAS mutation (HR: 1.78; 95% CI: [1.24-2.55]; p = 0.002), and complete protocol of adjuvant chemotherapy (HR: 0.93; 95% CI: [0.89-0.96]; p < 0.001) were also prognostic factors for PMFS. Thus, a model was fitted (area under the curve: 0.87; 95% CI: [0.82-0.92]) for prediction, and a cutoff of 150 points was identified to classify patients at high risk of early PM recurrence. CONCLUSION: Using a nomogram, eight prognostic factors were identified to select patients at high risk for early PM recurrence objectively. Patients reaching 150 points could benefit from an early SLLE.

Feasibility and Safety of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy With or Without Intraoperative Intravenous 5-Fluorouracil and Leucovorin for Colorectal Peritoneal Metastases: A Multicenter Comparative Cohort Study.

BACKGROUND: This retrospective multicenter cohort study compared the feasibility and safety of oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-Ox) with or without intraoperative intravenous 5-fluorouracil (5-FU) and leucovorin (L). METHODS: Our study included consecutive patients with histologically proven unresectable and isolated colorectal peritoneal metastases (cPM) treated with PIPAC-Ox in seven tertiary referral centers between January 2015 and April 2020. Toxicity events and oncological outcomes (histological response, progression-free survival, and overall survival) were compared between patients who received intraoperative intravenous 5-FU/L (PIPAC-Ox + 5-FU/L group) and patients who did not (PIPAC-Ox group). RESULTS: In total, 101 patients (263 procedures) were included in the PIPAC-Ox group and 30 patients (80 procedures) were included in the PIPAC-Ox + 5-FU/L group. Common Terminology Criteria for Adverse Events v4.0 grade 2 or higher adverse events occurred in 48 of 101 (47.5%) patients in the PIPAC-Ox group and in 13 of 30 (43.3%) patients in the PIPAC-Ox + 5-FU/L group (p = 0.73). The complete histological response rates according to the peritoneal regression grading score were 27% for the PIPAC-Ox + 5-FU/L group and 18% for the PIPAC-Ox group (p = 0.74). No statistically significant differences were observed in overall or progression-free survival between the two groups. CONCLUSIONS: The safety and feasibility of PIPAC-Ox + 5-FU/L appears to be similar to the safety and feasibility of PIPAC-Ox alone in patients with unresectable cPM. Oncological outcomes must be evaluated in larger studies.

Laparoscopic cytoreductive surgery and HIPEC in LAMN with small volume of peritoneal disease: a valuable option of treatment for good patient-related experience measures (PREMs).

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the best effective treatment for pseudomyxoma peritonei (PMP). In the last years, the advances in histopathology have stratified PMP lesions in different degrees of aggressivity suggesting the possibility of a tailored treatment. In a subset of patients with small volume peritoneal disease, laparoscopic CRS and HIPEC is feasible. The aim of this study is to analyze the results of laparoscopic CRS + HIPEC in a monocentric series of patients under patient-related experience measures (PREMs). METHODS: All consecutive patients who underwent laparoscopic CRS-HIPEC with curative intent at Cancer Institute of Montpellier were retrieved from a prospectively maintained database and analyzed. Selection criteria for laparoscopic approach were low-grade PMP with pathological confirmation prior to CRS-HIPEC, age < 75 years, no extra-peritoneal disease, peritoneal cancer index (PCI) < 10, and a limited history of abdominal surgery. A PREMS interview was conducted before analysis with all the included patients. Outcomes of interest included postoperative morbidity, medium-term survival, and PREMs. RESULTS: Fourteen patients were operated on for low-grade PMP with a laparoscopic approach at our institution. Conversions to laparotomy were necessary in three patients, and postoperative complications were observed in three patients (Clavien 3b in one patient). In-hospital postoperative median stay was 9.5 days. No death or recurrence was observed during the study period. CONCLUSIONS: Laparoscopic CRS-HIPEC for LAMN in presence of small peritoneal disease is feasible in terms of postoperative morbidity and mortality. According to our PREMs questionnaire, patients' expectations were satisfied.

Half of Postoperative Deaths After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Could be Preventable: A French Root Cause Analysis on 5562 Patients.

OBJECTIVE: To perform a retrospective root-cause analysis of postoperative death after CRS and HIPEC procedures. BACKGROUND: The combination of CRS and HIPEC is an effective therapeutic strategy to treat peritoneal surface malignancies, however it is associated with significant postoperative mortality. METHODS: All patients treated with a combination of CRS and HIPEC between January 2009 and December 2018 in 22 French centers and died in the hospital, were retrospectively analyzed. Perioperative data of the 101 patients were collected by a local senior surgeon with a sole junior surgeon. Three independent experts investigated the typical root cause of death and provided conclusions on whether postoperative death was preventable (PREV group) or not (NON-PREV group). A typical root cause of preventable postoperative death was classified on a cause-and-effect diagram. RESULTS: Of the 5562 CRS+HIPEC procedures performed, 101 in-hospital deaths (1.8%) were identified, of which a total of 18 patients of 70 years old and above and 20 patients with ASA score of 3. Etiology of peritoneal disease was mainly colorectal. A total of 54 patients (53%) were classified in the PREV group and 47 patients (47%) in the NON-PREV group. The results of the study show that in the PREV group, WHO performance status 1-2 was more frequent and the Median Peritoneal Cancer Index was higher compared with those of the NON-PREV group. The cause of death in the PREV group was classified as: (i) preoperatively for debatable indication (59%), (ii) intraoperatively (30%) and (iii) postoperatively in 17 patients (31%). A multifactorial cause of death was found in 11 patients (20%). CONCLUSION: More than half of the postoperative deaths after combined CRS and HIPEC may be preventable, mainly by following guidelines regarding preoperative selection of the patients and adequate intraoperative decisions.

Pressurized Intraperitoneal Aerosol Chemotherapy Enhanced by Electrostatic Precipitation (ePIPAC) for Patients with Peritoneal Metastases.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new mode of intraperitoneal chemotherapy administration that can potentially be improved by the addition of electrostatic precipitation (ePIPAC). This study aimed to describe the procedural details of ePIPAC and to analyze its safety for patients with nonresectable peritoneal metastasis as well as their tolerance and response to this treatment. METHODS: This retrospective cohort study included consecutive patients treated with ePIPAC in three centers from April 2019 to April 2020. The toxicities of each patient were assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Complications were documented according to the Clavien classification. Quality of life (QoL) was assessed using EORTC-QLQ-C30, and the peritoneal regression grading score (PRGS) was used to grade histologic responses. Further surrogates for responses were the Peritoneal Cancer Index (PCI), ascites, and symptoms. RESULTS: Overall, 69 patients received 147 ePIPACs with oxaliplatin (n = 34) or cisplatin/doxorubicin (n = 35) mainly for colorectal (n = 25), ovarian (n = 14), and gastric (n = 13) primary cancers. Systemic chemotherapy was used in the treatment of 54 patients (76%). The median electrostatic therapy time was 12 min (range 6-30 min). The overall and major CTCAE toxicity rates were respectively 24.6% and 15.9%. The postoperative complications rate according to Clavien classification was 4.7%. The responses of 22 patients who had three or more ePIPAC treatments were evaluated as follows: PCI (16 vs 14; p = 0.4), ascites (320 vs 98 ml; p = 0.1), and PRGS (2.23 vs 1.73; p = 0.15). The complete (PRGS1) and major (PRGS2) histologic responses at the third ePIPAC were respectively 38.5% and 53.8%. Overall QoL was stable during the first ePIPACs. CONCLUSION: Repetitive ePIPACs were safe and well tolerated for patients with unresectable peritoneal metastasis.

Evaluation of the environmental contamination and exposure risk in medical/non-medical staff after oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a technique to directly deliver chemotherapeutic drugs in the abdomen for the treatment of peritoneal metastases. Pressurization improves the treatment efficacy but increases the risk of exposure for the medical/non-medical staff who can be exposed by dermal or ocular contact, or inhalation of aerosols containing the cytotoxic drugs. The aim of this study was to evaluate the risk of exposure for the medical/non-medical staff (nurses, surgeons, anaesthesiologists and cleaning personnel; n = 13) during PIPAC with oxaliplatin performed according to the protocol recommended in France. Blood samples were collected 1 h before and immediately after PIPAC, and urine samples 1 h before, and then 3 h and the morning after PIPAC. In the control, non-exposed group (n = 7), only one urine and blood sample were collected. Surface contamination in the operating room was assessed in water- and Surfanios-impregnated wipe samples. The total elemental platinum in each sample was quantified by inductively coupled plasma mass spectrometry, using a method adapted to quantify trace amounts (ng.L-1) in very low volumes (100 µl). No surface contamination was detected. Although 25% of urine samples in the exposed group contained platinum, no statistical difference was observed in urine and plasma samples collected before and after PIPAC and with the control group samples. These findings suggest that the French PIPAC protocol does not increase the risk of exposure to platinum in all staff categories involved. This protocol could be considered in future occupational policies and consensus statements. Trial registration: NCT04014426.

Multicystic peritoneal mesothelioma treated with cytoreductive surgery followed or not by hyperthermic intraperitoneal chemotherapy: results from a large multicentric cohort.

BACKGROUND: Multicystic peritoneal mesothelioma (MCPM) is a rare, slowly growing, condition prone to recur after surgery. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) added to complete cytoreductive surgery (CRS) remains controversial and difficult to assess. As patients are mostly reproductive age women, surgical approach, and fertility considerations are important aspects of the management. This observational retrospective review aimed to accurate treatment strategy reflections. METHODS: The RENAPE database (French expert centers network) was analyzed over a 1999-2019 period. MCPM patients treated with CRS were included. A special focus on HIPEC, mini-invasive approach, and fertility considerations was performed. RESULTS: Overall 60 patients (50 women) were included with a median PCI of 10 (4-14) allowing 97% of complete surgery, followed by HIPEC in 82% of patients. A quarter of patients had a laparoscopic approach. Twelve patients (20%) recurred with a 3-year recurrence free survival of 84.2% (95% confidence interval 74.7-95.0). The hazard of recurrence was numerically reduced among patients receiving HIPEC, however, not statistically significant (hazard ratio 0.41, 0.12-1.42, p = 0.200). A severe post-operative adverse event occurred in 22% of patients with five patients submitted to a subsequent reoperation. Among four patients with a childbearing desire, three were successful (two had a laparoscopic-CRS-HIPEC and one a conventional CRS without HIPEC). CONCLUSION: MCPM patients treatment should aim at a complete CRS. The intraoperative treatment options as laparoscopic approach, fertility function sparing and HIPEC should be discussed in expert centers to propose the most appropriate strategy.

Social media in surgery: evolving role in research communication and beyond.

PURPOSE: To present social media (SoMe) platforms for surgeons, how these are used, with what impact, and their roles for research communication. METHODS: A narrative review based on a literature search regarding social media use, of studies and findings pertaining to surgical disciplines, and the authors' own experience. RESULTS: Several social networking platforms for surgeons are presented to the reader. The more frequently used, i.e., Twitter, is presented with details of opportunities, specific fora for communication, presenting tips for effective use, and also some caveats to use. Details of how the surgical community evolved through the use of the hashtag #SoMe4Surgery are presented. The impact on gender diversity in surgery through important hashtags (from #ILookLikeASurgeon to #MedBikini) is discussed. Practical tips on generating tweets and use of visual abstracts are presented, with influence on post-production distribution of journal articles through "tweetorials" and "tweetchats." Findings from seminal studies on SoMe and the impact on traditional metrics (regular citations) and alternative metrics (Altmetrics, including tweets, retweets, news outlet mentions) are presented. Some concerns on misuse and SoMe caveats are discussed. CONCLUSION: Over the last two decades, social media has had a huge impact on science dissemination, journal article discussions, and presentation of conference news. Immediate and real-time presentation of studies, articles, or presentations has flattened hierarchy for participation, debate, and engagement. Surgeons should learn how to use novel communication technology to advance the field and further professional and public interaction.

Social Media for the Hepato-Pancreato-Biliary community (#SoMe4HPB): connecting a specialized online group for scientific and clinical knowledge dissemination.

BACKGROUND: Social media has an increasingly important role in scientific communication, clinical discussions and knowledge distribution. While several surgical disciplines have taken to internet for increased connectivity, there is currently little knowledge about the social media activity in the field of hepatopancreatobiliary surgery. We aimed to evaluate the implementation and use of a specific HPB hashtag and Twitter handle. METHODS: The hashtag and Twitter handle (#SoMe4HPB; @hpb_so) were initiated on February 2019. We evaluated the response during the initial 15 months by applying NodeXL to trace activity. RESULTS: The Twitter handle had 1388 followers (by May 7, 2020) and had generated 855 tweets and retweets. A total of 1120 mentions of 182 accounts were recorded in original tweets by @hpb_so. The largest global reach was recorded in December 2019 (254.000 people). Pancreatic cancer was the subject of 15% of all posts, liver malignancies of 12% of all posts and minimally invasive surgery of 8%. CONCLUSION: The Social Media for the Hepato-Pancreato-Biliary community (#SoMe4HPB) and its associated Twitter handle @hpb_so had a well-built inception followed by a progressive development connecting individuals interested in HPB Surgery internationally. The involvement of more actors is required in order to fully attain its scientific dissemination role.

Complete pathologic response after two-stage cytoreductive surgery with HIPEC for bulky pseudomyxoma peritonei: proof of concept.

Introduction: Pseudomyxoma peritonei (PMP) is a rare disease characterized by the progressive accumulation of mucinous ascites and peritoneal implants. The optimal treatment for PMP includes the association of complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). For patients with a large burdensome disease, the completeness of cytoreduction sometimes requires maximal effort surgery. The aim of this article is to provide proof of concept for two stage cytoreductive surgery (CRS) in this category of patients.Methods and materials: A two stage CRS and HIPEC with oxaliplatin was proposed for patients with bulky PMP including important involvement of the serosal surfaces of the bowel or colon who had an impaired nutritional status. The residual disease at the end of the first stage was less than 5 mm of thickness on several implants. Clinical, surgical and histopathological variables were analyzed.Results: All eight patients completed the two-stage strategy. Mortality was nil. One Clavien Dindo grade 3 event occurred in each stage. After a median follow up of 29.5 months, all patients were alive and free of recurrence. All of the patients had histopathological complete response on the specimens obtained from the residual sites during the second stage surgery.Conclusions: Two-stage surgical strategy is feasible for bulky PMP patients and it is associated with little high-grade morbidity and enhanced visceral sparing.

Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study.

BACKGROUND: The introduction of cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improved the prognosis of selected patients with peritoneal mesothelioma (PM). OBJECTIVE: The objective of our study was to evaluate whether different HIPEC agents were associated with different outcomes in patients with PM. METHODS: From the RENAPE database, we selected all patients with histology-proven PM who underwent CRS + HIPEC from 1989 to 2014. Inclusion criteria were age ≤ 80 years, performance status ≤ 2, and no extraperitoneal metastases. RESULTS: Overall, 249 patients underwent CRS + HIPEC for PM. The HIPEC regimen included five chemotherapeutic agents (CAs), consisting of cisplatin, doxorubicin, mitomycin-C, oxaliplatin, and irinotecan. When considering all CAs (alone or in combination), there was no significant statistical difference in regard to postoperative overall survival (OS). However, OS was better when using two CAs (group 2 drugs) versus one CA (group 1 drug) (p = 0.03). The different CA regimens were equally distributed between the two groups. This association between OS and HIPEC agent, as well as a trend for better progression-free survival, were both observed in the two-drug group versus the one-drug group (p = 0.009) for patients undergoing complete cytoreductive surgery (CC-0) with an epithelioid subtype. CONCLUSIONS: This large study seems to show improved OS when combined CAs, especially with platinum-based regimens, are used for HIPEC in patients with PM, but needs to be confirmed by a randomized controlled trial.

[Contribution of intraperitoneal chemotherapy in the treatment of colorectal peritoneal carcinoma. HIPEC, PIPAC, state of the art and future directions]. / La chimiothérapie intra-péritonéale dans le traitement de la carcinose péritonéale d'origine colorectale. CHIP, PIPAC, état des lieux et perspectives.

After more than a decade of good results using the combination of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinosis of colorectal origin, the PRODIGE7 study, which specifically evaluated the role of HIPEC, failed to show any superiority in terms of overall and disease-free survival for the CRS+HIPEC combination compared with CRS alone. This study constituted a radical change in the knowledge and therapeutic attitudes observed to date. After reviewing the literature and the consensus of national and international experts, a synthesis is provided, together with an outlook on the questions raised and the therapeutic trials and innovations of the near future. An analysis of recent advances due to the advent of a new technique, PIPAC, is also proposed, as well as a review of current therapeutic trials in this field.