Survival Analysis and Recurrence Patterns in 555 Patients with Colorectal Peritoneal Metastases Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The presence at diagnosis, or development of, colorectal peritoneal metastases (CPM) is common in colorectal cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) show promising results in selected patients with CPM. The current study aimed to describe oncologic outcomes of patients with CPM, focusing on recurrence patterns and risk factors for adverse events. METHODS: We conducted a retrospective review of patients with CPM treated by CRS and HIPEC at a single institution between 2000 and 2021. RESULTS: A total of 555 patients were included, of whom 480 (86.5%) had complete cytoreduction, with a median age of 59 years and median Peritoneal Cancer Index (PCI) of 6. Following complete cytoreduction, 5-year overall survival (OS) and disease-free survival (DFS) were 51% and 31%, respectively. In multivariable Cox regression, PCI >6 (hazard ratio [HR] 2.25), pathological node positivity (pN+; HR 1.94), and perineural invasion (HR 1.85) were associated with decreased OS, while PCI >6, pN+, and previous systemic metastases resulted in reduced DFS. Overall, 284 (62%) patients developed recurrence, of whom 97 (34%) had local recurrence (LR), 100 (35%) had systemic recurrence (SR), and 87 (31%) had combined recurrence (5-year OS: 49.3%, 46%, and 37.4%, respectively). Mutated KRAS (mKRAS) was associated with lower 5-year OS (55.8%) and DFS (27.9%) compared with wild-type KRAS (wtKRAS; 70.7% and 37.6%, respectively). In multivariable analyses, mKRAS was related to decreased OS (HR 1.82), DFS (HR 1.55), and SR (OS 1.89), but not to LR. CONCLUSIONS: Complete cytoreduction results in good survival outcomes for patients with CPM. Burden of peritoneal disease and tumor biology are the main predictors of survival. Patients with mKRAS are a high-risk cohort, with increased probability of SR and reduced survival.

Predictive Value of C-Reactive Protein for Infectious Complications After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Single-Center Prospective Study.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be associated with significant morbidity and prolonged hospital stay. Postoperative infections account for a high burden of these complications. This study aimed to assess the predictive value of postoperative C-reactive protein (CRP) levels for overall infectious complications and anastomotic leaks. METHODS: This was a single-center prospective study of patients undergoing CRS and HIPEC for peritoneal metastases between 2018 and 2020 at Maisonneuve-Rosemont Hospital in Montreal, QC, Canada. CRP levels were measured daily for 10 days following surgery. A comparison was made between patients with infectious complications and those without. RESULTS: Ninety-nine patients were included. Thirty patients had infectious complications (30.3%) and four patients presented an anastomotic leak (4%). CRP levels were significantly higher in patients with infectious complications from postoperative days (PODs) 2-10. Daily cut-off values most accurately predicted infectious complications on day 8 (94.3 mg/L; area under the curve [AUC] 0.85, sensitivity [SE] 76.2%, specificity [SP] 94.7%, positive predictive value [PPV] 88.9%, negative predictive value [NPV] 87.8%; p < 0.0001) and day 9 (72.7 mg/L; AUC 0.89, SE 95.2%, SP 81.8%, PPV 76.9%, NPV 96.4%; p < 0.0001). Patients with infectious complications had longer operative time, higher peritoneal cancer index, and a higher number of intestinal anastomoses, while their baseline characteristics were comparable. CONCLUSION: Measurement of CRP helps predict infectious complications following CRS and HIPEC, particularly on PODs 8 and 9. Cut-off values are more accurate after the first postoperative week, especially in ruling out infectious complications.

A Clinician's perspective on the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer management.

The prevention of intraperitoneal spread is of utmost importance in the management of advanced ovarian cancer (OC), thus demanding the exploration of innovative treatment techniques. The propensity of OC to spread to the peritoneum has highlighted the potential of local therapy as a promising approach. Among the proposed treatments thus far are several local intraperitoneal therapies, with hyperthermic intraperitoneal chemotherapy (HIPEC) being one of them. The application of HIPEC may potentially enhance the survival rates of patients with OC, as indicated by a recent publication of high-quality prospective data. The incorporation of HIPEC in conjunction with primary cytoreductive surgery (CRS) does not have a significant impact on either overall survival (OS) or disease-free survival (DFS). However, the incorporation of HIPEC alongside interval CRS, followed by systemic chemotherapy (CTH), markedly enhances both OS and DFS. The most recent data also substantiates the effectiveness of HIPEC in recurrent ovarian cancer (ROC), resulting in an improvement of survival outcomes. Additional research will contribute to the improvement of the HIPEC regimen and technique, as well as the precise identification of patients who will gain the most advantage from this treatment approach. It is recommended to discuss and update (inter)national clinical guidelines for managing patients with advanced OC and peritoneal involvement.

Is Hyperthermic Intraperitoneal Chemotherapy Appropriate for Colon Cancer?

Colorectal cancer (CRC) with peritoneal metastases is a complex disease and its management presents significant clinical challenges. In well-selected patients at experienced centers, CRS/hyperthermic intraperitoneal chemotherapy (HIPEC) can be performed with acceptable morbidity and is associated with prolonged survival. Based on the results of recent randomized controlled trials, HIPEC using oxaliplatin after CRS with shortened perfusion periods (30 minutes) is no longer recommended. There is a movement toward utilizing mitomycin C as a first-line intraperitoneal agent with extended perfusion times (90-120 minutes); however, there is currently little prospective evidence to support its widespread use.

The role of multimodality imaging in the selection and management of patients treated with cytoreductive surgery and HIPEC.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is the mainstay of potentially curative surgical treatment for malignancies that have spread to peritoneal surfaces. This surgical procedure is however associated with high morbidity and appropriate patient selection and planning is therefore essential. Available multimodality imaging techniques include CT with oral and intravenous contrast, MRI including use of dedicated peritoneal protocol and FDG-PET/CT. These used with the correct technique, read by specialist radiologists and discussed under the auspices of a dedicated multidisciplinary team, can help to improve outcomes. We demonstrate that imaging not only provides information about peritoneal disease burden but more importantly want to shift the reader's focus to disease distribution. Our examples highlight how imaging helps avoid futile surgery by identifying patients with disease in unfavourable sites and show the strength and limitations of the various imaging modalities. We share how MR imaging can help identify multifocal and often occult sites including widespread miliary disease. Our examples provide a comprehensive overview demonstrating how imaging can help plan surgery by identifying patients who may need splenic vaccinations, counselling for stoma, egg harvesting and input from surgeons with other specialist expertise greatly increasing likelihood of achieving complete cytoreduction.

The impact of Paclitaxel-based hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer patients - interim analysis of safety and immediate efficacy of a randomized control trial (C-HOC trial).

OBJECTIVE: This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial). METHODS: In a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared. RESULTS: Among 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3-4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively. CONCLUSIONS: Combining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.

Systematic Cholecystectomy During Cytoreductive Surgery Plus HIPEC: A Critical Analysis of an Empirical Tradition.

BACKGROUND: Some procedures performed during cytoreductive surgery (CRS) and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) are based on empirical data. One of these procedures is systematic cholecystectomy. This study aimed to perform a critical analysis of the need for systematic cholecystectomy during CRS+HIPEC of patients with peritoneal carcinomatosis using long-term follow-up data. METHODS: Patients with peritoneal surface malignancies who were candidates for CRS+HIPEC and underwent surgery between January 2008 and December 2022 were analyzed. For patients with gallbladder involvement due to the disease or for patients whose preoperative study showed the presence of cholelithiasis, cholecystectomy was performed as part of the surgery, which was avoided for the remaining patients. All postoperative adverse events that occurred in the first 90 days were recorded, and clinical records focused on the development of biliary pathology during the follow-up period were studied. RESULTS: The results from a consecutive series of 443 patients with peritoneal surface malignancies who underwent surgery between January 2008 and December 2022 were analyzed. The average age of the cohort was 50 years. The median follow-up period for the cohort was 41 months (range, 12-180 months), with a disease-free survival of 17 months. For 373 of the patients, CRS+HIPEC was completed without an associated cholecystectomy, and in 16 of them, the appearance of cholelithiasis was detected during the follow-up period. Only two patients in the series showed complications derived from gallstones and required a delayed cholecystectomy. CONCLUSIONS: Although cholecystectomy is a safe procedure in the context of CRS+HIPEC, it is not risk free, and its routine performance may be unnecessary.

Long-Term Outcomes following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Colorectal Origin.

BACKGROUND: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major treatment of colorectal peritoneal carcinomatosis (CPC). The aim was to determine the disease-free survival (DFS) and overall survival (OS) of patients undergoing CRS-HIPEC for CPC and factors associated with long-term survival (LTS). METHODS: consecutive CPC patients who underwent CRS-HIPEC at a HIPEC center between 2007 and 2021 were included. Actual survival was calculated, and Cox proportional hazards models were used to identify factors associated with OS, DFS and LTS. RESULTS: there were 125 patients with CPC who underwent primary CRS-HIPEC, with mean age of 54.5 years. Median follow-up was 31 months. Average intraoperative PCI was 11, and complete cytoreduction (CC-0) was achieved in 96.8%. Median OS was 41.6 months (6-196). The 2-year and 5-year OS were 68% and 24.8%, respectively, and the 2-year DFS was 28.8%. Factors associated with worse OS included pre-HIPEC systemic therapy, synchronous extraperitoneal metastasis, and PCI ≥ 20 (p < 0.05). Progression prior to CRS-HIPEC was associated with worse DFS (p < 0.05). Lower PCI, fewer complications, lower recurrence and longer DFS were associated with LTS (p < 0.05). CONCLUSION: CRS and HIPEC improve OS in CPC patients but they have high disease recurrence. Outcomes depend on preoperative therapy response, extraperitoneal metastasis, and peritoneal disease burden.

Factors affecting dietary progression post cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND & AIMS: Peritoneal carcinomatosis (PC) is treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Timely postoperative nutrition is required to reduce the risk of malnutrition and other complications; thus the present study aims to evaluate factors that may impact dietary progression following CRS/HIPEC treatment. METHODS: Forty-two patients undergoing CRS/HIPEC at a tertiary hospital were audited between April 2019 and August 2020. Patients were classified into two groups: fast dietary progression (FDP) and slow dietary progression (SDP), based on commencement of a full fluid diet (FF) within 7 days or after 7 days postoperatively. Between-group differences in patient characteristics, surgical factors and postoperative complications were evaluated statistically (significant at p < 0.05). RESULTS: FDP and SDP groups comprised of 22 (52%) and 20 (40%) patients, respectively. A FF diet was established on a median of 7 (4.25-9.75) days, but not before day 2. Nineteen of the 31 (61.3%) patients receiving parenteral nutrition (PN) were in the SDP group (p = 0.009). The SDP group had longer surgery duration (p = 0.05), more gastrointestinal anastomoses (GIAs) (p = 0.02), more enterotomies (p = 0.008), higher rates of prolonged ileus (p = 0.007), longer duration to first bowel motion (p = 0.002), more returns to theatre (p = 0.03), higher Clavien Dindo scores ≥ IIIb (p = 0.01) and longer postoperative length-of-stay (p = 0.001), compared to the FDP group. CONCLUSIONS: Postoperative complications were associated with SDP in PC patients undergoing CRS/HIPEC. Strategies that aim to limit SDP through timely commencement of nutrition, including PN, are important to improve postoperative outcomes in this patient group.

Enhanced recovery after surgery (ERAS) implementation in cytoreductive surgery (CRS) and hyperthermic IntraPEritoneal chemotherapy (HIPEC): Insights from Italian peritoneal surface malignancies expert centers.

BACKGROUND: Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a complex procedure that involves extensive peritoneal and visceral resections followed by intraperitoneal chemotherapy. The Enhanced Recovery After Surgery (ERAS) program aims to achieve faster recovery by maintaining pre-operative organ function and reducing the stress response following surgery. A recent publication introduced dedicated ERAS guidelines for CRS and HIPEC with the aim of extending the benefits to patients with peritoneal surface malignancies. METHODS: A survey was conducted among 21 Italian centers specializing in peritoneal surface malignancies (PSM) treatment to assess adherence to ERAS guidelines. The survey covered pre/intraoperative and postoperative ERAS items and explored attitudes towards ERAS implementation. RESULTS: All centers completed the survey, demonstrating expertise in PSM treatment. However, less than 30 % of centers adopted ERAS protocols despite being aware of dedicated guidelines. Preoperative optimization was common, with variations in bowel preparation methods and fasting periods. Intraoperative normothermia control was consistent, but fluid management practices varied. Postoperative practices, including routine abdominal drain placement and NGT management, varied greatly among centers. The majority of respondents expressed an intention to implement ERAS, citing concerns about feasibility and organizational challenges. CONCLUSIONS: The study concludes that Italian centers specialized in PSM treatment have limited adoption of ERAS protocols for CRS ± HIPEC, despite being aware of guidelines. The variability in practice highlights the need for standardized approaches and further evaluation of ERAS applicability in this complex surgical setting to optimize patient care.

Pseudomyxoma peritonei: The struggle of a lifetime and the hope of a cure - a rare diagnosis with review of the literature.

Pseudomyxoma peritonei is a rare pathological condition characterized by mucinous tumor tissue implants on the peritoneal surface. Although the cause of Pseudomyxoma peritonei has been extensively studied, the prevailing agreement is that it stems from mucinous tumors that occur in the ovaries or appendix. The tumor tissue typically remains localized to the peritoneum and does not exhibit extraperitoneal spread. Patients with Pseudomyxoma peritonei may present with symptoms such as abdominal pain, bloating, loss of appetite, and shortness of breath. Computerized Tomography is commonly used for diagnostic purposes. The treatment of Pseudomyxoma peritonei typically involves surgical evacuation of the tumoral tissue, followed by cytoreduction and Hyperthermic Intraperitoneal Chemotherapy. While effective treatment options are available, some patients may require repeated surgeries over an extended period. This paper reports on a case study of a patient with a history of recurrent Pseudomyxoma peritonei, necessitating multiple surgical interventions over a decade. The paper concludes with a review of the relevant literature.

Genetic Clustering of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Patients of Colorectal Origin: KRAS and Not TP53 Cluster Alterations are Associated with Poor Outcomes.

BACKGROUND: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined. OBJECTIVE: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population. METHODS: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics. RESULTS: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05). CONCLUSIONS: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.

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.

Incidentally Diagnosed Low-Grade Primary Peritoneal Serous Carcinoma Within the Umbilical Hernia Sac in a Male: A Report of an Extremely Rare Case and Review of the Literature.

Primary peritoneal serous carcinoma (PPSC) is a rare tumor that develops in the peritoneum. PPSC originates from embryonic nests of Müllerian cells in the peritoneum, which are also present in the epithelium of the ovary. This similarity explains the histopathological resemblance between PPSC and low-grade serous ovarian carcinoma. While PPSC primarily affects women, it is an extremely rare occurrence in males, and it is believed that the significant difference in diagnosis rates between males and females is due to the inhibition of Müllerian system growth by substances produced by male Sertoli cells. These substances are present at higher levels in males, which may prevent the development of Müllerian system-derived tumors in men. We describe a 65-year-old male patient who presented for elective bariatric surgery and umbilical hernia repair, and an incidental finding of low-grade PPSC was made based on hernia sac pathology. The patient underwent further management, including tumor debulking and hyperthermic intraperitoneal chemotherapy (HIPEC), with positive outcomes. Long-term follow-up and oral letrozole treatment are planned.

Critical appraisal of total gastrectomy plus total colectomy with hyperthermic intraperitoneal chemotherapy as a treatment for advanced pseudomyxoma peritonei.

BACKGROUND: The absolute requirement for a long-term favorable result with cytoreductive surgery for pseudomyxoma peritonei is a complete resection of all visible disease. A combination of parietal peritonectomy procedures and visceral resections is required for this to occur. The cytoreductive surgery is supplemented by hyperthermic intraperitoneal chemotherapy. METHODS: We searched our database and secured files for patients who required a total gastrectomy and a total colectomy to achieve a complete cytoreductive surgery. Survival of low-grade mucinous neoplasm (LAMN) and mucinous appendiceal adenocarcinoma (MACA) histologies were determined. Clinical and histologic variables were assessed for their impact on survival. RESULTS: Thirteen of 450 patients (2.9%) with LAMN histology and 14 of 186 patients (7.5%) with MACA histology had these visceral resections. Median survival of these 27 patients was 10 years. LAMN and MACA patients showed the same survival. For LAMN histology, this requirement for extensive visceral resection markedly reduced survival (p < 0.0001). For MACA, there was no adverse impact on survival (p = 0.4359). Class 4 adverse events caused reduced survival (p = 0.0014). CONCLUSIONS: A 10-year median survival accompanies total gastrectomy plus total colectomy for advanced pseudomyxoma peritonei. Systemic chemotherapy and class 4 adverse events reduced survival.

Omental metastases in patients with pseudomyxoma peritonei or colorectal peritoneal metastases - is routine omentectomy justified?

BACKGROUND: The greater omentum is routinely resected during cytoreductive surgery (CRS), but few studies have analyzed the rationale behind this. This study aimed to assess the prevalence of omental metastases (OM) and the correlation between macroscopically suspected and microscopically confirmed OM, in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM). METHOD: All patients without previous omentectomy, treated with initial CRS and hyperthermic intraperitoneal chemotherapy for PMP or colorectal PM, at Uppsala University Hospital in 2013-2021, were included. Macroscopic OM in surgical reports was compared with histopathological analyses. RESULTS: In all, 276 patients were included. In those with PMP, 112 (98%) underwent omentectomy and 67 (59%) had macroscopic suspicion of OM. In 5 (4%) patients, the surgeon was uncertain. Histopathology confirmed OM in 81 (72%). In patients with macroscopic suspicion, 96% had confirmed OM (positive predictive value, PPV). In patients with no suspicion, 24% had occult OM (negative predictive value, NPV = 76%). In patients with colorectal PM, 156 (96%) underwent omentectomy and 97 (60%) had macroscopic suspicion. For 5 (3%) patients, the surgeon was uncertain. OM was microscopically confirmed in 90 (58%). PPV was 85% and NPV was 89%. The presence of OM was a univariate risk factor for death in PMP (HR 3.62, 95%CI 1.08-12.1) and colorectal PM (HR 1.67, 95%CI 1.07-2.60), but not in multivariate analyses. CONCLUSION: OM was common and there was a high risk of missing occult OM in both PMP and colorectal PM. These results support the practice of routine omentectomy during CRS.

Intra-Operative Diagnosis of Benign Multicystic Peritoneal Mesothelioma: A Case Report of Rare Entity and Lessons Learned.

Benign multicystic peritoneal mesothelioma (BMPM), also known as multicystic peritoneal mesothelioma (MCPM), is a rare cystic neoplasm arising from the mesothelium lining of the abdominal and pelvic peritoneum. This entity has been disproportionately described in women of reproductive age. Both the etiology and pathogenesis of the condition are not well understood. Preoperative diagnosis is challenging as differentials are varied and include endometriosis, lymphangioma, pseudomyxoma peritonei, cystic adenomatoid tumor, and malignant peritoneal mesothelioma. Management options include cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy (HIPEC). In this case report, we highlight the complexity of preoperative diagnosis, presentation, workup, treatment, and management of BMPM. We report the case of a female patient presenting with abdominal pain and imagining consistent with cystic intra-abdominal lesions. After an inconclusive percutaneous biopsy and a multi-disciplinary tumor board discussion, the patient was offered CRS with HIPEC. Intra-operative frozen section indicated benign epithelial lined cysts. CRS and HIPEC were performed. After a second opinion, the lesions were confirmed by pathology and immunohistochemistry to be BMPM. In this report, we discuss the gold standard of care for patients with BMPM to improve the disease control rate. This pathway is proposed in our study, and, thus, we conclude that BMPM should be considered in the differential diagnosis of patients presenting with symptomatic multiple intraperitoneal cystic lesions.

Effect of RAS and BRAF mutations on peritoneal metastasis risk and cytoreductive surgery/hyperthermic intraperitoneal chemotherapy efficacy in colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) patients with peritoneal metastasis (CRC-PM) have a worse prognosis than those with liver and lung metastases. Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective locoregional treatment for CRC-PM. To date, the prognostic analysis of CRS/HIPEC mostly focuses on clinical and pathological characteristics; however, genetic characteristics, such as RAS/BRAF mutation status, are not sufficient. This study aimed to systematically assess the correlation between RAS/BRAF status and PM risk, as well as the prognostic efficacy of CRS/HIPEC for CRC. METHOD: This study was written in accordance with the 2020 guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We searched PubMed, EMBASE, and the Cochrane library with the following keywords: "Peritoneal Neoplasms," "raf Kinases" and "ras Proteins". The fixed-effects model and inverse variance method were used for analysis. Odds ratios (OR) and 95 % confidence intervals (CI) were used to reflect the risk of PM associated with RAS/BRAF mutations. Hazard ratios (HR) and 95 % CI were used to evaluate the effects of RAS/BRAF mutations on the prognosis of CRS/HIPEC. RESULT: Eighteen articles included 5567 patients. In the risk analysis of PM, patients with BRAF mutation were more likely to have PM than those with wild-type BRAF (OR = 2.28, 95 % CI = 1.73-3.01, P < 0.001, I2 = 0 %). In contrast, there was no significant difference in the effect of RAS mutation and wild-type on PM of CRC (OR = 1.28, 95 % CI = 0.99-1.66, P = .06, I2 = 0 %). In a prognostic analysis of CRS/HIPEC, RAS mutation predicted poor overall survival (HR = 1.68, 95 % CI = 1.39-2.02, P < 0.001, I2 = 1 %) and disease-free survival (HR = 1.61, 95 % CI = 1.34-1.94, P < 0.001, I2 = 42 %). The results for BRAF mutation was consistent with the prognostic impact of RAS mutation's overall survival (HR = 2.57, 95 % CI = 1.93-3.44, P < 0.001, I2 = 0 %) and disease-free survival (HR = 1.90, 95 % CI = 1.40-2.56, P < 0.001, I2 = 82 %). CONCLUSION: BRAF mutation, rather than RAS mutation, was a high-risk factor for CRC-PM. And both BRAF and RAS mutations negatively affected the prognosis of CRS/HIPEC in CRC-PM patients. Our results could provide suggestions for the selection of comprehensive treatment for CRC-PM with RAS/BRAF mutations.

Radical cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal sarcomatosis: Results from a reference center and considerations based on current evidence.

INTRODUCTION: Peritoneal sarcomatosis is a rare disease, with multiple histological origins and poor overall prognosis. The option of radical cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The results of a surgical team experienced in these procedures are analyzed and discussed based on the available evidence. METHODS: Study on a prospective database of patients with peritoneal sarcomatosis who underwent CRS and HIPEC, from 2016 to 2022, in a national reference center for sarcomas and peritoneal oncological surgery, who met the established inclusion/exclusion criteria. RESULTS: 23 patients were included in the study, with a median age of 53 years (6-68). Recurrent/persistent clinical presentation predominated (78.3%). Visceral origin (including GIST and non-GIST peritoneal) accounted for 47.8% of patients, compared to 43.5% uterine and 8.7% retroperitoneal. The median PCI was 17 (3-36), with CC0 cytoreduction of 87%. Postoperative morbidity (Dindo Clavien III-IV) of 13%, with no postoperative mortality in the series. Overall survival and disease-free survival at 5 years were 64% and 34%, respectively. Histological grade was the most influential prognostic factor for survival. CONCLUSIONS: The results of the series, with low morbidity, support the benefit of radical peritoneal oncological surgery in patients with peritoneal sarcomatosis after adequate selection, as long as it is performed in high-volume centers, experienced surgeons and expert multidisciplinary teams. However, the role of HIPEC remains to be demonstrated and pending future studies.

No Indication for Routine Resection of Surgical Scars during Cytoreductive Surgery and HIPEC.

BACKGROUND: Careful macroscopic assessment of surgical scars is needed to avoid routine scar resection during cytoreductive surgery (CRS) for peritoneal metastases (PM). This study aimed to analyze the correlation between macroscopically suspected and microscopically confirmed scar metastases (SMs), and to analyze the prognostic impact of not undergoing routine scar resection. METHOD: All patients with previous surgery, treated with CRS and hyperthermic intraperitoneal chemotherapy, for colorectal PM or pseudomyxoma peritonei (PMP), at Uppsala University Hospital in 2013-2021, were included. Macroscopic SMs in surgical reports were compared with histopathological analyses. RESULTS: In total, 227 patients were included. Among colorectal PM patients (n = 156), SM was macroscopically suspected in 41 (26%) patients, and 63 (40%) underwent scar resection. SM was confirmed in 19 (30%). Among patients with macroscopic suspicion, 45% had confirmed SM (positive predictive value, PPV). A total of 1 of 23 (4%) patients with no macroscopic suspicion had SM (negative predictive value, NPV = 96%). Among the PMP patients (n = 71), SM was macroscopically suspected in 13 (18%), and 28 (39%) underwent scar resection, of whom 12 (43%) had SM. The PPV was 77%. Occult SM was found in 1 of 14 (NPV = 93%). Not undergoing routine scar resection did not affect recurrence-free survival (RFS, p = 0.2) or overall survival (OS, p = 0.1) in colorectal PM patients or PMP patients (RFS p = 0.7, OS p = 0.7). CONCLUSION: Occult SM is uncommon and scar resection does not affect RFS or OS. Therefore, macroscopically benign-appearing scars can be left without resection, though resection should be performed upon suspicion or uncertainty.