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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. [ABSTRACT FROM AUTHOR]

The prognostic significance of positive peritoneal cytology still varied between cancer types and geographical origin. However, because of the lack of sensitivity of this biomarker, conventional cytology is not routinely performed in every country. Here, we wanted to test a new biomarker, peritoneal tumour DNA, using NGS technique, in order to compare it with the historical one, in patients having peritoneal metastases of gastrointestinal or ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Addition of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery (CRS) in the treatment of peritoneal metastases of colorectal origin (CRPM) did not show any survival benefit in the PRODIGE 7 trial (P7). This study aimed to investigate whether perioperative outcomes after CRS alone for CRPM patients is mediated by hospital volume and to determine the effect of P7 on French practice for CRPM patients treated respectively with CRS alone and CRS/HIPEC. Methods: Data from CRPM patients treated with CRS alone between 2013 and 2020 in France were collected through a national medical database. The study used a cutoff value of the annual CRS-alone caseload affecting the 90-day postoperative mortality (POM) determined from our previous study to define low-volume (LV) HIPEC and high-volume (HV) HIPEC centers. Perioperative outcomes were compared between no-HIPEC, LV-HIPEC, and HV-HIPEC centers. The trend between years and HIPEC rates was analyzed using the Cochrane-Armitage test. Results: Data from 4159 procedures were analyzed. The patients treated in no-HIPEC and LV-HIPEC centers were older compared with HV-HIPEC centers (p < 0.0001) and had a higher Elixhauser comorbidity index (p < 0.0001) and less complex surgery (p < 0.0001). Whereas the major morbidity (MM) rate did not differ between groups (p = 0.79), the 90-day POM was lower in HV-HIPEC centers than in no-HIPEC and LV-HIPEC centers (5.4% vs 15% and 13.3%; p < 0.0001), with lower failure-to-rescue (FTR) (p < 0.0001). After P7, the CRS/HIPEC rate decreased drastically in Cancer centers (p < 0.001), whereas patients treated with CRS alone are still referred to expert centers. Conclusions: Centralization of CRS alone should improve patient selection as well as FTR and POM. After P7, CRS/HIPEC decreased mostly in Cancer centers, without any impact on the number of CRS-alone cases referred to expert centers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Secondary treatment of recurrent colorectal peritoneal metastases after previous cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly investigated. Objectives: To evaluate the overall survival outcome of secondary (repeat) CRS + HIPEC compared to palliative treatment in recurrent peritoneal disease. Methods: Patients with colorectal peritoneal metastases treated with an index CRS + HIPEC and subsequently having recurrent peritoneal disease were identified from the prospective Swedish national HIPEC registry. Patients were divided into interventional group (secondary CRS + HIPEC) or palliative group. Multivariable logistic regression, propensity-score matching, and survival outcomes were calculated. Results: Among 575 patients who underwent complete CRS between 2010 and 2021, 208 (36 %) were diagnosed with a subsequent recurrent peritoneal disease. Forty-two patients (20 %) were offered secondary CRS + HIPEC. Propensity-score matching of secondary interventional cases with palliative cases succeeded in 88 % (n = 37) in which female sex, lower peritoneal cancer index at index surgery, longer disease-free interval, and absence of extra-peritoneal metastases were identified as the most relevant matching covariates. Median OS from date of recurrence was 38 months (95%CI 30–58) in the interventional group and 19 months (95%CI: 15–24) in the palliative group (HR 0.35 95%CI: 0.20–0.63, p = 0.0004). Sensitivity analyses confirmed the results. As reference, the median OS from index CRS + HIPEC in the whole colorectal registry (n = 575) was 41 months (95%CI: 38–45). Conclusion: After matching for relevant factors, the hazard ratio for death was significantly reduced in patients who were offered a secondary CRS + HIPEC procedure for recurrent peritoneal disease. Selection bias is inherent, but survival outcomes were comparable to those achieved after the initial procedure.

Simple Summary: Intraperitoneal (IP) administration of Paclitaxel (PTX) is a logical approach for treating peritoneal metastases (PMs), as it allows direct drug infiltration into PMs, providing prolonged exposure at high concentrations with minimal systemic side effects. However, the optimal timing for combining intravenous (IV) and IP administration remains uncertain. This study demonstrated that IP administration of PTX resulted in higher concentrations of PTX in peritoneal tumors, as well as increased levels of intravenously administered Carboplatin (CBDCA) when given four days after PTX administration. These findings suggest that IP PTX may enhance the efficacy of subsequent systemic chemotherapy. Therefore, staggered and repeated systemic chemotherapy following IP PTX appears to be a highly effective strategy for managing PMs. Despite advances in systemic chemotherapy, patients with gastric cancer (GC) and peritoneal metastases (PMs) continue to have poor prognoses. Intraperitoneal (IP) administration of Paclitaxel (PTX) combined with systemic chemotherapy shows promise in treating PMs from GC. However, methods of drug administration need to be optimized to maximize efficacy. In this study, we utilized a mouse model with PMs derived from a human GC cell line, administering PTX either IP or intravenously (IV), and Carboplatin (CBDCA) IV 0, 1, and 4 days after PTX administration. The PMs were resected 30 min later, and concentrations of PTX and CBDCA in resected tumors were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results indicated that PTX concentrations were higher with IP administration than with IV administration, with significant differences observed on days 0 and 1. CBDCA concentrations 4 days post-IP PTX administration were higher than with simultaneous IV PTX administration. These findings suggest that IP PTX administration enhances CBDCA concentration in peritoneal tumors. Therefore, sequential IV administration of anti-cancer drugs appears more effective than simultaneous administration with IP PTX, a strategy that may improve prognoses for patients with PMs. [ABSTRACT FROM AUTHOR]

Multimodal treatment in peritoneal metastases (PM) from colorectal neoplasms may improve overall survival (OS). In this study, we reported our experience in using cytoreductive surgery (CRS) combined with intraperitoneal chemohyperthermia (HIPEC) for the treatment of peritoneal metastases (PM) from colorectal neoplasms. The first aim was to evaluate the overall survival of these patients. Furthermore, using the results of the Prodige 7 Trial and incorporating them with the entropy balance statistical tool, we generated a pseudopopulation on which to test the use of CRS alone. We performed a retrospective analysis based on a prospective database of all 55 patients treated with CRS + HIPEC between March 2004 and January 2023. The median OS was 47 months, with 1-, 3- and 5-year survival rates of 90.8%, 58.7% and 42.7%, respectively. There was no significant difference in the data in the pseudogroup generated with entropy balance. This finding confirms the critical role of complete cytoreduction in achieving the best OS for patients with PM. PCI > 6 seems to be the most important prognostic factor influencing OS. At present, CRS + HIPEC seems to be the therapeutic strategy that guarantees the best results in terms of OS for patients with relatively low PCI and in whom a CCS ≤ 1 can be achieved. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty in the relative benefits and harms of hyperthermic intraoperative peritoneal chemotherapy (HIPEC) when added to cytoreductive surgery (CRS) +/− systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric, or ovarian cancers. Methods: We searched randomized controlled trials (RCTs) in the medical literature until April 14, 2022 and applied methods used for high‐quality systematic reviews. Findings: We included a total of eight RCTs (seven RCTs included in quantitative analysis as one RCT did not provide data in an analyzable format). All comparisons other than ovarian cancer contained only one trial. For gastric cancer, there is high uncertainty about the effect of CRS + HIPEC + systemic chemotherapy. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, CRS + HIPEC + systemic chemotherapy probably decreases all‐cause mortality compared to CRS + systemic chemotherapy. For colorectal cancer, CRS + HIPEC + systemic chemotherapy probably results in little to no difference in all‐cause mortality and may increase the serious adverse events proportions compared to CRS +/− systemic chemotherapy, but probably decreases all‐cause mortality compared to fluorouracil‐based systemic chemotherapy alone. Interpretation: The role of CRS + HIPEC in gastric peritoneal metastases is uncertain. CRS + HIPEC should be standard of care in women with stage III or greater epithelial ovarian cancer undergoing interval CRS. CRS + systemic chemotherapy should be standard of care for people with colorectal peritoneal metastases, with HIPEC given only as part of a RCT focusing on subgroups and regimes. PROSPERO Registration: CRD42019130504. [ABSTRACT FROM AUTHOR]

Simple Summary: Routine resection of surgical scars could prevent scar recurrences after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases and pseudomyxoma peritonei. However, there is no clear evidence for resecting all surgical scars, irrespective of macroscopic suspicion of scar metastases, and scar resection is associated with wound complications. Careful macroscopic assessment of surgical scars is needed to avoid routine scar resection. This study aimed to analyze the correlation between macroscopically suspected and microscopically confirmed scar metastases, and to analyze the prognostic impact of not undergoing routine scar resection. This study showed that occult scar metastases were uncommon and patients not undergoing routine scar resection did not have worse recurrence-free or overall survival compared with those undergoing scar resection. Therefore, macroscopically benign-appearing scars can be left without resection, though resection should be performed in case of uncertainty. 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. [ABSTRACT FROM AUTHOR]

PurposeThis was a review of circulating tumor DNA (ctDNA) in patients with peritoneal metastases from colorectal cancer.MethodsWe searched the PubMed database for studies reporting detection of ctDNA in patients with colorectal cancer (CRC) and with peritoneal metastases (PM) from colorectal cancer (CRPM). We extracted data on the population included, number of subjects, study design, type of ctDNA assay used and schedule, and the major findings from these publications.ResultsWe identified 13 studies for review investigating ctDNA, using a variety of ctDNA assays, among 1787 patients with CRC without PM, as well as four eligible published and one unpublished (in press) studies, which included 255 patients with PM from any primary site and 61 patients with CRPM. Among the 13 studies investigating ctDNA among CRC without PM, posttreatment surveillance ctDNA was associated with recurrence and was generally more sensitive than imaging or tumor markers. Among the five studies including patients with PM, ctDNA was not universally able to detect the presence of PM, but when present, ctDNA predicted worse outcomes.ConclusionCirculating-tumor DNA is a potentially useful surveillance tool for patients with CRC. However, the sensitivity of ctDNA to detect CRPM is variable and warrants further inquiry.

Background: Programmed death-ligand 1 (PD-L1) expression serves as a predictive biomarker for response to immune checkpoint inhibitors (ICIs) in metastatic gastroesophageal adenocarcinoma (mGEA). The peritoneum is one of the most common metastatic sites and is associated with a poor prognosis and apparently lower clinical efficacy of ICIs. Patients and methods: We investigated the heterogeneity of PD-L1 expression in mGEA by examining its concordance between primary tumors and matched peritoneal metastases (PMs), and before and after systemic treatment. PD-L1 expression was assessed using combined positive score (CPS) by immunohistochemistry with VENTANA PD-L1 (SP263) assays on formalin-fixed paraffin-embedded tumor tissues. Results were reported using CPS cut-offs of 1 and 5. Results: Twenty-two primary tumor and matched PM specimens from patients with mGEA were analyzed. The concordance of PD-L1 CPS was 54.5% with a CPS cut-off of 1 and 72.7% with a CPS cut-off of 5, highlighting spatial heterogeneity. Notably, none of the PD-L1-positive primary tumor samples tested positive in the matched PM specimens using the CPS ≥5 cut-off. Potential temporal heterogeneity of PD-L1 expression related to chemo(immuno)therapy administration was also observed, with a 55.6% concordance rate using the CPS ≥5 cut-off. Conclusions: PD-L1 expression in PMs from mGEA is characterized by both spatial and potentially temporal heterogeneity, with the variability being more pronounced at lower CPS cut-off values. This variability complicates its role as a predictive biomarker for ICI outcomes. The high intrapatient discordance rate in PD-L1 CPS expression between positive primary tumor samples and matched PM specimens suggests that peritoneal specimens should not be used as the only source for PD-L1 assessment if representative tissue from other disease sites is available.

Background We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost–utility analysis. Methods We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost–utility analysis using methods recommended by The National Institute for Health and Care Excellence. Results The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons. Limitations We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges. Conclusions In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation). Future work More randomised controlled trials are necessary. Study registration This study is registered as PROSPERO CRD42019130504. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information. Plain language summary What was the question? Cancers of the bowel, ovary or stomach can spread to the lining of the abdomen (‘peritoneal metastases’). Chemotherapy (the use of drugs that aim to kill cancer cells) given by injection or tablets (‘systemic chemotherapy’) is one of the main treatment options. There is uncertainty about whether adding cytoreductive surgery (cytoreductive surgery; an operation to remove the cancer) and ‘hyperthermic intraoperative peritoneal chemotherapy’ (warm chemotherapy delivered into the lining of the abdomen during cytoreductive surgery) are beneficial. What did we do? We reviewed all the information from medical literature published until 14 April 2022, to answer the above uncertainty. What did we find? We found the following from eight trials, including about 1000 participants. In people with peritoneal metastases from bowel cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably does not provide any benefits and increases harm compared to cytoreductive surgery + systemic chemotherapy, while cytoreductive surgery + systemic chemotherapy appears to increase survival compared to systemic chemotherapy alone. There is uncertainty about the best treatment for people with peritoneal metastases from stomach cancer. In women with peritoneal metastases from ovarian cancer who require systemic chemotherapy before cytoreductive surgery to shrink the cancer to allow surgery (‘advanced ovarian cancer’), hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably increases survival compared to cytoreductive surgery + systemic chemotherapy. What does this mean? In people who can withstand a major operation and in whom cancer can be removed, cytoreductive surgery + systemic chemotherapy should be offered to people with peritoneal metastases from bowel cancer, while hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered to women with peritoneal metastases from ‘advanced ovarian cancer’. Uncertainty in treatment continues for gastric cancer. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information. Scientific summary Background There is uncertainty about whether hyperthermic intraoperative peritoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) improves survival and/or quality of life (QoL) compared to CRS or no treatment in addition to systemic chemotherapy in people with peritoneal metastases who can withstand major surgery. Objectives Primary objectives To compare the relative benefits and harms of HIPEC + CRS ± systemic chemotherapy versus CRS ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or stage III or greater epithelial ovarian cancers eligible to undergo HIPEC + CRS by a systematic review and meta-analysis. Secondary objectives To compare the cost-effectiveness of HIPEC + CRS ± systemic chemotherapy versus CRS ± systemic chemotherapy or systemic chemotherapy alone from the NHS and personal social services (PSS) perspective using a model-based cost–utility analysis. Methods We performed a systematic review of literature by searching MEDLINE, EMBASE, Cochrane Library, Science Citation Index, Conference Proceedings Citation Index, as well as trial registers until 14 April 2022. We followed the standard guidance for performing a high-quality systematic review and meta-analysis. We included only randomised controlled trials (RCTs) and assessed the risk of bias using Risk of Bias version 2.0 (ROB 2.0). We were unable to perform an individual participant data (IPD) meta-analysis as planned because of unforeseen circumstances related to coronavirus disease 2019 (COVID-19). This led to trialists who were also clinical researchers being unable to engage for transfer of IPD. We did not foresee that study authors (surgeons) would be sufficiently engaged with providing IPD soon because of the backlog with surgeries and the fatigue induced by COVID-19. Therefore, we performed a meta-analysis based on aggregate data. We calculated the hazard ratio (HR), risk ratio (RR), rate ratio or mean difference (MD) with 95% confidence intervals (CIs) as appropriate. When applicable, we performed meta-analysis using the random-effects model using Review Manager 5.4. We used GRADE guidance to assess the certainty of evidence and determine the strength of recommendations. For the cost-effectiveness analysis, we performed a model-based cost–utility analysis using methods recommended by The National Institute for Health and Care Excellence (NICE). We estimated the costs and quality-adjusted life-years (QALYs) per patient using lifetime horizon. We calculated the incremental net monetary benefit (incremental NMB) for each comparison based on deterministic analysis and probabilistic sensitivity analysis (PSA). We also performed univariate sensitivity analysis and value of information analysis. Results The systematic review included a total of eight RCTs. A total of 955 participants in seven RCTs were included in the quantitative analysis. All comparisons other than those of ovarian cancer contained only one trial. For colorectal cancer, HIPEC + CRS + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% in HIPEC + CRS + systemic chemotherapy vs. 60.6% in CRS + systemic chemotherapy; median follow-up 64 months; HR 1.00, 95% CI 0.63 to 1.58; one trial; 265 participants; moderate-certainty evidence) and may increase the number of people who developed serious adverse events compared to CRS +/– systemic chemotherapy (25.6% in HIPEC + CRS + systemic chemotherapy vs. 15.2% in CRS + systemic chemotherapy; RR 1.69, 95% CI 1.03 to 2.77; one trial; 265 participants; low-certainty evidence). HIPEC + CRS + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% in HIPEC + CRS + systemic chemotherapy vs. 60.8% in systemic chemotherapy alone; median follow-up 22 months; HR 0.55, 95% CI 0.32 to 0.95; one trial; 105 participants; moderate-certainty evidence). For gastric cancer, there is high uncertainty about the effect of HIPEC + CRS + systemic chemotherapy versus CRS + systemic chemotherapy on all-cause mortality (effect estimates not presented because of very low-certainty evidence). HIPEC + CRS + systemic chemotherapy probably decreases all-cause mortality compared to systemic chemotherapy (40.8% in HIPEC + CRS + systemic chemotherapy vs. 100% in systemic chemotherapy alone; minimum follow-up 24 months; HR 0.40, 95% CI 0.30 to 0.52; one trial; 17 participants; moderate-certainty evidence). For stage III or greater epithelial ovarian cancer requiring interval CRS, HIPEC + CRS + systemic chemotherapy probably decreases all-cause mortality compared to CRS + systemic chemotherapy (46.3% in HIPEC + CRS + systemic chemotherapy vs. 57.4% in CRS + systemic chemotherapy; median follow-up 32–70 months; HR 0.73, 95% CI 0.57 to 0.93; three trials; 500 participants; moderate-certainty evidence). It may result in little to no difference in health-related quality of life (HRQoL) (MD 4.85, 95% CI −7.74 to 17.44; one trial; 71 participants; moderate-certainty evidence) or number of people who developed serious adverse events compared to CRS + systemic chemotherapy (26.7% in HIPEC + CRS + systemic chemotherapy vs. 25.2% in CRS + systemic chemotherapy; RR 1.06, 95% CI 0.73 to 1.54; two trials; 316 participants; moderate-certainty evidence), although it probably increases the number of serious adverse events per participant compared to CRS + systemic chemotherapy (41.4 events per 100 participants in HIPEC + CRS + systemic chemotherapy vs. 32.6 events per 100 participants in CRS + systemic chemotherapy; rate ratio 1.27, 95% CI 1.09 to 1.49; one trial; 184 participants; moderate-certainty evidence). The cost-effectiveness analysis included the five comparisons described above: HIPEC + CRS + systemic chemotherapy versus CRS + systemic chemotherapy for each of the colorectal, gastric and ovarian cancers and HIPEC + CRS + systemic chemotherapy versus systemic chemotherapy alone for each of the colorectal and gastric cancers. In people with colorectal peritoneal metastases, the incremental NMBs at willingness to pay (WTP) of £20,000 and £30,000 were −£6162.83 and −£6164.19, respectively, indicating that HIPEC + CRS + systemic chemotherapy was not cost-effective compared to CRS + systemic chemotherapy in NHS. The likelihood of HIPEC + CRS + systemic chemotherapy being cost-effective compared to CRS + systemic chemotherapy was 46.5% and 47.6% at WTP of £20,000 and £30,000, respectively. In the same group of people, the incremental NMBs at WTP of £20,000 and £30,000 were £107,909.46 and £167,621.58, respectively, indicating that HIPEC + CRS + systemic chemotherapy may be cost-effective compared to systemic chemotherapy alone in NHS. The likelihood of HIPEC + CRS + systemic chemotherapy being cost-effective compared to systemic chemotherapy alone was 89.3% and 90.3% at WTP of £20,000 and £30,000, respectively. In people with gastric peritoneal metastases, the incremental NMBs at WTP of £20,000 and £30,000 were £14,174.73 and £22,955.89, respectively, for HIPEC + CRS + systemic chemotherapy versus CRS + systemic chemotherapy and £81,796.38 and £127,768.23, respectively, for HIPEC + CRS + systemic chemotherapy versus systemic chemotherapy, indicating that HIPEC + CRS + systemic chemotherapy may be cost-effective compared to CRS + systemic chemotherapy or systemic chemotherapy alone in NHS. The likelihood of HIPEC + CRS + systemic chemotherapy being cost-effective ranged between 60% and 70% for the different comparisons and different thresholds. In women with grade III or greater epithelial ovarian cancer requiring interval CRS, the incremental NMBs at WTP of £20,000 and £30,000 were £46,761.81 and £71,938.23, respectively, indicating that HIPEC + CRS + systemic chemotherapy was cost-effective compared to CRS +systemic chemotherapy in NHS. The likelihood of HIPEC + CRS + systemic chemotherapy being cost-effective compared to CRS + systemic chemotherapy was 71.9% and 72.4% at WTP of £20,000 and £30,000, respectively. The value of information analysis indicated that the expected value of perfect information (EVPI) ranged between £3 and £53 million for the different cancer types (when estimation was possible) for WTP of £20,000 and £30,000. Discussion and conclusions Limitations of the review We were unable to obtain IPD as planned. IPD would have allowed us to refine our effect estimates for subgroups of people with peritoneal metastases from colorectal, gastric or stage III or greater epithelial ovarian cancer. It is difficult to estimate whether our conclusions would have changed if we had IPD; however, our systematic review and meta-analysis support similar conclusions as the trial authors, suggesting that the impact of IPD may not be major enough to warrant an IPD once the health services have recovered from the impact of COVID-19. We estimated the HR for survival for gastric cancer trials from Kaplan–Meier curves. This might have introduced bias. However, because of the small number of participants and the estimations that we have performed to calculate the effect estimates, we have concluded that there is uncertainty in the benefit of HIPEC + CRS + systemic chemotherapy in gastric cancers. Because of the paucity of trials under each comparison, evidence from new RCTs of low risk of bias may change our recommendations. There are concerns regarding the clinical recommendations for people with colorectal peritoneal metastases based on the PRODIGE-7 trial. We have discussed in detail the different concerns raised and why these concerns should not be used as a justification for not basing clinical practice on PRODIGE-7 trial (in the full article). In summary, we based our clinical practice recommendations for colorectal peritoneal metastases on PRODIGE-7 trial because the trial was a low risk of bias trial for the comparison of HIPEC + CRS + systemic chemotherapy versus CRS + systemic chemotherapy. An appropriate analysis was used to analyse trial data, and there was no other trial of low of bias comparing HIPEC + CRS + systemic chemotherapy versus CRS + systemic chemotherapy. While the CRS + systemic chemotherapy was not directly compared with systemic chemotherapy alone, we recommended CRS + systemic chemotherapy in people with colorectal peritoneal metastases because of the lack of any ‘systemic chemotherapy alone’ treatments that provide equivalent median survival as that observed in the control arm (CRS + systemic chemotherapy) in the PRODIGE-7 trial. Because of the difficulties in estimating the Peritoneal Cancer Index (PCI) during surgery, we have not recommended HIPEC + CRS + systemic chemotherapy even for the subset of patients with PCI 11–15, but this exploratory subgroup analysis can guide future research. We have not based our recommendations on non-randomised studies, as we did not find any non-randomised study in which similar participants with colorectal peritoneal metastases underwent HIPEC + CRS + systemic chemotherapy versus CRS + systemic chemotherapy or systemic chemotherapy alone. CRS + systemic chemotherapy provides equivalent median survival of 41 months as HIPEC + CRS + systemic chemotherapy. When there is an existing, less invasive treatment that provides equivalent survival, it can hardly be considered life-threatening to warrant recommendations based on low-or very low-certainty evidence. Recommendations for clinical practice In people with peritoneal metastases from colorectal cancer, based on the results of PRODIGE-7 trial, HIPEC + CRS + systemic chemotherapy probably results in little to no difference in all-cause mortality or progression-free survival and results in increased complications compared to CRS + systemic chemotherapy. Therefore, HIPEC based on oxaliplatin regimen used in PRODIGE-7 trial + CRS + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). Because of the lack of reliability of preoperative or perioperative PCI, the lack of pre-PRODIGE-7 trial standard classification of PCI into PCI 15 and pre-defined subgroup analysis based on the PCI classification, HIPEC based on oxaliplatin regimen used in PRODIGE-7 trial + CRS + systemic chemotherapy cannot be recommended for any subgroups. Because of the median survival observed in the CRS + systemic chemotherapy arm of PRODIGE-7 trial (41 months) and the poor survival observed in people with disseminated colorectal peritoneal metastases (

Abstract Background Peritoneal metastases from colorectal cancer (CRCPM) are related to poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been reported to improve survival, but peritoneal recurrence rates are still high and there is no consensus on the drug of choice for HIPEC. The aim of this study was to use patient derived organoids (PDO) to build a relevant CRCPM model to improve HIPEC efficacy in a comprehensive bench-to-bedside strategy. Methods Oxaliplatin (L-OHP), cisplatin (CDDP), mitomycin-c (MMC) and doxorubicin (DOX) were used to mimic HIPEC on twelve PDO lines derived from twelve CRCPM patients, using clinically relevant concentrations. After chemotherapeutic interventions, cell viability was assessed with a luminescent assay, and the obtained dose–response curves were used to determine the half-maximal inhibitory concentrations. Also, induction of apoptosis by different HIPEC interventions on PDOs was studied by evaluating CASPASE3 cleavage. Results Response to drug treatments varied considerably among PDOs. The two schemes with better response at clinically relevant concentrations included MMC alone or combined with CDDP. L-OHP showed relative efficacy only when administered at low concentrations over a long perfusion period. PDOs showed that the short course/high dose L-OHP scheme did not appear to be an effective choice for HIPEC in CRCPM. HIPEC administered under hyperthermia conditions enhanced the effect of chemotherapy drugs against cancer cells, affecting PDO viability and apoptosis. Finally, PDO co-cultured with cancer-associated fibroblast impacted HIPEC treatments by increasing PDO viability and reducing CASPASES activity. Conclusions Our study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM.

Regorafenib is a multikinase inhibitor approved for treatment of patients with metastatic Colo-Rectal Cancer (mCRC) and Gastro-Intestinal Stromal Tumor (GIST) progression after the administration of other tyrosine-kinase inhibitors such as imatinib and sunitinib.Only a handful of severe side effects such as intestinal perforations and fistulas have been described in the literature in patients undergoing multikinase inhibitor treatment. We report a case of a patient with peritoneal mCRC who experienced an intestinal perforation during the administration of Regorafenib and review the literature. A 48-year-old man with previously resected sigmoid colon cancer and peritoneal metastatic disease under Regorafenib treatment presented to our Emergency Department with severe abdominal pain and asthenia. Abdominal X-ray and contrast-enhanced computed tomography examination revealed an intestinal perforation. The patient underwent emergency surgery which demonstrated acute diffuse peritonitis, necrosis, and perforation of a distal ileal loop affected by peritoneal metastatic disease. The necrosis of peritoneal implants on bowel walls could be regarded as a potential factor leading to intestinal perforation in metastatic colorectal cancer patients undergoing Regorafenib treatment complaining of severe abdominal pain and asthenia.Surgeons, radiologists and oncologists should always keep in mind this rare adverse event during Regorafenib administration. Appropriate diagnostic tests and treatments should be carried out.

Abstract Background Colorectal peritoneal metastases (CRPM) affects 15% of patients at initial colorectal cancer diagnosis. Neoadjuvant chemotherapy (NAC) prior to cytoreductive surgery (CRS) has been demonstrated to be a safe and feasible option, however there is limited data describing its efficacy in advanced peritoneal disease. This study evaluated the effect of NAC on survival in patients with high volume CRPM undergoing CRS with or without HIPEC. Methods A retrospective review of all patients who underwent CRS with or without HIPEC for CRPM from 2004 to 2019 at our institution was performed. The cohort was divided based on peritoneal carcinomatosis index (PCI) at surgery: Low Volume (PCI ≤ 16) and High Volume (PCI > 16). Results A total of 326 patients underwent CRS with HIPEC for CRPM. There were 39 patients (12%) with High Volume disease, and 15 of these (38%) received NAC. Patients with High Volume disease had significantly longer operating time, lower likelihood of complete macroscopic cytoreduction (CC-0 score), longer intensive care unit length of stay and longer hospital stay compared to Low Volume disease. In High Volume disease, the NAC group had a significantly shorter median survival of 14.4 months compared to 23.8 months in the non-NAC group (p = 0.046). Conclusion Patients with High Volume CRPM achieved good median survival following CRS with HIPEC, which challenges the current PCI threshold for offering CRS. The use of NAC in this cohort did not increase perioperative morbidity but was associated with significantly shorter median survival compared to upfront surgery.

Abstract Background Colorectal peritoneal metastases (CRPM) are present in 10–20% of patients at the time of their initial cancer diagnosis, and affects over 20% of those who develop colorectal cancer recurrence. Cytoreductive surgery (CRS) with HIPEC is firmly established as the optimal surgical treatment, but there is very little known about the benefit of repeat or iterative CRS. The aim of this review is to provide a systematic evaluation of the perioperative complications, survival outcomes and quality of life in patients undergoing repeat CRS with HIPEC for CRPM. Methods A systematic review of PubMed, Ovid MEDLINE, EMBASE, Scopus and Cochrane databases was performed to identify all studies that reported outcomes for repeat CRS with or without HIPEC for CRPM. Results Four hundred and ninety-three manuscripts were screened, and 15 retrospective studies were suitable for inclusion. Sample sizes ranged from 2 to 30 participants and comprised a total of 229 patients. HIPEC was used in all studies, but exact rates were not consistently stated. Perioperative morbidity was reported in four studies, between 16.7% and 37.5%. Nine studies reported mortality rate which was consistently 0%. The median overall survival after repeat CRS ranged from 20 to 62.6 months. No studies provided quality of life metrics. Conclusion Repeat CRS for CRPM has perioperative morbidity and mortality rates comparable to initial CRS, and offers a potential survival benefit in selected patients. There is however limited high-quality data in the literature.

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.

Background: Peritoneal metastases from colorectal cancer (CRCPM) are related to poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been reported to improve survival, but peritoneal recurrence rates are still high and there is no consensus on the drug of choice for HIPEC. The aim of this study was to use patient derived organoids (PDO) to build a relevant CRCPM model to improve HIPEC efficacy in a comprehensive bench-to-bedside strategy. Methods: Oxaliplatin (L-OHP), cisplatin (CDDP), mitomycin-c (MMC) and doxorubicin (DOX) were used to mimic HIPEC on twelve PDO lines derived from twelve CRCPM patients, using clinically relevant concentrations. After chemotherapeutic interventions, cell viability was assessed with a luminescent assay, and the obtained dose–response curves were used to determine the half-maximal inhibitory concentrations. Also, induction of apoptosis by different HIPEC interventions on PDOs was studied by evaluating CASPASE3 cleavage. Results: Response to drug treatments varied considerably among PDOs. The two schemes with better response at clinically relevant concentrations included MMC alone or combined with CDDP. L-OHP showed relative efficacy only when administered at low concentrations over a long perfusion period. PDOs showed that the short course/high dose L-OHP scheme did not appear to be an effective choice for HIPEC in CRCPM. HIPEC administered under hyperthermia conditions enhanced the effect of chemotherapy drugs against cancer cells, affecting PDO viability and apoptosis. Finally, PDO co-cultured with cancer-associated fibroblast impacted HIPEC treatments by increasing PDO viability and reducing CASPASES activity. Conclusions: Our study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM. [ABSTRACT FROM AUTHOR]

Background: Colorectal peritoneal metastases (CRPM) are present in 10–20% of patients at the time of their initial cancer diagnosis, and affects over 20% of those who develop colorectal cancer recurrence. Cytoreductive surgery (CRS) with HIPEC is firmly established as the optimal surgical treatment, but there is very little known about the benefit of repeat or iterative CRS. The aim of this review is to provide a systematic evaluation of the perioperative complications, survival outcomes and quality of life in patients undergoing repeat CRS with HIPEC for CRPM. Methods: A systematic review of PubMed, Ovid MEDLINE, EMBASE, Scopus and Cochrane databases was performed to identify all studies that reported outcomes for repeat CRS with or without HIPEC for CRPM. Results: Four hundred and ninety-three manuscripts were screened, and 15 retrospective studies were suitable for inclusion. Sample sizes ranged from 2 to 30 participants and comprised a total of 229 patients. HIPEC was used in all studies, but exact rates were not consistently stated. Perioperative morbidity was reported in four studies, between 16.7% and 37.5%. Nine studies reported mortality rate which was consistently 0%. The median overall survival after repeat CRS ranged from 20 to 62.6 months. No studies provided quality of life metrics. Conclusion: Repeat CRS for CRPM has perioperative morbidity and mortality rates comparable to initial CRS, and offers a potential survival benefit in selected patients. There is however limited high-quality data in the literature. [ABSTRACT FROM AUTHOR]

Background: Colorectal peritoneal metastases (CRPM) affects 15% of patients at initial colorectal cancer diagnosis. Neoadjuvant chemotherapy (NAC) prior to cytoreductive surgery (CRS) has been demonstrated to be a safe and feasible option, however there is limited data describing its efficacy in advanced peritoneal disease. This study evaluated the effect of NAC on survival in patients with high volume CRPM undergoing CRS with or without HIPEC. Methods: A retrospective review of all patients who underwent CRS with or without HIPEC for CRPM from 2004 to 2019 at our institution was performed. The cohort was divided based on peritoneal carcinomatosis index (PCI) at surgery: Low Volume (PCI ≤ 16) and High Volume (PCI > 16). Results: A total of 326 patients underwent CRS with HIPEC for CRPM. There were 39 patients (12%) with High Volume disease, and 15 of these (38%) received NAC. Patients with High Volume disease had significantly longer operating time, lower likelihood of complete macroscopic cytoreduction (CC-0 score), longer intensive care unit length of stay and longer hospital stay compared to Low Volume disease. In High Volume disease, the NAC group had a significantly shorter median survival of 14.4 months compared to 23.8 months in the non-NAC group (p = 0.046). Conclusion: Patients with High Volume CRPM achieved good median survival following CRS with HIPEC, which challenges the current PCI threshold for offering CRS. The use of NAC in this cohort did not increase perioperative morbidity but was associated with significantly shorter median survival compared to upfront surgery. [ABSTRACT FROM AUTHOR]

A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2TS, MRC1; MS4A4A; CD36; CCL13; CCL18; CCL23; SLC38A6; FGL2; FN1; MAF) and M1 (M1TS, CCR7; IL2RA; CXCL11; CCL19; CXCL10; PLA1A; PTX3) macrophages, and cytolytic T-lymphocytes (CTLTS, GZMA; GZMB; GZMH; GZMM; PRF1). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2TS expression was associated with histological types and later stages. Low M2TS expression was associated with significantly better 5-year OS and DFI. We validated M2TS in prospectively collected peritoneal fluid of a GC patient cohort (n = 28). Single-cell RNA sequencing was used for signature expression in CD68+CD163+ cells and the log-rank test compared OS. GC patients with high M2TS in CD68+CD163+ cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2TS was significantly and independently associated with survival. As an independent predictor of poor survival, M2TS may be prognostic in primary tumors and peritoneal fluid of GC patients. [ABSTRACT FROM AUTHOR]

The aims of this study were to investigate incidence, risk factors and treatment of synchronous or metachronous peritoneal metastases (PM) from gastric cancer and to estimate survival of these patients using population‐based data. Patients diagnosed with gastric cancer in 2015 to 2016 were selected from the Netherlands Cancer Registry. The incidence of synchronous and metachronous PM were calculated. Multivariable regression analyses were performed to identify factors associated with the occurrence of PM. Treatment and survival were compared between patients with synchronous and metachronous PM. Of 2206 patients with gastric cancer, 741 (34%) were diagnosed with PM. Of these, 498 (23%) had synchronous PM. The cumulative incidence of metachronous PM in patients who underwent potentially curative treatment (n = 675) was 22.8% at 3 years. A factor associated with synchronous and metachronous PM was diffuse type histology. Patients diagnosed with synchronous PM more often received systemic treatment than patients with metachronous PM (35% vs 18%, respectively, P <.001). Median overall survival was comparable between synchronous and metachronous PM (3.2 vs 2.3 months, respectively, P =.731). Approximately one third of all patients with gastric cancer are diagnosed with PM, either at primary diagnosis or during 3‐year follow‐up after potentially curative treatment. Patients with metachronous PM less often received systemic treatment than those with synchronous PM but survival was comparable between both groups. Future trials are warranted to detect gastric cancer at an earlier stage and to examine strategies that lower the risk of peritoneal dissemination. Also, specific treatment options for patients with gastric PM should be further investigated. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with advanced gastric cancer (AGC) often discontinue treatment when peritoneal metastases progress, particularly during second- or third-line chemotherapy. To prevent serious complications like bowel obstruction or increased ascites burden, it is crucial to identify predictors of peritoneal metastases before they occur. In this study, serum carbohydrate antigen 125 (CA125) concentrations were found to be associated with increased ascites burden in patients with AGC and served as a prognostic factor. Moreover, CA125 kinetics, measured at a median interval of 28 days after initiating taxane-plus-ramucirumab treatment, were found to be associated with the ascites response. Furthermore, an increase in CA125 concentration exceeding 0.0067% per day, as determined by receiver operating characteristic curve analysis, predicted the progression of peritoneal metastases. Thus, monitoring CA125 kinetics is vital for predicting the progression of peritoneal metastases and can help determine the optimal timing for subsequent chemotherapy. Currently, no established marker exists for predicting peritoneal metastasis progression during chemotherapy, although they are major interruptive factors in sequential chemotherapy in patients with advanced gastric cancer (AGC). This multicenter retrospective study was conducted from June 2015 to July 2019, analyzing 73 patients with AGC who underwent taxane-plus-ramucirumab (TAX/RAM) therapy and had their serum carbohydrate antigen 125 (CA125) concentrations measured. Of 31 patients with elevated CA125 levels above a cutoff of 35 U/mL, 25 (80.6%) had peritoneal metastasis. The CA125 concentrations before TAX/RAM treatment were associated with ascites burden. The overall survival was significantly shorter in the CA125-elevated group. CA125 kinetics, measured at a median of 28 days after chemotherapy, were associated with the ascites response (complete or partial response: −1.86%/day; stable disease: 0.28%/day; progressive disease: 2.33%/day). Progression-free survival in the CA125-increased group, defined by an increase of 0.0067%/day using receiver operating characteristic curve analysis, was significantly poorer among patients with peritoneal metastases. In conclusion, this study highlights that CA125 kinetics can serve as an early predictor for the progression of peritoneal metastasis during TAX/RAM treatment. [ABSTRACT FROM AUTHOR]

Purpose: This was a review of circulating tumor DNA (ctDNA) in patients with peritoneal metastases from colorectal cancer. Methods: We searched the PubMed database for studies reporting detection of ctDNA in patients with colorectal cancer (CRC) and with peritoneal metastases (PM) from colorectal cancer (CRPM). We extracted data on the population included, number of subjects, study design, type of ctDNA assay used and schedule, and the major findings from these publications. Results: We identified 13 studies for review investigating ctDNA, using a variety of ctDNA assays, among 1787 patients with CRC without PM, as well as four eligible published and one unpublished (in press) studies, which included 255 patients with PM from any primary site and 61 patients with CRPM. Among the 13 studies investigating ctDNA among CRC without PM, posttreatment surveillance ctDNA was associated with recurrence and was generally more sensitive than imaging or tumor markers. Among the five studies including patients with PM, ctDNA was not universally able to detect the presence of PM, but when present, ctDNA predicted worse outcomes. Conclusion: Circulating-tumor DNA is a potentially useful surveillance tool for patients with CRC. However, the sensitivity of ctDNA to detect CRPM is variable and warrants further inquiry. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer with peritoneal metastases can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Treatment may result in biopsychosocial late effects (LEs). We explored the frequency and severity of the following biopsychosocial LEs: anxiety, depression, fear of cancer recurrence (FCR), insomnia, fatigue, cognitive impairment, and pain, and evaluated their impact on quality of life (QoL). Method: This was a national prospective cohort study screening for LEs during the period January 2021–May 2023. Patients completed the following questionnaires: General Anxiety Disorder-7, Patient Health Questionnaire-9, FCR Inventory-Short Form, Insomnia Severity Index, Functional Assessment of Chronic Illness Therapy-Fatigue, cognitive impairment (six items from the European Organisation for Research and Treatment of Cancer Item Library), and the Rectal Cancer Pain Score. Preregistration was completed at ClinicalTrials.gov (NCT04956107). Result: In total, 99 patients were included. The mean age was 61 years and 57% were women. At 3 months after surgery, the frequent LEs were fatigue (72%), FCR (58%), and pain (48%), and at 12 months after surgery, the frequent LEs were FCR (65%), fatigue (40%), and insomnia (33%). More than half of the patients (54%) reported at least two LEs after 12 months. Patients with moderate-to-severe LEs reported a lower QoL than patients with no/mild LEs. Patients with no/mild LEs had a similar QoL as the Danish norm population. Conclusion: Biopsychosocial LEs were prevalent. The QoL of patients reporting LEs in the worst severity categories was negatively impacted. Screening and treatment for these LEs should be a focus in cancer survivor follow-up. [ABSTRACT FROM AUTHOR]

Background: Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population. This study investigates to what extent systemic anti-cancer therapy crosses the peritoneal barrier. Methods: In a Phase I study, eighteen patients received systemic oxaliplatin, 5-FU, and bevacizumab. Plasma and peritoneal fluid samples were collected to measure drug concentrations. A non-compartmental analysis determined the Area Under the Curve (AUC) for oxaliplatin and 5-FU in both matrices. Intraperitoneal (IP) and intravenous (IV) exposure ratios were calculated, along with the bevacizumab concentration IP/IV ratio. The relationship between tumour load and IP/IV ratios and the correlation between the IP/IV ratios of different treatments were assessed statistically. Results: A total of 438 5-FU samples and 578 oxaliplatin samples were analysed in plasma and peritoneal fluid. Bevacizumab was quantified with 17 measurements in plasma and 15 measurements IP. Median IP/IV ratios were 0.143, 0.352 and 0.085 for 5-FU, oxaliplatin and bevacizumab, respectively. Oxaliplatin exhibited a longer IP half-life than 5-FU. A correlation was found between oxaliplatin and bevacizumab IP/IV ratios (R=0.69, p=0.01). No statistical correlations were found between the other investigated drugs. Conclusions: Our findings indicate that only a small percentage of systemically administered anti-cancer treatment reaches the IP cavity, questioning their efficacy against PM. This strengthens the hypothesis for repeated intraperitoneal chemotherapy to reach adequate anti-cancer drug levels.

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I–II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien–Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I–II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien–Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices. [ABSTRACT FROM AUTHOR]

Background: Peritoneal carcinomatosis is a particularly rare presentation of prostate cancer. Here we report a rare clinical case of surgically identified peritoneal carcinomatosis at the time of a planned robotic prostatectomy in a patient with a history of prostatic urethral lift procedure. Case presentation: A 72-year-old man, with a history of urinary retention managed with tamsulosin, presented to his local urologist. Prostatic urethral lift procedures were performed for symptom management. After a definitive uptrend in his prostate-specific antigen (PSA) values, a biopsy was obtained, which demonstrated prostate adenocarcinoma. On presurgical multidisciplinary review, it was presumed that he had very high-risk localized prostate cancer. However, upon initiation of robotically assisted laparoscopic radical prostatectomy (RALP), he was noted to have numerous punctate white plaques on the peritoneum; biopsy of these lesions confirmed metastatic disease--for which the patient was starting on triple therapy per the PEACE-1 trial. The PSA level responded appropriately, decreasing from 16.8 to 0.08. Genetic testing was performed and returned negative for any clinically significant mutations. Conclusion: Our patient, diagnosed with peritoneal carcinomatosis during a planned RALP, highlights the importance of vigilant laparoscopic exam prior to this prostatectomy. Multidisciplinary discussion is crucial for individualized and optimal treatment planning. [ABSTRACT FROM AUTHOR]

Simple Summary: The concept of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy perfusion for the treatment of colorectal cancer peritoneal metastases has been debated based on the results of recent controlled trials. In this review, we describe the development of this "package" treatment and discuss various aspects of the selection and indications, as well as future fields of research. Peritoneal metastases (PM) are observed in approximately 8% of patients diagnosed with colorectal cancer, either synchronously or metachronously during follow-up. PM often manifests as the sole site of metastasis. PM is associated with a poor prognosis and typically shows resistance to systemic chemotherapy. Consequently, there has been a search for alternative treatment strategies. This review focuses on the global evolution of the combined approach involving cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of PM. It encompasses accepted clinical guidelines, principles for patient selection, surgical and physiological considerations, biomarkers, pharmacological protocols, and treatment outcomes. Additionally, it integrates the relevant literature and findings from previous studies. The role of CRS and HIPEC, in conjunction with other therapies such as neoadjuvant and adjuvant chemotherapy, is discussed, along with the management of patients presenting with oligometastatic disease. Furthermore, potential avenues for future development in this field are explored. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have demonstrated their impact on disease-free survival (DFS) and overall survival (OS) of patients with peritoneal metastases (PM). However, prior literature lacks evidence regarding any follow-up beyond 5 years. In this study, we analyse long-term OS and DFS (more than 10 years of follow-up) of patients undergoing CRS + HIPEC in a specialized unit. We conducted a retrospective study that included only patients who underwent CRS + HIPEC from January 2001 to May 2012. Data collection was conducted by reviewing medical records and telephone calls to patients or relatives. A total of 86 patients were included. The mean PCI was nine (range 0–39) and complete cytoreduction (CC-0) was reached in 80% of patients. Postoperative complications Clavien–Dindo III-IV occurred in 27.9% of patients and the 30-day mortality rate was 2.3%. After 10 years of actual follow-up, OS was 33.7% and DFS was 31.4%. Considering the historical context in which the standard of care for patients with PM was palliation, the results obtained show that CRS + HIPEC was a valid option, with morbimortality comparable to other major abdominal surgeries and encouraging survival results, since, after 10 years of follow-up, almost one-third of patients are still alive and disease-free. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Distant metastases are frequent in head and neck squamous cell carcinomas (HNSCC), but they are limited to some organs like lungs, bone, mediastinum, liver and brain. Peritoneal metastases (PMs) from HNSCC are extremely rare. A 28-year-old chronic smoker and alcoholic was diagnosed with squamous cell carcinoma of oropharynx. Patient was admitted and was given six cycles of concurrent chemo and radiotherapy (CCRT) and was discharged. Two months later, he presented with abdominal pain and lump. Contrast-enhanced CT revealed ascites, peritoneal implants and subcutaneous deposit which were proved to be metastases by histopathology. The present case is the seventh reported case of PM from HNSCC. • Patients of HNSCC shall be screened for distant metastases. • Differential diagnosis of HNSCC needs consideration when encountered with peritoneal metastases. • Research is required to understand the basis of PM in HNSCC while on CCRT to suggest management modifications. [ABSTRACT FROM AUTHOR]

Peritoneal metastases (PM) occur when cancer cells spread inside the abdominal cavity and entail an advanced stage of colorectal cancer (CRC). Prognosis, which is poor, correlates highly with tumour burden, as measured by the peritoneal cancer index (PCI). Cytoreductive surgery (CRS) in specialized centres should be offered especially to patients with a low to moderate PCI when complete resection is expected. The presence of resectable metastatic disease in other organs is not a contraindication in well-selected patients. Although several retrospective and small prospective studies have suggested a survival benefit of adding hyperthermic intraperitoneal chemotherapy (HIPEC) to CRS, the recently published phase III studies PRODIGE-7 in CRC patients with PM, and COLOPEC and PROPHYLOCHIP in resected CRC with high-risk of PM, failed to show any survival advantage of this strategy using oxaliplatin in a 30-min perfusion. Final results from ongoing randomized phase III trials testing CRS plus HIPEC based on mitomycin C (MMC) are awaited with interest. In this article, a group of experts selected by the Spanish Group for the Treatment of Digestive Tumours (TTD) and the Spanish Group of Peritoneal Oncologic Surgery (GECOP), which is part of the Spanish Society of Surgical Oncology (SEOQ), reviewed the role of HIPEC plus CRS in CRC patients with PM. As a result, a series of recommendations to optimize the management of these patients is proposed. [ABSTRACT FROM AUTHOR]

Abstract Background Gastric cancer (GC) remains among the most common and most lethal cancers worldwide. Peritoneum is the most common site for distant dissemination. Standard treatment for GC peritoneal metastases (PM) is a systemic therapy, but treatment outcomes remain very poor, with median overall survival ranging between 3-9 months. Thus, novel treatment methods are necessary. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is the most novel technique for intraperitoneal chemotherapy. Some preliminary data suggest PIPAC can achieve improved long-term outcomes in patients with GC PM, especially when used in combination with systemic chemotherapy. However, there is a lack of data from well-design prospective studies that would confirm the efficacy of PIPAC and systemic therapy combination for first-line treatment. Methods This study is an investigator-initiated single-arm, phase II trial to investigate the efficacy of PIPAC combined with systemic FOLFOX (5-fluorouracil, oxaliplatin, leucovorin) as a first-line treatment for GC PM. The study is conducted in 2 specialized GC treatment centers in Lithuania. It enrolls GC patients with histologically confirmed PM without prior treatment. The treatment protocol consists of PIPAC with cisplatin (10.5 mg/m2 body surface in 150 mL NaCl 0.9%) and doxorubicin (2.1 mg/m2 in 50 mL NaCl 0.9%) followed by 2 cycles of FOLFOX every 6–7 weeks. In total 3 PIPACs and 6 cycles of FOLFOX will be utilized. The primary outcome of the study is the objective response rate (ORR) according to RECIST v. 1.1 criteria (Eisenhauer et al., Eur J Cancer 45:228–47) in a CT scan performed 7 days after the 4th cycle of FOLFOX. Secondary outcomes include ORR after all experimental treatment, PIPAC characteristics, postoperative morbidity, histological and biochemical response, ascites volume, quality of life, overall survival, and toxicity. Discussion This study aims to assess PIPAC and FOLFOX combination efficacy for previously untreated GC patients with PM. Trial registration NCT05644249. Registered on December 9, 2022.

Abstract Background Obesity is a major global health problem and an important risk factor for colorectal cancer (CRC) is increased body weight. Obesity plays a role in the peritoneal dissemination of cancer; however, it is unclear whether this also applies for peritoneal dissemination of CRC. The purpose of this study was to provide insight in the role of obesity on the peritoneal dissemination of colorectal cancer. Methods Of all patients diagnosed with CRC in the Netherlands in the first half of 2015, follow-up data was completed in 2019. Weight at time of primary diagnosis was categorized as underweight, normal weight, overweight, or obese. Logistic regression modelling was used to assess the association between weight and the presence of synchronous colorectal peritoneal metastases (CPM), and Cox regression modelling was used to assess the association between weight and metachronous CPM. Patient and tumor characteristics were taken into account. The analyses were adjusted for tumor stage, nodal stage, tumor location, and tumor histology. Results In total, 6436 patients were included in this study. Two-hundred ninety-three (4.6%) patients presented with synchronous CPM at the time of primary diagnosis, while another 278 (5.1%) patients developed metachronous CPM after a median time of 16.5 months. Univariable and multivariable logistic regression modelling did not identify an effect of weight on the presence of synchronous CPM. Neither underweight (odds ratio [OR] 1.10, 95% CI 0.48–2.54), nor overweight (OR 0.96, 95% CI 0.71–1.29), or obesity (OR 0.84, 95% CI 0.56–1.26) was either positively or negatively associated with the presence of synchronous peritoneal metastases as compared to normal weight. Univariable and multivariable Cox regression modelling did not identify an effect of weight on the development of metachronous CPM. Neither underweight (HR 0.162, 95% CI 0.02–1.16), nor overweight (HR 1.07, 95% CI 0.82–1.39), or obesity (HR 1.02, 95% CI 0.73–1.16) was either positively or negatively associated with the presence of synchronous peritoneal metastases as compared to normal weight. Conclusion CRC patients who are overweight or obese are not more at risk for the presence of synchronous CPM nor development of metachronous CPM than their normal-weight counterparts.

This is the first UK trial of pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for colorectal cancer peritoneal metastases. This trial aimed to assess the impact of PIPAC in combination with standard of care systemic treatment on: progression free survival (PFS); quality of life (QoL); and short-term complications. In addition, this trial set out to demonstrate that PIPAC can be performed safely in operating theatres within a National Health Service (NHS) setting.

BackgroundPrior studies attempting to identify disparities in the care of patients with appendiceal (AC) or colorectal cancer (CRC) with peritoneal metastasis (PM) are limited to single-institution, highly selected patient populations. This observational cohort study sought to identify factors associated with specialty care for Medicare beneficiaries with AC/CRC-PM.Materials and methodsPatients >65 years old in the United States diagnosed with AC/CRC and isolated PM were identified within the Medicare Standard Analytic File (2013-2017). Mixed-effects analyses assessed patient factors associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and outpatient consultation with a peritoneal surface malignancy (PSM) surgeon, and Cox proportional-hazards analysis compared 3-year overall survival (OS) between patients receiving CRS/HIPEC versus systemic therapy alone.ResultsAmong 7,653 patients, only 250 (3.3%) underwent CRS/HIPEC. Among those individuals who did not undergo CRS/HIPEC (N=7,403), only 475 (6.4%) had outpatient consultation with a PSM surgeon. Patient factors independently associated with lower odds of CRS/HIPEC and PSM surgery consultation included older age, greater comorbidity burden, higher social vulnerability index, and further distance from a PSM center (p

Multimodal treatment in peritoneal metastases (PM) from colorectal neoplasms may improve overall survival (OS). In this study, we reported our experience in using cytoreductive surgery (CRS) combined with intraperitoneal chemohyperthermia (HIPEC) for the treatment of peritoneal metastases (PM) from colorectal neoplasms. The first aim was to evaluate the overall survival of these patients. Furthermore, using the results of the Prodige 7 Trial and incorporating them with the entropy balance statistical tool, we generated a pseudopopulation on which to test the use of CRS alone. We performed a retrospective analysis based on a prospective database of all 55 patients treated with CRS + HIPEC between March 2004 and January 2023. The median OS was 47 months, with 1-, 3- and 5-year survival rates of 90.8%, 58.7% and 42.7%, respectively. There was no significant difference in the data in the pseudogroup generated with entropy balance. This finding confirms the critical role of complete cytoreduction in achieving the best OS for patients with PM. PCI > 6 seems to be the most important prognostic factor influencing OS. At present, CRS + HIPEC seems to be the therapeutic strategy that guarantees the best results in terms of OS for patients with relatively low PCI and in whom a CCS ≤ 1 can be achieved.

Abstract Background Small bowel cancer (SBC) is a rare malignancy that is often diagnosed at an advanced stage. Palliative chemotherapy is the standard treatment for patients with metastatic SBC. The relevant literature on conversion surgery in patients who have responded favorably to chemotherapy is limited. Case presentation A 64-year-old man was diagnosed with jejunal carcinoma with multiple peritoneal metastases. After implanting an expandable metallic stent at the primary site, the patient underwent 6 months of FOLFOX therapy, resulting in a clinical complete response. Chemotherapy was continued, and four years after the initiation of therapy, the patient showed no evidence of disease progression. Nevertheless, anemia of continuous minor hemorrhages from the stent site and general malaise of chemotherapy got progressively worse during treatment. After confirming negative ascites cytology and the absence of peritoneal metastasis via staging laparoscopy, the patient underwent partial jejunectomy. Pathologically, no residual tumor was detected in the resected specimen. The postoperative course was uneventful, and the patient remained free of recurrence for 30 months after surgery without chemotherapy. Conclusion Although infrequent, conversion surgery may be a valid therapeutic option for selected cases of SBC with peritoneal metastasis.

Peritoneal metastases (PM) and liver metastases (LM) are present simultaneously in up to 2 % of patients at the time of their colorectal cancer (CRC) diagnosis. Curatively intended treatment includes cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with LM resection. A less invasive treatment for LM is ablation. We aimed to estimate overall survival (OS), disease-free survival (DFS) and postoperative data in patients managed simultaneously with CRS, HIPEC and radiofrequency ablation (RFA) as first choice.

BackgroundPeritoneal carcinomatosis is a particularly rare presentation of prostate cancer. Here we report a rare clinical case of surgically identified peritoneal carcinomatosis at the time of a planned robotic prostatectomy in a patient with a history of prostatic urethral lift procedure.Case presentationA 72-year-old man, with a history of urinary retention managed with tamsulosin, presented to his local urologist. Prostatic urethral lift procedures were performed for symptom management. After a definitive uptrend in his prostate-specific antigen (PSA) values, a biopsy was obtained, which demonstrated prostate adenocarcinoma. On presurgical multidisciplinary review, it was presumed that he had very high-risk localized prostate cancer. However, upon initiation of robotically assisted laparoscopic radical prostatectomy (RALP), he was noted to have numerous punctate white plaques on the peritoneum; biopsy of these lesions confirmed metastatic disease—for which the patient was starting on triple therapy per the PEACE-1 trial. The PSA level responded appropriately, decreasing from 16.8 to 0.08. Genetic testing was performed and returned negative for any clinically significant mutations.ConclusionOur patient, diagnosed with peritoneal carcinomatosis during a planned RALP, highlights the importance of vigilant laparoscopic exam prior to this prostatectomy. Multidisciplinary discussion is crucial for individualized and optimal treatment planning.

Gastric cancer peritoneal metastases (GCPM) is a leading cause of GC‐related death. Early detection of GCPM is critical for improving the prognosis of advanced GC. Differentially expressed genes (DEGs) were identified in the GSE62254 database to distinguish between GCPM and non‐GCPM. The gastric cancer peritoneal metastases signature (GCPMs) was developed using DEGs. We analysed the effectiveness of GCPMs as indicators for prognosis, chemotherapy, and immune therapy response in GC patients. Subsequently, we analysed the correlation between GCPMs and immune microenvironment as well as immune escape in GC patients. Random forest model and immunohistochemistry was utilized to identify the crucial genes that can aid in the diagnosis of GCPM. We identified five DEGs and utilized their expression to construct GCPMs. Patients with high GCPMs had a higher likelihood of a poor prognosis, while those with low GCPMs appeared to potentially benefit more from chemotherapy. GCPMs were a dependable marker for predicting the response to immunotherapy. Additionally, GCPMs was found to be significantly linked to stromal score and cancer‐associated fibroblasts. SYNPO2 has been identified as the gene with the highest significance in the diagnosis of GCPM. Immunohistochemistry suggests that SYNPO2‐positive expression in tumour cells, fibroblasts, inflammatory cell may be associated with promoting peritoneal metastasis in GC. GCPMs have shown to be a promising biomarker for predicting the prognosis and response of GC patients to chemotherapy and immunotherapy. The use of GCPMs for individual tumour evaluation may pave the way for personalized treatment for GC patients in the future. [ABSTRACT FROM AUTHOR]

The peritoneum is a common site of metastases for gastrointestinal tumors that predicts a poor outcome. In addition to decreased survival, peritoneal metastases (PMs) can significantly impact quality of life from the resulting ascites and bowel obstructions. The peritoneum has been a target for regional therapies due to the unique properties of the blood–peritoneum barrier. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) have become accepted treatments for limited-volume peritoneal disease in appendiceal, ovarian, and colorectal malignancies, but there are limitations. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) improves drug distribution and tissue penetration, allowing for a minimally invasive application for patients who are not CRS/HIPEC candidates based on high disease burden. PIPAC is an emerging treatment that may convert the patient to resectable disease, and may increase survival without major morbidity, as indicated by many small studies. In this review, we discuss the rationale and benefits of PIPAC, as well as sentinel papers describing its application for gastric, colorectal, appendiceal, and pancreatobiliary PMs. While no PIPAC device has yet met FDA approval, we discuss next steps needed to incorporate PIPAC into neoadjuvant/adjuvant treatment paradigms, as well as palliative settings. Data on active clinical trials using PIPAC are provided. [ABSTRACT FROM AUTHOR]

Background: Obesity is a major global health problem and an important risk factor for colorectal cancer (CRC) is increased body weight. Obesity plays a role in the peritoneal dissemination of cancer; however, it is unclear whether this also applies for peritoneal dissemination of CRC. The purpose of this study was to provide insight in the role of obesity on the peritoneal dissemination of colorectal cancer. Methods: Of all patients diagnosed with CRC in the Netherlands in the first half of 2015, follow-up data was completed in 2019. Weight at time of primary diagnosis was categorized as underweight, normal weight, overweight, or obese. Logistic regression modelling was used to assess the association between weight and the presence of synchronous colorectal peritoneal metastases (CPM), and Cox regression modelling was used to assess the association between weight and metachronous CPM. Patient and tumor characteristics were taken into account. The analyses were adjusted for tumor stage, nodal stage, tumor location, and tumor histology. Results: In total, 6436 patients were included in this study. Two-hundred ninety-three (4.6%) patients presented with synchronous CPM at the time of primary diagnosis, while another 278 (5.1%) patients developed metachronous CPM after a median time of 16.5 months. Univariable and multivariable logistic regression modelling did not identify an effect of weight on the presence of synchronous CPM. Neither underweight (odds ratio [OR] 1.10, 95% CI 0.48–2.54), nor overweight (OR 0.96, 95% CI 0.71–1.29), or obesity (OR 0.84, 95% CI 0.56–1.26) was either positively or negatively associated with the presence of synchronous peritoneal metastases as compared to normal weight. Univariable and multivariable Cox regression modelling did not identify an effect of weight on the development of metachronous CPM. Neither underweight (HR 0.162, 95% CI 0.02–1.16), nor overweight (HR 1.07, 95% CI 0.82–1.39), or obesity (HR 1.02, 95% CI 0.73–1.16) was either positively or negatively associated with the presence of synchronous peritoneal metastases as compared to normal weight. Conclusion: CRC patients who are overweight or obese are not more at risk for the presence of synchronous CPM nor development of metachronous CPM than their normal-weight counterparts. [ABSTRACT FROM AUTHOR]