OBJECTIVE:Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has improved outcomes in colorectal cancer (CRC) patients with peritoneal metastases (PM), yet evidence regarding perioperative risk and long-term survival in those 75 years or older remains uncertain. The aim of this study was to evaluate whether age ≥75 years impacts on overall survival (OS) and postoperative in-hospital morbidity, according to Clavien-Dindo classification (CD), compared with patients aged <75 years. METHOD:This population-based study collected data from the National Swedish HIPEC Registry, including patients with colorectal PM operated with CRS-HIPEC. Patients were stratified by age (≤74 vs ≥75) with OS as primary outcome. Secondary outcomes were in-hospital mortality, postoperative morbidity and disease free survival (DFS). Potential variables assessed for association with OS were Complete Cytoreduction Score (CCS), Peritoneal Carcinomatosis Index (PCI) score, p/ypN stage of the primary tumor, postoperative morbidity and age. RESULTS:A total of 592 patients were operated between 2004 and 2021, of which 553 were ≤74 years and 39 were ≥75 years. OS did not differ between age groups (p = .951). Factors affecting OS negatively were high CCS (p = .004), PCI ≥21 (p = .009) and p/ypN2 (p = .041). No difference was observed in DFS (p = .525). The rate of CD grade III-IV was 27% in patients ≤74 years and 21% in patients ≥75 years (p = .495). The in-hospital mortality rate was 1.3% in patients ≤74 and none in patients ≥75 years. Reoperation rates were similar between groups. CONCLUSION:These results indicate that age above 74 should not automatically exclude patients from undergoing CRS-HIPEC. Careful selection ensures favorable survival without an increase in postoperative morbidity.

BACKGROUND:Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment for peritoneal metastases (PM) of various origins. The spleen is frequently involved in advanced disease, making splenectomy a common procedure in CRS. This study aimed to evaluate postoperative complications and prognosis associated with splenectomy during CRS + HIPEC. PATIENTS AND METHODS:Data from patients undergoing CRS + HIPEC from 2012 to 2022 were retrospectively collected from a prospectively maintained HIPEC registry. Postoperative complications according to Clavien-Dindo, overall survival (OS), and disease-free survival (DFS) were compared between patients undergoing splenectomy (n = 109) and the control group without splenectomy (n = 282). Cox proportional hazards models were used to identify independent prognostic factors. RESULTS:The splenectomy group had significantly higher PCI (median 25 vs. 8, p < 0.001) and more frequent diaphragmatic peritonectomy (83% vs. 70%, p < 0.001). High PCI was an independent predictor for splenectomy (adjusted OR 1.18, 95% CI 1.12-1.24). In univariable analysis, the likelihood of severe postoperative complications (Clavien-Dindo grade 3-4) was higher after splenectomy (OR 1.77, 95% CI 1.12-2.80), with increased rates of sepsis and kidney failure. In multivariable analysis, diaphragmatic resection (adjusted OR 4.81, 95% CI 1.99-11.61) was associated with severe complications, whereas splenectomy was not. Splenectomy was also not a predictor of OS and DFS after multivariable adjustment. In contrast, PCI ≥20 and synchronous liver resection were associated with worse OS. CONCLUSION:The need for splenectomy during CRS + HIPEC reflects more advanced peritoneal disease; however, splenectomy is not an independent risk factor for postoperative complications. Likewise, it does not independently affect overall or disease-free survival.

OBJECTIVE:To explore physical activity before and up to three months after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, understand patients' experiences of physical activity, recovery, and support needs, and integrate findings using a mixed methods approach. METHODS:A longitudinal convergent mixed methods design was employed, collecting data from 21 participants at a Swedish university hospital 2021-2023. Data collection included interviews and activity monitoring. Interviews were analyzed using reflexive thematic analysis and activity data were presented as time spent in moderate to vigorous physical activity. Based on the three-month follow-up, participants were categorized as having high or low activity according to World Health Organization recommendations. RESULTS:Participants in the high activity group described physical activity as meaningful and closely linked to mental well-being. The low activity group discussed physical activity in more general terms and put more emphasis on barriers to physical activity. High activity was not linked to lower perceived need for support, nor low activity to higher need. CONCLUSIONS:A discrepancy was identified between postoperative physical activity levels and perceived need for support. Physiotherapy-led support should be offered to all patients, regardless of activity level.

PURPOSE:Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRSH) or liver resection have led to increased survival in patients with peritoneal or liver metastases of colorectal cancer. Selected patients undergo concomitant CRSH and liver resection. Differences in survival and morbidity between patients who underwent concomitant surgery, CRSH or liver resection for peritoneal and/or liver metastases were compared. METHODS:Patients who underwent liver resection and/or CRSH for colorectal liver and/or peritoneal metastases, 2006-2016, were included. Regression analysis was used to evaluate the associations between baseline characteristics and survival. RESULTS:Overall, 634 patients were studied. Twenty-eight patients had peritoneal and liver metastases, 121 patients had peritoneal metastases only, and 485 patients had isolated liver metastases. Median survival after concomitant treatment was 23.8 months (95% CI 12.8-43.8), after CRSH 34.5 months (95% CI 27.1-41.9), and after liver resection 54.2 months (95% CI 47.4-61.0) (p < 0.001). Increased hepatic tumor burden (HR 3.2, 95% CI 1.8-5.8) and high-volume peritoneal disease (HR 6.0, 95% CI 3.7-9.8) were associated with decreased survival in multivariate analysis. Postoperative complications according to a Clavien-Dindo score > 3a were observed in 11% in the liver resection group, 15% in the CRSH group, and 11% in the concomitant treatment group (p = 0.945). CONCLUSIONS:Patients treated with concomitant surgery for liver and peritoneal metastases experienced a shorter median overall survival than patients treated for metastases at an isolated site but had a similar rate of severe postoperative complications. The extent of peritoneal spread seemed to impact survival more than the tumor burden in the liver.

Objectives:Surgical staging procedures are used to select patients with peritoneal metastases for surgery. We aimed to evaluate the impact of surgical staging procedures and the risk of abdominal wall recurrences in patients with peritoneal metastases scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Methods:Data were collected from a prospective maintained HIPEC register January 2012-December 2019. Patients with colorectal peritoneal metastases were included. Information about surgical staging procedures was registered. Results were then compared with those registered at definite CRS-HIPEC surgery and survival was analysed in relation to surgical staging procedures. Results:In total, 138 patients were included, of whom 32 had undergone a surgical staging procedure before CRS-HIPEC. Median overall survival in the surgical staging group was 1.89 years and in the non-staging group 3.07 years (p=0.060). In the surgical staging group, eight patients developed abdominal wall recurrences (25 %) compared with three (3 %) in the non-staged group. Eight staged patients (25 %) were considered inoperable at definite surgery (open-close). PCI score (p<0.001) was higher at definite surgery in patients who had undergone a staging laparoscopy. Factors associated with shorter overall survival in multivariate analysis were: open and close, PCI ≥21 and presence of signet ring cells. However, a staging procedure was not associated with a shorter overall survival. Conclusions:Surgical staging procedures is a valuable assessment of inoperability, though at the expense of more frequent abdominal wall recurrences. Imaging-based strategies may provide useful insights into whether surgical staging is the most effective approach for patient selection.

Objectives:The effects of preoperative chemotherapy have been poorly studied in colorectal cancer with peritoneal metastases (CRC-PM). This study evaluated preoperative chemotherapy from the first multi-disciplinary team meeting (MDT) decision, focusing on the response rates, surgical outcomes, and survival. Methods:This retrospective cohort study analyzed consecutive patients with resectable or potentially resectable CRC-PM evaluated at Uppsala University Hospital's peritoneal-MDT between March 2019 and December 2023. Kaplan-Meier curves and Cox-regression analyses were used for survival analysis. Results:Of 179 patients, 81 underwent upfront surgery; 52 received doublet chemotherapy and 46 received doublet with targeted therapy. Targeted group showed a 52 % overall response rate vs. 36 % for doublet group (p=0.14), with patients selected for CRS and HIPEC at a 52 % vs. 31 % rate, respectively, p=0.086. The median overall survival was superior in the targeted group than in the doublet group (intention-to-treat with all patients included): 21 (95 %CI: 18-35) vs. 17 (95 %CI: 14-22) months (p=0.027). The VEGF-targeted therapy outperformed EGFR-targeted therapy: 32 (95 %CI: 21-Not reached) vs. 15 (95 %CI: 11-40) months (p=0.042). Conclusions:Preoperative chemotherapy with targeted antibodies improves overall survival in CRC-PM in patients that are not candidates for upfront CRS and HIPEC. Bevacizumab is associated with improvement over EGFR targeted treatment in a subgroup analysis.

Pathogen invasion of intestinal epithelial cells (IECs) is a key gut infection event. The dynamics of this process in intact epithelia and the factors governing IEC susceptibility remain underexplored. We present a resource for live-cell infection imaging in human enteroid-/colonoid-derived IEC layers across maturation states and in the presence or absence of soluble mucus production. Utilization of this resource shows how human IEC maturation fortifies the apical surface against invasion by Salmonella Typhimurium (S.Tm). Immature IEC layers appear permissive to S.Tm invasion, but maturation toward an enterocyte/colonocyte phenotype reduces the susceptibility by up to 10-fold. This shift couples to downregulated expression of actin regulatory proteins exploited by the pathogen, an increased dependence on the S.Tm effector SipA, and the build-up of the apical IEC glycocalyx linked to surface-attached mucins like MUC13 and nullifiable by StcE-enzyme treatment. This underscores how the maturation state of human IECs governs susceptibility to bacterial invasion.

Despite their relatedness, Salmonella and Shigella enteropathogens differ in infectious dose, pathogenesis, and disease kinetics. The prototype strains Salmonella enterica serovar Typhimurium (Salmonella) and Shigella flexneri (Shigella) use Type-3-secretion-systems (T3SSs) to colonize intestinal epithelial cells (IECs). However, they have evolved unique sets of T3SS effectors and accessory virulence factors. A synthesis of how these differences impact the temporal progression of infection in non-transformed human epithelia is missing. Here, we followed Salmonella and Shigella infections of human enteroids and colonoids by time-lapse imaging to pinpoint virulence factor modules that shape the divergent epithelial colonization strategies. By an apical targeting module that integrates flagella and the SPI-4-encoded adhesin system with T3SS-1, Salmonella accomplishes appreciable numbers of apical IEC invasion events. These are promptly counteracted by IEC death, thus fostering a polyclonal iterative epithelial colonization strategy. The lack of a corresponding apical targeting module in Shigella makes this pathogen reliant on external factors, for example, preexisting damage, for rare apical access to the intraepithelial environment. However, Shigella compensates for this ineptness by an intraepithelial expansion module reliant on the tight coupling of OspC3-dependent temporal delay of cell death and IcsA-mediated mobility. This module enables intraepithelial Shigella to evade the IEC death response just long enough to expand laterally, thus fostering an essentially monoclonal colonization strategy. Taken together, the study reveals how a small set of virulence factors shapes divergent epithelial colonization strategies by related enterobacteria.IMPORTANCEPathogenic bacteria employ partially overlapping sets of virulence factor functions to colonize host epithelia but can differ markedly in their pathogenesis and disease kinetics. This work combines bacterial genetics and real-time microscopy in enteroids and colonoids to decipher the divergent colonization strategies of Salmonella enterica Typhimurium and Shigella flexneri-two major enteropathogens-in non-transformed human intestinal epithelia. The results reveal how virulence factor modules enabling efficiency at either the invasion step (Salmonella) or the intraepithelial expansion stage (Shigella) drive the radically different infection cycles of these related enterobacteria. Moreover, our work emphasizes how real-time studies in infection models that retain primary host cell features are critical to understanding infectious disease progression.

BACKGROUND:Prediction of open-close and long-term outcome is challenging in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic scores often include factors not known at baseline. Therefore, we aimed to analyze whether patterns of preoperative tumor markers could aid in prediction of open-close surgery and outcome in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM). PATIENTS AND METHODS:All patients accepted for CRS and HIPEC for PMP or colorectal PM at Uppsala University Hospital in 2013-2021 were included. The tumor markers CEA, CA19-9, CA125, CA72-4, and CA15-3 were clustered using the k-means algorithm; the average silhouette width determined the optimal numbers of clusters. RESULTS:Clustering of patients with PMP (n = 138) and colorectal PM (n = 213) resulted in two clusters each. PMPCluster-1 (n = 124) had a 5-year overall survival (OS) of 77% (95% CI 69-85%), 11 (9%) open-close surgeries, and a median peritoneal cancer index (PCI) of 17. PMPCluster-2 (n = 14) patients had poorer prognosis (36%, 95% CI 15-85%, p = 0.003), more often open-close (n = 6, 43%, p = 0.002), and higher PCI (median 36, p < 0.001). ColorectalCluster-1 (n = 191) had a 5-year OS of 28% (95% CI 21-37%), median PCI of 11, and 38 (20%) open-close surgeries. ColorectalCluster-2 (n = 22) had poorer prognosis (10%, 95% CI 3-36%, p = 0.02), higher PCI (median 26, p < 0.001), higher completeness of cytoreduction score (p = 0.005), but no difference in open-close surgery (n = 6, 27%, p = 0.411). PMPCluster-2 and ColorectalCluster-2 were characterized by markedly elevated tumor markers. Open-close surgery was unusual in cases of normal CA72-4. CONCLUSIONS:Elevation of several preoperative tumor markers is associated with poor prognosis and increased risk of open-close. CA72-4 deserves increased attention.

Background Surgical staging procedures are used to select patients with peritoneal metastases for surgery. We aimed to evaluate the prognostic impact of surgical staging procedures and the proportion of abdominal wall metastases in patients with peritoneal metastases scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Methods Data were collected from a prospective maintained HIPEC register 2012 to December 2019. Patients with peritoneal metastases originating from colorectal or appendiceal adenocarcinomas were included. Information about surgical staging procedures was registered. Results were then compared with those registered at definite CRS-HIPEC surgery and survival was analysed in relation to surgical staging procedures. Results In total, 167 patients were included, of whom 45 had undergone a surgical staging procedure before CRS-HIPEC. Median overall survival in the surgical staging group was 1.89 years and in the non-staging group 3.19 years (p = 0.01). In the surgical staging group, eleven patients developed abdominal wall metastases (24%) compared with four (3%) in the non-staged group (p < 0.001). Fifteen staged patients (33%) were considered inoperable at definite surgery (open-close). PCI score (p < 0.001) was higher at definite surgery in patients who had undergone a staging procedure. Factors associated with shorter overall survival in univariate analysis were: a separate surgical staging procedure prior to CRS-HIPEC, PCI ≥ 21 and presence of signet ring cells. However, a staging procedure was not associated with a shorter overall survival in multivariate analysis. Conclusion Surgical staging procedures are associated with a risk of inoperability and development of abdominal wall metastases. The use of a separate surgical procedure for staging patients before CRS-HIPEC should be selective.

BACKGROUND:The treatment for patients with colorectal cancer with metastases to the peritoneum is complex and may involve both surgery and chemotherapy. Circulating tumor cells (CTCs) have been poorly investigated in peritoneal metastatic colorectal cancer. The aim of the study is to examine the role of CTCs as a biomarker for monitoring disease progression, treatment response, and residual disease using CellMate - a new promising in vitro diagnostic platform technology. MATERIALS AND METHODS:The authors prospectively followed the clinical outcomes of 46 patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer with peritoneal metastases and examined whether CTCs were present the week of surgery. The CTC measurements were made with the CellMate technology, which is a platform technology to detect CTCs based on the difference in biomechanical properties compared to blood resident cells. The study was registered online (ClinicalTrials.gov). RESULTS:CTCs were detected in 17 (37%) patients. The presence of CTCs was associated with shorter recurrence-free survival and overall survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Both recurrence-free survival (HR 4.00, 95% CI: 1.15-13.9; P =0.029) and overall survival (HR 5.91; 95% CI: 1.18-29.7; P =0.03) were significantly worse if CTCs were detected after neoadjuvant treatment. In the subgroup of patients with CTCs detected, adjuvant therapy tended to improve the prognosis while in CTC negative patients it did not. CONCLUSIONS:Pending a prospective multicenter trial to validate these findings, CTCs may in the future be used as a dynamic personalized biomarker for prognostication, predicting response to therapy, and for monitoring disease progression in colorectal cancer with metastases to the peritoneum.

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.

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.

The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.

BACKGROUND:Laparoscopic lavage (LPL) has been suggested for treatment of non-feculent perforated diverticulitis. In this observational study, the surgical treatment of diverticular disease in Sweden outside prospective trials was investigated. METHODS:This population-based study used the National Patient Register to identify all patients in Sweden with emergency admissions for diverticular disease, as defined by ICD codes from July 2014 to December 2020. Demographics, surgical procedures and outcomes were assessed. In addition, register data since 1997 were retrieved to assess co-morbidities, previous abdominal surgeries, and previous admissions for diverticular disease. RESULTS:Among 47 294 patients with emergency hospital admission, 2035 underwent LPL (427 patients) or sigmoid resection (SR, 1608 patients) for diverticular disease. The mean follow-up was 30.8 months. Patients selected for LPL were younger, healthier and with less previous abdominal surgery for diverticular disease than those in the SR group (P < 0.01). LPL was associated with shorter postoperative hospital stay (mean 9.4 versus 14.9 days, P < 0.001) and lower 30-day mortality (3.5% versus 8.7%, P < 0.001). Diverticular disease-associated subsequent surgery was more common in the SR group than the LPL group except during the first year (P < 0.001). LPL had a lower mortality rate during the study period (stratified HR 0.70, 95% c.i. 0.53-0.92, P = 0.023). CONCLUSION:Laparoscopic lavage constitutes a safe alternative to sigmoid resection for selected patients judged clinically to require surgery.

Abstract Introduction Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has entailed better prognosis and overall survival for patients with peritoneal metastasis (PM) from colorectal cancer (CRC). However, data on perioperative complications and long-term survival of this procedure in elderly patients (≥75 years) are scarce. The aim of this study was to determine if age ≥75 impacts overall survival (OS) and postoperative morbidity. Method This population-based study collected data from the National Swedish HIPEC Registry, including patients with PM from CRC operated with CRS-HIPEC. We stratified patients by age (≤74 vs ≥75) with overall survival as primary outcome. Secondary outcomes included PCI-score, N-stage, postoperative morbidity, early mortality and time to relapse. Result A total of 592 patients were identified of which 553 were ≤74 year whereas 39 were ≥75. There was no difference in OS (p=0.951, Fig. 1). Factors affecting OS negatively were CC-1 (p=0.004), PCI ≥20 (p=0.009), nodal status N2 (p=0.041), but not age ≥75. No difference was noted for time to relapse (p=0.525) and in case of recurrent disease, curative intention was offered more frequently to patients ≤69 years (p=0.045). Serious postoperative complication (Clavien-Dindo grade III-IV) rate was 27% in patients ≤74 year and 21% in patients ≥75. The in-hospital mortality rate was 1.3% in patients ≤74 year and zero in patients ≥75year. No difference was observed in in-hospital morbidity (p=0.540) or reoperations (p=0.749). Discussion These results support that advanced age is not a contraindication to perform CRS-HIPEC in selected patients with PM from CRC.

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.

Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15-30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.

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.

Appendiceal tumors are uncommon and, at times, discovered incidentally during histological examination. The histopathological classification of the disease is complex and has generated some controversy. The analysis of circulating tumor cells can be used for the early detection of metastatic potential. The aim of the present study was to examine the prognostic value of circulating tumor cells in patients with appendiceal tumors and peritoneal metastases. To our knowledge, this is the first study to examine CTCs in appendiceal tumors. We performed a prospective cohort study of consecutive patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy between 2015 and 2019 at a HIPEC referral center. In total, 31 patients were included in the analysis, and circulating tumor cells were detected in 15 patients (48%). CTC positivity was not associated with overall or recurrence-free survival, nor was it correlated with PCI score or histopathological grading. Surprisingly, however, CTCs were found in almost half the patients. The presence or quantities of these cells did not, on their own, predict systemic metastatic potential during the observed time, and they did not appear to significantly correlate with the oncological outcomes recorded.