Logo: to the web site of Uppsala University

Background

Research into the gut microbiome and its possible association with anastomotic leakage after colorectal surgery has increased recently with the growing availability of sequencing techniques. There is a lack of systematic reviews addressing specifically microbiomic differences between patients with anastomotic leakage and patients with a successful anastomotic healing. The objective was to systematically review the current research on the microbiome and its effect on the risk of anastomotic leakage in colorectal cancer.

Methods

Pubmed/Medline, Cochrane, and Google scholar were searched on 14th February 2025, to identify relevant publications with the following inclusion criteria: colorectal surgery, microbiome sequencing data, anastomotic leakage as endpoint, and comparative groups. Exclusion criteria were studies conducted exclusively on animals, non-peer-reviewed studies, review articles, and unavailable full text. Alpha/beta diversity and microbiomic functional analyses were the focus of the results.

Results

From 112 studies, 11 studies including 551 patients were included: 143 patients with anastomotic leakage and 408 as controls. Alpha diversity differences were found in 7 of 11 studies—1 of 4 with preoperative sampling versus 6 of 7 studies with intra/postoperative sampling (P = 0.044). Beta diversity differences were found in 5 of 11 studies. Three studies reported on functional analyses, with one study demonstrating an association between methanogenesis and anastomotic leakage. Bacterial abundance was inconsistent across the studies. Three studies involving rodent models indicated a causal effect of the clinical microbiome.

Conclusion

Evidence implicates the gut microbiome as a factor associated with anastomotic leakage in colorectal cancer surgery, with three studies suggesting a causal relationship. There is a shortage of studies evaluating cross-species functional profiling. Optimal sampling should be performed during surgery.

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: 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: Colorectal cancer with peritoneal metastases (PM) presents a significant therapeutic challenge. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is one option to prolong survival. While completeness of cytoreduction (CC) score 0 is associated with improved outcomes, the clinical value of near-complete CC-score 1 versus open-close laparotomy (CC-3) remains unclear.

Methods: This retrospective study evaluates overall survival (OS) in patients with colorectal cancer PM scheduled for CRS and HIPEC from 23 global peritoneal-surface oncology centers from 2006 to 2023. A propensity score matching was performed using tumor location (colon/rectum), lymph node status, liver metastases, signet-ring histology, preoperative chemotherapy, peritoneal cancer index, and treatment year. Matching was performed using the nearest neighbor method with a caliper of 0.1, chosen after several iterations to optimize intergroup balance. Balance was assessed using standardized mean differences. Sensitivity analyses with alternative calipers and multivariable Cox regression in the unmatched cohort were considered to test the robustness of the findings. The study time-period was divided into 4 equal quartiles for analysis.

Results: In the unmatched cohort (n = 284), patients with CC-1 had significantly longer median OS compared to those with CC-3 (22.2 vs. 9.4 months, p < 0.001). After 1:1 matching (n = 172), the OS advantage of CC-1 persisted, with a median OS of 18.9 months (95 % CI: 14.2-24.7) versus 10.5 months (95 % CI: 9.4-12.3) for CC-3, p < 0.0001, HR 0.4 (95 % CI:0.27-0.56). Multivariable Cox regression confirmed CC-1 as a significant predictor of survival (HR: 0.15, 95 % CI: 0.08-0.26). The CC-1 proportion went from 55 to 65 % in time-periods 1 & 2-39 % in period 3, to 11 % in period 4; leading to significantly reduced survival rates in the latter time-periods 3 & 4.

Discussion: Near complete cytoreduction is associated with improved overall survival compared to open-close laparotomy. Prospective or standardized multicenter analyses will be required to confirm the clinical value of a near complete cytoreduction.

Aim

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard treatment for peritoneal metastases (PM) of colorectal or appendiceal origin. Rectal anastomotic leakage (RAL) or rectal stump blow-out is a serious complication following rectal resection after CRS-HIPEC. This study aimed to compare outcomes between ileo-/colorectal anastomosis and rectal stump procedure and to identify risk factors for RAL and blow-out.

Method

Data were retrospectively collected between 2012 and 2024 from a prospectively maintained HIPEC Registry and supplemented with the review of medical records. Postoperative complications and the prevalence of RAL or blow-out were registered. Pearson's chi-squared test was used to compare differences in categorical variables. Logistic regression was used to identify risk factors for RAL and blow-out.

Results

Among 1271 CRS-HIPEC procedures, 332 involved rectal resections. Patients received either an ileo-/colorectal anastomosis (n = 158) or had a rectal stump procedure (n = 174). RAL occurred in 5.7% and blow-out in 2.9% (p = 0.201). In the rectal stump group, patients were older (65 vs. 59 years; p = <0.001), had higher PCI scores (p = 0.031) and more often had received neoadjuvant treatment (p = 0.025). Logistic regression showed no independent association between RAL and type of rectal reconstruction (OR 1.99; 95% CI: 0.61–6.51), low anastomotic level (OR 2.17; 95% CI: 0.50–9.42) or peritoneal cancer index >21 (OR 6.47; 95% CI: 0.84–50.1).

Conclusion

Both reconstruction strategies following rectal resection in CRS-HIPEC were associated with low rates of RAL or blow-out. No independent risk factors were identified, indicating that the choice of surgical approach should be individualized based on clinical context rather than presumed leakage risk.

Introduction: Appendiceal adenocarcinoma represents a diagnostic and therapeutic challenge since it is prone to early lymphatic and peritoneal spread. We aimed to analyze the proportion of lymph node metastases in completion right hemicolectomy specimens, risk factors for peritoneal metastases (PM), and prognosis after definitive treatment.

Methods: Ninety-three patients with appendiceal adenocarcinoma scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in Uppsala 2004-2020 were identified from a prospectively maintained registry. Risk factors for PM were assessed based on the presence (CT + group, n = 55) or absence (CT - group, n = 37) of visible PM at baseline CT scan. Prognostic factors were analyzed based on the actual presence (PM group, n = 66) or absence (no PM group, n = 27) of PM.

Results: The median age was 60 (26-78). Forty-eight patients were women. Resection of PM at initial surgery indicated an 80 % risk of finding PM at a follow-up exploration. R1 appendectomy and perforated appendix had a similar risk for PM (24 %,26 %) which increased to 38 % if both were present. Regional lymph node metastases occurred in 31 % in the CT + group vs. 14 % in the CT- group (p = 0.005) and was associated with poor survival HR 5.16 (1.49-17.81). The 5-year OS and DFS rates were 54 % and 29 % in the PM group.

Conclusions: Patients with certain risk factors have a high likelihood of PM despite a normal CT scan, which justifies selective exploration at a HIPEC center. Regional lymph node spread supports the current practice of completion right hemicolectomy and is a significant prognostic factor.

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.