Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown survival benefits in select patients with peritoneal metastases (PM) from colorectal cancer (CRC). Molecular alterations, particularly RAS/BRAF mutations and Microsatellite Instability (MSI), play crucial roles in prognostic stratification and treatment planning, influencing both disease-free survival (DFS) and overall survival (OS). This scoping review evaluates the prognostic role of MSI and RAS/BRAF mutations in patients with PM-CRC treated with CRS-HIPEC.

A literature search was conducted across several databases to identify papers published between 2000 and September 2024. We selected 18 publications that considered DFS and OS as primary or secondary outcomes in patients with RAS/BRAF mutations and MSI following CRS-HIPEC treatment. Studies involving appendiceal cancer, peritoneal disease from non-CRC, pediatric patients, or subjects not treated with CRS-HIPEC were excluded.

Most studies suggest that RAS and BRAF mutations have a negative influence on survival outcomes. While inconsistencies exist, RAS mutations are generally associated with worse DFS. Specific KRAS subtypes such as KRASMUT2 or KRAS G12V and the BRAF V600 variant correlate with poorer prognosis. MSI status appears to attenuate the adverse effects of RAS/BRAF mutations on survival, although conflicting data persist.

RAS and BRAF mutations correlate with poorer outcomes in PM-CRC, underscoring the need for mutation-informed strategies to refine HIPEC and systemic therapies. Recognizing subtypes may improve patient selection for CRS-HIPEC, optimizing both local disease control and long-term survival. Future research should incorporate these molecular profiles to enhance therapeutic decision-making and better address this challenging condition.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) can improve survival in colorectal cancer (CRC) patients with peritoneal carcinomatosis (PC). The presence of synchronous liver metastases (LMs) often precludes patients from CRS/HIPEC; however, multiple studies suggest that CRS/HIPEC with liver-directed treatments may be beneficial. This systematic review examines outcomes and selection factors in CRC patients with PC and LM treated with CRS/HIPEC and liver-directed therapy.

A systematic review and meta-analysis was performed using the PubMed, EMBASE, and Web of Science databases from 2009 to 2024. The outcomes included patient selection factors, overall survival (OS) and disease-free survival (DFS).

A total of 482 articles were retrieved, of which 17 retrospective studies met the inclusion criteria, comprising a total of 988 patients. Liver-directed therapy with CRS/HIPEC for PC and LM was associated with 3- and 5-year OS rates of 47% and 37%, respectively, with a median survival range of 15.3-47.6 months. The adjusted 1- and 3-year DFS rates were 34% and 23%, respectively, with a median DFS range of 6.2-29.4 months. Patients with PC and LM were more likely to have received preoperative systemic therapy (86%), undergone minor liver resection (90%), had a limited burden of LM (mean of three lesions, median size of 1.4-3 cm), and limited PC (mean peritoneal cancer index of 13).

This study indicates that CRS/HIPEC with liver-directed therapy can yield favorable survival outcomes for well-selected CRC patients with limited PC and LM. Further trials are needed to confirm its efficacy and refine optimal patient selection.

The survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) has been well defined at the time of interval cytoreductive surgery, but the role of HIPEC remains uncertain for patients with newly diagnosed advanced ovarian cancer in the upfront setting. The present study aimed to report the updated long-term survival outcomes after 5 years of follow-up from our previous multicenter retrospective cohort study to compare primary cytoreductive surgery (PCS) plus HIPEC with PCS alone among women with stage III epithelial ovarian cancer.

This study was conducted at five high-volume gynecological medical centers in China from January 2010 to May 2017. Eligible patients with complete data were treated with either PCS combined with HIPEC or PCS alone. The 5-year overall survival (OS) rate was updated to compare PCS plus HIPEC with PCS alone. The inverse probability of treatment weighting (IPTW) method based on a propensity score model for each patient was used to control the confounding factors and evaluate the effect of HIPEC.

Data from 789 patients, a total of 584 eligible stage III epithelial ovarian cancer patients were ultimately included in the analysis (PCS-plus-HIPEC group, n = 425; PCS-alone group, n = 159). After IPTW adjustment, the median OS was 44.5 (95% CI, 40.1-49.1) months in the PCS-plus-HIPEC group and 32.4 (95% CI, 28.8-40.3) months in the PCS-alone group (weighted hazard ratio, 0.74; 95% CI, 0.59-0.93; p = 0.006). At 5 years, the OS rates were 37.9% (95% CI, 33.0%-42.8%) in the PCS-plus-HIPEC group and 26.4% (95% CI, 18.9%-34.6%) in the PCS-alone group (p = 0.007). After stratification into optimal and suboptimal cytoreduction subgroups, patients in the PCS-plus-HIPEC group maintained a greater association with improved OS than those in the PCS-alone group. Among the women who underwent optimal cytoreduction in the PCS-plus-HIPEC group and PCS-alone group, the median OS was 49.9 (95% CI, 45.2-58.4) months and 37.8 (95% CI, 30.5-53.0) months (p = 0.042) while the 5-year OS rate was 43.7% (95% CI, 37.7%-49.6%) and 33.2% (95% CI, 23.3%-43.5%), respectively (p = 0.040). Meanwhile, for those treated with suboptimal cytoreduction subgroup in the PCS-plus-HIPEC and PCS-alone groups, the median OS was 28.4 (95% CI, 22.2-39.9) months and 20.6 (95% CI, 10.6-32.4) months (p = 0.099) while the 5-year OS rate was 22.4% (95% CI, 15.1%-30.5%) and 12.2% (95% CI, 4.4%-24.2%), respectively (p = 0.060). The median follow-up period was 87.2 (95% CI, 85.1-92.7) months.

The updated results indicate that the addition of HIPEC is associated with improved long-term survival outcomes beyond 5 years for patients with stage III epithelial ovarian cancer in the upfront setting.

Cytoreductive surgery has shown survival benefits for colorectal cancer (CRC) patients with peritoneal metastasis. However, the optimal extent of peritonectomy remains controversial in cases of limited peritoneal metastases. This study modified selective pelvic peritonectomy (SPP) into subtotal pelvic peritonectomy (STPP) for metastasis confined to pelvic cavity, and aimed to evaluate its feasibility, safety, and impact on survival outcomes.

CRC patients with limited peritoneal metastasis confined to the pelvic cavity who underwent CC0 (no macroscopic residual cancer remained) resection were included from a prospectively collected database. Surgical complications, disease-free survival (DFS), and overall survival (OS) were analyzed.

A total of 67 patients were included (26 in the STPP group and 41 in the SPP group). Clinically, STPP was found to be feasible and without increased surgical complications or mortality rates. At a median follow-up of 33.9 months, the 3-year DFS was 65.9 % and 30.7 % in STPP and SPP groups, respectively (P= 0.002). The 3-year OS was 84.1 % and 68.5 % in STPP and SPP groups, respectively (P= 0.006). Moreover, STTP was independently associated with improved DFS (HR = 0.351, 95 % CI 0.165-0.745, P= 0.006) and OS (HR = 0.324, 95 % CI 0.116-0.902, P=0.032). Female gender was also independently associated with poor DFS (HR = 2.146, 95 % CI 1.078-4.271, P= 0.031). Among 24 female patients with remaining ovaries, 9 (37.5 %) cases developed metachronous ovarian metastasis, and of these 6 underwent a second operation.

Subtotal pelvic peritonectomy is associated with promising long-term outcomes in CRC patients with peritoneal metastasis confined to the pelvic cavity. Prophylactic bilateral oophorectomy should be strongly considered during cytoreductive surgery.

Colorectal peritoneal metastases (CPM) are the third most common site of metastatic spread of colorectal cancer and are associated with worse survival than other sites of metastatic disease. In recent years tumoral circulating tumoral DNA (ctDNA) mutational status has been increasingly utilized in clinical decision making for metastatic colorectal cancer patients despite its utility in CPM being poorly understood. Here we describe standard of care performed mutational profiles and associated outcomes for unresectable CPM patients, with a contextual comparison to 160 unresected colorectal liver metastases (CLM) patients. Of 508 patients, 288 (57 %) had CPM alone and 220 (43 %) had CPM with extraperitoneal metastases. Patients with synchronous CPM and CLM had worse overall survival (HR 1.67 [95 %CI 1.26-2.22]). Mutations in ctDNA were noted in 110/145 (75.9 %) of CPM patients, with mutations in KRAS or PIK3CA ctDNA being associated with worse survival. Importantly, the association between tumoral mutational profile and survival differed by site of metastatic disease. The prognostic significance of specific mutations, particularly BRAF and KRAS, differs between patients with CPM and CLM, and supports the distinct biology of these metastatic sites and the importance of tissue and circulating genomic profiling to risk-stratify these patients according to site of metastasis.

Over 50% of patients with colorectal cancer develop metastatic disease. Although systemic therapy remains the backbone of palliative treatment, select patients may be candidates for surgical resection with curative intent. Given increasing evidence of the association between metastasectomy and prolonged survival, surgery has acquired an increasingly central role in the management of liver, lung, and peritoneal metastases. This is compounded by accumulating advances in local and systemic treatments that have allowed for expansion of the resectability pool, bringing the potential for curative surgical treatment to increasing numbers of patients with stage IV disease. However, as the boundaries of resectability are pushed, patient selection and consideration of tumor-related and technical factors are imperative to the identification of patients for whom surgery would be of the greatest benefit.

Diffusion-weighted MRI (DW-MRI) is a promising tool for selecting patients with colorectal peritoneal metastases for cytoreductive surgery (CRS). This study investigated whether surgeons can predict the extent of CRS based on preoperative MRI findings.

This single-centre retrospective study included patients who underwent CRS-HIPEC after preoperative MRI. An expert abdominal radiologist showed MR images to three experienced surgeons, who independently predicted the probability of achieving a complete resection by scoring which of 29 anatomical structures would be resected during CRS-HIPEC. Other predictions were surgery duration, number of anastomoses and CRS-HIPEC resulting in a stoma. Predictions were confirmed using surgical reports and histopathology.

Data from 29 patients were analyzed. The median surgical PCI was 6 [range 0-19]. Complete resection was achieved in all patients with a total of 216 structures resected. All three surgeons had a negative predicting value (NPV) above 75% for most anatomical structures, and a positive predicting value (PPV) ranging from moderate (50%-75%) to good (>75%). The PPV for CRS-HIPEC resulting in a stoma ranged between 71% and 100%, and for colon anastomoses between 57% and 77%. The ICC indicated good to excellent (≥0.75) agreement among surgeons' predictions for most structures.

Based on DW-MRI, the abdominal radiologist and surgeon are good at predicting the extent of the cytoreductive surgical procedure. Surgeons can use MRI findings for surgical planning and patient expectation management. However, adhesions and fibrosis interpreted as possible tumors during surgery and not clearly depicted small metastases on MRI can lead to more resections than anticipated.

This study explored the lived experience of patients with colorectal peritoneal metastases undergoing cytoreductive surgery and their carers, including the decision to undergo radical surgery, recovery, and long-term survivorship.

This qualitative study was conducted in a tertiary cytoreductive surgery center. Semi-structured interviews were conducted with an experienced researcher to explore participants' experiences, challenges, and reflections during different treatment stages. In-depth thematic analysis was performed on interview transcripts using a phenomenological approach to identify key major and minor themes.

Thirteen interviews were conducted, with 5 major themes and 11 minor themes identified. Understanding diagnosis and treatment implications-survival was a key driver in decision making, although many did not feel they had a choice or understood the magnitude of the intervention. Adjustment to uncertainly-uncertainties regarding surgical intervention, its impacts and long-term recurrence, led to significant burden. Unmet supportive care needs-psychology services and patient-led support groups have key roles in addressing long-term support needs. A positive impact from multidisciplinary care teams-allied health involvement pre- and postoperatively was associated with a positive experience. Unexpected long-term physical effects-unexpected physical effects impacted quality of life during long-term survivorship.

Patients and carers undergoing cytoreductive surgery for colorectal peritoneal metastases endure a difficult journey and decision-making process; an understanding of their lived experience can improve the informed consent process and target supportive care endeavors to areas of need.

Peritoneal carcinomatosis (PC) represents a challenge in the management of metastatic colorectal cancer (mCRC) because of the difficulties in diagnosis, tumor burden assessment, and in selecting the optimal treatments. A critical limitation is the lack of robust prognostic and predictive biomarkers, largely relying on serum markers (e.g., carcinoembryonic antigen) or the peritoneal carcinomatosis index (PCI) for disease extent. Circulating tumor DNA (ctDNA)-genomic fragments shed by tumor cells into the bloodstream-is now recommended by international guidelines for mCRC management. Its potential extends to PC, where it may enhance diagnostic, therapeutic, and follow-up strategies. However, PC from CRC (PC-CRC) is associated with lower ctDNA levels and detection rates compared to other metastatic sites, posing a challenge for its clinical utility. To address these limitations, peritoneal fluid analysis has emerged as a promising alternative, with peritoneal tumor DNA (ptDNA) detected at higher concentrations in this anatomical space. Integrating ctDNA and ptDNA may offer a deeper understanding of PC-CRC biology and provide more precise tools for managing this complex disease. This approach has the potential to revolutionize the treatment paradigm for PC-CRC, bringing precision medicine even to this subgroup of patients traditionally associated with poor outcomes. This review aims to evaluate the diagnostic, prognostic, and therapeutic implications of ctDNA and ptDNA in PC-CRC, highlighting current limitations and future directions.

This study aimed to analyze the morbidity, mortality, and survival outcomes in patients with peritoneal surface malignancies who were initially considered candidates for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) but were found to have unresectable disease, resulting in nontherapeutic exploratory laparotomy.

We evaluated data from our referral center for the treatment of peritoneal surface malignancies between January 2008 and December 2022. Adverse events following nontherapeutic laparotomy were classified using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.

Among a cohort of 486 patients with peritoneal surface malignancies initially considered candidates for CRS + HIPEC, 46 cases (9.4%) were aborted due to the disease being deemed unresectable during exploratory laparotomy. The primary reasons for unresectability included extensive disease spread, observed in 28 patients, with massive small intestine involvement detected in 13 of these cases. The median duration of surgery was 90 min (range: 60-180 min). Postoperative complications occurred in 10 patients (22%), with a mortality rate of 4.3% (2 patients). Survival was significantly lower in patients who did not receive adjuvant systemic chemotherapy with palliative intent (4 months vs. 15 months, p < 0.01).

Exploratory laparotomy in patients with peritoneal surface malignancies considered for CRS with HIPEC carries a substantial risk of complications. Improved preoperative staging using advanced technologies such as radiomics and laparoscopy is expected to reduce the number of patients undergoing nontherapeutic laparotomy.

Ampullary adenocarcinomas are a rare disease. They can be classified anatomically or according to their histology into intestinal, pancreatobiliary, and mixed subtypes, with different subtypes having distinct prognoses and potential treatments. We report a clinical case of a patient with mixed type adenocarcinoma of the ampulla of Vater, with predominantly intestinal histology, associated with an isolated and synchronous peritoneal carcinomatosis. It is the only case reported in the literature of duodenal ampulla cancer with synchronous peritoneal metastases, with long-term survival.

A 53-year-old male patient with non-insulin-dependent diabetes presented with acute abdominal pain in the right hypochondrium. Images revealed dilatation of the biliary tract and the duct of Wirsung, without a clear obstructive factor. Upper gastrointestinal endoscopy revealed a tumor in the duodenal papilla. Biopsies confirmed an adenocarcinoma. In the first surgical step, a biliodigestive bypass was performed in association with resection of the carcinomatosis. Peritoneal metastases was found during the intraoperative period. Subsequently, chemotherapy with the folinic acid, fluorouracil, and oxaliplatin regimen was administered based on histology, and a favorable response was achieved. After a multidisciplinary discussion, the Whipple procedure was performed. A delayed biopsy showed disease-free margins. The patient achieved 5 years of overall survival in August 2024, and 4 years of disease-free survival in September 2024.

We conclude that an important value of this work is showing individualized treatment for a patient with cancer.

Following the PRODIGE-7 trial, surgeons have shifted to the use of Mitomycin-based HIPEC from Oxaliplatin for colorectal peritoneal metastasis. While preclinical studies have demonstrated the superiority of Mitomycin over oxaliplatin, clinical studies report variable results. The objective of the meta-analysis was to determine the most efficacious drug after cytoreduction for colorectal peritoneal metastasis.

he databases searched were PubMed, Cochrane Library, Scopus, CINHAL (EBSCO), and Google Scholar based on the following concepts: colorectal, peritoneal, cytoreduction, Mitomycin, and Oxaliplatin. The risk of bias was assessed using the Newcastle-Ottawa scale and certainty of the evidence was assessed using the GRADE Pro tool. The analysis was carried out using the log hazard ratio as the outcome measure for survival data. All syntheses used the Random-effects model and were reported for Oxaliplatin-based HIPEC with MMC as the reference.

Thirteen studies with 3406 patients were included in the quantitative meta-analysis. The pooled hazard ratio for overall survival was 1.03 (95 % CI: 0.786-1.349) from ten studies. Six studies reported disease-free survival and the pooled hazard ratio was 0.941 (95 % CI: 0.683-1.297). Both survival estimates had moderate statistical heterogeneity. The evidence was of very low certainty for all the outcomes due to the non-randomized nature of studies, clinical and statistical heterogeneity, serious risk of bias due to uncontrolled measured confounding, selection bias, and unequal follow-up durations.

Our systematic review and meta-analysis found no significant difference in survival outcomes or postoperative morbidity between MMC and Oxaliplatin-based HIPEC.

The study by Wu et al analyzed the correlation between nutritional and inflammatory markers and prognosis in patients with colorectal cancer peritoneal metastasis. The authors propose the neutrophil-to-lymphocyte ratio (NLR) as a predictor of overall survival (OS) and developed a nomogram incorporating NLR, hemoglobin (Hb), and peritoneal cancer index (PCI) to estimate 1- and 2-year survival. Although the nomogram shows high accuracy, the group of patients analyzed is heterogeneous with respect to the surgical treatment received, and no clear definitions are given for normal Hb and there is no reason for choosing a very high PCI (≥ 20). Patient selection for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy requires a multidisciplinary approach. Over-simplification of the selection pathway may deny access to curative treatments to patients who could benefit. While methodologically sound, the study does not consider the effect of treatment received on OS, thus introducing a potential bias.

Peritoneal carcinomatosis (PC), characterized by the dissemination of metastatic tumor cells throughout the peritoneal cavity from several gastrointestinal and gynecological malignancies, has significantly compromised patient survival. The standard of care is cytoreductive surgery with or without intraperitoneal chemotherapy. However, surgical resection often leaves behind microscopic or clinically occult disease due to the complex anatomy of the peritoneum, where intraperitoneal chemotherapy and systemic chemotherapy have shown limited success. To improve the therapeutic outcome, targeted therapy using radionuclides such as alpha, beta, and Auger emitters delivered by antibodies is actively being investigated. While preclinical murine models of PC have shown the potential of radioimmunotherapy (RIT) using various radioisotopes across a wide spectrum of antigen targets and tumor diagnoses with acceptable toxicities, successful clinical trials are lacking. Here, we retrospectively summarize preclinical and clinical PC studies, consider their translational potential, and examine paths to development that maximize the clinical benefit of RIT in this context.

Peritoneal membrane injury induces the activation of local fibroblasts and tissue remodelling, which ultimately can progress to fibrosis. Metastasis of colorectal cancer (CRC) to the abdominal cavity results in such peritoneal damage. Patients with colorectal cancer peritoneal metastasis (CPM) have a particularly poor prognosis, and CPM tumours are characterised by a high infiltration of fibroblasts. Here, we characterised the molecular and functional features of these fibroblasts, and investigated their interaction with other cells in the peritoneal microenvironment. Primary fibroblasts were isolated from 89 patients with different malignant and benign disorders of the peritoneum. We performed comprehensive analyses of single-cell and transcriptome profiling, secretome characterization, and functional enzymatic activity. We were able to identify a peritoneum-specific fibroblast population that increases in response to different types of damage-inducing peritoneal pathologies, including metastasis. These fibroblasts are characterised by the IGFBP2-dependent expression of CD38, which mediates extracellular non-canonical adenosinergic activity and contributes to the suppression of macrophages and T cells. Importantly, peritoneal fibroblasts promoted the growth and invasiveness of tumour cells in a xenograft mouse model of peritoneal metastasis, highlighting their pro-tumorigenic role. Their specific gene signature was associated with poor prognosis in a dataset of 51 patients suffering from colorectal peritoneal metastasis. This study revealed that the CPM is infiltrated by a peritoneal fibroblast subtype, which is absent in healthy tissue, but also observed in benign peritoneal diseases. Given the limited therapeutic options for these patients, these pro-tumorigenic peritoneal fibroblasts could represent an attractive target for inhibiting the peritoneal spread of tumour cells.

Background: Cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) increases survival in peritoneal carcinomatosis, but complications may affect the long-term prognosis. We aimed to evaluate the postoperative evolution after CS + HIPEC, the appearance of adverse outcomes, and the associated risk factors. Methods: This was a retrospective observational study evaluating clinical practice in patients undergoing CS + HIPEC from 2016 to 2023 in a tertiary-level university hospital. The pre-, intra-, and postoperative variables were collected. The postoperative evolution, the appearance of postoperative complications, and the mortality were analyzed according to the perioperative data. Results: In total, 62.3% of the patients developed some kind of complication. Renal failure was related to the length of surgery [mean difference (md) 111 min, 95% CI 11-210, p = 0.029], postoperative vasoactive support [Odds Ratio (OR) 3.4, 95% CI 1.1-10.6, p = 0.033], and non-invasive mechanical ventilation (OR 5.5, 95% CI 1.5-20.5, p = 0.007). Respiratory failure was associated with renal replacement therapies (OR 13.8, 95% CI 1.3-143.9, p = 0.006), postoperative creatinine (md 0.27 mg·dL-1, 95% CI 0.1-0.4, p = 0.001), and C-reactive protein (md 33.5 mcg·L-1, 95% CI 0.1-66.8, p = 0.049). Infectious complications were related to the length of surgery (md 84 min, 95% CI 12-156, p = 0.024), non-invasive mechanical ventilation (OR 4.4, 95% CI 1.2-16.1, p = 0.018), and renal replacement therapies (OR 11.6, 95% CI 1.1-119.6, p = 0.012). The hospital stay was longer in patients with complications (md 14.8 ± 5.5 days, 95% CI 3.8-25.8, p = 0.009). The mortality rate at 12 months was 15.6%. The mortality risk factors were the preoperative hemoglobin (md -1.7 g·dL-1, 95% CI -2.8--0.7, p = 0.001) and creatinine (md -0.12 mg·dL-1, 95% CI -0.21--0.04, p = 0.007) and the postoperative hemoglobin (md -1.15 g·dL-1, 95% CI 0.01-2.30, p = 0.049) and C-reactive protein (md 54.6 mcg·L-1, 95% CI 18.5-90.8, p = 0.004). Intraoperative epidural analgesia was found to be a protective factor for 12-month mortality (OR 0.25, 95% CI 0.07-0.90 p = 0.027). A multivariate analysis performed after a univariate analysis showed that the only risk factor for overall mortality was not using intraoperative epidural analgesia. Conclusions: CS + HIPEC led to a high incidence of postoperative complications, but the occurrence of complications did not seem to affect postoperative survival.

Chemotherapy of lethal colorectal peritoneal metastases (PM) is notoriously challenged by poor drug delivery efficiency in PM tumors. Inspired by the histopathological examinations of PM tumors from colon cancer patients, a C[RGDfK] peptide-modified bioinspired lipoprotein (R-BLP) system was optimized from 8 formulations with profound penetrating ability in PM tumors of colorectal cancers. Then, a chemotherapeutic 7-ethyl-10-hydroxy-camptothecin (SN38)-loaded R-BLP (termed SR-BLP) was designed to promote their penetration in PM tumors and improve the chemotherapeutic efficacy. In CT26-induced PM models, SR-BLP exhibited better penetration profiles in PM tumors over a counterpart liposomal formulation. SR-BLP treatment produced an 80.03% suppression of PM incidence with obvious DNA damage and topoisomerase I (TOP I) downregulation and caused a 1.78-fold prolongation of survival time. Therefore, the histopathological features-inspired R-BLP provides an encouraging tumor-penetrating delivery platform for the effective chemotherapy of colorectal PM.

Tumours of the appendix - a vestigial digestive organ attached to the colon - are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity - wherein the potential misclassification of appendiceal tumours as malignancies of the colon and ovaries also increases. Notwithstanding these diagnostic difficulties, our understanding of appendix carcinogenesis has advanced in recent years. However, there persist considerable challenges to accelerating the pace of research discoveries towards the path to improved treatments and cures for patients with this group of orphan malignancies. The premise of this Expert Recommendation article is to discuss the current state of the field, to delineate unique challenges for the study of appendiceal tumours, and to propose key priority research areas that will deliver a more complete picture of appendix carcinogenesis and metastasis. The Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation Scientific Think Tank delivered a consensus of core research priorities for appendiceal tumours that are poised to be ground-breaking and transformative for scientific discovery and innovation. On the basis of these six research areas, here, we define the first 'cells to society' research framework for appendix tumours.

Management of peritoneal surface malignancy (PSM) is complex and requires care at a PSM center. Despite the reported benefit of cytoreductive surgery (CRS)/ hyperthermic intraperitoneal chemotherapy (HIPEC) across PSM primaries, the uptake nationwide is low. The reasons are multifaceted and related to factors that disproportionately impact racial and ethnic minorities, rural residents, and other socially vulnerable patient populations. There are significant misperceptions of CRS/HIPEC in the treatment of PSM and the potential benefit for appropriately selected patients. Much work is needed to improve patient and provider education and to expand the reach of expert PSM management to vulnerable patients.

Peritoneal metastases from colorectal cancer (PMCRC) present a complex treatment challenge requiring multidisciplinary expertise. Significant controversy exists regarding the optimal management of PMCRC patients. In this article, we seek to review the currently available evidence and discuss key components of patient workup, treatment, and management.

Appendiceal neoplasms and colorectal cancer have a propensity to develop peritoneal metastases. Despite advancements in systemic therapy and surgical management, the development and management of peritoneal metastases remains a challenging problem. Utilization of adjuvant or prophylactic hyperthermic intraperitoneal chemotherapy has been described, with varying quality of data and reported outcomes. The utilization of prophylactic or adjuvant hyperthermic intraperitoneal chemotherapy in patients with appendiceal neoplasms and colorectal cancer remains an active area of exploration.

Cytoreductive surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) candidates often have extraperitoneal abdominal disease. Current expert peritoneal surface malignancy (PSM) guidelines recommend that the presence of extraperitoneal disease is a contraindication to CRS-HIPEC.

We conducted a retrospective review of our institutional appendiceal and colorectal CRS-HIPEC registries. Two study cohorts were constructed: (1) cytoreduction with extraperitoneal abdominal disease, and (2) cytoreductions limited to peritoneal structures alone. The primary study outcome was survival. Subgroup analysis was based on the primary tumor and completeness of cytoreduction.

Overall, 864 CRS-HIPEC cases were evaluated, consisting of 578 appendiceal primaries and 286 colorectal cancers. The extraperitoneal cohort included 101 patients, with 763 patients in the non-extraperitoneal group. The median follow-up time was 13.18 years. The main analysis showed no significant differences in survival times. For overall survival (OS) there was a mean OS time of 5.87 years and a median OS time of 4.43 years for extraperitoneal cytoreductions compared with a mean of 5.90 years and a median of 4.76 years for non-extraperitoneal cytoreductions (p = 0.955). Five-year OS rates did not differ at 49.1% versus 49.5% (odds ratio [OR] 1.036, 95% confidence interval [CI] 0.671-1.597, p = 0.874). Disease-free survival (DFS) times showed a mean of 4.40 years and a median of 1.93 years for extraperitoneal cases versus a mean of 5.44 years and a median of 3.05 years for non-extraperitoneal cases (p = 0.210). Five-year DFS rates also showed no differences (OR 0.894, 95% CI 0.476-1.681, p = 0.728). No significant differences in progression-free survival (PFS)Pp times (p = 0.061) were reported. Multivariate Cox regression analysis indicated that extraperitoneal CRS was not an independent predictor of OS (hazard ratio [HR] 1.281, 95% CI 0.885-1.854, p = 0.190), DFS (HR 1.087, 95% CI 0.694-1.701, p = 0.716), or PFS (HR 0.650, 95% CI 0.243-1.738).

We conducted the largest analysis evaluating extraperitoneal cytoreductions, with no significant differences in almost all survival outcomes. We propose that the presence of extraperitoneal abdominal disease is not a contraindication to proceeding with CRS-HIPEC.

Peritoneal surface malignancies (PSMs) represent a biologically diverse group of cancers that range from primary peritoneal mesothelioma to metastatic gastrointestinal cancers. Because of the heterogenous nature of PSM, there is a large gap in molecular characterization of these cancers. This article reviews the underlying molecular and genetic mechanisms for PSM.

Rectal cancer is universally considered a different disease entity as compared to colon cancer, except when dealing with colorectal peritoneal carcinomatosis (PC), in which the two cancers are deemed as the same one. The present study aims to investigate the influence of primary tumor location (colon vs. rectum) on oncologic outcomes in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases. Data from three referral centers undergoing CRS plus HIPEC for PC of colorectal origin were prospectively collected. The primary outcomes were overall survival (OS) and disease-free survival (DFS) according to primary tumor location (colic vs. rectal). Univariate and multivariate analyses were performed using the Cox proportional hazard model first on the total number of patients. Then, a propensity score matching using the nearest-neighbour method with a 1:1 ratio was performed. The study included 167 patients: 126 colic and 41 rectal PC. After propensity score matching, rectal primary tumor location was independently predictive of a lower DFS (HR 1.91; 95%CI 1.06-3.45; p = 0.031) but not of a lower OS (HR 1.12; 95%CI 0.57-2.21; p = 0.73). Post-matching 3-year DFS rates were 49.2% (95%CI 34,3-70,5%) and 19.4% (95%CI 9,4-40,2%) for colic and rectal PC, respectively. The present study shows a significantly worse DFS for rectal cancer PC undergoing CRS and HIPEC compared to colon cancer PC, suggesting a possible need for dedicated pathways for rectal PC patients and posing a question for rectal PC to be considered as a unique disease entity.

Appropriate assessment of disease burden in patients with peritoneal surface malignancy (PSM) is critical for treatment decision-making, and conventional cross-sectional imaging (computed tomography and/or MRI) often underestimates burden of disease. Advances in imaging for PSM include novel functional imaging modalities that target cells unique to the tumor microenvironment. Novel alternative methods of diagnosis and disease monitoring are also potentially applicable to management of PSM. These include forms of "liquid biopsy" targeting circulating tumor DNA. Novel regional therapies include both new therapeutic agents (immune-based and nanoparticle-based), as well as new methods of delivery such as pressurized intraperitoneal aerosolized chemotherapy.

About a quarter of patients with locally advanced colon cancer (pT4) develop locoregional recurrence, including peritoneal metastases. The aim of this individual patient data meta-analysis (IPDMA) was to evaluate the efficacy of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) with regard to reducing the locoregional recurrence rate in the overall population and high-risk subgroups of patients with locally advanced colon cancer.

A systematic literature search was conducted in July 2024 to identify RCTs on adjuvant HIPEC in addition to routine adjuvant systemic chemotherapy in locally advanced colon carcinoma. An IPDMA was performed, with the locoregional recurrence rate as the primary endpoint and disease-free survival (DFS) and overall survival (OS) as secondary endpoints.

The search identified two trials (COLOPEC and HIPECT4). Individual patient data were pooled for 386 patients, of whom 189 patients received adjuvant HIPEC and 197 patients constituted the control group. The median follow-up was 36 (interquartile range 32-60) months. A modified intention-to-treat analysis showed a 36-month locoregional recurrence rate of 16.0% for HIPEC patients and 21.2% for control patients (P = 0.295). Predefined subgroup analyses revealed a significant reduction in locoregional recurrence after HIPEC in patients with right-sided tumours (HR 0.56 (95% c.i. 0.48 to 0.67)) (P < 0.001). No significant differences in survival were found for the overall study population; low event rates in subgroups did not allow for survival analyses.

Adjuvant HIPEC significantly reduced the locoregional recurrence rate in right-sided locally advanced colon cancer, but not in the overall study population. Definitive conclusions on DFS and OS require longer follow-up.

Colorectal cancer (CRC) is the third most common cancer type and one of the leading causes of cancer-related death worldwide. The treatment of advanced metastatic CRC relies on classical chemotherapy combinations (5-fluorouracil, oxaliplatin or irinotecan). However, their use is limited by the emergence of resistance mechanisms, including to oxaliplatin. In this context, we recently showed that the combination of oxaliplatin and ataxia telangiectasia and Rad3-related protein inhibition (VE-822) is synergistic and may have a potential therapeutic effect in metastatic CRC management.

In this study, we investigated the role of the VE-822+oxaliplatin (Vox) combination on the immune response and its potential synergy with an anti-programmed-cell Death receptor-1 (PD-1) antibody. We used cell lines and organoids from metastatic CRC to investigate in vitro Vox efficacy and orthotopic syngeneic mouse models of metastatic CRC to assess the efficacy of Vox+anti-PD-1 antibody and identify the involved immune cells.

The Vox+anti-PD-1 antibody combination completely cured tumor-bearing mice and protected them from a rechallenge. Vox was associated with a reduction of tumor-infiltrated neutrophils, CD206+ macrophages and regulatory T cells. Vox also induced a deep depletion of blood neutrophils. The increased bone marrow granulopoiesis failed to compensate for the Vox-mediated mature neutrophil depletion. Neutrophil depletion using a mouse recombinant anti-Ly6G antibody partially mimicked the Vox effect on the tumor microenvironment, but to a lower extent compared with the Vox+anti-PD-1 antibody combination. Vox, but not neutrophil depletion, led to the emergence of an Ly6C+ PD-1+ CD8+ T-cell population in the blood and spleen of tumor-harboring mice. These cells were proliferating, and expressed IFN-γ, CD62L, CXCR3 and Eomes. Moreover, the proportion of tumor antigen-specific T cells and of CD122+ BCL6+ T cells, which shared phenotypic characteristics with stem-like CD8+ T cells, was increased in treated mice.

Our work strongly suggests that the Vox+anti-PD-1 antibody combination might significantly improve survival in patients with metastatic and treatment-refractory CRC by acting both on cancer cells and CD8+ T cells.

The aim of this study was to determine the incidence, treatment patterns, survival and factors associated with curative treatment in colorectal cancer patients with combined liver and peritoneal metastases using Dutch population-based data.

Data from the Netherlands Cancer Registry were used. All patients diagnosed with synchronous isolated peritoneal and liver metastasized colorectal adenocarcinoma between January 1, 2015 and December 31, 2021 were included. Multivariable regression analyses were performed to identify factors associated with receiving curative treatment. Survival rates were calculated for patients undergoing palliative and curative treatment separately.

Of 14627 patients with colorectal adenocarcinoma in the study period, 927 patients (6.3 %) had isolated liver and peritoneal metastases and were evaluated in this study. Mean age was 66.9 years, non-mucinous and non-signet-ring cell adenocarcinomas were most prevalent (89.0 %) and tumors were mostly located in the colon (92.1 %). Patients were treated with best supportive care (n = 254, 27,4 %), palliative treatment (n = 618, 66,7 %) or curative treatment (n = 55, 5,9 %). Median OS was 1.5 months, 11.3 months, and 32.6 months, respectively. Multivariable analysis showed that younger age (OR 0.95, p < 0.001) and up to 3 liver metastases (OR 0.13, p < 0.001) are positively associated with receiving curative treatment.

This population-based study provides a comprehensive overview of the incidence and treatment of patients with synchronous colorectal liver and peritoneal metastases. It shows that in a highly selected group of patients, curative treatment is associated with better overall survival.

Traditionally there has been a nihilistic approach towards patients with pulmonary metastases arising from colorectal cancer. However, emerging evidence highlights the benefit of curative intent treatment. Given the established individual roles of pulmonary metastectomy and CRS/HIPEC in the treatment of colorectal pulmonary and peritoneal metastases, respectively, we decided to combine these modalities and determine whether pulmonary metastases really influence the outcomes of curative intent treatment in CRC patients with peritoneal metastases.

This was a retrospective study of a prospectively maintained database of CRC patients with peritoneal metastases undergoing CRS and HIPEC with curative intent from Jan 1, 2005 to Aug 1, 2018. Patients were divided into two groups of without pulmonary metastases and with pulmonary metastases. Patients were followed up for a median 40.8 months.

Of total 455 patients 19 had pulmonary metastases. The median RFS and OS of all patients was 14.26 months (95 % CI:12.71-16.2) and 56.96 months (95 % CI: 47.73-77.79) respectively. Median RFS and OS of patients with and without pulmonary metastases was 12 & 49.8 months and 14.4 & 57.9 months, respectively. On multivariate analysis, PCI, CC-0 rate, CEA, signet ring histology and retroperitoneal lymph node metastases significantly affected the OS. Presence of pulmonary metastases did not significantly affect the RFS or OS.

There has always been a skepticism in the management CRC with PM and extraperitoneal disease, especially pulmonary metastases with curative intent. Our study demonstrates that CRS and HIPEC improves OS in such patients and pulmonary metastases per se do not influence the outcomes of disease. Nevertheless, further prospective and multi centric studies are required to validate these findings.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) enable effective management of colorectal and appendiceal peritoneal metastases (CAPM) despite high morbidity. This study aimed to evaluate the role of repeat diagnostic laparoscopy (rDL) after systemic ± intraperitoneal chemotherapy in the management of initially unresectable CAPM.

This retrospective cohort study included 70 consecutive patients with CAPM who underwent initial diagnostic laparoscopy (iDL). Patients with inoperable or equivocal CAPM underwent chemotherapy followed by rDL to assess the treatment response and possibility of conversion to CRS and HIPEC.

Cytoreductive surgery was deemed feasible for 29 patients and unlikely or equivocal for 41 patients based on iDL. Of the 29 resectable patients, 24 successfully underwent CRS and HIPEC after neoadjuvant chemotherapy. Among the 41 patients initially considered unresectable, 16 were deemed operable based on rDL after chemotherapy, and CRS and HIPEC were achieved for 14 patients (conversion). The median peritoneal cancer index was significantly reduced after chemotherapy for the 14 "conversion" patients, from 16 based on iDL to 11 based on rDL (p < 0.05). The conversion rate was 34% (14/41), with a 5-year survival rate of 14%. Treatment with CRS and HIPEC was achieved for 38 of 45 patients deemed operable based on either iDL or rDL (worst-case estimated positive predictive value, 84%).

Diagnostic laparoscopy is useful in predicting the likelihood of achieving CRS for patients with CAPM. Despite inoperability based on iDL, patients should be considered for rDL after chemotherapy to assess the possibility of conversion to CRS and HIPEC.

Background/Objectives: Hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) has been reported to improve survival in patients with peritoneal carcinomatosis. This study aimed to investigate the morbidity and mortality rates of CRS with HIPEC in patients with ovarian cancers. Methods: We retrospectively reviewed the medical records of patients who underwent CRS with HIPEC for ovarian cancer from January 2013 to July 2021 at two tertiary institutions. The morbidities and mortalities that occurred within 30 days after HIPEC and the clinical and operative factors related to morbidities were investigated. Results: A total of 155 procedures in 151 patients were included in this study. The median age was 55 years and the median score of the peritoneal carcinomatosis index was eight points. Morbidities of grade ≥3 within 30 days of HIPEC occurred in 18 patients (11.6%). The most common severe morbidity was wound infection (3.2%), followed by pleural effusion (1.9%) and postoperative hemorrhage (1.9%). Within the 30-day postoperative period, there were no reported mortality cases. There were statistical differences in age, length of stay, peritoneal carcinomatosis index, bowel resection, operation time, and completeness of cytoreduction between the patients and severe morbidity. However, in the multivariate logistic analysis, none of the factors showed a statistically significant relationship with the occurrence of severe morbidity. Conclusions: The morbidity and mortality rates of CRS with HIPEC in gynecologic cancer patients were relatively low compared to those in previous reports. Further studies about the possible risk factors are needed.

Selection of suitable candidates for intraoperative tumour detection and cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is important for improving outcomes for patients with colorectal peritoneal metastases. Previous research demonstrated the use of single-photon emission computed tomography (SPECT), intraoperative radiodetection, and near-infrared fluorescence (NIRF)-guided surgery with a dual-labelled 111In-labelled dodecane tetra-acetic acid (DOTA)-labetuzumab-IRDye800CW tracer to detect peritoneal metastases before operation. The aim of this study was to validate these results.

A single-centre phase II study was conducted to evaluate the safety and feasibility of 111In-labelled DOTA-labetuzumab-IRDye800CW in patients with colorectal peritoneal metastases undergoing CRS-HIPEC. SPECT/computed tomography (CT) was undertaken before surgery, after intravenous administration of 10 mg 111In-labelled DOTA-labetuzumab-IRDye800CW (mean 101.25 MBq). During surgery, radiodetection and NIRF imaging were used for tumour detection. Adverse events were assessed, and tumour-to-background ratios (TBRs) and peritoneal cancer index scores were analysed.

Seven patients were included. No study-related severe adverse events were reported. Imaging before surgery revealed previously undetected metastases in one patient. The mean(standard deviation, s.d.) SPECT/CT peritoneal cancer index score was 3(2), and the intraoperative score was 14(7) (P = 0.032). A total of 52 lesions were removed during CRS, of which 37 were malignant. With NIRF imaging, 34 (92%) of 37 malignant lesions were detectable. Of 52 fluorescent lesions, 4 were false-positive. Mean(s.d.) fluorescence TBR was 3.4(1.8) and mean radiodetection TBR was 4.4(1.4).

This study confirmed the safety and feasibility of multimodal image-guided surgery in patients with peritoneal metastases.

Consensus regarding the hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer (CRC) regimen remains elusive. In this study, patient-derived tumor organoids from CRC were utilized as a preclinical model for in vitro drug testing of HIPEC regimens commonly used in clinical practice. This approach was used to facilitate the clinical formulation of HIPEC.

Tumor tissues and corresponding clinical data were obtained from patients diagnosed with CRC at the Sixth Affiliated Hospital of Sun Yat-Sen University. Qualified samples were cultured and passaged. We aimed to assess the sensitivity of in vitro hyperthermic perfusion using five different regimens, i.e. mitomycin C, mitomycin C combined with cisplatin, mitomycin C combined with 5-fluorouracil, oxaliplatin, and oxaliplatin combined with 5-fluorouracil.

Tumor organoids obtained from 46 patients with CRC were cultured, and in vitro hyperthermic perfusion experiments were conducted on 42 organoids using five different regimens. The average inhibition rate of mitomycin C was 85.2% (95% confidence interval [CI] 80.4-89.9%), mitomycin C combined with cisplatin was 85.5% (95% CI 80.2-90.7%), mitomycin C combined with 5-fluorouracil was 65.6% (95% CI 59.6-71.6%), oxaliplatin was 37.9% (95% CI 31.5-44.3%), and oxaliplatin combined with 5-fluorouracil was 40.7% (95% CI 33.9-47.5%).

In vitro hyperthermic perfusion demonstrates that the inhibition rate of mitomycin C, both alone and in combination with cisplatin, surpasses that of the combination of mitomycin C with 5-fluorouracil and oxaliplatin. In clinical practice, the combination of mitomycin C and cisplatin can be regarded as the optimal choice for HIPEC in CRC.

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.

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.

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.

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.

Colorectal cancer (CRC) is a common malignancy with the propensity to metastasize. Common sites of metastasis include the liver, lungs, and peritoneum, with peritoneal metastases (PMs) having the worst prognosis. Unfortunately, systemic chemotherapy is often less effective in the treatment of PMs. Therefore, removal of all visible tumor via cytoreductive surgery along with intraperitoneal (IP) therapies has been used.

A comprehensive review of the literature was conducted using MEDLINE/PubMed and Web of Science with an end date of September 1, 2024, regarding cytoreductive surgery and heated IP chemotherapy for CRC PMs.

Recent studies have called into question the utility of IP chemotherapy in the treatment of CRC PMs. However, regardless of IP chemotherapy, cytoreductive surgery has demonstrated an additional survival benefit for patients with PM secondary to CRC.

This study reviews the pathophysiology of CRC PM, the current treatment paradigms, and a pathway for improving outcomes in patients with CRC PM.

Colorectal liver metastases (CRLM) are a major indication for liver surgery in Europe, highlighting the need for standardized knowledge and training in surgical oncology. The European Society of Surgical Oncology (ESSO) has updated its core curriculum to provide a structured framework for education. Previous publications have addressed pancreatic, hepatocellular, and biliary tract cancers to support candidates preparing for the European Board of Surgery Qualification (EBSQ) exams in Surgical Oncology and Hepato-Pancreato-Biliary Surgery. However, a dedicated guide for CRLM remains absent. This article aims to fill that gap by offering a structured reference on CRLM, covering epidemiology, staging, genetics, and diagnosis of metastatic colorectal cancer. It also outlines multidisciplinary treatment strategies, including systemic, surgical, interventional, and palliative approaches. A structured literature review was conducted using PubMed to identify the most updated (inter)national management guidelines, prioritizing recent multicentre studies, systematic reviews, and meta-analyses published from January 2020 to January 2025. By bridging the gap between the ESSO core curriculum and detailed subspecialty training, this guide provides an essential resource for hepatobiliary surgeons and surgical oncologists. It serves as a valuable tool for those preparing for board examinations while promoting a standardized approach to CRLM education and management across Europe.

Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment concept for highly selected patients with peritoneal metastases and primary tumors (PMT). A challenge from the perspective of hospitals is the cost intensity of this promising multimodal treatment option.

Which factors influence the cost and revenue structure of CRS/HIPEC treatment in the current diagnosis-related group (DRG) system according to § 17b of the German Hospital Financing Act (KHG)?

The database for this analysis was constituted by all patients treated with combined CRS/HIPEC at a certified tumor center between 2017 and 2021. The statistical analysis performed was descriptive, using two-sample and multisample comparisons (ANOVA) as well as linear correlation and regression analyses.

The total length of hospitalization for 173 patients was on average 16.1 days and the average length of stay in the intensive care unit was 2.2 days. Postoperative complications occurred in 110 (63.6%) patients. The average DRG revenue obtained was € 21,658.48. The total costs for the combined CRS/HIPC treatment amounted to an average of € 23,764.77 and were therefore on average € 2106.29 (8.86%) higher than the DRG revenue granted for the treatment. The length of stay in the intensive care unit and the total length of hospitalization correlated positively with the treatment costs and DRG revenue.

This study presents key factors influencing the cost and revenue structure of CRS/HIPEC and illustrates that this promising surgical treatment approach is relevantly underfunded by the German DRG system. A reform of the current DRG system with special consideration of highly complex oncological treatment concepts is therefore recommended.