Peritoneal disease can be classified as either benign or malignant in nature. Malignant peritoneal disease can be further considered as either primary or secondary in origin. Primary peritoneal malignancy includes peritoneal mesothelioma, serous carcinoma, and desmoplastic small round cell tumour. Peritoneal carcinomatosis is the most commonly encountered secondary malignant peritoneal disease, typically of ovarian, gastric, colorectal, pancreatic, small bowel neuroendocrine, or breast origin. Others include peritoneal lymphomatosis and sarcomatosis. Benign peritoneal pathology may mimic malignant disease. Differentiating benign from malignant peritoneal pathology can be challenging, but is critical to guide appropriate care and avoid unnecessary intervention. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) offers potentially curative treatment for patients with peritoneal carcinomatosis, pseudomyxoma peritonei, and peritoneal mesothelioma. For such patients, the radiologist provides crucial pre-operative information highlighting sites of disease involvement, particularly for sites which are challenging to assess at laparotomy or laparoscopy, including the hepatic dome, subdiaphragmatic space and mesenteric root. The radiologist is also essential to identify potential contraindications to surgery, as well as interpreting normal post-operative appearances, complications and assessing for disease recurrence.

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.

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.

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.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is increasingly performed in young patients with peritoneal surface malignancies. Important quality of life (QoL) questions arise; however, there is limited research on fertility experiences in young women with carcinomatosis or following CRS/HIPEC.

Retrospective review of a prospective database evaluating women less than 45 ys who underwent CRS/HIPEC at the University of Pittsburgh Medical Center from January 1998 to 2020. Eligible patients were contacted for a telephone-based interview. Themes regarding fertility counseling, childbearing, and patient-identified issues were investigated.

A total of 28 of 29 women who met inclusion criteria participated. The majority had appendiceal primary (16/28). Most received Mitomycin C intraperitoneal chemotherapy (26/28) with an average Peritoneal Cancer Index of 8 (0-39). Almost half of the women (43%) desired fertility discussion. Although this conversation happened more often in younger patients, 75% were over the age of 35 ys at time of initial HIPEC. Less than half were offered fertility counseling. When fertility conversations occurred, many felt that they were insufficient. In addition to fertility, women cited lack of support on postprocedure hormonal and associated QoL changes.

As we treat younger females with CRS/HIPEC, we must provide support for age-appropriate QoL issues including fertility and surgical menopause.

disease burden (PCI), completeness of cytoreduction or histological features, are known to influence survival after CRS-HIPEC for colorectal peritoneal metastases (CPM). However, there is still debate about influence of CPM onset. The aim of this study is to determine the impact of CPM onset on oncological outcomes after CRS-HIPEC.

all patients with CPM scheduled for CRS-HIPEC at one reference center between December 2007 and September 2022 were included. s-PM were defined as those diagnosed at primary disease treatment; m-PM were considered those diagnosed during follow-up. Survival outcomes and recurrence rates were compared using a pragmatic analysis.

125 patients with s-CPM and 170 patients with m-CPM were analyzed. Median follow-up was 58.6 and 50.6 months in s-CPM and m-CPM groups(p = 0.11). Complete cytoreduction (CCS-0/-1) rates were comparable: 84 % s-CPM vs. 88.2 % m-CPM(p = 0.190). Overall survival (OS) was significantly shorter in s-CPM: 24.7 vs. 46.6 months (p = 0.024). Conversely, median disease-free survival was similar in both groups, 10 months vs. 11 months(p = 0.155). Patients in the s-CPM group presented more pN+(p = 0.001), higher histologic grade(p = 0.007) and PCI(p = 0.04), and higher rate of concurrent liver metastases(p = 0.004). RAS/BRAF gene mutations and microsatellite instability did not differ significantly. Perioperative chemotherapy regimens and tolerance were also similar.

despite s-CPM being associated with impaired OS after CRS-HIPEC, the onset of PM was not found to be an independent determinant for survival. High-risk molecular and histological features strongly influence oncological outcomes after CRS-HIPEC. This is valuable data that could aid in preoperative patient selection process for CRS-HIPEC.

Peritoneal carcinomatosis presents significant treatment challenges. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) offers a promising therapeutic approach. Patient selection remains critical, and the role of age as an exclusion criterion requires further investigation. This study evaluates whether age influences postoperative outcomes in CRS-HIPEC patients.

A retrospective review of a prospective comprehensive database of 271 CRS-HIPEC procedures performed between 2018 and 2023 was conducted. Logistic regression assessed the relationship between age and postoperative outcomes. Age groups (18-44, 45-69, ≥70 years) were compared based on demographic data, primary tumor site, Peritoneal Cancer Index scores, and key outcome measures.

Across the different age groups, there were no significant differences in PCI scores, recurrence, disease-free survival, 30-day morbidity, or mortality. Length of stay was longer in older patients (p = 0.009). Patients aged ≥70 had higher readmission rates (p = 0.041) and were more often discharged to transitional care facilities (p = 0.001). Older patients were also more likely to experience Clavien-Dindo grade III or higher complications (p = 0.008). Logistic regression confirmed these findings. Continuous age analysis yielded similar results and revealed significant differences in race and primary organ involvement.

Age is not a significant predictor of 30-day morbidity, mortality, or survival outcomes in patients undergoing CRS-HIPEC. However, older patients require closer attention to discharge planning and readmission risk management. This study highlights the importance of comprehensive patient assessment beyond age and underscores the need for further research to better understand factors influencing outcomes in this population.

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).

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.

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.

Elevation of several preoperative tumor markers is associated with poor prognosis and increased risk of open-close. CA72-4 deserves increased attention.

Open cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a therapeutic option for the management of malignancies with peritoneal carcinomatosis and of peritoneal origin. Robotic surgery shows promise as a minimally invasive approach for select patients. We aimed to evaluate the differences in outcomes between robotic versus open CRS/HIPEC and hypothesized less morbidity and faster recovery in the robotic approach group.

We conducted a retrospective cohort study from our HIPEC database including all tumor origins. We included patients aged 18-89 years who underwent CRS/HIPEC for curative intent at a single institution between January 1, 2017, and December 31, 2023. Patients were stratified by open versus robotic-assisted surgery. Mann-Whitney U and Fisher Exact tests were used to compare differences in patient characteristics and outcomes.

A total of 111 patients underwent CRS/HIPEC for curative intent, with 95 (85.6%) cases performed open and 16 (14.4%) robotically. The groups were demographically similar, except patients undergoing robotic CRS/HIPEC had a significantly higher median income ($83,845 vs. $70,519, p < 0.001). Rate of comorbidities and cancer type, including appendiceal, colorectal, and ovarian, were the same. The peritoneal carcinomatosis index and completion of cytoreduction score were similar between groups. Robotic approach was associated with statistically significant lower estimated blood loss (113 vs. 400 mL, p < 0.001) and postoperative transfusions (6.3% vs. 23.2%, p = 0.036). Total complications, readmission rates, and 30-day mortality were similar among groups, but the robotic group had a significantly shorter length of stay (5.5 vs. 9 d., p < 0.001).

Robotic CRS/HIPEC holds promise to decrease intraoperative blood loss, blood transfusions, and hospital stay while providing similar immediate postoperative outcomes in select patients. These results should be validated in the setting of a prospective trial and effects on long-term oncologic outcomes should be investigated.

Peritoneal metastases due to gastric adenocarcinoma (GCPM) carry a dismal prognosis. A promising treatment strategy is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), but clear eligibility criteria for GCPM are lacking. We sought to identify factors associated with overall survival (OS) following CRS-HIPEC for GCPM to help optimize patient selection and clinical outcomes.

In this single-center retrospective cohort study, we examined CRS-HIPEC outcomes for patients with GCPM between 2001 and 2021. After analyzing patient demographic, clinicopathologic, and perioperative variables, we applied multivariable Cox hazard models to assess factors associated with OS. We then assessed associations between baseline predictors and prognostically important variables using multivariable logistic regression.

We analyzed 55 patients with GCPM who underwent CRS-HIPEC. Median age was 54 years and 42% were female. Median peritoneal carcinomatosis index (PCI) was 8, and 75% of patients achieved a cytoreduction completeness score (CC score) of 0. Median progression-free survival (PFS) was 6.9 months, and median OS was 14.1 months. On adjusted analysis, a CC score > 0 (HR 2.3, p = 0.02) was significantly associated with worse OS. A peritoneal carcinomatosis index greater than 13 (OR 52.6, p = 0.001) and fewer lymph nodes (especially < 18) resected with the primary tumor (OR 0.86, p = 0.042) in the metachronous setting were significantly associated with incomplete macroscopic cytoreduction (CC score > 0).

We demonstrated that PCI > 13 and primary lymph nodes harvested < 18 in metachronous tumors are associated with CC score > 0, which in turn portends a worse OS. Although these results warrant prospective validation, they provide insight into improved selection of patients with GCPM for CRS-HIPEC.

We evaluated the occupational exposure levels of healthcare workers while conducting rotational pressurized intraperitoneal aerosol chemotherapy (RIPAC) using cisplatin in a large animal model.

We performed RIPAC using cisplatin in 6 female pigs and collected surface and air samples during the procedure. Surface samples were obtained from RIPAC devices and personal protective equipment (PPE) by wiping, and air samples were collected around the operating table. All samples were analyzed by inductively coupled plasma-mass spectrometry to detect platinum.

Among all surface samples (n=44), platinum was detected in 41 samples (93.2%) but not in all air samples (n=16). Among samples collected from RIPAC devices (n=23), minimum and maximum cisplatin levels of 0.08 and 235.09 ng/cm² were detected, mainly because of direct aerosol exposure in the abdominal cavity. Among samples collected from healthcare workers' PPE (n=21), 18 samples (85.7%) showed contamination levels below the detection limit, with a maximum of 0.23 ng/cm². There was no significant contamination among samples collected from masks, shoes, or gloves.

During the RIPAC procedures, there is a potential risk of dermal exposure, as platinum, a surrogate material for cisplatin, was detected at low concentration levels in some surface samples. However, the respiratory exposure risk was not identified, as platinum was not detected in the airborne samples in this study.

This manuscript reports the results of the Indian Network for Development of Peritoneal Surface Oncology and Indian Society of Peritoneal Surface Malignancies (INDEPSO-ISPSM) consensus that aimed to provide recommendations for some important aspects management of patients with colorectal peritoneal metastases (CPM) and address some issues unique to India.

The modified Delphi technique was used with two rounds of voting. There were 29 questions on nine main topics-the role of cytoreductive surgery (CRS), patient selection for CRS, preoperative workup, role of systemic chemotherapy (SC), CPM with other visceral metastases, molecular profile, hyperthermic intraperitoneal chemotherapy (HIPEC) and other modalities of intraperitoneal chemotherapy (IPC), prophylactic/preventive strategies, and surveillances after CRS. A consensus was achieved if anyone option received >70 votes (strong consensus >90%).

Forty-eight surgical (n = 41) and gastrointestinal (n = 7) oncologists were invited; 44 agreed to participate. The response rate was 95.4% (42/44) in round 1 and 93.1% (41/44) in round 2. Overall, a consensus was achieved on 23/29 (79.3%) questions (strong consensus on 6/29 [20.6%]). The panel strongly recommended considering surgery for limited CPM with limited liver metastases (92.5%), not altering the surgical approach in patients with KRAS mutations (91.67%), and limiting the use of IPC for unresectable CPM outside clinical trials (95%). Adjuvant SC was recommended for all patients undergoing CRS (89.47%). CRS is a therapeutic option for selected patients with CPM including those with metachronous CPM (79.49) and signet ring cell cancers (76.92%). HIPEC was recommended outside clinical trials only for patients with peritoneal cancer index 11-15(80%).

The panel recommended CRS for most indications but was very selective in recommending HIPEC and IPC outside clinical trials. These recommendations should be a useful resource in clinical decision making for clinicians treating CPM in India and regions with a similar sociodemographic background.

The peritoneal metastasized colorectal cancer (pmCRC) represents a serious health problem worldwide with a special emphasis in the developed countries. Several guidelines recognize the role of multimodal therapy consisting of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pmCRC. New data suggests that some other factors, eg, tumor biology, immune profile, neoadjuvant chemotherapy may play a predictive role for the oncological outcome of these patients.

The presence at diagnosis, or development of, colorectal peritoneal metastases (CPM) is common in colorectal cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) show promising results in selected patients with CPM. The current study aimed to describe oncologic outcomes of patients with CPM, focusing on recurrence patterns and risk factors for adverse events.

We conducted a retrospective review of patients with CPM treated by CRS and HIPEC at a single institution between 2000 and 2021.

A total of 555 patients were included, of whom 480 (86.5%) had complete cytoreduction, with a median age of 59 years and median Peritoneal Cancer Index (PCI) of 6. Following complete cytoreduction, 5-year overall survival (OS) and disease-free survival (DFS) were 51% and 31%, respectively. In multivariable Cox regression, PCI >6 (hazard ratio [HR] 2.25), pathological node positivity (pN+; HR 1.94), and perineural invasion (HR 1.85) were associated with decreased OS, while PCI >6, pN+, and previous systemic metastases resulted in reduced DFS. Overall, 284 (62%) patients developed recurrence, of whom 97 (34%) had local recurrence (LR), 100 (35%) had systemic recurrence (SR), and 87 (31%) had combined recurrence (5-year OS: 49.3%, 46%, and 37.4%, respectively). Mutated KRAS (mKRAS) was associated with lower 5-year OS (55.8%) and DFS (27.9%) compared with wild-type KRAS (wtKRAS; 70.7% and 37.6%, respectively). In multivariable analyses, mKRAS was related to decreased OS (HR 1.82), DFS (HR 1.55), and SR (OS 1.89), but not to LR.

Complete cytoreduction results in good survival outcomes for patients with CPM. Burden of peritoneal disease and tumor biology are the main predictors of survival. Patients with mKRAS are a high-risk cohort, with increased probability of SR and reduced survival.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) consists of the administration of aerosolized chemotherapy into the abdominal cavity of patients suffering from peritoneal carcinomatosis. Our aim was to review the evidence supporting PIPAC in patients with peritoneal carcinomatosis from colorectal cancer.

A systematic review was performed in accordance with the 2020 PRISMA guideline. MEDLINE and CENTRAL were searched using combinations of terms including "Peritoneal carcinomatosis", "Peritoneal metastasis", "PIPAC", "Pressurized intraperitoneal aerosol chemotherapy" and "Colorectal cancer". Original studies, in English, including patients treated with PIPAC for colorectal peritoneal carcinomatosis, were considered eligible. Case reports, non-English or French language articles and secondary analyses were excluded.

A total of 385 articles were screened and 374 articles were excluded, leaving 11 publications for inclusion in the qualitative analysis. The included studies totalized 949 patients who received PIPAC for peritoneal carcinomatosis due to colorectal cancer. The median peritoneal carcinomatosis index (PCI) ranged from 10 to 31. In all studies, the complete PIPAC protocol was achieved with an average of two to three 3 PIPAC sessions per patient. Oxaliplatin (OX) was used as a chemotherapeutic agent in all studies and could be associated with intravenous 5-FU and leucovorin. Most post-operative adverse events were recorded as mild to moderate with no intraoperative complications. Only four studies reported a decrease in the average PCI score for 50% of the patients. Median overall survival ranged from 8 to 37.8 months. Quality of life indicators were stable between PIPAC-OX cycles with a small but not statistically significant trend of improvement of most functional scales.

PIPAC for peritoneal carcinomatosis from colorectal origin is feasible, safe and tolerable. Its impact on survival outcomes or quality of life remains to be demonstrated by randomized trials.

This manuscript reports the results of an international consensus on technologies of hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) performed with the following goals: To provide recommendations for the technological parameters to perform HIPEC. To identify the role of heat and its application forms in treating peritoneal metastases. To provide recommendations regarding the correct dosimetry of intraperitoneal chemotherapy drugs and their carrier solutions. To identify for each intraperitoneal chemotherapy regimen the best dosimetry and fractionation. To identify areas of future research pertaining to HIPEC technology and regimens. This consensus was performed by the Delphi technique and comprised two rounds of voting. In total, 96 of 102 eligible panelists replied to both Delphi rounds (94.1%) with a consensus of 39/51 questions on HIPEC technical aspects. Among the recommendations that met with the strongest consensus were those concerning the dose of HIPEC drug established in mg/m2, a target temperature of at least 42°C, and the use of at least three temperature probes to pursue hyperthermia. Ninety minutes as the ideal HIPEC duration seemed to make consensus. These results should be considered when designing new clinical trials in patients with peritoneal surface malignancies.

Despite advancements in early detection and treatment in developed countries, colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths worldwide. Conventional chemotherapy, a key option for CRC treatment, has several drawbacks, including poor selectivity and the development of multiple drug resistance, which often lead to severe side effects. In recent years, the use of polysaccharides as drug delivery systems (DDSs) to enhance drug efficacy has gained significant attention. Among these polysaccharides, chitosan (CS), a linear, mucoadhesive polymer, has shown promise in cancer treatment. This review summarizes current research on the potential applications of CS-based hydrogels as DDSs for CRC treatment, with a particular focus on smart hydrogels. These smart CS-based hydrogel systems are categorized into two main types: stimuli-responsive injectable hydrogels that undergo sol-gel transitions in situ, and single-, dual-, and multi-stimuli-responsive CS-based hydrogels capable of releasing drugs in response to various triggers. The review also discusses the structural characteristics of CS, the methods for preparing CS-based hydrogels, and recent scientific advances in smart CS-based hydrogels for CRC treatment.

We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis.

We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence.

The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons.

We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges.

In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation).

More randomised controlled trials are necessary.

This study is registered as PROSPERO CRD42019130504.

This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.

Mucinous adenocarcinoma of the appendix (MACA) follows a complex disease course with variable survival. Large-scale predictive modeling may determine subtle yet important prognostic factors otherwise unseen in smaller cohort analyses.

Patients with MACA were identified from the Surveillance, Epidemiology, and End Results (SEER) Research Plus database (2005-2019). Primary, secondary, and tertiary outcomes were disease-specific survival (DSS), overall survival (OS), and average annual percent change (AAPC) in incidence.

Among 4,258 included patients, MACA was most frequently diagnosed at 50 to 69 years (52.0%), with female preponderance (55.9%). MACA incidence AAPC was 3.8 (95% confidence interval [CI] 1.9-5.9). For patients with exclusive, first-diagnosis MACA included in survival analysis (3,222 patients), median DSS and OS were 118 and 88 months, respectively. In DSS-based multivariable analysis, worse prognosis was associated with non-Hispanic Black background (HR 1.36, 95% CI 1.02-1.82; p = 0.036), high grade (grade 3 HR 3.10, 95% CI 2.44-3.92; p < 0.001), lymphatic spread (HR 2.73, 95% CI 2.26-3.30; p < 0.001), and distant metastasis (HR 5.84, 95% CI 3.86-8.83; p < 0.001). In subcohort analysis of patients with rationale for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC, 2,387 patients), CRS-HIPEC was associated with survival benefit compared with surgery alone but only for moderate-grade tumors (median DSS/OS 138/138 vs. 116/87 months; p < 0.001).

Mucinous adenocarcinoma of the appendix incidence is increasing in the United States. Survival rates are affected by both demographics and classical risk factors, and CRS-HIPEC-associated survival benefit predominantly occurs in moderate-grade tumors. Further exploration of biologic and clinicopathologic features may enhance risk stratification for this disease.

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).

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.

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.

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 safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the clinicopathological features and to evaluate the safety and survival prognosis of CRS + HIPEC combined with urinary tract resection and reconstruction.

The patients who underwent urinary tract resection and reconstruction as part of CRS surgery were retrospectively selected from our disease-specific database for analysis. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were studied using a descriptive approach and the K-M analysis with log-rank comparison.

Forty-nine patients were enrolled. Perioperative serious AEs (SAEs) were observed in 11 patients (22.4%), with urinary SAEs occurring in 3 patients (6.1%). Additionally, there were 23 cases (46.8%) involving urinary adverse events (UAEs). The median overall survival (OS) in the entire cohort was 59.2 (95%CI: 42.1-76.4) months. The median OS of the UAE group and No-UAE group were 59.2 months (95%CI not reached), and 50.5 (95%CI: 11.5 to 89.6) months, respectively, with no significant difference (P = 0.475). Furthermore, there were no significant differences in OS based on the grade of UAEs or the number of UAEs (P = 0.562 and P = 0.622, respectively).

The combination of CRS + HIPEC with urinary tract resection and reconstruction is associated with a high incidence of Grade I-II UAEs, which do not have an impact on OS. The safety profile of this combined technique is acceptable. However, this is a retrospective single-center single-arm analysis, with limitations of generalizability and potential selection bias. The findings need high-level validation.

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major treatment of colorectal peritoneal carcinomatosis (CPC). The aim was to determine the disease-free survival (DFS) and overall survival (OS) of patients undergoing CRS-HIPEC for CPC and factors associated with long-term survival (LTS).

consecutive CPC patients who underwent CRS-HIPEC at a HIPEC center between 2007 and 2021 were included. Actual survival was calculated, and Cox proportional hazards models were used to identify factors associated with OS, DFS and LTS.

there were 125 patients with CPC who underwent primary CRS-HIPEC, with mean age of 54.5 years. Median follow-up was 31 months. Average intraoperative PCI was 11, and complete cytoreduction (CC-0) was achieved in 96.8%. Median OS was 41.6 months (6-196). The 2-year and 5-year OS were 68% and 24.8%, respectively, and the 2-year DFS was 28.8%. Factors associated with worse OS included pre-HIPEC systemic therapy, synchronous extraperitoneal metastasis, and PCI ≥ 20 (p < 0.05). Progression prior to CRS-HIPEC was associated with worse DFS (p < 0.05). Lower PCI, fewer complications, lower recurrence and longer DFS were associated with LTS (p < 0.05).

CRS and HIPEC improve OS in CPC patients but they have high disease recurrence. Outcomes depend on preoperative therapy response, extraperitoneal metastasis, and peritoneal disease burden.

A 44-year-old woman with Lynch syndrome was referred to our hospital for treatment of recurrence of microsatellite instability-high rectal cancer. [18F]Fluorodeoxyglucose (18FDG)-positron emission tomography revealed a peritoneal metastasis with invasion to the small intestine and left ureter. The peritoneal metastasis was diagnosed initially as unresectable because of extensive invasion to the left ureter requiring nephrectomy. Hence, first-line treatment with pembrolizumab was started. After the first course of pembrolizumab, she developed hydronephrosis and a resulting urinary tract infection (UTI). A percutaneous nephrostomy was performed to control the UTI. After six courses of pembrolizumab, 18FDG-positron emission tomography showed that the peritoneal metastasis was smaller with significantly reduced 18FDG uptake, and it was then diagnosed as resectable without nephrectomy. She underwent R0 resection of the peritoneal metastasis with partial resection of the small intestine. Intraoperatively, the peritoneal metastasis showed no invasion of the left ureter, allowing its preservation. The percutaneous nephrostomy was removed postoperatively, and she has not developed any subsequent UTIs. Histopathologically, the tumor showed a pathological complete response to pembrolizumab. To the best of our knowledge, this is the first case of conversion therapy with pembrolizumab for peritoneal metastasis with hydronephrosis.

Cytoreductive surgery with Hyperthermic Intraperitoneal Chemotherapy (CR-HIPEC) is a locorregional surgical therapy applied in patients with peritoneal-only metastatic disease of primary abdominal malignancies. Integrated in a multimodal treatment, CR-HIPEC is associated with increased overall survival. In cases of peritoneal-site only relapse, it may be carried out more than once.

Patients who received a CR-HIPEC between January 2016 and December 2020 at Instituto Português de Oncologia do Porto, Portugal were included in a unicentric, retrospective, observational study. Short- and long-term outcomes after surgery were analyzed.

In this period, 259 CR-HIPEC were performed on 248 patients. Of these, 31 were CR-HIPEC repeats, with 6 being the third HIPEC in the same patient. Of the 31 cases, 15 (48.4 %) had an appendicular origin. Mean PCI in re-HIPEC group was 10.6 (SD ± 7.1). No significant differences in baseline characteristics between the first and re-HIPEC groups were found, except for mean PCI, higher in the 1st HIPEC group (p = 0.047). In re-HIPEC group, major complications rate (CT-CAE 3-4) was 12.9 % (n = 4), without postoperative mortality. The 1st and re-HIPEC group had similar morbidity rates and hospitalization time. With a median follow-up time of 44 months, relapse rate after repeat CR-HIPEC was 45.2 % (n = 14), with a mean overall survival (OS) of 68.7 months and 5-year OS of 78 %.

Repeat CR-HIPEC is a safe approach with an acceptable complication rate for its complexity, associated with a survival benefit in selected patients. It should be presented as a valid therapeutic option in recurrent peritoneal disease.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with peritoneal carcinomatosis is promising but has potential for significant morbidity and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) is a standardized protocol designed to optimize perioperative care. This study describes trends in epidural and opioid use after implementing ERAS for CRS-HIPEC at a tertiary academic center.

A retrospective analysis of patients undergoing CRS-HIPEC from January 2020 to September 2023 was conducted. ERAS was implemented in February 2022. Medication and outcomes data were compared before and after ERAS initiation. All opioids were converted to morphine milligram equivalents (MMEs).

A total of 136 patients underwent CRS-HIPEC: 73 (54%) pre- and 63 (46%) post-ERAS. Epidural usage increased from 63% pre-ERAS to 87% post-ERAS (p = 0.001). Compared with those without epidurals, patients with epidurals had decreased total 7-day oral and intravenous (IV) opioid requirements (45 MME vs. 316 MME; p < 0.001). There was no difference in 7-day opioid totals between pre- and post-ERAS groups. After ERAS, more patients achieved early ambulation (83% vs. 53%; p < 0.001), early diet initiation (81% vs. 25%; p < 0.001), and early return of bowel function (86% vs. 67%; p = 0.012).

ERAS implementation for CRS-HIPEC was associated with increased epidural use, decreased oral and IV opioid use, and earlier bowel function return. Our study demonstrates that epidural analgesia provides adequate pain control while significantly decreasing oral and IV opioid use, which may promote gastrointestinal recovery postoperatively. These findings support the implementation of an ERAS protocol for effective pain management in patients undergoing CRS-HIPEC.

Despite thorough preoperative work-up for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), so called open-close (OC) procedures as a result of irresectable disease remain common. Currently, diagnostic laparoscopy (DLS) is considered the gold standard, and consequently overrules the results of computed tomography (CT) scans; however, certain regions of the abdomen are difficult to assess and postoperative adhesion formation may further compromise staging during DLS.

To determine whether better clinical assessment could be achieved by combining the results of DLS and preoperative CT scans during a multidisciplinary team (MDT) meeting.

All patients who were eligible for CRS-HIPEC after DLS, but eventually underwent an OC procedure between 2010 and 2018 were selected. Radiological reassessment of CT scans was performed and combined with assessment of the DLS during a MDT meeting. The MDT was blinded for the outcome of the procedure (OC vs. CRS-HIPEC).

The majority of the OC procedures (69%) was correctly predicted by the MDT. In most patients (88%), this conclusion was based on the combination of the radiological and surgical peritoneal cancer index (PCI). CT was particularly accurate for detection of larger tumor deposits in the abdominal regions, as 84%-86% was detected. Assessment of lesions in the small bowel regions is troublesome; 72% of lesions are missed on the preoperative CT scan.

A combination of radiological and surgical assessment of the PCI may lead to improved preoperative patient selection for CRS-HIPEC.

Hepatocellular carcinoma with peritoneal metastasis (HCC-PM) has a poor outlook. Traditional treatments have limited effect on survival. The safety and efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) have been shown in other peritoneal cancers. This study evaluates the role of CRS + HIPEC in HCC-PM.

A retrospective analysis of HCC-PM patients treated with CRS + HIPEC at Beijing Shijitan Hospital from March 2017 to December 2023 was conducted, assessing clinical features, severe adverse events (SAEs), and overall survival (OS) rates.

The study population comprised 10 HCC-PM patients who underwent CRS + HIPEC. The median peritoneal cancer index (PCI) was 25, and complete cytoreduction (CC0 ~ 1) was achieved in half of the patients. Three patients experienced SAEs within 30 days postoperatively. The 1-year, 3-year, and 5-year OS rates were recorded as 89.0%, 89.0%, and 21.0% respectively, with a median OS1 of 107.8 months and OS2 of 49.9 months. The median progression-free survival (PFS) was 5.0 months.

The application of CRS + HIPEC offers significant benefits to patients with HCC-PM. A selected group of patients may achieve prolonged PFS. Incorporating CRS + HIPEC into the treatment paradigm can thus be considered a strategic therapeutic option for patients with HCC-PM.

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.

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.

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).

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.

An incisional hernia (IH) after major abdominal surgery is an unwanted complication particularly following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC). The frequency of IH among patients treated with CRS and HIPEC remains unexpectedly high in various studies. This study aimed to analyze the incidence, determine the factors contributing to the occurrence of IH, and develop methods to reduce the incidence of IH.

We retrospectively analyzed data from a prospectively maintained structured computerized comprehensive database of 360 patients who had undergone CRS and HIPEC after January 2013 and completed two years of follow-up before December 2023. All patients were followed for a minimum period of two years with physical examination and radiological imaging when required and the occurrence of IH was documented. We used SPSS software version 24 to analyze the data using appropriate statistical tests. We set a significance threshold of p < 0.05.

Within two years of undergoing CRS and HIPEC, 25 patients (6.9%) out of 360 developed IH, indicating an annual incidence rate of 3.5%. The mean duration of hospitalization for the CRS/HIPEC procedure was 8.4 ± 4.13 days. Fifty-two (14.4%) patients experienced early post-operative surgical complications. The development of IH in our series was significantly associated with obesity (76% vs. 8.4%, P = 0.001), the occurrence of early post-operative surgical complications (48% vs. 12%, P = 0.001), mainly category III complications (44% vs. 7.1%), category IV complications (24% vs. 2.9%) according to Clavien-Dindo classification, post neoadjuvant chemotherapy status (72% vs. 87%, P = 0.045) and need for bowel anastomosis (32% vs. 11%, P = 0.002).

The lower incidence of IH following CRS and HIPEC in our patient cohort than in the literature can be attributed to a combination of factors, including the use of meticulous surgical techniques and the use of an abdominal binder postoperatively, particularly in obese patients.

Colorectal cancer (CRC) poses a significant global health challenge. Notably, the risk of CRC escalates with age, with the majority of cases occurring in those over the age of 65. Despite recent progress in tailoring treatments for early and advanced CRC, there is a lack of prospective data to guide the management of older patients, who are frequently underrepresented in clinical trials. This article reviews the contemporary landscape of managing older individuals with CRC, highlighting recent advancements and persisting challenges. The role of comprehensive geriatric assessment is explored. Opportunities for treatment escalation/de-escalation, with consideration of the older adult's fitness level. are reviewed in the neoadjuvant, surgical, adjuvant, and metastatic settings of colon and rectal cancers. Immunotherapy is shown to be an effective treatment option in older adults who have CRC with microsatellite instability. Promising new technologies such as circulating tumor DNA and recent phase III trials adding later-line systemic therapy options are discussed. Clinical recommendations based on the data available are summarized. We conclude that deliberate efforts to include older individuals in future colorectal cancer trials are essential to better guide the management of these patients in this rapidly evolving field.

Patients with colorectal peritoneal metastases (CRPM) are increasingly treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, data identifying preoperative risk factors for poor oncologic outcomes after this procedure are limited. We aimed to determine the prognostic value of preoperative CEA, CA 125, and CA 19-9 on disease progression after CRS/HIPEC.

Patients with CRPM treated with curative intent CRS/HIPEC from 12 participating sites in the United States from 2000 to 2017 were identified. Progression-free survival (PFS), defined as disease progression or recurrence, was the primary outcome.

In 279 patients who met inclusion criteria, the rate of disease progression was 63.8%, with a median PFS of 11 months (interquartile range [IQR] 5-20). Elevated CA 19-9 was associated with dismal PFS at 2 years (8.9% elevated vs. 30% not elevated, p < 0.01). In 113 patients who underwent upfront CRS/HIPEC, CA 19-9 emerged as the sole tumor marker independently predictive of worse PFS (hazard ratio [HR] 2.88, p = 0.048). In the subgroup of patients who had received neoadjuvant therapy (NAT), no variable was independently predictive of PFS. CA 19-9 levels over 37 U/ml were highly specific for accelerated disease progression after CRS/HIPEC. Lastly, there was no association between PFS and elevated CEA or CA 125.

Elevated CA 19-9 is associated with decreased PFS in patients with CRPM. While traditionally CEA is the main tumor marker assessed in colon cancer, we found that CA 19-9 may better inform preoperative risk stratification for poor oncologic outcomes in patients with CRPM. However, prospective studies are required to confirm this association.

Peritoneal surface malignancies (PSM) are commonly known to have a dismal prognosis. Over the past decades, novel techniques such as cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced for the treatment of PSM which could improve the overall survival and quality of life of patients with PSM. The decision to proceed with CRS and HIPEC is often challenging due the complexity of the disease, the extent of the procedure, associated side effects, and potential risks. Here, we present our experience with CRS and HIPEC to add to the ongoing discussion about eligibility criteria, technical approach, and expected outcomes and contribute to the evolution of this powerful and promising tool in the multidisciplinary treatment of patients with primary and secondary PSM.

A single-center retrospective chart review was conducted and included a total of 40 patients treated with CRS and HIPEC from April 2020 to September 2022 at the University Hospital Münster Department of Surgery. All patients had histologically confirmed primary or secondary peritoneal malignancies of various primary origins.

Our study included 22 patients with peritoneal metastases from gastric cancer (55%), 8 with pseudomyxoma peritonei (20%), 4 with mesothelioma of the peritoneum (10%), and 6 patients with PSM originating from other primary tumor locations. Median PCI at time of cytoreduction was 4 (0-25). Completeness of cytoreduction score was 0 in 37 patients (92.5%), 1 in two patients (5%), and 2 in one patient (2.5%). Median overall survival across all patients was 3.69 years.

Complete cytoreduction during CRS and HIPEC can be achieved for patients with low PCI, for patients with high PCI in low-grade malignancies, and even for patients with initially high PCI in high-grade malignancies following a significant reduction of cancer burden due to extensive preoperative treatment with PIPAC and systemic chemotherapy.

Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends are understudied for colorectal peritoneal metastases (CRPM).

We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC.

A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months, p = 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14, p < 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively, p < 0.001).

Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels.

Venous thromboembolism and postoperative bleeding are complications of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this systematic review was to summarize current knowledge on the effect of cytoreductive surgery with HIPEC on coagulation and fibrinolysis within 10 days after surgery. Studies were identified in PubMed, Embase, and Web of Science on December 12, 2022. Data on biomarkers of coagulation and fibrinolysis measured preoperatively up to the 10th postoperative day were extracted. Among 15 included studies, 13 studies reported markers of primary hemostasis. Eleven studies found reduced platelet count following cytoreductive surgery with HIPEC and two studies reported reduced platelet function. Twelve studies reported impaired secondary hemostasis until postoperative day 10 indicated by prolonged international normalized ratio, prothrombin time, and activated partial thromboplastin time. Fibrinogen was decreased in three studies from preoperative to postoperative day 3 switching to increased levels until postoperative day 10. In accordance, three studies found reduced maximum amplitude and maximum clot firmness by thromboelastography/thromboelastometry (ROTEM/TEG) on the first postoperative day indicating impaired clot strength. Four studies demonstrated increased d-dimer, factor (F) VIII, and thrombin generation during the 10 postoperative days. Four studies investigated fibrinolysis by ROTEM/TEG and plasminogen activator inhibitor-1 (PAI-1) after cytoreductive surgery with HIPEC reporting contradictive results. In conclusion, a decrease in platelet count and subtle changes in secondary hemostasis were found following cytoreductive surgery with HIPEC. Data on the effect of cytoreductive surgery with HIPEC on fibrinolysis are sparse and this needs to be further investigated.

Peritoneal metastases from colon cancer are a particularly challenging disease process given the limited response to systemic chemotherapy. In patients with isolated peritoneal metastases, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy offers a potential treatment option to these patients with limited peritoneal metastases as long as a complete cytoreduction is achieved. Decision about a patient's candidacy for this treatment modality should be undertaken by a multidisciplinary group at expert centers.

Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) improves survival compared with chemotherapy alone in patients with peritoneal carcinomatosis (PC) of colorectal (CRC) origin, however, long-term survival data are lacking. We report the actual survival of patients who underwent CRS/HIPEC for PC of CRC origin with a minimum potential 5-year follow-up period to identify factors that preclude long-term survival.

We performed a retrospective analysis of a prospective database, analyzing patients undergoing CRS/HIPEC for PC of CRC origin from 2007 to 2017. Patients with aborted CRS/HIPEC, postoperative follow-up <90 days, or non-CRC histology were excluded. Overall survival (OS) and disease-free survival (DFS) were measured from date of surgery. Surviving patients with <60 months of follow-up were censored at date of last follow-up.

A total of 103 patients met inclusion criteria and were analyzed. CC score 0-1 was achieved in 89.3% of patients, and median peritoneal cancer index (PCI) was 9 (interquartile range [IQR] 5-17). Ninety-day mortality was 2.9%. The median follow-up of survivors was 88 months. Five-year OS was 36%, and median OS was 42.5 months. Factors independently associated with poor survival included high PCI (PCI = 14-20, hazard ratio [HR] 3.1, p = 0.007, and PCI > 20, HR 5.3, p ≤ 0.001) and incomplete CRS (CC score-2, HR 2.96, p = 0.02). Patients with low PCI (0-6) had 5-year OS 60.7%.

Actual 5-year OS was 36% and median OS was 42.5 months. Our study demonstrates that patients with PC from CRC origin with low PCI who undergo complete surgical resection can achieve favorable long-term survival.

Some studies show that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) may improve overall survival and is a possible curative treatment for selected colorectal cancer (CRC) patients with restricted peritoneal metastasis (PM). The value of HIPEC in preventing PM of CRC is still controversial.

In this retrospective propensity score matching (PSM) cohort study, all patients with cT4N0-2M0 undergoing treatment at a single institution in China (2014-2018) were reviewed. The 3-year disease-free survival (DFS) was set as the primary outcome, and the 3-year PM rate was also analyzed.

220 patients were included in this study for analysis. After 1:3 PSM: HIPEC (n = 45) and No HIPEC (n = 135). Through analysis, it was found that prophylactic HIPEC correlated to better DFS [hazard ratio (HR) 0.43, 95 % confidence interval (CI) 0.19-0.95; p = 0.037], and N2 stage correlated to worse DFS [HR 1.97, 95 % CI 1.09-3.56; p = 0.025]. For laparoscopic surgery subgroup analyses, 3-year PM rate of patients with laparoscopic surgery was 13.8 % in No HIPEC group, and 2.6 % in HIPEC group (p = 0.070). Besides, no post-operative death occurred, the anastomotic leakage rate was 2.2 % in HIPEC group and 0.7 % in the control group (p = 0.439).

Prophylactic HIPEC may improve the prognosis in patients with cT4N0-1M0 CRC, but not in cT4N2M0 CRC, and it does not significantly increase surgery-related complications. Laparoscopic surgery followed by HIPEC for T4 stage CRC may not increase risk of PM.

The underlying mechanism of colorectal cells developing into cancer cells has been extensively investigated, yet is still not fully delineated, resulting in the treatment of advanced colorectal cancer (CRC) remains regrettably an unmet need. Zinc Finger Protein 746/Parkin-interacting substrate (ZNF746/PARIS) has previously been identified to play a fundamental role on bladder cancer cell proliferation and metastasis that were effectively inhibited by melatonin (Mel). In this study, we utilized ex vivo/in vivo studies to verify whether the ZNF746 signaling was also crucial in CRC growth/invasion/migration. Tissue-bank specimens showed that the protein expression of ZNF746 was significantly increased in CRC than that of healthy colorectal tissues (p < 0.001). Additionally, in vitro study demonstrated that excessive expression of ZNF746 significantly inhibited mitochondrial activity via (1) interfering with the dynamic balance of mitochondrial fusion/fission and (2) inhibiting the protein expression of MFN1/MFN2/PGC1a (all p < 0.001). Furthermore, we identified that inhibition of ZNF746 protein expression significantly reduced the resistance of CRC cell lines to the anticancer drug of 5-FU (p < 0.001), whereas overexpression of ZNF746 significantly augmented resistance of CRC cells to 5-FU (all p < 0.001). Finally, using the cell culture method, we found that combined Mel and 5-FU was superior to merely one on promoting the CRC cell apoptosis (p < 0.001). Our results confirmed that ZNF746 signaling played a cardinal role of CRC cell proliferation/survival and combined Mel and 5-FU treatment attenuated the resistance of CRC cells to the drug mainly through suppressing this signaling.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the 5-year survival for colorectal cancer (CRC) patients with peritoneal metastases (PM). Little is known about recurrence patterns and recurrence rates between synchronous (S) and metachronous (M) PM following CRS+HIPEC. We aimed to describe the recurrence patterns, overall survival (OS) and disease-free survival (DFS) in S-PM and M-PM patients after complete CRS+HIPEC. From June 2006 to December 2020, a prospective cohort study included 310 CRC patients, where 181 patients had S-PM (58.4%) and 129 patients had M-PM (41.6%). After a median 10.3-month follow-up, 247/310 (79.7%) patients experienced recurrence, and recurrence sites included isolated peritoneal (32.4%), multifocal (peritoneal and liver and/or lung(s)) (22.7%), isolated liver (17.8%), isolated lung (10.5%) and other (16.6%) sites. Recurrence patterns did not differ between S-PM and M-PM. M-PM patients had an impaired DFS compared to S-PM patients (9.4 months (95% CI: 7.3-12.1) vs. 12.5 months (95% CI: 11.2-13.9), p = 0.01). The median OS was similar for S-PM and M-PM (38.4 months (95% CI: 31.2-46.8) vs. 40.8 months (95% CI: 28.8-46.8), p = 0.86). Despite frequent recurrence at extraperitoneal locations, long-term survival was achievable after CRS+HIPEC in CRC patients with PM. The recurrence patterns and OS did not differ between groups, yet M-PM patients had a shorter DFS.