Standard treatment for resectable peritoneal metastasis (PM) includes the combination of cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Postoperative evisceration is a rare but major complication after CRS and HIPEC. This study aimed to identify the risk factors associated with evisceration after HIPEC, comparing outcomes between open and closed abdominal HIPEC.

We conducted a retrospective multi-center study analyzing data of 233 patients with PM who underwent CRS/HIPEC between 2014 and 2023. Patients were categorized based on the HIPEC technique: Open (OPEN_HIPEC), n = 110; Closed abdominal technique (CLOSED_HIPEC), n = 123). We aimed to identify patient factors associated with evisceration within 30 days of CRS/HIPEC, using multivariate analysis.

Among 233 patients included, 129 (55.4 %) were women. The median age was 60 [51; 67] years. The OPEN_HIPEC group was significantly younger than the CLOSED_HIPEC group (median 57 [47; 62] vs 63 [54; 70] years; p ≤ 0.001) with a higher PCI score (median 9.5 [5; 17] vs 6 [2; 11]; p ≤ 0.001). Severe complications were similar between OPEN and CLOSED_HIPEC: 17 (15.5 %) vs 15 (12.2 %); p = 0.471 with no mortality. Eight (3.4 %) patients had postoperative evisceration with significantly more occurrences in the OPEN_HIPEC than in the CLOSED_HIPEC group (7/110 (6.4 %) vs 1/123 (0.8 %); p = 0.028). Univariate analysis identified chronic obstructive pulmonary disease (COPD)/respiratory pathology (HR = 7.02 [1.76-28.1]) and PCI score category of 11-15 (HR = 5.09 [1.03-25.2] as risk factors. Multivariate analysis identified a history of COPD/respiratory pathology (HR = 7.39 [1.85-29.6], p = 0.005) and OPEN_HIPEC (HR = 8.37 [1.03-68.1], p = 0.047) as risk factors of postoperative evisceration. Although suture material was not identified as a significant factor by the analysis, all eviscerations in the OPEN_HIPEC group were observed following musculoaponeurotic closures using Vicryl 1 sutures.

Following CRS/HIPEC treatment, 3.4 % patients had evisceration by day 30. A history of COPD/respiratory pathology and OPEN_HIPEC technique were identified as independent risk factors associated with evisceration, necessitating reintervention. It should also be noted that in the OPEN_HIPEC group there were no eviscerations after the change to PDS sutures.

In gastric cancer, the only opportunity for a cure is with surgical resection. Fluorescence-guided surgery is an emerging field that has the potential to improve rates of R0 resections. Mouse models with patterns of disease spread that would be deemed operable in patients are required for the testing of potential fluorescence-guided surgery probes.

One million cells of the human gastric cancer cell line MKN45 were suspended in 50 μL of phosphate-buffered saline and Matrigel and injected into the mouse stomach with a 29-gauge needle. After 8 to 12 weeks of tumor growth, mice were killed and laparotomy was performed to determine rates of tumor engraftment, local or distant spread, and involvement of celiac lymph nodes. For tumor labeling, mice were randomized to receive intravenous injection of an anti-CEA antibody (M5A), or IgG as a control, conjugated with the near-infrared dye IRDye800CW. Fluorescence imaging was performed using the LI-COR Pearl Imaging System 72 hours later.

Infiltrative tumors were identified in 76.5% (n = 34) of mice. Intra-abdominal or peritoneal metastases were seen in 23.5% and carcinomatosis was seen in 5.9% of mice. Celiac lymph node metastases were seen in 55.5% of mice. M5A-IR800 administration resulted in bright labeling of primary tumors and metastatic celiac lymph nodes. Hematoxylin and eosin staining demonstrated incorporation of the gastric cancer cells throughout the layers of the mouse stomach and the presence of metastatic gastric cancer cells in celiac lymph nodes.

This new locoregional mouse model can be used to validate additional agents for their use in fluorescence guided surgical resection of gastric cancer.

Gastric cancer (GC) commonly presents in advanced stages with metastatic spread to the peritoneal cavity, and outcomes associated with gastric cancer with peritoneal metastasis (GCPM) continue to carry a dismal prognosis. Persistent challenges in the detection of peritoneal metastasis (PM) have resulted in a relative paucity of high-quality data to inform management decisions. Several consensus groups have published recommendations to guide management, including most recently the National Comprehensive Cancer Network guidelines, which now include cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a potential treatment modality in select patients with GCPM. Multiple clinical trials have investigated the use of CRS/HIPEC and other peritoneal-directed therapies, such as intraperitoneal chemotherapy (IPC) and pressurized intraperitoneal aerosolized chemotherapy (PIPAC). As high-volume centers work to incorporate such therapies into their practice, ongoing clinical trials are aimed at understanding their efficacy. Recent findings have improved understanding of the mechanisms and pathophysiology underlying GCPM while the discovery of novel targets offers potential for drug development and therapeutic strategies to overcome treatment resistance. This review highlights recent advancements and addresses the persistent challenges in managing GCPM while also offering a comprehensive summary of current guidelines and treatment strategies.

Peritoneal metastasis in gastric cancer is associated with a very poor prognosis with a median overall survival of seven to 15 months if treated with systemic chemotherapy only. Studies have shown improved survival with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in selected group of patients, when compared to systemic chemotherapy alone. In spite of promising results, this is not the standard of care till date. The aim of our study was to evaluate the long-term outcome for the patients of gastric cancer with peritoneal metastases undergoing cytoreductive surgery and HIPEC at our institute.

Retrospective analysis of prospectively maintained data of all patients, who underwent cytoreductive surgery and HIPEC during the period of 2015-2023, was performed. All relevant pre-operative, peri-operative, post-operative and histopathological data was analyzed and overall survival and disease-free survival calculated.

Twenty-three patients of gastric cancer with peritoneal metastasis (PCI < / = 7) underwent cytoreductive surgery and HIPEC during the study period. At a median follow-up of 12 months, median disease-free survival (DFS) and overall survival (OS) were 12 months and 35 months, respectively. One-year and three-year DFS were 48.5% and 23%, respectively. One-year and three-year OS was 85% and 45.4%, respectively.

Cytoreductive surgery and HIPEC can be considered to be safe and effective treatment strategy in a select group of gastric cancer patients with peritoneal metastasis leading to a meaningful survival as compared to palliative systemic chemotherapy.

To investigate the prognostic value of the apparent diffusion coefficient (ADC) calculated from diffusion-weighted imaging (DWI) to cytoreductive surgery (CRS), with or without hyperthermic intraperitoneal chemotherapy (HIPEC), for gastric cancer (GC) patients with peritoneal metastasis (PM).

Between May 2016 and December 2020, 95 newly diagnosed GC patients with PM who underwent CRS combined with HIPEC (CRS + HIPEC group, n = 61) and CRS alone (CRS group, n = 34) were retrospectively included. All patients underwent abdominal 3.0 T MRI scan, including DWI, and the mean ADC (ADCmean), minimum ADC (ADCmin), and maximum ADC (ADCmax) values of the whole-volume tumor were measured. The prognostic value of the ADC parameters and clinical and histopathological characteristics were investigated by univariate and multivariate Cox analyses.

The median overall survival (OS) periods of the CRS + HIPEC and CRS groups were 18 and 9 months, respectively ([hazard ratio (HR) = 0.44 [95% CI: 0.27-0.71], P<0.001). The ADCmean and ADCmin values were positively correlated with OS in all patients (Spearman's rho [R] = 0.361 and 0.470), as well as in the CRS + HIPEC (R = 0.369 and 0.417) and CRS (R = 0.192 and 0.409) groups. The multivariate Cox analysis demonstrated that the ADCmean ≤ 1.39 × 10- 3 mm2/s and ADCmin ≤ 0.77 × 10- 3 mm2/s were significantly associated with a negative prognosis in the total population (HR = 1.68 [95% CI: 1.02-2.75] and 2.48 [95% CI: 1.51-4.08], P all < 0.05) and the CRS + HIPEC group (HR = 2.22 [95% CI: 1.19-4.14] and 2.37 [95% CI: 1.26-4.37], P all < 0.05), along with pathologic T and N stages. Only the ADCmin ≤ 0.77 × 10- 3 mm2/s was identified as an independent prognostic factor in the CRS group (HR = 3.49 [95% CI: 1.19-10.20], P = 0.022).

The minimum ADC was identified as a strong independent prognostic factor for GC patients with PM who underwent CRS, with or without HIPEC.

Despite advances in systemic therapy, metastatic gastric cancer is associated with a poor prognosis. As peritoneal disease is common, several studies looked at the potential benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) in this context, with encouraging results. However, no Canadian data currently exists on the subject.

This study aims to report characteristics and outcomes of Canadian patients who underwent cytoreductive surgery and HIPEC (CRS-HIPEC) for gastric cancer associated with peritoneal disease or positive peritoneal cytology. This multicenter retrospective study included patients 18 years or older with gastric cancer associated with isolated peritoneal involvement who underwent CRS-HIPEC in five tertiary centers from 2016 to 2022.

CRS-HIPEC was performed on 20 patients aged 34-69 years old, most of whom presented with poorly differentiated (90 %) adenocarcinoma, with synchronous peritoneal disease (95 %). Median PCI was 3 (0-13). The associated 90-day morbidity rate, defined as Clavien-Dindo grade III and above complications, was 10 %. At a mean follow-up of 23.3 months (range 4-48), 25 % of patients remained disease-free, with an estimated median overall survival of 24.2 months.

CRS-HIPEC for gastric cancer can achieve longer term survival in highly selected patients with low-burden peritoneal disease or positive cytology. Ongoing randomized trials will further clarify patients' selection criteria and benefits of this approach.

The third version of the national S3 guideline for gastric cancer is currently being finalised and will be published in the near future. Therefore, this review article primarily discusses the aspects of the current 2019 version and provides an outlook on the innovations in the upcoming version. Emphasis will be placed on the transfer of care to centres with appropriate expertise. Overall, previous revisions of the guideline have placed an increased focus on the genetic aspects of the disease and have specified corresponding risk groups for the occurrence of this neoplasia (including the presence of a CDH1 mutation or HNPCC carriers). In addition, more "borderline" cases for surgery, such as patients with oligometastasis or peritoneal carcinomatosis, have been included in the guidelines. However, for the time being, these patient groups should only be treated in trials. Finally, the guideline discusses the increasing use of immunotherapy in current and future treatment regimens, in addition to the current chemotherapeutic standard of care analogous to the FLOT regimen. New targeted therapeutic approaches such as monoclonal antibodies against claudin 18.2 will complement the treatment of gastric cancer and will certainly be included in the next version of the guideline.

Gastric cancer with peritoneal metastases (GC-PM) carries a poor prognosis and estimated survival is less than 6 to 12 months. One potential treatment of GC-PM is cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Success of this treatment largely relies on tumor biology and patient selection. These operations carry a high risk of morbidity and mortality and their efficacy in GC-PM remains controversial. This study will review the updated literature for CRS ± HIPEC in patients with GC-PM.

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.

The peritoneum is a common metastatic site in gastric cancer. The prognosis of synchronous peritoneal metastases compared to other metastatic sites in gastric cancer remains understudied. This study aims to evaluate the impact of peritoneal metastases on survival in patients with metastatic gastric cancer.

Patients with gastric cancer and synchronous metastases between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Patients were categorized based on the site of metastases. Median overall survival (OS) was calculated for each metastatic site group. Multivariable Cox regression analyses were performed to evaluate the association between patient, tumour, and treatment characteristics, including the impact of systemic therapy, on OS.

A total of 4072 patients were included, of whom 1835 (45.1%) had peritoneal metastases. Of these, 58.1% had isolated peritoneal metastases. For patients with metastatic gastric cancer treated with systemic therapy, the median OS was 9.0 months (95% confidence interval (CI): 8.6-9.5), compared to 1.7 months (95% CI: 1.7-1.9) for treatment-naïve patients, who received only palliative care. The survival for patients with isolated peritoneal metastases (4.4 months, 95% CI: 4.0-4.8 months) was similar to those with isolated non-peritoneal metastases (4.6 months, 95% CI: 4.2-5.1 months, adjusted HR: 0.94, 95% CI: 0.86-1.03, p = 0.185). Systemic therapy was associated with comparable survival in patients with peritoneal metastases and those with metastases at other sites.

This study demonstrates that there is no statistically significant difference in survival between patients with isolated peritoneal metastases and those with isolated non-peritoneal metastases in gastric cancer. Our findings emphasize the unique prognostic landscape for peritoneal metastases in gastric cancer, underscoring the need for disease-specific evaluations, rather than relying on assumptions derived from other cancer types.

None.

Acute kidney injury after CRS + HIPEC is a serious postoperative complication, but only a few studies have reported its postoperative risk factors. In addition, there are large discrepancies in the results of available observational studies.

We searched The Cochrane Library, Embase, Web of Science,and PubMed to identify observational studies reporting risk factors for AKI after CRS + HIPEC. A meta-analysis was performed to investigate the effect of various preoperative and intraoperative risk factors on AKI after CRS + HIPEC.

A total of 7 studies were included in this study, comprising 1550 patients who developed AKI after CRS + HIPEC. The results of meta-analysis showed that the significant preoperative risk factors were age, sex, BMI, eGFR, Hb, PCI, diabetes mellitus, and hypertension. IO cisplatin, IO SBP < 100 was identified as an intraoperative risk factor, whereas IO mitomycin emerged as a protective factor for postoperative AKI. In addition, the risk of postoperative AKI varied by primary tumor site, with Appendix being less prone to AKI, while mesothelioma and ovarian, two sites with a greatly elevated risk of postoperative AKI.

This meta-analysis identified a number of risk factors for postoperative AKI after CRS + HIPEC. By identifying these risk factors, it is more beneficial for clinicians to perform early preoperative interventions and select the most appropriate treatment strategy for their patients, thus minimizing the risk of postoperative AKI.

PROSPERO CRD42024585269.

Patients with gastric cancer peritoneal metastases (GCPM) have Stage IV disease. Systemic therapy is a crucial aspect of their care. Patients with GCPM should have their tumors tested for HER2 and PD-L1 expression and microsatellite instability for potential targeted therapies. If patients with synchronous GCPM have stable disease following neoadjuvant therapy, surgical intervention can be considered. Patients with positive cytology or low-volume peritoneal disease (peritoneal carcinomatosis index [PCI] < 7) may "convert" to negative cytology or resolution of peritoneal metastases following intraperitoneal therapy and may be candidates for subsequent gastrectomy.

This study aims to evaluate the effectiveness and safety of prophylactic hyperthermic intraperitoneal chemotherapy (P-HIPEC) in patients with locally advanced gastric cancer (AGC) after laparoscopic radical gastrectomy. Additionally, it explores how the frequency and timing of P-HIPEC influence treatment outcomes.

A retrospective analysis was conducted on 227 patients with locally AGC who underwent laparoscopic surgery at Maoming People's Hospital from January 2016 to December 2022. Patients were stratified into the HIPEC group (n=101) and the non-HIPEC group (n=126), based on whether they received postoperative P-HIPEC. Propensity score matching (PSM) was used to adjust for baseline characteristics, facilitating a comparative analysis of survival outcomes, postoperative complications and recurrence patterns. Cox regression analysis was performed to identify prognostic factors. Furthermore, the impact of varying P-HIPEC frequencies and initiation timings was evaluated.

No significant differences in overall survival (OS) or postoperative complication rates were observed between the two groups in the original and PSM cohorts. But the disease-free survival (DFS) of the HIPEC group was significantly higher than that of the non-HIPEC group (HR 0.569; 95% CI 0.362-0.894; p = 0.013) in the PSM cohort, with 1-year, 3-year, and 5-year DFS rates showing notable improvement (77.9% vs. 69.7%, 60.1% vs. 43.0%, and 46.2% vs. 25.5%). The incidence of isolated peritoneal metastasis (PM) was significantly lower in the HIPEC group (5.3% vs. 17.3%, p = 0.039). Multivariate Cox regression analysis identified P-HIPEC as an independent protective factor for DFS. Further analysis indicated that neither the number of P-HIPEC sessions had a significant impact on OS (p = 0.388) or DFS (p = 0.735), nor did the timing of P-HIPEC initiation affect OS (p = 0.620) or DFS (p = 0.488). Likewise, different P-HIPEC frequencies or initiation timings had no significant impact on postoperative complication rates or recurrence patterns.

P-HIPEC effectively reduces the risk of postoperative PM and improves DFS in patients with locally AGC without increasing postoperative complications. However, it does not significantly impact OS. Additionally, variations in the frequency and timing of P-HIPEC initiation do not significantly affect survival outcomes, postoperative complications, or recurrence patterns.

Gastric cancer is a significant global contributor to cancer-related mortality. Stage IV gastric cancer represents a significant percentage of patients in Western countries, with peritoneal dissemination being the most prevalent site. Peritoneal disease comprises two distinct entities, macroscopic (P1) and microscopic (P0CY1), which are associated with poor long-term survival rates. Although the present standard of treatment is palliative chemotherapy, a global controversy has arisen concerning specific patients with limited disease burden or conversion to negative lavage cytology following chemotherapy. Available approaches include systemic or intraperitoneal chemotherapy, upfront gastrectomy, and conversion surgery. This review consolidated the current evidence regarding multimodal management, indicating prolonged survival for this distinct subgroup of patients. Considering the complexity of peritoneal metastases, the potential of the multimodal approach unveils promising prospects for identifying the optimal treatment for this particular subset of stage IV patients and thus enhancing their survival outcomes.

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.

Standard treatment for resectable peritoneal metastases (PM) combines cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC); however, the rate of recurrence remains high and repeat CRS/HIPEC may be considered in well-selected patients. We describe our postoperative and oncological outcomes.

Between 1994 and 2024, data from 132 repeat CRS/HIPEC procedures were analyzed in this retrospective multicenter study. Morbimortality, overall survival (OS) and recurrence-free survival (RFS) were evaluated for colorectal peritoneal metastases (CRPM) and peritoneal pseudomyxoma (PMP).

Overall, 63 patients, including 55 patients with CRPM (87.3%) and 8 patients with PMP (12.7%), underwent CRS/HIPEC. Of these patients, 58 (92%) underwent CRS/HIPEC twice, 4 (6.3%) underwent CRS/HIPEC three times, and 1 (1.6%) underwent CRS/HIPEC four times. Peritoneal Carcinomatosis Index (PCI) score, operating room occupancy, complication and readmission rates at day 90, and length of intensive care unit and hospital stay were similar between the initial and first repeat CRS/HIPEC procedures. No 90-day postoperative mortality occurred. For CRPM, the median OS was 82.3, 53.9, and 74.5 months from the initial, first, and second repeat CRS/HIPEC procedures, respectively, with a median RFS of 22.0, 36.9, and 13.2 months, respectively. For PMP, after a median follow-up of 70.8 and 39.3 months from the initial and first repeat CRS/HIPEC procedures, respectively, all patients were alive, with a median RFS of 22.4 and 39.4 months, respectively. Multivariate analysis shown that no factor was significantly related to severe complications (Dindo-Clavien 3-4) or OS.

In selected patients with CRPM and PMP, CRS/HIPEC shows comparable results between the initial and repeat procedures in terms of postoperative outcomes, and appears to improve survival, especially for PMP. Repeat CRS/HIPEC is an option to be considered in patients presenting with CRPM or PMP.

Despite therapeutic treatments and the growing utilization of multimodal therapies, gastric cancer (GC) remains a highly aggressive malignancy with high mortality worldwide. Much of the complexity in treating GC is due to the high incidence of peritoneal metastasis (PM), with mean overall survival typically ranging from 4 to 10 months. With current systemic therapy, targeted therapies, and immunotherapies continuing to remain ineffective for GC/PM, there has been a significant growing interest in intraperitoneal (IP) therapies for the treatment of GC/PM. In this review, we summarize the development of PM and evolving treatment strategies for GC/PM. Furthermore, we explore the various advancements and outcomes of IP therapies, including heated intraperitoneal chemotherapy (HIPEC), neoadjuvant HIPEC, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC).

This study aimed to assess the impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) on the survival outcomes for patients with gastric cancer and peritoneal carcinomatosis (PC).

A retrospective analysis of the National Cancer Database from 2004 to 2020 identified patients with topography and histology codes consistent with gastric adenocarcinoma who underwent CRS/HIPEC. The exclusion criteria ruled out known other distant metastasis and missing key data. The study compared the CRS/HIPEC group with patients who had stage IV disease (with the same exclusions for distant metastases) and received systemic chemotherapy but no surgery to the primary site.

The study included 148 patients who underwent CRS/HIPEC. Their median age was 57 years (interquartile range [IQR], 47-66 years), with 57.4% of the patients identifying as male and 73.6% identifying as white. Most of the CRS/HIPEC patients had locally advanced disease, with 33.8% having pT4 disease and 23% patients having pN3 status. The Charlson-Deyo scores were 0 for 77% and 1 for 16.9% of the patients. The overall survival (OS) among the stage IV patients managed with CRS/HIPEC was significantly longer than for the patients receiving only systemic chemotherapy (median survival, 18.1 vs 9.3 months; p < 0.001), and the 1-year OS was 72.6% versus 38.8% (p < 0.05)). Among the stage IV patients, CRS/HIPEC showed better survival than systemic chemotherapy (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.44-0.73; p < .001) when control was used for the Charlson Deyo score, histology, age, and sex.

These results suggest the association of CRS/HIPEC with improved survival for selected patients with gastric adenocarcinoma and peritoneal disease. Some of this difference may have been due to selection bias, but the differences in the survival curves are robust.

The main aim of this review is to analyze postoperative complications after cytoreductive surgery and intraperitoneal chemotherapy. Although the literature in this field is ever growing, reporting on complication is not a given. Nevertheless, some main risk factors such as prior surgery, high tumor burden and the center's expertize have an impact on patient outcomes. Transparency is key, if we want to continue to improve.

Gastrointestinal tumors are the main causes of death among the patients. These tumors are mainly diagnosed in the advanced stages and their response to therapy is unfavorable. In spite of the development of conventional therapeutics including surgery, chemotherapy, radiotherapy and immunotherapy, the treatment of these tumors is still challenging. As a result, the new therapeutics based on (nano)biotechnology have been introduced. Hydrogels are polymeric 3D networks capable of absorbing water to swell with favorable biocompatibility. In spite of application of hydrogels in the treatment of different human diseases, their wide application in cancer therapy has been improved because of their potential in drug and gene delivery, boosting chemotherapy and immunotherapy as well as development of vaccines. The current review focuses on the role of hydrogels in the treatment of gastrointestinal tumors. Hydrogels provide delivery of drugs (both natural or synthetic compounds and their co-delivery) along with gene delivery. Along with delivery, hydrogels stimulate phototherapy (photothermal and photodynamic therapy) in the suppression of these tumors. Besides, the ability of hydrogels for the induction of immune-related cells such as dendritic cells can boost cancer immunotherapy. For more specific cancer therapy, the stimuli-responsive types of hydrogels including thermo- and pH-sensitive hydrogels along with their self-healing ability have improved the site specific drug delivery. Moreover, hydrogels are promising for diagnosis, circulating tumor cell isolation and detection of biomarkers in the gastrointestinal tumors, highlighting their importance in clinic. Hence, hydrogels are diagnostic and therapeutic tools for the gastrointestimal tumors.

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is one of the most effective treatments for intraperitoneal malignancies. However, current research on risk factors for postoperative complications needs to be more consistent. This study aimed to conduct a meta-analysis of the risk factors for postoperative complications in CRS + HIPEC patients.

Studies meeting the inclusion criteria were screened by searching the Embase, PubMed, Cochrane and Web of Science databases. RevMan and STATA software were used to analyze the data extracted from the included articles.

A total of 15 articles with 4021 patients were included in the meta-analysis. The results revealed that sex, elevated peritoneal cancer index, prolonged duration of surgery and smoking habits were risk factors for postoperative complications in CRS + HIPEC patients. In contrast, BMI, eGFR, age, history of preoperative chemotherapy, history of preoperative surgery, and history of neoadjuvant therapy had no significant effect on postoperative complications in the CRS + HIPEC group. The effects of diabetes, hypertension, preoperative albumin level, tumor location and chemotherapy regimen on the occurrence of complications need to be further investigated.

We identified several risk factors for postoperative complications after CRS + HIPEC, which should help clinicians minimize the incidence of postoperative complications and make more beneficial decisions for cancer patients who need treatment.

Peritoneal carcinomatosis carries a grim survival prognosis with complications ranging from the physical to the psychological. Cytoreductive surgery and infusion of heated intraperitoneal chemotherapy have evolved to become a commonly used treatment option in the multi-modal management of peritoneal carcinomatosis. Here, we examine the origins of surgery over a century ago as a potential cure for peritoneal carcinomatosis and how it has evolved with our knowledge of the disease to its present state. The origin of chemotherapy is similarly described as well as its progressive application in regional therapy, guided by the ongoing development of new agents, better understanding of peritoneal physiology, and improved systemic treatment. We show how these modalities began to be used in tandem, and standardized, leading to randomized trials and better understanding of the possibilities and limitations of treatment. Finally, we discuss the current status of patient selection for cytoreduction and future directions of intraperitoneal chemotherapy.

Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416).

Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m2 every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures.

In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased.

The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments.

Despite advances in systemic chemotherapy, patients with gastric cancer (GC) and peritoneal metastases (PMs) continue to have poor prognoses. Intraperitoneal (IP) administration of Paclitaxel (PTX) combined with systemic chemotherapy shows promise in treating PMs from GC. However, methods of drug administration need to be optimized to maximize efficacy. In this study, we utilized a mouse model with PMs derived from a human GC cell line, administering PTX either IP or intravenously (IV), and Carboplatin (CBDCA) IV 0, 1, and 4 days after PTX administration. The PMs were resected 30 min later, and concentrations of PTX and CBDCA in resected tumors were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results indicated that PTX concentrations were higher with IP administration than with IV administration, with significant differences observed on days 0 and 1. CBDCA concentrations 4 days post-IP PTX administration were higher than with simultaneous IV PTX administration. These findings suggest that IP PTX administration enhances CBDCA concentration in peritoneal tumors. Therefore, sequential IV administration of anti-cancer drugs appears more effective than simultaneous administration with IP PTX, a strategy that may improve prognoses for patients with PMs.

In gastric cancer, peritoneal metastasis is the most common form of metastasis and leads to dismal prognosis. We aimed to evaluate the safety and efficacy of combining perioperative intraperitoneal (IP) plus systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with limited peritoneal metastasis or even after reducing peritoneal tumor burden by upfront IP chemotherapy.

Patients were enrolled in phase Ib in a 3 + 3 dose escalation of IP paclitaxel plus a fixed dose of IP cisplatin and oral S-1. In phase II, patients were managed according to the peritoneal cancer index (PCI) by diagnostic laparoscopy. For patients with a PCI of >12, upfront IP and systemic chemotherapy were given. Patients with a PCI of ≤12 or reduced to ≤12 after upfront chemotherapy underwent CRS with HIPEC. The primary endpoints were safety and the recommended phase II dose (RP2D) confirmation for phase Ib and the 1-year overall survival rate for phase II.

The RP2D was defined as IP 175 mg/m2 paclitaxel and 60 mg/m2 cisplatin and oral 70 mg/m2/day S-1 for 14 days. A total of 22 patients were included. After CRS with HIPEC, there were no grade 3 or higher complications. The median hospital stay was 7 days (range, 6-11). The median overall and progression-free survival were 27.3 months (95% CI, 14.4 to not estimable) and 12.6 months (95% CI, 7.7-14.5), respectively. One-year overall and progression-free survival rates were 81.0% (95% CI, 65.8-99.6) and 54.5% (95% CI, 37.2-79.9), respectively.

A combination of IP plus systemic chemotherapy, CRS, and HIPEC was safe and resulted in good survival outcomes.

Many gastric cancer patients in Western countries are diagnosed as metastatic with a median overall survival of less than twelve months using standard chemotherapy. Innovative treatments, like targeted therapy or immunotherapy, have recently proved to ameliorate prognosis, but a general agreement on managing oligometastatic disease has yet to be achieved. An international multi-disciplinary workshop was held in Bertinoro, Italy, in November 2022 to verify whether achieving a consensus on at least some topics was possible.

A two-round Delphi process was carried out, where participants were asked to answer 32 multiple-choice questions about CT, laparoscopic staging and biomarkers, systemic treatment for different localization, role and indication of palliative care. Consensus was established with at least a 67% agreement.

The assembly agreed to define oligometastases as a "dynamic" disease which either regresses or remains stable in response to systemic treatment. In addition, the definition of oligometastases was restricted to the following sites: para-aortic nodal stations, liver, lung, and peritoneum, excluding bones. In detail, the following conditions should be considered as oligometastases: involvement of para-aortic stations, in particular 16a2 or 16b1; up to three technically resectable liver metastases; three unilateral or two bilateral lung metastases; peritoneal carcinomatosis with PCI ≤ 6. No consensus was achieved on how to classify positive cytology, which was considered as oligometastatic by 55% of participants only if converted to negative after chemotherapy.

As assessed at the time of diagnosis, surgical treatment of oligometastases should aim at R0 curativity on the entire disease volume, including both the primary tumor and its metastases. Conversion surgery was defined as surgery on the residual volume of disease, which was initially not resectable for technical and/or oncological reasons but nevertheless responded to first-line treatment.

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.

Peritoneal carcinomatosis is one of deadliest metastatic patterns of gastric cancer, being associated with a median overall survival (OS) of 4 months. Up to now, palliative systemic chemotherapy (pSC) has been the only recommended treatment. The aim of this study is to evaluate a potential survival benefit after CRS + HIPEC compared to pSC.

A systematic review was conducted according to the PRISMA guidelines in March 2024. Manuscripts reporting patients with peritoneal carcinomatosis from gastric cancer treated with CRS + HIPEC were included. A meta-analysis was performed, comparing the survival results between the CRS + HIPEC and pSC groups, and the primary outcome was the comparison in terms of OS. We performed random-effects meta-analysis of odds ratios (ORs). We assessed heterogeneity using the Q2 statistic.

Out of the 24 papers included, 1369 patients underwent CRS + HIPEC, with a median OS range of 9.8-28.2 months; and 103 patients underwent pSC, with a median OS range of 4.9-8 months. CRS + HIPEC was associated with significantly increased survival compared to palliative systemic chemotherapy (-1.8954 (95% CI: -2.5761 to -1.2146; p < 0.001).

CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC.

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.

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

Peritoneal metastasis is a common finding in patients with advanced gastric cancer. Beyond systemic chemotherapy, additive local treatments such as cytoreductive surgery and intraperitoneal chemotherapy are considered an inherent part of different multimodal treatment concepts for selected patients with peritoneal metastatic gastric cancer. This review article discusses the role of cytoreductive surgery (CRS) and intraperitoneal chemotherapy, including HIPEC, NIPS, and PIPAC, as additive therapeutic options with curative and palliative intent.

Hyperthermic intraperitoneal chemotherapy (HIPEC) associated with CC0 excision is performed using either an open (OPEN_HIPEC) or closed abdominal technique (CLOSED_HIPEC). However, little data is available on the costs of this treatment, as there is no code for HIPEC in the French Classification of Medical Acts. Oncological outcomes and the mean cost of hospitalization were compared.

Between 2017 and 2021, 144 patients with peritoneal carcinomatosis (all etiologies) were included (OPEN_HIPEC, n = 70; CLOSED_HIPEC, n = 74) in this retrospective two-center study. Morbi-mortality, overall survival (OS), recurrence-free-survival (RFS) and mean cost of hospitalization were compared.

The median OS and RFS were 71.3 months [63-71.5] and 26.8 months [20-35.3] respectively, and were similar for both techniques; and after stratification by histology. Multivariate analysis adjusted on PCI score of OS identified mitomycin as a protective factor (HR = 0.31 [0.10-0.90], p = 0.032) and ASA score>2 (HR = 2.32 [1.32- 4.06], p = 0.003) and number of resection (HR = 1.21 [1.06-1.39], p = 0.006) as a risk factors of RFS. Complication rates at day 30 were similar between OPEN and CLOSED_HIPEC, 31 (44.3 %) vs 42 (56.8 %); p = 0.135. OPEN_HIPEC had more severe complications (11 (35.5 %) vs 6 (14.3 %); p = 0.034). The mean cost of hospitalization was estimated as €15,627 for OPEN_HIPEC and €14,211 for CLOSED_HIPEC for a mean length-of-stay of 12.7 and 16.7 days respectively. The mean amount received by the hospital per hospitalization was estimated at €16,399 and €15,536 respectively.

OS and RFS were similar for open and closed HIPEC. Severe complications at day 30 were more frequent in OPEN_HIPEC group. The amount received by hospital for both HIPEC techniques is sufficient.

Hyperthermia, the raising of tumor temperature (≥39°C), holds great promise as an adjuvant treatment for cancer therapy. This review focuses on 2 key aspects of hyperthermia: its molecular and cellular effects and its impact on the immune system. Hyperthermia has profound effects on critical biological processes. Increased temperatures inhibit DNA repair enzymes, making cancer cells more sensitive to chemotherapy and radiation. Elevated temperatures also induce cell cycle arrest and trigger apoptotic pathways. Furthermore, hyperthermia modifies the expression of heat shock proteins, which play vital roles in cancer therapy, including enhancing immune responses. Hyperthermic treatments also have a significant impact on the body's immune response against tumors, potentially improving the efficacy of immune checkpoint inhibitors. Mild systemic hyperthermia (39°C-41°C) mimics fever, activating immune cells and raising metabolic rates. Intense heat above 50°C can release tumor antigens, enhancing immune reactions. Using photothermal nanoparticles for targeted heating and drug delivery can also modulate the immune response. Hyperthermia emerges as a cost-effective and well-tolerated adjuvant therapy when integrated with immunotherapy. This comprehensive review serves as a valuable resource for the selection of patient-specific treatments and the guidance of future experimental studies.