Spatially Resolved Niche and Tumor Microenvironmental Alterations in Gastric Cancer Peritoneal Metastases.

BACKGROUND & AIMS: Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, and tumor microenvironment (TME) features that contribute to peritoneal organotropism in GC. METHODS: We conducted a comprehensive multi-omic analysis of 548 samples from 326 patients, including primary tumors, matched normal tissues; peritoneal metastases, and adjacent-normal peritoneal tissues. We used whole exome sequencing, whole transcriptome sequencing, and digital spatial profiling to investigate molecular alterations, gene expression patterns, and TME characteristics associated with PM. RESULTS: Our analysis identified specific genomic alterations in primary tumors, including mutations in ELF3, CDH1, and PIGR, and TME signatures, such as stromal infiltration and M2 macrophage enrichment, associated with increased risk of PM. We observed distinct transcriptional programs and immune compositions in GCPM compared with liver metastases, highlighting the importance of the TME in transcoelomic metastasis. We found differential expression of therapeutic targets between primary tumors and PM, with lower CLDN18.2 and FGFR2b expression in PM. We unravel the roles of the TME in niche reprogramming within the peritoneum, and provide evidence of pre-metastatic niche conditioning even in early GC without clinical PM. These findings were further validated using a humanized mouse model, which demonstrated niche remodeling in the peritoneum during transcoelomic metastasis. CONCLUSION: Our study provides a comprehensive molecular characterization of GCPM and unveils key biological principles underlying transcoelomic metastasis. The identified predictive markers, therapeutic targets, and TME alterations offer potential avenues for targeted interventions and improved patient outcomes.

Postoperative Inflammatory Marker Surveillance in Colorectal Peritoneal Carcinomatosis.

BACKGROUND: The prognostic significance of inflammatory markers in solid cancers is well-established, albeit with considerable heterogeneity. This study sought to investigate the postoperative inflammatory marker trend in peritoneal carcinomatosis (PC), with a focus on colorectal PC (CPC), and to propose optimal surveillance periods and cutoffs. METHODS: Data were collected from a prospectively maintained database of PC patients treated at the authors' institution from April 2001 to March 2019. The platelet-lymphocyte ratio (PLR), the neutrophil-lymphocyte ratio (NLR), and the lymphocyte-monocyte ratio (LMR) were collected preoperatively and on postoperative days 0, 1 to 3, 4 to 7, 8 to 21, 22 to 56, and 57 to 90 as averages. Optimal surveillance periods and cutoffs for each marker were determined by maximally selected rank statistics. The Kaplan-Meier method and Cox proportional hazard regression models were used to investigate the association of inflammatory markers with 1-year overall survival (OS) and recurrence-free survival (RFS) using clinicopathologic parameters. RESULTS: The postoperative inflammatory marker trend and levels did not differ between the patients with and those without hyperthermic intraperitoneal chemotherapy (HIPEC). Low postoperative LMR (days 4-7), high postoperative NLR (days 8-21), and high postoperative PLR (days 22-56) were optimal for prognosticating poor 1-year OS, whereas high postoperative PLR and NLR (days 57-90) and low postoperative LMR (days 8-21) were associated with poor 1-year RFS. A composite score of these three markers was prognostic for OS in CPC. CONCLUSIONS: The reported cutoffs should be validated in a larger population of CPC patients. Future studies should account for the inflammatory response profile when selecting appropriate surveillance periods.

Retrospective quality of life study in patients with retroperitoneal sarcoma in an Asian population.

BACKGROUND: Retroperitoneal sarcoma represents 15% of sarcomas. The mainstay of treatment is surgery where a majority of patients require multi-visceral resections that may significantly impact their quality of life (QOL) following surgery. Studies in other cancers have shown that QOL may not be significantly impacted after radical or extensive surgery. However, there are limited studies examining the QOL specifically in patients with retroperitoneal sarcoma. In this pilot study, we retrospectively evaluated the QOL of patients with retroperitoneal sarcoma. METHODS: 32 out of 90 patients who underwent surgical intervention for retroperitoneal sarcoma in National Cancer Centre Singapore from January 1999 to August 2018 who were alive and on follow-up were included in this study. EORTC-QLQ-C30 was administered to the patients. RESULTS: The median age of our patients was 59 years (range, 35-84), and median time from surgery to the implementation of questionnaire was 2.5 years (range, 0.05-9.6). Younger patients had significantly better differences in global health, physical and role functioning scores as compared to older individuals. Female patients reported higher global health, physical, emotional and social functioning scores than males. Patients who were more than 2 years post-surgery exhibited better QOL scores as compared to those who had more recent surgery. Our patients had comparable global health and functioning scores compared to a reference group of outpatient cancer patients at our institution. CONCLUSIONS: Our pilot study investigating the QOL of patients with retroperitoneal sarcoma has shown that patients need to be followed up for at least 2 years following surgery to evaluate their QOL. In general, they achieved better functioning scores when compared with other cancer patients. These findings support the need for larger-scale prospective studies to further evaluate the QOL of these patients.

High-grade complication is associated with poor overall survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used in peritoneal carcinomatosis (PC) management. This modality is criticized for its high morbidity and mortality. We evaluate the morbidity and mortality of patients undergoing this procedure in our institution. METHODS: A review of our institution's database was performed. All patients who underwent CRS/HIPEC between July 2011 and March 2018 were divided into three groups: no, low-grade, and high-grade complications. Prognostic factors were determined with Cox regression, while morbidity risk factors were analyzed using multinomial logistic regression. RESULTS: 225 consecutive patients underwent CRS/HIPEC. The most common primary cancer types were colorectal (35.1%), appendiceal (25.8%), and ovarian (22.2%). Median age was 55 years old (range 14-77), and patients were typically female (68.0%). 38.7% developed low-grade complications and 14.7% had high-grade complications. No 30-day mortality was observed. Different tumor origins are associated with significant differences in overall survival (p < 0.001). Patients without complications had significantly better survival than those with high-grade complications (HR 0.35, 95% CI 0.15-0.81, p < 0.001). Males were more likely to develop low-grade complications (OR 3.30, 95% CI 1.31-8.30, p = 0.011). Intra-operative blood loss was associated with greater odds of developing any post-operative complications (OR 1.001, 95% CI 1.0003-1.002, p = 0.007; and OR 1.002, 95% CI 1.001-1.002, p < 0.001, for low and high grade, respectively). CONCLUSION: Presence of high-grade complication was associated with poorer survival in patients after CRS/HIPEC. Pre-operative careful assessment of patients is pivotal to ensure favorable patient outcome following this complex procedure.

Docosahexaenoic acid and L-Carnitine prevent ATP loss in SH-SY5Y neuroblastoma cells after exposure to silver nanoparticles.

Silver nanoparticles (AgNPs) are among the most commonly used nanomaterials, but thus far, little is known about ways to mitigate against potential toxic effects of exposure. In this study, we examined the potential effects of AgNPs on mitochondrial function and cellular ATP levels, and whether these could be prevented by treatment with docosahexaenoic acid (DHA) and L-carnitine (LC). Acute exposure of AgNPs for 1 h to SH-SY5Y cells resulted in decreased mitochondrial membrane potential, and decreased ATP and ADP levels, indicating mitochondrial damage and reduced production of ATP. Incubation of cells with DHA partially reduced, while treatment with LC and DHA completely abolished the AgNP induced decreases in ATP and ADP levels. This could be due to a LC-facilitated entry of DHA to mitochondria, for repair of damaged phospholipids. It is postulated that DHA and LC may be useful for treatment of accidental environmental exposure to AgNPs.

Food Matrix Composition Affects the Allergenicity of Baked Egg Products.

BACKGROUND: Egg allergy is common and caused by sensitization to ovomucoid and/or ovalbumin. Many egg-allergic patients are able to tolerate eggs baked into other foods, such as muffins. Although heating egg extensively reduces allergens, the effect of other food ingredients on allergenicity of eggs, or the "matrix effect," is less well studied. OBJECTIVE: We aimed to define how food matrices impact the matrix effect in egg allergenicity. METHODS: Enzyme-linked immunosorbent assay was used to quantify ovalbumin and ovomucoid in extracts from various baked egg products: plain baked egg without a matrix, and muffins baked using either wheat flour, rice flour, or a wheat flour/banana puree mix. Allergen-specific immunoglobulin E (IgE)-blocking enzyme-linked immunosorbent assays were performed using the egg product extracts on egg-allergic patient sera to determine whether the amount of extracted egg protein in each extract correlated with how well the extracts could bind patients' egg IgE. RESULTS: Baking eggs in any muffin matrix led to an increase in the amount of extractable ovalbumin and a decrease in the amount of extractable ovomucoid compared with plain baked egg. Compared with wheat muffins, rice muffins had more extractable ovalbumin and wheat/banana muffins had more extractable ovalbumin and ovomucoid. The egg allergens in the extracts were able to block egg-allergic patients' egg IgE. CONCLUSIONS: Food matrices affect egg allergen availability. Patients and families should be advised that substitutions in baked egg muffin recipes can affect the amount of egg allergens in foods and potentially affect the risk of food allergic reaction.

Radical resection and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of high risk recurrent retroperitoneal sarcoma-A pilot study in a tertiary Asian centre.

BACKGROUND: Peritoneal sarcomatosis (PS) is a difficult entity to treat with limited options and guarded prognosis. We aimed to determine if the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) could offer superior local recurrence-free survival in patients with retroperitoneal sarcoma at high risk of developing PS as opposed to extended resection alone. METHODS: This is a single arm, phase II intervention study where all patients with recurrent localized retroperitoneal sarcoma considered at high risk of developing PS were considered for enrolment (ClinicalTrials.gov identifier: NCT03792867). Upon enrolment, patients underwent vigorous preoperative testing to ensure fitness for the procedure. During surgery, patients underwent extended resection and HIPEC with doxorubicin. Patients were followed-up every 2 weeks (± 10 days) for the first month and subsequently every three months (± 1 month) up to a year post-surgery, and were assessed for potential chemotherapy toxicity and post-treatment complications. After a year from resection and HIPEC, patients were followed-up either during routine clinic review or contacted via telephone every year (± 1 month) for 3 years. RESULTS: Six patients were recruited but one patient dropped out due to adverse and unexpected intraoperative events. The remaining patients completed the procedure uneventfully. Post-HIPEC, all patients recurred with a disease-free interval ranging from six to 24 months. Three patients died due to complications from recurrent disease whereas the remaining three patients are alive as of their last visit. The overall survival at time at reporting ranged between 22 to 56 months. CONCLUSION: The procedure is feasible with no major morbidity to patients. However, we are unable to recommend for it to be implemented as a routine procedure at this current stage due to lack of improved survival outcomes. Further multi-institutional studies may be conducted to yield better results.

The immunomodulatory role of paracrine signalling factor VSIG4 in peritoneal metastases.

Peritoneal metastasis (PM), the regional progression of intra-abdominal malignancies, is a common sequelae of colorectal cancer (CRC). Immunotherapy is slated to be effective in generating long-lasting anti-tumour response as it utilizes the specificity and memory of the immune system. In the tumour microenvironment, tumour associated macrophages (TAMs) are posited to create an anti-inflammatory pro-tumorigenic environment. In this paper, we aimed to identify immunomodulatory factors associated with colorectal PM (CPM). A publicly available colorectal single cell database (GSE183916) was analysed to identify possible immunological markers that are associated with the activation of macrophages in cancers. Immunohistochemical analysis for V-set and immunoglobin containing domain 4 (VSIG4) expression was performed on tumour microarrays (TMAs) of tumours of colorectal origin (n = 211). Expression of VSIG4 in cell-free ascites obtained from CPM patients (n = 39) was determined using enzyme-linked immunosorbent assay (ELISA). CD163-positive TAMs cluster expression was extracted from a publicly available single cell database and evaluated for the top 100 genes. From these macrophage-expressed genes, VSIG4, a membrane protein produced by the M2 macrophages, mediates the up-regulation of anti-inflammatory and down-regulation of pro-inflammatory macrophages, contributing to an overall anti-inflammatory state. CRC TMA IHC staining showed that low expression of VSIG4 in stromal tissues of primary CRC are associated with poor prognosis (p = 0.0226). CPM ascites also contained varying concentrations of VSIG4, which points to a possible role of VSIG4 in the ascites. The contribution of VSIG4 to CPM development can be further evaluated for its potential as an immunotherapeutic agent.

Transcriptomic convergence despite genomic divergence drive field cancerization in synchronous squamous tumors.

Introduction: Field cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that eventually replace the epithelium, although without evidence. Methods: We performed deep sequencing analyses to characterize the genomic and transcriptomic landscapes of field change in two patients with synchronous aerodigestive tract tumors. Results: Our data support the emergence of numerous genetic alterations in cancer-associated genes but refutes the hypothesis that founder mutation(s) underpin this phenomenon. Mutational signature analysis identified defective homologous recombination as a common underlying mutational process unique to synchronous tumors. Discussion: Our analyses suggest a common etiologic factor defined by mutational signatures and/or transcriptomic convergence, which could provide a therapeutic opportunity.

Preptin Deficiency Does Not Protect against High-Fat Diet-Induced Metabolic Dysfunction or Bone Loss in Mice.

Preptin is derived from the cleavage of the E-peptide of pro-insulin-like growth factor (IGF)-II and is an insulin secretagogue. Observational studies have linked elevated circulating preptin to metabolic dysfunction in humans; however, a causal role for preptin in metabolic dysfunction has not been established. Additionally, preptin can promote osteoblast proliferation and differentiation, suggesting a link with skeletal health. We previously described a global preptin knockout (KO) model. In this study, we sought to uncover the impact of preptin KO in mice on the response to a moderately high-fat diet (HFD) and low-fat diet (LFD). HFD groups had higher weight and fat mass gain, lower trabecular and cortical bone volume and fracture load, and higher liver triglycerides. In males, preptin deficiency led to lower blood glucose than wild-type (WT) mice under LFD conditions. This was accompanied by differences in bone microarchitecture, including lower trabecular bone volume fraction, trabecular number, and lower cortical thickness. These differences were absent in female mice, although KO females had a HFD-driven increase in fat mass and liver triglycerides that was absent in WT mice. Female WT mice had increased glucose-stimulated insulin secretion under HFD conditions that was absent in female KO mice. Overall, preptin may have a detrimental impact on metabolism and a positive impact on bone health in male mice and may protect against liver fat storage in females while enabling islet compensation under HFD conditions. When we consider that serum preptin levels are elevated in humans of both sexes in pathological states in which insulin levels are elevated, the impact of preptin on comorbidity risk needs to be better understood. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A Systematic Review and Meta-Analysis of Mapping Biopsy for Primary Extramammary Paget's Disease in Reducing Recurrence Following Surgical Excision.

Objective: To examine the association between the performance of mapping biopsies and surgical outcomes postexcision of extramammary Paget's disease (EMPD). Background: Primary EMPD is a rare entity associated with poorly defined surgical margins and difficult-to-access sites of lesions. Surgical resection with clear margins remains the preferred management method. The use of mapping biopsies might be beneficial, particularly in lowering disease recurrence. Methods: Available literature was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology before a fixed-effect meta-analysis was performed to identify the presence of a correlation between performing mapping biopsies and positive margins on permanent sections as well as disease-free survival. Additional study results not included in the quantitative assessment were qualitatively assessed and reported. Results: A total of 12 studies were shortlisted for final analysis. 294 patients who underwent mapping biopsies and 48 patients who did not undergo mapping biopsies were included in the assessment. Forest plot analysis revealed a pooled rate ratio of 0.50 (95% CI, 0.32-0.77) in the prevalence of positive margins in patients with mapping biopsies performed as compared to patients without. The pooled rate ratio of the prevalence of disease-free survival in patients with mapping biopsies performed as compared to patients without was 1.38 (95% CI, 1.03-1.84). Qualitative assessment of the remaining selected studies revealed equivocal results. Conclusions: Mapping biopsies are able to improve EMPD surgical excision outcomes but given the rarity of the disease and heterogeneity of mapping biopsy procedures, further confirmation with randomized controlled trials or a larger patient pool is necessary.

A systematic review of margin status in retroperitoneal liposarcomas: Does the R0 margin matter?

Retroperitoneal liposarcomas (RPLPSs) are a rare tumor group for which current guidelines recommend aggressive en bloc resection to attain microscopically negative (R0) margins. To ensure R0 margins, resection of adherent or adjacent organs is often required. However, it is still unclear if R0 margins confer any additional benefit to patients over a grossly negative but microscopically positive (R1) margin. We performed a systematic search of PubMed and Embase databases for studies including patients receiving R0 or R1 resection for RPLPS. Nine retrospective cohort studies, one prospective cohort study, and 49 case reports/case series were included. A total of 552 patients with RPLPS were evaluated: 346 underwent R0 resection and 206 underwent R1 resection. In the R0 group, 5-year overall survival (OS) ranged from 58.3% to 85.7%; local recurrence (LR) ranged from 45.5% to 52.3%. In the R1 group, 5-year OS ranged from 35% to 55.3%; LR ranged from 66.7% to 91.7%. Among cohort studies, OS, disease-free survival (DFS), LR rate, and LR-free survival (LRFS) were significantly associated with R0 resections. Assessment of case series and reports suggested that the R0 margin led to a slightly higher morbidity than that of R1. In conclusion, this review found the R0 margin to be associated with reductions in LR rates and improved OS when compared with the R1 margins, though accompanied by slight increases in morbidity. The roles of tumor histotype and perioperative chemotherapy or radiotherapy were not well-elucidated in this review.

A systematic review on quality of life (QoL) of patients with peritoneal metastasis (PM) who underwent pressurized intraperitoneal aerosol chemotherapy (PIPAC).

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has recently emerged as a palliative alternative for patients with unresectable peritoneal metastasis (PM). Quality of life (QoL) has increasingly been used as an endpoint to evaluate treatment outcomes. This review aims to identify evidence on how PIPAC would impact the QoL of PM patients. Content: A systematic review was performed on articles identified from Medline, EMBASE, PsycInfo, and Web of Sciences. A meta-analysis was conducted on further selected studies. ACROBAT-NRSI was attempted to assess the risk of bias (RoB). Summary: Nine studies using the EORTC QLQ-C30 questionnaire to assess QoL after repeated PIPAC cycles were identified. Majority was found to be moderately biased and a great extent of heterogeneity was observed. Four studies on PM from either gastric cancer (GC) or epithelial ovarian cancer (EOC) were included for meta-analysis. In 31 GC patients and 104 EOC patients, QoL remained stable in 13/14 and 11/14 EORTC QLQ-C30 scales. PIPAC was inferior to cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in global QoL and functioning but superior in symptom reduction. Outlook: PIPAC is a well-tolerated option for most GC and EOC patients with irresectable PM. Future trials are warranted to confirm the findings.

Generating patient-derived ascites-dependent xenograft mouse models of peritoneal carcinomatosis.

Clinically relevant animal models are crucial for effective development of therapeutics for peritoneal carcinomatosis (PC). This protocol describes the generation of patient-derived ascites-dependent xenograft (PDADX) models from the cellular component of ascites. The use of routine intraperitoneal injection of the fluid component of ascites is analogous to the biological events occurring intra-abdominally in patients with PC. By serving as a proxy, PDADX models represent a valuable tool for preclinical testing of new therapeutics for PC. For complete details on the use and execution of this protocol, please refer to Hendrikson et al. (2022).

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal sarcomatosis-A systematic review and meta-analysis.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) play an important role in the treatment of various peritoneal surface malignancies, but its efficacy in peritoneal sarcomatosis (PS) remains unknown. Hence, we performed a systematic review and meta-analysis to investigate outcomes of CRS-HIPEC in PS, in accordance with PRISMA guidelines. 16 studies with a total of 320 patients were included in the meta-analysis. Pooled mean length of hospital stay after CRS-HIPEC was 16.0 days (95% CI: 12.2-19.8) and rate of serious complications was 17.4% (95% CI: 9.8-26.3). The median DFS was 12.0 months (95% CI: 8.0-16.0) and the 5-year DFS was 21.8% (95% CI: 13.2-31.7). Overall pooled median OS was 29.3 months (95% CI: 23.8-34.8), with a 5-year OS of 35.3% (95% CI: 26.3-44.8). Subgroup analysis showed that patients with CC-0 cytoreduction had a higher median OS of 34.6 months (95% CI: 23.2-45.9). Median OS for patients with a primary tumour histology of leiomyosarcoma and liposarcoma was 33.5 months (95% CI: 15.9-51.1) and 39.1 months (95% CI: 20.8-57.5) respectively. The site of recurrence was locoregional in 57.3% (95% CI: 38.9-74.8), distant in 17.3% (95% CI: 3.9-35.6), and both in 17.4% (95% CI: 5.8-32.2). In conclusion, our results suggest that CRS-HIPEC may improve outcomes in a select group of PS patients.

Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis.

Peritoneal carcinomatosis (PC) present a ubiquitous clinical conundrum in all intra-abdominal malignancies. Via functional and transcriptomic experiments of ascites-treated PC cells, we identify STAT3 as a key signaling pathway. Integrative analysis of publicly available databases and correlation with clinical cohorts (n = 7,359) reveal putative clinically significant activating ligands of STAT3 signaling. We further validate a 3-biomarker prognostic panel in ascites independent of clinical covariates in a prospective study (n = 149). Via single-cell sequencing experiments, we uncover that PAI-1, a key component of the prognostic biomarker panel, is largely secreted by fibroblasts and mesothelial cells. Molecular stratification of ascites using PAI-1 levels and STAT3 activation in ascites-treated cells highlight a therapeutic opportunity based on a phenomenon of paracrine addiction. These results are recapitulated in patient-derived ascites-dependent xenografts. Here, we demonstrate therapeutic proof of concept of direct ligand inhibition of a prognostic target within an enclosed biological space.

A rare case of retroperitoneal lymphangioma in a 74-year-old Chinese male.

Retroperitoneal lymphangioma is an uncommon and benign mesodermal tumour that arises from the retroperitoneal lymphatics. Notably, it is a rare occurrence in adults, where <200 adult retroperitoneal lymphangioma cases have been published in the literature. Additionally, retroperitoneal lymphangioma is often difficult to diagnose preoperatively and formal diagnosis is frequently determined following surgical exploration. Here, we describe a rare case of retroperitoneal lymphangioma in a 74-year-old man who presented with a 6-month history of intermittent fresh per rectal bleeding with an incidental non-tender left iliac fossa firm mass on examination. Computed tomography scan established a retroperitoneal cystic lesion abutting the aorta and left common iliac vessels. Surgical exploration revealed a large cystic mass and a clean plane of dissection was performed, where the mass was completely excised with all the key structures preserved. Histology was consistent with a retroperitoneal lymphangioma.

Effect of HIPEC on Peritoneal Recurrence in Peritoneal Metastasis Treated With Cytoreductive Surgery: A Systematic Review.

BACKGROUND: Peritoneal metastasis (PM) is a late-stage manifestation of intra-abdominal malignancies. The current standard of care indicates that cure can only be achieved with cytoreductive surgery (CRS) which is often indicated with concurrent adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC). However, the utility of HIPEC within subsets of PM is not fully understood. We seek to compare the effectiveness of HIPEC in improving peritoneal recurrence rates in PM of different origins. METHODS: We conducted a systematic review of trials on the PubMed, EMBASE, and Cochrane databases, last searched in August 2021. Biases were assessed using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials as well as the Methodological Index for Non-Randomized Studies (MINORS) framework. RESULTS: 7 gastric PM studies, 3 ovarian PM studies, and 3 colorectal PM studies were included. Recurrence-free survival was improved in the HIPEC + CRS cohort in 5 gastric trials but only 1 ovarian trial and none of colorectal origin. DISCUSSION: Our findings indicate decent effectiveness of HIPEC in gastric PM, but limited utility in ovarian and colorectal PM. Limitations in the current literature are attributed to the paucity of data available, a lack of homogeneity and consideration of novel and personalised treatment regimens. We implore for further studies to be conducted with a focus on patient selection and stratification, and suggest a reframing of approach towards modern molecular and targeted therapeutic options in future studies of HIPEC. SYSTEMATIC REVIEW REGISTRATION: https://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmeta-analyses/registryofsystematicreviewsmeta-analysesdetails/60c1ffff0c1b78001e8efbe3/, identifier reviewregistry1166.

The Role of Total Parenteral Nutrition in Patients with Peritoneal Carcinomatosis: A Systematic Review and Meta-Analysis.

Peritoneal carcinomatosis (PC) is often associated with malnutrition and an inability to tolerate enteral feeding. Although total parenteral nutrition (TPN) can be lifesaving for patients with no other means of nutritional support, its use in the management of PC patients remains controversial. Therefore, a systematic review and meta-analysis was performed to evaluate the benefit of TPN on the overall survival of PC patients, in accordance with PRISMA guidelines. A total of 187 articles were screened; 10 were included in this review and eight were included in the meta-analysis. The pooled median overall survival of patients who received TPN was significantly higher than patients who did not receive TPN (p = 0.040). When only high-quality studies were included, a significant survival advantage was observed in PC patients receiving TPN (p < 0.001). Subgroup analysis of patients receiving chemotherapy demonstrated a significant survival benefit (p = 0.008) associated with the use of TPN. In conclusion, TPN may improve survival outcomes in PC patients. However, further studies are needed to conclude more definitively on the effect of TPN.