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Introduction: Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy has become standard for resectable peritoneal surface malignancies. CRS aims to achieve complete resection of macroscopic disease through peritonectomy procedures and visceral resections. The pelvis is very frequently involved in peritoneal malignancies, making surgical techniques that ensure complete tumor removal an essential part of CRS. This is best achieved through an en bloc pelvic peritonectomy, which frequently includes a hysterectomy and bilateral oophorectomy in women., Methodology: We created a video to review technical steps and exposure tips to achieve a complete cytoreduction of the pelvis in female patients with en bloc resection of the entire pelvic peritoneum, including the cul-de-sac, the uterus, and the adnexa, with ('classic pelvic peritonectomy') or without ('visceral-sparing pelvic peritonectomy') rectosigmoid resection. The creation of a protective ileostomy in classic pelvic peritonectomy is routine in many centers, while other centers advocate only selective and sparing use of ileostomy. In our center, protective ileostomy is used selectively and is therefore not included in the video., Results: In the first part of the video, we review the rationale, indications, and steps, while in the second part, we show a practical demonstration of both a classic and a visceral-sparing pelvic peritonectomy in female patients., Conclusion: Complete pelvic peritonectomy can be achieved both with or without en bloc resection of the rectosigmoid colon. This technique is an essential part of CRS, and mastery of the technique can help the likelihood of achieving complete tumor removal in advanced or complex involvement of the pelvis., Competing Interests: Disclosure: Julian Henao Ardila, Domenico Sabia, Marina Bosch Ramirez, Jaume Tur Martinez, Santiago Gonzalez Moreno, Vadim Gushchin, Thanh Dellinger, and Lana Bijelic report no conflicts of interest that may be relevant to the contents of this article., (© 2024. Society of Surgical Oncology.)

The small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial-mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1-SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1-SUMO1. POTEE activates Rac1 in the invadopodium by recruiting TRIO-GEF (triple functional domain protein), and it induces tumor cell proliferation and metastasis in vitro and in vivo. We found that the co-localization of POTEE with Rac1 is correlated with more aggressive breast cancer subtypes. Given its role in tumor dissemination, the leading cause of cancer-related deaths, POTEE could represent a potential therapeutic target for these types of cancer., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Molecular mechanisms that regulate tumor-associated macrophage (TAM) phenotype and function are incompletely understood. The pseudokinase TRIB1 has been reported as a regulator of macrophage phenotypes, both in mouse and human systems. Methods: Bioinformatic analysis was used to investigate the link between TRIB1 expression in breast cancer and therapeutic response to chemotherapy. In vivo models of breast cancer included immune-competent mice to characterize the consequences of altered (reduced or elevated) myeloid Trib1 expression on tumor growth and composition of stromal immune cell populations. Results: TRIB1 was highly expressed by TAMs in breast cancer and high TRIB1 expression correlated with response to chemotherapy and patient survival. Both overexpression and knockout of myeloid Trib1 promote mouse breast tumor growth, albeit through different molecular mechanisms. Myeloid Trib1 deficiency led to an early acceleration of tumor growth, paired with a selective reduction in perivascular macrophage numbers in vivo and enhanced oncogenic cytokine expression in vitro . In contrast, elevated levels of Trib1 in myeloid cells led to an increased late-stage mammary tumor volume, coupled with a reduction of NOS2 expressing macrophages and an overall reduction of macrophages in hypoxic tumor regions. In addition, we show that myeloid Trib1 is a previously unknown, negative regulator of the anti-tumor cytokine IL-15, and that increased myeloid Trib1 expression leads to reduced IL-15 levels in mammary tumors, with a consequent reduction in the number of T-cells that are key to anti-tumor immune responses. Conclusions: Together, these results define a key role for TRIB1 in chemotherapy responses for human breast cancer and provide a mechanistic understanding for the importance of the control of myeloid TRIB1 expression in the development of this disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

(1) Background: Peritoneal metastasis in gastric cancer is associated with a poor prognosis. Complete cytoreductive surgery including gastrectomy and complete removal of all peritoneal lesions followed by hyperthermic intraperitoneal chemotherapy (HIPEC) achieves promising results. There exists an immersive variety of approaches for HIPEC that makes it difficult to weigh different results obtained in the literature. In order to enable standardization and development of HIPEC, we here present a systematic review of different drug regimens and technical approaches. (2) Methods: PubMed, Embase, and the Cochrane Library were systematically searched on 26 May 2021 using the mesh terms "intraperitoneal chemotherapy AND gastric cancer". Under consideration of systematic review guidelines, articles reporting on HIPEC in combination with CRS were selected. Data on duration, drugs, dosage, and other application parameters as well as morbidity and long term survival data were extracted for subsequent statistical analysis, tabulation, and descriptive synthesis. We assessed the risk of bias due to inhomogeneity of the patient cohort and incompleteness of report of HIPEC parameters. (3) Results: Out of 1421 screened publications, 42 publications presenting data from 1325 patients met the criteria. Most of the publications were single institutional retrospective cohort studies. The most common HIPEC regimen is performed after gastrointestinal anastomosis and consists of 50-200 mg/m 2 cisplatinum and 30-40 mg/m 2 mytomycin C at 42-43 °C for 60-90 min in a closed abdomen HIPEC system with three tubes. Almost every study reported incompletely on HIPEC parameters. Lower rates of anastomotic leakage were reported in studies that performed HIPEC after gastrointestinal anastomosis. Studies that performed open HIPEC and integrated a two-drug regimen indicated better overall survival rates. (4) Discussion: This is an exhaustive overview of the use of drug regimens and techniques for HIPEC after CRS for gastric cancer peritoneal metastasis. Other indications and application modes of intraperitoneal chemotherapy such as prophylactic or palliative HIPEC apart from CRS were not addressed. (5) Conclusion: Complete report of HIPEC parameters should be included in every publication. A consensus for dose expression either per BSA or as flat dose is desirable for comparison of the drug regimens. Despite numerous variations, we identified the most common regimens and techniques and their advantages and disadvantages according to the data in the literature. More phase I/II studies are needed to identify the best approach for HIPEC. (6) Other: This review was not supported by third parties.

Introduction: Surgical oncology is a defined specialty within the European Board of Surgery within the European Union of Medical Specialists (UEMS). Variation in training and specialization still occurs across Europe. There is a need to align the core knowledge needed to fulfil the criteria across subspecialities in surgical oncology., Material and Methods: The core curriculum, established in 2013, was developed with contributions from expert advisors from within the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO) and European Society of Medical Oncology (ESMO) and related subspeciality experts., Results: The current version reiterates and updates the core curriculum structure needed for current and future candidates who plans to train for and eventually sit the European fellowship exam for the European Board of Surgery in Surgical Oncology. The content included is not intended to be exhaustive but, rather to give the candidate an idea of expectations and areas for in depth study, in addition to the practical requirements. The five elements included are: Basic principles of oncology; Disease site specific oncology; Generic clinical skills; Training recommendations, and, lastly; Eligibility for the EBSQ exam in Surgical Oncology., Conclusions: As evidence-based care for cancer patients evolves through research into basic science, translational research and clinical trials, the core curriculum will evolve, mature and adapt to deliver continual improvements in cancer outcomes for patients., Competing Interests: Declaration of Competing Interest There are no conflicts of interest reported., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The majority of cancer patients report malnutrition, with a significant impact on patient's outcome. This study aimed to compare how nutritional assessment is conducted across different surgical oncology sub-specialties., Methods: Survey modules were designed for breast, hepato-pancreato-biliary (HPB), upper-gastrointestinal (UGI), sarcoma, peritoneal and surface malignancies (PSM) and colorectal cancer (CRC) surgeries to describe 4 domains: participants' setting, evaluation of clinical factors, use of screening tools and clinical practice. Results were compared among sub-specialties and according to human development index (HDI) in the largest cohorts., Results: Out of 457 answers from 377 global participants (62% European), 35.0% were from breast and 28.9% were from CRC surgeons. Although MDTs management is consistently reported (64-88%), the presence of a nutritionist/dietician ranges from 14.1% to 44.2%. Breast surgeons seldom evaluate albumin (25.6%) and weight loss (30.6%), opposite to HPB, PSM and UGI groups (>70%, p 0.044). Overall, responders declared that the use of screening tools is largely neglected, that nutritional status is often assessed by the surgeons and that nutrition is not consistently modified according to risk factors (range among groups respectively: 1.9%-25.6%, 33.1%-51.4%, 33.1%-60.5%). Less than 20% of breast surgeons assess patients before/after surgery, comparing to >60% of PSM surgeons. However, no statistical differences were documented comparing groups for the majority of the items of the 4 domains. Nutritional evaluation is more often conducted by breast surgeons in medium/low HDI countries comparing very high/high HDI (p 0.04)., Conclusions: Nutritional assessment is largely neglected. These results identify target-issues for the implementation of clinical practice., Competing Interests: Declaration of competing interest None of the authors has any potential financial conflict of interest related to this manuscript., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Colorectal cancer mortality presents world-wide variation. In rectal cancers presenting a complete/nearly-complete tumor response (ypT0/ypTis) following neoadjuvant treatment, the features correlated to nodal metastases and relapses still need to be defined., Methods: An international cohort study enrolling ypT0/ypTis rectal cancers surgically treated from 2012 to 2017 was conducted. A propensity matching was used to balance nodal-positive and nodal-negative patients and statistical analyses were performed to investigate survivals, using a bootstrap model for internal validation. The features correlated with nodal metastasis were studied. Countries with participating centers were ranked using the World Bank (WBI), Human Development (HDI) and Global Gender Gap (GGG) indexes to compare survivals., Results: 680 ypT0/ypTis from 52 European, Australian, Indian and American Institutions were analyzed. Mean follow-up was of 30.4 months. 96.5% were treated with total mesorectal excision, 7.2% were nodal-positive and 8.8% relapsed. Distal cancers (HR 0.71 95%CI: 0.56-0.91) and nodal metastasis and nodal metastasis (HR 3.85 95%CI:1.12-13.19) correlated with worse DFS, whereas a younger age was of borderline significance (HR 0.95 95%CI:0.91-0.99). The bootstrap analysis validated the model on 5000 repetitions. A short-course radiotherapy (OR 0.18 95%CI:0.09-0.37) correlated with the occurrence of nodal metastasis. Those countries classified in the low/medium-WBI, medium-HDI and lower-GGG ranks documented worse DFS curves (respectively p < 0.0001, p < 0.0001 and p 0.0002). However, the clinical stages were similar and patients from medium-HDI countries received more adjuvant chemotherapy than the others (p < 0.0001)., Conclusion: Sub-groups at risk for relapses and nodal metastasis were identified. A global variation exists also when benchmarking a rectal cancer complete regression., Competing Interests: Declaration of competing interest None of the authors has any potential financial conflict of interest related to this manuscript., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) has poor survival. Multi-modal treatment including systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) can be used in selected patients with curative intent. The majority published works consider PC of CRC origin as a homogenous disease. Aim of this study is to stress the different biological behaviors and survival of PC according to colonic or rectal origin., Methods: Data of CRS and HIPEC procedures for PC of CRC origin performed at MD Anderson Cancer Center-Madrid (Spain) have been collected, dividing patients into two groups according to colonic or rectal PC. Clinical, operatory, and postoperatory variables of the two groups have been analyzed to compare survival-related rates and PC origin., Results: In the years 2004-2015, 114 procedures of CRS followed by HIPEC for peritoneal metastasis of different origin have been performed; of these, 36 procedures were for colorectal PC (31 patients in colonic and 5 in rectal group). Two groups are homogenous after analysis of clinical, operatory, and follow-up data. Median survival (OS) is significantly higher in colonic compared to rectal group (47.83 vs. 22.0 months, p 0.008). 3- and 5-year survival rate is 74 and 50% in colonic group vs. 20 and 0% in rectal group., Conclusion: Rectal origin PC has a more aggressive behavior compared to colonic origin, reflecting in a worst prognosis of patients affected by rectal origin PC. According to our data and literature, indications of multi-modal treatment including CRS and HIPEC should be more restrictive for rectal cancer PC. Authors should differentiate colonic and rectal origin of PC when reporting cases in the literature.

Aim: The treatment of peritoneal surface malignancies ranges from palliative care to full cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy, HIPEC. Ongoing monitoring of patient recruitment and volume is usually carried out through dedicated registries. With multiple registries available worldwide, we sought to investigate the nature, extent and value of existing worldwide CRS and HIPEC registries., Methods: A questionnaire was sent out to all known major treatment centres. The questionnaire covers: general purpose of the registry; inclusion criteria in the registry; the date the registry was first established; volume of patients in the registry and description of the data fields in the registries. Finally, the population size of the catchment area of the registry was collected., Results: Twenty-seven questionnaires where returned. National databases are established in northwest European countries. There are five international general databases. Most database collect data on patients who have undergone an attempt to CRS and HIPEC. Two registries collect data on all patients with peritoneal carcinomatosis regardless the treatment. Most registries are primarily used for tracking outcomes and complications. When correlating the number of cases of CRS and HIPEC that are performed to the catchment area of the various registry, a large variation in the number of performed procedures related to the overall population was noted, ranging from 1.3 to 57 patients/million year with an average of 15 patients/1 million year., Conclusions: CRS and HIPEC is a well-established treatment for peritoneal surface malignancies worldwide. However, the coverage as well as the registration of treatment procedures differs widely. The most striking difference is the proportion of HIPEC procedures per capita which ranges from 1.3 to 57 patients per million. This suggests either a difference in patient selection, lack of access to HIPEC centres or lack of appropriate data collection.

The epithelial appendiceal neoplasms are uncommon and are usually detected as an unexpected surgical finding. The general surgeon should be aware of the diversity of its clinical manifestations and biological behaviors along with the significance of the surgical treatment on the progression of the illness and the prognosis of the patients. The operative findings and, especially, tumor histology, determine the type of surgery. Intestinal histologic subtype behaves and should be treated similarly to the right colon neoplasms; while mucinous tumors, often discordant between histology and its aggressiveness, can be treated with a simple appendectomy or require complex oncological surgeries. Mucinous tumors are often associated with the presence of mucin or tumor implants in the abdominal cavity, being the clinical syndrome known as pseudomyxoma peritonei (PMP). PMP tends to present an indolent but deadly evolution and requires a multimodal approach as a single treatment with curative potential: complete cytoreductive surgery plus hyperthermic Intra-peritoneal chemotherapy (CCRS + HIPEC) now considered the standard of care in this pathology. The general surgeon should be aware of the governing principles of the treatment of appendiceal neoplasms with or without peritoneal dissemination, know the therapeutic frontiers in every situation (avoiding unnecessary or counterproductive surgeries) and sending early these patients to specialised centres in the radical management of malignant diseases of the peritoneum in the conditions and with the necessary information to facilitate a possible radical treatment.

Tumor involvement of the peritoneum-peritoneal carcinomatosis-is a heterogeneous form of cancer that had been generally regarded as a sign of systemic tumor disease and as a terminal condition. The multimodal treatment approach for patients with peritoneal carcinomatosis, which had been conceived and developed, consists of what is known as cytoreductive surgery, followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Depending on the tumor mass as assessed intraoperatively and the histopathological differentiation, patients who undergo cytoreductive surgery and HIPEC have a significant survival benefit. Mean increases in the survival period ranging from six months to up to four years have now been reported. In view of the substantial logistic effort and the extent of the surgery involved, this treatment approach represents a major challenge both for patients and for surgical oncologists, as well as for the members of the overall interdisciplinary structure required, which includes oncology, anesthesiology and intensive care, psycho-oncology, and patient management. The surgical procedures alone may take 8-14 hr. The present paper provides an overview of the basis for the approach and the use of specialized classifications and quantitative prognostic indicators.

Background: Evaluation of peritoneal metastases by computed tomography (CT) scans is challenging and has been reported to be inaccurate., Methods: A multi-institutional prospective observational registry study of patients with peritoneal carcinomatosis from colorectal cancer was conducted and a subset analysis was performed to examine peritoneal cancer index (PCI) based on CT and intraoperative exploration., Results: Fifty-two patients (mean age 52.6 ± 12.4 years) from 16 institutions were included in this study. Inaccuracies of CT-based assessment of lesion sizes were observed in the RUQ (P = 0.004), LLQ (P < 0.0005), RLQ (P = 0.003), distal jejunum (P = 0.004), and distal ileum (P < 0.0005). When CT-PCI was classified based on the extent of carcinomatosis, 17 cases (33%) were underestimations, of which, 11 cases (21%) were upstaged from low to moderate, 4 cases (8%) were upstaged from low to severe, and 2 cases (4%) were upstaged from moderate to severe. Relevant clinical discordance where an upstage occurred to severe carcinomatosis constituted a true inaccuracy and was observed in six cases (12%)., Conclusions: The actual clinical impact of inaccuracies of CT-PCI was modest. CT-PCI will remain as a mandatory imaging tool and may be supplemented with other tools including positron emission tomography scan or diagnostic laparoscopy, in the patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the standard of care for patients with peritoneal dissemination of appendiceal cancer and are increasingly being evaluated for use in patients with carcinomatosis from colon cancer. Mitomycin C (MMC) is one of the most frequently used HIPEC agents in the management of peritoneal-based gastrointestinal malignancies. This study analyzes the incidence and risk factors for developing neutropenia following MMC-HIPEC combined with CRS., Methods: All patients undergoing CRS and MMC-HIPEC for appendiceal cancer between January 1993 and October 2006 were retrospectively reviewed. Logistic regression was used to identify risk factors for the development of neutropenia, defined as an absolute neutrophil count (ANC) <1,000/mm(3)., Results: One hundred and twenty MMC-HIPEC were performed in 117 patients with appendiceal cancer. The incidence of neutropenia was 39%. Neutropenia occurred in 57.6% of female and 21.3% of male patients (p < 0.0001). Female gender and MMC dose per body surface area (BSA) were independent risk factors for neutropenia on multivariable logistic regression [odds ratio (OR) of neutropenia in females = 3.58 (95% confidence interval, CI: 1.52, 8.43); OR for 5 unit (mg/m(2)) increase in MMC dose per BSA = 3.37 (95% CI: 1.72, 6.63)]. Neutropenia did not increase the risk of mortality, postoperative infection or length of hospital stay., Conclusion: Neutropenia is a frequent complication associated with MMC-HIPEC. Female sex and MMC dose per BSA are independent risk factors for neutropenia. These differences must be considered in the management of patients undergoing MMC-HIPEC to minimize the toxicity of the procedure.

Aims: A new treatment strategy combining maximal cytoreductive surgery for treatment of macroscopic disease and maximal perioperative intraperitoneal chemotherapy for residual microscopic disease, suggests that in a selected group of patients benefit is possible. The purpose of this study was to report our experience with this combined treatment and to identify the principal prognostic factors., Methods: The study included 266 patients from 9 institutions operated on between July 1990 and July 2004. The median age was 55 years., Results: The mortality rate was 7.8% and the morbidity rate 37.5%. The overall median survival was 13.7 months. Positive independent prognostic factors by multivariate analysis were gender, perioperative intraperitoneal chemotherapy and treatment by the second-look procedure., Conclusions: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with an acceptable morbidity and mortality.

The initiation of a Program in Peritoneal Malignancy is a long and complex process. The novelty, technically demanding nature and steep learning curve that characterize this treatment strategy calls for a carefully planned, systematic, controlled, and informed introduction is an institution, for which an Institutional Review Board approved protocol is suggested. Commitment of a surgical team and institution, education of other physician, nurses, and ancillary personnel involved in the procedure, safety precaution for patients and health care workers, and proper patient selection are important requirements for initiating the program. This manuscript provides a guide for implementation of this treatment strategy with a minimum of untoward events, reduced apprehension of medical and nursing colleagues, and a maximum benefit for patients.

Peritoneal mesothelioma is a rare disease, but increasing in frequency. The incidence is approximately one per 1,000,000 and about one fifth to one third of all mesotheliomas are peritoneal. Because of its unusual nature, the disease has not been clearly defined either in terms of its natural history, diagnosis, or management. This article reviews a single institution's experience with 51 patients prospectively treated over the past decade with increasingly aggressive local/regional protocols. Peritoneal mesothelioma patients generally present with two types of symptoms and signs; those with abdominal pain, usually localized and related to a dominant tumor mass with little or no ascites and those without abdominal pain, but with ascites and abdominal distention. Pathologically, a positive immunostain for calretinin has markedly increased the accuracy of diagnosis. Prognosis as determined by clinical presentation, the completeness of cytoreduction, and gender (females survive longer than males) appears to be improved by the use of intraperitoneal chemotherapy. Over the past decade, the management of these patients has evolved similarly to ovarian cancer treatment and now involves cytoreductive surgery, heated intraoperative intraperitoneal chemotherapy (HIIC) with cisplatin and doxorubicin, and early postoperative intraperitoneal paclitaxel. These perioperative treatments are followed by adjuvant intraperitoneal paclitaxel and second-look cytoreduction. Prolonged disease-free survival and reduced adverse symptoms with the current management strategy are documented by a high complete response rate as assessed by a negative second-look. This multimodality treatment approach with cytoreductive surgery and intraperitoneal chemotherapy has resulted in a median survival of 50 to 60 months. Peritoneal mesothelioma is an orphan disease that is treatable with expectations for "potential" cure in a small number of patients if diagnosed and treated early with definitive local/regional treatments. A prolonged high quality of life is possible in the majority of patients., (Copyright 2002 by W.B. Saunders Company.)

Despite new developments in multi-modality treatments, complete resection remains as an absolute requirement for cure of gastrointestinal cancer. We have reported benefits from combined treatment with complete cytoreduction and intraperitoneal chemotherapy. This has been achieved with low morbidity and mortality. Success in the surgical management of peritoneal surface malignancy depends on the surgeon's ability to complete complex cytoreductive procedures so that only microscopic residual disease remains. This paper describes the current strategy that the surgical oncologist should pursue in the treatment of patients with peritoneal carcinomatosis, sarcomatosis and mesothelioma. Technical details required for this surgery include patient position, incision and exposure, complete lysis of adhesion, electroevaporative dissection with irrigation and suction to preserve the translucent quality of tissues, peritonectomy procedures, proper positioning of tubes and drains for intraperitoneal chemotherapy, and reconstructive surgery. Understanding the treatment and mastery of surgical skills to manage the peritoneal surface spread of cancer has led to long-term survival of selected patients. Combination of this treatment strategy with proper patient selection has reduced the mortality and morbidity. The success of cytoreductive surgery and perioperative intraperitoneal chemotherapy depends on a long-term dedication to achieve the full potential of a curative outcome. Our unit has continued to achieve good results over two decades as improved results of treatment have evolved., (Copyright Harcourt Publishers Limited.)