Search

Appendiceal mucinous neoplasm (AMN) is a rare tumor that may be successfully treated by appendectomy. However, some patients develop recurrence as pseudomyxoma peritonei. The present study investigated the recurrence rate after radial resection for AMN.A survey on AMN was sent to 171 institutions, and 286 cases were analyzed. The risk of recurrence was assessed according to clinical parameters. Recurrence rates were compared with data from the literature.There were 250 cases in the low-grade group and 36 in the high-grade group, with perforation being detected in 50 cases. After a median follow-up period of 30 months, recurrence was detected in 17 cases, including 12 with high-grade histology and 10 with perforation. Two patients with low-grade histology and no perforation developed recurrence. Independent prognostic factors for recurrence were high-grade histology (p = 0.0001, RR = 8.56) and perforation (p = 0.0168, RR = 3.45). Four groups were classified by histology and perforation: group A: high-grade, perforation ( +), group B: high-grade, perforation (-), group C: low-grade, perforation ( +), group D: low-grade, perforation (-). Five-year recurrence rates in groups A, B, C, and D were 46.7, 25.9, 13.3, and 1.5%, respectively. All cases of recurrence were detected within 3 years, except for two in group B.Recurrence in cases with low-grade histology and no perforation was rare; however, a postoperative survey for at least 3 years is required. In contrast, cases with high-grade histology or perforation need to be monitored using a similar approach to colon cancer. Prophylactic CRS + HIPEC may be considered.

Introduction: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. Materials and methods: CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. Results: The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. Conclusion: The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated. (c) 2021 Published by Elsevier Ltd.

Background: Cancer of the Meckel’s diverticulum (MD) is extremely rare. It is often advanced at the time of operation and the prognosis is poor. An effective treatment for this cancer has not yet been developed and there is no MD-carcinoma mouse model. Materials and Methods: MD carcinoma was established as a patient-derived xenograft (PDX) in 5-week-old male nude mice by subcutaneous transplantation of surgical specimens together with surrounding normal tissue. Hematoxylin and eosin (H&E) staining was performed on paraffin-embedded tissue sections of the original tumor resected from patients and transplanted tumors grown in nude mice. Results: Three of five mice implanted with MD tumor fragments grew. MD-carcinoma histopathology, observed with H&E-stained tissue sections of the tumors grown in the mice and tumor from the original patient, was concordant. Both showed the luminal structures characteristic of MD carcinoma, and the lumens were filled with serous fluid. Conclusion: The first PDX mouse model of MD carcinoma has been established. The PDX model maintained MD-carcinoma histology of the tumor in the patient. The MD carcinoma mouse model will enable basic research on MD carcinoma, as well as the testing of novel therapeutic agents.

Epithelial Ovarian Carcinoma (EOC), a type of cancer that is usually diagnosed in advanced stages. To date, standard treatment of EOC is surgery with neoadjuvant or adjuvant platin and taxane based systemic chemotherapy. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is considered in cases of recurrence of EOC. HIPEC has been accepted as a gold standart for the treatment of pseudomyoxoma peritonei of ovarian and appendiceal origin. More recently, a randomized clinical trial supports that HIPEC is a promising treatment option for peritoneal metastasis (PM) of ovarian cancer (OC) in surgical series. HIPEC is also reported to be an effective treatment option in primary and recurrent cancer cases with PM of OC. As a result, the standardization and optimization of the HIPEC technique, determination of patient subgroups with PM of the OC responding to treatments, personalized evaluation and the treatments currently carried out by the multidisciplinary team still need to be re-evaluated. In this review, it is aimed to update the standard treatment approach in case of peritoneal metastasis of ovarian cancer, along with the systemic treatments and HIPEC treatment approaches combined with surgery.

Peritoneal metastasis (PM) of gastric cancer (GC) is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyse a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics.We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven PM of GC, treated with CRS and HIPEC, and overall survival5 years. Patient, tumour, and therapeutic details were collected and analysed.From an analysis of 448 patients treated between 1994 and 2014, a total of 28 patients with a mean age of 53.0 years and mean PCI of 3.3 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and PCI6 were present in 22/28 patients. 12/28 patients developed at a median of 9.6 years tumour recurrence, and was associated with inferior median overall survival compared to patients without recurrence (8.8 years vs. not reached; p = 0.002).Long-term survival and even cure are possible in patients with PM of GC treated with CRS and HIPEC. Completeness of cytoreduction and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.

Peritoneal mesothelioma (PM) is a rare and aggressive primary peritoneal malignancy characterized by widespread multiple metastatic tumour nodules originating from the peritoneum. The conventional classification distinguishes diffuse malignant peritoneal mesothelioma (DMPM) and border-line forms: multicystic peritoneal mesothelioma (MCPM) and well-differentiated papillary peritoneal mesothelioma (WDPPM). Despite the novel achievements in the management of PM, there is difficulty in conducting randomized trials due to its rarity and aggressive biology in many cases. As there is, a necessity to standardize diagnosis and management of PM, the Peritoneal Surface Oncology Group International (PSOGI) commissioned a steering committee to elaborate clinical guidelines.

The treatment of patients with peritoneal metastasis from gastric cancer continues to evolve. With various forms of intraperitoneal drug delivery available, it is now possible to reach the sites of peritoneal metastases, which were otherwise sub-optimally covered by systemic chemotherapy, owing to the blood peritoneal barrier. We conducted a narrative review based on an extensive literature research, highlighting the current available intraperitoneal treatment options, which resulted in improved survival in well-selected patients of peritoneally metastasized gastric cancer. Intraperitoneal chemotherapy showed promising results in four different treatment modalities: prophylactic, neoadjuvant, adjuvant, and palliative. It is now possible to choose the type of intraperitoneal treatment/s in combination with systemic treatment/s, depending on patients’ general condition and peritoneal disease burden, thus providing individualized treatment to these patients. Randomized controlled trials for the different treatment modalities were mainly conducted in Asia and lack further validation in the other parts of the world. Most recent application tools, such as pressurized intraperitoneal aerosol chemotherapy, seem promising and need to pass the ongoing clinical trials.

Background Colorectal cancer (CRC) treatment in patients with peritoneal metastases is complex. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are under debate. The aim of this study was to assess the consensus among international experts for decision-making regarding CRS/HIPEC in CRC patients. Materials and methods Twelve of 15 experts provided their decision algorithms for CRS/HIPEC for patients with or at high risk for peritoneal metastases from CRC. Based on the objective consensus methodology, the results were transformed into decision trees, which then provided information on the consensus and discordance. Results There was only one scenario in which the consensus on performing HIPEC reached 100%, which was when treating young patients with complete cytoreduction and a peritoneal carcinomatosis index (PCI) of less than 16 in the presence of certain risk factors (RFs). Five major decision criteria were identified and displayed: age, PCI, completeness of cytoreduction (CC), extent of extraperitoneal metastases (EoM) and, in the case of nonverified extraperitoneal metastases, further RFs. There was consensus to refrain from using HIPEC in older patients with a high PCI, and the consensus further increased when addressing incomplete cytoreduction and extensive EoM. Conclusion A definite consensus concerning the use of HIPEC was only determined for very selected scenarios. These findings can be used for general guidance, but due to the heterogeneity of each individual situation and the impracticality to present this information through decision trees, as well as the unclear future of the role of HIPEC in the adjuvant setting, a one-on-one transfer to daily clinical practice cannot be achieved.

Pseudomyxoma peritonei (PMP) refers to accumulation of mucinous ascites with or without neoplastic cells in the peritoneal cavity. It most commonly originates from a low or a high grade primary appendiceal mucinous neoplasm. Though adenocarcinoma of gall bladder has been reported to give rise to PMP, to the best of our knowledge, this is the first report of a PMP arising from a low grade mucinous tumour of the gall bladder. A 72-year-old patient was diagnosed with PMP 1.5 years after a cholecystectomy. After initial oral TS1 (combination of tegafur, gimeracil and oteracil) and later intraperitoneal (IP) chemotherapy with docetaxel and cisplatin, the patient was operated with the goal of tumour debulking, including removal of 5.5 L of mucinous ascites, an appendectomy, and ovariectomy. The histopathologic report showed a normal appendix and metastasis of PMP to the right ovary. After the exclusion of the 2 most common sites of origin (appendix and ovary), the specimen of the cholecystectomy was reviewed. It showed low grade mucinous tumour in the gall bladder, with immuno-histochemical markers (IHCs) suggestive of CK7, CDX2, MUC 2 positive and CK20, MUC5AC negative. MIB-1 index was 12%. The pathologic report of cytoreductive surgery performed after 7 cycles of IP chemotherapy confirmed the diagnosis of PMP originating from low grade mucinous tumour of the gall bladder. Our case report illustrates a rare disease and highlights that, though peritoneal metastasis from gall bladder cancers are known to have a poor prognosis, the peritoneal dissemination from a low grade mucinous neoplasm of gall bladder (PMP) has a significantly better prognosis due to a better disease biology and improved treatment options currently available for the treatment of PMP.

A new treatment strategy involving cytoreductive surgery (CRS) combined with perioperative intraperitoneal (IP) chemotherapy was proposed in 1999 by the Peritoneal Surface Oncology Group International, and the strategy is now justified as a state-of-the-art treatment to improve the long-term survival of patients with peritoneal metastasis (PM). To achieve cure in the patients with PM, complete removal of macroscopic tumors and eradication of micrometastasis on the peritoneum, left after CRS are essential. Systemic chemotherapy is not indicated for the treatment of PM. In contrast, intraperitoneal (IP) chemotherapy brings about significantly higher locoregional dose intensity in the peritoneal cavity and subperitoneal tissues. In combination with anticancer drugs, hyperthermia enhances cytotoxicity against cancer cells.This article provides a systematic overview of PM from various cancers including gastric, colorectal, small bowel, appendiceal cancer, and mesothelioma. It also includes all the essential aspects of therapy.CRS plus perioperative intraperitoneal chemotherapy is safe with acceptable morbidity and mortality. It is justified as a standard treatment to improve the long-term survival of patients with PM and is now performed with curative intent for PM from various malignancies.

Highlights • Multicystic Peritoneal mesothelioma is a distinct type of peritoneal mesothelioma with borderline malignant potential and tendency to recur after tumor debulking. • Morphologically MCPM has grapelike cysts filled with clear fluid and microscopically it has cystic spaces lined by cuboidal epithelium. • There are areas of increased proliferative activity in the background of benign cyst representing potential for aggressiveness. • Peritoneal free floating cysts can be formed from disintegration of main mass and deposit in other areas to form metastatic deposits. • Comprehensive treatment – Complete cytoreduction, involved peritonectomy and HIPEC is required for treatment of macroscopic tumor and microscopic residue., Background Multicystic Peritoneal mesothelioma is a rare and distinct variety of peritoneal mesothelioma with borderline malignant potential. Conventional Tumor bulking has been associated with recurrence of 45–50 %. Hence a comprehensive treatment with Complete cytoreductive surgery with involved field peritonectomy (CRS) and Hyperthermic Intra-peritoneal chemotherapy (HIPEC) is being increasingly adopted for MCPM. Case presentation A 47 year old lady evaluated for peri-menopausal disturbance was diagnosed to have a multicystic lesion in the pelvis. With a preoperative suspicion of diagnosis of pseudomyxoma peritonei, CRS with HIPEC was planned. On exploration a diffuse multicystic mass was found in omentum and pouch of douglas with typical morphological features of MCPM. Complete cytoreduction was achieved with anterolateral and sub-diaphragmatic peritonectomy, omentectomy and panhystrectomy. HIPEC was performed with cisplatin 50 mg/m2 for 40 min. Pathological examination revealed MCPM of omentum and uterine surface with focal clusters of mesothelial proliferation. However there was low proliferative activity 1–2 %. Discussion MCPM presents with wide spread peritoneal spread but with relative sparing of visceral invasion. Literature review suggests the disease spread is similar to PMP and treatment with CCRS and HIPEC has yielded long term survivals in MCPM. Conclusions This patient with voluminous disease burden in abdomen required surgical management and HIPEC for her condition. Whether CCRS alone without HIPEC can be an alternative for limited disease will be interesting research for future clinical reports.

Highlights • Completeness of cytoreduction is the key factor for long term survival in pseudomyxoma peritonei. • Neoadjuvant chemotherapy for unresectable cases of PMP has been tried but often with discouraging results. • Intraperitoneal administration of chemotherapy can result in higher drug concentrations in the peritoneal cavity. • A seventy two year old lady presented with extensive bulky PMP received laparoscopy, Extensive Intraperitoneal lavage and Intraperitoneal chemoport insertion. • After 12 sessions of NIPT, she had complete resolution of disease and was treated with complete cytoreductive surgery with peritonectomies and Hyperthermic Intraperitoneal chemotherapy with oxaliplatin and 5-Fluorouracil. Pathologic examination showed only mucin and no atypical or neoplastic cells., Background Pseudomyxoma Peritonei (PMP) is clinical syndrome characterized by mucinous ascites and gelatinous tumor deposits in the peritoneal cavity. Complete Cytoreduction and Hyperthermic intraperitoneal perfusion is the contemporary standard of care for PMP. A novel treatment approach with Intraperitoneal (IP) chemotherapy has been developed for patients with disease not amenable for complete cytoreduction. Case presentation A 72 year old lady had PMP arising from high grade appendicular neoplasm with extensive intraabdominal spread not suitable for complete cytoreduction (PCI -19; multiple mesenteric deposits). Novel approach with tumor debulking and Neoadjuvant Intraperitoneal chemotherapy was done. Excellent clinical response was obtained after 12 sessions of IP chemotherapy with cisplatin and docetaxel. Subsequently she underwent Complete cytoreductive surgery with peritonectomy and Hyperthermic intraperitoneal chemotherapy. Pathological examination of surgical specimens revealed only acellular mucin with no viable tumor cells indicating a complete response. Discussion Complete pathological response after IP chemotherapy in extensive PMP is rare. Nevertheless the results are encouraging as the systemic therapy hasn't yielded successful outcomes. IP chemotherapy has the advantage of achieving high intraperitoneal concentrations and down staging the tumor spread. Conclusion Neoadjuvant Intra-peritoneal chemotherapy is a promising neoadjuvant strategy in patients who are poor candidates for upfront resection due to extent of disease or performance status, perhaps better than systemic therapy.

The surgical peritoneal cancer index (sPCI) is calculated based on a subjective evaluation of the extent of peritoneal disease during surgery. The pathologic PCI (pPCI) may be a more accurate and objective method for determining the PCI. This study aimed to compare the sPCI and pPCI and to study the potential pitfalls and clinical implications of using the pPCI. This prospective study (July to December 2018) included all patients undergoing cytoreductive surgery (CRS). The pPCI was calculated for each patient and compared with the sPCI. The impact of potential confounding factors on the difference between pPCI and sPCI was evaluated. Among 191 patients undergoing CRS at four centers, the pPCI and sPCI were concordant for 37 patients (19.3%). The pPCI was lower than the sPCI for 125 patients (65.4%) and higher for 29 patients (15.1%). The concordance between the two groups was maximum for gastric cancer (38.8%) and colorectal cancer (27.6%) and least for mesothelioma (6.7%) and rare primary tumors (5.6%) (p = 0.04). The difference was 0 to 3 points for 119 patients (62.3%), 4 to 5 points for 27 patients (14.1%), and more than 5 points for 45 patients (23.5%). The rate of concordance was not influenced by the use of neoadjuvant chemotherapy (NACT) (p = 0.4), but the difference was greater when NACT was used (p = 0.03). The pPCI strongly differs from the sPCI for patients undergoing CRS for peritoneal disease and may provide a more accurate evaluation of the peritoneal disease extent. Further studies are needed to determine its prognostic value compared with sPCI, and consensus guidelines are needed for calculating it.

IntroductionDespite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors.Methods and analysisThere is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied.Ethics and disseminationThe study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128).Trial registration numberCTRI/2020/09/027709; Pre-results.

BACKGROUND Pseudomyxoma peritonei (PMP) is a rare condition characterized by intraperitoneal accumulation of mucus due to mucinous neoplasia. The characteristic cytological feature of PMP in the ascites is abundant mucus with or without epithelial cell clusters. However, the prognostic significance of the presence of epithelial cell clusters has not been determined. This study aimed to determine the prognostic significance of epithelial cell clusters in the ascites of patients with PMP. METHODS Patients who were clinically and histopathologically diagnosed with PMP and who underwent intraoperative cytological examination of their ascites were included in this study. Cytological characteristics including mucus and epithelial cell clusters, nuclear atypia, and the presence of signet ring cells were investigated. Overall survival was compared based on the presence of epithelial cell clusters or nuclear atypia. RESULTS A total of 283 patients (199 women and 84 men) were investigated. The most common original site was the appendix (244 patients). Ninety patients (31.8%) had mucus without epithelial cell clusters (acellular mucin) while 193 (68.2%) had mucus with such clusters; 134 (69.4%) and 44 (22.8%) of these patients showed low-grade and high-grade nuclear features, respectively. Signet ring cells were detected in 15 patients (7.8%). The presence of epithelial cell clusters did not influence overall survival (P = .28); however, high-grade nuclear features and signet ring cell presence were significant negative prognostic factors (P < .001). CONCLUSION The presence of high-grade nuclear features or of signet ring cells should be carefully investigated in the cytological specimens of patients with PMP.

Can hyperthermic intraperitoneal chemotherapy effectively control gastric cancer-associated peritoneal carcinomatosis?

Despite advances in early diagnosis and treatment, cancer still remains the major reason of mortality worldwide. The forkhead box A (FOXA) family is reported to participate in diverse human diseases. However, little is known about their expression and prognostic values in human lung cancer. Herein, we conducted a detailed cancer vs. normal analysis. The mRNA expression levels of FOXA family in numerous kind of cancers, including lung cancer, were analyzed using the Oncomine and GEPIA database. We observed that the mRNA expression levels of FOXA1, and FOXA3 were all increased while FOXA2 were decreased in most cancers compared with normal tissues, especially in lung cancer. Moreover, the expression levels of FOXA1, and FOXA3 are also highly expressed, while FOXA2 were decreased in almost all cancer cell lines, particularly in lung cancer cell lines, analyzing by Cancer Cell Line Encyclopedia (CCLE) and EMBL-EBI databases. Furthermore, the LinkedOmics database was used to evaluate the prognostic values, indicating that higher expression of FOXA1, FOXA3 indicated a poor overall survival (OS), while increased FOXA2 revealed a better OS in lung cancer. To conclusion, FOXA family showed significant expression differences between cancer and normal tissues, especially lung cancer, and FOXA1, FOXA3 could be promising prognostic biomarkers for lung cancer.

Hsin-Hsien Yu,1,2 Yutaka Yonemura,3,4 Mao-Chih Hsieh,2,5 Chang-Yun Lu,2 Szu-Yuan Wu,6,7 Yan-Shen Shan1,8 1Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Peritoneal Dissemination Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan; 4Department of Surgery, Kusatsu General Hospital, Kusatsu, Shiga, Japan; 5Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 7Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan Objectives: The prognosis of ovarian teratoma with malignant transformation and peritoneal dissemination (PD) is poor. This condition is rare but associated with a high recurrence rate even after aggressive debulking surgery and adjuvant chemotherapy. In the present paper, we describe our experience of using cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for this condition. Methods: The data of ten female patients having ovarian teratoma with malignant transformation and PD between June 2007 and June 2017 were collected and reviewed retrospectively. CRS-HIPEC was performed according to the standard protocol. Patient characteristics, pathological reports, tumor markers, perioperative operative parameters, postoperative events, and disease status during the follow-up period were recorded. Results: The primary ovarian neoplasms were pure mature cystic teratoma with malignant transformation (n=6, including 5 of mucinous adenocarcinoma), mixed germ cell tumor with mature cystic teratoma and yolk sac tumor (YST) (n=1), pure immature teratoma (n=1), immature teratoma with growing teratoma syndrome (GTS) (n=1), and immature teratoma mixed YST with GTS (n=1). The mean levels of tumor markers, including carcinoembryonic antigen, cancer antigen 19-9 (CA19-9), and CA125, were markedly elevated. The recurrence rate was 10%. The median and mean disease-free survival (DFS) after CRS-HIPEC were 22.3 and 36.2 months, respectively, and the 5-year DFS rate is 88%. Conclusion: CRS-HIPEC is a safe therapeutic option for reducing the recurrence rate in selected patients with PD originating from ovarian teratoma with malignant transformation. Keywords: ovarian teratoma, malignant transformation, peritoneal dissemination, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy

Highlights • IPMN is not a common disease, has low risk to develop invasive lesion. But when invasion occurred, the prognosis is poor. • Malignant IPMN with peritoneal dissemination also has poor prognosis. • CRS and HIPEC can prolong survival in malignant IPMN with peritoneal dissemination patient. • Pseudomyxoma peritonei can be found as rare manifestation of IPMN, that can associate with tumor rupture form diagnostic procedure like EUS-FNA or surgical procedure., Introduction Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are treatment to deal with peritoneal dissemination that has excellent result for various cancer especially pseudomyxoma peritonei (PMP), mesothelioma. For now, this combination of treatment is still running for pancreatic adenocarcinoma but no description for pancreatic cystic tumor like malignant Intraductal papillary mucinous neoplasm (IPMN). Presentation of cases We report 3 cases of malignant IPMN with peritoneal dissemination that treated with CRS and HIPEC. Two cases have atypical presentation of malignant IPMN with PMP. HIPEC was performed using cisplatin-based regimen. The longest survival in this study is 93 months, compared to the median survival of 44.3 months without HIPEC. Discussion CRS and HIPEC have not proven to treat in patient with pancreatic cystic tumor with peritoneal dissemination. But these treatments can be improved survival outcome in selected patient. Conclusion CRS and HIPEC trend to improve survival. More studies need, not only to evaluate the role of HIPEC on malignant IPMN, but also prognosis and outcome.

Simple Summary Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy improves survival in selected patients with peritoneal metastases from colorectal cancer (CRC). However, the characteristics of long-term survivors are not well documented. This study set out to investigate the patient characteristics associated with the long-term survival of peritoneal metastases from CRC. We retrospectively analyzed 206 long-term survivors who underwent CRS for peritoneal metastases from CRC. We found that most long-term survivors showed low peritoneal cancer index (PCI), low PCI of small bowel subsets, and complete cytoreduction (CC-0), while some exhibited characteristics considered associated with poor prognosis. Abstract Background: We conducted this study to review the patient characteristics associated with long-term survival in patients with peritoneal metastases from colorectal cancer who underwent cytoreductive surgery (CRS). Methods: We retrospectively investigated patients with peritoneal metastases from CRC treated with curative intent surgery with or without hyperthermic intraperitoneal chemotherapy at 13 institutions worldwide between January 1985 and April 2015 and survived longer than five years after the first CRS for peritoneal metastases. Clinical and oncological features and therapeutic parameters were described and analyzed. Results: Two hundred six long-term survivors were available for study. The median peritoneal cancer index (PCI) of this cohort was 4 (interquartile range (IQR), 2–7), and the median score of the small bowel regions of the PCI (SB-PCI) was 0 (IQR, 0–2). Complete cytoreduction (CC-0) was achieved in 180 (87.4%) patients. Recurrence was observed in 122 (59.2%) patients at a median of 1.8 (IQR, 1.2–2.6) years. Conclusions: While most long-term survivors showed low PCI/SB-PCI and CCR-0, some had characteristics considered associated with poor prognosis. Curative intent treatments may be considered in well-informed and fit patients showing negative factors affecting survival outcome.

IntroductionDespite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery(CRS) for peritoneal metastases (PM). Apart from the peritoneal cancer index(PCI), completeness of cytoreduction and tumor grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy(SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilization of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilization of these factors in clinical decision making and the extent of peritoneal resection performed for different tumors. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors. Methods and analysisThere is no therapeutic intervention in the study. All patients with biopsy proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a pre-specified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumor nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centers will be studied. Ethics and disseminationThe study protocol has been approved by the Zydus Hospital ethics committee (27th July, 2020) and Lyon-sud ethics committee (A15-128). It is registered with the clinical trials registry of India (CTRI/2020/09/027709).The results will be published in peer-reviewed scientific journals.Strength and limitationsA prospective correlation between the radiological, surgical and pathological findings in patients undergoing CRS will be performed which has not been done before.Being prospective in nature it will also enable us to evaluate the impact of the current treatment practices on the clinical end-pointsThere is fixed protocol for radiological and pathological evaluation for which there are no specific guidelinesThe data collection format will capture all the relevant data but this may affect compliance.Despite the large sample size planned for each primary site, the heterogeneity of treatment protocols may be a limiting factor while evaluating the impact on survival.

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%-100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future.

BackgroundCytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in selected patients with peritoneal metastasis (PM) from colorectal cancer (CRC). However, little has been reported on characteristics and clinical course of long-term survivors with CRC-PM beyond 5 years. The objective of this study was to identify the clinical and oncological features affecting long-term survival of CRC-PM after comprehensive treatment.MethodsBetween January 1990 and April 2015, CRC-PM patients who underwent CRS with or without HIPEC in two Japanese tertiary hospitals were analyzed. Clinicopathological parameters and therapeutic details for long-term survivors (patients surviving ≥ 5 years after CRS) were described and compared with those for non-survivors (patients surviving ResultsThe study identified 236 patients with CRC-PM who underwent CRS, with a median follow-up period of 2.5 years. Thirty-three patients (14.0%) were considered as long-term survivors. Compared with non-survivors, long-term survivors had a lower median peritoneal cancer index (PCI) [4 (1–27) vs 9 (0–39),ppp= 0.018]. Regarding histopathology, long-term survivors more frequently had mucinous adenocarcinoma than non-survivors [8/33 (24.2%) vs 27/203 (13.3%)] and less likely exhibited poorly differentiated or signet ring cell carcinoma [2/33 (6.1%) vs 48/203 (23.7%)] (pConclusionsOne in seven patients with CRC-PM achieved the long-term milestone after CRS. A long-term survival was associated with the presence of low PCI, CCR-0, metachronous onset, and mucinous histology.

Simple Summary Approximately 1% of all patients with colorectal cancer, and 15% of patients with peritoneal metastasized colorectal cancer present with the subtype of signet ring cell, which is associated with inferior oncological outcome and reduced overall survival. The evidence whether patients with signet ring cell subtype are benefiting from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is limited. The aim of this large bicentric retrospective study including 60 patients with this subtype was to explore the survival and define predictive factors of these patients. Median overall survival was 14.4 months, while small bowel PCI > 2 (HR: 6.5; p = 0.008) was the strongest predictive factor for inferior patient survival. The study concludes, that after thoroughly selection patients for CRS and HIPEC, even patients with signet ring cell subtype of colorectal cancer may benefit from this concept. Abstract Signet ring cell subtype (SRC) of colorectal cancer (CRC) is a rare subtype and occurs in approximately 1% of all patients with CRC. Patients with peritoneal metastasis (PM) of SRC have a poor prognosis, and this subtype is frequently considered as a contra-indication for extensive surgical treatment. This retrospective study from two dedicated peritoneal surface malignancy centers in Japan included all patients treated with CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between July 1994 and December 2017 from a prospectively maintained database. Preoperative, operative, and postoperative parameters were recorded, including complication rates and follow-up. Sixty of the 320 patients treated with CRS due to CRC were diagnosed with SRC subtype. The mean age of the patients was 51.4 years, and the mean peritoneal carcinomatosis index (PCI) was 13.1. Complete cytoreduction was achieved in 61.7% of cases. The postoperative morbidity rate was 25% and the mortality rate was 1.7%. The median overall survival (OS) was 14.4 months. Cox regression analysis revealed small bowel PCI > 2 (hazard ratio (HR) 6.5; p = 0.008) as the most important factor for OS. With accurate patient selection (e.g., PCI ≤ 12 or small bowel PCI ≤ 2), even patients with PM of CRC with SRC subtype may benefit from CRS and HIPEC, with median OS from 17.8 to 20.8 months and 5-year OS of 11.6%.

Neoadjuvant intravenous chemotherapy in patients with pseudomyxoma peritonei (PMP) has not shown convincing results. The effectiveness of neoadjuvant intraperitoneal (IP) chemotherapy has never been reported. This prospective, non-randomized phase II study included patients with PMP treated between May 2017 and December 2018, who were not considered suitable for primary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The majority of patients were treated with laparoscopic HIPEC (oxaliplatin 200 mg/m2, 60 min, 43 &deg, C). IP chemotherapy was started 2 weeks after docetaxel 40 mg/m2 + cisplatin 40 mg/m2, accompanied by oral S1 (tegafur, gimeracil, and oteracil) (50 mg/m2) for 14 days, followed by one week rest. Clinical parameters and complications were recorded. In total, 22/27 patients qualified for CRS and HIPEC after neoadjuvant treatment. A complete cytoreduction (Completeness of cytoreduction Score 0/1) could be achieved in 54.5%. The postoperative morbidity rate was 13.6% and mortality was rate 4.5%. In total, 20/22 patients had major pathological tumor responses. The mean drop in CEA was 28.2% and in the peritoneal carcinomatosis index (PCI) was 2.6. Positive or suspicious cytology turned negative in 69.2% of patients. Thus, for PMP patients who were not amenable for primary surgery, the majority received complete cytoreduction after treatment with neoadjuvant IP chemotherapy, with satisfying tumor regression and with low complication rates. The oncological benefit in terms of survival with this new treatment regimen needs to be proven.

Objectives: To assess the individual treatment strategies among international experts in peritoneal carcinosis, specifically their decision-making in the process of patient selection for hyperthermic intraperitoneal chemotherapy (HIPEC) in women suffering from ovarian cancer, to identify relevant decision-making criteria, and to quantify the level of consensus for or against HIPEC. Methods: The members of the executive committee of the Peritoneal Surface Oncology Group International (PSOGI) were asked to describe the clinical conditions under which they would recommend HIPEC in patients with ovarian cancer and to describe any disease or patient characteristics relevant to their decision. All answers were then merged and converted into decision trees. The decision trees were then analyzed by applying the objective consensus methodology. Results: Nine experts in surgical oncology provided information on their multidisciplinary treatment strategy including HIPEC for patients with advanced ovarian cancer. Three of the total of 12 experts did not perform HIPEC. Five criteria relevant to the decision on whether HIPEC is performed were applied. In patients with resectable disease, a peritoneal cancer index (PCI) Discussion and Conclusion: Among surgical oncology experts in peritoneal surface malignancy and HIPEC, HIPEC plays an important role in primary and recurrent ovarian cancer, and the PCI is the most important criterion in this decision.

Peritoneal Surface Oncology Group International(PSOGI)proposed a novel treatment, named comprehensive treatment for peritoneal metastasis(PM)from colorectal cancer(CRC). The present study demonstrated the efficacies of the treatment regarding the peritoneal sectors and organs involved with PM from CRC.Among 365 patients received laparotomy, 278 CRC patients with PM underwent complete cytoreductive surgery(CC-0).After CC-0 resection Grade 3, Grade 4, and Grade 5 postoperative complication were found in 20(7.2%), 26(9.3%), and 6(2.2%). Five- and 10-year survival rate(YSR)of CC-0 resection were 24.5%, and 11.6% with median survival time(MST)of 42.0 months. Regarding the peritoneal cancer index(PCI)of small bowel(SB-PCI), all patients of PCI B3 died of the disease. In contrast, 10-YSR of patients with SB-PCI of 0, 1, and 2 were 26.1%, 19.5%, and 6.2%, respectively. Ten-YSR of patients with the number of involved peritoneal sectors C9 ranged from 6.9% to 29.8%. MST of patients with PM in each peritoneal sector(sector 0 to sector 8)ranged from 26.4 months to 49.2 months, and 10-YSR ranged from 4.2%to 17.2%. Ten-YSR of patients with involvement of rectum, stomach, liver capsule, seminal vesicle, ureter, uterus, or ovary ranged from 0% to 16.9%.From the present data, PM should be removed aggressively to achieve complete cytoreduction, when the patients with PCIC26, involved peritoneal sectorsC9 and SB-PCIC2 are supposed to receive complete cytoreduction of PM.

Mechanisms of peritoneal metastasis (PM) formation remain unclear. It has long been considered that the establishment of PM is a multi-step process. Here are the recent new concepts of the formation of PM, in terms of three patterns of PM: trans-mesothelial, trans-lymphatic, and superficial growing metastasis. Trans-mesothelial metastasis is established through detachment of cancer cells, adhesion on distant peritoneal surface, invasion into submesothelial tissue, and proliferation. Trans-lymphatic metastasis develops by the migration of peritoneal free cancer cells (PFCCs) into omental milky spots and/or initial lymphatic vessels. Superficial growing metastasis is established by growing of PFCCs on the peritoneal surface after trapping or adhesion to pocket-like structure or pouch in pelvic cavity or in peritoneum absorbed by negative pressure generated omental milky spots or initial lymphatic vessels.

Pseudomyxoma peritonei (PMP) is the intraperitoneal accumulation of mucus due to a mucinous tumor. PMP predominantly occurs in low-grade carcinomas. The incidence rate of PMP is one to two cases per million people per year. The standard therapy of PMP comprises complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PMP recurs in about 50% of patients, and 30–40% are unable to receive the standard treatment because of its invasiveness. Therefore, novel therapies are of the utmost necessity. For basic and pre-clinical research, patient-derived cell lines are essential resources. However, only two PMP cell lines have been reported. Thus, we established a novel PMP cell line from resected metastatic PMP tissue. The cell line, named NCC-PMP1-C1, was maintained for more than 5 months and was passaged 25 times. NCC-PMP1-C1 cells demonstrated multiple deletions, slow growth, tumorigenic ability, and dissemination of tumor cells in nude mice. We also used NCC-PMP1-C1 cells to screen drugs, which demonstrated a significant response to daunorubicin HCl, homoharringtonine, mitomycin C, and ponatinib. The NCC-PMP1-C1 cell line is the first PMP cell line derived from metastasized tissue and will be a potential resource for basic and pre-clinical research of metastasized PMP.

In the present article, we describe the normal structure of the peritoneum and review the mechanisms of peritoneal metastasis (PM) from gastric cancer (GC). The structure of the peritoneum was studied by a double-enzyme staining method using alkaline-phosphatase and 5′-nucreotidase, scanning electron microscopy, and immunohistological methods. The fundamental structure consists of three layers, mesothelial cells and a basement membrane (layer 1), macula cribriformis (MC) (layer 2), and submesothelial connective tissue containing blood vessels and initial lymphatic vessels, attached to holes in the MC (layer 3). Macro molecules and macrophages migrate from mesothelial stomata to the initial lymphatic vessels through holes in the MC. These structures are characteristically found in the diaphragm, omentum, paracolic gutter, pelvic peritoneum, and falciform ligament. The first step of PM is spillage of cancer cells (peritoneal free cancer cells; PFCCs) into the peritoneal cavity from the serosal surface of the primary tumor or cancer cell contamination from lymphatic and blood vessels torn during surgical procedures. After PFCCs adhere to the peritoneal surface, PMs form by three processes, i.e., (1) trans-mesothelial metastasis, (2) trans-lymphatic metastasis, and (3) superficial growing metastasis. Because the intraperitoneal (IP) dose intensity is significantly higher when generated by IP chemotherapy than by systemic chemotherapy, IP chemotherapy has a great role in the treatment of PFCCs, superficial growing metastasis, trans-lymphatic metastasis and in the early stages of trans-mesothelial metastasis. However, an established trans-mesothelial metastasis has its own interstitial tissue and vasculature which generate high interstitial pressure. Accordingly, it is reasonable to treat established trans-mesothelial metastasis by bidirectional chemotherapy from both IP and systemic chemotherapy.

This review provides an overview of articles about peritoneal mesothelioma (PM) to analyze the effect of treatment modalities on response rates, post-treatment side effects, morbidity and mortality, and survival. Median survival in months following systemic chemotherapy (SC) ranged from 8.7 to 26.8 months. However, no patient was reported to have survived for more than five years with SC alone. In contrast, comprehensive treatment that included cytoreductive surgery (CRS) + perioperative chemotherapy (POC) showed a significantly longer median survival time than SC alone. Additionally, CRS + POC demonstrated 10-year survival rates of 12%-35%. Accordingly, CRS + POC is an innovative treatment that provides long-term survival in selected patients with PM. Selection criteria are performance status (ECOG PS ≤ 1), the absence of extraperitoneal metastasis, PCI less than cutoff levels (from < 10 to < 28), MIB-1 index (< 10), and histologic type (epithelioid type). Postoperative morbidity and mortality rates after CRS + POC were significantly higher than with more conventional operations. Accordingly, CRS and POC should be done at the specialized peritoneal surface malignancy centers.

This study was conducted to verify the effects of cytoreductive surgery (CRS) combined with perioperative chemotherapy (POC), using neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), extensive intraperitoneal lavage (EIPL), and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis from gastric cancer (GC-PM). Combination of these treatments is called “comprehensive treatment.” The survival rate after comprehensive treatment was significantly superior to that after systemic chemotherapy. Complete cytoreduction and peritoneal cancer index (PCI) less than cutoff level after NIPS are independent prognostic factors. NIPS could bring stage reduction of PM and eradicate micrometastasis in the peritoneal cavity, resulting in an increase in complete cytoreduction rate of PM. At present, 10% of GC-PM can be cured by the comprehensive treatment because micrometastasis left behind after complete cytoreduction of macroscopic PM might be completely eradicated by HIPEC and postoperative chemotherapy.

The aim was to study the patterns of target region (greater omentum, lesser omentum, falciform and umbilical round ligament) involvement in patients undergoing cytoreductive surgery (CRS) from various primary tumors, factors affecting involvement and implications on surgical practice.All patients undergoing CRS from July 2018 to December 2018 were included in this prospective study. The incidence of target region involvement in presence and absence of visible disease and the impact of primary tumor site, PCI and other variables on target region involvement was evaluated.In 191 patients, greater omentum was involved in over 15% of patients irrespective of the primary tumor type and in 15.7% in absence of visible disease. 75% of these had PCI20. The involvement of the other three target regions was higher than 20% in ovarian cancer, appendiceal tumors and peritoneal mesothelioma. Involvement of these 3 regions was associated with a higher PCI (p 0.001 for all) and omental involvement (p 0.001for all). 2.1% of colorectal cancer patients had umbilical round ligament involvement, 4.2% had falciform ligament involvement and none had lesser omentum involvement.Target region involvement varies according to primary tumour site and disease extent. Resection of the greater omentum should be performed during CRS for PM arising from all primary sites. Resection of other target organs may be performed for selected patients with ovarian cancer, peritoneal mesothelioma and mucinous appendiceal tumors in absence of visible disease. For other patients, it should be done only in presence of visible disease.

Background and aim The grade/histological subtype is one of the most important prognostic markers in patients undergoing cytoreductive surgery (CRS). Our aim was to study other potential prognostic information that can be derived from the pathological evaluation of CRS specimens and provide a broad outline for evaluation of these. Methods This prospective study (July to December 2018) included all patients undergoing cytoreductive surgery (CRS). A protocol for pathological evaluation was laid down which was based on existing practices at the participating centers and included evaluation of the pathological PCI, regional node involvement, response to chemotherapy, morphology of peritoneal metastases (PM) and distribution in the peritoneal cavity. Results In 191 patients undergoing CRS at 4 centers, the pathological and surgical PCI differed in over 75%. Nodes in relation to peritoneal disease were positive in 13.6%. Disease in normal peritoneum adjacent to tumor nodules was seen in >50% patients with ovarian cancer and mucinous apppendiceal tumors. 23.8% of evaluated colorectal PM patients had a complete response and 25.0% ovarian cancer patients had a near complete pathological response to chemotherapy. Conclusions Pathological evaluation of extent and distribution of peritoneal disease differs from the surgical evaluation in majority of the patients. Lymph node involvement in relation of peritoneal disease is common. The morphological presentation of PM in ovarian cancer and mucinous appendiceal tumors merits evaluation of more extensive resections in these patients. Standardized methods of synoptic reporting of CRS specimens could help capture vital prognostic information that may in future influence how these patients are treated.

Summary Background: Neoadjuvant Intraperitoneal/ Systemic Chemotherapy (NIPS) is considered effective method to treat Peritoneal Metastasis (PM) from Gastric Cancer (GC). The objective of the present study is to verify the effect of NIPS on Lymph Node Metastasis (LNM). Methods: During the last 18 years, we enrolled 107 and 136 patients who underwent D2-gastrectomy after NIPS and D2-gastrectomy alone (non-NIPS group), respectively. Results: The total number of LNMs in the non-NIPS group and NIPS group was 14.8 ± 13.9 and 4.6 ± 5.9, respectively (P NIPS is a very effective method to control LNM from GC. After intraperitoneal administration of chemotherapeutic drug, extremely higher concentrations of chemotherapeutic drug are absorbed through omental milky spots, and the efferent lymphatic fluid drain into the regional lymph nodes of stomach. As a result, regional LNM of stomach are exposed with extremely higher concentrations of chemotherapeutic drugs than systemic chemotherapy. This feature of the lymphatic circulation accounts for the much greater effects of NIPS on LNM. Synopsis: Neoadjuvant intraperitoneal/systemic chemotherapy is effective not only peritoneal metastasis but also lymph node metastasis from gastric cancer. Keywords: Gastric cancer; Lymph node metastasis; Neoadjuvant intraperitoneal/systemic chemotherapy

Treatment failure after complete cytoreduction for appendiceal mucinous carcinoma peritonei (AMCP)has not been fully investigated. The present study was performed to clarify the risk factor for recurrence after complete cytoreduction for AMCP.A total of 400 patients with AMCP who underwent complete cytoreductive surgery combined with perioperative chemotherapy were investigated.Documented recurrence was developed in 135 (33.8%)patients. The 5- and 10-year progression-free survival was 51% and 49%, respectively. By multivariate analysis, histological subtype of peritoneal disease(high-grade AMCP[AMCP-H]and AMCP-H with signet ring cells), serum CA19- 9 level, and PCIB20 were significantly associated with reduced progression-free survival. In contrast, histologic subtype of mucin without epithelial cells(MWEC)showed the lowest risk for recurrence. Eighty-six patients had localized intra-abdominal recurrence, and 42 patients had diffuse peritoneal recurrence. Recurrence was found in the various peritoneal sectors. Eighty-one patients underwent complete cytoreduction for the recurrence, and the overall survival 5-year survival rate after secondary cytoreduction was 49%.Risk factors for recurrence were histologic subtype, PCI cutoff level, and serum CA19-9 levels. Aggressive second attempt of cytoreduction in patients with localized recurrence improved the survival.

The current standard of treatment for malignant peritoneal mesothelioma(MPM)is cytoreductive surgery(CRS)plus perioperative intraperitoneal or systemic chemotherapy(comprehensive treatment), The present study was performed to clarify the prognostic factors of PMP after comprehensive treatment.Among 63 patients with MPM, male and female patients were 34 and 29. CRSwas performed in 47 patients and complete cytoreduction(CC-0) was performed in 14(22%)patients. Mean numbers of resected peritoneal sectors and organs were 5.2(1-13), and 2.9(0- 9), respectively. Hyperthermic intraperitoneal chemoperfusion(HIPEC)was performed in 27 patients. Grade 1/2, Grade 3, and Grade 4 complications were experienced in 5, 6, and 3 patients, respectively. One patient died of sepsis, and the mortality rate was 2.3%. Independent prognostic factors for favorable prognosis were performance of HIPEC, peritoneal cancer index (PCI)score C12, no distant metastasis and histologic epithelial type. Relative risk of no HIPEC, PCI score B13, presence of distant metastasis and non epithelial type were 7.69, 22.1, 3.6 and 3.9, respectively.Risk factors for death after comprehensive treatment were no HIPEC, PCI score B13, and non epithelial type. However, only 11(17%)patients showed PCI score C12. Accordingly, PCI score should be reducedC12 before CRSby neoadjuvant chemotherapy.

International audience; Background and Objectives: The aims of this multi‐institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival.Methods: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases.Results: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high‐grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence‐free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5‐year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11‐20; P 20), high‐grade complications ( P = 0.012), and incomplete cytoreduction ( P

In this review, Japanese experience of cytoreductive surgery and perioperative chemotherapy is described. The new concept of peritoneal metastasis (PM) type, i.e., trans-mesothelial, trans-lymphatic, and superficial growing metastasis type was proposed in 2012. Surgeons should perform peritonectomy according to the type of PM. Since 1980, Japanese surgical oncologists have been spearheading the use of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemoperfusion (HIPEC) as treatment for PM from gastric cancer. Two RCTs were conducted to verify the effect of HIPEC for the prophylaxis of peritoneal recurrence after curative resection of advanced gastric cancer. These two studies indicated that HIPEC is effective in preventing peritoneal recurrence of gastric cancer with serosal invasion. In 2002, intraperitoneal chemotherapy using taxans was developed for the treatment of PM from gastric cancer and led to the development of neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), which was reported in 2006. In 2009, extensive intra-operative peritoneal lavage (EIPL) was developed, and contributed to the remarkable improvement in survival of patients with positive lavage cytology as demonstrated by prospective randomized clinical trials. In 2017, the Peritoneal Surface Oncology Group International proposed the value of complete cytoreduction and peritoneal cancer index cut-off as independent prognostic factors after CRS for gastric cancer with PM. Founded in 2016, the Japanese/Asian School of Peritoneal Surface Oncology (JASPSO) trains beginners to perform CRS and HIPEC safely. Sixteen students have already graduated from JASPSO and started to perform the treatment in their home countries.

Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available.To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP.This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018.HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens.Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models.Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P .001; E-value, 2.03). Such prognostic advantage was associated with oxaliplatin plus fluorouracil-leucovorin (HR, 0.42; 95% CI, 0.19-0.93; P = .03) and cisplatin plus mitomycin (HR, 0.57; 95% CI, 0.42-0.78; P = .001) schedules.In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.

BACKGROUND: Despite the best standard treatment, optimal cytoreductive surgery (CRS) and platinum/taxane-based chemotherapy, prognosis of advanced epithelial ovarian carcinoma (EOC) remains poor. Recently, CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed to treat peritoneal carcinomatosis (PC). This study was to evaluate the efficacy and safety of CRS+HIPEC to treat PC from advanced/recurrent EOC. METHODS: Forty-six PC patients from advanced EOC (group A) or recurrent EOC (group B) were treated by 50 CRS+HIPEC procedures. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were safety profiles. RESULTS: The median OS was 74.0 months [95% confidence interval (CI) 8.5-139.5] for group A versus 57.5 months (95% CI 29.8-85.2) for group B (P = .68). The median PFS was not reached for group A versus 8.5 months (95% CI 0-17.5) for group B (P = .034). Better median OS correlated with peritoneal cancer index (PCI) < 20 (76.6 months for PCI ≤ 20 group vs 38.5 months for PCI > 20 group, P = .01), complete cyroreduction (residual disease ≤ 2.5 mm) [79.5 months for completeness of cytoreduction (CC) score 0-1 vs 24.3 months for CC 2-3, P = .00], and sensitivity to platinum (65.3 months for platinum-sensitive group vs 20.0 for platinum-resistant group, P = .05). Serious adverse events occurred in five patients (10.0%). Multivariate analysis identified CC score as the only independent factor for better survival. CONCLUSION: For advanced/recurrent EOC, CRS+HIPEC could improve OS with acceptable safety.

To report the morbidity and risk factors for overall complications and for pancreatic fistula (PF) after distal pancreatic resection (DP) during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).The safety of DP in patients with peritoneal surface malignancies treated by CRS and HIPEC has been debated. The risk of PF and its impact on surgical outcomes are not well defined.Between 2001 and 2012, 118 patients with peritoneal surface malignancy undergoing CRS/HIPEC required DP at 7 oncological surgical centers. The incidence, clinical impact, and risk factors of PF were analyzed.The indications for DP were tumoral invasion of the pancreatic gland with (n = 24; 20%) or without splenic extension (n = 76; 64%), invasion of the pancreatic capsule (n = 10; 9%), or iatrogenic lesions during CRS (n = 8; 7%). The rate of 90 days postoperative mortality was 7.6%, and the rate of severe morbidity (Clavien-Dindo ≥III) was 44%. Pancreatic fistula was observed in 39 cases (33%), with the majority grade B (48.7%) or C (28.2%). In multivariate analysis, the risk factors for PF were a peritoneal cancer index more than 20 (risk ratio: 3.01; P = 0.022) and an operative time more than 550 min (risk ratio: 2.74; P = 0.038). The occurrence of PF was not associated with a higher risk of 90-day mortality (5.1% vs 8.8%, not significant).With regard to reported morbi-mortality rates, DP associated with CRS/HIPEC may be a reasonable procedure in highly selected patients when done in high-volume centers. Therefore, distal pancreatic involvement should not be considered as a definitive contraindication for CRS/HIPEC in patients with resectable peritoneal surface disease.

390 Background: Peritoneal metastasis of gastric cancer is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in median survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyze a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics. Methods: We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven peritoneal metastasis of gastric cancer, treated with CRS and HIPEC, and overall survival > 5 years. Patient, tumor, and therapeutic details were collected and analyzed. Results: A total of 29 patients with a mean age of 52.5 years and a mean PCI of 3.2 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and low PCI (PCI < 6) were present in 23/29 patients. 13/29 patients developed at a median of 82.2 months tumor recurrence. Tumor recurrence was associated with inferior median overall survival compared to patients without tumor recurrence (8.8 years vs. not reached; p = 0.002). Conclusions: Long-term survival and even cure are possible in patients with peritoneal metastasis of gastric cancer treated with CRS and HIPEC. Completeness of cytoreduction (CC-0) and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.