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      Retrospective Analysis of Patients with Signet Ring Subtype of Colorectal Cancer with Peritoneal Metastasis Treated with CRS & HIPEC

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          Abstract

          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%.

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          Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.

          Although quality assessment is gaining increasing attention, there is still no consensus on how to define and grade postoperative complications. This shortcoming hampers comparison of outcome data among different centers and therapies and over time. A classification of complications published by one of the authors in 1992 was critically re-evaluated and modified to increase its accuracy and its acceptability in the surgical community. Modifications mainly focused on the manner of reporting life-threatening and permanently disabling complications. The new grading system still mostly relies on the therapy used to treat the complication. The classification was tested in a cohort of 6336 patients who underwent elective general surgery at our institution. The reproducibility and personal judgment of the classification were evaluated through an international survey with 2 questionnaires sent to 10 surgical centers worldwide. The new ranking system significantly correlated with complexity of surgery (P < 0.0001) as well as with the length of the hospital stay (P < 0.0001). A total of 144 surgeons from 10 different centers around the world and at different levels of training returned the survey. Ninety percent of the case presentations were correctly graded. The classification was considered to be simple (92% of the respondents), reproducible (91%), logical (92%), useful (90%), and comprehensive (89%). The answers of both questionnaires were not dependent on the origin of the reply and the level of training of the surgeons. The new complication classification appears reliable and may represent a compelling tool for quality assessment in surgery in all parts of the world.
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            Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin.

            To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated. The standard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time. Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospectively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P < .05, log-rank test). Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.
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              Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer.

              To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin. Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) with or without palliative surgery, or experimental therapy consisting of aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regime. The primary end point was survival. After a median follow-up period of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm (log-rank test, P =.032). The treatment-related mortality in the aggressive therapy group was 8%. Most complications from HIPEC were related to bowel leakage. Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions (log-rank test, P <.0001). If the cytoreduction was macroscopically complete (R-1), the median survival was also significantly better than in patients with limited (R-2a), or extensive residual disease (R-2b; log-rank test, P <.0001). Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin. However, patients with involvement of six or more regions of the abdominal cavity, or grossly incomplete cytoreduction, had still a grave prognosis.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                07 September 2020
                September 2020
                : 12
                : 9
                : 2536
                Affiliations
                [1 ]Department of Surgical Oncology, Thangam Cancer Center, Namakkal 637001, Tamil Nadu, India; dranuprabhu.surgeon@ 123456gmail.com
                [2 ]Digestive Unit, Champalimaud Foundation, 1400-038 Lisbon, Portugal; andreas.brandl@ 123456fundacaochampalimaud.pt
                [3 ]Department of surgery, Graduate school of medicine, Kyoto University, Kyoto 606-8303, Japan; wakama9@ 123456kuhp.kyoto-u.ac.jp
                [4 ]Department of Regional Cancer therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka 596-0042, Japan; sako-rgb.009@ 123456cap.ocn.ne.jp (S.S.); haruaki.ishibashi@ 123456tokushukai.jp (H.I.); yang.liu@ 123456tokushukai.jp (Y.L.)
                [5 ]NPO to Support Peritoneal Surface Malignancy Treatment, Japanese/Asian School of Peritoneal Surface Oncology, Kyoto 600-8189, Japan
                [6 ]Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga 525-8585, Japan; mizumoto@ 123456kusatsu-gh.or.jp (A.M.); takao@ 123456kusatsu-gh.or.jp (N.T.); noguchi@ 123456kusatsu-gh.or.jp (K.N.); motoi@ 123456kusatsu-gh.or.jp (S.M.); ichinose@ 123456kusatsu-gh.or.jp (M.I.)
                Author notes
                [* ]Correspondence: y.yonemura@ 123456coda.ocn.ne.jp ; Tel.: +81-724459915; Fax: +81-72-445-9791
                Author information
                https://orcid.org/0000-0003-1990-2584
                Article
                cancers-12-02536
                10.3390/cancers12092536
                7565458
                32906609
                18d944d8-9a14-4c7a-aab9-4cc57ca06d3e
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 04 July 2020
                : 26 August 2020
                Categories
                Article

                colorectal cancer,signet ring sub-type,peritoneal metastasis,cytoreductive surgery,hyperthermic intraperitoneal chemotherapy

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