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      Repeated cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with recurrent peritoneal carcinomatosis

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          Abstract

          Background

          Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the treatment of choice for resectable peritoneal carcinomatosis (PC) and improved the survival of these patients. The situation changes if PC recurs and repeated CRS with HIPEC is considered. The patient selection and outcome of the repeated approach has not been well described. We analyzed our cohort and share the experiences.

          Methods

          Ninety-three CRS/HIPEC procedures, performed in 85 patients during the period 2001–2013, were examined in a retrospective analysis. Type of primary, ECOG status, peritoneal cancer index (PCI), completeness of cytoreduction (CC), duration of hospitalization, postoperative morbidity, mortality, and disease-free/overall survival were reviewed.

          Results

          Six patients (7 %) underwent a second CRS/HIPEC (median interval between the two procedures: 26 months, range 8–61) including two patients with mesotheliomas, one patient with ovarian adenocarcinoma, one patient with leiomyosarcoma of uterus, one patient with colon adenocarcinoma, and one patient with appendiceal adenocarcinoma. The last two patients underwent a third CRS/HIPEC, 25 and 36 months, after the second procedure. The median PCI was 14 (range, 4–26) during the first and 20 (range, 7–39) during the second CRS/HIPEC of these patients. Completeness of cytoreduction score of 0 (CC-0) was achieved in all first procedures and in 67 % of second procedures (CC-0; n = 4 and CC-1; n = 2). A CC-0 score was possible in both of the third procedures. The mean operating time was 444 min (range, 198–642) and 427 min (range, 239–617) during the first and the second procedure. Median intensive care unit (ICU) was 2 days, and hospital stay after second CRS/HIPEC was 17 days (range, 7–50). The 30-day morbidity after repeated CRS/HIPEC was 33 % (16 % for grade III–IV complications), and there was no 30-day mortality neither after the second nor after the third CRS/HIPEC. Median disease-free interval between first CRS/HIPEC and peritoneal recurrence was 17 months (range, 8–30). Median disease-free survival of 18 months (range, 4–33) was achieved after the second CRS/HIPEC. After a median follow-up of 74 months (range, 39–151), all patients are alive with disease ( n = 5) or disease free ( n = 1) under chemotherapy.

          Conclusions

          In experienced centers, repeated CRS/HIPEC can be performed with safety. Patient selection and correct timing is of particular importance in achieving control of the disease. Repeated CRS/HIPEC should be considered as treatment option for selected patients with recurrent PC.

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          Most cited references44

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          Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study.

          PURPOSE Peritoneal carcinomatosis (PC) from colorectal cancer traditionally is considered a terminal condition. Approaches that combine cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with that strategy. PATIENTS AND METHODS A retrospective-cohort, multicentric study from French-speaking countries was performed. All consecutive patients with PC from colorectal cancer who were treated with CRS and PIC (with or without hyperthermia) were included. Patients with PC of appendiceal origin were excluded. Results The study included 523 patients from 23 centers in four French-speaking countries who underwent operation between 1990 and 2007. The median follow-up was 45 months. Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, and five-year disease-free survival was 10%. Complete CRS was performed in 84% of the patients, and median survival was 33 months. Positive independent prognostic factors identified in the multivariate analysis were complete CRS, PC that was limited in extent, no invaded lymph nodes, and the use of adjuvant chemotherapy. Neither the grade of disease nor the presence of liver metastases had a significant prognostic impact. CONCLUSION This combined treatment approach against PC achieved low postoperative morbidity and mortality, and it provided good long-term survival in patients with peritoneal scores lower than 20. These results should improve in the future, because the different teams involved will gain experience. This approach, when feasible, is now considered the gold standard in the French guidelines.
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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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              Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.

              The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.
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                Author and article information

                Contributors
                +49-9131-85-33296 , nikolaos.vassos@uk-erlangen.de
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central (London )
                1477-7819
                24 February 2016
                24 February 2016
                2016
                : 14
                : 42
                Affiliations
                [ ]Department of Surgery, University Hospital Erlangen, Krankenhausstrasse 12, 91054 Erlangen, Germany
                [ ]National Cancer Center of Georgia, Tbilisi, Georgia
                Article
                804
                10.1186/s12957-016-0804-x
                4765140
                26912149
                b5a7a81f-5dd6-494d-a214-a009d4175f70
                © Vassos et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 September 2015
                : 17 February 2016
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Surgery
                cytoreductive surgery,crs,repeated,iterative procedure,hipec,peritoneal surface malignancy,recurrent peritoneal carcinomatosis

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