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      Are there intra-operative hemodynamic differences between the Coliseum and closed HIPEC techniques in the treatment of peritoneal metastasis? A retrospective cohort study

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          Abstract

          Background

          Although two main methods of intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) are currently accepted, the superiority of one over the other has not yet been demonstrated. The purpose of this study was to determine whether there are hemodynamic and temperature differences between patients who received HIPEC in two different techniques, open versus closed abdomen.

          Methods

          This retrospective study was conducted in our center between 2011–2015 in 30 patients who underwent surgery for peritoneal carcinomatosis secondary to colorectal cancer, in whom cytoreduction and HIPEC were performed by the Coliseum (15) or closed techniques (15). The main end points were morbidity, mortality, hemodynamic changes, and abdominal temperature. The comparative analysis of quantitative variables at different times was done with the parametric repeated measure ANOVA for those variables that fulfilled the suppositions of normality and independence and the Friedman non-parametric test for the variables that did not fulfill either of these suppositions.

          Results

          There were no deaths in either group. The incidence of postoperative complications in the Coliseum group was 53% (8 patients), grade II–III. The incidence of complications in the closed group was 13% (2 patients), grade II–III. The intra-operative conditions regarding the systolic and diastolic pressures were more stable using the closed abdomen technique (but not significantly so). We found statistically significant differences in abdominal temperature in favor of the closed technique ( p = 0.009).

          Conclusions

          Both HIPEC procedures are similar. In our series, the closed technique resulted in a more stable intra-abdominal temperature.

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          Most cited references15

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          Hyperthermic intraperitoneal chemotherapy: Rationale and technique.

          The combination of complete cytoreductive surgery and perioperative intraperitoneal chemotherapy provides the only chance for long-term survival for selected patients diagnosed with a variety of peritoneal neoplasms, either primary or secondary to digestive or gynecologic malignancy. Hyperthermic intraperitoneal chemotherapy (HIPEC) delivered in the operating room once the cytoreductive surgical procedure is finalized, constitutes the most common form of administration of perioperative intraperitoneal chemotherapy. This may be complemented in some instances with early postoperative intraperitoneal chemotherapy (EPIC). HIPEC combines the pharmacokinetic advantage inherent to the intracavitary delivery of certain cytotoxic drugs, which results in regional dose intensification, with the direct cytotoxic effect of hyperthermia. Hyperthermia exhibits a selective cell-killing effect in malignant cells by itself, potentiates the cytotoxic effect of certain chemotherapy agents and enhances the tissue penetration of the administered drug. The chemotherapeutic agents employed in HIPEC need to have a cell cycle nonspecific mechanism of action and should ideally show a heat-synergistic cytotoxic effect. Delivery of HIPEC requires an apparatus that heats and circulates the chemotherapeutic solution so that a stable temperature is maintained in the peritoneal cavity during the procedure. An open abdomen (Coliseum) or closed abdomen technique may be used, with no significant differences in efficacy proven to date. Specific technical training and a solid knowledge of regional chemotherapy management are required. Concerns about safety of the procedure for operating room personnel are expected but are manageable if universal precautions and standard chemotherapy handling procedures are used. Different HIPEC drug regimens and dosages are currently in use. A tendency for concurrent intravenous chemotherapy administration (bidirectional chemotherapy, so-called "HIPEC plus") has been observed in recent years, with the aim to further enhance the cytotoxic potential of HIPEC. Future trials to ascertain the ideal HIPEC regimen in different diseases and to evaluate the efficacy of new drugs or drug combinations in this context are warranted.
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            Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution.

            This article reports the pharmacokinetics (PK) of heated intra-operative intraperitoneal oxaliplatin and its tolerance profile. Oxaliplatin has demonstrated significant activity in advanced colorectal cancer, and this is the first publication concerning its intraperitoneal administration. Twenty consecutive patients with peritoneal carcinomatosis (PC) of either gastrointestinal or uniquely peritoneal origin underwent complete cytoreductive surgery followed by intra-operative intraperitoneal chemo-hyperthermia (IPCH) with increasing doses of oxaliplatin. We performed IPCH using an open procedure (skin pulled upwards), at an intraperitoneal temperature of 42-44 degrees C, with 2 l/m2 of 5% dextrose instillate in a closed circuit. The flow-rate was 2 l/min for 30 min. Patients received intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2) just before the IPCH to maximize the effect of oxaliplatin. We treated at least three patients at each of the six intraperitoneal oxaliplatin dose levels (from 260 to 460 mg/m2) before progressing to the next. We analysed intraperitoneal, plasma and tissue samples with atomic absorption spectrophotometry. The mean duration of the entire procedure was 8.4 +/- 2.7 h. Half the oxaliplatin dose was absorbed in 30 min at all dose levels. Area under the curve (AUC) and maximal plasma concentration (Cmax) increased with dose. At the highest dose level (460 mg/m2), peritoneal oxaliplatin concentration was 25-fold that in plasma. AUCs following intraperitoneal administration were consistently inferior to historical control AUCs after intravenous oxaliplatin (130 mg/m2). Intratumoral oxaliplatin penetration was high, similar to absorption at the peritoneal surface and 17.8-fold higher than that in non-bathed tissues. Increasing instillate volume to 2.5 l/m2 instead of 2 l/m2 dramatically decreased oxaliplatin concentration and absorption. There were no deaths, nor severe haematological, renal or neurological toxicity, but we observed two fistulas and three deep abscesses. Heated intraperitoneal chemotherapy gives high peritoneal and tumour oxaliplatin concentrations with limited systemic absorption. We recommend an oxaliplatin dose of 460 mg/m2 in 2 l/m2 of 5% dextrose for intraperitoneal chemo-hyperthermia, at a temperature of 42-44 degrees C over 30 min. We may be able to improve these results by increasing the intraperitoneal perfusion duration or by modifying the instillate composition.
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              Peri-operative anaesthetic management of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

              Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is a long and complex procedure with significant blood and fluid loss during debulking and important pathophysiological alterations during the HIPEC phase. We performed a retrospective analysis of 78 consecutive patients undergoing cytoreductive surgery with HIPEC at a university hospital. Our data demonstrate large intra-operative fluid turnover, with 51% of patients requiring a blood transfusion. During HIPEC, airway pressure and central venous pressure increased with a lower oxygenation ratio as a result of increased intra-abdominal pressure with the closed abdomen technique. As a consequence of the raised body temperature, heart rate, end tidal carbon dioxide and arterial lactate levels increased with a slight metabolic acidosis. Peri-operative analysis of routine clotting parameters revealed disturbances of the coagulation status. For pain management, 72% of patients received supplementary thoracic epidural analgesia with consequential peri-operative opioid sparing and a reduced duration of postoperative ventilation.
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                Author and article information

                Contributors
                cristinars86@gmail.com
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central (London )
                1477-7819
                21 February 2017
                21 February 2017
                2017
                : 15
                : 51
                Affiliations
                GRID grid.411457.2, Universidad de Málaga, Departamento de Farmacología, , Servicio de Cirugía General, Digestiva y Trasplantes, Hospital Regional Universitario de Málaga, ; Avda Carlos Haya, 29020 Malaga, Spain
                Author information
                http://orcid.org/0000-0002-1084-2223
                Article
                1119
                10.1186/s12957-017-1119-2
                5320712
                28222738
                64e6b5bc-fe6c-4ebc-9680-1be5c7db6ec0
                © The Author(s). 2017

                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
                : 19 December 2016
                : 8 February 2017
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Surgery
                peritoneal carcinomatosis,coliseum technique,closed technique,hipec,peritoneal metastasis
                Surgery
                peritoneal carcinomatosis, coliseum technique, closed technique, hipec, peritoneal metastasis

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