Journal of Surgical Oncology 2014;110:970–975
Higher Flow Rates Improve Heating During Hyperthermic Intraperitoneal Chemoperfusion MATTHEW J. FURMAN, MD,1 ROBERT J. PICOTTE, CCP,2 MARK J. WANTE, CCP,2 BARUR R. RAJESHKUMAR, PhD,1 GILES F. WHALEN, MD,1 AND LAURA A. LAMBERT, MD1* 1
Division of Surgical Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts 2 Department of Surgery, University of Massachusetts Medical Center, Worcester, Massachusetts
Background/Objectives: Heated intraperitoneal chemotherapy (HIPEC) kills cancer cells via thermal injury and improved chemotherapeutic cytotoxicity. We hypothesize that higher HIPEC flow rates improve peritoneal heating and HIPEC efficacy. Methods: (1) A HIPEC‐model (30.8 L cooler with attached extracorporeal pump) was filled with 37°C water containing a suspended 1 L saline bag (SB) wrapped in a cooling sleeve, creating a constant heat sink. (2) HIPECs were performed in a swine model. Inflow, outflow, and peritoneal temperatures were monitored as flow rates varied. (3) Flow rates and temperatures during 20 HIPECs were reviewed. Results: Higher flow rates decreased time required to increase water bath (WB) and SB temperature to 43°C. With a constant heat sink, the minimum flow rate required to reach 43°C in the WB was 1.75 L/min. Higher flow rates lead to greater temperature gradients between the WB and SB. In the swine model, the minimum flow rate required to reach 43°C outflow was 2.5–3.0 L/min. Higher flows led to more rapid heating of the peritoneum and greater peritoneal/outflow temperature gradients. Increased flow during clinical HIPEC suggested improved peritoneal heating with lower average visceral temperatures. Conclusions: There is a minimum flow rate required to reach goal temperature during HIPEC. Flow rate is an important variable in achieving and maintaining goal temperatures during HIPEC.
J. Surg. Oncol. 2014;110:970–975. ß 2014 Wiley Periodicals, Inc.
KEY WORDS: heated intraperitoneal chemotherapy; flow rates; chemosensitivity; heat sink
INTRODUCTION Hyperthermic intraperitoneal chemoperfusion (HIPEC) in combination with aggressive cytoreductive surgery (CRS) is used with increasing frequency for treatment of isolated, resectable peritoneal carcinomatosis. The rationale for the combined treatment approach of CRS and HIPEC is to expose the peritoneal cavity to supra‐therapeutic doses of hyperthermic chemotherapy at the time of maximal cytoreduction and minimal tumor burden. HIPEC is technically accomplished by circulating 3–6 L of hyperthermic chemotherapy through the peritoneal cavity at the time of CRS. Specialized equipment, which both heats and circulates the chemotherapy during the perfusion is required to reach temperatures of 40–43°C in the peritoneal cavity during HIPEC. Because the cytotoxicity of hyperthermia is temperature and time dependent, an important aspect of HIPEC is the ability to efficiently reach and maintain the goal temperature within the peritoneal cavity [1–3]. One option to more quickly reach and maintain goal temperature is to increase the inflow temperature of the perfusate. However, this option is limited by the risk of toxicity to the patient. Another option is to change the rate of flow of the HIPEC. To date, no studies have investigated the impact of flow rate on the heating of the peritoneal cavity during the perfusion. In this study, we hypothesized that increasing the rate of flow during HIPEC would improve heating of the peritoneal cavity. This study presents data from an in vitro model, a swine model and clinical data demonstrating that (i) increasing the rate of flow during HIPEC leads to more rapid heating of the peritoneal cavity, and (ii) there is a minimum rate of flow required to reach and maintain the goal peritoneal temperature.
METHODS An in vitro HIPEC model was created using a 30.8 L capacity cooler attached to a Bio‐Console 560 Medtronic extracorporeal pump. (Fig. 1A
ß 2014 Wiley Periodicals, Inc.
and C) The cooler was filled with 26 L of 37°C water containing a suspended, submerged, 1 L saline bag (SB) (Fig. 1B). A temperature probe was placed within the water bath (WB) and another sealed within the SB. Prior to initiating any perfusions, WB and SB temperatures were stabilized at 37°C. The perfusate was heated to 43°C and infused through the model at 1–4 L/min. These in vitro experiments were run identically at least three separate times to confirm the reliability of the model. The temperatures of both the WB and SB were monitored and recorded at 1 min intervals. Using the same model, a separate set of experiments, performed in triplicate, were executed using a topical cooling device (Terumo) repurposed from a cardiac cooling pump. The cooling sleeve was wrapped around the SB (Fig. 1B). Cooled water was run through the sleeve to keep the internal SB temperature at 37°C, thereby creating a heat sink within the model. 43°C water was circulated through the model at rates between 1 and 4 L/min. The temperatures of both the WB and SB were monitored and recorded at 1 min intervals. With IACUC (Institutional Animal Care and Use Committee) approval, two HIPEC procedures, using an identical extracorporeal pump set‐up as described above, were performed on Yorkshire Swine (weight 60–65 kg). Under general anesthesia, a celiotomy was performed through a midline incision. Three temperature probes were secured within the liver and upper and lower peritoneum. Core
*Correspondence to: Laura A. Lambert, M.D., Division of Surgical Oncology, UMass Memorial Medical Center, 119 Belmont St, Swift House, Worcester, MA 01605. Fax: 508‐334‐5089 E‐mail: [email protected] Received 24 March 2014; Accepted 3 August 2014 DOI 10.1002/jso.23776 Published online 29 August 2014 in Wiley Online Library (wileyonlinelibrary.com).
Higher Flow Rates Improve HIPEC Heating
971
pelvis and brought out through the inferior portion of the midline incision. The abdomen was closed in a watertight fashion at the level of the skin with a running suture. The perfusate (0.9% sodium chloride) was heated to 43°C prior to beginning the perfusion. The first perfusion began at a flow rate of 4 L/min. Inflow temperature, outflow temperature, and the intraperitoneal site temperatures were continuously monitored and recorded at 15 min intervals. After reaching 43°C on the peritoneal temperature probes, the flow was incrementally decreased by 0.5 L/min every 15 min to a rate of 0.5 L/min. The perfusion in the second animal began at a rate of 0.5 L/min. After reaching a constant temperature for 30 min, the flow rate was incrementally increased by 0.5 L/min every 15 min to 4 L/min. Inflow temperature, outflow temperature, and the intraperitoneal site temperatures were continuously monitored and recorded at 15 min intervals. All experiments, in vitro and in vivo, utilized the same heat exchanger, thereby removing the efficacy of the heat exchanger from the variability of the results. A retrospective review of prospectively collected data from all HIPECs done at our institution between March and December of 2011 was performed. Flow rates, inflow, outflow, bladder, and esophageal temperatures from the procedures were recorded at 15 min intervals. The data were analyzed to determine a relationship between HIPEC flow rates and intraperitoneal temperatures. Statistical analysis was performed using SAS 9.2 statistical software. Groups were compared using either the chi‐squared test or t test as indicated. A P value of
Higher Flow Rates Improve Heating During Hyperthermic Intraperitoneal Chemoperfusion MATTHEW J. FURMAN, MD,1 ROBERT J. PICOTTE, CCP,2 MARK J. WANTE, CCP,2 BARUR R. RAJESHKUMAR, PhD,1 GILES F. WHALEN, MD,1 AND LAURA A. LAMBERT, MD1* 1
Division of Surgical Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts 2 Department of Surgery, University of Massachusetts Medical Center, Worcester, Massachusetts
Background/Objectives: Heated intraperitoneal chemotherapy (HIPEC) kills cancer cells via thermal injury and improved chemotherapeutic cytotoxicity. We hypothesize that higher HIPEC flow rates improve peritoneal heating and HIPEC efficacy. Methods: (1) A HIPEC‐model (30.8 L cooler with attached extracorporeal pump) was filled with 37°C water containing a suspended 1 L saline bag (SB) wrapped in a cooling sleeve, creating a constant heat sink. (2) HIPECs were performed in a swine model. Inflow, outflow, and peritoneal temperatures were monitored as flow rates varied. (3) Flow rates and temperatures during 20 HIPECs were reviewed. Results: Higher flow rates decreased time required to increase water bath (WB) and SB temperature to 43°C. With a constant heat sink, the minimum flow rate required to reach 43°C in the WB was 1.75 L/min. Higher flow rates lead to greater temperature gradients between the WB and SB. In the swine model, the minimum flow rate required to reach 43°C outflow was 2.5–3.0 L/min. Higher flows led to more rapid heating of the peritoneum and greater peritoneal/outflow temperature gradients. Increased flow during clinical HIPEC suggested improved peritoneal heating with lower average visceral temperatures. Conclusions: There is a minimum flow rate required to reach goal temperature during HIPEC. Flow rate is an important variable in achieving and maintaining goal temperatures during HIPEC.
J. Surg. Oncol. 2014;110:970–975. ß 2014 Wiley Periodicals, Inc.
KEY WORDS: heated intraperitoneal chemotherapy; flow rates; chemosensitivity; heat sink
INTRODUCTION Hyperthermic intraperitoneal chemoperfusion (HIPEC) in combination with aggressive cytoreductive surgery (CRS) is used with increasing frequency for treatment of isolated, resectable peritoneal carcinomatosis. The rationale for the combined treatment approach of CRS and HIPEC is to expose the peritoneal cavity to supra‐therapeutic doses of hyperthermic chemotherapy at the time of maximal cytoreduction and minimal tumor burden. HIPEC is technically accomplished by circulating 3–6 L of hyperthermic chemotherapy through the peritoneal cavity at the time of CRS. Specialized equipment, which both heats and circulates the chemotherapy during the perfusion is required to reach temperatures of 40–43°C in the peritoneal cavity during HIPEC. Because the cytotoxicity of hyperthermia is temperature and time dependent, an important aspect of HIPEC is the ability to efficiently reach and maintain the goal temperature within the peritoneal cavity [1–3]. One option to more quickly reach and maintain goal temperature is to increase the inflow temperature of the perfusate. However, this option is limited by the risk of toxicity to the patient. Another option is to change the rate of flow of the HIPEC. To date, no studies have investigated the impact of flow rate on the heating of the peritoneal cavity during the perfusion. In this study, we hypothesized that increasing the rate of flow during HIPEC would improve heating of the peritoneal cavity. This study presents data from an in vitro model, a swine model and clinical data demonstrating that (i) increasing the rate of flow during HIPEC leads to more rapid heating of the peritoneal cavity, and (ii) there is a minimum rate of flow required to reach and maintain the goal peritoneal temperature.
METHODS An in vitro HIPEC model was created using a 30.8 L capacity cooler attached to a Bio‐Console 560 Medtronic extracorporeal pump. (Fig. 1A
ß 2014 Wiley Periodicals, Inc.
and C) The cooler was filled with 26 L of 37°C water containing a suspended, submerged, 1 L saline bag (SB) (Fig. 1B). A temperature probe was placed within the water bath (WB) and another sealed within the SB. Prior to initiating any perfusions, WB and SB temperatures were stabilized at 37°C. The perfusate was heated to 43°C and infused through the model at 1–4 L/min. These in vitro experiments were run identically at least three separate times to confirm the reliability of the model. The temperatures of both the WB and SB were monitored and recorded at 1 min intervals. Using the same model, a separate set of experiments, performed in triplicate, were executed using a topical cooling device (Terumo) repurposed from a cardiac cooling pump. The cooling sleeve was wrapped around the SB (Fig. 1B). Cooled water was run through the sleeve to keep the internal SB temperature at 37°C, thereby creating a heat sink within the model. 43°C water was circulated through the model at rates between 1 and 4 L/min. The temperatures of both the WB and SB were monitored and recorded at 1 min intervals. With IACUC (Institutional Animal Care and Use Committee) approval, two HIPEC procedures, using an identical extracorporeal pump set‐up as described above, were performed on Yorkshire Swine (weight 60–65 kg). Under general anesthesia, a celiotomy was performed through a midline incision. Three temperature probes were secured within the liver and upper and lower peritoneum. Core
*Correspondence to: Laura A. Lambert, M.D., Division of Surgical Oncology, UMass Memorial Medical Center, 119 Belmont St, Swift House, Worcester, MA 01605. Fax: 508‐334‐5089 E‐mail: [email protected] Received 24 March 2014; Accepted 3 August 2014 DOI 10.1002/jso.23776 Published online 29 August 2014 in Wiley Online Library (wileyonlinelibrary.com).
Higher Flow Rates Improve HIPEC Heating
971
pelvis and brought out through the inferior portion of the midline incision. The abdomen was closed in a watertight fashion at the level of the skin with a running suture. The perfusate (0.9% sodium chloride) was heated to 43°C prior to beginning the perfusion. The first perfusion began at a flow rate of 4 L/min. Inflow temperature, outflow temperature, and the intraperitoneal site temperatures were continuously monitored and recorded at 15 min intervals. After reaching 43°C on the peritoneal temperature probes, the flow was incrementally decreased by 0.5 L/min every 15 min to a rate of 0.5 L/min. The perfusion in the second animal began at a rate of 0.5 L/min. After reaching a constant temperature for 30 min, the flow rate was incrementally increased by 0.5 L/min every 15 min to 4 L/min. Inflow temperature, outflow temperature, and the intraperitoneal site temperatures were continuously monitored and recorded at 15 min intervals. All experiments, in vitro and in vivo, utilized the same heat exchanger, thereby removing the efficacy of the heat exchanger from the variability of the results. A retrospective review of prospectively collected data from all HIPECs done at our institution between March and December of 2011 was performed. Flow rates, inflow, outflow, bladder, and esophageal temperatures from the procedures were recorded at 15 min intervals. The data were analyzed to determine a relationship between HIPEC flow rates and intraperitoneal temperatures. Statistical analysis was performed using SAS 9.2 statistical software. Groups were compared using either the chi‐squared test or t test as indicated. A P value of
![[Morbidity and mortality of hyperthermic intraperitoneal chemoperfusion].](/assets/img/hold.png)
