Continuous Hyperthermic Peritoneal Perfusion Research Articles

Association of serum levels of deoxyribose 1-phosphate and S-lactoylglutathione with neoadjuvant chemotherapy sensitivity in patients with gastric cancer: A metabolomics study.

The present study screened serum samples from patients with advanced-stage gastric cancer and known sensitivities to neoadjuvant chemotherapy, in order to identify metabolites that may serve as potential biomarkers for chemotherapy sensitivity. A total of 47 patients with stage III (T4b) or IV gastric cancer, including 31 in the training group and 16 in a validation group, were classified based on their responses to conversion therapy consisting of oxaliplatin, tegafur and continuous hyperthermic peritoneal perfusion with cisplatin. Serum samples were analyzed by liquid chromatography-mass spectrometry to obtain a metabolite profile of each patient. Patients who were responsive and non-responsive to neoadjuvant chemotherapy exhibited significant differences in serum levels of deoxyribose 1-phosphate, S-lactoylglutathione, lysophosphatidylcholine (16:0) and O-arachidonoyl ethanolamine. Logistic regression analysis indicated that deoxyribose 1-phosphate and S-lactoylglutathione were independently associated with chemosensitivity. Serum levels of deoxyribose 1-phosphate and S-lactoylglutathione were independently associated with the sensitivity of gastric cancer to neoadjuvant chemotherapy, therefore, serving as potential predictors of patient response.

Comparison of the therapeutic effects of continuous hyperthermic peritoneal perfusion with systemic intravenous chemotherapy

Purpose: To compare the effectiveness and safety of intravenous cisplatin (DDP) and 5-fluorouracil (5-FU) alone or in combination with continuous hyperthermic peritoneal perfusion (CHPP) for the treatment of malignant ascites.Methods: In the study, 124 patients with tumour-induced malignant ascites were assign to test and control groups according to the sequence of their hospital visits. Patients in the test group were treated with intravenous DDP and 5-FU combined with CHPP, whereas patients in the control group were only treated with DDP and 5-FU. The treatments in both groups lasted for 4 weeks. Thereafter, treatment efficacy, remission of abdominal distension, ascites, Karnofsky Performance Scale (KPS) score, and incidence of adverse reactions were compared between the two groups.Results: The overall response rates of the test and control groups were 85.50 (53/62) and 35.50 % (22/62), respectively, and the difference was significant (p < 0.05). Patients in the test group showed significant reduction in abdominal distension and markedly reduced ascites compared to the controls. The improvement in KPS score was superior in the test group (p < 0.05). No treatment-associated complications, such as intestinal adhesions or obstruction and grade III or IV toxic and side reactions, were found in either group. The incidence of adverse reactions was lower in the test group than in the controls.Conclusion: Chemotherapy in combination with CHPP is safe and effective for patients with advanced malignant tumours and ascites should be promoted clinically.Keywords: Malignant ascites, Continuous hyperthermic peritoneal perfusion, Systemic intravenous chemotherapy

Efficacy of continuous hyperthermic peritoneal perfusion chemotherapy for malignant seroperitoneum

Efficacy of continuous hyperthermic peritoneal perfusion chemotherapy for malignant seroperitoneum

Desmoplastic small round cell tumor: review of therapy including surgery followed by continuous hyperthermic peritoneal perfusion of chemotherapy

Desmoplastic small round cell tumor: review of therapy including surgery followed by continuous hyperthermic peritoneal perfusion of chemotherapy

Desmoplastic small round cell tumor: review of therapy including surgery followed by continuous hyperthermic peritoneal perfusion of chemotherapy

Desmoplastic small round cell tumor (DSRCT) is a very rare disease of children, adolescents, and young adults and involves the abdominal cavity. DSRCT has characteristic fusion gene involving EWS1 and WT1 translocation, t(11;22)(p13;q12). Unlike Ewing’s sarcoma of bone, DSRCT usually presents with diffuse peritoneal implants that are prone to recur. The primary organ of origin of DSRCT is mesenchyme of the peritoneum. This makes it a very unique tumor that is difficult to treat because of the infiltrative and diffuse nature of the peritoneum. The challenge of local control is to remove dozens to hundreds of tumors studding the peritoneal cavity, and then eliminate microscopic disease. We review a sequential multimodality strategy to reduce macroscopic and microscopic disease including neoadjuvant chemotherapy, aggressive surgery including an emerging new therapy to use after surgery to treat microscopic residual disease: continuous hyperthermic peritoneal chemotherapy,

Care of Pediatric Oncology Patients After Continuous Hyperthermic Peritoneal Perfusion

Care of Pediatric Oncology Patients After Continuous Hyperthermic Peritoneal Perfusion

A phase I trial of continuous hyperthermic peritoneal perfusion using cisplatin in pediatric patients with carcinomatosis.

9544 Background: The delivery of regional hyperthermic chemotherapy using continuous hyperthermic peritoneal perfusion (CHPP) has been well established in adults with carcinomatosis. This approach has not previously been used in children. Here we report a phase I trial of CHPP using cisplatin after extensive cytoreductive surgery for pediatric patients with extensive abdominal metastasis from sarcomatosis or mesothelioma. Methods: This phase I study includes 10 enrollments in patients age 3 to 18 years who received dose escalation of cisplatin after cytoreductive surgery followed by CHPP at a single institution. A standard 3 by 3 dose escalation format was used starting at 100 mg/m2. Patients diagnosed with desmoplastic small round cell tumor (DSRCT), rhabdomyosarcoma (RMS), liposarcoma and mesothelioma who had refractory and extensive abdominal disease were included. Patients with liver metastasis were included. However, patients with disease outside of the abdominal cavity were excluded. A summary of morbidities and toxicities including dose limiting toxicity (DLT) and maximum tolerated dose (MTD) are reported. Results: All subjects enrolled completed the study and there were no on study mortalities. DLT was renal insufficiency manifest as elevation in creatinine without the need for dialysis. MTD was 150 mg/m2 given for 90 minutes at 40.5 degrees Celsius. There were 2 grade 3 renal toxicities, 2 grade 3 hematologic toxicities, 2 grade 3 hepatic toxicities and one grade 3 ileus. There was one grade 3 cardiomyopathy, asymptomatic and resolved with Beta blockers and one grade 4 wound complication. Number of tumor implants removed prior to hyperthermic perfusion with cisplatin ranged from 5 to 402 including splenectomy, partial diaphragm resection, bowel resection, cholecystectomy and partial peritonectomy. Hospital stay ranged from 5 to 13 days. Forty percent of patients had progressive disease (PD) and 60% had a complete response (CR) for at least 6 months. Conclusions: CHPP using cisplatin is safe in children at a dose of 100 mg/m2 at 40.5 degrees Celsius for 90 minutes. Renal insufficiency is likely at doses at, or greater than150 mg/m2. No significant financial relationships to disclose.

Desmoplastic small round cell tumor: review of therapy including surgery followed by continuous hyperthermic peritoneal perfusion of chemotherapy

Desmoplastic small round cell tumor (DSRCT) is a very rare disease of children, adolescents, and young adults and involves the abdominal cavity. DSRCT has characteristic fusion gene involving EWS1 and WT1 translocation, t(11;22)(p13;q12). Unlike Ewing’s sarcoma of bone, DSRCT usually presents with diffuse peritoneal implants that are prone to recur. The primary organ of origin of DSRCT is mesenchyme of the peritoneum. This makes it a very unique tumor that is difficult to treat because of the infiltrative and diffuse nature of the peritoneum. The challenge of local control is to remove dozens to hundreds of tumors studding the peritoneal cavity, and then eliminate microscopic disease. We review a sequential multimodality strategy to reduce macroscopic and microscopic disease including neoadjuvant chemotherapy, aggressive surgery including an emerging new therapy to use after surgery to treat microscopic residual disease: continuous hyperthermic peritoneal chemotherapy, then radiation and adjuvant chemotherapy.

Cytoreductive Surgery and Continuous Hyperthermic Peritoneal Perfusion in Patients with Mesothelioma and Peritoneal Carcinomatosis: Hemodynamic, Metabolic, and Anesthetic Considerations

Cytoreductive surgery and continuous hyperthermic peritoneal perfusion (CHPP) involve the conduct of a complex surgical procedure and delivery of high-dose hyperthermic chemotherapy to the peritoneum. This therapeutic modality has been shown to benefit patients with peritoneal carcinomatosis resulting from gastrointestinal and ovarian tumors and mesothelioma. However, it is unknown whether the primary disease (mesothelioma versus peritoneal carcinomatosis) affects hemodynamic and metabolic perturbations during the course of CHPP with cisplatin. We examined the perioperative course of patients undergoing CHPP with cisplatin and evaluated the effect of primary diagnosis (mesothelioma versus peritoneal carcinomatosis) on hemodynamic and metabolic parameters in response to peritoneal perfusion. Sixty-nine mesothelioma and 100 peritoneal carcinomatosis patients underwent 169 consecutive cytoreduction and CHPP procedures with general anesthesia. During CHPP, patients from both groups developed significant increases in central venous pressure, and heart rate, decreases in mean arterial pressure (all P < 0.0001), metabolic acidosis with significant decreases in pH and bicarbonate (P < 0.0001), deterioration of gas exchange with significant increases in PaCO(2) and oxygen alveolar-arterial gradient (P < 0.0001), and significant increases in activated partial thromboplastin time (aPTT) and prothrombin time (PT) and decreases in hematocrit and platelet counts (all P < 0.0001). However, patients with mesothelioma had lesser increases in temperature (P < 0.01) and heart rate (P < 0.0001) and lesser decreases in hematocrit (P = 0.0013) during CHPP and greater decreases in sodium bicarbonate (P = 0.0082) after completion of CHPP compared with patients with peritoneal carcinomatosis. We conclude that the transient hemodynamic and metabolic perturbations associated with cytoreductive surgery and CHPP with cisplatin can vary according to the primary diagnosis (mesothelioma versus peritoneal carcinomatosis) warranting this therapy.

Efficacy of early continuous hyperthermic peritoneal perfusion on patients with advanced gastric carcinoma after surgical resection

To evaluate the efficacy of early continuous hyperthermic peritoneal perfusion (CHPP) on patients of advanced gastric carcinoma after surgical resection. Seventy patients were divided into control and treatment group. Patients in treatment group received CHPP 1 or 2 days postoperatively. Treatment was administered daily consecutively for 4 days. Patients in control group underwent resection of gastric carcinoma without CHPP. Chemotherapy was administered of Calcium Folinate and 5-Fluorouracil (LF regimen) intravenously for 6 cycles in both groups two or three weeks postoperatively. Survival and recurrence in both groups were observed and compared. One-year survival and recurrence rates were 83.3% and 8.3% in treatment group, 79.4% and 11.7% in control group, there were no significant differences between the two groups. Three-year survival and recurrence rates were 63.9% and 19.4 in treatment group, 39.8% and 44.1% in control group, there were significant differences between the two groups. Early administration of CHPP to patients with advanced gastric carcinoma after surgery may be advantageous for preventing peritoneal metastasis and recurrence, thus may prolong survival time.

Continuous hyperthermic peritoneal perfusion for desmoplastic small round cell tumor

Desmoplastic small round cell tumor (DSRCT) is a rare disease of children, adolescents, and young adults that begins and spreads on the peritoneal surfaces. Desmoplastic small round cell tumor usually presents with diffuse abdominal metastatic disease similar in gross appearance to carcinomatosis. To date, very aggressive treatment programs have yielded dismal outcomes. Here we present 2 cases of DSRCT that were treated with aggressive surgical excision followed by intraoperative continuous hyperthermic peritoneal perfusion using cisplatin. These are the first pediatric case reports of DSRCT being treated with continuous hyperthermic peritoneal perfusion, a procedure usually used in treatment of adult carcinomatosis.

Novel therapeutic approaches in pediatric and young adult sarcomas

Novel therapy as part of sarcoma treatment schemas can enhance quality of life and is important in improving outcomes of high-risk sarcomas. Additional chemotherapy and biotherapy options to reduce tumor burden and prevent metastases include intra-arterial chemotherapy in osteosarcoma; intrapleural chemotherapy, aerosol 9-nitrocamptothecin, or protracted irinotecan and temozolomide in Ewing's sarcoma; continuous hyperthermic peritoneal perfusion for malignancy involving the peritoneum, such as desmoplastic small round cell tumor; and ifosfamide with muramyl tripeptide phosphatidyl ethanolamine liposomes in osteosarcoma. These treatments bring improved control of symptoms, including reduction in nausea, mucositis, cardiotoxicity, and central nervous system toxicity. Portable infusion devices have facilitated introduction of outpatient doxorubicin, ifosfamide, and methotrexate regimens and home-infusion irinotecan. Physical approaches to eliminate sarcoma tumors and metastases are critical for durable responses. Novel local control measures include embolization before surgery, radiosensitization, anti-vascular endothelial growth factor therapy during chemo-radiotherapy, proton therapy, samarium, thermal ablation (radiofrequency ablation), and cryoablation.

The “Alphabet Soup” of Peritoneal Dissemination From Appendiceal Neoplasms and Other Malignancies

Appendiceal neoplasms are a rare clinical entity that typify the real estate adage: location is everything. Similar to the pathophysiology of appendicitis, increasing intraluminal pressure from tumor obstruction or mucin production leads to appendiceal rupture with subsequent peritoneal dissemination (PD). By definition, this is considered stage IV disease for gastrointestinal cancers because of the poor prognosis associated with the clinical inability to control tumor progression. But does PD require the same inherent biological aggressiveness as lymphatic or hematogenous spread? The answer to this question is ‘‘not always.’’ For example, accidental spillage of an appendiceal adenoma will lead to PD despite a negligible risk for hematogenous metastases. This may also be true for an early-stage colorectal cancer. In this issue of the Annals, there are two articles—one by Stewart et al. and one by Sugarbaker et al.—regarding studies that used cytoreductive surgery (CS) and regional peritoneal therapy for PD from appendiceal neoplasms; they illustrate the evolution of a focused regional approach for, primarily, a locoregional problem. As previously noted by other authors, the treatment of PD from appendiceal neoplasms serves as an excellent example of Dr. Blake Cady s philosophy: ‘‘In the field of surgical oncology, tumor biology is king, patient selection is queen, and technical maneuvers are the prince and princess who try, but usually fail, to usurp the throne.’’ Historically, PD from appendiceal neoplasms has been categorized as either a nonmucinous high-grade tumor (similar to colorectal cancer) or as pseudomyxoma peritonei (PMP). Clinically, PMP presents as abundant intra-abdominal mucin secondary to disseminated tumor. Systemic chemotherapy has rarely been effective for this disease as a result of the overall slow growth of PMP in general, the ability of microscopic cells to survive in the peritoneal cavity by diffusion alone (i.e., no established blood supply), and limited drug penetration secondary to the plasma/peritoneal barrier. The majority of appendiceal PMP patients succumb to intra-abdominal complications (obstruction or perforation), malnutrition, or a declining performance status secondary to progressive, symptomatic mucin/tumor. Consequently, palliative surgical debulking initially evolved as the primary treatment modality to maintain a patent, functional gastrointestinal tract. Even after complete debulking of gross disease, microscopic tumor is present that invariably leads to recurrence. Attempts to eradicate this residual subclinical disease have led to the development of regional therapy approaches such as CS with intraperitoneal hyperthermic chemoperfusion (IPHC), also known as hyperthermic intraperitoneal chemotherapy, hyperthermic intraoperative intraperitoneal chemotherapy, continuous hyperthermic peritoneal perfusion chemotherapy, intraperitoneal hyperthermic perfusion, or hyperthermic antiblastic peritoneal perfusion. Biologically, PMP is actually a spectrum of aggressiveness ranging from diffuse peritoneal adenomucinosis (DPAM) to peritoneal mucinous carcinomatosis (PMC or PMCA), with PMCA and intermediate/discordant features in the middle. In the Received January 5, 2006; accepted January 5, 2006; published online March 16, 2006. Address correspondence and reprint requests to: John M. Kane III, MD; E-mail: john.kane@roswellpark.org.

Limited Survival in Patients With Carcinomatosis From Foregut Malignancies After Cytoreduction and Continuous Hyperthermic Peritoneal Perfusion

Peritoneal carcinomatosis is a frequent mode of metastasis in patients with gastric, duodenal, or pancreatic cancer. Survival in this setting is short and therapeutic options are limited. This analysis examines the outcomes of 18 patients treated with operative cytoreduction and continuous hyperthermic peritoneal perfusion. Eighteen patients (6 males and 12 females) with gastric (n = 9), pancreatic (n = 7), or duodenal (n = 2) cancer were treated on protocol. Patients underwent optimal cytoreduction (complete gross resection, 11; minimal residual disease, 7) and a 90-minute perfusion with cisplatin. Clinical parameters and tumor and treatment characteristics were analyzed. Survival curves were estimated using the Kaplan-Meier method. Procedures included gastrectomy (n = 8), pancreaticoduodenectomy (n = 3), and hemicolectomy (n = 2). After cytoreduction, patients had no evidence of residual disease (n = 11), fewer than 100 implants less than 5 mm (n = 1), more than 100 implants between 5-10 mm (n = 3), or multiple implants with greater than 1 cm (n = 3). Five patients received a postoperative intraperitoneal dwell with 5-fluorouracil and paclitaxel. There was one perioperative mortality, and complications occurred in 10 patients. The median progression-free survival was 8 months (mean, 10 months; range, 1-47 months) with a median overall survival of 8 months (mean, 18 months; range, 1-74 months). In this cohort, peritoneal perfusion with cisplatin used to treat foregut malignancies has a high incidence of complications and does not significantly alter the natural history of the disease. Investigation of novel therapeutic approaches should be considered.

Les péritonites encapsulantes

Sclerosing peritonitis (also described as sclerosing obstructive peritonitis, encapsulating peritonitis, obliterative adhesive peritonitis, abdominal cocoon syndrome) is not well-known by the general surgeon; most reviews of this subject occur in the nephrology literature. Peritoneal dialysis and continuous hyperthermic peritoneal perfusion are the main causes. No controlled study exists to evaluate the optimal therapeutic approach. Pre-operative diagnosis is difficult since the clinical signs and radiologic findings are non-specific. Nevertheless, the diagnosis should be considered when small bowel obstruction with proximal dilatation, ascites, and thickened or calcified peritoneum are seen on imaging. The surgeon should recognize sclerosing peritonitis grossly when it is encountered and adapt his surgical strategy accordingly.

Closed continuous hyperthermic peritoneal perfusion model in mice with peritoneal dissemination of colon 26

An original model of closed continuous hyperthermic peritoneal perfusion (CHPP) in mice is presented and was found to support the efficacy of intraperitoneal hyperthermia. Closed CHPP was performed after intraperitoneal inoculation of transplantable colon 26 cells into a mouse. Colon 26 cells (5 × 104) were injected into 18 mice. The mice were then allocated to six groups of three each and subjected to peritoneal perfusion over time. Peritoneal washings from each mouse were sampled and counted by the cytosmear method. On day 10 after inoculation, colonies of the disseminated tumour were seen on the mesentery by staining with 0.1% methylene blue for 5 min. The number of tumour nodules on the mesentery was counted. The number of washed-out tumour cells decreased the most at 24 h after inoculation, and 76% of the inoculated cells did not wash out during the peritoneal perfusion procedure. CHPP was performed after 24 h when colon 26 cells were injected into the peritoneal cavity because this status may represent micrometastasis. The total number of nodules on the mesentery in the CHPP group was significantly smaller than that in the control (p<0.02). In conclusion, because this treatment model is similar to the clinical CHPP, the biostaining model might be useful for the evaluation of peritoneal dissemination and it was unique and valuable in demonstrating an effective treatment for the prevention of peritoneal dissemination.

Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy.

Malignant mesothelioma (MM) arising in the peritoneal cavity is a rare neoplasm characterized by peritoneal progression and for which there are limited therapeutic options. We evaluated the peritoneal progression-free and overall survival (PFS and OS, respectively) for patients with peritoneal MM after surgical resection and regional chemotherapy. Forty-nine patients (28 males, 21 females; median age, 47 years; range, 16 to 76 years) with MM underwent laparotomy, tumor resection, continuous hyperthermic peritoneal perfusion with cisplatin (median dose 250 mg/m2), and a single postoperative intraperitoneal dwell of fluorouracil and paclitaxel (n = 35) on protocols approved by the Institutional Review Board. Standard techniques for actuarial analyses of potential prognostic variables (Kaplan-Meier method with two-tailed log-rank test and Cox proportional hazards model) were performed. At a median potential follow-up of 28.3 months, median actuarial PFS is 17 months and actuarial OS is 92 months. Factors associated with improved PFS and OS by the Cox proportional hazards model were a history of previous debulking surgery, absence of deep tissue invasion, minimal residual disease after surgical resection (OS only), and age younger than 60 years (OS only). Surgical resection and regional chemotherapy for MM results in durable PFS and OS. Favorable outcome is associated with age, tumor biology (selection of patients with a history of previous debulking), lack of invasive tumor growth, and minimal residual disease after tumor resection.

Lack of efficacy of prophylactic continuous hyperthermic peritoneal perfusion on subsequent peritoneal recurrence and survival in patients with advanced gastric cancer

Background. Peritoneal recurrence is a major cause of death in advanced gastric cancer. Although many kinds of chemotherapy intended to prevent peritoneal recurrence of gastric cancer have been evaluated, few have been successful. Few studies have assessed the clinical significance of continuous hyperthermic peritoneal perfusion in peritoneal recurrence. Methods. From 1992 to 1999, a total of 124 patients with advanced gastric cancer with tumors invading deeper than the serosa but with no peritoneal metastasis underwent potentially curative gastrectomy and were enrolled in this study. Prophylactic continuous hyperthermic peritoneal perfusion (P-CHPP) was performed in 45 patients younger than 65 years old and without comorbidity who gave informed consent. Seventy-nine patients who did not meet the inclusion criteria represented the control group. After reconstruction of the alimentary tract, P-CHPP was carried out for 40 minutes with 150 mg cisplatin, 15 mg mitomycin C, and 150 mg etoposide in 5 to 6 L physiologic saline maintained at 42°C to 43°C. The surgical results, recurrent pattern, and postoperative morbidity were assessed by univariate and multivariate analysis. Results. When compared with patients not undergoing P-CHPP, patients treated by P-CHPP had higher incidences of respiratory failure (73% vs 19%; P <.0001) and renal failure (7% vs 0%; P <.03). Neither 5-year survival (49% vs 56%) nor the patterns of recurrence (peritoneal, hematogenous, and lymphatic) were affected by P-CHPP. Conclusions. P-CHPP by our methods had no efficacy as prophylactic treatment for peritoneal recurrence induced by gastric cancer. New therapeutic strategies, such as chemosensitivity assessment, are necessary to obtain good therapeutic results with CHPP. (Surgery 2002;131:521-8.)

Laparoscopic continuous hyperthermic peritoneal perfusion

Chang, Eugene MDa; Alexander, Richard H. mda; Libutti, Steven K mda; Hurst, Ronald MDa; Zhai, Suoping PhDa; Figg, William D MDa; Bartlett, David L MDa,* Author Information

The use of docetaxel in continuous hyperthermic peritoneal perfusion chemotherapy (CHPPC) for peritoneal recurrence of gynecological malignancies resistant to systemic chemotherapy. A feasibility and pharmacokinetic study

The use of docetaxel in continuous hyperthermic peritoneal perfusion chemotherapy (CHPPC) for peritoneal recurrence of gynecological malignancies resistant to systemic chemotherapy. A feasibility and pharmacokinetic study