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.

PC01.01 PRO Intrapleural Chemotherapy Is It the Future?

PC01.01 PRO Intrapleural Chemotherapy Is It the Future?

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,

Ein effektives, multimodales Therapiekonzept zur Behandlung des peritoneal metastasierten Ovarialkarzinom-Rezidivs

Optimal treatment of chemoresistant and recurrent ovarian cancer is debating with second line chemotherapies. For peritoneal carcinomatosis new treatment combining cytoreductive surgery with heated intraperitoneal perioperative chemotherapy (HIPEC) may improve survival. METHODS: Retrospective analysis of 70 patients with peritoneal carcinomatosis from ovarian cancer were performed to evaluate feasibility of second debulking plus hyperthermic peritoneal perfusion (HIPEC) and to identify prognostic factors. HIPEC is performed with Mitomycin (20 mg/m 2 ) plus Mitoxantron (20 mg/m 2 ) at 41.5 °C. RESULTS: The study included 78 procedures in 70 patients from 4/2002 to 5/2006. Rate for complete resection (CC-0 + 1 resection) was 81 %. Procedure relates morbidity was 20.5 % without postoperative mortality. Two year survival rate was 72 %. Independent prognostic factors for survival were the extent of carcinomatosis, the completeness of cytoreduction and performance status. CONCLUSIONS: HIPEC is a standardized and reproducible feasible method. Less extensive disease and the quality of cytoreduction remain an independent factor of better outcome. Morbidity is acceptable. In selected patients HIPEC allows to reach the longest median time survival in recurrent peritoneal carcinomatosis from ovarian cancer.

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.

Efficacy of intraoperative hyperthermic peritoneal perfusion on 60 patients with advanced gastric carcinoma

Efficacy of intraoperative hyperthermic peritoneal perfusion on 60 patients with advanced gastric carcinoma

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.

Clinical study of hyperthermic peritoneal perfusion with oxaliplatin and interleukin-2 combined with chemotherapy for treatment on malignant ascites in eider patients

Objective To evaluate the effects and toxicities of the hyperthermic peritoneal peffusion with oxaliplatin (L-OHP) and interleukin-2 (IL-2) combined with chemotherapy for treatment malignant asci-tes. Methods 42 patients with malignant aacites from assimilation system tumor were catheterized,drained and flushed with L-OHP 85 mg/m2 in 2 000 ～2 500 ml of 5 % glucose and IL-2(2 MU),NRL-001 Double RF tumor hyperthermia system was applied to heat the abdominal part for 60 ～ 120 minutes at an intraperitoneal temperature of 41 -43 ℃ ,next day,all the patients were treated with calcium folinate(CF)0. 2 g/m2 by 2 hours intravenous infusion,5-fluorouracil (5-FU) 0. 4 g/m2 intravenously, followed by 46 hours continuous infusion of 5-FU (1 600 mg/m2), 2 weeks a cycle. Results The overall response rate was 66. 67%, including CR : 6 cases, PR:22 cases, NC:6 cases, and PD:8 cases. MST is 5.6 months. The main toxicity was impatient abdomen ache,paralysis intestinal obstruction. Conclusion Hyperthermic peritoneal perfusion with oxaliplatin and inter-leukin-2 combined with chemotherapy is efficient and safe in the treatment malignant ascites and can improve the quality of life. It is worthing wildly using and research. Key words: Oxaliplatin; Interleukin-2; Hyperthermia; induced; Drug therapy; Ascites

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.

Peritoneal Surface Oncology: A progress report

The Fourth International Workshop on Peritoneal Surface Malignancy took place in Madrid (Spain) on December 2, 3 and 4, 2004. The meeting brought together 132 health care professionals currently working on or interested in the management of peritoneal surface malignancy, from 19 countries. The topics covered included diagnostic pathology, technology of hyperthermic peritoneal perfusion, quantitative prognostic indicators, accreditation of treatment programs, ovarian cancer, gastric cancer, peritoneal mesothelioma, appendiceal mucinous tumors, colorectal cancer, morbidity and mortality, and were presented by 25 invited speakers. This article summarizes the most significant discussion points and conclusions relative to the aforementioned topics. The following consensus points were reached: (1) cytoreductive surgery combined with perioperative intraperitoneal chemotherapy is unquestionably considered the standard of care for mucinous appendiceal tumors with peritoneal spread at the present time; (2) there is a need for standardization in the nomenclature used in this field and as a first step “HIPEC” was chosen as the recommended acronym to be used to refer to hyperthermic intraperitoneal chemotherapy in the future; (3) close international collaboration is needed to advance in the standardization of prognostic indicators, technology for HIPEC, accreditation of peritoneal surface malignancy treatment programs, anesthesia management and pathology, and ad hoc working groups were assembled for some of these issues. Future directions for clinical research in this field, especially in carcinomatosis of colorectal origin were identified and extensively discussed.

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.