Cytoreductive Surgery with Selective Versus Complete Parietal Peritonectomy Followed by Hyperthermic Intraperitoneal Chemotherapy in Patients with Diffuse Malignant Peritoneal Mesothelioma: A Controlled Study Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of an expanded access program. Peritoneal Mesothelioma Treated by Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy: Results of a Prospective Study Morbidity and Mortality Assessment of Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Diffuse Malignant Peritoneal Mesothelioma—A Prospective Study of 70 Consecutive Cases Treatment of Primary Peritoneal Mesothelioma by Continuous Hyperthermic Peritoneal Perfusion (CHPP) A Phase I Trial of Thermal Sensitization Using Induced Oxidative Stress in the Context of HIPEC Continuous hyperthermic peritoneal perfusion with cisplatin for the treatment of peritoneal mesothelioma. Malignant peritoneal mesothelioma: treatment with maximal cytoreductive surgery plus intraperitoneal chemotherapy. Prognostic significance of histomorphologic parameters in diffuse malignant peritoneal mesothelioma. Malignant peritoneal mesothelioma-Results from the International Expanded Access Program using pemetrexed alone or in combination with a platinum agent. Adopting extensive intra-operative peritoneal lavage (EIPL) as the standard prophylactic strategy for peritoneal recurrence. Repeat Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy May Offer Survival Benefit for Intraperitoneal Mesothelioma: A Single Institution Experience Systemic Chemotherapy with Pemetrexed and Cisplatin for Malignant Peritoneal Mesothelioma: A Single Institution Experience Prospective trial for the treatment of malignant peritoneal mesothelioma. Intraperitoneal cancer dissemination: Mechanisms of the patterns of spread Treatment of primary peritoneal mesothelioma by hyperthemic intraperitoneal chemotherapy Cytoreductive surgery and intraperitoneal chemotherapy for peritoneal mesothelioma.
Background Combined treatment involving peritonectomy procedures , multivisceral resections , and hyperthermic intraperitoneal chemotherapy ( HIPEC ) has reportedly result ed in survival benefit for peritoneal surface malignancies , including diffuse malignant peritoneal mesothelioma ( DMPM ) . Many unanswered questions remain regarding the surgical options in the management of DMPM . The aim of this case – control study was to assess the impact of the type and extent of parietal peritonectomy on survival and operative outcomes . Methods Thirty patients with DMPM undergoing selective parietal peritonectomy ( SPP ) of macroscopically involved regions , and 30 matched patients undergoing routine complete parietal peritonectomy ( CPP ) , regardless of disease distribution , were retrospectively identified from a prospect i ve data base . Results Groups were comparable for all characteristics , except for a higher proportion of patients treated before July 2003 and undergoing preoperative systemic chemotherapy in the SPP group . Median follow-up was 86.2 months in the SPP group and 50.3 months in the CPP group . Median overall survival was 29.6 months in the SPP group and not reached in the CPP group ; 5-year overall survival was 40.0 % and 63.9 % , respectively ( P = 0.0269 ) . At multivariate analysis , CPP versus SPP was recognized as an independent predictor of better prognosis , along with complete cytoreduction , negative lymph nodes , epithelial histology , and lower MIB-1 labelling index . Morbidity and reoperation rates were not different between groups . No operative mortality occurred . In 12 of 24 patients undergoing CPP , pathologic examination detected disease involvement on parietal surfaces with no evident tumor at surgical exploration . Conclusions CPP improved survival in patients with DMPM undergoing combined treatment . This information may contribute to st and ardize surgical options for DMPM and other peritoneal malignancies BACKGROUND To date , few large studies have been reported of patients with peritoneal mesothelioma , and treatment of this disease has been largely extrapolated from the treatment of pleural disease . Hence , it was considered important to study and report on this specific patient population . Before the regulatory approval of pemetrexed , an exp and ed access program ( EAP ) provided access to eligible patients with malignant pleural or peritoneal mesothelioma . PATIENTS AND METHODS Patients received pemetrexed 500 mg/m2 alone or in combination with cisplatin 75 mg/m2 once every 21 days for > or = 6 cycles . All patients received folic acid , vitamin B12 , and steroid prophylaxis .  Serious adverse events ( SAEs ) were compiled in a pharmacovigilance data base , which included all patients in the EAP with pleural or peritoneal mesothelioma . From June 12 , 2002 to February 18 , 2004 , 1056 patients with malignant mesothelioma were enrolled and received > or = 1 dose of treatment at 462 sites in the United States . Of these patients , 98 ( 9.3 % ) had peritoneal mesothelioma ( 57 previously treated , 38 chemotherapy-naive , and 3 with missing data ) . RESULTS Response data were available for 73 patients ( 43 previously treated , 28 chemotherapy-naive , and 2 not classified ) , indicating response rates of 23.3 % for previously treated patients ( 0 complete responses [ CRs ] , 10 partial responses [ PRs ] , 21 cases of stable disease [ SDs ] , 12 cases of progressive disease [ PDs ] ) and 25 % for chemotherapy-naive patients ( 3 CRs , 4 PRs , 12 SDs , and 9 PDs ) . Median survival was 13.1 months for previously treated patients and has not been reached for chemotherapy-naive patients . The most commonly reported SAEs for the total EAP were dehydration ( 7.2 % ) , nausea ( 5.2 % ) , and vomiting ( 4.9 % ) . CONCLUSION Pemetrexed with or without cisplatin had a favorable safety profile , and the disease control rate ( CR + PR + SD ) of 71.2 % in the subset of patients with peritoneal mesothelioma indicated activity in this patient population Background Peritoneal mesothelioma is a rare disease with few therapeutic options . Recently , the combination of cytoreductive surgery with intraperitoneal hyperthermic chemotherapy ( HIPEC ) has shown promising results . Methods Fifteen patients with peritoneal mesothelioma who were treated by cytoreductive surgery and HIPEC between 1989 and 2004 were identified from a prospect i ve data base .  HIPEC was performed with cisplatin and mitomycin C for 90 minutes by using the closed-abdomen technique . Results All patients but one ( multicystic ) had malignant disease of the following pathologic types : 12 epithelial and 2 biphasic . After surgical resection , 11 patients were considered to have a CC-0 or CC-1 resection ( macroscopic complete resection or diameter of residual nodules < 2.5 mm ) . No postoperative death occurred , and six postoperative complications were recorded . All but one patient had resolution of ascites . The overall median survival for the 14 patients with malignant mesothelioma was 35.6 months . The median survival was 37.8 months for patients treated with a CC-0 or CC-1 resection , whereas it was 6.5 months for those treated with a CC-2 or CC-3 resection ( diameter of residual nodules > 2.5 mm ; P < .001 ) . In a univariate analysis , the only other significant prognostic factor was the carcinomatosis extent ( P = .02 ) . Conclusions A therapeutic strategy combining cytoreductive surgery with HIPEC seems to provide an adequate and efficient locoregional treatment for peritoneal mesothelioma . It is associated with acceptable morbidity when performed by an experienced surgical team . The completeness of cytoreduction is the major determinant of survival Background Although many reports regarding morbidity and mortality of cytoreductive surgery plus perioperative intraperitoneal chemotherapy are available , there are no prospect i ve data on morbidity and mortality limited to patients with diffuse malignant peritoneal mesothelioma ( DMPM ) . Methods This prospect i ve morbidity and mortality assessment was performed on 70 consecutive cytoreductive procedures with perioperative intraperitoneal chemotherapy for DMPM . Forty-seven adverse events by eight categories were rated from grade s I to IV with increasing severity . Grade I morbidity was self-limiting ; grade II required medical treatments ; grade III required an invasive intervention ; grade IV required returning to the operating room or intensive care management . Risk factors for grade s III and IV morbidity were determined . Results The perioperative mortality rate was 3 % . The grade s III and IV morbidity rates were 27 and 14 % , respectively . Primary colonic anastomosis ( P = 0.028 ) , more than four peritonectomy procedures ( P = 0.015 ) , duration of the operation of more than 7 h ( P = 0.027 ) were the risk factors for grade IV morbidity . Survival analysis of these 70 patients was provided . Conclusions The morbidity and mortality results for cytoreductive surgery and perioperative intraperitoneal chemotherapy for patients with DMPM were within the acceptable range for major gastrointestinal surgery . Grade IV morbidity was associated with more extensive cytoreduction Abstract Background : Primary peritoneal mesothelioma is a locally aggressive disease that is difficult to treat or even palliate . Continuous hyperthermic peritoneal perfusion ( CHPP ) with cisplatin ( CDDP ) allows uniform , high regional delivery of chemotherapeutics and hyperthermia to the peritoneal surface for the treatment of peritoneal tumors . This article summarizes the results of 18 patients with peritoneal mesothelioma treated with CHPP . Methods : From June 1993 through April 1998 , 18 patients with primary peritoneal mesothelioma ( 13 male , 5 female ; median age , 51 years ) underwent surgical exploration and tumor debulking followed by a 90-minute CHPP with CDDP and hyperthermia as part of three consecutive phase I trials conducted at the National Cancer Institute . Seventeen of 18 patients had malignant peritoneal mesothelioma , 13 with associated ascites . One patient had a symptomatic , multiply recurrent , benign , cystic peritoneal mesothelioma . Three patients who had a recurrence after a prolonged progression-free interval ( > 6 months ) after CHPP underwent re-treatment . CHPP parameters included median cisplatin dose of 530 mg ( range , 187–816 ) , perfusate volume 6.0 liter ( range , 4–9 ) , flow 1.5 liter/min ( range , 1–2 ) , intraperitoneal temperature 41 ° C ( range , 38.7–43.2 ) , and central temperature 38.6 ° C ( range , 36.8–39.7 ) . Results : Median follow-up after CHPP is 19 months ( range , 2–56 ) with no operative or treatment-related mortality . Overall operative morbidity was 24 % and included two patients with superficial wound infection and one patient each with atrial fibrillation , pancreatitis , fascial dehiscence , ileus , line sepsis , and clostridium difficile colitis . The major treatment-related toxicity was systemic renal toxicity at doses above what was defined as the maximum tolerated dose of cisplatin . Nine of 10 patients had resolution of their ascites postoperatively . Three patients who developed recurrent ascites ( 27 , 22 , and 10 months after initial treatment ) were re-treated and had resolution of their ascites with ongoing responses at 24 , 6 , and 4 months after the second perfusion . The median progression-free survival was 26 months , and the overall 2-year survival was 80 % . The median overall survival has not been reached . Conclusions : CHPP with cisplatin can be performed safely with no mortality and minimal morbidity . In selected patients , successful palliation in the abdomen and long-term survival , compared with historical controls , can be achieved with aggressive surgical debulking and CHPP . Re-treatment after initial response can result in a second long-term response Background Inducing oxidative stress under hyperthermic conditions significantly decreases tumor cell growth in a murine model of human colon cancer carcinomatosis . This phase I study examines the safety and pharmacokinetics of induced oxidative stress by the addition of hydrogen peroxide ( H2O2 ) to the perfusate in patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy ( HIPEC ) for advanced abdominal-only malignancies . Methods Patients with advanced colon or appendiceal malignancies underwent maximal cytoreduction followed by HIPEC with mitomycin C ( MMC ) . In addition , H2O2 was added to the perfusate at three concentrations ( n = 3/level , 0.05 , 0.075 , 0.1 % ) . A control group consisted of patients perfused with MMC alone ( n = 3 ) . Perfusate , serum MMC , and H2O2 levels were measured , as were tissue levels of MMC . Results Twelve patients were enrolled onto this trial . The median ( range ) peritoneal carcinomatosis index was 13 ( 3–20 ) requiring a median operative time of 6.3 ( 4–8.5 ) h. The median postoperative length of stay was 9 ( 5–34 ) days , with six patients requiring readmission within 30 days . Similar complications were observed at all three H2O2 levels , as well as in the control group . One patient required reexploration for a colon perforation ( control group ) , and three patients developed enterocutaneous fistulas ( 0.075 % H2O2 , 0.1 % H2O2 and control group ) . There were no operative mortalities . Conclusions Hyperthermic intraperitoneal chemotherapy with induced oxidative stress after maximal cytoreduction is well tolerated . On the basis of the encouraging toxicity profile after cytoreduction and HIPEC with induced oxidative stress , a phase II trial to verify activity is indicated PURPOSE Peritoneal mesothelioma remains a difficult therapeutic challenge . Aggressive debulking combined with continuous hyperthermic peritoneal perfusion ( CHPP ) using cisplatin ( CDDP ) is a novel strategy for the treatment of peritoneal mesothelioma , allowing high regional delivery of chemotherapeutics and hyperthermia while minimizing systemic toxicity . PATIENTS AND METHODS From June 1993 to May 1996 , 10 patients with peritoneal mesothelioma ( six men , four women ; mean age 40 years , range 15 - 57 ) underwent tumor debulking followed by a 90-minute CHPP . CHPP parameters included mean initial CDDP of 120 micrograms/mL ( range 81 - 166 ) , perfusate volume 5.2 L ( range 4 - 7 ) , flow 1.5 L/min , intraperitoneal temperature at three locations-41.5 degrees C , 40.5 degrees C , 41.1 degrees C , and core temperature 38.4 degrees C ( range 37.2 degrees C-39.5 degrees C ) . Nine of 10 patients had malignant peritoneal mesothelioma , eight with associated ascites , while the tenth had a symptomatic , multiply recurrent benign peritoneal mesothelioma . Nine of 10 patients were optimally debulked . Pharmacokinetics were performed on blood and perfusate sample s on nine patients ;  CDDP levels were quantitated by atomic absorption spectroscopy . RESULTS Total perfusate cisplatin AUC was a mean of 21-fold higher ( range 2- to 116-fold ) than total serum cisplatin AUC , and serum CDDP  behaved similarly to systemically administered CDDP . Median follow-up after CHPP is 10 months ( range 2 - 32 ) , with no treatment-related mortality . In eight optimally debulked patients there is no evidence of recurrent disease clinical ly or by CT or MRI . Seven patients with symptomatic ascites have been completely palliated . CONCLUSIONS CHPP with CDDP is well tolerated with no significant regional toxicity . Because favorable CDDP pharmacokinetics suggest the potential for enhanced CDDP tumoricidal effect during CHPP , tumor debulking and CHPP may represent an effective strategy for the treatment of peritoneal mesothelioma OBJECTIVE To report survival results in patients with diffuse malignant peritoneal mesothelioma ( MPM ) treated with  maximal cytoreductive surgery followed by immediate intraperitoneal chemotherapy  , and to compare them with the median survival of 12 - 24 months obtained with the st and ard treatment based on systemic chemotherapy . PATIENTS AND METHODS Twenty-six patients underwent this new regional approach and a median follow-up of 55 months was achieved after this treatment . Complete cytoreductive surgery ( residual disease < 2 mm ) was performed in all but one patient . Intraperitoneal chemotherapy was performed with hyperthermia ( 4245 degrees C ) and oxaliplatin in 22 patients . The last 12 patients additionally received irinotecan . Data were prospect ively verified and retrospectively analyzed . RESULTS One patient died postoperatively ( 4 % ) , and morbidity attained 54 % . The median survival exceeded 100 months and the overall 5-year survival rate was 63 % . This small series lacks the statistical power required to conduct a well-grounded study on prognostic factors , particularly as the completeness of the surgery is not analyzable here . However , the low- grade histological types had a better disease-free survival rate that was of borderline significance compared to their high- grade counterparts . CONCLUSION This new approach combining complete cytoreductive surgery considerably increases the survival of patients with MPM compared with the st and ard treatment based on systemic chemotherapy CONTEXT Diffuse malignant peritoneal mesothelioma is currently regarded as a rare and lethal primary tumor arising from the peritoneal membrane . In the past , treatment plans with variable combinations of surgery and systemic chemotherapy were associated with a median survival of approximately 1 year . St and ardized treatments using cytoreductive surgery and perioperative intraperitoneal chemotherapy have extended this survival . OBJECTIVE To critically analyze the prognostic significance of histomorphologic parameters as a determinant of survival . DESIGN Sixty-two consecutive patients with diffuse malignant peritoneal mesothelioma in whom data were prospect ively accumulated were retrospectively analyzed by 14 different histomorphologic parameters . The influences of these pathologic characteristics on survival were critically statistically evaluated . RESULTS In a univariate analysis , histologic type , nuclear/nucleolar size , stroma , depth of invasion into the bowel , atypical mitoses , mitotic index , necrosis , lymph node involvement , and chromatin patterns were found to be significant . In the multivariate analysis , histologic type and nuclear/nucleolar size remained as determinant histomorphologic characteristics . Use of biphasic/sarcomatoid histologic type as a poor prognostic characteristic was limited in that only 8 % of patients showed this histology . CONCLUSIONS Histomorphologic parameters carry prognostic significance in predicting the survival of patients with diffuse malignant peritoneal mesothelioma when treated in a st and ardized fashion using cytoreductive surgery and perioperative intraperitoneal chemotherapy .  Nuclear/nucleolar size was found to be a reliable histomorphologic assessment available to assess prognosis in these patients AIM Peritoneal mesothelioma ( PM ) has rarely been studied . The Exp and ed Access Program ( EAP ) provided access to 109 patients with PM . METHODS This was a nonr and omized , open-label study conducted in chemo-naïve or previously treated patients with PM not amenable to curative surgery . Patients received pemetrexed ( PEM ) 500 mg/m2 alone or with cisplatin ( CIS ) 75 mg/m2 or carboplatin ( CARBO ) AUC 5 every 21 days , supplemented with st and ard vitamin B(12 ) , folate , and dexamethasone . RESULTS Response rates ( 95 % CI ) for PEM , PEM/CIS , and PEM/CARBO were 12.5 % ( 3.5 , 29.0 ) , 20.0 % ( 7.7 , 38.6 ) , and 24.1 % ( 10.3 , 43.5 ) , respectively . Median survival for PEM was 10.3 months . One-year survival rates for PEM/CIS and PEM were 57.4 % ( 95 % CI : 10.3 , 100 ) and 41.5 % ( 95 % CI : 4.6 , 78.4 ) , respectively , and were not available for PEM/CARBO . Anemia was the most common serious adverse event ( 6.4 % ) . Neutropenia ( 34.6 % ) was the most frequent CTC grade 3 or 4 toxicity reported . CONCLUDING STATEMENT PEM with or without a platinum agent was both active and well tolerated in patients with peritoneal mesothelioma EIPL ( extensive intra-operative peritoneal lavage ) therapy was developed as a prophylactic strategy for peritoneal recurrence , with the goal of improving the quality of life and survival span for advanced gastric cancer patients with peritoneal free cancer cells . The purpose of this article is to review the therapy 's contribution to a remarkable improvement in the 5-year survival for patients with positive lavage cytology on prospect i ve r and omized controlled clinical trials . We also advocate for the adoption of the EIPL as the optimal treatment protocol for advanced gastric cancer Introduction Cytoreduction with heated intraperitoneal chemotherapy ( HIPEC ) has demonstrated improved overall survival ( OS ) in malignant peritoneal mesothelioma ( MPM ) . The role of repeated HIPEC for MPM is less clear . Methods An institutional review board-approved data base of MPM patients was analyzed for clinical factors and outcomes . Results From June 2004 to March 2012 , 29 patients underwent surgical treatment for mesothelioma .  HIPEC was aborted in 3 and completed in 26 ; 8 underwent additional repeat HIPEC .  The majority was male ( 62 % ) , median age 66 years . There was no significant difference in surgery duration , blood loss , or hospital-stay- duration between initial and repeat HIPEC . Cisplatin was the chemotherapy used . Complications occurred in 17 ( 65 % ) initial and 6 ( 50 % ) repeat HIPEC , with wound complications being most common . Reoperation was less common ( 4 % initial and 25 % repeat ) , and perioperative death was rare ( 4 % initial , 0 % repeat ) . Fourteen ( 54 % ) initial and seven ( 58 % ) repeat HIPEC patients received adjuvant chemotherapy .  Median time from  HIPEC  to initiation of chemotherapy was not different between initial and repeat HIPEC ( 8.8 and 4.6 months , respectively , p = 0.68 ) . Median treatment-free time ( time from initial to repeat HIPEC or chemotherapy ) also was not different between initial and repeat HIPEC ( 8.8 and 6.3 months , respectively , p = 0.92 ) . Median OS for the cohort was 41.2 months . Patients who underwent repeat HIPEC had improved median OS ( 80 months ) versus single HIPEC ( 27.2 months ; p = 0.007 ) . A lower peritoneal carcinoma index and complete cytoreduction were associated positively with OS . Conclusions Cytoreduction and HIPEC for MPM are associated with longer OS . Patients who are c and i date s for repeat HIPEC may derive an even greater OS advantage Background and aims Primary malignant peritoneal mesothelioma is a rare malignancy with an unfavorable prognosis . Pemetrexed has proven effective in the treatment of malignant mesothelioma , alone or in combination with platinum agents . In the present study , chemo-naïve patients were evaluated for the efficacy and safety of the pemetrexed-cisplatin combination . Methods Six patients with diffuse peritoneal mesothelioma were treated with 6 cycles of pemetrexed ( 500 mg/m2 ) and cisplatin ( 75 mg/m2 ) . Chemotherapy was administered on an outpatient basis every 3 weeks . Results Complete response was observed in 2 patients ( 33 % ) and partial response was observed in 3 patients ( 50 % ) . The estimated median overall survival was 24 months and the estimated median time to disease progression was 9.5 months . The regimen was well tolerated . Conclusions Though our data reflect a small sample size , pemetrexed plus cisplatin accomplished a particularly high clinical benefit rate on chemo-naïve patients . Free full text available at Malignant peritoneal mesothelioma ( MPM ) is a rare and often rapidly fatal disease with median survival of 5 to 12 months for untreated cases and 16 months reported after multimodality treatment . We report a prospect i ve clinical treatment study using cytoreductive surgery combined with intraoperative intraperitoneal heated chemotherapy ( IPHC ) perfusion using mitomycin C for MPM . Twelve patients ( 11 male with a mean age 51 years ) were treated . Seven patients presented with bulky disease and seven with ascites . All underwent exploratory laparotomy with histologically confirmed diagnosis of MPM . Surgical debulking as feasible was performed . Complete gross tumor removal was possible in only one patient . Cytoreduction was followed by a 2-hour closed low-volume IPHC using mitomycin C. One patient died 50 days postoperatively from complications relating to small bowel perforation . Hematologic toxicity of the procedure was minimal . Ascites was controlled in all patients and permanently in 86 per cent of patients presenting with ascites . To date median survival is 34.2 months with median follow-up of 45.2 months . One patient was re-explored for ventral hernia 2 years post-IPHC , had negative peritoneal biopsies , and remains disease-free at 5 years . Given the dismal prognosis associated with MPM the results of treatment with cytoreductive surgery combined with IPHC perfusion are encouraging . The rarity of MPM makes appropriately powered prospect i ve r and omized trials unlikely . Therefore , we now offer this approach off protocol ; however , further study of this combined modality therapy is warranted BACKGROUND Well known patterns govern the distribution of hematogenous and lymphatic metastasis of cancer . In the past the distribution of cancer cells free within abdominal cavity received little attention and was thought to be a r and om event . However , surgical observation led the authors to generate and test hypotheses regarding patterns of spread that vary with tumor type , with the intraperitoneal environment , and with the physiology of the peritoneal surface tissues . METHODS The distribution and volume of peritoneal surface malignancy was prospect ively recorded in 129 patients with 5 different types of tumors at the time of cytoreductive surgery .  The malignancies studied included pseudomyxoma peritonei ( PMP ) of appendiceal origin , colonic mucinous adenocarcinoma ( MA ) , nonmucinous colonic adenocarcinoma ( NMA ) , ovarian carcinoma ( OV ) and sarcoma ( SA ) . The abdominal and pelvic cavity was divided into 3 horizontal sectors , 9 regions and 25 sites . The incidences of tumor implants in these design ated areas were statistically analyzed for each tumor type and comparisons between tumor types studied . RESULTS The magnitude of intraperitoneal cancer dissemination was similar for mucinous tumors , including PMP and MA and significantly higher than for non-mucinous tumors . Also the mucinous cancers were more likely to be present in the upper horizontal sector than were non-mucinous . When NMA was compared to PMP and MA the epigastric region was significantly less likely to contain tumor . For all cancer diagnoses the colon , greater omentum and cul-de-sac of Douglas were most often affected . The ileocecal valve region was more likely to have large tumor masses on its surface than small bowel surface or small bowel mesentery . CONCLUSIONS Peritoneal carcinomatosis had a wider distribution when mucinous fluid was present ; this cancer distribution by intraperitoneal fluid hydrodynamics occurred regardless of histologic aggressiveness . The organs that have peritoneal fluid resorption ( omentum and omental appendages ) have a high incidence of implants . Small bowel and its mesentery free to move by peristalsis had a reduced incidence of implants as compared to the ileocecal area , which is fixed to the retroperitoneum . These observations may facilitate efforts to treat peritoneal surface malignancy Perfusion of the peritoneal cavity with chemotherapy agents under hyperthermic conditions has been utilized by several investigators in the treatment of intra-abdominal malignancies . Based on the concept that hyperthermia may potentiate the cytotoxic effects of chemotherapeutic agents , we embarked on a clinical trial of two-stage peritoneal chemotherapy for patients with primary peritoneal mesothelioma , a neoplasm unresponsive to traditional systemic chemotherapeutic regimens . In stage I , patients underwent surgical debulking of gross disease and placement of an intraperitoneal infusion catheter , through which intraperitoneal chemotherapy was administered for four months . Stage II consisted of debulking of residual tumor , placement of two transabdominal perfusion cannulae and administration of high-dose intraperitoneal chemotherapy at 40 ° C using a simple , disposable perfusion circuit . Flow rates were maintained at 1 l/min , and inflow and outflow temperatures maintained at 42 and 40 ° C , respectively . To date , three patients have undergone both phases of the protocol , with no perioperative complications related to either hyperthermia or end-organ toxicity . One patient died of progressive disease after three months , and two patients are alive and well . One patient developed a small bowel anastomotic leak three weeks after operation . In summary , intraoperative hyperthermic peritoneal chemotherapy may play a role in novel approaches to the treatment of peritoneal malignancies previously unresponsive to traditional chemotherapeutic regimens AIMS Peritoneal mesothelioma is a rare disease and traditionally has been associated with a gloomy prognosis . The present study aim ed to report the outcomes following surgery and intraperitoneal chemotherapy in selected patients with peritoneal mesothelioma . METHODS Clinicopathological features , operative procedures , early outcomes and survival were analysed for 17 consecutive patients who underwent surgery for peritoneal mesothelioma between 1998 and 2007 . Seventeen consecutive patients who underwent surgery for peritoneal mesothelioma between 1998 and 2007 were analysed for clinicopathological features , operative procedures , early outcomes and survival . RESULTS Seventeen patients underwent 18 laparotomies .  Most presented with abdominal distension ( 71 % ) and abdominal pain or discomfort ( 53 % ) . Complete cytoreduction was achieved in 8 patients , major debulking in 8 , and 1 patient had an exploratory laparotomy only due to extensive disease . One patient died on day 30 postoperatively due to a chest infection and pulmonary embolism . The median survival for 8 patients who underwent complete cytoreduction was 3.7 years ( range , 0.7 - 6.9 ) , whereas that for 8 patients with palliative debulking was 1.0 years year ( range , 0.3 - 5.7 ) . Among the 12 patients who had significant ascites as a presenting symptom , 10 reported good palliation of ascites . CONCLUSIONS Cytoreductive surgery combined with intraperitoneal chemotherapy appears to be the optimal treatment for selected patients with peritoneal mesothelioma . Increased familiarity with this condition 's presentation and natural history , and knowledge of available treatment options , will hopefully facilitate treatment of these patients and expedite speedy referral to appropriate treatment centres
Malignant peritoneal mesothelioma is a rare disease , with approximately 800 new patients per year in the United States .
Its natural history is defined by progression restricted to the peritoneal space .
In the past , patients with this disease had a limited lifespan of approximately 1 year .