Cytoreductive surgery and intraperitoneal chemohyperthermia for peritoneal carcinomatosis arising from gastric cancer. Prognostic Features of 51 Colorectal and 130 Appendiceal Cancer Patients with Peritoneal Carcinomatosis Treated by Cytoreductive Surgery and Intraperitoneal Chemotherapy Morbidity and mortality of early postoperative intraperitoneal chemotherapy as adjuvant therapy for gastric cancer. Prospective randomized trial of early postoperative intraperitoneal chemotherapy as an adjuvant to resectable gastric cancer. Effects of continuous hyperthermic peritoneal perfusion on prognosis of gastric cancer with serosal invasion. High volume intraperitoneal chemotherapy (“Belly bath”) for ovarian cancer Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial. Type-oriented Intraoperative and Adjuvant Chemotherapy and Survival after Curative Resection of Advanced Gastric Cancer Hyperthermic peritoneal perfusion combined with anticancer chemotherapy as prophylactic treatment of peritoneal recurrence of gastric cancer. Adjuvant intraperitoneal chemotherapy with carbon-adsorbed mitomycin in patients with gastric cancer: results of a randomized multicenter trial of the Austrian Working Group for Surgical Oncology. Prophylaxis and treatment of peritoneal carcinomatosis: Intraperitoneal chemotherapy with mitomycin C bound to activated carbon particles Indications for Early Postoperative Intraperitoneal Chemotherapy of Advanced Gastric Cancer: Results of a Prospective Randomized Trial Adjuvant intraperitoneal cisplatin therapy in patients with operated gastric carcinoma: results of a randomized trial. [Efficacy of intraoperative hypotonic peritoneal chemo-hyperthermia combined with early postoperative intraperitoneal chemotherapy on gastric cancer]. Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for advanced gastric cancer [Postoperative intraperitioneal hyperthermic chemoperfusion combined with intravenous chemotherapy for 82 advanced gastric cancer patients]. Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. Adjuvant intraperitoneal cisplatin chemotherapy does not improve long-term survival after surgery for advanced gastric cancer. Intraperitoneal thermochemotherapy for prevention of peritoneal recurrence of gastric cancer. Final results of a randomized controlled study Continuous hyperthermic peritoneal perfusion for the prevention of peritoneal recurrence of gastric cancer: Randomized controlled study Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C Prophylaxis with carbon-adsorbed mitomycin against peritoneal recurrence of gastric cancer
HYPOTHESIS The most common cause of palliative resection and recurrence in gastric cancer is peritoneal seeding . This study evaluates the efficacy of intraperitoneal chemohyperthermia after cytoreductive surgery in patients with peritoneal carcinomatosis arising from gastric cancer . DESIGN Prospect i ve clinical trial . SETTING Surgical department at a university academic hospital . PATIENTS Forty-nine consecutive patients with peritoneal carcinomatosis treated between January 1 , 1989 , and February 29 , 2000 . INTERVENTIONS All patients underwent intraperitoneal chemohyperthermia with mitomycin C ( 40 - 60 mg ) ; 21 patients had previously undergone extensive cytoreductive surgery . MAIN OUTCOME MEASURES Clinicopathologic factors that affect overall survival rates . RESULTS With median follow-up of 99 months , overall median survival was 10.3 months . Two factors were significant independent predictors of survival by multivariate analysis : preoperative ascites ( P = .04 ) and completeness of cancer resection ( CCR ) by cytoreductive surgery ( P<.001 ) . Median survival was 21.3 months for patients with CCR-0 ( macroscopic complete resection ) or CCR-1 ( diameter of residual nodules < 5 mm ) and 6.1 months for patients with CCR-2 ( diameter of residual nodules > 5 mm ) ( P<.001 ) . Four patients survived longer than 5 years . CONCLUSIONS An aggressive management strategy combining intraperitoneal chemohyperthermia with cytoreductive surgery is effective for patients with peritoneal carcinomatosis arising from gastric cancer . In highly selected patients ( good general status , resectable primary tumor , resectable peritoneal carcinomatosis ) , this therapy may result in long-term survival Objective A treatment plan to be used in patients with peritoneal carcinomatosis was devised and tested as a Phase II study . Background Background carcinomatosis from appendical or colorectal cancer has been regarded as a fatal clinical entity . Treatment protocol s have not been reported previously . Methods The authors used cytoreductive surgery and intraperitoneal chemotherapy to treat 181 consecutive patients with peritoneal carcinomatosis . There were 51 patients with colorectal cancer and 130 patients with appendiceal cancer . Mean follow-up is 24 months , with a range of 0 to 149 months . Results Results features that showed prognostic significance included appendiceal versus colorectal primary tumors ( p = 0.0001 ) , grade 1 versus grade s 2 and 3 histopathology ( p = 0.0003 ) , complete versus incomplete cytoreductions ( p = 0.0001 ) , lymph node-negative versus lymph node-positive primary tumors ( p = 0.0001 ) , and volume of peritoneal carcinomatosis present preoperatively for colon cancer ( p = 0.0006 ) . Features with no statistical prognostic significance included preoperative tumor volume for appendiceal cancer , age , sex , number of cycles of chemotherapy , operative time , complications , blood loss , and institution providing treatment . From these prognostic features , four prognostic groups were identified , and 3-year survival was estimated by the product-limit survival method . Group I patients ( n = 76 ) were those with grade 1 histology , no lymph node metastases , and complete cytoreductions ( survival at 3 years = 99 % ) . Group II patients ( n = 23 ) were those with grade 2 or 3 histology , no lymph node metastases , and complete cytoreductions ( 65 % ) . Group III patients ( n = 24 ) had any histology , lymph node metastases , and complete cytoreductions ( 66 % ) . Group IV patients ( n = 58 ) had incomplete cytoreductions ( 20 % ) . Conclusions Conclusions cacinomatosis is a treatable condition in selected patients with the possibility for longterm , disease-free survival Intraperitoneal chemotherapy ( IC ) is emerging as a valuable adjuvant therapeutic modality in patients with gastric cancer . The purpose of this study was to assess morbidity and mortality of early postoperative IC ( EPIC ) in gastric cancer patients . Two hundred forty-eight gastric cancer patients thought to have resectable cancer were r and omized intraoperatively to receive EPIC with mitomycin C on postoperative day 1 and 5-fluorouracil on postoperative days 2 to 5 versus surgery only .  Sixty-four patients who were stage IV at histopathologic examination remain in the analysis . Morbidity and mortality were compared using Fisher 's exact test . All patients completed the therapy . In the study group , overall morbidity was higher than in the control group ( 28.8 % versus 20.3 % , respectively ) , although the difference was not significant ( P = 0.121 ) . Intra-abdominal sepsis without anastomotic leak ( P = 0.008 ) and bleeding ( P = 0.002 ) occurred significantly more often in the study group . Also , 37.6 per cent of patients who received EPIC experienced a variety of minor complications attributable to EPIC .  Postoperative mortality was higher in the study group ( 5.6 % ) than in controls ( 0.8 % ) , but not significantly ( P = 0.299 ) . Patients treated with EPIC  stayed in the hospital an average of 4 days longer ( P = 0.002 ) ; in patients with morbidity , however , there was no difference with the control group . A period analysis of the morbidity demonstrated that it followed the pattern of a learning curve . Surgery with EPIC tended to increase the postoperative morbidity and mortality . The therapy-associated risk must be justified by a significant improvement in survival of treated patients with stage III disease . Selective application of perioperative IC may be indicated OBJECTIVE Surgeons have postulated on numerous occasions that cancer resection may participate in the dissemination of a malignancy . This r and omized trial sought to determine whether a large volume of chemotherapy solution used perioperatively to flood the peritoneal cavity could eliminate microscopic residual disease and thereby improve survival of patients with gastric cancer . SUMMARY BACKGROUND DATA Surgical treatment failures in patients with gastric cancer are confined to the abdomen in most patients . Resection site and peritoneal surface spread , along with liver metastases , are the most common areas of recurrence . Survival and quality of life of patients with gastric cancer would be improved if disease progression at these anatomic sites was reduced . METHODS In a prospect i ve r and omized trial of 248 patients , intraperitoneal mitomycin C on day 1 and intraperitoneal 5-fluorouracil on days 2 through 5 were administered after gastric cancer resection .  Patients who were thought to have stage II or stage III disease were r and omized after resection to surgery alone versus surgery plus early postoperative intraperitoneal chemotherapy . After final pathologic examinations , there were 39 patients with stage I , 50 with stage II 95 with stage III , and 64 with resected stage IV cancer . RESULTS The 5-year survival of the surgery-only group was 29.3 % , and the surgery-plus-intraperitoneal chemotherapy group was 38.7 % ( p = 0.219 ) . In a subset analysis , the patients with stage I , stage II , and stage IV disease showed no statistically significant difference in survival . The 5-year survival rate of patients with stage III disease who underwent surgery only was 18.4 % versus a survival rate of 49.1 % for patients who underwent surgery plus intraperitoneal chemotherapy ( p = 0.011 ) . CONCLUSIONS In a subset analysis , patients with stage III gastric cancer have shown a statistically significant improvement in survival when treated with perioperative intraperitoneal chemotherapy . Further studies in patients with gastric cancer with surgically directed chemotherapy are suggested OBJECTIVE To evaluate the effects of continuous hyperthermic peritoneal perfusion ( CHPP ) together with st and ard chemotherapy on the prognosis of patients with gastric cancer invading the serosa . DESIGN Retrospective study . SETTING University hospital , Japan . SUBJECTS 174 patients who had undergone curative resection for gastric cancer invading the serosa ( T3 ) between 1980 and 1989 , 78 of whom had been r and omised to be treated with CHPP after operation and 96 who received st and ard chemotherapy .  INTERVENTIONS CHPP was done immediately after operation ; 8 - 10 l fluid containing 80 - 100 mg/m2 mitomycin C was perfused at a rate of 100 - 200 ml/minute , and inflow and out flow temperatures were maintained at 44 - 45 degrees C and 40 - 42 degrees C , respectively . This was followed by a st and ard regimen of mitomycin C and 1-(2-tetrahydrofuryl)-5-fluorouracil/uracil ( 1:4 ) ( UFT ) . The control group received the st and ard regimen only . MAIN OUTCOME MEASURES Five year survival and patterns of recurrence in three groups : no lymph node metastases , 1 - 9 , and 10 or more . RESULTS Only in the group with 1 - 9 lymph node metastases was there an appreciable but not significant difference in 5 year survival : 66 % compared with 44 % ( p = 0.084 ) . The mean disease free survival for patients with peritoneal metastases was 30 months in the CHPP group compared with 23 months among the controls . CONCLUSION CHPP improved prognosis in patients with T3 gastric cancer who had only 1 - 9 metastatic lymph nodes Summary The currently accepted therapies for ovarian cancer have produced only limited numbers of extended complete remissions in advanced-stage disease . Studies of high-volume intraperitoneal chemotherapy have been initiated to define the toxicology , pharmacokinetics , and the therapeutic effectiveness of this treatment modality . This technique has been virtually ignored until recently , because little success has been achieved with it except in one study ( Rutledge , 1966 ) , in which large intraperitoneal fluid volumes were used . The general lack of success probably reflects inadequate attention to physiologic and pharmacologic principles of drug distribution and absorption in a space as large as the peritoneal cavity . Biomedical engineers , pharmacologists , and clinicians at the NCI have cooperated in the development of a rational chemotherapy for ovarian cancer . Following mathematical pharmacokinetic modeling and toxicologic studies in rat , a Phase I clinical trial of intraperitoneal methotrexate administered in large volumes of dialysis fluid was initiated . Results in three patients confirm the practicality of this approach , and further investigation is warranted BACKGROUND Promising findings obtained using a weekly regimen of 5-fluorouracil ( 5-FU ) , epidoxorubicin , leucovorin ( LV ) , and cisplatin ( PELFw ) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer ( GISCAD ) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients . METHODS From January 1998 to January 2003 , 400 gastric cancer patients at high risk for recurrence including patients with serosal invasion ( stage pT3 N0 ) and /or lymph node metastasis ( stage pT2 or pT3 N1 , N2 , or N3 ) , were enrolled in a trial of adjuvant chemotherapies ; 201 patients were r and omly assigned to receive the  PELFw regimen , consisting of eight weekly administrations of cisplatin ( 40 mg/m2 ) , LV ( 250 mg/m2 ) , epidoxorubicin ( 35 mg/m2 ) , 5-FU ( 500 mg/m2 ) , and glutathione ( 1.5 g/m2 ) with the support of filgrastim , and 196 patients were assigned to a regimen consisting of six monthly administrations of a 5-day course of 5-FU ( 375 mg/m2 daily ) and LV ( 20 mg/m2 daily , 5-FU/LV ) . Disease-free and overall survival were estimated and compared between arms using hazard ratios ( HRs ) and Kaplan-Meier estimates . All statistical tests were two-sided . RESULTS The 5-year survival rates were 52 % in the PELFw arm and 50 % in the 5-FU/LV arm . Compared with the 5-FU/LV regimen , the PELFw regimen did not reduce the risk of death ( HR = 0.95 , 95 % confidence interval [ CI ] = 0.70 to 1.29 ) or relapse ( HR = 0.98 , 95 % CI = 0.75 to 1.29 ) . Less than 10 % of patients in either arm experienced a grade 3 or 4 toxic episode . Neutropenia ( occurring more often in the PELFw arm ) and diarrhea and mucositis ( more prevalent in the 5-FU/LV arm ) were the most common serious side effects . Nevertheless , only 19 patients ( 9.4 % ) completed the treatment in the PELFw arm and 85 ( 43 % ) patients completed the treatment in the 5-FU/LV arm . CONCLUSIONS Our study found no benefit from an intensive weekly chemotherapy in gastric cancer . The extent of toxicity experienced by the patients in the adjuvant setting suggests that , in gastric cancer , chemotherapy may be more safely administered preoperatively n= 16 ) ; intraoperative chemotherapy and UFT 300 mg/day ( P1 group , n= 13 ) ; or UFT 600 mg/day ( P2 group , n= 17 ) . Patients with an intestinal type of cancer were r and omly assigned to one of three treatment groups : H0 ( n= 17 ) , H1 ( n= 12 ) , and H2 ( n= 12 ) ; each group was subjected to the same protocol s as the P0 , P1 , and P2 groups , respectively , except for the MMC administration route . MMC ( 10 mg/patient ) was administered intraoperatively into the intraperitoneal cavity ( P1 and P2 groups ) or the portal vein ( H1 and H2 groups ) . All patients underwent curative resection . Background factors did not differ significantly among the treatment groups . The overall survival rates were progressively worsened in the order of P2 , P1 , and P0 or H2 , H1 , and H0 , respectively . The survival rate of the P2 group was statistically higher than that of the P0 group ( p < 0.05 ) . The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group ( p < 0.05 ) or H0 group ( p < 0.05 ) , respectively . These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site We have conducted a clinical trial to evaluate the effectiveness of continuous hyperthermic peritoneal perfusion with mitomycin C ( CHPP-M ) as prophylactic treatment of peritoneal recurrence of gastric cancer .  Between January 1983 and October 1985 , 82 patients with macroscopic serosal invasion but no macroscopic peritoneal metastasis undergoing potentially curative resection of gastric cancer , were divided into two groups by r and om sampling : 42 patients were scheduled to receive CHPP-M , while 40 would not receive such treatment . The CHPP-M was administered immediately after closure of the abdomen following gastric resection , while the patient was still on the operating table under general anesthesia . The 5-year survival rate ( 71.5 % of the patients in the CHPP-M group was higher than that ( 59.7 % ) of those in the control group . Although postoperative follow-up periods are not long enough , the longer survival obtained in the patients treated with CHPP-M should be emphasized , since no effective means of preventing peritoneal recurrence of gastric cancer is so far available PURPOSE Previous studies have demonstrated a beneficial effect of intraperitoneally applied mitomycin bound to activated carbon particles ( M-CH ) in preventing intraabdominal recurrence following curative surgery for gastric cancer . The Austrian Working Group for Stomach Cancer , a subgroup of the Austrian Working Group for Surgical Oncology , initiated a multicentric phase III trial to evaluate the safety and efficacy of this treatment regimen . PATIENTS AND METHODS A total of 91 patients with a radically resected gastric cancer infiltrating the serosal surface were r and omly assigned to receive either 50 mg mitomycin bound to a solution of 375 mg carbo adsorbens intraperitoneally before closure of the abdominal wound ( n = 46 ) or served as a surgical control group ( n = 45 ) . Postoperative complications and recurrence-free and overall survival were evaluated to analyze the risks and benefits of this treatment . RESULTS After a median observation period of 597 days ( range , 72 to 1,096 ) , a significantly higher postoperative complication rate was observed in the M-CH group ( 35 % ) compared with the control group ( 16 % ) ( P < .02 ) . In accordance with this finding , the postoperative ( 60 days ) mortality rate was also significantly elevated in the M-CH group ( 11 % v 2 % in the control group ) . Since analysis of overall and recurrence-free survival failed to show any beneficial effect of M-CH therapy , the protocol committee decided to stop further recruitment of patients onto this study . CONCLUSION Adjuvant intraperitoneal therapy of gastric cancer by mitomycin bound to activated carbon particles is associated with an increased rate of postoperative complications . However , no benefit for prognosis following radical resection of locally advanced tumors was observed in this multicenter phase III trial A novel method of prophylaxis and treatment for peritoneal carcinomatosis — mitomycin C bound to activated carbon particles (MMC-CH)—was tested in patients with advanced gastric cancer in a prospect i ve r and omized study . Activated carbon particles are taken up selectively by lymphatic tissues , which seem to be a primary site of peritoneal carcinomatosis in the peritoneal cavity , and adsorb a large amount of anticancer agent mitomycin C , which is subsequently released slowly and for a protracted period . A group of 113 patients who underwent radical resection for gastric cancer with definite serosal involvement were entered in this trial . Those in the control group received no intraperitoneal anticancer drugs . Patients in the MMC-CH group were given 50 mg mitomycin C as MMC-CH , which was dispersed throughout the peritoneal cavity just before surgical closure . No other anticancer drugs were given to these patients after surgery . The 2- and 3-year survival rates for the MMC-CH group were 42 % and 38 % , respectively ; and the rates for the control group were 28 % and 20 % , respectively . The difference in survival between the two groups was significant at 2 and 3 years ( p<0.05 ) . For the survival of patients with macroscopic peritoneal carcinomatosis , there was no difference between these two groups . For the survival of patients who underwent histologically curative resection , 2- and 3-year survivals for the MMC-CH group were 66 % and 66 % , respectively and for the control group 35 % and 20 % , respectively . The difference between the two groups was statistically significant ( p<0.01 ) at both 2 and 3 years . There was no difference in morbidity after surgery between these two groups , except a bowel ( colocutaneous ) fistula developed in two patients given MMC-CH . There were no operative deaths in this series . RésuméUne nouvelle méthode prophylactique et thérapeutique de la carcinose péritonéale , l'administration de la mitomycine C liée aux particules de carbone activé ( MMC-CH ) , a été testée chez les patients ayant un cancer gastrique au stade avancé dans une étude prospect i ve , r and omisée . Les particules de carbone activé sont absorbées sélectivement par le courant lymphatique qui semble être le premier site de l'atteinte carcinomateuse de la cavité péritonéale . Ceci permet la résorption d'une gr and e quantité de mitomycine C qui est ensuite relarguée lentement pendant une période de temps prolongé . Cent treize patients ayant eu une résection radicale pour cancer gastrique avec une atteinte séreuse sont rentrés dans cet essais . Ceux du groupe contrôle n'ont reçu aucune autre chimiothérapie . Les patients du groupe MMC-CH  ont reçu 50 mg de mitomycine C sous forme de MMC-CH , dispersée dans la cavité péritonéale juste avant la fermeture . Aucun autre médicament chimiothérapeutique a été administré à ces patients après la chimiothérapie intrapéritonéale : La survie à deux et à trois ans dans let groupe MMC-CH a été de 42 et de 38 pour-cent , respectivement , alors que les taux de survie du groupe contrôle étaient de 28 et de 20 pour-cent , respectivement . La différence de survie à 2 et à ans était statistiquement significantive ( p<0.05 ) . Chez les patients ayant une carcinose péritonéale macroscopique , les taux de survie ne présentaient aucune différence statistiquement significative entre les deux groupes . La survie à 2 et à 3 ans des patients ayant eu une résection histologiquement curative , étaient de 66 % et 66 % pour le groupe MMC-CH , et de 36 et de 20 pour-cent , respectivement . La différence entre les deux groupes était statistiquement significative ( p<0.01 ) à 2 et à 3 ans . II n'y avait aucune différence de morbidité après chirurgie dans les deux groupes excepté le développement de deux fistules intestinales ( colo-cutanée ) chez deux patients du group MMC-CH . II n'y avait aucune mortalité dans cette série . ResumenSe ensayó un novel método de profilaxis y tratamiento de la carinomatosis peritoneal , la mitomicina C ligada a partículas activadas de carbón ( MMC-CH ) , fue probado en pacientes con cáncer gástrico avanzado en un estudio prospect ivo y r and omizado . Las Partículas activadas de carbón son tomadas en forma selectiva por los tejidos linfáticos , los cuales parecen ser una ubicación primaria de la carcinomatosis peritoneal , y absorben una gran cantidad del agente anticancerígeno , la mitomicina C , la cual es subsiguientemente liberada en forma lenta y durante un periodo prolongado . 113 pacientes sometidos a resección radical por cáncer gástrico con clara afección de la serosa fueron ingresados al estudio . Los pcientes del grupo control no recibieron drogas anticancerígenas intraperitoneales . Los pacientes en el grupo MMC-CH recibieron 50 mg de mitomicina C como MMC-CH , que se dispersó a través de la cavidad peritoneal justo antes de iniciar el cierre de la herida . No se administró agente anticancerígeno diferente luego de la cirugía . Las tasas de sobrevida a 2 y 3 años para el grupo MMC-CH fueron 42 y 38 % respectivamente , y las del grupo control fueron 28 y 20 % respectivamente . La diferencia en sobrevida entre estos dos grupos fue significativa a los 2 y 3 años ( p<0.05 ) . No se encontró diferencia entre los dos grupos en los pacientes que sobrevivieron con carcinomatosis peritoneal macroscópica . En la supervivencia de pacientes que recibieron resección histológicamente curativa , las tasas de sobrevida a 2 y 3 años para el grupo MMC-CH fueron 66 y 66 % respectivamente y para el grupo control 35 y 20 % respectivamente . La diferencia entre los dos grupos fue estadísticamente significative ( p<0.01 ) a los 2 y 3 años . No se halló diferencia en cuanto a morbilidad postoperatoria entre estos dos grupos , excepto por fístula del colon ( fístula colo-cutánea ) que apareció en dos pacientes del grupo MMC-CH . No se registraron muertes operatorias en la serie Previous analysis of this prospect i ve r and omized trial and meta- analysis of published r and omized trials of adjuvant intraperitoneal chemotherapy demonstrated improved survival in patients with advanced gastric cancer . Simple criteria applicable at the time of surgery for patient selection were sought in this analysis . From 1990 to 1995 a series of 248 patients with biopsy-proven gastric cancer were r and omized intraoperatively to receive early postoperative intraperitoneal mitomycin C and 5-fluorouracil ( 125 patients ) versus surgery only ( 123 patients ) . Gastric resection plus early postoperative intraperitoneal chemotherapy showed improved overall survival compared to surgery only ( 54 % and 38 % , respectively ; p= 0.0278 ) . There were statistically significant differences in patients with stage III ( 57 % and 23 % , respectively ; p= 0.0024 ) and in those with stage IV ( 28 % and 5 % , respectively ; p= 0.0098 ) gastric cancer . The improvement in survival rate was statistically significant for the subgroup of patients with gross serosal invasion ( 52 % and 25 % , respectively ; p= 0.0004 ) and patients with lymph node metastasis ( 46 % and 22 % , respectively ; p= 0.0027 ) . The surgeons ' impression about lymph node status was unreliable , but assessment of serosal invasion was accurate in 80 % of cases . Gross serosal invasion with or without frozen section evaluation of lymph nodes can be used as the major selection criteria for early postoperative intraperitoneal chemotherapy of advanced gastric cancer In a multicenter trial the efficacy of intraperitoneal administration of cisplatin after radical or palliative resection of gastric carcinoma with respect to overall survival was investigated . In 64 r and omised patients , patients treated with intraperitoneal perfusion did not show a benefit in the overall survival after a median follow-up of 18 months BACKGROUND & OBJECTIVE Abdominal recurrence from exfoliated cancer cells contributes a lot to treatment failure of advanced gastric cancer .  Intraperitoneal chemotherapy , which has been proved effective in eliminating exfoliated cancer cells in abdominal cavity , is a hot topic on treatment of gastric cancer . This study was to explore application of combined therapy of intraoperative hypotonic peritoneal chemo-hyperthermia and early postoperative intraperitoneal chemotherapy to gastric cancer . METHODS A total of 156 gastric cancer patients were r and omized into 3 groups , and underwent the combined therapy ( treatment group 1 ) , intraoperative chemotherapy ( treatment group 2 ) , and peritoneal lavage with distilled water ( control group ) , respectively . RESULTS The 2-year survival rate of treatment group 1 was significantly higher than that of control group ( 88.4 % vs. 65.2 % , P < 0.05 ) . The 3-year survival rate of treatment group 1 was significantly higher than those of treatment group 2 , and control group ( 71.1 % vs. 50.0 % , and 45.6 % , P < 0.05 ) . Occurrence of liver metastasis was significantly lower in treatment groups 1 and 2 than in control group ( 7.7 % , and 10.2 % vs. 27.3 % , P < 0.05 ) . CONCLUSIONS Combined therapy of intraoperative hypotonic chemo-hyperthermia and early postoperative intraperitoneal chemotherapy is effective for gastric cancer . Intraperitoneal chemotherapy can be used to prevent postoperative liver metastasis of gastric cancer Peritoneal carcinomatosis is a common and universally fatal sequelae of gastric carcinoma . Treatment of peritoneal carcinomatosis from appendiceal and colorectal sources with intraperitoneal hyperthermic chemotherapy ( IPHC ) combined with aggressive cytoreductive surgery has been shown to be effective . There are few data on this treatment modality for carcinoma of the stomach . This study evaluates cytoreductive surgery and IPHC with peritoneal carcinomatosis from gastric carcinoma . Thirty-four patients with peritoneal carcinomatosis due to gastric carcinoma underwent gastric resection with cytoreductive surgery followed by IPHC with mitomycin C. A control group consisting of 40 contemporaneous patients , who underwent radical gastrectomy without extended nodal resection , was identified through the tumor registry . Despite more advanced disease in the IPHC group compared to the control group ( P < 0.001 ) , overall survival in the two groups was similar . Proportional-hazards regression analysis shows that only resection status is significantly correlated with improved survival ( P = 0.0068 ) . Within the IPHC group , patients who underwent an R0/R1 resection had increased survival times ( 11.2 vs. 3.3 months , P = 0.015 ) vs. those who underwent R2 resection . The group who had an R0/R1 resection had 1- and 2-year survival rates of 45 % and 45 % compared to 16 % and 8 % , respectively , in the R2 group . Cytoreductive surgery and IPHC is a modality with limited potential for the treatment of peritoneal carcinomatosis from gastric carcinoma . Careful patient selection for this procedure is imperative , and patients in whom an R0/R1 resection can be achieved are the best c and i date OBJECTIVE To evaluate the efficacy of postoperative intraperitoneal hyperthermic chemoperfusion ( IHCP ) combined with intravenous chemotherapy for advanced gastric cancer . METHODS Eighty-two patients with stage II - IV gastric cancer were postoperatively r and omized into two groups ; 46 patients in treatment group who received IHCP combined with intravenous chemotherapy for three times and 36 patients in control group who received intravenous chemotherapy only for six times . All patients in the two groups received the same chemo-regimen LFAP ( CF + 5-Fu + THP or MIT + PDD ) 21 - 28 days after operation . RESULTS The 1-year survival rate was 98 % ( 45/46 ) in the treatment group and 94 % ( 34/36 ) in the control group without any significant difference ( P > 0.05 ) . The 3-year survival rate was 83 % ( 38/46 ) in the treatment group and 61 % ( 22/36 ) in the control group with significant difference ( P < 0.05 ) . Gastrointestinal reaction in the treatment group was significantly decreased compared with in the control group ( 37 % vs 80 % , P < 0.01 ) , whereas no statistically significant difference was noted in bone marrow suppression ( P > 0.05 ) . CONCLUSION Intraperitoneal hyperthermic chemoperfusion combined with intravenous chemotherapy can prolong survival and reduce gastrointestinal side-effect which provides an effective treatment option for advanced gastric cancer BACKGROUND / AIMS Although the most frequent cause of death after curative resection of advanced gastric cancer is peritoneal recurrence , there was no effective therapy for the prevention of peritoneal recurrence . This r and omized trial sought to determine whether intraoperative chemohyperthermic peritoneal perfusion could eliminate microscopic residual disease and thereby improve survival of patients with advanced gastric cancer . METHODOLOGY One-hundred and thirty-nine patients with T2 - 4 gastric cancer underwent curative gastrectomy with extended lymphadenectomy .  These patients were r and omly allocated into the following three groups . Patients in the CHPP group received surgery + chemohyperthermic peritoneal perfusion , and those in the CNPP group underwent surgery + chemonormothermic peritoneal perfusion . The third group was surgery alone group . In the CHPP and CNPP groups , peritoneal cavity was perfused with 6 - 8 liters of heated saline at , respectively , 42 - 43 degrees C and 37 degrees C with 30 mg of mitomycin C and 300 mg of cisplatin by a extracorporeal circulation machine . RESULTS Major operative complication occurred in 19 % ( 9/48 ) , 14 % ( 6/44 ) and 19 % ( 9/47 ) of the CHPP , CNPP and surgery alone group , respectively . Complication which uniquely developed after chemohyperthermic peritoneal perfusion was bowel perforation . Mortality rates of each group were 4 % ( 2/48 ) , 0 % ( 0/44 ) and 4 % ( 2/47 ) in the CHPP , CNPP and surgery alone group , respectively . Overall 5-year survival rates of CHPP , CNPP and surgery alone groups were 61 % , 43 % and 42 % , respectively . In a subset analysis , patients with gastric cancer having serosal invasion or lymph node metastasis have shown a statistically significant improvement in survival when treated with chemohyperthermic peritoneal perfusion . However , chemonormothermic peritoneal perfusion had no survival benefit . By analyzing with Cox proportional hazard model , chemohyperthermic peritoneal perfusion emerged as an independent prognostic factor for good survival . Surgery alone had three-fold higher risk of death than chemohyperthermic peritoneal perfusion . CONCLUSIONS Chemohyperthermic peritoneal perfusion had an efficiency for the prophylaxis of recurrence after curative resection of advanced gastric cancer , and is indicated for patients with tumor infiltrating beyond serosal layer and node positive tumor PURPOSE To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy ( HIPEC ) is superior to st and ard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin . PATIENTS AND METHODS Between February 1998 and August 2001 , 105 patients were r and omly assigned to receive either st and ard treatment consisting of systemic chemotherapy ( fluorouracil-leucovorin ) with or without palliative surgery , or experimental therapy consisting of aggressive cytoreduction with HIPEC , followed by the same systemic chemotherapy regime . The primary end point was survival . RESULTS After a median follow-up period of 21.6 months , the median survival was 12.6 months in the st and ard therapy arm and 22.3 months in the experimental therapy arm ( log-rank test , P = .032 ) . The treatment-related mortality in the aggressive therapy group was 8 % . Most complications from HIPEC were related to bowel leakage . Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions ( log-rank test , P < .0001 ) . If the cytoreduction was macroscopically complete ( R-1 ) , the median survival was also significantly better than in patients with limited ( R-2a ) , or extensive residual disease ( R-2b ; log-rank test , P < .0001 ) . CONCLUSION Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin . However , patients with involvement of six or more regions of the abdominal cavity , or grossly incomplete cytoreduction , had still a grave prognosis PURPOSE The long-term survival probability of patients who undergo surgery for stage 3 and 4 gastric cancer is poor , predominantly due to metastatic spread of the tumor . Depending on the type of tumor histology , the pathway of metastases is mainly peritoneal or hepatic dissemination . Interruption of this mechanism may be possible by intraperitoneal chemotherapy ( IPT ) . PATIENTS AND METHODS In a prospect i ve r and omized trial of 67 patients undergoing surgery for stage 3 and 4 gastric cancer , 33 patients underwent adjuvant postoperative IPT with cisplatin , while 34 control subjects remained untreated .  RESULTS Patients in the treatment group received a median of four IPT perfusions . Apart from frequent nausea , no adverse reactions or complications were noted . The median disease-free survival duration s were 12.7 months and 9.7 months in treated patients and controls , respectively ( P = .8 ) . After a median follow-up duration of 72 months , 54 patients ( 80 % ) had died of primary disease or related complications . The median survival duration for IPT patients was 17.3 months as compared with 16.0 months for controls ( P = .6 ) . Autopsies were performed on 12 ( 18 % ) of 54 patients who died , and showed tumor spread to the peritoneal cavity and /or to the liver , irrespective of the application of IPT . CONCLUSION IPT with cisplatin monotherapy does not improve survival probability after surgery for stage 3 and 4 gastric cancer . The reasons for ineffectiveness of IPT may be the choice of an unsuitable chemotherapeutic agent , an inefficient modus of application , or a lack of sufficient drug penetration into the serosa or peritoneal metastasis Background . Continuous hyperthermic peritoneal perfusion ( CHPP ) with a solution that contained 10 μg/ml mitomycin C was devised initially as a method for intraperitoneal thermochemotherapy . The authors conducted a r and omized clinical trial to evaluate the efficacy of  CHPP  as a prophylactic treatment for prevention of peritoneal recurrence of gastric cancer with serosal invasion We performed continuous hyperthermic peritoneal perfusion ( CHPP ) or continuous normothermic peritoneal perfusion ( CNPP ) combined with cisplatin ( CDDP ) 300 mg/kg and mitomycin C ( MMC ) 30 mg/kg in an attempt to prevent peritoneal recurrence after surgery for gastric cancer . Twenty-two patients were treated with perfusion  using about 10 liters of saline heated to 41 ° to 42 ° C ( CHPP group ) ;  18 patients were treated with saline heated to 37 ° to 38 ° C ( CNPP group ) ; and 18 patients underwent only gastric surgery without perfusion ( control group ) in a r and omized control study . There were two deaths ( 9 % ) due to peritoneal recurrence in the CHPP group , four ( 22 % ) in the CNPP group , and four ( 22 % ) in the control group . The 1- , 2- , and 3-year survival rates were 95 % , 89 % , and 68 % , in the CHPP group ; 81 % , 75 % , and 51 % , in the CNPP group ; and 43 % , 23 % , and 23 % , in the control group , respectively . There was a significant difference between the three survival curves by the log-rank test ( p<0.01 ) . This difference showed that CNPP and CHPP are both effective procedures for preventing peritoneal recurrence . The maximum concentrations in the perfusate of total and free CDDP with 300 mg administration were 12.2 and 10.1 μg/ml , respectively , at the end of the perfusion , and the maximum concentrations of total and free CDDP in plasma were 2.1 and 1.0 μg/ml , respectively . The maximum concentrations of MMC in perfusate and plasma with 30 mg administration were 1.00 and 0.05 μg/ml , respectively , which are intraperitoneally cytotoxic but systemically safe concentrations . RésuméNous mettons en place une perfusion intrapéritonéale hyper ( PPHC ) ou isothermique continue ( PPNC ) , associée à une chimiothérapie combinée ( cisplatine ( CDDP ) à la posologie de 300 mg/Kg et mitomycine C ( MMC ) à la posologie de 30 mg/Kg ) dans le but de prévenir les récidives péritonéales après chirurgie pour cancer gastrique . Dans une étude r and omisée , 22 patients ont été traités par perfusions péritonéale avec 10 liters de sérum physiologique chauffé à 41–42 ° C ( PPHC ) , 18 ont été traités avec du sérum à 37 ° C ( PPNC ) et 18 ont été opérés de leur cancer gastrique  sans perfusion postopératoire ( groupe contrôle ( 22 % ) ) . Les survies à 1 , 2 et 3 ans étaient de 95 , 89 et 68 % , respectivement dans le groupe PPHC , de 81 , 75 et 51 % dans le groupe PPNC et de 43 , 23 et 23 % dans le groupe contrôle . Les trois courbes de survie différaient de façon significative ( logrank p<0.01 ) . Ces différences montrent que non seulement la perfusion intrapéritonéale associée à la chimiothérapie mais aussi l'hyperthermie intrapéritonéale sont efficaces pour prévenir la récidive péritonéale . après résection gastrique pour cancer . Les concentrations maximales globales et isolées de CDDP  étaient de 12.2 et de 10.1 μg/ml à la fin de la perfusion . Les concentrations plasmatiques maximales de MMC globales et isolées étaient de 1.00 et de 0.05 μg/ml . , respectivement . Ces résultats cliniques favorables démontrent que les concentrations obtenues ainsi ne sont pas nocives . ResumenEn pacientes sometidos a cirugía por cáncer gástrico hemos realizado perfusión peritoneal hipertérmica continua ( PPHC ) o perfusión peritoneal normotérmica continua ( PPNC ) combinada con cisplatino ( CCDP ) en dosis de 300 mg/cuerpo y mitomicina C ( MMC ) en dosis de 30 mg/cuerpo con miras a prevenir la recurrencia peritoneal . Veintidós pacientes fueron tratados con perfusión de alrededor de 10 litros de solución salina calentada a 41–42 ° C ( grupo PPHC ) ; 18 pacientes fueron tratados con solución salina calentada a 37–38 ° C ( grupo PPNC ) ; y 18 pacientes fueron sometidos a cirugía gástrica solamente , sin perfusión , los cuales constituyeron el grupo de control . El estudio fue r and omizado . Las muertes por recurrencias peritoneales fueron dos ( 9 % ) en el grupo PPHC , cuatro ( 22 % ) en el grupo PPNC y cuatro ( 22 % ) en el grupo control . Las tasas de sobrevida a uno , dos y tres años fueron 95 % , 89 % y 68 % en el grupo PPHC ; 81 % , 75 % y 51 % en el grupo PPNC ; y 43 % , 23 % y 23 % en grupo control , respectivamente . Se encontró una diferencia significativa en las tres curvas de sobrevida en la prueba de log-rank ( p<0.01 ) . La significativa diferencia hallada entre las tres curvas de sobrevida demuestran que , no sólo la perfusión intraperitoneal combinada con quimioterapia ( PPNC ) sino también la hipertermia intraperitoneal ( PPHC ) , son procedimientos efectivos para la prevención de la recurrencia peritoneal . Las concentraciones máximas del CCDP total y libre en el líquido de perfusión en el régimen de 300 mg fue 12.2 y 10.1 μg/ml al final de la perfusión . Las máximas concentraciones plasmáticas de CDDP total y libre fueron 2.1 y 1.0 μg/ml al final de la perfusión . Las concentraciones máximas de MMC en el líquido de perfusión y en el plasma en regímenes por debajo de 30 mg fueron 1.0 y 0.05 μg/ml . Tales result ados demuestran concentraciones intraperitoneales citotóxicas pero sistémicamente seguras The majority of advanced gastric carcinoma patients with serosal invasion die of peritoneal recurrence , even when a curative gastrectomy is performed , because peritoneal recurrence occurs due to intraperitoneal free tumor cells that detach from the serosal‐invaded focus . In an attempt to prevent peritoneal recurrence , intraperitoneal hyperthermic chemoperfusion ( IHCP ) treatment was combined with aggressive surgery BACKGROUND A regimen of epirubicin , cisplatin , and infused fluorouracil ( ECF ) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma . We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer . METHODS We r and omly assigned patients with resectable adenocarcinoma of the stomach , esophagogastric junction , or lower esophagus to either perioperative chemotherapy and surgery ( 250 patients ) or surgery alone ( 253 patients ) . Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin ( 50 mg per square meter of body-surface area ) and cisplatin ( 60 mg per square meter ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 200 mg per square meter per day ) for 21 days . The primary end point was overall survival . RESULTS  ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer .  Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group ( 46 percent and 45 percent , respectively ) , as were the numbers of deaths within 30 days after surgery . The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group . With a median follow-up of four years , 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died . As compared with the surgery group , the perioperative-chemotherapy group had a higher likelihood of overall survival ( hazard ratio for death , 0.75 ; 95 percent confidence interval , 0.60 to 0.93 ; P=0.009 ; five-year survival rate , 36 percent vs. 23 percent ) and of progression-free survival ( hazard ratio for progression , 0.66 ; 95 percent confidence interval , 0.53 to 0.81 ; P<0.001 ) . CONCLUSIONS In patients with operable gastric or lower esophageal adenocarcinomas , a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival . ( Current Controlled Trials number , IS RCT N93793971 [ controlled-trials.com ] . ) Continuous hyperthermic peritoneal perfusion ( CHPP ) with a solution that contains mitomycin C ( CHPP‐M ) has been clinical ly introduced as a prophylactic treatment for peritoneal recurrence of gastric cancer with serosal invasion . Two studies , each with a treated and a control group , were performed . In the historical control study the postoperative 3‐year survival rate of patients ( 73.7 % ) in the treated group ( n = 38 ) was significantly higher than the survival rate ( 52.7 % ) of those in the control group ( n = 55 ) ( P < 0.04 ) . In the r and om control study the survival rate ( 83 % ) of patients in the treated group ( n = 26 ) was also higher than that ( 67.3 % ) of those in the control group ( n = 21 ) in the 30 months that followed gastric surgery . However , there was no significant difference . In the historical control study with respect to the postoperative complications , anastomotic leak was observed in 8.5 % of patients who were given CHPP‐M and 12.8 % patients who did not have CHPP‐M. In the r and om control study anastomotic leak was observed in 3.1 % of patients who had CHPP‐M and 7.1 % of patients who did not have CHPP‐M. The incidence of adhesive ileus in patients having CHPP‐M did not increase in historical or r and om control groups . Postoperative prolonged intestinal paresis or chemical peritonitis were not induced by CHPP‐M. These results indicate that CHPP‐M is a simple , safe , and readily available prophylactic therapy for peritoneal recurrence that may follow gastric cancer surgery Attempts to prevent peritoneal carcinomatosis after surgery for gastric cancer by intraperitoneal administration of anticancer drugs have not been successful , largely because the drugs are not retained in the peritoneal cavity . We have assessed the prophylactic efficacy of a delayed-release preparation -- mitomycin adsorbed onto activated charcoal ( M-CH ) . 50 patients with gastric cancer and serosal infiltration were r and omly assigned intraperitoneal treatment with M-CH ( 50 mg mitomycin intraoperatively ) or no anticancer prophylaxis ( control ) . Survival rates for the 3 years of follow-up were significantly higher among the 24 M-CH recipients ( 1 was lost to follow-up ) than among the 25 controls ( p less than 0.01 ) . There were significant differences in survival between the groups at 1.5 years after r and omisation ( difference 34.6 % [ 95 % confidence interval 8.5 - 60.8 % ] ; p less than 0.01 ) and at 2.0 , 2.5 , and 3.0 years ( 41.7 % [ 14.2 - 69.1 % ] ; p less than 0.005 ) . The concentration of mitomycin was significantly higher in peritoneal exu date than in plasma for 24 h after drug administration . Side-effects were slight and well tolerated . Thus , peroperative intraperitoneal treatment with M-CH seems to improve survival after gastrectomy for gastric cancer , presumably by a prophylactic effect on peritoneal recurrence
Background The purpose of this systematic review and meta- analysis was to determine the effectiveness and safety of adjuvant intraperitoneal chemotherapy for patients with locally advanced resectable gastric cancer .