Predicting Postoperative Morbidity Following Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CS+HIPEC) with Preoperative FACT-C (Functional Assessment of Cancer Therapy) and Patient-Rated Performance Status Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis A prospective multicenter phase II study evaluating multimodality treatment of patients with peritoneal carcinomatosis arising from appendiceal and colorectal cancer: the COMBATAC trial Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. Cytoreduction and heated intraperitoneal chemotherapy for colorectal cancer: are we excluding patients who may benefit? Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion BEV-IP: Perioperative chemotherapy with bevacizumab in patients undergoing cytoreduction and intraperitoneal chemoperfusion for colorectal carcinomatosis Impact of Aggressive Histology and Location of Primary Tumor on the Efficacy of Surgical Therapy for Peritoneal Carcinomatosis of Colorectal Origin Predictors of Progression in High-Grade Appendiceal or Colorectal Peritoneal Carcinomatosis After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Perioperative systemic chemotherapy in peritoneal carcinomatosis of lymph node positive colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Factors predicting survival after intraperitoneal hyperthermic chemotherapy with mitomycin C after cytoreductive surgery for patients with peritoneal carcinomatosis. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. Intraperitoneal Vascular Endothelial Growth Factor: A Prognostic Factor and the Potential for Intraperitoneal Bevacizumab Use in Peritoneal Surface Malignancies Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. Is There a Possibility of a Cure in Patients With Colorectal Peritoneal Carcinomatosis Amenable to Complete Cytoreductive Surgery and Intraperitoneal Chemotherapy? Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy With Mitomycin C for Peritoneal Carcinomatosis from Nonappendiceal Colorectal Carcinoma Cytoreductive surgery followed by intra peritoneal hyperthermic perfusion in the treatment of peritoneal surface malignancies: morbidity and mortality with closed abdomen technique. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. Identification of a Subgroup of Patients at Highest Risk for Complications After Surgical Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. Intraperitoneal vascular endothelial growth factor burden in peritoneal surface malignancies treated with curative intent: the first step before intraperitoneal anti-vascular endothelial growth factor treatment? Postoperative infections after cytoreductive surgery and HIPEC for peritoneal carcinomatosis: proposal and results from a prospective protocol study of prevention, surveillance and treatment.
Background Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy ( CS+HIPEC ) is associated with significant perioperative morbidity . One goal of our ongoing patient-reported health-related quality of life ( HRQoL ) program is to describe the prognostic value of HRQoL measures for predicting postoperative morbidity and mortality following CS+HIPEC . Methods A retrospective analysis of a prospect ively collected clinical data base for all patients treated for peritoneal carcinomatosis and who participated in our patient-reported HRQoL program from 2001 to 2011 was done . Patients completed the Functional Assessment of Cancer Therapy question naire plus the colon symptom subscale , in addition to the Eastern Cooperative Oncology Group ( ECOG ) performance status rating prior to CS+HIPEC . The trial outcome index ( TOI ) , a specific measure of function , symptoms , and physical well being of the patient , was analyzed . The TOI is a combination of the physical and functional well being subscales + the colon-specific subscale of the FACT-C. Results Of 855 patients , 387 ( 45.2 % ) participated in the HRQoL trials . Mean age was 53.3 years , and 213 ( 55 % ) were female versus 174 ( 45 % ) males . There were 240 patients ( 62 % ) who had a complication versus 147 ( 38 % ) who had no complication . A 30-day mortality rate of 7.7 % ( 30 ) was documented . Patients who suffered a 30-day postoperative mortality demonstrated a lower mean preoperative score in the FACT-C TOI 52.7 versus 61.7 ; P < 0.001 . Independent predictors of 30-day mortality on multivariate analysis included TOI ( 0.05 ) , age ( 0.001 ) , and smoking ( 0.001 ) . Patients with a higher TOI score were less likely to suffer a mortality ( 95 % CI 0.9–1.0 , P = 0.05 ) . Patients with a higher emotional well being ( EWB ) score were less likely to suffer a complication 0.9 ( 95 % CI 0.87–1.0 , P = 0.04 ) . Other independent predictors of postoperative morbidity included diabetic status ( P = 0.05 ) , ECOG performance status ( 0.001 ) , and gender ( 0.02 ) . Conclusions Preoperative HRQoL , as measured by FACT-C and ECOG performance status and added to traditional factors , helps predict postoperative morbidity and mortality following CS+HIPEC Background In selected patients with colorectal peritoneal carcinomatosis ( PC ) , cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemoperfusion ( HIPEC ) may improve survival . We aim ed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population . Methods Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin ( 200–460 mg/m2 ) or mitomycin C ( 35 mg/m2 ) . Postoperative outcome and long-term survival were prospect ively recorded . The impact of clinical variables on overall survival ( OS ) was assessed using univariate and Cox multivariate analysis . Results Between October 2002 and May 2012 , 166 patients were treated with CRS and HIPEC . Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients . Postoperative mortality and major morbidity were 2.4 and 35 % , respectively . Half of the patients received adjuvant chemotherapy . After a median follow-up of 18 months , OS was 27 months ( 95 % confidence interval 20.8–33.2 ) . On univariate analysis , OS was associated with extent of disease ( P < 0.001 ) , neoadjuvant chemotherapy with bevacizumab ( P = 0.021 ) , completeness of cytoreduction ( CC ) ( P < 0.001 ) , and adjuvant chemotherapy ( P = 0.04 ) , but not with primary disease site , synchronous presentation , or chemoperfusion drug . In multivariate Cox regression , independent predictors of OS were CC ( hazard ratio 0.29 , P < 0.001 ) and neoadjuvant therapy containing bevacizumab ( hazard ratio 0.31 , P = 0.019 ) . Conclusions Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab . This regimen merits prospect i ve study in patients with resectable PC of colorectal origin Background Peritoneal carcinomatosis is regarded as a common sign of advanced tumor stage , tumor progression or local recurrence of appendiceal and colorectal cancer and is generally associated with poor prognosis . Although survival of patients with advanced stage CRC has markedly improved over the last 20 years with systemic treatment , comprising combination chemotherapy + /− monoclonal antibodies , the oncological outcome —especially of the subgroup of patients with peritoneal metastases — is still unsatisfactory . In addition to systemic therapy , cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) are specific treatment options for a selected group of these patients and may provide an additional therapeutic benefit in the framework of an interdisciplinary treatment concept . Methods / design The COMBATAC trial is a prospect i ve , multicenter , open-label , single-arm , single-stage phase II trial investigating perioperative systemic polychemotherapy including cetuximab in combination with CRS and HIPEC patients with histologically proven wild-type KRAS colorectal or appendiceal adenocarcinoma and synchronous or metachronous peritoneal carcinomatosis . The planned total number of patients to be recruited is 60 . The primary endpoint is progression-free survival ( PFS ) . Secondary endpoints include overall survival ( OS ) , perioperative morbidity and treatment-associated toxicity , feasibility of the combined treatment regimen , quality of life ( QoL ) and histopathological regression after preoperative chemotherapy . Discussion The COMBATAC trial is design ed to evaluate the feasibility and efficacy of the combined multidisciplinary treatment regimen consisting of perioperative systemic combination chemotherapy plus cetuximab and CRS plus bidirectional HIPEC with intraperitoneal oxaliplatin . Trial registration Clinical Trials.gov Identifier : NCT01540344 , EudraCT number : 2009 - 014040 - The effects of vascular endothelial growth factor ( VEGF ) blockade on the vascular biology of human tumors are not known . Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion , vascular volume , microvascular density , interstitial fluid pressure and the number of viable , circulating endothelial and progenitor cells , and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients . These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors PURPOSE Three-year disease-free survival ( DFS ) was significantly improved in patients who had undergone resection with curative intent for stage II or III colon cancer who received bolus plus continuous-infusion fluorouracil plus leucovorin ( LV5FU2 ) with the addition of oxaliplatin ( FOLFOX4 ) . Final results of the study , including 6-year overall survival ( OS ) and 5-year up date d DFS , are reported . PATIENTS AND METHODS A total of 2,246 patients were r and omly assigned to receive LV5FU2 or FOLFOX4 for 6 months . The primary end point was DFS . Secondary end points were OS and safety . Results Five-year DFS rates were 73.3 % and 67.4 % in the FOLFOX4 and LV5FU2 groups , respectively ( hazard ratio [ HR ] = 0.80 ; 95 % CI , 0.68 to 0.93 ; P = .003 ) . Six-year OS rates were 78.5 % and 76.0 % in the FOLFOX4 and LV5FU2 groups , respectively ( HR = 0.84 ; 95 % CI , 0.71 to 1.00 ; P = .046 ) ; corresponding 6-year OS rates for patients with stage III disease were 72.9 % and 68.7 % , respectively ( HR = 0.80 ; 95 % CI , 0.65 to 0.97 ; P = .023 ) . No difference in OS was seen in the stage II population . The incidence of second noncolorectal cancers was 5.5 % and 6.1 % in the FOLFOX4 and LV5FU2 groups , respectively . Among patients receiving oxaliplatin , the frequency of grade 3 peripheral sensory neuropathy was 1.3 % 12 months after treatment and 0.7 % at 48 months . CONCLUSION Adding oxaliplatin to LV5FU2 significantly improved 5-year DFS and 6-year OS in the adjuvant treatment of stage II or III colon cancer and should be considered after surgery for patients with stage III disease BACKGROUND Cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) are increasingly used to treat peritoneal carcinomatosis from colorectal cancer . It is still relatively unknown which poor prognostic factors to avoid in order to optimize patient selection for CRS + HIPEC . METHODS Between February 2003 and October 2011 , 68 consecutive colorectal cancer patients who underwent CRS + HIPEC with a complete cytoreduction were identified from a prospect i ve data base .  Survival analysis was performed using the Kaplan-Meier method , with log rank testing of differences between groups . Multivariate analysis was conducted using Cox proportional hazard regression . RESULTS Median follow-up was 30.3 ( range , 2 - 88 ) months amongst survivors . Patients with a peritoneal cancer index ( PCI ) of 10 or less showed improved survival over those with a PCI of 11 or higher ( P = 0.03 ) . No difference in survival was seen for the other potentially poor prognostic variables including lymph node status , synchronous peritoneal disease , peri-operative systemic chemotherapy , and rectal cancer primary . CONCLUSIONS A low PCI was associated with improved survival .  Complete CRS + HIPEC appears to result in similar survival outcomes regardless of delivery of peri-operative systemic chemotherapy . Rectal origin , lymph node status , and synchronous peritoneal disease should not be used as an absolute exclusion criteria for CRS + HIPEC based on current data The purpose of this prospect i ve Phase II study was to analyze morbidity and mortality of cytoreductive surgery ( CRS ) and intraperitoneal hyperthermic perfusion ( IPHP ) in the treatment of peritoneal surface malignancies Background Selected patients with peritoneal carcinomatosis ( PC ) from colorectal cancer ( CRC ) benefit from cytoreductive surgery ( CRS ) combined with intraperitoneal chemoperfusion ( IPC ) . However , even after optimal cytoreduction , systemic and locoregional recurrence are common . Perioperative chemotherapy with bevacizumab ( BEV ) may improve the outcome of these patients . Methods / Design The BEV-IP study is a phase II , single-arm , open-label study aim ed at patients with colorectal or appendiceal adenocarcinoma with synchronous or metachronous PC . This study evaluates whether perioperative chemotherapy including BEV in combination with CRS and oxaliplatin-based IPC results in acceptable morbidity and mortality ( primary composite endpoint ) . Secondary endpoints are treatment completion rate , chemotherapy-related toxicity , pathological response , progression free survival , and overall survival . Discussion The BEV-IP trial is the first prospect i ve assessment of the safety and efficacy of perioperative chemotherapy combined with anti-angiogenic treatment in patients undergoing CRS and  IPC for colorectal peritoneal metastases . Trial registration Clinical Trials.gov Identifier : NCT02399410 EudraCT number : 2015 - 001187 - 19 ( registered March 9 , 2015 ) Background Cytoreductive surgery ( CRS ) and hyperthermic intraperitoneal chemoperfusion ( HIPEC ) for peritoneal carcinomatosis ( PC ) of colorectal origin increases survival ( OS ) compared to systemic chemotherapy alone . Signet ring histology demonstrates aggressive behavior with poor survival . We sought to determine whether CRS/HIPEC increases survival in this subset of patients . Methods We review ed 67 patients with PC of appendiceal ( AP , n = 37 ) or colorectal origin ( CRC , n = 30 ) with signet cell histology from a prospect i ve data base between May 2001 and August 2011 .  Survival analysis and multivariate Cox regression were used to determine prognostic factors for survival . Results Complete CRS ( CC-0/1 ) was achieved in 77 % ( CRC ) and 73 % ( AP ) of patients . Progression-free survival ( PFS ) and OS were 9 and 12 months in CRC and 12 and 21 months in AP patients . In the CRC group , univariate predictors of poor survival included female gender , age , American Society of Anesthesiologists score , preoperative albumin , completeness of cytoreduction , and morbidity . In a multivariate Cox regression model , incomplete cytoreduction ( CC-2/3 ) and female gender were joint significant predictors of poor survival . In the AP group , significant univariate predictors of poor survival included higher EBL and PCI score . In a multivariate Cox regression model , blood loss of > 500 ml and a body mass index of < 25 kg/m2 were joint significant predictors of poor survival . Conclusions AP signet cell tumors demonstrate a more favorable outcome than CRC signet cell tumors after CRC/HIPEC for carcinomatosis , suggesting an underlying difference in biology . CRS/HIPEC does not confer survival benefit in colorectal signet ring carcinomatosis unless complete cytoreduction can be achieved , whereas appendiceal signet ring carcinomatosis may benefit , regardless of resectability Background Long-term survival of patients with appendiceal or colorectal peritoneal carcinomatosis ( PC ) may be achieved by combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy ( CRS/HIPEC ) . Unfortunately , such favorable outcomes are realized in a minority of patients . Given the morbidity of the CRS/HIPEC and the uncertain role of postresection systemic therapy , it is important that prognostic factors in high- grade PC be clearly defined . Methods This single center , retrospective , cohort study examined the outcomes of CRS/HIPEC performed on patients with high- grade PC secondary to appendiceal or colorectal adenocarcinoma between 2007 and 2013 . Cox regression analysis was utilized to evaluate the association between potential prognostic factors [ age , sex , primary site , lymph node ( LN ) status , peritoneal cancer index ( PCI ) score , completeness of cytoreduction score ( CC score ) , number of visceral resections , and systemic chemotherapy ] and progression-free survival ( PFS ) . Results A total of 70 patients with high- grade appendiceal or colorectal PC underwent CRS/HIPEC during the study period ; 82.9 % underwent complete ( CC-0 ) cytoreduction with a median PFS of 9.7 months . Positive LNs at the time of CRS/HIPEC were predictors of worse PFS on univariate and multivariate analysis . No association was demonstrated between pre- or post-HIPEC  systemic chemotherapy and PFS . Conclusions High- grade PC secondary to appendiceal or colorectal adenocarcinoma can be managed with CRS/HIPEC . The number of LN metastases at the time of CRS/HIPEC is the strongest predictor of progression and must be considered when determining patient eligibility for this aggressive treatment BACKGROUND Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy ( CRS-HIPEC ) is the preferred treatment of peritoneal carcinomatosis ( PC ) of colorectal carcinoma . Patients with positive lymph node status have worse survival after CRS-HIPEC , which is probably due to higher rates of systemic failure . In this study , we analysed the effect of administration and timing of systemic chemotherapy on the outcome of lymph node positive colorectal carcinoma patients treated with CRS-HIPEC .  PATIENTS AND METHODS A prospect i ve data base was review ed to identify lymph node positive patients with PC treated with CRS-HIPEC within 1 year after primary tumour diagnosis between 2004 and 2012 . Medical history of the patients was studied for the administration of perioperative systemic chemotherapy and follow-up . Outcome parameters were progression-free survival ( PFS ) , overall survival ( OS ) and pattern of recurrence . RESULTS Seventy-three patients treated with CRS-HIPEC for PC from lymph node positive colorectal carcinoma were identified . Fourteen patients received  pre-CRS-HIPEC chemotherapy only , 32 patients underwent post-CRS-HIPEC chemotherapy only , 9 patients received chemotherapy both pre- and post-CRS-HIPEC and 16 patients did not receive any systemic chemotherapy . Of the 47 patients who did not receive pre-CRS-HIPEC chemotherapy , 11 ( 23 % ) did not receive any chemotherapy due to major postoperative complications . PFS and OS were significantly higher in patients who received systemic chemotherapy ( PFS : median 15 versus 4 months , P = 0.024 ; OS : median 30 versus 14 months , P = 0.015 ) , although this difference was attenuated after adjustment for major complications . Different chemotherapy timings did not differ significantly in either survival or recurrence patterns . CONCLUSIONS In patients with PC from lymph node positive colorectal carcinoma , perioperative systemic chemotherapy is associated with increased OS and PFS , although this difference may be partly explained by the occurrence of major postoperative complication ; with no evidence of difference in PFS , OS and systemic recurrence rate by timing of systemic chemotherapy HYPOTHESIS Certain clinicopathologic factors predict improved survival after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis . DESIGN Prospect i ve clinical trial . SETTING Surgical oncology service at a university academic hospital . PATIENTS A population of 109 consecutive patients with peritoneal carcinomatosis treated between December 1991 and November 1997 . INTERVENTION All patients underwent resection of gross disease followed by 2-hour intraoperative perfusion of mitomycin C ( 20 - 40 mg ) into the peritoneal cavity at a temperature of 40.5 degrees C. MAIN OUTCOME MEASURES Clinicopathologic factors that independently predicted improved overall survival rates . RESULTS Overall survival at 1 and 3 years was 61 % and 33 % , respectively . With median follow-up of 52 months , median overall survival was 16 months . Four factors were significant independent predictors of improved survival by multivariate analysis : nonadenocarcinoma histologic features ( P = .001 ) , the appendix as a primary site ( P = .003 ) , the absence of hepatic parenchymal metastases ( P = .01 ) , and complete resection of all gross disease ( R1/0 resection ) ( P<.001 ) . Patients with an R1/0 resection vs an incomplete resection of gross disease ( R2 resection ) had 3-year overall survival of 68 % vs 21 % ( P<.001 ) . CONCLUSIONS Patients with peritoneal carcinomatosis have a uniformly poor prognosis . However , in select patients , the natural history of this disease condition may be altered by using the multimodality approach of cytoreductive surgery and intraperitoneal hyperthermic chemotherapy . These results require confirmation in prospect i ve r and omized studies PURPOSE Symptoms and complications of metastatic colorectal cancer ( mCRC ) differ by metastatic sites . There is a paucity of prospect i ve survival data for patients with peritoneal carcinomatosis colorectal cancer ( pcCRC ) . We characterized outcomes of patients with pcCRC enrolled onto two prospect i ve r and omized trials of  chemotherapy and contrasted that with other manifestations of mCRC ( non-pcCRC ) . METHODS A total of 2,095 patients enrolled onto two prospect i ve r and omized trials were evaluated for  overall survival ( OS ) and progression-free survival ( PFS ) . A Cox proportional hazard model was used to assess the adjusted associations . RESULTS The characteristics of the pcCRC group ( n = 364 ) were similar to those of the non-pcCRC patients in median age ( 63 v 61 years , P = .23 ) , sex ( 57 % males v 61 % , P = .23 ) , and performance status ( Eastern Cooperative Oncology Group performance status 0 or 1 94 % v 96 % , P = .06 ) , but differed in frequency of liver ( 63 % v 82 % , P < .001 ) and lung metastases ( 27 % v 34 % , P = .01 ) . Median OS ( 12.7 v 17.6 months , hazard ratio [ HR ] = 1.3 ; 95 % CI , 1.2 to 1.5 ; P < .001 ) and PFS ( 5.8 v 7.2 months , HR = 1.2 ; 95 % CI , 1.1 to 1.3 ; P = .001 ) were shorter for pcCRC versus non-pcCRC . The unfavorable prognostic influence of pcCRC remained after adjusting for age , PS , liver metastases , and other factors ( OS : HR = 1.3 , P < .001 ; PFS : HR = 1.1 , P = .02 ) . Infusional fluorouracil , leucovorin , and oxaliplatin was superior to irinotecan , leucovorin , and fluorouracil as a first-line treatment among pcCRC ( HR for OS = 0.62 , P = .005 ) and non-pcCRC patients ( HR = 0.66 , P < .001 ) . CONCLUSION pcCRC is associated with a significantly shorter OS and PFS as compared with other manifestations of mCRC . Future trials for mCRC should consider stratifying on the basis of pcCRC status Abstract Introduction Intraperitoneal ( IP ) vascular endothelial growth factor ( VEGF ) levels have been shown to vary in the peritoneal cavity of patients with peritoneal surface malignancies . Our purpose was to correlate levels of IP VEGF with overall and disease-free survival to identify whether IP VEGF can be used to prognosticate patients and the possible role of IP bevacizumab . Methods From February to October 2012 , 97 consecutive patients with peritoneal carcinomatosis were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy . Intravenous ( IV ) VEGF levels were taken before surgery , whereas IP VEGF levels were taken at various time points during and after surgery . Results Median follow-up was 19.48 months . On univariate analysis , a lower IP VEGF taken just after incision ( T1 ) was associated with improved overall ( P = 0.0004 ) and disease-free survival ( P = 0.0006 ) at 2 years . A lower T1/IV VEGF ratio also was associated with improved overall ( P = 0.004 ) and disease-free survival ( P = 0.0051 ) . On multivariate analysis , a lower T1 was associated with improved overall survival , whereas a lower T1/IV VEGF was associated with improved disease-free survival . On subset analysis , these two variables were associated with improved survival in colorectal cancers . Conclusions A lower IP VEGF level prior to surgery is associated with improved survival . The use of preoperative intraperitoneal bevacizumab for patients with a heavy disease load should be considered , especially in colorectal cancers 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 Background : Although a r and omized trial demonstrated a survival benefit of cytoreductive surgery ( CRS ) and intraperitoneal chemotherapy ( IPC ) over systemic chemotherapy alone , the treatment of peritoneal carcinomatosis from colorectal cancer ( CRPC ) is still a matter of debate . The aims of this study were to evaluate long-term outcome after CRS and IPC and to identify the prognostic factors associated with a cure . Methods : Patients were considered cured if the disease-free survival interval lasted at least 5 years after the treatment of CRPC or its last recurrence . Patients who had died postoperatively , or from non – cancer-related deaths , or patients with a follow-up of less than 5 years since the last curative treatment were excluded from the analysis . Results : From 1995 to 2006 , 107 patients ( median age , 48 years ; range , 19–67 years ) underwent complete CRS , followed by IPC .  Postoperative complications occurred in 50 patients ( 53 % ) , including 4 postoperative deaths . After a median follow-up of 77 months ( range , 60–144 months ) , 5-year and 10-year overall survival rates were 35 % and 15 % , respectively . Seventeen patients ( 16 % ) were considered cured after a disease-free interval of at least 5 years , of whom 14 never developed a recurrence . Cured patients had a significantly lower median peritoneal cancer index than noncured patients , respectively 4 ( 3–16 ) and 12 ( 2–36 ) ( P = 0.0002 ) . In multivariate analysis , a peritoneal cancer index of 10 or less was the only independent factor predicting cure . Conclusions : The cure rate ( 16 % ) after complete CRS of colorectal peritoneal carcinomatosis , followed by IPC , in selected patients is close to that obtained after resection of colorectal liver metastases Background : Cytoreductive surgery ( CS ) and intraperitoneal hyperthermic chemotherapy ( IPHC ) are efficacious in patients with disseminated mucinous tumors of the appendix . We review ed our experience using this approach for nonappendiceal colorectal cancer ( NACC ) . Methods : We performed a retrospective chart review of a prospect i ve data base for patients undergoing CS and IPHC with mitomycin C for peritoneal carcinomatosis from colorectal primary lesions between December 1991 and April 2002 . Results : There were 77 patients , with a median age of 54 years . Peritoneal carcinomatosis was synchronous and metachronous in 27 % and 73 % patients , respectively . Seventy-five percent of patients ( n = 58 ) had received chemotherapy prior to IPHC .  Complete resection of all gross disease was accomplished in 37 patients ( 48 % ) . The mean carcinoembryonic antigen level decreased from a preoperative value of 31.2 to a postoperative value of 6.9 ( P < .0001 ) . Overall survival ( OS ) at 1 , 3 , and 5 years was 56 % , 25 % , and 17 % , respectively . With a median follow-up of 15 months , the median OS was 16 months . Perioperative morbidity and mortality were 30 % and 12 % , respectively . Hematologic toxicity occurred in 15 patients ( 19 % ) . Cox regression analysis identified poor performance status ( P = .018 ) , bowel obstruction ( P = .001 ) , malignant ascites ( P = .001 ) , and incomplete resection of gross disease ( P = .011 ) as independent predictors of decreased survival . Patients with complete resection of all gross disease had a 5-year OS of 34 % , with a median OS of 28 months . Conclusions : CS and IPHC with mitomycin C can improve outcomes for select patients with peritoneal spread from NACC . One third of patients who undergo complete resection of gross disease have long-term survival AIMS The purpose of this phase II study was to analyze the morbidity and mortality of cytoreductive surgery ( CRS ) + intraperitoneal hyperthermic perfusion ( IPHP ) in the treatment of peritoneal surface malignancies . PATIENTS AND METHODS One hundred and sixty four patients ( 36 ovarian cancer , 32 abdominal sarcomatosis , 34 peritoneal mesothelioma , 36 pseudomyxoma peritonei , 12 gastric cancer , 8 colon adenocarcinoma and 8 from other origins ) underwent 166 procedures . Two patients underwent the intervention twice due to disease relapse . The mean follow-up was 20.6 months ( range : 0.4 - 91.3 ) . The mean age was 52 years ( range : 24 - 76 ) .  CRS was performed with peritonectomy procedures . IPHP through Closed abdominal technique was conducted with preheated ( 42.5 degrees ) perfusate containing cisplatin+mitomycin C or cisplatin+doxorubicin for 60/90 minutes . RESULTS grade 3/4 morbidity rate was 12.0 % . Some frequent post-operatory complications were intestinal fistulas ( 17 ) , respiratory ( 5 ) and abdominal bleeding ( 4 ) . Multivariate analysis with logistic regression model with the backward elimination method identified carcinomatosis extension ( OR : 5.3 , CI95 % : 1.2 - 24.5 ) as the best predictor of morbidity grade 3/4 . Four patients presented grade 3/4 toxicity . Operative mortality rate was 0.6 % . CONCLUSIONS CRS+ IPHP presented acceptable morbidity 3/4 toxicity and mortality rates what support the need to be tested in prospect i ve phase III clinical trial PURPOSE We investigated the safety and pharmacokinetics of a recombinant human monoclonal antibody to vascular endothelial growth factor ( rhuMAb VEGF ) in patients with cancer . PATIENTS AND METHODS Cohorts of patients with metastatic cancer having failed prior therapy entered a phase I trial of rhuMAb VEGF administered by a 90-minute intravenous infusion at doses from 0.1 to 10.0 mg/kg on days 0 , 28 , 35 , and 42 . Patients underwent pharmacokinetic sampling on day 0 and had serum sample s obtained during the subsequent 28 days . Response assessment was carried out on days 49 and 72 . RESULTS Twenty-five patients with a median Eastern Cooperative Oncology Group performance status of 0 were accrued . There were no grade III or IV adverse events definitely related to the antibody . There were three episodes of tumor-related bleeding . Infusions of rhuMAb VEGF were well tolerated without significant toxicity . Grade s I and II adverse events possibly or probably related to study drug included asthenia , headache , and nausea . Pharmacokinetics revealed a linear profile with a half-life of 21 days . There were no objective responses , though 12 patients experienced stable disease over the duration of the study . CONCLUSION rhuMAb VEGF was safely administered without dose-limiting toxicity at doses ranging up to 10 mg/kg . Multiple doses of rhuMAb VEGF were well tolerated , and pharmacokinetic studies indicate that doses of > or = 0.3 mg/kg have a half-life similar to that of other humanized antibodies . Subsequent trials will explore rhuMAb VEGF alone and in combination chemotherapy Objective : To assess the influence of parietal and visceral peritonectomy procedures on moderate/severe morbidity in patients undergoing surgical cytoreducion and hyperthermic intraperitoneal chemotherapy ( HIPEC )  and to identify subgroups of patients at highest operative risk . Background : Cytoreducion with HIPEC is an effective but potentially morbid treatment option for peritoneal surface malignancies . Although complication rates have recently decreased with increasing experience , risk-factors for adverse operative outcome are still poorly understood . Methods : A prospect i ve data base of 426 combined procedures was review ed . Multivariate analysis tested the correlation between major morbidity and 6 peritonectomies ( greater and lesser omentectomy , pelvic , parietal anterior , left and right diaphragmatic peritonectomy ) , 14 visceral resections , 5 other operative factors , and 12 clinical variables . The extent of peritoneal involvement was quantified by peritoneal cancer index ( PCI ) . Results : Mortality and major morbidity were 2.6 % and 28.2 % . PCI , number of visceral resections , poor performance status , and cisplatin dose more than 240 mg independently correlated to morbidity . The type and number of parietal peritonectomies and the type of visceral resections did not correlated to complications . Major morbidity rate was 65.7 % in 35 ( 8.2 % ) patients with at least 2 of the following factors : PCI greater than 30 , more than 5 visceral resections , poor  performance status . Morbidity was 100 % in 9 patients presenting all the risk factors . Conclusions : Acceptable morbidity and low mortality may be achieved in high-volume centers . Operative outcome is mainly affected by a complex interplay of tumor , patient , and treatment-related factors . Preoperative and early intraoperative assessment of operative risk may identify a subset of patients unlikely to tolerate aggressive management PURPOSE To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis ( PC ) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy ( HIPEC ) . PATIENTS AND METHODS All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated . The st and ard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period , but who had not benefited from HIPEC because the technique was unavailable in the center at that time . RESULTS Forty-eight patients were retrospectively included in the st and ard group and were compared with 48 patients who had undergone HIPEC  and were evaluated prospect ively . All characteristics were comparable except age and tumor differentiation . There was no difference in systemic chemotherapy , with a mean of 2.3 lines per patient . Median follow-up was 95.7 months in the st and ard group versus 63 months in the HIPEC group . Two-year and 5-year overall survival rates were 81 % and 51 % for the HIPEC group , respectively , and 65 % and 13 % for the st and ard group , respectively . Median survival was 23.9 months in the st and ard group versus 62.7 months in the HIPEC group ( P < .05 , log-rank test ) . CONCLUSION Patients with isolated , resectable PC achieve a median survival of 24 months with modern chemotherapies , but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months , with a 5-year survival rate of 51 % INTRODUCTION Vascular endothelial growth factor ( VEGF ) is one of the most important angiogenic factors in solid tumours and plays an important role in ascites development in peritoneal surface malignancies ( PSM ) . The main goal of this study was to determine the evolution and factors influencing intraperitoneal ( IP ) VEGF burden during cytoreductive surgery ( CRS ) with curative intent . PATIENTS AND METHODS Ninety-seven consecutive patients with PSM were treated with CRS at a single centre with curative intent . Patient data were collected prospect ively between February 2012 and October 2012 . An enzyme-linked immunosorbent assay technique was used to assess  VEGF levels in intravenous ( IV ) systemic blood sample s before incision and after abdominal closure , and in IP sample s during abdominal cavity exploration , after completion of CRS , after hyperthermic IP chemotherapy , and at 1 and 24h after abdominal closure . RESULTS The IP VEGF burden increased significantly after CRS , and then decreased progressively ( p<0.005 ) . In multivariate analysis , neoadjuvant IV bevacizumab significantly decreased the preoperative IP VEGF burden , tumour load according to Peritoneal Cancer Index value increased significantly the preoperative IP VEGF burden and a low preoperative IP VEGF burden was associated with significantly increased postoperative complications . Neoadjuvant IV bevacizumab is the only factor that influences the preoperative IV VEGF concentration . CONCLUSION For patients with PSM who were treated with curative intent , the IP VEGF burden increased after CRS , and was reduced prior to surgery by the administration of neoadjuvant IV bevacizumab The incidence of infectious complications due to several contributory causes is particularly elevated and life-threatening in patients undergoing peritonectomy and HIPEC procedure for peritoneal carcinomatosis . Following a previous experience , we started a prospect i ve protocol study of preoperative screening , perioperative prophylaxis and postoperative surveillance and treatment . A total of 111 patients with peritoneal carcinomatosis of various origin underwent CRS with HIPEC between April 2004 and December 2012 . The group was divided into a pilot group of 30 patients ( 04/04 to 05/08 ) and a main group of 81 patients ( 06/08 to 12/12 ) . Overall postoperative morbidity rate was 44 % , with 35.8 % of symptomatic infections . No post-operative mortality was observed . Microorganisms were isolated in 24 patients ( 80.0 % ) in the first group and 54 ( 66.7 % ) in the second . They were symptomatic in 18 cases ( 75.0 % ) and 25 ( 46.3 % ) cases respectively . In addition , 7 invasive c and idosis were recorded ( 25.9 % ) . Colon resection ( P = 0.01 ) and duration of surgery ( P = 0.0008 ) were associated with infection at logistic regression model . Concerning symptomatic infections , only Infection Risk Index ( P = 0.009 ) showed significance at multivariate analysis . Despite a significant incidence of infectious complications , establishment of a prevention , surveillance and treatment protocol lead to a zero mortality rate in the observed patients of our experience . Owing to the obtained results , we suggest the use of a st and ardized protocol for the prevention , monitoring and treatment in all patients enrolled for cytoreductive surgery and HIPEC
BACKGROUND / PURPOSE Despite its widespread use , no r and omised studies have investigated the value of perioperative systemic therapy as adjunct to cytoreduction and HIPEC for colorectal peritoneal metastases .
This systematic review evaluated the available evidence , which consists of non-r and omised studies only .