human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Introduction The treatment of peritoneal carcinomatosis is based on cytoreduction followed by hyperthermic intraperitoneal chemotherapy and combined with adjuvant chemotherapy . In 2003 , a r and omized trial was finished comparing systemic chemotherapy alone with cytoreduction followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy . This trial showed a positive result favoring the studied treatment . This trial has now been up date d to a minimal follow-up of 6 years to show long-term results . Patients and Methods For all patients still alive , the follow-up was up date d until 2007 . In the original study , four patients were excluded — two because of no eligible histology/pathology and two because of major protocol violations . After r and omization , four patients in the HIPEC arm and six in the control arm were not treated using the intended therapy , one patient because of withdrawal , one because of a life-threatening other malignant disease and the others because of progressive disease before initiation of the treatment . During the follow-up , one patient was crossed over from the control arm and underwent cytoreduction and HIPEC for recurrent disease , after the assigned treatment was completed . The data from these patients were censored at the moment of the cross-over . Progression-free and disease-specific survival were analyzed using the Kaplan Meyer test and compared using the log rank method . The long-term results were studied in more detail to evaluate efficacy and toxicity . Results At the time of this up date , the median follow-up was almost 8 years ( range 72–115 months ) . In the st and ard arm , 4 patients were still alive , 2 with and 2 without disease ; in the “ HIPEC ’ arm , 5 patients were still alive , 2 with and 3 without disease . The median progression-free survival was 7.7 months in the control arm and 12.6 months in the HIPEC arm ( P = 0.020 ) . The median disease-specific survival was 12.6 months in the control arm and 22.2 months in the HIPEC arm ( P = 0.028 ) . The 5-year survival was 45 % for those patients in whom a R1 resection was achieved . Conclusion With 90 % of all events having taken place up to this time , this r and omized trial shows that cytoreduction followed by HIPEC does significantly add survival time to patients affected by peritoneal carcinomatosis of colorectal origin . For a selected group , there is a possibility of long-term survival Background Cytoreductive surgery ( CS ) combined with hyperthermic intraperitoneal chemotherapy ( HIPEC ) for treatment of peritoneal carcinomatosis ( PC ) traditionally involves high perioperative morbidity and mortality . We report our experience performing CS-HIPEC in a high-volume regional perfusion program design ed to limit morbidity and mortality . Methods A total of 122 patients underwent 124 CS-HIPEC procedures . Common tumors treated with CS-HIPEC included appendiceal ( 38.5 % ) , colorectal ( 24.6 % ) , and ovarian cancers ( 13.1 % ) , and peritoneal mesothelioma ( 12.3 % ) . Complete cytoreduction was performed in all patients , with organ resections performed as necessary . Results R0 resection was achieved in 28.7 % of cases , R1 in 54.9 % , and R2 in 16.4 % . Median operative time was 460 minutes ( range , 250–840 minutes ) , and median blood loss was 1150 mL ( range , 10–14,000 mL ) . Median hospital and intensive care unit stays were 12 days ( range , 6–50 days ) and 3 days ( range , 0–41 days ) , respectively . Grade 3 or 4 morbidity by National Cancer Institute criteria ( major morbidity ) was seen in 29.8 % of cases , with overall morbidity 56.5 % . Independent prognostic variables for major morbidity included number of anastomoses and degree of cytoreduction . In-hospital and 30-day mortality rates were 0 % and 1.6 % , respectively . The most favorable diagnosis was appendiceal cancer , for which 2-year survival was 66.7 % , with lower- grade histologic subtypes of appendiceal cancer reaching 85.7 % 2-year survival . Colorectal cancer had 2-year survival of 36.7 % . Conclusions In a high-volume center with extensive experience treating peritoneal malignancies , perioperative mortality can be lowered to nearly zero , although morbidity remains high . CS-HIPEC procedures should be studied further in a controlled manner to help define their important role in the care of patients with PC No new chemotherapy agents have been developed recently that present hope for improving survival in patients with colon or rectal cancer . We undertook this study to investigate a new route of administering an old drug , 5-fluorouracil ( 5-FU ) .  Sixty-six patients with advanced primary colon or rectal cancer were r and omized to receive 12 cycles with increasing dosages of intravenous ( IV ) or intraperitoneal ( IP ) 5-FU ; the mean follow-up time was three years . The maximal tolerable dose and objective adverse side effects were prospect ively recorded . The mean daily dose of 5-FU given by the IV route was 904 mg ; for the IP route it was 1361 mg ( p2 less than 0.0001 ) . Two of ten patients had recurrent peritoneal carcinomatosis when treated with IP 5-FU ; ten of eleven patients treated with IV 5-FU developed peritoneal implants ( p2 less than 0.003 ) . The incidence of serious complications was the same , but hematologic toxicity and hepatic toxicity were significantly reduced in patients who received IP 5-FU . When 5-FU is delivered by the IP route , the tolerable dose of drug was markedly increased without an increase in adverse side effects . The natural history of surgically treated disease was changed by reducing the incidence of peritoneal carcinomatosis but time to relapse and survival was not improved . IP 5-FU may be recommended for investigation in patients with perforated colon cancer , peritoneal implants , or as one part of a multimodality treatment protocol for colorectal cancer . If 5-FU is given to patients with gastrointestinal malignancy , the IP route should be strongly considered Background : Recent therapeutic developments dem and for an up date of information on natural history , risk factors and prognosis of peritoneal carcinomatosis ( PC ) of colorectal origin . Therefore , prospect i ve registry data should provide information about incidence , predictors and outcome . Methods : From a prospect ively exp and ed single-institutional data base with 2406 consecutive patients with colorectal cancer ( CRC ) , clinical , histological and survival data were analysed for independent risk factors and prognosis . Findings were then stratified to the era of treatment without chemotherapy , 5-Fluorouracil-only and contemporary systemic chemotherapy , respectively . Results : Overall , 256 ( 10.6 % ) patients were diagnosed with PC thereof 141 ( 5.85 % ) with metachronous PC . Independent risk factors for the development of metachronous PC were age < 62 years , N2-status , T4-status , location of the primary in the left colon or appendix . In the era of contemporary systemic chemotherapy , prognosis for PC improved only not-significantly ( median survival of 17.9 months vs 7.03 months , P=0.054 ) . Conclusion : Despite improvement in the overall outcome with prolonged median survival for the complete patient cohort with CRC , those patients with PC have not experienced the same benefit . In the era of contemporary systemic chemotherapy , progress in treatment result ed in only limited survival benefit . Thus , continuous efforts for further therapeutic advancements should be undertaken in these patients diagnosed with PC 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 Purpose This nationwide study evaluated results of cytoreductive surgery ( CRS ) combined with hyperthermic intraperitoneal chemotherapy ( HIPEC ) for peritoneal metastasis of colorectal origin in the Netherl and s following a national protocol . Methods In a multi-institutional study prospect i ve data bases of patients with peritoneal carcinomatosis ( PC ) from colorectal cancer and pseudomyxoma peritonei ( PMP ) treated according to the Dutch HIPEC protocol , a uniform approach for the CRS and HIPEC treatment , were review ed . Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival . Results Nine-hundred sixty patients were included ; 660 patients ( 69 % ) were affected by PC of colorectal carcinoma and the remaining suffered from PMP ( 31 % ) . In 767 procedures ( 80 % ) , macroscopic complete cytoreduction was achieved . Three-hundred and thirty one patients had grade III – V complications ( 34 % ) . Thirty-two patients died perioperatively ( 3 % ) . Median length of hospital stay was 16 days ( range 0–166 days ) . Median follow-up period was 41 months ( 95 % confidence interval ( CI ) , 36–46 months ) . Median progression-free survival was 15 months ( 95 % CI 13–17 months ) for CRC patients and 53 months ( 95 % CI 40–66 months ) for PMP patients . Overall median survival was 33 ( 95 % CI 28–38 months ) months for CRC patients and 130 months ( 95 % CI 98–162 months ) for PMP patients . Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients . Conclusions The results underline the safety and efficacy of cyt 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Introduction The treatment of peritoneal carcinomatosis is based on cytoreduction followed by hyperthermic intraperitoneal chemotherapy and combined with adjuvant chemotherapy . In 2003 , a r and omized trial was finished comparing systemic chemotherapy alone with cytoreduction followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy . This trial showed a positive result favoring the studied treatment . This trial has now been up date d to a minimal follow-up of 6 years to show long-term results . Patients and Methods For all patients still alive , the follow-up was up date d until 2007 . In the original study , four patients were excluded — two because of no eligible histology/pathology and two because of major protocol violations . After r and omization , four patients in the HIPEC arm and six in the control arm were not treated using the intended therapy , one patient because of withdrawal , one because of a life-threatening other malignant disease and the others because of progressive disease before initiation of the treatment . During the follow-up , one patient was crossed over from the control arm and underwent cytoreduction and HIPEC for recurrent disease , after the assigned treatment was completed . The data from these patients were censored at the moment of the cross-over . Progression-free and disease-specific survival were analyzed using the Kaplan Meyer test and compared using the log rank method . The long-term results were studied in more detail to evaluate efficacy and toxicity . Results At the time of this up date , the median follow-up was almost 8 years ( range 72–115 months ) . In the st and ard arm , 4 patients were still alive , 2 with and 2 without disease ; in the “ HIPEC ’ arm , 5 patients were still alive , 2 with and 3 without disease . The median progression-free survival was 7.7 months in the control arm and 12.6 months in the HIPEC arm ( P = 0.020 ) . The median disease-specific survival was 12.6 months in the control arm and 22.2 months in the HIPEC arm ( P = 0.028 ) . The 5-year survival was 45 % for those patients in whom a R1 resection was achieved . Conclusion With 90 % of all events having taken place up to this time , this r and omized trial shows that cytoreduction followed by HIPEC does significantly add survival time to patients affected by peritoneal carcinomatosis of colorectal origin . For a selected group , there is a possibility of long-term survival Background Cytoreductive surgery ( CS ) combined with hyperthermic intraperitoneal chemotherapy ( HIPEC ) for treatment of peritoneal carcinomatosis ( PC ) traditionally involves high perioperative morbidity and mortality . We report our experience performing CS-HIPEC in a high-volume regional perfusion program design ed to limit morbidity and mortality . Methods A total of 122 patients underwent 124 CS-HIPEC procedures . Common tumors treated with CS-HIPEC included appendiceal ( 38.5 % ) , colorectal ( 24.6 % ) , and ovarian cancers ( 13.1 % ) , and peritoneal mesothelioma ( 12.3 % ) . Complete cytoreduction was performed in all patients , with organ resections performed as necessary . Results R0 resection was achieved in 28.7 % of cases , R1 in 54.9 % , and R2 in 16.4 % . Median operative time was 460 minutes ( range , 250–840 minutes ) , and median blood loss was 1150 mL ( range , 10–14,000 mL ) . Median hospital and intensive care unit stays were 12 days ( range , 6–50 days ) and 3 days ( range , 0–41 days ) , respectively . Grade 3 or 4 morbidity by National Cancer Institute criteria ( major morbidity ) was seen in 29.8 % of cases , with overall morbidity 56.5 % . Independent prognostic variables for major morbidity included number of anastomoses and degree of cytoreduction . In-hospital and 30-day mortality rates were 0 % and 1.6 % , respectively . The most favorable diagnosis was appendiceal cancer , for which 2-year survival was 66.7 % , with lower- grade histologic subtypes of appendiceal cancer reaching 85.7 % 2-year survival . Colorectal cancer had 2-year survival of 36.7 % . Conclusions In a high-volume center with extensive experience treating peritoneal malignancies , perioperative mortality can be lowered to nearly zero , although morbidity remains high . CS-HIPEC procedures should be studied further in a controlled manner to help define their important role in the care of patients with PC No new chemotherapy agents have been developed recently that present hope for improving survival in patients with colon or rectal cancer . We undertook this study to investigate a new route of administering an old drug , 5-fluorouracil ( 5-FU ) .  Sixty-six patients with advanced primary colon or rectal cancer were r and omized to receive 12 cycles with increasing dosages of intravenous ( IV ) or intraperitoneal ( IP ) 5-FU ; the mean follow-up time was three years . The maximal tolerable dose and objective adverse side effects were prospect ively recorded . The mean daily dose of 5-FU given by the IV route was 904 mg ; for the IP route it was 1361 mg ( p2 less than 0.0001 ) . Two of ten patients had recurrent peritoneal carcinomatosis when treated with IP 5-FU ; ten of eleven patients treated with IV 5-FU developed peritoneal implants ( p2 less than 0.003 ) . The incidence of serious complications was the same , but hematologic toxicity and hepatic toxicity were significantly reduced in patients who received IP 5-FU . When 5-FU is delivered by the IP route , the tolerable dose of drug was markedly increased without an increase in adverse side effects . The natural history of surgically treated disease was changed by reducing the incidence of peritoneal carcinomatosis but time to relapse and survival was not improved . IP 5-FU may be recommended for investigation in patients with perforated colon cancer , peritoneal implants , or as one part of a multimodality treatment protocol for colorectal cancer . If 5-FU is given to patients with gastrointestinal malignancy , the IP route should be strongly considered Background : Recent therapeutic developments dem and for an up date of information on natural history , risk factors and prognosis of peritoneal carcinomatosis ( PC ) of colorectal origin . Therefore , prospect i ve registry data should provide information about incidence , predictors and outcome . Methods : From a prospect ively exp and ed single-institutional data base with 2406 consecutive patients with colorectal cancer ( CRC ) , clinical , histological and survival data were analysed for independent risk factors and prognosis . Findings were then stratified to the era of treatment without chemotherapy , 5-Fluorouracil-only and contemporary systemic chemotherapy , respectively . Results : Overall , 256 ( 10.6 % ) patients were diagnosed with PC thereof 141 ( 5.85 % ) with metachronous PC . Independent risk factors for the development of metachronous PC were age < 62 years , N2-status , T4-status , location of the primary in the left colon or appendix . In the era of contemporary systemic chemotherapy , prognosis for PC improved only not-significantly ( median survival of 17.9 months vs 7.03 months , P=0.054 ) . Conclusion : Despite improvement in the overall outcome with prolonged median survival for the complete patient cohort with CRC , those patients with PC have not experienced the same benefit . In the era of contemporary systemic chemotherapy , progress in treatment result ed in only limited survival benefit . Thus , continuous efforts for further therapeutic advancements should be undertaken in these patients diagnosed with PC 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 Purpose This nationwide study evaluated results of cytoreductive surgery ( CRS ) combined with hyperthermic intraperitoneal chemotherapy ( HIPEC ) for peritoneal metastasis of colorectal origin in the Netherl and s following a national protocol . Methods In a multi-institutional study prospect i ve data bases of patients with peritoneal carcinomatosis ( PC ) from colorectal cancer and pseudomyxoma peritonei ( PMP ) treated according to the Dutch HIPEC protocol , a uniform approach for the CRS and HIPEC treatment , were review ed . Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival . Results Nine-hundred sixty patients were included ; 660 patients ( 69 % ) were affected by PC of colorectal carcinoma and the remaining suffered from PMP ( 31 % ) . In 767 procedures ( 80 % ) , macroscopic complete cytoreduction was achieved . Three-hundred and thirty one patients had grade III – V complications ( 34 % ) . Thirty-two patients died perioperatively ( 3 % ) . Median length of hospital stay was 16 days ( range 0–166 days ) . Median follow-up period was 41 months ( 95 % confidence interval ( CI ) , 36–46 months ) . Median progression-free survival was 15 months ( 95 % CI 13–17 months ) for CRC patients and 53 months ( 95 % CI 40–66 months ) for PMP patients . Overall median survival was 33 ( 95 % CI 28–38 months ) months for CRC patients and 130 months ( 95 % CI 98–162 months ) for PMP patients . Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients . Conclusions The results underline the safety and efficacy of cyt 
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