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: Fifty patients were r and omized to receive adjuvant intraperitoneal 5-fluorouracil ( 5-FU , 500 mg/m2/day ) and intravenous leucovorin ( 60 mg/m2/day ) and 51 to receive placebo after curative surgery for colorectal cancer . Treatment started on the day after surgery and continued for 6 days . One case of stomatitis , one of leucopenia and one case of abnormal liver function tests were the only chemotherapy-related toxic effects . From the second day of treatment , pain during intraperitoneal infusions occurred more frequently in the 5-FU group , although statistical significance was only attained on day 2 ( P<0.05 ) . The groups did not differ substantially regarding any other adverse effects , the incidence of surgical complications , second laparotomies , time from surgery to discharge , or premature treatment terminations . The postoperative course after intraperitoneal 5-FU and intravenous leucovorin was thus not more complicated than that in patients treated with placebo . The tolerance was acceptable and chemotherapy-related toxicity was rare . Thus important prerequisites exist for more widespread use of the present regimen in order to evaluate its impact on survival . RésuméCent un patients ont été r and omisés après traitement chirurgical curatif d'un cancer colorectal ; 50 patients ont reçu un traitement adjuvant intrapéritional de 5-FU ( 500 mg/m2/jour ) et intraveineux de Leucovorine ( 60 mg/m2/jour ) et 51 patients ont reçu un  placebo .  Le traitement a été instauré le 1er jour postopératoire et poursuivi durant 6 jours . Les seuls troubles consécutifs à la chimiothérapie observés ont été : 1 cas de stomatite , 1 cas de leucopénie et 1 cas de perturbation des tests hépatiques . A partir du 2ème jour de traitement , des douleurs intraperitionales surviennent plus fréquemment après l'infusion de 5FU bien que la différence ne soit statistiquement significative que pour le 2ème jour ( P<0,05 ) . Les groupes ne différent pas de manière significative quant à d'autres effets secondaires : incidence de complications chirurgicales , taux de relaparotomies , durée des séjours hospitaliers , interruption prématurée du traitement . Les suites postopératoires après injection intrapéritionale de 5FU et intraveineuse de Leucovorine ne sont pas plus compliquées qu'après l'administration d'un placebo . La tolérance est acceptable et la toxicité due à la chimiothérapie est rare . Ainsi , les bases sont établies pour un emploi plus extensif de cette combinaison chimiothérapique dans le but d'établir l'impact sur le taux de survie Background The peritoneum is the second most common site of recurrence in colorectal cancer . Early detection of peritoneal carcinomatosis ( PC ) by imaging is difficult . Patients eventually presenting with clinical ly apparent PC have a poor prognosis . Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited . Only a quarter of patients are eligible for curative treatment , consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy ( CR/HIPEC ) . However , the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate . These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases . Adjuvant hyperthermic intraperitoneal chemotherapy ( HIPEC ) seems to be suitable for this purpose . Without the need for cytoreductive surgery , adjuvant HIPEC can be performed with a low complication rate and short hospital stay . Methods / Design The aim of this study is to determine the effectiveness of  adjuvant HIPEC  in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence . This study will be performed in the nine Dutch HIPEC centres , starting in April 2015 . Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer . After resection of the primary tumour , 176 patients will be r and omized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm , or to systemic chemotherapy only in the control arm . Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection . Oxaliplatin will be used as chemotherapeutic agent , for 30 min at 42 - 43 ° C . Just before HIPEC , 5-fluorouracil and leucovorin will be administered intravenously . Primary endpoint is peritoneal disease-free survival at 18 months . Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA . Discussion Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 % . This reduction is likely to translate into a prolonged overall survival . Trial registration numberNCT02231086 ( Clinical trials.gov Objective : The aim of this prospect i ve study was to analyze the impact of second-look surgery in an attempt to treat peritoneal carcinomatosis ( PC ) at an early stage in a series of patients at high risk of developing PC from colorectal cancer . Background : The prognosis of colorectal PC has recently been improved with hyperthermic intraperitoneal chemotherapy ( HIPEC ) after complete cytoreductive surgery ( CCRS ) , and could be further improved if PC could be treated at an early stage . But , currently , the diagnosis of early PC is not accessible to imaging . Patients and Methods : From 1999 to 2006 , 29 patients without any sign of recurrence on imaging studies underwent second-look surgery 13 months after resection of the primary tumor . Patients were selected according to primary tumor-associated criteria : resected minimal synchronous macroscopic PC ( n = 16 ) , synchronous ovarian metastases ( n = 4 ) , perforated primary tumor ( n = 9 ) . Results : PC was found and treated with CCRS plus HIPEC in 16 of 29 ( 55 % ) cases , corresponding to 10 of 16 patients with initial PC , 3 of 4 patients with synchronous ovarian metastases and 3 of 9 patients with a perforated primary tumor . There was no postoperative mortality , and morbidity ( grade III/IV ) occurred in 14 % of cases . After a median follow-up of 27 months ( range , 6–96 ) , 8 of 16 patients treated with CCRS and HIPEC are free of disease , 4 relapsed in the peritoneum , and 4 developed isolated visceral metastases . Conclusion : Performing second-look surgery at 1 year in selected patients at high risk of developing PC allowed the early detection and treatment of PC in 55 % of cases . Our preliminary results have encouraged us to pursue this strategy and to evaluate it in a prospect i ve multicenter trial BACKGROUND / AIMS The benefits of adjuvant chemotherapy for colorectal cancer has been well accepted over the last decade . Published data so far has been focused in the direction of giving the right chemotherapy dose , schedule , and combinations , in order to increase the efficacy and decrease the toxicity . METHODOLOGY Eighty-seven patients with histological proved stage III rectal carcinoma were subjected to a combined adjuvant modality using laparoscopic heperthermic endoperitoneal chemotherapy ( HIPEC ) and systemic chemotherapy twenty days following the initial surgery . RESULTS Seventy patients who completed a one year follow-up had a disease free survival . Among forty patients who completed the two year follow-up , two patients developed local recurrence . CONCLUSIONS Cytoreduction followed by HIPEC improves survival in patients with rectal carcinoma and lymphnode positive and neurovascular involvement Background We evaluate the long-term survival of patients with peritoneal carcinomatosis ( PC ) treated with systemic chemotherapy regimens , and the impact of the of the retrospective peritoneal disease severity score ( PSDSS ) on outcomes . Methods One hundred sixty-seven consecutive patients treated with PC from colorectal cancer between years 1987 - 2006 were identified from a prospect i ve institutional data base . These patients either received no chemotherapy , 5-FU/Leucovorin or Oxaliplatin/Irinotecan-based chemotherapy . Stratification was made according to the retrospective PSDSS that classifies PC patients based on clinical ly relevant factors . Survival analysis was performed using the Kaplan-Meier method and comparison with the log-rank test . Results Median survival was 5 months ( 95 % CI , 3 - 7 months ) for patients who had no chemotherapy , 11 months ( 95 % CI , 6 - 9 months ) for patients treated with 5 FU/LV , and 12 months ( 95 % CI , 4 - 20 months ) for patients treated with Oxaliplatin/Irinotecan-based chemotherapy .  Survival differed between patients treated with chemotherapy compared to those patients who did not receive chemotherapy ( p = 0.026 ) . PSDSS staging was identified as an independent predictor for survival on multivariate analysis [ RR 2.8 ( 95%CI 1.5 - 5.4 ) ; p < 0.001 ] . Conclusion A trend towards improved outcomes is demonstrated from treatment of patients with PC from colorectal cancer using modern systemic chemotherapy . The PSDSS appears to be a useful tool in patient selection and prognostication in PC of colorectal origin Adjuvant chemotherapy with fluorouracil ( FU ) and levamisole or FU/leucovorin ( LV ) has been established as effective adjuvant treatment for patients with stage III colon cancer . Among several other promising treatment strategies in resected colon cancer , intraperitoneal anti-cancer drug administration with its appealing rationale of counteracting microscopic residual disease on peritoneal surfaces and occult metachronous liver metastases by achieving high intraportal drug concentrations has not yet undergone sufficient clinical evaluation . To determine whether a combination of this locoregional therapeutic concept with systemic intravenous administration of FU/LV would yield better results than conventional adjuvant chemoimmunotherapy with FU/levamisole , the present r and omized study was initiated . A total of 241 patients with resected stage III or high-risk stage II ( T4N0M0 ) colon cancer were r and omly assigned to ' st and ard therapy ' with FU and levamisole , given for a duration of 6 months , or to an investigational arm , consisting of LV 200 mg m(-2 ) plus FU 350 mg m(-2 ) , both administered intravenously ( days 1 - 4 ) and intraperitoneally ( days 1 and 3 ) every 4 weeks for a total of six courses . In patients with stage II disease , no significant difference was noted between the two arms after a median follow-up time of 4 years ( range 2.5 - 6 years ) . Among 196 eligible patients with stage III disease , however , a comparative analysis of the two treatment groups suggested both an improvement in disease-free survival ( P = 0.0014 ) and a survival advantage ( P = 0.0005 ) , with an estimated 43 % reduction in mortality rate ( 95 % confidence interval 26 - 70 % ) in favour of the investigational arm . In agreement with its theoretical rationale , combined intraperitoneal and intravenous FU/LV was particularly effective in reducing locoregional tumour recurrences with or without liver or other organ site involvement ( 9 vs 25 patients in the FU/levamisole arm ; P = 0.005 ) . Treatment-associated side-effects were infrequent and generally mild in both arms , although a lower rate of severe ( WHO grade 3 ) adverse reactions was noted in patients receiving locoregional plus intravenous chemotherapy ( 3 % vs 12 % ; P = 0.01 ) . The results of this trial suggest that combined intraperitoneal plus systemic intravenous chemotherapy with FU/LV is a promising adjuvant treatment strategy in patients with surgically resected stage III colon carcinoma Background Early diagnosis and management of peritoneal metastases from colorectal cancer patients are difficult clinical challenges . The aims of this study were to evaluate the clinical significance of  tumor markers and cytology  in peritoneal effusions ( PE ) and peritoneal irrigation fluid ( PI ) and to determine their value as prognostic indicators in this disease . Methods Two hundred thirty-four consecutive patients who underwent abdominal surgery for colorectal cancer from January 2006 to December 2007 were included , and tumor markers and cytology in PE and PI were analyzed prospect ively . Results The incidence of free cancer cells retrieved from peritoneal sample s was 7.9 % . Cytology was positive in 40.0 % by Papanicolaou and Giemsa staining , 73.3 % by hematoxylin and eosin staining of cell blocks , and 66.7 % by carcinoembryonic antigen ( CEA ) and 
    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: Fifty patients were r and omized to receive adjuvant intraperitoneal 5-fluorouracil ( 5-FU , 500 mg/m2/day ) and intravenous leucovorin ( 60 mg/m2/day ) and 51 to receive placebo after curative surgery for colorectal cancer . Treatment started on the day after surgery and continued for 6 days . One case of stomatitis , one of leucopenia and one case of abnormal liver function tests were the only chemotherapy-related toxic effects . From the second day of treatment , pain during intraperitoneal infusions occurred more frequently in the 5-FU group , although statistical significance was only attained on day 2 ( P<0.05 ) . The groups did not differ substantially regarding any other adverse effects , the incidence of surgical complications , second laparotomies , time from surgery to discharge , or premature treatment terminations . The postoperative course after intraperitoneal 5-FU and intravenous leucovorin was thus not more complicated than that in patients treated with placebo . The tolerance was acceptable and chemotherapy-related toxicity was rare . Thus important prerequisites exist for more widespread use of the present regimen in order to evaluate its impact on survival . RésuméCent un patients ont été r and omisés après traitement chirurgical curatif d'un cancer colorectal ; 50 patients ont reçu un traitement adjuvant intrapéritional de 5-FU ( 500 mg/m2/jour ) et intraveineux de Leucovorine ( 60 mg/m2/jour ) et 51 patients ont reçu un  placebo .  Le traitement a été instauré le 1er jour postopératoire et poursuivi durant 6 jours . Les seuls troubles consécutifs à la chimiothérapie observés ont été : 1 cas de stomatite , 1 cas de leucopénie et 1 cas de perturbation des tests hépatiques . A partir du 2ème jour de traitement , des douleurs intraperitionales surviennent plus fréquemment après l'infusion de 5FU bien que la différence ne soit statistiquement significative que pour le 2ème jour ( P<0,05 ) . Les groupes ne différent pas de manière significative quant à d'autres effets secondaires : incidence de complications chirurgicales , taux de relaparotomies , durée des séjours hospitaliers , interruption prématurée du traitement . Les suites postopératoires après injection intrapéritionale de 5FU et intraveineuse de Leucovorine ne sont pas plus compliquées qu'après l'administration d'un placebo . La tolérance est acceptable et la toxicité due à la chimiothérapie est rare . Ainsi , les bases sont établies pour un emploi plus extensif de cette combinaison chimiothérapique dans le but d'établir l'impact sur le taux de survie Background The peritoneum is the second most common site of recurrence in colorectal cancer . Early detection of peritoneal carcinomatosis ( PC ) by imaging is difficult . Patients eventually presenting with clinical ly apparent PC have a poor prognosis . Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited . Only a quarter of patients are eligible for curative treatment , consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy ( CR/HIPEC ) . However , the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate . These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases . Adjuvant hyperthermic intraperitoneal chemotherapy ( HIPEC ) seems to be suitable for this purpose . Without the need for cytoreductive surgery , adjuvant HIPEC can be performed with a low complication rate and short hospital stay . Methods / Design The aim of this study is to determine the effectiveness of  adjuvant HIPEC  in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence . This study will be performed in the nine Dutch HIPEC centres , starting in April 2015 . Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer . After resection of the primary tumour , 176 patients will be r and omized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm , or to systemic chemotherapy only in the control arm . Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection . Oxaliplatin will be used as chemotherapeutic agent , for 30 min at 42 - 43 ° C . Just before HIPEC , 5-fluorouracil and leucovorin will be administered intravenously . Primary endpoint is peritoneal disease-free survival at 18 months . Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA . Discussion Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 % . This reduction is likely to translate into a prolonged overall survival . Trial registration numberNCT02231086 ( Clinical trials.gov Objective : The aim of this prospect i ve study was to analyze the impact of second-look surgery in an attempt to treat peritoneal carcinomatosis ( PC ) at an early stage in a series of patients at high risk of developing PC from colorectal cancer . Background : The prognosis of colorectal PC has recently been improved with hyperthermic intraperitoneal chemotherapy ( HIPEC ) after complete cytoreductive surgery ( CCRS ) , and could be further improved if PC could be treated at an early stage . But , currently , the diagnosis of early PC is not accessible to imaging . Patients and Methods : From 1999 to 2006 , 29 patients without any sign of recurrence on imaging studies underwent second-look surgery 13 months after resection of the primary tumor . Patients were selected according to primary tumor-associated criteria : resected minimal synchronous macroscopic PC ( n = 16 ) , synchronous ovarian metastases ( n = 4 ) , perforated primary tumor ( n = 9 ) . Results : PC was found and treated with CCRS plus HIPEC in 16 of 29 ( 55 % ) cases , corresponding to 10 of 16 patients with initial PC , 3 of 4 patients with synchronous ovarian metastases and 3 of 9 patients with a perforated primary tumor . There was no postoperative mortality , and morbidity ( grade III/IV ) occurred in 14 % of cases . After a median follow-up of 27 months ( range , 6–96 ) , 8 of 16 patients treated with CCRS and HIPEC are free of disease , 4 relapsed in the peritoneum , and 4 developed isolated visceral metastases . Conclusion : Performing second-look surgery at 1 year in selected patients at high risk of developing PC allowed the early detection and treatment of PC in 55 % of cases . Our preliminary results have encouraged us to pursue this strategy and to evaluate it in a prospect i ve multicenter trial BACKGROUND / AIMS The benefits of adjuvant chemotherapy for colorectal cancer has been well accepted over the last decade . Published data so far has been focused in the direction of giving the right chemotherapy dose , schedule , and combinations , in order to increase the efficacy and decrease the toxicity . METHODOLOGY Eighty-seven patients with histological proved stage III rectal carcinoma were subjected to a combined adjuvant modality using laparoscopic heperthermic endoperitoneal chemotherapy ( HIPEC ) and systemic chemotherapy twenty days following the initial surgery . RESULTS Seventy patients who completed a one year follow-up had a disease free survival . Among forty patients who completed the two year follow-up , two patients developed local recurrence . CONCLUSIONS Cytoreduction followed by HIPEC improves survival in patients with rectal carcinoma and lymphnode positive and neurovascular involvement Background We evaluate the long-term survival of patients with peritoneal carcinomatosis ( PC ) treated with systemic chemotherapy regimens , and the impact of the of the retrospective peritoneal disease severity score ( PSDSS ) on outcomes . Methods One hundred sixty-seven consecutive patients treated with PC from colorectal cancer between years 1987 - 2006 were identified from a prospect i ve institutional data base . These patients either received no chemotherapy , 5-FU/Leucovorin or Oxaliplatin/Irinotecan-based chemotherapy . Stratification was made according to the retrospective PSDSS that classifies PC patients based on clinical ly relevant factors . Survival analysis was performed using the Kaplan-Meier method and comparison with the log-rank test . Results Median survival was 5 months ( 95 % CI , 3 - 7 months ) for patients who had no chemotherapy , 11 months ( 95 % CI , 6 - 9 months ) for patients treated with 5 FU/LV , and 12 months ( 95 % CI , 4 - 20 months ) for patients treated with Oxaliplatin/Irinotecan-based chemotherapy .  Survival differed between patients treated with chemotherapy compared to those patients who did not receive chemotherapy ( p = 0.026 ) . PSDSS staging was identified as an independent predictor for survival on multivariate analysis [ RR 2.8 ( 95%CI 1.5 - 5.4 ) ; p < 0.001 ] . Conclusion A trend towards improved outcomes is demonstrated from treatment of patients with PC from colorectal cancer using modern systemic chemotherapy . The PSDSS appears to be a useful tool in patient selection and prognostication in PC of colorectal origin Adjuvant chemotherapy with fluorouracil ( FU ) and levamisole or FU/leucovorin ( LV ) has been established as effective adjuvant treatment for patients with stage III colon cancer . Among several other promising treatment strategies in resected colon cancer , intraperitoneal anti-cancer drug administration with its appealing rationale of counteracting microscopic residual disease on peritoneal surfaces and occult metachronous liver metastases by achieving high intraportal drug concentrations has not yet undergone sufficient clinical evaluation . To determine whether a combination of this locoregional therapeutic concept with systemic intravenous administration of FU/LV would yield better results than conventional adjuvant chemoimmunotherapy with FU/levamisole , the present r and omized study was initiated . A total of 241 patients with resected stage III or high-risk stage II ( T4N0M0 ) colon cancer were r and omly assigned to ' st and ard therapy ' with FU and levamisole , given for a duration of 6 months , or to an investigational arm , consisting of LV 200 mg m(-2 ) plus FU 350 mg m(-2 ) , both administered intravenously ( days 1 - 4 ) and intraperitoneally ( days 1 and 3 ) every 4 weeks for a total of six courses . In patients with stage II disease , no significant difference was noted between the two arms after a median follow-up time of 4 years ( range 2.5 - 6 years ) . Among 196 eligible patients with stage III disease , however , a comparative analysis of the two treatment groups suggested both an improvement in disease-free survival ( P = 0.0014 ) and a survival advantage ( P = 0.0005 ) , with an estimated 43 % reduction in mortality rate ( 95 % confidence interval 26 - 70 % ) in favour of the investigational arm . In agreement with its theoretical rationale , combined intraperitoneal and intravenous FU/LV was particularly effective in reducing locoregional tumour recurrences with or without liver or other organ site involvement ( 9 vs 25 patients in the FU/levamisole arm ; P = 0.005 ) . Treatment-associated side-effects were infrequent and generally mild in both arms , although a lower rate of severe ( WHO grade 3 ) adverse reactions was noted in patients receiving locoregional plus intravenous chemotherapy ( 3 % vs 12 % ; P = 0.01 ) . The results of this trial suggest that combined intraperitoneal plus systemic intravenous chemotherapy with FU/LV is a promising adjuvant treatment strategy in patients with surgically resected stage III colon carcinoma Background Early diagnosis and management of peritoneal metastases from colorectal cancer patients are difficult clinical challenges . The aims of this study were to evaluate the clinical significance of  tumor markers and cytology  in peritoneal effusions ( PE ) and peritoneal irrigation fluid ( PI ) and to determine their value as prognostic indicators in this disease . Methods Two hundred thirty-four consecutive patients who underwent abdominal surgery for colorectal cancer from January 2006 to December 2007 were included , and tumor markers and cytology in PE and PI were analyzed prospect ively . Results The incidence of free cancer cells retrieved from peritoneal sample s was 7.9 % . Cytology was positive in 40.0 % by Papanicolaou and Giemsa staining , 73.3 % by hematoxylin and eosin staining of cell blocks , and 66.7 % by carcinoembryonic antigen ( CEA ) and 
    Output:
    