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 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 Purpose : To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy ( HIPEC ) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis ( PC ) . Patients and Methods : From 1999 to 2009 , 41 patients without any sign of recurrence on imaging studies underwent second-look surgery  aim ed at treating limited PC earlier and more easily . They were selected based on 3 primary tumor-associated criteria : resected minimal synchronous macroscopic PC ( n = 25 ) , synchronous ovarian metastases ( n = 8) , and perforation ( n = 8) . Results : PC was found and treated with complete surgery plus HIPEC in 23 of the 41 ( 56 % ) patients . The other patients underwent complete abdominal exploration plus systematic HIPEC . Median follow-up was 30 ( 9–109 ) months . One patient died postoperatively at day 69 . Grade 3 - 4 morbidity was low ( 9.7 % ) . The 5-year overall survival rate was 90 % and the 5-year disease-free survival rate was 44 % . Peritoneal recurrences occurred in 7 patients ( 17 % ) , 6 of whom had macroscopic PC discovered during the second-look ( 26 % ) , and one patient had no macroscopic PC ( 6 % ) . In the univariate analysis , the presence of PC at second-look surgery was a significant risk factor for recurrence ( P = 0.006 ) . Conclusion : Selection criteria for high-risk patients appear to be accurate . In these patients , the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage , yielding promising results . This study has allowed us to design a multicentric r and omized trial ( comparing the second-look + HIPEC approach versus st and ard follow-up alone ) , which is beginning BACKGROUND Although systemic therapies have shown to result in survival benefit in patients with metastatic colorectal cancer ( mCRC ) , outcomes in patients with peritoneal carcinomatosis ( PC ) are poor . No data are available on outcomes of current chemotherapy schedules plus targeted agents in mCRC patients with PC . METHODS Previously untreated mCRC patients treated with chemotherapy in the CAIRO study and with chemotherapy and targeted therapy in the CAIRO2 study were included and retrospectively analysed according to presence or absence of PC at r and omisation . Patient demographics , primary tumour characteristics , progression-free survival ( PFS ) , overall survival ( OS ) , and occurrence of toxicity were evaluated . RESULTS Thirty-four patients with PC were identified in the CAIRO study and 47 patients in the CAIRO2 study .  Median OS was decreased for patients with PC compared with patients without PC ( CAIRO : 10.4 versus 17.3 months , respectively ( p ≤ 0.001 ) ; CAIRO2 : 15.2 versus 20.7 months , respectively ( p < 0.001 ) ) . Median number of treatment cycles did not differ between patients with or without PC in both studies . Occurrence of major toxicity was more frequent in patients with PC treated with sequential chemotherapy in the CAIRO study as compared to patients without PC . This was not reflected in reasons to discontinue treatment . In the CAIRO2 study , no differences in major toxicity were observed . CONCLUSION Our data demonstrate decreased efficacy of current st and ard chemotherapy with and without targeted agents in mCRC patients with PC . This suggests that the poor outcome can not be explained by undertreatment or increased susceptibility to toxicity , but rather by relative resistance to treatment 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 Cytoreductive surgery ( CCRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) improves the overall survival in selected cases of peritoneal carcinomatosis ( PC ) of colorectal origin . Second-look surgery in asymptomatic patients at high risk of developing PC has shown encouraging results . This study aims at identifying cases in which initial anastomosis should be resected . METHODS Patients treated by second-look surgery and HIPEC were identified from a prospect i ve data base . High-risk was defined as synchronous resected and minimal PC , ovarian metastasis or perforated primary tumor . Patients were divided in two groups based on intra-operative evaluation of the anastomosis : possibly-invaded ( PI ) and unlikely-invaded ( UI ) . PI was defined as 1 ) PC away from the anastomosis , 2 ) nodules resting on the anastomosis 3 ) anastomotic stenosis or anastomotic thickening . Anastomosis in the PI group were resected . RESULTS Forty patients were included : 12 in the PI group and 28 in the UI group .  Incidence of pathological anastomotic invasion was 42 % ( 5 on 12 patients ) in the PI group . In the UI group , 2 patients had anastomotic recurrence , both associated with peritoneal recurrence . Morbidity and mortality was not influenced by anastomosis resection . The presence of suspicious nodules on the anastomosis had a sensitivity of 100 % and a specificity of 89 % in predicting anastomotic invasion . CONCLUSION In second-look surgery and HIPEC for colorectal cancer at high-risk of PC , anastomosis should be resected when overlying PC nodules are found . This attitude is supported by high sensitivity of this finding for anastomotic invasion and low morbidity related to anastomotic resection 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 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 The detection of intraperitoneal free cancer cells in colorectal cancer ( CRC ) patients is associated with a poorer prognosis . The aim of this study was to investigate the effects of intraperitoneal chemotherapy ( IPC ) with mitomycin C ( MMC ) on preventing peritoneal recurrence in CRC patients with positive peritoneal lavage cytology findings . Methods A total of 52 CRC patients who had no clinical ly confirmed peritoneal dissemination and whose status of peritoneal lavage cytology was positive were investigated . Conventional peritoneal lavage cytology was performed . Overall , 31 of the 52 patients ( 59.6 % ) were administered IPC with MMC . Before closure of the abdomen , 4 silicon catheters were inserted into peritoneal cavity . After closure , the perfusate ( diluting 20 mg MMC with 500 ml saline ) was instilled from the catheter , and all catheters were clumped . All catheters were opened 1 
    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 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 Purpose : To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy ( HIPEC ) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis ( PC ) . Patients and Methods : From 1999 to 2009 , 41 patients without any sign of recurrence on imaging studies underwent second-look surgery  aim ed at treating limited PC earlier and more easily . They were selected based on 3 primary tumor-associated criteria : resected minimal synchronous macroscopic PC ( n = 25 ) , synchronous ovarian metastases ( n = 8) , and perforation ( n = 8) . Results : PC was found and treated with complete surgery plus HIPEC in 23 of the 41 ( 56 % ) patients . The other patients underwent complete abdominal exploration plus systematic HIPEC . Median follow-up was 30 ( 9–109 ) months . One patient died postoperatively at day 69 . Grade 3 - 4 morbidity was low ( 9.7 % ) . The 5-year overall survival rate was 90 % and the 5-year disease-free survival rate was 44 % . Peritoneal recurrences occurred in 7 patients ( 17 % ) , 6 of whom had macroscopic PC discovered during the second-look ( 26 % ) , and one patient had no macroscopic PC ( 6 % ) . In the univariate analysis , the presence of PC at second-look surgery was a significant risk factor for recurrence ( P = 0.006 ) . Conclusion : Selection criteria for high-risk patients appear to be accurate . In these patients , the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage , yielding promising results . This study has allowed us to design a multicentric r and omized trial ( comparing the second-look + HIPEC approach versus st and ard follow-up alone ) , which is beginning BACKGROUND Although systemic therapies have shown to result in survival benefit in patients with metastatic colorectal cancer ( mCRC ) , outcomes in patients with peritoneal carcinomatosis ( PC ) are poor . No data are available on outcomes of current chemotherapy schedules plus targeted agents in mCRC patients with PC . METHODS Previously untreated mCRC patients treated with chemotherapy in the CAIRO study and with chemotherapy and targeted therapy in the CAIRO2 study were included and retrospectively analysed according to presence or absence of PC at r and omisation . Patient demographics , primary tumour characteristics , progression-free survival ( PFS ) , overall survival ( OS ) , and occurrence of toxicity were evaluated . RESULTS Thirty-four patients with PC were identified in the CAIRO study and 47 patients in the CAIRO2 study .  Median OS was decreased for patients with PC compared with patients without PC ( CAIRO : 10.4 versus 17.3 months , respectively ( p ≤ 0.001 ) ; CAIRO2 : 15.2 versus 20.7 months , respectively ( p < 0.001 ) ) . Median number of treatment cycles did not differ between patients with or without PC in both studies . Occurrence of major toxicity was more frequent in patients with PC treated with sequential chemotherapy in the CAIRO study as compared to patients without PC . This was not reflected in reasons to discontinue treatment . In the CAIRO2 study , no differences in major toxicity were observed . CONCLUSION Our data demonstrate decreased efficacy of current st and ard chemotherapy with and without targeted agents in mCRC patients with PC . This suggests that the poor outcome can not be explained by undertreatment or increased susceptibility to toxicity , but rather by relative resistance to treatment 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 Cytoreductive surgery ( CCRS ) and hyperthermic intraperitoneal chemotherapy ( HIPEC ) improves the overall survival in selected cases of peritoneal carcinomatosis ( PC ) of colorectal origin . Second-look surgery in asymptomatic patients at high risk of developing PC has shown encouraging results . This study aims at identifying cases in which initial anastomosis should be resected . METHODS Patients treated by second-look surgery and HIPEC were identified from a prospect i ve data base . High-risk was defined as synchronous resected and minimal PC , ovarian metastasis or perforated primary tumor . Patients were divided in two groups based on intra-operative evaluation of the anastomosis : possibly-invaded ( PI ) and unlikely-invaded ( UI ) . PI was defined as 1 ) PC away from the anastomosis , 2 ) nodules resting on the anastomosis 3 ) anastomotic stenosis or anastomotic thickening . Anastomosis in the PI group were resected . RESULTS Forty patients were included : 12 in the PI group and 28 in the UI group .  Incidence of pathological anastomotic invasion was 42 % ( 5 on 12 patients ) in the PI group . In the UI group , 2 patients had anastomotic recurrence , both associated with peritoneal recurrence . Morbidity and mortality was not influenced by anastomosis resection . The presence of suspicious nodules on the anastomosis had a sensitivity of 100 % and a specificity of 89 % in predicting anastomotic invasion . CONCLUSION In second-look surgery and HIPEC for colorectal cancer at high-risk of PC , anastomosis should be resected when overlying PC nodules are found . This attitude is supported by high sensitivity of this finding for anastomotic invasion and low morbidity related to anastomotic resection 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 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 The detection of intraperitoneal free cancer cells in colorectal cancer ( CRC ) patients is associated with a poorer prognosis . The aim of this study was to investigate the effects of intraperitoneal chemotherapy ( IPC ) with mitomycin C ( MMC ) on preventing peritoneal recurrence in CRC patients with positive peritoneal lavage cytology findings . Methods A total of 52 CRC patients who had no clinical ly confirmed peritoneal dissemination and whose status of peritoneal lavage cytology was positive were investigated . Conventional peritoneal lavage cytology was performed . Overall , 31 of the 52 patients ( 59.6 % ) were administered IPC with MMC . Before closure of the abdomen , 4 silicon catheters were inserted into peritoneal cavity . After closure , the perfusate ( diluting 20 mg MMC with 500 ml saline ) was instilled from the catheter , and all catheters were clumped . All catheters were opened 1 
    Output:
    