Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial Results of Systematic Second-look Surgery Plus HIPEC in Asymptomatic Patients Presenting a High Risk of Developing Colorectal Peritoneal Carcinomatosis Outcomes of colorectal cancer patients with peritoneal carcinomatosis treated with chemotherapy with and without targeted therapy. Results of Systematic Second-Look Surgery in Patients at High Risk of Developing Colorectal Peritoneal Carcinomatosis Second-look surgery plus HIPEC for patients with colorectal cancer at high risk of peritoneal carcinomatosis: Should we resect the initial anastomosis? An observational study. Laparoscopic hyperthermic intraperitoneal chemotherapy as adjuvant modality following radical surgery for advanced rectal cancer a new look to an old problem. Prospective, randomized trial of intravenous versus intraperitoneal 5-fluorouracil in patients with advanced primary colon or rectal cancer. Effects of Intraperitoneal Chemotherapy with Mitomycin C on the Prevention of Peritoneal Recurrence in Colorectal Cancer Patients with Positive Peritoneal Lavage Cytology Findings Impact of peritoneal carcinomatosis in the disease history of colorectal cancer management: a longitudinal experience of 2406 patients over two decades Perioperative systemic chemotherapy in peritoneal carcinomatosis of lymph node positive colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Free Colorectal Cancer Cells on the Peritoneal Surface: Correlation With Pathologic Variables and Survival Hyperthermic intraperitoneal chemotherapy during primary tumour resection limits extent of bowel resection compared to two-stage treatment. HIPEC in T4a colon cancer: a defendable treatment to improve oncologic outcome? Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. Disseminated Single Tumor Cells as Detected by Real-Time Quantitative Polymerase Chain Reaction Represent a Prognostic Factor in Patients Undergoing Surgery for Colorectal Cancer Feasibility of adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy in a short stay setting in patients with colorectal cancer at high risk of peritoneal carcinomatosis. The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin.
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 h later . Results The mean follow-up period was 83.1 months . According to univariate analyses of all 52 patients and the subgroup of 36 patients with stage II or III tumors , patients with IPC  had a significantly better peritoneal recurrence-free survival and cancer-specific survival than patients who did not receive IPC  ( P < 0.005 ) . In multivariate analysis , IPC remained an independent prognostic factor for peritoneal recurrence-free survival in all patients . Conclusions It appears that IPC with MMC is an effective treatment to prevent peritoneal recurrence and prolong the cancer-specific survival in CRC patients without peritoneal dissemination , but who have positive peritoneal lavage cytology . It is necessary to verify the effectiveness of IPC with MMC in a prospect i ve trial 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 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 BACKGROUND Clinicopathologic staging of colorectal cancer remains the best predictor of survival . Prognostication for an individual with colorectal cancer remains elusive . This study was design ed to investigate the incidence of free surface colorectal cancer cells detected by cytology during elective open curative resection  , to correlate their presence with particular clinicopathologic variables and determine whether their presence was predictive of cancer-specific survival . METHODS Over a six-year period in one institution , all elective colon and intraperitoneal rectal cancer specimens were assessed during primary resection  for the presence of free colorectal cancer cells by means of a simple and tested specimen imprint cytology methodology . Clinicopathologic variables were assessed prospect ively and blinded to cytology results . All patients were followed up routinely until death and if the patient was not seen within the last six months , information was obtained from the New South Wales Registry of Births , Deaths and Marriages in Australia . RESULTS Overall , 26 of 281 ( 9.25 percent ) colorectal cancers had positive cytology for cancer cells on the peritoneal surface of the bowel . Poorly differentiated tumors were significantly associated with positive cytology . Tumor penetration , presence of vascular or neural invasion , mucinous characteristics , lymph node status , and operative procedure performed were not statistically significant predictors of positive cytology . Overall , 43 of the 281 patients ( 15.3 percent ) died during the mean follow-up period of 49.2 months from cancer-related deaths . Of these patients , 8 had positive cytology and 35 had negative cytology results . Cancer-specific survival assessed with the log-rank test was significantly associated with positive cytology in univariate ( P = 0.008 ) and multivariate analysis ( P < 0.001 ) . CONCLUSION In this study , the presence of free surface colorectal cancer cells has been shown to be predictive of survival and is independent of direct peritoneal invasion and lymph node status . Thus , further assessment of this simple prognostic variable is warranted and selection of patients with positive cytology for possible adjuvant therapies may be beneficial AIM To compare the clinical outcome of a one-stage , primary tumour resection and hyperthermic intraperitoneal chemotherapy ( HIPEC ) procedure , versus a two-stage procedure of tumour resection and secondary HIPEC in colorectal cancer ( CRC ) patients with synchronous peritoneal carcinomatosis . METHODS A prospect i ve data base of all patients treated with HIPEC in the St. Antonius Hospital in the Netherl and s between 2005 and 2012 was analysed . RESULTS A total of 72 patients with synchronous peritoneal carcinomatosis ( PC ) from CRC were included . In 20 patients ( 27.8 % ) the primary tumour was resected simultaneously with HIPEC ( early referral ) . In the other 52 patients ( 72.2 % ) the primary tumour was resected prior to the HIPEC procedure ( late referral ) . During CRS + HIPEC following late referral , 22 ( 59.5 % ) of the 37 anastomoses of the earlier operation were resected , revealing malignancy in 12 ( 54.5 % ) on histopathological examination . In twenty ( 27.8 % ) patients a permanent colostomy was constructed after HIPEC . Ten of these patients had complete bowel continuity after earlier primary resection . The relaparotomy rate was higher in patients after a resection of a previous anastomosis ( 36.4 % ) compared to 12 % in the rest of the patients ( P = 0.02 ) . CONCLUSIONS Resection of the primary tumour simultaneously with HIPEC in patients with synchronous PC from CRC may prevent extended bowel resections and permanent colostomy . Our data support early referral of patients with PC from colorectal cancer BACKGROUND Adequate estimation of the potential benefits of ' adjuvant ' hyperthermia and intraperitoneal chemotherapy ( HIPEC ) in T4 patients through assessment of the burden of peritoneal carcinomatosis ( PC ) in T4 tumors and the risk of PC as the only metastatic site . PATIENTS AND METHODS Analysis of prospect ively collected data on patients who underwent surgery for colon cancer ( Jan 2004-Jan 2007 ) . RESULTS About 379 patients ( M/F = 204/175 ) were included , with a median age of 71.8 years ( range 35.4 - 95.0 ) : 39 stage I , 126 stage II , 89 stage III , 116 stage IV disease ( + 9 with unknown stage ) . The median follow-up was 34.8months [ range 0.0 - 79.4 ] . The 3- and 5-year overall survival rates ( OS ) were 68.4 % ( 95 % confidence interval ( CI ) 63.9%-72.4 % ) and 60.3 % ( 95%CI 55.6%-64.7 % ) . Relapse analysis was restricted to stages II-III T3 ( N = 154 ) and T4 tumors ( N = 19 ) with complete relapse data , of which 13.2 % developed PC . PC has a detrimental effect on OS [ HR 6.3 ( 95%CI : 3.1 - 13.0 , P < 0.0001 ) ] . 50 % of T4a and 20 % of T4b developed PC . The 1- and 3-year PC percentage was significantly lower for T3 ( 4.5 % and 9.3 % ) than T4 tumors ( 15.6 % and 36.7 % ) ( P = 0.008 ) . PC was the only metastatic site in 3/15 T3 [ proportion 0.20 , 95%CI ( 0.043 - 0.481 ) ] and 5/8 T4 tumors with PC [ proportion 0.625 , 95%CI ( 0.245 - 0.915 ) ] ( P = 0.071 ) . CONCLUSIONS T4a colon tumors have a significantly higher risk of developing PC . Twenty-five percent ( 5/19 ) of stages II-III T4 tumors develop PC as the only metastatic site . This could define the possible window of opportunity for adjuvant HIPEC to prevent PC 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 Objective To evaluate the clinical relevance of real-time quantitative polymerase chain reaction ( qPCR ) detection of CEA and CK20 transcripts , as potentially related to tumor cell dissemination , in blood and peritoneal lavage from patients undergoing surgery for colorectal cancer . Summary Background Data Dissemination of single colorectal cancer cells in the peritoneal cavity , as well as in tumor drainage and peripheral blood vessels , might play a role in the metastasis process , thus affecting the clinical course . However , this phenomenon needs further elucidation . Methods In a prospect i ve study the authors evaluated the potential of qPCR in the detection of CEA and /or CK20 transcripts in the peritoneal lavage fluid and in the peripheral and mesenteric venous blood of 39 patients undergoing curative resection for colorectal cancer .  Peritoneal lavage and peripheral blood was sample d before and after tumor resection ; mesenteric venous blood was sample d from the major tumor-draining vein immediately before clamping . After RNA extraction and reverse transcription , qPCR was performed using specific cDNA primers and probes for CEA and CK20 . The dichotomous results from the qPCR were used as a predictor along with other covariates in Cox proportional hazard regression models of long-term outcome ( disease-free survival and overall survival ) . Results Of 39 patients , 11 were positive . The median follow-up at analysis was 31 months for all patients . The dichotomous qPCR covariate was significant , with P = .001 and .0035 for disease-free survival and overall survival , respectively , in the proportional hazard regression models with only qPCR . In seven patients , disseminated colorectal cancer cells were found in the peritoneal lavage fluid but not in blood specimens ; five of these patients ( 71 % ) had recurrence . Conclusions These data suggest that detection of mRNA coding for CEA and /or CK20 using qPCR has potential clinical utility as a prognostic marker and should be evaluated in larger clinical studies . Identification of patients at high risk for metastatic disease after curative resection of colorectal cancer might be improved by analyzing peritoneal lavage specimens in addition to blood sample s. This is based on the observation that in more than half of qPCR-positive patients , disseminated colorectal cancer cells were detected in peritoneal lavage specimens but not in blood sample s , and that 71 % of them had recurrence INTRODUCTION Treatment of peritoneal carcinomatosis ( PC ) of colorectal cancer ( CRC ) origin is relatively ineffective and associated with morbidity . This raises the question whether we should focus on prevention of the development of PC . We determined the feasibility of adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy ( HIPEC ) in a short stay setting . METHODS A prospect i ve single centre pilot study was conducted between January 2011 and July 2012 . Ten patients at risk of developing PC of CRC origin were included .  Laparoscopic HIPEC using Mitomycin-C ( 90 min ; inflow temperature 42 - 43 ° C ) was performed within several weeks after primary resection of CRC and was considered feasible when postoperative hospital stay was three days or shorter in at least six patients , and if a maximum of one conversion and one re-admission within 30 days occurred . RESULTS HIPEC was performed after a median of 6 weeks ( range 3 - 9 weeks ) . Postoperatively , five patients were discharged at day one , four patients at day two and one patient at day three . Laparoscopic adhesiolysis result ed in small bowel injury in one patient , but no conversion to open surgery and no postoperative complications were observed . One patient was readmitted within 30 days due to a clostridium infection . The postoperative course was uneventful for the remaining patients . CONCLUSION Adjuvant laparoscopic HIPEC appeared to be feasible in a short stay setting based on this small pilot study . The necessity of adhesiolysis determines the complexity of the procedure and requires an operating team with experience in minimally invasive abdominal surgery BACKGROUND Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy ( HIPEC ) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis ( CRCPC ) . Tremendous variations exist in the HIPEC delivery . METHODS The American Society of Peritoneal Surface Malignancies ( ASPSM ) examined the overall survival in patients with CRCPC who underwent a complete cytoreduction and HIPEC with Oxaliplatin vs. Mitomycin C ( MMC )  , stratifying them by the Peritoneal Surface Disease Severity Score ( PSDSS ) . RESULTS Median overall survival ( OS ) of 539 patients with complete cytoreduction was 32.6 months , 32.7 months for the MMC group and 31.4 months for the Oxaliplatin group ( P = 0.925 ) . However , when stratified by PSDSS , median OS rates in PSDSS I/II patients were 54.3 months in those receiving MMC vs. 28.2 months in those receiving oxaliplatin ( P = 0.012 ) , whereas in PSDSS III/IV patients , median OS rates were 19.4 months in those receiving MMC vs. 30.4 months in those receiving Oxaliplatin ( P = 0.427 ) . CONCLUSION These data suggest that MMC might be a better agent for HIPEC delivery than Oxaliplatin in patients with CRCPC , favorable histologies and low burden of disease ( PSDSS I/II ) undergoing complete cytoreduction . Prospect i ve studies are warranted , which stratify patients by their PSDSS and r and omize them to HIPEC with MMC vs. Oxaliplatin Survival benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion was demonstrated by a prospect i ve r and omized trial for colorectal peritoneal carcinomatosis . Because of a recent substantial improvement in chemotherapy , the authors analyzed treatment options of colorectal carcinomatosis in the current era 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 %
PURPOSE Τo evaluate all available data on the effect of preemptive intervention in patients who have curative surgery for colorectal cancer ( CRC ) and are at high risk to develop peritoneal carcinomatosis ( PC ) .