Immunocytochemically detected free peritoneal tumour cells (FPTC) are a strong prognostic factor in gastric carcinoma Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patients Prospective randomized trial of early postoperative intraperitoneal chemotherapy as an adjuvant to resectable gastric cancer. Positive Peritoneal Cytology in Patients with Gastric Cancer: Natural History and Outcome of 291 Patients The Value of Peritoneal Cytology as a Preoperative Predictor in Patients With Gastric Carcinoma Undergoing a Curative Resection Does the intraoperative peritoneal lavage cytology add prognostic information in patients with potentially curative gastric resection? Is Borrmann type IV gastric carcinoma a surgical disease? An old problem revisited with reference to the result of peritoneal washing cytology. Phase II Clinical Trial of Postoperative S-1 Monotherapy for Gastric Cancer Patients with Free Intraperitoneal Cancer Cells Detected by Real-Time RT-PCR Prognostic value of positive cytology findings from abdominal washings in patients with gastric cancer Extensive Intraoperative Peritoneal Lavage as a Standard Prophylactic Strategy for Peritoneal Recurrence in Patients with Gastric Carcinoma A phase II study of radical surgery followed by postoperative chemotherapy with S-1 for gastric carcinoma with free cancer cells in the peritoneal cavity (CCOG0301 study). Peritoneal washing cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection.
Summary We prospect ively investigated the prognostic significance of free peritoneal tumour cells ( FPTC ) in a series of 118 patients with completely resected gastric carcinoma .  Immunocytochemistry with the monoclonal antibody Ber-Ep4 was performed on cytospins from intraoperative peritoneal lavage specimens . Twenty-three patients ( 20 % ) had FPTC  which was significantly correlated with pT and pN categories , stage , tumour size , lymphatic invasion , Laurèn and WHO classifications and perigastric adipose tissue metastases . The median survival time for all FPTC positive compared with negative patients was significantly shorter ( 11 compared with > 72 months ) , with estimated 5-year survival rates of 8 % vs. 60 % . None of the patients with FPTC had an early gastric cancer . In advanced tumour subgroups without and with serosal invasion ( n = 59 and 35 ) , there were 19 % and 34 % with FPTC .  Multivariate survival analysis showed nodal status , FPTC , mesenteric lymphangiosis , and lymph node metastasis to the compartment III to be independent prognostic factors with relative risks of 6.6 , 4.5 , 2.9 and 2.2 respectively . Recurrent disease occurred in 91 % of FPTC-positive and in 38 % of FPTC-negative patients . FPTC had a positive predictive value of 91 % and a specificity of 97 % for tumour recurrence .  FPTC is a strong negative , independent prognostic indicator for survival in gastric carcinoma Prediction of peritoneal relapse is extremely important for gastric cancer patients after curative surgery . The present study prospect ively vali date s the prognostic ability of quantifying carcinoembryonic antigen ( CEA ) mRNA in peritoneal washes by real-time reverse transcriptase – polymerase chain reaction . Based on a retrospective study of 197 curatively resected gastric cancer patients ( training set ) , we determined a cutoff value of CEA mRNA using receiver-operating characteristic curve . We used this cutoff value to vali date the risk of peritoneal recurrence in a new cohort of 86 gastric cancer patients ( validation set ) between July 2000 and December 2002 in a prospect i ve study . During the median 30 months of postoperative surveillance , 20 of the 86 patients died , and 13 of the 20 developed peritoneal metastases . Peritoneal recurrence-free survival as well as overall survival was significantly worse in patients with positive CEA mRNA ( P<0.0001 ) . Multivariate analysis with the Cox proportional hazards model showed that positive CEA mRNA was a significant independent risk factor with both survival ( P=0.0130 ) and peritoneal recurrence-free survival ( P=0.0006 ) as end points . These results indicate that quantitation of CEA mRNA in peritoneal washes is a reliable prognostic indicator of peritoneal recurrence in the clinical setting OBJECTIVE Surgeons have postulated on numerous occasions that cancer resection may participate in the dissemination of a malignancy . This r and omized trial sought to determine whether a large volume of chemotherapy solution used perioperatively to flood the peritoneal cavity could eliminate microscopic residual disease and thereby improve survival of patients with gastric cancer . SUMMARY BACKGROUND DATA Surgical treatment failures in patients with gastric cancer are confined to the abdomen in most patients . Resection site and peritoneal surface spread , along with liver metastases , are the most common areas of recurrence . Survival and quality of life of patients with gastric cancer would be improved if disease progression at these anatomic sites was reduced . METHODS In a prospect i ve r and omized trial of 248 patients , intraperitoneal mitomycin C on day 1 and intraperitoneal 5-fluorouracil on days 2 through 5 were administered after gastric cancer resection .  Patients who were thought to have stage II or stage III disease were r and omized after resection to surgery alone versus surgery plus early postoperative intraperitoneal chemotherapy . After final pathologic examinations , there were 39 patients with stage I , 50 with stage II 95 with stage III , and 64 with resected stage IV cancer . RESULTS The 5-year survival of the surgery-only group was 29.3 % , and the surgery-plus-intraperitoneal chemotherapy group was 38.7 % ( p = 0.219 ) . In a subset analysis , the patients with stage I , stage II , and stage IV disease showed no statistically significant difference in survival . The 5-year survival rate of patients with stage III disease who underwent surgery only was 18.4 % versus a survival rate of 49.1 % for patients who underwent surgery plus intraperitoneal chemotherapy ( p = 0.011 ) . CONCLUSIONS In a subset analysis , patients with stage III gastric cancer have shown a statistically significant improvement in survival when treated with perioperative intraperitoneal chemotherapy . Further studies in patients with gastric cancer with surgically directed chemotherapy are suggested Background .Positive peritoneal cytology is a predictor of poor survival in patients with gastric cancer . Our aim is to more clearly define the natural history of this cohort . Methods . Review of a prospect ively maintained gastric cancer data base of patients who had diagnostic laparoscopy with peritoneal washings .  Clinicopathologic and treatmentrelated variables were obtained . Univariate and multivariate analyses were performed for factors associated with disease-specific survival ( DSS ) . Results .From January 1993 to April 2009 , a total of 1241 patients with gastric cancer underwent laparoscopy with peritoneal washings ; 291 ( 23 % ) had positive cytology . There were 198 patients ( 68 % ) who had visible metastases discovered at laparoscopy ( M1 ) , and 93 patients ( 32 % ) were without gross evidence of advanced disease ( M1 Cyt+ ) . The median DSS for the entire cohort was 1 year ; for M1 , DSS was 0.8 years , and for M1 Cyt+ , DSS was 1.3 years . At baseline , independent predictors of worse DSS were poor performance status , M1 disease , and diffuse tumors . Among the subset of patients with M1 Cyt + disease , performance status was the strongest independent predictor of DSS . A total of 48 of the 291 Cyt + patients had repeat staging laparoscopy after chemotherapy . Compared with patients who had persistently positive cytology ( n = 21 ) , those who converted to negative cytology ( n = 27 ) had a significant improvement in DSS ( 2.5 years vs. 1.4 years , P = 0.0003 ) . Conclusions . Patients with positive cytology as the only evidence of advanced disease exhibit a poor outcome ; however , clearing of Cyt + disease by chemotherapy is associated with a statistically significant improvement in DSS . The role for gastrectomy in patients with positive peritoneal cytology remains uncertain Background Although positive peritoneal cytology is associated with poor prognosis , it has not been found to be independently predictive of outcome when evaluated in context of post-resection pathologic T and N stage . This study was undertaken to evaluate the predictive value of positive cytology in context of other prognostic factors available prior to surgery in patients undergoing R0 resection for gastric cancer , to assess its role in selecting patients for appropriate treatment prior to surgical resection . Methods Clinical variables for all patients undergoing R0 resection for gastric adenocarcinoma at Memorial Sloan-Kettering Cancer Center from 1993–2002 were review ed from a prospect i ve data base . Patients underwent preoperative assessment of T and N stage with CT scan , laparoscopy , and endoscopic and /or laparoscopic ultrasound . Peritoneal cytology was obtained in all patients . Results Patients with gastric cancer ( n = 371 ) underwent R0 resection and staging laparoscopy with peritoneal washings ; 24 patients ( 6.5 % ) had positive peritoneal cytology . Positive cytology was associated with advanced T stage ( P = 0.02 ) but not with nodal positivity ( P = 0.11 ) . Median survival of patients with positive cytology was 14.8 months vs. 98.5 months for patients with negative cytology ( P < 0.001 ) . Multivariate analysis identified preoperative T stage , preoperative N stage , site , and cytology as significant predictors of outcome . Positive cytology was the preoperative factor most predictive of death from gastric cancer ( RR 2.7 , P < 0.001 ) . Conclusions Positive cytology is information potentially available preoperatively that identifies a patient population at very high risk for early recurrence and death after curative resection of gastric cancer Peritoneal recurrence is the foremost pattern of failure after potentially curative resection for gastric cancer . Our aim was to evaluate the prognostic value of intraperitoneal free cancer cells ( IFCCs ) in peritoneal lavage of patients who underwent potentially curative resection for gastric carcinoma . Two hundred twenty patients with gastric cancer stage I , II , or III were prospect ively evaluated with peritoneal lavage and cytologic examination . Aspirated fluid from the abdominal cavity was centrifuged and subjected to Papanicolaou staining .  The mean age was 60.9 years ( range , 21–89 years ) , and 63.6 % were men . IFCCs were detected in 6.8 % of the patients ; suspicious in 2.7 % , and negative in 84.5 % . No judgment could be given in 5.9 % of the cases . Invasion of the gastric serosa ( pT3 ) was observed in all positive cytology patients . Patients with IFCCs had a mean survival time of 10.5 months , while those with negative IFCC had a mean survival time of 61 months ( P = 0.00001 ) . There was no correlation between the presence of IFCCs and tumor size , histology , pN , or tumor site . Our conclusions are that ( 1 ) positive cytology indicates a poor prognosis in patients who underwent potentially curative gastric resection  and ( 2 ) peritoneal lavage cytology improves staging in assessing these patients and may alter their therapeutic approach BACKGROUND AND OBJECTIVES Borrmann type IV gastric carcinoma ( B-4 ) remains a disease with poor prognosis despite an aggressive surgical approach . Cytology examination of the peritoneal washes is an established prognostic factor for gastric carcinoma in general , and may be useful for identifying adequate treatment strategy for B-4 . METHODS Pathologic data from 70 patients with B-4 who underwent laparotomy and peritoneal washing cytology during the recent 6 years were retrieved from a prospect i ve computer data base and review ed . Prognostic significance of the cytology examination along with other known clinicopathologic variables was evaluated by univariate and multivariate analyses . RESULTS Long-term survivors were observed only among the patients who were treated with curative R0 resection . Prognosis of the patients with positive cytology and no other residual disease ( R1 ) was extremely poor and was equivalent to that of the patients undergoing noncurative R2 resection . No difference in survival , either , was observed between the patients treated by R2 resection and those who did not undergo resection . Multivariate analysis identified cytology examination as an independent prognostic factor . CONCLUSIONS Peritoneal washing cytology plays an important role in staging B4 . Positive cytology findings as well as other evidence of disseminated disease may indicate that gastrectomy should be avoided Background We have previously reported the molecular detection of peritoneal micrometastases in patients with gastric cancer by quantifying carcinoembryonic antigen ( CEA ) mRNA in the peritoneal washes . Patients with CEA mRNA exceeding a cutoff value have a significant risk for developing peritoneal carcinomatosis , but optimal treatment for this population remains unknown . Methods CEA mRNA ( + ) patients with gastric cancer were treated postoperatively with S-1 monotherapy .  Overall survival , the primary endpoint of this phase II trial , was compared with the historical control , which is comprised of CEA mRNA ( + ) patients who were not given postoperative chemotherapy . Results A total of 32 patients with CEA mRNA ( + ) gastric cancer were enrolled . Twelve patients ( 37.5 % ) relapsed ; ten showed peritoneal relapse . Three-year survival was similar between the study population and the historical control ( 67.3 % vs. 67.1 % , respectively ) . Conclusions S-1 monotherapy , which significantly reduced risk for recurrence in stage II/III gastric carcinoma in another phase III trial , seems not to be as effective in eradicating free cancer cells in the abdominal cavity The poor prognosis of patients with gastric cancer with free abdominal tumour cells on cytological examination has been described in Japan . In a r and omized trial in the Netherl and s comparing D1 and D2 lymphadenectomy for gastric cancer , patients were subjected to cytological examination of abdominal washings on an optional basis ; findings were of no consequence for scheduled treatment . Cytology results in 535 patients were obtained , in 457 ( 85·4 per cent ) after curative resection and in 78 ( 14·6 per cent ) after palliative operation . There was a clear association of positive cytology results with serosal invasion ( 12 per cent positive cytology ) and lymph node infiltration ( 7·5 per cent positive cytology ) . Survival of those with positive cytology results was significantly lower than that of those with negative findings , irrespective of the procedure employed ( curative or palliative ) . Cytological examination of abdominal washings increases the accuracy of staging and improves the selection of patients suitable for curative or palliative resection Objective : This prospect i ve r and omized multicenter study aims to evaluate the efficacy of extensive intraoperative peritoneal lavage followed by intraperitoneal chemotherapy ( EIPL-IPC ) on the overall 5-year survival of advanced gastric cancer patients with intraperitoneal free cancer cells without overt peritoneal metastasis ( CY+/P− ) . The study also aims to determine the merit and reliability of EIPL-IPC therapy as a prophylactic strategy for peritoneal metastasis . Summary Background Data : Although the prognosis of advanced gastric cancer patients with CY+/P− is extremely poor , a suitable st and ard regimen for treating such patients has not yet been established . Methods : A total of 88 patients with CY+/P− from 1522 patients with advanced gastric cancer at multicenters were enrolled in this study and were r and omly allocated to 3 groups : surgery alone group , surgery plus intraperitoneal chemotherapy ( IPC ) group , and surgery plus EIPL and IPC ( EIPL-IPC ) group . Prognostic significance of EIPL-IPC therapy was evaluated by Kaplan-Meier curves , and its value as an independent prognostic factor was assessed by univariate and multivariate analyses . Results : The overall 5-year survival rate of the patients with EIPL-IPC was 43.8 % , and this data were significantly better than that of the IPC group ( 4.6 % , P < 0.0001 ) and the surgery alone group ( 0 % , P < 0.0001 ) . Among various recurrent patterns , the EIPL-IPC group had a significantly lower incidence of peritoneal recurrence than both of the other groups ( P < 0.0001 ) . Univariate and multivariate analyses revealed that EIPL was the most significant impact factor . Conclusions : The present study clearly revealed that EIPL-IPC therapy significantly improved the 5-year survival span of advanced gastric cancer patients with CY+/P−.  Thus , EIPL-IPC therapy is strongly recommended as a st and ard prophylactic strategy for peritoneal dissemination BACKGROUND Patients with gastric cancer who have positive cytologic results for cancer cells in peritoneal washings ( CY1 ) have poor outcomes , even in the absence of other distant metastases . A st and ard treatment for such patients remains to be established . METHODS We conducted a phase II trial with the 2-year survival rate as the primary endpoint . Patients who had gastric cancer with CY1 status but no other residual disease received postoperative chemotherapy with S-1 ( 1 M tegafur-0.4 M gimestat-1 M otastat potassium ) at a daily dose of 80mg/m(2 ) for 4 weeks , followed by 2 weeks of rest . This cycle was continued until disease progression or intolerable adverse events . D2 dissection was the recommended surgical procedure ; splenectomy could be omitted at the discretion of the surgeon . Accrual of 50 patients was planned , and a 2-year survival rate of more than 36 % was needed to exceed the historical control . RESULTS Forty-eight patients were enrolled , among whom 47 were assessable for survival and 46 for  adverse reactions  . Median overall survival was 705 days , and progression-free survival was 376 days . The 2-year survival rate was 47 % . Median time to treatment failure was 288 days . Neutropenia was the commonest > or = grade 3 toxicity ( 6 patients ) , and anorexia was the most frequent > or = grade 2 non-hematologic toxicity ( 10 patients ) . CONCLUSIONS Gastrectomy followed by S-1 monotherapy result ed in survival that surpassed historical data and can serve as an active control treatment for future trials in patients who have gastric cancer with CY1 status in the Far East BACKGROUND AND OBJECTIVES Free cancer cells in the abdominal cavity exfoliated from a tumor are considered to be responsible for peritoneal dissemination , the most frequent pattern of failure in gastric carcinoma patients treated with curative surgery . METHODS A prospect i ve survival analysis was performed with 91 gastric carcinoma patients treated by potentially curative resection . Cytology was performed for all the patients . The method of Kaplan and Meier was used to construct curves with diagnosis of peritoneal dissemination and cancer death as the end points . Multivariate analysis by Cox 's proportional hazards model was performed to identify independent prognostic factors of significance . RESULTS Patients with a positive cytology result were confirmed to have a greater risk for recurrence in the pattern of peritoneal carcinomatosis and hence a significantly inferior prognosis . Positive cytology was the only significant independent prognostic factor among the curatively resected patients with advanced gastric carcinoma . CONCLUSIONS Peritoneal lavage cytology should be employed for all advanced cancer undergoing potentially curative resection for added accuracy in the stage classification . The results should also reflect the eligibility of the patients for future clinical trials involving perioperative intraperitoneal chemotherapy
Background There is lack of uniformity in the utilization of peritoneal cytology in gastric cancer management .
The identification of intraperitoneal free cancer cells ( IFCCs ) is believed to confer poor prognosis .
However , while some of these patients are palliated , others may undergo more aggressive therapies .
In this review , we aim ed to identify and synthesize findings on the use of peritoneal cytology in predicting peritoneal recurrence and overall survival in curative gastric cancer patients .