Peritoneal Recurrence In Patients Research Articles

Risk factors for peritoneal recurrence in serosa-negative gastric cancer.

19 Background: Peritoneal recurrence is often observed in gastric cancer patients without serosal invasion. It is difficult for pathologists to evaluate whether tumor cells penetrate serosa or not, because the subserosa layer is very thin. We evaluated the incidence and risk factors of peritoneal recurrence in serosa -negative gastric cancer patients to clarify the mechanism of peritoneal recurrence in these patients. Methods: A total of 1,745 gastric cancer patients underwent R0 resection from 2002 to 2009 were enrolled. The incidence of peritoneal recurrence according to tumor depth was analyzed. In serosa-nagative patients, the univariate and multivariate analysis were performed to identify the risk factors for peritoneal recurrence. Results: Peritoneal recurrence was observed in 64 (3.7 %) out of 1,745 patients. The incidence of peritoneal recurrence according to depth of tumor invasion was in 0 / 466 in T1a, 5 / 567 (0.88 %) in T1b, 4 / 187 (2.1 %) in T2, 31 / 360 (7.9 %) in T3, 20 / 108 (15.9 %) in T4a, and 4 / 12 (25 %) in T4b, respectively (p<0.001). As for the risk factor for peritoneal recurrence in T3 patients, histologically undifferentiated type, negative lymphatic invasion, scirrhous type, invasive infiltrating growth pattern were the significant factors identified by univariate analysis. Only the invasive infiltrating growth pattern (OR3.44 p0.038) was selected as significant independent risk factor for peritoneal recurrence by multivariate analysis. In T1b / T2 patients, massive lymph node metastasis (N3a, 3b), scirrhous type were the significant factor for peritoneal recurrence by univariate analysis. Only massive lymph node metastasis (OR25.1 p<0.001) was selected as the significant independent risk factor by multivariate analysis. Conclusions: The incidence of peritoneal recurrence increases in proportion to the tumor depth. Invasive infiltrating growth pattern was selected as an independent risk factor for peritoneal recurrence in T3 patients, while it was massive lymph node metastasis in T1b / T2 patients. The results suggest the possibility that microscopic serosal invasion in T3 tumor and lymphatic progression in T1b / T2 tumor may contribute to peritoneal recurrence in gastric cancer.

Intraoperatively assessed macroscopic serosal changes in patients with curatively resected advanced gastric cancer (GC): Clinical implications for prognosis and peritoneal recurrence.

23 Background: To validate the prognostic relevance of macroscopic serosal changes in patients with resected GC, we analyzed prospectively collected databases of two multicenter randomized phase III trials on adjuvant chemotherapy. Methods: In total, 655 patients in the control groups of AMC 0101 (NCT00296322) and 0201 (NCT00296335) trials were selected. Macroscopic serosal changes were determined according to disruptions in serosal continuity, such as changes in color or nodular texture by the operating surgeon. Correlations with recurrence-free survival (RFS), overall survival (OS), and time-to-peritoneal recurrence were analyzed. Results: About two-thirds of the patients were male (69%), and the median age was 55 years (range = 29–70 years). According to Lauren’s classification, 215 patients (33%) showed intestinal type. After a median follow-up period of 61.6 months (range = 2.6–113.9 months), the 5-year RFS and OS rates were 55.0% (95% CI = 51.2–58.9%) and 59.9% (95% CI = 56.2–63.6%), respectively. Intraoperatively assessed macroscopic serosal changes were identified in 432 patients (66%). This was significantly associated with multifocal or diffuse gastric cancer (p = 0.001), Borrmann type IV (p = 0.005), advanced pathological T stage (p < 0.001), advanced pathological N stage (p < 0.001), advanced pathological stage (p < 0.001), and total gastrectomy (p < 0.001). In multivariate analyses, which included prognostic factors of localized gastric cancer, macroscopically serosal changes were significantly associated with poor RFS (hazard ratio [HR] = 2.0, 95% CI 1.4–2.7; p < 0.001) and OS (HR = 2.1, 95% CI 1.5–3.0; p < 0.001). It was also significantly related with shorter time-to-peritoneal recurrence (HR = 2.9; 95% CI = 1.7–5.0; p< 0.001). Conclusions: Intraoperatively assessed macroscopic serosal changes confer a poor prognosis and increased peritoneal recurrence in patients with curatively resected GC. Macroscopic assessment of serosal changes may be a useful indicator that allows better risk stratification of patients with resected GC in terms of prognosis and peritoneal recurrence.

Does preoperative biliary drainage compromise the long-term survival of patients with pancreatic head carcinoma?

The aim of this study was to determine the impact of preoperative biliary drainage (PBD) on long-term survival in patients with pancreatic head carcinoma after surgical resection. Medical records of 160 patients with pancreatic head carcinoma who underwent surgical resection were reviewed retrospectively. Clinicopathological parameters including long-term survival were compared between patients who did and did not undergo PBD. Overall survival of patients who underwent PBD (n = 93) was significantly worse than that of patients who did not (n = 67) by univariate analysis (P = 0.030). However, multivariate analysis revealed that PBD was not an independent prognostic factor for overall survival (P = 0.227). Patients who underwent percutaneous transhepatic biliary drainage (PTBD) had significantly worse survival than patients who underwent endoscopic retrograde biliary drainage (ERBD, P = 0.038) and patients who did not undergo PBD (P = 0.001). The rate of peritoneal recurrence in patients who underwent PTBD was significantly higher than that of patients who underwent ERBD (P = 0.033) or patients who did not undergo PBD (P = 0.034). PBD may not affect the long-term survival of patients with pancreatic head carcinoma if ERBD is used.

Prognostic Value of CEA and CK20 mRNA in the Peritoneal Lavage Fluid of Patients Undergoing Curative Surgery for Gastric Cancer

Peritoneal recurrence is the most common type of recurrence in gastric cancer. Although cytological examination of peritoneal lavage fluid has been used to predict peritoneal spread, peritoneal recurrences often occur even in patients with negative cytology. Our previous retrospective study suggested that reverse transcriptase-polymerase chain reaction (RT-PCR) using peritoneal lavage fluid may be useful for predicting peritoneal recurrence in patients with negative cytology. This prospective study was conducted to validate the clinical impact of this RT-PCR method. From July 2009 to June 2012, a total of 118 cT2-4 gastric cancer patients underwent surgery. Since 14 patients were ineligible because they had incurable factors, the remaining 104 eligible patients were evaluated for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) messenger RNA (mRNA) using RT-PCR. If either CEA or CK20 mRNA was detected by RT-PCR, the patient was defined as PCR-positive as in our previous study. The association between recurrence-free survival (RFS) and background factors was analyzed using Cox proportional hazards models. Of 104 patients, 16 (15.4 %) were positive for either CEA or CK20. PCR-positive patients had significantly worse RFS than PCR-negative patients (log-rank p = 0.007). Regarding the pattern of recurrence, 4 of 16 (25 %) PCR-positive patients and 2 of 88 (2 %) PCR-negative patients had peritoneal recurrence (p < 0.001), but there were no significant differences in recurrence at other sites. Cox multivariate analysis indicated only PCR-positivity as a significant predictor of poor RFS (p = 0.029). This prospective study demonstrated that CEA and CK20 PCR results could predict peritoneal recurrence after curative surgery.

Prognostic information derived from RT‐PCR analysis of peritoneal fluid in gastric cancer patients: Results from a prospective multicenter clinical trial

The purpose of this study is to define the clinical significance of the molecular analysis of peritoneal lavage fluid in patients with gastric cancer in a multicenter prospective trial. Quantitative RT-PCR with CEA and CK-20 mRNA as target markers was introduced for peritoneal lavage diagnosis in 141 patients with clinically advanced gastric cancer from 9 different institutes. We then evaluated the prognostic factors in patients and also evaluated predictive markers for peritoneal recurrence in 124 patients without peritoneal metastasis at surgery Out of the 141 cases, 140 patients were successfully analyzed by RT-PCR of peritoneal lavage fluids. According to multivariate analysis, the combined results of RT-PCR (CEA and CK-20) and CK-20 alone in addition to pathological N (pN)-stage were significantly correlated with overall survival. Multivariate analysis showed that the RT-PCR (CEA and CK-20) and CEA alone in addition to pathological T-stage, pN-stage, and histological grade were significantly correlated with peritoneal recurrence after surgery. This is the first multicenter prospective study to show that RT-PCR analysis of peritoneal lavage fluid with the combination of CEA and CK-20 markers was useful for predicting overall survival and peritoneal recurrence in patients with clinically advanced gastric cancer.

Association of gene expressions of TOP2A, GGH, and PECAM1 with hematogenous, lymph-node, and peritoneal recurrence in patients with stage II/III gastric cancer enrolled in the ACTS-GC study.

4019 Background: Exploratory biomarker analysis was conducted to identify factors related to relapse sites in the ACTS-GC study, a randomized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients (pts) with stage II/III gastric cancer. Methods: Formalin-fixed, paraffin-embedded surgical specimens were retrospectively examined in 829 pts (78.3%), and 63 genes involved in pyrimidine metabolic pathway, growth factor signaling pathway, apoptosis, DNA repair, etc., were analyzed by quantitative RT-PCR after TaqMan assay-based pre-amplification. Gene expression levels were normalized to the geometric mean expressions of GAPDH, ACTB, and RPLP0, used as reference genes. The expression of each gene was categorized as lower or higher than the median value. The impact of gene expression on relapse site was analyzed using the 5-year relapse-free survival (RFS) data of the ACTS-GC. Results: Among the 829 pts, hematogenous, lymph-node, and peritoneal recurrence developed in 72, 105, and 138 pts, respectively. The hazard ratios (HR) (S-1 vs. surgery alone) were 0.79 (95%CI, 0.54-1.16) for hematogenous, 0.51 (95%CI, 0.31-0.82) for lymph-node, and 0.60 (95%CI, 0.42-0.84) for peritoneal recurrence. Among 63 screened genes, topoisomerase II alpha (TOP2A), gamma-glutamyl hydrolase (GGH), and platelet/endothelial cell adhesion molecule 1 (PECAM1) most strongly correlated with hematogenous, lymph-node, and peritoneal recurrence, respectively. Hematogenous RFS was significantly worse in TOP2A high pts than in low pts (HR, 2.35; 95% CI, 1.55-3.57). Lymph-node RFS was significantly worse in GGH high pts than in low pts (HR, 1.87; 95% CI, 1.13-3.08). Likewise, peritoneal RFS was significantly worse in PECAM1high pts than in low pts (HR, 2.37: 95% CI, 1.65-3.41). These factors were independent and stronger risk factors than tumor histological type on multivariate analysis. Conclusions: Expression levels of the TOP2A, GGH, and PECAM1 genes in primary tumors are respectively linked to high risks of hematogenous, lymph-node, and peritoneal recurrence in pts with stage II/III gastric cancer.

Risk factors for peritoneal recurrence in stage II/III gastric cancer patients who received S-1 adjuvant chemotherapy after D2 gastrectomy.

51 Background: Peritoneum is still the most frequent site of the recurrence in stage II/III gastric cancer patients although the survival was improved by S-1 adjuvant chemotherapy. The objective of this retrospective study was to clarify the risk factors of peritoneal recurrence in patients who received S-1 adjuvant chemotherapy. Methods: Peritoneal recurrence free survival (P-RFS) was examined in 100 gastric cancer patients who underwent curative D2 surgery, were diagnosed with stage II or III pathologically, and received adjuvant S-1 between June of 2002 and March of 2011. Uni- and multi- variate analyses were performed to identify risk factors by Cox’s proportional hazard analyses. Results: P-RFS was 64.3% at 3 years and 58.8% at 5 years. A total of 18 patients were diagnosed with peritoneal recurrence. Macroscopic tumor diameter, depth of tumor invasion, and lymph node metastasis were the significant factors by univariate analysis, while tumor diameter and lymph node metastasis were the only significant independent risk factors by multivariate analysis. Conclusions: The macroscopic tumor diameter and lymph node metastasis were the most important risk factors for P-RFS. When patients had these risk factors, S-1 was not sufficient to inhibit peritoneal recurrence. When developing a novel adjuvant chemotherapy targeting peritoneal metastasis in the future, clinical trials should be limited to these patients.

Prevention of Peritoneal Metastases from Colon Cancer in High-Risk Patients: Preliminary Results of Surgery plus Prophylactic HIPEC

The study compared the outcome in patients with advanced colonic cancer at high risk of peritoneal metastases (mucinous or signet-ring cell) without peritoneal or systemic spread, treated with standard colectomy or a more aggressive combined surgical approach. The study included patients with colonic cancer with clinical T3/T4, any N, M0, and mucinous or signet ring cell histology. The 25 patients in the experimental group underwent hemicolectomy, omentectomy, bilateral adnexectomy, hepatic round ligament resection, and appendectomy, followed by HIPEC. The control group comprised 50 patients treated with standard surgical resection during the same period in the same hospital by different surgical teams. Outcome data, morbidity, peritoneal recurrence rate, and overall, and disease-free survival, were compared. Peritoneal recurrence developed in 4% of patients in the experimental group and 22% of controls without increasing morbidity (P < 0.05). Actuarial overall survival curves disclosed no significant differences, whereas actuarial disease-free survival curves showed a significant difference between groups (36.8 versus 21.9 months, P < 0.01). A more aggressive preventive surgical approach combined with HIPEC reduces the incidence of peritoneal recurrence in patients with advanced mucinous colonic cancer and also significantly increases disease-free survival compared with a homogeneous control group treated with a standard surgical approach without increasing morbidity.

Risk Factors for Peritoneal Recurrence in Stage II/III Gastric Cancer Patients Who Received S-1 Adjuvant Chemotherapy After D2 Gastrectomy

The peritoneum is still the most frequent site of recurrence in stage II/III gastric cancer patients, although the survival rate was improved by the introduction of S-1 adjuvant chemotherapy. The objective of this retrospective study was to clarify the risk factors for peritoneal recurrence in patients who received S-1 adjuvant chemotherapy. Peritoneal recurrence-free survival was examined in 100 gastric cancer patients who underwent curative D2 surgery, which were diagnosed with stage II or III disease pathologically, and received adjuvant S-1 between June 2002 and March 2011. The univariate and multivariate analyses were performed to identify risk factors by a Cox proportional hazards analysis. The P-RFS was 64.3% at 3 years and 58.8% at 5 years. A total of 18 patients were diagnosed with peritoneal recurrence. The macroscopic tumor diameter, depth of tumor invasion, and lymph node metastasis were the significant factors identified by the univariate analysis, while the tumor diameter and lymph node metastasis were the only significant independent risk factors identified by the multivariate analysis. The macroscopic tumor diameter and presence of lymph node metastasis were the most important risk factors for peritoneal recurrence. When patients had these risk factors, S-1 was not sufficient to inhibit peritoneal recurrence. A novel adjuvant chemotherapeutic agent targeting peritoneal metastasis in these patients should be developed.

Extensive Intraoperative Peritoneal Lavage as a Standard Prophylactic Strategy for Peritoneal Recurrence in Patients with Gastric Carcinoma

This prospective randomized 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. Although the prognosis of advanced gastric cancer patients with CY+/P- is extremely poor, a suitable standard regimen for treating such patients has not yet been established. A total of 88 patients with CY+/P- from 1522 patients with advanced gastric cancer at multicenters were enrolled in this study and were randomly 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. 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. 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 standard prophylactic strategy for peritoneal dissemination.

Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection

Identification of cancer cells in the peritoneal cavity could influence therapy and outcome of gastric carcinoma patients. The objective of this study was to evaluate the clinical impact of the real-time quantitative polymerase chain reaction-(PCR) based identification of isolated tumour cells in the peritoneal lavage fluid of gastric carcinoma. The peritoneal lavage fluid of 116 patients with gastric cancer was sampled at laparotomy. After RNA extraction and reverse transcription, real-time quantitative PCR was performed using the primers and probes for carcinoembryonic antigen (CEA) and cytokeratin-20 (CK20). When either the CEA mRNA or CK20 mRNA level of the sample was over the cutoff value, the sample was determined to be PCR-positive. Forty-six (40%) of the 116 patients were PCR-positive and 30 (65%) of the 46 PCR-positive patients died as a result of recurrent peritoneal dissemination. The prognosis of the 46 PCR-positive patients was significantly (P<0.001) worse than that of 70 PCR-negative patients. Furthermore, in 80 of the cases with a curative R0 resection, 15 of the patients with PCR-positive findings had a significantly (P<0.001) poorer prognosis than the 65 PCR-negative patients. The prognosis of the PCR-positive patients was significantly poorer than that of the PCR-negative patients in the T3 (P<0.0001) and T4 (P=0.048) subgroups. In a multivariate analysis of the 80 cases with a curative R0 resection, the real-time quantitative RT–PCR (CEA and/or CK20) levels indicated that they were independent prognostic factors. The real-time quantitative RT–PCR analysis of the CEA and/or CK20 transcripts in the peritoneal lavage fluid is useful for predicting the peritoneal recurrence in patients who are undergoing a curative resection for gastric cancer.

A novel rapid genetic diagnosis for peritoneal recurrence in gastrointestinal cancer patients

21052 Background: The prediction of peritoneal recurrence in gastrointestinal cancer patients is extremely important in order to prevent an unfavorable prognosis. The aim of our study was to evaluate the usefulness of a novel rapid RNA amplification system with transcription-reverse transcription concerted reaction (TRC) to detect isolated tumor cells in peritoneal washes of gastrointestinal cancer patients as an intra-operative genetic predictor of peritoneal recurrence. To clarify the characteristic qualities of TRC, we compared the results with those of one-step real-time RT-PCR. Methods: A total of 325 cytology-negative gastrointestinal cancer patients (164 gastric cancer, 161 colorectal cancer) were included. This study was approved by the institutional review board of our hospital and all patients provided written informed consent. Peritoneal washes of Douglas cavity were collected from patients. One-half of each wash was used for cytopathology and the other half was used for molecular diagnosis. Total RNA was extracted from cells which were separated from washes, and TRC and one-step real-time RT-PCR of multiple marker genes (CEA, CK20 mRNA) were performed using a TRCRapid-160 and LightCycler, respectively. Results: The rapidity and simplicity of the TRC is superior to that of one-step real-time RT-PCR. The detection time of marker genes by TRC was only 20 minutes as compared to 70 minutes of real-time RT-PCR. The sensitivity and reproducibility of the TRC were equal to those of real-time RT-PCR. Molecular detection of CEA and/or CK20 transcripts of the peritoneal washes by TRC showed a significant correlation to the depth of invasion, venous invasion, lymph node invasion, lymph node metastasis, peritoneal metastasis and stage. The peritoneal recurrence- free and overall survival rates of CEA and/or CK20 transcript-positive patients were significantly shorter than those of marker gene-negative patients. CEA and/or CK20 transcripts in peritoneal washes were independent prognostic factors of peritoneal recurrence-free survival and overall survival. Conclusion: TRC may be more useful than real-time RT-PCR due to its rapidity and simplicity for the intra-operative genetic diagnosis of peritoneal recurrence in patients with gastric and colorectal cancer. No significant financial relationships to disclose.

EIPL (extensive intraoperative peritoneal lavage) therapy significantly reduces peritoneal recurrence after pancreatectomy in patients with pancreatic cancer

One standing problem in the therapy for pancreatic cancer is peritoneal recurrence after pancreatectomy. We have established EIPL (extensive intra-operative peritoneal lavage) therapy as a very simple and non-aggressive prophylactic treatment for peritoneal dissemination of gastric cancer patients with peritoneal free cancer cells. In this study, the impact of EIPL therapy in preventing peritoneal recurrence in patients with pancreatic cancer after a curative surgical operation is analyzed. This study was based on 39 consecutive patients with invasive ductal adenocarcinoma of the pancreas who underwent curative surgical treatment. The patients were divided into two groups: the non-EIPL group, patients without EIPL therapy (from 1995 to 2000) (n=24); and the EIPL group, patients with EIPL therapy (from 2001 to 2003) (n=15). Clinicopathological findings, recurrence patterns and cancer-free survival were compared between the two groups. In addition, to identify free cancer cells during the operation, both carcinoembryonic antigen (CEA)- and cytokeratin 20 (CK20)-specific intraoperative real-time RT-PCR was performed immediately after laparotomy, lymph node dissection and removal of the pancreas in six patients with curative pancreatic cancer. Peritoneal, hepatic, lymphatic, local, and extra-abdominal recurrence rates in the EIPL and non-EIPL groups were 6.7, 40.0, 26.7, 13.3 and 13.3%, and 45.8, 50.0, 20.8, 29.2 and 20.8%, respectively. Among these recurrence patterns, the peritoneal recurrence rate of the EIPL group was significantly lower than that of the non-EIPL (P=0.013). Real-time RT-PCR analysis identified intra-peritoneal free cancer cells in 0, 33 and 67% of patients immediately after laparotomy, lymph node dissection and removal of the pancreatic cancer, respectively. After EIPL therapy, however, no cancer cell was detected in the peritoneal cavity. EIPL therapy was the independent negative risk factor for peritoneal recurrence (P=0.044), and the cancer-free 2-year survival of the EIPL group showed improvement compared with that of the non-EIPL group and was near statistical significance (P=0.097). EIPL therapy significantly prevented peritoneal recurrence after curative operation of pancreatic cancer, and it may contribute to reducing the mortality rate of this aggressive disease. Continued investigation of this promising treatment regimen is warranted.

Prognostic significance of peritoneal minimal residual disease in gastric cancer detected by reverse transcription-polymerase chain reaction.

A sensitive method for detecting minimal residual disease in the peritoneal cavity by quantifying carcinoembryonic antigen (CEA) mRNA using real-time quantitative reverse transcription-polymerase chain reaction (RQ-RT-PCR) was developed. The clinical value of the method for predicting peritoneal recurrence in patients with gastric cancer was evaluated. A total of 195 patients with gastric cancer and 20 with asymptomatic cholecystolithiasis were included in the study. CEA mRNA expression in peritoneal washings (p-CEA mRNA) was measured by RQ-RT-PCR and normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA expression. The cut-off level of p-CEA mRNA for gastric cancer was determined by examining p-CEA mRNA levels in patients with asymptomatic cholecystolithiasis. Fifty-five (28.2 per cent) of the 195 patients were p-CEA mRNA positive. The rate of p-CEA mRNA positivity correlated significantly with clinicopathological factors. In 163 patients who underwent curative surgery, overall survival and disease-free survival were significantly poorer in p-CEA mRNA-positive patients than in p-CEA mRNA-negative patients (P < 0.001). Cox regression analysis revealed that only p-CEA mRNA was a significant independent prognostic factor (P = 0.034). Multivariate logistic regression analysis showed that p-CEA mRNA was a significant independent risk factor for peritoneal recurrence (P = 0.027). These results suggest that p-CEA mRNA is a reliable prognostic factor and predictor of peritoneal recurrence in gastric cancer.

Prognostic significance of carcinoembryonic antigen levels in peritoneal washes in patients with gastric cancer

Background: Peritoneal metastasis is the most frequent cause of death in patients with gastric cancer. Detection of free cancer cells in the peritoneal cavity at the time of surgery, therefore, is considered to be of great value in predicting the peritoneal recurrence and accordingly in the prognosis in patients with gastric cancer. This study examined the clinical significance of intraoperative determination of carcinoembryonic antigen (CEA) levels in peritoneal washes (pCEA) in patients with gastric cancer. Methods: CEA levels in peritoneal washes were correlated retrospectively with several clinicopathologic factors including clinical outcome in 56 patients with resectable gastric cancer. Results: Among several clinicopathologic factors, the depth of tumor invasion significantly and independently correlated with pCEA levels as revealed by multivariate stepwise logistic regression analysis. A significant difference in overall survival rates was observed between pCEA-positive and pCEA-negative groups: 5-year survival rates were 95.7% in pCEA-negative and 20% in pCEA-positive patients ( P <0.0001). Multivariate analysis indicated that pCEA level is a statistically significant independent prognostic factor for the survival of patients with gastric cancer, and is an important factor for predicting peritoneal recurrence. Conclusions: pCEA could be a potential predictor of a poor prognosis as well as peritoneal recurrence in patients with gastric cancer. We believe that this information could contribute to determining the optimal intraoperative and postoperative therapeutic plan including adjuvant chemotherapy of gastric cancer.

Rapid quantitative detection of carcinoembryonic antigen-expressing free tumor cells in the peritoneal cavity of gastric-cancer patients with real-time RT-PCR on the lightcycler.

Detection of free cancer cells in the peritoneal cavity by RT-PCR using carcinoembryonic antigen (CEA) as a target gene is a more sensitive predictor of peritoneal dissemination than conventional cytology in gastric-cancer patients. Difficulties with this method are the lack of quantitative assessment of free cancer cells and the length of time before completion. To overcome these problems, we have established a rapid and quantitative detection method using a novel real-time fluorescence PCR system (LightCycler). Using this device with hybridization probes as fluorophores, we detected CEA mRNA in peritoneal washes during surgery (within 3 hr) without any post-PCR procedure. This method could reproducibly quantitate 10 to 10(6) CEA-expressing colon carcinoma cells per 10(7) peripheral blood leukocytes, a comparable sensitivity to conventional RT-PCR with a wide dynamic range. Analysis of peritoneal washes from 109 gastric-cancer patients with this assay revealed relative values of CEA transcripts that correlated well with the depth of tumor invasion (p < 0.01). Average values of CEA transcript in peritoneal washes in patients with cytology (-)/RT-PCR(-), cytology (-)/RT-PCR(+) and cytology (+)/RT-PCR(+) results were 0.64, 1,525 and 6,715, respectively. Moreover, CEA transcripts in peritoneal washes in patients with synchronous peritoneal metastasis were more than 50-fold higher than in those without metastasis. These results suggest a positive correlation between CEA mRNA levels in peritoneal washes and prognosis. We conclude that real-time RT-PCR with hybridization probes is a sensitive, quantitative, specific and rapid method to detect free cancer cells in peritoneal washes. This clinically relevant system is a powerful technique to evaluate the risk of peritoneal recurrence in patients with gastric cancer.

Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma

Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma

Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma

The majority of advanced gastric carcinoma patients with serosal invasion die of peritoneal recurrence, even when a curative gastrectomy is performed, because peritoneal recurrence occurs due to intraperitoneal free tumor cells that detach from the serosal-invaded focus. In an attempt to prevent peritoneal recurrence, intraperitoneal hyperthermic chemoperfusion (IHCP) treatment was combined with aggressive surgery. Between March 1987 and December 1996, 141 gastric carcinoma patients with macroscopic serosal invasion were allocated randomly to 2 groups. Seventy-one patients underwent IHCP combined with surgery (IHCP group) and the remaining 70 patients underwent surgery alone (control group). IHCP was performed just after gastric resection and alimentary tract reconstruction under general anesthesia along with systemic hyperthermia. Postoperative complications were reported in 2 of the 71 patients in the IHCP group and in 2 of the 70 patients in the control group. The peritoneal recurrence rate in the IHCP group was significantly decreased (P = 0.0000847) compared with that in the control group. The 2-year, 4-year, and 8-year survival rates for the IHCP group were 88%, 76%, and 62%, respectively, whereas those for the control group were 77%, 58%, and 49%, respectively. The IHCP group thus reaped a significant survival benefit (P = 0.0362) compared with the control group. Although this study was conducted randomly for a small number of patients, compared with the control group, the IHCP group had a high survival rate and better prognosis.

The effect of hypo-osmolar solutions with hibitane on shed cancer cells in peritoneal cavity of patients with gastric cancer

For 100 patients with gastric canvw, intraopemtive intraperitoneal perfusion (IOIPP) using double - distilled water(D. D. W) with hibitane 37°C for 5 mlmge$ was performed. The anticancer effects were assessed cytologically in pre- IOIPP and post-IOIPP specimens of the abdominal effusion and/or iavaged peritoneal fluid. The radical gastrectomy was performed in 65 of 93 cases with advanced gastric cancer, shed cancer cells in peritoneal cavity were detected in 16 of 65 cases with pre- IOIPP (24.62%) and in3 of post- IOIPP cases (4.62%). There was siguificant difftTmce between the two groups (P<0.01). Shed cancer cells were inactivated in vivo estimated by the trypan- blue staining tedmique in 7 cases with rmiicui surgery. But the effect of the IOIPP on shed cancer cells was not significant in cases with peritoneal metastasis. Also there were shed cancer cells in peritoneal cavity of patients with SS cancer histologically before the IOIPP (15.56% ) and iatrogeuic diffmion of cancer cells dm-ing operation (7/24) in this article. The above results indicated that the IOIPP with hypo - osmolar solution containing, hibitane, 37°C for 5 rain was indispensable and useful for the killing of peritoneal shed cancer cells in order to prevent postoperative peritoneal recurrence in patients with radical surgery of advanced gastric cancer regardless of conditiom of serosal invasion.