Japanese Journal of Clinical Oncology 33:33-37 (2003)
© 2003 Foundation for Promotion of Cancer Research
Long-term Prognostic Value of Conventional Peritoneal Cytology after Curative Resection for Colorectal Carcinoma
Division of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: This study was undertaken to evaluate the long-term prognostic significance of conventional peritoneal cytology in patients with advanced colorectal carcinoma after curative resection.
Methods: A review was performed of 189 patients who underwent curative resection for pT3/T4 carcinoma of the colon and upper/middle rectum between March 1987 and December 1991. Patient outcomes were reviewed retrospectively. Peritoneal cytology was performed before manipulation of the tumor. Intraoperatively, 50 ml of saline were instilled and 20 ml were reaspirated for cytology. In all patients, Papanicolaou and Giemsa stainings were performed to detect intraperitoneal free tumor cells.
Results: The median follow-up was 103 months. Malignant cells were identified in peritoneal washings from 11 patients (5.8%). Of the 11 patients with positive cytology, six (54.5%) developed recurrence and peritoneal recurrence was observed in four (36.4%). In contrast, of the 178 patients with negative cytology, 46 (25.8%) developed recurrence and peritoneal recurrence was observed in four (2.2%). The peritoneal recurrence rate was significantly increased (P = 0.0004) in the patients with positive cytology. The cancer-specific 10-year survival rates for the patients with positive and negative cytology were 45.5 and 80.3%, respectively (P = 0.0051). Multivariate analysis (Cox proportional hazard model) revealed that peritoneal cytology (positive: P = 0.0256) and lymph node metastasis (pN2: P = 0.0004) were independent predictors of cancer-specific survival.
Conclusion: Conventional peritoneal cytology serves as a new prognostic marker after curative resection in patients with advanced colorectal carcinoma. It appears to be a useful diagnostic procedure for predicting recurrence, especially peritoneal recurrence.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Complete removal of the tumor is the most effective primary treatment for carcinoma of the colon and rectum. However, recurrences after curative resection of an apparently localized tumor are inevitable and it is widely accepted that the liver, lung, pelvis and peritoneum are the most common sites of recurrence and metastasis (1). Despite recent advances in the knowledge of various clinical, biological and pathological features that relate to the prognosis of colorectal carcinoma, the degree of tumor penetration into the bowel wall and lymph node involvement have been regarded as the main prognostic factors for patients with colorectal cancer, and these factors are used for prognostic classification in Dukes staging and TNM classification (2,3).
It has been reported that peritoneal cytology can be considered useful for predicting the prognosis of gastric, pancreatic and gynecological malignancies (4–6). Recently, several studies analyzed, in patients with colorectal carcinoma, the incidence of free malignant cells in the peritoneal cavity at the time of surgery and its prognostic significance by means of conventional cytology and immunocytology (7–11).
The aim of this study was to analyze the incidence and the long-term prognostic value of conventional peritoneal lavage cytology after curative resection for colorectal carcinoma at the median follow-up of 103 months.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients
Between March 1987 and December 1991, intraoperative peritoneal lavage cytology was performed in 189 patients who underwent curative resection for pT3/T4 carcinoma of the colon and upper/middle rectum. Only patients with no clinically evident metastatic disease or peritoneal disseminations undergoing planned surgery for curative intent were investigated. Preoperative chemotherapy or radiation therapy was not performed in this series. Follow-up data were obtained for a median observation time of 103 months (range: 2–176 months).
Samples
Immediately after a midline abdominal incision had been made and before manipulation of the tumor, peritoneal lavage cytology was performed. Intraoperatively, 50 ml of saline were instilled into the abdominal cavity over the tumor site and 20 ml were reaspirated for cytology. The lavage solution was immediately centrifuged (1500 r.p.m. for 10 min) and cytological examination was performed after Papanicolaou and Giemsa stainings. The slides were examined by light microscopy by experienced cytologists unaware of the clinical findings. Patients with suspicious morphological evidence of malignancy by microscopy were included in the positive cytology group.
Peritoneal Recurrence
Peritoneal recurrence was defined as radiological or histocytological evidence of cancer recurrence in the abdominal cavity. Liver metastasis, intra-abdominal lymph node metastasis and local recurrence, defined as radiological or histocytological evidence of cancer recurrence at or in the region of primary tumor bed, were excluded.
Statistical Analyses
The clinicopathological parameters such as gender, age, location of tumor, histology, pTNM classification and recurrence between the group with positive and negative cytology were compared using Student’s t test and the Fisher’s exact test as appropriate. Cancer-specific survival curves and disease-free survival curves were estimated using the Kaplan–Meier technique and were compared by means of the log-rank test. For cancer-specific survival, only cancer-related deaths were considered; data on the patients who had died from other causes or who were still alive at the end of the study were censored. To identify independent prognostic factors for survival, statistical analyses were performed using univariate and multivariate analysis. In the univariate analysis, cumulative survival rates were calculated using the Kaplan–Meier method and the differences in the survival curves were compared using the log-rank test. In the multivariate analysis, a Cox proportional hazards model was used to assess the impact of various factors on survival. A P value of <0.05 was considered significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients’ Characteristics
The patients’ demographics are summarized in Table 1. No significant differences were observed regarding the clinicopathological parameters between the groups with positive and negative cytology.
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Prognosis and Type of Recurrence
Disease-free survival rates at 5 and 10 years were both 45.5% for the positive cytology group and 75.6 and 74.3% for the negative cytology group, respectively (Fig. 1). The difference between the two groups was significant (P = 0.0216). Cancer-specific survival rates at 5 and 10 years were 54.5 and 45.5% for the positive cytology group and 85.8 and 80.3% for the negative cytology group, respectively (Fig. 2). The difference between the two groups was again significant (P = 0.0051).
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Recurrences occurred in six of 11 (54.5%) patients with positive cytology and in 46 of 179 (25.7%) patients with negative cytology (Table 1). The rate of peritoneal recurrence was significantly elevated in patients with positive cytology and the details of peritoneal cytology and type of recurrence are summarized in Table 2.
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Independent Prognostic Factors for Survival
Univariate analysis demonstrated that the cancer-specific and disease-free survivals of the patients investigated were significantly related to microscopic peritoneal dissemination and lymph node metastasis (Table 3). Multivariate analysis revealed that lymph node metastasis (pN2: P = 0.0004) followed by peritoneal cytology (positive: P = 0.0256) were independent predictors of cancer-specific survival (Table 4).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Recently, several studies have demonstrated, in patients with colorectal carcinoma, the incidence of free malignant cells in the peritoneal cavity at the time of surgery and its prognostic significance by means of conventional cytology and immunocytology (7–12). On the other hand, Wind et al. (13) reported that conventional cytology provides no prognostic information in Dukes B and C patients and Vogel et al. (14) showed that there was no significant influence of microscopic peritoneal tumor cell dissemination on survival using conventional cytology and immunocytology in patients with colorectal carcinoma who underwent curative resection. However, the numbers of patients registered in these studies (66 and 64, respectively) are clearly limited and the follow-up period of the latter (median follow-up: 44.7 months) was not long enough to draw a definite conclusion. The results of the current study clearly demonstrated that conventional peritoneal cytology influences disease-free and cancer-specific survival after curative resection in patients with pT3/T4 colorectal carcinoma at the median follow-up of 103 months and it appears to be a useful diagnostic procedure to predict recurrence, especially peritoneal recurrence.
In the present study, only conventional peritoneal cytology was chosen as a means to detect cancer cells, because it is a universal and inexpensive method that can be easily performed at any institution worldwide (10). Moreover, the quality of the immunocytological methods on colorectal carcinoma was not fully established during the study period. However, one of the pitfalls of conventional cytology is that peritoneal inflammation can hinder the distinction between malignant cells and atypical or reactive mesothelial cells in body fluids (15,16). In the present study, patients with suspicious morphological evidence of malignancy by microscopy were included in the positive cytology group and it may account for the 45.5% (5/11) ‘false-positive’ rate on recurrence in the positive cytology group. Recently, several studies have demonstrated that immunocytology was more sensitive than conventional cytology for the detection of malignant cells and that it has greater specificity concerning prognosis (7,10,12). Technical advances now permit molecular detection of micrometastasis in lymph nodes and bone marrow in patients with colorectal carcinoma (17–20). Clearly, utilization of these newly developed technologies is indispensable for further investigation.
In summary, this study demonstrated that conventional peritoneal cytology serves as a new prognostic marker after curative resection in patients with pT3/T4 colorectal carcinoma. It appears to be a universal and inexpensive diagnostic procedure to predict recurrence, especially peritoneal recurrence, and would be useful for deciding adjuvant intraperitoneal and/or systemic chemotherapy. However, the utilization of newly developed methods, immunocytology and molecular technology, is necessary in further investigations.
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FOOTNOTES |
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+ For reprints and all correspondence: Seiichiro Yamamoto, Division of Colorectal Surgery, National Cancer Center Hospital, 1–1, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan. E-mail: seyamamo@ncc.go.jp
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REFERENCES |
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Received July 24, 2002; accepted October 17, 2002
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