THE KURUME MEDICAL JOURNAL Vo1. 43, p. 289-294, 1996 ORIGINAL ARTICLE Mucinous Adenocarcinoma of the Stomach Clinicopathological Studies KIKUO KOUFUJI, JINRYO TAKEDA, ATSUSHI TOYONAGA, ISSEI KODAMA, KEISHIRO AOYAGI, SHOJIRO YANO, JUNJI OHTA AND KAZUO SHIROUZU Departments of Gastroenterology and Surgery, Kurume University School of Medicine, Kurume 830, Japan Received for publication August 26, 1996 Summary: The clinical and morphological features of 58 cases of the rare mucinous adenocarcinoma of the stomach (MUC) were investigated and compared to those of other pathological types. The incidence of MUC was only 2.9% of all cases of resected gastric cancer. Among the 58 cases of MUC, the incidence of early cases was only 19% (Group 1), while among other pathological types of cancer, it was 42% (Group 2) (p< 0.001). The incidence of early mucosal cancer was 0% in Group 1, and 54% in Group 2 of the resected early gastric cancer. The incidence of lymph node metastasis rate was 81% in Group 1, and was 46% in Group 2 (p<0.001). The presence of peritoneal dissemination was 21% in Group 1, and was 8% in Group 2 (p< 0.001). The incidence of liver metastasis pre- and intraoperatively was 0% in Group 1, and was 3.5% in Group 2. The overall 5-year-survival rate was 45% in Group 1, and was 61% in Group 2 (p<0.05). In stage III, the 5-year-survival rate was 30% in Group 1, and was 49% in Group 2 (p<0.05). There was no statistical prognostic difference between the two groups in stage I, II and stage IV. Therefore, to improve the outcome for MUC, more effective radical gastrectomy and aggressive immunochemotherapy should be selected, especially for stage III mucinous adenocarcinoma of the stomach. Key words stomach, mucinous adenocarcinoma, gastrectomy, peritoneal dissemination, prognosis Introduction The rare gastric cancer of mucinous adenocarcinoma (MUC) histological type was clinicopathologically investigated retrospectively and compared to other pathological types of resected gastric cancer to discover the characteristics of this unusual type of gastric cancer. Patients an Methods From 1976 to 1995, 1990 cases of gastric cancer underwent resection in the First Department of Surgery, Kurume University Hospital. Among these cases of resected gastric cancer, 58 (2.9%) cases were diagnosed as MUC on the basis of histological examination. The other cases were papillary adenocarcinoma, tubular adenocarcinoma, poorly differentiated 289
29O KOUFUJI ET AL. adenocarcinoma, or a signet-ring cell carcinoma. Remnant gastric cancer, malignant lymphoma, undifferentiated carcinoma, squamous cell carcinoma, carcinoid tumor and leiomyosarcoma were excluded from the present study. In one case of advanced stage IV MUC, marked calcification was observed by X- ray and CT preoperatively. The resected specimens were histologically studied with special reference to the mucin content. Gastric MUC was diagnosed when more than one half the cancer area contained mucin pools. The male to female ratio was 3.1:1, with mean age of 63.1 years, in the MUC group. Total gastrectomy was selected in 20 cases (34.5%), proximal gastrectomy in 3 (5.1%) and distal gastrectomy in 35 (60.4%) cases, in the MUC group. The cancer location, cross-sectional circumference, macroscopic classification, cancer type, cancer depth, and lymph node metastasis rate according to the cancer depth, stage and outcome of these patients were investigated according to the criteria of the Japanese Research Society for Gastric Cancer (1981). The 5-year-survival rate was calculated by the KKaplan-Meier (1958) statistical analysis, and analyzed by the generalized Wilcoxon test. TABLE 1. Number of patients and cancer location A: lower third; M: middle third; C: upper third TABLE 2. Cancer location by cross-sectional circumference Min.: lesser curvature; Maj.: greater curvature; Ant.: anterior wall; Post.: posterior wall; Whole: whole stomach TABLE 3. Number of patients and macroscopic classification Results The stomach can be separated into upper (C), middle (M) and lower (A) portions. The cancer location in each group is given in Table 1, with no statistical difference between the MUC group (Group 1) and the other group (Group 2). With respect to the crosssectional circumference of the cancer lesion, there was a higher incidence of cancer occupying the whole stomach in Group 1 (24%) than in Group 2 (15%) (p< 0.05), as shown in Table 2. The macroscopic classification in each group is summarized in Table 3. Type 0 (early
MUCINOUS GASTRIC CANCER 291 TABLE 4. Number of patients and cancer depth TABLE 8. 5-year-survival rate according to cancer stage TABLE 5. Lymph node metastasis rate according to the cancer depth TABLE 6. Number of patients and lymph node metastasis TABLE 7. Number of patients and cancer stage gastric cancer) was found in only 19% of Group 1 and in 42% of Group 2 (p< 0.001). These included 5 IIc, 3 IIa+IIc, 2 llc+ila and 1 IIa in early MUC. On the other hand, the incidence of type 3 was 41% in Group 1, and was 27% in Group 2 (n<0.05. as shown in Table 3. The cancer depth with number of patients in each group is summarized in Table 4. The incidence of t1 (mucosal cancer+submucosal cancer) was only 19% in Group 1, and was 42% in Group 2 (p<0.001). The incidence of t1 stage mucosal cancer was 0% in Group 1, and was 54% in Group 2 (p<0.001). On the other hand, the incidence of t3 was 52% in Group 1, and was 33% in Group 2 (p< 0.01), as shown in Table 4. The correlation between the lymph node metastasis rate and the small t- factor of cancer depth is summarized in Table 5. The lymph node metastasis rate in t2 was 83% in Group 1 and 48% in Group 2 (p<0.01), and in t3 was 93% in Group 1 and 80% in Group 2 (p<0.05). Absence of lymph node metastasis occurred in 19% of Group 1, and in 54% of Group 2 (p<0.001), as shown in Table 6. The incidence of cancer stage I was 21% in Group 1 and 43% in Group 2 (p< 0.001), as shown in Table 7.
292 KOUFUJI ET AL. The presence of peritoneal dissemination was observed in 21% (12/58) of Group 1 and in 8.3% (152/1932) of Group 2 (p< 0.001), pre- and intraoperatively. However, the incidence of liver metastasis was 0% in Group 1, and 3.5% (63/1932) in Group 2. The MUC can be grossly divided into two groups, well-differentiated and poorly differentiated. The incidence of well-differentiated type was 33% and of poorly differentiated type was 67%. The 5-year-survival rate according to the cancer stage is summarized in Table 8. The 5-year-survival rate was only 45.1% in Group 1 and was 60.5% in Group 2 (p<0.05) overall. The 5-year-survival rate was 46.9% in well-differentiated MUC and was 44.5% in poorly differentiated type. Discussion In recent years, mucin histochemistry has become a very useful complement to the histopathological study of gastric cancer (Bogomoletz, 1988). Biochemically, mucins are complex glycoproteins, consisting of a central core and attached oliogosaccharide side chains. Histochemically, mucins are broadly classified into two groups, neutral and acidic mucins. Acidic mucins are further subdivided into sialomucins and sulfomucins, as described by Geboes et al. (1989). However, there are only few reports of mucinous gastric cancer (Adachi et al. 1991; Kawamura et al. 1994). To discover the characteristics of this rare gastric cancer type MUC, we have investigated clinicopathologically all 58 cases we have resected to date, and compared our findings to those of the more common pathological types of resected gastric cancer. The incidence of MUC was only 2.9% of all resected single gastric cancer in the present study, and was 3.3% as reported by Adachi et al. (1991) and 3.6% by Kawamura et al. (1994). The incidence of early cases in MUC group is especially low, and was only 19% of the resected gastric cancer compared to 42% in the control group of non-muc cases, in the present study. Among these early MUC gastric cancer, the incidence of mucosal early cancer was 0%. All early MUC were s bmucosal cancers. Kawamura et al. (1994) also reported that early cancer was 11.5% in MUC group and was 36.8% in the control group, and that 5 (71%) of the 7 early MUC cancer were mixed macroscopic type such as IIa+IIc and/or IIc+IIa. On the other hand, the mixed type was 45% (5/11) and 45% of IIc in the present study. The location of gastric MUC has been reported to be predominantly in the lower third (A) of the stomach by Kawamura et al. (1994). However, the MUC in our series was located in A and in the middle third of the stomach (M) with equal frequency. According to cross-sectional circumference, the MUC were more frequently in the whole stomach than were the control group. Macroscopically, Borrmann type 3 was predominant in the MUG group compared to the control group in the present study. According to the pathological classification of cancer depth, the incidence of t1 was only 19% in the MUG group and was 41% in the control group. On the
MUCINOUS GASTRIC CANCER 293 other hand, the incidence of t3 was 52% in the MUC group and was 33% in the control group. The overall lymph node metastasis rate in MUC group was 81% and was 45% in control group. Lymph node metastasis was frequently observed in cases of t2 or t3 MUC, in the present study. The overall lymph node metastasis rate in MUC was 80.3% and was 50.9% in a control group reported by Kawamura et al. in 1994. There was no MUC among the 316 cases of mucosal early gastric cancer. The lymph node metastasis rate in submucosal early cancer was 44% (4/9) in MUC and was 17.5% (53/296) over all resected submucosal early gastric cancer, in a previous study (Takeda et al. 1995). When the MUC group was further subdivided into two groups, a well differentiated type and a poorly differentiated type, the incidence of the well differentiated type was 33% (17/58) with a mean age of 67.3 years, while the incidence of the poorly differentiated type was 67% with a mean age of 61.2 years, in the present study. Brander et al. (1974) reported that the mean survival rate was nine years in well differentiated mucoid gastric adenocarcinoma. The prognosis of MUC is also generally good largely since most of these MUC are well differentiated MUC in breast cancer, as reported by Andre et al. (1995). However, there was no statistical difference in prognosis for MUC between the well differentiated type and the poorly differentiated type, in the present study. Peritoneal dissemination (P) was observed intraoperatively in 21% (12/58) in MUC group and in 8% (152/1932) in the control group. Kawamura et al. (1994) also reported that P was in 20% of MUC and in 8% of non-muc. On the other hand, liver metastasis in MUC is very low: the incidence was only 1.6% reported by Kawamura et al., an was 0% in the present study. The characteristics of MUC gastric cancer were a low incidence rate of early cancer and a high incidence rate of lymph node metastasis, advanced stage with large size, deeper cancer depth, a high frequency of peritoneal dissemination, and demonstrating palliative operability compared with other more common gastric cancer types. Therefore, the prognosis of MUC is generally poor: the 5-year-survival rate was 32% to 47% reported by Adachi et al. (1991), Kawamura et al. (1994) and Maruyama et al. (1987). Our overall 5-year-survival rate for MUC was 45.1%. It was 87.5% in stage I, 76.2% in stage II and 10.7% in stage IV, with no statistical difference compared to the control group. However, the 5- year-survival rate in stage III was poor in MUC (29.9%) compared with 49.2% of control (p< 0.05). Therefore, to improve the surgical management of MUC gastric cancer, more effective radical gastrectomy and aggressive immunochemotherapy to prevent peritoneal recurrence should be selected for MUC, especially for stage III mucinous adenocarcinoma of the stomach. References Adachi Y, Mori M, Kido A, Shimono R, Maehara Y et al. A clinicopathologic study of mucinous gastric carcinoma. Cancer 1991; 69:866-871. Brander WL, Needham PRG, and Morgan AD.
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