Motoo Yamagata

Evaluation of serum CEA and CA19-9 levels as prognostic factors in patients with gastric cancer

Background. This clinicopathological study evaluated the utility of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 as predictors of locoregional recurrence and long-term disease-free survival in patients with gastric cancer. Methods. During the period January 1989 to December 1994, 485 patients with primary gastric cancer were evaluated. Gastrectomies were performed in 434 patients. Prognostic factors were analyzed by the Kaplan-Meier method and multivariate analysis, using Cox regression. Results. Elevated serum CEA and CA19-9 levels were observed in 92 of the 485 patients (19.0%), and in 95 of the 435 patients (21.8%), respectively, and both markers were elevated in 29 of these 435 patients (6.7%). Elevated serum CEA and CA19-9 levels correlated well with lymph node metastasis, lymphatic invasion, vessel invasion, stage grouping, depth of invasion, and curability. Patients with elevated serum CEA levels were at significantly higher risk of having all recurrence factors than were those with normal serum CEA levels. Patients with elevated serum CA19-9 levels were at significantly higher risk of having peritoneal metastases and distant metastases than were those with normal serum CA19-9 levels. A significant difference in the cumulative survival curves of patients was demonstrated between those with elevated and those with normal serum CEA or CA19-9 levels, even for patients at the same disease stage (stage III). Patients with elevated levels of both markers had a significantly worse prognosis than patients in whom the levels of both markers were normal. In patients who underwent gastrectomy, elevated serum CEA levels either preoperatively or within 3 weeks after gastrectomy were associated with significantly worse prognosis than were normal levels. When the cutoff level of serum CEA was increased to 10 ng/ml, serum CEA, age, lymph node metastasis, and surgical stage grouping were selected as independent prognostic factors by multivariate analysis of 14 prognostic factors, using Cox regression. Conclusion. Serum CEA and CA19-9 levels provide additional prognostic information in patients with primary gastric cancer. In particular, an elevated serum CEA level provides additional prognostic information and is a useful indicator of curability in patients who undergo gastrectomy. Serum CEA level is an independent prognostic factor in patients with primary gastric cancer.

Gastric cancer in young patients

BACKGROUND Delayed diagnosis, a high rate of histologically undifferentiated types of tumors, and rapid disease progression are frequently cited as the main reasons for the poor prognosis of gastric cancer in young patients. An improved prognosis has been anticipated for young gastric cancer patients because of recent improvements in digestive tract diagnostic techniques. This retrospective study was designed to determine whether these trends have had an impact on young Japanese patients with gastric cancer, and to further elucidate differences in clinicopathologic features between elderly and young patients. METHODS From 1984 to 1995, 1654 patients with gastric cancer were admitted to our hospital. Of these, 86 patients (5.2%) were less than 40 years of age (young group). The clinicopathologic features of this young group were reviewed retrospectively, using hospital records, and compared with those of older patients (n = 499 [29.4%], 60 to 69 years of age). RESULTS The young group contained significantly higher percentages of female patients, epigastric pain symptoms, depressed superficial type lesions, mucosal invasion, and poorly differentiated histology; percentages of hepatic metastasis and venous invasion were lower. Survival rates for all patients and for the resected cases were significantly better in the young group (p = 0.035 and 0.017 respectively). The percentage of early stage stomach cancers for the group less than 40 years of age was 49.0% in 1984-89, but had risen to 60.9% by 1990-95. CONCLUSIONS Early diagnosis has improved the prognosis of young gastric cancer patients. Furthermore, these data show a recent shift in stage distribution; additional prognostic improvement is anticipated for young patients with early gastric cancer.

Bioresorbable membrane to reduce postoperative small bowel obstruction in patients with gastric cancer: a randomized clinical trial.

Objective:This randomized controlled trial was designed to assess whether the use of a sodium hyluronate-based bioresorbable membrane reduces small bowel obstruction after gastrectomy for gastic cancer. Summary Background Data:Clinical studies have reported that a bioresorbable membrane significantly reduces the incidence and severity of adhesion after abdominopelvic surgery. Methods:Between 2003 and 2006, a total of 150 patients with gastric cancer who were scheduled to undergo gastrectomy were randomly assigned to a sodium hyaluronate-based bioresorbable membrane (Seprafilm) group or to a control group. Before closing the abdominal incision, 2 sheets of Seprafilm membrane were applied to the surface of the small intestine under the middle abdominal wound in the Seprafilm group. The primary end point was the incidence of bowel obstruction. Secondary end points were intraoperative and postoperative morbidity and mortality. We registered with Clinical Trials.gov using the Protocol Registration System (ID-NCT00529412). Results:We evaluated a total of 144 patients: 70 in the Seprafilm group and 74 in the control group. The overall incidence (Seprafilm group, 5.7% vs. control group, 9.5%; P = 0.534) and the cumulative incidence of small bowel obstruction (6.2% vs. 12.2% at 36 months; P = 0.3789) were slightly but not significantly lower in the Seprafilm group. The incidence of postoperative complications was similar in the groups (32.9% vs. 29.7%; P = 0.722). Seprafilm did not adversely affect bowel, liver, or renal functions. Conclusions:The use of Seprafilm does not significantly reduce the incidence of small bowel obstruction in patients undergoing gastrectomy for gastric cancer.

Distribution and therapeutic effect of intraarterially transferred tumor-infiltrating lymphocytes in hepatic malignancies. A preliminary report

Indium‐111–labeled tumor‐infiltrating lymphocytes (111In‐TIL) were transferred as an intrahepatic arterial bolus to determine their in vivo distribution in patients with hepatic malignancies. In the in vitro culture system, TIL were expanded upon simultaneous stimulation by recombinant interleukin‐2 (rIL‐2) and immobilized anti‐CD3 monoclonal antibody. This double activation led not only to a larger cell yield, but also to a significantly more dominant subpopulation with CD4+ phenotype than occurred with activation by rIL‐2 alone. Accumulations of 111In‐TIL in the liver were identified by scintigraphy in all of three patients, corresponding to the tumor localization by computed tomography. Such accumulation had persisted for at least 48 hours after infusion. After intraarterial chemoimmunotherapy that included TIL, two of three patients achieved a partial therapeutic response. The authors conclude that their method of culture and transfer can facilitate the accumulation of TIL at tumor sites, which may augment the antitumor effects of adoptive immunotherapy. Cancer 68:2391–2396, 1991.

Apocrine gland carcinoma of the mammary skin concomitant with pagetoid phenomenon

We reported a 52‐year‐old woman with an apocrine gland carcinoma of the mammary skin concomitant with pagetoid phenomenon. She had a 23‐year history of a small nodular lesion on the lower left part of her right breast with a 1‐year history of the pigmented plaque spreading peripherally around the nodule. Our diagnosis revealed that the nodule was an apocrine gland carcinoma and the intraepidermal neoplastic cells with pagetoid spread in the pigmented plaque were derived from the apocrine gland carcinoma. No Paget’s cells were detected in the right nipple, and no tumor cells were observed in the sentinel lymph node and underlying mammary gland tissue. We also investigated the immunohistochemical changes in this case. They showed that both intraepidermal neoplastic cells with pagetoid spread and tumor cells of the apocrine gland carcinoma were positive with cytokeratin‐7 and human epidermal growth factor receptor‐2 (HER‐2)/neu overexpression. The results of the present study conclude that the intraepithelial spread of tumor cells in the mammary skin distant from the nipple occurred as a pagetoid phenomenon, and that HER‐2 may have a key role in pagetoid phenomenon of an underlying apocrine gland carcinoma, as well as in mammary Paget’s disease.