Shinya Terashima

Carbohydrate expression profile of colorectal cancer cells is relevant to metastatic pattern and prognosis

Carbohydrate expression of cancer cells is closely related to the metastatic nature of colorectal cancer. In the present study we investigated the relevance of carbohydrate expression profiles of colorectal cancer cells in the primary lesion to metastatic distribution patterns as well as prognosis in 134 cases. Carbohydrate expression was estimated by histochemistry with 17 kinds of lectins and 3 kinds of Lewis-related monoclonal antibodies (MAbs), and correlations between the staining and clinicopathological parameters were examined. The results showed that lymphatic invasion, lymph node metastasis, and peritoneal metastasis correlated with staining with lectins that bind galactose/N-acetylgalactosamine residues (Gal/GalNAc) such as Maclura pomifera (MPA), Arachis hypogaea (PNA), Helix pomatia (HPA), and Vicia villosa (VVA). In contrast, hepatic metastasis correlated with staining with Anguilla anguilla lectin (AAA), anti-LewisX (LEX-2), anti-sialyl Lewisa (NS19-9), and anti-sialyl-dimeric LewisX (FH-6) MAbs, all of which bind preferentially to fucosylated carbohydrate chains. The five-year survival rate of patients was related to the staining of cancers with MPA, HPA, FH-6 or NS19-9, and MPA- and FH-6 staining were independent prognostic factors. We conclude that carbohydrate expression profiles of cancer cells are relevant to the route of tumor cell dissemination, metastatic pattern as well as prognosis of colorectal cancer.

Overexpression of Fatty Acid Synthase in Oesophageal Squamous Cell Dysplasia and Carcinoma

Objective: The expression of fatty acid synthase (FAS), an enzyme necessary for de novo fatty acid synthesis, has been examined in several types of tumours so far, but not in oesophageal cancer and dysplasia. Methods: We examined the immunohistochemical reactivity of FAS in 4 normal adult oesophagi, 14 dysplastic oesophageal lesions, and 80 squamous cell carcinomas and 6 cases with 4 special types of malignancies of the oesophagus. We also analysed the correlation between FAS expression and various clinicopathological features and long-term survival in patients with oesophageal cancer. Results: In the normal oesophagus, only faint cytoplasmic FAS expression was observed in cells of the basal layer. In contrast, FAS-positive cells were found in 92.9% of cases of dysplasia and 96.5% of cases of carcinoma including 6 cases with a specific histological subtype. However, high expression of FAS did not correlate with either clinicopathological features or prognosis of patients with oesophageal cancer. Conclusion: Our results demonstrate that FAS is expressed in almost all oesophageal carcinomas of both usual and special types and dysplastic lesions, suggesting that FAS may be upregulated continuously from the early stage of oesophageal squamous cell carcinogenesis to established carcinoma.

Sialyl-Tn antigen as a useful predictor of poor prognosis in patients with advanced stomach cancer

Sialyl-Tn antigen (STn) expression was studied immunohistochemically in 211 primary advanced gastric carcinomas. The overall rate of positive STn staining was 17% (35/211), and positive STn staining was found not to be correlated with tumor size, depth of invasion, lymph node metastasis, liver metastasis, or peritoneal metastasis. However, patients with tumors that were immunoreactive for STn demonstrated significantly lower survival (P<0.05). Multivariate analysis revealed that STn staining was an independent prognostic factor. From these findings we conclude that careful followup and intense postoperative therapy are required for patients with advanced gastric cancer who have positive immunoreactivity for STn.

Lymph Node Metastasis-Related Carbohydrate Epitopes of Gastric Cancer with Submucosal Invasion

Abstract This study was conducted to examine the lymph node metastasis-related carbohydrate epitopes of cancer cells in primary lesions of gastric cancer with submucosal invasion (sm gastric cancer). A total of 118 formalin-fixed and paraffin-embedded surgical specimens were studied. Carbohydrate epitopes were de-tected histochemically using 17 kinds of biotin-labeled lectins and three kinds of monoclonal antibodies (mAbs) against Thomsen-Friedenreich antigen (HB-T1), Tn (HB-Tn1), and sialyl Tn antigens (HB-STn1). The node-positive group showed significantly lower reactivities with Ricinus communis I (RCA-I), Lotus tetragonolobus (Lotus), Triticum vulgaris (WGA), and Concanavalia ensiformis (ConA), and higher reac-tivities with HB-STn1. When sm gastric cancer was classified into differentiated and undifferentiated types, lower reactivities with RCA-I and ConA were observed in the differentiated type cancers, whereas lower re-activities with Lotus, WGA, and higher reactivity with HB-STn1 were observed in the undifferentiated type cancers. Nodal status was able to be predicted with high precision by a combination of these carbohydrates and histological subtypes. Since neuraminidase treatment rarely changed the reactivity of cancer cells with these lectins, we conclude that the loss of certain kinds of carbohydrates that are restricted by histological subtypes is related to lymph node metastasis in sm gastric cancer.

SOYBEAN AGGLUTININ BINDING AS A USEFUL PROGNOSTIC INDICATOR IN STOMACH CANCER

Soybean agglutinin (SBA)-binding carbohydrate expression was studied immunohistochemically in 353 primary gastric carcinomas. The overall rate of positive SBA staining was 23% (81/353), and positive SBA staining was significantly correlated with tumor size, macroscopic tumor type, depth of invasion, lymph node metastasis, and venous invasion (P < 0.05). Moreover, patients with tumors that were immunoreactive for SBA demonstrated significantly higher survival (P < 0.01). From these findings we conclude that careful follow-up and intense postoperative therapy are required for patients with gastric cancers that lack immunoreactivity for SBA.

An improved technique for low anterior resection using a PDS endoloop

We describe herein the results of performing a new technique of low anterior resection of the rectum using a PDS endoloop, on ten patients with rectal cancer. This technique involves first preparing the rectosigmoid colon with an anvil as in the conventional low anterior resection; then, after the stapler is inserted transanally, two endoloops are slid over the colon and rectum. The rectum is ligated by pushing the knot of the endoloop and a second knot is applied 2 cm proximal to the first. Finally, the rectum is cut and the stapler is closed and fired to make a circular end-to-end anastomosis. The level of the anastomosis ranged from 2.5 to 6 cm with a mean of 4.7 cm in the ten patients, only one of whom developed a minor anastomotic leakage postoperatively. Moreover, no patient has developed local recurrence or distant metastasis to date. In summary, this technique offers certain advantages that allow the operation to be done with more skill and safety in a narrow pelvis.

Wheat germ agglutinin binding is a useful prognostic indicator in stomach cancer

AbstractBackground. Recent studies suggest that lectin binding activity is correlated with the metastasis and prognosis of several human carcinomas. Wheat germ agglutinin (WGA) is a lectin that recognizes mainly N-acetyl-glucosamin (GalNAc) and acetyl-neuramic acid. However, little is known about WGA expression in gastric carcinoma. The purpose of this investigation was to clarify the significance of WGA expression in human gastric carcinoma. Methods. WGA binding was examined immunohistochemically in 353 specimens of primary gastric carcinomas from patients surgically treated at the First Department of Surgery, Fukushima Medical School, between 1980 and 1990. We studied the relationship between WGA expression and various clinicopathologic features and long-term survival. Results. Overall, 145/353 of the tumors (41%) were stained for WGA. WGA expression correlated with mean patient age, lymph node metastasis, venous invasion, and liver metastasis. Patients with tumors that were nonimmunoreactive for WGA had significantly lower 5-year survival rates than those with immunostained tumors (P < 0.05). WGA expression emerged as an independent prognostic factor on Coxs multivariate analysis. Conclusion. WGA binding is a useful prognostic indicator. Careful follow-up and intensive postoperative therapy are required for patients with gastric carcinomas that are nonimmunoreactive for WGA.

Prognostic role of immunosuppressive acidic protein in patients with esophageal cancer

Immunosuppressive acidic protein (IAP) suppresses several immune responses in vivo and in vitro , and high preoperative IAP levels could predict the impairment of the hosts immunity. In this study prognostic significance of preoperative IAP levels was investigated in 68 esophageal cancer patients with curative resection and eight with non-curative resection. The curative group had significantly lower levels than the non-curative group (432 +/- 183 mg/mL vs. 739 +/- 235 mg/mL, P < 0.0001). The IAP levels were associated with T-status (P < 0.0001), lymphatic invasion (P < 0.05), and p-stages (P < 0.0001). When 5-year survival rate of patients with curative resection was compared by setting various cutoff values of IAP between high and low IAP groups, several cutoff points (400-580 mg/mL) were revealed to be significantly associated with survival. Setting cutoff value of IAP to 560 mg/mL resulted in a most significant difference of 5-year survival rate of patients between the high and low IAP groups (13.9% and 61.5%, P < 0.0001). These data indicate that pre-operative IAP level is a useful parameter to predict the prognosis of esophageal cancer patients after curative resection.

Recent indications and methods of surgery for inflammatory bowel disease.

Inflammatory bowel disease, notably ulcerative colitis (UC) or Crohn disease (CD), is basically benign, but sometimes develops into serious or fatal cancer. While the primary therapies are medical, such as pharmacotherapy and dietetic modification, intractable, serious, and cancerous cases can require surgical intervention. Surgery represents only one of the treatment options, but prediction of whether UC and CD are likely to progress to serious conditions and determination of when to undertake surgery is essential. Various surgical procedures have been developed over time, and the postoperative results are now generally good. Regarding laparoscopic surgeries, relatively few cases have been accumulated, and addressing the indications and limitations is premature at this point. However, this procedure is likely to fulfill a central role in surgical treatment strategies and represent a major benefit to patients. This paper discusses surgical treatment indications and methods for UC and CD, and explains the practical aspects of laparoscopic surgery, which has made remarkable progress in recent years, for such cases.

CASE REPORT: Development of Acute Mesenteric Artery Thrombosis Five Years After Total Gastrectomy: Reconstructive Surgery

A 68-year-old woman was referred to the emergency room with acute onset of severe abdominal pain and hematemesis. The patient had a history of stomach cancer which was treated in 1994 by total gastrectomy with splenectomy and retrocolic esophagojejunostomy by Rouxen-Y reconstruction. Postoperative TNM classification was Stage IA disease (T1N0M0). The patient also had a long history of hypertension and sick sinus syndrome for which a permanent pacemaker was implanted in 1994. On admission, she looked pale and unwell. The body temperature was 36.3°C, the pulse rate was 122 bpm, and respiration was fast, at 24/min. Arterial blood pressure was 80/40 mm Hg. Physical examination showed distension and rigidity of the entire abdomen, with marked tenderness. An erect chest radiograph was normal, showing no free subdiaphragmatic gas, but supine abdominal radiograph suggested mucosal edema of the small intestine. Upper endoscopic examination showed ischemic mucosa with oozing from the jejunum at the site of esophagojejunostomy, consistent with acute mesenteric infarction. Laboratory tests showed the following abnormal values: white blood cell count, 16,300/ mm; hematocrit, 49.6%; C-reactive protein, 1.3 mg/dl; serum creatinine, 1.1 mg/dl; pH, 7.312; and base excess, 11.0. An electrocardiogram showed the presence of atrial fibrillation. Under the provisional diagnosis of acute superior mesenteric ischemia, an emergency operation was performed. At laparotomy, 300 ml of turbid blood-stained ascites was noted. The small intestine was gangrenous from the esophagojejunostomy junction and involving the entire small intestine and cecum. The jejunal portion from the ligament of Treitz to 30 cm distally was normal and viable. The small bowel from the site of esophagojejunostomy to the terminal ileum and cecum was distended and dark in color (Figure 1A). No peristalsis or arterial pulsations were noted. The necrotic bowel segments were resected. Due to the critical condition of the patient and borderline viability of the remaining part of the small intestine, with potential risk of impaired healing of the anastomosis and further gangrene, reconstruction was not performed. The esophagus was transected using a linear stapler as a stump within a nasogastric tube suction. The ascending colon was transected at a viable portion with a linear stapler. Then the jejunum was transected at 30 cm distal from the ligament of Treitz. A decompression drainage tube was inserted from the stump of the jejunum and placed near the ligament of Treitz (Figure 1B). Finally, a sump drain was placed deep within the left subphrenic space and exteriorized through a stab wound. The pathological diagnosis was hemorrhagic necrosis of the intestine with mesenteric arterial thrombosis. A second operation was planned at an early postoperative period after restoration of general condition. However, during the postoperative period, the patient developed pneumonia, which required treatment for 12 days. On the sixth postoperative day, a saliva-like purulent discharge was drained from the left subphrenic drain, suggesting major insufficiency of the esophageal stump. On the 12th postoperative day, a second operation was performed for reconstruction. Severe and diffuse intraabdominal adhesions were present. Although the esophageal stump had a major leakage, the superior and inferior mesManuscript received March 23, 2001; revised manuscript received December 4, 2001; accepted January 28, 2002. From the First Department of Surgery, Fukushima Medical University, Fukushima 960-1295, Japan. Address for reprint requests: Dr. Shinya Terashima, First Department of Surgery, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan. Digestive Diseases and Sciences, Vol. 47, No. 7 (July 2002), pp. 1511–1513 (© 2002)