Tsutomu Kaetsu

Gastric and Intestinal Phenotypic Marker Expression in Early Differentiated-Type Tumors of the Stomach: Clinicopathologic Significance and Genetic Background

Purpose: Gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. In the present study, we determined the clinicopathologic significance of phenotypic marker expression in early-stage gastric differentiated-type tumors and the association between marker expression and genetic alterations. Experimental Design: Phenotypic marker expression was determined by examining the expressions of human gastric mucin (HGM), MUC6, MUC2, and CD10 in 63 gastric adenomas, 133 early differentiated-type carcinomas, and 24 follow-up cases with gastric adenoma. Tumors were classified into gastric, gastric and intestinal mixed, or intestinal phenotypes according to the immunopositivity of the above markers. The presence of mutations in APC, K-ras, and p53 and the microsatellite instability status were also determined in all tumors. Results: The expressions of HGM and MUC6, representing gastric or gastric and intestinal mixed phenotypes, were significantly associated with high-grade atypia in the 63 gastric adenomas. Among the 133 early differentiated-type carcinomas, HGM expression was significantly associated with mixed-type (with an undifferentiated-type component) tumors and lymph node metastasis. MUC2 expression was inversely associated with submucosal invasion. A multivariate analysis revealed that gastric adenomas were significantly associated with the intestinal phenotype and were inversely associated with p53 mutation compared with early differentiated-type carcinomas. Among all 196 tumors, APC mutation was significantly associated with CD10 expression and the intestinal phenotype and was inversely associated with the expressions of HGM and MUC6. The microsatellite instability status was significantly associated with MUC6 expression. Malignant transformation from gastric adenoma to carcinoma was shown in 5 of the 24 follow-up cases of gastric adenoma. The malignant transformation was significantly associated with the gastric and intestinal mixed phenotype and was inversely associated with APC mutation. No malignant transformation was found in intestinal phenotype gastric adenomas with APC mutation. Conclusions: Our present findings show that phenotypic marker expression is associated with tumor aggressiveness during the early stage of gastric differentiated-type tumors. Differences in the biological behavior of tumors with different phenotypes may result from differences in the genetic backgrounds during the incipient phase of gastric tumorigenesis.

Gastric and intestinal phenotypic cell marker expressions in gastric differentiated-type carcinomas: association with E-cadherin expression and chromosomal changes

AbstractsGastric and intestinal phenotypic cell markers are widely expressed in gastric carcinomas, irrespective of their histological type. In the present study, the relations between the phenotypic marker expression of the tumour, histological findings, expression of cell adhesion molecules, and the chromosomal changes in gastric differentiated-type carcinomas were examined. The phenotypic marker expression of the tumour was determined by the combination of the expression of the human gastric mucin (HGM), MUC6, MUC2 and CD10, and was evaluated in comparison with the expression of cell adhesion molecules, such as E-cadherin and β-catenin, and chromosomal changes by comparative genomic hybridization (CGH) in 34 gastric differentiated-type carcinomas. Tumours were classified into the gastric- (G-), gastric and intestinal mixed- (GI-), intestinal- (I-), or unclassified- (UC-) phenotype according to the immunopositivity of staining for HGM, MUC6, MUC2, and CD10. G-phenotype tumours were significantly associated with a higher incidence of differentiated-type tumours mixed with undifferentiated-type component, compared with GI- and I-phenotype tumours (88.9 vs 33.3%, P=0.0498 and 88.9 vs 42.9%, P=0.0397; respectively). HGM-positive tumours were significantly associated with a higher incidence of tumours with abnormal expression of E-cadherin, compared with HGM-negative tumours (66.7 vs 21.1%, P=0.0135). GI-phenotype tumours were significantly associated with a higher incidence of tumours with abnormal expression of E-cadherin, compared with I-phenotype tumours (77.8 vs 21.4%, P=0.0131). HGM-negative tumours were significantly associated with higher frequencies of the gains of 19q13.2 and 19q13.3, compared with HGM-positive tumours (57.9 vs 20.0%, P=0.0382 and 63.2 vs 13.3%, P=0.0051; respectively). MUC6-positive tumours were significantly associated with higher frequencies of the gains of 20q13.2, compared with MUC6-negative tumours (71.4 vs 30.0%, P=0.0349). MUC2-positive tumours were significantly associated with the gain of 19p13.3, compared with MUC2-negative tumours (41.2 vs 5.9%, P=0.0391). I-phenotype tumours were significantly associated with higher frequencies of gains of 5p15.2 and 13q33-34, compared with G-phenotype tumours (66.7 vs 0%, P=0.0481, each) and also associated with higher frequencies of gain of 7p21, compared with GI-phenotype tumours (66.7 vs 0%, P=0.0481). Our present results show that gastric differentiated-type carcinomas have different characteristics according to the phenotypic marker expression of the tumour in terms of histological findings, E-cadherin expression and pattern of chromosomal changes.

Minimally invasive treatment of stomach cancer.

The rate of detection of early gastric cancer has increased because of the development of diagnostic techniques, such as endoscopy, biopsy, and endoscopic ultrasonography. Recently, minimally invasive surgical procedures for benign gastric conditions have been advocated, and the laparoscopic approach is noted as a technique that increases the quality of life. However, the development of laparoscopic gastric resections and laparoscopically assisted gastric operations for malignancy still deserve a word of caution. Laparoscopic local resection of the stomach is used to treat mucosal cancer without lymph node metastasis, and laparoscopy-assisted distal gastrectomy is used to treat early gastric cancer with lymph node metastasis in the perigastric portion. According to short-term results reported by a small group of surgeons, laparoscopic approaches for gastric cancer result in a minimally invasive approach, early recovery, and decreased morbidity and mortality. However, the longterm results of these less invasive treatments are not known in advanced gastric cancer. If the results of randomized controlled studies for advanced gastric cancer are confirmed, the use of these techniques will spread worldwide and may become a standard technique for the resection of gastric cancer.

Successful curative resection of gastric cancer with AIDS infection

This report describes the case of a 47-year-old Japanese man with human immunodeficiency virus (HIV) infection with AIDS, who was successfully treated for gastric cancer. A review of gastric cancer associated with HIV is also presented. Prior to surgical treatment, azidothymidine (AZT), nerfinavir (NFV), and lamivudine (3TC) were administered to the patient in order to improve his blood CD4 count and reduce the viral burden. Consequently, distal gastrectomy was performed as a curative resection without any complications. The gastric cancer included a signet-ring cell carcinoma, as was noted in eight of the nine reported cases associated with HIV. This suggests that the HIV virus may play a role in causing signet-ring cell carcinoma, especially in the stomach.

The Indications of Proximal Gastrectomy for Gastric Cancer in the Upper Third of the Stomach.

過去44年間に当教室で切除された上部胃癌 (C, CM, CE) 318例を対象とし, 噴門側胃切除術の適応について検討した. 各深達度別のリンパ節転移の割合はm: 0% (0/23), sm: 6.1% (2/33), mp: 25% (4/16), ss: 74.1% (43/58), se: 81.3% (104/128), si: 91.7% (55/60) で, ss以上でリンパ節転移が高率であったが, mp以深ではリンパ節転移112までであった. またsm, mp癌の転移リンパ節の詳細はsmがNo1, 7, mpがNo1, 2, 3, 11で, No4d, 5, 6, 10に転移を認めなかった. 治癒切除後の再発形式でも深達度mpまでの癌でリンパ節再発を認めたものはなく, 深達度mpまでの5年生存率でも噴切群86.7%に対し全摘群74%と両群間に差を認めなかった. 以上よりC領域の早期胃癌においてはD1+No7, mp癌においてもD1+No7, 11の郭清を加えることにより噴切は適応となる. 深達度ss以深ではn2以上の転移が高率であり噴切の適応とはならず, 拡大郭清が適応となろう.

A case of ruptured aneurysm of the left gastric artery with early gastric cancer.

症例は70歳男性.言語・構音障害を主訴に当院入院.左側頭葉に血腫を認め, 保存的治療を行っていたが, 突然, 出血性ショックに陥り, 厳重な全身管理下に出血源精査を行った.上部消化管内視鏡検査では胃体上部にIIc型早期胃癌を認めたが, 出血源とは断定できず, 腹部超音波検査および腹部computed tomography検査を行った.肝下面を中心とする腹腔内血腫が認められ, 腹部血管造影検査を行い左胃動脈瘤の存在を認めたため, 早期胃癌を併存した左胃動脈瘤破裂と診断し, 胃全摘術を施行して救命しえた.本症は, 調べえた本邦報告例では10例とまれであり, かつ破裂例は6例のみであった.画像診断, 全身管理の進歩により, 近年予後の改善をみているが, いまだ診断に難渋している症例が多かった.原因不明の腹痛, 急激なショックを呈した症例に遭遇した際には本症も念頭に置くべきと思われた.