We report two cases of unresectable advanced gastric cancer treated with S-1, CDDP and trastuzumab. A significant reduction of tumors was observed in these cases. A 77-year-old man was diagnosed as unresectable gastric cancer. The pathological diagnosis was tub2 and human epidermal growth factor receptor 2(HER2)positive(3+IHC method). We started chemotherapy(S-1+CDDP+trastuzumab). After 2 courses of S-1+CDDP, the findings of upper gastrointestinal endoscopy and CT were much improved to PR. But after 6 courses of S-1+CDDP, they worsened to PD. The regimen of chemotherapy was changed to weekly paclitaxel. The other patient, a 68-year-old woman, was diagnosed as far advanced gastric cancer. The pathological diagnosis was tub2=por2 and HER2 positive(3+IHC method). We started chemotherapy(S- 1+CDDP+trastuzumab). After 3 courses of S-1+CDDP, the tumor reduced significantly to PR. We continued this regimen. From the result of the ToGA trial, addition of trastuzumab to chemotherapy(capecitabine+CDDP or fluorouracil+CDDP) has been recommended as a new standard first-line regimen for HER2-positive advanced gastric cancer. But there is no evidence that trastuzumab added to the other regimen improved survival in patients with advanced gastric cancer. It is necessary to conduct a clinical trial to evaluate the treatment effect of this chemotherapy.

症例は76歳，女性．平成16年3月，直腸癌にて低位前方切除術施行．病理組織学的所見は中分化腺癌，ss，n0，P0，H0，M(－)，stageII．術後は化学療法せず，外来で経過観察されていた．平成17年7月，CEA 5.4ng/ml，10月には8.0ng/mlと上昇を認めた．CT上明らかな異常所見なく，FDG-PET/CT施行．小腸にFDGの集積を認め，MRI上も同部位の小腸壁に肥厚が認められた．直腸癌術後小腸転移の診断で，11月手術施行．腹膜播種はなく，Bauhin弁より約20cm口側回腸に腫瘤あり，小腸部分切除術施行．病理組織学的所見で中分化腺癌が認められ，前回直腸癌と同様の所見であることから，直腸癌術後孤立性小腸転移と診断された．術後TS-1を隔日投与し，再発巣切除術後3年3カ月経過した現在無再発生存中である．

Extramedullary plasmacytoma (EMP) of the gastrointestinal tract is an uncommon-type of neoplasms. This report describes a case of EMP in the small intestine. A 78-year-old male, with abdominal discomfort and vomiting, was found to have a 7-cm sized tumor of the small intestine and swollen lymph nodes. He underwent resection of the bowel and lymph nodes. Histological examination of the resected specimens revealed compact tumor cells from mucosa to subserosa and infiltrate into the fat tissue of the mesentery and the lymph nodes. Pathological examination of the resected specimen revealed plasma cell-like round cells, Dutcher bodies, and Russell bodies. Immunohistochemical examination showed that the cytoplasm of the tumor cells were positive for CD138 and the nuclei were positive for cyclin D1. Four months after surgical resection, the patient had recurrence of tumor cells in the para-aortic lymph nodes and lumbar vertebrae. Chemotherapy treatment was ineffective. Surgical resection followed by chemotherapy is thought to be effective in the case of intestinal obstruction, although there is a possibility of devastation which is resistant to chemotherapy. We propose that tumor cells positive for cyclin D1 may play a key role in devastation and could be a useful indicator of prognosis.

症例は64歳,男性.突然気分不快,冷汗出現したが軽快せず,救急車にて来院.来院時収縮期血圧70mmHgまで低下し,ショック症状を呈していた.胸腹部CT施行にて,腹水の貯留,胃角部背側に動脈瘤を認め,また腹腔穿刺にて血性腹水を確認し,動脈瘤破裂による出血性ショックと診断した.昇圧剤使用後も血圧は上昇せず,緊急手術に踏み切った.開腹時,腹腔内には約3,000mlの血液がみられ,凝血塊が左胃動脈瘤を中心に腹腔内に広がっていた.動脈瘤を切除し,手術を終了した.術後は順調に回復,第17病日に限院となった.摘出標本の病理組織所見では, Segmental arterial mediolysis (SAM)による左胃動脈瘤破裂と診断された.腹部内臓動脈瘤は比較的稀な疾患であり,近年この成因にSAMという概念が提唱されている.今回,われわれはSAMによる左胃動脈瘤破裂の1例を経験したので報告した.

1996年1月から2006年5月まで当院で十二指腸潰瘍穿孔の診断を受けた32例を手術選択群14例, 保存的治療選択群18例 (うち完遂群14例, 手術移行群4例) に分け, それぞれの臨床的特徴を検討するとともに, 保存的治療の妥当性について検討した。手術選択群は保存的治療選択群とくらべ発症から来院までの時間が長く, 来院時腹部CT検査での腹水貯留部位数が多かった。保存的治療選択群では, 入院翌朝の腹水貯留部位数が保存的治療完遂群で入院時と不変もしくは減少したのに対し, 手術移行群では入院時より増加していた。また入院翌朝までに腹痛の軽減を認めたのは完遂群が全例であったのに対し, 手術移行群ではわずか1例であった。手術移行群の開腹所見では被覆されていた潰瘍穿孔は1例もなく, 手術は妥当であったと考えられた。保存的治療選択群で重篤な合併症や死亡例はなく, 保存的治療の選択およびその後の判断も妥当であったと考えられた。

We report the result of trafermin treatment of a colocutaneous fistula refractory to non-surgical management. Trafermin, also known as recombinant human basic fibroblast growth factor, is a topical therapeutic drug that stimulates angiogenesis and accelerates granulation. The case described here is that of a 67-year-old male patient who developed a colocutaneous fistula following surgery for a tumor of the lower rectum. Standard non-surgical techniques were ineffective in closing the fistula. Trafermin treatment resulted in a gradual reduction in exudate from the wound, and radiological examination 10 days after the introduction of trafermin showed the fistula had healed. Subsequent infection of the wound site was also successfully treated using trafermin. Injection of trafermin into a colocutaneous fistula tract thus shows promise in the management of fistulas refractory to non-surgical therapies.

Peritoneal metastasis is an important prognostic factor in cases of gastric cancer. Although studies on comparative genomic hybridization (CGH) in gastric cancer have been reported, there are few reports on the peritoneal metastasis (P) and peritoneal cytology (CY) factors in this cancer. In this study, we analyzed the chromosomal changes in the primary tumor with a combination of laser microdissection analysis and CGH in an attempt to detect the unknown abnormal chromosomal regions. We analyzed 34 primary tumors, including 13 primary tumors with peritoneal metastasis (P1) and/or positive peritoneal cytology (CY1) using a combination of laser microdissection and CGH. The minimal overlapping regions in gains were assigned to 5p14 (46.2%), 7q21.3 (61.5%), 7q31 (46.2%), 7q36 (46.2%), 8q23 (53.8%), 15q26 (46.2%), 20q12 (61.5%), 20q13.1 (53.8%), and 20q13.2 (53.8%) in primary tumors with P1 and/or CY1. The minimal regions of losses that occurred most frequently were 4q34-q35 (23.1%) and 22q11.2 (23.1%). There were significant differences in the minimal regions of 5p14 (P=0.033), 7q21.3 (P < 0.0001), 7q31 (P=0.013), 7q36 (P=0.033), and 22q11.2 (P=0.048) between primary tumors with and without P1 and/or CY1. In this study, gain/amplification of 5p14, 7q21.3, 7q31, and 7q36, and loss of 22q11.2 were significant in gastric cancer cases with peritoneal dissemination and/or positive peritoneal cytology.

近年早期胃癌に対する腹腔鏡補助下幽門側胃切除は多くの施設で行われている。しかし, D2リンパ節郭清を伴う腹腔鏡補助下幽門側切除は容易とは言えない。腹腔鏡下D2リンパ節郭清では小彎側のリンパ節郭清前に十二指腸切離を先行して行う報告が多い。教室では手技上の工夫として十二指腸切離を先行しない腹腔鏡下D2リンパ節郭清を経験したので症例と手技の要点について報告する。症例1 : sType0 IIc+III, sT2 (MP), sN0, sStage I B, 症例2 : sType0 IIc, sT1 (SM), sN0, sStage I A。手技の要点はすべてのリンパ節郭清を腹腔鏡下に終了後, 十二指腸切離を小開腹創より行う。本術式を2例経験したので若干の文献的考察を加え報告する。

Both gastric and intestinal phenotypic markers are known to be expressed in gastric carcinomas, irrespective of their histologic type. In the present study, the relation between gastric and intestinal phenotypic marker expression in gastric carcinomas and the recurrence pattern after surgery was examined. The phenotypic marker expression of the tumour was determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2 and CD10 in 213 advanced gastric carcinomas in 213 patients who had undergone a curative resection (97 died from recurrent gastric carcinoma and 116 were alive without recurrence at the end of the follow-up period). Tumours were classified into gastric (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC) phenotypes according to the immunopositivity of HGM, MUC6, MUC2 and CD10 stainings. The incidence of HGM-positive tumours and MUC2-negative tumours was significantly higher in tumours with peritoneal recurrence than in tumours without recurrence (73.3%, 44 out of 60 cases vs 54.3%, 63 out of 116 ( P =0.022); and 70.0%, 42 out of 60 vs 38.8%, 45 out of 116 ( P =0.0002), respectively). The incidence of G-phenotype tumours was also significantly higher in tumours with peritoneal recurrence than in tumours without recurrence (58.3%, 35 out of 60 cases vs 28.4%, 33 out of 116 ( P =0.0002)). The incidence of MUC2-negative tumours and CD10-positive tumours was significantly higher in tumours with haematogenous recurrence than in tumours without recurrence (62.5%, 20 out of 32 cases vs 38.8%, 45 out of 116 ( P =0.028); and 43.8%, 14 out of 32 vs 23.3%, 27 out of 116 ( P =0.039); respectively). Our present findings show that the gastric and intestinal phenotypic marker expression of the tumour, determined by immunohistochemical staining for HGM, MUC6, MUC2 and CD10, can be used to predict the pattern of gastric carcinoma recurrence after curative resection.

教室の過去のLおよびM領域の単発SM胃癌切除例(n=258)のリンパ節転移,再発形式より, SM胃癌の至適リンパ節郭清について検討した.リンパ節転移はpN0 79.8%, pN1 16.3%, pN2 3.1%, pN3 0.8%であった. pN2症例にNo.11p, 12a, 14v転移は認めなかった.多変量解析で有意差を認めた予後因子はリンパ節転移と静脈侵襲の有無であり,リンパ節郭清程度は有意ではなかった.再発形式は血行性再発が60%と最多であり, pN0, pN1例の再発死亡は各3例でリンパ節再発は認めなかった.また, sN0例に再発は認めず, sN1例にリンパ節再発は認めなかった.以上より, sT1 (SM), sN1例に対する,ガイドラインで推奨されている現規約D2郭清による予後改善の可能性は低いことが示唆された.

Purpose. It is well known that both gastric and intestinal phenotypic markers are expressed in gastric carcinomas, irrespective of their histological type. In the present study, the associations among phenotypic marker expression of gastric carcinomas, tumor thymidylate synthase (TS) expression, and the chemotherapeutic response to 5-fluorouracil (5-FU) were examined. Methods. The gastric and intestinal phenotypic marker expression of the tumor was determined by the combination of the expression of human gastric mucin (HGM), MUC6, MUC2, and CD10, and was evaluated in comparison with tumor TS expression in 137 advanced gastric carcinomas in 137 patients (75 with postoperative chemotherapy with 5-FU and 62 without postoperative chemotherapy). Tumors were classified into the gastric- (G-), gastric and intestinal mixed- (GI-), intestinal- (I-), or unclassified- (UC-) phenotype according to the immunopositivity of HGM, MUC6, MUC2, and CD10 stainings. The associations among the gastric and intestinal phenotypic marker expression of the tumor, tumor TS expression, effect of postoperative chemotherapy with 5-FU, and the patient's prognosis were examined. Results. Of the 137 gastric carcinomas, 48 (35.0%), 58 (42.3%), 23 (16.8%), and 8 (5.8%)were classified as the G-, GI-, I- and UC-phenotype, respectively. The high TS expression of more than 25% tumor cell positivity was found in 25 (52.1%) of the 48 G-phenotype tumors, 39 (67.2%) of the 58 GI-phenotype tumors, 18 (78.3%) of the 23 I-phenotype tumors, and 4 (50.0%) of the 8 UC-phenotype tumors. The I-phenotype tumors were significantly correlated with the higher rate of the high TS expression as compared with the G-phenotype tumors (P<0.05). Among 48 patients with the G-phenotype tumor, the 5-year survival rate in patients with and without postoperative chemotherapy was 39.7 and 27.8%, respectively. The patients with postoperative chemotherapy had a significantly better prognosis than those without postoperative chemotherapy (P<0.05). Conversely, there were no significant correlations between the presence of postoperative chemotherapy and the patient's prognosis among patients with GI-, I-, and UC-phenotype tumors.Conclusions. These results indicate that postoperative chemotherapy with 5-FU could be effective for patients with the G-phenotype tumor, since the incidence of intratumoral expression of TS, the target enzyme of 5-FU, is significantly low in G-phenotype tumors.

症例は50歳,男性.腹痛にて近医受診. CTにて石灰化を伴った腹部腫瘤指摘.精査,加療目的に紹介される.小腸腫瘍疑いにて手術施行.回盲部より約20cmに結石を伴ったMeckel憩室を認めた.周囲が炎症性に癒着していたため憩室を含めて回盲部を切除した.憩室粘膜は異所性膵組織であった.結石は2.5×2.5×1.5cm, 1個認めた. Meckel憩室結石は極めて稀な疾患である.文献的考察を加え報告する.

We report a 43-year-old woman with advanced gastric cancer. Upper GI series and endoscopy revealed Type 3 gastric cancer and abdominal computed tomography showed marked para-aortic lymph node metastases suggesting curative resection was impossible. Neoadjuvant chemotherapy of cisplatinum, mitomycin C and etoposide markedly reduced the tumor, lymph nodes and para-aortic nodes. A total gastrectomy with D4 lymph node dissection, cholecystectomy and distal pancreaticosplenectomy was performed. The resected primary tumor had Grade 2 histology; some lymph nodes were Grade 3. Seven years after surgery the patient has no evidence of recurrence. In conclusion, D4 dissection after effective neoadjuvant chemotherapy may be useful in advanced gastric cancer with marked lymph node metastases.

当教室で1989年1月から1997年3月までの期間に内視鏡的粘膜切除(EMR)を施行し,切除後の潰瘍辺縁の生検で癌遺残陽性と診断されたが,諸々の事情により追加胃切除を行わなかった10例の経過について検討した.追加EMRを行わなかった3例でも,内視鏡的局所療法により1～30カ月後の生検では癌の遺残はなくなり,以後21～29カ月経過観察され陰性である. EMRを追加し,さらに必要に応じて局所療法を併用した7例も, 0.25～39カ月の経過で,癌の遺残はなくなり,以後2～89カ月経過観察され陰性である.よって,われわれがEMRの適応としている胃粘膜内癌では, EMR後に癌の遺残が認められても,追加EMRを含めた局所療法を繰り返すことにより外科的な追加胃切除の必要性は無いと思われた.

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.

We performed two independent evaluations of in situ polymerase chain reaction (in situ PCR) and Epstein-Barr virus encoded small RNA in situ hybridization (EBER ISH) for detection of Epstein-Barr virus infection in gastric carcinoma. In situ PCR is a novel technique with a high sensitivity which is a powerful aid for morphological diagnosis. Paraffin sections of gastric carcinomas from 96 cases were analyzed. Twenty-two of 96 cases (23%) were positive by in situ PCR, and 14 cases (15%) were positive by EBER ISH. Therefore there were 8 cases of EBV-DNA-positive gastric carcinoma without expression of EBER. To determine the significance of the expression of EBER in EBV-infection positive gastric carcinoma, we performed a clinicopathological study. There were two pathologic features in the gastric carcinoma with EBER. There was a significantly higher incidence of undifferentiated type and advanced cancer in EBER-positive gastric carcinomas. Therefore the expression of EBER contributes to the clinical pathologic feature of Epstein-Barr virus-associated gastric carcinoma.

The aim of this study is to clarify the characteristics of resected gastric cancer and the problems of treatment in elderly people. Blood loss was the only factor which was significantly difference between with and without a complication. In curability, curative resection was better prognosis than noncurative resection. Even in the elderly patient, operative mortality rate was low, considering a safety operation. In far advanced cases, we should think much of quality of life (QOL) in order to avoid a complication.

We carried out an analysis of para-aortic lymph node dissection in stage IIIVa advanced gastric cancer to evaluate the extended surgery. The subjects were 32 patients undergoing para-aortic lymph node dissection (D4), and 77 patients undergoing Group 2 and 3 lymph node dissection (D2, 3) which were conducted at the department from 1988 to 1995. No patients with double cancer, liver metastasis, and peritoneal dissemination were involved in the subjects. In case of stage IIIIIb advanced gastric cancer, the 5-year survival rate of patients with D4 (79.5%) was significantly higher than that of patients with D2, 3 (p<0.05). But, as to the prognosis in cases of stage IVa gastric cancer, no statistical differences were found between D4 and D2, 3. Even in cases of stage IIIIIb advanced gastric cancer with n1, 2 involvement, the 5-year survival rate of patients with D4 was significantly higher than that of patients with D2, 3 (p<0.05). These results suggest that D4 dissection is indicated for stage IIIIIb advanced gastric cancer with n2 involvement.

An univariate and multivariate analysis of para-aortic lymph node dissection in stage II similar to III b gastric canncer was carried out to evaluate the extended surgery. The patients were 27 cases of para-aortic lymph node dissection (D4) and 100 cases of Group2 lymph node dissection (D2) which were resected from 1988 to 1995 in the 2nd department of surgery, Showa university. The multivariate analysis was done by Cox's proportional hazard model. In cases of stage II similar to III b gastric cancer, the survival rate of D4 dissection group was significantly higer than that of D2 dissection group. D4 lymph node dissection was selected by multivariate analysis as the significant and independent prognostic factors affecting stage II similar to III gastric cancer.