Masami Niki

Impact of the expression of cyclin-dependent kinase inhibitor p27Kip1 and apoptosis in tumor cells on the overall survival of patients with non–Early stage gastric carcinoma

The expression of p27Kip1 and apoptosis have been implicated in tumor aggressiveness and proved to be prognostic predictors for several human malignancies. In this study, the authors sought to investigate the expression of p27Kip1 and apoptosis and their potential significance in determining the prognosis of patients with non–early stage gastric carcinoma.

Clinical study to identify specific characteristics of cancer newly developed in the remnant stomach.

Abstract.Abstract.Background: Cancer newly developed in the remnant stomach (CRS) after partial gastrectomy is worthy of attention not only because it is a typical model of carcinogenesis but also from the aspect of cancer diagnosis.Methods: We treated 47 patients with CRS in the 20 years from 1979 to 1998. Clinicopathological variables, as well as long-term survival results after the second surgery, were reviewed to clarify whether there were any differences in the characteristics of this disease entity compared with the usual primary gastric cancer.Results: The mean time interval between the initial surgery and surgery for CRS was 25.8 years for patients with CRS with previous benign gastric lesions, and 10.6 years for those with previous gastric cancer. CRS was frequently detected at an early stage in the patients with previous cancer, and in the patients who had undergone reconstruction by the Billroth I method (regardless of the primary nature of the disease). Cancers with a differentiated histology developed more frequently in the patients who had undergone the initial surgery for cancer disease. Long-term survival results after the second surgery clearly demonstrated that surgical treatment for CRS was as effective as that for primary cancer in the upper stomach (PUC). In addition, it was confirmed that new lymphatic drainage into the lower mediastinum or the jejunal mesentery had developed after the initial gastric surgery.Conclusion: The findings suggested that patients with CRS and those with PUC should be treated similarly, although the findings of a high incidence of lymph node metastasis to the lower mediastinum and/or to the jejunal mesentery in the CRS patients should be taken into consideration.

Efficacy of intraperitoneal and intravenous chemotherapy and left upper abdominal evisceration for advanced gastric cancer

Background. The study was carried out to evaluate the efficacy of intraperitoneal (IP) and intravenous (IV) chemotherapy, as well as left upper abdominal evisceration (LUAE), for patients with advanced gastric cancer.Methods. We carried out a retrospective study of 348 patients who underwent gastrectomy for advanced gastric carcinoma between 1978 and 1998 at our institution and who had macroscopic type 3 or 4 cancer (Japanese classification) with depth of invasion to the serosal surface, but no liver metastasis or lymph node metastasis around the abdominal aorta. Cumulative survival rates were compared in patients who underwent gastrectomy together with: (1) intraoperative IP chemotherapy alone, (2) postoperative IV chemotherapy alone, (3) both IP and IV, or (4) no chemotherapy. Then patients were stratified according to the presence of peritoneal dissemination (P+) and its absence (P−). In P+ patients, survival was compared between those who received IV chemotherapy and those who did not, and between those who received IP chemotherapy and those who did not. Then, survival was compared between patients with high and low immunosuppressive acidic protein (IAP) levels. Finally, we compared cumulative survival rates in patients (stratified as P+ and P−) who underwent LUAE with cumulative survival rates in those who underwent total gastrectomy combined with resection of the pancreatic body, tail, and spleen (PS).Results. For P− patients, there was no survival advantage with adjuvant IP or IV therapy when compared with surgery alone. For P+ patients, however, there was an improvement in survival when patients received both IP and IV, compared with survival with surgery alone (P < 0.05). In P+ patients aged less than 60 years, there was improvement in survival for those who underwent IP therapy together with surgery (P < 0.05), but not for those who had IV chemotherapy after surgery. When LUAE was examined, there was a survival advantage for this procedure when there was no peritoneal dissemination. Four long-term survivors (surviving for more than 5 years) were identified in our study. Three of the 4 patients were aged less than 60 years, and all 4 had macroscopic type 4 gastric cancers.Conclusion. Although the prognosis for patients with invasive type gastric cancer remains poor, there have been a few long-term survivors, in whom this survival was associated with aggressive combination therapy, including surgery, IP, and IV therapy. P+ patients aged less than 60 years and patients with type 4 gastric cancer may stand to benefit most from such therapy. For P− patients, the role of adjuvant IP or IV therapy continues to be ambiguous, although LUAE in this population may be superior to PS.

Expression of transforming growth factor β (TGF-β) may contribute, in part, to the variations in histogenesis and the prevalence of peritoneal dissemination in human gastric carcinoma

Background. Alterations in the activity of transforming growth factor β (TGF-β) in humans have been implicated in fibrosis, immunosuppression, development of cancer, and other disorders. Scirrhous gastric carcinoma is characterized by cancer cells that infiltrate rapidly in the stroma with extensive growth of fibroblasts and fibrous tissue. Hence, the majority of studies examining the role of TGF-β in gastric carcinoma have focused on scirrhous carcinoma. Methods. We undertook a retrospective immunohistochemical study of gastric carcinoma in order to characterize TGF-β expression in malignant gastric lesions and to determine whether TGF-β expression was related to disease progression. Results. TGF-β expression in scirrhous gastric carcinomas was significantly higher than that in nonscirrhous gastric carcinomas. In patients with advanced gastric carcinoma with surgically curative resection, TGF-β expression was significantly higher in those patients who developed peritoneal recurrence after surgery than in those who did not develop such recurrence. Patients with TGF-β expression-positive tumors had significantly poorer survival than did those with TGF-β expression-negative tumors (P = 0.017). In addition, multivariate Cox proportional hazard model analysis showed that TGF-β immunohistochemical status was an independent prognostic factor (P = 0.0031). Conclusion. These data suggest that TGF-β may contribute, in part, to the variations in histogenesis and to the prevalence of peritoneal dissemination in gastric carcinoma.

Clinical problems in the surgical treatment of pancreaticobiliary maljunction

The results of surgical treatment of pancreaticobiliary maljunction at our department are described. The 67 patients who underwent surgery for this disease were divided by age into an adult group (45 patients, aged 16 years and over) and a pediatric group (22 patients, aged less than 16 years). The incidence of concomitant carcinoma before surgery and the incidence and severity of postoperative cholangitis were compared between these two groups. In addition, the cell proliferating activity of the biliary tract epithelium in cancer-free patients was compared between the two groups, using the proliferating cell nuclear antigen labeling index (PCNA LI). Ten patients (all adults) were diagnosed with cancer (gallbladder carcinoma in 7 and bile duct carcinoma in 3) before surgery. The surgical techniques used for reconstruction in the cancer-free patients were: in the adult group, hepaticoduodenostomy in 9 patients, Roux-en-Y hepaticojejunostomy in 17, jejunal interposition in 8, and another technique in 1. In the pediatric group, hepatico-duodenostomy was performed in 17 patients. Roux-en-Y hepaticojejunostomy in 3, and jejunal interposition in 2. Postoperative cholangitis occurred in 6 adults (including 2 with severe form) and 1 child (mild case). The PCNA LI of the biliary tract epithelium was high compared to control findings in the biliary tract epithelium of 10 adult patients without pancreaticobiliary maljunction. In the adult group with dilated extrahepatic bile ducts (n=10 examined) this index was 11.4% for the bile duct epithelium (control, 1.5%) and 12.7% for the gallbladder epithelium (control, 1.4%). In the adult group with non-dilated extrahepatic bile ducts (n=5 examined) it was 5.9% for the bile duct epithelium and 13.1% for the gallbladder epithelium. In the pediatric group (n=10 with extrahepatic bile duct dilatation) it was 7.5% for the bile duct and 9.7% for the gallbladder epithelium. (Differences from control values were all significant.) These results suggest that surgery for this disease should be performed as early as possible and that extrahepatic bile duct excision and biliary reconstruction should be performed whether or not extrahepatic bile ducts are dilated.

Diagnosis and Surgical Indications for Polypoid Lesions of the Gallbladder

To clarify the surgical indications for polypoid lesions of the gallbladder (PLG), we studied 62 patients who underwent cholecystectomy with the preoperative diagnosis of PLG. This included cholestero

Clinical Characteristics and Immunohistochemical Examination of Gastric Adenosquamous Carcinoma. Expression of Proliferating Cell Nuclear Antigen(PCNA), Apoptotic Cell, p53, CD44 and Intratumoral Microvessel Density(CD34).

胃腺扁平上皮癌 (以下, 本症) の特徴を検索する目的で, 本症を対象として一般型進行胃癌症例 (以下, 一般型) と比較検討した. まず両者を臨床的に比較し, PCNA, Apoptotic cell, p53, CD44, CD34の発現状態を免疫組織化学的に検討した. 臨床的に本症では肝転移率が高く, Stageの高い症例の多いことが特徴であり, その予後は一般型に比べて有意に不良であった. 本症のPCNA陽性細胞率は一般型に比べて有意に高値であり, Apoptotic Indexは一般型より有意に低率であった. p53, CD44発現陽性率は本症ではいずれも一般型に比べて有意に高率であり, 発現陽性例では両癌成分ともに同等に発現していた. さらに, 腫瘍内血管密度の検索では, 本症は一般型に比べて有意に高値であった. 今回の検討から, 本症は増殖活性が高く, p53などの遺伝子異常が蓄積され, アポトーシス活性が低く, 進展過程で豊富な新生血管が生じて癌細胞が転移しやすい状況を形成している可能性が示唆された.

Lymph Node Metastasis in Cancer of the Pancreatic Head Region and Indications for Pylorus-Preserving Pancreatoduodenectomy.

膵頭部領域癌のリンパ節転移状況と労胃壁リンパ節転移症例につき検索し, 全胃幽門輪温存膵頭十二指腸切除 (以下, PpPD) の適応を検討した. 過去16年間でD2以上のリンパ節郭清を施行し術後病理組織検査が十分になされた膵頭部領域癌56例を対象とした. リンパ節転移が高率であったのは, 膵頭部癌では浸潤型・十二指腸浸潤例, 乳頭部癌では潰瘍腫瘤型. 膵浸潤例, 下部胆管癌では浸潤型・膵浸潤例であった. 組織型では, 中・低分化型例のリンパ節転移率が高率であった. 労胃壁リンパ節転移は膵癌3例, 下部胆管癌1例で, 乳頭部癌には認めなかった. 膵癌の3例はすべて浸潤型で十二指腸第2部への浸潤陽性例であった. 下部胆管癌の1例は膵浸潤のある結節浸潤型で低分化型であった. また, 十二指腸第1部および胃への癌の直接浸潤は認めなかった. 以上より, 膵頭部領域癌に対するPpPDの適応は, 十二指腸浸潤のない膵頭部癌, 乳頭部癌, 膵浸潤のない下部胆管癌と考えられた.