Trefoil factor 1 inhibits the development of esophageal adenocarcinoma from Barrett's epithelium.

Trefoil factor family 1 (TFF1) is one of three members of the trefoil factor family that are abundantly expressed in the gastrointestinal mucosal epithelium. Recent studies have shown that TFF1 acts as a tumor suppressor in gastric, pancreatic and hepatocellular carcinogenesis; however, little is known about its function in esophageal carcinogenesis, especially in esophageal adenocarcinoma (EAC). Barrett's epithelium is the metaplastic columnar epithelium of the esophagus and a known premalignant lesion of EAC. To investigate the role of TFF1 in EAC development, a mouse model of Barrett's epithelium was employed, and human specimens of EAC were assessed by immunohistochemistry (IHC) and methylation-specific PCR. Wild-type (WT) mice underwent gastrojejunostomy on the forestomach, resulting in the development of Barrett's epithelium-like (BE-like) epithelium adjacent to the anastomotic site. BE-like epithelium in these mice expressed TFF1, indicating the association of TFF1 with esophageal adenocarcinoma. TFF1-knockout (TFF1KO) mice underwent the same procedure as well, revealing that a deficiency in TFF1 resulted in the development of adenocarcinoma in the anastomotic site, presumably from BE-like epithelium. IHC of human samples revealed strong TFF1 expression in Barrett's epithelium, which was lost in some EACs, confirming the association between TFF1 and EAC development. Aberrant DNA hypermethylation in TFF1 promoter lesions was detected in TFF1-negative human EAC samples, further confirming not only the role of TFF1 in EAC but also the underlying mechanisms of TFF1 regulation. In addition, IHC revealed the nuclear translocation of ß-catenin in human and mouse EAC, suggesting that activation of the Wnt/ß-catenin pathway was induced by the loss of TFF1. In conclusion, these results indicate that TFF1 functions as a tumor suppressor to inhibit the development of esophageal carcinogenesis from Barrett's epithelium.

Trefoil factor family 2 inhibits cholangiocarcinogenesis by regulating the PTEN pathway in mice.

Trefoil factor family 2 (TFF2) is one of three trefoil factor family proteins and is expressed abundantly in the gastrointestinal epithelium. Recent studies have shown that TFF2 acts as a tumor suppressor in gastric and pancreatic carcinogenesis; however, little is known about its function in cholangiocarcinogenesis. To investigate the function of TFF2 in cholangiocellular carcinoma (CCC), immunohistochemistry of surgically resected human CCC samples was performed. TFF2 expression was upregulated in the early stage and lost in the late stage of cholangiocarcinogenesis, suggesting the association of TFF2 and CCC. A TFF2 expression vector was then transfected into a CCC cell line (HuCCT1) in vitro, revealing that TFF2 functions as a tumor suppressor not only by inhibiting proliferation and invasion but also by promoting the apoptosis of cancer cells. In addition, PTEN signaling activity was downregulated by TFF2, suggesting an association between TFF2 and PTEN. Next, hepatic carcinogenesis model mice (KC; albumin-Cre/Lox-Stop-Lox KRASG12D) were bred with TFF2-knockout mice to generate a TFF2-deficient mouse model (KC/TFF2-/-). Although the incidence of hepatocellular carcinoma was not different between KC/TFF2-/- mice and control mice, biliary intraepithelial neoplasm (BilIN), the precursor of CCC, was frequently found in the biliary epithelium of KC/TFF2-/- mice. Immunohistochemistry revealed that BilIN samples from these mice did not express PTEN. In addition, two KC/TFF2-/- mice developed CCC adjacent to BilIN, suggesting that TFF2 functions to inhibit the development of CCC in vivo. These results indicate that TFF2 acts as a tumor suppressor to inhibit the development of CCC by regulating PTEN activity.

[Clinical analysis of bladder cancer].

PURPOSE: We report our clinical experiences of treatment for bladder cancer. MATERIAL AND METHODS: Clinical analysis was performed about 282 primary bladder cancer patients who performed first time treatment in our hospital from January 1991 to December 2002. RESULTS: As to T classification, 127 patients were in Ta, 89 in T1, 27 in T2,18 in T3, eight in T4 and 13 in Tis, respectively and among those, there were seven patients with a metastasis. Most patients of superficial cancer were treated by combined use of TUR and instillation therapy. There were few patients of total cystectomy performed as a first time treatment in the case of invasive cancer in our clinic and comparatively many preservation therapies by TUR, systemic chemotherapy and radiotherapy combined use were performed. Cancer recurred to 90 cases in 275 patients, and 18 patients died owing to cancer progression. Five and ten-years-recurrence free rate in the whole were 59.5 and 44.3%, five and ten-years-disease specific survival rate were 92.9 and 85.9%. Furthermore, 5-years-disease specific survival rate classified by T stage were 100, 100, 71.2, 46.7 (3-years-survival), 53.6, 83.3% in Ta, T1, T2, T3, T4, Tis, respectively and the significant difference was observed. The disease specific five-years survival rate of the whole local invasive carcinoma (T2-4N0M0) was 57.5% and 70.2% in the case of preservation therapy performed by TUR, chemotherapy and radiotherapy combined use. CONCLUSIONS: An appropriate treatment according to the each case is needed for bladder cancer.

[Examination of the anesthesia on transperineal prostate biopsy--saddle block versus caudal block].

We examined the anesthesia of transperineal prostate biopsy under saddle block or caudal block. Between July 2003 and September 2004, we performed transperineal prostate biopsy under saddle block and caudal block, in 59 and 78 patients, respectively. We evaluated the pain score with the FACES Pain Rating Scale (0-5) and examined side effects on each anesthesia. There was no significant difference in the pain score of anesthesia prick between saddle block and caudal block (1.51 +/- 1.03 versus 1.39 +/- 0.98 respectively, P = 0.629), but the biopsy prick under saddle block revealed significantly (P < 0.0001) lower pain score (0.05 +/- 0.22) than caudal block (1.18 +/- 1.22). Saddle block caused post-operative retention more frequently than caudal block and required the patient to rest in bed for several hours after prostate biopsy. Saddle block was useful for relieving the pain of biopsy. In future, we need to consider using a method with fewer side effects.

[Simultaneous bilateral testicular tumors with different cell types: a case report].

A 22-year-old man presented to our out-patient clinic with the chief complaint of a painless mass in the right scrotum and lymph node swelling around the abdominal aorta in October, 2002. The bilateral testicular tumors were palpated and visualized by ultrasound and magnetic resonance imaging (right phi5 cm, left phi2 cm in diameter). Computed tomography revealed a metastatic lymph node around the abdominal aorta (3 x 3 x 10 cm in size). He underwent bilateral radical orchiectomy after frozen storage. Enucleation of the left testicular tumor was not performed because of its irregular demarcation. Histological examination revealed typical seminoma of the right testis and embryonal carcinoma of the left testis. Retroperitoneal lymph node dissection was performed after 4 courses of systematic chemotherapy (bleomycin, etoposide, platinum). No viable tumor cells were present histologically in the excised lymph nodes. The postoperative course was good and uneventful at 16 months under androgen replacement therapy without disease recurrence.

[Inverted papilloma of urinary bladder in two patients with urination difficulty as initial symptom].

We report two men with inverted papilloma of urinary bladder with urination difficulty as initial symptom. One was 51 years old and the other was 60 years old. Ultrasound revealed a tumor in the bladder and cystoscopy revealed a smooth-surfaced tumor with a stalk at the bladder trigon. They underwent transurethral resection of the bladder tumor and histopathological findings were consistent with inverted papilloma. Postoperatively, they are free of urination difficulty and have had no recurrence for 3 and 1 years, respectively.

[Two cases of female paraurethral leiomyoma].

We report two cases of female paraurethral leiomyoma. Two Japanese women (51 and 44 years old) were referred to our department with the complaint of a painless mass at the external genitalia. Both tumors were resected transvaginally and histopathologicaly diagnosed as leiomyoma without any evidence of infiltration into the surrounding tissue. One hundred and twenty-eight cases of female paraurethral leiomyoma are collected from the Japanese literature and are discussed.

[Gastrointestinal stromal tumor of the stomach mimicking adrenal tumor: a case report].

A gastrointestinal stromal tumor of the stomach mimicking an adrenal tumor in a 67-year-old woman is reported. The patient sought medical attention for left flank pain in December 2001. A spherical calcification was evident in the left hypochondrium in an abdominal radiography, and computed tomography revealed a mass 8 cm in diameter at the upper pole of the left kidney. She then was admitted to our hospital. Physical examination and laboratory screening showed hypertension, diabetes mellitus and slight hemoconcentration. Endocrine examination showed normal serum adrenal hormone concentrations. Magnetic resonance imaging again demonstrated the mass, which showed enhancement along its margins after intravenous contrast administration. With a preoperative diagnosis of adrenal tumor, we performed total resection. The pediculated tumor, arising from the stomach, showed c-kit immunohistochemical staining permitting a histopathological diagnosis of gastrointestinal stromal tumor.