Tsukasa Tsunoda

Collective review of small carcinomas of the pancreas.

To determine problems involved in the treatment and diagnosis of pancreatic cancer, a collective study of small carcinoma of the pancreas (2 cm or less in diameter) was performed. One hundred six cases were collected and analyzed. The results were as follows: In small carcinoma of the pancreas, the resectability rate was 99.0% and the operative mortality rate was 4%. Only 44% of the patients belonged to Stage I, and 14% belonged to Stage III or IV. Lymph node involvement, capsular invasion, retroperitoneal invasion, and vascular invasion were found in 30, 20, 12, and 9% of the patients, respectively. The postoperative cumulative 5-year survival rate was 30.3%, and that of Stage I was 37.0%. A small-sized tumor of the pancreas is not always an early carcinoma, but a tumor in Stage I may be regarded as an early carcinoma. Percutaneous transhepatic cholangiography and endoscopic retrograde cholangiopancreatography were the main diagnostic indicators in cases with and without jaundice, respectively. There was no specific single serum test for detecting small pancreatic cancer.

VEGF, basic-FGF, and TGF-β in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation

OBJECTIVE:Inflammatory bowel disease (IBD), the precise etiology of which remains unknown, is comprised of two forms of chronic intestinal inflammation; ulcerative colitis (UC) and Crohns disease (CD). Recent evidence increasingly suggests that IBD is the result of dysfunctional immunoregulation manifested by inappropriate production of mucosal cytokines. An abnormal microcirculatory system has also been implicated in its pathogenesis. To elucidate the mechanism of ischemic change in IBD, we assessed serum concentration levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), and plasma level of endothelin-1 (ET-1). We also investigated the expression of VEGF, b-FGF, and transforming growth factor-β1,2,3 (TGF-β1,2,3) in tissue by immunostaining.METHODS:Blood samples were obtained from 11 patients with UC, 11 patients with CD, and 10 patients as controls. Paraffin-embedded samples were used for an immunohistochemical study.RESULTS:The concentration levels (in picograms per milliliter) were as follows: for ET-1, UC: 127 ± 47.0, CD: 167.3 ± 35.1, and controls (asthma: 38.5 ± 23.8, p < 0.01; diverticulitis: 40.5 ± 25.6, p < 0.01), for b-FGF, UC: 9.2 ± 1.9, CD: 9.1 ± 1.5, and controls (asthma: 5.0 ± 0, p < 0.01; diverticulitis: 5.0 ± 0, p < 0.01), for VEGF, UC: 659.8 ± 181.0, CD: 740.0 ± 182.3, and controls (asthma: 193.7 ± 58.7, p < 0.01; diverticulitis: 199.6 ± 59.7, p < 0.01). The levels of VEGF and b-FGF were significantly higher in active IBD than those in the controls. There was a significant positive correlation among the serum levels of VEGF and b-FGF and the plasma level of ET-1; that is, elevated VEGF, b-FGF, and ET-1 levels correlated well with each other. Immunohistochemical studies showed increased venula in the submucosa and lamina propria. Overexpression of VEGF and b-FGF in endothelial cells was revealed and TGF-β2 and TGF-β3 were found in inflammatory cells of active IBD, but no change was observed around the vessels in the controls.CONCLUSIONS:It is suggested that the reciprocal reaction of these cytokines may contribute to angiogenesis in IBD by inducing intestinal ischemia through vasoconstriction.

The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection

To investigate the prognostic factors of pancreatic cancer, a retrospective analysis of 193 patients who underwent curative resection was conducted. Of the 193 patients, 38 (20%) survived for more than 5 years, the 5-year survival rates for stages I, II, III, and IV disease being 41%, 17% 11%, and 6%, respectively. According to a multivariate analysis, lymph node metastasis, intrapancreatic perineural invasion, and portal vein invasion were significant prognostic factors. Subsequently, a subgroup analysis concerning nodal metastasis and intrapancreatic perineural invasion was performed in 126 patients with records of these histological findings. In the group of patients without nodal metastasis, the 5-year survival rate for those without perineural invasion was 75%, whereas that for those with perineural invasion was 29%, the difference in survival of these subgroups being significant (P<0.02). In the group of patients with nodal metastasis, the 5-year survival rate for those without perineural invasion was 17%, while that for those with perineural invasion was 10%. The most favorable 5-year survival of 89% was observed in the subgroup of patients with stage I disease without perineural invasion. Thus, pancreatic adenocarcinoma categorized by the combination of these independent types of biological behavior showed 5-year survival rates ranging from very high to low, indicating that these two factors play an important role in the prognosis of this disease.

XAGE-1 expression in non : Small cell lung cancer and antibody response in patients

Purpose:XAGE-1 was originally identified by the search for PAGE/GAGE-related genes using expressed sequence tag database and was shown to exhibit characteristics of cancer/testis-like antigens. Four transcript variants XAGE-1a, XAGE-1b, XAGE-1c, and XAGE-1d have been identified thus far. We recently identified XAGE-1b as a dominant antigen recognized by sera from lung adenocarcinoma patients. We here investigated the mRNA expression of four XAGE-1 variants and XAGE-1 protein expression in non–small cell lung cancer (NSCLC). Humoral immune response to XAGE-1b was also evaluated in patients. Experimental Design: Forty-nine NSCLC specimens were analyzed for the expression of four XAGE-1 transcript variants by conventional 30-cycle and real-time reverse transcription-PCR and XAGE-1 protein expression by immunohistochemistry. Sera from 74 patients were analyzed for XAGE-1b antibody production by ELISA and Western blot. Results:XAGE-1b and XAGE-1d mRNA were detected in 15 and 6 of 49 lung cancer specimens, respectively. No XAGE-1a or XAGE-1c mRNA expression was observed. XAGE-1b mRNA expression was observed in 14 of 31 (45%) adenocarcinoma and 1 of 18 (6%) lung cancer with other histologic types. Immunohistochemical analysis using a XAGE-1 monoclonal antibody showed that 14 of 15 XAGE-1b mRNA-positive and 3 of 34 XAGE-1b mRNA-negative specimens expressed XAGE-1 protein. Seropositivity was observed in 5 of 56 patients with adenocarcinoma, whereas none of 18 patients with other histologic types produced XAGE-1b antibody. Conclusion: XAGE-1b is highly and strongly expressed in lung adenocarcinoma and immunogenic in patients, suggesting that XAGE-1b is a promising antigen for immunotherapy against lung adenocarcinoma.

Inhibitory effects of β-carotene, palm carotene, and green tea polyphenols on pancreatic carcinogenesis initiated by N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters

The effects of alpha-carotene, beta-carotene, palm carotene, and green tea polyphenols (GTP) on the progression stage of pancreatic carcinogenesis after rapid production of ductal lesions were studied in Syrian hamsters. Dose threshold inhibitory effects were noted for beta-carotene, 25 ppm, and palm carotene, 40 ppm, which includes 24 ppm beta-carotene reducing the numbers of putative preneoplastic lesions of duct epithelial hyperplasia and atypical hyperplasia, as well as carcinoma in situ and invasive carcinomas. GTP at doses of 500 and 5000 ppm, but not 100 ppm, also significantly decreased the numbers of hyperplasia and total duct lesions. Combined administration of 40 ppm palm carotene, and 50 ppm GTP similarly inhibited the lesion development. Alpha-carotene, however, did not affect pancreatic carcinogenesis. The results suggest that chemopreventive effects are exerted by beta-carotene and GTP above critical doses and that combined administration of palm carotene and GTP might be a candidate chemoprevention strategy for pancreatic cancer in humans.

A granulomatous liver abscess which developed after a toothpick penetrated the gastrointestinal tract: Report of a case

Abstract.An unusual case of a toothpick perforating the stomach, then penetrating the liver, and thereafter forming a liver abscess is reported. A 48-year-old woman who had ingested a toothpick 1 month earlier was admitted to our hospital because of severe epigastralgia which had progressively worsened. A laparotomy was performed because a granulomatous abscess in the liver due to this ingested foreign body was suspected. We found a granulomatous abscess in the liver due to the penetration of the toothpick through the stomach. The toothpick had become completely embedded about 2 cm deep in the left lobe of the liver. When dissecting the tumor, a 5.5-cm toothpick was removed, and a partial lateral resection of the liver was performed. The histological diagnosis was a hepatic abscess with granulomatous change. This was a rare case of a migration of an ingested toothpick into the liver through the stomach.

Solid-pseudopapillary carcinoma of the pancreas

A case of solid‐pseudopapillary carcinoma (SPC) of the pancreas in a 34‐year‐old Japanese woman is presented. An abdominal ultrasonography revealed a mass, which measured 10 cm in diameter, in the body and tail of the pancreas. The tumor was resected and it was originally diagnosed as a non‐functioning islet cell tumor. One year and five months later, the patient was re‐admitted to hospital, and liver metastasis was confirmed by ultrasonography. The patient died 6 days after the second transcatheter arterial embolization (TAE) required for the metastasis. The autopsy showed small foci of liver metastasis. A retrospective examination of the tumor suggested the diagnosis of SPC because of its characteristic solid and pseudopapillary structures, immunohistochemical findings, and liver metastasis. This case suggests that capsular invasion, specifically found at the surgical margin of the peritoneal side, may be an important pathological finding that is suggestive of malignant potential in solid‐pseudopapillary tumor. If there is such a finding in a surgical specimen, an intensive follow up should be advised to the clinician.

CD8+, CD56+ (natural killer-like) T-cell lymphoma involving the small intestine with no evidence of enteropathy: clinicopathology and molecular study of five Japanese patients.

The present study reports five CD8+, CD56+ (natural killer (NK)‐like) T‐cell lymphomas involving the small intestine without evidence of enteropathy, from Japan. Three were intestinal T‐cell lymphoma. The site of origin of the other two was not definitive. Four of five patients underwent emergency operation because of intestinal perforation. The small intestines of these patients had multiple ulcerative lesions with or without demarcated tumors. Histologically, the lymphoma cells were monomorphic or slightly pleomorphic and displayed epitheliotropism of varying degrees. Lymphoma cells of all patients shared the common phenotype: CD3+, CD4−, CD5−, CD8+, CD56+, CD57−, T‐cell intracellular antigen‐1+, granzyme B+. In contrast to nasal/nasal type NK‐cell lymphomas, they had clonal rearrangement of T‐cell receptor(TCR) genes and were negative for EBV‐encoded RNA. Immunohistochemistry and genetics suggested that three cases were of αβT‐cell origin and two cases were of γδT‐cell origin. There was no evidence of enteropathy in any patient. The cases followed a clinically aggressive course with a frequent involvement of lung. According to the classification based on the recent genetic studies of European enteropathy‐type intestinal T‐cell lymphoma (ETL), the present cases could be classified as type 2 ETL.

Gastrocolic fistula originating from transverse colon cancer: report of a case and review of the Japanese literature.

A 72-year-old woman was admitted to our hospital complaining of loss of weight, general fatigue, and upper abdominal pain. Barium studies suggested that a fistula was present between the proximal transverse colon and the stomach which originated from a carcinoma of the colon. A plain computed tomography (CT) scan confirmed the presence of a gastrocolic fistula. A two-thirds distal gastrectomy and right hemicolectomy with a resection of a bulky tumor in the mesocolon were performed en bloc. Histological examination revealed a well-differentiated adenocarcinoma of the transverse colon which was involved with the wall of the stomach. We were able to obtain information on 14 previous cases of gastrocolic fistula originating from transverse colon cancer in the Japanese literature, including the present case. The most common symptom was abdominal pain (64%). A preoperative diagnosis of fistula was confirmed in 10 of the 11 cases examined by barium studies. A plain CT and a CT scan after the barium studies may also be helpful in detecting fistula formation. A fistula between the carcinoma of the middle or distal transverse colon and the stomach was found in 13 of 14 cases, but not in our case. Only one case lived longer than 9 years, even though a surgical resection was possible in 9 of 11 cases.

Primary hepatic carcinoid tumor.

Abstract: A primary hepatic carcinoid tumor arising in a 49-year-old woman is reported. The patient was admitted with multiple hepatic tumors and treated by a left lobectomy and cholecystectomy. Cut sections of the specimen revealed a solid and necrotic mass, measuring 10 × 12 × 13 cm, with multiple small satellite nodules. Histologically, the tumor cells had small oval-shaped nuclei and presented with a trabecular arrangement and rosette-like formation. Both Grimelius and Fontana-Mason stainings were positive. The tumor cells were positive for chromogranin A and negative for other antigens. Ultrastructural studies of the tumor cells revealed duct-like formation with microvilli and a cluster of dense small immature neurosecretory granules in the cytoplasm. These findings were consistent with those of carcinoid tumors. Postoperatively, the patient was treated with repeated transcatheter arterial chemoembolization for any remnant tumors. However, she died of the disease 5 years after the initial surgery. The autopsy findings suggested the primary site to be the liver.