Adrenomedullin, Bcl-2 and microvessel density in normal, hyperplastic and neoplastic endometrium.

Adrenomedullin (ADM) is a multifunctional 52-amino acid peptide involved in numerous physiological and pathological processes, including angiogenesis, growth regulation, differentiation, and vasodilation. ADM is thought to act through the G protein-coupled receptor calcitonin receptor-like receptor, with specificity being conferred by receptor-associated modifying protein 2. The aim of the present study was to clarify the roles of ADM status, and tumor vessels in endometrium. Specimens were examined for ADM, microvessel density (MVD), area of venules (AV) and Bcl-2 oncoprotein using an immunoperoxidase method. The difference of ADM between normal proliferative phase and hyperplasia without atypia was significant (P < 0.05). The level of Bcl-2 was significantly different between hyperplasia without atypia and hyperplasia with atypia (P < 0.05). ADM, MVD and AV in the endometrium increased in a stepwise manner from normal, simple or complex hyperplasia with or without atypia to grade 1 adenocarcinoma. In contrast, expression of Bcl-2 oncoprotein was decreased. These parameters identify the role of ADM expression and Bcl-2 protein in relation to cell growth and vasodilating in the neoplastic changes.

[A case report of autoimmune pancreatitis with Mikulicz' s disease and diabetes mellitus].

A 56-year-old man with bilateral swelling of lacrimal glands was admitted to our hospital. He was diagnosed as autoimmune pancreatitis with Mikulicz' s disease presenting the swelling of lacrimal glands, submandibular glands and the pancreas head and tail. Treatment with systemic prednisolone resulted in improvement of the swelling of these glands and pancreas. On the immunohistochemical examination, infiltration of CD4- and CD8-positive T lymphocytes was detected in the lacrimal gland, the submandibular gland, the gall bladder and the pancreas. Infiltration of IgG4-positive plasma cells was detected in the submandibular gland, the gall bladder and the pancreas. These results may suggest the presence of common etiology between autoimmune pancreatitis and Mikulicz' s disease.

Increased expression of thymidine phosphorylase in tumor tissue in proportion to TP-expression in primary normal tissue.

Thymidine phosphorylase (TP) is considered to be a key enzyme affecting the prognosis of patients with advanced gastrointestinal cancer. We tried to demonstrate the correlation of TP expression in tumor tissue and adjacent normal tissue, that is, primary normal tissue. The present study was designed to quantify TP level by enzyme-linked immunosorbent assay (ELISA) in tumor tissue and adjacent normal tissue obtained from 42 hepato-gastrointestinal cancer patients including 15 with gastric, 19 with colorectal and 8 with hepatocellular carcinomas. TP levels in tumor tissues were higher than those in adjacent normal tissues (p<0.001). There was a significant correlation between the expression of TP in tumor tissue and adjacent normal tissue (R=0.711, p<0.001; y=23.420+1.534x). On the other hand, there was no significant correlation between the ratio of tumor to adjacent normal tissue levels of TP (TP T/N) and expression of TP in tumor tissue (R=0.250, p=0.110). Thus, TP expression in tumor tissue may be high in proportion to TP expression in primary tissue. Furthermore, in clinical care, not only TP level in tumor tissue but also TP T/N value should be considered when using anticancer agents that become effective after conversion by TP to the active drug 5-FU.

Chemotherapy and serum hyaluronic acid levels in malignant peritoneal mesothelioma.

We report a case of malignant peritoneal mesothelioma in a 63-year-old man. Right hemicolectomy, partial ileectomy, partial omentectomy, excision of the abdominal wall, and catheterization for intraperitoneal infusion chemotherapy were performed as surgery. Histopathologically, the tumor was composed of papillary and sheet-like proliferation of atypical cells for which an Alcian Blue digestive test with hyaluronidase was positive. By immunohistochemical staining, the tumor cells were stained against HBME-1 and thrombomodulin antibodies. The final diagnosis was a diffuse malignant mesothelioma of the epithelial type. Sequential adjuvant chemotherapies of cisplatin (ip) plus 5-fluorouracil (iv), cisplatin (iv) plus 5-fluorouracil (iv), and mitomycin C (iv) were administered. He is still alive 46 months after surgery. Moreover, the increase in serum hyaluronic acid levels has been related to tumor volume, and has been useful for clinical follow-up. Secondly, we reviewed major chemotherapy previously described for malignant mesothelioma. The total response rate was 469 of 2,493 cases (18.8%). The response rates with single agent chemotherapy, combination chemotherapy, intraperitoneal or intracavitary chemotherapy, continuous hyperthermic peritoneal perfusion chemotherapy, and immunochemotherapy were 150 of 1,146 cases (13.1%), 209 of 1,019 cases (20.5%), 63 of 133 cases (47.4%), 11 of 13 cases (84.6%), and 36 of 182 cases (19.8%), respectively. Direct exposure of antitumor agent to the peritoneal surface is considered to be most effective against malignant peritoneal mesothelioma.

Surgical treatment for an extrahepatic portosystemic shunt: a case report.

An extrahepatic portosystemic shunt that has neither liver cirrhosis nor portal hypertension is rare. A 60-year-old Japanese woman who had been suffering chronic liver disease and anemia with mild disorientation was admitted to investigate general fatigue with dizziness and disorientation. The laboratory data revealed mild pancytopenia and liver dysfunction including hyperammoniemia, an increased Indocyanine Green 15-min retention rate, and a decreased Fischer's ratio. Color Doppler ultrasonography, computed tomography, and arterial portography revealed an extrahepatic portosystemic shunt that extended tortuously from the superior mesenteric vein into the inferior vena cava, and decreased blood flow in the main portal vein. Judging from intraoperative measurement of portal pressure and intraoperative portography, shunt ligations were performed at both the efferent portion of shunt from the superior mesenteric vein and the afferent portion of the shunt into the inferior vena cava, and resection of the spleen was also performed. On the postoperative laboratory data, pancytopenia disappeared, and liver function improved. Postoperative abdominal imaging showed increased blood flow in the main portal vein and disappearance of the shunt vessel. Moreover, symptoms present before surgery also disappeared. In conclusion, surgical treatment of extrahepatic portosystemic shunts may result in better postoperative quality of life if it is performed in carefully selected patients.

Thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in hepatocellular carcinoma and metastatic liver cancer.

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are considered to be key enzymes affecting the prognosis for patients with various cancers. We tried to prove the correlation of TP and DPD expression in hepatocellular carcinoma (HCC) and liver metastasis. We quantified TP and DPD levels by an enzyme-linked immunosorbent assay (ELISA) in the tumor (T) and adjacent normal tissue (N) obtained from 8 HCC patients, and 11 liver metastasis patients together with 9 of their primary cancers. TP levels were higher in the primary cancer, liver metastasis, and HCC compared with each adjacent tissue. TP levels were higher in HCC than in liver metastasis, and TP levels in the adjacent tissues of HCC were also higher than those in adjacent tissues of liver metastasis. TP levels were higher in liver metastasis than in primary cancer, and TP levels in adjacent tissues of liver metastasis were also higher than those in adjacent tissues of primary cancer. However, there were no differences in TP T/N ratio between HCC and liver metastasis, and between primary cancer and liver metastasis. DPD levels were lower in the liver metastasis compared with the adjacent liver tissues, and DPD levels in liver metastasis or its adjacent liver tissues were higher than those in primary cancer or its adjacent tissues. There were no differences in DPD T/N ratio between HCC and liver metastasis, and between primary cancer and liver metastasis. Thus, we demonstrated that TP was highly expressed in liver malignancy. We may be able to increase the success of anticancer chemotherapy for liver malignancy while decreasing the side effects by analysis of T/N ratios in TP, DPD, and TP/DPD in addition to TP expression.

Preoperative endoscopic analysis of thymidine phosphorylase and dihydropyrimidine dehydrogenase in gastrointestinal cancer.

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are considered to be key enzymes affecting the prognosis for patients with advanced gastrointestinal cancer. Preoperative examination of TP and DPD expression levels and assessment of these enzymes in inoperable cancer patients may contribute to successful treatment. We tried to prove the correlation of TP and DPD expression in preoperative specimens by endoscopy and in surgical specimens. The present study was designed to quantify TP and DPD levels by enzyme-linked immunosorbent assay (ELISA) in tumor tissue obtained from 30 gastrointestinal cancer patients by preoperative endoscopy and surgery, including 15 gastric and 15 colorectal cancers. Successful cases as those in which cancer cells were demonstrated histologically in preoperative specimens by endoscopy were 12 (success rate: 80%) in gastric cancer patients, and 15 (success rate: 100%) in colorectal cancer patients. In successful cases, there were almost significant correlations in all cases, gastric cancer, and colorectal cancer among the expression of TP, DPD, and TP/DPD ratio in each preoperative specimen by endoscopy and surgical specimen, respectively. On the other hand, in the gastric cancer group, 3 unsuccessful cases resulted in a significant departure from ideal equation compared with 12 successful cases. In actual clinical care, physicians should pay attention to and evaluate carefully the data from endoscopical biopsy specimens in which cancer cells may not be demonstrated histologically. Thus, endoscopic analysis of TP and DPD expression in preoperative or inoperable cancer patients may contribute to successful treatment.

Comparative analysis of thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in gastric and colorectal cancers.

Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are considered to be key enzymes affecting the prognosis for patients with gastric and colorectal cancers. We tried to prove the correlation of TP and DPD expressions in gastric and colorectal cancers. The present study was designed to quantify TP and DPD levels by an enzyme-linked immunosorbent assay (ELISA) in tumors and normal tissues obtained from 16 gastric and 20 colorectal cancer patients. TP and TP/DPD ratio in the tumor specimens were almost all higher than those in each normal tissue, especially for tumors in the progressive state. In the early stage of the colorectal cancer group, DPD in the normal tissues were higher than those in the tumor specimens. There were no significant differences between TP levels in the tumor specimens of the two groups, whereas in stages III and IV, those of the gastric cancer group tended to be higher than those of colorectal cancer group. In stages I and II, DPD levels in the tumor specimens tended to be higher in the gastric cancer group than in the colorectal cancer group. DPD T/N was higher in the gastric cancer group than in the colorectal cancer group. There were no significant differences between TP/DPD ratios in the tumor specimens of the two groups, whereas those in normal tissue were higher in the gastric cancer group than in the colorectal cancer group. We may be able to achieve the successful effects or reduction of side effects of anticancer chemotherapy for gastric and colorectal cancer using the results of this study.

A traumatic neuroma of the bile duct: a case report.

Traumatic neuroma of the bile duct is not a true neoplasm, but a reactive proliferation of pericholangial nerve tissue induced by injury. A 60-year-old Japanese man was admitted to investigate obstructive jaundice. He had undergone cholecystectomy and common bile duct exploration 17 years previously. Ultrasonography and computed tomography showed a pneumobilia with dilatation of the intrahepatic biliary ducts. Endoscopic retrograde cholangiography and spiral-computed tomography cholangiography revealed biliary stenosis in the hepatic hilus with dilatation of the intrahepatic biliary ducts. Celiac angiography and arterial portography showed neither tumor stains nor signs of vessel invasion. At surgery, the confluent portion of the intrahepatic biliary ducts in the hepatic hilus was hardly palpable and deformed, but frozen-section microscopic examination confirmed that no malignant cells were present. Anastomosis of the right and left extrahepatic bile duct to the jejunum, reconstructed by Roux-en-Y hepaticojejunostomy, was performed. Histological examination revealed a nodule composed of a haphazard proliferation of nerve fascicles in the fibromuscular layer of the bile duct which were positively stained for S-100 protein. The pathological diagnosis was traumatic neuroma of the bile duct. Thus, the possibility of traumatic neuroma should be considered in the differential diagnosis of patients with late-onset jaundice after biliary tract surgery.