Junji Tsuruta

Differential distribution of basement membrane type IV collagen α1 (IV), α2 (IV), α5 (IV) and α6 (IV) chains in colorectal epithelial tumors

In this study, we examined the relationship between the histopathological grade and immunohistochemical localization of six genetically distinct type IV collagen α chains, the major component of basement membrane (BM), in normal and neoplastic colorectal tissues. In the normal colorectal mucosa, α1/α2(IV) and α5/α6(IV) chains were stained in all epithelial BM. However, α3/α4(IV) chains were restrictively immunostained in the BM of the apical surface epithelium. Similar immunostaining profiles for α1/α2(IV) and α5/α6(IV) chains were observed in tubular adenomas with mild/moderate atypia. However, in intramucosal carcinomas, both α1/α2(IV) chains were linearly stained in the BM of cancer cell nests, while the assembly of α5/α6(IV) chains into the BM was inhibited in a discontinuous or negatively stained pattern. The normal colorectal mucosa forms a second network of BM composed of α5/α6(IV), partly α3/α4(IV) chains, in addition to the classic network of α1/α2(IV) chains. The differential immunohistochemical localization of the type IV collagen α5/α6 chains could be one diagnostic marker for the invasiveness of colorectal cancer.

Intraductal papillary tumors of the pancreas. Histopathologic correlation of MR cholangiopancreatography findings.

Purpose: To evaluate MR cholangiopancreatography (MRCP) findings of intraductal papillary tumors of the pancreas and correlate them with histopathology. Material and Methods: Seventeen patients with intraductal papillary tumor of the pancreas underwent MRCP before surgery. MRCP findings were correlated to histopathology with regard to the presence of septa and excrescent nodules in the cystic lesion, communication between the cystic lesion and the main pancreatic duct (MPD), degree of dilatation of MPD, and dilatation of the common bile duct (CBD). Results: MRCP demonstrated septa in 17 cases (100%), excrescent nodules in 8 cases (47.1%), communication between the intraductal papillary tumor and the MPD in 14 cases (82.3%), dilatation of MPD over 50% in 6 cases (35.3%), and dilatation of CBD in 3 cases (17.6%). These findings showed excellent correlation with histopathology. The septum on MRCP corresponded with a layer of connective tissue with pancreatic duct epithelium. Excrescent nodules in the carcinomas consisted not only of malignant cells, but also of dysplasia and adenoma. Excrescent nodules in adenomas were consistent not only with minimal papillary growth of adenoma, but also with proliferation of fibrosis, and hematoma and organized fibrin with minimal fibrosis. Pancreatic tissue was affected by chronic pancreatitis in all cases. Cases with dilatation of CBD on MRCP were due to microscopic invasion by the carcinoma. Conclusion: MRCP appearances of intraductal papillary tumors are well correlated with the findings at histopathology.

Direct evidence for systemic fibrinogenolysis in a patient with metastatic prostatic cancer

Although the possible occurrence of systemic fibrinogenolysis has been suggested in patients with metastasising prostatic cancer (MPC), direct evidence is lacking. We report on a patient with MPC whose laboratory data were consistent with hyperfibrinolysis: marked decrease of alpha 2-antiplasmin (AP) level (less than 50% of normal), increase of plasmin-alpha 2-antiplasmin complex, D-fragment of fibrin and fibrinogen degradation products [FDP(D)] and cross-linked fibrin degradation products (XDP). The patient neither showed laboratory nor clinical evidence for consumption coagulopathy except for a slight increase in thrombin-antithrombin III complex level. Immunoblotting of the patients serum using an anti-fibrinogen antibody revealed the presence of a 250 kDa protein in addition to DD fragments. Following reduction of this protein by 2-mercaptoethanol after extraction from SDS-PAGE gel, gamma-chain of fibrinogen (47 kDa) was found by immunoblotting using a monoclonal antibody recognising a 86-302 residue of the gamma-remnant of fibrinogen. Moreover, the 250 kDa protein did not bind to Sepharose 4B to which a monoclonal antibody recognising the N-terminus of fragment D was conjugated. These findings indicated that this protein was not fragment DY, but rather fibrinogen fragment X. With the retraction of the prostatic tumour by an effective therapy, the patients AP level increased gradually. When the plasma AP level rose to 60% of normal, the fragment X was no longer detectable. These findings suggested that systemic fibrinogenolysis occurred in the patient with MPC only when AP levels were markedly decreased.

Lingual carcinoma : correlation of MR imaging with histopathological findings

Purpose: To determine the utility of MR imaging in the evaluation of lingual carcinomas. Material and Methods: Eleven patients with lingual carcinoma were evaluated with MR imaging including dynamic study within one week before surgery. Nine patients underwent preoperative chemotherapy or irradiation, and 2 patients had no preoperative treatment. Delineation of the tumor, the contrast between tumor and surrounding tissue, and extent of the tumor were evaluated in a blinded manner. After glossectomy, MR images were correlated with pathological findings. Statistical analysis was performed on the visual assessment ratings. Results: Blinded evaluation suggested that dynamic and T2-weighted images (T2WI) were significantly superior to postcontrast T1WI in demonstrating the lesion. There were no significant differences between dynamic MR images and T2WIs. However, histopathological correlation showed that in patients with preoperative treatment, dynamic MR imaging demonstrated more accurately the size and extent of the residual tumor than did T2WI and postcontrast T1WI, which tended to demonstrate an area of signal abnormality that was more extensive than the true size of the residual lesion. In patients without preoperative treatment, dynamic MR imaging, T2WI, and postcontrast T1WI gave an equivalent depiction of the extent of the carcinoma. Conclusion: In patients with no preoperative treatment, dynamic MR imaging does not appear to offer any advantage over T2WI. However, in patients with preoperative treatment, dynamic MR imaging provides a more accurate assessment of the residual tumor than do T2WI and postcontrast T1WI.

Acute suppurative thyroiditis in an asymptomatic woman: an atypical presentation simulating thyroid carcinoma

Patients with acute suppurative thyroiditis usually have pain or tenderness in the anterior part of the neck associated with erythema and dysphagia. A 26‐year‐old Japanese woman with none of these symptoms presented with a left anterior cervical mass. Since physical examination and laboratory studies showed a firm and irregular tumour located in the left lobe of the thyroid without any inflammatory signs, we made a diagnosis of thyroid carcinoma. After surgery, histological examination of the thyroid specimen revealed various changes of severe inflammation, and a barium swallow demonstrated a left pyriform sinus fistula. We describe here a unique case of acute suppurative thyroiditis in an asymptomatic woman.

Expression of brain-type glycogen phosphorylase is a potentially novel early biomarker in the carcinogenesis of human colorectal carcinomas

OBJECTIVE:Our previous studies have demonstrated the significant role of brain-type glycogen phosphorylase (BGP) in the carcinogenesis of gastric carcinoma. The aims of the present study were to investigate the expression of BGP in colorectal carcinoma as well as the timing of this expression in the adenoma-carcinoma sequence (ACS), in comparison with the overexpression of p53 protein. We also sought to identify this marker in the particular colorectal mucosa bearing de novo carcinoma.METHODS:The expression of BGP and p53 protein in colorectal carcinoma using affinity purified specific anti-human BGP antibody (Ab) and anti-p53 Ab was studied using 96 resected specimens. Further investigation to examine the timing of BGP expression in comparison with p53 overexpression was carried out using 13, 18, eight, and 16 specimens of adenoma with mild, moderate, and severe dysplasia, and carcinoma in adenoma, respectively. The BGP immunohistochemistry in whole resected human colorectal mucosa (two with carcinoma and one with ulcer) was carried out using specific anti-BGP and anti-p53 Ab.RESULTS:The BGP visualized by immunohistochemistry was commonly present in colorectal carcinoma (83.3%). The expression of this molecule during ACS showed excellent correlation with the increased dysplasia and was found before p53 overexpression, whereas no BGP expression was seen in the normal human large intestine remote from the cancer foci. Positive staining in overtly normal-looking colonic mucosa was observed mainly around carcinomas without any adenoma component.CONCLUSIONS:The present study is the first to localize the BGP molecule in colorectal carcinoma, adenoma, and normal mucosa. It is suggested that BGP is a novel biomarker for carcinogenesis in both the pathways of ACS and the de novo colorectal carcinoma.

Interstitial-tissue localization of high-molecular-weight kininogen in guinea-pig skin.

A rabbit antibody against the light-chain of guinea-pig high-molecular-weight (HMW) kininogen, which was specific to HWM kininogen and did not recognize low-molecular-weight kininogen, was prepared. This antibody demonstrated the presence of HMW kininogen antigen at the interstitial-tissue space in the guinea-pig skin by means of immunohistochemistry. The interstitial-tissue HMW kininogen antigen was extracted from the skin. This antigen molecule in the skin extract behaved identically as HWM kininogen of plasma in slab-polyacrylamide gel electrophoresis under the presence of sodium dodecyl sulfate followed by immunoblotting. Therefore, it was concluded that HMW kininogen was present in the interstitial-tissue fluid in the skin. The amount of HMW kininogen in the skin extract was quantified by a sandwich enzyme-linked immunosorbent assay with the anti-light-chain antibody and a goat anti-guinea-pig HMW kininogen antibody. On the assumption that the interstitial-tissue volume is 50 ml/100 g wet skin tissue, the average concentration of HMW kininogen in the interstitial-tissue fluid of the skin was calculated to be 23% of the plasma concentration. On the other hand, the proportion of intravascular HMW kininogen (derived from blood remaining in the vessels of the harvested skin) in relation to the total HMW kininogen in the skin extract was quantified by measuring the radio-labelled HMW kininogen which had been injected intravenously as a tracer of the intravascular HMW kininogen. About 5% of the total HMW kininogen in the skin extract was calculated to be derived from the intravascular blood volume of the skin, indicating that the majority of the HMW kininogen in the skin extract was derived from the extravascular-tissue space.

Blood Transfusion Induced Opportunistic Adult T Cell Leukaemia/Lymphoma after Hodgkin's Disease.

A patient previously treated for Hodgkins disease (HD) developed secondary adult T cell leukaemia/lymphoma (ATL) after blood transfusion. Immunohistochemical analysis and polymerase chain reaction support the diagnosis. To the best of our knowledge this is the first occurrence of transfusion induced ATL occurring as a second malignancy after treatment for HD. The leukaemia/lymphoma probably developed on the basis of underlying immunosuppression.

Nuclear Localization of Brain-type Glycogen Phosphorylase in Some Gastrointestinal Carcinoma

Our previous reports have demonstrated frequent and strong expression of glycogen phosphorylase (EC 2.4.1.1) activity mainly in the cytoplasm of gastric carcinoma. Although previous studies have suggested the phosphorylase glyco-syltransferase system to be in the nucleus from enzyme histochemical analyses, intranuclear localization of the phosphorylase has not been fully established. The aims of the present study are to investigate the nuclear localization of glycogen phosphorylase and to identify the isoform of phosphorylase in the nucleus of gastrointestinal carcinoma. The activity of glycogen phosphorylase in carcinoma cells corresponding to the nucleus was demonstrated using enzyme cytochemical analysis. The phosphorylase activity coincided with localization revealed by immunocytochemistry using affinity-purified specific anti-human brain-type glycogen phosphorylase antibody. The isoform expressed in the nuclei of carcinoma cells was identified as bei ng only the brain type according to a polymerase chain reaction-based assay using RNA obtained from gastric carcinoma cells and primers specific to muscle, liver and brain types of glycogen phosphorylase. The intranuclear localization of the brain-type isoform was confirmed by immunoelectron microscopical analyses. Further investigation to examine the nuclear localization in human carcinoma tissue (145 and 25 specimens with gastric and colonic carcinoma respectively) was carried out by immunohistochemistry using specific anti-brain-type antibody. Nuclear immunostaining was observed in seven cases out of 145 gastric carcinoma. The present study is the first to clarify the nuclear localization of glycogen phosphorylase with enzymatic activity in gastrointestinal carcinoma. The isoform of the enzyme expressed in the carcinoma was identified as the brain type. These results warrant further studies on the mechanisms for transporting the large molecule of brain-type glycogen phosphorylase to nuclei and its function in the nucleus of carcinoma cells.

Duodenal Adenoma Removed by Endoscopic Polypectomy

Abstract: We report two duodenal adenoma cases treated by endoscopic polypectomy. Case 1, a 59‐year‐old male, visited our hospital for further examination of a duodenal polyp found elsewhere. X‐ray examination revealed a semi‐pedunculated polyp with an irregular surface in the second portion of the posterior wall of the duodenum. Case 2, a 68‐year‐old male, was admitted to our hospital for endoscopic polypectomy of a duodenal polyp. Upper GI series demonstrated a semi‐pedunculated round polyp with a shallow central depression. Endoscopic polypectomy was performed for both lesions and the polyps were successfully removed. The resected polyps were 11 × 10 mm and 13 × 12 mm in size, respectively. The polyps were histologically diagnosed as tubulovillous and tubular adenomas, respectively, with no evidence of malignancy. Endoscopic polypectomy provides histological confirmation of adenoma of the gastrointestinal tract, and it is frequently applicable to the duodenum.