Role of Necl-5 in the pathophysiology of colorectal lesions induced by dimethylhydrazine and/or dextran sodium sulphate.

Necl-5 is an immunoglobulin-like molecule that was originally identified as a poliovirus receptor. Although Necl-5 expression is often up-regulated in cancer cells, its pathophysiological significance in the development of cancer remains unclear. We investigated the roles of Necl-5 in the development of colitis-associated neoplasia. Necl-5-deficient mice were generated and treated with dimethylhydrazine (DMH) and/or dextran sodium sulphate (DSS) to induce colitis and its associated neoplasias. Colon tissues were examined for histology, Ki-67 expression by immunohistochemistry and K-ras gene mutation. Colon tumours occurred significantly less frequently in heterozygous (Necl-5(+/-)) or homozygous Necl-5-deficient (Necl-5(-/-)) mice than in wild-type (WT) mice with DMH/DSS treatment. Total ulcer index and inflammatory cell infiltration were significantly lower in Necl-5(-/-) mice than in WT mice with DSS alone or DMH/DSS treatment. Colon tumours in both WT and Necl-5(-/-) mice showed high cell proliferation ability but lacked K-ras mutation. The total Ki-67 labelling index in non-neoplastic colon epithelium was significantly higher in WT (45.9 +/- 0.94) than in Necl-5(+/-) (34.3 +/- 1.40) or Necl-5(-/-) (27.7 +/- 1.15) mice with DMH/DSS treatment (p < 0.001). Necl-5 plays a role in the development of colitis-associated cancer by up-regulating colonic mucosal cell proliferation.

Histopathogenesis of intestinal metaplasia: minute lesions of intestinal metaplasia in ulcerated stomachs.

Minute lesions of intestinal metaplasia composed of a few metaplastic tubules were observed in the gastric mucosa during routine histological examination of gastrectomy specimens. The histological findings indicated that these lesions might be an initial stage of more advanced intestinal metaplasia. Accordingly, more than 18,000 serial sections in 10 stomachs with chronic ulcers were examined to clarify the histopathogenesis of the intestinal metaplasia. It was concluded from the three dimensional reconstruction of minute intestinal metaplasia lesions that these lesions originated during the regenerative process of healing of gastric erosions. The lesions were roughly globoid with a depression on the surface. It is thought that with continuous formation and healing of gastric erosions, more extensive intestinal metaplasia lesions would be formed by an increase in size and confluence of these focal minute intestinal metaplasia lesions.

Ultrastructural study of two subtypes of gastric adenoma.

An ultrastructural study was performed to identify any differences in fine detail between type III and IV gastric polyps, which seem to differ from each other because they have different histological features and malignant potential. Clear ultrastructural differences were found, implicating microvilli, mucous granules, interdigitations, ribosomes, mitochondria and nuclei. Although these two subtypes have often been grouped together as borderline lesions or adenomas, the findings imply that they should be treated as essentially different.

Clinical importance of DNA content in rectal cancer measured by flow cytometry.

The DNA content of 369 rectal cancers was measured by flow cytometry. One hundred and four (28%) were diploid, 252 (68%) were aneuploid, and 13 (3.5%) were tetraploid. Diploid cancers were associated with an improved 5 year survival (p less than 0.001) and were more likely to present at an early stage. DNA content, however, did not confer independent prognostic information in a Cox model based on four discrete pathological variables. Patients were classified by a new system of prognostic grouping and those with a very good or a very poor outlook were removed leaving 137 prognostic group III patients. No further substratification of this group by DNA content or by four additional pathological variables could be achieved. As the new prognostic system is not improved by the addition of ploidy, routine adoption of flow cytometry in the assessment of rectal cancer cannot be recommended.

Changes in serum C-reactive protein levels in dogs with various disorders and surgical traumas.

The serum levels of C-reactive protein (CRP) produced as an inflammatory response in dogs with various disorders and surgical traumas were measured by enzyme-linked immunoabsorbent assay and slide reversed passive latex agglutination test (RPLA). The CRP levels were greatly increased 1-2 days after surgery in most of the dogs (n = 29) subjected to surgery. These levels had markedly decreased by the time the sutures were removed. In dogs with various disorders (n = 58), the serum CRP levels at first diagnosis were high in infectious diseases. In dogs from which paired serum samples were examined, the serum CRP usually showed a decrease with improvement in the condition (n = 11) or a terminal increase (n = 4) but, conversely, some showed an increase with improvement in the condition (n = 3).

[Clinical significance of DNA content of rectal cancer measured by flow cytometory].

DNA content of 369 rectal cancers was measured by flow cytometry. One hundred and four (28.2%) were diploid, 252 (68.3%) were aneuploid and 13 (3.5%) were tetraploid. Diploid cancers were associated with an improved 5 year survival (p less than 0.001) and were more likely to be diagnosed at an early stage. However DNA content did not confer independent prognostic information in a Cox model based on four discrete pathological variables. Patients were classified by a new system of prognostic grouping and those with a very good or a very poor outlook were removed leaving 137 prognostic group 3 patients. No further substratification of this group by DNA content or by four additional pathological variables could be achieved. As the new prognostic system is not improved by the additional of ploidy, routine adoption of flow cytometry in the assessment of rectal cancer can not be recommended.

[Histopathogenesis of intestinal metaplasia--minute lesions of intestinal metaplasia in the ulcer-bearing stomach].

More than 18,000 serial sections were performed in 10 ulcer-bearing gastrectomy specimens with mild intestinal metaplasia and containing minute lesions of intestinal metaplasia composed of a few metaplastic tubules, which often had an onion skin-like appearance. Fifty-two minute lesions could be reconstructed and examined three-dimensionally in these serial sections. As a result of this study, these minute lesions showed, without exception, a very close resemblance to a hen's egg or globe and had a dimple at the center. Moreover, we could detect minute lesions of intestinal metaplasia in which erosion and indifferent epithelia coexisted. From the various circumstantial findings, it was demonstrated that these lesions originated in the regenerative process of erosions.

Wound healing and complications of the liver after percutaneous transhepatic cholangiography.

A total of 10 autopsy cases who had received percutaneous transhepatic cholangiography (PTC) were examed and analysed from the view point of chronological changes of hepatic damage caused by the puncture. The conclusion obtained on the process of simple healing can be summarized as follows: (1) Hemocoagulation or hematoma formation on the hepatic surface and intra-peritoneal hemorrhage were seen until the 7th day after PTC but not in cases of the 13th day or later, while the scar of puncture was recognizable on the hepatic capsule in cases of up to the 16th day but was not remaining in ones of the 41st day and later. (2) Damage of the hepatic parenchyma was existing until the 7th day, which, however, was repaired by the 13th day. (3) Intra-hepatic hematoma was seen until the 13th day but faded away thereafter. Namely, intrahepatic trauma caused by PTC seems to be completely cured without leaving any scar in about a half month. However, the puncture trace on the diaphragm was seen in one case of the 42nd day after PTC examination, therefore the nature of diaphragmatic trauma seems to be somewhat different from that of the liver, including its capsule. Besides, discussions are also made on some hepatic complications caused by PTC, as well as on clinical significance of this kind of pathomorphological study.

Fourier analysis of broad spectral EEG from a fluctuation point of view.

It is believed that the EEG is the most reliable method of evaluating brain function, but neither quantitative nor qualitative studies of the EEG have been carried out over the entire range of frequencies. Analysis of limited frequency bands of the EEG has not disclosed the whole of neuronal activity. The aim of this study is to clarify the upper limit of EEG frequency. Our EEG analytic system is composed of a high fiedlity preamplifier and signal processor with a frequency response within -3 dB below 20 kHz. Thirty adult cats were used for these experiments. The upper limit of the frequency varied in different structures: 6.9 +/- 0.8 kHz (+/- SEM) in motor cortex, 4.1 +/- 0.3 kHz in the hippocampus, 2.9 +/- 0.5 kHz in the amygdala, 9.3 +/- 0.6 kHz in the ventrolateral nucleus of the thalamus, and 9.9 +/- 0.5 kHz in the midbrain reticular formation. Three different types of amplitude spectra were characterized in bilogarithmic graphs. These types are named types f, f + L, and L corresponding to 1/f or Lorentzian fluctuation. In conclusion, the upper limit of frequency and the spectral types correspond to the neuronal specificity of different brain regions. Their physioanatomic significance is discussed.

Comparing the treatment outcomes of endoscopic papillary dilation and endoscopic sphincterotomy for removal of bile duct stones.

To compare the clinical usefulness of endoscopic papillary dilation (EPD) and endoscopic sphincterotomy (EST) for removal of bile duct stones, 110 patients with stones up to 15 mm in diameter and less than 10 in number were randomly treated with either EPD (55 patients) or EST (55 patients). The patients were followed up for a median period of 23 months and endoscopic manometry with the administration of morphine was carried out in 17 patients who were observed more than 12 months after the procedures to evaluate the post-procedure papillary function. Duct clearance was achieved in 51 EPD (92.7%) and 54 EST patients (98.1%, not significantly different). Forty EPD (78.4%) and 51 EST patients (94.4%) achieved duct clearance in the initial procedure (P=0.02). Early complications occurred in one EPD (2.0%) and in three EST patients (5.6%, P=0.62). Complications during the follow-up period occurred in two EPD and eight EST patients. Recurrence of bile duct stones was observed in two EPD and three EST patients (P=0.98). Acute cholecystitis was observed in one EPD and five EST patients (P=0.06) and among patients with gall-bladder stones in situ, the rate of acute cholecystitis after EPD was significantly lower than that after EST (P=0.03). Endoscopic manometry showed the existence of a choledochoduodenal pressure gradient only after EPD, while papillary contractile function was observed after both procedures. In conclusion, both EPD and EST are safe therapeutic modalities, although EPD is more clinically effective in decreasing the risk of acute cholecystitis in patients with gall-bladder stones in situ and in preserving post-procedure papillary function.

Long-term survival of a patient with bile duct carcinoma by endoscopic biliary drainage.

An 80-yr-old female presented with obstructive jaundice. Endoscopic retrograde cholangiopancreatography showed a carcinoma in the middle extrahepatic bile duct, and a biliary endoprosthesis was inserted. Exfoliative cytology of the bile and forceps biopsy of the tumor revealed a papillary adenocarcinoma. Surgical resection could not be done because of her cardiovascular complications, and neither chemotherapy nor radiotherapy was administered. Stents were exchanged and cleaned 21 times because of occlusion and cholangitis. Subsequent serial cholangiogram showed a slow growth of the papillary tumor, but local invasion to the adjacent organs or distant metastasis was not observed. The patient survived for 7 yr and 6 months after insertion of the biliary endoprosthesis.

Adenocarcinoma arising at the perineal wound after pull-through procedure for imperforate anus.

An extremely rare case is presented here, of an adenocarcinoma at the site of a long-standing perineal wound, the presence of which was a result of a pull-through procedure for imperforate anus. Wide local excision of a huge mass, including the perineal skin and the distal rectosigmoid segment, was carried out en-bloc on a 35 year old male. This tumor may have been caused by the repeated trauma and frequent ulceration around the perineal wound as a result of poor hygiene due to a fecal incontinence.

Do aggressive subclones within primary colorectal cancer give rise to liver metastases?

Primary colorectal cancers and hepatic metastases from 24 patients have been compared according to type, grade, DNA content as measured by flow cytometry, and expression of two differentiation antigens and carcinoembryonic antigen (CEA). The primary and secondary tumours were histologically indistinguishable in 23 out of 24 cases. DNA content differed between primary and metastasis in only six cases. Immunohistochemical profiles were usually the same in the primary and metastasis. In particular, heterogeneous expression by the primary was mirrored in the metastasis. In 17 out of 24 (70.1%) patients the primary and metastasis were indistinguishable by all six parameters. In one of these, the liver metastasis had been removed 14 years 10 months after the primary tumour. It is concluded that DNA content as measured by flow cytometry may remain stable for long periods and that the differences shown in this study may simply be due to inadequate sampling of the primary tumour. Phenotypic heterogeneity may be epigenetic and not indicative of genetic instability and cannot be used to track the progression of subclones.

Case report: a case of primary ileal carcinoma in a young woman and a review of the Japanese literature.

We report a case of primary ileal carcinoma in a young woman, which was diagnosed definitively before operation. A 29-year-old woman presented with abdominal pain, diarrhoea and bloody stools. Colonoscopic and radiographic studies revealed that there was a 7.5 x 7 cm tumour (well-differentiated adenocarcinoma) at the terminal ileum, forming an ulcerated lesion at the centre. The tumour had invaded the caecum, the right urinary tract, the right ovary and a portion of the sigmoid colon. Fifty-three cases of primary ileal carcinoma were reported in Japan between 1982 and 1994 and their clinical features are reviewed herein.

Endoscopic pancreatic sphincter balloon dilation for effective retrieval of pancreatic duct stone.

To facilitate pancreatic stone retrieval, four patients with chronic pancreatitis and pancreatic stones underwent endoscopic pancreatic sphincter balloon dilation (EPSBD) rather than pancreatic sphincterotomy. Extracorporeal shock wave lithotripsy combined with endoscopic removal was carried out in three patients. Stone removal following EPSBD was completely successful in all four patients. Patients showed no severe complications during the dilation procedure. In one patient, to prevent pancreatitis, an endoscopic nasopancreatic drain was placed for 1 week after EPSBD. Compared with pancreatic sphincterotomy, EPSBD can be performed safely in patients with chronic pancreatitis to assist in the extraction of pancreatic duct stones. Use of the EPSBD procedure in cases of chronic pancreatitis provides a useful approach to improve endoscopic clearance of pancreatic duct stones.

Reduced expression of p53 and cyclin A in intraductal mucin-hypersecreting neoplasm of the pancreas compared with usual pancreatic ductal adenocarcinoma.

OBJECTIVE: Intraductal mucin-hypersecreting neoplasm (IMHN) of the pancreas, a slow-growing malignancy with a favorable prognosis, is distinctly categorized from the high-grade malignancy of the more common ductal adenocarcinoma. The aim of the present study was to clarify the molecular differences underlying the biological differences between IMHN and ductal adenocarcinoma of the pancreas. METHODS: The expression of p53 and cyclin A in IMHN was compared with that in ductal adenocarcinoma of the pancreas immunohistochemically. RESULTS: In IMHN, the incidence of p53 and cyclin A ascertained by positive nuclear staining was significantly lower than that in ductal adenocarcinoma. Furthermore, in ductal adenocarcinoma, p53 and cyclin A are topographically coexpressed. CONCLUSIONS: These results suggest that the overexpression of p53 and cyclin A plays a role in the tumorigenesis of pancreatic ductal adenocarcinoma, and sparse expression of both antigens in IMHN may partly contribute to its low-grade malignant characteristics.

Case report: Pneumatosis cystoides intestinalis associated with post-surgical bowel anastomosis: a report of three cases and review of the Japanese literature.

We report three cases of pneumatosis cystoides intestinalis (PCI) occurring in association with post-surgical bowel anastomosis. A 74-year-old man, a 58-year-old woman, and a 62-year-old woman were found to have PCI at the colonic side of a bowel anastomosis at 4 years, 3 years and 1 year after operation, respectively, for right colon carcinoma, although all were asymptomatic. They all had a positive anti-nuclear antibody test and had received postoperative cancer chemotherapy. The clinical features of 123 cases of PCI reported in Japan between 1981 and 1995 were also reviewed. On the basis of the present and previous cases, we propose that post-surgical anastomosis, cancer chemotherapy, and predisposition to collagen vascular disease might be responsible for the damage to intestinal mucosa that leads to the development of PCI.

Comparative study of CA242 and CA19-9 in chronic pancreatitis.

CA242 has been proved to be useful in the diagnosis of pancreatic cancer. The aim of the present study was to clarify the mechanisms contributing to the high specificity of CA242 as compared with CA19-9 resulting from scarce serum elevation of this antigen in patients with chronic pancreatitis by correlating serum levels and endoscopic retrograde choledocho-pancreatography (ERCP) findings and by immunohistochemical analysis. Serum CA19-9 levels were significantly elevated in patients with calcification and with main pancreatic duct (MPD) stenosis or obstruction. On the other hand, serum CA242 levels showed no significant elevation in patients with such factors. Even though such pathological conditions were considered to lead to the stagnation of pancreatic juice, serum CA242 levels seemed to be less affected than serum CA19-9 levels. Immunohistochemical studies of chronic pancreatitis tissues revealed that CA242 was expressed less frequently and less intensely than CA19-9, and the difference in expression was more prominent in the centroacinar cells and terminal ductules. From the results of the present study, it is conceivable that CA242 is less influenced by the stagnation of the pancreatic juice than CA19-9 because of the low levels of expression in ductal systems, which results in the release of this antigen into the circulation in lower amounts than that of CA19-9.