[A case of inverted papilloma of the renal pelvis, associated with metachronous urothelial carcinoma of the urinary bladder].

The patient visited our hospital because of macrohematuria. Cystoscopical examination did not reveal any bladder tumors but a tumor shadow in the right renal pelvis was revealed by computed tomographic scan. Urothelial carcinoma was suspected and right nephroureterectomy was performed. Pathologically the tumor was diagnosed as inverted papilloma. Four months later during the follow up of the tumor, urothelial carcinoma of the urinary bladder was detected by cystoscopy. Inverted papilloma of the renal pelvis is a rare lesion and only 39 cases to date have been reported. Because inverted papilloma of the upper urinary tract is often associated with other urothelial tumors, careful long-term follow up is advisable.

Hepatic steatosis as a possible risk factor for the development of hepatocellular carcinoma after eradication of hepatitis C virus with antiviral therapy in patients with chronic hepatitis C.

AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (> or = 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre-interferon treatment might be risk factors for developing HCC after SVR.

Angiographic and clinical characteristics associated with the removable plaque components by means of thrombectomy catheters in patients with myocardial infarction.

BACKGROUND: Previous studies have demonstrated that atheroembolism during percutaneous coronary intervention is associated with myocardial damage. The purpose of this study is to investigate the clinical and angiographic characteristics related to removable plaque elements in patients undergoing thrombectomy for myocardial infarction. METHODS: Eighty consecutive lesions in 80 patients (M/F=58/22, age 65.5+/-11.6 years) with myocardial infarction who underwent thrombectomy (TVAC system, Nipro, Osaka, Japan) prior to mechanical dilatation (balloon angioplasty and/or stent implantation) were investigated. Visible debris was collected and plaque elements (cholesterol clefts and/or foamy cells) were investigated pathologically. Baseline angiographic characteristics [baseline thrombolysis in myocardial infarction (TIMI) grade, culprit lesion, haziness, lesion length, ostium, bifurcation, calcification, eccentricity, thrombus, and multivessel] were analyzed, and predictive angiographic and clinical factors for plaque elements were investigated. RESULTS: There were no complications related to thrombectomy. Final TIMI grade 3 and blush grade 2 or 3 were achieved in 75 (94%) and 66 (83%) patients, respectively. Visible debris specimens were obtained in 49 (61%) patients. Histological plaque elements (cholesterol clefts and/or foamy cells) were observed in 27 out of 49 patients with debris specimens. There was no significant difference in the clinical characteristics between the groups of patients with (group P) and without (group NP) plaque elements. Aspirated plaque elements were more frequently observed in discrete and eccentric lesions (group P vs. group NP: discreteness, 52% vs. 28%, P<.05; eccentricity, 67% vs. 36%, P<.05). CONCLUSIONS: This study demonstrated the clinical characteristics associated with removable plaque components in patients with myocardial infarction undergoing thrombectomy by means of the TVAC system. Discreteness and eccentricity were more frequently observed in lesions with removable plaque elements.

Pathogenesis of herpes simplex hepatitis in macrophage-depleted mice: possible involvement of tumor necrosis factor-alpha and inducible nitric oxide synthase in massive apoptosis.

Massive liver cell death provoked in silica-treated mice subsequently infected with herpes simplex virus (HSV)-1 is very similar pathohistologically to the cell death observed in human fulminant hepatitis. Previously, we have shown this liver cell death to be extensive apoptosis. In the present study, we examined various factors related to liver damage patho- and immunologically, as well as by reverse transcription-polymerase chain reaction. Tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), interferon (IFN)-alpha, and interleukin-6 mRNAs were detected to a much greater extent in silica-treated mice compared with control mice after HSV-1 infection, and excessive expression of iNOS mRNA and cytokine mRNAs in the liver may be closely related to massive liver cell apoptosis. The apoptosis was less related to the fas ligand than to TNF-alpha. Silica blockage of macrophages makes the liver cell extremely vulnerable to HSV-1 infection, and it induced expression of E-selectin and neutrophil margination in the liver. Subsequent HSV-1 infection induced excessive production of iNOS and cytokines, particularly TNF-alpha, but administration of anti-TNF-alpha antibody or NG-monomethyl-L-arginine was not completely efficacious for the survival of the mice. Overproduction of free radicals in combination with cytokines, such as TNF-alpha, IL-6 and IFN-alpha, may result in hepatic cell apoptosis.

Prevalence of ischemic enterocolitis in patients with acute pancreatitis.

BACKGROUND: A considerable number of acute pancreatitis cases have been reported to be complicated by nonocclusive mesenteric ischemia. However, no reports have ever referred to the incidence of ischemic enterocolitis in patients with acute pancreatitis, using a series of autopsy cases. Here, we report our review of autopsy cases of patients with acute pancreatitis to examine the incidence of associated ischemic enterocolitis. METHODS: The intestinal and pancreatic slides of 48 autopsy cases of patients with acute pancreatitis were reviewed and the incidence of ischemic enterocolitis was determined. Clinical case records were also reviewed. RESULTS: Thirteen (27%) of 48 autopsy cases of patients with acute pancreatitis were complicated by ischemic enterocolitis. The frequency of shock was significantly higher in patients with ischemic enterocolitis than in those without ischemic enterocolitis. The intestinal lesion was diffuse in many cases and gangrene was not an unusual finding. CONCLUSIONS: The incidence of ischemic enterocolitis in patients with acute pancreatitis was much higher than that in the previous reports. Clinicians who treat patients with acute pancreatitis should consider ischemic enterocolitis as one of the frequent and severe complications of this condition.

Interobserver variation in the histopathological assessment of nonalcoholic steatohepatitis.

Pathological assessment is considered as the gold standard for the diagnosis of nonalcoholic steatohepatitis (NASH). However, there is no agreement of histological features required for the diagnosis of NASH. In the present study, eight experienced hepatopathologists read liver biopsy specimen slides of 21 cases of NASH and suspected NASH independently and were asked to assess histopathological features and render a diagnosis. Interobserver variation among pathologists was evaluated by kappa statistics. Significant, good agreement was present in evaluation of the extent of steatosis and grade of fibrosis. Agreement was moderate concerning the localization of steatosis, localization of fibrosis, and glycogen nuclei. Only slight or poor agreement was seen in evaluation of type of steatosis, ballooning, intralobular necroinflammatory change, portal inflammation, and degree of neutrophilic infiltration. Thus the agreement varied for histological variables. Significant, moderate agreement was seen in the diagnosis of NASH but agreement was poor in the diagnosis of suggestive NASH. The agreement for the diagnosis of NASH was not high as for the individual histological findings that were thought to be the basis of the diagnosis. In conclusion, some histological features in NASH might prove useful for the development of a standardized and reliable pathological diagnosis and scoring system.

Right axillary lymph node metastasis of carcinoma of the cecum with histologically proven cutaneous lymphatic invasion by carcinoma cells: a case report.

Axillary lymph node metastasis from colorectal carcinoma is extremely rare, and this scarcity hinders understanding of its pathogenesis and, thus, the application of appropriate management. Here, we present a case with axillary lymph node metastasis of cecal carcinoma associated with macroscopic invasion of the skin of the abdominal wall with histological evidence of such invasion, findings which support our hypothesis that the axillary lymph node metastasis developed via the lymph channels in the skin of the abdominal wall. A 76-year-old woman with cecal carcinoma (T4N1M0), complicated with an abdominal wall abscess, underwent right hemicolectomy with partial resection of the abdominal wall. Histology demonstrated multiple sites of lymphatic invasion in the skin. Two months later, an enlarged right axillary lymph node was noticed on CT, and an excisional biopsy was obtained, which later confirmed metastatic adenocarcinoma. This is the first case report of axillary lymph node metastasis of carcinoma of the cecum with histologically proven invasion via the lymphatic system in the skin. If axillary lymph node metastasis results from aberrant lymphatics due to invasion from an adjacent organ, and not the result of systemic malignant disease, it may be considered as a surgically curable pathology. Therefore, the authors advocate that patients with axillary lymph node metastasis should be evaluated with regard to the possibility of surgical curability.

Hepatitis B and C virus infection and p53 mutations in human hepatocellular carcinoma in Harbin, Heilongjian Province, China.

To clarify the importance of hepatitis B (HBV) and C virus (HCV) infection and p53 gene mutation in the genesis of hepatocellular carcinoma (HCC), we investigated DNA samples of formalin-fixed paraffin-embedded HCC tissue specimens from patients in the North China area of Harbin, Heilongjian province. Fifty-eight DNA samples from 43 cases obtained during surgery and the remaining 15 autopsy materials were analyzed by polymerase chain reaction (PCR) about HBV and HCV. The p53 gene (exon 7) mutant testing, in addition, was performed by PCR-direct sequencing. Histopathologically, we determined the histological grade of HCC in all specimens. Forty-five (77.6%) of 58 cases were HBV DNA-positive; only two (3.4%) HCV RNA-positive cases were found. Two of 37 samples screened showed a point mutation (AGG to AGT) at codon 249, the exon 7 hot spot of the p53 gene. The fact implies that HBV plays a very important role, but aflatoxin B1 is not an important factor in the genesis of HCC in Harbin, Heilongjian district, People's Republic of China.

Ceroid accumulation in rat kidneys caused by uptake of ferric nitrilotriacetate.

Ceroid accumulation in kidneys caused by lipid peroxidation in vivo was studied during intraperitoneal (i.p.) injections of ferric nitrilotriacetate (Fe3+-NTA) solution, which is a weak iron chelate compound and generates free radicals in the presence of oxygen. Fe3+-NTA solution (0.5-0.75 mg/100 g body weight) was injected into rats (n=6) for 4 days a week. After 2 weeks of Fe3+-NTA loading, the rats were not treated for 1 month as a rest interval, and then the iron loading was repeated for 35 weeks including the rest intervals. Two rats in each group, Fe3+-NTA loading and control, were sacrificed at 19 and 40 weeks of age, and portions of a kidney and the liver of each rat were fixed in 10% formalin buffered to pH 7.0 for the histological studies. We found ceroid accumulates in greater amounts and more quickly within macrophages and epithelial cells of proximal convoluted tubules of the kidney and Kupffer cells of the liver in iron-loaded rats.

Age-associated decrease in 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivity in the autopsied brain.

The 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a DNA base modified by reactive oxygen species (NOS). The 8-OHdG has been shown to be generated in the brain during ischemia-reperfusion. We performed the immunohistochemical study of 8-OHdG in the brains of autopsied specimens. Age had a statistically significantly negative correlation with 8-OHdG immunoreactivity in glial cells. The 8-OHdG immunoreactivity in glial cells was not increased in the surrounding border of the infarction compared with the non-ischemic areas in the same cases. There was no statistically significant difference in the disease-free areas between infarction and the age-matched control cases. This indicates that 8-OHdG immunoreactivity may not be a sensitive tool to evaluate the infarction injury in human autopsied specimens.

High expression of eosinophil chemoattractant ecalectin/galectin-9 in drug-induced liver injury.

BACKGROUND: Ecalectin/galectin-9 (ECL/GL9) is an eosinophil chemoattractant isolated from T lymphocytes. Drug-induced liver injury (DILI), often caused by an allergic mechanism, is occasionally accompanied by eosinophilic infiltration. In this study, we intended to determine whether DILI can induce augmentation of ECL/GL9 expression. Further, we investigated whether this augmentation is associated with tissue eosinophilia. METHODS: We examined the expression of ECL/GL9 in biopsy specimens of DILI using the immunohistochemical technique. A rabbit anti-ECL/GL9 antibody was produced by immunizing rabbits with synthetic peptide corresponding to a molecular epitope of ECL/GL9. Thereafter, immunohistochemical staining with the use of this antibody was performed on 16 DILI needle biopsy specimens, and on biopsy specimens of chronic viral hepatitis, liver cirrhosis, and normal liver tissues as controls. RESULTS: In all cases of DILI specimens, but not in control liver specimens, a clear positive staining for ECL/GL9 was observed. Such positive staining was noted on Kupffer cells, fibroblasts, and histiocytes, but not on lymphocytes or hepatocytes. However, the intensity of immunolabeling did not correlate with the extent of eosinophile leukocyte infiltration. CONCLUSION: High expression of ECL/GL9 is suggested to be a specific finding of DILI. However, tissue eosinophilia in DILI cannot be explained by the augmentation of ECL/GL9 expression.

Apoptosis in murine lymphoid organs following intraperitoneal administration of dimethyl sulfoxide (DMSO).

A significant increase in lymphocyte apoptosis was detected by the TUNEL method in the thymus, spleen, and Peyer's patches (PP) following intraperitoneal (i.p.) administration of dimethyl sulfoxide (DMSO) (treatment, n = 47; control, n = 8). Interestingly, administration of low doses of DMSO caused apoptosis in only the PP, and suggested that i.p. administration of DMSO induced apoptosis for each lymphoid organ in a dose dependent manner. Moreover, in the early stage during the apoptotic change, a characteristic localization of lymphocytes undergoing apoptosis was observed. Briefly, early apoptosis occurred predominantly in the cortical mid-zone of the thymus, white pulp of the spleen, and germinal centers of PP. With increased time following administration, however, lymphocytes throughout lymphoid tissues, independent of characteristic localization during the early stage, seemed to undergo apoptosis, resulting in the severe loss of lymphocytes. In fact, the relative spleen weight significantly decreased at 24 h following DMSO administration (n = 7; P < 0.001 versus 8 control mice). Taken together, these results showed for the first time that the in vivo administration of DMSO to mice caused apoptosis in lymphoid organs, and also demonstrated that the apoptotic behavior varied between different lymphoid organs.

Sarcomatoid carcinoma with components of small cell carcinoma and undifferentiated carcinoma of the gallbladder.

We report a case of sarcomatoid carcinoma with components of small cell carcinoma and undifferentiated carcinoma of the gallbladder. An 84-year-old woman was admitted to our university hospital with right upper abdominal pain and back pain. Clinical diagnosis of a gallbladder tumor was made based on the findings of abdominal ultrasonography, computed tomography and endoscopic retrograde cholangiopancreatography, and a cholecystectomy was carried out. On gross examination a pedunculated polypoid tumor protruded into the lumen of the gallbladder. Histologically the tumor was composed of carcinomatous and sarcomatous components; the carcinomatous component consisted mainly of small cell carcinoma and undifferentiated carcinoma. In general, the carcinomatous component of sarcomatoid carcinoma of the gallbladder consists of adenocarcinoma, and there have only been two previously reported cases in which the carcinomatous component consisted of small cell carcinoma or undifferentiated carcinoma. Because the patient's prognosis may be influenced by the peculiar carcinomatous component in such cases, it is important to accumulate case reports that clarify their clinicopathological features.

The role of donor CD4(+) T cells in the reconstitution of oral immunity by herpes simplex virus type 1 in severe combined immunodeficiency mice.

Severe combined immunodeficiency (SCID) mice with ill-developed Peyer's patches develop neither antibodies nor protection against lethal herpes simplex virus type 1 (HSV-1) infection by oral immunization. However, SCID mice carrying spleen cells from immunocompetent BALB/c mice had serum anti--HSV-1 antibody; anti--HSV-1 IgA antibody was detected in eye wash samples, and the mice were protected against lethal HSV-1 infection (88% survival rate). Western blotting showed that antibodies in SCID mice carrying spleen cells from BALB/c mice recognized 60-kDa HSV-1. The effector cells in transferred spleen cells were CD4(+), not CD8(+), T cells. Donor T cells were detected in the submucosal layer of the gut in SCID mice 1 day after transfer. Rapid movement of donor T cells to the gut may have a role in mucosal immunity to HSV-1. Thus, the normal environment for mucosal immunity develops in SCID mice without prior presence of CD4(+) T cells.

Myolipoma of the retroperitoneum.

A case of retroperitoneal myolipoma is reported. A 55-year-old woman with the main complaint of an abdominal mass was admitted to Teikyo University Hospital, Tokyo, Japan. Retroperitoneal liposarcoma was suspected based on magnetic resonance imaging, and the tumor was resected. The resected tumor was well encapsulated and 30 x 15 x 8 cm in size. Histologically, it consisted of mature adipose cells and smooth muscle cells. Neither nuclear atypia nor mitosis was observed in either component. The tumor was pathologically diagnosed as myolipoma of the retroperitoneum. Retroperitoneal myolipoma is often misdiagnosed radiologically as liposarcoma because the overwhelming majority of large retroperitoneal tumor containing fat is liposarcoma, however, the clinical course of myolipoma is quite different from that of liposarcoma. Although myolipoma is very rare, pathologists should consider it in the differential diagnosis of fat-containing retroperitoneal masses.