Co-registered positron emission tomography/computed tomography and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging features of multiple angiosarcoma of the liver.

Hepatic angiosarcoma is a very rare disease, accounting for only 2% of primary liver malignancy. An 82-year-old man was admitted to our hospital because of jaundice and weight loss. Computed tomography (CT) and magnetic resonance imaging (MRI) showed diffuse and multiple space-occupying lesions. On gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, the tumor was not enhanced intensely in the arterial phase following contrast injection, and was then gradually enhanced homogeneously. In the delayed phase and hepatobiliary phase, the tumor was completely washed out. Whole-body (18) F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT fusion scanning confirmed metabolic activity with maximum uptake value of 3.64 in the lesions. A liver biopsy showed spindle-shaped tumor cells proliferating along sinusoids, with elongated and hyperchromatic nuclei. Immunohistochemical studies showed tumor cells positive for von Willebrand factor and CD34. These findings were consistent with angiosarcoma of the liver. This case report is the first description of co-registered FDG-PET/CT images and Gd-EOB-DTPA-enhanced MRI of primary hepatic angiosarcoma.

Lymphatic tumor emboli detected by D2-40 immunostaining can more accurately predict lymph-node metastasis.

BACKGROUND: Resected specimens of superficial squamous cell carcinoma of the esophagus (SSCCE) underwent D2-40 immunostaining to accurately assess lymphatic tumor emboli (LY) and to analyze correlations between LY and lymph node metastasis (N). This present study was designed to determine the accuracy of LY grade for predicting the risk of N. MATERIALS AND METHODS: We studied 75 patients with SSCCE who underwent surgical resection of their tumors. Resected specimens were sliced into continuous sections at 5 mm intervals. Intramucosal cancers are classified into three groups (m1, m2, m3), and submucosal cancers are also divided into three groups (sm1, sm2, sm3). The numbers of LY present in lymphatic ducts on D2-40 immunostaining, venous tumor emboli (V) on CD34 immunostaining, and lymphatic tumor emboli (ly) and V on hematoxylin-eosin staining (HE) and elastica van Gieson staining (EVG) were counted for each case. The presence of lymphatic tumor emboli was graded according to the total number of LY per case as follows: 0, LY0; 1 to 2, LY1; 3 to 9, LY2; and 10 or more, LY3. RESULTS: All m1 and m2 cases were LY- and N- Lymphatic tumor emboli were present in 54% of m3 cases, 70% of sm1 cases, 54% of sm2 cases, and 75% of sm3 cases. Determination of N was positive in 18% of m3 cases, 47% of sm1 cases, 36% of sm2 cases, and 62% of sm3 cases. The frequency of LY significantly correlated with the number of N (p < 0.0001). Multiple regression analysis showed that only LY and V significantly correlated with N. When the detection rate of N was compared between LY and ly, LY was superior to ly in terms of specificity, accuracy, positive predictive value, and false positive rate. As for LY grade, N was positive in 39.1% of LY1 cases, 81.8% of LY2 cases, and 100% of LY3 cases. Even in LY-, N was positive in one sm1 case and in two sm2 cases. In the sm1 case, the depth of invasion was 350 µm from the lower margin of the muscularis mucosae. CONCLUSIONS: Evaluation of lymphatic invasion on the basis of LY is more accurate for the prediction of N than conventional techniques, and LY grade strongly correlates with N. In patients with SSCCE, mucosal cancers (m1, m2, and m3) and submucosal cancers with a depth of invasion of ≤ 200 µm from the lower margin of the muscularis mucosae on endoscopic mucosal resection have a low risk of N if the number of LY is 0. Endoscopic mucosal resection alone can provide good treatment outcomes in such patients.

Immunohistochemical, molecular, and clinicopathological analyses of urothelial carcinoma, micropapillary variant.

The prognosis of urothelial carcinoma, micropapillary variant (MPV), of the bladder has been shown to be worse than that of the conventional urothelial carcinoma (UC). However, it remains to be clarified why the MPV is more aggressive. We therefore here focused on the correlation between clinical features and histological, immunohistochemical and molecular findings for eight MPV and 35 UC, evaluating expression of MUC1, Ki-67, p53, CD147, CD34, D2-40, and extracellular matrix proteins. The Ki-67 labeling index was significantly higher in UC than in MPV but densities of venous and lymphatic tumor emboli were significantly higher in the MPV cases and lymph node metastasis was more frequent, with a poorer prognosis. Tenascin-C and fibronectin also showed significantly greater expression in MPV than in UC at the epithelial-mesenchymal interfaces. Direct sequencing showed point mutations of KRAS exon 1 in three MPV with significantly more frequency compared to UC. Occupation rate of the MPV area in the tumor showed significant inverse correlation with overall survival. Thus our histopathological findings provide clues to explaining why prognosis is poorer in the MPV than UC.

Acute intrahepatic cholestasis accompanied with Chlamydophila pneumoniae infection.

We report a case of Chlamydophila (C.) pneumoniae infection presenting with fever and rapid intrahepatic cholestasis. A 63-year-old man had a week-long history of intermittent high fever and rapidly progressive jaundice with atypical erythema. The results of liver function tests were recorded. The results of all serological tests were negative; the IgM, IgG, and IgA titers for C. pneumoniae had increased, which indicates a C. pneumoniae infection. The patient's fever and liver dysfunction improved upon administration of minocycline. Light microscopic findings showed the presence of enlarged liver cells with clear cytoplasm, a few mitotic figures, multinucleated cells, and bile cholestasis. The electron microscopic appearance of liver biopsy showed that bile canaliculi exhibited intrahepatic forms of cholestasis. From the results of light and electron microscopy, we inferred atypical intrahepatic cholestasis, probably resulting from the C. pneumoniae infection.

Cartilage-hair Hypoplasia Complicated with Liver Cirrhosis Due to Chronic Intrahepatic Cholestasis.

We herein report a rare case of cartilage-hair hypoplasia (CHH) complicated with liver cirrhosis. A 20-year-old Japanese man with CHH was found incidentally to have liver cirrhosis and an esophageal varix. This patient had been treated for infections due to immunodeficiency since early childhood. He ultimately died of liver failure at 31 years of age. An autopsy revealed an abnormality of the interlobular bile ducts and intrahepatic cholestasis. Liver cirrhosis was thought to have been caused by chronic intrahepatic cholestasis due to biliary duct hypoplasia and changes in the intestinal microbiome. Therefore, CHH may cause biliary cirrhosis due to multiple effects.

Prostate carcinoma with neuroendocrine differentiation successfully treated by early detection with imaging examination.

INTRODUCTION: Clinicopathological features of neuroendocrine differentiation of prostate carcinoma have not been totally clarified yet. It is known to be associated with poor prognosis. CASE PRESENTATION: A patient with growing prostate-specific antigen was diagnosed with prostate carcinoma and treated by laparoscopic prostatectomy. The pathological examination revealed the neuroendocrine differentiation of the tumor. Early detection of prostate carcinoma with neuroendocrine differentiation can be difficult due to its low expression of prostate-specific antigen. The imaging examination contributed to the early detection. In the follow-up period of 2 years, the patient remains cancer free. CONCLUSION: Recently, the treatment options for prostate carcinoma have been expanded. Precise assessment of immunohistochemical nature of the tumor may be helpful for individualized decision-making.

A case of primary hepatic mixed neuroendocrine-non-neuroendocrine tumor (MiNEN) associated with gallbladder carcinosarcoma.

A woman in her seventies visited our hospital because of abdominal pain. Multiple hepatic tumors were detected and a liver biopsy revealed mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), which was composed of cholangiocellular carcinoma and neuroendocrine tumor (NET). Diagnostic imaging ruled out primary malignancies other than the liver and identified that the tumor originated from the liver. Because a predominant and aggressive part of the tumor was considered to be cholangiocellular carcinoma, gemcitabine and S-1 were used as first-line treatment. After the treatment, octreotide acetate was administered for the NET component, followed by transcatheter arterial embolization. Subsequently, her gallbladder (GB) rapidly swelled with biliary tract obstruction, and cholecystectomy revealed carcinosarcoma of the GB. She is still undergoing treatment at 44 months after diagnosis. Herein we report this case of primary hepatic MiNEN consisting of cholangiocarcinoma and NET, followed by GB carcinosarcoma. This is the first case illustrating that a multidisciplinary treatment approach for MiNEN accompanied with carcinosarcoma, involving assessment and treatment targeting the most aggressive component, can result in a long survival time.

Transperineal ultrasound predicts endoscopic and histological healing in ulcerative colitis.

BACKGROUND: Transabdominal ultrasound is useful to assess inflammation in patients with ulcerative colitis (UC); however, the assessment of the rectum is challenging and a barrier for its widespread use. AIM: To evaluate if transperineal ultrasound is useful for predicting endoscopic and histological findings of the rectum in UC. METHODS: Fifty-three consecutive adults with UC who required colonoscopy were included and transperineal ultrasound was performed in combination with transabdominal ultrasound within a week before or after colonoscopy with rectal biopsy. Mayo endoscopic subscore (MES) ≤1 was defined as endoscopic healing and Geboes score <2.1, Robarts histopathology index ≤6, and Nancy index ≤1 were defined as histological healing. Limberg score and bowel wall thickness were recorded with transperineal ultrasound. Faecal calprotectin was also measured. RESULTS: Excellent correlation was confirmed between colonoscopy and transabdominal ultrasound in all segments except for the rectum. Rectal bowel wall thickness and Limberg score in transperineal ultrasound well correlated with rectal MES and histological indices. Bowel wall thickness ≤4 mm predicted endoscopic (Area under the curve [AUC] = 0.90) and histological (AUC = 0.87-0.89) healing. In multivariable logistic regression analysis, only bowel wall thickness in transperineal ultrasound was a significant independent predictor for rectal endoscopic and histologic healing (P < 0.05) and the predictability was better than faecal calprotectin. CONCLUSIONS: Transperineal ultrasound predicts endoscopic and histological healing of the rectum. The combination of transperineal ultrasound with transabdominal ultrasound visualises the entire colorectum and is an ideal modality for the treat-to-target strategy. Clinical Trials Registry number UMIN000033611 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038323).

Resection of intra-pulmonary endometriosis by video-assisted thoracoscopic surgery under pre-operative CT-guided marking synchronized with menstrual cycle.

A 37-year-old woman experienced repeated catamenial hemoptysis. She had a history of intrauterine curettage. Computed tomography (CT) showed ground glass opacity (GGO) in the right upper lung lobe. We suspected pulmonary endometriosis and scheduled surgery coincides with her menstrual cycle. Then she underwent surgical resection after pre-operative CT-guided marking of the pulmonary endometrial lesion. A yellowish change of the pleura was observed near the marking and the lesion was resected using video-assisted thoracoscopic surgery. Histopathologically, endometrial glands and intimal interstitium were evident. She has no symptoms 2.5 years after surgery. In this case, scheduling the surgery at the time of her menstrual period and video-assisted thoracoscopic surgery (VATS) after CT-guided marking facilitated effective resection.

A Resected Gallbladder Carcinoma Coexisting With Adenomyomatosis Involving Varied Degrees of Intraepithelial Dysplasia: A Case Report and Literature Review.

A 59-year-old asymptomatic man underwent ultrasonography, which revealed gallstones and thickened gallbladder wall. Abdominal computed tomography (CT) showed a slightly swollen bilocular gallbladder and a soft tissue mass in the fundus site. Segmental adenomyomatosis (ADM) was suspected because numerous fundic cystic lesions were seen on magnetic resonance imaging. Endoscopic ultrasonography revealed numerous Rokitansky-Aschoff sinuses (RAS) and a papillary soft tissue shadow surrounded with irregular and remarkably thickened fundic gallbladder wall. Fluoro-2-deoxy-D-glucose-positron emission tomography/CT demonstrated slightly increased fluoro-2-deoxy-D-glucose uptake in the corresponding lesion. Surgery was performed under a diagnosis of gallbladder carcinoma (GBC) with concomitant ADM, and histopathology revealed a 30-mm papillotubular adenocarcinoma extending from the gallbladder body to fundus with invasion into the subserosa. Numerous RAS were present throughout the gallbladder showing various degrees of dysplasia. Ki67 and p53-labeling index (LI) was significantly higher in the dysplastic epithelium compared with normal fundic epithelium. p53-LI was also markedly increased (72.1%) in tissue in front of tumor invasion. Interestingly, these hyperproliferation indicators were extremely high (Ki67-LI: 28.8%; p53-LI: 91.9%) in RAS with low-grade dysplasia even in the gallbladder neck. Although, generally, tumors do not develop in the gallbladder neck with segmental ADM, our results suggest that a gallbladder with ADM has potential for carcinogenesis regardless of location, with segmental ADM. On the basis of histopathology, our patient was diagnosed with GBC arising from RAS with multicentric and multistep growth. A relationship between GBC and ADM, especially segmental ADM, has been suggested but remains controversial. Our experience is very suggestive of carcinogenesis developing from ADM.

Intratumoral lymphangiogenesis of esophageal squamous cell carcinoma and relationship with regulatory factors and prognosis.

The clinical and pathological significance of intratumoral lymphangiogenesis (ITL) with human esophageal squamous cell carcinomas (ESCC) remains unclear, as does the role of signaling molecules such as vascular endothelial growth factor (VEGF)-A,C, platelet-derived growth factor (PDGF)-A, and p53, in the regulation of ITL. Lymphatic vessel density (LVD) was significantly increased in VEGF-A and VEGF-C immunohistochemical score 1 and 2-3 groups as compared to the score 0 group and also with high of VEGF-A, VEGF-C and PDGF-A mRNA expression. Both LVD and blood vessel density (BVD) were significantly greater in the p53 gene mutant group than in the wild-type group. Lymph node metastasis was significantly more frequent with than without ITL and Kaplan-Meier analysis indicated a significantly poorer prognosis. Multivariate analysis using Cox proportional hazard method showed that invasion depth, lymph node metastasis and ITL were independent prognostic factors.

[Educational program in the Medical Science Course, Kitasato University School of Allied Health Sciences].

The aim of education in the Medical Laboratory Science course, Kitasato University School of Allied Health Sciences, is to bring up train students who have Kitasato spirit, for careers in laboratory medicine of hospital or scientific staff of medical companies or as researchers. General and enlightening education concerning "Kitasato spirit" and professional education composed of major subjects was carried out in the first and during the 2nd and two third of 3rd grade, respectively. Medical practice and research training were alternatively carried out for 6 months between November of the 3rd year and November of the 4th year, in order to gain practical experience. Two problem-based learning (PBL) tutorial courses, "Infectious Diseases Course" and "Team Medical Care--Interprofessional Collaborations" were also carried out at the end of the 3rd and beginning of the 4th years, respectively, in order to convert a memory to knowledge. Team medical care course enrolls 1000 students at the School of Allied Health Sciences, Medicine, Nursing, Pharmacy and Kitasato College Applied Clinical Dietetics Course, is now one of special courses available at our university. This attempt is thought to result in a way of thinking that recognizes the importance of co-operation as a team member and personal contributions to actual team medical care.

Lung metastases of a uterine tumor resembling ovarian sex-cord tumor: Report of a rare case.

Uterine tumor resembling an ovarian sex-cord tumor (UTROSCT) is a rare type of uterine neoplasm. We present an extremely rare case of lung metastases from a UTROSCT focusing on the cytologic features. A 69-year-old Japanese woman was admitted to our hospital for further examination and treatment for abnormal shadows in the right lung field. She had a history of total hysterectomy for UTROSCT. Moreover, she underwent wedge resection of the right middle lobe for lung metastasis of UTROSCT in 2011. Enhanced chest computed tomography scan revealed a solid nodule 8 mm in diameter in the right upper lobe and a well-demarcated 33-mm mass or nodule in the lower lobe. Under the diagnosis of metastatic tumors from UTROSCT, she underwent wedge resection of the right upper lobe and segmentectomy of the right S8. Cytologically, the stump smear from the resected tumors revealed round to short spindle-shaped neoplastic small cells arranged in sheets with poor cohesion and no cluster formation. The nuclei were irregular in shape, and the chromatin was finely granular, uniform, and increased. Mitotic figures were not observed. Necrosis was absent in the background. Histologically, the final diagnosis was UTROSCT group II. This is an unusual case of metastatic UTROSCT to the lung in which the cytologic features are described.

Cysteine dioxygenase type 1 (CDO1) gene promoter methylation during the adenoma-carcinoma sequence in colorectal cancer.

BACKGROUND: Progression of colorectal cancer (CRC) has been explained by genomic abnormalities along with the adenoma-carcinoma sequence theory (ACS). The aim of our study is to elucidate whether the promoter DNA methylation of the cancer-specific methylation gene, cysteine dioxygenase 1 (CDO1), contributes to the carcinogenic process in CRC. METHODS: The study group comprised 107 patients with CRC who underwent surgical resection and 90 adenomas treated with endoscopic resection in the Kitasato University Hospital in 2000. We analyzed the extent of methylation in each tissue using quantitative TaqMan methylation-specific PCR for CDO1. RESULTS: The methylation level increased along with the ACS process (p < 0.0001), and statistically significant differences were found between normal-appearing mucosa (NAM) and low-grade adenoma (p < 0.0001), and between low-grade adenoma and high-grade adenoma (p = 0.01), but not between high-grade adenoma and cancer with no liver metastasis. Furthermore, primary CRC cancers with liver metastasis harbored significantly higher methylation of CDO1 than those without liver metastasis (p = 0.02). As a result, the area under the curve by CDO1 promoter methylation was 0.96, 0.80, and 0.67 to discriminate cancer from NAM, low-grade adenoma from NAM, and low-grade adenoma from high-grade adenoma, respectively. CONCLUSIONS: CDO1 methylation accumulates during the ACS process, and consistently contributes to CRC progression.

Histological Risk Factors to Predict Clinical Relapse in Ulcerative Colitis With Endoscopically Normal Mucosa.

BACKGROUND AND AIMS: The current goal of treatment for ulcerative colitis [UC] is endoscopic and ultimately histological mucosal healing. However, there is no consensus on the definition of histological mucosal healing. We evaluated histological risk factors for clinical relapse in UC patients with endoscopically normal mucosa to focus on the importance of histological evaluation. METHODS: Patients with UC who underwent colonoscopy confirming Mayo endoscopic subscore [MES] ≤ 1 with biopsies were enrolled into this retrospective cohort. Three expert pathologists evaluated the presence or absence of chronic inflammatory cell infiltrate, breaches in the surface epithelium, crypt abscesses, mucin depletion, crypt architectural irregularities and basal plasmacytosis. Clinical relapse was defined as partial Mayo score ≥ 3 or modification of induction treatment. Prediction models of clinical relapse were generated, especially in patients with MES 0. RESULTS: A total of 194 UC patients were enrolled. Histological abnormalities existed more frequently in patients with MES 1 than those with MES 0, while the vast majority of patients still possessed at least one abnormality. There was no significant difference in time to relapse between MES 0 and 1. Crypt architectural irregularities and mucin depletion were associated with time to relapse in patients with MES ≤ 1. In patients with MES 0, the presence of mucin depletion was the only factor significantly and independently associated with the risk of relapse (hazard ratio, 2.18 [1.16-5.82]; p = 0.03). CONCLUSIONS: Mucin depletion was shown to be a histological risk factor for clinical relapse in UC patients with MES 0.

Cell cannibalism and nucleus-fragmented cells in voided urine: useful parameters for cytologic diagnosis of low-grade urothelial carcinoma.

OBJECTIVE: To clarify whether the 3 parameters of cell clusters, cell cannibalism and nucleus-fragmented cells could improve diagnostic accuracy for grade 1 urothelial carcinoma (G1UC). STUDY DESIGN: A total of 52 voided urine samples from 31 patients histologically diagnosed as having G1UC were reviewed. In addition, 10 voided urine samples from cases with grade 3 demonstration urothelial carcinoma (G3UC) and 30 voided urine samples from 25 patients with a histologic diagnosis of chronic inflammation of the bladder were evaluated for comparison. Areas of tumor cells with cannibalism were measured. RESULTS: Cell cannibalism was evident in 12 of 31 G1UC cases (38.7%), significantly less often than with G3UC, but never identified in the control group. Mean areas of tumor cells featuring cannibalism were significantly smaller in G1 UC than in G3UC cases. Nucleus-fragmented cells were also less frequent in G1UC than in G3UC, but more common than in the control group. CONCLUSION: Cell cannibalism and nucleus-fragmented cells in voided urine with special attention to areas of tumor cell with cannibalism could be applied as a parameter to improve diagnostic accuracy for G1UC.

Over-the-counter Drug Induced Autoimmune Hepatitis.

A 64-year-old man seeking treatment for a common cold was admitted to our hospital due to symptoms of general fatigue and liver dysfunction. A thorough history review revealed that the patient had recently started taking an over-the-counter (OTC) drug. Drug-induced lymphocyte stimulation tests were positive. Serum markers for autoimmune hepatitis (AIH) were particularly elevated. Liver biopsy revealed spotty necrosis and ceroid-pigmented Kupffer cells and piecemeal necrosis with multiple plasma cells. He responded to corticosteroids, thus suggesting the presence of an immune-mediated component associated with the liver injury. Liver injury after using OTCs should be included in the differential diagnosis for chronic hepatitis with features of AIH.

Spontaneous brain tumor imaging of aged rat by crystal X-ray interferometer-based phase-contrast X-ray CT.

BACKGROUND: Crystal X-ray interferometer-based phase-contrast X-ray computed tomography (C-PCCT) enables the depiction of internal structures of biological tissue without contrast agents. PURPOSE: To determine the advantage of this technique in visualizing detailed morphological structures of a rare spontaneous brain tumor in an aged rat. MATERIAL AND METHODS: An aged rat's spontaneous brain tumor was imaged by C-PCCT without contrast agent. Three-dimensional (3D) images of the tumor microvasculature were reconstructed and compared with pathological pictures. RESULTS: C-PCCT depicted the tumor's various pathological features clearly, e.g. its cell density and vasculature, and blood clots caused by hemorrhaging and/or hematomas. The obtained images resembled pathological pictures with a magnification of ×20 and were used to reconstruct 3D images of the tumor vascularity up to approximately 26 µm in diameter. CONCLUSION: Since C-PCCT is able to depict various pathological conditions, it might be useful for cancer research.

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.