[Effect of adding X-ray examination to endoscopy in the assessment of the invasion depth of early gastric cancer].

In the assessment of invasion depth of early gastric cancer (EGC), the effect of adding X-ray examination to endoscopy was retrospectively investigated in 84 EGC lesions diagnosed at our hospital, including 62 differentiated and 22 undifferentiated lesions. Overall diagnostic accuracy was 75% with endoscopy and 82.1% when X-ray examination was performed in addition to endoscopy. This demonstrated an increase in the accuracy of 7.1% by adding X-ray examination. In terms of presence of ulceration, the additional effect of X-ray examination was higher for lesions without ulceration for both differentiated and undifferentiated lesions. In terms of tumor diameter, the additional effect of X-ray examination was higher for differentiated lesions of ≤30mm and for undifferentiated lesions of ≥21mm. In terms of tumor location, the additional effect of X-ray examination was higher for lesions located in the upper gastric corpus. Depending on the lesion, the addition of X-ray examination to endoscopy contributed to an increase in the accuracy of the assessment of the invasion depth of EGC.

[A case of duodenal neuroendocrine carcinoma composed of small- and large-cell types].

A 78-year-old man underwent a detailed examination by upper gastrointestinal endoscopy for the complaint of epigastric pain. The examination revealed a hemicircumferential type 2 tumor in the descending duodenum. A subsequent biopsy led to a diagnosis of neuroendocrine carcinoma. Subtotal stomach-preserving pancreaticoduodenectomy was performed. The lesion was composed of small- and large-cell neuroendocrine carcinomas. The large-cell type component was positive for both caudal homeobox protein 2 and the cluster of differentiation 138, whereas the small-cell type component was negative for both. Our report may provide valuable information regarding the pathogenesis of neuroendocrine carcinoma.

A case of synchronous quintuple gastric cancer with large-cell endocrine carcinoma.

The patient was a 73-year-old man who visited our department with black stools as the chief complaint. Upper digestive tract endoscopy revealed three type 2 lesions in the lesser curvature of the gastric antrum and the gastric angle and the posterior wall of the upper gastric body, which were diagnosed by biopsy as tub2, por, and sig, respectively. Total gastrectomy was performed. The final pathological diagnosis was quintuple gastric cancer with a main lesion of large-cell endocrine carcinoma and four adenocarcinoma sublesions. We report this extremely rare case of gastric endocrine cell carcinoma complicated by adenocarcinoma.

Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency.

Evaluation of parameters relating to serum ferritin and iron is critically important in the diagnosis of iron deficiency anemia (IDA). The recent development of automated systems for hematology analysis has made it possible to measure reticulocyte hemoglobin equivalent (RET-He), which is thought to reflect iron content in reticulocytes, in the same sample used for complete blood count tests. If RET-He is, indeed, capable of evaluating iron deficiency (ID), it would be useful for immediate diagnosis of IDA. In the present study, we examined the usefulness of RET-He for diagnosis of ID. Blood samples were obtained from 211 patients. Anemia was defined as hemoglobin (Hb) level of <12 g/dL. Iron deficiency was defined as serum ferritin level of <12 ng/mL. Patients were classified into four groups: IDA, ID, control, and non-ID with anemia. Patients in the IDA group had significantly lower RET-He levels than those in the control group. RET-He correlated with serum ferritin in the IDA and ID groups. The area under the curve for RET-He was 0.902, indicating that RET-He facilitates the diagnosis of ID with high accuracy. RET-He changed in parallel with changes in Hb during iron administration for 21 IDA patients. Our results indicate that RET-He may be a clinically useful marker for determining ID in the general population.

A case of mixed adenoneuroendocrine carcinoma of the stomach.

A 71-year-old man who tested positive in a pepsinogen test also underwent upper gastrointestinal endoscopy. A 0-IIc lesion was identified at the posterior wall of the antrum. Biopsy findings indicated endocrine cell carcinoma. The patient underwent distal gastrectomy, and subsequent histopathological examination of the resected specimens showed a moderately differentiated adenocarcinoma (tub2) in the mucosa with transformation to small cell carcinoma in the submucosal and muscle layers. The final diagnosis was of a mixed adenoneuroendocrine carcinoma. We herein describe a case report of this patient with this rare form of gastric carcinoma.

[A case of large cell neuroendocrine carcinoma of the rectum].

A 77-year-old woman was referred to our hospital because of blood in feces and anal pain. Colonoscopy revealed a villous semicircular tumor in the rectum. A biopsy showed well-differentiated adenocarcinoma. Miles' operation was performed because of the persistence of anal pain and blood in feces. Histological and immunohistochemical analysis showed coexistent tubulovillous adenoma, tubulovillous adenocarcinoma, and large cell neuroendocrine carcinoma (LCNEC), which was positive for CD56, chromogranin A, and synaptophysin. Pathological examination revealed that most of the lesion was occupied by the LCNEC. The tumor was therefore diagnosed as LCNEC of the rectum. The patient underwent adjuvant chemotherapy with cisplatin (CDDP), irinotecan (CPT-11), and mFOLFOX6, but died because of LCNEC progression 10 months after the operation. LCNEC rarely occurs in the gastrointestinal tract; here we report a case of rectal LCNEC.

An invasive extragastrointestinal stromal tumor curably resected following imatinib treatment.

Extragastrointestinal stromal tumors (EGISTs) are rare tumors located outside the gastrointestinal tract. While curable resection is accepted as a noninvasive EGIST treatment, the therapeutic strategy for invasive EGISTs has not yet been established. The present report is the first to show a case of invasive EGIST completely resected after downsizing the tumor with imatinib treatment. A 69-year-old female had multiple masses adjacent to the stomach and ileocecum. The primary lesion measured 18 cm in size and had invaded the stomach, pancreas and liver. The histological findings of fine-needle aspiration samples revealed a proliferation of dysplastic spindle cells that exhibited immunoreactivity for anti-c-kit antibodies. The masses were therefore diagnosed as multiple GISTs with invasion to other organs, with origin difficult to determine at the time. Nineteen months after the imatinib treatment, the tumors were downsized and distinct from the stomach, pancreas and liver. Accordingly, the tumors were regarded to be EGISTs derived from the mesentery. Because they slightly regressed 26 months after treatment, surgery was applied to remove the EGISTs. The intraoperative findings showed no invasive signs, and the tumors were completely removed. The histological findings revealed the presence of dysplastic and c-kit-positive spindle cells in the tumor with an MIB-I index of more than 5%, resulting in a final diagnosis of high-risk EGIST derived from the mesentery. No recurrence was detected for 16 months after resection. In conclusion, preoperative treatment with imatinib followed by curable resection is a feasible option to cure invasive EGISTs.

Hepcidin is down-regulated in alcohol loading.

BACKGROUND: It is common for alcoholic patients to have excess iron accumulation in the liver, which may contribute to the development of alcoholic liver disease (ALD). However, the mechanism of hepatic iron uptake in ALD is still obscure. Recently, a novel iron-regulatory hormone hepcidin was found that suppresses the absorption of iron from the small intestine and the release of iron from macrophages. To elucidate the contribution of hepcidin toward the hepatic excess iron accumulation in ALD, we examined whether alcohol loading affects hepcidin expression both in ALD patients and in an ethanol-fed mouse model. METHODS: Serum prohepcidin concentration was quantified by enzyme-linked immunosorbent assay. Hepatic hepcidin-1 and hepcidin-2 mRNA expressions in mouse liver were evaluated by quantitative real-time reverse-transcriptase polymerase chain reaction method. The protein expression of prohepcidin in mouse liver was examined immunohistochemically by rabbit antimouse prohepcidin antibody. RESULTS: Serum prohepcidin concentration in ALD was significantly lower than that in healthy subjects (p<0.001). Especially, serum prohepcidin concentrations were decreased in the patients whose serum ferritin value was high. In the ethanol-fed mouse model, hepatic hepcidin-1 mRNA expression was significantly lower than that in control (p=0.04). Prohepcidin was expressed in the cytoplasm of hepatocytes of mice liver tissue sections, and its expression was decreased after ethanol loading. CONCLUSION: Alcohol loading down-regulates hepatic hepcidin expression and leads to the increase of iron absorption from the intestine.

Up-regulation of ADRP in fatty liver in human and liver steatosis in mice fed with high fat diet.

The present study was performed to examine a role of adipose differentiation-related protein (ADRP) in the process of liver steatosis. Immunohistochemical findings indicated that ADRP expression is increased in the hepatocytes in patients with fatty liver when compared with normal liver. ADRP expression is localized in the surface of lipid droplets in the hepatocytes. Increased expression of ADRP mRNA and protein was similarly observed in fatty liver in ob/ob mice and the liver steatosis induced by high fat diet in mice. The up-regulation of ADRP mRNA and protein in the liver by high fat diet was identified in the surface of lipid droplets in a time-dependent manner. Recent studies demonstrated that up-regulation of PPARgamma in the hepatocytes is deeply involved in liver steatosis. To clarify whether ADRP expression is increased by PPARgamma activation in hepatocytes, we examined the effect of a PPARgamma ligand, troglitazone, on ADRP mRNA expression in HepG2 cells. ADRP mRNA expression was increased by troglitazone in dose- and time-dependent manners. All these results suggest that ADRP is up-regulated in liver steatosis in human and mice, and that high fat diet increases expression of ADRP through PPARgamma activation, followed by induction of liver steatosis.

Increased expression of PPARgamma in high fat diet-induced liver steatosis in mice.

The present study was performed to examine a hypothesis that peroxisome proliferator-activated receptor gamma (PPARgamma) is implicated in high fat diet-induced liver steatosis. Mice were fed with control or high fat diet containing approximately 10% or 80% cholesterol, respectively. Macroscopic and microscopic findings demonstrated that lipid accumulation in the liver was observed as early as 2 weeks after high fat diet and that high fat diet for 12 weeks developed a fatty liver phenotype, establishing a novel model of diet-induced liver steatosis. Gene profiling with microarray and real-time PCR studies demonstrated that among genes involved in lipid metabolism, adipogenesis-related genes, PPARgamma and its targeted gene, CD36 mRNA expression was specifically up-regulated in the liver by high fat diet for 2 weeks. Immunohistochemical study revealed that PPARgamma protein expression is increased in the nuclei of hepatocytes by high fat diet. It was also shown that protein expression of cAMP response element-binding protein (CREB), an upstream molecule of PPARgamma, in the liver was drastically suppressed by high fat diet. All these results suggest for the first time that the CREB-PPARgamma signaling pathway may be involved in the high fat diet-induced liver steatosis.

Usefulness of recombinant Em18-ELISA to evaluate efficacy of treatment in patients with alveolar echinococcosis.

Alveolar echinococcosis (AE) is a rare parasitic disease caused by Echinococcus multicularis and most commonly involves the liver. Early diagnosis is essential to improve the prognosis of patients with AE of the liver. Em18, an 18-kD diagnostic antigen from Echinococcus multilocularis, is highly specific and sensitive to detect AE. We previously reported that an enzyme-linked immunosorbent assay (ELISA) system using a recombinant Em18 antigen (RecEm18) was highly useful in the differential serodiagnosis of AE. In this report, we present seven AE patients who showed dynamic changes in RecEm18-ELISA values in the course of long-term follow up of albendazole (ABZ) chemotherapy, and/or resections of the liver or bone metastasis. All seven AE patients revealed positive values, over the cutoff level, of the RecEm18-ELISA before the treatments. The values in six patients fell below the cutoff level after the treatments, but the value in a patient with recurrence never fell below the cutoff level, and increased again. From these results, it seems that the RecEm18-ELISA is useful to evaluate the efficacy of treatment and predict recurrence in patients with AE. RecEm18-ELISA may be an important examination for: (a) the mass screening of AE in Japan, (b) the confirmative diagnosis of AE prior to surgical and/or chemotherapeutic treatments, (c) the follow up of AE patients after treatments, and (d) for deciding on the discontinuation of chemotherapy in patients with an appropriate response.

Usefulness of contrast-enhanced wide-band Doppler ultrasonograpy to diagnose alveolar echinococcosis of the liver and evaluate the effect of the treatment.

Alveolar echinococcosis is a rare parasitic disease caused by Echinococcus multicularis and most commonly involves the liver. Early diagnosis and accurate evaluation of the effect of the treatment are essential to improve the prognosis of patients with alveolar echinococcosis of the liver (AEL). The aim of this study was to demonstrate the characteristic imaging of AEL by contrast-enhanced Dynamic Flow (CE-DF) employing a wide-band Doppler technique for the diagnosis and the accurate evaluation of the effect of the treatment. Four patients with five AEL lesions before treatment or during medication were examined by CE-DF. All of the five AEL lesions examined by CE-DF revealed a defect with an irregular and distinct margin like a worm-eaten defect appearance, which was never observed on other hepatic lesions, in liver perfusion image during post-vascular phase. In addition, CE-DF made it possible to measure the size of AEL lesions accurately because the margin was detected distinctly. These data suggest that CE-DF is clinically useful for the diagnosis of AEL and the evaluation of the effect of the treatment.