Kozo Ujike

Improvement of serum amino acid profile in hepatic failure with the bioartificial liver using multicellular hepatocyte spheroids

We designed a bioartificial liver support system in which encapsulated multicellular spheroids of rat hepatocytes were utilized as a bioreactor in a hollow fiber cartridge. The spheroids, formed in a positively charged polystyrene dish that contained hormonally defined medium, were encapsulated into microdroplets of agarose that contained about 9 × 107 rat hepatocytes. The medium, including 150 mL reservoir volume, was circulated in a closed circuit in which the cartridge was inserted. The pH and levels of dissolved oxygen were monitored and automatically regulated so that they were maintained within a constant range for 72 h. Albumin accumulated in the circuit at the rate of 2.0 mg/L/h in this system. When the bioreactor cells in the system were replaced with Hep G2 cells, a human hepatoblastoma cell line, albumin accumulated at the rate of 0.15 mg/L/h. The spheroids of primary culture hepatocytes had 13 times higher albumin‐producing capacity than the aggregates of Hep G2. The serum of a patient with fulminant hepatic failure was circulated in this system with the spheroids of primary culture hepatocytes. The concentration of branched amino acid (BCAA) in the circuit significantly increased during the 48 h circulation, while the concentration of aromatic amino acid (AAA) and methionine decreased. The ratio of BCAA/AAA increased from 0.640 to 0.772, indicating that the hepatocyte spheroids had improved the imbalance of the amino acid profile in the serum. These findings indicate that this system may be a useful model for an artificial liver support.

Unusual variant of left paraduodenal hernia herniated into the mesocolic fossa leading to jejunal strangulation

Abstract: Paraduodenal hernia is a rare condition in which the small bowel loops are herniated into an unusual fossa in the periduodenal area. We treated a patient with paraduodenal hernia diagnosed pre-operatively. A 28-year-old woman was admitted to our hospital because of intermittent abdominal pain. Abdominal ultrasonography revealed a large tumor adjacent to the pancreas. Provisional diagnosis made according to computed tomography (CT) findings was tumor of the pancreas tail. However, on a CT scan performed after the administration of diatrizoate meglumine/diatrizoate sodium (Gastrografin, Schering, Berlin, Germany) the mass was shown as a jejunum loop located between the stomach and the pancreas body. Subsequent laparotomy revealed that the jejunum loop was herniated into an unusually large mesocolic fossa and that the hernial orifice was covered by the adhesion between the transverse and descending colons. It seemed that the small intestine within the mesocolic fossa was strangulated by this adhesion. The patients abdominal pain resolved postoperatively. These observations suggest that paraduodenal hernia should be suspected in patients with chronic, atypical abdominal pain, regardless of the findings for small bowel obstruction.

Mixed connective tissue disease associated with idiopathic portal hypertension and chronic thyroiditis

We report a patient with mixed connective tissue disease (MCTD) associated with idiopathic portal hypertension (IPH) and chronic thyroiditis. The patient was a 68-year-old Japanese woman who was admitted to our hospital for treatment of bleeding esophageal varices. She had previously exhibited Raynauds phenomenon and had had arthritis for about 30 years. She also had had high titers anti-U1 of ribonucleoprotein (RNP) anti-single strand-DNA autoantibodies for 2 years, and had been diagnosed with MCTD 1 year previously. The bleeding from esophageal varices was successfully stopped by endoscopic injection sclerotherapy. Results of laboratory examinations, imaging examinations, and laparoscopy, including liver biopsy, indicated that the esophageal varices were caused by portal hypertension due to IPH. The patient also had a diffusely firm and enlarged goiter and hypothyroidism, and she exhibited anti-thyroid microsomal antibodies and anti-thyroglobulin antibodies, she was diagnosed as having a complication of chronic thyroiditis. This association of MCTD, IPH, and chronic thyroiditis is quite rare and provides a unique opportunity to observe immunological involvement in the pathogenesis of IPH.

Diagnostic Accuracy of Laparoscopic Liver Biopsy in Chronic Liver Diseases, Comparison of Laparoscopic and US‐Guided Liver Biopsy Results

Liver biopsies were carried out using three different needles, a Vim‐Silverman needle 2.5 mm in outer caliber, an 18‐Gauge (18G) Majima needle, and a 17‐Gauge (17G) Majima needle. The biopsies were obtained from nearby locations on the liver surface under laparoscopic observation, to ascertain differences in histological diagnosis according to the size of the biopsy specimen. The biopsy specimens obtained with the Vim‐Silverman needle were wider than those obtained with the other two needles. The agreement in histological diagnoses of the liver, obtained with the Vim‐Silverman needle versus the 18G Majima needle, was 26.0%, while that between the Vim‐Silverman needle and the 17G Majima needle was 40.0%. Histological diagnosis tended to be underestimated in small biopsy specimens in advanced chronic liver diseases. A questionnaire survey, conducted in 92 hospitals affiliated with Okayama University Medical School, revealed US‐guided liver biopsy to be the practice of choice in 57 of 92 (62.0%) hospitals, and 18G needles were used in US‐guided liver biopsy in 35 of 78 (45.2%) hospitals.

Transient appearance of perisinusoidal chondroitin sulfate proteoglycans associated with enhanced expression of biglycan gene during d-galactosamine-induced acute liver injury in rats

Abstract The present study investigated the chondroitin sulfate proteoglycan changes in the liver during acute liver injury induced by a one-shot administration of d -galactosamine in rats. Chondroitin sulfate proteoglycans were immunohistochemically stained with monoclonal antibodies, 1B5, 2B6, and 3B3, which recognize different stub structures of chondroitin sulfate chain exposed after treatment with chondroitinase ABC. The presence of biglycan, a dermatan sulfate/chondroitin sulfate proteoglycan, in the chondroitin sulfate proteoglycans was examined by determining the expression of biglycan gene by PCR and RNase protection assay. Immunoreactive chondroitin sulfate proteoglycans were detected in the ECM of portal areas and along the sinusoid, in either a radial or scattered dot pattern, out from the portal area. The positive signals in the portal area were detected in both control and injured rats. However, those along the sinusoid were detected only in injured rats, transiently from day 1 to 4 after the administration of d -galactosamine. The expression of biglycan gene was detected in both control and injured rats, and was four-five-fold the basal level at day 1 to 2 in the injured rats. These results suggest that the appearance of chondroitin sulfate proteoglycan along liver sinusoid is specific to acute liver injury, and biglycan is partially involved.

Amyloid Colitis: Successful Treatment with Colchicine Therapy

Abstract: We treated a case of systemic amyloidosis which exhibited clinical symptoms of amyloid colitis. The patient was a 61‐year‐old man with bloody diarrhea. Endoscopic examination revealed multiple erosions and small ulcerations with bleeding, bloodshot mucosa and loss of the normal vascular pattern in the transverse colon. Histological examination revealed infiltration by inflammatory cells in the lamina propria, and congo red dye showed deposition of amyloid material in the submucosa and in the walls of blood vessels. Endoscopic examination of the upper digestive tract revealed an erosive reddish area in the antrum, and a biopsy specimen from this lesion showed amyloid material histologically. With ultrasonic cardiography, amyloid deposition was suspected in the heart. Therefore, the patient was diagnosed with systemic amyloidosis. We started the administration of colchicine 1 mg/day and commenced follow‐up endoscopy. The patients diarrhea was improved after the administration of colchicine, and mucosal lesions of the transverse colon were improved endoscopically. Moreover, amyloid deposition in the cardiac wall seemed to have disappeared on ultrasonic cardiography. From these observations, colchicine therapy was considered to be an effective treatment for systemic amyloidosis in the present case.

A Case of Melanosis Duodeni Alleviated by the Discontinuation of Ferrous Sulfite

Abstract: A case of melanosis duodeni is presented. The patient was an 80‐year‐old Japanese woman who had received oral ferrous sulfite for 19 months. Endoscopic examination of the duodenum showed marked pigmentation of the duodenal mucosa. Histological and electron microscopic examinations revealed that the pigment had histochemical features compatible with hemosiderin and was located mainly within macrophage lysosomes in the lamina propria. We discontinued the administration of ferrous sulfite and commenced follow‐up endoscopy. The pigmentation disappeared within 7 months of discontinuing treatment. Thus, the ferrous sulfite was speculated to be the causative agent of the pigmentation in the present case. The patient had concomitant hypertension, rheumatoid arthritis, anemia and chronic renal failure. The possible associations of these complications with the development of duodenal pigmentation were also considered.