Hepatocellular Carcinoma in a Patient with Hereditary Hemorrhagic Telangiectasia.

A 76-year-old woman with hereditary hemorrhagic telangiectasia (HHT) showed elevated serum hepatobiliary enzyme levels, and abdominal imaging studies revealed a hepatic tumor. Her serum alpha-fetoprotein level was 759.5 ng/mL. A pathological examination after hepatectomy confirmed a diagnosis of hepatocellular carcinoma (HCC). An examination of the surrounding liver revealed dilated vessels and thickened endothelial cells without inflammations. HHT patients without other risk factors (like this patient) reportedly have a lower incidence of common cancers, including HCC, in comparison to the unaffected population. One intriguing hypothesis that might explain the hepatocarcinogenesis in this situation is the ischemic liver cirrhosis theory, which suggests that chronic ischemia may cause parenchymal strain and promote inappropriate hepatocyte proliferation.

The Interrelationship between Abscisic Acid and Reactive Oxygen Species Plays a Key Role in Barley Seed Dormancy and Germination.

Seed dormancy is one of the adaptive responses in the plant life cycle and an important agronomic trait. Reactive oxygen species (ROS) release seed dormancy and promote seed germination in several cereal crops; however, the key regulatory mechanism of ROS-mediated seed dormancy and germination remains controversial. Here, we focused on the relationship between hydrogen peroxide (a ROS) and abscisic acid (ABA) in dormant and non-dormant barley seeds. The hydrogen peroxide (H2O2) level produced in barley seed embryos after imbibition was higher in non-dormant seeds than in dormant seeds. H2O2 regulated the ABA content in the embryos through ABA-8'-hydroxylase, an ABA catabolic enzyme. Moreover, compared with non-dormant seeds, in dormant seeds the activity of NADPH oxidase, which produces ROS, was lower, whereas the activity of catalase, which is a H2O2 scavenging enzyme, was higher, as was the expression of HvCAT2. Furthermore, precocious germination of isolated immature embryos was suppressed by the transient introduction of HvCAT2 driven by the maize (Zea mays) ubiquitin promoter. HvCAT2 expression was regulated through an ABA-responsive transcription factor (HvABI5) induced by ABA. These results suggest that the changing of balance between ABA and ROS is active in barley seed embryos after imbibition and regulates barley seed dormancy and germination.

Role of reactive oxygen species produced by NADPH oxidase in gibberellin biosynthesis during barley seed germination.

NADPH oxidase catalyzes the production of the superoxide anion (O2(-)), a reactive oxygen species (ROS), and regulates the germination of barley (Hordeum vulgare L.). Diphenyleneiodonium (DPI) chloride, an NADPH oxidase inhibitor, delayed barley germination, and exogenous H2O2 (an ROS) partially rescued it. Six enzymes, ent-copalyl diphosphate synthase (CPS), ent-kaurene synthase (KS), ent-kaurene oxidase (KO), ent-kaurenoic acid oxidase (KAO), GA20-oxidase (GA20ox) and GA3-oxidase (GA3ox), catalyze the transformation of trans-geranylgeranyl diphosphate to active gibberellin, which promotes germination. Exogenous H2O2 promoted the expressions of HvKAO1 and HvGA3ox1 in barley embryos. These results suggest that ROS produced by NADPH oxidase are involved in gibberellin biosynthesis through the regulation of HvKAO1 and HvGA3ox1.

A Role for Reactive Oxygen Species Produced by NADPH Oxidases in the Embryo and Aleurone Cells in Barley Seed Germination.

Reactive oxygen species (ROS) promote the germination of several seeds, and antioxidants suppress it. However, questions remain regarding the role and production mechanism of ROS in seed germination. Here, we focused on NADPH oxidases, which produce ROS. After imbibition, NADPH oxidase mRNAs were expressed in the embryo and in aleurone cells of barley seed; these expression sites were consistent with the sites of ROS production in the seed after imbibition. To clarify the role of NADPH oxidases in barley seed germination, we examined gibberellic acid (GA) / abscisic acid (ABA) metabolism and signaling in barley seeds treated with diphenylene iodonium chloride (DPI), an NADPH oxidase inhibitor. DPI significantly suppressed germination, and suppressed GA biosynthesis and ABA catabolism in embryos. GA, but not ABA, induced NADPH oxidase activity in aleurone cells. Additionally, DPI suppressed the early induction of α-amylase by GA in aleurone cells. These results suggest that ROS produced by NADPH oxidases promote GA biosynthesis in embryos, that GA induces and activates NADPH oxidases in aleurone cells, and that ROS produced by NADPH oxidases induce α-amylase in aleurone cells. We conclude that the ROS generated by NADPH oxidases regulate barley seed germination through GA / ABA metabolism and signaling in embryo and aleurone cells.

Programmed cell death in barley aleurone cells is not directly stimulated by reactive oxygen species produced in response to gibberellin.

The cereal aleurone layer is a secretory tissue that produces enzymes to hydrolyze the starchy endosperm during germination. We recently demonstrated that reactive oxygen species (ROS), produced in response to gibberellins (GA), promoted GAMyb expression, which induces α-amylase expression in barley aleurone cells. On the other hand, ROS levels increase during programmed cell death (PCD) in barley aleurone cells, and GAMyb is involved in PCD of these cells. In this study, we investigated whether the ROS produced in response to GA regulate PCD directly by using mutants of Slender1 (SLN1), a DELLA protein that negatively regulates GA signaling. The wild-type, the sln1c mutant (which exhibits gibberellin-type signaling even in the absence of GA), and the Sln1d mutant (which is gibberellin-insensitive with respect to α-amylase production) all produced ROS in response to GA, suggesting that ROS production in aleurone cells in response to GA is independent of GA signaling through this DELLA protein. Exogenous GA promoted PCD in the wild-type. PCD in sln1c was induced even without exogenous GA (and so without induction of ROS), whereas PCD in Sln1d was not induced in the presence of exogenous GA, even though the ROS content increased significantly in response to GA. These results suggest that PCD in barley aleurone cells is not directly stimulated by ROS produced in response to GA but is regulated by GA signaling through DELLA protein.

Oxaliplatin-induced liver injury mimicking metastatic tumor on images: a case report.

Oxaliplatin-based chemotherapy is widely used for advanced colorectal cancer treatment, but it occasionally induces liver injury that is characterized histologically by sinusoidal dilatation, hepatic plate atrophy and/or venular obstruction. Most of the patients do not reveal apparent radiological abnormalities, however. Here, we report the case of a 47-year-old man with a radiologically detectable mass-forming oxaliplatin-induced sinusoidal injury that mimicked multiple liver tumors. These mass lesions were found on computed tomography images after the administration of six cycles of folinic acid, fluorouracil and oxaliplatin therapy as adjuvant chemotherapy for Stage III rectal cancer. The patient had to undergo liver resection because imaging studies could not exclude metastases. The histological examination revealed that a resected mass lesion was composed of severe sinusoidal dilatation. Milder dilatation was also seen in the surrounding parenchyma. We diagnosed the patient as having an oxaliplatin-induced sinusoidal injury with severe deviation. As oxaliplatin is a standard agent in colorectal cancer therapy today, all clinicians and pathologists should be aware of such non-neoplastic lesions as one of the rare differential diagnoses of metastatic liver tumor, to prevent overtreatment.

[A case of advanced hepatocellular carcinoma with portal vein invasion successfully treated by sorafenib].

A 73-year-old man was followed up for HCV-associated chronic hepatitis and hepatocellular carcinoma (HCC), developed in segment 8 of the liver. Radiofrequency ablation (P-RFA) was used to treat the tumor in June 2004. Afterwards, the patient underwent repetitive transcatheter arterial chemoembolization (TACE) against recurrent tumors 5 times. An abdominal computed tomogram (CT) showed an infiltrative mass in the left liver with tumor thrombus invading into the umbilical portion. Transarterial infusion (TAI) therapy of cisplatin (CDDP) was performed 2 times, in January and June of 2010. The size of the main tumor was decreased according to CT, and tumor marker levels such as AFP and PIVKA-II also decreased, but tumor thrombus of the portal vein developed into the main trunk (Vp4). We started therapy with sorafenib in July, 2010. Two months later, an abdominal CT revelaed further reduction of the main tumor and a shrunken tumor thrombus of the portal vein back to the left lobe. The therapeutic effect of sorafenib against HCC with tumor thrombus of the portal vein continued for 9 months.

[A case of drug-induced eosinophilic pneumonia due to tegafur-uracil(UFT®)].

A 68-year-old female received a left lower lobectomy for lung cancer (adenocarcinoma, pT2N1M0, stage II B). She had a postoperative bronchial fistula that was treated conservatively and cured. Two months after the operation, tegafur-uracil (UFT) 300 mg/day was initiated.She felt dyspnea on exertion after taking UFT for two weeks, and some infiltration shadows were observed on a chest X-ray two weeks later. A chest CT scan revealed unsegmental infiltration shadows at the intermediate areas of the right middle and lower lobes, and an air-bronchogram was observed inside of the shadows. A bronchoscopy was performed. Bronchoalveolar lavage revealed a high fraction rate of eosinophil(24%), and a transbronchial lung biopsy revealed infiltrations of lymphocytes, eosinophils and neutrophils into the intra-alveolar space. However, fibrosis of the alveolar wall was not observed. A drug-induced lymphocyte stimulation test was performed for UFT, resulting positive. She was diagnosed as drug-induced eosinopilic pneumonia due to UFT. After she discontinued UFT and started 30 mg/day of prednisolone, dyspnea and infiltrations on chest X-ray disappeared.

[Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma accompanied with cystic change].

A 64-year-old male with throat discomfort visited our hospital, and a chest computed tomography (CT) scan revealed a cystic lesion with a central solid component in the right lung (in the lower lobe, 4.1 x 3.9 cm in diameter). Transbronchial lung biopsy was performed and the lesion was diagnosed as mucosa-associated lymphoid tissue (MALT) lymphoma of the lung. No other lymphoma lesion was detected and it was diagnosed as the stage I-E, and a right lower lobectomy was performed. The cystic lesion derived from alveolus and bronchus destroyed by lymphoma infiltration and it might be caused by air retention due to check-valve mechanism.

Evaluation of cholecystic venous flow using indocyanine green fluorescence angiography.

BACKGROUND/PURPOSE: The cholecystic veins are thought to be an important metastatic route of gallbladder carcinoma to the liver. In the present study we evaluated the cholecystic venous drainage area, utilizing a novel method, indocyanine green (ICG) fluorescence angiography after superselective catheterization of the cholecystic artery, to detect and elucidate cholecystic venous flow. METHODS: Cannulation of the cholecystic artery was performed under laparotomy in nine patients who required a cholecystectomy. After ICG injection into the cholecystic artery, the cholecystic venous flow images were visualized with a near-infrared camera system and were analyzed according to site, shape, and time of fluorescence. RESULTS: Fluorescence images of the cholecystic venous flow could be viewed as real-time images in all patients. We demonstrated that the route of the cholecystic venous flow could be classified into two patterns: type 1, in which the cholecystic veins flowed directly into the hepatic parenchyma adjacent to the gallbladder; and type 2, in which the veins flowed into sites separate from the gallbladder. In the type 1 pattern, fluorescence was observed in segment (S; defined according to Couinaud's nomenclature) 4a or S5 adjacent to the gallbladder in all cases. On the other hand, in the type-2 pattern, fluorescence was observed in S4a (6/9), S5 (8/9), S4b (2/9), S3 (2/9), S1 (1/9), S2 (1/9), and S8 (1/9) distant from the gallbladder. Overall, two-thirds of the cases showed fluorescence in segments other than S4a or S5. CONCLUSIONS: Indocyanine green (ICG) fluorescence angiography is considered to be a useful method to detect and elucidate cholecystic venous flow in real time. This study showed that the cholecystic venous flow spread to the liver through two different pathways, one that flowed directly into the hepatic parenchyma adjacent to the gallbladder, while the other flowed into sites separate from the gallbladder. Taking these findings into consideration, we may therefore need to reconsider the preventive effects of a hepatic resection.

Nonfunctioning endocrine pancreatic tumor examined with 18F-FDG PET/CT.

A 71-year-old woman with type 2 diabetes mellitus complained of generalized fatigue. A 36-mm tumor in the pancreatic tail was detected with ultrasonography. The tumor was found to have marked hypervascularity with contrast-enhanced computed tomography (CT) and magnetic resonance. Combined (18)F-fluorodeoxyglucose positron emission tomography and CT ((18)F-FDG PET/CT) showed (18)F-FDG by the tumor with a maximal standardized uptake value of 2.98 at 50 min and 3.29 at 100 min following injection of (18)F-FDG. (18)F-FDG PET/CT suggested no extrapancreatic spread of the tumor. The patient had no pancreatic hormone-associated symptoms. Distal pancreatectomy was performed, and a well-differentiated endocrine tumor was diagnosed. The resected specimen showed neither infiltration of adjacent structures nor metastasis to regional lymph nodes. The present case suggests that (18)F-FDG PET/CT is a reliable modality for staging endocrine pancreatic tumors.

[A case of dihydropyrimidine dehydrogenase (DPD) deficiency with severe side effects from UFT/Uzel administration].

5-FU is among the drugs most frequently used in the treatment of gastrointestinal malignancies. Also, it has been reported to reveal severe side effects in the case of a dihydropyrimidine dehydrogenase (DPD) deficiency. A 75-year-old man showed severe nausea and vomiting after administration of UFT/Uzel as adjuvant chemotherapy. Because of severe thrombocytopenia and grade 4 neutropenia, platelet transfusion and G-CSF administration were performed. With time, the leukocyte, neutrophil and platelet count recovered to normal level. We strongly suspected a DPD deficiency from the result of urinary pyrimidine analysis.

Pyogenic liver abscess after choledochoduodenostomy for biliary obstruction caused by autoimmune pancreatitis.

A 68-year-old man underwent cholecystectomy and choledochoduodenostomy for biliary obstruction and nephrectomy for a renal tumor. Based on clinical and histopathologic findings, autoimmune pancreatitis (AIP) was diagnosed. The renal tumor was diagnosed as a renal cell cancer. Steroid therapy was started and thereafter pancreatic inflammation improved. Five years after surgery, the patient was readmitted because of pyrexia in a preshock state. A Klebsiella pneumoniae liver abscess complicated by sepsis was diagnosed. The patient recovered with percutaneous abscess drainage and administration of intravenous antibiotics. Liver abscess recurred 1 mo later but was successfully treated with antibiotics. There has been little information on long-term outcomes of patients with AIP treated with surgery. To our knowledge, this is the second case of liver abscess after surgical treatment of AIP.