Case of primary hepatic gastrinoma: Diagnostic usefulness of the selective arterial calcium injection test

Gastrinomas mainly occur in the duodenum and pancreas. Primary hepatic gastrinoma is rare and difficult to diagnose because the liver is a frequent site of metastatic gastrinomas. Clinical factors were assessed in a 28‐year‐old man with diarrhea and heartburn who was hospitalized for recurrent duodenal ulcers. Abdominal ultrasound, endoscopic ultrasound and computed tomography (CT) could not detect a tumor in the duodenum or pancreas. His gastrin level was 846 pg/mL and magnetic resonance imaging showed a mass 12 mm in diameter in the right robe of the liver. A selective intra‐arterial calcium injection (SACI) test and 68‐gallium edotreotide positron emission tomography CT (Ga‐DOTATOC PET‐CT) were therefore performed. Calcium gluconate injection into the proper hepatic artery resulted in a marked increase in serum gastrin concentration in the right hepatic vein, with Ga‐DOTATOC PET‐CT showing uptake only by the liver mass. Following a diagnosis of primary hepatic gastrinoma, the tumor was resected. A histopathological examination indicated gastrinoma. Six months postoperatively, he has no symptoms, is not taking proton‐pump inhibitors and his gastrin level remains within the normal range. The SACI test and the clinical course of this patient strongly suggest that the tumor was a primary hepatic gastrinoma. The SACI test is helpful in the diagnosis of primary hepatic gastrinoma.     

Case of ketoacidosis by a sodium‐glucose cotransporter 2 inhibitor in a diabetic patient with a low‐carbohydrate diet

We present a case of a 32‐year‐old diabetic woman with Prader–Willi syndrome who developed severe ketoacidosis caused by a sodium‐glucose cotransporter 2 (SGLT2) inhibitor, a novel class of antihyperglycemic agents, during a strict low‐carbohydrate diet. At admission, a serum glucose level of 191 mg/dL was relatively low, though laboratory evaluations showed severe ketoacidosis. This is the first report of ketoacidosis caused by a SGLT2 inhibitor. It is necessary to not only pay attention when using a SGLT2 inhibitor in patients following a low‐carbohydrate diet, but also to start a low‐carbohydrate diet in patients treated with a SGLT2 inhibitor because of a high risk for developing ketoacidosis.     

Knowledge, attitudes, and practices of Japanese travelers towards malaria prevention during overseas travel

BACKGROUND: There has been some concern that Japanese travelers are not adequately protected against malaria, especially when compared to Western travelers. Multi-national studies of knowledge, attitudes, and practices (KAP) regarding malaria risk have previously been conducted in travelers. METHODS: We conducted a KAP study in Japanese travelers using the same standardized questionnaire as the previous studies. Unlike those studies, questionnaires could not be distributed at departure lounges/gates at international airports, and therefore, travelers were sourced from several different study sites, targeting different populations. RESULTS: A total of 212 Japanese travelers who had visited malarious areas were enrolled, of which 63.2% had visited Asia and 28.3% visited sub-Saharan Africa. Significant shortcomings in KAP were noted with respect to lack of knowledge about symptoms of malaria, poor awareness of malaria risk at their destination, and non-adherence to adequate antimosquito measures. Chemoprophylaxis use was lower among Japanese travelers than travelers from other countries, even when confining to those traveling to sub-Saharan Africa. CONCLUSIONS: Japanese travel medicine providers and general practitioners who engage in pre-travel consultation should raise awareness of travelers about the seriousness of malaria, the need for improved compliance with chemoprophylaxis, and the importance of being properly prepared prior to departure.     

Significance of plasma 7alpha-hydroxy-4-cholesten-3-one and 27-hydroxycholesterol concentrations as markers for hepatic bile acid synthesis in cholesterol-fed rabbits

Plasma 7alpha-hydroxy-4-cholesten-3-one has been used as an index of hepatic bile acid synthesis. The aim of the current study was to ascertain whether the level of this oxysterol reflects hepatic cholesterol 7alpha-hydroxylase activity when plasma cholesterol concentrations are markedly changed. In addition, the relationship of hepatic sterol 27-hydroxylase activity with plasma concentrations of 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid was studied. We used New Zealand white rabbits fed 2% cholesterol for 5 or 10 days and/or constructed bile fistula. Feeding cholesterol markedly increased and bile drainage reduced plasma cholesterol concentrations. Initially, in these models there was no correlation between plasma 7alpha-hydroxy-4-cholesten-3-one concentrations and hepatic cholesterol 7alpha-hydroxylase activities (r = -0.24, n = 10). Cholesterol feeding was associated with downregulated 7alpha-hydroxylase activities, while plasma 7alpha-hydroxy-4-cholesten-3-one concentrations were elevated in the presence of increased plasma cholesterol levels. However, this discrepancy was overcome and significant correlation was observed (r = 0.73, P <.05, n = 10) by expressing 7alpha-hydroxy-4-cholesten-3-one levels relative to cholesterol. In contrast, hepatic sterol 27-hydroxylase activities were not significantly correlated with plasma absolute (r = 0.23, difference not significant [NS], n = 10) nor cholesterol-related levels of 27-hydroxycholesterol (r = -0.13, NS, n = 10), or 3beta-hydroxy-5-cholestenoic acid concentrations (r = 0.30, NS, n = 10). In conclusion, plasma 7alpha-hydroxy-4-cholesten-3-one concentrations reflected hepatic cholesterol 7alpha-hydroxylase activities when the sterol levels were adjusted to plasma cholesterol concentrations in rabbits with hypercholesterolemia. The results suggest that plasma 7alpha-hydroxy-4-cholesten-3-one relative to cholesterol is a better marker for hepatic cholesterol 7alpha-hydroxylase activity than the absolute concentration when hypercholesterolemia is present. In contrast, 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid levels in plasma did not reflect hepatic sterol 27-hydroxylase activities even if the levels were adjusted to plasma cholesterol concentrations.     

Hepatopancreatoduodenectomy with wide lymph node dissection for locally advanced carcinoma of the gallbladder--long-term results

BACKGROUND/AIMS: Although hepatopancreatoduodenectomy with wide lymph node dissection has been conducted for patients with locally advanced gallbladder carcinoma, the clinical usefulness of this radical procedure has not yet been estimated. METHODOLOGY: Morbidity, mortality, and outcome were analyzed retrospectively for 16 consecutive patients undergoing hepatopancreatoduodenectomy. RESULTS: One in-hospital fatality (6.3%) and 11 postoperative complications occurred (69%). Overall 5-year survival in this procedure was 42.9%. The 5-year survival of patients undergoing potentially curative resection (52.7%) was significantly better (P = 0.016) than those with residual tumor (0%). There was no significant correlation in 5-year survival between patients with and without lymph node metastasis. Five patients (31%) survived 5 years. Of these, 4 had Stage IVB disease, and 2 had pN2 disease. Two patients with pM1 (lymph) disease died of the disease 6 months and the other 7 months after surgery, respectively. CONCLUSIONS: Hepatopancreatoduodenectomy with wide lymph node dissection is an effective treatment for the selected patients with locally advanced gallbladder carcinoma with until pN2 disease, if curative resection is potentially feasible. Surgery is not indicated in those with pM1 (lymph) disease.     

Rigosertib induces cell death of a myelodysplastic syndrome‐derived cell line by DNA damage‐induced G2/M arrest

A multi‐kinase inhibitor, rigosertib (ON 01910.Na) has recently been highlighted as a novel type of anti‐cancer agent for the treatment of the myelodysplastic syndromes (MDS), but its action mechanisms remain to be clarified. We investigated the in vitro effects of rigosertib on an MDS‐derived cell line MDS‐L and a myeloid leukemia cell line HL‐60. Rigosertib suppressed the proliferation of both HL‐60 and MDS‐L cells and induced apoptosis by inhibition of the PI3 kinase/Akt pathway. As the effects on cell cycle, rigosertib treatment promoted the phosphorylation of histone H2AX and led to the DNA damage‐induced G2/M arrest. In addition, an immunofluorescence staining study demonstrated the abnormal localization of aurora A kinase, suggesting that rigosertib causes perturbation of spindle assembly and deregulated mitotic patterns towards cell cycle arrest and apoptosis. We also found that rigosertib exerted growth inhibitory effects on two lymphoid cell lines, Jurkat and Ramos. We further examined the molecular pathways influenced by rigosertib from the gene expression profiling data of MDS‐L cells and found a possible involvement of rigosertib treatment in the upregulation of the genes related to microtubule kinetics and the downregulation of the mRNA degradation system. The gene set enrichment analysis showed the suppression of “nonsense‐mediated mRNA decay (NMD)” as the most significantly affected gene set. These data provide a new aspect and a potential utility of rigosertib for the treatment of refractory hematopoietic malignancies.