[A case of irreversible metronidazole encephalopathy during liver abscess treatment].

Metronidazole (MNZ) is a widely used drug for protozoan and anaerobic infections. The continuous use of MNZ causes various neurological symptoms, such as cerebellar ataxia, visual disturbance, vestibulocochlear symptoms, gait disturbance, dysarthria, and epileptic seizures of unknown cause, named MNZ-induced encephalopathy (MIE), in rare cases. MIE is a reversible disease that often improves within a few days of MNZ discontinuation, but irreversible neurological symptoms rarely remain. Herein, we report a case of MIE that developed during MNZ administration for a liver abscess, causing prolonged unconsciousness and death even after drug discontinuation. An 85-year-old female patient complained of fever, elevated liver enzymes, and a multifocal abscess in the right hepatic lobe, as seen on computed tomography. Percutaneous transhepatic abscess drainage and antibiotic therapy were initiated. The causative agent of the liver abscess could not be identified, thus meropenem was started, which demonstrated no inflammation improvement, thus oral MNZ was added. The inflammation recurred when MNZ was discontinued, and the patient continued taking MNZ. Vomiting, upper limb tremors, consciousness disturbance, and convulsions appeared on day 46 (total dose of MNZ 73.5mg), and the patient was hospitalized. T2-weighted, diffusion-weighted, and FLAIR head magnetic resonance imaging (MRI) revealed symmetrical abnormal high-signal areas in the cerebellar dentate nucleus, corpus callosum, cerebral white matter, and periventricular areas. MIE was diagnosed based on the patient's course and MRI images, and MNZ was discontinued. The patient continued to suffer from impaired consciousness and convulsions after MNZ discontinuation and died due to aspiration pneumonia. Suggestively, MIE development is related to long-term MNZ administration, poor nutrition, liver disease, underlying diseases (such as advanced cancer), and serious complications. A systematic review of MIE cases revealed that 4.8-5.9% of the patients demonstrated little improvement of symptoms after MNZ discontinuation, and some deaths were reported. Patients with poor prognosis were often suffering from impaired consciousness and convulsions. Furthermore, impaired consciousness was the most common residual symptom. Abnormal signals in characteristic areas, such as the dentate nucleus cerebri and corpus callosum, on head MRI are useful for MIE diagnosis, especially in patients with abnormal findings in the cerebral white matter, which is associated with a poor prognosis. We should pay close attention to the onset of MIE when MNZ is administered.

Successful perioperative management of simultaneous transcatheter aortic valve implantation and hip fracture surgery: a case report.

A 90-year-old woman with severe aortic stenosis experienced hospital readmission for chronic heart failure exacerbations many times and was admitted to our hospital for undergoing transcatheter aortic valve implantation. Thereafter, she fell in the ward and fractured her femoral trochanter, requiring early hip fracture surgery. We proposed that we should perform simultaneous transcatheter aortic valve implantation and hip fracture surgery to cardiologist and orthopedist from anesthetic and perioperative management perspective. We considered that it was difficult to maintain cardiovascular function without cardiac intervention during hip fracture surgery and starting rehabilitation as early as possible was important. General anesthesia was induced without any complications, and the tracheal tube was removed after the successive surgeries. On postoperative day 1, bedside rehabilitation was started, and on postoperative day 3, she was transferred from the intensive care unit to the general ward. On postoperative day 32, she was transferred to another hospital. Anesthesiologist should play an important role for decision making in not only intraoperative but perioperative management for critical case, we should communicate with other departments. The successful perioperative management of simultaneous transcatheter aortic valve implantation and hip fracture surgery enabled to start rehabilitation early and prevented further patient hospitalization.

Rapidly progressed large cell neuroendocrine carcinoma of the stomach with an increased serum alpha fetoprotein level: a case report.

An 82-year-old man who had multiple hepatic tumors, a gastric tumor, and ascites was referred to our hospital. On the time of our hospital visit, he had a high serum alpha fetoprotein (AFP) level of 1206 ng/mL. Upper gastrointestinal endoscopy revealed a Borrmann Type II gastric tumor approximately 40 mm in diameter in the lesser curvature of cardia, and forceps biopsy was performed. Endoscopic ultrasound fine-needle aspiration was also performed for hepatic tumor. The biopsy specimens from the gastric and hepatic tumor were diagnosed as large cell neuroendocrine carcinoma (LCNEC), containing AFP-positive cells only sporadically by immunohistochemistry. He was diagnosed with gastric LCNEC with liver metastasis. Retrospective analysis of endoscopic data obtained at 5 months ago revealed a 0-IIc lesion, approximately 10 mm in size, in the lesser curvature of cardia, the same area of the present gastric tumor. This indicated rapid growth rate of the present tumor. The patient developed jaundice 5 days after he visited our hospital. And he died 18 days after hospital admission.

Gastric gastrointestinal stromal tumor with predominant cystic formation diagnosed by endoscopic ultrasound-fine needle aspiration.

A 69-year-old woman who had no symptoms was found to have an intraperitoneal tumor on abdominal ultrasonography in a medical checkup. Thereafter, she was referred to our hospital for a further detailed examination. Contrast-enhanced computed tomography revealed a thin-walled cystic tumor with a diameter of 8 cm and with a hypervascular solid masses in the cystic wall, along with intraperitoneal multiple nodules. The cystic tumor was contiguous with the stomach wall. For solid mass of cystic lesions, endoscopic ultrasound-fine needle aspiration was performed transgastrically with a 25-gauge Franseen needle. Pathologically, the cells in the tumor were spindle shaped with atypical nucleus and were positive for c-kit, CD34, and smooth muscle actin. The tumor was diagnosed as gastrointestinal stromal tumor (GIST). With the diagnosis of gastric GIST with peritoneal dissemination, imatinib chemotherapy was initiated.

Efficacy and safety of therapeutic endoscopic retrograde cholangiopancreatography in patients with native papillae with a performance status score of 3 or 4: A single-center retrospective study.

Objective: This study aimed to assess the efficacy and safety of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with an Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 3 or 4. Patients and Methods: We reviewed the data of 287 patients with native papillae who underwent therapeutic ERCP for biliary disease at our hospital between October 2016 and October 2018. The patients were divided into two groups; those with an ECOG-PS score of 3 or 4 (group A; n=78) and those with an ECOG-PS score of 0-2 (group B; n=209). Results: The rate of technical success was not significantly different between the two groups (95% versus 89%, P=0.13). Although the occurrence rate of overall adverse events (10% versus 11%, P=0.95) was not significantly different between the groups, the occurrence rates of aspiration pneumonia (3.8% versus 0%, P=0.0044) and heart failure (2.6% versus 0%, P=0.020) were significantly higher in group A. Conclusion: The rates of technical success and overall adverse events did not significantly differ between patients with an ECOG-PS score of 3 or 4 and those with a score of 0-2; however, aspiration pneumonia and heart failure were more likely to occur among patients with an ECOG-PS score of 3 or 4.

Hepatitis B virus X induces cell proliferation in the hepatocarcinogenesis via up-regulation of cytoplasmic p21 expression.

BACKGROUND: Hepatitis B virus X protein (HBx) has been shown to induce hepatocarcinogenesis by disrupting the functions of intracellular molecules. Cyclin-dependent kinase inhibitor p21 (Cip1/WAF1), known as a tumour-suppressor gene, has been reported to have paradoxical function, that is, acting as an oncogene, particularly when expressed in the cytoplasm. The effects of HBx on the expression and function of p21 also remain controversial. AIMS: We attempted to investigate the role of HBx in the hepatocarcinogenic process, focusing on the association with this paradoxical function of p21. The results obtained were further verified with experiments using the antihepatocarcinogenic action of interferon (IFN)-ß. METHODS: HBx transgenic mice (Xg) and HBx-transfected hepatoma cell lines were used. Intracellular localization of p21 was determined by Western blot analysis and immunofluorescence. RESULTS: Xg and HBx-transfected cells exhibited increased expression of p21. Up-regulation of p21 was positively correlated with the expression of cyclin D1 and inactive phosphorylation of retinoblastoma protein (pRb). These HBx-induced cell proliferative responses were cancelled by knockdown of p21, which resulted in growth reduction in HBx-expressing cells, suggesting the oncogenic properties of HBx-induced p21. HBx induced accumulation of p21 in the cytoplasm, and activation of PKCα was involved. Finally, IFN-ß-treated Xg liver, as well as hepatoma cells, showed a shift of cytoplasmic p21 to the nucleus, accompanied by the abrogation of HBx-induced oncogenic modulation. CONCLUSIONS: Our results suggest that HBx induces hepatocarcinogenesis via PKCα-mediated overexpression of cytoplasmic p21 and IFN-ß suppressed these molecular events by shifting p21 to the nucleus.

Progression of hypermethylation of the p16(INK4A) gene from normal liver to nontumorous liver and hepatocellular carcinoma: an evaluation using quantitative PCR analysis.

The aim of this study was to determine to what extent hypermethylation of the p16(INK4A) (p16) gene promoter is increased in nontumorous liver tissues compared with in normal liver, using two quantitative methylation-specific polymerase chain reaction (MS-PCR) methods and a bisulfite sequencing method. Methylation of the p16 gene was detected more frequently in nontumorous liver than in normal liver using the TaqMan PCR method. Methylation indices also were significantly higher in nontumorous than in normal liver. However, the bisulfite sequencing method did not detect significantly more methylation of the p16 gene in nontumorous than normal liver, nor was there a significant difference in the level of p16 mRNA. There may be a greater proportion of cells which contain methylated p16 in nontumorous than in normal liver. However, the difference was so small that the functional relevance to hepatocarcinogenesis remains elusive.

Serum alpha-fetoprotein levels during and after interferon therapy and the development of hepatocellular carcinoma in patients with chronic hepatitis C.

The association between serum alpha-fetoprotein (AFP) levels during and after interferon (IFN) therapy and the development of hepatocellular carcinoma (HCC) was evaluated in patients with chronic hepatitis C (CHC). A total of 263 patients treated by IFN with or without ribavirin were enrolled in the study. Serum AFP levels during and after IFN therapy were investigated retrospectively, and statistical analysis was performed to identify the factors associated with HCC development. During IFN therapy, serum AFP levels significantly decreased, regardless of virologic response to treatment. Increased serum AFP levels (>or=10 ng/ml) at the end of IFN therapy (EOT) was a close-to-significant variable affecting the development of HCC (P = 0.057), and a significantly higher cumulative incidence of HCC was seen in patients with increased serum AFP levels at EOT (P = 0.021). Serum AFP level at EOT is a possible predictor of HCC in CHC patients after IFN therapy.

Temporal treatment with interferon-beta prevents hepatocellular carcinoma in hepatitis B virus X gene transgenic mice.

BACKGROUND/AIMS: The preventive effect of interferon (IFN) against hepatocellular carcinoma (HCC) has been confirmed clinically. We sought to determine whether the temporal administration of IFN-beta prevents hepatocarcinogenesis in a mouse model where HCC develops without necroinflammation. METHODS: Hepatocarcinogenic mice that are transgenic for the hepatitis B virus X gene (HBx-Tg) were treated with IFN-beta or saline (control) for three months, from 3 to 6 months of age, and the incidence of HCC was determined at 18 months of age. The effects of IFN-beta on DNA synthesis and apoptosis were tested. RESULTS: The incidence of HCC was significantly lower in the IFN-beta-treated mice than the controls (0 vs. 50%, P<0.01). Inhibition of DNA synthesis in hepatocytes by IFN-beta was observed in the livers of HBx-Tg, without any significant induction of apoptosis. Although the treatment of IFN-beta was temporal, the number of hepatocytes with DNA synthesis remained lower 3 and 12 months later in life. CONCLUSIONS: Temporal administration of IFN-beta has a significant preventive effect on the occurrence of HCC in a mouse model where HCC develops without inflammation. The mechanisms are the inhibition of DNA synthesis and cell cycle progression of hepatocytes.