[Solitary lymph node metastasis from early-stage hepatocellular carcinoma after transcatheter arterial chemoembolization and radiofrequency ablation: a case report and review of the Japanese literature].

A 77-year-old man with chronic hepatitis C underwent transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC) in segment 8 of the liver. Necrosis was confirmed radiologically. After 19 months, recurrent HCC in segment 6 was treated with TACE and RFA. There was no recurrence. Direct-acting antiviral (DAA) therapy 24 months after the initial procedure led to a sustained virologic response. AFP-L3 markedly increased 11 months after DAA therapy, and MRI 6 months after that showed a solitary lymph node near the common bile duct. Because no intrahepatic recurrence or other lymph nodes were seen, the solitary node was excised. Histopathology showed metastatic HCC. There has been no subsequent recurrence over 13 months of follow-up.

[A Resected Case of Retroperitoneal Metastasis and Small Bowel Metastasis from HCC].

A 71-year-old man underwent right hemi-hepatectomyfor a hepatocellular carcinoma(HCC)measuring 18 cm in diameter. The pathological diagnosis was poorlydifferentiated HCC. Ten months after the surgery, computed tomographyrevealed a nodule 12mm in diameter in the right lung as well as 2 nodules measuring 19 and 11mm in diameter in the retroperitoneum at the cranial aspect of the left kidney. Four months later, the nodule in the right lung had enlarged to 44 mm, while the 2 nodules in the retroperitoneum had enlarged to 68mm and 34 mm. These nodules were resected and histopathologicallydiagnosed as metastasis from HCC. Twenty-one months after liver resection, computed tomographyrevealed nodules 16 and 25mm in diameter in the retroperitoneum around the urinarybladder and jejunum, respectively. One month later, intussusception resulted from the jejunal tumor. Laparoscopic surgerywas performed for both tumors, which were diagnosed as metastases from HCC. Twenty-five months after liver resection, metastasis from the HCC appeared in the left adrenal grand, at the site of the jejunal anastomosis, and in the fattytissue around the right scapula. Twenty-nine months after liver resection, the patient died of respiratoryfailure from multiple metastases in the left lung.

[A Case of Rupture of Esophageal Varices during a Course of CAPOX with Bevacizumab Therapy for Sigmoid Colon Cancer with Multiple Liver Metastases].

The patient was a 67-year-old man with multiple liver metastases from sigmoid colon cancer and had received capecitabine, oxaliplatin, and bevacizumab(CAPOX plus Bev)combination chemotherapy. After 11 courses of this therapy, he had a rupture of esophageal varices and was treated with endoscopic variceal ligation(EVL). Esophageal varices are rare during the course of oxaliplatin-based chemotherapy. More studies are necessary for early detection of esophageal varices during this therapy.

Putting "sticky notes" on the electronic medical record to promote intra-hospital referral of hepatitis B and C virus-positive patients to hepatology specialists: an exploratory study.

BACKGROUND: Currently, no system for appropriate intra-hospital collaboration regarding hepatitis virus positive individuals exists, even in medical institutions with hepatologists among their staff. The main objective of this study was to explore a simple alert system to promote the referral of patients with hepatitis B surface antigen (HBsAg)- or anti-hepatitis C virus (HCV) antibodies positivity to hepatologists through electronic medical records. METHODS: Since April 2014 at Osaka City Juso Hospital, "sticky notes" have been put on the electronic medical records of patients newly diagnosed with HBsAg- or anti-HCV- antibodies positivity to recommend intra-hospital referral of those patients to specialists. In this study, we investigated the number of referrals to hepatologists before vs. after the introduction of this system (that is, in fiscal years 2013 [Period 1] and 2014 [Period 2], respectively), and the subsequent clinical courses of the patients. RESULTS: The proportions of patients with HBsAg and anti-HCV antibody positivity did not show statistically significant differences between Period 1 and Period 2 (1.6 % [43/2,757] vs. 1.3 % [39/2,891], p = 0.58; and 5.8 % [156/2,674] vs. 5.3 % [147/2,790], p = 0.39, respectively). However, the referral proportions for patients with HBsAg- and anti-HCV antibody positivity were significantly higher in Period 2 (73 % [11/15] and 65 % [41/63], respectively) than in Period 1 (28 % [5/18] and 17 % [9/54]) (p = 0.009 and p < 0.001, respectively). Among patients who were referred to hepatologists, 2 HBsAg-positive and 4 anti-HCV antibody positive patients initiated antiviral treatment. CONCLUSION: Our simple electronic medical record based alert system effectively promoted intra-hospital referral of hepatitis virus-positive patients, who have been detected by screening tests, to hepatologists.

The Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) is more useful than pre-existing laboratory tests for predicting hazardous drinking: a cross-sectional study.

BACKGROUND: It is important to screen for alcohol consumption and drinking customs in a standardized manner. The aim of this study was 1) to investigate whether the AUDIT score is useful for predicting hazardous drinking using optimal cutoff scores and 2) to use multivariate analysis to evaluate whether the AUDIT score was more useful than pre-existing laboratory tests for predicting hazardous drinking. METHODS: A cross-sectional study using the Alcohol Use Disorders Identification Test (AUDIT) was conducted in 334 outpatients who consulted our internal medicine department. The patients completed self-reported questionnaires and underwent a diagnostic interview, physical examination, and laboratory testing. RESULTS: Forty (23 %) male patients reported daily alcohol consumption ≥ 40 g, and 16 (10 %) female patients reported consumption ≥ 20 g. The optimal cutoff values of hazardous drinking were calculated using a 10-fold cross validation, resulting in an optimal AUDIT score cutoff of 8.2, with a sensitivity of 95.5 %, specificity of 87.0 %, false positive rate of 13.0 %, false negative rate of 4.5 %, and area under the receiver operating characteristic curve of 0.97. Multivariate analysis revealed that the most popular short version of the AUDIT consisting solely of its three consumption items (AUDIT-C) and patient sex were significantly associated with hazardous drinking. The aspartate transaminase (AST)/alanine transaminase (ALT) ratio and mean corpuscular volume (MCV) were weakly significant. CONCLUSIONS: This study showed that the AUDIT score and particularly the AUDIT-C score were more useful than the AST/ALT ratio and MCV for predicting hazardous drinking.

The Alcohol Use Disorders. Identification Test (AUDIT) score is useful for predicting alcohol consumption.

It is important to screen for alcohol consumption and drinking customs by using a stan- dardized method. The aim of this study was to investigate whether standardized questionnaire was useful for predicting alcohol consumption. A cross-sectional study using the Alcohol Use Disorders Identification Test (AUDIT) was conducted in 334 outpatients who consulted the Internal Medicine Department of Osaka City Juso Hospital. The patients completed self-reported questionnaires and underwent a diagnostic interview, physical examination, and laboratory testing. Forty (23%) male patients reported daily alcohol consumption 40 g, and 16 (10%) female patients reported consumption 20 g. The optimal cutoff values of hazardous drinking (all patients)/ drinker (male)/ drinker (female) were calculated using a 10-fold cross validation, resulting in an optimal AUDIT score cutoff of 8.2/ 7.2/ 6.1, with sensitivity of 95.5%/ 96.3%/ 88.9%, specificity of 87.0%/ 96.3%/ 88.9%, false positive rate of 13.0%/ 9.4%/6.6%, false negative rate of 4.5%/ 3.'%/ 11.1%, and area under the receiver operating characteristic curve of 0.97/ 0.98/ 0.99. In conclusion, this study showed that the AUDIT score was useful for predicting alcohol consumption.

Pulmonary rehabilitation program including respiratory conditioning for chronic obstructive pulmonary disease (COPD): Improved hyperinflation and expiratory flow during tidal breathing.

BACKGROUND: Pulmonary rehabilitation has generally relieved symptoms, strengthened exercise endurance and improved health-related quality of life (QOL) in patients with COPD, but recovery of pulmonary function remains questionable. This analysis of our innovative rehabilitation program is directed at documenting changes in patients' expiratory airflow limitation, pulmonary symptoms and QOL. This program is designed to provide "respiratory conditioning", a physical therapist-assisted intensive flexibility training that focuses on stretching and rib cage mobilization. METHODS: Thirty-one patients with COPD who attended rehabilitation sessions at Juntendo University Hospital from 1999 to 2006 were analyzed. Pulmonary function, expiratory flow limitation during tidal breathing, six minute walk distance (6MWD), respiratory muscle strength, and St. George Respiratory Questionnaire (SGRQ) were measured before and after pulmonary rehabilitation. RESULTS: In participants ages 68±7 years, the FEV(1)% predicted was 39.3±15.7%. 6MWD, SGRQ and respiratory muscle strength were significantly improved after pulmonary rehabilitation. Although neither FEV(1)% predicted nor FEV(1)/FVC was affected to a significant extent, indicating little effect on airflow limitation, expiratory flow limitation in supine as well as seated during tidal breathing improved significantly. Moreover, rehabilitation significantly diminished TLC% predicted, FRC% predicted, RV% predicted and RV/TLC values, thus indicating a reduction of hyperinflation of the lungs at rest. CONCLUSIONS: The present results suggest that our rehabilitation program with respiratory conditioning significantly lowered the hyperinflation of lungs at rest as well as the expiratory flow limitation during tidal breathing. In patients with COPD, overall pulmonary function improved, exercise endurance increased and health-related QOL was enhanced.

Incremental increases in glucocorticoid doses may reduce the risk of osmotic demyelination syndrome in a patient with hyponatremia due to central adrenal insufficiency.

A 50-year-old man was admitted to our hospital because of general malaise. Laboratory tests revealed severe hyponatremia (104 mEq/L), which was attributed to central adrenal insufficiency. To treat presumed central diabetes insipidus (CDI), we administered a small dose of hydrocortisone and gradually increased it to maintenance doses to prevent osmotic demyelination syndrome (ODS). Serum sodium levels did not increase more than 10 mEq/L/day and ODS did not occur. Thereafter, the patient was proven to have CDI. Incremental increases in glucocorticoid dose may reduce the risk of ODS for patients with hyponatremia due to central adrenal insufficiency, especially that complicated by CDI.

Favorable factors for re-treatment with pegylated interferon α2a plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus.

AIM: Effect of re-treatment for pegylated interferon (PEG-IFN) plus ribavirin was not fully evaluated. We examined the effects of re-treatment with PEG-IFN plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus who failed to achieve a sustained virological response (SVR) with combination therapy. METHODS: We examined 38 patients who were re-treated with PEG-IFN α2a plus ribavirin for more than 60 weeks, among whom 14 were non-responders and 24 were relapsers after previous treatment with PEG-IFN α2b plus ribavirin. IL28B genotyping was done in 21 patients. RESULTS: The overall SVR rate was 34%. Analysis of baseline characteristics showed that the relapsers had a significantly higher SVR rate than the non-responders (50.0%, 12/24 vs. 7.1%, 1/14, respectively, P = 0.012) The SVR rates of re-treated patients who had turned hepatitis C virus (HCV) RNA-negative at weeks 8, 12, 24, and 48 of the previous therapy were 67% (4/6), 67% (4/6), 29% (2/7), and 25% (1/4), respectively. Re-treatment achieved an SVR in five of 12 patients with IL28B major alleles and three of nine patients with IL28B minor alleles. During the re-treatment, patients with complete viral suppression at week-12 achieved a significantly higher SVR rate (P = 0.001). CONCLUSIONS: Re-treatment with PEG-IFN α2a plus ribavirin therapy is effective in patients who relapse after a course of PEG-IFN α2b plus ribavirin therapy. Re-treatment is a particularly useful option for patients who achieve early viral clearance during previous therapy.

[A case of ruptured ileal varices associated with alcoholic liver cirrhosis].

The case was a 33-year-old woman with alcoholic liver cirrhosis. Her chief complaint was melena. She had undergone the abdominal operation in the past. Upper and lower gastrointestinal endoscopy did not reveal the bleeding point in the gastrointestinal tract. We diagnosed the bleeding from the ileocecum by the hemorrhage scintigraphy, the superior mesenteric artery angiography, and CT angiography. She had varices at the terminal ileum and adhesion between the ovary and the ileum end. The subtotal resection of the ileum was performed.

[Usefulness of fentanyl patch (Durotep) in cancer patients when rotated from morphine preparations].

BACKGROUND: [corrected] The transdermal fentanyl patch (Durote patch) is an opioid preparation requiring replacement once in three days, which is occasionally prescribed to replace morphine preparations. The conversion ratio from morphine to fentanyl has been claimed to be 100:1 or 150:1, but there may exist individual variations. METHODS: We retrospectively evaluated the analgesic effects and adverse effects of fentanyl patch in 24 cases among 22 patients (11 men and 11 women). RESULTS: There were some reasons for switching; the major one was for home-care. In most cases rotation was completed in a few days and the side effects disappearance or were reduced, but 4 cases of them showed severe diarrhea or exhibited exacerbation of the pain, and had to go back to morphine. There were a wide variations of conversion ratio with a mean of 96.6. CONCLUSIONS: The fentanyl patch is a useful agent to control severe cancer pain because of excellent analgesic effect, less adverse effects and more convenience as well as itsundesirable characteristics when transition of patients to home-care is considered or oral administration should be avoided. Above all it offers a great possibility to improve cancer patient's quality of life.

A role of the adrenal gland in stress-induced up-regulation of cytokines in plasma.

To reveal a pathway by which psychological/physical stresses influence host defense capability, responses to immobilization stress in mice were investigated, focusing on a multifunctional cytokine, interleukin-18 (IL-18). Immobilization stress induced interleukin-18 accumulation in plasma and in the adrenal gland. Inhibition on ACTH resulted in suppressed levels of IL-18 both in plasma and the adrenal gland. In hemi-adrenalectomized mice, plasma IL-18 levels after stress were lower than in sham-operated mice. This, together with the observation in stressed hemi-adrenalectomized mice that IL-6 levels in plasma were suppressed but up-regulated by recombinant IL-18, showed that the adrenal gland plays a crucial role in stress-related elevation of IL-6 in plasma via IL-18. Adrenal gland is highlighted as an organ connecting the psychological, endocrine, and immune systems. Controlling the secretion of IL-18 from the adrenal gland may serve as a possible preventative means against a stress-related disruption of host defenses.

Identification of altered protein expression and post-translational modifications in primary colorectal cancer by using agarose two-dimensional gel electrophoresis.

PURPOSE: Although numerous proteome studies have been performed recently to identify cancer-related changes in protein expression, only a limited display of relatively abundant proteins has been identified. The aim of this study is to identify novel proteins as potential tumor markers in primary colorectal cancer tissues using a high-resolution two-dimensional gel electrophoresis (2-DE). EXPERIMENTAL DESIGN: 2-DE using an agarose gel for isoelectric focusing was used to compare protein profiling of 10 colorectal cancer tissues and adjacent normal mucosa. Altered expression and post-translational modification of several proteins were examined using Western blot analysis and immunohistochemistry. RESULTS: Ninety-seven proteins of 107 spots (90.7%) that were differentially expressed between matched normal and tumor tissues were identified by mass spectrometry. Among them, 42 unique proteins (49 spots) significantly increased or decreased in the tumors. They include eukaryotic translation initiation factor 4H, inorganic pyrophosphatase, anterior gradient 2 homologue, aldolase A, and chloride intracellular channel 1, whose elevated expression in tumor tissues was confirmed by Western blot analysis and immunohistochemistry. Interestingly, only isoform 1 of two transcript variants of eukaryotic translation initiation factor 4H was greatly up-regulated in most of the tumor tissues. Moreover, post-translational modifications of the prolyl-4-hydroxylase beta subunit and annexin A2 also were identified. CONCLUSIONS: We identified several novel proteins with altered expression in primary colorectal cancer using agarose 2-DE. This method is a powerful technique with which to search for not only quantitative but also qualitative changes in a biological process of interest and may contribute to the deeper understanding of underlying mechanisms of human cancer.

Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer.

Aneuploidy is the hallmark of many human cancers. Recent work has strongly suggested that chromosome missegregation during mitosis is the main cause of aneuploidy and contributes to oncogenesis. Centromere protein (CENP)-A is the centromere-specific histone-H3-like variant essential for centromere structure and function. It plays a central role in the assembly of the protein complex, termed kinetochore, which is indispensable for equal chromosome segregation. In this study, we demonstrate that the kinetochore protein CENP-A was overexpressed in all of 11 primary human colorectal cancer tissues. CENP-A mRNA was also up-regulated, indicating that overexpression of CENP-A occurred at the transcriptional level. Immunostaining with anti-CENP-A antibodies showed increased CENP-A signals in the tumor cells. Moreover, coimmunostaining of CENP-B, a centromere-associated DNA binding protein, with CENP-A showed mistargeting of CENP-A to noncentromeric chromatin in the tumor cells. These results suggest that overexpression of CENP-A could play an important role for aneuploidy in colorectal cancers.