Prevalence of hepatitis B and C virus infection in haematological malignancies and liver injury following chemotherapy

The aim of this study was to determine the carrier rate of hepatitis virus in patients with haematological malignancies and the incidence of liver injury in these patients following chemotherapy. From January 1996 to September 2002, we studied 601 consecutive, unselected series of patients with haematological malignancies admitted in our hospital unit (Japan). They consisted of 246 cases of acute leukaemia, 218 non-Hodgkin's lymphoma (NHL), 13 adult T-cell leukaemia, and 124 multiple myeloma. Of these 601 patients, 373 were men and 228 were women; their mean age was 61 yr, with a range from 18 to 89 yr. The prevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) were 7.3% and 10.1%, respectively, in NHL, both higher than those in acute leukaemia (1.7% and 2.9%, P < 0.005) and in general Japanese population (1.2% and 2.6%). The incidence of post-chemotherapy liver injury in 25 HBV carriers (36.0%) was significantly higher than that in 539 non-hepatitis virus carriers (12.6%, P = 0.003) and 37 HCV carriers (10.8%, P = 0.026). Liver injury in HBV carriers was more often present in patients who had been treated with steroids than in those without steroids (72.7% and 0%, P = 0.013). After lamivudine became available in our institution, the incidence of liver injury in HBV carriers was reduced from 53.3% to 10.0% (P = 0.041). The therapeutic strategy for haematological malignancies in hepatitis virus carriers should be further investigated.     

Efficacy of glimepiride in patients with poorly controlled insulin-treated type 2 diabetes mellitus

We retrospectively investigated the effects of adding glimepiride in patients with type 2 diabetes showing suboptimal control by insulin therapy. Of 63 patients with poorly controlled insulin-treated type 2 diabetes (baseline HbA1c, 8.4 +/- 0.6%), 32 were treated with insulin alone and 31 were given glimepiride in addition to insulin. HbA1c values, daily insulin dose, body weight, blood pressure, plasma lipid concentrations, and the number of hypoglycemic events were recorded at weeks 0, 12, 24, 36, 48, 60, and 72. HbA1c decreased by 1.1%, from 8.5 +/- 0.6% to 7.4 +/- 0.8% (P<0.0001) in patients treated with insulin plus glimepiride at 12 weeks, and improved glycemic control continued throughout the study. Required insulin dose was reduced significantly in patients treated with insulin plus glimepiride (from 29.4 +/- 14.5 to 22.3 +/- 12.1 units/day, P = 0.0187). Body weight increased significantly in patients treated with insulin plus glimepiride (from 57.0 +/- 8.7 to 59.5 +/- 9.2 kg, P = 0.0232). Adding glimepiride showed little effect on blood pressure, plasma total cholesterol, triglyceride, or HDL-cholesterol. Serum C peptide concentrations increased significantly in patients treated with insulin plus glimepiride (from 1.01 +/- 0.71 to 1.28 +/- 0.65 ng/ml, P = 0.0367). The number of hypoglycemic events did not differ between groups. Adding glimepiride to insulin therapy resulted in sustained improvement of glycemic control in patients with poorly controlled type 2 diabetes.     

Autoimmune hepatitis following allogeneic PBSCT from an HLA-matched sibling

A 7-year-old boy with acute lymphoblastic leukemia (ALL) in second remission received an allogeneic PBSCT from his HLA-matched sister. Acute grade II graft-versus-host disease (GVHD) resolved with corticosteroids. Chronic GVHD in the skin and oral mucosa at around day 60 responded to corticosteroids and cyclosporin A. At 6 months after the transplant, he developed hepatic dysfunction with elevated serum transaminases and gamma-globulin. Liver biopsy revealed chronic inflammation with lymphocytes and plasma cells in portal areas without destruction of bile ducts, suggesting autoimmune hepatitis. While rare, autoimmune hepatitis should be considered a potential long-term complication in patients with hepatic dysfunction in the late post-transplant phase.     

Diagnostic challenge to distinguish gastric duplication cyst from pancreatic cystic lesions in adult

We report herein a 63-year-old female with gastric duplication cyst (GDC), of which resected specimen was histologically shown to be composed of gastric foveolar epithelium and thin bundles of smooth muscle. Computed tomography revealed a thin-walled cystic lesion surrounded by the pancreatic tail, spleen, left kidney, and the stomach. Magnetic resonance imaging demonstrated a thin layer between the cyst and either the spleen or kidney, successfully excluding the possibility that the cyst originated from these organs. Endoscopic ultrasonography failed to show a smooth muscle bundle in the cyst wall, which is a diagnostic finding for GDC. Even retrospectively, these preoperative findings could not distinguish GDC from pancreas-originating cystic lesions. Despite the recent advances in diagnostic imaging modalities, preoperative diagnosis of GDC in adults remains difficult due in part to its rarity and the absence of characteristic findings.     

Effect of granulocyte colony-stimulating factor on bone metabolism during peripheral blood stem cell mobilization

Granulocyte colony-stimulating factor (G-CSF) has been shown to affect the biochemical markers of bone metabolism, including serum bone alkaline phosphatase (BALP), serum osteocalcin, and urine deoxypyridinoline. To determine the association between bone resorption and formation and the G-CSF-induced mobilization of peripheral blood stem cells (PBSC), we examined these markers during mobilization in 19 healthy donors. The average (+/- SEM) serum BALP level before treatment was 81.6 +/- 17.0 IU/dL, and the level increased significantly to 117.7 +/- 15.8 IU/dL on day 5 of G-CSF administration (P < .0001). The urine deoxypyridinoline level before treatment was 12.3 +/- 2.4 nmol/mmol creatinine, and this level also increased significantly to 19.4 +/- 3.0 nmol/mmol creatinine on day 5 of G-CSF administration (P < .0001). In contrast, the average level of serum osteocalcin significantly decreased from 8.07 +/- 2.88 ng/mL to 1.53 +/- 0.18 ng/mL on day 5 (P = .0353). During G-CSF administration, we also studied the serum levels of various cytokines (IL-1beta, osteoclastogenesis inhibitory factor [OCIF], IL-6, tumor necrosis factor alpha, transforming growth factor beta, interferon-gamma, macrophage colony-stimulating factor) related to bone metabolism. Only the kinetics of OCIF were significantly affected. The serum level of OCIF increased immediately after the start of G-CSF administration and remained high during G-CSF administration. These results demonstrate that high-dose G-CSF affects bone metabolism and that OCIF may play a role in bone metabolism. Consistent with the notion that G-CSF affects bone metabolism, a significant correlation was observed between CD34+ cell yield and the increase in urine deoxypyridinoline but not for the changes in serum BALP and osteocalcin levels. This result suggests that bone resorption is either directly or indirectly related to the mobilization of PBSC by G-CSF.     

Surgical anatomy of the medial segment (S4) of the liver with special reference to bile ducts and vessels

BACKGROUND/AIMS: Resection of the inferior area of the medial segment (S4a) plus S5 with preservation of the superior area of the medial segment (S4b) is being performed to manage hilar bile duct carcinoma and pT2 type gallbladder carcinoma, and thus, attention has been focused on the surgical anatomy of the medial segment of the liver to identify the specific vessels and bile ducts of the areas of that segment to be resected and to be preserved. METHODOLOGY: Anatomical study of the bile duct, portal vein, middle hepatic vein, and middle hepatic artery to the medial segment branches of the liver (S4) was performed in a total of 171 specimens comprised of 71 adult cadavers, and 100 liver casts. RESULTS: 1) Two main types of bile duct branches of the medial segment (B4) were recognized. Type I included the branches which joined to the left hepatic duct on the hilar duct side (35.5%), and type II included the branches that joined on the peripheral side (54.6%). Several subtypes were also found in both types. The B2-B3 confluence was mostly on the left (41.7%) or posterior (42.7%) to the umbilical portion (UP) of the portal vein, and to the right of the UP (hilar side) in only 15.6%. 2) The portal vein of the medial segment branches (P4): P4a branched from the right angle and upper right border of the UP in every specimen. The most common morphology was 1 large and 2-3 small branches (41%). P4b was almost always found to branch posterior to the UP and lower than P4a, and the most common morphology was 1 large and 0-1 small branches (57.8%). 3) The middle hepatic vein: In 83.2% a common trunk was observed at the confluence with the inferior vena cava, and 8 types of the middle hepatic vein were recognized. 4) The middle hepatic artery: It arose from the left hepatic artery in 61.5%, from of the right hepatic artery in 27.5%, from the proper hepatic artery in 5.5%, and from both the left and the right hepatic artery in 5.5%. CONCLUSIONS: The detailed vascular and bile duct anatomy of S4 is described. This study should be helpful in identifying the specific vessels and bile ducts of the areas of the medial segment to be resected and to be preserved, thereby facilitating resection of the medial segment.     

Relationship between blood pressure level and mortality rate: an 18-year study conducted in two rural communities in Japan

BACKGROUND: There have been very few studies on life prognosis of cardiovascular disease according to blood pressure stratification in the Japanese. Therefore, in Japan, although treatment of hypertension is possible, albeit at times difficult, due to the availability of various antihypertensive medications, the appropriate time at which treatment should be started remains a problem. OBJECTIVE: To investigate the long-term prognosis of cardiovascular disease in the Japanese general population according to blood pressure stratification in the Japanese. DESIGN: A community-based prospective cohort study of 1996 men and women between the ages of 40 and 64 years at the baseline examination was conducted over an 18-year period. Information on death was obtained from local public health nurses and death certificates. The causes of death were clarified by questionnaires sent to doctors in the hospital in which the deceased was hospitalized, and the causes of death were analysed in each blood pressure category at baseline examination. RESULTS: Mortality from cardiovascular disease increased with increases in the level of blood pressure and was significantly higher in > or = 140 mmHg group in systolic blood pressure and > or = 90 mmHg group in diastolic blood pressure, adjusted for age, sex and other cardiovascular risk factors in the Japanese general population. However, mortality risk from cardiovascular disease did not have a J-shaped relationship with systolic and diastolic blood pressure. CONCLUSION: We conclude that the optimum time for starting treatment in Japanese people is when blood pressure is 140/90 mmHg or less.     

Adenosquamous carcinoma of the pancreas: successful treatment with extended radical surgery, intraoperative radiation therapy, and locoregional chemotherapy.

BACKGROUND: Adenosquamous carcinoma of the pancreas is a rare tumor with an extremely poor survival rate. No obvious evidence that multidisciplinary treatments improves the prognosis and survival has been reported. PATIENT AND RESULTS: A 63-yr-old female with adenosquamous carcinoma of the pancreas underwent extended radical surgery, intraoperative radiation therapy, postoperative intraarterial chemotherapy, and external beam radiation therapy. The patient is alive at 40 mo after surgery with no recurrence. CONCLUSIONS: Multidisciplinary treatments including aggressive surgery, intraoperative radiation therapy, and locoregional chemotherapy might improve the survival of patients with adenosquamous carcinoma of the pancreas to inhibit liver metastasis and local recurrence.     

Curcumin inhibits glucose production in isolated mice hepatocytes

Curcumin is a compound derived from the spice turmeric, and is a potent anti-oxidant, anti-carcinogenic, and anti-hepatotoxic agent. We have investigated the acute effects of curcumin on hepatic glucose production. Gluconeogenesis and glycogenolysis in isolated hepatocytes, and gluconeogenetic enzyme activity after 120 min exposure to curcumin were measured. Hepatic gluconeogenesis from 1 mM pyruvate was inhibited in a concentration-dependent manner, with a maximal decrease of 45% at the concentration of 25 microM. After 120 min exposure to 25 microM curcumin, hepatic gluconeogenesis from 2mM dihydroxyacetone phosphate and hepatic glycogenolysis were inhibited by 35% and 20%, respectively. Insulin also inhibited hepatic gluconeogenesis from 1mM pyruvate and inhibited hepatic glycogenolysis in a concentration-dependent manner. Curcumin (25 microM) showed an additive inhibitory effect with insulin on both hepatic gluconeogenesis and glycogenolysis, indicating that curcumin inhibits hepatic glucose production in an insulin-independent manner. After 120 min exposure to 25 microM curcumin, hepatic glucose-6-phosphatase (G6Pase) activity and phosphoenolpyruvate carboxykinase (PEPCK) activity both were inhibited by 30%, but fructose-1,6-bisphosphatase (FBPase) was not reduced. After 120 min exposure to 25 microM curcumin, phosphorylation of AMP kinase alpha-Thr(172) was increased. Thus, the anti-diabetic effects of curcumin are partly due to a reduction in hepatic glucose production caused by activation of AMP kinase and inhibition of G6Pase activity and PEPCK activity.