Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.     

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor,BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol.
2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats, New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC₅₀ was 1.0 μM in SD rats. 2.1 μM in NZ white rabbits, and 0.3 μM in WHHL rabbits. With human SMC, the value was 0.02 μM in the presence of 10% FCS and 0.2 μM with a mixture of growth factors.
3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg⁻¹ day⁻¹. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P<0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P<0.05). By anti-α smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P<0.01).
4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

     

Clinicopathological features of hereditary breast cancer

The possible role of germline mutations ofBRCA1 andBRCA2 as causative agents of familial breast cancer was assessed. Their possible involvement in the carcinogenesis of hereditary breast cancer was investigated using 63 clinically suspect families. Twenty-one lineages (33.3%) had mutations in one of the twoBRCA genes. This relatively low incidence suggested that germline mutations in unknown genes are involved in the carcinogenesis of hereditary breast cancer in the Japanese population. However, the clinicopathological features characteristic of hereditary breast cancer, such as early disease onset, a high incidence of bilateral breast cancer, and a high incidence of multiple primary carcinomas in other organs were confirmed in the present study.     

The development of a small bowel volvulus in the early postoperative period following a distal gastrectomy: Report of a case

A 51-year-old Japanese man who underwent a standard distal gastrectomy for cancer of the stomach developed abdominal pain when oral intake was commenced on the 6th postoperative day after an uneventful postoperative course. Complete obstruction of the jejunum led to a sudden deterioration in his general condition and a laparotomy was performed, revealing counterclockwise rotation of the mesenterium. The necrotic portion of the small intestine was removed, while 10 cm of the upper jejunum and 100 cm of the terminal ileum were preserved. His second postoperative course was uneventful apart from the development of intestinal hurry, which is now under medical control 9 months after his second laparotomy.     

The effects of oligomers content and surface morphology on foreign-body tumorigenesis with polyetherurethanes: two years subcutaneous implantation study in rats

Three polyurethane materials were prepared by removing and adding the leachable oligomers from and to the same polyetherurethane (PEU). The three PEU materials were dissolved in tetrahydrofuran (THF) and dimethyformamide (DMF) and the solutions were cast on a glass plate to make films of smooth and foamed surfaces, respectively. These six materials and polydimethylsioxane (silicone) were implanted into subcutaneous pocket of rats for 2 years to evaluate the long-term effects around the implant. Among the smooth surface implants, PEU materials induced a higher incidence of tissue responses, including tumor formation than silicone. However, no relationship between the oligomer content and the tissue responses was found. Changing surface morphology from a smooth to a foamed one prolonged the latent period of tumor development and decreased the total tumor incidence.     

Usefulness of magnetic resonance imaging for the diagnosis of superior lumbar hernia: a case report

A 48-year-old man consulted us with the chief complaints of right flank mass. On examination, there was a soft bulge on the right superior lumbar area. Since computed tomographic scanning showed subcutaneous fatty tissue, we suspected a superior lumbar hernia. The diagnosis was confirmed by magnetic resonance imaging (MRI) that revealed a lumbar muscle defect and prolapsed fatty tissue around the kidney. During the operation, a small hernia hiatus, 2 cm in width, opened in the superior lumbar triangle. The herniated fatty tissue was excised, and the defect of fascia was closed by overlapping the adjacent fascial structure. No signs of recurrence were found at 3 months postoperatively. The usefulness of MRI for the diagnosis is discussed and previous literature is reviewed.     

Psychogenic lower urinary tract dysfunction in women: patho-physiological investigation for psychogenic frequency-urgency syndrome and psychogenic urinary retention]

PURPOSE: Psychogenic lower urinary tract dysfunction (PLUTD) is composed of two syndromes; psychogenic frequency-urgency syndrome (PFUS) and psychogenic urinary retention (PUR). We evaluated the patho-physiology of PFUS and PUR, and explored the different pathogenesis in these syndromes. MATERIAL AND METHODS: Forty five patients with PLUTD, consisting of 23 patients with PFUS and 22 patients with PUR were investigated by using the psychological tests: CMI (Cornell Medical Index) and TEG (Todai's Egogram), a quantitative perspiration test in 45 females (23 patients with PFUS and 22 patients with PUR), and simultaneous measurements of voiding cysto-urethrography and urodynamic studies using the Life-Tech 6 channel polygraph in 35 patients (17 patients with PFUS and 18 patients with PUR). RESULTS: The prevalence in ages revealed two peaks, 20 years and 50 to 60 years. Over 25% of them had pyuria more than 10/hpf of WBC. Peak flow rate measured by uroflowmetry showed normal range in PFUS group and decreased in PUR group. The functional vesical volume was less than 100 ml in most patients with PFUS. Residual urine in PUR group was significantly greater. Capacity of the PFUS group were able to hold over 400 ml of contrast instilled through the urethral catheter, despite increased desire to void. Over 15% of the study group with PFUS showed uninhibited systolic contraction of detrusor (> 15 cm H2O) during filling phase. The measurement value of urodynamic parameters demonstrated that a periodic follow-up survey of the upper urinary tract should be performed because of the low compliance bladder in the patients with PLUTD. During voiding phase, the women with PFUS had a tendency to be divided into two groups, hypercontractile or acontractile detrusor. The voiding cysto-urethrography (VCUG) showed a tendency of bladder neck opening on patients with PFUS during filling phase. Most of PLUTD cases demonstrated a round to triangle shape on vesical configuration, which led to a spastic condition of detrusor muscle. We attempted to measure the quantitative perspiration using 3 kinds of loading tests; respiratory, arithmetic and psychological load. In the psychological loading test, we asked 98 questions about their daily lives including occupation, living condition, family relationship and sexual activities. Arithmetic loading test consisted of counting in reverse, subtraction and multiplication. The quantitative perspiration rate resulted in a "positive" in many patients with PFUS. Respiration loading test was performed to measure the respiration volume during 3 large inhales. Most patients with PUR tested within the normal range for respiration except for those patients with decreased or no perspiration during the psychiatric loading test. These results may reflect the psychological elements including suppression and subconscious defense mechanism. Neurosis which was diagnosed as having type III to type IV of the Cornell Medical Index was demonstrated in less than under 40% of patients with PFUS and more than 55% patients with PUR. There was no significant trend or difference between PFUS and PUR detected from Todai's Egogram. CONCLUSIONS: Due to the reflection of many psychological responses, it is necessary to investigate from various examinations including psychological, autonomical and classical urological studies for accurate diagnosis of PLUTD.     

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis. BACKGROUND: 22-Oxacalcitriol (OCT) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PTH) secretion in uremic rats. This study was performed to examine the long-term effect of intravenously administered OCT on high-turnover bone disease in model rats of slowly progressive renal failure. METHODS: Slowly progressive renal failure rats were made by a single injection of glycopeptide isolated from rat renal cortical tissues. At 250 days, glycopeptide-induced nephritis (GN) rats were divided into three groups with the same levels of serum creatinine and PTH, and they received either OCT (0.03 or 0.15 microg/kg body wt) or vehicle given intravenously three times per week for 15 weeks. RESULTS: Renal function of GN rats deteriorated very slowly but progressively, as assessed by the increase of serum creatinine concentration. At sacrifice, serum PTH levels, bone formation markers, bone resorption markers, and fibrosis volume were significantly elevated in vehicle-treated GN rats compared with those of sham-operated rats, suggesting the development of high-turnover bone disease with osteitis fibrosa. In contrast, in the GN-OCT 0.15 microg/kg group, these high PTH levels and high-turnover bone and fibrosis were significantly decreased. Such amelioration of bone abnormalities by OCT was not accompanied by either hypercalcemia or further deterioration of renal function. CONCLUSIONS: These data indicate that OCT may be a useful and safe agent not only for the suppression of PTH, but also for the amelioration of osteitis fibrosa and high-turnover bone without causing hypercalcemia in chronic dialysis patients.     

Operative approach to mediosuperior cerebellar tumors: occipital interhemispheric transtentorial approach

BACKGROUND: The transtentorial approach is well known as an approach to the pineal region. We have modified this approach for mediosuperior cerebellar tumors. METHODS: We describe six cases of tumor excision in this region using an occipital interhemispheric transtentorial approach. RESULTS: The lesions were easily accessible and the tumor was totally removed by this modified approach in all cases. Transient visual field disturbance with spontaneous recovery occurred in two patients. The lateral margin of the tumor was accessed easily up to 35 mm from the midline on the operative side and up to 17 mm from the midline on the contralateral side. CONCLUSION: This approach proved to be very useful for mediosuperior lesions of the cerebellum, without causing any neural structural damage, and allowed for a wider operative field.