Management of enterovesical fistula in patients with Crohn's disease

PURPOSE: Enterovesical fistula in patients with Crohn's disease is intractable. Although there are some reports that the enterovesical fistula were successfully treated conservatively, closure of the fistula cannot always be achieved and surgical intervention may required for those patients. Since surgical closure of entero-entero fistula has a high risk of relapse, the strategy for treating enterovesical fistula has not been established. We evaluated the clinical findings especially in management of enterovesical fistula in Crohn's disease. PATIENTS AND METHODS: Two hundred two patients (mean age was 28.4 year old, range 12-69; 152 men and 50 women) were diagnosed as Crohn's disease during a period of 15 years between 1986 and 2000 in our institute. The incidence and the clinical results regarding the diagnosis and the treatment of enterovesical fistula in these patients were retrospectively evaluated. RESULTS: Seven in 202 patients were diagnosed to have an enterovesical fistula (3.5%, 6 men and 1 woman). The period from the initial diagnosis of Crohn's disease to the recognition of the enterovesical fistula was 11 to 204 months (mean 92.1 months). Enterovesical fistula was revealed and/or visualized by radiological enterography in 6, cystography in 2, cystoscopy in 6, and CT in 4 patients. Surgical interventions were finally conducted in all 7 patients after the failure of conservative treatment for 10 to 146 days (mean 68.2 days). Surgical procedures performed for closing the enterovesical fistula were partial cystectomy with fistulectomy in 5, fistulectomy with bladder wall overlay-suture in 2, and bladder wall overlay-suture alone in 1. No relapse of enterovesical fistula was recognized in any patient in the average observation of 41.6 months. CONCLUSION: Although the treatment of Crohn's disease has been advanced, enterovesical fistula is shown to be resistant to conservative treatment options and it makes patients in unfavorable status for relatively long duration. Our evaluation shown here demonstrated the sufficient surgical results on the closure of enterovesical fistula without any relapse, and was different from the high relapse rate after the surgical management of entero-entero fistula in similar observation period. Surgical interventions of enterovesical fistula caused by Crohn's disease might have an advantage to make diseased patients improved in shorter duration.     

CCAAT/enhancer-binding protein-d is induced in mesangial area during the early stages of anti-Thy1.1 glomerulonephritis and regulates cell proliferation and inflammatory gene expression in cultured rat mesangial cells

Background Interleukin (IL)-6, cyclooxygenase (COX)-2, and monocyte chemoattractant protein (MCP)-1 contribute to renal injury. The promoter regions of these genes contain CCAAT/enhancer-binding protein (C/EBP)-binding sites. In this study, we investigated the role of C/EBP-δ in mesangial cells (MCs). Methods In an in vivo study, anti-Thy 1.1 glomerulonephritis rats were generated and C/EBP-δ, IL-6, COX-2, and MCP-1 expressions were assessed by immunohistochemistry. In an in vitro study, cultured MCs were transfected with non-silencing (NS) short interfering RNA (siRNA) or C/EBP-δ siRNA. Subsequently, after stimulation with IL-1β, C/EBP-δ, IL-6, COX-2, and MCP-1 mRNA expression levels were evaluated using real-time polymerase chain reaction (PCR). IL-6 concentration in the culture medium was determined by enzyme-linked immunosorbent assay. In addition, cell proliferative activity against IL-1β or platelet-derived growth factor-BB was assessed by bromodeoxyuridine incorporation. Results In the in vivo study, C/EBP-δ, IL-6, COX-2, and MCP-1 were expressed in the mesangial region of anti-Thy 1.1 glomerulonephritis rats on day 1. In the in vitro study, IL-1β increased C/EBP-δ mRNA levels in NS siRNA-transfected MCs (7.3-fold), but no increase was evident in C/EBP-δ siRNA-transfected MCs. IL-6, COX-2, and MCP-1 mRNA levels in C/EBP-δ siRNA-transfected MCs were all lower than those in NS siRNA-transfected MCs (decreases of 57.7%, 85.7%, and 69.3%, respectively). The IL-6 concentration in the culture medium from C/EBP-δ siRNA transfected MCs (7.37 ± 4.3 pg/ml) was also lower than that in the culture medium from NS siRNA-transfected MCs (25.2 ± 3.4 pg/ml). Cell proliferative activity in C/EBP-δ siRNA-transfected MCs was lower than that in NS siRNA transfected MCs. Conclusions C/EBP-δ was induced in the mesangial region during the early stages of anti-Thy1.1 glomerulonephritis. C/EBP-δ contributes to inflammatory gene expression and MC proliferation.     

Analysis of surgical treatment of Masaoka stage III-IV thymic epithelial tumors

Objective

The purpose of this study is to elucidate the outcomes after surgical resection of Masaoka stage III-IV thymic epithelial tumors.

Methods

We retrospectively reviewed patients with Masaoka stage III-IV thymic epithelial tumor who underwent surgical resection from January 1995 to January 2017. The clinicopathological features, surgical procedures, and postoperative outcomes were investigated.

Results

Thirteen patients with thymoma and 18 patients with thymic carcinoma were assessed. The postoperative Masaoka stages were III/IVa/IVb?=?8/4/1 in thymoma and III/IVa/IVb?=?11/2/5 in thymic carcinoma. In patients with thymoma, the World Health Organization pathological subtypes were A/B1/B2/B3?=?2/1/4/6. We performed combined resection and reconstruction for brachiocephalic vein or superior vena cava in 3 patients with thymoma and 7 patients with thymic carcinoma. In all patients, the patency rate of the grafts was very low for the left brachiocephalic vein and well maintained for the right brachiocephalic vein. Macroscopically and pathologically complete resection was achieved in 11 and 6 patients with thymoma, respectively, and in 15 and 9 patients with thymic carcinoma, respectively. The 10-year survival rates were 85.7% in thymoma and 70.3% in thymic carcinoma. Postoperative recurrences were observed in 2 and 9 patients with thymoma and thymic carcinoma, respectively. Recurrences were observed within 5 and 10 years after surgery in 2 patients with thymoma and within 2 years in all patients with thymic carcinoma.

Conclusions

Patients with Masaoka stage III-IV thymic epithelial tumor showed relatively favorable long-term survival after surgical treatment. Therefore, aggressive surgical resection for complete resection may be a treatment option for these conditions.

     

Stereotactic radiosurgery/radiotherapy for pituitary adenomas: a review of recent literature

The recent clinical results are reviewed of stereotactic radiosurgery/radiotherapy for the treatment of pituitary adenomas. The outcomes of pituitary adenomas treated by stereotactic radiosurgery/radiotherapy with gamma knife, CyberKnife, or linear accelerator (LINAC) radiosurgery were evaluated from articles published after 2004. Each study was evaluated for the number of patients, radiosurgical parameter (marginal dose), length of follow up, tumor growth control, rate of hormonal normalization in secretary adenomas, and adverse events. After gamma knife radiosurgery, the tumor reduction rates varied from 42.3% to 89% in non-secreting adenomas. However, the tumor control rates in non-secreting adenomas were more than 90% in most studies. In growth hormone-secreting adenomas, the rates of insulin-like growth factor-1 normalization ranged from 36.9% to 82%. In adrenocorticotropin-secreting adenomas, the rates for 24-hour urine free cortisol normalization ranged from 27.9% to 54%. In prolactin-secreting adenomas, the prolactin normalization ranged from 17.4% to 50%. New hormonal deficits ranged from 0% to 34%. New visual deficits were relatively low. The number of patients treated with CyberKnife and LINAC radiosurgery/radiotherapy was small and follow-up periods were relatively short compared to those with gamma knife treatment, but the clinical outcomes after these therapies were similar to those after gamma knife therapy. Image-guided stereotactic radiosurgery/radiotherapy with the gamma knife, CyberKnife, or LINAC system is effective and safe against pituitary adenomas. Careful long-term follow up of the patients is necessary because of long-term anti-tumor effects and delayed adverse events.     

Analysis of Mutations in the Urate Transporter 1 (URAT1) Gene of Japanese Patients with Hypouricemia in Northern Japan and Review of the Literature

Background. Renal hypouricemia is an autosomal recessive disorder resulting from inactivating mutations in the urate transporter 1 (URAT1) encoded by SLC22A12. To date, 10 mutations have been identified and W258X in the URAT1 gene is the predominant cause in middle to southwestern Japan. However, it is still unclear whether there is a regional specific distribution of mutations in northern Japan. In this study, we analyzed mutations in the URAT1 gene of five Japanese patients with renal hypouricemia in northern Japan. Methods. Peripheral blood mononuclear cells were isolated from patients with hypouricemia and healthy control subjects. A mutation analysis of the URAT1 gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. Results. We identified two mutations. These mutations [c.269G>A (R90H) and c.774G>A (W258X)] have been reported in Japanese patients. Two of five patients were homozygotes (W258X), two carried single heterozygous mutations (W258X), and the remaining one was a compound heterozygote (R90H and W258X). Conclusions. Our study suggests that there is no regional different distribution of the URAT1 genetic mutations in Japanese with renal hypouricemia.     

Usefulness of the nadir value of serum prostate-specific antigen measured by an ultrasensitive assay as a predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer

INTRODUCTION: The objective of this study was to determine whether the nadir value of serum prostate-specific antigen (PSA) measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: This study included 127 patients who underwent radical prostatectomy for clinically localized prostate cancer without neoadjuvant hormonal therapy and were pathologically diagnosed as negative for lymph node metastasis. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and the findings were analyzed with respect to several clinicopathological factors. In this series, biochemical recurrence was defined as PSA persistently >0.2 ng/ml. RESULTS: Based on the nadir PSA value, we divided 127 patients into three groups as follows: group A (n=99):or=0.05 ng/ml. The nadir PSA value was significantly associated with preoperative PSA value, but not other conventional clinicopathological prognostic parameters. During the observation period (median 31 months, range 6-75 months), biochemical recurrence occurred in 16 patients, that is, 1 in group A (6.3%), 4 in group B (25.0%), and 11 in group C (91.7%). Multivariate analysis using the Cox proportional hazards regression model indicated that the nadir PSA value was an independent predictor for biochemical recurrence after radical prostatectomy. CONCLUSION: These findings suggest that the nadir serum PSA value measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer, and that careful follow-up should be considered in cases demonstrating a nadir PSA value>0.01 ng/ml because of the significantly higher probability of biochemical recurrence in such cases.     

Orally active neurotrophin-enhancing agent protects against dysfunctions of the peripheral nerves in hyperglycemic animals

Biological substances with neurotrophic activities, such as nerve growth factor (NGF) and monosialoganglioside GM1, have been considered as agents for diabetic peripheral neuropathy. Because recent studies have suggested that decreased availability of these substances might contribute to the pathogenesis of diabetic peripheral neuropathy, some clinical trials of NGF for diabetic peripheral neuropathy have been conducted and have led to mixed conclusions. The major reasons were its limited delivery to the nervous system and adverse effects induced by subcutaneous injection, which was necessary because NGF is a polypeptide. The current study investigates whether an orally active sialic acid derivative, MCC-257, has neuroprotective properties in diabetic peripheral nerves. MCC-257 augmented NGF activity in cultured dorsal root ganglia and PC12 (pheochromocytoma 12) cells. Treatment with MCC-257 elevated NGF levels in the sciatic nerve, accompanied by improvement in nerve conduction velocity in streptozotocin-induced diabetic animals. More importantly, MCC-257 ameliorated small fiber dysfunctions, including thermal hypoalgesia, substance P content, and histopathological innervation in the plantar skin of diabetic animals. Thus, the orally active neurotrophin enhancer provides a new option for the clinical treatment of diabetic peripheral neuropathy.     

Masticatory performance in older subjects with varying degrees of tooth loss

Objectives

The purpose of this study was to establish the factors influencing the masticatory performance of older subjects with varying degrees of tooth loss and associated numbers of posterior occlusal contacts.

Methods

The subjects consisted of 1274 independently living people aged 60 years and over. Individuals with partially or fully edentulous arches without a denture replacement or those having any symptoms related to an oral problem were excluded from the study participants. Masticatory performance, maximal occlusal force and stimulated whole saliva were measured. Subjects were grouped into three categories by posterior occlusal contact, according to the Eichner Index. Group A had contacts in four support zones; group B had one to three zones of contact or contact in the anterior region only; and group C had no support zones at all, although a few teeth could still remain.

Results

The masticatory performance in groups B and C was found to be 81% and 50% of that of group A, respectively. The multiple linear regression analysis showed that in all the groups, occlusal force was significantly associated with masticatory performance. In groups A and B, the number of residual teeth was significantly associated with masticatory performance, whereas in group C, it had no significant relationship with masticatory performance. Salivary flow rate had a significant correlation with masticatory performance only in group C.

Conclusions

Declines in occlusal contact, occlusal force and salivary flow appear to be associated with reduction of masticatory performance in older adults. However, the crucial factors for masticatory performance varied, depending on the phase of occlusal collapse.     

Segmental pulmonary vein antrum isolation using the "large-size" lasso catheter in patients with atrial fibrillation.

BACKGROUND: The limited efficacy and complications of segmental ostial pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have been discussed so, in the present study the feasibility and efficiency of performing segmental pulmonary vein (PV) antrum isolation to treat AF were assessed. METHODS AND RESULTS: A total of 187 patients with drug-refractory AF (paroxysmal 120, persistent 67) underwent segmental PVI guided by circumferential 20-electrode catheters (Lasso). Radiofrequency (RF) current was delivered either at the ostium using a regular Lasso (15-20 mm in diameter, 70 patients: Group 1) or at the antrum using a larger Lasso (25-30 mm in diameter, 117 patients: Group 2). A significantly wider region had to be ablated, with a longer RF application time, to isolate all 4 PVs in Group 2 patients than in Group 1 patients. Although the rate of recurrence of AF after the initial session was equal in both groups, a significantly greater number of patients were free from AF after a mean of 1.4 procedures in Group 2 than in Group 1 (93% vs 76% for paroxysmal AF, 78% vs 48% for persistent AF). CONCLUSIONS: Segmental antral PVI using large-sized Lasso catheters was found to be more effective and safer than ostial PVI for the treatment of AF.