Efficacy of mosapride citrate in proximal gastric accommodation and gastrointestinal motility in healthy volunteers: a double-blind placebo-controlled ultrasonographic study

Background  

Mosapride citrate, a 5-hydroxytryptamine-4 receptor agonist, enhances antral contractions and gastric emptying, but its effects on proximal gastric accommodation and gastroduodenal motility have not been fully studied. The aim of the present study was to clarify the effects of mosapride citrate on proximal gastric accommodation and gastroduodenal motility in healthy volunteers, using ultrasonography.     

Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan

Background

There have been few epidemiological studies on gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Japan.

Methods

We examined the epidemiology of GEP-NETs [pancreatic endocrine tumors (PETs) and gastrointestinal neuroendocrine tumors (GI-NETs)] in Japan in 2005 using a nationwide stratified random sampling method.

Results

A total of 2,845 individuals received treatment for PETs. Prevalence was estimated as 2.23/100,000 with an annual onset incidence of 1.01/100,000. Non-functioning tumor (NF)-PET constituted 47.4%, followed by insulinoma (38.2%) and gastrinoma (7.9%). Distant metastases were reported in 21% patients with NF-PETs and occurred more frequently as tumor size increased (>2 cm). Multiple endocrine neoplasia type 1 (MEN-1) was detected in 10% of PETs but only in 6.1% of NF-PETs. NF-PETs were detected incidentally by physical examination in 24% patients. In 2005, an estimated 4,406 patients received treatment for GI-NETs. Prevalence was estimated as 3.45/100,000, with an annual onset incidence of 2.10/100,000. The locations of GI-NETs varied: foregut, 30.4%; midgut, 9.6%; and hindgut, 60.0%. Distant metastases were observed in 6%. Lymph node metastases occurred more frequently as tumor size increased (>1 cm). The frequency of MEN-1 complications was 1%. Physical examination revealed GI-NETs in 44% patients. The frequency of symptomatic GI-NETs was 3.4%. Interestingly, 77.1% of patients with foregut GI-NETs had type A gastritis.

Conclusion

Our results show there are large differences in GEP-NETs between Japan and Western nations, primarily due to differences in the presence of MEN-1 in NF-PETs and the location, symptomatic status, and prevalence of malignancy in GI-NETs.     

Bezafibrate for the treatment of primary sclerosing cholangitis

Background

It is known that bezafibrate decreases serum alkaline phosphatase (ALP) in patients with hyperlipidemia, and the efficacy of this drug for the treatment of primary biliary cirrhosis has been confirmed. However, there has been little evidence of its efficacy for the treatment of primary sclerosing cholangitis (PSC).

Methods

Bezafibrate (400 mg/day) was orally administered to 7 consecutive patients with PSC, and we analyzed their clinical features and the drug efficacy in terms of the effect on hepatobiliary enzymes, including ALP, gamma-glutamyl transpeptidase (γ-GTP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) after 6 months. The latest hepatobiliary enzyme levels were also evaluated.

Results

In 3 patients (effective group), the levels of all hepatobiliary enzymes had decreased after 6 months. Mean ALP had decreased to approximately 40% of the baseline in this group. The efficacy of bezafibrate was observed for a long period (range, 8–27 months) in these 3 patients. There seemed to be no definite association between the efficacy of bezafibrate and the clinical features in the short term.

Conclusions

This study showed that bezafibrate could lower the levels of hepatobiliary enzymes in about half of a cohort of patients with PSC.     

Timing of Resection for Synchronous Liver Metastases from Colorectal Cancer

Background  

This study aimed to compare the surgical outcome and long-term survival between simultaneous and delayed resection of liver metastases from colorectal cancer (LM), and to identify the factors influencing hepatic disease-free survival in patients with synchronous LM.     

Levels of Transferrin in Bronchoalveolar Lavage Fluid in Sarcoidosis

There has been only one report showing high levels of transferrin (Tf) in bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis. This study was designed to assess the levels of Tf in both BALF and serum and to examine the relationship between the levels of Tf and other disease markers in sarcoidosis. Subjects were 64 sarcoidosis and 10 healthy controls. Tf in BALF and serum was measured by nephelometric assay. Median Tf levels in BALF from sarcoidosis was 0.70 (range, 0.00–3.97) mg/dl, which was significantly higher compared with controls (0.36 (range, 0.00–1.02) mg/dl; p = 0.005). In contrast, median Tf levels in serum from sarcoidosis was 258 (range, 171–383) mg/dl, which was significantly lower compared with controls (322 (range, 234–356) mg/dl; p = 0.003). Tf levels in BALF were significantly correlated with both the percentage of lymphocytes (r = 0.617, p = 0.001) and serum angiotensin-converting enzyme activity (r = 0.363, p = 0.003) and serum soluble interleukin-2 receptor (r = 0.450, p = 0.001) in sarcoidosis. Levels of Tf in BALF from patients with sarcoidosis were not influenced by smoking status. The levels of Tf in sarcoidosis are high in BALF, but low in serum. Increased levels of Tf in BALF may reflect the disease activity.     

A case of giant esophageal leiomyoma successfully resected by endoscopic submucosal dissection followed by retrieval via laparotomy

A 30-year-old woman with chest discomfort at swallowing and occasional vomiting was referred to our department with a diagnosis of esophageal submucosal tumor. CT visualized a mass 70 mm in diameter in the middle esophagus. Esophagogastroduodenoscopy revealed a pedunculated submucosal tumor, and endoscopic resection was considered. As the size of the tumor was so large, retrieval of the resected specimen via the stomach following incision, laparotomy was planned. En bloc resection by endoscopic submucosal dissection with a Hook-knife was performed. Retrieval of the resected specimen was carried out as planned. The specimen, which was 53×48×43mm in size with a distinct margin, was diagnosed as leiomyoma derived from the muscularis mucosae histologically. Her postprocedural course was uneventful. Endoscopic resection can be chosen when an esophageal submucosal tumor is pedunculated with abundant mobility, making it possible to avoid invasive surgery.     

Glomerular Density in Renal Biopsy Specimens Predicts the Long-Term Prognosis of IgA Nephropathy

Background and objectives: An early histopathologic predictor of the renal prognosis, before the occurrence of advanced glomerular sclerosis/interstitial fibrosis and/or apparent renal dysfunction, remains to be established in IgA nephropathy (IgAN). This study aimed to determine whether the glomerular density (GD; nonsclerotic glomerular number per renal cortical area) of biopsy specimens obtained at an early stage of IgAN could predict the long-term renal outcome.Design, setting, participants, & measurements: The predictive value of the factors at biopsy, including the GD, on the renal outcome was retrospectively analyzed for 98 patients who had IgAN with an estimated GFR of ≥60 ml/min per 1.73 m² at biopsy (87 ml/min per 1.73 m² on average).Results: The individual value of GD in biopsy ranged from 1.2 to 8.1/mm² (i.e., approximately a seven-fold variation), and the GD showed a close inverse correlation with mean glomerular volume. Among the various clinicopathologic factors involved, both a cellular/fibrocellular crescent and the GD were found to be significant predictors of progression in multivariate analyses. A low GD in the biopsy specimens was frequently associated with a steeper slope of the renal function and a synergistically enhanced risk for progression with the presence of cellular/fibrocellular crescent. The renal function, proteinuria, degrees of glomerulosclerosis, and interstitial fibrosis at biopsy were not independent predictors of the prognosis in these patients.Conclusions: A strong predictive relationship of low GD with progression observed in this study suggests that GD may serve as an early histopathologic marker of long-term renal prognosis in IgAN.The outcome of IgA nephropathy (IgAN) is highly variable among individuals (1–4). Some patients maintain only isolated urinary symptoms for many years, whereas other patients progress to ESRD. Previous studies have consistently identified various clinicopathologic parameters at the time of diagnosis, especially heavy proteinuria, reduced renal function, advanced glomerular sclerosis, or tubulointerstitial fibrosis, as independent risk factors for progression (4–7); however, these findings characterize already advanced renal injury rather than reflect the progression rate of renal diseases. The factors that may allow prediction of progression in early stage of IgAN remain to be fully elucidated.We recently performed a study using pairs of serial biopsy specimens from 18 patients with progressive IgAN (8). In these patients, renal biopsies were performed both before and after the establishment of impaired renal function. We found a low glomerular density (GD; the number of nonsclerotic glomeruli per renal cortical area) in the first biopsy to be associated with both the already enlarged glomeruli and an increased susceptibility to subsequent renal scarring and a more rapid progression. A high GD in the first biopsy was associated with a relatively slow progression despite a large increase in the glomerular size in the second biopsy. These results were consistent with the currently proposed concept that kidneys with a reduced nephron number, presumably having less of a functional reserve, may cause glomerular enlargement, thereby becoming more susceptible to subsequent renal injury and functional decline (9–11). We therefore hypothesized that the GD in the early stage of “potentially progressive” renal diseases, such as IgAN, can predict subsequent renal adaptation and/or scarring and thus serve as an early marker of renal prognosis.By analyzing a larger number of patients, this study aimed to clarify the relationship between GD and the long-term renal outcome of patients with IgAN and without any apparent renal dysfunction at the time of biopsy. In addition to the patients who showed a progressive loss of renal function, this study included patients whose renal function had been stable for a long time.