Association of sleep‐disordered breathing with decreased cognitive function among patients with dementia

Sleep is known to be essential for proper cognitive functioning. Sleep disturbance, especially respiratory disturbance during sleep, is a risk factor for the development of dementia. However, it is not known whether hypopnoea during sleep is related to severity of cognitive function in patients already diagnosed with dementia. Considering the high prevalence of sleep problems in aged people, it is important to determine if hypopnoea during sleep contributes to dementia. In addition, it would be desirable to develop a feasible method for objectively evaluating sleep in patients with dementia. For this purpose, a simple sleep recorder that employs single or dual bioparameter recording, which is defined as a type‐4 portable monitor, is suitable. In this study, a type‐4 sleep recorder was used to evaluate respiratory function during sleep in 111 patients with dementia, and data suggesting a possible relationship with cognitive function levels were examined. Multivariate logistic regression was used to investigate the association of severity of dementia with sleep‐disordered breathing, age, diabetes, dyslipidaemia and hypertension. It was found that the respiratory disturbance index was associated with severity of cognitive dysfunction in our subjects. Furthermore, patients younger than 80 years were more susceptible to lower cognitive function associated with sleep‐disordered breathing than patients 80 years old or over, because an increase in the respiratory disturbance index was associated with deteriorated cognitive function only in the former age group. These results suggest that proper treatment of sleep apnea is important for the preservation of cognitive function, especially in patients with early‐stage dementia.     

Endoscopic submucosal dissection of squamous cell carcinoma in the upper stomach 5 years after chemoradiotherapy for adenocarcinoma

Primary squamous cell carcinoma is rarely observed, with a reported incidence of 0.04–0.07 % of all gastric cancers. An 81-year-old male underwent chemoradiotherapy for type 1 gastric cancer of the posterior wall of the cardiac region in 2005. The tumor disappeared after 1 year of therapy, following which an area of white epithelium, approximately 30 mm in diameter and continuous with the esophageal mucosa, became visible. Biopsy of the white epithelium indicated normal squamous epithelium. An elevated lesion was subsequently detected in the area of white epithelium on upper gastrointestinal endoscopy during a follow-up examination 5 years after therapy. As a biopsy of the same site indicated squamous cell carcinoma, we performed endoscopic submucosal dissection. Histopathological examination indicated high-grade fibrosis due to radiotherapy and showed a moderately differentiated squamous cell carcinoma invading the scarred portion. We describe a case where the developmental process of a squamous cell carcinoma was observed using endoscopy, including narrow band imaging with magnification. This carcinoma likely originated from squamous metaplasia that developed after chemoradiotherapy was administered for a gastric cancer.     

History and biological significance of GPCR heteromerization in the neuroendocrine system

G protein-coupled receptors (GPCRs) constitute a large family of seven transmembrane proteins that regulate major cellular functions. The important role of GPCRs in the neuroendocrine system is outlined by the great interest of pharmaceutical companies in developing new drugs targeting these receptors. GPCRs exist as monomers, but can also be organized in oligomeric structures composed of either homo- or heteromers. GPCR heteromerization may play an important role in modulating and fine-tuning GPCR function and signaling. The literature reports many examples of GPCR heteromers in vitro raising the question of the physiological relevance of these complexes in tissues. Considerable efforts are currently being directed towards conclusive evidence for the existence of GPCRs heteromers in vivo, a crucial step for the validation of the concept of GPCR heteromerization and future drug development. The present review will give a brief history of GPCR oligomerization and emphasize the importance and physiological relevance of GPCR heteromerization by discussing key examples of GPCR couples.     

Neuroendocrine carcinoma of the stomach: clinicopathological and immunohistochemical evaluation

Neuroendocrine carcinoma (NEC) of the stomach is an uncommon disease. Because of its rarity, the clinicopathological features are unclear, and there is no consensus on the optimal treatment strategy. This study included five consecutive patients with gastric NEC who underwent surgery from July 2001 to August 2011. Clinical presentation, tumor location, tumor morphology and size, pathology and immunohistochemistry results, and treatment outcome were analyzed retrospectively and discussed. The study cohort of four men and one woman ranged in age from 52 to 84 years, with a median age of 72 years. Positive rates of neuroendocrine markers were 40 % for chromogranin A, 60 % for synaptophysin, 60 % for CD56, 40 % for neuron-specific enolase, and 100 % for p53 protein. Median number of lymph node metastases per patient was 10, with severe lymphatic and venous infiltration, and high Ki-67 labeling index (60–90 %) reported for all patients. Median tumor size was 6 cm. Stage IV disease was diagnosed in three patients; the other two patients showed stage IIIA tumors. After a mean follow-up of 29.8 months, two of the five patients had died of the disease. Although rare, gastric NECs deserve particular attention because of their strong malignant potential associated with an extremely poor prognosis. Such carcinomas demand an aggressive surgical approach followed by chemotherapy and multimodality adjuvant therapy.     

Impact of official technical training for urologists on the efficacy of shock wave lithotripsy

To evaluate the efficacy of company-initiated training of urologists on shock wave lithotripsy (SWL) treatment results, we retrospectively assessed 602 patients who underwent SWL in Nagoya City University Hospital between January 2004 and June 2011 using Lithotripter S (Dornier MedTech, Japan). Training—provided by a training specialist of the company in June 2010—focused on the targeting of renal and proximal ureter stones with a combination of radiography and ultrasonography (US). The stretcher wedges were positioned in the semi-prone position or the semi-supine position for middle and distal ureter stones, respectively. Success rates between 519 pre-training treatments and 83 post-training treatments were compared. Patient age and stone location, burden, number, and composition did not significantly differ between pre- and post-training. Training improved the overall success rate from 66.3 to 87.2 % (P < 0.0001). The mean number of SWL treatments decreased from 1.8 ± 1.8 to 1.4 ± 1.3 (P = 0.01). The first SWL treatment success rate increased from 67.1 to 83.7 % (P = 0.002), and the need for multiple treatments decreased. The frequency of detection of renal and proximal ureter stones by both radiography and US increased from 10.5 % before training to 58.2 % after training (P < 0.0001). Significant factors for successful SWL were determined to be training and prone position for distal ureter stones by multivariate analysis and ultrasonic detection for renal and proximal ureter stones by univariate analysis. Skills in targeting stones using ultrasonography and selecting the proper therapeutic position are essential for improving the success rate of stone removal.     

Optimal follow-up time to determine the sustained virological response in patients with chronic hepatitis C receiving pegylated-interferon and ribavirin

Background and Aim: This study evaluated whether the assessment of hepatitis C virus (HCV)‐RNA at 12 weeks (FW+12) post‐treatment follow‐up was as applicable as FW+24 to evaluate sustained virological response (SVR) using the highly sensitive real‐time polymerase chain reaction (PCR) HCV assay. Methods and Results: Two hundred and twenty‐two patients with chronic hepatitis C were included in this study. Pegylated interferon (Peg‐IFN) and ribavirin were administered for 24–72 weeks based on the genotype and viral load. Serum HCV‐RNA was measured using real‐time PCR at pretreatment, the end of treatment, FW+4, FW+8, FW+12, FW+16, FW+20 and FW+24. Two hundred patients had a virological response at the end of treatment. One hundred and forty‐eight of 200 (74.0%) patients with a virological response at the end of treatment had an SVR at the FW+24. The positive predictive value (PPV) to identify patients with SVR at FW+4, FW+8, FW+12 was 87.1, 96.1, 98.0%, respectively. The viral load showed a reversion to the basal level as early as 8 weeks in relapse patients. There were only three patients who relapsed after FW+12 and all three of these patients were females with genotype Ib and a high viral load. Conclusion: The assessment of serum HCV‐RNA FW+12, using the highly sensitive real‐time PCR assay, is almost as effective as FW+24 to predict SVR. However, there are false negatives in female patients with a high viral load of genotype Ib when the SVR is predicted by FW+12. The current standard with FW+24 is reasonable, but the assessment of serum HCV‐RNA FW+12 may be effective in most patients.