Outcomes of endoscopic treatment for malignant biliary obstruction in patients with surgically altered anatomy: analysis of risk factors for clinical failure

Background To evaluate the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary obstruction (MBO) using short-type double-balloon enteroscope (sDBE) in patients with surgically altered anatomy. Methods A total of 45 patients with surgically altered anatomy underwent ERCP using sDBE for the treatment of MBO between April 2011 and March 2019. We retrospectively evaluated the clinical and technical success (insertion and biliary intervention success), adverse events, and risk factors for clinical failure. Results The scope was successfully inserted in the target site in 82.2% of patients (37/45), and among them, biliary intervention success was achieved in 86.4% (32/37). The overall technical success rate was 71.1% (32/45) and clinical success rate was 68.9% (31/45), with an adverse event rate of 11.1%. In multivariate analysis, the presence of peritoneal dissemination (odds ratio, 7.3; 95% confidence interval, 1.5–43.5, p = 0.02) was as an independent risk factor for clinical failure. The clinical success rate was 38.5% in patients with peritoneal dissemination and 81.3% in those without peritoneal dissemination. Conclusion Endoscopic treatment using sDBE in patients without peritoneal dissemination provided favorable outcomes, and it can be an initial treatment for MBO in patients with surgically altered anatomy. Endoscopic biliary stent placement with endoscopic retrograde cholangiography (ERCP) for the treatment of malignant biliary obstruction (MBO) has been widely accepted as an effective drainage method because it is less invasive and safe and has a high success rate (1–3). However, MBO is treated using percutaneous transhepatic biliary drainage (PTBD) or surgical bypass because of difficulties related to endoscopic access to the bile duct following gastrointestinal reconstruction. However, these methods are associated with marked adverse event (AE) rates [1,2,3]. Recently, balloon-assisted endoscopy (BAE) facilitates ERCP in patients with surgically altered anatomy. As for a double-balloon enteroscope (DBE), a short-type DBE (sDBE) is especially useful because it allows the use of many standard ERCP accessories. The success rates of reaching the target site and ERCP-related interventions associated using these endoscopes range from 73–100% and 85–100%, respectively [4, 5]. We previously reported that the success rate of reaching the target site and biliary intervention was 93.8% and 95.7%, respectively, in patients with benign hepaticojejunostomy (HJ) anastomotic stricture [6]. However, inaccessibility of the target site may occur due to severe postoperative adhesions or a long insertion time (i.e., > 60 min). Furthermore, previous reports have shown that the success rate of BAE in MBO cases was significantly lower than that in benign biliary diseases [7, 8]. Few reports have investigated the outcome of BAE for MBO in patients with surgically altered anatomy. Additionally, the risk factors for clinical failure are not well-established. Thus, we retrospectively evaluated the outcomes of endoscopic treatment for MBO using sDBE in patients with surgically altered anatomy and identified risk factors for clinical failure

Advanced Equipment Development and Clinical Application in Neurorehabilitation for Spinal Cord Injury: Historical Perspectives and Future Directions

Partial to complete paralysis following spinal cord injury (SCI) causes deterioration in health and has severe effects on the ability to perform activities of daily living. Following the discovery of neural plasticity, neurorehabilitation therapies have emerged that aim to reconstruct the motor circuit of the damaged spinal cord. Functional electrical stimulation (FES) has been incorporated into devices that reconstruct purposeful motions in the upper and lower limbs, the most recent of which do not require percutaneous electrode placement surgery and thus enable early rehabilitation after injury. FES-based devices have shown promising results for improving upper limb movement, including gripping and finger function, and for lower limb function such as the ability to stand and walk. FES has also been employed in hybrid cycling and rowing to increase total body fitness. Training using rehabilitation robots is advantageous in terms of consistency of quality and quantity of movements and is particularly applicable to walking training. Initiation of motor reconstruction at the early stage following SCI is likely to advance rapidly in the future, with the combined use of technologies such as regenerative medicine, brain machine interfaces, and rehabilitation robots with FES showing great promise

Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis

Regenerative therapy to replace missing teeth is a critical area of research. Functional bioengineered teeth have been produced by the organ germ method using mouse tooth germ cells. However, these bioengineered teeth are significantly smaller in size and exhibit an abnormal crown shape when compared with natural teeth. The proper sizes and shapes of teeth contribute to their normal function. Therefore, a method is needed to control the morphology of bioengineered teeth. Here, we investigated whether insulin-like growth factor 1 (IGF1) can regulate the sizes and shapes of bioengineered teeth, and assessed underlying mechanisms of such regulation. IGF1 treatment significantly increased the size of bioengineered tooth germs, while preserving normal tooth histology. IGF1-treated bioengineered teeth, which were developed from bioengineered tooth germs in subrenal capsules and jawbones, showed increased sizes and cusp numbers. IGF1 increased the number of fibroblast growth factor (Fgf4)-expressing enamel knots in bioengineered tooth germs and enhanced the proliferation and differentiation of dental epithelial and mesenchymal cells. This study is the first to reveal that IGF1 increases the sizes and cusp numbers of bioengineered teeth via the induction of enamel knot formation, as well as the proliferation and differentiation of dental epithelial and mesenchymal cells

Inflammation-based scoring is a useful prognostic predictor of pulmonary resection for elderly patients with clinical stage I non-small-cell lung cancer

OBJECTIVES: The number of elderly lung cancer patients requiring surgery has been increasing due to the ageing society and less invasive perioperative procedures. Elderly people usually have various comorbidities, but there are few simple and objective tools that can be used to determine prognostic factors for elderly patients with clinical stage I non-small-cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the prognostic factors of surgically treated, over 80-year old patients with clinical stage I NSCLC. METHODS: The preoperative data of 97 over 80-year old patients with clinical stage I NSCLC were collected at Nagasaki University Hospital from 1990 to 2012. As prognostic factors, inflammation-based scoring systems, including the Glasgow Prognostic Score (GPS) determined by serum levels of C-reactive protein and albumin, the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) were evaluated, as well as other clinicopathological factors, including performance status, body mass index, carcinoembryonic antigen, Charlson comorbidity index and type of surgical procedure. RESULTS: The median age was 82 (range, 80-93) years. There were 62 (64.0%) clinical stage IA cases and 35 IB cases. Operations included 64 (66.0%) lobectomies, 15 segmentectomies and 18 wedge resections. The pathological stage was I in 76 (78.4%) patients, II in 12 (12.4%), III in 8 (8.2%) and IV in 1 (1.0%). Twelve (12.4%) patients underwent mediastinal lymph node dissection. Overall survival and disease-specific 5-year survival rates were 55.5 and 70.0%, respectively. The average GPS score was 0.4 (0-2). Diseasespecific 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (74.2%, 53.7%, respectively, P = 0.03). Overall 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (59.7%, 43.1%, respectively, P = 0.005). Both the NLR (median value = 1.9) and the PLR (median value = 117) were not correlated with disease-specific and overall 5-year survival. On multivariate analysis, pathological stage I (P = 0.01) and GPS 0 (P = 0.04, hazard ratio: 2.13, 95% confidence interval 1.036-4.393) were significant prognostic factors. CONCLUSIONS: The preoperative GPS appears to be a useful predictor of overall survival and could be a simple prognostic tool for elderly patients with clinical stage I NSCLC

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered

Phosphatidylinositol 3-kinase-associated protein (PI3KAP)/XB130 crosslinks actin filaments through its actin binding and multimerization properties in vitro and enhances endocytosis in HEK293 cells.

Actin-crosslinking proteins control actin filament networks and bundles and contribute to various cellular functions including regulation of cell migration, cell morphology and endocytosis. Phosphatidylinositol 3-kinase-associated protein (PI3KAP)/XB130 has been reported to be localized to actin filaments (F-actin) and required for cell migration in thyroid carcinoma cells. Here we show a role for PI3KAP/XB130 as an actin-crosslinking protein. First, we found that the carboxyl terminal region of PI3KAP/XB130 containing amino acid residues 830-840 was required and sufficient for localization to F-actin in NIH3T3 cells and this region directly bound to F-actin in vitro. Moreover, actin crosslinking assay revealed that recombinant PI3KAP/XB130 crosslinked F-actin. In general, actin-crosslinking proteins often multimerize to assemble multiple actin-binding sites. We then investigated whether PI3KAP/XB130 could form a multimer. Blue native (BN)-PAGE analysis showed that recombinant PI3KAP/XB130 was detected at 250 kDa-1200 kDa although the molecular mass was approximately 125 kDa, suggesting that PI3KAP/XB130 formed multimers. Furthermore, we found that the amino terminal 40 amino acids were required for this multimerization by co-immunoprecipitation assay in HEK293T cells. Deletion mutants of PI3KAP/XB130 lacking the actin-binding region or the multimerizing region did not crosslink actin filaments, indicating that actin binding and multimerization of PI3KAP/XB130 were necessary to crosslink F-actin. Finally, we examined roles of PI3KAP/XB130 on endocytosis, an actin-related biological process. Overexpression of PI3KAP/XB130 enhanced dextran uptake in human embryonic kidney (HEK) 293 cells. However, most of the cells transfected with the deletion mutant lacking the actin-binding region incorporated dextran to a similar extent as control cells. Taken together, these results demonstrate that PI3KAP/XB130 crosslinks F-actin through both its actin-binding region and multimerizing region and plays an important role in endocytosis

An Adolescent Patient With Idiopathic Pulmonary Arterial Hypertension Weaned Off Intravenous Epoprostenol Following Treatment With Selexipag : A Case Report

Idiopathic pulmonary arterial hypertension (PAH) is a rare, progressive disease affecting the pulmonary arteries. Epoprostenol, a synthetic prostaglandin analog, is the most potent pharmacological treatment modality used in patients with PAH. However, it requires continuous intravenous infusion, which negatively impacts the patient's quality of life and frequently results in complications, such as catheter-related bloodstream infection. We weaned an adolescent female patient off epoprostenol by gradually introducing oral selexipag over a sustained period, following many years of continuous intravenous epoprostenol use alone. Oral selexipag might have an efficacy comparable to epoprostenol in young patients with PAH