A case of pulmonary arterial hypertension complicated by anti-neutrophil cytoplasmic antibody-associated vasculitis and systemic sclerosis

Pulmonary arterial hypertension (PAH) is a rare complication of ANCA-associated vasculitis (AAV). We report a 37-year-old man with PAH complicated by both AAV and SSc who presented with dyspnea, cardiac enlargement, positive myeloperoxidase (MPO)-ANCA, anti-centromere antibodies, proteinuria, and urinary casts. Elevated pulmonary arterial pressure (58/22/34 mmHg) and low PAWP (2 mmHg) were confirmed by right heart catheterization. Treatment with glucocorticoids (GC) decreased urinary protein and serum MPO-ANCA; however, PAH did not respond to GC. Therefore, a combination of beraprost, bosentan, and tadalafil was needed. The differences in responses to GC suggest that the pathophysiology of nephropathy is different from that of PAH. We considered that nephropathy was associated with AAV but that PAH was associated with SSc in the present case. We discuss the pathophysiology and treatment response of PAH complicated by AAV, referring to nine past cases

Endoscopic Resection of Zenker's Diverticulum

We report an endoscopically assisted total diverticulectomy for Zenker's diverticulum. Skin incisions were made at the anterior axillary line, the center of the sternum, and the neck as portals for endoscopical instruments. The skin was retracted with hooks which provided an excellent view of the working space. The diverticulum was fully exposed and resected by using a multifire endoscopic stapler. This approach is minimally invasive in comparison with the conventional open cervical approach

Somatic chromosomal translocation between Ewsr1 and Fli1 loci leads to dilated cardiomyopathy in a mouse model

A mouse model that recapitulates the human Ewing's sarcoma-specific chromosomal translocation was generated utilizing the Cre/loxP-mediated recombination technique. A cross between Ewsr1-loxP and Fli1-loxP mice and expression of ubiquitous Cre recombinase induced a specific translocation between Ewsr1 and Fli1 loci in systemic organs of both adult mice and embryos. As a result Ewsr1-Fli1 fusion transcripts were expressed, suggesting a functional Ews-Fli1 protein might be synthesized in vivo. However, by two years of age, none of the Ewsr1-loxP/Fli1-loxP/CAG-Cre (EFCC) mice developed any malignancies, including Ewing-like small round cell sarcoma. Unexpectedly, all the EFCC mice suffered from dilated cardiomyopathy and died of chronic cardiac failure. Genetic recombination between Ewsr1 and Fli1 was confirmed in the myocardial tissue and apoptotic cell death of cardiac myocytes was observed at significantly higher frequency in EFCC mice. Moreover, expression of Ews-Fli1 in the cultured cardiac myocytes induced apoptosis. Collectively, these results indicated that ectopic expression of the Ews-Fli1 oncogene stimulated apoptotic signals, and suggested an important relationship between oncogenic signals and cellular context in the cell-of-origin of Ewing's sarcoma

無症候性腎機能障害が膵頭十二指腸切除術後臨床経過に及ぼす影響

BACKGROUND: Although recent large-scale clinical studies have shown that preoperative renal insufficiency is associated with increased risk of postoperative complications after pancreatoduodenectomy (PD), it is unknown whether asymptomatic renal dysfunction has an impact on postoperative course after PD. METHODS: Two hundred and fifty-four patients who underwent PD between 2007 and 2013 were enrolled. Renal function was evaluated by the preoperative estimated glomerular filtration rate (eGFR). Patients were divided into two groups according to the cutoff value of 55 of eGFR. RESULTS: Thirty-five patients were classified as the low eGFR group, while 219 were classified as the normal group. There were differences between groups in age, comorbidity and pancreatic texture. The incidence of overall postoperative complication, grade B/C pancreatic fistula and severe complication in the low eGFR group was significantly higher than that in the normal group. Multivariate analysis identified low eGFR as an independent risk factor for severe postoperative complications and grade B/C pancreatic fistula after PD. However, there were no differences in mortality and survival between the low and normal eGFR groups. CONCLUSIONS: We have demonstrated for the first time that preoperative asymptomatic renal dysfunction may be a significant risk factor for severe morbidity and clinically relevant pancreatic fistula after PD.博士（医学）・乙第1394号・平成29年3月15日© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.This is the peer reviewed version of the following article: http://dx.doi.org/10.1002/jhbp.286, which has been published in final form at http://dx.doi.org/10.1002/jhbp.286. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving

化学療法を施行した膵癌患者に対する喫煙の影響

OBJECTIVE: Smoking may affect pharmacokinetics of chemotherapeutic agents and hemodynamics of the smokers, thereby influencing adverse events and efficacy of chemotherapy in patients with pancreatic cancer (PC). The aim of this study was to clarify how smoking totally affected patients with PC receiving current chemotherapy. METHODS: We evaluated the impact of smoking status on the performance of chemotherapy and survival in 262 patients with PC including 158 resectable and 104 unresectable PC. RESULTS: There were more male and younger patients in current smokers than in nonsmokers. In unresectable PC, current smokers had more metastatic tumors than locally advanced tumors compared with nonsmokers. In current smokers receiving chemotherapy, the baseline white blood cell count, neutrophil count, and hemoglobin concentration were significantly higher in current smokers than in nonsmokers. Furthermore, grades 3 to 4 neutropenia was observed more often in nonsmokers than smokers. On the other hand, the performance and efficacy of the planned adjuvant chemotherapy were similar between smokers and nonsmokers. More importantly, there was no significant difference in overall prognosis between smokers and nonsmokers receiving chemotherapy. CONCLUSIONS: Smoking status has no significant impact on the efficacy of current chemotherapy for both resectable and unresectable PC.博士（医学）・乙第1393号・平成29年3月15日Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.This is a non-final version of an article published in final form in "http://dx.doi.org/10.1097/MPA.0000000000000395

Nagasaki Schizophrenia Study: Relationship Between Ultralong-term Outcome (after 28 years) and Duration of Untreated Psychosis

Objective: Numerous studies have shown a relationship between the duration of untreated psychosis (DUP) in schizophrenia and short-termoutcome. However, few studies have investigated the relationships between DUP and the medium-term and long-term outcomes. Furthermore,we are unaware of any reports regarding the relationship between DUP and the ultralong-term outcome. This study aimed to investigate therelationship between DUP and ultralong-term outcome at 28 years in patients with schizophrenia.Method: Patients with schizophrenia completed an interview survey 28 years after their initial psychiatric examination during the period 1979-1980. It was possible to conduct the survey using suitable assessment scales in 31 patients in whom DUP was confirmed. These patients weredivided into a short DUP group and a long DUP group on the basis of the median DUP, and the outcomes of these two groups were compared.Results: Longer DUP correlated significantly with poorer symptomatic outcome; degree of social adjustment; and, global functioning. Multiplelinear regression analysis found no changes in these results even after controlling for various factors, including gender, age at onset, mode ofonset, diagnostic subtype, and premorbid adjustment.Conclusion: DUP adversely affected ultralong-term outcome of schizophrenia after 28 years. This finding supports the need to establish asystem to enable early detection and appropriate intervention for patients with schizophrenia to reduce the risk of a deleterious outcome aftermore than 25 years

Epidemiological survey of first-episode psychosis in Nagasaki, Japan: Is the incidence rate of schizophrenia changing?

The Determinants of Outcome of Severe Mental Disorders (DOSMeD) study, a global epidemiological study led by the World Health Organization, reported the annual incidence rate of schizophrenia from 1979 to 1980. In 2011, approximately 30 years later, we conducted a large-scale epidemiological study to investigate the incidence rate of first-episode schizophrenia in Nagasaki using the same method as the DOSMeD study. A telephone survey was conducted by researchers daily at 52 psychiatric hospitals, clinics, and institutes in Nagasaki. When a subject was confirmed, the researcher visited the medical facility in person to evaluate the patient’s symptoms. Of 441,706 people in Nagasaki City, 131 people were surveyed in the way, resulting in the diagnosis of psychosis in 25 patients, 20 of whom were determined to have schizophrenia. These data were used to calculate the incidence rates of psychosis (1.00 per 10,000 population; 95% confidence interval [CI], 0.54-1.46) and schizophrenia (0.80 per 10,000 population; 95% CI, 0.38-1.21). The 95% CI for the incidence rate of psychosis did not include the incidence rate for psychosis (broad definition) reported in the DOSMeD study (2.02). However, the 95% CI for the incidence rate of schizophrenia did include the incidence rate for schizophrenia (restrictive definition) reported in the DOSMeD study (1.01). Although the incidence rate of psychosis appeared to be decreasing, no significant change was found in the incidence rate of schizophrenia, comparing the present findings with those of the survey conducted 30 years ago. The incidence rate of schizophrenia is said to vary with changes in gender differences, racial differences, urbanization, and immigration; we therefore considered this possibility. In the future, it is necessary to carry out longer-term surveys covering multiple cities using the same methods

The renin–angiotensin system promotes arrhythmogenic substrates and lethal arrhythmias in mice with non-ischaemic cardiomyopathy

[Aims]The progression of pathological left ventricular remodelling leads to cardiac dysfunction and contributes to the occurrence of malignant arrhythmias and sudden cardiac death. The underlying molecular mechanisms remain unclear, however. Our aim was to examine the role of the renin–angiotensin system (RAS) in the mechanism underlying arrhythmogenic cardiac remodelling using a transgenic mouse expressing a cardiac-specific dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). This mouse model exhibits progressive cardiac dysfunction leading to lethal arrhythmias. [Methods and results]Subcutaneous administration of aliskiren, a direct renin inhibitor, significantly suppressed the progression of pathological cardiac remodelling and improved survival among dnNRSF-Tg mice while reducing arrhythmogenicity. Genetic deletion of the angiotensin type 1a receptor (AT1aR) similarly suppressed cardiac remodelling and sudden death. In optical mapping analyses, spontaneous ventricular tachycardia (VT) and fibrillation (VF) initiated by breakthrough-type excitations originating from focal activation sites and maintained by functional re-entry were observed in dnNRSF-Tg hearts. Under constant pacing, dnNRSF-Tg hearts exhibited markedly slowed conduction velocity, which likely contributes to the arrhythmogenic substrate. Aliskiren treatment increased conduction velocity and reduced the incidence of sustained VT. These effects were associated with suppression of cardiac fibrosis and restoration of connexin 43 expression in dnNRSF-Tg ventricles. [Conclusion]Renin inhibition or genetic deletion of AT1aR suppresses pathological cardiac remodelling that leads to the generation of substrates maintaining VT/VF and reduces the occurrence of sudden death in dnNRSF-Tg mice. These findings demonstrate the significant contribution of RAS activation to the progression of arrhythmogenic substrates