Objective A 50-100-mg rectal dose of nonsteroidal anti-inflammatory drugs (NSAIDs; diclofenac or indomethacin) has been shown to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, this is higher than the recommended 25-mg dose that is commonly administered to Japanese patients. The objective of this study was to evaluate the safety and efficacy of 25-mg rectal dose of diclofenac in preventing PEP.

Methods Between January 2016 and March 2017, a total of 147 patients underwent ERCP with or without the rectal administration of diclofenac (25 mg) 20 min before the procedure. A retrospective analysis was conducted to evaluate the efficacy and safety of this dose in preventing PEP.

Results Thirteen patients (8.8%) developed PEP: 3 patients (4.1%) in the diclofenac group and 10 (13.7%) in the control group (p=0.0460). After ERCP, there were no cases of gastrointestinal hemorrhage, ulceration, acute renal failure, or death. A multivariate logistic regression analysis revealed that the non-administration of rectal diclofenac was a risk factor for PEP (odds ratio=3.530; 95% confidence interval=1.017-16.35; p=0.0468).

Conclusions A 25-mg rectal dose of diclofenac might prevent PEP.

Objective The progress of non-anticoagulated patients with atrial fibrillation (AF) undergoing hemodialysis has not been determined. Using data from the RAKUEN (Registry of Atrial fibrillation in chronic Kidney disease Under hEmodialysis from Niigata) study, we examined the clinical characteristics and outcomes among hemodialysis patients with AF who were not receiving a vitamin K antagonist (VKA).

Methods and Results Forty-three of 423 patients undergoing hemodialysis (-10%) were prescribed a VKA. The remaining 380 patients (age 64.8±12.8 years, male 70%) were enrolled in the present study. During a mean observation period of 36 months, AF (n=55) was independently associated with all-cause death (hazard ratio, 1.82; 95% confidence interval, 1.12-2.94; p=0.014), but was not associated with ischemic stroke (hazard ratio, 1.91; 95% confidence interval, 0.74-4.92; p=0.177) and major bleeding (hazard ratio, 1.80; 95% confidence interval, 0.80-4.08; p=0.150). The crude incidence rates of all-cause death and ischemic stroke in the AF patients were 15.75 (2.5-fold higher compared to the non-AF patients) and 3.63 (1.7-fold higher compared to the non-AF patients) per 100 person-years, respectively.

Conclusion A great impact on death, but not ischemic stroke, was observed in non-anticoagulated hemodialysis patients with AF in comparison to those without AF from the analysis of the RAKUEN study.

Objective Our aim was to examine the clinical characteristics and phenotype of lipodystrophy of six diabetic Japanese women with partial lipodystrophy (PL) who received a genetic analysis at a diabetic outpatient clinic.

Methods We screened for PL using dual energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI) among patients who had a reduced peripheral skinfold thickness at the diabetic outpatient clinic of Kusatsu General Hospital between August 2003 and August 2013. We performed a mutation analysis of candidate genes, including LMNA and PPARG, in two patients with PL and whole-exome sequencing in four patients with PL.

Results We identified 15 patients with PL and performed a genetic analysis in 6 of them. They had no mutations in candidate genes known to be associated with familial partial lipodystrophy (FPLD). They all had near-complete loss of subcutaneous fat, particularly in the antero-lateral and posterior thigh region and the calf region. As almost all patients were characterized by fat loss in the lower limbs with abdominal fat accumulation, a high rate of positivity for a family history, diabetes, and an unknown genetic cause, we suspected they might have FPLD1. Some patients have shown relatively severe insulin resistance, while others have shown insulin deficiency. Four and one had severe atherosclerosis and liver cirrhosis, probably due to nonalcoholic steatohepatitis, respectively.

Conclusion Almost all patients with PL identified in a diabetic outpatient clinic had subcutaneous fat loss in the lower limbs with excess truncal fat and might have had FPLD1.

Objective The early detection and treatment of chronic obstructive pulmonary disease (COPD) requires comprehensive follow-up over a long period. The aim of this study was to determine the effects of a comprehensive long-term intervention system developed by the COPD Task Force for a rural city in Japan during a 7-year period.

Methods This prospective, community-based longitudinal study encompassed 2006-2013 in Matsuura City, Japan. Primary and secondary screenings were performed for the early diagnosis and treatment of COPD. Individuals diagnosed with COPD were managed by the COPD Task Force's comprehensive early intervention system. The outcomes of interest were the rate of continuous follow-up after the diagnosis of COPD, the smoking cessation rate, and changes in the pulmonary function during a 7-year period.

Subjects The study included 8,878 residents of 50-89 years of age who resided in Matsuura in 2006.

Results In total, 140 participants received definitive diagnoses of COPD in 2006. After 7 years of intervention, 34 patients withdrew; 78 (74%) patients continued with treatment in our intervention system. The rate of smoking cessation was significantly increased in the intervention group (from 30% to 68%; p<0.01) over the 7-year period. The change in forced expiratory volume in 1 second (FEV₁) was -23.2 mL/year.

Conclusion Our systematic longitudinal intervention system during a 7-year period led to high rates of follow-up and smoking cessation. Furthermore, our system may be able to prevent the decline of FEV₁ in COPD patients. This intervention system may be effective in rural cities with few respiratory physicians.

Objective This study attempted to clarify the current status of female dystrophinopathy carriers, including the numbers of patients, the status of genetic screening, the status of counseling, physicians' understanding, and barriers to registration.

Methods We sent out questionnaires to 402 physicians registered in the Remudy dystrophinopathy registry. The total number of responses received was 130 (response rate: 32%).

Result In total, 1,212 cases of Duchenne muscular dystrophy, 365 cases of Becker muscular dystrophy, and 132 cases of female dystrophinopathy with a confirmed genetic mutation were encountered, and genetic testing was performed in the mother in 137, 23, and 12 cases, respectively. With respect to the risk of the onset of health problems, 25% of physicians always explained, 29% usually explained, 29% sometimes explained, and 13% never explained the risk to the mothers and female siblings of dystrophinopathy patients. The most common reason for not explaining the risk was a lack of knowledge/information. Thirty-five percent were familiar with the guidelines for testing the heart function of carriers.

Conclusion Fewer mothers of dystrophinopathy patients have undergone genetic testing in Japan than in other countries. A significant portion of doctors did not explain the risks of health problems due to a lack of knowledge. We hope this survey will lead to an increased discussion of female dystrophinopathy patients.

A 50-year-old man who presented with a fever and epigastralgia was diagnosed to have esophageal carcinoma which was identified as poorly differentiated adenocarcinoma producing alpha-fetoprotein (AFP) with Barrett's esophagus. Computed tomography revealed multiple liver metastases and lymph node metastases surrounding the stomach. We first performed chemotherapy for the systemic lesions and proton beam therapy for the local control of lesions without complete remission and we were able to successfully control the frequently recurring lesions by proton beam therapy, cryotherapy and chemotherapy. A complete response has been maintained for 16 months and the overall survival time is 4 years and 2 months. Proton beam therapy for primary esophageal cancer and metastatic lesions was thus found to be an effective therapeutic option for such cases.

Gastric arteriovenous malformation (AVM) is an uncommon cause of upper gastrointestinal bleeding, and the endoscopic findings are unclear. We herein describe a case of gastric AVM in a 28-year-old man. Esophagogastroduodenoscopy showed a Dieulafoy lesion surrounded by a red mucosa with a sharp margin, which implied blood vessel malformation. Computed tomography angiography and conventional angiography revealed aggregated vessels on the greater curvature. Partial gastrectomy was performed, with no recurrent bleeding postoperatively. The histopathological diagnosis was AVM. We conclude that gastric AVM should be considered in the differential diagnosis of patients who present with a Dieulafoy lesion surrounded by a red mucosa.

A 69-year-old Japanese woman presented to our hospital for the further investigation of an esophageal subepithelial tumor. A diagnosis of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was made by an endoscopic biopsy. The patient had no involvement other than the esophagus. The tumor was resected using endoscopic submucosal dissection. Lymphoma recurrence has not been documented in the 57 months since resection. This case suggests that although a detailed preoperative evaluation is required to determine the extent of tumor, endoscopic resection may be an option for the long-term disease control of MALT lymphoma of the esophagus.

A 79-year-old woman without any cerebral hernia symptoms was hospitalized with hyponatremia. After syndrome of inappropriate antidiuretic hormone induced by drugs was diagnosed and water restriction implemented, the patient became comatose during overcorrection caused by the generation of a large volume of electrolyte-free urine. Once the serum sodium concentration was immediately relowered by the administration of desmopressin and 5% glucose solution, the patient's level of consciousness improved dramatically without osmotic demyelination syndrome (ODS) developing. This outcome suggests that, similar to the findings in rat models, relowering the serum sodium concentration as early as possible to counter a disturbance of consciousness during the overcorrection of hyponatremia prevents ODS.

Type B insulin resistance syndrome is a rare autoimmune disease and no effective therapy has yet been established. On the other hand, it is known that Saibokuto, one type of Japanese Kampo medicine, may have beneficial effects on various symptoms associated with this disease and it is therefore occasionally prescribed for various immune disorders. We herein describe a case of type B insulin resistance syndrome in which anti-insulin receptor antibody disappeared and the patient's glycemic control markedly improved after the administration of Saibokuto. At first, we administered various anti-oral diabetic drugs and insulin therapy, but the patient's glycemic control became further aggravated. In addition, Helicobacter pylori eradication therapy was not effective, although its benefit has been reported. Interestingly, after the patient started taking Saibokuto, her glycemic control markedly improved. In addition, the patient's plasma insulin levels markedly decreased and anti-insulin receptor antibody became negative after taking Saibokuto. Taken together, there is a possibility that Saibokuto may one of the options for type B insulin resistance syndrome therapy.

Heparin is commonly used to prevent clotting; however, severe hypersensitivity reactions during vascular access (VA) placement are rarely but occasionally reported. A 49-year-old man experienced a heparin-induced hypersensitivity reaction during VA placement. Severe side effects may occur even while placing the VA; therefore, we reconsidered the routine use of heparin, as the side effects are unpredictable. Physicians should be aware of the risk of heparin-induced hypersensitivity and be ready to effectively manage it during VA placement.

Invasive tracheobronchial aspergillosis (ITBA), a rare form of invasive pulmonary Aspergillus infection (IPA), is predominantly confined to the tracheobronchial tree. We herein report a case of ITBA with severe necrotic pseudomembrane in a 57-year-old woman with fulminant hepatitis and hemophagocytic syndrome. Bronchoscopic findings revealed a widespread pseudomembranous formation of the trachea and bronchi. Aspergillus fumigatus was cultured from bronchial lavage fluid, and the histological findings of an endobronchial biopsy revealed necrosis and invasive hyphae. Although she responded to antifungal treatment, she ultimately died of a septic shock with Burkholderia cepacia 57 days after admission.

A 63-year-old woman with pulmonary adenocarcinoma (stage IIIB) that was positive for an epidermal growth factor receptor (EGFR) mutation and an anaplastic lymphoma kinase (ALK) rearrangement was treated with erlotinib as the first-line treatment, resulting in a stable disease. Due to skin rashes, fatigue and anorexia, erlotinib was suspended on erlotinib day 44. Alectinib was administered as the second-line treatment, exhibiting a partial response. On alectinib day 56, drug-induced lung injury forced suspension of alectinib, which was cured with corticosteroid therapy. ALK-tyrosine kinase inhibitors may be more effective for patients positive for both EGFR mutation and ALK rearrangement than other agents.

Stereotactic radiosurgery (SRS) using the Gamma Knife (GK) is now being increasingly utilized for the treatment of brain metastases. However, there are a few reported cases of SRS-induced brain neoplasms. We herein report the case of a Japanese woman with metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor (EGFR)-mutations who was treated four times with a GK for brain metastases. She developed glioblastoma 5.7 years after the initial GK surgery. Radiation-induced secondary neoplasms generally appear after a latency period of several years. Advances in cancer therapy have improved the survival of patients with NSCLC, providing enough time for secondary neoplasms to appear after SRS.

Chronic pulmonary aspergillosis is a major cause of life-threatening hemoptysis. In symptomatic patients with simple aspergillomas, surgery is the main therapeutic method for preventing or treating life-threatening hemoptysis. However, the risks of both death and complications are higher in chronic cavitary pulmonary aspergillosis than in simple aspergilloma. We herein report two patients with persistent moderate hemoptysis due to chronic cavitary pulmonary aspergillosis who were not indicated for surgery, but were able to undergo successful long-term management with bronchial occlusion using silicone spigots. In diseases with a high recurrence rate of hemoptysis, the continuous placement of silicone spigots might therefore be effective to prevent rebleeding.

Paraneoplastic pemphigus (PNP) is a severe autoimmune blistering disease associated with an underlying malignancy, and its prognosis is poor. We herein report the first patient with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL)-associated PNP successfully treated with the Bruton's tyrosine kinase inhibitor ibrutinib and rituximab. Although his PNP lesions did not improve with ibrutinib monotherapy, the combination of ibrutinib and rituximab was effective against B-CLL/SLL-associated PNP. This case suggests that ibrutinib plus rituximab may be a potent therapeutic option for B-CLL/SLL-associated PNP that is hard to control with ibrutinib alone.

The authors report a man who developed oral dyskinesia at 46 years of age, followed by slowly progressive choreic movement and mild cognitive impairment over 20 years. He showed caudate atrophy and four types of intracranial calcification in the hippocampus (dot-like), cerebellar white matter (vague-mass), occipital cortices (laminar), and cerebral white matter (linear). Linear-calcification in the corona radiata seems to be deposition along small veins, which may be related to the white matter changes and to the decreased regional cerebral blood flow in the frontal and parietal lobes. The present case shows a slowly progressive disease with caudate atrophy and characteristic brain calcifications.

A 44-year-old woman with advanced metastatic colon cancer received chemotherapies comprising oxaliplatin and capecitabine (XELOX), irinotecan hydrochloride, leucovorin calcium and fluorouracil irinotecan (FOLFIRI)/panitumumab and mFOLFOX6/bevacizumab. Fifteen months later, she presented with the acute onset of a headache, drowsiness and seizure with a fever and hypertension. Brain magnetic resonance imaging (MRI) indicated bilateral regions of signal hyperintensity in the white matter with spasms of bilateral cerebral arteries apparent on magnetic resonance angiography. Posterior reversible encephalopathy syndrome (PRES) was diagnosed, and treatments resulted in improvement of the MRI findings, but the patient experienced cerebral infarction and ultimately died of deterioration of cancer on day 26 after the onset of PRES.

Lambert-Eaton myasthenic syndrome (LEMS) is most commonly associated with small cell lung carcinoma, while it is rarely associated with gynecological and breast carcinoma. We herein report a case of LEMS associated with synchronous double cancer, which was a combination of small cell carcinoma of the cervix and breast carcinoma. The early diagnosis and treatment of LEMS are important for achieving a good outcome. The possibility of accompanying paraneoplastic neurological syndrome must be sufficiently considered in gynecology and breast cancer patients. To our knowledge, this is the first report of LEMS associated with synchronous double cancer.

A 76-year-old man complicated with end-stage renal disease had latent tuberculosis infection (LTBI), and isoniazid (INH) 300 mg daily was started to prevent reactivation of LTBI before using biologic agents for rheumatoid arthritis. On the 8th day after administration of INH, he presented with a fever, petechiae, and myalgia. Serological studies revealed elevated myogenic enzymes and creatinine level. Based on the exclusion of other etiologies, rapid improvement with cessation of INH, and the recurrence of the fever and myalgia with re-administration of a reduced dose of INH, we diagnosed him with INH-induced rhabdomyolysis. Physicians should be aware of rhabdomyolysis induced by INH at a therapeutic dose as an infrequent but potentially fatal adverse drug reaction.

We describe a rare case of Propionibacterium acnes native-valve endocarditis that silently progressed in a 67-year-old man with hybrid dialysis. The patient was scheduled for kidney transplantation, and pre-operative investigation incidentally detected a vegetative structure at his native mitral valve that had increased in size. He underwent cardiac surgery and P. acnes was detected in cultures of a resected cardiac valve specimen and blood. This case highlights that P. acnes can silently cause infective endocarditis in a native-valve, and that physicians should consider the possibility of infection when P. acnes is isolated in blood cultures.

A 53-year-old woman was hospitalized due to septic shock after developing pneumococcal pneumonia after undergoing esophageal cancer surgery. Her transverse colon became perforated after receiving antimicrobial chemotherapy; therefore, emergency subtotal colectomy was performed. Fungi detected in both her colon tissue and a drainage sample indicated intestinal mucormycosis. Early intensive treatment with high-dose liposomal amphotericin B was successful, and she was subsequently discharged from the hospital. The fungal isolates were identified to be Lichtheimia ramosa and Aspergillus calidoustus via gene sequencing using panfungal primers as well as species-specific primers against elongation factor 1 and beta-tubulin for detecting Lichtheimia and Aspergillus, respectively.

Familial Mediterranean fever (FMF) is the most common genetic autoinflammatory disease, but it has been considered a rare disease in Japan. We herein describe five patients with FMF who were diagnosed both clinically and genetically at a single Japanese institute. A genetic investigation of Mediterranean fever (MEFV) detected heterozygosity for the compound mutations L110P/E148Q (n=2) and L110P/148Q/P369S/R406Q (n=1), and heterozygosity for M694I (n=1) and S503C (n=1). Colchicine prevented febrile attacks and accompanying symptoms in four patients. One patient with an S503C mutation showed resistance. Physicians should be aware of the characteristic symptoms, as well as the more unusual symptoms such as headache, when diagnosing FMF.

Solitary fibrous tumor (SFT) is a rare subtype of soft tissue sarcoma (STS). We herein describe a case of late onset of non-islet cell tumor hypoglycemia (NICTH) that was managed via multidisciplinary treatment in a patient with SFT. A 67-year-old man previously diagnosed with SFT 4 years prior to this presentation and treated with several rounds of surgery, presented with massive tumors. Eighteen months following his prescribed chemotherapy, the patient developed hypoglycemia. He was diagnosed with NICTH, after confirming the presence of high molecular weight insulin-like growth factor-2. This case suggests that paraneoplastic syndrome can occur even in cases of rare cancers, such as STS.