Objective Balloon-assisted endoscopy enables access to and treatment of strictures in the small intestine using endoscopic balloon dilation (EBD); however, the long-term outcomes of EBD have not been sufficiently evaluated. This study evaluated the long-term outcomes of EBD in Crohn's disease to identify the risk factors associated with the need for subsequent surgical intervention.

Methods We retrospectively analyzed patients with Crohn's disease who had undergone EBD with double-balloon endoscopy (DBE) for small intestinal strictures at a single center between 2006 and 2015. The long-term outcomes were assessed based on the cumulative surgery-free rate following initial EBD.

Results Seventy-two EBD with DBE sessions and 112 procedures were performed for 37 patients during this period. Eighteen patients (48.6%) required surgery during follow-up. Significant factors associated with the need for surgery in a multivariate analysis were multiple strictures (adjusted hazard ratio, 14.94; 95% confidence interval, 1.91-117.12; p=0.010). One patient (6.7%) required surgery among 15 who had single strictures compared to 17 (77.3%) among 22 patients with multiple strictures.

Conclusion In a multivariate analysis, the presence of multiple strictures was a significant risk factor associated with the need for surgery; therefore, a single stricture might be a good indication for EBD using DBE for small intestinal strictures in Crohn's disease patients.

Objective In Japan, metabolic syndrome (MetS) and preliminary metabolic syndrome (preMetS) are more prevalent in men; however, it remains unclear whether the relationship between these metabolic disorders and lifestyle factors is similar between genders.

Methods We examined waist circumference, blood pressure, fasting blood, and various lifestyle factors in 3,166 individuals aged from 30-79 years of age from the Japanese general population. MetS was diagnosed on the basis of central obesity - assessed by waist circumference - plus two or more of the following cardio-metabolic risks according to Japanese criteria: high blood pressure, hyperglycemia, and lipid abnormality. Central obesity plus one of the risks was defined as preMetS.

Results Men had a significantly higher prevalence of MetS (23.3% vs. 8.7%, p<0.001) and preMetS (21.2% vs. 10.2%, p<0.001) than women. An age-adjusted logistic regression analysis revealed that heavy drinkers were associated with an increased probability of MetS (odds ratio, 1.91: 95% confidence interval, 1.29-2.83) and preMetS (1.69: 1.11-2.58); fast eaters were also related to preMetS (1.83: 1.33-2.55) and MetS (1.55: 1.12-2.15) in men. Lacking regular exercise was significantly associated with preMetS (1.38: 1.03-1.85), but not MetS. In women, preMetS was significantly associated with fast eaters and lacking regular exercise (1.44: 1.01-2.07 and 1.41: 1.02-1.96, respectively); a stepwise increase in each odds ratio (2.02: 1.40-2.91 and 1.47: 1.03-2.09, respectively) was also observed for MetS.

Conclusion The relationships between lifestyle factors and MetS or preMetS differed between men and women, which suggests the need for gender-specific lifestyle modification to effectively prevent MetS.

Objective To analyze the clinical and endocrine characteristics of patients with primary adrenal lymphoma.

Patients We retrospectively reviewed the cases of five patients with primary adrenal lymphoma who were treated in our hospital between April 2004 and March 2015. We investigated the characteristics of the clinical and pathological findings, treatment, prognosis and complications of adrenal insufficiency.

Results Adrenal insufficiency, which was confirmed by the laboratory data at the initial presentation, was observed in two cases. One case was complicated by relative adrenal insufficiency during a course of chemotherapy. The plasma adrenaline and urinary adrenaline levels were decreased in four cases and three cases, respectively. Diffusion MRI was radiologically diagnostic. In all of the cases, the patients were pathologically diagnosed with diffuse large-B cell lymphoma and were treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like chemotherapy. Two patients received central nervous system prophylaxis with high-dose methotrexate. Four of the patients survived and one patient died during the follow-up period.

Conclusion The early detection of adrenal insufficiency and the administration of an appropriate dose of hydrocortisone are necessary during the course of chemotherapy as well as at the initial manifestation. The exclusion of adrenal dysfunction prior to invasive diagnostic procedures, such as CT-guided needle biopsy, is also critical.

Objectives We aimed to identify the factors that predict the likelihood of remission based on a health assessment questionnaire (HAQ) in rheumatoid arthritis (RA) patients who received non-tumor necrosis factor (TNF) biologics for six months before they commenced definitive treatment.

Methods The subjects consisted of 97 RA patients treated with tocilizumab or abatacept for 6 months. The following characteristics were investigated: age, gender, body mass index, steroid and methotrexate dosage, serum matrix metalloproteinase-3 levels, simplified disease activity index (SDAI) score, HAQ score (for assessing the activities of daily living [ADL]) and the short form (SF)-36 score (for assessing the quality of life [QOL]). Remission based on the HAQ score is defined as HAQ ≤0.5 after 6 months of treatment. The subjects were divided into two groups: patients with HAQ score ≤0.5 and HAQ score >0.5, and a retrospective study was conducted.

Results The group of RA patients who entered remission based on the HAQ (53 patients) had a lower SDAI than the patients who did not enter remission (44 patients), and the RA patients had a lower tender joint count (TJC) and HAQ scores and a lower physician's global assessment (PGA) than those who did not enter remission. The physical component summary score (PCS) and role/social component summary score (RCS) of the SF-36 summary score were higher in the remission patients than in those without. Before the start of the treatment, the HAQ score, patients' global assessment (PtGA) and PCS and mental component summary score (MCS) of the SF-36 were determined based on a logistic regression analysis.

Conclusion Our findings suggest that RA patients with lower HAQ scores and PtGA and higher PCS and MCS of the SF-36 at baseline are more likely to achieve HAQ remission with non-TNF biologic treatment than others.

A 62-year-old woman was admitted to our hospital with septic shock due to left submandibular osteomyelitis and cellulitis. Her condition improved following tooth extraction, drainage, and the administration of antibiotics. However, on the 4th day of hospitalization, she went into hemorrhagic shock after defecating a massive tarry stool. Emergency esophagogastroduodenoscopy (EGD) was performed. We found a giant ulcer at the antral greater curvature of the stomach. Computed tomography (CT) revealed that the gastric ulcer had penetrated the pancreas. She had no signs of peritonitis and had a bad general condition. She was therefore managed solely by conservative therapy. She recovered within days.

We herein report a rare case of a 79-year-old man who presented with the simultaneous occurrence of pancreatic neuroendocrine tumors (PNET) and renal cell carcinomas (RCC), without any other Von Hippel-Lindau (VHL)-associated lesions or any pertinent family history. Computed tomography showed vascular-rich solid lesions in the left kidney and the pancreatic tail, measuring 72 mm and 15 mm in size, respectively. Preoperatively, RCC with pancreatic metastasis was suspected and laparotomy was performed. However, the resected specimens revealed a different tumor histology, namely renal clear cell carcinoma (G2, pT3) and PNET (G1, pT3). The patient and his family refused genetic testing, however, so far, the patient has not developed any VHL-associated lesions for more than four years.

We describe the case of a 37-year-old woman who presented with complete right bundle branch block and right axis deviation. She was admitted to our hospital due to severe heart failure and was dependent on inotropic agents. Cardiac resynchronization therapy was initiated but did not improve her condition. After the optimization of the pacing timing, we performed earlier right ventricular pacing, which led to an improvement of her heart failure. Earlier right ventricular pacing should be considered in patients with complete right bundle branch block and right axis deviation when cardiac resynchronization therapy is not effective.

A 49-year-old Japanese man with worsening dyspnea was admitted with the diagnosis of new-onset heart failure (HF). His HF symptoms improved with standard treatment, but his left ventricular ejection fraction (LVEF) 21% remained unchanged. After he was discharged, he was diagnosed with severe sleep-disordered breathing (SDB). Continuous positive airway pressure (CPAP) therapy was introduced. Seven months later, his cardiac function had greatly improved (LVEF 50%). We report this case of a HF patient with SDB whose cardiac function greatly improved by CPAP therapy, and we discuss the pathophysiologic mechanisms of successful cardiac "reverse remodeling" in this case.

A 75-year-old woman who had previously been diagnosed with Bland-White-Garland syndrome was admitted to our hospital for acute decompensated heart failure (ADHF). Following her recovery from ADHF, pharmacologic stress myocardial scintigraphy revealed myocardial ischemia in the basal anterior area of the left ventricle. Moreover, myocardial scintigraphy showed the improvement of the myocardial ischemia after 6 months of nicorandil administration.

We herein report an 87-year-old woman who was taking clonazepam at 1.5 mg/day. She was hospitalized with an old cerebral infarction complicated with symptomatic epilepsy, dementia, dyslipidemia, and chronic cholecystitis. Electrocardiogram revealed severe bradycardia at 31 beats/min. The bradycardia disappeared on day 3 after clonazepam withdrawal, although the serum clonazepam level had been within normal limits. She was diagnosed with clonazepam-associated bradycardia, which was likely related to the potential calcium channel-blocking properties of clonazepam. Because of age-related pharmacokinetic and pharmacodynamic changes, the adverse effects of clonazepam should be considered, especially in disabled elderly individuals with multiple comorbidities.

A 39-year-old man with nephrotic syndrome was admitted due to right dorsal pain. Contrast-enhanced CT led to a diagnosis of renal vein thrombosis and segmental pulmonary thromboembolism. Treatment with heparin and warfarin was started. After 1 month, pulmonary thromboembolism recurred. Warfarin was switched to edoxaban, and steroid therapy was initiated, which led to the remission of nephrotic syndrome and the disappearance of renal vein thrombosis. The efficacy of edoxaban was demonstrated; however, this drug has not been routinely selected for patients with renal disease. Our results suggest that edoxaban is also effective for treating venous thrombosis patients with nephrotic syndrome.

Although nivolumab is known to cause immune-related interstitial lung diseases (ILD), the detailed characteristics of ILD are still not fully understood. A 68-year-old man was treated with nivolumab because of unresectable sinonasal melanoma, he achieved a complete response soon after the initiation of the therapy and a complete response was thereafter maintained for 30 weeks until the patient experienced dyspnea of subacute onset. CT images revealed patchy infiltrates and ground-glass opacifications. The bronchoalveolar lavage fluid (BALF) contained elevated percentages of lymphocytes (53%) and neutrophils (30%). A transbronchial lung biopsy revealed intraalveolar fibrin balls without hyaline membranes, which was considered to be consistent with the pattern of acute fibrinous and organizing pneumonia (AFOP). This is the first report of AFOP induced by nivolumab.

Choroidal metastasis is rare in cancer patients and it may cause visual disturbances that reduce their quality of life. In non-small cell lung cancer (NSCLC), targeted therapy against actionable driver mutations has gradually replaced radiotherapy as the treatment of choice for choroidal metastasis. Recently, there have been several case reports of choroidal metastasis in patients with anaplastic lymphoma kinase (ALK)-rearranged NSCLC. We herein report the case of a 40-year-old Japanese woman diagnosed with choroidal metastasis of an ALK-rearranged NSCLC who received alectinib as the first-line chemotherapy. Alectinib may be the best treatment for choroidal metastasis in patients harboring an ALK translocation because of its favorable side effect profile involving visual disturbances.

Crizotinib, which is effective in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer, is sometimes associated with the generation of complex renal cysts. A 56-year-old man with ALK positive adenocarcinoma received crizotinib. Ten months after the introduction of crizotinib, a cystic lesion developed from his right kidney to the iliopsoas muscle, accompanied by fever, anemia, and hypoproteinemia. After 17 months of treatment, crizotinib was switched to alectinib, followed by the recovery of hypoproteinemia and systemic inflammation. Switching to alectinib may be beneficial in patients demonstrating crizotinib-associated complex renal cysts with systemic inflammation and exhaustion.

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib.

Early-onset pulmonary emphysema is uncommon and its pathogenesis is poorly defined. A 30-year-old man was admitted to our intensive care unit with severe respiratory failure. Besides smoking heavily since the 14 years of age, he had habitually inhaled organic solvents, such as toluene, in his adolescence. High-resolution computed tomography showed evident pulmonary emphysema throughout the lung fields. Based on the findings of right heart catheterization, he was diagnosed with an acute exacerbation of chronic obstructive pulmonary disease complicated with pulmonary hypertension. Heavy smoking from a young age and exposure to toluene were the suspected causes of the patient's severe pulmonary emphysema.

The development of tumor lysis syndrome (TLS) in association with treatment for myeloproliferative neoplasms (MPNs) is relatively rare. We herein present the case of a post-polycythemia vera (PV) myelofibrosis patient with massive splenomegaly who developed laboratory TLS after treatment with ruxolitinib, a potent JAK1/JAK2 inhibitor. She also exhibited a rapid reduction of spleen volume. Our present case suggests the potential risk of TLS development after ruxolitinib treatment, particularly in patients with massive splenomegaly.

Antithrombin (AT) deficiency, a rare disorder of the coagulation system, is a serious risk factor for thromboembolism. Approximately 50-90% of patients with AT deficiency develop thromboembolism during their lifetime. In addition, surgery is a major risk factor for thromboembolism in these patients. We herein report the case of a 90-year-old woman with AT deficiency who was safely and successfully managed using rivaroxaban (a direct oral factor Xa inhibitor) during the perioperative period of surgery for right femur fracture. The present case illustrates the effectiveness of rivaroxaban in preventing thromboembolisms due to surgery, even in very elderly patients with antithrombin deficiency. Further investigations are needed to determine the optimal dosage of rivaroxaban.

The diagnosis of aortic dissection (AD) is sometimes difficult within the limited time window of recombinant tissue plasminogen activator (tPA) for ischemic stroke (IS). A 60-year-old man developed sudden left hemiparesis due to IS. During tPA infusion, his blood pressure dropped and consciousness declined. After transfer to our hospital, carotid duplex ultrasonography led to a diagnosis of AD. Emergency surgery was postponed because of the risk of hemorrhagic transformation. The patient successfully underwent aortic surgery on day 5 and was discharged with a remarkable improvement in his symptoms. Delayed surgery may avoid hemorrhagic transformation in patients with AD-induced IS who have received tPA.

A 41-year-old man presented with gradually progressing proximal-dominant lower limb atrophy and weakness. His brother, mother and maternal aunt had the same symptoms. A physical examination and muscle imaging (CT and ultrasound) showed selective muscle involvement of the bilateral paraspinal, gluteus and posterior groups of lower limb muscles. Based on the characteristic muscle involvement pattern, the clinical findings and the muscle biopsy results, we made a straightforward diagnosis of limb-girdle muscular dystrophy (LGMD) due to a DNAJB6 Phe93Leu mutation based on a targeted gene analysis. In the differential diagnosis of adult-onset LGMD syndromes, in addition to investigating the family history, it is important to perform an extensive physical examination to determine the pattern of muscle involvement, and to perform a muscle biopsy. Our case suggests that posterior-dominant lower limb muscle impairment with gluteus and truncal muscle involvement and the detection of rimmed vacuoles on a muscle biopsy could be clues for the diagnosis of LGMD due to DNAJB6 mutations.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder that generally occurs in children and predominantly affects the long bones with marginal sclerosis. We herein report two cases of adult-onset CRMO involving the tibial diaphysis bilaterally, accompanied by polyarthritis. Magnetic resonance imaging (MRI) showed both tibial osteomyelitis and high intensity of the extensive lower leg muscles. Anti-interleukin-6 therapy with tocilizumab (TCZ) effectively controlled symptoms and inflammatory markers in both patients. High intensity of the lower leg muscles detected by MRI also improved. These cases demonstrate that CRMO should be included in the differential diagnosis of adult patients with bone pain, inflammation, and high intensity of the muscles detected by MRI. TCZ may therefore be an effective therapy for muscle inflammation of CRMO.

We herein report the case of a 68-year-old woman with a skin and soft tissue infection at her extremities. The blood culture results were positive for Streptococcus pyogenes, and we started treatment using ampicillin and clindamycin, although subsequent auscultation revealed a new-onset heart murmur. We therefore suspected rheumatic heart disease and infective endocarditis. The case met both the Jones criteria and the modified Duke criteria. Transesophageal echocardiography revealed vegetation on the aortic valve, although the pathological findings were also compatible with both rheumatic heart disease and infective endocarditis. The present findings suggest that these two diseases can coexist in some cases.

Chemotherapy for multiple primary cancers is challenging. We describe a case of synchronous duodenal cancer with lung cancer harboring an epidermal growth factor receptor (EGFR) mutation treated with erlotinib and S-1, an oral fluoropyrimidine agent. A 78-year-old woman with advanced EGFR-mutated lung adenocarcinoma was simultaneously diagnosed with duodenal adenocarcinoma. After the treatment with erlotinib, the lung cancer responded well, but her duodenal cancer showed no response. S-1 was added to erlotinib, and the duodenal cancer demonstrated a good response with tolerable toxicities. The concurrent use of erlotinib and S-1 was safe and efficacious for synchronous lung cancer harboring an EGFR mutation and duodenal cancer.