Objective We have recently discovered new gastric lesions with black spots. There have been no reports about black spots and their clinicopathological features. We therefore report the clinicopathological features of black spots and assess their causes and mechanisms.

Methods Sixty-four patients with black spots among 26,620 Japanese patients that underwent endoscopy between May 2012 and October 2014 were enrolled. Endoscopic findings of black spots were defined as black pigmentations in the gastric mucosa by conventional endoscopy. We investigated the clinicopathological characteristics, including gender, age, underlying diseases and medications, endoscopic and pathologic findings of patients with black spots.

Results The prevalence of patients with black spots was 0.24%. Of sixty-four cases, 44 (68.8%) were taking proton pump inhibitors (PPIs). Eight (12.5%) were taking corticosteroids. There were 10 cases (15.6%) with decreased renal function. All black spots were identified only in the fundic gland region. Forty-one (64.1%) patients had multiple (more than ten) black spots. There were two different types: black spots on the flat mucosa and black spots on fundic gland polyps. Pathologically, parietal cell protrusions, fundic gland cysts and brownish pigmentation in fundic gland cysts were seen in 26 (76.5%), 23 (67.6%) and 6 (17.6%) patients, respectively.

Conclusion We herein describe gastric black spots as a new gastric mucosal finding that arises only in the fundic gland region. The black spots are pathologically brownish pigmentations in fundic gland cysts. Adverse events of PPIs and parietal cell protrusion caused by PPI use are strongly considered to be one of the etiologies of black spots.

Objective Metabolic syndrome (MetS) is associated with cardiovascular disease, which is the leading cause of mortality and morbidity. Hypernatremia and hypochloremia are also associated with an increased mortality. Thus, the aim of this study was to evaluate the association between the sodium-chloride difference (Na⁺-Cl^-) and MetS.

Methods In this cross-sectional and retrospective cohort study, we enrolled 3,875 subjects and evaluated the relationship between Na⁺-Cl^- and MetS using logistic regression analyses. MetS was diagnosed according to the joint interim statement when a subject had three or more of the following criteria: hypertension; hyperglycemia; hypertriglyceridemia; low high-density lipoprotein (HDL) cholesterol; and abdominal obesity.

Results There were 3,354 subjects without MetS and 521 subjects with MetS at baseline. The highest Na⁺-Cl^- quartile (≥43 mmol/L) was associated with an increased risk of the presence of MetS compared to the lowest Na⁺-Cl^- quartile (≤38 mmol/L) after adjusting for covariates, including age, sex, the body mass index, systolic blood pressure, fasting plasma glucose, triglycerides, HDL cholesterol, creatinine, uric acid and lifestyle factors [multivariate odds ratio (OR) 1.81, 95% confidence interval (CI) 1.17-2.84, p=0.0078]. After an 8-year follow-up, 658 out of 3,352 subjects were newly diagnosed with MetS. The highest Na⁺-Cl^- quartile (≥43 mmol/L) was associated with an increased risk of the development of MetS compared to the lowest Na⁺-Cl^- quartiles (≤38 mmol/L) after adjusting for covariates (multivariate OR 1.76, 95% CI 1.27-2.45, p=0.0007).

Conclusion The sodium and chloride difference is associated with MetS.

Objective Visceral fat obesity and metabolic syndrome correlate with atherosclerosis in part due to insulin resistance and various other factors. The aim of this study was to determine the relationship between vascular endothelial dysfunction and excess visceral adipose tissue (VAT) in Japanese patients with type 2 diabetes mellitus (T2DM).

Methods In 71 T2DM patients, the reactive hyperemia index (RHI) was measured using an Endo-PAT 2000, and VAT and subcutaneous adipose tissue (SAT) were measured via CT. We also measured various metabolic markers, including high-molecular-weight adiponectin (HMW-AN).

Results VAT correlated negatively with the natural logarithm of RHI (L_RHI), the primary endpoint (p=0.042, r=-0.242). L_RHI did not correlate with SAT, VAT/SAT, abdominal circumference, homeostasis model assessment for insulin resistance, urinary C-peptide reactivity, HMW-AN, or alanine amino transferase, the secondary endpoints. A linear multivariate analysis via the forced entry method using age, sex, VAT, and smoking history as independent variables and L_RHI as the dependent variable revealed a lack of any determinants of L_RHI.

Conclusion Excess VAT worsens the vascular endothelial function, represented by RHI which was analyzed using Endo-PAT, in Japanese patients with T2DM.

Objective The impact of dialysis initiation on survival is still somewhat controversial. Given that race or ethnicity has been observed to be a predictor of mortality and the rate of progression of chronic kidney disease, we conducted a meta-analysis to investigate the effect of early vs. late dialysis initiation on mortality in East Asian populations.

Methods All eligible cohort studies of target were selected from the MEDLINE (PubMed), EMBASE, The Cochrane Library and the Clinical Trials Registry databases from inception to October 2014. The data were extracted with all-cause mortality rates as the primary outcome, and pooled adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated.

Results Ten studies examined the association between early vs. late dialysis initiation and mortality. Compared to late dialysis initiation, patients who received early dialysis initiation had a higher overall mortality risk (adjusted HR, 1.36; 95% CI, 1.0-1.85; p<0.05) in East Asian populations. In a subgroup analysis, baseline characteristic differences (adjusted HR, 2.0; 95%CI, 1.56-2.57; p<0.001), initial dialysis modalities (adjusted HR, 2.12; 95% CI, 1.72-2.62; p<0.001) and follow up duration (adjusted HR, 1.59; 95% CI, 1.19-2.12; p=0.002), demonstrated that the association between early dialysis initiation and mortality were significant.

Conclusion A higher glomerular filtration rate (early) at the initiation of dialysis is associated with a higher all-cause mortality risk in East Asian populations.

Objective A mutational analysis of tumor tissue samples is an important part of advanced lung cancer treatment strategies. This study evaluated the efficacy of a triple gene analysis using samples obtained via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).

Methods Either metastatic lymph nodes or primary lung mass samples obtained by EBUS-TBNA were collected between May 2011 and May 2013. We consecutively analyzed epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), and anaplastic lymphoma kinase (ALK) fusion genes using remnant tissue samples.

Results A total of 109 patients were diagnosed with non-small cell lung cancer (NSCLC). Of these, 70% were adenocarcinoma, 27% squamous cell carcinoma with NSCLC, and 3% were related to other types of lung cancer. EGFR mutations were detected in 23 cases (21.1%), KRAS mutations in 13 cases (11.9%), and ALK fusion genes in 5 cases (4.9%). The ALK fusion genes could not be analyzed in four cases because of insufficient tissue samples remaining after routine histochemistry and an EGFR/KRAS mutation analysis. We found that small biopsy samples from EBUS-TBNA were adequate for performing a triple gene analysis in 97 patients (96%). ALK fusion protein immunohistochemistry (IHC) was 100% consistent with fluorescence in situ hybridization (FISH).

Conclusion Small samples obtained by EBUS-TBNA were found to be sufficient for performing a triple gene analysis following routine histology and IHC. ALK IHC showed a very good concordance with FISH for detecting ALK fusion genes.

Objective Pain and cognitive impairment are important clinical features in patients with Parkinson's disease (PD). Although pain processing is associated with the limbic system, which is also closely linked to the cognitive function, the association between pain and cognitive impairment in PD is still not well understood. The aim of the study was to investigate the association between pain processing and cognitive impairment in patients with PD.

Methods Forty-three patients with PD and 22 healthy subjects were studied. Pain-related somatosensory evoked potentials (SEPs) were generated using a thin needle electrode to stimulate epidermal Aδ fibers. Cognitive impairment was evaluated using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery, and Japanese version of the Montreal Cognitive Assessment (MoCA-J), and their correlation with pain-related SEPs was investigated.

Results The N1/P1 amplitude was significantly lower in PD patients than the controls. N1/P1 peak-to-peak amplitudes correlated with the MMSE (r=0.66, p<0.001) and MoCA-J scores (r=0.38, p<0.01) in patients with PD. These amplitudes also strongly correlated with the domains of attention and memory in the MMSE (attention, r=0.52, p<0.001; memory, r=0.40, p<0.01) and MoCA-J (attention, r=0.45, p<0.005; memory, r=0.48, p<0.001), but not in control subjects.

Conclusion A good correlation was observed between the decreased amplitudes of pain-related SEPs and an impairment of attention and memory in patients with PD. Our results suggest that pathological abnormalities of the pain pathway are significantly linked to cognitive impairment in PD.

Objective The influence of cancer boards with respect to the treatment decisions regarding chemotherapy remains to be elucidated. In the present study, we investigated the cases that presented at our institutional cancer boards, to assess the effect of cancer boards on the treatment decisions regarding chemotherapy.

Methods Data from the cancer boards at Yamagata University Hospital, Yamagata, Japan, were collected. Along with data from the clinical records, the details of the discussions and the chosen plan of treatment of the cancer boards were analyzed.

Results From February 2010 to February 2014, 1,541 cases were discussed at our cancer boards. Of these, 811 cases (52.6%) involved discussions about chemotherapy. Of those 811 cases, recommendations were made to alter the treatment plans for 189 cases (23.3%). The reasons for discouraging chemotherapy varied; however, 29/45 (64.4%) cases involved discouragement for the following reasons: old age, a comorbid condition, the physical (performance) status, or insufficient evidence to administer chemotherapy. Eighty-six patients were referred to the medical oncology department through the cancer boards.

Conclusion Our results showed that cancer boards have a great influence on the treatment decisions regarding chemotherapy and the prompt referral of cases to medical oncologists as necessary. In terms of future research, we will evaluate the effect of cancer boards on the prognosis and outcomes of cases using the institutional cancer registry.

The patient was a 57-year-old man who was diagnosed with multiple lung metastases of sigmoid colon cancer. The patient developed progressive disease after 8 courses of bevacizumab + capecitabine and oxaliplatin therapy, therefore, bevacizumab + irinotecan, leucovorin, and 5-fluorouracil therapy was started. During the fifth course, he experienced pain on the left side of his chest. On computed tomography, bleeding from the pulmonary metastatic lesions was suspected. Two days later, a pneumothorax was detected. Although several cases of pneumothorax induced by bevacizumab have been reported, this case is the first documentation that bevacizumab caused a rupture of the lung metastatic lesion, leading to a pneumothorax.

Endoscopic treatment for superficial non-ampullary duodenal tumors is technically difficult and challenging due to the anatomical characteristics of the duodenum. It is frequently complicated by procedural accidents, such as perforation. Surgical repair has long been the standard treatment for acute iatrogenic gastrointestinal perforation. However, endoscopic closure has recently emerged as an attractive alternative. In the patient presented herein, the over-the-scope-clipping system (OTSC system) was found to be useful for closing a duodenal perforation that had occurred during endoscopic submucosal dissection. For endoscopists who perform endoscopic treatment of the duodenum, endoscopic closure with the OTSC system is considered to be a technique that is necessary to master.

Epidermoid cysts presenting within an intrapancreatic accessory spleen are rare non-neoplastic cysts typically occurring in the pancreatic tail. This entity is difficult to diagnose given there are many types of pancreatic neoplastic cysts. We herein describe two cases of an epidermoid cyst within an intrapancreatic accessory spleen for which we performed a resection by laparoscopic distal pancreatectomy. Epidermoid cysts in an intrapancreatic accessory spleen should therefore be considered in the differential diagnosis of pancreatic tail cystic lesions. Laparoscopic distal pancreatectomy can be a useful, minimally invasive surgical approach for treating these cysts as well as for the treatment of benign or low-grade malignant tumors located in the pancreatic body or tail.

Varicella zoster virus (VZV) infection does not always provide lifelong immunity. A reinfection with VZV occurs more commonly than previously thought. Varicella infection spreads through the blood-stream, causing pneumonia. Varicella pneumonia results in bilateral pulmonary nodular infiltrations. We herein report a case of varicella reinfection with unilateral varicella pneumonia in which a reduced pulmonary blood flow due to radiation damage was considered to be the cause of unilateral pneumonia. In patients with an asymmetric pulmonary blood flow, careful interpretation of unilateral infiltration is therefore considered to be important with making a differential diagnosis.

Primary mediastinal large B-cell lymphoma (PMLBCL) is one of the subtypes of diffuse large B-cell lymphoma. We experienced a rare case of PMLBCL that exhibited endobronchial involvement. A 33-year-old Japanese female with the chief complaints of epigastralgia, back pain, and nausea visited a primary care hospital. Computed tomography of the chest and abdomen demonstrated a bulky mass in the left anterior mediastinum, multiple pulmonary nodules, axillary lymph node swelling, and a pancreatic tumor. Fiberoptic bronchoscopy showed a white-tinged irregularly shaped endobronchial tumor accompanied by capillary vessel dilation in the left upper lobar bronchus. Taken together, these findings resulted in a diagnosis of PMLBCL.

This is the first report in which crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, reduced an atypical carcinoid tumor with ALK rearrangement. A 70-year-old man developed a tumor in the left lung and multiple metastases to the lung and brain. The pathology of transbronchial biopsied specimens demonstrated an atypical carcinoid pattern. Combined with immunohistochemical findings, we diagnosed the tumor as atypical carcinoid. ALK gene rearrangement was observed by both immunohistochemical (IHC) and fluorescence in situ hybridization. He was treated with chemotherapy as first-line therapy, however, the tumor did not respond to chemotherapy. Thereafter, he was treated with crizotinib, which successfully reduced the tumors.

A 62-year-old man with myelodysplastic syndrome (MDS) presented to our hospital with a high fever. Although treatment with broad-spectrum antibiotics was initiated, his respiratory status worsened to the point that he required mechanical ventilation. However, he was successfully treated with a corticosteroid without immunosuppression. Sequential transbronchial lung biopsies revealed abundant fibrin exudate in the alveolar spaces, which was subsequently replaced by fibroblasts, showing that acute fibrinous and organizing pneumonia (AFOP) gradually changes into organizing pneumonia. Our case demonstrated both the efficacy of corticosteroid-monotherapy and the histological course of AFOP.

Primary pericardial malignant mesothelioma is a very rare clinical entity and its prognosis is very poor. We herein report a 67-year-old man who presented with pericardial mesothelioma that was diagnosed 21 months after the onset of cardiac tamponade as the initial manifestation. Despite undergoing pericardiocentesis and surgical pericardial fenestration at the onset of cardiac tamponade, we were unable to make a conclusive diagnosis of mesothelioma based on the cytological and histological findings. This unusual case had a relatively long progression-free period without treatment before the appearance of pleural tumors that showed the histological features of malignant sarcomatoid mesothelioma.

Tracheobronchopathia osteochondroplastica (TO) is a rare benign airway disease that is characterized by the presence of multiple rock-garden-like nodules on bronchoscopy. TO is a slowly progressive disease of the trachea and major bronchi, which is typically characterized by such symptoms as a persistent nonproductive cough, dyspnea and wheezing. The clinical features of TO are variable, and asymptomatic patients may incidentally be diagnosed during the work-up for other diseases. We herein report a rare case of TO accompanying multiple tracheobronchial polyposis in which bronchoscopic resection of the airway polyp using a high-frequency snare was successfully performed.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal diffuse large B-cell lymphoma, which is characterized by the intravascular growth of lymphoma cells, aggressive behavior, and an often fatal course. Patients with IVLBCL are usually symptomatic. Although any organ may be involved, localized lesions in the bilateral ovaries and uterus are extremely rare. We experienced a rare case of IVLBCL involving the bilateral ovaries and uterus in an asymptomatic patient with a t(11;22)(q23;q11) constitutional balanced translocation. Its association with the disease remains unknown. Even in asymptomatic situations, IVLBCL is possible, and the uterus and ovaries can be involved.

Toxoplasmic encephalitis is a rare infectious complication in patients with hematological malignancy except for allogeneic hematopoietic stem cell transplantation (HSCT). We herein report a case of possible toxoplasmic encephalitis with untreated hairy cell leukemia variant. Magnetic resonance imaging showed multiple nodules with surrounding edema in the entire cerebrum. A polymerase chain reaction analysis for Toxoplasma gondii was negative. Her signs and symptoms fully recovered by empirical therapy with sulfadiazine and pyrimethamine. Toxoplasmic encephalitis may occur in patients who undergo non-allogeneic HSCT for hematological malignancies, even in those who have not been treated.

We herein present two cases of acute disseminated encephalomyelitis (ADEM) following vaccination against human papilloma virus (HPV). Case 1 experienced diplopia and developed an unstable gait 14 days after a second vaccination of Cervarix. Brain magnetic resonance imaging (MRI) showed an isolated small, demyelinating lesion in the pontine tegmentum. Case 2 experienced a fever and limb dysesthesia 16 days after a second vaccination of Gardasil. Brain MRI revealed hyperintense lesion in the pons with slight edema on a T2-weighted image. Both cases resolved completely. It is important to accumulate further data on confirmed cases of ADEM temporally associated with HPV vaccination.

A 39-year-old woman with a 3-year history of a rounded face developed widespread myalgia. Detailed examinations revealed no disorders that could explain the pain other than concomitant Cushing's disease and central hypothyroidism. Both the hypercortisolemia and hypothyroidism completely resolved after the patient underwent surgery to treat Cushing's disease, but she continued to experience unresolved myalgia and met the diagnostic criteria for fibromyalgia. Few studies have so far investigated patients with fibromyalgia associated with Cushing's syndrome. In our case, the hypothyroidism caused by Cushing's disease probably played an important role in triggering and exacerbating fibromyalgia. This highlights the need to examine the endocrine function in patients with muscle pain.

A 61-year-old man had hypertension with stenosis in the left renal artery. When his fever, abdominal pain, and renal dysfunction progressed, he was admitted to our hospital. He was diagnosed with polyarthritis nodosa. His renal function rapidly deteriorated despite immunosuppressive therapy. His digestive tract perforated twice, and he subsequently died. An autopsy revealed that aortic intimal sarcoma caused stenosis in multiple arteries. Both polyarteritis nodosa and aortic intimal sarcoma are very rare diseases and the diagnoses are very difficult. It is very important to consider these entities when making a differential diagnosis of vasculitis.

Polyarteritis nodosa (PAN) confined to the muscle is rare and hard to diagnose. Recently, the utility of magnetic resonance imaging (MRI) for detecting muscle involvement of PAN has been introduced. We herein report the case of biopsy-proven, refractory PAN confined to the lower limb muscles with enhanced MRI demonstrating discretely granular hyperintensities, which was contrary to previous reports. Our results, with those of previous reports, suggest that the MRI findings of muscles in PAN reflect the vessel size involved and disease severity.

A 36-year-old woman developed hypokalemic metabolic alkalosis after anti SS-A antibody was found to be positive. Diuretic loading test results were compatible with Gitelman syndrome (GS). The patient had a heterozygous mutation in SLC12A3, which encodes for thiazide-sensitive NaCl cotransporter (NCCT). While the mutation may be responsible for a latent hypofunction of NCCTs, the underlying anti-SSA antibody-associated autoimmunity induced the manifestation of its hypofunction. To the best of our knowledge, this is the first report to demonstrate that anti SS-A antibody-associated autoimmunity may induce GS in a patient with a SLC12A3 heterozygous mutation.

A 71-year-old woman with polymyositis presenting with left thigh pain and an intermittent fever was admitted to Osaka Rosai Hospital. We initially diagnosed that her pain and fever were caused by a soft tissue infection because her polymyositis was controlled. She did not respond to various antibiotic therapies. Chest computed tomography demonstrated miliary tuberculosis (TB). Ziehl-Neelsen staining of liver biopsy specimens revealed epithelioid cell granuloma and acid-fast bacilli. Therefore, we finally diagnosed the lesion as TB fasciitis that improved with anti-TB drug therapy. The atypical presentation of TB fasciitis demonstrates the clinical importance of eliminating TB infections in immunocompromised hosts.

Streptococcal toxic shock syndrome caused by group B streptococcus (GBS) is a rare, but lethal disease. We experienced a 45-year-old woman with pustular psoriasis who developed toxic shock-like syndrome during infliximab treatment. Surprisingly, similar episodes recurred three times in one year with restarting of infliximab treatments. In the third episode, GBS were detected in blood, urine, and vaginal secretion cultures. These episodes of shock syndrome were possibly due to GBS. To the best of our knowledge, this is the first case report of recurrent streptococcal toxic shock syndrome possibly caused by GBS which was induced by anti-TNF-α inhibitor therapy. The restarting of biological agents in patients with a history of toxic shock syndrome should therefore be avoided as much as possible.

A 49-year-old female was referred to our hospital due to high serum creatine kinase (CK) (2,605 IU/L) and serum cardiac troponin T (cTnT) (0.342 ng/mL) levels. She had no other complaints and further examinations suggested no signs of cardiac disease. Additionally, the serum cardiac troponin I (cTnI) levels were normal. She reported having gradually felt difficulty in walking upstairs. A biopsy indicated skeletal muscle sarcoidosis with positive staining for cTnT. Steroid therapy immediately resolved her muscular symptoms with a normalization of the serum CK levels. Since the serum levels of cTnI were normal, the concomitant measurement of cTnT/cTnI might be useful to diagnose skeletal muscular disease biochemically in such cases.