Objective Differentiated gastric cancer generally develops in the atrophic gastric mucosa, although undifferentiated cancer is sometimes encountered in patients with severe atrophic gastritis. We characterized the endoscopic features of undifferentiated gastric cancer in patients with severe atrophic gastritis.
Methods Stage IA early gastric cancer was diagnosed in 501 patients who were admitted to our hospital between April 2003 and March 2012. The endoscopic and pathological findings were compared among 29 patients with undifferentiated cancer and severe atrophic gastritis, 104 patients with undifferentiated cancer and mild/moderate atrophic gastritis and 223 patients with well-differentiated cancer and severe atrophic gastritis. Endoscopic atrophic gastritis was classified according to the Kimura-Takemoto classification as no gastritis, C-1 and C-2 (mild), C-3 and O-1 (moderate) or O-2 and O-3 (severe).
Results The tumors were larger and showed deeper mural invasion in the patients with undifferentiated cancer and severe atrophic gastritis than in those with well-differentiated cancer and severe gastritis or undifferentiated cancer and mild/moderate gastritis. On endoscopy, undifferentiated cancer associated with severe gastritis was often red in color.
Conclusion It is often difficult to diagnose early undifferentiated gastric cancer, especially in patients with severe atrophic gastritis. The present study characterized the important endoscopic features of such tumors.

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Objective Although the prognosis is known to be poor in cirrhosis patients associated with sarcopenia, the relationships among skeletal muscle, visceral fat, and the liver have not yet been thoroughly investigated. Therefore, the prognosis and its associations with body composition and the severity of liver disease were examined in patients with cirrhosis.
Methods The skeletal muscle mass and visceral fat area were measured in 161 patients with cirrhosis, the effects of body composition on the prognosis were analyzed, and any factors that contribute to changes in body composition were assessed.
Results During the mean observation period of 1,005 days, 73 patients died. Patients with sarcopenia or sarcopenic obesity had a poor prognosis, and this difference was pronounced in the subset of patients classified as Child-Pugh class A. A decreased skeletal muscle mass was strongly correlated with decreased serum albumin levels. Sarcopenia is a common feature of advanced cirrhosis, and transitions were observed from normal body composition to sarcopenia and from obese to sarcopenic obesity.
Conclusion The body composition is a prognostic factor for cirrhosis, and a better body composition may be advantageous for obtaining a long-term survival in patients with cirrhosis.

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Objective Chronic kidney disease is a risk factor of coronary events, however, its impact on coronary artery stenosis has not yet been clarified with the use of a large database. We examined the association between a reduced glomerular filtration rate (GFR) and the overall severity of coronary stenosis.
Methods We enrolled 1,150 patients [mean age, 68±12 (SD) years; 66.6% men] who consecutively underwent coronary angiography for suspected stable angina pectoris. The overall severity of stenosis in the coronary arteries was assessed by the Gensini score (GS), and its logarithmic values (log-GS) were used for statistical analyses since the GS does not follow a normal distribution.
Results The log-GS was significantly larger in men than in women (2.5±1.5 vs. 1.9±1.7), while the estimated GFR (eGFR) and comorbidities were comparable between both sexes. A multivariate regression analysis indicated that age, smoking, eGFR, HDL-cholesterol and HbA1c were independent explanatory variables of the log-GS in men, although the eGFR explained only 1.2% of the log-GS variation. In women, the eGFR was not included in the significant explanatory variables shown by the multivariate analysis. However, the sex difference in the regression for the eGFR-log-GS relationship was not statistically significant.
Conclusion A reduced eGFR is a significant, but minor, determinant of the overall severity of coronary artery stenosis in men and potentially women.

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Objective The administration of corticosteroids is a standard treatment for autoimmune hepatitis (AIH), but it can occasionally induce various adverse effects. Diabetes mellitus (DM) is a major complication of chronic liver diseases. We investigated the prevalence and risk factors of DM in patients with AIH.
Methods We retrospectively analyzed 118 Japanese patients diagnosed with AIH from 1990 to 2014 at our institution. The prognosis of patients with and without DM was also compared.
Results Twenty-nine (24.5%) patients had DM and 21 (72.4%) received corticosteroids. The annual cumulative incidence rate of newly diagnosed DM was 1.2%. Multivariate analysis showed that DM occurred in older patients [OR=6.290; 95% confidence interval (CI)=1.230-32.100; p=0.018] with higher serum immunoglobulin G levels (OR=12.400; 95% CI=2.560-60.400; p=0.002). A Cox hazard regression analysis revealed that predictive factors for DM were absence of other autoimmune diseases (OR=0.171; 95% CI=0.036-0.805; p=0.025), use of corticosteroids (OR=6.693; 95% CI=1.391-32.210; p=0.049) and lower platelet counts (OR=3.873; 95% CI=1.021-14.690; p=0.046). The 10 year survival rates of the DM and non-DM groups were 94.1% and 94.6%, respectively. There was no significant difference between these groups (p=0.293).
Conclusion DM occurred in 24.5% of patients with AIH; older age, absence of other autoimmune diseases and higher serum immunoglobulin G levels are risk factors. Taking corticosteroids and a lower platelet count are risk factors for a new onset of DM. DM did not influence the prognosis of AIH patients.

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Objective The optimal prognostic model for community-acquired pneumonia (CAP) remains unclear. In this study, we sought to identify independent predictors of 30-day mortality in patients with CAP and to determine whether adding specific prognostic factors to each of the two clinical prediction scores could improve the prognostic yield.
Methods This retrospective study involved 797 CAP patients who had been hospitalized at a tertiary referral center. The patients were categorized into two groups: those who survived and those who had died on or before 30 days after admission. Select clinical parameters were then compared between the two groups.
Results During the 30-day period, there were 72 deaths (9%). We constructed two models for a multivariate analysis: one was based on a high CURB-65 score (3-5) and the other on a high pneumonia severity index (PSI) class (V). In both models, a high CURB-65 score or a high PSI class, along with the presence of dyspnea, high Eastern Cooperative Oncology Group (ECOG) performance status (3-4), and a low serum albumin level, were independent predictors of 30-day mortality. In both the CURB-65-based and PSI-based models, the addition of dyspnea, high ECOG performance status, and hypoalbuminemia (<3 g/dL) enhanced the prognostic assessment, and subsequently, the c-statistics calculated with the use of three- or four- predictor combinations exceeded 0.8.
Conclusion In addition to the CURB-65 or PSI, the clinical factors of dyspnea, the ECOG performance status, and serum albumin level may be independent predictors of 30-day mortality in CAP patients. When combined with the CURB-65 or PSI, these parameters provide additional evidence for predicting poor prognoses.

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Objective Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus. Recent data suggest that the physiological balance of multiple proinflammatory cytokines is substantially changed in cases of severe fever with thrombocytopenia syndrome virus (SFTSV) infection, and the inflammatory response probably plays an important role in disease progression. Angiotensin II is an important active substance of the renin-angiotensin system, and studies have demonstrated that angiotensin II is involved in key events in the inflammatory process and can regulate inflammatory cell responses.
Methods In order to elucidate the role of angiotensin II in the pathogenesis of SFTS, we collected serum samples from SFTS patients in the acute or convalescent phase and tested the angiotensin II levels using an enzyme-linked immunosorbent assay as well as SFTSV viral RNA with real-time reverse-transcriptase polymerase chain reaction. Furthermore, we explored possible correlations between the angiotensin II levels and clinical parameters in SFTS patients.
Results Our data showed that the serum level of angiotensin II was significantly increased in the acute phase compared with that seen in the convalescent phase and the healthy controls, while there were no significant differences between the convalescent cases and healthy controls (p>0.05). A correlation analysis demonstrated that the level of angiotensin II positively correlated with the SFTS viral RNA load. The angiotensin II levels were also found to be correlated with clinical parameters indicating impairments in organ functions. Moreover, we also found that the angiotensin II levels were significantly increased in the severe cases versus the non-severe cases (p<0.001).
Conclusion The serum angiotensin II levels in SFTS patients may be used to stratify the disease severity and are possibly predictive of disease outcomes.

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Objective We assessed the prevalence of sleep disordered breathing (SDB) and characteristics among patients who visited a urology clinic complaining of nocturia (URO group) and those who visited a sleep apnea (SA) clinic complaining of excessive daytime sleepiness (EDS) (SA group). Additionally, we evaluated the effects of continuous positive airway pressure (CPAP) therapy in the URO group patients with nocturia and SDB resistant to conventional therapy for nocturia.
Methods Questionnaires were used to assess EDS, nocturia and lower urinary tract symptoms in 34 URO group patients and 49 age-matched SA group patients. We also compared these factors in the male patients in both groups and the male and female patients in the SA group. Significant SDB was diagnosed as a 3% oxygen desaturation index (3%ODI) on pulse oximeter of >5/h. The treatment response was analyzed in six URO group patients treated with CPAP after not responding to the conventional medical treatment.
Results SDB was found in 91.8% of the SA group patients and 70.6% of the URO group patients. The level of EDS and lower urinary tract symptoms were similar in both groups. The SA group showed higher 3%ODI values, while the frequency of urination during bedtime was higher in the URO group. The frequency of nocturnal urination was reduced after CPAP in the subjects resistant to conventional therapy.
Conclusion SDB is as prevalent in patients who visit a urology clinic complaining of nocturia as in those who visit a sleep apnea clinic. Patients who complains of nocturia must be assessed for SDB before starting therapy for nocturia.

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The ingestion of raw seafood infected with nematode larvae of the Anisakidae family can lead to gastric anisakiasis. The majority of the infections involve a single larva, however, there have been instances of multiple infection. The incidence rate and the characteristics of multiple infection by Anisakis remain poorly understood. We herein present a case of parasitization by multiple Anisakis larvae and describe 14 cases of multiple parasitization representing the largest reported case series to date. Endoscopists should therefore be aware of the potential for multiple infection by Anisakis and the need for a thorough inspection of all parts of the stomach when encountering such cases.

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We herein report five cases of ulcerative colitis-associated cancer/dysplasia. Although clinical remission had been achieved in all patients, mucosal inflammation had been resolved in only one patient. Thus, in order to prevent cancer from developing, appropriate medical therapy aiming not only to relieve the clinical symptoms, but also to suppress chronic inflammation appears to be necessary. Moreover, cancer occurred as early as 4 years after the diagnosis in one patient. In patients without complete resolution of mucosal inflammation, careful surveillance colonoscopy should be initiated in the early phase.

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A 57-year-old man with a history of tuberculosis (TB) was found to have a pancreatic head mass, accompanied by stenosis of the common bile duct. Due to the inherent difficulty in differentiating pancreatic carcinoma from an inflammatory mass, endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) was thus performed. The pathological findings confirmed granuloma with caseous necrosis, and the results of the QuantiFERON TB2G test were positive. Accordingly, the patient was diagnosed with peripancreatic TB and thereafter was successfully treated with anti-TB therapy. Based on the findings of this case, we conclude that EUS-FNAB is a useful modality for the diagnosis of pancreatic TB.

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Whether a cardiac tumor is primary or metastatic strongly influences the therapeutic strategy. We herein present a case of a cardiac tumor that occupied most of the right atrium which required immediate treatment in a patient with breast cancer. Multiple imaging modalities, especially computed tomography and cardiac magnetic resonance imaging, provided a precise preoperative diagnosis. We performed cardiac surgery prior to breast cancer surgery because the cardiac tumor was thought to be a myxoma rather than a metastatic cancer.

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Congenital coronary artery fistulas (CAFs) are rare and asymptomatic, although symptomatic CAFs should be treated with percutaneous intervention or surgery. A 62-year-old woman developed bilateral coronary-to-pulmonary artery fistulas resulting in exertional chest pain. We herein report the successful use of trans-catheter closure of a coronary artery-to-pulmonary artery fistula, which lead to the coronary steal phenomenon, using an Amplatzer vascular plug with the trans-radial approach. After the procedure, the patient remained asymptomatic.

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A 38-year-old woman was admitted to our hospital because of amenorrhea, multiple bone fractures, and a Cushingoid appearance. Endocrinological investigations revealed that she had co-existing Cushing's disease and prolactinoma, with a serum level of prolactin (PRL) at 1,480 ng/mL, corticotropin (ACTH) at 81.3 pg/mL, and cortisol at 16.6 μg/dL. Due to the lack of indication for transsphenoidal surgery, cabergoline monotherapy was initiated. A 6-month course of treatment resulted in only subtle amelioration of hypercortisolism, while hyperprolactinemia was dramatically improved. In 5 cases of bihormonal (ACTH/PRL) pituitary macroadenoma reported in the English literature, 2 were initially treated with dopaminergic agonists with substantial effectiveness for both PRL and ACTH. We herein report an extremely rare case of bihormonal macroadenoma in which only PRL was responsive to treatment.

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We herein experienced 9 patients with primary thyroid lymphoma that developed during 3-18 years of ultrasonographic follow-up of Hashimoto's thyroiditis. All nine patients had localized mucosa-associated lymphoid tissue (MALT) lymphoma. Two patients had diffuse type, one had mixed type, and six had nodular type according to the ultrasonographic classification. A clearly enlarging goiter was observed before the diagnosis of lymphoma in 3 patients. An enlarging goiter was not apparent in the remaining 6 patients with nodular type lymphoma, however, the emergence or enlargement of a hypoechoic nodular lesion was observed. Thyroid MALT lymphoma may be diagnosed early by an ultrasonographic follow-up of Hashimoto's thyroiditis.

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We encountered a 62-year-old woman who experienced frequent episodes of hypoglycemia. She was diagnosed with postprandial reactive hypoglycemia according to the results of oral glucose and sucrose tolerance tests, having undergone an endocrinological examination and image inspection. The administration of low-dose voglibose, an alpha-glucosidase inhibitor (α-GI), improved the glucose fluctuations and inhibited hypoglycemic symptoms. Voglibose is also known to diminish oxidative stress and maintain endothelial function after hyperglycemia. An α-GI might effectively prevent hypoglycemic symptoms and endothelial dysfunction by suppressing oxidative stress in such cases.

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Uremic patients may have a variety of organ involvement, however, the precise causality may be impossible to determine in some cases because the symptoms of uremia are also associated with other diseases. With an emphasis on the elusive nature of uremia, we herein describe a 53-year-old man with preexisting renal impairment who developed acute pericarditis with deterioration of his renal function. Hemodialysis was immediately initiated on the presumption of uremia, however, articular symptoms emerged approximately a month later and led to a final diagnosis of rheumatoid arthritis, followed by successful withdrawal of hemodialysis.

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Hyponatremia is the most common electrolyte abnormality in clinical practice, and a differential diagnosis of the etiologic disorders is crucial because hyponatremia is associated with many different disease states including malignancies. Although only a few cases of hyponatremia with hepatocellular carcinoma (HCC) have been previously reported, the abnormal expression of arginine vasopressin (AVP) in tumor cells has not been demonstrated. We herein present a rare case of hyponatremia associated with the aberrant expression of AVP in tumor cells of HCC. This case suggests that an extensive diagnostic work-up is needed in patients with hyponatremia because hyponatremia may provide diagnostic clues for the presence of other underlying disorders.

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A 72-year-old Japanese woman was admitted to our hospital with rapidly progressive glomerulonephritis associated with anti-glomerular basement membrane antibody. Hemodialysis (HD) therapy was initiated on the day of admission using a biocompatible polysulfone (PS) membrane. Her platelet count (PLT; ×10⁴/μL) decreased gradually from 58.7 (day 1) to 5.8 (day 25). Considering the possibility of dialyzer-related thrombocytopenia (DRT), we measured her PLT count before and after the HD session on day 72, which revealed a dramatic decrease of 7.5 to 4.3. This finding suggested that the PS dialyzer caused PLT depletion. After discontinuation of the PS dialyzer, DRT was resolved.

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Clopidogrel was administered to a 67-year-old Japanese man to prevent the recurrence of cerebral infarction. Twelve weeks later, he was admitted to our hospital with acute renal failure, hemolytic anemia and thrombocytopenia, and was diagnosed with clopidogrel-induced thrombotic microangiopathy. Clopidogrel was immediately discontinued and corticosteroid and plasma exchange therapy were administered simultaneously. Thereafter, the patient's condition gradually improved. The patient had a decreased serum complement C3 level. This suggests that the activated alternative pathway is related to thrombotic microangiopathy (TMA). TMA is a critical drug-associated adverse reaction that clinicians should always be vigilant about, because clopidogrel is widely prescribed.

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An 80-year-old woman with rheumatoid arthritis and a past history of tuberculosis presented with exertional dyspnea and edema of both legs. Chest X-ray performed on admission showed bilateral pleural effusion. Thoracoscopy under local anesthesia was performed, and vasodilation and non-specific yellowish inflammatory changes were noted in the pleura. A pathological examination showed chronic fibrosing pleuritis in addition to chronic pleural inflammatory changes with lymphoid aggregates. The nails on all fingers and toes were thickened and displayed yellow discoloration, and the edema was resistant to diuretics. Lymphoscintigraphy was conducted, which showed lymphatic drainage abnormalities. The patient was ultimately diagnosed as having yellow nail syndrome.

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A 65-year-old woman was referred to our respiratory department because of incidentally detected endobronchial deposits. She had been diagnosed with Sjögren's syndrome 12 years earlier. Bronchoscopy showed protrusion of the reddened, shiny or edematous mucosa at the orifice of the lower lobe bronchus, suggesting a submucosal tumor. Based on the pathological findings of the transbronchial biopsied specimens, the patient was diagnosed with non-classified type tracheobronchial amyloidosis associated with Sjögren's syndrome, which was negative for both λ and κ chains, transthyretin and amyloid A. She has remained in good health without a relapse of the tumor.

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A 41-year-old woman was admitted due to a sudden-onset severe headache, left hemiparesis and dysarthria. Diffusion-weighted magnetic resonance imaging showed an acute infarct in the bilateral pons, and magnetic resonance angiography revealed basilar artery (BA) occlusion resulting from dissection of the right vertebral artery (VA). She was treated with intravenous recombinant tissue plasminogen activator (rt-PA) 110 minutes after symptom onset. Subsequently, brain angiography was performed along with mechanical thrombolysis using Trevo ProVue retriever devices. The BA was successfully recanalized 240 minutes after the onset of symptoms. Thrombectomy is a promising treatment strategy for cases of VA dissection resistant to intravenous rt-PA thrombolysis.

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Idiopathic intracranial hypertension (IIH) is a syndrome of increased intracranial pressure and presents as an intractable headache, vomiting, and ophthalmologic manifestations. We herein report the case of a young girl who presented with bilateral abducens nerve palsy due to IIH as the onset of systemic lupus erythematosus (SLE). The patient was successfully treated with corticosteroid therapy. Our case lacked the typical symptoms of IIH, such as headache or nausea; therefore, it is necessary to carefully determine the cause of bilateral abducens nerve palsies. The development of IIH in SLE patients is a rare occurrence, but this manifestation should not be overlooked.

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Cryptococcosis is a cosmopolitan but rare opportunistic mycosis which is usually caused by Cryptococcus neoformans. Although the most common and worrisome disease manifestation is meningoencephalitis, pulmonary cryptococcosis has the potential to be lethal. The diagnosis of cryptococcal pneumonia is challenging, given its non-specific clinical and radiographic features. Respiratory failure leading to acute respiratory distress syndrome as a consequence of cryptococcal disease has been infrequently addressed in the literature. We herein present a case of disseminated cryptococcal infection leading to acute respiratory distress syndrome, refractory shock, and multiorgan dysfunction as the initial clinical manifestation in a patient who was newly diagnosed with acquired immunodeficiency syndrome.

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A 64-year-old woman developed diarrhea after taking clindamycin for a dental infection. We diagnosed her with Clostridium difficile infection (CDI) and performed fecal microbiota transplantation (FMT) as the initial therapy using colonoscopy on an outpatient basis. The frequency of her bowel movements decreased from 10 times per day to two times per day three days after the procedure. The key component of FMT is to restructure the protective microbiome of the natural intestinal flora. We consider that FMT could be used as an effective first-line therapy for CDI if the efficacy and safety of this procedure is established in the future.

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We herein report a case of laryngeal Kaposi's sarcoma (KS) complicated by immune reconstitution inflammatory syndrome in a human immunodeficiency virus (HIV)-infected patient. The patient initially presented with KS involving the larynx, which was successfully treated with pegylated liposomal doxorubicin (PLD) and antiretroviral therapy (ART). PLD was discontinued after 2 courses because of a marked clinical improvement; however, the patient experienced progressive odynophagia and dyspnea 2 months after the initiation of ART. Laryngoscopy revealed a severely swollen, inflamed epiglottis. The readministration of PLD was successful, and the patient was thereafter discharged without any subsequent complications.

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Vibrio vulnificus infection often occurs in warm regions, frequently leading to necrotizing fasciitis, sepsis, and death. We herein report a rare case presenting in a cold climate region in northern Japan, Aomori district, of a V. vulnificus infection complicated by necrotizing fasciitis and septic shock. The patient's prior history of injury and typical clinical course were helpful clues to the diagnosis of V. vulnificus infection, and early initiation of antimicrobial treatment saved his life. V. vulnificus infection should be considered even in cold regions, particularly if patients have risk factors.

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Lactococcus garvieae is considered to be a rare pathogen with low virulence in humans. We herein experienced an unusual case of multi-valve infective endocarditis caused by L. garvieae in an elderly woman who had undergone bioprosthetic mitral valve replacement due to severe mitral stenosis with rheumatic etiology. The patient was successfully treated with cardiac surgery after teicoplanin antimicrobial therapy failure followed by ceftriaxone treatment. L. garvieae was confirmed as the pathogen through 16S rRNA sequencing. To the best of our knowledge, this is the first case to indicate an effective treatment for infective endocarditis caused by L. garvieae in the Republic of Korea.

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Kimura's disease (KD) is a rare lymphoproliferative inflammatory disorder, typically presenting as firm, painless or pruritic single or multiple subcutaneous lesions in the head and neck, especially in the parotid and submandibular regions. We herein report a case of a 39-year-old Japanese man presenting with a typical cephalocervical KD lesion around the salivary glands with a rare association with a distant subcutaneous mass at the hip. We also emphasize the radiologically and clinically important features in the differential diagnosis and management. To the best of our knowledge, this case is the first report of KD manifesting with a typical cephalocervical lesion and an atypical subcutaneous hip mass lesion.

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