The comorbidity of Crohn's disease (CD) and primary sclerosing cholangitis (PSC) is uncommon. Diagnosing such patients can be difficult, as illustrated by the following case. The combination of CD and PSC should be considered in patients with CD who have abnormal liver function. Because patients with PSC often present asymptomatically, all patients with CD should be screened for PSC by checking serum liver tests. Review of the literature suggests that there is an increased potential in these patients for the development of malignancy and long-term prognosis is poor. We conclude that patients diagnosed with a combination of CD and PSC should be managed with periodic colonoscopy, CA 19-9 investigation, early liver and bowel imaging, and liver biopsy. The treatment of CD associated with PSC remains unsatisfactory and the possibility of liver transplantation should be considered.

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Objective Elevated serum bilirubin concentrations protect from atherosclerotic diseases, however it is not clear whether or not higher serum bilirubin concentrations have the same effect in coronary artery disease (CAD). The brachial-ankle pulse wave velocity (baPWV) is a reproducible method to assess arterial stiffness. This study was aimed to investigate the relationship between serum total bilirubin (TB) and baPWV in patients with established CAD.
Methods We enrolled 638 patients (390 men, 248 women) with established CAD. TB was divided into tertiles. Simple and multiple linear regression analyses were used to assess the correlation between baPWV and TB.
Results The mean baPWV tended to decrease in men according to TB tertiles: Tertile 1=2,126.0, Tertile 2=1,832.5, and Tertile 3=1,692.5 cm/s. Likewise, the mean baPWV tended to decrease in women according to TB tertiles: Tertile 1=1,920.8, Tertile 2=1,829.0, and Tertile 3=1,701.3 cm/s. Univariate analysis showed that age, BMI, TB, ALT, GGT, Cho, SBP, DBP, UA, and TC were significantly associated with baPWV in men. In women, age, BMI, current smoker, Cho, SBP, DBP, UA, TC, TG, HDL-C, and LDL-C were significantly associated with baPWV. BMI, LnSBP, UA, TB, LnCho, and LnTC were correlated with baPWV in men in the multivariate model. However, only LnSBP, UA, and LnHDL-C were correlated with baPWV in women. TB was found to be a significant determinant for decreased baPWV only in men (β=-0.136; p<0.001).
Conclusion Our findings show that the level of total serum bilirubin is negatively correlated with arterial stiffness in men with established CAD.

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Objective Several studies have assessed the efficacy of angiotensin receptor blockers (ARBs) on peripheral insulin sensitivity using the euglycemic hyperinsulinemic clamp technique in hypertensive subjects. However, these subjects were mostly non-diabetic, and some studies showed that ARB treatment did not improve insulin sensitivity. Thus, it is still uncertain whether ARBs could improve insulin sensitivity in subjects with hypertension and diabetes. Therefore, we evaluated the effect of olmesartan on peripheral insulin sensitivity in subjects with type 2 diabetes and hypertension using M/I value during the euglycemic-hyperinsulinemic clamp technique.
Methods We enrolled 10 Japanese subjects with type 2 diabetes and hypertension who had never taken antihypertensive agents. Their blood pressure, fasting plasma glucose level, HbA1c and glucose utilization rate during euglycemic-hyperinsulinemic clamp (M/I value) were examined before and after 6 months of treatment with 10-20 mg/day olmesartan (mean: 13.0 mg/day).
Results Blood pressure decreased significantly from 156/88 mmHg before starting olmesartan to 135/76 mmHg after 6 months of olmesartan treatment. The mean M/I value increased significantly from 6.33±3.19 (mg/kg/min/mU/L) × 100 to 8.11±4.20 (mg/kg/min/mU/L) × 100. Peripheral insulin sensitivity improved in eight out of ten subjects. Fasting glucose levels and HbA1c levels also decreased significantly.
Conclusion These results indicate that olmesartan improves glucose metabolism by improving the peripheral insulin sensitivity in subjects with type 2 diabetes.

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Objective Phosphate binders are used in the treatment of hyperphosphatemia in peritoneal dialysis (PD) patients. An ideal phosphate binder for long-term use must be effective with little or no side effects. We evaluated the long-term efficacy and side effects of lanthanum carbonate (LaC) used in combination with other phosphate binders in PD patients.
Patients The subjects of this retrospective study were 30 PD patients who received LaC at Kyushu University. The effect of LaC on various biochemical parameters (serum phosphate, calcium and parathyroid hormone), daily dose of other phosphate binders, gastrointestinal side effects, and nutritional status were determined during the 24-week treatment. We also evaluated the rate of achievement of the Japanese Society of Dialysis Treatment guidelines for secondary hyperparathyroidism and used multivariate analysis to determine the factors associated with the efficacy of LaC.
Results LaC (960±412 mg/day) reduced serum phosphate from 6.2 to 5.3 mg/dL. The rate of achievement of the guideline target improved after 24 weeks of LaC treatment. The dose of other phosphate binders and dialysis volume remained unchanged during the treatment. Although 53% of patients experienced at least one gastrointestinal side effect, LaC treatment did not affect the nutritional status, and none of the patients discontinued LaC. Multivariate analysis identified low stature, old age and high baseline total creatinine clearance as significant factors that determine the effectiveness of LaC in PD patients.
Conclusion Low dose LaC treatment used in combination with other phosphate binders improved serum phosphate control with tolerable gastrointestinal symptoms in PD patients.

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Objective This is a retrospective study for risk assessment of acute kidney injury after allogeneic hematopoietic stem cell transplantation (allo HSCT) based on the Acute Kidney Injury Network (AKIN) criteria.
Methods Two hundred and eighty-nine consecutive patients who received allo HSCT were studied retrospectively to identify the risk factors for AKI according to the AKIN criteria. The incidence of AKI based on AKIN staging and overall survival (OS) was evaluated using Cox proportional hazard regression models treating each AKIN stage as a time-dependent covariate.
Patients We identified a total of 180 patients who developed AKI within 100 days after allo HSCT; AKI was classified as stage 1 in 88 patients (30.5%), stage 2 in 46 patients (15.9%) and stage 3 in 46 patients (15.9%).
Results Patients who developed stage 3 AKI had a significantly worse survival compared to those who developed no AKI or lower stage AKI (HR: 7.6, 95%CI: 4.8-12.1; p<0.001). Multivariate analysis for risks for developing AKI revealed an episode of sepsis or sinusoidal obstruction syndrome (SOS) and the use of liposomal amphotericin as a major cause of the severe stage of AKI.
Conclusion On the basis of our analysis, sepsis, hemorrhagic cystitis, and acute GVHD were associated with severe AKI, and SOS was associated any stage of AKI.

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Objective Silent cerebral infarction (SCI) and increased carotid intima-media thickness (IMT) have been found to be associated with future stroke in the general population. We investigated whether a combination of SCI and increased IMT is a predictor of cardiovascular events and all-cause mortality in chronic hemodialysis (HD) patients.
Methods We performed a retrospective cohort study of 70 HD patients who had one or more risk factors for atherosclerosis but no history of cardiovascular disease. We performed cranial magnetic resonance imaging (MRI) and measured carotid IMT at baseline, and then evaluated the risks of cardiovascular events and all-cause mortality by using Cox proportional hazards models. The Kaplan-Meier method and a log-rank test were used to compare event-free survival.
Results SCI was present in 25 patients (35.7%) at baseline. During an average follow-up of 46.3±14.3 months (range: 19 to 56 months), 15 patients (21.4%) died and 16 (22.9%) experienced a new cardiovascular event. The presence of SCI in combination with increased carotid IMT at baseline was independently associated with cardiovascular events and all-cause mortality after adjustment for age, sex, duration of dialysis, and traditional vascular risk factors.
Conclusion SCI, similar to carotid IMT, is an independent predictor of cardiovascular events and all-cause mortality in chronic HD patients.

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Objective The aim of this study is to propose the cutoff level of waist circumference (WC) on the basis of homeostasis model assessment of insulin resistance (HOMA-IR) levels in order to diagnose metabolic syndrome (MetS).
Methods We examined a total of 798 non-diabetic men (40-65 years of age) by using a receiver operating characteristic (ROC) curve to determine the cutoff level that yielded the maximum sensitivity plus specificity. According to the criteria proposed by the International Diabetes Federation (IDF), and the Japanese Society of Internal Medicine (JSIM), subjects with ≥2 metabolic components other than abdominal obesity, were considered to have MetS.
Results The overall prevalence rates of IDF- and JSIM-MetS were 17.4% (n=139) and 15.5% (n=124), respectively. The median levels of WC and HOMA-IR were 83.1 [interquartile range (IQR): 78.5-88.4] cm and 0.84 (IQR: 0.61-1.19), respectively. HOMA-IR was highly correlated with each metabolic parameter (each p<0.05), and in addition, multiple linear regression analysis of HOMA-IR (adjusted R²=0.459) showed that WC level was the strongest independent predictors of HOMA-IR level (F=141.1, p<0.05). According to ROC curve analysis, the cutoff level of HOMA-IR for predicting IDF- and JSIM-MetS was 0.92 for both (sensitivity: 79.9% and 78.2%, specificity: 64.9% and 63.6%). Based on the HOMA-IR level, the proposed WC cutoff level was 82.7 cm (sensitivity: 75.4%, specificity: 63.8%).
Conclusion This study suggests that WC level should be more strictly managed than current criteria, for preventing the development of MetS in non-diabetic middle-aged Japanese men.

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Behçet's disease is a chronic relapsing disease with multiple organ system involvement, including the gastrointestinal tract, which is known as intestinal Behçet's disease. Intestinal Behçet's disease is often resistant to empirical treatments such as 5-aminosalicylic acid, immunomodulators and steroids and often causes a perforation, requiring surgical resection. Therefore, intestinal lesions are considered to be a poor prognostic factor in Behçet's disease. Recently, several reports have demonstrated the efficacy of anti-TNFα monoclonal antibodies, such as infliximab, against intestinal Behçet's disease, however, it remains unknown whether anti-TNFα therapy can improve the prognosis of patients with intestinal Behçet's disease. We herein report the case of an adult female patient with intestinal Behçet's disease who responded well to the induction therapy with infliximab, and has been maintained in remission by scheduled administration of infliximab. Her C-reactive protein level has been sustained at a negative level, and endoscopic findings revealed complete mucosal healing. Therefore, infliximab may have the potential to induce "sustained deep remission" in patients with intestinal Behçet's disease.

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Mutations in the SLC25A13 gene lead to neonatal intrahepatic cholestasis caused by citrin deficiency and/or adult-onset type II citrullinemia (CTLN2). A 62-year-old man presented with recurrent episodes of neuropsychiatric manifestations. On admission, he had disorientation and flapping tremor. Laboratory data showed hyperferritinemia in addition to postprandial hyperammonemia and citrullinemia. A liver biopsy specimen revealed moderate hemosiderin deposits and hepatocytes with macrovesicular fat droplets. Genetic analysis of the SLC25A13 gene identified the previously reported p.S225X mutation and a novel p.D493G mutation. Hyperferritinemia might also be a characteristic finding of CTLN2-related fatty changes of the liver.

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Autoimmune pancreatitis (AIP) is characterized by irregular narrowing of the main pancreatic duct (MPD), and narrowing of the MPD is an essential criterion for the diagnosis of focal/segmental AIP according to the Japanese diagnostic criteria 2011. We report a 55-year-old man in whom magnetic resonance imaging showed two masses in the pancreatic head and tail and whose pancreatogram was normal at first. However, the two masses changed into diffuse swelling of the pancreas, and diffuse narrowing of the MPD appeared after the cessation of steroid therapy. Finally, we could diagnose this patient as having AIP according to the Japanese diagnostic criteria.

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Here, we report an elderly man with acute-on-chronic hepatitis accompanied by massive ascites. He showed elevated serum transaminase and anti-nuclear antibody (ANA) levels. Liver biopsy showed diffuse multinucleated giant hepatocytes with interface hepatitis, and he recovered with administration of azathioprine in addition to corticosteroids. Follow-up liver biopsy after recovery showed improvement of hepatic inflammation and reduction of giant hepatocyte formation. The patient is receiving low-dose corticosteroid maintenance therapy and he has remained healthy for 8 years to date. Active immunosuppressive treatment may be beneficial in patients with adult syncitial giant cell hepatitis (AGCH).

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A 74-year-old woman had an undifferentiated carcinoma with osteoclast-like giant cells (UCWOGC) in the body of the pancreas with massive portal vein tumor thrombus (PVTT). Because the PVTT progressed so rapidly into the right portal branch, the patient first underwent distal pancreatectomy and tumor thrombectomy to prevent life-threatening portal venous obstruction. Although a recurrent PVTT had developed early postoperatively, systemic gemcitabine treatment was so effective that it induced complete remission 5 months after the initiation of chemotherapy. The patient continued to be in complete response for 12 months, and has survived for 19 months since surgery.

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Branched-chain amino acid (BCAA) supplements have mainly been administered as a nutritional intervention for decompensated liver cirrhosis. Several studies have shown that short-term BCAA supplementation improves insulin and glucose tolerance in patients with liver cirrhosis. However, the long-term effects of BCAA supplementation on glucose tolerance and in patients with nonalcoholic steatohepatitis (NASH)-related liver cirrhosis are unknown. Herein, we report 2 cases of NASH-related liver cirrhosis in which long-term BCAA supplementation improved glycemic control. We conclude that in the absence of an effective conventional therapy for NASH-related liver cirrhosis, BCAA supplementation should be considered as an alternative treatment.

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Herein we report a 57-year-old man with lower extremity edema and swelling in the scrotum who was found to have a periaortic soft tissue mass and hydronephrosis by computed tomography. With the most plausible diagnosis of retroperitoneal fibrosis, corticosteroid therapy was initiated; however, it did not improve his symptoms. Upper gastroscopy performed on day 20 post admission showed ulcerative regions with an irregular border and fusion of thickened rugae at the gastric angle; the diagnosis of gastric adenocarcinoma was confirmed histologically. It is important to always be aware of unrecognized malignancies that are accompanied by retroperitoneal fibrosis.

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Kounis syndrome has been known as allergenic angina and/or allergenic myocardial infarction following an allergic reaction. Probable allergic insults usually include drugs, latex, and food. Although ceftriaxone administration has been associated with various allergic reactions such as urticaria, angioedema, erythema, rash and anaphylactic shock, as far as we know, there is no published report that has shown an association between ceftriaxone use and Kounis syndrome. Here, we describe the first report of allergic vasospasm, culminating in acute inferior myocardial infarction, probably as the result of an acute allergenic reaction, after ceftriaxone use.

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A 70-year-old man complained of right leg swelling due to right iliac vein stenosis. No mass was identified around the stenotic site, and the vessel wall had not become thickened. Self-expandable stents were positioned at the stenotic site. About two years later, chest CT revealed lung nodules. Pathology showed sarcoma. A mass that was considered to be the primary lesion was found around the stent in the right iliac vein. Although sarcoma of the iliac vein is very rare, it should be considered in the differential diagnosis of iliac vein stenosis, even if there are no suspicious findings from image studies.

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Kawasaki disease (KD) is a mucocutaneous lymph node syndrome with important cardiovascular complications which usually afflicts young children. We describe a 16-year-old woman who developed transient heart failure during the acute phase of incomplete KD. The diagnosis was based on the development of coronary aneurysms during heart failure and 2 criteria of the disease. Incomplete KD is a cause, albeit rare, of myocardial dysfunction in human adolescents. Healthcare providers should therefore be aware of the possibility of incomplete KD in patients with heart failure during the course of an acute febrile illness associated with mucocutaneous changes.

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A 58-year-old woman was admitted due to visual field abnormalities, thirst, polydipsia, polyuria and fever. T1-weighted magnetic resonance imaging revealed an absence of the usual bright signal in the posterior lobe of the pituitary gland, and an enlarged pituitary gland with a thickened stalk was enhanced by the gadolinium contrast medium. Computed tomography revealed tumor lesions in the left maxillary sinus and right retroperitoneum and axillary and subclavian lymph node swelling. An endocrinological provocation test demonstrated that her pituitary endocrine function was disturbed, although her ACTH and TSH secretion was normal. The patient was histologically diagnosed with neurosarcoidosis accompanied by hypopituitarism and central diabetes insipidus upon an examination of a subclavian lymph node specimen. Six months of prednisolone treatment resulted in the disappearance of any morphological abnormalities in the pituitary gland and stalk as well as a partial improvement in her LH, FSH and GH secretions. Pituitary endocrine functions can be rescued if steroid treatment is performed under conditions that maintain several hormonal axes.

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A 57-year-old Japanese man presented with drug-resistant hypertension without Cushingoid features. Endocrinological tests revealed autonomous secretion of cortisol with suppressed plasma adrenocorticotropic hormone (ACTH). Imaging examinations showed multiple macronodules in the bilateral adrenal gland. These findings were consistent with subclinical Cushing's syndrome caused by ACTH-independent macronodular adrenal hyperplasia (AIMAH). Left adrenalectomy was performed and the resected adrenal lesion was consistent with the pathological diagnosis of AIMAH. Furthermore, in resected tissue, we demonstrated intraadrenal production of ACTH by immunohistochemical analysis and RIA. This is a very rare case of AIMAH showing ectopic production of ACTH, which may be associated with autonomous cortisol secretion.

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Agranulocytosis is a rare adverse effect of methimazole. The usual duration of treatment prior to the onset of agranulocytosis is approximately 1 to 4 months, and can be as long as 1 year. Agranulocytosis together with hepatotoxicity is an extremely rare idiosyncratic side effect of methimazole treatment. We present an unprecedented case of a Grave's disease patient who showed a strong reaction to methimazole with obvious agranulocytosis and hepatotoxicity which developed only six days after administration. This case, along with a literature review, is offered with the aim to increase the awareness of physicians of sudden onset agranulocytosis and hepatotoxicity from methimazole.

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Renal tumor metastasis from thyroid follicular carcinoma is very rare. Here, we present a 64-year-old woman with metastatic thyroid follicular carcinoma presenting as a primary renal tumor. The renal tumor was removed and revealed the origin of thyroid follicular carcinoma. Six months after the treatment of renal tumor, the patient was readmitted for the enlarged thyroid gland. The follicular carcinoma was revealed in the resected thyroid gland. The serum thyroglobulin level and thyroid function tests were consistently normal. Although with metastasis to the kidney, thyroid follicular carcinoma is thought to have a good prognosis.

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The prevalence of postinfectious glomerulonephritis has decreased in most developed countries. We report the case of a previously healthy, immunocompetent 65-year-old woman who developed acute glomerulonephritis associated with human parvovirus B19 infection. She was referred by her primary care physician for suspected congestive heart failure but she had an elevated creatinine level and an abnormal urinalysis. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis. After biopsy, we learned that she had been in frequent contact with her grandson who had been diagnosed with erythema infectiosum. Her human parvovirus B19 serum IgM titer was elevated at 3.50, indicating current infection.

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A 25-year-old woman with no underlying disease presented with a large fluid-filled cavitary lesion in the right lung. Mycobacterium celatum was isolated from the cavitary fluid, and treatment with ethambutol, rifampicin, and clarithromycin was initiated. After 4 months of treatment, right lower pulmonary lobectomy was performed. Histological examination confirmed M. celatum infection as well as concurrent congenital cystic adenomatoid malformation (CCAM). M. celatum has been implicated in opportunistic infections. This infection, however, was related to underlying CCAM, which resulted in a large cavitary lesion. CCAM diagnosed in adulthood is rare, and is made more challenging by an infectious complication.

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We present a 56-year-old woman with acute promyelocytic leukemia (APL) complicated with serious chronic subdural hematoma at presentation. She was treated with urgent hematoma evacuation and subsequent prompt chemotherapy, with administration of platelets and fresh frozen plasma. After six weeks, she achieved hematological complete remission. Thereafter she received three courses of conventional consolidation chemotherapy and achieved molecular remission. Even under conditions of severe coagulatory disturbance, aggressive therapeutic intervention including surgical procedures can save the life of a patient suffering from simultaneous APL and fatal subdural hematoma at presentation.

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We report a 74-year-old woman who presented with recurrent isolated abducens nerve paresis. Cranial magnetic resonance imaging revealed that the right abducens nerve was sandwiched between the right internal carotid artery and a persistent trigeminal artery (PTA) variant, which might have led to neurovascular compression of the abducens nerve, resulting in abducens nerve damage. Normal variants of PTA, which are cerebellar arteries originating from a precavernous portion of the internal carotid artery, must be carefully observed as such variants can potentially cause a neurovascular compression of the abducens nerve.

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A 71-year-old man with hyperlipidemia abruptly developed left-sided isolated shoulder palsy. Cranial magnetic resonance imaging demonstrated infarction of the cortical branch of the right middle cerebral artery (MCA). In the primary motor cortex, there is broad somatotopic representation of various body parts in a particular arrangement, and the area corresponding to the shoulder is very small. Consequently, there have been only 3 reported cases of isolated shoulder palsy due to cerebral infarction, and its vascular supply remains uncertain. The present case indicates that the corresponding area to the shoulder receives its blood from the cortical branch of the MCA.

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Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited neurodegenerative disorder with symptoms of spastic ataxia, neuropathy, pyramidal sign, finger and foot deformities, and hypermyelination of retinal nerve fibers. SACS is mutated in ARSACS. The clinical diversity of ARSACS is recognized, which sometimes makes its diagnosis difficult. By using homozygosity mapping, we identified a novel homozygous c.12020C > T missense mutation in a consanguineous Japanese family with atypical clinical features. In addition to the absence of spasticity and hypermyelinated retinal nerve fibers, the present case had urinary dysfunction, impotence, and severe constipation, indicating the possibility of autonomic dysfunction. Furthermore, we showed the diagnostic usefulness of MRI even for the case of atypical clinical features. It had been considered that cases without obvious spasticity were very rare, however recent reports on atypical cases as well as our case indicate that ARSACS cases without obvious spasticity might be more frequent than previously thought. We should be aware of atypical features of ARSACS for the correct diagnosis.

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Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is a rare complication of pregnancy. The mortality rate associated with HELLP syndrome increases when life-threatening complications occur. A 37-year-old woman at 37 weeks of gestation developed severe cerebral hemorrhage at the beginning of labor induction and was transferred to our hospital, where HELLP syndrome was diagnosed. She developed disseminated intravascular coagulation (DIC), hepatic hematoma, and cerebral infarction after surgery. On day 68, she was transferred to her local hospital. Careful observation and rapid management can save patients with severe complications of HELLP syndrome.

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Severe hypomagnesemia is a serious clinical condition. Proton pump inhibitor (PPI) induced hypomagnesemia has been recognized since 2006. In March 2011 the U.S. Food and Drug Administration advised that long-term use of PPI can induce hypomagnesemia. We report the first Japanese case of hypomagnesemia associated with chronic use of PPIs in a 64-year-old man hospitalized for nausea, bilateral ankle arthritis, and tremor of the extremities who had convulsions 3 days after admission. Blood analysis showed severe hypomagnesemia. He had been taking rabeprazole (10 mg/day) for 5 years. After stopping rabeprazole and correcting the electrolytes imbalances, his symptoms improved without recurrence.

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Idiopathic segmental infarction of the greater omentum (ISIGO) is a rare cause of acute abdomen. We report a case of ISIGO triggered by a unique etiology-wearing tight pants. A 75-year-old woman presented with acute lower abdominal and left flank pain with rebound tenderness. Her abdominal wall had a linear circumferential scar, which was compatible with a history of a tight elastic waistband of her pants weared around her waist. A computed tomographic (CT) scan showed a lesion of heterogeneous density located distal to the abdominal wall constriction. She was treated conservatively. Thus, combining the physical examination and CT findings is important for the diagnosis of ISIGO.

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We herein describe the case of a 25-year-old woman who suffered from atypical familial Mediterranean fever for more than a decade. She presented with a periodic fever, abdominal pain and persistent ulcers in the terminal ileum. Colchicine was effective, and familial Mediterranean fever was diagnosed. A genetic study showed a heterozygous E148Q mutation in the MEFV gene. Multiple, recurrent, abscess-like lesions developed asynchronously in the spleen, liver, and a lung. Infliximab was administered when colchicine treatment became ineffective. However, infliximab treatment soon became ineffective, probably because antibodies were generated against it. Therefore, etanercept treatment was started, and the patient showed an immediate response.

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