Background Fistulas are a major complication of Crohn's disease (CD), but the treatment strategy for fistulizing Crohn's disease is controversial. The aim of this study is to analyze the efficacy of medical therapy for fistulizing Crohn's disease.
Methods Therapeutic regimens and clinical outcome of medical therapy were evaluated in 10 patients with fistulizing Crohn's disease (6 with external fistulas, 4 with internal fistulas). Complete response was defined as fistula closure with complete arrest of drainage in cases of external fistula, and disappearance of the fistula demonstrated by imaging studies in cases of internal fistula. Clinical remission was defined as a Crohn's disease activity index of less than 150 points.
Results Complete responses were observed in all 6 patients with external fistulas (4 patients treated with a combination of antibiotics and immunomodulators, and 2 also treated with infliximab). In contrast, fistula closure was observed in only 1 of 4 patients with internal fistulas. Clinical remission of CD was achieved in all patients with external fistulas, whereas there was no significant difference in the CD activity index before and after medical therapy in patients with internal fistulas.
Conclusions External fistulas were more responsive to medical therapy than internal fistulas in patients with CD. Combined treatment with antibiotics and immunomodulators might be a suitable initial therapy for CD patients with external fistulas, and infliximab can be used as an additional therapy in cases refractory to this combination therapy. However, randomized controlled studies will be required to investigate what kinds of therapies are optimal for CD patients with fistulas.

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Background The sirolimus-eluting stent (SES) has dramatically reduced the rate of restenosis in comparison to that with the bare-metal stent (BMS). In previous studies, the minimal luminal diameter (MLD) of lesions treated with a BMS was shown to improve from 6 months to 1 year.
Methods To evaluate 6-month and 1-year outcomes, angiographic follow-up data were analyzed for 285 patients (451 lesions) who underwent successful SES implantation compared to follow-up data for 2,561 patients (3,367 lesions) who underwent BMS implantation.
Results Angiographic follow-up was performed at 6 months for 396 SES-treated lesions and 2,628 BMS-treated lesions and at 1 year for 322 SES-treated lesions and 1,540 BMS-treated lesions. The 6-month angiographic restenosis rate was significantly lower for SES-treated lesions than for BMS-treated lesions (4.8% vs. 23.4%, p<0.01). From immediately after stent implantation to 6 months, quantitative coronary angiography revealed a significantly larger decrease in MLD of BMS-treated lesions than in MLD of SES-treated lesions (p<0.01). In BMS-treated lesions in which repeat revascularization was not performed at 6 months, MLD increased significantly from 2.08±0.63 mm at 6 months to 2.11±0.61 mm at 1 year (p<0.01). In SES-treated lesions, however, MLD decreased significantly from 2.55±0.56 mm at 6 months to 2.44±0.61 mm at 1 year (p<0.05).
Conclusions From 6 months to 1 year, stenosis of BMS-treated lesions regressed, but stenosis of SES-treated lesions progressed.

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Objective To determine the characteristics of thyroid nodules by using fine needle aspiration (FNA) biopsy and ultrasonography.
Patients and Methods FNAs of 1,004 patients with thyroid nodules between 2000 and 2007 were evaluated retrospectively. The surgical records of 101 of the patients were available and reviewed. The Odds ratios for nodule characteristics were calculated individually.
Results The sensitivity of FNA was 66.7% and the specifity was 95.2%. Positive predictive value was 72.7% and negative predictive value was 93.7%. Our diagnostic accuracy was 90.5%. Solitary nodules, irregular margins and microcalcifications were associated with increased risk of malignancy with Odds ratios 3.61 (95% CI: 1.25-10.42; p= 0,017); 5.44 (95% CI: 1.76-16.78; p= 0,003) and 39.29 (95% CI 8.32-185.47; p< 0.001) respectively. Macrocalcification, age, gender and thyroid status were not associated with increased risk of malignancy.
Conclusion Our data suggest that FNA is a reliable, reproducible and valid method to evaluate thyroid nodules and ultrasonographic features, especially microcalcification is a very important predictor of malignancy.

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Objectives Our study aimed to determine the frequency of sick euthyroid syndrome (SES) among patients diagnosed as non-small cell lung cancer (NSCLC) and its association with the stage of the disease, Karnofsky index (KI), and nutritional parameters.
Methods We enrolled 80 consecutive patients with newly diagnosed NSCLC. Cases with NSCLC were staged by using the TNM system. The cases were examined for thyroid function tests, KI and nutritional evaluation before treatment. Moreover, cases were investigated for their overall survival ratio.
Results Out of 80 patients, SES was identified in 28 (35%). SES was more frequent among stage III (26%) and stage IV (62%) cases. The body mass index (BMI), KI and serum albumin level were found to be significantly low in cases with SES when compared to cases without SES. SES was found to be negatively correlated with BMI, KI and serum albumin level, and it was positively correlated with disease stage and weight loss. Additionally, the presence of SES was found as a prognostic factor at survival analysis (p=0.0002).
Conclusion SES was frequently seen in cases with NSCLC. SES can be used as a predictor of poor prognosis in NSCLC patients.

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Objective This study evaluated the efficacy and safety of the formoterol Turbuhaler^® at dosages of 4.5, 9 and 18 μg bid compared with placebo in Japanese patients with COPD.
Methods In this randomized, double-blind, placebo-controlled, multicenter study, 36 patients with a pre-bronchodilator FEV₁ value within 40 to 70% of the predicted value were randomized to receive formoterol at doses of 4.5, 9, and 18 μg bid, and placebo, for 1 week in a crossover fashion.
Results The primary outcome variable, one hour post-dose FEV₁ on the last day of the one week treatment period, was significantly higher for all formoterol dosages compared with placebo (p<0.001 for all doses); adjusted g-means for formoterol 4.5, 9 and 18 μg bid, and placebo, were 1.510 L, 1.491 L, 1.520 L and 1.342 L, respectively. All three dosages of formoterol also provided significantly better improvements than placebo in the secondary variables FVC, inspiratory capacity (IC) and morning and evening PEF. Results for IC and PEF indicated a trend towards a larger improvement at higher dosages.
Conclusion Treatment with formoterol at dosages of 4.5, 9 and 18 μg bid showed significantly superior effects to placebo on FEV₁ in Japanese patients with COPD. The results for some of the secondary variables (IC and PEF) indicated a trend towards larger improvements at higher dosages. All dosages of formoterol were well tolerated in Japanese patients.

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Background Post-stroke depression (PSD) has a great impact on the quality of life of patients with stroke. The Mini International Neuropsychiatric Interview (MINI) and the Hamilton Depression Scale (HAM-D₁₇) are considered the most reliable diagnostic tests for depression. However, both are difficult to conduct in a clinical setting since they require completion of a questionnaire in a limited time period. The Japan Stroke Scale -Depression Scale- (JSS-D) was established by the Japan Stroke Society to evaluate mood disorders following stroke, including PSD. Here, we correlated the results of HAM-D₁₇, MINI and JSS-D scores.
Methods We studied 100 stroke patients (mean age: 64.6±11.6 [±SD], range: 32-85 years) in the subacute phase (2-5 weeks after onset). We determined the correlations between HAM-D₁₇ and JSS-D scores. We used MINI to diagnose PSD, which represented major and minor depression, and compared the results with those of JSS-D.
Results JSS-D scores correlated with those of HAM-D₁₇ (r=0.847, p <0.0001). The cutoff value of JSS-D score for PSD was 2.40. The sensitivity and specificity were 0.950 and 0.988, respectively.
Conclusion JSS-D is the most valuable diagnostic test for PSD based on its ease of use and reliability for estimating PSD in Japan.

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Objective This study was to clarify the neuropathological findings of non-herpetic acute limbic encephalitis (NHALE) and so-called acute juvenile female non-herpetic encephalitis (AJFNHE).
Methods We examined three rare autopsied cases consisting of probable one NHALE and two AJFNHLE. For comparison, we also studied 10 autopsied cases of hippocampal sclerosis mainly caused by anoxia.
Results In NHALE, neuronal loss with gliosis and microglia/macrophage infiltrations were mainly seen in the CA1 areas in the hippocampus. However, there were no apparent anoxic neuronal changes in the remaining neurons in the CA1, and astrocyte proliferations and microglia/macrophage infiltrations were also observed in the claustrum, while these were mildly present in the basal ganglia. In AJFNHE, pathological findings differed from those of NHALE with regard of the absence of limited pathology in the limbic system, microglia/macrophages widely infiltrated the brain including the hippocampal areas and mild lymphocytic infiltrations were observed in the subarachnoid spaces as well as in the parenchyma.
Conclusions The pathomechanism of NHALE and AJFNHE is obscure and autoimmune theory is proposed, however we must collect and examine many autopsied cases in order to clarify the pathomechanism.

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Objective We prospectively evaluated the usefulness of the QuantiFERON TB-2G (QFT-2G) compared to that of tuberculin skin test (TST) as a supportive method of diagnosing pulmonary tuberculosis (TB) without invasive examinations.
Methods The subjects were 90 patients who required differentiation of pulmonary TB clinically and for whom a definitive diagnosis could not be obtained after admission. The final clinical diagnosis of TB infection in 28 patients and non-TB infection in 62 patients was established using bronchoscopic procedures.
Results In patients with TB infection, the positive response rate on QFT-2G (79%) was significantly higher than that on TST (57%). The QFT-2G negative rate (5%) was significantly lower than that on TST (48%) in patients with non-TB infection. For QFT-2G test, there was a positive response in 25 patients, a negative response in 49, and indeterminate findings in 16. Of the two patients with a false-negative result on QFT-2G, one had pulmonary TB during immunosuppressive treatment and one had pulmonary tuberculoma. Of the three non-TB patients with a positive result on QFT-2G, two had pneumonia and one had pulmonary mycosis. Four TB patients with an indeterminate result on QFT-2G included two elderly patients and two immunocompromised patients.
Conclusions We could confirm the usefulness of the QFT-2G test compared to TST in patients requiring a differential diagnosis between pulmonary TB and other pulmonary diseases in this series. Therefore, we recommend the QFT-2G test as one of the useful noninvasive diagnostic examinations for pulmonary TB.

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Objective The aim of this study was to investigate the pathophysiology of hospital-acquired pneumonia (HAP) and the clinical efficacy of its first-line treatment and to examine the validity of "the Japanese Respiratory Society (JRS) Guidelines for management of HAP".
Methodology The observational survey was conducted during the period of June 2002-May 2004 and patients with HAP were prospectively surveyed using the consecutive enrollment method. A total of 1,356 patients from 254 hospitals nationwide were analyzed. Clinical response to first-line antibiotics was evaluated at the end of the medication.
Results The 30-day mortality rate was 19.8%. Patients were classified into four groups according to the JRS guideline criteria. There were remarkable variances in the number of cases of each group. Mild/moderate pneumonia with no risk factors (group I) accounted for 0.3% of all cases. The mortality rate tended to be higher, as clinical conditions became more serious (group II < III < IV). Alternatively, though categorized in the same group (group III), there was a difference in the mortality rate by the severity of pneumonia (severe cases 32.2% vs. moderate cases 11.0%). First-line medication using carbapenems accounted for 61.7% of total cases. The efficacy rate of guideline-concordant therapy was significantly higher than that of guideline-discordant therapy (54.2% vs. 41.7%).
Conclusions This is the first nationwide study on HAP in Japan. The clinical characteristics and prognosis of HAP were elucidated. Review of the current classification of the disease is required and these results provide valuable information for the next revision of the guidelines.

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We herein report a case of primary adenocarcinoma of the appendix, a very rare disease that is seldom diagnosed before surgical intervention. This case was first suspected for its unique colonoscopic presentation as a cecal submucosal tumor with an overlying mucin-coat at the appendiceal orifice. The diagnosis was later confirmed after the operation. The imaging features of this exceptional disease are presented in detail.

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We report a case of gastric hamartomatous inverted polyps that are a rare histological type of gastric polyp and difficult to diagnose. Gastric submucosal tumor was detected by upper gastrointestinal X-ray series in 37-year-old man. Endoscopy revealed a submucosal tumor (SMT) , which eroded with a depression on its surface in the fornix. Endoscopic ultrasonography showed a heterogeneous tumor in the third layer. Endoscopic submucosal dissection (ESD) was performed to resect the tumor completely. The pathological diagnosis was a gastric hamartomatous inverted polyp. The patient was later discharged without any complications. Hamartomatous inverted polyps without a stalk are classified as the SMT type because the tumor is inverted down growth into the submucosal layer, otherwise polyps with a stalk are classified as the polyp type. All of the polyps were resected endoscopically, however, surgical resection was performed for those of the SMT type, because it is difficult to remove this type completely by en-block resection using conventional EMR technique. ESD method may be indicated for SMT-type hamartomatous inverted polyps.

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This report describes a 92-year-old woman patient with patent ductus arteriosus (PDA). She seems to be the oldest patient with PDA hitherto reported in the medical history. She developed infective endocarditis (IE) and congestive heart failure, and died at the age of 92. At autopsy, the PDA was found to the left of the origin of the left subclavian artery. Both left and right ventricles were hypertrophied with markedly dilated pulmonary arteries. IE involving the aortic valve extended to the sinus of Valsalva and pericardium, inducing pericarditis and cardiac tamponade. IE also resulted in systemic septic embolization.

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A 75-year-old woman developed left ventricular apical ballooning, shortly after recovering from status epileptics. Plasma noradrenaline and adrenaline levels were 2.05 ng/ml and 0.48 ng/ml, respectively. Endomyocardial biopsy disclosed patchy areas of interstitial myocardial fibrosis, atrophy and vacuolization of cardiac myocytes, and some disappearance of myocyte nuclei. Follow-up echocardiography showed that the left ventricular apical ballooning was restored to normal within 25 days. These findings are compatible with neurogenic stunned myocardium. It is important to recognize that patients suffering from intractable seizures may harbor a risk of postictal catecholamine surge and catecholamine-induced myocardial dysfunction.

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We report an autopsied case of a 74-year-old man with primary pulmonary squamous cell carcinoma (SCC) associated with leukocytosis, hypercalcemia, phagocytosis in the bone marrow, reactive lymphadenopathy and mesangial cell proliferation in the glomerulus. Laboratory examination revealed increased serum levels of parathyroid hormone-related peptide (PTH-rP), granulocyte colony stimulating factor (G-CSF), interleukin-6 (IL-6) and soluble interleukin 2 receptor (s-IL2R). An autopsy showed moderately differentiated SCC at the left lower lobe of the lung, of which tumor cells distinctly showed cytoplasmic immunoreactivity to anti-G-CSF and anti-PTH-rP antibodies. Thus, pulmonary SCC seemed to produce both G-CSF and PTH-rP, causing leukocytosis, hypercalcemia, and IL-6 production from the bone. IL-6 also might have stimulated the proliferation of SCC and glomerular mesangial cells, and induced phagocytosis, reactive lymphadenopathy and hepatosplenomegaly by interacting with the mononuclear phagocytic system.

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A 38-year-old woman was admitted due to lymphangioleiomyomatosis (LAM)-associated massive chylous ascites and progressive cachexia. She was incidentally diagnosed to have ascites during her regular physical check-up two years previously and LAM was revealed as its underlying cause. Periodic paracentesis was required to ameliorate ascites-associated symptoms, but resulted in lymphocytopenia, malnutrition, and deterioration of general status. Ascites was refractory to diuretics and fat-restricted diet. Peritoneovenous shunt (Denver shunt^®) was placed and thereafter ascites has been managed successfully without any complications for one year after the placement. Peritoneovenous shunt should be considered in LAM patients whose chylous ascites can not be managed with conservative treatments.

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Tubulointerstitial involvement in the kidneys is frequently found but it is a less emphasized feature of lupus nephritis (LN). Recent studies have shown increases in the urinary excretion of β2-microglobulin (β2MG) and N-acetyl-beta-D-glucosaminidase (NAG), which are considered to indicate the presence of tubulointerstitial damage, particularly in cases of LN. However, the changes in these urinary parameters during the clinical course of LN have not yet been fully clarified. In this report, we describe the changes in the urinary excretion of β2MG and NAG during immunosuppressive treatment combined with double filtration plasmapheresis in a case of LN.

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Recently, great attention has been drawn to IgG4-related diseases such as autoimmune pancreatitis (AIP) sclerosing sialadenitis, retroperitoneum fibrosis, sclerosing cholangitis. IgG4-related diseases are characterized by high serum IgG4 concentrations, sclerosing inflammation with numerous IgG4-positive plasma cells, and steroid sensitivity irrespective of their organs of origin. In this report, we describe a case of nonspecific interstitial pneumonia, in which possible involvement of IgG4 was suggested. The patient was 59-year-old man, who was found to have bilateral interstitial pneumonia. Laboratory tests revealed that he had antinuclear antibody and a high serum IgG4 concentration. Pathological examination of the video-assisted thoracic surgery biopsy taken from the right lower lobe showed interstitial thickening associated with lymphoplasmacytic infiltration containing many IgG4-positive plasma cells. He was effectively treated by corticosteroid. The present case had many clinical and clinicopathologic similarities to systemic IgG4-related autoimmune disease. There have been no descriptions on isolated interstitial pneumonia with IgG4-positive plasma cell infiltration. This case suggested that IgG4-related disorders could also occur in the lung, and interstitial pneumonia may be a pulmonary manifestation of systemic IgG4-related autoimmune disease.

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Celiac disease is a risk factor for lymphoma. Previously, we reported a case of diffuse large B-cell lymphoma (DLBCL) associated with celiac disease in a Japanese patient. Without any signs of DLBCL recurrence, he suddenly developed gastrointestinal symptoms and subcutaneous masses after resuming a gluten-containing diet. Peripheral T-cell lymphoma (PTCL) was diagnosed. Although a complete response was seen for 8 months, he was later admitted again with pleural and pericardial effusion due to PTCL. Expression of cytotoxic molecules, CCR4 and CXCR4 were all confirmed in PTCL cells, and the patient died soon afterwards. Clinically speaking, even though no gastrointestinal symptoms were seen, a gluten-free diet should have been strongly recommended for this patient.

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A 52-year-old man was admitted to our hospital in October 2001 with abdominal pain. Abdominal X-ray indicated a diagnosis of ileus. Histopathological and immunological examination resulted in a diagnosis of immunoproliferative small intestinal disease (IPSID). He was treated with THP-COP therapy (pirarubicin, cyclophosphamide, vincristine, and prednisolone), which resulted in complete remission. Outpatient follow-up revealed hypoalbuminemia in May 2003 and upper gastrointestinal endoscopy showed duodenal mucosal nodularity. He was diagnosed with relapsed IPSID and salvage chemotherapy was started. Follow-up endoscopy confirmed that the therapy was effective, but uncovered another duodenal mucosal nodularity. Immunohistochemical staining revealed T-cell lymphoma. Chemotherapy was discontinued and the patient died in December 2004.

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We report an 18-year-old man with elevation of the creatine kinase (CK) level to 11,068 IU/L. There was no muscle atrophy or fat replacement on CT while muscles in the posterior compartment of lower legs showed high T2 signal intensity on MRI. We performed muscle biopsy from the gastrocnemius muscle. Immunohistochemical analysis demonstrated an absence of dysferlin leading to a diagnosis of preclinical dysferlinopathy. Typical distribution of muscle involvement was demonstrated not by CT but by MRI which may have contributed to facilitating diagnosing the earliest stage of preclinical dysferlinopathy, presenting with asymptomatic elevation of serum creatine kinase.

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A 32-year-old woman developed a headache, seizures, and stupor on postpartum day 8. An initial diagnosis of possible encephalitis was made considering the presence of fever, neck stiffness, and abnormal CSF findings. MRI demonstrated hyperintense signals consistent with bilateral borderzone areas. MRA showed severe proximal narrowing of anterior, middle, and posterior cerebral arteries bilaterally. The patient recovered completely over 2 weeks, and repeated MRI and MRA scans were normal. Reversible vasoconstrictions have been known to occur during puerperium, and the clinical symptoms of our patient resembled such cases. Prior reports attributed these cases of postpartum angiopathy to capillary leakage and edema resulting in leukoencephalopathy. Our case suggests reversible borderzone ischemia as an additional pathological process.

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The worldwide reemergence of tuberculosis is significant. In particular, the incidence of extrapulmonary tuberculosis is increasing. But tuberculous tenosynovitis is rare and may be overlooked as a cause of chronic tenosynovitis. Here, we present a case of a 24 year-old man with a mass lesion on the flexor side of the right wrist. Laboratory findings were generally negative, except for the acceleration of the erythrocyte sedimentation rate, and the tuberculosis skin test was strongly positive. Magnetic resonance imaging (MRI) of the mass lesion of the wrist revealed tenosynovitis. We performed open biopsy and mycobacterial cultures. Thus, we diagnosed the patient with tuberculous tenosynovitis. Tuberculous tenosynovitis is uncommon but should be kept in mind in cases of chronic tenosynovitis.

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We present a case of bacteremia caused by group G streptococci (GGS) and vertebral osteomyelitis in a homosexual man with amebic colitis. The organism likely entered the blood via the inflamed intestinal mucosa resulting from amebiasis. Arthritis of both hands, which probably represented poststreptococcal reactive arthritis, was also observed. We should be aware that diseases caused by GGS appear to be increasing in recent years, and a potential for serious infection exists with regard to GGS as well as group A streptococci.

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