Preoperative routine evaluation of bilateral adrenal glands by endoscopic ultrasound and fine-needle aspiration in patients with potentially resectable lung cancer.

BACKGROUND AND STUDY AIMS: The aim of the current study was to assess the detection rate of the right adrenal gland and the diagnostic ability of endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) for the diagnosis of adrenal metastasis in potentially resectable lung cancer. PATIENTS AND METHODS: This retrospective cohort study included a consecutive series of 150 patients undergoing EUS/EUS - FNA for staging of lung cancer. The detection rate of the right adrenal gland by EUS and the diagnostic accuracies of computed tomography (CT), positron emission tomography-CT (PET-CT), and EUS/EUS - FNA for the diagnosis of adrenal metastasis were evaluated. RESULTS: The right adrenal gland was visualized by EUS in 131 patients (87.3 %); the left adrenal gland was visualized in all patients. Findings suggestive of metastasis in either one of the adrenal glands or in both were observed in 6 patients (4.0 %) by CT, in 5 patients (3.3 %) by PET-CT, and in 11 patients (7.3 %) by EUS. EUS - FNA was performed simultaneously in the 11 patients, and in 4 patients the diagnosis of metastasis was established. The accuracy for the diagnosis of adrenal metastasis was 100 % for EUS/EUS - FNA, 96.0 % for CT, and 97.0 % for PET-CT (P = 0.1146). CONCLUSIONS: As well as the left adrenal gland, the right adrenal gland was also usually visible by EUS. EUS/EUS - FNA provided an accurate diagnosis of adrenal metastasis, although the prevalence of adrenal metastasis was relatively low in these patients with potentially resectable lung cancer.

Combined endobronchial and endoscopic ultrasound-guided fine needle aspiration for mediastinal nodal staging of lung cancer.

BACKGROUND: Recently, transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been evaluated for mediastinal nodal staging (N staging) of lung cancer, as this technique is less invasive than mediastinoscopy and possibly more accurate than 18F-fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT). However, EUS-FNA does not provide access to pretracheal and hilar lymph nodes. More recently, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been introduced as a novel technique for accessing pretracheal and hilar lymph nodes. Although the combined endoscopic approach of EUS-FNA and EBUS-TBNA is presumably more accurate than PET-CT, only a few reports have quantitatively evaluated its diagnostic ability. Therefore, we prospectively assessed the diagnostic yield of this combined endoscopic approach for mediastinal N staging of lung cancer. METHODS: A consecutive series of 120 patients with suspected resectable lung cancer on CT findings underwent PET-CT and combined EUS-FNA/EBUS-TBNA. The accuracy and other diagnostic indices of the combined approach in mediastinal N staging were compared with those of PET-CT. RESULTS: Among the enrolled patients, a final pathological N stage was established in 110 patients. The accuracy of the combined approach using EUS-FNA and EBUS-TBNA was significantly higher than that of PET-CT (90.0 % vs. 73.6 %; P < 0.0001). The sensitivity, specificity, and positive and negative predictive values were respectively 71.8 %, 100 %, 100 %, and 86.6 % for the combined approach vs. 47.4 %, 87.5 %, 66.7 %, and 75.9 % for PET-CT. CONCLUSIONS: The combined endoscopic approach using EUS-FNA and EBUS-TBNA provided excellent diagnostic performance. Therefore, this approach is strongly recommended before surgery or mediastinoscopy to avoid futile thoracotomy and surgical intervention.

Carbon dioxide insufflation vs. conventional saline irrigation for peroral video cholangioscopy.

BACKGROUND AND STUDY AIMS: Recent studies have evaluated the efficacy of peroral cholangioscopy (POCS) for diagnosis of biliary diseases. In order to obtain clear images with POCS, saline irrigation, which is performed to replace yellow bile, is carried out for an extended duration. The aim of this study was to evaluate the feasibility of replacing saline irrigation with CO2 insufflation during POCS. PATIENTS AND METHODS: A total of 36 patients who had bile duct lesions and were due to undergo POCS were enrolled in the study. Of these patients, 18 underwent POCS using saline irrigation followed by CO2 insufflation, and 18 patients underwent the reverse approach. The two methods were compared with regard to the time required to obtain a clear endoscopic image and the quality of the images. RESULTS: The median time required to obtain a clear endoscopic image using CO2 insufflation (5.0 min) was significantly shorter than that required for saline irrigation (22.5 min; P < 0.001). The quality of the endoscopic images obtained was similar in 27 cases. However, CO2 insufflation provided better images in four cases that showed an abundance of mucin or biliary sludge, and saline irrigation was superior to CO2 insufflation in five cases that showed severe stricture with bleeding and tall papillary lesions. CONCLUSIONS: CO2 insufflation during POCS can reduce procedure time and simplify cholangioscopy. The overall image quality was similar to that obtained with conventional saline irrigation.

"Transmural air leak": a computed tomographic finding following endoscopic submucosal dissection of gastric tumors.

BACKGROUND AND STUDY AIMS: A small amount of free air, visible on CT but not on plain chest radiography, which appeared following endoscopic submucosal dissection (ESD) of a gastric neoplasm without endoscopically visible perforation, was defined as a "transmural air leak", and a prospective, consecutive entry study was performed to determine its incidence and clinical significance. PATIENTS AND METHODS: Between January 2006 and September 2008, ESD was performed for 246 gastric lesions in 246 consecutive patients. Abdominal CT scan was performed 1 day after ESD. In addition, chest radiography and blood biochemistry tests were performed at different time points before and after ESD. RESULTS: Two hundred and nineteen lesions (89 %) were curatively removed by ESD. Among the total of 246 patients, we encountered endoscopically visible perforation during ESD in 2 patients (0.8 %), and clinically suspected perforation diagnosed by the presence of free air on chest radiography but invisible during ESD in 3 patients (1 %), while transmural air leak was observed in another 33 (13 %). Air leak occurred in cases where resection size was larger, procedure time longer, and the muscularis propria on the ulcer base was exposed at the end of ESD. Patients with air leaks developed pyrexia at a higher rate than those without (36 % vs. 16 %, P = 0.018). These patients recovered with antibiotics and required no endoscopic or surgical intervention. The presence of an air leak did not affect the duration of hospital stay. CONCLUSIONS: A transmural air leak was observed in 13 % of the patients undergoing ESD. Larger resection size, prolonged procedure time, and exposure of the muscularis propria on the ulcer base were risk factors for transmural air leak, but the outcome of patients with this complication was good.

Clinical trial: extended treatment duration of peginterferon-alpha2b plus ribavirin for 72 and 96 weeks in hepatitis C genotype 1-infected late responders.

BACKGROUND: The benefits of prolonging peginterferon and ribavirin after 48 weeks of treatment to maximize sustained virological responses (SVR) in hepatitis C virus (HCV) genotype 1-infected patients remain to be understood. AIM: To investigate whether extended treatment longer than 72 weeks may be superior to 72-week treatment. METHODS: A total of 120 treatment-naïve or retreated patients with HCV genotype 1 were treated with peginterferon-alpha-2b (1.5 microg/kg/week) plus weight-based ribavirin. We had 34 late responders, in whom HCV RNA first became undetectable at week 12-48, and randomized them into three groups receiving standard-dose peginterferon-alpha-2b plus low-dose ribavirin (200 mg/day) for extended 24 weeks (group A), receiving low-dose peginterferon-alpha-2b (0.75 microg/kg/week) plus low-dose ribavirin for extended 48 weeks (group B) or no extended treatment (group C), and evaluated the outcome according to their virological response. RESULTS: Multivariate analysis showed that the treatment for 96 weeks was identified as a significant, independent factor associated with SVR in HCV genotype 1-infected late responders in comparison with group A [odds ratio (OR), 10.002; P = 0.080] and group C (OR, 17.748; P = 0.025). CONCLUSION: Extending the treatment duration from 48 weeks to 96 weeks improves SVR rates in genotype 1-infected patients with late virological response to peginterferon-alpha-2b and ribavirin.

Endoscopic ultrasound-guided fine needle aspiration biopsy for splenic tumor: a case series.

Splenic tumors are occasionally found in clinical practice but the diagnosis is often difficult if only serologic and imaging tests are used. Therefore, pathologic sampling is required in such cases. Endoscopic ultrasonography (EUS) provides a good image of the spleen through the gastric wall, and a transgastric EUS-guided fine needle aspiration (EUS-FNA) biopsy may be easier than the percutaneous approach. Furthermore, a large-gauge needle may raise the capability of EUS-FNA for the histopathologic diagnosis. The aim of this study was to evaluate the yield of EUS-FNA using a large-gauge needle for a splenic tumor. Five patients with splenic tumor were subjected to EUS-FNA with a 19-gauge needle to obtain histopathologic materials. A pathologic sample was obtained in all cases, and the diagnoses were lymphoma (n = 2), sarcoidosis (n = 2), and inflammatory pseudotumor (n = 1). EUS-FNA using a 19-gauge needle is safe and useful for the diagnosis of splenic tumors.

Detection of Pb-LIII edge XANES spectra of urban atmospheric particles combined with simple acid extraction.

Pb-LIII edge XANES spectra of atmospheric particles are directly obtained by fluorescent XAFS spectroscopy using a 19-element solid state detector (SSD). Particulate sample was collected on a quartz fiber filter using a high-volume air sampler, and the filter was cut into small pieces (25x25 mm). Then, surface layer of the filter piece was scaled and accumulated in order to enhance the particle density per filter unit. Use of 10 pieces of the surface layer enables the measurement of Pb-LIII edge XANES spectra on beamline BL01B1 at SPring-8, Hyogo, Japan. The shape of the Pb-LIII edge XANES spectra of the particulate sample is similar to the shapes of the spectra for PbS, PbCO(3), PbSO(4) and/or PbCl(2). Additionally, the filter sample is also divided into water-soluble, 0.1 M HCl-extractable, and residual fractions of Pb compounds by a simple acid extraction procedure. We discuss the possibility of Pb speciation in the particulate samples with combination of highly sensitive XANES spectroscopy and simple acid extraction.

The yield of endoscopic ultrasound-guided fine needle aspiration for histological diagnosis in patients suspected of stage I sarcoidosis.

BACKGROUND AND STUDY AIM: Sarcoidosis is a systemic disorder of unknown cause that is characterized by a pathological hallmark, noncaseating granuloma. Bilateral hilar lymphadenopathy (BHL) is a major clinical feature, but it is sometimes difficult to exclude other diseases, especially in cases where there are no pulmonary abnormalities (stage I). Bronchoscopic transbronchial biopsy is currently a popular method by which to obtain pathological material, but its diagnostic power is insignificant. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), also attempted recently, makes the sampling of pathological material easier and better, but the diagnoses are still based on cytological findings. Our study aimed to evaluate the yield of transesophageal EUS-FNA for histological confirmation of stage I sarcoidosis. METHODS: The study was a prospective comparative study to investigate the diagnostic sensitivities of FNA cytology and FNA histology. Subjects were consecutive patients with BHL without lung lesions on chest radiographs or chest CT who were referred to our hospitals between December 2003 and April 2006. Transesophageal EUS-FNA was performed with 19-gauge needles instead of the conventional 22-gauge needles. RESULTS: Forty-one patients were included in this study, and both histological and cytological materials were obtained successfully by EUS-FNA in all patients. Histopathological examination of the FNA sample showed noncaseating granuloma in 34 (94.4%) of the 36 patients with a final diagnosis of sarcoidosis. In contrast, only 28 of the 36 (77.8%) were diagnosed as having sarcoidosis on the basis of cytological findings. The difference was statistically significant (P = 0.0444). CONCLUSION: FNA histology is better suited than FNA cytology to establishing the diagnosis of stage I sarcoidosis, and EUS-FNA with a 19-gauge needle plays a important role in this process.

Baseline NIH Stroke Scale Score predicting outcome in anterior and posterior circulation strokes.

OBJECTIVE: The NIH Stroke Scale (NIHSS) may not appropriately assess the spectrum of posterior circulation (PC)-related neurologic deficits. We determined the cutoff baseline NIHSS score that predicts independent daily life activity during the chronic stage in anterior circulation (AC) vs PC ischemic strokes. METHODS: A total of 310 consecutive patients hospitalized within 3 days after the onset of an ischemic stroke were prospectively enrolled in the study. Patients on thrombolytic therapy were excluded. In all patients, infarcts and vascular lesions were identified primarily using magnetic resonance techniques. A favorable outcome was defined as a modified Rankin Scale score of < or =2 at 3 months poststroke. RESULTS: In 101 patients with PC stroke, the total baseline NIHSS score was lower (p < 0.001), and the subscores of ataxia (p < 0.001) and visual fields (p = 0.043) were higher than in 209 patients with AC stroke. Multivariate-adjusted OR for the favorable outcome in patients with PC vs AC stroke was 2.339 (95% CI 1.331-4.109, p = 0.003). A low baseline NIHSS score was independently predictive of a favorable outcome in both patients with PC (OR 1.547, 95% CI 1.232-1.941) and AC (1.279, 1.188-1.376) stroke. The optimal cutoff scores of the baseline NIHSS for the favorable outcome were < or =5 for patients with PC stroke (sensitivity, 84%; specificity, 81%) and < or =8 for patients with AC stroke (sensitivity, 80%; specificity, 82%). CONCLUSIONS: The cutoff score of the baseline NIH Stroke Scale (NIHSS) for a favorable chronic outcome was relatively low in patients with PC stroke compared to patients with AC stroke. The NIHSS appears to have limitations with respect to its use when comparing the neurologic severity of PC and AC stroke.

Endoscopic ultrasound-guided fine-needle aspiration biopsy for lymphadenopathy of unknown origin.

BACKGROUND AND STUDY AIMS: The diagnosis of mediastinal and intra-abdominal lymphadenopathy is sometimes difficult, especially in patients who have no other primary lesions. Lymphoma is one of the main causes of this condition. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe and accurate diagnostic procedure for lesions surrounding the gastrointestinal tract. However, diagnosing lymphoma using the EUS-FNA technique remains a diagnostic challenge, due to limitations in the amount of material sampled. The aim of the present study was to evaluate the yield of EUS-FNA biopsy (EUS-FNAB) using a large-gauge needle in patients with mediastinal and intra-abdominal lymphadenopathy of unknown origin, especially in relation to subclassification of the lymphomas. PATIENTS AND METHODS: Consecutive patients with mediastinal and intra-abdominal lymphadenopathy of unknown origin who were referred between October 2003 and March 2005 were enrolled in the study. EUS-FNAB was carried out using a 19-gauge needle, passing through the esophageal, gastric, and duodenal walls. Pathological diagnoses were made on the basis of histological findings, including immunopathological staining. RESULTS: A total of 104 patients were included in the study. The locations of the lymph nodes were mediastinal in 50 patients, intra-abdominal in 48 patients, and both mediastinal and intra-abdominal in six patients. The diagnoses made using EUS-FNAB were lymphoma (n = 48), metastasis (n = 16), and benign/reactive (n = 40). The overall accuracy of EUS-FNAB for unknown lymphadenopathy was 98 %, and it was possible to classify the lymphomas in accordance with the World Health Organization classifications in 88 % of cases. No serious complications occurred with the procedure. CONCLUSIONS: Open thoracic surgery, laparotomy, and other invasive diagnostic procedures such as mediastinoscopy and laparoscopy can now be avoided, as EUS-FNAB is potentially a safe and accurate tool for diagnosing unknown lymphadenopathy, including lymphoma.

Influence of sodium benzoate on the metabolism of o-xylene in the rat.

The main metabolites of o-xylene in urine are o-methylhippuric acid, o-toluic acid, o-toluic acid glucuronide, 3,4-dimethylphenol, 3,4-dimethylphenol conjugates and o-xylylmercapturic acid. The urinary excretion of o-toluic acid, o-toluic acid conjugates and o-xylene were increased by the prior administration of sodium benzoate. Conversely, the amounts of o-methylhippuric acid, 3,4-dimethylphenol conjugates and o-xylylmercapturic acid decreased by sodium benzoate pretreatment. In addition, the urinary excretion of o-methylhippuric acid was delayed by the pretreatment. The percentages of urinary excretion of the o-xylene metabolites were substantially changed by the pretreatment with sodium benzoate. These results therefore highlight a potential interaction of an air pollutant with a food additive, an interaction that remains to be established in man.

Expansion of genetically corrected neutrophils in chronic granulomatous disease mice by cotransferring a therapeutic gene and a selective amplifier gene.

Hematopoietic stem cell gene therapy has not provided clinical success in disorders such as chronic granulomatous disease (CGD), where genetically corrected cells do not show a selective advantage in vivo. To facilitate selective expansion of transduced cells, we have developed a fusion receptor system that confers drug-induced proliferation. Here, a 'selective amplifier gene (SAG)' encodes a chimeric receptor (GcRER) that generates a mitotic signal in response to estrogen. We evaluated the in vivo efficacy of SAG-mediated cell expansion in a mouse disease model of X-linked CGD (X-CGD) that is deficient in the NADPH oxidase gp91phox subunit. Bone marrow cells from X-CGD mice were transduced with a bicistronic retrovirus encoding GcRER and gp91phox, and transplanted to lethally irradiated X-CGD recipients. Estrogen was administered to a cohort of the transplants, and neutrophil superoxide production was monitored. A significant increase in oxidase-positive cells was observed in the estrogen-treated mice, and repeated estrogen administration maintained the elevation of transduced cells for 20 weeks. In addition, oxidase-positive neutrophils were increased in the X-CGD transplants given the first estrogen even at 9 months post-transplantation. These results showed that the SAG system would enhance the therapeutic effects by boosting genetically modified, functionally corrected cells in vivo.

Losartan, an angiotensin II (AT1) receptor antagonist, preserves cerebral blood flow in hypertensive patients with a history of stroke.

In patients with severe hypertension, chronic heart failure or a history of stroke, the lower limit of autoregulation of cerebral blood flow (CBF) is shifted to higher levels of blood pressure (BP) than those observed in healthy subjects. The aim of pharmacotherapy for hypertensive patients with an impaired autoregulation of CBF should be to reduce BP while preserving an appropriate CBF. In the present study, 16 hypertensive patients who had had an episode of stroke more than 4 weeks previously were administered the angiotensin II (AT1) receptor antagonist losartan at daily doses of 25-100 mg for 4 weeks. Systolic and diastolic blood pressures were recorded for 24 h using an ambulatory BP monitoring system. CBF in both hemispheres of the cerebrum and cerebellum was quantified using single photon emission tomography with N-isopropyl-p-[123I]iodoamphetamine. At baseline, CBF was 29.7 +/- 6.7 ml/min/100 g in the cerebrum and 31.5 +/- 7.5 ml/min/100 g in the cerebellum. At the end of treatment, BP was lower, while CBF increased by 7.7% in the cerebrum, and remained at the baseline level in the cerebellum. Thus, CBF was preserved despite the reduction in BP. We consider the use of losartan is advantageous for hypertensive patients with a history of stroke in whom autoregulation of CBF is potentially impaired.

Lymphoid blast crisis of chronic myelogenous leukemia occurring more than 11 years after receiving an allogeneic bone marrow transplant for chronic myelogenous leukemia in myeloid blast crisis at onset.

A 25-year-old male developed lymphoid blast crisis (BC) of chronic myelogenous leukemia (CML) more than 11 years after receiving an allogeneic bone marrow transplant (alloBMT) for CML with myeloid BC at presentation from his HLA-identical brother. The lymphoid BC of CML probably occurred without a preceding chronic phase of CML. This case illustrates the difficulties involved in determining the appropriate length of follow-up after alloBMT.

Clinical results of stenting for cervical internal carotid stenoses.

SUMMARY: Total 89 patients with cervical ICA stenosis were treated by stenting. In 74 cases of stenting, we used our blocking balloon systems to prevent distal embolism. The morbidity and the mortality rate was 4.5% and 0%, respectively.Two(3%) of 74 cases showed distal embolism when blocking balloon catheter systems(BBCS) were used, while distal embolism occurred in four (27%) of 15 cases of stenting without BBCS. On diffusion- weighted MRI (DWI), hyperintense areas were detected in seven (47%) of 15 lesions when we used BBCS only during postdilatation. On the other hand, use of BBCS during predilatation as well as postdilatation reduced hyperintense areas on DWI, which were detected in three (25%) of 12 patients. Our blocking balloon catheter system is a useful device to reduce the risk of distal embolism, especially when we use it during not only postdilatation but predilatation.

The enzymatic basis for the conversion of nonfucosylated to fucosylated alpha-fetoprotein by acyclic retinoid treatment in human hepatoma cells: activation of alpha1-6 fucosyltransferase.

The purpose of the present study was to investigate the mechanism by which nonfucosylated alpha-fetoprotein (AFP) is converted to fucosylated AFP in human hepatoma cell lines exposed to acyclic retinoid (AR), an effective drug for the secondary prevention of hepatocellular carcinoma. AR treatment (100 microM) of HepG2 and Hep3B cells significantly increased the activity and mRNA levels of alpha1-6 fucosyltransferase (alpha1-6 FucT), the enzyme responsible for the fucosylation of AFP, leading to an increase in fucosylated glycoproteins as evidenced by lectin binding measurements. Lectin immunoelectrophoresis of AFP obtained from culture media indicated that the relative percentage of nonfucosylated AFP (L1 fraction) was decreased and alpha1-6 fucosylated AFP (L3 fraction) was increased in these hepatoma cell lines after treatment with AR. The total AFP levels were, however, markedly suppressed by AR treatment, and therefore the absolute L3 fraction on the basis of the total AFP present was extremely low. These results demonstrate that AR enhances the conversion of the L1 to the L3 fraction due to the activation of alpha1-6 FucT in human hepatoma cell lines despite clinical outcome with AR treatment and the L3 fraction of AFP. Even though the dramatic decrease in AFP is the limiting factor in the synthesis of the L3 fraction and, therefore, the absolute value of fucosylated AFP is extremely low, the conversion from L1 to L3 as judged by lectin immunoelectrophoresis represents a good marker for the progress of AR treatment.

Transcortical mixed aphasia due to cerebral infarction in left inferior frontal lobe and temporo-parietal lobe.

We present a case of transcortical mixed aphasia caused by a cerebral embolism. A 77-year-old right-handed man was admitted to our hospital with speech disturbance and a right hemianopia. His spontaneous speech was remarkably reduced, and object naming, word fluency, comprehension, reading and writing were all severely disturbed. However, repetition of phonemes and sentences and reading aloud were fully preserved. Although magnetic resonance imaging (MRI) showed cerebral infarcts in the left frontal and parieto-occipital lobe which included the inferior frontal gyrus and angular gyrus, single photon emission CT revealed a wider area of low perfusion over the entire left hemisphere except for part of the left perisylvian language areas. The amytal (Wada) test, which was performed via the left internal carotid artery, revealed that the left hemisphere was dominant for language. Hence, it appears that transcortical mixed aphasia may be caused by the isolation of perisylvian speech areas, even if there is a lesion in the inferior frontal gyrus, due to disconnection from surrounding areas.