Prediction of nodal metastasis by comparative genomic hybridization in biopsy specimens from patients with superficial esophageal squamous cell carcinoma.

PURPOSE: Selection of appropriate protocols for treatment of superficial esophageal squamous cell carcinoma (SESCC) is dependent on lymph node metastasis status. Therefore, it is important to know whether lymph node metastasis is present before treatment. EXPERIMENTAL DESIGN: In this study, we examined the relation between DNA sequence copy number aberrations detected by comparative genomic hybridization and lymph node metastasis in 26 surgically resected SESCCs (training samples). We then assessed whether the genetic information is predictive for nodal status in biopsy specimens from eight newly enrolled patients with SESCC (blinded samples). RESULTS: Pathological examination revealed that 17 of 26 training samples (65.4%) did not have associated lymph node metastasis. Gains of 8q24 and/or 20q12-qter were observed in 12, including all (nine of nine) with nodal metastasis. Fourteen training samples did not have gain of either 8q24 or 20q12-qter. Of the blinded samples, two showed no gain of 8q24 or 20q12-qter, and as anticipated the postoperative pathological examination revealed no nodal metastasis. The remaining six blinded samples had gains of 8q24 and/or 20q12-qter, and lymph node metastasis was detected by postoperative examination in four of these tumors. CONCLUSIONS: Absence of gains of 8q24 and/or 20q12-qter appears to be associated with absence of lymph node metastasis in patients with SESCC; therefore, less invasive surgery can be chosen.     

Endoscopically proven case of rapid esophagogastric variceal progression and rupture as a result of portal hypertension with liver sarcoidosis

Sarcoidosis is a multi‐systemic disease of unknown etiology that results in the development of non‐caseating epithelioid granulomas. The liver is the third most frequently involved organ after the lymph nodes and the lungs. Most cases of liver sarcoidosis do not present with symptoms and involve minimal liver dysfunction, but some cases display progression to portal hypertension and liver cirrhosis, and finally to liver failure. The mechanism and the risk of progression in liver sarcoidosis are still unknown because of the diagnostic difficulty associated with this condition, and because follow‐up examinations can only be done in an invasive manner. Here, we present an informative case of liver sarcoidosis with rapid progression of esophagogastric varices. Four months prior to the definitive diagnosis, no signs of varices were observed on endoscopy, and developmentof esophagogastric varices, rapid progression, and eventual rupture occurred in a short period of time. A liver biopsy, carried out after endoscopic sclerotherapy, revealed that granulomas primarily affected the portal area without fibrotic and cirrhotic changes, which is considered a primary cause of portal hypertension and esophagogastric varices. Following the liver biopsy, the patient was given systemic steroids and is currently receiving outpatient care. Thus, we should consider the possibility that liver sarcoidosis, even in the absence of cirrhotic changes, can cause serious events such as esophagogastric variceal rupture following rapid progression as a result of portal hypertension.     

An Exploratory Study of Dapagliflozin for the Attenuation of Albuminuria in Patients with Heart Failure and Type 2 Diabetes Mellitus (DAPPER)

Background and Aims

Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, which are anti-diabetic drugs, reportedly decrease the incidence of cardiovascular events in high-risk patients with cardiovascular diseases, and thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of not only chronic kidney disease but also cardiovascular events, we hypothesized that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of albuminuria and also improve CHF concomitantly.

Methods

DAPPER (UMIN000025102) is a multicenter, randomized, open-labeled, parallel-group, standard treatment-controlled study, which is designed to evaluate whether dapagliflozin, one of the SGLT-2 inhibitors, decreases albuminuria in T2D patients with CHF and exerts cardioprotective effects on the failing heart. The patients are randomized to either of the dapagliflozin (5 or 10 mg, once daily orally) or control group (administration of anti-diabetic drugs administered other than SGLT 2 inhibitors). The estimated number of patients that need to be enrolled is 446 in total (223 in each group). The primary objective is the changes in the urinary albumin-to-creatinine ratio from the baseline after 2-year treatment. The key secondary objectives are (1) the safety of dapagliflozin and (2) the cardiovascular and renal efficacies of dapagliflozin.

Conclusion and Perspectives

DAPPER study investigates whether dapagliflozin decreases albuminuria and exerts beneficial effects on the failing heart in T2D patients. (UMIN000025102).

     

A case of small cell lung carcinoma complicated by Lambert-Eaton myasthenic syndrome]

A 54-year old man was admitted with general fatigue, muscle weakness and dyspnea on effort. Medical examinations led to a diagnosis of small cell lung carcinoma (SCLC) with Lambert-Eaton myasthenic syndrome (LEMS). Marked improvement of SCLC and symptoms of LEMS were recognized twice during chemoradiotherapy. On his third admission, he showed muscle weakness, dysaethesia, and neurodysfunction of the bladder and rectum. We initially considered these symptoms to be due to spinal metastasis because MRI findings showed multiple spinal metastases. However, electoromyogram and nerve conduction study demonstrated that his muscle weakness resulted from LEMS though dysethesia and neurodysfunction of bladder and rectum were caused by spinal metastasis. We believe that it is important to perform electomyogram and nerve conduction studies, not only radiographic findings, to detect the "hidden" symptoms of LEMS.     

Pyrimethamine-sulfadoxine treatment of uncomplicated Plasmodium falciparum malaria in Lao PDR

A 28-day in vivo treatment trial to evaluate the efficacy of pyrimethamine/sulfadoxine (Fansidar, PS) was conducted in 21 Lao patients with uncomplicated Plasmodium falciparum malaria. Sixteen patients (76%) were completely cured with PS without any reappearance of asexual stage parasitemia during the follow-up examination. On the other hand, 5 patients (24%) failed to respond to this trial medication, resulting in recrudescence of asexual stage P. falciparum malaria. PS resistance resulted in higher prevalence of post-treatment gametocytemia, 25% gametocyte carriers among PS sensitive cases versus 75% of the resistant cases. These findings suggest that although the level of PS resistance is still valid for treatment of malaria in the study area of Lao PDR, post-treatment induction of gametocytemia among resistant cases may result an increase in transmission rate of PS resistant falciparum malaria.     

Isolation of measles virus from middle ear fluid of infants with acute otitis media

Measles virus was isolated from the middle ear fluid (MEF) of two infant cases of acute otitis media (AOM) associated with measles. This is the first report on the isolation of measles virus from the MEF in patients with AOM, and possibility of the measles virus as a causative agent of AOM was suggested.     

The clinical value of assessing right ventricular diastolic function after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) has a poor prognosis because of the associated progressive right heart failure. Accurate evaluation of right ventricular (RV) function would thus be useful to predict prognosis. However, the significance of RV diastolic function remains unclear. We aimed to identify which echocardiographic measures are most accurate, and potentially useful, in assessing RV diastolic function in patients with CTEPH, and to study the effects of balloon pulmonary angioplasty (BPA) on them. We enrolled 53 CTEPH patients who underwent BPA. Echocardiographic parameters, including two-dimensional speckle-tracking echocardiography, were compared to the hemodynamic parameters measured by right heart catheterization before and after BPA. RV strain rate during early diastole (SR_E), tricuspid e′ and right atrial area (RAA) were ameliorated after BPA, concomitant with a decrease in the time constant of the RV pressure curve during diastole (tau), indicating the improvement of RV diastolic function. Among them, SR_E had the strongest correlation with tau (r?=???0.39, p?<?0.001). Furthermore, the receiver operating characteristic analyses revealed that E/SR_E (AUC 0.704) and inferior vena cava diameter (AUC 0.726) had a stronger association with higher mean right atrial pressure than RAA (AUC 0.632). In contrast, RAA had a stronger correlation with 6 min-walk distances than SR_E (r?=???0.39, p?<?0.001 vs. r?=?0.30, p?=?0.005). Taken together, echocardiographic assessment of RV diastolic function might be associated with hemodynamics as well as exercise tolerance in patients with CTEPH, indicating its benefits in evaluating the therapeutic effects of BPA.     

Alpha-fetoprotein-producing gastric carcinoma: Biological properties of a cultured cell line

We describe a gastric carcinoma cell line that has been maintained in vitro for more than 10 years and retains the capacity to produce a large amount of alpha-fetoprotein. This cell line was isolated from a metastatic lymph node of a 63-year-old male patient with advanced gastric carcinoma (T2N3P0H0M0) who showed high serum levels of alpha-fetoprotein. The primary tumor was moderately differentiated tubular adenocarcinoma and the lymph node was poorly differentiated adenocarcinoma without any particular pattern. The cultured cells grew as densely packed islet-like colonies with small polygonal cells. Electron microscopy revealed cells abundant in cytoplasmic organelles, with some cellular attachments being tight with junctional complexes and some being loose across intercellular spaces. The free cell surface had microvilli. The population doubling-time was 152 h at passage 58. Chromosomal analysis revealed the modal number to be 77, with numerous karyotype abnormalities. The tumorigenicity of the cultured cells in athymic nude mice was positive only when they were subcutaneously transplanted beneath a plastic plate, but when the cells were transplanted subcutaneously or administered by intrasplenic injection in intact or weakly irradiated nude mice, no tumorigenicty was shown. The cell line produced tumor-associated antigens, such as alpha-fetoprotein, carcinoembryonic antigen, and tissue polypeptide antigen. This cell line may be useful for comparative studies of different types of gastric carcinoma and alpha-fetoproteins of different origins.