Detection of circulating tumor cells in cancers of biliary origin

Background

Circulating Tumor Cells (CTCs) have been described in malignancies of epithelial origin. In this study we examined the detection of CTCs using CellSearch assay in cholangiocarcinoma and gallbladder cancer.

Methods

The clinical outcomes and detection of CTCs were examined in sixteen patients with biliary cancer using the CellSearch assay. Stages of cancer, baseline demographic data and overall survival were evaluated.

Results

Thirteen patients had cholangiocarcinoma and three had gallbladder cancer. Using a cut off of two or more CTCs per 7.5 mL of blood, 3/13 cholangiocarcinoma and 1/3 gallbladder cancer patients had detectable CTCs. At 12 months of follow up from time CTC is drawn; 1/4(25%) of patients with positive CTC were alive while 6/12 (50%) of patients with negative CTC remained alive without a significant difference in survival between the two groups.

Conclusions

Our finding that 25% of patients with cholangiocarcinoma and gallbladder cancer have two or more detectable CTCs/7.5 mL is the first report to our knowledge in this disease. Larger patient numbers are needed to determine the prognostic significance of finding CTCs in biliary cancer. Prospective validation of the role of CTC in advanced biliary cancer patients is on going.Key Words: Biliary cancer, CellSearch, cholangiocarcinoma, circulating tumor cells, EpCAM     

Increased suicidal risk among smoking schizophrenia patients

INTRODUCTION: Schizophrenia patients display a high suicidal risk, although this risk is difficult to predict. One of the variables associated with increased suicide risk is smoking. In the present study, we assessed the suicidal risk in schizophrenia patients, smokers and nonsmokers. We also evaluated the impact of various variables such as psychotic symptoms, impulsivity, and extra-pyramidal side effects on suicidal risk. METHODS: Sixty-one schizophrenia patients responded to a battery of measures, including the suicidal risk scale (SRS), the positive and negative syndrome scale (PANSS), the impulsivity control scale, and the Simpson Angus Scale for extrapyramidal side effects. The effect of smoking on the various measures, especially suicidal risk, was examined. RESULTS: Schizophrenia patients who smoke obtained higher PANSS scores (both total score and positive and negative subscales), but did not differ on the Simpson Angus scale of extrapyramidal side effects. They also exhibited higher suicide risk as reflected by higher scores on the SRS, and a trend for higher impulsivity as measured by the impulsivity control scale. Women that smoked had higher SRS scores as compared with female nonsmokers, and also higher than in males, smokers and nonsmokers. Smoking and a history of suicide attempt predicted in our regression analysis a higher SRS score. When conducting separate analyses for the male and female patients, the significant contributors were the PANSS total score among the males and the number of pack-years among the female patients. CONCLUSIONS: Despite hints toward the role of smoking in suicidal behavior in Schizophrenia, especially among female patients, more studies are needed to elucidate the association between smoking and suicidality in schizophrenia patients.     

The intestinal microvillus. Ultrastructural variability in coeliac disease and cow's milk intolerance.

In 8 patients with coeliac disease, 2 patients with cow's milk intolerance and 10 patients with other gastrointestinal disturbances, intestinal biopsies were examined in order to compare the extent of alteration of surface vs. crypt microvilli (MV). In those diseases associated with the ingestion of a noxious agent, namely coeliac disease and cow's milk intolerance, a marked and abrupt difference between the severely damaged surface epithelium and its MV, and the preserved crypt epithelium was noted. The results of the examinations give reason to suppose that these morphological variations are caused by the higher gliadin or milk protein concentration over the avillous surface epithelium as opposed to the lower one in the elongated crypts.     

Computed tomography angiography intraluminal filling defect is predictive of internal carotid artery free-floating thrombus

Introduction

Filling defects at the internal carotid artery (ICA) origin in the work-up of stroke or transient ischemic attack may be an ulcerated plaque or free-floating thrombus (FFT). This may be challenging to distinguish, as they can appear morphologically similar. This is an important distinction as FFT can potentially embolize distally, and its management differs. We describe a series of patients with suspected FFT and evaluate its imaging appearance, clinical features, and evolution with therapy.

Methods

Between 2008 and 2013, we prospectively collected consecutive patients with proximal ICA filling defects in the axial plane surrounded by contrast on CT/MR angiography. We defined FFT as a filling defect that resolved on follow-up imaging. We assessed the cranial–caudal dimension of the filling defect and receiver operating characteristics to identify clinical and radiological variables that distinguished FFT from complex ulcerated plaque.

Results

Intraluminal filling defects were identified in 32 patients. Filling defects and resolved or decreased in 25 patients (78 %) and felt to be FFT; there was no change in 7 (22 %). Resolved defects and those that decreased in size extended more cranially than those that remained unchanged: 7.3 mm (4.2–15.9) versus 3.1 mm (2.7–3.7; p?=?0.0038). Receiver operating characteristic analysis established a threshold of 3.8 mm (filling defect length), sensitivity of 88 %, specificity of 86 %, and area under the curve of 0.86 (p?<?0.0001) for distinguishing FFT from plaque.

Conclusion

Filling defects in the proximal ICA extending cranially >3.8 mm were more likely to be FFT than complex ulcerated plaque. Further studies evaluating filling defect length as a predictor for FFT are warranted.     

Assessment of Routine Procedure Effect on Breathing Parameters in Mice by Using Whole-Body Plethysmography

We used whole-body plethysmography to investigate the effect of restraint, ear marking, tail vein and retroorbital blood sampling, and tail clipping on respiration in Balb/c × TCR-HA^+/– F1 hybrid mice (F1h). Baseline values of breathing parameters were determined. During the experiment, mice experienced a procedure and then plethysmographic recordings were obtained immediately and at 4, 24, and 48 h afterward. Baseline breathing parameters showed significant differences between sexes. Restraint affected minute volume differently than did handling in male mice and to a lesser extent in female mice. Ear marking significantly changed minute volume compared with handling but not restraint in male mice and in the opposite manner in female mice. Tail vein blood sampling changed minute volume in a significant manner compared with restraint but not compared with handling in both sexes. Retroorbital blood sampling significantly changed minute volume compared with values for both handling and restraint in male mice but only compared with handling in female mice. Tail clipping modified minute volume significantly compared with handling in male mice and compared with restraint in both sexes. Analysis of data showed that routine procedures affect minute volume in mice depending on invasiveness of maneuver and in a sex-biased manner for as long as 24 h after the procedure. Our experiment shows that procedures performed on laboratory mice can change respiratory parameters and can be investigated by plethysmography.Abbreviation: F1h, Balb/c × TCR-HA^+/– F1 hybrid miceHandling, restraint, identification methods, and blood or tissue sampling are regarded as routine procedures in animal experiments. This aspect is particularly important when working with transgenic animals, where the need for genotyping demands the frequent use of these procedures, which can readily yield DNA samples.⁵ The effect of routine procedures on physiologic parameters varies depending on method, frequency, and duration, but these procedures generally are considered to be acute stressors.^2,5,26,27 A large body of research has focused on the effect of routine procedures on animals’ physiology. These effects were assessed by studying changes in behavior,^1,23,36,37 body weight,^29,37 food and water intake,^29,37 body temperature³⁵ and heart rate by radiotelemetry,^{5,10,19,26,27} corticosterone^{11,12,24,25,29} and glucose levels,³³ and blood variables.^29,36 Several differences in the response of laboratory animals to stress have been correlated to breed,^2,33 strain,^11,14,37 age,²⁴ and sex.^12,23,24 Some authors²⁴ have noted that female mice show a lower overall stress level due to the modest effect of social competition. Another study¹² showed a different, sex-specific response to hypoxic ventilation in rats, which was higher in male than female rats. In addition, these authors¹² suggested that female ovarian hormones are prime candidates for stress regulation.Whole-body plethysmography is a noninvasive, indirect method of studying respiratory function in conscious, unrestrained animals. This method has been used particularly in pharmacologic and toxicologic studies in diverse animal species including mice,^3,9,14,15,38 rats,^8,20 cats,²² dogs,^16,34 and pigs.¹³ The present study was designed to investigate the extent to which routine procedures affect breathing parameters in a transgenic mouse colony. Male and female mice were exposed to 4 routine procedures that are used for DNA sampling and identification of transgenic mice (ear marking, tail clipping, and tail vein and retroorbital blood sampling). Respiratory parameters were recorded by whole-body plethysmography immediately and at 4, 24, and 48 h after the procedure. Handling and restraint were used as control procedures.     

Laparoscopic cholecystectomy: incidents and complications. Analysis of 8002 consecutive cholecystectomies performed at the Surgical Clinic III Cluj-Napoca

Incidents and postoperative complications of laparoscopic cholecystectomy (LC) are analyzed based on a series of 8002 patients who underwent the procedure during a period of seven years. Conversion rate was 2.02% (161 cases) and 6 (0.07%) death were encountered. Intraoperative hemorrhage (2.43%) could be controlled by intraoperative haemostasis in all but 8 patients (bleeding from the hepatic bed and from the cystic artery) which required conversion. Lesions of the bile ducts occurred in 16 patients (0.2%), 13 of them being identified during the operation and solved by conversion or laparoscopic choledochorraphy (for a tangential lesion). Postoperative complications required re-intervention in 45 patients: 11 for bile leak, 19 for choleperitoneum, 6 for hemorrhage, 4 for subhepatic abscesses and 5 for remnant CBD lithiasis. There was 1 puncture of the Douglas pouch in a case of choleperitoneum, 7 laparoscopic re-interventions and 25 open surgery re-interventions. EST solved postoperative bile leaks (from the gallbladder bed) successfully in 7 cases and remnant CBD lithiasis (5 cases). So, 44% of the cases were treated by minimally invasive means (laparoscopic re-interventions or endoscopic procedures). The majority of the incidents and postoperative complications were linked to the presence of an acute cholecystitis and were partially due to some technical limits of the laparoscopic technique of the gallbladder bed peritonisation. The minimally invasive treatment of postoperative complications, was very efficient and offered optimum healing conditions.     

Epidemiological considerations of the arbo- and arenaviruses

The complex epidemiological process of arboviral and arenaviral diseases, their dependence on a multitudine of etiologic agents, the risk of severe manifestations, absence of a specific treatment and difficulties in preparing the vaccines, place these diseases among those of high concern at national and international level. The multidisciplinary investigations carried out in Moldavia by M. Duca, Eugenia Duca, Gr. Teodorovici, Alla Va??, St. Dumitriu, V. Luca, D. Buiuc, A. Ivan and others have elucidated numerous aspects regarding the epidemiology and prevention of arboviral diseases. The increased morbidity by meningitis and meningoencephalitis recorded in Romania the interval summer--early fall 1996 was attributed based on serologic diagnosis, to West Nile virus. The etiological investigations were done both in our country (Cantacuzino Institute, Institute of Virology, Laboratory of the Ministry of National Defence) and abroad (Pasteur Institute at Paris, Colindale Institute London, CDC, Atlanta, USA). For the Romanian population the risk for a periodical re-emergence of some arbovirus diseases is due to favorable local conditions with the relationships with geographical areas were these diseases have and endemic-epidemic evolution are added.     

Design of and technical challenges involved in a framework for multicentric radiotherapy treatment planning studies

This report introduces a framework for comparing radiotherapy treatment planning in multicentric in silico clinical trials. Quality assurance, data incompatibility, transfer and storage issues, and uniform analysis of results are discussed. The solutions that are given provide a useful guide for the set-up of future multicentric planning studies or public repositories of high quality data.     

Giant ascending aortic aneurysm after aortic valve replacement

Giant ascending aortic aneurysms are rare clinical entities and are accompanied by a high annual risk of rupture. We present the imaging, intraoperative, and pathology findings of such a case.