Superior mediastinal and neck lymphatic mapping in mid- and lower-thoracic esophageal cancer as defined by ferumoxides-enhanced magnetic resonance imaging

Objective: The purpose of this study was to detect lymphatic drainage into the superior mediastinum and neck in thoracic esophageal cancer patients using ferumoxides-enhanced magnetic resonance imaging (MRI), and to have this information assist in determining the appropriate extent of lymphadenectomy. Methods: Nine male patients with T2–T3 mid- and lower-thoracic esophageal cancer with lymph node metastasis were examined. The day before surgery, ferumoxides was endoscopically injected into the submucosal layer of the peritumoral lesion. Thereafter, lymph nodes in the superior mediastinum and neck, which were shown to be ferumoxides-enhanced on MRI, were harvested and evaluated; magnetic force from all harvested lymph nodes was measured ex vivo. Results: MRI of the superior mediastinum and neck revealed l(median) ferumoxides-enhanced lymph nodes in eight (89%) patients, and there was laterality in the lymphatic mapping in both areas. Of the 15 lymph nodes into which drainage was detected by enhanced MRI, 12 (80%) were magnetite-positive. In six patients (67%), magnetic resonance enhanced lymph nodes corresponded completely with the ex vivo magnetite examination, and in 3 patients (33%) there was partial agreement In 3 (60%) of the 5 patients that showed paratracheal and/or supraclavicular lymph node metastases, all of the affected nodes were detected by MRI; in one patient some of the affected nodes were detected. Conclusion: Ferumoxides-enhanced MRI is useful for visualizing lymphatic drainage to the superior mediastinum and neck in thoracic esophageal cancer. It is an adequate procedure to form an estimate on the appropriate extent of lymphadenectomy. Read at the Fifty-sixth Annual Meeting of the Japanese Association for Thoracic Surgery, Symposium, Tokyo, November 19–21, 2003.     

Immuolocalization of nestin in pancreatic tissue of mice at different ages

AIM： To localize nestin positive cells （NPC） in pancreatic tissue of mice of different ages. METHODS： Paraffin sections of 6-8 um of fixed pancreatic samples were mounted on poly-L-lysine coated slides and used for Immunolocalization using appropriate primary antibodies （Nestin, Insulin, Glucagon）, followed by addition of a fluorescently labeled secondary antibody. The antigen-antibody localization was captured using a confocal microscope （Leica SP 5 series）. RESULTS： In 3-6 d pups, the NPC were localized towards the periphery of the endocrine portion, as evident from immunolocalization of insulin and glucagon, while NPC were absent in the acinar portion. At 2 wk, NPC were localized in both the exocrine and endocrine portions. Interestingly, in 4-wk-old mice NPC were seen only in the endocrine portion, towards the periphery, and were colocalised with the glucagon positive cells. In the pancreas of 8- wk-old mice, the NPC were predominantly localized in the central region of the islet clusters, where immunostaining for insulin was at a maximum. CONCLUSION： We report for the first time the immunolocalization of NPC in the pancreas of mice of different ages （3 d to 8 wk） with reference to insulin and glucagon positive cells. The heterogeneous localization of the NPC observed may be of functional and developmental significance and suggest（s） that mice pancreatic tissue can be a potential source of progenitor cells. NPC from the pancreas can be isolated, proliferated and programmed to differentiate into insulin secreting cells under the appropriate microenvironment.     

Target identification of drug induced mitochondrial toxicity using immunocapture based OXPHOS activity assays.

Mitochondrial dysfunction has been shown to be a pharmacotoxicological response to a variety of currently-marketed drugs. In order to reduce attrition due to mitochondrial toxicity, high throughput-applicable screens are needed for early stage drug discovery. We describe, here, a set of immunocapture based assays to identify compounds that directly inhibit four of the oxidative phosphorylation (OXPHOS) complexes: I, II, IV, and V. Intra- and inter-assay variation were determined and specificity tested by using classical mitochondrial inhibitors. Twenty drugs, some with known mitochondrial toxicity and others with no known mitochondrial liability, were studied. Direct inhibition of one or more of the OXPHOS complexes was identified for many of the drugs. Novel information was obtained for several drugs including ones with previously unknown effects on oxidative phosphorylation. A major advantage of the immunocapture approach is that it can be used throughout drug screening from early compound evaluation to clinical trials.     

Is carotid angioplasty and stenting more cost effective than carotid endarterectomy?

OBJECTIVE: Carotid angioplasty and stenting (CAS) has been advocated as a minimally invasive and inexpensive alternative to carotid endarterectomy (CEA). However, a precise comparative analysis of the immediate and long-term costs associated with these two procedures has not been performed. To accomplish this, a Markov decision analysis model was created to evaluate the relative cost effectiveness of these two interventions. METHODS: Procedural morbidity/mortality rate for CEA and costs (not charges) were derived from a retrospective review of consecutive patients treated at New York Presbyterian Hospital/Cornell (n = 447). Data for CAS were obtained from the literature. We incorporated into this model both the immediate procedural costs and the long-term cost of morbidities, such as stroke (major stroke in the first year = $52,019; in subsequent years = $27,336/y; minor stroke = $9419). We determined long-term survival rate in quality-adjusted life years and lifetime costs for a hypothetic cohort of 70-year-old patients undergoing either CEA or CAS. Our measure of outcome was the cost-effectiveness ratio. RESULTS: The immediate procedural costs of CEA and CAS were $7871 and $10,133 respectively. We assumed major plus minor stroke rates for CEA and CAS of 0.9% and 5%, respectively. We assumed a 30-day mortality rate of 0% for CEA and 1.2% for CAS. In our base case analysis, CEA was cost saving (lifetime savings = $7017/patient; increase in quality-adjusted life years saved = 0.16). Sensitivity analysis revealed major stroke and death rates as the major contributors to this differential in cost effectiveness. Procedural costs were less important, and minor stroke rates were least important. CAS became cost effective only if its major stroke and mortality rates were made equivalent to those of CEA. CONCLUSION: CEA is cost saving compared with CAS. This is related to the higher rate of stroke with CAS and the high cost of stents and protection devices. To be economically competitive, the mortality and major stroke rates of CAS must be at least equivalent if not less than those of CEA.     

Unusual and rare manifestations of dengue during a dengue outbreak in a tertiary care hospital in South India

Dengue is the most rapidly spreading mosquito-borne viral disease in the world, and as a larger proportion of the population is being affected, more unusual manifestations are being reported. Very few studies have documented unusual manifestations of dengue in South India. This prospective study was undertaken from July 2011 to June 2013 to document rare manifestations of dengue fever in 175 hospitalized patients. The clinical diagnosis was confirmed by the detection of NS1Ag, dengue IgM, or IgG by ELISA and/or a RT-PCR and CDC real-time PCR for dengue virus (DENV) RNA. The daily profiles of the hematological and biochemical investigations were followed and recorded. Unusual and rare manifestations of dengue were documented for 115 patients (66 %). Hepatitis was observed in 70 % of the cases. Pleural effusion was seen in 11 %, acute renal failure in 10 %, neurological complications such as encephalitis in 7.4 %, myocarditis in 9 %, and bleeding gastric ulcers in 3.4 % of the cases. DENV serotype 2 was more prevalent in patients with unusual manifestations of dengue in our study. The WHO classification system does not include unusual and rare manifestations; hence, it is essential to be aware of these manifestations and closely monitor them for better clinical management and outcome of patients.     

Initial experience with the EndoAssist camera-holding robot in laparoscopic urological surgery

Although the advantages of laparoscopic surgery are well documented, one disadvantage is that, for optimum performance, an experienced camera driver is required who can provide the necessary views for the operating surgeon. In this paper we describe our experience with urological laparoscopic techniques using the novel EndoAssist robotic camera holder and review the current status of alternative devices. A total of 51 urological procedures (25 using the EndoAssist device and 26 using a conventional human camera driver) conducted by three experienced surgeons were studied prospectively, including nephrectomy (simple and radical), pyeloplasty, radical prostatectomy, and radical cystoprostatectomy. The surgeon noted the extent of body comfort and muscle fatigue in each case. Other aspects documented were ease of scope movement, i.e. usability, need to clean the telescope, time of set-up, surgical performance, and whether it was necessary to change the position of the arm during the surgery. All three surgeons involved in the evaluation felt comfortable throughout all procedures, with no loss of autonomy. It was, however, obvious that the large arc generated whilst doing a nephrectomy led to more episodes of lens cleaning, and the arm had to be relocated on some occasions. Clearer benefits were seen while performing pelvic surgery or pyeloplasty, perhaps because the arc of movement was smaller. The EndoAssist is an effective, easy to use device for robotic camera driving which reduces the constraint of having to have an experienced camera driver for optimum visualisation during laparoscopic urological procedures.