Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

Glucocorticoid effects on axonal regeneration of retinal ganglion cells in vitro

Although glucocorticoids are commonly used for the treatment of optic nerve inflammations, little is known about direct effects of steroids on retinal nerve cells. In this study, the neuritogenic effect of prednisolone on retinal ganglion cells was investigated using retinal organ cultures derived from adult rats and embryonic chickens. The numbers of axons growing from retinal ganglion cells (RGC) in vitro were counted to measure the regenerative propensity at various corticosteroid concentrations. Prednisolone exerted a dose-dependent neuritogenic influence on RGC of either origin. The effect was highest at a concentration of 25 μg/ml culture medium, where axon numbers increased to 237% (rat) and 166% (chick) of the control values. This was highly significant (t-test: P < 0.01 and P < 0.005, respectively). High corticosteroid concentrations (>125 μg/ml) produced toxic effects, as revealed by low axon numbers as well as morphological alterations of the explants.     

Insulin-like growth factor-I promotes nerve regeneration through a nerve graft in an experimental model of facial paralysis

Among the pathological sequelae of facial paralysis is a paralytic eye. Apart from the psychological and aesthetic deficits, facial paralysis if left untreated can lead to dryness, ulceration and eventual blindness. Although numerous restorative microsurgical approaches have been introduced to address the sequelae of this problem, complete restoration of function to denervated facial muscles remains elusive.Utilizing the rat model of facial paralysis the present research has as an objective to examine a dual treatment approach. Specifically, this study combined the current microsurgical treatment of the cross-facial nerve graft with local administration of insulin-like growth factor I (IGF-I).The efficacy of this combined approach (cross-facial nerve graft + IGF-I) was assessed in the following ways: (a) behavior measurement of the blink response and (b) histomorphometry light and electron microscopy of the entire nerve graft. These data will help provide insight into the restoration of facial muscle function after trauma and assist in the future development of more potent treatment strategies.7he local adnünistration of IGF-I (50 micro g/ml) to the cross-facial nerve graft was found to restore the blink response faster and to strengthen the degree of eye closure. Light microscopy examination revealed that IGF-I significantly enhanced axonal regeneration within a nerve graft (a 22% increase in the mean number of axons), and increased the mean nerve fiber diameter and myelin thickness. Electron microscopy assessment of the nerve grafts demonstrated that the IGF-I treated grafts possessed a greater density of microtubules, which were evenly distributed within the axoplasm.     

Adult Retinofugal Axons Regenerating Through Peripheral Nerve Grafts Can Restore the Light-induced Pupilloconstriction Reflex

To investigate the ability of mature regenerating retinal axons to form functional connections within central targets, severed axons were guided into the primary visual centres which subserve the pupillary constriction reflex in response to light. The ocular stump of the transected optic nerve of adult rats was connected by means of an autologous peripheral nerve graft with the pretectal region which contains the relay nucleus of pupillary constriction, the olivary pretectal nucleus. This nucleus is efferently connected with preganglionic neurons in the oculomotor nuclear complex which innervates parasympathetically the muscle constrictors of the iris. Six to sixteen weeks after optic nerve transection and peripheral nerve transplantation, brisk responses were observed in the pupils upon illumination of the transplanted eye. Recovery of the pupil responses indicated that retinal neurons used the peripheral nerve 'bridge' to access the pretectum, in which they established synaptic contacts in sufficient density and with appropriate specificity to reconstitute the function of the traumatically interrupted neuronal circuitry.     

Obesity Surgery Poly-parametric Patient Auto-evaluation

A simple auto-evaluation sheet is presented for the proper assessment of the patient's condition after surgery. Stress is put not only on weight loss, but on other important factors as well.     

Colorectal endoscopic submucosal dissection: Systematic review of mid‐term clinical outcomes

With a drive towards minimally invasive surgery, endoscopic submucosal dissection (ESD) is now gaining popularity. In a number of East Asian countries, ESD is now the treatment of choice for early non‐metastatic gastric cancer, but the outcomes of ESD for colorectal lesions are unclear. The present review summarizes the mid‐term outcomes of colorectal ESD including complication and recurrence rates. A systematic literature search was done in May 2014, identifying 20 publications reporting the outcomes of colorectal ESD which were included in this review. En‐bloc resection rates, complete (R0) resection rates, endoscopic clearance rates, complication and recurrences rates were analyzed. Statistical pooling was done to calculate weighted means using random effects modeling. Twenty studies reporting the outcomes of 3060 colorectal ESD procedures were reported. Overall weighted en‐bloc resection rate was 89% (95% CI: 83–94%), R0 resection rate 76% (95% CI: 69–83%), endoscopic clearance rate 94% (95% CI: 90–97%) and recurrence rate 1% (95% CI: 0.5–2%). Studies that followed up patients for over 1 year were found to have an en‐bloc resection rate of 91% (95% CI: 86–96%), R0 resection rate of 81% (95% CI: 75–88%), endoscopic clearance rate 93% (95% CI: 90–97%) and recurrence rate of 0.8% (95% CI: 0.4–1%). Colorectal ESD can be carried out effectively and safely with a 1% recurrence rate. Further studies with longer follow‐up periods are required to determine whether colorectal ESD is a viable alternative to conventional surgical therapy.     

Re-do aortic valve replacement: does a previous homograft influence the operative outcome?

BACKGROUND AND AIM OF THE STUDY: Late reoperation for failed aortic homograft is widely regarded as a high-risk procedure. A review is presented of the authors' experience of redo-aortic valve replacement (re-do AVR) examining factors which affect, and whether a previous aortic homograft replacement influences, operative outcome. METHODS: A retrospective review was conducted of consecutive re-do AVR performed at the authors' institution between 1998 and 2002. RESULTS: During the study period, 178 patients (125 males, 53 females; mean age 52.4 years; range: 16-85 years) underwent re-do AVR. The group included first-time (72%), second-time (20%), and more than third-time re-do AVR (8%). Forty-six patients (26%) received a homograft (group I), and 132 (74%) a stented biological/mechanical valve (group II). The two groups were matched for baseline clinical characteristics and operative variables. The type of explanted valve, and preoperative and operative variables, were analyzed using univariate and multivariate models. Primary outcome was defined as 30-day mortality, and secondary outcome as postoperative complications. The overall 30-day mortality was 12.3%, but was much lower (4.5%) for elective isolated and multiple re-do AVR. Univariate analysis showed significant predictors of 30-day mortality to be: age >65 years (p = 0.02); renal dysfunction (p = 0.005); preoperative unstable status (p = 0.03); preoperative NYHA class III/IV dyspnea (p = 0.02); non-elective operation (p = 0.01); preoperative arrhythmia (p = 0.005); history of chronic obstructive pulmonary disease (COPD) (p = 0.002); preoperative cardiogenic shock (p = 0.03); impaired left ventricular ejection fraction (LVEF) <50% (p = 0.04); and other valvular procedure(s) performed simultaneously (p = 0.01). In a multivariate analysis, the only significant predictors of 30-day mortality were impaired LVEF (p = 0.03) and a history of COPD (p = 0.007). Group I patients had a significantly shorter mean hospital stay (10.2+/-5.9 versus 14.1+/-12.5 days; p = 0.009), but there were no significant differences between groups in terms of postoperative complications. CONCLUSION: A previous aortic homograft replacement was not associated with an increased operative risk at the time of re-do AVR. A history was COPD was an important predictor of 30-day mortality, and this finding requires further investigation.     

Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia

Seventy-five patients, 13 to 49 years of age, with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, fractionated total body irradiation, and marrow transplantation from an HLA-identical sibling and randomized to receive either cyclosporine (CSP) (n = 36) or methotrexate (MTX) (n = 39) as prophylaxis for graft-v-host disease (GVHD). All patients engrafted, and 22 who were given CSP and 21 who were given MTX, are alive at 20 to 47 (median, 35) months (P = .5). Engraftment as assessed by granulocyte recovery (P less than .0005) and platelet transfusion requirement (P = .01) was faster in patients on CSP. Twelve patients (33%) on CSP and 22 (56%) on MTX developed acute GVHD of grades II through IV (P = .07) and 15 of 30 on CSP and 14 of 32 on MTX that were at risk developed chronic GVHD. The most frequent causes of death were interstitial pneumonitis and marrow relapse of leukemia, which occurred with similar frequency in both groups. Beneficial effects observed in patients on CSP included less severe mucositis and shorter duration of hospitalization; adverse effects included renal function impairment and hypertension. These data confirm that CSP is a useful immunosuppressant in patients undergoing marrow transplantation but fail to show a significant improvement in survival as compared with the standard regimen of MTX.