Dental Prosthesis in Esophagus: A Right Cervicotomic Approach.

Foreign body ingestion in the upper digestive tract is a relatively common emergency. Less than 1% have to be treated surgically. We report the case of a 68-year-old man who ingested a dental prosthesis, probably during a seizure, and thus unknowingly, and presented two days later to the emergency department complaining of a mild dysphagia. A chest radiograph showed the presence of a removable dental prosthesis in the upper esophageal tract. The patient was brought to the operating room where a multidisciplinary equipe was assembled. Two attempts of retrieval with a flexible and a rigid endoscope failed because the removable dental prosthesis was stuck in the right pyriform sinus. Therefore, the surgeon performed an uncommon right cervicotomy and retrieved the foreign body through a right-side esophagotomy. The surgical approach depends on the nature and location of the foreign body. Urgent treatment is required whenever the patient develops dyspnea or dysphagia because of the high risk of inhalation and asphyxia. Removal of any esophageal foreign body has to be performed within 12-24 h. Repeated attempts to retrieve large dental prosthesis using an endoscope may result in esophageal perforation therefore when such risk of complication is too high, a surgical approach becomes inevitable. In our opinion, surgery remains the extrema ratio after a failed endoscopic retrieval attempt but can be lifesaving despite high risk of complications.

Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions: A joint statement by the European Society of Cardiology, the Council on Hypertension of the European Society of Cardiology, the European Society of Hypertension, the International Society of Mountain Medicine, the Italian Society of Hypertension and the Italian Society of Mountain Medicine.

Take home figureAdapted from Bärtsch and Gibbs2 Physiological response to hypoxia. Life-sustaining oxygen delivery, in spite of a reduction in the partial pressure of inhaled oxygen between 25% and 60% (respectively at 2500 m and 8000 m), is ensured by an increase in pulmonary ventilation, an increase in cardiac output by increasing heart rate, changes in vascular tone, as well as an increase in haemoglobin concentration. BP, blood pressure; HR, heart rate; PaCO2, partial pressure of arterial carbon dioxide.

Risk factors for postoperative recurrence of spontaneous pneumothorax treated by video-assisted thoracoscopic surgery†.

OBJECTIVES: Over the past two decades, video-assisted thoracoscopic blebectomy and pleurodesis have been used as a safe and reliable option for treatment of spontaneous pneumothorax. The aim of this study is to evaluate the long-term outcome of video-assisted thoracoscopic surgery (VATS) treatment of spontaneous pneumothorax in young patients, and to identify risk factors for postoperative recurrence. METHODS: We retrospectively analysed the outcome of VATS treatment of spontaneous pneumothorax in our institution in 150 consecutive young patients (age ≤ 40 years) in the years 1997-2010. Treatment consisted of stapling blebectomy and partial parietal pleurectomy. After excluding 16 patients lost to follow-up, in 134 cases [110 men, 24 women; mean age, 25 ± 7 standard deviation years; median follow-up, 79 months (range: 36-187 months)], we evaluated postoperative complications, focusing on pneumothorax recurrence, thoracic dysaesthesia and chronic chest pain. Risk factors for postoperative pneumothorax recurrence were analysed by logistic regression. RESULTS: Of 134 treated patients, 3 (2.2%) required early reoperation (2 for bleeding; 1 for persistent air leaks). Postoperative (90-day) mortality was nil. Ipsilateral pneumothorax recurred in 8 cases (6.0%) [median time of recurrence, 43 months (range: 1-71 months)]. At univariate analysis, the recurrence rate was significantly higher in women (4/24) than in men (4/110; P = 0.026) and in patients with >7-day postoperative air leaks (P = 0.021). Multivariate analysis confirmed that pneumothorax recurrence correlated independently with prolonged air leaks (P = 0.037) and with female gender (P = 0.045). Chronic chest wall dysaesthesia was reported by 13 patients (9.7%). In 3 patients, (2.2%) chronic thoracic pain (analogical score >4) was recorded, but only 1 patient required analgesics more than once a month. CONCLUSIONS: VATS blebectomy and parietal pleurectomy is a safe procedure for treatment of spontaneous pneumothorax in young patients, with a 6% long-term recurrence rate in our experience. Postoperative recurrence significantly correlates with female gender and with prolonged air leakage after surgery.

Farnesyltransferase inhibitors and human malignant pleural mesothelioma: a first-step comparative translational study.

It is known that the potential clinical use of farnesyltransferase inhibitors (FTI) could be expanded to include cancers harboring activated receptor tyrosine kinases. Approximately 70% of malignant pleural mesotheliomas (MPM) overexpress epidermal growth factor receptors (EGFR) and a subset express both EGFR and transforming growth factor alpha (TGF-alpha), suggesting an autocrine role for EGFR in MPM. We checked on MPM cells (10 human cell lines, 11 primary cultures obtained by human biopsies, and 7 short-term normal mesothelial cell cultures) concerning the following: (a) the relative overexpression of EGFR (Western blotting, flow cytometry, immunohistochemistry), (b) the relative expression of EGFR ligands (EGF, amphiregulin, TGF-alpha, ELISA), (c) the relative increase of the activated form of Ras (Ras-bound GTP) after EGF stimulation (Ras activation assay), (d) the efficacy of five different FTIs (HDJ2 prenylation, cell cytotoxicity, and apoptosis using ApopTag and gel ladder). EGFR was overexpressed in MPM cells compared with normal pleural mesothelial cells in equivalent levels as in non-small cell lung cancer cells A459. MPM cells constitutively expressed EGFR ligands; however, Ras activation was attenuated at high EGF concentrations (100 ng/mL). Growth of MPM cells was substantially not affected by treatment with different FTIs (SCH66336, BMS-214662, R115777, RPR-115135, and Manumycin). Among these, BMS-214662 was the only one moderately active. BMS-214662 triggered apoptosis in a small fraction of cells (not higher than 30%) that was paralleled by a slight decrease in the levels of TGF-alpha secreted by treated MPM cells. Our data highlighted the concept that the same signaling pathway can be regulated in different ways and these regulations can differ between different cells of different origin.

Tumor necrosis factor enhances SN38-mediated apoptosis in mesothelioma cells: the role of nuclear factor-kappaB pathway activation.

BACKGROUND: Despite the best and most aggressive, often integrated, standard therapeutic approaches for mesothelioma, overall survival remains very poor. The actual failure points out clearly the need for the development of novel therapy. One of the promising paths of experimentation is artificial induction of apoptosis. A therapeutic strategy that relies on the down-regulation of BCL-XL inhibition nuclear factor kappaB (NF-kappaB) with a combination of SN38 and tumor necrosis factor (TNF) was studied in human mesothelioma cell lines (MSTO-221H, IST-MES1, IST-MES2, MPP89, H28, H513, H2052, and H290). METHODS AND RESULTS: Cell proliferation (clonogenic assay) was inhibited strongly by the combination of TNF and SN38. Examining the persistence of the NF-kappaB complexes using an electrophoretic mobility-shift assay, it appeared that they still were present at 24 hours in TNF-treated cells. In SN38-treated cells, NF-kappaB complexes persisted for 6 hours. In cells that were treated with combined SN38 and TNF, NF-kappaB complexes disappeared quickly and became undetectable at 6 hours. In flow cytometry analysis, only cells that were treated with combined SN38 and TNF demonstrated significant cellular accumulation in the sub-G0-G1 phase, suggesting a specific induction of apoptosis. Morphologic examination (4,6-diamidino-2-phenylindole staining and electron microscopy) and internucleosomal DNA fragmentation (gel ladder) confirmed rigorously the induction of apoptosis. CONCLUSIONS: Because of NF-kappaB inhibition with the combination of SN38 and TNF, the expression of BCL-XL (both the protein [Western blot analysis] and the mRNA [reverse transcriptase-polymerase chain reaction analysis]) was down-regulated, cytochrome c was released into the cytoplasm, caspase 3 was activated (Western blot analysis), and, consequently, apoptosis was triggered. The authors hope that the results of the current study may contribute to the design and implementation of a novel therapeutic approach that improves patients' responses to treatment for mesothelioma.

Non-small cell lung cancer: from cytotoxic systemic chemotherapy to molecularly targeted therapy.

Surgery is the only method of cure in lung cancer. Seldom its application with radical intent is possible. Despite the efforts aimed at integrating all the therapeutic strategies, the overall outcome of the management of this disease remains disappointing. For this reason, in the last three decades, thousands of preclinical and clinical attempts have been realised in order to investigate any possible way to cure this disease and significant steps forward have been made on the basis of the increasing "molecular knowledge" in the so called "post-genomic era". Particularly the impressive step forward in the biological characterization of cancer as a result of genetic/epigenetic multistep process has brought in a multitude of variables with staggering classification potentialities. "Benchside" and "bedside" scientists have assembled in functional teams to move the common efforts "translationally" to bridge basic and clinical research for a mutual synergistic enhancement. This paper represents the effort of a lung cancer focused translational research team made up of molecular biologists, medical oncologists and thoracic surgeons to achieve a comprehensive, but simple, review of the current status of the shift from cytotoxic to molecularly targeted therapy in lung cancer treatment potentially useful in the planning of translational research trials.