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Biomedical subjects

Mohsen Ibrahim

Publications and source records attributed to Mohsen Ibrahim.

8 recordsLinked to original sources

Genetic insight into lung neuroendocrine tumors: Notch and Wnt signaling pathways as potential targets.

BACKGROUND: The molecular landscape of lung neuroendocrine neoplasms is still poorly characterized, making it difficult to develop a molecular classification and personalized therapeutic approaches. Significant clinical heterogeneity of these malignancies has been highlighted among poorly differentiated histotypes and within the subgroup of well-differentiated neuroendocrine tumors (NET). Currently, the main prognostic factors of lung NET include stage, histotype, grade, peripheral location, and demographic parameters. To gain deeper insights into the genomic underpinnings of lung NETs, we conducted a pilot investigation to uncover potential genetic mutations and copy number variations (CNVs) implicated in their pathogenesis. METHODS: Formalin-fixed, paraffin-embedded intraoperative tumor biopsies and matched peripheral blood mononuclear cell samples were collected from six consecutive patients with lung NETs. The whole exome sequencing (WES) was performed to profile germline and somatic mutations, identify novel genetic alterations, and detect CNVs. Clinical and pathological data were systematically documented at diagnosis and during follow-up. RESULTS: The WES analysis identified a subset of mutations shared between germline and somatic; some were of particular clinical interest as they were associated with tumor proliferation and potential therapeutic targets such as the genes KDM5C, ATR, COL7A1, NOTCH4, PTPRS, SMO, SPEN, SPTA1, TAF1. These mutations were predominantly linked to chromatin remodeling and were involved in critical oncogenic pathways such as Notch and Wnt signaling. CONCLUSIONS: This pilot study highlights the potential role of NGS analysis on solid biopsy in the assessment of the mutational profile of lung NET. A comparison of germline and somatic mutations is critical to identifying putative tumor driver mutations. In perspective, the enrichment of a subpopulation of cancer cells in the blood, with one or more specific mutations, is information of enormous clinical relevance, either for prognosis or therapeutic decisions. Translational studies on large prospective series are required to establish the role of liquid biopsy in lung NET.

Humans↗

Intrapleural intercostal nerve block associated with mini-thoracotomy improves pain control after major lung resection.

OBJECTIVE: To prospectively assess the impact of intrapleural intercostal nerve block (IINB) associated with mini-thoracotomy on postoperative pain and surgical outcome after major lung resections. METHODS: Between January 2004 and February 2005, we randomly assigned 120 consecutive patients undergoing mini-thoracotomy (10-13 cm) for major lung resections, to receive or not IINB from the 4th to the 8th space at the moment of thoracotomy using 20 ml (7.5 mg/ml) ropivacain injection at the dose of 4 ml for each space. Postoperative analgesia consisted of continuous intravenous infusion of tramadol (10 mg/h) and ketoralac tromethamine (3 mg/h) for 48 h for all patients. RESULTS: The two groups (60 patients each) were comparable for age, sex, pulmonary function, type and duration of the procedure. Mortality and morbidity were 0% and 10%, respectively, for the IINB group and 3.3% and 15%, respectively, for the non-IINB group (p>0.05, NS). Mean postoperative pain measured by the 'Visual Analogue Scale' were as follows: 2.3+/-1 at 1 h, 2.2+/-0.8 at 12 h, 1.8+/-0.7 at 24 h, and 1.6+/-0.6 at 48 h for the IINB group; and 3.6+/-1.4 at 1 h, 3.4+/-2 at 12 h, 2.9+/-1.2 at 24 h, and 2.0+/-1 at 48 h for the non-IINB group. Differences were significant at 1 h, 12 h, 24 h, and 48 h (p<0.05). Mean postoperative hospital stay was 5.7 days in the IINB group and 6.5 days in the non-IINB group (p<0.05). CONCLUSION: IINB associated with mini-thoracotomy reduces postoperative pain and contributes to improve postoperative outcome after major pulmonary resections.

Aged↗

Glutaraldehyde preserved autologous pericardium for patch reconstruction of the pulmonary artery and superior vena cava.

We describe a new employment of glutaraldehyde preserved autologous pericardium for patch reconstruction of the pulmonary artery (PA) and superior vena cava (SVC). This technique was devised to minimize technical problems related to the use of fresh pericardium such as excessive elasticity and tendency to curl. We have successfully employed this procedure in three cases of reconstruction of the PA and in two cases of reconstruction of the SVC.

Fixatives↗

Operative and non-operative treatment of benign subglottic laryngotracheal stenosis.

OBJECTIVE: Surgery is the first line of treatment for laryngotracheal stenosis; Montgomery tube or permanent tracheostomy have been so far the only alternatives. Nd-YAG laser resection and indwelling endotracheal stents have rarely been used in subglottic stenosis for anatomic and technical reasons. We have used the latter approach to optimize the timing of surgery or to achieve palliation without tracheostomy. METHODS: Between 1991 and 2001 we have treated 18 patients with subglottic stenosis (10 males, 8 females; age range 14-78, mean 34). The upper margin of the stricture was 2mm to 1cm below the vocal cords; the stenotic segment extended from 1.5 to 5 cm. Three patients had tracheostomy done elsewhere. Four patients (Group I) had laser and stenting by a Dumon prosthesis as the only treatment; six had laser and stenting (#4) followed after 1-6 months by laryngotracheal resection (Group II); eight had surgery alone (Group III). RESULTS: In Group I, one patient required repositioning of the stent and in two the stent was removed; two patients died of their underlying disease; at a follow-up of 2-9 years all living patients did well but required permanent aerosolized therapy and periodical bronchoscopy. In Group II, we had two wound infections due to airway colonization by staphylococcus aureus. In Group III, two patients developed anastomotic postoperative stenosis, treated by laser (#2) and stenting (#1), and one patient with previous tracheostomy had a wound infection. Overall, in the 14 surgical patients (Groups II and III) stenosis occurred in 14.2% and infection in 21.3%. After a follow up of 15 months to 12 years, all surgical patients breathe and speak well. CONCLUSIONS: Laser resection and endoluminal stenting can be a viable alternative to surgery or optimize the timing of operation in patients with subglottic stenosis.

Adolescent↗

Sleeve resection after induction therapy.

Preoperative chemoradiotherapy seems to improve the overall survival in locally advanced lung cancer but may also expose patients to an increased risk of postoperative complications. In particular, extended procedures, such as pneumonectomy, and especially right pneumonectomy, are associated with increased morbidity and mortality. Therefore, the extent of the procedure should be carefully weighed against the oncologic completeness of the resection. Among the potential sources of complications, special concern is given to bronchial healing, because of the impairment in bronchial blood flow caused by chemotherapy and radiation therapy. Accordingly, bronchial sleeve lobectomy after induction therapy was not widely accepted as an alternative to pneumonectomy, until the current authors showed that even complex bronchial and vascular procedures can be done safely and effectively in this setting. Many controversial issues still exist, and this article provides an updated summary of the different views and experiences.

Antineoplastic Combined Chemotherapy Protocols↗

Biopsy of anterior mediastinal masses under local anesthesia.

Treatment of most primary mediastinal tumors is based on positive histological diagnosis; we describe a variation of anterior mediastinoscopy under local anesthesia. After infiltration with local anesthetic, a transverse skin incision is made in the second, third, or fourth interspace. The endothoracic fascia is incised vertically adjacent to the periosteum and a mediastinoscope is inserted in the mediastinum. Between 1995 and 2001, we have employed this technique in 46 patients with anterior mediastinal tumors. Histological diagnosis was obtained in all patients. Pneumothorax (2 patients) was drained by a tube removed at the end of the procedures. No other complications occurred and all patients were discharged from hospital within 24 hours. Mediastinoscopy under local anesthesia proved safe and effective for diagnosing anterior mediastinal tumors.

Adolescent↗