Siyamek Neragi-Miandoab

Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors.

AbstractBackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive tumor for which no effective therapy exists despite the discovery of many possible molecular and genetic targets. The late stage of MPM diagnosis and the long latency that exist between some exposures and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects.MethodsThis manuscript is a review of current literature about the pathogenesis of malignant mesothelioma. In this overview, current published studies concerning pathogenesis of malignant mesothelioma are reviewed, with insights into its etiology and pathogenesis. We searched pubmed using the following subjects: mesothelioma, radiation, genetics, pediatric malignant mesothelioma, SV40 virus, and growth factors. We selected 350 valuable articles of which 152 sources were used to complete this review.ConclusionMany risk factors for MPM development have been recognized including environmental exposures, genetic susceptibility, viral contamination, and radiation. In this review, we discuss the current molecular and genetic contributors to MPM pathogenesis and the risk factors associated with these carcinogenic processes.

Central pancreatectomy without anastomosis

BackgroundCentral pancreatectomy has a unique application for lesions in the neck of the pancreas. It preserves the distal pancreas and its endocrine functions. It also preserves the spleen.MethodsThis is a retrospective review of 10 patients who underwent central pancreatectomy without pancreatico-enteric anastomosis between October 2005 and May 2009. The surgical indications, operative outcomes, and pathologic findings were analyzed.ResultsAll 10 lesions were in the neck of the pancreas and included: 2 branch intraductal papillary mucinous neoplasms (IPMNs), a mucinous cyst, a lymphoid cyst, 5 neuroendocrine tumors, and a clear cell adenoma.ConclusionCentral pancreatectomy without pancreatico-enteric anastomosis for lesions in the neck and proximal pancreas is a safe and effective procedure. Morbidity is low because there is no anastomosis. Long term endocrine and exocrine function has been maintained.

Preoperative evaluation and a risk assessment in patients undergoing abdominal surgery

Patients who undergo abdominal surgery present along a variable spectrum of health. This ranges from the healthy young patient undergoing elective hemorrhoid surgery to the octogenarian in unstable health with multiple comorbidities. Regardless of a patient’s current state of health, a preoperative assessment is crucial in planning the operative approach and in recognizing the possible postoperative complications for the implementation of a proper intervention if necessary. A broad evaluation of the patient includes identifying conditions that may predispose the patient to risks and the complications not directly related to the surgical procedure. The purpose of this article is to review the preoperative assessment in patients undergoing simple to complex procedures. The article provides general guidelines for the preoperative workup, which should be individualized for each patient, and the planned procedure, with the goal of reducing the postoperative complications. Risk stratification depends on a patient’s condition and the extension of the planned surgical approach. It may also help to improve the postoperative outcome. A further preoperative workup should be individualized and tailored to the complexity of each case.

Surgical and other invasive approaches to recurrent pleural effusion with malignant etiology

With an increasing number of cancer survivors, the annual incidence of malignant pleural effusions has been rising in recent decades worldwide. Many patients with various forms of cancer develop malignant pleural effusions at some point in their life. Patients most commonly present with progressive dyspnea. These effusions are refractory and are associated with impaired quality of life for these patients. The main goals of management are evacuation of the pleural fluid and prevention of its re-accumulation. The therapy plan should consider the general health of the patients, their performance status, the presence of trapped lung, and the primary malignancy. However, there is no universally established, standard approach. Surgical options include thoracentesis, chest tube drainage, thoracoscopy followed by chemical and mechanical pleurodesis, Pleur-X catheter drainage, and pleurectomy. Chemical pleurodesis is the most common modality of therapy for patients with recurrent pleural effusion. For example, Talc is the most successful pleurodesis agent with similar equal to that of poudrage or slurry. Pleur-X catheter can reduce hospital stay and adds value to the treatment of patients with trapped lung, who are not appropriate candidates for pleurodesis. Furthermore, a mechanical pleurodesis has been shown to be effective particularly in pleural effusions with lower pH. This article reviews the surgical and other invasive options as well as their technical aspects in the management of recurrent malignant pleural effusions.

Incidence of atrial fibrillation after extrapleural pneumonectomy vs. pleurectomy in patients with malignant pleural mesothelioma

Extrapleural pneumonectomy (EPP) and pleurectomy are the surgical procedures for the treatment of pleural mesothelioma. However, EPP increases the risk for postoperative atrial fibrillation (AF). We conducted a retrospective chart review of 130 patients who underwent EPP or pleurectomy. Seventy patients (excluding three patients with a prior history of AF) underwent EPP and 57 patients underwent pleurectomy. The mean ages were 60+/-11 and 63+/-13 years, and the male to female ratios were 50/20 and 44/13, respectively. Postoperative AF was observed in 45 patients with 36 (51%) of these cases occurring after EPP and 9 (17%) after pleurectomy (P<0.0001). There were no significant differences between the two treatment groups for gender, age, side of affected lung, preoperative heart rate, history of beta-blocker use, coronary heart disease, and chronic obstructive pulmonary disease. Through logistic regression, EPP (OR=7.1, 95% CI: 2.9, 17.8) and age over 65 years (OR=2.9, 95% CI: 1.2, 6.8) were found to be risk factors for AF. We conclude that EPP vs. pleurectomy and age over 65 years are risk factors for postoperative AF. The increased odds of having AF after EPP could be due to right heart stress caused by pneumonectomy.

Chromosomal deletion in patients with malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is associated with frequent deletions of specific chromosomal regions within 1p, 3p, 6q, 9p, 13q, 15q, and 22q. In this retrospective review of our patients with MPM, the tumor tissue of 40 patients (31 male and 9 female) was evaluated for chromosomal deletions and was karyotyped. Chromosomal deletions in regions 1p, 3p, 6p, 9p, 6q, 9q, 22q were observed in 22 of 40 patients (55%). Of this group of 22 patients, 15 (68%) demonstrated deletions in chromosome 6; 12 (54%) exhibited deletions in chromosome 22q; and 13 (59%) had deletions in chromosome 9p. Asbestos exposure was found in only 13 of the 22 patients (59%) with chromosomal deletions. There was no correlation between asbestos exposure and chromosomal deletion (95% CI -0.38-0.23, P=0.63). Chromosomal deletion did not correlate with age (95% CI -0.45-0.14, P=0.29). The majority of patients with chromosomal deletions had epithelial histology (17 of 22 patients; 77%), which was not statistically significant (95% CI -0.14-0.46, P=0.27). Chromosomal deletion is common in tumor tissue of MPM and the inactivation of tumor suppressor genes (TSGs) residing in these chromosomes may contribute to mesothelial cell tumorigenesis.

Impact of pre-existing conditions, age and the length of cardiopulmonary bypass on postoperative outcome after repair of the ascending aorta and aortic arch for aortic aneurysms and dissections

BACKGROUND Repair of the ascending aorta and aortic arch carries a high morbidity and mortality, which can be complicated by the often emergent nature of the intervention. METHODS We retrospectively evaluated the morbidity, mortality, and long-term survival in 101 patients who underwent repair of ascending aorta and aortic arch. Depending on the urgency of the operation, the patients were categorized as elective (EL, n=82) or emergent (EM, n=19). Log-rank-list and SPS were used to evaluate the data. RESULTS The average age was 58+/-16 years. The aortic diameter was 5.5+/-1 cm in the EL group and 6.1+/-1.4 cm for EM group. The aortic dissection in EL and EM groups was 15% and 79%, respectively. The mean circulatory arrest time (n=32 patients) was 38+/-18.5 min. The overall 30-day mortality was 4%: 0% for the EL group and 26% for the EM group. The overall 6-month mortality was 8%: 3.7% and 26% in EL and EM groups, respectively. Overall CVA was 3%: 0% in the EL group and 15.7% in the EM group. The mean CPB time was 176+/-81 min. The prolonged CPB time correlated with increased need for blood transfusion. The LOS was 12+/-8 days and correlated with increasing age (95% CI 0.06860-0.2307, P=0.0004), with NYHA stage of patients at the time of surgery (95% confidence intervals, 1.328-4.202, P=0.0003), with left ventricular ejection fraction (95% CI 0.2357 to -0.003029, P=0.0442) and with postoperative atrial fibrillation (95% CI 0.1192-0.4745, P=0.0018). The average ICU stay was 123+/-145 h. A prolonged CPB time resulted in extended ICU stay (95% CI 0.3655-1.486, P=0.0014). Further, the length of ICU stay correlated with NYHA status (95% CI 19.98-73.42, P=0.0008), age (95% confidence intervals 0.01668-3.761, P=0.0477), urgency of surgery (95% CI 65.00-124.0, P<0.0001), and length of CPB time (95% CI 0.3655-1.486, P=0.0014). CONCLUSION Emergent operations are associated with high morbidity and mortality. Pre-existing heart failure, advanced age, and prolonged cardiopulmonary bypass are associated with prolonged monitoring in the ICU.

A novel technique for en bloc, vascularized, composite thymic, and cardiac co-transplantation1

Background. A surgical technique for co-transplantation of fully vascularized thymus and heart potentially applicable to the clinical setting has not been developed and is the subject of this article. Methods. Vascularized right lobe of the thymus was transplanted heterotopically with the heart as a composite graft in rats. This co-transplantation technique was developed and assessed, and viability of the grafted thymus was evaluated histologically. Results. Surgical mortality was identical to isolated heart transplantation, and all grafted hearts functioned well. Histology of the thymic grafts at explantation revealed viable thymus with preservation of normal thymic microarchitecture. Conclusion. We developed a novel technique to create a composite graft in which fully vascularized and viable thymus was harvested en bloc and co-transplanted with a donor heart allograft.

Autologous blood sequestration using a double venous reservoir bypass circuit and polymerized hemoglobin prime.

Cardiac surgery often necessitates transfusion of homologous blood. Hemoglobin based oxygen carrying solutions (HBOCs) transport oxygen, suggesting use in cardiopulmonary bypass. HBOC was used in a novel oxygenator double-reservoir circuit that permits acute sequestration of a portion of the autologous blood volume during bypass. Two groups of seven mongrel dogs each were studied in an experimental bypass model using global myocardial ischemia and cardioplegia protection: HBOC group, initial venous return drained to a separate reservoir and hypothermic bypass was conducted with HBOC containing perfusate in a second bypass reservoir; Control group, crystalloid prime in a conventional circuit. Hemodynamics and metabolic and hematologic parameters were measured before and 60 min after aortic clamp removal and reinfusion of sequestered autologous blood. Blood gases, base excess, hematocrit, total hemoglobin, and platelet counts were measured. In the HBOC group, metabolic acidosis did not occur, and ventricular function was preserved. Net conservation of platelets was noted at study conclusion: control 33 ± 13 × 103 per mm3versus HBOC 48 ± 13 × 103, p < 0.05. HBOC based priming in a double venous reservoir system permits bypass at very low hematocrit, with preservation of cardiac function. Net conservation of the platelet mass occurs, a portion of which is not exposed to the deleterious effects of hypothermia and cardiopulmonary bypass.

Retraction: Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors

BioMed Central is publishing a retraction of this article [1] as the article was published in error. BioMed Central apologize to the authors for the error and any inconvenience caused. An apology is also extended to the readers.