Raja M. Flores

Absence of detectable PML-RARα fusion transcripts in long-term remission patients after BMT for acute promyelocytic leukemia

Twenty patients with APL in long-term remission after BMT were analyzed for the presence of the PML-RARα x fusion gene by RT-PCR. Ten patients had undergone autologous BMT (six of them peripheral blood stem cell transplantation) and 10 allogeneic BMT. A total of 60 samples were examined by two different protocols. Of the eight patients studied just before conditioning, five showed PML-RARα transcript prior to transplantation. Three of them were in CR and became PCR negative early post-transplantation. The other two patients, that were not in CR before transplant, remained PCR positive, relapsed early post-transplant and died. In the remaining patients no PML-RARα transcripts were visible throughout their post-BMT courses. Our data show that long-term remission after BMT in APL patients is associated with eradication of cells carrying the PML-RAR α transcript, and that continued positivity of this test predicts subsequent relapse. The fact of the disappearance of PML-RARα transcript early after BMT in patients previously positive suggest that transplant is capable of curing APL mainly through antileukemic action of the conditioning regimen and therefore, transplantation must be indicated in CR patients if a positive RT-PCR remains after treatment with ATRA plus chemotherapy.

Women with malignant pleural mesothelioma have a threefold better survival rate than men.

BACKGROUND Many studies have reported that women with malignant pleural mesothelioma (MPM) experience longer survival compared with men, whereas others have not. To date, no large population-based studies have evaluated MPM outcome and its determinants in female patients. METHODS All pathologically confirmed cases of MPM in the Surveillance, Epidemiology and End Results database from 1973 to 2009 were evaluated. Age, year of diagnosis, race, stage, cancer-directed surgery, radiation, and vital status were analyzed according to gender. Cox proportional hazard models were derived to assess the association between prognostic factors and survival. RESULTS There were 14,228 cases of MPM, of which 3,196 (22%) were women. Despite similar baseline characteristics for both genders, 5-year survival was 13.4% in women and 4.5% in men (p < 0.0001). The effect of female gender on survival persisted when stratified by age (dichotomized at 50 years), stage, or race, but differed depending on treatment. Even when adjusted for age, stage, race, and treatment, female MPM patients experienced longer survival than men (hazard ratio = 0.78; 95% confidence interval 0.75 to 0.82). CONCLUSIONS This large data set confirms that although MPM is less common in women, they present with similar stage and are offered similar treatment options compared with men. Nevertheless, survival is far better in women compared with men, independent of confounders such as age, stage, and treatment. Differences in asbestos exposure, tumor biology, and the impact of circulating hormones on host response must be investigated to understand this survival advantage and improve prognosis for patients of both genders.

Pleurectomy decortication for mesothelioma: The procedure of choice when possible.

From the Department of Thoracic Surgery, Icahn School of Medicine, Mount Sinai Health System, NewYork, NY. Disclosures: Author has nothing to disclose with regard to commercial support. Received for publication Oct 9, 2015; accepted for publication Oct 13, 2015; available ahead of print Nov 21, 2015. Address for reprints: Raja M. Flores, MD, Department of Thoracic Surgery, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1023 New York, NY 10029 (E-mail: raja.flores@mountsinai.org). J Thorac Cardiovasc Surg 2016;151:310-2 0022-5223/

Pulmonary abnormalities as a result of exposure to Libby amphibole during childhood and adolescence—The pre-adult latency study (PALS)

36.00 Copyright 2016 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2015.10.036

Thymectomy for Myasthenia Gravis: Complete Stable Remission and Associated Prognostic Factors in Over 1000 Cases

BACKGROUND The purpose of Pre-Adult Latency Study was to evaluate lung findings among adults who had been environmentally exposed to Libby Amphibole only during childhood and adolescence. METHODS Recruitment was restricted to volunteers who attended primary and/or secondary school, lived in Libby, MT, prior to age 23 years for males and 21 years for females and subsequently left the area. Subjects completed exposure and respiratory questionnaires, underwent pulmonary function tests (PFTs), and chest CT scans. A Pleural Score was calculated for degree and extent of pleural thickening. Logistic regression and multivariate linear regression were used. RESULTS Of the 219 who met inclusion criteria, 198 participated. Pleural thickening was found in 96 (48%) of 198 participants. In almost half of these, it was of the lamellar type, not generally seen in exposure to other asbestos. Environmental Libby amphibole exposure was associated with pleural thickening, and the likelihood of pleural thickening increased with the number of years lived in the area. An inverse association between Pleural Score and PFT was found, which remained significant for FVC and DLco after additional sensitivity analyses. CONCLUSIONS Cumulative environmental exposure was associated with risk of pleural thickening. Among this cohort, quantitative measures of pleural thickening were associated with decreased PFT. Am. J. Ind. Med. 60:20-34, 2017.

Molecular Heterogeneity in Childhood Precursor B Acute Lymphoblastic Leukemia with Immunoglobulin Heavy Chain Gene in Germline Configuration

The efficacy of thymectomy and the optimal surgical technique in the treatment of myasthenia gravis (MG) remain controversial. Long-term outcomes are lacking and remission rates are based on small populations. We reviewed our institutional experience of thymectomy for MG focusing on long-term outcomes, complete stable remission (CSR), improvement of symptoms, after transcervical, transsternal, thoracotomy, and VATS thymectomy. A retrospective review of a prospectively maintained database of 3017 patients from 1941-2013 with MG was performed. Patients who underwent thymectomy with follow-up data including age at the time of surgery, sex, date of onset of symptoms, date of surgery, Osserman classification before and after surgery, surgical technique, date of remission, and status at last follow-up were included in the analysis. CSR and prognostic factors were analyzed by crude rate, Kaplan-Meier estimate, chi-squared test, Wilcoxon test, and a Cox proportional model. Overall, 1002 thymectomy patients with complete data were analyzed, and 35.5% (n = 355) derived benefit from surgery. Crude rate CSR was 19% (n = 191) and an additional 16% (n = 164) symptomatically improved requiring less medication after thymectomy. Also, 58% (n = 580) were stable after resection, and 6.7% (n = 67) developed progressive disease. Kaplan-Meier estimates of CSR were 27.7%, 36.7%, and 47.3% at 10, 25, and 40 years, respectively. On multivariate analysis, transsternal technique, thymoma, and preoperative Osserman classification were significantly associated with failure to achieve CSR. Thymectomy provides long-term CSR in 47.3% of patients with long-term follow-up. Patients with MG should be offered thymectomy when possible.

The mesothelioma surgery shift

Four childhood acute leukemias with morphological, cytochemical and immunological characteristics correlating to precursor B lymphocyte and with germline configuration of the immunoglobulin heavy chain joining region were studied for the organization of the C mu segment. Two of the four lymphoblast samples retained the germline configuration of both JH and C mu regions. The other two samples showed delection of the entire JH region resulting in the rearrangement of the C mu region. In contrast to patients with C mu rearrangement, patients with C mu in germline form were not able to achieve complete remission after induction therapy. Study of the C mu region in patients with JH segment in germline configuration could separate subgroups in childhood precursor B acute lymphoblastic leukemia with different prognoses.