Reflex Testing for Germline BRCA1, BRCA2, PALB2, and ATM Mutations in Pancreatic Cancer: Mutation Prevalence and Clinical Outcomes From Two Canadian Research Registries.

PURPOSE: We investigated the translational value of reflex testing for germline mutations in four homology-directed DNA repair predisposition genes (BRCA1, BRCA2, PALB2, and ATM) in consecutive patients with pancreatic adenocarcinoma. METHODS: One hundred fifty patients with French-Canadian (FC) ancestry were evaluated for founder mutations, and 114 patients were subsequently assessed by full gene sequencing and multiplex ligation-dependent probe amplification for nonfounder mutations. Two hundred thirty-six patients unselected for ancestry were also assessed for mutations by full gene sequencing. RESULTS: The FC founder mutation prevalence among the 150 patients was 5.3% (95% CI, 2.6% to 10.3%), and the nonfounder mutation prevalence across the four genes among the 114 patients tested was 2.6% (95% CI, 0.6% to 7.8%). In the case series unselected for ancestry, 10.0% (95% CI, 2.7% to 26.4%) of patients reporting Ashkenazi Jewish (AJ) ancestry carried an AJ founder mutation, with no nonfounder mutations identified. The mutation prevalence among patients without FC/AJ ancestry was 4.9% (95% CI, 2.6% to 8.8%). Mutations were more frequent in patients diagnosed at ≤ 50 years of age (P = .03) and in patients with either two or more first- or second-degree relatives with pancreas, breast, ovarian or prostate cancer, or one such relative and a second primary of one of these cancer types (P < .001). BRCA1, BRCA2, and PALB2 carriers with late-stage (III or IV) disease had an overall survival advantage (P = .049), particularly if treated with platinum-based chemotherapies (P = .030). CONCLUSION: Considering these results, we recommend reflex founder mutation testing of patients with FC/AJ ancestry and full gene sequencing of patients who are ≤ 50 years or meet the identified family history criteria. Reflex testing of all incident patients for these four genes may become justified as full gene sequencing costs decline.

High frequency ventilation combined with spontaneous breathing during bronchopleural fistula repair: a case report.

PURPOSE: We report the addition of high frequency oscillatory ventilation (HFOV), combined with spontaneous breathing under general anesthesia, during an uncommon technique to occlude a late post-pneumonectomy bronchopleural fistula. CLINICAL FEATURES: A 41-year-old woman underwent an extended right pneumonectomy with chest wall resection and prosthetic reconstruction for a large adenocarcinoma of the upper lobe (T3N0M0). Her postoperative recovery was satisfactory, and she subsequently received adjuvant chemotherapy. Four months later, however, she was readmitted for investigation of confusion and pink expectorations. On cerebral magnetic resonance imaging, a frontal metastasis with surrounding edema was discovered, as well as a possible secondary lesion in the occipital lobe. In view of the comorbidities, thoracoscopy was planned as an interim measure, with the goal being to debride the fistula and to seal the prosthetic plug. During this case, a HFOV system was used to allow an addition of 2.5 L.min(-1) of minute ventilation to the patient's spontaneous respiration, while maintaining eucapnia without increasing airway pressure. CONCLUSIONS: With the addition of high frequency ventilation under general anesthesia in a patient with a persistent bronchopleural fistula, the PaCO(2) level was adequately controlled during the simultaneous use of fibreoptic bronchoscopy and video assisted thoracoscopy to facilitate a successful surgical repair.

Specific roles of the obstetrician-gynecologist.

Obstetrician-gynecologists can play a major role in the prevention, identification, and treatment of substance abuse in women. Maintaining cognizance of abuse potential and consistently using office-screening techniques will identify patients who need assistance. Employing brief interventions at frequent office visits is an effective means of treating many of these patients. Those who do not respond to brief interventions may benefit from referral to an addictionologist. The US Supreme Court recently verified the Fourth Amendment rights of pregnant women by deciding that consent must be obtained to perform drug screening in pregnancy. Obstetrician-gynecologists will need to stay abreast of the changes that occur in their state laws as a result of this decision.