TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: 5-year survival for melanoma metastasis to regional lymph nodes (American Joint Committee on Cancer stage III) is <50%. Knowledge of outcomes following therapeutic lymphadenectomy for stage III melanoma related to BRAF status may guide adjuvant use of BRAF/MEK inhibitors along with established and future therapies.', 'To determine patterns of melanoma recurrence and survival following therapeutic lymph node dissection (TLND) associated with oncogenic mutations.', 'DNA was obtained from patients who underwent TLND and had ⩾2 positive nodes, largest node >3cm or extracapsular invasion. Mutations were detected using an extended Sequenom MelaCARTA panel.', 'Mutations were most commonly detected in BRAF (57/124 [46%] patients) and NRAS (26/124 [21%] patients). Patients with BRAF mutations had higher 3-year recurrence rate (77%) versus 54% for BRAF wild-type patients (hazard ratio (HR) 1.8, p=0.008). The only prognostically significant mutations occurred in BRAF: median recurrence-free (RFS) and disease-specific survival (DSS) for BRAF mutation patients was 7 months and 16 months, versus 19 months and not reached for BRAF wild-type patients, respectively. Multivariate analysis identified BRAF mutant status and number of positive lymph nodes as the only independent prognostic factors for RFS and DSS.\Question: Is bRAF mutation status an independent prognostic factor for resected stage IIIB and IIIC melanoma : implications for melanoma staging and adjuvant therapy?

SOLUTION: Patients with BRAF mutations experienced rapid progression of metastatic disease with locoregional recurrence rarely seen in isolation, supporting incorporation of BRAF status into melanoma staging and use of BRAF/MEK inhibitors post-TLND.

PROBLEM: Context: To demonstrate the effect in vivo of the myocilin gene mutation Thr377Met on outflow facility of aqueous humor, as measured by tonography.', 'Forty-two members of a pedigree known to carry the Thr377Met mutation were examined for glaucoma, evaluated with tonography, and screened for myocilin mutations. Tonography was used to calculate the coefficient of aqueous outflow facility (C), as well as the ratio of the resting intraocular pressure to C (P(0)/C). Subjects were reexamined for glaucoma 5 years after tonography.', "Seven subjects were excluded because of previous treatment known to alter facility of aqueous outflow. The mean outflow facility of the eyes of the 12 subjects carrying the Thr377Met mutation was significantly reduced compared with the 23 non-carriers' eyes using both C (P<0.001) and P(0)/C (P<0.001). Reduced outflow facility was also demonstrated in those mutation carriers who were not yet expressing clinical signs of glaucoma or ocular hypertension when measured using C (P = 0.015) and P(0)/C (P = 0.001). After 5 years, progression towards glaucoma had occurred in 5 of the myocilin mutation-carriers, 2 of whom showed bilateral progression; 3 carriers remained completely normal. Four subjects had bilateral glaucoma at the outset and remained unchanged. The carriers' eyes that progressed towards glaucoma had reduced outflow facility compared with those that remained normal, although the difference was not statistically significant.\Question: Does tonography demonstrate reduced facility of outflow of aqueous humor in myocilin mutation carriers?

SOLUTION: Carriers of the myocilin Thr377Met mutation have reduced outflow facility, which may be detected prior to developing glaucoma. Tonography was not seen to be clinically useful in predicting progression towards glaucoma.

PROBLEM: Context: Previous studies have proved the feasibility of performing a pancreaticoduodenectomy (Whipple operation) in patients with portal vein-superior mesenteric vein and hepatic artery invasion. We report our institutional experience with the use of a variety of vascular reconstructive methods during pancreatic resections for adenocarcinoma.', 'A retrospective review was performed identifying all patients undergoing a Whipple operation or total pancreatectomy procedure from January 2003 to December 2013. All venous (portal vein-superior mesenteric vein) and arterial (superior mesenteric artery-hepatic artery) reconstructions were extracted and reviewed to determine survival and perioperative complications.', 'During the 10-year study period, 270 Whipple and total pancreatectomy procedures were performed, of which 183 were for adenocarcinoma of the pancreas. Of the 183 operations, a total of 60 (32.8%) vascular reconstructions were found, 49 venous and 11 arterial. Venous reconstruction included 37 (61.7%) primary repairs, four (6.7%) reconstructions with CryoVein (CryoLife, Inc, Kennesaw, Ga), three (5.0%) repairs with autologous vein patch, three (5.0%) autologous saphenous reconstructions, and two (3.33%) portacaval shunts. In addition, there were 11 (18.3%) arterial reconstructions (seven hepatic artery and four superior mesenteric artery). The 1-year survival for all reconstructions was 71.1%, which is equivalent to T3 lesions that did not receive vascular reconstruction (70.11%), with a median survival time of 575.28 days and 12 patients still alive. Survival time was comparable with each type of venous reconstruction, averaging 528 days (11 of 49 patients still alive). There was a total thrombosis rate of seven of 60 (11.6%), all of which were portal vein thrombosis: three in the primary repair group and four delayed thromboses seen in primary repair, CryoVein repair, and vein patch repair. There was no thrombosis in any patients after arterial reconstruction.\Question: Does vascular reconstruction play an important role in the treatment of pancreatic adenocarcinoma?

SOLUTION:
An aggressive approach for stage II pancreatic cancers with venous or arterial invasion can be performed with comparable results when it is executed by an experienced institution with skilled oncologic and vascular surgeons.