Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers.

BACKGROUND: The BRCA1/2 proteins are involved in regulation of cellular proliferation by DNA damage repair via homologous recombination. Therefore, BRCA1/2 mutation carriers with pancreatic cancer may have distinct biologic outcomes. METHODS: Patients with BRCA1/2-associated pancreatic ductal adenocarcinoma (PDAC) diagnosed between January 1994 and December 2012 were identified from databases at three participating institutions. Clinical data were collected. Disease-free survival and overall survival (OS) were analysed. RESULTS: Overall, 71 patients with PDAC and BRCA1 (n=21), BRCA2 (n=49) or both (n=1) mutations were identified. Mean age at diagnosis was 60.3 years (range 33-83), 81.7% (n=58) had any family history of malignancy; 30% (n=21) underwent primary resection. Out of 71 participants, 12 received experimental therapy; one patient had missing data, these 13 cases were excluded from OS analysis. Median OS for 58 patients was 14 months (95% CI 10-23 months). Median OS for patients with stage 1/2 disease has not been reached with 52% still alive at 60 months. Median OS for stage 3/4 was 12 months (95% CI 6-15). Superior OS was observed for patients with stage 3/4 treated with platinum vs those treated with non-platinum chemotherapies (22 vs 9 months; P=0.039). CONCLUSION: Superior OS was observed for advanced-disease BRCA-associated PDAC with platinum exposure.

Lymphocyte blastogenic response to ovalbumin in a model for canine allergy.

Lymphocyte stimulation tests (LST) were performed in five dogs sensitised with ovalbumin (OVA) and seven healthy dogs. In addition, all five OVA-sensitised and two control dogs were tested after two in vivo provocations with OVA-containing eye drops. The isolated cells were suspended in culture media containing OVA and were cultured for up to 12 days. Proliferation was measured as reduction in 5,6-carboxylfluorescein diacetate succinimidyl ester (CFSE) intensity by flow cytometry on days 0, 3, 6, 9 and 12. A cell proliferation index (CPI) for each day and the area under the curve (AUC) of the CPI was calculated for each dog. All OVA-sensitised dogs demonstrated increased erythema after conjunctival OVA application. The presence of OVA-specific lymphocytes was demonstrated in 2/5 OVA-sensitised dogs before and 4/5 after in vivo provocation. Using the AUC, the difference between OVA-sensitised and control dogs was significant in all three LST before in vivo provocation (P<0.05) and borderline significant (P=0.053) in 2/3 LST after provocation. The most significant difference in CPI was observed after 9 days of culture (P=0.001). This pilot study indicates that the LST allows detection of rare antigen specific memory T-cells in dogs previously sensitised to, but not concurrently undergoing challenge by a specific antigen.

Gastrojejunal anastomotic stricture after Roux-en-Y gastric bypass: ambulatory management with the Savary-Gilliard dilator.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is currently one of the most frequently performed procedures for the surgical treatment of morbid obesity. The success of this procedure's restrictive component requires a small gastrojejunostomy (GJ), which occasionally results in stenosis. The treatment of choice for this complication is balloon dilation. This study aimed to evaluate the feasibility and safety of ambulatory management for stenosis of the GJ using endoscopically guided Savary-Gilliard dilators. METHODS: Between January 1998 and October 2003, 769 patients underwent RYGBP. The mean age of these patients was 38 +/- 12 years, and their mean body mass index (BMI) was 43 +/- 6 kg/m2. Of these 769 patients, 520 (68%) underwent open surgery and 249 (32%) underwent laparoscopic RYGBP. Patients suspected of GJ stenosis were referred for upper gastrointestinal endoscopy. Those who presented with stenosis were managed endoscopically with Savary-Gilliard dilators. RESULTS: Stenosis at the GJ was confirmed in 53 patients (6.9%). A total of 71 dilations were performed for these patients, resulting in a mean of 1.3 dilations per patient. One dilation was needed for 41 patients (75.5%), two dilations for 9 patients (16.9%), three dilations for 3 patients (5.7%), and four dilations 1 patient (1.9%). The patients subjected to open RYGBP required a mean of 1.57 dilations, and those who had laparoscopic RYGBP required mean of 1.08 dilations. The mean time for the first dilation was 51 +/- 28 days after surgery (range, 20-178 days). All the dilations were performed in ambulatory settings. One patient (1.9%) was admitted after GJ dilation for pain. He was discharged without symptoms after 2 days with no need for invasive procedures. CONCLUSIONS: The management and treatment of GJ stenosis after RYGBP can be effectively accomplished in ambulatory settings using endoscopically guided Savary-Gilliard dilators, with good and safe results.

Chemotherapy of MMR-deficient colorectal cancer.

Colorectal cancer (CRC) continues to rank as the third most common cancer in Western society and the second leading cause of cancer death in North America. There are at least three distinct, and relatively discreet, molecular pathways associated with this disease: chromosomal instability (CIN), microsatellite instability (MSI) and the cytosine polyguanine island methylator phenotype. Defects in the DNA mismatch repair system (MMR) account for the MSI phenotype and genotype of about 15 % of CRC. Although high frequency MSI tumors have better stage independent prognosis compared to those with CIN, MMR deficient CRC appears to be resistant to fluorouracil based treatment, but sensitive to other therapeutic regimens. This review summarises current literature on differential chemosensitivity of MMR-deficient CRC.