A transcriptomic signature to predict adjuvant gemcitabine sensitivity in pancreatic adenocarcinoma.

BACKGROUND: Chemotherapy is the only systemic treatment approved for pancreatic ductal adenocarcinoma (PDAC), with a selection of regimens based on patients' performance status and expected efficacy. The establishment of a potent stratification associated with chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments. PATIENTS AND METHODS: Concomitant chemosensitivity and genome-wide RNA profiles were carried out on preclinical models (primary cell cultures and patient-derived xenografts) derived from patients with PDAC included in the PaCaOmics program (NCT01692873). The RNA-based stratification was tested in a monocentric cohort and validated in a multicentric cohort, both retrospectively collected from resected PDAC samples (67 and 368 patients, respectively). Forty-three (65%) and 203 (55%) patients received adjuvant gemcitabine in the monocentric and the multicentric cohorts, respectively. The relationships between predicted gemcitabine sensitivity and patients' overall survival (OS) and disease-free survival were investigated. RESULTS: The GemPred RNA signature was derived from preclinical models, defining gemcitabine sensitive PDAC as GemPred+. Among the patients who received gemcitabine in the test and validation cohorts, the GemPred+ patients had a higher OS than GemPred- (P = 0.046 and P = 0.00216). In both cohorts, the GemPred stratification was not associated with OS among patients who did not receive gemcitabine. Among gemcitabine-treated patients, GemPred+ patients had significantly higher OS than the GemPred-: 91.3 months [95% confidence interval (CI): 61.2-not reached] versus 33 months (95% CI: 24-35.2); hazard ratio 0.403 (95% CI: 0.221-0.735, P = 0.00216). The interaction test for gemcitabine and GemPred+ stratification was significant (P = 0.0245). Multivariate analysis in the gemcitabine-treated population retained an independent predictive value. CONCLUSION: The RNA-based GemPred stratification predicts the benefit of adjuvant gemcitabine in PDAC patients.

Adrenocortical carcinoma surgery-surgical extent and approach.

PURPOSE: Adequate tumour resection is the gold standard of care for adrenocortical carcinoma (ACC). However, the optimal surgical strategy remains debatable. In our opinion, the extent of surgery (adequate tumour resection) is the primary concern, rather than the surgical approach (laparoscopic or open). We propose that both surgical approaches have a role in the management of ACC provided the extent of resection is selected based on patient and tumour characteristics and accurate pre-operative investigations. METHODS: A review of 25 curative intent resections for ACC between 2002 and 2013 was done. Group A (16 patients-64 %) included all patients who underwent planned radical adrenalectomy without any other resection and group B (9 patients-36 %) included all patients who underwent a planned extensive resection based on pre-operative investigations. RESULTS: Of 471 adrenalectomies, 25 were performed for ACC with curative intent. Tumours were significantly larger in group B with mean size of 119.6 versus 62.4 mm in group A (p = 0.002). Tumours in group B also had higher WEISS scores (mean score 7 vs 5.2, p = 0.033) and almost always required multi-organ resection. The recurrence rate was 37.5 % (n = 6) for group A and 44.4 % for group B (n = 4), p = 1.00. Poor prognosis was associated with significantly higher WEISS scores (p = 0.016) and a trend towards more advanced ENSAT disease stage (p = 0.06). Estimated overall survival was 74.17 months (group A 67.3 vs group B 70.1, p = 0.244). CONCLUSIONS: Accurate pre-operative staging is critical to select a tailored surgical strategy. Multi-organ resection remains the preferred approach for large and potentially invasive ACC. Some patients presenting with smaller ACC may benefit from a more extensive resection.

In situ revascularization with rifampicin-soaked silver polyester graft for aortic infection: Results of a retrospective monocentric series of 18 cases.

OBJECTIVE: To evaluate the short and long-term results of in situ prosthetic graft treatment using rifampicin-soaked silver polyester graft in patients with aortic infection. MATERIAL AND METHOD: All the patients surgically managed in our center for an aortic infection were retrospectively analyzed. The primary endpoint was the intra-hospital mortality, secondary outcomes were limb salvage, persistent or recurrent infection, prosthetic graft patency, and long-term survival. RESULTS: From January 2004 to December 2015, 18 consecutive patients (12 men and 6 women) were operated on for aortic infection. Six mycotic aneurysms and 12 prosthetic infections, including 8 para-entero-prosthetic fistulas, were treated. In 5 cases, surgery was performed in emergency. During the early postoperative period, we performed one major amputation and two aortic infections were persistent. Intra-hospital mortality was 27.7%. The median follow-up among the 13 surviving patients was 26 months. During follow-up, none of the 13 patients presented reinfection or bypass thrombosis. CONCLUSION: This series shows that in situ revascularization with rifampicin-soaked silver polyester graft for aortic infection have results in agreement with the literature in terms of intra-hospital mortality with a low reinfection rate.

Management of delayed stenosis of pancreatico-enteric anastomosis following pancreatoduodenectomy.

Stenosis of the pancreatico-enteric anastomosis following pancreatoduodenectomy (PD), a late post-operative complication that is seen mainly after PD for diseases with good prognosis, has been reported in less than 3% of cases in the literature. Most often asymptomatic, pancreatic-enteric anastomotic stenosis can lead to pancreatitis, pain or pancreatic insufficiency. Symptomatic stenosis is difficult to treat and its management is not standardized. Magnetic resonance cholangiopancreatography is the best investigation to confirm the diagnosis of stenosis. The Endoscopic UltraSonography (EUS) « rendezvous ¼ technique, associating an endoscopic approach and EUS-guided puncture of the main pancreatic duct, has been available since 2010. Of note, however, the failure rate of the EUS series is as high as 25%, leading to repeat procedures. Surgical reconstruction of the anastomosis has been reported with good results in terms of morbidity. Surgical re-do of the pancreatico-enteric anastomosis for stenosis following PD carries a low risk of pancreatic fistula (around 5%) and an overall morbidity rate of around 20%.