Molecular profiling of stroma highlights stratifin as a novel biomarker of poor prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer worldwide, as a result of a late diagnosis and limited therapeutic options. Tumour microenvironment (or stroma) plays a key role in cancer onset and progression and constitutes an intrinsic histological hallmark of PDAC. Thus we hypothesised that relevant prognostic biomarkers and therapeutic targets can be identified in the stroma. METHODS: Laser microdissection of the stroma from freshly frozen PDAC was combined to gene expression profiling. Protein expression of candidate biomarkers was evaluated by immunohistochemistry on tissue microarrays (n = 80 tumours) and by ELISA in plasma samples (n = 51 patients). RESULTS: A signature made of 1256 genes that significantly discriminate the stroma from the non-tumour fibrous tissue was identified. Upregulated genes were associated with inflammation and metastasis processes and linked to NF-Kappa B and TGFß pathways. TMA analysis validated an increased expression of SFN, ADAMTS12 and CXCL3 proteins in the stroma of PDAC. Stromal expression of SFN was further identified as an independent prognostic factor of overall (p = 0.003) and disease-free survival (DFS) (p = 0.034). SFN plasma expression was significantly associated with reduced DFS (p = 0.006). CONCLUSIONS: We demonstrated that gene expression changes within the stroma of PDAC correlate with tumour progression, and we identified Stratifin as a novel independent prognostic biomarker.

Impact of adjuvant chemotherapy after pancreaticoduodenectomy for distal cholangiocarcinoma: a propensity score analysis from a French multicentric cohort.

BACKGROUND: The benefit of adjuvant chemotherapy (AC) after pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) remains controversial. The study aimed to evaluate the impact of AC after PD for DCC in a large multicentric cohort. METHODS: Patients from five French centers who underwent from PD for DCC between 2000 and 2015 and received AC (AC+ group) or surgery only (AC- group) were included in the analysis. Variables associated with AC administration were analyzed by univariate analysis. The Cox regression identified covariates associated with overall survival (OS) and disease-free survival (DFS). The AC+ cohort was matched to the AC- cohort (1:1) by a propensity score (PS) based on the likelihood of AC administration and independent factors associated with decreased OS and DFS. RESULTS: Of the 178 patients included, 56 (31.5%) received AC. In the whole cohort, no difference on OS and DFS between the AC+ and AC- groups was identified (P = 0.15 and P = 0.07, respectively). After PS matching, the AC+ group (n = 49) was comparable to the AC- group (n = 49) on factors associated with AC administration and on factors associated with a decreased survival in the large cohort. After matching, the medians of OS and DFS in the AC+ group and in the AC- group were comparable (26.27 vs 43.33 months, P = 0.34, and 15.47 vs. 14.70 months, P = 0.79, respectively). CONCLUSION: Our study did not demonstrate a survival benefit of adjuvant chemotherapy (mostly base on gemcitabine regimen) for DCC after PD even after propensity score matching. New trial specially designed for DCC is urgently needed to improve survival after surgical resection.

Is systematic nasogastric decompression after pancreaticoduodenectomy really necessary?

BACKGROUND: Since the spread of enhanced recovery programs, early withdrawal of the nasogastric tube (NGT) is recommended after pancreaticoduodenectomy (PD), although few data on the safety of this practice are available. The aim of the present study was to evaluate the absence of nasogastric decompression after PD on postoperative outcome. STUDY DESIGN: All consecutive patients undergoing PD between January 2014 and December 2015 at a single center were retrospectively analyzed. Since May 2015, all operated patients had the NGT removed immediately after the procedure (NGT- group) and were compared to patients operated before this practice (NGT+ group), who had the NGT maintained until at least postoperative day 3. RESULTS: During the study period, 139 patients underwent PD, of whom 40 (29%) were in the NGT- group and 99 (71%) were in the NGT+ group. The length of hospital stay (LOS) and rate of postoperative complications of grade 2 or higher according to the Clavien-Dindo grading system were significantly higher in the NGT+ group [14 (11-25) vs. 10 (8-14.2), P = 0.005 and 82.8 vs. 40%, P < 0.001, respectively]. Incidence and severity of delayed gastric emptying (DGE) grade B-C were also higher in the NGT+ group (45.5 vs. 7.5%, P < 0.001). There was no difference between the two groups concerning the 90-day postoperative mortality (P = 0.18). CONCLUSION: The absence of systematic nasogastric decompression after PD might reduce postoperative complications, DGE, and LOS. These encouraging results deserve to be confirmed by a prospective randomized study (NCT: 02594956).

Multicentre study of the impact of factors that may affect long-term survival following pancreaticoduodenectomy for distal cholangiocarcinoma.

BACKGROUND: Although the peri-operative mortality following pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) has decreased, the post-operative morbidity remains high. The aim of this study was to evaluate the impact of factors that may affect the long term survival for patients with DCC following PD. METHODS: All patients who underwent PD for DCC between January 2000 and December 2015 in 5 tertiary referral centers underwent retrospective medical record review. Factors likely to influence overall (OS) and disease-free (DFS) survivals were assessed by univariate and multivariate analysis. RESULTS: A total of 201 on 217 patients who underwent PD for DCC were included for further analysis. The median OS was 39 months, with actuarial survival rates at 1, 3, and 5 years of 85%, 53% and 39%. Recurrence occurred in 123 (61%) patients. The median DFS was 16 months, with actuarial survival rates at 1, 3 and 5 years of 60%, 37% and 28%. Following multivariate analysis, peri-operative blood transfusions (PBT) were associated to worse OS (HR = 2.25 [1.31-3.85], P = 0.003) and DFS (HR = 2.08 [1.24-3.5], P = 0.005). CONCLUSION: This study confirms the negative impact of PBT on the oncologic result following PD for DCC.

Frey procedure combined with biliary diversion in chronic pancreatitis.

BACKGROUND: The Frey procedure has become the standard operative treatment in chronic painful pancreatitis. Biliary diversion could be combined when associated with common bile duct obstruction. The aim of the present study was to evaluate the impact of the type of biliary diversion combined with the Frey procedure on late morbidity. METHODS: The data from consecutive patients undergoing the Frey procedure and having a minimum follow-up of 2 years were extracted from a maintained prospective database. The mean endpoint was the rate of secondary biliary stricture after the Frey procedure combined with biliary diversion (bilioenteric anastomosis or common bile duct reinsertion in the resection cavity). RESULTS: Between 2006 and 2013, 55 consecutive patients underwent the Frey procedure. Twenty-nine patients had common bile duct obstruction (52.7%). The technique of biliary diversion resulted in bilioenteric anastomosis in 19 patients (65.5%) and common bile duct reinsertion in 10 patients (34.5%). Preoperative characteristics and early surgical outcomes were comparable. Pain control was similar. There was significantly more secondary biliary stricture after common bile duct reinsertion than after bilioenteric anastomosis (60% vs 11%, P = .008). CONCLUSION: Combined bilioenteric anastomosis during the Frey procedure is an efficient technique for treating common bile duct obstruction that complicates chronic painful pancreatitis. Bilioenteric anastomosis was associated with less secondary biliary stricture than common bile duct reinsertion in the pancreatic resection cavity.

The true prognosis of resected distal cholangiocarcinoma.

BACKGROUND: Prognosis of distal cholangiocarcinoma (DCC) after pancreaticoduodenectomy (PD) remains poorly assessed. The aims of this study were to describe the oncological results of PD in DCC and to compare its prognosis to pancreatic ductal adenocarcinoma (PDAC). METHODS: All PD for periampullary carcinoma performed between January 2000 and March 2013 were extracted from a prospective database. Risk factors likely to influence overall (OS) and disease-free (DFS) survivals of DCC were assessed by multivariable analyses. The DCC and PDAC prognoses were compared after matching using propensity score (nearest neighbor matching). RESULTS: Of the 290 patients analyzed, 56 had DCC, with a mean age of 65 ± 15 years. The median OS was 36.9 months. Recurrence occurred in 35 patients (67%), mostly in the liver (37%). The median DFS was 14.6 months. Combined organ resection was an independent risk factor for worse OS and DFS (P = 0.01 and P = 0.001, respectively). Matching analysis found no significant difference between DCC and PDAC in terms of OS (P = 0.284) or DFS (P = 0.438). CONCLUSION: This first propensity analysis demonstrated that DCC and PDAC have the same prognosis, linked to the high rate of early recurrence, particularly associated with the need for combined organ resection. J. Surg. Oncol. 2016;113:575-580. © 2016 Wiley Periodicals, Inc.