• ERAS
• Pancreatic cancer
• Pancreaticoduodenectomy
• Sarcopenia
• Surgical outcomes

• International Study Group of Pancreatic Surgery
• pancreatic fistula
• pancreaticoduodenectomy
• prediction model

• China–Japan Friendship Hospital

• Borderline resectable
• Lymph node ratio
• Neoadjuvant therapy
• Pancreatic cancer
• Vein resection

To explore the relationship between the lymph node status and preoperative computed tomography images texture features in pancreatic cancer.

A total of 155 operable pancreatic cancer patients (104 men, 51 women; mean age 63.8 ± 9.6 years), who had undergone contrast-enhanced computed tomography in the arterial and portal venous phases, were enrolled in this retrospective study. There were 73 patients with lymph node metastases and 82 patients without nodal involvement. Four different data sets, with thin (1.25 mm) and thick (5 mm) slices (at arterial phase and portal venous phase) were analysed. Texture analysis was performed by using MaZda software. A combination of feature selection algorithms was used to determine 30 texture features with the optimal discriminative performance for differentiation between lymph node positive and negative groups. The prediction performance of the selected feature was evaluated by receiver operating characteristic (ROC) curve analysis.

There were 10 texture features with significant differences between two groups and significance in ROC analysis were identified. They were WavEnLH_s-2(wavelet energy with rows and columns are filtered with low pass and high pass frequency bands with scale factors 2) from wavelet-based features, 135dr_LngREmph (long run emphasis in 135 direction) and 135dr_Fraction (fraction of image in runs in 135 direction) from run length matrix-based features, and seven variables of sum average from coocurrence matrix-based features (SumAverg). The ideal cutoff value for predicting lymph node metastases was 270 for WavEnLH_s-2 (positive likelihood ratio 2.08). In addition, 135dr_LngREmph and 135dr_Fraction were correlated with the ratio of metastatic to examined lymph nodes.

Preoperative computed tomography high order texture features provide a useful imaging signature for the prediction of nodal involvement in pancreatic cancer.

• Computed tomography
• Computer-assisted image processing
• Metastases
• Pancreatic ductal adenocarcinoma
• Texture analysis

• Pancreatic adenocarcinoma
• Pancreatic resection
• Routine portal vein resection
• Surgical radicality
• True tumor infiltration

The impact of histopathologic tumor invasion of the superior mesenteric vein (SMV)/portal vein (PV) on prognosis in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreatectomy remains controversial. A meta-analysis was performed to assess this issue.

Eighteen observational studies comprising 5242 patients were eligible, of whom 2199 (41.9%) patients received SMV/PV resection. Histopathologic tumor invasion was detected in 1218 (58.1%) of the 2096 resected SMV/PV specimens. SMV/PV invasion was associated with higher rates of poor tumor differentiation (P = 0.002), lymph node metastasis (P < 0.001), perineural invasion (P < 0.001), positive resection margins (P = 0.004), and postoperative tumor recurrence (P < 0.001). SMV/PV invasion showed a significantly negative effect on survival in total patients who underwent pancreatectomy with and without SMV/PV resection (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.08–1.35; P = 0.001) and in patients who underwent pancreatectomy with SMV/PV resection (HR: 1.88, 95% CI, 1.48–2.39; P < 0.001).

A systematic literature search was performed to identify articles published from January 2000 to August 2016. Data were pooled for meta-analysis using Review Manager 5.3.

Histopathologic tumor invasion of the SMV/PV is associated with more aggressive biologic behavior and could be used as an indicator of poor prognosis after PDAC resection.

• pancreatic adenocarcinoma
• portal vein
• prognosis
• superior mesenteric vein
• survival

• Carcinoma
• Pancreas neoplasms
• Pancreatic ductal
• Pathology
• Surgical
• Survival

• enhanced recovery after surgery
• pancreatic cancer
• pancreaticoduodenectomy
• perioperative management

• China/epidemiology
• Comorbidity
• Female
• Humans
• Male
• Mortality
• Neoplasm Grading
• Neoplasm Staging
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/epidemiology
• Pancreatic Neoplasms/rehabilitation
• Pancreatic Neoplasms/surgery
• Pancreaticoduodenectomy/adverse effects
• Pancreaticoduodenectomy/methods
• Perioperative Care/methods
• Postoperative Complications
• Treatment Outcome

• Adult
• Aged
• Cohort Studies
• Databases, Factual
• Disease-Free Survival
• Female
• Humans
• Kaplan-Meier Estimate
• Logistic Models
• Lymph Node Excision/methods
• Lymph Node Excision/statistics & numerical data
• Lymph Nodes/pathology
• Lymph Nodes/surgery
• Male
• Middle Aged
• Neoplasm Invasiveness/pathology
• Neoplasm Staging
• Odds Ratio
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/surgery
• Pancreaticoduodenectomy/methods
• Pancreaticoduodenectomy/mortality
• Prognosis
• Proportional Hazards Models
• Retrospective Studies
• Risk Assessment
• Survival Analysis
• Treatment Outcome
• Young Adult
• Pancreatic Neoplasms

• Howard Hughes Medical Institute

• Neoadjuvant therapy
• Pancreatectomy
• Pancreatic ductal adenocarcinoma
• Pancreatoduodenectomy

• Adenocarcinoma/surgery
• Carcinoma, Pancreatic Ductal/drug therapy
• Carcinoma, Pancreatic Ductal/radiotherapy
• Carcinoma, Pancreatic Ductal/surgery
• Chemoradiotherapy
• Chemotherapy, Adjuvant
• Female
• Humans
• Male
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local/drug therapy
• Neoplasm Recurrence, Local/radiotherapy
• Neoplasm Recurrence, Local/surgery
• Pancreatic Neoplasms
• Pancreaticoduodenectomy
• Preoperative Care
• Retrospective Studies

Ephrin receptor A4 (EphA4) is overexpressed in human pancreatic adenocarcinoma (PDAC) and activate cell growth. Recent studies have identified small molecules that block EphA4. In this study, we investigated the correlation between EphA4 expression and the prognosis of patients with PDAC. We also examined the cytostatic efficacy of 2,5-dimethylpyrrolyl benzoic acid (compound 1), a small molecule that blocks EphA4, in PDAC cells. Overall survival of patients with EphA4 positivity was significantly shorter than that of patients with EphA4 negativity (P = 0.029). In addition, multivariate analysis revealed that EphA4 expression was an independent prognostic factor in PDAC patients (P = 0.039). Compound 1 showed a cytostatic efficacy in PDAC cells expressing EphA4 in vitro and in vivo. Our study indicated that compound 1 suppressed both EphA4 and Akt phosphorylations, and induced apoptosis in PDAC cells expressing EphA4. In conclusion,compound 1 has a high potential as a therapeutic agent for patients with PDAC.

• 2,5-dimethylpyrrolyl benzoic acid
• EphA4
• human pancreatic cancer
• orthotopic models
• prognostic factor

• CA19-9 antigen
• pancreatic adenocarcinoma
• pancreatic neoplasms
• predictor of mortality
• veteran

Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and insights into both disease etiology and targeted intervention are needed. A total of 109 micro-dissected PDA cases were subjected to whole-exome sequencing. Microdissection enriches tumour cellularity and enhances mutation calling. Here we show that environmental stress and alterations in DNA repair genes associate with distinct mutation spectra. Copy number alterations target multiple tumour suppressive/oncogenic loci; however, amplification of MYC is uniquely associated with poor outcome and adenosquamous subtype. We identify multiple novel mutated genes in PDA, with select genes harbouring prognostic significance. RBM10 mutations associate with longer survival in spite of histological features of aggressive disease. KRAS mutations are observed in >90% of cases, but codon Q61 alleles are selectively associated with improved survival. Oncogenic BRAF mutations are mutually exclusive with KRAS and define sensitivity to vemurafenib in PDA models. High-frequency alterations in Wnt signalling, chromatin remodelling, Hedgehog signalling, DNA repair and cell cycle processes are observed. Together, these data delineate new genetic diversity of PDA and provide insights into prognostic determinants and therapeutic targets.

Diagnosis of pancreatic ductal adenocarcinoma (PDA) has poor long-term survival rates with limited therapy options. Here Witkiewicz et al. use microdissection and whole-exome sequencing to identify novel recurrent PDA mutations, highlighting the genetic diversity of this aggressive cancer.

• Adenocarcinoma/mortality
• Adenocarcinoma/pathology
• Adenocarcinoma/surgery
• Adult
• Aged
• Aged, 80 and over
• Female
• Follow-Up Studies
• Humans
• Lymph Nodes/pathology
• Male
• Mesenteric Veins/pathology
• Mesenteric Veins/surgery
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Staging
• Pancreatectomy
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/surgery
• Portal Vein/pathology
• Portal Vein/surgery
• Postoperative Period
• Prognosis
• Prospective Studies
• Risk Factors
• Surveys and Questionnaires
• Survival Rate
• Pancreatic Neoplasms

AIM: To explore the morbidity and risk factors of postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy.

METHODS: The data from 196 consecutive patients who underwent pancreaticoduodenectomy, performed by different surgeons, in the General Hospital of the People’s Liberation Army between January 1^st, 2013 and December 31^st, 2013 were retrospectively collected for analysis. The diagnoses of POPF and clinically relevant (CR)-POPF following pancreaticoduodenectomy were judged strictly by the International Study Group on Pancreatic Fistula Definition. Univariate analysis was performed to analyze the following factors: patient age, sex, body mass index (BMI), hypertension, diabetes mellitus, serum CA19-9 level, history of jaundice, serum albumin level, blood loss volume, pancreatic duct diameter, pylorus preserving pancreaticoduodenectomy, pancreatic drainage and pancreaticojejunostomy. Multivariate logistic regression analysis was used to determine the main independent risk factors for POPF.

RESULTS: POPF occurred in 126 (64.3%) of the patients, and the incidence of CR-POPF was 32.7% (64/196). Patient characteristics of age, sex, BMI, hypertension, diabetes mellitus, serum CA19-9 level, history of jaundice, serum albumin level, blood loss volume, pylorus preserving pancreaticoduodenectomy and pancreaticojejunostomy showed no statistical difference related to the morbidity of POPF or CR-POPF. Pancreatic duct diameter was found to be significantly correlated with POPF rates by univariate analysis and multivariate regression analysis, with a pancreatic duct diameter ≤ 3 mm being an independent risk factor for POPF (OR = 0.291; P = 0.000) and CR-POPF (OR = 0.399; P = 0.004). The CR-POPF rate was higher in patients without external pancreatic stenting, which was found to be an independent risk factor for CR-POPF (OR = 0.394; P = 0.012). Among the entire patient series, there were three postoperative deaths, giving a total mortality rate of 1.5% (3/196), and the mortality associated with pancreatic fistula was 2.4% (3/126).

CONCLUSION: A pancreatic duct diameter ≤ 3 mm is an independent risk factor for POPF. External stent drainage of pancreatic secretion may reduce CR-POPF mortality and POPF severity.

• Pancreaticoduodenectomy
• Pancreatic fistula
• Complication
• Pancreatic duct

• Aged
• Chi-Square Distribution
• China
• Drainage/instrumentation
• Female
• Humans
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Pancreatic Ducts/pathology
• Pancreatic Ducts/surgery
• Pancreatic Fistula/diagnosis
• Pancreatic Fistula/etiology
• Pancreatic Fistula/mortality
• Pancreatic Fistula/prevention & control
• Pancreaticoduodenectomy/adverse effects
• Retrospective Studies
• Risk Factors
• Severity of Illness Index
• Stents
• Treatment Outcome

• Adenocarcinoma/genetics
• Carcinoma, Pancreatic Ductal/genetics
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genes, Neoplasm
• Humans
• Lymph Nodes/pathology
• Pancreatic Neoplasms/genetics
• Prognosis
• Reproducibility of Results
• Signal Transduction/genetics
• Survival Analysis
• Up-Regulation/genetics
• Pancreatic Neoplasms

• L30 CA124093 NCI NIH HHS
• P30 CA044579 NCI NIH HHS
• T32 CA009109 NCI NIH HHS

Introduction. Several histopathologic features of periampullary tumors have been shown to be correlated with prognosis. We evaluated their association with mortality at multiple time points. Methods. A retrospective chart review identified 207 patients with periampullary adenocarcinomas who underwent pancreaticoduodenectomy between January 1, 2001 and December 31, 2009. Clinicopathologic features were assessed, and the data were analyzed using univariate and multivariate methods. Results. In univariate analysis, perineural invasion had a strong association with 1-year mortality (OR 3.03, CI 1.42–6.47), and one lymph node (LN) increase in the LN ratio (LNR) equated with a 5-fold increase in mortality. In contrast, LN status (OR 6.42, CI 3.32–12.41) and perineural invasion (OR 5.44, CI 2.81–10.52) had the strongest associations with mortality at 3 years. Using Cox proportional hazards, perineural invasion (HR 2.61, CI 1.77–3.85) and LN status (HR 2.69, CI 1.84–3.95) had robust associations with overall mortality. Recursive partitioning analysis identified LNR as the most important risk factor for mortality at 1 and 3 years. Conclusions. Overall mortality was closely related to the LNR within the first year, while longer follow-up periods demonstrated a stronger association with perineural invasion and overall LN status. Therefore, the current staging for periampullary tumors may need to be updated to include the LNR.