Exploring a novel composite method using non-contrast EUS enhanced microvascular imaging and cyst fluid analysis to differentiate pancreatic cystic lesions.

BACKGROUND AND AIMS: Differentiating pancreatic cystic lesions (PCLs) remains a diagnostic challenge. The use of high-definition imaging modalities which detect tumor microvasculature have been described in solid lesions. We aim to evaluate the usefulness of cystic microvasculature when used in combination with cyst fluid biochemistry to differentiate PCLs. METHODS: We retrospectively analyzed 110 consecutive patients with PCLs from 2 Italian Hospitals who underwent EUS with H-Flow and EUS fine needle aspiration to obtain cystic fluid. The accuracy of fluid biomarkers was evaluated against morphological features on radiology and EUS. Gold standard for diagnosis was surgical resection. A clinical and radiological follow up was applied in those patients who were not resected because not surgical indication and no signs of malignancy were shown. RESULTS: Of 110 patients, 65 were diagnosed with a mucinous cyst, 41 with a non-mucinous cyst, and 4 with an undetermined cyst. Fluid analysis alone yielded 76.7% sensitivity, 56.7% specificity, 77.8 positive predictive value (PPV), 55.3 negative predictive value (NPV) and 56% accuracy in diagnosing pancreatic cysts alone. Our composite method yielded 97.3% sensitivity, 77.1% specificity, 90.1% PPV, 93.1% NPV, 73.2% accuracy. CONCLUSIONS: This new composite could be applied to the holistic approach of combining cyst morphology, vascularity, and fluid analysis alongside endoscopist expertise.

Resectability of Pancreatic Cancer Is in the Eye of the Observer: A Multicenter, Blinded, Prospective Assessment of Interobserver Agreement on NCCN Resectability Status Criteria.

Objectives: To determine the reproducibility of the National Comprehensive Cancer Network (NCCN) resectability status classification for pancreatic cancer. Background: The NCCN classification defines 3 resectability classes (resectable, borderline resectable, locally advanced), according to vascular invasion. It is used to recommend different approaches and stratify patients during clinical trials. Methods: Prospective, multicenter, observational study (trial ID: NCT03673423). Main outcome measure was the interobserver agreement of tumor assignment to different resectability classes and quantification of vascular invasion degrees. Agreement was measured by Fleiss' k (k = 1 perfect agreement; k = 0 agreement by chance). Sixty-nine computed tomography (CT) scans of pathologically confirmed pancreatic adenocarcinoma were independently reviewed in a blinded fashion by 22 observers from 11 hospitals (11 surgeons and 11 radiologists). Rating differences between surgeons or radiologists and between hospitals with different volumes (≥60 or <60 resections/year) were assessed. Results: Complete agreement among 22 observers was recorded in 5 CT scans (7.2%), whereas 25 CT scans (36.2%) were variously assigned to all 3 resectability classes. Interobserver agreement varied from fair to moderate (Fleiss' k range: 0.282-0.555), with the lowest agreement for borderline resectable tumors. Assessing vascular contact ≤180° had the lowest agreement for all vessels (k range: 0.196-0.362). The highest concordance was recorded for venous invasion >180° (k range: 0.619-0.756). Neither reviewers' specialty nor hospital volume influenced the agreement. Conclusions: There is high variability in the assignment to resectability categories, which may compromise the reliability of treatments recommendations and the evidence of trials stratifying patients in resectability classes. Criteria should be revised to allow a reproducible classification.

Nutritional support and therapy in pancreatic surgery: A position paper of the International Study Group on Pancreatic Surgery (ISGPS).

BACKGROUND: The optimal nutritional therapy in the field of pancreatic surgery is still debated. METHODS: An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group. RESULTS: The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery-related complications. In addition to patient's weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short-term and long-term outcomes. The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so-called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition. After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase-1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement. CONCLUSION: The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short- and long-term outcomes.

Role of preoperative biliary stents, bile contamination and antibiotic prophylaxis in surgical site infections after pancreaticoduodenectomy.

BACKGROUND: The routine use of preoperative biliary drainage before pancreaticoduodenectomy (PD) remains controversial. This observational retrospective study compared stented and non-stented patients undergoing PD to assess any differences in post-operative morbidity and mortality. METHODS: A total of 180 consecutive patients who underwent PD and had intra-operative bile cultures performed between January 2010 and February 2013 were retrospectively identified. All patients received peri-operative intravenous antibiotic prophylaxis, primarily cefazolin. RESULTS: Overall incidence of post-operative surgical complications was 52.3 %, with no difference between stented and non-stented patients (53.4 % vs. 51.1 %; p = 0.875). However, stented patients had a significantly higher incidence of deep incisional surgical site infections (SSIs) (p = 0.038). In multivariate analysis, biliary stenting was confirmed as a risk factor for deep incisional SSIs (p = 0.044). Significant associations were also observed for cardiac disease (p = 0.010) and BMI ≥25 kg/m(2) (p = 0.045). Enterococcus spp. were the most frequent bacterial isolates in bile (74.5 %) and in drain fluid (69.1 %). In antimicrobial susceptibilty testing, all Enterococci isolates were cefazolin-resistant. CONCLUSION: Given the increased risk of deep incisional SSIs, preoperative biliary stenting in patients underging PD should be used only in selected patients. In stented patients, an antibiotic with anti-enterococcal activity should be chosen for PD prophylaxis.

Adjuvant PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) or gemcitabine followed by chemoradiation in pancreatic cancer: a randomized phase II trial.

BACKGROUND: Information from randomized trials on the role of combination chemotherapy in the adjuvant treatment of pancreatic adenocarcinoma is limited. This randomized phase II trial aimed to identify the most promising regimen warranting phase III evaluation. METHODS: Therapy-naive patients, age 18-75 years, Karnofsky Performance Status (KPS)>60, gross total resection of stage IB-III pancreatic adenocarcinoma, stratified for center and surgical margins, were randomly assigned to receive either gemcitabine 1 g/m2 weekly on days 1, 8, and 15 (arm A) or the PEFG regimen (cisplatin and epirubicin 40 mg/m2, day 1; gemcitabine 600 mg/m2, days 1, 8; 5-fluorouracil 200 mg/m2 daily, days 1-28) (arm B). Chemotherapy was administered every 4 weeks for 3 months and followed by irradiation concurrent to continuous infusion of 5-fluorouracil 250 mg/m2 daily. Primary endpoint was the probability of being disease-free at 1 year from surgery. Assuming P0=35% and P1=55%, α=.05 and ß=.10, the study was to enroll 51 patients per arm. RESULTS: A total of 102 patients were randomized; 100 were eligible (arm A: 51; arm B: 49). Baseline characteristic (A/B) were: Median age was 61/60 years; 75% had KPS>80 75/76%; 36% grade 3 tumor 29/43%, 79% stage IIB/III 75/84%, 31% R1 resection 35/29%. Survival figures (A/B) were: Median disease-free survival was 11.7 and 15.2 months; 1-year disease-free survival 49.0% (95% confidence interval [95% CI] 35-63%) and 69.4% (95% CI 56-83%); median survival 24.8 and 28.9 months. Combination chemotherapy produced more hematological toxicity without relevant differences in nonhematological toxicities. CONCLUSIONS: The 4-drug regimen deserves further assessment in resectable pancreatic cancer.

Final results of a prospective trial of a PEFG (Cisplatin, Epirubicin, 5-Fluorouracil, Gemcitabine) regimen followed by radiotherapy after curative surgery for pancreatic adenocarcinoma.

BACKGROUND: Postoperative management of patients with pancreatic adenocarcinoma (PA) is controversial. METHODS: The aim of this pilot study was to assess the feasibility of postoperative combination chemotherapy followed by radiotherapy in patients aged 18-70 years with a histological diagnosis of PA, and Karnofsky performance status (KPS) > or =70. Cisplatin and epirubicin 40 mg/m2 on day 1, gemcitabine 600 mg/m2 on day 1 and 8, and 5-fluorouracil 200 mg/m2/day as protracted infusion (PEFG regimen) were delivered every 28 days for 4 cycles. Assuming a minimum one-year disease-free survival (DFS) of interest of 65% and a maximum of low interest of 45% (alpha 0.05; beta 0.10), the target enrollment was 51 patients, and the strategy would be considered to deserve further analysis if more than 29 patients were DF at one-year from surgery. RESULTS: Fifty-one patients, KPS >80: 29, median tumor size 3.5 cm, stage II/III/IVA: 2/34/13, grade 3-4: 22, positive resection margins: 26, node positive: 46, received 179 cycles of chemotherapy. Main grade 3/4 toxicity consisted of neutropenia (51%), thrombocytopenia (18%), and anemia (4%). One-year DFS was 67 +/- 7%. Two-year overall survival was 53 +/- 7%. CONCLUSION: Postoperative management of PA with this multimodality strategy was well tolerated and yielded a promising outcome.