Prognostic value of major pathological response following neoadjuvant therapy for non resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of this study is to evaluate the impact of major pathological response on overall survival (OS) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma following neoadjuvant treatment, and to identify predictors of major pathological response. METHODS: Patients surgically resected following neoadjuvant treatment between 2010 and 2020 at the Pederzoli Hospital were retrospectively analyzed. Pathologic response was assessed using the College of American Pathologists (CAP) score, and major pathological response was defined as CAP 0-1. OS was estimated and compared using the Kaplan-Meier method and log-rank test. A logistic and Cox regression model were performed to identify predictors of major pathologic response and OS. RESULTS: Overall, 200 patients were included in the study. A major and complete pathological response were observed in 52(26.0%) and 15(7.3%) patients respectively. The 1-, 3-, 5-year OS was 92.7, 67.2, and 41.7%, and 71.0, 37.4, and 20.8% in patients with or without major pathologic response respectively (log-rank test p < 0.001). Major pathologic response was confirmed as independent predictor of OS (OR 0.50 95%CI 0.29-0.88, p = 0.01). Post-treatment CA19-9 normalization (OR 4.20 95%CI 1.14-10.35, p = 0.02) and radiological post-treatment tumor residual size<25 mm (OR 2.71 95%CI 1.27-5.79, p = 0.01) were found to be independent predictors of major pathologic response. CONCLUSION: Patients experienced a major pathological response after neoadjuvant treatment have an increased survival, and major pathologic response is an independent predictor of OS. A normal CA19-9 value and radiological tumor size at restaging are confirmed to be independent predictors of major pathologic response.

Prognostic Factors After Pancreatectomy for Pancreatic Cancer Initially Metastatic to the Liver.

BACKGROUND: Resection of initially oligometastatic pancreatic ductal adenocarcinoma (PDAC) following response to first-line chemotherapy is controversial. We herein updated a previous case series to investigate the oncologic outcomes and preoperative factors that could drive the decision-making process. METHODS: This retrospective analysis was limited to patients with liver-only synchronous metastases who experienced complete regression of the metastatic component and underwent pancreatectomy between October 2008 and July 2020 at two high-volume institutions. Clinical-pathologic variables were captured, and inflammation-based prognostic scores were calculated. Recurrence and survival analyses were performed using standard statistical methods. RESULTS: Overall, 52 patients were included. FOLFIRINOX was the most employed chemotherapy regimen (63.5%). Post-treatment tumor size, serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were significantly decreased relative to baseline evaluation. The median time from diagnosis to pancreatectomy was 10.2 months, while the median time from chemotherapy completion to pancreatectomy was 2 months. Major postoperative complications occurred in 26.9% of patients, while postoperative mortality was nil. The median disease-free survival (DFS) and overall survival (OS) from pancreatectomy were 16.5 and 23.0 months, respectively, and the median OS from diagnosis was 37.2 months. At multivariable analysis, vascular resection, operative time, prognostic nutrition index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were associated with OS. Operative time, platelet × neutrophil/lymphocyte count (SII), and PNI were associated with DFS. CONCLUSIONS: We confirm promising outcomes of selected patients who underwent pancreatectomy following downstaging of liver metastases. The absence of vascular involvement of the primary tumor, good nutritional status, and low inflammatory index scores could be useful to select candidates for resection.

Role of next-generation genomic sequencing in targeted agents repositioning for pancreaticoduodenal cancer patients.

BACKGROUND: Pancreaticoduodenal cancer (PDC) is a group of malignant tumors arising in the ampullary region, which lack approved targeted therapies for their treatment. METHODS: This retrospective, observational study is based on Secondary Data Use (SDU) previously collected during a multicenter collaboration, which were subsequently entered into a predefined database and analyzed. FoundationOne CDx or Liquid, a next-generation DNA sequencing (NGS) service, was used to identify genomic alterations of patients who failed standard treatments. Detected alterations were described according to ESMO Scale of Clinical Actionability for molecular Targets (ESCAT). RESULTS: NGS analysis was performed in 68 patients affected by PDC. At least one alteration ranking tier I, II, III, or IV according to ESCAT classification was detected in 8, 1, 9, and 12 patients respectively (44.1%). Ten of them (33.3%) received a matched therapy. Patients with ESCAT tier I to IV were generally younger than the overall population (median = 54, range = 26-71 years), had an EGOG performance status score = 0 (83.3%), and an uncommon histological or clinical presentation. The most common mutations with clinical evidence of actionability (ESCAT tier I-III) involved genes of the RAF (10.3%), BRCA (5.9%) or FGFR pathways (5.9%). We present the activity of the RAF kinases inhibitor sorafenib in patients with RAF-mutated advanced PDC. CONCLUSIONS: In advanced PDC, NGS is a feasible and valuable method for enabling precision oncology. This genomic profiling method might be considered after standard treatments failure, especially in young patients maintaining a good performance status, in order to detect potentially actionable mutations and offer molecularly targeted therapeutic approaches.

Decoding Grade B Pancreatic Fistula: A Clinical and Economical Analysis and Subclassification Proposal.

OBJECTIVE: The aim of this study was to describe characteristics and management approaches for grade B pancreatic fistula (B-POPF) and investigate whether it segregates into distinct subclasses. BACKGROUND: The 2016 ISGPS refined definition of B-POPF is predicated on various postoperative management approaches, ranging from prolonged drainage to interventional procedures, but the spectrum of clinical severity within this entity is yet undefined. METHODS: Pancreatectomies performed at 2 institutions from 2007 to 2016 were reviewed to identify B-POPFs and their treatment strategies. Subclassification of B-POPFs into 3 classes was modeled after the Fistula Accordion Severity Grading System (B1: prolonged drainage only; B2: pharmacologic management; B3: interventional procedures). Clinical and economic outcomes, unique from the ISGPS definition qualifiers, were analyzed across subclasses. RESULTS: B-POPF developed in 320 of 1949 patients (16.4%), and commonly required antibiotics (70.3%), prolonged drainage (67.8%), and enteral/parenteral nutrition (54.7%). Percutaneous drainage occurred in 79 patients (24.7%), always in combination with other strategies. Management of B-POPFs was widely heterogeneous with a median of 2 approaches/patient (range 1 to 6) and 38 various strategy combinations used. Subclasses B1-3 comprised 19.1%, 52.2%, and 28.8% of B-POPFs, respectively, and were associated with progressively worse clinical and economic outcomes. These results were confirmed by multivariable analysis adjusted for clinical and operative factors. Notably, distribution of the B-POPF subclasses was influenced by institution and type of resection (P < 0.001), while clinical/demographic predictors proved elusive. CONCLUSION: B-POPF is a heterogeneous entity, where 3 distinct subclasses with increasing clinical and economic burden can be identified. This classification framework has potential implications for accurate reporting, comparative research, and performance evaluation.

Risk Factors and Mitigation Strategies for Pancreatic Fistula After Distal Pancreatectomy: Analysis of 2026 Resections From the International, Multi-institutional Distal Pancreatectomy Study Group.

OBJECTIVE: To identify a clinical fistula risk score following distal pancreatectomy. BACKGROUND: Clinically relevant pancreatic fistula (CR-POPF) following distal pancreatectomy (DP) is a dominant contributor to procedural morbidity, yet risk factors attributable to CR-POPF and effective practices to reduce its occurrence remain elusive. METHODS: This multinational, retrospective study of 2026 DPs involved 52 surgeons at 10 institutions (2001-2016). CR-POPFs were defined by 2016 International Study Group criteria, and risk models generated using stepwise logistic regression analysis were evaluated by c-statistic. Mitigation strategies were assessed by regression modeling while controlling for identified risk factors and treating institution. RESULTS: CR-POPF occurred following 306 (15.1%) DPs. Risk factors independently associated with CR-POPF included: age (<60 yrs: OR 1.42, 95% CI 1.05-1.82), obesity (OR 1.54, 95% CI 1.19-2.12), hypoalbuminenia (OR 1.63, 95% CI 1.06-2.51), the absence of epidural anesthesia (OR 1.59, 95% CI 1.17-2.16), neuroendocrine or nonmalignant pathology (OR 1.56, 95% CI 1.18-2.06), concomitant splenectomy (OR 1.99, 95% CI 1.25-3.17), and vascular resection (OR 2.29, 95% CI 1.25-3.17). After adjusting for inherent risk between cases by multivariable regression, the following were not independently associated with CR-POPF: method of transection, suture ligation of the pancreatic duct, staple size, the use of staple line reinforcement, tissue patches, biologic sealants, or prophylactic octreotide. Intraoperative drainage was associated with a greater fistula rate (OR 2.09, 95% CI 1.51-3.78) but reduced fistula severity (P < 0.001). CONCLUSIONS: From this large analysis of pancreatic fistula following DP, CR-POPF occurrence cannot be reliably predicted. Opportunities for developing a risk score model are limited for performing risk-adjusted analyses of mitigation strategies and surgeon performance.

Identification of an Optimal Cut-off for Drain Fluid Amylase on Postoperative Day 1 for Predicting Clinically Relevant Fistula After Distal Pancreatectomy: A Multi-institutional Analysis and External Validation.

OBJECTIVE: The aim of this study was to investigate the relationship between drain fluid amylase value on the first postoperative day (DFA1) and clinically relevant fistula (CR-POPF) after distal pancreatectomy (DP), and to identify the cut-off of DFA1 that optimizes CR-POPF prediction. BACKGROUND: DFA1 is a well-recognized predictor of CR-POPF after pancreatoduodenectomy, but its role in DP is largely unexplored. METHODS: DFA1 levels were correlated with CR-POPF in 2 independent multi-institutional sets of DP patients: developmental (n = 338; years 2012 to 2017) and validation cohort (n = 166; years 2006 to 2016). Cut-off choice was based on Youden index calculation, and its ability to predict CR-POPF occurrence was tested in a multivariable regression model adjusted for clinical, demographic, operative, and pathological variables. RESULTS: In the developmental set, median DFA1 was 1745 U/L and the CR-POPF rate was 21.9%. DFA1 correlated with CR-POPF with an area under the curve of 0.737 (P < 0.001). A DFA1 of 2000 U/L had the highest Youden index, with 74.3% sensitivity and 62.1% specificity. Patients in the validation cohort displayed different demographic and operative characteristics, lower values of DFA1 (784.5 U/L, P < 0.001), and reduced CR-POPF rate (10.2%, P < 0.001). However, a DFA1 of 2000 U/L had the highest Youden index in this cohort as well, with 64.7% sensitivity and 75.8% specificity. At multivariable analysis, DFA1 ≥2000 U/L was the only factor significantly associated with CR-POPF in both cohorts. CONCLUSION: A DFA1 of 2000 U/L optimizes CR-POPF prediction after DP. These results provide the substrate to define best practices and improve outcomes for patients receiving DP.

Clinical Implications of the 2016 International Study Group on Pancreatic Surgery Definition and Grading of Postoperative Pancreatic Fistula on 775 Consecutive Pancreatic Resections.

OBJECTIVE: The aim of the present study was to evaluate the clinical implications of the 2016 International Study Group for Pancreatic Surgery (ISGPS) definition and classification of postoperative pancreatic fistula (POPF) using a single high-volume institutional cohort of patients undergone pancreatic surgery. BACKGROUND: The ISGPS definition and grading system of POPF has been recently updated. Although the rationale for the changes was supported by previous studies, the effect of the new definition and classification scheme on surgical series has not been established. METHODS: A total of 775 patients undergone pancreatic surgery in our institute from 2013 to 2015 were reviewed. The parameters modified in the ISGPS classification were analyzed according to postoperative outcomes. Finally the classification was validated by external clinical and economical outcomes. RESULTS: Applying the 2016 scheme, 17.5% of patients changed classification group compared to the 2015 system. Grade B increased from 11.5% to 22.1%, whereas grade C decreased from 15.2% to 4.6%. Biochemical leak occurred in 7% of patients, and it did not differ from the non-POPF condition in terms of surgical outcomes. Non-POPF group, grades B and C POPF differed significantly in terms of intensive care unit staying (P < 0.001), length of stay (P < 0.001), readmission rate (P < 0.001), and hospital costs (P < 0.001). CONCLUSIONS: The present study has confirmed the pertinence of the changes introduced in the 2016 ISGPS POPF definition and grading. This updated classification is effective in identifying three conditions that differ in terms of clinical and economic outcomes. These results suggested the reliability of the new definition and scheme in classifying POPF-related outcomes.

Prevent Pancreatic Fistula after Pancreatoduodenectomy: Possible Role of Ultrasound Elastography.

BACKGROUND: The purpose of the study is to evaluate the utility of acoustic radiation force impulse (ARFI) on pancreatic tissue as a preoperative predictor of postoperative pancreatic fistula (POPF). Studied patients underwent exclusively to pancreaticoduodenectomy (PD) surgery. METHODS: Shear wave velocity of pancreas was measured using ARFI in 71 patients scheduled for PD. An intraoperative pancreas palpation was made by surgeons. A postoperative clinical evaluation to detect occurrence of POPF was performed. Sensitivity, specificity, positive and negative predictive values together with the accuracy of the method were investigated. RESULTS: Incidence of fistula observed in 17 patients with soft pancreas was approximately 53% vs. 47% without fistula. Percentage of patients without fistula was higher (66%) among 24 patients with medium parenchymal texture values, and was even higher (69%) in 26 patients with hard pancreas. Comparing ARFI and intraoperative pancreatic palpation, low wave velocity values (≤1.40 m/s) match 60% with soft parenchyma assessed by palpation and high values (>2 m/s) match 59% with hard pancreas on palpation. CONCLUSIONS: This study shows that ARFI elastography may be clinically useful as a preoperative predictor of pancreatic fistula following PD.

Polyester sutures for pancreaticojejunostomy protect against postoperative pancreatic fistula: a case-control, risk-adjusted analysis.

BACKGROUND: There is wide variability in the use of suture material for pancreatic anastomosis after pancreaticoduodenectomy (PD). This study evaluates the role of suture material on clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticojejunostomy (PJ) in a risk-adjusted setting. METHODS: A retrospective study comparing (polyester) PE with polydioxanone (PDO) in 520 PDs. Patients were matched for risk for CR-POPF according to the fistula risk score (FRS) with the propensity score. RESULTS: The matched PE and PDO groups consisted of 232 patients. The incidence of CR-POPF was lower for PE group (11.6 vs. 22%, p<0.01), with a lower rate of grade B (10.3 vs. 15.5%, p<0.01) and C (1.3 vs. 6.5%, p<0.01). After stratifying by fistula risk zone, PE suture remained associated with a reduced incidence of CR-POPF (9.4 vs. 15.6% low-, p = 0.04; 15.6 vs. 28.1% intermediate-, p = 0.02; 16.7 vs. 83.3% high-risk zone, p<0.01, respectively). Multivariable analysis demonstrated that pancreatic texture, preoperative diagnosis, FRS and the use of PE sutures were independent predictors of CR-POPF. CONCLUSIONS: In the setting of a case-control matched for risk analysis, the use of PE suture for PJ is associated with a significant reduction of CR-POPF.

Multicenter, Prospective Trial of Selective Drain Management for Pancreatoduodenectomy Using Risk Stratification.

OBJECTIVE: This multicenter study sought to prospectively evaluate a drain management protocol for pancreatoduodenectomy (PD). BACKGROUND: Recent evidence suggests value for both selective drain placement and early drain removal for PD. Both strategies have been associated with reduced rates of clinically relevant pancreatic fistula (CR-POPF)-the most common and morbid complication after PD. METHODS: The protocol was applied to 260 consecutive PDs performed at two institutions over 17 months. Risk for ISGPF CR-POPF was determined intraoperatively using the Fistula Risk Score (FRS); drains were omitted in negligible/low risk patients and drain fluid amylase (DFA) was measured on postoperative day 1 (POD 1) for moderate/high risk patients. Drains were removed early (POD 3) in patients with POD 1 DFA ≤5,000 U/L, whereas patients with POD 1 DFA >5,000 U/L were managed by clinical discretion. Outcomes were compared with a historical cohort (N = 557; 2011-2014). RESULTS: Fistula risk did not differ between cohorts (median FRS: 4 vs 4; P = 0.933). No CR-POPFs developed in the 70 (26.9%) negligible/low risk patients. Overall CR-POPF rates were significantly lower after protocol implementation (11.2 vs 20.6%, P = 0.001). The protocol cohort also demonstrated lower rates of severe complication, any complication, reoperation, and percutaneous drainage (all P < 0.05). These patients also experienced reduced hospital stay (median: 8 days vs 9 days, P = 0.001). There were no differences between cohorts in the frequency of bile or chyle leaks. CONCLUSIONS: Drains can be safely omitted for one-quarter of PDs. Drain amylase analysis identifies which moderate/high risk patients benefit from early drain removal. This data-driven, risk-stratified approach significantly decreases the occurrence of clinically relevant pancreatic fistula.

Incorporation of Procedure-specific Risk Into the ACS-NSQIP Surgical Risk Calculator Improves the Prediction of Morbidity and Mortality After Pancreatoduodenectomy.

OBJECTIVE: This multicenter study sought to evaluate the accuracy of the American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) surgical risk calculator for predicting outcomes after pancreatoduodenectomy (PD) and to determine whether incorporating other factors improves its predictive capacity. BACKGROUND: The ACS-NSQIP surgical risk calculator has been proposed as a decision-support tool to predict complication risk after various operations. Although it considers 21 preoperative factors, it does not include procedure-specific variables, which have demonstrated a strong predictive capacity for the most common and morbid complication after PD - clinically relevant pancreatic fistula (CR-POPF). The validated Fistula Risk Score (FRS) intraoperatively predicts the occurrence of CR-POPF and serious complications after PD. METHODS: This study of 1480 PDs involved 47 surgeons at 17 high-volume institutions. Patient complication risk was calculated using both the universal calculator and a procedure-specific model that incorporated the FRS and surgeon/institutional factors. The performance of each model was compared using the c-statistic and Brier score. RESULTS: The FRS was significantly associated with 30-day mortality, 90-day mortality, serious complications, and reoperation (all P < 0.0001). The procedure-specific model outperformed the universal calculator for 30-day mortality (c-statistic: 0.79 vs 0.68; Brier score: 0.020 vs 0.021), 90-day mortality, serious complications, and reoperation. Neither surgeon experience nor institutional volume significantly predicted mortality; however, surgeons with a career PD volume >450 were less likely to have serious complications (P < 0.001) or perform reoperations (P < 0.001). CONCLUSIONS: Procedure-specific complication risk influences outcomes after pancreatoduodenectomy; therefore, risk adjustment for performance assessment and comparative research should consider these preoperative and intraoperative factors along with conventional ACS-NSQIP preoperative variables.

Quantitative Assessment of Pancreatic Texture Using a Durometer: A New Tool to Predict the Risk of Developing a Postoperative Fistula.

BACKGROUND: Pancreatic texture is one of the key predictors of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). Currently, the "gold standard" for assessment of pancreatic texture is surgeon's subjective evaluation through manual palpation. AIM: To evaluate a new "durometer" that is able to assess quantitatively the pancreatic stiffness by measuring its elastic module (i.e., the resistance offered by the pancreatic stump when elastically deformed expressed in mPa). METHODS: Measurements were obtained from the pancreatic remnant during 138 consecutive PDs performed at the Department of General and Pancreatic Surgery-The Pancreas Institute, University of Verona Hospital Trust. Values were correlated to clinical features and, in particular, with the senior surgeon's evaluation of pancreatic texture (hard/soft). Sixteen beating-heart donors were used as a control group to assess the stiffness of a non-pathologic pancreas. Univariate analysis was performed for the assessment of POPF predictors. RESULTS: Durometry allowed segregating between non-pathologic, soft and hard pancreas according to surgeon's evaluation (mean values 111 vs. 196 vs. 366 mPa, p < 0.01). There were no significant differences in stiffness with regard to histology, BMI, and neoadjuvant therapy. Larger tumors (>20 mm) and male sex were associated with greater stiffness on univariate analysis. Pancreatic texture, pancreatic duct size, BMI, prior neoadjuvant therapy, and histology were predictors of POPF. Patients who developed POPF showed a lesser stiffness (178 vs. 261 mPa, p = 0.05). CONCLUSION: Assessment of pancreatic stiffness using a durometer correlated with the surgeon's evaluation of pancreatic texture. Measurement of pancreatic parenchymal stiffness is reliable and correlates with the development of POPF.

Pancreaticojejunostomy after pancreaticoduodenectomy: Suture material and incidence of post-operative pancreatic fistula.

PURPOSE: Pancreatic fistula represents the most important complication in terms of clinical management and costs after pancreaticoduodenectomy. A lot of studies have investigated several techniques in order to reduce pancreatic fistula, but data on the effect of sutures material on pancreatic fistula are not available. The analysis investigated the role of suture material in influencing pancreatic fistula rate and severity. METHODS: Results from 130 consecutive pancreaticoduodenectomy with pancreaticojejunostomy performed between March 2013 and September 2014 were prospectively collected and analyzed. In 65 cases pancreaticojejunostomy was performed with absorbable sutures, in the other 65 cases using non-absorbable sutures (polyester, silk and polybutester). RESULTS: Pancreaticojejunostomy with non-absorbable sutures had the same incidence of pancreatic fistula, but less severe and with less episodes of post-operative bleeding if compared with absorbable sutures. A sub-analysis was carried out comparing polydioxanone with polyester: the latter was associated with a lower pancreatic fistula rate (11.9% vs. 31.7%; p = 0,01) and less severe pancreatic anastomosis dehiscence (grade C - 0% vs. 30%; p = 0.05). Univariate and multivariate analysis confirmed that hard pancreatic texture, pancreatic ductal adenocarcinoma at final histology and the use of polyester for pancreaticojejunostomy were associated with a lower pancreatic fistula rate (p < 0.05). CONCLUSION: Further studies are needed to investigate the effects of pancreatic juice and bile on different sutures and pancreatic tissue response to different materials. However, pancreaticojejunostomy performed with polyester sutures is safe and feasible and is associated to a lower incidence of pancreatic fistula with less severe clinical impact.

Pancreaticoduodenectomy for distal cholangiocarcinoma: surgical results, prognostic factors, and long-term follow-up.

PURPOSE: Prognostic indicators for distal cholangiocarcinoma have not been widely confirmed because of its rarity. Despite the early appearance of symptoms, it has a very poor prognosis. The aim of this study was to identify prognostic factors in patients undergoing pancreaticoduodenectomy (PD) for distal bile duct cancer (DBDC) in a high-volume center for pancreatic disease. METHODS: From January 2000 to December 2013, 1490 PD were performed for periampullary disease. Data from all patients with histologically proven cholangiocarcinoma were reviewed. Preoperative data, post-operative complications, pathologic features, and survival were investigated. RESULTS: Among 50 histologically proven DBDC (3.3 %), 4 patients who underwent CBD resection were excluded. Thus, the study population consisted of 46 patients. Overall surgical morbidity rate was 67.4 %; mortality was nil. Major complications were pancreatic fistula (47.8 %), abdominal collections (34.8 %), post-pancreatectomy hemorrhage (21.7 %), and delayed gastric emptying (10.9 %). The majority of resections were R0 (73.9 %). The presence of metastatic lymph nodes (N1) was identified in 76.1 % of cases. Among N1 cases, the most frequently involved lymph nodes were pancreaticoduodenal nodes (50 %), hepatoduodenal ligament nodes (21.7 %), superior mesenteric artery nodes (8.7 %), and anterior hepatic artery nodes (4.3 %). Overall, survival rates were 88.8, 40, and 18 % at 1, 3, and 5 years, respectively. Median survival was 31 months. By univariate analysis, only tumor grading and nodal metastasis were predictors of poor prognosis (p < 0.05). These findings were not confirmed in multivariate analysis. CONCLUSIONS: This study shows that DBDC is a rare entity even if large surgical series are reviewed. Tumor differentiation and nodal status have been confirmed as important prognostic factors. Pancreaticoduodenectomy remains the procedure of choice in order to obtain free surgical margins and in order to harvest the correct number of lymph nodes for a correct staging.

Role of Adjuvant Multimodality Therapy After Curative-Intent Resection of Ampullary Carcinoma.

Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, Setting, and Participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main Outcomes and Measures: Overall survival. Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41). Conclusions and Relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined.

Local Ablative Strategies for Ductal Pancreatic Cancer (Radiofrequency Ablation, Irreversible Electroporation): A Review.

Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis. Locally advanced pancreatic cancer (LAPC) accounts for the 40% of the new diagnoses. Current treatment options are based on chemo- and radiotherapy regimens. Local ablative techniques seem to be the future therapeutic option for stage-III patients with PDAC. Radiofrequency Ablation (RFA) and Irreversible Electroporation (IRE) are actually the most emerging local ablative techniques used on LAPC. Initial clinical studies on the use of these techniques have already demonstrated encouraging results in terms of safety and feasibility. Unfortunately, few studies on their efficacy are currently available. Even though some reports on the overall survival are encouraging, randomized studies are still required to corroborate these findings. This study provides an up-to-date overview and a thematic summary of the current available evidence on the application of RFA and IRE on PDAC, together with a comparison of the two procedures.

Cystic Neoplasm of the Pancreas.

Cystic neoplasms of the pancreas (CNPs) are not considered as rare entities any more. Imaging-based population studies attested an overall prevalence of 2 %, but that becomes five times higher on individuals of more than 70 year old. This family of neoplasms includes a wide spectrum of benign, borderline, and malignant lesions whose actual biological behavior has not been completely clarified yet. Moreover, the management of CNPs still represents a challenge for gastrointestinal (GI) specialists. While many CNPs have an indolent behavior that justifies surveillance, others should be resected because of the risk of progression to invasive cancer. Due to the high morbidity related to pancreatic resections, the surgeon should balance very carefully the advantages of a radical resection with the risks of an unrequested dangerous procedure. We reviewed the current issues regarding CNPs, with a particular focus on the clinical and radiological features that are integrated in the current guidelines and that drive the management of these patients.