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Objective: To assess the probability of being cured of pancreatic ductal adenocarcinoma (PDAC) by pancreatic surgery. Background: Statistical cure implies that a patient treated for a specific disease will have the same life expectancy as if he/she never had that disease. Methods: Patients who underwent pancreatic resection for PDAC between 2010 and 2021 were retrospectively identified using a multiinstitutional database. A nonmixture statistical cure model was applied to compare disease-free survival to the survival expected for a matched general population. Results: Among 2554 patients, either in the setting of upfront (n=1691) or neoadjuvant strategy (n=863), the cure model showed that the probability that surgery would offer the same life expectancy (and tumor-free) as the matched general populationwas 20.4% (95%CI: 18.3, 22.5). Cure likelihood reached the 95%of certainty (time to cure) after 5.3 years (95% CI: 4.7, 6.0). Apreoperative model was developed based on tumor stage at diagnosis (P=0.001), radiologic size (P=0.001), response to chemotherapy (P=0.007), American Society of Anesthesiology class (P=0.001), and preoperative Ca19-9 (P=0.001). A postoperative model with the addition of surgery type (P=0.015), pathologic size (P=0.001), tumor grading (P=0.001), resection margin (P=0.001), positive lymph node ratio (P=0.001), and the receipt of adjuvant therapy (P=0.001) was also developed. Conclusions: Patients operated for PDAC can achieve a life expectancy similar to that of the general population, and the likelihood of cure increases with the passage of recurrence-free time. An online calculator was developed and available at https://aicep.website/?cff-form=15. [ABSTRACT FROM AUTHOR]

Objective: To describe PNI and to evaluate its impact on disease-free (DFS) and overall survival (OS) in patients with resected pancreatic ductal adenocarcinoma (PDAC). Summary of Background Data: Although PNI is a prognostic factor for survival in many GI cancers, there is limited knowledge regarding its impact on tumor recurrence, especially in "early stage disease" (PDAC ≤20 mm, R0/ N0 PDAC). Methods: This multicenter retrospective study included patients undergoing PDAC resection between 2009 and 2014. The association of PNI with DFS and OS was analyzed using Cox proportional-hazards models. Results: PNI was found in 87% of 778 patients included in the study, with lower rates in PDAC ≤20 mm (78.7%) and in R0/N0 tumors (70.6%). PNI rate did not differ between patients who underwent neoadjuvant therapy and upfront surgery (88% vs 84%, P = 0.08). Although not significant at multivariate analysis (P = 0.07), patients with PNI had worse DFS at univariate analysis (median DFS: 20 vs 15 months, P < 0.01). PNI was the only independent predictor of DFS in R0/N0 tumors (hazard ratio [HR]: 2.2) and in PDAC ≤ 20 mm (HR: 1.8). PNI was an independent predictor of OS in the entire cohort (27 vs 50 months, P = 0.01), together with G3 tumors, pN1 status, carbohydrate antigen (CA) 19.9 >37 and pain. Conclusions: PNI represents a major determinant of tumor recurrence and patients' survival in pancreatic cancer. The role of PNI is particularly relevant in early stages, supporting the hypothesis that invasion of nerves by cancer cells has a driving role in pancreatic cancer progression. [ABSTRACT FROM AUTHOR]

The oncological benefit of achieving a negative pancreatic neck margin through re-resection after a positive frozen section (FS) is debated. Aim of this network meta-analysis is to evaluate the survival benefit of re-resection after intraoperative FS neck margin examination following pancreatectomy for ductal adenocarcinoma. A systematic search of studies comparing different strategies for the management of positive FS was performed. Patients were classified in three groups based on FS and permanent section (PS): Group A (FS-, P S-R0), Group B (FS+, P S-R0), Group C (FS±, P S-R1). A frequent random-effects network-meta-analysis was made reporting the surface under the cumulative ranking (SUCRA). Primary endpoint was overall survival (OS). Secondary endpoints were pathological outcomes. Seven retrospectives studies with 4205 patients were included and 99.1% of the pancreatic resections were pancreatoduodenectomies. Group A had the highest probability of better OS (SUCRA = 90%), compared to Group B (SUCRA = 48.7%) and Group C, which was the worst prognostic scenario (SUCRA = 11.3%). Group B had still a probability of longer OS compared to Group C (SUCRA = 48.7% vs 11.3%). Pathological features were more favourable in Group A, with the highest SUCRA for T1-T2 tumors (92.6%), N0 status (89.4%), absence of perineural invasion (92.3%). Heterogeneity was low (τ-value <0.1) for OS, and moderate (τ-values: 0.1–0.6) for pT, pN, and perineural invasion. In conclusion, negative neck margin after primary resection (FS negative) or re-resection of a positive FS was associated with improved survival compared with P S-R1. However, any intraoperative positive FS can be considered as a prognostic factor associated with a more aggressive disease. [ABSTRACT FROM AUTHOR]

The possible benefit of frozen section (FS) analysis during (PD) for pancreatic ductal adenocarcinoma (PDAC) and of additional resection up to total pancreatectomy (TP) is debated. Aim of this work is to evaluate the prognostic role of positive FS analysis after PD for PDAC. Multicentric retrospective analysis on prospective databases of three institutions. Based on FS analysis patients were classified as FS negative/FS positive. All positive FS patients underwent extended PD (EPD) or TP. Postoperative outcomes, disease-free (DFS) and disease-specific survival (DSS) were evaluated. Of 371 patients, 58 (16%) had positive FS. This resulted in 313 (84%) SPD (standard pancreatoduodenectomy), 22 (6%) EPD and 36 (10%) TP. Postoperative mortality was higher in patients undergoing TP (11% compared to 4.5% in EPD and 1% in SPD; p = 0.01). 26% of patients underwent neoadjuvant therapy, and it did not decrease the rate of positive FS. Systemic/local relapse rates were 59% and 41% in negative FS group, and 78% and 22% in positive FS group (p = 0.031). Median DFS and DSS were 20 and 37 months in negative FS group, and 12 and 23 months in positive FS patients (p = 0.001). Independent predictors of recurrence were G3, N1/N2 status and positive FS. R1 resection, G3, N1/N2 status, perineural invasion and positive FS were independent predictors of DSS. Positive FS analysis is a poor prognostic factor after PD for PDAC. It is significantly associated with a high rate of R1 resection at final histology, PDAC recurrence and poor survival. [ABSTRACT FROM AUTHOR]

Previous studies on statins' effect on survival of patients with pancreatic ductal adenocarcinoma (PDAC) report conflicting results. To evaluate the association between statin use and PDAC patients' survival. A systematic review and meta-analysis was performed including case-control, cohort studies and randomized controlled trials assessing the association between statin use and survival in PDAC patients. Pooled HRs with 95%CIs were calculated using random effects model; publication bias was assessed through Begg and Mazumdar test and heterogeneity by I2 value. 14 studies with 33,137 PDAC patients, 40% under statins, were included. Statins use was associated to a reduced death risk (HR 0.871; 95%CI: 0.819; 0.927; p = 0.0001) suggesting a protective effect, homogeneous for different geographic areas. This effect was significant in surgically resected patients (HR 0.50; 95%CI: 0.32; 0.76; p = 0.001) but not in those with advanced disease (HR 0.78; 95%CI: 0.59; 1.02; p = 0.07). In studies providing information on statin type, only rosuvastatin resulted associated to a reduced risk of death (HR 0.88; 95%CI: 0.81; 0.96; p = 0.004). Statins use is significantly associated with a reduced risk of death in resected PDAC patients. This finding has to be considered with caution due to publication bias and the availability of only few studies for sensitivity analyses. [ABSTRACT FROM AUTHOR]

To assess the impact of delay from diagnosis to curative surgery on survival in patients with non-metastatic colon cancer. National Cancer database (NCDB) analysis (2004–2013) including all consecutive patients diagnosed with stage I-III colon cancer and treated with primary elective curative surgery. Short and long delays were defined as lower and upper quartiles of time from diagnosis to treatment, respectively. Age-, sex-, race-, tumor stage and location-, adjuvant treatment-, comorbidity- and socioeconomic factors-adjusted overall survival (OS) was compared between the two groups (short vs. long delay). A multivariable Cox regression model was used to identify the independent impact of each factor on OS. Time to treatment was <16 days in the short delay group (31,171 patients) and ≥37 days in the long delay group (29,617 patients). OS was 75.4 vs. 71.9% at 5 years and 56.6 vs. 49.7% at 10 years in short and long delay groups, respectively (both p < 0.0001). Besides demographic (comorbidities, advanced age) and pathological factors (transverse and right-vs. left-sided location, advanced tumor stage, poor differentiation, positive microscopic margins), treatment delay had a significant impact on OS (HR 1.06, 95% CI 1.05–1.07 per 14 day-delay) upon multivariable analysis. The adjusted hazard ratio for death increased continuously with delay times of longer than 30 days, to become significant after a delay of 40 days. This analysis using a national cancer database revealed a significant impact on OS when surgeries for resectable colon cancer were delayed beyond 40 days from time of diagnosis. [ABSTRACT FROM AUTHOR]

It remains unclear whether preoperative body composition may affect the prognosis of pancreatic cancer patients undergoing surgery. The aim of the present study was to assess the extent to which preoperative body composition impacts on postoperative complication severity and survival in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). A retrospective cohort study was performed on consecutive patients who underwent pancreatoduodenectomy with preoperative CT scan imaging available. Body composition parameters including total abdominal muscle area (TAMA), visceral fat area (VFA), subcutaneous fat area and liver steatosis (LS) were assessed. Sarcopenic obesity was defined as a high VFA/TAMA ratio. Postoperative complication burden was evaluated with the comprehensive complication index (CCI). Overall, 371 patients were included in the study. At 90 days after surgery, 80 patients (22%) experienced severe complications. The median CCI was 20.9 (IQR 0–30). At multivariate linear regression analysis, preoperative biliary drainage, ASA score ≥3, fistula risk score and sarcopenic obesity (37% increase; 95%CI 0.06–0.74; p = 0.046) were associated to an increase in CCI. Patient characteristics associated to sarcopenic obesity were older age, male gender and preoperative LS. At a median follow-up of 25 months (IQR 18–49), median disease-free survival (DFS) was 19 months (IQR 15–22). At cox-regression analysis, only pathological features were associated with DFS, while LS and other body composition measures did not show any prognostic role. The combination of sarcopenia and visceral obesity was significantly associated with increased complication severity after pancreatoduodenectomy for cancer. Patients' body composition did not affect disease free survival after pancreatic cancer surgery. [ABSTRACT FROM AUTHOR]

Background Identification of factors associated with dismal survival after surgery in resectable pancreatic ductal adenocarcinoma is important to select patients for neoadjuvant treatment. The present meta-analysis aimed to compare the results of distal pancreatectomy for resectable adenocarcinoma of the pancreatic body-tail with and without splenic vessels infiltration. Methods A systematic search was performed of PubMed, Embase and the Cochrane Library in accordance with PRISMA guidelines. The inclusion criteria were studies including patients who underwent distal pancreatectomy for pancreatic cancer with or without splenic vessels infiltration. 5-year overall survival (OS) was the primary outcomes. Meta-analysis was carried out applying time-to-event method. Results Six articles with 423 patients were analysed. Patients with pathological splenic artery invasion had a worse survival compared with those without infiltration (Hazard ratio 1.76, 95% CI 1.36–2.28; P < 0.0001). A similar results was found when considering pathological splenic vessels infiltration, showing that survival was significantly poorer when splenic vein infiltration was present (Hazard ratio 1.51, 95% CI 1.19–1.93; P = 0.0009). Conclusions This meta-analysis showed worse survival for patients with splenic vessels infiltration undergoing distal pancreatectomy for pancreatic cancer. Splenic vessels infiltration represents the stigmata of a more aggressive disease, although resectable. [ABSTRACT FROM AUTHOR]

Background (18)fluoro-deoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) might be a useful tool in the management of pancreatic ductal adenocarcinoma (PDAC). Aims The aim of this study was to analyze maximum standard uptake value (SUVmax) after 18FDG-PET/CT as predictor of survival outcomes and method to determine treatment strategies. Methods A consecutive series of patients who underwent preoperative 18FDG-PET/CT and subsequent resection for PDAC were retrospectively reviewed. Patients who underwent neoadjuvant chemotherapy were excluded. Results 46 patients were included in the analysis. Median follow-up was 27 months (4–67). Patients who recurred within 12 months showed a significantly higher preoperative median SUVmax (8.1 vs 6.1, p = 0.039). Receiver operating characteristics (ROC) curves for disease-free survival (DFS) and disease-specific survival (DSS) identified SUVmax of 6.0 as optimal cut-off. Multivariate analysis showed that SUVmax ≥ 6.0 was an independent predictor of poor DFS (HR 2.288, p = 0.024) and DSS (HR 4.875, p < 0.001). The combination of SUVmax ≥6.0 with CA19.9 ≥200 U/ml was significantly associated with survival outcomes in comparison to patients without concordantly elevated values. Conclusion SUVmax ≥6.0 is an independent predictor of DFS and DSS in resected PDAC. 18FDG-PET/CT might be considered in the preoperative evaluation of patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background This study aimed to develop and validate a preoperative prognostic model for death within one year post-surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC). Methods A derivation cohort study of 296 patients who underwent surgical resection of PDAC was prospectively enrolled in an observational study. Preoperative predictors of one year mortality were used to develop a risk score which was then validated in an external cohort of 182 patients with resectable PDAC. Results Seventy-eight out of 296 patients (26%) died within the first year. Preoperative independent predictors of one year mortality were: nutritional status (Geriatric Nutritional Risk Index, OR 2.23, 1.14–4.38; p = 0.02), American Society of Anaesthesiologists’ score (OR 2.56, 1.1–5.98; p = 0.03), abdominal or back pain at presentation (OR 2.51, 1.05–5.9; p = 0.038) and non metastatic liver disease as comorbidity (OR 4.5, 1.05–19.3; p = 0.043). A score ranging from 0 to 7 points was developed. In the validation cohort, the model was able to predict early mortality (OR 7.1, 3.9–12.7; p < 0.0001), with a predictive ability of 53.5% (Nagelkerke R 2 ), an area under the receiver operating characteristic curve of 88.7% and an acceptable calibration (goodness-of-fit test, p = 0.403). Conclusions Our new simple risk score proved reliable in forecasting one year mortality in patients with resectable PDAC. [ABSTRACT FROM AUTHOR]

Background New chemotherapeutic regimens have improved survival for stage IV pancreatic ductal adenocarcinoma and occasionally major response of liver metastases can be observed. Aim of this work is to analyze the outcomes of patients undergoing primary chemotherapy for liver metastases from pancreatic cancer and to evaluate the results of surgical resection. Methods Retrospective analysis. Exclusion criteria: patients with extra-hepatic metastases, patients with Eastern Cooperative Oncology Group performance status ≥3, patients undergoing supportive care alone. Results 127 patients were identified. Liver metastases were unilobar in 28.5% of patients. Chemotherapy regimens included gemcitabine alone or in association with other agents (44%), oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX 8%), and cisplatin, gemcitabine plus capecitabine and epirubicin (PEXG) or capecitabine and docetaxel (PDXG) or epirubicin and fluorouracil (PEFG) (48%). 56 patients (44%) had a complete (7%) or partial response (37%). surgical resection was carried out in 11 patients (8.5%). Median overall survival was 11 months for the entire cohort and 15 months for those with partial/complete response. In this sub-group median survival was significantly longer (46 versus 11 months) for patients undergoing resection (P < 0.0001). Independent predictors of overall survival were chemotherapy with multiple agents (HR: 0.512), surgical resection (HR: 0.360), >5 liver metastases at diagnosis (HR: 3.515), and CA 19.9 reduction < 50% of baseline value (HR: 2.708). Conclusions Surgical resection of primary pancreatic tumor with or without residual liver disease can be considered in selected cases after primary chemotherapy and it is associated with improved survival. [ABSTRACT FROM AUTHOR]

Purpose: The biological behavior and clinical outcome of renal cell carcinoma are difficult to predict. We investigated the prognostic impact of clinicopathological variables to establish a risk stratification model to predict recurrence and survival rates. Materials and Methods: We studied 230 patients with renal cell carcinoma (stages T1–4 Nx M0) who underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 48 months (range 3 to 140). Univariate and multivariate analyses were performed, and the influence of clinical presentation, histological tumor size, tumor grade, lymph node involvement and microvascular tumor invasion on disease-free and cancer specific survival curves was determined. A composition model based on independent prognostic variables was then created to stratify tumors into low, intermediate and high risk of progression. Results: The tumor recurrence rate was 17% (39 of 230) and the cancer specific mortality rate was 13% (31 of 230). Multivariate analyses determined that microvascular tumor invasion, tumor grade and tumor size were the only independent prognostic factors. Disease-free survival rates for low, intermediate and high risk tumors were 94.7%, 56.8% and 13.1%, respectively. Cancer specific survival rates were 94.7%, 61.7% and 32.0%, respectively. Conclusions: Tumor size, Fuhrman grade and microvascular tumor invasion are strong and independent predictors of survival of patients with renal cell carcinoma. Risk assessment and stratification based on this triad of pathological features may allow better individualization of followup schedules and trials of adjuvant treatment for patients with renal cell carcinoma. [Copyright &y& Elsevier]