REDISCOVER guidelines for borderline-resectable and locally advanced pancreatic cancer: management algorithm, unanswered questions, and future perspectives.

The REDISCOVER guidelines present 34 recommendations for the selection and perioperative care of borderline-resectable (BR-PDAC) and locally advanced ductal adenocarcinoma of the pancreas (LA-PDAC). These guidelines represent a significant shift from previous approaches, prioritizing tumor biology over anatomical features as the primary indication for resection. Condensed herein, they provide a practical management algorithm for clinical practice. However, the guidelines also highlight the need to redefine LA-PDAC to align with modern treatment strategies and to solve some contradictions within the current definition, such as grouping "difficult" and "impossible" to resect tumors together. Furthermore, the REDISCOVER guidelines highlight several areas requiring urgent research. These include the resection of the superior mesenteric artery, the management strategies for patients with LA-PDAC who are fit for surgery but unable to receive multi-agent neoadjuvant chemotherapy, the approach to patients with LA-PDAC who are fit for surgery but demonstrate high serum Ca 19.9 levels even after neoadjuvant treatment, and the optimal timing and number of chemotherapy cycles prior to surgery. Additionally, the role of primary chemoradiotherapy versus chemotherapy alone in LA-PDAC, the timing of surgical resection post-neoadjuvant/primary chemoradiotherapy, the efficacy of ablation therapies, and the management of oligometastasis in patients with LA-PDAC warrant investigation. Given the limited evidence for many issues, refining existing management strategies is imperative. The establishment of the REDISCOVER registry ( https://rediscover.unipi.it/ ) offers promise of a unified research platform to advance understanding and improve the management of BR-PDAC and LA-PDAC.

Very Early Recurrence After Curative Resection for Pancreatic Ductal Adenocarcinoma: Proof of Concept for a "Biological R2 Definition".

PURPOSE: Very early recurrence after radical surgery for pancreatic ductal adenocarcinoma (PDAC) has been poorly investigated. This study was designed to evaluate this group of patients who developed recurrence, within 12 weeks after surgery, defined as "biological R2 resections (bR2)." METHODS: Data from patients who underwent surgical resection as upfront procedure or after neoadjuvant treatment for PDAC between 2015 and 2019 were analyzed. Disease-free, disease-specific survival, and independent predictors of early recurrence were examined. The same analysis was performed separately for upfront and neoadjuvant treated patients. RESULTS: Of the 573 patients included in the study, 63 (11%) were classified as bR2. The rate of neoadjuvant treatment was similar in bR2 and in the remaining patients (44 vs. 42%, p = 0.78). After a median follow-up of 27 months, median DFS and DSS for the entire cohort were 17 and 43 months, respectively. Median DSS of bR2 group was 13 months. The only preoperative identifiable independent predictor of very early recurrence was body-tail site lesion, whereas all other were pathological: higher pT (8th classification), G3 differentiation, and high lymph node ratio. These predictors were confirmed for patients undergoing upfront surgery, whereas in the neoadjuvant group the only independent predictor was pT. CONCLUSIONS: One of ten patients with "radical" resected PDAC relapses very early after surgery (bR2); hence, imaging must be routinely repeated within 12 weeks. Despite higher biological aggressiveness and worse pathology, this bR2 cluster eludes our preoperative examinations.

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validate guidelines on the perioperative care of patients with borderline resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to non-surgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive mean to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR- and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Analysis of the Mechanical Characteristics of Human Pancreas through Indentation: Preliminary In Vitro Results on Surgical Samples.

Pancreatic surgery is extremely challenging and demands an extended learning curve to be executed with a low incidence of post-operative complications. The soft consistency of the human pancreas poses a primary challenge for pancreatic surgeons. This study aimed to analyze the preliminary mechanical characteristics of the human pancreas to develop a realistic synthetic phantom for surgical simulations in the near future. Pancreatic specimens, comprehensive of the pancreatic parenchyma and main pancreatic duct, were collected during pancreatic resections and analyzed through nano-bio-indentation (BioindenterTM UNHT3 Bio, Anton Paar GmbH, Graz, Austria) to measure the elastic modulus. Comparisons were made between slow and fast loading rates, immediate and post-freezing analyses, and multipoint indentations. The results demonstrated that a slow loading rate (30 µN/min), immediate analysis, and multipoint measurements are crucial for obtaining accurate values of the elastic modulus of the human pancreas (1.40 ± 0.47 kPa). In particular, the study revealed that analysis after freezing could impact the outcomes of the indentation. Moreover, the study suggested that both the pancreatic parenchyma and the main pancreatic duct should be analyzed to achieve a more precise and comprehensive definition of the. mechanical features of the pancreas. These preliminary findings represent the initial steps toward defining the consistency and mechanical characteristics of human pancreatic tissue with the goal of creating a realistic synthetic phantom.

Minimally invasive versus open radical antegrade modular pancreatosplenectomy for pancreatic ductal adenocarcinoma: an entropy balancing analysis.

BACKGROUND: The safety and efficacy of minimally invasive radical antegrade modular pancreatosplenectomy (MI-RAMPS) remain to be established in pancreatic cancer (PDAC) METHODS: Eighty-five open (O)-RAMPS were compared to 93 MI-RAMPS. The entropy balance matching approach was used to compare the two cohorts, eliminating the selection bias. Three models were created. Model 1 made O-RAMPS equal to the MI-RAMPS cohort (i.e., compared the two procedures for resectable PDAC); model 2 made MI-RAMPS equal to O-RAMPS (i.e., compared the two procedures for borderline-resectable PDAC); model 3, compared robotic and laparoscopic RAMPS. RESULTS: O-RAMPS and MI-RAMPS showed "non-small" differences for BMI, comorbidity, back pain, tumor size, vascular resection, anterior or posterior RAMPS, multi-visceral resection, stump management, grading, and neoadjuvant therapy. Before reweighting, O-RAMPS had fewer clinically relevant postoperative pancreatic fistulae (CR-POPF) (20.0% vs. 40.9%; p = 0.003), while MI-RAMPS had a higher mean of lymph nodes (25.7 vs. 31.7; p = 0.011). In model 1, MI-RAMPS and O-RAMPS achieved similar results. In model 2, O-RAMPS was associated with lower comprehensive complication index scores (MD = 11.2; p = 0.038), and CR-POPF rates (OR = 0.2; p = 0.001). In model 3, robotic-RAMPS had a higher probability of negative resection margins. CONCLUSION: In patients with anatomically resectable PDAC, MI-RAMPS is feasible and as safe as O-RAMPS.

The Choice of the Most Appropriate Suture Threads for Pancreatic Anastomoses on the Basis of Their Mechanical Characteristics.

The choice of the most appropriate suture threads for pancreatic anastomoses may play an important role in reducing the incidence of post-operative pancreatic fistula (POPF). The literature on this topic is still not conclusive. The aim of this study was to analyze the mechanical characteristics of suture materials to find the best suture threads for pancreatic anastomoses. A single-axial electromagnetic actuation machine was used to obtain the stress-deformation relationship curves and to measure both the ultimate tensile strength (UTS) and the Young's modulus at the 0-3% deformation range (E0-3) of four different suture materials (Poliglecaprone 25, Polydioxanone, Polyglactin 910, and Polypropylene) at baseline and after incubation in saline solution, bile, and pancreatic juice for 1, 3, and 7 days. Polydioxanone and Polypropylene showed stable values of UTS and E0-3 in all conditions. Polyglactin 910 presented significant UTS and E0-3 variations between different time intervals in all types of liquids analyzed. Poliglecaprone 25 lost half of its strength in all biological liquids analyzed but maintained low E0-3 values, which could reduce the risk of lacerations of soft tissues. These results suggest that Polydioxanone and Poliglecaprone 25 could be the best suture materials to use for pancreatic anastomoses. In vivo experiments will be organized to obtain further confirmations of this in vitro evidence.

Early Recurrence after Upfront Surgery for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor, due to early recurrence (ER) of the disease. A global definition of ER is lacking and different cut-off values (6, 8, and 12 months) have been adopted. The aims of this study were to define the optimal cut-off for the definition of ER and predictive factors for ER. METHODS: Recurrence was recorded for all consecutive patients undergoing upfront surgery for PDAC at our institute between 2010 and 2017. Receiver operating characteristic (ROC) curves were utilized, to estimate the optimal cut-off for the definition of ER as a predictive factor for poor post-progression survival (PPS). To identify predictive factors of ER, univariable and multivariable logistic regression models were used. RESULTS: Three hundred and fifty one cases were retrospectively evaluated. The recurrence rate was 76.9%. ER rates were 29.0%, 37.6%, and 47.6%, when adopting 6, 8, and 12 months as cut-offs, respectively. A significant difference in median PPS was only shown between ER and late recurrence using 12 months as cut-off (p = 0.005). In the multivariate analysis, a pre-operative value of CA 19-9 > 70.5 UI/L (OR 3.10 (1.41-6.81); p = 0.005) and the omission of adjuvant treatment (OR 0.18 (0.08-0.41); p < 0.001) were significant predictive factors of ER. CONCLUSIONS: A twelve-months cut-off should be adopted for the definition of ER. Almost 50% of upfront-resected patients presented ER, and it significantly affected the prognosis. A high preoperative value of CA 19-9 and the omission of adjuvant treatment were the only predictive factors for ER.

Hemorrhoid laser dearterialization: systematic review and meta-analysis.

Hemorrhoidal disease is a common and troublesome condition. Excisional hemorrhoidectomy can assure the best chance of cure but it is hampered by postoperative pain and potential long-term morbidity therefore minimally invasive techniques have been developed. Since 2009 a doppler-guided hemorrhoidal dearterialization with laser (the hemorrhoidal laser procedure; HeLP) has been proposed to control symptoms without significant sequelae. The aim of this systematic review is to analyze the benefits and disadvantages of HeLP for symptomatic hemorrhoids. The Medline/PubMed, Embase, and Cochrane library databases were searched from January 2010 to March 2022, language was restricted to English and documents to the full text. Randomized and non-randomized, prospective and retrospective cohort studies were included. Risk of bias assessment was performed using the Risk of bias for non-randomized studies (ROBINS-I) and the RoB2 Tool for randomized clinical trial. Primary outcome was to assess the efficacy of HeLP on symptoms' resolution. Secondary objectives were postoperative pain and complications, comparison with other interventional techniques, and evaluation of long-term recurrence. Whenever possible, a meta-analysis was conducted. The GRADE approach was employed to assess the certainty of evidence. We included six non-randomized and one randomized study. HeLP improved or resolved preoperative symptoms in 83.6 to 100% of patients during follow-up. In the randomized study symptoms resolved in 90% of patients after HeLP and 53.3% after rubber band ligation as comparator. Published data indicate that HeLP is effective, relatively safe, with limited recurrence rate, after a short to medium follow-up. The quality of evidence was however low. There is a paucity of studies assessing the benefits or harms of laser dearterialization for the treatment of hemorrhoids and randomized trials are furthermore rare, therefore trials with adequate power and proper design, assessing the advantages and disadvantages of HeLP versus other minimally invasive techniques, are needed. Furthermore, studies evaluating long-term follow-up are wanted.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

Long-Term Survivors after Upfront Resection for Pancreatic Ductal Adenocarcinoma: An Actual 5-Year Analysis of Disease-Specific and Post-Recurrence Survival.

BACKGROUND: Data on long-term actual survival in patients with surgically resected pancreatic ductal adenocarcinoma (PDAC) are limited. The aim of this study was to evaluate the actual 5-year disease-specific survival (DSS) and post-recurrence survival (PRS) in patients who underwent pancreatectomy for PDAC. METHODS: Data from patients who underwent upfront surgical resection for PDAC between 2009 and 2014 were analyzed. Exclusion criteria included PDAC arising in the background of an intraductal papillary mucinous neoplasm and patients undergoing neoadjuvant therapy. All alive patients had a minimum follow-up of 60 months. Independent predictors of PRS, DSS, and survival > 5 years were searched. RESULTS: Of the 176 patients included in this study, 48 (27%) were alive at 5 years, but only 20 (11%) had no recurrence. Median PRS was 12 months. In the 154 patients after disease recurrence, independent predictors of shorter PRS were total pancreatectomy, G3 tumors, early recurrence (< 12 months from surgery), and no treatment at recurrence. Median DSS was 36 months. Independent predictors of DSS were CA19-9 at diagnosis > 200 U/mL, total pancreatectomy, N + status, G3 tumors and perineural invasion. Only the absence of perineural invasion was a favorable independent predictor of survival > 5 years. CONCLUSION: More than one-quarter of patients who underwent upfront surgery for PDAC were alive after 5 years, although only 11% of the initial cohort were cancer-free. Long-term survival can also be achieved in tumors with more favorable biology in an upfront setting followed by adjuvant chemotherapy.

Recurrence after surgical resection of pancreatic cancer: the importance of postoperative complications beyond tumor biology.

BACKGROUND: Current treatment of potentially resectable pancreatic ductal adenocarcinoma (PDAC) includes pancreatic resection followed by adjuvant therapy. Aim of this study is to identify factors that are related with overall and early recurrence after pancreatectomy for PDAC. METHODS: Retrospective analysis of patients with histologically confirmed PDAC who underwent pancreatectomy between September 2009 and December 2014. Early relapse was defined as recurrence within 12 months after surgery. Univariate/multivariate analysis was performed to identify prognostic factors for recurrence. RESULTS: 261 patients were included (54% males, mean age 67 years). Neoadjuvant and adjuvant treatments were performed in 55 (21%) and 243 (93%) patients. Overall morbidity was 56% with a rate of grade 3-4 Clavien-Dindo complications of 25%. Median disease-free survival was 18 months. Multivariate analysis identified nodal metastases (OR: 3.6) and perineural invasion (OR: 2.14) as independent predictors of disease recurrence in the entire cohort. 76 patients (29%) had an early recurrence. Poorly differentiated tumors (OR: 3.019) and grade 3-4 Clavien-Dindo complications (OR: 3.05) were independent risk factors for early recurrence. CONCLUSION: Although overall recurrence is associated with tumor-related factors, severe postoperative complications represent an independent predictor of early recurrence. Patients at increased risk of severe postoperative complications may benefit from neoadjuvant therapy.

R Status is a Relevant Prognostic Factor for Recurrence and Survival After Pancreatic Head Resection for Ductal Adenocarcinoma.

BACKGROUND: The prognostic role of resection margins in pancreatic ductal adenocarcinoma (PDAC) is debated. This study aimed to investigate the impact that global and individual resection margin status after pancreatic head resection for PDAC has on disease-free survival (DFS) and disease-specific survival (DSS). METHODS: Surgical specimens of pancreaticoduodenectomy/total pancreatectomy performed for PDAC were examined with a standardized protocol. Surgical margin status (biliary, pancreatic neck, duodenal, anterior and posterior pancreatic, superior mesenteric vein groove and superior mesenteric artery margins) was classified as the presence of malignant cells (1) directly at the inked surface (R1 direct), (2) within less than 1 mm (R1 ≤ 1 mm), or (3) with a distance greater than 1 mm (R0). Patients with a positive neck margin at the final histology were excluded from the study. RESULTS: Of the 362 patients included in the study, 179 patients (49.4 %) had an R0 resection, 123 patients (34 %) had an R1 ≤ 1 mm resection, and 60 patients (16.6 %) had an R1 direct resection. The independent predictors of DFS were R1 direct resection (hazard ratio [HR], 1.49), R1 ≤ 1 mm resection (HR, 1.38), involvement of one margin (HR, 1.36), and involvement of two margins or more (HR, 1.55). When surgical margins were analyzed separately, only R1 ≤ 1 mm superior mesenteric vein margin (HR, 1.58) and R1 direct posterior margin (HR, 1.69) were independently associated with DFS. CONCLUSIONS: Positive R status is an independent predictor of DFS (R1 direct and R1 ≤ 1 mm definitions) and of DSS (R1 direct). The presence of multiple positive margins is a risk factor for cancer recurrence and poor survival. Different surgical margins could have different prognostic roles.

Liver transplantation from brain-dead donors on mechanical circulatory support: a systematic review of the literature.

Mechanical circulatory support (MCS) refers to a range of rescue devices to assist circulation for the treatment of heart failure, including venoarterial extracorporeal membrane oxygenation (VA-ECMO) and ventricular assist devices (VADs). This review aims at evaluating the transplant outcome of the livers procured from brain-dead donors on MCS, who are currently considered as having extended criteria. We identified 22 records (17 on VA-ECMO and 5 on VADs), most of which (68.2%) were case reports. We performed a meta-analysis only when the outcome was reported homogeneously among studies; otherwise, we illustrated the results with narrative synthesis. A total of 156 liver transplants (LTs) have been reported, where VA-ECMO was initiated in the donor with resuscitative intent or as a bridge to donation. Early graft survival approached 100% in most studies. The pooled rate of primary nonfunction was 1% (95% CI: 0-3%). Only three successful LTs from VAD donors have been reported. Particular attention should be paid to cardiological history, biochemical tests, and imaging, as well as MCS parameters, to determine graft eligibility for transplantation. Although further analysis is needed in this field, the results of this review advocate a more systematic consideration of brain-dead patients on MCS as potential liver donors.

Vascular resection during pancreatectomy for pancreatic head cancer: A technical issue or a prognostic sign?

BACKGROUND: There is an increased interest in venous vascular resection associated with pancreatic resection for pancreatic ductal adenocarcinoma as an upfront procedure or after neoadjuvant treatment. The aim of this study was to evaluate the impact of venous vascular resection for pancreatic ductal adenocarcinoma on postoperative and long-term outcomes. METHODS: The study is a retrospective analysis of patients who underwent pancreatectomy for pancreatic head pancreatic ductal adenocarcinoma with and without venous vascular resection between January 2010 and April 2018. The impact of venous vascular resection on postoperative and pathologic data was analyzed. Univariate and multivariate analyses of predictors of disease-free and disease-specific survival were analyzed for the entire cohort. A propensity-score matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. RESULTS: Four hundred and eighty-one patients were included, and 126 (26%) underwent a venous vascular resection. Patients undergoing venous vascular resection had higher morbidity (64% vs 54%; P = .026) with no differences in 90-day postoperative mortality (3.1 vs 2.8%; P = .5). Venous vascular resections were also significantly associated with R1 resections (52% vs 37%; P = .002) and perineural invasion (87% vs 77%; P = .017). Five-year disease-free survival in patients with and without venous vascular resection were 7% and 20% (P = .018), respectively. Independent predictors of worse disease-free survival included venous vascular resection, positive lymph node status, and perineural invasion. Independent predictors of worse disease-specific survival were perineural invasion and positive nodal status, while adjuvant treatment was a protective factor. Five-year disease-specific survival in patients with and without venous vascular resection were 19% and 35% (P = .42). CONCLUSION: Pancreatectomy with venous vascular resection can be accomplished safely. Venous vascular resections are associated with poor prognostic factors and with a worse clinical outcome, being a significant predictor of cancer recurrence.

Chemopreventive Agents After Pancreatic Resection for Ductal Adenocarcinoma: Legend or Scientific Evidence?

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related death in the USA. A wealth of evidence has demonstrated the chemopreventive activity of aspirin, statins, and metformin against PDAC. The aim of this study is to investigate the effect of aspirin, statins, and metformin on disease-free survival (DFS) and disease-specific survival (DSS) in a large population of PDAC patients undergoing pancreatic resection. PATIENTS AND METHODS: All patients who underwent pancreatic resections between January 2015 and September 2018 were retrospectively reviewed. The potentially "chemopreventive agents" considered for the analysis were aspirin, statins, and metformin. Drug use was defined in case of regular assumption at least 6 months before diagnosis and regularly after surgery along the follow-up period. RESULTS: A total of 430 patients were enrolled in this study, with median DFS and DSS of 21 months (IQR 13-30) months and 34 (IQR 26-52) months, respectively. On multivariable analysis, use of aspirin was associated with better DFS (HR: 0.62; p = 0.038). Metformin was associated with better DFS, without reaching statistical significance (p = 0.083). Use of statins did not influence DFS in the studied population. Aspirin, metformin, and statins were not associated with better DSS on multivariable analysis. Factors influencing DSS were pT3/pT4, N1, N2, no adjuvant treatment, G3, and ASA score > 3. CONCLUSIONS: The results suggest that chronic use of aspirin is associated with increased DFS but not with better DSS after surgical resection in patients with PDAC.

Positive neck margin at frozen section analysis is a significant predictor of tumour recurrence and poor survival after pancreatodudenectomy for pancreatic cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Postoperative Outcomes and Functional Recovery After Preoperative Combination Chemotherapy for Pancreatic Cancer: A Propensity Score-Matched Study.

Introduction: Previous studies show encouraging oncologic outcomes for neoadjuvant chemotherapy (NACT) in the setting of pancreatic ductal adenocarcinoma (PDAC). However, recent literature reported an increased clinical burden in patients undergoing pancreaticoduodenectomy (PD) following NACT. Therefore, the aim of our study was to assess the impact of NACT on postoperative outcomes and recovery after PD. Methods: A retrospective propensity score-matched study was performed including all patients who underwent PD for PDAC in a single center between 2015 and 2018. Patients treated with NACT for resectable, borderline resectable or locally advanced PDAC were matched based on nearest neighbor propensity scores in a 1:1 ratio to patients who underwent upfront resection. Propensity scores were calculated using 7 perioperative variables, including gender, age, BMI, ASA score, Charlson-Deyo comorbidity score, fistula risk score (FRS), vascular resection. Primary outcome was the number and severity of complications at 90-days after surgery measured by the comprehensive complication index (CCI). Data are reported as median (IQR) or number of patients (%). Results: Of 283 resected patients, 95 (34%) were treated with NACT. Before matching, NACT patients were younger, had less comorbidities (Charlson-Deyo score 0 vs. 1, p = 0.04), similar FRS [2 (0-3) for both groups], and more vascular resections performed [n = 28 (30%) vs. n = 26 (14%), p < 0.01]. After propensity-score matching, preoperative and intraoperative characteristics were comparable. Postoperatively, CCI was similar between groups [8.7 (0-29.6) for both groups, p = 0.59]. NACT patients had a non-statistically significant increase in superficial incisional surgical site infections [n = 12 (13%) vs. 6 (6%), p = 0.14], while no difference was found for overall infectious complications and organ-space SSI. The occurrence of clinically-relevant pancreatic fistula was similar between groups [10 (11%) vs. 13 (14%), p = 0.51]. No difference was found between groups for length of hospital stay [8 (7-15) vs. 8 (7-14) days, p = 0.62], and functional recovery outcomes. Conclusion: After propensity score adjustment for perioperative risk factors, NACT did not worsen postoperative outcomes and functional recovery following PD for PDAC compared to upfront resection.

Local Excision of a Mucinous Adenocarcinoma of the Anal Margin (Extramammary Paget's Disease) and Reconstruction with a Bilateral V-Y Flap.

The case of a 75-year-old female with invasive extramammary Paget's disease of the anal margin, without involvement of the anal canal, is reported. The patient underwent wide local excision of the lesion with reconstruction with a double V-Y flap, a biopsy of the inguinal sentinel node, and a laparoscopic temporary colostomy. No guidelines exist on the treatment of this rare disease, and both wide local excision and abdominoperineal resection have been proposed. In the present case, the absence of invasion of the anal canal, also confirmed by intraoperative biopsies on the resection margins, and of local lymph node metastasis, as confirmed by the sentinel lymph node biopsy, allowed a sphincter-sparing operation with good functional and oncological results.

Ki-67 prognostic and therapeutic decision driven marker for pancreatic neuroendocrine neoplasms (PNENs): A systematic review.

BACKGROUND: We systematically evaluate the current evidence regarding Ki-67 as a prognostic factor in pancreatic neuroendocrine neoplasms to evaluate the differences of this marker in primary tumors and in distant metastases as well as the values of Ki-67 obtained by fine needle aspiration and by histology. METHODS: The literature search was carried out using the MEDLINE/PubMed database, and only papers published in the last 10 years were selected. RESULTS: The pancreatic tissue suitable for Ki-67 evaluation was obtained from surgical specimens in the majority of the studies. There was a concordance of 83% between preoperative and postoperative Ki-67 evaluation. Pooling the data of the studies which compared the Ki-67 values obtained in both cytological and surgical specimens, we found that they were not related. The assessment of Ki-67 was manual in the majority of the papers considered for this review. In order to eliminate manual counting, several imaging methods have been developed but none of them are routinely used at present. Twenty-two studies also explored the role of Ki-67 utilized as a prognostic marker for pancreatic neuroendocrine neoplasms and the majority of them showed that Ki-67 is a good prognostic marker of disease progression. Three studies explored the Ki-67 value in metastatic sites and one study demonstrated that, in metachronous and synchronous liver metastases, there was no significant variation in the index of proliferation. CONCLUSIONS: Ki-67 is a reliable prognostic marker for pancreatic neuroendocrine neoplasms.