Prospective minimally invasive pancreatic resections from the IGOMIPS registry: a snapshot of daily practice in Italy on 1191 between 2019 and 2022.

This retrospective analysis of the prospective IGOMIPS registry reports on 1191 minimally invasive pancreatic resections (MIPR) performed in Italy between 2019 and 2022, including 668 distal pancreatectomies (DP) (55.7%), 435 pancreatoduodenectomies (PD) (36.3%), 44 total pancreatectomies (3.7%), 36 tumor enucleations (3.0%), and 8 central pancreatectomies (0.7%). Spleen-preserving DP was performed in 109 patients (16.3%). Overall incidence of severe complications (Clavien-Dindo ≥ 3) was 17.6% with a 90-day mortality of 1.9%. This registry analysis provided some important information. First, robotic assistance was preferred for all MIPR but DP with splenectomy. Second, robotic assistance reduced conversion to open surgery and blood loss in comparison to laparoscopy. Robotic PD was also associated with lower incidence of severe postoperative complications and a trend toward lower mortality. Fourth, the annual cut-off of ≥ 20 MIPR and ≥ 20 MIPD improved selected outcome measures. Fifth, most MIPR were performed by a single surgeon. Sixth, only two-thirds of the centers performed spleen-preserving DP. Seventh, DP with splenectomy was associated with higher conversion rate when compared to spleen-preserving DP. Eighth, the use of pancreatojejunostomy was the prevalent reconstruction in PD. Ninth, final histology was similar for MIPR performed at high- and low-volume centers, but neoadjuvant chemotherapy was used more frequently at high-volume centers. Finally, this registry analysis raises important concerns about the reliability of R1 assessment underscoring the importance of standardized pathology of pancreatic specimens. In conclusion, MIPR can be safely implemented on a national scale. Further analyses are required to understand nuances of implementation of MIPR in Italy.

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.

Borderline resectable pancreatic cancer: Certainties and controversies.

Borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is currently a well-recognized entity, characterized by some specific anatomic, biological and conditional features: It includes patients with a stage of disease intermediate between the resectable and the locally advanced ones. The term BR identifies a tumour with an aggressive biological behaviour, on which a neoadjuvant approach instead of an upfront surgery one should be preferred, in order to obtain a radical resection (R0) and to avoid an early recurrence after surgery. Even if during the last decades several studies on this topic have been published, some aspects of BR-PDAC still represent a matter of debate. The aim of this review is to critically analyse the available literature on this topic, particularly focusing on: The problem of the heterogeneity of definition of BR-PDAC adopted, leading to a misinterpretation of published data; its current management (neoadjuvant vs upfront surgery); which neoadjuvant regimen should be preferably adopted; the problem of radiological restaging and the determination of resectability after neoadjuvant therapy; the post-operative outcomes after surgery; and the role and efficacy of adjuvant treatment for resected patients that already underwent neoadjuvant therapy.

Total pancreatectomy as alternative to pancreatico-jejunal anastomosis in patients with high fistula risk score: the choice of the fearful or of the wise?

PURPOSE: Patients with fistula risk score (FRS) ≥7 are at the highest risk of developing clinically relevant post-operative pancreatic fistula (CR-POPF). There is no agreement on the management of this subpopulation. The primary outcome of the study was the definition of the role of intraoperative completion pancreatectomy (ICP) in patients at high risk for CR-POPF, as an alternative to high-risk pancreaticoduodenectomy (PD). METHODS: This is an observational study set in a single tertiary referral center. Patients scheduled for PD in our center between 2010 and 2019 with FRS ≥7 were included in the study. Data were prospectively collected. RESULTS: A total of 738 patients were scheduled for between 2010 and 2019, and 62 had FRS ≥7. Thirty-five patients were managed with PD and pancreatico-jejunal anastomosis (group A), and 27 with ICP (group B). Overall complication rate was significantly higher in group A than group B (95 versus 59%; p=0.005) and there was a not significantly higher rate of major complications (Clavien-Dindo ≥3) (43 versus 26%; p=0.192). In group A, 49% of patients had a CR-POPF. Median post-operative length of stay was 15 days in group A and 12 in group B (p=0.043). Readmission was observed only in group A (26%). In multivariate analysis, PD was an independent predictive factor of major post-operative morbidity (RR 9.27; CI 1.74-49.31). No patients in either group suffered major adverse events related to endocrine and exocrine insufficiency. CONCLUSION: In high-FRS patients, ICP has good short-term outcomes relative to PD without major long-term events related to endocrine and exocrine insufficiency. ICP could be considered as a feasible alternative in selected cases.

Isolation of Proximal Fluids to Investigate the Tumor Microenvironment of Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death, and soon to become the second. There is an urgent need of variables associated to specific pancreatic pathologies to help preoperative differential diagnosis and patient profiling. Pancreatic juice is a relatively unexplored body fluid, which, due to its close proximity to the tumor site, reflects changes in the surrounding tissue. Here we describe in detail the intraoperative collection procedure. Unfortunately, translating pancreatic juice collection to murine models of PDAC, to perform mechanistic studies, is technically very challenging. Tumor interstitial fluid (TIF) is the extracellular fluid, outside blood and plasma, which bathes tumor and stromal cells. Similarly to pancreatic juice, for its property to collect and concentrate molecules that are found diluted in plasma, TIF can be exploited as an indicator of microenvironmental alterations and as a valuable source of disease-associated biomarkers. Since TIF is not readily accessible, various techniques have been proposed for its isolation. We describe here two simple and technically undemanding methods for its isolation: tissue centrifugation and tissue elution.

Enhanced Recovery After Pancreatic Surgery Does One Size Really Fit All? A Clinical Score to Predict the Failure of an Enhanced Recovery Protocol After Pancreaticoduodenectomy.

BACKGROUND: The inability to comply with enhanced recovery protocols (ERp) after pancreaticoduodenectomy (PD) is a real but understated issue. Our goal is to report our experience and a potential tool to predict ERp failure in order to better characterize this problem. METHODS: From January 1, 2014, to January 31, 2016, 205 consecutive patients underwent PD in our center and were managed according to an ERp. Failure to comply with postoperative protocol items was defined as any of: no active ambulation on postoperative day 1 (POD1); less than 4 h out of bed on POD2; removal of nasogastric tube and bladder catheter after POD1 and POD3, respectively; reintroduction of oral feeding after POD4; and continuation of intravenous infusions after POD4. Data were collected in a prospective database. RESULTS: Taking in consideration the number of failed items and the length of stay, we defined failure of the ERp as no compliance to two or more items. A total of 116 patients (56.6%) met this definition of failure. We created a predictive model consisting of age, BMI, operative time, and pancreatic stump consistency. These variables were independent predictors of failure (OR 1.03 [1.001-1.06] p = 0.01; OR 1.11 [1.01-1.22] p = 0.03; OR 1.004 [1.001-1.009] p = 0.02 and OR 2.89 [1.48-5.67] p = 0.002, respectively). Patient final score predicted the failure of the ERp with an area under the ROC curve of 0.747. CONCLUSIONS: It seems to be possible to predict ERp failure after PD. Patients at high risk of failure may benefit more from a specific ERp.

Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1+ Cells.

Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancreatic disorders. We investigated, by 1H nuclear magnetic resonance, the metabolomic fingerprint of pancreatic juice (the biofluid that collects pancreatic products) in 40 patients with different pancreatic diseases. Metabolic variables discriminated PDAC from other less aggressive pancreatic diseases and identified metabolic clusters of patients with distinct clinical behaviors. PDAC specimens were overtly glycolytic, with significant accumulation of lactate, which was probed as a disease-specific variable in pancreatic juice from a larger cohort of 106 patients. In human PDAC sections, high expression of the glucose transporter GLUT-1 correlated with tumor grade and a higher density of PD-1+ T cells, suggesting their accumulation in glycolytic tumors. In a preclinical model, PD-1+ CD8 tumor-infiltrating lymphocytes differentially infiltrated PDAC tumors obtained from cell lines with different metabolic consumption, and tumors metabolically rewired by knocking down the phosphofructokinase (Pfkm) gene displayed a decrease in PD-1+ cell infiltration. Collectively, we introduced pancreatic juice as a valuable source of metabolic variables that could contribute to differential diagnosis. The correlation of metabolic markers with immune infiltration suggests that upfront evaluation of the metabolic profile of PDAC patients could foster the introduction of immunotherapeutic approaches for pancreatic cancer.