BACKGROUND:Pancreatogenic diabetes, a consequence of pancreatic tissue loss following pancreatectomy, poses a significant challenge for patients undergoing pancreatic surgery. Islet autotransplantation (IAT) offers a promising approach to prevent or alleviate pancreatogenic diabetes, but its application has been limited to individuals with painful chronic pancreatitis. METHODS:This study presents a 15-y clinical experience with the Milan Protocol, which expands IAT after pancreatectomy to a broader spectrum of patients with malignant and nonmalignant pancreatic diseases. The analysis evaluates feasibility, efficacy, and safety of IAT. Modified Igls criteria validated through the arginine test and mixed meal tolerance tests were used to assess long-term metabolic outcomes. RESULTS:Between November 2008 and June 2023, IAT procedures were performed on 114 of 147 candidates. IAT-related complications occurred in 19 of 114 patients (16.7%), with 5 being potentially serious. Patients exhibited sustained C-peptide secretion over the 10-y follow-up period, demonstrating a prevalence of optimal and good beta-cell function. Individuals who underwent partial pancreatectomy demonstrated superior metabolic outcomes, including sustained C-peptide secretion and a reduced risk of developing diabetes or insulin dependence compared with those who underwent total pancreatectomy. For patients who had total pancreatectomy, the quantity of infused islets and tissue volume were identified as critical factors influencing metabolic outcomes. An increased risk of recurrence or progression of baseline diseases was not observed in subjects with neoplasms. CONCLUSIONS:These findings provide valuable insights into the benefits and applications of IAT as a therapeutic option for pancreatogenic diabetes after pancreatic surgery, expanding its potential beyond painful chronic pancreatitis.

Introduction: Infections caused by multidrug-resistant bacteria (MDR) occur more frequently after pancreaticoduodenectomy (PD) compared to other abdominal surgeries, and infective complications represent a major determinant of postoperative morbidity following PD. Preoperative biliary stent (PBS) placement often leads to biliary contamination, which plays a significant role in postoperative infections. The aim of this study is to evaluate the impact of MDR contamination on short-term postoperative outcomes in patients undergoing PD and to evaluate the relationship between MDR bacteria, PBS, and bile contamination. Methods: This is a retrospective study based on a prospectively maintained database including 825 consecutive patients who underwent pancreaticoduodenectomies (PDs). All procedures were performed by experienced pancreatic surgeons at a high-volume center and the patients were managed according to the same perioperative enhanced recovery protocol. Results: MDR bacteria were present in 17.5% of bile cultures, exclusively within the stented group. At the multivariate analysis, the development of major postoperative complications (MPC) was correlated with the presence of MDR bacteria in the bile (OR 1.66, 95% CI: 1.1–2.52; p = 0.02). MDR bacteria were detected early in the surgical drainage in 144 out of 825 patients (12.1%), with 72.2% having a previous biliary stent placement and 27.8% without stents (p < 0.001). Moreover, the development of an MPC was associated with the presence of MDR bacteria in the drainage (OR = 1.81, 95% CI: 1.21–2.73, p = 0.0042). Conclusions: We demonstrated that MDR contamination worsens the short-term outcomes of patients undergoing PDs. Specifically, when MDR bacteria are present in both the bile and drainage, there is a statistically significant increase in the incidence of major postoperative complications (MPC). Our data suggest that the majority of MDR surgical site infections stem from biliary contamination resulting from the placement of a preoperative biliary stent (PBS).

Background: Previous studies showed that bacterial contamination of surgical drains was associated with higher morbidity and mortality following pancreaticoduodenectomy (PD). However, there is still no agreement on the routine use of fluid drainage cultures in the management of patients underwent PD. Therefore, we aimed to clarify the role of surgical drain bacterial contamination in predicting patients' postoperative course. Method: Single-centre study including patients underwent PD at Humanitas Research Hospital (2010-2021). Preoperative, intraoperative and postoperative data were collected. Routinely performed fluid drain cultures on postoperative day (POD) 5 were analyzed and compared among patients throughout the cohort. Results: A total of 825 patients were analyzed. Bacterial contamination of surgical drains was observed in 420 (50.9 %) patients and it was found to be associated with a higher rate of B/C grade pancreatic fistula (POPF) (P < 0.001), Clavien-Dindo >= 3 (P < 0.001), 30-day mortality (P = 0.011), wound infection (P < 0.001), relaparotomies (P = 0.003) and greater length of hospital stay (LOS) (P < 0.001). Also, E. coli surgical drain contamination was demonstrated to double the risk of B/C grade POPF development (OR = 1.628, 95 % IC = 1.009-2.625, P = 0.046). Finally, preoperative biliary drainage (OR = 2.474, 95 % IC = 1.855-3.298, P < 0.001), age >= 75 years old (OR = 1.492, 95 % IC = 1.077-2.067, P = 0.016) and isolated Roux-en-Y pancreaticojejunostomy (OR = 1.639, 95 % IC = 1.229-2.188, P < 0.001) were identified as risk factors for surgical drains bacterial contamination. Conclusion: Bacterial contamination of surgical drains predicts the development of B/C grade POPF and other major complications after PD. Therefore, we suggest the routine use of fluid drain cultures following PD.

Gastrointestinal tract breast cancer (BC) metastases represent a rare event and generally originate from the lobular subtype. Duodenal involvement was rarely described in previous case series. Abdominal symptoms are extremely unspecific and misleading. Diagnosis is challenging, and it consists of a few mandatory steps from radiological examinations to histological and immunohistochemical analyses. Here, we presented the clinical case of a 54-year-old postmenopausal woman who was hospitalized for vomiting and jaundice, presenting increased level of liver enzymes and minimal main bile duct and choledocus dilatation at abdominal ultrasonography. She underwent breast-conserving surgery and axillary lymph node dissection for stage IIIB lobular BC, 5 years before. Metastatic infiltration of the duodenal bulb originating from lobular BC was proven histologically, through fine-needle aspiration during endoscopic ultrasonography. Treatment was established after multidisciplinary team evaluation, based on the clinical status and prognosis of the patient. Pancreaticoduodenectomy was performed, and final histological examination confirmed the secondary localization of lobular BC, infiltrating the duodenal and gastric wall, pancreas parenchyma, and surrounding tissues. No metastatic lymph nodes were found. After surgery, the patient underwent first line of adjuvant systemic treatment with fulvestrant and ribociclib. After a follow-up of 21 months, the patient was in good clinical condition, without signs of locoregional or distant recurrence. This report stressed on the importance of a tailored therapeutic approach. Although systemic therapy generally represents the preferred option, surgery should not be excluded if an oncological radical resection can be performed achieving acceptable locoregional disease control.

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.

W e thank Dr Leo Hans Buhler and colleagues for their keen interest in our study 1 and the editor for the opportunity to respond to the issues that were raised. The PAN-IT trial recruited patients with pancreatic ductal adenocarcinoma (PDAC) and various other neoplastic disorders. Buhler and colleagues pointed out that in our study the proportion of patients with PDAC was 9 of 31 (29%) versus 5 of 30 (16.7%) for the pancreaticoduodenectomy (PD) and total pancreatectomy (TP-IAT) groups, respectively, and suggested that this difference (although nonsignificant: P = 0.36, Fisher exact test) may have favored TP-IAT over PD when assessing the outcomes of our trial, particularly disease-specific and overall survival. As reported in the article, to avoid imbalance in the severity of neoplastic disease between the 2 groups, we allocated patients to study treatment by minimization, to balance periampullary adenocarcinoma (including PDAC, ampullary adenocarcinoma, distal bile adenocarcinoma, and duodenum carcinoma) versus other neo-plastic, benign or borderline lesions in the 2 groups. Randomization was indeed successful, as the proportion of patients with periamp-ullary adenocarcinoma was 24 (PDAC n = 9) of 31 (77.4%) versus 21 (PDAC n = 5) of 30 (70%), for PD and TP-IAT, respectively ( P = 0.57, Fisher exact test). To respond to the concern of Buhler and colleagues, we performed additional analyses of our data. However, numbers in the presented subanalyses are low and, therefore, results

Many tumors may secondarily involve the pancreas; however, only retrospective autopic and surgical series are available. We retrospectively collected data from all consecutive patients with histologically confirmed secondary tumors of the pancreas referred to five Italian centers between 2010 and 2021. We described clinical and pathological features, therapeutic approach and treatment outcomes. EUS characteristics of the lesions and the tissue acquisition procedures (needle, passages, histology) were recorded. A total of 116 patients (males/females 69/47; mean age 66.7) with 236 histologically confirmed pancreatic metastases were included; kidney was the most common primary site. EUS was performed to confirm the diagnosis in 205 lesions which presented as predominantly solitary (59), hypoechoic (95) and hypervascular (60), with a heterogeneous (n = 54) pattern and well-defined borders (n = 52). EUS-guided tissue acquisition was performed in 94 patients with an overall accuracy of 97.9%. Histological evaluation was possible in 88.3% of patients, obtaining final diagnosis in all cases. When cytology alone was performed, the final diagnosis was obtained in 83.3% of cases. A total of 67 patients underwent chemo/radiation therapy, and surgery was attempted in 45 (38.8%) patients. Pancreatic metastases are a possible event in the natural history of solid tumors, even long after the diagnosis of the primary site. EUS-guided fine needle biopsy may be suggested to implement the differential diagnosis.

Background: Pancreatoblastoma (PB) is a rare malignant epithelial tumor of the pancreas, mainly occurring in pediatric population. Pancreatoblastoma of the adult is extremely rare and usually shows a more aggressive biological behavior and a worse prognosis. Case Presentation: The patient was a 54-year-old man admitted for abdominal pain and weight loss. A computed tomography (CT) scan showed a 12 cm heterogeneous hypoattenuating mass in the pancreatic head. An endoscopic ultrasound-guided biopsy suggested the diagnosis of pancreatoblastoma (PB). The patient underwent a pancreaticoduodenectomy (PD) combined with limited liver resections for intraoperative finding of multiple liver metastasis. Pathological findings confirmed the diagnosis of PB metastatic to the liver. The tumor recurred in the liver 5 months after surgery and the patient succumbed due to tumor dissemination 8 months after initial diagnosis. Conclusion: Adult pancreatoblastoma is a rare pancreatic neoplasm with malignant behavior. The aim of this manuscript is to report our experience with pancreatoblastoma in the adult and to contribute improving knowledge about the clinical behavior of this rare and aggressive malignancy.

Background/Aim: Whether the presence of bacteria in the bile or postoperative infections sustained by microorganisms with different levels of drug-resistance are associated with changes in the oncologic prognosis of patients undergoing surgery for pancreatic cancer has not been thoroughly investigated. The aim was to study the association of bile contamination, postoperative infections, and multi-level resistance with long-term outcome. Patients and Methods: Prospectively maintained databases were queried for patients who underwent pancreatoduodenectomy (PD). Patients who underwent preoperative biliary stenting prior to PD and an intraoperative bile culture were included. The levels of bacterial resistance of intraoperative bile cultures and of specimens of postoperative infections were stratified into multidrug sensitive (MDS), multidrug-resistant (MDR), and extensive drug-resistant (XDR). Results: A total of 267 patients met the inclusion criteria. The Kaplan-Meier survival curves for overall survival (OS) of patients having no bacteriobilia or positive cultures with MDS versus MDR/XDR bacteria were not statistically different (logrank=0.9). OS of patients stratified for no postoperative infection or infections by MDS was significantly better than those having MRD/XDR isolates (log-rank=0.04). A Cox multivariate model showed that having MRD/XDR postoperative infections was and independent variable for worse OS (HR=1.227; 95%CI=1.1891.1918; p=0.036). Conclusion: Postoperative drug resistant infections are a significant risk factor for poor OS after pancreatoduodenectomy for ductal adenocarcinoma.

This record contains data related to article “Invasive IPMN relapse later and more often in lungs in comparison to pancreatic ductal adenocarcinoma” Background: The different oncological outcomes of invasive intraductal papillary mucinous neoplasm (I-IPMN) and pancreatic ductal adenocarcinoma (PDAC) are debated. This study aimed to compare disease recurrence patterns and histopathological characteristics in patients with resected I-IPMN and PDAC. Methods: Consecutive patients undergoing surgical resection for stage I-III I-IPMN or PDAC between 2010 and 2016 were retrospectively analyzed. Patients treated with neoadjuvant therapy or resected for Tis neoplasia were excluded. All surgical specimens were re-staged according to AJCC-8th-edition. Results: A total of 330 patients were included, of whom 43 had I-IPMN and 287 had PDAC. Median follow-up time was 26.7 (1.3-92.3) months and estimated median disease-free survival (DFS) was 60.3 months (47.2-73.4) for I-IPMN and 23.8 (19.3-28.2) months for PDAC (p < 0.001). During follow-up, 32.6% of I-IPMN and 67.9% of PDAC patients experienced recurrence (p < 0.001). The sites of first recurrence were the lungs (38.5% vs 13.1%, p = 0.027), liver (28.6% vs 45.0%, p = 0.180) and local (15.4% vs 36.6%, p = 0.101) for I-IPMN and PDAC, respectively. At multivariate analysis, I-IPMN histology remained an independent predictive factor for longer DFS (OR 0.528, CI 95% 0.278-1.000, p = 0.050), regardless of stage or adjuvant chemotherapy. I-IPMN and PDAC differed in rates of neuroinvasion (51.2% vs 97.2%) and positive lymph node status (N+) (46.5% vs 82.7%), especially in patients with lower T status. Conclusion: I-IPMN showed a different recurrence pattern compared to PDAC, with a higher lung tropism, and longer DFS. This different biological behavior is associated with lower rates of neuroinvasion and nodal involvement, especially in early-stage disease.

Postoperative pancreatic fistula (POPF) remains a major complication after distal pancreatectomy (DP) with a significant impact on patients’ quality of life. There is limited evidence that preservation of the spleen reduces the risk of POPF. Therefore, we aimed to investigate the impact of splenectomy on perioperative outcome.Data from patients who underwent DP for malignant and benign disease at our institution between 2004 and 2021 were reviewed. Patients were grouped according to spleen preservation (SP-DP) and splenectomy (DPS). Intraoperative parameters and postoperative outcomes were compared between groups. Univariable and multivariable analyses were used to investigate factors that influence the occurrence of clinically relevant (cr)POPF.A total of 199 patients were included, of whom 61 (30.7%) patients underwent SP-DP. Patients who underwent SP-DP had a significantly lower rate of crPOPF (p = 0.022), shorter hospital stay (p = 0.003), and less readmissions (p = 0.012). On multivariate analysis, obesity (OR 2.88, p = 0.021), benign lesions (OR 2.35, p = 0.018), postoperative acute pancreatitis (OR 2.53, p = 0.028), and splenectomy (OR 2.83, p = 0.011) were independent risk factors associated with the onset of crPOPF.Preservation of the spleen reduces the risk of crPOPF in patients undergoing distal pancreatectomy for benign and malignant disease.

Successful ductal access is achieved in 90% of patients who undergo ERCP. Precut sphincterotomy has been advocated when routine cannulation is not possible.To evaluate the efficacy of precut sphincterotomy for ductal access and the risk of adverse events including post-ERCP pancreatitis (PEP) associated with it.Retrospective analysis of ERCP procedures performed from 2002 to 2011.Referral center.A total of 10,202 consecutive patients who underwent native cannulation ERCP.Efficacy for ductal access and risk of adverse events including PEP.A total of 706 patients required precut sphincterotomy, 614 of whom (86.9%) had successful biliary cannulation. PEP was diagnosed in 58 (8.2 %), perforation in 6 (0.8%), and bleeding in 49 (6.9%) patients. On multivariate analysis, unsuccessful precut sphincterotomy (odds ratio [OR] 2.59; 95% confidence interval [CI], 1.53–4.40; P < .001) and female sex (OR 1.95; 95% CI, 1.23-3.07; P = .004) were associated with increased risk of the development of adverse events. Female sex (OR 2.42; 95% CI, 1.29-4.55; P = .006) and sphincter of Oddi dysfunction (OR 2.77; 95% CI, 1.16-6.60; P = .02) were associated with an increased risk of PEP.Retrospective study.Precut sphincterotomy is effective in achieving ductal access when standard cannulation techniques fail. A successful precut sphincterotomy is not associated with an increased risk of adverse events.