A Digital Approach to Improve Infection Screening Among Solid Organ Transplant Candidates.

BACKGROUND: Pretransplant infection screening (IS) of potential organ recipients is essential to optimal outcome of solid organ transplantation (SOT). METHODS: A pre-post study was performed during 2020-2023 to investigate the impact of the STREAM (Solid organ TRansplant stEwArdship and Multidisciplinary approach) intervention to improve IS in SOT. The intervention, performed in 2022, included the implementation of IS through educational meetings, local guidelines, and the availability of a digital screening tool. The objective of the study was the assessment of IS completion, including a list of 17 laboratory tests and the investigation of vaccination status. The reduction of unnecessary tests was also analyzed. The test of proportions and a multilevel multivariate Poisson regression model were used to compare IS completion before and after STREAM. infectious diseases (ID) consultation and urgent evaluation were investigated as predictors of IS completion. RESULTS: A total of 171 patients were enrolled, including liver (44%), heart (32%), and kidney (24%) transplant candidates. Mean age was 56 ± 11 years, and most patients (77%) were males. Ninety-five (56%) patients were included before the intervention and 76 (44%) after STREAM. IS completion increased after STREAM (IRR 1.41, p < 0.001) with significant improvement recorded for seven (39%) IS items. Unnecessary tests decreased by 43% after the intervention. ID consultation (IRR 1.13, p = 0.02) and urgent evaluation (p = 0.68, p < 0.001) were predictors of IS improvement. CONCLUSIONS: STREAM was successful in improving IS completion. Further research is needed to investigate the impact of this intervention on posttransplant infections.

ABO-Incompatible Orthotopic Liver Transplant as a Rescue Strategy for Fulminant Hepatic Failure in a Recipient With Breast Cancer: Highlights on Transplant Management.

Pretransplant malignancy unrelated to hepatocellular carcinoma is a challenging condition in liver transplantation. Standard of care requires the completion of treatments and a disease-free period before the transplant. However, in the setting of a fulminant hepatic failure, these steps cannot be achieved. A 46-year-old woman with a recent diagnosis of stage 2 breast cancer presented to our center with a fulminant hepatic failure of unknown origin. Because of the rapid worsening of her clinical status, she was listed as eligible for transplant after a multidisciplinary evaluation. Because of a shortage of available donors, a deceased donor ABO-incompatible liver transplant with a synchronous mastectomy and first-level axillary lymphadenectomy was performed. To prevent antibody-mediated rejection, a triple immunosuppression therapy and a postoperative therapeutic plasmapheresis were performed. The patient remains without cancer recurrence at 18 months of follow-up. Recent studies have shown that cancer recurrence in recipients with pretransplant malignancy is considerably lower than suggested in previously published studies. However,this data is not sufficient to establish evidence-based guidelines on the indications and timing of transplant. In selected cases, the presence of a pretransplant malignancy does notrepresent a contraindication for a rescue liver transplant. Further studies are needed to stratify the risk and to help clinicians to choose the best strategy in an urgent context such as this.

Development of a preoperative score to predict surgical difficulty in liver transplantation.

BACKGROUND: A difficulty score to predict intraoperative surgical complexity in liver transplantation has never been developed. The aim of this study was to assess factors associated with a difficult liver transplant and develop a score to predict difficult surgery. METHODS: All patients undergoing deceased donor whole liver transplantation from 2012 to 2019 at a single center were included. Estimated intraoperative blood loss (mL/kg) and surgery duration (skin-to-arterial reperfusion time) were used as surrogates of difficulty. Based on these variables, the study population was divided into 2 groups: high risk and standard risk of difficulty. Univariate and multivariate analyses were performed to identify predictors associated with a demanding liver transplantation and develop a difficulty score. RESULTS: A total of 515 patients were included in the study population, and 101 (20%) were considered difficult operations. Patients with a higher risk of difficulty showed a significantly higher rate of Clavien-Dindo ≥III complications (50.5% vs 24.4%, P = .001) and a longer hospital stay (19 vs 16 days, P = .001). Preoperative factors associated with difficulty were retransplantation (odds ratio 4.34, P = .001), preoperative portal vein thrombosis (odds ratio 3.419, P = .001), previous upper abdominal surgery (odds ratio 2.161, P = .003), spontaneous bacterial peritonitis (odds ratio 1.985, P < .02), and prior variceal bleeding (odds ratio 1.401, P = .051). A 10-point difficulty score was created, showing a negative predictive value of 84% at 4 points. CONCLUSION: Difficult liver transplantation surgery, as assessed by skin-to-arterial reperfusion time and estimated blood loss, is associated with worse perioperative outcomes. We developed a simple score with clinical preoperative variables that predicts difficult surgery, and therefore, it may help to optimize allocation policies and perioperative logistics.

Carcinogenesis and Cancer Progression in De Novo Anal Squamous Cell Carcinoma After Organ Transplantation: A Systematic Review.

Our aim was to perform a comprehensive literature review on the pathogenesis of squamous anal cancerin patients after solid-organ transplant. Medical databases were consulted until June 1, 2020, for potentially relevant publications.All studies on pathogenesis of de novo anal squamous cell carcinoma in solid-organ transplant recipients were included. Two researchers independently performed study selection, quality assessment, and data extraction and analysis. Twenty-one studies were included.None ofthe selected papers had been solely focused on carcinogenesis. Most ofthe studies identified human papillomavirus infection and immunosuppression to be significantly correlated with the development of de novo anal cancer in adult solid organ transplant recipients. CD4+ T-cell depletion and inactivation oftumor suppressor pathways were mainly implicated. All solid-organ transplant recipients, especially those who were human papillomavirus positive, were shown to be at increased risk for the development of posttransplant anal cancer. Further studies are needed to determine the specific mechanisms of pathogenesis according to different solid-organ transplant populations.

A randomized controlled trial of stapled versus ultrasonic transection in distal pancreatectomy.

BACKGROUND: The pancreatic transection method during distal pancreatectomy is thought to influence postoperative fistula rates. Yet, the optimal technique for minimizing fistula occurrence is still unclear. The present randomized controlled trial compared stapled versus ultrasonic transection in elective distal pancreatectomy. METHODS: Patients undergoing distal pancreatectomy from July 2018 to July 2020 at two high-volume institutions were considered for inclusion. Exclusion criteria were contiguous organ resection and a parenchymal thickness > 17 mm on intraoperative ultrasound. Eligible patients were randomized in a 1:1 ratio to stapled transection (Endo GIA Reinforced Reload with Tri-Staple Technology®) or ultrasonic transection (Harmonic Focus® + or Harmonic Ace® + shears). The primary endpoint was postoperative pancreatic fistula. Secondary endpoints included overall complications, abdominal collections, and length of hospital stay. RESULTS: Overall, 72 patients were randomized in the stapled transection arm and 73 patients in the ultrasonic transection arm. Postoperative pancreatic fistula occurred in 23 patients (16%), with a comparable incidence between groups (12% in stapled transection versus 19% in ultrasonic dissection arm, p = 0.191). Overall complications did not differ substantially (35% in stapled transection versus 44% in ultrasonic transection arm, p = 0.170). There was an increased incidence of abdominal collections in the ultrasonic dissection group (32% versus 14%, p = 0.009), yet the need for percutaneous drain did not differ between randomization arms (p = 0.169). The median length of stay was 8 days in both groups (p = 0.880). Intraoperative blood transfusion was the only factor independently associated with postoperative pancreatic fistula on logistic regression analysis (OR 4.8, 95% CI 1.2-20.0, p = 0.032). CONCLUSION: The present randomized controlled trial of stapled versus ultrasonic transection in elective distal pancreatectomy demonstrated no significant difference in postoperative pancreatic fistula rates and no substantial clinical impact on other secondary endpoints.

Microwave ablation of colorectal liver metastases: Impact of a 10-mm safety margin on local recurrence in a tertiary care hospital.

Microwave ablation (MWA) for colorectal liver metastasis (CLM) has been traditionally considered inferior to surgery due to the higher rate of local recurrence. The study investigated whether a safety margin of 10 mm can improve local control in patients undergoing surgical MWA. Surgical MWA was used to treat 53 lesions in 22 patients with CLM at our Institution from June 2012 to June 2017. The patients' mean age was 64.5 years, and the median size of the lesion was 16.5 mm (9-34 mm). MWA was associated with liver resection in 16 patients (72.7%). The median follow-up was 32.4 months. Univariate and multivariate analyses were performed to identify factors associated with tumor recurrence. Median ablation area was 36.6 mm2 (30-50 mm2). The complication rate was 22.7%. No local recurrence was observed during follow-up. Disease-free survival was 20 months (4.8-55.2 months). Univariate analysis revealed that the number of liver metastases and node-positive primary tumors were associated with tumor recurrence. Multivariate analysis revealed that node-positive primary tumor was the only factor significantly associated with tumor recurrence (p = 0.049; odds ratio, 12; 95% confidence interval, 1-143). When performed with a 10-mm safety margin, surgical MWA can lead to acceptable oncological outcomes with low morbidity. Therefore, it represents a good option in selected patients with CLM.

Resource utilization and outcomes in emergency general surgery during the COVID19 pandemic: An observational cost analysis.

BACKGROUND: Over the course of the COVID19 pandemic, global healthcare delivery has declined. Surgery is one of the most resource-intensive area of medicine; loss of surgical care has had untold health and economic consequences. Herein, we evaluate resource utilization, outcomes, and healthcare costs associated with unplanned surgery admissions during the height of the pandemic in 2020 versus the same period in 2019. METHODS: Retrospective analysis on patients ≥18 years admitted from the emergency department to General & Digestive and Gastrointestinal Surgery Services between February and May 2019 and 2020 at our center; clinical outcomes and unadjusted and adjusted per-person healthcare costs were analyzed. RESULTS: Consults and admissions to surgery declined between February and May 2020 by 37% and 19%, respectively, relative to the same period in 2019, with even greater relative decline during late March and early April. Time between onset of symptoms to diagnosis increased from 2±3 days 2019 to 5±22 days 2020 (P = 0.01). Overall hospital stay was two days less in 2020 (P = 0.19). Complications (Comprehensive Complication Index 10.3±23.7 2019 vs. 13.9±25.5 2020, P = 0.10) and mortality rates (3% vs. 4%, respectively, P = 0.58) did not vary. Mean unadjusted per-person costs for patients in the 2019 and 2020 cohorts were 5,886.72€±12,576.33€ and 5,287.62±7,220.16€, respectively (P = 0.43). Following multivariate analysis, costs remained similar (4,656.89€±390.53€ 2019 vs. 4,938.54±406.55€ 2020, P = 0.28). CONCLUSIONS: Healthcare delivery and spending for unplanned general surgery admissions declined considerably due to COVID19. These results provide a small yet relevant illustration of clinical and economic ramifications of this healthcare crisis.

Diffuse Micro-Nodules on Peritoneal Surfaces at Donor Organ Procurement: Highlights on the Diagnostic Challenge and Transplant Management.

BACKGROUND Guidelines have been designed to stratify the risk of cancer transmission in donors with a history of or ongoing malignancy, although this evaluation is not always straightforward when unexpected and rare lesions are found. CASE REPORT Here, we present a case of a 41-year-old African female donor who died from a cerebral hemorrhage. Her medical history was unavailable. At procurement, multiple diffuse grayish small nodules were noticed along the peritoneal cavity, some of which were sent to the on-call pathologist for urgent frozen section evaluation. Histology showed a multinodular proliferation of uniform bland-appearing spindle cells, with no evidence of necrosis, nor nuclear atypia or mitoses. The overall picture was consistent with the diagnosis of disseminated peritoneal leiomyomatosis, with overlapping morphology with uterine leiomyoma. Given the rarity of the lesion and the potential for recurrence or malignant degeneration, only the liver and heart were allocated to recipients with life-threatening conditions. The decision was taken in a forcedly limited time and took into account the benefit of transplantation and the risk of disease transmission. CONCLUSIONS This case highlights challenges that transplant teams often have to deal with, as lesions that are difficult to diagnose during donor assessment are usually not covered in guidelines. The acceptance and usage of organs in such cases has to be decided in a team-based fashion, with the collaboration of all the transplant professionals involved to optimally assess the transmission risk, carefully balancing the benefits of transplantation for the recipients and the need to guarantee a reasonable degree of safety.

Multifactorial mitigation strategy to reduce clinically relevant pancreatic fistula in high-risk pancreatojejunostomy following pancreaticoduodenectomy.

INTRODUCTION: Postoperative pancreatic fistula (POPF) is the most dreadful complication of pancreaticoduodenectomy (PD) and previous literature focused on technical modifications of pancreatic remnant reconstruction. We developed a multifactorial mitigation strategy (MS) and the aim of the study is to assess its clinical impact in patients at high-risk of POPF. METHODS: All patients candidate to PD between 2012 and 2018 were considered. Only patients with a high Fistula Risk Score (FRS 7-10) were included. Patients undergoing MS were compared to patients receiving Standard Strategy (SS). Clinical outcomes were compared between the two groups. Multivariate hierarchical logistic regression analyses were performed to detect independent predictors of POPF. RESULTS: Out of 212 patients, 33 were finally included in MS Group and 29 in SS Group. POPF rate was significantly lower in MS Group (12.1% vs 44.8%, p = 0.005). Delayed gastric emptying, postoperative pancreatitis, complications and hospital stay were also significantly lower in MS Group. Hierarchical logistic regression analyses showed that Body Mass Index (OR = 1.196, p = 0.036) and MS (OR = 0.187, p = 0.032) were independently associated with POPF. CONCLUSION: A multifactorial MS can be helpful to reduce POPF rate in patients with high FRS following PD. Personalized approach for vulnerable patients should be investigated in the future.

Clinical impact of preoperative tumour contact with superior mesenteric-portal vein in patients with resectable pancreatic head cancer.

INTRODUCTION: The NCCN classification of resectability in pancreatic head cancer does not consider preoperative radiological tumour ≤ 180° contact with portal vein/superior mesenteric vein (PV/SMV) as a negative prognostic feature. The aim of this study is to evaluate whether this factor is associated with higher rate of incomplete resection and poorer survival. METHODS: All patients considered for pancreatic resection between 2012 and 2017 at two Spanish referral centres were included. Patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC) according to NCCN classification were excluded. Preoperative CT scans were reviewed by dedicated radiologists to identify radiologic tumour contact with PV/SMV. RESULTS: Out of 302, 71 patients were finally included in this study. Twenty-two (31%) patients showed tumour-PV/SMV contact (group 1) and 49 (69%) did not show any contact (group 2). Patients in group 1 showed a statistically significantly higher rate of R1 and R1-direct margins compared with group 2 (95 vs 28% and 77 vs 10%) and lower median survival (24 vs 41 months, p = 0.02). Preoperative contact with PV/SMV, lymph node metastases, R1-direct margin and NO adjuvant chemotherapy were significantly associated with disease-specific survival at multivariate analysis. CONCLUSION: Preoperative radiological tumour contact with PV/SMV in patients with NCCN resectable PDAC is associated with high rate of pathologic positive margins following surgery and poorer survival.

Primary pancreatic lymphoma: Clinical presentation, diagnosis, treatment, and outcome.

Primary pancreatic lymphoma (PPL) is a rare disease representing 0.1% of malignant lymphomas, which lacks well-defined diagnostic and therapeutic protocols. OBJECTIVES: To describe PPL clinical, diagnostic and histological characteristics, together with therapy and outcome, in a relatively large series of patients. METHODS: The study includes 39 PPL patients, aged ≥15 years, observed from January 2005 to December 2018, in 8 Italian Institutions. RESULTS: The main symptoms were abdominal pain (58%) and jaundice (47%). Lactate dehydrogenase serum levels were elevated in 43% of patients. Histological specimens were mostly obtained by percutaneous (41%) or endoscopic (36%) biopsy, with diffuse large B-cell lymphoma being the most frequent (69%) histological diagnosis. Chemotherapy was administered alone in 65% of patients, with radiotherapy in 17%, or after surgery in 9%. The 2-year overall survival (OS) was 62%, the 2-year progression-free survival (PFS) 44%. Debulking surgery (with or without chemotherapy) was associated with a significant worse OS. Three (9.4%) of 32 high-grade patients experienced a central nervous system (CNS) relapse. CONCLUSIONS: PPL is rare, often high-grade, with symptoms and localization similar to other pancreatic malignancies. Biopsy should be the preferred diagnostic method. High-grade PPL should undergo CNS prophylaxis.

Factors associated with mortality in patients with infected pancreatic necrosis: the "surgery effect".

Severe acute pancreatitis complicated by infection is associated with high mortality. Invasive treatment is indicated in the presence of infected (suspected) pancreatic and/or peripancreatic necrosis (IPN) in the absence of response to intensive medical support. Step-up approach (SUA) has been demonstrated to lower complication rate compared to upfront open surgery. However, this approach has not been associated with lower mortality, and no factors have been studied that could help to identify the high risk patients. In this study, we aimed to analyse those factors associated with mortality following the invasive treatment of IPN, focusing on the role of surgical necrosectomy. A retrospective and observational study based on a multicentre prospective database was conducted. The database was coordinated by the Hospital General Universitario de Alicante, Spain and the Spanish Association of Pancreatology. Demographics, clinical data, and laboratory and imaging findings were collected. Atlanta 2012 criteria were considered to classify acute necrotizing pancreatitis and for the definition of IPN. Step-up approach was used in all centres with the intention of avoiding surgery whenever possible. Surgical necrosectomy was performed by open approach. From January 2013 to October 2014, a total of 1655 patients with the diagnosis of acute pancreatitis were included in our database. 1081 were recruited for the final analysis. Out of them, 205 (19%) were classified into acute necrotizing pancreatitis. 77 (8.3%) patients underwent invasive treatment of INP and were included in our study. Overall mortality was 29.9%. Upfront endoscopic or percutaneous drainage was performed in 60 (77.9%) patients and mortality was 26.6%. Out of 60, 22 (36.6%) patients subsequently received rescue surgery; mortality in rescue surgery group was 18.3%. Upfront surgery was carried out in 17 (22.1%) patients; mortality in this group was 41%. At univariate analysis, surgical necrosectomy, extrapancreatic infection, immunosuppression and de-novo haemodialysis were associated with mortality. At multivariate analysis, only surgical necrosectomy was significantly associated with mortality (p = 0.002 OR 3.89). Surgical approach for IPN is associated with high mortality rate. However, these data should be interpreted with caution, since we are not able to assess whether this occurs due to the need of surgery as the only resort when the other approaches are not feasible or fail.

Implementation of a strategic preoperative surgical meeting to improve the level of care at a high-volume pancreatic center: a before-after analysis of 1000 consecutive cases.

The indication, planning, and risk analysis of a pancreatic surgical procedure have recently become increasingly complex. In December 2015, the "Pancreas Round" (PR) meeting was established at our institution to preoperatively review all scheduled cases with a specific focus on surgical indications and technical issues. The present study aims to determine the impact of the PR on the clinical practice in terms of avoiding unrequested laparotomies and anticipating intraoperative pitfalls. A "before-after" study was conducted by retrospectively comparing a pre-intervention period (9/2014-11/2015) to a prospectively assessed post-intervention one (12/2015-3/2017). Outcomes considered were explorative laparotomy (EL) occurrence and a "mismatch" between what was preoperatively expected by the PR and what was intraoperatively found. Of the 1057 patients included in the present study, 531 underwent surgery in the pre- and 526 in the post-intervention period, respectively. The EL rate was comparable between the two periods (15.4% vs. 12.2%, p = 0.123), despite the significant increase of surgical explorations after neoadjuvant chemotherapy during the post-intervention period (27% vs. 18%, p < 0.001). The "mismatch" rate between preoperative planning and intraoperative findings was significantly reduced in the post-intervention period (12.2% vs. 8.4%, p = 0.038) compared to the pre-PR period. In the setting of a high-volume center, a preoperative surgical meeting designed to review all cases scheduled for surgical exploration can enhance the level of care by addressing intraoperative pitfalls.

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.

Reinforced stapler versus ultrasonic dissector for pancreatic transection and stump closure for distal pancreatectomy: A propensity matched analysis.

BACKGROUND: Postoperative pancreatic fistula is the primary contributor to morbidity after distal pancreatectomy. To date, no techniques used for the transection and closure of the pancreatic stump have shown clear superiority over the others. This study aimed to compare the rate of postoperative pancreatic fistula after pancreatic transection conducted with a reinforced stapler versus an ultrasonic dissector after a distal pancreatectomy. METHOD: Prospectively collected data of consecutive patients who underwent distal pancreatectomy from 2014 to 2017 were reviewed retrospectively. We included distal pancreatectomies in which pancreatic transection was performed by reinforced stapler or ultrasonic dissector; we excluded extended distal pancreatectomies. To overcome the absence of randomization, we conducted a propensity matching analysis according to risk factors for postoperative pancreatic fistula. RESULTS: Overall, 200 patients met the inclusion criteria. The reinforced stapler was employed in 108 patients and the ultrasonic dissector in 92 cases. After one-to-one propensity matching, 92 patients were selected from each group. The matched reinforced stapler and ultrasonic dissector cohort had no differences in baselines characteristics except for the mini-invasive approach, which was more common in the ultrasonic dissector group (34% vs 51%, P = .025). Overall, 48 patients (26%) developed a postoperative pancreatic fistula, 46 (25%) a grade B postoperative pancreatic fistula, and 2 (1%) a grade C postoperative pancreatic fistula. In the reinforced stapler group, the rate of postoperative pancreatic fistula was 12% (n = 11) and in the ultrasonic dissector group 40% (n = 37) with a P < .001. CONCLUSION: The results of this study suggest that the use of reinforced stapler for pancreatic transection decreases the risk of postoperative pancreatic fistula. A randomized trial is required to confirm these preliminary data.

The Clinical Management of Main Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas comprise a heterogeneous group of intraductal mucin-producing neoplasms representing a typical adenoma-to-carcinoma sequence. The involvement of the main pancreatic duct (MPD) is a feature of paramount importance, directly related to a more aggressive biology and a higher malignancy rate. METHOD: We review and discuss the clinical management of IPMNs with a MPD involvement, recalling the different consensus guidelines and addressing recent controversies in literature, presenting the current clinical practice in Verona Pancreas Institute. RESULTS: All the aspects of surgical management were discussed, from the indication for surgery to the intraoperative management and the follow-up strategies. CONCLUSION: The management of presumed IPMNs involving the MPD at our Institution is in line with the International Association of Pancreatology 2012 guidelines, revised in 2016. Surgical resection proposed should achieve the complete removal of the tumor with negative margins. Despite a good prognosis in terms of survival of overall resected main duct intraductal papillary mucinous neoplasms, follow-up should not be discontinued.

Systematic review, meta-analysis, and a high-volume center experience supporting the new role of mural nodules proposed by the updated 2017 international guidelines on IPMN of the pancreas.

BACKGROUND: Mural nodules (MNs) have a predominant role in the 2016 revision of the international guidelines on intraductal papillary mucinous neoplasms (IPMN) of the pancreas. The aim of this study was to evaluate MNs as predictors of invasive cancer (iCa) or high-grade dysplasia (HGD) in IPMNs and to investigate the role of MN size in risk prediction. METHODS: A PRISMA-compliant systematic review of the literature and meta-analysis on selected studies were conducted. The random effect model was adopted, and the pooled SMD (standardized mean difference) obtained. The surgical series of IPMNs at a single high-volume institution was reviewed. RESULTS: This review included 70 studies and 2297 resected IPMNs. MNs have a positive predictive value for malignancy of 62.2%. The meta-analysis suggested that MN size has a considerable effect on predicting IPMNs with both iCa or HGD with a mean SMD of 0.79. All studies included in the meta-analysis used contrast-enhanced endosonography (CE-EUS) to assess MNs. Due to the heterogeneity of the proposed thresholds, no reliable MN size cut-off was identified. Of 317 IPMNs resected at our institution, 102 (32.1%) had a preoperative diagnosis of MN. Multivariate analysis showed that MN is the only independent predictor of iCa and HGD for all types of IPMNs. CONCLUSION: MNs are reliable predictors of iCa and HGD in IPMNs as proposed by the 2016 IAP guidelines. CE-EUS seems to be the best tool for characterizing size and has the best accuracy for predicting malignancy. Further studies should determine potential MN dimensional cut-offs.

Association between pancreatic intraductal papillary mucinous neoplasms and extrapancreatic malignancies.

BACKGROUND & AIMS: The association between pancreatic intraductal papillary mucinous neoplasms (IPMNs) and extrapancreatic neoplasms (EPNs) is controversial. We performed a multicenter observational study to assess the incidence of EPNs after an IPMN diagnosis. METHODS: 1340 patients with IPMNs were evaluated from 2000 through 2013 at 4 academic institutions in Europe for development of EPN. To estimate the actual incidence of EPN, we excluded patients with an EPN previous or synchronous to the IPMN, and patients who had been followed for less than 12 months, resulting in a study population of 816 patients. The incidence of EPN was compared with sex-specific, age-adjusted European cancer statistics; the standardized incidence ratio (SIR), and the 5- and 10-year cumulative incidence rates were calculated. RESULTS: A total of 290/1340 patients had a history of EPN (prevalence of 21.6%). In this subgroup of patients, the IPMN was discovered incidentally in 241. Among the 816 patients included in the incidence analysis, 50 developed an EPN after a median time of 46 months from study enrollment. The incidence of any EPN was not greater in patients with than without IPMN with a SIR of 1.48 (95% confidence interval, 0.94-2.22) in males and of 1.39 (95% CI 0.90-2.05) in females. The 5- and 10-year cumulative incidence rates for development of EPN in patients with IPMN were 7.9% and 16.6% in men, and 3.4% and 23.1% in women. CONCLUSIONS: Patients with IPMN do not have a significantly higher incidence of EPNs than the general European population. It might not be necessary to screen patients with IPMN for EPN.

Observational study of the incidence of pancreatic and extrapancreatic malignancies during surveillance of patients with branch-duct intraductal papillary mucinous neoplasm.

OBJECTIVE: This observational analysis assessed the incidence of pancreatic and extrapancreatic malignancies in BD-IPMN patients. BACKGROUND: Previous studies showed that progression to malignancy of pancreatic branch-duct (BD) intraductal papillary mucinous neoplasm (IPMN) is infrequent and that extrapancreatic malignancies (EPMs) occur with unusual frequency in IPMN patients. METHODS: Patients observed from 2000 to 2012 and enrolled in a surveillance protocol according to the current guidelines were considered eligible for the study. Only patients with follow-up of more than 12 months were evaluated. The incidence of EPM was calculated only in patients who were free of them at the time of IPMN diagnosis. Data were compared with Italian cancer statistics. The standardized incidence ratios (SIRs) and the 5- and 10-year incidence rates were estimated. RESULTS: The study population consisted of 569 patients. At a median follow-up of 56 months, 9 patients developed a pancreatic malignancy. Of these, 5 were unresectable. The SIR was 9.21 [95% confidence interval (CI), 1.85-26.91] in males, and 11.94 (95% CI, 4.36-26.0) in females, with a 5-year cumulative incidence of 1.4%. The EPM incidence analysis was performed in 456 patients. Thirty EPMs developed during the follow-up. The SIR was 1.40 (95% CI, 0.72-2.45) in males and 1.37 (95% CI, 0.81-2.16) in females. The 5-year rate of developing any EPM was 5.7%. CONCLUSIONS: BD-IPMN patients are at risk of pancreatic carcinogenesis. Although the 5-year incidence rate was as low as 1.4%, the surveillance protocol based on the current guidelines failed to identify a small subset of patients who progressed to advanced disease. Patients with BD-IPMN are not at risk of extrapancreatic carcinogenesis.