Potential Health Disparities in the Early Detection and Prevention of Pancreatic Cancer.

INTRODUCTION: Pancreatic cancer remains one of the deadliest cancers in the United States. Some types of pancreatic cysts, which are being detected more frequently and often incidentally on imaging, have the potential to develop into pancreatic cancer and thus provide a valuable window of opportunity for cancer interception. Although racial disparity in pancreatic cancer has been described, little is known regarding health disparities in pancreatic cancer prevention. In the present study, we investigate potential health disparities along the continuum of care for pancreatic cancer. METHODS: The racial and ethnic composition of pancreatic patients at high-volume centers in Indiana were evaluated, representing patients undergoing surgery for pancreatic cancer (n=390), participating in biobanking (972 pancreatic cancer patients and 1984 patients with pancreatic disease), or being monitored for pancreatic cysts at an early detection center (n=1514). To assess racial disparities and potential differences in decision-making related to pancreatic cancer prevention and early detection, an exploratory online survey was administered through a volunteer registry (n=708).  Results: We show that despite comprising close to 10% or 30% of the Indiana or Indianapolis population, respectively, African Americans make up only about 4-5% of our study cohorts consisting of patients undergoing pancreatic surgery or participating in biobanking and early detection. Analysis of online survey results revealed that given the hypothetical situation of being diagnosed with a pancreatic cyst or pancreatic cancer, the vast majority of respondents (>90%) would agree to undergo surveillance or surgery, respectively, regardless of race. Only a minority (3-12%) acknowledged any significant transportation, financial, or emotional barriers that would impact a decision to undergo surveillance or surgery. This suggests that the observed racial disparities may be due in part to the existence of other barriers that lie upstream of this decision point. CONCLUSION: Racial disparities exist not only for pancreatic cancer but also at earlier points along the continuum of care such as prevention and early detection. To our knowledge, this is the first study to document racial disparity in the management of patients with pancreatic cysts who are at risk of developing pancreatic cancer. Our results suggest that improving access to information and care for such at-risk individuals may lead to more equitable outcomes.

Total Pancreatectomy with Percutaneous Islet Autotransplant after Remote Islet Processing: A Viable Paradigm?

OBJECTIVES: Total pancreatectomy with islet autotransplant (TPIAT) is important therapy for select chronic pancreatitis (CP) patients. The specialized technique of islet isolation limits widespread TPIAT use. We hypothesized that remote islet isolation provides satisfactory islet yield and perioperative outcomes. METHODS: Retrospective review of TPIAT patients between 2020 and 2022. Islet isolation was performed off-site, with percutaneous intraportal islet autotransplant (IAT) completed the morning following pancreatectomy. Demographics and perioperative outcomes were analyzed. RESULTS: Fourteen patients underwent TPIAT; median age was 43 [interquartile range 12.5] years. Operation occurred 7.5 [14.8] years after pancreatitis diagnosis. The most common pancreatitis etiology was genetic (50%). All patients underwent preoperative endoscopic therapy; three underwent prior pancreatectomy. Operative time was 236 [51] minutes; subsequent percutaneous IAT time was 87 [35] minutes. The islet equivalent (IEQ)/kilogram (kg) yield was 3,456 [3,815] IEQ/kg. Nine patients had positive islet cultures. Two thromboembolic events and one bacteremia occurred. One perihepatic hematoma occurred after percutaneous portal venous access. Median postoperative length of stay was 14.5 days, and five patients (36%) were readmitted within 90 days. All patients were discharged home on insulin. No mortality occurred. CONCLUSION: Total pancreatectomy with remote islet isolation provides excellent islet yield for autotransplant and satisfactory perioperative outcomes.

Patients with deleterious germline mutations: A heterogeneous population for pancreatic cancer screening?

BACKGROUND AND OBJECTIVES: Modest data exist on the benefits of screening and surveillance for pancreatic cancer (PC) in high-risk individuals. Intraductal papillary mucinous neoplasms (IPMN) are known precursors to PC. We hypothesized that patients with high-risk deleterious germline mutations have a higher prevalence of IPMN. METHODS: All patients undergoing prospective screening at a single institution from 2013 to 2019 were reviewed. RESULTS: Of 1166 patients screened, 358 (31%) possessed germline mutations and/or family history of PC (mutations n = 201/358, 56%, family history n = 226/358, 63%) (median follow-up 2.7 years). IPMN was found in 127 patients (35.5%). The prevalence of IPMN in mutation carriers (18%) was higher than in the general population (p < 0.01). Germline mutation was an independent predictor of IPMN (odds ratio [OR] = 3.2; p < 0.01), while family history was not (p = 0.22). IPMN prevalence was distributed unevenly between mutation types (67%-Peutz-Jeghers; 43%-HNPCC, 24%-BRCA2; 17%-ATM; 9%-BRCA1; 0%-CDKN2A and PALB2). CONCLUSION: In this series, 18% of mutation carriers harbored IPMN, higher than the general population. Germline mutation, but not a family history of PC, was independently associated with IPMN. This prevalence varied across mutation subtypes, suggesting not all mutation carriers develop precancerous lesions. Genetic testing for patients with a positive family history may improve screening modalities for this high-risk population.

Neoadjuvant therapy at local versus outside institutions does not adversely impact surgical timing or long-term outcomes in patients with pancreatic adenocarcinoma.

BACKGROUND: Although high-volume centers are known to have better surgical outcomes, patients with pancreatic adenocarcinoma often receive chemotherapy at treatment centers closer to home. This study aimed to determine whether treatment site of neoadjuvant therapy relative to surgery location impacts surgical timing and long-term outcomes. METHODS: All patients with pancreatic adenocarcinoma who underwent oncologic resection at a single, high-volume institution between January 2016 and February 2020 and had neoadjuvant chemotherapy before surgery were queried from a prospectively maintained database. Patients were sorted based on location of neoadjuvant chemotherapy. RESULTS: A total of 179 patients were included in the study. Seventy-four (41.3%) patients received neoadjuvant chemotherapy at the same institution as their surgery (group A), 20 (11.2%) received chemotherapy outside of their surgical institution but within the same hospital/healthcare system (group B), and 85 (47.5%) received chemotherapy at an outside location (group C). The time from completion of neoadjuvant therapy to surgery was not significantly different between groups (A vs B vs C median [interquartile range]: 34.5 [14] vs 41.5 [24] vs 36 [22] days, P = .08). Thirty-day readmission rate was lower in group A (n (%): 1 (1.4%) vs 2 (10.0%) vs 11 (12.9%), P = .02). However, the 90-day mortality and overall survival did not differ significantly between groups. CONCLUSION: Patients may receive neoadjuvant therapy at local centers without impacting surgical scheduling. Although these patients may experience higher postoperative readmission rates, perioperative mortality and long-term survival are not adversely affected by location of chemotherapy. Multidisciplinary care can be effectively practiced in different locations without affecting overall outcomes in patients with pancreatic adenocarcinoma.

Portal Vein Thrombosis After Venous Reconstruction During Pancreatectomy: Timing and Risks.

BACKGROUND: Numerous studies have shown that portal vein resection during pancreatectomy can help achieve complete tumor clearance and long term-survival. While the safety of vascular resection during pancreatectomy is well documented, the risk of superior mesenteric vein/portal vein (SMV/PV) thrombosis after reconstruction remains unclear. This study aimed to describe the incidence and risk factors of SMV/PV thrombosis after vein reconstruction during pancreatectomy. METHODS: All patients who underwent portal vein resection (PVR) during pancreatectomy (2007-2019) were identified from a single institution prospective clinical database. Demographic and clinical data, operative and pathological findings, and postoperative outcomes were analyzed. RESULTS: Pancreatectomy with PVR was performed in 220 patients (mean age 65.1 years, male/female ratio 0.96). Thrombosis occurred in 36 (16.4%) patients after a median of 15.5 days [IQR 38.5, 1-786 days]. SMV/PV patency rates were 92.7% and 88.7% at 1 and 3 months, respectively. The rate of SMV/PV thrombosis varied according to SMV/PV reconstruction technique: 12.8% after venorrhaphy, 13.2% end-to-end anastomosis, 22.6% autologous vein, and 83.3% synthetic graft interposition (p < 0.0001). SMV/PV thrombosis was associated with increased 90-day mortality (16.7% vs 4.9%, p = 0.02) and overall 30-day complication rate (69.4% vs 42.9%, p = 0.006). Pancreatectomy type, neoadjuvant chemoradiation, pathologic tumor venous invasion, resection margin status, and manner of perioperative anticoagulation did not influence the incidence of PV thrombosis. SMV/PV thrombosis was associated with a nearly 5-times increased risk of postoperative sepsis after pancreatectomy. CONCLUSION: Portal vein thrombosis developed in 16% of patients who underwent pancreatectomy with PVR at a median of 15 days. PVR with synthetic interposition graft carries the highest risk for thrombosis.

Colon Involvement in Necrotizing Pancreatitis: Incidence, Risk Factors, and Outcomes.

OBJECTIVE: To investigate the incidence, risk factors, and outcomes of colon involvement in patients with necrotizing pancreatitis. SUMMARY/BACKGROUND DATA: Necrotizing pancreatitis is characterized by a profound inflammatory response with local and systemic implications. Mesocolic involvement can compromise colonic blood supply leading to ischemic complications; however, few data exist regarding this problem. We hypothesized that the development of colon involvement in necrotizing pancreatitis (NP) negatively affects morbidity and mortality. METHODS: Six hundred forty-seven NP patients treated between 2005 and 2017 were retrospectively reviewed to identify patients with colon complications, including ischemia, perforation, fistula, stricture/obstruction, and fulminant Clostridium difficile colitis. Clinical characteristics were analyzed to identify risk factors and effect of colon involvement on morbidity and mortality. RESULTS: Colon involvement was seen in 11% (69/647) of NP patients. Ischemia was the most common pathology (n = 29) followed by perforation (n = 18), fistula (n = 12), inflammatory stricture (n = 7), and fulminant C difficile colitis (n = 3). Statistically significant risk factors for developing colon pathology include tobacco use (odds ratio (OR), 2.0; 95% confidence interval (CI), 1.2-3.4, P = 0.009), coronary artery disease (OR, 1.9; 95% CI, 1.1-3.7; P = 0.04), and respiratory failure (OR, 4.7; 95% CI, 1.1-26.3; P = 0.049). When compared with patients without colon involvement, NP patients with colon involvement had significantly increased overall morbidity (86% vs 96%, P = 0.03) and mortality (8% vs 19%, P = 0.002). CONCLUSION: Colon involvement in necrotizing pancreatitis is common; clinical deterioration should prompt its evaluation. Risk factors include tobacco use, coronary artery disease, and respiratory failure. Colon involvement in necrotizing pancreatitis is associated with substantial morbidity and mortality.

Hypercalcemic Crisis Caused by a Parathyroid Mass Requiring Thoracoscopic Resection.

OBJECTIVE: To describe the presentation, work up, and treatment of a giant parathyroid adenoma presenting as hypercalcemic crisis that ultimately weighed 57 g and extended into the mediastinum, requiring hand-assisted thoracoscopic resection. METHODS: The patient is a 68-year-old man with a prior history of parathyroidectomy, who initially presented with a severe hypercalcemia of 16.3 mg/dL and a parathyroid hormone (PTH) level of 2692 pg/mL on routine labs. RESULTS: Diagnostic and staging work up revealed a 7.2-cm mass extending from just superior to the sternal notch into the right posterior mediastinum to the carina, causing esophageal displacement. No evidence of local invasion or distant metastasis was observed on further imaging, and cytology demonstrated hypercellular parathyroid tissue. The PTH level of the aspirate was >5000 pg/mL. The patient subsequently underwent a right hand-assisted video-assisted thoracoscopic resection of the intrathoracic mass. Final pathology identified a 7.0-cm, 57-g parathyroid adenoma, without any pathologic findings suspicious for malignancy. However, the endocrine surgery team plans for annual laboratory assessment to ensure no recurrence. CONCLUSION: Primary hyperparathyroidism is most commonly caused by a single adenoma. However, in the setting of severe hypercalcemia and elevated PTH, one must have a high suspicion for malignancy, and care should be taken to remove the mass en bloc. For extremely large adenomas extending into the mediastinum, a minimally invasive, hand-assisted, thoracoscopic approach is a safe and effective method of resection.

The continuum of complications in survivors of necrotizing pancreatitis.

BACKGROUND: Necrotizing pancreatitis survivors develop complications beyond infected necrosis that often require invasive intervention. Remarkably few data have cataloged these late complications after acute necrotizing pancreatitis resolution. We sought to identify the types and incidence of complications after necrotizing pancreatitis. DESIGN: An observational study was performed evaluating 647 patients with necrotizing pancreatitis captured in a single-institution database between 2005 and 2017 at a tertiary care hospital. Retrospective review and analysis of newly diagnosed conditions attributable to necrotizing pancreatitis was performed. Exclusion criteria included the following: death before disease resolution (n = 57, 9%) and patients lost to follow-up (n = 12, 2%). RESULTS: A total of 578 patients were followed for a median of 46 months (range, 8 months to 15 y) after necrotizing pancreatitis. In 489 (85%) patients 1 or more complications developed and included symptomatic disconnected pancreatic duct syndrome (285 of 578, 49%), splanchnic vein thrombosis (257 of 572, 45%), new endocrine insufficiency (195 of 549, 35%), new exocrine insufficiency (108 of 571, 19%), symptomatic chronic pancreatitis (93 of 571, 16%), incisional hernia (89 of 420, 21%), biliary stricture (90 of 576, 16%), chronic pain (44 of 575, 8%), gastrointestinal fistula (44 of 578, 8%), pancreatic duct stricture (30 of 578, 5%), and duodenal stricture (28 of 578, 5%). During the follow-up period, a total of 340 (59%) patients required an invasive intervention after necrotizing pancreatitis resolution. Invasive pancreatobiliary intervention was required in 230 (40%) patients. CONCLUSION: Late complications are common in necrotizing pancreatitis survivors. A broad variety of problems manifest themselves after resolution of the acute disease process and often require invasive intervention. Necrotizing pancreatitis patients should be followed lifelong by experienced clinicians.

Operative pancreatic debridement: Contemporary outcomes in changing times.

BACKGROUND/OBJECTIVES: Operative pancreatic debridement (OPD) is the historic gold standard for treating necrotizing pancreatitis (NP). Recent success with minimally invasive NP treatment approaches have raised the question of which NP patients require OPD. We therefore sought to define contemporary outcomes of NP patients undergoing OPD. METHODS: A retrospective analysis was performed of 116 consecutive NP patients undergoing OPD using a prospectively maintained institutional NP database between 2006 and 2018. RESULTS: 86 (74%) patients underwent open pancreatic debridement (OD) and 30 (26%) underwent open transgastric debridement (TGD). Median follow-up was 16 months (interquartile range [IQR], 8-45 months). Median age was 51 years (IQR, 43-65 years); 73 (63%) were male. Pancreatitis etiology included biliary (53%), alcohol (22%), and idiopathic/other (25%). Median time from diagnosis to OPD was 64.5 days (IQR, 32-114.5 days). Mean APACHE-II score was: admission 8.5 (standard deviation [SD], 5.9); worst 12.6 (SD, 7.9); preoperatively 7.2 (SD, 4.6). 40 patients (34%) were initially managed with minimally invasive techniques (percutaneous drain only in 24, endoscopic only in 6, combination in 10). Median postoperative length of stay was 11 days (IQR, 7-19 days). 90-day morbidity and mortality were 70% and 2%, respectively. CONCLUSIONS: NP patients who require OPD are critically and chronically ill. OPD is associated with substantial morbidity, but acceptable mortality in an experienced center with multidisciplinary support. This large contemporary series demonstrates that in properly selected patients, OPD remains an important treatment for NP.

Visceral artery pseudoaneurysm in necrotizing pancreatitis: incidence and outcomes.

Background: Visceral artery pseudoaneurysms (VA-PSA) occur in necrotizing pancreatitis; however, little is known about their natural history. This study sought to evaluate the incidence and outcomes of VA-PSA in a large cohort of patients with necrotizing pancreatitis. Methods: Data for patients with necrotizing pancreatitis who were treated between 2005 and 2017 at Indiana University Health University Hospital and who developed a VA-PSA were reviewed to assess incidence, presentation, treatment and outcomes. Results: Twenty-eight of 647 patients with necrotizing pancreatitis (4.3%) developed a VA-PSA between 2005 and 2017. The artery most commonly involved was the splenic artery (36%), followed by the gastroduodenal artery (24%). The most common presenting symptom was bloody drain output (32%), followed by incidental computed tomographic findings (21%). The median time from onset of necrotizing pancreatitis to diagnosis of a VA-PSA was 63.5 days (range 1-957 d). Twenty-five of the 28 patients who developed VA-PSA (89%) were successfully treated with percutaneous angioembolization. Three patients (11%) required surgery: 1 patient rebled following embolization and required operative management, and 2 underwent upfront operative management. The mortality rate attributable to hemorrhage from a VA-PSA in the setting of necrotizing pancreatitis was 14% (4 of 28 patients). Conclusion: In this study, VA-PSA occurred in 4.3% of patients with necrotizing pancreatitis. Percutaneous angioembolization effectively treated most cases; however, mortality from VA-PSA was high (14%). A high degree of clinical suspicion remains critical for early diagnosis of this potentially fatal problem.

Contexte: Les faux anévrismes des artères viscérales (FAAV) surviennent en présence d'une pancréatite nécrosante; on en sait cependant peu sur leur histoire naturelle. L'objectif de l'étude était d'évaluer l'incidence et les issues des FAAV dans une grande cohorte de patients atteints de pancréatite nécrosante. Méthodes: Nous avons examiné les données des patients atteints de pancréatite nécrosante traités entre 2005 et 2017 à l'Hôpital universitaire de l'Université de l'Indiana qui ont fait un FAAV afin d'évaluer l'incidence, les premiers signes, le traitement et les issues de cette affection. Résultats: Vingt-huit (4,3 %) des 647 patients atteints de pancréatite nécrosante inclus (2005­2017) ont fait un FAAV. L'artère la plus souvent touchée était l'artère splénique (36 %), suivie de l'artère gastroduodénale (24 %). Les premiers signes les plus courants étaient la présence de sang dans les liquides évacués par drainage (32 %), puis les résultats d'une tomodensitométrie effectuée pour une autre raison (21 %). Le délai médian entre l'apparition de la pancréatite nécrosante et le diagnostic de FAAV était de 63,5 jours (intervalle : 1 à 957 jours). Vingt-cinq des 28 patients ayant fait un FAAV (89 %) ont été traités avec succès par angioembolisation percutanée. Trois patients (11 %) ont dû être opérés : 2 dès le début, et le troisième parce qu'il a recommencé à saigner après l'embolisation. Le taux de mortalité par hémorragie due à un FAAV chez les personnes atteintes d'une pancréatite nécrosante était de 14 % (4 patients sur 28). Conclusion: Dans cette étude, 4,3 % des patients atteints de pancréatite nécrosante ont connu un FAAV. L'angioembolisation percutanée s'est avérée efficace dans la plupart des cas; cependant, la mortalité associée aux FAAV était élevée (14 %). Il est crucial de faire preuve d'une grande suspicion clinique afin de diagnostiquer tôt cette affection potentiellement mortelle.

Disconnected pancreatic duct syndrome predicts failure of percutaneous therapy in necrotizing pancreatitis.

BACKGROUND/OBJECTIVES: Minimally invasive approaches, such as percutaneous drainage (PD), are increasingly utilized as initial treatment in necrotizing pancreatitis (NP) requiring intervention. Predictors of success of PD as definitive treatment are lacking. Our aim was to assess the application, predictors of success, and natural history of PD in NP. We hypothesized that necrosis morphology patterns and disconnected pancreatic duct syndrome (DPDS) may predict the ability of PD to provide definitive therapy. METHODS: 714 NP patients were treated from 2005 to 2018. Patients achieving disease resolution with PD alone (PD) were compared to those requiring an escalation in intervention (Step). Outcomes were compared between groups using independent samples t-test, Fisher's exact test, and Pearson's correlation, as appropriate. P < 0.05 was accepted as statistically significant. RESULTS: 115 patients were initially managed with PD (42 PD, 73 Step). No difference in necrosis morphology was seen between the two groups. The PD group underwent significantly more repeat percutaneous interventions (PD, 3.2; Step, 2.0; P = 0.0006) including additional drain placement and drain upsize/reposition procedures. Patients with DPDS were more likely to require an escalation in intervention (odds ratio, 3.4; 95% confidence interval, 1.5-7.6; P = 0.003). The mean number of months to NP resolution was similar (PD, 5.7; Step, 5.8; P = 0.9). Mortality was similar (PD, 7%; Step 14%, P = 0.3). CONCLUSIONS: Necrosis morphology in and of itself does not reliably predict successful definitive treatment by percutaneous drainage. However, patients with disconnected pancreatic duct syndrome were less likely to have definitive resolution with PD alone.

Preoperative imaging characteristics predict poor survival and inadequate resection for left-sided pancreatic adenocarcinoma: a multi-institutional analysis.

BACKGROUND: Optimal treatment of pancreatic ductal adenocarcinoma of the neck, body and tail (PDAC-NBT) necessitates R0 surgical resection. Preoperative radiographic identification of patients likely to achieve successful oncologic resection remains difficult. This study seeks to identify preoperative imaging characteristics predictive of non-R0 resections or impaired survival for PDAC-NBT. METHODS: Patients at five high-volume centers who underwent resection for PDAC-NBT were retrospectively analyzed. The most immediate preoperative cross-sectional scan was assessed along with outcome measures of overall survival and margin status. RESULTS: 330 patients were treated between 2001 and 2016. Margin status included 247 R0 (78.2%), 67 R1 (21.2%), and 2 R2 (0.6%). A non-R0 resection predicted worse survival (p = 0.0002). On preoperative imaging, patients with tumors greater than 20 mm, tumor attenuation greater than 70 Hounsfield units, or who demonstrated pancreatic atrophy and/or calcifications also had worse survival (p = 0.010, p = 0.036, p = 0.025 respectively). Patients with tumors interfacing with the splenic artery or vein or extending posteriorly achieved fewer R0 resections (p = 0.0006, p = 0.0004, p = 0.001, respectively). CONCLUSION: Preoperative cross-sectional imaging can identify tumor characteristics associated with poor survival and non-R0 resection. Further investigation is needed to identify the appropriate surgical and treatment modifications necessary to clinically benefit this subset of patients.

Disconnected Pancreatic Duct Syndrome: Spectrum of Operative Management.

BACKGROUND: Disconnected pancreatic duct syndrome (DPDS) is common after necrotizing pancreatitis (NP). Surgical management may be by internal drainage or left (distal) pancreatectomy. Therapeutic decision-making must consider sinistral portal hypertension, parenchymal volume of disconnected pancreas, and timing relative to definitive management of pancreatic necrosis. The aim of this study is to evaluate outcomes after operative management for DPDS. METHODS: All patients with NP undergoing an operation for DPDS were included in the study (2005-2017). Perioperative outcomes and long-term durability were evaluated. RESULTS: Among 647 patients with NP, 299 (46%) had DPDS. Operative management was required in 202/299 (68%) patients with DPDS. Median follow-up was 30 mo (2-165). Definitive operative therapy included internal drainage (n = 111) or resection (n = 91). Time from NP diagnosis to operation was 126 d (20 d to 81 mo). Overall morbidity was 46%. Postoperative length of stay was 7 d (2-97). Readmission was required in 39 patients (19%). Mortality was 2%. Repeat pancreatic intervention was required in 23 patients (11%) at a median of 15 mo (1-98). Repeat pancreatectomy was performed in nine patients and the remaining 14 patients were managed with endoscopic therapy. CONCLUSIONS: DPDS is a common and challenging consequence of NP. Appropriate operation is durable in nearly 90% of patients.

Therapeutic Use of Adipose-Derived Stromal Cells in a Murine Model of Acute Pancreatitis.

BACKGROUND: No specific therapy exists for acute pancreatitis (AP), and current treatment remains entirely supportive. Adipose stem cells (ASCs) have significant immunomodulatory and regenerative activities. We hypothesized that systemic administration of ASCs would mitigate inflammation in AP. METHODS: AP was induced in mice by 6 hourly intraperitoneal injections of cerulein. Twenty-four hours after AP induction, mice were randomized into four systemic treatment groups: sham group (no acute pancreatitis), vehicle, human ASCs, and human ASC-conditioned media. Mice were sacrificed at 48 h, and blood and organs were collected and analyzed. Pancreatic injury was quantified histologically using a published score (edema, inflammation, and necrosis). Pancreatic inflammation was also studied by immunohistochemistry and PCR. RESULTS: When using IV infusion of Hoechst-labeled ASCs, ASCs were found to localize to inflamed tissues: lungs and pancreas. Mice treated with ASCs had less severe AP, as shown by a significantly decreased histopathology score (edema, inflammation, and necrosis) (p = 0.001). ASCs infusion polarized pancreatic macrophages toward an anti-inflammatory M2 phenotype. ASC-conditioned media reduced pancreatic inflammation similarly to ASCs only, highlighting the importance of ASCs secreted factors in modulating inflammation. CONCLUSION: Intravenous delivery of human ASCs markedly reduces pancreatic inflammation in a murine model of AP ASCs which represent an effective therapy for AP.

Percutaneous Gastrostomy in Necrotizing Pancreatitis: Friend or Foe?

BACKGROUND: Enteral nutrition plays a central role in managing necrotizing pancreatitis (NP). Although the nasojejunal (NJ) route is widely used, percutaneous gastrostomy (PEG-J) is an alternative technique that is also applied commonly. We hypothesized that NJ and PEG-J had similar morbidity in the setting of NP. METHODS: All patients receiving preoperative enteral nutrition before surgical debridement for NP (2005-2015) were segregated into NJ or PEG-J. RESULTS: A total of 242 patients had complete data for analysis (155 men/87 women; median age 54 years; 47% biliary and 16% alcohol-related pancreatitis). NJ was used exclusively in 187 patients (77%); 25 patients (10%) were fed exclusively by PEG-J; the remaining 30 patients (13%) had NJ first, followed by PEG-J. Equal proportions of NJ and PEG-J patients reached enteral feeding goal (67% vs. 68%, p ≈ 1) and increased serum albumin (39% vs. 36%, p = 0.87). No difference was seen in rate of pancreatic necrosis infection (NJ 53% vs. PEG-J 49%, p = 0.64). NJ patients had significantly more complications compared to PEG-J (51%vs.27%,p = 0.0015). However, NJ patients had more grade I/II complication, compared to PEG-J patients, who had more grade III/IV complication (Grade I/II: NJ 51%vs. PEG-J 16%; Grade III/IV NJ 0%vs. PEG-J 11%, p < 0.0001). CONCLUSION: In necrotizing pancreatitis, NJ and PEG-J both delivered enteral nutrition effectively. Patients with NJ feeding had significantly more complications than those with PEG-J; however, NJ complications were less severe.

Multifocal High-Grade Pancreatic Precursor Lesions: A Case Series and Management Recommendations.

Background: The risk of developing invasive cancer in the remnant pancreas after resection of multifocal high-grade pancreatic precursor lesions is not well known. We report three patients who were followed up after resection of multifocal high-grade pancreatic intraepithelial neoplasia (PanIN)-3 or intraductal papillary mucinous neoplasia (IPMN), two of whom eventually developed invasive carcinoma. Presentation: 1) 68-year-old woman who had a laparoscopic distal pancreatectomy for multifocal mixed-type IPMN, identified as high-grade on final pathology, with negative surgical margins. During semiannual monitoring, eight years from the first surgery, the patient developed suspicious features prompting surgical resection of the body with final pathology revealing invasive ductal adenocarcinoma in the setting of IPMN. 2) 48-year-old woman who had a distal pancreatectomy for severe acute/chronic symptomatic pancreatitis, with final pathology revealing multifocal high-grade PanIN-3, with negative surgical margins. Despite semiannual monitoring, two years from the first surgery, the patient developed pancreatic adenocarcinoma with liver metastasis. 3) 55-year-old woman who had a Whipple procedure for symptomatic chronic pancreatitis, with multifocal PanIN-3 on final pathology. The patient underwent completion pancreatectomy due to symptomatology and her high-risk profile, with final pathology confirming multifocal PanIN-3. Conclusion: Multifocal high-grade dysplastic lesions of the pancreas might benefit from surgical resection.

Venous Thromboembolism in Necrotizing Pancreatitis: an Underappreciated Risk.

BACKGROUND: Necrotizing pancreatitis (NP) is a severe systemic inflammatory process. We have observed a high incidence of venous thromboembolism (VTE) in NP patients. However, remarkably few data exist to document the true incidence of VTE-including splanchnic vein thrombosis (SVT), extremity deep venous thrombosis (eDVT), and pulmonary embolism (PE)-in NP. Therefore, we sought to determine the incidence and risk factors for VTE in NP patients. METHODS: Retrospective review of all NP patients treated at a single academic center between 2005 and 2015. VTE diagnosis was confirmed by ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and/or ventilation/perfusion (V/Q) scan. Descriptive statistics and univariate analysis were applied where appropriate; p value < 0.05 was considered statistically significant. RESULTS: Five hundred and forty-five NP patients (median age 53 years; 65% males) were reviewed. VTE was diagnosed in 312 patients (57%). SVT was found in 50%, eDVT in 16%, and PE in 6%. VTE in multiple sites was found in 22% of patients. VTE was diagnosed a median of 37 days following pancreatitis diagnosis. Seventy-nine percent of patients required at least one surgical procedure over the course of their NP. Patients requiring surgery had a DVT incidence of 58%; however, VTE was diagnosed preoperatively in 63%. Male gender, history of previous DVT, infected necrosis, development of organ failure, and development of respiratory failure were identified as risk factors for VTE (p = 0.001-0.04) by univariate analysis. CONCLUSIONS: Venous thromboembolism is extremely common in necrotizing pancreatitis. Regular ultrasound screening may be considered to facilitate early diagnosis in this extremely high-risk population.

Cystic pancreatic neuroendocrine tumors: A more favorable lesion?

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are predominantly solid lesions with malignant potential. Cystic PNETs are a small subset in which data are scarce. The aim of this study was to compare clinical and biologic differences between cystic and solid PNETs. METHODS: Patients with PNETs undergoing pancreatectomy between 1988 and 2016 at a high-volume center were reviewed retrospectively. Demographic, clinical, and histopathologic data were collected and analyzed. RESULTS: 347 patients with PNETs were identified; 27% (n = 91) were cystic. Patients with cystic PNETs were generally older (59 vs. 55 years, p = 0.05). Cystic PNETs were more commonly non-functional (95% vs. 82%, p = 0.004), asymptomatic (44% vs. 28%, p = 0.009), and located in the pancreatic body/tail (81% vs. 60%, p < 0.001) than solid PNETs. Although cystic and solid PNETs had similar sizes and pathologic stage at the time of resection, Ki-67 proliferation index (Ki-67 ≤ 9%: 98% vs. 85%; p = 0.007), and histologic grade (grade I: 84% vs. 59%; p = 0.009) had less aggressive features in cystic PNETs. CONCLUSION: In addition to reporting a higher than previously published incidence of cystic PNET (27%), this study found significant differences in multiple clinicopathologic variables between cystic and solid PNETs. Cystic PNET may be a distinct and possibly less aggressive subtype of PNET yet have similar pathologic stage, recurrence, and survival to solid PNETs. Cystic PNETs require further attention to better understand the true natural history.

High Rates of Readmission in Necrotizing Pancreatitis: Natural History or Opportunity for Improvement?

BACKGROUND: Necrotizing pancreatitis (NP) is a complex and heterogeneous disease with a protracted disease course. Hospital readmission is extremely common; however, few data exist regarding the cause of readmission in NP. METHODS: A retrospective review of NP patients treated between 2005 and 2017 identified patients readmitted both locally and to our hospital. All patients with unplanned hospital readmissions were evaluated to determine the cause for readmission. Clinical and demographic factors of all patients were recorded. As appropriate, two independent group t tests and Pearson's correlation or Fisher's exact tests were performed to analyze the relationship between index admission clinical factors and readmission. p values of < 0.05 were accepted as statistically significant. RESULTS: Six hundred one NP patients were reviewed. Median age was 52 years (13-96). Median index admission length of stay was 19 days (2-176). The most common etiology was biliary (49.9%) followed by alcohol (20.0%). Unplanned readmission occurred in 432 patients (72%) accounting for a total of 971 unique readmissions (mean readmissions/patient, 2.3). The most common readmission indications were symptomatic necrosis requiring supportive care and/or intervention (31.2%), infected necrosis requiring antibiotics and/or intervention (26.6%), failure to thrive (9.7%), and non-necrosis infection (6.6%). Patients requiring readmission had increased incidence of index admission renal failure (21.3% vs. 14.2%, p = 0.05) and cardiovascular failure (12.5% vs. 4.7%, p = 0.01). DISCUSSION: Readmission in NP is extremely common. Significant portions of readmissions are a result of the disease natural history; however, a percentage of readmissions appear to be preventable. Patients with organ failure are at increased risk for unplanned readmission and will benefit from close follow-up.