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.

Contemporary Outcomes of Transduodenal Sphincteroplasty: the Importance of Surgical Quality.

BACKGROUND: Sphincter of Oddi dysfunction (SOD) is managed primarily by endoscopic sphincterotomy (ES); however, surgical transduodenal sphincteroplasty (TDS) is a treatment option for select patients. In our high-volume pancreatico-biliary practice, we have observed variable outcomes among TDS patients; therefore, we sought to determine preoperative predictors of durable improvement in quality of life. METHODS: SOD patients treated by TDS between January 2006 and December 2015 were studied. The primary outcome measure was long-term changes in quality of life after sphincteroplasty. The secondary outcome measure examined postoperative outcomes, including postoperative complications, need for repeat procedures, and readmission rates. Perioperative data were abstracted, and the SF-36 quality-of-life (QoL) survey was administered. Standard statistical analysis included non-parametric methods to examine bivariate associations. RESULTS: Eighty-eight patients had an average follow-up duration of 6.7 (± 2.9) years. Thirty (34%) patients were naïve to endoscopic therapy. Patients with prior endoscopy averaged 2.1 procedures (range 1 to 13) prior to surgery. Perioperative morbidity was 27%; one postoperative death was caused by severe acute pancreatitis. Twenty-nine (33%) patients required subsequent biliary-pancreatic procedures. QoL analysis from available patients showed that 66% were improved or much improved. With multivariable analysis including SOD type and prior endoscopic instrumentation, freedom from surgical complication was the only variable that correlated significantly with a good outcome (p < 0.02). CONCLUSION: Surgical transduodenal sphincteroplasty provides durable symptom management for select patients with sphincter of Oddi dysfunction. Minimizing surgical complications optimizes long-term outcomes.

Do Weekend Discharges Impact Readmission Rate in Patients Undergoing Pancreatic Surgery?

BACKGROUND: Weekend readmissions have been previously associated with increased mortality after pancreatic resection, but the effect of weekend discharge is less understood. In this study, we aim to determine the impact of weekend discharges on 30-day readmission rate after pancreatic surgery. METHODS: All patients who underwent pancreatic surgery at a single, high-volume institution between 2013 and 2021 were retrospectively reviewed from a targeted, institutional ACS-NSQIP database. Patients who died prior to discharge were excluded. Multivariable logistic regression was used to assess the relationship between readmission and weekend discharge. RESULTS: Out of 2042 patients who underwent pancreatectomy, 418 patients (20.5%) were discharged on the weekend. Weekend discharge was associated with fewer Whipple surgeries, fewer open surgical approaches, and shorter operative time. Patients discharged on the weekend were also less likely to have had postoperative complications such as delayed gastric emptying (DGE) (6.7% vs 12.6%, p < 0.01) and were more frequently discharged to home (91.1% vs. 85.3%, p < 0.01). Thirty-day readmission rate was almost identical between groups (14.8% vs 14.8%, p = 0.997). On multivariable analysis, 30-day readmission was independently associated with DGE (OR (95% CI): 3.48 (2.31-5.23), p < 0.01), postoperative pancreatic fistula (3.36 (2.34-4.83), p < 0.01), myocardial infarction, and perioperative blood transfusion, but not weekend discharge (1.02 (0.72-1.43), p = 0.93). Readmission rate also did not differ significantly when including Friday discharges in the weekend group (15.2% vs 14.6%, p = 0.72). CONCLUSIONS: With careful clinical decision making, patients may safely be discharged on the weekend after pancreatic surgery without increasing 30-day readmission rate.

Transduodenal Sphincteroplasty: A Visual Case Study.

BACKGROUND: Sphincter of Oddi dysfunction is a challenging and rare clinical entity resulting in pancreatobiliary pain and stasis of bile and pancreatic juice. This problem was classically treated with surgical therapy, but as classification of the disease has changed and newer methods of endoscopic evaluation and therapy have evolved, operative transduodenal sphincteroplasty is now generally reserved as a final therapeutic option for these patients. In this video and manuscript, we describe our approach to operative transduodenal sphincteroplasty in a patient with type I Sphincter of Oddi dysfunction. METHODS: A 50-year-old female with history of Roux-en-Y gastric bypass presented with episodic right-upper-quadrant and epigastric abdominal pain with associated documented elevations in liver chemistries. Preoperative cross-sectional imaging demonstrated dilation of her common bile duct. After multidisciplinary discussion, the decision was made to pursue operative transduodenal sphincteroplasty. RESULTS: All key operative steps of the transduodenal sphincteroplasty are demonstrated in the embedded video. Key operative steps include laparotomy, generous Kocher maneuver, and duodenotomy over the ampulla, allowing access for sequential biliary and pancreatic sphincterotomies and sphincteroplasties with absorbable suture. The duodenotomy and abdominal fascia are then closed. Our patient underwent sequential diet advancement and was discharged to home on postoperative day five. At clinic follow-up, pancreatobiliary-type pain had resolved. CONCLUSION: The embedded video demonstrates a case of operative transduodenal sphincteroplasty, which can provide durable results in appropriate patient populations.

Transgastric pancreatic necrosectomy: Tricks of the trade.

Necrotizing pancreatitis (NP) affects 20 % of the 300,000 patients diagnosed with acute pancreatitis every year. Mechanical intervention to debride necrotic and/or infected pancreatic and peripancreatic tissue is frequently required. Minimally invasive approaches to treat pancreatic necrosis have gained popularity over the last two decades, including transgastric pancreatic necrosectomy. The purpose of this report is to review the indications, surgical technique, advantages, and limitations of surgical transgastric necrosectomy.

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.

Management of Necrotizing Pancreatitis.

Necrotizing pancreatitis affects 10% to 15% of all patients with acute pancreatitis. Despite improved understanding of this complex disease, it is still attended by up to 15% mortality. Necrotizing pancreatitis provides the clinical challenges of working in a multi-disciplinary group, determining proper timing for intervention, and identifying appropriate intervention approaches. The step-up approach consists of supportive care initially. When there is documented infected necrosis, treatment begins with antibiotics, progressing to minimally invasive mechanical necrosis intervention, and reserving surgery as the final treatment modality. However, treatment must be tailored to the individual patient. This article provides an overview of necrotizing pancreatitis.

Pancreatitis associated anxiety, depression, and stress: Hypothesis, definition, and intervention.

Necrotizing pancreatitis is characterized by a prolonged disease course requiring frequent hospitalization and intervention. Necrotizing pancreatitis patients have high rates of intensive care unit admission and organ failure. Critical illness is an identified risk factor for the development of anxiety, depression, and posttraumatic stress disorder. Limited literature examines quality of life in necrotizing pancreatitis patients, and studies examining psychiatric sequalae of necrotizing pancreatitis including depression, anxiety, and posttraumatic stress disorder are virtually nonexistent. Here, we review critical literature examining risk factors for poor mental health outcomes during and after necrotizing pancreatitis, identify several screening instruments to quantify mental health outcomes, and propose an intervention to improve mental health outcomes in patients with necrotizing pancreatitis. We conclude that establishing the incidence of mental health disorders and implementing strategies to improve mental health outcomes are critical to holistic care of necrotizing pancreatitis patients.

Obesity Worsens Local and Systemic Complications of Necrotizing Pancreatitis and Prolongs Disease Course.

BACKGROUND: Obesity is epidemic in the USA. Limited data exist examining obesity's influence on necrotizing pancreatitis (NP) disease course. METHODS: Retrospective review of prospectively maintained database of 571 adult necrotizing pancreatitis patients treated between 2007 and 2018. Patients were grouped according to body mass index (BMI) at disease onset. Patient characteristics, necrotizing pancreatitis course, and outcomes were compared between non-obese (BMI < 30) and obese (BMI > 30) patients. RESULTS: Among 536 patients with BMI data available, 304 (57%) were obese (BMI > 30), and 232 (43%) were non-obese (BMI < 30). NP etiology in the obese group was more commonly biliary (55% versus 46%, p = 0.04) or secondary to hypertriglyceridemia (10% versus 2%, p < 0.001) and less commonly alcohol (17% versus 26%, p = 0.01). Obese patients had a higher incidence of baseline comorbid disease. The CT severity index was similar between groups though obese patients had a higher rate of > 50% pancreatic gland necrosis (27% versus 19%, p = 0.02). The rates of infected necrosis and organ failure were higher among obese patients. Percutaneous drainage was more common in obese patients. Time to first necrosis intervention was earlier with increasing BMI. NP disease duration was longer in obese patients. The overall mortality rate of non-obese and obese patients did not differ. However, mortality rate increased with increasing BMI. CONCLUSION: Necrotizing pancreatitis in obese patients is characterized by a prolonged disease course, a higher risk of organ failure, infected necrosis, and the need for early necrosis-related intervention. Mortality increases with increasing BMI.

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.

Histopathologic correlation of pancreatic fibrosis with pancreatic magnetic resonance imaging quantitative metrics and Cambridge classification.

PURPOSE: To determine the correlation of the T1-weighted signal intensity ratio (T1 SIR, or T1 Score) and arterial-to-delayed venous enhancement ratio (ADV ratio) of the pancreas with pancreatic fibrosis on histopathology. METHODS: Sixty consecutive adult CP patients who had an MRI/MRCP study prior to pancreatic surgery were analyzed. Three blinded observers measured T1 SIR of pancreas to spleen (T1 SIR p/s), pancreas-to-paraspinal muscle (T1 SIR p/m), ADV ratio, and Cambridge grade. Histopathologic grades were given by a gastrointestinal pathologist using Ammann's fibrosis score. Statistical analysis included Spearman's correlation coefficient of the T1 SIR, ADV ratio, Cambridge grade with the fibrosis score, and weighted kappa for interobserver agreement. RESULTS: The study population included 31 female and 29 male patients, with an average age of 52.1 (26-78 years). Correlations between fibrosis score and T1 SIR p/s, T1 SIR p/m, and ADV ratio were ρ = - 0.54 (p = 0.0001), ρ = - 0.19 (p = 0.19), and ρ = - 0.39 (p = 0.003), respectively. The correlation of Cambridge grade with fibrosis score was ρ = 0.26 (p = 0.07). There was substantial interobserver agreement (weighted kappa) for T1 SIR p/s (0.78), T1 SIR p/m (0.71), and ADV ratio (0.64). T1 SIR p/s of ≤ 1.20 provided a sensitivity of 74% and specificity of 50% (AUC: 0.74), while ADV ratio of ≤ 1.10 provided a sensitivity of 75% and specificity of 55% (AUC: 0.68) to detect a fibrosis score of ≥ 6. CONCLUSION: There is a moderate negative correlation between the T1 Score (SIR p/s) and ADV ratio with pancreatic fibrosis and a substantial interobserver agreement. These parenchymal metrics show a higher correlation than the Cambridge grade.

Contemporary Intervention in Necrotizing Pancreatitis: Improved Understanding Changing Practice.

BACKGROUND: Treatment of necrotizing pancreatitis (NP) has shifted in favor of a minimally invasive step-up approach rather than early open pancreatic debridement. We hypothesized that this paradigm shift would be reflected in the intervention, morbidity, and mortality profile of NP patients. STUDY DESIGN: Single-institution retrospective review of 767 NP patients treated between 2005 and 2019. Two eras of NP intervention were identified relative to the introduction of a minimally invasive approach to NP. Patients treated between 2005 and 2010 were classified as the "early" group and compared with patients treated between 2011 and 2019, classified as the "late" group. RESULTS: In total, 299 NP patients comprised the early group and 468 patients comprised the late group. No differences were seen in patient demographics, comorbidity profile, or NP etiology between groups. Necrosis volume, necrosis location, CT severity index (CTSI), and rates of infected necrosis were similar between groups. No difference was seen in mortality. Mechanical intervention for NP was more common in the early than the late group (86% vs. 73%, p < 0.001). Time to first intervention was similar between groups (79 ± 7d vs. 75 ± 6d). The early group had higher rates of open pancreatic debridement (72% vs. 55%, p < 0.001). Endoscopic intervention was less common in the early than the late group (7% vs. 16%, p < 0.001). NP disease duration was longer in the early than the late group (223 ± 12d vs. 179 ± 7d, p = 0.001). CONCLUSION: Contemporary management of necrotizing pancreatitis is marked by less frequent operative debridement and shorter disease duration.

2021 SSAT Debate: Selective Approach to Resection of the Superior Mesenteric Artery in Pancreatic Cancer vs Superior Mesenteric Artery Encasement Is Not an Absolute Contraindication for Surgery in Pancreatic Cancer.

OVERVIEW: This manuscript summarizes an excellent debate from the 2021 SSAT/Pancreas Club symposium on arterial resection in pancreas cancer. Two world-recognized experts, Professor Ugo Boggi from Pisa, IT, and Dr. Mark Truty from the Mayo Clinic in Rochester, MN, offered their views on the role of arterial resection in locally advanced pancreas ductal adenocarcinoma. Both speakers have extensive experience pushing the technical envelope with extended vascular resection in pancreatectomy. However, both highlight important concepts of resectability extending well beyond technique: namely, patient global physiology, tumor biology, and response to chemotherapy. The debate was spirited, and this subsequent review is an excellent look at the status quo. N. J. Zyromski, MD, Indianpolis, IN, November, 2021.

Biliary Stricture After Necrotizing Pancreatitis: An Underappreciated Challenge.

OBJECTIVE: Biliary stricture in necrotizing pancreatitis (NP) has not been systematically categorized; therefore, we sought to define the incidence and natural history of biliary stricture caused by NP. SUMMARY OF BACKGROUND DATA: Benign biliary stricture occurs secondary to bile duct injury, anastomotic narrowing, or chronic inflammation and fibrosis. The profound locoregional inflammatory response of NP creates challenging biliary strictures. METHODS: NP patients treated between 2005 and 2019 were reviewed. Biliary stricture was identified on cholangiography as narrowing of the extrahepatic biliary tree to <75% of the diameter of the unaffected duct. Biliary stricture risk factors and outcomes were evaluated. RESULTS: Among 743 NP patients, 64 died, 13 were lost to follow-up; therefore, a total of 666 patients were included in the final cohort. Biliary stricture developed in 108 (16%) patients. Mean follow up was 3.5 ±â€Š3.3 years. Median time from NP onset to biliary stricture diagnosis was 4.2 months (interquartile range, 1.8 to 10.9). Presentation was commonly clinical or biochemical jaundice, n = 30 (28%) each. Risk factors for stricture development were splanchnic vein thrombosis and pancreatic head parenchymal necrosis. Median time to stricture resolution was 6.0 months after onset (2.8 to 9.8). A mean of 3.3 ±â€Š2.3 procedures were performed. Surgical intervention was required in 22 (20%) patients. Endoscopic treatment failed in 17% (17/99) of patients and was not associated with stricture length. Operative treatment of biliary stricture was more likely in patients with infected necrosis or NP disease duration ≥6 months. CONCLUSION: Biliary stricture occurs frequently after NP and is associated with splanchnic vein thrombosis and pancreatic head necrosis. Surgical correction was performed in 20%.

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.