Surgical Diagnoses of Pancreatic Adenocarcinoma Not Found on Previous Endoscopic Ultrasound: A Case Series and Review of the Literature.

INTRODUCTION: Pancreatic cancer is a leading cause of death in North America and Western Europe with rising rates in the developing world. Endoscopic ultrasound (EUS) with FNA (fine needle aspiration) is a critical component in the evaluation and diagnosis of pancreatic lesions with a high sensitivity and specificity. In this paper, we report patients at our center who eventually developed pancreatic cancer despite an early negative EUS, and identifying factors that may result in a missed diagnosis. METHODS: The University of Louisville database was queried for patients who had a Whipple procedure for presumed benign disease and had a pre-operative EUS between 2008 and 2018. Patients who had pancreatic adenocarcinoma on final pathology were identified. Demographic, clinical, EUS, operative, and pathologic details were reviewed for each case in efforts to identify factors associated with failure to diagnose a pancreatic malignancy on EUS. RESULTS: Five patients who had pancreatic adenocarcinoma on final pathology were reviewed in detail and their cases are presented in the paper. Four of the patients had dilation of the common bile duct, three had chronic pancreatitis. Two of them had previous surgery on the pancreas or bile ducts. CONCLUSIONS: All of the patients presented in the paper had variables that made their EUS evaluation challenging. A high index of suspicion must be maintained in patients that do not improve after appropriate treatment of their strictures or pancreatic lesions. In the future, new techniques, such as fine needle biopsy and biomarker assays, may improve diagnosis accuracy.

Impact of myopenia and myosteatosis in patients undergoing abdominal surgery for chronic pancreatitis.

BACKGROUND: Surgery for chronic pancreatitis is associated with major morbidity and mortality. The aim of this study is to examine the role of preoperative muscle volume and quality on postoperative outcomes in patients with chronic pancreatitis. METHODS: All patients who underwent abdominal surgery for chronic pancreatitis between 2011 and 2018 were identified from an institutional surgical database. Patient demographics, clinical indices, and perioperative computed tomography scans were collected. Myopenia and myosteatosis were measured at the L3 vertebral level. Regression analysis was used to identify risk factors for major complications (Clavien-Dindo ≥3a) and length of stay. RESULTS: Seventy-five patients were identified. Toxic-metabolic or obstructive causes were the main underlying etiologies. Thirty patients were myopenic (40%), and 36 patients were myosteatotic (48%). Sixteen patients (21%) had a major complication. Median length of stay was 10 days. Both myopenia and myosteatosis were associated with major complications (hazard ratio = 7.85, 95% confidence interval: 1.91-32.29, P = .004 and hazard ratio = 4.351, 95% confidence interval: 1.22-15.52, P = .023). Myosteatosis was associated with increased length of stay (parameter estimate = 0.297, 95% confidence interval: 0.012-0.583, P = .041). CONCLUSION: Myopenia and myosteatosis were common and significant risk factors for adverse postoperative events. Preoperative muscle assessment may help in the risk stratification of surgical patients and identify patients that require preoperative nutritional and physical optimization.

Management of complicated biliary disease in the pediatric population.

BACKGROUND: Cholesterol stones and biliary dyskinesia have replaced hemolytic disease as the primary indication for pediatric cholecystectomy. This study looks at the cohort of pediatric patients with complicated biliary disease, defined as choledocholithiasis and/or gallstone pancreatitis, to determine the incidence and best treatment options. METHODS: A retrospective review of all cholecystectomies performed over 15 years admitted to the surgical service at a single free-standing children's hospital was performed. Patient factors, indications for cholecystectomy, and final treatment were recorded. Complicated gallbladder disease was defined as having image-confirmed choledocholithiasis or gallstone pancreatitis. High-risk patients were those with imaging that demonstrated definitive choledocholithiasis or cholelithiasis with common bile duct enlargement. Low risk patients were those with cholelithiasis or gallbladder sludge on imaging combined with an elevated bilirubin and/or lipase. RESULTS: A total of 695 cholecystectomies were performed over the 15-year time period. Average patient age was 13.4 years. Of the 695 cholecystectomies, 457 were performed for stone disease (66%) (64 hemolytic) and 236 (34.0%) were performed for biliary dyskinesia. Hundred and three (14.8% of all cholecystectomies, 22.5% of those with stone disease) presented with choledocholithiasis and/or gallstone pancreatitis (complicated disease). In high-risk patients, 28/47 (59.6%) underwent endoscopic retrograde cholangiopancreatography/sphincterotomy. In low-risk patients (no choledocholithiasis or common duct enlargement), 13/56 (23.2%) required endoscopic retrograde cholangiopancreatography/sphincterotomy (P < .05). The indication for endoscopic retrograde cholangiopancreatography after cholecystectomy was choledocholithiasis and none of these patients had bile leak complications. CONCLUSION: The incidence of pediatric complicated biliary disease due to cholesterol stones is equal to that of adults. These data suggest that a patient with imaging evidence of choledocholithiasis or common bile duct enlargement may require endoscopic retrograde cholangiopancreatography, dependent on clinical course, and this should be strongly considered before cholecystectomy. Those without such radiographic findings can undergo laparoscopic cholecystectomy and have postoperative endoscopic retrograde cholangiopancreatography if needed.

Long-term Follow-up of Patients Undergoing Endoscopic Intervention for Abdominal Pain with Minimal Biliary Ductal Dilation, Stone Disease, or Malignancy.

BACKGROUND: Safety and efficacy of endoscopic methods in management of biliary colic after cholecystectomy in patients with minimal biliary ductal dilation and no evidence of biliary stones or malignancy have not been clearly demonstrated. This study aimed to assess the efficacy of endoscopic management of such patients. METHODS: The University of Louisville database was queried for patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for colicky abdominal pain between 1996 and 2016 who had a common bile duct (CBD) diameter of ≤12 mm. All patients had undergone prior cholecystectomy and were free of malignancy. Demographic, serologic, procedural, and outcome variables were assessed. RESULTS: A total of 35 patients underwent a total of 99 ERCPs. Median CBD diameter was 10 (range 4-12) mm. A total of 31 patients (89%) underwent sphincterotomy, 28 (80%) underwent stent placement, and 5 (14%) underwent balloon dilation. The median number of ERCPs performed was 2 (range 1-10). Three of the 35 patients (9%) developed post-ERCP pancreatitis at some point during their treatment. At last follow-up since initial ERCP (median 16 months, range 2.4-184 months), 12 (34%) patients endorsed abdominal pain and 11 (31%) reported experiencing nausea. CONCLUSION: For select patients with abdominal pain in the setting of minimal CBD dilation and no evidence of stone disease or malignancy, ERCP can safely and effectively be used to manage symptoms. While patients may require multiple interventions, they can derive long-term relief from these procedures.

Adverse outcomes and short-term cost implications of bile duct injury during cholecystectomy.

BACKGROUND: Bile duct injury (BDI) is an uncommon but major complication of cholecystectomy that has a poorly defined magnitude of effect on hospital costs. This study sought to calculate the healthcare costs, length of stay, and discharge status associated with bile duct injury in patients undergoing cholecystectomy in the United States. METHODS: The Premier Healthcare Database, which comprises hospital-billing records from over 700 hospitals in the United States, was queried for all patients undergoing cholecystectomy between January 2010 and March 2018. BDI was defined by ICD-9-CM and ICD-10-CM codes. Patient demographics, clinical characteristics, and operative information were extracted. Hospital costs, length of stay, and discharge status were compared between BDI and non-BDI patients. Propensity score matching was used to minimize confounding factors. Multivariable regression models were used to estimate the association between BDI and the outcomes variables. RESULTS: A total of 1,168,288 cholecystectomies were identified. BDI occurred in 878 patients (0.08%). Laparoscopy was the most common approach (> 95%). The majority of BDI occurred during inpatient admissions (71.0%). BDI patients had higher index admission hospital costs ($18,771 vs. $12,345, p < 0.0001), increased rate of discharge to an institutional post-acute care facility (odds ratio 3.89, 95% CI 2.92-5.19, p < 0.0001), and increased risk of readmission within 30 days after discharge (odds ratio 1.86, 95% CI 1.52-2.28, p < 0.0001), compared to patients without BDI. Among inpatient cholecystectomies, BDI was associated with increased length of stay (8.6 days vs. 4.8 days, p < 0.0001). CONCLUSION: BDI is associated with significantly increased hospital costs, length of stay, 30-day readmission, and discharge to an institutional post-acute care facility.

Safety, Efficacy, and Technical Details of Endoscopic Retrograde Cholangiopancreatography After Irreversible Electroporation for Locally Advanced Pancreatic Cancer.

BACKGROUND: Patients undergoing irreversible electroporation (IRE) for locally advanced pancreatic cancer (LAPC) may experience biliary obstruction owing to inflammation generated by tumor ablation. This study assessed the safety, efficacy, and technical details of endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression after IRE. METHODS: A single-institution database of patients undergoing IRE for LAPC between 2012 and 2017 was queried for patients requiring post-IRE ERCP. Patients were evaluated along demographic, laboratory, procedural, and outcome measures. RESULTS: Of 113 patients with LAPC who underwent IRE, 6 (5.3%) required subsequent ERCP for biliary obstruction. A total of 12 ERCPs were performed. Two patients (33%) had duodenal bulb narrowing requiring dilation, and one patient (17%) had a pancreatic head cyst complicating guidewire passage. Biliary cannulation was achieved in all patients in a median time of 30 min. Four patients (67%) underwent sphincterotomy, and 5 (83%) underwent stent placement. Post-procedurally, all showed liver test improvement. None developed pancreatitis. Four patients underwent a 2nd ERCP. All were successful and included stent placement. CONCLUSIONS: For patients with biliary obstruction after IRE, ERCP with sphincterotomy and stent placement can safely relieve this obstruction. Duodenal dilation and careful guidewire manipulation may be required to maximize technical success in these patients.

An unusual presentation of congenital superior mesenteric artery (SMA) syndrome.

A case of a 39-year-old woman diagnosed with superior mesenteric artery syndrome after a 25-year history of nausea, vomiting, and abdominal pain that began as a teenager and the absence of any significant weight loss illustrates the diagnostic complexity of this entity, particularly among teenagers and young adults who present with these symptoms. The patient underwent multiple upper endoscopies and serologic evaluations before a contrasted CT demonstrated an acutely angled SMA and duodenal compression, prompting the diagnosis of SMA syndrome. This case underscores the importance of including congenital SMA syndrome on the differential in young people without an obvious cause of persistent nausea, vomiting, and abdominal pain.

Ductal Cell Reprogramming to Insulin-Producing Beta-Like Cells as a Potential Beta Cell Replacement Source for Chronic Pancreatitis.

Islet cell auto-transplantation is a novel strategy for maintaining blood glucose levels and improving the quality of life in patients with chronic pancreatitis (CP). Despite the many recent advances associated with this therapy, obtaining a good yield of islet infusate still remains a pressing challenge. Reprogramming technology, by making use of the pancreatic exocrine compartment, can open the possibility of generating novel insulin-producing cells. Several lineage-tracing studies present evidence that exocrine cells undergo dedifferentiation into a progenitor-like state from which they can be manipulated to form insulin-producing cells. This review will present an overview of recent reports that demonstrate the potential of utilizing pancreatic ductal cells (PDCs) for reprogramming into insulin- producing cells, focusing on the recent advances and the conflicting views. A large pool of ductal cells is released along with islets during the human islet isolation process, but these cells are separated from the pure islets during the purification process. By identifying and improving existing ductal cell culture methods and developing a better understanding of mechanisms by which these cells can be manipulated to form hormone-producing islet-like cells, PDCs could prove to be a strong clinical tool in providing an alternative beta cell source, thus helping CP patients maintain their long-term glucose levels.

Safety and efficacy of irreversible electroporation in the treatment of obstructive jaundice in advanced hilar cholangiocarcinoma.

BACKGROUND: Irreversible electroporation (IRE) has successfully been used for palliation of pancreatic and liver cancers due to its ability to ablate tumors without destroying nearby vital structures. To date, it has not been evaluated in patients with advanced hilar cholangiocarcinoma (AHC). This study presents a single-institution experience with IRE for management of obstructive jaundice in AHC. METHODS: A single-institution database was queried for patients undergoing IRE for AHC after PTBD placement for relief of obstructive jaundice from 2010 to 2017 and compared to a control group treated with standard of care only (No IRE). RESULTS: Twenty-six patients underwent IRE for AHC after PTBD replacement. Three patients experienced complications, with two experiencing severe (≥ grade 3) complications. After IRE, median time to PTBD removal was 122 days (range 0-305 days) and median catheter-free time before requiring PTBD replacement was 305 days (range 92-458 days). In comparison, the 137 control patients had an admission rate of 59% (N = 80 patients) for PTBD infection, occlusion, or catheter related problem. CONCLUSION: IRE safely achieves biliary decompression via tumor electroporation and allows PTBD removal for an extended period of time. In appropriately selected patients with obstructive jaundice in the setting of AHC, IRE can be used to increase catheter-free days and optimize overall quality of life.

Correlation of Biliary Colic in the Absence of Cholelithiasis with Pancreaticobiliary Obstruction.

A small fraction of patients undergoing cholecystectomy for biliary colic are subsequently diagnosed with an obstructive pancreatic head mass. We review our experience with such patients to provide insight into improving evaluation before cholecystectomy. Retrospective chart review of patients undergoing cholecystectomy from 2004 to 2015 identified six patients who underwent laparoscopic cholecystectomy for biliary colic before being diagnosed with a pancreatic head neoplasm within six months after cholecystectomy. Charts were analyzed for presenting symptoms, evaluation before and after cholecystectomy, and operative findings. Patients ranged from 50 to 72 years of age and included five males and one female. None had evidence of cholelithiasis or acute cholecystitis on initial evaluation. Median time from cholecystectomy to diagnosis of pancreatic head mass was two months (range 1-5 months). Two patients eventually underwent pancreaticoduodenectomy. Patients with symptoms of biliary colic in the absence of evidence of cholecystitis or choledochal abnormality should undergo intraoperative cholangiogram at the time of cholecystectomy as well as close clinical follow-up to ensure resolution of symptoms. Abnormalities of either should prompt radiographic evaluation focused on identification of a pancreatic mass causing extrinsic compression of the bile duct.

Predictive risk factors associated with cholangitis following ERCP.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is used for the management of many pancreaticobiliary disorders. It is generally safe with a few short-term complications. The risk factors for the development of post-ERCP cholangitis due to stent occlusion have not been previously described. This study identified such risk factors among patients undergoing ERCP and stent placement for pancreatic or biliary obstruction. METHODS: 3648 ERCPs performed at the University of Louisville from 2008 to 2016 were reviewed. Data including patient demographics, diagnostic, laboratory, and ERCP related data were included. Patients were classified as having post-ERCP cholangitis if they developed jaundice, fever, right upper quadrant abdominal pain, and confirmatory findings of stent occlusion and/or purulent drainage at the time of repeat ERCP. These patients were compared to those who did not develop post-ERCP cholangitis using univariate and multivariate analyses. RESULTS: A total of 431 patients met inclusion criteria. Of these, 57 (13.2%) developed post-ERCP cholangitis. The average age of patients was 57 years with 57% women and 43% men. On univariate analysis, patients developing post-ERCP cholangitis were more likely to be of increased age, have higher white blood cell count (WBC), total bilirubin (TBili), AST, ALT, and alkaline phosphatase (AlkPhos), and a decreased serum albumin level. Risk factors for post-ERCP cholangitis due to stent occlusion identified on multivariate analysis include: a diagnosis of cancer, the placement of multiple biliary stents at index ERCP, and low serum albumin level. CONCLUSIONS: The development of post-ERCP cholangitis due to stent occlusion is strongly associated with the presence of malignancy, the placement of multiple biliary stents, and low serum albumin. A decreased threshold to monitor for stent occlusion, including routine liver function tests and prophylactic stent removal or exchange, should be employed in patients with these characteristics.

Assessing the value of endoscopic ultrasound in predicting symptom severity and long-term clinical course in chronic pancreatitis.

BACKGROUND: To date, no studies have evaluated the correlation between number of endoscopic ultrasound (EUS) criteria met for chronic pancreatitis (CP) and symptom severity over the course of the disease. This study assessed the relationship between number of EUS-based diagnostic criteria for CP and CP severity over time. METHODS: A University of Louisville database was queried for patients undergoing EUS due to concern for chronic pancreatitis between 2005 and 2016. Patients were grouped based on EUS criteria met for CP and groups were compared along outcome and procedural variables. RESULTS: Of a total of 243 patients, 24, 129, and 90 patients met 1-3, 4-5, and ≥6 EUS diagnostic criteria, respectively. Median follow-up time was 33 months. Along all follow-up parameters, number of diagnostic criteria was positively correlated with an increased percentage of patients requiring operative intervention for chronic pancreatitis on univariate and multivariate analysis. CONCLUSIONS: In addition to the role of EUS criteria in establishing the diagnostic severity of patients with symptomatic chronic pancreatitis, the number of EUS-based criteria may help predict patients who will eventually require operative intervention and thus prompt referral to a pancreatobiliary surgeon earlier in the course of a patient's disease.

Comparative Efficacy of Bilateral Thoracoscopic Splanchnicectomy for Intractable Pain Secondary to Pancreatic Cancer vs Chronic Pancreatitis.

BACKGROUND: Splanchnicectomy has been evaluated for treatment of chronic pain in both pancreatic cancer and chronic pancreatitis patients, although its efficacy has not been compared in these 2 patient populations. This study aimed to compare bilateral thoracoscopic splanchnicectomy in treatment of abdominal pain secondary with pancreatic cancer and chronic pancreatitis. STUDY DESIGN: A University of Louisville database was evaluated from July 1998 to March 2016 for patients undergoing bilateral thoracoscopic splanchnicectomy for intractable pain secondary to pancreatic cancer (n = 48) or chronic pancreatitis (n = 75). Patients were evaluated pre- and postoperatively with regard to abdominal pain and related symptoms, narcotic analgesic requirements, and hospital admissions. Narcotic use was quantified using the Kentucky All Schedule Prescription Electronic Reporting system. RESULTS: After bilateral thoracoscopic splanchnicectomy, 28% of pancreatic cancer patients continued to experience abdominal pain compared with 57% of chronic pancreatitis patients. Daily narcotic dose decreased for 74% of pancreatic cancer compared with 32% of chronic pancreatitis patients (p < 0.001). Sixty-seven percent of pancreatic cancer patients discontinued pain medications completely compared with 14% of chronic pancreatitis patients (p < 0.001). Hospitalizations decreased significantly in both groups (p < 0.001; p = 0.001), although mean number of postoperative hospitalizations was lower for pancreatic cancer (0.5) compared with chronic pancreatitis patients (2.80) (p < 0.001). Mean follow-up was significantly shorter for pancreatic cancer patients than for chronic pancreatitis patients (8 months vs 32 months; p < 0.001). CONCLUSIONS: Bilateral thoracoscopic splanchnicectomy safely, effectively, and durably relieves abdominal pain in patients with both pancreatic cancer and chronic pancreatitis. However, it is more effective in providing pain relief and preventing pain-related hospitalizations in patients with pancreatic cancer compared with those with chronic pancreatitis.

Endoscopic management of acute pancreatitis.

Patients presenting with acute pancreatitis can be complex on different levels. Having a multifaceted approach to these patients is often necessary with radiographic, endoscopic, and surgical modalities all working to benefit the patient. Major surgical intervention can often be avoided or augmented by therapeutic and diagnostic endoscopic maneuvers. The diagnostic role of endoscopy in patients presenting with acute idiopathic pancreatitis can help define specific causative factors and ameliorate symptoms by endoscopic maneuvers. Etiologies of an acute pancreatitis episode, such as choledocholithiasis with or without concomitant cholangitis, microlithiasis or biliary sludge, and anatomic anomalies, such as pancreas divisum and pancreatobiliary ductal anomalies, often improve after endoscopic therapy.

Evaluation and treatment of biliary leaks after gastrointestinal surgery.

INTRODUCTION: Since the introduction of laparoscopic cholecystectomy more than two decades ago, the incidence of bile duct injury has remained greater than that established during the era of open cholecystectomy. DISCUSSION: This article reviews the common causes of bile duct injury during laparoscopic cholecystectomy and makes recommendations that should help prevent these serious injuries from occurring. CONCLUSIONS: The incidence of bile duct injury during laparoscopic cholecystectomy, although greater than during open cholecystectomy, can be minimized using specific operative strategies and dissection principles.

Endoscopic retrograde cholangiopancreatography and histopathology correlation for chronic pancreatitis.

Endoscopic retrograde cholangiopancreatography (ERCP) is debated as the gold standard for diagnosing and staging chronic pancreatitis (CP). The Cambridge classification grades CP on ECRP findings from normal (Grade I) to marked (Grade V). Comparison is needed with histopathology, which is considered the true gold standard to set the accuracy of any diagnostic test. A retrospective study included patients with CP who underwent ERCP and histopathology examination after surgical resection between 2001 and 2006. ERCP findings were staged according to the Cambridge classification. Thirty-one patients underwent initial diagnostic ERCP and surgical resection for chronic pancreatitis between 2001 and 2006 (61% women, 39% men). Patients with CP were diagnosed based on ERCP findings and the Cambridge classification as having normal (2 of 31 [6.5%]), equivocal (4 of 31 [13%]), mild (3 of 31 [9.7%]), moderate (15 of 31 [48%]), and marked (7 of 31 [23%]) pancreatitis. Patients experienced a mean of 5.5 ERCPs with pancreatic duct stenting before surgery and demonstrated a mean time of 25 months (range, 6 months to 3 years) between initial diagnosis and surgery. Surgeries for chronic pancreatitis included 13 (42%) subtotal pancreatectomies, 10 (32%) Whipples, and 8 (26%) distal pancreatectomies. The ERCP findings and histopathology reports correlated in 23 (74%) patients, whereas in eight (26%), findings did not correlate. The early disease group's (9 of 31 classified as normal, equivocal, or mild) ERCP findings correlated with histopathology in 6 of 9 patients (67%). Patients classified as moderate and marked had a correlation of 17 of 22 (77%). ERCP demonstrates a high correlation with pathology for assessing the severity of CP using the Cambridge classification grading system. Patients with normal, equivocal, or mild disease still represent a difficult patient subset for surgical decision-making. ERCP findings accurately predict pathology and thus should be used to help formulate the surgical plan.

Natural orifice translumenal endoscopic drainage for pancreatic abscesses.

BACKGROUND: Few series describe endoscopic drainage of pancreatic abscesses. Abscesses are complications of pancreatitis, presenting with sepsis, peritonitis, or both. This report describes the feasibility and efficacy of natural orifice translumenal endoscopic surgery for pancreatic abscesses. METHODS: This study reviewed 35 consecutively treated patients for the period 1994-2007. The approaches alone or in combination were transmural (transgastric or transduodenal) and transpapillary. The criteria for abscesses were two or more of the following: fever, abdominal pain, elevated white blood count (WBC), and positive fluid cultures. RESULTS: The 35 patients (19 men and 16 women) had a mean age of 49 years. The abscesses had idiopathic (37%), gallstone (32%), alcohol (20%), and divisum (11%) etiologies. The presenting signs were abdominal pain (80%), positive cultures (69%), fever (57%), elevated WBC (51%), and nausea/vomiting (39%). The approaches for abscess drainage were as follows: transgastric (n = 15, 43%), transduodenal (n = 4, 11%), transgastric combined with transpapillary (n = 8, 23%), transduodenal combined with transpapillary (n = 1, 3%), and transpapillary alone (n = 7, 20%). A total of 28 patients (80%) achieved successful endoscopic pancreatic abscess drainage, whereas 7 (20%) required surgery. Of these seven patients, two (6%) required emergent laparotomy to control bleeding, and the remaining five (14%) were explored after failure to demonstrate clinical improvement from endoscopic drainage. Three patients required internal drainage, and two patients required distal pancreatectomy. The mean follow-up period was 15 months, and the complication rate was 6%. No one died from the procedure. CONCLUSION: Endoscopic surgery for pancreatic abscess is feasible and effective. It is an alternative to surgery that currently can be considered a primary treatment option for selected pancreatic abscesses.