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.

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.

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.

The microbiology of secondary and postoperative pancreatic infections: implications for antimicrobial management.

HYPOTHESIS: We reviewed our experience with secondary pancreatic infections with a focus on preemptive intervention and the potential alteration of the recovered microbial flora. The pathogens associated with postoperative pancreatic infections were analyzed with respect to nonenteric organisms, if any, that were recovered. We hypothesized that our findings might alter the antimicrobial management of these patients. DESIGN: Retrospective review. SETTING: Hospitals affiliated with the University of Tennessee Health Science Center, Memphis. PATIENTS: Patients developing secondary and postoperative pancreatic infections following severe acute pancreatitis. METHODS: Factors examined relative to secondary pancreatitis included preoperative antibiotic use and antecedent extrapancreatic infections potentially implicated in seeding the pancreatic bed. Patients who had elective resection received 24 to 48 hours of antibiotic prophylaxis. RESULTS: Twenty-two patients required surgery for secondary infections following severe acute pancreatitis, with 29 pathogenic isolates being recovered. Of these 22 patients, 14 received vancomycin hydrochloride prior to surgical intervention. Of those 14 patients, 6 had isolates recovered at the time of surgery that were positive for Enterococcus faecalis and 5 of these isolates were vancomycin resistant. Eight of the 22 patients received antifungal prophylaxis with no fungi recovered from intraoperative culture. However, 2 of the 14 patients who did not receive empiric therapy had isolates that were positive for fungi. Five patients who required an urgent operation for sepsis had pathogenic isolates that were similar to those recovered from central lines. Postoperative infections occurred in 40 of 225 patients (17.8%) who had an elective pancreatic resection, with 72 pathogenic isolates being recovered. Of these 40 patients, 22 (55.0%) had polymicrobial infections. Of the 72 pathogenic isolates recovered from patients, 34 (47.2%) were gram-positive organisms, 15 (20.8%) were fungal organisms, and 17 (23.6%) were drug-resistant bacteria. CONCLUSIONS: Prolonged vancomycin use in patients with severe acute pancreatitis is associated with the acquisition of vancomycin-resistant enterococci. Empiric antifungal therapy may reduce the incidence of secondary fungal pancreatic infections. Systemic bloodstream infections at extrapancreatic sites can lead to seeding of pancreatic pseudocysts. Postoperative infections frequently include gram-positive, fungal, and drug-resistant organisms, and empiric therapy directed at these pathogens should be utilized until definitive culture results are obtained.

Salvage of inaccessible arteriovenous fistulas in obese patients: a review of 132 brachiocephalic fistulas.

The two main factors leading to a functional fistula are maturity and accessibility. The aim of this review was to describe a technique of superficialization for inaccessible brachiocephalic fistulas, and to identify the patients that benefit from superficialization. One hundred and thirty-two brachiocephalic arteriovenous fistulas developed from November 2003 to December 2006 were reviewed for primary maturation. In the mature group, patients were evaluated for fistula accessibility. Inaccessible fistulas were selected for superficialization via our technique of vein mobilization using small skip incisions. Analysis of superficialized and nonsuperficialized groups included age, demographics, and comorbidities. Ninety-nine patients were in the mature group, and 33 in the immature group; primary nonmaturation was 25 per cent. Analysis within the mature group was between nonsuperficialized (n = 81) and superficialized (n = 18) patients. The superficialized group had less hypertension (83% vs 98%, P < 0.05), significantly higher BMI (31 vs 27, P < 0.05), and was mostly female (78% vs 49%, P < 0.05). All superficialized fistulas accommodated successful hemodialysis postoperatively. To conclude, patients with mature but inaccessible fistulas were salvaged by superficialization. This population had significantly higher BMI, less hypertension, and female prevalence. Identifying these patients is important because salvage of their fistula can prevent premature progression to alternate autogenous arteriovenous access procedures.

Globular amyloid beta-peptide oligomer - a homogenous and stable neuropathological protein in Alzheimer's disease.

Amyloid beta-peptide (Abeta)(1-42) oligomers have recently been discussed as intermediate toxic species in Alzheimer's disease (AD) pathology. Here we describe a new and highly stable Abeta(1-42) oligomer species which can easily be prepared in vitro and is present in the brains of patients with AD and Abeta(1-42)-overproducing transgenic mice. Physicochemical characterization reveals a pure, highly water-soluble globular 60-kDa oligomer which we named 'Abeta(1-42) globulomer'. Our data indicate that Abeta(1-42) globulomer is a persistent structural entity formed independently of the fibrillar aggregation pathway. It is a potent antigen in mice and rabbits eliciting generation of Abeta(1-42) globulomer-specific antibodies that do not cross-react with amyloid precursor protein, Abeta(1-40) and Abeta(1-42) monomers and Abeta fibrils. Abeta(1-42) globulomer binds specifically to dendritic processes of neurons but not glia in hippocampal cell cultures and completely blocks long-term potentiation in rat hippocampal slices. Our data suggest that Abeta(1-42) globulomer represents a basic pathogenic structural principle also present to a minor extent in previously described oligomer preparations and that its formation is an early pathological event in AD. Selective neutralization of the Abeta globulomer structure epitope is expected to have a high potential for treatment of AD.

The vacuum chest wall lifter: an innovative, nonsurgical addition to the management of pectus excavatum.

PURPOSE: This report describes the authors' experience using a vacuum to pull the abnormal chest wall outward in patients with pectus excavatum. METHODS: A suction cup was used to create a vacuum at the chest wall. A patient-activated hand pump was used to reduce pressure up to 15% below atmospheric pressure. The device was used by 60 patients (56 males, 4 females), aged 6.1 to 34.9 years (median, 14.8 years), for a minimum of 30 minutes, twice a day, up to 5 hours per day (median, 90 minutes). Patient progress was documented using photography, radiography, and plaster casts of the defect. In 14 children this method was used during the Nuss procedure to enlarge the retrosternal space for safer passage of the introducer. RESULTS: Follow-up occurred between 2 and 18 months (median, 10 months). Computed tomographic scans showed that the device lifted the sternum and ribs within 1 to 2 minutes; this was confirmed thoracoscopically during the Nuss procedure. The suction cup enlarged the retrosternal space for safer passage of the introducer. Initially, the sternum sank back after few minutes. After 1 month, an elevation of 1 cm was noted in 85% of the patients. After 5 months, the sternum was lifted to a normal level in 12 patients (20%) when evaluated immediately after using the suction cup. All patients exhibited moderate subcutaneous hematoma, although the skin was not injured. One patient suffered from transient paresthesis in the right arm and leg. Two patients experienced orthostatic disturbances during the first application of the suction cup. There were no other complications. DISCUSSION: In patients with pectus excavatum, application of a vacuum effectively pulled the depressed anterior chest wall forward. The initial results proved dramatic, although it is not yet known how much time is required for long-term correction. CONCLUSIONS: This vacuum method holds promise as a valuable adjunct treatment in both surgical and nonsurgical correction of pectus excavatum.

Effects of 8-chlorodeoxyadenosine on DNA synthesis by the Klenow fragment of DNA polymerase I.

8-chloro-2'-deoxyadenosine (8-Cl-dAdo) was incorporated into synthetic DNA oligonucleotides to determine its effects on DNA synthesis by the 3'-5' exonuclease-free Klenow fragment of Escherichia coli DNA Polymerase I (KF-). Single nucleotide insertion experiments were used to determine the coding potential of 8-Cl-dAdo in a DNA template. KF- inserted TTP opposite 8-Cl-dAdo in the template, but with decreased efficiency relative to natural deoxyadenosine. Running-start primer extensions with KF- resulted in polymerase pausing at 8-Cl-dAdo template sites during DNA synthesis. The 2'-deoxyribonucleoside triphosphate analogue, 8-Cl-dATP, was incorporated opposite thymidine (T) approximately two-fold less efficiently than dATP.