Milton T. Smith

Stent-induced pancreatic ductal and parenchymal changes: correlation of endoscopic ultrasound with ERCP

BACKGROUND Polyethylene pancreatic duct stents induce morphologic changes of the pancreatic duct in the majority of patients. This study was undertaken to determine if parenchymal abnormalities are present in patients undergoing short-term pancreatic duct stenting and to correlate these findings with the pancreatogram obtained at stent removal. METHODS Twenty-five patients underwent pancreatic duct stenting and had an endoscopic ultrasound evaluation of the pancreas at stent removal. The pancreatograms were evaluated at stent removal for ductal irregularity, narrowing, and side branch changes. Endoscopic ultrasound was used to assess for differences in the echo characteristics of the pancreatic parenchyma around the stent compared with the rest of the gland. RESULTS Of the 16 patients evaluated by ERCP at stent removal, 9 (56%) had 1 or more new ductographic changes. Endoscopic ultrasound identified parenchymal changes in the stented region in 17 of 25 patients (68%). Four patients who had parenchymal changes in the stented region on endoscopic ultrasound at stent removal had a follow-up study at a mean time of 16 months. Two patients had (new) changes suggestive of focal chronic pancreatitis in the stented region. CONCLUSION Short-term pancreatic duct stenting induced both ductal and parenchymal changes in more than 50% of patients. Chronic pancreatitis may be a consequence of pancreatic duct stenting.

Post-ERCP pancreatitis: randomized, prospective study comparing a low- and high-osmolality contrast agent.

Diagnostic and therapeutic ERCPs are complicated by pancreatitis in 1% to 10% of patients, and evidence suggests that the contrast agent used for ERCP may be important in the pathogenesis of such pancreatitis. This prospective, double-blind study was undertaken to determine whether the use of a low-osmolality, nonionic contrast agent (Omnipaque 300; iohexol, 672 mOsm/kg H2O) would reduce the frequency and severity of postprocedure pancreatitis as compared to a high-osmolality, ionic contrast agent (Hypaque 50%; diatrizoate sodium, 1515 mOsm/kg H20). Six hundred ninety patients undergoing diagnostic ERCP (pancreatogram, cholangiogram, or both) either with or without sphincter of Oddi manometry and therapy were randomized to iohexol or diatrizoate sodium. Postprocedure pancreatitis was diagnosed when the serum amylase or lipase level was elevated to at least four times the upper limits of normal at 18 hours and was associated with increased abdominal pain persisting for at least 24 hours after the procedure that required administration of narcotic analgesics. The pancreatitis was graded as mild, moderate, or severe depending on the length of hospital stay and the need for intervention. The overall frequency (7.2% versus 7.5%) and severity (4.3% mild, 2% moderate, 0.9% severe for the diatrizoate sodium group versus 4.3% mild, 2.6% moderate, and 0.6% severe for the iohexol group) of postprocedure pancreatitis and the frequency and severity within each procedure category were similar for the two contrast agent groups (p > .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of meperidine on the pancreatic and biliary sphincter

BACKGROUND Opioids are traditionally avoided during sphincter of Oddi manometry because of indirect evidence suggesting that these agents cause sphincter of Oddi spasm. This study was undertaken to determine the direct effects of meperidine on the biliary and pancreatic sphincter. METHODS Forty-seven patients were prospectively evaluated by sphincter of Oddi manometry in the conventional retrograde fashion. Manometry was initially performed with intravenous diazepam sedation alone. The manometry was repeated 3 to 5 minutes after meperidine was administered. RESULTS The basal sphincter pressure of the biliary sphincter, pancreatic sphincter, and the combined sphincter group were not significantly altered by meperidine. Concordance (normal versus abnormal) between the basal sphincter pressure before and after meperidine was seen in 44 of 47 patients (94%). Meperidine produced a significant increase in the pancreatic, biliary, and combined sphincter phasic frequency and a significant decrease in the phasic duration. The pancreatic and combined sphincter phasic pressures were significantly reduced following meperidine administration. Seventeen manometry tracings (36%) were believed to be qualitatively better after meperidine, while only four (8.5%; p < .001) were qualitatively better with diazepam alone. CONCLUSION Meperidine can be used for additional analgesia during sphincter of Oddi manometry if the basal sphincter pressure is the parameter used to determine therapy.

Long-term outcomes after total pancreatectomy and islet cell autotransplantation: is it a durable operation?

Objective:Total pancreatectomy and islet cell autotransplantation (TPIAT) has been increasingly utilized for the management of chronic pancreatitis (CP) with early success. However, the long-term durability of this operation remains unclear. Methods:All patients undergoing TPIAT for the treatment of CP with 5-year or greater follow-up were identified for inclusion in this single-center observational study. End points included narcotic requirements, glycemic control, islet function, quality of life (QOL), and survival. Results:Between 2000 and 2013, 166 patients underwent TPIAT; 112 of these patients had 5-year follow-up data to analyze. All patients underwent successful IAT with a mean of 6027 ± 595 islet equivalents per body weight. There was no perioperative mortality and actuarial survival at 5 years was 94.6%. The narcotic independence rate at 1 year was 55% and continued to improve to 73% at 5-year follow-up (P < 0.05). The insulin independence rate declined over time (38% at 1 year vs 27% at more than 5 years), but insulin requirements remained similar (21.4 vs 24.3 units per day, P = 0.6). All patients achieved stable glycemic control with a median hemoglobin A1C (HgA1C) of 6.9% (range: 5.85%–8.3%). The short form 36-item QOL assessment of a subset of patients available for contact demonstrated continued improvements in all tested modules in patients with at least 5-year follow-up. Two patients developed diabetic complications requiring whole organ pancreas transplant for salvage. Conclusions:This represents one of the largest series examining long-term outcomes after TPIAT. This operation produces durable pain relief and improvement in QOL parameters. Insulin independence rates decline over time, but most patients maintain stable glycemic control.

Total pancreatectomy and islet cell autotransplantation as a means of treating patients with genetically linked pancreatitis

BACKGROUND For patients with severe chronic pancreatitis, total or completion pancreatectomy with islet cell autotransplantation (IAT) can alleviate pain and avoid the complications of diabetes. Several genetic mutations, specifically, PRSS1, CFTR, and SPINK1, are associated with chronic pancreatitis. Few reports have focused on the benefit of this operation for this subset of patients. METHODS Between February 2000 and July 2009, 118 patients were treated with total pancreatectomy and IAT for chronic pancreatitis. Patients with known genetic mutations were then selected for further analysis. RESULTS Of the 188 patients, 16 (13.6%) patients were identified as having genetic mutations, including CFTR (n = 10), PRSS1 (n = 4), and SPINK1 (n = 2) mutations. Mean patient age was 31.4 years (range, 15-59) with an equal male-to-female ratio (50:50). Preoperatively, patients required an average of 185 ± 60 morphine equivalents (MEQ) (median, 123 MEQ) for preoperative pain control. No patients were taking insulin before operation. After resection with IAT, patients were discharged from the hospital with a daily average of 22 ± 4 units of insulin with 6 (38%) patients requiring fewer than 15 units of insulin at the time of discharge. At a mean follow-up of 22 months, mean insulin requirements decreased to 15 U/d (P = .0172). A total of 7 (44%) patients required 15 or fewer units daily, and 4 (25%) patients were completely insulin-independent. Average daily narcotic usage at most recent follow-up decreased to 70 MEQ (median, 0) with 10 (63%) patients currently narcotic-independent. Analyses of the 36-item short-form health survey and the McGill Pain Questionnaire demonstrated a significant improvement in quality-of-life parameters and pain assessment. CONCLUSION In patients who suffer from genetically linked chronic pancreatitis, pancreatic resection with IAT should be considered as an early therapeutic option to decrease chronic abdominal pain while preserving endogenous endocrine function.

Factors associated with recidivism following pancreaticoduodenectomy

OBJECTIVES Factors related to readmission after pancreaticoduodenectomy (PD) may include postoperative morbidity and the functional status of the patient. This study aimed to retrospectively review our institutions experience of readmission of patients who had undergone Whipple procedure PD. METHODS Recidivism was defined as readmission to the primary or a secondary hospital within, respectively, 30 days, 30-90 days or 90 days postoperatively. Associations between recidivism, perioperative factors and patient characteristics were evaluated. RESULTS During the past 5 years, 30-day, 30-90-day and 90-day recidivism rates were 14.5%, 18.5% and 27.4%, respectively. The most common reasons for readmission included dehydration and/or malnutrition (37.5% of readmissions) and pain (12.5%). Patients who underwent PD for chronic pancreatitis were more likely to be readmitted within 90 days of surgery than patients who underwent PD for malignancy (P < 0.01). Intraoperative transfusion was also associated with 30-90-day and 90-day recidivism (P < 0.01). Preoperative comorbidities, including Charlson Comorbidity Index score, number of pre-discharge complications, type of Whipple reconstruction, preoperative biliary stenting, need for vascular reconstruction and patient body mass index were not associated with recidivism. CONCLUSIONS Our data confirm previous reports indicating high rates of readmission after PD. To our knowledge, this report is the first to demonstrate chronic pancreatitis as an independent risk factor for readmission.

Total pancreatectomy with islet cell autotransplantation as the initial treatment for minimal-change chronic pancreatitis.

OBJECTIVES Patients with minimal-change chronic pancreatitis (MCCP) are traditionally managed medically with poor results. This study was conducted to review outcomes following total pancreatectomy with islet cell autotransplantation (TP/IAT) as the initial surgical procedure in the treatment of MCCP. METHODS All patients submitted to TP/IAT for MCCP were identified for inclusion in a single-centre observational study. A retrospective chart review was performed to identify pertinent preoperative, perioperative and postoperative data. RESULTS A total of 84 patients with a mean age of 36.5 years (range: 15-60 years) underwent TP/IAT as the initial treatment for MCCP. The most common aetiology of chronic pancreatitis in this cohort was idiopathic (69.0%, n = 58), followed by aetiologies associated with genetic mutations (16.7%, n = 14), pancreatic divisum (9.5%, n = 8), and alcohol (4.8%, n = 4). The most common genetic mutations pertained to CFTR (n = 9), SPINK1 (n = 3) and PRSS1 (n = 2). Mean ± standard error of the mean preoperative narcotic requirements were 129.3 ± 18.7 morphine-equivalent milligrams (MEQ)/day. Overall, 58.3% (n = 49) of patients achieved narcotic independence and the remaining patients required 59.4 ± 10.6 MEQ/day (P < 0.05). Postoperative insulin independence was achieved by 36.9% (n = 31) of patients. The Short-Form 36-Item Health Survey administered postoperatively demonstrated improvement in all tested quality of life subscales. CONCLUSIONS The present report represents one of the largest series demonstrating the benefits of TP/IAT in the subset of patients with MCCP.

Completion pancreatectomy and islet cell autotransplantation as salvage therapy for patients failing previous operative interventions for chronic pancreatitis.

PURPOSE Traditional decompressive and/or pancreatic resection procedures have been the cornerstone of operative therapy for refractory abdominal pain secondary to chronic pancreatitis. Management of patients that fail these traditional interventions represents a clinical dilemma. Salvage therapy with completion pancreatectomy and islet cell autotransplantation (CPIAT) is an emerging treatment option for this patient population; however, outcomes after this procedure have not been well-studied. METHODS All patients undergoing CPIAT after previous decompressive and/or pancreatic resection for the treatment of chronic pancreatitis at our institution were identified for inclusion in this single-center observational study. Study end points included islet yield, narcotic requirements, glycemic control, and quality of life (QOL). QOL was assessed using the Short Form (SF)-36 health questionnaire. RESULTS Sixty-four patients underwent CPIAT as salvage therapy. The median age at time of CPIAT was 38 years (interquartile range [IQR], 14.7-65.4). The most common etiology of chronic pancreatitis was idiopathic pancreatitis (66%; n = 42) followed by genetically linked pancreatitis (9%; n = 6) and alcoholic pancreatitis (8%; n = 5). All of these patients had previously undergone prior limited pancreatic resection or decompressive procedure. The majority of patients (50%; n = 32) underwent prior pancreaticoduodenectomy, whereas the remainder had undergone distal pancreatectomy (17%; n = 11), Frey (13%; n = 8), Puestow (13%; n = 8), or Berne (8%; n = 5) procedures. Median time from initial surgical intervention to CPIAT was 28.1 months (IQR, 13.6-43.0). All of these patients underwent a successful CPIAT. Mean operative time was 502.2 minutes with average hospital duration of stay of 13 days. Islet cell isolation was feasible despite previous procedures with a mean islet yield of 331,304 islet cell equivalents, which totaled an islet cell autotransplantation of 4,737 ± 492 IEQ/kg body weight. Median patient follow-up was 21.2 months (IQR, 7.9-36.8). Before CPIAT, all patients required a mean of 120.8 morphine equivalent milligrams per day (MEQ/d), which improved to 48.5 MEQ (P < .001 compared with preoperative requirements) at most recent follow-up. Of these patients, 44% (n = 28) achieved narcotic independence. All patients were able to achieve stable glycemic control with a mean insulin requirement of 16 units per day. Of these patients, 20% (n = 13) were insulin independent after CPIAT. Mean postoperative glycosylated hemoglobin was 7.8% (range, 4.6-12.5). Islet cell viability was confirmed with endocrine testing and mean C-peptide levels 6 months after CPIAT were 0.91 ng/mL (range, 0.1-3.0). The SF-36 QOL survey administered postoperatively demonstrated improvement in all tested modules. CONCLUSION This study is the first to examine the results of salvage therapy with CPIAT for patients with refractory chronic pancreatitis. Patients undergoing CPIAT achieved improved postoperative narcotic requirements, stable glycemic control, and improved QOL.

Does radiologic response correlate to pathologic response in patients undergoing neoadjuvant therapy for borderline resectable pancreatic malignancy

In patients with borderline resectable pancreas cancers, clinicians frequently consider radiographic response as the primary driver of whether patients should be offered surgical intervention following neoadjuvant therapy (NT). We sought to determine any correlation between radiographic and pathologic response rates following NT.

Endoscopic and Percutaneous Biliary Drainage Procedures: Role in Preoperative Management, Diagnosis, and Palliation

Most patients with pancreatic cancer develop obstructive jaundice. Management of malignant biliary obstruction is dependent upon factors such as certainty of the diagnosis, symptoms, and resectability status of the patient. Tissue sampling during endoscopic retrograde cholangiopancreatography (ERCP) has a relatively low sensitivity but high specificity. Surgical resection is the only potentially curative treatment option. Patients with obstructive jaundice have various pathophysiological changes that affect the liver, kidney, heart, and the immune system, potentially increasing the risk of postoperative complications following pancreaticoduodenectomy. However, the role of routine preoperative biliary drainage (PBD) in the management of jaundiced patients with resectable pancreatic cancer is controversial. Most clinical studies have failed to show a clear advantage for patients undergoing PBD and have advised against routinely performing these procedures. PBD appears to increase overall morbidity because of procedure-related complications, especially if plastic stents are used for biliary decompression. Self-expandable metal stents (SEMS) have a longer patency and could reduce the risk of stent-related complications due to early occlusion. PBD may be beneficial in selected patients including those with cholangitis, when surgery is delayed, or when neoadjuvant therapy is planned. ERCP with placement of a short SEMS is the preferred modality and does not interfere with subsequent pancreaticoduodenectomy. Percutaneous and EUS-guided biliary drainage procedures are useful alternatives when ERCP is unsuccessful. SEMS placement is useful as palliation for patients with unresectable disease.