Massimiliano Mutignani

Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomised controlled trial

Background: In chronic pancreatitis, obstruction of the main pancreatic duct (MPD) may contribute to the pathogenesis of pain. Pilot studies suggest that extracorporeal shock wave lithotripsy (ESWL) alone relieves pain in calcified chronic pancreatitis. Aim: To compare ESWL alone with ESWL and endoscopic drainage of the MPD for treatment of pain in chronic pancreatitis. Subjects: Patients with uncomplicated painful chronic pancreatitis and calcifications obstructing the MPD. Methods: 55 patients were randomised to ESWL alone (n = 26) or ESWL combined with endoscopy (n = 29). Results: 2 years after trial intervention, 10 (38%) and 13 (45%) patients of the ESWL alone and ESWL combined with endoscopy group, respectively, had presented pain relapse (primary outcome) (OR 0.77; 95% CI 0.23 to 2.57). In both groups, a similar decrease was seen after treatment in the MPD diameter (mean decrease 1.7 mm; 95% CI 0.9 to 2.6; p<0.001), and in the number of pain episodes/year (mean decrease, 3.7; 95% CI 2.6 to 4.9; p<0.001). Treatment costs per patient were three times higher in the ESWL combined with endoscopy group compared with the ESWL alone group (p = 0.001). The median delay between the onset of chronic pancreatitis and persistent pain relief for both groups was 1.1 year (95% CI 0.7 to 1.6), as compared with 4 years (95% CI 3 to 4) for the natural history of chronic pancreatitis in a reference cohort (p<0.001). Conclusions: ESWL is a safe and effective preferred treatment for selected patients with painful calcified chronic pancreatitis. Combining systematic endoscopy with ESWL adds to the cost of patient care, without improving the outcome of pancreatic pain.

Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study.

OBJECTIVES:Prospective studies have identified a number of patient- and procedure-related independent risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, with different conclusions, so various questions are still open. The endoscopists expertise, case volume, and case mix can all significantly influence the outcome of ERCP procedures, but have been investigated little to date.METHODS:We identified patient- and procedure-related risk factors for post-ERCP pancreatitis and the impact of the endoscopists experience and the centers case volume, using univariate and multivariate analysis, in a multicenter, prospective study involving low- and high-volume centers, over a 6-month period.RESULTS:A total of 3,635 ERCP procedures were included; 2,838 (78%) ERCPs were performed in the 11 high-volume centers (median 257 each) and 797 in the 10 low-volume centers (median 45 each). Overall, 3,331 ERCPs were carried out by expert operators and 304 by less-skilled operators. There were significantly more grade 3 difficulty procedures in high-volume centers than in low-volume ones (P<0.0001). Post-ERCP pancreatitis occurred in 137 patients (3.8%); the rates did not differ between high- and low-volume centers (3.9% vs. 3.1%) and expert and non-expert operators (3.8% vs. 5.5%). However, in high-volume centers, there were 25% more patients with patient- and procedure-related risk factors, and the pancreatitis rate was one-third higher among non-expert operators. Univariate analysis found a significant association with pancreatitis for history of acute pancreatitis, either non-ERCP- or ERCP-related and recurrent, young age, absence of bile duct stones, and biliary pain among patient-related risk factors, and >10 attempts to cannulate the Vaters papilla, pancreatic duct cannulation, contrast injection of the pancreatic ductal system, pre-cut technique, and pancreatic sphincterotomy, among procedure-related risk factors. Multivariate analysis also showed that a history of post-ERCP pancreatitis, biliary pain, >10 attempts to cannulate the Vaters papilla, main pancreatic duct cannulation, and pre-cut technique were significantly associated with the complication.CONCLUSIONS:A history of pancreatitis among patient-related factors, and multiple attempts at cannulation among procedure-related factors, were associated with the highest rates of post-ERCP pancreatitis. Pre-cut sphincterotomy, although identified as another significant risk factor, appeared safer when done early (fewer than 10 attempts at cannulating), compared with repeated multiple cannulation. The risk of post-ERCP pancreatitis was not associated with the case volume of either the single endoscopist or the center; however, high-volume centers treated a larger proportion of patients at high risk of pancreatitis and did a significantly greater number of difficult procedures.

Extracorporeal shock wave lithotripsy of pancreatic stones in chronic pancreatitis: immediate and medium-term results

BACKGROUND Obstruction of the main pancreatic duct with upstream hypertension and dilation is a cause of pain in patients with chronic pancreatitis. Pancreatic ductal drainage can be achieved endoscopically by intraductal stone removal after endoscopic pancreatic sphincterotomy and/or by insertion of a pancreatic stent. Extracorporeal shock wave lithotripsy may be needed whenever stones cannot be removed by endoscopic procedures. We present our results in 35 patients treated with a combined endoscopic-extracorporeal shock wave lithotripsy approach with at least 6 months of follow-up. METHODS Thirty-five patients with severe chronic pancreatitis were treated by extracorporeal shock wave lithotripsy for endoscopically unretrievable obstructive stones. Extracorporeal shock wave lithotripsy was performed with an electromagnetic lithotriptor in 29 patients and an electrohydraulic lithotriptor in 6. RESULTS The procedures were well tolerated by the majority of patients. Fragmentation of stones was obtained in all cases while complete clearance and decompression of pancreatic duct were obtained in 26 of 35 (74.3%) and in 30 of 35 (85.7%) cases, respectively. There was no mortality related to the procedure. Morbidity was observed in 8 of 35 patients (22.8%). CONCLUSIONS Extracorporeal shock wave lithotripsy is a safe and effective treatment for endoscopically unretrievable pancreatic stones in the main pancreatic duct. Extracorporeal shock wave lithotripsy should be considered complementary and not an alternative to endoscopic drainage. Combined with endoscopy, extracorporeal shock wave lithotripsy may increase the success rate of nonsurgical treatment of patients with chronic pancreatitis.

Chronic pancreatitis: report from a multicenter Italian survey (PanCroInfAISP) on 893 patients.

BACKGROUND No data on chronic pancreatitis in Italy are available yet. AIM To evaluate demographic, clinical, diagnostic and therapeutic aspects in patients suffering from chronic pancreatitis. PATIENTS AND METHODS Eligible patients were prospectively enrolled from 2000 to 2005. Information concerning demographic data, lifestyle risk factors, family and clinical history, associated factors (alcohol, autoimmunity, cystic dystrophy of the duodenal wall, obstruction, genetic mutations) concomitant diseases, diagnostic findings, and pharmacological, endoscopic and surgical therapy were gathered. RESULTS 893 patients (74% males, mean age 53.7+/-15.2 years) were evaluated. 519/859 patients (60%) were drinkers and 555/840 (66%) were smokers. A strong positive correlation between drinking and cigarette consumption (R=0.53; p<0.0001) was found. Heavy alcohol consumption (>80g of alcohol/day for more than 5 years) was considered the most important risk factor in 300 patients (34%), obstruction in 238 (27%), alcohol and obstruction in 82 (9%), autoimmunity in 34 (4%), cystic dystrophy of the duodenal wall/groove pancreatitis in 55 (6%), gene mutations in 36 (4%), and none (idiopathic) in 148 (17%). Bile stones were diagnosed in 287 patients (33%) and cholecystectomy was performed in 329 patients (38%). Pancreatic calcifications were diagnosed in 547/879 patients (62%). Pancreatic surgery was performed in 273 patients (31%). Endoscopic sphincterotomy was performed in 371 patients (42%). Exocrine and endocrine insufficiency were found, respectively, in 373/834 (45%) and 275/885 patients (31%). CONCLUSIONS An unexpected low frequency of alcohol abuse and new emerging associated risk factors for chronic pancreatitis were observed in Italy.

Prospective evaluation of a new self-expanding plastic stent for inoperable esophageal strictures

BACKGROUND High stent cost is considered the major drawback of self-expanding metal stents for dysphagia palliation in patients with inoperable esophageal strictures. We report our experience with a self-expanding plastic (Polyflex) stent, the cost of which is half that of the metal stents. METHODS Between September 1999 and April 2001, 16 dysphagic patients (15 men; mean age, 69.4 +/- 14.5 years; range, 49-100 years; mean dysphagia score, 3.31 +/- 0.6) with esophageal strictures who underwent Polyflex stent placement (insertion device diameter, 12-14 mm; postexpansion inner stent diameter, 16-21 mm; stent length, 9, 12, and 15 cm) were studied prospectively. The strictures were caused by postsurgical recurrence of gastric/esophageal cancer at the anastomotic site in five patients, primary esophageal cancer in four patients, esophagocardia junction cancer in four patients, metastatic mediastinal lymph nodes from a primary lung cancer invading the esophagus in 1 patient, and benign peptic stricture in two elderly patients. All the patients were prospectively followed until death. RESULTS Stent insertion was technically successful in 12 patients (75%). Stent placement failed in four patients (25%) because of failure to pass the delivery catheter across the stricture in three patients and failure of the stent to open in one patient. Early and late stent migration occurred in two patients and 1 patient, respectively. Tumor overgrowth occurred in 1 patient. The mean dysphagia score 7 days after stent placement was 1.1 +/- 0.9. Mean survival was 100.6 +/- 71.2 days (range, 8-225 days). CONCLUSION Self-expanding Polyflex stents are safe and effective for inoperable esophageal strictures and have an acceptable technical success rate. Further experience, better selection criteria, and design improvements should improve results.

Italian consensus guidelines for chronic pancreatitis

This paper gives practical guidelines for diagnosis and treatment of chronic pancreatitis. Statements have been elaborated by working teams of experts, by searching for and analysing the literature, and submitted to a consensus process by using a Delphi modified procedure. The statements report recommendations on clinical and nutritional approach, assessment of pancreatic function, treatment of exocrine pancreatic failure and of secondary diabetes, treatment of pain and prevention of painful relapses. Moreover, the role of endoscopy in approaching pancreatic pain, pancreatic stones, duct narrowing and dilation, and complications was considered. Recommendations for most appropriate use of various imaging techniques and of ultrasound endoscopy are reported. Finally, a group of recommendations are addressed to the surgical treatment, with definition of right indications, timing, most appropriate procedures and techniques in different clinical conditions and targets, and clinical and functional outcomes following surgery.

Endotherapy of postoperative biliary strictures with multiple stents: results after more than 10 years of follow-up

BACKGROUND Endoscopic dilation of postoperative biliary strictures with increasing numbers of stents was first described by our group in 2001 with promising results after a long-term follow-up (mean 4 years). OBJECTIVE To verify results of endoscopic treatment of postoperative biliary strictures at a very-long-term follow-up. DESIGN Single center, follow-up study. SETTING Tertiary-care, academic referral center. PATIENTS A group of 42 patients from our 2001 study, who had undergone endoscopic dilation of postoperative biliary strictures with the multiple endoscopic stenting technique, underwent systematic follow-up. The last telephone follow-up was done in September 2009. INTERVENTION Clinical conditions and the occurrence of new biliary symptoms during the follow-up period were assessed, and results of the most recent liver function tests and abdominal US were recovered. MAIN OUTCOME MEASUREMENTS Occurrence of cholangitis and liver function test evaluation during the follow-up period. RESULTS Of the 40 patients who were alive at the end of the study published in 2001, 5 (12.5%) died of unrelated causes after a mean of 6.7 years (range 3-13.3 years) from the end of treatment, without further biliary symptoms. The overall mean follow-up time for the remaining 35 patients (87.5%) was 13.7 years (range 11.7-19.8 years). Seven patients (20%) experienced recurrent acute cholangitis after a mean of 6.8 years (range 3.1-11.7 years) from the end of treatment. All 7 of these patients underwent ERCP. Four of the 7 patients had postoperative biliary stricture recurrence (n = 4/35, 11.4%) that was retreated endoscopically with placement of stents, and the other 3 patients had common bile duct stones (n = 3/35, 8.6%) that were extracted. No stricture or bile duct stone recurrences after retreatment were recorded after a mean follow-up period of a further 7.1 years (range 2.5-12.1 years). Twenty-eight patients remained asymptomatic with normal liver function test results and abdominal US results after a mean follow-up period of 13.7 years (range 11.7-19.8 years). LIMITATIONS Telephone follow-up. CONCLUSION Results of multiple endoscopic stenting for postoperative biliary strictures remain excellent even after a very-long-term follow-up. The stricture recurrence rate is low, and recurrences can be retreated endoscopically.

COMBINED MODALITY TREATMENT IN UNRESECTABLE EXTRAHEPATIC BILIARY CARCINOMA

PURPOSE Cancers of the extrahepatic biliary tract are rare. Surgical resection is considered the standard treatment, but is rarely feasible. Several reports of combined modality therapy, including external beam radiation, often combined with chemotherapy and intraluminal brachytherapy, have been published. The purpose of this study was to evaluate the effect of chemoradiation plus intraluminal brachytherapy on response, local control, survival, and symptom relief in patients with unresectable or residual extrahepatic biliary carcinoma. METHODS AND MATERIALS From February 1991 to December 1997, 20 patients (14 male, 6 female; mean age 61 +/- 12 years; median follow-up 71 months) with unresectable (16 patients) or residual (4 patients), nonmetastatic extrahepatic bile tumors (common bile duct, 8; gallbladder, 1; Klatskin, 11) received external beam radiation (39.6-50.4 Gy); in 19 patients, 5-fluorouracil (96-h continuous infusion, days 1-4 at 1,000 mg/m(2)/day) was also administered. Twelve patients received a boost by intraluminal brachytherapy using (192)Ir wires of 30-50 Gy, prescribed 1 cm from the source axis. RESULTS During external beam radiotherapy, 8 patients (40%) developed grade 1-2 gastrointestinal toxicity. Four patients treated with external-beam plus intraluminal brachytherapy had a clinical response (2 partial, 2 complete) after treatment. For the total patient group, the median survival and time to local progression was 21.2 and 33.1 months, respectively. Distant metastasis occurred in 10 (50%) patients. Two patients who received external beam radiation plus intraluminal brachytherapy developed late duodenal ulceration. Two patients with unresectable disease survived more than 5 years. CONCLUSION Our data suggest that chemoradiation plus intraluminal brachytherapy was relatively well-tolerated, and resulted in reasonable local control and median survival. Further follow-up and additional research is needed to determine the ultimate efficacy of this regimen. New chemoradiation combinations and/or new treatment strategies (neoadjuvant chemoradiation) may contribute, in the future, to improve these results.

Efficacy of main pancreatic-duct endoscopic drainage in patients with chronic pancreatitis, continuous pain, and dilated duct

BACKGROUND The aim of endoscopic treatment in patients with chronic pancreatitis is to achieve decompression of the pancreatic duct, because duct obstruction with increased pressure within the duct is one of the leading causes of pain in these patients. The majority of patients suffer from relapsing pain, thus making it difficult to evaluate the efficacy of therapy. The outcome of endoscopic treatment on pain has been evaluated in patients with continuous pain (present for more than 1 month, at least 5 days per week, requiring daily analgesic therapy) and dilated duct. METHODS Of 343 patients who underwent endotherapy for chronic pancreatitis in a 15-year period, 22 (6.4%)(19 men, mean age 48 years, alcohol abuse 14) had continuous pain and a dilated pancreatic duct. RESULTS Endotherapy was successful in all patients, with no procedure-related mortality and only mild complications. Pain disappeared, and analgesics could be discontinued in all patients immediately after endotherapy. Six patients are pain free after a mean period of 5.5 years. One pain-free patient died after 3.4 years from myocardial infarction. Five patients were successfully endoscopically re-treated for pain relapses. Four patients underwent surgery for frequent pain relapses after a mean period of 2.5 years. Six patients were lost to follow-up. CONCLUSIONS Endotherapy should be considered as the initial treatment of choice in patients with chronic pancreatitis, dilated duct, and continuous pain.

Hydrophilic hydromer-coated polyurethane stents versus uncoated stents in malignant biliary obstruction: a randomized trial

BACKGROUND Hydromer-coated polyurethane stents (HCPS) have a low coefficient of friction that may reduce sludge formation and potentially increase stent longevity. METHODS Eighty-three patients (39 men, mean age 69.3 years) with malignant mid or distal bile duct strictures were prospectively randomized to receive either 10F HCPS (n = 40) or standard polyethylene stents (n = 43). RESULTS Fifteen patients (18.1%) underwent surgery after stent insertion. Six patients were lost to follow-up (7.2%), whereas 34 died of the underlying disease without evidence of stent occlusion (15 HCPS group and 19 polyethylene group). Median survival was 75 days (range 15 to 372 days) and 108 days (range 25 to 325 days) in the HCPS and polyethylene stent groups, respectively (p = not significant). Stent occlusion was observed in 25 patients (42%), 16 with HCPS stents and 9 with polyethylene stents, with a median patency of 103 days (range 40 to 280 days) and 68 days (range 32 to 175 days), respectively (p = not significant). CONCLUSIONS HCPS do not appear to provide significant clinical advantages in terms of stent longevity over standard plastic prostheses.