Pancolitis with ischemic injury as a complication of immunosuppressive treatment in a patient with autoimmune hepatitis: a case report.

Ischemic colitis is a serious drug-induced adverse event. There are only few cases of immunosuppression-associated ischemic colitis described in the literature, but none with a pancolitis-like manifestation. We report the case of a 72-year-old female patient who developed a pancolitis with ischemic injury on immunosuppressive treatment with steroids and azathioprine for autoimmune hepatitis. The patient presented with massive rectal bleeding. Colonoscopy confirmed the diagnosis of pancolitis. The results of histological examination indicated drug-induced ischemic colitis involving the entire colon. This is the first case of ischemic pancolitis mimicking an inflammatory bowel disease (IBD) in a patient with immunosuppressive therapy.

Packing properties of starch-based powders under mild mechanical stress.

This study reports the ability to settle of commercial pharmaceutical grade starch samples, both native and pregelatinized. The experiments were carried out under different relative humidity (RH%) conditions and the packing properties were evaluated using both official pharmacopoeial monograph conditions and also modified conditions in order to give a deeper knowledge of tapping under mild mechanical stress. The technique adopted, simulating common pharmaceutical operating practices, appears to be useful to estimate some technologically relevant features of diluent powder materials. Moreover, a general mathematical function has been applied to the experimental data; this could be appropriate for adequately describing material settling patterns and offers practical parameters for characterizing starch powders within the context of a pharmaceutical quality system.

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.

Diagnosis and treatment of acute pancreatitis: the position statement of the Italian Association for the study of the pancreas.

This medical position statement has been developed by the board of ProInf AISP (Computerized Project on Acute Pancreatitis) Study Group. The evidence and key recommendations were discussed at a dedicated meeting held in Milan on September 2007 and during this meeting the main clinical and therapeutic medical topics were extensively discussed. Each of the proposed recommendations was discussed and an initial consensus was reached. Acute pancreatitis in Italy is a disease of increasing annual incidence. The diagnosis of the disease should be established within 48hours of admission. Early identification of patients at risk of developing a severe attack of acute pancreatitis is of great importance because rapid therapeutic interventions improve outcome. The endoscopic approach seems to be most beneficial measure in patients with acute pancreatitis with jaundice and in those with cholangitis. The development of infected necrosis should be assessed using fine-needle aspiration and the sample should be cultured for germ isolation and characterization. The role of early ERCP in all patients with severe acute pancreatitis of biliary origin is still controversial. The data supporting the efficacy of antibiotic prophylaxis to prevent infection of necrosis are conflicting. The refeeding is a crucial topic in patients who have recovered from an acute episode of mild acute pancreatitis, but there are very few studies on this issue.

Diagnostic assessment and outcome of acute pancreatitis in Italy: results of a prospective multicentre study. ProInf-AISP: Progetto informatizzato pancreatite acuta, Associazione Italiana Studio Pancreas, phase II.

BACKGROUND AND AIM: Up till now, only one study providing practically complete information on acute pancreatitis in Italy has been published. The aim of this prospective study was to evaluate the clinical characteristics, in terms of diagnostic assessment and outcome, of a large series of patients affected by acute pancreatitis in Italy. MATERIALS AND METHODS: The study involved 56 Italian centres, homogeneously distributed throughout the entire national territory. Each participating centre was furnished with an ad hoc software including 530 items along with subsequent collection, tabulation and quality control of the data. RESULTS: One thousand five hundred and forty case report forms of patients affected by acute pancreatitis were collected but 367 of them (24%) were subsequently eliminated from the final analysis. Therefore, 1173 patients (581 females and 592 males) were recruited. Mean age of patients was 62.0+/-18.2 years (95% confidence interval, 60.9-63.0). On the basis of Atlanta classification, 1006 patients (85.8%) were defined as mild and 167 (14.2%) as severe pancreatitis. Biliary forms represented the most frequent aetiological category (813 cases, 69.3%) while alcoholic forms only 6.6% (77 cases); the remaining aetiologies accounted for 7.1% (83 cases) while 200 cases (17.1%) remained without a definite aetiological factor. Complete recovery was achieved in 1016 patients (86.6%) whereas morphological sequelae were found in 121 patients (10.3%) and mortality in 36 patients (3.1%; 0.4% in mild and 19.2% in severe acute pancreatitis). Ultrasonography was largely utilised as a first line diagnostic tool in all patients, with valuable visualisation of the pancreas in 85% of patients. Computer tomography scan was also widely used, with 66.7% of exams in mild and 33.3% in severe pancreatitis. Patients affected by biliary pancreatitis presented more severe (p=0.004) and necrotizing forms (p=0.021). Mortality was significantly related (p<0.001) with the extension of pancreatic necrosis and with an age of over 70 years. Body mass index presented significantly greater values in severe than in mild forms (p<0.001). CONCLUSIONS: Association of creatinine serum level over 2mg/dl with an abnormal chest X-ray showed a high significant correlation with a more severe outcome in terms of morphological sequelae and mortality (p=0.0001). Acute pancreatitis in Italy more commonly presents biliary aetiology and favourable outcome with low rate of complications and mortality. From a cost-effectiveness standpoint, diagnostic approach to this disease needs to be better standardised.

A prospective multicentre survey on the treatment of acute pancreatitis in Italy.

BACKGROUND: The Italian Association for the Study of the Pancreas released a diagnostic and therapeutic algorithm for acute pancreatitis in 1999. AIM: This study focused on the analysis of the therapeutic approach for the treatment of acute pancreatitis in Italy. PATIENTS: One thousand, one hundred and seventy-three patients were recruited: 1006 patients (85.8%) had mild acute pancreatitis (MAP) and 167 (14.2%) had the severe acute pancreatitis (SAP); 161 patients showed pancreatic necrosis at computed tomography; 121 patients (10.3%) had sequelae and 36 (3.1%) died. RESULTS: Non-steroidal anti-inflammatory drugs and tramadol were used more frequently in patients with the MAP whereas opioids and the association schedules were used more frequently in patients with the SAP (P<0.001). Gabexate mesilate was utilised in 831 out of 1173 patients (70.8%); in particular, gabexate mesilate was used in 70.6% patients with MAP and in 73.1% of those with SAP (P=0.521). The duration of the drug administration was significantly shorter in those having MAP than in those having the SAP (P<0.001). The antibiotics most frequently used for the prophylaxis against infection from pancreatic necrosis (43.1%) were carbapenems. Only a small number of patients received enteral nutrition (4.7%). Endoscopic retrograde cholangiopancreatography was carried out in 344 of the 1173 patients (29.3%). Surgery was performed in 48 with SAP (19 had elective biliary surgery and 29 had pancreatic surgery). CONCLUSIONS: The results of this survey indicate a lack of compliance with the guidelines which regard the indications mainly for interventional endoscopy and surgery.

Same-day endoscopic retrograde cholangiopancreatography after transduodenal endoscopic ultrasound-guided needle aspiration: do we need to be cautious?

Patients who are undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for suspected pancreatic tumors frequently undergo endoscopic retrograde cholangiopancreatography (ERCP) for palliation of their symptoms. Performing EUS-FNA and ERCP in tandem may be cost-effective and may reduce procedure time, but the potential risks associated with this approach have not been clearly defined in the literature. We report two patients who underwent same-day therapeutic ERCP after transduodenal EUS-FNA for pancreatic tumors. Endoscopic biliary manipulation during ERCP aggravated an inadvertent and subclinical needle puncture injury to the bile duct sustained during the preceding EUS-FNA. This resulted in leakage of bile into the retroperitoneal space, and both patients required laparotomy and surgical drainage. Additional clinical evidence is needed to clarify these issues and to determine whether it would be prudent to perform therapeutic ERCP prior to diagnostic transduodenal EUS-FNA when these two procedures are planned as sequential or same-day procedures.

Multiple stenting of refractory pancreatic duct strictures in severe chronic pancreatitis: long-term results.

BACKGROUND AND STUDY AIMS: Dominant pancreatic duct strictures located in the head of the pancreas in patients with severe chronic pancreatitis are often managed by endoscopic placement of a single plastic stent. Patients with refractory strictures after prolonged stenting require repeated stent replacement or surgical pancreaticojejunostomy. Placement of multiple plastic stents has proved effective in managing postoperative biliary strictures. The aim of this study was to investigate the feasibility, efficacy, and long-term results of multiple stenting of refractory pancreatic strictures in severe chronic pancreatitis. PATIENTS AND METHODS: 19 patients with severe chronic pancreatitis (16 men, three women; mean age 45 years) and with a single pancreatic stent through a refractory dominant stricture in the pancreatic head underwent the following protocol: (i) removal of the single pancreatic stent; (ii) balloon dilation of the stricture; (iii) insertion of the maximum number of stents allowed by the stricture tightness and the pancreatic duct diameter; and (iv) removal of stents after 6 to 12 months. RESULTS: The median number of stents placed through the major or minor papilla was 3, with diameters ranging from 8.5 to 11.5 Fr and length from 4 to 7 cm. Only one patient (5.5 %) had persistent stricture after multiple stenting. During a mean follow-up of 38 months after removal, 84 % of patients were asymptomatic, and 10.5 % had symptomatic stricture recurrence. No major complications were recorded. CONCLUSION: Endoscopic multiple stenting of dominant pancreatic duct strictures in chronic pancreatitis is a feasible and safe technique. Multiple pancreatic stenting is promising in obtaining persistent stricture dilation on long-term follow-up in the setting of severe chronic pancreatitis.

Effect of endoscopic augmentation of the lower oesophageal sphincter (Gatekeeper reflux repair system) on intraoesophageal dynamic characteristics of acid reflux.

BACKGROUND AND AIMS: Improvements in symptoms following endoscopic procedures for gastro-oesophageal reflux disease (GORD) are seldom supported by normalisation of acid exposure time at the distal oesophagus. However, the distribution of gastric acid within the proximal oesophagus is a main determinant of symptom generation in GORD patients. In this study, our aim was to assess the effect of endoscopic insertion of hydrogel expandable prostheses into the oesophageal submucosa on spatiotemporal characteristics of gastro-oesophageal reflux. METHODS: Oesophageal manometry and multichannel ambulatory 24 hour pH monitoring were carried out in nine patients before and six months after the endoscopic procedure. Dynamic characteristics of gastro-oesophageal reflux in patients were also compared with those in 13 asymptomatic controls. RESULTS: Acid exposure time (AET) at the distal oesophagus decreased from 11.7% (95% confidence interval 6.1-21.8) at baseline to 7.7% (3.7-11.6) at follow up (NS). Of the nine patients, distal AET normalised in three. AET at the middle (7.6% (2.9-12.3)) and proximal (2.4% (0.1-4.8)) oesophagus decreased significantly in all patients (2.4% (0.3-4.5), p <0.01; 1.2% (0.2-2.2), p<0.05 respectively). Proximal extent of acid events significantly decreased in all patients at follow up (37.3% v 9.5%), reaching values observed in asymptomatic controls. Median GORD health related quality of life scores significantly improved from 35.5 at baseline to 9.4. CONCLUSIONS: Despite the lack of a significant improvement in traditional pH variables, endoscopic implant of hydrogel prostheses above the lower oesophageal sphincter significantly decreases proximal spread of acid reflux into oesophageal body. This effect would explain the improvement in symptoms in patients six months after therapy.

Endoscopic augmentation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease: multicenter study of the Gatekeeper Reflux Repair System.

BACKGROUND AND STUDY AIMS: The safety and effectiveness of the Gatekeeper Reflux Repair System (Medtronic Europe, Tolochenaz, Switzerland) in the treatment of gastroesophageal reflux disease (GERD) was evaluated. This new, reversible treatment modality involves the endoscopic introduction of expandable polyacrylonitrile-based hydrogel prostheses into the esophageal submucosa to augment the lower esophageal sphincter (LES). PATIENTS AND METHODS: For this study, data from two prospective, nonrandomized European multicenter trials were pooled. Sixty-nine GERD patients with heartburn and regurgitation and abnormal esophageal acid exposure (24-h pH < 4.0 for > 4 % of the total time) who had responded to proton-pump inhibitor (PPI) therapy were recruited, and 68 were treated with up to six prostheses placed at the gastroesophageal junction. Patients underwent esophageal manometry, endoscopy, 24-h pH-metry, and symptom scoring at intake and 1, 3, and 6 months after the procedure. RESULTS: A total of 77 procedures were performed in 67 patients, and a total of 270 prostheses were placed (mean 4.3 per procedure). At 1 and 6 months, 80.4 % and 70.4 % of the prostheses were retained, respectively. At 6 months, 24-h pH-metry outcomes with pH < 4.0 for > 4.0 % of the time decreased from 9.1 % to 6.1 % (n = 45; P < 0.05). Median LES pressure increased significantly from 8.8 mmHg at baseline to 13.8 mmHg at 6 months (n = 42, P < 0.01). Median GERD heartburn-related quality-of-life scores improved significantly from 24.0 to 5.0 (n = 53, P < 0.01) in patients no longer receiving PPI therapy. Two serious adverse events (3.0 %) occurred. Both patients recovered uneventfully. Prostheses were endoscopically removed from one patient without any adverse events. CONCLUSIONS: The Gatekeeper Reflux Repair System is a safe endoscopic treatment modality that significantly improves GERD symptoms and has objective effects on acid reflux.

Prospective multicentre survey on acute pancreatitis in Italy (ProInf-AISP): results on 1005 patients.

BACKGROUND AND AIM: Till now, no Italian studies providing information on acute pancreatitis have been published. The aim of this study was to evaluate the epidemiological and clinical characteristics of acute pancreatitis in Italy. MATERIALS AND METHODS: The study involved 37 Italian centres distributed homogeneously throughout the entire national territory and prospectively collected epidemiological, anamnestic, laboratory, radiological, therapeutic (pharmacological, endoscopic and surgical) data, relevant to each individual case of acute pancreatitis consecutively observed during the period from September 1996 to June 2000. RESULTS: One thousand two hundred and six case report forms were collected, but 201 patients (16.6%) were subsequently eliminated from the final analysis. We therefore studied 1005 patients, 533 (53%) males and 472 (47%) females, mean age 59.6 +/- 20 years. On the basis of the Atlanta classification of acute pancreatitis, 753 patients of the 1005 cases analysed (75%) were mild and 252 patients (25%) severe. The aetiology was biliary in 60% of the patients, related to alcohol abuse in 8.5%, while in 21% of the cases it could not be identified. Over 80% of the patients (83%) were admitted to hospital within 24 h from the onset of clinical symptoms, while only 6% were admitted after 48 h. In particular, 65% of the patients were admitted to hospital within the first 12 h. Antibiotics were used in 85% of the severe and 75% of mild forms. Endoscopic therapy was carried out in 65% of the severe cases, but only in 40% it was carried out prior to 72 h. Eighty-five patients (8.5% of the total, 34% of the severe forms) underwent surgical intervention: 20% on the first day, 38.5% within the fourth day, and the remaining (41.5% of the cases) later on for infected necrosis. The mean duration of hospitalisation for patients with mild pancreatitis was 13 +/- 8 days, while for the severe disease it was of 30 +/- 14 days. The overall mortality rate was 5%, 17% in severe and 1.5% in mild pancreatitis. CONCLUSIONS: Acute pancreatitis in Italy is more commonly a mild disease with a biliary aetiology. The treatment of the disease is not optimal and, on the basis of these data, needs to be standardised. Despite this, the overall mortality rate is low (5%).

Gastrointestinal motor dysfunction, symptoms, and neuropathy in noninsulin-dependent (type 2) diabetes mellitus.

Although relatively frequent. diabetic involvement of digestive tract motility has not been investigated extensively in different organs. The authors studied esophageal, gastric, and gallbladder motor function in 35 type 2 (noninsulin-dependent) diabetic patients to determine the extent of gut involvement. Of these patients, 27 (77%) had peripheral neuropathy, 12 (34%) had both peripheral and autonomic neuropathy, and 22 (63%) had gastrointestinal symptoms. Esophageal manometric abnormalities were recorded in 18 patients, and delayed radionuclide emptying of the esophagus was documented in 16 patients, with a 83% concordance between the two tests. Scintigraphic gastric emptying of solids was delayed in 56% of patients, whereas gallbladder emptying after cholecystokinin stimulation was reduced in 69% of them. In 74% of patients at least one of the viscera under investigation showed abnormal motor function; however, only 36% of patients displayed involvement of the three organs. Gastrointestinal symptoms, duration and therapy of diabetes, previous poor glycemic control, and retinopathy did not correlate with the presence or the extent of motor disorders. Neuropathy was not predictive of gastrointestinal involvement and its extent; however, when motor abnormalities were present in patients with neuropathy, these were usually more severe. Gastrointestinal motor disorders are frequent and widespread in type 2 diabetics, regardless of symptoms. Autonomic neuropathy has a poor predictive value on motor disorders (0.75 for the esophagus, 0.5 for the stomach, 0.8 for the gallbladder), thus suggesting the coexistence of other pathophysiologic mechanisms.

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.

[Results of endoscopic biliary drainage in primary tumors of the common bile duct (cholangiocarcinoma)]. / Risultati del drenaggio biliare endoscopico nei tumori primitivi della via biliare principale (colangiocarcinomi).

Endoscopic drainage is an effective therapy for palliation of patients with bile duct carcinoma. From November 1987 to November 1994 112 patients with cholangiocarcinoma were observed. The success rate of the procedure was 94.5%. The biliary drainage was successful in 99% of patients (in 4% of patients the complete biliary drainage was obtained with the aid of a transhepatically inserted guide-wire with the "rendez-vous" procedure). In 15 patients an intraluminal radiation therapy with Iridium-192 was associated. The morbility was 13% and the 30-days mortality 11%. A surgical operation was performed in 26% of patients with radical intent. The mean survival time in patients treated only endoscopically was 208 days for patients with lesions of the distal and middle third of the bile duct and 281 days for patients with hilar cholangiocarcinoma. In patients with intraluminal radiation therapy the mean survival time was 357 days, with a significative difference with the only endoscopically treated group (357 vs 238 days, p < 0.05). We conclude that endoscopic drainage is a safe and effective management for patients with cholangiocarcinoma and it does not preclude definitive surgical treatment in appropriate candidate.

Treatment of "obstructive" pain by endoscopic drainage in patients with pancreatic head carcinoma.

Obstruction of the main pancreatic duct with secondary upstream ductal hypertension is one cause of pain in patients with pancreatic cancer. Pancreatic endoscopic stenting and decompression of the pancreatic duct have been effective in the treatment of pain secondary to chronic calcifying pancreatitis and in one case of pancreatic cancer. We describe eight patients with unresectable cancer of the pancreatic head associated with upstream dilatation of the pancreatic duct and severe pancreatic "obstructive"-type pain (correlation with meals and pain radiation to the back) in which a pancreatic stent was inserted across the neoplastic stricture. No mortality was associated with the procedure. All patients but one were free of pain within 48 hours after endoscopic pancreatic stenting, and all discontinued narcotics. Mean survival time was 165.5 days (range, 26 to 575 days). Six patients were still without symptoms, whereas two had a painful relapse a few days before death. No clinical evidence of pancreatic clogged stent was observed during follow-up. Endoscopic pancreatic drainage is a safe and effective way of controlling cancer pain in selected cases and should be considered as a further therapeutic option in these patients.