Urban Arnelo

Intramuscular Autotransplantation of Pancreatic Islets in a 7‐Year‐Old Child: A 2‐Year Follow‐Up

A 7‐year‐old girl with severe hereditary pancreatitis underwent total pancreatectomy. A total of 160 000 islet equivalents (6400 islet/kg) were transplanted to the brachioradialis muscle of the right forearm. Her plasma C‐peptide level was undetectable after pancreatectomy but increased to 1.37 ng/mL after 17 days; at this time point, her insulin requirement was 0.75 units of insulin/kg/day. At 5‐ and 27‐months, her hemoglobin A1c (HbA1c) and insulin requirements were 4.5 and 5.3% and 0.3 and 0.18 units/kg/day, respectively. Basal and stimulated C‐peptide levels were 0.67 ± 0.07 and 3.36 ± 1.37 ng/mL, respectively. Stimulated insulin levels were 30% higher in the islet‐bearing arm compared to the contralateral arm after glucagon stimulation. After surgery and islet transplantation, the quality of life improved dramatically and she gained 8 kg of weight. In summary, a normal HbA1c, a low insulin requirement and the absence of recurrent hypoglycemia and the gradient of insulin between the arms indicate that the intramuscularly transplanted islets contribute to a long‐term clinically significant metabolic control.

Intraoperative endoscopic retrograde cholangiopancreatography (ERCP) to remove common bile duct stones during routine laparoscopic cholecystectomy does not prolong hospitalization: a 2-year experience

Background: There is still some controversy regarding the optimal timing and best method for the removal of common bile duct stones (CBDS). Intraoperative endoscopic retrograde cholangiopancreaticography (IO-ERCP) is an alternative method that should be considered for this procedure. The aim of our study was to investigate the clinical outcome of a single-step procedure (IO-ERCP) to remove CBDS, thereby combining two existing high-volume clinical modalities—i.e., laparoscopic cholecystectomy (LC) and ERCP. Methods: Between January 2000 and December 2001, 674 patients, 192 male and 482 female, underwent cholecystectomy at our hospital. Therewere 612 LC (90.8%), 37 converted procedures (5.5%), and 25 open operations (3.7%). In 592 of the patients, (87.8%) intraoperative cholangiography (IOC) was performed. In 34 (5.7%) of those who had and IOC, an IO-ERCP was performed. While the surgeon waited for the endoscopist, care was taken to introduce a thin guidewire through the lOC catheter and pass it through the sphincter of Oddi, out into the duodenum. This complementary procedure greatly facilitated the subsequent cannulation of the bile ducts. Results: The cannulation frequency of the CBD was 100%. Common bile duct stones were successfully extracted in 93.5%. Endoscopic sphincterotomy (EST), followed by the insertion of a plastic endoprosthesis, was performed in two patients with remaining stones. The CBD of these two patients was cleared by postoperative ERCP. None of the patients developed postoperative pancreatitis. The operating time was prolonged as compared with the time for LC (192 vs 110 mins; p < 0.05). The length of hospitalization for IO-ERCP patients did not differ from that for patients undergoing cholecystectomy alone (2.6 vs 2.1. days; NS). Conclusions: The study suggests that elective IO-ERCP is a safe and efficient method for removing CBDS that has a low risk of inducing postoperative pancreatitis and does not prolong postoperative hospitalization. This technique enables perioperative extraction of CBDS without open or laparoscopic surgical exploration of the CBD and can be used safely in a routine clinical setting.

Nationwide, population-based data from 11,074 ERCP procedures from the Swedish Registry for Gallstone Surgery and ERCP

BACKGROUND The Swedish Registry for Gallstone Surgery and ERCP (GallRiks) is the first nationwide Web-based quality registry for gallstone surgery and ERCP in the world. In this article we report data from 11,074 ERCPs performed in 2007 and 2008. OBJECTIVE The aim of this study is to present outcomes, safety data, and success rates of ERCPs performed in Sweden. DESIGN Data gathering from a medical record database. PATIENTS This study reviewed 11,074 ERCPs performed in 2007 and 2008. METHODS In GallRiks, data concerning surgery performed for gallstone disease as well as all ERCPs are recorded. The registry is approved by the Swedish Surgical Society and is based on an Internet platform with online data registration. The online program includes 30-day follow-up information as well as the opportunity to retrieve electronic reports on demand. The present data represent 76% of all ERCPs performed in Sweden in 2007 and 95% of those performed in 2008. The database also has been validated, indicating a complete match between the medical records and the database in 97.3% of ERCP cases. MAIN OUTCOME MEASUREMENTS Cannulation success and perioperative and postoperative complications. RESULTS A successful bile duct cannulation was achieved in 92% of the ERCPs performed. The presence of common bile duct stones was the predominant finding and was seen in 36.8% of examinations. Perioperative and postoperative complication rates were 2.5% and 9.8%, respectively. The rate of ERCP-induced pancreatitis was 2.7%, and the total 30-day mortality rate in the database was 5.9% but varied significantly among the different diagnostic groups. The indications for ERCP differed between high-volume and low-volume centers, indicating an adequate referral pattern of complex cases in Sweden. LIMITATIONS GallRiks registration is voluntary and thus not 100%. This makes selection bias a possibility. CONCLUSION ERCP is widely used at Swedish hospitals, with acceptable cannulation success rates and perioperative and postoperative complication rates similar to established standards. GallRiks is a population-based nationwide registry with good data validity and high inclusion rates regarding ERCPs.

The effect of prophylactic transpapillary pancreatic stent insertion on clinically significant leak rate following distal pancreatectomy: results of a prospective controlled clinical trial.

Objective:To determine whether prophylactic pancreatic duct stenting reduces pancreatic fistula (PF) formation after distal pancreatectomy (DP). Background:PF causes major morbidity after DP. Transpapillary pancreatic stenting has been proposed to be beneficial in treating established PF and also, prophylactically, to reduce the risk for PF after DP. Patients and Methods:Patients scheduled for DP during October 2006 to December 2010 were assessed and, if eligible, randomized to DP without (DP) or with stenting before transection of the neck of the gland (DP + stent). DP procedure was standardized and the follow-up period included the first 30 postoperative days. The outcomes were assessed according to the intention to treat analysis principle. Results:Sixty-four patients were assessed and 58 were randomized to either DP (n = 29) or DP + stent (n = 29). Mean ± SD operation time for DP was 218.8 ± 94.1 compared to 283.3 ± 131.9 for DP + stent (P = 0.052). Clinically significant PF (ISGPF [The International Study Group on Pancreatic Fistula] classification Grade B or C) occurred in 6 DP (22.2%) and 11 (42.3%) DP + stent patients (odds ratio: 2.57, 95% confidence interval 0.78–8.48; P = 0.122). The mean hospital stay for patients without stent was 13.4 ± 6.4 days compared to 19.4 ± 14.4 days for those provided with a pancreatic stent (P = 0.071). Conclusions:The results from this trial show that prophylactic pancreatic stenting does not reduce PF when performing a standardized resection of the body and tail of the pancreas. The trial was registered at clinicaltrials.gov NCT00500968.

An antireflux stent versus conventional stents for palliation of distal esophageal or cardia cancer: a randomized clinical study

BackgroundSelf-expandable metal stents placed across the esophagogastric junction for palliative treatment of malignant strictures may lead to gastroesophageal reflux and pulmonary aspiration. This study compared the effects of a Dua antireflux stent with those of a conventional stent.MethodsPatients with incurable cancer of the distal esophagus or gastric cardia were randomly assigned to receive an antireflux stent (n = 19) or a standard stent (n = 22) at nine Swedish hospitals during the period September 1, 2003 to July 31, 2005. Complications were recorded at clinical follow-up visits. Survival rates were assessed through linkage to the Population Register. Dysphagia, reflux symptoms, esophageal pain, dyspnea, and global quality of life were assessed as changes in mean scores between baseline and 1 month after stent insertion through validated questionnaires.ResultsNo technical problems occurred during stent placement in the 41 enrolled patients. Fewer patients with complications were observed in the antireflux stent group (n = 3) than in the standard group (n = 8), but no statistically significant difference was shown (p = 0.14). The survival rates were similar in the two groups (p = 0.99; hazard ratio, 1.0; 95% confidence interval, 0.5–2.0). The groups did not differ significantly in terms of studied esophageal or respiratory symptoms or quality of life. Clinically relevant improvement in dysphagia occurred in both groups. Dyspnea decreased after antireflux stent insertion (mean score change, –11), and increased after insertion of standard stent (mean score change, +21).ConclusionsAntireflux stents may be used without increased risk of complications, mortality, esophageal symptoms, or reduced global quality of life. These results should encourage large-scale randomized trials that can establish potentially beneficial effects of antireflux stents.

Sufficiency of postprandial plasma levels of islet amyloid polypeptide for suppression of feeding in rats

Our objective was to study whether islet amyloid polypeptide (IAPP) produces satiety by an endocrine mechanism. We used a rat model to determine whether postprandial plasma levels of IAPP are comparable to those required to inhibit feeding when IAPP is administered by continuous intravenous infusion. Food intake in rats with aortic catheters increased plasma IAPP levels from a fasting level of 10.8 ± 0.5 pM to a peak level of 19.0 ± 1.0 pM at 2.2 ± 0.5 h. In rats with jugular vein and aortic catheters, the threshold intravenous dose for IAPP suppression of feeding was between 1 and 3 pmol ⋅ kg-1 ⋅ min-1. The 3 pmol ⋅ kg-1 ⋅ min-1dose decreased 4-h intake by ∼25% by decreasing meal frequency rather than meal size. This dose increased plasma IAPP by ∼24 pM. These results suggest that postprandial plasma levels of IAPP are not quite sufficient to independently produce satiety.

Skeletal muscle insulin resistance after trauma: insulin signaling and glucose transport

Surgical trauma induces peripheral insulin resistance; however, the cellular mechanism has not been fully elucidated. We examined the effects of surgical trauma on insulin receptor signaling and glucose transport in skeletal muscle, a tissue that plays a predominant role in maintaining glucose homeostasis. Surgical trauma was induced by intestinal resection in the rat. Receptor phosphorylation was not altered with surgical trauma. Phosphotyrosine-associated phosphatidylinositol (PI) 3-kinase association was increased by 60 and 82% compared with fasted and fed controls, respectively (P < 0. 05). Similar results were observed for insulin receptor substrate-1-associated PI 3-kinase activity. Insulin-stimulated protein kinase B (Akt kinase) phosphorylation was increased by 2.2-fold after surgical trauma (P < 0.05). The hyperphosphorylation of Akt is likely to reflect amplification of PI 3-kinase after insulin stimulation. Submaximal rates of insulin-stimulated 3-O-methylglucose transport were reduced in trauma vs. fasted rats by 51 and 38% for 100 and 200 microU/ml of insulin, respectively (P < 0.05). In conclusion, insulin resistance in skeletal muscle after surgical trauma is associated with reduced glucose transport but not with impaired insulin signaling to PI 3-kinase or its downstream target, Akt. The surgical trauma model presented in this report provides a useful tool to further elucidate the molecular mechanism(s) underlying the development of insulin resistance after surgical trauma.Surgical trauma induces peripheral insulin resistance; however, the cellular mechanism has not been fully elucidated. We examined the effects of surgical trauma on insulin receptor signaling and glucose transport in skeletal muscle, a tissue that plays a predominant role in maintaining glucose homeostasis. Surgical trauma was induced by intestinal resection in the rat. Receptor phosphorylation was not altered with surgical trauma. Phosphotyrosine-associated phosphatidylinositol (PI) 3-kinase association was increased by 60 and 82% compared with fasted and fed controls, respectively ( P < 0.05). Similar results were observed for insulin receptor substrate-1-associated PI 3-kinase activity. Insulin-stimulated protein kinase B (Akt kinase) phosphorylation was increased by 2.2-fold after surgical trauma ( P < 0.05). The hyperphosphorylation of Akt is likely to reflect amplification of PI 3-kinase after insulin stimulation. Submaximal rates of insulin-stimulated 3- O-methylglucose transport were reduced in trauma vs. fasted rats by 51 and 38% for 100 and 200 μU/ml of insulin, respectively ( P< 0.05). In conclusion, insulin resistance in skeletal muscle after surgical trauma is associated with reduced glucose transport but not with impaired insulin signaling to PI 3-kinase or its downstream target, Akt. The surgical trauma model presented in this report provides a useful tool to further elucidate the molecular mechanism(s) underlying the development of insulin resistance after surgical trauma.

Endoscopic Sphincterotomy and Risk of Malignancy in the Bile Ducts, Liver, and Pancreas

BACKGROUND & AIMS After endoscopic sphincterotomy (ES), an elevated long-term risk of cholangiocarcinoma has been reported. However, large population-based studies testing this hypothesis are lacking. The aim of this study was to evaluate the risk in a large population-based cohort. METHODS Data concerning all patients having had an inpatient endoscopic retrograde cholangiopancreatography (ERCP) were collected from the Swedish Hospital Discharge Register. Incident cases of malignancy were identified through linkage to the Swedish Cancer Registry. Patients with a diagnosis of malignancy before or within 2 years of the ERCP were excluded. The cohort was followed to a diagnosis of malignancy, censoring as a result of death, emigration, or end of follow-up. The risk of malignancy was calculated as standardized incidence ratio (SIR) compared with the general population, inherently adjusting for age, gender, and year of entry. RESULTS A total of 27,708 patients undergoing ERCP from 1976 through 2003 for benign disease were included in the cohort. ES was performed in 11,617 of these. The risk of malignancy in the bile ducts alone and in the bile ducts, liver, and pancreas together was significantly elevated in the total cohort (SIR, 3.3; 95% confidence interval, 2.3-4.5), irrespective of whether an ES was performed. The risk of malignancy diminished with increasing follow-up time. Patients ever having had a cholecystectomy had a significantly lower risk of the studied malignancies. CONCLUSIONS The risk of malignancy in the bile ducts, liver, or pancreas is elevated after ERCP in benign disease. However, ES does not seem to affect this risk.

Chronically Administered Islet Amyloid Polypeptide in Rats Serves as an Adiposity Inhibitor and Regulates Energy Homeostasis

Aims/Hypothesis: Islet amyloid polypeptide (IAPP) reduces food intake and body weight in laboratory animals. In addition, IAPP appears to regulate nutrient metabolism. In the present studies, we investigated the effect of chronic IAPP treatment on different aspects of energy homeostasis. Methods: IAPP was infused (25 pmol/kg/min) from subcutaneous osmotic pumps for 2–7 days. Rats in 2 saline-infused control groups were fed ad libitum (AF) or pair-fed (PF) against the IAPP-treated rats. Results: As expected, the IAPP infusion reduced food intake and body weight gain. In addition, the IAPP treatment decreased the epididymal fat pad (vs. PF rats, p < 0.05) and lowered circulating levels of triglycerides (vs. PF rats, p < 0.05), free fatty acids (vs. PF rats, p < 0.05), leptin (vs. both AF and PF rats, p < 0.05) and insulin (vs. AF rats, p < 0.05). In contrast, glucose and protein metabolism in the IAPP-treated rats was largely unchanged, as shown in results regarding serum glucose, glucose transport in skeletal muscle, blood urea nitrogen, and glycogen and protein content in the liver and in skeletal muscle. Conclusion/Interpretation: In summary, chronic IAPP exposure led to a changed lipid metabolism, which was characterized by decreased adiposity, hypolipidemia and hypoleptinemia, and to unchanged glucose and protein homeostasis. These results were similar to those seen in rodents during chronic exposure to another satiety/adiposity regulator, leptin. In conclusion, chronically administered IAPP plays a role as a satiety and adiposity signal in rats, and helps regulate energy homeostasis.

Difficult cannulation as defined by a prospective study of the Scandinavian Association for Digestive Endoscopy (SADE) in 907 ERCPs

Abstract Background. The definition of a “difficult” cannulation varies considerably in reports of endoscopic retrograde cholangiopancreatography (ERCP). Aims. To define a difficult cannulation, which translates into higher risk of post-ERCP pancreatitis. Patients and methods. Prospective consecutive recording of 907 cannulations in Scandinavian centers done by experienced endoscopists. Inclusion: indication for biliary access in patients with intact papilla. Exclusion: acute non-biliary and chronic pancreatitis at time of procedure. Results. The primary cannulation succeeded in 74.9%, with median values for time 0.88 min (53 s), with two attempts and with zero pancreatic passages or injections. The overall cannulation success was 97.4% and post-ERCP pancreatitis (PEP) rate was 5.3%. The median time for all successful cannulations was 1.55 min (range 0.02–94.2). If the primary cannulation succeeded, the pancreatitis rate was 2.8%; after secondary methods, it rose to 11.5%. Procedures lasting less than 5 min had a PEP rate of 2.6% versus 11.8% in those lasting longer. With one attempt, the PEP rate was 0.6%, with two 3.1%, with three to four 6.1%, and with five and more 11.9%. With one accidental pancreatic guide-wire passage, the risk of the PEP was 3.7%, and with two passages, it was 13.1%. Conclusions. If the increasing rate of PEP is taken as defining factor, the wire-guided cannulation of a native papilla can be considered difficult after 5 min, five attempts, and two pancreatic guide-wire passages when any of those limits is exceeded.