Oliver Mann

Peroral Endoscopic Myotomy for the Treatment of Achalasia: A Prospective Single Center Study

OBJECTIVES:Endoscopic balloon dilatation and laparoscopic myotomy are established treatments for achalasia. Recently, a new endoscopic technique for complete myotomy was described. Herein, we report the results of the first prospective trial of peroral endoscopic myotomy (POEM) in Europe.METHODS:POEM was performed under general anesthesia in 16 patients (male:female (12:4), mean age 45 years, range 26–76). The primary outcome was symptom relief at 3 months, defined as an Eckhard score ≤3. Secondary outcomes were procedure-related adverse events, lower esophageal sphincter (LES) pressure on manometry, reflux symptoms, and medication use before and after POEM.RESULTS:A 3-month follow-up was completed for all patients. Treatment success (Eckhard score ≤3) was achieved in 94% of cases (mean score pre- vs. post-treatment (8.8 vs. 1.4); P<0.001). Mean LES pressure was 27.2 mm Hg pre-treatment and 11.8 mm Hg post-treatment (P<0.001). No patient developed symptoms of gastro-esophageal reflux after treatment, but one patient was found to have an erosive lesion (LA grade A) on follow-up esophagogastroduodenoscopy. No patient required medication with proton pump inhibitors or antacids after POEM.CONCLUSIONS:POEM is a promising new treatment for achalasia resulting in short-term symptom relief in >90% of cases. Studies evaluating long-term efficacy and comparing POEM with established treatments have been initiated.

Long-term Follow-up of a Randomized Trial Comparing the Beger and Frey Procedures for Patients Suffering From Chronic Pancreatitis

Objective:To report on the long-term follow-up of a randomized clinical trial comparing pancreatic head resection according to Beger and limited pancreatic head excision combined with longitudinal pancreatico-jejunostomy according to Frey for surgical treatment of chronic pancreatitis. Summary Background Data:Resection and drainage are the 2 basic surgical principles in surgical treatment of chronic pancreatitis. They are combined to various degrees by the classic duodenum preserving pancreatic head resection (Beger) and limited pancreatic head excision combined with longitudinal pancreatico-jejunostomy (Frey). These procedures have been evaluated in a randomized controlled trial by our group. Long-term follow up has not been reported so far. Methods:Seventy-four patients suffering from chronic pancreatitis were initially allocated to DPHR (n = 38) or LE (n = 36). This postoperative follow-up included the following parameters: mortality, quality of life (QL), pain (validated pain score), and exocrine and endocrine function. Results:Median follow-up was 104 months (72-144). Seven patients were not available for follow-up (Beger = 4; Frey = 3). There was no significant difference in late mortality (31% [8/26] versus 32% [8/25]). No significant differences were found regarding QL (global QL 66.7 [0–100] versus 58.35 [0–100]), pain score (11.25 [0–75] versus 11.25 [0–99.75]), exocrine (88% versus 78%) or endocrine insufficiency (56% versus 60%). Conclusions:After almost 9 years’ long-term follow-up, there was no difference regarding mortality, quality of life, pain, or exocrine or endocrine insufficiency within the 2 groups. The decision which procedure to choose should be based on the surgeons experience.

Resection vs drainage in treatment of chronic pancreatitis: long-term results of a randomized trial.

BACKGROUND & AIMS Tailored organ-sparing procedures have been shown to alleviate pain and are potentially superior in terms of preservation of endocrine and exocrine function as compared with standard resection (Whipple) for chronic pancreatitis with inflammatory pancreatic head tumor. Long-term results comparing these 2 procedures have not been published so far. The aim of this study was to report on long-term results of a randomized trial comparing a classical resective procedure (pylorus-preserving Whipple) with an extended drainage procedure (Frey) for chronic pancreatitis. METHODS All patients who participated in a previously published randomized trial on the perioperative course comparing both procedures were contacted with a standardized, validated, quality of life and pain questionnaire. Additionally, patients were seen in the outpatient clinic to assess endocrine and exocrine pancreatic function by an oral glucose tolerance test and fecal chymotrypsin test. RESULTS There were no differences between both groups regarding quality of life, pain control, or other somatic parameters after a median of 7 years postoperatively. Correlations among continuous alcohol consumption, endocrine or exocrine pancreatic function, and pain were not found. CONCLUSIONS Both procedures provide adequate pain relief and quality of life after long-term follow-up with no differences regarding exocrine and endocrine function. However, short-term results favor the organ-sparing procedure.

Is the Whipple procedure harmful for long-term outcome in treatment of chronic pancreatitis? 15-years follow-up comparing the outcome after pylorus-preserving pancreatoduodenectomy and Frey procedure in chronic pancreatitis.

Objective:The aim of this study was to report on 15-year long-term results of a randomized controlled trial comparing extended drainage procedure (Frey) and classical resectional procedure [pylorus-preserving pancreatoduodenectomy (PD)] in patients with chronic pancreatitis. Background:Chronic pancreatitis is a common inflammatory disease with a prevalence of 10 to 30 cases per 100,000 inhabitants. It is characterized by the progressive conversion of pancreatic parenchyma to fibrous tissue. Different surgical procedures are used in treatment of persistent pain. Methods:Sixty-four patients suffering from chronic pancreatitis with inflammatory mass in the pancreatic head were randomly assigned in 2 treatment groups (PD, n = 32) and (Frey, n = 32). The perioperative course of the randomized controlled trial and the 7 years follow-up have been previously published. All participating patients were contacted with a standardized, validated questionnaire (EORTC QLQ C30) to evaluate the long-term survival, quality-of-life pain, and exocrine and endocrine function. Results:In the 15-year long-term follow-up, the pain control was good and comparable between both groups, but the quality of life was better after Frey procedure in regard of the physical status [PD: 100 (0–100) vs PD: 60 (0–100) (P = 0.011)]. No significant differences in terms of the Pain Score were detected between both groups [PD: 7 (0–100) vs Frey 4 (0–100) P = 0.258]. Seven patients after Frey OP and 6 patients after PD were free of pain. Analyzing the postoperative overall survival, a higher long-term mortality was found after PD (53%) than that found after Frey procedure (30%) resulting in a longer mean survival (14.5 ± 0.8 vs 11.3 ± 0.8 years; P = 0.037). No correlation between endocrine or exocrine pancreatic function and pain was found, whereas continuous alcohol consumption was associated with poorer outcome regarding quality of life (P < 0.001) and pain score (P < 0.001). Conclusions:PD and Frey procedure provide good and permanent pain relief and improvement of the quality of life in long-term follow-up. In addition, a longer survival was found after the organ sparing resection. Together with better short-term results, the organ-sparing procedure seems to be favorable in treatment of chronic pancreatitis.

Genetic variation may influence obesity only under conditions of diet: Analysis of three candidate genes

Under the hypothesis of obesity as a polygenetic disease numerous genes have been associated with an obese phenotype and metabolic co-morbidities. The cannabinoid receptor 1 (CB 1) is part of an underinvestigated system that participates in appetite control. Previous publications suggest that the endocannabinoid systems interact with the better understood leptin-melanocortin axis. Neuropeptide Y (NPY) is a player in the latter. Finally resistin has been shown to influence NPY expression in the brain. In a cohort of 1721 caucasion men and women with a BMI of 25kg/m(2) or more we therefore investigated three candidate polymorphisms at baseline and following 3 months low fat caloric restriction diet by polymerase chain reaction and restriction digestion: the 1359 G/A variant of the cannabinoid receptor 1 (CB1), the L7P variation in neuropeptide Y (NPY) and the -420C>G polymorphism in resistin. Comparing groups according to genotype for each gene separately revealed significant results at baseline only for the CB1 gene. However, upon dieting significant data was found for all 3 genes. Carriers of at least one A allele in CB1 lost more weight and reduced LDL cholesterol more than wildtype patients. LL homocygotes in NPY had a greater reduction in glucose, triglycerides, and LDL cholesterol whereas in resistin carriers of the G allele had a greater reduction in weight and triglycerides. Creating two groups defined by NPY and resistin genotype, respectively, with similar BMI values resulted in significant differences concerning weight loss and metabolic improvement. In conclusion, genetic polymorphisms associated with obesity may become relevant only under the condition of a low calory diet. The presence of a certain genotype may then be beneficial for obesity treatment.

Long-term follow-up in small duct chronic pancreatitis: A plea for extended drainage by "V-shaped excision" of the anterior aspect of the pancreas.

Background:A pancreatic duct diameter (PDD) ranging from 4 to 5 mm is regarded as “normal.” The “large duct” form of chronic pancreatitis (CP) with a PDD >7 mm is considered a classic indication for drainage procedures. In contrast, in patients with so-called “small duct chronic pancreatitis” (SDP) with a PDD <3 mm extended resectional procedures and even, in terms of an “ultima ratio,” total pancreatectomy are suggested. Methods:Between 1992 and 2004, a total of 644 patients were operated on for CP. Forty-one prospectively evaluated patients with SDP underwent a new surgical technique aiming at drainage of the entire major PD (longitudinal “V-shaped excision” of the anterior aspect of the pancreas). Preoperative workup for imaging ductal anatomy included ERCP/MRCP, visualizing the PD throughout the entire gland. The interval between symptoms and therapeutic intervention varied from 12 to 120 months. Median follow-up was 83 months (range, 39–117 months). A pain score as well as a multidimensional psychometric quality-of-life questionnaire was used. Results:Hospital mortality was 0%. The perioperative (30 days) morbidity was 19.6%. Postoperative, radiologic imaging showed an excellent drainage of the entire gland and the PD in all but 1 patient. Global quality-of-life index increased in median by 54% (range, 37.5%–80%). Median pain score decreased by 95%. Twenty-seven patients (73%) had complete pain relief. Sixteen patients (43%) developed diabetes, while the exocrine pancreatic function was well preserved in 29 patients (78%). Conclusion:“V-shaped excision” of the anterior aspect of the pancreas is a secure and effective approach for SDP, achieving significant improvement in quality of life and pain relief, hereby sparing patients from unnecessary, extended resectional procedures. The deterioration of exocrine and endocrine pancreatic functions is comparable with that observed during the natural course of the disease.

Systemic Intravenous Infusion of Bovine Hemoglobin Significantly Reduces Microcirculatory Dysfunction in Experimentally Induced Pancreatitis in the Rat

Objective: To evaluate the effectiveness of bovine hemoglobin on pancreatic microcirculation and outcome in experimental acute rodent pancreatitis. Summary Background Data: Stasis of the pancreatic microcirculation initiates and aggravates acute pancreatitis. Hydroxyethyl-starch (HES) has been shown to improve pancreatic microcirculation. Similarly, bovine hemoglobin might improve rheology due to its colloid effect, but additionally supplies oxygen to oxygen depleted pancreatic tissue. Methods: In Wistar rats, severe acute pancreatitis was induced by administration of glucodeoxycholic acid i.d. and cerulein i.v. Pancreatic microcirculation was continuously monitored by fluorescence microscopy. Fifteen minutes after the initiation of acute pancreatitis, animals received either 0.8 mL bovine hemoglobin (Oxyglobin), HES, or 2.4 mL 0.9% NaCl i.v. at random. After 6 hours, animals were killed and histopathological damage of the pancreas was assessed using a validated histology score (0–16). Results: In comparison to controls, pancreatic microcirculation improved significantly in the HBOC group (mean difference of capillary density 31.4%; standard error 5.6%; P < 0.001; 95% confidence interval for difference 17.5–45.3). HES was not as effective as HBOC substitution. The histology score revealed less tissue damage in the HBOC group [6.25 vs. 9.25 (3–8.5 vs. 8–10.75, P < 0.001)] in comparison to controls and also in comparison to the HES group [6.25 vs. 8 (3–8.5 vs. 6.5–10.25, P < 0.006)]. Conclusions: In severe acute pancreatitis, single i.v. injection of bovine hemoglobin improves pancreatic microcirculation and reduces tissue damage.

Microcirculatory function and tissue damage is improved after therapeutic injection of bovine hemoglobin in severe acute rodent pancreatitis.

Objectives: Stasis of the pancreatic microcirculation initiates and aggravates acute pancreatitis. Bovine hemoglobin has been shown to improve microcirculation in acute pancreatitis if prophylactically infused 15 minutes after initiation of acute pancreatitis. The purpose of this study was to evaluate the therapeutic effectiveness of bovine hemoglobin on pancreatic microcirculation and tissue damage later in the course of experimental acute rodent pancreatitis. Methods: In Wistar rats, severe acute pancreatitis was induced by administration of glyco-deoxycholic-acid intraductally and cerulein intravenously. Pancreatic microcirculation was continuously monitored by intravital microscopy. Three hours after the initiation of acute pancreatitis, animals received either 0.8 mL bovine hemoglobin (Oxyglobin), hydroxyethyl starch (HES), or 2.4 mL 0.9% NaCl intravenously at random. After 6 hours, animals were killed, and histopathological damage of the pancreas was assessed using a validated histology score. Results: Pancreatic microcirculation assessed by leukocyte adherence was significantly improved by the administration of bovine hemoglobin in comparison with normal saline over time (mean difference, 51.6 ± 9.2; P < 0.001) and HES (mean difference, 24.1 ± 9.2; P = 0.037). This result was paralleled by decreased tissue damage in the bovine hemoglobin group as opposed to NaCl (6.75 vs. 12; range, 5.25-7.75 vs. 8.25-14; P < 0.001) and HES (6.75 vs. 9; range, 5.25-7.75 vs. 7.5-10.75; P < 0.001). Conclusion: Therapeutic intravenous infusion of bovine hemoglobin improves pancreatic microcirculation and reduces pancreatic tissue damage in severe acute rodent pancreatitis but is not as effective as early (prophylactic) administration.

Improvement of Impaired Microcirculation and Tissue Oxygenation by Hemodilution with Hydroxyethyl Starch plus Cell-Free Hemoglobin in Acute Porcine Pancreatitis

Aims: To avoid the progression from mild edematous acute pancreatitis (AP) to the severe necrotizing form, one therapeutic option is to improve pancreatic microcirculation and tissue oxygenation. The aim of the study was to evaluate the influence of improved rheology (isovolemic hemodilution) plus enhanced oxygen supply (bovine hemoglobin HBOC-301) on pancreatic microcirculation, tissue oxygenation and survival in severe acute experimental pancreatitis. Methods: Severe AP was induced in 39 pigs (25–30 kg BW) by stimulation with intravenous administration of cerulein plus a pressure- and volume-controlled 10-min intraductal infusion of glycodeoxycholic acid. Seventy-five minutes after induction of AP, animals were randomized and hemodiluted isovolemically (PAOP constant) with either 10% hydroxyethyl starch (HES) 200,000/0.5 plus HBOC-301 (+0.6 g/dl plasmatic hemoglobin; Oxyglobin®, Biopure, Cambridge, Mass., USA), or 10% HES 200,000/0.5, or Ringer’s solution to a hematocrit of 15%. Hemodynamics, oxygen transport parameters, pancreatic microcirculation and tissue oxygen tension were evaluated over 6 h. Then the abdomen was closed, animals were extubated and observed for 6 days. After that, the surviving animals were sacrificed and specimens were taken from the pancreas. The histopathologic findings were scored by two blinded pathologists who quantified acinar necrosis, fat necrosis, inflammation and edema. Results: Isovolemic hemodilution with HES plus HBOC-301 reduced mortality and preserved pancreatic microcirculation compared with Ringer’s solution, but was not significantly different from hemodilution with HES alone. Only treatment with HES plus HBOC-301 normalized pancreatic tissue oxygen tension compared with IHD with HES or Ringer’s solution alone. Conclusions: IHD with HES plus HBOC-301 as a combination of rheologic and O2-delivering therapy may represent a novel therapeutic option for treatment of AP.

Surgical treatment in chronic pancreatitis timing and type of procedure

Pain relief and improvement in the quality of life are of paramount importance for any intervention in chronic pancreatitis. In several trial good results have been published after different drainage procedures and resections. An optimal surgical intervention should manage mainly the intractable pain, resolve the complications of the adjacent organs and achieve the drainage of the main pancreatic duct. An optimal procedure should guarantee a low relapse rate, preserve a maximum of endocrine and exocrine function, and most importantly, restore quality of life. Thus an ideal operation should representing a one-stop-shopping. According to the trials conducted so far, Duodenum-preserving resection of the pancreatic head offers the best short-term outcome. It combines the highest safety of all surgical procedures with the highest efficacy. By varying the extent of the cephalic resection, it offers the possibility of customizing surgery according to the individual patients morphology.