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Biomedical subjects

M Fein

Publications and source records attributed to M Fein.

At least 19 recordsLinked to original sources

Laparoscopic fundoplication--short- and long-term outcome.

Gastroesophageal reflux disease is probably the most frequently occurring benign functional disorder in the Western industrial countries. With the increasing popularity of laparoscopic anti-reflux procedures, issues on the appropriate technique have been revitalized. The purpose of this study is to evaluate the short- and long-term outcomes of laparoscopic fundoplication and reflect on the perspective of an increasing frequency of performed operations. The data sampling is based on a literature review and a questionnaire. It can be summarized that reflux recurrence due to breakdown of the wrap or herniation of the wrap can also develop in later years after the primary surgery and amount up to 8%. Persistent dysphagia is a severe problem in the first post-operative year, but usually decreases with time and is limited to rates of 3-5% on the long-term follow-up. Other functional problems, such as gasbloat, meteorism and epigastric pain--the cause often cannot be further detected or specified--limit the quality of life of patients after laparoscopic anti-reflux surgery in the long-term follow-up in up to 5% of cases. Side effects of laparoscopic antireflux procedures can be limited to 5 to 10%, but not totally avoided.

Chronic Disease↗

Evaluation of the intestinal microflora in the rat model for esophageal adenocarcinoma.

Surgically induced duodenal reflux results in cancer development in the rat esophagus. One proposed mechanism of carcinogenesis relies on the production of carcinogens in the presence of bacterial overgrowth. Against this background, intestinal microflora in the rat jejunum was analyzed before and after reflux-inducing surgery. Total gastrectomy and esophagojejunostomy were performed on Sprague-Dawley rats to produce esophageal reflux of duodenal juice (n = 12). Three days before surgery they were randomized into three groups: animals which received tap water; animals which received acidified water at pH 1.8; and animals subjected to oral decontamination with triple antibiotics. During surgery and at autopsy after 2 weeks, intestinal juice was aspirated and analyzed immediately for bacterial content. The physiologic microflora of the rat jejunum contained Lactobacillus spp. and Bacteroides spp., both of which were resistant to the antibiotic regimen. Bacterial overgrowth with fecal bacteria was found following surgery. Acidified water did not alter the intestinal microflora. Triple antibiotics eliminated Escherichia coli and Proteus spp. and reduced the concentration of Enterococcus spp. Bacterial overgrowth by bacteria of the fecal flora occurs in the rat model of esophageal adenocarcinoma with the potential to catalyze the production of carcinogens.

Adenocarcinoma↗

Duodenogastric reflux and foregut carcinogenesis: analysis of duodenal juice in a rodent model of cancer.

The incidence of esophageal adenocarcinoma is increasing rapidly. In rats, surgically induced duodenoesophageal reflux is carcinogenic. One proposed mechanism of carcinogenesis is based on the reaction of physiological bile acids with nitrite to produce carcinogenic N:-nitroso amides. To test this hypothesis, duodenal juice was analyzed for endogenously formed N:-nitroso bile acids and its genotoxicity was determined. Esophagojejunostomy was performed on 15 Sprague-Dawley rats to produce duodeno-esophageal reflux. At the time of surgery and 2 and 6 weeks later, duodenal contents were aspirated and analyzed immediately. High performance liquid chromatography coupled to tandem mass spectrometry was used to detect bile acids and their nitroso derivates. Genotoxicity was assessed using a micronucleus test. The characteristic pattern of bile acid derivatives, with taurocholic acid (TCA) and glycocholic acid (GCA) as the predominant conjugates, was detected in all samples. However, even selective reaction monitoring experiments failed to demonstrate the presence of any N:-nitroso-TCA or N:-nitroso-GCA. In addition, other nitroso derivatives could not be detected in any of the samples by neutral loss experiments monitoring the loss of nitric oxide (detection limit 0.1% of the concentration of TCA). All samples were cytotoxic, but neither the preoperative nor the postoperative samples were genotoxic. Duodenal juice was cytotoxic but not genotoxic. Tumorigenesis of esophageal adenocarcinoma in the rodent model could not be linked to a specific carcinogen, especially not to nitroso bile acids. Chronic inflammation is likely to be the mechanism of carcinogenesis by duodenogastric reflux.

Adenocarcinoma↗

[Epidemiology and pathophysiology of Barrett esophagus].

The pathophysiology of Barrett's esophagus appears to be a sequential process; the squamous epithelium of the esophagus is replaced by multipotent undifferentiated cells; secondary to cellular damage in the course of gastroesophageal reflux disease these undifferentiated cells further differentiate under the ongoing influence of mucosal damage, thus forming the typical morphology of Barrett mucosa. While the prevalence of gastroesophageal reflux disease amounts to 10% to 30%, the prevalence of Barrett's esophagus is estimated to be 1% in the general population. The epidemiologic data of Barrett's esophagus gain special attention with regard to the fact that the specialized columnar epithelium with intestinal metaplasia represents the only recognized risk factor for the development of adenocarcinoma in the esophagus. Currently it is estimated that the risk of the development of an adenocarcinoma on the basis of Barrett's esophagus is about 30-50 fold higher than that in the general population.

Adenocarcinoma↗

Loss of function of Trp53, but not Apc, leads to the development of esophageal adenocarcinoma in mice with jejunoesophageal reflux.

INTRODUCTION: APC and TP53 are tumor suppressor genes known to be altered frequently in human esophageal adenocarcinoma (EAC), which arises as a complication of reflux disease. To determine the functional role of these genes in the development of EAC, we have created reflux in mice gene-targeted for either Trp53 or Apc. METHODS: Wild-type (WT), p53-knockout (Trp53-/-), or Apc-mutated (ApcMin/+) mice were generated in our breeding colony. Total gastrectomy with esophagojejunostomy was performed at 6 weeks of age, creating jejunoesophageal reflux. Unoperated control mice were maintained under identical conditions. Mice were sacrificed at 30 weeks of age. Histology of the esophagus and jejunal anastamosis or gastroesophageal junction was reviewed by a single pathologist blinded to the genotype of the animal. RESULTS: The esophagus was normal in all of the unoperated mice (6 ApcMin/+, 6 WT, and 6 Trp53-/-). All operated mice (6 ApcMin/+, 12 WT, and 4 Trp53-/-) had esophagitis, with squamous hyperplasia and early focal ulceration. Barrett's metaplasia was identified in 33% of the operated ApcMin/+ (2/6) and 25% of the Trp53-/- (1/4) mice, but not in the WT mice. Of 4 operated Trp53-/- mice, all developed severe dysplasia of the squamous epithelium and 2 (50%) had EAC on histology, although no gross tumors were seen. No severe dysplasia or carcinoma was identified in any of the ApcMin/+ or WT mice. CONCLUSIONS: Loss of either Trp53 or Apc leads to the development of columnar metaplasia, whereas loss of Trp53, but not Apc, leads to development of cancer in mice with jejunoesophageal reflux.

Adenocarcinoma↗

Comparison of different J-pouches vs. straight and side-to-end coloanal anastomoses: experimental study in pigs.

PURPOSE: Functional results after low anterior resection with straight coloanal anastomosis are poor. Although certain functional aspects are improved with coloanal J-pouch anastomosis, evacuation difficulties are encountered in some of these patients. The aim of the study was to investigate the functional results of different reconstruction methods after low anterior resection in a standardized pig model. METHODS: Thirty-two adult Göttinger mini pigs were randomly assigned either to straight end-to-end (Group 1), side-to-end (Group 2), small (4-cm limb length) J-pouch (Group 3), or large (8-cm limb length) J-pouch (Group 4) coloanal anastomosis after low rectal excision. The animals were investigated 12 weeks after the operation by measuring neorectal compliance and ceruletide-induced defecation. Eight pigs without operation were used as controls (Group 5). RESULTS: Compliance was lowest in Groups 1 and 2, which were significantly different compared with both pouch designs and controls. Neorectal compliance of pigs with either small or large pouches did not differ significantly compared with one another or controls. Defecation was significantly impaired in pigs with a large pouch compared with all other groups. Pigs with side-to-end anastomoses had as rapid an evacuation as animals with straight coloanal reconstruction. CONCLUSION: Coloanal J-pouch reconstruction adequately restores reservoir capacity after low anterior resection of the rectum. From a functional point of view, side-to-end is not superior to straight coloanal anastomosis. Compared with small pouches, a large pouch design does not lead to better neorectal compliance in the pig model, whereas pouch evacuation seems to be considerably compromised.

Anal Canal↗

Treatment of advanced gastroesophageal reflux disease with Collis gastroplasty and Belsey partial fundoplication.

OBJECTIVE: To examine the factors affecting outcome in patients with advanced gastroesophageal reflux disease. DESIGN: Retrospective analysis. SETTING: University tertiary referral center. PATIENTS: Thirty-seven patients with advanced gastroesophageal reflux disease and no previous antireflux surgery. INTERVENTIONS: Thirty patients underwent Collis gastroplasty for esophageal lengthening and Belsey partial fundoplication. Seven patients with esophageal stricture and global loss of esophageal body motility who underwent primary esophagectomy and reconstruction were used as a comparison group. OUTCOME MEASURES: Symptomatic outcome in all 37 patients was assessed by questionnaire at a median of 25 months (range, 5-156 months) after surgery. In a subset of 11 patients undergoing the Collis-Belsey procedure, outcome was measured using 24-hour pH and results of motility studies. RESULTS: The Collis-Belsey procedure was successful in relieving symptoms of gastroesophageal reflux in 21 (70%) of the 30 patients. The outcome was excellent or good in 16 (89%) of 18 patients who presented with symptoms other than dysphagia, but only in 5 (42%) of 12 patients with dysphagia (P = .01). The outcome was particularly poor if dysphagia was associated with a previously dilated esophageal stricture. Persistent or induced dysphagia was the reason for failure in all but 1 patient. Results of 24-hour esophageal pH studies were returned to normal in 8 (73%) of 11 patients undergoing postoperative evaluation. Contraction amplitudes in the distal esophagus and the prevalence of simultaneous contractions in these segments did not change after the operation. All 7 patients who underwent primary esophagectomy were classified as having an excellent or good outcome and were relieved of their reflux symptoms, including dysphagia. Six of these could eat 3 meals per day and enjoyed an unrestricted diet. CONCLUSIONS: The outcome of the Collis-Belsey procedure in patients with advanced gastroesophageal reflux disease without dysphagia is excellent. It is less so in patients with dysphagia as a preoperative symptom. Esophagectomy can provide a good outcome in patients who have a combination of dysphagia stricture and a profound loss of esophageal motility.

Adult↗

Inter- and intraindividual reproducibility of anorectal manometry.

BACKGROUND: This study investigates the inter- and intraindividual variability of normal values and, thus, the reproducibility of anorectal manometry. MATERIALS AND METHODS: Following a standardized protocol, three anorectal manometries were performed 4 h apart on 2 days of investigation, with an interval of 4 weeks, in ten healthy volunteers. Measured parameters in all 60 manometries were: sphincter length (SL), resting pressure (RP), maximum squeeze pressure (MSP), relaxation of the internal anal sphincter (RIAS), and rectal compliance (RC). Interindividual variability was expressed as standard deviation from calculated mean values and intraindividual variability was tested with Wilcoxon's test for tied samples and Spearman's rank correlation test. RESULTS: A large interindividual variability was found for all measured parameters, except for SL, reflecting the extensive absolute range of measured values. Median intraindividual variability among the six individual measurements and between both measurement days revealed that MSP, RIAS and RC are parameters which were not reproducible in this volunteer study. A significant correlation between the results of the repetitive measurements and, thus, a good reproducibility was only found for the parameters SL and RP. CONCLUSIONS: Anorectal manometry has only limited diagnostic value; although rather exact quantifications of individual parameters can be achieved, the impact of these measurements should be regarded rather critically, since only SL and RP appeared to be reproducible parameters.

Adult↗

Application of the new classification for cancer of the cardia.

BACKGROUND: Cancer of the cardia is now topographically classified into three types: type I, with the tumor center in the distal esophagus treated with subtotal esophagectomy; type II, arising at the gastroesophageal junction and treated with distal esophagectomy and either proximal or total gastrectomy; and type III, subcardial cancer treated with extended total gastrectomy. Our objective was to review the new classifications and compare the outcomes in patients grouped and treated according to these classifications. METHODS: Seventy-four patients with cancer of the cardia--15 with type I, 30 with type II, and 29 with type III cancer--underwent surgical resection at our institution between 1992 and 1997. Postoperative complications, UICC stages, and survival (Kaplan-Meier) were compared. RESULTS: The majority of patients with type I (73%) or type II (53%) cancer had stage I or II tumors, but only 27% of patients with type III cancer had this tumor stage (P < .05). Overall 30-day mortality was 4% and morbidity was 31%. Curative resections were performed in 73% (54 of 74) of the patients with 3-year survival rates of 72% (type I), 68% (type II), and 61% (type III). CONCLUSION: The recommended therapy for the different types of cancer of the cardia results in acceptable morbidity, mortality, and survival rates.

Adenocarcinoma↗

[Laparoscopic anti-reflux surgery--report of experiences from Germany].

This is a report on a questionnaire in Germany reflecting the activity in antireflux surgery, both in open and laparoscopic modifications in the time period of 1990 through 1995. It serves as an overview of the acceptance of diagnostic workup, indication, applied techniques, and different antireflux procedures. In a total of 104 representative hospitals, 2,036 patients were operated during this time. Almost 80% of the hospitals provide antireflux surgery in the open technique and only 1/3 of the hospitals have experience in the laparoscopic technique. There is a total rise in antireflux surgery during the last 5 years, since the number of laparoscopic antireflux operations rises constantly with a total amount of open operations of about 250 cases per year. In open surgery the most favourite technique is the Nissen-Rossetti procedure, while in laparoscopic technique the choice for the original Nissen, the Nissen-Rossetti, or the floppy Nissen technique is divided in almost equal parts.

Cross-Sectional Studies↗

Isolated upright gastroesophageal reflux is not a contraindication for antireflux surgery.

BACKGROUND: Patients with gastroesophageal reflux disease who reflux only in the upright position are thought to have a less severe abnormality. Controversy exists over whether these patients should be considered candidates for antireflux surgery. METHODS: A total of 224 consecutive patients with increased esophageal acid exposure on 24-hour pH monitoring were classified as having upright (n = 54), supine (n = 72), or bipositional (n = 98) reflux and were evaluated by manometry and endoscopy. Of these, 116 patients had a laparoscopic Nissen fundoplication. Their clinical outcome at a median of 12 months (range 4 to 44 months) was compared. RESULTS: Patients with upright reflux had a lower prevalence of a structurally defective lower esophageal sphincter, fewer hiatal hernias, and less esophageal injury when compared to those with bipositional reflux (p < 0.005). Excellent (asymptomatic) or good outcome (minor symptoms not requiring acid suppression therapy) was achieved in 86% of the patients with upright reflux, 90% of those with supine reflux, and 89% of those with bipositional reflux. CONCLUSIONS: Patients with upright reflux have less complicated, earlier disease and have results equivalent to those patients with supine and bipositional reflux after antireflux surgery.

Adolescent↗

Can the combination of symptoms and endoscopy confirm the presence of gastroesophageal reflux disease?

The aim of this study was to evaluate the accuracy of symptomatology and esophagogastroduodenoscopy (EGD) in the diagnosis of proven gastroesophageal reflux disease (GERD). We evaluated the symptoms and EGD findings of 100 consecutive patients presenting with symptoms suggestive of GERD. Patients' symptoms were scored at their first visit with a standardized symptom scoring system (grades 0-3). Grade 3 symptoms were the most severe. EGD findings were classified according to the modified Savary-Miller scale. Esophageal acid exposure was quantified using 24-hour esophageal pH monitoring; a positive composite score was considered evidence of GERD. Fifty-seven patients had positive pH scores, and 43 were negative. The combination of grade 2 or 3 heartburn and/or regurgitation with erosive esophagitis or Barrett's esophagus on EGD had a 97 per cent specificity and 64 per cent sensitivity for accurately diagnosing GERD. It is concluded that, in the presence of moderate to severe symptoms and endoscopic injury, the diagnosis of GERD can be made without further studies. However, 24-hour esophageal pH monitoring is still indicated in patients with mild typical symptoms, atypical symptoms, or when the combination of heartburn and regurgitation, regardless of their severity, occurs in the absence of severe mucosal damage.

Adolescent↗

Fiberoptic technique for 24-hour bile reflux monitoring. Standards and normal values for gastric monitoring.

Physiologic bile reflux was assessed in 27 in vivo test with healthy volunteers to define a standardized protocol and normal values for 24-hour enterogastric bile reflux monitoring (protocol with supine, upright, and meal phases and a free diet avoiding alcohol, smoking, and coffee, evaluation with different thresholds of absorbance units: 0.14, 0.25). In vitro tests with bile-sodium solutions demonstrated a linear dependence of absorbance for bilirubin up to 600 mumol/liter (range of the fiberoptic device: 0.0-1.0). Fluids and food might interfere with absorbances below 0.25 (exception: coffee). In vivo bile often remains in the stomach for more than 1 hr; these events were defined as reflux episodes. The upper limits for physiologic bile reflux are a percentage of total time of bile reflux of 28.2% and an average absorbance during a reflux episode of 0.62 (95th percentile with threshold 0.25). Comparing bile with pH monitoring (absorbance > 0.25 and/or pH > 4), an increase of bilirubin was found most frequently with constant pH (45%) or an increase of pH with constant bilirubin (36%). The hypothesis was drawn that bile and duodenal or pancreatic secretions may separately contribute to duodenogastric reflux.

Adult↗

Quantification of color Doppler for the evaluation of tissue vascularization.

Assessment of tissue vascularization with color Doppler (CD) can improve differential diagnosis of tumors. Until now, measurement of flow velocities is restricted to conventional duplex ultrasound of single vessels or semiquantitative scoring of the vessel distribution in CD. We developed a new method for quantification of CD data in organs or tumors by statistical image analysis. Based on standardized image recording, data is acquired from the video output of any ultrasound scanner using a 24-bit color framegrabber in a personal computer. The digitized colors are recognized according to their position in the CD palette bar resulting in an 8-bit color image (number of identified pixels > 99.9%). Within the region of interest, statistics of the detected flow patterns are calculated. The color pixel density and the mean color value varies between recordings of the same image during subsequent systolic peaks with a SD of 10% and 2%, respectively, and within different sections of the same organ or tumor with 25% and 10-50%. This analysis can be used for comparative or longitudinal studies and an objective evaluation of CD in complex vascular formations such as tumors. Its diagnostic impact has already been demonstrated in clinical studies.

Blood Flow Velocity↗

Current aspects of gastroduodenal ulcer disease: diagnosis of pathophysiologic background and indications for operative therapy.

The management of gastroduodenal ulcer disease has changed because of new evidence of its pathophysiologic background and the introduction of new medication and operative techniques. Proximal gastric vagotomy (PGV) was abandoned by some as the treatment of choice because of high recurrence rates. With the advent of minimally invasive surgery, laparoscopic vagotomy has renewed interest in vagotomy as a treatment option for gastroduodenal ulcer disease. In view of this development, a study was performed to investigate the incidence of abnormal gastric hyperacidity in a population of ulcer patients in order to select those patients for operative acid reduction who will benefit most from operation. Sixty-eight patients with gastroduodenal ulcer disease underwent 24-hour-gastric-pH monitoring, 29 of these patients subsequently underwent proximal gastric vagotomy. The study demonstrates that it is possible to identify patients with hyperacidity. It revealed a variation of intraluminal gastric acidity in patients with different ulcer locations. On the basis of the opinion that gastric hyperacidity is the main indication for PGV, it is emphasized that the choice of surgery should depend on the functional defect and that the indication for operation should be based on therapy-resistant symptoms.

Duodenogastric Reflux↗

Lateral mobility of lipid analogues and GPI-anchored proteins in supported bilayers determined by fluorescent bead tracking.

Lipid analogues and glycosylphosphatidylinositol (GPI)-anchored proteins incorporated in glass-supported phospholipid bilayers (SBL) were coupled to small (30 nm diameter) fluorescent beads whose motion in the liquid phase was tracked by intensified fluorescence video microscopy. Streptavidin (St), covalently attached to the carboxyl modified surface of the polystyrene bead, bound either the biotinylated membrane component, or a biotinylated monoclonal antibody (mAb) directed against a specific membrane constituent. The positions of the beads tethered to randomly diffusing membrane molecules were recorded at 0.2 sec intervals for about 1 min. The mean square displacement (rho) of the beads was found to be a linear function of diffusion time t, and the diffusion coefficient, D, was derived from the relation, rho(t) = 4Dt. The values of D for biotinylated phosphatidylethanolamine (Bi-PE) dispersed in an egg lecithin:cholesterol (80:20%) bilayer obtained by this methodology range from 0.05 to 0.6 micron 2/sec with an average of mean value of D = 0.26 micron 2/sec, similar to the value of mean value of D = 0.24 micron 2/sec for fluorescein-conjugated phosphatidylethanolamine (Fl-PE) linked to St-coupled beads by the anti-fluorescein mAb 4-4-20 or its Fab fragment. These values of D are comparable to those reported for Fl-PE linked to 30 nm gold particles but are several times lower than that of Fl-PE in the same planar bilayer as measured by fluorescence photobleaching recovery, D = 1.3 microns 2/sec. The mobilities of two GPI-anchored proteins in similar SBL were also determined by use of the appropriate biotinylated mAb and were found to be mean value of D = 0.25 and 0.56 micron 2/sec for the decay accelerating factor (DAF, CD55) and the human Fc gamma RIIIB (CD16) receptors, respectively. The methodology described here is suitable for tracking any accessible membrane component.

Animals↗