Alvin M. Zfass

Inhibitory beta adrenergic receptors in the human distal esophagus

Intraesophageal manometry was performed on 14 healthy male volunteers divided into two groups. Group 1, composed of 4 subjects, received first phenylephrine (an alpha adrenergic stimulating drug) and then phentolamine (an alpha adrenergic blocking drug) intravenously. No effect on esophageal motility was observed following administration of either drug; however, adequate alpha stimulation or blockade of esophageal adrenergic receptors was probably not accomplished. Group 2 was composed of 10 subjects who received first isoproterenol (a beta stimulating drug) and then alprenolol (a beta blocking drug) intravenously. A significant decrease in resting pressure of the lower esophageal sphincter (LES) was observed in all of 9 subjects following isoproterenol. No effect was observed in the body of the esophagus. Following beta blockade with alprenolol, changes were observed in the body of the esophagus and in the LES. In the body of the esophagus, a rise in amplitude of contraction occurred in 9 of 10 subjects and prolongation of contraction was noted in 7 of 10 subjects. Changes in the LES were the most striking. Increase in amplitude of sphincteric contraction following deglutition was seen in 9 of 10 subjects. Prolongation of sphincteric contractions was most dramatic and was recognized in all 10 subjects. These data suggest an inhibitory beta receptor in the human distal esophagus. Stimulation of these receptors results in decreased LES resting pressure, while blockade of the receptors produces an increase in smooth muscle contraction—probably by removing inhibitory control.

Use of probe-based confocal laser endomicroscopy (pCLE) in gastrointestinal applications. A consensus report based on clinical evidence

Background Probe-based confocal laser endomicroscopy (pCLE) provides microscopic imaging during an endoscopic procedure. Its introduction as a standard modality in gastroenterology has brought significant progress in management strategies, affecting many aspects of clinical care and requiring standardisation of practice and training. Objective This study aimed to provide guidance on the standardisation of its practice and training in Barrett’s oesophagus, biliary strictures, colorectal lesions and inflammatory bowel diseases. Methods Initial statements were developed by five group leaders, based on the available clinical evidence. These statements were then voted and edited by the 26 participants, using a modified Delphi approach. After two rounds of votes, statements were validated if the threshold of agreement was higher than 75%. Results Twenty-six experts participated and, among a total of 77 statements, 61 were adopted (79%) and 16 were rejected (21%). The adoption of each statement was justified by the grade of evidence. Conclusion pCLE should be used to enhance the diagnostic arsenal in the evaluation of these indications, by providing microscopic information which improves the diagnostic performance of the physician. In order actually to implement this technology in the clinical routine, and to ensure good practice, standardised initial and continuing institutional training programmes should be established.

Physiological evaluation of the severity of pancreatic exocrine dysfunction during endoscopy.

Objectives: Despite the advances in pancreatic imaging, there continues to be a need to measure exocrine function to determine which patient requires enzyme supplementation. To evaluate the potential use of a rapid endoscopic test that can be conducted by nonacademic centers, we investigated whether concentration of trypsin in food-stimulated secretion is related to trypsin synthesis and secretion. Methods: Subjects include 22 chronic pancreatitis patients (10 mild, 5 moderate, and 7 severe radiological disease) and 11 healthy controls. During upper gastrointestinal endoscopy, pancreatic secretion was stimulated by a single 30-mL duodenal injection of an enteral diet, followed 5 minutes later by periampullary juice aspiration (endoscopic pancreatic function test [ePFT]). This was followed by a conventional 2-hour marker-perfusion diet-stimulated pancreatic trypsin secretion and synthesis study (2-hour PFT [2hPFT]). Results: Severity of radiological disease was associated with a progressive loss of enzyme secretion measured by the 2hPFT. The endoscopic PFT correlated positively with 2hPFT (r2 = 0.48; P < 0.0001) and an activity of less than 5% of the average normal had a 96% specificity and 75% sensitivity for the detection of pancreatic insufficiency as defined by a loss of greater than 90% of pancreatic secretion. Conclusions: The diagnostic power of endoscopy may be enhanced by the collection of a pancreatic juice sample after enteral feed stimulation because measurement of the trypsin content will identify chronic pancreatitis patients who will be benefited by enzyme supplementation.

Effect of vascular occlusion on small-bowel intraluminal pressures in dogs

Summary1. Intraluminal pressure recordings were obtained in 14 mongrel dogs after either superior mesenteric arterial occlusion (in 7 animals) or superior mesenteric venous occlusion (in 7 other animals).2. Striking elevation of intraluminal pressure was observed after occlusion in 6 of 7 animals in the arterial group and 6 of 7 animals in the venous group.3. After occlusion, the observed pressure changes were recorded earlier in the venous group than in the arterial group.4. Periodic rhythms of intraluminal pressure waves, slower than normal, were noted in several animals.5. The factor(s) which mediate the changes in intraluminal pressure after occlusion are unknown.

Presence of SPINK-1 variant alters the course of chronic pancreatitis

Background and Aims:  There is growing evidence that genetic mutations/variants increase susceptibility to the development and progression of chronic pancreatitis (CP). Several mutations have been identified that have a direct and indirect role in events leading to CP. Mutations in the serine protease inhibitor, Kazal type‐1 (SPINK‐1) gene have been reported to lower the threshold for pancreatitis in the presence of other genetic or environmental factors. The prevalence and impact of SPINK‐1 mutations on the clinical course and outcomes of CP remains unclear. This study was conducted to assess the prevalence of the SPINK‐1/N34S variant in patients with CP, and to understand the impact of the SPINK‐1 mutation on the natural history of CP.

Accuracy of probe-based confocal laser endomicroscopy (pCLE) compared to random biopsies during endoscopic surveillance of Barrett’s esophagus

Background  For surveillance of Barrett’s esophagus (BE), the current standard of random 4-quadrant biopsies misses 10 – 50 % of esophageal neoplasms, and does not permit real-time decision-making. Probe-based confocal laser endomicroscopy (pCLE) permits real-time in vivo histologic assessment of esophageal mucosa during upper endoscopy. Prospective studies comparing the accuracy of pCLE to 4-quadrant biopsies in routine clinical practice are lacking. Methods  Consecutive patients with BE underwent high definition white light and narrow-band imaging followed by pCLE and targeted biopsy or mucosal resection. Four-quadrant biopsies were obtained during the same session. Baseline variables, real-time pCLE interpretation, and histology results were prospectively recorded. Blinded expert review of pCLE sequences and histology specimens was performed. A sample size of 64 patients was calculated a priori based on 3 % estimated prevalence of high grade dysplasia (HGD) or cancer. Results  In total, 66 patients were included in the study. The prevalence of HGD or cancer was 4.55 %. Both real-time and blinded pCLE correctly identified all cases of cancer. For the primary outcome, real-time pCLE was 98 % specific but only 67 % sensitive for HGD/cancer compared to non-blinded pathologist interpretation. For HGD and cancer, inter-observer agreement was substantial between real-time and blinded endomicroscopists (kappa = 0.6). pCLE identified dysplasia in 75 % of cases where both blinded and unblinded pathology interpretation was low grade dysplasia. Conclusions  pCLE demonstrates high specificity for detecting dysplasia and cancer, but lower sensitivity may limit its utility in routine BE surveillance. pCLE may have a role in confirming LGD in real-time before eradication therapy.

The impact of an educational workshop on colorectal screening practices

Since its establishment in 1983, the Virginia Colorectal Cancer Control Project has emphasized the importance of routine screening of asymptomatic adults for colorectal cancer. This has been accomplished through educational workshops that are offered to primary care physicians. These workshops provide didactic information on current concepts in screening and individualized instruction on the use of the flexible sigmoidoscope. Eleven workshops have been conducted since the fall of 1984. During the spring of 1986, a survey was mailed to workshop participants to determine whether changes had occurred in their screening practices. A total of 115 physicians responded to the survey. Prior to the workshop, 86 physicians performed the digital rectal examination; now 100 do. Prior to the workshop, 68 physicians performed the fecal occult blood test; now 89 do. Prior to the workshop, 34 physicians used a flexible scope; now 71 do. Participants found the workshop to be extremely effective in providing individualized instruction.