Achalasia.

Achalasia is a rare motor disorder of the esophagus, characterized by the absence of peristalsis and impaired swallow-induced relaxation. These motor abnormalities result in stasis of ingested food in the esophagus, leading to clinical symptoms, such as dysphagia, regurgitation of food, retrosternal pain and weight loss. Etiology is unknown. Some familial cases have been reported, but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant etiologic factor. Association of achalasia with viral infections and auto-antibodies against myenteric plexus has been reported, but the causal relationship remains unclear. In terms of diagnosis, esophageal manometry is the gold standard to diagnose achalasia. Still, its role in post-treatment surveillance remains controversial. Radiological studies support the initial diagnosis of achalasia and have been proposed for detecting preclinical symptomatic recurrence. Although endoscopy is considered to have a poor sensitivity and specificity in the diagnosis of achalasia, it has an important role in ruling out secondary causes of achalasia. Treatment is strictly palliative. Current medical and surgical therapeutic options (pneumatic dilation, surgical myotomy, and pharmacologic agents) aimed at reducing the lower esophageal sphincter (LES) pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids.

The diagnosis of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is known to cause erosive esophagitis, Barrett esophagus and has been linked to the development of adenocarcinoma of the esophagus. Currently, endoscopy is the main clinical tool for visualizing esophageal lesions, but the majority of GERD patients do not have endoscopic visible lesions and other methods are required. Ambulatory esophageal pH monitoring is the gold standard in diagnosing GERD, since it measures distal esophageal acid exposure and demonstrates the relationship between symptoms and acid reflux. The effectiveness of selective gastric acid suppressive therapy led to the introduction of short trials of proton pump inhibitors (PPIs) to diagnose GERD and they are often used as a first line diagnostic tool in clinical practice and, in particular, in the primary care setting, the current trend being that gastroenterologists are asked to evaluate mainly patients with persistent GERD symptoms while on PPI therapy. In these patients the question is whether the persistent symptoms are or not associated with reflux (acid or nonacid). Recently, either combined multichannel intraluminal impedance and pH monitoring or bilimetry allow to study the mechanisms underlying the persistent symptoms on acid suppressive therapy. Manometry is mandatory prior to any surgical approach and to verify motility disorders that could be associated to GERD.

Treatment with botulinum toxin of octo-nonagerians with oesophageal achalasia: a two-year follow-up study.

BACKGROUND: Treatment of oesophageal achalasia with intrasphincteric injections of botulinum toxin has proved to be a successful alternative treatment modality. However, little is known about its long-term effects in very old patients. AIM: To evaluate the effects of such treatment in octo-nonagerians during a 2-year follow-up period. PATIENTS AND METHODS: Thirty-three patients with idiopathic oesophageal achalasia (range 81-94 years) entered the study. After basal evaluation and screening procedures, 100 U of botulinum toxin was injected at the lower oesophageal sphincter, and the procedure was repeated 1 month later. Data were collected at baseline and were compared after 1 and 2 years following the procedure. RESULTS: Seventy-eight per cent of patients were considered responders at 1 year and 54% were considered responders at 2 years. The weight gain at the end of the follow-up period was 2 (0-3) kg. No significant relationship was found between baseline lower oesophageal sphincter pressure and symptoms score after 1 and 2 years of follow-up; moreover, no major complications of botulinum toxin therapy were reported. CONCLUSION: Treatment of very old achalasic patients with botulinum toxin is safe, effective and yields good quality of life in a substantial proportion of these subjects.

Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease.

BACKGROUND: Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis. AIMS: To investigate the interstitial cells of Cajal (the gut pacemaker cells), together with myenteric and submucosal ganglion and glial cells, in patients with diverticulosis. PATIENTS: Full thickness colonic samples were obtained from 39 patients undergoing surgery for diverticulosis. Specimens from tumour free areas of the colon in 10 age matched subjects undergoing surgery for colorectal cancer served as controls. METHODS: Interstitial cells of Cajal were assessed using anti-Kit antibodies; submucosal and myenteric plexus neurones and glial cells were assessed by means of anti-PGP 9.5 and anti-S-100 monoclonal antibodies, respectively. RESULTS: Patients with diverticulosis had normal numbers of myenteric and submucosal plexus neurones compared with controls (p = 0.103 and p = 0.516, respectively). All subtypes of interstitial cells of Cajal were significantly (p = 0.0003) reduced compared with controls, as were glial cells (p = 0.0041). CONCLUSIONS: Interstitial cells of Cajal and glial cells are decreased in colonic diverticular disease, whereas enteric neurones appear to be normally represented. This finding might explain some of the large bowel motor abnormalities reported to occur in this condition.

Production and pro-apoptotic activity of soluble CD95 ligand in pancreatic carcinoma.

We report here that the progression of pancreatic carcinomas in tumor patients is associated with increased serum levels of both the soluble forms of CD95 ligand (CD95L/FasL) and its receptor, CD95 (Fas). Shedding of proteolytically processed soluble CD95L was also observed in pancreatic carcinoma cells in vitro, thus identifying one possible source of CD95L in patients' sera. Because the secreted forms of both CD95 and CD95L have been implicated previously in protection of cells from CD95-mediated cell death, we assessed the effect of soluble CD95L in supernatants of pancreatic carcinoma cells on viability of Jurkat T lymphocytes. We describe that (a) supernatants derived from cultured pancreatic carcinoma cells caused apoptosis of Jurkat cells; (b) soluble tumor-derived CD95L contributed significantly to this effect; and (c) in comparison to Jurkat cells, pancreatic carcinoma cells themselves revealed increased resistance to apoptosis induction by autocrine soluble CD95L. These results are consistent with the notion that in the microenvironment of pancreatic tumors, tumor-derived shed CD95L exerts paracrine pro-apoptotic effects. In addition, because it is released at high levels into the bloodstream, soluble CD95L may have systemic effects in tumor patients that reach beyond the microenvironment of the tumor site.

Delivery of radiofrequency energy to the gastroesophageal junction (Stretta procedure) for the treatment of gastroesophageal reflux disease.

BACKGROUND: Radiofrequency (RF) energy treatment is increasingly offered before invasive surgical procedures for selected patients with gastroesophageal reflux disease (GERD). METHODS: Thirty-two patients undergoing the Stretta procedure were prospectively evaluated with upper endoscopy, manometry, 24-hour pH testing, SF-36 surveys, and GERD-specific questionnaires (GERD HRQL). RESULTS: Significant clinical improvement was observed in 91% of patients (29/32). Mean heartburn and GERD HRQL scores decreased (p = 0.001 and p = 0.003, respectively), and physical SF-36 increased (p = 0.05). At a minimum follow-up of 12 months, median esophageal acid exposure decreased (p = 0.79) and was normalized in eight patients. Median lower esophageal sphincter (LES) pressure was unchanged. Esophagitis healed in six of eight patients, but two patients with nonerosive disease developed asymptomatic grade A esophagitis during follow-up. At 12 months, 56% of patients were off proton pump inhibits. Morbidity was minimal. CONCLUSIONS: RF delivery to LES is safe and significantly improves symptoms and quality of life in selected GERD patients.

Role of platelet activating factor in acute pancreatitis induced by lipopolysaccharides in rabbits.

In the present study we demonstrated that a single injection of endotoxin (lipopolysaccharides, E. Coli 0111-B4) into the superior pancreaticoduodenal artery of rabbits induced a dose-dependent acute necrotizing pancreatitis. The lesions observed by light microscopy were significant for 10 micrograms lipopolysaccharides and were maximal for 20 micrograms. After 24 h the main findings were edema, acinar cell vacuolisation, polymorphonuclear neutrophil infiltration and tissue necrosis. The pancreatic lesions developed strictly in the area supplied by the artery injected with lipopolysaccharides, without significant intestinal involvement. Since platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3- phosphocholine, PAF; 50-500 ng), a phospholipid mediator of endotoxin-induced inflammation and shock, was previously shown to cause an acute necrotizing pancreatitis in rabbits, the role of PAF in the development of acute pancreatitis induced by lipopolysaccharides was studied by evaluating: (1) the synergism between doses of lipopolysaccharides (5-10 micrograms), which produced a mild tissue injury, and doses of PAF (10 ng) not producing, per se, any significant injury, and (2) the effect of three structurally unrelated PAF receptor antagonists. The results obtained demonstrated that 10 ng of PAF significantly potentiated pancreatic tissue damage induced by 10 micrograms of lipopolysaccharides.(ABSTRACT TRUNCATED AT 250 WORDS)

Are colonic regular contractile frequency patterns in slow transit constipation a relevant pathophysiological phenomenon?

BACKGROUND: Pathogenesis of slow transit constipation still remains elusive. Some studies have shown several colonic motor abnormalities; however, it is not easy to understand the relative importance of the single ones. AIMS: Since it has been hypothesized that an excess of periodic distal motor activity may be of pathophysiological importance in patients with slow transit constipation, we evaluated regular colonic contractile frequencies in a homogeneous cohort of these patients. PATIENTS: A total of 26 female patients (age range 34 to 67 years) fulfilling the Rome II criteria for constipation entered the study. No patient had evidence of secondary forms of constipation and distal obstruction. METHODS: Twenty-four hour colonic manometric studies were obtained for each patient. Regular contractile patterns (with frequencies ranging from 2 to 8 cycles/min) were calculated for the entire recording period and in single colonic segments. RESULTS: Overall, regular patterns accounted for about 3% of the total colonic motor activity (average 30 min/day per subject), with the 3 cycles/min being the predominant contractile rhythm. Most of this activity was present in the sigmoid colon, accounting for >50% of the total amount of motility, and it was more prevalent than in the descending and transverse colon; no differences were revealed in the descending with respect to the transverse colon. No daily fluctuations of regular contractile activity, nor a cyclic pattern, nor migration between recording points were observed. CONCLUSIONS: Regular colonic frequency patterns are probably of minor pathophysiological importance in slow transit constipation, even in the light of the scant amount of such phenomena previously documented in healthy subjects.

Endoscopic therapies for the management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common disorder with rising incidence worldwide and very high medical costs to society. The medical management of the disease i.e. lifestyle modifications and proton pump inhibitors reaches excellent results in most cases, but it needs to be continued, lifelong; the real cure of the disease is nowadays laparoscopic fundoplication, which is effective and safe in over 95% of well selected patients to provide a durable high quality of life. A very attractive alternative to these well established therapies is the endoscopic treatment of GERD, that employs different endoluminal technologic skills: plication of gastric cardia folds by suturing devices, radiofrequencies thermal-induced cardial fibrosis and bulking or sclerosing agents local injections have been recently tried and validated by different very experienced endoscopic groups. Although endoscopic therapy of GERD seems to be safe and feasible, a definite judgement awaits the results of multicentric controlled studies and longer periods of follow-up; for the present they must be restricted to well experienced endoscopists working to these controlled trials.

[Esophageal motility disorders]. / Le alterazioni motorie dell'esofago.

Esophageal motility abnormalities are usually diagnosed when esophageal manometry is performed in patients with unexplained non-cardiac chest pain, non obstructive dysphagia or as a part of the preoperative evaluation for surgery of gastroesophageal reflux. Classification of these abnormalities has been a subject of controversy. These esophageal contraction abnormalities can be separated manometrically from the motor pattern seen in normal subjects, however, their clinical relevance is still unclear and debated. Many patients demonstrate motility abnormalities in the manometry laboratories, but may lack correlation with their presenting symptoms. Medical treatment can decrease symptoms particularly chest pain or acid reflux but there is no significant changes in the manometric patterns. Such motor abnormalities may not reflect a true disease state, but they could be markers of other abnormalities and they can modify the initial manometric findings in time.

Acute recurrent diverticulitis is prevented by oral administration of a polybacterial lysate suspension.

AIM: The main cause of acute diverticulitis is the abnormal accumulation of fecal bacteria within the diverticular lumen, leading to a balancing between normal probiotic microflora and pathogenic species; Gram negative Entero-bacteriaceae, mainly Escherichia coli and Proteus spp, are the genders that usually cause the disease-related symptoms, due to their ability to adhere to intestinal mucosa. The intestine is well known as the largest human lymphoepithelial organ and daily produces more antibodies, mainly secretory IgAs, than do all other lymphoid tissues. IgAs have different immune and anti-inflammatory properties. The aim of this study was to verify the efficacy of an oral immunostimulant highly-purified, polymicrobial lysate in the prevention of recurrent attacks of diverticulitis and in the improvement of symptoms. METHODS: The study was carried out on 83 consecutive patients suffering from recurrent symptomatic acute diverticulitis and with at least 2 attacks in the previous year; patients were randomly assigned to receive (group A) an oral polybacterial lysate suspension or to a no-treatment clinical follow-up as controls (group B). RESULTS: A total of 76 patients (41 in group A and 35 in group B) terminated the study period. the sums of the scores for symptoms, reported on day schedules, were calculated and examined by means of ANOVA statistical analysis. Statistical differences between group A vs group B were recorded after 1 month (p<0.05) and 3 months (p<0.01) of treatment with the oral polybacterial lysate suspension. CONCLUSIONS: Our data suggest that the administration of an oral enterovaccine for the prophylaxis of recurrent diverticulitis is effective and well tolerated, probably due to a direct stimulation of IgA-mediated mucosal defences.