Pietro Velio

Clinical and morphofunctional features of idiopathic myenteric ganglionitis underlying severe intestinal motor dysfunction: a study of three cases

Ganglionitis, i.e., the inflammatory neuropathy characterized by a marked lymphoplasmacellular infiltrate in the myenteric plexus, may underlie a variety of paraneoplastic, infectious, or neurological disorders, although occasional cases are idiopathic in origin. We report clinical, manometric, morphofunctional, and immunological features of three cases of idiopathic ganglionitis. All patients had megacolon and underwent surgery for repeated episodes of intestinal subocclusion. Esophageal, GI, and colonic manometry performed in one patient showed dysmotility of the whole gut. Histological examination of colonic and ileum specimens identified a prominent lymphoplasmacellular infiltrate within the myenteric plexus along with a marked decrease of a wide array of neuronal peptides/transmitters. In one patient, tissue analysis revealed progressive neuronal changes up to marked myenteric neuron damage. The inflammatory infiltrate in all patients comprised CD4+ and CD8+ T lymphocytes. Abundance of both subclasses of lymphocytes suggests that immune-mediated mechanisms were responsible for neuronal degeneration. In one patient, systemic steroid therapy brought a significant clinical improvement. The immunosuppressive approach deserves further investigation in patients with severe gut motor abnormalities attributable to idiopathic myenteric ganglionitis.

Gastric and duodenal polyps in familial polyposis coli.

Endoscopy with multiple biopsies of the upper gastrointestinal tract was repeated yearly over a two to six year period in nine patients with familial polyposis coli from three families. Adenomatous polyps, one to 20 in number and 2-8 mm in size, were detected in the antrum and the first and second duodenal portions in seven patients, while hyperplastic polyps were detected in four patients in the gastric body. In two patients adenomatous tubules were observed in the biopsies of endoscopically normal mucosa from the same area where adenomatous polyps later developed. Lymphoid polyps were detected in the antrum in three cases. Double contrast radiology correlated poorly with endoscopy in the gastric body; it allowed detection of polyps in the third duodenal portion in two more patients. These results confirm that the incidence of adenomas in the upper gastrointestinal tract in familial polyposis coli may be higher than previously suspected.

Chronic Idiopathic Constipation: Pathophysiology and Treatment

Chronic constipation is common in the general population, especially in women, in its idiopathic form. However, confusion still surrounds its definition, despite recent efforts to standardize it. Constipation can be divided in two large subgroups-normal transit and slow transit. The have different pathophysiological bases still not completely understood. Most patients respond to simple therapeutic measures aimed at correcting dietary fiber intake and lifestyle. Others, however, need more aggressive treatment, including laxatives, psychological therapy, and biofeedback. In a few patients with intractable constipation, surgery might be indicated to give relief.

Lactose malabsorption and intolerance in Italians: clinical implications

Lactose malabsorption was assessed by the hydrogen breath test in 40 Italian patients with irritable bowel syndrome and 42 controls without abdominal disturbances. Sixty-five percent of patients were “low milk consumers” (0–250 ml milk per day) compared with 38% of controls (P<0.02). Lactose loads of 25 and 50 g caused malabsorption in 82.5 and 87.5% patients and in 55 and 62% controls, respectively (patients vs controlsP<0.02). Malabsorption was more frequent in the “low milk consumers” group (P<0.05). During a four-month lactose-free diet as the only treatment 7.5% of patients became symptomfree (and remained so for a further eight-month diet), 52.5% improved, and 40% showed no change.

Respiratory excretion of hydrogen and methane in Italian subjects after ingestion of lactose and milk

Abstract. Lactose malabsorption, by the breath hydrogen test, and lactose intolerance (presence of symptoms) were studied in twenty healthy Italian subjects after intake of 12.5, 25 and 50 g lactose, whole milk and low‐lactose milk. A rise in respiratory concentration of hydrogen (>20 ppm) (malabsorption) was found in fifteen subjects after 50 g lactose, in thirteen after 25 g and in seven after 12.5 g. Symptoms generally occurred in subjects presenting a rise in respiratory hydrogen excretion, but such a rise was often observed without symptoms. Thirteen subjects presented symptoms after 50 g lactose, but only three after 25 g and one after 12.5 g. Whole milk (500 ml) gave a lower incidence of lactose malabsorption than 25 g lactose (7/20 versus 13/20, P < 0.05) and more subjects developed symptoms (7/20 versus 3/20, NS). Low‐lactose milk produced no malabsorbers and one intolerant. Breath methane was detected constantly in seven subjects and in three on some of the days of observation. Respiratory methane excretion generally appeared to be unrelated to lactose ingestion.

Oesophageal manometry in the evaluation of megacolon with onset in adult life.

BACKGROUND: Oesophageal motility is often impaired in patients with megaduodenum and other forms of intestinal pseudo-obstruction in which a visceral myopathy or neuropathy may be present. Idiopathic longstanding megacolon with onset in adult life is still a poorly defined entity, which may also be part of a more widespread motility disorder but in which oesophageal motility has not been yet systematically studied. AIMS: To assess oesophageal motility in patients with longstanding idiopathic megacolon with onset in adult life. PATIENTS: 14 consecutive subjects with idiopathic megacolon whose symptoms began after the age of 10 and a clinical history of 2-22 years. METHODS: Standard barium enema, water perfused oesophageal manometry, and also anorectal manometry. RESULTS: Oesophageal motility was impaired in five patients (36%; 95% confidence intervals 16 to 61%). Normal peristalsis was substituted by low amplitude multiple peaked simultaneous contractions in four subjects and by undetectable contractions in one. In three of them the lower oesophageal sphincter did not relax after swallows; in the same patients anal relaxation after rectal distension was also undetectable. All five patients with impaired oesophageal motility had a colonic dilatation sparing the rectum. Three of them reported constipation and a history of pesudo-obstruction and the other two only abdominal distension. CONCLUSIONS: Oesophageal manometry should be performed in patients with longstanding idiopathic megacolon with onset in adult life, in particular if the rectum is not dilated and even in absence of pseudo-obstruction. This simple test may disclose a more widespread visceral neuropathy or myopathy. Such a diagnosis helps to better understand the cause of the colonic dilatation and may be clinically relevant for treatment of the patients.

Silent Celiac Disease Is Frequent in the Siblings of Newly Diagnosed Celiac Patients

Background/Aims: Celiac disease is caused by environmental and genetic factors, and the relatives of celiac patients are at higher risk of developing celiac disease than the general population. This prospective study evaluates the prevalence of celiac disease in the asymptomatic siblings of celiac patients. Methods: Forty-eight siblings (22 males; mean age 13 years) of 39 celiac children (20 males; mean age 4 years), and 120 siblings (55 males; mean age 33 years) of 55 adult celiac patients (12 males; mean age 31 years) were serologically screened for celiac disease. Positive cases were considered for endoscopic duodenal biopsies. Results: Forty of the 168 asymptomatic siblings (23.8%) were affected by celiac disease. There were no differences between the index cases with and without affected siblings in terms of age at diagnosis, symptoms at onset, order of birth, associated disorders or other affected relatives. The male siblings of pediatric patients were affected in 40.9% of cases and female siblings in 26.9%; the corresponding figures for adults were 16.4 and 23.1%. Conclusions: Silent celiac disease is 24–48 times more frequent in the siblings of celiac patients than in the general population. No predictive factors for sibling involvement were found. Adult females seem to tolerate gluten less than adult males.

Cerebellar degeneration and hearing loss in a patient with idiopathic myenteric ganglionitis

A 35-year-old male with an 11-year history of intestinal pseudo-obstruction associated with an idiopathic inflammatory insult of the myenteric plexus and the presence of circulating anti-Hu antibodies developed a neurological syndrome characterized by bilateral hearing loss, deteriorating balance, an unsteady gait and difficulty in estimating distances. A similar neurological syndrome has previously been described in older patients among the paraneoplasic syndromes associated with small-cell lung carcinoma and the presence of circulating anti-Hu antibodies, but never in the rare cancer-free patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction. The patient underwent a steroid treatment. No further episodes of functional intestinal obstruction were observed and, after an initial improvement, the neurological symptoms stabilized, leaving a permanent reduction in hearing function and an unsteady gait. The case shows that an idiopathic inflammatory insult of the myenteric plexus may precede (and perhaps lead to) central nervous system impairment in patients with anti-Hu-associated chronic idiopathic intestinal pseudo-obstruction.

Postprandial gut peptide plasma levels in women with idiopathic slow-transit constipation.

BACKGROUND As abnormalities of circulating gut regulatory peptides may have pathogenetic relevance in chronic idiopathic slow-transit constipation, we measured fasting and postprandial levels of plasma pancreatic polypeptide, motilin, cholecystokinin, neurotensin, and somatostatin in women with the disease. Results were compared with those of women with normal bowel habits. METHODS Eight women with slow-transit constipation and 10 healthy women were studied. Blood samples were taken at regular intervals in fasting conditions and for 3 h after a standard solid-liquid meal (550 kcal). Gut peptide plasma levels were measured with a radioimmunoassay. RESULTS Fasting gut peptide levels and postprandial pancreatic polypeptide responses were normal in constipated patients, in whom, however, motilin levels did not increase after the meal, and postprandial concentration-time curves of cholecystokinin, neurotensin, and somatostatin were delayed. Mean +/- standard error of the mean peak times in patients and in controls were, respectively, 99 +/- 14.7 and 46 +/- 4.1 min (P < 0.01, Mann-Whitney test) for cholecystokinin, 135 +/- 9.8 and 60 +/- 3.9 min (P < 0.01) for neurotensin, and 111 +/- 17.7 and 51 +/- 6.0 min (P < 0.05) for somatostatin. CONCLUSIONS Patients with slow-transit constipation have abnormal postprandial patterns of motilin, cholecystokinin, neurotensin, and somatostatin.

Small bowel transplantation under oral immunosuppression: experimental study in the pig.

Abstract Despite recent improvements, clinical intestinal transplantation remains an experimental procedure for the treatment of irreversible failure of the intestine. Depending on the extent of additional failures, the transplant of the bowel can also be performed as a part of a multivisceral graft. Although these procedures have been performed preclinically for many years and have also been reported to have a successful outcome in the clinical setting, they have not yet become routine, unlike the transplant of other organs. With the aim of improving clinical results, many groups are studying on experimental models. Experimental studies are predominantly performed in rats, with fewer studies conducted in large animals. In 1992, the authors began an experimental program of orthotopic liver-small bowel transplantation (OLSBTx) and surgical technique. Results in the pig have been described for the first time by our group. Despite an acceptable control of rejection, results of intestinal function were poor. The OLSBTx is a high-risk procedure, and in animals an aggressive postoperative treatment is impossible. We therefore decided to continue with the transplant of the small bowel alone (SBTx) because it is a less demanding procedure.