Ultrasound guided fine needle biopsy of early hepatocellular carcinoma complicating liver cirrhosis: a multicentre study.

BACKGROUND: Because hepatic cirrhosis is a major risk factor for hepatocellular carcinoma, recent guidelines by the European Association for the Study of the Liver (EASL) on clinical management of hepatocellular carcinoma recommend periodic ultrasound surveillance of cirrhotic patients with immediate workup for nodules >1 cm; an increase in the frequency of screening is considered sufficient for smaller lesions. AIMS: To determine the actual risk of hepatocellular carcinoma associated with the latter lesions and to assess the role of ultrasound guided-fine needle biopsy in their diagnosis. PATIENTS AND METHODS: Data were analysed for 294 new nodular lesions <20 mm, including 48 that were <10 mm, detected during a prospective multicentre study involving ultrasound surveillance of 4375 patients with hepatic cirrhosis. In the absence of alpha fetoprotein (AFP) levels diagnostic of hepatocellular carcinoma, ultrasound guided-fine needle biopsy was performed (n = 274). AFP and fine needle biopsy diagnoses of malignancies (hepatocellular carcinoma and lymphoma) were considered definitive. Non-malignant fine needle biopsy diagnoses (dysplastic or regenerative nodule) were verified by a second imaging study. Diagnoses of hepatocellular carcinoma based on this study were considered definitive; non-malignant imaging diagnoses were considered definitive after at least one year of clinical and ultrasound follow up. RESULTS: Overall, 258/294 (87.6%) nodules proved to be hepatocellular carcinoma, including 33/48 (68.7%) of those < or =10 mm. Overall typing accuracy of ultrasound guided-fine needle biopsy was 89.4%, and 88.6% for lesions < or =10 mm. CONCLUSIONS: In a screening population, well over half of very small nodules arising in cirrhotic livers may prove to be hepatocellular carcinoma, and approximately 90% of these malignancies can be reliably identified with ultrasound guided-fine needle biopsy.

Long term efficacy, safety, and tolerabilitity of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation.

AIMS: To assess the long term therapeutic effectiveness, safety, and tolerability of low daily doses of isosmotic PEG electrolyte solutions (PMF-100) administered for a six month period for the treatment of functional constipation, in a double blind, placebo controlled, parallel group study. METHODS: After an initial four week run in period with PMF-100 (250 ml twice daily; PEG 14.6 g twice daily), 70 patients suffering from chronic constipation (58 females, aged 42 (15) years) with normalised bowel frequency (>3 bowel movements (bm)/week) were randomly allocated to receive either PMF-100 or placebo, contained in sachets (one sachet in 250 ml of water twice daily) for 20 weeks. Patients were assessed at four week intervals, and reported frequency and modality of evacuation, laxative use, and relevant symptoms on a diary card. At weeks 1, 12, and 24, a physical examination and laboratory tests were performed. RESULTS: Complete remission of constipation was reported by a significantly (p<0.01) higher number of patients treated with PMF-100 compared with placebo at each four week visit. At the end of the study, 77% of the PMF-100 group and 20% of the placebo group were asymptomatic. Compared with placebo, patients treated with PMF-100 reported hard/pellety stools and straining at defecation less frequently, a significantly higher bowel frequency (week 12: 7. 4 (3.1) v 4.3 (2.5) bm/week, 95% CI 1.64, 4.42; week 24: 7.4 (3.2) v 5.4 (2.1) bm/week, 95% CI 0.13,3.93), reduced consumption of laxative/four weeks (week 12: 0.7 (2.7) v 2.2 (3.3), 95% CI -2.29, 0. 03; week 24: 0.2 (0.8) v 1.4 (2), 95% CI -2.07, -0.023), reduced mean number of sachets used (week 12: 33 (13) v 43 (12), 95% CI -17. 24, 4.56; week 24: 33 (13) v 44 (12), 95% CI -19.68, -2.24), and reduced number of drop outs for therapy failure (16 v 3; p<0.005). Adverse events, physical findings, laboratory values, palatability, and overall tolerance of the solutions did not differ between groups. CONCLUSIONS: Administration of small daily doses of isosmotic PEG electrolyte balanced solutions was effective over a six month period for the treatment of functional constipation. A mean daily dose of approximately 300 ml of PEG solution (PEG 17.52 g) appeared to be safe, well tolerated, and devoid of significant side effects.

Use of polyethylene glycol solution in slow transit constipation.

Patients with long-standing functional slow-transit constipation were treated with low daily doses of polyethylene glycol solutions. Bowel frequency, stool consistency and colonic transit time improved markedly during the treatment. No relevant side-effects were reported during the study period.

Intact colonic motor response to sudden awakening from sleep in patients with chronic idiopathic (slow-transit) constipation.

PURPOSE: There are few data about the relationships between colonic motor behavior and higher brain functions, such as sleep. Previous studies were done in healthy subjects, and it is unknown whether patients with functional motor disorders of the colon behave differently. This study was designed to characterize colonic motor activity in patients with constipation, both during sleep and after sudden awakening, and to compare it with that of healthy subjects. Our working hypothesis was that patients with constipation would have an impaired response to sudden awakening. PATIENTS AND METHODS: Twelve chronically constipated women, 22 to 49 years old, were recruited for the study, and their data were compared with those obtained from 12 healthy female volunteers, 21 to 38 years old. Manometric studies were performed in the descending and sigmoid colon for 30 minutes during sleep (immediately before awakening) and 30 minutes after being awakened suddenly. A motility index was calculated before and after the stimulus. RESULTS: In both groups motility in the descending and the sigmoid colon was almost absent during sleep and significantly increased after sudden awakening. No difference in postawakening values was found between patients with constipation and controls. CONCLUSIONS: In patients with chronic constipation, the brain-gut control of some fundamental mechanisms governing colonic motility is preserved. These data suggest that the alterations of colonic motility described in chronic constipation may be caused by an intrinsic dysfunction of the viscus.

The nutcracker esophagus: a late diagnostic yield notwithstanding chest pain and dysphagia.

The nutcracker esophagus, a primary motor disorder, is frequently associated with noncardiac chest pain. However, there are no data on whether its diagnosis, as in other esophageal motility disorders, is delayed. Since the disorder is frequently heralded by alarming symptoms such as chest pain and dysphagia, diagnosis should be made as soon as possible. In this study we assessed the diagnostic delay, if any, in patients with the nutcracker esophagus. Moreover, we were interested in whether the abnormalities described in the distal esophagus could also involve the entire viscus. Fifty-four subjects (age range 23-78 yr) with the nutcracker esophagus were assessed for clinical and manometric variables as an overall group and after dividing them into subgroups according to their symptoms. The manometric variables were compared with those obtained in 61 controls (age range 21-67 yr). Overall, a diagnosis of nutcracker esophagus was made after an average period of 36 +/- 6 months, and surprisingly, this was not different in the various subgroups complaining of either chest pain, dysphagia, or both. Analysis of manometric variables showed that the mean amplitude of contractions was significantly higher in the patients' group at all esophageal body levels, even in the proximal portions. Again, there were no significant differences among the subgroups of nutcracker esophagus with respect to the symptoms. Notwithstanding the presence of alarming symptoms, such as chest pain and dysphagia, the nutcracker esophagus is diagnosed on average after 3 years from the onset of symptoms. Manometric assessment seems to confirm that this entity may indeed represent a primary esophageal motor disorder. The major dysfunction is due to an abnormal increase of contraction amplitude of the entire esophageal body.

Nifedipine and verapamil inhibit the sigmoid colon myoelectric response to eating in healthy volunteers.

BACKGROUND: Constipation is not an infrequent side effect complained of by patients taking calcium channel blockers. This effect may reduce patients' compliance and yield potentially serious consequences. However, the underlying mechanisms for constipation caused by such compounds are not known. AIMS: The purpose of the present study was to assess the effects of nifedipine and verapamil on the sigmoid myoelectric response to eating, a physiologic test of colonic motor function. SUBJECTS AND METHODS: Nine healthy male volunteers with no previous abdominal surgery were recruited for the study and underwent three paired studies at two-week intervals. Myoelectric sigmoid activity was recorded by means of two clip electrodes introduced within the viscus without preparation for 30 minutes basally and 90 minutes postprandially. Each study was preceded by placebo, nifedipine (20 mg), or verapamil (120 mg). RESULTS: Analysis of the tracings revealed that nifedipine strongly inhibited the sigmoid myoelectric response to the meal. This response was also significantly reduced in those taking verapamil compared with the placebo group, although to a much lesser extent than in those taking nifedipine. CONCLUSIONS: We conclude that constipation as a result of some calcium channel blockers may be caused by inhibition of colonic motor activity by nifedipine and, to a lesser extent, by verapamil. The latter compound probably displays other mechanisms (reduced colonic transit, increased water absorption) also responsible for this side effect.

Effects of octreotide on manometric variables in patients with neuropathic abnormalities of the small bowel.

At present, there are few therapeutic options in patients with chronic intestinal dysmotilities. Octreotide, a long-acting somatostatin analog, has recently been shown to be a potentially useful drug in this setting, being able to start activity fronts (AF) in the small bowel in both healthy subjects and patients with intestinal motor disorders. We studied the effects of octreotide on manometric variables in 10 patients with chronic upper gastrointestinal symptoms and an intrinsic neuropathic disorder of the small intestine. Gastrointestinal manometry was carried out for 6 hr during fasting and 2 hr after a standard 605-kcal mixed meal. Thereafter octreotide, 50 micrograms subcutaneously was administered and the recording session continued for a further hour. Analysis of the tracings during fasting showed that 44% of the AF were abnormal; octreotide significantly increased the hourly number of AF (2 +/- 0.26 vs 0.67 +/- 0.14, P < 0.0001) and their duration (8.33 +/- 1.3 vs 6.12 +/- 0.34 min, P < 0.05) with respect to the baseline (fasting) period, and the propagation velocity also significantly slowed (3.4 +/- 0.4 vs 11 +/- 0.6 cm/min, P < 0.05). After the drug, 80% of patients displayed two AF and 10% more than two AF; the first AF after octreotide was always abnormally propagated. An almost complete inhibition of small bowel postprandial contractile activity was observed in 80% of patients, and the remaining 20% showed decreases. In three subjects, octreotide injection evoked the appearance of pylorospasm. From these results we conclude that octreotide could be of some benefit in patients with neuropathic disorders of the small bowel, although it remains to be established whether it is most useful in patients with more severe conditions, characterized by the complete absence of AF. The appearance of pylorospasm may contribute to the delayed gastric emptying observed after the drug is administered.