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Biomedical subjects

D F Altomare

Publications and source records attributed to D F Altomare.

At least 19 recordsLinked to original sources

Tissue factor and vascular endothelial growth factor expression in colorectal cancer: relation with cancer recurrence.

OBJECTIVE: This study was undertaken to quantify tissue factor (TF) and vascular endothelial growth factor (VEGF) in colorectal cancer and to evaluate their possible relationship with recurrence. METHOD: TF and VEGF were measured by enzyme-linked immunosorbent assay in surgical tumour specimens and normal mucosa from 50 consecutive patients with colorectal cancer who were followed up for 3 years for the assessment of disease recurrence. RESULTS: TF and VEGF antigens were detected in all tumour samples. VEGF, but not TF, was much higher in tumour than in normal mucosa (P < 0.0001), as also confirmed by measurement of specific mRNAs. There was a strong correlation between TF and VEGF antigens (P < 0.0005) in tumour tissue but not in normal mucosa. Neither protein was related to tumour stage, grade or size. Local or distant recurrence was statistically related to pTNM stage. High VEGF, but not TF, levels in tumour extracts were associated with an increased risk of recurrence both by univariate (RR, 4.00, 95% CI: 1.45-11.0) and multivariate analyses (RR, 3.65, 95% CI: 1.33-10.0). CONCLUSION: These findings suggest that VEGF content in colorectal cancer is an independent risk factor for tumour recurrence and might help select patients who might benefit from adjuvant therapy.

Colorectal Neoplasms↗

Increased farnesyltransferase activity in human colorectal cancer: relationship with clinicopathological features and K-ras mutation.

BACKGROUND: The enzyme farnesyltransferase has emerged as an important target for anti-cancer therapies. Farnesyltransferase inhibitors have been introduced in clinical trials of subjects with colorectal cancer. We investigated Farnesyltransferase activity, beta-subunit Farnesyltransferase protein expression and its mRNA in patients with colorectal cancer and its relationship with clinicopathological features and K-ras mutation. METHODS: Farnesyltransferase activity was determined by Farnesyltransferase [3H] SPA enzyme assay. Beta-subunit Farnesyltransferase protein expression was investigated by Western blotting and its mRNA by reverse transcriptase-polymerase chain reaction. K-ras mutation was detected by polymerase chain reaction amplification and restriction enzyme analysis. Multiple linear regression analysis was used to analyse relationships among age, sex, site of tumour, Dukes' stage, histological differentiation, K-ras mutation and Farnesyltransferase activity in normal mucosa and cancer. RESULTS: The levels of Farnesyltransferase activity and beta-subunit Farnesyltransferase protein expression were significantly higher in cancer than in normal mucosa. Moreover, tumours located on the right side, with mucinous histological differentiation and with K-ras mutation showed higher levels of Farnesyltransferase activity. CONCLUSIONS: Our findings suggest that Farnesyltransferase activity may be a potential marker of tumourigenicity. The differences in Farnesyltransferase activity in relation to histological grading, tumour location and K-ras mutation described here may constitute a starting point for investigating the causes of this variation within the large bowel.

Adenocarcinoma↗

Short-term sacral nerve stimulation for functional anorectal and urinary disturbances: results in 40 patients: evaluation of a new option for anorectal functional disorders.

PURPOSE: There are several options in the treatment of fecal incontinence; it is often difficult to choose the most appropriate, adequate treatment. The consolidated experience gained in the urologic field suggests that sacral nerve stimulation may be a further option in the choice of treatment. The aim of our study was to evaluate the preliminary results of the peripheral nerve evaluation test obtained in a multicenter collaborative study on patients with defecatory and urinary disturbances. METHODS: Forty patients (9 males; mean age, 50.2; range, 26-79 years) underwent the peripheral nerve evaluation test, 28 (70 percent) for fecal incontinence and 12 (30 percent) for chronic constipation. Fourteen (35 percent) patients also had urinary incontinence; six had urge incontinence, two had stress incontinence, and six had retention incontinence. Associated diseases were scleroderma (2 patients), spinal injuries (4 patients), and syringomyelia (1 patient). All the patients underwent preliminary investigations with anorectal manometry, pudendal nerve terminal motor latency testing, anal ultrasound, defecography, and if required, urodynamic tests. The electrode for sacral nerve stimulation was positioned percutaneously under local anesthesia in the S2 (4), S3 (34), or S4 (1) foramen unilaterally (1 patient not accounted for because of no response to acute test), based on the best motor and subjective responses of paresthesia of the pelvic floor. Stimulation parameters were average amplitude, 2.8 (range, 1-6) V and average frequency, 15 to 25 Hz. RESULTS: The mean duration of the tests was 9.9 (range, 7-30) days; tests lasting fewer than seven days were not evaluated. There were four early displacements of the electrode. In 22 of the 25 evaluable patients with fecal incontinence, there was an improvement of symptoms (88 percent), and 11 (44 percent) were completely continent to liquid or solid stools, whereas in 7 symptoms were unchanged. Mean number of episodes of liquid or solid stool incontinence per week was 8.1 (range, 4-18) in the prestimulation period and 1.7 (range, 0-12) during the peripheral nerve evaluation test. (P = 0.001; Wilcoxon's signed-rank test). The most important manometric findings were: increase of maximum rest pressure (39.4 +/- 7.3 vs. 54.3 +/- 8.5 mmHg; P = 0.014, Wilcoxon's test) and maximum squeeze pressure (84.7 +/- 8.8 vs. 99.5 +/- 1.1 mmHg; P = 0.047), reduction of initial threshold (63.6 +/- 5.2 vs. 42.4 +/- 4.7 ml; P = 0.041) and urge sensation (123.8 +/- 0.6 vs. 78.3 +/- 8.9 ml; P = 0.05). An improvement was also found in patients with constipation, with reduction in difficulty emptying the rectum, with prestimulation at 7 (range, 2-21) episodes per week and end of peripheral nerve evaluation test at 2.1 (range, 0-6) episodes per week, P < 0.01) and in the number of unsuccessful visits to the toilet, which dropped from 29.2 (7-24) to 6.7 (0-28) per week (P = 0.01). The most important manometric findings in constipated patients were an increase in amplitude of maximum squeeze pressure during sacral nerve stimulation (prestimulation, 63 +/- 0 mm Hg; end of peripheral nerve evaluation test, 78 +/- 1 mm Hg; P = 0.009) and a reduction in rectal volume for urge threshold (prestimulation, 189 +/- 52 ml; end of peripheral nerve evaluation test, 139 +/- 45 ml; P = 0.004). CONCLUSIONS: In functional bowel disorders short-term sacral nerve stimulation seems to be a useful diagnostic tool to assess patients for a minor invasive therapy alternative to conventional surgical procedure.

Adult↗

Neuromodulation for fecal incontinence: outcome in 16 patients with definitive implant. The initial Italian Sacral Neurostimulation Group (GINS) experience.

PURPOSE: Sacral nerve modulation appears to offer a valid treatment option for some patients with fecal incontinence and functional defects of the internal anal sphincter or of the striated muscle. METHODS: Sixteen patients with fecal incontinence (4 males; mean age, 51.4 (range, 27-79) years) with intact or surgically repaired (n = 1) anal sphincter underwent permanent sacral nerve stimulation implant. Cause was traumatic in two patients, and associated disorders included scleroderma (2 patients) and spastic paraparesis (1 patient); eight (50 percent) of the patients also had urinary incontinence, and two (12.5 percent) had nonobstructive urinary retention. All patients were selected on the basis of positive findings from at least one peripheral nerve evaluation. The stimulating electrode was positioned in the S2 (1 patient), S3 (14 patients), or S4 (1 patient) sacral foramen. RESULTS: Mean follow-up was 15.5 (range, 3-45) months. Mean preimplant Williams score decreased from 4.1 +/- 0.9 (range, 2-5) to 1.25 +/- 0.5 (range, 1-2) (P = 0.01, Wilcoxon test), and the number of incontinence accidents for liquid or solid stool in 14 days decreased from 11.5 +/- 4.8 (range, 2-20) before implant to 0.6 +/- 0.9 (range, 0-2) at the last follow-up. Important manometric data were an increase in mean maximal pressure at rest of 37.7 +/- 14.9 mmHg (implantable pulse generator 49.1 +/- 18.7, P = 0.04) and in mean maximal pressure during squeeze (prestimulation 67.3 +/- 21.1 mmHg, implantable pulse generator 82.6 +/- 21.0, P = 0.09). CONCLUSIONS: Neuromodulation can be considered an option for fecal incontinence. However, an accurate clinical and instrumental evaluation and careful patient selection are required to optimize outcome.

Adult↗

Contribution of posture to the maintenance of anal continence.

The anorectal angle (ARA) is believed to provide one of the most important contributions to anal continence. The normal resting angle is approx. 90 degrees, but the erect position may modify the ARA and other parameters usually considered in a proctometrogram. We compared the proctometrogram in different postures to elucidate the role of changes in the ARA in maintaining fecal continence. Sixty-three patients with constipation underwent static proctography. Variations in the ARA, perineal descent, puborectalis muscle length, and pubococcygeal distance were determined during resting, squeezing, and pushing with the patient in the Sims' position (SP); further evaluations used radiographs in resting position but with straight legs, in erect and sitting positions. The resting mean ARA was 95.3 +/- 15 degrees in SP and 79.8 +/- 14 degrees standing erect; the latter value was also significantly less during squeezing (84 +/- 11 degrees). The mean ARA during pushing was 118 +/- 16 degrees. A systematic and statistically significant difference in the mean resting ARA was demonstrated using the baseline of the rectal shape instead of the major rectal axis when measuring the anorectal angle. When sitting on a toilet, the mean resting ARA was significantly wider than in SP. The length of the puborectalis sling at rest did not change but was significantly reduced during squeezing and increased during pushing. The descent of the perineum at rest was near to 0 (-0.089 +/- 1.76 cm) in SP and significantly less when standing (-0.65 +/- 1.9 cm) and during squeezing (-0.97 +/- 1.7 cm). Perineal descent during pushing was +2.94 +/- 2.2 cm. The mean pubococcygeal distance did not change significantly in SP and in the erect position. The erect position thus contributes significantly to the maintenance of fecal continence by sharpening the ARA. This effect is stronger than any active contraction of the puborectalis muscle and is not related to shortening of the puborectalis sling but is secondary to lifting of the pelvic floor.

Adult↗

Chilaiditi's syndrome. Successful surgical correction by colopexy.

We describe the case of a patient affected by the Chilaiditi's syndrome, the interposition of the small or large bowel between the inferior face of the diaphragm and the liver, a rare anomaly, often asymptomatic. A 50-year-old man came to our outpatients clinic because of persistent pain in the right abdominal region. Two attempts to perform colonoscopy failed because of the impossibility of passing through the transverse colon. A double contrast enema indicated only sigmoid diverticulitis. Only after abdominal radiography was the abnormal position of the right colon noted. At surgery the right colon was totally intraperitoneal and positioned between the diaphragm and liver, which was smaller than normal. The right colon was repositioned and fixed to the anterior abdominal wall. The postoperative course was uneventful and the right abdominal pain disappeared completely. In conclusion, surgical treatment of Chilaiditi's syndrome may be required in cases of persistent abdominal pain.

Colon↗

Prospective randomized multicentre trial comparing stapled with open haemorrhoidectomy.

BACKGROUND: The aim of this study was to compare the results of conventional open haemorrhoidectomy as currently practised in Italy (group 1) with stapled haemorrhoidectomy using a 33-mm circular stapling device (group 2). METHODS: One hundred patients with symptomatic third- and fourth-degree haemorrhoids were enrolled by five hospitals. Patients were allocated to the two groups according to a centralized randomization scheme featuring five permutated blocks of 20. Preoperative clinical examination and anorectal manometry demonstrated no features of anal incontinence. Patients had a clinical and manometric re-evaluation after operation and were asked to complete a clinical diary. After a median of 16 (range 8-19) months patients were administered a standardized questionnaire by telephone. RESULTS: Postoperative bleeding requiring haemostatic procedures occurred in three patients in each group. Patients in group 1 complained of moderate pain for a median of 5.3 (range 0-19) days compared with 3.1 (range 0-10) days in group 2 (P = 0.01), while severe pain was present for 2.3 (range 0-24) days in group 1 but only for 1 (range 0-14) day in group 2 (P = 0.03). The median hospital stay was 2 days in group 1 compared with 1 day in group 2 (P = 0.01). In the early days after operation, patients in group 2 had greater difficulty in maintaining normal continence to liquid stools (P = 0.01), but after 30 days the continence score was better in group 2 (P = 0.04). CONCLUSION: Stapled haemorrhoidectomy is as effective as conventional haemorrhoidectomy. Reduced postoperative pain, shorter hospital stay and a trend toward earlier return to work suggest short-term advantages for the stapled technique.

Adult↗

Multicentre retrospective analysis of the outcome of artificial anal sphincter implantation for severe faecal incontinence.

BACKGROUND: A new prosthetic device, the Action artificial anal sphincter, has recently been introduced for treating severe faecal incontinence. The results of this procedure in 28 patients are presented. METHODS: The patients underwent operation for severe faecal incontinence in four Italian university hospitals and patients were reviewed after a median follow-up of 19 (range 7-41) months. RESULTS: Early infections occurred in four patients, requiring removal of the device in three. Dehiscence of the perineal wound occurred in nine patients. After activation of the device, the cuff had to be removed in a further four patients (for rectal erosion in two, anal pain in one and late infection in one). The cuff was accidentally broken in one patient. A new anal cuff was repositioned successfully in two patients. Overall, five patients had complete removal of the device and two removal of the cuff only. Twenty-one patients available for long-term evaluation had a major improvement in faecal continence. Median resting anal pressure increased from 27 mmHg before surgery to 32 mmHg after operation. Preoperative squeeze pressure was 42 mmHg while maximum postoperative anal pressure with the activated device was 67 mmHg. The median American Medical System incontinence score decreased significantly from 98.5 to 5.5 (P < 0.001). Similar figures were observed using the Continence Grading Scale (from 14.9 to 2.6; P < 0.001). Twelve patients developed symptoms of obstructed defaecation while two patients complained of anal pain. CONCLUSION: Improved continence was achieved after neosphincter implantation in three-quarters of the patients. Early infection and rectal erosion, together with difficulty in evacuating, are still major concerns with this technique.

Adult↗

Long-term effects of stapled haemorrhoidectomy on internal anal function and sensitivity.

BACKGROUND: Stapled haemorrhoidectomy is gaining wide acceptance but there is still some concern about the risk of injury to the internal anal sphincter (IAS). IAS function and morphology, and anal canal sensitivity were studied prospectively in patients undergoing this operation. METHODS: Twenty patients (11 women; mean age 43 years) with stage III haemorrhoids entered the study. All underwent preoperative anorectal manometry, rectoanal inhibitory reflex (RAIR) testing and three-dimensional transanal ultrasonography. A test of anal sensation was administered to evaluate ability to discriminate between air and warm water. All the investigations were repeated 6 months after the operation. RESULTS: The mean(s.d.) maximal resting pressure was 87(30) mmHg before surgery and 81(20) mmHg afterwards (P not significant). The maximal squeeze pressure did not change after operation (178(43) versus 174(60) mmHg). The RAIR showed the same features in 19 of 20 patients before and 18 of 20 after operation. Three-dimensional ultrasonography demonstrated no changes in the width of the IAS (mean(s.d.) 2.1(4) mm before and 2.1(3) mm after surgery). The ability of the anal mucosa to discriminate air from warm water improved in five patients. Continence scores did not differ significantly after 6 months. CONCLUSION: Stapled haemorrhoidectomy does not affect the function and morphology of the IAS in the long term. The sensitivity of the anal canal can improve in patients with preoperative sensory impairment.

Adult↗

Idiopathic chronic constipation: tachykinins as cotransmitters in colonic contraction.

BACKGROUND: Tachykinins (TKs) have been shown to be involved in the excitatory enteric motor pathway. This study aimed to examine the direct and nerve-mediated effect of specific NK1, NK2 and NK3 receptor agonists and antagonists in colonic preparations from control subjects and patients with idiopathic chronic constipation (ICC). MATERIALS AND METHODS: Cumulative concentrations of Sar9Met(O2)11 substance P (selective NK1 receptor agonist), [Ala5,beta-Ala8]-neurokinin A (4-10) (selective NK2 receptor agonist) and [MePhe7]-neurokinin B (selective NK3 receptor agonist) were tested on colonic circular muscle strips to evaluate the direct drug effects. In addition, in the presence of atropine, the role of TKs in the off-contraction that follows the typical inhibitory response evoked by low frequencies of electrical field stimulation (0.5--10 Hz, 20 V, 1 ms pulse trains lasting 1 min) was investigated. RESULTS: In control preparations, the rank order of potency was: NK2 receptor-selective agonist > NK3 receptor-selective agonist > NK1 receptor-selective agonist. The off-contraction was found to be reduced by about 30--40% in colonic circular muscle from ICC patients with respect to controls. Incubation with the NK1 receptor agonist did not modify the off-contraction measurements in either control or ICC preparations. Conversely, both NK2 and NK3 receptor agonists significantly (P < 0.01) increased the off-contraction in ICC preparations only. This increased response was fully antagonized by MEN-10627, a NK2 and NK3 receptor antagonist depending on the dose. CONCLUSIONS: We may conclude that ICC is hyporesponsive to TKs and that the contractile reflex to distension is greatly reduced in ICC disease, but can be restored by incubation with NK2 and NK3 receptor agonists.

Adult↗

Glyceryl trinitrate for chronic anal fissure--healing or headache? Results of a multicenter, randomized, placebo-controled, double-blind trial.

PURPOSE: Internal anal sphincterotomy for treating chronic anal fissure can irreversibly damage anal continence. Reversible chemical sphincterotomy may be achieved by anal application of glyceryl trinitrate ointment (nitric oxide donor), which has been reported to heal the majority of patients with anal fissure by inducing sphincter relaxation and improving anodermal blood flow. This trial aimed to further clarify the role of glyceryl trinitrate in the treatment of chronic anal fissure. METHODS: A total of 132 consecutive patients from nine centers were randomly assigned to receive 0.2 percent glyceryl trinitrate ointment or placebo twice daily for at least four weeks. The severity of pain and maximum anal resting pressure were measured before and after one week of treatment. Anodermal blood flow was measured before and after application of glyceryl trinitrate or placebo in ten patients. RESULTS: The study was completed by 119 patients (59 glyceryl trinitrate and 60 placebo), matched for gender, age, duration of symptoms, duration of treatment, site of fissure, previous attempts to treat, pain score, and maximum anal resting pressure. Twenty-nine patients (49.2 percent) healed after glyceryl trinitrate and 31 patients (51.7 percent) healed after placebo (P = not significant). Pain score fell significantly in both groups, in addition to maximum anal resting pressure. Anodermal blood flow improved significantly in seven patients receiving glyceryl trinitrate, but not in the three receiving placebo. Twenty-three patients (33.8 percent) experienced headache and 4 (5.9 percent), orthostatic hypotension after glyceryl trinitrate. CONCLUSION: This trial fails to demonstrate any superiority of topical 0.2 percent glyceryl trinitrate treatment vs. a placebo, although the effects of glyceryl trinitrate on anodermal blood flow and sphincter pressure are confirmed. This finding, together with the high incidence of side-effects, should discourage the use of this treatment as a substitute for surgery in chronic anal fissure.

Adult↗

Effects of erythromycin on human colonic circular muscle in idiopathic chronic constipation.

BACKGROUND: Erythromycin has been shown to have profound prokinetic effects on the gastrointestinal tract of humans and animals, probably through its action on endogenous motilin receptors. The purpose of this study was to determine both the direct and indirect effects ('off contraction') of erythromycin and motilin on ex vivo circular muscle strips of the distal colon from patients with or without idiopathic chronic constipation (ICC). MATERIALS AND METHODS: Cumulative concentrations of erythromycin (1-20 microM) and motilin (0.05-1 microM) were tested in both control and ICC preparations in order to evaluate the direct drugs effect. A range doses of both erythromycin (0.5-10 microM) and motilin (0.05-0.5 microM) were tested on their ability to affect the off-contraction that follows the typical inhibitory response evoked by low frequencies of Electrical Field Stimulation (EFS) (1-5 Hz, 20 V, 1 msec pulse trains lasting 1 min). RESULTS: The direct effect of both erythromycin and motilin was a slight increase (less than 10% of the maximal ACh-induced contraction) in the basal tension, with no dose-response relationship. The off-contraction, evoked by EFS, was not affected by drugs pretreament in control preparations. Conversely, in ICC preparations both drugs significantly increased the off-contraction (about 30%). CONCLUSIONS: Erythromycin causes mainly an indirect contractile effect in circular muscle strips from ICC patients. This effect may be related to the activation of inhibitory neuronal motilin receptors. This activation might potentiate NANC relaxation, proportionally increasing the circumferential reflex contraction that follows the EFS-induced relaxation.

Adult↗