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Biomedical subjects

R K Phillips

Publications and source records attributed to R K Phillips.

At least 19 recordsLinked to original sources
PubMed2001

Topical phenylephrine increases anal canal resting pressure in patients with faecal incontinence.

INTRODUCTION: The internal anal sphincter receives a stimulatory alpha(1) adrenergic innervation. Use of an adrenergic agonist may therefore have a role in treating patients with faecal incontinence. METHODS: Ten patients (seven females, median age 66 years) with passive faecal incontinence related to weak internal anal sphincter were studied. All patients had intact anal sphincters as assessed by endoanal ultrasound. Phenylephrine gel was applied in a double blind manner in concentrations of 0%, 10%, 20%, 30%, and 40% (Slaco Pharma (UK) Ltd, Watford, UK) on separate days. Maximum resting anal pressure (MRP), anodermal blood flow, blood pressure, and pulse rate were measured before, and one and two hours after application. RESULTS: All concentrations of phenylephrine gel increased median MRP (43, 48, 54, 65, and 70 cm H(2)O, for placebo, 10% (p=0.122), 20% (p=0.170), 30% (p=0.002), and 40% (p=0.004), respectively at one hour; comparisons with placebo). This was sustained at two hours. There was a clear dose-response relationship at one hour. Higher concentrations raised median MRP to within the normal range (> 60 cm H(2)O). At two hours, all concentrations greater than 20% increased the pressure to a similar degree, suggesting that the exact concentration may be important for the initial effect but given a certain threshold is less important after a period of time. Toxicity was rare. Two patients experienced transient perianal burning which settled within a few minutes. There was no significant effect on anodermal blood flow, blood pressure, or pulse rate. CONCLUSION: This study has demonstrated the feasibility of using topical phenylephrine to raise resting anal tone in patients with faecal incontinence. Randomised controlled trials are required to assess the efficacy of this agent.

Administration, Topical↗
PubMed2000

Persistent pain and faecal urgency after stapled haemorrhoidectomy.

INTRODUCTION: Haemorrhoidectomy usually cures haemorrhoids. Day surgery is feasible, and is associated with high patients' satisfaction and few complications, but patients take an average of 2 weeks off work after surgery. Stapled haemorrhoidectomy has the potential to decrease postoperative pain and time off work. However, data on long-term efficacy and function are lacking. METHODS: 22 patients underwent stapled haemorrhoidectomy: seven in a pilot study, and 15 in a randomised controlled trial to compare the new stapled operation with diathermy haemorrhoidectomy in a day-case setting. All operations were done by one consultant surgeon. RESULTS: 16 patients were followed up for longer than 6 months, five of whom (31% [95% CI 8.5-54.0%]) developed symptoms of pain and faecal urgency which persisted for up to 15 months postoperatively. The randomised trial was suspended, and patients were investigated with endoanal ultrasonography, anorectal physiology, and examination under anaesthetic. All five affected patients were reviewed by two independent surgeons experienced in the stapled operation. In one patient, a fibroepithelial polyp was found adjacent to an anodermal ulcer; in the other patients, no abnormality was found. Four of the five affected patients had some muscle incorporated into the doughnut, compared with only one of 11 of the unaffected patients (p=0.012, Fisher's exact test). No other significant differences in operative variables were identified between patients with and without symptoms. INTERPRETATION: Persistent severe pain and faecal urgency has been found in a disturbingly high proportion of patients after stapled haemorrhoidectomy. The mechanism behind this phenomenon is unclear, although muscle incorporation in the doughnut may have a role. Other groups who have studied stapled haemorrhoidectomy urgently need to audit their long-term results to assess the frequency of this problem.

Adult↗
PubMed2000

The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. METHODS: We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. RESULTS: At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. CONCLUSIONS: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.

Adenomatous Polyposis Coli↗
PubMed2000

Randomized, controlled trial of topical phenylephrine for fecal incontinence in patients after ileoanal pouch construction.

INTRODUCTION: Fecal incontinence is experienced by some patients with an ileoanal reservoir pouch. The alpha1-adrenergic agonist phenylephrine raises resting anal sphincter pressure in healthy volunteers and may be of value in these patients. METHODS: Twelve patients (7 female), median age 44 (range, 29-67) years were studied. All had fecal incontinence despite a noninflamed pouch of normal size and ultrasonographically structurally normal anal sphincter muscles. Patients were treated with topical 10 percent phenylephrine and placebo gels, allocated in random order in a double-blind, crossover study for two four-week periods. Before and during treatment, maximum resting anal sphincter pressure and anodermal blood flow were measured, a symptom questionnaire was completed, and incontinence score was determined using a validated scale. RESULTS: Six of 12 (50 percent) patients improved subjectively after phenylephrine compared with one on placebo (P = 0.07). Four patients had complete cessation of incontinence with active treatment. Phenylephrine significantly reduced the incontinence score (P = 0.015). It also resulted in a significant rise in mean maximum resting anal sphincter pressure when compared with placebo (P = 0.012). For all 12 patients, mean percent subjective improvement was higher after phenylephrine compared with placebo (P = 0.04). There were no side effects. CONCLUSIONS: Topical phenylephrine significantly improves fecal continence in patients with an ileoanal pouch. In some patients it totally eliminates nocturnal episodes. The mechanism of benefit is likely to be one of altered neural sphincter control. This is the first study of the use of a topical pharmacologic agent to treat fecal incontinence and may have a wider application.

Administration, Topical↗
PubMed2000

Topical diltiazem and bethanechol decrease anal sphincter pressure and heal anal fissures without side effects.

PURPOSE: Topical glyceryl trinitrate heals anal fissures, but a majority of patients experience headache. Topical gels of the calcium channel blocker diltiazem and the cholinomimetic bethanechol significantly lower anal sphincter pressure in volunteers. This study investigated the use of these two new pharmacologic agents in the treatment of patients with chronic anal fissure. METHODS: Two studies were conducted, each involving 15 patients with chronic anal fissure. In each study patients underwent anal manometry and laser doppler flowmetry before treatment. They were treated with either 2 percent diltiazem gel or 0.1 percent bethanechol gel three times daily for eight weeks. Assessment every two weeks was by clinical examination, repeat anal manometry, and laser doppler flowmetry. Daily pain was assessed by linear analog charts. RESULTS: Fissures healed in 10 of 15 (67 percent) patients treated with 2 percent diltiazem gel and in 9 (60 percent) patients treated with 0.1 percent bethanechol gel. There was no significant difference in the pretreatment maximum resting sphincter pressure (MRP) between responders and nonresponders in either group. There was significant reduction in the pain score after treatment with diltiazem (P = 0.002) and bethanechol (P = 0.005) compared with that before treatment. MRP was significantly lower after diltiazem (P = 0.0001) and bethanechol (P = 0.02) compared with pretreatment MRP. No headaches or side effects were reported. CONCLUSIONS: Both topical diltiazem and bethanechol substantially reduce anal sphincter pressure and achieve fissure healing to a similar degree reported with topical nitrates, but without side effects.

Administration, Topical↗
PubMed2000

Telomere length in familial adenomatous polyposis-associated desmoids.

PURPOSE: The aim of this study was to establish the length of telomeres in familial adenomatous polyposis-associated desmoids. METHODS: DNA from 21 desmoids and five desmoid precursor lesions was digested with HinfI and RsaI restriction enzymes. Southern blotting of the resolved fragments was performed, and the membranes were hybridized with a specific probe attached to a chemiluminescent substrate. Terminal restriction fragment lengths were measured. RESULTS: The median terminal restriction fragment length for the desmoids was 8 (range, 6-9.6) vs. 7.7 (range, 6.4-9.9) kb for their controls. Median terminal restriction fragment length for the desmoid precursor lesions was 9 (range, 7.8-10.4) vs. 8.8 (range, 6.8-10.9) kb for their controls. There was no statistically significant difference between samples and their controls. CONCLUSION: Immortality may not be necessary for desmoid development, or there may be other mechanisms maintaining telomere length. Novel treatments involving telomerase inhibition will be inappropriate in the management of desmoids.

Abdominal Neoplasms↗
PubMed2000

Adrenal masses are associated with familial adenomatous polyposis.

PURPOSE: Although its defining feature is the development of multiple large-bowel polyps, familial adenomatous polyposis is a generalized disorder of tissue growth regulation, with a range of manifestations. An association between adrenal neoplasms and familial adenomatous polyposis has been suggested, but not prospectively documented. Patients with familial adenomatous polyposis were therefore screened to determine the frequency of adrenal masses. METHODS: Patients with familial adenomatous polyposis underwent spiral abdominal CT scan reported by two radiologists specialized in cross-sectional imaging. RESULTS: One hundred seven individuals were examined (median age, 36 (interquartile range, 30-48) years; 57 male). Fourteen (13 percent) had an adrenal mass of 1 cm or greater (bilateral in one case); none had clinical evidence of endocrine disturbance or hypertension. Two lesions were histologically confirmed adrenocortical adenomas and one a phaeochromocytoma; the remaining 12 had CT appearances of nonhyperfunctioning adrenocortical adenoma. CONCLUSIONS: The prevalence of unsuspected adrenal masses in the general population is approximately three percent. This prospective study found a significantly higher frequency of 13 percent in patients with familial adenomatous polyposis (chi-squared = 6.973; df = 1; P = 0.008). There is no evidence that the histologic nature of these differs from that in the general population.

Adenomatous Polyposis Coli↗
PubMed2000

Surgery for large intra-abdominal desmoid tumors: report of four cases.

PURPOSE: Desmoids are rare, locally aggressive but nonmetastasizing fibrous masses that occur sporadically and in association with familial adenomatous polyposis. Therapeutic options are limited, and there is reluctance to operate on mesenteric desmoids because of the risk of complications or recurrence. Consequently, there is an increasing reliance on alternative therapeutic modalities. Nonsurgical options are of variable efficacy, however, and surgery is still required for the complications of desmoids. Each of the last four patients with desmoids presenting to this unit has required life-saving surgery as a result of failure of nonsurgical treatments or the development of complications. METHODS: We present case reports of four consecutive patients with large mesenteric desmoid tumors requiring surgical management. RESULTS: All four patients had massive mesenteric desmoids. Three cases associated with familial adenomatous polyposis had developed their desmoids after colectomy while the sporadic desmoid had continued to grow rapidly after diagnosis at laparotomy. Sulindac and toremifene were unsuccessful in all cases and one patient with familial adenomatous polyposis suffered dramatic erosion of her desmoid through the abdominal wall during antisarcoma chemotherapy. Two others required emergency laparotomy for complications, and the sporadic case underwent elective resection for symptomatic relief. Three had complete excision of their desmoid, and all remained well with no recurrence at a median follow-up of 12 (range, 7-14) months. CONCLUSION: Despite the risks, there remains a role for surgery in the management of large mesenteric desmoids.

Adolescent↗
PubMed2000

New, simple approach for maximal pudendal nerve exposure: anomalies and prospects for functional reconstruction.

PURPOSE: Functional neosphincters after pudendal nerve anastomosis proved possible in animal models and may be applicable in humans, but access is a recognized problem. We report the occurrence of pudendal nerve anomalies, its implications for reconstruction, and describe a new approach for maximal exposure. METHODS: Adult human cadavers were positioned prone and dissected via a gluteal approach. Pudendal nerve variations and physical measurements were analyzed statistically. RESULTS: A new, simple, four-step approach (surface landmarks and exposure of gluteus maximus muscle, sacrotuberous ligament, and pudendal neurovascular bundle) permitted optimal pudendal nerve exposure in all 14 human cadavers (28 limbs). Six were males and had a mean age of 82 (range, 58-102) years. Two anomalies, Type 1 (2-trunked) and Type 2 (3-trunked), of the pudendal nerve were recognized in 30 percent of cadavers, with a left-to-right ratio of 2.5:1. Mean pudendal nerve length over the ischial spine was 23.9 (range, 19-28) mm right, 24.2 (range, 19-28) mm left (P = 0.54), but its diameter measured 5.2 mm (right) and 4.9 mm (left; P = 0.04). Mean length of pudendal nerve trunk exposed after reflection of the sacrotuberous ligament was 55 (range, 44-75) mm on either side before division into terminal branches. The number and percent frequency of inferior rectal nerve on both sides were 1 (13 percent), 2 (76 percent), and 3 (11 percent), respectively, with a mean length of 27.1 (range, 21-34) mm right and 27.9 (range, 20-33) mm left (P = 0.31). CONCLUSION: A simple four-step approach to the pudendal nerve contributes to improved access in all cases. It facilitates reconstruction because it allows accurate nerve selection and recognition of potential anomalies that might influence functional outcome.

Aged↗
PubMed2000

Familial adenomatous polyposis complicated by an intrahepatic desmoid tumor: report of a case.

Desmoids are uncommon proliferations of fibroblasts that occur with disproportionate frequency in patients with familial adenomatous polyposis. They do not metastasize and are histologically benign. Despite this, the unpredictable and often aggressive nature of familial adenomatous polyposis-associated desmoids and their tendency to occur in intra-abdominal sites means that they present a difficult management problem, and they are a leading cause of death in patients with familial adenomatous polyposis who have undergone colectomy. We report a case of a patient with familial adenomatous polyposis who had extensive and aggressive desmoid disease and whose management was further complicated by a large intrahepatic desmoid. There are no previous reports of desmoids occurring in the liver.

Adenomatous Polyposis Coli↗
PubMed2000

Randomized controlled trial of topical phenylephrine in the treatment of faecal incontinence.

BACKGROUND: Anal incontinence due to internal sphincter dysfunction is not amenable to simple surgical repair. The alpha-adrenergic agonist phenylephrine produces contraction of the internal sphincter and raises resting pressure when applied topically in healthy volunteers. The effect of topical phenylephrine in the treatment of faecal incontinence due to internal sphincter dysfunction was investigated. METHODS: Thirty-six patients (22 women) aged 28-81 (mean 58) years with faecal incontinence and ultrasonographically structurally normal anal sphincter muscles were treated with topical 10 per cent phenylephrine and placebo gels, allocated in random order in a double-blind crossover study. Maximum resting anal sphincter pressure and anodermal blood flow were measured. A symptom questionnaire was completed and incontinence score determined using a validated scale. RESULTS: There were no significant differences in incontinence score, resting anal pressure and anodermal blood flow between the active and placebo treatments. Six patients on active treatment and two on placebo experienced more than 75 per cent subjective improvement. Three patients developed allergic dermatitis to phenylephrine. CONCLUSION: This is the first study of the use of a topical pharmacological agent to treat faecal incontinence. This concentration of topical phenylephrine did not produce a significant improvement in symptoms or function. A subgroup of patients may respond. Further studies are required with increased concentrations.

Administration, Topical↗
PubMed2000

Functional outcome after restorative panproctocolectomy for ulcerative colitis decreases an otherwise enhanced quality of life.

BACKGROUND: Restorative panproctocolectomy is a favoured operation for ulcerative colitis, but altered bowel habit may adversely affect overall quality of life. METHODS: Specific and generic quality of life questionnaires and an instrument to award money for continuing disability based on government guidelines were sent to 103 patients who had curative surgery for ulcerative colitis between 1995 and 1997. Seventy-one patients returned completed questionnaires: 30 with an ileostomy (representing incontinence and abnormal body image), 11 with a Koch pouch (representing continence and abnormal body image) and 30 with a pelvic pouch (representing continence and normal body image). RESULTS: Patients valued the disability of having an ileostomy similar to that for a Koch pouch or a pelvic pouch: pound 40 000, pound 30 000 and pound 40 000 respectively (P = 0. 97). There was no sex difference. Body image measured with a visual analogue scale (least = 1, worst = 10) was worst with the ileostomy and Koch pouch (8 each) and best with a pelvic pouch (5) (P = 0.06). However, pelvic pouches scored significantly worse than an ileostomy with regard to altered bowel emptying (pelvic pouch, 8; Koch pouch, 7; ileostomy, 5) (P = 0.01). CONCLUSION: Poor function after pelvic pouch surgery offsets any advantage in body image over an ileostomy. Thus, overall quality of life and perceived monetary damage were the same for the two operations. Improved pelvic pouch function is likely to be reflected in better quality of life after restorative panproctocolectomy.

Adult↗
PubMed2000

Experimental study of faecal continence and colostomy irrigation.

BACKGROUND: Colostomy irrigation is a useful method of achieving faecal continence in selected conditions, but remains largely underutilized because it is time consuming. This study investigated the effect of modifying irrigation technique (route, infusion regimen and pharmacological manipulation) on colonic emptying time in a porcine model. METHODS: An end-colostomy and caecostomy were fashioned in six pigs. Twenty markers were introduced into the caecum immediately before colonic irrigation. Irrigation route (antegrade or retrograde), infusion regimen (tap water, polyethylene glycol (PEG), 1.5 per cent glycine) and pharmacological agent (glyceryl trinitrate (GTN) 0.25 mg/kg, diltiazem 3.9 mg/kg, bisacodyl 0.25 mg/kg) were assigned to each animal at random. Colonic transit was assessed by quantifying cumulative expelled markers (CEM) and stool every hour for 12 h. RESULTS: Mean CEM at 6 h for bisacodyl, GTN and diltiazem were 18.17, 12.17 and zero respectively; all pairwise differences in means were significant (P < 0.001). The difference at 12 h between the two routes (P = 0.001) and three fluids (tap water 6.75, glycine 14.83, PEG 16.33; P < 0. 001) was significant, but not for PEG versus glycine and bisacodyl versus GTN. Cumulative output was significantly more with the antegrade than retrograde route using PEG, but the difference in mean cumulative output for bisacodyl and GTN at 12 h was not significant. CONCLUSION: Colonic emptying is more efficient with antegrade than retrograde irrigation. PEG and glycine enhance emptying similar to bisacodyl and GTN solution. These findings show promise for improved faecal continence by colostomy irrigation and may justify construction of a Malone conduit at the time of colostomy in selected patients who wish to irrigate. Presented in part to the British Society of Gastroenterology in Glasgow, UK, March 1999, and published in abstract form as Gut 1999; 44(Suppl 1): A135

Analysis of Variance↗
PubMed2000

Experimental model of anorectal transplantation.

BACKGROUND: Anorectal transplantation with pudendal nerve anastomosis after rectal excision is a possible strategy that would avoid a colostomy and recreate potentially normal anorectal function. This study investigates the technical feasibility of anorectal transplantation with pudendal nerve and inferior mesenteric artery and vein anastomosis in a porcine model. METHODS: Four female pigs (22-42 kg) provided donor anorectum for four male recipients (29-39 kg) under standard general anaesthesia. The donor operation involved abdominoperineal excision of rectum (APR) taking the anal sphincter, pudendal neurovascular bundle and inferior mesenteric vessels. The recipient underwent APR, transperineal introduction of the donor graft, anastomoses of the rectum, inferior mesenteric vessels and pudendal neurovascular bundle, and perineal closure. Recorded variables were duration of each step of transplantation, ischaemic time, dimensions of anastomosed structures and postoperative graft viability. Animals were killed at 24 h, the state of the graft was noted and tissue was taken for confirmatory histology. RESULTS: Mean operation time was 372 (range 303-435)min. Mean ischaemic time was 118 (100-130)min. Before death, observation at laparotomy revealed two pink grafts, one slightly dusky but healthy graft and one outright failure, reflecting the state of the mesenteric vessels, which were patent in three and thrombosed in one. Histological examination showed no difference between control biopsies and the three cases with satisfactory mesenteric flow. Gross ischaemia was present histologically in the failed case. CONCLUSION: Anorectal transplantation is technically feasible in a pig model. Longer-term studies are now needed to assess return of function and overcome rejection issues.

Anal Canal↗
PubMed2000

Desmoids in familial adenomatous polyposis are monoclonal proliferations.

Desmoids are poorly-understood, locally aggressive, non-metastasizing fibromatoses that occur with disproportionate frequency in patients with familial adenomatous polyposis (FAP). Their nature is controversial with arguments for and against a neoplastic origin. Neoplastic proliferations are by definition monoclonal, whereas reactive processes originate from a polyclonal background. We examined clonality of 25 samples of desmoid tissue from 11 female FAP patients by assessing patterns of X-chromosome inactivation to calculate a clonality ratio. Polymerase chain reaction (PCR) amplification of a polymorphic CAG short tandem repeat (STR) sequence adjacent to a methylation-sensitive restriction enzyme site within the human androgen receptor (HUMARA) gene using fluorescent-labelled primers enabled analysis of PCR products by Applied Biosystems Genescan II software. Twenty-one samples from nine patients were informative for the assay. Samples from all informative cases comprised a median of 66% (range 0-75%) clonal cells but from the six patients with a clonality ratio < or =0.5 comprised a median of 71% (65-75%) clonal cells. FAP-associated desmoid tumours are true neoplasms. This may have implications in the development of improved treatment protocols for patients with these aggressive tumours.

Adenomatous Polyposis Coli↗
PubMed2000

Analysis of genetic and phenotypic heterogeneity in juvenile polyposis.

BACKGROUND: Juvenile polyposis syndrome (JPS) is characterised by gastrointestinal (GI) hamartomatous polyposis and an increased risk of GI malignancy. Juvenile polyps also occur in the Cowden (CS), Bannayan-Ruvalcaba-Riley (BRRS) and Gorlin (GS) syndromes. Diagnosing JPS can be problematic because it relies on exclusion of CS, BRRS, and GS. Germline mutations in the PTCH, PTEN and DPC4 (SMAD4) genes can cause GS, CS/BRRS, and JPS, respectively. AIMS: To examine the contribution of mutations in PTCH, PTEN, and DPC4 (SMAD4) to JPS. METHODS: Forty seven individuals from 15 families and nine apparently sporadic cases with JPS were screened for germline mutations in DPC4, PTEN, and PTCH. RESULTS: No patient had a mutation in PTEN or PTCH. Five different germline mutations were detected in DPC4; three of these were deletions, one a single base substitution creating a stop codon, and one a missense change. None of these patients had distinguishing clinical features. CONCLUSIONS: Mutations in PTEN and PTCH are unlikely to cause juvenile polyposis in the absence of clinical features indicative of CS, BRRS, or GS. A proportion of JPS patients harbour DPC4 mutations (21% in this study) but there remains uncharacterized genetic heterogeneity in JPS.

Adenomatous Polyposis Coli↗