Pre-operative gastric emptying time correlates with clinical response to gastric electrical stimulation in the treatment of gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) may be of benefit in cases of gastroparesis that fail to respond to standard medical therapy. Response to this treatment is varied and prediction of clinical improvement is difficult. METHODS: This was a retrospective review and symptom questionnaire survey for all patients who underwent GES insertion in a single institution from November 2008 until May 2010 using the gastroparesis cardinal symptom index (GCSI). RESULTS: 14 out of 17 patients who had GES insertion responded to telephone or postal questionnaire. Mean pre-operative gastric emptying time was 151 min (median 146 min, range 18-318). Median follow up was 14 months (range 7-25 months). The mean reduction in GCSI score after GES insertion was 51% (13.4 vs 6.4, Z = 0.0013). Percentage reduction in GCSI correlated with pre-operative solid gastric emptying time (p = 0.0086). Two patients who responded to questionnaire required device removal, one due to a gastric perforation and the other for discomfort related to the implant and a poor clinical response. CONCLUSIONS: GES significantly improves symptoms of gastroparesis on the GCSI score. Not all patients respond equally to GES, and response may be predicted by pre-operative solid gastric emptying times.

Validity of segmental transit studies used in routine clinical practice, to characterize defaecatory disorder in patients with functional constipation.

OBJECTIVE: Segmental colonic transit can be determined by performing regional counts of radio-opaque markers on an abdominal radiograph. It has been claimed that the pattern of markers can be used to characterize the type of constipation, with a concentration of markers seen in the rectosigmoid region in patients with defaecatory disorders. The aim of our study was to examine this hypothesis in a cohort of patients with functional constipation. METHOD: Consecutive patients presenting to a specialist constipation clinic and satisfying inclusion criteria were studied. All patients had the following assessments: radio-opaque marker study performed according to a standard protocol; proforma-based symptom assessment using Likert scoring; and radioisotope defaecating proctogram. Transit study data included total transit time, rectosigmoid transit time and geometric mean of markers. Symptom scores were recorded for straining, incomplete evacuation and digitation, together with a cumulative symptom score. Evidence of outlet obstruction from the proctogram included four previously described parameters. RESULTS: A total of 108 patients with functional constipation according to the Rome criteria with a median age of 41 years were studied. Neither rectosigmoid transit time nor the geometric centre of markers could differentiate patients with a functional defaecatory disorder (FDD). There was no correlation between the pattern of marker distribution and any of the parameters denoting outlet obstruction. CONCLUSION: Our data do not support the hypothesis that assessment of segmental transit, using standard methods applicable to routine clinical practice can determine the type of constipation. In particular, patients exhibiting evidence of FDD are no more likely to have recto-sigmoid retention of markers than those without.

Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation.

BACKGROUND: The role of intestinal transporter regulation in optimising nutrient absorption has been studied extensively in rodent and cell line models but not in human subjects. AIMS: The aim of the present study was to investigate the response in vivo of zinc transporters in the human enterocyte to dietary zinc supplementation. SUBJECTS: Eighteen patients who had previously undergone ileostomy, all free of any symptoms of inflammatory bowel disease. METHODS: Subjects took a daily zinc supplement of 25 mg for 14 days in a double blind, placebo controlled, crossover trial. The effect of the supplement on expression in ileal biopsies of the zinc transporters SLC30A1, SLC30A4, SLC30A5, SLC39A1, SLC39A4, and metallothionein was measured by reverse transcription-polymerase chain reaction RT-PCR. Expression of SLC30A1, SLC30A5, and SLC39A4 was also examined by immunoblotting. RESULTS: The zinc supplement reduced SLC30A1 mRNA (1.4-fold) together with SLC30A1, SLC30A5, and SLC39A4 protein (1.8-fold, 3.7-fold, and to undetectable levels, respectively) in ileal mucosa and increased metallothionein mRNA (1.7-fold). The supplement had no effect on expression of SLC30A4 or SLC39A1 mRNA. Localisation of SLC30A5 at the apical human enterocyte/colonocyte membrane and also at the apical membrane of Caco-2 cells was demonstrated by immunohistochemistry. Commensurate with these observations in zinc supplemented human subjects, SLC30A1, SLC30A5, and SLC39A4 mRNA and protein were reduced in Caco-2 cells cultured at 200 muM compared with 100 muM zinc. CONCLUSIONS: These observations indicate that, in response to variations in dietary zinc intakes, regulated expression of plasma membrane zinc transporters in the human intestine contributes to maintenance of zinc status.

Long-term outcome of laparoscopic mesh rectopexy for solitary rectal ulcer syndrome.

OBJECTIVE: To determine the long-term outcome of laparoscopic mesh rectopexy for solitary rectal ulcer syndrome (SRUS). PATIENTS AND METHODS: A retrospective review of 11 patients who underwent laparoscopic mesh rectopexy for refractory SRUS between 1993 and 1996. All patients were followed up initially with rigid sigmoidoscopy and seven were involved in long-term evaluation (follow-up at 71-106 months, median 89 months) involving a sickness impact profile questionnaire. RESULTS: Complete endoscopic healing of the ulcer was demonstrated in all 11 patients up to one year postoperatively but one suffered recurrence later. Of seven assessed long-term, none experienced endoscopic recurrence. Six continued to enjoy a significant reduction in symptoms and an improved quality of life. One had persistent problems and demonstrated little symptomatic improvement. CONCLUSION: Laparoscopic mesh rectopexy offers a minimally invasive option for selected patients who remain severely symptomatic despite maximal conservative therapy for SRUS, with demonstrable ulcer healing and long-term improvement in symptoms and quality of life. Larger studies are required to fully evaluate its efficacy compared to 'conventional' surgical options.

Prospective audit of quality of colonoscopy in a surgical coloproctology unit.

OBJECTIVE: The aim of this study was to prospectively audit the quality of colonoscopy and patient acceptance in a Surgical Coloproctology Unit over a one-year period. PATIENTS AND METHODS: 202 consecutive colonoscopies were evaluated over a 12-month period performed by a Consultant, Specialist Registrars and Research fellows. Data where recorded for adequacy of bowel preparation, completion rate, adequacy of sedation, patient tolerance and duration of the procedure. Adequacy of bowel preparation was monitored by scoring bowel content and the percentage of bowel wall visualised. Patients completed a questionnaire to express their sedation satisfaction, discomfort during the procedure and overall satisfaction. RESULTS: The success rate of bowel preparation was 94%. Completion rate was 90% in intended full colonoscopies by the Consultant and Registrars and 74% by more junior grade endoscopists (overall 86%). The mean dose of midazolam and pethidine was higher in patients with unsatisfactory sedation than those with satisfactory sedation. The pain score was higher when trainees performed the procedure than when performed by the Consultant. Fourteen patients refused to undergo the procedure again due to procedure discomfort (n = 7), inadequate sedation (n = 2) and bowel preparation discomfort (n = 5). CONCLUSION: A high completion rate was achieved, compared with published results. However, further improvements are possible especially by improving the performance of junior endoscopists and by ensuring optimal bowel preparation. Patients' tolerance of colonoscopy was highly acceptable but may also be improved by the same methods.

Sacral nerve stimulation for faecal incontinence in the UK.

BACKGROUND: Sacral nerve stimulation (SNS) is an effective therapy for faecal incontinence. Published studies derive largely from single centres and there is a need to determine the broader applicability of this procedure. METHODS: Prospective data were collected for all patients undergoing SNS in the UK. Records were reviewed to determine the outcome of treatment. RESULTS: In three UK centres 59 patients underwent peripheral nerve evaluation, with 46 (78 per cent) proceeding to permanent implantation. Of these 46 patients (40 women) all but two had improved continence at a median of 12 (range 1-72) months. Faecal incontinence improved from a median (range) of 7.5 (1-78) to 1 (0-39) episodes per week (P < 0.001). Urgency improved in all but five of 39 patients in whom ability to defer defaecation was determined, improving from a median of 1 (range 0-5) to 10 (range from 1 to more than 15) min (P < 0.001). Maximum anal squeeze pressure and sensory function to rectal distension changed significantly. Significant improvement occurred in general health (P = 0.024), mental health (P = 0.008), emotional role (P = 0.034), social function (P = 0.013) and vitality (P = 0.009) subscales of the Short Form 36 health survey questionnaire. There were no major complications. One implant was removed. CONCLUSION: SNS is a safe and effective treatment, in the medium to long term, for faecal incontinence when conservative treatment has failed.

Outcome after transperineal mesh repair of rectocele: a case series.

PURPOSE: This study was designed to establish the safety and efficacy of transperineal mesh repair in patients with obstructed defecation caused by rectocele. METHODS: Between 1998 and 2002, 24 consecutive females with symptomatic rectocele were retrospectively reviewed after mesh repair of rectocele. Two patients had inadvertent rectal perforation during operation and had no mesh implantation. Of the remaining 22 patients, 14 had a prolene mesh implanted, and 8 had a Vipro II mesh implanted. Median age at the time of presentation was 55 (range, 28-66) years. Patients were selected for operation based on clinical and evacuation proctogram findings. All patients complained of incomplete rectal evacuation, and the majority complained of excessive straining, constipation, and the need for vaginal/perineal digital pressure to aid defecation. Patients were followed up in clinic at six weeks, and a telephone questionnaire was performed at a median time of 12.5 (range, 3-47) months. Functional/objective outcomes were assessed for the following five symptoms preoperatively and postoperatively: excessive straining, incomplete evacuation, perineal/vaginal digital pressure, vaginal bulging, and constipation (always, usually, occasionally, never). Subjective outcomes were assessed as excellent, good, moderate, or poor. In addition, patients were asked about preexisting and postoperative dyspareunia. RESULTS: Objective outcomes based on symptoms showed an improvement in two or more symptoms in 20 patients (91 percent). For all symptoms, there was a significant reduction in mean values after repair. Subjective outcomes showed that 17 patients (77 percent) had a moderate/good/excellent result. Patients with abnormal preoperative colonic transit marker studies did as well as those who had no transit studies performed or those who had normal studies. Patients who did not vaginally digitate did as well as those who did not digitate. Only one patient complained of new onset dyspareunia. Two patients with sphincter defects on endoanal ultrasound had a sphincteroplasty performed (1 prerectocele repair and 1 at the same time). There were two superficial wound infections and one deep infection. All infections responded to antibiotic therapy. No mesh has been removed. Semiabsorbable mesh repair was superior to nonabsorbable mesh repair. CONCLUSIONS: Transperineal mesh repair of symptomatic rectocele is a safe technique that avoids the anal dilation and sphincter injury associated with endorectal repair. Objective and subjective results are good in the majority of patients, although a longer follow-up is required to confirm no deterioration.

Porcine dermal collagen graft in abdominal-wall reconstruction.

We describe the use of a porcine dermal collagen graft in the reconstruction of a large abdominal-wall defect in a woman. The graft was not rejected and, after 1 year, was not associated with incisional hernia. This graft may become an alternative to synthetic-mesh and flap reconstructions because, despite being of a similar tensile strength, it promotes less adhesion, is incorporated into the host tissue and is less prone to infection.

Outcome of argon beam and LASER ablation of large rectal adenomas.

OBJECTIVE: Endoscopic ablation of large rectal adenomas is being increasingly used as primary treatment. Despite the avoidance of general anaesthesia and the prevention of more major procedures, patients undergoing endoscopic ablation have the disadvantage of multiple treatment sessions and the lack of adequate tissue sample for complete histological study. The aim of this study was to analyse the outcome of all patients with large rectal polyps treated with endoscopic ablation. PATIENTS AND METHODS: Between 1993 and 1998, 29 patients who underwent endoscopic ablation of large rectal adenoma were identified. All their case notes were analysed and information was collected on recurrence, treatment episodes, complications, the incidence of carcinoma and the necessity for further procedures. RESULTS: At a median 40 (range 4-67) months follow-up, 41% of patients had recurrence of their adenoma and 14% had been diagnosed with adenocarcinoma. Only 24% of patients had been discharged while 21% were clear but were still under surveillance. Seven (24%) patients had complications, 6 stenosis and one severe bleeding. All stenosis occurred in patients who had more than 10 treatment sessions. In all, 31% of patients needed further endoanal or abdominal surgery and the median time to making this decision was 28 (range 4-66) months. There were no deaths. CONCLUSION: Laser and argon ablation of large rectal adenomas has proved very disappointing. It should be reserved for patients who are unfit to undergo general anaesthesia.

Per anal excision of large rectal adenomas using an endoscopic stapler.

Large rectal adenomas can be approached per-anally by open excision or by transanal endoscopic microsurgery (TEMS). We describe the adaptation of an endoscopic linear stapler-cutter for per anal excision of rectal polyps. It can be used for difficult polyps with minimal risk of complications and is easier and more accessible than TEMS.

Rectal retroflexion: an essential part of lower gastrointestinal endoscopic examination.

PURPOSE: Retroflexion of the endoscope during rectal examination may increase diagnostic yield but is not routinely performed because of concerns about safety and a lack of appreciation of its importance. The purpose of this study was to examine the yield, safety, and tolerance of endoscopic rectal retroflexion. METHODS: Prospective cohorts of subjects undergoing unsedated screening flexible sigmoidoscopy were examined with and without routine retroflexion. Pain scores were recorded. RESULTS: A total of 526 subjects (mean age 60 (range, 55-66) years) underwent flexible sigmoidoscopy in the first period when the endoscope was not routinely retroflexed. Of these, 480 (mean age 60 (range, 55-66) years) were subsequently examined with routine retroflexion. Retroflexion was impossible in 17 subjects (3.5 percent) because of discomfort. In the second group, 12 subjects (2.5 percent) had polyps in the lower rectum seen only on retroflexion. Of these, eight had metaplastic and four had adenomatous polyps (3 tubular <5 mm, 1 tubulovillous 15 mm). There was no difference in mean pain scores between the groups (no retroflexion = 2.13, retroflexion = 2.18). CONCLUSION: With an adenoma pick-up rate of 8 to 12 percent for screening flexible sigmoidoscopy, retroflexion increases adenoma detection by approximately 1 percent without adverse effects and should be an integral part of flexible sigmoidoscopy.

A cardiac evoked response algorithm providing automatic threshold tracking for continuous capture verification: a single-center prospective study.

BACKGROUND: The AutoCapture algorithm as implemented in Regency and Microny pacemakers (Pacesetter Inc., Sylmar, CA, USA) provides beat-by-beat monitoring of capture based on proper detection of the evoked response, provides high output back-up pulse when loss of capture occurs, performs periodic threshold evaluations and acquires the capture threshold data in a time-based event counter for later retrieval. The safety and efficacy of this algorithm was prospectively evaluated at a tertiary care hospital of north India. METHODS AND RESULTS: Fifty-four patients (38 males, mean age 66+/-13 years) received a ventricular pacemaker model Regency SC+ with low polarization bipolar lead for high-grade atrioventricular block (n=42) and sick sinus syndrome (n=12). Evoked response and polarization signal were assessed initially at 24 hours postimplant, and follow-up measurements were systematically conducted at week 1 and months 1, 3 and 6. Further evaluation of eligible patients was performed at 6-monthly intervals. Lead implantation parameters were optimum in all patients. At 6 months, the algorithm was functional in 51 patients. The pacing threshold increased to 0.89+/-0.36 V (p<0.001) in the first month and stabilized thereafter. Significant saving of energy was accomplished by a constant output safety margin of 0.3 V instead of the traditional 100%. While the evoked response signal remained stable throughout the study period, the potential signal increased significantly from 0.6+/-0.7 mV to 1.0+/-0.6 mV (p<0.001) in the first month and remained steady subsequently. Back-up pacing in the event of exit block was confirmed in all 25 patients who underwent a 24-hour Holter test. Based on the suggested sense margins, ventricular undersensing was observed in 7 (28%) patients, the majority of whom had competitive cardiac rhythms. An elderly patient with pneumonic illness succumbed to pulmonary embolism at 6 months. CONCLUSIONS: This large single-center experience on AutoCapture demonstrates the success of this algorithm in low-energy ventricular pacing without compromising the patient's safety.

Increased plasma nitrite level in cardiac failure.

Increased Plasma Nitrite Level in Cardiac Failure. Nitric oxide is implicated in the pathogenesis of cardiac failure. Plasma nitrite level (an end product of nitric oxide metabolism) is studied in 15 patients of chronic rheumatic valvular heart disease with myocardial contractile dysfunction and cardiac failure (Group I), 15 patients of chronic rheumatic valvular heart disease with similar valvular lesions, normal myocardial contractile function and without cardiac failure (Group II) and 15 healthy controls (Group III). Patients in Group I had higher nitrite level (242.2+/-31.7 n m) compared to Group II (142.6+/-24.4 n m) and Group III (102.7+/-15.9 n m). Among the patients with rheumatic heart disease, increasing nitrite level correlated significantly with worsening of contractile function [Nitrite v End systolic volume/Body surface area (T(xy.z)=0.23), Nitrite v End systolic dimension/Body surface area (T(xy.z)=0.32), Nitrite v left ventricular ejection fraction (T(xy.z)=-0.24), Nitrite v tricuspid annular plane systolic excursion (T(xy.z)=-0. 29)] and worsening New York Heart Association (NYHA) functional class (r(s)=0.5). We conclude that plasma nitrite, a stable end product of nitric oxide metabolism is increased in patients of rheumatic valvular heart disease with cardiac failure, suggesting increased nitric oxide production. Increased level of nitric oxide might be playing a significant role in myocardial contractile dysfunction and alteration of vascular response in cardiac failure.

Clinical, echocardiographic, and angiographic profile of patients with double-chambered right ventricle: experience with 48 cases.

Forty-eight patients with double-chambered right ventricle (DCRV) were prospectively studied over a 3-year period. Clinical, echocardiographic, hemodynamic, and angiographic studies were done in all. Three patients were studied postoperatively also. Fifteen patients underwent surgery confirming the diagnosis. Echocardiography detected anomalous muscle bundles (AMBs) in 39/41 patients in whom this study was carried out. Angiographically AMBs were best demonstrated in anteroposterior views in a systolic frame. Common associated anomalies found with DCRV were ventricular septal defects (69%), pulmonary valve stenosis (38%), and double-outlet right ventricle (10%).

Cyclin D3 expression, cell proliferation and pathological stage of human primary colorectal cancer.

Cyclin D3 promotes cell cycle progression but its expression and prognostic significance in human colorectal cancer is unknown. This study assayed cyclin D3 expression against cell cycle phase fraction and Duke's stage in 35 fresh human primary colorectal cancers. DNA content, cell cycle phase fraction and cyclin D3 expression were assessed by flow cytometry in disaggregated tumors. Cyclin D3 expression and S-phase fraction were independently related to Duke's stage. In Duke's stage C tumors, a higher proportion of cells expressed cyclin D3 (14.4 vs. 8.8%, mean; p < 0.05 by Mann-Whitney U test) and were in DNA synthesis (S) phase (21.1 vs. 9.7%, mean; p < 0.05 by Mann-Whitney U test). Neoplastic deregulation of cyclin D3 expression may provide a selective growth advantage which is related to stage in human colorectal cancer.

Colonic epithelial cell proliferation in hereditary non-polyposis colorectal cancer.

BACKGROUND: Despite the recent discovery of four genes responsible for up to 90% of all cases of hereditary non-polyposis colorectal cancer (HNPCC), there will still be families in whom predictive testing is not possible. A phenotypic biomarker would therefore be useful. An upwards shift of the proliferative compartment in colonic crypts is reported to be one of the earliest changes in premalignant mucosa. AIMS: To assess the role of crypt cell proliferation as a phenotypic biomarker in HNPCC. PATIENTS: Thirty five patients at 50% risk of carrying the HNPCC gene (21 of whom subsequently underwent predictive testing and hence gene carrier status was known) and 18 controls. METHODS: Crypt cell proliferation was measured at five sites in the colon using two different techniques. Labelling index was determined using the monoclonal antibody MIB1 and whole crypt mitotic index was measured using the microdissection and crypt squash technique. The distribution of proliferating cells within the crypts was also assessed. RESULTS: There were no significant differences in the total labelling index or mean number of mitoses per crypt, nor in the distribution of proliferating cells within the crypt, between the study and control groups at any site. When the 21 patients in whom gene carrier status was known were analysed separately there were no significant differences in the measured indices of proliferation between the HNPCC gene carriers and non-gene carriers. CONCLUSION: Crypt cell proliferation is not a discriminative marker of gene carriage in HNPCC.