Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial.

AIM: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF. METHOD: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis. RESULTS: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes. CONCLUSION: While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events.

Clinical and functional outcome of surgery for posttraumatic cloacal deformity.

AIM: Cloacal deformity is a disabling condition that severely affects a patient's quality of life. Surgery to repair cloacal deformity remains the mainstay of treatment. The aim of this study is to assess the clinical and functional outcome of patients treated for traumatic cloacal deformity by three different techniques. METHOD: A retrospective multicentre study was carried out using data from women operated on for cloacal deformity between 2015 and 2019. Demographic characteristics, the presence of urinary and/or faecal incontinence and manometric findings were collected. The main outcome measures were represented by St Mark's and Rockwood faecal incontinence quality of life scores. RESULTS: Thirty eight women with a median age of 34 years [interquartile range (IQR) 31-39 years] were enrolled. Perineoplasty was performed in 23 patients by direct suture of the rectovaginal septum, in five using the X-flap and in 10 by the Singapore flap. Median resting and squeezing pressures increased significantly from 28.15 (IQR 23-32.7) cmH2 O to 45 (IQR 31-60.7) cmH2 O (p = 0.0001) and from 47 (IQR 41.2-54.7) cmH2 O to 97.2 (IQR 80-118) cmH2 O (p = 0.0001), respectively. Maximum tolerable volume improved from 120 (IQR 90-137.5) ml to 137.5 (IQR 120-150) ml (p = 0.002). The St Mark's score decreased from 18 (IQR 14-20) to 4.5 (IQR 2-8) after 20 months (p = 0001). Sexual activity was confirmed by 16 patients preoperatively and by 27 postoperatively. A diverting stoma was performed in three patients after X-flap perineoplasty and in 14 treated by direct closure. No significant differences were found pre- and postoperatively between the three groups. CONCLUSION: Regardless of the technique used, surgical repair significantly improves both clinical and functional outcomes irrespective of the presence of a covering stoma.

Coloanal anastomosis or abdominoperineal resection for very low rectal cancer: what will benefit, the surgeon's pride or the patient's quality of life?

PURPOSES: Sphincter-saving operation with coloanal anastomosis (CAA) has become an established option for very low rectal cancer, but few studies have compared its functional results and quality of life (QoL) with abdominoperineal resection (APR) showing controversial results. PATIENTS AND METHODS: Patients treated for low rectal cancer with APR or CAA, disease-free after a median follow-up period of 26.5 (8-84) and 52.5 (12-156) months, respectively, were retrospectively reviewed. General and disease-specific changes in QoL and severity of disease were evaluated by Karnofsky scale, EORTC-C30, EORTC-CR38, SF-36, PGWBI, FIQL, PAC-QoL, ICIQ-SF, Stoma-QoL, AMS, Wexner's score and obstructed defecation syndrome (ODS) score. RESULTS: Twenty-six APR patients and 34 CAA patients entered the study. Karnofsky score did not show significant differences. The median Stoma-QoL was 58.2 (45-76.6), indicating a good stoma function in 95% of patients. EORTC-C30, CR38, PGWBI and SF-36 questionnaires did not show significant differences between the two groups except for sexual function (better after CAA, p = 0.01). Eleven patients after APR and eight after CAA had urinary incontinence, and its severity did not differ significantly. Eighteen of 21 CAA patients complained of faecal incontinence [AMS, 80 (15-120); Wexner, 13 (2-19)] with an impact on their QoL [FIQL: lifestyle, 1.75 (0-4); coping/behaviour, 1.3 (0-3.5); depression, 2.1 (0-5.2); embarrassment, 2 (0-4.6)] and 11 complained of obstructed defecation [7.5 (3-16)] with significant consequences on QoL [PAC-QoL, 30.4 (19.2-80.3)]. CONCLUSIONS: QoL in patients with permanent stoma and in those after CAA did not differ significantly. APR patients had worse sexual function, while most CAA patients had faecal incontinence and sometime obstructed defecation, with important impact on their QoL.

Functional outcome of sacral nerve stimulation in patients with severe constipation.

BACKGROUND: Sacral nerve stimulation has been reported as an effective treatment for constipation. OBJECTIVE: This study aimed to evaluate the therapeutic efficacy of permanent sacral nerve stimulation on the treatment of idiopathic constipation resistant to medical and behavioral management over a median follow-up period of 25.6 (range, 6-96) months. DESIGN: A retrospective review of a prospectively maintained institutional review board-approved database was performed. SETTING: The study was performed at 2 tertiary-care European institutions with expertise in sacral nerve stimulation. PATIENTS: Patients were considered eligible if they had had symptoms for at least 1 year and if conservative treatment had failed. INTERVENTION: Patients were tested by percutaneous nerve evaluation before the procedure. If this evaluation was successful, patients underwent sacral nerve therapy with an implanted device. MAIN OUTCOME MEASURE: Patients were evaluated by means of a bowel function diary and the Wexner constipation score. RESULTS: A total of 48 consecutive patients (39 females, median age 50.0 years (range, 17-79 years) entered the study. Twenty-three patients were implanted with a permanent stimulator. On an intention-to-treat basis, only 14 of 48 patients (29.2%) met the definition of a successful outcome at the latest follow-up period (median, 25.6 (range, 6-96) months). The mean Wexner score decreased from 20.2 (SD 3.6) at baseline to 5.8 (SD 4.1) at the latest follow-up examination (p < 0.001). However, 6 of 14 patients (42.8%) were still using laxatives and/or enemas at the last follow-up. LIMITATIONS: The study was limited by the pragmatic approach necessary to evaluate the results in routine clinical practice. CONCLUSIONS: This study shows that sacral nerve stimulation has limited efficacy on an intention-to-treat basis as a routinely recommended therapy for intractable idiopathic constipation.

Management and Treatment of External Hemorrhoidal Thrombosis.

Background: External hemorrhoidal thrombosis (EHT) is a common complication of hemorrhoidal disease. This condition causes extreme pain, likely resulting from internal anal sphincter hypertonicity, which traps the hemorrhoids below the dentate line thus leading to congestion and swelling. The choice of treatment remains controversial and both conservative and surgical options have been proposed in the last decades. Methods: This mini-review focuses on the most relevant studies found in literature evaluating conservative and surgical management of EHT. Special conditions such as pregnancy and EHT in elderly patients have been considered. Results: Traditionally, symptoms duration represents the discriminant in the choice between medical and surgical treatment. Several Coloproctological Societies considered conservative treatment as the first-line approach to EHT and a variety of options have been proposed: wait and see, mixture of flavonoids, mix of lidocaine and nifedipine, botulinum toxin injection and topical application of 0.2% glyceryl trinitrate. Meanwhile, different surgical treatments are recommended when EHT fails to respond to conservative management or when symptoms onset falls within the last 48-72 h: drainage with radial incision, conventional excision, excision under local anesthesia and stapled technique. Conclusion: The management and treatment of EHT is still controversial since no specific guidelines have been published. Both medical and surgical treatment have been proven effective but randomized clinical trials and structured consensus-based guidelines are warranted.

Safety and Effectiveness of Tailored Hemorrhoidectomy in Outpatients Setting.

Introduction: Single or double prolapsed pile instead of full muco-hemorrhoidal prolapse is a common finding in patients with symptomatic III or IV degree hemorrhoids. For this selected group of patients, relief of symptoms could be achieved by managing the single/double prolapsed piles instead of performing traditional hemorrhoidectomy. The aim of this single-center study was to evaluate the safety and medium- and long-term effectiveness of an outpatient tailored Milligan-Morgan hemorrhoidectomy (MMH) performed under local anesthesia (LA). Material and methods: Clinical records of 202 patients submitted to outpatient tailored MMH, under LA and without anal dilation, treated between 2013 and 2020, were retrospectively reviewed using a prospectively maintained database and completed by a telephone interview or outpatient consultation. Postoperative pain score, the need for painkillers, postoperative complications and symptoms recurrence, return to working activities, and patient grading assessment scale were recorded. Results: Thirty-five (17%) out of 202 patients recruited were lost to the follow-up. One hundred and fifty-two and 15 patients underwent a single and double pile hemorrhoidectomy, respectively. With regard to postoperative outcomes, visual analogue scale (VAS) decreased from a median value of 4 [interquartile range (IQR) 2-6] on the day of surgery to 1 (IQR 0-4) on the 10th postoperative day (p < 0.001). Sixty-one patients (37%) needed oral painkillers during the 1st week after surgery. There was no mortality or major postoperative complication. Bleeding requiring hospital readmission was reported in seven (4%) patients, and one patient underwent emergency surgery with no need for blood transfusion. No postoperative urinary retention, anal incontinence, or stricture occurred in the series. During the median follow-up of 39 (IQR 12-60) months, 26 patients (16%) reported symptoms of recurrence but only six underwent traditional MMH. Recovery to normal activity occurred within a median period of 6 days (IQR 3-10) and the Clinical Patient Grading Assessment Scale (CPGAS) at 1 year after surgery was reported to be a "good deal better." Conclusions: Tailored MMH performed under LA in an ambulatory setting can be considered a safe and effective technique with high compliance and satisfaction of patients.

Giant fecaloma in an adult with severe anal stricture caused by anal imperforation treated by proctocolectomy and ileostomy: report of a case.

Although fecalomas are relatively common in patients who are elderly, constipated, or who have spinal injuries, a giant fecaloma formation unresponsive to conservative treatment is a rare condition that sometimes requires surgery for complications. Herein we report a case of a long-lasting (46 years) giant fecaloma associated with severe anal stricture after surgery for anal atresia and resulting in severe malnutrition, bone structural changes, and severe impairment of quality of life. Eight months after treatment by total proctocolectomy and ileostomy, the patient was on a free diet and had gained more than 10 percent of his postoperative body weight; improvements were observed in the tone of the abdominal muscles and in his quality of life.

Pharmacological and toxicological evaluation of a new series of thymidylate synthase inhibitors as anticancer agents.

Thymidylate synthase (TS) is responsible for catalysing the de novo biosynthesis of doexythymidine monophosphate and is a target for many anticancer drugs. A series of thymidylate synthase inhibitors (TSIs), synthesised in our laboratory, were submitted to primary anticancer screening by the National Cancer Institute (NCI). Four compounds, 3,3-bis(4-methoxyphenyl)-1H, 3H-naphtho[1,8-cd]pyran-1-one (MR7), 6-chloro-3,3-bis(4-hydroxyphenyl)-1H,3H-naphtho[1,8-cd]pyran-1-one (MR21), 3,3-bis(3-fluoro-4-hydroxyphenyl)-1H,3H-naphtho[1,8-cd]pyran-1-one (MR35) and 6-bromo-3,3-bis(3-chloro-4-hydroxyphenyl)-1H,3H-naphtho[1,8-cd]pyran-1-one (MR36), passed the criteria and were automatically scheduled for evaluation against the full panel of 60 human tumour cell lines. In this study, the antiproliferative activity of the substances against SK-MEL-2 cells (from metastatic tissue) and SK-MEL-28 cells (from primary malignant melanoma cells) was investigated. Neutral Red uptake and the MTT test were performed to confirm the results of the NCI, and [3H]-thymidine incorporation was performed as a test of the proliferation rate. Our results indicated that compounds MR21 and MR36 were the most active agents and the [3H]-thymidine test was the best in predicting toxicity against melanoma cells.

Structure-based studies on species-specific inhibition of thymidylate synthase.

Thymidylate synthase (TS) is a well-recognized target for anticancer chemotherapy. Due to its key role in the sole de novo pathway for thymidylate synthesis and, hence, DNA synthesis, it is an essential enzyme in all life forms. As such, it has been recently recognized as a valuable new target against infectious diseases. There is also a pressing need for new antimicrobial agents that are able to target strains that are drug resistant toward currently used drugs. In this context, species specificity is of crucial importance to distinguish between the invading microorganism and the human host, yet thymidylate synthase is among the most highly conserved enzymes. We combine structure-based drug design with rapid synthetic techniques and mutagenesis, in an iterative fashion, to develop novel antifolates that are not derived from the substrate and cofactor, and to understand the molecular basis for the observed species specificity. The role of structural and computational studies in the discovery of nonanalog antifolate inhibitors of bacterial TS, naphthalein and dansyl derivatives, and in the understanding of their biological activity profile, are discussed.

Double jejunal intussusception in an adult with chronic subileus due to a giant lipoma: a case report.

We present a case of a 40-year-old male with a clinical history of intermittent intestinal occlusion, abdominal pain and moderate weight loss. Physical examination and laboratory tests were unremarkable. Diagnostic imaging including CT, MR and small-bowel barium X-rays provided evidence of a jejunal lesion of an unknown nature downstream of the ligament of Treitz. Only at surgery was it possible to identify a double intussusception due to a giant stalked polyp which the histological examination revealed to be a submucosal lipoma.

[Italian translation and prospective validation of fecal incontinence quality of life (FIQL) index]. / Traduzione e validazione prospettica della versione italiana del Fecal Incontinence Quality Of Life (FIQL) index.

The evaluation of any functional disease affecting quality of life requires a purpose-designed quality-of-life index for clinical trials as well as for evaluating the outcomes of treatments. The fecal incontinence quality of life index (FIQL) was developed at Minnesota University (USA) for patients with faecal incontinence but could not be used for Italian patients without appropriate cultural and linguistic adaptation. Therefore this index was translated into italian and prospectively validated on a new series of 73 incontinent patients and 8 healthy controls in order to provide Italian coloproctologists with a useful tool for clinical research. The italian version or the FIQL index met all the statistical criteria of reliability, reproducibility, specificity and convergency required and therefore can be used with confidence in clinical trials on such patients.

Lack of prognostic role of pre- and postoperative peritoneal cytology and cytokeratin PCR-expression on local recurrence after curative anterior resection for mid-low rectal cancer.

Local recurrence continues to be a major problem in rectal cancer. After cancer removal, detection of viable cancer cells could be useful to identify patients at risk for local recurrence. Thus, aim of the study was the detection of residual peritoneal cancer cells with a possible prognostic role for local recurrence. Twenty-nine patients were operated (R0) for low (extraperitoneal) rectal cancer, without neoadjuvant radiochemotherapy. Before and immediately after cancer removal, a peritoneal lavage was done to evaluate by RT-PCR the cytokeratin 20 mRNA on isolated cells and in order to detect cancer cells by the Thin-prep test. After a median follow-up of 39 months, 5 patients died (17%), one for non-cancer-related disease, two (7%) for local recurrence and peritoneal carcinosis, and two for distant metastases. Preoperative cytology with Thin-prep test was positive in 4 patients (14%), while postoperative peritoneal cytology was positive only in 1 patient, different from the previous. No patient developed local or distal recurrence and all were disease-free at the end of the follow-up. RT-PCR analysis was positive on the peritoneal lavage after cancer removal in 11 patients. One died for unrelated cause and no one developed local recurrences. Local recurrence occurred in only 1 of the 2 patients with positive RT-PCR analysis on the first lavage and negative on the second lavage. Our study demonstrates a not important prognostic role of Thin-prep test and RT-PCR of cytokeratin 20 mRNA on the detection of patients at risk for local recurrence after curative resection of rectal cancer.

Results, outcome predictors, and complications after stapled transanal rectal resection for obstructed defecation.

PURPOSE: Obstructed defecation may be treated by stapled transanal rectal resection, but different complications and recurrence rates have been reported. The present study was designed to evaluate stapled transanal rectal resection results, outcome predictive factors, and nature of complications. METHODS: Clinical and functional data of 123 patients were retrospectively analyzed. All patients had symptoms of obstructed defecation before surgery and had rectocele and/or intussusception. Of them, 85 were operated on by the authors and 38 were referred after stapled transanal rectal resection had been performed elsewhere. RESULTS: At a median follow-up of 17 (range, 3-44) months, 65 percent of the patients operated on by the authors had subjective improvement. Recurrent rectocele was present in 29 percent and recurrent intussusception was present in 28 percent of patients. At univariate analysis, results were worse in those with preoperative digitation (P<0.01), puborectalis dyssynergia (P<0.05), enterocele (P<0.05), larger size rectocele (P<0.05), lower bowel frequency (P<0.05), and sense of incomplete evacuation (P<0.05). Bleeding was the most common perioperative complication occurring in 12 percent of cases. Reoperations were needed in 16 patients (19 percent): 9 for recurrent disease. In the 38 patients referred after stapled transanal rectal resection, the most common problems were perineal pain (53 percent), constipation with recurrent rectocele and/or intussusception (50 percent), and incontinence (28 percent). Of these patients, 14 (37 percent) underwent reoperations: 7 for recurrence. Three patients presented with a rectovaginal fistula. One other patient died for necrotizing pelvic fasciitis. CONCLUSIONS: Stapled transanal rectal resection achieved acceptable results at the cost of a high reoperation rate. Patients with puborectalis dyssynergia and lower bowel frequency may do worse because surgery does not address the causes of their constipation. Patients with large rectoceles, enteroceles, digitation, and a sense of incomplete evacuation may have more advanced pelvic floor disease for which stapled transanal rectal resection, which simply removes redundant tissue, may not be adequate. This, together with the complications observed in patients referred after stapled transanal rectal resection, suggests that this procedure should be performed by colorectal surgeons and in carefully selected patients.

Long-term functional assessment of antegrade colonic enema for combined incontinence and constipation using a modified Marsh and Kiff technique.

PURPOSE: Constipation and fecal incontinence can severely affect quality of life for patients, particularly when simultaneously present. Malone antegrade colonic enema enables periodic colonic emptying, thus preventing uncontrolled passage of feces and constipation. METHODS: Eleven patients with fecal incontinence and severe constipation or perineal colostomy after Miles' operation underwent a modified Marsh and Kiff ileostomy for antegrade colonic enema. Before and after surgery, the patients were fully evaluated for gastrointestinal functions, including gallbladder and stomach emptying time, H(2)-breath test, colonic transit time, dynamic defecography, and anorectal manometry. The severity of incontinence and constipation was scored preoperatively and postoperatively by using the American Medical System score and Cleveland Clinic Constipation scale, respectively, whereas the quality of life was measured by the Gastrointestinal Quality of Life Index. The surgical technique involved division of the terminal ileum 10 to 15 cm from the ileocecal valve, anastomosis and intussusception of the ileum with the cecum, narrowing of the ileal conduit with a linear stapler, and a small, introflexed ileostomy with an advanced skin flap. RESULTS: During the postoperative period, the mean American Medical System score decreased significantly from 77 to 11 (P<0.01) and the mean Cleveland Clinic Constipation score from 23 to 8.5 (P<0.01) with a significant improvement of quality of life. Antegrade colonic enema did not affect gallbladder, gastric, or orocecal transit time, which remained comparable with baseline. Colonic scintigraphy showed that antegrade colonic enema was efficient to clean the whole colon and rectum, leaving only 24 (range, 6-40) percent of the initial radioactivity after 30 minutes. Ileal manometry confirmed the presence of a high-pressure zone, preventing accidental reflux. CONCLUSIONS: Modified Marsh and Kiff technique is a safe and effective surgical option to treat patients with combined fecal incontinence and severe constipation and those with perineal colostomy after Miles. It should be recommended as a last option before colostomy.

Red hot chili pepper and hemorrhoids: the explosion of a myth: results of a prospective, randomized, placebo-controlled, crossover trial.

PURPOSE: Spicy foods are appreciated by a large part of the world population but have been blamed for causing hemorrhoids or exacerbating their symptoms, although no epidemiologic studies have been performed supporting this hypothesis. In this double-blind, randomized, placebo-controlled, crossover trial, we have studied the effects of a single dose of red hot chili pepper on the hemorrhoidal symptoms. METHODS: Fifty patients with second-degree and third-degree symptomatic hemorrhoids were randomly assigned to take a capsule containing red hot chili powder or placebo during lunch, scoring five hemorrhoidal symptoms (bleeding, swelling, pain, itching, and burning) on a visual analog scale. After one week, crossover treatment was administered according to the same methodology. Other treatments and foods potentially related with anorectal symptoms were discontinued during the study periods. RESULTS: Patients assigned low scores to their hemorrhoidal symptoms before the study and the scores remained unchanged during the 48 hours after both placebo and chili pepper treatment, the latter showing no statistically significant effects. CONCLUSIONS: There is no scientific evidence that a spicy meal based on red hot chili pepper may worsen hemorrhoidal symptoms and, therefore, there is no reason to prevent these patients from occasionally enjoying a spicy dish if they so wish.

Combined perineal and endorectal repair of rectocele by circular stapler: a novel surgical technique.

PURPOSE: The aim of this study was to present a new technique for treatment of disabling rectocele when associated with internal mucosal prolapse or hemorrhoids using a 33-mm circular stapler. METHODS: Eight female patients complaining of obstructed defecation because of distention rectocele associated with internal mucosal prolapse or hemorrhoids and perineal descent entered the study. The rectovaginal septum was opened by diathermy up to the end of the rectal wall weakness. The perineal wound and the anus were held open by a self-retractor. Using a transparent anoscope (PPH 01 system), 2 mucosal pursestrings were prepared 5 and 8 to 9 cm distant from the dentate line. Posteriorly, only the submucosa was included in the pursestring; anteriorly, it included the rectal wall, which was kept separate from the vaginal wall. A transanal 33-mm circular stapler was then used to close the rectocele and treat the mucosal prolapse. Before closing the perineum a levatorplasty was fashioned. RESULTS: One patient had a vaginal tear during dissection of the septum, which healed spontaneously in one month. No other complications were recorded. Postoperative defecography showed correction of the rectocele and the posterior rectal prolapse in all patients. In two of them, a small lateral diverticulum could be seen, although this was asymptomatic. After a median follow-up of 12 months, all had significantly improved defecation (chronic constipation score dropped from 14.3 to 5, P < 0.04). CONCLUSION: Combined perineal and endorectal stapler repair of rectocele may be a useful new surgical tool for correcting distention rectocele associated with mucosal prolapse or hemorrhoids and perineal descent in selected patients. A longer follow-up on a larger number of patients is needed to confirm these preliminary results.

ortho-Halogen naphthaleins as specific inhibitors of Lactobacillus casei thymidylate synthase. Conformational properties and biological activity.

Thymidylate synthase (TS) (EC 2.1.1.45), an enzyme involved in the DNA synthesis of both prokaryotic and eukaryotic cells, is a potential target for the development of anticancer and antinfective agents. Recently, we described a series of phthalein and naphthalein derivatives as TS inhibitors. These compounds have structures unrelated to the folate (Non-Analogue Antifolate Inhibitors, NAAIs) and were selective for the bacterial versus the human TS (hTS). In particular, halogen-substituted molecules were the most interesting. In the present paper the halogen derivatives of variously substituted 3,3-bis(4-hydroxyphenyl)-1H,3H-naphtho[2,3-c]furan-1-one (1-5) and 3,3-bis(4-hydroxyphenyl)-1H,3H-naphtho[1,8-c,d]pyran-1-one (6-14) were synthesized to investigate the biological effect of halogen substitution on the inhibition and selectivity for the TS enzymes. Conformational properties of the naphthalein series were explored in order to highlight possible differences between molecules that show species-specific biological profile with respect to non species-specific ones. With this aim, the conformational properties of the synthesized compounds were investigated by NMR, in various solvents and at different temperatures, and by computational analysis. The apparent inhibition constants (K(i)) for Lactobacillus casei TS (LcTS) were found to range from 0.7 to 7.0 microM, with the exception of the weakly active iodo-derivatives (4, 10, 13); all] the compounds were poorly active against hTS. The di-halogenated compounds 7, 8, 14 showed the highest specificity towards LcTS, their specificity index (SI) ranging between 40 and >558. The di-halogenated 1,8-naphthalein derivatives (7-10) exhibited different conformational properties with respect to the tetra-haloderivatives. Though a clear explanation for the observed specificity by means of conformational analysis is difficult to find, some interesting conformational effects are discussed in the context of selective recognition of the compounds investigated by the LcTS enzyme.

Permanent sacral nerve modulation for fecal incontinence and associated urinary disturbances.

BACKGROUND AND AIMS: Sacral nerve modulation (SNM) using an implantable pulse generator is gaining increasing acceptance in the treatment of several functional disturbances of the urinary and intestinal tract. This new therapeutic approach offers new possibilities in the treatment of fecal incontinence (FI) by means of its possible effects on anorectal physiology. PATIENTS AND METHODS: Fourteen patients with FI, six of whom had associated urinary disturbances, underwent permanent SNM after successful peripheral nerve evaluation tests. All had a clinical evaluation including FI grading systems (American Medical systems, AMS; Continence Grading System, CGS) and quality of life questionnaires (Fecal Incontinence Quality of Life, FIQL), and anorectal physiology tests performed before and during electrostimulation. Two patients had a lead displacement which was repositioned. Median follow-up was 14 months (range 6-48 months). RESULTS: AMS scores decreased significantly from 101 to 67 after 24 months CGS scores from 15 to 2 after 2 months. The median number of episodes of major incontinence per 2 weeks decreased from 14 to 1 after 24 months. FIQL scores improved significantly in the nine patients tested from an overall score of 1.59 to 3.3, with improvement in all areas of the FIQL. Four of the six patients with associated urinary disturbances had a significant improvement in their symptoms. Anal resting and squeezing tone did not change significantly, nor did rectal volumetry, compliance, rectoanal inhibitory reflex, or length of the anal high-pressure zone, while 24-h rectal manometry showed inhibition of the spontaneous rectal motility complexes after meal and on awakening in the only two patients undergoing this investigation. CONCLUSION: Although the mechanism of action of SMN is still unclear and requires further investigations, clinical results are very encouraging, confirming the role of this new and safe procedure in the treatment of FI and associated urinary disturbances.