Prospective multicenter observational trial on the safety and efficacy of LEVORAG® Emulgel in the treatment of acute and chronic anal fissure.

BACKGROUND: Anal fissure (AF) is a common cause of anal pain with a tendency not to heal spontaneously because of ischemia of the anoderm caused by sphincter spasm. Lateral internal sphincterotomy, while very effective, can cause fecal incontinence and chemical sphincterotomy by application of cream may have discouraging side effects and/or low efficacy. The aim of this prospective multicenter study was to evaluate the safety and effectiveness of a new medical treatment based on Emulgel cream, with emollient, soothing and protective agents, on AF healing. METHODS: Consecutive patients with AF treated in nine coloproctology units during 6 months entered the study on topical treatment with Levorag(®) Emulgel (THD S.p.A Correggio (RE), Italy). Before treatment, they had a proctologic examination and pain was measured using a visual analog scale. THD Levorag(®) Emulgel was applied every 12 h for 40 days. Monitoring was scheduled at 10, 20 and 40 days. At time 0 and at the end of treatment, patients underwent anorectal manometry, if possible. RESULTS: Two hundred eighty-four AF patients were recruited (171 acute fissures). Complete healing was achieved in 47.9 % of the cases, an improvement in 31.0 % (global efficacy 78.9 %). In patients with acute fissure, the rate of efficacy was 89.4 % (complete healing: 64.3 %, improvement: 25.1 %), in those with chronic fissure the rate of efficacy was 62.8 % (complete healing: 23 %, improvement: 39.8 %), p < 0.001. Pain and resting anal pressure decreased significantly after treatment. CONCLUSIONS: Treatment with THD Levorag(®) Emulgel proved to be effective for the reepithelization of AF and the reduction of pain in the short term in about 80 % of patients.

Local excision with adjuvant imatinib therapy for anorectal gastrointestinal stromal tumors.

Rectal gastrointestinal stromal tumors (GISTs) are uncommon, and the role of local excision versus a more extensive resection after the advent of effective targeted chemotherapy with imatinib is not known. Our aim is to present two cases of large anorectal GIST treated with local excision through a new anterolateral trans-sphincteric approach followed by adjuvant therapy with imatinib. Two patients (both males, 68 and 63 years old) presented at our institution with anorectal GIST in the period October-November 2010. Their medical records, pathology results, and imaging studies were retrospectively reviewed. Both patients presented with an anterior perianal mass. Imaging studies were characteristic of GIST originating in the lower rectum, circumscribed by a pseudocapsule, and protruding into the ischiorectal fossa. Both patients underwent local excision via an anterolateral trans-sphincteric approach. Both tumors were removed intact, with microscopically negative margins. The maximum tumor diameter was 8 and 9 cm, and the diagnosis of GIST was confirmed by positive CD117 and CD34 staining in both cases. Both tumors had a high (>5/50HPF) mitotic index. The patients had an uneventful postoperative course and were discharged on days 5 and 6. Both patients were started on imatinib 400 mg bid postoperatively. Postoperative magnetic resonance imaging and positron emission tomography computed tomography were carried out at 12 months and did not reveal any signs of recurrence. The patients are currently disease-free at 24 and 23 months of follow-up. In selected cases, complete excision of rectal GIST with negative margins is feasible via a trans-sphincteric approach. With the use of adjuvant therapy, which is currently advocated in all high-risk cases, it is possible that local excision with its reduced morbidity may become a viable alternative, especially in patients who would otherwise require abdominoperineal excision such as the two presented here. Prospective studies with longer follow-up are needed to confirm adequate oncologic results.

Emerging technologies in coloproctology: results of the Italian Society of Colorectal Surgery Logbook of Adverse Events.

BACKGROUND: The aim of this paper is to present the results of the Italian Society of Colorectal Surgery [or Società Italiana di Chirurgia Colorettale (SICCR)] Logbook of adverse events (AE) occurring in relation to emerging technologies in coloproctology (ETCs), over a 3-year period. METHODS: A total of 245 AE were reported (patients age: mean = 49.6 years, range = 20-75 years; gender: 155 = F, 90 = M). The "observations" originated from the same institution of the AEs in 44 cases (18.0%), while 201 patients (82.0%) had been operated on somewhere else. RESULTS: The three most reported ETCs were: Procedure for prolapsed haemorrhoids (PPH) (n = 120-48.9%), stapled transanal rectal resection (STARR (n = 96-39.2%), and transanal haemorrhoidal dearterialization (THD) (n = 11-4.5%). PPH, STARR, and THD together accounted for n = 227 (92.6%) observations. For the three main reported ETCs, the various AEs are listed. Chronic pain after PPH was 46/120 (38.3%), and after STARR of 21/96 (21.9%). The overall re-operation rate was n = 135 (55.1%) versus n = 110 (44.9%) no reoperation. In particular, for the three main reported ETCs, n = 68/120 (56.7%) following an AE after PPH, n = 47/94 (50.0%) following an AE after STARR, and n = 6/11 (54.5) following an AE post-THD. The various types of treatment to solve AE after each of the three most observed ETCs are reported in the text. CONCLUSIONS: Our results do not allow us to draw statistical conclusions; however, this was not the aim of our survey. ETCs are important, yet they are not without major risks. Manufacturers should help colorectal surgeons to convey the right message to patients.

Seton or glue for trans-sphincteric anal fistulae: a prospective randomized crossover clinical trial.

OBJECTIVE: Fibrin glue treatment of anal fistulae has been proposed to minimize the risk of faecal incontinence but its acceptance by coloproctologists is still poor because the published data is controversial. Therefore, we carried out a prospective randomized crossover trial comparing treatment with a commercial fibrin glue to classical seton treatment, with healing rate, hospital stay, healing time, faecal incontinence and postoperative pain as study outcomes. METHOD: Sixty-four homogeneous patients with trans-sphincteric anal fistulae referred to seven colorectal units were randomized to undergo fibrin glue (39 patients) or seton (25 patients) treatment. Patients failing to heal after treatment with fibrin glue were re-randomized to undergo a second injection with glue or seton treatment. RESULTS: Sixty-two of the 64 patients completed the minimum 1-year follow-up period. Twenty-one of 24 patients healed in the seton group compared with 15/38 in the fibrin glue group (P = 0.0007). The 23 failures after glue treatment were re-randomized to have a second glue injection (eight patients) or a seton treatment (15 patients). Four of the eight (50%) patients treated with a second injection of glue, and nine out of the 15 (60%) patients in the seton group, healed. Patients treated with fibrin glue reported less postoperative pain and had a shorter hospital stay than patients treated with a seton; furthermore, faecal continence and anal manometry significantly worsened after seton treatment. CONCLUSION: Seton treatment has a significantly higher probability of success compared with fibrin glue treatment but poses a higher risk of faecal incontinence. Fibrin glue could be considered as a first line of treatment for patients at risk of faecal incontinence or other comorbidities.

Optimal treatment duration of glyceryl trinitrate for chronic anal fissure: results of a prospective randomized multicenter trial.

BACKGROUND: Chronic anal fissure (CAF) is a painful condition that is unlikely to resolve with conventional conservative management. Previous studies have reported that topical treatment of CAF with glyceryl trinitrate (GTN) reduces pain and promotes healing, but optimal treatment duration is unknown. METHODS: To assess the effect of different treatment durations on CAF, we designed a prospective randomized trial comparing 40 versus 80 days with twice daily topical 0.4% GTN treatment (Rectogesic, Prostrakan Group). Chronicity was defined by the presence of both morphological (fibrosis, skin tag, exposed sphincter, hypertrophied anal papilla) and time criteria (symptoms present for more than 2 months or pain of less duration but similar episodes in the past). A gravity score (1 = no visible sphincter; 2 = visible sphincter; 3 = visible sphincter and fibrosis) was used at baseline. Fissure healing, the primary endpoint of the study, maximum pain at defecation measured with VAS and maximum anal resting pressure were assessed at baseline and at 14, 28, 40 and 80 days. Data was gathered at the end of the assigned treatment. RESULTS: Of 188 patients with chronic fissure, 96 were randomized to the 40-day group and 92 to the 80-day group. Patients were well matched for sex, age, VAS and fissure score. There were 34 (19%) patients who did not complete treatment, 18 (10%) because of side effects. Of 154 patients who completed treatment, 90 (58%) had their fissures healed and 105 (68%) were pain free. There was no difference in healing or symptoms between the 40- and the 80-day group. There was no predictor of fissure healing. A low fissure gravity score correlated with increased resolution of pain (P < 0.05) and improvement of VAS score (P < 0.05) on both univariate and multivariate analysis. A lower baseline resting pressure was associated with better pain resolution on univariate analysis (P < 0.01). VAS at defecation and fissure healing significantly improved until 40 days (P < 0.001), while the difference between 40 and 80 days was not significant. CONCLUSION: We found no benefits in treating CAF with topical GTN for 80 days compared to 40 days. Fissure healing and VAS improvement continue until 6 weeks of treatment but are unlikely thereafter.

Ligasure Precise vs. conventional diathermy for Milligan-Morgan hemorrhoidectomy: a prospective, randomized, multicenter trial.

PURPOSE: Milligan-Morgan hemorrhoidectomy using radiofrequency dissection (Ligasure) has been proposed instead of conventional diathermy in view of its potential benefits in terms of postoperative anal pain and better hemostatic control, but the medical literature is still controversial. This multicenter, randomized, controlled trial was designed to compare the outcomes between Ligasure and conventional diathermy hemorrhoidectomy in the Milligan-Morgan procedures in a sufficient number of patients. METHODS: Patients with Grades III and IV hemorrhoids were randomized to two groups: Ligasure hemorrhoidectomy and conventional diathermy. Postoperative anal pain was measured by the Visual Analog Scale (VAS) and the analgesia required. Postoperative complications, wound healing, and return to working activities also were evaluated as secondary outcomes. RESULTS: A total of 273 patients, well matched for age, gender, working activity and grade of hemorrhoids, were randomized to two groups: Ligasure 146, and diathermy 127. The severity of postoperative anal pain was significantly less in the Ligasure group when measured at least 12 hours after defecation (P < 0.01), whereas it was similar at the time of defecation. The Ligasure group had significantly lower requirements for painkiller pills. There were no significant differences in early and late complications. Return to work and normal activities was significantly faster in the Ligasure group. CONCLUSION: Ligasure hemorrhoidectomy is an effective procedure for Grades III and IV hemorrhoids and facilitates a faster return to work and normal activities by reducing postoperative pain.

A prospective evaluation of occult disorders in obstructed defecation using the 'iceberg diagram'.

OBJECTIVE: Surgical treatment of constipation and obstructed defecation (OD) carries frequent recurrences, as OD is an 'iceberg syndrome' characterized by 'underwater rocks' or occult diseases which may affect the outcome of surgery. The aim of this study was to evaluate occult disorders, in order to alert the clinician of these and minimize failures. METHOD: One hundred consecutive constipated patients with OD symptoms, 81 women, median age 52 years, underwent perineal examination, proctoscopy, anorectal manometry and anal/vaginal ultrasound (US). Anorectal physiology and imaging tests were also carried out when indicated, as well as psychological and urogynaecological consultations. Symptoms were graded using a modified 1-20 constipation score. Both evident (e.g. rectocele) and occult (e.g. anismus) diseases were prospectively evaluated using a novel 'iceberg diagram'. The type of treatment, whether conservative or surgical, was also recorded. RESULTS: Fifty-four (54%) patients had both mucosal prolapse and rectocele. All patients had at least two occult OD-related diseases, 66 patients had at least three of them: anxiety-depression, anismus and rectal hyposensation were the most frequent (66%, 44% and 33%, respectively). The median constipation score was 11 (range 2-20), the median number of 'occult disorders' was 5 (range 2-8). Conservative treatment was carried out in most cases. Surgery was carried out in 14 (14%) patients. CONCLUSION: The novel 'iceberg diagram' allowed the adequate evaluation of OD-related occult diseases and better selection of patients for treatment. Most were managed conservatively, and only a minority were treated by surgery.

Anal endosonography: a survey of equipment, technique and diagnostic criteria adopted in nine Italian centers.

BACKGROUND: Anal endosonography (AES) has become an essential part of the pre-operative diagnostic workup in both organic and functional anal diseases. METHODS: Nine Italian centres with an average volume activity of >10 exams/week each were surveyed with the aim of determining the concordance with respect to indications for the procedure and interpretation of the results. RESULTS: Overall, anal sepsis, faecal incontinence and anorectal tumours were the more common indications for AES while evacuation dysfunctions and anal pain were not always considered indications. All centres use the same diagnostic criteria for simple and complicated perirectal sepsis and sphincteric defects, but adopt different classifications for stage 1 and stage 2 anal tumours. Participants agreed in that lymph-node staging by AES is less precise than tumour staging, especially after chemoradiation therapy. CONCLUSIONS: A list of recommendations and guidelines based on the groups's experience has been produced for those radiologists and coloproctologists interested in the use of AES and accreditation of their centres.

A prospective evaluation of occult disorders in obstructed defecation using the 'iceberg diagram'.

OBJECTIVE: Surgical treatment of constipation and obstructed defecation (OD) carries frequent recurrences, as OD is an 'iceberg syndrome' characterized by 'underwater rocks' or occult diseases which may affect the outcome of surgery. The aim of this study was to evaluate occult disorders in order to alert the clinician of these and minimize failures. METHOD: One hundred consecutive constipated patients with OD symptoms, 81 female patients, median age 52 years, underwent perineal examination, proctoscopy, anorectal manometry, and anal/vaginal ultrasound. Anorectal physiology and imaging tests were also carried out when indicated, as well as psychological and urogynaecological consultation. Symptoms were graded using a modified 1-20 constipation score. Both evident (e.g. rectocele) and occult (e.g. anismus) diseases were prospectively evaluated using a novel 'iceberg diagram'. The type of treatment, whether conservative or surgical, was also recorded. RESULTS: Fifty-four (54%) patients had both mucosal prolapse and rectocele. All patients had at least two occult OD-related diseases, 66 patients had at least three: anxiety-depression, anismus and rectal hyposensation were the most frequent (66%, 44% and 33% respectively). The median constipation score was 11 (range 2-20), the median number of 'occult disorders' was 5 (range 2-8). Conservative treatment was carried out in most patients. Surgery was carried out in 14 (14%) patients. CONCLUSION: The novel 'iceberg diagram' allowed the adequate evaluation of OD-related occult diseases and better selection of patients for treatment. Most were managed conservatively, and only a minority were treated by surgery.

Which surgical approach for rectocele? A multicentric report from Italian coloproctologists.

The most effective surgical technique for rectocele has not yet been clearly established. A retrospective multicentric study was carried out to compare the long-term results of 3 endorectal techniques (Block, Sarles and stapled) and the perineal levatorplasty, alone and in association, in a series of patients with symptomatic rectocele. From January 1992 to December 1999, 2212 patients with defecation disorders were referred to 5 Italian coloproctology units. An anterior rectocele was clinically diagnosed in 1045 patients and confirmed with defecography. On the basis of clinical and radiological parameters, 317 patients (312 women; mean age, 52.4+/-20.1 years) were selected for surgery. Group 1 consisted of 141 patients (136 women; mean age, 50.4+/-18.8 years) who were submitted to endorectal operations. Group 2 consisted of 126 women (mean age, 52.5+/-19.7 years) who received perineal levatorplasty. Finally, 50 women (mean age, 54.3+/-21.9 years) in Group 3 received endorectal operations associated with perineal levatorplasty. A total of 269 patients were followed postoperatively (mean period, 24.2+/-3.1 months, 27.5+/-5.4 months and, 22.8+/-2.8 months, respectively) with the same questionnaire and clinical examination. Three months after surgery, a defecography examination and anorectal manometry were performed in 136 and 132 patients, respectively. Operative time, hospital stay and time to return to work were significantly higher in Group 3 (p<0.001). There was one death in Group 3 due to severe sepsis. Main postoperative complications were: in Group 1, hemorrhage (7.8%, all Sarles), dehiscence of the endorectal suture (5.0%, all Block), distal rectal stenosis (2.1%, 1 stapled, 2 block), and rectovaginal fistula (1.4%, all Sarles); in Group 2, delayed healing of the perineal wound (16.4%); in Group 3 delayed healing of the perineal wound (22.0%), hemorrhage (6%, all Sarles), dehiscence (4.0%), stenosis (2.0%). 17.3% of patients of Group 2 and 22.5% of Group 3 complained of dyspareunia. Postoperative defecography showed a complete absence of the rectocele in 44.1% of patients and reduction of size in the others, without significant differences among the three groups. Manometric pattern was not significantly modified by surgery. Significant symptoms recurred in 5.9% of the patients in Group 1, 6.4% in Group 2, and 5.0% in Group 3. Perineal levatorplasty did not significantly improve obstructed defecation, as it did not allow to excise the rectal mucosal prolapse, and was followed by an high incidence of delayed healing of the perineal wound and dyspareunia. Sarles procedure achieved better control of mucosal prolapse but carried a higher complication rate compared to the others. The association of the perineal levatorplasty with an endorectal technique required significantly longer operative time, and led to a longer hospital stay and time to return to work. In conclusion, the investigated techniques showed different patterns of postoperative complications: bleeding after Sarles, dehiscence after Block, dyspareunia after perineoplasty and fatal gangrene after stapled, but non of them showed a clear superiority over the others in term of clinical or functional results 2 years after surgery.

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.