Consensus statement of the Italian society of colorectal surgery (SICCR): management and treatment of hemorrhoidal disease.

Hemorrhoidal disease (HD) is the most common proctological disease in the Western countries. However, its real prevalence is underestimated due to the frequent self-medication.The aim of this consensus statement is to provide evidence-based data to allow an individualized and appropriate management and treatment of HD. The strategy used to search for evidence was based on application of electronic sources such as MEDLINE, PubMed, Cochrane Review Library, CINAHL, and EMBASE.These guidelines are inclusive and not prescriptive.The recommendations were defined and graded based on the current levels of evidence and in accordance with the criteria adopted by American College of Chest Physicians. The recommendations were graded A, B, and C.

Individual participant data pooled-analysis of risk factors for recurrence after neoadjuvant radiotherapy and transanal local excision of rectal cancer: the PARTTLE study.

BACKGROUND: An organ-preserving strategy may be a valid alternative in the treatment of selected patients with rectal cancer after neoadjuvant radiotherapy. Preoperative assessment of the risk for tumor recurrence is a key component of surgical planning. The aim of the present study was to increase the current knowledge on the risk factors for tumor recurrence. METHODS: The present study included individual participant data of published studies on rectal cancer surgery. The literature was reviewed according to according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data checklist (PRISMA-IPD) guidelines. Series of patients, whose data were collected prospectively, having neoadjuvant radiotherapy followed by transanal local excision for rectal cancer were reviewed. Three independent series of univariate/multivariate binary logistic regression models were estimated for the risk of local, systemic and overall recurrence, respectively. RESULTS: We identified 15 studies, and 7 centers provided individual data on 517 patients. The multivariate analysis showed higher local and overall recurrences for ypT3 stage (OR 4.79; 95% CI 2.25-10.16 and OR 6.43 95% CI 3.33-12.42), tumor size after radiotherapy > 10 mm (OR 5.86 95% CI 2.33-14.74 and OR 3.14 95% CI 1.68-5.87), and lack of combined chemotherapy (OR 3.68 95% CI 1.78-7.62 and OR 2.09 95% CI 1.10-3.97), while ypT3 was the only factor correlated with systemic recurrence (OR 5.93). The analysis of survival curves shows that the overall survival is associated with ypT and not with cT. CONCLUSIONS: Local excision should be offered with caution after neoadjuvant chemoradiotherapy to selected patients with rectal cancers, who achieved a good response to neoadjuvant chemoradiotherapy.

Practice parameters for the diagnosis and treatment of anal intraepithelial neoplasia (AIN) on behalf of the Italian Society of Colorectal Surgery (SICCR).

Squamous cell carcinoma (SCC) of the anus is a human papilloma virus (HPV) related malignancy that is preceded by anal intraepithelial neoplasia (AIN) making this cancer, at least theoretically, a preventable disease. In the past 10 years the diagnosis, management and nomenclature of AIN has dramatically changed. Increased life expectancy in human immunodeficiency virus (HIV) positive patients due to highly active antiretroviral therapy (HAART) has caused an increase in the incidence of SCC of the anus. While many experts recommend screening and treatment of anal high-grade squamous intraepithelial lesion (HSIL), there is no consensus on the optimal management these lesions. Therefore, there is a need to review the current evidence on diagnosis and treatment of AIN and formulate recommendations to guide management. Surgeons who are members of the Italian Society of Colorectal Surgery (SICCR) with a recognized interest in AIN were invited to contribute on various topics after a comprehensive literature search. Levels of evidence were classified using the Oxford Centre for Evidence-based Medicine of 2009 and the strength of recommendation was graded according to the United States (US) preventive services task force. These recommendations are among the few entirely dedicated only to the precursors of SCC of the anus and provide an evidence-based summary of the current knowledge about the management of AIN that will serve as a reference for clinicians involved in the treatment of patients at risk for anal cancer.

Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer.

PURPOSE: This study aimed at investigating whether the irradiated volume of pelvic bone marrow (PBM) and specific subsites may predict the occurrence of acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. METHODS: 50 patients, submitted to IMRT and concurrent chemotherapy, were analyzed. Several bony structures were defined on planning-CT: PBM and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb) and platelet nadirs and acute hematologic toxicity (HT) according to RTOG scoring scale. Generalized linear modeling was used to find correlations between dosimetric variables and blood cell nadirs, while logistic regression analysis was used to test correlation with ≥G3 HT. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the optimal cut-off points for predictive dosimetric variables with the Youden method. RESULTS: Maximum detected acute HT comprised 38 % of ≥G3 leukopenia and 32 % of ≥G3 neutropenia. Grade 2 anemia was observed in 4 % of patients and ≥G3 thrombocytopenia in 10 %. On multivariate analysis a higher PBM-V 20 was associated with lower WBC nadir. Increased LSBM-V 40 was correlated with a higher likelihood to develop ≥G3 HT. A cut-off point at 41 % for LSBM-V 40 was found. Patients with LSBM-V 40 ≥41 % were more likely to develop ≥G3 HT (55.3 vs. 32.4 %; p < 0.01). CONCLUSIONS: Increased low-dose to pelvic bony structures significantly predicted for WBC decrease. Medium-high dose to specific osseous subsites was associated with a higher probability of HT. LSBM-V 40 was a strong predictor of ≥G3 HT. A threshold at 41 % for LSBM-V 40 could be used to limit HT.

Perineal stapled prolapse resection for full-thickness external rectal prolapse: a multicentre prospective study.

AIM: Many different surgical techniques have been reported for the surgical treatment of full-thickness external rectal prolapse. Perianal stapled prolapse resection (PSP) is a relatively newly reported technique for full thickness external rectal prolapse. The aim of this prospective multicentre study was to evaluate the results of this procedure. METHOD: Consecutive patients who underwent a PSP resection for full-thickness external rectal prolapse at five centres were recruited to the study. Median operating time, hospital stay, complications, recurrence and functional results according to the Wexner Incontinence Scale and obstructive defaecation syndrome score were recorded. RESULTS: There were 27 patients treated by PSP. The median Wexner incontinence score improved from 10 presurgery to 5 after surgery (P < 0.001); the median obstructed defaecation syndrome score improved from 12 presurgery to 5 (range 4-10) after surgery (P < 0.001). A laparoscopically assisted procedure was performed in three patients (11.1%). The median number of cartridges used was six (range four to nine). The median operating time was 48 min. Early complications occurred in six patients (22.2%) and late complications in two (7.4%). The median length of hospital stay was 5 days. The recurrence rate at a median follow-up of 30.3 months was 14.8%. CONCLUSION: PSP appears to be an easy, fast and safe procedure. Early functional results are good. The recurrence rate compares favourably with other perineal procedures like the Delorme or the Altemeier operations. Long-term functional results need to be investigated further.

Evaluation and management of hemorrhoids: Italian society of colorectal surgery (SICCR) consensus statement.

Hemorrhoids are one of the most common medical and surgical diseases and the main reason for a visit to a coloproctologist. This consensus statement was drawn up by the Italian society of colorectal surgery in order to provide practice parameters for an accurate assessment of the disease and consequent appropriate treatment. The authors made a careful search in the main databases (MEDLINE, PubMed, Embase and Cochrane), and all results were classified on the basis of the grade of recommendation (A-C) of the American College of Chest Physicians.

Topical application of LEVORAG® as first-line treatment for chronic anal fissures: a preliminary multicentric study.

AIM: The aim of the present study was to assess the safety and efficacy of this new topical agent as a first line treatment in patients with chronic anal fissures. METHODS: Nine centres were involved in the study. Patients with chronic anal fissures were recruited and received Levorag® for 40 days. Follow-up visits were conducted at 10, 20 and 40 days from the recruitment. Primary outcome was the healing rate, secondary outcome the reduction of pain at the end of the treatment measured with a VAS scale. RESULTS: Fifty patients completed the treatment. No adverse events were recorded. 60% of patients healed completely at the end of the treatment. In those that did not heal the reduction of mean VAS values was 60%. CONCLUSION: The use of Levorag® on patients affected by chronic anal fissures achieved in the short term results similar to those experienced by more classic local treatments without any side effect.

Lymphogranuloma venereum: an old, forgotten re-emerging systemic disease.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection endemic in parts of Africa, Asia, South America, and the Caribbean, but once was rarely observed in Western countries, where most cases were considered to be imported. However, recent outbreaks have been reported in Europe, Australia, New Zealand, the United States and Canada, mainly among HIV positive men who have sex with men, signaling LGV re-emergence. The etiological agent of LGV is Chlamydia trachomatis serotypes L1, L2 and L3, and current outbreaks are mostly sustained by L2b type. The clinical course can be classically divided into three stages: an initial papule, which may ulcerate at the site of inoculation, followed by regional lymphoadenopathy (second stage, generally unilateral). In the tertiary stage, lymphatic obstruction, with elephantiasis of genitalia, and rectal involvement can lead to the formation of strictures and fistulae that may require surgical treatment. Recent cases are observed mainly among HIV positive people, often co-infected with HCV and others STIs, engaging in high-risk sexual practices. The main clinical picture is a relative new entity characterized by progressive ulcerative proctitis, the so called anorectal syndrome. Diagnosis is often delayed, requires a high index of clinical suspicion and must rely on the use of nucleic acid amplification tests. The differential diagnosis of proctitis should include LGV infection. Gastroenterologists, coloproctologists, dermatologists and other specialists need to be aware of LGV proctitis to avoid diagnostic delay and progression of disease to the tertiary stage.

A novel biomarker-based analysis reliably predicts nodal metastases in anal carcinoma: preliminary evidence of therapeutic impact.

AIM: Routine prophylactic inguinal irradiation in anal cancer may cause significant toxicity associated with overtreatment bias. The aim of this study was to determine the risk of regional node metastases in anal carcinoma by identifying predictive molecular biomarkers. METHOD: Clinicohistopathological data from 50 pretreatment anal carcinoma biopsies were collected. Immunohistochemical analyses with antibodies against Ki67, p53, epidermal growth factor receptor (EGFR) and YKL-40 were performed. Statistical correlations between biomarkers and clinicopathological features and outcomes were studied. Sentinel lymph node biopsy was performed in a subset of 36 patients. RESULTS: All patients had undergone synchronous radiochemotherapy; tumour recurrence had developed in 26%, and 16% had died. YKL-40 tumour expression correlated with lymph node metastasis, whereas no inguinal node metastases were found in any of the (14%) patients presenting with a YKL-40/EGFR-negative tumour. YKL-40 expression and node metastasis were both significantly associated with shorter overall and disease-free survival. Tumour grade significantly correlated with disease-free survival only. HIV, tumour histological type, Ki67, p53 and EGFR were not associated with outcome. CONCLUSION: YKL-40 expression in anal carcinoma is correlated with a poor outcome and can predict lymph node metastases. The combined absence of YKL-40 and EGFR expression in a first biopsy of anal carcinoma reliably selects a subset of patients without inguinal metastases. Such patients could be spared sentinel lymph node biopsy and/or inguinal radiotherapy.

The treatment of squamous anal carcinoma: guidelines of the Italian Society of Colo-Rectal Surgery.

The Italian society of colo-rectal surgery (SICCR) is dedicated to improving the study, prevention and management of the diseases of the colon, rectum and anus. One of the aims of the society is to establish guidelines to the treatment of these diseases. These guidelines are based on the international literature and on the best available evidence. Clinical practice guidelines are one of the most important instruments to provide therapeutic decision-making support, based on the best scientific evidence available at the time. Guidelines are advisory and not prescriptive, susceptible to continual variations secondary to innovations and new scientific evidence. These guidelines are a guide for all colo-rectal surgeons and physicians who approach anal cancer.

Long-term functional results and quality of life after transanal endoscopic microsurgery.

BACKGROUND: Of the few studies that have investigated quality-of-life (QoL) outcomes after transanal endoscopic microsurgery (TEM), the majority have reported only short-term follow-up data. This study assessed long-term clinical and instrumental outcomes (QoL, sexual, urinary and sphincter function) after TEM for extraperitoneal rectal cancer. METHODS: Preoperative and postoperative anorectal function was assessed in consecutive patients with benign rectal lesions or early rectal cancer, based on clinical scores and anorectal manometry. RESULTS: Between January 2000 and July 2005, 93 patients undergoing TEM completed the 60-month study protocol. The mean Wexner continence score increased from baseline at 3 months, began to decline within 12 months, and had returned to the preoperative value at 60 months. Urgency was reported by 65·0, 30·0 and 5 per cent of patients at 3, 12 and 60 months respectively (P < 0·050). A significant improvement was noted in various clinical and QoL scores at 12 and 60 months. Postoperative manometry values at 3 months were significantly lower than at baseline (P < 0·050), but had returned to preoperative values at 12 months. Tumour size of 4 cm or above was the only factor that significantly (P = 0·008) affected the rectal sensitivity threshold, the urge to defaecate threshold and the maximum tolerated volume at 3 months after TEM. CONCLUSION: TEM had no long-term effect on anorectal function or QoL. Lower anal resting pressure at early follow-up was not associated with defaecation problems in patients who were continent before surgery.

Immunostimulation to reduce recurrence after surgery for anal condyloma acuminata: a prospective randomized controlled trial.

AIM: Human papillomavirus is the most common cause of sexually transmitted disease. It is associated with immunosuppression and shows a marked tendency to recur. We investigated a natural immunostimulant aimed to reduce recurrence. METHOD: A randomized controlled study was carried out including 261 patients allocated to surgical excision alone (control group; n = 122) and surgical excision plus postoperative immunostimulation for 30 days with a natural product (STET; study group; n = 139). Patients with HIV positivity were excluded. All patients gave fully informed consent. RESULTS: The patients were followed for 6 months after surgery. Recurrence occurred in 7.2% (10/139) in the study group and in 27.1% (33/122) in the control group (P < 0.0001). There were no significant differences in the sex, sexual orientation, number of lesions, time to diagnosis and treatment or localization of lesions in the two groups. CONCLUSIONS: Immunostimulation using a natural product significantly reduced the incidence of recurrence of anal condylomata in patients undergoing surgical excision.

Extensive anal condylomatosis: prognosis in relation to viral and host factors.

OBJECTIVE: To evaluate the clinical course of extensive anal condylomatosis in relation to treatment modalities, patient comorbidity and immune function, and associated papillomavirus (HPV) sequences. METHOD: Clinical data, treatment modalities and follow-up were recorded and analysed in relation to host and viral type. Histology, immunohistochemistry and molecular analyses for HPV search and typing were performed on formalin-fixed paraffin-embedded samples. RESULTS: Sixteen patients [14 males, median age 41.8 years (range 19-66)] affected by extensive anal condylomatosis [10 Buschke-Lowenstein Tumors (BLT) and 6 condylomatosis] treated in three different Italian institutions were included. There was associated preoperative anal intraepithelial neoplasia grade 3 (AIN3) in one and invasive carcinoma in three patients. After radical resection (n = 16) recurrence occurred in 4/10 (40%) BLT patients. Malignancy before or after treatment developed in 5/16 (31.25%) patients. HPV sequences were present in all the samples of 15 evaluable patients (types 6 or 11, 9 patients; type 16, 6 patients). A statistically significant association was found between presence of HPV type 16 and both malignancy and recurrence. Viral variant L83V was present in 3/4 HPV 16 positive recurrent cases. CONCLUSION: Radical resection resulted in a favourable clinical course. Typing of HPV sequences in the management of patients affected by extensive anal condylomatosis may be useful.

[Treatment of functional diseases after rectum anal surgery: effectiveness of rehabilitation of the pelvic pavement]. / Trattamento dei disturbi funzionali dopo la chirurgia retto-anale: efficacia della riabilitazione del pavimento pelvico.

AIM: Anorectal dysfunction is routinely treated at the Center for Pelvic Floor Rehabilitation, San Giovanni University Hospital, Turin, Italy. Of a total of 147 patients treated between April 2007 and May 2008, 44 (30%) received pelvic floor rehabilitation following anorectal surgery. With this study we wanted to evaluate the response of patients with constipation and/or fecal incontinence to postsurgical pelvic floor rehabilitation designed to regain full or partial anorectal function and so improve their quality of life. MATERIAL AND METHODS: The study population was 44 patients, subdivided into 3 groups. One group (n=25) consisted of patients with fecal incontinence, which was further split into two subgroups: subgroup A (n=10) with direct involvement of the anal sphincter at surgery and subgroup B (n=15) without sphincter involvement. The second group (n=12) included patients with constipation. The third group (n=7) included patients with constipation and incontinence; this group was further split into 2 subgroups: those in which constipation (n=5) and those in which incontinence (n=2) was predominant. Pre- and postrehabilitation anorectal function was compared using two types of assessment: 1) clinical evaluation with the Wexner incontinence scale and 2) diagnostic evaluation with anorectal manometry in patients with fecal incontinence (plus transanal sonography to determine anatomic damage in the subgroups in which the sphincter had been involved) and defecography in those with constipation (plus transit radiography to exclude intestinal colic-associated constipation). RESULTS: The number of patients classified as having severe incontinence decreased from 8 to 1 (-87.5%), those with moderate incontinence decreased from 8 to 4 (-50%); 20 out of 25 patients presented with mild dysfunction at the end of the rehabilitation program. No difference in response to treatment was found between the two subgroups of patients with fecal incontinence nor among those with constipation. Of those with predominant constipation, none were classified as having severe dysfunction; the number of those with moderate dysfunction decreased from 13 to 7 (-54%). CONCLUSIONS: The study results show that, when sufficiently motivated, patients with fecal incontinence and constipation following anorectal surgery respond positively to pelvic floor rehabilitation.