Safe ablation of the anal mucosa and perianal skin in rats using Photodynamic Therapy--a promising approach for treating Anal Intraepithelial Neoplasia.

BACKGROUND: Anal Intraepithelial Neoplasia (AIN), a pre-cursor of anal squamous carcinoma, is increasingly detected in individuals with impaired immune function. However, choices for effective, low morbidity treatment are limited. Photodynamic Therapy (PDT) is promising as it is known to ablate more proximal gastrointestinal mucosa with safe healing, without damage to underlying muscle. It can also ablate skin with safe healing and minimal scarring. METHODS: Pharmacokinetics: Normal rats were sensitised with 200mg/kg 5-aminolaevulinic acid (ALA) and killed 1-8h later. Anal tissues were examined by fluorescence microscopy to quantify the concentration of PPIX (protoporphyrin IX, the active derivative of ALA) in anal mucosa and in the underlying sphincter. PDT: Normal rats were sensitised similarly 3h later, laser light (635 nm) was delivered. Anal canal: 50-150 J/cm using 1cm diffuser fibre; for peri-anal skin, 50-200 J/cm(2), using microlens fibre. In each group, 2 rats were killed 3, 7, 14 and 28 days later and the anal region removed for histological examination. RESULTS: Pharmacokinetics: Peak concentration of PPIX in mucosa was at 3h, peak ratio mucosa: muscle, 6, seen at same time. PDT. Anal canal 50 J/cm: complete mucosal ablation by 3 days, complete regeneration by 28 days. Higher energies caused muscle damage with scarring. Peri-anal skin: 200 J/cm(2); complete ablation of skin, including appendages, complete healing by 28 days. Minimal effect with lower energy. CONCLUSION: ALA-PDT can ablate anal mucosa and peri-anal skin with safe healing and no underlying damage. However, over treatment can damage the sphincters. This technique is ready to undergo clinical trials.

Gastrointestinal manifestations of chronic granulomatous disease.

OBJECTIVE: Chronic granulomatous disease is a rare clinical entity characterized by recurrent infective and inflammatory complications. Patients are usually assigned to specialist centres, but nonspecialist clinicians may be required to treat these patients in the emergency setting. This review serves as a management guide to those clinicians who are faced with patients presenting with gastrointestinal manifestations of chronic granulomatous disease. METHODS: This review is based on a literature search (Medline and NLM PubMed) with manual cross-referencing of all articles related to gastrointestinal chronic granulomatous disease. RESULTS: Gastrointestinal tract involvement is present in most affected patients. Clinical presentation can mimic common surgical complications such as colitis, perianal sepsis, gastric outlet obstruction and liver abscess. A history of recurrent infections during childhood is common. Management involves haematological, microbiological, endoscopic and radiological investigations. Treatment modalities include early aggressive empirical antimicrobial therapy for sepsis, immunomodulation for inflammatory complications and surgical drainage of abscesses. CONCLUSION: Early involvement of a centre with immunological expertise combined with aggressive management of complications significantly improves morbidity and mortality from this rare condition.

Improving the morbidity of anorectal injury from pelvic radiotherapy.

OBJECTIVE: Radiation anorectal injury due to pelvic radiotherapy for non intestinal cancer is a significant cause of morbidity which may limit the treatment dose required. Conservative treatment options are of limited value and surgery is reserved only for the most severe complications. This review addresses radioprotection of the anorectum and aims to increase awareness amongst surgeons of the strategies that have been in practice in order to minimize the side-effects of radiotherapy while preserving its therapeutic efficacy. METHODS: This review is based on a literature search (Medline and NLM PubMed) with manual cross-referencing of all articles related to anorectal radiation injury. RESULTS: Optimization of radiation dose, the use of radioprotective agents and improvement in radiation delivery are the main areas of development. There are few data on the potential of altered fractionation schedules in reducing anorectal injury. A few phase I and II studies suggest that the pharmacological agents amifostine and misoprostol could be beneficial in limiting radiation damage but larger phase III studies are awaited. CONCLUSION: The introduction of 3-dimensional conformal radiation therapy and intensity modulated radiation therapy has been the most significant advance in reducing radiation morbidity.

Anal intraepithelial neoplasia.

BACKGROUND: Anal intraepithelial neoplasia (AIN) is believed to be a precursor of anal squamous cell cancer and its incidence is rising in high-risk groups, particularly those infected with the human immunodeficiency virus (HIV). The natural history of AIN is unclear and management strategies are lacking. METHODS: This review is based on a literature search (Medline and PubMed) with manual cross-referencing of all articles related to AIN. RESULTS AND CONCLUSIONS: The aetiology of AIN is intricately linked with human papilloma viruses. The pathological processes involved in the progression of AIN are becoming clearer but the natural history, particularly the rate of progression to invasive cancer, remains unknown. There is no standard management for AIN and this is mainly due to difficulties in both diagnosis and treatment. A variety of treatment options have been tried with varying success. Surgery is associated with significant recurrence, particularly in HIV-positive patients. Non surgical approaches with imiquimod, photodynamic therapy and vaccination are appealing, and further work is required. Long-term follow-up of these patients is essential until the natural history of AIN becomes clearer.

Obstructed defecation after undiverted ileoanal pouch reconstruction for ulcerative colitis: pharmacologic approach. Report of a case.

PURPOSE: Obstructed defecation after ileal pouch construction has been reported only after closure of the diverting loop ileostomy, and biofeedback was an effective treatment modality. METHOD: This is a case report of a patient with immediate obstructed defecation after ileal pouch-anal anastomosis without a covering loop ileostomy and its successful pharmacologic management. RESULTS: A 38-year-old female underwent restorative proctectomy and stapled ileal J-pouch-anal anastomosis without a covering loop ileostomy. On the seventh postoperative day, her pouch catheter (in lieu of a covering loop ileostomy) was removed and she failed to evacuate. After ruling out any technical complications, diltiazem was commenced with successful spontaneous pouch emptying. Obstructed defecation reoccurred after cessation of diltiazem one week later, but the symptoms resolved once the diltiazem was recommenced. CONCLUSIONS: Obstructed defecation has been reported in patients after pelvic pouch reconstruction. However, in all those patients a diverting loop ileostomy had been raised and their obstructive symptoms were only apparent after closure of the ileostomy and when the pouch had healed. The concern regarding our patient was the complete outlet obstruction so soon after surgery, with undue strain on the anastomosis and the potential risk of disruption. Our only two options were either to create a diverting loop ileostomy or to try a fast-acting pharmacologic agent (diltiazem) to treat the presumed levator spasm. The latter option spared the patient a further operation.

Insertion of self-expanding metal stents for malignant dysphagia: assessment of a simple endoscopic method.

AIM: To assess the efficacy, safety and long-term results of self-expanding metallic prostheses, placed using an entirely endoscopic method, for the relief of dysphagia in oesophageal carcinoma. PATIENTS AND METHODS: A consecutive series of 50 patients (30 men, 20 women), aged 43-91 years (median, 75 years) underwent stent placement (Ultraflex Stent, Boston Scientific, Watertown, MA, USA) under general anaesthesia without fluoroscopic control. RESULTS: Stent placement was successful in all patients. Swallowing improved from dysphagia score 4, 3 or 2 to score 1 (or 0) in all patients available for long-term follow-up (excluding two patients who died, and two who had resection, in the immediate post-stenting period). There were two early deaths that were, or could have been, procedure-related and one early complication, in addition to technical problems in 6 cases, all early in the series. Seven patients required endoscopic laser treatment, on 13 occasions, subsequently for tumour in-growth or over-growth. Of the 46 patients with long-term stents in situ, 36 patients died with a median survival time of 4 months (range 10 days to 24 months). At the time of writing, 10 patients are still alive with a median survival of 4 months (range 1-11 months). CONCLUSIONS: Self-expanding metallic stents provide rapid, safe and effective relief of dysphagia. They can provide long-term palliation (> 1 year) with endoscopic laser treatment for recurrent in-growing/over-growing tumour. Fluoroscopic control is not necessary for the safe and accurate placement of such stents.

Necrotising fasciitis in a HIV positive male: an unusual indication for abdomino-perineal resection.

We report a case of necrotising fasciitis of the genitoperineum (Fournier's gangrene) in a HIV positive male following incision and drainage of bilateral ischiorectal fossa abscesses. During surgery to debride the necrotic tissue the rectum was found to be perforated necessitating laparotomy and subsequent abdomino-perineal resection. Although previous reports of Fournier's gangrene in the HIV positive population exist, rectal involvement requiring excision has not previously been reported.

Anal endosonography in patients with anorectal symptoms after haemorrhoidectomy.

BACKGROUND: Anorectal symptoms after haemorrhoidectomy are common and treatment is often empirical. Because of this, an audit was carried out of the value of anal endosonography in patients with anorectal symptoms after haemorrhoidectomy. METHODS: Between May 1993 and February 1997, 16 patients (ten men and six women of median age 56 (range 35-77) years) were investigated by anal endosonography for anorectal symptoms after haemorrhoidectomy which involved anorectal incontinence (n = 10), anal pain (n = 4) and obstructive defaecation (n = 2). The findings were compared with those in a matched group of asymptomatic patients after haemorroidectomy. RESULTS: Anal endosonography demonstrated an abnormality in 12 symptomatic patients. Of the ten patients with anorectal incontinence, endosonography showed an internal anal sphincter defect (n = 5), a combined sphincter defect (n = 2) and an isolated external anal sphincter defect (n = 1). Normal appearances were seen in all asymptomatic patients. The endosonographic abnormalities of the four patients with anal pain included internal anal sphincter defect (n = 1), extrinsic mass (n = 1), and intersphincteric abscess (n = 1). One of the two patients with obstructive defaecation had an isolated external anal sphincter defect on endosonography. CONCLUSION: These results show a high yield of endosonographic abnormalities in patients who experience symptoms after haemorrhoidectomy. In particular, occult sphincter injury as a cause of incontinence in these patients can frequently be demonstrated.