Redo IPAA for long rectal cuff syndrome after ileoanal pouch for inflammatory bowel disease.

ABTRACT: BACKGROUND: When constructing an ileal pouch-anal anastomosis (IPAA), the rectal cuff should ideally be 1-2 cm long to avoid subsequent complications. METHODS: We identified patients from our IBD center who underwent redo IPAA for a long rectal cuff. Long rectal cuff syndrome (LRCS) was defined as a symptomatic rectal cuff ≥ 4 cm. RESULTS: Forty patients met the inclusion criteria: 42.5% female, median age at redo surgery 42.5 years. The presentation was ulcerative proctitis in 77.5% of the cases and outlet obstruction in 22.5%. The index pouch was laparoscopically performed in 18 patients (45%). The median rectal cuff length was 6 cm. The pouch was repaired in 16 (40%) cases, whereas 24 (60%) required the creation of a neo-pouch. At the final pathology, the rectal cuff showed chronic active colitis in 38 (90%) cases. After a median follow-up of 34.5 (IQR 12-109) months, pouch failure occurred in 9 (22.5%) cases. The pouch survival rate was 78% at 3 years. Data on the quality of life were available for 11 (27.5%) patients at a median of 75 months after redo surgery. The median QoL score (0-1) was 0.7 (0.4-0.9). CONCLUSION: LRCS, a potentially avoidable complication, presents uniformly with symptoms of ulcerative proctitis or stricture. Redo IPAA was restorative for the majority.

Proctitis in patients with monkeypox infection: a single-center analysis of 42 consecutive cases from a multidisciplinary observational study on monkeypox proctitis.

BACKGROUND: The current monkeypox (MP) virus outbreak was declared an international emergency in July 2022. The aim of this report is to describe our initial experience with patients with MP, focusing on proctitis. METHODS: We conducted an observational study between 20 May and 31 July 2022, on patients with MP at a reference tertiary center in Madrid, Spain. A descriptive analysis on MP was performed, focusing on its characteristics, symptoms, diagnosis, and outcomes. RESULTS: A total of 143 positive MP cases were diagnosed in our center; 42 of them [all male, median age 39 years (range: 22-57 years)] had proctitis (29.37%), and 3 patients (2.09%/MP total cases and 7.14%/MP proctitis) required surgical drainage of a perianal abscess. CONCLUSIONS: General and digestive surgeons must be aware of the presence of proctological impairment and complications due to MP virus.

Inflammation of the rectal remnant endangers the outcome of ileal pouch-anal anastomosis: a case-control study.

BACKGROUND: Inflammation of the rectal remnant may affect the postoperative outcome of ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). We aimed to determine the extent of inflammation in the anastomotic area during IPAA and to investigate the impact of proctitis on postoperative complications and long-term outcomes. METHODS: Three hundred thirty-four UC patients with primary IPAA were included in this retrospective case-control study. The histopathologic degree of inflammation in the anastomotic area was graded into three stages of no proctitis ("NOP"), mild to medium proctitis ("MIP"), and severe proctitis ("SEP"). Preoperative risk factors, 30-day morbidity, and follow-up data were assessed. Kaplan-Meier analysis was performed in the event of pouch failure. RESULTS: The prevalence of proctitis was high (MIP 40.4%, and SEP 42.8%). During follow-up, the incidence of complications was highest among SEP: resulting in re-intervention (n = 40; 28.2%, p = 0.017), pouchitis (n = 36; 25.2%, p < 0.01), and pouch failure (n = 32; 22.4%, p = 0.032). The time interval to pouch failure was 5.0 (4.0-6.9) years among NOP, and 1.2 (0.5-2.3) years in SEP (p = 0.036). ASA 3, pouchitis, and pouch fistula were independent risk factors for pouch failure. CONCLUSION: Proctitis at the time of IPAA is common. A high degree of inflammation is associated with poor long-term outcomes, an effect that declines over time. In addition, a higher degree of proctitis leads to earlier pouch failure.

[A case of ischemic proctitis caused by impaired venous blood flow 11 months after surgery for sigmoid colon cancer].

A Japanese male in his 50s was presented to our hospital with the chief complaint of positive fecal immunochemical test. He had a history of hypertension. He underwent colonoscopy and was diagnosed with sigmoid colon cancer. He also underwent laparoscopic sigmoid colectomy with D3 lymph node dissection for sigmoid colon cancer. The inferior mesenteric artery and inferior mesenteric vein were amputated at the root of the vessels. The patient received adjuvant chemotherapy and was recurrence-free. Eleven months after the surgery, lower abdominal pain during defecation appeared. Contrast-enhanced computed tomography (CT) and colonoscopy showed marked rectal mucosal edema and increased fatty tissue density (dirty fat sign) around the anorectal side of the anastomosis. Intestinal blood flow was maintained. There were many fine blood vessels around the rectal wall, and the amputated distal part of the superior rectal artery was retrogradely contrasted. Amputated superior rectal artery and superior rectal vein were dilated than before. Colonoscopy revealed mucosal redness, edema, and easy bleeding on the anorectal side of the anastomosis. Abdominal contrast-enhanced 3D-CT showed increased arterial blood flow and increased fine blood vessels around the rectal wall. It suggested the presence of an arteriovenous fistula and venous congestion. Conservative treatment with total parenteral nutrition and prednisolone infusion did not improve the patient's condition, and a colostomy was performed. After colostomy, the pain improved, and the CT scan of the abdomen showed improvement in arterial blood flow and venous congestion. Colostomy was closed after 10 months. There has been no relapse since the closure of the colostomy. There are few reports on ischemic proctitis on the anorectal side of the anastomosis after colon cancer resection due to impaired venous blood flow.

Diverting colostomy is an effective procedure for ulcerative chronic radiation proctitis patients after pelvic malignancy radiation.

BACKGROUND: Chronic radiation proctitis (CRP) with rectal ulcer is a common complication after pelvic malignancy radiation, and gradually deteriorating ulcers will result in severe complications such as fistula. The aim of this study was to evaluate effect of colostomy on ulcerative CRP and to identify associated influence factors with effectiveness of colostomy. METHODS: Between November 2011 to February 2019, 811 hospitalized patients were diagnosed with radiation-induced enteritis (RE) in Sun Yat-sen University Sixth Affiliated Hospital, among which 284 patients presented with rectal ulcer, and 61 ulcerative CRP patients were retrospectively collected and analyzed. RESULTS: The overall effective rate of colostomy on ulcerative CRP was 49.2%, with a highest effective rate of 88.2% within 12 to 24 months after colostomy. 9 (31.1%) CRP patients with ulcers were cured after colostomy and 12 (19.67%) patients restored intestinal continuity, among which including 2 (3.3%) patients ever with rectovaginal fistula. 100% (55/55) patients with rectal bleeding and 91.4% (32/35) patients with anal pain were remarkably alleviated. Additionally, multivariable analysis showed the duration of stoma [OR 1.211, 95% CI (1.060-1.382), P = 0.005] and albumin (ALB) level post-colostomy [OR 1.437, 95% CI (1.102-1.875), P = 0.007] were two independent influence factors for the effectiveness of colostomy on the rectal ulcer of CRP patients. CONCLUSIONS: Colostomy was an effective and safe procedure for treating rectal ulcer of CRP patients, and also a potential strategy for preventing and treating fistula. Duration of stoma for 12-24 months and higher ALB level could significantly improve the effectiveness of colostomy on ulcerative CRP patients.

Recommendations of the Crohn's Disease and Ulcerative Colitis Spanish Working Group (GETECCU) for the treatment of perianal fistulas of Crohn's disease. / Recomendaciones del Grupo Español de Trabajo de Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) para el tratamiento de las fístulas perianales de la enfermedad de Crohn.

Recommendations are advice that is given and considered to be beneficial; however, they are still suggestions and are therefore open to different interpretations. In this sense, the final objective of the review has been to try to homogenize, with the evidence available, the approach to the diagnosis and medical/surgical treatment of one of the most complex manifestations of Crohn's disease, such as simple and complex perianal fistulas.

Efficacy and safety of radiofrequency ablation for treatment of chronic radiation proctitis: A systematic review and meta-analysis.

BACKGROUND AND AIM: Although argon plasma coagulation is the current standard endoscopic treatment for chronic radiation proctitis (CRP), radiofrequency ablation (RFA) has emerged as an attractive alternative. The aim of this study is to evaluate the efficacy and safety of RFA for the treatment of CRP. METHODS: Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed from 2004 through March 2018. Review and data abstraction were performed independently by two authors. Measured outcomes included hemoglobin, transfusion dependence, number of treatment sessions, RFA settings, and serious adverse events. RESULTS: Six studies (n = 71; mean age 73.41 ± 1.88 years; 90.14% male) were included. Thirty-eight percent of patients failed prior treatment with argon plasma coagulation. Patients underwent a mean of 1.71 ± 0.34 RFA sessions with 24.54 ± 16.47 RFA applications per session. Pooled clinical and endoscopic success of RFA was 99% (95% confidence interval [CI]: 90-100; P < 0.001) and 100% (95% CI: 94-100; P < 0.001), respectively. Serious adverse events were reported in one patient-pooled rate of 0% (95% CI: 0-3; P < 0.001). Mean pre-procedure hemoglobin was 10.38 ± 1.82 g/dL with significant improvement observed post-RFA [weighted mean difference 2.49 g/dL (95% CI: 2.16-2.82; P < 0.001)]. Among transfusion-dependent patients, 85% (95% CI: 68-97; P < 0.001) became transfusion-free post-RFA. Pooled mean follow-up was 19.73 ± 9.72 months. CONCLUSION: Despite limited long-term data on RFA for CRP, available evidence suggests RFA is an effective and safe treatment.

Endoscopic diode laser therapy for chronic radiation proctitis.

The purpose of this study is to determine the effectiveness of endoscopic diode laser therapy in patients presenting rectal bleeding due to chronic radiation proctitis (CRP). A retrospective analysis of CRP patients who underwent diode laser therapy in a single institution between 2010 and 2016 was carried out. The patients were treated by non-contact fibers without sedation in an outpatient setting. Fourteen patients (median age 77, range 73-87 years) diagnosed with CRP who had undergone high-dose radiotherapy for prostatic cancer and who presented with rectal bleeding were included. Six required blood transfusions. Antiplatelet (three patients) and anticoagulant (two patients) therapy was not suspended during the treatments. The patients underwent a median of two sessions; overall, a mean of 1684 J of laser energy per session was used. Bleeding was resolved in 10/14 (71%) patients, and other two patients showed improvement (93%). Only one patient, who did not complete the treatment, required blood transfusions after laser therapy; no complications were noted during or after the procedures. Study findings demonstrated that endoscopic non-contact diode laser treatment is safe and effective in CRP patients, even in those receiving antiplatelet and/or anticoagulant therapy.

The surgical management of radiation proctopathy.

BACKGROUND: There is sparse evidence guiding the optimum surgical management of patients with radiation proctopathy (RP). The purpose of this review is to analyse all the literature on the surgical management of RP in order to guide physicians and surgeons as to when and what surgery should be employed for these patients. METHODS: A literature search of PubMed, EMBASE, MEDLINE, Ovid, and Cochrane Library using the MeSH terms "radiation proctopathy", "proctitis", "surgical management", and related terms as keywords was performed. The review included all articles that reported on the surgical management of patients with radiation proctopathy. All relevant articles were cross-referenced for further articles and any unavailable online were retrieved from hard-copy archive libraries. Eighteen studies including one prospective cohort study, fifteen retrospective cohort studies, and three small case series are included. CONCLUSION: Surgery is indicated for patients with RP for rectal obstruction, perforation, fistulae, or a failure of medical measures to control the symptoms of RP. Surgery centres mainly on diversion version resection. Diversion alone does not remove the damaged tissue leaving the patient at risk of continued complications including bleeding, perforation, occlusion, and abscess formation; however, major resectional surgery carries higher risks. Morbidity and mortality vary 0-44% and 0-11% for diversion only versus 0-100% and 0-14% for resectional surgery. There is no universally agreed surgical first-line approach. The data supports both resection with defunctioning stoma or diversion only as reasonable first-line surgical options for patients requiring surgery for RP.

Efficacy and safety of argon plasma coagulation in the management of extensive chronic radiation proctitis after pelvic radiotherapy for cervical carcinoma.

INTRODUCTION: Chronic radiation proctitis (CRP) usually develops 90 days or more after radiation. Currently, there is no standard available for the treatment of CRP. In argon plasma coagulation, monopolar diathermy is used to ionise the argon gas which coagulates the telengiectatic vessels in a noncontact fashion. However, there are very few studies which have reported its use in extensive CRP. We report the efficacy and safety of APC in seven patients with recurrent, extensive grade 3 radiation proctitis. MATERIALS AND METHODS: This is a retrospective analysis of patients treated with argon plasma coagulation in our institute from June 2013 to June 2016. After adequate bowel preparation, patients underwent APC at an average power of 50 W with flow rate of 5 L/min. All the visible telangiectasia was ablated which required many sittings. RESULTS: The median RPSAS symptom score for frequency of bleeding at enrolment was 5 (range 3-5). After completion of APC, the median RPSAS symptom score for frequency of bleeding decreased to 1. The median RPSAS symptom score for severity of bleeding was 5 (range 3-5). After completion of APC, the mean RPSAS symptom score for severity of bleeding decreased to 1. Mean haemoglobin level before treatment was 5.43 g/dl (SD 2.37). Mean haemoglobin level after treatment was10.04 g/dl (SD 2.0). Compared with pre-treatment levels after APC, there was a mean increase in haemoglobin of 4.61 + 1.78 [95% CI 2.97-6.25, p = 0.00]. CONCLUSION: Argon plasma coagulation is a safe, well tolerated and effective treatment option in extensive chronic radiation proctitis which is refractory to medical management.

Current status of trans-anal total mesorectal excision (TaTME) following the Second International Consensus Conference.

This article documents the consensus of an expert group of surgeons from the Second International Trans-anal Total Mesorectal Excision (TaTME) Conference held in Paris in July 2014. It outlines three facets of the TaTME procedure: (i) the technique and its indications, (ii) training and adoption, and (iii) data collection and the TaTME registry.

Therapeutic approach to Crohn disease: possible parallels with hidradenitis suppurativa. / Abordaje terapéutico de la enfermedad de Crohn: posibles paralelismos con la hidradenitis supurativa.

The current controversy in the setting of dermatology surrounding the treatment of inflammatory diseases, and specifically hidradenitis suppurativa, bears strong similarities with the debate concerning inflammatory bowel disease (IBD) that took place several years ago. That debate led to new perspectives on this disease and, in particular, its treatment after the development of biological agents.

Treatment of chronic radiation proctopathy with radiofrequency ablation (with video).

BACKGROUND: Chronic radiation proctopathy (CRP) is a common sequela occurring even many years after pelvic radiation. Current ablative therapies for bleeding ectatic vessels have the potential for deep tissue injury leading to ulcerations, perforation, and fistulas. Radiofrequency ablation (RFA) therapy avoids deep tissue injury and is a promising treatment for CRP. OBJECTIVE: To assess the long-term safety and efficacy of RFA for the treatment of CRP. DESIGN: Multicenter, retrospective analysis of a prospectively collected database. SETTING: Veterans Affairs Boston Healthcare System, Massachusetts; Sarasota Memorial Hospital and Suncoast Endoscopy of Sarasota, Florida. PATIENTS: A total of 39 consecutive patients with CRP. INTERVENTIONS: Endoscopic RFA of CRP. MAIN OUTCOME MEASUREMENTS: The primary endpoint of the study was complete resolution of rectal bleeding. Secondary endpoints included visually scored improvement of CRP on endoscopic follow-up by using a rectal telangiectasia density (RTD) grading score, improvement in hemoglobin level, and adverse events related to the procedure. RESULTS: A total of 39 male patients (mean [± standard deviation {SD}] age 72.9 ± 6.6 years) were included in the study. The mean number of RFA sessions was 1.49 (median 1, interquartile range [IQR] 1-2, range 1-4), with a mean interval of 18 weeks between sessions. Rectal bleeding stopped completely in all patients during the mean follow-up of 28 months (range 7-53 months). A significant improvement occurred in the mean (± SD) hemoglobin level from 11.8 ± 2 to 13.5 ± 1.6 g % (P < .0001). Endoscopic severity also improved significantly with an improvement in the median RTD score from 3 (IQR 2-3) to 0 (IQR 0-1) (P < .0001). Treatment with RFA led to discontinuation of blood transfusion and iron therapy in 92% and 82% patients, respectively. LIMITATIONS: Retrospective analysis, lack of control group. CONCLUSION: RFA therapy led to complete resolution of rectal bleeding in all treated CRP patients, with improvement in clinical and endoscopic indices without any major adverse events. Further controlled studies are needed to establish RFA as the endoscopic therapy of choice for treatment of CRP.

Sphincter-sparing intersphincteric rectal resection as an alternative to proctectomy in long-standing fistulizing and stenotic Crohn's proctitis?

PURPOSE: Long-standing fistulizing and stenotic proctitis (LFSP) in Crohn's disease (CD) indicates the end stage of the disease. Definitive diversion such as proctectomy is considered to be the only surgical option. The impact of intersphincteric sphincter-sparing anterior rectal resection (IAR) as an alternative to proctectomy is unclear. The aim of this study was to evaluate feasibility, morbidity, outcome, and quality of life (QL) in patients with LFSP undergoing intended IAR. PATIENTS AND METHODS: Out of a single institution database, 15 patients with LFSP intended for surgery from 856 patients with CD were selected for follow-up analyses. RESULTS: In 12/15 cases, IAR was carried out while 3/15 patients underwent primary proctectomy due to malignancy (n = 2) or due to patient's wish (n = 1). In one case, IAR revealed unexpected malignancy, which led to secondary proctectomy. In patients with IAR, complete healing of fistulas and stenosis was observed in 46% (n = 5) while 36% (n = 4) of patients showed relapse of fistula and 18% (n = 2) developed restenosis. Ileostomy closure was performed in seven patients from which six patients remained stoma free. QL and fecal incontinence measured by standardized scoring systems were unchanged while stool frequency was reduced after IAR in patients with ileostomy closure. The rate of malignancy in this cohort was 20% (n = 3). CONCLUSION: LFSP in CD was associated with 20% of malignant transformation. Although IAR fails to improve QL, it is a suitable procedure for the treatment of fistulas and stenosis associated with acceptable healing rates and can avoid a permanent stoma.

Factors affecting the fate of faecal diversion in patients with perianal Crohn's disease.

AIM: A study was carried out with the aim of identifying potential factors which might influence the fate of patients undergoing faecal diversion by stoma in perianal Crohn's disease. METHOD: Patients with severe perianal Crohn's disease undergoing faecal diversion between 1994 and 2012 were identified and the factors associated with stoma closure were assessed using univariate and multivariate analysis. RESULTS: Of 138 diverted patients, 30 (22%) achieved stoma closure, 45 (33%) had a stoma with the rectum left in situ and 63 (45%) underwent proctectomy with permanent stoma formation after a mean follow-up of 5.7 years. Univariate analysis demonstrated that synchronous colonic (P = 0.004) or rectal (P = 0.021) disease involvement and an increased frequency of loose seton placement (P = 0.001) adversely affected successful stoma closure rates. Multivariate analysis indicated a significant association between the inability to achieve stoma closure and persisting rectal involvement (OR 7.5, 95% CI 2.4-33.4), one or two placements of a loose seton (OR 3.3, 95% CI 1.4-8.8) and more than two placements (OR 6.9, 95% CI 1.2-132.5). No specific medical management was associated with an improved stoma closure rate, including biological agents when these were available (P = 0.25). CONCLUSION: The fate of temporary faecal diversion in patients with perianal Crohn's disease is adversely affected by aggressive disease characteristics. No particular treatment, including biological therapy, was associated with an improved outcome.

[New approaches in surgical treatment of acute paraproctitis].

The results of treatment of 77 patients, ageing 18-71 yrs old, for an acute paraproctitis in 2010-2014 yrs were analyzed. A preventive puncture-flush enzymosanation of purulent foci, using immobilized bacterial proteinases (imozimase), metrogyl P in conjunction with low-intensive laser irradiation have permitted to conduct the optimal preoperative preparation of patients, to improve their state, to reduce the local inflammatory reactions intensity significantly.

[IMMUNOHISTOCHEMICAL AND CYTOLOGICAL ASSESSMENT OF LOCAL INFLAMMATORY REACTION IN THE EARLY POSTOPERATIVE PERIOD IN PATIENTS UNDERGOING SURGERY FOR COMPLEX FORMS OF ACUTE PARAPROCTITIS].

The optimal time to fulfill the second (plastic) phase delayed early radical surgery in patients over the complicated forms of acute paraproctitis. On the 7th day after the opening of an abscess in a smear from the surface layer of the wound inflammatory regenerative cytogram type was observed in 66.8% of patients, early regenerative type--at 33.2%. On the 10th day was observed regenerative cytogram type. The dynamics of the concentration of cytokines in wound fluid on the 7th day showed a favorable course of wound healing process, without increasing the levels of proinflammatory cytokines, which allowed to perform the second stage of early delayed surgery in 7-10 days.

Radiofrequency ablation for the treatment of radiation proctitis.

BACKGROUND AND STUDY AIMS: The main endoscopic therapy for radiation proctitis is argon plasma coagulation (APC); however treatment is not always successful. Radiofrequency ablation (RFA) is a possible treatment for radiation proctitis but data are scarce. The aim of this study was to report on the safety and efficacy of RFA in the treatment of radiation proctitis. PATIENTS AND METHODS: This study was an open-label, retrospective, multicenter study of patients with chronic hemorrhagic radiation proctitis who were treated with RFA. Data included a three-item symptom score, the number of packed red blood cell transfusions, the lowest hemoglobin concentration, and complications, during the 6 months prior to and after RFA. Clinical success was defined as a decrease in the symptom score. Biological success was defined as an increase in the hemoglobin rate with equal or decreased number of transfusions required. RESULTS: A total of 17 patients underwent a median of 2 RFA sessions (range 1 - 4), without perioperative complications. Symptom scores decreased in 16 patients (clinical success 94 %), from a mean score of 3.6 (median 4) to 1.4 (median 1) (P < 0.01). Two patients developed rectal ulceration, with no local symptoms. During the 6 months after RFA, hemoglobin concentration increased in all 17 patients (from mean 8.3 ± 2.8 g/dL [median 7.5] to 11.3 ± 2.2 g/dL [median 11.0]; P < 0.01). Among 13 patients who were transfusion dependent prior to RFA (mean 7.2 ± 7.7 transfusions [median 4]), 9 patients (69 %) were weaned off transfusions after RFA. A significant increase in the hemoglobin level was observed in this subgroup of patients (from mean 7.2 ± 1.4 g/dL [median 7.3] to 10.7 ± 1.5 g/dL [median 10.5]; P < 0.001). Biological success was 100 %. CONCLUSIONS: RFA seems to significantly decrease clinical symptoms and increase the hemoglobin concentration, thus reducing the need for transfusions.

Managing intractable proctitis and the problematic pouch.

Proctitis accounts for a significant proportion of cases of ulcerative colitis (UC), and some patients subsequently develop more extensive disease. However, most patients continue to have limited inflammation, although the changes in the distal colon and rectum can occasionally be severe, and symptoms of increased frequency, rectal bleeding and urgency can be as disabling as they are for patients with more extensive colitis. Furthermore, although symptoms are typically well controlled with standard medications, medically refractory proctitis poses particular problems. Patients generally are not systemically unwell, and there is no added fear of cancer. Therefore, the prospect of colectomy for such limited disease is resisted by patients, physicians and surgeons alike. Unusual therapies, often delivered locally by enema or suppository, have been tested in small case series without definitive outcomes. The pathogenesis of such limited, yet intractable inflammation remains unclear, and the differential diagnosis should be carefully reviewed to ensure that local disease, whether it is infectious, vascular, or a result of injury or degeneration, is not overlooked. Ileo-anal pouch formation is the surgery of choice for about 20% of patients with UC who undergo colectomy. In the majority of cases, this surgery results in an acceptable quality of life and freedom from a stoma. However, in a sizeable minority of cases, pouch dysfunction can cause intractable problems. The causes of pouch dysfunction are varied and must all be considered carefully, particularly in refractory cases. Pouchitis is a common issue and is usually transient and easily treated. However, refractory and chronic pouchitis can be challenging. Ischaemia, injury, infection and Crohn's disease can all cause refractory pouch dysfunction. In a minority of cases, there appears to be no apparent organic pathology, and the presumptive diagnosis is that of a functional pouch disorder. Although it is much rarer, neoplastic changes in the pouch must also be considered, and the risk managed appropriately. The management of both intractable proctitis and the problematic pouch is made more challenging by the wide differential diagnosis that must be considered and by the paucity of high-quality clinical trials to support any one therapy. Key strategies to overcoming these limitations include methodical and systematic investigation and review, and a willingness to tailor therapy to the individual patient. Clinical trials of new treatments should be supported, and data from the experience with small cohorts of patients should be meticulously collected, critically analysed and widely disseminated.