Adjuvant Radiotherapy in Stage II Endometrial Cancer: Selective De-intensification of Adjuvant Treatment.

AIMS: Risk stratification, including nodal assessment, allows for selective de-intensification of adjuvant radiotherapy in stage II endometrial cancer. Patterns of treatment and clinical outcomes, including the use of reduced volume 'mini-pelvis' radiotherapy fields, were evaluated in a population-based study. MATERIALS AND METHODS: All patients diagnosed with pathological stage II endometrial cancer between 2000 and 2014, and received adjuvant radiotherapy in a regional healthcare jurisdiction were reviewed. Registry data were supplemented by a comprehensive review of patient demographics, disease characteristics and treatment details. The Charlson Comorbidity Score was calculated. Survival and recurrence data were analysed. RESULTS: In total, 264 patients met the inclusion criteria. Most patients had endometrioid histology (83%); 41% of patients had International Federation of Gynecologists and Obstetricians grade 1 disease. Half (49%) had surgical nodal evaluation; 11% received chemotherapy. Most patients (59%) were treated with full pelvic radiotherapy fields ± brachytherapy. Seventeen per cent of patients received mini-pelvis radiotherapy ± brachytherapy, whereas 24% received brachytherapy alone. Five-year recurrence-free survival was 87% for the entire cohort, with no significant difference by adjuvant radiotherapy approach. Only one patient receiving mini-pelvis radiotherapy ± brachytherapy recurred in the pelvis but outside of the mini-pelvis field. Recorded late toxicity rates were highest for full pelvis radiotherapy + brachytherapy. CONCLUSION: Risk stratification in a real-world setting allowed for selective de-intensification of adjuvant radiation with equivalent outcomes for stage II endometrial cancer. Mini-pelvis radiotherapy combined with brachytherapy is effective in highly selected patients, with the potential to decrease toxicity without compromising local control. Brachytherapy should be considered in low-risk stage II patients.

Vaccination saves lives: a real-time study of patients with chronic diseases and severe COVID-19 infection.

OBJECTIVES: This study aims to describe the demographic and clinical profile and ascertain the determinants of outcome among hospitalized coronavirus disease 2019 (COVID-19) adult patients enrolled in the National Clinical Registry for COVID-19 (NCRC). METHODS: NCRC is an on-going data collection platform operational in 42 hospitals across India. Data of hospitalized COVID-19 patients enrolled in NCRC between 1st September 2020 to 26th October 2021 were examined. RESULTS: Analysis of 29 509 hospitalized, adult COVID-19 patients [mean (SD) age: 51.1 (16.2) year; male: 18 752 (63.6%)] showed that 15 678 (53.1%) had at least one comorbidity. Among 25 715 (87.1%) symptomatic patients, fever was the commonest symptom (72.3%) followed by shortness of breath (48.9%) and dry cough (45.5%). In-hospital mortality was 14.5% (n = 3957). Adjusted odds of dying were significantly higher in age group ≥60 years, males, with diabetes, chronic kidney diseases, chronic liver disease, malignancy and tuberculosis, presenting with dyspnoea and neurological symptoms. WHO ordinal scale 4 or above at admission carried the highest odds of dying [5.6 (95% CI: 4.6-7.0)]. Patients receiving one [OR: 0.5 (95% CI: 0.4-0.7)] or two doses of anti-SARS CoV-2 vaccine [OR: 0.4 (95% CI: 0.3-0.7)] were protected from in-hospital mortality. CONCLUSIONS: WHO ordinal scale at admission is the most important independent predictor for in-hospital death in COVID-19 patients. Anti-SARS-CoV2 vaccination provides significant protection against mortality.

Real-world experience with 0.2 µg/day fluocinolone acetonide intravitreal implant (ILUVIEN) in the United Kingdom.

AimsTo compare safety outcomes and visual function data acquired in the real-world setting with FAME study results in eyes treated with 0.2 µg/day fluocinolone acetonide (FAc).MethodsFourteen UK clinical sites contributed to pseudoanonymised data collected using the same electronic medical record system. Data pertaining to eyes treated with FAc implant for diabetic macular oedema (DMO) was extracted. Intraocular pressure (IOP)-related adverse events were defined as use of IOP-lowering medication, any rise in IOP>30 mm Hg, or glaucoma surgery. Other measured outcomes included visual acuity, central subfield thickness (CSFT) changes and use of concomitant medications.ResultsIn total, 345 eyes had a mean follow-up of 428 days. Overall, 13.9% of patients required IOP-lowering drops (included initiation, addition and switching of current drops), 7.2% had IOP elevation >30 mm Hg and 0.3% required glaucoma surgery. In patients with prior steroid exposure and no prior IOP-related event, there were no new IOP-related events. In patients without prior steroid use and without prior IOP-related events, 10.3% of eyes required IOP-lowering medication and 4.3% exhibited IOP >30 mm Hg at some point during follow-up. At 24 months, mean best-recorded visual acuity increased from 51.9 to 57.2 letters and 20.8% achieved ≥15-letter improvement. Mean CSFT reduced from 451.2 to 355.5 µm.ConclusionsWhile overall IOP-related emergent events were observed in similar frequency to FAME, no adverse events were seen in the subgroup with prior steroid exposure and no prior IOP events. Efficacy findings confirm that the FAc implant is a useful treatment option for chronic DMO.

Quantification of diffusion and anisotropy in intracranial epidermoids using diffusion tensor metrics and p: q tensor decomposition.

PURPOSE: To quantitatively evaluate the diffusion tensor metrics p, q, L and fractional anisotropy in intracranial epidermoids in comparison with normal white matter in the splenium of the corpus callosum. METHODS: This retrospective study included 20 consecutive patients referred to our institute. All patients had a magnetic resonance imaging (MRI) study on a 1.5-Tesla MR system. A spin-echo echo-planar DTI sequence with diffusion gradients along 30 non-collinear directions was performed. The eigen values (λ1, λ2, λ3) were computed for each voxel and, using p: q tensor decomposition, the DTI metrics p, q and L-values and fractional anositropy (FA) were calculated. The region of interest (ROI) (6 pixels each) was placed within the lesion in all the cases and in the splenium of the corpus callosum. RESULTS: The mean FA in the lesion and splenium were 0.50 and 0.88 respectively, with a statistically significant difference between them (P<0.01). On p: q tensor decomposition, the mean p-value in the epidermoid was 1.55±0.24 and 1.35±0.20 in the splenium; the mean q-values in the epidermoid was 0.67±0.13 and 1.27±0.17 in the splenium; the differences were statistically significant (P=0.01 and <0.01 respectively). The significant difference between p- and q-values in epidermoids compared with the splenium of callosum was probably due to structural and orientation differences in the keratin flakes in epidermoids and white matter bundles in the callosum. However, no significant statistical difference in L-values was noted (P=0.44). CONCLUSION: DTI metrics p and q have the potential to quantify the diffusion and anisotropy in various tissues thereby gaining information about their internal architecture. The results also suggest that significant differences of DTI metrics p and q between epidermoid and the splenium of the corpus callosum are due to the difference in structural organization within them.

A randomized clinical trial comparing fixed vs pro-re-nata dosing of Ozurdex in refractory diabetic macular oedema (OZDRY study).

OBJECTIVE: To compare the clinical effectiveness and safety of 5-monthly fixed dosing vs pro-re-nata (PRN) Ozurdex treatment in patients with refractory diabetic macular oedema (DMO). DESIGN: Prospective, multicentre, randomized active-controlled non-inferiority clinical trial. PARTICIPANTS: Participants were 100 patients who attended Medical Retina Clinics for management of centre-involving refractory DMO. INTERVENTIONS: Participants were randomized 1 : 1 to either 5-monthly fixed dosing or optical coherence tomography (OCT)-guided PRN regimen of Ozurdex therapy for DMO. Data were collected on best-corrected visual acuity (BCVA), patient-reported outcome measures (PROM), macular thickness and morphology, diabetic retinopathy status, number of injections and adverse events from baseline for a period of 12 months.Main outcome measuresThe primary outcome was the difference between arms in change in BCVA from baseline to 12 months. The prespecified non-inferiority margin was five ETDRS letters. Key secondary outcomes included change in PROM scores, change in macular thickness, change in retinopathy and macular morphology, and safety profile. RESULTS: The mean change in BCVA was +1.48 (SD 14.8) in the fixed arm vs -0.17 (SD 13.1) in the PRN arm, with adjusted effect estimate +0.97, 90% confidence interval (-4.01, +5.95), P=0.02 (per protocol analysis). The conclusions of the ITT analysis were primarily supportive, -0.34 (-5.49, 4.81) P=0.07, but sensitive to an alternative assumption on missing data, +0.28 (-4.72, 5.27) P=0.04. CONCLUSIONS: The mean change in BCVA with 5-monthly fixed dosing of Ozurdex was non-inferior to OCT-guided PRN Ozurdex therapy for refractory DMO based on a per protocol analysis.

Defining response to anti-VEGF therapies in neovascular AMD.

The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as 'responder status' after treatment for n-AMD, 'tachyphylaxis' and 'recalcitrant' n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when there is resolution of fluid (intraretinal fluid; IRF, subretinal fluid; SRF and retinal thickening), and/or improvement of >5 letters, subject to the ceiling effect of good starting VA. Poor response is defined as <25% reduction from the baseline in the central retinal thickness (CRT), with persistent or new IRF, SRF or minimal or change in VA (that is, change in VA of 0+4 letters). Non-response is defined as an increase in fluid (IRF, SRF and CRT), or increasing haemorrhage compared with the baseline and/or loss of >5 letters compared with the baseline or best corrected vision subsequently. Poor or non-response to anti-VEGF may be due to clinical factors including suboptimal dosing than that required by a particular patient, increased dosing intervals, treatment initiation when disease is already at an advanced or chronic stage), cellular mechanisms, lesion type, genetic variation and potential tachyphylaxis); non-clinical factors including poor access to clinics or delayed appointments may also result in poor treatment outcomes. In eyes classified as good responders, treatment should be continued with the same agent when disease activity is present or reactivation occurs following temporary dose holding. In eyes that show partial response, treatment may be continued, although re-evaluation with further imaging may be required to exclude confounding factors. Where there is persistent, unchanging accumulated fluid following three consecutive injections at monthly intervals, treatment may be withheld temporarily, but recommenced with the same or alternative anti-VEGF if the fluid subsequently increases (lesion considered active). Poor or non-response to anti-VEGF treatments requires re-evaluation of diagnosis and if necessary switch to alternative therapies including other anti-VEGF agents and/or with photodynamic therapy (PDT). Idiopathic polypoidal choroidopathy may require treatment with PDT monotherapy or combination with anti-VEGF. A committee comprised of retinal specialists with experience of managing patients with n-AMD similar to that which developed the Royal College of Ophthalmologists Guidelines to Ranibizumab was assembled. Individual aspects of the guidelines were proposed by the committee lead (WMA) based on relevant reference to published evidence base following a search of Medline and circulated to all committee members for discussion before approval or modification. Each draft was modified according to feedback from committee members until unanimous approval was obtained in the final draft. A system for categorising the range of responsiveness of n-AMD lesions to anti-VEGF therapy is proposed. The proposal is based primarily on morphological criteria but functional criteria have been included. Recommendations have been made on when to consider discontinuation of therapy either because of success or futility. These guidelines should help clinical decision-making and may prevent over and/or undertreatment with anti-VEGF therapy.

Wide-field imaging and OCT vs clinical evaluation of patients referred from diabetic retinopathy screening.

PURPOSE: Compare wide-field Optomap imaging and optical coherence tomography (OCT) with clinical examination in diabetic retinopathy (DR). METHODS: Patients referred from Diabetic Eye Screening Programmes to three centres underwent dilated ophthalmoscopy and were assigned a DR grade. Wide-field colour imaging and OCT were then examined by the same clinician at that visit and a combined grade was assigned. Independent graders later reviewed the images and assigned an imaging-only grade. These three grades (clinical, combined, and imaging) were compared. The method that detected the highest grade of retinopathy, including neovascularisation, was determined. RESULTS: Two thousand and forty eyes of 1023 patients were assessed. Wide-field imaging compared with clinical examination had a sensitivity and specificity of 73% and 96%, respectively, for detecting proliferative DR, 84% and 69% for sight-threatening DR, and 64% and 90% for diabetic macular oedema. Imaging alone found 35 more eyes with new vessels (19% of eyes with new vessels) and the combined grade found 14 more eyes than clinical examination alone. CONCLUSIONS: Assessment of wide-field images and OCT alone detected more eyes with higher grades of DR compared with clinical examination alone or when combined with imaging in a clinical setting. The sensitivity was not higher as the techniques were not the same, with imaging alone being more sensitive. Wide-field imaging with OCT could be used to assess referrals from DR screening to determine management, to enhance the quality of assessment in clinics, and to follow-up patients whose DR is above the screening referral threshold but does not actually require treatment.

Kikuchi-Fujimoto Disease: part of the differential diagnosis of cervical lymphadenopathy in an HIV-positive patient.

A 38-year-old HIV-positive Nigerian woman presented with a three-week history of cervical lymphadenopathy, night sweats, weight loss and fever. Provisional diagnoses of tuberculosis and lymphoma were considered; however, a histological diagnosis of Kikuchi-Fujimoto Disease was reached. This rare benign disease has presenting features that mimic more serious conditions commonly occurring in HIV-positive patients. This case report emphasises the importance of Kikuchi-Fujimoto Disease in the differential diagnosis of cervical lymphadenopathy in HIV-positive patients.

EC-IC bypass for cavernous carotid aneurysms: An initial experience with twelve patients.

AIMS: Need for performing a bypass procedure prior to parent artery occlusion in patients with good cerebral vascular reserve is controversial. We analyze our experience of 12 giant internal carotid artery aneurysms treated with extracranial-intracranial (EC-IC) bypass and proximal artery occlusion. MATERIALS AND METHODS: Retrospective analysis of the case records of all complex carotid aneurysms operated in our institute since January 2009. RESULTS: The study included eleven cavernous carotid aneurysms and one large fusiform cervical carotid aneurysm reaching the skull base. Preoperative assessment of cerebral vascular reserve was limited to Balloon test occlusion with hypotensive challenge. Eleven patients who successfully completed a Balloon test occlusion (BTO) underwent low flow superficial temporal artery to middle cerebral artery (STA-MCA) bypass, while one patient with a failed BTO underwent a high flow bypass using a saphenous vein graft. Parent artery ligation was performed in all patients following the bypass procedure. Check angiogram revealed thrombosis of the aneurysm in all patients with a graft patency rate of 81.8%. We had one operative mortality, probably related to a leak from the anastomotic site. The only patient who had a high flow bypass developed contralateral hemispheric infarcts and remained vegetative. All the other patients had a good recovery and with a Glasgow outcome score of 5 at last follow-up. CONCLUSION: We feel that combining EC-IC bypass prior to parent vessel occlusion helps in reducing the risk of post operative ischemic complications especially in situations where a complete mandated cerebral blood flow studies are not feasible.

Ultrastructure of skin from Refsum disease with emphasis on epidermal lamellar bodies and stratum corneum barrier lipid organization.

Classic Refsum disease (RD) is a rare, autosomal recessively-inherited disorder of peroxisome metabolism due to a defect in the initial step in the alpha oxidation of phytanic acid (PA), a C16 saturated fatty acid with four methyl side groups, which accumulates in plasma and lipid enriched tissues (please see van den Brink and Wanders, Cell Mol Life Sci 63:1752-1765, 2006). It has been proposed that the disease complex in RD is in part due to the high affinity of phytanic acid for retinoid X receptors and peroxisome proliferator-activated receptors. Structurally, epidermal hyperplasia, increased numbers of cornified cell layers, presence of cells with lipid droplets in stratum basale and reduction of granular layer to a single layer have been reported by Blanchet-Bardon et al. (The ichthyoses, SP Medical & Scientific Books, New York, pp 65-69, 1978). However, lamellar body (LB) density and secretion were reportedly normal. We recently examined biopsies from four unrelated patients, using both OsO4 and RuO4 post-fixation to evaluate the barrier lipid structural organization. Although lamellar body density appeared normal, individual organelles often had distorted shape, or had non-lamellar domains interspersed with lamellar structures. Some of the organelles seemed to lack lamellar contents altogether, showing instead uniformly electron-dense contents. In addition, we also observed mitochondrial abnormalities in the nucleated epidermis. Stratum granulosum-stratum corneum junctions also showed co-existence of non-lamellar and lamellar domains, indicative of lipid phase separation. Also, partial detachment or complete absence of corneocyte lipid envelopes (CLE) was seen in the stratum corneum of all RD patients. In conclusion, abnormal LB contents, resulting in defective lamellar bilayers, as well as reduced CLEs, likely lead to impaired barrier function in RD.

Extraventricular neurocytoma, a comprehensive review.

AIMS AND OBJECTIVE: Extra ventricular neurocytoms (EVN) are a rare parenchymal brain tumour distinct from central neurocytomas. This review attempts to analyze a series of seven cases of EVN from a single institute against the background of available literature. METHOD: Retrospective analysis of the clinical manifestation, pathological features, imaging findings, microsurgical treatment effectiveness and progression free survival of seven cases of EVN operated between 2000-2012. RESULTS: The study group included five females and two males in the age group 7-65 years (mean 30.71 yrs). The distribution of the lesion was as follows Lobar 4, Cerebellum 1, Pineal 1, spinal 1. The duration of clinical symptoms ranged from three months to seven years and the presentation was site and size specific. Cystic Changes (71 %), perilesional oedema (57 %) and heterogeneous contrast enhancement (85.7 %), and calcification (42 %) were a few distinct imaging characteristics. Increased perfusion correlated with atypical histology in two patients. Surgical resection remains the main management strategy for longer outcome and patients with STR + RT and GTR had comparable follow-up. Extremes of age and atypical histological features were adverse prognostic factors. CONCLUSION: EVN are rare tumors with either glial or neuronal differentiation or a potential for atypical changes. Both, GTR and STR combined with RT, offer reasonably good outcome with overall comparable survival. The available literature of EVN is limited, larger series with long term follow-ups are needed to dictate the management protocol. The role of adjuvant therapy is still debatable and needs further validation.

Anaplastic large cell lymphoma in a reconstructed breast using a silicone implant: a UK case report.

We present case of Anaplastic Large Cell Lymphoma discovered as an incidental finding whilst revising an implant based breast reconstruction in a 55 year old woman, whom previously had undergone risk reduction mastectomies and immediate reconstruction. During the procedure a presumed seroma was present but this was macroscopically atypical giving a 'milky' coloured appearance with a pink tinge to it. The atypical fluid was sent for analysis and the diagnosis of ALCL confirmed. Treatment consisted of unilateral capsulectomy on the affected side and bilateral removal of implants with staging scans suggesting the disease being confined to the capsule. She remains in remission 12 months following the original procedure.

Is it necessary to use three mandatory loading doses when commencing therapy for neovascular age-related macular degeneration using bevacizumab? (BeMOc Trial).

PURPOSE: To determine whether a Pro Re Nata (PRN) regimen with three initial mandatory loading doses results in better functional and anatomical outcome compared with a PRN regimen without initial loading when using intravitreal bevacizumab in patients with minimal classic or occult choroidal neovascularisation secondary to age-related macular degeneration. METHODS: Patients were randomised (1 : 1) to Loading (LD group) or No Loading (NLD group) and treated with open label intravitreal bevacizumab. In the LD group, patients received two mandatory doses after the baseline dose before entering the PRN phase and in the NLD group, patients did not receive mandatory doses after the baseline dose. Six-weekly evaluations were performed up to week 54 and retreatment was done based on OCT criteria. Visual stability and reduction in central retinal thickness were compared between groups. RESULTS: 49 patients were in the NLD group and 50 patients were in the LD group. At the 12-month end point, 84% of the patients in the LD group achieved visual stability (<15 letter loss) compared with 67% of the patients in the NLD group (P<0.05). The mean reduction in central macular thickness was 105.35 µm in the LD group and 81.45 µm in the NLD group (P>0.05). There was no significant difference in scores of VFQ-25 questionnaire testing between the two groups and no serious ocular or systemic side effects were observed. CONCLUSION: The results supported our hypothesis that a loading dose leads to slightly better visual stability in terms of proportions of patients experiencing moderate visual loss, but did not support the hypothesised difference in anatomical outcome.

Ranibizumab for the treatment of choroidal neovascularisation secondary to pathological myopia: interim analysis of the REPAIR study.

AIMS: To evaluate the efficacy and safety of intravitreal ranibizumab in patients with choroidal neovascularisation secondary to pathological myopia (myopic CNV). Data are from a pre-planned, 6-month interim analysis. METHODS: Phase II, open-label, single arm, multicentre, 12-month study, recruiting patients (aged ≥18 years) with active primary or recurrent subfoveal or juxtafoveal myopic CNV, with a best-corrected visual acuity (BCVA) score of 24-78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye and a diagnosis of high myopia of at least -6 dioptres. Patients received 0.5 mg ranibizumab administered intravitreally to the study eye, followed by monthly injections given as needed (based on a predefined algorithm) for up to 11 months. RESULTS: At 6 months, mean BCVA improved from baseline by 12.2 letters, as did central macular thickness (in this interim analysis defined as a measure of either central subfield macular thickness or centre point macular thickness) from baseline by 108 µm in the 48 study eyes of 48 patients. Fewer patients had centre-involving intraretinal oedema (13.0% vs 91.5%), intraretinal cysts (10.9% vs 57.4%), or subretinal fluid (13.0% vs 66.0%) at 6 months than at baseline. Patients received a mean of 1.9 retreatments, were satisfied with ranibizumab treatment, and well being was maintained. No new safety signals were identified. CONCLUSIONS: Results from the planned interim analysis support the role of ranibizumab in the treatment of myopic CNV, with excellent efficacy achieved with a low number of injections and few serious adverse events.

Muon-spin rotation measurements of an unusual vortex-glass phase in the layered superconductor Bi2.15Sr1.85CaCu2O8+δ.

Muon-spin rotation measurements, performed on the mixed state of the classic anisotropic superconductor Bi(2.15)Sr(1.85)CaCu(2)O(8+δ), obtain quantities directly related to two- and three-body correlations of vortices in space. A novel phase diagram emerges from such local probe measurements of the bulk, revealing an unusual glassy state at intermediate fields which appears to freeze continuously from the equilibrium vortex liquid but differs both from the lattice and the conventional high-field vortex glass state in its structure.

Long-term continence disturbance after lateral internal sphincterotomy for chronic anal fissure: a systematic review and meta-analysis.

AIM: A systematic review was carried out to analyse continence at 2 years or more after lateral internal sphincterotomy (LIS) for chronic anal fissure (CAF). METHOD: PubMed, MEDLINE, Scopus, Embase, Ovid, SCI, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar were used to search the literature from 1969-2012 for studies reporting a follow-up of more than 2 years after LIS for CAF. The primary outcome parameter analysed was continence. The secondary outcome parameters included success rate, recurrence, incidence of postoperative abscess and fistula formation and patient satisfaction. RESULTS: Of 324 studies screened, 22 (n = 4512) were included. The mean follow-up period ranged from 24-124 months. The overall continence disturbance rate was 14% (95% CI 0.09-0.2). Weighted analysis showed flatus incontinence in 9% (95% CI 0.04-0.16), soilage/seepage in 6% (95% CI 0.03-0.1), accidental defaecation in 0.91% (95% CI 0.003-0.02), incontinence to liquid stool in 0.67% (95% CI 0.001-0.02) and incontinence to solid stool in 0.83% (95% CI 0.003-0.02) of patients. CONCLUSION: The long-term risk of continence disturbance after lateral internal sphincterotomy is significant. Randomized controlled trials with a long follow-up are needed to substantiate these findings and to redefine its role in the treatment of chronic anal fissure.