Neoadjuvant Radiotherapy Dose Escalation in Locally Advanced Rectal Cancer: a Systematic Review and Meta-analysis of Modern Treatment Approaches and Outcomes.

AIMS: Improving pathological complete response (pCR) rates after neoadjuvant chemoradiotherapy for locally advanced rectal cancer may facilitate surgery-sparing treatment paradigms. Radiotherapy boost has been linked to higher rates of pCR; however, outcomes in moderately escalated inverse-planning studies have not been systematically evaluated. We therefore carried out a systematic review and meta-analysis of radiation dose-escalation studies in the context of neoadjuvant therapy for locally advanced rectal cancer. MATERIALS AND METHODS: A systematic search of Pubmed, EMBASE and Cochrane databases for synonyms of 'rectal cancer', 'radiotherapy' and 'boost' was carried out. Studies were screened for radiotherapy prescription >54 Gy. Prespecified quality assessment was carried out for meta-analysis inclusion suitability. Pooled estimates of pCR, acute toxicity (grade ≥3) and R0 resection rates were determined with random-effects restricted maximum-likelihood estimation. Heterogeneity was assessed with Higgins I2 and Cochran Q statistic. Subset analysis examined outcomes in modern inverse-planning studies. Meta-regression with permutation correction was carried out for each outcome against radiation dose, radiotherapy technique, boost technique, chemotherapy intensification and other patient- and treatment-related cofactors. RESULTS: Forty-nine primary and three follow-up publications were included in the systematic review. Pooled estimates of pCR, toxicity and R0 resection across 37 eligible publications (n = 1817 patients) were 24.1% (95% confidence interval 21.2-27.4%), 11.2% (95% confidence interval 7.2-17.0%) and 90.7% (95% confidence interval 87.9-93.8%). Within inverse-planning studies (17 publications, n = 959 patients), these rates were 25.7% (95% confidence interval 21.0-31.1%), 9.8% (95% confidence interval 4.6-19.7%) and 95.3% (95% confidence interval 91.6-97.4%). Regression analysis did not identify any significant predictor of pCR (P > 0.05). CONCLUSIONS: Radiotherapy dose escalation above 54 Gy is associated with high rates of pCR and does not seem to increase the risk of acute grade ≥3 toxicity events. pCR rates approaching 25% may be achievable utilising moderate escalation (54-60 Gy) with modern inverse-planning techniques; however, a clear dose-response relationship was not identified in regression analysis and additional evidence is awaited given the prevalence of heterogenous single-arm studies to date.

A Review of Modern Radiation Therapy Dose Escalation in Locally Advanced Head and Neck Cancer.

The management of head and neck cancer is complex and often involves multimodality treatment. Certain groups of patients, such as those with inoperable or advanced disease, are at higher risk of treatment failure and may therefore benefit from radiation therapy dose escalation. This can be difficult to achieve without increasing toxicity. However, the combination of modern treatment techniques and increased research into the use of functional imaging modalities that assist with target delineation allows researchers to push this boundary further. This review aims to summarise modern dose escalation trials to identify the impact on disease outcomes and explore the growing role of functional imaging modalities. Studies experimenting with dose escalation above standard fractionated regimens as outlined in National Comprehensive Cancer Network guidelines using photon therapy were chosen for review. Seventeen papers were considered suitable for inclusion in the review. Eight studies investigated nasopharyngeal cancer, with the remainder treating a range of subsites. Six studies utilised functional imaging modalities for target delineation. Doses as high as 85.9 Gy in 2.6 Gy fractions (EQD2 90.2 Gy10) were reportedly delivered with the aid of functional imaging modalities. Dose escalation in nasopharyngeal cancer resulted in 3-year locoregional control rates of 86.6-100% and overall survival of 82-95.2%. For other mucosal primary tumour sites, 3-year locoregional control reached 68.2-85.9% and 48.4-54% for overall survival. There were no clear trends in acute or late toxicity across studies, regardless of dose or addition of chemotherapy. However, small cohort sizes and short follow-up times may have resulted in under-reporting. This review highlights the future possibilities of radiation therapy dose escalation in head and neck cancer and the potential for improved target delineation with careful patient selection and the assistance of functional imaging modalities.

Standards in Operation Notes--Is It Time to Re-Emphasise Their Importance?

Guidelines exist for operation notes from the Royal College of Surgeons of England but compliance has been shown to be variable. The authors performed a closed loop audit of compliance with RCS standards in an Irish Plastic Surgery department. Thirty random operation notes were selected from a conserved pool of authors--before and after an educational intervention to increase awareness of the RCS guidelines. Following education, improvements were noted but also deteriorations--time increased from 12 (40%) to 16 (53%), emergency/elective status from none (0%) to 11 (36%), and operative diagnosis from seven (23%) to 21 (70%). However notably among the findings, surgeon's name decreased from 30 (100%) to 26 (86%), findings from 27 (90%) to 21 (53%) and tissue altered from 27 (90%) to 20 (66%). As some specialities are developing operation note standards specific to individual procedures, the findings are compared with previous similar published work.

The epidemiology and mortality of pretibial lacerations.

Pretibial lacerations are common injuries which have an underestimated mortality associated with their occurrence, and an under-appreciated morbidity associated with their treatment - they account for 5.2 out of every 1000 Emergency Department attendances in the United Kingdom, and occur mostly in the elderly. They are also increasingly being referred to plastic surgery units - the authors' department saw an increase from 58 referrals in twelve months in 2005/2006 to 113 referrals in six months in 2011. The Queen Victoria Hospital, East Grinstead, follows an evidence based and multi-disciplinary practice for the treatment of these injuries. The authors present the outcomes of patients referred to the hospital from the community and treated according to these guidelines, and compares the outcomes and mortality to a period prior to the introduction of this practise. The average time for skin grafted wounds to heal is found to be 59.8 days and for the donors it is 50.3 days, compared with an average time to healing of 123 days for those managed conservatively. The one month and one year mortality associated with these injuries is highlighted, as is the reduction in these figures following the adherence to the current treatment regime - prior to its introduction the 31 day mortality was 15%, and this was reduced to 4.3% by achievable changes in practice and treatment. Finally, the relevant extant research literature regarding pretibial lacerations is reviewed.

Nfkb1 is a haploinsufficient DNA damage-specific tumor suppressor.

NF-κB proteins play a central and subunit-specific role in the response to DNA damage. Previous work identified p50/NF-κB1 as being necessary for cytotoxicity in response to DNA alkylation damage. Given the importance of damage-induced cell death for the maintenance of genomic stability, we examined whether Nfkb1 acts as a tumor suppressor in the setting of alkylation damage. Hprt mutation analysis demonstrates that Nfkb1(-/-) cells accumulate more alkylator-induced, but not ionizing radiation (IR)-induced, mutations than similarly treated wild-type cells. Subsequent in vivo tumor induction studies reveal that following alkylator treatment, but not IR, Nfkb1(-/-) mice develop more lymphomas than similarly treated Nfkb1(+/+) animals. Heterozygous mice develop lymphomas at an intermediate rate and retain functional p50 in their tumors, indicating that Nfkb1 acts in a haploinsufficient manner. Analysis of human cancers, including therapy-related myeloid neoplasms, demonstrates that NFKB1 mRNA expression is downregulated compared with control samples in multiple hematological malignancies. These data indicate that Nfkb1 is a haploinsufficient, pathway-specific tumor suppressor that prevents the development of hematologic malignancy in the setting of alkylation damage.

Tuberculous dactylitis in the setting of low serum vitamin D: a case report.

We present the case of a previously well patient who presented to the Emergency Department of a Dublin hospital with a tuberculous infection of his dominant index finger and a very low serum vitamin D level--this has been implicated in both primary and reactivation infections with Mycobacterium Tuberculosis. This case highlights and reviews both the importance of considering non-endemic pathologies in the setting of a patient base of diverse ethnicity, and the emerging importance of vitamin D in the immune response to M. tuberculosis infection. We discuss the relevant literature to highlight the background of this disease process, and the importance of a multidisciplinary approach to these patients.

Cell-penetrating peptides, electroporation and drug delivery.

Certain short polycations, such as trans-activating transcriptional activator and oligoarginine, rapidly pass through the plasma membranes of mammalian cells by a mechanism called transduction, as well as by endocytosis and macropinocytosis. These cell-penetrating peptides can carry with them cargos of 30 amino acids, more than the nominal limit of 500 Da and enough to be therapeutic. An analysis of the electrostatics of a charge outside the cell membrane and some recent experiments suggest that transduction may proceed by molecular electroporation. Ways to target diseased cells, rather than all cells, are discussed.

Simple model of the transduction of cell-penetrating peptides.

Cell-penetrating peptides (CPPs) such as HIV's trans-activating transcriptional activator (TAT) and polyarginine rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction. They may be medically useful when fused to well-chosen chains of fewer than about 35 amino acids. The author offers a simple model of transduction in which phosphatidylserines and CPPs effectively form two plates of a capacitor with a voltage sufficient to cause the formation of transient pores (electroporation). The model is consistent with experimental data on the transduction of oligoarginine into mouse C(2)C(12) myoblasts and makes three testable predictions. [Includes supplementary material].

Mass media interventions for smoking cessation in adults.

BACKGROUND: Mass media tobacco control campaigns can reach large numbers of people. Much of the literature is focused on the effects of tobacco control advertising on young people, but there are also a number of evaluations of campaigns targeting adult smokers, which show mixed results. Campaigns may be local, regional or national, and may be combined with other components of a comprehensive tobacco control policy. OBJECTIVES: To assess the effectiveness of mass media interventions in reducing smoking among adults. SEARCH STRATEGY: The Cochrane Tobacco Addiction Group search strategy was combined with additional searches for any studies that referred to tobacco/smoking cessation, mass media and adults. We also searched the Cochrane Register of Controlled Trials (CENTRAL) and a number of electronic databases. The last search was carried out in March 2007. SELECTION CRITERIA: Controlled trials allocating communities, regions or states to intervention or control conditions; interrupted time series.Adults, 25 years or older, who regularly smoke cigarettes. Studies which cover all adults as defined in studies were included. Mass media are defined here as channels of communication such as television, radio, newspapers, billboards, posters, leaflets or booklets intended to reach large numbers of people, and which are not dependent on person-to-person contact. The purpose of the mass media campaign must be primarily to encourage smokers to quit. They could be carried out alone or in conjunction with tobacco control programmes.The primary outcome was change in smoking behaviour. This could be reported as changes in prevalence, changes in cigarette consumption, quit rates, odds of being a smoker. DATA COLLECTION AND ANALYSIS: Two authors independently assessed all studies for inclusion criteria and for study quality. One author (MB) extracted data, and a second author (LS) checked them.Results were not pooled due to heterogeneity of included studies and are presented narratively and in table form. MAIN RESULTS: Eleven campaigns met the inclusion criteria for this review. Studies differed in design, settings, duration, content and intensity of intervention, length of follow up, methods of evaluation and also in definitions and measures of smoking behaviour used. Among nine campaigns reporting smoking prevalence, significant decreases were observed in the California and Massachusetts statewide tobacco control campaigns compared with the rest of the USA. Some positive effects on prevalence in the whole population or in the subgroups were observed in three of the remaining seven studies. Three large-scale campaigns of the seven presenting results for tobacco consumption found statistically significant decreases. Among the seven studies presenting abstinence or quit rates, four showed some positive effect, although in one of them the effect was measured for quitting and cutting down combined. Among the three that did not show significant decreases, one demonstrated a significant intervention effect on smokers and ex-smokers combined. AUTHORS' CONCLUSIONS: There is evidence that comprehensive tobacco control programmes which include mass media campaigns can be effective in changing smoking behaviour in adults, but the evidence comes from a heterogeneous group of studies of variable methodological quality. One state-wide tobacco control programme (Massachusetts) showed positive results up to eight years after the campaign, while another (California) showed positive results only during the period of adequate funding and implementation. Six of nine studies carried out in communities or regions showed some positive effects on smoking behaviour and at least one significant change in smoking prevalence (Sydney). The intensity and duration of mass media campaigns may influence effectiveness, but length of follow up and concurrent secular trends and events can make this difficult to quantify. No consistent relationship was observed between campaign effectiveness and age, education, ethnicity or gender.

Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation.

BACKGROUND: Rimonabant is a selective type 1 cannabinoid (CB1) receptor antagonist. It may assist with smoking cessation by restoring the balance of the endocannabinoid system, which can be disrupted by prolonged use of nicotine. Rimonabant also seeks to address many smokers' reluctance to persist with a quit attempt because of concerns about weight gain. OBJECTIVES: To determine whether selective CB1 receptor antagonists increase the numbers of people stopping smoking. To assess their effects on weight change in successful quitters and in those who try to quit but fail. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Review Group specialized register for trials, using the terms 'rimonabant' and 'smoking' in the title or abstract, or as keywords. We also searched MEDLINE, EMBASE, CINAHL and PsycINFO, using major MESH terms. We acquired electronic or paper copies of posters of preliminary trial results presented at the American Thoracic Society Meeting in 2005, and at the Society for Research on Nicotine and Tobacco European Meeting 2006. We also attempted to contact the authors of ongoing studies of rimonabant, and Sanofi Aventis (manufacturers of rimonabant). SELECTION CRITERIA: Types of studies: Randomized controlled trials. TYPES OF PARTICIPANTS: Adult smokers. Types of interventions: Selective CB1 receptor antagonists, such as rimonabant. Types of outcome measures: The primary outcome is smoking status at a minimum of six months after the start of treatment. We preferred sustained cessation rates to point prevalence, and biochemically verified cessation to self-reported quitting. We regarded smokers who drop out or are lost to follow up as continuing smokers. We have noted any adverse effects of treatment.A secondary outcome is weight change associated with the cessation attempt. DATA COLLECTION AND ANALYSIS: Two authors checked the abstracts for relevance, and attempted to acquire full trial reports. One author extracted the data, and a second author checked them. MAIN RESULTS: We found three trials which met our inclusion criteria, covering 1567 smokers (cessation: STRATUS-EU and STRATUS-US), and 1661 quitters (relapse prevention: STRATUS-WW). At one year, the pooled odds ratio (OR) for quitting with rimonabant 20 mg was 1.61 (95% confidence interval (CI) 1.12 to 2.30). No significant benefit was demonstrated for rimonabant at 5 mg dosage. Adverse events included nausea and upper respiratory tract infections. In the relapse prevention trial, smokers who had quit on the 20 mg regimen were 1(1/2) times more likely to remain abstinent on either active regimen than on placebo; the OR for the 20 mg maintenance group was 1.49 (95% CI 1.09 to 2.04, and for the 5 mg maintenance group 1.51 (95% CI 1.11 to 2.07). There appeared to be no significant benefit of maintenance treatment for the 5 mg quitters. Weight gain was reported to be significantly lower among the 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight, while normal weight smokers did not. AUTHORS' CONCLUSIONS: From the preliminary trial reports available, rimonabant 20 mg may increase the odds of quitting approximately 1(1/2)-fold. Adverse events include nausea and upper respiratory tract infections; the risk of serious adverse events is reported to be low. However, there is current concern (August 2007) over rates of depression and suicidal thoughts in people taking rimonabant for weight control. The evidence for rimonabant in maintaining abstinence is inconclusive. Rimonabant 20 mg may moderate weight gain in the long term.

Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation.

BACKGROUND: Rimonabant is a selective type 1 cannabinoid (CB1) receptor antagonist. It may assist with smoking cessation by restoring the balance of the endocannabinoid system, which can be disrupted by prolonged use of nicotine. Rimonabant also seeks to address many smokers' reluctance to persist with a quit attempt because of concerns about weight gain. OBJECTIVES: To determine whether selective CB1 receptor antagonists increase the numbers of people stopping smoking. To assess their effects on weight change in successful quitters and in those who try to quit but fail. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Review Group specialized register for trials, using the terms 'rimonabant' and 'smoking' in the title or abstract, or as keywords. We also searched MEDLINE, EMBASE, CINAHL and PsycINFO, using major MESH terms. We acquired electronic or paper copies of posters of preliminary trial results presented at the American Thoracic Society Meeting in 2005, and at the Society for Research on Nicotine and Tobacco European Meeting 2006. We also attempted to contact the authors of ongoing studies of rimonabant, and Sanofi Aventis (manufacturers of rimonabant). SELECTION CRITERIA: Types of studies: Randomized controlled trials. TYPES OF PARTICIPANTS: Adult smokers. Types of interventions: Selective CB1 receptor antagonists, such as rimonabant. Types of outcome measures: The primary outcome is smoking status at a minimum of six months after the start of treatment. We preferred sustained cessation rates to point prevalence, and biochemically verified cessation to self-reported quitting. We regarded smokers who drop out or are lost to follow up as continuing smokers. We have noted any adverse effects of treatment. A secondary outcome is weight change associated with the cessation attempt. DATA COLLECTION AND ANALYSIS: Two authors checked the abstracts for relevance, and attempted to acquire full trial reports. One author extracted the data, and a second author checked them. MAIN RESULTS: We found three trials which met our inclusion criteria, covering 1567 smokers (cessation: STRATUS-EU and STRATUS-US), and 1661 quitters (relapse prevention: STRATUS-WW). At one year, the pooled odds ratio (OR) for quitting with rimonabant 20 mg was 1.61 (95% confidence interval (CI) 1.12 to 2.30). No significant benefit was demonstrated for rimonabant at 5 mg dosage. Adverse events included nausea and upper respiratory tract infections. In the relapse prevention trial, smokers who had quit on the 20 mg regimen were 1(1/2) times more likely to remain abstinent on either active regimen than on placebo; the OR for the 20 mg maintenance group was 1.49 (95% CI 1.09 to 2.04, and for the 5 mg maintenance group 1.51 (95% CI 1.11 to 2.07). There appeared to be no significant benefit of maintenance treatment for the 5 mg quitters.Weight gain was reported to be significantly lower among the 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight, while normal weight smokers did not. AUTHORS' CONCLUSIONS: From the preliminary trial reports available, rimonabant 20 mg may increase the odds of quitting approximately 1 and one-half-fold. Adverse events include nausea and upper respiratory tract infections; the risk of serious adverse events is reported to be low. The evidence for rimonabant in maintaining abstinence is inconclusive. Rimonabant 20 mg may moderate weight gain in the long term.

Nicotine receptor partial agonists for smoking cessation.

BACKGROUND: Nicotine receptor partial agonists may help smokers to quit by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). Varenicline was developed as a nicotine receptor partial agonist from cytisine, a drug widely used in central and eastern Europe for smoking cessation. The first trial reports of varenicline were released in 2006, and further trials are underway. OBJECTIVES: The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('varenicline' or 'cytisine' or 'Tabex' or 'nicotine receptor partial agonist') and 'smoking' in the title or abstract, or as keywords. We also searched MEDLINE, EMBASE, PsycINFO and CINAHL using MeSH terms and free text, and we contacted authors of trial reports for additional information where necessary. The last search was in October 2006. SELECTION CRITERIA: We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow up. The main outcome measured was abstinence from smoking after at least six months from the beginning of treatment. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we performed meta-analysis using the Mantel-Haenszel fixed-effect model. MAIN RESULTS: We found five trials of varenicline compared with placebo for smoking cessation; three of these also included a bupropion experimental arm. We also found one relapse prevention trial, comparing varenicline with placebo. The six trials covered 4924 participants, 2451 of whom used varenicline. We identified one trial of cytisine (Tabex) for inclusion. The pooled odds ratio (OR) for continuous abstinence at 12 months for varenicline versus placebo was 3.22 (95% confidence interval [CI] 2.43 to 4.27). The pooled OR for varenicline versus bupropion was 1.66 (95% CI 1.28 to 2.16). The main adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. The two trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated and effective during long-term use. The one cytisine trial included in this review found that more participants taking cytisine stopped smoking compared with placebo at two-year follow up, with an OR of 1.77 (95% CI 1.30 to 2.40). AUTHORS' CONCLUSIONS: Varenicline increased the odds of successful long-term smoking cessation approximately threefold compared with pharmacologically unassisted quit attempts. In trials reported so far, more participants quit successfully with varenicline than with bupropion. The effectiveness of varenicline as an aid to relapse prevention has not been clearly established. The main adverse effect of varenciline is nausea, but this is mostly at mild to moderate levels and tends to reduce with habituation. There is a need for independent trials of varenicline versus placebo, to test the early findings. There is also a need for direct comparisons with nicotine replacement therapy, and for further trials with bupropion, to establish the relative efficacy of the treatments.Cytisine may also increase the chances of quitting, but the evidence at present is inconclusive.

"Is this a dagger I see before me?"--an audit of stabbings and gunshot wounds in Limerick.

BACKGROUND: According to a recent study in Cardiff, the incidence of stab wounds is 14 per 100,000 population per annum. No such figures are available for Ireland. AIM: To evaluate the incidence, type of injury, medical consequences and outcome of patients with stab or gunshot wounds presenting to the Mid-Western Regional Hospital, Limerick, over a 12 month period. METHOD: A retrospective case study of all stab and gunshot wounds presenting over a 12 month period. RESULTS: Out of 62,000 new presentations to the Accident and Emergency (A&E) department, 101 (0.16%) were stabbings, giving an incidence of 33 per 100,000 population. Twenty-six patients required surgical intervention. There were three deaths. There were 10 gunshot wounds, of which 40% required surgical intervention, with no mortalities. CONCLUSION: The incidence of stab wounds presenting to our institution is high. Although constituting a small percentage of presentations to the A&E department they result in considerable morbidity and surgical activity.

Botulinum toxin type a for dysthyroid upper eyelid retraction.

PURPOSE: To evaluate the safety and efficacy of botulinum toxin type A for treatment of eyelid retraction resulting from thyroid eye disease (TED) during the inflammatory phase of the condition. METHODS: In this prospective, nonrandomized case series, 18 patients with inflammatory eyelid retraction caused by active TED received botulinum toxin type A injection (10, 5, or 2.5 U) for treatment of upper eyelid retraction. Botulinum toxin type A (Allergan, Irvine, CA, U.S.A.) was injected transconjunctivally just above the superior tarsal border in the elevator complex of the upper eyelid. RESULTS: Seventeen of 18 patients (94%) demonstrated a reduced marginal reflex distance (MRD1) after botulinum toxin injection. The average change in MRD1 of the treated eyelid after injection was -2.35 mm (range, 0 to -8.0 mm). Of the 27 eyelids injected, 33% had a 0- to 1-mm drop in eyelid height, 30% had a 1.5- to 2-mm decrease, 22% had a 2.5- to 3-mm decrease, and 15% had a greater than 3-mm decrease in eyelid height. None of the treated eyelids were noted to increase in height. One patient showed no alteration inafter treatment. One patient had clinically MRD1 significant ptosis and one patient reported worsening of preexisting diplopia after injection. Three patients undergoing unilateral injection had relative contralateral eyelid elevation. All untoward effects resolved spontaneously without sequelae. CONCLUSIONS: : Botulinum toxin type A may be used in the inflammatory stage of thyroid eye disease to improve upper eyelid retraction. Individual response to treatment is variable, but this modality should be considered as a temporizing measure until stability for surgery is reached.

Nasolacrimal obstruction secondary to I(131) therapy.

PURPOSE: To report the finding of nasolacrimal drainage system obstruction associated with I(131) therapy for thyroid carcinoma from an updated and expanded cohort. METHODS: Patients with a history of epithelial derived thyroid carcinoma who had tearing were offered referral for evaluation by an oculoplastic surgeon. Patients underwent nasolacrimal probing and irrigation procedures with localization of their nasolacrimal obstruction. Therapy for the site of obstruction was instituted. RESULTS: Clinically significant tearing was identified in 26 patients, all of whom had previously undergone I(131) therapy (n = 563). Nineteen patients were evaluated and confirmed to have nasolacrimal drainage system obstruction; 7 have yet to be formally evaluated. Areas of obstruction included nasolacrimal duct, common canaliculus, and, rarely, distal upper and lower canaliculi. Patients were treated with a variety of modalities including silicone intubation, balloon dacryoplasty, dacryocystorhinostomy, and conjunctival dacryocystorhinostomy. CONCLUSIONS: The use of I(131) for thyroid carcinoma is associated with a 3.4% incidence of documented nasolacrimal drainage obstruction and an overall 4.6% incidence of documented or suspected obstruction. The true incidence may be higher, since - I(131) treated individuals were neither systematically evaluated nor questioned about tearing. It has yet to be established if the obstructions result from local toxicity caused by the passive flow of radioactive iodine containing tears through these tissues or the active uptake and concentration of I(131) in lacrimal drainage system tissues through the sodium/iodide supporter.