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Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder caused by pathologic variants in CYP27A1 , a gene involved in bile acid synthesis. Impaired function in this gene leads to accumulation of plasma cholestanol (PC) in various tissues, often in early childhood, resulting in such clinical signs as infantile diarrhea, early-onset bilateral cataracts, and neurological deterioration. The current study aimed to identify cases of CTX in a population of patients with a greater CTX prevalence than the general population, to facilitate early diagnosis. Patients diagnosed with early-onset, apparently idiopathic, bilateral cataracts between the ages of 2 and 21 years were enrolled. Genetic testing of patients with elevated PC and urinary bile alcohol (UBA) levels was used to confirm CTX diagnosis and determine CTX prevalence. Of 426 patients who completed the study, 26 met genetic testing criteria (PC ≥ 0.4 mg/dL and positive UBA test), and 4 were confirmed to have CTX. Prevalence was found to be 0.9% in enrolled patients, and 15.4% in patients who met the criteria for genetic testing.▪ [ABSTRACT FROM AUTHOR]

To investigate the outcome of retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) compared with conventional RARP in the early learning curve. Consecutive patients with prostate cancer who underwent RS-RARP were included to compare against conventional RARP of the same period. Propensity-score matching was performed based on age, prostate size, nerve-sparing approach, and final pathological risk categories. All patients were re-admitted to undergo trial without Foley catheter from post-operative day 7–10. Clinical follow-up was performed with monitoring of continence (day 0, 3 months, and the latest continence during the study period) and surveillance of PSA level. Between July 2017 and August 2019, 24 consecutive patients received RS-RARP in our centre. Propensity score matching was performed with the best matched 24 controls receiving conventional RARP. Overall median follow-up duration was 15.5 months. A majority of the patients belonged to the intermediate-risk group, with most of them harbouring pT2 disease (RS-RARP: 87.5%; conventional RARP: 79.2%). More patients in RS-RARP group achieved day-0 continence (33.3% vs 0%, p = 0.002) and 3-month continence (66.7% vs 12.5%, p = 0.001). During the whole study period, more RS-RARP achieved continence with 0 pad (91.7% vs 66.7%, p = 0.033). The mean months to continence is shorter in RS-RARP group (4.0 months vs 13.6 months, p = 0.002). No statistically significant differences between the two groups with respect to surgical margins, post-operative PSA detection, and the use of adjuvant radiotherapy. RS-RARP showed better continence rates when compared to conventional RARP even during the learning curve phase. [ABSTRACT FROM AUTHOR]

To assess the utility of 3D, tablet-based, glasses-free Accurate STEReotest (ASTEROID) in children compared with the Titmus test. Children aged 5-13 years were enrolled in a single-center, nonrandomized, observational comparison study and analyzed by age (5-7 vs 8-13 years) and visual acuity (20/25 or better in both eyes vs abnormal). Each participant underwent both the ASTEROID and Titmus stereoacuity tests. Stereoacuity was defined as fine (≤60 arcsec), moderate (61–200 arcsec), coarse (201–1199 arcsec), or very coarse to nil (≥1200 arcsec). Agreement between the tests was assessed using a weighted kappa (κ) statistic based on all four categories. A total of 112 children were included: 28 aged 5-7 with normal visual acuity, 30 aged 5-7 with abnormal visual acuity, 34 aged 8-13 with normal visual acuity, and 20 aged 8-13 with abnormal visual acuity. Mean ASTEROID score was 688 ± 533 arcsec (range, 13–1200 arcsec). Agreement between ASTEROID and Titmus test scores for participants overall was moderate (κ = 0.52). By subgroup, agreement was fair for children 5-7 with abnormal visual acuity (κ = 0.31), moderate for children 5-7 with normal visual acuity (κ = 0.47) and children 8-13 with normal visual acuity (κ = 0.42), and substantial for children 8-13 with abnormal visual acuity (κ = 0.76). Where ASTEROID and Titmus score group varied, ASTEROID score was poorer in 94% (47/50) of cases. ASTEROID is a digital, tablet-based test that evaluates global stereopsis, does not require glasses, and provides a continuum of scores. Among children, ASTEROID has good agreement with the Titmus test; however, it may be more sensitive at detecting stereovision deficits. Further study is necessary to determine which test is more accurate. [ABSTRACT FROM AUTHOR]

It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC). We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs). Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m2) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I 2 = 0%) compared with normal BMI (18.5 to <25 kg/m2). Each 5 kg/m2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I 2 = 0%). Similarly, with each 5 kg/m2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I 2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I 2 = 0%). No associations were observed between measures of obesity and risk of UC. In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC. [ABSTRACT FROM AUTHOR]

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• Clinical development of Dato-DXd is ongoing in multiple solid tumor types. (76 characters) • Encouraging efficacy and manageable tolerability was shown in phase I evaluation. (83 characters) • ILD/pneumonitis, IRRs, oral mucositis/stomatitis, and OSEs are AESIs for Dato-DXd. (84 characters) • Management guidelines have been developed based on clinical trial experience. (79 characters) Antibody drug conjugates (ADCs) are an emerging class of treatments designed to improve efficacy and decrease toxicity compared with other systemic therapies through the selective delivery of cytotoxic agents to tumor cells. Datopotamab deruxtecan (Dato-DXd) is a novel ADC comprising a topoisomerase I inhibitor payload and a monoclonal antibody directed to trophoblast cell-surface antigen 2 (TROP2), a protein that is broadly expressed in several types of solid tumors. Dato-DXd is being investigated across multiple solid tumor indications. In the ongoing, first-in-human TROPION-PanTumor01 phase I study (ClinicalTrials.gov: NCT03401385), encouraging and durable antitumor activity and a manageable safety profile was demonstrated in patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR+/HER2– BC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC). Improved understanding of the adverse events (AEs) that are associated with Dato-DXd and their optimal management is essential to ensure safe and successful administration. Interstitial lung disease/pneumonitis, infusion-related reactions, oral mucositis/stomatitis, and ocular surface events have been identified as AEs of special interest (AESIs) for which appropriate prevention, monitoring, and management is essential. This article summarizes the incidence of AESIs among patients with HR+/HER2− BC, TNBC, and NSCLC reported in TROPION-PanTumor01. We report our recommendations for AESI prophylaxis, early detection, and management, using experience gained from treating AESIs that occur with Dato-DXd in clinical trials. [ABSTRACT FROM AUTHOR]

To assess corneal tomographic, topographic, and refractive changes in children with high astigmatism and their ability to exclude keratoconus. In this longitudinal observational study, the medical records of children with high regular cylindrical refraction of ≥3.50 D referred to the Hospital for Sick Children, Toronto, to exclude keratoconus between January 2009 and June 2020 were reviewed retrospectively. Corneal tomography records (Scheimpflug imaging) were reviewed for subjects with total astigmatism of ≥ +3.50 D by retinoscopy. Children with abnormal anterior segment examination and/or other risk factors for corneal disease or ectasia and those with unreliable corneal tomography were excluded. Baseline demographic, longitudinal tomographic, topographic, and refractive data were analyzed. A total of 67 eyes of 37 children (mean age, 9.1 ± 3.5 years) were included. Mean cylindrical refraction at presentation was 5.10 ± 1.30 D. Mean follow-up was 2.3 ± 1.8 years. Twenty-nine eyes had Kmax ≥47.20 D at baseline, with no change at last follow-up. Ksteep, Kmax, and thinnest pachymetry were 46.44 ± 2.33 D, 47.06 ± 2.57 D, and 525.86 ± 35.45 μm, respectively, at baseline compared with 46.40 ± 2.28 D, 46.98 ± 2.40 D, and 527.61 ± 37.67 μm at last follow-up (P > 0.05). All eyes were predicted as not having keratoconus using inferior-superior dioptric asymmetry ratio (I-S ratio), and the keratometry, inferior-superior, and astigmatism index (KISA%), which also incorporates skew percentage. The other tomographic indices predicted keratoconus or subclinical keratoconus in at least 22.4% of eyes. All parameters did not significantly change during follow-up. In the absence of other risk factors for keratoconus, children with high regular astigmatism demonstrated clinical and tomographic stability over time. Based on our results, we recommend that I-S ratio and KISA% be primarily used when monitoring normal children with high astigmatism to rule out keratoconus-related changes. [ABSTRACT FROM AUTHOR]

Several studies have been published on the association between food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC), with some variability in results. We performed a systematic literature review and meta-analysis to study this association. From PubMed, Medline, and Embase until October 2022, we identified cohort studies that studied the association between food processing and the risk of CD or UC. Risk of bias of the included studies was assessed by the Newcastle-Ottawa scale. We computed pooled hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects meta-analysis based on estimates and standard errors. A total of 1,068,425 participants were included (13,594,422 person-years) among 5 cohort studies published between 2020 and 2022. Four of the 5 included studies were scored as high quality. The average age of participants ranged from 43 to 56 years; 55%–83% were female. During follow-up, 916 participants developed CD, and 1934 developed UC. There was an increased risk for development of CD for participants with higher consumption of ultra-processed foods compared with those with lower consumption (HR, 1.71; 95% CI, 1.37–2.14; I2 = 0%) and a lower risk of CD for participants with higher consumption of unprocessed/minimally processed foods compared with those with lower consumption (HR, 0.71; 95% CI, 0.53–0.94; I2 = 11%). There was no association between risk of UC and ultra-processed foods (HR, 1.17; 95% CI, 0.86–1.61; I2 = 74%) or unprocessed/minimally processed foods (HR, 0.84; 95% CI, 0.68–1.02; I2 = 0%). Higher ultra-processed food and lower unprocessed/minimally processed food intakes are associated with higher risk of CD but not UC. [Display omitted] [ABSTRACT FROM AUTHOR]

Corneal cross-linking (CXL) is typically performed under topical anesthesia, which may be unsuitable in children and individuals with severe anxiety, poor cooperation, or neurodevelopmental issues. We describe a technique of CXL under general anesthesia that uses sevoflurane and propofol with laryngeal airway or nasal oxygen cannulas, and forceps or microsponges to stabilize the eye position intraoperatively. We also developed a simple and time-saving technique of bilateral simultaneous CXL, whereby the second eye can undergo CXL concurrently with the first in a staggered fashion. Using this technique, we have been able to eliminate up to 25% of surgical time required in standard bilateral procedures. Postoperatively, multimodal analgesia was administered to ensure patient comfort and prevent excessive eye rubbing. In total, 21 eyes of 13 subjects ≤18 years of age were treated. During a median follow-up of 14.5 months (range, 4-43), the only complication observed was sterile corneal infiltrate in 1 eye that resolved with a short course of corticosteroids. [ABSTRACT FROM AUTHOR]

Industrial foods have been associated with increased risks of several chronic conditions. We investigated the relationship between the degree of food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC) in the European Prospective Investigation into Cancer and Nutrition cohort. Analyses included 413,590 participants (68.6% women; mean baseline age, 51.7 y) from 8 European countries. Dietary data were collected at baseline from validated country-specific dietary questionnaires. Associations between proportions of unprocessed/minimally processed and ultraprocessed food intake and CD and UC risks were estimated using Cox models to obtain hazard ratios (HRs) and 95% CIs. Models were stratified by center, age, and sex, and adjusted for smoking status, body mass index, physical activity, energy intake, educational level, and alcohol consumption. During a mean follow-up period of 13.2 years, 179 incident cases of CD and 431 incident cases of UC were identified. The risk of CD was lower in people consuming high proportions of unprocessed/minimally processed foods (adjusted HR for the highest vs lowest quartile: 0.57; 95% CI, 0.35–0.93; P trend <.01), particularly fruits and vegetables (adjusted HRs, 0.54; 95% CI, 0.34–0.87 and 0.55; 95% CI, 0.34–0.91, respectively). There was no association between unprocessed/minimally processed food intake and the risk of UC. No association was detected between ultraprocessed food consumption and CD or UC risks. In the European Prospective Investigation into Cancer and Nutrition cohort, consumption of unprocessed/minimally processed foods was associated with a lower risk of CD. No association between UC risk and food processing was found. [Display omitted] [ABSTRACT FROM AUTHOR]

Background and Aims Current evidence of whether distal hyperplastic polyps (HPs) are markers of proximal neoplasia (PN) is mixed. We evaluated the association between distal neoplasia and synchronous PN in asymptomatic subjects. Methods We recruited 5819 Chinese asymptomatic screening participants 50 to 70 years of age who underwent colonoscopy in Hong Kong from 2008 to 2014, of whom 206 subjects with distal advanced neoplasia or cancer were excluded. The association between distal pathology (tubular adenomas [TAs], HPs, no polyps) and proximal pathology (PN, proximal advanced neoplasia [PAN]) was assessed by multivariate regression models, overall and stratified by the Asia Pacific Colorectal Screening scoring system (scores of 4-7, high risk; scores of 0-3, lower risk). Results The prevalence of PN in the no distal polyps group, distal HPs group, and distal TAs group was 14.8%, 19.3%, and 29.4%, respectively. The corresponding prevalence of PAN was 1.8%, 3.2%, and 3.5%. Participants with distal HPs did not have significantly higher odds of PN (adjusted odds ratio [AOR] 1.24; 95% confidence interval [CI], 0.97-1.59; P = .089), and their association with PAN was marginally significant (AOR 1.77; 95% CI, 1.00-3.13; P = .052), except in lower risk subjects for whom the odds of PAN were marginally higher in the distal HPs group than the no distal polyps group (AOR 1.97; 95% CI, 1.01-3.85; P = .048). Overall, the distal polyps group had significantly lower odds of PN than the distal TAs group (AOR 0.55; 95% CI, 0.40-0.76; P < .001). The increased risk of PN and PAN among those with distal HPs was modest. Conclusions A direct association between distal HPs and PN is lacking, and this implies a need for a multivariate assessment of the risk of PAN. Recommending colonoscopy for every patient with distal HPs detected by screening sigmoidoscopy is not supported by this study. [ABSTRACT FROM AUTHOR]

Background & Aims The risk of colorectal neoplasms among siblings of patients with advanced adenomas is not clear. We determined the prevalence of advanced adenomas in the siblings of patients with advanced adenomas and compared it with that of siblings of individuals without these lesions. Methods In a blinded, cross-sectional study, colonoscopies were performed (from 2010 through 2014), at 2 hospitals in Hong Kong on 200 asymptomatic siblings of patients with advanced adenomas (exposed; mean age, 58.2 ± 6.3 years; adenomas ≥10 mm, high-grade dysplasia, villous, or tubulovillous) and 400 age- and sex-matched siblings of subjects with normal findings from colonoscopies and no family history of colorectal cancer (unexposed; mean age, 58.1 ± 6 years). We recruited 1 sibling per family. The primary outcome was prevalence of advanced adenomas. Results Baseline demographics (ie, aspirin use, smoking, body mass index, and metabolic diseases) did not differ significantly between exposed and unexposed individuals. The prevalence of advanced adenoma was 11.5% among the exposed subjects and 2.5% among the unexposed subjects (matched odds ratio [mOR] = 6.05; 95% confidence interval [CI]: 2.74−13.36; P < .001). The prevalence of adenomas ≥10 mm was higher among exposed than unexposed siblings (10.5% vs 1.8%; mOR = 8.59; 95% CI: 3.44−21.45; P < .001), as was the prevalence of villous adenomas (5.5% vs 1.3% in unexposed; mOR = 6.28; 95% CI: 2.02−19.53; P = .001) and all colorectal adenomas (39.0% vs 19.0% in unexposed; mOR = 3.29; 95% CI: 2.16−5.03; P < .001). Two cancers were detected in exposed siblings and none in unexposed siblings. Conclusions In a cross-sectional study of subjects undergoing colonoscopy in Hong Kong, siblings of individuals with at least 1 advanced adenoma had a 6-fold increased odds of advanced adenoma compared with subjects who had a sibling with a screening colonoscopy with no identified neoplasia. ClinicalTrials.gov , Number: NCT01593098 . [ABSTRACT FROM AUTHOR]

To assess interdevice agreement between the iCare IC200 rebound tonometer and Perkins applanation tonometry (gold standard) in a healthy pediatric population. A total of 42 eyes of 42 healthy children were assessed using both tonometers. Data was collected on subject's age, sex, best-corrected visual acuity, and central corneal thickness (CCT). Intraclass correlation coefficient (ICC) and Bland-Altman analyses were used to determine agreement between IC200 and Perkins applanation tonometers. Linear regression analyzed the effects of intraocular pressure (IOP) on device difference. The mean age and standard deviation of healthy pediatric subjects was 10.0 ± 3.3 years. The mean difference between IC200 and Perkins tonometers (IC200-Perkins) was 0.72 mm Hg, with a mean of 17.1 ± 3.0 mm Hg and 16.4 ± 2.5 mm Hg, respectively. The absolute agreement, or ICC, between tonometers was 0.63 (95% CI, 0.56-0.70). Bland-Altman analysis showed 95% limits of agreement ranging from −5.2 to +6.6 mm Hg. CCT was not correlated with IOP for either the IC200 (P = 0.35) or the Perkins tonometer (P = 0.052). Compared to applanation tonometry, IC200 overestimated IOP in healthy children, with a greater frequency of readings > +2 mm Hg than < −2 mm Hg compared to Perkins. There was moderate agreement between tonometers. CCT was not found to influence IOP measurement for either tonometer. [ABSTRACT FROM AUTHOR]

Background & Aims We compared the accuracy of a qualitative fecal immunochemical test (FIT) in identifying patients with proximal vs distal advanced neoplasia and evaluated whether analysis of 2 specimens performed better than analysis of 1 specimen. Distal advanced neoplasia was defined as colorectal cancer (CRC), any colorectal adenoma ≥10 mm in diameter, high-grade dysplasia, or a lesion with villous or tubulovillous histologic characteristics in a location distal to the splenic flexure, including the descending colon, the rectosigmoid, and the rectum. Methods We collected data from 5343 subjects (50−70 years old) who received 2 FITs (Hemosure; cutoff value, 10 μg hemoglobin/g feces) before colonoscopy in an invitational CRC screening program in Hong Kong from 2008 through 2012. We calculated the FIT’s sensitivity, specificity, positive predictive value (PPV), and negative predictive value in detecting colorectal neoplasia. Results Of the participants, 13.6%, 12.2%, and 6.0% had distal, proximal, and synchronous distal or proximal neoplasia, respectively. Advanced neoplasia was detected in 291 subjects (5.4%); 22 (0.4%) had CRC. FIT detected distal advanced adenoma with 39.7% sensitivity (95% confidence interval [CI], 32.0%−48.0%) vs proximal advanced adenoma with 25.0% sensitivity (95% CI, 17.3%−34.6%; P = .014), distal advanced neoplasia with 40.0% sensitivity (95% CI, 32.5%−47.9%) vs proximal advanced neoplasia with 27.9% sensitivity (95% CI, 20.0%−37.4%; P = .039), and any distal adenoma ≥10 mm, irrespective of other lesion characteristics, with 39.5% sensitivity (95% CI, 31.0%−48.7%) vs proximal adenoma with 25.3% sensitivity (95% CI, 16.5%−36.6%; P = .038). The specificity of FIT in detecting CRC was similar between the proximal and distal colon. FIT detected distal lesions with higher PPV than proximal lesions. One FIT detected advanced neoplasia with 31.8% sensitivity (95% CI, 25.9%−38.4%) and 92.4% specificity (95% CI, 91.6%−93.2%), whereas 2 FITs detected advanced neoplasia with 34.1% sensitivity (95% CI, 28.0%−40.8%; P = .617) and 91.9% specificity (95% CI, 91.0%−92.7%; P = .327). FIT detected distal advanced neoplasia with greater sensitivity and higher PPV than proximal advanced neoplasia. Conclusions In an analysis of data from subjects who underwent CRC screening in Hong Kong, FIT detected distal advanced neoplasia with higher sensitivity than proximal advanced neoplasia. Analysis of 1 vs 2 specimens by FIT identified advanced neoplasia with similar test characteristics. [ABSTRACT FROM AUTHOR]

Background Certain subgroups have higher rates of false fecal immunochemical test (FIT) results, yet few studies have addressed this topic. Objective To identify demographic factors associated with false-positive and false-negative FIT results in colorectal cancer screening. Design Retrospective database review of prospectively collected data. Setting A bowel cancer screening center in Hong Kong invited participants for colorectal cancer screening (2008-2012). Patients Study participants who underwent both FIT and colonoscopy in the first year (n = 4482) and underwent colonoscopy after negative FIT results for 3 consecutive years (n = 857). Main Outcome Measurements The diagnostic accuracy and predictive values of FIT according to participant characteristics. Results The sensitivity, specificity, positive predictive values, and negative predictive values for advanced neoplasia were 33.1%, 91.9%, 19.0%, and 96.0%, respectively. Participants 66 to 70 years of age had higher sensitivity, whereas older age, smoking, and use of aspirin/nonsteroidal anti-inflammatory drugs were associated with lower specificity. The rates of false-positive and false-negative results were 8.1% and 66.9%, respectively. Older age (66-70 years; adjusted odds ratio [AOR] 1.95; 95% confidence interval [CI], 1.35-2.81; P < .001), smoking (AOR 1.68; 95% CI, 1.08-2.61; P = .020), and the presence of polypoid adenoma (AOR 1.71; 95% CI, 1.14-2.57; P = .009) were associated with false-positive results. Younger participants (AOR for elderly participants 0.31) and the use of aspirin/nonsteroidal anti-inflammatory drugs (AOR 4.44) in participants with 1 FIT with negative results and the absence of high-grade dysplasia (AOR for presence 0.41) were associated with false-negative results. Limitations Self-referred participants who received one type of qualitative FIT. Conclusion These findings could be used to target screening more toward those with a higher risk of false-negative results and those with a lower risk of false-positive results for earlier colonoscopy. [ABSTRACT FROM AUTHOR]

Background & Aims: Colorectal cancer (CRC) is the second-most common cancer in Hong Kong. Relatives of patients with CRC have an increased risk of colorectal neoplasm. We assessed the prevalence of advanced neoplasms among asymptomatic siblings of patients with CRC. Methods: Patients with CRC were identified from the Prince of Wales Hospital CRC Surgery Registry from 2001 to 2011. Colonoscopies were performed for 374 siblings of patients (age, 52.6 ± 7.4 y) and 374 age- and sex-matched siblings of healthy subjects who had normal colonoscopies and did not have a family history of CRC (controls, 52.7 ± 7.4 y). We identified individuals with advanced neoplasms (defined as cancers or adenomas of at least 10 mm in diameter, high-grade dysplasia, with villous or tubulovillous characteristics). Results: The prevalence of advanced neoplasms was 7.5% among siblings of patients and 2.9% among controls (matched odds ratio [mOR], 3.07; 95% confidence interval [CI], 1.5–6.3; P = .002). The prevalence of adenomas larger than 10 mm was higher among siblings of patients than in controls (5.9% vs 2.1%; mOR, 3.34; 95% CI, 1.45–7.66; P = .004), as was the presence of colorectal adenomas (31.0% vs 18.2%; mOR, 2.19; 95% CI, 1.52–3.17; P < .001). Six cancers were detected among siblings of patients; no cancers were detected in controls. The prevalence of advanced neoplasms among siblings of patients was higher when their index case was female (mOR, 4.95; 95% CI, 1.81–13.55) and had distally located CRC (mOR, 3.10; 95% CI, 1.34–7.14). Conclusions: In Hong Kong, siblings of patients with CRC have a higher prevalence of advanced neoplasms, including CRC, than siblings of healthy individuals. Screening is indicated in this high-risk population. ClinicalTrials.gov number: NCT00164944. [ABSTRACT FROM AUTHOR]

Background & Aims: Computed tomography colonography (CTC) is a recommended screening modality for colorectal cancer (CRC). It is not known whether polyps 6–9 mm based on CRC are likely to have advanced histologic features in Asian patients. We estimated the risk of advanced colonic neoplasia (ACN) from polyps <10 mm and the risk of ACN detection failure if patients with polyps <10 mm are not referred for colonoscopy. Methods: The study included 1457 subjects from the Asia-Pacific Working Group on CRC screening and the Hong Kong CRC screening program. Polyps and ACN found during colonoscopy examinations were classified by size and histology. Results: Of the subjects, 38.2% had polyps; 16.7% of these were ACN, 5.4% of ACN were ≤5 mm, and 24.7% of the ACN were 6–9 mm. Adopting the policy of reporting polyps found by CTC of <5 mm as normal and repeating CTC in patients with polyps of 6–9 mm, 5.4% of subjects with ACN, 4.5% of male subjects, and 11.5% of subjects with family history of CRC would be classified as normal. In referring patients with polyps of 6–9 mm for CTC surveillance, 20.4% of those with ACN, 22.4% of those that are male, and 23.1% of those with family histories of CRC would have polypectomies delayed by at least 3 years. Conclusions: A substantial proportion of polyps <10 mm have advanced histologic features in Asia, so patients with a polyp of 6 mm or more at CTC should be offered colonoscopies with polypectomies, rather than CTC surveillance of polyps. [Copyright &y& Elsevier]

Purpose: This prospective trial aimed to evaluate the safety and effectiveness of transarterial ethanol ablation (TEA) of intrahepatic lesions of hepatocellular carcinoma (HCC) with a Lipiodol–ethanol mixture. Materials and Methods: Seventy-seven patients were recruited and 164 lesions (mean size, 5.2 cm ± 3.0) were treated. Inclusion criteria included histologic proof of HCC, refusal of (n = 9) or contraindication to (n = 68) surgical resection, Eastern Cooperative Oncology Group performance status no greater than 2, and intrahepatic disease without vascular invasion. The mixture consisted of 33% ethanol by volume, with the total dose of Lipiodol–ethanol mixture limited to 60 mL for each treatment session. The primary endpoint was patient survival. Secondary endpoints were tumor response, adverse effects of treatment, and progression-free survival. Median follow-up time for the whole cohort was 2.3 years. Results: Median overall survival was 2.2 years. Overall survival and progression-free survival rates at 1 year and 2 years were 77.9% and 50.1% and 63.6% and 46.3%, respectively. Complete ablation according to radiologic criteria was achieved in 61 patients (79.2%) and 86% of the 164 treated lesions. Mean tumor volume reduction was 65.22%. Patient survival was significantly better in patients with tumors no larger than 5 cm (Cox proportional-hazards regression, P = .0074). Treatment response was significantly better for patients with tumors no greater than 7 cm (χ2 test, P = .0462; Fisher exact test, P = .0326). Adverse effects included irreversible hepatic decompensation (0.6% of procedures), pain (4.8%), and fever (13.8%). Conclusions: TEA is a safe and effective means to establish local control of unresectable and resectable intrahepatic lesions of HCC. [Copyright &y& Elsevier]

A coaxial technique was introduced for successful embolization of a large fusiform splenic artery aneurysm in a vessel with a large caliber and a great degree of tortuosity. A standard 5-F angioplasty catheter was placed at the immediate afferent artery for occlusion of arterial inflow into the aneurysm, thereby preventing intraaneurysmal hypertension during embolization of the efferent segment. This was followed by coaxial microcatheterization of the immediate efferent segment for coil embolization, and then embolization of the afferent segment. It is postulated that this approach may improve the safety of embolization of large aneurysms with unfavorable morphology by decreasing the pressure on the aneurysm just after closure of the efferent segment. [Copyright &y& Elsevier]

To evaluate structural features and visual outcomes in eyes with a prior history of laser treatment for retinopathy of prematurity (ROP). Laser-treated eyes for type 1 ROP, preterm monitored eyes, and full-term control eyes were included. LogMAR conversion of Snellen best-corrected visual acuity and spherical equivalent based on cycloplegic refraction were measured in children 5-15 years of age. Anterior segment optical coherence tomography (OCT) was used to study structural features, including anterior chamber angle (ACA) in a subset of eyes. A total of 50 eyes of 50 patients were included (19 full-term eyes, 19 laser-treated type 1 ROP eyes, 12 preterm monitored eyes). Of these, 44 eyes had visual outcomes data, and 15 eyes had anterior segment data. There was no significant difference in sex or age at final examination between the three groups. There was no significant difference in gestational age between the laser-treated and preterm monitored groups. Compared with the full-term control group and the preterm monitored group, the laser-treated ROP group had narrower ACA and more myopic refractive error. There was a significant correlation between ACA and spherical equivalent. Laser treatment may affect angle configuration in ROP eyes. Anterior segment OCT is an easy and useful modality that could aid in screening for visually impairing conditions such as myopia and glaucoma in children with ROP. [ABSTRACT FROM AUTHOR]

Ophthalmomyiasis interna posterior is a rare condition caused by the invasion of the ocular posterior segment by the larval form of certain flies in the order Diptera. The main clinical features are reduced visual acuity, intense posterior uveitis, and neuroretinitis. Treatment of this condition is predominantly surgical, including argon laser photocoagulation for subretinal larva and pars plana vitrectomy for intravitreal infection. We report a case of ophthalmomyiasis interna posterior in a 12-year-old girl that masqueraded as orbital cellulitis and was successfully treated with Nd:YAG laser photodisruption. [ABSTRACT FROM AUTHOR]

Background & Aims Many colorectal cancer (CRC) cells contain mutations in KRAS. Analyses of CRC cells with mutations in APC or CTNNB1 and KRAS identified SLC25A22 , which encodes mitochondrial glutamate transporter, as a synthetic lethal gene. We investigated the functions of SLC25A22 in CRC cells with mutations in KRAS. Methods We measured levels of SLC25A22 messenger RNA and protein in paired tumor and nontumor colon tissues collected from 130 patients in Hong Kong and 17 patients in China and compared protein levels with patient survival times. Expression of SLC25A22 was knocked down in KRAS mutant CRC cell lines (DLD1, HCT116, LOVO, SW480, SW620, and SW1116) and CRC cell lines without mutations in KRAS (CACO-2, COLO205, HT29, and SW48); cells were analyzed for colony formation, proliferation, glutaminolysis and aspartate synthesis, and apoptosis in Matrigel and polymerase chain reaction array analyses. DLD1 and HCT116 cells with SLC25A22 knockdown were grown as xenograft tumors in nude mice; tumor growth and metastasis were measured. SLC25A22 was expressed ectopically in HCT116 cells, which were analyzed in vitro and grown as xenograft tumors in nude mice. Results Levels of SLC25A22 messenger RNA and protein were increased in colorectal tumor tissues compared with matched nontumor colon tissues; increased protein levels were associated with shorter survival times of patients ( P = .01). Knockdown of SLC25A22 in KRAS mutant CRC cells reduced their proliferation, migration, and invasion in vitro, and tumor formation and metastasis in mice, compared with cells without SLC25A22 knockdown. Knockdown of SLC25A22 reduced aspartate biosynthesis, leading to apoptosis, decreased cell proliferation in KRAS mutant CRC cells. Incubation of KRAS mutant CRC cells with knockdown of SLC25A22 with aspartate increased proliferation and reduced apoptosis, which required GOT1, indicating that oxaloacetate is required for cell survival. Decreased levels of oxaloacetate in cells with knockdown of SLC25A22 reduced regeneration of oxidized nicotinamide adenine dinucleotide and reduced nicotinamide adenine dinucleotide phosphate. Reduced oxidized nicotinamide adenine dinucleotide inhibited glycolysis and decreased levels of adenosine triphosphate, which inactivated mitogen-activated protein kinase kinase and extracellular signal–regulated kinase signaling via activation of AMP-activated protein kinase. An increased ratio of oxidized nicotinamide adenine dinucleotide phosphate to reduced nicotinamide adenine dinucleotide phosphate induced oxidative stress and glutathione oxidation, which suppressed cell proliferation. Asparagine synthetase mediated synthesis of asparagine from aspartate to promote cell migration. Conclusions SLC25A22 promotes proliferation and migration of CRC cells with mutations KRAS, and formation and metastasis of CRC xenograft tumors in mice. Patients with colorectal tumors that express increased levels of SLC25A22 have shorter survival times than patients whose tumors have lower levels. SLC25A22 induces intracellular synthesis of aspartate, activation of mitogen-activated protein kinase kinase and extracellular signal–regulated kinase signaling and reduces oxidative stress. [ABSTRACT FROM AUTHOR]

Background & Aims Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), commonly prescribed in the primary and secondary prevention of cardiovascular disease, promote apoptosis and limit proliferation of esophageal cancer cell lines. We investigated whether statin use after a diagnosis of esophageal cancer is associated with reduced esophageal cancer–specific and all-cause mortality. Methods We identified a cohort of 4445 men and women in the United Kingdom diagnosed with esophageal cancer from January 2000 through November 2009 using the General Practice Research Database. The National Cancer Registry and Office of National Statistics datasets established the histologic subtype and cancer-specific mortality, respectively. Cox proportional hazard regression analysis with time-dependent exposures estimated the association between statin use after diagnosis and esophageal cancer–specific and all-cause mortality. Results The median survival time of the entire cohort was 9.2 months (interquartile range [IQR], 3.7–23.2 mo). Among subjects who used statins after a diagnosis of esophageal cancer, the median survival time was 14.9 months (IQR, 7.1–52.3 mo) compared with 8.1 months for nonusers (IQR, 3.3–20 mo). In the entire cohort, statin use after diagnosis was associated with a decreased risk of esophageal cancer–specific mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.44–0.86) and all-cause mortality (HR, 0.67; 95% CI, 0.58–0.77). In patients with esophageal adenocarcinoma, statin use after diagnosis was associated with a decreased risk of esophageal cancer–specific mortality (HR, 0.61; 95% CI 0.38–0.96) and all-cause mortality (HR, 0.63; 95% 0.43–0.92). This effect was not observed in patients with esophageal squamous cell carcinoma. There was no evidence for effect modification of these associations with statin use before the cancer diagnosis. Conclusions In a large population-based cohort, statin use after a diagnosis of esophageal adenocarcinoma, but not esophageal squamous cell carcinoma, was associated with reduced esophageal cancer–specific and all-cause mortality. [ABSTRACT FROM AUTHOR]

Background & Aims: We investigated the efficacy of electroacupuncture in reducing the duration of postoperative ileus and hospital stay after laparoscopic surgery for colorectal cancer. Methods: We performed a prospective study of 165 patients undergoing elective laparoscopic surgery for colonic and upper rectal cancer, enrolled from October 2008 to October 2010. Patients were assigned randomly to groups that received electroacupuncture (n = 55) or sham acupuncture (n = 55), once daily from postoperative days 1–4, or no acupuncture (n = 55). The acupoints Zusanli, Sanyinjiao, Hegu, and Zhigou were used. The primary outcome was time to defecation. Secondary outcomes included postoperative analgesic requirement, time to ambulation, and length of hospital stay. Results: Patients who received electroacupuncture had a shorter time to defecation than patients who received no acupuncture (85.9 ± 36.1 vs 122.1 ± 53.5 h; P < .001) and length of hospital stay (6.5 ± 2.2 vs 8.5 ± 4.8 days; P = .007). Patients who received electroacupuncture also had a shorter time to defecation than patients who received sham acupuncture (85.9 ± 36.1 vs 107.5 ± 46.2 h; P = .007). Electroacupuncture was more effective than no or sham acupuncture in reducing postoperative analgesic requirement and time to ambulation. In multiple linear regression analysis, an absence of complications and electroacupuncture were associated with a shorter duration of postoperative ileus and hospital stay after the surgery. Conclusions: In a clinical trial, electroacupuncture reduced the duration of postoperative ileus, time to ambulation, and postoperative analgesic requirement, compared with no or sham acupuncture, after laparoscopic surgery for colorectal cancer. ClinicalTrials.gov number, NCT00464425. [Copyright &y& Elsevier]