Mutation and Methylation Analysis of the Chromodomain-Helicase-DNA Binding 5 Gene in Ovarian Cancer

Chromodomain, helicase, DNA binding 5 (CHD5) is a member of a subclass of the chromatin remodeling Swi/Snf proteins and has recently been proposed as a tumor suppressor in a diverse range of human cancers. We analyzed all 41 coding exons of CHD5 for somatic mutations in 123 primary ovarian cancers as well as 60 primary breast cancers using high-resolution melt analysis. We also examined methylation of the CHD5 promoter in 48 ovarian cancer samples by methylation-specific single-stranded conformation polymorphism and bisulfite sequencing. In contrast to previous studies, no mutations were identified in the breast cancers, but somatic heterozygous missense mutations were identified in 3 of 123 ovarian cancers. We identified promoter methylation in 3 of 45 samples with normal CHD5 and in 2 of 3 samples with CHD5 mutation, suggesting these tumors may have biallelic inactivation of CHD5. Hemizygous copy number loss at CHD5 occurred in 6 of 85 samples as assessed by single nucleotide polymorphism array. Tumors with CHD5 mutation or methylation were more likely to have mutation of KRAS or BRAF (P = .04). The aggregate frequency of CHD5 haploinsufficiency or inactivation is 16.2% in ovarian cancer. Thus, CHD5 may play a role as a tumor suppressor gene in ovarian cancer; however, it is likely that there is another target of the frequent copy number neutral loss of heterozygosity observed at 1p36.     

Tracheal carcinoma presenting as a thyroid cyst

A patient was seen with a thyroid cyst. Fine- and core-needle biopsies revealed no evidence of tumor. A thyroid cyst lined by malignant squamous cells was found at surgery. Invasive squamous carcinoma was found to arise in adjacent trachea. The thyroid gland was normal except for inflammatory changes. Aspiration biopsies of thyroid cysts may be misleading, especially when hemorrhagic; sclerosis should be performed with caution.     

Corneal triple procedure: indications, complications, and outcomes: a developing country scenario

PURPOSE: We report the indications, complications, and outcomes of 104 corneal triple procedures in our institute. METHODS: Patient records of 104 consecutive cases of corneal triple procedure (penetrating keratoplasty with extracapsular cataract extraction and intraocular lens implantation) performed by experienced corneal surgeons between January 1992 and December 1997 were retrospectively reviewed. Relevant preoperative, operative, and postoperative data were collected. The outcome was assessed by the graft clarity and visual acuity at the last visit. Survival analysis of these grafts was determined by Kaplan-Meier method. RESULTS: Of 104 patients, 70 were men and 34 were women. Mean age of these patients was 48.5+/-17.1 years (range, 1-75 years). Corneal scarring with cataract was the reason for surgery in 69 (66.4%) cases. The intraoperative complications included vitreous upthrust in seven (6.9%) cases and posterior capsular dehiscence in three (2.9%) cases. The most common early postoperative complications were increased intraocular pressure in 19 (18.3%) and increased anterior chamber reaction in 25 (24%) cases. Posterior capsular opacification was seen in 26 (25%), graft reaction in 15 (14.4%), and secondary glaucoma in 15 (14.4%) cases. These formed the important late postoperative complications. The average postoperative follow-up was 23.7+/-17.6 months (range, 1.6-79.4 months); at which time 72% of the grafts remained clear. At last follow-up, 40% of patients had a visual acuity of > or = 20/40. CONCLUSIONS: Corneal scarring with cataract is the most common reason for triple procedure in this part of the world. This is a safe surgical procedure with good graft clarity and reasonable visual recovery.     

Conjunctival intraepithelial neoplasia presenting as corneal ulcer

PURPOSE: To report a case of conjunctival intraepithelial neoplasia presenting as corneal ulcer. METHOD: Case report of a 28-year-old man who presented with sudden onset of pain, redness, and watering in the right eye. Examination of right cornea revealed deep stromal infiltrate inferonasally. Adjacent to the infiltrate and straddling the inferonasal limbus, a reddish well-defined sessible lesion with prominent blood vessels was seen. After corneal scraping for microbiological evaluation, the patient was treated with frequent instillation of ciprofloxacin hydrochloride 0.3% eyedrops. RESULTS: Corneal scraping revealed no microorganisms. Infiltrate resolved promptly after excision of the lesion. Histopathologic evaluation of the excised lesion revealed conjunctival intraepithelial neoplasia. CONCLUSIONS: This case highlights the fact that conjunctival intraepithelial neoplasia at the limbus may present as corneal ulcer. This ulcer could have occurred secondary to a dellen formation and epithelial breakdown predisposing to a corneal ulcer.     

Intravitreal pefloxacin therapy in postoperative endophthalmitis

Purpose : To study the efficacy of intravitreal pefloxacin in the management of suspected bacterial endophthalmitis. Methods : Twenty eyes with suspected postoperative bacterial endophthalmitis were given an intravitreal injection of pefloxacin (200 μg in 0.1 mL). If required the injection was repeated after 24 h. The main parameters evaluated were visual acuity, response to intravitreal therapy and any complications due to intravitreal pefloxacin. Results : Fourteen eyes (70%) responded to intravitreal pefloxacin therapy alone, while an additional pars plana vitrectomy was required in six eyes (30%). Nineteen eyes retained a visual acuity of 6/60 or better at 3 months after the initiation of therapy. A retinal detachment developed in one of the eyes which received intravitreal therapy. Conclusions : Intravitreal pefloxacin may be a useful alternative therapy in bacterial endophthalmitis.     

Complications of laser-in-situ-keratomileusis

Laser-in-situ-keratomileusis (LASIK) has become a popular technique of refractive surgery because of lower postoperative discomfort, early visual rehabilitation and decreased postoperative haze. Compared to photorefractive keratectomy (PRK), LASIK involves an additional procedure of creating a corneal flap. This may result in complications related to the flap, interface and underlying stromal bed. The common flap-related complications include thin flap, button holing, free caps, flap dislocation and flap striae. The interface complications of diffuse lamellar keratitis, epithelial ingrowth and microbial keratitis are potentially sight threatening. Compared to PRK, there is less inflammation and faster healing after LASIK, but there is a longer period of sensory denervation leading to the complication of dry eyes. The refractive complications include undercorrection, regression, irregular astigmatism, decentration and visual aberrations. Honest and unbiased reporting is important to understand the aetiology and redefine the management.     

Invasive aspergillosis in cancer

Ten confirmed cases of invasive aspergillosis (IA) in cancer patients were analysed retrospectively. Eight were pulmonary, one was sinonasal and one was cutaneous. The majority of patients had haematological malignancies (7), the remaining three were cases of solid tumours. Fever was present in all 10 cases. Cough and lung signs were present in all eight cases of invasive pulmonary aspergillosis. Haemoptysis was encountered in three of nine cases of pulmonary and sinonasal aspergillosis. Mortality was low (2%). While corticosteroids, antibiotics and anticancer chemotherapy/radiotherapy were factors predisposing the patients to IA, neutropenia was perhaps responsible for their mortality. Seven of the patients had other associated pathogens isolated in culture in addition to Aspergillus spp. Aspergillus fumigatus was the predominant species, followed by A. flavus, A. glaucus, A. nidulans and A. niger. Direct microscopic examination (in six of seven cases) and culture (six of seven cases) correlated well with radiographic and clinical findings in cases with lung involvement. Serology for anti-Aspergillus antibodies performed by gel diffusion precipitin test was positive in one case of sinonasal aspergillosis, wherein only one precipitin band was observed. Correlation of clinical symptoms, consistent radiographic findings and microbiological work-up (the latter including a triad of direct microscopy, culture and serology) are required to arrive at a diagnosis of IA, especially where histology cannot form the mainstay of diagnosis.     

Translation of microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and mesothelioma

The pathological distinction between malignant pleural mesothelioma (MPM)and adenocarcinoma (ADCA) of the lung can be cumbersome using established methods. We propose that a simple technique, based on the expression levels of a small number of genes, can be useful in the early and accurate diagnosis of MPM and lung cancer. This method is designed to accurately distinguish between genetically disparate tissues using gene expression ratios and rationally chosen thresholds. Here we have tested the fidelity of ratio-based diagnosis in differentiating between MPM and lung cancer in 181 tissue samples (31 MPM and 150 ADCA). A training set of 32 samples (16 MPM and 16 ADCA) was used to identify pairs of genes with highly significant, inversely correlated expression levels to form a total of 15 diagnostic ratios using expression profiling data. Any single ratio of the 15 examined was at least 90% accurate in predicting diagnosis for the remaining 149 samples (e.g., test set). We then examined (in the test set) the accuracy of multiple ratios combined to form a simple diagnostic tool. Using two and three expression ratios, we found that the differential diagnoses of MPM and lung ADCA were 95% and 99% accurate, respectively. We propose that using gene expression ratios is an accurate and inexpensive technique with direct clinical applicability for distinguishing between MPM and lung cancer. Furthermore, we provide evidence suggesting that this technique can be equally accurate in other clinical scenarios.     

Estimation of the effect of food on the disposition of oral 5-fluorouracil in combination with eniluracil

AIMS: To determine the effect of food on the pharmacokinetics of 5-fluoruracil (5-FU) taken orally with eniluracil and to compare the performance of different pharmacokinetic analysis methods in the detection a potential food-drug interaction. METHODS: In a randomized, open-label, two-way crossover study, 12 patients received eniluracil (50 mg, orally) on days 1 and 2 and 5-FU (20 mg/m(2), orally) on day 2 following either a 2-h fast or 20 min after a standard meal. Treatments were separated by 7 days. Timed blood samples were collected during the first two treatment periods and 5-FU concentrations determined by GC/MS. Data were analyzed and pharmacokinetic parameter estimates were obtained using a noncompartmental, two-stage and population analysis methods. RESULTS: In fasted individuals, the clearance/bioavailability of 5-FU was estimated to be 5.6 l/h. The mean absorption lag-time was 0.24 h and was followed by rapid absorption of 5-FU. Administration of 5-FU and eniluracil with food resulted in a decrease in the 5-FU absorption rate constant by 90%. As a result, the peak plasma concentration (C(max)) of 5-FU was decreased by 21% and the time to C(max) was increased 2.9-fold. Clearance of 5-FU, relative bioavailability, and area under the plasma concentration vs time curve (AUC) remained unchanged with coadministration of food. Similar results were obtained using all three data analysis methods. CONCLUSIONS: Administration of food with oral 5-FU and eniluracil slowed absorption of 5-FU and decreased 5-FU C(max), but did not effect AUC. Further investigation of the incorporation of population pharmacokinetic approaches in food effect studies is warranted.