BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a long half-life of 5-10 years in human beings as a result of its high lipophilicity, and little or no metabolism. We monitored TCDD, its form, distribution, and elimination in Victor Yushchenko after he presented with severe poisoning. METHODS: In late December, 2004, a patient presented with TCDD poisoning; the levels in his blood serum (108000 pg/g lipid weight) were more than 50 000-fold greater than those in the general population. We identified TCDD and its metabolites, and monitored their levels for 3 years using gas chromatography and high-resolution mass spectrometry in samples of blood serum, adipose tissue, faeces, skin, urine, and sweat, after they were extracted and cleaned with different organic solvents. FINDINGS: The amount of unmodified TCDD in the samples that were analysed accounted for about 60% of TCDD eliminated from the body during the same period. Two TCDD metabolites-2,3,7-trichloro-8-hydroxydibenzo-p-dioxin and 1,3,7,8-tetrachloro-2-hydroxydibenzo-p-dioxin-were identified in the faeces, blood serum, and urine. The faeces contained the highest concentration of TCDD metabolites, and were the main route of elimination. Altogether, the different routes of elimination of TCDD and its metabolites accounted for 98% of the loss of the toxin from the body. The half-life of TCDD in our patient was 15.4 months. INTERPRETATION: This case of poisoning with TCDD suggests that the design of methods for routine assessment of TCDD metabolites in human beings should be a main aim of TCDD research in the metabolomic era. FUNDING: University of Geneva Dermatology Fund, and Swiss Centre for Applied Human Toxicology.
Comment In: Lancet. 2009 Oct 3;374(9696):1131-219660808
A multidisciplinary nonmelanoma skin cancer (NMSC) clinic is held weekly at our center, where all new patients are jointly assessed by dermatology/dermatopathology, radiation oncology, and plastic surgery. A new patient database was established in 2004. The purpose of this study was to provide a preliminary report on the patients seen in the NMSC clinic and the treatment recommendations rendered.
The new patient database was reviewed from January 2004 to December 2008, and patient demographics, tumor characteristics, and treatment recommendations were extracted. Cochran-Mantel-Harnszel (CMH) testing and chi-square analysis were used to detect any associations or relationships between variables within the database. A p value of less than .05 was considered significant.
During the 5-year study period, 2,146 new patients were seen in the NMSC clinic. The majority of patients presented with basal cell carcinoma (64%) or squamous cell carcinoma (22%), with a median tumor size of 1 to 2 cm (range 0 to > 9 cm). Tumors were located in the head and neck region (80%), extremities (14%), and torso (6%). Previous treatment included biopsy only (62%), surgery (20%), electrodesiccation and curettage (11%), topical imiquimod (3%), and radiotherapy (1%). Treatment recommendations included surgery (55%) (with either simple excision [31%] or excision with margin control under frozen-section guidance [24%]), radiotherapy (19%), topical imiquimod (10%), observation (7%), and electrodesiccation and curettage (4%).
The NMSC clinic at our center sees a high volume of patients who benefit from the multidisciplinary assessment provided. Treatment recommendations were based on patient and disease characteristics as well as patient preference.
Lower duodenal biopsies (LDB) are not taken at every oesophago-gastro-duodenoscopy (EGD). In the present study, biopsies from the endoscopic normal lower duodenum were checked as a measure of quality assurance. From 1996 to 2000, 9,955 EGD were performed and 4,199 LDB were taken (42.2 %). Of these, 667 showed pathological histology (15.9 %). A non-specific inflammation was seen in 537 cases and lymphangiectasia in 30 cases. Signs of indigenous sprue were described histologically in 6 LDB. In 4 of the 6 first diagnoses, the LDB was taken owing to clinical suspicion of malabsorption syndrome. Giardia lamblia could be detected in 22 patients. Only 6 of the 22 patients had diarrhoea. A total of 18 clinically relevant first diagnoses were made by LDB in asymptomatic patients with normal endoscopic findings in the duodenum. In order to make a relevant first diagnosis, 233 LDB had to be taken. LDB can be dispensed within EGD when there is neither diarrhoea nor loss of weight, and no anemia, iron deficiency, vitamin deficiency, macrocytosis, hypoproteinaemia, meteorism, joint symptoms or fever.
OBJECTIVE: We evaluated the usefulness of contrast-enhanced harmonic gray scale sonography with a newly developed sonographic contrast medium as a means of guidance for percutaneous ablation therapy of hepatocellular carcinoma lesions not detected by conventional sonography. METHODS: We examined 85 patients with 108 hepatocellular carcinoma lesions that were identified as hypervascular by multidetector-row computed tomography by using contrast-enhanced harmonic gray scale sonography after injection of Sonazoid (GE Healthcare, Oslo, Norway), a lipid-stabilized suspension of a perfluorobutane gas microbubble contrast agent. We scanned the whole liver by this modality at a low mechanical index in the late phase to detect lesions not detected by conventional sonography and then scanned the lesions again by this modality at a high mechanical index to visualize tumor vessels and enhancement. We also performed percutaneous ablation therapy guided by this modality to treat viable hepatocellular carcinoma lesions that could not be detected by conventional sonography. RESULTS: Conventional sonography identified 90 (83%) of 108 hepatocellular carcinoma lesions; 15 (14%) additional viable lesions not detected by conventional sonography were detected in the late phase of contrast-enhanced harmonic gray scale sonography at a low mechanical index, and tumor vessels and enhancement were observed in the late phase at a high mechanical index. Contrast-enhanced harmonic gray scale sonography diagnosed 105 (97%) of the 108 viable hepatocellular carcinoma lesions, and 14 (93%) of the 15 lesions not detected by conventional sonography were successfully treated by percutaneous ablation therapy guided by this modality. CONCLUSIONS: Contrast-enhanced harmonic gray scale sonography is useful for guidance of percutaneous ablation therapy of hepatocellular carcinoma lesions not detected by conventional sonography.
Mutations of the tumor-suppressor gene p53 are common in epithelial tumors. Clonal mutations of p53 have been found in cervical and vulvar carcinomas negative for human papillomavirus (HPV), though at least in cervical cancer HPV infection and p53 mutations are not mutually exclusive. We have previously shown that about 40% of male genital warts and bowenoid papulosis lesions exhibit immunohistochemically detectable aberrant p53 protein, irrespective of the presence of HPV DNA. We studied p53 mutations in exons 4-8 with SSCP and sequencing in 13 male patients with 1 to 3 therapy-resistant genital warts or intra-epithelial neoplasias each and in 4 patients with penile squamous cell carcinoma. Thus, 13 genital warts, 6 bowenoid papulosis, 1 Queyrat's erythroplasia and 1 carcinoma in situ were studied. p53 protein was detected immunohistochemically, and HPV status was analyzed with DNA in situ hybridization and amplification of HPV-specific DNA. There was no correlation between p53 protein expression and HPV status. No mutations in exons 5-8 of the p53 gene were found in any of the lesions, and furthermore, no exon 4 mutations were found in lesions positive in p53 immunohistochemistry. In conclusion, overexpression of p53 does not indicate a p53 mutation in male genital warts, pre-malignant lesions or malignant squamous cell carcinomas. Our study thus suggests that p53 mutations are not important, or at least not early, events in male genital carcinogenesis.
Eight patients with Acanthamoeba keratitis were diagnosed and treated at our clinic between February 1991 and February 1993. Five of these were contact lens wearers, two had suffered recent corneal trauma and one had recently undergone penetrating keratoplasty. The diagnoses were based on both culture and histological examination of biopsy material in three cases, on culture alone in two cases and on histological examination alone in three cases. In all but one primary treatment was Propamidine isethionate and Neomycin/Polymyxin B topically and Ketoconazole orally. Because of poor healing three patients additionally received Paromomycin and Miconazole or Clotrimazol topically; two of these were further treated with Polyhexamethylene biguanide topically. The interval from initial symptoms to accurate diagnoses varied from one to eleven months. In one patient the eye could not be saved; in the remaining patients visual acuity after healing ranged from hand movements to 1.0.
In a Swedish celiac disease screening study (Exploring the Iceberg of Celiacs in Sweden), we systematically reviewed the clinical diagnostic procedures with the aim to evaluate the diagnostic accuracy and to take advantage of lessons learned for improving diagnostic routines.
A school-based celiac disease screening study involving 5 Swedish centers, with 10,041 invited 12-year-olds with 7567 consenting participation. All 192 children with elevated serological markers were recommended to undergo small-bowel biopsy, performed and evaluated according to local clinical routines. All of the mucosal specimens were reevaluated by 1 and, when needed, 2 expert pathologists to reach diagnostic consensus.
Small-bowel biopsies were performed in 184 children: 130 by endoscopy and 54 by suction capsule. Endoscopic biopsies were inconclusive in 0.6%, compared with 7.4% of biopsies by suction capsule. A patchy enteropathy was found in 9.1%. Reevaluation by the expert pathologist resulted in 6 additional cases with celiac disease and 1 cleared. Sixteen children with normal or inconclusive biopsies, 4 after endoscopy, and 12 after suction capsule were endoscopically rebiopsied, resulting in another 8 cases. The celiac disease prevalence of 30 of 1000 (95% confidence interval 26-34) was not statistically different from that previously reported.
The present review revealed the importance of controlling each step of the diagnostic procedure. Several cases would have been missed by relying only on local routines. To improve the quality of childhood celiac disease diagnostics, we recommend multiple endoscopic biopsies from both proximal and distal duodenum and standardized evaluation by a pathologist with good knowledge of celiac disease.
We reviewed the results of fine needle biopsy of the adrenal glands guided by ultrasonography or CT in 56 patients. The final diagnoses, obtained at operation, autopsy or follow-up were: metastasis (n = 22), adenoma (n = 21), adrenal cyst (n = 6), hematoma (n = 3), lymphoma (n = 1), pheochromocytoma (n = 1), lymph node (n = 1), and amyloid mass (n = 1). Sufficient cytologic material was obtained in 96.4% (54/56). The overall accuracy to differentiate benign from malignant disease was 85.7% (48/56), 2 were false-negative, one was false-positive. The biopsy was inconclusive ("possibly malignant") in 3 patients, 2 of whom had an additional cutting needle biopsy yielding a correct positive finding. No complications occurred. We conclude that in disseminated malignant disease with suspected adrenal metastases diagnostic results can be obtained with guided fine needle biopsy. Biopsy in primary adrenal lesions is helpful, especially if the aspirate of the lesion turns out to be composed of something other than adrenal cells.
The aim of this study was to determine the accuracy and clinical utility of fine needle aspiration (FNA) for the preoperative diagnosis of patients presenting with solitary thyroid nodules. Between 1987 and 1991, 317 patients with a thyroid nodule underwent FNA. Surgery was performed on 98 of the patients, and the cytologic findings were correlated with the final histologic diagnoses for these cases. Of the 98 patients operated on, satisfactory aspirates were obtained in 85 patients and classified as either malignant, suspicious for malignancy, or benign. The FNA was correct in predicting malignancy in 29 of 35 nodules (82.9%). With the benign nodules, FNA was correct in 44 of 50 nodules (88%). The overall accuracy of FNA was 85.9%. The accuracy for the combination of FNA and frozen section (FS) was 92.6%. We conclude that both FNA and FS are accurate tests that play a useful role in the pre- and intraoperative diagnostic evaluation of patients presenting with solitary thyroid nodules.