Sentinel node biopsy in papillary thyroid cancer--what is the potential?

PURPOSE: Sentinel node biopsy (SNB) may identify lymph node metastases in patients with papillary thyroid cancer (PTC), enabling selective application of central node dissection (CND). The aim of this study was to assess the feasibility of implementing SNB in patients undergoing thyroidectomy for a cytologically indeterminate/suspicious/malignant thyroid nodule and to determine the potential improvement in clinical outcomes and the costs associated with the SNB technique. METHODS: The treatment strategies and clinical and pathological outcomes of two retrospective cohorts of patients who underwent preoperative thyroid FNA over a 5-year period in two different centres were studied. The potential for implementing the SNB technique and the benefits and costs associated with implementation were estimated. RESULTS: In centre 1, in 819 adult patients who had thyroid fine-needle aspiration cytology, the final cytology was indeterminate, suspicious and diagnostic of malignancy in 113, 29 and 28 patients, respectively. One hundred eight patients were 'suitable' for SNB. Twenty-three of these patients had PTC, six of whom underwent CND. Of these six patients, node metastasis was absent in five--the cohort in whom prophylactic CND may have been avoided consequent to a negative 'sentinel node' biopsy. Morbidity attributable to CND may have been avoided in up to four patients over a 5-year period. Costs associated with implementation of SNB outweighed any potential savings. Analysis of 491 patients in centre 2 confirmed that the benefit of SNB in PTC was similarly limited; morbidity attributable to CND may have been avoided in up to seven patients over a 5-year period. CONCLUSIONS: Even under ideal conditions (assuming 100 % node identification rate and 0 % false negative rate), the potential short- to medium-term benefit of sentinel node biopsy in patients with thyroid cancer in centres implementing a policy of selective or routine prophylactic CND is low.

Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies.

BACKGROUND: Data on the long-term impact of SARS-CoV-2 infection in children and young people (CYP) are conflicting. We assessed evidence on long-term post-COVID symptoms in CYP examining prevalence, risk factors, type and duration. METHODS: Systematic search of published and unpublished literature using 13 online databases between 01/12/2019 and 31/07/2021. Eligible studies reported CYP ≤19 years with confirmed or probable SARS-CoV-2 with any symptoms persisting beyond acute illness. Random effects meta-analyses estimated pooled risk difference in symptom prevalence (controlled studies only) and pooled prevalence (uncontrolled studies also included). Meta-regression examined study characteristics hypothesised to be associated with symptom prevalence. Prospectively registered: CRD42021233153. FINDINGS: Twenty two of 3357 unique studies were eligible, including 23,141 CYP. Median duration of follow-up was 125 days (IQR 99-231). Pooled risk difference in post-COVID cases compared to controls (5 studies) were significantly higher for cognitive difficulties (3% (95% CI 1, 4)), headache (5% (1, 8)), loss of smell (8%, (2, 15)), sore throat (2% (1, 2)) and sore eyes (2% (1, 3)) but not abdominal pain, cough, fatigue, myalgia, insomnia, diarrhoea, fever, dizziness or dyspnoea. Pooled prevalence of symptoms in post-COVID participants in 17 studies ranged from 15% (diarrhoea) to 47% (fatigue). Age was associated with higher prevalence of all symptoms except cough. Higher study quality was associated with lower prevalence of all symptoms, except loss of smell and cognitive symptoms. INTERPRETATION: The frequency of the majority of reported persistent symptoms was similar in SARS-CoV-2 positive cases and controls. This systematic review and meta-analysis highlights the critical importance of a control group in studies on CYP post SARS-CoV-2 infection.

Change of refractive state and eye size in children of birth weight less than 1701 g.

AIMS: To determine the refractive status and ocular dimensions of a cohort of children at age 10-12 years with birth weight below 1701 g, and also the relation between the neonatal ophthalmic findings and subsequent refractive state. METHODS: 293 low birthweight children who had been examined in the neonatal period were assessed at 10-12 years of age. The examination consisted of autorefraction, keratometry, and A-scan. Results of right eyes were compared with published normative data. RESULTS: 293 of the birth cohort of 572 children consented to participate. The average mean spherical equivalent (MSE) in the low birthweight cohort was +0.691 dioptre, significantly higher than the control data (+0.30D, p = 0.02). The average change in MSE over the 10-12 year period was -1.00 dioptre (n = 256), but only 62.1% of cases showed a shift in refractive error of the appropriate magnitude and direction. The presence of any retinopathy of prematurity (ROP) increases the risk of developing anisometropia sixfold. CONCLUSIONS: Low birth weight and ROP both significantly impact the refractive state in the long term. At age 10-12 years children born preterm have an increased prevalence of all refractive errors. In low birthweight children refractive state is relatively stable over the first decade of life with a shift towards myopia of 1 dioptre.

The occurrence of terminal ileal histological abnormalities in patients with coeliac disease.

INTRODUCTION: Coeliac disease causes histological changes throughout the small bowel, but is often a proximal lesion. We wanted to assess whether terminal ileal histological abnormalities occurred more commonly in patients with coeliac disease and if specific assessment of intraepithelial lymphocytes increases the recognition of undiagnosed coeliac disease. METHODS: Terminal ileal biopsies were prospectively examined over a 3-year period (April 2001-May 2004). Patients were included if they were found to have a synchronous duodenal biopsy that gave a new diagnosis of coeliac disease (n=20). Terminal ileal biopsies taken at colonoscopy during the same period were also examined from four groups of patients: coeliac disease established on a gluten-free diet but with persisting symptoms (n=25), inflammatory bowel disease (n=47), chronic diarrhoea (n=44) and polyp surveillance (n=47). All biopsies were graded according to the Marsh criteria and an intraepithelial lymphocytes count per 100 enterocytes was obtained. RESULTS: There was only one patient from all five groups who had villous atrophy of the terminal ileal. This patient had a new diagnosis of coeliac disease. The mean intraepithelial lymphocytes count in the coeliac disease group was 23.7 intraepithelial lymphocytes/100 enterocytes. This was significantly higher than the control groups: coeliac disease on a gluten-free diet=17.5 (p<0.012), inflammatory bowel disease=12.3 (p<0.0001), diarrhoea=12.6 (p<0.0001) and polyp=13.7 (p<0.0002). Validating terminal ileal villous intraepithelial lymphocytes counts as a test for coeliac disease using an intraepithelial lymphocytes/100 enterocytes of >25 gives a sensitivity of 45% and a specificity of 97.8%. CONCLUSION: Routinely quantifying terminal ileal intraepithelial lymphocytes may be of limited clinical value. However, subjective recognition of raised intraepithelial lymphocytes on a terminal ileal biopsy should alert the clinician to the possibility of coeliac disease.

Nm23 protein expression in ductal in situ and invasive human breast carcinoma.

BACKGROUND: Mortality associated with human breast carcinoma is almost entirely due to subsequent metastatic disease, but the molecular basis of this metastasis is not understood. Elucidation of the genetic control of metastatic propensity of a tumor is important in determining prognosis and choice of therapy. Expression of nm23, a putative metastasis suppressor gene, has been detected in human breast cancers, but studies have not consistently shown high levels of the Nm23 messenger RNA or protein to be associated with better histological differentiation. This inconsistency suggests that Nm23 protein may act independently as a metastasis suppressor. PURPOSE: The purpose of this retrospective study was to investigate the relationship of Nm23 protein expression with 1) histology in ductal breast carcinoma in situ and 2) the variables considered to be the major prognostic indicators in invasive breast carcinoma. METHODS: We obtained formalin-fixed biopsy specimens of breast tissue excised from 128 patients with breast lesions detected by mammography. Of these patients, 35 had been diagnosed with benign breast disease, 26 with ductal carcinoma in situ (DCIS), and 67 with invasive carcinoma. Tissue sections were embedded in paraffin blocks, and immunohistochemical staining was used to determine Nm23 expression. Specimens were rated positive if all lesional epithelium was stained and negative if any lesional epithelium was unstained. Statistical analysis was performed by multiple regression analysis because of nonorthogonality of the data. RESULTS: All 35 examples of benign breast disease showed uniform epithelial cell staining. The seven cases of comedo DCIS were negative for Nm23 protein; all 18 noncomedo types were positive. Nm23 negativity was significantly associated with worsening invasive ductal carcinoma grade and advancing lymph node stage but not with tumor diameter or vascular invasion. Despite the putative antimetastatic role of the nm23 gene, no statistically significant association was found between Nm23 protein expression and vascular invasion. CONCLUSIONS: The precise role of the nm23 gene remains to be established, but our simplified immunohistochemical rating system shows an association between Nm23 protein expression and the two most significant prognostic factors relating to histologic grade and stage. Nm23 negativity distinguished comedo ductal carcinoma in situ from the other histological types, a finding consistent with the fact that comedo histology is known to have a higher likelihood of becoming invasive and of having higher cell proliferation rates and higher expression of growth factor (c-erb B2) receptor.

HER2 amplification status in breast cancer: a comparison between immunohistochemical staining and fluorescence in situ hybridisation using manual and automated quantitative image analysis scoring techniques.

AIMS: To compare the results of breast cancer sections with HercepTesttrade mark immunohistochemistry (IHC) scores ranging from 0 to 3+ with fluorescence in situ hybridisation (FISH) for HER2 amplification. The HER2 digital scoring application of the Micrometastasis Detection System (MDS) was used, together with manual scoring of FISH and HercepTest, to determine whether this system provides an accurate alternative. METHODS: Paraffin wax embedded sections were stained using HercepTest and analysed by eye and automated quantitative image analysis. FISH was performed using the PathVysion fluorescent probe and scored by eye and automated quantitative image analysis using MDS. RESULTS: Of 114 cases, 26% were amplified by FISH, whereas only 18% scored 3+; 32% of IHC 2+ cases were amplified by FISH, and one showed borderline amplification. Six percent of IHC negative cases (0 or 1+) were amplified by FISH, and one showed borderline amplification. Of IHC 3+ cases, 10% were non-amplified by FISH. Classification discrepancies were seen in 18% of HercepTest cases scored by eye and using the MDS system. MDS was consistent with visual FISH scoring and correctly differentiated most ambiguous visual IHC scores. CONCLUSIONS: FISH provides a more accurate and consistent scoring system for determining HER2 amplification than HercepTest. The MDS system provides a reliable, consistent alternative to visual IHC and FISH scoring. IHC is still a valuable technique to aid in identification of isolated or heterogeneous tumour populations for subsequent FISH analysis, and a combined FISH and HercepTest approach to all breast cancer cases may be the most efficient strategy.

Effect of soy protein-rich diet on renal function in young adults with insulin-dependent diabetes mellitus.

BACKGROUND: Diabetic nephropathy is the most frequent cause of end-stage renal disease in the Western world. Dietary intake, including protein amount and type, seems to affect the progression of renal disease. This pilot study tested the hypothesis that substituting soy protein for animal protein in the diets of diabetics would help correct glomerular hyperfiltration. METHODS: Twelve young adults (aged 29.9 +/- 2.4 years) with type 1 diabetes mellitus (duration of diabetes 15.1 +/- 2.3 years) and hyperfiltration (glomerular filtration rate, GFR > 120 ml/min/1.73 m2) completed a crossover, dietary intervention trial. After a four-week assessment of baseline characteristics and dietary habits, subjects were assigned to either a control or soy diet for eight weeks after which each subject was crossed over to the alternative diet for another eight-week period. RESULTS: Mean GFR was significantly reduced (p < 0.02) after eight weeks on the soy diet (143 +/- 7.4 ml/min/1.73 m2) compared with baseline (159 +/- 7.7 ml/min/ 1.73 m2) and control diets (161 +/- 10.0 ml/min/1.73 m2). Urinary excretion of the soy isoflavones was significantly higher (p < 0.01) at the end of the soy diet (genistein 1,014.6 +/- 274.1 nmol/h, daidzein 2,645.1 +/- 989.6 nmol/h) compared with baseline (genistein 53.7 +/- 31.1 nmol/h, daidzein 151.1 +/- 74.1 nmol/h) and control diets (genistein 41.1 +/- 13.3 nmol/h, daidzein 127.5 +/- 54.0 nmol/h). The soy diet significantly reduced total and LDL cholesterol by 7% and 9%, respectively. CONCLUSIONS: Implementation of a soy-based diet appears to reduce the GFR and total and LDL cholesterol of young adults with type 1 diabetes and glomerular hyperfiltration, thus affecting positively their clinical profile.

Differences in hair follicle dermal papilla volume are due to extracellular matrix volume and cell number: implications for the control of hair follicle size and androgen responses.

The size of a hair follicle is thought to be determined by the volume of its dermal papilla. The volume of the dermal papilla depends on the number of cells it contains and on the volume of the extracellular matrix. To establish which of these two variables is related to differences in hair follicle size we performed a stereologic study on 235 hair follicles from different sites, including male facial skin (beard), female facial skin, and scalp. In facial follicles there was a strong correlation between the area of the hair cortex and the volume of the dermal papilla. The area of the hair cortex also correlated with the number of cells in the dermal papilla and with the volume of dermal papilla per cell. In scalp hair follicles, where there was a smaller range of sizes, the correlations between these variables were weaker. In large male facial follicles the mean total dermal papilla volume was almost 40-fold higher than in vellus follicles from female facial skin. This difference was associated with a mean 17-fold greater number of cells in the dermal papilla and a 2.4-fold greater volume associated with each cell. Intermediate results were obtained in scalp follicles. In many regions of the skin hair follicles enlarge in response to androgens during adult life hair. Our results imply that the increase in the volume of the dermal papilla in these follicles is due to an increase in the number of cells, either through proliferation or through the migration of cells from the follicular dermal sheath, and to an increase in the amount of extracellular matrix per cell. As androgens are thought to act primarily on the dermal papilla, these changes may have a direct bearing on the mechanism of androgen-mediated alterations in hair follicle size.

Maternal nutrition alters the expression of insulin-like growth factors in fetal sheep liver and skeletal muscle.

We investigated the influence of maternal dietary restriction between days 28 and 80 of gestation followed by re-feeding to the intake of well-fed ewes up to 140 days of gestation (term is 147 days) in sheep, on expression of mRNA for insulin-like growth factor (IGF)-I, IGF-II and growth hormone receptor (GHR) in fetal liver and skeletal muscle. Singleton bearing ewes either consumed 3.2-3.8 MJ/day of metabolisable energy (ME) (i.e. nutrient restricted - approximately 60% of ME requirements, taking into account requirements for both ewe maintenance and growth of the conceptus) or 8.7-9.9 MJ/day (i.e. well fed - approximately 150% of ME requirements) between days 28 and 80 of gestation. All ewes were then well fed (150% of ME requirements) up to day 140 of gestation and consumed 8-10.9 MJ/day. At days 80 and 140 of gestation, five ewes were sampled from each group and fetal tissues taken. There was no difference in fetal body weight or liver weights between groups at either sampling date, or skeletal muscle (quadriceps) weight at 140 days. IGF-I mRNA abundance was lower in livers of nutrient-restricted fetuses at day 80 of gestation (nutrient restricted 2.35; well fed 3.70 arbitrary units), but was higher than well-fed fetuses at day 140 of gestation, after 60 days of re-feeding (restricted/re-fed 4.27; well fed 2.83;s.e.d. 0.98 arbitrary units, P=0.061 for dietxage interaction). IGF-II mRNA abundance was consistently higher in livers of nutrient-restricted fetuses (80 days: nutrient restricted 7.78; well fed 5.91; 140 days: restricted/re-fed 7.23; well fed 6.01;s.e.d. 1.09 arbitrary units, P=0.061 for diet). Nutrient restriction had no effect on hepatic GHR mRNA abundance, but re-feeding of previously nutrient-restricted fetuses increased GHR mRNA compared with continuously well-fed fetuses (80 days: nutrient restricted 70.6; well fed 75.1; 140 days: restricted/re-fed 115.7; well fed 89.4;s.e.d. 10.13 arbitrary units, P=0.047 for dietxage interaction). In fetal skeletal muscle, IGF-I mRNA abundance was not influenced by maternal nutrition and decreased with gestation age (P<0.01). IGF-II mRNA abundance was higher in skeletal muscle of nutrient-restricted fetuses compared with well-fed fetuses at day 80 of gestation (nutrient restricted 16.72; well fed 10.53 arbitrary units), but was lower than well-fed fetuses after 60 days of re-feeding (restricted/re-fed 7.77; well fed 13.72;s.e.d. 1.98 arbitrary units, P<0.001 for dietxage interaction). There was no effect of maternal nutrition or gestation age on fetal skeletal muscle GHR expression. In conclusion, maternal nutrient restriction in early to mid gestation with re-feeding thereafter results in alterations in hepatic and skeletal muscle expression of IGF-I, IGF-II and/or GHR in the fetus which may subsequently relate to altered organ and tissue function.

Endoscopic ablation of Barrett's oesophagus: a randomized-controlled trial of photodynamic therapy vs. argon plasma coagulation.

BACKGROUND: Barrett's oesophagus is the major risk factor for oesophageal adenocarcinoma. 5-Aminlevulinic acid-induced photodynamic therapy and argon plasma coagulation have been shown to be effective for ablating Barrett's oesophagus, but a comparative trial of these two modalities has not been reported. AIMS: To compare photodynamic therapy and argon plasma coagulation for the ablation of Barrett's oesophagus. METHODS: A total of 68 patients (54 male, 14 female; median age 61) with Barrett's oesophagus were randomized to photodynamic therapy (n = 34) or argon plasma coagulation (n = 34). Photodynamic therapy was performed using 5-aminlevulinic acid (30 mg/kg) and red light. Argon plasma coagulation was administered at a power setting of 65 W. Multiple treatment sessions were performed, with follow-up to 24 months. RESULTS: All patients showed a macroscopic reduction in the area of Barrett's oesophagus. This was greatest in the argon plasma coagulation group with 33 of 34 (97%) ablated, compared with 17 of 34 (50%) in the photodynamic therapy group; in the remainder, there was a reduction in the length of Barrett's oesophagus (median 50%, range: 5-90). Buried glands were found in 24% of photodynamic therapy patients, and in 21% of argon plasma coagulation patients. The median follow-up is 12 months (range: 6-24). CONCLUSIONS: Photodynamic therapy and argon plasma coagulation are both effective for ablating Barrett's oesophagus. Argon plasma coagulation appears more effective than photodynamic therapy, but the impact of both on carcinoma development requires larger studies with long-term follow-up.

Visceral brown fat necrosis in postperinatal mortality.

Fat necrosis was present in 22 of 400 cases of consecutive postperinatal mortalities investigated to assess the presence and pattern of deep fat necrosis. In just over 50% of the cases of fat necrosis the cause of death was categorised as sudden infant death syndrome, which also showed more severe degrees of necrosis. The mechanism of necrosis may be vascular hypoperfusion, possibly related to shock, and brown adipose tissue, on account of its high metabolic activity and rich capillary plexus, may be particularly vulnerable to infarction. The occurrence of fat necrosis in association with other causes of death did not provide any definite clue as to the nature of the alleged shock.

Are clinicians failing to supply adequate information when requesting a histopathological investigation?

AIMS: There is a perception among histopathologists that specimens are often received without adequate clinical details. This is the first study to determine the adequacy of information provided when histopathological investigations are requested. METHODS: Two thousand sequential requests for histological examination were assessed for adequacy and completeness. RESULTS: There was no significant difference in the demographic details supplied by physicians and surgeons. Clinical details were inadequate in 6.1% of cases: those from physicians were significantly more often adequate (98.7% v 90.6%) and more often included a diagnosis (74.4% v 38.8%) than those from surgeons. Physicians were more likely to supply their name and contact number but requests frequently lacked details of the sender. CONCLUSIONS: Specimens are infrequently received with inadequate demographic details, but clinical details and details of the sender are more often lacking. Education of clinical colleagues is required if pathologists are to manage the demand for the service.

Ablation treatment for Barrett oesophagus: what depth of tissue destruction is needed?

AIM: To establish the depth of Barrett's columnar epithelium and normal squamous oesophageal epithelium, in order to determine the depth of destruction required in ablation treatment for Barrett oesophagus. METHODS: Histological specimens from 100 cases of Barrett oesophagus and 100 samples of normal squamous oesophageal epithelium were studied. Using a system of multiple measurements until the change in cumulative mean values varied by less than 5%, the overall mean and normal range of depth was calculated for each type of epithelium. RESULTS: Barrett columnar epithelium is minimally thicker (mean (SEM) 0.50 (0.004) mm; range 0.39 to 0.59 mm) than normal squamous epithelium (0.49 (0.003) mm; 0.42 to 0.58 mm), although this difference is probably too small to be of clinical relevance. CONCLUSIONS: Although there are numerous clinical reports of various methods of ablation treatment for Barrett oesophagus, little attention has been paid to the depth of tissue destruction required. This is the first study to look specifically at this issue, and it provides information on the necessary depth of epithelial ablation.

Pseudomembranous trigonitis of the bladder: hormonal aetiology.

Fourteen formalin fixed and paraffin wax embedded biopsy specimens from 10 women (age range 34-68) presenting with pseudomembranous trigonitis were studied using a combination of anti-oestrogen receptor monoclonal antibodies in an avidin-biotin immunoperoxidase technique. All epithelial areas showing vaginal metaplasia exhibited staining confined to the nucleus in the basal and parabasal layers of the squamous epithelium while no staining was encountered in adjacent trigonal transitional epithelium included in nine of the biopsy specimens. The selective expression of nuclear oestrogen receptor in trigonal epithelium affected by vaginal metaplasia in a distribution similar to that reported in vaginal epithelium by other workers lends further support to oestrogen mediated aetiology in this condition and is consistent with an embryological derivation of the trigone, distinct from that of the rest of the bladder.

C-myc oncogene product P62c-myc in ovarian mucinous neoplasms: immunohistochemical study correlated with malignancy.

The monoclonal antibody Myc 1-6E10 was used to determine the cellular distribution of the c-myc oncogene product p62c-myc in 60 mucinous ovarian tumours. Three patterns of immunostaining were apparent: (i) nuclear staining alone; (ii) staining of the nucleus and basal cytoplasm; and (iii) staining of the entire cell. Of the 21 cases of mucinous cystadenoma, 11 showed nuclear staining alone, and a further case showed additional weak staining of the basal cytoplasm. Nuclear staining alone was not present in any of the 17 borderline mucinous tumours examined. Strong staining of the nucleus and basal cytoplasm was seen in 16 of these borderline cases, six of which also showed focal staining of the apical cytoplasm. All 22 cases of mucinous cystadenocarcinoma showed staining of the cell nucleus and entire cell cytoplasm. Focal staining of the apical cytoplasm in six of 17 borderline mucinous tumours produced a pattern of c-myc immunostaining similar to that of cystadenocarcinoma. Retrospective analysis of the clinical data showed that no significant differences between patients with borderline tumours of these two categories could be defined. Although immunostaining with Myc 1-6E10 can be used in the categorisation of mucinous ovarian tumours, it is concluded that standard histological criteria are more accurate indicators of tumour behaviour than is an assessment of c-myc expression.

Feasibility of new prognostic classification for rectal cancer.

Sixty slides from 60 blocks taken from 30 colonic carcinomas were circulated twice to six histopathologists of varying experience. Five of the six pathologists showed a good to excellent intraobserver agreement for assessment of the character of the invasive margin (0.44 less than kappa less than 0.82), which was not significantly affected by sampling (0.40 less than kappa less than 0.56, comparing both slides from each tumour) or observer (five of six pathologists agreeing on 46 of 60 slides). Pathologists were unreliable in assessing peritumoural lymphocytic infiltrates, with only two pathologists achieving moderate levels of intraobserver agreement (-0.03 less than kappa less than 0.52). The interobserver agreement for peritumoural lymphocytic infiltrates was also low (kappa less than 0.29) between the three most experienced pathologists. The assessment of peritumoural lymphocytic infiltrates was significantly affected by sampling, the two pathologists with the lowest intraobserver variation achieving kappa values of 0.21 and 0.10 between the 30 paired slides from each tumour. The character of the invasive margin was reliably assessed, was not dependent on sample, and added useful prognostic information, but peritumoural lymphocytic infiltration is not a reproducible observation and may therefore not add useful prognostic information in routine use.

Offline telepathology diagnosis of colorectal polyps: a study of interobserver agreement and comparison with glass slide diagnoses.

BACKGROUND/AIMS: Technological advances have produced telepathology systems with high quality colour images and reasonable transmission times. Most applications of telepathology have centred on the remote diagnosis of frozen sections or remote real time expert opinions. This study investigates the reproducibility and accuracy of offline telepathology as a primary diagnostic medium for routine histopathology specimens. METHODS: One hundred colorectal polyps (50 hyperplastic, 50 adenomatous) were presented in a randomised order to five histopathologists as offline images on a telepathology workstation. Six images of each case were used: the slide label, a low power scan of all material on the slide, and four higher magnification views. The times taken to prepare the images, and to make the diagnoses, were recorded. Interobserver agreement was measured with kappa statistics and compared with the glass slide diagnoses. RESULTS: The kappa statistics for the interobserver agreement on the telepathology images lay in the range of 0.90-1.00, which is interpreted as excellent agreement, and were significantly higher than those for the glass slide diagnoses (range, 0.84-0.98; p = 0.001). The median time taken to capture the images for a case was 210 seconds. The median time taken to make a diagnosis from the telepathology images was five seconds, which was significantly shorter than for the glass slide diagnoses (median, 13 seconds; p < 0.0005). CONCLUSIONS: Offline telepathology has the potential to be a primary diagnostic medium for routine histopathology with a high degree of reproducibility and short diagnosis times. Further studies are required to validate offline telepathology for different types of specimens and different operators of the image capture system.

Virtual biopsies in Barrett's esophagus using an impedance probe.

Preliminary results of electrical impedance measurements in squamous and columnar epithelia in rat and human tissues are presented. The aim of this work is to show the possibility of differentiating these two types of epithelia in terms of their electrical characteristics. For the measurements, we employed a 1.95-m-long, 3.2-mm-diameter, four-electrode probe designed to be used transendoscopically in the diagnosis of Barrett's esophagus (BE). BE is a condition in which the normal squamous epithelium of the esophagus is replaced by columnar epithelium of the intestinal type. This metaplasia is considered as a premalignant condition that puts patients at a 30-125-fold risk of developing adenocarcinoma of the esophagus. The diagnosis and surveillance of BE involve taking multiple biopsies, an expensive and time-consuming procedure. This study constitutes the first stage in the replacement of tissue biopsy by "virtual biopsies".

Gastric carcinoma in siblings with Friedreich's ataxia.

Friedreich's ataxia is a hereditary neurological condition characterized by severe ataxia. We report the cases of two siblings with this condition, both of whom developed signet ring cell adenocarcinoma of the stomach at a young age. This association has not been previously described and it suggests the presence of an unidentified aberrant gene.

Visual function in low birthweight children.

AIM: To determine the visual functions, at age 10-12 years, of a geographically based cohort of children of birth weight less than 1701 g. The results were compared to a group of children born at full term. METHODS: 572 low birthweight (LBW) "low birthweight cohort" children who had been examined in the neonatal period were invited for review at 10-12 years of age. 169 11 year old schoolchildren born at full term were also recruited, "school cohort." Visual acuity (at distance and near), contrast sensitivity, colour vision, and visual fields were measured. RESULTS: 293 of the original 572 participants consented to a further examination. Compared to the school cohort of children born at term the low birthweight cohort showed significantly lower near and distance acuities and contrast sensitivity (p<0.001 for all uniocular and binocular measures). Retinopathy of prematurity (ROP) was a very poor predictor of outcome and multivariate analysis did not identify any key neonatal factors as predictors of long term visual outcome. CONCLUSIONS: Low birthweight children have a small but statistically significant deficit in both visual acuity and contrast sensitivity. Low birth weight and ROP both impact on long term visual functions.