Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis.

BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5-10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.

Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding: a systematic review of clinical effectiveness and cost-effectiveness analysis.

OBJECTIVE: The aim of this project was to determine the clinical effectiveness and cost-effectiveness of hysterectomy, first- and second-generation endometrial ablation (EA), and Mirena® (Bayer Healthcare Pharmaceuticals, Pittsburgh, PA, USA) for the treatment of heavy menstrual bleeding. DESIGN: Individual patient data (IPD) meta-analysis of existing randomised controlled trials to determine the short- to medium-term effects of hysterectomy, EA and Mirena. A population-based retrospective cohort study based on record linkage to investigate the long-term effects of ablative techniques and hysterectomy in terms of failure rates and complications. Cost-effectiveness analysis of hysterectomy versus first- and second-generation ablative techniques and Mirena. SETTING: Data from women treated for heavy menstrual bleeding were obtained from national and international trials. Scottish national data were obtained from the Scottish Information Services Division. PARTICIPANTS: Women who were undergoing treatment for heavy menstrual bleeding were included. INTERVENTIONS: Hysterectomy, first- and second-generation EA, and Mirena. MAIN OUTCOME MEASURES: Satisfaction, recurrence of symptoms, further surgery and costs. RESULTS: Data from randomised trials indicated that at 12 months more women were dissatisfied with first-generation EA than hysterectomy [odds ratio (OR): 2.46, 95% confidence interval (CI) 1.54 to 3.93; p = 0.0002), but hospital stay [WMD (weighted mean difference) 3.0 days, 95% CI 2.9 to 3.1 days; p < 0.00001] and time to resumption of normal activities (WMD 5.2 days, 95% CI 4.7 to 5.7 days; p < 0.00001) were longer for hysterectomy. Unsatisfactory outcomes associated with first- and second-generation techniques were comparable [12.2% (123/1006) vs 10.6% (110/1034); OR 1.20, 95% CI 0.88 to 1.62; p = 0.2). Rates of dissatisfaction with Mirena and second-generation EA were similar [18.1% (17/94) vs 22.5% (23/102); OR 0.76, 95% CI 0.38 to 1.53; p = 0.4]. Indirect estimates suggested that hysterectomy was also preferable to second-generation EA (OR 2.32, 95% CI 1.27 to 4.24; p = 0.006) in terms of patient dissatisfaction. The evidence to suggest that hysterectomy is preferable to Mirena was weaker (OR 2.22, 95% CI 0.94 to 5.29; p = 0.07). In women treated by EA or hysterectomy and followed up for a median [interquartile range (IQR)] duration of 6.2 (2.7-10.8) and 11.6 (7.9-14.8) years, respectively, 962/11,299 (8.5%) women originally treated by EA underwent further gynaecological surgery. While the risk of adnexal surgery was similar in both groups [adjusted hazards ratio 0.80 (95% CI 0.56 to 1.15)], women who had undergone ablation were less likely to need pelvic floor repair [adjusted hazards ratio 0.62 (95% CI 0.50 to 0.77)] and tension-free vaginal tape surgery for stress urinary incontinence [adjusted hazards ratio 0.55 (95% CI 0.41 to 0.74)]. Abdominal hysterectomy led to a lower chance of pelvic floor repair surgery [hazards ratio 0.54 (95% CI 0.45 to 0.64)] than vaginal hysterectomy. The incidence of endometrial cancer following EA was 0.02%. Hysterectomy was the most cost-effective treatment. It dominated first-generation EA and, although more expensive, produced more quality-adjusted life-years (QALYs) than second-generation EA and Mirena. The incremental cost-effectiveness ratios for hysterectomy compared with Mirena and hysterectomy compared with second-generation ablation were £1440 per additional QALY and £970 per additional QALY, respectively. CONCLUSIONS: Despite longer hospital stay and time to resumption of normal activities, more women were satisfied after hysterectomy than after EA. The few data available suggest that Mirena is potentially cheaper and more effective than first-generation ablation techniques, with rates of satisfaction that are similar to second-generation techniques. Owing to a paucity of trials, there is limited evidence to suggest that hysterectomy is preferable to Mirena. The risk of pelvic floor surgery is higher in women treated by hysterectomy than by ablation. Although the most cost-effective strategy, hysterectomy may not be considered an initial option owing to its invasive nature and higher risk of complications. Future research should focus on evaluation of the clinical effectivesness and cost-effectiveness of the best second-generation EA technique under local anaesthetic versus Mirena and types of hysterectomy such as laparoscopic supracervical hysterectomy versus conventional hysterectomy and second-generation EA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Hysterectomy, endometrial destruction, and levonorgestrel releasing intrauterine system (Mirena) for heavy menstrual bleeding: systematic review and meta-analysis of data from individual patients.

OBJECTIVE: To evaluate the relative effectiveness of hysterectomy, endometrial destruction (both "first generation" hysteroscopic and "second generation" non-hysteroscopic techniques), and the levonorgestrel releasing intrauterine system (Mirena) in the treatment of heavy menstrual bleeding. DESIGN: Meta-analysis of data from individual patients, with direct and indirect comparisons made on the primary outcome measure of patients' dissatisfaction. DATA SOURCES: Data were sought from the 30 randomised controlled trials identified after a comprehensive search of the Cochrane Library, Medline, Embase, and CINAHL databases, reference lists, and contact with experts. Raw data were available from 2814 women randomised into 17 trials (seven trials including 1359 women for first v second generation endometrial destruction; six trials including 1042 women for hysterectomy v first generation endometrial destruction; one trial including 236 women for hysterectomy v Mirena; three trials including 177 women for second generation endometrial destruction v Mirena). Eligibility criteria for selecting studies Randomised controlled trials comparing hysterectomy, first and second generation endometrial destruction, and Mirena for women with heavy menstrual bleeding unresponsive to other medical treatment. RESULTS: At around 12 months, more women were dissatisfied with outcome with first generation hysteroscopic techniques than with hysterectomy (13% v 5%; odds ratio 2.46, 95% confidence interval 1.54 to 3.9, P<0.001), but hospital stay (weighted mean difference 3.0 days, 2.9 to 3.1 days, P<0.001) and time to resumption of normal activities (5.2 days, 4.7 to 5.7 days, P<0.001) were longer for hysterectomy. Unsatisfactory outcomes were comparable with first and second generation techniques (odds ratio 1.2, 0.9 to 1.6, P=0.2), although second generation techniques were quicker (weighted mean difference 14.5 minutes, 13.7 to 15.3 minutes, P<0.001) and women recovered sooner (0.48 days, 0.20 to 0.75 days, P<0.001), with fewer procedural complications. Indirect comparison suggested more unsatisfactory outcomes with second generation techniques than with hysterectomy (11% v 5%; odds ratio 2.3, 1.3 to 4.2, P=0.006). Similar estimates were seen when Mirena was indirectly compared with hysterectomy (17% v 5%; odds ratio 2.2, 0.9 to 5.3, P=0.07), although this comparison lacked power because of the limited amount of data available for analysis. CONCLUSIONS: More women are dissatisfied after endometrial destruction than after hysterectomy. Dissatisfaction rates are low after all treatments, and hysterectomy is associated with increased length of stay in hospital and a longer recovery period. Definitive evidence on effectiveness of Mirena compared with more invasive procedures is lacking.

PTCH mutations in basal cell carcinomas from azathioprine-treated organ transplant recipients.

The immunosuppressant azathioprine is used to prevent graft rejection after organ transplantation. To investigate whether azathioprine-associated mutagenesis contributes to the high incidence of skin tumours in organ transplant recipients (OTRs), we analysed PTCH gene mutations in 60 basal cell carcinomas (BCC); 39 from OTRs receiving azathioprine and 21 from individuals never exposed to azathioprine. PTCH was mutated in 55% of all tumours, independent of azathioprine treatment. In both the azathioprine and non-azathioprine groups, transitions at dipyrimidine sequences, considered to indicate mutation by ultraviolet-B radiation, occurred frequently in tumours from chronically sun-exposed skin. In BCC from non-sun-exposed skin of azathioprine-treated patients, there was an over-representation of unusual G:C to A:T transitions at non-dipyrimidine sites. These were exclusive to the azathioprine-exposed group and all in the same TGTC sequence context at different positions within PTCH. Meta-analysis of 247 BCCs from published studies indicated that these mutations are rare in sporadic BCC and had never previously been reported in this specific sequence context. This study of post-transplant BCC provides the first indication that azathioprine exposure may be associated with PTCH mutations, particularly in tumours from non-sun-exposed skin.

The usefulness of the platelet function analyser (PFA-100) in screening for underlying bleeding disorders in women with menorrhagia.

The prevalence of underlying bleeding disorders is common in women with menorrhagia. This was a prospective study to screen for the underlying bleeding disorders in women presenting with menorrhagia by using the PFA-100 and comparing the accuracy of the results with the complete haematological assays. A total of 62 women referred to gynaecology outpatients with a history of heavy, regular periods had blood collected for analysis by the PFA-100 and also a full coagulation profile including von Willebrand factor. PFA-100 analysis suggested platelet defects in 10 (16%) women. This included five (8%) identified with von Willebrand disease, two (3.2%) with storage pool disorders and three (4.8%) without any recognisable platelet or bleeding disorders after a full coagulation profile, including von Willebrand factor, was carried out. PFA-100 results had a sensitivity of 100% and specificity of 94.8% in our study. We conclude that PFA-100 is a quick and reliable method of screening for impaired haemostasis in patients with menorrhagia.

Azathioprine treatment photosensitizes human skin to ultraviolet A radiation.

BACKGROUND: Azathioprine is used to treat a variety of conditions and to prevent graft rejection in organ transplant recipients (OTRs). OBJECTIVES: To investigate clinically our previous finding that azathioprine metabolites interact with ultraviolet (UV) A radiation to form promutagenic oxidative DNA damage and to determine whether this may be causal or contributory to the development of excess skin cancers post-transplantation. METHODS: The clinical corollary of these data were investigated. Five patients were recruited and the minimal erythema dose (MED) for UVB, UVA and solar-simulated radiation (SSR) was determined for each person before, and at least 12 weeks after, starting azathioprine therapy. RESULTS: In all five patients azathioprine treatment was associated with an increased UVA and SSR sensitivity of the skin and a significant reduction in MEDs for UVA and SSR. We found no change in UVB-induced erythema or MED. In addition, we found that DNA from the skin of patients on azathioprine contains 6-thioguanine (6-TG). CONCLUSIONS: Our findings confirm the presence of DNA 6-TG in the skin of those taking therapeutic doses of azathioprine and provide support for the hypothesis that DNA damage occurs when DNA 6-TG interacts with UVA, resulting in abnormal cutaneous photosensitivity.

Are endometrial polyps from pre-menopausal women similar to post-menopausal women? An immunohistochemical comparison of endometrial polyps from pre- and post-menopausal women.

OBJECTIVE: Do endometrial polyps from pre- and post-menopausal women have similar immunohistochemical expression of oestrogen and progesterone receptors (ER, PR) and markers of cellular proliferation/apoptosis (Ki67 and Bcl-2). DESIGN: Prospective cohort study. Non-parametric statistical analysis was used. SETTING: Polyps recruited from women attending an out-patient hysteroscopy clinic in a UK district general hospital. PATIENTS: Fourteen pre-menopausal and 16 post-menopausal women who presented with abnormal bleeding with endometrial polyps. INTERVENTIONS: Immunohistochemical staining was performed on endometrial polyps. MAIN OUTCOME MEASURES: Significant differences or correlations between hormone receptor expression (oestrogen and progesterone) and cell growth indices (Ki67 and Bcl-2). RESULTS: Endometrial polyps from pre- and post-menopausal women had significant differences in their expression of hormone receptors and Ki67. However, polyps from both groups of women had similarly increased levels of Bcl-2, an inhibitor of apoptosis. CONCLUSIONS: Pre- and post-menopausal polyps exhibit differing hormone receptor and proliferation markers, presumably a result of their hormonal milieu. However, both groups appear to have lost the usual control mechanisms for apoptotic regulation, this appears to be responsible for their growth.

Does tamoxifen therapy affect the hormone receptor expression and cell proliferation indices of endometrial polyps? An immunohistochemical comparison of endometrial polyps from postmenopausal women exposed and not exposed to tamoxifen.

OBJECTIVE: This study set out to test the null hypothesis that tamoxifen therapy would not affect the hormone receptor expression (oestrogen and progesterone receptors-ER and PR) or markers of cell proliferation/apoptosis (Ki67 and Bcl-2) of endometrial polyps from postmenopausal women exposed and not exposed to tamoxifen. METHODS: Endometrial polyps were prospectively obtained from women presenting with abnormal bleeding attending an out-patient hysteroscopy clinic who subsequently underwent endometrial polypectomy (16 from postmenopausal women not exposed to tamoxifen, 9 from women exposed to tamoxifen). Immunohistochemical staining for ER, PR, Ki67 and Bcl-2 was performed on polyps from both groups of women. Non-parametric statistical analysis was used (Mann-Whitney and Spearmans rank correlation). RESULTS: Endometrial polyps from tamoxifen users had significantly lower oestrogen receptor but increased progesterone receptor and Bcl-2 expression. There were no significant differences for proliferation markers (Ki67) between postmenopausal endometrial polyps exposed and not exposed to tamoxifen. CONCLUSIONS: Tamoxifen has a significant affect on hormone receptor expression and markers of apoptosis in endometrial polyps. The results support the hypothesis that tamoxifen promotes polyp growth by inhibiting apoptosis. The mechanism for this does not appear to be oestrogen receptor mediated.

An immunohistochemical comparison of endometrial polyps from postmenopausal women exposed and not exposed to HRT.

OBJECTIVE: Our study set out to test the null hypothesis that oestrogen containing continuous combined hormone replacement therapy (HRT) would not affect the hormone receptor expression (oestrogen and progesterone receptors-ER, PR) or markers of cell proliferation/apoptosis (Ki67 and Bcl-2) in endometrial polyps from postmenopausal women exposed and not exposed to HRT. DESIGN: Immunohistochemical staining for ER, PR, Ki67 and Bcl-2 was performed on polyps obtained from two groups of postmenopausal women. SETTING: Polyps were obtained from postmenopausal women attending an outpatient hysteroscopy clinic in a district general hospital (Bradford Royal Infirmary, UK). POPULATION: Twenty-five postmenopausal women presenting with abnormal bleeding subsequently diagnosed with endometrial polyps (16 from women not exposed to HRT, 9 from women exposed to HRT). METHODS: Semiquantitative immunohistochemistry was performed. MAIN OUTCOME MEASURES: Significant differences or correlations in either hormone receptor expression or markers of cell proliferation/apoptosis between the two groups of polyps. RESULTS: There were no significant differences for hormone receptor expression (ER and PR) between endometrial polyps exposed and not exposed to HRT. Bcl-2 expression was higher than Ki67 in both groups, but polyps from HRT users had increased levels reflecting decreased apoptosis in these polyps. CONCLUSIONS: HRT has no demonstrable effect on polyp ER and PR expression. However, HRT does appear to inhibit apoptosis and cell proliferation in endometrial polyps, which may affect polyp growth.

Selecting distending medium for out-patient hysteroscopy. Does it really matter?

BACKGROUND: The aim of this prospective randomized study was to evaluate the role of carbon dioxide (CO2) and normal saline for diagnostic accuracy in out-patient hysteroscopy. METHODS: Women admitted to our Department in order to undergo total abdominal hysterectomy also underwent diagnostic hysteroscopy, 12-24 h prior to surgery. The selection of distending medium was made after randomization. Two groups of patients were formed, group A (CO2; n=39) and group B (normal saline; n=35). More than half of the women in the study population were post-menopausal. Post-hysteroscopy, all women were asked to rank any symptom that they felt during the procedure on a 4-point scale (0=none; 1=mild; 2=severe; 3=inability to perform hysteroscopy). The hysteroscopic diagnosis was compared with the macroscopic findings and the histological examination of the surgical specimen after hysterectomy. RESULTS: The percentage who completed hysteroscopy was 89.74% within group A and 97.14% within group B. Most patients of both groups felt some pain of mild intensity. The diagnostic accuracy of hysteroscopy was similar for both media when major pathology [large polyps (group A 91.7%; group B 92.7%), myomas (group A 81.25%; group B 92.7%) and/or hyperplasia (group A 87.5%; group B 90.2%)] of the endometrial cavity was detected. In contrast, in cases of minor pathology (small polyps, mucosal elevations, crypts, hypervascularization), hysteroscopy with saline presented with significantly higher diagnostic accuracy (85.4%) compared with hysteroscopy with CO2 (64.6%). CONCLUSIONS: In out-patient hysteroscopy, CO2 and normal saline were comparable with regard to patient discomfort and for the detection of major pathology of the endometrial cavity. Normal saline seems to be the most appropriate medium for the detection of minor pathology of the endometrial cavity.

Outcome of outpatient micro-hysteroscopy performed for abnormal bleeding while on hormone replacement therapy.

This retrospective observational study was carried out in a large district general hospital to review the outcome of outpatient micro-hysteroscopy performed on women with abnormal bleeding while on hormone replacement therapy. All women referred to the outpatient hysteroscopy unit with abnormal bleeding while on hormone replacement therapy between November 1994 and August 1998 had hysteroscopy performed using a 1.2 mm semi-rigid hysteroscope with a 2.5 mm sheath. Hysteroscopy was performed on 190 women. Ninety-two women (48.4%) had a normal uterine cavity, 38 (20%) had an atrophic endometrium, 52 (27.4%) were found to have endometrial polyps, seven (3.7%) had suspicious endometrium (histology showed two adenocarcinomas and three hyperplasias) and one patient (0.5%) had a submucous fibroid. Histological evaluation showed 145 (76.32%) specimens were benign, 37 (19.47%) specimens either contained no tissue or insufficient tissue for diagnosis, five (2.63%) showed hyperplasia and three (1.58%) were adenocarcinoma. Two hyperplasias and one focal adenocarcinoma were diagnosed in endometrial polyps. Nearly half of the women who had a hysteroscopy for abnormal bleeding while on hormone replacement therapy had a normal endometrial cavity. Almost one-third had endometrial pathology, of which the majority were endometrial polyps. The incidence of endometrial carcinoma was low. No abnormality was missed on hysteroscopy, but histology was normal in two patients with hysteroscopically suspicious endometrium.

Microwave endometrial ablation in the management of menorrhagia: current status.

Menorrhagia is a common clinical problem. Recently several different ablative techniques have been described to treat it in the expectation of reducing hysterectomy rates. This paper describes the current status of microwave endometrial ablation, its clinical efficacy, its safety profile and future development.

Microlaparoscopy.

Microlaparoscopy is defined as using instruments with an outer sheath of less than 2 mm; as such, it represents the leading edge of fiberoptic and instrument design technology. Although still in its infancy, it has been proposed as the new standard instrument for abdominal entry and for the performance of some diagnostic and therapeutic procedures. It is already the instrument of choice for performing conscious laparoscopic procedures. The small size of the instrument makes it versatile, but it is important that they are used appropriately. In this way, microlaparoscopy offers significant advantages over conventional laparoscopy for surgeon and patient alike.

Acute pulmonary edema after lung transplantation: the pulmonary reimplantation response.

BACKGROUND: Although the development of noncardiogenic pulmonary edema or pulmonary reimplantation response (PRR) after lung transplantation has been well described, the incidence has not been established and the relationship of PRR to clinical risk factors has not been analyzed. STUDY OBJECTIVES: (1) To describe the incidence of PRR in lung transplant recipients, (2) to identify the predictors of PRR, (3) to examine the correlation of suspected predictors with the severity of PRR, and (4) to evaluate the impact of PRR on morbidity and mortality of lung transplant recipients. DESIGN: Retrospective review of clinical records and radiographic studies. SETTING: Tertiary care referral center. PATIENTS: Ninety-nine consecutive patients with end-stage lung disease undergoing lung transplantation between February 1990 and October 1995. METHODS: Review of clinical records and postoperative chest radiographs of all lung transplant recipients to identify patients who experienced PRR. Chest radiographs of patients with PRR were graded for severity on a scale of 0 (none) to 5 (very severe). Demographic, pre- and perioperative factors were also evaluated along with short- and long-term survival of patients with PRR. RESULTS: Fifty-six of 99 lung transplant recipients (57%) experienced PRR. The median ischemia time of patients with and without PRR was 168 and 180 min, respectively (p = 0.62). The incidence of PRR was 51% in patients without preoperative pulmonary hypertension, 78% in mild to moderate pulmonary hypertension, and 58% in patients with severe pulmonary hypertension (p = 0.10). Incidence and severity of PRR was similar in patients receiving right, left, or double-lung transplantation. Similarly, age and sex of the recipients and underlying lung disease did not affect the incidence or severity of PRR. The incidence and severity of PRR was higher in patients undergoing cardiopulmonary bypass during lung transplantation. Patients with PRR had prolonged duration of mechanical ventilation and ICU stay. Overall, PRR did not affect the survival of the patients. However, survival of female lung transplant recipients was significantly better than male recipients (median survival, 60 vs 21 months; p = 0.02). CONCLUSIONS: Acute pulmonary edema or PRR occurs frequently (57%) after lung transplantation. In this series, PRR was not associated with a prolonged ischemia time, preoperative pulmonary hypertension, the type of lung transplant, underlying lung disease, or age or sex of recipients. However, use of cardiopulmonary bypass during surgery was associated with increased incidence and severity of PRR. Also, the development of PRR resulted in prolonged mechanical ventilation and a longer ICU stay, but did not affect survival. Female lung transplant recipients survived significantly longer than male recipients. The reason for this difference in survival is unclear.

Transudative malignant pleural effusions: prevalence and mechanisms.

BACKGROUND: Malignant pleural effusions are classically exudative, though occasionally they can be transudative. We attempted to determine the prevalence of transudative malignant pleural effusions and to describe their clinical and radiographic characteristics. METHODS: We studied the medical records of 215 patients with malignant pleural effusion, which contained complete data on pleural fluid analysis for 171 of them. RESULTS: Eight cases of transudative malignant effusion were found. Seven of these eight patients had a concomitant disorder known to cause transudative pleural effusion. One patient had fluid overload due to renal failure, and another had been admitted earlier with congestive heart failure. Two patients had definite evidence of deep venous thrombosis, allowing us to postulate pulmonary embolism as a factor contributing to transudation. Three patients had CT evidence of superior vena cava obstruction. Only one patient had no known associations with causes of transudative effusion. CONCLUSION: Malignant pleural effusions were transudative in 5% of our patients. In all except one patient, some evidence suggested the concomitant presence of a transudative state.

Evaluation of the reliability of computed tomographic criteria used in the diagnosis of round atelectasis.

The purpose of this controlled study was to determine the diagnostic accuracy of computed tomography (CT) in the diagnosis of round atelectasis (RA). We reviewed two groups of chest CT scans of 22 patients (with 24 masses). Group 1 scans represent 10 patients (12 masses) known to have RA, and Group 2 scans represent 12 patients with "RA look-alike" masses. Scans in both groups were selected for review by two of the authors and later independently reviewed by the other authors, who were blind to the actual diagnosis. Scans were rated for the presence/absence of 18 features ascribed to RA in the literature and assigned a percent probability of RA by each rater. Consensus was achieved for discordant ratings, and the individual percent probabilities were averaged to create a consensus probability. ROC curve analysis of the consensus percent probability showed that diagnostic accuracy significantly exceeded chance [area under curve (AUC) = 0.95, p < 0.001]. Of all the features of RA examined, the presence of converging bronchovascular markings discriminated best between RA and "RA look-alikes" (sensitivity 83%, specificity 92%, likelihood ratio 11). Presence of adjacent pleural thickening and pleural-based location were even more sensitive features of RA (100% each), but lacked specificity (33 and 67%, respectively; likelihood ratios 3 and 1.5, respectively). We conclude that (a) although the diagnostic accuracy of CT for RA was high in this series, radiographic diagnosis is imperfect and that (b) the presence of converging bronchovascular markings was the best discriminator between the two groups, but that no single CT feature permitted perfect discrimination.

Rare pulmonary manifestation of Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is an inherited disorder of connective tissue with multiple thoracic manifestations. We present an unusual thoracic manifestation of EDS consisting of parenchymal cysts and fibrous and fibroosseous nodules. These manifestations may be related to an abnormal attempt at repair of parenchymal or vascular tears.

The radiographic evaluation of the patient with esophageal carcinoma.

Barium swallow and endoscopy are complementary procedures in the detection of early esophageal carcinoma. CT is useful in the detection of distant metastases, and mediastinal invasion of key structures such as airway, aorta, and pericardium, but does not reliably differentiate T2 from T3 lesions or define subtle upper abdominal adenopathy. The disparity in reported results from different series published over the last 12 years can be accredited to two causes. First is the lack of uniformity in the way the studies were performed. Most authors agree that slice thickness should be 1 cm and contiguous. Lehr et al used 2-cm slices through the upper abdomen with additional slices through areas of special interest. Similarly, Markland defines his technique as "1-cm intervals from the thoracic inlet to the carina and below this at 1.5 cm intervals to the level of the adrenal glands." Such parameters are hardly optimized for the detection of 8-mm lymph nodes. The other cause of the disparity is interobserver variation in study interpretation. Goei et al staged 35 cases of esophageal cancer using CT. The CT interpretations of each of three readers were subsequently correlated with surgical and pathologic findings of 17 patients. CT pathologic correlation of the three observers showed sensitivities ranging from 50% to 57%, specificities ranging from 50% to 60%, and accuracies ranging from 46% to 71%. CT is useful as a surveillance tool in the postoperative patient. MR imaging does not have a defined role in the workup of esophageal tumors at this time.

Pleural changes in malignant pleural effusions: appearance on computed tomography.

BACKGROUND: Tumors metastatic to the pleura are a leading cause of pleural effusions. The computed tomographic (CT) appearance of malignant pleural effusions varies from uniformly low attenuation without pleural abnormalities to thickened, irregular, contrast-enhanced pleura with or without discrete masses. There may be associated changes in the subcostal tissues. OBJECTIVE: To determine the prevalence of abnormalities observed with CT scanning in patients with malignant pleural effusion. METHODS: We analyzed the CT appearance of the pleura in 86 patients with documented malignant pleural effusions. Patients with primary malignancy of the pleura (mesothelioma) were excluded. RESULTS: In 98% of the malignant effusions the fluid was homogeneous. Focal tumor masses were identified within the effusion in 10%. CT evidence of fluid loculation was seen in 40%. Pleural thickening, either smooth or irregular, was identified in 62%. CONCLUSIONS: The transaxial anatomic display afforded by CT scanning facilitates demonstration of several features that should arouse the suspicion of the radiologist and the clinician to the possibility of malignancy involving the pleura.