Diffusion-weighted magnetic resonance imaging for assessment of lung lesions: repeatability of the apparent diffusion coefficient measurement.

PURPOSE: To establish repeatability of apparent diffusion coefficients (ADCs) acquired from free-breathing diffusion-weighted magnetic resonance imaging (DW-MRI) in malignant lung lesions and investigate effects of lesion size, location and respiratory motion. METHODS: Thirty-six malignant lung lesions (eight patients) were examined twice (1- to 5-h interval) using T1-weighted, T2-weighted and axial single-shot echo-planar DW-MRI (b = 100, 500, 800 s/mm(2)) during free-breathing. Regions of interest around target lesions on computed b = 800 s/mm(2) images by two independent observers yielded ADC values from maps (pixel-by-pixel fitting using all b values and a mono-exponential decay model). Intra- and inter-observer repeatability was assessed per lesion, per patient and by lesion size (> or <2 cm) or location. RESULTS: ADCs were similar between observers (mean ± SD, 1.15 ± 0.28 × 10(-3) mm(2)/s, observer 1; 1.15 ± 0.29 × 10(-3) mm(2)/s, observer 2). Intra-observer coefficients of variation of the mean [median] ADC per lesion and per patient were 11% [11.4%], 5.7% [5.7%] for observer 1 and 9.2% [9.5%], 3.9% [4.7%] for observer 2 respectively; inter-observer values were 8.9% [9.3%] (per lesion) and 3.0% [3.7%] (per patient). Inter-observer coefficient of variation (CoV) was greater for lesions <2 cm (n = 20) compared with >2 cm (n = 16) (10.8% vs 6.5% ADCmean, 11.3% vs 6.7% ADCmedian) and for mid (n = 14) vs apical (n = 9) or lower zone (n = 13) lesions (13.9%, 2.7%, 3.8% respectively ADCmean; 14.2%, 2.8%, 4.7% respectively ADCmedian). CONCLUSION: Free-breathing DW-MRI of whole lung achieves good intra- and inter-observer repeatability of ADC measurements in malignant lung tumours. KEY POINTS: • Diffusion-weighted MRI of the lung can be satisfactorily acquired during free-breathing • DW-MRI demonstrates high contrast between primary and metastatic lesions and normal lung • Apparent diffusion coefficient (ADC) measurements in lung tumours are repeatable and reliable • ADC offers potential in assessing response in lung metastases in clinical trials.

Pre-operative factors indicating risk of multiple operations versus a single operation in women undergoing surgery for screen detected breast cancer.

We aim to identify preoperative factors at diagnosis which could predict whether women undergoing wide local excision (WLE) would require further operations. 1593 screen-detected invasive and non-invasive breast cancers were reviewed. Age, presence of ductal carcinoma in situ (DCIS), invasive cancer size on mammography, mammographic sign, tumour type, grade and confidence of the radiologist in malignancy were compared. 83%(1315/1593) of women had a WLE. Of these, 70%(919/1315) had a single operation, and 30%(396/1315) multiple operations. These included repeat WLE to clear margins (60%(238/396)), mastectomy (34%(133/396)) and axillary dissection (6%(25/396)). The presence of mammographic microcalcification, lobular carcinoma and grade 2 malignancy on core biopsy were independent risk factors for multiple operations on multivariate analysis. Women with mammographic DCIS >30 mm were 3.4 times more likely to undergo repeat surgery than those with smaller foci. The multidisciplinary team should pay particular attention to these factors when planning surgery.

Image-guided breast biopsy: state-of-the-art.

Percutaneous image-guided breast biopsy is widely practised to evaluate predominantly non-palpable breast lesions. There has been steady development in percutaneous biopsy techniques. Fine-needle aspiration cytology was the original method of sampling, followed in the early 1990s by large core needle biopsy. The accuracy of both has been improved by ultrasound and stereotactic guidance. Larger bore vacuum-assisted biopsy devices became available in the late 1990s and are now commonplace in most breast units. We review the different types of breast biopsy devices currently available together with various localization techniques used, focusing on their advantages, limitations and current controversial clinical management issues.

Prediction of the presence of invasive disease from the measurement of extent of malignant microcalcification on mammography and ductal carcinoma in situ grade at core biopsy.

AIM: To determine whether the extent of microcalcification and ductal carcinoma in situ (DCIS) grade can be used to accurately predict the presence and size of invasive cancer in cases of malignant microcalcification. MATERIALS AND METHODS: Over a 10-year period, 402 cases of malignant microcalcification from an NHS screening programme were analysed. For each case, measurement of mammographic microcalcification extent, DCIS grade, and the presence and size of invasive carcinoma from the excised surgical specimen were recorded. RESULTS: The final histological diagnosis was DCIS only in 71% (284/402) and DCIS with a focus of invasive disease in 29% (118/402). The risk of invasive disease increased with increasing size of microcalcification from 20% (27/136) for cluster size less than 11mm, to 45% (18/40) for cluster size more than 60mm. The risk of invasive disease also increased with increasing histological grade of DCIS from 13% (4/31) with low-grade DCIS to 36% (86/239) with high-grade DCIS. There were significant associations with the presence of invasive disease for cluster size (p=0.0001) and DCIS grade (p=0.003), and when using univariate analysis with simple [cluster size (p=0.01) and grade (p=0.01)] and multiple [cluster size (p=0.02) and grade (p=0.02)] logistic regression, respectively. The Hosmer-Lemeshow goodness-of-fit test suggests that the multiple logistic regression model has a good fit (p=0.99). CONCLUSION: The multidisciplinary team can use these data in individual cases to estimate the risk of invasive cancer and decide whether to carry out an axillary staging procedure.

The relationship of transverse sinus stenosis to bony groove dimensions provides an insight into the aetiology of idiopathic intracranial hypertension.

INTRODUCTION: Transverse sinus tapered narrowings are frequently identified in patients with idiopathic intracranial hypertension (IIH); however, it remains unclear whether they are primary stenoses or whether they occur secondary to raised cerebrospinal fluid pressure. Computed tomographic venography demonstrates both the morphology of the venous system and the adjacent bony grooves so it may provide an insight into the aetiology of these transverse sinus stenoses. MATERIALS AND METHODS: Tapered transverse sinus narrowings (>50%) were studied in 19 patients without IIH and 14 patients with IIH. Computed tomography vascular studies were reviewed and the dimensions of the venous sinuses and bony grooves at the sites of maximum and minimum transverse sinus area dimensions were recorded. RESULTS: There was demonstrated to be a strong correlation of bony groove height with venous sinus height at the largest portions of the transverse sinus in both IIH patients and non-IIH subjects as well as at the transverse sinus narrowing in non-IIH subjects. There was a discordant relationship between bony groove height and venous sinus height at the site of transverse sinus stenoses in IIH patients. In 5/23 IIH transverse sinus stenoses, the bony groove height was proportionate to that seen in non-IIH subjects. There were a further 8/23 cases where the small or absent sinus was associated with an absent bony groove. CONCLUSION: Transverse sinus tapered narrowings in subjects without IIH and in the majority of patients with IIH were associated with proportionately small or absent grooves, and these are postulated to be primary or fixed. Some patients with IIH demonstrate tapered transverse sinus stenoses with disproportionately large bony grooves, suggesting a secondary or acquired narrowing. This implies a varied aetiology for the transverse sinus stenoses of IIH.

Primary angiosarcoma of the ovary: a case report and review of the literature.

INTRODUCTION: Gynecological sarcomas are rare and have a poor prognosis. Uterine sarcomas are most common accounting for 4% of all uterine tumors. Ovarian sarcomas are less frequent and are usually carcinosarcomas. CASE REPORT: A previously healthy 40-year-old G2P2 presented for evaluation of 72 h of right upper quadrant pain and shortness of breath. A malignant right pleural effusion, ascites, and adnexal mass were found. Surgical staging and suboptimal debulking revealed pure angiosarcoma of the ovary Stage IV. DISCUSSION: There are 12 cases of ovarian angiosarcoma reported in the literature. Ten of these cases presented in advanced stages with survivals of 2-30 months. Various chemotherapy regimens have been tried on these tumors including the most recent recommendation of MAID (mesna, doxorubicin, ifosfamide, and dacarbazine) and prognosis remains poor. Our patient underwent elective right pleurodesis via video-assisted thorascopic surgery under local anesthesia for an early recurrent right pleural effusion and subsequently began MAID chemotherapy.

Impact of interruptions and distractions on dispensing errors in an ambulatory care pharmacy.

A possible association between interruptions and distractions and the occurrence of dispensing errors was investigated. Fourteen pharmacists and 10 technicians in an ambulatory care pharmacy at a general medical-surgical hospital were tested for distractibility by using the group embedded figures test (GEFT) as well as for visual acuity and hearing. They were videotaped as they filled prescriptions during a 23-day period in 1992. A study investigator compared each filled prescription with the physician's written order, noted details of deviations, verified with the pharmacist any errors that occurred, and asked the pharmacist to correct the error if necessary. Interruptions and distractions were detected and characterized by reviewing the videotapes. None of the study participants had significant hearing or visual impairment. There was a significant association between GEFT scores and error rates. A total of 5072 prescriptions were analyzed, and 164 errors were detected, for an overall error rate of 3.23%. Wrong label information was the most common type of error (80% of errors detected). A total of 2022 interruptions (mean +/- S.D. per half hour per subject, 2.99 +/- 2.70) and 2457 distractions (mean +/- S.D. per half hour per subject, 3.80 +/-3.17) were detected. The error rate for sets of prescriptions with one or more interruptions was 6.65% and for sets during which there were one or more distractions, 6.55%. Interruptions and distractions per half hour were both significantly associated with errors. In an ambulatory care pharmacy, interruptions and distractions over a half-hour period were associated with dispensing errors, a majority of which involved incorrect label information.

Papillary and follicular thyroid carcinoma metastatic to the skin: a case report and review of the literature.

Cutaneous metastases from thyroid cancers are rare. We report the case of an otherwise asymptomatic 81-year-old woman with an enlarging scalp lesion. Her solitary skin metastasis was the presenting feature of thyroid carcinoma. Routine histopathology of the lesion was notable for an atypical clear cell neoplasm. Immunohistochemistry was positive for thyroglobulin. Subsequent resection of the thyroid gland identified separate foci (< 1 cm) for both papillary and follicular carcinoma. Although such immunohistochemical staining has been used previously, it has never been reported to provide the definitive diagnosis for a solitary cutaneous metastasis from the thyroid. Previous tumors had anatomic features in a clinical context that permitted identification by routine light microscopy. Clear cell features found in the follicular focus of carcinoma in the thyroid suggest that it is the primary. A worldwide literature review reveals that follicular carcinoma has a greater preponderance than papillary carcinoma for cutaneous metastasis and that the majority of skin metastases from either papillary or follicular thyroid cancer are localized to the head and neck.

Observational study of accuracy in compounding i.v. admixtures at five hospitals.

Rates of errors in i.v. admixture compounding at five U.S. hospital pharmacies were studied. Pharmacy staff members at five hospitals representing each U.S. geographic region were observed as they compounded sterile products in order to record the medication, dose, base solution, and other details. Intravenous admixtures, antineoplastic preparations, parenteral nutrient solutions, and ready-to-use products were included. Observations took place for five days at each pharmacy. The observers' notes were checked against the labels used to prepare the doses; any deviation was considered an error. The clinical importance of each error was assessed for its potential to affect a patient adversely. The mean error rate for the five hospitals combined was 9% (145 errors for 1679 doses), excluding ready-to-use products. Mean error rates for individual pharmacies ranged from 6% to 10%. Wrong-dose errors were the most common type of error. Parenteral nutrient solutions had the highest error rates-37% for manual preparation and 22% for preparation that was partly automated. Of every 100 errors, 2 were judged to be potentially clinically important. In five U.S. hospital pharmacies, the observed error rate for compounding i.v. admixtures was 9%.

Inferior rectus recession--an effective procedure?

AIMS: To examine the postoperative stability of inferior rectus recession, with particular reference to the incidence of progressive overcorrection. METHODS: The results of consecutive patients undergoing inferior rectus recession over a 3 year period were reviewed. RESULTS: 21 patients underwent inferior rectus recession, using an adjustable suture technique in all but three cases. In 16 patients additional vertical muscle surgery was performed at the time of the inferior rectus recession. All patients were followed for a minimum of 3 months postoperatively, with a mean follow up of 9.3 months. At the final postoperative visit 11 patients were well aligned, eight were undercorrected, and two were overcorrected. In five of the eight undercorrected cases, the residual deviation was the result of postoperative drift in the direction of the preoperative deviation, following an initially good alignment. Review of the results failed to reveal any factor predictive for this postoperative drift. CONCLUSION: The risk of postoperative overcorrection following inferior rectus recession should be considered, but in this study, undercorrection occurred more frequently than overcorrection. The possible reasons for overcorrection and undercorrection are discussed.

Relationships between ambient sounds and the accuracy of pharmacists' prescription-filling performance.

Associations between ambient sounds and accuracy of pharmacists' prescription-filling performance in a pharmacy was studied. Pharmacists were videotaped as they filled prescriptions each workday for 23 days. Each filled prescription was inspected by the investigator. Deviations from the physician's written order were considered errors. Videotape analysis was used to detect unpredictable, predictable, uncontrollable, and controllable sounds. A within-subjects case control study design was employed to determine whether the frequency of ambient sounds was significantly different when prescriptions with errors, compared with those without errors, were filled. Loudness, in terms of equivalent sound levels (Leq) for each half hour, was analyzed for a relationship to dispensing error rate. A mean dispensing error rate of 3.23% was found. Unpredictable sounds, controllable sounds, and noise had a significant effect on pharmacists which resulted in a decreased dispensing error rate. These results suggest that the quality of pharmacists' performance is not adversely affected by ambient sound. As equivalent sound levels increased, the error rate increased to a point, then decreased.

Re-engineering a pharmacy work system and layout to facilitate patient counseling.

The development and evaluation of a new work system and facility design for a chain of community pharmacies are described. A new work system was developed to optimize utilization of pharmacist and technician time and allow the pharmacy to increase patient counseling without adding personnel. In the new system, pharmacists would review prescriptions, check technicians' work, and dispense prescriptions, counseling patients as needed; technicians would enter prescriptions into the pharmacy computer and fill them. The existing work system and design were evaluated in June and July of 1992 by observing, classifying, and recording activities of pharmacy personnel three days per week at six pharmacies in the chain. Pharmacy designs that would work with the new work system were created by a university design class after consultation with representatives of the pharmacy chain and the university's college of pharmacy. The pharmacy chain selected one design, and a detailed floor plan and specifications were created. To test how the new design and system would work at each of the six test pharmacies, a computer simulation program was developed and verified by using the data collected on the existing pharmacy operations. Computer simulation showed that, with the new design and system, increasing patient counseling would increase patient waiting time slightly but would not require additional personnel. The layout and work system in a chain of community pharmacies were redesigned to facilitate patient counseling and make the best use of employee time.

Sequential mast cell infiltration and degranulation during experimental carcinogenesis.

Mast cell density, distribution, and ultrastructure were studied by light and electron microscopy in hamster buccal pouches undergoing chemically induced carcinogenesis. Epidermoid carcinomas in the pouches were induced by three topical applications per week of 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) in oil using a brush. Four experimental, DMBA-treated and two normal, untreated hamsters were sacrificed after 8, 10, 12, 14, and 16 weeks. After 8 weeks of DMBA treatment, the epithelium showed the pathological signs of dysplasia and hyperkeratosis. In the dermis an increased number of mast cells were evident, some of which showed degranulation. A few mast cells had started to migrate upwards towards the dysplastic epithelium after 10 weeks of DMBA treatment. Rapid degranulation was also apparent in some mast cells. These processes of upward migration and degranulation continued progressively during the 12- and 14-week periods of DMBA application in correlation with the progression of the tumor. By 16 weeks of treatment with the carcinogen, more mast cells had migrated closer to the invasive carcinoma, and many had degranulated. In the connective tissue mast cells were fully packed with many granules, and some mast cells were in proximity to macrophages and eosinophils. Our observations demonstrate that there is a positive correlation between developing carcinomas and mast cell density. Mast cell migration towards the carcinoma and degranulation were also evident.

Effect of estradiol on ultrastructure of granular ducts in submandibular glands of female rats.

The effects of estradiol on the granular ducts in submandibular glands of female albino rats were studied. Twenty-five-milligram pellets of 17 beta-estradiol were implanted subcutaneously in the experimental animals, and their glands, as well as controls, were examined after 2, 4, 7, and 10 wk using light and electron microscopy. During the course of the experiment an increasing proportion of the granules in the granular ducts appeared more lightly stained in the experimental animals. In the estradiol-treated rats the granular ducts increased in relative cross-sectional area at a faster rate than in the controls, which exhibited maturation changes. In addition, the average number of granules per granular duct cell decreased significantly in the treated animals. Our results indicate that estradiol caused a change in the cytology of the granular ducts suggesting an alteration in protein synthesis. These results might occur through a change in structural proteins or in other hormones and growth factors which are known to influence the submandibular gland.

Autophagocytosis of melanosomes in cultured embryonic retinal pigment cells.

Autophagocytosis not only accounts for the early pigment loss found in proliferating cultured retinal pigment cells, but also occurs in slowly growing and in non-proliferating cells. Both melanosome synthesis and destruction may take place concurrently in cells. Autophagosomes may contain both fully formed melanosomes and also premelanosomes in various stages of formation, are positive for lysosomal enzyme activity, and likely represent secondary lysosomes.

Ultrastructure of normals and castrates and the effects of testosterone and ultraviolet (UVL-B) irradiation on scrotal skin of rats.

The ultrastructure of the testosterone dependent epidermal melanocyte system of the scrotal skin of normals and castrates, with and without testosterone replacement therapy, and UVL-B (280-315 nm) radiation in black Long Evans rats is reported. UVL-B increases melanocyte activity, melanosome forming apparatus, (size of Golgi zone and RER, and quantity of cytoplasmic vesicles, dendrites, and stages of melanosomes) in normals and in castrates. Testosterone replacement therapy to castrates is not a prerequisite for stimulation by UVL-B, but it enhances the effects of UVL-B without restoring normalcy as melanosome packaging into complexes predominates. After UVL-B stimulation of normals or castrates, melanocyte dendrites are observed more often. Melanocyte dendrites of skin of castrated rats are observed less often than in normals, but with testosterone replacement therapy, the dendrites become more numerous. Melanosomes donated to keratinocytes are mostly located as singles in normals and as complexes in castrates. After UVL-B, castration, or testosterone replacement therapy, the melanosomes are packaged in keratinocytes in complexes larger than in normals. In the epidermis of long term castrates (9-109 days), non-specific clear cells are observed and Langerhans cells containing melanosomes; we did not observe them in normals. Melanocytes of castrates have a reduced melanosome forming apparatus. The dermis of castrates contains many dermal melanocytes in the superficial dermis with melanosomes in several stages of formation. These cells are not apparent in normals at this location in the dermis. Testosterone replacement therapy and/or UVL-B administered to castrates does not restore the epidermal melanocyte system nor the dermis to precastration ultrastructural appearance; castration has a permanent altering effect as melanosomes are packaged into complexes.