Imprint cytology in laryngeal and pharyngeal tumours

OBJECTIVE: The aim of this study was to evaluate the role of cytology in providing a reliable diagnosis upon which the clinician can base further investigative or treatment strategies in patients with laryngeal and pharyngeal tumours. METHODS: Imprint cytology diagnoses from 174 patients were correlated with the histological result of a corresponding biopsy. RESULTS: We found that the imprint cytology proved to be a useful, quick and reliable method with complete diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive values of 97%, 96%, 100%, 100% and 92% respectively. CONCLUSION: Imprint cytology allows diagnostic statements in a shorter time than is possible with histological sections and proves a useful adjunct in evaluating laryngeal and pharyngeal lesions. The validity of the method depends on the care with which the specimen is sampled and on the experience of the investigator.     

Endometritis in the mare: a diagnostic study comparing cultures from swab and biopsy

The objective of this study was to compare results from endometrial culture swabs with results from culturing of endometrial biopsies. The culture results were related to cytological findings (polymorphonuclear; PMN-cells) and histological observations (PMN-cells). Biopsy and swab samples were smeared on the surface of a blood agar petri dish, and examined for growth of bacteria. Cytology samples were obtained from endometrial biopsies, stained and examined under microscopy for the presence of PMN-cells. Endometrial biopsies were examined for the presence of PMN-infiltration of the endometrial luminal epithelium and the stratum compactum. Using the presence of PMNs in a tissue specimen as the "best standard" for diagnosing endometritis, the sensitivity of bacterial growth from an endometrial biopsy was 0.82. The sensitivity for cytology was 0.77, and the sensitivity of bacterial growth from an endometrial surface swab was 0.34. The specificity for biopsy cultures, swab cultures, and cytology to diagnose endometritis were 0.92, 1.0, and 1.0 respectively. The positive predictive value for biopsy cultures, swab cultures, and cytology were 0.97, 1.0, and 1.0 respectively. The negative predictive value for biopsy cultures, swab cultures, and cytology were 0.67, 0.44, and 0.62 respectively. In conclusion, bacteriological culture and cytology from an endometrial biopsy provide the practitioner with the most accurate results regarding both sensitivity and positive predictive value.     

Accuracy of touch imprint cytology in diagnosing lung cancer.

A 3-year study assessed the diagnostic accuracy of touch imprint smears in the diagnosis of lung cancer. Touch imprint smears were prepared from 90 computerized tomographic-guided core needle lung biopsies. Cytological diagnosis of touch imprint smears were correlated with the histological diagnosis of the corresponding core needle biopsy specimen, which was taken as the gold standard. The sensitivity, specificity, positive predictive value and negative predictive value of imprint smear results were 89%, 100%, 100% and 68%, respectively. There were no false positives, and all patients with small cell lung cancer were correctly diagnosed with this technique. Imprint cytology can be used to provide a rapid, preliminary diagnosis of lung cancer.     

Role of urinary NMP-22 combined with urine cytology in follow-up surveillance of recurring superficial bladder urothelial carcinoma

OBJECTIVE: To determine efficacy and utility of NMP-22 in follow-up of bladder urothelial carcinoma (UC) and compare NMP-22 as a single evaluating test vs combination with cytology. STUDY DESIGN: Ninety-four consecutive urine cytology samples of bladder UC were identified. Patients received follow-up urine cytology, NMP-22 testing and cystoscopy with surgical biopsy. RESULTS: NMP-22 specificity was 100%, sensitivity 45%, positive predictive value (PPV) 100% and negative predictive value (NPV) 87%. NMP-22 showed lower sensitivity for high-grade lesions and higher for low-grade lesions. Cytologic diagnosis had a high inconclusive rate; when regarded as positive, it resulted in 75% sensitivity, 58% specificity, 33% PPV and 89% NPV. NMP-22 correctly classified 60% of false negative cases diagnosed by cytology with low-grade UC and clarified 27 inconclusive cytologic diagnoses. NMP-22 misclassified 9 cases as false negative, all with high-grade UC; all were correctly identified on cytology as true positive. Combined interpretation showed 90% sensitivity, 92% specificity, 75% PPV and 98% NPV. CONCLUSION: NMP-22 complements cytology by its higher sensitivity for low-grade lesions; its values are not affected by bacillus Calmette Guérin therapy changes, which are limiting in cytology. Combined interpretation of NMP-22 and cytology shows promise as an effective, noninvasive method for surveillance of UC.     

尿液外泌小体中miRNA的含量与肾纤维化的关系

目的:探讨尿液外泌小体(exosomes)中微小RNA(miRNA,miR)的变化与肾纤维化的关系,以寻找早期诊断肾纤维化的生物标志物。方法:以行肾穿刺活检术并诊断为原发性肾脏病的患者为研究对象,其中,肾活检未发现肾纤维化的患者作为对照组,而存在轻到中度肾纤维化的患者作为纤维化组。收集20 m L晨尿,用超速离心方法分离尿液exosomes,用电镜观察其形态,用定量PCR方法检测其中miRNA的含量,并分析其与肾纤维化的关系。结果:超速离心获得的尿液沉淀物呈现exosomes的形态学特征。miR-21、miR-29b、miR-29c、miR-30e、miR-192、miR-200a、miR-200c和miR-429可在所有患者的尿液exosomes中被检出,但含量存在较大差异。与对照组相比,纤维化组患者尿液exosomes中,miR-21、miR-29b、miR-30e和miR-200c的含量显著增高,miR-29c的含量显著下降,而miR-192、miR-200a和miR-429的含量无显著变化。尿液exosomes中miRNA含量与纤维化肾组织中miRNA表达量的变化并不完全一致。结论:尿液exosomes中miR-29c和miR-21的含量在肾纤维化的病变中发生显著改变,可能成为早期诊断肾纤维化的生物标志物。     

Cytomorphologic and immunocytochemical characteristics of reactive renal tubular cells in renal glomerular disease

OBJECTIVE: To investigate the morphologic characteristics and immunocytochemical reaction to vimentin of the reactive renal tubular cells (RRTCs) in renal glomerular disease. STUDY DESIGN: We prospectively evaluated the urine cytology of renal glomerular disease in 40 patients who underwent renal biopsy. The cytology and renal biopsy specimens were analyzed for vimentin immunostaining. RESULTS: A total of 40 urine samples from the 40 patients were cytologically analyzed, and RRTCs were found in 25 samples (25 of 40, 62.5%). These RRTCs showed clear or vacuolated cytoplasm, intracytoplasmic pigmented granules (hemosiderin or lipofuscin) and large nuclei with round to irregular nuclear contours and prominent nucleoli. These cells were seen singly and in acinar clusters. Occasionally RRTCs were embedded in a cast (RRTC cast). Immunocytochemicalstudy revealed RRTCs to be positive for vimentin (25 of 25, 100%). CONCLUSION: Frequently observed characteristic cytomorphologic features of RRTCs included RRTC cast, acinar cluster, vacuolated cytoplasm and intracytoplasmic pigmented granules. A diagnosis of RRTCs can be suggested based on these cytomorphologic features. However, a definitive diagnosis will require immunocytochemical confirmation for vimentin.     

Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast

X. Jing, E. Wey and C. W. Michael Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast Objective: To evaluate the utility of ThinPrep® as an optional specimen processing method for the detection of axillary lymph node metastasis of invasive breast carcinoma. Methods: A computer SNOMED search from the file at our institution between January 2003 and August 2011 retrieved a total of 209 fine needle aspiration (FNA) specimens of axillary lymph nodes prepared by ThinPrep and followed by axillary lymph node biopsy and/or dissection. Original cytological diagnoses and corresponding histological diagnoses were documented. Using the histological diagnoses as the gold standard, the diagnostic parameters including sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and diagnostic accuracy were calculated. Both cytology and histology slides from cyto‐histologically discrepant cases were reviewed. Results: Out of a total of 209 specimens, 193 (92%) had adequate diagnostic material while the remaining 16 specimens (8%) were inadequate for cytological assessment. The diagnostic specimens included 168 invasive ductal carcinomas (IDC), 15 invasive lobular carcinomas (ILC) and 10 mixed carcinomas (IDC and ILC). Excluding 19 cases with malignant cells on FNA in which no residual tumour was found in fibrotic lymph nodes after neoadjuvant therapy (cytology and histology confirmed on review) ThinPrep detected nodal metastasis with an overall sensitivity of 77.5%, specificity of 100%, PPV of 100% and NPV of 53.7%. Diagnostic accuracy was 82.2%. There was no difference in Bloom–Richardson grade or the number or size of metastases between tumours with true‐positive and false‐negative cytology. Sampling error was the sole factor contributing to cyto‐histological discrepancy. Conclusions: ThinPrep is a good alternative to the conventional smear for cytological assessment of axillary lymph node status in patients with invasive breast carcinoma, particularly when specimens are collected at remote sites or when cytologists are not available for assistance during FNA.     

Histology,Protein Clearances,and Response to Treatment in the Nephrotic Syndrome

In a group of 400 nephrotic patients, both adults and children, the histological picture seen on renal biopsy, the selectivity of differential protein clearances, and the response to corticosteroid therapy where applied were studied. The only discernible difference was that of the relative incidence of underlying renal disease; in particular, the much greater incidence of “minimal change” lesions and the near absence of glomerular disease secondary to systemic disorders in children. Highly selective differential protein clearances were strongly associated with response to steroids within eight weeks, and this depended on the relation between this type of protein clearance and the minimal change lesion, which was the only histological appearance associated with complete response to corticosteroid therapy within eight weeks. Neither renal biopsy nor studies of proteinuria allowed prediction of which responding patients would subsequently relapse.Studies of differential protein clearances allow the paediatrician to avoid renal biopsy with safety in nephrotic children aged 1 to 5 years, but cannot distinguish any given renal disease with certainty. Generalized diseases affecting the kidney are usually associated with poorly selective differential protein clearances. Within all groups the most severe changes were usually associated with the least selective differential protein clearances, and vice versa.     

Serum aluminium concentration and aluminium deposits in bone in patients receiving haemodialysis.

Serum aluminium concentrations and biopsy specimens of bone were examined in 56 patients with end stage chronic renal failure receiving maintenance haemodialysis. Deposits of aluminium in bone specimens were often associated with low bone formation with or without osteomalacia. Serum aluminium concentrations of greater than 3.7 mumol/l (10 micrograms/100 ml) indicated a high probability of deposits of aluminium in bone specimens, although high serum concentrations did not predict the type of renal bone disease. Biopsy of the bone is the best method of detecting aluminium intoxication of bone. A serum aluminium concentration of 3.7 mumol/l should be the threshold beyond which bone biopsy should be performed to confirm an overload of aluminium and identify histological bone changes induced by aluminium.     

Validity of the first morning urine collection for screening for microalbuminuria in the diabetic

With the aim of evaluating the reliability of morning urine collection, compared to the overnight period, in the assessment of microalbuminuria, we measured albumin and creatinine concentration in overnight and morning urine of 125 diabetic outpatients. The overnight albumin excretion rate resulted in relation to morning albumin concentration and morning albumin/creatinine ratio. The sensitivity of this method of urine collection, compared to the overnight sample, was 55.5%, the specificity 96.6% and the predictive value 43% using, as a measure, the albumin concentration. These values improved by correcting albumin for creatinine concentration. Concerning high risk albuminuria (overnight excretion rate greater than 30 micrograms/min), we found a sensitivity and predictive value of the first morning collection highly improved by the albumin/creatinine ratio. It is concluded that the first morning urine collection can be used in the diagnosis of microalbuminuria in diabetic patients, especially when we calculate the albumin/creatinine ratio. This simple and reliable method allows the identification of microalbuminuric subjects and of the patients at risk to develop clinical nephropathy with a good sensitivity.     

Culture of Helicobacter pylori: Effect of Preimmersion of Biopsy Forceps in Formalin

Background. Treatment of antibiotic-resistant Helicobacter pylori should be based on bacterial sensitivity testing that requires the ability to isolate the bacterium from gastric mucosal biopsies. The aim of this study was to determine whether the yield for detecting H. pylori infection by culture is reduced by immersion of biopsy forceps in formalin prior to obtaining the specimen.
Materials and Methods. Gastric antral mucosal biopsies (100 specimens) from 50 patients were obtained for culture of H. pylori. An antral biopsy was taken for culture, and with the same forceps a biopsy was taken for histological examination. The biopsy specimen was removed by shaking, whereas the forceps was immersed in 10% buffered formalin for the histological investigation. The forceps was then used without rinsing to obtain a second specimen for culture from an area adjacent to the first site. H. pylori status was determined by histological assessment with the Genta stain and a rapid urease test.
Results. Fifty patients with H. pylori infection documented by histological inquiry and positive rapid urease testing entered the study; 29 had duodenal ulcers, 5 had gastric ulcers, 1 had mucosal associated lymphoid tissue (MALT) lymphoma, and 15 were without ulcer disease. The results of culture both before and after immersion in formalin were identical. One patient had both cultures negative; the sensitivity of culture for detection of H. pylori infection was 98% (95% confidence interval =93%-100%).
Conclusion. Preimmersion of biopsy forceps in formalin does not adversely affect the ability to culture H. pylori.     

Diagnostic sensitivity and specificity of pulmonary cytology: comparison of techniques used in conjunction with flexible fiber optic bronchoscopy

We examined the accuracy of pulmonary cytology in 224 consecutive patients being evaluated for lung cancer. The diagnostic yeild of specimens obtained by various methods, including flexible fiber optic bronchoscopy (FFB), was compared. Among 69 patients with lung cancer, a cytologic diagnosis was made in 87%, including 73% with peripheral tumors. Prebronchoscopy sputa were positive in 50%, bronchial washings in 63%, postbronchoscopy sputa in 82% and bronchial brushings in 59% of the patients. In only one patient was the bronchial brush specimen the only positive cytologic specimen. Normal FFB and small cell undifferentiated cancer were found with increased frequency (P less than 0.05) among the nine patients (13%) with false-negative cytology. Among 155 patients with nonmalignant lung disease, 16 (10%) had false-positive specimens; this finding was significantly related (P less than 0.05) to necrotizing pneumonia in 13 of the 16 patients (81%). The overall diagnostic accuracy of cytology showed 87% sensitivity and 90% specificity, and the predictive value of a positive specimen was 79%. In the absence of necrotizing pneumonia these values exceeded 95%.     

Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate,glomerular filtration rate,and end stage renal failure in chronic renal disease in patients without diabetes.

OBJECTIVE: To evaluate whether the protein:creatinine ratio in spot morning urine samples is a reliable indicator of 24 hour urinary protein excretion and predicts the rate of decline of glomerular filtration rate and progression to end stage renal failure in non-diabetic patients with chronic nephropathy. DESIGN: Cross sectional correlation between the ratio and urinary protein excretion rate. Univariate and multivariate analysis of baseline predictors, including the ratio and 24 hour urinary protein, of decline in glomerular filtration rate and end stage renal failure in the long term. SETTING: Research centre in Italy. SUBJECTS: 177 non-diabetic outpatients with chronic renal disease screened for participation in the ramipril efficacy in nephropathy study. MAIN OUTCOME MEASURES: Rate of decline in filtration rate evaluated by repeated measurements of unlabelled iohexol plasma clearance and rate of progression to renal failure. RESULTS: Protein:creatinine ratio was significantly correlated with absolute and log transformed 24 hour urinary protein values (P = 0.0001 and P < 0.0001, respectively.) Ratios also had high predictive value for rate of decline of the glomerular filtration rate (univariate P = 0.0003, multivariate P = 0.004) and end stage renal failure (P = 0.002 and P = 0.04). Baseline protein:creatinine ratios and rate of decline of the glomerular filtration rate were also significantly correlated (P < 0.0005). In the lowest third of the protein:creatinine ratio (< 1.7) there was 3% renal failure compared with 21.2% in the highest third (> 2.7) (P < 0.05). CONCLUSIONS: Protein:creatinine ratio in spot morning urine samples is a precise indicator of proteinuria and a reliable predictor of progression of disease in non-diabetic patients with chronic nephropathies and represents a simple and inexpensive procedure in establishing severity of renal disease and prognosis.     

Protein creatinine index and Albustix in assessment of proteinuria.

The protein creatinine index in early morning and random urine specimens was compared with the 24 hour urinary excretion of protein in normal subjects and outpatients with abnormal proteinuria. A protein creatinine index (defined as (mg protein/1 divided by creatinine mmol/1) times 10) below 125 in a random specimen excluded abnormal proteinuria, whereas an index of more than 136 indicated the presence of pathological proteinuria. The index for random specimens provided a useful semiquantitative assessment of the 24 hour excretion of protein (mg protein/24 hours), but the index for early morning specimens was less reliable. Errors with Albustix were partly due to intra and inter observer variations in the interpretation of the colour formed when compared with the chart provided. It is proposed that the protein creatinine index on random urine samples should be used to supplement dipsticks in screening for proteinuria in cases where misclassification would be serious.     

Evaluation of reagent strips in detecting asymptomatic bacteriuria in early pregnancy: prospective case series.

OBJECTIVE: To evaluate the performance of reagent test strips in screening pregnant women for asymptomatic bacteriuria at their first visit to an antenatal clinic. DESIGN: Prospective case series. SETTING: Antenatal clinic of a large inner city maternity hospital. SUBJECTS: All women attending for their first antenatal clinic. Patients taking antibiotics for any reason and those with urinary tract symptoms were excluded. INTERVENTION: A midstream urine specimen was divided; half was sent for microscopy and formal bacteriological culture and the other half was tested with a commercial reagent strip test for the presence of blood, protein, nitrite, and leucocyte esterase. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of the reagent strips in diagnosing asymptomatic bacteriuria (defined as 10(5) colony forming units/ml urine). RESULTS: Sensitivity was low, with a maximum of 33% when all four tests were used in combination. Specificity was high, with typical values of 99% or more. Positive predictive value reached a maximum of 69% and negative predictive value was typically 95% or more. CONCLUSION: Urine reagent strips are not sufficiently sensitive to be of use in the screening for asymptomatic bacteriuria and therefore many patients would be missed. In view of the potentially serious sequelae of this condition in pregnant women we recommend that formal bacteriological investigation remain the investigation of choice in this group of patients.     

Germanium in ginseng is low and causes no sodium and water retention or renal toxicity in the diuretic-resistant rats

Ginseng preparations contain high concentrations of germanium (Ge), which was reported to contribute to diuretic resistance or renal failure. However, Ge content in ginseng and the influence on renal functions remain unclear. Forty rats were randomly divided into control group, low, moderate, and high Ge ginseng-treated group and observed for 25 days. Daily urine, renal functions, and serum and urine electrolytics were measured. Ge retention in the organs and renal histological changes were also evaluated. Ge content ranged from 0.007 to 0.450 µg/g in various ginseng samples. Four groups showed no difference in the daily urine output, glomerular filtration rate, urinary electrolytes excretions, 24 h-urine protein, as well as plasma and urine urea nitrogen, creatinine, osmotic pressure, and pH values. Ge did not cause any renal pathological effects in this study. No Na and water retention was detected in the ginseng-treated groups. Ge retention in various organs was found highest in spleen, followed by the kidney, liver, lung, stomach, heart, and pancreas. The total Ge contents in various ginsengs were low, and ginseng treatment did not affect renal functions or cause renal histological changes.     

Comparative Yield of Different Diagnostic Tests for Tuberculosis among People Living with HIV in Western Kenya

Background

Diagnosis followed by effective treatment of tuberculosis (TB) reduces transmission and saves lives in persons living with HIV (PLHIV). Sputum smear microscopy is widely used for diagnosis, despite limited sensitivity in PLHIV. Evidence is needed to determine the optimal diagnostic approach for these patients.

Methods

From May 2011 through June 2012, we recruited PLHIV from 15 HIV treatment centers in western Kenya. We collected up to three sputum specimens for Ziehl-Neelsen (ZN) and fluorescence microscopy (FM), GeneXpert MTB/RIF (Xpert), and culture, regardless of symptoms. We calculated the incremental yield of each test, stratifying results by CD4 cell count and specimen type; data were analyzed to account for complex sampling.

Results

From 778 enrolled patients, we identified 88 (11.3%) laboratory-confirmed TB cases. Of the 74 cases who submitted 2 specimens for microscopy and Xpert testing, ZN microscopy identified 25 (33.6%); Xpert identified those plus an additional 18 (incremental yield = 24.4%). Xpert testing of spot specimens identified 48 (57.0%) of 84 cases; whereas Xpert testing of morning specimens identified 50 (66.0%) of 76 cases. Two Xpert tests detected 22/24 (92.0%) TB cases with CD4 counts <100 cells/μL and 30/45 (67.0%) of cases with CD4 counts ≥100 cells/μl.

Conclusions

In PLHIV, Xpert substantially increased diagnostic yield compared to smear microscopy and had the highest yield when used to test morning specimens and specimens from PLHIV with CD4 count <100 cells/μL. TB programs unable to replace smear microscopy with Xpert for all symptomatic PLHIV should consider targeted replacement and using morning specimens.     

The role of fine needle aspiration cytology in the management of gynecologic malignancies

Between 1978 and 1983, 317 diagnostic fine needle aspirations (FNA) were procured at Indiana University by the Cytology, Radiology or Gynecology services for initial evaluation or follow-up of proven gynecologic malignancies. The primary sites of the neoplasms included the cervix, uterus, ovary, vagina and vulva. Totals of 199 samples were procured from superficial sites, including parametrium, vagina, subcutaneous tissue and superficial lymph nodes, and 118 were obtained from deep soft tissues, abdominal organs, pelvis and deep lymph nodes. Of the FNA specimens, 146 (46%) were cytologically diagnosed as malignant and 171 (54%) were reported as benign. Of the specimens initially given negative diagnoses, 35 (11%) were inadequate samples. No complications occurred as a result of FNA biopsy. All cases were reclassified using strict criteria for an inadequate specimen. After review, 79 biopsies were considered either scant (22%) or inappropriate (0.03%) for the target lesion. Scant specimens were obtained more often in superficial than in deep sites. No significant differences were found in the false-negative rate between superficial and deep sites; all false positives were from superficial sites. The use of strict criteria for adequacy of a sample (two groups of appropriate cells on two separate slides) yielded a specificity of 95%, an increased sensitivity from 73% to 91%, a predictive value for a positive result of 98% and a predictive value for a negative result of 84%. Use of strict criteria for specimen adequacy served to reemphasize two points regarding negative FNA results: that rebiopsy should be suggested and that on-site assessment of the specimen adequacy should be made during the aspiration.