Single Needle Biopsy Research Articles

Value of synthetic MRI quantitative parameters in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate.

Transrectal ultrasonography (TRUS)/magnetic resonance imaging (MRI) fusion-guided biopsy has a high clinical application value. However, this technique has some limitations, which limit its use in routine clinical practice. Therefore, the selection of suitable proatate lesions for this technique is worthy of our attention. Synthetic MRI (SyMRI) is capable of quantifying multiple relaxation parameters, which might have potential value in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate. The aim of our study is to examine the value of SyMRI quantitative parameters in preprocedural evaluation for TRUS/MRI fusion-guided biopsy of the prostate. We prospectively selected 148 lesions in 137 patients who underwent prostate biopsy in our hospital. Next, 2-4 needles of TRUS/MRI fusion-guided biopsy combined with 10 needles of system biopsy(SB) were used as the protocol for prostate biopsy. Before biopsy, the MAGiC sequences of the MRI images of the enrolled patients underwent post-processing, and the longitudinal relaxation time (T1), transverse relaxation time (T2), and proton density (PD) were extracted. The biopsy pathology results were used as a gold standard to compare the differences in SyMRI quantitative parameters between benign and malignant prostate lesions in the peripheral and transitional zones. The receiver operating characteristic (ROC) curves were plotted to confirm the optimal SyMRI quantitative parameter for prostate lesion benignancy/malignancy performance, and the cutoff values of these parameters were used for grouping the lesions. The single-needle biopsy prostate cancer (PCa)-positivity rates (number of positive biopsy needles/total biopsy needles) and PCa overall detection rates by TRUS/MRI fusion-guided biopsy and SB were compared in different subgroups. The T1 and T2 values can determine the benignancy/malignancy of prostate transition lesions(p < 0.01), and the T2 value has a greater diagnostic performance (p = 0.0376). The T2 value can determine the benignancy/malignancy of prostate peripheral lesions. The optimal diagnostic cutoff values for T2 were 77 and 81 ms, respectively. The single-needle PCa positivity rate of TRUS/MRI fusion-guided biopsy was higher than SB for any prostate lesions in different subgroups (p < 0.01). However, only in the subgroup of transition zone lesions with T2 ≤ 77 ms, the PCa overall detection rate of TRUS/MRI fusion-guided biopsy was significantly higher than that of SB (p = 0.031). SyMRI-T2 value can provide a theoretical basis for the selection of suitable lesions for TRUS/MRI fusion-guided biopsy.

Estimating Nephron Number from Biopsies: Impact on Clinical Studies.

Accumulating evidence supports an association between nephron number and susceptibility to kidney disease. However, it is not yet possible to directly measure nephron number in a clinical setting. Recent clinical studies have used glomerular density from a single biopsy and whole kidney cortical volume from imaging to estimate nephron number and single nephron glomerular filtration rate. However, the accuracy of these estimates from individual subjects is unknown. Furthermore, it is not clear how sample size or biopsy location may influence these estimates. These questions are critical to study design, and to the potential translation of these tools to estimate nephron number in individual subjects. We measured the variability in estimated nephron number derived from needle or virtual biopsies and cortical volume in human kidneys declined for transplantation. We performed multiple needle biopsies in the same kidney, and examined the three-dimensional spatial distribution of nephron density by magnetic resonance imaging. We determined the accuracy of a single-kidney biopsy to predict the mean nephron number estimated from multiple biopsies from the same kidney. A single needle biopsy had a 15% chance and virtual biopsy had a 60% chance of being within 20% of the whole-kidney nephron number. Single needle biopsies could be used to detect differences in nephron number between large cohorts of several hundred subjects. The number of subjects required to accurately detect differences in nephron number between populations can be predicted on the basis of natural intrakidney variability in glomerular density. A single biopsy is insufficient to accurately predict nephron number in individual subjects.

Technical Feasibility and Safety of Repeated Computed Tomography–Guided Transthoracic Intratumoral Injection of Gene-Modified Cellular Immunotherapy in Metastatic NSCLC

IntroductionTo assess the technical feasibility and safety of repeated percutaneous computed tomography (CT)–guided transthoracic biopsies and intratumoral injections of gene-modified dendritic cells in metastatic NSCLC. MethodsA total of 15 patients with 15 NSCLC lesions measuring greater than 1.0 cm underwent two cycles of intratumoral biopsies and CCL21 dendritic cell injections separated by 7 days. All needle placements and injections were done under CT guidance. Clinical and imaging follow-up was done approximately 4 weeks after the first procedure. Safety and feasibility were determined as: (1) safety and feasibility similar to that of single-needle biopsy, and (2) an absence of serious adverse events defined as grade greater than or equal to three according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. ResultsA total of 30 percutaneous, transthoracic intratumoral biopsies and injections into the lung cancer were performed, two cycles (at d 0 and 7) received by each patient (311 biopsies and 96 intratumoral injections). All percutaneous cases achieved technical success with respect to needle placement for both biopsy and injection of CCL21 dendritic cells. Only minor complications were observed (grade <3), including pneumothorax (n = 10, 33%) and small postbiopsy hemorrhage (n = 2, 7%). Pneumothorax was moderate (n = 1) or trace (n = 9), with resolution of the moderate pneumothorax after manual aspiration without chest tube placement. No patient required chest tube placement. No other complications or serious adverse effects related to the biopsy or dendritic cell injection were noted. All patients were in stable condition after up to 4 hours in the recovery unit and were discharged home on the same day. No procedure-related complications were observed on imaging or clinical follow-up at 4 weeks. ConclusionsRepeated percutaneous, transthoracic CT-guided biopsies and intratumoral gene-modified cell-based immunotherapy injections into lung cancers are technically feasible, safe, and reproducible. There were no procedure-related serious (defined as grade ≥3) adverse events.

Genomic Heterogeneity and the Small Renal Mass

Purpose: Tumor heterogeneity may represent a barrier to preoperative genomic characterization by needle biopsy in clear cell renal cell carcinoma (ccRCC). The extent of heterogeneity in small renal tumors remains unknown. Therefore, we set out to evaluate heterogeneity in resected large and small renal tumors.Experimental Design: We conducted a study from 2013 to 2016 that evaluated 47 consecutive ccRCC tumors resected during radical or partial nephrectomy. Cases were designated as small (<4 cm) and large (>7 cm) tumors. Each tumor had three regions sampled. Copy-number variation (CNV) was assessed and gene expression analysis was performed to characterize the clear-cell A and B (ccA/ccB) profile and the cell-cycle progression (CCP) score. Genomic heterogeneity between three regions was evaluated using CNV subclonal events, regional expression profiles, and correlation between gene expression.Results: Twenty-three small and 24 large tumors were analyzed. Total CNVs and subclonal CNVs events were less frequent in small tumors (P < 0.001). Significant gene expression heterogeneity was observed for both CCP scores and ccA/ccB classifications. Larger tumors had more variance in CCP scores (P = 0.026). The distribution of ccA/ccB differed between small and large tumors with mixed ccA/ccB tumors occurring more frequently in the larger tumors (P = 0.024). Analysis of five mixed tumors (with both ccA/ccB regions) demonstrated the more aggressive ccB phenotype had greater CNV events (P = 0.014).Conclusions: Small renal tumors have much less genomic complexity and fewer subclonal events. Pretreatment genomic characterization with single-needle biopsy in small tumors may be useful to assess biologic potential and may influence therapy. Clin Cancer Res; 24(17); 4137-44. ©2018 AACR.

Colorectal Cancer Genetic Heterogeneity Delineated by Multi-Region Sequencing.

Intratumor heterogeneity (ITH) leads to an underestimation of the mutational landscape portrayed by a single needle biopsy and consequently affects treatment precision. The extent of colorectal cancer (CRC) genetic ITH is not well understood in Chinese patients. Thus, we conducted deep sequencing by using the OncoGxOne™ Plus panel, targeting 333 cancer-specific genes in multi-region biopsies of primary and liver metastatic tumors from three Chinese CRC patients. We determined that the extent of ITH varied among the three cases. On average, 65% of all the mutations detected were common within individual tumors. KMT2C aberrations and the NCOR1 mutation were the only ubiquitous events. Subsequent phylogenetic analysis showed that the tumors evolved in a branched manner. Comparison of the primary and metastatic tumors revealed that PPP2R1A (E370X), SETD2 (I1608V), SMAD4 (G382T), and AR splicing site mutations may be specific to liver metastatic cancer. These mutations might contribute to the initiation and progression of distant metastasis. Collectively, our analysis identified a substantial level of genetic ITH in CRC, which should be considered for personalized therapeutic strategies.

2131 DEVELOPMENT AND VALIDATION OF THE BIOPSY-BASED GENOMIC PROSTATE SCORE (GPS) AS A PREDICTOR OF HIGH GRADE OR EXTRACAPSULAR PROSTATE CANCER TO IMPROVE PATIENT SELECTION FOR ACTIVE SURVEILLANCE

25% at 5 and 10 years post RP. The GC had a c-index of 0.79 (95% CI 0.71-0.86) for predicting metastasis and this was significantly better than any single clinical variable (c-indices: 0.49 0.65). Decision curve analysis showed that the GC model had higher overall net benefit compared to clinical variables over a wide range of ?decision-to-treat? thresholds for risk of metastasis. In multivariable modeling with clinicopathologic variables, GC remained the only significant independent predictor of metastasis (HR 1.51, for each 0.1 unit increment p 0.001). CONCLUSIONS: Our results suggest that GC can better predict metastatic disease progression compared with clinical variables and may help identify both patients at higher risk to progress and those more likely to have an indolent course. This may enable optimization of multimodal therapy for high risk prostate cancer patients.

Impact of pre‐treatment prostate tissue androgen content on the prediction of castration‐resistant prostate cancer development in patients treated with primary androgen deprivation therapy

Great advances in tissue androgen analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) have made it possible to evaluate the tissue androgen content from a single needle prostate biopsy specimen. In this study, we investigated if pre-treatment androgen content in prostate biopsy specimens could predict their response to primary androgen deprivation therapy (ADT) and future castration-resistant prostate cancer (CRPC). One-hundred and sixty-five prostate cancer patients who received primary ADT were enrolled. They had received multiple core prostate needle biopsy at diagnosis, and an additional one needle biopsy specimen was obtained for tissue androgen determination using LC-MS/MS. The patients' prostate specific antigen (PSA) values were periodically followed during the treatment and patients were determined to have CRPC when their PSA value increased continuously to 25% above the nadir and a 2.0ng/mL increase. A significant correlation was found between PSA value decline velocity (PSA half-time) after ADT and pre-ADT tissue androgen content. Twenty-three patients were determined to have CRPC. These CRPC patients had a significantly high concentration of tissue T (p<0.01) and low concentration of tissue 5α-dihydrotestosterone (DHT) (p<0.01), resulting in a higher tissue T/DHT ratio (p<0.001). A multivariate Cox proportional hazard model revealed the pre-ADT tissue T/DHT ratio and Gleason score as independent predictors for CRPC development. By using the two statistically significant variables, the relative risk of CRPC development could be calculated. The results of this study suggest that the evaluation of prostate androgen content in a single needle biopsy specimen may be useful to predict future CRPC development after primary ADT. Further studies are required for the clinical application of T/DHT ratio evaluation.

Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers

The mutation pattern of breast cancer molecular subtypes is incompletely understood. The purpose of this study was to identify mutations in genes that may be targeted with currently available investigational drugs in the three major breast cancer subtypes (ER+/HER2-, HER2+, and Triple Negative). We extracted DNA from fine needle aspirations of 267 stage I-III breast cancers. These tumor specimens typically consisted of >80% neoplastic cells. We examined 28 genes for 163 known cancer-related nucleic acid variations by Sequenom technology. We observed at least one mutation in 38 alleles corresponding to 15 genes in 108 (40%) samples, including PIK3CA (16.1% of all samples), FBXW7 (8%), BRAF (3.0%), EGFR (2.6%), AKT1 and CTNNB1 (1.9% each), KIT and KRAS (1.5% each), and PDGFR-α (1.1%). We also checked for the polymorphism in PHLPP2 that is known to activate AKT and it was found at 13.5% of the patient samples. PIK3CA mutations were more frequent in estrogen receptor-positive cancers compared to triple negative breast cancer (TNBC) (19 vs. 8%, p=0.001). High frequency of PIK3CA mutations (28%) were also found in HER2+ breast tumors. In TNBC, FBXW7 mutations were significantly more frequent compared to ER+ tumors (13 vs. 5%, p=0.037). We performed validation for all mutated alleles with allele-specific PCR or direct sequencing; alleles analyzed by two different sequencing techniques showed 95-100% concordance for mutation status. In conclusion, different breast cancer subtypes harbor different type of mutations and approximately 40 % of tumors contained individually rare mutations in signaling pathways that can be potentially targeted with drugs. Simultaneous testing of many different mutations in a single needle biopsy is feasible and allows the design of prospective clinical trials that could test the functional importance of these mutations in the future.

Citation for a discussion of noncompliance

Dr. Larry Covelli was proud of the IACUC he chaired at Great Eastern University. There was a culture of thorough but reasonable protocol reviews, open discussions at meetings and an honest effort to balance animal welfare with research requirements. Why, then, was he morose and bitter after talking to the IACUC Administrator? Unknown to the IACUC, an investigator without an IACUC protocol was given a single-needle biopsy sample taken from the liver of a sheep that was being used in a survival abdominal surgical procedure for an unrelated purpose. The sheep study did have IACUC approval, but the approval did not include the biopsy. The Principal Investigator (PI) of the sheep study thought he was just doing a favor for a colleague who needed a small sample of liver tissue. In fact, as was later learned, the PI thought he was reducing animal usage because his colleague would not have to use an entirely separate animal for the biopsy. As for the sheep, she recovered uneventfully. All of this occurred on a Monday, and by the next morning, Covelli knew of the incident. He quickly contacted both investigators, told them why they were noncompliant with NIH/OLAW policy and USDA/Animal Care regulations, and stated that no further biopsies were to be done without an approved protocol amendment or a new protocol. Coincidentally, the monthly IACUC meeting took place that Wednesday, and at the meeting, Covelli dutifully reported what had transpired. After a discussion, the committee concluded that the actions taken by Covelli were appropriate and voted to send a letter of explanation and reprimand to both investigators. Although the incident was a protocol noncompliance, the discussion and vote indicated it was not serious enough to inform NIH/OLAW of the incident and its resolution. Some months later, during a routine USDA/Animal Care inspection, the inspecting veterinarian read the minutes of the IACUC meeting during which the sheep

Micro-Sieving: Isolation of Whole Glomeruli from a Single Renal Needle Biopsy Sample

Renal biopsy samples are important not only for the diagnosis of glomerulonephritis, but also for the investigation of its pathogenesis. However, it remains difficult to biochemically analyze proteins extracted solely from the glomeruli of needle biopsy samples, since the samples contain various components like renal tubules and connective tissue. Even a recent micro-dissection method, recovering the glomeruli in the sliced sections of the biopsy samples, has not fully solved the difficulty because the amount of obtainable proteins by this method is not usually enough for protein analysis. To overcome this problem, we established a simple but reliable method to isolate whole glomeruli from needle biopsy samples. By this method, termed ‘micro-sieving’, we were able to isolate on average more than 50 glomeruli from a single needle biopsy sample in an hour. The amount of the extracted glomerular proteins was on average 23 µg per biopsy sample. As a representative use of this method, we were able to obtain a glomerular protein profile by fluorescent 2-dimensional electrophoresis for each of the tested patients with glomerulonephritis. ‘Micro-sieving’ can be used widely as a fundamental technique to analyze glomeruli in renal needle biopsy samples.

Preparation of a Single Prostate Needle Biopsy Specimen for Histological Diagnosis and RNA Analysis

When a prostate needle biopsy specimen is used for molecular study, a second specimen from the same area as the first one has previously been required for pathological diagnosis. However, we developed a method for obtaining substances such as RNA and we also made pathological diagnosis possible from a single needle biopsy specimen, improving reliability. Prostate needle biopsy specimens from 118 patients were frozen in optimal cutting temperature compound. Tissue from the upper part of the frozen specimen was sectioned longitudinally for histopathological examination. The remainder of the specimen was placed in TRIzol reagent to extract total RNA for molecular biological investigation. Pathological diagnosis and total RNA extraction (1.6 to 32.7 microg) could be obtained from 1 needle biopsy specimen. When 2 specimens were obtained from the same area of the prostate, pathological diagnoses were discordant in 19% of the cases. We established a method for histopathological diagnosis in the prostate needle biopsy specimen used for molecular investigation. This single specimen method may facilitate molecular research in prostate cancer.

Diagnosis of prostatic inflammation: Efficacy of needle biopsies versus tissue blocks

Objectives To assess the variation of inflammation found on single needle biopsies, we compared our results using multiple needle biopsies and surgical samples taken from predetermined areas of prostates removed from patients with prostate cancer. Methods Biopsies and tissue blocks were taken from 25 prostates that had been removed at prostate cancer surgery. These samples were taken from the contralateral side from the cancer whenever possible. The biopsies were taken from the apex, middle, and base, and blocks were taken from the peripheral and transition zones of the middle region. The biopsies were evaluated for density of inflammatory cells and their histologic location (glandular vs. periglandular vs. stromal). Results Inflammation was generally periglandular, with multifocal and diffuse patterns. The severity of the inflammation was quite variable. The overall inflammatory cell counts did not differ among the regions except for lower levels at the base. Correlation coefficients demonstrated significant correlations of the middle region biopsies with the peripheral zone and transition zone blocks ( P = 0.02 and P = 0.016); the apical biopsies also correlated with the transition zone blocks. Conclusions Our results suggest that individual, transrectal needle biopsies taken consistently from the peripheral zone or transition zone of the apex or middle region of prostates from patients with incidental prostatitis may serve as well as multiple biopsies for evaluating the degree of inflammation.

Metastatic renal cell carcinoma: CT-guided immunotherapy as a technically feasible and safe approach to delivery of gene therapy for treatment.

To assess the technical feasibility and safety of weekly outpatient percutaneous computed tomographic (CT)-guided intratumoral injections of interleukin-2 (IL-2) plasmid DNA in a wide variety of superficial and deep tumor sites. Twenty-nine patients with metastatic renal cell carcinoma and a total of 30 lesions measuring 1.0 cm(2) or greater in accessible thoracic (n = 15) or abdominal (n = 15) locations underwent up to three cycles of six weekly intratumoral IL-2 plasmid DNA injections. CT was used to guide needle placement and injection. After injection cycle 1, patients whose tumors demonstrated stable (< or =25% increase and < or =50% decrease in product of lesion diameters) or decreased size (>50% decrease in product of lesion diameters) advanced to injection cycle 2. Patients whose lesions decreased in size by more than 50% over the course of injection cycle 2 were eligible to begin injection cycle 3. An acceptable safety and technical feasibility profile for this technique was deemed to be (a) a safety and feasibility profile similar to that of single-needle biopsy and (b) an absence of serious adverse events (as defined in Title 21 of the Code of Federal Regulations) and/or unacceptable toxicities (as graded according to the National Cancer Institute Common Toxicity Criteria). A total of 284 intratumoral injections were performed, with a mean of 9.8 injections (range, 6-18 injections) received by each patient. Technical success (needle placement and injection of gene therapy agent) was achieved in all cases. Complications were experienced after 42 (14.8%) of the 284 injections. The most common complication was pneumothorax (at 32 [28.6%] of 112 intrathoracic injections), for which only one patient required catheter drainage. Complications occurred randomly throughout injection cycles and did not appear to increase as patients received more injections (P =.532). No patient experienced serious adverse events or unacceptable toxicities. Percutaneous CT-guided intratumoral immunotherapy injections are technically feasible and can be safely performed.

The percutaneous needle biopsy is safe and recommended in the diagnosis of musculoskeletal masses.

The purpose of this study was to analyze the role of percutaneous core needle biopsy in the diagnosis of musculoskeletal sarcomas. One hundred eighty-five biopsy procedures were performed on 161 musculoskeletal tissue masses suspected of being a sarcoma in 155 patients who underwent subsequent tumor resection. A percutaneous core needle biopsy was performed on all masses either in the clinic or under radiologic guidance. If an adequate diagnosis could not be made on the basis of this biopsy specimen, an open incisional biopsy was performed. One hundred seventy-three core needle biopsy procedures were performed: 90 without radiologic guidance, 55 computed tomography guided, and 28 fluoroscopically guided. Twelve open incisional biopsies were performed. Eighty-three sarcomas, 67 benign mesenchymal tumors, and 11 metastatic epithelial tumors were identified. Analysis of the data reveals that only 7.4% of the masses required open biopsy. In 88.2% of the masses, a single percutaneous biopsy procedure was adequate, and no additional biopsy was necessary. There was a 1.1% rate of complications; none caused a change in the patient's treatment plan. There was a 1.1% rate of major diagnostic errors, none of which ultimately impacted on the patient's outcome. There were no unnecessary amputations. Percutaneous needle biopsy showed a positive predictive value of 100%, a negative predictive value of 82%, a sensitivity of 81.8%, and a specificity of 100%. The accuracy of a single-needle biopsy procedure to identify benign versus malignant lesions, exact grade, and exact pathology was 92.4%, 88.6%, and 72.7%, respectively. The percutaneous needle biopsy was found to be extremely effective and safe for the diagnosis of musculoskeletal masses. This method allowed 88% of patients with suspected sarcomas to undergo a single-needle biopsy procedure before the initiation of definitive treatment. Patients undergoing percutaneous needle biopsy had lower rates of major diagnostic errors and complications than previously described for open biopsy. Open biopsy offered limited additional information when preceded by a needle biopsy, given that these tumors were difficult to identify even after final resection.

The association of selected pathological features with prostate cancer in a single-needle biopsy accession

Isolated high-grade prostatic intraepithelial neoplasia (PIN) has been shown to be a positive predictor of prostate cancer (PCa) on follow-up biopsy. However, the incidence of isolated high-grade PIN in needle biopsy specimens has been reported with a highly variable frequency of 1% to 15%. The current study examined the relationship of various pathological features with PCa on a single biopsy accession. A study population of 388 community-based consecutive needle biopsy accessions was prospectively recorded by a single pathologist (T.M.W.). All of the individual biopsy specimens were coded for the presence of PCa, high-grade PIN, low-grade PIN, chronic inflammation (CI), intraluminal prostatic crystalloids (IPC) in benign glands, and mucinous metaplasia (MM). One hundred twenty-nine (33%) of the patients were diagnosed with PCa. The 8% incidence of isolated high-grade PIN was consistent with previous studies. The incidence of other pathological features were as follows: high-grade PIN, 14%; low-grade PIN, 13%; CI, 30%; IPC, 4%; and MM, 8%. Of the patients with high-grade PIN, 47% had PCa on a separate core biopsy, whereas 31% of patients without high-grade PIN were observed to have PCa ( P = .021). Of the patients with CI, 21% were found to have PCa on a separate core, whereas 38% of patients without CI were found to have PCa ( P = .0009). None of the other pathological features surveyed showed any significant association with PCa. High-grade PIN was a relatively common finding (14%) in this study and was positively associated with PCa on a separate core from the same accession biopsy. The negative association of CP with PCa within the same accession has not been reported previously and may be an artifact related to the clinical indications for a prostatic biopsy.

X-chromosome inactivation in the liver of female heterozygous OTC-deficient Sparse-furash mice

X-chromosome inactivation patterns were investigated in livers of nine spfash female heterozygous ornithine transcarbamylase (OTC)-deficient mice. Quantitative morphometric analysis of cellular mosaicism was performed on sections of frozen liver reacted with purified anti-OTC antibody and prepared for immunofluorescent microscopy. Analysis of enzymatic OTC activity was performed on sections of these livers using a radiochromatographic technique. Several areas of cellular mosaicism were seen in each of the histological sections that were studied. The distribution of the volume fraction of the liver tissue cells having cells with normal OTC content among the nine mice ranged from 20 to 70% and it correlated (r = 0.8, P = 0.005) with the enzymatic activities of the respective livers. The extreme variegation of mosaic patches in the liver suggests the high probability that a single needle biopsy will be diagnostic in females heterozygous for an OTC mutation. This study also suggests that at the time of X inactivation, the number of primordial liver embryonic cells is small and the observed variegation of liver mosaicism probably results from complex migration patterns of liver cells during fetal development. This study shows that the spfash mouse is a suitable animal model for quantitative studies of X-chromosome inactivation in liver using immunohistochemical staining of OTC protein.

Voluntary strength and muscle characteristics in untrained men and women and male bodybuilders

Eight untrained women (F), 13 untrained men (M), and 11 male bodybuilders (BB) did maximal elbow flexions on an isokinetic dynamometer at velocities of 30, 120, 180, 240, and 300 degrees/s, from which impact torque (IT), peak torque (PT), and work (W) were measured. Biceps and total flexor cross-sectional area (CSA) were measured by computerized tomographic scanning. Muscle fiber area, fiber composition, and collagen volume density were determined from single needle biopsies of biceps brachii. Biceps fiber number was estimated as the ratio of biceps CSA (corrected for connective tissue) to mean fiber area. PT and W decreased at higher velocities in M and BB but not in F; consequently, the correlation between CSA and PT and W was lower at 300 degrees/s (r = 0.58, 0.60) than 30 degrees/s (r = 0.80, 0.79). The ratio of PT to flexor CSA was similar in all groups at 30 degrees/s, whereas F had greater ratios than M and BB at the remaining velocities. F had greater W/CSA ratios than M and BB at all velocities. IT increased at higher velocities in all groups; the increase was greater in F and M than in BB. In contrast to PT and W, the correlation between IT and CSA was greater at 300 degrees/s (r = 0.67) than 30 degrees/s (r = 0.58), and there were no differences among groups in the IT/CSA ratios. Flexor CSA correlated negatively with the ratio of IT, PT, and W to CSA. Muscle fiber composition failed to correlate with any measure of strength. M and BB had greater biceps area, fiber number, and fiber area than F.(ABSTRACT TRUNCATED AT 250 WORDS)

Repeatability of fibre type and enzyme activity measurements in human skeletal muscle.

In order to assess the variability in repeated determination of human muscle fibre type distribution, fibre area and enzyme activity measurements, two biopsies were taken within 10 days in the same vastus lateralis for 12 females and 13 males, and in the right and in the left muscles for 25 other subjects (13 females and 12 males). Within muscle, intraclass reliability coefficients were 0.88, 0.82 and 0.56 for type I, IIa and IIb per cent fibres, respectively, and ranged from 0.74 to 0.82 for fibre areas and from 0.71 to 0.90 for enzyme markers of different metabolic pathways. Correlations between right and left muscle measurements were also high for fibre areas (from 0.85 to 0.91) and enzyme activities (from 0.71 to 0.87), except for phosphofructokinase (r = 0.63). In contrast, the right and left thigh muscle correlation reached 0.67, 0.40 and 0.64 for type I, IIa and IIb fibre distribution, respectively. Thus, the variation in muscle sampling and technical procedures reached about 15% of the total variation (i.e. total differences between subjects) for the proportion of fibre type I and IIa and about 20-25% for fibre areas and enzyme activities. On the other hand, the technical error for the proportion of fibre type I and IIa is about 6-7%. This implies that differences brought about by any experimental treatment on these skeletal muscle characteristics in human studies have to be of a relatively large magnitude before being detectable. On the other hand, fibre areas and enzyme activities measured in single needle biopsy sample, from one of the vastus lateralis muscles, are quite representative of the other vastus lateralis. Similarity in fibre type proportion between right and left vastus lateralis cannot be postulated, however, without investigating both muscles.

Renal biopsy in the normal cat: an examination of the effects of a single needle biopsy

Eleven healthy cats were subjected to a single, percutaneous renal biopsy with a disposable biopsy needle and thereafter monitored clinically and by means of laboratory analyses of blood and urine until euthanasia at intervals up to two months after biopsy. Biopsy specimens were obtained at each attempt and the specimen length and numbers of glomeruli compared favourably with results from normal dogs biopsied with Franklin-Silverman needles. At necropsy radiographic studies demonstrated renal vascular changes and histological examinations of the biopsied kidneys revealed lesions varying from barely discernible linear scars to extensive haemorrhage and wedge-shaped infarcts. A direct relationship was established between the severe renal lesions in seven cats and biopsy specimens containing medullary tissue and major renal blood vessels.

Observer error and sampling variability tested in evaluation of hepatitis and cirrhosis by liver biopsy.

In 50 patients with chronic active liver disease, observer and sampling error in histologically evaluating hepatitis and cirrhosis after blind-needle biopsy of the liver was assessed from coded tissue. This was done by repeated readings of the same specimens by the same pathologist, by sequential biopsies from the same patients with cirrhosis, and by multiple simultaneous biopsies from adjacent areas of the liver. Observer error was small. The consistency of grading the individual histologic characteristics of hepatitis was 90%, and the reproducibility of the degree of either hepatitis or cirrhosis was 94%. Sampling error was also trivial in hepatitis, indicating that a single needle biopsy accurately reflects the type and degree of inflammation and necrosis in adjacent areas of the liver. By contrast, sampling error was of considerable magnitude when the presence of cirrhosis in patients known to have the lesion was sought, since confirmation by simultaneous or sequential biopsies was made in only 33% of the cases.