Renal tumor biopsies are associated with a low complication rate.

BACKGROUND: Due to the high incidence of benign lesions in renal masses, numerous studies have been performed to clarify the value of core needle biopsies. The aim of the present study was to describe the complication rate after renal tumor biopsies (RTB), in order to make recommendations on observation after the procedure. MATERIALS AND METHODS: Data from all patients who underwent percutaneous ultrasound-guided RTB between February 2013 and October 2016 due to CT verified solid renal masses were prospectively collected and kept in a well-maintained database. Complications were collected retrospectively and classified according to the Clavien-Dindo (CD) classification system. RESULTS: Data from 224 consecutive patients were retrieved. Thirteen patients underwent unilateral repeat biopsies and three patients underwent bilateral biopsies; thus, a total of 240 procedures were analyzed. A total of 124 patients (51.7%) were discharged within 4 hours after the RTB procedures and 110 patients (45.8%) were discharged within 24 hours. The remaining six patients (2.5%) were hospitalized for more than 1 day, all due to co-morbidities which were unrelated to the procedure. In total, five patients (2.1%) experienced post-biopsy complications: one case of iatrogenic pneumothorax, one case of spontaneously resolving hematuria and three cases of fever. All complications were CD ≤2 and all patients with complications were discharged within 24 hours, except for one patient who was hospitalized for 3 days due to management of bone pain. No correlation was found between the number of biopsies and complication rate. CONCLUSION: The overall complication rate following ultrasound-guided biopsies of renal tumors was low and all complications were mild. Given the current evidence, it is believed that ultrasound-guided RTB can be done as an outpatient procedure without the need for hospitalization.

Core needle biopsy clarify the histology of the small renal masses and may prevent overtreatment.

PURPOSE: The purpose of the study was to evaluate the diagnostic accuracy of core biopsy in small renal masses ≤ 4 cm in response to the rising prevalence of renal masses. METHODS: Data from 129 consecutive patients who underwent biopsies of solid renal masses of ≤ 4 cm were prospectively collected between September 2014 and January 2017. In cases with inconclusive biopsies, a repeat biopsy was recommended. Histology from surgical specimens was used as gold standard to evaluate the accuracy of renal biopsies. RESULTS: The initial biopsies revealed malignancy in 77 patients (59.7%) and benign histology in 35 patients (27.1%), whereas 17 (13.2%) were inconclusive. Fifty-six patients with malignant histology underwent either partial or radical nephrectomy according to the physicians' recommendation, while two patients with benign histology requested surgery. In all cases, the biopsy diagnosis was confirmed upon final histopathology. Of the inconclusive cases, six underwent repeat biopsies all with benign histology. Further, three patients opted for immediate partial nephrectomy with benign oncocytoma in two and renal cell carcinoma in the third. The remaining eight patients opted for follow-up CT scans with no sign of progression with a minimum of 6-month follow-up. No biopsy related complications were reported in the first 30 days after RTB. Overall, the treatment strategy changed in 45 of 129 (35%) patients due to biopsy results. This was either due to benign findings or due to the discovery of non-renal cell cancers. CONCLUSION: Core needle biopsies of solid renal masses ≤ 4 cm have excellent accuracy and may be used to select the correct treatment. Importantly, they may serve to prevent overtreatment of benign tumors.

Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study.

BACKGROUND: The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting. PATIENTS AND METHODS: Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method. RESULTS: Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml. CONCLUSION: We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values. CLINICAL TRIAL NUMBER: NCT00672282.

Microsatellite instability is infrequent in medullary breast cancer.

Microsatellite instability (MSI), characterized by contraction or expansion in microsatellite length or short tandem repeats compared with germline lengths, is found in 85% to 90% of colon cancer arising in hereditary nonpolyposis colorectal cancer families. These cancers commonly have characteristic histologic appearances, including medullary features with intense lymphoid infiltrates. In pancreatic cancer, a rare medullary histologic subtype more often demonstrates MSI than the more common adenocarcinoma subtype. We hypothesized that the medullary histologic pattern might correlate with MSI in additional tumor types and analyzed 8 cases of typical and atypical medullary carcinoma of the breast. Tumor and normal DNA was extracted from paraffinized tissue blocks of tumor and histologically uninvolved axillary lymph nodes, respectively. We analyzed the tumors for instability in 5 primary (BAT25, BAT26, D17S250, D5S346, D2S123) and 3 alternative (BAT40, D18S55, D18S58) microsatellites recommended at the National Cancer Institute--sponsored conference for diagnosis of MSI in colorectal cancer. All 8 tumors were microsatellite stable at the 8 loci, suggesting that MSI is not commonly associated with medullary or atypical medullary breast carcinoma, in contrast with the reported association with medullary tumors of the colon and pancreas.

Detection of microsatellite instability.

In 1993, three groups independently discovered that the lengths of microsatellites in tumors could vary from the normally constant pattern defined at birth (5-5) (see review in ref. 4). This discovery has been designated either microsatellite instability (MSI) or replication errors (RER). A recent international consensus conference convened by the National Cancer Institute defined MSI/RER as "a change in length due to either insertion or deletion of repeating units, in a microsatellite within a tumor when compared to normal tissue" (5). Microsatellites are regions of repetitive DNA in which the repeating unit is small, varying in length from 1 to 6 nucleotides, and in which the number of repeating units in a microsatellite can vary from 10-60 (6-7). Because microsatellite lengths generally vary from person to person, they have received widespread use in forensics, gene mapping, parentage testing.

Detection of microsatellite instability by fluorescence multiplex polymerase chain reaction.

We have created a clinical molecular diagnostic assay to test for microsatellite instability (MSI) at multiple loci simultaneously in paraffin-embedded surgical pathology colon resection specimens. This fluorescent multiplex polymerase chain reaction (PCR) assay analyzes the five primary microsatellite loci recommended at the 1997 National Cancer Institute-sponsored conference on MSI for the identification of MSI or replication errors in colorectal cancer: Bat-25, Bat-26, D2S123, D5S346, and D17S250. Amplicon detection is accomplished by capillary electrophoresis using the ABI 310 Genetic Analyzer. Assay validation compared 18 specimens previously assessed by radioactive PCR and polyacrylamide gel electrophoresis detection to results generated by the reported assay. Germline and tumor DNA samples were amplified in separate multiplex PCR reactions, sized in separate capillary electrophoresis runs, and compared directly to identify novel length alleles in tumor tissue. A concordance of 100% between the two modalities was achieved. The multiplex assay routinely detected a subpopulation of 10% tumor alleles in the presence of 90% normal alleles. A novel statistical model was generated that corroborates the validity of using results generated by analysis of five independent microsatellites to achieve a single overall MSI diagnosis. The assay presented is superior to standard radioactive monoplex PCR, polyacrylamide gel electrophoretic analysis, primarily due to the multiplex PCR format.

Pseudo-spikes are common in histologically benign lymphoid tissues.

T cell receptor gene rearrangement is a classic marker of T cell clonality and is a useful adjunct in the diagnosis of T cell lymphomas and leukemias. Rearranged V-J gene segments amplified by polymerase chain reaction (PCR) are traditionally analyzed by polyacrylamide gel electrophoresis. We and others have analyzed TCR-gamma PCR products using capillary gel electrophoresis, which produces single nucleotide resolution and provides improved diagnostic sensitivity over conventional methods. However, with this marked increase in resolution and sensitivity, it is necessary to re-define normal variation of TCR-gamma gene rearrangement in control tissues to allow appropriate interpretation of monoclonality if present. Using DNA capillary gel electrophoresis, we examined the spectrum of normal patterns for TCR-gamma in a variety of T-cell-rich, histologically benign tissue types, including spleen, lymph node, tonsil, and blood, and compared this with the patterns in T cell lymphoma samples. We defined relative peak heights as h1/h2, where h1 represents the peak height of the largest peak above the normally distributed population, and h2 represents the peak height of the normally distributed curve. We found spikes in almost 20% of histologically benign samples with relative peak heights that were more than 0.5 and up to 1.5. We designated these as pseudo-spikes, because they may be mistaken for monoclonal spikes. In contrast, the relative peak height of the T cell lymphoma samples that showed clonal rearrangement was much higher than that of the pseudo-spikes, being at least 2 in 11/11 and at least 3 in 10/11 cases. Our data suggest that peaks with relative height of at least 3 represent a true clonal population in diagnostic samples. Peaks with relative heights of less than 1.5 may be insignificant, while peaks with relative heights between 1.5 to 3 may warrant further evaluation. Although capillary gel electrophoresis is superior in assessing T cell clonality, caution must be exercised when interpreting results, because pseudo-spikes appear to be common in benign tissues with lymphoid populations and are not necessarily indicative of clonal malignant T cell population.