MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

Evaluation of neuroendocrine markers in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>The purpose of the study was to examine serotonin, CD56, neurone-specific enolase (NSE), chromogranin A and synaptophysin by immunohistochemistry in renal cell carcinomas (RCCs) with special emphasis on patient outcome.</p> <p>Methods</p> <p>We studied 152 patients with primary RCCs who underwent surgery for the removal of kidney tumours between 1990 and 1999. The mean follow-up was 90 months. The expression of neuroendocrine (NE) markers was determined by immunohistochemical staining using commercially available monoclonal antibodies. Results were correlated with patient age, clinical stage, Fuhrman grade and patient outcome.</p> <p>Results</p> <p>Eight percent of tumours were positive for serotonin, 18% for CD56 and 48% for NSE. Chromogranin A immunostaining was negative and only 1% of the tumours were synaptophysin immunopositive. The NSE immunopositivity was more common in clear cell RCCs than in other subtypes (<it>p </it>= 0.01). The other NE markers did not show any association with the histological subtype. Tumours with an immunopositivity for serotonin had a longer RCC-specific survival and tumours with an immunopositivity for CD56 and NSE had a shorter RCC-specific survival but the difference was not significant. There was no relationship between stage or Fuhrman grade and immunoreactivity for serotonin, CD56 and NSE.</p> <p>Conclusions</p> <p>Serotonin, CD56 and NSE but not synaptophysin and chromogranin A are expressed in RCCs. However, the prognostic potential of these markers remains obscure.</p

HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

Correction: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 96 Issue: 5 Pages: 852-852 DOI: 10.1016/j.ajhg.2015.04.001 Published:MAY 7 2015Peer reviewe

Differential gene expression in prostate cancer:identification of genes expressed in prostate cancer, androgen-dependent and androgen-independent LNCaP cell lines, and characterization of TMPRSS2 expression

Abstract Prostate cancer is the most common solid tumor among men in Western industrialized countries. A major problem in prostate cancer treatment is the development of androgen-independence, as androgen-deprivation therapy is the basic therapy for the disease. Molecular mechanisms behind prostate cancer and androgen-independent growth development are poorly known. In this study, subtractive hybridization was used for the generation of a cDNA library specific for prostate cancer. Analysis of the cDNA library revealed over-expression of several ribosomal proteins namely L4, L5, L7a, L23a, L30, L37, S14 and S18, in prostate cancer cell lines. Over-expression of L7a and L37 was also confirmed in prostate cancer tissue samples. Further, cDNA array was used in order to examine differentially expressed genes in androgen-dependent and androgen-independent prostate cancer cell line LNCaP. Monoamine oxidase A, an Expressed Sequence Tag (EST) similar to rat P044, and EST AA412049 were highly over-expressed in androgen-dependent LNCaP cells. Tissue-type plasminogen activator, interferon-inducible protein p78 (MxB), an EST similar to galectin-1, follistatin, fatty acid-binding protein 5, EST AA609749, annexin I, the interferon-inducible gene 1-8U and phospholipase D1 were highly over-expressed in androgen-independent LNCaP cells. The EST similar to rat P044, the EST similar to galectin-1, follistatin, annexin I and the interferon-inducible gene 1-8U were also expressed in benign prostatic hyperplasia tissue. The Y-linked ribosomal protein S4, Mat-8, and EST AA307912 were highly expressed in benign prostatic hyperplasia tissue. In situ hybridization of mouse embryos and adult mouse tissues revealed the expression of TMPRSS2 in the epithelium throughout the gastrointestinal, urogenital and respiratory tracts during development. In human multiple tissue RNA dot blot, the highest level of expression was detected in prostate, and lower levels in colon, stomach and salivary gland. TMPRSS2 transcript levels were significantly higher in prostate cancer tissue between benign and malignant epithelium of prostate cancer patients with untreated disease. Similarly, in poorly differentiated adenocarcinomas, expression in malignant tissue was significantly higher. Enzymatic mutation detection and direct sequencing of TMPRSS2 coding region revealed only one deletion in aggressive disease among 9 non-aggressive and 9 aggressive prostate cancer samples. No other mutations were found. Detected 7-base pair deletion leads to premature stop codon and disruption of serine protease substrate binding and catalytic active site. We cloned several potential genes whose expression is changed during prostate cancer initiation or progression. These genes may serve as prostate cancer markers, and further studies are needed to clarify the expression of these proteins during the disease

Eturauhassyövän kehittyvä diagnostiikka

Tiivistelmä Eturauhassyöpäepäily perustuu yleensä oireettomalta tai virtsaoireiselta mieheltä otetun verinäytteen ­PSA-arvon poikkeavuuteen. Diagnoosi perustuu valtaosin eturauhasen paksuneulabiopsian histologiaan. Hoito suunnitellaan syövän riskiluokituksen mukaan potilaan perussairaudet ja odotettavissa oleva ­elinikä huomioiden. Tuseerauslöydöksen ja PSA-tason lisäksi monimuuttujainen magneettikuvaus kohdennettuine neula­näytteineen, kehittyvät biomarkkerit ja riskilaskurit ovat hyödyllisiä diagnostiikassa ja riskin arvioinnissa.Summary Prostate cancer is the most frequently diagnosed cancer in Finland and the second most common cause of cancer death among Finnish males. An abnormal PSA blood test from an asymptomatic man or a man seeking help for urinary symptoms is the usual reason for further diagnostic tests. A diagnosis based on symptoms of metastatic cancer is less frequent. The diagnosis is mainly based on histological analysis of transrectal needle biopsies. To avoid diagnosis of clinically insignificant cancers among men with slightly abnormal PSA values (< 10 µg/l), further risk stratification with other biomarkers, risk calculators or multiparametric magnetic resonance imaging (MRI) is suggested before biopsy. Most clinically significant cancers are identified with MRI, with the option to perform targeted biopsies of abnormal lesions. This improves the risk classification of cancer. With the PSA test both clinically insignificant and aggressive cancers are diagnosed. The treatment decisions are based on the risk classification of the cancer. Low risk cancers are suggested to be treated primarily by active surveillance

Transition to targeted therapies improved the prognosis and increased the utilization of medical treatments among patients with synchronous metastatic renal cell cancer

Abstract Since the introduction of targeted therapies (TTs) for metastatic renal cell cancer (mRCC) in 2005, a limited amount of epidemiological data on efficacy of modern drug therapies for synchronous mRCC has been published. We present a comprehensive nationwide cohort including all cases of primarily metastasized renal cell cancer among adults diagnosed between 2005 and 2010, based on data from the Finnish Cancer Registry and patient records from treating hospitals. Applied treatment protocols and survival outcomes were analyzed. A total of 977 patients were included in the analysis; 499 patients were diagnosed between 2005 and 2007 and 478 patients were diagnosed between 2008 and 2010. The median overall survival (OS) was 8.80 months (95% confidence interval (CI): 7.60–10.02). The median OS of the patients diagnosed at the latter era was significantly better (11.1; 95% CI: 8.8–13.4 vs. 7.0; 95% CI: 5.7–8.3 months, p ≤ 0.001). A total number of 524 (53.8%) patients received drug therapy. Altogether, TTs including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTORi), and vascular endothelial growth factor inhibitor covered 331 (63.2%) of first-line treatments, whereas interferon and its combinations with chemotherapy were used for 186 (35.5%) patients. The median OS rates for TT and interferon as first-line therapy groups were 19.9 (16.9–22.8) and 14.9 (12.3–17.4) months, respectively. The OS for patients who did not receive drug therapy after cytoreductive nephrectomy was dismal. We found that the OS estimate of mRCC patients in Finland has improved since the introduction of tyrosine kinase inhibitors. However, the prognosis remains poor for frail, elderly patients with an impaired performance status

Nephrectomy improves the survival of metastatic renal cell cancer patients with moderate to good performance status:results from a Finnish nation-wide population-based study from 2005 to 2010

Abstract Background: The purpose of this study was to evaluate the effects of cytoreductive nephrectomy (CN) and metastasectomies on the survival of patients with synchronous metastatic renal cell cancer (mRCC) using real-life, population-based national dataset. Methods: Nationwide data, including all cases of synchronous mRCC in Finland diagnosed on a 6-year timeframe, based on the Finnish Cancer Registry and complemented with patient records from the treating hospitals, were analyzed. Patients with Eastern Cooperative Oncology Group (ECOG) performance status 3–4 were excluded. Univariate and adjusted multivariable survival analysis were performed, including subgroup analysis for patients with different medical therapies. Nephrectomy complications were also analyzed. Results: A total of 732 patients were included in the analysis. CN was performed for 389 (53.1%) patients, whereas 68 (9.3%) patients underwent nephrectomy and metastasectomies of all lesions (surgery with curative intent). Median overall survival (OS) for patients who did not undergo nephrectomy was 5.9 (95% confidence interval [CI] = 4.6–7.2) months. Patients who had a CN had a median OS of 16.6 (95% CI = 14.2–19.1, p &lt; 0.001) months, whereas patients who had surgery with curative intent had a median OS of 51.3 (95% CI = 36.0–66.6, p &lt; 0.001) months. The survival benefit of CN and metastasectomies remained significant in all medical therapy subgroups and in both of the applied multivariable statistical models. Conclusions: Surgical treatment of metastatic renal cell cancer is associated with a significant survival benefit in patients with good and moderate performance status, regardless of the chosen medical therapy

Paikallisen eturauhassyövän radikaalitavoitteisen hoidon vaikutus potilaiden elämänlaatuun

Abstract JOHDANTO. Eturauhassyövän hoidot voivat vaikuttaa elämänlaatuun. Tutkimuksen tavoitteena oli selvittää eturauhassyöpäpotilaiden elämänlaatua hoidon eri vaiheissa. POTILAAT JA MENETELMÄT. Potilaat täyttivät syöpäpotilaan QLQ-C30-elämänlaatukyselyn sekä eturauhassyöpäpotilaiden elämänlaadun arviointiin kehitetyt QLQ-PR25- ja EPIC-26-kyselyt ennen radikaalihoitoa, noin kuukausi hoidon jälkeen sekä 6, 12, 24 ja 36 kuukautta hoidon jälkeen. Hoitojen välisiä elämänlaatueroja ajan suhteen arvioitiin lineaarisen sekamallin avulla. TULOKSET. Hoitoa edeltävään kyselyyn vastasi 101 leikattua, 125 ulkoisella sädehoidolla hoidettua ja 21 kudoksensisäisellä sädehoidolla hoidettua miestä. Ulkoisella sädehoidolla hoidettujen yleinen elämänlaatu oli heikompi jo ennen hoitoa. Leikkaushoito aiheutti virtsankarkailua ja erektiokyvyn menetystä, jotka eivät aina korjaantuneet. Sädehoidetuilla oli enemmän suolioireita. PÄÄTELMÄT. Eturauhassyövän radikaalihoito aiheuttaa merkittäviä elämänlaatuun vaikuttavia, usein pitkäkestoisia haittavaikutuksia. Tuloksia voidaan hyödyntää potilasinformaatiossa suunniteltaessa eturauhassyövän radikaalihoitoja