Récidive testiculaire isolée d’un adénocarcinome prostatique révélée par TEP/TDM 18F-fluorocholine

With the development of new PET tracers, nuclear medicine has become a central element in the search for prostate cancer recurrence. A 75-year-old patient followed for a prostate adenocarcinoma was referred to our center for biological recurrence, with a gradual rise of prostatic specific antigen (PSA). A pelvic MRI and ¹⁸F-fluorocholine PET/CT were performed, both showing no strong evidence of local recurrence. This last examination however revealed an intense pathological radiotracer uptake only in the left testicle. After performing a complementary ultrasound imaging, orchiectomy revealed a metastatic testicular localization of the prostatic adenocarcinoma. PSA control after surgery had normalized. This case emphasizes one of the unusual presentations of metastatic prostatic disease to be aware of.     

Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia

Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients’ sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.     

Prostate-specific antigen levels among cirrhotic patients

PURPOSE: The aim of this study was to determine serum prostate-specific antigen (PSA) levels in patients with liver cirrhosis. PATIENTS AND METHODS: Between January 1995 and August 2001, 216 men with cirrhosis were evaluated. The extent of their liver disease was classified according to the Child-Pugh classification. Serum PSA levels were measured with the Hybritech Tandem-R RIA method and matched with age-related reference PSA levels. Digital rectal examination (DRE) was performed in all patients. Patients with elevated PSA levels and/or abnormal DRE were recommended to undergo further assessment including transrectal ultrasonography (TRUS) and biopsy performed by an urologist. RESULTS: Two hundred and sixteen men (mean age 54.09 +/- 9.09 years, range 25-76) with cirrhosis were examined. Their mean PSA value was 0.57 +/- 0.84 ng/mL and tended to be lower than in the normal population. The degree of PSA decrease was found to parallel the severity of the liver disease (p=0.002). The mean serum PSA level increased with each age decade in a statistically significant manner (p<0.001). Four patients (three with elevated PSA values) underwent prostate biopsy. Three biopsies were positive for prostate cancer, the other showed evidence of benign prostatic hyperplasia (BPH). CONCLUSION: Serum PSA is influenced by the severity of liver disease and its levels tend to be lower in cirrhotic patients than in the normal population. However, serum PSA can still be considered a reliable marker in the clinical management of prostatic disease in patients with cirrhosis.     

Metastatic prostate cancer complicated with chronic disseminated intravascular coagulopathy causing acute renal failure, mimicking thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: pathomechanism, differential diagnosis and therapy related to a case

Disseminated intravascular coagulopathy (DIC) is characterized as activation of the clotting system resulting in fibrin thrombi, gradually diminishing levels of clotting factors with increased risk of bleeding. Basically two types of DIC are distinguished: (1) chronic (compensated) - with alteration of laboratory values and (2) acute (non-compensated) - with severe clinical manifestations: bleeding, shock, acute renal failure (ARF), transient focal neurologic deficit, delirium or coma. Chronic DIC related to metastatic neoplasia is caused by pancreatic, gastric or prostatic carcinoma in most of the cases. Incidence rate of DIC is 13-30% in prostate cancer, among those only 0.4-1.65% of patients had clinical signs and symptoms of DIC. In other words, chronic DIC is developed in one of eight patients with prostate cancer. DIC is considered as a poor prognostic factor in prostatic carcinoma. The similar clinical and laboratory findings of TTP-HUS (thrombotic thrombocytopenic purpura - hemolytic uremic syndrome) and DIC makes it difficult to differentiate between them. A 71 years old male patient with known chronic obstructive pulmonary disease, benign prostatic hyperplasia, significant carotid artery stenosis, gastric ulcer and alcoholic liver disease was admitted to another hospital with melena. Gastroscopy revealed intact gastric mucosa and actually non-bleeding duodenal ulcer covered by clots. Laboratory results showed hyperkalemia, elevated kidney function tests, indirect hyperbilirubinemia, increased liver function tests, leukocytosis, anemia, thrombocytopenia and elevated international normalized ratio (INR). He was treated with saline infusions, four units of red blood cells and one unit of fresh frozen plasma transfusions. Four days later he was transported to our Institution with ARF. Physical examination revealed dyspnoe, petechiae, hemoptoe, oliguria, chest-wall pain and aggressive behavior. Thrombocytopenia, signs of MAHA (fragmentocytes and helmet cells in the peripheral blood), normal INR, elevated lactate dehydrogenase (LDH) and ARF suggested TTP-HUS. Hemodialysis and six plasmaferesis (PF) were carried out. After the fifth PF, skin manifestations of thrombotic microangiopathy occurred on the feet. Clotting analysis revealed elevated D-dimer (>5 μg/mL), normal fibrinogen (3.2 g/L), a slightly raised INR (1.36) and activated partial prothrombin time (APTT) (45.8 sec), normal reticulocyte (57 G/L) and a slightly low platelet count (123 G/L), which proved to be chronic DIC. Therapeutic dose of low-molecular-weight heparin (LMWH) was started. Elevated prostate-specific antigen (PSA) (109.6 ng/mL) suggested prostatic carcinoma. Prostate biopsy revealed adenocarcinoma (Gleason: 4+4 for left lobe and 3+3 for right lobe). Elevated alkaline phosphatase suggested metastases in the bone, which were confirmed by bone scintigraphy. Combined androgen blockade (CAB) was started. After three months follow-up our patient's status is satisfactory. PSA is in the normal range (4.6 ng/mL). Thrombocytopenia of uncertain origin with normal or raised INR, APTT, elevated D-dimer, normal fibrinogen and reticulocyte count prove the diagnosis of chronic DIC. This process warrants searching for metastatic neoplasia. Due to the relatively low serum levels of circulating procoagulant factors (e.g. tissue factor), therapeutic dose of LMWH can be used with good efficiency in chronic DIC with low risk of bleeding. Severe DIC as a complication of metastatic prostate cancer can be treated by androgen deprivation therapy (ADT) or CAB in combination with ketokonazole and concomitant use of supportive treatment. Deme D, Ragán M, Kovács L, Kalmár K, Varga E, Varga T, Rakonczai E. Metastatic prostate cancer complicated with chronic disseminated intravascular coagulopathy causing acute renal failure mimicking thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: pathomechanism, differential diagnosis and therapy related to a case.     

Cancer de la prostate : les marqueurs biologiques

Normal prostate cells and prostate cancer cells produce prostate-specific antigen (PSA): thus, it is frequently increased in non-malignant conditions such as prostatitis and benign prostatic hyperplasia. Indeed, PSA is an excellent biomarker to monitor disease progression. The low diagnostic specificity of PSA leads to many false-positive and a large number of biopsies. These well-recognized limitations of PSA suggest that new prostate cancer biomarkers could play a useful role in reducing the number of unnecessary biopsies.     

HPC2 variants and screen-detected prostate cancer

Two studies have reported significant associations between susceptibility to prostate cancer and two common missense variants of the HPC2/ELAC2 gene, with estimated relative risks in the range of two- to threefold. We investigated whether these polymorphisms could be informative in the prediction of the presence of prostate cancer in men undergoing prostatic biopsy for the evaluation of an elevated serum-PSA level (> or = 4.0 ng/ml). We genotyped 944 men who underwent a prostate biopsy at our institution, as well as a control population of 922 healthy, unselected women from the same population. The prevalence of the HPC2 Ala541Thr allele was similar in men with prostate cancer (6.3%), men with other prostatic conditions (6.8%), and healthy women (6.3%) (P = .83). We conclude that HPC2 genotyping is unlikely to be a useful adjunct to PSA in the prediction of the presence of biopsy-detected prostate cancer in asymptomatic men.     

Benign prostatic hyperplasia: does prostate size matter?

Recent studies and analyses have confirmed that baseline prostate volume is related to progression of benign prostatic hyperplasia (BPH) as well as to negative outcomes related to BPH, such as acute urinary retention (AUR) and need for surgery, and can also predict response to therapy. Other investigations have determined that prostate-specific antigen (PSA) level has good predictive value for assessing prostate volume. Strong evidence exists that baseline serum PSA level, like baseline prostate volume, predicts future prostate growth. Randomized placebo-controlled finasteride trials have shown that men with larger prostate volumes and higher PSA levels experience a clinically significant response to therapy compared with those with smaller prostate volumes and lower PSA levels. It has also been demonstrated that men with larger prostate glands and higher PSA levels are at increased risk for AUR and BPH-related surgery but that finasteride reduces these risks. Moreover, doxazosin and finasteride, alone and in combination, have been shown to significantly reduce BPH clinical progression.     

Serum prostate-specific antigen determination in prostatic carcinoma

Prostate-specific antigen (PSA) is a tissue-specific glycoprotein identified by Wang in 1979. It is synthesized in the prostate independently of prostatic acid phosphatase (PAP). A total of 199 subjects were divided into four groups: controls aged less than 50 years, controls aged more than 50 years, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. PSA cut-off value was set at 10 ng/ml (mean for the BPH group plus 2 SD). With this cut-off value PSA could not be used as an early predictor of prostatic carcinoma. The association of PSA and PAP in prostatic cancer increases the number of patients with positive biological markers.     

Expression and purification of recombinant active prostate-specific antigen from Escherichia coli

Human prostate-specific antigen (PSA), a 33 kDa serine protease with comprehensive homology to glandular kallikrein, is secreted from prostatic tissue into the seminal fluid and enters into the circulation. The level of PSA increases in the serum of patients with prostatic cancer and hence is widely employed as a marker of the disease status. In particular, an enzymatically active PSA that is a form cleaved at the N-terminal seven-amino-acids prosequence, APLILSR, of proPSA may play an important roll in the progression of prostate cancer. Thus, the presence of the active form would selectively discriminate the cancer from benign prostatic hyperplasia. In this study, we developed a convenient purification method for the acquisition of active PSA and proPSA. Recombinant proPSA and active PSA were expressed directly in Escherichia coli, easily and efficiently isolated from inclusion bodies, refolded, and purified. Moreover, the enzymatic activity of the recombinant active PSA was confirmed as serine protease using chromogenic chymotrypsin substrate. This purified active PSA could be further applied to scrutinize the biological or conformational characteristics of the protein and to develop specific diagnostic and/or therapeutic agents against prostate cancer.     

血清PSA、EGF在不同类型良性前列腺增生患者中表达意义及其与术后疾病转归的相关性分析

摘要 目的：分析血清前列腺特异抗原（PSA)、表皮生长因子（EGF)在不同类型良性前列腺增生患者中低表达意义及其与术后疾病转归的相关性。方法：选择自2020年1月至2022年12月在我院接受手术治疗的128例良性前列腺增生患者作为研究对象,根据术后病理活检结果进行分组,间质结节组（16例）、腺肌性结节组（32例）、纤维腺瘤性结节组（12例）、腺性结节组（30例）和混合结节组（38例）,其中以间质增生为主60例、以腺体增生为主68例。检测所有患者血清PSA、EGF的表达水平,以术后6个月的国际前列腺症状评分（IPSS评分）<8分判定为预后良好,分析血清PSA、EGF在预后良好组与预后不良组之间的差异性及与IPSS评分的关系。结果：血清PSA、EGF表达水平在间质结节组、腺肌性结节组、纤维腺瘤性结节组、腺性结节组和混合结节组间比较有差异（P<0.05）;以腺体增生为主的良性前列腺增生患者血清PSA、EGF表达水平均明显高于以间质增生为主的患者（P<0.05）;经ROC曲线分析,血清PSA联合EGF预测以腺体增生为主的良性前列腺增生的敏感度为86.42%,特异度为65.34%,AUC为0.930;所有患者均获得随访6个月,预后良好98例、预后不良30例;预后不良组血清PSA、EGF表达水平均明显高于预后良好组（P<0.05）;经Pearson相关性分析,良性前列腺增生患者血清PSA、EGF表达水平均与IPSS评分呈负相关（r值分别为-0.348、-0.417,P值均为0.000）。结论：血清PSA、EGF在不同病理类型良性前列腺增生患者中表达差异显著,以间质增生为主的患者,以腺体增生为主的患者血清PSA、EGF表达水平更高,两者均与术后疾病转归密切相关,值得临床予以重视。     

Prostate carcinoma metastatic to the skin as an extrammamary Paget¿s disease

ABSTRACT: AimThe current paper describes a case of prostatic adenocarcinoma metastatic to the skin presenting as an extrammamary Paget's disease, a very rare and poorly characterised morphological entity. We report a case of prostatic carcinoma metastatic to skin showing a pattern of extramammary Paget's disease which has not been clearly illustrated in the literature Case presentation: A 63 year-old man with prostatic adenocarcinoma developed cutaneous metastases after 16 years. The inguinal metastases were sessile and 'keratotic.' The tumour displayed solid, glandular areas as well as a polypoid region suggestive of extramammary Paget's disease were identified.Discussion and conclusionsWe review the diagnostic criteria that have led to the correct histopathological diagnosis in this case. A differential diagnosis of the pagetoid spread in the skin and various forms of cutaneous metastases determined by a prostatic adenocarcinoma as well as the role of immunohistochemistry in establishing the prostatic origin are presented in the context of this case. Although, morphologically the cells presented in the skin deposits were not characteristic for adenocarcinoma of prostate, immunohistochemistry for PSA and PSAP suggested a prostatic origin.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1395450057455276.     

血清前列腺特异性抗原与前列腺增生的相关性研究

目的:探讨前列腺增生患者年龄,前列腺体积以及BMI与血清前列腺特异性抗原(PSA)之间的关系。方法:对224例前列腺增生患者的年龄,前列腺体积以BMI与PSA的相关性进行Spearman相关性分析。结果:224例前列腺增生患者有25%的患者PSA水平高于正常,并且年龄,前列腺体积与血清PSA存在明显的正相关:(r=0.672.P<0.01,r=0.785.P<0.01),而血清PSA与BMI指数存在明显的负相关:(r=-0.873,P<0.01)。结论:前列腺增生患者的血清PSA值随患者年龄增长和体积增大而增加,对于PSA轻度升高的前列腺增生患者,要考率到体重因素对结果的影响。     

Biomarkers for prostate cancer

The detection of prostate cancer using a blood test has by many standards changed the face of the disease. Despite this tremendous success, there are limitations attributed to the use of prostate specific antigen (PSA) as a means to screen and detect prostate cancer. PSA, as its name implies, is not specific for prostate cancer and as such is often found elevated in other prostatic diseases/symptoms associated with the aging male. Clearly, more specific marker(s) that could identify which individuals actually have prostate cancer and differentiate them from those without the disease would be of tremendous value. The search for more accurate and clinically useful biomarkers of prostate cancer has been extensive. This has focused on individual markers, as well as groups of markers. Included among these are PSA isoforms, pathological indicators and stains, nucleic acids and others. This article highlights the discovery of PSA as a first blood‐based biomarker for prostate cancer detection, as well as other molecular biomarkers and their potential application in detection of the disease. J. Cell. Biochem. 108: 3–9, 2009. © 2009 Wiley‐Liss, Inc.     

The contribution of prostatic acid phosphatase and prostatic specific antigen in the diagnosis of prostatic cancer

Prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) were measured by immunochemical methods using test preparations from two different companies. In 66 patients with benign hyperplasia of the prostate a good correlation was found only between PSA levels (orthogonal regression analysis: y = 1.77 x -0.68; r = 0.995). Discrimination analysis between benign hyperplasia and new prostatic cancer (28 patients), using ROC curves, revealed a sensitivity for prostatic cancer of about 30 percent using both PAP methods and of about 58 percent using both PSA methods at the 95-percentile of benign hyperplasia. The PSA methods were both more sensitive in detecting prostatic cancer than the PAP methods.     

Hürthle cell Thyroid Carcinoma Presenting as A “Hot” Nodule

ObjectiveTo report an unusual clinical scenario and a rare histopathologic finding of Hürthle cell thyroid carcinoma in a patient with an autonomous thyroid nodule.MethodsWe describe the presentation and clinical course leading to the surprising histopathologic diagnosis of Hürthle cell carcinoma in a pediatric patient who was diagnosed with hyperthyroidism presenting as a solitary toxic nodule.ResultsA 13-year-old white girl presented with a recent history of a palpable thyroid nodule during a routine primary care clinic visit. She was asymptomatic, and thyroid function tests revealed a suppressed thyrotropin concentration, high-normal free thyroxine concentration, and elevated triiodothyronine concentration. The patient underwent dedicated thyroid ultrasonography revealing a 3.5-cm complex mass in the left lobe with increased central vascularity. Iodine 123 imaging of the thyroid demonstrated homogenous, hyperintense activity in the left lobe. The right lobe was not visualized. A solitary toxic nodule was diagnosed, and, considering her age, she was referred for surgical management. The patient underwent a left lobectomy with isthmusectomy. Pathologic examination revealed a 5-cm, encapsulated, well-differentiated Hürthle cell carcinoma with negative margins and no lymphovascular invasion. The patient underwent subsequent completion thyroidectomy with no evidence of residual carcinoma in the right thyroid lobe.ConclusionsMalignancy in autonomously functioning thyroid nodules is rare. Most of the thyroid nodules presenting as “hot” on radioiodine scintigraphy are benign follicular adenomas. However, this case represents a rare clinical entity, and it highlights the need for clinicians to be vigilant and aware that occasionally carcinomas can masquerade as scintigraphic “hot” nodules. (Endocr Pract. 2011;17:e68-e72)     

Effect of antibiotic treatment on serum PSA and percent free PSA levels in patients with biochemical criteria for prostate biopsy and previous lower urinary tract infections

BACKGROUND: Controversy exists as to the influence of inflammatory foci on total and free prostate-specific antigen (PSA) concentrations. The objective was to analyze the biological variations of PSA and percent free PSA (%f-PSA) in patients with biochemical criteria for prostate biopsy (PSA higher than 4 ng/mL and normal rectal examination) and compare them with the variation induced by antibiotic treatment in a cohort of patients with a history of lower urinary tract infections and no clinical evidence of prostatitis. METHODS: Ninety patients with a history of lower urinary tract infections, non-suspicious digital rectal examination and PSA between 4 and 20 ng/mL were analyzed. PSA concentration and %f-PSA were determined. Forty-five patients were treated with three weeks of ofloxacin, following which marker determination was repeated. All patients underwent ultrasound-controlled transrectal six-core prostate biopsy. RESULTS: Sixty-seven patients presented benign prostatic hyperplasia (BPH) (30 with prostatitic foci) and 23 cancer. Significant variations in PSA (6.97 ng/mL vs. 5.82 ng/mL, p=0.001) and %f-PSA (14.84% vs. 17.53%, p=0.01) were found only in the treated patients. These differences were significant for patients with BPH-associated prostatitic foci and not for patients with BPH or cancer. The tendency was for PSA to decrease (15 treated patients with PSA <4 ng/mL vs. six non-treated patients) and for %f-PSA to increase. The median variation of %f-PSA was greater than that of PSA. When the cutoff for %f-PSA was set at 25%, 18.9% of unnecessary biopsies after the first determination and 20% after the second could be avoided. By associating the reduction in PSA, up to 46% could be avoided in treated patients. CONCLUSION: Biochemical criteria for prostate biopsy may be modified in patients with a history of lower urinary tract infections due to variations greater than those explained by intraindividual biological variations, and may be influenced by the antibiotic treatment. These results suggest that subclinical inflammatory foci may influence PSA and %f-PSA.     

Clinical utility of prostatic specific antigen and prostatic acid phosphatase serum levels in monitoring prostate cancer

We analysed 696 prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) serum samples by double antibody radioimmunoassay (RIA)I125 in the follow-up of 122 patients with prostate cancer under treatment. PSA levels were significantly correlated to response to treatment, whereas PAP results did not differentiate patients with partial or complete remission. Progression of the disease was detected in 95.2 and 85.4% of PSA and PAP samples, and increased to 99.9% using both simultaneously. On the whole, PSA was better than PAP in monitoring prostate cancer, and the efficacy was greater using both markers together.     

Cancer de la prostate : la maladie localisée

Localized prostate cancer is characterized by a tumor confined to the prostate gland at clinical evaluation. Since the onset of PSA screening, the detection of localized prostate cancer has increased. Prognosis factors are clinical stadification, PSA value, PSA doubling time, tumor volume related to needle biopsy pathologic findings (Gleason score, percentage biopsies involved). Treatment depends on tumor prognosis, symptoms and performance status of the patient. Localized prostate cancer can be treated by surgery (radical prostatectomy, high intensity focused ultrasound) or radiotherapy (conformational radiation therapy, brachytherapy). Active follow-up can be proposed to very low risk patients.     

Problème diagnostique posé par une lésion hépatique hypermétabolique en TEP à la fluorocholine (18F) : à propos d’un cas

IntroductionWe report a case of atypical fluorocholine (18F) PET/CT hypermetabolic hepatic lesion discovered during the staging of a prostate carcinoma.Case reportBecause of elevated PSA serum level, the patient had prostate biopsies which elicited an adenocarcinoma with a Gleason score of 8 (4 + 4). Pelvic MRI did not display any extracapsular disease extension. The PET/CT scan demonstrated a prostatic focal uptake and a liver increased uptake area matching with a segment VII hepatic nodule measuring 25 mm within a fatty liver, which was hypometabolic on the PET scan and hypodense on the CT scan. The liver ultrasound study reported the lesion as a focal spared area of healthy liver tissue within steatosis, whereas MRI diagnostic conclusion was inflammatory hepatocellular adenoma. When asking the patient, it appeared that the hepatic nodule had been known for 7 years, its size was unchanged, and, from previous radiologic imaging, it had been considered as an adenoma. However, there was no histological proof.DiscussionIn the interpretation of the PET/CT scan findings, we excluded a hepatocellular carcinoma and a prostate metastasis due to the long period of time during which the nodule had been followed up without significant change. We thought that focal nodular hyperplasia, which is fluorocholine avid, was the most likely diagnosis, knowing that hepatocellular adenomas, including the inflammatory type, have not been reported to display increased fluorocholine uptake. We noticed that the patient's fatty liver uptake was low, which could have accounted for a falsely increased uptake by the nodule. But, similarly to other authors, we could not find any relationship between CT density and fluorocholine uptake.ConclusionThis case shows a discrepancy between the radiologic and nuclear medicine findings. However, this hepatic nodule is likely to be benign because of the lesion characteristics and the patient medical history.     

Optimisation de l’utilisation du PSA

PSA is a tumor marker usually determined for prostate cancer at diagnosis for its pronostic value and at therapy follow-up. But lack of specificity of PSA for prostate cancer and variability between assays demonstrated by the quality program survey make this marker not valuable in mass screening program. Market control of Afssaps on analysis devices of PSA showed a correct harmonization for total PSA. Biological tools available and easy to perform could improve ability of PSA for early detection of prostate cancer at a curable stage without induction of unnecessary biopsies prescribed because elevated total PSA values.