Quantitative Evaluation of Apparent Diffusion Coefficient Values, ISUP Grades and Prostate-Specific Antigen Density Values of Potentially Malignant PI-RADS Lesions.

The aim of this study was to demonstrate the correlation between ADC values and the ADC/PSAD ratio for potentially malignant prostate lesions classified into ISUP grades and to determine threshold values to differentiate benign lesions (noPCa), clinically insignificant (nsPCa) and clinically significant prostate cancer (csPCa). We enrolled a total of 403 patients with 468 prostate lesions, of which 46 patients with 50 lesions were excluded for different reasons. Therefore, 357 patients with a total of 418 prostate lesions remained for the final evaluation. For all lesions, ADC values were measured; they demonstrated a negative correlation with ISUP grades (p < 0.001), with a significant difference between csPCa and a combined group of nsPCa and noPCa (ns-noPCa, p < 0.001). The same was true for the ADC/PSAD ratio, but only the ADC/PSAD ratio proved to be a significant discriminator between nsPCa and noPCa (p = 0.0051). Using the calculated threshold values, up to 31.6% of biopsies could have been avoided. Furthermore, the ADC/PSAD ratio, with the ability to distinguish between nsPCa and noPCa, offers possible active surveillance without prior biopsy.

Prostate Cancer Detection with mpMRI According to PI-RADS v2 Compared with Systematic MRI/TRUS-Fusion Biopsy: A Prospective Study.

Background: mpMRI assesses prostate lesions through their PI-RADS score. The primary goal of this prospective study was to demonstrate the correlation of PI-RADS v2 score and the volume of a lesion with the presence and clinical significance of prostate cancer (PCa). The secondary goal was to determine the extent of additionally PCa in inconspicuous areas. Methods: All 157 patients underwent a perineal MRI/TRUS-fusion prostate biopsy. Targeted biopsies as well as a systematic biopsy were performed. The presence of PCa in the probes was specified by the ISUP grading system. Results: In total, 258 lesions were biopsied. Of the PI-RADS 3 lesions, 24% were neoplastic. This was also true for 36.9% of the PI-RADS 4 lesions and for 59.5% of the PI-RADS 5 lesions. Correlation between ISUP grades and lesion volume was significant (p < 0.01). In the non-suspicious mpMRI areas carcinoma was revealed in 19.7% of the patients. Conclusions: The study shows that the PI-RADS v2 score and the lesion volume correlate with the presence and clinical significance of PCa. However, there are two major points to consider: First, there is a high number of false positive findings. Second, inconspicuous mpMRI areas revealed PCa.

Ampicillin Treatment of Intracellular Listeria monocytogenes Triggers Formation of Persistent, Drug-Resistant L-Form Cells.

Listeria monocytogenes is an opportunistic intracellular pathogen causing an infection termed listeriosis. Despite the low incidence of listeriosis, the high mortality rate in individuals at risk makes this bacterium one of the most dangerous foodborne pathogens. Reports about a relapse of infection after antibiotic treatment suggest that the bacteria may be able to evade antibiotic treatment and persist as a dormant, antibiotic-tolerant subpopulation. In this study, we observed intracellular generation of antibiotic-resistant L-forms of Listeria monocytogenes following Ampicillin treatment of Listeria monocytogenes infected cells. Detection and identification of intracellular Listeria L-forms was performed by a combination of fluorescence in-situ hybridization and confocal laser scanning microscopy. Using micromanipulation, it was possible to isolate single intracellular L-form cells that following transfer into fresh medium gave rise to pure cultures. In conclusion, the results obtained here provide strong evidence that antibiotic treatment of infected host cells can induce the formation of L-forms from intracellular Listeria monocytogenes. Furthermore, our results suggest that intracellular L-forms persist inside host cells and that they represent viable bacteria, which are still able to grow and proliferate.

Severe Congenital Adrenal Hyperplasia Presenting as Bilateral Testicular Tumors and Azoospermia in the Third Decade of Life.

Classic forms of 21-hydroxylase deficiency (21OHD) are usually diagnosed at birth by salt wasting or precocious puberty in male patients. Here we report the case of a 32-year-old male patient who presented with azoospermia and bilateral testicular tumors. He was referred to our endocrine unit after testicular surgery. His gonadotropins were undetectable. Liquid chromatography-tandem mass spectrometry revealed a high serum progesterone level, high 17-hydroxyprogesterone (17OHP) (255 ng/mL), and high levels of 17OHP metabolites, suggesting a classic form of 21OHD. His blood pressure was normal. Molecular analysis showed a homozygous large 21-hydroxylase gene (CYP21A2) conversion. Furthermore, an adrenal CT scan revealed voluminous, heterogeneous bilateral and asymmetric adrenal masses containing calcifications. Our case report illustrates the fact that a classic form of 21OHD can be diagnosed in late adulthood, manifested by azoospermia and large adrenal tumors, associated with elevated 17OHP.

Influence of acetylsalicylic acid and low-molecular weight heparins on the formation of renal hematoma after shock wave lithotripsy.

PURPOSE: To investigate the risk of renal hematoma (RHT) after shock wave lithotripsy (SWL) among patients on acetylsalicylic acid (ASA) or low-molecular-weight heparin (LMWH). PATIENTS AND METHODS: Retrospective analysis of 434 patients treated with SWL for nephrolithiasis and ureterolithiasis of the proximal ureter. Primary endpoint was detection of RHT by ultrasound the day after SWL. Secondary outcome variables included transfusion of erythrocyte concentrate(s), interventions, hospital readmission or death due to RHT within 30 days of SWL. Binary logistic regression analysis was used including a post hoc one-way analysis. RESULTS: Of 434 patients, 33 (7.6%) and 67 (15.4%) patients were medicated with ASA and LMWH, respectively. RHT was detected in 20 of 434 (4.6%) patients. Of those, 3 (20%) were on ASA, 6 (35%) were on LMWH, 1 (5%) was on ASA and LMWH, and 10 (50%) had no anticoagulation. Univariate analysis showed a statistically significant higher risk for RHT among patients on ASA (p = 0.04) and LWMH (p = 0.02) with an untreated urinary tract infection (UTI) (p = 0.008) and history of cardiovascular disease (p = 0.028). On multivariate analysis, ASA medication, untreated UTI (OR 4.4, 95% CI 1.31-14.75, p = 0.016 and OR 5.79, 95% CI 1.65-20.32, p = 0.03) and a therapeutic dose of LMWH (OR 10.4, 95% CI 1.74-62.27, p = 0.01) were independent predictors for RHT. CONCLUSIONS: Before SWL, a patient risk profile should be evaluated. If feasible, LMWH in therapeutic dosing should be avoided, and ASA should be discontinued. UTI should be treated before SWL in any case. TRIAL REGISTRATION: http://www.clinicaltrials.gov ; Identifier NCT02875717.

Modeling therapeutic response to radioiodine in metastatic thyroid cancer: a proof-of-concept study for individualized medicine.

PURPOSE: Radioiodine therapy (RAI) has traditionally been used as treatment for metastatic thyroid cancer, based on its ability to concentrate iodine. Propositions to maximize tumor response with minimizing toxicity, must recognize the infinite possibilities of empirical tests. Therefore, an approach of this study was to build a mathematical model describing tumor growth with the kinetics of thyroglobulin (Tg) concentrations over time, following RAI for metastatic thyroid cancer. EXPERIMENTAL DESIGN: Data from 50 patients with metastatic papillary thyroid carcinoma treated within eight French institutions, followed over 3 years after initial RAI treatments, were included in the model. A semi-mechanistic mathematical model that describes the tumor growth under RAI treatment was designed. RESULTS: Our model was able to separate patients who responded to RAI from those who did not, concordant with the physicians' determination of therapeutic response. The estimated tumor doubling-time (Td was found to be the most informative parameter for the distinction between responders and non-responders. The model was also able to reclassify particular patients in early treatment stages. CONCLUSIONS: The results of the model present classification criteria that could indicate whether patients will respond or not to RAI treatment, and provide the opportunity to perform personalized management plans.

BK virus associated pronounced hemorrhagic cystoureteritis after bone marrow transplantation.

Ureteral stenosis due to reactivation of the BK virus (BKV) in a state of immunodeficiency is very rare. More common is the appearance of a hemorrhagic cystitis. This report not only shows bilateral ureteral stenosis after bone marrow transplantation, but also presents severe complications as chronic pelvic pain and impaired kidney function as well as irreparable damage to the whole urinary tract leading to nephroureterectomy, subtrigonal cystectomy and orthotopic ileal neobladder. Finally renal transplantation was required. To our knowledge this is the first case in the literature where such a severe course of BKV associated hemorrhagic cystoureteritis is described.

[Urinary incontinence - what can be done by the family doctor and when is the urologist needed?]. / Harninkontinenz - was kann der Grundversorger machen und wann braucht es den Urologen?

About 15% of the women and 10% of the men past the age of 65 years suffer from urinary incontinence. In most cases, accurate history taking can help differentiate between urge incontinence, stress incontinence and overflow incontinence, and is essential in choosing the appropriate treatment. Initial diagnostic testing can be conducted by the general practitioner, especially tests to exclude urinary tract infections or to rule out an overactive bladder. Patient education on changes to fluid intake and voiding habits as well as advice on suitable incontinence products are important first steps in the management of urinary continence. Also, drug treatment can be initiated in general practice. Patients with refractory urinary incontinence, particularly those who did not respond to anticholinergic medication, should be referred to a urologist for further evaluation since there may be an underlying tumour or other disorder of the bladder that is causing the incontinence.

Environ 15% des femmes et 10% des hommes âgée de plus de de 65 ans souffrent d'incontinence urinaire. Dans le plupart des cas, une anamnèse soigneuse peut aider à différencier entre l'incontinence par impériosité, l'incontinence de stress et l'incontinence par regorgement, ce qui est essentiel pour choisir le traitement approprié. L'évaluation diagnostique initiale peut être effectuée par le médecin généraliste, en particulier les tests pour exclure une infection urinaire ou une incontinence par regorgement. L'éducation des malades visant à changer les habitudes de prise liquidienne et d'uriner, ainsi qu'à conseiller des produits appropriés à l'incontinence représente une importante première étape dans la prise en charge de ce problème. Le traitement médicamenteux peut également être instauré en pratique générale. Les malades ayant une incontinence urinaire réfractaire, en particulier ceux qui ne répondent pas à un anticholinergique, devraient être référés à un urologue pour étendre les investigations puisqu'une tumeur sous-jacente ou une autre anomalie de la vessie peut être responsable de l'incontinence.

Increased serum thyroglobulin levels and negative imaging in thyroid cancer patients: are there sources of benign secretion? A speculative short review.

After thyroidectomy and 131I ablation for differentiated thyroid cancer (DTC), serum thyroglobulin (Tg) became a sensitive marker of residual disease. It is not uncommon to find patients at follow-up with persistent serum Tg levels and no other clinical or imaging evidence for the disease. The vast majority of these patients, most probably, have occult foci of disease, often in minute cervical lymph nodes. A review of the literature including papers published on PubMed/Medline until June 2010 was made. In this study we speculated that a minority of patients who had undergone surgery for differentiated thyroid cancer might have benign sources of Tg secretion at follow-up. These sources may be foci of radio-resistant ectopic thyroid tissue or a thyroid stimulating hormone-stimulated thymus.

Parathyroid scintigraphy findings in chronic kidney disease patients with recurrent hyperparathyroidism.

BACKGROUND: Parathyroidectomy (PTX), either subtotal or total with forearm autografting, is a well-established treatment for refractory renal hyperparathyroidism (RHPT). However, 20-30% of patients develop persistent or recurrent disease. Obtaining accurate localization before reoperation is difficult. PATIENTS AND METHODS: The study group comprised 21 consecutive adult patients (18 undergoing haemodialysis and 3 with a renal graft) imaged using (99m)Tc-sestamibi/(123)I subtraction scintigraphy. Of the 21 patients, 12 had undergone one previous PTX and the other 9 between two and four parathyroid operations. All patients had symptoms and signs of severe RHPT. The mean serum PTH level was 1,142 pg/ml. (99m)Tc-Sestamibi and (123)I images were recorded simultaneously. Imaging views comprised a planar view of the neck and mediastinum, followed by a magnified pinhole view over the thyroid bed area. If parathyroid ectopy was detected, SPECT or SPECT-CT was performed. The forearm was imaged in case of autograft. RESULTS: Parathyroid scintigraphy was negative in one patient and positive in the other 20 (sensitivity 95.2%). One patient had uptake corresponding to two unresected parathyroid glands. Recurrence at the site of the partially resected gland or autograft was seen in 11 patients. However, six of them had a second (99m)Tc-sestamibi focus corresponding to a supernumerary parathyroid gland. Seven other patients had a supernumerary parathyroid gland as the sole cause of relapse. Three of the supernumerary glands showed major ectopy (intrathyroidal, low mediastinal, undescended within the vagus nerve). One patient had parathyromatosis with multiple parathyroid nodules scattered over the left side of the neck. Reoperation was possible in 13 patients, with no false-positive findings. CONCLUSION: Many patients referred with the hypothesis of hyperplasia of a subtotally resected parathyroid gland or autograft were found to harbour a supernumerary parathyroid gland missed at the initial surgery.

Scintigraphic visualization of glossal thyroid tissue during the follow-up of thyroid cancer patients.

PURPOSE: Nests of thyroid tissue in the tongue are described in about 10% of necropsies. This ectopic thyroid tissue usually lies dormant, but may manifest itself during times of increased stimulation. The aim of our study was to assess the frequency of lingual thyroid visualization on I-131 diagnostic whole-body scan during the follow-up of thyroid cancer patients. MATERIAL AND METHODS: We reviewed the files of 548 consecutive patients who underwent a diagnostic whole-body scan with 200 MBq of I-131 between January 2000 and December 2005, as part of the follow-up for a differentiated thyroid cancer. Every patient had been previously treated with a total thyroidectomy and had received 3.7 GBq (100 mCi) of I-131 for remnant ablation. RESULTS: A focus of uptake located between the 2 submandibular salivary glands, suggestive of ectopic thyroid tissue in the tongue or in the upper part of the thyroglossal duct, was found in 5 of the 548 patients (0.9%). In only one of these patients was the uptake visible at the time of postsurgery thyroid remnant ablation scan. Thyroglobulin (Tg) levels were positive under stimulation in 3 of the 5 patients, and another patient had undetectable Tg, but positive anti-Tg antibodies. Radiologic imaging (MRI and/or ultrasound) was performed in 3 patients and confirmed the presence of a mass suggestive of ectopic thyroid tissue in two. Invasive lingual biopsy was not performed to verify the benign nature. CONCLUSION: When examining whole-body scans (therapeutic or diagnostic) in a patient with persistent Tg detection after thyroid ablation, one should carefully search for any uptake between the submandibular glands that may be suggestive of ectopic tissue.

Bone metastases of differentiated thyroid cancer: impact of early 131I-based detection on outcome.

Bone is the second most frequent target of distant metastases in patients with differentiated thyroid cancer, and such forms carry a very poor prognosis. The impact of (131)I therapy in this setting is controversial. We describe the diagnostic circumstances and outcome of patients with bone metastases recently managed in two institutions. Among 921 consecutive thyroid cancer patients who had total thyroidectomy and (131)I ablation between January 2000 and December 2004 and who were subsequently monitored, bone metastases had been diagnosed in 16 patients. In three cases, the bone metastases were non-functioning (negative (131)I uptake) . These patients were treated with surgery and radiotherapy but progressed rapidly. The other 13 patients had functioning (positive (131)I uptake) bone metastases. In five of them, thyroid cancer was revealed by signs of distant involvement (bone pain, n = 4; dyspnea, n = 1). The bone metastases progressed in these five patients, despite local therapy and multiple courses of (131)I. The bone metastases in the remaining eight patients were discovered on the post-surgery (131)I therapy scan. Complementary radiological studies were negative except in one patient in whom one of the metastases (a 5 mm lesion of the right humerus) was visible on magnetic resonance imaging (MRI). Six of these patients showed a good response to (131)I therapy, with (131)I uptake and Tg levels becoming undetectable or showing a sharp fall. One patient refused (131)I therapy; bone metastases became visible on MRI within 1 year and the Tg level rose tenfold. The disease progressed in one patient despite (131)I therapy. Post-surgical (131)I ablation can contribute to early detection of bone metastases at a time when the Tg level may be only moderately elevated, when other radiological studies are negative, and when the disease is potentially curable by (131)I therapy.

Stimulation test in the follow-up of thyroid cancer: plasma rhTSH levels are dependent on body weight, not endogenously stimulated TSH values.

BACKGROUND: Stimulation testing in the first year following thyroid ablation has important prognostic value in thyroid cancer patients. Recombinant human TSH (rhTSH) is better tolerated than thyroid hormone withdrawal but provides only transient stimulation so that the TSH threshold of 30 mIU x l(-1) which defines adequate testing during thyroid hormone withdrawal is not appropriate for rhTSH stimulation. We looked at rhTSH levels after a standard two intramuscular injections of 0.9 mg rhTSH. METHODS: Plasma rhTSH levels were measured 24 h after the second injection in 143 consecutive patients. RESULTS: rhTSH levels showed large inter-patient variation (range: 44-240; mean+/-SD: 131+/-48). There was a strong inverse correlation between TSH levels and body weight (P<0.001). Levels lower than 80 mIU x l(-1) (corresponding to 1 SD below average) were recorded in 24 patients (16.8%). These patients had an average body weight of 79.7 kg, as compared to 67.9 kg for those patients with TSH levels higher than 80 mIU x l(-1). A withdrawal test in the first year after thyroid ablation was available in 64 patients. Only one patient (1.6%) had inadequate endogenous TSH stimulation, and there was no dependence of endogenous plasma TSH levels upon weight. CONCLUSION: Contrary to endogenous stimulation, TSH levels after rhTSH injection vary with body weight. The dosage of rhTSH may need to be adapted in patients with more than 80 kg body weight.

Should 'low-risk' thyroid cancer patients with residual thyroglobulin be re-treated with iodine 131?

OBJECTIVE: The American consensus statement on patients with low-risk thyroid cancer, published in 2003, suggests repeat (131)I therapy if the thyroglobulin value is elevated at first follow-up. We evaluated this strategy in our practice. METHODS: Among 407 patients with thyroid cancer who had total thyroidectomy and (131)I ablation between January 2000 and December 2003, 12 patients with stage I thyroid cancer (any tumour (T), any node (N), metastasis (M)0 if < 45 years or T1, N0, M0 if > 45 years), were re-treated on the basis of their thyroglobulin level at first follow-up. Mean patient age was 32.8 years. None of them had a T4 tumour. Thyroglobulin levels after thyroid hormone withdrawal 'off-T4' ranged between 4.5 and 251 ng/ml (median 8). One to four courses of 3.7 GBq (131)I were given. RESULTS: Three patients had a negative (131)I therapy scan and an uneventful course. Two patients had slight residual uptake only in the thyroid bed and negative ultrasound examination. Four patients had isolated (131)I uptake in the mediastinal region. No abnormalities were found on complementary mediastinal imaging. This finding was interpreted as benign (131)I thymic uptake. The last three patients also had mediastinal thymic uptake associated with a slight thyroid bed uptake. One patient had a gradual increase in the thyroglobulin level, and underwent resection of nonfunctioning neck lymph nodes. Thyroglobulin levels declined in all other patients. CONCLUSIONS: No distant lesions were found in a group of young 'low-risk' thyroid cancer patients given empirical (131)I therapy for residual thyroglobulin. When blind (131)I therapy shows no uptake, or uptake limited to the thymus, (131)I therapy should not be repeated. The authors also briefly discuss the hypothesis that enhanced thymus might be a source of benign thyroglobulin secretion.

Which thyroid cancer patients need periodic stimulation tests?

PURPOSE: Recurrences are frequent in thyroid cancer patients and long-term follow-up is therefore necessary. We evaluated the yield of rhTSH stimulation in three groups of patients, classified according to the UICC/TNM risk stratification and the results of first follow-up testing. METHODS: The study population comprised 129 patients referred for rhTSH testing. All had undergone first follow-up testing after thyroid hormone withdrawal (off-T4) within 1 year of 131I ablation. Negative first follow-up testing was defined as Tg <2 ng/ml and no neck uptake on 131I diagnostic whole-body scan. Seventy-five patients had stage I thyroid cancer and negative first follow-up testing (group A), 19 had stage I disease and positive first follow-up testing (group B), and 35 had stage II-IV disease (group C). RhTSH stimulation was performed an average of 6 years after first follow-up testing. RESULTS: 131I diagnostic scanning after rhTSH was negative in all 75 group A patients. Only one group A patient had detectable Tg after rhTSH injection (1.5 ng/ml), but Tg had also been detected at baseline in this patient (1.45 ng/ml). Given the absence of a response to stimulation, suggesting an interference, Tg was reassessed with a different technique and proved to be undetectable (<0.1 ng/ml). Stimulation with rhTSH in group B showed residual Tg in seven patients and residual 131I uptake in the thyroid bed in two patients, but none of these patients had signs of disease progression. Five group C patients (14%) had a positive rhTSH test result, and this was suggestive of disease progression in at least two cases. CONCLUSION: The first follow-up testing is essential for prognostic classification after 131I ablation of thyroid cancer. In stage I patients, undetectable Tg and negative 131I scan 1 year after ablation define a large population of subjects who have a very low risk of recurrence and who do not require further stimulation tests. In contrast, periodic rhTSH stimulation tests appear useful in higher-risk patients.