1
|
da Silva Filho AC, Rocha TO, Elias J, Barros MVDC, Silva AR, Dos Reis RB, Muglia VF. Value of adding the apparent diffusion coefficient to capsular contact for the prediction of extracapsular extension in prostate cancer. Radiol Bras 2020; 53:381-389. [PMID: 33304005 PMCID: PMC7720667 DOI: 10.1590/0100-3984.2019.0123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Objective To determine whether evaluating the mean apparent diffusion coefficient (ADC) together with capsular contact (CC) adds value in the prediction of microscopic extracapsular extension (ECE) of prostate cancer. Materials and Methods Between January 2012 and December 2016, 383 patients underwent multiparametric magnetic resonance imaging (mpMRI) of the prostate. A total of 67 patients were selected for inclusion. Two radiologists (observers 1 and 2), working independently, performed qualitative and quantitative analyses of ECE, macroscopic ECE, and microscopic ECE. A third radiologist assessed the correlation with the clinical data, and two experienced pathologists reviewed all histopathological findings. Results Among the 67 patients, mpMRI showed lesions that were confined to the capsule in 44 (66.7%), had microscopic ECE in 12 (17.9%), and had macroscopic ECE in 11 (16.4%). There were no significant differences, in terms of the diagnostic accuracy, as measured by determining the area under the curve (AUC), of CC on T2-weighted images (CCT2), CC on diffusion-weighted imaging (CCDWI), and the mean ADC for the prediction of microscopic ECE, between observer 1 (AUC of 0.728, 0.691, and 0.675, respectively) and observer 2 (AUC of 0.782, 0.821, and 0.799, respectively). Combining the mean ADC with the CCT2 or CCDWI did not improve the diagnostic accuracy for either observer. There was substantial interobserver agreement for the qualitative evaluation of ECE, as demonstrated by the kappa statistic, which was 0.77 (0.66-0.87). The diagnostic accuracy (AUC) of the qualitative assessment for predicting microscopic ECE was 0.745 for observer 1 and 0.804 for observer 2, and the difference was less than significant. In a multivariate analysis, none of clinical or imaging parameters were found to be associated with ECE. Conclusion For the detection of microscopic ECE on mpMRI, CC appears to have good diagnostic accuracy, especially if the observer has considerable experience. Adding the mean ADC to the CCT2 or CCDWI does not seem to provide any significant improvement in that diagnostic accuracy.
Collapse
Affiliation(s)
| | - Tamara Oliveira Rocha
- Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil
| | - Jorge Elias
- Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil
| | | | - Alfredo Ribeiro Silva
- Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil
| | - Rodolfo Borges Dos Reis
- Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil
| | - Valdair Francisco Muglia
- Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil
| |
Collapse
|
2
|
Pallavi UN, Gogoi S, Thakral P, Malasani V, Sharma K, Manda D, Das SS, Pant V, Sen I. Incremental Value of Ga-68 Prostate-Specific Membrane Antigen-11 Positron-Emission Tomography/Computed Tomography Scan for Preoperative Risk Stratification of Prostate Cancer. INDIAN JOURNAL OF NUCLEAR MEDICINE : IJNM : THE OFFICIAL JOURNAL OF THE SOCIETY OF NUCLEAR MEDICINE, INDIA 2020; 35:93-99. [PMID: 32351261 PMCID: PMC7182336 DOI: 10.4103/ijnm.ijnm_189_19] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 11/20/2019] [Accepted: 01/18/2020] [Indexed: 11/06/2022]
Abstract
Background: Prostate cancer (PC) is the second-most common cause of cancer.68Ga-prostate-specific membrane antigen (PSMA)-11 positron-emission tomography/computed tomography (PET/CT) scan help in accurate staging of PC owing to its high PSMA avidity and specificity. The aim of this prospective observational study was to determine the incremental value of Ga-68 PSMA-11 PET/CT over multiparametric magnetic resonance imaging (mpMRI) in the locoregional staging of intermediate- and high-risk PC using histopathology from radical prostatectomy specimens as a gold standard. Materials and Methods: This was a prospective study, including 35 patients with biopsy-proven prostate carcinoma. All the patients underwent whole-body Ga-68 PSMA-11 PET/CT scans along with mpMRI including a dedicated pelvic imaging protocol within a time window of ± 10 days. The reference standard was based on histopathological results, postprostatectomy. Results: All 35 patients showed Ga-68 PSMA-11-avid disease, of which 29 underwent radical prostatectomy, one underwent radiation therapy, and five did not undergo surgery owing to metastases. A total of 52 PC lesions were detected in 29 patients on histopathology. Of 52 lesions, 29 lesions were identified in prostate parenchyma and 23 were extraprostatic lesions on histopathology. Ga-68 PSMA-11 PET/CT detected a total of 45 lesions, of which 29 lesions were located within the prostate parenchyma and 16 were representative of extraprostatic lesions. mpMRI detected a total of 36 lesions, of which 29 lesions were located within the prostate parenchyma and seven were representative of extraprostatic lesions. The overall sensitivity of 68Ga-PSMA PET/CT and mpMRI in the detection of lesions was 86.2% and 68.6%, respectively. However, the overall specificity was 94.7% and 89.1% for 68Ga-PSMA and mpMRI, respectively. Conclusion: Ga-68 PSMA-11 PET/CT provided superior locoregional preoperative staging of PC as compared to mpMRI in intermediate- and high-risk PC patients.
Collapse
Affiliation(s)
- U N Pallavi
- Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India
| | - Sanjay Gogoi
- Department of Urology, Manipal Hospitals, New Delhi, India
| | - Parul Thakral
- Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India
| | - Vindhya Malasani
- Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India
| | - Kanchan Sharma
- Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India
| | - Divya Manda
- Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India
| | - Subha Shankar Das
- Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India
| | - Vineet Pant
- Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India
| | - Ishita Sen
- Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India
| |
Collapse
|
3
|
Low PI-RADS assessment category excludes extraprostatic extension (≥pT3a) of prostate cancer: a histology-validated study including 301 operated patients. Eur Radiol 2019; 29:5478-5487. [PMID: 30887199 PMCID: PMC6719329 DOI: 10.1007/s00330-019-06092-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 01/31/2019] [Accepted: 02/08/2019] [Indexed: 01/21/2023]
Abstract
OBJECTIVES To evaluate whether low PI-RADS v2 assessment categories are effective at excluding extraprostatic extension (EPE) of prostate cancer (≥pT3a PCa). METHODS The local institutional ethics committee approved this retrospective analysis of 301 consecutive PCa patients. Patients were classified as low- or intermediate/high-risk based on clinical parameters and underwent pre-surgical multiparametric magnetic resonance imaging. A PI-RADS v2 assessment category and ESUR EPE score were assigned for each lesion by two readers working in consensus. Histopathologic analysis of the whole-mount radical prostatectomy specimen was the reference standard. Univariate and multivariate analyses were performed to evaluate the association of PI-RADS v2 assessment category with final histology ≥pT3a PCa. RESULTS For a PI-RADS v2 assessment category threshold of 3, the overall performance for ruling out (sensitivity, negative predictive value, negative likelihood ratio) ≥pT3a PCa was 99%/98%/0.04 and was similar in both the low-risk (96%/97%/0.12; N = 137) and the intermediate/high-risk groups (100%/100%/0.0; N = 164). In univariate analysis, all clinical and tumor characteristics except age were significantly associated with ≥pT3a PCa. In multivariate analysis, PI-RADS v2 assessment categories ≤ 3 had a protective effect relative to categories 4 and 5. The inclusion of ESUR EPE score improved the AUC of ≥pT3a PCa prediction (from 0.73 to 0.86, p = 0.04 in the overall cohort). The impact of PI-RADS v2 assessment category is reflected in a nomogram derived on the basis of our cohort. CONCLUSIONS In our cohort, low PI-RADS v2 assessment categories of 3 or less confidently ruled out the presence of ≥pT3a PCa irrespective of clinical risk group. KEY POINTS • Our analysis of 301 mp-MRI and RARP specimens showed that the addition of PI-RADS v2 assessment categories to clinical parameters improves the exclusion of ≥pT3a (extraprostatic) prostate cancer. • PI-RADS v2 assessment categories of 1 to 3 are useful for excluding ≥pT3a prostate cancer with a NPV of 98%; such patients can be considered as candidates for less invasive approaches. • The ability to exclude ≥pT3a prostate cancer may improve confidence in choosing nerve-sparing surgery or in avoiding pelvic nodal dissections, and similarly for patients undergoing radiotherapy, in adopting short-course adjuvant hormonal therapy or foregoing prophylactic nodal irradiation.
Collapse
|
4
|
Affiliation(s)
- Baris Turkbey
- Molecular Imaging Program, National Cancer Institute, National Institutes of Health Bethesda, Maryland, USA.
| | | |
Collapse
|
5
|
Van Holsbeeck A, Degroote A, De Wever L, Vanhoutte E, De Keyzer F, Van Poppel H, Oyen R. Staging of prostatic carcinoma at 1.5-T MRI: correlation of a simplified MRI exam with whole-mount radical prostatectomy specimens. Br J Radiol 2016; 89:20160101. [PMID: 27181821 DOI: 10.1259/bjr.20160101] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE To retrospectively analyze the accuracy of simplified multiparametric MRI at 1.5 T for local staging by using whole-mount-section histopathological analysis as the standard of reference. METHODS 123 consecutive patients underwent T2 weighted, T1 weighted and diffusion-weighted MRI without endorectal coil prior to radical prostatectomy. The accuracy of predicting extracapsular extension (ECE) (T3a) was assessed using direct signs or the combination of direct and indirect signs of extraprostatic extension. The accuracy of predicting seminal vesicle invasion (T3b) was evaluated, taking into account different routes of seminal vesicle involvement. Finally, adjacent organ invasion (T4) was evaluated in this patient population. RESULTS Histopathology showed T3a, T3b and T4 in 61, 28 and 9 cases, respectively. The use of direct signs of extraprostatic extension showed a sensitivity of 57.4% and specificity of 91.9%. The combination of direct signs and indirect signs improved sensitivity (85.2%) at the expense of moderate loss of specificity (83.9%). MR sensitivity for the detection of seminal vesicle invasion was low (53.6%); however, it was dependent on the route of seminal vesicle tumour infiltration. MR sensitivity and specificity for adjacent organ invasion were 88.9% and 99.1%. CONCLUSION Simplified MRI study at 1.5 T provides a relatively high sensitivity for detecting ECE (T3a) when using the combination of indirect and direct signs. However, this high sensitivity reading is at the cost of a moderate loss of specificity. Invasion of the seminal vesicles (T3b) occurs most often along the ejaculatory duct complex with low MR sensitivity. ADVANCES IN KNOWLEDGE Simplified MRI study at 1.5 T without endorectal coil could be used for the local T staging of prostate cancer.
Collapse
Affiliation(s)
| | - Annemarie Degroote
- 2 Department of Histopathology, University Hospitals Leuven, Leuven, Belgium
| | - Liesbeth De Wever
- 1 Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | - Els Vanhoutte
- 1 Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | | | | | - Raymond Oyen
- 1 Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| |
Collapse
|
6
|
Sammet S, Partanen A, Yousuf A, Sammet CL, Ward EV, Wardrip C, Niekrasz M, Antic T, Razmaria A, Farahani K, Sokka S, Karczmar G, Oto A. Cavernosal nerve functionality evaluation after magnetic resonance imaging-guided transurethral ultrasound treatment of the prostate. World J Radiol 2015; 7:521-530. [PMID: 26753067 PMCID: PMC4697126 DOI: 10.4329/wjr.v7.i12.521] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Revised: 06/15/2015] [Accepted: 11/25/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the feasibility of using therapeutic ultrasound as an alternative treatment option for organ-confined prostate cancer.
METHODS: In this study, a trans-urethral therapeutic ultrasound applicator in combination with 3T magnetic resonance imaging (MRI) guidance was used for real-time multi-planar MRI-based temperature monitoring and temperature feedback control of prostatic tissue thermal ablation in vivo. We evaluated the feasibility and safety of MRI-guided trans-urethral ultrasound to effectively and accurately ablate prostate tissue while minimizing the damage to surrounding tissues in eight canine prostates. MRI was used to plan sonications, monitor temperature changes during therapy, and to evaluate treatment outcome. Real-time temperature and thermal dose maps were calculated using the proton resonance frequency shift technique and were displayed as two-dimensional color-coded overlays on top of the anatomical images. After ultrasound treatment, an evaluation of the integrity of cavernosal nerves was performed during prostatectomy with a nerve stimulator that measured tumescence response quantitatively and indicated intact cavernous nerve functionality. Planned sonication volumes were visually correlated to MRI ablation volumes and corresponding histo-pathological sections after prostatectomy.
RESULTS: A total of 16 sonications were performed in 8 canines. MR images acquired before ultrasound treatment were used to localize the prostate and to prescribe sonication targets in all canines. Temperature elevations corresponded within 1 degree of the targeted sonication angle, as well as with the width and length of the active transducer elements. The ultrasound treatment procedures were automatically interrupted when the temperature in the target zone reached 56 °C. In all canines erectile responses were evaluated with a cavernous nerve stimulator post-treatment and showed a tumescence response after stimulation with an electric current. These results indicated intact cavernous nerve functionality. In all specimens, regions of thermal ablation were limited to areas within the prostate capsule and no damage was observed in periprostatic tissues. Additionally, a visual analysis of the ablation zones on contrast-enhanced MR images acquired post ultrasound treatment correlated excellent with the ablation zones on thermal dose maps. All of the ablation zones received a consensus score of 3 (excellent) for the location and size of the correlation between the histologic ablation zone and MRI based ablation zone. During the prostatectomy and histologic examination, no damage was noted in the bladder or rectum.
CONCLUSION: Trans-urethral ultrasound treatment of the prostate with MRI guidance has potential to safely, reliably, and accurately ablate prostatic regions, while minimizing the morbidities associated with conventional whole-gland resection or therapy.
Collapse
|
7
|
Garvey B, Türkbey B, Truong H, Bernardo M, Periaswamy S, Choyke PL. Clinical value of prostate segmentation and volume determination on MRI in benign prostatic hyperplasia. Diagn Interv Radiol 2015; 20:229-33. [PMID: 24675166 DOI: 10.5152/dir.2014.13322] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Benign prostatic hyperplasia (BPH) is a nonmalignant pathological enlargement of the prostate, which occurs primarily in the transitional zone. BPH is highly prevalent and is a major cause of lower urinary tract symptoms in aging males, although there is no direct relationship between prostate volume and symptom severity. The progression of BPH can be quantified by measuring the volumes of the whole prostate and its zones, based on image segmentation on magnetic resonance imaging. Prostate volume determination via segmentation is a useful measure for patients undergoing therapy for BPH. However, prostate segmentation is not widely used due to the excessive time required for even experts to manually map the margins of the prostate. Here, we review and compare new methods of prostate volume segmentation using both manual and automated methods, including the ellipsoid formula, manual planimetry, and semiautomated and fully automated segmentation approaches. We highlight the utility of prostate segmentation in the clinical context of assessing BPH.
Collapse
Affiliation(s)
- Brian Garvey
- From the Molecular Imaging Program Nashua, New Hampshire, USA.
| | | | | | | | | | | |
Collapse
|
8
|
Dynamic contrast-enhanced MRI for the detection of prostate cancer: meta-analysis. AJR Am J Roentgenol 2015; 204:W439-48. [PMID: 25794093 DOI: 10.2214/ajr.14.13373] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
OBJECTIVE The purpose of this study was to systematically review and meta-analyze dynamic contrast-enhanced MRI (DCE-MRI) for the detection of prostate cancer in comparison with standard evaluation with T2-weighted imaging. MATERIALS AND METHODS A PubMed electronic database search for the terms "dynamic contrast-enhanced," "prostate," and "MRI" was completed for articles up to September 17, 2013. All included studies had histopathologic correlation. Two by two contingency data were constructed for each study. A binormal bayesian ROC model was used to estimate and compare sensitivity, specificity, and AUC among eligible modalities. RESULTS Both DCE-MRI (0.82-0.86) and diffusion-weighted MRI (DWI) (0.84-0.88) yielded significantly better AUC than T2-weighted imaging (0.68-0.77). Moreover, partial AUC for the combination of DCE-MRI, DWI, and T2-weighted imaging was improved significantly (0.111; 0.103-0.119) when compared with DCE-MRI alone (0.079; 0.072-0.085) and T2-weighted imaging alone (0.079; 0.074-0.084) but not DWI alone (0.099; 0.091-0.108). Sensitivity and specificity were similar among the four modalities. CONCLUSION DCE-MRI improves AUC of tumor detection overall compared with T2-weighted imaging alone. Methods for DCE-MRI analysis require standardization, but visual analysis performs similar to semiquantitative methods. A two-parameter approach using DCE-MRI and T2-weighted imaging or DWI and T2-weighted imaging may be sufficient, and the latter may be more favorable for most routine prostate cancer imaging.
Collapse
|
9
|
Rais-Bahrami S, Turkbey B, Grant KB, Pinto PA, Choyke PL. Role of multiparametric magnetic resonance imaging in the diagnosis of prostate cancer. Curr Urol Rep 2014; 15:387. [PMID: 24430169 DOI: 10.1007/s11934-013-0387-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Prostate cancer is the most common solid-organ malignancy among American men. It is currently most commonly diagnosed on random systematic biopsies prompted by elevated serum PSA levels. Multi-parametric MRI (MP-MRI) of the prostate has emerged as an anatomic and functional imaging modality, which offers accurate detection, localization and staging of prostate cancer. Recently, MP-MRI has gained an increasing role in guiding biopsies to sites of abnormality and in monitoring patients on active surveillance. Here, we discuss the historical development, current role, and potential future directions of MP-MRI in the diagnosis of prostate cancer.
Collapse
Affiliation(s)
- Soroush Rais-Bahrami
- Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10 - CRC, Bethesda, MD, 20892, USA
| | | | | | | | | |
Collapse
|
10
|
Functional MRI in prostate cancer detection. BIOMED RESEARCH INTERNATIONAL 2014; 2014:590638. [PMID: 25215284 PMCID: PMC4158139 DOI: 10.1155/2014/590638] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Accepted: 07/15/2014] [Indexed: 12/20/2022]
Abstract
Multiparametric magnetic resonance imaging (MP-MRI) has emerged as a promising method for the detection of prostate cancer. The functional MRI components of the MP-MRI consist of the diffusion weighted MRI, dynamic contrast enhanced MRI, and magnetic resonance spectroscopic imaging. The purpose of this paper is to review the existing literature about the use of functional MRI in prostate cancer detection.
Collapse
|
11
|
Cullu N, Kantarci M, Ogul H, Adanur S, Okur A, Koc E, Pirimoglu B, Karaca L, Kizrak Y, Polat O. Feasibility study of CT perfusion imaging for prostate carcinoma. Eur Radiol 2014; 24:2236-44. [PMID: 24863884 DOI: 10.1007/s00330-014-3212-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Revised: 03/25/2014] [Accepted: 04/30/2014] [Indexed: 01/01/2023]
Abstract
OBJECTIVE The aim of this feasibility study was to obtain initial data with which to assess the efficiency of perfusion CT imaging (CTpI) and to compare this with magnetic resonance imaging (MRI) in the diagnosis of prostate carcinoma. MATERIALS AND METHODS This prospective study involved 25 patients with prostate carcinoma undergoing MRI and CTpI. All analyses were performed on T2-weighted images (T2WI), apparent diffusion coefficient (ADC) maps, diffusion-weighted images (DWI) and CTp images. We compared the performance of T2WI combined with DWI and CTp alone. The study was approved by the local ethics committee, and written informed consent was obtained from all patients. RESULTS Tumours were present in 87 areas according to the histopathological results. The diagnostic performance of the T2WI+DWI+CTpI combination was significantly better than that of T2WI alone for prostate carcinoma (P < 0.001). The diagnostic value of CTpI was similar to that of T2WI+DWI in combination. There were statistically significant differences in the blood flow and permeability surface values between prostate carcinoma and background prostate on CTp images. CONCLUSION CTp may be a valuable tool for detecting prostate carcinoma and may be preferred in cases where MRI is contraindicated. If this technique is combined with T2WI and DWI, its diagnostic value is enhanced. KEY POINTS Perfusion CT is a helpful technique for prostate carcinoma diagnosis. •Colour maps allow easy and rapid visual assessment of the functional changes. Colour maps of prostate carcinoma provide information about in vivo tumoral vascularity. CTp images may be added into routine radiological examinations. CTp provides guidance for histopathological correlation if biopsy is scheduled.
Collapse
Affiliation(s)
- Nesat Cullu
- Department of Radiology, Muğla Sıtkı Koçman University, School of Medicine, Muğla, Turkey
| | | | | | | | | | | | | | | | | | | |
Collapse
|
12
|
|