A nomogram to predict the absence of clinically significant prostate cancer in males with negative MRI

PURPOSE: To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). MATERIALS AND METHODS: We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. RESULTS: Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. CONCLUSIONS: Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI.

Repeatability and Reproducibility Assessment of the Apparent Diffusion Coefficient in the Prostate: A Trial of the ECOG-ACRIN Research Group (ACRIN 6701).

BACKGROUND: Uncertainty regarding the reproducibility of the apparent diffusion coefficient (ADC) hampers the use of quantitative diffusion-weighted imaging (DWI) in evaluation of the prostate with magnetic resonance imaging MRI. The quantitative imaging biomarkers alliance (QIBA) profile for quantitative DWI claims a within-subject coefficient of variation (wCV) for prostate lesion ADC of 0.17. Improved understanding of ADC reproducibility would aid the use of quantitative diffusion in prostate MRI evaluation. PURPOSE: Evaluation of the repeatability (same-day) and reproducibility (multi-day) of whole-prostate and focal-lesion ADC assessment in a multi-site setting. STUDY TYPE: Prospective multi-institutional. SUBJECTS: Twenty-nine males, ages 53 to 80 (median 63) years, following diagnosis of prostate cancer, 10 with focal lesions. FIELD STRENGTH/SEQUENCE: 3T, single-shot spin-echo diffusion-weighted echo-planar sequence with four b-values. ASSESSMENT: Sites qualified for the study using an ice-water phantom with known ADC. Readers performed DWI analyses at visit 1 ("V1") and visit 2 ("V2," 2-14 days after V1), where V2 comprised scans before ("V2pre") and after ("V2post") a "coffee-break" interval with subject removal and repositioning. A single reader segmented the whole prostate. Two readers separately placed region-of-interests for focal lesions. STATISTICAL TESTS: Reproducibility and repeatability coefficients for whole prostate and focal lesions derived from median pixel ADC. We estimated the wCV and 95% confidence interval using a variance stabilizing transformation and assessed interreader reliability of focal lesion ADC using the intraclass correlation coefficient (ICC). RESULTS: The ADC biases from b0 -b600 and b0 -b800 phantom scans averaged 1.32% and 1.44%, respectively; mean b-value dependence was 0.188%. Repeatability and reproducibility of whole prostate median pixel ADC both yielded wCVs of 0.033 (N = 29). In 10 subjects with an evaluable focal lesion, the individual reader wCVs were 0.148 and 0.074 (repeatability) and 0.137 and 0.078 (reproducibility). All time points demonstrated good to excellent interreader reliability for focal lesion ADC (ICCV1  = 0.89; ICCV2pre  = 0.76; ICCV2post  = 0.94). DATA CONCLUSION: This study met the QIBA claim for prostate ADC. Test-retest repeatability and multi-day reproducibility were largely equivalent. Interreader reliability for focal lesion ADC was high across time points. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2 TOC CATEGORY: Pelvis.

Systematic Biopsy of the Prostate can Be Omitted in Men with PI-RADS™ 5 and Prostate Specific Antigen Density Greater than 15.

PURPOSE: We evaluated the prostate cancer and clinically significant prostate cancer detection on systematic biopsy (SB), target biopsy (TB) alone and combined SB and TB in men with Prostate Imaging Reporting and Data System™ (PI-RADS™) 5 lesion. MATERIALS AND METHODS: From a prospectively maintained prostate biopsy database, we identified consecutive patients with PI-RADS 5 lesion on multiparametric magnetic resonance imaging. The patients underwent multiparametric magnetic resonance imaging followed by transrectal TB of PI-RADS 5 lesion and 12-core SB. The prostate cancer and clinically significant prostate cancer (Grade Group, GG ≥2) detection on SB, TB and SB+TB were determined for all men and accordingly to prostate specific antigen density. Statistic significant was set a p <0.05. RESULTS: Overall, 112 patients met inclusion criteria. The detection rate of prostate cancer for SB, TB and SB+TB was 89%, 93% and 95%, respectively, and for clinically significant prostate cancer it was 72%, 81% and 85%, respectively. SB added 2% prostate cancer and 4% clinically significant prostate cancer detection to TB. A total of 78 patients had prostate specific antigen density >0.15 ng/ml2, and the detection rate of PCa for SB, TB and SB+TB was 92%, 97% and 97%, respectively, and for clinically significant prostate cancer it was 79%, 91% and 95%, respectively. In this population, if SB was omitted, 0 prostate cancer and only 4% (3) of clinically significant prostate cancer would be missed. The clinically significant prostate cancer detection rate improved with increased prostate specific antigen density for SB (p=0.01), TB (p <0.0001) and combined SB+TB (p=0.002). CONCLUSIONS: In patients with PI-RADS 5 on multiparametric magnetic resonance imaging and prostate specific antigen density >0.15 ng/ml2, SB marginally increases clinically significant prostate cancer detection, but not overall prostate cancer detection in comparison to TB alone. Systematic biopsy did not affect patients' management and can be omitted on this population.

Multiparametric magnetic resonance imaging facilitates reclassification during active surveillance for prostate cancer.

OBJECTIVE: To investigate the utility of multiparametric magnetic resonance imaging (mpMRI) in the reassessment and monitoring of patients on active surveillance (AS) for Grade Group (GG) 1 prostate cancer (PCa). PATIENTS AND METHODS: We identified, from our prospectively maintained institutional review board-approved database, 181 consecutive men enrolled on AS for GG 1 PCa who underwent at least one surveillance mpMRI followed by MRI/prostate biopsy (PBx). A subset analysis was performed among 68 patients who underwent serial (at least two) mpMRI/PBx during AS. Pathological progression (PP) was defined as upgrade to GG ≥2 on follow up biopsy. RESULTS: Baseline MRI was performed in 34 patients (19%). At a median follow-up of 2.2 years for the overall cohort, the PP was 12% (6/49) for Prostate Imaging Reporting and Data System (PI-RADS) 1-2 lesions and 37% (48/129) for the PI-RADS ≥3 lesions. The 2-year PP-free survival rate was 84%. Surveillance prostate-specific antigen density (P < 0.001) and surveillance PI-RADS ≥3 (P = 0.002) were independent predictors of PP on reassessment MRI/PBx. In the serial MRI cohort, the 2-year PP-free survival was 95% for the No-MRI-progression group vs 85% for the MRI-progression group (P = 0.02). MRI progression was significantly higher in the PP (62%) than in the No-PP (31%) group (P = 0.04). If serial MRI were used for PCa surveillance and biopsy were triggered based only on MRI progression, 63% of PBx might be postponed at the cost of missing 12% of GG ≥2 PCa in those with stable MRI. Conversely, this strategy would miss 38% of those with upgrading to GG ≥2 PCa on biopsy. Stable serial mpMRI correlates with no reclassification to GG ≥3 PCa during AS. CONCLUSION: On surveillance mpMRI, PI-RADS ≥3 was associated with increased risk of PCa reclassification. Surveillance biopsy based only on MRI progression may avoid a large number of biopsies at the cost of missing many PCa reclassifications.

MRI predicts prostatic urethral involvement in men undergoing radical prostatectomy: implications for cryo-ablation of localized prostate cancer.

PURPOSE: To determine whether multi-parametric magnetic resonance imaging (mpMRI) can reliably predict proximity of prostate cancer to the prostatic urethra in a contemporary series of men undergoing radical prostatectomy (RP) at two academic centers. METHODS: Clinical characteristics of consecutive men undergoing pre-operative mpMRI prior to RP and whole-mount axial serial step-sectioned pathology examination at two academic centers between Jun 2016 and Oct 2018 were analyzed retrospectively. Every tumor was characterized by its pathologic minimum distance to the prostatic urethral lumen (pMDUL). Only the cancer closest to the urethra represented the prostatic urethral index lesion. The radiologic minimum distance of the index lesion to the prostatic urethral lumen was measured and noted as ≤ 5 mm versus > 5 mm. The sensitivity, specificity, positive and negative predicting values (PPV and NPV) and area under the receivers operating characteristics curve (AUC) were calculated for performance of mpMRI for predicting pMDUL ≤ 5 mm. RESULTS: Of the 163 surgical specimens examined, 112 (69%) exhibited a pMDUL ≤ 5 mm. These men had significantly higher grade group (GG) and advanced pathological and clinical stage. The rates of high PI-RADS score and presence of gross extracapsular extension were also significantly greater for the group with pMDUL ≤ 5 mm. The AUC, sensitivity, specificity, PPV, and NPV were 0.641, 51.8, 76.5, 82.9, and 42.4%, respectively, for mpMRI to predict pMDUL < 5 mm. CONCLUSIONS: Nearly 70% of men undergoing RP present with tumor within 5 mm of the prostatic urethra. These tumors present higher risk characteristics, and mpMRI exhibited moderate performance and high PPV in their pre-operative detection. Physicians performing partial gland ablation should take these results into consideration during treatment selection and planning.

High Intensity Focused Ultrasound Hemigland Ablation for Prostate Cancer: Initial Outcomes of a United States Series.

PURPOSE: We report outcomes of hemigland high intensity focused ultrasound ablation as primary treatment for localized prostate cancer in the United States. MATERIALS AND METHODS: A total of 100 consecutive men underwent hemigland high intensity focused ultrasound (December 2015 to December 2019). Primary end point was treatment failure, defined as Grade Group 2 or greater on followup prostate biopsy, radical treatment, systemic therapy, metastases or prostate cancer specific mortality. IIEF (International Index of Erectile Function), I-PSS (International Prostate Symptom Score) and 90-day complications were reported. RESULTS: At study entry patients had very low (8%), low (20%), intermediate favorable (50%), intermediate unfavorable (17%) and high (5%) risk prostate cancer. Median followup was 20 months. The 2-year survival free from treatment failure, Grade Group 2 or greater recurrence, repeat focal high intensity focused ultrasound and radical treatment was 73%, 76%, 90% and 91%, respectively. Bilateral prostate cancer at diagnosis was the sole predictor for Grade Group 2 or greater recurrence (p=0.03). Of men who underwent posttreatment biopsy (58), 10 had in-field and 8 out-of-field Grade Group 2 or greater positive biopsy. Continence (zero pad) was maintained in 100% of patients. Median IIEF-5 and I-PSS scores before vs after hemigland high intensity focused ultrasound were 22 vs 21 (p=0.99) and 9 vs 6 (p=0.005), respectively. Minor and major complications occurred in 13% and 0% of patients. No patient had rectal fistula or died. CONCLUSIONS: Short-term results of focal high intensity focused ultrasound indicate safety, excellent potency and continence preservation, and adequate short-term prostate cancer control. Radical treatment was avoided in 91% of men at 2 years. Men with bilateral prostate cancer at diagnosis have increased risk for Grade Group 2 or greater recurrence. To our knowledge, this is the initial and largest United States series of focal high intensity focused ultrasound as primary treatment for prostate cancer.

One-Stop MRI and MRI/transrectal ultrasound fusion-guided biopsy: an expedited pathway for prostate cancer diagnosis.

PURPOSE: To assess the feasibility, safety, and outcomes of an expedited One-Stop prostate cancer (PCa) diagnostic pathway. PATIENTS AND METHODS: We identified 370 consecutive patients who underwent multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound fusion prostate biopsy (MRI/TRUS-PBx) from our institutional review board-approved database. Patients were divided according to diagnostic pathway: One-Stop (n = 74), with mpMRI and same-day PBx, or Standard (n = 296), with mpMRI followed by a second visit for PBx. mpMRIs were performed and interpreted according to Prostate Imaging-Reporting and Data System (PI-RADS v2). Grade group ≥ 2 PCa defined clinically significant PCa (csPCa). Statistical significance was considered when p < 0.05. RESULTS: Age (66 vs 66 years, p = 0.59) and PSA density (0.1 vs 0.1 ng/mL2, p = 0.26) were not different between One-Stop vs Standard pathway, respectively. One-Stop patients lived further away from the hospital than Standard patients (163 vs 31 km; p < 0.01), and experienced shorter time from mpMRI to PBx (0 vs 7 days; p < 0.01). The number (p = 0.56) and distribution of PI-RADS lesions (p = 0.67) were not different between the groups. All procedures were completed successfully with similar perioperative complications rate (p = 0.24). For patients with PI-RADS 3-5 lesions, the csPCa detection rate (49% vs 41%, p = 0.55) was similar for One-Stop vs Standard, respectively. The negative predictive value of mpMRI (PI-RADS 1-2) for csPCa was 78% for One-Stop vs 83% for Standard (p = 0.99). On multivariate analysis, age, prostate volume and PI-RADS score (p < 0.01), but not diagnostic pathway, predicted csPCa detection. CONCLUSION: A One-Stop PCa diagnostic pathway is feasible, safe, and provides similar outcomes in a shorter time compared to the Standard two-visit diagnostic pathway.

Vascularized Lymph Node Transfer: A Primer for the Radiologist.

Lymphedema, the accumulation of lymphatic fluid in the tissues, is a chronic disease and a major cause of long-term morbidity and disability. Lymphedema is usually a secondary condition, often caused by prior oncologic therapy, such as surgery for cancers, radiation therapy, and chemotherapy. Treatment for lymphedema has traditionally been conservative and limited, but new surgical and microsurgical procedures have arisen in recent years. Vascularized lymph node transfer (VLNT) is one of the most promising new microsurgeries. VLNT involves the transfer of functional lymph nodes (LNs) from a healthy donor site to an area of the body with damaged or diseased lymphatic drainage. The goal of the transplant is to restore physiologic LN drainage and improve lymphedema. Donor LNs are commonly found in the groin, axilla, neck, omentum, or submental region. Imaging can be used for preoperative planning to identify donor sites with the richest number of LNs. This can help identify those patients who may be candidates for VLNT and can help identify the best anatomic site for surgical harvest in those candidates. Imaging can be performed with US, CT, or MRI. VLNT preoperative imaging often requires acquisition techniques and reconstruction parameters that differ from those used in routine diagnostic imaging. Furthermore, to properly identify target LNs, the radiologist must be aware of surgical anatomic landmarks. Online supplemental material is available for this article. ©RSNA, 2020.

Which Patients with Negative Magnetic Resonance Imaging Can Safely Avoid Biopsy for Prostate Cancer?

PURPOSE: We sought to determine whether there is a subset of men who can avoid prostate biopsy based on multiparametric magnetic resonance imaging and clinical characteristics. MATERIALS AND METHODS: Of 1,149 consecutive men who underwent prostate biopsy from October 2011 to March 2017, 135 had prebiopsy negative multiparametric magnetic resonance imaging with PI-RADS™ (Prostate Imaging Reporting and Data System) score less than 3. The detection rate of clinically significant prostate cancer was evaluated according to prostate specific antigen density and prior biopsy history. Clinically significant prostate cancer was defined as Grade Group 2 or greater. Multivariable logistic regression analysis was performed to identify predictors of nonclinically significant prostate cancer on biopsy. RESULTS: The prostate cancer and clinically significant prostate cancer detection rates were 38% and 18%, respectively. Men with biopsy detected, clinically significant prostate cancer had a smaller prostate (p = 0.004), higher prostate specific antigen density (p = 0.02) and no history of prior negative biopsy (p = 0.01) compared to the nonclinically significant prostate cancer cohort. Prostate specific antigen density less than 0.15 ng/ml/cc (p <0.001) and prior negative biopsy (p = 0.005) were independent predictors of absent clinically significant prostate cancer on biopsy. The negative predictive value of multiparametric magnetic resonance imaging for biopsy detection of clinically significant prostate cancer improved with decreasing prostate specific antigen density, primarily in men with prior negative biopsy (p = 0.001) but not in biopsy naïve men. Of the men 32% had the combination of negative multiparametric magnetic resonance imaging, prostate specific antigen density less than 0.15 ng/ml/cc and negative prior biopsy, and none had clinically significant prostate cancer on repeat biopsy. The incidence of biopsy identified, clinically significant prostate cancer was 18%, 10% and 0% in men with negative multiparametric magnetic resonance imaging only, men with negative multiparametric magnetic resonance imaging and prostate specific antigen density less than 0.15 ng/ml/cc, and men with negative multiparametric magnetic resonance imaging, prostate specific antigen density less than 0.15 ng/ml/cc and negative prior biopsy, respectively. CONCLUSIONS: We propose that a subset of men with negative multiparametric magnetic resonance imaging, prostate specific antigen density less than 0.15 ng/ml/cc and prior negative biopsy may safely avoid rebiopsy. Conversely prostate biopsy should be considered in biopsy naïve men regardless of negative multiparametric magnetic resonance imaging, particularly those with prostate specific antigen density greater than 0.15 ng/ml/cc.

Preoperative Pneumoperitoneum: Low-Risk Surgical Adjunct to the Surgical Management of Dense Abdominal Adhesions.

Surgical lysis of intra-abdominal adhesions is associated with a high rate of complications. This brief report presents 24 patients with dense intra-abdominal adhesions who underwent preoperative progressive pneumoperitoneum (PPP) prior to surgical lysis of adhesions. PPP was successfully performed in 23 patients, with few adverse events, resulting in subjectively improved ease of intraoperative tissue dissection. One patient withdrew due to intractable pain during insufflation. The results suggest that PPP is a low-risk technique with the potential to improve access to intra-abdominal structures in patients for whom conventional surgical therapy is predicted to carry a high rate of complications.

Contrast-Enhanced Transrectal Ultrasound for Follow-up After Focal HIFU Ablation for Prostate Cancer.

The optimal strategy for imaging after focal therapy for prostate cancer is evolving. This series is an initial report on the use of contrast-enhanced transrectal ultrasound (TRUS) in follow-up of patients after high-intensity focused ultrasound (HIFU) hemiablation for prostate cancer. In 7 patients who underwent HIFU hemiablation, contrast-enhanced TRUS findings were as follows: (1) contrast-enhanced TRUS clearly showed the HIFU ablation defect as a sharply marginated nonenhancing zone in all patients; (2) contrast-enhanced TRUS identified suspicious foci of recurrent enhancement within the ablation zone in 2 patients, facilitating image-guided prostate biopsy, which showed prostate cancer; and (3) contrast-enhanced TRUS findings correlated with multiparametric magnetic resonance imaging and biopsy histologic findings.

MRI features of primary rare malignancies of the liver: A report from four university centres.

PURPOSE: To determine if rare primary malignancies of the liver may have consistent features on magnetic resonance imaging (MRI). MATERIALS AND METHODS: This IRB-compliant retrospective study reviewed the records from the pathology departments of four university centres over an 11-year period from 2005-2016 to identify rare primary malignant tumours, which were cross-referenced with MRI records. MRI studies of these patients were reviewed to determine if these tumours exhibited consistent and distinctive features. RESULTS: Sixty patients were identified with rare primary liver tumours. The following distinctive features and frequency of occurrence were observed: mixed hepatocellular carcinoma-cholangiocarcinoma showed regions of wash-out in 7/19 of patients; 6/6 of fibrolamellar carcinomas demonstrated large heterogeneous lesions with large heterogeneous central scars; epithelioid haemangioendothelioma larger than 2 cm showed target-like enhancement in late-phase enhancement in 9/13; sarcomas excluding angiosarcoma had central necrosis in 3/9 and haemorrhage in 5/9; angiosarcomas showed centripedal progressive nodular enhancement in 3/6 and showed regions of haemorrhage in 3/6; and 7/7 of primary hepatic lymphomas showed encasement of vessels. CONCLUSION: Although helpful features for the differentiation of rare primary malignancies of the liver are identified, no MRI features appear to be specific and therefore histopathological confirmation is usually required for definitive diagnosis. KEY POINTS: • No MRI features appear to be specific for rare primary liver malignancies. • Haemorrhage is a helpful sign in diagnosis of primary hepatic sarcomas. • Angiosarcomas may show progressive nodular enhancement towards the centre mimicking haemangioma. • Vessel encasement is a helpful sign in diagnosis of primary hepatic lymphoma.

Morphometric analysis of prostate zonal anatomy using magnetic resonance imaging: impact on age-related changes in patients in Japan and the USA.

OBJECTIVES: To evaluate the impact of morphometric magnetic resonance imaging (MRI) analysis of the prostate zonal anatomy on aging, prostatic hypertrophy and lower urinary tract symptoms in patients from Japan and the USA. SUBJECTS AND METHODS: A retrospective analysis of 307 men, including 156 men from Japan and 151 from the USA, who consecutively underwent 3-Tesla MRI and International Prostate Symptom Score (IPSS) assessment because of elevated PSA levels. Using Synapse-Vincent (Fujifilm), the prostatic zones were segmented in each axial step-section of the T2-weighted MRI to reconstruct a three-dimensional model of the prostate, which was used to calculate: zonal volumes (whole-gland prostate, transition zone and peripheral zone volumes); the presumed circle area ratio (PCAR); and PZ thickness. Bivariate associations were quantified using Spearman's rank correlation coefficients. RESULTS: The USA subgroup had a greater prostate volume (49 vs 42 mL; P = 0.003) and TZ volume (26 vs 20 mL; P < 0.001) than the Japan subgroup, with no difference in PZ volume (19 vs 20 mL; P = 0.2). There was no age-related increase in PZ volume in either of the subgroups or in the entire cohort (P = 0.9, P = 0.2, P = 0.3, respectively). PZ thickness had a significant negative correlation with PCAR (P < 0.001) and TZ volume (P < 0.001). The greater the increase in the TZ volume with the increase in PCAR, which probably correlates with obstructive pressure, the thinner the PZ became. PCAR had a significant positive correlation with IPSS (P = 0.003) and obstructive symptoms (P = 0.007), while PZ thickness had a significant negative correlation (P = 0.018). CONCLUSIONS: No age-related increases and no differences between the Japanese and the US subgroups were found with regard to PZ volume. The more TZ volume increased, the higher the obstructive pressure and the thinner the PZ became; these changes were associated with increased obstructive symptoms. MRI analysis of prostate zonal anatomy enhanced our understanding of age-related changes in morphology and urinary symptoms.

Improving Detection of Iron Deposition in Cirrhotic Liver Using Susceptibility-Weighted Imaging With Emphasis on Histopathological Correlation.

OBJECTIVE: The aim of this study was to investigate the value of susceptibility-weighted imaging (SWI) for detection and quantification of iron deposition in cirrhotic liver. METHODS: Fifty-five cirrhotic patients underwent hepatic magnetic resonance imaging examination including SWI and multiecho T2*-weighted imaging (T2*WI). Detection of iron deposition and number of siderotic nodules were compared between SWI and T2*WI. Correlation among SWI phase value, T2* value, and hepatic iron concentration were determined. RESULTS: Susceptibility-weighted imaging significantly improved detection of iron deposition compared with T2*WI (90.7% vs 66.7%, P = 0.002), attributing to grade 1 (73.3% vs 26.7%, P = 0.027) and grade 2 (93.8% vs 56.3%, P = 0.037). Iron deposition of grade 3 and 4 could be detected by both SWI and T2*WI. The number of siderotic nodules visualized on SWI was significantly larger than that on T2*WI (107.5 ± 7.4 vs 62.7 ± 4.6, P = 0.002). There were significantly negative correlation between phase value and iron score (r = -0.803), and positive correlation between phase value and T2* value (r = 0.771). CONCLUSIONS: Susceptibility-weighted imaging can improve detection of minimal and mild iron deposition in cirrhotic liver.