Immunotherapy for metastatic liver disease from colorectal carcinoma: case series from the Middle East.

Immunotherapy poses new considerations and alterations to the management of metastatic colorectal carcinoma (mCRC), where chemotherapy achieves complete radiological response but yields complete pathological response in few patients only. Immunotherapy may be superior in the conversion of unresectable disease to resectable liver lesions from mCRC and downsizing borderline lesions for more feasible resectability and achieving complete pathologic response, with the potential for cure and to alter current, established guidelines for surgical resection with a shift from chemotherapy. We present two patients with hepatic lesions from mCRC characterized by deficient mismatch repair (dMMR) which were unresectable after traditional chemotherapy but were converted to resectable lesions with a complete histopathological response following immunotherapy. Complete histopathologic response and radiologic regression or disappearance of liver lesions was observed in patients with dMMR mCRC after pembrolizumab. Immunotherapy exhibits notable potential for cure, achieving complete, successful surgical resection and improving prognosis.

Abdominal and pelvic splenosis: atypical findings, pitfalls, and mimics.

Splenosis is an acquired form of ectopic splenic tissue that typically arises after trauma or splenectomy. It is often an incidental image finding in an otherwise asymptomatic patient, but the spectrum of symptoms varies based on the site of implantation. Radiologists should be familiar with the imaging features of splenosis to avoid mistaking it for malignancy. Splenosis has identical imaging features to that of the native spleen on US, CT, MRI, and nuclear medicine examinations. Therefore, when the radiologic findings support the diagnosis of splenosis, the patient can be spared invasive procedures for tissue sampling.

Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings.

BACKGROUND: Recombinant leptin therapy reverses nonalcoholic steatohepatitis (NASH) in leptin-deficient lipodystrophy. We inquired if leptin therapy would improve nonalcoholic steatohepatitis in more common forms of this heterogeneous condition. METHODS: Nine male patients with relative leptin deficiency (level < 25th percentile of body mass index- and gender-matched United States population) and biopsy-proven NASH and 23 patients with partial lipodystrophy and NASH were recruited for two distinctive open-label trials. Participants received leptin therapy in the form of metreleptin for 12 months. The primary endpoints were the global nonalcoholic steatohepatitis scores from paired liver biopsies scored blindly. FINDINGS: Of 9 participants recruited in the relative leptin deficiency treatment study, 7 completed 12-months of therapy. Mean global NASH scores were reduced from 8 ± 3 to 5 ± 2 (range: from 1 to 6, P = 0.004). In the partial lipodystrophy study, 19 of 22 subjects completed 12 months of treatment, and 18 completed a second liver biopsy. Global NASH scores also reduced significantly from 6 ± 2 to 5 ± 2 (range: from -2 to 4, P = 0.008). In both studies, the predominant changes were in steatosis and hepatic injury scores. CONCLUSION: Our findings show that patients with NASH associated with both relative leptin deficiency and partial lipodystrophy have reductions in hepatic steatosis and injury in response to exogenous leptin therapy. Moreover, leptin deficiency may have regulatory effects in mediating fat deposition and ensuing injury in the liver.TRIAL REGISTRATION. ClinicalTrials.gov NCT00596934 and NCT01679197.

Presentation of intestinal malrotation and midgut volvulus in adults: Case report & literature review.

INTRODUCTION: Malrotation is considered a newborn disease. This case report sheds light on the rare, but possible late presentation of malrotation in adulthood, which if missed, can leave the patient in a detrimental state. PRESENTATION OF CASE: 28-year-old female presented in critical state with acute abdomen. Computed tomography abdomen/pelvis showed midgut volvulus, requiring urgent laparotomy. The patient's bowels were discolored, yet they normalized upon detorsion, except for a small portion, which was equivocal and left for observation. Ladd's bands were excised, and the abdomen was closed with Bogota bag for re-exploration. The patient underwent two more laparotomies to observe the intestinal segment until it was back to normal. Ladd procedure was then completed, and an absorbable mesh was applied. Follow-up of 20 months has been uneventful, except for a small, asymptomatic, incisional hernia. DISCUSSION: Malrotation in adults is often missed due to its subacute, nonspecific presentation. It is often diagnosed by CT abdomen, which shows inversion or vertical positioning of the superior mesenteric vessels. Symptomatic, but stable patients, can undergo laparoscopic Ladd procedure, which carries the benefit of less length of stay. While an incidental malrotation can be prophylactically operated on, correcting asymptomatic malrotation beyond age of 20 is ineffective and possibly harmful. CONCLUSION: Intestinal malrotation presenting in an adult should be on the differential diagnosis when dealing with abdominal pain, especially in the context of small bowel obstruction in a virgin abdomen. It is vital to consider a patient's age prior to prophylactically operate on malrotation discovered incidentally.

Management of patients with high-risk and advanced prostate cancer in the Middle East: resource-stratified consensus recommendations.

PURPOSE: Prostate cancer care in the Middle East is highly variable and access to specialist multidisciplinary management is limited. Academic tertiary referral centers offer cutting-edge diagnosis and treatment; however, in many parts of the region, patients are managed by non-specialists with limited resources. Due to many factors including lack of awareness and lack of prostate-specific antigen (PSA) screening, a high percentage of men present with locally advanced and metastatic prostate cancer at diagnosis. The aim of these recommendations is to assist clinicians in managing patients with different levels of access to diagnostic and treatment modalities. METHODS: The first Advanced Prostate Cancer Consensus Conference (APCCC) satellite meeting for the Middle East was held in Beirut, Lebanon, November 2017. During this meeting a consortium of urologists, medical oncologists, radiation oncologist and imaging specialists practicing in Lebanon, Syria, Iraq, Kuwait and Saudi Arabia voted on a selection of consensus questions. An additional workshop to formulate resource-stratified consensus recommendations was held in March 2019. RESULTS: Variations in practice based on available resources have been proposed to form resource-stratified recommendations for imaging at diagnosis, initial management of localized prostate cancer requiring therapy, treatment of castration-sensitive/naïve advanced prostate cancer and treatment of castration-resistant prostate cancer. CONCLUSION: This is the first regional consensus on prostate cancer management from the Middle East. The following recommendations will be useful to urologists and oncologists practicing in all areas with limited access to specialist multi-disciplinary teams, diagnostic modalities and treatment resources.

MRI evaluation of the placenta from normal variants to abnormalities of implantation and malignancies.

Even though the placenta has been known for millennia, it is still considered one of the most complex and least understood human organs. Imaging of the placenta is gaining attention due to its impact on fetal and maternal outcomes. MRI plays a vital role in evaluation of inconclusive cases by ultrasonography. It enables precise mapping of placental abnormalities for proper multidisciplinary planning and management. In this article we provide a comprehensive in-depth review of the role of antenatal MR in evaluating "The Placenta." We will describe the protocols and techniques used for MRI of the placenta, review anatomy of the placenta, describe MRI features of major placental abnormalities including those related to position, depth of implantation, hemorrhage, gestational trophoblastic neoplasia, and retained products of conception and discuss the added value of MRI in the management and preoperative planning of such abnormalities. Level of Evidence: 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:1702-1717.

Diagnostic accuracy of MRI with extracellular vs. hepatobiliary contrast material for detection of residual hepatocellular carcinoma after locoregional treatment.

PURPOSE: To compare the diagnostic accuracy of extracellular gadolinium-based contrast-enhanced MRI (Gd-MRI) and gadoxetic acid-enhanced MRI (EOB-MRI) for the assessment of hepatocellular carcinoma (HCC) response to locoregional therapy (LRT) using explant correlation as the reference standard. METHODS: Forty-nine subjects with cirrhosis and HCC treated with LRT who underwent liver MRI using either Gd-MRI (n = 26) or EOB-MRI (n = 23) within 90 days of liver transplantation were included. Four radiologists reviewed the MR images blinded to histology to determine the size and percentage of viable residual HCC using a per-lesion explant reference standard. Sensitivities, specificities, accuracies, and agreement with histology for the detection residual HCC were calculated. RESULTS: Gd-MRI had greater agreement with histology (ICC: 0.98 [0.95-0.99] vs. 0.80 [0.63-0.90]) and greater sensitivity for viable HCC (76% [13/17 50-93%] vs. 58% [7/12; 28-85%]) than EOB-MRI; specificities were similar (84% [16/19; 60-97%] vs. 85% [23/27; 66-96%]). Areas under ROC curves for detecting residual viable tumor were 0.80 (0.64-0.92) for Gd-MRI and 0.72 (0.55-0.85) for EOB-MRI. Gd-MRI had greater inter-rater agreement than EOB-MRI for determining the size of residual viable HCC (ICC: 0.96 [0.92-0.98] vs. 0.85 [0.72-0.92]). CONCLUSION: Gd-MRI may be more accurate and precise than EOB-MRI for the assessment of viable HCC following LRT.

Iron-Containing Abdominal Pathologies: Exploiting Magnetic Susceptibility Artifact on Dual-Echo Gradient-Echo Magnetic Resonance Imaging.

A multitude of pathologic entities involve abnormal iron deposition in the abdomen. These lesions demonstrate decreased signal on longer magnetic resonance sequences with longer echo time due to T2* effect. Dual-echo gradient-echo sequences demonstrate increased susceptibility artifact with longer echo sequences. In this article, the spectrum of iron-containing abdominal pathologies is illustrated, with their characteristic distributions. Included is a brief discussion of the physics of magnetic resonance imaging of iron-containing lesions.

Evidence Supporting LI-RADS Major Features for CT- and MR Imaging-based Diagnosis of Hepatocellular Carcinoma: A Systematic Review.

The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting relative probability of HCC to imaging-detected liver observations based on major and ancillary imaging features. LI-RADS also includes imaging features suggesting malignancy other than HCC. Supported and endorsed by the American College of Radiology (ACR), the system has been developed by a committee of radiologists, hepatologists, pathologists, surgeons, lexicon experts, and ACR staff, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Development of LI-RADS has been based on literature review, expert opinion, rounds of testing and iteration, and feedback from users. This article summarizes and assesses the quality of evidence supporting each LI-RADS major feature for diagnosis of HCC, as well as of the LI-RADS imaging features suggesting malignancy other than HCC. Based on the evidence, recommendations are provided for or against their continued inclusion in LI-RADS. © RSNA, 2017 Online supplemental material is available for this article.

Interreader Reliability of LI-RADS Version 2014 Algorithm and Imaging Features for Diagnosis of Hepatocellular Carcinoma: A Large International Multireader Study.

Purpose To determine in a large multicenter multireader setting the interreader reliability of Liver Imaging Reporting and Data System (LI-RADS) version 2014 categories, the major imaging features seen with computed tomography (CT) and magnetic resonance (MR) imaging, and the potential effect of reader demographics on agreement with a preselected nonconsecutive image set. Materials and Methods Institutional review board approval was obtained, and patient consent was waived for this retrospective study. Ten image sets, comprising 38-40 unique studies (equal number of CT and MR imaging studies, uniformly distributed LI-RADS categories), were randomly allocated to readers. Images were acquired in unenhanced and standard contrast material-enhanced phases, with observation diameter and growth data provided. Readers completed a demographic survey, assigned LI-RADS version 2014 categories, and assessed major features. Intraclass correlation coefficient (ICC) assessed with mixed-model regression analyses was the metric for interreader reliability of assigning categories and major features. Results A total of 113 readers evaluated 380 image sets. ICC of final LI-RADS category assignment was 0.67 (95% confidence interval [CI]: 0.61, 0.71) for CT and 0.73 (95% CI: 0.68, 0.77) for MR imaging. ICC was 0.87 (95% CI: 0.84, 0.90) for arterial phase hyperenhancement, 0.85 (95% CI: 0.81, 0.88) for washout appearance, and 0.84 (95% CI: 0.80, 0.87) for capsule appearance. ICC was not significantly affected by liver expertise, LI-RADS familiarity, or years of postresidency practice (ICC range, 0.69-0.70; ICC difference, 0.003-0.01 [95% CI: -0.003 to -0.01, 0.004-0.02]. ICC was borderline higher for private practice readers than for academic readers (ICC difference, 0.009; 95% CI: 0.000, 0.021). Conclusion ICC is good for final LI-RADS categorization and high for major feature characterization, with minimal reader demographic effect. Of note, our results using selected image sets from nonconsecutive examinations are not necessarily comparable with those of prior studies that used consecutive examination series. © RSNA, 2017.

Imaging Findings Within the First 12 Months of Hepatocellular Carcinoma Treated With Stereotactic Body Radiation Therapy.

PURPOSE: To correlate the imaging findings of treated hepatocellular carcinoma (HCC) after stereotactic body radiation therapy (SBRT) with explant pathology and alpha-fetoprotein (AFP) response. METHODS AND MATERIALS: From 2007 to 2015, of 146 patients treated with liver SBRT for Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma, 10 were identified with inclusion criteria and had regular interval follow-up magnetic resonance imaging/triple phase computed tomography and explant pathology or declining AFP values for radiology-pathology response correlation. Reference standards for successful response were >90% necrosis on explant pathology or pretreatment AFP >75 ng/mL normalizing to <10 ng/mL within 1 year after SBRT without other treatment. Subjects were treated with 24 to 50 Gy in 3 to 5 fractions. Multiphasic magnetic resonance imaging or computed tomography performed at 3, 6, 9, and 12 months after SBRT was compared with pretreatment imaging by 2 expert radiologists. Descriptive statistics were calculated. RESULTS: There were 10 subjects with 10 treated HCCs, classified as 3 Organ Procurement and Transplantation Network (OPTN) 5a, 4 OPTN 5b, and 3 OPTN 5x. All had successfully treated HCCs, according to explant pathology or declining AFP. Four of 10 HCCs had persistent central arterial hyperenhancement 3 to 12 months after SBRT; persistent wash-out was common up to 12 months (9 of 10). Of 10 treated HCCs, 9 exhibited decreased size at 12 months. Liver parenchyma adjacent to the lesion showed early (3-6 months) hyperemia followed by late (6-12 months) capsular retraction and delayed enhancement. No patient had a significant decline in liver function. CONCLUSIONS: In the absence of increasing size, persistent central arterial hyperenhancement and wash-out can occur within the first 12 months after SBRT in successfully treated HCCs and may not represent residual viable tumor. Liver parenchyma adjacent to the treated lesion showed inflammation followed by fibrosis, without significant change in hepatic function. Until a radiologic signature of tumor control is determined, freedom from local progression seems to be the best measure of HCC control after SBRT.

Reinterpretation of Outside Hospital MRI Abdomen Examinations in Patients With Cirrhosis: Is the OPTN Mandate Necessary?

OBJECTIVE: The objective of our study was to determine the relevance of a policy mandating reinterpretation of outside abdominal MRI examinations in patients with cirrhosis at risk for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A random subset (n = 125) of consecutive outside-hospital MRI abdomen examinations (n = 473) performed in subjects with cirrhosis and reinterpreted at a tertiary care center by one of 11 fellowship-trained radiologists was included. The original and reinterpreted reports were compared in consensus by two hepatobiliary imaging experts; one hepatologist determined the clinical impact. Each was blinded to outcome. The primary outcome was discrepancies relevant to the Organ Procurement and Transplantation Network (OPTN), including diagnosis of HCC and exceeding the Milan criteria for transplantation. Rates were compared with the McNemar test. RESULTS: HCC was diagnosed in 34% (43/125) of reinterpretations; of these, 44% (19/43) were concordant, 42% (18/43) originally were considered suspicious but not diagnostic of HCC, and 14% (6/43) were discordant. The Milan criteria were exceeded in 21% (26/125) of reinterpretations; of these, 73% (19/26) were concordant and 27% (7/26) were discordant. Overall, 10% (12/125) of subjects had a discrepant diagnosis of HCC, and 10% (12/125) of subjects had discrepant Milan status; 26% (11/43) of masses diagnosed to be HCC had been biopsied at the original institution. Original reports were significantly more likely to be missing major details (26% [32/125] vs 0.8% [1/125], p < 0.001) or difficult to understand (18% [23/125] vs 0.8% [1/125], p < 0.001). Predicted clinical management differed in 50% (62/125) of reinterpretations. CONCLUSION: The OPTN mandate for expert interpretation of liver MRI in patients with cirrhosis appears justified.

Imaging in Patients with Cirrhosis: Current Evidence.

There have been major changes in the management and reporting of hepatocellular carcinoma (HCC) in the last decade. Cross-sectional imaging is now pivotal in the management of cirrhotic patients, in particular in the diagnosis and staging of HCC. Although diagnostic systems have become relatively well developed, approximately one-third of HCC nodules may have an atypical appearance, necessitating ancillary testing, close follow-up, or biopsy. The introduction of standardized diagnostic and reporting systems has improved communication between radiologists and clinicians, but there remains substantial disagreement between radiologists in feature assignment and nodule characterization.

Predicting the likelihood of a persistent bile duct stone in patients with suspected choledocholithiasis: accuracy of existing guidelines and the impact of laboratory trends.

BACKGROUND: Existing guidelines aim to stratify the likelihood of choledocholithiasis to guide the use of ERCP versus a lower-risk diagnostic study such as EUS, MRCP, or intraoperative cholangiography. OBJECTIVE: To assess the performance of existing guidelines in predicting choledocholithiasis and to determine whether trends in laboratory parameters improve diagnostic accuracy. DESIGN: Retrospective cohort study. SETTING: Tertiary-care hospital. PATIENTS: Hospitalized patients presenting with suspected choledocholithiasis over a 6-year period. INTERVENTIONS: Assessment of the American Society for Gastrointestinal Endoscopy (ASGE) guidelines, its component variables, and laboratory trends in predicting choledocholithiasis. MAIN OUTCOME MEASUREMENTS: The presence of choledocholithiasis confirmed by EUS, MRCP, or ERCP. RESULTS: A total of 179 (35.9%) of the 498 eligible patients met ASGE high-probability criteria for choledocholithiasis on initial presentation. Of those, 99 patients (56.3%) had a stone/sludge on subsequent confirmatory test. Of patients not meeting high-probability criteria on presentation, 111 (34.8%) had a stone/sludge. The overall accuracy of the guidelines in detecting choledocholithiasis was 62.1% (47.4% sensitivity, 73% specificity) based on data available at presentation. The accuracy was unchanged when incorporating the second set of liver chemistries obtained after admission (63.2%), suggesting that laboratory trends do not improve performance. LIMITATIONS: Retrospective study, inconsistent timing of the second set of biochemical markers. CONCLUSION: In our cohort of patients, existing choledocholithiasis guidelines lacked diagnostic accuracy, likely resulting in overuse of ERCP. Incorporation of laboratory trends did not improve performance. Additional research focused on risk stratification is necessary to meet the goal of eliminating unnecessary diagnostic ERCP.

Functional and anatomical differences between continent and incontinent men post radical prostatectomy on urodynamics and 3T MRI: a pilot study.

AIMS: There are competing hypotheses about the etiology of post prostatectomy incontinence (PPI). The purpose of this study was to determine the anatomical and functional differences between men with and without PPI. METHODS: Case-control study of continent and incontinent men after radical prostatectomy who underwent functional and anatomic studies with urodynamics and 3.0 Tesla MRI. All men were at least 12 months post prostatectomy and none had a history of pelvic radiation or any prior surgery for incontinence. RESULTS: Baseline demographics, surgical approach, and pathology were similar between incontinent (cases) (n = 14) and continent (controls) (n = 12) men. Among the cases, the average 24 hr pad weight was 400.0 ± 176.9 g with a mean of 2.4 ± 0.7 pads per day. Urethral pressure profiles at rest did not significantly differ between groups; however, with a Kegel maneuver the rise in urethral pressure was 2.6 fold higher in controls. On MRI, the urethral length was 31-35% shorter and the bladder neck was 28.9° more funneled in cases. There were no differences in levator ani muscle size between groups. There was distortion of the sphincter area in 85.7% of cases and in 16.7% of controls (P = 0.001). CONCLUSIONS: Men with PPI were not able to increase urethral pressure with a Kegel maneuver despite similar resting urethral pressure profiles. Additionally, incontinent men had shorter urethras and were more likely to have distortion of the sphincter area. All suggesting that the sphincter in men with PPI is both diminutive and poorly functional.

A pilot study of diffusion-weighted MRI in patients undergoing neoadjuvant chemoradiation for pancreatic cancer.

PURPOSE: In the current study we examined the ability of diffusion MRI (dMRI) to predict pathologic response in pancreatic cancer patients receiving neoadjuvant chemoradiation. METHODS: We performed a prospective pilot study of dMRI in patients with resectable pancreatic cancer. Patients underwent dMRI prior to neoadjuvant chemoradiation. Surgical specimens were graded according to the percent tumor cell destruction. Apparent diffusion coefficient (ADC) maps were used to generate whole-tumor derived ADC histogram distributions and mean ADC values. The primary objective of the study was to correlate ADC parameters with pathologic and CT response. RESULTS: Ten of the 12 patients enrolled on the study completed chemoradiation and had surgery. Three were found to be unresectable at the time of surgery and no specimen was obtained. Out of the 7 patients who underwent pancreaticoduodenectomy, 3 had a grade III histopathologic response (> 90% tumor cell destruction), 2 had a grade IIB response (51% to 90% tumor cell destruction), 1 had a grade IIA response (11% to 50% tumor cell destruction), and 1 had a grade I response (> 90% viable tumor). Median survival for patients with a grade III response, grade I-II response, and unresectable disease were 25.6, 18.7, and 6.1 months, respectively. There was a significant correlation between pre-treatment mean tumor ADC values and the amount of tumor cell destruction after chemoradiation with a Pearson correlation coefficient of 0.94 (P = .001). Mean pre-treatment ADC was 161 × 10(- 5) mm(2)/s (n = 3) in responding patients (> 90% tumor cell destruction) compared to 125 × 10(- 5) mm(2)/s (n = 4) in non-responding patients (> 10% viable tumor). CT imaging showed no significant change in tumor size in responders or non-responders. CONCLUSIONS: dMRI may be useful to predict response to chemoradiation in pancreatic cancer. In our study, tumors with a low ADC mean value at baseline responded poorly to standard chemoradiation and would be candidates for intensified therapy.

Imaging techniques for the diagnosis of hepatocellular carcinoma and the evaluation of response to treatment.

Imaging plays a critical role in the diagnosis of hepatocellular carcinoma (HCC). In the USA, non-invasive imaging based diagnosis of HCC has largely replaced biopsy because of the high specificity and positive predictive value of imaging features for HCC. Because of the important role of imaging and the need to promote standardization of the management of HCC, several imaging-based algorithms for the diagnosis of HCC in at-risk patients have been developed.Imaging also plays a vital role in the assessment of HCC response to locoregional therapies (LRT) such as ablative and endovascular therapies. Standard imaging response criteria of solid tumors that rely solely on change in tumor size for determination of therapeutic success are not applicable to HCC undergoing LRT. Therefore, several systems have been developed over the years to objectively evaluate HCC response to LRT.In this review, we will describe major and ancillary imaging features of HCC, how these features are incorporated into the various imaging based algorithms, discuss the differences between algorithms, and address the emerging role of new imaging techniques and contrast agents in the diagnosis of HCC. We will also discuss the importance of assessment of HCC response to LRT, describe patterns of imaging response to the various therapies including newer volumetric and functional response measures, and examine and compare proposed response criteria of HCC to LRT.