Tacrolimus's Time Below Therapeutic Range Is Associated With Acute Pancreatic Graft Rejection and the Development of De Novo Donor-specific Antibodies.

Tacrolimus is pivotal in pancreas transplants but poses challenges in maintaining optimal levels due to recipient differences. This study aimed to explore the utility of time spent below the therapeutic range and intrapatient variability in predicting rejection and de novo donor-specific antibody (dnDSA) development in pancreas graft recipients. This retrospective unicentric study included adult pancreas transplant recipients between January 2006 and July 2020. Recorded variables included demographics, immunosuppression details, HLA matching, biopsy results, dnDSA development, and clinical parameters. Statistical analysis included ROC curves, sensitivity, specificity, and predictive values. A total of 131 patients were included. Those with biopsy-proven acute rejection (BPAR, 12.2%) had more time (39.9% ± 24% vs. 25.72% ± 21.57%, p = 0.016) and tests (41.95% ± 13.57% vs. 29.96% ± 17.33%, p = 0.009) below therapeutic range. Specific cutoffs of 31.5% for time and 34% for tests below the therapeutic range showed a high negative predictive value for BPAR (93.98% and 93.1%, respectively). Similarly, patients with more than 34% of tests below the therapeutic range were associated with dnDSA appearance (38.9% vs. 9.4%, p = 0.012; OR 6.135, 1.346-27.78). In pancreas transplantation, maintaining optimal tacrolimus levels is crucial. Suboptimal test percentages below the therapeutic range prove valuable in identifying acute graft rejection risk.

MRI Using Gadoxetic Acid in the Work-Up of Liver Nodules Not Conclusively Benign in Budd-Chiari Syndrome: A Prospective Long-Term Follow-Up.

Introduction: The incidence of hepatocellular carcinoma (HCC) in Budd-Chiari syndrome (BCS) is unknown and there is no validated diagnostic work-up to define the liver nodules with arterial phase hyperenhancement (APHE), suggesting malignancy. This prospective study evaluates HCC incidence in a Western cohort of patients with BCS and assesses the performance of MRI with hepatobiliary contrast (HB-MRI) for nodule characterization. Methods: Patients with BCS followed in our hospital were prospectively evaluated by MRI with extracellular contrast (EC-MRI). Nodules with APHE categorized as non-conclusively benign by 2 radiologists were studied by HB-MRI and reviewed by 2 radiologists blinded to the EC-MRI results. A new EC-MRI 1 year later and clinical, analytical, and sonographic follow-up every 6 months for a median of 10 years was performed. Results: A total of 55 non-conclusively benign nodules with APHE were detected at EC-MRI in 41 patients. While 32 of them were suggestive of HCC by EC-MRI, all the 55 nodules showed increased uptake of hepatobiliary contrast. An unequivocal central scar was seen in 12/55 nodules at HB-MRI regardless of it was not detected on the EC-MRI. None of the nodules was hypointense in the hepatobiliary phase (HBP). HCC was not detected during a median of 10 years of follow-up. Conclusions: Detection of nodules with APHE is frequent in patients with BCS, but HCC is rare in Western patients with BCS. While EC-MRI may detect nodules suggesting malignancy, the identification of contrast uptake in the HBP at HB-MRI may help categorize them as benign.

Validation of the Back-table Graft Arterial Anastomosis between the Splenic Artery and Superior Mesenteric Artery: Arterial Complications after a 21-year Single-center Experience of Pancreas Transplantation.

OBJECTIVE: To determine the role of the arterial splenomesenteric anastomosis (ASMA) vascular reconstruction technique in terms of arterial vascular complications in pancreas transplant (PT) recipients. SUMMARY BACKGROUND DATA: The ASMA technique was first described in 1992 by Hospital Clínic Barcelona group. Regardless that the iliac Y-graft technique is the most frequently used worldwide, evidence of arterial complications and implications of using a different back-table reconstruction is conspicuously absent in the literature. METHODS: Descriptive review of 407 PTs performed at a single center (1999-2019) by analyzing the type of arterial reconstruction technique, focusing on ASMA. The endpoints were the management of arterial complications and long-term patient and graft survival. RESULTS: ASMA was performed in 376 cases (92.4%) and a Y-graft in 31 cases (7.6%). A total of 34 arterial complications (8.3%) were diagnosed. In the ASMA group (n=30, 7.9%) they comprised: 15 acute thrombosis; 4 stenosis; 1 pseudoaneurysm and 10 diverse chronic arterial complications while in the Y-graft group (n=4, 12.9%) 3 acute thrombosis and 1 chronic artery-duodenal fistula occurred. Graft salvage was achieved in 16 patients (53.3%) from the ASMA group and in 2 (50%) from the Y-graft. After a median follow-up of 129.2 (IQR 25-75%, 77.2 -182) months the overall graft and patient survival for the whole cohort at 1, 5, and 10 years was 86.7%, 79.5%, 70.5%, and 98.5%, 95.3%, 92.5%, respectively. CONCLUSIONS: The ASMA proves to be a safe and more easily reproducible technique and should therefore be considered for first-line back-table reconstruction in the PT population.

Risk of Treatment Failure and Death after Ablation in Hepatocellular Carcinoma Patients-A Multiparametric Prediction.

BACKGROUND: Ablation is a first-line treatment for Barcelona Clinic Liver Cancer (BCLC)-0/A hepatocellular carcinoma (HCC). However, there are scarce data about patients' outcomes after recurrence. The present study evaluates the impact of patient and tumor characteristics at baseline and at recurrence on the Clinical Decision-Making process. METHODS: We evaluated BCLC-0/A patients treated with percutaneous ablation from January 2010 to November 2018. Clinical and radiological data such as age, tumor location at ablation, pattern of recurrence/progression, and comorbidities during follow-up were registered. Tumor location was divided into 'suboptimal' vs. 'optimal' locations for ablation. The Clinical Decision-Making was based on tumor burden, liver dysfunction, or comorbidities. The statistical analysis included the time-to-recurrence/progression, censoring at time of death, date of last follow-up or liver transplantation, and time-to-event was estimated by the Kaplan-Meier method and Cox regression models to evaluate the risk of an event of death and change of treatment strategy. RESULTS: A total of 225 patients [39.1% BCLC-0 and 60.9% BCLC-A] were included, 190 had unifocal HCC and 82.6% were ≤3 cm. The complete response rate and median overall survival were 96% and 60.7 months. The HCC nodules number (Hazard Ratio-HR 3.1), Child-Pugh (HR 2.4), and Albumin-Bilirubin score (HR 3.2) were associated with increased risk of death during follow-up. HCC in 'suboptimal location' presented a shorter time to recurrence. When comorbidities prevented further loco-regional or systemic treatment, the risk of death was significantly increased (HR 2.0, p = 0.0369) in comparison to those who received treatment. CONCLUSIONS: These results expose the impact of non-liver comorbidities when considering treatment for recurrence after ablation in the real-world setting and in research trials. Ultimately, we identified an orphan population for which effective interventions are needed.

Liver Transplantation for Porto-sinusoidal Vascular Liver Disorder: Long-term Outcome.

BACKGROUND: Porto-sinusoidal vascular liver disorder (PSVD) is a rare disease that occasionally requires liver transplantation (LT), despite usually presenting preserved liver function. There remains a paucity of data pertaining to LT in PSVD. The aim was to identify features associated with post-LT outcomes in PSVD. METHODS: Retrospective multicentre study of 79 patients who received LT for PSVD. RESULTS: Median post-LT follow-up was 37 (range 1-261) mo. Refractory ascites 24 (30%), hepatic encephalopathy 16 (20%), and hepatopulmonary syndrome 13 (16.3%) were the most frequent indications for LT. Hepatocellular carcinoma was the indication in only 2 patients. Twenty-four patients died, 7 due to liver and 17 to non-liver related causes. Post-LT survival was 82.2%, 80.7%, and 68.6% at 1, 2, and 5 y, respectively. Post-LT survival was significantly better in patients without (n = 58) than in those with a persistent severe PSVD-associated condition (n = 21). Pre-LT hyperbilirubinemia levels and creatinine >100 µmol/L were also independently associated with poor survival. Six patients (7.6%) required a second LT. Recurrence of PSVD was confirmed by liver biopsy in only 1 patient and in 3 further patients it was likely. CONCLUSIONS: LT in PSVD is associated with an acceptable outcome in the absence of associated severe conditions. However, persistence of a severe associated condition, pre-LT high bilirubin levels, or creatinine >100 µmol/L impact outcome, and these are features that should be considered when evaluating PSVD patients for LT. PSVD recurrence is possible after LT and needs to be explored, at least, in cases of posttransplant portal hypertension.

A Phase I-II multicenter trial with Avelumab plus autologous dendritic cell vaccine in pre-treated mismatch repair-proficient (MSS) metastatic colorectal cancer patients; GEMCAD 1602 study.

BACKGROUND: Immune check-point blockade (ICB) has shown clinical benefit in mismatch repair-deficient/microsatellite instability high metastatic colorectal cancer (mCRC) but not in mismatch repair-proficient/microsatellite stable patients. Cancer vaccines with autologous dendritic cells (ADC) could be a complementary therapeutic approach to ICB as this combination has the potential to achieve synergistic effects. METHODS: This was a Phase I/II multicentric study with translational sub-studies, to evaluate the safety, pharmacodynamics and anti-tumor effects of Avelumab plus ADC vaccine in heavily pre-treated MSS mCRC patients. Primary objective was to determine the maximum tolerated dose and the efficacy of the combination. The primary end-point was 40% progression-free survival at 6 months with a 2 Simon Stage. RESULTS: A total of 28 patients were screened and 19 pts were included. Combined therapy was safe and well tolerated. An interim analysis (Simon design first-stage) recommended early termination because only 2/19 (11%) patients were disease free at 6 months. Median PFS was 3.1 months [2.1-5.3 months] and overall survival was 12.2 months [3.2-23.2 months]. Stimulation of immune system was observed in vitro but not clinically. The evaluation of basal RNA-seq noted significant changes between pre and post-therapy liver biopsies related to lipid metabolism and transport, inflammation and oxidative stress pathways. CONCLUSIONS: The combination of Avelumab plus ADC vaccine is safe and well tolerated but exhibited modest clinical activity. Our study describes, for the first-time, a de novo post-therapy metabolic rewiring, that could represent novel immunotherapy-induced tumor vulnerabilities.

Immune Profiling of Peripheral Blood Mononuclear Cells at Pancreas Acute Rejection Episodes in Kidney-Pancreas Transplant Recipients.

Profiling of circulating immune cells provides valuable insight to the pathophysiology of acute rejection in organ transplantation. Herein we characterized the peripheral blood mononuclear cells in simultaneous kidney-pancreas transplant recipients. We conducted a retrospective analysis in a biopsy-matched cohort (n = 67) and compared patients with biopsy proven acute rejection (BPAR; 41%) to those without rejection (No-AR). We observed that CD3+ T cells, both CD8+ and CD4+, as well as CD19+ B cells were increased in patients with BPAR, particularly in biopsies performed in the early post-transplant period (<3 months). During this period immune subsets presented a good discriminative ability (CD4+ AUC 0.79; CD8+ AUC 0.80; B cells AUC 0.86; p < 0.05) and outperformed lipase (AUC 0.62; p = 0.12) for the diagnosis of acute rejection. We further evaluated whether this could be explained by differences in frequencies prior to transplantation. Patients presenting with early post-transplant rejection (<3 months) had a significant increase in T-cell frequencies pre-transplant, both CD4+ T cells and CD8+ T cells (p < 0.01), which were associated with a significant inferior rejection-free graft survival. T cell frequencies in peripheral blood correlated with pancreas acute rejection episodes, and variations prior to transplantation were associated with pancreas early acute rejection.

Portal hypertension may influence the registration of hypointensity of small hepatocellular carcinoma in the hepatobiliary phase in gadoxetic acid MR.

BACKGROUND: The aim of the study was to analyze the association between the liver uptake of Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) in the hepatobiliary phase (HBP) in cirrhotic patients and the presence of clinically significant portal hypertension (CSPH), and how these features impact on hepatocellular carcinoma (HCC) detection in the HBP. PATIENTS AND METHODS: Post-hoc analysis of a prospective cohort of 62 cirrhotic patients with newly US-detected nodule between 1-2 cm (study group). Twenty healthy subjects were used as control group. Qualitative and quantitative analysis of the liver contrast uptake in the HBP assessed by Relative Liver-Enhancement (RLE), Liver-Spleen (LSCR), Liver-Muscle (LMCR), and Liver-Kidney Contrast-Ratio (LKCR), Contrast Enhancement Index (CEI), and Hepatic Uptake (HUI), and biliary excretion, were registered. CSPH was confirmed invasively (HVPG > 10 mmHg) or by indirect parameters. The appearance of HCC at the HBP was analyzed. RESULTS: Nineteen patients (30.6%) did not have CSPH. In 41 patients (66.1%) the final diagnosis was HCC. All indices were significantly higher in the control group, indicating a more intense HBP liver signal intensity compared to patients with cirrhosis, even if the comparison was restricted to patients with no CSPH. CSPH was associated to a lower rate of HCC hypointensity in the HBP (51.9% vs. 85.7% without CSPH, p = 0.004). CONCLUSIONS: Liver uptake of Gd-EOB-DTPA at the HBP is decreased in cirrhosis even if the liver function is minimally impaired and it falls down significantly in patients with CSPH compromising the recognition of hypointense lesions. This fact may represent a limitation for the detection of small HCC in patients with cirrhosis and CSPH.

Patient Experience in Pancreas-Kidney Transplantation-A Methodological Approach Towards Innovation in an Established Program.

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components.

Liver cancer risk after HCV cure in patients with advanced liver disease without non-characterized nodules.

BACKGROUND & AIMS: Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population. METHODS: We performed a prospective study including HCV-infected patients with F3/F4 fibrosis, without a history of HCC, and who achieved SVR after DAAs. Patients were only included if they had undergone ultrasound imaging that excluded the presence of HCC/NCLN within 30 days after SVR. All patients were evaluated every 6 months until developing primary liver cancer, death or withdrawal of informed consent. HCC incidence was expressed per 100 patient-years (/100PY). Adherence to screening program was calculated every 6 months for the first 48 months. RESULTS: A total of 185 patients (63/122, F3/F4) were included. Among those with cirrhosis, 92% were Child-Pugh A and 42.7% had clinically significant portal hypertension (CSPH). Albumin-bilirubin score was 1 in 84.9% and 2 in 15.1% of patients, respectively. The median clinical and radiologic follow-up was 52.4 months and 48 months, respectively. Ten patients developed HCC: HCC incidence was 1.46/100PY (95% CI 0.79-2.71) in the whole cohort, 2.24/100PY (95% CI 1.21-4.17) in F4 only and 3.63/100PY (95% CI 1.95-6.74) in patients with CSPH. No HCC was registered in patients with F3. Median time between SVR and HCC occurrence was 28.1 months; 12 non-primary liver cancers were also identified. CONCLUSIONS: Patients with cirrhosis without NCLN at SVR remain at risk of HCC development. The absence of HCC in patients with F3 reinforces their marginal cancer risk, but prospective studies are needed to exclude them from screening programs. LAY SUMMARY: Patients with HCV-related cirrhosis, without non-characterized liver nodules at sustained virologic response, remain at risk of hepatocellular carcinoma despite viral cure. However, the cancer risk after successful direct-acting antiviral treatment is marginal in patients with F3 fibrosis without non-characterized liver nodules. If confirmed in larger prospective studies, current screening recommendations may need to be revisited in this group of patients.

BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update.

There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.

Predicting portal thrombosis in cirrhosis: A prospective study of clinical, ultrasonographic and hemostatic factors.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a relatively frequent event in patients with cirrhosis. While different risk factors for PVT have been reported, such as decreased portal blood flow velocity (PBFV) and parameters related with severity of portal hypertension, these are based on retrospective studies assessing only a discrete number of parameters. The aim of the current study was to evaluate the incidence and risks factors for non-tumoral PVT development in a large prospective cohort of patients with cirrhosis. METHODS: We performed an exhaustive evaluation of clinical, biochemical, inflammatory and acquired/hereditary hemostatic profiles in 369 patients with cirrhosis without PVT who were prospectively followed-up. Doppler ultrasound was performed at baseline and every 6 months or whenever clinically indicated. PVT development was always confirmed by computed tomography. RESULTS: Twenty-nine patients developed non-tumoral PVT, with an incidence of 1.6%, 6% and 8.4% at 1, 3 and 5 years, respectively. Low platelet count, PBFV <15 cm/sec and history of variceal bleeding were factors independently associated with a high PVT risk. No relationship between PVT development and any other clinical biochemical, inflammatory and acquired or hereditary hemostatic parameter was found. CONCLUSIONS: In patients with cirrhosis, the factors predictive of PVT development were mainly those related to the severity of portal hypertension. Our results do not support the role of hemostatic alterations (inherited or acquired) and inflammatory markers in the prediction of PVT in patients with cirrhosis. LAY SUMMARY: Patients with cirrhosis and more severe portal hypertension are at higher risk of non-tumoral portal vein thrombosis development. Acquired or inherited hemostatic disorders, as well as inflammatory status, do not seem to predict the development of portal vein thrombosis in patients with cirrhosis.

Risk of non-tumoural portal vein thrombosis in patients with HCV-induced cirrhosis after sustained virological response.

BACKGROUND & AIMS: Sustained virological response (SVR) to direct-acting antivirals ameliorates portal hypertension, improves hepatic function and may reverse the procoagulant state observed in patients with cirrhosis. However, an unexpected incidence of portal vein thrombosis (PVT) immediately after antiviral therapy has recently been reported. Therefore, we analysed the long-term impact of SVR on the development of non-tumoural PVT. METHODS: Our study comprised of two well-characterized prospective cohorts (hepatitis C virus '(HCV)-Cured': n = 354/'HCV-Active': n = 179) of patients with HCV cirrhosis who underwent standardized ultrasound surveillance. In the main analysis, the event of interest was de novo non-tumoural PVT and events known to modify its natural history (orthotopic liver transplantation, transjugular intrahepatic portosystemic shunt, death, tumoural PVT and anticoagulation) were considered as competing risk. Adjusted models were built using propensity scores for baseline covariates. Moreover, predictive factors were investigated by conventional multivariate analysis. RESULTS: Ten (2.8%) patients in the 'HCV-Cured' cohort developed a non-tumoural PVT during a median follow-up of 37.1 months, while 8 (4.5%) patients in the 'HCV-Active' cohort were diagnosed with non-tumoural PVT during a median follow-up of 42.2 months. High Child-Pugh score was the only independent risk factor for non-tumoural PVT development and stage A patients were at low risk. Importantly, HCV cure did not decrease the risk of non-tumoural PVT in inverse probability of treatment-weighted (IPTW) analysis (subdistribution hazard ratio: 1.31 (95% confidence interval [95% CI]: 0.43-3.97); P = .635). In contrast, SVR was associated with a substantial reduction in mortality (IPTW-adjusted sHR: 0.453 [95% CI: 0.287-0.715]; P < .001). CONCLUSIONS: The risk of non-tumoural PVT persists after HCV cure in patients with cirrhosis, despite improving survival. Even after aetiological cure, severity of liver disease remains the main determinant of non-tumoural PVT development.

Limited Liver or Lung Colorectal Cancer Metastases. Systemic Treatment, Surgery, Ablation or SBRT.

The prognosis for oligometastatic colorectal cancer has improved in recent years, mostly because of recent advances in new techniques and approaches to the treatment of oligometastases, including new surgical procedures, better systemic treatments, percutaneous ablation, and stereotactic body radiation therapy (SBRT). There are several factors to consider when deciding on the better approach for each patient: tumor factors (metachronous or synchronous metastases, RAS mutation, BRAF mutation, disease-free interval, size and number of metastases), patient factors (age, frailty, comorbidities, patient preferences), and physicians' factors (local expertise). These advances have presented major challenges and opportunities for oncologic multidisciplinary teams to treat patients with limited liver and lung metastases from colorectal cancer with a curative intention. In this review, we describe the different treatment options in patients with limited liver and lung metastases from colorectal cancer, and the possible combination of three approaches: systemic treatment, surgery, and local ablative treatments.

Evaluation of LI-RADS 3 category by magnetic resonance in US-detected nodules ≤ 2 cm in cirrhotic patients.

OBJECTIVES: Liver Imaging Reporting and Data System (LI-RADS) for hepatocellular carcinoma (HCC) diagnosis in high-risk patients is a dynamic system, which was lastly updated in 2018. We aimed to evaluate the accuracy for HCC diagnosis of LI-RADS v2018 with magnetic resonance imaging (MRI) with extracellular contrast for solitary nodules ≤ 20 mm detected during ultrasound (US) surveillance in cirrhotic patients, with particular interest in those observations categorized as LI-RADS 3. METHODS: Between November 2003 and February 2017, we included 262 consecutive cirrhotic patients with a newly US-detected solitary ≤ 20-mm nodule. A LI-RADS (LR) v2018 category was retrospectively assigned. The diagnostic accuracy for each LR category was described, and the main MRI findings associated with HCC diagnosis were analyzed. RESULTS: Final diagnoses were as follows: 197 HCC (75.2%), 5 cholangiocarcinoma (1.9%), 2 metastasis (0.8%), and 58 benign lesions (22.1%); 0/15 (0%) LR-1, 6/26 (23.1%) LR-2, 51/74 (68.9%) LR-3, 11/12 (91.7%) LR-4, 126/127 (99.2%) LR-5, and 3/8 (37.5%) LR-M were HCC. LR-5 category displayed a sensitivity and specificity of 64% (95% CI, 56.8-70.7) and 98.5% (95% CI, 91.7-100), respectively. Considering also LR-4 as diagnostic for HCC, the sensitivity slightly increased to 69.5% (95% CI, 62.6-75.9) with minor impact on specificity (96.2%; 95% CI, 89.3-99.6). Regarding LR-3 observations, 51 out of 74 were HCC, 2 were non-HCC malignancies, and 20 out of 21 LR-3 nodules > 15 mm (95.2%) were finally categorized as HCC. CONCLUSIONS: The high probability of HCC in US-detected LR-3 observations (68.9%) justifies triggering an active diagnostic work-up if intended to diagnose HCC at a very early stage. KEY POINTS: • In cirrhotic patients with nodules ≤ 20 mm detected during US surveillance, 51 out of 74 (68.9%) of LR-3 nodules by MRI corresponded to an HCC. • In LR-3 nodules, HCC diagnosis was closely related to baseline tumor size. All 5 nodules smaller than 1 cm were diagnosed as benign. Oppositely, 20 out of 21 LR-3 observations > 15 mm (95.2%) were diagnosed as HCC. • The high probability of HCC in US-detected LR-3 observations justifies triggering an active diagnostic work-up if intended to diagnose HCC at a very early stage.

Performance of gadoxetic acid MRI and diffusion-weighted imaging for the diagnosis of early recurrence of hepatocellular carcinoma.

OBJECTIVE: To determine the diagnostic accuracy and predictive value of gadoxetic acid liver MRI (Gd-EOB-DTPA MRI) alone or in combination with diffusion-weighted imaging (DWI) as a second-line tool for detecting early hepatocellular carcinoma (HCC) recurrence in cirrhotic patients with previous HCC treated with resection or ablation. METHODS: Between 2014 and 2017, we prospectively included 34 cirrhotic patients with complete response to resection and/or ablation of early HCC in whom a new focal lesion enhancing in the arterial phase without washout was detected during follow-up with EC-MRI. After signing the informed consent, all patients underwent DWI and Gd-EOB-DTPA MRI; two readers analyzed signal intensities on each phase of dynamic study and on DWI. The final diagnosis was established by histology or follow-up EC-MRI. We used cross-tabulation to calculate indices of diagnostic accuracy. RESULTS: We evaluated 34 patients (7 women; 73.5% with hepatitis C virus) with a total of 53 new arterial-phase-enhancing foci (median size, 10 [IQR 9-14] mm). The final diagnosis, reached by histopathology in 15 (35.7%) lesions and EC-MR follow-up in 27 (64.3%), was HCC in 42 (79.2%) and benign conditions in 11 (21.8%). Hepatobiliary-phase hypointensity on Gd-EOB-DTPA MRI plus hyperintensity on DWI yielded 54.8% sensitivity, 90.9% specificity, 95.8% positive predictive value, and 34.5% negative predictive value for diagnosing HCC recurrence. CONCLUSION: Among potential indices, combining hypointensity on hepatobiliary-phase Gd-EOB-DTPA MRI and hyperintensity on DWI has the highest specificity and positive predictive value to optimally detect HCC recurrence prior to confident diagnosis by conventional imaging criteria on EC-MRI in cirrhotic liver. KEY POINTS: • In patients at risk of HCC recurrence, the use of gadoxetic acid liver MRI and DWI may improve the differentiation of unspecific new arterial-enhancing foci from early hypervascular HCC recurrence in patients with non-conclusive findings on extracellular liver MRI. • Combined findings on hepatobiliary-phase gadoxetic acid-enhanced liver MRI and DWI had high specificity (90.9%) and positive predictive value (95.8%) for detecting early hypervascular HCC recurrence, but limited sensitivity. • Combining hepatobiliary-phase hypointensity on gadoxetic acid MRI and hyperintensity on diffusion-weighted imaging allows early diagnosis of hypervascular hepatocellular carcinoma and may help select patients for salvage therapy.

Thermal Ablation for Intrahepatic Cholangiocarcinoma in Cirrhosis: Safety and Efficacy in Non-Surgical Patients.

PURPOSE: To assess the effectiveness, safety, and overall survival (OS) of thermal ablation as upfront treatment of intrahepatic colangiocarcinoma (ICC) in patients with cirrhosis. MATERIALS AND METHODS: This was a retrospective analysis of all biopsy-confirmed ICC in cirrhotic patients treated in the authors' unit from 2001 to 2017. Baseline characteristics, ablation procedures, and complications were recorded, and time to recurrence (TTR) and OS were calculated. Twenty-seven patients were identified. Seventy percent had Child-Pugh A disease, and most had clinically significant portal hypertension. Median tumor size was 21 mm. Twenty-one cases were uninodular, and 10 were single ≤ 2 cm. RESULTS: Complete radiologic necrosis was achieved in 25 cases (92.6%). Median OS was 30.6 months (95% confidence interval [CI], 22.6-46.5), and recurrence was detected in 21 cases (77.8%) with a TTR of 10.1 months (95% CI, 7.7-20.9). In those patients with single ≤ 2-cm ICC, the OS was 94.5 months (95% CI, 11.7-not reached). Differences in OS were statistically significant between patients with single ICC ≤ 2 cm and patients with single ICC > 2 cm (P = .04) and between patients with single ICC > 2 cm and patients with multinodular ICC (P = .02). Only 1 patient had a treatment-related complication. CONCLUSIONS: Thermal ablation is a safe and effective treatment for ICC in patients with cirrhosis who are not candidates for surgery. The OS is similar to that reported in surgical series, but the initial treatment success is hampered by a high rate of tumor recurrence. Encouraging long-term survival after thermal ablation is achieved in patients with single ≤ 2-cm ICC.

Prospective evaluation of gadoxetic acid magnetic resonance for the diagnosis of hepatocellular carcinoma in newly detected nodules ≤2 cm in cirrhosis.

BACKGROUND AND AIMS: Most of the published studies about the diagnostic accuracy of gadoxetic acid-enhanced magnetic resonance (EOB-MR) for the non-invasive diagnosis of hepatocellular carcinoma (HCC) have had a retrospective design. Thus, we aimed to prospectively evaluate the diagnostic accuracy of EOB-MR for the non-invasive diagnosis of HCC in nodules ≤2 cm detected by screening ultrasound (US) in patients with cirrhosis. METHODS: Between July 2012 and October 2015, 62 consecutive asymptomatic Child-Pugh A-B cirrhotic patients with newly US-detected solitary nodules between 1 and 2 cm were prospectively included in the study. Hepatic extracellular contrast-enhanced MR (ECCE-MR) followed by EOB-MR were obtained in less than 1-month interval. Two independent radiologists blindly reviewed the EOB-MR studies, and the diagnosis of HCC was assigned when the lesion showed arterial enhancement followed by portal venous phase washout and/or hypointensity on the hepatobiliary phase (HBP). The final HCC diagnosis was made by ECCE-MR according to the accepted non-invasive criteria, or by biopsy in lesions with atypical vascular profile. RESULTS: Final diagnoses were as follows: HCC (n = 41), intrahepatic cholangiocarcinoma (n = 2), colorectal metastases (n = 1) and benign conditions (n = 18). The sensitivity and specificity of EOB-MR for HCC diagnosis were 56.1% (95% CI: 39.7-71.5) and 90.5% (95% CI: 69.6-98.8), respectively, while sensitivity of ECCE-MR was 63.4% (95% CI: 46.9-77.9). The low rate of hypointense HCCs in the HBP and suboptimal liver uptake of contrast agent justify the low sensitivity of EOB-MR for HCC diagnosis. CONCLUSION: EOB-MR does not surpass the diagnostic accuracy of ECCE-MR for non-invasive diagnosis of HCC in nodules ≤2 cm in cirrhotic patients.