Radiation exposure from radiological procedures in liver transplant candidates with hepatocellular carcinoma.

PURPOSE: Candidates for liver transplantation (LT) with hepatocellular carcinoma (HCC) undergo a large number of diagnostic and interventional radiology procedures. A significant proportion of such procedures involve ionizing radiation with increased lifetime risk of cancer. The objective of our study was to review LT candidates with HCC to quantify ionizing radiation doses from different radiology procedures performed at a single transplant center. METHOD: We retrospectively reviewed 179 adult patients with HCC (median age 58.6 years [IQR, 55-62]; 155 [86.6%] males) who were accepted for LT between April 2010 and Dec 2018. Radiology procedures and radiation doses were retrieved and the total and median radiation effective dose in millisieverts (mSv) were calculated for different procedures. Exposure to ionizing radiation was categorized based on previously reported thresholds. RESULTS: We assessed 9,986 radiology procedures for our cohort. Patients had a median effective dose prior to transplantation of 254 mSv (IQR, 130-421) with an annualized rate of 152 mSv (IQR, 92-266). Patient median dose increased to 316 mSv (IQR, 159-478) when including exposures post-LT within the study period. 85% of overall exposure was in the extremely high exposure category (>100 mSv). Interventional procedures represented 13% of procedures with substantial radiation and contributed to 45% of radiation exposure while abdominal CTs represented 39% of total procedures and contributed to 45% of radiation exposure. CONCLUSIONS: Patients with HCC considered for LT undergo radiology procedures with significant cumulative radiation exposure. Attempts to reduce radiation exposure are suggested by minimizing unnecessary procedures and utilizing ones without ionizing radiation. Improving interventional techniques to reduce radiation doses is needed without compromising treatment delivery.

Lenvatinib for the treatment of hepatocellular carcinoma-a real-world multicenter Australian cohort study.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia. METHODS: We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes. RESULTS: A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59-75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8-14.0) and 5.3 months (95% CI: 2.8-9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child-Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%). CONCLUSIONS: Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS.

Clinical outcomes of patients with two small hepatocellular carcinomas.

BACKGROUND: Management of single small hepatocellular carcinoma (HCC) is straightforward with curative outcomes achieved by locoregional therapy or resection. Liver transplantation is often considered for multiple small or single large HCC. Management of two small HCC whether presenting synchronously or sequentially is less clear. AIM: To define the outcomes of patients presenting with two small HCC. METHODS: Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC ≤ 3 cm between January 2000 and March 2018. Primary outcomes were overall survival (OS) and transplant-free survival (TFS). RESULTS: 104 patients were identified (male n = 89). Median age was 63 years (interquartile range 58-67.75) and the most common aetiology of liver disease was hepatitis C (40.4%). 59 (56.7%) had synchronous HCC and 45 (43.3%) had sequential. 36 patients died (34.6%) and 25 were transplanted (24.0%). 1, 3 and 5-year OS was 93.0%, 66.1% and 62.3% and 5-year post-transplant survival was 95.8%. 1, 3 and 5-year TFS was 82.1%, 45.85% and 37.8%. When synchronous and sequential groups were compared, OS (1,3 and 5 year synchronous 91.3%, 63.8%, 61.1%, sequential 95.3%, 69.5%, 64.6%, P = 0.41) was similar but TFS was higher in the sequential group (1,3 and 5 year synchronous 68.5%, 37.3% and 29.7%, sequential 93.2%, 56.6%, 48.5%, P = 0.02) though this difference did not remain during multivariate analysis. CONCLUSION: TFS in patients presenting with two HCC ≤ 3 cm is poor regardless of the timing of the second tumor. All patients presenting with two small HCC should be considered for transplantation.

Very Delayed Acute Hepatitis after Pembrolizumab Therapy for Advanced Malignancy: How Long Should We Watch?

Immune checkpoint inhibitors (ICIs) have led to major therapeutic advances in the management of malignancy. Despite promising outcomes for some cancers, ICIs are linked to unique side-effects known as immune-related adverse events (IrAEs). These may affect a wide array of organ systems. In particular, ICI-induced hepatitis is diagnostically challenging given its variable natural history and clinical manifestations. The onset of ICI-induced hepatitis often occurs between 6 and 14 weeks after treatment initiation and rarely exhibits delayed presentations or manifests after treatment cessation. We present a case of very delayed-onset ICI-induced hepatitis, stressing the importance of long-term surveillance for immune-indued hepatitis in patients initiated on ICIs even long after treatment cessation.

Value of Bone Scans in Work-up of Patients With Hepatocellular Carcinoma for Liver Transplant.

BACKGROUND: The purpose of this study was to review the value of bone scans (BS) in the assessment of bone metastases from early-stage hepatocellular carcinoma (HCC) in patients assessed or waiting for liver transplant (LTx). METHODS: We reviewed BS studies performed at our center for patients with early-stage HCC either being assessed for LTx, or on the waiting list for LTx, from January 2010 to May 2017. The BS findings were classified as positive, equivocal, or negative. Correlation with final outcome based on clinical and radiological follow-up was performed. RESULTS: There were 360 BS performed in 186 patients during the study period with a mean age of 58.7 years (range, 34.9-70.4 years) and most were male patients (161/186 [86.6%]). None of the BSs resulted in delisting of patients from the LTx waiting list. Three BSs were reported as positive for metastases. All 3 were proven to be false positives on follow-up. Fourteen studies reported equivocal findings, none of which were confirmed to be metastases on follow-up. There was 1 false-negative BS: a bone metastasis was detected incidentally on magnetic resonance imaging and proven on biopsy. CONCLUSIONS: We have demonstrated that the diagnostic yield of BS in early HCC patients who are candidates for LTx is minimal, challenging the current inclusion of BS in guidelines for staging these HCC patients.

Guillain-Barré syndrome in association with antitumour necrosis factor therapy: a case of mistaken identity.

Guillain-Barré syndrome (GBS) is an immune-mediated disease characterised by evolving ascending limb weakness, sensory loss and areflexia. Two-thirds of GBS cases are associated with preceding infection. However, GBS has also been described in association with antitumour necrosis factor (TNF) therapies including infliximab and adalimumab for chronic inflammatory disorders such as rheumatoid arthritis, ankylosing spondylitis and inflammatory bowel disease. We present the case of a patient who developed GBS while undergoing treatment with adalimumab in combination with azathioprine for severe fistulising Crohn's disease, and review the literature on neurological adverse events that occur in association with anti-TNF therapy. We also propose an approach to the optimal management of patients who develop debilitating neurological sequelae in the setting of anti-TNF therapy.