Selective Internal Radiation Therapy for Hepatocellular Carcinoma Across the Barcelona Clinic Liver Cancer Stages.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common lethal cancer, and there is a need for effective therapies. Selective internal radiation therapy (SIRT) has been increasingly used, but is not supported by guidelines due to a lack of solid evidence. AIMS: Determine the efficacy and safety of SIRT in HCC across the Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C. METHODS: Consecutive patients that received SIRT between 2006 and 2016 at two centers in Canada were evaluated. RESULTS: We analyzed 132 patients, 12 (9%), 62 (47%), and 58 (44%) belonged to BCLC stages A, B, and C; mean age was 61.2 (SD ± 9.2), and 89% were male. Median survival was 12.4 months (95% CI 9.6-16.6), and it was different across the stages: 59.7 (95% CI NA), 12.8 (95% CI 10.2-17.5), and 9.3 months (95% CI 5.9-11.8) in BCLC A, B, and C, respectively (p = 0.009). Independent factors associated with survival were previous HCC treatment (HR 2.01, 95% CI 1.23-3.27, p = 0.005), bi-lobar disease (HR 2.25, 95% CI 1.30-3.89, p = 0.003), ascites (HR 1.77, 95% CI 0.99-3.13, p = 0.05), neutrophil-to-lymphocyte ratio (HR 1.11, 95% CI 1.02-1.20, p = 0.01), Albumin-Bilirubin (ALBI) grade-3 (HR 2.69, 95% CI 1.22-5.92, p = 0.01), tumor thrombus (HR 2.95, 95% CI 1.65-5.24, p < 0.001), and disease control rate (HR 0.62, 95% CI 0.39-0.96, p = 0.03). Forty-four (33%) patients developed severe adverse events, and ALBI-3 was associated with higher risk of these events. CONCLUSIONS: SIRT has the potential to be used across the BCLC stages in cases with preserved liver function. When using it as a rescue treatment, one should consider variables reflecting liver function, HCC extension, and systemic inflammation, which are associated with mortality.

Visceral Adipose Tissue Radiodensity Is Linked to Prognosis in Hepatocellular Carcinoma Patients Treated with Selective Internal Radiation Therapy.

Hepatocellular carcinoma (HCC) constitutes the fourth leading cause of cancer-related mortality. Various factors, such as tumor size, tumor multiplicity, and liver function, have been linked to the prognosis of HCC. The aim of this study was to explore the prognostic significance of muscle, subcutaneous and visceral adipose tissue (VAT) mass, and radiodensity, in a cohort of 101 HCC patients treated with selective internal radiation therapy (SIRT). Muscle and adipose tissue cross sectional area (cm2/m2) and radiodensity, reported as the Hounsfield Unit (HU), were determined using pre-SIRT computed tomography images. Cox proportional hazard models and exact logistic regression were conducted to assess associations between body composition and adverse outcomes. Majority of the patients were male (88%) with a mean VAT radiodensity of -85 ± 9 HU. VAT radiodensity was independently associated with mortality (HR 1.05; 95% CI: 1.01-1.08; p = 0.01), after adjusting for cirrhosis etiology, Barcelona Clinic Liver Cancer stage, previous HCC treatment, and portal hypertension markers. Patients with a high VAT radiodensity of ≥-85 HU had a two times higher risk of mortality (HR 2.01, 95% CI 1.14-3.54, p = 0.02), compared to their counterpart. Clinical features of portal hypertension were more prevalent in patients with high VAT radiodensity. High VAT radiodensity was associated with severe adverse events after adjusting for confounding factors. High VAT radiodensity is independently associated with both increased mortality and severe adverse events in patients treated with SIRT. VAT radiodensity measurement might serve as an objective approach to identify patients who will experience the most benefit from SIRT.

Canadian Association of Radiologists consensus guidelines for the prevention of contrast-induced nephropathy: update 2012.

PURPOSE: Contrast-induced acute kidney injury or contrast-induced nephropathy (CIN) is a significant complication of intravascular contrast medium (CM). These guidelines are intended as a practical approach to risk stratification and prevention. The major risk factor that predicts CIN is pre-existing chronic kidney disease. METHODS: Members of the committee represent radiologists and nephrologists across Canada. The previous guidelines were reviewed, and an in-depth up-to-date literature review was carried out. RESULTS: A serum creatinine level (SCr) should be obtained, and an estimated glomerular filtration rate (eGFR) should be calculated within 6 months in the outpatient who is stable and within 1 week for inpatients and patients who are not stable. Patients with an eGFR of ≥ 60 mL/min have an extremely low risk of CIN. The risk of CIN after intra-arterial CM administration appears be at least twice that after intravenous administration. Fluid volume loading remains the single most important measure, and hydration regimens that use sodium bicarbonate or normal saline solution should be considered for all patients with GFR < 60 mL/min who receive intra-arterial contrast and when GFR < 45 mL/min in patients who receive intravenous contrast. Patients are most at risk for CIN when eGFR < 30 mL/min. Additional preventative measures include the following: avoid dehydration, avoid CM when appropriate, minimize CM volume and frequency, avoid high osmolar CM, and discontinue nephrotoxic medications 48 hours before administration of CM.

Surveillance of a coiled renal artery aneurysm by contrast-enhanced ultrasound with Definity.

Imaging surveillance is necessary to assess for long-term procedural outcomes after endovascular treatment. This is generally performed by computed tomography (CT) or magnetic resonance imaging (MRI). Contrast-enhanced ultrasound (CEUS) has recognized utility for cardiovascular and abdominal applications and is an alternative option in patients with renal impairment or CT/MR contrast-related reactions. We believe that we present the first reported case of CEUS in the surveillance of a treated renal artery aneurysm. The 57-year-old patient had a severe CT contrast allergy. CEUS performed with Definity microbubble ultrasound contrast (Lantheus Medical Imaging, Billerica, Mass) was well tolerated and showed no residual filling of the aneurysm.

Lipophilic photosensitizer administration via the prostate arteries for photodynamic therapy of the canine prostate.

BACKGROUND: Current limitations of interstitial photodynamic therapy (PDT) for treatment of prostate cancer include low drug selectivity after intravenous (i.v.) administration and incomplete ablation of glandular tissue. To overcome these limitations, intra-arterial (i.a.) injection of a photosensitizer was tested in a canine model. METHODS: A lipophilic photosensitizer, SL052 formulated in liposomes or dissolved in dimethyl sulphoxide (DMSO), was injected into male dogs as an intravenous injection or intra-arterially via the prostate arteries. Optical fibers were inserted into the prostate 3h after i.v. or immediately following i.a. drug delivery. Laser light was delivered through the fibers in cycles controlled by a computer-driven switch. Drug concentration (fluorescence) and light transmission in prostate tissue were monitored during the course of PDT. Side effect profile and completeness of prostate gland ablation were the primary parameters compared among treatment groups. Control animals received drug-only or light-only treatment. RESULTS AND CONCLUSION: Thirteen dogs were treated by PDT mediated by i.a. injection of SL052 dissolved in DMSO and attained either complete ablation of prostatic glandular tissue or significant reduction of prostate volume compared with that of pre-PDT (p<0.0001). When compared to i.v. administration the i.a. route resulted in more complete photo-ablation. Associated side effect included acute urinary retention which resolved overtime. No incontinence was observed. With careful tailoring of PDT drug and light doses, interstitial PDT with i.a. injection of SL052-DMSO has the potential to provide effective treatment for prostate disease.

Ablative technologies in the management of patients with primary and secondary liver cancer: an overview.

Interventional ablative technologies have played an increasingly important role in the management of patients with primary or secondary liver malignancies. Ethanol and acetic acid ablation were the primary modalities available 2 decades ago. Today, several new technologies are available, including radiofrequency ablation, cryoablation, and microwave ablation. Radiofrequency ablation is the most widely practiced, however, cryoablation and microwave ablation are reasonable choices in certain situations. Irreversible electroporation is a newer technique, which has yet to enter clinical practice, but shows promising preliminary results. Herein, we provide a brief overview of the above-mentioned technologies with a focus on principles of ablation and technique. We also describe the use of these techniques in the context of cytoreduction, a noncurative approach aimed at reducing the overall tumour burden and providing concomitant survival benefit.

Role of imaging in clinical islet transplantation.

Islet transplantation is an innovative and effective clinical strategy for patients with type 1 diabetes whose clinical condition is inadequately managed even with the most aggressive medical treatment regimens. In islet transplantation, purified islets extracted from the pancreas of deceased donors are infused into the portal vein of the recipient liver. Engrafted islets produce insulin and thus restore euglycemia in many patients. After islet transplantation performed with the original Edmonton protocol, 80% of patients were insulin independent at 1 year and approximately 20% were insulin independent at 5 years. With more recent technical advances, 50% of patients or more maintain insulin independence 5 years after islet transplantation. The success rate with single-donor islet infusions has markedly improved over time. Even in patients who lose insulin independence, islet transplantation is considered successful because it provides improved glycemic control and a higher quality of life. Imaging plays an important role in islet transplantation and is routinely used to evaluate potential recipients, guide the transplantation process, and monitor patients for posttransplantation complications. Because of the success of islet transplantation and its increasing availability worldwide, familiarity with the role of imaging is important.

Embolization of musculoskeletal bone tumors.

Bone tumors may present as incidental findings, with pain or loss of function, or as fractures. There is a broad range of indications for transarterial embolization (TAE) in primary or metastatic bone tumors: to reduce operative hemorrhagic risks, to simplify or allow more definitive surgery, or in the context of pain palliation, fever, bleeding, or hypercalcemic and other rheological factors. Embolization may also increase tumor sensitivity to chemotherapy or radiation therapy. The procedure itself is often complex with significant risk to adjacent structures and is usually part of a wider treatment strategy. There are many options of embolic agent, techniques, and end points but all aim to devascularize the tumor. Catheter angiography at the time of TAE is used to determine the correct embolic agent and technique with care taken to isolate at risk structures. Many factors determine the best choice of embolic material, probably the most important of which is operator experience. In life-threatening situations or in preoperative embolizations of metastatic tumors, many operators opt for a combination of particulate emboli and stainless steel or platinum coils. Agents discussed include polyvinyl alcohol particles, trisacryl microspheres, gelatin sponge, liquid embolic agents, and embolization coils. Tumor types treated include vascular metastatic lesions, commonly renal cell or thyroid, particularly in locations prone to fracture; giant cell tumors; aneurysmal bone cysts; vertebral hemangiomas, osteosarcomas; arteriovenous malformations; and osteoblastomas. TAE should be considered in the treatment algorithm of primary or secondary bone tumors. Specific benefit is present where there is a high risk of bleeding at surgery, where there is spinal involvement and neural encroachment, where active bleeding is present or in awkward surgical locations where prolonged surgery is anticipated.

Effects of probiotic therapy on portal pressure in patients with cirrhosis: a pilot study.

BACKGROUND: Recent literature has supported the role of bacterial translocation as a mediator of splanchnic vasodilatation and portal hypertension. The objective of this study was to determine whether the probiotic VSL#3 would reduce portal pressure in patients with cirrhosis. METHODS: Eight patients with compensated or very early decompensated cirrhosis and hepatic venous pressure gradient (HVPG) >10 mmHg, received 2 months of VSL#3 (3600 billion bacteria daily). The HVPG, intestinal permeability, endotoxin, tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, renin and aldosterone were measured at baseline and study end. RESULTS: There was no change in the HVPG or intestinal permeability from baseline to study end but there was a trend to reduction in plasma endotoxin (P=0.09), a mild but significant increase in serum TNF-alpha (P=0.02) and a significant reduction in plasma aldosterone (P=0.03). CONCLUSIONS: Within the limitations of small sample size, there does not appear to be a benefit of probiotic therapy for portal pressure reduction in patients with compensated or early decompensated cirrhosis. The reductions in endotoxin and aldosterone suggest possible beneficial effects of probiotics for this patient population. The clinical significance of the small but unexpected increase in TNF-alpha is unclear. Future studies are planned in patients with decompensated cirrhosis.

Embolization of musculoskeletal tumors.

Transarterial embolization should be considered in the treatment algorithm of primary or secondary bone tumors. Specific benefit is present where there is a high risk of bleeding at surgery, where there is spinal involvement and neural encroachment, where active bleeding is present, or in awkward surgical locations where prolonged surgery is anticipated.

Canadian Association of Radiologists: consensus guidelines for the prevention of contrast-induced nephropathy.

The development of acute renal failure significantly complicates intravascular contrast medium (CM) use and is linked with high morbidity and mortality. The increasing use of CM, an aging population, and an increase in chronic kidney disease (CKD) will result in an increased incidence of contrast-induced nephropathy (CIN)-unless preventive measures are used. The Canadian Association of Radiologists has developed these guidelines as a practical approach to risk stratification and prevention of CIN. The major risk factor predicting CIN is preexisting CKD, which can be predicted from the glomerular filtration rate (GFR). In terms of being an absolute measure, serum creatinine (SCr) is an unreliable measure of renal function. Patients with GFR >60 mL/min have a very low risk of CIN, and preventive measures are generally unnecessary. When GFR is <60 mL/min, preventive measures should be instituted. The risk of CIN is greatest in patients with GFR <30 mL/min. Preventive measures: Alternative imaging that does not require CM should be considered. Fluid volume loading is the single most important protective measure. Nephrotoxic medications should be discontinued 48 hours prior to the study. CM volume and frequency of administration should be minimized, but satisfactory image quality should still be maintained. High-osmolar contrast should be avoided in patients with renal impairment. There is some evidence to suggest that iso-osmolar contrast reduces the risk of CIN among patients with renal impairment, but further study is necessary to determine whether iso-osmolar contrast is superior to low-osmolar contrast. Acetylcysteine (AC) has been advocated to reduce the incidence of CIN; however, not all studies have shown a benefit, and it is difficult to formulate evidence-based recommendations at this time. Its use may be considered in high-risk patients but is not considered mandatory.

Interstitial photodynamic therapy of the canine prostate using intra-arterial administration of photosensitizer and computerized pulsed light delivery.

PURPOSE: We determined the feasibility of complete treatment of the canine prostate and long-term effectiveness of interstitial photodynamic therapy using the intra-arterial photosensitizer QLT0074 (benzoporphyrin derivative 1,3-diene C,D-diethylene glycol ester A ring) (QLT, Vancouver, British Columbia, Canada) administration and pulsed light delivery. MATERIALS AND METHODS: The prostate gland of 11 dogs were infused with QLT0074 via the prostatovesical arteries (2 mg drug per artery bilaterally) under fluoroscopic guidance. Immediately following infusion the prostate was surgically exposed and 7 optical fibers with 1.5 cm cylindrical diffusers in after loading sheaths were inserted into the prostate through a template. Light was delivered sequentially to the optic fibers via a computer driven switch system. One dog was sacrificed 6 days after photodynamic therapy to assess acute tissue effects. The other 10 dogs were monitored for clinical tolerance and urinary function, and sacrificed at between 3 and 11 months. Prostate specimens were examined microscopically to evaluate long-term tissue reactions. RESULTS: Comprehensive destruction of the prostate was noted in the acute dog. Except for urinary retention and mild hematuria no other perioperative complications were observed in the chronic dogs. Urodynamic examination did not reveal deleterious bladder and urethral function. Average prostate volume decreased 71% at 3 months and 56% after 6 months (p=0.007 and 0.014, respectively). Microscopic evaluation revealed prostate glandular epithelial atrophy, stromal fibrosis and mononuclear cell infiltration. CONCLUSIONS: Interstitial photodynamic therapy using intra-arterial QLT0074 and pulsed light delivery is safe and feasible for comprehensive destruction of the canine prostate. Clinical trials are required to confirm it for managing prostate diseases.

Diagnosis of a bleeding Dieulafoy lesion on computed tomography and its subsequent embolization.

Dieulafoy lesions are a potentially serious cause of gastrointestinal bleeding. Because they may bleed intermittently, and only be endoscopically evident during hemorrhage, their diagnosis can be challenging. This is the first case to be reported in the English literature of a patient with a Dieulafoy lesion diagnosed during computed tomography (CT) examination. Reduced acquisition times required for multislice helical CT allow the application of CT angiography in the diagnosis of gastrointestinal bleeding. CT scans are now widely used in the diagnostic algorithm for acute gastrointestinal hemorrhage, and the present case illustrates that with fortuitous timing, they can provide critical information and an opportunity for selected angiography and coil embolization.

Percutaneous transhepatic pancreatic islet cell transplantation in type 1 diabetes mellitus: radiologic aspects.

PURPOSE: To report our experience with percutaneous transhepatic pancreatic islet cell transplantation in patients with type 1 diabetes mellitus. MATERIALS AND METHODS: Between March 1999 and May 2002, 34 patients underwent 68 islet cell transplantation procedures. Patients with C-peptide-negative type 1 diabetes were selected on the basis of poor metabolic control (hypoglycemia or lability) despite compliance with optimal medical therapy. Islet cells were isolated from brain-dead donors. Access to the portal vein was gained from a right percutaneous transhepatic approach, and islet cells were infused with intermittent pressure monitoring. Twenty patients underwent two transplantations, seven patients underwent three transplantations, and seven patients underwent one transplantation. Complications during and after the procedure and postprocedural diabetic status were monitored. RESULTS: Successful portal vein cannulation and islet cell infusion were achieved in all cases. Fluoroscopy was used as the primary guidance modality in 58 of 68 (85%) procedures, and ultrasonography was used in 10 of 68 (15%). Total recorded fluoroscopy time varied from 0.6 to 103 minutes, with a median of 6.9 minutes. Potentially serious complications occurred in six of 68 (9%) procedures. Two patients developed portal venous thrombosis, and with subsequent anticoagulation therapy, one of the two developed an expanding hepatic hematoma that required surgery. Clinically important hemorrhage occurred in four patients, three of whom required blood transfusions. Of 26 patients who received completed transplants, all became insulin independent, and 81% (21 of 26) remained insulin free at 1 year. CONCLUSION: The percutaneous transhepatic approach for the implantation of islet cells into the portal vein is a safe procedure, and together with use of current cell separation techniques and an immunosuppressive regimen, offers a marked advance in the treatment of type 1 diabetes mellitus.