The text consists of two sections, one for those studying or practicing diagnostic radiology, nuclear medicine and radiation oncology; the other for those engaged in the study or clinical practice of radiation oncology--a new chapter, on radiologic terrorism, is specifically for those in the radiation sciences who would manage exposed individuals in the event of a terrorist event. The 17 chapters in Section I represent a general introduction to radiation biology and a complete, self-contained course especially for residents in diagnostic radiology and nuclear medicine that follows the Syllabus in Radiation Biology of the RSNA. The 11 chapters in Section II address more in-depth topics in radiation oncology, such as cancer biology, retreatment after radiotherapy, chemotherapeutic agents and hyperthermia.

Radiobiology for the Radiologist

The latest advances in hepatology were presented in oral and poster presentations. In order to cover the varying subspecialties, the sessions were divided into various sections including 'Acute Liver Failure and Artificial Liver Support', 'Biliary Tract and Immunologic Liver Diseases', 'Cellular and Molecular Biology', 'Clinical and Experimental Hepatobiliary Surgery', 'Hepatotoxicity and Cell Death', 'Transport and Biliary Physiology', 'Viral Hepatitis', 'Evaluation and Treatment of Biliary Disease', 'Necrosis/Apoptosis', 'Portal Hypertension', 'Blood Flow and Vascular Disorders of Cirrhosis', 'Liver Transplantation', 'Fibrogenesis', 'Hepatocellular Carcinoma', 'Metabolism and Genetic Disease', and 'Public Policy, Epidemiology and Decision Analysis'. Drug therapy focused on treatments for viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis, and recurrent viral disease following liver transplant. High dose interferon therapy or various combinations of interferon/ribavirin (ICN Pharmaceuticals Inc) therapy seem to offer the best current therapy for chronic HCV. PEGylated interferon (F Hoffmann-La Roche Ltd) offers hope for treatment and histologic improvement in patients with chronic HCV. Following liver transplantation, combination interferon/ribavirin therapy may also find success, but caution with new potent immunosuppressant monoclonal antibodies is advised. For HBV, intramuscular H-BIG (NABI) appears to be effective and less costly than iv H-BIG administration following liver transplantation. Percutaneous radiofrequency ablation may hold promise over conventional ethanol injection therapy for small hepatocellular carcinoma. Autoimmune hepatitis may respond to tacrolimus therapy whereas budesonide therapy did not provide any advantage to prednisone therapy. For primary biliary cirrhosis, eicosapentate and ursodeoxycholic acid may provide benefit to some patients while silymarin from milk thistle did not provide any additional benefit. In primary sclerosing cholangitis, high dose ursodeoxycholic acid may provide benefit. Ursodeoxycholic acid may also provide benefit for mothers with intrahepatic cholestasis of pregnancy by decreasing pruritus, lowering laboratory values and allowing deliveries to occur closer to term.

Digestive disease week 2000. American Association for the Study of Liver Diseases

Background & Aims
Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. The global HCC BRIDGE study was a multiregional, large-scale, longitudinal cohort study undertaken to improve understanding of real-life management of patients with HCC, from diagnosis to death.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/liv.12818

Global patterns of hepatocellular carcinoma management from diagnosis to death: The BRIDGE Study

Liver transplantation for hepatocellular carcinoma

The Liver Imaging Reporting and Data System (LI-RADS) is composed of four individual algorithms intended to standardize the lexicon, as well as reporting and care, in patients with or at risk for hepatocellular carcinoma in the context of surveillance with US; diagnosis with CT, MRI, or contrast material-enhanced US; and assessment of treatment response with CT or MRI. This report provides a broad overview of LI-RADS, including its historic development, relationship to other imaging guidelines, composition, aims, and future directions. In addition, readers will understand the motivation for and key components of the 2018 update.

https://pubs.rsna.org/doi/pdf/10.1148/radiol.2018181494

Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients.

Background/Aim: This study examined whether metformin can enhance the radiation response in a hepatocellular carcinoma (HCC) xenograft mice model and patient population. Materials and Methods: Huh-7 human HCC-bearing xenograft mice were treated with gamma-ray, metformin, neutron therapy, and their combinations. Tumour growth and lung colonies were assessed. Overall, 145 patients who underwent radiotherapy for HCC were retrospectively analysed. Results: The combinations of gamma-ray and metformin and neutron radiation and metformin inhibited tumour growth and metastatic lung nodule formation when compared to the monotherapy and gamma-ray groups, respectively. In patients who received radiotherapy for HCC, the overall survival rate was higher in the metformin-treated group than in the non-metformin group. Conclusion: Metformin inhibited tumour growth and metastasis in HCC by enhancing the radiation response in animal experiments. Additionally, metformin was also found to be associated with a higher survival outcome in patients with HCC.

Enhancement of Radiation Response Associated With Metformin in Hepatocellular Carcinoma: Preclinical Animal and Clinical Cohort Study

Abstract The primary motivation of this investigative study is trying to find an alternative treatment that can be used to slow down or treat glioblastoma due to the witnessed toxic side effects of the current drugs coupled with limited effectiveness in overall treatment. Consequently, a Chinese plant extract emodin proves to play a critical role in this investigative study since results from the Western blot and the other accompanying assays for anti-cancer effects indicate that it cannot work a lot to suppress cell migration and possible invasion, but rather emodin can be combined with radiation to give desired outcomes. Our result shows that the kind of radiation which acts well with emodin is neutron radiation rather than gamma radiation. Emodin significantly enhanced the radiosensitivity of LN18 and LN428 cells to γ-rays through MTT assay and cell counting. Accordingly, exposure to neutron radiation in the presence of emodin induced apoptotic cell death and autophagic cell death to a significantly higher extent, and suppressed cell migration and invasiveness more robustly. These effects are presumably due to the ability of emodin to amplify the effective dose from neutron radiation more efficiently. Thus, the study below is one such trial towards new interventional discovery and development in relation to glioblastoma treatment.

Emodin coupled with high LET neutron beam—a novel approach to treat on glioblastoma

Radiation-induced gastrointestinal (GI) damage is one of the critical factors that serve as basis for the lethality of nuclear accidents or terrorism. Further, there are no Food and Drug Administration-approved agents available to mitigate radiation-induced intestinal injury. Although pravastatin (PS) has been shown to exhibit anti-inflammatory and epithelial reconstructive effects following radiation exposure using mouse and minipig models, the treatment failed to improve the survival rate of high-dose irradiated intestinal injury. Moreover, we previously found that metformin (MF), a common drug used for treating type 2 diabetes mellitus, has a mitigating effect on radiation-induced enteropathy by promoting stem cell properties. In this study, we investigated whether the combined administration of PS and MF could achieve therapeutic effects on acute radiation-induced intestinal injury in mouse and minipig models. We found that the combined treatment markedly increased the survival rate and attenuated histological damage in a radiation-induced intestinal injury mouse model, in addition to epithelial barrier recovery, anti-inflammatory effects, and improved epithelial proliferation with stem cell properties. Furthermore, in minipig models, combined treatment with PS and MF ameliorates gross pathological damage in abdominal organs and attenuated radiation-induced intestinal histological damage. Therefore, the combination of PS and MF effectively alleviated radiation-induced intestinal injury in the mouse and minipig models. We believe that the combined use of PS and MF is a promising therapeutic approach for treating radiation-induced intestinal injury.

Combined Administration of Pravastatin and Metformin Attenuates Acute Radiation-Induced Intestinal Injury in Mouse and Minipig Models

The effects of mild-temperature hyperthermia (MTH) and metformin, alone or in combination, on the efficacy of high-dose hypofractionated radiation against experimental tumors were investigated. FSaII fibrosarcoma grown subcutaneously in the hind legs of C3H mice was irradiated with a single 15 Gy dose using a 60Co irradiator. The radio frequency capacitive method was used to heat the tumors at 41.0°C for 30 min. Metformin was intraperitoneally (i.p.) administered daily to tumor-bearing mice at a dose of 150 mg/kg. The expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and programmed cell death-ligand 1 (PD-L1) were determined by immunohistochemical staining of the excised tumor tissues. The apoptosis of tumor cells in vivo was quantified by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and cleaved caspase-3 staining of the excised tumor tissues. Irradiation of tumors markedly increased the expression of HIF-1α, VEGF, and PD-L1, and MTH and metformin used either alone or in combination significantly abrogated the radiation-induced upregulation of these proteins. MTH and metformin alone or combined increased the radiation-induced apoptosis in tumor cells and enhanced the radiation-induced suppression of tumor growth. The findings indicated that the increased tumor response to 15 Gy irradiation by MTH and metformin alone or in combination was due, in part, to the abrogation of the radiation-induced upregulation of HIF-1α and its downstream targets VEGF and PD-L1.

The Efficacy of Radiation is Enhanced by Metformin and Hyperthermia Alone or Combined Against FSaII Fibrosarcoma in C3H Mice

‡,§ ‡ § Purpose: To evaluate the impact of postoperative radiotherapy on loco-regional failure in patients with vulvar carcinoma and to determine the treatment strategy for inguinal lymph nodes. Materials and Methods: Sixty-six patients who received treatment for primary vulvar carcinoma at Seoul National University Hospital, from October 1979 through June 2004, were retrospectively analyzed. Sixteen patients were excluded from the analysis due to the following reasons: distant metastases in two patients; palliative intent for six patients; previous radiotherapy given to the pelvis in three patients; follow-up loss after surgery for four patient; insufficient medical records for one patient. Of 50 eligible patients, 35 were treated with surgery alone (S), ten were treated with surgery followed by radiotherapy (S+RT), and five were treated with radiotherapy alone. Results: The 5-year overall survival (OS) and disease-free survival (DFS) rates of all patients were 91% and 78%, respectively. Twelve patients (26%) experienced treatment failures and the sites of initial failure were as follows: a primary site in eight patients; regional lymph nodes in three patients; the lung in one patient. Although risk factors for failure were more common in the S+RT group than the S group of patients (p ＜0.05), the DFS rates were similar for the two groups (5-year DFS rates, 78% vs. 83%, p=0.66). The incidences of occult lymph node metastases was 10%. Ten of 31 patients with clinically negative lymph nodes did not received inguinal lymph node dissection, but no patient experienced regional failure. Conclusion: Postoperative radiotherapy may have a potential benefit for patients with risk factors for failure. The omission of inguinal dissection or elective radiotherapy to the inguinal lymph nodes may be considered in low-risk patients with clinically negative lymph nodes.

Won Il Jang

Papers

Enhancement of Radiation Response Associated With Metformin in Hepatocellular Carcinoma: Preclinical Animal and Clinical Cohort Study

Emodin coupled with high LET neutron beam—a novel approach to treat on glioblastoma

Combined Administration of Pravastatin and Metformin Attenuates Acute Radiation-Induced Intestinal Injury in Mouse and Minipig Models

The Efficacy of Radiation is Enhanced by Metformin and Hyperthermia Alone or Combined Against FSaII Fibrosarcoma in C3H Mice

Management of Regional Lymph Nodes in Localized Vulvar Carcinoma