FLASH Radiotherapy: A FLASHing Idea to Preserve Neurocognitive Function

FLASH radiotherapy (FLASH RT) is a technique to deliver ultra-high dose rate in a fraction of a second. Evidence from experimental animal models suggest that FLASH RT spares various normal tissues including the lung, gastrointestinal track, and brain from radiation-induced toxicity (a phenomenon known as FLASH effect), which is otherwise commonly observed with conventional dose rate RT. However, it is not simply the ultra-high dose rate alone that brings the FLASH effect. Multiple parameters such as instantaneous dose rate, pulse size, pulse repetition frequency, and the total duration of exposure all need to be carefully optimized simultaneously. Furthermore it is critical to validate FLASH effects in an in vivo experimental model system. The exact molecular mechanism responsible for this FLASH effect is not yet understood although a number of hypotheses have been proposed including oxygen depletion and less reactive oxygen species (ROS) production by FLASH RT, and enhanced ability of normal tissues to handle ROS and labile iron pool compared to tumors. In this review, we briefly overview the process of ionization event and history of radiotherapy and fractionation of ionizing radiation. We also highlight some of the latest FLASH RT reviews and results with a special interest to neurocognitive protection in rodent model with whole brain irradiation. Lastly we discuss some of the issues remain to be answered with FLASH RT including undefined molecular mechanism, lack of standardized parameters, low penetration depth for electron beam, and tumor hypoxia still being a major hurdle for local control. Nevertheless, researchers are close to having all answers to the issues that we have raised, hence we believe that advancement of FLASH RT will be made more quickly than one can anticipate.

Comparison of adhesive strength of resinous teeth splinting materials according to enamel surface treatment

PURPOSE: The purpose of this study is to compare and analyze the shear bond strength and fracture pattern in different enamel tooth surface treatments for resin splinting materials. MATERIALS AND METHODS: G-FIX and LightFix were used as tooth splinting materials. Twenty bovine mandibular incisors were used for the preparation of the specimens. The exposed enamel surface was separated into four parts. Each tooth was treated with 37% phosphoric acid, 37% phosphoric acid + adhesive resin, 37% phosphoric acid + G-premio bond, and G-premio bond for each fraction. Shear bond strength was measured using a universal testing machine. After measuring the shear bond strength, the fractured surface of the specimen was magnified with a microscope to observe the fracture pattern. Two-way ANOVA was used to verify the interaction between the material and the surface treatment method. Oneway ANOVA was used for comparison between the surface treatment methods of each material and post-hoc test was conducted with Scheffe's test. An independent t-test was conducted to compare shear bond strengths between materials in each surface treatment method. All statistics were conducted at 95% significance level. RESULTS: G-FIX, a tooth splinting resin, showed similar shear bonding strength when additional adhesive resins were used when material was applied after only acid etching, and LightFix showed the highest shear bonding strength when additional adhesive resins were used after the acid etching. In addition, both G-FIX and LightFix showed the lowest shear bond strength when only self-etching adhesive was applied without additional acid etching. Verification of interactions observed interconnection between resins and surface treatment methods. Most of the mixed failure was observed in all counties. CONCLUSION: When using G-FIX and LightFix, which are tooth-splinting materials, it is considered that sufficient adhesion will be achieved even after applying only acid etching as instructed by the manufacturer.

A Case of Cholangiocarcinoma with Brain and Leptomeningeal Carcinomatosis / 대한내과학회지

Cholangiocarcinoma is a malignant disease originating from the epithelium of the biliary tract, and its prognosis is dismal due to distant metastasis in its early stages. The most common metastatic sites are the intra-abdominal organs, lymph nodes, and lungs. A patient was diagnosed with intrahepatic cholangiocarcinoma and underwent surgical resection. During the follow-up period, metastases were detected at the remnant liver and both lung fields. Eleven months after resection, the patient complained of severe headache. An approximately 5-cm cystic mass was found at the left occipital lobe of the cerebrum, and metastatic malignant cells were present on cerebrospinal fluid cytology. The patient underwent whole-brain radiotherapy. We herein report a rare case of cholangiocarcinoma with cystic brain metastasis together with a review of the relevant literature.

Clinical characteristics and outcomes of primary bone lymphoma in Korea

BACKGROUND: This study evaluates the effectiveness of immunochemotherapy and radiation therapy in the treatment of patients with primary bone lymphoma (PBL). METHODS: We retrospectively reviewed the medical records of 33 patients with PBL who were treated at 6 medical centers in Korea from 1992 to 2010. Clinicopathological features and treatment outcomes were analyzed. RESULTS: The median age of the patients participating in our study was 40 years. The most common sites of involvement were the pelvis (12.36%) and femur (11.33%). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens were administered to 20 patients (61%), and R-CHOP (rituximab plus CHOP) was administered to the remaining 13 patients (39%). The overall response rate was 89% (complete response, 76%; partial response, 12%). The overall survival (OS) of patients with solitary bone lesions was longer than that of patients with multiple bone lesions (median OS: not reached vs. 166 months, respectively; P=0.089). Addition of rituximab to CHOP did not significantly affect either OS or progression-free survival (P=0.53 and P=0.23, respectively). Combining radiation therapy with chemotherapy also did not improve the OS or progression-free survival of patients with solitary bone lesions. CONCLUSION: Conventional cytotoxic chemotherapy remains an effective treatment option for patients with PBL. Additional benefits of supplementing chemotherapy with either rituximab or radiation therapy were not observed in this study. Further investigation is needed to characterize the role of immunochemotherapy in treating patients with PBL.

A Case of Cimetidine-induced Immune Hemolytic Anemia / 대한수혈학회지

There have been 5 case reports about immune hemolytic anemia related with cimetidine, but there has been no such report in Korea. A sixty-four-year-old woman was admitted to the emergency department in a coma. She was diagnosed with diffuse large B-cell lymphoma 5 years ago and she achieved a complete remission after treatment. She was in a state of shock, and her blood pressure was 70/40 mmHg. The laboratory test results were consistent with hemolytic anemia (HA) as follows: hemoglobin: 1.9 g/dL, corrected reticulocyte count: 2%, total/conjugated bilirubin: 6.4/2.1 mg/dL, lactate dehydrogenase: 1,083 U/L and haptoglobin <10 mg/dL. She had a history of taking the drugs including cimetidine, acetaminophen and etizolam for two days. She urgently received transfusion of 3 units of packed red blood cells and then she regained consciousness. To investigate the relation between cimetidine and HA, we subsequently performed a drug-induced immune complex test and an antibody test by using cimetidine, AB serum and phosphate-buffered saline. The results proved that cimetidine was the cause of the HA. Patient was treated with steroid, and the following laboratory tests showed rapid improvement. This is the first case report from Korea that shows the causal relationship between cimetidine and immune HA.

Primary cutaneous B-cell lymphoblastic lymphoma in an elderly man

Precursor B-cell lymphoblastic lymphoma (B-LBL) is an uncommon high-grade neoplasm of immature B cells. It occurs predominantly in childhood with extranodal involvement such as skin and bone. Therefore, primary cutaneous involvement in elderly adults is a very rare manifestation of B-LBL. Here, we report a 78-year-old man with B-LBL presenting as a single cutaneous lesion which was immunohistochemically positive for leukocyte common antigen (LCA), CD79a, paired box 5 (PAX5), B cell lymphoma-2 (bcl-2), and terminal deoxynucleotidyl transferase (TdT) staining, but was without systemic involvement. The patient was treated using cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP), and achieved complete response (CR) at the first response assessment conducted after 3 CHOP cycles. After an additional cycle of CHOP treatment, radiotherapy was administered at a total dose of 3,600 cGy over 4 weeks. At the 21-month follow-up, he had maintained CR.