A case of concomitant EGFR/ALK alteration against a mutated EGFR background in early-stage lung adenocarcinoma

Rare cases of lung adenocarcinoma (LUAD) with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation have been reported. However, their clonal and evolutional relationship remains unclear. We report a case of early-stage EGFR-mutated LUAD with a focal concomitant EGFR/ALK alteration. A 63-year-old male underwent lobectomy to remove a 1.9-cm-sized lung nodule, which was diagnosed with EGFR-mutated LUAD. ALK immunohistochemistry (IHC) showed focal positivity within the part of the tumor characterized by lepidic pattern, also confirmed by fluorescence in-situ hybridization (FISH). Targeted next-generation sequencing was performed separately on the ALK IHC/FISH-positive and -negative areas. EGFR L833V/L858R mutations were detected in both areas, whereas EML4 (echinoderm microtubule-associated protein-like 4)-ALK translocations was confirmed only in the ALK IHC/FISH-positive area, suggesting the divergence of an EGFR/ALK co-altered subclone from the original EGFR-mutant clone. Our study suggests that concurrent alterations of EGFR and ALK can arise via divergent tumor evolution, even in the relatively early phases of tumorigenesis.

Long-term follow-up of optic neuritis associated with meningoencephalitis of unknown etiology in a Maltese dog

A 6-year-old intact male Maltese dog presented with a history of blindness and ataxia. Neuro-ophthalmic examination revealed dilated pupils with absent pupillary light reflexes and menace response in both eyes. Mild peripapillary edema was noted in the fundus of the right eye. After magnetic resonance imaging, the dog was provisionally diagnosed with meningoencephalitis of unknown etiology. Follow-up funduscopy was performed to monitor the condition of the optic discs for three years. Despite of the treatment with prednisolone, the optic nerve progressed to atrophy and the dog couldn't restore vision.

Long-term follow-up of optic neuritis associated with meningoencephalitis of unknown etiology in a Maltese dog / 대한수의학회지

A 6-year-old intact male Maltese dog presented with a history of blindness and ataxia. Neuro-ophthalmic examination revealed dilated pupils with absent pupillary light reflexes and menace response in both eyes. Mild peripapillary edema was noted in the fundus of the right eye. After magnetic resonance imaging, the dog was provisionally diagnosed with meningoencephalitis of unknown etiology. Follow-up funduscopy was performed to monitor the condition of the optic discs for three years. Despite of the treatment with prednisolone, the optic nerve progressed to atrophy and the dog couldn't restore vision.

Thoracolumbar Paraspinal Myonecrosis after Aortic Dissection / 대한신경손상학회지

Thoracolumbar paraspinal myonecrosis can be developed with various etiologies. It can induce compartment syndrome of spinal muscles and cause elevated pressure on back muscles, resulting in severe back pain. Thoracolumbar paraspinal myonecrosis is a very rare disease. There are only a few studies about paraspinal myonecrosis. Here we report a case of a spontaneous thoracolumbar paraspinal myonecrosis in a patient who had asymptomatic abdominal aortic dissection. Through this case, etiologies, clinical features, radiologic findings, and treatment options for thoracolumbar paraspinal myonecrosis are discussed.

Assessment of experimental saccular aneurysm using selective angiography in common carotid artery of rabbits / 대한해부학회지

In order to study the treatment of aneurysms, the technique of making experimental aneurysms in laboratory animals must be established. In our study, to examine the feasibility of making experimental aneurysm and selective angiography on the common carotid artery in rabbits and to determine the size of experimental aneurysm after surgery, saccular aneurysms were fashioned on the right common carotid artery in 17 rabbits using a vein pouch technique. Selective angiography of the common carotid artery was performed immediately after surgery, and at 1 week, 4 weeks, and 8 weeks after surgery. Also, histological changes in the aneurysms were observed. In 16 rabbits with established successful experimental aneurysm, no differences were found in diet intake and behavior before and after surgery. The patency of the carotid artery was confirmed by selective angiography. The average size of the aneurysm immediately after surgery was similar to that of 1 week postoperatively in selective angiography, however it increased with time at 4weeks and 8 weeks. Histologically, infiltration of inflammatory cells and hemorrhage were found at the junction of the carotid artery and the vein pouch at 1 week, which disappeared at 4 weeks and 8 weeks. This study suggests experimental saccular aneurysm using the vein pouch technique might form aneurysms similar to that of the human in its properties such as increment of size, and selective angiography might be suitable for assessment of experimental aneurysm. Therefore, this animal model may be suitable for investigating new treatment methodologies for human aneurysms.

The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

OBJECTIVE: The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. MATERIALS AND METHODS: This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. RESULTS: The tumor necrosis rate was significantly higher in the high dose group (93% +/- 7.6 [mean +/- SD]) than that in the control group (48% +/- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +/- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +/- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. CONCLUSION: Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.

Morphometric Studies in the Leydig Cell of Hemicastrated Rats / 체질인류학회지

The present study was conducted to investigate the influence of hemicastration and age at hemicastraion on the subsequent Leydig cell morphology and function of male rats. Sprague Dawley rats were left intact or hemicastrated at 20, 30, 40, 50, or 60 days of age (n=18 rats per group). At 100 days of age, all rats were sacrificed. Testes were fixed by whole body perfusion using a fixative containing 2.5% glutaraldehyde in cacodylate buffer, processed and embedded in Epon-araldite. Using 1 micrometer sections stained with methylene blue, qualitative and quantitative morphological studies were performed. Testis incubations were used to determine lutenizing hormone (LH; 100 ng/mL) stimulated testosterone secretory capacity per testis in vitro. Testosterone levels in the incubation medium, and testosterone and LH levels in serum of these six groups of rats were determined by radioimmunoassay. Body and testis weights were not changed by hemicastration between experimental and control groups. Volume density of seminiferous tubules, interstitium, and Leydig cells was not significantly affected by hemicastration. Absolute volume of seminiferous and interstitium was significantly increased in unilaterally castrated rats at 20, 30 and 40 days of age compared to control. Significant increases in the total number of Leydig cells per testis occurred in rats hemicastrated at 20, 30, 40 and 50 days of age compared to control. A significant increase in average volume of a Leydig cell was noted in the hemicastrated rats at 30 and 40 days compared to intact rats of the same age but was significantly decreased at 60 days of age. Serum testosterone levels and LH-stimulated testosterone production per testis were significantly (P<0.05) increased in the hemicastrated rats at 30 and 40 days. In summary, when rats were unilaterally castrated at 20, 30, 40, 50, and 60 days of age, those rats hemicastrated at 30 and 40 days showed compensatory hypertrophy/hypersecretion of Leydig cells when killed at 100 days of age. Especially, these data suggested that compensatory hypertrophy/hypersecretion of Leydig cells in rats hemicastrated around the time of puberty occurs in the remaining testis.

Comparison of Radiofrequency Ablation Lesion Size with Occlusion of Renal Vessels in Rabbit Kidneys: Occlusion of Renal Artery, Vein, and Both Vessels

PURPOSE: The purpose of this study was to compare the in-vivo efficiency of vascular occlusion on radiofrequency ablation (RFA) lesion size in a rabbit kidney model. MATERIALS AND METHODS: RFA lesions were created in a single kidney in 20 rabbits using an internally cooled electrode. Twenty ablation zones (1 per kidney) were created using 4 different regimens: RFA without vascular occlusion (n = 5), RFA with renal artery occlusion (n = 5), RFA with renal vein occlusion (n = 5), RFA with renal artery and vein occlusion (n = 5). Seven days later, the rabbits were sacrificed and the lesions were excised. These groups were then compared with respect to the dimensions of the ablation zones and the changes in impedance and current during RFA. RESULTS: The maximum ablation zone width was the greatest in the renal artery and vein occlusion group (21.0+/-1.4 mm), followed by the renal artery occlusion group (17.8+/-1.0 mm), the renal vein occlusion group (17.4+/-1.1 mm), and the nonocclusion group (7.8+/-2.4 mm) (p < 0.05). No significant differences were observed for impedances and currents between the 4 groups. CONCLUSION: Vascular occlusion combined with RFA effectively increased ablation zone dimensions compared with RFA alone, and the best effect was accomplished by combined renal artery and vein occlusion.

Assessment of Lymph Node Metastases by Contrast-Enhanced MR Imaging in a Head and Neck Cancer Model

OBJECTIVE: We wanted to investigate the accuracy of contrast-enhanced MR imaging for the detection of lymph node metastases in a head and neck cancer rabbit model. MATERIALS AND METHODS: The metastatic lymph node model we used was created by inoculating VX2 tumors into the auricles of six New Zealand White rabbits. T1-weighted MR images were obtained before and after injecting gadopentetate dimeglumine at three weeks after tumor cell inoculation. The sizes, signal intensity ratios (i.e., the postcontrast signal intensities of the affected nodes relative to the adjacent muscle) and the enhancement patterns of 36 regional lymph nodes (parotid and caudal mandibular nodes) were evaluated on MR images and then compared with the histopathologic findings. RESULTS: No statistical difference was found between the sizes of 12 metastatic (10.5+/-3.2 mm) and 24 hyperplastic (8.0+/-3.6 mm) lymph nodes (p > 0.05). On the contrast-enhanced T1-weighted MR images, nine metastatic and four hyperplastic lymph nodes had peripheral high and central low signal intensity, whereas three metastatic and 20 hyperplastic lymph nodes had homogeneous high signal intensity. Using a signal intensity ratio less than one as a diagnostic criterion for a metastatic lymph node, the sensitivity, specificity and positive and negative predictive values of the enhanced MR images were 75% (9/12), 83% (20/24), 69% (9/13) and 87% (20/23), respectively, with areas under receiver-operating-characteristic curve values of 0.81. CONCLUSION: This experimental study confirms that metastatic and hyperplastic lymph nodes can be differentiated using MR images on the basis of the contrast uptake patterns, but that they cannot be differentiated using any particular size criteria.

A Case of Mesenchymal Hamartoma

An one-day-old female patient was admitted due to marked abdominal distension, cyanosis, right upper quadrant mass, and respiratory failure since birth. We applied ventilator and supportive care immediatly. However, 4 days later, she was dead due to respiratory failure and hemorragic complication. The radiographic finding showed a huge intra-abdominal mass anterior to the intestine. Autopsy findings showed a huge single cystic tumor in the right lobe of the liver. The cysts were filled with sanguinous fluid. There wasn't any signs of necrosis or calcification. Microscopically, the tumor was well demarcated from the adjacent hepatic parenchyma. It consists of connective tissue with dilated lymphatics, vessels, and bile ducts.

Initial experience of transurethral radiofrequency thermotherapy for benign prostatic hyperplasia / 대한비뇨기과학회지

Transeurethral Radiofrequency (TURF) Thermotherapy is a new acceptable treatment modality for benign prostatic hyperplasia. We treated 70 cases of BPH patients by TURF Thermotherapy (THERMEX-II). Among them, we got a follow-up observation on 37 patients (urinary retention: 16 cases, non-urinary retention:21 cases) each at 1 month and 3 months after treatment. Mean age of patients was 69.1 years and their mean prostatic weight was 40.5gr by transrectal prostatic ultrasonogram. All patients were treated single session for 2 hours without any sedation, and well tolerated with the temperature of 47-48degree. We evaluate patients with Boyarsky symptom score, urine flow rate, volume of residual urine and patient`s subjective symptoms before and after treat- The results were as follows ; 1. The mean Boyarsky symptom score was 15.4 before treatment, it became 9.9 at 1 month and 8.8 at 3 months after treatment. 2. In the retention patients : Mean maximal flow rate was 6.53ml/sec at 1 month. 8.47ml/sec at 3 months, and residual urine was 70ml at 1 month, 57ml at 3 months after treatment. 3. In the non-retention patients : Mean maximal flow rate increased from 4.74ml/sec to 10.29ml/ sec at 1 month. 10.76ml/sec at 3 months, and residual urine decreased from 60.7ml/ to 20ml at 1 month. 17.2ml at 3 months after treatment. 4. Complications were acute urinary retention (14.3% ) and gross hematuria (8.1%), but it was resolved by conservative treatment. There were no urinary tract infection, bladder spasm or other complications after treatment. We conclude TURF thermotherapy is one of the good and safe treatment in benign prostatic hyperplasia.

Clear cell carcinoma of bladder invading the posterior urethra / 대한비뇨기과학회지

Clear cell carcinoma of the bladder and urethra is very rare entity with its origin unclear. The typical location in the bladder neck and trogon tends to confirm that this neoplasm probably derives from a remnant of the mesonephric duct. But Mullerian remnants or metaplastic paraurethral elands may be the source of origin. We experienced a case of clear cell carcinoma of the bladder invading the posterior urethra occurring in a 68-year-old female treated by radical cystourethrectomy and ileal conduit diversion and 16 month later. we found a hard, fixed, palpable metastatic nodule in the left neck area. Herein we report a metastatic case of clear cell carcinoma or the bladder invading the posterior urethra with review of the literature.

Experimental Study on Cerebral Cysticercosis

Cerebral cysticercosis may produce many complications and various types of tissue reactions to the parenchyma of the brain. The purpose of the present investigation was to study the nature of the reactions of the brain tissue responding to a direct contract with the fluid contents of cysticercus cyst. The experiments were performed in 15 albino rats in which the brain lesions were made on the frontal region by injecting the fluid contents which was obtained from subcutaneous nodules of human patient with cysticercosis. The fluid contents, 0.5 ml for each animal, was injected with 26 gauge hypodermal needle into the left cerebral hemisphere beneath the cortex for experimental group, and same amount of normal saline into the right hemisphere indentical to the region of the left for the control group. Histopathological studies were carried out on the brain lesions at interval of 3 days, 7 days and 15 days following injection of the contents and normal saline. Findings of generalized and regional edema of the brain were observed in varying degrees, which were evident and severe in 3-day and 7-day experimental groups and decreasing in severity thereafter. In the group of normal saline injection, the microscopic findings of the lesions were mainly of a mild inflammatory reactions with scattered fibroblast or condensation of the nervous tissue. In 3-day experimental group, there were pleomorphic infiltration of neutrophils and histiocytes. In 7-day experimental group, there were prominent cellular reaction, gliosis and vascular proliferation more than those observed in 3-day group. In 15-day experimental group, inflammatory cells and gliosis were reduced in number and degree, but definitive granuloma with proliferation of vascular fibroblast in its outer layer was developed.