Transcriptomic Analysis of Papillary Thyroid Cancer: A Focus on Immune-Subtyping, Oncogenic Fusion, and Recurrence

Objectives@#. Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer. @*Methods@#. This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database. @*Results@#. Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension). @*Conclusion@#. We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.

Helicobacter pylori testing in a population of Korean patients with pernicious anemia

No abstract available.

Long-term Survival after Repeated Local Therapy and Salvage Chemotherapy for Recurrent Metastases from Gastric Cancer: a Case Report and Literature Review

We report a rare case of long-term survival in a patient who received local therapy and salvage chemotherapy for recurrent metastases, along with a literature review. A 65-year-old male patient underwent subtotal gastrectomy for advanced gastric adenocarcinoma. Six months after gastrectomy, 2 metastatic intra-abdominal lymph node enlargements were detected, which were treated with radiotherapy. At 55 months after gastrectomy, an abdominal wall mass was detected, which was treated by surgical resection. The patient received 5-fluorouracil/leucovorin/irinotecan chemotherapy for 27 months before and after radiotherapy and docetaxel chemotherapy for 6 months after surgical resection of the abdominal wall metastasis. At the last visit, 7.8 years since the initial resection of the primary gastric cancer and 6.2 years since detection of the first metastases, the patient was disease-free and required no further chemotherapy. This case suggests that repeated local therapy offers potential for long-term survival in a carefully selected subset of patients with recurrent metastases.

Chronic kidney disease in the BCR-ABL1-negative myeloproliferative neoplasm: a single-center retrospective study

BACKGROUND/AIMS: Renal complications related to BCR-ABL1-negative myeloproliferative neoplasms (MPNs) have not been examined fully in Asian populations. METHODS: We analyzed estimated glomerular filtration rate (eGFR) and its changes with time retrospectively in patients with BCR-ABL1-negative MPN from 2005 to 2015. RESULTS: The prevalence of chronic kidney disease (CKD) was 11% (6.6% having stage 3 and 4.4% having stage 4). In a linear regression analysis of eGFR versus time (years), overall, patients showed increased eGFR (mL/min/1.73 m2) by 0.51 (95% confidence interval [CI], –0.30 to 1.33; p = 0.22). Patients with polycythemia vera (PV), and those treated with hydroxyurea, showed statistically significant increases in eGFR (1.59; 95% CI, 0.28 to 2.90; p = 0.22 in PV; and 1.55; 95% CI, 0.56 to 2.54; p = 0.22 in treatment with hydroxyurea). In total, 17 patients (20.5%) showed rapid loss of eGFR (7.0 × 109 /L) and high monocyte (> 0.7 × 109 /L) counts (76.5% vs. 50%, p=0.05; 52.9% vs. 28.8%, p= 0.06, respectively). More patients had high serum lactate dehydrogenase (> 500 U/L) levels (52.9% vs. 25.8%, p = 0.03) at diagnosis. CONCLUSIONS: CKD is prevalent in patients with BCR-ABL1-negative MPN. Active cytoreductive therapy has the potential to improve kidney function in BCR-ABL1-negative MPN.

Low-dose prednisolone in patients with paroxysmal nocturnal hemoglobinuria and inadequate response to eculizumab

No abstract available.

Dental Problems Related with Mastication and Swallowing / 대한연하장애학회지

Mastication and swallowing require the action of masticatory muscles, mandible, maxilla and teeth. Teeth play a significant role in pronunciation and aesthetics and form the occlusal surface, constituting the most important first step of the chewing function. In order for the tooth to withstand the masticatory function, the structure of the teeth must be strong, and the surrounding tissues such as the periodontal ligament and the alveolar bone should be maintained in a healthy state. The three major diseases of dentistry which are dental caries, periodontal disease and malocclusion: adversely affect the tooth and its surrounding tissues, and may cause masticatory and swallowing disorders. The purpose of this review is provide detailed information about dental problems and related mastication and swallowing problems.

The Survey about the Degree of Damage of Radiation-Protective Shields in Operation Room

BACKGROUND: Medical doctors who perform C-arm fluoroscopy-guided procedures are exposed to X-ray radiation. Therefore, radiation-protective shields are recommended to protect these doctors from radiation. For the past several years, these protective shields have sometimes been used without regular inspection. The aim of this study was to investigate the degree of damage to radiation-protective shields in the operating room. METHODS: This study investigated 98 radiation-protective shields in the operation rooms of Konkuk University Medical Center and Jeju National University Hospital. We examined whether these shields were damaged or not with the unaided eye and by fluoroscopy. RESULTS: There were seventy-one aprons and twenty-seven thyroid protectors in the two university hospitals. Fourteen aprons (19.7%) were damaged, whereas no thyroid protectors (0%) were. Of the twenty-six aprons, which have been used since 2005, eleven (42.3%) were damaged. Of the ten aprons, which have been used since 2008, none (0%) was damaged. Of the twenty-three aprons that have been used since 2009, two (8.7%) of them were damaged. Of the eight aprons used since 2010, one (12.3%) was damaged. Of the four aprons used since 2011, none (0%) of them were damaged. The most common site of damage to the radiation-protective shields was at the waist of the aprons (51%). CONCLUSIONS: As a result, aprons that have been used for a long period of time can have a higher risk of damage. Radiation-protective shields should be inspected regularly and exchanged for new products for the safety of medical workers.

A Randomized Controlled Trial about the Levels of Radiation Exposure Depends on the Use of Collimation C-arm Fluoroscopic-guided Medial Branch Block

BACKGROUND: C-arm fluoroscope has been widely used to promote more effective pain management; however, unwanted radiation exposure for operators is inevitable. We prospectively investigated the differences in radiation exposure related to collimation in Medial Branch Block (MBB). METHODS: This study was a randomized controlled trial of 62 MBBs at L3, 4 and 5. After the patient was laid in the prone position on the operating table, MBB was conducted and only AP projections of the fluoroscope were used. Based on a concealed random number table, MBB was performed with (collimation group) and without (control group) collimation. The data on the patient's age, height, gender, laterality (right/left), radiation absorbed dose (RAD), exposure time, distance from the center of the field to the operator, and effective dose (ED) at the side of the table and at the operator's chest were collected. The brightness of the fluoroscopic image was evaluated with histogram in Photoshop. RESULTS: There were no significant differences in age, height, weight, male to female ratio, laterality, time, distance and brightness of fluoroscopic image. The area of the fluoroscopic image with collimation was 67% of the conventional image. The RAD (29.9 +/- 13.0, P = 0.001) and the ED at the left chest of the operators (0.53 +/- 0.71, P = 0.042) and beside the table (5.69 +/- 4.6, P = 0.025) in collimation group were lower than that of the control group (44.6 +/- 19.0, 0.97 +/- 0.92, and 9.53 +/- 8.16), resepectively. CONCLUSIONS: Collimation reduced radiation exposure and maintained the image quality. Therefore, the proper use of collimation will be beneficial to both patients and operators.

Radiation Exposure of the Hand and Chest during C-arm Fluoroscopy-Guided Procedures

BACKGROUND: The C-arm fluoroscope is an essential tool for the intervention of pain. The aim of this study was to investigate the radiation exposure experienced by the hand and chest of pain physicians during C-arm fluoroscopy-guided procedures. METHODS: This is a prospective study about radiation exposure to physicians during transforaminal epidural steroid injection (TFESI) and medial branch block (MBB). Four pain physicians were involved in this study. Data about effective dose (ED) at each physician's right hand and left side of the chest, exposure time, radiation absorbed dose (RAD), and the distance from the center of the X-ray field to the physician during X-ray scanning were collected. RESULTS: Three hundred and fifteen cases were included for this study. Demographic data showed no significant differences among the physicians in the TFESIs and MBBs. In the TFESI group, there was a significant difference between the ED at the hand and chest in all the physicians. In physician A, B and C, the ED at the chest was more than the ED at the hand. The distance from the center of the X-ray field to physician A was more than that of the other physicians, and for the exposure time, the ED and RAD in physician A was less than that of the other physicians. In the MBB group, there was no difference in the ED at the hand and chest, except for physician D. The distance from the center of the X-ray field to physician A was more than that of the other physicians and the exposure time in physician A was less than that of the other physicians. CONCLUSIONS: In conclusion, the distance from the radiation source, position of the hand, experience and technique can correlate with the radiation dose.

Radiation Recall Dermatitis after Treatment with Paclitaxel and Cisplatin

No abstract available.

Long-term outcome of isolated thrombocytopenia accompanied by hypocellular marrow

BACKGROUND: Hypocellularity of bone marrow (BM), not associated with significant dyshematopoiesis, is often found in patients with isolated thrombocytopenia, but its clinical implications have not been studied. We prospectively studied the clinical features and natural history of these patients. METHODS: Adults with isolated thrombocytopenia (platelet counts 50x10(9)/L in 16 patients (80%). BM cellularity ranged from 5% to 25% (median, 15%) and was 150x10(9)/L) after 12, 56 and 66 months. Three patients developed pancytopenia after 11, 70 and 90 months. Two patients were consistent with moderate aplastic anemia, and 1 was confirmed as having refractory cytopenia with multilineage dysplasia. In the remainder of the patients, platelet counts remained unchanged. CONCLUSION: Isolated thrombocytopenia accompanied by hypocellular marrow encompasses a group of heterogeneous conditions.

Clinical features and outcomes of autoimmune hemolytic anemia: a retrospective analysis of 32 cases

BACKGROUND: There has been no report on the clinical features or natural history of autoimmune hemolytic anemia (AIHA) in the Korean adult population. This study retrospectively analyzed the clinical characteristics and long-term outcomes of AIHA in the Korean adults. METHODS: Patients newly diagnosed with AIHA between January 1994 and December 2010 at Chungnam National University Hospital were enrolled. Patient characteristics at diagnosis, response to treatment, and the natural course of the disease were documented. RESULTS: Thirty-two patients (31 females and 1 male) with a median age of 48 years (range, 17-86) were enrolled. Of these, 21.9% were initially diagnosed with secondary AIHA. Thirteen patients (40.6%) were initially diagnosed with Evans' syndrome. Of the 29 patients who were placed on therapy, 27 (93.1%) showed a partial response or better. Nevertheless, 1 year after initiating treatment, 80% of the patients were still treatment-dependent. During follow-up (median length 14 months; range, 0.5-238), 14 of 25 patients (56.0%) who were initially diagnosed with primary warm antibody AIHA were found to have systemic lupus erythematosus (SLE). Median time to conversion to SLE was 8.0 months (95% CI, 4.3-11.7), and the probabilities of conversion at 12 and 24 months were 63% and 91%, respectively. Younger age (<60 years) and a positive fluorescent anti-nuclear antibody test were associated with a higher probability of SLE conversion (P=0.01 and P<0.001, respectively). CONCLUSION: Primary AIHA is rare. Regular, vigilant testing for SLE is required in patients initially diagnosed with AIHA.

A Case of Multiple Solitary Plasmacytoma Recurring in Multiple Visceral Organs / 대한내과학회지

Multiple solitary plasmacytoma is a very rare disease entity, which occurs in up to 5% of patients with solitary plasmacytomas. We report an atypical case of multiple solitary plasmacytoma that recurred in multiple visceral organs without any evidence of bone marrow involvement. A 68-year-old male presented with voiding difficulty. Twenty months earlier, he had been placed on local radiotherapy for solitary plasmacytomas in the right 6th rib and right iliac bone. Recurrences were noted 14 and 12 months later in several ribs and the 5th cervical vertebra, respectively. These were well controlled with local radiotherapy and conventional systemic chemotherapy. He had multiple soft tissue masses in the stomach, pancreas, pelvic cavity, and right buttock. An endoscopic biopsy of the gastric mass confirmed the diagnosis of plasmacytoma. Local radiotherapy to the pelvic mass and systemic therapy consisting of bortezomib and dexamethasone were given, and he has been well for 8 months.

Clinical Implications of Elevated Antiphospholipid Antibodies in Adult Patients with Primary Immune Thrombocytopenia

BACKGROUND/AIMS: Antiphospholipid antibodies (aPL) have been detected in various proportions of patients with primary immune thrombocytopenia (ITP), but the clinical significance of this is debatable. The present study aimed to determine the frequency and clinical implications of elevated aPL in adult patients with ITP. METHODS: We prospectively studied newly diagnosed adult patients with ITP who were enrolled between January 2003 and December 2008 at Chungnam National University Hospital. They were evaluated for the presence of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) at diagnosis and were followed for the development of thrombosis. RESULTS: Seventy consecutive patients with ITP (median age, 48 years; range, 18 to 79) were enrolled. Twenty patients (28.5%) were positive for aPL at the time of diagnosis: aCL alone in 15 (75%), aCL and LA in two (10%), and LA alone in three (15%). Patients who had platelet counts < 50,000/microL were administered oral prednisolone with or without intravenous immune globulin. No difference was found between the aPL-positive and -negative groups regarding gender, initial platelet count, and response to the therapy. After a median follow-up of 20 months (range, 2 to 68), two of 20 patients who were aPL-positive (10%) developed thrombosis, whereas no thrombotic event was found among those who were aPL-negative. CONCLUSIONS: Our data suggest that aPL levels should be determined at the initial presentation of ITP and that patients found to be aPL-positive should receive closer follow-up for thrombotic events.

A Case of Multiple Myeloma Associated with Multifocal Osteosclerosis (Multiple Myeloma with Osteosclerosis)

Osteosclerotic myeloma is a rare entity, characterized by single or multiple osteosclerotic bone lesions and usually accompanied by a polyneuropathy syndrome (POEMS). Multiple myeloma with osteosclerotic lesions without polyneuropathy is exceedingly rare. We report a case of multiple myeloma associated with multifocal osteosclerotic lesions without any evidence of POEMS. A 48-year-old woman presented with incidentally found osteosclerosis of 8th thoracic vertebra on a plain chest film. Bone survey, CT scan, MR scan, and radioisotope scintigraphy revealed multiple localized osteoclerosis; serum protein immunofixation showed IgG, lambda monoclonal gammopathy. A biopsy of T8 vertebral body disclosed plasma cell myeloma. Given that there was no organ or tissue damage other than multifocal osteosclerosis, the patient was placed on close observation with regular examination. This case indicates that although rare, multiple myeloma should be included in the differential diagnosis of sclerotic bone lesions.

Anesthetic managements for correction of aortic valve regurgitation in a patient with Loeys-Dietz Syndrome: A case report / 대한마취과학회지

Loeys-Dietz Syndrome (LDS) is a recently described autosomal dominant aortic aneurysm syndrome with widespread systemic involvement. It is characterized by the triad of 1) arterial tortuosity and aneurysms, 2) hypertelorism, and 3) bifid uvula or cleft palate. A 12-year-old boy with LDS was scheduled to undergo correction of aortic valve regurgitation due to aortic annuloectasia. We report our clinical experiences of a case of LDS patient with brief review of related literatures and relevant anesthetic problems.

Clinical Assessment of Accommodative Esotropia

Accommodative esodeviation is the result of either the need to clear the blurred vision caused by hypermetropia or a high accommodative convergence to accommodation(AC/A) ratio. In 1958, Parks showed that there were three origins of accommodative convergence to accommodation(AC/A), and a combination of the two. The authors experienced 71 cases of accommodative esotropia which were treated with hyperopic glasses, executive bifocals, and surgery on nonaccommodative component. Accommodative esotropia was subdivided into 3 types as refractive, nonrefractive and combined type. The refractive type was 59.1%, nonrtfractive type 8.5%, and combined type 32.4%. Among all 71cases, partially accommodative esotropia was 32.4%. The onset was at the age between 2 and 4 years in 50.8%. In most cases the sphero-equivalent of refractive error was +4.00 to less than +6.00 D in the refractive type with a normal AC/A ratio, less than +2.00 D in the nonrefractive type with a high AC/A ratio, and +2.00 to less than +4.00 D in the combined type with a high AC/A ratio. The cases with a normal AC/A ratio showed more hypermetropia. The amount of esodeviation controlled by hyperopic glasses was 24.4 to 25.0 delta at distance; by executive bifocals 26.2 delta in the nonrefractive type and 18.6 delta in the combined type at near. Stereoacuity was tested in 34 cases who understood the test, was better in the refractive type with normal AC/A ratio than in nonrefractive and combined type with a high AC/A ratio, and was absent in 26.4%. In many cases without stereopsis, the interval between onset and institution of therapy was too long and the age at treatment was too old. The longer the eyes are not aligned the greater chance for the development of amblyopia and sensory motor misalignant. Therefore early recognition and early initiation of treatment should be emphasized.

The Correlation between Intraocular Pressure and Refractive Status

The tendency toward significantly higher mean tensions in myopic eyes compared with eyes with emmetropia and hyperopia has been believed. The patients with high myopia have an unusually high risk of the development of open angle glaucoma. But there is little information in the literature concerning the range of refractive error in relation to intraocular pressure. This study was designed to provide this information in Koreans and to assess the possible prognostic value of the refraction in glaucoma. The results of this study were as follows: 1. The mean IOP of all the patient were 15.29 +/- 2.61mmHg. 2. The mean IOP of emmetropic patients with +2.0 to -2.0 diopters, myopic patients with -2.25 to -4.75 diopters, and high myopic patients with greater than -5.0 diopters were each 14.99 +/- 2.62mmHg, 5.64 +/- 2.38mmHg, 16.21 +/- 2.56mmHg, respectively, suggesting that as the degree of myopia became higher, so did the IOP became greater, as supported by a statistical analysis showing significance(p0.01).

Two Cases of Cyclic Esotropia

Cyclic heterotropia represents an interesting ocular motility problem in which the ocular deviation is present on a rhythmic basis. Usually this appears in a regular 48-hour cycle, although 72-and 96-hour cycles have also been reported. On the strabismic day, constant heterotropia is large and associated with suppression and no diplopia. On the nonstrabismic day, no deviation or only a small heterophoria is present with good binocular function. In this paper, we present two cases of cyclic esotropia which demonstrated regular 48-hour cycles and were treated with surgery.