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.

Development of Metabolic Synthetic Lethality and Its Implications for Thyroid Cancer

Cancer therapies targeting genetic alterations are a topic of great interest in the field of thyroid cancer, which frequently harbors mutations in the RAS, RAF, and RET genes. Unfortunately, U.S. Food and Drug Administration-approved BRAF inhibitors have relatively low therapeutic efficacy against BRAF-mutant thyroid cancer; in addition, the cancer often acquires drug resistance, which prevents effective treatment. Recent advances in genomics and transcriptomics are leading to a more complete picture of the range of mutations, both driver and messenger, present in thyroid cancer. Furthermore, our understanding of cancer suggests that oncogenic mutations drive tumorigenesis and induce rewiring of cancer cell metabolism, which promotes survival of mutated cells. Synthetic lethality (SL) is a method of neutralizing mutated genes that were previously considered untargetable by traditional genotype-targeted treatments. Because these metabolic events are specific to cancer cells, we have the opportunity to develop new therapies that target tumor cells specifically without affecting healthy tissue. Here, we describe developments in metabolism-based cancer therapy, focusing on the concept of metabolic SL in thyroid cancer. Finally, we discuss the essential implications of metabolic reprogramming and its role in the future direction of SL for thyroid cancer.

Restrictive Strabismus Developing after Conjunctivodacryocystorhinostomy

Purpose@#To report a case of diplopia caused by restrictive strabismus developing after conjunctivodacryocystorhinostomy (CDCR).Case summary: A 61-year-old female presented with persistent epiphora after failure to repair ipsilateral canalicular lacerations of the left eye caused by trauma occurred 25 years ago. CDCR was performed and the epiphora improved. Four months later, the patient presented with diplopia on the left gaze. An abduction limitation of -4 and a supraduction limitation of -3 were observed in the left eye. Therefore, Jones tube removal was performed 5 months after CDCR surgery. Two weeks later, as the limitations persisted, adhesiolysis of the conjunctiva and an amniotic membrane transplantation (AMT) were performed. This exposed a subconjunctival adhesion at the inferonasal conjunctiva; histopathological examination revealed fibrotic tissues. Three months later, the adhesions recurred and the patient was transferred to another hospital. Conjunctival adhesiolysis, AMT, and a 6.5 mm recession of medial rectus (MR) muscle were performed. One week later, exotropia occurred in the primary position, and the MR muscle of the left eye was advanced by 2 mm. Nine months after the final surgery, the primary gaze was orthotropia. The diplopia within the central 20° of visual field had disappeared. However, a levoelevation limitation of -1.5 remained in the left eye. @*Conclusions@#CDCR is the only treatment method for patients with occlusion of both the upper and lower proximal lacrimal canaliculi. However, rare complications such as restrictive strabismus with diplopia may occur. As preventing adhesion is difficult, sufficient patient notice is required prior to surgery.

Expression of LONP1 Is High in Visceral Adipose Tissue in Obesity, and Is Associated with Glucose and Lipid Metabolism

Background@#The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPRmt) in adipose tissue is associated with obesity in humans and rodents. @*Methods@#Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data. @*Results@#In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression. @*Conclusion@#Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.

Expression of LONP1 Is High in Visceral Adipose Tissue in Obesity, and Is Associated with Glucose and Lipid Metabolism

Background@#The nature and role of the mitochondrial stress response in adipose tissue in relation to obesity are not yet known. To determine whether the mitochondrial unfolded protein response (UPRmt) in adipose tissue is associated with obesity in humans and rodents. @*Methods@#Visceral adipose tissue (VAT) was obtained from 48 normoglycemic women who underwent surgery. Expression levels of mRNA and proteins were measured for mitochondrial chaperones, intrinsic proteases, and components of electron-transport chains. Furthermore, we systematically analyzed metabolic phenotypes with a large panel of isogenic BXD inbred mouse strains and Genotype-Tissue Expression (GTEx) data. @*Results@#In VAT, expression of mitochondrial chaperones and intrinsic proteases localized in inner and outer mitochondrial membranes was not associated with body mass index (BMI), except for the Lon protease homolog, mitochondrial, and the corresponding gene LONP1, which showed high-level expression in the VAT of overweight or obese individuals. Expression of LONP1 in VAT positively correlated with BMI. Analysis of the GTEx database revealed that elevation of LONP1 expression is associated with enhancement of genes involved in glucose and lipid metabolism in VAT. Mice with higher Lonp1 expression in adipose tissue had better systemic glucose metabolism than mice with lower Lonp1 expression. @*Conclusion@#Expression of mitochondrial LONP1, which is involved in the mitochondrial quality control stress response, was elevated in the VAT of obese individuals. In a bioinformatics analysis, high LONP1 expression in VAT was associated with enhanced glucose and lipid metabolism.

Encapsulated Bleb Excision with Collagen Matrix Implantation Following Failed Ahmed Glaucoma Valve Implantation

PURPOSE: To investigate the clinical features and surgical outcomes of encapsulated bleb excision with collagen matrix implantation performed in patients with failed Ahmed glaucoma valve (AGV) implantation. METHODS: Eighteen eyes of 18 patients underwent encapsulated bleb excision and collagen matrix implantation. Patients were divided into two groups by reference to intraocular pressure (IOP) after preoperative ocular massage: group 1, patients who exhibited substantial IOP reductions; and group 2, patients who did not show substantial changes in IOP. Needling was conducted in group 2. The clinical features of the two groups were compared, including IOP changes after ocular massage and needling, AGV status, and surgical outcomes 6 months after surgery. RESULTS: The mean preoperative IOP among the 18 patients was 30.6 ± 5.7 mmHg. After ocular massage, the IOPs decreased by 22 and 26 mmHg in the two patients in group 1 and the 16 patients in group 2 showed a mean IOP reduction of 1.6 ± 2.2 mmHg (p = 0.013). IOPs decreased after needling in group 2 (range, 6 to 30 mmHg; p < 0.001). Fibrovascular tissue ingrowth into the AGV was observed in the two patients in group 1 and the same ingrowth was observed in 10 of the 16 patients in group 2. Six months after surgery the mean IOP among the 18 patients decreased significantly (19.1 ± 3.2 mmHg, p < 0.001). There was no significant difference in the mean postoperative IOP at 6 months between group 1 (14.0 ± 2.8 mmHg) and group 2 (19.8 ± 2.6 mmHg, p = 0.052). CONCLUSIONS: Encapsulated bleb excision with collagen matrix implantation resulted in a significant IOP-lowering effect 6 months after surgery. Fibrovascular ingrowth into the AGV was common but did not seem to be a major cause of AGV implantation failure.

Effects of Long-Term Subcultured Arbuscular Mycorrhizal Fungi on Red Pepper Plant Growth and Soil Glomalin Content

Arbuscular mycorrhizal fungi (AMF) are well-known for their ability to improve plant growth and help plants withstand abiotic stress conditions. Unlike other fungi and bacteria, AMF cannot be stored, as they are obligate biotrophs. Long-term preservation of AMF spores is challenging and may lead to the loss of viability and efficiency. This study aimed to understand the effect of prolonged subculture of AMF species on the growth and glomalin-related soil protein (GRSP) from red pepper (Capsicum annuum L.). AMF spores were mass-produced using different techniques and subcultured in pots with sorghum sudangrass as the host plant for 3 years. Experimental soil samples were collected from natural grassland. Five different AMF inocula were used in triplicate as treatments. After 70 days of growth, red pepper plants were harvested and plant dry weight, plant nutrient content, mycorrhizal colonization, AMF spore count, and soil glomalin content were determined. AMF-treated plants displayed higher dry weight than controls, with only fruit dry weight being significantly different. Similarly, significant differences in phosphorous and potassium contents of the above-ground plant parts were observed between mycorrhizal and control treatments. In addition, soil GRSP content was significantly higher in plants inoculated with Rhizophagus sp. and Gigaspora margarita. The increased plant growth and GRSP content suggest that AMF can be maintained for 3 years without losing their efficiency if subcultured regularly with different symbiotic host plants.

Parry-Romberg Syndrome Associated with Hypothyroidism

PURPOSE: We report a case of Parry-Romberg syndrome associated with right enophthalmos, hypotropia, up-gaze limitation, en coup the sabre, morphea, and hypothyroidism. CASE SUMMARY: A 41-year-old woman presented with slowly progressive right enophthalmos that started 5 years previous. With a Hertel exophthalmometer, the right eye measured 10 mm, and the left eye 13 mm. Right enophthalmos and atrophy of subcutaneous tissues of right side orbit were observed. Axial scan of computerized tomography shows atrophy of right side orbital subcutaneous tissues without bony abnormality. At primary gaze, 4 prism diopter hypotropia was observed in the right eye. Up-gaze was limited in both eyes. Visual acuity was 1.0 in both eyes. No specific sign was found in her anterior segment. The patient had experienced right side alopecia 20 years prior and had undergone biopsy, which proved morphea. Linear en coup de sabre morphea was found on the right forehead and scalp. Hypothyroidism due to Hashimoto's thyroiditis was diagnosed based on a blood test, which also showed positive antinuclear antibody. Thus, the patient was diagnosed with Parry-Romberg syndrome associated with hypothyroidism. CONCLUSIONS: Clinicians need to consider the rare disease Parry-Romberg syndrome when a patient with ophthalmologic symptoms such as enopthlamos or eye movement disorders is accompanied by dermatologic symptoms such as linear en coup de sabre morphea or alopecia.

NAD(P)H: Quinone Oxidoreductase 1 and NRH:Quinone Oxidoreductase 2 Polymorphisms in Papillary Thyroid Microcarcinoma: Correlation with Phenotype

PURPOSE: NAD(P)H:Quinone Oxidoreductase 1 (NQO1) C609T missense variant (NQO1*2) and 29 basepair (bp)-insertion/deletion (I29/D) polymorphism of the NRH:Quinone Oxidoreductase 2 (NQO2) gene promoter have been proposed as predictive and prognostic factors for cancer development and progression. The purpose of this study is to investigate the relationship between NQO1/NQO2 genotype and clinico-pathological features of papillary thyroid microcarcinoma (PTMC). MATERIALS AND METHODS: Genomic DNA was isolated from 243 patients; and clinical data were retrospectively analyzed. NQO1*2 and tri-allelic polymorphism of NQO2 were investigated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: PTMC with NQO1*2 frequently exhibited extra-thyroidal extension as compared to PTMC with wild-type NQO1 (p=0.039). There was a significant relationship between I29/I29 homozygosity of NQO2 and lymph node metastasis (p=0.042). Multivariate analysis showed that the I29/I29 genotype was associated with an increased risk of lymph node metastasis (OR, 2.24; 95% CI, 1.10-4.56; p=0.026). CONCLUSION: NQO1*2 and I29 allele of the NQO2 are associated with aggressive clinical phenotypes of PTMC, and the I29 allele represents a putative prognostic marker for PTMC.

A Case of Cytomegalovirus Colitis with Nontuberculous Mycobacterium Infection in Immunocompetent Host

Cytomegalovirus(CMV) infections are common in immune compromised situations such as human immunodeficiency virus infection and organ transplantation. However CMV colitis had been rarely found in immunocompetent individuals. We experienced a case of an 83-year-old female patient, initially immune competent, who developed a massive lower gastrointestinal bleeding caused by CMV colitis. Previously, multiple antibiotics were used for nontuberculous Myco- bacterium and other bacterial infections after total knee arthroplasty. Colonoscopy revealed multiple ulcerations and mucosal congestion with hemorrhage. In spite of ganciclovir therapy, our patient did not recover.

The Prevalence of Gastroesophageal Reflux Disease Associated with Age and Body Mass Index in Healthy Koreans

BACKGROUND: The prevalence of obesity is increasing year after year in Korean; and gastroesophageal reflux disease(GERD) is increasing in this population as well. The aim of this study is to assess the association between age, body mass index(BMI) and GERD in healthy Korean adults. METHODS: Analysis was done on 1,016 subjects who had not had malignancy, uncontrolled metabolic disease, enteric surgery and organic esophageal disease. They completed a questionnaire that included past history and reflux symptoms. Endoscopy was performed by two gastroenterologists who were not given any patient information. Existence of GERD was determined by the esophageal syndrome criteria of the Montreal guidelines. Subjects were categorized by BMI, initially as: underweight, normal(18.5 or =25) group(12.1%) showed a meaningful increment in the prevalence of erosive GERD compared to the non-obese(BMI<25) group(6.2%)(p value 0.002). CONCLUSION: The prevalence of GERD in healthy Korean adult subjects was not closely associated with obesity and age[according to BMI]; however, erosive GERD was found to have a strong association with obesity.

A Case of Pancreaticobiliary Duct Obstruction due to Pancreatic Tuberculosis Combined with a Colon Adenocarcinoma and Tuberculous Colitis / 대한소화기내시경학회지

Systemic manifestation of tuberculosis is common, but tuberculous biliary obstruction of the pancreas and a colon adenocarcinoma with combined colonic tuberculosis is an uncommon disorder. We encountered a case of the above condition in 63-year-old male that was admitted to our hospital because of fever, diffuse abdominal pain and rigidity. Abdominal computed tomography showed biliary and pancreatic duct dilatation with left colonic wall thickening and surrounding peritoneal infiltration. Emergency segmental resection of the descending colon with intraoperative T-tube choledochostomy was performed due to the colon mass and biliary obstruction. A colonofiberoscopy was performed for low abdominal pain and hematochezia at 12 days after surgery. It showed multiple colonic ulcerations with a partial stricture. A colonic biopsy showed granulomatous inflammation with acid-fast bacilli. The cause of the biliary obstruction was also revealed as pancreatic tuberculosis by an intraoperative pancreatic and mesenteric biopsy. The patient improved after antituberculous treatment and the patient has been in good health until the last outpatient follow-up visit.

A Case of Kaposi Sarcoma of the Bronchi and Gastrointestinal Tract in an AIDS Patient

Kaposi sarcoma is a rare tumor originated from skin in patients with immune suppressive illness like as acquired immunodeficiency syndrome (AIDS) or organ transplantation. It may be widely disseminated internally such as digestive or respiratory organ. In Korean patients with AIDS, Kaposi sarcoma is rarely seen rather than western countries. The reason is unknown. Although few cases of Kaposi sarcoma in patients with AIDS had been described in the Korean literatures, multi-organ involved cases were extremely rare. We describe a case of old AIDS patient in whom Kaposi sarcoma had affected multi-organs including esophagus, stomach, duodenum, colon, bronchi and skin.

2 Cases of Huge Bezoar in Geriatric Patients that Endoscopically Removed Through Direct Injection of Coca-Cola

In case of bezoar removal, pharmacotherapy has been performed within restrictive patients as well as therapeutic endoscopy has been restricted as to the size of bezoar and its hardness. In patients with huge and hard bezoars, that is unable to remove through endoscopy they need surgical removal. But in case of geriatric patient management, we can't overlook the complication of general anethesia and post operative wound infection. Thus we describe two case of geriatric patient that endoscopically removed bezoar through the medium of dissolved by Coca-Cola direct injection and lavage. We injected Coca-Cola directly to bezoar through the spray catheter and then Coca-Cola lavage daily two liters for three days. We could easily destroy dissolved huge bezoars by using of biopsy forcep and snare and than get rid of them endoscopically by use of basket. In case of geriatric patient management of huge gastric bezoar it is considered another choice for bezoar removal.

A Case of Spontaneous Uterine Rupture in the Second Trimester of Pregnancy

Uterine rupture in the second trimester is rare, but it is a surgical emergency. Also it results rapid deterioration of patient and high mortality despite of prompt therapy and massive transfusion. Radiologic studies often do not allow definitive diagnosis of it, so clinical judgement is critical for optimizing patient care. We present a case of spontaneous uterine rupture with fetal death in 17 weeks of pregnancy due to placenta percreta with brief review of the literature.

Clinical Analysis of Malarial Infections between January and September 1998 / 대한내과학회지

OBJECTIVE: Annually, the prevalence of indigenous and imported malarial infections is steadily increasing since 1993 in Korea. In order to understand the current characteristics of malarial infections and to prevent, the present research reviewed twenty-seven cases between January and September 1998. METHOD:In this study, all the twenty-seven (twenty- six patients) cases were obtained from admitted patients between January and September 1998. We had performed routine blood chemical studies, peripheral blood thin and thick smear, physical examination and abdominal sonography. Any patient with a previous history of a narcotic drug injection or had blood transfusion was excluded. RESULTS: Twenty cases (74.1%) were indigenous and seven (25.9%) were imported malaria. Yeonchon-Gun (nine cases) was the most prevalent area in the indigenous cases; Cambodia (three cases) were the most one in the imported cases. Peripheral blood thin smear revealed Plasmodium vivax in all (100%) indigenous malaria, while four cases (57.1%) were P. vivax and one (14.3%) was P. falciparum and two (28.6%) were mixed infections with P. vivax and P. falciparum in the imported cases. In a 3-month period between July and September, peak prevalence (80.4%) was observed. The negative conversion of peripheral blood smear was achieved much earlier in the indigenous (3.9+/-1.4day) than in the imported (5.7+/-1.9day) after the treatment but, was not statistically signifcant. CONCLUSION: Plasmodium ovale was the only unique causative species in the indigenous malaria. Also Yeonchon-Gun and Cheolwon-Gun had been the most important endemic areas as previous reports. One relapse case had been occurred in the imported malaria. On the basis of our data, more efforts for control of malaria should be necessary for eradication and prevention of indigenous and imported malarial infections in Korea.

Lipoid Pneumonia After Aspiration of Squalene(R) in Rabbit / 결핵

No abstract available.

A Case of Pneumocystis Carinii Pneumonia with Histopathologic Finding of Bronchiolitis Obliterans with Organizing Pneumonia in Patient with AIDS / 결핵

PCP remains the leading cause of deaths in patients with AIDS. As familiarity with PCP increases, atypical manifestations of the diseases are being recognized with greater frequency. There are following "atypical" manifestations of PCP; 1) interstitial lung response that include diffuse alveolar damage, bronchiolitis obliterance, interstitial fibrosis, and lymphoplasmocytic infiltrate 2) striking localized process frequently exhibiting granulomatous features 3) extensive necrosis & cavitation 4) extrapulmonary dissemination of the disease. A wide variety of pathologic manifestations may occur in PCP in human immunodeficiency virus- infected patienst and that atypical features should be sought in lung biopsies from patients at risk for PCP. We had experienced a case of PCP, which presented with severe hypoxia, progressive dyspnea and fine crackles. It was diagnosed as PCP in AIDS with manifestation of BOOP by open lung biopsy and showed good response to Bactrim & corticosteroid therapy.

Effect of Erythropoietin on Dialyzer Reuse, Dialysis Efficacy and Other Clinical Parameters / 대한신장학회잡지

The use of erythropoietin for correction of anemia in maintenance hemodialysis patients affects dialyzer reuse, dialysis efficacy and other clinical parameters. This study showed the change of Kt/Vurea, nPCR, pre-dialysis BUN, body weight, ultrafiltration volume, pre-dialysis blood pressure, heparin dosage, the number of dialyzer reuse caused by the administration of erythropoietin in reuse(n=11) and first use(n=9) patients who were started erythropoietin since January, 1995. 1) In 20 all patients, hematocrit increased significantly after EPO treatment 20.7+/-0.8%, 27.8+/-0.7%, ultrafiltration volume increased from 2.0+/-0.3L to 2.5+/-0.2L(P1.0/kg/ day) and then pretreatment versus posttreatment nPCR, pre-dialysis BUN and ultrafiltration volume were compared. In low baseline protein intake group, significant increases of ultrafiltration volume, nPCR were observed. However, pre-dialysis BUN were not changed significantly. In high protein intake group, nPCR, pre-dialysis BUN, ultrafiltration volume were changed without significance. In conclusion, EPO treatment did not affect Kt/Vurea, dialyzer reuse, nPCR, predialysis blood pressure, heparin dosage. But ultrafiltration volume increased significantly after EPO treatment. Maybe increased appetite in low baseline protein intake group caused the increased posttreatment ultrafiltration volume.