Autophagy is a conserved catabolic process that degrades proteins and damaged organelles to maintain cellular homeostasis, and its role in cancer depends on stage and context. Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is an essential enzyme in the sterol branch of the mevalonate pathway, but its functions in hepatocellular carcinoma (HCC) and in the regulation of autophagy remain poorly understood. In this study, we show that FDFT1 acts as a negative regulator of autophagy in HCC cells. Loss of FDFT1 led to increased autophagosome formation and fusion with lysosomes, whereas its overexpression suppressed both basal and induced autophagy. These changes were associated with AMPK–ULK1 signaling, suggesting that FDFT1 influences a central pathway controlling autophagy. Our findings connect cholesterol metabolism with autophagy regulation and tumor growth, highlighting FDFT1 as a potential prognostic marker and therapeutic target in liver cancer.

A 55-year-old woman with stage IV follicular lymphoma developed progressive multifocal leukoencephalopathy (PML) during rituximab maintenance therapy following bendamustine-rituximab induction. Although pembrolizumab administration was initiated for suspected PML, her neurological status deteriorated, ultimately leading to death. This case highlights the limited therapeutic response to pembrolizumab in profoundly immunocompromised patients, highlighting the need for timely diagnosis, immunovirological assessment, and individualized innovative management approaches for PML.

PURPOSE: The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS). RESULTS: At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170). CONCLUSION: A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.
Cohort Studies ; Disease-Free Survival ; Education ; Follow-Up Studies ; Humans ; Nasopharyngeal Neoplasms ; Radiotherapy ; Radiotherapy, Intensity-Modulated ; Retrospective Studies* ; Treatment Outcome

PURPOSE: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea. METHODS: A total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs. RESULTS: Carbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs (P< 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs (P= 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P= 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS. CONCLUSION: This was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.
Anticonvulsants ; Carbamazepine ; Cicatrix ; Drug Hypersensitivity Syndrome ; Epidemiologic Studies ; Hospitalization ; Humans ; Incidence ; Korea ; Length of Stay ; Mortality ; Referral and Consultation ; Risk Factors ; Stevens-Johnson Syndrome ; Thrombocytopenia ; Valproic Acid

PURPOSE: There was a global increase in the prevalence of oseltamivir-resistant influenza viruses during the 2007-2008 influenza season. This study was conducted to investigate the occurrence and characteristics of oseltamivir-resistant influenza viruses during the 2007-2008 and 2008-2009 influenza seasons among patients who were treated with oseltamivir (group A) and those that did not receive oseltamivir (group B). METHODS: A prospective study was conducted on 321 pediatric patients who were hospitalized because of influenza during the 2007-2008 and 2008-2009 influenza seasons. Drug resistance tests were conducted on influenza viruses isolated from 91 patients. RESULTS: There was no significant difference between the clinical characteristics of groups A and B during both seasons. Influenza A/H1N1, isolated from both groups A and B during the 2007-2008 and 2008-2009 periods, was not resistant to zanamivir. However, phenotypic analysis of the virus revealed a high oseltamivir IC50 range and that H275Y substitution of the neuraminidase (NA) gene and partial variation of the hemagglutinin (HA) gene did not affect its antigenicity to the HA vaccine even though group A had a shorter hospitalization duration and fewer lower respiratory tract complications than group B. In addition, there was no significant difference in the clinical manifestations between oseltamivir-susceptible and oseltamivir-resistant strains of influenza A/H1N1. CONCLUSION: Establishment of guidelines to efficiently treat influenza with oseltamivir, a commonly used drug for treating influenza in Korean pediatric patients, and a treatment strategy with a new therapeutic agent is required.
Child ; Drug Resistance ; Hemagglutinins ; Hospitalization ; Humans ; Influenza, Human ; Inhibitory Concentration 50 ; Neuraminidase ; Orthomyxoviridae ; Oseltamivir ; Prevalence ; Prospective Studies ; Respiratory System ; Seasons ; Viruses ; Zanamivir

BACKGROUND: Introduction of automation instruments for the blood bank is essential in order to reduce inspection error and minimize workload. We compared the results of ABO-RhD blood type and antibody screening tests using the manual method and those using the automation instruments AutoVue Innova (Ortho-Clinical Diagnostics, Raritan, NJ, USA) and QWALYS-3 (DIAGAST, Loos Cedex, France). METHODS: ABO-RhD blood type tests using the slide method, the tube method, and the instruments were performed with 200 selected samples. Antibody screening tests using the Ortho BioVue system (Ortho-Clinical Diagnostics, Raritan, NJ, USA), which is used in our laboratory, and the two instruments were performed with 188 specimens and 12 antibody positive samples that were kept in the laboratory. We evaluated the concordance rate of the results, applying CLSI guideline EP12-A2. RESULTS: The concordance rate of ABO-RhD blood type results between the manual methods and the two instruments was 100%. On antibody screening tests, a concordance rate of 100% was observed between the manual method and AutoVue Innova, which uses the gel card manufactured by the company making the gel card used for the manual method. However, using QWALYS-3 in performance of antibody screening tests, the concordance rate was 97.5%, because of discordance in five specimens. CONCLUSION: The concordance rate of ABO-RhD blood type by use of two automation instruments was 100%, however, that of the antibody screening test was 97.5%. Thus, there was a difference in positive rate on the antibody screening test, depending on the instrument. Therefore, introduction of an instrument, considering the pros and cons for each instrument, is necessary. In addition, further discussion of standardized guidelines for quality control is needed.
Automation ; Blood Banks ; Cephalosporins ; Mass Screening ; Quality Control

Follicular dendritic cell sarcoma (FDCS) is a rare malignancy arising from the antigen-presenting cells in the lymph node and extranodal tissue. We describe a 31-year-old male patient who presented with a swelling of the left parapharynx. The radiologic findings showed a 4.7x4.5x1.9 cm-sized, ill-defined mass in the left parapharyngeal space. A fine-needle aspiration cytology was performed and it showed scattered, irregular, cohesive clusters of tumor cells with a spindle-to-ovoid shape with irregular contours in a background of lymphocytes. Based on these findings, a diagnosis of spindle cell neoplasm was made. The surgically resected tumor was composed of elongated, ovoid or polygonal cells showing positive immunohistochemistry for CD21, CD23, and CD35. Postoperatively, the residual tumor was observed to undergo a rapidly growth. There is an overlap in the cytologic and histologic findings between FDCS of the parapharynx and other tumors. Pathologists should therefore be aware of its characteristics not only to provide an accurate diagnosis but also to recommend the appropriate clinical management.
Male ; Humans

Follicular dendritic cell sarcoma (FDCS) is a rare malignancy arising from the antigen-presenting cells in the lymph node and extranodal tissue. We describe a 31-year-old male patient who presented with a swelling of the left parapharynx. The radiologic findings showed a 4.7x4.5x1.9 cm-sized, ill-defined mass in the left parapharyngeal space. A fine-needle aspiration cytology was performed and it showed scattered, irregular, cohesive clusters of tumor cells with a spindle-to-ovoid shape with irregular contours in a background of lymphocytes. Based on these findings, a diagnosis of spindle cell neoplasm was made. The surgically resected tumor was composed of elongated, ovoid or polygonal cells showing positive immunohistochemistry for CD21, CD23, and CD35. Postoperatively, the residual tumor was observed to undergo a rapidly growth. There is an overlap in the cytologic and histologic findings between FDCS of the parapharynx and other tumors. Pathologists should therefore be aware of its characteristics not only to provide an accurate diagnosis but also to recommend the appropriate clinical management.
Male ; Humans

Osteopetrosis is a rare bone disease characterized by systemic osteosclerosis due to an osteoclast dysfunction that decreases bone resorption. This report demonstrates two cases of adult osteopetrosis with secondary osteomyelitis of the maxilla, in siblings who are 43-year old female and 55-year old, male respectively. The common radiographic features of these cases were increased radiopacity in skull, rib and vertebra. The radiographic features that differed between these two cases were the osteosclerotic pattern of the jaw bones, that is, diffuse patterns in the female case, while the male case showed nodular patterns that were confined to the root apices. The diagnosis of osteopetrosis may be complicated due to the varying degree of osteosclerosis on panoramic radiograph. Additional radiographs such as the chest and skull radiograph may be helpful for the diagnosis of osteopetrosis.
Adult ; Bone Diseases ; Bone Resorption ; Female ; Humans ; Jaw ; Male ; Maxilla ; Osteoclasts ; Osteomyelitis ; Osteopetrosis ; Osteosclerosis ; Radiography, Panoramic ; Ribs ; Siblings ; Skull ; Spine ; Thorax

BACKGROUND: The aim of this study was to evaluate differences in cytologic findings between conventional preparation (CP) and SurePath(TM) liquid-based preparation (LBP) in thyroid fine needle aspiration (FNA). METHODS: We analyzed cytological features on a total of 182 thyroid FNAs (83 CP and 99 LBP) that were histologically confirmed as nodular hyperplasia (NH) or papillary carcinoma (PAC). RESULTS: LBP was superior in cellular preservation and cellularity than CP. Interestingly, in LBP, cellularity of NH was similarly high compared to that of PAC. The three-dimensional pattern was more prominent in LBP than in CP. The presence of follicle structures was more frequently found in LBP than in CP in the PAC group. Dispersed single cells in the background were more prominent in LBP than in CP. In the PAC group, contrast of the nuclear membrane was more distinctive in CP than in LBP. CONCLUSIONS: In thyroid FNA, LBP is better for cellular preservation, cellularity, background and nuclear detail than CP. However, some features in LBP such as high cellularity in NH, prominent dispersed single cells, and frequent follicle patterns were unfamiliar findings in CP. Hence, we should be aware of these cytomorphologic features in LBP to make a proper diagnosis.
Biopsy, Fine-Needle ; Carcinoma, Papillary ; Hyperplasia ; Nuclear Envelope ; Thyroid Gland