Two Cases of Lymph Node Metastasis Found in Differentiated, Small-Sized Gastric Adenocarcinomas: Did Tumor Budding Play a Critical Role?

Background: Endoscopic resection (ER) is a minimally invasive therapeutic approach for early gastric cancer (EGC), particularly for cases with a low risk of lymph node metastasis (LNM). Tumor budding (TB) has gained attention as a potential prognostic indicator for LNM in EGC. Case Presentation: We report two cases-a 73-year-old and an 81-year-old male patient-who presented with gastric adenocarcinoma. Both patients had small-sized, differentiated, and intramucosal adenocarcinomas. However, high-grade TBs per high-power field under ×200 magnification at the invasive front and LNMs were found in both cases. Conclusions: These cases conformed to the post-ER observation guidelines of the current treatment protocol, yet demonstrated LNMs. We found that TB could serve as an effective prognostic marker for LNM compared to traditional risk factors. The aim of this study is to re-examine the ability of TB to predict LNM in EGC, thereby providing an impetus for reconsideration and potential revision of the current treatment guidelines for EGC.

High Expression of NRF2 and Low Expression of KEAP1 Predict Worse Survival in Patients With Operable Triple-Negative Breast Cancer.

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer. Currently, no effective treatment options for this condition exist. Nuclear factor erythroid 2-related factor 2 (NRF2), encoded by nuclear factor erythroid-derived 2-like 2 (NFE2L2) gene and its endogenous inhibitor, Kelch-like ECH-associated protein 1 (KEAP1), both participate in cellular defense mechanisms against oxidative stress and contribute to chemoresistance and tumor progression in numerous types of cancers. This study aimed to evaluate the expression patterns of NRF2 and KEAP1 and their prognostic value in operable TNBC. METHODS: Tissue microarrays were prepared using tumor tissues collected from 203 patients with TNBC who underwent surgery. Immunohistochemical staining analyses of NRF2 and KEAP1 were performed. The expression of each immunomarker was categorized into two groups (low or high) based on the median H-score. We analyzed the association between the expression of each immunomarker and clinicopathological information to predict survival. A total of 225 TNBC samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset were used to validate our results. RESULTS: NRF2 immunoreactivity was detected in the nucleus and was associated with histologic grade and Ki-67 index, whereas KEAP1 immunoreactivity was detected in the cytoplasm and was associated with the Ki-67 index. Survival analyses showed that NRF2 and KEAP1 expressions were independent prognostic factors for overall survival (OS) (hazard ratio [HR], 2.45 and 0.30; p = 0.015 and 0.016, respectively) and disease-free survival (HR, 2.27 and 0.42; p = 0.019 and 0.022, respectively). NFE2L2 mRNA expression was an independent prognostic factor for OS (HR, 0.59; p = 0.009) in the METABRIC dataset. CONCLUSION: High NRF2 and low KEAP1 expressions independently predicted poor survival in patients with operable TNBC. Further investigations are warranted to examine the possible therapeutic benefits of targeting the KEAP1-NRF2 pathway for TNBC treatment.

Granulomatous gastritis induced by chronic peanut ingestion.

Granulomatous gastritis (GG) is a rare condition, with incidence between 0.08 and 0.35% in gastric biopsies. Various infectious and non-infectious aetiologies can be considered to cause granulomatous gastritis. Foreign bodies are a rare aetiology of GG and may result from foods, suture materials, or medications. We report a 59-year-old woman who had eaten large amounts of peanuts for more than 10 years and presented with epigastric discomfort. Esophagogastroduodenoscopy revealed multiple nodular lesions with ulcer scars at the stomach, which was diagnosed as GG probably caused by chronic peanut ingestion on endoscopic mucosal resection.

Magnetic resonance fingerprinting in prostate cancer before and after contrast enhancement.

OBJECTIVES: To assess the apparent diffusion coefficient (ADC) values and the T1 and T2 values derived from nonenhanced (NE) and contrast-enhanced (CE) magnetic resonance fingerprinting (MRF) in the prostate gland and to evaluate differences in values among prostate cancer, the normal peripheral zone (PZ) and the normal transition zone (TZ). METHODS: Fifty-seven patients (median age, 73 years; range, 48-86) with prostate cancer who underwent multiparametric MRI including NE and CE MRF were included in this study. T1 and T2 values were extracted from NE and CE MRF, respectively. Five quantitative values (the ADC, NE T1, NE T2, CE T1 and CE T2 values) were measured in three areas: prostate cancer, PZ and TZ. We compared the values among the three areas and evaluated the differences between NE MRF and CE MRF values. RESULTS: ADC values and MRF-derived values were significantly higher in PZ than prostate cancer or TZ (p < 0.001). TZ had a significantly lower CE T1 but significantly higher values of the other variables than prostate cancer (p < 0.001). The T1 values in all three areas and the T2 values in prostate cancer and TZ were significantly lower on CE MRF than on NE MRF (p < 0.001). CONCLUSIONS: Quantitative analysis of NE and CE MRI can be conducted by using the MRF technique. The ADC value and the T1 and T2 values from CE MRF and NE MRF were found to be significantly different between prostate cancer and normal prostate tissue. ADVANCES IN KNOWLEDGE: The T1 and T2 values from contrast-enhanced MR fingerprinting are significantly different between prostate cancer and normal prostate tissue.

How Much Reliable Is the Current Belief on Grade Group 1 Prostate Cancer?

Objective: To evaluate the clinicopathological characteristics of grade group 1 (GG1) prostate cancer in Korean populations. Methods: We retrospectively analyzed 492 consecutive radical prostatectomy specimens from our institution, which included those from 322 men with clinical GG1 and 170 with clinical GG2 tumors between years 2009 and 2018. The incidence of Gleason score (GS) upgrading, extraprostatic extension (EPE), and seminal vesicle invasion (SVI) were evaluated in patients with clinical GG1. In pathological GG1 cases, the distribution of adverse pathological features including EPE, lymphovascular invasion (LVI), perineural invasion (PNI), and biochemical recurrence (BCR) was analyzed. Results: Altogether, 78 (24.2%) out of 322 men in the clinical GG1 group demonstrated upgrading of GS, including 19 men with pathological Gleason score 4 + 3 = 7 and 6 with ≥ pathological Gleason score 4 + 4 = 8 cases. EPE was found in 37 (11.5%) and 22 (8.9%) men in clinical GG1 and pathological GG1 group, respectively. The incidence of LVI and PNI in the pathological GG1 cases was 2.8% (n = 7) and 28.6% (n = 71), respectively. BCR was observed in 4 men in pathological GG1 T2 (n = 226) and 2 men in GG1 T3 (n = 22) group. When we compared the pathological features between pathological GG1 T3 vs. GG2 T2, there was no statistical differences in the incidence of LVI and PNI between the two groups. Conclusions: Contrary to the current concept that GG1 is almost always clinically insignificant, it seems that GG1 still possess its respectable position as a group of cancer with aggressiveness. These findings should be kept in mind when deciding on treatment options for prostate cancer patients in the Asian populations.

The Effectiveness of Hyperbaric Oxygen Therapy in Severe Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: To evaluate the effect of combined hyperbaric oxygen therapy (HBOT) and steroid therapy in severe idiopathic sudden sensorineural hearing loss (ISSNHL). METHODS: Between January 2010 and July 2017, we evaluated 218 patients with ISSNHL and divided them into 2 groups: those with hearing loss greater than 80 dB and those with hearing loss of 60-79 dB. Each group was further divided into 3 groups according to the treatment method: oral steroids alone (PO), PO+intratympanic injection (IT), and PO+IT+HBOT. The treatment effect was evaluated for improvement in hearing thresholds at mid-term (3 weeks later) and final term (2 months later). RESULTS: When comparing the 3 treatment groups within the group that had a hearing loss greater than 80 dB, no differences were observed in the gaps in hearing thresholds and in the duration of improvement (P = .0764 and .2938, respectively). However, in the group with 60-79 dB hearing loss, the gaps in hearing thresholds at mid-term were 27.50 dB in the PO group, 38.13 dB in the PO+IT group, and 51.25 dB in the PO+IT+HBOT group. The treatment was more effective and faster in the initial period in the PO+IT+HBOT group than in the other groups. In addition, the results of frequency analysis showed greatest treatment efficacy at low frequencies of hearing. CONCLUSION: Patients with ISSNHL above 80 dB are less likely to recover hearing even after PO+IT+HBOT. However, this treatment initially accelerates recovery in patients with a hearing loss below 80 dB. Therefore, the appropriate indication for HBOT benefits in patients with severe or profound ISSNHL should be reviewed.

Epithelial-myoepithelial carcinoma originating from a minor salivary gland in the nasal septum: A case report and literature review.

RATIONALE: Epithelial-myoepithelial carcinoma is an extremely rare, malignant neoplasm that occurs most frequently in the major salivary glands and accounts for approximately 1% of all salivary gland neoplasms. Few reports have described the presence of epithelial-myoepithelial carcinoma in the sinonasal region; hence, the treatment guideline and prognosis remain unclear. PATIENT CONCERNS: We reported a case of a 75-year-old woman with complaint of nasal obstruction and frequent epistaxis for 3 years. During the nasal endoscopic examination, a mass in the left nasal cavity originating from the left nasal septum that caused bleeding on touch was observed. DIAGNOSES: A diagnosis of epithelial-myoepithelial carcinoma was made based on the features of histopathology and immunohistochemistry of the surgical specimens. The patient was treated by surgical removal of the septal mass using the endonasal endoscopic approach. OUTCOMES: In the serial follow-up paranasal sinus imaging and endoscopic inspection, evidence of recurrence was absent for 18 months after surgery. LESSONS: This report highlights a case of epithelial-myoepithelial carcinoma originating from a minor salivary gland in the nasal septum, one of the most unusual locations. Diagnosis of epithelial-myoepithelial carcinoma should be made based on the findings of immunohistochemistry of the operative specimen. Clinicians should consider complete surgical resection as the effective treatment of choice.

Improved Quantification of 18F-FDG PET during 131I-Rituximab Therapy on Mouse Lymphoma Models after 131I Prompt Emission Correction.

18F-FDG Positron Emission Tomography (PET) is used to monitor tumor response to 131I-therapy, but is confounded by prompt emissions (284, 364, 637, and 723 keV) from 131I, particularly in animal PET imaging. We propose a method for correcting this emission in 18F-FDG PET. The 131I prompt emission effect was assessed within various energy windows and various activities. We applied a single gamma correction method to a phantom and in vivo mouse model. The 131I prompt emission fraction was 12% when 300 µCi of 131I and 100 µCi of FDG were administered, and increased exponentially with escalating 131I activity for all energy windows. The difference in spill-over ratio was reduced to <5% after 131I prompt emission correction. In the mouse model, the standard uptake value (SUV) did not differ significantly between FDG PET only (gold standard) and FDG PET after 131I prompt emission-correction, whereas it was overestimated by 38% before correction. Contrast was improved by 18% after 131I prompt emission correction. We first found that count contamination on 18F-FDG follow-up scans due to 131I spilled-over count after 131I rituximab tumor targeted therapy. Our developed 131I prompt emission-correction method increased accuracy during measurement of standard uptake values on 18F-FDG PET.

Derivation of occupational exposure limits for multi-walled carbon nanotubes and graphene using subchronic inhalation toxicity data and a multi-path particle dosimetry model.

In this study, we aimed to provide the recommended occupational exposure limits (OELs) for multi-walled carbon nanotubes (MWCNTs) and graphene nanomaterials based on data from a subchronic inhalation toxicity study using a lung dosimetry model. We used a no observed adverse effect level (NOAEL) of 0.98 mg m-3 and 3.02 mg m-3 in rats for MWCNTs and graphene, respectively. The NOAELs were obtained from a 13-week inhalation study in rats. The deposition fractions of MWCNTs and graphene in the respiratory tract of rats and humans were calculated by using the multi-path particle dosimetry model (MPPD model, v3.04). The deposition fraction in the alveolar region was 0.0527 and 0.0984 for MWCNTs and 0.0569 and 0.1043 for graphene in rats and human lungs, respectively. Then, the human equivalent exposure concentrations (HECs) of MWCNTs and graphene were calculated according to the method by the National Institute for Occupational Safety and Health (NIOSH). The HEC was estimated to be 0.17 mg m-3 for MWCNTs and to be 0.54 mg m-3 for graphene, which was relevant to the rat NOAEL of 0.98 mg m-3 and 3.02 mg m-3 for MWCNTs and graphene, respectively. Finally, we estimated the recommended OELs by applying uncertainty factors (UFs) to the HEC as follows: an UF of 3 for species differences (rats to humans), 2 for an experimental duration (subchronic to chronic), and 5 for inter-individual variations among workers. Thus, the OEL was estimated to be 6 µg m-3 for MWCNTs and 18 µg m-3 for graphene. These values could be useful in preventing the adverse health effects of nanoparticles in workers.

Lead, Mercury, and Cadmium Exposure in the Korean General Population.

BACKGROUND: Lead (Pb), mercury (Hg), and cadmium (Cd) are well-known environmental pollutants. They are unnecessary in the biological processes of humans. This study was performed to estimate the representative background exposure levels to the metals by measuring concentrations in whole blood of the Korean general population. METHODS: This population-based cross-sectional study included 4,000 subjects (1,886 males and 2,114 females) 0-83 years of age in 2010 and 2011. Adult subjects (≥ 19 years of age) were collected by sex- and age-stratified probability method, and preschool- and school-aged subjects were recruited by a cluster sampling method. Written consent was provided prior to blood sampling. Pb and Cd blood concentrations were determined by a flameless atomic absorption spectrophotometry, and blood Hg was analyzed by a direct Hg analyzer. RESULTS: The geometric mean, median and 95th percentile of blood Pb was 1.82 µg/dL, 1.83 µg/dL, and 3.78 µg/dL, respectively. The respective values were 2.92 µg/L, 2.87 µg/L, 9.12 µg/L for Hg, and 0.56 µg/L, 0.59 µg/L, 2.20 µg/L for Cd. Blood Pb and Hg were higher in males than in females, but no sex difference was observed, respectively, in subjects 0-4 years of age for Pb and in subjects less than 20 years for Hg. However, blood Cd was higher in females than in males and no sex difference was observed in subjects < 30 years of age. CONCLUSION: This study provides representative data of human exposure to Pb, Hg, and Cd covering whole age groups of the general population in Korea.

Fine needle aspiration of spindle cell ductal carcinoma in situ of the breast: A case report and the use of ancillary tests for the differential diagnosis of metaplastic carcinoma.

Spindle cell ductal carcinoma in situ (DCIS) is a recently recognized subtype of DCIS, which is associated with a very rare and unique morphology. Although the histologic features have been relatively well described in a few reports, the cytologic features have not. Even though the distinction of this lesion from usual DCIS is not crucial clinically, it should be noted that this lesion might simulate the features of metaplastic carcinoma on fine needle aspiration cytology. Here, we report a case of spindle cell DCIS in a 45-year-old female, with the detailed cytologic features, both on conventional and liquid-based preparations, along with some useful immunohistochemical staining markers for the differential diagnosis.

Low-Level Environmental Cadmium Exposure Induces Kidney Tubule Damage in the General Population of Korean Adults.

Cadmium (Cd) is the most potent nephrotoxic heavy metal and may affect bone; it also has a long biological half-life in the human body. This study was designed to assess the effect of environmental low-level Cd exposure on kidney function and bone in the general population. The subjects of this cross-sectional study were 1907 healthy Korean adults who had not been exposed to Cd occupationally. We analyzed the concentrations of Cd in the urine, markers of renal tubule damage, such as ß2-microglobulin (ß2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) activity in the urine, calculated the estimated glomerular filtration rate (eGFR) using serum creatinine, and measured bone mineral density (BMD). Also, we analyzed malondialdehyde (MDA) levels in the urine. The geometric mean concentration of Cd in urine was higher in women (1.36 µg/g creatinine) than in men (0.82 µg/g creatinine). Urinary Cd was significantly positively correlated with urinary ß2-MG and NAG activity, whereas it was negatively correlated with eGFR and BMD. The risk of renal tubule damage was significantly associated with urine Cd level, and the association remained significant after controlling for various confounding variables. However, no association was observed between urinary Cd level and glomerular dysfunction or bone damage. The concentration of MDA was increased with urinary Cd level in a dose-dependent manner. These findings suggest that low-level environmental Cd exposure may cause microscopic damage to renal tubules through oxidative stress but might not impair kidney glomeruli or bones.

Clinical efficacy of the classic laryngeal mask airway in elderly patients: a comparison with young adult patients.

BACKGROUND: The elderly have been reported to show anatomical and physiologic changes in the upper airway, which might affect the supraglottic airway (SGA) performance in geriatric populations. This study aimed to evaluate the clinical efficacy of the classic laryngeal mask airway (LMA-C) in the elderly compared with young adult patients. METHODS: Fifty patients aged 65-85 years (elderly group) and 50 patients aged 20-40 years (young group) who were scheduled for surgery using the LMA-C for general anesthesia were enrolled in this prospective, non-randomized, comparative study. Manipulations required during insertion, success rate, insertion time, oropharyngeal leak pressure, gastric insufflation, and intraoperative inadequate ventilation with the LMA-C were assessed. Fiberoptic evaluation was used to determine the position of the LMA-C. RESULTS: In the elderly group, the insertion success rate on the first attempt was significantly lower than that in the young group (84 vs. 96%, P = 0.02). The insertion time in the elderly group was significantly longer than that in the young group (28.5 ± 19.6 vs. 22.2 ± 6.4 seconds, P = 0.001). However, there was no difference in oropharyngeal leak pressure or fiberoptic grade between the two groups after proper placement of the LMA-C. During the surgery, inadequate ventilation events occurred more frequently in the elderly group than in the young group (31.3 vs. 4.0%, P < 0.001). CONCLUSIONS: The clinical efficacy of the LMA-C in elderly patients was inferior to that in young adult patients. Therefore, further studies are required to determine the type of SGA that can provide excellent clinical efficacy in the geriatric population.

Cytologic, clinicopathologic, and molecular features of papillary thyroid carcinoma with prominent hobnail features: 10 case reports and systematic literature review.

The hobnail variant of papillary thyroid carcinoma (PTC) is a rare, aggressive variant in which > 30% of the tumor cells have hobnail features. The clinical behavior and pathologic characteristics of these tumors are still unclear due to the rarity of the entity. The present study aimed to investigate cytologic, clinical, pathological, and molecular features of the hobnail variant from our data and from the literature. We retrospectively retrieved 10 cases of hobnail variant from 2,904 consecutive PTC patients. Cytologic and histopathologic slides from those 10 patients were reviewed. We performed molecular analysis for BRAF, ALK, and TERT promoter mutations on paraffin blocks from surgical specimens, and further analyzed the clinicopathologic characteristics of all case reports published in the literature until now. Cytologically, all tumors were characterized by single cells with eccentric nuclei and tapering cytoplasm (comet-like cells), and syncytial or micropapillary clusters with apically placed nuclei resulting in a hobnail appearance in both conventional smears and liquid-based cytology. The BRAF V600E mutation was found in 8 cases (80%) whereas no cases had ALK fusion or TERT promoter mutations. In the literature review of 55 patients including our cases, most patients presented with advanced stage cancer, and disease-specific survival rates were 83%, 71%, and 54% at 5, 10, and 20 years after the initial surgery, respectively. Characteristic cytologic features can allow a preoperative diagnosis of the hobnail variant of PTC based on cytology specimens. Further studies should be performed to identify the molecular genetics of the variant.

Cetaceans evolution: insights from the genome sequences of common minke whales.

BACKGROUND: Whales have captivated the human imagination for millennia. These incredible cetaceans are the only mammals that have adapted to life in the open oceans and have been a source of human food, fuel and tools around the globe. The transition from land to water has led to various aquatic specializations related to hairless skin and ability to regulate their body temperature in cold water. RESULTS: We present four common minke whale (Balaenoptera acutorostrata) genomes with depth of ×13 ~ ×17 coverage and perform resequencing technology without a reference sequence. Our results indicated the time to the most recent common ancestors of common minke whales to be about 2.3574 (95% HPD, 1.1521 - 3.9212) million years ago. Further, we found that genes associated with epilation and tooth-development showed signatures of positive selection, supporting the morphological uniqueness of whales. CONCLUSIONS: This whole-genome sequencing offers a chance to better understand the evolutionary journey of one of the largest mammals on earth.

Spatial resolution and image qualities of Zr-89 on Siemens Biograph TruePoint PET/CT.

PURPOSE: Zirconium-89 (t(1/2)=78.41 hours) is an ideal metallic radioisotope for immuno-positron emission tomography (PET), given that its physical half-life closely matches the biological half-life of monoclonal antibodies. In this study, the authors measured the spatial resolution and image quality of Zr-89 PET and compared the results against those obtained using F-18 PET, which is widely regarded as the gold standard for comparison of imaging characteristics. MATERIALS AND METHODS: The spatial resolution and image qualities of Zr-89 were measured on the Siemens Biograph Truepoint TrueV PET/CT scanner, partly according to NEMA NU2-2007 standards. For spatial resolution measurement, the Zr-89 point source was located at the center of the axial field of view (FOV) and offset 1/4 axial FOV from the center. For image quality measurements, an NEMA IEC Phantom was used. The NEMA IEC Phantom consists of six hot spheres that were filled with Zr-89 solution. Spatial resolution and image quality (%contrast, %background variability [BV], and source to background ratio [SBR]) were assessed to compare the imaging characteristics of F-18 with those of Siemens Biograph Truepoint TrueV. RESULTS: The transverse and axial spatial resolutions at 1 cm were 4.5 and 4.7 mm for Zr-89, respectively. The %contrast of Zr-89 was 25.5% for the smallest 10 mm sized sphere and 89.8% for the largest 37 mm sized sphere, and for F-18, it was 32.5% for the smallest 10 mm sized sphere and 103.9% for the largest 37 mm sized sphere using the ordered subset expectation maximization (OSEM) reconstruction method. The %BV of F-18 PET was 6.4% for the smallest 10 mm sized sphere and 3.5% for the largest 37 mm sized sphere using the OSEM reconstruction. The SBR of Zr-89 was 1.8 for the smallest 10 mm sized sphere and 3.7 for the largest 37 mm sized sphere, and for F-18, it was 2.0 for the smallest 10 mm sized sphere and 4.1 for the largest 37 mm sized sphere using the OSEM reconstruction method. CONCLUSIONS: This study assessed Zr-89 imaging characteristics using a Siemens Biograph Truepoint TrueV PET/CT scanner and compared the results with those obtained for F-18 PET. Although spatial resolution and image quality of Zr-89 PET were lower compared with F-18 PET, due to longer positron range and low positron branching ratio, Zr-89 is advantageous for immuno-PET due to well-matched half-life with monoclonal antibodies.