Metachronously Occurring Carcinomas of Different Histological Types in Bilateral Parotid Glands.

The occurrence of multiple malignant tumors with varying histological characteristics in bilateral parotid glands has never been documented previously in the literature. Here, the authors present a noteworthy case of a patient who exhibited the sequential development of primary carcinomas, each displaying distinct histologic types within the bilateral parotid glands. This case concerns a 57-year-old male patient who initially underwent surgery, followed by adjuvant radiotherapy, for squamous cell carcinoma diagnosed in the right parotid gland. Approximately 3 years after this treatment, a novel salivary duct carcinoma emerged within the left parotid gland, prompting a second round of surgical intervention, again followed by adjuvant radiotherapy. Subsequently, a recurrent tumor was identified within the left Stensen duct, necessitating additional surgical intervention. While monitoring for recurrence or metastases remains an important aspect of post-treatment care for salivary gland cancer, it is also imperative to consider the potential for developing a second primary salivary gland cancer.

Factors associated with discrepancy between fresh frozen and permanent biopsy from medical thoracoscopy: single center analysis of 172 medical flexible thoracoscopy cases.

BACKGROUND: Frozen sections prepared during medical thoracoscopy (MT) have precise diagnostic ability in pleural pathology and may assist in decision-making before pleurodesis. The present study evaluated the diagnostic sensitivity of frozen sections from flex-rigid MT, and further evaluated clinical parameters for their association with a discrepancy between frozen sections and permanent paraffin sections. METHODS: This retrospective study evaluated 172 patients who underwent flex-rigid MT between February 2017 and November 2019 at Incheon Saint Mary's Hospital. RESULTS: Of the 172 patients, 85 were pathologically diagnosed with malignancy based on permanent paraffin sections. An accurate diagnosis by fresh frozen section was feasible in 88.2% of the cases compared to the permanent paraffin sections. Among the 85 patients, 75 had malignancies in frozen sections, while 10 patients showed otherwise. In the 85 malignant cases, age, sex, the volume of effusion, thoracoscopic findings, as well as the final pathological diagnosis (lung vs. non-lung origin) were included in univariate analysis for an association with non-malignant frozen section results. High adhesion grade and malignancy other than lung cancer were significant factors associated with frozen section negative cases in a multivariable analysis. CONCLUSIONS: Taking fresh frozen sections during MT using a flex-rigid bronchoscope is a useful diagnostic modality with reliable sensitivity for malignancy. However, if the pre-procedural diagnosis is likely to be a malignancy other than lung cancer, and if severe adhesions are present in the pleural cavity, the final pathological confirmation should be determined based on permanent paraffin sections, not only on fresh frozen sections.

Prognostic Significance of Stromal and Intraepithelial Tumor-Infiltrating Lymphocytes in Small Intestinal Adenocarcinoma.

OBJECTIVES: Assessment of tumor-infiltrating lymphocytes (TILs) may predict the prognosis and therapeutic benefit of immunotherapy in small intestinal adenocarcinoma (SIAC) patients. METHODS: TILs were evaluated in 231 surgically resected SIACs and compared with microsatellite instability (MSI) and clinicopathologic variables. The average number of intraepithelial TILs (iTILs) and the average density of stromal TILs (sTILs) were calculated separately. RESULTS: High iTIL count (≥2 per high-power field) was associated with MSI-high, whereas high sTIL density (≥20% on ×200 magnification) was not. High iTIL count and high sTIL density were related to distal tumor location, medullary carcinoma, high Crohn-like lymphoid reaction counts, and fewer pancreatic invasions. SIAC patients with high iTIL count or high sTIL density had better survival than those with low values. On multivariate analysis, MSI, high sTIL density, proximal locations, lower N category, and absence of lymphovascular invasions and retroperitoneal seeding were the best independent prognostic predictors. CONCLUSIONS: High sTIL density can be used as a prognostic indicator and high iTIL count may provide a basis for the clinical use of targeted immunotherapy in SIAC patients.

Delayed Treatment of Capsaicin Produces Partial Motor Recovery by Enhancing Dopamine Function in MPP+-lesioned Rats via Ciliary Neurotrophic Factor.

Transient receptor potential vanilloid subtype 1 (TRPV1) on astrocytes prevents ongoing degeneration of nigrostriatal dopamine (DA) neurons in MPP+-lesioned rats via ciliary neurotrophic factor (CNTF). The present study determined whether such a beneficial effect of astrocytic TRPV1 could be achieved after completion of injury of DA neurons, rather than ongoing injury, which seems more relevant to therapeutics. To test this, the MPP+-lesioned rat model utilized here exhibited approximately 70~80% degeneration of nigrostriatal DA neurons that was completed at 2 weeks post medial forebrain bundle injection of MPP+. TRPV1 agonist, capsaicin (CAP), was intraperitoneally administered. CNTF receptor alpha neutralizing antibody (CNTFRαNAb) was nigral injected to evaluate the role of CNTF endogenously produced by astrocyte through TRPV1 activation on DA neurons. Delayed treatment of CAP produced a significant reduction in amphetamine-induced rotational asymmetry. Accompanying this behavioral recovery, CAP treatment increased CNTF levels and tyrosine hydroxylase (TH) activity in the substantia nigra pars compacta (SNpc), and levels of DA and its metabolites in the striatum compared to controls. Interestingly, behavioral recovery and increases in biochemical indices were not reflected in trophic changes of the DA system. Instead, behavioral recovery was temporal and dependent on the continuous presence of CAP treatment. The results suggest that delayed treatment of CAP increases nigral TH enzyme activity and striatal levels of DA and its metabolites by CNTF endogenously derived from CAP-activated astrocytes through TRPV1, leading to functional recovery. Consequently, these findings may be useful in the treatment of DA imbalances associated with Parkinson's disease.

Prominent Nucleoli and Non-glandular Feature Are Independent Predictors of PD-L1 Expression in Lung Adenocarcinoma.

BACKGROUND/AIM: In patients with non-small cell lung cancer, relationships between PD-L1 (programmed death-ligand 1) expression and clinicopathological characteristics have been examined. However, the association between cytological features and PD-L1 expression remains unknown. Thus, the aim of this study was to investigate whether nuclear features might be correlated with PD-L1 expression in patients with advanced and inoperable lung adenocarcinoma using small biopsy specimens. MATERIALS AND METHODS: Archived slides from 90 patients with lung adenocarcinoma who underwent small biopsy between October 2014 and May 2017 at the Incheon St. Mary's Hospital, were reviewed. PD-L1 expression was detected by immunohistochemistry using PD-L1 22C3 IHC assay. Associations of PD-L1 expression with pathological and molecular features (EGFR mutation, ALK and ROS-1 rearrangement) were statistically analyzed. RESULTS: PD-L1 expression in tumor cells was positive in 33 of 90 cases (36.7%). Higher PD-L1 expression (≥50%) was more frequent in cases with marked nuclear pleomorphism (p<0.001), coarse chromatin pattern (p=0.006), predominant nucleoli (≥3 µm) (p<0.001), large nuclear diameter (>5× small lymphocyte) (p=0.006), non-glandular feature (p<0.001), and atypical mitosis (p=0.034). There were no significant correlations between PD-L1 positivity and molecular features. In multivariable logistic regression analysis, PD-L1 positivity was independently associated with prominent nucleoli (p=0.005) and non-glandular feature (p=0.007). CONCLUSION: Prominent nucleoli and non-glandular feature are independent predictors of PD-L1 expression in lung adenocarcinoma.

Sustained multiple organ ischaemia after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma.

Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads) may enhance drug delivery to tumours and reduce systemic toxicity. TACE with DC beads leads to significantly fewer serious side-effects compared with conventional TACE. A 66-year-old man with hepatocellular carcinoma (HCC) complained of continuous abdominal pain 1 month after TACE with DC beads. At the time of TACE, angiography revealed severe stenosis of both hepatic arteries. The diagnostic work up on admission suggested severe bile duct injury with regional bile duct dilatation, segmental liver and spleen infarction, necrotizing pancreatitis, as well as gastric and duodenal ulcers. The pathology specimens of the duodenum contained DC beads that had passed through small vessels in the connective tissue. The patient's condition appeared to improve after 2 weeks of antibiotic treatment and supportive care, but new multifocal liver and spleen infarction subsequently developed. After 2 months, he was well enough to be discharged. His HCC partially responded to the TACE with DC beads but eventually progressed and he died after 11 months. The present case report highlights unexpected ongoing multiple organ ischaemia in a 66-year-old man treated for HCC using TACE with DC beads. The use of TACE with DC beads should be carefully considered in patients with vascular strictures or aberrant blood supply.

Characteristics and prognosis of glomangiopericytomas: A systematic review.

BACKGROUND: Glomangiopericytoma belongs to the category of borderline/low-malignant-potential tumors of the sinonasal tract, but no studies about prognosis have been reported. METHODS: To define the characteristics of glomangiopericytoma and to identify its prognostic factors, a systematic review was performed. A total of 337 cases of glomangiopericytomas were analyzed. RESULTS: Patients with glomangiopericytoma demonstrating resection margin involvement and receiving radiotherapy/chemotherapy had a significantly worse disease-free survival time (P = .014 and .006, respectively). Patients with glomangiopericytoma had a tendency toward longer overall survival when they were diagnosed at a younger age (≤60 years; P = .001), did not demonstrate marginal involvement (P = .032), recurrence/metastasis (P = .002), or radiotherapy/chemotherapy (P = .010), and had a right-sided tumor (P < .001), actin-immunopositivity (P < .001), and CD34-/BCL2-immunonegativities (P = .002 and .019, respectively). By multivariate analysis, actin (P < .001) and CD34 (P = .002) immunostaining were significantly related to the overall survival of patients with glomangiopericytoma. CONCLUSION: Actin and CD34 immunostaining could be used as independent prognostic indicators of glomangiopericytomas.

Low grade myxofibrosarcoma in the right ventricle presenting as pulmonary thromboembolism.

We report an unusual malignant cardiac neoplasm that initially presented as pulmonary thromboembolism in a 78-year-old male. Despite anticoagulation, the pulmonary artery lesion progressed and a mass-like lesion developed in the right ventricular outflow tract. Venoarterial extracorporeal membrane oxygenation was applied before surgery due to the presence of severe right-side heart failure with pulmonary hypertension. A round mass was found in the right ventricle and separate lobulated masses were found in both pulmonary arteries, and these were consistent with low-grade myxofibrosarcoma.

Clinicopathologic Characteristics and Mutational Status of Succinate Dehydrogenase Genes in Paraganglioma of the Urinary Bladder: A Multi-Institutional Korean Study.

CONTEXT: - Because of the limited number of available primary bladder paraganglioma (PBPG) cases, the rates of succinate dehydrogenase (SDH) mutations and the clinicopathologic characteristics of SDH-deficient tumors have not been fully studied. OBJECTIVE: - To define the clinicopathologic and molecular characteristics of PBPGs. DESIGN: - A total of 52 PBPGs were collected retrospectively. SDHA and SDHB immunohistochemical stains were performed. In cases of SDHB expression loss, mutation analyses of SDHB, SDHC, and SDHD were performed. RESULTS: - The clinicopathologic features were analyzed for 52 cases (M:F = 27:25), with a mean age of 56 years (range, 22-79 years). Tumor sizes were 0.5 to 8 cm (mean, 2.4 cm). Tumor necrosis was present in 5 of 52 cases (10%), involvement of muscularis propria in 41 (79%), and lymphovascular tumor invasion in 6 (12%). During a mean follow-up period of 41 months (range, 1-161 months), 3 of 52 patients (6%) developed metastases, but no one died from the disease. Immunohistochemistry for SDHA and SDHB showed that all cases were SDHA intact. Among them, 43 cases had intact SDHB, whereas 9 cases were SDHB deficient. Compared with the SDHB-intact cases, the SDHB-deficient cases were characterized by large tumor sizes (4.5 versus 1.9 cm; P < .001), a higher number of mitoses per 10 high-powered fields (2.6 versus 0.1; P = .002), and frequent lymphovascular tumor invasion (33% versus 7%; P = .02) and metastases (22% versus 2%; P = .02). Mutational analyses for SDHB, SDHC, and SDHD were performed in 9 SDHB-deficient cases. Among them, 6 cases were successfully sequenced and revealed SDHB mutations only. CONCLUSIONS: - Large tumor size, a higher number of mitoses, and the presence of lymphovascular tumor invasion and SDHB mutations suggest malignant paraganglioma.

Inflammatory signals induce the expression of tonicity-responsive enhancer binding protein (TonEBP) in microglia.

Tonicity-responsive enhancer (TonE) binding protein (TonEBP) is known as an osmosensitive transcription factor that regulates cellular homeostasis during states of hypo- and hypertonic stress. In addition to its role in osmoadaptation, growing lines of evidence suggest that TonEBP might have tonicity-independent functions. In particular, a number of studies suggest that inflammatory stimuli induce the expression and activation of TonEBP in peripheral immune cells. However, whether TonEBP is expressed in microglia, resident immune cells of the central nervous system, is unknown. Here we show that inflammatory signals induce the expression of TonEBP in microglia both in vitro and in vitro. In cultured primary microglia, treatment with lipopolysaccharide (LPS), interferon-γ, and interleukin 4 increased the expression of TonEBP. Moreover, we found that stereotaxic injection of LPS into the substantia nigra region of rat brain increased TonEBP expression in OX-42-positive cells. Furthermore, expression of TonEBP was induced in OX-42-positive cells in a rat model of transient middle cerebral artery occlusion. Together these results show that the expression of TonEBP is regulated by inflammatory signals in mammalian brain, suggesting that TonEBP might play a part during neuroinflammation.

Efficiency of an automated reception and turnaround time management system for the phlebotomy room.

BACKGROUND: Recent advances in laboratory information systems have largely been focused on automation. However, the phlebotomy services have not been completely automated. To address this issue, we introduced an automated reception and turnaround time (TAT) management system, for the first time in Korea, whereby the patient's information is transmitted directly to the actual phlebotomy site and the TAT for each phlebotomy step can be monitored at a glance. METHODS: The GNT5 system (Energium Co., Ltd., Korea) was installed in June 2013. The automated reception and TAT management system has been in operation since February 2014. Integration of the automated reception machine with the GNT5 allowed for direct transmission of laboratory order information to the GNT5 without involving any manual reception step. We used the mean TAT from reception to actual phlebotomy as the parameter for evaluating the efficiency of our system. RESULTS: Mean TAT decreased from 5:45 min to 2:42 min after operationalization of the system. The mean number of patients in queue decreased from 2.9 to 1.0. Further, the number of cases taking more than five minutes from reception to phlebotomy, defined as the defect rate, decreased from 20.1% to 9.7%. CONCLUSIONS: The use of automated reception and TAT management system was associated with a decrease of overall TAT and an improved workflow at the phlebotomy room.

Comparison of the Cobas 4800 HPV and HPV 9G DNA Chip Tests for Detection of High-Risk Human Papillomavirus in Cervical Specimens of Women with Consecutive Positive HPV Tests But Negative Pap Smears.

Detecting high-risk (HR) HPV is important for clinical management of women with persistent HPV-positive and Pap-negative results. The Cobas 4800 HPV test is the first FDA-approved HPV DNA test that can be used alone as a first-line screening tool. The HPV 9G DNA chip test is a PCR-based DNA microarray assay. We evaluated the patients of consecutive HPV-positivity on HPV 9G DNA chip test without cytologic abnormalities. We then compared the performances of HPV 9G DNA chip and the Cobas 4800 HPV tests for detecting HR HPV with each other and confirmed HPV genotyping using direct sequencing. All 214 liquid-based cytology specimens were collected from 100 women with consecutive HPV-positive and Pap-negative results on the HPV 9G DNA chip test between May 2012 and Dec 2013, but only 180 specimens were available for comparing HPV test results. The HPV 9G DNA chip and the Cobas 4800 HPV tests agreed with each other in 81.7% of the samples, and the concordance rate was greater than 97.2% for detecting HPV-16 or -18. For HR genotypes other than HPV types 16 and 18, the two tests agreed for 81.1% of the samples. The sensitivity of both assays for detecting HR HPV was 100%, regardless of HR genotypes. The HPV 9G DNA chip test may be as effective as the Cobas 4800 HPV test in detecting HR HPV, and has a similar ability to identify HPV-16 and -18.

Cancer-Testis Antigen Expression in Serous Endometrial Cancer with Loss of X Chromosome Inactivation.

BACKGROUND: Cancer-testis antigens (CTAs) are potential targets for cancer immunotherapy. Many CTAs are located on the X chromosome and are epigenetically regulated. Loss of X chromosome inactivation (XCI) is observed in breast and ovarian cancers and is thought to be related to the overexpression of CTAs. We investigated the relation between expression of CTAs and loss of XCI in endometrial cancer. MATERIALS AND METHODS: We used data generated by The Cancer Genome Atlas Genome Data Analysis Centers and data for Xist knockout mice available at the Gene Expression Omnibus. RESULTS: The status of XCI was estimated by methylation status, and deletion or gain of the X chromosome. The endometrial cancers were classified into the following three groups: preserved inactivated X chromosome (Xi) (n = 281), partial reactivation of Xi (n = 52), and two copies of active X group (n = 38). Loss of XCI was more common in serous adenocarcinoma. Expression of CTAs increased in endometrial cancer with loss of XCI, which was accompanied by global hypomethylation. Expression of CTAs did not increase in Xist knockout mice. CONCLUSIONS: Loss of XCI is common in serous adenocarcinoma. Global hypomethylation, and not loss of XCI, is the main mechanism of overexpression of CTAs.

Gastric metastasis from primary lung adenocarcinoma mimicking primary gastric cancer.

Gastric metastases from lung adenocarcinoma are rare. Because gastric metastasis grossly resembles advanced gastric cancer, it is difficult to diagnose gastric metastasis especially when the histology of the primary lung cancer is adenocarcinoma. We describe a case of gastric metastasis from primary lung adenocarcinoma mimicking Borrmann type IV primary gastric cancer. A 68-year-old man with known lung adenocarcinoma with multiple bone metastases had been experiencing progressive epigastric pain and dyspepsia over one year. Esophagogastroduodenoscopy revealed linitis plastica-like lesions in the fundus of the stomach. Pathologic examination revealed a moderately differentiated adenocarcinoma with submucosal infiltration. Positive immunohistochemical staining for thyroid transcription factor-1 (TTF-1) and napsin A (Nap-A) confirmed that the metastasis was pulmonary in origin. The patient had been treated with palliative chemotherapy for the lung cancer and had lived for over fifteen months after the diagnosis of gastric metastasis. Clinicians should be aware of the possibility of gastric metastasis in patients with primary lung adenocarcinoma, and additional immunohistochemical staining for Nap-A as well as TTF-1 may help in differentiating its origin.

Cold snare polypectomy versus cold forceps polypectomy for diminutive and small colorectal polyps: a randomized controlled trial.

BACKGROUND: The optimal technique for removal of diminutive or small colorectal polyps is debatable. OBJECTIVE: To compare the complete resection rates of cold snare polypectomy (CSP) and cold forceps polypectomy (CFP) for the removal of adenomatous polyps ≤7 mm. DESIGN: Prospective randomized controlled study. SETTING: A university hospital. PATIENTS: A total of 139 patients who were found to have ≥1 colorectal adenomatous polyps ≤7 mm. INTERVENTIONS: Polyps were randomized to be treated with either CSP or CFP. After the initial polypectomy, additional EMR was performed at the polypectomy site to assess the presence of residual polyp tissue. MAIN OUTCOME MEASUREMENTS: Absence of residual polyp tissue in the EMR specimen of the polypectomy site was defined as complete resection. RESULTS: Among a total of 145 polyps, 128 (88.3%) were adenomatous polyps. The overall complete resection rate for adenomatous polyps was significantly higher in the CSP group compared with the CFP group (57/59, 96.6% vs 57/69, 82.6%; P = .011). Although the complete resection rates for adenomatous polyps ≤4 mm were not different (27/27, 100% vs 31/32, 96.9%; P = 1.000), the complete resection rates for adenomatous polyps sized 5 to 7 mm was significantly higher in the CSP group compared with the CFP group (30/32, 93.8% vs 26/37, 70.3%; P = .013). LIMITATIONS: Single-center study. CONCLUSION: CSP is recommended for the complete resection of colorectal adenomatous polyps ≤7 mm. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01665898.).

Diagnostic usefulness of real-time elastography for liver fibrosis in chronic viral hepatitis B and C.

The aim of this study was to investigate the diagnostic usefulness of real-time elastography (RTE) for liver fibrosis in chronic viral hepatitis B (CHB) and C (CHC). Fifty-one and thirty-two of the patients were diagnosed with CHB and CHC, respectively. Enrolled patients underwent liver biopsy and RTE. The FIB-4 index and aspartate transaminase-to-platelet ratio index (APRI) were also measured. The liver fibrosis index (LFI) by RTE increased significantly with the Knodell fibrosis stage: 3.14 ± 0.62 for F0, 3.28 ± 0.42 for F1, 3.43 ± 0.53 for F3, and 4.09 ± 1.03 for F4 (P = 0.000). LFI as well as APRI, FIB-4, platelet, albumin, and prothrombin time showed the difference in patients with advanced fibrosis (≥F3) and those with mild fibrosis (≤F1). In addition, RTE had better discrimination power between ≥F3 and F4 than between FIB-4 and APRI. In CHC patients, the area under receiver operating characteristic curves of RTE for advanced fibrosis was higher than that in CHB patients (0.795 versus 0.641). RTE is useful for the assessment of advanced fibrosis in patients with CHB and CHC and has better discrimination power than other serologic markers.

Comparison of total and IgG ABO antibody titers in healthy individuals by using tube and column agglutination techniques.

BACKGROUND: Most immune reactions related to transfusion and transplantation are caused by IgM ABO antibodies. However, IgG also plays an important role in these reactions. Therefore, a method to measure antibodies, including IgG, is necessary. We investigated ABO antibody titers of healthy individuals using a column agglutination technique (CAT) with or without dithiothreitol (DTT) and compared them with titers obtained using a conventional tube method. METHODS: Among healthy adults who underwent a medical examination, 180 individuals (60 with blood group A, 60 with group B, and 60 with group O) were selected. Antibody titrations were performed using the immediate spin (IS) tube, anti-human globulin (AHG) tube, and CAT with or without DTT methods. RESULTS: Higher median values of anti-B and anti-A titers in groups A and B individuals, respectively, were obtained using the IS method than using the AHG method. Higher values for group O individuals were obtained using the AHG method. Higher median titers of anti-B and anti-A in group O individuals were obtained using CAT without DTT than using the AHG method. Median titers of anti-B and anti-A in all blood groups were higher in CAT without DTT than in CAT with DTT, especially for group O individuals. CONCLUSIONS: We recommend CAT with and without DTT for titration of anti-A and anti-B, especially in group O individuals, to provide more sensitive results that include IgG data. Adjustment of insurance coverage of fees associated with antibody titration might be necessary, considering the actual cost of reagents and personnel.

Overflow proteinuria as a manifestation of unrecognized polymyositis.

Polymyositis is a rare and gradually progressive autoimmune disease of skeletal muscle. Two main types of renal involvement have been described: acute tubular necrosis related to rhabdomyolysis and glomerulonephritis. However, cases of overflow proteinuria related to polymyositis have rarely been reported. Herein, we report a case of a 41-year-old male who presented with edema of both lower extremities. Laboratory studies revealed elevated creatine phosphokinase level, hypoalbuminemia, and a moderate amount of proteinuria, although albuminuria was not dominant. Urine electrophoresis showed an abnormally restricted zone in the ß-fraction, which suggested overflow proteinuria of non-glomerular origin. Despite intravenous hydration, his serum creatine phosphokinase level did not decrease and his symptoms did not improve. Electromyography showed myopathy, and muscle biopsy revealed findings consistent with polymyositis. After corticosteroid therapy, his creatine phosphokinase level and proteinuria decreased and his clinical symptoms improved. This case demonstrates an atypical presentation of polymyositis manifested by overflow proteinuria.