bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Exo-EphA2 as a Potential Diagnostic Biomarker for Pancreatic Cancer
Authors: Wei Qian , Zhang Jingya , Li Ze , Wei Lijuan , Ren Li
Published: September 2020

Objectives

Pancreatic cancer (PC) is a highly malignant tumor with poor detection sensitivity and specificity in biomarkers and diagnosis. Previous research indicated that serum Ephrin type-A receptor 2 in exosomes (Exo-EphA2) was highly expressed and might have facilitated cell migration in PC cells. However, the dynamics of clinical performance of serum Exo-EphA2 in PC patients are unknown. Thus, this study evaluated serum Exo-EphA2 as a potential diagnostic biomarker in PC.

Methods

The expressions of serum Exo-EphA2 were assessed by enzyme-linked immunosorbent assay for N = 353 serum samples, including from 204 PC patients, 75 patients with benign pancreatic disease, and 74 healthy control patients. Carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 242 (CA 242) were measured by automated immunoassay.

Results

Serum Exo-EphA2 levels were significantly higher in PC patients than in benign pancreatic disease and healthy control patients. Receiver operating characteristic curve analysis suggested that using combined diagnoses of Exo-EphA2 with CA 19-9 and CA 242 was more effective to discriminate early stage (stage I and II) in PC than in healthy controls and benign disease patients.

Conclusions

Novel findings suggest that serum Exo-EphA2 is a potential early diagnostic biomarker complementing CA 19-9 and CA 242 in PC.
Immunological Gene Signature Associated With the Tumor Microenvironment of Pancreatic Cancer After Neoadjuvant Chemotherapy
Authors: Hane Yuma , Tsuchikawa Takahiro , Nakamura Toru , Hatanaka Kanako C. , Saito Tatsuro , Tanaka Kimitaka , Nakanishi Yoshitsugu , Asano Toshimichi , Noji Takehiro , Okamura Keisuke , Shichinohe Toshiaki , Yokota Isao , Hatanaka Yutaka , Hirano Satoshi
Published: September 2020

Objectives

Neoadjuvant chemotherapy (NAC) has improved overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but its effects on immune gene signatures are unknown. Here, we examined the immune transcriptome after NAC for PDAC.

Methods

Resected tumor specimens were obtained from 140 patients with PDAC who received surgery first (n = 93) or NAC (n = 47). Six patients were randomly selected from each group, and RNA was extracted from tumor tissues. We compared 770 immune-related genes among the 2 groups using nCounterPanCancer Immune Profiling (NanoString Technologies, Seattle, Wash). Gene clusters were classified into 14 immune function groups based on gene ontology argolism by nSolver 4.0 software (NanoString Technologies), and corresponding immune cell function scores were compared.

Results

Eleven genes (LY86, SH2D1A, CD247, TIGIT, CR2, CD83, LAMP3, CXCR4, DUSP4, SELL, and IL2RA) were significantly downregulated in the NAC group. Gene expression analysis showed that the functions of regulatory T cells, B cells, and natural killer CD56 dim cells were significantly decreased in the NAC group.

Conclusions

Neoadjuvant chemotherapy may suppress regulatory T cells and B-cell function in the PDAC microenvironment. The 11 identified genes could be useful for predicting the efficacy of NAC and could be therapeutic targets for PDAC.
A short-term oral corticosteroid for refractory lumbar spinal stenosis: a double-blinded randomized placebo-controlled clinical trial
Authors: Akbari Aghdam Hossein , Andalib Ali , Asadiyan Ardakani Hossein , Telloo Mahshid , Sheikhbahaei Erfan
Published: September 2020

Although epidural corticosteroids have been evaluated for the lumbar spinal stenosis (LSS) as an alternative treatment, oral corticosteroids have not been considered as a possible option for the patients with constant pain who have resistant against routine treatments. Therefore, this study aimed to investigate the efficacy of the short-term, low-dose oral prednisolone for refractory LSS. In this double-blinded randomized placebo-controlled clinical trial, 100 participants with the refractory LSS were selected from the out-patient clinics; however, 7 of them excluded before randomization. The patients were randomly allocated into two groups with a 1:1 ratio: the intervention group that received 10 mg prednisolone per day for 1 week and the control group that received the exact placebo. The patients’ severity of pain in terms of the numerical rating scale, ability to walk in meters, and Oswestry Disability Index (ODI) were assessed and then compared to the baseline after 2 months. The baseline variables were NS between these two groups. At the 2-month follow-up, the ability to walk in meters has increased and the severity of pain and ODI have decreased in both groups. Notably, except for the walking distance, none of the differences were statistically significant. Except for the significant change in walking distance between the groups, no other significant difference was observed in any variables when comparing the delta of each variable (after–before). One-week treatment with daily 10 mg oral prednisolone was not effective on the patients with refractory LSS in the short-term follow-up.
Effect of a training program of overground walking on BTS gait parameters in elderly women during single and dual cognitive tasks
Authors: Hagner-Derengowska Magdalena , Kałużny Krystian , Kałużna Anna , Zukow Walery , Leis Kamil , Domagalska-Szopa Małgorzata , Kochański Bartosz , Budzyński Jacek
Published: September 2020

We tested the hypothesis that a regular training program might reduce gait disturbances during dual cognitive-motor tasks in elderly women. This open-label experimental study comprised 53 postmenopausal women aged over 65, who were assigned to a 10-week training program (360 min/week). A BTS SMART system examination during free walking and during dual tasks [i.e., walking while performing either a simple (SCT) or a complex (CCT) cognitive task] was performed prior to the training program and again after it had finished. After the 10-week walking training program, a significant decrease was found in the duration of single support phase, double support phase, total support phase, and gait cycle, whereas values for such BTS parameters as swing speed, step length, and gait speed increased significantly. The greatest percentage deltas between the final and initial values of the respective BTS parameters concerned swing speed and gait speed irrespective of the kind of task undertaken while measurements were taken. A cognitive task, irrespective of the level of difficulty, performed during walking had the opposite effect on step width than expected. A 10-week training program significantly improved the cadency and manner of gait in elderly women, but did not change step width. Therefore, further study is needed to estimate the usefulness of cognitive-motor training programs for significant improvement in gait coordination during dual tasks in elderly women.
Interprofessional Simulation to Improve the Understanding of Obstetric Sepsis
Authors: Frost Kristen , North Faith , Smith Kari
Published: September 2020

Sepsis parameters are not well defined for the obstetric population, which can result in delayed recognition. The escape room-based simulation sought to improve obstetric providers’ and nurses’ understanding, identification, and timely treatment of maternal sepsis. Participants expressed interest and enthusiasm in using this learning style to improve care of the sepsis patient. This intervention proved beneficial to staff development educators as an innovative and effective way to improve interprofessional engagement and promote knowledge of maternal sepsis.
Critical Analysis of Laboratory Testing Methodologies When Interpreting Conflicting Results at Autopsy
Authors: Johnson Kimberly Margaret , Gunsolus Ian L. , Tlomak Wieslawa
Published: September 2020

Toxicological analysis is an important diagnostic component of a postmortem examination and may involve both antemortem and postmortem specimens. Here, we present a case in which an antemortem specimen, when reanalyzed in the forensic toxicology laboratory, resulted in values that contradicted the reported values from the medical record and required further investigation. This case involves a 51-year-old man decedent with a medical history of chronic alcohol abuse. His antemortem urine drug screen, performed upon admission to an emergency department, was negative. His serum blood alcohol level at presentation was reported as 0.960 g/dL and, repeated 4 hours later, was 0.500 g/dL with a comment indicating that there was significant lipemia interfering with the results. At autopsy, the antemortem blood sample collected from the hospital, postmortem blood, and vitreous humor samples were analyzed and all 3 samples were found to be negative for ethanol. The hospital laboratory used an enzymatic assay for ethanol detection, which is known to be impacted by lipemia, and the forensic laboratory used head-space gas chromatography, which is not impacted by lipemia. This highlights the need to critically analyze laboratory testing methodologies when interpreting conflicting results at autopsy.
Cervical Superficially Invasive Squamous Cell Carcinoma With Supraclavicular Lymph Node Metastasis: A Case Report
Authors: Kawashita Sayaka , Matsuda Katsuya , Matsuwaki Takahiro , Kurohama Hirokazu , Ito Masahiro , Kishikawa Masao , Miura Kiyonori , Nakashima Masahiro
Published: September 2020

Typically, local spread and lymph-vascular space invasion (LVSI) occur before lymph node (LN) and distant metastases during the progression of uterine cervical cancer. The prognostic value of LVSI in cervical superficially invasive squamous cell carcinoma (SISCC) is still debated. We encountered a rare case of cervical SISCC without LVSI presenting with multiple LN metastases, including pelvic, para-aortic, and left supraclavicular LNs. Immunohistochemical analysis of p16INK4a and in situ hybridization of human papillomavirus confirmed the relationship of the cervical SISCC and pelvic LN metastases. Aspiration cytology of the left supraclavicular LN showed squamous cell carcinoma and our final diagnosis was uterine cervical squamous cell carcinoma, stage IVB. The patient underwent adjuvant chemotherapy. Although relapse was observed at the vaginal stump and in pelvic and para-aortic LNs, chemotherapy and radiotherapy were effective. The patient is alive without disease 40 mo after initial treatment. This is the first case report of cervical SISCC without LVSI presenting with supraclavicular LN metastasis, which contributes to our understanding of the value of LVSI. Immunohistochemical analysis of p16INK4a and in situ hybridization of human papillomavirus were useful in confirming the relationship of cervical SISCC and its metastases. As cervical SISCC with LN metastasis is rare, multi-institutional joint research is needed to clarify its prognosis and appropriate treatment.
Trefoil Factor 2 (TFF2) as a Surrogate Marker for Endocervical Gastric-type Carcinoma
Authors: Takako Kiyokawa , Hoang Lien , Terinte Cristina , Pesci Anna , Aviel-Ronen Sarit , Alvarado-Cabrero Isabel , Oliva Esther , Park Kay J. , Soslow Robert A. , Stolnicu Simona
Published: September 2020

Gastric-type carcinoma (GAS) is the most common human papilloma virus–independent endocervical adenocarcinoma (ECA), characterized by an aggressive behavior. Trefoil factor 2 (TFF2) is a mucin-associated peptide expressed in normal gastric but not endocervical glands. This study was carried out to investigate whether TFF2 could be a surrogate marker to separate GAS from other types of ECA. ECAs from 9 international institutions were reviewed for consensus histotype. Of them, expression of TFF2 was immunohistochemically examined compared with that of HIK1083, using whole sections of 50 ECAs (10 GASs and 40 non-GASs) and 179 ECAs (24 GASs and 155 non-GASs) with tissue microarrays (TMAs). TMAs were assessed to simulate assessment of immunohistochemical stains in small biopsies. Both markers were similarly scored, and any cytoplasmic/membranous staining of >5% of tumor cells was considered positive. Of 50 ECAs with whole sections, TFF2 was significantly more frequently expressed in GASs (8/10) compared with non-GASs (5/40) (P<0.01). In 179 ECAs with TMAs, TFF2 was also significantly more frequently expressed in GASs (7/24) compared with non-GASs (4/155) (P<0.01). There was no significant difference in specificity among the 2 markers. Double positivity for TFF2 and HIK1083 in ECAs was highly specific in separating GASs from non-GAS (P<0.01). A significantly smaller percentage of GASs were TFF2 positive in TMAs than in whole sections (P<0.01). Our results suggest that TFF2 is a promising marker, along with HIK1083, to confirm a diagnosis of GAS. This marker may be negative in small biopsies, indicating the necessity of using other exclusionary markers in combination with rigorous morphologic review and extensive sampling in resection specimens.
Late Development of Metastatic Ovarian Mucinous Adenocarcinoma From Primary Gallblader Adenocarcinoma and High-grade Dysplasia
Authors: Taylor Jennifer , Shah Rajeev , McElvanna Kevin , Kelly Paul J. , McCluggage W. Glenn
Published: September 2020

The ovary is a common site of metastatic mucinous adenocarcinoma. In most, but not all, cases the presence of a primary neoplasm elsewhere is already known and the metastasis is picked up at diagnosis or is discovered a relatively short time following the diagnosis of the primary neoplasm. We report 2 cases of metastatic gallbladder adenocarcinoma involving the ovaries of women aged 65 and 59 after long time periods of 8 and 5 yr following diagnosis of high-grade dysplasia or early adenocarcinoma of the gallbladder, respectively. In both cases, a review of the original operative notes suggested the possibility of intraoperative gallbladder rupture or bile leakage suggesting that the metastatic disease may have developed secondary to “seeding.” In both cases, p53 immunohistochemistry revealed identical null mutation-type immunoreactivity within the gallbladder and ovarian neoplasms, assisting in confirming the ovarian disease as a metastasis from the gallbladder. The possibility of late ovarian metastasis of gallbladder dysplasia or adenocarcinoma secondary to rupture/bile leakage should be borne in mind.
Diffuse Intratumoral Stromal Inflammation in Ovarian Clear Cell Carcinoma is Associated With Loss of Mismatch Repair Protein and High PD-L1 Expression
Authors: Lin Shih-Yao , Hang Jen-Fan , Lin Yen-Yu , Lai Chiung-Ru , Ho Hsiang‑Ling , Chou Teh-Ying
Published: September 2020

Ovarian clear cell carcinoma (OCCC) is an aggressive chemotherapy-resistant cancer with limited treatment options, and some OCCCs have mismatch repair (MMR) deficiency (MMRD). Emerging evidence has revealed that various cancers with MMRD are susceptible to anti-programmed death-1/programmed death ligand-1 (anti-PD-1/PD-L1) immunotherapy, and certain histologic features are associated with MMRD. However, few studies have addressed this in OCCC. We reviewed 76 OCCCs for tumor-associated inflammation (intratumoral stromal inflammation and peritumoral lymphocytes) and performed immunohistochemistry for 4 MMR proteins and PD-L1. MMR-deficient OCCCs were analyzed for microsatellite instability (MSI), and those with MLH1 loss were tested for MLH1 promoter methylation. No patients fulfilled the Amsterdam II criteria for the diagnosis of Lynch syndrome. Four (5.3%) tumors showed diffuse intratumoral stromal inflammation obliterating the tumor-stroma interfaces, and none had peritumoral lymphoid aggregates. MMRD was found in 2 (2.6%) tumors; one had MLH1/PMS2 loss (MSI-high and MLH1 promoter methylation was detected) and the other had MSH2/MSH6 loss (MSI-low). Twenty (26.3%) tumors showed tumoral PD-L1 expression ≥1%. Both MMR-deficient tumors showed diffuse intratumoral stromal inflammation and tumoral PD-L1 expression ≥50%. Three of the 4 (75%) tumors with diffuse intratumoral stromal inflammation also showed tumoral PD-L1 expression ≥50%. None of the tumors without diffuse intratumoral stromal inflammation showed MMRD (P=0.021) or tumoral PD-L1 expression ≥50% (P=0.0001). We identified a strong correlation among diffuse intratumoral stromal inflammation, MMRD, and high tumoral PD-L1 expression in a small but significant subset of OCCCs. Histologic evaluation can facilitate patient selection for subsequent anti-PD-1/PD-L1 immunotherapy.
Ciliated Carcinoma of the Endometrium
Authors: Guerrieri Claudio , Anderson Patrick , Hudacko Rachel
Published: September 2020

We report a case of ciliated carcinoma of the endometrium in a 55-yr-old woman with stromal hyperthecosis of the ovaries. The patient presented with postmenopausal uterine bleeding and an endometrial curetting revealed an atypical epithelial proliferation that met the criteria for endometrioid adenocarcinoma notwithstanding an abundance of ciliated cells. Cilia were present not only within typical endometrioid glands but also within microacini of quasi-solid areas as well as inside intracytoplasmic vacuoles. The subsequent hysterectomy specimen demonstrated a well-differentiated adenocarcinoma of the endometrium with a predominance of neoplastic glands lined by ciliated epithelial cells, thus confirming the initial suspicion for ciliated carcinoma. Since the first description of ciliated adenocarcinoma of the endometrium in 1983, only a handful of additional cases have been reported in the literature. We review the spectrum of histologic presentations of this endometrial neoplasm and elaborate on its distinction from cilia-bearing mimickers and its histogenesis.
Evaluation of SWI/SNF Protein Expression by Immunohistochemistry in Ovarian Clear Cell Carcinoma
Authors: Bennett Jennifer A. , Safdar Nida , Segal Jeremy P. , Lastra Ricardo R. , Oliva Esther
Published: September 2020

Ovarian clear cell carcinomas (OCCC) are known to harbor ARID1A mutations, and several recent studies have described immunohistochemical loss of SMARCA2, SMARCA4, and SMARCB1 in a subset of tumors. We performed ARID1A, SMARCA2, SMARCA4, and SMARCB1 immunohistochemistry on 105 OCCCs to identify possible associations with clinicopathologic features and assess their prognostic value in these tumors. ARID1A, SMARCA4, and SMARCB1 were considered retained if any tumor cell nucleus stained while for SMARCA2, >5% of tumor nuclei were required to be positive. Patients had a mean age of 56 yr and tumors averaged 13 cm in size. Most patients (63%) had stage I tumors with 47% being alive and well, 41% dead from disease, 10% dead from other causes, and 3% alive with disease at last follow-up (mean 72 mo). Tumors showed an admixture of architectural patterns, but papillary was most frequent (49%). Stromal hyalinization was detected in 83% of OCCCs and a background precursor in 78%. High-grade atypia and/or oxyphilic cells were noted in 45% and 29% of tumors, respectively. All OCCCs expressed SMARCA4 and SMARCB1, but the absence of ARID1A was noted in 30% of tumors and SMARCA2 in 8%. ARID1A-retained OCCCs were associated with a dominant tubulocystic or solid pattern, but no other clinicopathologic features reached statistical significance. No switch/sucrose non-fermentable protein expression was predictive of prognosis. Additional studies with known mutational status of these proteins are warranted to better assess their prognostic utility and develop a standardized immunohistochemical scoring system.
P16, Ki67, P53, and WT1 Expression in Uterine Smooth Muscle Tumors: An Adjunct in Confirming the Diagnosis of Malignancy in Ambiguous Cases
Authors: Delgado Bertha , Dreiher Jacob , Braiman Dana , Meirovitz Mihai , Shaco-Levy Ruthy
Published: September 2020

The diagnosis of uterine smooth muscle tumors is sometimes difficult, as these tumors may show worrisome features, suspicious for but not diagnostic of malignancy. The recommended immunohistochemical panel in this setting is currently under debate. In this study, we aimed to find a panel of immunohistochemical stains that would be helpful in determining the correct diagnosis in ambiguous uterine smooth muscle tumors, with an emphasis on investigating the possible usefulness of the WT1 antibody. Uterine leiomyomas were found to be immunoreactive with WT1. Since a previous study reported on the lack of immunoreactivity of uterine leiomyosarcomas with WT1, we speculated that WT1 might be useful in this setting. We retrospectively reviewed the medical charts and slides of 91 patients: 22 with leiomyosarcoma, 15 with smooth muscle tumor of uncertain malignant potential, and 54 with leiomyoma. Immunohistochemical stains for WT1, p16, p53, and Ki67 were performed on each case. We found that immunoreactivity with p16 and Ki67 (>40% and >10% of the tumor cells, respectively) and loss of nuclear expression of WT1 (<10% of the tumor cells) were significantly more common in leiomyosarcomas (all P<0.001). Mutated p53 immunohistochemical staining pattern was significantly more prevalent in leiomyosarcomas than in leiomyomas (P<0.001). Thus, in diagnostically challenging uterine smooth muscle tumors, we recommend using an immunohistochemical panel composed of Ki67, p16, p53, and WT1. A positive result in either of the former 2 (p16 >40% and/or Ki67 >10%) has the strongest association with leiomyosarcoma (sensitivity: 95.5%, specificity=88.9%, positive predictive value=77.8%, negative predictive value=98.0%).
HMGA2 Is a Useful Marker of Vulvovaginal Aggressive Angiomyxoma But May Be Positive in Other Mesenchymal Lesions at This Site
Authors: Harkness Robert , McCluggage W. Glenn
Published: September 2020

Aggressive angiomyxoma (AA) is a rare mesenchymal neoplasm occurring almost exclusively in the vulvovaginal region and which has a wide differential diagnosis. It has previously been suggested that the nuclear transcription factor HMGA2 is a useful marker of AA, although the number of studies is limited. We investigated HMGA2 immunoreactivity in a large series (n=284) of vulvovaginal mesenchymal lesions. HMGA2 nuclear staining was classified as diffuse (≥50%), focal (<50%), or negative. Of 38 cases of AA, 26 (68%) were positive; 77% (n=20) of these exhibited diffuse staining. Of the 41 smooth muscle tumors, 18 (44%) were positive with 16 (89%) exhibiting diffuse staining. 80 fibroepithelial stromal polyps were included and 15 (19%) were positive (8 diffuse; 7 focal). Most of the fibroepithelial stromal polyps that exhibited diffuse HMGA2 immunoreactivity were large and edematous. Occasional cases of a variety of other lesions were positive, including 1 of 30 superficial myofibroblastomas and 1 of 16 angiomyofibroblastomas. Cellular angiofibromas (n=12) and superficial angiomyxomas (n=6) were always negative. Our results confirm that HMGA2 is a useful marker of AA but a significant minority of cases are negative. The marker also lacks specificity, since a high percentage of smooth muscle tumors are positive, although these typically do not bear a close morphologic resemblance to AA. A novel observation in our study is positive staining of some fibroepithelial stromal polyps, particularly when large and edematous; these are particularly likely to be confused morphologically with AA and positive staining with HMGA2 represents a significant diagnostic pitfall.
Atypical Non-neoplastic Changes in Anogenital Mammary-like Glands Accompanying Invasive Squamous Cell Carcinoma
Authors: Konstantinova Anastasia M. , Kastnerova Liubov , Michal Michal , Kazakov Dmitry V.
Published: September 2020

Long regarded as ectopic or supernumerary breast tissue, anogenital mammary-like glands (AGMLG) are now considered a normal constituent of the anogenital area. AGMLG are presumed to be the origin for various benign and malignant lesions. Changes in AGMLG compatible with usual ductal hyperplasia and atypical ductal hyperplasia considered as precursor lesions and its presence in specimens can be explained by their role in the pathogenesis of primary extramammary Paget disease. In this report, we presented four cases of invasive squamous cell carcinoma accompanied by non-neoplastic atypical changes in ductal portions of AGMLG compatible with atypical ductal hyperplasia in breast adjacent to the carcinoma. This is a reactive phenomenon similar to that seen in apocrine/eccrine glands adjacent to squamous cell carcinoma. In a limited biopsy specimen, these areas should not be mistaken for adenocarcinoma.
The O-Linked N-Acetylglucosamine Containing Epitope H (O-GlcNAcH) is Upregulated in the Trophoblastic and Downregulated in the Fibroblastic Cells in Missed Miscarriage Human Chorionic Villi With Simple Hydropic Degeneration
Authors: Nikolaou Michail A. , Drosos Yiannis , Havaki Sophia , Arvanitis Dimitrios , Sotiriou Sotirios , Vassiou Katerina , Zibis Aristeidis , Arvanitis Leonidas D.
Published: September 2020

Epitope H contains an O-linked N-acetylglucosamine (O-GlcNAcH) residue in a specific conformation and/or environment recognized by the mouse monoclonal antibody H. O-GlcNAcH is present in several types of cells and in several polypeptides, including cytokeratin 8 and vimentin, on the latter in cells under stress. In the present work, we examined the expression of the O-GlcNAcH in 60 cases of endometrial curettings from missed miscarriage cases containing normal and simple hydropic degenerated chorionic villi in each case, using monoclonal antibody H and indirect immunoperoxidase and Western blot immunoblot. In all cases examined the expression of the O-GlcNAcH was cytoplasmic as follows: (1) syncytiotrophoblastic cells showed very low expression in chorionic villi (CV) with nonhydropic degeneration (NHD) and high expression in hydropic degenerated (HD) CV; (2) cytotrophoblastic cells showed low expression in CV with NHD and high expression in HD CV; (3) fibroblastic cells showed high expression in CV with NHD and very low expression in HD CV; (4) histiocytes showed very low expression in both types of CV; (5) endothelial cells showed high expression in both types of CV. An immunoblot of CV from one case of a legal abortion from a normal first-trimester pregnancy showed 5 polypeptides with 118.5, 106.3, 85, 53, and 36.7 kD bearing the epitope H and the 53 kD corresponded to cytokeratin 8. The expression of the O-GlcNAcH is upregulated in the trophoblastic cells and downregulated in the fibroblastic cells in the HD CV in comparison to the NHD CV.
Atypical Microglandular Hyperplasia of Endocervix as the Presenting Feature of Plasminogen Deficiency
Authors: Stewart Colin J.R.
Published: September 2020

A 30-yr-old patient with no significant past medical history presented with postcoital bleeding and was found to have fibrinous pseudomembranous lesions overlying and partly in continuity with the endocervical mucosa. Histologically, these were characterized by an atypical microglandular proliferation that was associated with extensive fibrinous exudate and a prominent neutrophil polymorph infiltrate. Ligneous stromal alteration was not identified but the changes prompted hematologic review which confirmed plasminogen deficiency. A subsequent endometrial biopsy also demonstrated degenerate glands within a fibrin-rich matrix. This is the third case demonstrating an association between atypical endocervical microglandular hyperplasia and plasminogen deficiency. The diagnosis should also be considered when biopsies demonstrate exuberant fibrin exudate even if ligneous disease is not present.
Nuclear Beta-Catenin Expression in Endometrioid Intraepithelial Neoplasia (Atypical Hyperplasia) Does Not Predict Carcinoma on Subsequent Hysterectomy
Authors: Wright Martha F. , Fitzlaff Sarah , Wyeth Autumn , Zaragoza-Watkins Matthew , Podoll Mirna B. , Quick Charles M. , Watkins Jaclyn C.
Published: September 2020

Beta-catenin (BC) mutations are associated with a high risk of recurrence in otherwise low-grade, early-stage uterine endometrioid adenocarcinomas. Recent literature suggests nuclear BC expression by immunohistochemistry is highly sensitive and specific for BC mutations. The significance of BC expression in endometrioid intraepithelial neoplasia (EIN/atypical hyperplasia) and its relationship to altered differentiation patterns in EIN has yet to be fully explored. Cases meeting current diagnostic criteria for EIN based on H&E examination were obtained from 2 institutions (years 1999–2014). Patterns of altered differentiation (eg, tubal, squamous morular metaplasia, mucinous, secretory) were noted. Representative blocks were stained for BC, and expression patterns recorded. Follow-up and demographic data was obtained from the electronic medical record. Ninety-six cases were included (84 biopsies, 12 hysterectomies). BC nuclear expression was identified in 41 cases (42.7%), with 33 of 41 demonstrating foci of nonmorular BC staining. BC staining in any component of EIN was not significantly associated with the presence of carcinoma on subsequent hysterectomy (P=0.79). When restricting to nonmorular BC, the results were the same (P=0.56). Cases with tubal differentiation were significantly less likely to demonstrate nonmorular BC than cases with no specific pattern of differentiation (P<0.01). EIN frequently demonstrates BC nuclear positivity, especially in cases without tubal differentiation. BC nuclear expression in EIN does not appear to be associated with an increased likelihood of carcinoma on subsequent hysterectomy. Our results do not support routine use of BC immunohistochemistry as a prognostic biomarker in cases of EIN.
CD56 is Expressed in Uterine Smooth Muscle Tumors
Authors: Karpathiou Georgia , Chauleur Celine , Papoudou-Bai Alexandra , Dagher Sami , Peoc’h Michel
Published: September 2020

CD56 is used in gynecologic pathology, typically in the context of a neuroendocrine, sex cord or sex cord–like tumor. It has never been studied in uterine smooth muscle tumors, which can potentially enter their differential diagnosis, and thus CD56 positivity could potentially be a pitfall. Thus, the aim of this study was to explore its expression in this category of tumors. Seventy-eight uterine smooth muscle tumors, including 14 leiomyosarcomas, 46 leiomyomas and their variants, 14 smooth muscle tumors of uncertain malignant potential, and 4 intravenous leiomyomatoses were studied in regard to CD56 expression. Fifty-eight nearby myometria were also analyzed. Sixty-five (83.4%) tumors showed CD56 expression. Nearby myometrium showed CD56 expression in 15 cases (25.9%). Staining ranged from 10% to 100% of tumor or myometrial cells (median 80% and 50%, respectively). Among the tumor types, leiomyoma with bizarre nuclei, had the lowest extensive expression (P=0.01). Most uterine smooth muscle neoplasms express CD56; thus, it is not useful in attempting to discriminate from endometrial stromal or sex cord–like neoplasms.
A Case Report of Incidental Primary Leiomyosarcoma of the Fallopian Tube and a Review of the Recent Literature
Authors: Levine Adam P. , Alexander Sarah C. , Young Martin , Arora Rupali
Published: September 2020

Primary leiomyosarcoma of the fallopian tube is a very rare neoplasm with descriptions limited to case reports. We present the case of a 46-yr-old woman with a history of renal transplantation in whom a primary leiomyosarcoma of the fallopian tube was identified incidentally following hysterectomy and bilateral salpingectomy undertaken for a uterine fibroid. The tumor demonstrated classic morphological and immunohistochemical features of a leiomyosarcoma. It appeared localized to the fallopian tube and was completely resected. Adjuvant therapy was not given but active surveillance initiated. After 14 mo of follow-up, there was no evidence of disease recurrence. We review cases from the past 20 yr with a focus on management and outcomes. Given the rarity of this disease, continued publication of case reports and the creation of a centralized case registry would be of benefit.
Diagnostic Accuracy in Assessment of Depth of Myometrial Invasion in Low-grade Endometrioid Carcinoma: A 2 Center Comparative Study by MRI and Intraoperative Assessment
Authors: Nagar Rebecca , Peters Toni , Nagar Hans , McCluggage W. Glenn , Gupta Mamta
Published: September 2020

The role of lymphadenectomy in endometrial carcinomas is controversial, especially in low-grade endometrioid carcinomas. In many institutions, lymphadenectomy in the latter neoplasms is undertaken only when there is deep myometrial invasion, defined as invasion involving 50% or more of the myometrium (FIGO stage IB). There has been considerable debate as to the best modality to detect deep myometrial invasion. In Europe, preoperative magnetic resonance imaging (MRI) is the most commonly used modality while in North America, intraoperative assessment (IOA) is undertaken in most, but not all, institutions. The aim of this study was to compare the diagnostic accuracy of these 2 modalities in identifying deep myometrial invasion in low-grade endometrioid carcinomas. Two patient cohorts were studied from Belfast, UK (n=253) and Boston, USA (n=276). With respect to detecting deep myometrial invasion, MRI had a sensitivity of 72.84%, positive predictive value of 75.64% and a positive likelihood ratio of 6.59 (95% confidence interval; 4.23–10.28). IOA had a sensitivity of 78.26%, positive predictive value of 80% and a positive likelihood ratio of 20.00 (95% confidence interval; 10.35–38.63). The superior positive likelihood ratio suggests that IOA is better than MRI in determining deep myometrial invasion and the nonoverlapping 95% confidence intervals suggest this is a significant finding. However, there are significant resource implications associated with IOA and preoperative MRI carries other advantages that are discussed herein.
Impact of Ki-67 Labeling Index on Prognostic Significance of the Chemotherapy Response Score in Women With Tubo-ovarian Cancer Treated With Neoadjuvant Chemotherapy
Authors: Heayn Michelle , Skvarca Lauren B. , Zhu Li , Edwards Robert P. , Olawaiye Alexander B. , Modugno Francesmary , Elishaev Esther , Bhargava Rohit
Published: September 2020

The chemotherapy response score (CRS) proposed by Bohm and colleagues in 2015 has been validated as a reproducible method for determining histopathologic response of tubo-ovarian carcinoma to neoadjuvant chemotherapy and stratifies tumor response into 3 groups: CRS1 is defined as minimal/no response, CRS2 as moderate response, and CRS3 as marked response. Although described as a 3-tiered system, it essentially works as a 2-tiered system (CRS1/CRS2 vs. CRS3) for assessing prognosis. Here, we analyzed the prognostic value of CRS in a large cohort of tubo-ovarian carcinomas at a tertiary care center and evaluated the potential for Ki-67 labeling index on post-neoadjuvant chemotherapy samples to provide additional prognostic information. We included 170 patients with tubo-ovarian carcinoma treated with neoadjuvant chemotherapy followed by interval debulking surgery. We determined CRS for each case by reviewing slides from the interval debulking surgery resection specimen and calculated progression-free survival and overall survival. For each case with residual disease (CRS1 and CRS2, n=123, 72%), we also performed Ki-67 antibody staining and determined both average and highest Ki-67 labeling index. Consistent with prior studies, patients in our cohort with CRS1 and CRS2 showed significantly shorter progression-free survival and overall survival compared with CRS3. Further, in the subset of cases with CRS1 and CRS2, Ki-67 labeling index was predictive of OS at multiple cutoff points. An average Ki-67 labeling index of 20% (log rank test P-value: 0.0004) or a highest Ki-67 labeling index of 50% (log rank test P-value: 0.0002) could provide a practically useful cutoff. Multivariable cox proportional hazard model showed worse overall survival with both, average Ki-67 >20% (hazard ratios: 2.02, P-value: 0.00422, confidence interval: 1.25–3.28) and highest Ki-67 >50% (hazard ratios: 1.88, P-value: 0.0205, confidence interval: 1.1–3.2). We propose adding Ki-67 labeling index to CRS to provide additional prognostic separation between patients with CRS1 and CRS2.
Safety and Oncologic Outcomes of Magnetic Resonance Imaging–Guided Cryoablation of Renal Cell Carcinoma
Authors: Cazzato Roberto Luigi , De Marini Pierre , Leonard-Lorant Ian , Leclerc Loïc , Auloge Pierre , Tricard Thibault , Dalili Danoob , Garnon Julien , Lang Hervé , Gangi Afshin
Published: September 2020

Objectives

Magnetic resonance imaging guidance has been sporadically reported for renal tumor cryoablation (CA); therefore, clinical experience with this modality is still limited.

The aim of this study is to retrospectively analyze our 10-year experience with renal tumor CA performed on a 1.5 T magnetic resonance imaging unit with the intent of reporting procedural safety and oncologic outcomes.

Materials and Methods

We included 143 patients (102 men; 41 women; median age, 73 years; range, 34–91 years) with 149 tumors (median size, 2.6 cm; range, 0.6–6.0 cm), treated between 2009 and 2019. Patient, tumor, procedure, and follow-up data were collected and analyzed. The Kaplan-Meier method was used to estimate local recurrence–free (LRFS), metastasis-free (MFS), disease-free (DFS), cancer-specific, and overall (OS) survival. Univariate and multivariate models were used to identify factors associated with complications, LRFS, MFS, DFS, and OS.

Results

The overall complication rate was 10.7% (16/149 tumors), with 1 major (1/149 [0.7%]; 95% confidence interval, 0.0%–3.7%) hemorrhagic complication. Other minor complications (15/149 [10.1%]; 95% confidence interval, 0.6%–16.1%) did not include any cases of injury to nearby organs. There were no factors associated with complications.

Five-year estimates of LRFS (primary/secondary), MFS, DFS, cancer-specific survival, and OS were 82.8%/91.5%, 91.1%, 75.1%, 98.2%, and 89.6%, respectively. Increasing tumor size (hazard radio [HR], 1.8; P = 0.02) and intraparenchymal tumor location (HR, 5.6; P < 0.01) were associated with lower LRFS; increasing patient's age (HR, 0.5; P = 0.01), high tumor grade (HR, 23.3; P < 0.01) and non–clear-cell/nonpapillary histology (HR, 20.1; P < 0.01) with metastatic disease; and high tumor grade (HR, 3.2; P = 0.04) with lower DFS.

Conclusion

Magnetic resonance imaging–guided CA of renal tumors is associated with acceptable morbidity and high survival estimates at 5-year follow-up. Given the absence of complications resulting from injuries to nearby organs, further studies are required to evaluate whether the potential reduced incidence of these adverse events justifies large-scale implementation of this interventional modality.
Exercise, cancer and cardiovascular disease: what should clinicians advise?
Authors: Zimmerman Allison , Planek Maria Isabel Camara , Chu Catherine , Oyenusi Opeyemi , Paner Agne , Reding Kerryn , Skeete Jamario , Clark Brian , Okwuosa Tochi M.
Published: September 2020

Cardiovascular disease is one of the leading causes of morbidity and mortality in persons with cancer. The elevated risk is thought to derive from the combination of cardiovascular risk factors and direct cardiotoxicity from cancer therapies. Exercise may be a potential strategy to counteract these toxicities and maintain cardiovascular reserve. In this article, we review the evidence for the potential cardioprotective effects of exercise training in cancer patients before, during, and following treatment. We also propose a patient-tailored approach for the development of targeted prescriptions based on individual exercise capacity and cardiovascular reserve.
Analogous telomeres shortening and different metabolic profile: hypertension versus hypertension/type 2 diabetes mellitus comorbidity
Authors: AlDehaini Dhuha M.B. , Al-Bustan Suzanne A. , Malalla Zainab Hasan Abdulla , Ali Muhalab E. , Sater Mai , Giha Hayder A.
Published: September 2020

Background

Eukaryotes chromosomal ends are capped and protected by telomeres, which are noncoding DNA repeats synthesized by telomerase enzyme. The telomerase enzyme is a nucleoprotein encoded by TERC and TERT genes. Naturally, the length of the telomeres shortens with each cell cycle but the shortening is fastened in certain age-related diseases like hypertension (HTN) and type 2 diabetes mellitus (T2DM).

Materials and methods

Blood samples (n = 171) were obtained from Kuwaiti subjects with HTN, and HTN/T2DM comorbidity (HTN-DM) and healthy subjects. The leukocyte telomere length (LTL) was measured by SYBR green quantitative rtPCR, and plasma telomerase enzyme was measured by ELISA, in addition, three single nucleotide polymorphisms (SNPs) in telomere-related genes; TERC rs12696304GC, TERT rs2736100CA, and ACYP2 rs6713088GC were genotyped by real-time PCR.

Results

Marked LTL shortening in subjects with HTN and HTN-DM compared to healthy subjects, P = 0.043 and P < 0.001, respectively, was noticed. On the contrary, the plasma telomerase enzyme levels and minor allele frequencies and genotypes of the tested SNPs were comparable between the study groups, except for TERT (CA) genotype which was over-represented in HTN (P = 0.037). Furthermore, the comparisons between HTN and HTN-DM revealed significantly higher total cholesterol (P = 0.015) and LDL-C (P = 0.008) in HTN, while higher insulin levels (P < 001), HOMA-IR (P < 001), and BMI (P = 0.004) were observed in HTN-DM.

Conclusion

This study showed comparable LTL shortening in HTN and HTN-DM, irrespective of plasma telomerase enzyme levels or tested TERC, TERT, and ACYP2 gene polymorphisms, although HTN and HTN-DM differed in several metabolic markers. More studies are required to affirm these observations.
Hyperthyroidism in severe mitral regurgitation post mechanical mitral valve replacement: the effect on warfarin anticoagulation
Authors: Lilihata Gracia , Saputra Charles , Yaniarti Dian , Soerarso Rarsari
Published: September 2020

A 24-year-old male patient came to the emergency room with melena, gum bleeding and nosebleeds. This patient has a history of mechanical prosthetic mitral valve replacement for severe mitral regurgitation (MR) and consumed warfarin irregularly, but did not come back for regular check-up. Investigations showed greatly increased thyroid function and international normalised ratio (INR) was 15.8. Patients were diagnosed with thyroid storm and bleeding due to prolongation of INR. His hyperthyroid state might have caused increased rate of degradation of vitamin K-dependent clotting factor thereby increased sensitivity to warfarin. Concomitant acute decompensated heart failure, thrombocytopenia and hypoalbuminemia also contributed to his risk of bleeding. Treatment included anti-thyroid therapy as well as warfarin reversal therapy by stopping warfarin, low-dose intravenous vitamin K due to his mechanical prosthetic valve and fresh frozen plasma. In conclusion, hyperthyroidism could increase the response to warfarin so close monitoring is needed to balance the risk of bleeding and thromboembolism.
Facilitation of evidence implementation within a clinical fellowship program: a mixed methods study
Authors: Lizarondo Lucylynn , McArthur Alexa , Lockwood Craig , Munn Zachary
Published: September 2020

Background and aim:

Facilitation is a multifaceted process for supporting and enabling individual or group of health practitioners to implement positive changes in clinical practice. Facilitation has never been explored within the context of an educational program that integrates a practical, evidence-based implementation component, such as a clinical fellowship program (CFP). The aim of this research was to identify features of facilitation as it occurs in the JBI (formerly known as Joanna Briggs Institute) CFP that promotes the use of evidence into clinical practice.

Methods:

We used a mixed methods study design to address the objective of this study. An electronic survey was administered to clinicians of different clinical backgrounds who completed the CFP (i.e. clinical fellows). Purposively selected clinical fellows and assigned internal or external facilitators were interviewed.

Results:

Forty-three clinical fellows completed the survey and 16 individual interviews and two focus groups were conducted. Findings from the survey and interviews demonstrated that facilitation within the context of a CFP is a collaborative effort between assigned facilitators and clinical fellows. Our study showed that both assigned facilitators and clinical fellows perform facilitation activities, with assigned internal and external facilitators providing support and assistance to clinical fellows, who in turn, support the evidence implementation project within their local organization. The study also suggests that external facilitation should be tailored to the individual clinical fellow's characteristics and their previous experiences.

Conclusion:

Facilitation in an evidence-based CFP involves a partnership between clinical fellows and assigned facilitators, indicating a collaborative effort that involves a set of internal and external facilitation activities. Our study findings can guide the delivery of CFPs, particularly in identifying suitable people for the facilitator's role, which can have important implications for evidence implementation. Future research should focus on evaluating the effectiveness of these programs in improving practice and health outcomes.
The European carbon cycle response to heat and drought as seen from atmospheric CO
2
data for 1999–2018
Authors: Rödenbeck C. , Zaehle S. , Keeling R. , Heimann M.
Published: September 2020

In 2018, central and northern parts of Europe experienced heat and drought conditions over many months from spring to autumn, strongly affecting both natural ecosystems and crops. Besides their impact on nature and society, events like this can be used to study the impact of climate variations on the terrestrial carbon cycle, which is an important determinant of the future climate trajectory. Here, variations in the regional net ecosystem exchange (NEE) of CO
2
between terrestrial ecosystems and the atmosphere were quantified from measurements of atmospheric CO
2
mole fractions. Over Europe, several observational records have been maintained since at least 1999, giving us the opportunity to assess the 2018 anomaly in the context of at least two decades of variations, including the strong climate anomaly in 2003. In addition to an atmospheric inversion with temporally explicitly estimated anomalies, we use an inversion based on empirical statistical relations between anomalies in the local NEE and anomalies in local climate conditions. For our analysis period 1999–2018, we find that higher-than-usual NEE in hot and dry summers may tend to arise in Central Europe from enhanced ecosystem respiration due to the elevated temperatures, and in Southern Europe from reduced photosynthesis due to the reduced water availability. Despite concerns in the literature, the level of agreement between regression-based NEE anomalies and temporally explicitly estimated anomalies indicates that the atmospheric CO
2
measurements from the relatively dense European station network do provide information about the year-to-year variations of Europe’s carbon sources and sinks, at least in summer.

This article is part of the theme issue ‘Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale’.