bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraluminal Polypoid Metastasis of Renal Cell Carcinoma in Gallbladder Mimicking Gallbladder Polyp
Authors: Fang Xueping , Gupta Nilesh , Shen Steven S. , Tamboli Pheroze , Charnsangavej Chusilp , Rashid Asif , Wang Huamin
Published: February 2021

Context.—Metastatic renal cell carcinoma (RCC) in gallbladder is rare with only 18 cases published in the English literature.

Objectives.—To review the clinicopathologic characteristics of metastatic RCC in gallbladder and to correlate the findings with clinical outcomes.

Design.—We report 4 additional cases of intraluminal polypoid metastasis of RCC in gallbladder and reviewed all reported cases, to our knowledge, of metastatic RCC in gallbladder in the English literature.

Results.—Most of the patients (19 of 22; 86%) were men. The ages at presentation ranged from 39 to 84 years with a median age of 61.5 years. All cases showed an intraluminal polypoid/pedunculated mucosal mass mimicking a gallbladder polyp. Histologically, all cases were clear cell RCC with most of the tumors either confined to gallbladder mucosa (67%) or involved both mucosa and muscular layer (27%). The longest interval between nephrectomy and the development of gallbladder metastasis was 27 years.

Conclusions.—Metastatic clear cell RCC should be considered in the differential diagnosis of polypoid lesion of the gallbladder with clear cell morphology. Solitary metastasis of RCC in gallbladder correlated with better survival, and simple cholecystectomy for solitary metastatic RCC may provide patients with favorable long-term survival.
Revisiting Chordoma With Brachyury, a “New Age” Marker: Analysis of a Validation Study on 51 Cases
Authors: Jambhekar Nirmala A. , Rekhi Bharat , Thorat Kiran , Dikshit Rajesh , Agrawal Manish , Puri Ajay
Published: February 2021

Context.—Chordoma is a rare, notochordal tumor with a characteristic histomorphology and immunohistochemical profile. At times, it presents a diagnostic challenge, especially in small biopsies. Brachyury, a nuclear transcription factor, is a recently described immunohistochemical marker for diagnosing chordomas.

Objective.—To study the sensitivity and specificity of brachyury in diagnosing chordomas by comparing its expression in axial chordomas with nonchordomatous tumors.

Design.—Fifty-one axial chordomas, accessioned during a 10-year period, and 58 nonchordomatous tumors were subjected to brachyury staining by immunohistochemistry.

Results.—The 51 chordomas occurred in 36 men and 15 women. Sitewise, 34 cases (66.7%) occurred in the sacrococcyx, 9 (17.6%) in the spine, and 8 (15.7%) in the skull base. Histologically, 34 cases (66.7%) were classical chordomas, 13 cases (25.5%) had a dominant chondroid component, and 2 cases each (3.9%) were chondroid chordomas and dedifferentiated chordomas, respectively. Brachyury staining was positive in 46 of the 51 chordomas (90.2%) and negative in all 58 nonchordomatous tumors. The dedifferentiated area in 2 chordomas was negative for brachyury staining. Fourteen of 15 chordomas with chondroid component showed positive brachyury staining. Immunohistochemical expression of other markers, included cytokeratin (positive in 23 of 23 cases; 100%), epithelial membrane antigen (positive in 22 of 22 cases; 100%) and S100 protein (positive in 18 of 21 cases; 85.7%).

Conclusion.—Exclusive brachyury expression in more than 90% of chordomas indicates its value as a unique, specific marker with other sensitive markers like cytokeratin, epithelial membrane antigen, and/or S100 protein in substantiating a diagnosis of chordoma, including on small biopsies.
Melanocytic Lesions of the Conjunctiva
Authors: Zembowicz Artur , Mandal Rajni V. , Choopong Pitipol
Published: February 2021

Context—Melanocytic proliferations are among the most common neoplasms of the conjunctiva. They often represent challenging lesions for pathologists unfamiliar with unique histologic features of melanocytic proliferations in this location and with nomenclature used by ophthalmologists.

Objective—To comprehensively review clinical aspects, pathologic features, and management of melanocytic proliferations of the conjunctiva.

Data Sources—Review of the literature and personal experience of the authors.

Conclusions—Classification, state of the art, and practical aspects of pathology of melanocytic proliferations of the conjunctiva are discussed.
Pulmonary Lymphangioleiomyomatosis
Authors: Zhang Xuchen , Travis William D.
Published: February 2021

Lymphangioleiomyomatosis is an uncommon lung disease primarily affecting women of childbearing age. It is characterized by the progressive proliferating and infiltrating smooth musclelike cells (lymphangioleiomyomatosis cells), which lead to the cystic destruction of the lung parenchyma; obstruction of airways, blood vessels, and lymphatics; and loss of pulmonary function. Lymphangioleiomyomatosis cells coexpress smooth muscle markers (such as smooth muscle actin and desmin) and melanocytic markers (such as HMB-45, Melan-A/MART-1, and microphthalmia transcription factor). Dyspnea on exertion and recurrent pneumothorax are the most common clinical features. Somatic or genetic mutations of tumor suppressor genes tuberous sclerosis complex (TSC) 1 or TSC2 are closely related to lymphangioleiomyomatosis. The TSC1/TSC2 protein-related signaling pathways are involved in the pathogenesis and may provide novel therapeutic targets for lymphangioleiomyomatosis and diseases associated with TSC1/TSC2 dysfunction.
Neuroendocrine Tumors of the Lung: An Update
Authors: Rekhtman Natasha
Published: February 2021

Context.—The 2004 World Health Organization (WHO) classification recognizes 4 major types of lung neuroendocrine tumors: typical carcinoid, atypical carcinoid, small cell lung cancer, and large cell neuroendocrine carcinoma. Markedly different prognostic implications and treatment paradigms for these tumors underscore the importance of accurate pathologic diagnosis.

Objective.—To detail the clinical and pathologic features of lung neuroendocrine tumors, with emphasis on diagnostic criteria, differential diagnoses, and application of immunohistochemistry. The emerging evidence for the utility of Ki-67 (MIB1) in the diagnosis of lung neuroendocrine tumors, particularly in small biopsy and cytology, is emphasized.

Data Sources.—The 2004 WHO classification, other published literature, and primary material from the author's institution.

Conclusions.—The current WHO classification of neuroendocrine tumors is based on morphologic features in combination with precisely defined mitotic rate and absence or presence of necrosis. Ki-67 (MIB1) is emerging as a useful ancillary tool in the diagnosis of these tumors. Continued research efforts are needed to identify additional immunohistochemical and molecular biomarkers that can serve as ancillary diagnostic tools and as potential therapeutic targets for these diseases.
Significance of High-Risk Human Papillomavirus DNA Detection in Women 50 Years and Older With Squamous Cell Papanicolaou Test Abnormalities
Authors: Zhao Chengquan , Zhao Shuping , Heider Amer , Austin R. Marshall
Published: February 2021

Context.—Data on cytologic screening and follow-up disproportionately reflect findings from frequently screened younger women, and data from screened women 50 years and older using newer screening technologies remain limited.

Objective.—To better understand the utility of adjunctive high-risk human papillomavirus (hrHPV) testing for disease risk stratification in women 50 years and older with a range of liquid-based cytology, abnormal, squamous cell Papanicolaou test results.

Design.—Liquid-based cytology cases interpreted as high-grade squamous intraepithelial lesion (HSIL); low-grade squamous intraepithelial lesion (LSIL); atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H); and atypical squamous cells of undetermined significance (ASC-US) at Magee-Womens Hospital (Pittsburgh, Pennsylvania) were retrospectively identified for a 36-month period between July 1, 2005, and June 30, 2008, from women 50 years and older who also had hrHPV DNA test results. Histopathologic follow-up diagnoses were analyzed.

Results.—During the study period, 4855 women 50 years and older had HSIL, LSIL, ASC-H, or ASC-US Papanicolaou test results and hrHPV testing. In 89.3% of HSIL cases, 71.0% of LSIL cases, 38.9% of ASC-H cases, and 14.2% of ASC-US cases, hrHPV test results were positive. The positive predictive value of a positive hrHPV test for histopathologic cervical intraepithelial neoplasia 2/3+ detection was 90.5% with HSIL, 15% with ASC-H, 9.8% with LSIL, and 3.2% with ASC-US. A negative hrHPV test result had a 100% negative predictive value for histopathologic cervical intraepithelial neoplasia 2/3+ in both LSIL and ASC-H cases.

Conclusions.—In women 50 years and older, a positive hrHPV test result significantly increased the likelihood of follow-up histopathologic diagnoses of cervical intraepithelial neoplasia 2 /3+ in patients with HSIL, LSIL, and ASC-H Papanicolaou test results compared with women with negative hrHPV test results. No cervical intraepithelial neoplasia 2/3+ diagnoses were documented in women 50 years and older with LSIL or ASC-H Papanicolaou test results and negative hrHPV test results.
Prognostication in Thin Cutaneous Melanomas
Authors: Gimotty Phyllis A. , Guerry DuPont
Published: February 2021

Context—While most patients diagnosed with thin cutaneous melanoma will have a good prognosis, nearly 5% will die of their disease. Thin melanomas are common and approximately one-quarter of all melanoma-related deaths result from thin primary tumors. Patients with thin melanoma commonly have sentinel lymph node biopsies that are uncommonly positive.

Objective—To review the progress that has been made in the translation of prognostic and predictive biomarkers for patients with thin melanomas by focusing on the developments during the last 5 years in using measures of tumor proliferation. Given the paucity of biomarkers for patients with thin melanoma, we review some of the challenges in the development, validation, and translation of new biomarkers into clinical practice.

Data Sources—Surveillance, Epidemiology and End Results registry data, cohort data from a cancer center's program in melanoma, and focused literature review.

Conclusions—The presence of dermal mitoses improves prognostication and prediction. To optimize patient management, biomarkers reflecting biologic processes underlying tumor progression will need to be included in panels and risk models, validated, generalized, and ratified.
Differential Notch1 and Notch2 Expression and Frequent Activation of Notch Signaling in Gastric Cancers
Authors: Sun Yuan , Gao Xue , Liu Jia , Kong Qing-You , Wang Xiao-Wei , Chen Xiao-Yan , Wang Qian , Cheng Yi-Fan , Qu Xiao-Xia , Li Hong
Published: February 2021

Context.—The biologic effects of Notch1 and Notch2 vary with cancer types and their potential role(s) in gastric cancers (GCs) remains largely unknown.

Objectives.—This study aimed to address the previously mentioned issue by checking the expression of Notch1, Notch2, and Notch target gene Hes1 in GCs, premalignant gastric lesions, and noncancerous endoscopic gastric mucosa and by inhibiting Notch signal transduction in GC cells.

Design.—The status of Notch1, Notch2, and Hes1 expression in 74 GC surgical specimens, 10 endoscopic samples, and 4 human GC cell lines was evaluated by tissue microarray–based immunohistochemical staining, Western blotting, and reverse transcription-polymerase chain reaction, and the importance of Notch signaling was elucidated by treating 2 GC cell lines with 2 γ-secretase inhibitors.

Results.—Notch1 was undetectable in noncancerous gastric mucosa but was expressed with nuclear translocation in 16.7% (4 of 24) of chronic gastritis, 50.0% (9 of 18) of intestinal metaplasia, 54.2% (26 of 48) of intestinal GC, and 23.1% (6 of 26) of diffuse GC, showing distinct differences of Notch1 detection rates between either intestinal metaplasia and chronic gastritis or intestinal GCs and diffuse GCs (P  =  .03; P  =  .005, respectively). Notch2 nuclear translocation frequencies were 10.0% (1 of 10) in noncancerous endoscopic mucosa, 71.4% (30 of 42) in premalignant lesions, and 97.3% (72 of 74) in GC tissues, demonstrating a correlation of Notch2 expression with both intestinal GC and diffuse GC formation (P < .001). The rates of nuclear-Hes1 labeling were 1 of 10 among noncancerous, 42.9% premalignant, and 81.1% cancer tissues, which were closely correlated with Notch2 (P < .001) rather than Notch1 (P  =  .42) nuclear translocation. Only Notch2 was expressed accompanied with Hes1 nuclear labeling in the 4 GC cell lines established from diffuse GC cases. Inhibition of Notch signaling with γ-secretase inhibitors, L-685,458 and DAPT, prevented Hes1 nuclear translocation but neither suppressed growth nor induced cell death.

Conclusions.—This study demonstrated a close correlation of Notch2 expression with GC formation and the potential link of Notch1 upregulation with intestinal-like phenotypes of gastric lesions. Although inhibition of Notch activity failed to achieve anti-GC effects, the activated Notch signaling may reflect a potential GC risk.
Comparison of Formalin-Free Tissue Fixatives: A Proteomic Study Testing Their Application for Routine Pathology and Research
Authors: Kothmaier Hannelore , Rohrer Daniela , Stacher Elvira , Quehenberger Franz , Becker Karl-Friedrich , Popper Helmut H.
Published: February 2021

Context.—Formalin-fixed, paraffin-embedded tissue is the routine processing method for diagnostics practiced in pathology departments worldwide.

Objective.—To determine the potential value of non–cross-linking, formalin-free tissue fixation for diagnostics in pathology and proteomic investigations.

Design.—We tested 3 commercially available, formalin-free tissue fixatives—FineFIX, RCL2, and HOPE—in lung cancer specimens from 10 patients. The fixatives were evaluated for their effects on tissue morphology, protein recovery, and immunoreactivity for a selected panel of proteins differently expressed in lung cancer, using immunohistochemistry and Western blotting.

Results.—Tumor-cell analysis with hematoxylin-eosin worked equally well for all tested fixatives when compared with the standard formalin-fixed, paraffin-embedded procedure. Movat pentachrome stains showed comparable results for the different matrices and cellular proteins analyzed. The RCL2 (P  =  .01) and HOPE fixatives (P  =  .03) improved protein recovery when compared with formalin-fixed, paraffin-embedded or frozen tissues. Our data clearly show that the fixatives evaluated influenced immunoreactivity to matched, formalin-fixed, paraffin-embedded lung cancer tissue. In particular, membrane-bound proteins, such as epidermal growth factor receptor EGFR, can be detected more efficiently by immunohistochemistry and Western blotting.

Conclusion.—We have demonstrated that formalin-free fixatives have the potential in routine pathology and research to replace formalin in histomorphology and protein preservation.
Immunohistochemistry of Melanocytic Proliferations
Authors: Prieto Victor G. , Shea Christopher R.
Published: February 2021

Context.—Histologic analysis allows accurate classification of most melanocytic lesions as benign or malignant. Only in a minority of lesions is it necessary to use other techniques as an aid in the diagnosis. Among them, most authors recommend immunohistochemistry.

Objective.—To describe how to apply immunohistochemistry to particular differential diagnoses and the potential pitfalls.

Data Sources.—Personal experience and review of literature.

Conclusions.—here is no single marker, or combination thereof, that establishes an unequivocal diagnosis of melanoma or nevus. Thus it is necessary to carefully analyze the pattern of expression (patchy versus diffuse) and localization (maturation) in the context of morphologic standard features.
UroVysion, Urine Cytology, and the College of American Pathologists: Where Should We Go From Here?
Authors: Renshaw Andrew A.
Published: February 2021

UroVysion (Abbott Molecular Inc, Des Plaines, Illinois) is a US Food and Drug Administration–approved test for the diagnosis of urothelial carcinoma. Although widely used, there are a variety of different ways to evaluate and interpret the test, and questions remain about the test's cost effectiveness and reproducibility in actual clinical practice. I suggest that the College of American Pathologists has a unique opportunity to create educational programs focusing on borderline or difficult urine cytology and UroVysion samples to provide data upon which to make evidence-based decisions concerning the best use of these tests.
Immunohistochemical Expression of Neurotrophic Tyrosine Kinase Receptors 1 and 2 in Lung Carcinoma: Potential Discriminators Between Squamous and Nonsquamous Subtypes
Authors: Terry Jefferson , De Luca Alessandro , Leung Samuel , Peacock Graeme , Wang Yuzhuo , Elliot W. Mark , Huntsman David
Published: February 2021

Context.—The neurotrophic tyrosine kinase receptors NTRK1 and NTRK2 have been implicated in the pathogenesis of lung carcinomas. NTRK receptor expression has been reported in lung carcinomas; however, the clinical utility of immunohistochemical expression of these receptors is unclear.

Objective.—To compare the immunohistochemical expression profiles of NTRK1 and NTRK2 in various histologic subtypes of lung carcinomas and correlate with patient outcome.

Design.—Six hundred eighty-six unique lung cancer cases (including squamous cell carcinoma, adenocarcinoma, large cell carcinoma, small cell carcinoma, and carcinoid tumor) with clinical outcome data in tissue microarray format were immunohistochemically stained for NTRK1 and NTRK2 using commercially available antibodies, automated immunostaining, and standard protocols.

Results.—Expression of both NTRK1 and NTRK2 correlates strongly with squamous histology. NTRK1 and NTRK2 are highly specific markers (1: 92.8%, 2: 96.4%) of squamous lung carcinoma when compared with the other carcinoma subtypes, including adenocarcinoma. Positive NTRK2 staining in squamous carcinoma correlates with improved disease-specific survival (P < .001) and overall survival (P  =  .047).

Conclusions.—NTRK1 and NTRK2 are potentially useful immunohistochemical markers that may be particularly helpful in separating squamous cell carcinoma from adenocarcinoma.
Clinical, Histopathologic, and Cytologic Diagnosis of Mucosal Leishmaniasis and Literature Review
Authors: Daneshbod Yahya , Oryan Ahmad , Davarmanesh Mehdi , Shirian Sadegh , Negahban Shahrzad , Aledavood Azita , Davarpanah Mohammad Ali , Soleimanpoor Hossein , Daneshbod Khosrow
Published: February 2021

Context.—Mucosal leishmaniasis (ML) is a rare disease in the world, even in endemic areas such as Iran. Clinical, histologic, or cytologic assessment may help in the diagnosis of ML.

Objective.—To describe clinical, histologic, and cytologic findings in ML.

Design.—Review of our files showed 11 patients diagnosed with ML, of whom 7 patients had oral lesions, 1 of whom was a known patient with oral leishmaniasis with recurrence of oral lesions; 2 had laryngeal lesions; and 3 had nasal lesions. One case of laryngeal leishmaniasis was a recurrence of prior oral lesions. Cytologic smears were prepared by scraping the lesions with a scalpel or cytobrush. Histology on the biopsies was done for 7 patients. In 2 patients with nasal lesions, exfoliative cytology was made by washing the nasal cavity. Smears were both air dried and fixed in alcohol and stained.

Results.—Cytologic findings showed free Leishman-Donovan bodies, intrahistiocytic Leishman-Donovan bodies, atypical organisms, granuloma, acute and chronic inflammatory cells, histiocytes, multinucleated giant cells, mast cells, binucleated histiocytes (Reed-Sternberg–like cells), and plasma cells. In 6 of the patients, biopsy was inconclusive and in subsequent cytology the organism was detected. In 3 cases, findings from clinical and cytologic examinations were suggestive for leishmaniasis; however, with response to treatment, the diagnosis was confirmed. In 5 patients a malignant tumor was suspected because of clinical or histologic findings, but cytology helped to diagnose leishmaniasis.

Conclusions.—Clinically or histologically, ML can be mistaken for benign and malignant lesions. Scraping or exfoliative cytology is an easy, reliable, and cost-effective method for diagnosing ML. Thus, clinical, histologic, and cytologic features together may help in ML diagnosis.
Nephrogenic Adenoma: Report of a Case and Review of Morphologic Mimics
Authors: Kunju Lakshmi P.
Published: February 2021

Nephrogenic adenoma, also referred to as nephrogenic metaplasia, is an uncommon benign lesion of the urothelial tract, characterized by a circumscribed proliferation of tubules, cysts, and papillae lined by cells with low cuboidal to columnar epithelium. The diagnostic features that are useful in the recognition of this benign entity are the characteristic mixture of various architectural patterns, associated stromal edema and inflammation, hyaline sheath around tubules, eosinophilic colloidlike secretion within tubules, and lack of mitotic activity. Nephrogenic adenoma can be a significant diagnostic pitfall as certain histologic features, such as the presence of enlarged nuclei with prominent nucleoli, degenerative nuclear atypia, tiny tubules with blue mucin simulating signet ring cells, and focal invasion into superficial muscle, when taken out of context, can mimic malignancy. Herein, I report a case of nephrogenic adenoma with some worrisome histologic features and review the diagnostic criteria as well as pertinent morphologic malignant mimics of nephrogenic adenoma.
Controversies in the Diagnosis of Barrett Esophagus and Barrett-Related Dysplasia: One Pathologist's Perspective
Authors: Goldblum John R.
Published: February 2021

Context.—Pathologists frequently assess esophageal biopsy specimens to “rule out Barrett esophagus,” as well as to assess for the presence or absence of dysplasia.

Objective.—To review some of the recent controversies in the diagnosis of Barrett esophagus and Barrett-related dysplasia.

Data Sources.—Sources were the author's experience and review of the English literature from 1978 to 2009.

Conclusions.—Although goblet cells are required by the American College of Gastroenterology to confirm a diagnosis of Barrett esophagus, this definition might expand to include columnar-lined esophagus without goblet cells. The recognition of dysplasia in Barrett esophagus remains a difficult task for the surgical pathologist, with difficulties in distinguishing reactive epithelium from dysplasia, low-grade dysplasia from high-grade dysplasia, and even high-grade dysplasia from intramucosal adenocarcinoma.
Multiparameter Flow Cytometry in the Diagnosis and Management of Acute Leukemia
Authors: Peters John M. , Ansari M. Qasim
Published: February 2021

Context—Timely and accurate diagnosis of hematologic malignancies is crucial to appropriate clinical management. Acute leukemias are a diverse group of malignancies with a range of clinical presentations, prognoses, and preferred treatment protocols. Historical classification systems relied predominantly on morphologic and cytochemical features, but currently, immunophenotypic, cytogenetic, and molecular data are incorporated to define clinically relevant diagnostic categories. Multiparameter flow cytometry provides rapid and detailed determination of antigen expression profiles in acute leukemias which, in conjunction with morphologic assessment, often suggests a definitive diagnosis or a narrow differential. Many recurrent molecular or cytogenetic aberrations are associated with distinct immunophenotypic features, and therefore flow cytometry is an important tool to direct further testing. In addition, detection of specific antigens may have prognostic or therapeutic implications even within a single acute leukemia subtype. After initial diagnosis, a leukemia's immunophenotypic fingerprint provides a useful reference to monitor response to therapy, minimal residual disease, and recurrence.

Objective—To provide an overview of the application of flow cytometric immunophenotyping to the diagnosis and management of acute leukemias, including salient features of those entities described in the 2008 World Health Organization classification.

Data Sources—Published articles pertaining to flow cytometry, acute leukemia classification, and experiences of a reference flow cytometry laboratory.

Conclusion—Immunophenotypic evaluation is essential to accurate diagnosis and classification of acute leukemia. Multiparameter flow cytometry provides a rapid and effective means to collect this information, as well as providing prognostic information and a modality for minimal residual disease evaluation.
Estrogen Receptor β
Authors: Younes Mamoun , Honma Naoko
Published: February 2021

Context—A new class of estrogen receptors was discovered in 1996 and named estrogen receptor β (ER-B); the traditional estrogen receptor, which until a little more than 10 years ago was thought of as the only estrogen receptor in existence, is now called estrogen receptor α. Estrogen receptor β has at least 5 isoforms, which may have different functions and have different tissue distribution. The significance of ER-B expression in tumors was first demonstrated in breast cancer, with several studies demonstrating that women with ER-B–positive breast cancers treated with adjuvant tamoxifen have better survival, independent of estrogen receptor α expression. Pathologists need to be more aware of this increasingly important protein, as it will soon find its way into routine clinical practice.

Objective—To provide pathologists with a concise review of ER-B, with special emphasis on current and potential clinical relevance.

Data Sources—A search of the English literature in PubMed (National Library of Medicine, Bethesda, Maryland) for articles with titles including “estrogen receptor beta,” with emphasis on “immunohistochemistry.” Abstracts were reviewed, and selected articles were used as the basis for writing this review, mostly based on their relevance to pathology.

Conclusions—Estrogen receptor β and its isoforms have wider tissue distribution, including the gastrointestinal tract, lung, and brain, than the traditional estrogen receptor, now called estrogen receptor α. Estrogen receptor β expression in breast cancer is associated with favorable outcome in women treated with adjuvant tamoxifen, even in tumors negative for estrogen receptor α. The clinical significance of ER-B expression in tumors other than breast is currently under investigation.
HER2: Biology, Detection, and Clinical Implications
Authors: Gutierrez Carolina , Schiff Rachel
Published: February 2021

Context—HER2 is a membrane tyrosine kinase and oncogene that is overexpressed and gene amplified in about 20% of breast cancers. When activated it provides the cell with potent proliferative and antiapoptosis signals and it is the major driver of tumor development and progression for this subset of breast cancer. When shown to be overexpressed or amplified by appropriate methods, HER2 is a valuable treatment target.

Objectives—To review the basic biology of the HER2 signaling network, to discuss various approved methods for its detection in clinical specimens, and to describe the impressive results of therapies targeting HER2.

Data Sources—Selected literature searchable on PubMed as well as older studies revealed by the literature review were reviewed.

Conclusion—HER2 is an important member of a complex signaling network and when gene amplified, it results in an aggressive subtype of breast cancer. Patients with tumors found to overexpress HER2 protein or to be amplified for the gene are candidates for therapy that significantly reduces mortality.
Update on Precursor and Early Lesions of Hepatocellular Carcinomas
Authors: Park Young Nyun
Published: February 2021

Context.—There is increasing evidence to support a multistep model of the process of human hepatocarcinogenesis. Precursor lesions are characterized by the appearance of dysplastic lesions in the form of microscopic dysplastic foci and macroscopic dysplastic nodules. There are 2 types of small hepatocellular carcinoma (HCC) (≤2 cm in diameter): (1) early HCC with an indistinct margin and (2) progressed HCC with a distinct margin. Pathologic diagnostic criteria for early HCC have recently been set up based on a consensus between Eastern and Western pathologists.

Objective.—To review the nomenclature, pathology, and biomarkers of precursor and early lesions of HCC.

Data Sources.—Literature review and illustrations from case materials were used.

Conclusions.—Dysplastic foci are composed of large and small cell changes. Small cell change is considered to be a more advanced precursor lesion than large cell change, and large cell change is a rather heterogeneous lesion that may represent both reactive change and true dysplasia. Dysplastic nodules can be categorized as low or high grade according to the degree of atypia. High-grade dysplastic nodules have been reported to show molecular changes similar to HCC and have a high risk of malignant transformation. Early HCC, which may correspond to microinvasive carcinomas of other organs, is a well-differentiated HCC, and differential diagnosis between early HCC and high-grade dysplastic nodule is difficult. Identification of stromal invasion and application of a panel of markers (glypican-3, heat shock protein 70, and glutamine synthetase) is helpful for diagnosis of early HCC. Detection of precursor lesions of HCC is important in recognizing patients with higher risk of developing HCC, and diagnosis of early HCC can improve patient survival by allowing for early and adequate treatment.
Molecular Diagnostics in Urologic Malignancies: A Work in Progress
Authors: Netto George J.
Published: February 2021

Context.—Molecular diagnostic applications are now an integral part of the management algorithms of several solid tumors, such as breast, colon, and lung. In stark contrast, the current clinical management of urologic malignancies is lagging behind. Clinically robust molecular tests that can identify patients who are more likely to respond to a given targeted agent or even those in need of a more aggressive treatment based on well-validated molecular prognosticators are still lacking. Several promising biomarkers for detection, prognosis, and targeted therapeutics are being evaluated.

Objective.—To discuss candidate biomarkers that may soon make the transition to clinical assay for patients in urologic oncology.

Data Sources.—Selected original articles published in the PubMed service of the US National Library of Medicine.

Conclusions.—Recent understanding of the complex molecular alterations involved in the development and progression of urologic malignancies is yielding novel diagnostic and prognostic molecular tools and opening the doors for experimental targeted therapies in these prevalent, frequently lethal solid tumors.
“A random system”
Authors: Lønning Moa Nyamwathi , Laupstad Inga , Bringedal Houge Anette , Aasnes Ann Evy
Published: February 2021

Introduction: This article addresses the provision of rehabilitation services for torture victims with a refugee background in Norway. It engages the topic from the outset of relevant rehabilitation rights and duties, presenting the organisation of rehabilitation services within the Norwegian health care system, and exploring the challenges and opportunities professionals see and experience as they seek to provide adequate treatment and rehabilitation for torture victims.

Methods and material: The article is based on qualitative interviews with 46 experts and practitioners that contribute to or otherwise focus on treatment and rehabilitation for torture victims in Norway, conducted between March and August 2019. Findings and discussion: Rehabilitation services for torture victims in Norway are fragmented, and the resulting practice is highly person dependent. Public services are characterised by insufficient knowledge about torture injuries and rehabilitation and a generalised lack of familiarity with international protocols for identification and documentation of torture. Moreover, the quality of rehabilitation services suffers from a lack of coordination and inclusion of actors that can contribute to comprehensive rehabilitation processes.

Conclusion: Individuals with a refugee background are far from guaranteed adequate rehabilitation for torture-related injuries in Norway. Rehabilitation services suffer from the absence of a systematic approach to identification and documentation, and an unclear division of responsibilities. Three recommendations are proposed in order to ensure minimum standards in rehabilitation services for this group: 1) developing and implementing a national plan of action on torture rehabilitation; 2) knowledge and capacity-building within relevant educational programmes, the national health services and other relevant public sector services; and 3) strengthening and institutionalising interdisciplinary communities of practice with specialised expertise on the topic at all relevant levels.
Effect of incubation temperature and substrate moisture on embryonic development, hatchling phenotypes and post-hatching growth in the Reeves’ Turtle, Mauremys reevesii
Authors: Wei Yufeng , Gao Yangchun , Cao Dainan , Ge Yan , Shi Haitao , Gong Shiping
Published: February 2021

Background

Reeves’ Turtles (Mauremys reevesii) are economically important in aquaculture in China. Understanding the effects of incubation temperature and substrate moisture on embryos and hatchlings is of great significance for improving the artificial culture of M. reevesii. However, available studies have not yet determined the thermal and hydric optima for M. reevesii eggs, and the potential interaction between the two factors.

Methods

In this study, eggs of M. reevesii were incubated at five temperature levels (23, 26, 29, 32 and 35 °C, fluctuation range ± 0.5 °C). In each temperature level, there were three substrate moisture levels (1:0.5, 1:0.9 and 1:1.2, weight ratio of vermiculite to water). Thus, a total of 15 combinations of temperature and moisture were used to examine the effects of incubation temperature and substrate moisture on incubation duration, hatching success, hatchling phenotypes, post-hatching growth and hatchling survival.

Results

Substrate moisture did not significantly affect most development parameters (except incubation duration and carapace width of hatchlings). Eggs incubated at low moisture level (1:0.5) had a longer incubation duration and produced hatchlings with smaller carapace widths than those incubated at medium (1:0.9) or high (1:1.2) moisture levels. Incubation temperature had a significant effect on incubation duration, hatching success, hatchling phenotypes and hatchling survival. Incubation duration decreased as incubation temperature increased. Eggs incubated at 23, 26 and 29 °C showed higher hatching success than those incubated at 32 and 35 °C. Hatchlings incubated at 32 °C were smaller in body size and mass than those incubated at 23, 26 and 29 °C. At 12 months of age, incubation temperature had no long-lasting effect on body mass, but hatchlings incubated at 23 and 35 °C had lower survival rates than those incubated at 26, 29 and 32 °C. For the development of embryos and hatchlings, the interaction between incubation temperature and substrate moisture was not significant.

Conclusions

Our results indicate that incubation temperature has a significant influence on the development of embryos and hatchlings of M. reevesii, while substrate moisture only significantly affects the incubation duration and carapace width of hatchlings. The combination of an incubation temperature of 29 ± 0.5 °C and a substrate moisture level of 1:1.2 represented optimal incubation conditions in this experiment. Such incubation conditions are helpful in obtaining higher hatching success, shorter incubation duration and higher survival rates for this aquaculture species.
RNA sequencing-based exploration of the effects of far-red light on lncRNAs involved in the shade-avoidance response ofD. officinale
Authors: Li Hansheng , Ye Wei , Wang Yaqian , Chen Xiaohui , Fang Yan , Sun Gang
Published: February 2021

Dendrobium officinale(D. officinale) is a valuable medicinal plant with a low natural survival rate, and its shade-avoidance response to far-red light is as an important strategy used by the plant to improve its production efficiency. However, the lncRNAs that play roles in the shade-avoidance response ofD. officinalehave not yet been investigated. This study found that an appropriate proportion of far-red light can have several effects, including increasing the leaf area and accelerating stem elongation, inD. officinale. The effects of different far-red light treatments onD. officinalewere analysed by RNA sequencing technology, and a total of 69 and 78 lncRNAs were differentially expressed in experimental group 1 (FR1) versus the control group (CK) (FR1-CK) and in experimental group 4 (FR4) versus the CK (FR4-CK), respectively. According to GO and KEGG analyses, most of the differentially expressed lncRNA targets are involved in the membrane, some metabolic pathways, hormone signal transduction, and O-methyltransferase activity, among other functions. Physiological and biochemical analyses showed that far-red light promoted the accumulation of flavonoids, alkaloids, carotenoids and polysaccharides inD. officinale. The effect of far-red light onD. officinalemight be closely related to the cell membrane and Ca2+transduction. Based on a Cytoscape analysis and previous research, this study also found that MSTRG.38867.1, MSTRG.69319.1, and MSTRG.66273.1, among other components, might participate in the far-red light signalling network through their targets and thus regulate the shade-avoidance response ofD. officinale. These findings will provide new insights into the shade-avoidance response ofD. officinale.
Prognostic implications of cell division cycle protein 45 expression in hepatocellular carcinoma
Authors: Yang Chen , Xie shufang , Wu Yi , Ru Guoqing , He Xianglei , Pan Hong-yin , Wang Shibing , Tong Xiangmin
Published: February 2021

Background

The overall prognosis of hepatocellular carcinoma (HCC) is poor and novel prognostic biomarkers might better monitor the progression of HCC. Cell division cycle protein 45 (CDC45) plays a key role in DNA replication and considered to be involved in tumorigenesis. This study investigated CDC45 expression in tumour tissues and defined its prognostic value in HCC patients.

Methods

We used immunohistochemistry (IHC) staining to examine the expression of CDC45 in tumour tissue specimens and compare them with adjacent normal tissue specimens using a constructed tissue microarray (TMA) and analyzed how clinical features are related to HCC prognosis. Functional enrichment analyses were used to describe significantly involved hallmark pathways of differentially expressed genes (DEGs, which were screened out according to the high or low expression of CDC45 in tumour tissues).

Results

Our findings showed that the proteome expression of CDC45 was evidently downregulated in HCC tissues compared with matched normal tissues (P < 0.0001). Although we did not find any differences in terms of vascular invasion, metastasis, lymphatic infiltration, or Edmondson grade between patients with high and low CDC45 expression, low CDC45 expression was significantly correlated with microvascular invasion (P = 0.046). Multivariate analysis indicated that CDC45 expression (P = 0.035) was an independent prognostic factor for the overall survival (OS) rate of HCC patients. Patients with CDC45 expression was positively correlated with OS rates among HCC patients (P < 0.05). Functional annotations indicated that CDC45 is involved in the most significant pathways, including the cell cycle, DNA replication, chemical carcinogenesis and drug metabolism–cytochrome P450 pathways.

Discussion

Our findings showed that low proteomic level of CDC45 was associated with a poor prognosis in HCC patients, indicating that CDC45 might be a novel prognostic marker.
Evaluation of Efficacy and Safety of Age-Based Intrathecal Dosing of 0.5% Hyperbaric Bupivacaine in the Paediatric Age Group
Authors: Srinivasan Parthasarathy , Saravanan Balachandar , Kulandayan Indu , Thambidurai Senthilkumar , Mahalakshmi VN
Published: February 2021

Introduction: Spinal anaesthesia in the paediatric population is a safe and reliable method of anaesthesia for infraumbilical surgical procedures. As there is greater variation in intrathecal dosing using a conventional weight-based schedule, a prospective cohort study was designed to administer an age-based intrathecal dosing schedule using 0.5% hyperbaric bupivacaine for infraumbilical surgeries in paediatric patients. Aim: To find the efficacy of age-based intrathecal dosing in terms of level of sensory blockade, success rate and adequacy of blockade for infraumbilical surgery in the paediatric age group. Materials and Methods: One hundred and thirty paediatric patients, aged between 2-12 years, posted for elective infraumbilical surgeries were given spinal anaesthesia at a dose of Age/5 (Partha formula) using 0.5% hyperbaric bupivacaine. Sedation during the procedure was provided using a combination of effective doses of pentazocine, midazolam, and atropine. The number of attempts, the success rate, the level of sensory blockade, the duration of anaesthesia and cardio-respiratory complications if any were noted. Results: The mean age of the children was 8±2.55 years. The mean dose of 0.5% hyperbaric bupivacaine used in this study was 8±2.55 milligrams. The desired sensory level of T10 was achieved in the first attempt in all the cases (100%) within 10 minutes of the subarachnoid block. The mean duration of anaesthesia was 73.42±18.6 minutes. In all the patients, the surgical procedures were completed within this anaesthetic time and none of the cases had any conversion to general anaesthesia. No complications were found in any of the patients. Conclusion: Administration of intrathecal dosing of 0.5% hyperbaric bupivacaine using Partha formula (Age/5) is a safe and successful method to provide subarachnoid blockade for infraumbilical surgeries in the Indian paediatric population.
Morel-Lavallée Lesions of Lower Extremity: A Case Series in a Tertiary Centre
Authors: Pandey Himanshu , Kumar Manish , Chhikara Rakhi , Kaushik Rohit , Kumar Lalit
Published: February 2021

Morel Lavallée lesions (ML lesions) are a rare degloving type of injury occurring after blunt trauma, usually in the peritrochanteric region and resulting into a progressive subcutaneous swelling. The current case series includes three patients with a history of trauma and development of rapidly increasing fluctuant soft tissue swelling during a time period of 18 months. Though these lesions are typically described in peritrochanteric region, two cases were encountered in the knee region. ML lesions were diagnosed precisely using Ultrasound (USG) and Magnetic Resonance Imaging (MRI) modalities and were managed accordingly. Classification of these lesions is paramount to enhance patient outcome and reduce complications.
Nerica Rice Technology Acquisition through Community Agriculture Development Project in Semi Arid Lands (CADSAL) of Kerio Valley, Kenya
Authors: Lagat Rael J. , Bunyatta David , Rop Nicholas
Published: February 2021

The aim of Community Agriculture Development Project in Semi-Arid Lands (CADSAL) in Kerio valley was to increase agricultural production in the project area and it used Community Participatory Extension (CPE) approach. A survey methodology was utilized in the study with target population of 480 small-scale farmers who interacted with the project in Kerio valley locations. The objective of the study was to determine and compare the level of performance between the CADSAL participants and non-CADSAL participants in knowledge acquired in NERICA technologies in Kerio Valley of Elgeyo Marakwet County, Kenya. A sample of 160 comprising 80 CADSAL-Participants and 80 Non-CADSAL participants was chosen using simple random sampling.  A structured questionnaire was administered through personal interviews to the respondents at their homes. Descriptive statistics was used to compute percentages, means and standard deviations. Inferential statistics was used which included multiple linear regression and t-test to test the hypothesis at α = 0.05. Data was analyzed using Statistical Package for SocialSciences (SPSS) Version 24.0. The result indicated positive acquisition of NERICA technologies by the community using community participatory extension approach. The t-test p-value of less than 0.05 was achieved upon analysis of data which led to rejection of all the null hypothesis. This means further that community extension approach was key in enhancing the level of acquisition of technology by the farmers and hence extension agents need to utilize participatory approach. The study outcome therefore encourages Community participation in the projects meant to increase knowledge of food production in order to increase food production, accessibility and income both in productivity and diversity of production hence sustainability.
The Effects of Social Media on Pharmacy Students’ Academic Performances
Authors: Ahmed Nehad J. , Alrawili Abdulrahman S. , Alkhawaja Faisal Z.
Published: February 2021

Background: The use of social media by students helps to have access to basic information as quick as possible but numerous universities and schools around the world restrict the access to social networks within its buildings to help students to concentrate on their studies.

Aim: The aim of this article is to assess the impact of social media on academic performance of pharmacy students.

Methodology: The present study includes gathering data from students through a survey research design to determine the effect of social media usage on their academic performance. The survey was adapted from a previous study and after that it is converted to online Google Form.

Results: Most of the participants in the present study said that their academic achievement is excellent (41.67%) or very good (41.67%). The majority of the students agree that the use of social media is useful in educational institutions, social media can be used to arrange group discussions with the experts and that it can be used to fix an appointment with other subject experts. The majority of the students also agree that they can receive announcements from lecturers and faculty using social media.

Conclusion: The majority of the students feel that social media affect their academic performance positively and about half of them feel that social media affect their performance negatively. It is important to increase their awareness about the importance of regulating social media usage.