Histological Differentiation Research Articles

A retrospective analysis of 32 small and well-differentiated rectal neuroendocrine tumors with regional or distant metastasis.

Rectal neuroendocrine neoplasms (NENs) are a group of rare and heterogeneous diseases and are classified as well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) based on histological differentiation. The patients were followed up with a median period of 32.5 (range 2-123) months and no patients were lost to follow-up. The median PFS time could not be obtained, as only less than half of the patients suffered tumor progression by the end of follow-up. The 1-year and 3-year PFS rates were 73.5% and 69.2%, respectively. The median OS was 86 months in the entire cohort. The 1-year and 3-year OS rates were 100% and 96.0%, respectively.

Hsa_circ_0067514 suppresses gastric cancer progression and glycolysis via miR-654-3p/LATS2 axis.

Gastric cancer is the third most frequent cancer with high prevalence and mortality globally. Circular RNAs (circRNAs) play a key role in cancer regulation, including gastric cancer. Nevertheless, only a few circRNAs have been well elucidated in gastric cancer. Hence, we investigated the action of circ_0067514 on gastric cancer and clarified the underlying mechanism. Here, we found that circ_0067514 was decreased in gastric cancer patients and cancer cells. The circ_0067514 expression was correlated with gastric cancer overall survival, lymph node metastasis, tumor, node, metastasis (TNM) stage, and histological differentiation. Overexpression of circ_0067514 blocked proliferation, invasion, and glycolysis of gastric cancer cells. Besides, circ_0067514 regulated large tumor suppressor kinase 2 (LATS2) expression by absorbing microRNA (miR)-654-3p. Furthermore, circ_0067514 modulated gastric cancer aggressive behaviors and glycolysis via miR-654-3p/LATS2 axis. Moreover, circ_0067514 constrained tumor growth in vivo. Together, this study showed that circ_0067514 suppressed gastric cancer aggressive development and glycolysis via miR-654-3p/LATS2 axis, making circ_0067514 a valuable target for preventing gastric cancer progression.

Immunohistochemical expression of paxillin in potentially malignant disorders and squamous cell carcinoma patients.

Cell adhesion molecules are essential to maintain the integrity of stratified squamous epithelium but their expression has to be dynamic to aid the mobility and turnover of cells. Paxillin is one such multi-domain protein which integrates numerous signals from cell surface receptors, integrins and growth factors. It thus functions as a regulator of various physiological and pathological processes including tissue remodeling, cell motility, gene expression, matrix organization, cell proliferation, metastasis and survival. Hence, the assessment of paxillin expression in normal control, potentially malignant disorders and oral squamous cell carcinoma patients was carried out. The present retrospective study comprised of 20 each clinically and histologically confirmed case of normal control, potentially malignant disorders, and oral squamous cell carcinomas. All the slides were stained immunohistochemically using Paxillin antibody. The localization, staining intensity and percentage of positivity for paxillin expression was statistically significant among normal control and potentially malignant disorders, whereas oral squamous cell carcinoma showed a non-significant difference. Upon comparison of histopathological grading of potentially malignant disorders, mild versus severe and moderate versus severe epithelial dysplasia showed a statistical significant difference among all the parameters of paxillin expression. However, WDSCC & MDSCC a statistically significant difference among localization and staining intensity of paxillin. Paxillin may play an important role in pathogenesis of oral squamous cell carcinoma by altering the adhesive properties of the tumor cells interacting with the extracellular matrix which in turn affects their invasive behavior and histologic differentiation.

Vimentin immunoexpression and its prognostic activity in colon cancer among Caucasian patients.

IntroductionIt is generally accepted that colon cancer is the most commonly diagnosed gastrointestinal cancer and a major public health problem. As revealed by studies, the clinical outcomes of patients, especially those with lymph node-positive status, are still unsatisfactory.AimThe current study investigated the expression of vimentin protein in colon adenocarcinoma samples from proximal and distal parts of the colon to assess its prognostic significance by correlating its immunohistochemical expression with the clinicopathological variables and survival of Caucasian patients.Material and methodsTo investigate the clinicopathological and prognostic roles of vimentin expression, the immunohistochemical analysis was performed in colon cancer tumour samples and adjacent non- pathological mucosa. As revealed, the level of vimentin immunohistochemical reactivity correlated with the grade of the histological differentiation (H [2.97] = 37.949; p < 0.001).ResultsThe Kaplan-Meier survival analysis showed that the overall survival rate in the group of patients with low vimentin immunoreactivity was significantly greater than that for patients with a moderate or strong level of vimentin protein expression. Multivariate analysis demonstrated that the grade of tumour differentiation (HR = 2.150; 95% CI: 1.380–3.349, p = 0.001) and vimentin expression (HR = 3.901; 95% CI: 2.436–6.247, p < 0.001) were independent risk factors for worse survival.

Prognostic significance of Notch3 immunoreactivity patterns in Caucasian colon adenocarcinoma patients

IntroductionColon cancer is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still not satisfactory.AimTo investigate the prognostic role of Notch3, an immunohistochemical study was performed on samples of colon adenocarcinoma tissues and adjacent non-pathological mucosa in Caucasian patients.Material and methodsParaffin-embedded colon adenocarcinoma samples were assessed immunohistochemically for Notch3 protein. Connections between Notch3 immunoexpression and clinicopathological factors including the 5-year overall survival (OS) were evaluated.ResultsThe level of the Notch3 immunohistochemical reactivity was correlated with the grade of the histological differentiation (p < 0.001). A strong expression of Notch3 protein was detected more frequently in patients with G3 tumours than in patients with G1 tumours. Moreover, the significant difference was also detected between the patients with G1 tumour and those with G2. In the G2 patients a strong reactivity was described more frequently. The Kaplan-Meier survival analysis showed that the overall survival rate in the group of patients with a low expression level of Notch3 was significantly greater than that for patients with a moderate or strong level of Notch3 immunoreactivity (p < 0.001). A multivariate analysis demonstrated that the grade of tumour differentiation (p = 0.001) and Notch3 expression (p < 0.001) were independent risk factors for worse survival.ConclusionsThe high level of Notch3 immunoexpression was demonstrated to be associated with malignancy-related clinicopathological factors and 5-year overall survival of patients.

Use of Computed Tomography-Guided Percutaneous Biopsy of Invasive Non-Mucinous Lung Adenocarcinoma to Predict the Degree of Histological Differentiation.

Background:The International Association for the Study of Lung Cancer (IASLC) published a grading system for invasive pulmonary adenocarcinoma that is closely associated with prognosis. This study aimed to investigate the accuracy of computed tomography (CT)-guided biopsy specimen grading and surgery-guided grading systems for detecting invasive non-mucinous lung adenocarcinoma and to determine whether CT-guided biopsy can predict the degree of histological differentiation.Methods:In total, 130 patients with invasive non-mucinous lung adenocarcinoma who underwent CT-guided biopsy before surgical excision were retrospectively studied. Biopsy and surgical specimen pathologies were compared. Grading was performed according to different subtypes proposed by the International Association for the Study of Lung Cancer. Sensitivity, specificity, positive and negative predictive values (PPV/NPV), and accuracy were calculated for each subtype and grade.Results:The concordance rates of biopsy and surgical pathology subtypes and grades were 73.1% and 72.3%, respectively. Sensitivity, specificity, PPV, NPV, and accuracy of grade 3 were 54.8%, 100%, 100%, 87.6%, and 89.2%, respectively. Pathology grades were primarily discrepant with respect to two aspects of biopsy and surgical samples in the same patient. First, the biopsy and surgical specimen pathology findings indicated lepidic and acinar subtypes as the main subtypes in the same patient, respectively. Second, biopsy specimen histology did not find solid types; however, >20% of solid subtypes were identified in surgical pathology samples in the same patient.Conclusions:The preoperative CT-guided biopsy specimen grading system showed relatively high accuracy and could predict the prognosis of invasive non-mucinous lung adenocarcinoma.

Lung neuroendocrine tumors: A systematic literature review (Review).

Neuroendocrine tumors (NETs) can have multiple localizations in the human body however, most often, it appears in the in thorax at tracheobronchial tree and the thymus. NETs are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells, with the lung being the second target organ after the gastrointestinal tract. These rare tumors are usually asymptomatic and non-functional with little information regarding incidence in the specialty literature. The main purpose of this review, was the analysis of the available literature in all aspects while mainly focusing on molecular diagnosis data and secondly, by using this molecular landscape to establish a differentiation of lung neuroendocrine tumors (LNETs). By analyzing the literature, new data were revealed regarding histological evaluation, genetic aberrations, prognosis depending on the type of LNET and therapeutic options that derive from these. Efficient management of these tumors is essential in the handling of symptoms and increase in life expectancy, especially in patients with functional tumors. Histological differentiation of LNETs is important in establishing proper therapeutic options and prognosis. Combined types of LNETs remain a controversial topic of discussion regarding diagnosis and treatment, a topic on which further studies are required in order to improve diagnosis in this group of tumors with heterogenous malignancy.

LYAR promotes the proliferation of non-small cell lung cancer and is associated with poor prognosis.

The aim of the study was to investigate the clinical significance of Ly-1 antibody reactive clone (LYAR) in non-small-cell lung cancer (NSCLC). The expressions of LYAR at the protein level in representative paired NSCLC tumor tissues and adjacent non-tumor tissues were measured by Western blot and immunohistochemistry. Kaplan-Meier method was used to calculate the survival curve of patients with NSCLC. Cell Counting Kit-8 assay and flow cytometry were used to estimate the cell proliferation and cell cycle, respectively. Terminal-deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was performed to detect cell apoptosis. LYAR was dramatically overexpressed in NSCLC tissues which were closely related to the survival of patients with NSCLC. In clinical studies, the expression of LYAR was related to the clinical stage, histological differentiation, and Ki-67 expression. A positive correlation was found between LYAR and Ki-67 expression by Spearman's correlation test. After serum starvation for 72 h, serum re-addition significantly increased the expression of LYAR, PCNA, and Cyclin A and promoted the cell cycle progression. LYAR knockdown inhibited the proliferation and induced the G0/G1 cell cycle arrest and apoptosis of A549 cells. The present study revealed the clinical significance of LYAR in NSCLC. LYAR might serve as a tumor promoter in NSCLC progression by promoting the proliferation and inhibiting the apoptosis of NSCLC cells. Inhibiting the expression of LYAR was considered as a potential novel therapeutic strategy for NSCLC.

SCANNING ELECTRON MICROSCOPY OF INVASIVE DUCTAL BREAST CANCER

Aim. Establishing the surface characteristics of ductal breast cancer of different degree of differentiation and different histological structure of the invasive component in scanning electron microscopy.&#x0D; Material and Methods. The results of the study of invasive ductal breast cancer using light and scanning electron microscopy were analyzed. The degree of malignancy was determined according to a modified scheme of P. Scarff, H. Bloom and W. Richardson. Electron microscopic features of the cell surface of invasive ductal breast cancer during this study were compared in each case with its histological structure and degree of malignancy G.&#x0D; Results and Discussion. Histologically, tubular, trabecular, solid, alveolar structures and discrete (single) groups of tumor cells were diagnosed in the infiltrative component of invasive ductal breast carcinoma. In terms of the surface configuration of tumor cells, we have identified three cell variants. The first variant was characterized by the presence in most tumor cells numerous asymmetric microvilli with diffuse or focal distribution on the cell surface and was prevailed in the tubular structures of the infiltrative component of ductal breast carcinoma of G1 grade (p&lt;0,05). The second variant of the surface configuration was characterized by a small number of asymmetric microvilli scattered throughout the cell surface and was diagnosed in a solid and trabecular invasive component of malignancies G2 and G3 grades. The third variant was characterized by the absence of microvilli on the surface in most tumor cells and was prevailed in the alveolar structures of the invasive component of G2 and G3 grades. It was found that the decrease in the grade of histological differentiation of invasive ductal breast cancer is associated with a decrease or absence of asymmetric microvilli on the cell surface. Tumors classified as G2 showed a wide range of surface configurations of cancer cells; in 75% [27,96-99,89] of cases G3 carcinoma was characterized by the absence of microvilli on the surface in most tumor cells, i.e., there was a III variant surface configuration of cells.&#x0D; Conclusions. Scanning electron microscopy makes it possible to provide information in a nanometer scale about the surface features of tumor cells, and the identification of phenotype features between tumor cells can be prognostically important in the course of breast cancer.

A Study on the Clinicopathological Profile of the Cases of Colorectal Carcinoma

Aim: To assess the clinicopathological details of patients with colorectal cancer in a tertiary care centre in India and compare it other studies reported in the literature.&#x0D; Study Design: This is a retrospective study conducted on all the patients who were admitted in the period of 2017 to 2020.&#x0D; Place and Duration of Study: Department of Pathology, Saveetha Medical College, Thandalam, Chennai. The data was processed and the manuscript was prepared between June 2020 and January 2021.&#x0D; Methodology: Patient details were collected from the histopathology records and the parameters studied were age, gender, tumour site, histological type, differentiation and tumour stage of the colorectal carcinoma. The sampling was done using the complete enumerate sampling method. The patients diagnosed histopathologically as colorectal carcinoma were included in our study.&#x0D; Results: A total of 51 patients had been admitted in the years 2017, 2018, and 2019 in our institute. There was a female predominance among the patients. The mean age of the patients was lesser than the mean age of colorectal cancer cases in other studies which have been reported in the country. The most common tumour site was rectum in both the sexes and the most common histologic type was adenocarcinoma. The most common histological differentiation was moderate differentiation.&#x0D; Conclusion: The increased incidence in younger patients as compared to previous studies may be attributable to the lifestyle and dietary changes.

Desmoglein-3 overexpression in oral squamous cell carcinoma is associated with metastasis formation and early recurrence: An immunohistochemical study

The purpose of this study was to determine the expression patterns of specific desmosomal cadherins (desmogleins [DSG] 1/2/3) in oral squamous cell carcinoma (OSCC), and to examine possible associations with clinicopathological parameters and recurrence rates. Changes in desmosomal cadherin assembly may promote tumor metastasis formation.Patients with surgically treated OSCC with 36–60 months of follow-up (median 46 months) qualified for inclusion in this retrospective cohort study. Demographic, clinical and pathohistological data were collected. DSG-1/2/3 expression patterns were determined by an immunohistochemical approach on tissue microarrays. Descriptive and inferential statistics and survival analyses were computed (p ≤ 0.05).The study sample consisted of 88 patients (female: 38; male: 50; average age: 63.02 ± 17.5 years). DSG-3 overexpression was detected in 45 of 88 specimens. The expression rates for DSG-1 (28/88) and DSG-2 (14/88) were low and inconspicuous. DSG-3 overexpression was significantly associated with poor histologic differentiation (G3, p = 0.001), the presence of cervical node metastasis at primary diagnosis (N+ status, p = 0.001) and early recurrence (p = 0.001).Due to its possible relevance for lymph node metastasis formation and early OSCC recurrence, determination of DSG-3 expression in OSCC specimens may be a valuable tool for treatment planning and post-therapeutic risk assessment.

Dual-energy CT-based radiomics nomogram in predicting histological differentiation of head and neck squamous carcinoma: a multicenter study.

To develop and validate a dual-energy CT (DECT)-based radiomics nomogram from multicenter trials for predicting the histological differentiation of head and neck squamous cell carcinoma (HNSCC). A total of 178 patients (112 in the training and 66 in the validation cohorts) from eight institutions with histologically proven HNSCCs were included in this retrospective study. Radiomics-signature models were constructed from features extracted from virtual monoenergetic images (VMI) and iodine-based material decomposition images (IMDI), reconstructed from venous-phase DECT images. Clinical factors were also assessed to build a clinical model. Multivariate logistic regression analysis was used to develop a nomogram combining the radiomics signature models and clinical model for predicting poorly differentiated HNSCC and moderately well-differentiated HNSCC. The predictive performance of the clinical model, radiomics signature models, and nomogram was compared. The calibration degree of the nomogram was also assessed. The tumor location, VMI-signature, and IMDI-signature were associated with the degree of HNSCC differentiation, and areas under the ROC curves (AUCs) were 0.729, 0.890, and 0.833 in the training cohort and 0.627, 0.859, and 0.843 in the validation cohort, respectively. The nomogram incorporating tumor location and two radiomics-signature models yielded the best performance in training (AUC = 0.987) and validation (AUC = 0.968) cohorts with a good calibration degree. The nomogram that integrated the DECT-based radiomics-signature models and tumor location showed good performance in predicting histological differentiation degree of HNSCC, providing a novel combination for predicting HNSCC differentiation.

IMMUNOHISTOCHEMICAL FEATURES IN SOFT TISSUE SARCOMAS

Sarcomas are relatively rare, accounting for only 1% of all adult malignancies and 15% of childhood malignancies [2]. According to the World Health Organization (WHO), the group of soft tissue sarcomas includes more than 100 different histological subtypes [3]. According to the recommmendations of the WHO to improve the accuracy of diagnosis in soft tissue sarcoma, the traditional histopathological examination should be supplemented with immunohistochemical and molecular methods [1]. It was carried out immunohistochemical research of CD31 receptor of Vascular Endothelial Growth Factor (VEGF) in 129 patients with STS. The age range of patients is on average 14-77 years with a peak in the age of 50-59 years. The most common reason for initial visit to a medical institution was palpable tumor (100%). It was studied the following correlative interdependences: It was determined that histodifferentiation of tumour is in inverse correlation with expression CD31 receptor. Distinctions of expression level of CD31 are shown, depending on the degree of tumor differentiation, presence or absence of its spontaneous necrotization, limphoid infiltration of pathological nidus and amount of vessels in tumor tissue. That is as high the degree of histological differentiation of tumour as low the level of expression CD31 receptor (χ2=35,4; p&lt;0,001; р=-0,322). In FHTof ST is exposed inverse dependence between expression CD31 endotelial cells with spontaneous necrosis and lymphoid infiltration. As more the size and foci of spontaneous necrosis (χ2=67,1; p&lt;0,001; р=-0,473) and lymphoid infiltration (χ2=46,1; p&lt;0,001; р=-0,346), as low the level of expression CD31 receptor. It was found that the high level of espression CD31 receptor is in direct correlation with metastasis (χ2=18,6; р=0,42; p&lt;0,001) and recurrence (χ2=9,43; р=0,30; p&lt;0,01) of the process. Studied modern approaches to the diaqnostics and treatment of malignancies. One such approach is ”Oncology Control”, which means minimizing the risk of recurrence at the local and systemic level. Following treatment, follow-up should include history and physical examination accompanied by imaging (Ultrasound or MRI) every 3 to 6 month for 2 to 3 years, and then every 6 to 12 months thereafter to asses for recurrence. So in high positivity of CD31 receptor is exposed unfavourable prognosis in patients with STS. Summarizing before said we have come to the conclusion that immune-histo-chemical investigation of CD31 receptor of VEGF has important prognostical meaning in patients STS.

Genome-wide identification and expression analysis of the bZIP transcription factors, and functional analysis in response to drought and cold stresses in pear (Pyrus breschneideri)

BackgroundTranscription factors (TFs) are involved in many important biological processes, including cell stretching, histological differentiation, metabolic activity, seed storage, gene regulation, and response to abiotic and biotic stresses. Little is known about the functions, evolutionary history, and expression patterns of basic region-leucine zipper TF family genes in pear, despite the release of the genome of Chinese white pears (“Dangshansuli”).ResultsOverall, 92 bZIP genes were identified in the pear genome (Pyrus breschneideri). Of these, 83 were randomly distributed on all 17 chromosomes except chromosome 4, and the other 9 genes were located on loose scaffolding. The genes were divided into 14 subgroups. Whole-genome duplications, dispersed duplication, and purifying selection for whole-genome duplications are the main reasons for the expansion of the PbrbZIP gene family. The analysis of functional annotation enrichment indicated that most of the functions of PbrbZIP genes were enriched in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways involved in the abiotic stress response. Next, expression analysis and virus-induced gene silencing results indicated that PbrbZIP genes might play critical roles in response to drought and cold stresses, especially for the genes from subgroups A, C, G, I, and S.ConclusionsNinety-two PbrbZIP genes were identified from the pear genome and classified into 14 subgroups. PbrbZIP genes were mainly expanded from whole-genome duplications and dispersed duplications and retained by purifying selection. PbrbZIP genes were induced by cold and drought stresses and played important roles in drought and cold tolerance. These results provided useful information for further increasing the tolerance of pears to stresses and a foundation to study the cold and drought tolerance mechanism of PbrbZIP genes.

Lymph node micrometastasis of poorly differentiated node-negative gastric cancer risks a worse-than-expected survival outcome under standard management algorithm

BackgroundInvestigation of lymph node micrometastasis (mN) of gastric cancer has been focused on either T1 disease or T1-4N0 disease. Yet, it is unclear whether standard management algorithm toward poorly differentiated gastric cancer (PDGC) is more vulnerable to existence of mN, given its inherently biological aggressiveness, as compared with other histological types. Patients and methodsA surgical series (n = 3456) of gastric cancer categorized by histological differentiation was enrolled to analyze survival stratification. Of them, a cohort of T1-T4 N0 PDGC (n = 100) were subjected to cytokeratin immunohistochemistry, a surrogate of mN. ResultsCancer-specific survival by AJCC8 staging system could be nicely differentiated in both well-/moderately differentiated and signet ring cell types, while those between stage IA versus IB (p = 0.105), and stage IB versus IIA (p = 0.141) in PDGC could not. Thirteen (13%) out of 100 node-negative PDGC cases exhibited mN, with 5, 2, 5 and 1 cases occurring in T1, T2, T3, and T4 stage, respectively, without identifiable contributing factors. Prognostic performance of AJCC8 working upon PDGC became more discriminative by incorporating mN, as hazard ratio of stage IIIC referenced to stage IA increased from 43 to 78. ConclusionDefective discriminative survival of PDGC by standard staging algorithm prompted us to survey mN occurring in T1-T4N0 PDGC. The prognostic performance of AJCC8 working upon PDGC was enhanced by incorporating mN. As so, we recommend documentation of mN exclusively on node-negative PDGC that helps unveil stage migration phenomenon and switch to appropriate adjuvant therapy in need.

LKB1 expression and the prognosis of lung cancer: A meta-analysis.

Background:In the past few decades, many lines of evidence implicate the importance of liver kinase B1 (LKB1) as a tumor suppressor gene in the development and progression of solid tumours. However, the prognostic and clinicopathological value of LKB1 in patients with lung cancer are controversial. This article aimed to investigate the latest evidence on this question.Methods:A systematic literature searched in the PubMed, Web of Science, Embase, Cochrane library, Scopus until September 20, 2020. The association between overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), clinicopathological features and LKB1 were analysed by meta-analysis.Results:Eleven studies including 1507 patients were included in this meta-analysis. The pooled results revealed that low LKB1 expression was significantly associated with poor overall survival (OS) (HR = 1.67, 95% CI: 1.07–2.60, P = .024) in lung cancer. However, no association was found between LKB1 expression and DFS/PFS (HR = 1.29, 95% CI: 0.70–2.39, P = .410). Pooled results showed that low LKB1 expression was associated with histological differentiation (poor vs moderate or well, OR = 4.135, 95% CI:2.524–6.774, P < .001), nodal metastasis (absent vs present, OR = 0.503, 95% CI: 0.303–0.835, P = .008) and smoking (yes vs no, OR = 1.765, 95% CI: 1.120–2.782, P = .014).Conclusion:These results suggest that low expression of LKB1 can be considered as a unfavorable prognostic biomarker for human lung cancer, which should be further researched.

Cutaneous squamous cell carcinoma staging may influence management in users: A survey study.

PurposeThis study aims to determine whether there is consensus regarding staging and management of cutaneous squamous cell carcinoma (CSCC) across the various specialties that manage this disease.Materials and MethodsA survey regarding CSCC high‐risk features, staging, and management was created and emailed to cutaneous oncology experts including dermatology, head and neck surgery/surgical oncology, radiation oncology, and medical oncology.ResultsOne hundred fifty‐six (46%) of 357 invited physicians completed the survey. Depth of invasion (92%), perineural invasion (99%), histologic differentiation (85%), and patient immunosuppression (90%) achieved consensus (>80%) as high‐risk features of CSCC. Dermatologists were more likely to also choose clinical tumor diameter (79% vs. 54%) and histology (99% vs. 66%) as a high‐risk feature. Dermatologists were also more likely to utilize the Brigham and Women's Hospital (BWH) staging system alone or in conjunction with American Joint Committee on Cancer (AJCC) (71%), whereas other cancer specialists (OCS) tend to use only AJCC (71%). Respondents considered AJCC T3 and higher (90%) and BWH T2b and higher (100%) to be high risk and when they consider radiologic imaging, sentinel lymph node biopsy, post‐operative radiation therapy, and increased follow‐up. Notably, a large number of respondents do not use staging systems or tumor stage to determine treatment options beyond surgery in high‐risk CSCC.ConclusionThis survey study highlights areas of consensus and differences regarding the definition of high‐risk features of CSCC, staging approaches, and management patterns between dermatologists and OCS. High‐risk CSCC is defined as, but not limited to, BWH T2b and higher and AJCC T3 and higher, and these thresholds can be used to identify cases for which treatment beyond surgery may be considered. Dermatologists are more likely to utilize BWH staging, likely because BWH validation studies showing advantages over AJCC were published in dermatology journals and discussed at dermatology meetings. Additional data are necessary to develop a comprehensive risk‐based management approach for CSCC.

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP).

Background/AimsSeveral prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database.MethodsData from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated.ResultsBetween 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively.ConclusionsThe survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

CRISPR/Cas9-mediated knockout of SGLT1 inhibits proliferation and alters metabolism of gastric cancer cells

BackgroundThe roles played by sodium/glucose cotransporters 1 (SGLT1) that transport glucose in cells independent of extracellular glucose concentration in gastric cancer are unknown. MethodsThe expression of SGLT1 in 75 primary gastric cancer and paired adjacent normal tissue specimens was determined. Also, the underlying mechanism of the altered SGLT1 expression and its impact on the proliferation of the gastric cancer cells and their metabolism were investigated. ResultsSGLT1 expression was found to be positively associated with pT, pN, TNM staging, histological differentiation, and a worse overall survival. CRISPR/Cas9 mediated knockout of SGLT1 could inhibit proliferation of gastric cancer cells, promote their apoptosis, and could also alter the metabolism of gastric cancer cells. Mechanistically, the transcription activity of SGLT1 could be negatively regulated by p53. ConclusionsBesides identifying the important role of SGLT1 in gastric cancer, the underlying regulation mechanism in play was also elucidated. These make SGLT1 a promising new molecular target for the design of novel therapeutic modalities to control gastric cancer.

Micromorphological evaluation of Daphne mucronata Royle and Myrtus communis L. using scanning electron microscopic techniques.

The present study was undertaken to establish micromorphological standards of Daphne mucronata Royle and Myrtus communis (L.). Daphne mucronata Royle is a xerophytic perennial shrub while, Myrtus communis is an evergreen shrub or small tree. Micromorphological investigation is one of the cheapest methods. It will be helpful in the accurate identification of these plants from other species. Results of macroscopic evaluation showed various organoleptic features. Anatomy of the selected plant parts was carried out. It showed a typical dicot structure as it revealed the presence of epidermal cells, crystals, trichomes, cuticle, mesophyll tissues, xylem, phloem, paracytic, and dicytic stomata. Anatomical study facilitates the detection of adulteration with inferior commercial varieties, exhausted drugs, cheaper natural substances, and chemicals. Stomatal number, types, and size of stomata, and palisade ratio of Myrtus communis were observed. These observations will be helpful in the preparation of taxonomic key for the identification of selected species. Powder drug study [scanning electron microscopy (SEM)] showed characteristics histological differentiation. The methods cited here can be measured as characteristics to identify and validate these drugs.