Anaplastic (undifferentiated) carcinoma of pancreas, an uncommon variant: Diagnosed on endoscopic-guided fine needle aspiration

Anaplastic carcinoma of pancreas (ACP) are rare pancreatic neoplasms. They are well known to be associated with more aggressive tumor behavior and less favorable prognosis than usual pancreatic ductal adenocarcinoma. Endoscopic-guided fine needle aspiration (EUS-FNA) is now a widely accepted modality in diagnosis of pancreatic lesions. However, only a few reports are available describing cytological features of anaplastic carcinoma. Here, we report two cases of ACP diagnosed on EUS-FNA.

Role of cyclin D1 in glial tumors—A retrospective and observational study

Aim: High-grade glial tumors remain as one of the most lethal malignancies. Cyclin D1 is expressed in some human malignancies and is the potential target of intervention. The present study aims to determine the relationship of cyclin D1 expression with other clinicopathological parameters. Materials and Methods: A cross-sectional study was carried out in a tertiary care center. Biopsy proven 66 cases of glial tumor patients were included in the study. The patients with incomplete clinical details were excluded from the study. Immunohistochemistry using antibodies for IDH 1 and cyclin d1 was done in all the cases. Glial tumors were reclassified according to WHO 2016 classification. Data analysis was performed using SPSS 26.0 for the windows. Result: Among 66 patients, 49 (74.3%) were males and 17 (25.7%) were females. The age of the patients ranged from 20 years to 70 years. Overall, 6.02% were of grade I Glial tumors, 22.7% were of grade II Glial tumors, 19.6% patients were of grade III Glial tumors, and 51.6% patients were of grade IV Glial tumors. Of 66 samples tested cyclin D1 was positive in 25 (37.87%) as high expressers and 7 (10.60%) were low expressers. Our study showed a significant correlation between the expression of cyclin D1 with grade and IDH mutation status, No significant correlation of cyclin D1 was noted with age or sex of the patient. Conclusion: Cyclin D1 was associated with a higher grade of the glial tumor. It can be a potential marker both for prognosis and treatment of glial tumors.

Consideraciones clínicas y desenlaces quirúrgicos del cáncer asociado a implante mamario: una enfermedad emergente de interés

El cáncer de mama sigue siendo una de las principales prioridades en salud global y salud pública y permanece como la neoplasia maligna más frecuente y mortal en mujeres en el mundo. El linfoma anaplásico de células grandes asociado a implante mamario (LACG-AIM) consiste en un linfoma no-Hodgkin de tipo raro, del cual se desconoce mucho sobre su patogenia y fisiopatología, pero que se ve cada vez con mayor frecuencia, debido al aumento de procedimientos estéticos. A la fecha, existen limitaciones en cuanto al conocimiento sobre el comportamiento clínico y se manifiesta de muchas formas, con un tiempo de evolución variable, y desenlaces quirúrgicos inciertos a mediano y largo plazo. Con base en lo anterior, el objetivo de esta revisión consiste en resumir evidencia sobre las consideraciones clínicas y desenlaces quirúrgicos del cáncer asociado a implante mamario, que faciliten la identificación y abordaje de esta condición. Se realizó una búsqueda bibliográfica en los motores de búsqueda y bases de datos PubMed, ScienceDirect, Embase, EBSCO y MEDLINE. Dentro de las consideraciones clínicas y quirúrgicas, se debe tener en cuenta el tipo de implante utilizado (texturizado), el tiempo del antecedente del implante, la severidad de las manifestaciones y la estadificación, para poder determinar la oportunidad de intervención quirúrgica y terapia neoadyuvante e intentar garantizar la supervivencia y evitar recurrencia. Aquellos pacientes sometidos a capsulectomía completa acompañado de radioterapia tienen mejores desenlaces.

Breast cancer continues to be one of the main priorities in global health and public health, and remains the most frequent and deadly malignant neoplasm in women worldwide. Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of Non-Hodgkin's lymphoma, whose pathogenesis and pathophysiology are not well known, but which is seen with increasing frequency due to the increase in cosmetic procedures. To date, there are limitations in terms of knowledge about the clinical behavior of the disease, which can manifest itself in many forms, with a variable evolution time and uncertain surgical outcomes in the medium- and long-term. Based on the above, the aim of this review is to summarize evidence on the clinical considerations and surgical outcomes of breast implant-associated cancer to facilitate the identification and management of this condition. A bibliographic search was performed in the search engines and databases pubmed, sciencedirect, embase, ebsco and medline. Within the clinical and surgical considerations, the type of implant used (textured), the time of the implant history, the severity of the manifestations, and the staging, must be taken into account in order to determine the opportunity for surgical intervention and neoadjuvant therapy, and to try to guarantee survival and avoid recurrence. Patients who undergo complete capsulectomy with radiotherapy have better outcomes.

Early Onset Pulmonary Events and Management Strategies during the Treatment of ALK Positive NSCLC Patients with Brigatinib / 中国肺癌杂志

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase and its rearrangements occur in non-small cell lung cancer (NSCLC), resulting in signal dysregulation in kinase domain. As a new generation of potent ALK tyrosine kinase inhibitors (TKIs), Brigatinib was approved in China in March 2022 as a treatment for locally advanced or metastatic NSCLC patients with ALK rearrangement positive. Brigatinib significantly improved the survival, cranial efficacy and quality of life compared to Crizotinib in clinical trials. Brigatinib is generally well tolerated. Brigatinib has been one of the preferred treatments and an addition of options in ALK-rearranged NSCLC. Pulmonary toxicity is one of the adverse effects observed during the treatment of TKIs and deserves the intense attention of clinicians, despite of its low incidence rate. Pulmonary toxicity reported during the treatment of Brigatinib has shown distinct clinical presentations, such as early-onset (median time to onset, 2 days) and rapid tolerance and reversibility of symptoms. In view of this, the concept of early-onset pulmonary events (EOPEs) was proposed and established during the submission for regulatory review and approval. We focused on clinical characteristics, potential mechanism of etiology, and management strategies of EOPEs to provide clinicians evidence for better clinical decision support.
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Clinical analysis of seven cases of hemophagocytic lymphohistiocytosis secondary to cutaneous T-cell lymphoma / 中华皮肤科杂志

Objective:To investigate clinical and laboratory characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) associated with secondary cutaneous T-cell lymphoma (CTCL) .Methods:CTCL patients with clinically suspected sHLH were collected from Department of Hematology, Wuhan No.1 Hospital from January 2016 to October 2021, and were evaluated according to the HLH-2004 diagnostic criteria and HScore.Results:Seven CTCL patients were confirmedly diagnosed with sHLH, including 2 with primary cutaneous γδT-cell lymphoma (PC-GDTCL) , 3 with cutaneous extranodal natural killer/T-cell lymphoma (C-ENKTCL) , and 2 with primary cutaneous anaplastic large cell lymphoma (PC-ALCL) . All the 7 patients received chemotherapy, but 6 died finally, and the median overall survival duration was 26.5 days (range: 14 - 60 days) after the confirmed diagnosis of CTCL complicated by sHLH. HLH-related gene mutations, which were located in the PRF1 and LYST genes, were identified in 2 patients; lymphoma-related gene mutations were identified in the KRAS and KMT2D genes in 1 PC-GDTCL patient,and in the JAK3 and SAMHD1 genes in another PC-GDTCL patient.Conclusions:CTCL complicated by sHLH usually progresses rapidly, so early diagnosis and treatment are needed. Bone marrow biopsy and mutation screening of lymphoma- and HLH-related genes at initial diagnosis and during disease progression may facilitate early diagnosis.

Synergistic mechanisms of ferroptosis in anaplastic thyroid cancer induced by dihydroartemisinin and sorafenib / 中华内分泌代谢杂志

Objective:To investigate the synergistic effects and molecular mechanisms of dihydroartemisinin(DHA) and sorafenib(SOR) in inducing ferroptosis in anaplastic thyroid cancer(ATC) cells.Methods:CCK-8 and flow cytometry assays were performed to detect the effects of DHA and SOR on the proliferation and ferroptosis of ATC cells(CAL-62). Real-time fluorescence quantitative PCR and Western blotting assays were performed to detect the expressions of ferroptosis-related genes glutathione peroxidase 4(GPX4), solute carrier family 7 member 11 gene(SCL7A11), lipoxygenase-15(LOX-15), and p53. The levels of iron death intermediate metabolites including lactate dehydrogenase(LDH), glutathione(GSH), malondialdehyde(MDA), ferrous ion(Fe 2+ ), nitric oxide(NO), and reactive oxygen species(ROS)were measured by corresponding assay kits. The corresponding inhibition of DHA and SOR on ATC in vivo was analyzed in a tumor model in nude mice. Results:Compared with the control group, DHA, SOR, and DHA+ SOR treatment significantly inhibited cell proliferation and apoptosis in a dose-dependent manner( P<0.001), with increased LDH, Fe 2+, MDA, and ROS contents and reduced GSH activity( P<0.001), which were promoted by ferrous sulfate(FeSO 4)and reversed by ferroptosis inhibitor-1. Compared with the control group and the drug monotherapy group, 15-LOX-2 and p53 expressions were upregulated in DHA+ SOR group while GPX4 and SCL7A11 expressions were decreased( P<0.001), without significant difference in 15-LOX-1 protein content. In addition, NO level was significantly increased in DHA+ SOR group( P<0.001). DHA and SOR inhibited tumor growth of ATC in vivo. Conclusion:DHA and SOR synergistically induced ferroptosis via upregulating the expression of 15-LOX-2 gene and inhibiting NO synthesis in ATC cells.

Research status of combined gene mutations in anaplastic thyroid cancer / 中华内分泌代谢杂志

Anaplastic thyroid cancer (ATC) is the most malignant thyroid cancer with a low incidence but high mortality. ATC is highly aggressive, rapidly progressing, and has poor prognosis. Current treatment options is not efficacious, so there is an urgent need to investigate its pathogenesis to update the treatment and improve the survival rate. Previous studies have found that most ATC can develop from well-differentiated thyroid cancer, and BRAF and RAS mutations are the key driving factors of ATC. TP53, PI3K pathway, PTEN, TERT, SWI/SNF complex Subunit, NF2 and other mutations also play an important role in the occurrence of ATC. Recent studies have found that single gene mutation is often not sufficient to drive the occurrence of ATC, and ATC is usually developed from the accumulation of multiple mutations in well-differentiated thyroid cancer. Therefore, this paper reviews the role of common combined mutations in ATC, deepens the understanding of the pathogenesis, and provides a basis for finding effective therapeutic targets.

Explante de prótese mamária de silicone: reconstrução da mama pela técnica dos retalhos cruzados / Silicone breast prosthesis explant: breast reconstruction using the crossed flap technique

Introdução: Em 1963 Cronin e Gerow introduziram o uso do implante de silicone e seu uso aumentou exponencialmente. Contudo, complicações relacionadas aos implantes surgiram ao longo do tempo. O conjunto de situações adversas ao uso dos implantes de silicone, alimentado pelo crescimento das mídias sociais, culminou em um aumento da retirada definitiva do implante. Muitos casos de explante têm o pedículo inferior comprometido pela lesão dos vasos perfurantes e a técnica dos retalhos cruzados é uma alternativa para a reconstrução das mamas explantadas. Métodos: Foram realizados explantes de silicone com reconstrução imediata da mama sem o uso de um novo implante, motivados por indicação médica ou por desejo próprio do paciente. A técnica dos retalhos cruzados foi utilizada em todos os casos. Ela se vale do cruzamento de retalhos parenquimatosos de pedículo superior, um medial e outro lateral, conforme descrito por Sperli. Resultados: Foram operados 10 casos de 2004 a 2021. O tempo de uso das próteses variou de 3 a 19 anos e a principal motivação para o explante foi contratura capsular. Nenhum caso de necrose foi observado. Conclusões: A técnica dos retalhos cruzados é uma alternativa útil e segura para as cirurgias de reconstrução da mama após explante definitivo.

Introduction: In 1963 Cronin and Gerow introduced the use of the silicone implant and its use increased exponentially. However, complications related to implants emerged over time. The set of adverse situations to the use of silicone implants fueled by the growth of social media culminated in an increase in the permanent removal of the implant. Many cases of explants have the inferior pedicle compromised by injury to the perforating vessels, and the crossed flap technique is an alternative for the reconstruction of explanted breasts. Methods: Silicone explants were performed with immediate breast reconstruction without the use of a new implant, motivated by medical indication or the patients own desire. The crossed flap technique was used in all cases. It uses the crossing of parenchymal patches of the superior pedicle, one medial and one lateral, as described by Sperli. Results: 10 cases were operated from 2004 to 2021. The time of use of the prostheses ranged from 3 to 19 years and the main motivation for the explant was capsular contracture. No cases of necrosis were observed. Conclusions: The crossed flap technique is a useful and safe alternative for breast reconstruction surgeries after definitive explantation.

Extra-Axial supratentorial anaplastic ependymoma: Unusual location of an aggressive tumor, A case report

Introduction: Ependymomas are more common in the pediatric population, in whom they are commonly infratentorial. Extra axial location of a supratentorial ependymoma is extremely rare. Diagnosis: Radiologically these tumors are often misdiagnosed as meningioma or other extra axial lesions owing to their unusual location and lack of any pathognomonic features. Hence, histopathological examination becomes imperative for proper evaluation and an adequate diagnosis. Case: Herein we report a case of a supratentorial extra axial anaplastic ependymoma misdiagnosed as a metastatic tumor on radiological examination and mimicking meningioma intra operatively, located in the frontal and temporal region in a 20 year old man.

ALK-positive large B-cell lymphomas: A clinicopathologic study

Background and Aim: Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphomas (ALK+-LBCLs) are aggressive CD20-negative lymphomas, accounting for <1% of diffuse LBCLs. Being rare and with peculiar immunophenotypic characteristics, these can be easily misdiagnosed. We present 11 cases of ALK+-LBCLs diagnosed over a period of 11 years at a tertiary care hospital in South India to analyze the clinical, morphological, and immunophenotypic profile of these tumors. Subjects and Methods: ALK+-LBCL cases diagnosed from September 2009 to August 2020 were included. Clinical details were obtained from stored electronic records and summarized. Available hematoxylin and eosin (H and E) stained slides and immunohistochemistry slides were reviewed and observations tabulated. Results: Eleven patients (nine males and two females) were diagnosed with ALK+-LBCLs in the study period with seven presenting primarily with extranodal disease manifestations. Tumors in the lymph nodes showed diffuse architecture effacement and variable sinusoidal invasion. All tumors showed immunoblastic and plasmablastic-type large lymphoid cells with scattered anaplastic/multinucleate large cells, including rare Reed–Sternberg-like cells. Cytoplasmic granular ALK-1 staining, CD20 negativity, and immunohistochemical features of plasmablastic differentiation were noted in all. Of eight patients treated, only one achieved remission with multi-agent chemotherapy but relapsed after 6 months. Two patients died of disease and five others had progressive/persistent disease and were lost to follow-up. Conclusion: Although rare, these tumors should always be in the differential diagnoses of tumors with plasmablastic and immunoblastic morphology, especially in extranodal sites to avoid diagnostic delay/misdiagnosis.

Predictive role of neutropenia under crizotinib treatment in ALK?rearranged nonsmall cell lung cancer patients: A single?institution retrospective analysis

Background: Anaplastic lymphoma kinase (ALK)?rearranged nonsmall cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Tyrosine kinase inhibitor crizotinib, an anticancer drug acting as an ALK inhibitor, has shown remarkable response in ALK?positive NSCLC. The aim of our study is to explore the adverse events (AEs) of patients on crizotinib therapy and analyze the predictability of AEs for better survival or response on NSCLC patients. Methods: The medical records of our ALK?positive metastatic NSCLC patients who applied between years 2013 and 2018 had been reviewed retrospectively. ALK positivity of all patients had been detected by fluorescence in situ hybridization and no other driver mutations were present. Patient demographics, performance status, smoking history, previous treatments, metastatic sites, and AEs were recorded for further analyses. Results: Thirty?six ALK?positive metastatic NSCLC patients were included in the study. Median follow?up was 30.1 months. Median progression?free survival (PFS) for patients who developed hepatic, cardiac, or endocrine toxicities was similar when compared to patients who did not develop. Although there was a numeric median PFS difference between patients who did develop visual disorders (18.4 months) and did not develop visual disorders (15.5 month), this was not regarded as statistically significant. However, median PFS of the patients who developed neutropenia upon crizotinib treatment (31.9 months) was found to be more favorable than the patients with normal neutrophil counts (12.8 months) (P = 0.026). Conclusion: Neutropenia under crizotinib treatment was found to be associated with improved PFS suggesting that neutropenia might be an important determinant in treatment and survival strategies.

Primary leiomyosarcoma of the thyroid gland

Sarcoma is a rare tumor of the thyroid gland, primary thyroid leiomyosarcoma (LMS) being even rarer. We present a case of LMS of the thyroid in a middle-aged female. Histopathologic examination in conjunction with immunohistochemistry helped to clinch the diagnosis. Knowledge of this entity is important to distinguish it from anaplastic thyroid carcinoma (ATC) and other sarcomas arising in the thyroid and adjacent soft tissue. The prognosis of thyroid LMS is dismal with an extremely poor survival rate.

Case report of anaplastic lymphoma kinase positive histiocytosis in children / 中华实用儿科临床杂志

The clinical data of a child with anaplastic lymphoma kinase positive histiocytosis (ALK+ H) diagnosed in April 2020 by Kunming Children′s Hospital were retrospectively analyzed.The male child was 4 months and 29 days old and had multiple nodules throughout the body since 1 week after birth.Skin sarcoidosis examination showed non-Langerhans cell histiocytosis, and immunohistochemistry showed ALK (+ ), CD1a (-), and CD 163(+ ). Therefore, this patient was diagnosed as ALK+ H, which was very rare in clinical practice.Previously reported cases mainly showed soft tissue nodules or thrombocytopenia with anemia.In addition to multiple nodules throughout the body, this patient also had elevated platelets, neutropenia, and abnormal liver function, which was different from previous reports.Hence, this case could be used as a supplement to the disease database.

Clinical characteristics and prognosis analysis of patients with primary systemic anaplastic large cell lymphoma / 白血病·淋巴瘤

Objective:To explore the clinical charateristics and prognostic factors of patients with primary systemic anaplastic large cell lymphoma (ALCL).Methods:The clinicopathological data of 31 patients with newly treated primary systemic ALCL in Liaoning Cancer Hospital from January 2010 to December 2020 were retrospectively analyzed. Kaplan-Meier method was used to make survival analysis and log-rank test was performed. Multivariate analysis of factors influencing overall survival (OS) was performed by using Cox proportional hazards model.Results:Among 31 patients, there were 19 males and 12 females, with a median age of 47 years old, ranging from 16 to 74 years old. There were 18 (58.1%) patients with B symptoms, 16 (51.6%) patients with increased platelet count, 22 (71.0%) patients with Ann Arbor stage Ⅲ-Ⅳ. Until the end of follow-up, 22 cases survived and 9 cases died; the 5-year OS rate was 70.9%, and the median OS time was not reached. The 5-year OS rate of patients receiving CHOPE chemotherapy regimen was higher than that of patients receiving CHOP and other chemotherapy regimens, and the difference was statistically significant ( P = 0.049). There were statistically significant differences in the 5-year OS rates of patients with different platelet count, international prognostic index (IPI) score, chemotherapy regimens and with or without B symptoms (all P < 0.05). Multivariate analysis indicated that IPI score was an independent factor affecting OS ( HR = 2.194, 95% CI 1.078-4.465, P = 0.030). Conclusions:Most primary systemic ALCL patients are diagnosed at advanced stage and it is more common in males. Most patients have B symptoms and high platelet count. IPI score is an important prognostic factor, and CHOPE regimen may be a good choice of the first-line chemotherapy.

Effects of autophagy-mediated crizotinib resistance on cancer stem-like cell subsets in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma and its significance / 白血病·淋巴瘤

Objective:To investigate the effects of autophagy-mediated crizotinib resistance on cancer stem-like cell subsets in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALK + ALCL). Methods:The preliminary research of our group divided ALK + ALCL Karpas299 cell line into two subgroups: reporter unresponsive (RU) and reporter responsive (RR) cells through the implantation of Sox2 reporter genes, among which the RR cells had the characteristics of stem cells. Fluorescent labeled LC3 overexpressing RR and RU cells (RR-LC3 and RU-LC3) were constructed by lentiviral transfection technique, and the transfection efficiency was verified by using Western blotting and flow cytometry. RU-LC3 and RR-LC3 were treated with crizotinib at different concentrations (0, 250, 500, 1 000 nmol/L). The RED and GEN signals were detected by using double-signal flow cytometry to observe autophagy flux (RED represents the red signal B695 of the next generation of far-red fluorescent protein TagFP635 mKate; GEN represents the green signal from pH-sensitive GFP variant pHluorin B530), and the RED to GEV ratio represents autophagy flux. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect autophagy related genes ULK1, WIPI1 and LC3B mRNA expression levels in cells. The effects of different concentrations of crizotinib (250, 500, 1 000 nmol/L) combined with chloroquine (5, 10 μmol/L) on the cell survival were detected by using MTS assay. Results:RU-LC3 and RR-LC3 cells with overexpression of LC3 were successfully constructed. After induction of 250, 500 and 1 000 nmol/L crizotinib, the RED to GEN ratio in RU-LC3 cells was 1.135±0.017, 1.453±0.017 and 1.755±0.021, respectively; the RED to GEN ratio in RR-LC3 cells was 1.193±0.018, 2.116±0.013 and 3.307±0.189, respectively; the RED to GEN ratio in RU-LC3 cells and RR-LC3 cells showed a dose-dependent manner. The RED to GEN ratio in RR-LC3 cells was higher than that in RU-LC3 cells when treated with same concentrations of crizotinib, and the differences were statistically significant (all P < 0.01). The autophagy flux of RR-LC3 cells was larger than that of RU-LC3 cells. When treated without crizotinib, mRNA relative expression levels of ULK1, WIPI1 and LC3B in RR cells were higher than those in RU cells (1.69±0.05 vs.1.01±0.02, t = -1.62, P < 0.01; 1.24±0.04 vs. 1.03±0.05, t = -2.11, P < 0.01; 1.70±0.22 vs. 1.02±0.05, t = -1.74, P = 0.033). In the absence of chloroquine, the half-inhibitory concentration ( IC50) of crizotinib in RR cells was higher than that of RU cells (950 nmol/L vs. 709 nmol/L). After treated with chloroquine, IC50 of RU cells did not change, while IC50 of RR cells was decreased with the increase of chloroquine concentration. Conclusions:Compared with RU cells, autophagy reaction of cancer stem-like RR cells is more rapid and intense, which is considered to be one of the important reasons for their resistance to crizotinib.

Relationship between EGFR, ALK Gene Mutation and Imaging and Pathological Features in Invasive Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#At present, the research progress of targeted therapy for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations in lung adenocarcinoma is very rapid, which brings new hope for the treatment of advanced lung adenocarcinoma patients. However, the specific imaging and pathological features of EGFR and ALK gene mutations in adenocarcinoma are still controversial. This study will further explore the correlation between EGFR, ALK gene mutations and imaging and pathological features in invasive lung adenocarcinoma.@*METHODS@#A total of 525 patients with lung adenocarcinoma who underwent surgery in our center from January 2018 to December 2019 were included. According to the results of postoperative gene detection, the patients were divided into EGFR gene mutation group, ALK gene mutation group and wild group, and the EGFR gene mutation group was divided into exon 19 and exon 21 subtypes. The pathological features of the mutation group and wild group, such as histological subtype, lymph node metastasis, visceral pleural invasion (VPI) and imaging features such as tumor diameter, consolidation tumor ratio (CTR), lobulation sign, spiculation sign, pleural retraction sign, air bronchus sign and vacuole sign were analyzed by univariate analysis and multivariate Logistic regression analysis to explore whether the gene mutation group had specific manifestations.@*RESULTS@#EGFR gene mutation group was common in women (OR=2.041, P=0.001), with more pleural traction sign (OR=1.506, P=0.042), and had little correlation with lymph node metastasis and VPI (P>0.05). Among them, exon 21 subtype was more common in older (OR=1.022, P=0.036), women (OR=2.010, P=0.007), and was associated with larger tumor diameter (OR=1.360, P=0.039) and pleural traction sign (OR=1.754, P=0.029). Exon 19 subtype was common in women (OR=2.230, P=0.009), with a high proportion of solid components (OR=1.589, P=0.047) and more lobulation sign (OR=2.762, P=0.026). ALK gene mutations were likely to occur in younger patients (OR=2.950, P=0.045), with somking history (OR=1.070, P=0.002), and there were more micropapillary components (OR=4.184, P=0.019) and VPI (OR=2.986, P=0.034) in pathology.@*CONCLUSIONS@#The EGFR and ALK genes mutated adenocarcinomas have specific imaging and clinicopathological features, and the mutations in exon 19 or exon 21 subtype have different imaging features, which is of great significance in guiding the clinical diagnosis and treatment of pulmonary nodules.

The auxiliary diagnostic value of combined detection of serum midkine and thyroid stimulating hormone for differentiated thyroid cancer / 中国医师进修杂志

Objective:To investigate the auxiliary diagnostic value of serum midkine (MK) and thyroid stimulating hormone (TSH) for differentiated thyroid cancer (DTC).Methods:Seventy-one postoperative DTC patients (DTC group) treated with 131I were selected, and 143 patients with benign thyroid lesions (benign thyroid disease group) treated with surgery in Center Hospital of Xiaogan from March 2019 to December 2020 at the same period were also selected. Clinical data such as liver and kidney function indexes, positive rate of anti thyroglobulin antibodies (TGAb) and positive rate of thyroid peroxidase antibody (TPOAb) were collected before treatment, and their fasting blood samples were collected before treatment. Fully automated electrochemiluminescence immunoassay was used to measure free thyroxine (FT 4), free triiodothyronine (FT 3), TSH levels in patients′ serum. The serum MK levels were measured by enzyme-linked immunosorbent assay (ELISA). Binary Logistic regression model was used to screen for independent risk factors for the development of DTC. A receiver operating characteristic curve (ROC) was drawn to evaluate the efficacy of MK, TSH and MK combined with TSH, in aiding the diagnosis of DTC and its staging. Results:Serum TSH and MK levels in DTC group were higher than those in benign thyroid disease group: (3.55 ± 0.61) mU/L vs. (2.97 ± 0.46) mU/L, (394.25 ± 63.36) ng/L vs. (311.45 ± 42.66) ng/L, and the differences were statistically significant ( P<0.05). Elevated serum TSH and MK levels were independent risk factors for DTC. When MK combined with TSH was used to diagnose DTC, the area under the curve (AUC), sensitivity and specificity were higher than those of MK and TSH alone (0.925 vs. 0.859 and 0.783, 83.10% vs. 78.87% and 73.24%, 89.51% vs. 85.31% and 79.02%), and the differences were statistically significant ( P<0.05). Serum TSH and MK levels in stage Ⅲ and Ⅳ patients in DTC group were higher than those in stage Ⅰ and Ⅱ patients: (3.79 ± 0.65) mU/L vs. (3.42 ± 0.56) mU/L, (427.88 ± 52.73) ng/L vs. (311.45 ± 42.66) ng/L, and the differences were statistically significant ( P<0.05). The AUC, sensitivity and specificity of MK combined with TSH in the diagnosis of different stages of DTC were higher than those of MK and TSH alone (0.822 vs. 0.657 and 0.666, 73.90% vs. 56.52% and 56.52%, 83.33% vs. 77.08% and 79.17%), and the differences were statistically significant ( P<0.05). Conclusions:Serum TSH and MK levels are independent risk factors for the occurrence of DTC in patients, and the combination of them has certain auxiliary diagnostic value for the identification and staging of DTC.

Comprehensive Treatment of Anaplastic Thyroid Cancer / 肿瘤防治研究

Anaplastic thyroid cancer (ATC) is a rare malignancy, accounting for 1%-2% of all thyroid cancers, however, ATC accounts for the majority of deaths from thyroid cancer. Currently, the main comprehensive treatments are surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy. Based on the latest American Thyroid Association guidelines and the related literatures, we summarize the most reasonable and effective therapeutic strategies to improve the survival rate of patients with ATC as well as the quality of life.

Pharmacoeconomic evaluation of ensatinib in the first-line treatment of anaplastic lymphoma kinase-positive advanced non-small cell lung cancer / 中国药房

OBJECTIVE To evaluate the econo mical efficiency of ensatinib i n the first-line treatment of anaplastic lymphoma kinase（ALK）positive-advanced non-small cell lung cancer （NSCLC），so as to provide reference for China ’s medical insurance decision-making and rational drug use in clinic. METHODS A three-state partitioned survival model was constructed from the perspective of China ’s health system ，based on the data of the international multi-center phase Ⅲ clinical trial （eXalt3 trail），with simulation time limit of 10 years，cycle period of 30 days. The economical efficiency of ensatinib was compared with that of crizotinib（standard treatment ）in the first-line treatment of ALK positive-advanced NSCLC. The incremental cost-effectiveness ratio （ICER） was calculated with quality-adjusted life years （QALYs） as utility index. The stability of basic analysis results was validated through uncertainty analysis. RESULTS The basic analysis results showed that compared with crizotinib group ， incremental cost per capita of ensatinib group was －343 370.36 yuan，incremental utility per capita was 0.76 QALYs，ICER was －454 292.25 yuan/QALY，which was far lower than the willingness-to-pay （WTP）threshold of 1 time of China ’s per capita gross domestic product （GDP，80 976 yuan）in 2021. The results of univariate sensitivity analysis showed that progression-free survival （PFS）status utility ，progression of disease （PD）status utility and subsequent treatment cost of crizotinib had a greater impact on ICER，but these parameters could not cause the reversal of basic analysis results. Probabilistic sensitivity analysis showed that with 1 time of China ’s per capita GDP in 2021 as the WTP threshold ，the probability of ensatinib group ’s treatment possessed economical efficiency was 100％. In the situational analysis ，ICER obtained by changing the ensatinib group ’s follow-up treatment regimen was －217 671.43 yuan/QALY，which was far below WTP threshold. CONCLUSIONS For Chinese patients with ALK positive-advanced NSCLC ，compared with commonly used the first-line treatment （crizotinib），ensartinib is economical and absolutely dominant.