Purpose: The aim of our study was to investigate the value of baseline and preoperative neutrophil-to-lymphocyte ratio (NLR) in predicting the pathological response and disease-free survival (DFS) of neoadjuvant chemotherapy alone or combined with programmed cell death-1 (PD-1) checkpoint inhibitors in patients with resectable non‒small cell lung cancer (NSCLC). Materials and Methods: Resectable NSCLC patients who underwent neoadjuvant chemotherapy alone or combined with PD-1 checkpoint inhibitors between January 2018 and January 2020 were included. Peripheral venous blood samples of the patients were collected within 3 days prior to the first neoadjuvant treatment and within 3 days prior to surgery. Results: A total of 79 patients in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group and 89 patients in neoadjuvant chemotherapy alone group were included. Thirty-five point four percent of the patients achieved pathological complete response (pCR) in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group, whereas only 9.0% reached pCR in the group of neoadjuvant chemotherapy. High NLR level were correlated with poor pathological response and DFS in neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors group. Multivariate analysis revealed that baseline NLR could independently predict pathological response and DFS in the neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group. Conclusion High NLR level were correlated with poor pathological response and shorter DFS in patients with NSCLC undergoing neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors. Meanwhile, baseline NLR could independently predict response to pathological response and DFS, revealing its potential as a screening tool in NSCLC patients who received neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Objective:To investigate the clinicopathological characteristics, diagnosis, differential diagnosis and prognostic factors of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC).Methods:Sixteen cases of SDSC diagnosed in the Department of Pathology, Beijing Tongren Hospital from January 2016 to September 2020 were enrolled. Ninety-nine cases of small round cell malignant tumors of the head and neck were selected as the control, including poorly-differentiated squamous cell carcinoma ( n=10), poorly-differentiated adenocarcinoma ( n=5), undifferentiated carcinoma (SNUC, n=4), NUT carcinoma ( n=5), neuroendocrine carcinoma ( n=10), and other non-epithelial tumors [olfactory neuroblastoma ( n=10), rhabdomyosarcoma ( n=10), NK/T-cell lymphoma ( n=10), malignant melanoma ( n=10), Ewing′s sarcoma/primitive neuroectodermal tumor (EWS/PNET, n=5)] and non-keratinizing undifferentiated nasopharyngeal carcinoma ( n=20). The clinical and pathologic characteristics of SDSC, and immunohistochemical (IHC) expression of broad-spectrum CKpan, CK7, CK8/18, CK5/6, p63, p40, p16, INI1, NUT and neuroendocrine markers (Syn, CgA, CD56) were evaluated. In situ hybridization (ISH) was used to detect EBER and fluorescence in situ hybridization (FISH) to detect INI1 gene deletion. Results:The 16 cases of SDSC accounted for 1.3% (16/1 218) of all malignant sinonasal tumors in the author′s unit during this time period, and 2.4% (16/657) of all malignant epithelial tumors. Microscopically, there was no clear squamous and adenomatous differentiation, but "rhabdoid-like" cells, are often seen. All SDSC cases were positive for CKpan and CK8/18, negative for INI1; Epstein-Barr virus was not detected by ISH; and INI1 gene deletion was observed in all 11 SDSC patients with FISH. Twelve cases were followed up for 3-47 months. One died of tumor-related diseases half a year after diagnosis, and the remaining patients were alive with tumor, the longest survival time was 47 months.Conclusion:SDSC should be differentiated from a variety of poorly-differentiated tumors in the sinonasal area. Histologically, SDSC has no clear differentiation, but the tumor cells are characteristically basal-like or rhabdoid-like, with non-specific vacuoles, translucent or vacuolar nuclei, prominent nucleoli and necrotic foci. They are negative for INI1 IHC staining, and FISH demonstrates INI1 gene deletion. The clinical prognosis is still unclear, further studies on its biologic behavior and treatment methods are warranted.

Lung cancer is the most common malignant tumor in the world. In order to improve the survival rate of patients with advanced lung cancer, more effective treatment methods are needed,in which immunotherapy has a broad therapeutic prospect. In recent years, immune-checkpoint inhibitors have received extensive attention in the treatment of lung cancer. Significant progress has been made in the development of a variety of first-line and second-line treatments, and significant advances have been made in the treatment of advanced lung cancer. With the successful application of immune-checkpoint inhibitors, neoadjuvant therapy has attracted extensive attention. In addition, the successful application of combined therapies such as immune combined immunization, immune combined tyrosine kinase inhibitor (TKI) and immune combined chemotherapy improved the survival rate of patients to some extent. However, pseudo progression and drug resistance has become a non-negligible problem in the immunotherapy of non-small cell lung cancer, which is worthy of further study. Although immune-checkpoint inhibitors have once again brought attention to tumor immunotherapy, their side effects are also worthy of attention. The recent advances in the application of immune-checkpoint inhibitors in lung cancer were summarized in order to provide a theoretical basis for its clinical application.

Currently, postoperative adjuvant chemotherapy is recommended for patients with stageⅡ-ⅢA non-small cell lung cancer (NSCLC). However, the toxicity of chemotherapy should not be neglected, despite the survival benefits achieved. There is an urgent need for new, effective, individualized treatment regimens with low toxicity. EGFR-TKI is widely used for the treatment of advanced NSCLC because of its high efficiency and low toxicity. To explore more effective treatment methodologies, researchers at home and abroad have made many attempts to extend targeted therapy to the field of postoperative adjuvant therapy. This article reviews the retrospective and prospective clinical studies that have been conducted, analyzes the preponderant population of postoperative adju-vant targeted therapy, and seeks evidence-based medical evidence to guide clinical practice, so that patients with NSCLC can benefit from targeted therapies and improved postoperative survival rates.

Objective To investigate the regeneration and differentiation of HOCs in the 2-AAF/PHx rat models. To explore the expression of Cyr61and its mechanism in differentiation of HOCs in vitro. Methods In 2-AAF/PHx rats model,induction and expansion of HOCs were detected by immunochemistry and HE staining. West-ern blot was used for observing the expression of Cyr61. Furthermore,the expression of Cyr61 andβ-catenin were detected by Western blot in differentiation of WB-F344 cells in vitro. Results Cyr61 protein level increased as a re-sult of HOCs in rats livers after 2-AAF/PHx. In addition,the expression of Cyr61 and β-catenin significantly in-creased during WB-F344 cells differentiation in vitro. Conclusions Cyr61 might play an important role as a signal-ing mediator in HOCs response and closely correlate with Cyr61 andβ-catenin in proliferation and differentiation of HOCs.

Objective To retrospectively analyze the relationship between progression free survival (PFS) and overall survival (OS) in patients with non small cell lung cancer (NSCLC), and to detect the influence of plasma fibrinogen and D-dimer levels before treatment in the prognosis of advanced stage (stageⅢB-Ⅳ) of NSCLC. Methods The study comprised 134 NSCLC patients with clear pathological diagnosis. All patients were grouped by plasma fibrinogen and D-dimer levels before treatment. We set the normal values of fibrinogen as≤4 g/L and D-dimer as≤500μg/L(FEU). Patients with normal levels of fibrinogen and D-dimer were grouped into low risk group, patients with elevated fibrinogen or D-dimer were grouped into median risk group, and patients with both elevated values were grouped into high risk group. Chi-square test and one way ANOVA analysis were used to analyze the clinicopathologic features of different groups. The OS and PFS in different groups were analyzed by Kaplan-Meier analysis. Univariate analysis of PFS and OS were conducted. Then multivariate analysis was conducted with the Cox regression model in three groups. Results The clinicopathologic features showed no differences between different groups. There were significant differences in OS and PFS between high risk group and other groups. In the survival curves, the high risk group showed poor prognosis. The result of multivariate analysis showed that clinical stage (OS:RR=1.846, 95%CI 1.150-2.964,P=0.011; PFS:RR=1.762, 95%CI 1.190-2.609, P=0.005) and grouped by fibrinogen and D-dimer (OS:RR=1.415,95%CI 1.050-1.908,P=0.023;PFS:RR=1.373,95%CI 1.070-1.761,P=0.013) were prognostic factors for patients with NSCLC. Conclusion The plasma fibrinogen and D-dimer levels before treatment are closely related with the prognosis of NSCLC patients. And a high plasma fibrinogen and D-dimer levels before treatment are associated with poor prognosis in advanced stage of NSCLC patients.

OBJECTIVETo study the clinicopathologic characteristics of IgG4-related sialodacryoadenitis and chronic rhinosinusitis (CRS).

METHODSA total of 13 patients (patient group) were evaluated clinically and biopsy specimens from the lacrimal/salivary glands (n=12) and nasal mucosa (n=8) were reviewed and immunohistochemistry was performed to assess IgG-and IgG4-positive cells. Similarly, nine patients with IgG4-related sialodacryoadenitis without CRS and 10 patients with common CRS were included as controls.

RESULTSThere were 8 male patients and 5 female patients. The age of patients ranged from 32 to 71 years (mean 50.2 years). The patient group had higher serum IgG4 concentration than that of the control group (P<0.05). Lymphoplasmacytic infiltration, lymphoid follicle formation and sclerosis were prominent in lacrimal/salivary glands in both groups; however the magnitude of IgG4-positive plasmacytic infiltration in the patient group was significantly higher than that of the control group (P<0.05). Similarly, evaluation of nasal mucosa revealed greater lymphocytic and plasmacytic infiltration, and lymphoid follicle formation, together with significantly higher amount of IgG4-positive plasma cell infiltration in the patient group compared to the common CRS group (P<0.05).

CONCLUSIONSIgG4-related disease (IgG4-RD) simultaneously involving lacrimal/salivary glands and nasal cavity/paranasal sinuses is rare and characterized by a combination of IgG4-positive plasma cell infiltration involving lacrimal/salivary glands and nasal mucosa along with an increased serum level of IgG4. As a systemic disease, early and accurate diagnosis is therefore of great importance, and unnecessary surgery should be avoided.

Adult ; Aged ; Chronic Disease ; Female ; Humans ; Immunoglobulin G ; blood ; Immunohistochemistry ; Lacrimal Apparatus ; pathology ; Male ; Middle Aged ; Nasal Mucosa ; pathology ; Paranasal Sinuses ; pathology ; Rhinitis ; diagnosis ; immunology ; Salivary Glands ; pathology ; Sialadenitis ; diagnosis ; immunology ; Sinusitis ; diagnosis ; immunology

OBJECTIVETo investigate the clinical and pathologic features of middle ear adenoma (MEA).

METHODSEight cases of MEA were collected from Beijing Tongren Hospital, Capital Medical University between 2004 and 2014, and immunohistochemical staining was performed.

RESULTSThe patients included five women and three men (mean age, 37.5 years; median 37 years; range, 21-51 years). All patients had unilateral lesions. Five MEA occurred on the left side, and three on the right. In seven patients the MEA was primary, and they presented with hearing loss (6 cases), tinnitus (5 cases), sense of ear blockage (3 cases), otalgia (1 case) and facial nerve paralysis (1 case). The remaining patient had recurrent MEA, and presented with otorrhea, aural fullness and tinnitus. Histologically, the tumor cells were arranged in a variety of patterns, including solid sheets, nests, glands, ribbons or trabeculae. Glandular structures were prominent in one case only. Immunohistochemically, the tumor cells were diffusely positive for keratin (8/8) and vimentin (8/8), and focally positive for CK 7(8/8) and CK5/6(8/8). CK7 and CK5/6 were predominantly positive in tumor cells with glandular growth pattern; CK7 was positive in the luminal cells while CK5/6 was positive in the abluminal cells. Both were also expressed focally in scattered tumor cells with non-glandular pattern. The tumor cells were also diffusely positive for synaptophysin(8/8), diffusely but weakly positive for NSE (5/8), and were diffusely or focally positive for chromogranin A (4/8). Both S-100 protein and calponin were negative in all cases. The proliferation rate was low, about 1%-2%. Six cases were followed up for one year and three months to ten years and six months, with an average follow-up period of four years and two months. Two patients developed recurrence, but there were no regional or distant metastases.

CONCLUSIONSDiagnosis of MEA requires pathologic confirmation since the clinical symptoms are non-specific. MEA can show a variety of histologic patterns, and should be distinguished from other space-occupying lesions at this site. Immunohistochemical staining has greatly contributed to the diagnosis and differential diagnosis of MEA. The prognosis of this tumor is good. Patients with MEA require long-term follow-up for recurrences.

Adenoma ; pathology ; Adult ; Beijing ; Diagnosis, Differential ; Ear Neoplasms ; pathology ; Ear, Middle ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Young Adult

OBJECTIVETo investigate the relationship between ALDH1A1 expression and lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC).

METHODSOne hundred and fifty-three paraffin-embedded specimens of PTC treated in the Beijing Tongren Hospital of Capital Medical University were selected from January 2006 to December 2013. The expression of ALDH1A1 was detected in both tumor tissues and adjacent non-tumor tissues by immunohistochemistry and several clinicopathological parameters (size, bilaterality, multifocality, tumor border and extrathyroidal extensions) were assessed by HE staining. The correlation of ALDH1A1 expression with LNM was analyzed.

RESULTSIn 153 cases of PTC, there were 82 cases with LNM, 126 cases with high ALDH1A1 expression in tumor tissues, and 112 cases with high ALDH1A1 expression in adjacent non-tumor tissues. On univariate analysis, patient age < 45 years, tumor size of 10 mm or more, invasive tumor border, and high ALDH1A1 expression in tumor tissues predicted LNM in PTC (P < 0.05), whereas gender, bilaterality, multifocality, extra-thyroidal extensions and high ALDH1A1 expression in adjacent non-tumor border did not (P > 0.05). On multivariate analysis, invasive tumor border, high ALDH1A1 expression in tumor tissues were found to be independent predictive factors for LNM in PTC (P < 0.05). After a follow-up of 42 months (median time), four patients developed locoregional recurrences, but no distance recurrence or disease related death were seen in 82 patients of follow up. The estimated 5-year locoregional recurrence was 4.88%. Of these four logcoregional recurrences, three involved lymph nodes and one involved the remaining thyroid. The ALDH1A1 expression in tumor tissues was high in all of recurrence cases.

CONCLUSIONHigh ALDH1A1 expression in tumor tissues is correlated with lymph node metastasis in PTC and may be used as an independent predictive factor of LNM, and may improve treatment and follow-up strategies for PTC.

Aldehyde Dehydrogenase ; metabolism ; Carcinoma ; metabolism ; pathology ; Carcinoma, Papillary ; Humans ; Immunohistochemistry ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Risk Factors ; Thyroid Neoplasms ; metabolism ; pathology