Novel Association of RAD54L Mutation with Müllerian Clear Cell Carcinoma of the Male Urethra: New Insights Regarding the Molecular Mechanisms of a Rare Tumour.

INTRODUCTION: Müllerian clear cell carcinoma of the male urethra is similar to that of the female genital tract in terms of morphology and immunohistochemical expression but is rarely observed in clinical practice. CASE PRESENTATION: Here, we report the case of a 65-year-old man diagnosed with Müllerian clear cell carcinoma who harboured a mutation in RAD54L. This patient was diagnosed by electrocautery and ultimately underwent prostatectomy. After a six-month follow-up period, no signs of recurrence or additional malignancy were found. Based on our analysis of the available literature, it appears that Müllerian clear cell carcinoma with RAD54L mutation has not been reported until now. CONCLUSION: This case enhances our knowledge of the molecular biology of Müllerian clear cell carcinoma of the male urethra, which will help clinicians select optimal treatment options for this rare cancer in patients with specific driver mutations.

Combination of high-frequency electrocautery therapy and ALA-PDT in hyperkeratotic vulvar lichen sclerosus: Series of seven cases.

SIGNIFICANCE: ALA-PDT effectively treats Vulvar lichen sclerosus et atrophicus (VLSA), but it requires multiple repetitions for satisfactory results. To enhance efficacy, we employed a combination of high-frequency electrocautery therapy and ALA-PDT in treating seven VLSA patients. APPROACH: Lesions and leukoplakia in the seven women with VLSA were removed using a high-frequency generator. PDT was administered after wound healing, and it was repeated six times. Follow-up assessments were carried out at 1, 3, and 6 months to evaluate the severity of pruritus and investigate lesion repigmentation. RESULTS: Following the combined therapy, the disappearance of pruritus was observed in all patients, and normal color and thickness were restored to their skin. Two patients reported mild pruritus with a score of 2 one month after treatment, which persisted until the 6-month follow-up, while the remaining patients remained free from pruritus. No recurrence of skin lesions was observed in any of the patients. CONCLUSIONS: The combined therapy for the treatment of VLSA is found to be convenient, effective, and easily promotable.

Magnetic resonance imaging findings of pulmonary sclerosing pneumocytoma: a case report and literature review.

Background: Pulmonary sclerosing pneumocytoma (PSP) is a rare lung tumor that is mostly isolated and commonly reported among middle-aged East Asian women. Recently, Immunohistochemistry (IHC) analysis has suggested that PSP is of primitive epithelial origin, most likely derived from type II alveolar air cells. Patients with PSP are generally asymptomatic and usually detected for other unrelated reasons during routine imaging. Several studies have already investigated the computed tomography (CT) features of PSP and their correlation with pathology. Magnetic resonance imaging (MRI) is a radiation-free imaging technique with important diagnostic value for specific pulmonary nodules. However, very few case reports or studies focus on the MRI findings of PSP. Case report: We reported a case of an asymptomatic 56-year-old female with a solitary, well-defined soft-tissue mass in the lower lobe of the left lung. The mass showed iso-to-high signal intensity (SI) than muscle on T1-weighted image (T1WI) and T2-weighted image (T2WI) and a much higher SI on fat-suppressed T2WI, diffusion-weighted image, and apparent diffusion coefficient image. Contrast-enhanced fat-suppressed T1WI revealed noticeable inhomogeneous progressive enhancement throughout the mass. The mass revealed early enhancement without a significant peak, followed by a plateau pattern on dynamic contrast-enhanced MRI images. The patient underwent left basal segmentectomy via thoracoscopic surgery. Histopathology and IHC results of the surgical specimen confirmed that it was a PSP. We concluded that the MRI findings of PSP might adequately reflect the different components within the tumor and aid clinicians in preoperative diagnosis and assessment. To the best of our knowledge, this is the most comprehensive case report on the MRI findings of PSP. Conclusion: The MRI findings of PSP correspond to its histopathological features. Here, we present a case of PSP with the most comprehensive MRI findings, emphasizing the importance of multiple-sequence MRI in diagnosing PSP.

Neoadjuvant docetaxel, oxaliplatin plus capecitabine versus oxaliplatin plus capecitabine for patients with locally advanced gastric adenocarcinoma: long-term results of a phase III randomized controlled trial.

BACKGROUND: Neoadjuvant chemotherapy with docetaxel, oxaliplatin, and capecitabine (DOX regimen) is rarely used in Eastern countries and its efficacy and safety in advanced gastric cancer have not been reported. In this open-label, randomized, controlled trial, the authors aimed to assess the clinical efficacy of neoadjuvant chemotherapy using the DOX and oxaliplatin plus capecitabine (XELOX) regimens, in comparison to surgery alone. MATERIALS AND METHODS: Three hundred patients younger than 60 years with potentially resectable advanced gastric cancer (cT3-4, Nany, M0) were enrolled in this randomized controlled clinical trial between November 2014 and June 2018. The primary endpoint of the study was the pathological complete response (pCR) rate. Secondary endpoints included 3-year overall survival (OS), 3-year disease-free survival. RESULTS: In total, 280 patients (93 in the DOX group, 92 in the XELOX group, and 95 in the surgery group) were included in the per-protocol analysis. The DOX group demonstrated a significantly higher pCR rate compared to the XELOX group (16.1 vs. 4.3%, P =0.008). For patients with intestinal type, the DOX group exhibited significantly higher rates of both pCR and major pathological response compared to the XELOX group ( P =0.007, P <0.001). The 3-year OS rates of the DOX group, the XELOX group and the surgery group were 56.9, 44.6, and 34.7%, respectively. The 3-year disease-free survival rates were 45.2, 40.2, and 28.4%, respectively. The neoadjuvant DOX regimen demonstrated a significant improvement in the 3-year OS of patients compared to the neoadjuvant XELOX regimen ( P =0.037). CONCLUSION: The neoadjuvant DOX regimen has shown the potential to increase the pCR rate and improve the prognosis of patients with advanced gastric cancer who are under 60 years old.

Multi-center study on predicting breast cancer lymph node status from core needle biopsy specimens using multi-modal and multi-instance deep learning.

The objective of our study is to develop a deep learning model based on clinicopathological data and digital pathological image of core needle biopsy specimens for predicting breast cancer lymph node metastasis. We collected 3701 patients from the Fourth Hospital of Hebei Medical University and 190 patients from four medical centers in Hebei Province. Integrating clinicopathological data and image features build multi-modal and multi-instance (MMMI) deep learning model to obtain the final prediction. For predicting with or without lymph node metastasis, the AUC was 0.770, 0.709, 0.809 based on the clinicopathological features, WSI and MMMI, respectively. For predicting four classification of lymph node status (no metastasis, isolated tumor cells (ITCs), micrometastasis, and macrometastasis), the prediction based on clinicopathological features, WSI and MMMI were compared. The AUC for no metastasis was 0.770, 0.709, 0.809, respectively; ITCs were 0.619, 0.531, 0.634, respectively; micrometastasis were 0.636, 0.617, 0.691, respectively; and macrometastasis were 0.748, 0.691, 0.758, respectively. The MMMI model achieved the highest prediction accuracy. For prediction of different molecular types of breast cancer, MMMI demonstrated a better prediction accuracy for any type of lymph node status, especially in the molecular type of triple negative breast cancer (TNBC). In the external validation sets, MMMI also showed better prediction accuracy in the four classification, with AUC of 0.725, 0.757, 0.525, and 0.708, respectively. Finally, we developed a breast cancer lymph node metastasis prediction model based on a MMMI model. Through all cases tests, the results showed that the overall prediction ability was high.

Clinicopathological characteristics of rectal multiple neuroendocrine neoplasms and literature review.

BACKGROUND: There are only a few epidemiological reports available for reference. The clinicopathological features are not clear, so there is no consensus on treating rectal multiple neuroendocrine neoplasms. This study aims to summarize the clinicopathological characteristics and preliminarily discuss the clinical diagnosis and treatment of rectal multiple neuroendocrine neoplasms. METHODS: This study retrospectively analyzed rectal neuroendocrine neoplasm patients diagnosed and treated at the Fourth Hospital of Hebei Medical University from February 2007 to May 2021. The clinicopathological characteristics of rectal multiple neuroendocrine neoplasms were summarized and analyzed in combination with 14 studies on rectal multiple neuroendocrine neoplasms. RESULTS: The incidence of RM-NENs accounted for 3.8% of all R-NENs in this study. The number of tumors varied to some extent, the size of tumors was basically no more than 10 mm, and there were more G1 grade tumors. In the analysis of 46 cases with known lymph node metastasis, the difference in lymph node metastasis rate between the number of tumors < 8 and ≥ 8 was statistically significant (p = 0.002). CONCLUSIONS: The incidence of rectal multiple neuroendocrine neoplasms accounted for 3.8% of all rectal neuroendocrine neoplasms. For rectal multiple neuroendocrine neoplasms, the lymph node metastasis rate was higher when the number of tumors was ≥ 8. The influence of the number of tumors on lymph node metastasis should be considered in the selection of treatment.

A clinical diagnostic test on the detection of sentinel lymph node metastasis in breast neoplasms using a 1-step RT-PCR.

Background: Currently, assessment of sentinel lymph node (SLN) requires cytology, hematoxylin-eosin (HE), and immunohistochemistry (IHC). However, routine pathological slides still suffer from certain sampling errors and have time limitations. This study sought to investigate the sensitivity and specificity of SLN detection by reverse transcription-polymerase chain reaction (RT-PCR), which quantifies the expression of mammaglobin and cytokeratin-19 genes to determine SLN status. Methods: The RT-PCR detection of cycles threshold (CT) values has a direct relationship with the lymph node metastasis. This study prospectively collected 256 sentinel lymph nodes from 150 patients diagnosed with breast cancer between August and November 2017. In the detection of metastases in lymph nodes, molecular markers can be verified at the cell-level and tissue-level of tumor cells. In this study, IHC results were used as the gold standard for judging sentinel lymph node status. Results: (I) According to the established cell models, as the lymph nodes in tumor cells increase, RT-PCR CT values decrease. (II) 83 lymph nodes were first collected, and the interpretation criteria for the molecular detection results were determined based on the IHC results. (III) The statistical analysis showed that the sensitivity of the RT-PCR was 80.49% and the specificity was 91.55%. The positive predictive and negative predictive values were 64.71% and 96.06%, respectively. There was no significant difference between RT-PCR detection and IHC detection (P=0.076). Statistical chi-square analysis also showed that the difference between intraoperative freezing and immunohistochemistry was statistically significant (P=0.000). There was a statistically significant difference between intraoperative freezing and RT-PCR detection (P=0.000). RT-PCR detection is more sensitive than intraoperative frozen detection, and is closer to the results of immunohistochemistry. Conclusions: RT-PCR had objective and rapid output advantages, and was proven to be true and reliable. RT-PCR detection can not only rapidly assess sentinel lymph node status in breast cancer patients during surgery, but its accuracy is also close to that of IHC. Correctly determine whether to perform axillary lymph node dissection and improve the survival rate of patients.

Adjuvant chemotherapy can benefit the survival of stage I lung adenocarcinoma patients with tumour spread through air spaces after resection: Propensity-score matched analysis.

Background: It is still unclear whether stage I lung adenocarcinoma patients with tumour spread through air spaces (STAS) can benefit from postoperative adjuvant chemotherapy (ACT) after lobectomy. This study investigated the effect of ACT on the postoperative survival of patients with stage I (STAS+) lung adenocarcinoma. Methods: We retrospectively analysed the clinical data of stage I (STAS+) invasive lung adenocarcinoma patients who underwent lobectomy in the Department of Thoracic Surgery of our hospital from January 1, 2013 to January 1, 2016. Propensity score matching (PSM) was performed to group patients to investigate whether ACT could lead to better prognosis of patients. Results: A total of 593 patients with stage I (STAS+) lung adenocarcinoma were enrolled. The study after PSM included 406 patients. Kaplan-Meier survival analysis showed the experimental group had a better 3-year recurrence-free survival (RFS) rate (p = 0.037) and the 5-year RFS rate (p = 0.022) than the control group. It also had higher 5-year overall survival (p = 0.017). The multivariate analysis by Cox proportional hazard regression model showed that stage I STAS+ lung adenocarcinoma patients with lymphatic vessel invasion (HR: 1.711, 95% CI: 1.052-2.784; p = 0.045), vascular invasion (HR: 5.014, 95% CI: 3.154-7.969; p < 0.001), and visceral pleural invasion (HR: 2.086, 95% CI: 1.162-3.743; p = 0.014), and without ACT (HR: 1.675, 95% CI: 1.043-2.689; p = 0.033) had a significant survival disadvantage. Conclusion: ACT can boost the postoperative survival of patients with stage I (STAS+) lung adenocarcinoma.

Curcumin Improves Keratinocyte Proliferation, Inflammation, and Oxidative Stress through Mediating the SPAG5/FOXM1 Axis in an In Vitro Model of Actinic Dermatitis by Ultraviolet.

Background: Chronic actinic dermatitis (CAD) is an abnormally proliferating photoallergic skin disease. Dysregulated inflammation and oxidative stress are the immediate factors in the abnormal proliferation of keratinocytes. This study aimed to investigate the effect of curcumin on the aberrant proliferation of keratinocytes in an in vitro (actinic dermatitis) AD model and the possible molecular mechanisms. Methods: The keratinocytes were irradiated with ultraviolet (UV) to construct an in vitro AD model and then processed with different concentrations of curcumin. Cell viability, oxidative stress markers (SOD, GSH-PX, and MDA), activated oxygen species (ROS), and inflammation markers (IL-1ß, IL-6, IL-18, and TNFα) were determined, respectively. Western blot was applied to assay the profiles of apoptosis-related proteins (Bax, Bcl-xL, Caspase3, Caspase8, and Caspase9), oxidative stress proteins (Keap1, Nrf2, HO-1, COX2, and iNOS), and inflammatory proteins (NF-κB, MMP1, and MMP9) and SPAG5/FOXM1. Functionally, SPAG5 or FOXM1 overexpression and knockdown models were constructed in keratinocytes to characterize their influence on UV irradiation-mediated keratinocyte dysfunction. Results: Curcumin weakened UV-mediated inflammation, proliferation, and oxidative stress and impaired apoptosis in keratinocytes. UV boosted SPAG5/FOXM1 expression in cells, while curcumin concentration-dependently retarded SPAG5/FOXM1 expression. Overexpression of SPAG5/FOXM1 fostered UV-mediated inflammation, proliferation, oxidative stress, and intensified apoptosis, whereas curcumin mostly reversed the SPAG5/FOXM1-mediated effects. In addition, knocking down SPAG5/FOXM1 ameliorated UV-mediated keratinocyte dysfunction, whereas curcumin failed to exert further protective effects in cells with knockdown of SPAG5/FOXM1. Conclusion: Curcumin modulated proliferation, inflammation, oxidative stress, and apoptosis of keratinocytes by restraining the SPAG5/FOXM1 axis.

Assessment of Carbon Nanoparticle Suspension Lymphography-Guided Distal Gastrectomy for Gastric Cancer.

Importance: Carbon nanoparticle suspension injection (CNSI) can be used to visualize lymph node (LN) drainage in gastric cancer. The tracing and diagnostic value of carbon nanoparticle suspension lymphography-guided distal gastrectomy for gastric cancer has not been thoroughly reported. Objective: To compare the number of lymph nodes identified in patients with gastric cancer receiving a CNSI vs no injection. Design, Setting, and Participants: This is a retrospective cohort study including patients with clinical T1 to T4 disease who underwent laparoscopic or robotic distal gastrectomy. Data from a cohort of 1225 patients at the Fourth Hospital of Hebei Medical University (Shijiazhuang, China) from November 2019 to February 2021 were analyzed. Patients were divided into the CNSI group and conventional group after 1:1 propensity matching analysis. The mean number of LNs detected was compared between groups, and the diagnostic role of CNSI was analyzed in the CNSI group. Statistical analysis was performed from May to July 2021. Exposure: CNSI was peritumorally injected under an endoscope 1 day before surgery in the CNSI group, and the conventional group did not receive any treatment before surgery. Main Outcomes and Measures: The main outcome was the number of LNs detected. Gastrectomy with systematic D1+ (ie, stations 1, 3, 4sb, 4d, 5, 6, and 7) or D2 (ie, all D1 stations, plus 8a, 9, 11p, and 12a) lymphadenectomy was performed. Black-stained LNs and nonblack-stained LNs were examined separately in the CNSI group. Results: A total of 312 consecutive patients (mean [SD] age, 56.7 [10.4] years; 216 [69.2%] men) who underwent distal gastrectomy were enrolled, including 78 patients in the CNSI group, and another 78 patients determined from 1:1 propensity score matching, making an overall cohort size of 156 patients. The mean (SD) number of LNs detected in the CNSI group was 59.6 (21.4), which was significantly higher than that in the conventional group (30.0 [11.3] LNs; P < .001). In the CNSI group, the mean (SD) number of LNs detected at black-stained LN stations was significantly higher than that at nonstained LN stations (9.2 [6.1] LNs per station vs 3.5 [3.2] LNs per station; P < .001). For black-stained LN stations, the sensitivity was 97.8% (95% CI, 91.6%-99.6%), specificity was 38.1% (95% CI, 34.2%-42.3%), positive predictive value was 20.1% (95% CI, 16.6%-24.2%), and negative predictive value was 99.1% (95% CI, 96.4%-99.8%); for the black-stained LNs, sensitivity was 97.6% (95% CI, 95.3%-98.8%), specificity was 35.4% (95% CI, 33.9%-36.8%), positive predictive value was 11.6% (95% CI, 10.5%-12.8%), and negative predictive value was 99.4% (95% CI, 98.8%-99.7%). Conclusions and Relevance: These findings suggest that CNSI was associated with facilitating the dissection of all positive LNs, which could improve surgical quality. Carbon nanoparticle suspension-guided lymphography may be an alternative to conventional systematic lymphadenectomy for distal gastrectomy.

Application Value of PET/CT and MRI in the Diagnosis and Treatment of Patients With Synchronous Multiple Pulmonary Ground-Glass Nodules.

Background: Synchronous multiple ground-glass nodules (SMGGNs) in synchronous multiple lung cancers are associated with specific imaging findings. It is difficult to distinguish whether multiple nodules are primary tumors or metastatic lesions in the lungs. The need for PET/CT and contrast-enhanced brain MRI for these patients remains unclear. This study investigated the necessity of these two imaging examinations for SMGGN patients by means of retrospective analysis. Methods: SMGGN patients who were diagnosed and treated in our hospital from October 2017 to May 2020 and underwent whole-body PET/CT(Cranial excepted) and/or contrast-enhanced brain MRI+DWI were enrolled in this study. We analyzed the imaging and clinical characteristics of these patients to evaluate SMGGN patients' need to undergo whole-body PET/CT and brain MRI examination. Results: A total of 87 SMGGN patients were enrolled. 51 patients underwent whole-body PET/CT examinations and did not show signs of primary tumors in other organs, metastatic foci in other organs, or metastasis to surrounding lymph nodes. 87 patients underwent whole-brain MRI, which did not reveal brain metastases but did detect an old cerebral infarction in 23 patients and a new cerebral infarction in one patient. 87 patients underwent surgical treatment in which 219 nodules were removed. All nodules were diagnosed as adenocarcinoma or atypical adenomatous hyperplasia. No lymph node metastasis was noted. Conclusion: For SMGGN patients, PET/CT and enhanced cranial MRI are unnecessary for SMGGNs patients, but from the perspective of perioperative patient safety, preoperative MRI+DWI examination is recommended for SMGGNs patients.

Risk factors for lymph node metastasis and prognosis in colorectal neuroendocrine tumours.

PURPOSE: The detection rate of colorectal neuroendocrine tumours (CR-NETs) is increasing, but their treatment is still controversial. Lymph node metastasis is an important reference index for the selection of treatment. The aim of our study was to investigate the factors associated with lymph node metastasis and prognosis of CR-NETs. METHODS: The case characteristics of patients with colorectal neuroendocrine tumours from January 2011 to December 2020 were retrospectively analysed, including age, gender, tumour size, tumour location, lymph node metastasis, pathological grade and follow-up. RESULTS: A total of 195 cases of CR-NETs were included in this study. When 15 mm was used as the cut-off value, the sensitivity, specificity and area under the curve (AUC) of lymph node metastases were 95.9%, 95.2% and 0.986, respectively. Multivariate analysis suggested that tumour size ≥ 15 mm (OR: 30.517, 95% CI: 1.250 ~ 744.996, p = 0.036) and lymphovascular invasion (OR: 42.796, 95% CI: 2.882 ~ 635.571, p = 0.006) were independent risk factors for lymph node metastasis. Age ≥ 56 (HR: 7.434, 95% CI: 1.334 ~ 41.443, p = 0.022) and distant metastasis (HR: 24.487, 95% CI: 5.357 ~ 111.940, p < 0.001) were independent prognostic factors in multivariable analyses. CONCLUSIONS: When the size of a CR-NET is ≥ 15 mm, the risk of lymph node metastasis is higher, and it is recommended to choose the surgical method carefully. Tumour size and lymphovascular invasion were independent risk factors for lymph node metastasis. Age ≥ 56 and distant metastasis were independent prognostic factors.

Curcumin protection against ultraviolet-induced photo-damage in Hacat cells by regulating nuclear factor erythroid 2-related factor 2.

Curcumin suppressed ultraviolet (UV) induced skin carcinogenesis and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. However, whether curcumin protects skin injury caused by UV is still unknown. A vitro model was established and curcumin effects on Hacat cells were detected. Nrf2 was knocked down in Hacat cells to verify the Nrf2 role in the protective effect of curcumin. Results indicated that ultraviolet A (UVA) (or ultraviolet B (UVB)) irradiation would lead to decreased cell proliferation, increased cell apoptosis, decreased catalase, heme oxygenase 1, and superoxide dismutase expression, and increased levels of protein carbonylation and malondialdehyde (p < 0.05). These adverse events could be reversed by adding 5-µM curcumin. Meanwhile, we found that the application of curcumin effectively induced Nrf2 nuclear accumulation in Hacat cells. While in the Nrf2 knockdown cells, the protective effects of curcumin against UVA (or UVB) were attenuated. Conclusively, curcumin protects Hacat cells against UV exposure-induced photo-damage by regulating Nrf2 expression.

Primary pulmonary meningiomas: report of two cases and review of the literature.

BACKGROUND: Meningiomas rarely occur outside the skull, and primary pulmonary meningiomas (PPMs) are more rare. Only a few cases have been reported in the literature. The clinicopathological characteristics are not clear and it is easy to be misdiagnosed, so it is very important to master its diagnosis and differential diagnosis. METHODS: We report two women with primary pulmonary meningioma. At the time of physical examination, the small solitary pulmonary nodules were detected on chest radiograph, and wedge resection was performed by Video-assisted Thoracoscope Surgery(VATS), and histologic evaluation showed that the lesions were benign PPMs. The clinicopathological features, immunophenotype and differential diagnosis of PPMs were analyzed, with a review of the cases published in the literature. RESULTS: The study group comprised of 40 patients, 14 males and 26 females. The median age was 56.5 years (range 18-108). Thirty patients who underwent routine screening studies were asymptomatic but had a pulmonary nodule detected on chest X-ray. Nine patients had respiratory symptoms. Only 1 patient had non-specific symptoms. Most of the PPMs were benign, only 3 cases were malignant. Benign PPMs ranged from 0.6 cm to 6 cm in diameter (median 2 cm). The 3 malignant PPMs were 5 cm, 6.5 cm and 15 cm in diameter. The prognosis of benign PPM resection is good, with almost no recurrence or metastasis. But the two of three malignant PPMs relapsed. CONCLUSIONS: PPM is very rare. It needs to be diagnosed by combining histology and immunohistochemistry. Diseases that need to be identified include spindle cell mesothelioma, spindle cell thymoma, spindle cell carcinoma, metastatic tumor, etc.

A case of different gene mutations in primary and metastatic lesions after EGFR-TKI treatment of lung cancer.

BACKGROUND: It remains controversial whether patients with EGFR-mutant lung adenocarcinoma should stop using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after progression during treatment. CASE REPORT: We report a 35-year-old man with poorly differentiated adenocarcinoma of the left upper lobe and an exon 19 deletion (Ex19Del) mutation found by large-panel next-generation sequencing. The patient underwent video-assisted thoracoscopic surgery 12 months after oral administration of icotinib 125 mg tid, and the left upper lobe and surrounding lymph nodes were removed. Postoperative pathology supported a diagnosis of left upper lobe adenocarcinoma and subcarinal (1/2), main pulmonary artery window (1/2), and left hilar (1/2) lymph node metastases. The EGFR mutations in the residual lesions had disappeared, and Ex19Del mutations were still visible in the mediastinal lymph node metastasis. CONCLUSION: Spatial heterogeneity of the resistance mechanism may explain why patients who continue to receive EGFR-TKIs in combination with local therapies (e.g., radiotherapy) for progressing lesions may benefit even after progression during EGFR-TKI therapy. The loss of the EGFR mutation allele as a putative resistance mechanism requires additional preclinical and clinical confirmation.

Comparison detection methods for EGFR in formalin-fixed paraffin-embedded tissues of patients with NSCLC.

Epidermal growth factor receptor (EGFR) is an important gene in the development of lung cancer. Non-small cell lung cancer (NSCLC) is the most common lung cancer. In the present study, the expression of EGFR in 717 patients with NSCLC was detected by Ventana automatic immunohistochemical technique, and the samples was verified by Real-time PCR, and then the results were compared with the data acquired by next-generation sequencing technology (NGS), which is the high throughput, multiple sites for EGFR gene mutation testing. The expression of Ventana EGFR in 717 cases of NSCLC was detected by immunohistochemistry, and the positive rate was 60.70 % (435 / 717). The mutation rate of EGFR was 57.60 % (413/717). The coincidence rate of Ventana EGFR immunohistochemical assay and Real-time PCR assay reached 94.94 %, and the two had high consistency. The coincidence rate of Ventana EGFR immunohistochemical assay and NGS were high correlation. Based on these results, Ventana EGFR automatic immunohistochemical detection has high accuracy, simple operation process, low price and easy interpretation. It can be used as the preferred method for EGFR detection.

Influential factors and prognostic analysis of blood vessel invasion in advanced gastric cancer.

The purpose of this study was to analyze the influencing factors of BVI in advanced gastric cancer and explore the factors affecting the prognosis of advanced gastric cancer, so as to accurately evaluate the disease status and enable patients to receive effective treatment. We retrospectively analyzed 622 cases with complete data and successful follow-up. BVI was found in 144 of the 622 patients with advanced gastric cancer, with a detection rate of 23.15%. BVI was closely related to the differentiation degree, infiltration depth and lymph node metastasis of advanced gastric cancer, (P <  0.05). Gender, age, tumor location, tumor size, Lauren classification, tumor M stage, and clinical TNM stage were not the influencing factors of BVI in patients with advanced gastric cancer (P >  0.05). The 5-year survival rate of patients in the positive group of BVI was 34.72%. The 5-year survival rate of patients with advanced gastric cancer was correlated with BVI, Lauren classification, depth of invasion, lymph node metastasis, and clinical TNM staging, (P <  0.05). The 5-year survival rate was independent of gender, age, tumor location, tumor size, tumor tissue differentiation, and M stage (P >  0.05). The results of multi-factor analysis showed that BVI, N stage and clinical TNM stage were independent predictors of prognosis in patients with advanced radical gastric cancer. By analyzing the stage and related prognostic factors of resectable advanced gastric cancer, we found that BVI was not only closely related to lymph node metastasis, but also an independent predictor of prognosis of advanced gastric cancer. As this study was only a single-center retrospective study, there may be a selective bias in clinical data. So large-scale and multi-center collaboration is needed to further explore the influencing factors of BVI in the progression of gastric cancer.

Clinical observation of crizotinib in the treatment of ALK-positive advanced non-small cell lung cancer.

BACKGROUND: ALK is a prognostic and predictive tumor marker in non-small cell lung carcinoma (NSCLC), and is more often found in lung adenocarcinomas. METHODS: The clinical and pathological data of 87 patients confirmed to have NSCLC by pathology or cytology were selected from April 2014 to January 2017 at the Tumor Hospital of Hebei Province. RESULTS: Of the 87 ALK-positive-patients, 47 patients were treated with oral administration of crizotinib. The objective response rate (ORR) was 61.7%, the disease control rate (DCR) was 93.6%, and the mPFS was 19 months. In an analysis of the number of metastatic sites, the patients who had more than three metastatic sites, the ORR, DCR, and mPFS were 63.9%, 94.5%, and 19 months, compared with the 45.5%, 91%, and 11 months in the patients with less sites (P = 0.040). For patients of 60 years or older, ORR and DCR were 40% and 100%, the other group was 71.9% and 90.6%, respectively(P = 0.036). The timing of treatment was analyzed. At the first application of crizotinib, ORR and DCR were 78.2% and 100% corresponding 45.8% and 87.5% at the second and final application of crizotinib group (P = 0.022). Baseline brain metastases were present in 25.5% (12/47) of patients in this study. 9 of the patients who developed disease progression during crizotinib treatment had new brain metastases or increased preexisting cranial foci. Most of them took the treatment strategy of continuing crizotinib or replacing the second/third generation ALK-TKI treatment combined with local radiotherapy for brain metastases. CONCLUSIONS: The efficacy of crizotinib in patients with advanced NSCLC is related to the number of metastatic organs, age and timing of treatment. The use of crizotinib is prone to intracranial progression, and progression of simple brain metastases is not an indication that crizotinib is discontinued. Patients will continue to benefit from combination of local radiotherapy.

Intratumoral heterogeneity of esophageal squamous cell carcinoma and its clinical significance.

Recent studies have shown that intratumoral heterogeneity is prevalent in esophageal squamous cell cancer (ESCC) based on DNA sequencing and chromosome analysis in multiple regions from the same tumor. This study aimed to investigate the expression of ZNF750, EP300, MTOR and KMT2D and their intratumoral heterogeneity (ITH) in patients with ESCC. A total of 106 cases, who underwent esophagectomy from 2008 to 2010, with two foci from each case, were tested by immunohistochemistry(IHC) as well as 12 cases were tested by RNAscope in this study.We found that 58/106 (54.72%), 66/106 (62.26%), 75/106 (70.75%%) of ESCC showed high expression of ZNF750, EP300, MTOR, respectively by IHC, and 8/12 (66.67%), 10/12 (83.33%), 4/12 (33.33%) and 6/12 (50%) showed high expression of ZNF750, EP300, MTOR and KMT2D, respectively by RNAscope. Multivariate analysis showed that MTOR expression was an independent infavorable prognostic factor of overall survival (OS) (HR = 1.921; P = 0.000). This study also found that 44/106(4151%), 37/106 (34.91%), 39/106(36.79%) of ESCC showed heterogeneous expression of ZNF750, EP300 and MTOR respectively by IHC, 8/12(66.67%), 8/12(66.67%), 4/12(33.33%), 4/12(33.33%) of ZNF750, EP300, MTOR and KMT2D respectively by RNAscope, IHC and RNAscope could successfully detect a high prevalence of ITH. In conclusion, findings of this study showed that ZNF750, EP300, MTOR and KMT2D heterogeneously expressed in ESCC. High expression of ZNF750 related to a better outcome, while EP300 and MTOR related to a poor prognosis.

Lung adenocarcinoma with concurrent ALK and ROS1 rearrangement: A case report and review of the literatures.

ALK and ROS1 are prognostic and predictive tumor markers in non-small cell lung carcinoma (NSCLC), which are more often found in lung adenocarcinomas as with other oncogenes such as EGFR, KRAS, or C-MET. Their positivity is 2.6% and 1.3%, respectively, and patients who have mutations in both genes are extremely rare. Here, we report a 61-year-old male diagnosed with acinar adenocarcinoma, who was shown to have both ALK and ROS1 rearrangements but was EGFR- and C-MET mutation-negative. He was treated surgically and received targeted therapy. Our review of the literature revealed that few such cases of concurrent ALK and ROS1 rearrangements have been reported. This information furthers our understanding of the molecular biology underlying NSCLC which will aid the selection of optimal treatment for patients with more than one driver mutation.