The efficacy and safety of vincristine, irinotecan and anlotinib in Epithelioid Sarcoma.

BACKGROUND: Epithelioid sarcoma is a rare soft tissue sarcoma characterized by SMARCB1/INI1 deficiency. Much attention has been paid to the selective EZH2 inhibitor tazemetostat, where other systemic treatments are generally ignored. To explore alternative treatment options, we studied the effects of irinotecan-based chemotherapy in a series of epithelioid sarcoma patients. METHODS: We retrospectively reviewed data from patients with metastatic or unresectable epithelioid sarcoma at the Peking University People's Hospital treated with irinotecan (50 mg/m2/d d1-5 Q3W) in combination with Anlotinib (12 mg Qd, 2 weeks on and 1 week off) from July 2015 to November 2021. RESULTS: A total of 54 courses were administered. With a median follow up of 21.2 months (95% CI, 12.2, 68.1), the 5-year overall survival rate was 83.3%. Five of eight (62.5%) patients presented with unresectable localized lesions, including local tumor thrombosis and lymphatic metastasis. The other patients had unresectable pulmonary metastases. Six of eight (75%) patients had progressed following two lines of systemic therapy. The objective response rate reached 37.5% (three of eight patients) while stabilized disease was observed in 62.5% (five of eight) of patients. No patient had progressed at initial evaluation. At the last follow up, two patients were still using the combination and three patients had ceased the therapy due to toxicities such as diarrhea, nausea, and emesis. One patient changed to tazemetostat for maintenance and one patient stopped treatment due to coronavirus disease 2019 (COVID-19). Another patient stopped therapy as residual lesions had been radiated. CONCLUSIONS: The combination of irinotecan and Anlotinib as a salvage regimen may be considered another effective treatment option for refractory epithelioid sarcoma. TRIAL REGISTRATION: This study was approved in the Medical Ethics Committee of Peking University People's Hospital on October 28, 2022 (No.: 2022PHD015-002). The study was registered in Clinicaltrials.gov with identifier no. NCT05656222.

Two-step osteotomy/discectomy through cannulated screw (TOCS) technique for en bloc resection of spine tumor: surgical technique and preliminary results.

PURPOSE: We have developed a novel technique for osteotomy/discectomy during en bloc resection of spine tumors named two-step osteotomy/discectomy through cannulated screw (TOCS). This study aims at describing the procedure of TOCS technique and assessing its efficiency and safety. METHODS: We retrospectively reviewed fourteen patients who underwent en bloc resection for spine tumors using TOCS technique in our center between August 2018 and September 2022. The technique was based on a specially designed "slotted" cannulated screw which was a cannulated screw with a longitudinal slot to provide the accessibility of T-saw. During osteotomy/discectomy, the "slotted" cannulated screw was inserted obliquely along the plane between the dura and the posterior wall of spine in light of the planned osteotomy/discectomy plane under routine fluoroscopic imaging guidance. The T-saw was introduced through the screw, and the osteotomy/discectomy was performed sequentially in two steps under the guidance of the screw by turning the slot away and toward the dura. The intra-/perioperative complication, neurological function (determined by Frankel grading), surgical margin (determined by a pathologist using AJCC R system), follow-up details were documented. RESULTS: The mean duration of surgery was 599.3 (360-890) min with a mean volume of intra-operative hemorrhage of 2021.4 (800-5000) mL. The intra-/perioperative complications were found in four patients (28.6%). R0 and R1 resections were achieved in nine and five patients, respectively. There was no R2 resection. After a mean follow-up period of 30.6 (10-67) months, all patients were alive except one patient died ten months after surgery due to unrelated cause. No recurrence and implant failure were found. Thirteen patients (92.9%) exhibited completely normal neurological function same as their preoperative neurological status. CONCLUSION: Using TOCS technique can facilitate a precise, complete and safe osteotomy/discectomy procedure during en bloc resection for spine tumor without the aid of intra-operative navigation.

Exploratory study of an anti-PD-L1/TGF-ß antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02).

BACKGROUND: Novel and effective immunotherapies are required for refractory or recurrent sarcomas. Transforming growth factor-beta (TGF-ß) is a diverse regulatory and fibrogenic protein expressed in multiple sarcoma tumors that promotes epithelial-mesenchymal transition and excessive deposition of extracellular matrix. This study evaluated the efficacy and safety of the anti-PD-L1/TGF-ß antibody TQB2858 in patients with refractory osteosarcoma and alveolar soft part sarcoma (ASPS). METHODS: This single-arm phase 1b exploratory study included patients with refractory osteosarcoma or ASPS who had previously undergone at least two lines of systemic therapy. Patients were administered 1200 mg of TQB2858 once every 3 weeks. The primary endpoint was objective response rate (ORR), with null and alternative hypotheses of ORR ≤5% and ≥20%, respectively. Exploratory biomarker analyses using immunohistochemistry (IHC) staining (for PD-L1 and TGF-ß) were performed on pre-treatment tumor samples. RESULTS: Eleven eligible patients were included in this study. TQB2858 did not demonstrate evidence of efficacy as 0/5 osteosarcomas had any objective response, while 2/6 ASPS showed a partial response. The median progression-free survivals were 1.51 (1.38, Not Evaluable) and 2.86 (1.38, Not Evaluable) months for the osteosarcoma and ASPS groups, respectively. None of the administered cycles met the criteria for unacceptable toxicity. Other Grade 3 toxicities included abnormal liver function and elevation of γ-glutamyl transferase. IHC analysis revealed that functional enrichment in the TGF-ß pathway or PD-L1 was not associated with treatment outcomes. CONCLUSIONS: The combination of PD-L1 and TQB2858 did not significantly improve the ORR in patients with recurrent osteosarcoma. However, it improved immunogenic responses in ASPS, even after progression upon anti-PD-1/PD-L1 therapy, with an acceptable safety profile. IHC profiling with pathway enrichment analysis may not have any predictive value for survival outcomes. TRIAL REGISTRATION: Prospectively registered in the Ethical Review Committee of Peking University People's Hospital. The trial registration number is 2021PHA105-001 and 2021PHA140-001 and the registration date was March 2, 2022. CLINICALTRIALS: gov Identifier CTR20213001 and CTR20220390.

Morphological, immunohistochemical, and genetic analyses of epithelioid gastrointestinal stromal tumors.

Epithelioid gastrointestinal stromal tumors (GISTs) are rare and may be confused with other tumors with epithelioid morphology. Therefore, herein, we collected 12 epithelioid GIST samples and summarized their morphological and immunohistochemical characteristics. Through genetic testing, we explored the correlation between morphology and gene mutations. The results showed that eight tumors showed focal or diffuse myxoid stromal changes with less cohesively arranged rhabdoid tumor cells; among these, five showed platelet-derived growth factor receptor alpha gene (PDGFRA) mutations. Signet ring cells with sclerosing stroma and receptor tyrosine kinase type III gene (KIT) mutations were present in two cases, which might be a KIT mutation-associated growth pattern in epithelioid GISTs. Succinate dehydrogenase gene (SDH) mutations were detected in three cases. Simultaneously, PDGFRA mutations were detected in two cases, and the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation was detected in another case. SDH-subunit B (SDHB) expression was partially weak and strongly diffuse in two cases with concurrent PDGFRA and SDHD mutations, respectively. The coexistence of PDGFRA and SDHD mutations may have affected SDHB expression. Altogether, we concluded that PDGFRA mutations may play an important role in co-mutant GIST pathogenesis.

Complete remission of metastatic osteosarcoma using combined modality therapy: a retrospective analysis of unselected patients in China.

BACKGROUND: Complete surgical remission (CSR) is the best predictor of overall survival (OS) for patients with metastatic osteosarcoma. However, metastasectomy has not been widely implemented in China in the last decade due to various factors, and instead, most physicians choose hypofractionated radiotherapy to treat pulmonary lesions. This study aimed to retrospectively evaluate the outcomes of different local treatments for pulmonary lesions and identify the best local therapy strategies for these patients. METHODS: We reviewed the clinical courses of osteosarcoma patients with pulmonary metastases who were initially treated in two sarcoma centres in Beijing, China, from June 1st, 2009, to March 26th, 2020. With a median follow-up of 32.4 (95% confidence interval (CI): 30.8, 36.1) months, a total of 127 patients with 605 pulmonary nodules, all of whom had received local therapy and firstly achieved CSR or complete radiated/metabolic remission (CRR), were included in the analysis. A total of 102 patients with 525 nodules were initially diagnosed with resectable lung metastases, while 25 patients had 80 indeterminate nodules at presentation and relapsed with pulmonary metastases within 6 months after the completion of adjuvant chemotherapy. RESULTS: Eighty-eight of 127 (69.3%) patients had fewer than 5 nodules at the time of local therapy, with 48 of 127 (37.8%) located in the unilateral pleura. No patient underwent thoracotomy, and 42 of 127 patients (85 nodules) received video-assisted thoracoscopic surgery (VATS). In addition, 79 of 127 patients (520 nodules) received hypofractionated stereotactic body radiotherapy (RT), such as Gamma Knife radiosurgery or CyberKnife radiosurgery. The twelve-month event-free survival (EFS) (from local therapy to progression) rate of this entire study cohort was 35.6% (95% CI: 26.8, 44.4%), without a significant difference between the two groups (44.7% for VATS vs. 28.4% for RT, P = 0.755). Radiation-induced pneumonitis was observed in 62 of 86 (72.1%) patients, with one patient (1/86, 1.2%) in grade 4. CONCLUSIONS: Our past data showed a similar prognosis with the use of hypofractionated radiotherapy and VATS for the treatment of pulmonary metastasis and no inferiority to thoracotomy regarding historical outcomes. Currently, high-resolution chest computed tomography (CT) provides sufficient information on nodules, and less invasive modalities can thus be considered for treatment.

Genomic characterisation of pulmonary subsolid nodules: mutational landscape and radiological features.

BACKGROUND: Lung adenocarcinomas (LUADs) that display radiologically as subsolid nodules (SSNs) exhibit more indolent biological behaviour than solid LUADs. SSNs, commonly encompassing pre-invasive and invasive yet early-stage adenocarcinomas, can be categorised as pure ground-glass nodules and part-solid nodules. The genomic characteristics of SSNs remain poorly understood. METHODS: We subjected 154 SSN samples from 120 treatment-naïve Chinese patients to whole-exome sequencing. Clinical parameters and radiological features of these SSNs were collected. The genomic landscape of SSNs and differences from that of advanced-stage LUADs were defined. In addition, we investigated the intratumour heterogeneity and clonal relationship of multifocal SSNs and conducted radiogenomic analysis to link imaging and molecular characteristics of SSNs. Fisher's exact and Wilcoxon rank sum tests were used in the statistical analysis. RESULTS: The median somatic mutation rate across the SSN cohort was 1.12 mutations per Mb. Mutations in EGFR were the most prominent and significant variation, followed by those in RBM10, TP53, STK11 and KRAS. The differences between SSNs and advanced-stage LUADs at a genomic level were unravelled. Branched evolution and remarkable genomic heterogeneity were demonstrated in SSNs. Although multicentric origin was predominant, we also detected early metastatic events among multifocal SSNs. Using radiogenomic analysis, we found that higher ratios of solid components in SSNs were accompanied by significantly higher mutation frequencies in EGFR, TP53, RBM10 and ARID1B, suggesting that these genes play roles in the progression of LUADs. CONCLUSIONS: Our study provides the first comprehensive description of the mutational landscape and radiogenomic mapping of SSNs.

Multiple primary tumors: a case report and review of the literature.

BACKGROUND: Multiple primary tumors, especially quadruple primary neoplasms is extremely rare. Fibrous dysplasia (FD), osteosarcoma (OS), and giant cell tumor of bone (GCTB) are three bone tumors with low incidence while primary pulmonary meningioma is a rare disease. In this case report, we present a unique synchronous occurrence of these four separate pathological conditions. CASE PRESENTATION: A 53-year-old male previously underwent resection of OS of fifth rib and FD of eighth rib 1 year ago. Recently, a discontinuous pain at right knee developed. Serial X-ray films showed a progressively pure osteolytic lesion of proximal tibia which extended gradually. The incisional biopsy revealed that this tumor was confirmed as GCTB, and the tumor was successfully managed by extensive curettage and bone cement filling. The diagnosis of GCTB was re-confirmed by the postoperative histopathologic examinations. High-throughput sequencing from the GCTB exhibited a somatic mutation of H3.3A (G35W exon2). Germline testing revealed a germ-cell variant in gene of BRCA2 (exon 8 V220Ifs*4). CONCLUSIONS: This is a unique case with quadruple primary tumors. Germline mutation in gene of BRCA2 may be associated with the occurrence of multiple primary tumors in this patient.

Cytological and Proteomic Analysis of Wheat Pollen Abortion Induced by Chemical Hybridization Agent.

In plants, pollen grain transfers the haploid male genetic material from anther to stigma, both between flowers (cross-pollination) and within the same flower (self-pollination). In order to better understand chemical hybridizing agent (CHA) SQ-1-induced pollen abortion in wheat, comparative cytological and proteomic analyses were conducted. Results indicated that pollen grains underwent serious structural injury, including cell division abnormality, nutritional deficiencies, pollen wall defect and pollen grain malformations in the CHA-SQ-1-treated plants, resulting in pollen abortion and male sterility. A total of 61 proteins showed statistically significant differences in abundance, among which 18 proteins were highly abundant and 43 proteins were less abundant in CHA-SQ-1 treated plants. 60 proteins were successfully identified using MALDI-TOF/TOF mass spectrometry. These proteins were found to be involved in pollen maturation and showed a change in the abundance of a battery of proteins involved in multiple biological processes, including pollen development, carbohydrate and energy metabolism, stress response, protein metabolism. Interactions between these proteins were predicted using bioinformatics analysis. Gene ontology and pathway analyses revealed that the majority of the identified proteins were involved in carbohydrate and energy metabolism. Accordingly, a protein-protein interaction network involving in pollen abortion was proposed. These results provide information for the molecular events underlying CHA-SQ-1-induced pollen abortion and may serve as an additional guide for practical hybrid breeding.

Signaling protein signature predicts clinical outcome of non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is characterized by abnormalities of numerous signaling proteins that play pivotal roles in cancer development and progression. Many of these proteins have been reported to be correlated with clinical outcomes of NSCLC. However, none of them could provide adequate accuracy of prognosis prediction in clinical application. METHODS: A total of 384 resected NSCLC specimens from two hospitals in Beijing (BJ) and Chongqing (CQ) were collected. Using immunohistochemistry (IHC) staining on stored formalin-fixed paraffin-embedded (FFPE) surgical samples, we examined the expression levels of 75 critical proteins on BJ samples. Random forest algorithm (RFA) and support vector machines (SVM) computation were applied to identify protein signatures on 2/3 randomly assigned BJ samples. The identified signatures were tested on the remaining BJ samples, and were further validated with CQ independent cohort. RESULTS: A 6-protein signature for adenocarcinoma (ADC) and a 5-protein signature for squamous cell carcinoma (SCC) were identified from training sets and tested in testing sets. In independent validation with CQ cohort, patients can also be divided into high- and low-risk groups with significantly different median overall survivals by Kaplan-Meier analysis, both in ADC (31 months vs. 87 months, HR 2.81; P <  0.001) and SCC patients (27 months vs. not reached, HR 9.97; P <  0.001). Cox regression analysis showed that both signatures are independent prognostic indicators and outperformed TNM staging (ADC: adjusted HR 3.07 vs. 2.43, SCC: adjusted HR 7.84 vs. 2.24). Particularly, we found that only the ADC patients in high-risk group significantly benefited from adjuvant chemotherapy (P = 0.018). CONCLUSIONS: Both ADC and SCC protein signatures could effectively stratify the prognosis of NSCLC patients, and may support patient selection for adjuvant chemotherapy.

Overexpression of GPNMB predicts an unfavorable outcome of epithelial ovarian cancer.

OBJECTIVE: Glycoprotein non-metastatic protein B (GPNMB) is a transmembrane glycoprotein that is expressed at higher levels in several malignant human tissues than those in matched normal tissues. Thus, GPNMB may serve as an attractive therapeutic target of cancer treatment. In this study, the prognostic value of GPNMB expression was examined in tumors derived from a cohort of patients with epithelial ovarian cancer (EOC). METHODS: GPNMB expression in matched formalin-fixed and paraffin-embedded tissue samples was evaluated by immunohistochemistry (IHC), whereas GPNMB mRNA expression in fresh-frozen biopsy tissues was detected using real-time quantitative PCR (qPCR). Meanwhile, the correlations of GPNMB expression with the clinical characteristics of EOC were assessed. Besides, survival data were analysed using Kaplan-Meier and Cox regression analyses, respectively. RESULTS: GPNMB expression was remarkably upregulated in EOC tissues compared with that in normal ovarian controls at both mRNA and protein levels. In addition, abundant GPNMB expression in EOC was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001), residual tumor (P = 0.036), and lymph node metastasis (P = 0.004). Furthermore, results of univariate and multivariate analyses indicated that GPNMB expression level was an independent prognostic factor of the progression-free survival (PFS) and overall survival (OS) (P < 0.001 and P < 0.001, respectively) for EOC patients. CONCLUSION: Upregulated GPNMB levels in EOC patients are associated with dismal prognosis. Moreover, findings in the current study indicate that GPNMB is a potentially useful prognostic predictor of the therapeutic approaches for EOC.

BMPR2 and HIF1-α overexpression in resected osteosarcoma correlates with distant metastasis and patient survival.

OBJECTIVE: Bone morphogenetic protein receptor 2 (BMPR2) and hypoxia-inducible factor 1-α (HIF1-α) existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown. METHODS: To investigate the clinical significance of BMPR2 and HIF1-α in osteosarcoma, we analyzed their expression levels in 103 osteosarcoma specimens by immunochemistry. Meanwhile, we conducted a follow-up to examine the metastatic behavior and overall survival (OS) of osteosarcoma patients. RESULTS: Among 103 tissues, 61 cases had BMPR2-positive expression and 57 cases had HIF1-α positive expression. A significant correlation was noticed between BMPR2 and HIF1-α expression in osteosarcoma specimens (P=0.035). Receiver-operating characteristic (ROC) curves were calculated to investigate the predictive value of the two markers in tumor metastasis. By means of univariate and multivariate analysis, BMPR2 and HIF1-α expression, as well as higher tumor grade, were identified as significant risk factors for OS in patients with osteosarcoma. Kaplan-Meier survival analysis revealed that the patients with BMPR2 and HIF1-α positive expression had worse OS compared with patients with BMPR2-negative or HIF1-α-negative staining. CONCLUSIONS: It can be concluded that BMPR2 and HIF1-α expression is highly correlated with metastatic behavior in patients with osteosarcoma and can serve as predictive markers for metastasis and OS of these patients.

Postoperative recurrence of desmoid tumors: clinical and pathological perspectives.

BACKGROUND: The clinical features and the pathological changes of desmoid tumors were studied to point out the key factors affecting the recurrence. METHODS: The clinical data and specimens of 56 patients who underwent desmoid tumor resection from 2003 to 2008 were reviewed. Possible clinical factors related to the postoperative recurrence were analyzed statistically. The specimens round the lesions were studied histopathologically. RESULTS: The overall recurrence rate was 39.3%. The postoperative recurrence rate of the patients with negative surgical margins and no tumor invasion of the major vessels and nerves was low (P < 0.05). However, the desmoid tumors could destroy the cortical bone and invade the medullary cavity. CONCLUSIONS: Desmoid tumors were pathologically benign, which could extensively invade tissues around the lesions. The invasion of major vessels and nerves and quality of surgical margins are the key factors for the high postoperative recurrence rate.

[The clinical-radiologic-pathologic features of imported pulmonary histoplasmosis].

OBJECTIVE: To describe the clinical features and treatment of imported pulmonary histoplasmosis and therefore to improve the recognition and differential diagnosis of this disease. METHODS: The clinical data of 3 patients with imported pulmonary histoplasmosis in our hospital were collected and analyzed. Literatures published since 1989 were retrieved with 'pulmonary histoplasmosis' from PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP data, of which all the literatures about imported pulmonary histoplasmosis were reviewed. The clinical manifestations, diagnostic methods and treatment were summarized. RESULTS: All the 3 cases of imported pulmonary histoplasmosis were immunocompetent hosts, all were males, age were from 44-67 years, and had a history of exploring the cave or tunnel inhabited by bats in the epidemic areas. All of them developed influenza-like symptoms varying in severity after the onset of the disease. Pulmonary multiple nodules and mediastinal lymphadenopathy were found on chest images. One patient underwent percutaneous lung biopsy and the other two received video-assisted thoracoscopic lung biopsy. All the 3 patients showed consistent histopathological findings, such as granulomatous inflammation with necrosis. Pathogen culture with lung biopsy in the first case was identified as histoplasma. All the 3 cases were treated with itraconazole, and recovered with good prognosis. Thirteen literatures in English were obtained, which reported 60 cases with imported pulmonary histoplasmosis. Forty-two of them were males, 16 were females and 2 undefined. The range of their age was from 17-64 years. No imported pulmonary histoplasmosis was reported so far in Chinese literature. Common features of imported pulmonary histoplasmosis were consistent with our patients, including epidemiology, influenza-like symptoms and bilateral pulmonary nodules, recovery with or without antifungal therapy. CONCLUSION: The epidemiologic history, influenza-like symptoms and bilateral pulmonary nodules provide valuable diagnostic clues for imported histoplasmosis. Clinical features with pathologic findings and good response to antifungal therapy could make the diagnosis even without pathogen detection if other etiology is unlikely.

Risk factors of recurrence for resected T1aN0M0 invasive lung adenocarcinoma: a clinicopathologic study of 177 patients.

BACKGROUND: This study aimed at identifying risk factors of recurrence for completely resected pathologic T1aN0M0 lung adenocarcinomas. METHODS: We reviewed the records of 177 T1aN0M0 invasive adenocarcinoma patients, and re-classified achieved surgical specimens according to the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification. Impact on recurrence-free survival (RFS) for age, gender, smoking history, lymphovascular invasion (LVI) and new classification was analyzed by log-rank test and Cox regression. Two existing prognostic grouping schemes of new classification were compared, and subsequently, the correlation of high-grade group in the better prognostic grouping model with clinical data was investigated statistically. RESULTS: The 5-year recurrence-free rate was 83.7%. The LVI and new adenocarcinoma classification were significantly associated with 5-year RFS (P = 0.012; P = 0.022, respectively). The designation of papillary predominant subtype in the low-grade group, along with lepidic- and acinar predominant subtype had more prognostic significance than the model of combining papillary-, solid- and micropapillary predominant subtypes as the high-grade group (P = 0.005 versus P = 0.181). This high-grade group has increased risk of recurrence in a multivariate Cox regression (adjusted HR 2.815, 95% CI: 1.239 to 6.397, P = 0.013), and is associated significantly more with male gender (adjusted OR 2.214, 95% CI: 1.050 to 4.668, P = 0.037), and, with borderline significance, the presence of LVI (adjusted OR 2.091, 95% CI: 0.938 to 4.662, P = 0.071). CONCLUSIONS: Our results showed that the solid- and micropapillary predominant subtype of IASLC/ATS/ERS classification remains the only risk factor for post-operative recurrence of T1aN0M0 adenocarcinomas, suggesting that they can be indicators of aggressive tumor behaviors.

Can surgical management of bone metastases improve quality of life among women with gynecologic cancer?

BACKGROUND: The evaluation, counseling, and management of gynecologic patients with bone metastasis remain a challenge for clinicians. In order to critically evaluate the role of surgery, we retrospectively analyzed the records of 18 patients surgically treated for metastatic gynecologic tumors of bone, focusing on quality of life, local tumor control, and survival. METHODS: Eighteen patients underwent surgical procedures for the treatment of bone metastases secondary to gynecologic cancer between September 2003 and April 2012. The primary cancer sites included the uterus (n = 10), the cervix (n = 5), and an ovary (n = 3). Patients were followed for an average period of 13.8 months (range, 2 to 34 months). A visual analog pain scale (VAS) and Eastern Cooperative Oncology Group (ECOG) performance status were evaluated both pre- and postoperatively. RESULTS: The median survival time following diagnosis of bone metastasis was 10.0 months. The mean VAS score was 5.8 preoperatively compared with 2.1, 3 months after surgery. The mean pre and postoperative ECOG performance status grades were 3.1 and 2.3, respectively. CONCLUSIONS: The prognosis of gynecological cancer patients with bone metastasis is poor. Some patients had improvement in their quality of life after surgical intervention for bone metastases; however, novel integrated treatment modalities should be investigated.

Classification of multiple primary lung cancer in patients with multifocal lung cancer: assessment of a machine learning approach using multidimensional genomic data.

Background: Multiple primary lung cancer (MPLC) is an increasingly well-known clinical phenomenon. However, its molecular characterizations are poorly understood, and still lacks of effective method to distinguish it from intrapulmonary metastasis (IM). Herein, we propose an identification model based on molecular multidimensional analysis in order to accurately optimize treatment. Methods: A total of 112 Chinese lung cancers harboring at least two tumors (n = 270) were enrolled. We retrospectively selected 74 patients with 121 tumor pairs and randomly divided the tumor pairs into a training cohort and a test cohort in a 7:3 ratio. A novel model was established in training cohort, optimized for MPLC identification using comprehensive genomic profiling analyzed by a broad panel with 808 cancer-related genes, and evaluated in the test cohort and a prospective validation cohort of 38 patients with 112 tumors. Results: We found differences in molecular characterizations between the two diseases and rigorously selected the characterizations to build an identification model. We evaluated the performance of the classifier using the test cohort data and observed an 89.5% percent agreement (PA) for MPLC and a 100.0% percent agreement for IM. The model showed an excellent area under the curve (AUC) of 0.947 and a 91.3% overall accuracy. Similarly, the assay achieved a considerable performance in the independent validation set with an AUC of 0.938 and an MPLC predictive value of 100%. More importantly, the MPLC predictive value of the classification achieved 100% in both the test set and validation cohort. Compared to our previous mutation-based method, the classifier showed better κ consistencies with clinical classification among all 112 patients (0.84 vs. 0.65, p <.01). Conclusion: These data provide novel evidence of MPLC-specific genomic characteristics and demonstrate that our one-step molecular classifier can accurately classify multifocal lung tumors as MPLC or IM, which suggested that broad panel NGS may be a useful tool for assisting with differential diagnoses.

[Dieulafoy disease of the bronchus: 3 cases report with literature review].

OBJECTIVES: To improve the understanding of bronchial Dieulafoy disease by summarizing the clinical and literature reported cases. METHODS: The clinical data of 3 patients with bronchial Dieulafoy disease diagnosed by pathology from January 1, 2007 to May 31, 2012 in our hospital was collected and summarized. The data of 19 cases from literature case report regarding bronchial Dieulafoy disease both in Chinese and English were also reviewed through databases including Wanfang Data, National Knowledge Infrastructure, National Center for Biotechnology Information and Ovid Technologics from January 1, 2005 to May 31, 2012. The clinical characteristics, diagnosis and treatment of all the 22 cases were summarized and analyzed. RESULTS: The average age of the 22 cases with bronchial Dieulafoy disease was (47 ± 15) years, and the preponderance was in male adults (16/22). Right lung (16/22) was more commonly involved than the left lung (4/22), and rarely in both lungs (2/22). Eight cases had smoking history, and 10 cases had underlying diseases such as tuberculosis.Sudden onset of massive hemoptysis was a common manifestation. Massive or lethal hemorrhage was often caused by biopsy injury. The abnormality of bronchial Dieulafoy disease was usually demonstrated as nodular lesions within the lumen of the bronchus.However, It was unable to determine their originating of the anomalous arteries in half of the cases(11/22). Most anomalous arteries confirmed by pathology were branched from bronchial artery (9/22), and rarely from pulmonary artery (2/22). The definitive diagnosis was made by pathological examination.Selective bronchial artery embolization and pulmonary lobectomy were the major therapeutic strategies, but bleeding may relapse after bronchial artery embolization, and lobectomy of the lung was a cure approach. CONCLUSIONS: Bronchial Dieulafoy disease should be differentiated in patients with massive and unexplained hemoptysis.It takes a very high risk for biopsy, which rarely needs to be implemented. Bronchial arteriography and selective bronchial artery embolization should be promptly carried out to avoid life-threatening hemoptysis.Lobectomy could be an alternative choice for a cure.

[A study on the differential diagnosis of ciliated epithelial cells from Lophomonas blattarum in bronchoalveolar lavage fluid].

OBJECTIVE: To validate the authenticity of the cases diagnosed as pulmonary Lophomonas blattarum infection in literatures and Lophomonas blattarum as a kind of pathogen resulting in pulmonary infection. METHODS: From June 2012 to May 2013, mobile cells with cilia at the anterior end of the cells were observed in BALF from 6 patients with pulmonary disease in our hospital. Morphological feature and ultrastructure of the cells were further investigated by optical microscope and electron microscope to determine the type of the cells referring to literature-published photos of Lophomonas blattarum. Literatures about Lophomonas blattarum infection were searched with keyword Lophomonas blattarum from Wanfang Data, China National Knowledge Infrastructure (CNKI) and PubMed. Diagnostic methods and figures provided by the literature were carefully reviewed, and the accuracy of diagnosis of pulmonary Lophomonas blattarum was identified. RESULTS: Mobile cells found in BALF from the 6 patients in our hospital had the morphological features of bronchial ciliate epithelial cells. A nucleus far from the cilia was observed in the middle or at the bottom of the cytoplasm, and these cells did not display the characteristic cytological structures of Lophomonas blattarum: calyx, perinuclear tubules and axial filament. Diagnosis of pulmonary Lophomonas blattarum reported in literatures so far were all based on the morphological features of mobile cells with a cluster of flagellate at anterior end of the cell by optical microscopy. None of the authors did further exploration on the ultrastructure of such a kind of cells and compared with features of Lophomonas blattarum described in the literature. All the active cells reported in literatures had the identical morphological features to those found in our investigation. CONCLUSION: In the past 20 years, all the diagnosed cases as pulmonary Lophomonas blattarum infection reported in our country were misdiagnosed. Currently, there is no evidence to show Lophomonas blattarum as a pathogen resulting in pulmonary infection.

Tocilizumab (monoclonal anti-IL-6R antibody) reverses anlotinib resistance in osteosarcoma.

Purpose: Anlotinib, a tyrosine kinase inhibitor (TKI) has been in clinical application to inhibit malignant cell growth and lung metastasis in osteosarcoma (OS). However, a variety of drug resistance phenomena have been observed in the treatment. We aim to explore the new target to reverse anlotinib resistance in OS. Materials and Methods: In this study, we established four OS anlotinib-resistant cell lines, and RNA-sequence was performed to evaluate differentially expressed genes. We verified the results of RNA-sequence by PCR, western blot and ELISA assay. We further explored the effects of tocilizumab (anti- IL-6 receptor), either alone or in combined with anlotinib, on the inhibition of anlotinib-resistant OS cells malignant viability by CCK8, EDU, colony formation, apoptosis, transwell, wound healing, Cytoskeletal stain assays, and xenograft nude mouse model. The expression of IL-6 in 104 osteosarcoma samples was tested by IHC. Results: We found IL-6 and its downstream pathway STAT3 were activated in anlotinib-resistant osteosarcoma. Tocilizumab impaired the tumor progression of anlotinib-resistant OS cells, and combined treatment with anlotinib augmented these effects by inhibiting STAT3 expressions. IL-6 was highly expressed in patients with OS and correlated with poor prognosis. Conclusion: Tocilizumab could reverse anlotinib resistance in OS by IL-6/STAT3 pathway and the combination treatment with anlotinib rationalized further studies and clinical treatment of OS.