Case report: the dissociated response and clinical benefit of primary leiomyosarcoma of the bone treated with penpulimab plus lenvatinib after failed multi-line therapy.

Leiomyosarcoma occurring in the bone as primary tumor localization is extremely scarce with limited cases described in the literature, accounting for less than 0.7% of all primary bone malignancies. Once distant metastasis occurs, patients have limited treatments and often a somber prognosis, which underscore the need for innovative and effective treatment approaches. The emerging evidence suggests that anti-angiogenic therapy could inhibit angiogenesis and normalize vascular permeability in the tumor microenvironment, which, in turn, would increase immune effector cell infiltration into tumors. Immunotherapy depends on the accumulation and activity of immune effector cells within the tumor microenvironment, and immune responses and vascular normalization seem to be reciprocally regulated. Immunotherapy combined with anti-angiogenic therapy has recently made great progress in the treatment of various types of tumors. However, the effectiveness of the combination treatment in metastatic leiomyosarcoma is undetermined. In this study, we presented a rare case of primary leiomyosarcoma of the bone located in the trochanteric region of the femur, accompanied by multiple distant metastases. After the failure of multi-line therapies including AI regiments as the adjuvant chemotherapy, anlotinib as the first-line therapy, GT regiment as the second-line therapy, and eribulin as the third-line therapy, the patient received combinational therapy with penpulimab plus lenvatinib. The best efficacy for this regimen was a partial response, with a progression-free survival of 8.4 months according to the iRECIST criteria. After a dissociated response was detected without severe toxicities, the patient received local radiotherapy and continued treatment on penpulimab plus lenvatinib and eventually achieved long-term survival benefits with a total of over 60 months of overall survival with good quality of life and ongoing treatment. As our previous retrospective study found that one-third of advanced STS patients could still achieve clinical benefits from rechallenge with multi-targeted tyrosine kinase inhibitors (TKIs), after the failure of previous TKI therapy, this case provided the potential clinical activity of immunotherapy combined with anti-angiogenic TKI rechallenge in metastatic leiomyosarcoma.

Screening of core genes and prediction of ceRNA regulation mechanism of circRNAs in nasopharyngeal carcinoma by bioinformatics analysis.

Background: Nasopharyngeal carcinoma (NPC) represents a highly aggressive malignant tumor. Competing endogenous RNAs (ceRNA) regulation is a common regulatory mechanism in tumors. The ceRNA network links the functions between mRNAs and ncRNAs, thus playing an important regulatory role in diseases. This study screened the potential key genes in NPC and predicted regulatory mechanisms using bioinformatics analysis. Methods: The merged microarray data of three NPC-related mRNA expression microarrays from the Gene Expression Omnibus (GEO) database and the expression data of tumor samples or normal samples from the nasopharynx and tonsil in The Cancer Genome Atlas (TCGA) database were both subjected to differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA). The results from two different databases were intersected with WGCNA results to obtain potential regulatory genes in NPC, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. The hub-gene in candidate genes was discerned through Protein-Protein Interaction (PPI) analysis and its upstream regulatory mechanism was predicted by miRwalk and circbank databases. Results: Totally 68 upregulated genes and 96 downregulated genes in NPC were screened through GEO and TCGA. According to WGCNA, the NPC-related modules were screened from GEO and TCGA analysis results, and the genes in the modules were obtained. After the results of differential analysis and WGCNA were intersected, 74 differentially expressed candidate genes associated with NPC were discerned. Finally, fibronectin 1 (FN1) was identified as a hub-gene in NPC. Prediction of upstream regulatory mechanisms of FN1 suggested that FN1 may be regulated by ceRNA mechanisms involving multiple circRNAs, thereby influencing NPC progression through ceRNA regulation. Conclusion: FN1 is identified as a key regulator in NPC development and is likely to be regulated by numerous circRNA-mediated ceRNA mechanisms.

Identification of the miRNA-mRNA regulatory network associated with radiosensitivity in esophageal cancer based on integrative analysis of the TCGA and GEO data.

BACKGROUND: The current study set out to identify the miRNA-mRNA regulatory networks that influence the radiosensitivity in esophageal cancer based on the The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. METHODS: Firstly, esophageal cancer-related miRNA-seq and mRNA-seq data were retrieved from the TCGA database, and the mRNA dataset of esophageal cancer radiotherapy was downloaded from the GEO database to analyze the differential expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) in radiosensitive and radioresistant samples, followed by the construction of the miRNA-mRNA regulatory network and Gene Ontology and KEGG enrichment analysis. Additionally, a prognostic risk model was constructed, and its accuracy was evaluated by means of receiver operating characteristic analysis. RESULTS: A total of 125 DEmiRNAs and 42 DEmRNAs were closely related to the radiosensitivity in patients with esophageal cancer. Based on 47 miRNA-mRNA interactions, including 21 miRNAs and 21 mRNAs, the miRNA-mRNA regulatory network was constructed. The prognostic risk model based on 2 miRNAs (miR-132-3p and miR-576-5p) and 4 mRNAs (CAND1, ZDHHC23, AHR, and MTMR4) could accurately predict the prognosis of esophageal cancer patients. Finally, it was verified that miR-132-3p/CAND1/ZDHHC23 and miR-576-5p/AHR could affect the radiosensitivity in esophageal cancer. CONCLUSION: Our study demonstrated that miR-132-3p/CAND1/ZDHHC23 and miR-576-5p/AHR were critical molecular pathways related to the radiosensitivity of esophageal cancer.

Nasal-Type Extranodal Natural Killer/T Cell Lymphoma with Meningeal Involvement: A Case Report and Literature Review.

OBJECTIVES: We report a case of a 26-year-old man diagnosed with nasal-type extranodal natural killer/T cell lymphoma (ENKTL) extending beyond the nasal cavity. Complete response was achieved after therapy, followed by rapid metastasis to the meningeal nerve fibres. The overall survival (OS) of the patient was 15 months. To better understand ENKTL with meningeal involvement, we summarized the clinical features of the 10 cases involving meningeal metastasis in ENKTL reported in the English literature. METHODS: The patient was admitted for the ENKTL diagnosis, and positron emission tomography-computed tomography showed the disease stage and response. When central nervous system (CNS) infiltration was suspected, magnetic resonance imaging (MRI) of the brain and spinal cord was performed, as well as cerebrospinal fluid (CSF) analysis with flow cytometric immunophenotyping. RESULTS: MRI of the brain and spinal cord revealed normal results. CSF analysis with flow cytometric immunophenotyping showed NK/T lymphoma cell infiltration. CONCLUSION: Meningeal metastasis of ENKTL is rare; when patients present with nervous system symptoms, CNS metastasis should be considered as a possibility, even in the early stage. The OS of our patient was 15 months, which is the longest survival time reported in the literature, probably due to early diagnosis and comprehensive management, including intrathecal therapy, chemotherapy and radiotherapy of the whole brain and spinal cord.

Contrast-Enhanced MRI Texture Parameters as Potential Prognostic Factors for Primary Central Nervous System Lymphoma Patients Receiving High-Dose Methotrexate-Based Chemotherapy.

Introduction: The purpose of this study was to evaluate the prognostic value of texture features on contrast-enhanced magnetic resonance imaging (MRI) for patients with primary central nervous system lymphoma (PCNSL). Methods: In this retrospective study, fifty-two patients diagnosed with PCNSL were enrolled from October 2010 to March 2017. The texture feature of tumor tissue on the histogram-based matrix (histo-) and the grey-level co-occurrence matrix (GLCM) was retrieved by contrast-enhanced T1-weighted imaging before any antitumor treatment. Receiver operating characteristic curve analyses were performed to obtain their optimal cutoff values, based on which we dichotomized patients into subgroups. The Kaplan-Meier analyses were conducted to compare overall survival (OS) of subgroups, and multivariate Cox regression analyses were used to determine if they could be taken as independent prognostic factors. Results: Ten texture features were extracted from the MR image, including Energy, Entropy, Kurtosis, Skewness on the histogram-based matrix, and Correlation, Contrast, Dissimilarity, Energy, Entropy, and Homogeneity on the grey-level co-occurrence matrix. Three of them (GLCM-Contrast, GLCM-Dissimilarity, and GLCM-Homogeneity) are shown to be significant in relation to overall survival (OS). The multivariate Cox regression analyses suggest that GLCM-Homogeneity could be taken as independent predictors. Conclusions: The texture features of contrast-enhanced magnetic resonance imaging (MRI) could potentially serve as prognostic biomarkers for PCNSL patients.

Three-Dimensional Texture Analysis Based on PET/CT Images to Distinguish Hepatocellular Carcinoma and Hepatic Lymphoma.

Objectives: This study compared the diagnostic ability of image-based parameters with texture parameters in the differentiation of hepatocellular carcinoma (HCC) and hepatic lymphoma (HL) by positron emission tomography-computed tomography (PET/CT). Methods: Patients with pathological diagnosis of HCC and HL were included in this study. Image-based and texture parameters were obtained by manual drawing of region of interest. Receiver operating characteristic (ROC) was used to test the diagnostic capacity of each parameter. Binary logistic regression was used to transform the most discriminative image-based parameters, texture parameters, and the combination of these parameters into three regression models. ROC was used to test the diagnostic capacity of these models. Result: Ninety-nine patients diagnosed with HCC (n = 76) and HL (n = 23, 10 primary HL, 13 secondary HL) by histological examination were included in this study (From 2011 to 2018, West China hospital). According to the AUC and p-value, 2 image-based parameters and five texture parameters were selected. The diagnostic ability of texture-based model was better than that of image-based model, and after combination of those two groups of parameters the diagnostic capacity improved. Conclusion: Texture parameters can differentiate HCC from HL quantitatively and improve the diagnostic ability of image-based parameters.

Endostar, a Modified Endostatin Induces Vascular Normalization to Improve Chemotherapy Efficacy Through Suppression of Src Signaling Pathway.

Pathological angiogenesis can be a significant barrier to effective cancer therapy. Recent evidence suggests that Endostar may induce vascular normalization, thereby improving tumor perfusion and systemic chemotherapy. However, the molecular mechanism by which Endostar makes chemotherapy more effective remains to be fully elucidated. In this study, established 4T1 breast tumor-bearing animals treated with Endostar were evaluated at serial time points for treatment-associated changes in vascular architecture. As a result, Endostar induced a morphologically and functionally normalized vascular network. Combined Endostar and doxorubicin exhibited significant antitumor (34% of control size) and antimetastatic effects (29% of control metastatic nodules) in vivo. Finally, a two-dimensional gel electrophoresis and MALDIQ-TOF MS/MS-based proteomics approach was used to identify differentially expressed proteins involved in vascular normalization during Endostar administration. SRCIN1 was detected as one of the most significantly increased proteins. SRCIN1 is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase, and attenuated Src activation during Endostar treatment was further confirmed by immunoblotting. Collectively, these data provided a molecular basis for vascular normalization, which were associated with the observed synergistic effect in vivo.

Primary pulmonary myoepithelial carcinoma in a young woman: A case report and review of literature.

RATIONALE: Myoepithelial carcinoma mainly occurs in the salivary glands, but myoepithelial carcinoma of the lung is extremely rare neoplasm whose biological behavior and clinical course still remain to be fully elucidated. Although considered as low-grade carcinoma, these tumors have a high rate of recurrence or distant metastasis. PATIENT CONCERNS: To date there are only 11 cases of pulmonary myoepithelial carcinoma reported in the English literature. We report a case of a 24-year-old woman diagnosed with primary pulmonary myoepithelial carcinoma. Informed consent was obtained from the patient. DIAGNOSES: The tumor derived from superior lobe of left lung and exhibited only myoepithelial differentiation without any ductal formation by histopathological and immunohistochemical analysis. INTERVENTIONS: The patient underwent the left superior lobe resection. In addition, we first introduce second-generation sequencing technology as a novel strategy for primary pulmonary myoepithelial carcinoma, and these tumors should be included in the differential diagnosis of thoracic neoplasms. OUTCOMES: The patient was alive with no evidence of disease for up to 12 months. LESSONS: Individualized treatment is the promising clinical strategy for thoracic neoplasms, and the underlying molecular events should be investigated to find the potential therapeutic targets.

A clinical study of 21 patients with hemophagocytic syndrome in 295 cases diagnosed with nasal type, extranodal nature killer/T cell lymphoma.

Nasal type, extranodal nature killer (NK)/T cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS) is a rare and fatal disorder with extremely poor prognosis. To investigate its clinical characteristics and risk factors, we retrospectively analyzed 295 patients with nasal type, extranodal nature killer/T cell lymphoma, of which 21 were diagnosed with hemophagocytic syndrome, with a cumulative incidence of 7.1%. The most frequently clinical characteristics were fever, lymphadenopathy, hepatosplenomegaly, pancytopenia, hyperferritinemia, liver dysfunction, hypertriglyceridemia, hypofibrinogenemia and evaluated lactate dehydrogenase (LDH) level. After a median follow-up of 27 months, the 2-year survival for the 295 patients was 74.6%. Significant difference for 2-year survival was found between patients with and without hemophagocytic syndrome (4.8% vs. 80.0%, P<0.001). After developing hemophagocytic syndrome, all patients survived no more than 3 months, with a median survival of 35 days. Risk factors for NK/T-LAHS were bone marrow (BM) involvement (P = 0.019; relative risk, 13.649; 95% confidence interval (CI): 1.538-121.103), hepatosplenomegaly (P = 0.003; relative risk, 9.616; 95%CI: 2.154-42.918), and elevated LDH level (>314U/L) (P = 0.038; relative risk, 6.293; 95%CI: 1.108-35.735). We conducted a risk model for all 295 patients based on the 3 adverse factors as follows: low risk (233 cases, 79.0%), no factor; intermediate risk (43 cases, 14.6%), one factor; high risk (19 cases, 6.4%), 2 or 3 factors. The probabilities for developing LAHS were 0.9% for low-, 14.0% for intermediate-, and 68.4% for high-risk group. Significant differences in the 3 risk groups were observed (P<0.001).

Five-year analysis from phase 2 trial of "sandwich" chemoradiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma.

The "sandwich" protocol, was first proposed by us and comprised of l-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy, results in 2-year overall survival and progression-free survival rates that surpass traditional therapies for patients with newly diagnosed, stage IE-IIE, nasal type, extranodal natural killer/T-cell lymphoma. The results had been published by cancer. These patients were followed up over a median period of 67 months, for which updates and the results of prognostic factors analyses are presented. The 5-year overall survival and progress-free survival rates were both 64%. The highest rates of death occurred during the first 6 months, and between the second and third year after enrollment. The initial therapeutic response (odds ratio = 5.83; P = 0.001) and B symptoms (odds ratio = 6.13; P = 0.043) were significant prognostic factors for overall survival. However, the international prognostic index was not significant for progress-free survival and overall survival. There were no severe long-term side effects. These results indicate that the "sandwich" protocol may benefit the long-term survival of patients with newly diagnosed stage IE-IIE, nasal type, extranodal natural killer/T-cell lymphoma. However, additional studies with larger samples are required to confirm these results. This study is registered at www.Chictr.org (ChicTR-TNC-09000394).

Can ionization mass spectrometry coupled with ultrasonic scalpel a fine detection method for intraoperative pathological analysis?

Ionization mass spectrometry (IMS) has been reported to detect surgical smoke component and analyze the distribution of phospholipids found in the smoke. Based on the previous studies, electrosurgical and laser knife coupled IMS has been reported to assess pathogenic diagnosis such as tumor malignancy and to guide tumor resection such as real-time surgical margin control. In addition, US operation is a more closed space for smoke detection than the others. Thus, in this study we speculate that ultrasonic scalpel (US) generated smoke could also be detected, which might has a better detection effect and the assessment would has a fine application prospect.

Management of rectal inflammatory myofibroblastic tumor recurrence.

Inflammatory myofibroblastic tumor (IMT) is an uncommon mesenchymal neoplasm of intermediate malignant potential. It may occur in various anatomic locations, but rarely in the rectum. This is a case discussion of a 36-year-old male patient with IMT of the rectum. After the patient underwent radical surgery, recurrence was seen after 18 months. Because the tumor was very close to the surrounding tissue, palliative tumor resection was performed followed by concurrent chemo-radiation and non-steroidal anti-inflammatory drugs (NSAID). After 2-year follow-up, the patient has no evidence of recurrence or metastasis. Surgical resection is very important for patient with rectal IMT, even in relapse cases. And adjuvant chemoradiotherapy and NSAID are in favor of the incompletely resected tumors as our case. But perhaps, the adjuvant treatments could be helpful after radical resection of rectal tumor.

Testing for hepatitis B infection in prospective chemotherapy patients: a retrospective study.

AIM: To estimate hepatitis B virus (HBV) infection testing rate in cancer patients before chemotherapy with a focus on HBV reactivation. METHODS: A retrospective study was conducted from January 1, 2009 to June 30, 2010. Inclusion required that patients be naïve to cancer chemotherapy but have indications for it. Patients who did not receive chemotherapy for any reason were excluded. Important clinical information, such as the levels of HBV DNA and serological markers were collected. HBV reactivation was defined as an increase in serum HBV DNA to > 1 log higher than that of the pre-exacerbation baseline, or serum HBV DNA conversion from negative to positive. HBV DNA levels > 1000 copies/mL were defined as HBV DNA positive. The χ² or Fisher's exact test was used for analysis of categorized data. Multiple logistic regression analysis was used to estimate the odd ratio and 95%CI of the HBV screening rate. RESULTS: Of 6646 patients, 5616 (84.5%) received chemotherapy. Only 17.1% of the cancer patients received pre-chemotherapy HBV testing (43.2% for hematological malignancies and 14.9% for solid tumors). Patients who had received rituximab therapy, had elevated aminotransferase levels, or had hematological malignancies were more likely to receive HBV testing. The prevalence of hepatitis B surface antigen (HBsAg) positivity was 13.4%. HBV reactivation (appearance of HBV DNA or an increase in HBV DNA levels by 1 log10 was observed in 33.1% (53/160) of the patients after chemotherapy. Among patients without prophylactic antiviral therapy, the reactivation rate was 43.9% (43/98) in the solid tumor group. Two reactivation cases occurred in patients who were HBsAg negative, but positive for hepatitis B core antibody. HBV reactivation was more likely to occur in patients with lymphoma, high levels of HBV DNA, or hepatitis B e antigen, and in men. CONCLUSION: Less than 20% of patients received HBV testing before chemotherapy. HBV reactivation would have occurred in about 50% of infected patients with solid tumors without antiviral prophylaxis.