Mean platelet volume/platelet count ratio in combination with tumor markers in colorectal cancer: a retrospective clinical study.

BACKGROUND: Mean platelet volume (MPV) is a marker of platelet activation, which is usually negatively correlated with platelet count (PC). The ratio of MPV to PC (MPV/PC) has an essential role in the diagnosis of multiple malignancies. However, only a few studies investigated the value of MPV/PC in colorectal cancer (CRC) and the combination of MPV/PC with tumor markers in CRC. This retrospective clinical study aimed to evaluate the diagnostic value of MPV/PC and tumor markers (CA72-4, CA125, CA199) used alone or in combination in CRC. METHODS: 200 patients with CRC and 317 patients with colorectal benign polypus pathologically diagnosed during 2019/01/04 to 2022/06/30 were included. Hematological and pathological parameters of the above patients were collected, data were analyzed with Student's t-test, one-way ANOVA or Kruskal-Wallis H test and receiver operating characteristic (ROC) curve, and ROC curve was used to evaluate the diagnostic value of tumor markers and MPV/PC used alone or in combination in CRC. RESULTS: The MPV/PC in CRC group was significantly lower than the control group (P < 0.0001). Among the three tumor markers, higher CA125 was correlated with distant metastasis and lower differentiation (P < 0.05), increased CA72-4 indicated positive nerve invasion (P = 0.0174), and elevated CA199 was associated with lymphatic metastasis and positive vascular invasion (P < 0.05). For subgroups regarding tumor anatomical location, both CA125 and CA199 were higher in colon cancer group than rectum cancer group (P = 0.0322, P = 0.0094). MPV/PC was associated with tumor infiltration, regional lymph node metastasis, differentiation and nerve invasion (P < 0.05) and the combination of MPV/PC with the three tumor markers produced a larger AUC with higher sensitivity, specificity and Yuden index than MPV/PC or the three tumor markers used alone to distinguish between CRC and colorectal polyps. CONCLUSION: Preoperative MPV/PC in peripheral blood of patients with CRC was lower than the control group. Meanwhile, the combined detection of tumor markers with MPV/PC can improve the diagnostic value of CRC, revealing the potential of MPV/PC as a promising screening tool in CRC early diagnosis.

Expressions of EZH2 and NOTCH3 pathway in osteosarcoma and their roles in osteosarcoma stem cells.

Osteosarcoma (OS) is the most common malignant bone tumour; however, the underlying mechanisms are mainly unknown. Enhancer of zeste homologue 2 (EZH2) and NOTCH pathway are important molecular signals related to carcinogenesis and tumour progression, but they are not fully understand in OS. Enhancer of zeste homologue 2, Notch3, HES1, and Nanog were detected on OS samples and statistically analysed. Expressions of these genes were investigate, and stem-like phenotype was verified in OS cells. This study found that higher EZH2 expression, Notch3 pathway, or Nanog were associated with tumour relapse and metastasis and a significantly shorter survival time. Moreover, the Notch3 pathway was activated in osteosarcoma stem cells. Enhancer of zeste homologue 2 overexpression could activate the Notch3 pathway and increase HES1 expression, leading to upregulated stem cell-related gene expression and self-renewal of OS cells. Our study demonstrates that EZH2, Notch3, and Nanog are important prognostic factors. Enhancer of zeste homologue 2 could maintain the self-renewal of OS cells, where the Notch3 pathway activation may be involved.

Pathologic complete response to preoperative immunotherapy in a lung adenocarcinoma patient with bone metastasis: A case report.

Anti-programmed cell death 1 (PD-1) and its ligand (PD-L1) has emerged as a novel immunotherapy for non-small cell lung cancer (NSCLC). However, the proportion of patients who may benefit from immunotherapy is limited and the factors sensitive or resistant to immunotherapy are not completely clear. Therefore, to identify reliable biomarkers as predictors of clinical response and resistance to anti-PD-1/PD-L1 therapies have become increasingly important. Here, we report a case of a patient with bone metastatic NSCLC, who achieved a pathologic complete response after preoperative pembrolizumab treatment. Postoperative pathological examination found no viable cancer cells in the resected pulmonary nodules and lymph nodes. Several high-frequency DNA damage response and repair (DDR) gene mutations including two germline mutations were identified in the primary lesion. Moreover, high PD-L1 expression, Kirsten rat sarcoma viral oncogene homolog (KRAS) combined with tumor protein 53 (TP53) mutations without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) driver alterations, high infiltration level of CD8-positive cells and M1 macrophages were observed, which were favorable characteristics for immunotherapy. We explored the possible factors related to an excellent response to immune checkpoint inhibitor in this patient and determined that preoperative use of anti-PD-1 therapy might apply to late-stage lung adenocarcinoma patients with multidimensional advantageous biomarkers for treatment with immune checkpoint inhibitors (ICIs). KEY POINTS: We characterized the genomic features and immune microenvironment signature of a lung adenocarcinoma in a patient with bone metastasis who achieved pathologic complete response after pembrolizumab treatment. To evaluate multidimensional advantageous biomarkers for immunotherapy.

Identification of Different Form Tim-3 Proteins by a Unique Set of Tim-3 Monoclonal Antibodies.

T-cell immunoglobulin and mucin domain-3 (Tim-3) has been suggested to be a critical immune checkpoint target for cancer immunotherapy. However, limited progress with Tim-3 immunotherapy has been achieved over the last decade due to the lack of specific Tim-3 monoclonal antibodies. In this study, we have successfully developed a unique set of Tim-3 antibodies that are able to detect different molecular weights (by Western blot mobility) of Tim-3 proteins ectopically expressed in the same CHO cells. Some of the antibody clones detect only 33 or 55 kDa bands, the rest can recognize both 33 and 55 kDa bands on polyacrylamide gel electrophoresis gel. Antibody clones with 55 kDa specificity uniquely bind to the membrane form of Tim-3 on macrophage, which colocalizes with the CD68, and could be used as a specific marker for tumor-associated macrophage, whereas other clones showed cytoplasmic staining in tumor cells. The membrane form of Tim-3 on tumor-associated macrophages may bear significant roles for clinical application of Tim-3, but less likely for cytoplasmic one. The availability of this unique set of antibodies will be critical for an ultimate understanding of Tim-3 function in tumor microenvironment and potential clinical applications.

Case report: metastases from thyroid and nasopharyngeal carcinomas in the same lymph node following chemotherapy for mantle cell lymphoma.

We report a case of metastatic papillary thyroid carcinoma and undifferentiated nonkeratinizing nasopharyngeal carcinoma to the same cervical lymph node following chemotherapy for mantle cell lymphoma. Total thyroidectomy, right cervical nodal dissection, radioactive iodine-131 therapy and radiotherapy to the nasopharynx and the neck resulted in remission of both tumors. No recurrence was noted in follow-up for 48 months.

[Pulmonary epithelioid hemangioendothelioma: a clinicopathological analysis].

OBJECTIVE: To report 3 cases of pulmonary epithelioid haemangioendothelioma (PEH) and therefore to improve the understanding of this tumor. METHODS: The clinical pathological features of 3 cases of PEH were described and related literatures were reviewed. RESULTS: The etiology of this rare disease remained unknown. Symptoms were scanty and usually mild. Chest radiograph or computed tomography usually revealed multiple bilateral pulmonary nodules. Histologically, crown-like clusters of epithelioid tumor cells or spindle cells were filled in the alveoli at the periphery of the tumor nodules, while the central part of the nodules contained myxoid to hyaline matrix. Tumor cells generally lacked pleomorphism, mitotic activity and necrosis. They were immunohistochemically positive for CD(31) and CD(34). CK staining was positive in some cases. There was no effective treatment for this disease and its prognosis was unpredictable. CONCLUSIONS: PEH is a low grade malignancy and represents a distinct clinical pathological entity. It is rare and often misdiagnosed as other pulmonary diseases.

Extraction of prostatic lumina and automated recognition for prostatic calculus image using PCA-SVM.

Identification of prostatic calculi is an important basis for determining the tissue origin. Computation-assistant diagnosis of prostatic calculi may have promising potential but is currently still less studied. We studied the extraction of prostatic lumina and automated recognition for calculus images. Extraction of lumina from prostate histology images was based on local entropy and Otsu threshold recognition using PCA-SVM and based on the texture features of prostatic calculus. The SVM classifier showed an average time 0.1432 second, an average training accuracy of 100%, an average test accuracy of 93.12%, a sensitivity of 87.74%, and a specificity of 94.82%. We concluded that the algorithm, based on texture features and PCA-SVM, can recognize the concentric structure and visualized features easily. Therefore, this method is effective for the automated recognition of prostatic calculi.

Primary malignant bone neoplasm: a case report of dedifferentiated chondrosarcoma in the rib and review of the literature.

Dedifferentiated chondrosarcoma (DDCS) is a rare but highly malignant primary bone neoplasm, which is resistant to radiotherapy and chemotherapy. There remains uncertainly as to the best treatment of this disease and how to improve its prognosis. In this paper we reported a case of DDCS and reviewed the related literatures in order to provide references to throw a light on the histogenesis, diagnosis and therapy of this disease.

[Pathological and ultramicrostructural changes of tissues in a patient with severe acute respiratory syndrome].

OBJECTIVE: To study the morphological, ultramicrostructural and pathological changes of tissues from a patient with severe acute respiratory syndrome (SARS). METHODS: One autopsy case of diagnosed SARS was investigated. Lung puncture was performed immediately after the patient died, and the autopsy was done after 12 h. The specimens from lymph nodes, spleen, small intestine, colon and bone marrow were studied by immunohistochemical technique. The antibodies used included CD20, CD45RO (UCHL-1), CD4, CD8, CD68 and CD34. RESULTS: The principal lesions of the SARS case consisted of acute lobular intrastitial pneumonia, hyaloid membranes of pulmonic alveoli and hyperplasia and shedding of alveolar epithelium of. Virus-like inclusions occasionally contained cytoplasm of the alveolar epithelium, which were positive by histochemical staining. The adjacent blood-vessels were changed by hyperplasia and enlargement. The structures of lymph nodes and spleen were damaged with lymph follicles depletion and splenic nodules atrophy. The specific changes included reduction of lymphocytes and hyperplasia of histiocytes, depletion of the follicles of small intestine and colon wall, decreased hyperplasia of the bone marrow and increased number of the megakaryocyte. Meanwhile, in the immunohistochemical study, CD(20)(+) B cells were fully expressed in lymph nodes and spleen, and the CD45RO (UCHL-1)(+) T cells were scatteredly expressed. The number of CD4(+) help T cell was markedly decreased, while the number of CD8+ poisonal T cells increased, and the ratio of the former and latter was no more than 0.5. Under the electronic microscopy observation, virus-like particles with 80 - 160 nm diameter and halo or garland envelope were found in mononuclear macrophage and cytoplasm of alveolar epithelium. CONCLUSION: The specific lesions of SARS consist of lobular intrastitial pneumonia with the formation of hyaline membranes of lung, haemorrhage, necrosis, inflammation of blood vessels and the damages of extralung lymphohemopioetic system. The damages were very similar to the pathological features of tissues infected by human immunodeficiency virus, in which numbers of T cells decreased and CD(4)(+) T cell/CD(8)(+) T cell ratio was no more than 0.5. According to the virus-like particles found in lung of the SARS case, it is considered that these virus-like particles may be a new kind of coronavirus which caused the "atypical pneumonia".