1.Comparative study of orthopaedic robot-assisted minimally invasive surgery and open surgery for limb osteoid osteoma.
Junwei FENG ; Weimin LIANG ; Yue WANG ; Zhi TANG ; MuFuSha A ; Baoxiu XU ; Niezhenghao HE ; Peng HAO
Chinese Journal of Reparative and Reconstructive Surgery 2024;38(1):40-45
OBJECTIVE:
To compare the accuracy and effectiveness of orthopaedic robot-assisted minimally invasive surgery versus open surgery for limb osteoid osteoma.
METHODS:
A clinical data of 36 patients with limb osteoid osteomas admitted between June 2016 and June 2023 was retrospectively analyzed. Among them, 16 patients underwent orthopaedic robot-assisted minimally invasive surgery (robot-assisted surgery group), and 20 patients underwent tumor resection after lotcated by C-arm X-ray fluoroscopy (open surgery group). There was no significant difference between the two groups in the gender, age, lesion site, tumor nidus diameter, and preoperative pain visual analogue scale (VAS) scores ( P>0.05). The operation time, lesion resection time, intraoperative blood loss, intraoperative fluoroscopy frequency, lesion resection accuracy, and postoperative analgesic use frequency were recorded and compared between the two groups. The VAS scores for pain severity were compared preoperatively and at 3 days and 3 months postoperatively.
RESULTS:
Compared with the open surgery group, the robot-assisted surgery group had a longer operation time, less intraoperative blood loss, less fluoroscopy frequency, less postoperative analgesic use frequency, and higher lesion resection accuracy ( P<0.05). There was no significant difference in lesion resection time ( P>0.05). All patients were followed up after surgery, with a follow-up period of 3-24 months (median, 12 months) in the two groups. No postoperative complication such as wound infection or fracture occurred in either group during follow-up. No tumor recurrence was observed during follow-up. The VAS scores significantly improved in both groups at 3 days and 3 months after surgery when compared with preoperative value ( P<0.05). The VAS score at 3 days after surgery was significantly lower in robot-assisted surgery group than that in open surgery group ( P<0.05). However, there was no significant difference in VAS scores at 3 months between the two groups ( P>0.05).
CONCLUSION
Compared with open surgery, robot-assisted resection of limb osteoid osteomas has longer operation time, but the accuracy of lesion resection improve, intraoperative blood loss reduce, and early postoperative pain is lighter. It has the advantages of precision and minimally invasive surgery.
Humans
;
Robotics
;
Osteoma, Osteoid/surgery*
;
Orthopedics
;
Blood Loss, Surgical
;
Retrospective Studies
;
Neoplasm Recurrence, Local
;
Minimally Invasive Surgical Procedures
;
Bone Neoplasms/surgery*
;
Analgesics
;
Treatment Outcome
2.B7-H3 confers stemness characteristics to gastric cancer cells by promoting glutathione metabolism through AKT/pAKT/Nrf2 pathway.
Lu XIA ; Yuqi CHEN ; Juntao LI ; Jiayu WANG ; Kanger SHEN ; Anjing ZHAO ; Haiyan JIN ; Guangbo ZHANG ; Qinhua XI ; Suhua XIA ; Tongguo SHI ; Rui LI
Chinese Medical Journal 2023;136(16):1977-1989
BACKGROUND:
Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism.
METHODS:
GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis.
RESULTS:
B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02).
CONCLUSIONS
B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
Humans
;
Cell Line, Tumor
;
Neoplasm Recurrence, Local
;
NF-E2-Related Factor 2/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Signal Transduction
;
Stomach Neoplasms
3.Clinical Anslysis of Primary Adrenal NK/T-Cell Lymphoma.
Xin-Yue JI ; Da-Peng SHENG ; Yu-Qiong YANG ; Yuan-Feng WEI ; Xi HUANG ; Qiong LIU ; Dan-Ning YU ; Yu-Xin GUO ; He-Sheng HE
Journal of Experimental Hematology 2023;31(2):396-402
OBJECTIVE:
To investigate the clinical characteristics, diagnosis, and treatment of one patient with primary adrenal natural killer/T-cell lymphoma (PANKTCL), and to strengthen the understanding of this rare type of lymphoma.
METHODS:
The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in our hospital were retrospectively analyzed.
RESULTS:
Combined with pathology, imaging, bone marrow examination, etc, the patient was diagnosed with PANKTCL (CA stage, stage II; PINK-E score 3, high-risk group). Six cycles of "P-GemOx+VP-16" regimen(gemcitabine 1 g/m2 d1 + oxaliplatin 100 mg/m2 d 1 + etoposide 60 mg/m2 d 2-4 + polyethylene glycol conjugated asparaginase 3 750 IU d 5) was performed, and complete response was assessed in 4 cycles. Maintenance therapy with sintilimab was administered after the completion of chemotherapy. Eight months after the complete response, the patient experienced disease recurrence and underwent a total of four courses of chemotherapy, during which hemophagocytic syndrome occurred. The patient died of disease progression 1 month later.
CONCLUSION
PANKTCL is rare, relapses easily, and has a worse prognosis. The choice of the "P-GemOx+VP-16" regimen combined with sintilimab help to improve the survival prognosis of patient with non-upper aerodigestive tract natural killer /T-cell lymphoma.
Humans
;
Treatment Outcome
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Retrospective Studies
;
Etoposide
;
Neoplasm Recurrence, Local/drug therapy*
;
Asparaginase
;
Deoxycytidine
;
Lymphoma, T-Cell, Peripheral/drug therapy*
;
Lymphoma, Extranodal NK-T-Cell/therapy*
;
Oxaliplatin/therapeutic use*
4.Effects of C10orf10 on growth and prognosis of glioma under hypoxia.
Yuanbing CHEN ; Miao TANG ; Hui LI ; Jun HUANG
Journal of Central South University(Medical Sciences) 2023;48(4):499-507
OBJECTIVES:
Glioma is the most common malignant tumor in the central nervous system, and the hypoxic microenvironment is prevalent in solid tumors. This study aims to investigate the up-regulation of genes under the condition of hypoxia and their roles in glioma growth, as well as their impact on glioma prognosis.
METHODS:
The hypoxia-related dataset with glioma was screened in the Gene Expression Omnibus database (GEO), and the differentially expressed genes were analyzed between hypoxia and normoxia through bioinformatics, and chromosome 10 open reading frame 10 (C10orf10) was verified and screened in hypoxia-treated cells through real-time PCR and Western blotting. The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets were downloaded to analyze the mRNA expression of C10orf10 in different grades of glioma and its impact on prognosis. The glioma specimens and follow-up data of 68 gliomas who underwent surgical treatment in Xiangya Hospital of Central South University from March 2017 to January 2021 were collected, and real-time PCR was used to detect the mRNA expression of C10orf10 in different grades of glioma, and the Kaplan-Meier method was used to analyze the relationship between the expression C10orf10 and prognosis. The glioma cells, which could interfere the expression of C10orf10, were constructed, and the effect of C10orf10 on the proliferation of glioma cells was evaluated by cell counting kit-8 (CCK-8) and colony formation assays.
RESULTS:
Compared with the condition of normoxia, the expression levels of C10orf10 mRNA and protein were significantly up-regulated in glioma cells under hypoxia (P<0.001), and the mRNA expression level of C10orf10 in glioma tissues was up-regulated with the increase of WHO grade in glioma (P<0.001). Based on Kaplan-Meier survival analysis, the higher the mRNA expression level of C10orf10 was, the shorter the survival time of the patient was (P<0.05). And the expression of C10orf10 mRNA was higher in recurrent gliomas than that in primary gliomas in the CGGA database (P<0.001). Knockdown of C10orf10 could significantly inhibit the growth of glioma cells both under hypoxia and normoxia (both P<0.001).
CONCLUSIONS
The expression level of C10orf10 can promote the proliferation and prognosis of glioma, which is expected to become a prognostic marker and therapeutic target for glioma.
Humans
;
Central Nervous System
;
Glioma/genetics*
;
Hypoxia
;
Neoplasm Recurrence, Local
;
Prognosis
;
Tumor Microenvironment
5.Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology.
Zhihang HU ; Modan YANG ; Hao CHEN ; Chiyu HE ; Zuyuan LIN ; Xinyu YANG ; Huigang LI ; Wei SHEN ; Di LU ; Xiao XU
Journal of Zhejiang University. Science. B 2023;24(5):387-396
Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer. In addition to the common mechanisms underlying tumor recurrence, another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis. Transplant oncology is an emerging field that addresses oncological challenges in transplantation. In this context, a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients. Double-negative T cells (DNTs) are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor (TCR) type. Among them, TCRαβ+ DNTs are considered to induce immune suppression in immune-mediated diseases, while TCRγδ+ DNTs are widely recognized as tumor killers. As a composite cell therapy, healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host. In this work, we summarized the biological characteristics and functions of DNTs in oncology, immunology, and transplantation. Based on the multiple roles of DNTs, we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy (ACT).
Humans
;
T-Lymphocytes
;
Immunotherapy, Adoptive
;
Neoplasm Recurrence, Local
;
Transplantation, Homologous
;
Cell- and Tissue-Based Therapy
6.Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant.
Yong Qiang ZHAO ; Yan Zhi SONG ; Zhi Hui LI ; Fan YANG ; Teng XU ; Fei Fei LI ; Dong Fang YANG ; Tong WU
Chinese Journal of Hematology 2023;44(6):465-471
Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.
Humans
;
Adult
;
Retrospective Studies
;
Neoplasm Recurrence, Local
;
Hematologic Neoplasms/therapy*
;
Busulfan/therapeutic use*
;
Graft vs Host Disease/prevention & control*
;
Chronic Disease
;
Unrelated Donors
;
Hematopoietic Stem Cell Transplantation
;
Transplantation, Homologous
;
Transplantation Conditioning
8.Thoracic SMARCA4-deficient undifferentiated tumor-pathological diagnosis and combined immune checkpoint inhibitor treatment.
Yan XIONG ; Bo ZHANG ; Li Gong NIE ; Shi Kai WU ; Hu ZHAO ; Dong LI ; Ji Ting DI
Journal of Peking University(Health Sciences) 2023;55(2):351-356
We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.
Humans
;
Immune Checkpoint Inhibitors
;
Neoplasm Recurrence, Local
;
Lung Neoplasms/genetics*
;
Thoracic Neoplasms/pathology*
;
Adenocarcinoma
;
DNA Helicases
;
Nuclear Proteins
;
Transcription Factors
9.Application of supraclavicular fasciocutaneous island flap for reconstruction after removal of tumors in parotid and auricle area.
Yu Chao LUO ; Qing Lai TANG ; Xin Ming YANG ; Zi An XIAO ; Gang Cai ZHU ; Dan Hui YIN ; Qian YANG ; Pei Ying HUANG ; Shi Ying ZENG ; Shi Sheng LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(5):486-491
Objective: To evaluate the efficacy of supraclavicular fasciocutaneous island flap (SIF) for repairing the defect of parotid or auricle regions after tumor resection. Methods: From February 2019 to June 2021, 12 patients (11 males and 1 female, aged 54-77 years old), of whom 4 with parotid adenoid cystic carcinoma and 8 with auricular basal cell carcinoma underwent reconstruction surgery for postoperative defects in the parotid gland area and auricular area with SIF in the Department of Otorhinolaryngology Head and Neck Surgery, the Second Xiangya Hospital of Central South University and their clinical data were retrospectively analyzed. Size of the SIF, time for harvesting SIF, neck lymph node dissection and postoperative complications were recorded. Results: The flap areas were (6-9) cm × (8-13) cm, and the harvesting time for SIF ranged from 40 to 80 min, averaging 51.7 min. The donor sites were directly closed. All patients underwent ipsilateral levels Ⅰ-Ⅲ neck dissection, with 4 cases undergoing additional level Ⅳ neck dissection and 2 cases undergoing level Ⅳ-Ⅴ neck dissection. Of the 12 SIF, 10 were completely survival and 2 had flap arterial crisis with partial flap necrosis, in addition, 1 had donor site wound dehiscence. With follow-up of 10-42 months, there were no tumor recurrences in 10 patients, 1 patient was lost to follow-up at 10 months postoperatively, and 1 patient experienced local tumor recurrence at 11 months after surgery and died 15 months later. Conclusion: SIF is an easily harvested flap with good skin features matching the skin in parotid and auricle regions and less damage to donor site, and this flap has no need for microvascular anastomosis technique. SIF is feasible and effective for repairing defects in parotid and auricle area.
Male
;
Humans
;
Female
;
Middle Aged
;
Aged
;
Plastic Surgery Procedures
;
Parotid Gland/surgery*
;
Retrospective Studies
;
Neoplasm Recurrence, Local
;
Surgical Flaps/blood supply*
;
Skin Transplantation/methods*
;
Postoperative Complications
;
Treatment Outcome

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