OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Background: Vitamin B12 is one of the common drugs used by physicians to treat peripheral neuropathy (PN), although many patients have a good response, however, overdose and toxicity aggravate the condition and worsen the patient’s symptoms. The purpose of this paper is to highlight association between Vitamin B12 toxicity and deterioration of PN symptoms. Case Summary: An elder Sudanese man with acute onset of sensory PN, the patient’s symptoms started by tingling sensations and paresthesia affecting both hands and feet. After patient received cobalamin (vitamin B 12) prescribed by his doctor, the patient symptoms were markedly aggravated and his condition worsened to extend that impaired the normal patient ordinary work. No symptoms related to motor system. Other possible etiologies were studied and excluded. Investigations of his condition revealed blood level of B12 was 1900 pg/mL, the patient condition improved dramatically with discontinuation of the drug. Conclusion Cobalamin toxicity aggravate sensory PN symptoms. Clinicians are advised to adjust the dose and check Cobalamin level before and during treatment to avoid its toxicity.
Peripheral Nervous System Diseases ; Vitamin B 12

OBJECTIVE: To investigate the clinical effect of electroacupuncture (EA) in preventing chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Fifty-two patients with breast cancer in the regimen of taxane-assisted/neoadjuvant chemotherapy, were randomly divided into an EA group (26 cases, 3 cases dropped out) and a usual care (UC) group (26 cases, 1 case dropped out). In the UC group, on the basis of standard chemotherapy regimen, the routine nursing was administered. In the EA group, on the intervention as the UC group, EA was added, the acupoints included Yintang (GV 24⁺), Baxie (EX-UE 9, the second one), Waiguan (TE 5), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), Yinlingquan (SP 9), Sanyinjiao (SP 6), Taixi (KI 3), Taichong (LR 3), Xuanzhong (GB 39) and Bafeng (EX-LE 10, the fourth one). Electric stimulation was attached to Taichong (LR 3) and Sanyinjiao (SP 6) on the same side, with disperse-dense wave and the frequency of 2 Hz/10 Hz, for 30 min. EA started one day before the first cycle of chemotherapy, twice weekly in the first two weeks and once weekly in the rest weeks of chemotherapy. The duration of the intervention with EA was 12 weeks. The incidence of CIPN was compared in week 24 of the trial between the two groups. At the baseline and in week 12 and 24 of the trial, the score of EORTC QLQ-CIPN20 (European Organization for Research and Treatment of Cancer on chemotherapy-induced peripheral nerve toxicity quality of life questionnaire 20), the score of TCM syndrome scale and the score of EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer on quality of life scale) were observed in the two groups. At the baseline and in week 12 of the trial, the sensory nerve conduction velocity (SCV) and the motor nerve conduction velocity (MCV) was detected. RESULTS: In week 24 of the trial, the incidence of CIPN was 17.4% (4/23) in the EA group, lower than that (72.0%, 18/25) in the UC group (P<0.001). The incidence of high-grade CIPN was 0% (0/23) in the EA group, lower than that (28.0%, 7/25) in the UC group (P<0.05). In week 12 and 24 of the trial, the scores for the sensory nerve symptom of EORTC QLQ-CIPN20 and the total scores were higher when compared with the baseline in the UC group (P<0.001, P<0.05, P<0.01). In week 24 of the trial, the score for the sensory nerve symptom of EORTC QLQ-CIPN20 in the EA group was lower than that of the UC group (P<0.05). In week 12 of the trial, SCV of the right superficial peroneal nerve was reduced when compared with the baseline in the UC group (P<0.05), and SCV of the left median nerve and the right superficial peroneal nerve was higher in the EA group when compared with the UC group (P<0.05, P<0.01). In week 12 and 24 of the trial, the scores for the secondary symptoms of TCM scale were decreased in the EA group compared with the baseline (P<0.05), and the scores for the primary and secondary symptoms, as well as the total scores of TCM scale were all higher than those of the baseline in the UC group (P<0.01, P<0.001, P<0.05). In week 12 of the trial, the scores for the primary and secondary symptoms, as well as the total score of TCM scale in the EA group were lower than those of the UC group (P<0.05, P<0.01). In week 24 of the trial, the score for the secondary symptoms and the total score of TCM scale in the EA group were lower than those of the UC group (P<0.05). In week 12 of the trial, the scores for fatigue, pain, nausea and vomiting in EORTC QLQ-C30 were increased in comparison with the baseline in the UC group (P<0.05, P<0.01); in week 24 of the trial, the score of the general health in EORTC QLQ-C30 was elevated when compared with the baseline in the EA group (P<0.001), and the scores for nausea and vomiting, loss of appetite were decreased in comparison with the baseline (P<0.01). In week 12 of the trial, the score of the general health in EORTC QLQ-C30 in the EA group was higher compared with the UC group (P<0.01), and the scores for pain, nausea and vomiting were lower (P<0.01, P<0.05). In week 24 of the trial, the score of the general health in EORTC QLQ-C30 was higher in the EA group compared with the UC group (P<0.001), and the score for loss of appetite was lower (P<0.05). CONCLUSION Electroacupuncture reduces the incidence and severity of CIPN, ameliorates nerve conduction velocity and improves the quality of life of the patients.
Humans ; Electroacupuncture ; Female ; Peripheral Nervous System Diseases/prevention & control* ; Middle Aged ; Adult ; Breast Neoplasms/therapy* ; Antineoplastic Agents/adverse effects* ; Aged

OBJECTIVES: To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN. METHODS: The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups. RESULTS: A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05). CONCLUSIONS There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.
Child ; Humans ; Antineoplastic Agents, Phytogenic/adverse effects* ; Cohort Studies ; Peripheral Nervous System Diseases/diagnosis* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Vincristine/adverse effects* ; Infant ; Child, Preschool ; Adolescent

Objective: To study the clinicopathological characteristics, and further understand primary central nervous system T-cell lymphoma (PCNSTCL) in children and adolescents. Methods: Five cases of PCNSTCL in children and adolescents were collected from December 2016 to December 2021 at the First Affiliated Hospital of Zhengzhou University. The clinicopathological characteristics, immunophenotypic, and molecular pathologic features were analyzed, and relevant literatures reviewed. Results: There were two male and three female patients with a median age of 14 years (range 11 to 18 years). There were two peripheral T-cell lymphomas, not otherwise specified, two anaplastic large cell lymphoma, ALK-positive and one NK/T cell lymphoma. Pathologically, the tumor cells showed a variable histomorphologic spectrum, including small, medium and large cells with diffuse growth pattern and perivascular accentuation. Immunohistochemistry and in situ hybridization showed CD3 expression in four cases, and CD3 was lost in one case. CD5 expression was lost in four cases and retained in one case. ALK and CD30 were expressed in two cases. One tumor expressed CD56 and Epstein-Barr virus-encoded RNA. All cases showed a cytotoxic phenotype with expression of TIA1 and granzyme B. Three cases had a high Ki-67 index (>50%). T-cell receptor (TCR) gene rearrangement was clonal in two cases. Conclusions: PCNSTCL is rare, especially in children and adolescents. The morphology of PCNSTCL is diverse. Immunohistochemistry and TCR gene rearrangement play important roles in the diagnosis.
Female ; Humans ; Male ; Central Nervous System/pathology* ; Central Nervous System Neoplasms/pathology* ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Lymphoma, T-Cell/pathology* ; Lymphoma, T-Cell, Peripheral/genetics* ; Receptor Protein-Tyrosine Kinases/genetics* ; Receptors, Antigen, T-Cell ; Child ; Adolescent

This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.
Humans ; Blood Glucose ; Diabetic Neuropathies/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Glycated Hemoglobin ; Hypesthesia/drug therapy* ; Multicenter Studies as Topic ; Pain/etiology* ; Treatment Outcome ; Peripheral Nervous System Diseases/etiology*

OBJECTIVE: To construct and validate a nomogram for predicting the risk of secondary peripheral neuropathy in patients with advanced lung cancer. METHODS: The sociodemographic and clinical data of 335 patients with advanced lung cancer admitted to Department of Respiratory, the First Affiliated Hospital of Zhejiang University School of Medicine from May 2020 to May 2021 were retrospectively collected. Pearson correlation analysis, univariate and multivariate logistic regression analyses were used to identify the risk factors of secondary peripheral neuropathy in patients with advanced lung cancer. A nomogram was constructed according to the contribution of each risk factor to secondary peripheral neuropathy, and the receiver operating characteristic (ROC) curve, Calibration curve and clinical decision curve were used to evaluate differentiation, calibration, and the clinical utility of the model. The nomogram was further validated with data from 64 patients with advanced lung cancer admitted between June 2021 and August 2021. RESULTS: The incidences of secondary peripheral neuropathy in two series of patients were 34.93% (117/335) and 40.63% (26/64), respectively. The results showed that drinking history ( OR=3.650, 95% CI: 1.523-8.746), comorbid diabetes ( OR=3.753, 95% CI: 1.396-10.086), chemotherapy ( OR=2.887, 95% CI: 1.046-7.970), targeted therapy ( OR=8.671, 95% CI: 4.107-18.306), immunotherapy ( OR=2.603, 95% CI: 1.337-5.065) and abnormal liver and kidney function ( OR=12.409, 95% CI: 4.739-32.489) were independent risk factors for secondary peripheral neuropathy (all P<0.05). A nomogram was constructed based on the above risk factors. The area under the ROC curve (AUC) of the nomogram for predicting the secondary peripheral neuropathy was 0.913 (95% CI: 0.882-0.944); and sensitivity, specificity, positive and negative predictive values were 85.47%, 81.65%, 71.43% and 91.28%, respectively. The Calibration curve and clinical decision curve showed good calibration and clinical utility. External validation results showed that the AUC was 0.764 (95% CI: 0.638-0.869); and sensitivity, specificity, positive and negative predictive values were 79.28%, 85.79%, 73.25% and 85.82%, respectively. CONCLUSIONS Advanced lung cancer patients have a high risk of secondary peripheral neuropathy after anticancer therapy. Drinking history, comorbid diabetes, chemotherapy, targeted therapy, immunotherapy, abnormal liver and kidney function are independent risk factors. The nomogram prediction model constructed in the study is effective and may be used for the risk assessment of secondary peripheral neuropathy in patients with advanced lung cancer.
Humans ; Nomograms ; Retrospective Studies ; Peripheral Nervous System Diseases/etiology* ; Risk Factors ; Lung Neoplasms/complications*

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical problem and challenging for oncologists. CIPN is often a persistent adverse consequence of certain chemotherapeutic agents and more cancer survivors will experience CIPN leading to chronic pain and worsening quality of life. However, the available and effective strategies for clinical treatment of CIPN are very limited. Oncologists are frequently obliged to decrease or stop neurotoxic anticancer drugs, with a possible deleterious impact on the oncological prognostic. The challenges faced by CIPN include further study on the pathological mechanism, dose threshold, incidence, risk factors and clinical characteristics of CIPN; lack of diagnostic criteria and tools of CIPN; lack of effective and standardized CIPN prevention and treatment programs. The current update of research results on these challenging issues of CIPN will provide more decision-making evidence for oncologists to diagnose and treat CIPN. Therefore, Committee of Neoplastic Supportive-Care of China Anti-Cancer Association and Cancer Clinical Chemotherapy Committee of China Anti-Cancer Association convenes some experts to summarize the recent literatures and discuss to reach the consensus about recommendations for the definition, pathophysiological mechanism, assessment, prevention, and treatment of CIPN.
Antineoplastic Agents/adverse effects* ; Consensus ; Humans ; Neoplasms/drug therapy* ; Peripheral Nervous System Diseases/prevention & control* ; Quality of Life

OBJECTIVE: To evaluate the efficacy of Wen-Luo-Tong Granules (WLT) local administration in the treatment of patients with peripheral neuropathy (PN) induced by chemotherapy or target therapy. METHODS: This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT (39 cases) and control groups (39 cases) using a block randomization method. The WLT group received WLT (hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (QLQ-CIPN20), and Quality of Life Questionnaire-Core30 (QLQ-C30). RESULTS: After treatment, the PN grade in the WLT group was significantly lower than that in the control group (1.00 ± 0.29 vs. 1.75 ± 0.68, P<0.01). The total effective rate in the WLT group was significantly higher than that in the control group (82.05% vs. 51.28%, P<0.01). Compared with the control group, the touch-detection thresholds at fingertips, neuropathy symptom score, QLQ-CIPN 20 (sensory scale, motor scale, autonomic scale, and sum score), and QLQ-C30 (physical functioning, role functioning, emotional functioning, and global health) in the WLT group significantly improved after treatment (P<0.01 or P<0.05). CONCLUSION WLT local administration was significantly effective in the treatment of patients with PN induced by chemotherapy or target therapy. (Trial registration No. ChiCTR1900023862).
Antineoplastic Agents/adverse effects* ; China ; Humans ; Japan ; Peripheral Nervous System Diseases/drug therapy* ; Quality of Life/psychology* ; Surveys and Questionnaires