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25 August 2023, Volume 22 Issue 04 Previous Issue    Next Issue

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New knowledge of prophylaxis and treatment about cancer-associated thrombosis DING Yongjie, ZHANG Liu, LI Qingyun 2023, 22 (04):  323-331.  DOI: 10.16150/j.1671-2870.2023.04.001 Abstract ( 148 )   HTML ( 13 )   PDF (946KB) ( 2397 )   Cancer-associated thrombosis (CAT) is the second leading cause of death in cancer patients, second only to the progression of the tumor. It leads to extended hospitalization and re-hospitalization, resulting in a serious social medical burden. Tumor-specific gene mutations such as JAK2, ALK, and KRAS mutations are closely related to the risk of CAT in patients with solid tumors. Patients treated with immune checkpoint inhibitors have a high risk of CAT, with a 1-year cumulative incidence rate of 10.86%. Therefore, accurate risk assessment is important. The Khorana risk score (KRS) is the first model to assess CAT risk and has been validated in several studies. The new generation models are based on the improvement of KRS, but they have not yet undergone large-scale external verification, such as the Vienna CAT model, PROTECHT model, and CONKO model. Due to the strong correlation between tumors and CAT, several CAT-related prevention guidelines have been established domestically and abroad. All of these guidelines recommend that patients undergo preventive anticoagulation therapy after tumor surgery. Low molecular weight heparin (LMWH) is the most widely used anticoagulant drug to prevent CAT. New oral anticoagulants (NOAC) are also used to prevent CAT, despite the incidence of hemorrhaging increases, the overall benefits to patients outweigh the risks. The strategy for treating CAT is complex. For patients with non-gastrointestinal tumors, NOAC can be used as a first-line drug, while LMWH is recommended for anticoagulation in patients with gastrointestinal tumors. Since CAT patients receive anticoagulation and anti-tumor therapy at the same time, drug interactions need to be considered to avoid drug-induced bleeding, especially the impact of combined medication on NOAC pharmacokinetics. The ideal length of anticoagulation therapy for CAT remains unclear. Guidelines recommend that patients with CAT should indefinitely continue the anticoagulation therapy after completing 3 to 6 months of initial anticoagulation therapy. Therefore, when determining the course of anticoagulation therapy for cancer patients, physicians should evaluate the risk of recurrence of thrombosis and bleeding, and optimize the treatment plan. Figures and Tables | References | Related Articles | Metrics

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Clinical application of circulating tumor cells in gastric cancer: advances and prospects LI Yilin, CHEN Yang, LI Yanyan, FENG Xujiao, ZHANG Cheng, LI Jian, SHEN Lin 2023, 22 (04):  332-340.  DOI: 10.16150/j.1671-2870.2023.04.002 Abstract ( 102 )   HTML ( 5 )   PDF (942KB) ( 101 )   Malignant tumors seriously threat the health of the Chinese population. Circulating tumor cell (CTC), as molecular markers in liquid biopsy, have the advantage of being non-invasive and longitudinal monitoring of tumor progression and efficacy. In vitro CTC enrichment detection methods are divided into two types: based on molecular characteristics and based on physical characteristics. In recent years, a series of comprehensive CTC enrichment methods targeting different molecular characteristics have been developed, as well as the use of subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) for enrichment detection of gastric cancer CTC. Microfluidic technology can separate and enrich CTC on the same chip based on their molecular and physical characteristics simultaneously, helping to achieve more efficient and sensitive CTC enrichment detection. Compared with the in vitro CTC enrichment platform, the in vivo CTC enrichment platform has higher capture efficiency and detection sensitivity, but it is an invasive examination, and the impact on patients still needs further study. High CTC level is closely related to the disease control rate after gastric cancer chemotherapy and is an independent predictor of poor prognosis in gastric cancer patients. Among non-metastatic malignancies, increased CTC counts after surgery in patients with esophageal cancer and colorectal cancer are strongly associated with worse overall survival. Since CTC are highly heterogeneous, changes in CTC can be longitudinally monitored to provide a reference for the treatment of malignant tumors. Research on gastric cancer has shown that the positivity rate, size of circulating tumor microemboli (CTM) and gene expression level of CTC are closely related to the ability of invasion, metastasis, drug resistance and prognosis. The dynamic metastasis process and pattern of CTC play an important role in tumor metastasis. For the detection of CTC, it is necessary to establish unified standards and verification methods, and develop multi-omics research technology. References | Related Articles | Metrics

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The application value of determination of hemostasis and thrombosis in tumor patients WANG Yanchun, LU Renquan 2023, 22 (04):  341-347.  DOI: 10.16150/j.1671-2870.2023.04.003 Abstract ( 107 )   HTML ( 4 )   PDF (913KB) ( 75 )   Abnormal coagulation function is an important feature of the occurrence and development of malignant tumors. Tumor cells release pro-angiogenic factors that cause vascular endothelial damage and induce platelet activation and proliferation, all of which increase the risk of thrombosis. Cancer patients often present with shortened APTT and PT, elevated fibrinogen, D-dimer and platelet counts, and a hypercoagulable state. With thrombosis forms, the fibrinolytic system is activated, and D-dimer and fibrin degradation product (FDP) increase. Both are commonly used markers of the fibrinolytic system. FDP/D-dimer ratio may improve the accuracy of diagnosing thrombosis or bleeding. New coagulation markers, such as platelet function and platelet surface markers, can be used to assess platelet activation. During the hypercoagulable state and the fibrinolysis process of tumors, four new thrombosis factors are discovered: thrombin-antithrombin (TAT), plasmin α2-plasmin inhibitor complex (PIC), tissue plasminogen activator-inhibitor 1 complex (t-PAIC) and thrombomodulin, which can be used as diagnostic markers for malignant tumors and thrombosis. Thromboelastography simultaneously reflects coagulation factor activity, fibrinogen activity, platelet counts and function, and demonstrates the overall dynamic process of coagulation and fibrinolysis. The 6 traditional coagulation tests combined with platelet count, the 4 new thrombosis tests combined with D-dimer and FDP tests, as well as various thrombosis risk assessment models, play an important role in the prognosis assessment of different tumors. With the development of artificial intelligence and new indicators, the application prospects of coagulation abnormality detection will be broader. References | Related Articles | Metrics

Academic trend at home and abroad

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The diagnostic threshold for hypertension should not be lowered down to 130/80 mmhg: an academic perspective SHI Zhongwei 2023, 22 (04):  348-361.  DOI: 10.16150/j.1671-2870.2023.04.004 Abstract ( 50 )   HTML ( 4 )   PDF (1848KB) ( 35 )   Hypertension is a clinical diagnosis and is defined as the level of blood pressure (BP) at which the benefits of treatment unequivocally outweigh the risks of treatment, as documented by randomized controlled trials (RCTs). According to the current Chinese hypertension guidelines, the office BP threshold for diagnosing hypertension is systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg. However, in the 2017 ACC/AHA hypertension guidelines the diagnostic threshold for hypertension was reduced to ≥130/80 mmHg with purpose of promoting more intensive BP treatment. Some Chinese experts suggest to adopt this new standard, but many more point out that such a change will impact severely on our healthcare system. This paper will explain why the BP threshold should not be lowered down to 130/80 mmHg from an academic perspective.During the past several decades a large number of RCTs have shown that, in hypertensive patients with drug treatment, lowering SBP/DBP to <140/90 mmHg is associated with significant reductions in major cardiovascular (CV) events and all-cause mortality. In 2003 American hypertension guidelines (JNC 7) recommended to treat patients with diabetes or chronic kidney disease (CKD) to BP goal of <130/80 mmHg. However, European experts found that recommendation was not supported by RCT evidence. The 2014 evidence-based American guidelines (JNC 8) drew the same conclusion and recommended a BP goal of <140/90 mmHg for hypertensive persons young than 60 years, including those with diabetes or CKD. The six recently published RCTs showed different results. Lowering SBP to <130/80 mmHg in patients with recent lacunar stroke did not result in a significant reduction of recurrent stroke in the SPS3 trial. Targeting a SBP of <120 mmHg did not reduce the rate of major CV events in the ACCORD study. Both the HOPE-3 trial and the CHINOM trial showed that in low-to-moderate risk patients with a BP in the high-normal range, antihypertensive drug treatment was not associated with a lower rate of major CV events than placebo. The SPRINT trial and the STEP study showed that intensive treatment with a SBP target of <120 mmHg or <130 mmHg resulted in a lower incidence of CV events. SPRINT trial was the major driver for the BP threshold changes introduced in the 2017 ACC/AHA guidelines. However, in the SPRINT trial a unique unattended BP measurement method was used that was different from methods used in previous studies. The SBP levels, when assessed by the unattended method, are usually much lower than when measured with conventional office BP measurement. Both the SPRINT trial and the STEP study are open-labelled and stopped early that typically provide exaggerated estimates of benefits. Both the studies required that patients in the standard treatment group stop taking antihypertensive drugs or have the doses reduced if their SBP dropped to below the lower limit of the target range. Reduction of therapy is not in line with clinical practice and would seem to bias the trial against the standard treatment. Thus, there still lacks high-quality evidence to convince us to reset the diagnostic threshold for hypertension to 130/80 mmHg, down from the current trigger of 140/90. Figures and Tables | References | Related Articles | Metrics

Original articles

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Clinicopathological features and prognosis of 17 cases of duodenal-type follicular lymphoma LIU Yingting, YI Hongmei, WANG Xue, YANG Chunxue, OUYANG Binshen XU Haimin, WANG Chaofu 2023, 22 (04):  362-368.  DOI: 10.16150/j.1671-2870.2023.04.005 Abstract ( 140 )   HTML ( 13 )   PDF (7712KB) ( 79 )   Objective: To investigate the clinicopathological features and prognosis of duodenal-type follicular lymphoma (DFL). Methods: The clinical features, endoscopic appearances, pathological features, and treatments of 17 patients with DFL were retrospectively analyzed and followed up. Results: Among the 17 cases of DFL, there were 8 males and 9 females, with a male-to-female ratio of 1∶1.125. The median age was 58 years (33-67 years). Among them, 13 patients with DFL were found in routine physical examination, and most of them showed granular hyperplasia under endoscopy. Among the cases, 15 (88.2%) occurred in the duodenum, and all were located in the descending part of the duodenum. There were 15 cases of single lesions and 2 cases of multiple lesions. Under the microscope, the lesions were located in the mucosal layer or submucosal layer, with a clear or vague “expansive” growth pattern and visible follicular nodules. The nodules were composed of centrocyte-like cells and scattered centroblast-like cells, equivalent to grade 1 or 2 of classical follicular lymphoma. The tumor cells expressed CD20, CD79a, CD10, BCL6, and BCL2. CD21 staining of 9 cases showed that the follicular dendrite network was densely stained around the neoplastic follicles, but lightly stained and sparse in the center. Ki-67 expression was low. Four cases underwent second-generation gene sequencing, among which three cases had detected CREBBP gene mutations. Fourteen cases did not receive any treatment, and disease did not progress. One case underwent local intestinal segment resection without postoperative chemotherapy or radiotherapy and did not relapse. One case received chemotherapy and rituximab treatment, and the lesion completely disappeared. Conclusions: Most of DFL lesions are single lesions with microscopic manifestations similar to those of typical follicular lymphoma grade 1 or grade 2. The special immunophenotype is CD21, which is often more dense and deeply stained around the neoplastic follicles, and has inert biological behavior. Figures and Tables | References | Related Articles | Metrics

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Value of ultrasound in the etiological diagnosis of azoospermia YAO Shifa, CHEN Ping, LI Liang, NIU Jianmei 2023, 22 (04):  369-373.  DOI: 10.16150/j.1671-2870.2023.04.006 Abstract ( 71 )   HTML ( 5 )   PDF (2356KB) ( 59 )   Objective: To explore the application value of ultrasound in the etiological diagnosis of azoospermia.Methods: Three hundred and fourteen consecutive cases of azoospermia diagnosed in our hospital from January 1, 2015 to December 31, 2021 were retrospectively analyzed, and their clinical data and ultrasonic examination results were summarized and analyzed. Results: Among 314 patients, 118 (37.6%) had obstructive azoospermia (OA) and 196 (62.4%) had non obstructive azoospermia (NOA). Among OA patients, 89% (105 cases) showed positive ultrasound findings, including congenital bilateral vas deferens absence (40 cases), ejaculatory duct obstruction(33 cases), inflammatory lesions(17 cases), and calcified lesions (15 cases); Among 196 patients with NOA, 40.3% (79 cases) had positive ultrasound findings, including small testis (45 cases), cryptorchidism (13 cases), testicular microlithiasis (16 cases), and varicocele (5 cases). Conclusions: Among the 314 patients with azoospermia in this study, the ratio of NOA to OA is 1.66:1. Ultrasound examination is able to identify the etiology of 58.6% of the patients, including 89% of the causes of OA and 40.3% of the causes of NOA. Figures and Tables | References | Related Articles | Metrics

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Establishment and verification of reference range of parameters related to uterine artery measured by ultrasound at 11~40 weeks of pregnancy GONG Xiaoping, CAO Yunyun, WANG Haifei, WANG Guanjie, ZENG Min 2023, 22 (04):  374-378.  DOI: 10.16150/j.1671-2870.2023.04.007 Abstract ( 86 )   HTML ( 6 )   PDF (900KB) ( 98 )   Objective: To establish and verify the normal reference range of uterine artery mean pulsatility index (mPI) between 11-40 weeks of pregnancy in low-risk population. Methods: Pregnant women registered in our hospital from January 2019 to July 2023 and underwent ultrasound examination at 11 to 40 weeks were enrolled. By Ultrasound diagnosis, the pulsatility index (PI) of bilateral uterine arteries were measured, and whether there was a notch in the early diastolic period was checked. Following up the pregnancy, basic clinical data and fetal birth information were collected. Results: A total of 1365 low-risk people with normal pregnancy outcomes were included. The 104 cases of adverse pregnancy outcomes were wed to verify the refernce range, including pregnancy included hypertension (n=41) and fetalgrowth restriction (n=23). With the increase of gestation age, mPI showed a gradual downward trend. There was a rapid decline before 20 weeks of gestation (mPI 95th percentile at 11 weeks and 20 weeks of gestation were 2.35 and 1.54, respectively), then declined slowly, and mPI stabilized after 32 weeks of gestation (95th percentile mPI at 32 weeks and 39 weeks of gestation were 0.91 and 0.87, respectively). With the increase of gestation age, the detection rate of early diastolic notch in bilateral uterine arteries decreased gradually. The detection rate was 69.20% at 11-15 weeks of gestation, 27.01% at 21-25 weeks of gestation, then stabilized and decreased to 6.31% at 36-40 weeks of gestation. The results of receiver operating characteristic (ROC) curve analysis showed that the sensitivity and specificity of mPI ≥95th precentile in predicting hypertensive disorder complicating pregnancy were 30.11% and 93.21%, respectively; The sensitivity and specificity in predicting fetal growth restriction were 61.9% and 92.85%, respectively. Conclusions: Establishing the reference range of uterine artery mPI at 11-40 weeks of pregnancy in low-risk population may be used for prospective exclusion of gestational hypertension and fetal growth restriction. Figures and Tables | References | Related Articles | Metrics

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Establishing reference intervals of four routine coagulation indicators in healthy Chinese adults YAO Yong, DONG Zhenghua, FAN Houzhen, GAO Yunqin, LIU Qian, WU Jun 2023, 22 (04):  379-384.  DOI: 10.16150/j.1671-2870.2023.04.008 Abstract ( 123 )   HTML ( 6 )   PDF (963KB) ( 89 )   Objective To establish four coagulation indicators suitable for Chinese adults, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB). Methods Representative medical institutions from East and North China were selected. A total of 668 Chinese healthy adults were enrolled from Shanghai Oriental Hospital (South Campus), Beijing Jishuitan Hospital and Linyi Hospital of Traditional Chinese Medicine in this study. The cobas t 711 platform was used to detect the four coagulation indicators, and reference intervals were established based on the results. Results The reference interval applicable to all enrolled population was established: APTT (s): 26.6-43.6 s, PT (s): 7.67-10.5, TT (s): 14.5-19.2, FIB (mg/dL): 193-419. The four coagulation indicators were statistically different in different regions, genders and ages. In the gender analysis, difference in PT was the most significant (P<0.001). PT and APTT were higher in the male group, and FIB was higher in the female group; Taking ≤50 years as the cut-off age, APTT, FIB were statistically higher in the elderly group (>50 years old); There were statistical differences in APTT, FIB, PT, and TT in different regions (Shanghai, Beijing, and Shandong) (P<0.001). The median APTT and FIB were highest in Shanghai (P<0.001), the median PT was highest in Beijing (P=0.001), and the median TT was highest in Shandong. Conclusions The reference interval of four coagulation indicators suitable for Chinese healthy adult population is established. Factors that influencing the reference intervals include region and age. Reference intervals between male and female overlaps,and reference intervals establishment depends on laboratory conditions, influencing factors (region, and age) on coagulation management. Figures and Tables | References | Related Articles | Metrics

Case reports

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Adult colonic duplication with epithelial low grade dysplasia: a case report JIN Zhe, TANG Feng, DU Zunguo 2023, 22 (04):  385-388.  DOI: 10.16150/j.1671-2870.2023.04.009 Abstract ( 67 )   HTML ( 5 )   PDF (1927KB) ( 41 )   Enteric duplication is a rare malformation of the digestive tract, while colonic duplication is even rarer in adults. This paper reports one case, a 22-years old female, presented with a peritoneal cystic mass lesion measured 15 cm×10 cm. The lesion was found to be from the mesentery of the colon during surgery, and sharply demarcated. It was revealed by histopathology that the cystic wall was characterized by colonic muscularis propria and mucosa layer, in which epithelium showed low-grade dysplasia, accompanied by inflammatory reactions, and lack of distinct differentiation components into other organs. Colonic duplication with epithelial low-grade dysplasia was diagnosed. The author will analyze the clinicopathological features of colonic duplication combined with literature review. Figures and Tables | References | Related Articles | Metrics

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Thoracic SMARCA4-deficient undifferentiated tumour: a case report ZHANG Lanlan, YANG Qiao, NIE Zunzhen, GUO Ying 2023, 22 (04):  389-392.  DOI: 10.16150/j.1671-2870.2023.03.010 Abstract ( 155 )   HTML ( 2 )   PDF (3596KB) ( 101 )   Thoracic SMARCA4-deficient undifferentiated tumor is a rare type of undifferentiated tumor occurring in the pleura. Their morphological features are poorly differentiated. A malignant tumor that lacks glandular, squamous, or other distinct cell lineages, as demonstrated by histological and immunohistochemical staining, is characterized by plasmacytoid and rhabdomytoid cell morphology and loss of SMARCA4 expression. We report a case of an undifferentiated tumor in the pleura with a SMARCA4 deletion,The tumor cells were plasmacytoid or rhabdomytoid，Poor cell differentiation, Immunohistochemical staining showed Syn positive in tumor cells,SMARCA4 expression is deficient,The proliferation index of Ki-67 was 80%,Other markers were all negative The patient was a heavy smoker and previously healthy.Patients with insidious onset,It was found in an advanced stage.After the surgery, no treatment was administered, and the patient survived for only 66 days.There was no significant difference in the survival time of advanced patients who received traditional treatment after surgery compared with those reported in the literature.The clinical data, histological characteristics and immunohistochemistry were retrospectively analyzed, and a review of the relevant literature suggests that SMARCA4-deficient undifferentiated tumors are highly aggressive and have a poor prognosis. Figures and Tables | References | Related Articles | Metrics

Review articles

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DNA methylation detection assists early screening and diagnosis of tumors LIU Yifei 2023, 22 (04):  393-401.  DOI: 10.16150/j.1671-2870.2023.04.011 Abstract ( 471 )   HTML ( 14 )   PDF (1010KB) ( 310 )   DNA methylation is one of the most widely used indicator for early cancer screening. Under the influence of carcinogens, hypermethylation of the promoter region of tumor suppressor genes may lead to downregulation or silencing of gene expression, thereby activating the expression of proto-oncogenes and promoting tumorigenesis. The samples used for DNA methylation detection are mainly exfoliated cells, blood samples and paraffin-embedded tissues. Commonly used detection methods include: methylation-specific polymerase chain reaction (MSP), nucleic acid mass spectrometry, methylation chip, bisulfite sequencing, next-generation sequencing, etc. Compared with mutation detection, the advantages of DNA methylation detection are that it has higher tumor specificity, more detectable sites, higher signal quality, and can achieve tissue traceability. Currently, it is mainly used clinically for medication guidance for brain glioma, aid in diagnosis and high-risk triage for lung cancer, high-risk triage and recurrence monitoring for bladder cancer, high-risk triage for cervical cancer, and early screening and recurrence monitoring for colorectal cancer and gastric cancer. Before large-scale clinical routine application, accurately positioning of the application scenarios for DNA methylation detection must be considered. For well-tolerated endoscopy, the rigid need of DNA methylation detection for high-risk triage may be reduced. DNA methylation detection plays an important role in assisting in the diagnosis of tumors with low pathological diagnosis sensitivity, tumor monitoring and prognosis assessment. With the standardization of testing procedures and quality management, DNA methylation detection will be more widely used to improve the early screening and diagnostic sensitivity of tumors. Figures and Tables | References | Related Articles | Metrics

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Current status and research progress of diagnosis and treatment of AIDS with disseminated non-tuberculous mycobacterial disease HU Jingjing, SHEN Yinzhong, LIU Li, LU Hongzhou 2023, 22 (04):  402-406.  DOI: 10.16150/j.1671-2870.2023.04.012 Abstract ( 63 )   HTML ( 8 )   PDF (956KB) ( 44 )   Non-tuberculous mycobacteria (NTM), an opportunistic pathogen, generally rarely causes disease in immunocompetent populations unless host immune defenses are compromised. Acquired immune deficiency syndrome (AIDS) patients have a severe deficiency in immune function due to the destruction of CD4+ T lymphocytes by human immunodeficiency virus (HIV) in the body. When patients are infected with NTM, NTM is likely to colonize and eventually lead to disseminated NTM disease (DNTM). In recent years, the number of tuberculosis patients worldwide has been on a downward trend. However, the number of AIDS patients with NTM is on the rise with the AIDS epidemic, the increase in the number of immunosuppressed people, and the continuous advances in laboratory techniques for NTM testing. Compared with tuberculosis, our public health administration system has not incorporated NTM infection into the reporting system, and the previous clinical attention was insufficient, so the systematic studies are limited. The 5-year case fatality rate of AIDS patients with DNTM in some areas of China was as high as 26.7%. The disease is a great threat to patients' life and health, and consumes a lot of medical resources. At present, China still faces great challenges in differential diagnosis, treatment, and high fatality rate of NTM. Therefore, it is urgent to strengthen the clinical knowledge of DNTM and improve disease prevention and control as well as clinical response capabilities. In this study, the recent research progress of DNTM was reviewed to provide a reference and basis for clinicians to diagnose and treat AIDS with DNTM. References | Related Articles | Metrics

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Advancements in M protein interference in the clinical laboratory detection PAN Xiaoyuan, SHI Hui, CAO Jijun, SHI Xinming, SHI Ce 2023, 22 (04):  407-411.  DOI: 10.16150/j.1671-2870.2023.04.013 Abstract ( 79 )   HTML ( 7 )   PDF (893KB) ( 62 )   M protein is a unique immunoglobulin type that often affects the laboratory results of certain blood tests. The M protein interference exits in the pre-analytical, analytical and post-analytical process, seriously affecting the accuracy of tests. For example, high concentrations of M protein in serum creatinine, uric acid, lipoprotein, total protein, bilirubin, blood glucose, phosphorus, hemoglobin, glycosylated albumin can cause false high or false low results. The abnormal presence of M protein in 25-OH vitamin D, thyroid-stimulating hormone, c-reactive protein, vancomycin, gentamicin and sodium valproate concentrations interferes with the actual detection results. Solutions to the above problems include diluting serum or removing protein before testing, using protein stabilizers during testing or optimizing reaction conditions. Furthermore, in clinical practice, hidden M protein can be uncovered, and effective detection prior to the onset of disease can open new avenues for disease management and prognosis. Figures and Tables | References | Related Articles | Metrics