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Objective:To investigate the clinical characteristics of de novo malignancies (DNMs) after liver transplantation (LT) and to study the clinical management strategies.Methods:Adult LT recipients who were regularly followed-up in the Organ Transplantation Center, the Affiliated Hospital of Qingdao University from January 2005 to April 2021 were enrolled in this study. The clinical characteristics of DNMs were retrospectively analyzed. Of 601 LT recipients, there were 105 females and 496 males, aged (51.4±9.6) years old. They were divided into the DNMs group ( n=26) and the non-DNMs group ( n=575) according to whether there were DNMs on followed-up. Clinical data including age, sex, basic diseases before LT and operation time were collected. These patients were follow-up in outpatient clinics. Results:Twenty-six patients were diagnosed to develop DNMs after LT, but there were 28 DNMs (of which 2 patients were diagnosed to have DNMs twice). The incidence of DNMs after LT was 4.3% (26/601), the median time from LT to DNMs was 42 (20, 70) months, and the cumulative incidence rates of DNMs were 0.5%, 2.0%, 6.3%, 21.0% and 34.5% at 1, 3, 5, 10 and 15 years after LT, respectively. Among the 28 DNMs, digestive system tumors were most common, with 17 lesions (60.7%), followed by 3 lesions (11.1%) of lung cancer, 2 lesions (7.4%) of lymphoproliferative diseases, and 1 lesion (3.7%) of cervical cancer, thyroid cancer, soft palate cancer, eyelid cancer, laryngeal cancer, and prostate cancer. The follow-up time of 55.9 (36.6, 102.5) months in the DNMs group after LT was longer than the 33.4 (18.5, 58.9) months in the non-DNMs group ( P<0.001). The 1, 5, and 10 year survival rates of patients with DNMs after LT were 96.3%, 83.5%, and 49.8%, respectively. The 1, 5, and 10 year survival rates of patients with non-DNMs after LT were 94.5%, 77.7%, and 75.4%, respectively. There was no significant difference in the cumulative survival rates between the two groups (log rank=0.402, P=0.526). Conclusion:The incidence of DNMs in LT recipients was 4.3%. The majority of them were digestive system tumors. Early diagnosis and treatment of DNMs significantly improved the prognosis and quality of life of these patients.
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Objective:To explore the clinical applications and therapeutic outcomes of immune checkpoint inhibitors(ICIs)on liver transplantation(LT)recipients after tumor development.Methods:Eight databases including PubMed, China National Knowledge Infrastructure, Wanfang Data, CQVIP, PubMed, EMBASE, Web of Science and Google scholar were accessed for searching the relevant literature articles in both Chinese and English from the establishment of databases to December 31, 2021. Disease response, adverse reactions and prognoses of patients with malignant tumors after LT and receiving ICIs were analyzed.Results:The patient was diagnosed as chronic rejection plus drug-induced liver injury by liver biopsy. After intermittent treatment with DPMAS plus plasma exchange and immunosuppressants, he finally died of tumor recurrence at 37 months after LT. After screening, a total of 28 articles on the application of ICIs after LT were retrieved. In these articles, there were 47 patients(37 males and 10 females)with a median age of 57(14-71)years and the predominant type of tumor after LT was hepatocellular carcinoma(28/47, 59.6%), followed by malignant melanoma in 11 cases (23.4%), non-small cell lung cancer in 3 cases(6.4%), colorectal cancer, cholangiocarcinoma, squamous cell carcinoma, hypopharyngeal squamous cell carcinoma and post transplant lymphoproliferative disease(PTLD) in 1 case(2.1%). The overall remission rate after ICI treatment was 29.8%(14/47)and the disease progression rate 68.1%(32/47). Among them, 31.9%(15/47)had immune rejection. Case fatality rate was 61.7%(29/47)and median survival time 6.5(0.3-48.0)months.Conclusions:Depending on existing publications, among those LT recipients with malignant tumors treated by ICIs, the rate of graft rejection and patient mortality are higher. ICIs should be carefully considered for LT patients and further researches are required.
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Objective To analyze the incidence and risk factors of colorectal adenomatous polyps (CAP) in recipients after liver transplantation. Methods Seventy-seven liver transplant recipients and 231 individuals undergoing colonoscopy during physical examination were recruited in this study. The incidence of CAP and pathological examination results were analyzed. Clinical data of liver transplant recipients were collected. According to the incidence of CAP, liver transplant recipients were divided into the CAP group (n=28) and non-CAP group (n=49). The risk factors of CAP after liver transplantation were identified. Results The 5-year cumulative incidence rates of colorectal polyps in liver transplant recipients and physical examination individuals were 43% and 34%, and 29% and 23% for the 5-year cumulative incidence rates of CAP, with no significant differences (both P > 0.05). Among all liver transplant recipients, 65 polyps were detected. The quantity of polyps in 1 case was excessively high and not counted. Multiple polyps were identified in certain recipients. Five polyps were not prepared for pathological examination due to small size. Pathological examination of 60 polyps demonstrated 25 inflammatory polyps, 33 CAP (8 complicated with low-grade intraepithelial neoplasia and 3 complicated with high-grade intraepithelial neoplasia), and 2 well-differentiated adenocarcinoma. Cox model analysis prompted that use of ciclosporine after liver transplantation was an independent risk factor for CAP in the recipients. Conclusions The risk of CAP is slightly elevated after liver transplantation. Postoperative use of ciclosporine is an independent risk factor for CAP in recipients after liver transplantation. Colonoscopy should be emphasized in the recipients after liver transplantation.
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Objective:To determine the prevalence of Helicobacter pylori (Hp) infection in orthotopic liver transplantation (LT) recipients, and to study the efficacy and safety of Hp eradication therapy.Methods:13C-urea breath test was carried out between July 2018 and October 2019. There were 104 males and 26 females with an average age of 52.1 year for these LT recipients who were regularly followed-up in the Organ Transplant Center, the Affiliated Hospital of Qingdao University. Propensity scoring was used to match age and gender in a ratio of 1∶3. A healthy group of individuals consisting of 299 males and 91 females, with an average age of 51.8 years, were selected as the control group also in a ratio of 1∶3. All patients underwent 13C-urea breath test to evaluate Hp infection and results of quadruple therapy. Results:The prevalence of Hp infection among the LT recipients was 18.5%(24/130) which was significantly lower than the control group 36.4% (142/390) (χ 2=14.400, P<0.001). Among the recipients who received LT and 13C-urea breath test for less than 1 year, 1-3 years and more than 3 years, the prevalences of Hp infection were 14.3% (6/42), 17.8%(8/45) and 23.3%(10/43), respectively. Although the prevalence of Hp showed a gradually increasing trend, no correlation between Hp infection and duration from LT was observed (χ 2=1.321, P=0.517). Seventeen Hp positive recipients underwent Hp eradication therapy. The success rate of Hp eradication was 100.0%(17/17). Immunosuppressant concentration was monitored regularly in 10 patients. During Hp eradication, the blood concentration of immunosuppressant increased from 1.7 to 3.6 times, and the drug dosage was reduced to one half to one third of what it was before Hp eradication. Seven of these 17 recipients suffered from adverse effects caused by increased levels of blood concentration of immunosuppressants, including headache, hypertension, insomnia and irritability. Normal liver and kidney functions were observed during eradication. Conclusion:In this study, the prevalence of Hp infection among liver transplant recipients was 18.5%. The success rate of Hp eradication was 100% using bismuth-containing quadruple therapy. The dosage of immunosuppressant required to be monitored, and if necessary, adjusted during eradication to reduce adverse side effects.
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Objective To investigate the incidence of de novo malignant tumors of the digestive system after liver transplantation (LT) in China. Methods Relevant literature review was performed from Wanfang data, China National Knowledge Infrastructure (CNKI) and Chongqing VIP. The retrieval time started from the establishment of each database to May 9, 2019. The Chinese search terms were liver transplantation+ postoperative/de novo+ malignant tumor/cancer. The age distribution, sex composition, time of diagnosis, involved organs, treatment and clinical prognosis of recipients with de novo malignant tumors of the digestive system after LT in China were retrospectively analyzed. Results After literature screening, 16 articles were eventually selected including 47 cases of de novo malignant tumors of the digestive system after LT. A majority of them were male recipients. The age of the recipients was 51 (23-65) years old, most of them were middle age (45-59 years old). The average time of diagnosis of de novo malignant tumors of the digestive system after operation was 43 (2-156) months, with the highest number of cases within postoperative 1-3 years. Colon and stomach were the most common tumor sites. Surgery combined with radiotherapy and chemotherapy remained the main treatment option. However, the overall clinical prognosis of patients with de novo malignant tumors of the digestive system after LT was poor with a mortality rate of 51%. Conclusions In China, colon cancer and gastric cancer are the main de novo malignant tumors of the digestive system after LT. The overall clinical prognosis of patients with de novo malignant tumors of the digestive system is poor. Sufficient attention should be paid to postoperative monitoring and prevention.
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Objective:To summarize the experience of diagnosing and treating de novo gastric cancer after liver transplantation(LT).Methods:The clinical data were analyzed for 3 LT patients with de novo gastric cancer during follow-ups.Results:The mean diagnostic age was 57(47~67)years, mean time interval between LT and diagnosis of de novo gastric cancer 82(40~122)months and mean follow-up time 23(4~42)months. After surgical resections, 2 survived and another died of recurrence.Conclusions:LT recipients are recommended for regular screening of de novo malignancies. Regular endoscopic screening of gastric tumors contributes to early detection, diagnosis and treatment. It may improve long-term survival outcomes in LT recipients.
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PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules. Finally, nude mice subcutaneous transplantation tumor model was used to confirm the therapy efficacy of PAB. RESULTS: PAB could inhibit SW1990 cell proliferation and invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin, Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p < 0.01), while E-cadherin, caspase-9, MST1, and pYAP were up-regulated (p < 0.05). Combined PAB and gemcitabine treatment markedly restricted the tumor growth compared with gencitabin or PAB alone groups. CONCLUSION: PAB could inhibit the proliferation and invasion ability of pancreatic cancer cells through activating Hippo-YAP pathway and inhibiting the process of EMT.
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Animals , Female , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/metabolism , Cadherins , Cell Line, Tumor , Cell Movement , Cell Proliferation/drug effects , Cytokines , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Diterpenes/pharmacology , Diterpenes/therapeutic use , Epithelial-Mesenchymal Transition/drug effects , Mice, Nude , Neoplasm Invasiveness , Pancreatic Neoplasms/diet therapy , Pancreatic Neoplasms/pathology , Real-Time Polymerase Chain Reaction , Signal Transduction/drug effects , Vimentin/metabolismABSTRACT
Objective To study the efficacy and safety of carotid endarterectomy ( CEA) in the treatment of carotid artery stenosis with different neurological deficits .Methods The clinical data of 59 patients with carotid stenosis treated by carotid endarterectomy in the department of neurosurgery of affiliated hospital of Xuzhou medical university from September 2015 to February 2017 were analyzed retrospectively ,a total of 62 operations were performed in these patients ( including 3 patients accepted bilateral operation ) .According to the preoperative 1 day nerve function which evaluated by the modified Rankin scale (mRS)score,they were divided into mRS <3 group(n=47),mRS≥3 group (n=15).They were followed up for 6 to 24 months,the neurological function of 62 patients was scored again by mRS at 6 months after sur-gery.The clinical data and the difference of surgical efficacy and safety of perioperative period between the 2 groups were analyzed and com-pared.Results The 62 times of operations were successful in patients .The neurological function of the 2 groups were significantly improved compared with the preoperative,the difference was statistically significant(P<0.05).In the mRS≥3 group,there were 1 patients with perio-perative cerebral infarction died of cerebral hernia ,1 case of consciousness disorder caused by high perfusion and 1 cases of postoperative in-tracranial hemorrhage caused by high perfusion .In the mRS<3 group,there was 1 case left contralateral hemiplegia caused by a large area of cerebral infarction .The incidence of cerebral apoplexy within 30 days after procedure in the mRS≥3 group was significantly higher than that in the mRS<3 group.There was no new stroke in 61 patients during the long-term follow-up.Conclusion Mild(mRS<3) and severe(mRS≥3) of patients has improved nervous function from CEA;perioperative risk of patients with severe neurological deficits is relatively higher , but the preventive effect for the prevention of ischemic stroke recurrence is worthwhile .
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Objective To explore the risk factors,the distribution of etiology and drug resistance status of patients with early infection (3 months) after liver transplantation,and to provide reference for clinical diagnosis and treatment.Methods The clinical data of 112 recipients from February 2014 to December 2015 were collected,and logistic regression analysis was performed on the risk factors of early postoperative infection in liver transplant patients.The independent risk factors of infection after liver transplantation were screened out.At the same time,the results of pathogen culture and drug sensitivity test were statistically described.Results The independent risk factors for infection at 3th month after liver transplantation included the operative time ≥600 min [P =0.003,odds ratio (OR) =9.996,95 ％ confidence interval (95 ％ CI),2.221-44.981],intensive care unit (ICU) ≥6 days (P =0.010,OR =6.306,95％ CI =1.563-25.437),Child-Pugh grade of C (P =0.023,OR =6.298,95％ CI =1.294-30.659).Of the 112 liver transplant recipients,59 had an infection (52.68％),and 168 stains of pathogens were isolated.The positive rate of the specimens was highest in sputum,followed by bile,ascites,drainage and catheter end,blood,deep vein catheter,middle urinary,pleural effusion and peripherally inserted central catheter (PICC).The detectable rate of gram-negative bacteria,gram-positive bacteria,fungi and viruses was 46.43％ (78 strains),29.76％ (50 strains),18.45％ (31 strains),and 5.36％ (9 strains) respectively.Infection occurred mainly within 1 month after surgery,accounting for about 80.36％ (135 strains),especially at 1st week after surgery,accounting for about 34.52％ (58 strains).Gram-positive bacteria had a higher drug resistance rate,including penicillins,macrolides,aminoglycosides,quinolones,linamides,etc.especially in the highest rate of Enterococcus faeciurr.Gram-negative bacteria were individualized based on the different strains of the bacteria,and they were relatively low in the resistance of the carbapene.Conclusion Infection is one of the most common complications after liver transplantation.To reduce the incidence of infection after liver transplantation,efforts should be made to shorten the duration of operation and ICU stay time,improve the basic nutritional status of recipients,and enhance monitoring of the recipient's infection after liver transplantation,to further increase the survival rate of postoperative liver transplantation recipients and improve the quality of life.
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The present study was designed to establish a multi-wavelength quantitative fingerprinting method for San-Huang Tablets (SHT), a widely used and commercially available herbal preparation, where high performance liquid chromatography (HPLC) with a diode array detector (DAD) was employed to obtain the fingerprint profiles. A simple linear quantitative fingerprint method (SLQFM) coupled with multi-ingredient simultaneous determination was developed to evaluate the quality consistency of the tested samples qualitatively and quantitatively. Additionally, the component-activity relationship between chromatographic fingerprints and total radical-scavenging capacity in vitro (as assessed using the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assay) was investigated by partial least squares regression (PLSR) analysis to predict the antioxidant capacity of new samples from the chromatographic fingerprints and identify the main active constituents that can be used as the target markers for the quality control of SHT. In conclusion, the strategy developed in the present study was effective and reliable, which can be employed for holistic evaluation and accurate discrimination for the quality consistency of SHT preparations and other traditional Chinese medicine (TCM) and herbal preparations as well.