Objective:To investigate the influence of cytochrome P450 2A6 (CYP2A6) gene polymorphisms on liver function injury in patients with hyperthyroidism treated with methimazole.Methods:The study selected 90 patients with hyperthyroidism who were treated with methimazole in the Department of Thyroid Surgery at the First Affiliated Hospital of Zhengzhou University from Sept. 2023 to Aug. 2024 as the research subjects. Based on the occurrence of liver injury, they were divided into a liver injury group ( n=36) and a non-liver injury group (n=54). Peripheral blood DNA was extracted from the patients, and the CYP2A6 gene genotypes (rs8192725, rs8192720, and rs28399433) were detected using the polymerase chain reaction (PCR) amplification method. The association between CYP2A6 gene polymorphisms and liver injury induced by methimazole treatment in hyperthyroidism was analyzed. Results:The comparison of genotype distribution frequencies at the rs8192725 locus between the liver injury group and the non-liver injury group showed a statistically significant difference ( P<0.05). The AG and GG genotypes at the rs8192725 locus were protective factors against liver injury in patients with hyperthyroidism (AG vs. AA, OR: 0.21; 95% CI: 0.08-0.57; P<0.05; GG vs. AA, OR: 0.24; 95% CI: 0.06-0.89; P<0.05; AG+GG vs. AA, OR: 0.22; 95% CI: 0.09-0.54; P<0.05). The frequency of the G allele of rs8192725 in the liver injury group was significantly lower than that in the non-liver injury group (G vs. A, OR: 0.36; 95% CI: 0.19-0.70; P<0.05), indicating that it is a protective factor for liver injury in hyperthyroid patients receiving methimazole treatment. Conclusions:The CYP2A6 gene polymorphism at the rs8192725 locus is associated with the occurrence of liver injury in patients with hyperthyroidism treated with methimazole. The G allele may be a protective factor against liver injury in patients with hyperthyroidism, suggesting that individualized treatment plans can be developed based on the patient's genotype.

Objective:To investigate the influence of cytochrome P450 2A6 (CYP2A6) gene polymorphisms on liver function injury in patients with hyperthyroidism treated with methimazole.Methods:The study selected 90 patients with hyperthyroidism who were treated with methimazole in the Department of Thyroid Surgery at the First Affiliated Hospital of Zhengzhou University from Sept. 2023 to Aug. 2024 as the research subjects. Based on the occurrence of liver injury, they were divided into a liver injury group ( n=36) and a non-liver injury group (n=54). Peripheral blood DNA was extracted from the patients, and the CYP2A6 gene genotypes (rs8192725, rs8192720, and rs28399433) were detected using the polymerase chain reaction (PCR) amplification method. The association between CYP2A6 gene polymorphisms and liver injury induced by methimazole treatment in hyperthyroidism was analyzed. Results:The comparison of genotype distribution frequencies at the rs8192725 locus between the liver injury group and the non-liver injury group showed a statistically significant difference ( P<0.05). The AG and GG genotypes at the rs8192725 locus were protective factors against liver injury in patients with hyperthyroidism (AG vs. AA, OR: 0.21; 95% CI: 0.08-0.57; P<0.05; GG vs. AA, OR: 0.24; 95% CI: 0.06-0.89; P<0.05; AG+GG vs. AA, OR: 0.22; 95% CI: 0.09-0.54; P<0.05). The frequency of the G allele of rs8192725 in the liver injury group was significantly lower than that in the non-liver injury group (G vs. A, OR: 0.36; 95% CI: 0.19-0.70; P<0.05), indicating that it is a protective factor for liver injury in hyperthyroid patients receiving methimazole treatment. Conclusions:The CYP2A6 gene polymorphism at the rs8192725 locus is associated with the occurrence of liver injury in patients with hyperthyroidism treated with methimazole. The G allele may be a protective factor against liver injury in patients with hyperthyroidism, suggesting that individualized treatment plans can be developed based on the patient's genotype.

Objective:To study the risk factors of very early recurrence (VER, within 3 months) after R 0 resection of hepatocellular carcinoma (HCC), and to establish a predictive model. Methods:Of 427 HCC patients [with 368 males, 59 females, aged (52.7±12.1) years] who developed early recurrence (within 2 years) after R 0 resection from January to December 2008 at Zhongshan Hospital, Fudan University were enrolled in the test cohort. Another 590 patients [with 525 males, 65 females, aged (54.7±11.0) years] who underwent R 0 resection from January to June 2009 were enrolled in the validation cohort. Risk factors were investigated and a predictive model was established. Results:In the test cohort, 126 patients (29.5%) developed VER and their survival outcomes were extremely poor. Serum α-fetoprotein (AFP) level >827 μg/L, multiple tumors, microvascular invasion (MVI) and tumor number were independent risk factors for VER. A new predictive model (0.809·AFP+ 1.262·tumor number+ 0.983·MVI) was established by logistic regression in predicting VER after surgery. The receiver operating characteristic curve showed that the area under the curve (AUC) in predicting VER was 0.722 (95% CI: 0.669-0.774, P<0.001). In the validation cohort, the AUC of this model was 0.785 (95% CI: 0.715-0.855, P<0.001). Conclusions:A high AFP level, multiple tumors, and MVI were independent risk factors for VER of HCC after R 0 resection. The prediction model consisting of these three factors demonstrated robustness and it has the potential in clinical application.

Objective:To study the safety and treatment outcomes of portal vein embolization (PVE) combined with lenvatinib plus an anti-programmed death-1(PD-1) antibody to treat patients with initially unreasectable hepatocellular carcinoma (uHCC).Methods:This study retrospectively analyzed the data of six patients with uHCC who received first-line combined systemic therapy with lenvatinib plus an anti-PD-1 antibody, and then underwent pre-hepatectomy PVE at the Department of Liver Surgery at Zhongshan Hospital, Fudan University from May 2019 to November 2020. All enrolled patients were males, aged (54.6±6.2) (ranged 46 to 63) years. Tumor response and liver volume were evaluated by medical imagings once every 2 months (±2 weeks) and evaluated using the Response Evaluation Criteria in Solid Tumours (version 1.1). Patients were followed-up by outpatient interviews or by phone calls to record their survival and tumor outcome status.Results:Three of the six enrolled patients had Barcelona Clinic Liver Cancer stage A and three had stage B disease. One patient achieved a partial response and five patients had stable diseases. The mean ± s. d. future liver remnant (FLR) percentage was (29.0±8.9) % before PVE and the combination therapy, and was (41.3±10.8) % before the last evaluation for liver surgery ( t=10.79, P<0.001). Hepatectomy was carried out in five patients, and one patient who failed to develop significant FLR hypertrophy did not undergo hepatectomy. Grade B post-hepatectomy liver failure and major postoperative complications (i.e. pleural effusion requiring additional percutaneous drainage) occurred in one patient. After a median post-operative follow-up of 4.5 (range: 1.0-12.3) months, all five patients were alive and were tumor free. Conclusion:PVE followed by hepatectomy is feasible in a uHCC patients receiving systemic therapy with lenvatinib and an anti-PD-1 antibody.

Objective:To investigate the clinical efficacy of the combination therapy of lenvatinib and programmed death-1 (PD-1) antibodies in unresectable or advanced hepatocellular carcinoma (HCC).Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of 59 patients with unresectable or advanced HCC who were admitted to Zhongshan Hospital of Fudan University from September 2018 to January 2020 were collected. There were 54 males and 5 females, aged from 25 to 73 years, with a median age of 52 years. All 59 patients underwent combination therapy with lenvatinib and PD-1 antibodies including 43 cases undergoing first-line therapy and 16 cases who cannot tolerate first-line therapy or with tumor progressed after first-line therapy undergoing second-line therapy. Observation indicators: (1) clinical efficacy; (2) adverse drug reactions and treatment; (3) follow-up and survival. Follow-up was performed using outpatient examination or telephone interview to detect tumor diameter of the target lesion, overall survival and progression free survival of patients up to December 2020. Measurement data with skewed distribution were expressed as M ( P25,P75) or M (range). Count data were represented as absolute numbers and (or) percentages. The Kaplan-Meier method was used to calculate the median duration of response (DoR), median overall survival time, median progression free survival time, survival rates and draw survival curves. Results:(1) Clinical efficacy: the objective response rate (ORR), complete response rate (CR), partial response rate (PR), stable disease rate (SD), progression disease rate (PD), time to response (TTR) and median DoR of 59 HCC patients were 37.3%(22/59), 11.9%(7/59), 25.4%(15/59), 37.3%(22/59), 25.4%(15/59), 2.6 months(2.1 months, 4.0 months), 6.3 months[95% confidence interval ( CI) as 2.2 to 10.5 months], respectively. The ORR, CR, PR, SD, PD and TTR of 43 HCC patients undergoing first-line therapy were 41.9%(18/43), 16.3%(7/43), 25.6%(11/43), 37.2%(16/43),20.9%(9/43), 2.2 months(2.0 months, 3.5 months), respectively. The median DoR of 43 patients undergoing first-line therapy was not reached. The ORR, CR, PR, SD, PD, TTR and median DoR of 16 HCC patients undergoing second-line therapy were 4/16, 0, 4/16, 6/16, 6/16, 3.8 months (3.6 months, 4.1 months), 4.2 months(95% CI as 2.0 to 6.3 months), respectively. Six of 59 HCC patients underwent R 0 resection due to tumor converting to resectable HCC with the conversion and resection rate of 10.2%(6/59). Among the 6 patients, 5 cases undergoing first-line treatment had the conversion and resection rates of 11.6% (5/43) and 1 case undergoing second-line treatment had the conversion and resection rates of 1/16, respectively. (2) Adverse drug reactions and treatment: 25 of 59 HCC patients underwent 3 to 4 grade adverse drug reactions with the incidence of 42.4%(25/59). Among the 25 patients, 10 cases including 5 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of gamma glutamyltransferase >5×upper limit of normal (ULN), 9 cases including 4 cases undergoing first-line therapy and 5 cases undergoing second-line therapy had the level of aspartate aminotransferase >5×ULN, 5 cases including 4 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred gastrointestinal hemorrhage, 4 cases undergoing first-line therapy had the level of white blood cell count <2.0×10 9/L, 4 cases including 1 case undergoing first-line therapy and 3 cases under-going second-line therapy had the level of total bilirubin >3×ULN, 3 cases undergoing first-line therapy had the level of neutrophil count <1.0×10 9/L, 3 cases including 2 cases undergoing first-line therapy and 1 case undergoing second-line therapy occurred ascites, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy had the level of platelet count <50.0×10 9/L, 2 cases undergoing first-line therapy had the level of alanine aminotransferase >5×ULN, 2 cases undergoing first-line therapy occurred hyponatremia, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred pulmonary infection, 2 cases including 1 case undergoing first-line therapy and 1 case undergoing second-line therapy occurred type 1 diabetes, 1 case undergoing first-line therapy occurred hypokalemia, 1 case undergoing first-line therapy occurred myocarditis, 1 case undergoing first-line therapy occurred hypophysistis, 1 case undergoing first-line therapy occurred bullous dermatitis, 1 case undergoing first-line therapy occurred hypertension. Three of 59 HCC patients underwent 5 grade adverse drug reactions ,with the incidence of 5.1%(3/59), including 1 case undergoing first-line therapy with immune hepatitis, 1 case undergoing second-line therapy with immune pneumonia and 1 case undergoing second-line therapy with immune enteritis. Some of patients underwent multiple adverse drug reactions at the same time. Twenty five patients undergoing 3 to 4 grade adverse drug reactions were relieved with the treatment of drug reduction, drug withdrawal, symptomatic treatment or hormone therapy. Three patients undergoing 5 grade adverse drug reactions died after being treated with high-dose hormone shock and hepatoprotective treatment. (3) Follow-up and survival: all 59 patients were followed up for 1.5 to 25.2 months, with a median follow-up time of 13.3 months. Of them, patients undergoing first-line therapy were followed up for 1.9 to 25.2 months, with a median follow-up time of 13.5 months. During follow-up,20 cases undergoing first-line therapy died with the fatality rate of 46.5%(20/43). Patients undergoing second-line therapy were followed up for 1.5 to 24.4 months, with a median follow-up time of 10.8 months. During follow-up, 10 cases undergoing second-line therapy died with the fatality rate of 10/16. Up to the latest follow-up, the tumor diameter of the target lesion in all 59 patients, in patients undergoing first-line therapy and in patients undergoing second-line therapy was 75 mm(38 mm, 125 mm), 74 mm(36 mm, 116 mm), 84 mm(48 mm,150 mm), respectively. The ratio of tumor diameter of the target lesion at latest follow-up to tumor diameter of the target lesion at baseline were -9.05%(-27.3%, 19.7%), -16.1%(-28.8%, 13.6%), 13.2%(-24.7%, 23.5%) for all 59 patients, patients undergoing first-line therapy and patients undergoing second-line therapy, respectively. The median overall survival time and median progression free survival time of patients undergoing first-line therapy and patients undergoing second-line therapy were 17.1 months(95% CI as 11.0 to 23.2 months), 10.8 months(95% CI as 5.0 to 16.6 months) and 10.8 months(95% CI as 9.2 to 12.4 months), 3.0 months(95% CI as 1.6 to 4.4 months), respectively. Conclusion:For unresectable or advanced HCC, combination therapy with lenvatinib and PD-1 antibodies can obtain effective antitumor activity and less incidence of adverse drug reactions.

Objective To study the clinical impact of microvascular invasion (MVI) on patients with intrahepatic cholangiocarcinoma (ICC) after R0 resections.Methods The clinicopathological data of 359 patients with ICC who underwent R0 resection in the Zhongshan Hospital,Fudan University between January 2000 and December 2008 were retrospectively studied.Univariate analysis and multivariate analysis were carried out to study factors related to postoperative survival outcomes and recurrence.The impact of MVI on patients with ICC after R0 resection was studied.Results The incidence of MVI was 13.6％ in the study cohort.MVI was correlated with HBV infection (P ＜ 0.05),liver cirrhosis (P ＜ 0.05) and tumor differentiation (P ＜ 0.05).The 1-,3-,5-year overall survival (OS) between the MVI positive and negative groups were 50.0％,20.9％,12.2％ and 63.9％,33.1％,22.0％ respectively (P ＜ 0.05),and the median survival time was 13 months and 18.5 months (P ＜0.05).The 1-,3-,5-year recurrence free survival (RFS) rates between the MVI positive and negative groups were 29.7％,12.7％,8.5％ and 50.6％,26.9％,18.4％,respectively (P ＜0.05),and the median recurrence free survival time was 8 months and 12.5 months (P ＜ 0.05).Multivariate analysis showed that MVI was an independent risk factor affecting recurrence after R0 resection (HR 1.852,95％ CI:1.075 ～ 3.195,P ＜ 0.05).Conclusions The occurrence of MVI in ICC patients was associated with hepatitis B infection.MVI was an independent risk factor affecting recurrence in ICC patients after R0 resection.However,it was not an independent risk factor of overall survival in patients after R0 resection.The clinical impact of MVI on patients with ICC was not as strong as for hepatocellular carcinoma.

ObjectiveTo study the clinicopathologic features of post-transplant lymphoproliferative disorders (PTLD).Methods Three cases of PTLD in renal transplant recipients were studied.The clinical data,diagnosis and differential diagnosis,and relevant literatures were also reviewed.Results All the 3 cases studied had received cyclosporine A or Tac after transplantation.The duration between organ transplantation and diagnosis of PTLD was 10 years,4 years and 2 months respectively.Two cases were suffered from monomorphic PTLD and 1 from plasmacytic hyperplasialike PTLD in morphology.Two cases of monomorphic PTLD died within one year after diagnosis.Conclusion PTLD is a lymphoproliferative disease with distinctive morphologic and clinical characteristics.The main treatments included the dosage reduction of immunosuppressive agents,radiotherapy and chemotherapy.The prognosis of monomorphic PTLD was poor.

Objective To investigate the effects of fast-track surgery on postoperative rehabilitation of patients with liver cancer. Methods Forty-one patients with liver cancer who had been admitted to Zhongshan Hospital of Fudan University from 9 to 30 in July 2008 were randomly divided into fast-track surgery group (n =20) and routine treatment group (n =21) according to the random number table. Patients in fast-track surgery group were preoperatively educated in order to lessen their anxiety. Bowel preparation was not applied before operation, and they were orally administered with 1000 ml of enteral nutrition emulsion (1300 kcal), then they were fasted for 4 hours before operation. Urethral catheter and gastric tube were removed after operation. They were orally administered with 1000 ml of enteral nutrition emulsion on postoperative day 2, and were encouraged to partake in off-bed activity shortly after the operation. The off-bed time, anus exhaust time, postoperative complica-tions, hospitalization time, expense, nutritional and metabolic indexes on postoperative day 1, 3 and 5, hepatic and renal function, immune and stress indexes between the 2 groups were compared by t test and chi-square test. Results There were significant differences in off-bed time, anus exhaust time, patients' weight, expense, total bilirubin level on postoperative day 1, 3 and 5, and level of serum TNF-α on postoperative day 3 between the 2 groups (t =7.065, 5.483, 3.754, 2.291,2.289, 3.218, 3.192, 2.434, 2.089, P <0.05). Conclusions Fast-track surgery can accelerate the postoperative rehabilitation of patients with liver cancer.

Objective To investigate the diagnosis and treatment of hepatic metastasis from gastrointestinal stromal turnor(GIST).Methods The clinical data of 16 patients with GIST who had been admitted to our hospitalfrom December 1993 to May 2007 were retrospectively analyzed.Results Of all patients,14 underwent radical resection and 2 underwent palliative operation.Two patients with palliative operation and 3 with radical resection were administered with imatinib postoperatively. All patients were followed up for 3-161 months,and GIST metastasis and invasion was observed in 8 of the 14 patients who received radical resection.Of the 7 patients with hepatic metastasis.3 were treated with hepatic artery chemoembolization,1 was administered with imatinib,2 received reoperation and 1 did not receive any treatment. Reoperation was carried out on 1 patient who had abdominal wall metastasis.The 1-and 3-year survival rates of the 16 patients were 92%and 74%,respectively.Conclusions The recurrence rate of GIST after hepatectomy is high.Complete surgical resection is the best curative treatment for hepatic metastasis from GIST and GIST recurrence.The combination of surgical resection and imatinib administration may help to improve the prognosis of patients with hepatic metastasis from GIST.

Objective To evaluate the diagnosis and treatment of focal nodular!hyperplasia of the liver (FNH). Methods Retrospective analysis was made on 60 FNH cases in terms of clinical findings, images, pathologic examination and surgical treatment. Results Of the 60 FNH patients in our hospital from 1993 to 2003, 41 were male and 19 female. The average age was 37 year′s old. Fifty-five cases had single focus, the other five were of multiple lesion, with tumor diameter 10cm in one. Correct preoperative diagnosis was made in 33 cases (55%). The correct diagnostic rate of BUS, CT and MRI was 33.3%, 58.3% and 72.0%, respectively. All 60 cases underwent operation with an uneventful recovery and without recurrence at follow-up. ConclusionsCT and MRI are mandatory for the diagnosis of FNH. Definite preoperative diagnosis is usually difficult even in cases of typical type of FNH. Surgical resection is the treatment of choice when a patient becomes symptomatic or when malignancy could not be excluded.