Pregnancy and the disease recurrence of patients previously treated for differentiated thyroid cancer: A systematic review and meta analysis.

BACKGROUND: Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC. METHODS: We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies. RESULTS: A total of ten studies were included. The sample size ranged from 8 to 235, with participants' age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals [CI]: 0.06-0.25; I2 : 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy ( Ptrend <0.05). The pooled risk of recurrence in the pregnancy group showed no evidence of a significant difference from that in the nonpregnancy group (OR: 0.75; 95% CI: 0.45-1.23; I2 : 0). The difference in follow-up time (below/above five years) was not associated with either the proportion of recurrence in all pregnant patients ( P >0.05) or the OR of recurrence in studies with a comparison group ( P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 [95% CI: 0.14-1.87; I2 : 59%]). CONCLUSION: In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022367896.

Pregnancy and Progression of Differentiated Thyroid Cancer: A Propensity Score-Matched Retrospective Cohort Study.

CONTEXT AND OBJECTIVE: Differentiated thyroid cancer (DTC) is very common in women of reproductive age. However, it remains unclear whether pregnancy is associated with DTC progression before surgical treatment. METHODS: This retrospective cohort study, conducted at the Peking University Third Hospital in Beijing, China between January 2012 and December 2022, included 311 eligible women aged 20 to 45 years. To control for potential confounders, we first used propensity score matching (PSM) to match the pregnant group (n = 48) with the nonpregnant group (n = 154) on age, tumor size, tumor type, and Hashimoto's thyroiditis status at baseline, and then used Cox proportional risk models stratified by the matched pairs to estimate the association of pregnancy with DTC progression. RESULTS: After PSM, the pregnant and nonpregnant groups were well comparable at baseline (standardized difference < 10% and P > .05). Over an average observation period of 2.5 years, we observed no difference between the pregnant group and the matched nonpregnant group in DTC progression-free survival (hazard ratio [HR] = 0.96; 95% CI, 0.56 to 1.65; P = .895), tumor enlargement-free survival (HR = 0.99; 95% CI, 0.56 to 1.76; P = .969) or lymph node metastasis-free survival (LNM) (HR = 0.67; 95% CI, 0.21 to 2.13; P = .498). The postoperative pathological characteristics also showed no significant difference between the pregnant and nonpregnant groups (P > .05). CONCLUSION: Pregnancy seemed to be irrelevant to DTC progression-free survival before surgical treatment. Further prospective cohort studies are needed to translate this finding into clinical practice.

The Association of Pregnancy with Disease Progression in Patients Previously Treated for Differentiated Thyroid Cancer: A Propensity Score-Matched Retrospective Cohort Study.

Background: Differentiated thyroid cancer (DTC) is increasingly common in women of reproductive age. However, whether pregnancy increases the risk of DTC progression/recurrence after treatment remains controversial. The study aimed to assess the association of pregnancy with risk of progression in patients previously treated for DTC. Methods: This was a retrospective cohort study following 123 pregnant women and 1376 nonpregnant women at Peking University Third Hospital after initial treatment for DTC between January 2012 and December 2022. To control the effect of confounding, we carefully matched pregnancy (n = 107) and nonpregnancy groups (n = 298) in terms of baseline characteristics by using propensity score matching (PSM). Results: At baseline, the pregnancy and nonpregnancy groups were balanced in all matched variables. At follow-up, the percentage of DTC progression in the two groups was 12 (11.8%) and 47 (15.8%), respectively. Regression models showed no evidence of association of pregnancy with the risk of progression (odds ratio: 0.74 and 95% confidence interval: 0.37-1.50; p = 0.404), and remained consistent across long/short follow-up and other subgroup variables. We found that the shorter the time interval between treatment and pregnancy, the higher the risk of DTC progression (ptrend = 0.019). Conclusions: The risk of DTC progression in pregnant women was not higher than that in the well-matched, nonpregnant women. For young women previously treated for DTC, disease progression might not be a concern for their future pregnancy plan, but it seems safer to wait at least 1 year before pregnancy compared with immediate pregnancy.

[Analysis and management of the biliary complications after liver transplantations].

OBJECTIVE: To discuss the relevant factors of biliary complications after liver transplantation and to investigate the value of comprehensive management for the complications. METHODS: The data of 366 patients undergoing liver transplantation from October 2000 to March 2012 was analyzed retrospectively, and the risk factors were analyzed by univariate analysis and Stepwise Logistic regression. The cases with biliary leak were administered thorough drainage. The cases with anastomotic biliary stricture were administered sacculus dilatation through percutaneous transhepatic cholangiography (PTC) and endoscopicretrograde cholangiopancreatography (ERCP). If necessary, some cases were placed biliary tract brackets. The patients with nonanastomotic biliary stricture were treated with PTC plus choledochoscope. RESULTS: All the 366 patients were followed up for 58.5 (10 to 129) months. Biliary complications after liver transplantation were diagnosed in 42 cases among these patients. The incidence for biliary complications was 11.5%. The univariate analysis and multivariate Logistic regression analysis showed that the second warm ischemia period and the blood loss and the damage of blood supply and the diameter of biliary anastmosis were significantly associated with biliary complications after liver transplantations (Wald = 9.474 to 17.208, P < 0.05). Twelve cases with biliary leak were cured through abdominal and nasobiliary drainage. Twenty-two cases with anastomotic biliary stricture were administered sacculus dilatation through ERCP or PTC and were cured, including 6 cases were placed biliary tract brackets. Among 8 cases with nonanastomotic biliary stricture, 6 cases were cured through PTC associating with choledochoscope. One case was treated second liver transplantation and another case got worse. CONCLUSIONS: Ischemic injury and the diameter of anastmosis are risk factors for biliary complications after liver transplantations. The interventional management of biliary stricture and bile leakage after liver transplantation is safe and effective.

HBV recurrence lowered by lamivudine/HBIG combination therapy in liver transplant patients: ten-year experience.

BACKGROUND: Lamivudine and hepatitis B immunoglobulin (HBIG) are widely used to treat patients with hepatitis B recurrence after liver transplantation. However, the outcomes are inconclusive. The present study was undertaken to evaluate the effect of combined therapy on patients with hepatitis B recurrence after liver transplantation. METHODS: Twenty-two patients with hepatitis B recurrence after liver transplantation from August 2000 to October 2011 were enrolled in this study. Of these patients, 16 received lamivudine plus HBIG (combination therapy group) and 6 were treated with lamivudine alone (lamivudine-treated group). The clinical features were matched in the two groups. HBV recurrence parameters, HBsAg clearance rate, patient survival rate, and survival time were compared. RESULTS: The average time of follow-up was 47.2 months (range 13-99). Significant difference was noted in the HBsAg clearance rate in the lamivudine-treated and combination therapy groups (50% vs 93.8%, P<0.05). There was no significant difference in the time of HBV recurrence, patient survival rate and survival time between lamivudine-treated and combination therapy groups (P>0.05). CONCLUSION: Compared with lamivudine monotherapy, combination therapy significantly increased the HBsAg clearance rate in patients with HBV recurrence after liver transplantation.

Newly designed Y-configured single-catheter stenting for the treatment of hilar-type nonanastomotic biliary strictures after orthotopic liver transplantation.

PURPOSE: This study was designed to introduce our novel technique of percutaneous single catheter placement into the hilar bile ducts strictures while fulfilling the purpose of bilateral biliary drainage and stenting. We investigated the efficacy and safety of the technique for the treatment of hilar nonanastomotic biliary strictures. METHODS: Ten patients who were post-orthotopic liver transplantation between July 2000 and July 2010 were enrolled in this study. Percutaneous Y-configured single-catheter stenting for bilateral bile ducts combined with balloon dilation was designed as the main treatment approach. Technical success rate, clinical indicators, complications, and recurrent rate were analyzed. RESULTS: Technical success rate was 100%. Nine of the ten patients had biochemical normalization, cholangiographic improvement, and clinical symptoms relief. None of them experienced recurrence in a median follow-up of 26 months after completion of therapy and removal of all catheters. Complications were minor and limited to two patients. The one treatment failure underwent a second liver transplantation but died of multiple system organ failure. CONCLUSIONS: Percutaneous transhepatic Y-configured single-catheter stenting into the hilar bile ducts is technically feasible. The preliminary trial of this technique combined with traditional PTCD or choledochoscopy for the treatment of hilar biliary strictures after orthotopic liver transplantation appeared to be effective and safe. Yet, further investigation is needed.

[The influential factors and clinical significance of acute renal failure complicated to orthotopic liver transplantation].

OBJECTIVE: To analyze the risk factors for acute renal failure (ARF) early after liver transplantation. METHODS: The data of 362 patients undergoing liver transplantation from August 2000 to December 2010 were retrospectively analyzed, including 71 patients with ARF (ARF group) and 291 without ARF (non-ARF group). Thirty-six variables, including clinical and experimental variables, were analyzed by t test for continuous variables and χ(2) test for discrete variables. The variables with significance (P < 0.05) were then analyzed with Stepwise logistic regression. RESULTS: Twelve variables, including pretransplant serum creatinine, hemoglobin, thrombinogen activity, total bilirubin, MELD scores, total operation time, intraoperative blood loss, intraoperative blood transfusion, preoperative urine output, preoperative hepatic encephalopathy, intraoperative low blood pressure and postoperative infection, had significant difference between two groups (F = 10.30 - 182.70, P = 0.000 - 0.041). The Stepwise logistic regression analysis for 12 variables demonstrated that the high level of pretransplant serum creatinine, the low pretransplant thrombinogen activity, the high MELD scores, the large volume of intraoperative blood loss, postoperative infection were the independent risk factors of ARF complicated to orthotopic liver transplantation (P < 0.05). CONCLUSIONS: Early ARF is a key negative factor for the survivors after orthotopic liver transplantation. The reason for ARF complicated to OLT is multiple. The high level of pretransplant serum creatinine, the low pretransplant thrombinogen activity, the high MELD scores, the large volume of intraoperative blood loss, postoperative infection were the independent risk factors of ARF complicated to orthotopic liver transplantation.

[The pathological feature of primary hepatic carcinoma on explanted liver and its significance].

OBJECTIVE: To investigate the pathological feature of primary hepatic carcinoma and the clinical significance. METHODS: From August 2000 to December 2007, there were 89 patients with cirrhosis and carcinoma of liver who accepted whole liver resection. The whole liver was cut into 10 mm slices to examine the tumor size, number, distribution, capsule, satellite nodes, portal vein tumor thrombi (PVTT). The invaded adjacent tissue and lymph nodes were recorded, the distance from satellite to major tumor was measured, then histological examinations were carried out, and the final diagnosis was made by pathologists. RESULTS: The total of 89 cases included hepatocellular carcinoma in 86 cases and cholangiocarcinoma in 3 cases; 53 cases with multiple tumors and 36 cases with solitary tumor; complete capsule only in 14 cases, no obvious margin in 11 cases, 13 cases had a major tumor in the right lobe and a small tumor in the left lobe; 8 of 25 cases with gross invaded tissue were confirmed by histological examination, 7 of 16 cases with swollen lymph nodes were infiltrated by cancer cells. There were 47 cases with PVTT (47.2%) and 39 cases with satellite nodes (43.8%). PVTT and satellite nodes increased with the increase of sizes and the numbers of the tumors. The distance from satellite node to major tumor mostly were 0.5 - 3.0 cm. CONCLUSIONS: The whole explanted liver can completely reflect the characteristics of growth and infiltration of hepatic carcinoma. Attention must be paid to the small cancer lesions in another lobe, distal satellite nodes from major tumor, and tumor thrombi in a small branch of portal vein, which can not be found by imaging, and might influence the curative effectiveness after liver resection or transplantation.

[Clinical values of color doppler ultrasound and magnetic resonance angiography in diagnosis of the tumor emboli and thrombi in portal venous system].

OBJECTIVE: To evaluate the clinical values of color Doppler ultrasound (BUS?) and magnetic resonance angiography (MRA) in diagnosis of the tumor emboli and thrombi in portal venous system. METHODS: Examination of the portal venous system by BUS and MRA was conducted on 165 patients with undergoing liver transplantation because of cirrhosis or primary hepatic carcinoma before the operation. The extrahepatic portal vein was observed during operation and pathological examination was conducted after the operation. The results of BUS and MRA were compared as regards the sensitivity and specificity in discovering the tumor emboli and thrombi in portal venous system. RESULTS: The overall sensitivity, specificity, and positive predictive rate of BUS for the portal vein embolus were 86.5%, 97.4%, and 85.3% respectively. The overall sensitivity, specificity, and positive predictive rate of MRA for the portal vein embolus were 90.5%, 99.3%, and 95.7% respectively. However the accuracy in diagnosing the nature of the portal venous embolus was less than 70% for these 2 methods. CONCLUSION: Non-invasive, both BUS and MRA help discover the portal vein embolus. However, false positivity and false negativity still exist. And both fail to diagnose the nature of the portal venous embolus.

[Adjuvant chemotherapy after orthotopic liver transplantation for advanced hepatocellular carcinoma].

OBJECTIVE: To investigate the feasibility, reliability and therapeutic effectiveness of adjuvant chemotherapy for advanced hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). METHODS: The clinical data of adjuvant chemotherapy after OLT in 10 advanced HCC patients were studied retrospectively. FAP chemotherapy regimen was adopted calcium folinate (CF) 200 mg/m(2) and 5-Fluorouracil 500 mg/m(2) iv on D1 to D5, and doxorubicin 40 mg/m(2), cisplatin 30 mg/m(2) iv on D1, with 28 days as a cycle. The opportune time of chemotherapy, chemotherapy regimen, synergistic action between cytotoxic agent and immunosuppressive agent on liver and kidney and side-effects were preliminarily evaluated. RESULTS: 7/10 patients are surviving, with the longest survival of 32 months, and the shortest 9 months. Three patients died after operation, two at 13 months, one at 20 months after OLT, all died of metastasis. The incidence of one year survival was 9/9. During the period of chemotherapy, the side-effects of adjuvant chemotherapy were moderate. CONCLUSION: Chemotherapy which is able to prolong the life-span of patients with advanced HCC after orthotopic liver transplantation is feasible and effective, the side-effects were mild. The choice of opportune time of chemotherapy might influence the outcome.

[Effective evaluation of liver transplantation for hepatocellular carcinoma].

OBJECTIVE: To evaluate the effect of liver transplantation for hepatocellular carcinoma and to explore the suitable indication for liver transplantation for advanced primary hepatocellular carcinoma. METHOD: Clinical data were collected and studied with 43 patients with cirrhosis who had unresectable hepatocellular carcinoma and who underwent liver transplantation from August, 2000 to December, 2003. All the survived patients were followed up. RESULTS: The longest following period was 45 months. 18 patients died by the end of the April, 2004. The 1-year survival rate was 85.5%, the 2-year survival rate 65.5%, the 3-year survival rate was 43.0%. CONCLUSION: In our country, some advanced primary hepatocellular carcinoma without extrahepatic metastasis is still indicated for liver transplantation. Some patients could have the opportunity to survive relatively long time.

A report of 28 cases of 3-year follow-up after liver transplantation for advanced hepatocellular carcinoma.

AIM: To investigate the therapeutic value of liver transplantation for advanced hepatocellular carcinoma (HCC). METHODS: Twenty-eight patients with advanced HCC were treated by liver transplantation from August 2000 to October 2003 at Peking University Third hospital. All the patients were followed up to evaluate the result. RESULTS: The longest follow-up duration was 3 years and 3 mo. Till the end of the follow-up period, 17 patients had already died and 11 were alive. Of those who died, 10 patients died of tumor recurrence, 4 died during the perioperative period, 2 died of variceal bleeding, and 1 died of biliary complication. According to life table method, the 1-, 2-, and 3-year survival rates were 87.5%, 52.5%,and 42.9%, respectively. CONCLUSION: Liver transplantation provides a new treatment under the circumstance of lacking of an effective treatment for advanced HCC at present. Some patients can survive for a relatively long time free of tumor. In our country, if the patients can afford liver transplantation, advanced HCC without extrahepatic metastasis is an indication for liver transplantation at present.

Prevention and treatment of hepatitis B recurrence after liver transplantation.

OBJECTIVE: To study the efficacy of liver transplantation on end-stage hepatitis B related liver diseases, and the prevention and treatment strategies of hepatitis B recurrence after the transplantation. METHODS: The efficacy of combined treatment of lamivudine and hepatitis B immune globulin (HBIG) therapy on 24 patients who had received liver transplantation was retrospectively studied. RESULTS: All the 24 patients with end-stage hepatitis B-related liver diseases treated with lamivudine alone or combined therapy of lamivudine and HBIG showed normal liver function and 21 of them lost hepatitis B virus (HBV) markers. However, the remaining 3 patients became HBsAg positive again soon after liver transplantation. CONCLUSIONS: Liver transplantation is effective for patients with end-stage hepatitis B-related liver diseases. Combined treatment of lamivudine and HBIG may prevent the recurrence of hepatitis B after the operation.

[Analysis of the correlated factors of the early mortality after orthotopic liver transplantation].

OBJECTIVE: To investigate the correlated factors of early mortality after orthotopic liver transplantation. METHODS: The preoperative liver function, coagulative status, the graft's warm and cold ischemia times and the details of the operations of 42 patients were summarized retrospectively and the comparison between survival and death patients performed to analyse the correlated factors of early death after orthotopic liver transplantation. RESULTS: Thirteen of the 42 patients died early after the transplantation. Two died of vascular complication and two fo graft primary nonfunction. The comparison between those without identified causes (9 patients, in death group) and survivors (29 patients, in survival group) showed that the patients in death group had a poorer preoperative liver function and coagulative status than those in survival group, the blood loss was more than that in survival group, the length of time of operation, the duration of hypotension and anhepatic time were also longer than those in survival group. CONCLUSION: The poorer preoperative liver function, and especially the coagulative status were the main causes of early mortality after orthotopic liver transplantation, the vascular complications and the graft primary nonfunction were the other reasons that led to some patients' deaths.

[Liver transplantation for advanced primary hepatocellular carcinoma].

OBJECTIVE: To investigate the value of liver transplantation for late hepatocellular carcinoma. METHODS: Thirty-six patients were treated by liver transplantation from August 2000 to February 2002, of which 15 patients had had advanced hepatocellular carcinoma and thirteen of these 15 patients were evaluated for results. RESULTS: The 1-year survival rate was 86% (6/7). Only one patient died of recurrence within 6 months. The tumor-free survival was 5 to 19 months. Till February 2002, two patients have survived for 10 months and 19 months with recurrence. CONCLUSION: In our country, if the patients can afford liver transplantation, advanced hepatocellular carcinoma without extrahepatic metastasis is still indicated for liver transplantation, since some patients may survive relatively long.