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Jia Fan

Publications and source records attributed to Jia Fan.

At least 19 recordsLinked to original sources

A rapid CRISPR-based nanodroplet assay enables direct clinical identification of mycobacteria species.

The global incidence and mortality of nontuberculous mycobacterial infections have risen sharply with population aging. In some regions, they are now surpassing Mycobacterium tuberculosis complex infections, imposing a substantial clinical and economic burden. Because nontuberous mycobacteria exhibit species-level heterogeneity and require prolonged culture for identification, their diagnosis remains slow and is frequently inaccurate. Here, we describe a multiplexed clustered regularly interspaced short palindromic repeats (CRISPR)-assisted nanodroplet differential identification (CANDI) diagnostic platform that integrates species-agnostic target amplification with species-specific CRISPR-associated protein 12a (Cas12a) detection in fluorescence-barcoded nanodroplets. By spatially compartmentalizing CRISPR reactions into color-encoded nanodroplets, CANDI overcomes the multiplexing limitations of conventional CRISPR diagnostics and enables simultaneous interrogation of multiple mycobacterial targets in a single assay. We designed a 16-plex panel that distinguishes 15 clinically relevant Mycobacterium species and subspecies. CANDI achieved high analytical sensitivity and accurate discrimination in samples containing coinfections with multiple species or subspecies. When applied to 230 clinical specimens, including sputum, tracheal aspirates, and other respiratory fluids, CANDI delivered subspecies-level results within 3.5 hours, achieving 97.08% sensitivity and 99.7% specificity relative to culture-based identification. By combining multiplexed, high-specificity CRISPR detection with scalable droplet-based engineering, CANDI has the potential to overcome the culture dependency of current diagnostics and enable species- and subspecies-level identification across the genetically complex Mycobacterium genus, offering a clinically adaptable framework for rapid, precision diagnosis of mycobacterial infections.

Humans↗

Durvalumab and tremelimumab, with or without lenvatinib, combined with transarterial chemoembolisation in participants with embolisation-eligible hepatocellular carcinoma (EMERALD-3): a global, randomised, open-label, sponsor-blinded, phase 3 study.

BACKGROUND: Transarterial chemoembolisation (TACE), a standard treatment for embolisation-eligible hepatocellular carcinoma (HCC), induces tumour immune responses. Single tremelimumab regular interval durvalumab (STRIDE) is a standard treatment in advanced HCC. In this phase 3 trial, we assessed the efficacy and safety of STRIDE, with or without lenvatinib, plus TACE, in participants with embolisation-eligible HCC. METHODS: EMERALD-3 is a phase 3, randomised, open-label, sponsor-blinded study, conducted at 177 medical sites in 21 countries. Eligible participants were 18 years or older (aged &#x2265;21 years in Egypt or Singapore) at screening and had confirmed HCC (by imaging or histopathologically from biopsy specimen, surgery, or both) not amenable to curative surgery, curative ablation, or transplantation but amenable to TACE. Participants had Child-Pugh class A liver function, an Eastern Cooperative Oncology Group performance status of 0-1, and at least one measurable target intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours. Participants were randomly allocated in a 1:1:1 ratio to receive STRIDE plus lenvatinib plus TACE, STRIDE plus TACE, or TACE until each group reached its preplanned enrolment target of 175 participants. After the STRIDE plus TACE group reached its enrolment target, randomisation was adjusted to continue in a 1:1 ratio between the STRIDE plus lenvatinib plus TACE group and TACE group until approximately 275 participants were enrolled in each of these two groups. Randomisation used a centrally assigned interactive response technology system, stratified by region, baseline tumour burden, and previous palliative embolisation. In the STRIDE plus lenvatinib plus TACE group, on the first day, participants were given 300 mg tremelimumab intravenously, followed by 1500 mg durvalumab plus oral lenvatinib (8 mg for <60 kg bodyweight or 12 mg for &#x2265;60 kg bodyweight); participants then received 1500 mg durvalumab every 4 weeks plus once-daily lenvatinib for up to 36 cycles. In the STRIDE plus TACE group, participants were given 300 mg tremelimumab and 1500 mg durvalumab intravenously on the first day, followed by 1500 mg durvalumab every 4 weeks. The technique and number of TACE procedures were at the investigators' discretion, with the first procedure administered at least 7 days after the first dose of durvalumab in the two investigation treatment groups and within 7 days of random allocation in the TACE group. The primary endpoint was progression-free survival for STRIDE plus lenvatinib plus TACE versus TACE. Key secondary endpoints were overall survival for STRIDE plus lenvatinib plus TACE versus TACE and progression-free survival and overall survival for STRIDE plus TACE versus TACE. This study was registered with ClinicalTrials.gov (NCT05301842), with enrolment completed. FINDINGS: From March 28, 2022, to Nov 20, 2024, 1124 participants were screened. The full analysis set comprised 760 participants, who were randomly allocated to STRIDE plus lenvatinib plus TACE (n=293), STRIDE plus TACE (n=175), or TACE (n=292). 633 (83%) participants were male and 127 (17%) were female; 548 (72%) were Asian. At the first data cutoff (Sept 2, 2025); the overall median follow-up for progression-free survival was 10&#xb7;0 months (IQR 4&#xb7;6-17&#xb7;2); median follow-up for progression-free survival was 11&#xb7;0 months (IQR 4&#xb7;8-18&#xb7;4) for STRIDE plus lenvatinib plus TACE and 8&#xb7;3 months (4&#xb7;1-15&#xb7;5) for TACE. Median progression-free survival was 13&#xb7;0 months (95% CI 12&#xb7;2-16&#xb7;7) for STRIDE plus lenvatinib plus TACE versus 9&#xb7;8 months (8&#xb7;0-11&#xb7;4) for TACE (HR 0&#xb7;70 [95% CI 0&#xb7;57-0&#xb7;86]; p=0&#xb7;0007). At the second data cutoff (Feb 23, 2026) and a median follow-up for overall survival of 24&#xb7;6 months (IQR 16&#xb7;5-31&#xb7;5) for STRIDE plus lenvatinib plus TACE and 22&#xb7;9 months (14&#xb7;9-30&#xb7;2) for TACE, median overall survival was 39&#xb7;5 months (95% CI 34&#xb7;1-not reached) for STRIDE plus lenvatinib plus TACE and 34&#xb7;7 months (28&#xb7;8-not reached) for TACE (HR 0&#xb7;84 [95% CI 0&#xb7;65-1&#xb7;09]; p=0&#xb7;18). At this data cutoff, median progression-free survival was 12&#xb7;9 months (95% CI 10&#xb7;2-15&#xb7;9) for STRIDE plus TACE and 8&#xb7;1 months (6&#xb7;5-10&#xb7;2) for the first 175 participants randomised to TACE (HR 0&#xb7;71 [95% CI 0&#xb7;56-0&#xb7;91]), with median follow-up of 10&#xb7;3 months (IQR 4&#xb7;6-23&#xb7;7) for STRIDE plus TACE and 7&#xb7;7 months (3&#xb7;0-18&#xb7;5) for the first 175 participants randomly allocated to TACE. The most common adverse events of maximum grade 3 or 4 were hypertension (34 [12%] of 287) for STRIDE plus lenvatinib plus TACE, post-embolisation syndrome and anaemia (ten [6%] of 175 each) for STRIDE plus TACE, and post-embolisation (17 [6%] of 290) for TACE. 184 (64%) participants receiving STRIDE plus lenvatinib plus TACE, 89 (51%) receiving STRIDE plus TACE, and 68 (23%) receiving TACE had serious adverse events. Treatment-related adverse events with an outcome of death during the treatment-emergent period occurred in seven (2%) of 287 participants who received STRIDE plus lenvatinib plus TACE (two for myocarditis; and one each for hepatic failure, haemophagocytic lymphohistiocytosis, septic shock, cardiac failure, and unknown cause), none of 175 participants who received STRIDE plus TACE, and two (1%) of 290 participants who received TACE (one each for acute myocardial infarction and unknown cause). INTERPRETATION: STRIDE plus lenvatinib plus TACE showed a statistically significant progression-free survival improvement versus TACE. These findings support a STRIDE-based regimen as a potential new treatment option for people with embolisation-eligible HCC; additional follow-up is being conducted for final analysis of overall survival across treatment groups. FUNDING: AstraZeneca.

Adult↗

Development of Cre-dependent retrograde trans-multisynaptic tracer based on pseudorabies virus bartha strain.

Mapping the neural circuit of a specific neuronal subclass is central to understanding the working mechanism of the brain. Currently, numerous types of transgenic mice expressing Cre recombinase have been engineered and widely used in neuroscience. To map the multilevel inputs into the neural circuit of a specific neuronal subpopulation, a Cre-dependent retrograde trans-multisynaptic tracer must be developed. The vaccine strain of Pseudorabies virus (PRV, Bartha strain) can infect neurons and spread in a retrograde manner in the neural circuit. In this study, we engineered the genome of PRV Bartha strain to prepare two new tracers, PRV676 and PRV829, by replacing the TK gene of PRV with the Cre-dependent expression cassette of the fluorescent protein gene and the TK gene. These two tracers can separately and Cre-dependently express EGFP and mRuby3 and produce progeny viruses in vitro and in vivo, which can help to map the multilevel inputs of a specific neuronal subpopulation expressing Cre. Collectively, our work provides two new tools for neuroscience research.

Herpesvirus 1, Suid↗

LRP4 mutations promote tumor progression and resistance to anti-PD-1 therapy in recurrent hepatocellular carcinoma.

BACKGROUND AND AIMS: HCC recurrence is a major factor limiting long-term survival and the cause of most deaths in patients with HCC. However, molecular characterization and potential therapeutic targets of recurrent HCC remain mostly unknown. APPROACH AND RESULTS: We performed whole-exome sequencing in 63 matched primary and recurrent HCC tumors and combined the data with whole-genome sequencing results in 43 paired samples from our previous study. Sanger sequencing was used to identify all low-density lipoprotein receptor-related protein 4 ( LRP4 ) coding exons in 203 additional patients with recurrent HCC. We identified LRP4 somatic mutations in 7.8% (24/309) of recurrent tumors and only 0.97% (3/309) of primary tumors ( p <0.001). Prognosis after the second liver resection was poorer in patients with an LRP4 mutation. Biofunctional investigations demonstrated that inactivating LRP4 mutations promoted tumor progression and immunosuppression. Mechanistically, mutated LRP4 reduced intratumoral conventional type 1 dendritic cell and CD8 + T cell infiltration by repressing C-C motif chemokine ligand 4 expression and secretion through activation of &#x3b2;-catenin signaling, resulting in resistance to anti-programmed cell death protein-1 therapy. Patients with recurrent HCC carrying an LRP4 mutation did not benefit from anti-programmed cell death protein-1 treatment after their second resection surgery. A &#x3b2;-catenin inhibitor-reversed LRP4-induced resistance to anti-programmed cell death protein-1 therapy in humanized tumor-bearing mice. CONCLUSIONS: Our results identified novel LRP4 mutations important in recurrent HCC. Inactivating LRP4 mutations were associated with resistance to anti-programmed cell death protein-1 therapy and could be useful biomarkers for precision therapy in patients with recurrent HCC.

Humans↗

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.

Aged↗

Utilizing generalized autocalibrating partial parallel acquisition (GRAPPA) to achieve high-resolution contrast-enhanced MR angiography of hepatic artery: initial experience in orthotopic liver transplantation candidates.

OBJECTIVE: To evaluate feasibility of using GRAPPA to acquire high-resolution 3D contrast-enhanced MR angiography (CE-MRA) of hepatic artery and value of GRAPPA for displaying vessels anatomy. MATERIALS AND METHODS: High-resolution CE-MRA using GRAPPA was performed in 67 orthotopic liver transplantation recipient candidates. Signal intensity (SI) and relative SI, i.e., Cv-ro (vessel-to-liver contrast) of the aorta and the hepatic common artery (HCA), were measured. The SI and the relative SI were compared and analyzed using T-test. For purpose of qualitative evaluation, the vessel visualization quality and the order of depicted hepatic artery branches were evaluated by two radiologists independently and assessed by weighted kappa analysis. The depiction of hepatic arterial anatomy and variations was evaluated, and results were correlated with the findings in surgery. RESULTS: The mean SI values were 283.29+/-65.07 (mean+/-S.D.) for aorta and 283.16+/-64.07 for HCA, respectively. The mean relative SI values were 0.698+/-0.09 for aorta and 0.696+/-0.09 for HCA, respectively. Homogeneous enhancement between aorta and HCA was confirmed by statistically insignificant differences (p-values were 0.89 for mean SI values and 0.12 for mean relative SI values, respectively). The average score for vessel visualization ranged from good to excellent for different artery segments. Overall interobserver agreement in the visualization of different artery segments was excellent (kappa value>0.80). The distal intrahepatic segmental arteries were well delineated for majority of patients with excellent interobserver agreement. Normal hepatic arterial anatomy was correctly demonstrated in 53 patients, and arterial anomalies were accurately detected on high-resolution MRA image of all 14 patients. CONCLUSION: High-resolution hepatic artery MRA acquired using GRAPPA in a reproducible manner excellently depicts and delineates small vessels and can be routinely used for evaluating OLT candidates.

Adult↗

Bid-independent mitochondrial activation in tumor necrosis factor alpha-induced apoptosis and liver injury.

The death receptor apoptosis pathway is intimately connected with the mitochondrial apoptosis pathway. Bid is a BH3-only pro-death Bcl-2 family protein and is the major molecule linking the two pathways. Bid-mediated mitochondrial activation occurs early and is responsible for the prompt progress of tumor necrosis factor alpha (TNF-alpha)-induced apoptosis. However, in both cultured cells and animal models of TNF-alpha-induced injury, later-phase Bid-independent mitochondrial activation could be demonstrated. Consequently, bid-deficient mice are still susceptible to endotoxin-induced liver injury and mortality. Notably, embryonic hepatocyte apoptosis and lethality caused by TNF-alpha in the absence of p65relA cannot be rescued by the simultaneous deletion of bid. Further studies indicate that multiple mechanisms including reactive oxygen species, JNK, and permeability transition are critically involved in Bid-independent mitochondrial activation. Inhibition of these events suppresses TNF-alpha-induced mitochondrial activation and apoptosis in bid-deficient cells. These findings thus indicate that there are at least two sets of mechanisms of mitochondrial activation upon TNF-alpha stimulation. While the Bid-mediated mechanism is rapid and potent, the Bid-independent mechanism progresses gradually and involves multiple players. The critical involvement of Bid-independent mitochondrial activation in TNF-alpha-induced apoptosis demands the intervention of TNF-alpha-mediated tissue injury via multiple avenues.

Animals↗

Polyethylene glycol fractionation improved detection of low-abundant proteins by two-dimensional electrophoresis analysis of plant proteome.

Poor detection of low-abundant proteins is a common problem in two-dimensional electrophoresis (2-DE) for separation of proteins in a proteome analysis. This is attributed partially, at least, to the existence of high-abundant proteins, e.g. ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) in plants. They engage a large proportion of the whole-cell proteins and thus prevent low-abundant proteins from being up-taken by immobilized pH gradient (IPG) strip, consequently making the latter poorly detectable by 2-DE. In this work, we report a straightforward protocol for preparation of whole-cell proteins through differential polyethylene glycol (PEG) precipitation aiming at elimination of Rubisco from plant protein samples. In comparison with 2-DE analysis of protein samples prepared using a conventional TCA/acetone method, a relatively high reproducibility of proteins was achieved using a PEG fractionation protocol in terms of protein yield and protein species. As expected, the large subunit of Rubisco was precipitated predominantly in the 16% PEG fraction. This allowed proteins of the Rubisco-containing fraction to be analyzed separately from those of other PEG fractions. After taking into account the overlapping protein spots among 2-DE gels of all fractions through image and statistical analyses, we detected with this protocol a total 5077 protein spots, among which ca. 80% are proteins undetectable with the TCA/acetone method, while the rest of proteins exhibited a significant increase in their abundance. This protocol was developed using Arabidopsis as a source of protein and thus may also be applicable to protein preparations of other plants.

Arabidopsis↗

[Inhibition of growth and metastasis of hepatocellular carcinoma by rapamycin: experiment with mice].

OBJECTIVE: To investigate the effects of rapamycin (RPM) in inhibiting the growth and metastasis of hepatocellular carcinoma (HCC). METHODS: Human HCC cells of the line MHCC97H with a high potential of metastasis were divided into 3 groups to be cultured with cyclosporine A (CsA) 100 ng/ml, RPM 10 ng/ml, or CsA + RPM for 48 hours. Flow cytometry was used to examine the apoptosis and cell cycle MTT method was used to examine the effect of RMP on the proliferation of the MHCC97H cells. RT-PCR was used to detect the mRNA expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hypoxia-inducible factor-1alpha (HIF-1alpha), and transforming growth factor b (TGFb). Another MHCC97H cells were cultured in complete medium without RPM for 48 hours, then the protein expression of VEGF in the supernatant was detected by ELISA. Twenty-eight nude LCI-D20 mice were inoculated with human HCC cells and then divided into 4 groups to be fed with CsA (25 mg/kg), RPM (2 mg/kg), CsA + RPM, and normal saline (0.2 ml, as control group) for 35 days. Then the mice were killed to take the weight of inoculated tumor, measure the blood drug concentration, calculate the lung metastasis rate and number of metastatic foci, and observe pathology of the lung. RESULTS: CsA showed no effect on the cycle of the MHCC97H cells. The MHCC97H cells of the RPM and CsA + RPM groups arrested at the stage G(0)/G(1) (both P = 0.000). MMT method also showed that the proliferation of the MHCC97H cells in the RPM and CsA + RPM groups were blocked (P = 0.003 and P = 0.002). However, CsA did not influence the proliferation of the MHCC97H cells. Flow cytometry showed that RPM did not promote the apoptosis of the MHCC97H cells. RT-PCR showed that RPM down-regulated the mRNA expression of VEGF and HIF-1alpha (both P < 0.05), however, did not influence the mRNA expression of bFGF, TGFb, and TGFb. The VEGF protein level in the supernatant of the culture fluid of MHCC97H cells of the RPM group was (890.3 +/- 25.1) pg/ml, significantly lower than that of the control group, (1583.7 +/- 17.3) pg/ml (P = 0.000). The tumor inhibiting rate of the RPM group was 63.7%, not significantly different from that of the RPM + CsA group (80.9%, P = 1.000). The metastatic rate of the CsA and control groups were both 100% with a higher number of metastatic tumors in the CsA group (P = 0.046). CONCLUSION: RPM significantly inhibits the growth and metastasis of HCC. RPM-based immunosuppressive regimen may be of value in HCC patients receiving liver transplantation.

Animals↗

Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma: Report of an initial experience.

AIM: To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune, rapamycin) in a consecutive cohort of 248 liver allograft recipients. METHODS: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL-based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation (OLT) were divided into group A (n = 11), those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B (n = 18), and those who developed renal insufficiency caused by calcineurin inhibitor (CNI) were assigned to group C (n = 7) after OLT. RESULTS: The patients were followed up for a median of 10.4 mo (range, 3.8-19.1 mo) after conversion to SRL therapy and 12.3 mo (range, 5.1-34.4 mo) after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% (12/18) patients (2 with progressive tumor, 7 with stable tumor and 3 without tumor) were still alive due to conversing to SRL and/or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia (n = 2), anemia (n = 8), and oral aphthous ulcers (n = 7) found in our cohort were easily manageable. CONCLUSION: The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.

Adaptor Proteins, Signal Transducing↗

[Indication of liver transplantation for hepatocellular carcinoma: Shanghai Fudan Criteria].

OBJECTIVE: To evaluate the effects of different selection criteria on the prognosis of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) and to explore the new criteria adapted for Chinese National Situation. METHODS: A retrospective analysis was performed on 251 consecutive patients with HCC who underwent LT between April 2001 and January 2006 at our institution. We compared the outcome of the patients meeting different criteria such as milan, UCSF and the Pittsburgh modified TNM criteria. Survival rates were calculated using the Kaplan-Meier method, and differences between the curves were assessed by log-rank test. RESULTS: There was no significant difference in 1, 2, 3-year survival rates and recurrence-free survival rates between milan criteria (n = 93; 86%, 77%, 77% and 91%, 86%, 86%) and UCSF criteria (n = 131; 90%, 83%, 83% and 92%, 89%, 89%). According to Pittsburgh criteria (n = 207), the 1, 2, 3-year survival rates and recurrence-free survival rates were 84%, 74%, 67% and 85%, 83%, 73%, respectively. For advanced tumors (over all the criteria), the survival rates and recurrence-free survival rates decreased significantly (n = 44; 65%, 43%, 43% and 47%, 43%, 43% respectively). When criteria (named as Shanghai Fudan Criteria) were expanded to HCC patients with solitary lesions < or = 9 cm in diameter, or no more than 3 lesions, the largest < or = 5 cm, with a total tumor diameter < or = 9 cm, there was no significant difference in 1, 2, 3-year survival rates and recurrence-free survival rates (n = 151; 88%, 80%, 80% and 90%, 88%, 88%, respectively) as compared with milan criteria, but more patients using Shanghai Fudan Criteria could undergo liver transplantation. CONCLUSION: Shanghai Fudan Criteria, which expanded the tumor size limits, does not adversely impact survival of HCC patients after LT.

Adult↗

[Analysis of the risk factors influencing the prognosis of orthotopic liver transplantation for hepatocellular carcinoma and summary of relevant clinical experience].

OBJECTIVE: To analyze the risk factors influencing the prognosis of orthotopic liver transplantation for hepatocellular carcinoma (HCC) and sum up the relevant clinical experience in diagnosis and treatment of HCC. METHODS: The clinical data of 198 HCC patients, 177 males and 21 females, aged 49 (24-83), were analyzed. RESULTS: The 0.5-, 1-, and 2-year survival rates were 89%, 78%, and 65 respectively. The rates of disease-free survival (DFS) were 85%, 73, and 67% respectively. Univariate analysis revealed that tumor size, presence of vascular invasion, Edmondson grade, TNM classification, and preoperative alpha-fetoprotein (AFP) were significantly related to DFS, and the 4 foregoing factors were also related to the survival rate. Cox regression analysis suggested that presence of vascular invasion was an independent prognostic factor of survival rate and DFS. CONCLUSION: Vascular invasion plays a leading role in evaluating the prognosis of orthotopic liver transplantation for HCC. It is important to discover the micro-metastasis and explore more effective approaches to prevent recurrence after transplantation.

Adult↗

Study of severe and rare complications of transarterial chemoembolization (TACE) for liver cancer.

OBJECTIVE: To study severe and rare complications of transarterial chemoembolization (TACE) for liver cancer. METHODS: Clinical records of severe and rare complications following TACE in 1348 cases of liver cancer from January 1997 to February 2004 were studied retrospectively. RESULTS: A total of 2012 TACE procedures were performed for 1348 patients. There were 3 cases of spontaneous rupture of liver cancer, 1 case of perforation of duodenum, 3 cases of liver abscess (1 of them was associated with sepsis), 1 case of pulmonary embolism, 1 case of spasm of the hepatic artery, 40 cases of hepatic artery occlusion, 3 cases of femoral nerve injury, 1 case of bilioma and 1 case of acute renal failure. CONCLUSION: Although the severe complications of TACE are rare, the procedure should be done cautiously including super selection of hepatic artery, slow infusion of lipiodol, careful postoperative observations and early detection and management of complications.

Antineoplastic Agents↗

[The effects of different clinicopathologic variables on serum protein fingerprint in hepatocellular carcinoma patients].

OBJECTIVE: To investigate the effects of different clinicopathologic variables on serum protein fingerprint in hepatocellular carcinoma (HCC) patients. METHODS: Serum samples were collected from 112 HCC patients, Special serum protein or peptide spectra was determined by surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) measurement after treating the sample onto weak cation exchange (WCX2) protein chip for each case. The serum protein profiles were compared by BioMarker Wizard Software among the patients stratified according to gender, AFP, presence of portal vein tumor thrombus (PVTT), tumor size, tumor number, presence of cirrhosis, respectively. RESULTS: According to serum protein fingerprints of 112 HCC patients, a total of 100 protein peaks were identified at the m/z value ranging from 1100 to 30,000. (1) Sixteen significant differential proteins were found between the groups of HCC with single tumor and those with multiple tumors (P < 0.01). (2) Only one significant differential protein was found between the groups of HCC with tumor size > 3 cm and those with tumor size 5 cm and those with tumor size 10 cm and those with tumor size <or= 10 cm (P < 0.01). (3) Sixteen significant differential proteins were found between the groups of macroscopic portal vein tumor thrombus (Ma-PVTT) and those without PVTT (N-PVTT); Only 2 significant differential protein were found between the groups of microscopic portal vein tumor thrombus (Mi-PVTT) and N-PVTT (P < 0.01); eight significant differential proteins were found between the groups of Ma-PVTT and Mi-PVTT (P < 0.01). (4) No significant differential protein was found when patients stratified according to gender, presence of cirrhosis and AFP. CONCLUSIONS: PVTT, tumor number and tumor size had significant effects on serum protein fingerprint, while no significant effect on serum protein from gender, presence of cirrhosis and AFP. The most profound impact on the serum protein was attained when cutoff was chosen to be presence of Ma-PVTT compared to less effect from Mi-PVTT and 5cm for tumor size.

Adult↗

Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial.

BACKGROUND/AIMS: Recurrence after resection of hepatocellular carcinoma (HCC) is a frequent event. This study evaluated the effect of postoperative interferon alpha (IFN alpha) treatment on recurrence and survival in patients with hepatitis B virus (HBV)-related HCC. METHOD: Two hundred and thirty six patients were randomized after resection into IFN alpha treatment (5 micro i.m. tiw for 18 months) and control groups. Treatment was terminated if recurrence was diagnosed, and recurrence was managed the same way in both groups. Statistical analysis was based on the method of intent-to-treat. RESULTS: The two groups were comparable in all clinicopathological parameters. The median overall survival was 63.8 months in the treatment group and 38.8 months in the control group (P=0.0003); the median disease-free survival period was 31.2 versus 17.7 months (P=0.142). Fever, leucocytopenia, and thrombocytopenia were adverse effects in the treatment group, but were mostly manageable. CONCLUSIONS: IFN alpha treatment improved the overall survival of patients with HBV-related HCC after curative resection, probably by postponing recurrence.

Analysis of Variance↗

Dendritic cell infiltration and prognosis of human hepatocellular carcinoma.

AIM: To elucidate the relationship between local immunocompetent cells and prognosis of human hepatocellular carcinoma (HCC) after resection. METHODS: HE staining and immunohistochemical study were carried out on specimens from patients underwent surgical resection. Local immunocompetent cells, such as dendritic cells (DCs), memory T cells, CD3+ T lymphocytes and CD8+ T lymphocytes, were counted and their relationships with tumor-free survival rate were analyzed by grouping DCs with the T lymphocytes retrospectively. RESULTS: The number grade of infiltrating immunocompetent cells in HCC nodules and pericancerous tissues under HE staining had no significant correlation with tumor-free survival time (P=0.054, 0.071, respectively). DCs were mainly among tumor cells, encircling tumor cells with their pseudopodia and were in contact with T lymphocytes. A certain number of DCs in HCC nodules (> or =25/10HPF) statistically correlated to tumor-free survival time (P=0.005), while a certain number of DCs in pericancerous tissues (> or =28/10HPF) had no correlation with tumor-free survival time (P=0.329). The number of memory T cells, CD3+ T lymphocytes and CD8+ T lymphocytes in HCC nodules strongly correlated to tumor-free survival time (P=0.003, 0.005, 0.037, respectively). The tumor-free survival rate curves revealed that the more DCs or together with memory T cells/CD3+ T lymphocytes or that the more CD8+ T lymphocytes were detected in HCC nodules, the better the prognosis would be. CONCLUSIONS: Marked infiltration of DCs in HCC nodules was closely related to the prognosis of HCC after surgical resection and can be served as a predictive index for recurrence and metastasis of HCC.

Adolescent↗

Abdominal drainage was unnecessary after hepatectomy using the conventional clamp crushing technique.

A prophylactic abdominal drainage catheter is routinely inserted by many surgeons in patients after hepatic resection. Between January 2002 and September 2004, 462 consecutive patients who had undergone hepatic resection using a clamp crushing method by the same surgical team were retrospectively divided into the drainage group (n = 357) and the nondrainage group (n = 105). There was no difference in hospital mortality between the two groups of patients (drainage group, 0.6% vs. nondrainage group, 0%; P = 1.0). However, there was a greater incidence of surgical complications in the drainage group (31.4% vs. 8.6%, P < 0.001), and greater incidence of wound complications and subphrenic complications in the drainage group compared to the nondrainage group (24.4% vs. 4.8%, P < 0.001). In addition, the mean (+/- SEM) postoperative hospital stay of the drainage group was 13 +/- 6.5 days, which was significantly longer than that of the nondrainage group (9.7 +/- 3.3 days, P = 0.001). On multivariate analysis, abdominal drainage and intraoperative bleeding were the independent risk factors that were significantly associated with the incidence of drainage-related complications. The results suggested that routine abdominal drainage is unnecessary after hepatic resection when the conventional clamp crushing method is used during parenchyma transection.

Abdomen↗

Solitary fibrous tumor of the liver.

BACKGROUND: Solitary fibrous tumor of the liver is a rare neoplasm. So far, 23 cases have been described in the English literature. We reported an additional case. METHODS: A 46-year-old woman presented with abdominal mass for 2 weeks. Both abdominal sonography and CT scan showed a solid mass occupying the right lobe of the liver. Right lobectomy was performed and the tumor was resected. RESULTS: Pathological examination showed spindle cell and fibroblast-like cells within the collagenous troma. On immunohistochemical staining, these spindle tumor cells showed diffusely CD34 positive reactivity. The post-operative course was uneventful. The patient recovered smoothly, and was alive half a year without evidence of disease recurrence. CONCLUSIONS: The proper diagnosis was depended on CD34 immunohistochemical study. The number of solitary fibrous tumor of the liver reported to date is too limited to confirm the definite prognosis of the tumor.

Adult↗