Abstract Background: Therapeutics targeting PD-(L)1 have demonstrated impressive clinical activity in several type of cancers. However, only a small proportion of patients develop long-term response and resistance frequently occurs. LAG-3 and TIM-3 are inhibitory immune checkpoints frequently upregulated and co-expressed with PD-1 on tumor-infiltrating T cells, contributing to T cell dysfunction. Thus, we hypothesized that simultaneously targeting PD-1/LAG-3/TIM-3 would further restore T cell response and the triple combination of Tislelizumab (Tisle, anti-PD-1), LBL-007 (anti-LAG-3) and Surzebiclimab (Surze, anti-TIM-3) would provide greater clinical benefit.Methods: To evaluate the rationale and the anti-tumor activity of triple combination, LAG-3 and TIM-3 expression were analyzed in in vitro T cells, syngeneic mouse models and cancer patients with anti-PD-(L)1 therapy. The effects of dual blockade of PD-1/LAG-3, PD-1/TIM-3 and the triple blockade of PD-1/LAG-3/TIM-3 on T cell function were evaluated in in vitro activated PBMCs and the anti-tumor efficacy were evaluated in syngeneic mouse models. Relevant gene expression and immune signatures were ranked across 31 solid tumor types in TCGA.Results: Both LAG-3 and TIM-3 expression on T cells were upregulated by anti-PD-1 treatment in syngeneic mouse tumors, similar trend was observed in cancer patients with anti-PD-(L)1 therapy. Dual combination of Tisle/LBL-007 or Tisle/Surze enhanced IFNγ production in in vitro activated human T cells. The dual blockade of PD-1/LAG-3 or PD-1/TIM-3 significantly enhanced tumor growth inhibition compared with anti-PD-1 monotherapy in syngeneic mouse models. The triple combination of Tisle/LBL-007/Surze further enhanced IFNγ production in in vitro activated T cells. In a mouse MC38 colon carcinoma model, the triple blockade of PD-1/LAG-3/TIM-3 demonstrated enhanced anti-tumor activity compared with either dual combination, evidenced by trend of increased tumor growth inhibition and higher tumor-free incidence rate. Finally, the responsiveness of PD-1/LAG-3/TIM-3 triple combination was predicted using 5 signatures, including early effector T cell signature, inflamed signature, LAG-3, TIM-3 and PD-L1 expression. The in silico analyses indicated strong potential in clinical utility such as squamous cell carcinoma of the head and neck (HNSCC).Conclusions: The concurrent blockade of PD-1/LAG-3/TIM-3 represents a promising strategy to enhance T cell function and anti-tumor activity. The results demonstrated the therapeutic potential of the triple combination. A Ph2 study evaluating Tisle in combination with LBL-007 and/or Surze in first-line treatment of recurrent or metastatic HNSCC (NCT05909904) is recruiting. Citation Format: Hengrui Zhu, Jinhui Zhang, Han Yan, Xiao Ding, Juan Yang, Yu Jiang, Minjuan Deng, Haoxuan Song, Fangfang Ping, Fuyun Sun, Xiaoyu Li, Lijie Zhang, Bin Jiang, Weiwei Song, Zhirong Shen, Wei Jin, Jiyuan Zhang, Yun Zhang. Translational assessment of triple combination with Tislelizumab (anti-PD-1), LBL-007 (anti-LAG-3) and < for Surzebiclimab (anti-TIM-3) highlights its strong anti-tumor activity and < for clinical potential in solid tumors such as HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4041.

Introduction Large granular lymphocytic leukemia (LGLL) is a rare chronic lymphoproliferative disorder characterized by persistent clonal expansions of lymphocytes over an extended period in which nearly 80% of cases are T-cell large granular lymphocytic leukemia (T-LGLL) (Alaggio et al. 2022). The clinical and biological features of T-LGLL exhibit significant heterogeneity as it can manifest as either CD8+ or CD4+. Furthermore, T-LGLL is associated with the rearrangement of the T cell receptor (TCR), which can be categorized into αβ T-LGLL and γδ T-LGLL variants. Additionally, few studies have compared αβ T-LGLL and γδ T-LGLL displaying that γδ T-LGLL revealed a similar or more aggressive clinical manifestation than αβ T-LGLL (Bourgault-Rouxel et al. 2008; Sandberg et al. 2006; Barilà et al. 2020; Barila et al. 2023). Thus, in this study, we described the clinical and biological features of 56 γδ T-LGLL patients, comparing to 306 αβ T-LGLL patients from a single institute. Methods A total of 362 patients with a diagnosis of T-LGLL between July 2005 and July 2022 from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science. All the patients met the recommended diagnostic criteria for LGLL(Lamy, Moignet, and Loughran 2017). We conducted a retrospective analysis of patients' clinical data, laboratory examinations, treatment, and follow-up. Non-normal distribution data were expressed as a median and range. Comparisons of continuous variables in different subgroups were analyzed with the Mann-Whitney U test. A χ2 or Fisher exact test was used to compare categorical variables. OS and PFS was calculated using the Kaplan-Meier method and compared by the log-rank test. P value < 0.05 was considered significant. Follow-up was to death or all statistical analyses were performed using the statistical software SPSS 27. Results Out of the 362 consecutive patients identified with T-LGLL, 56 (7.5%) were γδ T-LGLL, while 306 (92.5%) were αβ T-LGLL. Overall, clinical findings were very similar between the two groups in terms of median age (55 vs 54, P = 0.536), sex ratio (1.2 vs 1.3, P = 0.543), severity of neutropenia [absolute neutrophil count (ANC) ≤ 1.5×109 /L: 53.5% vs 53.3%, P = 0.959], anemia [hemoglobin (HB) ≤ 120 g/L: 85.7% vs 79.4%, P = 0.275], thrombocytopenia [Platelet (PLT) ≤ 100×109 /L: 14.3% vs 15.4%, P = 0.837], splenomegaly (32.7% vs 37.6%, P = 0.497), and pure red blood cell aplastic anemia (32.1% vs 39.9%, P = 0.275). Additionally, no significant differences were found between γδ and αβ T-LGLL cases in the frequency of STAT3 mutation (54.2% vs. 39.1%, P = 0.168). However, CD4-/CD8- immunophenotype was more frequent in the γδ T-LGLL cohort compared to αβ T-LGLL (25% vs. 17.6%; P < 0.001). Among the 362 patients, 309 patients (85.3%) required treatment. About 50% of patients received cyclosporine (CsA) and nearly 30% of patients had methotrexate (MTX) in both groups. Our analysis revealed that the overall response rate (ORR) of CsA was higher in the γδ T-LGLL subtype compared to the αβ T-LGLL (ORR: 78.6% vs. 58.7%, P = 0.048), when no significant difference in ORR of MTX was found (ORR: 78.5% vs. 85.2%, P = 0.684). After a median follow-up of 48.8 months for γδ T-LGLL and 53.1 months for αβ T-LGLL, the median overall survival (OS) was not reached in either subtype. There was no difference in median OS between γδ T-LGLL and αβ T-LGLL (152.5 vs. 158.4 months, P = 0.525). Hb ≤ 90g/L, PLT ≤ 150×10^9/L, and the co-existence of other malignancies were associated with decreased OS by univariate analysis in 362 T-LGLL patients. Conclusion In conclusion, patients with γδ T-LGLL exhibited comparable clinical and biological characteristics to those with αβ T-LGLL subtypes. Both subtypes had similar response to CsA or MTX-based therapy. No statistically significant differences in OS were observed between the two subtypes. It is advisable to employ identical therapeutic strategies for the treatment of both γδ T-LGLL and αβ T-LGLL in future clinical practice.

Abstract Aim To establish a clinically applicable organoid-based model for drug sensitivity and evaluate its predictive accuracy in determining the effectiveness of chemotherapy for secondary liver cancer arising from gastrointestinal tumors. Methods Relevant information and tumor tissue from four cases of colorectal cancer with liver metastasis (synchronous or metachronous), and a case of gastric cancer with liver metastasis, were collected at the Seventh Affiliated Hospital of Sun Yat-sen University between January 1, 2019, to December 31, 2022. Liver metastasis organoid models were established, and drug sensitivity tests for fluorouracil, oxaliplatin, and irinotecan were conducted. Drug sensitivity of liver metastatic organoids was assessed using IC50 values. Changes in tumor size in patients before and after clinical drug administration were calculated based on RECIST 1.1 criteria. The relationship between drug sensitivity scores of organoids and tumor size before and after treatment was analyzed. Results Four colorectal cancer liver metastases and one gastric cancer liver metastases were successfully cultured from patient samples. Histological staining verified the homogeneity of these models. Consistency was observed between the drug sensitivity scores of the organoids and the changes in tumor size in patients before and after clinical drug administration. Conclusion The organoid model drug sensitivity testing of secondary liver cancer originating from gastrointestinal tumors can effectively predict the efficacy of chemotherapy drugs in clinical practice and guide treatment decisions.

Abstract Background The most part of primary liver cancer is hepatocellular carcinoma having a poor prognosis. The treatment strategies including multitarget inhibitors, ICIs, and new options are being explored. Recently studies demonstrated the synergistic effect of anti-angiogenesis-targeted drugs combined with immunotherapy. In this study, we explored toripalimab combined with anlotinib as second-line therapy to evaluate the safety and efficacy in advanced hepatocellular carcinoma (HCC). Patients and methods: Twenty-six patients diagnosed with HCC and experienced disease progression or drug intolerance after first-line targeted therapy were included in this study. All enrolled patients received toripalimab combined with anlotinib. The primary endpoint of this study was the objective response rate (ORR), secondary endpoints were progression-free survival (PFS), overall survival (OS), and disease control rates (DCR). Results Finally 22 patients met the protocol were included in the data analysis. The ORR was 7.69%, the mPFS was 3.12 months, mOS was 10.89 months, and DCR was 42.31%, among which 1 patient achieved CR, 1 patient achieved PR, and 9 patients achieved SD. By the last follow-up, the duration of CR in patients had been more than 2 years. No treatment-related deaths occurred, generally this combination therapy is well tolerated. Conclusion In patients who experience disease progression with first-line sorafenib or lenvatinib, toripalimab combined with anlotinib may be a good choice for second-line treatment and is well tolerated. TP53 mutations may serve as biomarkers for this treatment and larger sample size is required for further confirmation.

Long non-coding RNAs (lncRNA) have an essential role in progression and chemoresistance of hepatocellular carcinoma (HCC). In-depth study of specific regulatory mechanisms is of great value in providing potential therapeutic targets. The present study aimed to explore the regulatory functions and mechanisms of lncRNA TINCR in HCC progression and oxaliplatin response. The expression of TINCR in HCC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation, migration, invasion, and chemosensitivity were evaluated by cell counting kit 8 (CCK8), colony formation, transwell, and apoptosis assays. Luciferase reporter assays and RNA pulldown were used to identify the interaction between TINCR and ST6 beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) via miR-195-3p. The corresponding functions were verified in the complementation test and in vivo animal experiment. TINCR was upregulated in HCC and associated with poor patient prognosis. Silencing TINCR inhibited HCC proliferation, migration, invasion, and oxaliplatin resistance while overexpressing TINCR showed opposite above-mentioned functions. Mechanistically, TINCR acted as a competing endogenous (ceRNA) to sponge miR-195-3p, relieving its repression on ST6GAL1, and activated nuclear factor kappa B (NF-κB) signaling. The mouse xenograft experiment further verified that knockdown TINCR attenuated tumor progression and oxaliplatin resistance in vivo. Our finding indicated that there existed a TINCR/miR-195-3p/ST6GAL1/NF-κB signaling regulatory axis that regulated tumor progression and oxaliplatin resistance, which might be exploited for anticancer therapy in HCC.

Background Postoperative delirium (POD) is characterized by acute brain dysfunction, especially in elderly patients. Postoperative pain is an important factor in the development of delirium, and effective pain management can reduce the risk of POD. Thoracic paravertebral block (TPVB) can effectively relieve postoperative pain and inhibit the perioperative stress and inflammatory response. We investigated whether the combination of TPVB with general anesthesia reduced the occurrence of POD following thoracoscopic lobectomy. Methods A total of 338 elderly patients, aged 65–80 years, who underwent elective surgery for video-assisted thoracoscopic lobectomy (VATS) were randomly assigned to either a patient-controlled intravenous analgesia group (PIA) or a patient-controlled paravertebral-block analgesia group (PBA). POD was evaluated using the 3-min diagnostic confusion assessment method (3D-CAM). The postoperative quality of recovery (QoR) was assessed with Chinese version of QoR-40 scale. Pain intensity was measured using the visual analog scale (VAS) score. Tumor necrosis factor-α (TNF-α) and neurofilament light (NFL) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Results Delirium occurred in 47 (28%) of 168 cases in the PIA group and 28 (16.5%) of 170 cases in the PBA group (RR 1.7, p = 0.03). PBA was also associated with a higher rate of overall recovery quality at day 7 after surgery (27.1% vs. 17.3%, P = 0.013) compared with PIA. The incremental change in surgery-induced TNF-α and NFL was greater in the PIA group than PBA group ( p < 0.05). Conclusion Thoracic paravertebral block analgesia is associated with lower incidence of postoperative delirium, probably due to its anti-neuroinflammatory effects. Furthermore, as a component of multimodal analgesia, TPVB provides not only superior analgesic but also opioid-sparing effects. Trial registration The study was registered on the Chinese Clinical Trial Registry Center ( www.chictr.org.cn ; registration number: ChiCTR 2,000,033,238 ) on 25/05/2018.

原发性肝癌作为中国发病率第5位以及致死率第2位的恶性肿瘤,严重威胁着中国人民的生命健康.目前临床仍面临着肝癌的手术切除率较低以及术后复发率过高的难题,寻求有效且可靠的围手术期治疗方案以提高疗效至关重要.近年来,应用FOLFOX方案的肝动脉灌注化疗(HAIC)及其联合治疗显著提高了肿瘤反应率和患者生存率,应用也越来越广泛.近年来的研究显示,将HAIC应用于肝癌手术前的降期转化和术后辅助治疗,在提高手术切除率、降低术后复发风险以及改善患者长期预后等方面起到了积极的作用.该文将对HAIC在肝癌围手术期的临床应用和研究进展进行综述,以期为肝癌围手术期的治疗提供借鉴意义.

原发性肝癌是目前我国第4位常见恶性肿瘤及第2位肿瘤致死病因,严重威胁我国人民的生命和健康.原发性肝癌中>90％的患者为肝细胞癌(以下简称肝癌),手术切除是肝癌患者获得长期生存的最主要治疗手段,然而我国肝癌患者确诊时多为中晚期,初诊可行手术切除的患者仅占15％～30％.对于中晚期不可切除的肝癌,可采取多种治疗手段争取转化为可手术切除,其中FOLFOX方案(奥沙利铂+亚叶酸钙+5-氟尿嘧啶)的肝动脉灌注化疗具有较高的转化切除率和较好的安全性,且操作简单、易于普及.本文以中山大学肿瘤防治中心的经验为基础,结合文献报道,对肝动脉灌注化疗在肝癌转化治疗中的应用作一综述.

Programmed cell death protein-1 (PD-1) inhibitor is recommended to treat advanced hepatocellular carcinoma (HCC). However, the safety of PD-1 inhibitor in patients with high HBV-DNA load is unknown because of the potential risk of hepatitis B virus (HBV) reactivation. This study was to compare the HBV reactivation between patients with low HBV-DNA loads and high HBV-DNA loads undergoing antiviral prophylaxis and PD-1 inhibitor. This was a retrospective study including consecutive hepatitis B surface antigen-positive HCC patients who received PD-1 inhibitor and concurrent antiviral prophylaxis for prevention of clinical hepatitis. Patients were divided into low HBV-DNA group (low group, ≤ 500 IU/ml) and high HBV-DNA group (high group, > 500 IU/ml) according to the baseline HBV-DNA level. The incidences of HBV reactivation, HBV-associated hepatitis, and PD-1 inhibitor disruption were compared between the two groups. Two hundred two eligible patients were included: 94 in the low group and 108 in the high group. Seven patients (5 in the low group and 2 in the high group) developed HBV reactivation, and all recovered from HBV reactivation and HBV-associated hepatitis. The incidence of HBV reactivation in the two groups was low (5.3% vs 1.9%, P = 0.34). There was also no difference in the incidence of HBV-associated hepatitis (P = 0.56), or PD-1 inhibitor disruption (P = 0.82). The multivariable analysis showed PD-1 inhibitor with hepatic arterial infusion chemotherapy was the only significant risk factor for HBV reactivation (P = 0.04) and hepatitis (P = 0.002). With concurrent antiviral prophylaxis, HBV-DNA load higher than 500 IU/ml should not be a contraindication for PD-1 inhibitor.

The lymphocyte-C-reactive protein ratio (LCR) is a recently described inflammation-based score, and it remains unclear which is the optimal inflammation-based score among patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE). A large cohort of HCC patients (n=1625) who underwent TACE as the initial treatment were enrolled in the present study. Inflammation-based scores, including the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), high-sensitivity modified Glasgow Prognostic Score (Hs-mGPS), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and LCR, were all related to the survival of HCC patients, but only the LCR score was a significant and independent predictor in multivariate analysis (hazard ratio: 1.45; 95% confidence interval: 1.27-1.65; P<0.001). Further analysis showed that the LCR score stably and consistently differentiated subgroup patients with distinct prognoses. The predictive accuracies of the LCR score (0.70, 0.68, and 0.68 for 1-, 3-, and 5-year C-index, respectively) were superior to the other inflammatory-based scores (0.60-0.64, 0.58-0.62, and 0.58-0.62 for 1-, 3-, and 5-year C-index, respectively). The LCR score was an independent prognostic indicator for HCC patients who underwent TACE, and it was superior to the other inflammation-based scores in prognostic ability.

BACKGROUND:Gamma-glutamyltransferase (GGT) is involved in tumor development and progression, but its prognostic value in α-fetoprotein- (AFP-) negative (AFP < 25 ng/mL) hepatocellular carcinoma (HCC) patients remains unknown.METHODS:A large cohort of 678 patients with AFP-negative HCC following curative resection who had complete data were enrolled in this study. The optimal cutoff value for the preoperative level of GGT was determined by the X-tile program. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were also identified.RESULTS:The optimal cutoff values for the preoperative levels of GGT were 37.2 U/L and 102.8 U/L, which were used to divide all patients into three subgroups (group 1, GGT < 37.2 U/L (n = 211, 31.1%); group 2, GGT ≥ 37.2 and <102.8 U/L (n = 320, 47.2%); group 3, GGT ≥ 102.8 U/L (n = 147, 21.7%)), with distinct OS times (58.5 vs. 53.5 vs. 44.4 months, P < 0.001) and DFS times (47.9 vs. 40.3 vs. 30.1 months, P < 0.001). Elevated preoperative GGT levels were associated with an unfavorable tumor burden (larger tumor size, multiple tumors, and microvascular invasion) and were selected as independent predictors of a worse OS (group 2 vs. group 1, HR: 1.73 (1.13-2.65), P = 0.011; group 3 vs. group 1, HR: 3.28 (2.10-5.13), P < 0.001) and DFS (group 2 vs. group 1, HR: 1.52 (1.13-2.05), P = 0.006; group 3 vs. group 1, HR: 2.11 (1.49-2.98), P < 0.001) in multivariable analysis.CONCLUSIONS:Elevated preoperative GGT levels are associated with an unfavorable tumor burden and serve as an independent prognostic marker for worse outcomes in AFP-negative HCC patients following resection.

背景与目的 单发肝细胞癌(hepatocellular carcinoma,HCC)合并微血管侵犯(microvascular invasion,MVI)患者根治性切除术后的最佳辅助治疗方案一直存有争议.本试验旨在评估肝切除术后辅助经导管动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)与单纯肝切除术对直径≥5 cm单发HCC合并MVI患者的疗效和安全性.方法 在本随机、开放性、Ⅲ期试验中,将直径≥5 cm单发HCC合并MVI患者随机分为2组(1:1):在肝切除术后接受1–2个周期的辅助TACE治疗(肝切除–TACE组)或单纯接受肝切除(单纯肝切除组).主要终点是无病生存期(disease-free survival,DFS),次要终点包括总生存期(overall survival,OS)和不良事件.结果 在2009年6月1日至2012年12月31日期间,共纳入250例患者,随机分为肝切除–TACE组(n=125)或单纯肝切除组(n=125).两组患者的临床病理特征相似.从随机开始的中位随访时间为37.5个月(四分位距为18.3–48.2个月).肝切除–TACE组的中位DFS显著长于单纯肝切除组[17.45个月(95％置信区间,confidence interval,CI:11.99–29.14)vs.9.27个月(95％CI:6.05–13.70),风险比(hazard ratio,HR)=0.70(95％CI:0.52–0.95),P=0.020].肝切除–TACE组中位OS也显著长于单纯肝切除组[44.29个月(95％CI:25.99–62.58)vs.22.37个月(95％CI:10.84–33.91),HR=0.68(95％CI:0.48–0.97),P=0.029].治疗相关不良事件在肝切除–TACE组中更为多见,虽然这些不良事件一般都是轻度和可控的.两组中最常见的3级或4级不良事件为中性粒细胞减少和肝功能异常.结论 对于直径≥5 cm单发HCC合并MVI患者,根治术后进行辅助TACE治疗是一种合适的选择,且毒性是可接受的.

背景与目的 肝动脉化疗栓塞术(transarterial chemoembolization,TACE)被推荐为巴塞罗那临床肝癌(Barcelona Clinic Liver Cancer,BCLC)A–B期的不可切除肝细胞癌(hepatocellular carcinoma,HCC)的标准治疗方法.然而,TACE对巨大(≥10 cm)A–B期HCC的疗效远不能令人满意,肝动脉灌注化疗(hepatic artery infusion chemotherapy,HAIC)被认为可能是该疾病更好的一线治疗方法.因此,我们比较了使用改良的FOLFOX方案(modified FOLFOX,mFOLFOX)进行HAIC与TACE治疗不可切除的巨块型HCC的安全性和有效性.方法 一项前瞻性非随机II期研究在患有不可切除的巨块型HCC患者中开展.治疗方法为使用mFOLFOX方案每3周进行一次HAIC(奥沙利铂,85 mg/m2动脉灌注;甲酰四氢叶酸,400 mg/m2动脉灌注;氟尿嘧啶,400 mg/m2静脉推注和2400 mg/m2持续静脉滴注),使用50 mg表柔比星、50 mg洛铂、6 mg丝裂霉素和碘油聚乙烯醇颗粒进行TACE.评估了肿瘤反应、肿瘤进展时间(time-to-progression,TTP)和安全性.结果 本研究共招募了79例患者:HAIC组38例,TACE组41例.HAIC组的部分缓解率和疾病控制率均高于TACE组(52.6％vs.9.8％,P<0.001;83.8％vs.52.5％,P=0.004).HAIC和TACE组的中位TTP分别为5.87和3.6个月[风险比(hazard ratio,HR)=2.35,95％置信区间(confidence interval,CI)=1.16–4.76,P=0.015)].HAIC组比TACE组有更多的患者接受了手术切除(10 vs.3,P=0.033).HAIC组中3–4级不良事件(adverse events,AE)和严重不良事件(serious adverse events,SAE)发生数均低于TACE组(3–4级AE:13 vs.27,P=0.007;SAE:6 vs.15,P=0.044).因无法耐受的治疗相关不良事件或撤回知情同意书而导致治疗提前终止的患者在TACE组中多于HAIC组(10 vs.2,P=0.026).结论 与TACE相比,使用mFOLFOX进行HAIC表现出显著优势的治疗反应性和更低的毒性.对于不可切除的巨块型HCC,HAIC可能是一种可行且有前景的一线治疗方法.

Background: Several members of the SIRT family (SIRT1-7), a highly conserved family of NAD+-dependent enzymes, play an important role in tumor formation. Recently, several studies have suggested that SIRT7 is abnormally expressed in several tumor types. However, no studies have assessed its clinical significance in esophageal squamous cell carcinoma (ESCC). Method: We investigated SIRT7 protein expression levels in ESCC and its potential association with selected clinico-pathological parameters and overall survival of 93 ESCC patients by immunohistochemical staining on a tissue microarray. Results: SIRT7 expression was higher in ESCC compared with non-neoplastic tissues (P<0.001). In addition, higher SIRT7 expression levels were observed at the later American Joint Committee on Cancer stage (P = 0.049). In addition, the average survival time of patients with high SIRT7 expression in esophageal tumors was lower than that of patients with low SIRT7 expression, especially in patients with a tumor size larger than 5 cm (P = 0.003). Conclusions: SIRT7 may participatein the development of ESCC and may be a promising target for the diagnosis and treatment of esophageal cancer.

肝细胞癌(肝癌)合并门静脉癌栓(portal vein tumor thrombus,PVTT)是指肝癌细胞侵犯进入门静脉,并在门静脉内增殖形成癌栓.临床上PVTT常见于肿瘤同侧的门静脉分支,可沿门静脉分支向主干方向生长.PVTT的出现意味着肝癌细胞的转移扩散,并因癌栓引起门静脉压力增高而增加消化道出血、腹腔积液、黄疸、肝性脑病和肝衰竭的发生率 [1].PVTT是肝癌预后不良的重要因素,也是影响肝癌整体疗效提高的"瓶颈",合并PVTT中晚期肝癌患者的平均中位生存时间仅为2.7个月.因此肝癌合并PVTT的疗效直接关系到能否改善中晚期肝癌患者的整体生存率.欧美国家的肝癌诊治指南均将PVTT视为肝移植、肝切除、射频消融、TACE的禁忌证 [2-3],对此中西方的专家存在较大争议.

HCC is the sixth most common malignancies worldwide (Parkin et al., 2005) and its incidence is continuous increasing recently (El-Serag et al., 1999). Surgical resection is regarded as a potentially curative treatment for patients with HCC and it has become a safe operation with very low morbidity and mortality rates because of the improvement in surgical techniques and perioperative managements (Fan et al., 1999). However, the long term survival remains unsatisfactory as results of high postoperative recurrence rate which was reported ranged from 65% to 80% in 5-year after primary surgery (Poon et al., 2002; Imamura et al., 2003; Kamiyama et al., 2009), and most of the postoperative recurrences occur in liver remnant (Poon et al., 1999; Taketomi et al., 2010). Intrahepatic recurrence of HCC after surgical resection could originate from either intrahepatic metastasis (IM) from the primary tumor or multicentric occurrence (MO)

Objective To explore the efficacy and safety of preoperative transarterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein invasion. Methods Two hundred and nineteen patients, diagnosed as rescetable HCC and portal vein tumor thrombus (PVTT) via preoperative imaging and multidisciplinary consultation, were prospectively enrolled and allocated into two groups. In the immediate resection group (132 cases), patients received immediate surgical resection. In the preoperative TACE group (87 cases), patients underwent TACE before surgical resection. Stratal analysis was carried out of the survival difference between the two groups. Results The 1-, 3-, 5-year overall survival rates and the median survival time were 52.4%, 19.1%, 13.1%, and 13.87 months for the immediate resection group; 57.1%, 27.2%, 21.1%, and 16.13 months for the preoperative TACE group (P=0.037). On the strata analysis of segmental PVTT group, the overall survival rates of the immediate resection group and preoperative TACE group were 61.0%and 92.9%at 1-year, 32.1%and 55.7%at 3-year, 20.1%and 47.8%at 5-year, respectively (P=0.012). However, comparing the 1-, 3-, 5-year overall survival rates between the two groups respectively, no significant difference was found of major PVTT group (P=0.272). No significant difference was found between the 2 groups in postoperative complications and hospital mortality. Conclusion The preoperative TACE is a safe and effective procedure for patients diagnosed as HCC with portal vein tumor thrombi, and will not increase the incidence of complications, especially for resectable HCC with segmental PVTT.

Objective To evaluate the efficacy of diverse treatment for hepatocellular carcinoma with hypersplenism.Methods The clinical data of 63 patients of hepatocellular carcinoma with hypersplenism from 2007 to 2010 were retro spectively analyzed,26 patients only accepted hepatectomy (group Ⅰ),18 patients accepted hepatectomy in combination with splenectomy or splenic artery ligation (group Ⅱ),and 19 patients underwent partial splenic embolization (PSE) before operation (group Ⅲ).The platelets,white blood cells,complication,intro-operative blood loss and transfusion requirement and survival were analyzed retrospectively.Results The WBC and PLT counts in the blood samples of the PSE group were higher than those in the single operation group after operation.There were no singnificant differences in the WBC and PLT counts between the PSE group and the combined group.Intro-operative blood loss and transfusion requirement in the PSE group were lower than in the single operation group and the combined group (P < 0.05).Postoperative complications in the PSE group and the combined group were significantly less than that in the single operation group.The 1-year and 3-year survival rates were 68.5% and 38.1% for group Ⅰ,82.8% and 52.6% for group Ⅱ,85.5% and 56.3% for group Ⅲ,respectively.Conclusion Synchronous splenectomy and preoperativ PSE can increase the safety and effectiveness of hepato cellular carcinoma with hypersplenism.The treatment of preoperative PSE is more suitable for severe portal hypertension,the megalosplenia,older age and physical poor patients.

Objective To explore the safety and efficacy after two strategies for resectable hepatocellular carcinoma(HCC) with tumor thrombosis(PVTT) in major branch of portal vein.Methods One hundred and sixteen consecutive resesectable HCC with major branch PVTT and excellent liver reserves(Child-pugh A) patients were enrolled and allocated into two groups.Patients of the operation group(56 cases) received initial hepatic resection.In the TACE group(60 cases),patients received transarterial chemoembolization as initial treatment,and only patients who showed good response(CR or PR) were subjected to surgical resection,that was TACE + resection group.Results The morbility and mortality were 28.57%(16/56) and 1.78%(1/56) for the operation group and 11.67%(7/60) and 0(0/60) for the TACE group(P = 0.010).The median time and 1-,2-,5-years were 11.41 months,47.27%,24.58%,5.67% for the operation group.15.34 months,53.91%,17.18%,6.34% for the TACE group.22.01 months,79.17%,45.83%,16.67% for the TACE + resection group.There was no significant survival benefits between the operation and TACE group(P = 0.731),while the TACE + resection group showed significant survival benefits compared the operation group(P = 0.040).Liver cirrhosis and tumor location were independent predicitive factors of a favourable outcome.Conclusion Initial chemoembolization and selective resection may be a safer and effective treatment stragegy,compared with direct sugrery for compensatory liver function patients with resectable HCC and major branch portal vein invasion.