机器人与开腹手术治疗肝内胆管细胞癌患者近期疗效研究*

目的 比较机器人与传统开腹手术行肝叶切除术治疗肝内胆管细胞癌(ICC)患者的安全性和短期疗效。方法 2019年1月～2020年12月我院诊治的ICC患者27例,其中9例接受机器人手术,18例接受传统开腹肿瘤根治术,比较两组手术情况。结果 两组均完成肿瘤根治术;机器人组和开腹组患者手术时间【(198±32)分对(215±74)分】、术中出血量【200(100,250) ml对(275(200,300)ml】和术中输血次数(0次对2次)均无统计学差异(P>0.05);机器人组和开腹组患者肿瘤直径【4.0(2.5,5.5) cm 对6.3(3.9,6.5) cm】、R0切除率(100.0%对88.0%)和淋巴结转移率(44.4%对38.9%)比较,差异无统计学意义(P>0.05);机器人组术后卧床时间和住院日分别为2(1,2.5)d和7(4,8)d,显著短于开腹组【分别为3(1.8,3.5)d和11(8,12)d,P<0.05】,机器人组住院费用为11.3(9.1,13.5)万,与开腹组的10.1(8.8,11.5)万比,无统计学差异(P>0.05);两组术后并发症发生率为11.1%和27.8%,无统计学差异(P>0.05)。结论 开展机器人肿瘤根治术治疗ICC患者安全,术后恢复快。     

Clinical parameters predicting survival duration after hepatectomy for intrahepatic cholangiocarcinoma

BACKGROUND:

Currently, the most effective treatment for intrahepatic cholangiocarcinoma (ICC) is complete hepatic tumour excision.

OBJECTIVE:

To identify the clinical parameters associated with survival duration for ICC patients following hepatectomy, and to construct a mathematical model for predicting survival duration.

METHODS:

Demographic data and clinical variables for 102 patients diagnosed with ICC, who underwent exploratory laparotomy at a single centre from July 1998 to December 2000 and were followed for an average of 24 months, were collected in 2011. Patients were randomly assigned into training (n=76) and validation (n=26) groups. Univariate and multivariate analyses were performed to identify factors associated with posthepatectomy survival duration.

RESULTS:

Univariate analysis revealed that more than three lymph node metastases, a serum carbohydrate antigen 19-9 level >37 U/mL, stage IVa tumours, and intra- or perihepatic metastases were significantly associated with decreased survival duration. Curative resection was significantly associated with increased survival duration. A mathematical model incorporating parameters of age, sex, metastatic lymph node number, curative surgery, carbohydrate antigen 19-9 concentration, alpha-fetoprotein concentration, hepatitis B, TNM stage and tumour differentiation was constructed for predicting survival duration. For a survival duration of less than one year, the model exhibited 93.8% sensitivity, 92.3% total accuracy and a positive predictive value of 93.8%; for a survival duration of one to three years, the corresponding values were 80.0%, 69.2% and 57.1%, repsectively.

CONCLUSIONS:

The mathematical model presented in the current report should prove to be useful in the clinical setting for predicting the extent to which curative resection affects the survival of ICC patients, and for selecting optimal postoperative treatment strategies.     

肝内胆管癌患者术后预后研究

目的 探讨影响肝内胆管癌（ICC）患者术后生存的因素。方法 2011年12月~2015年2月我院诊治的ICC患者94例,对其中35例行姑息性治疗,即肝内扩张胆管置管引流术,对另59例行根治性肿瘤切除术。采用单因素分析和多因素回归分析影响ICC患者术后生存的因素。结果 经随访,本组94例ICC患者生存期为3~35个月,平均为（26.1±4.6）个月;1 a生存率为76.6%,2a生存率为7.4%;单因素分析显示,ICC肿瘤数目、直径、肿瘤分化、血清CEA、CA19-9和是否发生淋巴结转移和远处转移以及手术方法为影响术后患者生存的因素（P<0.05）;经多因素回归分析,发现肿瘤多发、低程度分化、血清CEA大于25 μg/L、血清CA19-9大于182 U/ml、手术切除组织边缘肿瘤细胞阳性、淋巴结转移和姑息性手术是影响ICC患者术后生存的危险因素（P<0.05）。结论 ICC患者预后差,很多患者在诊断时已失去根治性切除肿瘤的机会,即使获得肿瘤切除而根治的患者仍存在很多影响预后的危险因素,临床医生需认真研究这些因素,而给予相应的处理。     

Liver transplantation for intrahepatic cholangiocarcinoma

The indication of liver transplantation for intrahepatic cholangiocarcinoma (ICC) is highly controversial. Initially, liver transplantation was embraced as a promising treatment for ICC, providing both a wider surgical margin and a potential cure for the underlying liver disease. However, the majority of transplant centers have abandoned liver transplantation for ICC due to poor long‐term survival and high recurrence rates. Interestingly, these decisions were based on studies with highly inconsistent outcomes due to a limited number of patients, various patient selection criteria, and the use of nonstandardized adjunctive therapy protocols. Indeed, recent studies have revealed that ICC patients with small solitary tumors have excellent long‐term survival after liver transplantation. Moreover, as seen in early‐stage hilar cholangiocarcinoma, neoadjuvant and adjuvant therapy hold promise for improved long‐term survival in patients with locally advanced ICC. As we work to expand treatment options for ICC, further evidence of success in this area is needed in order to justify the use of limited organ resources to treat ICC. Continued efforts to improve diagnosis of ICC, hone patient selection criteria, and implement standardized treatment protocols could provide certain patients with ICC access to potentially life‐saving liver transplantation.     

Prognostic value of DNA alterations on chromosome 17p13.2 for intrahepatic cholangiocarcinoma

AIM:To characterize and evaluate DNA alterations among intrahepatic cholangiocarcinoma (ICC) patients. METHODS:DNA from tumor and corresponding normal tissues of 52 patients was amplified with 33 arbitrary primers. The DNA fragment that alters most frequently in ICC was cloned,sequenced,and identified by comparison with known nucleotide sequences in the genome database (www.ncbi.nlm.nih.gov). The DNA copy numbers of the allelic alterations in cholangiocarcinoma were determined by quantitative real-time PCR and interpreted as allelic loss or DNA amplification by comparison with the reference gene. Associations between allelic imbalance and clinicopathological parameters of ICC patients were evaluated by χ2-test. The Kaplan-Meier method was used to analyze survival rates. RESULTS:From 33 primers,an altered DNA fragment (518 bp) amplified from BC17 random primer was found frequently in the tumors analyzed and mapped to chromosome 17p13.2. Sixteen of 52 (31%) cases showed DNA amplification,while 7 (13%) showed allelic loss. Interestingly,DNA amplification on chromosome 17p13.2 was associated with a good prognosis,median survival time (wk) of amp vs no amp was 44.14 vs 24.14,P=0.002; whereas allelic loss of this DNA sequence corresponded with a poor prognosis,median survival time (wk) of loss vs no loss was 18.00 vs 28.71,P=0.019). Moreover,Kaplan-Meier curves comparing the DNA alterations with survival depicted highly significant separation that the median survival time equal to DNAamplification,allelic loss,and normal was 44.14 wk,18.00 wk,and 24.29 wk,respectively (P=0.005). CONCLUSION:Alterations in the DNA sequence on chromosome 17p13.2 may be involved in cholangio-carcinogenesis,and could be used as a prognostic marker in the treatment of ICC patients.     

A case of intrahepatic clear cell cholangiocarcinoma

Intrahepatic clear cell cholangiocarcinoma is very rareonly 8 cases have been reported.A 56-year-old Japanese man with chronic hepatitis B infection was diagnosed with a 2.2 cm hepatocellular carcinoma on imaging,and hepatic segmentectomy was performed.Histopathologically,the tumor cells had copious clear cytoplasm and formed glandular structures or solid nests.These pathological findings suggested the tumor was a clear cell variant of intrahepatic cholangiocarcinoma.Particular stains and radiological image...     

Hepatitis B virus infection: a favorable prognostic factor for intrahepatic cholangiocarcinoma after resection

AIM: To study the prognostic factors for intrahepatic cholangiocarcinoma (ICC) and evaluate the impact of chronic hepatitis B virus (HBV) infection on survival rate of ICC patients. METHODS: A total of 155 ICC patients who underwent macroscopic curative resections (R0 and R1) were enrolled in this retrospective study and divided into group A with HBV infection and group B without HBV infection according to their chronic HBV infection, represented by positive hepatitis B surface antigen (HBsAg) in serum or i...     

Risk factors for intrahepatic cholangiocarcinoma： A casecontrol study in China

AIM： To carry out a hospital-based case-control study to investigate risk factors for intrahepatic cholangiocarcinoma （ICC） in China. METHODS： A total of 312 ICC cases and 438 matched controls were included in the study. The presence of diabetes mellitus, hypertention, hepatolithiasis, primary sclerosing cholangitis, liver fluke infection （Clonorchis sinensis）, was investigated through clinical records. Blood from all participants was tested for hepatitis B surface antigen （HBsAg） and anti-HCV antibodies. Odds ratios （OR） and 95% confidence intervals （95% CI） were estimated using conditional logistic regression. RESULTS： Compared with controls, ICC patients had a higher prevalence of HBsAg seropositivity （48.4% vs 9.6%, P 〈 0.000）, and hepatolithiasis （5.4% vs 1.1%, P = 0.001）. By multivariate analysis, the significant risk factors for development of ICC were HBsAg seropositivity （adjusted OR, 8.876, 95% CI, 5.973-13.192）, and hepatolithiasis （adjusted OR, 5.765, 95% CI, 1.972-16.851）. The prevalence of anti-HCV seropositivity, diabetes mellitus, hypertention, cigarette smoking, and alcohol consumption were not significantly different between cases and controls. CONCLUSION： These findings suggest that HBV infection and hepatolithiasis are strong risk factors for development of ICC in China.     

腹腔镜肝切除术与开腹肝切除术治疗肝内胆管细胞癌患者短期临床疗效研究

目的 研究腹腔镜肝切除术(LH)与开腹肝切除术(OH)治疗肝内胆管细胞癌(ICC)患者的短期临床疗效。方法 2018年2月～2021年2月我院诊治的122例ICC患者,被随机分为对照组61例和观察组61例,分别接受OH或LH治疗,随访观察半年。采用ELISA法检测血清C反应蛋白(CRP)、皮质醇(Cor)和白细胞介素-6(IL-6)。结果 LH组手术时长、术中失血量、肛门首次排气和术后住院日分别为(232.2±50.4)min、(592.3±164.7)ml、(2.1±0.8)d和(6.5±1.3)d,显著短于或少于0H组【分别为(321.1±69.7)min、(995.5±321.4)ml、(2.7±0.7)d和(8.2±1.7)d,P<0.0 5】;在术后3 d时,LH组血清CRP、Cor和IL-6水平分别为(25.1±4.0)mg/L、(529.6±75.4)mmol/L和(83.5±7.2)pg/ml,均显著低于0H组【分别为(39.8±5.1)mg/L、(654.7±78.1)mmol/L和(97.3±10.2)pg/ml,P<0.05】;在术后7 d时,LH组血...     

Current status of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma （ICC） is a rare primary liver cancer with a global increasing trend in recent years. Symptoms tend to be vague and insidious in development, often are diagnosed at an advanced stage when only palliative approaches can be used with a median survival rate of months. Comparing with HCC, ICC tends to spread to lymph nodes early, and is rarely limited to the regional lymph nodes, with a frequent postoperative recurrence. Surgery is the only choice of curative therapy for ICC, but recently no consensus has been established for operation. Thus, more data from multiple centers and more cases are needed. Generally speaking, current adjunctive therapy cannot clearly improve survival. Further research is needed to find more effective radio- and chemotherapeutic regimens.     

Addition of hepatectomy decreases liver recurrence and leads to long survival in hilar cholangiocarcinoma

AIM： To evaluate hepatic recurrence and prognostic factors for survival in patients with surgically resected hilar cholangiocarcinoma in a single institution over the last 13 years. METHODS： From 1994 to 2007, all patients with hilar cholangiocarcinoma referred to a surgical clinic were evaluated. Demographic data, tumor characteristics, and outcome were analyzed retrospectively. Outcome was compared in patients who underwent additional liver resection with resection of the tumor. RESULTS： Of the 69 patients submitted to laparotomy for tumor resection, curative resection （Ro resection） was performed in 40 patients, and palliative resection in 29. Thirty-one patients had only duct resection, and 38 patients had combined duct resection with liver resection including 34 total or part caudate lobes. Curative rates with the combined hepatectomy were significantly improved compared with those without additional hepatectomy （27/38 vs 13/31; X^2 = 5.94, P 〈 0.05）. Concomitant liver resection was associated with a decreased incidence of initial recurrence in liver one year after surgery （11/38 vs 23/31; X^2 = 13.98, P 〈 0.01）. The 3-year survival rate after Ro resection was 30.7% and was 10.5% for palliative resection. R0 resection improved the 3-year survival rate （30.7% vs 10.5%; X^2 = 12.47, P 〈 0.01）.CONCLUSION： Hepatectomy, especially including the caudate lobe combined with bile duct resection should be considered standard treatment to cure hilar cholangiocarcinoma.     

Analysis of intrahepatic sarcomatoid cholangiocarcinoma:Experience from 11 cases within 17 years

BACKGROUND Intrahepatic sarcomatoid chonalgiocarcinoma(s-CCC) is an extremely rare disease, accounting for less than 1% of hepatobiliary system malignancies, and its pathophysiology is not well known. On the hypothesis that its clinical, serologic,or radiologic diagnosis are not fully understood and its prognosis is poor, we investigated the distinguishing features of s-CCC compared with those of intrahepatic bile duct adenocarcinoma [cholangiocellular carcinoma(CCC)] in patients from a single center.AIM To analyze the clinical, serologic, imaging, and histopathologic characteristics of intrahepatic s-CCC patients diagnosed in a single center.METHODS The clinical, serologic, imaging, and histopathologic features of 227 patients diagnosed with intrahepatic cholangiocarcinoma(IHCC) in a single medical center during the last 17 years were analyzed. The characteristics of 11 patients with s-CCC were compared with those of 216 patients with CCC.RESULTS The number of patients with s-CCC who presented fever and abdominal pain and past history of chronic viral hepatitis or liver cirrhosis(LC) was higher than that of patients with CCC. In imaging studies, patients with s-CCC showed relatively aggressive features. However, no clear distinction was observed between s-CCC and CCC based on other clinical, serologic or radiologic examination results. An accurate diagnosis could be made only via a histopathologic examination through immunohistochemical staining. The clinical course of s-CCC was generally aggressive, and patients had a relatively poor prognosis.CONCLUSION In patients with s-CCC, early diagnosis through biopsy and aggressive treatment,including surgical resection, are important.     

Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma

AIM:To investigate the correlation between nerve growth factor-tropomyosin-receptor-kinase(NGF-TrkA)signaling pathway and prognosis in intrahepatic cholangiocarcinoma(IHCC).METHODS:NGF and TrkA expression in 83 samples of IHCC was assessed by immunohistochemistry.Correlations between NGF-TrkA expression and clinicopathological features were analyzed byχ2 test.Moreover,we evaluated the association between NGF-TrkA and overall survival by univariate and multivariate analysis.With experiments in vitro,we investigated the crucial role of NGF-TrkA on proliferation and invasion of IHCC cells with recombinant NGF-βstimulation.RESULTS:We found that NGF and TrkA expression was significantly related with differentiation(P=0.024)and intraneural invasion(P=0.003),respectively.Additionally,double higher expression of NGF and TrkA was identified as an independent prognostic factor in IHCC(P=0.003).Moreover,we demonstrated that NGF-TrkA signaling pathway can promote IHCC proliferation and invasion.CONCLUSION:NGF-TrkA double higher expression is an independent prognostic factor in IHCC.NGF-TrkA pathway can promote IHCC progression,indicating that NGF-TrkA may become a potential drug target.     

Hepatitis B virus and hepatitis C virus play different prognostic roles in intrahepatic cholangiocarcinoma: A meta-analysis

AIM: To identify the prognostic value of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections in patients with intrahepatic cholangiocarcinoma.METHODS: A search was performed for relevant publications in Pub Med, EMBASE and Web of Science databases. The pooled effects were calculated from the available information to identify the relationship between HBV or HCV infection and the prognosis and clinicopathological features. The χ2 and I2 tests were used to evaluate heterogeneity between studies. Pooled hazard ratios(HRs) with 95% confidence intervals(CIs) were calculated by a fixed-effects model, if no heterogeneity existed. If there was heterogeneity, a random-effects model was applied.RESULTS: In total, 14 studies involving 2842 cases were enrolled in this meta-analysis. The patients with HBV infection presented better overall and diseasefree survival, and the pooled HRs were significant at 0.76(95%CI: 0.70-0.83) and 0.78(95%CI: 0.66-0.94), respectively. Additionally, our study revealed that HCV infection was correlated with shortened overall survival in comparison with the control group(HR = 2.64, 95%CI: 1.77-3.93). We also found that HBV infection occurred more frequently in male patients [odds ratio(OR) = 1.91, 95%CI: 1.06-3.44] and was correlated with higher levels of serum aspartate transaminase(AST) and alpha-fetoprotein(AFP)(OR = 1.93, 95%CI: 1.11-3.35; OR = 3.86, 95%CI: 2.58-5.78) and a lower level of serum carbohydrate antigen 19-9(CA19-9)(OR = 0.47, 95%CI: 0.34-0.65). Moreover, HBV infection was associated with cirrhosis(OR = 6.44, 95%CI: 4.33-9.56), a higher proportion of capsule formation(OR = 6.04, 95%CI: 3.56-10.26), and a lower rate of lymph node metastasis(OR = 0.39, 95%CI: 0.25-0.58). No significant publication bias was seen in any of the enrolled studies.CONCLUSION: HBV infection may indicate a favorable prognosis in patients with intrahepatic cholangiocarcinoma, while HCV infection suggests a poor prognosis.