原发胆囊管癌和胆囊底部癌的诊断和治疗

目的:总结分析原发性胆囊管癌与胆囊底体部癌的诊疗不同之处。方法 :将46例胆囊癌分为胆囊底体部和胆囊管部两组,进行回顾性分析,对手术方式、术后情况、中位生存期、淋巴结转移率等指标进行统计。结果:胆囊底体部癌和胆囊管癌的发生发展规律、手术方式等皆有不同,胆囊管癌的淋巴结转移率较高,误诊率高。结论:胆囊管癌在临床表现及处理方法方面有其特殊性,针对胆囊管癌可采取更为积极的手术方式。

原发性胆囊管癌

原发胆囊管癌非常少见。我院收治原发胆囊管乳头状癌兼瘤体脱入总胆管引起黄疸一例。病例摘要刘××,女,62岁,右上腹肿物2年,1978年7月14日入院。二年前右上腹轻微疼痛,并发现一梨形光滑肿物,随呼吸上下移动。近2月右上腹疼痛加重,伴有间歇性发冷发热,恶心呕吐,明显消瘦。两周来全身出现进行性黄染,皮肤搔痒,不思饮食,全身虚弱。

胆囊管癌致胆道出血

1病历简介 孙备医师（哈尔滨医科大学附属第一医院胰胆外科）病人女，69岁。主诉：间断洼上腹痛2个月，加重伴黑便1d。2010—11—21再次出现右上腹胀痛，阵发性加重，伴恶心、黑便、尿色加深，门诊以“梗阻性黄疸”急诊收入消化内科。2个月病程中，食欲下降，排黑便3次，体重下降约2．5kg。

胆囊管癌的临床特点及其手术治疗要点

虽然胆囊管属于胆囊的一部分,但胆囊管癌与胆囊癌存在诸多不同的临床病理学特点,包括肿瘤分型、人口学特征、临床表现、影像学及病理学特点。根治性手术切除(R0切除)是胆囊管癌首选的治疗手段,也是唯一有治愈希望的方法,因此对于无远处转移、全身情况良好的胆囊管癌病人应该积极实施以根治为目的的切除手术。具体手术治疗方式应根据肿瘤侵犯的范围而定。临床上对胆囊管癌的认识尚存在一些争议,有待进一步积累更多更大宗的多中心临床研究结果,以及进一步探索阐明其肿瘤生物学行为特点。

胆囊管癌的临床特点、分型及其手术治疗探讨(附50例报告)

目的探讨胆囊管癌(CDC)的临床特点、分型及其合理的手术方式。方法回顾性分析2007年1月至2021年12月在海军军医大学第三附属医院行手术治疗的50例CDC病人的临床资料。依据有无梗阻性黄疸及肿瘤侵犯胆囊、肝外胆管的范围,提出了CDC的东方肝胆外科医院分型(EHBH分型),并分析其临床特点、手术方式、围手术期结果等。结果50例病人中,男38例(76%),女12例(24%),平均年龄为(63.5±10.1)岁。临床症状黄疸36例(72%)、腹痛33例(66%)、黄疸合并腹痛21例(42%)。EHBH分型:Ⅰa型2例、Ⅰb型1例、Ⅰc型9例、Ⅰd型2例、Ⅱa型26例、Ⅱb型10例。50例病人中,行CDC根治性切除术,即胆囊及肝外胆管切除、区域淋巴结清扫(含No.8、12、13淋巴结)、胆肠吻合、联合或不联合部分肝脏(Ⅳb、Ⅴ段,楔形的胆囊床肝组织或右半肝)切除28例,其中12例(42.9%)联合肝脏切除,16例(57.1%)未联合肝脏切除;余22例行非根治性手术,包括胆囊切除和(或)胆道探查、T管引流或胆管-空肠吻合术等。28例根治性切除病人中15例(53.6%)获得随访,其中2例因全身感染,术后1个月内死亡,余13例中位生存时间为25个月;该13例中8例未行联合肝脏切除,5例行联合肝脏切除,两组间生存时间差异无统计学意义(P>0.05)。结论重视CDC的“腹痛、黄疸、胆囊肿大”三联征,结合影像学及超声内镜检查可提高诊断率。CDC的EHBH分型可以简洁、直观地帮助临床制定手术治疗策略。手术方式推荐以胆囊切除、肝外胆管切除、胆肠吻合及区域淋巴结(No.8、12、13淋巴结)清扫为基本术式,对于累及胆囊颈、体部(特别是腹侧)、尚无明确肝脏浸润的CDC,特别是在高龄、高危病人中,可不联合肝脏切除;而肿瘤累及胆囊颈、体部(肝侧)、存在明确肝脏浸润时,则需要联合局部肝脏切除。

Diagnosis and Treatment of Liver Cystadenocarcinoma:Report of 18 Cases

Objective： To discuss the diagnosis and treatment of liver cystadenocarcinoma. Methods： The clinical, imaging, and pathological data of 18 patients with liver cystadenocarcinoma between January 2000 and December 2004 in our hospital were retrospectively analyzed. Results： The liver cystadeno- carcinoma was seen in males and females （m/f： 9/9）; mean age was 51 years. Ultrasonography revealed cystic parenchymatous mass echoes of fluid predominance with uneven margins. Nonenhanced CT revealed intrahepatic low-density space occupying shadows with nodular protrusions on the margins in all cases. Enhancement CT revealed that part of the nodular protrusions and tissues around the lesions were enhanced and the delayed phase disappeared. 66.67% （12/18） of the lesions were more than 10 cm in diameter. The diagnosis of liver cystadenocarcinoma was confirmed by postoperative pathology in all cases. Of these patients, 12 lesions were in the left lobe, 3 in the right lobe, 1 in the mid lobe, 1 in the right and left lobe, and 1 in the caudate lobe. Of tile 18 patients, 6 had completely resect the cystadenocarcinoma, 2 were surgically explored, one received TAE＋fine needle aspiration cytology＋injection of chemotherapy drugs, and 9 underwent radical hepatectomy＋choledochostomy or T-tube drainage, in which, one patient underwent choledochostomy＋left hepatectomy＋radical gastrectomy for cancer＋lymphadenectomy; one patient underwent resection of the cystadenocarcinoma, who had relapse 20 months after the initial procedure. The patient received repeat reseet for the recurrent cystadenoeareinoma＋eholangio-jejunostomy. Six months later she had another relapse and received repeat reseet （only PMCT） for the recurrent cystadenoearcinoma. The patient died from eholangiopleural fistula after third time operation （PMCT） was attempted perioperatively. Seven patients died of metastatic disease after operation. The remaining 10 patients were alive without cancer recurrence or metastasis （mean follow-up 20 months）. Conclusion： Liver eystadenocarcinoma is rarely seen and grows slowly. It shows some typical clinical and imaging features. The crux for diagnosing and treating liver cystadenoeareinoma is how familiar the surgeon is with the pathology and clinical features of the condition. Prolonged survival can be achieved by radical resection of the tumor.

胆囊癌外科治疗的思考与进展

胆囊癌(gallbladder cancer,GBC)作为胆道系统最常见的恶性肿瘤,我国每年新发病率约5.28万例,其发病率在所有消化系统恶性肿瘤中位列第6位[1]。其起病隐匿,病程进展迅速,严重地威胁着人类健康[2-3]。多数胆囊癌患者就诊时已处于晚期,且常合并肝脏、淋巴结及其他脏器转移,因此其预后极差。

Effect of histone deacetylase inhibitor on proliferation of biliary tract cancer cell lines

AIM: To explore the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the growth of biliary tract cancer cell lines (gallbladder carcinoma cell line and cholangiocarcinoma cell line) in vivo and in vitro, and to investigate the perspective of histone deacetylase inhibitor in its clinical application. METHODS: The survival rates of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) treated with various doses of TSA were detected by methylthiazoy tetrazolium (MTT) assay. A nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-l cell line) was successfully established, and changes in the growth of transplanted tumor after treated with TSA were measured. RESULTS: TSA could inhibit the proliferation of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) in a dose-dependent manner. After the nude mouse model of transplanted gallbladder carcinoma (Mz- ChA-l cell line) was successfully established, the growth of cancer was inhibited in the model after treated with TSA. CONCLUSION: TSA can inhibit the growth of cholangiocarcinoma and gallbladder carcinoma cell lines in vitro and in vivo.

Analysis of p53 and vascular endothelial growth factor expression in human gallbladder carcinoma for the determination of tumor vascularity

AIM： To examine the expression of p53 and vascular endothelial growth factor （VEGF） as well as microvessel count （MVC） and to investigate the role of VEGF as an angiogenic marker and the possible role of p53 in the regulation of angiogenesis in human gallbladder carcinoma. METHODS： Surgically resected specimens of 49 gallbladder carcinomas were studied by immunohistochemical staining for p53 protein, VEGF, and factor VIII-related antigen. VEGF expression and mutant p53 expression were then correlated with Nevin stage, differentiation grade, MVC, and lymph node metastasis. RESULTS： Positive p53 protein and VEGF expressions were found in 61.2% and 63.3% of tumors, respectively. p53 and VEGF staining status was identical in 55.1% of tumors. The Nevin staging of p53- or VEGF-positive tumors was significantly later than that of negative tumors. The MVC in p53- or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-negative tumors was significantly lower than that in the other subgroups. CONCLUSION： Our findings suggest that pS3-VEGF pathway can regulate tumor angiogenesis in human gallbladder carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the tumor vascularity of gallbladder cancer.

Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma

AIM:To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma.METHODS:One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks.Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies.We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining.Coexistent nuclear localization was evaluated.Clinicopatho-logical parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4.RESULTS:Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells,as well as showing weak cytoplasmic expression in non-neoplastic cells.By semiquantitative evaluation,positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%),Notch receptor 2 in 97 (88.2%),Notch receptor 3 in 97 (88.2%),Notch receptor 4 in 103 (93.6),and DLL4 in 84 (76.4%).In addition,coex- istent nuclear localization was noted [Notch receptor 1;18 cases (18.8%),Notch receptor 2;40 (41.2%),Notch receptor 3;32 (33.0%),Notch receptor 4;99 (96.1%),DLL4;48 (57.1%)].Notch receptor 1 expression was correlated with advanced tumor,node,metastasis (TNM) stage (P=0.043),Notch receptor 3 with advanced T stage (P=0.017),tendency to express in cases with nodal metastasis (P=0.065) and advanced TNM stage (P=0.052).DLL4 expression tended to be related to less histological differentiation (P=0.095).Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P=0.027) and Notch receptor 4 with less histological differentiation (P=0.036),while DLL4 tended to be related inversely with T stage (P=0.053).Coexistent nuclear localization of DLL4 was related to poor survival (P=0.002).CONCLUSION:Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression,and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.

Incidental gallbladder cancer during laparoscopic cholecystectomy:Managing an unexpected finding

AIM:To evaluate the impact of incidental gallbladder cancer on surgical experience.METHODS:Between 1998 and 2008 all cases of cholecystectomy at two divisions of general surgery,one university based and one at a public hospital,were retrospectively reviewed.Gallbladder pathology was diagnosed by history,physical examination,and laboratory and imaging studies [ultrasonography and computed tomography(CT)].Patients with gallbladder cancer(GBC) were further analyzed for demographic data,and type of operation,surgical morbidity and mortality,histopathological classification,and survival.Incidental GBC was compared with suspected or preoperatively diagnosed GBC.The primary endpoint was diseasefree survival(DFS).The secondary endpoint was the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention.RESULTS:Nineteen patients(11 women and eight men) were found to have GBC.The male to female ratio was 1:1.4 and the mean age was 68 years(range:45-82 years).Preoperative diagnosis was made in 10 cases,and eight were diagnosed postoperatively.One was suspected intraoperatively and confirmed by frozen sections.The ratio between incidental and nonincidental cases was 9/19.The tumor node metastasis stage was:pTis(1),pT1a(2),pT1b(4),pT2(6),pT3(4),pT4(2);five cases with stageⅠa(T1 a-b);two with stageⅠb(T2 N0);one with stage Ⅱa(T3 N0);six with stage Ⅱb(T1-T3 N1);two with stage Ⅲ(T4 Nx Nx);and one with stage Ⅳ(Tx Nx Mx).Eighty-eight percent of the incidental cases were discovered at an early stage(≤Ⅱ).Preoperative diagnosis of the 19 patients with GBC was:GBC with liver invasion diagnosed by preoperative CT(nine cases),gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum(one case),porcelain gallbladder(one case),gallbladder adenoma(one case),and chronic cholelithiasis(eight cases).Every case,except one,with a T1b or more advanced invasion underwent Ⅳb + Ⅴ wedge liver resection and pericholedochic/hepatoduodenal lymphadenectomy.One patient with stage T1b GBC refused further surgery.Cases with Tis and T1a involvement were treated with cholecystectomy alone.One incidental case was diagnosed by intraoperative frozen section and treated with cholecystectomy alone.Six of the nine patients with incidental diagnosis reached 5-year DFS.One patient reached 38 mo survival despite a port-site recurrence 2 years after original surgery.Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5-year DFS.CONCLUSION:Laparoscopic cholecystectomy does not affect survival if implemented properly.Reoperation should have two objectives:R0 resection and clearance of the lymph nodes.

Is combined extra-hepatic bile-duct resection justified for advanced gallbladder carcinoma?

Background:Whether the extra-hepatic bile duct(EHBD)should be routinely resected for gallbladder carcinoma(GBC)remains controversial.The current study aimed to determine the clinical impact of combined EHBD resection during curative surgery for advanced GBC.Methods:In total,213 patients who underwent curative surgery for T2,T3 or T4 GBC were enrolled.The clinicopathological features were compared between the patients treated with EHBD resection and those without EHBD resection.Meanwhile,univariable and multivariable Cox-proportional hazards regression models were used to identify risk factors for overall survival(OS).Results:Among the 213 patients identified,87(40.8%)underwent combined EHBD resection.Compared with patients without EHBD resection,patients with EHBD resection suffered more post-operative complications(33.3%vs.21.4%,P=0.046).However,the median OS of the EHBD resection group was longer than that of the non-EHBD resection group(25 vs.11 months,P=0.008).Subgroup analyses were also performed according to tumor(T)category and lymph-node metastasis.The median OS was significantly longer in the EHBD resection group than in the non-EHBD resection group for patients with T3 lesion(15 vs.7 months,P=0.002),T4 lesion(11 vs.6 months,P=0.021)or lymph-node metastasis(12 vs.7 months,P<0.001).No survival benefit of EHBD resection was observed in GBC patients with T2 lesion or without lymph-node metastasis.T category,lymph-node metastasis,margin status,pre-operative CA19-9 level and EHBD resection were identified as independent prognostic factors for OS of patients with advanced GBC(all P values<0.05).Conclusions EHBD resection can independently affect the OS in advanced GBC.For GBC patients with T3 lesion,T4 lesion and lymph-node metastasis,combined EHBD resection is justified and may improve OS.