基质金属蛋白酶-2及其抑制物在慢性肝炎和肝硬化肝组织中的表达

为进一步探讨基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-2组织抑制因子（TIMP-2）在肝纤维化发生，发展过程中的作用，用免疫组织化学方法检测慢性肝炎和肝硬化肝组织中MMP-2和TIMP-2的表达及分布状态，并作定位及半定量分析。     

食管鳞癌中基质金属蛋白酶-7的表达及意义

目的:研究基质金属蛋白酶-7(MMP-7)在食管鳞癌中的表达情况及其与肿瘤浸润和淋巴结转移的关系。方法:用免疫组织化学法检测75例食管鳞癌组织及其相应正常粘膜中MMP-7的表达。结果:食管鳞癌组织MMP-7基因表达(59/75,78.7％)高于正常组织(P<0.01)。浸润到外膜层食管鳞癌(37/45,82.2％)与浸润至粘膜下层鳞癌(5/10,50.0％)之间MMP-7的高表达有显著性差异(P<0.05),淋巴结转移组MMP-7高表达(27/29,93.1％)高于淋巴结未转移组(P<0.05)。结论:MMP-7的高表达与食管鳞癌浸润深度和淋巴结转移有关,可能成为食管鳞癌恶性生物学行为的指标。     

组织蛋白酶B、基质金属蛋白酶-2在非小细胞肺癌中的表达及临床意义

目的探讨组织蛋白酶B(CB)和基质金属蛋白酶(MMP)-2在非小细胞肺癌发生、发展及转移中的作用。方法应用免疫组织化学法检测75例非小细胞肺癌组织及28例良性肺病变中CB和MMP-2的表达情况,并将检测结果与临床病理特征进行综合分析。结果 CB和MMP-2的表达主要定位于细胞质,CB和MMP-2在非小细胞肺癌中表达的阳性率明显高于良性肺病变(P0.05)。非小细胞肺癌中MMP-2蛋白的表达与有无淋巴结转移情况密切相关。肺癌组织中CB、MMP-2的表达水平呈显著正相关。结论 CB和MMP-2在非小细胞肺癌中表达上调,联合检测CB和MMP-2对肿瘤的诊断和预后判断有一定的临床意义。     

基质金属蛋白酶在食管癌组织中的表达及与微量元素含量之间的关系

目的:探讨MMP-9、MMP-2及微量元素在食管癌的发生、发展、浸润、转移过程中的作用及相互关系.方法:应用免疫组织化学(immunohistochemistry,IHC)SP法检测49例食管癌及16例癌旁组织中MMP-2、MMP-9蛋白的表达情况与食管癌的病理分型、分化程度、淋巴结转移及患者性别、年龄之间的相互关系.用AA-670原子吸收分光光度计测定食管癌组织中微量元素的含量.并对两者的结果做相关分析.结果:MMP-2、MMP-9蛋白的表达在食管癌中表达明显高于癌旁正常组织(69.3% vs 12.5%,71.4% vs 6.25%),且在有淋巴结转移组明显高于无淋巴结转移组(85.7% vs 47.6%,82.1% vs 52.3%),但在不同病理分型、年龄、性别、分期、分化程度中无明显统计学差异.食管癌组织中Zn含量及Zn/Cu显著低于癌旁正常食管组织Zn含量及Zn/Cu(8.13 μg/g±3.08 μg/g vs 11.63 μg±3.49 μg/g;7.50±3.65 vs 15.40±6.84),同时腺癌的Zn/Cu低于鳞癌的Zn/Cu(4.48±3.52 vs 8.02±3.45),食管腺癌组织中Se的含量显著高于食管鳞癌中Se的含量(0.91 μg/g±1.72 μg/g vs 0.29 μg±0.28 μg/g);有淋巴结转移组癌组织中Zn含量及Zn/Cu显著低于无淋巴结转移组癌组织中Zn含量及Zn/Cu(7.72 μg/g±3.03 μg/g vs 9.59 μg/g±3.06 μg/g;6.91±3.86 vs 9.93±4.81).而不同分化程度、不同分期、不同年龄、不同性别的食管癌中微量元素含量没有明显差别.结论:MMP-2、MMP-9及微量元素Zn的含量及Zn/Cu与在食管癌的发生发展及侵袭转移中可能起重要作用.联合检测微量元素、MMP-2与MMP-9有可能成为判断食管癌生物学行为的客观指标,对判断预后可能有一定价值.     

基质金属蛋白酶9在大肠癌中表达的研究

目的 探讨基质金属蛋白酶9（MMP-9）在大肠癌中的表达及临床意义。方法 采用免疫组织化学SP法检测216例大肠癌组织中MMP-9的表达。结果 216例大肠癌组织MMP-9阳性表达率为76．9％（166／216），高表达率为65．3％（141／216）。MMP-9高表达与大肠癌的分化程度、Dukes分期、生存期、淋巴结转移和器官转移密切相关（P〈0．05或0．01）。结论 MMP-9高表达在大肠癌的侵袭和转移中发挥重要作用。     

Fascin和MMP-9在肝门胆管癌组织中的表达及临床意义

目的:研究Fascin蛋白和基质金属蛋白酶9(matrix metallo proteinase-9,MMP-9)在肝门胆管癌组织中的表达及其与肝门胆管癌的临床生物学行为的关系.方法:应用SP法检测56例肝门胆管癌及14例正常胆管上皮组织中Fascin和MMP-9的表达.结果:Fascin和MMP-9在肝门胆管癌中的表达阳性率都明显高于正常胆管上皮组织(58.9%vs0%,P<0.05)和(73.2%vs14.3%,P<0.05);且Fascin和MMP-9在肝门胆管癌中的表达与肿瘤的组织分化程度、淋巴结转移、门静脉浸润有关(P<0.05);Fascin和MMP-9在肝门胆管癌组织中的表达呈正相关(P<0.05).结论:Fascin和MMP-9在肝门胆管癌的进展、转移中起重要作用,两者之间起相互协同促进作用.     

基质金属蛋白酶-7和基质金属蛋白酶-28在特发性肺纤维化诊断中的价值

目的 探讨基质金属蛋白酶-7(MMP-7)、基质金属蛋白酶-28(MMP-28)在特发性肺纤维化(IPF)诊断及严重程度评估中的临床价值.方法 选2018年9月至2019年12月在宁夏回族自治区人民医院就诊的30例IPF患者为实验组,30例类风湿性关节炎相关间质性肺病(RA-ILD)及30例健康体检者为对照组.测定所有...     

穿膜蛋白1和基质金属蛋白酶9在胆管癌中的表达及意义

目的通过观察胆管癌组织中穿膜蛋白1(DLK1)与基质金属蛋白酶9(MMP-9)的表达,分析两者的临床意义及相关性。方法收集2001-2010年96例胆管癌患者癌组织,20例正常人胆管组织作为对照,采用SP免疫组织化学法检测组织中DLK1与MMP-9的表达。组间比较采用卡方检验,相关性检验采用Spearman相关分析。结果 DLK1与MMP-9在胆管癌中的阳性表达率分别为59.38%和79.17%,2者显著高于在正常胆管组织中的表达(0和15%),差异有统计学意义(χ2=23.35、31.37,P0.05)。胆管癌中DLK1的表达与肿瘤的分化程度相关(χ2=7.46,P0.05);MMP-9的表达与肿瘤的分化程度、淋巴结转移相关(χ2=7.28、9.67,P0.05),与性别、年龄、肿瘤组织大小无关(P0.05)。两者在胆管癌组织中的表达呈正相关(r=0.41,P0.05)。结论 DLK1与MMP-9在胆管癌中高表达,且两者呈正相关,提示可能与胆管癌的发生、发展、侵润、转移有关,其表达的检测为胆管癌的诊断及治疗提供一定的参考依据。     

基质金属蛋白酶组织抑制剂-1在胃癌中的表达及临床意义

在肿瘤转移过程中 ,基底膜基质的降解或多或少地与各种类型的基质金属蛋白酶 ( MMPs)和相应的基质金属蛋白酶组织抑制剂 ( TIMPs)的活性相关。一般来说 ,MMPs降解细胞外基质而促进肿瘤的侵袭转移 ,而 TIMPs通过抑制 MMPs活性对细胞外基质的降解过程起负性调控作用 [1] ,从而抑制肿瘤细胞的侵袭转移。将基质金属蛋白酶组织抑制剂 - 1( TIMP- 1 )基因导入小鼠肿瘤细胞可遏制肿瘤的进展[2 ] 。但亦有些研究显示 ,TIMP- 1与 MMPs之间存在复杂关系 ,TIMP- 1并不抑制肿瘤的进展 ,它作为一种生长因子 ,可促进正常粘膜细胞抑或恶性细胞…     

基质金属蛋白酶-2和-9在食管鳞状细胞癌中的过表达

目的 探讨人食管鳞癌组织中基质金属蛋白酶(MMP)-2、-9的表达及其临床意义.方法 采用免疫组织化学法,检测57例食管鳞癌及10例食管正常黏膜石蜡标本中MMP-2、-9蛋白的表达情况.结果 食管鳞癌组织中MMP-2及MMP-9阳性表达率(40.3%,61.4%)显著高于正常组织(0.0%,10.0%)(P＜0.05).食管鳞癌组织中MMP-2及MMP-9阳性表达与淋巴结转移和癌组织浸润深度有显著相关性(P＜0.05),而与患者的性别、年龄和组织分化程度无显著相关性(P＞0.05).结论 MMP-2和MMP-9在食管癌中显著高表达,与食管癌的转移及侵袭有关,其异常表达可能共同参与食管癌的发生、发展过程,检测MMP-2、-9可作为食管癌病理学特点的参考指标.     

Thermo-chemo-radiotherapy for advanced bile duct carcinoma

AIM: Complete resection of the bile duct carcinoma is sometimes difficult by subepithelial spread in the duct wall or direct invasion of adjacent blood vessels. Nonresected extrahepatic bile duct carcinoma has a dismal prognosis, with a life expectancy of about 6 mo to 1 year. To improve the treatment results of locally advanced bile duct carcinoma, we have been conducting a clinical trial using regional hyperthermia in combination with chemoradiation therapy. METHODS: Eight patients complaining of obstructive jaundice with advanced extrahepatic bile duct underwent thermo-chemo-radiotherapy (TCRT). All tumors were located in the upper bile duct and involved hepatic bifurcation, and obstructed the bile duct completely. Radiofrequency capacitive hyperthermia was administered simultaneously with chemotherapeutic agents once weekly immediately following radiotherapy at 2 Gy. We administered heat to the patient for 40 min after the tumor temperature had risen to 42 ℃. The chemotherapeutic agents employed were cis-platinum (CDDP, 50 mg/m2) in combination with 5-fluorouracil (5-FU, 800 mg/m2) or methotrexate (MTX, 30 mg/m2) in combination with 5-FU (800 mg/m2). Number of heat treatments ranged from 2 to 8 sessions. The bile duct at autopsy was histologically examined in three patients treated with TCRT. RESULTS: In respect to resolution of the bile duct, there were three complete regression (CR), two partial regression (PR), and three no change (NC). Mean survival was 13.2±10.8 mo (mean±SD). Four patients survived for more than 20 mo. Percutaneous transhepatic biliary drainage (PTBD) tube could be removed in placement of self-expandable metallic stent into the patency-restored bile duct after TCRT. No major side effects occurred. At autopsy, marked hyalinization or fibrosis with necrosis replaced extensively bile duct tumor and wall, in which suppressed cohesiveness of carcinoma cells and degenerative cells were sparsely observed. CONCLUSION: Although the number of cases is rather small, TCRT in the treatment of locally advanced bile duct carcinoma is promising in raising local control and thus, long-term survival.     

Surgical treatment of hepatocellular carcinoma with bile duct tumor thrombi

AIM: To study the surgical treatment effect and outcome of hepatocellular carcinoma (HCC) with bile duct tumor thrombi (BDTT). METHODS: Fifty-three consecutive HCC patients with BDTT admitted in our department from July 1984 to December 2002 were reviewed retrospectively. The clinical data, diagnostic methods, surgical procedures and outcome of these patients were collected and analyzed. RESULTS: One patient rejected surgical treatment, 6 cases underwent percutaneous transhepatic cholangial drainage (PTCD) for unresectable primary disease, and the other 46 cases underwent surgical operation. The postoperative mortality was 17.6%, and the morbidity was 32.6%. Serum total bilirubin levels of these patients with obstructive jaundice decreased gradually after surgery. The survival time of six cases who underwent PTCD ranged from 2 to 7 mo (median survival of 3.7 mo). The survival time of the patients who received surgery was as follows: 2 mo for one patient who underwent laparotomy, 5-46 mo (median survival of 23.5 mo, which was the longest survival in comparison with patients who underwent other procedures, P=0.0024) for 17 cases who underwent hepatectomy, 5-17 mo (median survival of 10.0 mo) for 5 cases who underwent HACE, 3-9 mo (median survival of 6.1 mo) for 11 cases who underwent simple thrombectomy and biliary drainage, and 3-8 mo (median survival of 4.3 mo) for four cases who underwent simple biliary drainage. CONCLUSION: Jaundice caused by BDTT in HCC patients is not a contraindication for surgery. Only curative resection can result in long-term survival. Early diagnosis and surgical treatment are the key points to prolong the survival of patients.     

A case of peribiliary cysts accompanying bile duct carcinoma

A rare case of peribiliary cysts accompaying bile duct carcinoma is presented. A 54-year-old man was diagnosed as having lower bile duct carcinoma and peribiliary cysts by diagnostic imaging. He underwent pylorus preserving pancreatoduodenectomy. As for the peribiliary cysts, a course of observation was taken. Over surgery due to misdiagnosis of patients with biliary malignancy accompanied by peribiliary cysts should be avoided.     

An autopsy case of granulocyte-colony-stimulating-factor-producing extrahepatic bile duct carcinoma

A 79-year-old man was referred to this department due to the presence of extrahepatic bile duct carcinoma with a tumor at the left chest wall. The lesion was suspected to be a metastasis of bile duct carcinoma to the left wall, however, computed tomography （CT） revealed no regional lymph node or liver metastases. In addition, cytological and pathological examinations did not show malignancy. At the time of admission, the white blood cell count was 21 460 cells/μL （neutrophils, 18 240 cells/μL） and this elevated to 106 040 before death. In addition, serum granulocyte colony-stimulating factor （G-CSF） was elevated. At 28 d after admission, the patient died. An autopsy showed a poorly differentiated adenocarcinoma with sarcomatous change, which had slightly invaded into the pancreas around the bile duct, and was found in the distal bile duct with multiple metastases to the chest wall, lung, kidney, adrenal body, liver, mesentery, vertebra and mediastinal and para-aortic lymph nodes, without locoregional lymph node and liver metastasis. The cancer cells showed positive immunohistochemical staining for anti-G-CSF antibody. This is believed to be the first report of an extrahepatic bile duct carcinoma that produces G-CSF. Since G-CSF-producing carcinoma and sarcomatous change of the biliary tract leads to poor prognosis, early diagnosis and treatment are needed. When infection is ruled out, the G-CSF in serum should be examined. In addition, examinations such as bonescintigraphy and chest CT should also be considered for distant metastasis.     

Mucosal bile duct carcinoma with superficial spread

We describe a case of mucosal bile duct carcinoma with superficial spread in a 69-year-old man with gallstone pancreatitis. The patient was seen at the hospital because of abdominal pain, fever, and jaundice. Endoscopic retrograde cholangiography (ERC) demonstrated a protruding lesion in the lower third of the common bile duct (CBD) showing wall irregularity suggestive of malignancy. Percutaneous transhepatic cholangioscopy (PTCS) disclosed a papillary tumor with granular mucosa extending continuously to the middle third of the CBD. Cholangioscopic biopsy specimens taken from both the papillary tumor and surrounding granular mucosa revealed papillary adenocarcinoma. After this assessment of extent of cancer by PTCS, we performed pancreatoduodenectomy with extrahepatic bile duct resection and regional lymph node dissection. Pathology examination revealed papillary adenocarcinoma limited to the mucosal layer. The resected margin of the bile duct was free of tumor. We also reviewed 25 cases of early mucosal bile duct carcinoma described in detail in the Japanese literature, and we discuss the diagnostic advantages of PTCS.     

胆道肿瘤组织中ubiquitin的表达及临床意义

目的研究人胆道系统肿瘤中泛素（ubiquitin）蛋白的表达与胆道系统肿瘤不同病理分型的关系及其临床意义。方法采用免疫组织化学法结合蛋白印迹技术检测人胆道肿瘤组织、正常胆道组织及炎性组织中泛素蛋白的表达,分析人胆道肿瘤组织中泛素蛋白的表达情况与不同临床病理情况之间的相关性。结果人胆道肿瘤组织中泛素蛋白的表达显著高于正常组织及炎性组织中泛素蛋白的表达（P〈0．05）。泛素蛋白的表达与病理组织学分级有明显相关性（P〈0．05）。结论泛素蛋白在人胆道肿瘤组织中表达水平升高,可能与胆道系统肿瘤的恶性程度、疾病的进程有密切的关系。     

Diagnosis of bile duct hepatocellular carcinoma thrombus without obvious intrahepatic mass

AIM:To study the diagnosis of hepatocellular carcinoma(HCC)presenting as bile duct tumor thrombus with no detectable intrahepatic mass.METHODS:Six patients with pathologically proven bile duct HCC thrombi but no intrahepatic mass demonstrated on the preoperative imaging or palpated intrahepatic mass during operative exploration,were collected.Their clinical and imaging data were retrospectively analyzed.The major findings or signs on comprehensive imaging were correlated with the surgical and pathologic findings.RESULTS:Jaundice was the major clinical symptom of the patients.The elevated serum total bilirubin,direct bilirubin and alanine aminotransferase levels were in concordance with obstructive jaundice and the underlying liver disease.Of the 6 patients showing evidence of viral hepatitis,5 were positive for serum alpha fetoprotein and carbohydrate antigen 19-9,and 1 was positive for serum carcinoembryonic antigen.No patient was correctly diagnosed by ultrasound.The main features of patients on comprehensive imaging were filling defects with cup-shaped ends of the bile duct,with large filling defects presenting as casting moulds in the expanded bile duct,hypervascular intraluminal nodules,debris or blood clots in the bile duct.No obvious circular thickening of the bile duct walls was observed.CONCLUSION:Even with no detectable intrahepatic tumor,bile duct HCC thrombus should be considered in patients predisposed to HCC,and some imaging signs are indicative of its diagnosis.     

A case of benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma

We report a patient with benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma. A 66-year-old woman consulted a local physician because of general fatigue. Blood biochemical tests showed increased levels of biliary tract enzymes. Abdominal ultrasonography (US) revealed tapering and blockage of the midportion of the bile duct and dilation of the intrahepatic bile ducts. Magnetic resonance cholangiopancreatography (MRCP) demonstrated obstruction of the midportion of the bile duct. Later, because a marked increase in biliary tract enzymes and jaundice appeared, percutaneous transhepatic biliary drainage (PTBD) was performed. Post-PTBD cytological examination of bile was negative for cancer. A third biopsy showed slight hyperplasia with no malignant findings. Recholangiography, performed through PTBD, suggested gradual improvement of bile duct stricture, but could not completely exclude the possibility of malignancy; thus, resection of the bile duct including the stricture site was performed, and the resected specimen was submitted for intraoperative frozen section examination. Histopathological diagnosis did not reveal malignant findings. After cholecystectomy and bile duct resection, hepaticojejunostomy (Roux-en-Y) was performed. Because only erosion and desquamation of the mucosal epithelium and mild submucosal inflammatory cell infiltration and fibrosis were observed, chronic cholangitis was diagnosed histopathologically. Surgical resection of the bile duct should be considered for potentially malignant stricture of the bile duct.     

Hilar bile duct resection for bile duct carcinoma at the hilus of the liver

Hilar bile duct resection, by which only the bile duct is resected, was carried out in 31 patients with bile duct carcinoma at the hepatic hilus. However, curative resection was possible in only 4 patients (12.9%). The postoperative 1-, 3-, and 5-year survival rates were 58.1%, 19.4%, and 7.7%, respectively. These results indicate that treatment of this hilar bile duct carcinoma by hilar bile duct resection is of limited value. We believe that this operative procedure should be used only for papillary or nodular carcinoma at the hepatic confluence at relatively early stages of Bismuth's type I or II.     

Frozen section and permanent diagnoses of the bile duct margin in gallbladder and bile duct cancer

Hypothesis. Frozen section diagnosis and permanent diagnosis of bile duct margin predict local recurrence after surgical resection of gallbladder or bile duct carcinoma. Design. Retrospective review. Setting. University, tertiary care. Patients. A total of 20 patients underwent frozen section diagnosis of bile duct margin for resection of gallbladder and bile duct carcinoma. Main outcome. Diagnosis of frozen and permanent section of bile duct margin, and local recurrence. Results. The permanent diagnosis was identical in 15 patients but changed in 5 (from positive to negative in 3 and from negative to positive in 2). The reasons for these changes were overdiagnosis (mucosal lesions in two and mesenchymal components in another) and new recognition of malignant cells on permanent section in the other two. In seven patients with a positive bile duct margin by permanent histology, mucosal spread was evident in two and involvement of the subepithelial layer was present in the other five. No local recurrence occurred in the two patients with epithelial spread and four of the five with subepithelial infiltration. Conclusions. Frozen section and permanent diagnoses of the bile duct margin in gallbladder and bile duct carcinoma may be inconsistent in 25% of patients due to overdiagnosis of frozen section or new recognition of cancer cells by permanent histology. In situ carcinoma does not always produce local recurrence, while cancer cells in the subepithelial layer strongly predict occurrence of local recurrence.