结直肠癌肝转移组织中胸苷磷酸化酶表达

目的 检测胸苷磷酸化酶(TP)在人结直肠癌肝转移组织中的表达,分析该表达与肿瘤相关巨噬细胞(TAM)及与患者预后的相关性.方法 采用抗TP的单克隆抗体654-1及1C6-203、抗巨噬细胞标记物cD68的单克隆抗体PG-M1,对28例人结直肠癌肝转移标本进行免疫组织化学染色分析,对3种抗体阳性细胞进行细胞计数,计算各种阳性细胞之间,以及各种阳性细胞与患者预后的相关性.结果 28例标本中,转移癌细胞表达TP甲阳性的仅2例,癌组织中表达TP的阳性细胞主要是癌巢周围的间质细胞,特别是肿瘤相关巨噬细胞(TAM).通过对3种阳性细胞计数发现,2种TP抗体染色阳性细胞数相关(r=0.697,P<0.01);654-1阳性细胞数与TAM细胞数相关(r=0.703,P<0.01);而1C6-203阳性细胞数与TAM细胞数相关较弱,无统计学意义(r=0.359,P=0.06).16例死亡患者的术后生存时间与3种阳性细胞数目均无相关(P>0.05).结论 在人结直肠癌肝转移组织中表达TP阳性的细胞主要是TAM,组织中TP阳性细胞及CD68阳性巨噬细胞的多少与患者预后生存的时间无相关.     

Serum vascular endothelial growth factor-C and lymphoangiogenesis are associated with the lymph node metastasis and prognosis of patients with colorectal cancer

Background: The study aims to investigate the relationship among serum vascular endothelial growth factor (SVEGF‐C), VEGF‐C expression and lymph vessel density (LVD) in tumour tissue, and their influence to colorectal carcinoma (CRC). Methods: The SVEGF‐C concentration of 110 patients with CRC and 40 healthy donors was examined by ELISA. The 110 tumour tissues and 40 normal colorectal specimens were examined by immunohistochemical staining (SP method) with VEGF‐C and podoplanin (lymphatic vessel specific antibody). Kaplan–Meier survival analysis determined the influence on CRC prognosis. Results: CRC SVEGF‐C level (889.0 ± 264.0 pg/mL) significantly exceeded (P= 0.000) the control level (373.2 ± 97.3 ng/L), and was significantly higher in T3, lymph node metastasis (LNM), distant metastasis, and pTNM groups III and IV. LNM prediction sensitivity, specificity, and accuracy of SVEGF‐C were 85.7, 80.0 and 83.6%, respectively (875 pg/mL cut‐off). VEGF‐C expression was elevated in CRC versus control patients (P= 0.000), and was significantly related to LNM and pTNM stages III and IV. Mean LVD in CRC (6.3 ± 0.7/200 HP) significantly exceeded control mean (3.0 ± 0.7/200 HP) (P= 0.000). LVD was significantly higher in LNM and pTNM stages III and IV. SVEGF‐C level was significantly higher in VEGF‐C positive versus negative patients (P= 0.000), and was related to LVD (P= 0.009). Kaplan–Meier ranking of prognostic factors was SVEGF‐C level (P= 0.000), VEGF‐C expression (P= 0.001) and LVD (P= 0.012). Conclusion: SVEGF‐C level, VEGF‐C and LVD are related to LNM and poor prognosis in patients with CRC. SVEGF‐C may be a biomarker for LNM in CRC.     

Effects of caustic lye injury to the esophageal smooth muscle reactivity: in vitro study

PURPOSE: We investigated late effects of caustic lye injury on esophageal smooth muscle reactivity in the rat model. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into two groups. Through a median laparatomy incision, abdominal esophageal segment was isolated. Orogastric and gastric (via gastrotomy) catheters were placed and tied over the isolated esophageal segment. Saline (0.9%) or 50% sodium hydroxide (1 ml) solution were instilled via orogastric catheter to the isolated segment in the control and caustic esophagus (CE group) groups, respectively. Then, the esophagus was rinsed with 0.9% saline via gastric catheter. The esophagus was removed and studied in organ chambers 28 days after the operation. RESULTS: Carbachol- and KCl-induced contractile responses of esophageal smooth muscle were significantly reduced in the CE group with decreased E(max) value compared with the control group. Relaxant responses to serotonin were significantly reduced in the CE group with decreased E(max) value compared with the control group. No significant differences were found in E(max) and pD(2) values for papaverine acting on esophageal strips from the two groups. CONCLUSION: The results provide evidence that, a surgically created caustic injury causes impaired smooth muscle reactivity that may contribute to esophageal motor dysfunction.     

The neurosurgical management of brain metastasis from colorectal cancer: A report of three cases

We report herein three cases of brain metastasis from primary colorectal cancer in which the metastatic lesion was resected to effectively relieve neurological symptoms. Case 1 was a 61-year-old woman with a solitary brain metastasis from colorectal cancer and no other metastases; case 2 was a 59-year-old woman who died from liver metastasis 11 months after resection of the metastatic brain tumor; and case 3 was a 68-year-old woman with multiple metastases to the lungs and bones detected before the brain metastasis. According to 16 cases previously reported in the Japanese literature and our 3 cases, the interval between diagnosis of the primary cancer and discovery of brain metastasis was 23 months on average, while the median survival after the discovery of brain metastasis was 7 months. Brain metastases with liver and lung metastases were seen more frequently than brain metastases alone. In these three cases, chemotherapy appears to have been of no use in preventing recurrence. Thus, we believe neurosurgical management to be appropriate for a solitary lesion and that it should be actively pursued to prolong survival and improve quality of life.     

结直肠癌肝转移的分子机制研究进展

目的对近年来国内外就结直肠癌肝转移的分子机制研究进展的文献进行总结,旨在为结直肠癌肝转移的诊治及研究提供帮助。方法复习近年来国内外针对结直肠癌肝转移的文献并进行综述。结果影响结直肠癌肝转移的分子机制复杂,如microRNA-192可通过多个靶点抑制结直肠癌肝转移,microRNA-181a则可以促进结直肠癌肝转移。转化生长因子β(Transforming growth factor beta,TGF-β)通过抑制细胞增殖和Smad依赖性信号传导诱导细胞凋亡,起到抑制肿瘤生长的作用。CEA水平的升高不仅对结直肠癌的诊断提供帮助,作为结直肠癌患者的预后指标,CEA还影响结直肠癌细胞在血管中的存活、改变肝脏微环境以及循环肿瘤细胞在肝脏中的黏附和存活,促进肝转移。结论结直肠癌肝转移的分子机制尚未完全阐明,通过对结直肠癌肝转移机制的深入研究,可为结直肠癌肝转移提供分子靶向治疗靶点,如贝伐单抗、西妥昔单抗、帕尼单抗等。检测结直肠癌患者血清学CEA的变化,可以有助于结直肠癌的诊断、判断复发和预后以及转移情况。     

Hemodynamics in a compliant hydraulic in vitro model of straight versus tapered PTFE arteriovenous graft

BACKGROUND: Hemodialysis patients require a vascular access to deliver sufficient blood flow to the artificial kidney. Of these vascular accesses, 30% are prosthetic (mainly polytetrafluorethylene [PTFE]) graft implants. These grafts are prone to the development of stenosis in the vein due to intimal hyperplasia, subsequently leading to thrombosis and graft failure. AIM: We investigated the hemodynamics in a straight and a tapered PTFE-graft and compare the hydrodynamical behavior of both grafts. MATERIALS AND METHODS: Two different vascular access geometry models were examined: a 6-mm diameter straight graft and a 4- to 7-mm tapered graft. The grafts were sutured to a compliant silicon model of an artery and vein in a loop configuration. Flow rate varied between 500 and 1500 mL/min. Two conditions were tested: 1). control: mean pressure is 100 mm Hg at the arterial inlet; and 2). low resistance condition: pressure is 20 mm Hg at the venous outlet. Pulse pressure is 60 mm Hg at the arterial inlet for both conditions. Pressure and flow velocity are measured continuously, while flow rate is measured volumetrically. RESULTS: The pressure drop at the arterial anastomosis of the tapered graft is three times higher compared to the straight graft model. Intragraft pressure drops are similar in both graft types. Mean pressure and pulse pressure in the graft and vein are decreased in the low resistance condition. Also, the difference between maximum and minimum velocity is smaller in this. CONCLUSIONS: No significant differences are noted between the graft geometries: pressure drop over the graft is almost equal. The major difference is the higher pressure drop at the arterial anastomosis of the tapered graft.     

去整合素蛋白酶23在结直肠癌肝转移中的表达及意义

目的 探讨抑癌基因去整合素蛋白酶23（ADAM23）的表达与结直肠癌肝转移发生发展的关系.方法 应用免疫组织化学和荧光实时定量PCR方法 分析31例结直肠癌患者的癌组织、肝转移灶组织和正常结直肠黏膜组织中的ADAM23蛋白和mRNA表达情况.结果 ADAM23蛋白和mRNA在结直肠癌组织和肝转移癌组织中的表达明显低于正常结直肠癌黏膜组织（P〈0.05）;肝转移癌组织中ADAM23蛋白和mRNA的表达明显低于结直肠癌组织（P〈0.05）.结论 ADAM23的异常表达可能在结直肠癌及其肝转移的发生发展中起重要作用.     

结直肠癌脑转移诊治研究进展

目的阐述结直肠癌脑转移患者的临床病理特征,综述其诊断和治疗进展,为我国结直肠癌脑转移患者的全程管理提供参考。方法对结直肠癌脑转移的最新研究结果和既往文献进行综述。结果结直肠癌脑转移患者预后较差,其分子病理机制复杂多样,已发现一些与结直肠癌脑转移发生相关的危险因素。结直肠癌脑转移的典型影像学特征有助于对其诊断。目前,放射治疗仍然是结直肠癌脑转移患者的主要治疗手段,贝伐珠单抗治疗、免疫治疗联合放射治疗有望提高结直肠癌脑转移患者的生存率及延长生存期。结论科学规范的预防和诊治有利于降低结直肠癌脑转移发病率和提高患者生存率。     

Impaired gastric motility in the gastroesophageal reflux rat model: an in vitro study

PURPOSE: The present study investigated the effects of acid and mixed reflux on the responsiveness of gastric smooth muscle in the gastroesophageal reflux (GER) rat model. MATERIAL AND METHODS: Three groups of rat were studied encompassing acid reflux, mixed reflux and sham operation. Acid reflux was induced by pyloric ligation (AR group) and mixed reflux was induced by jejunal ligation 1 cm distal to Treitz ligament (MR group). Similar surgical manipulations were carried out in the sham operated rats (SO group). Carbachol-, serotonin-, KCl-induced contractile response and nicotine-, sodium nitroprusside-, papaverine-induced relaxant response in isolated gastric fundus smooth muscle strips were determined using in vitro muscle technique 24 h after surgery. RESULTS: Isolated gastric fundus smooth muscle contractility to serotonin, carbachol or KCl was significantly reduced in the AR and MR groups with decreased Emax and pD(2) values compared with the SO group. Relaxant responses to nicotine was significantly increased in the AR and MR groups with increased Emax and pD(2) values compared with the SO group. Sodium nitroprusside and papaverine-induced-relaxant responses were similar in all of the groups and there was no change in agonist potency. CONCLUSION: The present study indicates that decreased contractile and increased nicotine-induced relaxant response of the gastric smooth muscle in the surgically created GER model. These findings suggest that impaired gastric smooth muscle reactivity at least in part may play a role in gastric dysmotility in GER.     

CSE1L modulates Ras-induced cancer cell invasion: correlation of K-Ras mutation and CSE1L expression in colorectal cancer progression

Background

Ras plays an important role in colorectal cancer progression. CSE1L (chromosome segregation 1-like) gene maps to 20q13, a chromosomal region that correlates with colorectal cancer development. We investigated the association of CSE1L with Ras in colorectal cancer progression.

Methods

The effect of CSE1L on metastasis-stimulating activity of Ras was studied in an animal model with tumor cells expressing CSE1L-specific shRNA and v-H-Ras. CSE1L expression was evaluated by the immunohistochemical analysis of 127 surgically resected colorectal tumors. K-Ras mutations were analyzed by direct sequencing.

Results

CSE1L knockdown reduced Ras-induced metastasis of B16F10 melanoma cells in C57BL/6 mice. v-H-Ras expression altered the cellular trafficking of CSE1L and increased CSE1L secretion. Most colorectal tumors were positive for CSE1L staining (98.4%, 125 of 127). Colorectal tumors with K-Ras mutation or high cytoplasmic CSE1L expression were correlated with T status (depth of tumor penetration; P = .004), stage (P = .004), and lymph node metastasis (P = .019).

Conclusions

CSE1L may be a target for treating Ras-associated tumors. Analysis of K-Ras mutation and CSE1L expression may provide valuable clinical and pathological information to aid in the determination of treatment options for colorectal cancer.     

乳腺癌癌周淋巴管密度对腋淋巴结转移状态的影响

目的探讨乳腺癌患者癌周组织中淋巴管密度（1ymphaticvesseldensity,LVD）与同侧腋淋巴结转移数量及转移水平的关系。方法对接受乳腺癌改良根治术的浸润性乳腺癌95例,采用D2—40单克隆抗体免疫组织化学法检测乳腺癌癌灶周边组织微淋巴管,计数LVD,分析其与同侧乳腺癌腋淋巴结转移的关系。结果95例乳腺癌癌周组织LVD与腋淋巴结转移数量呈正相关（r=0．856）,与腋淋巴结转移水平亦有显著相关性（r=0．664）。结论乳腺癌组织中癌周淋巴管密度与乳腺癌的淋巴结转移数目及淋巴结转移水平密切相关。     

Inhibitory effects of prostaglandin D2 against the proliferation of human colon cancer cell lines and hepatic metastasis from colorectal cancer

The inhibitory action of prostaglandin D₂ (PGD₂) and its effect on the cell cycle were examined in cell lines SW480 and LS174T of human colon cancer. The growth of the cell lines were assessed 24h and 48h after the addition of 1.0μg/ml and 10.0μg/ml PGD₂. The growth of SW480 cells and 24h and 48h after the addition of 10.0μ/ml, while that of LS174T was inhibited by both doses after 24h and 48h. S-Phase DNA synthesis in the SW480 cells was significantly blocked 24h after the addition of 10.0μg/ml PGD₂. The cell cycle of LS174T cells was arrested at the G₀+G₁ phase 24h after the addition of 1.0μg/ml and 10.0μg/ml PGD₂. The correlation between hepatic metastasis and PGD₂ concentration in human cancer tissue was examined. The mean value of PGD₂ concentrations in the primary cancer tissue was significantly lower in the hepatic metastasis group than that in the group without hepatic metastasis. These findings suggest that measuring the PGD₂ in cancer tissue may be useful for detecting and predicting the hepatic metastasis from human colorectal cancer.     

A novel model of pneumonia from intraperitoneal injection of bacteria

BACKGROUND: Pneumonia remains a major clinical problem in the surgical patient. Experimental modeling by intratracheal injection of bacteria is not consistently reproducible. In an attempt to produce peritonitis by Klebsiella, we found evidence of pneumonia on autopsy and further developed this approach as a new experimental model. METHODS: Male Swiss Webster mice were given intraperitoneal (IP) injections of Klebsiella pneumoniae serotype 2 in different doses and this was compared with similar doses given intravenously (IV). A dose dependent survival curve was generated. Subsequently, 10(3) colony forming units (CFU) of bacteria were used in further experiments. Blood, peritoneal fluid and lung tissue were collected at time points up to 72 hours after injection and were cultured for levels of bacteria. Lung weights and myeloperoxidase levels were also measured. RESULTS: Intraperitoneal administration of Klebsiella was uniformly lethal with as few as 10(2) bacteria. Lung weight increased after IP Klebsiella, and all animals became bacteremic within 24 hours correlating with high bacterial levels in the lung. Conversely, most animals (72%) survived IV injection of bacteria, and were able to clear bacteria from the blood and lung. CONCLUSIONS: We found that this model produced no clinically apparent peritonitis after 48 hours, but uniformly resulted in histopathologic changes of pneumonia by 24 hours. Survival time was related to initial dose of Klebsiella and there was a linear correlation between bacterial levels in the blood and lung. This model is reproducible, simple to perform, and the severity is easy to manipulate.     

Prognostic factors in survival of colorectal cancer patients with synchronous liver metastasis

Aim To determine the factors affecting the survival in colorectal cancer patients with synchronous liver metastases. Method A total of 168 patients who had been treated colorectal cancer with synchronous liver metastases at Guangxi Medical University from January 2000 to December 2005 were identified. Criteria studied consisted of gender, age, time of symptoms, primary tumour location, primary tumour circumference, histological type, grade (tumour differentiation), T‐status, N‐status, large bowel obstruction, type of operation, primary tumour resection, ascities, location, number and diameter of liver lesions, preoperative CEA and chemotherapy. Survival curves were plotted using the Kaplan–Meier method. Multivariate analysis was conducted by Cox regression analysis. Results The mean survival time for all patients was 18.71 (SEM = 1.59) months. The 1, 2, 3 and 5‐year survival rates were 55.95%, 23.21%, 12.30%, 8.0% respectively. Univariate analysis share of grade (tumour differentiation), N‐status, large bowel obstruction, operation, primary tumour resection, location, number and the most diameter of liver lesions, extrahepatic transfer, preoperative CEA level and chemotherapy to be predictors of survival. In the Cox regression analysis, the N‐status, large bowel obstruction, operation, diameter of liver lesion and extrahepatic transfer were independent factors related to survival. Conclusion Tumour differentiation, N‐status, bowel obstruction, operation, primary tumour resection, location of liver metastasis, number of liver metastasis, diameter of liver metastasis, extrahepatic transfer, preoperative CEA level and chemotherapy are related to the survival of patients with colorectal cancer and synchronous liver metastases.     

一种诊断结直肠癌患者淋巴结转移的新方法

结直肠癌的预后判断主要根据有确切资料的病理学分期、原发灶浸润深度、分化程度和微血管侵犯的组织学结果,术后3～7 d就能得出结果.但传统的淋巴结检查方法中,淋巴结转移数目和转移淋巴结解剖部位结果常因工作量巨大,旷日持久,不能得出结果.结直肠癌患者术后医患双方都要求及早确定分期,用以确定辅助化疗,治疗过度或治疗不足皆对病人有害,是无证据、不负责且不规范的治疗.当今国外有研究局部淋巴结转移与淋巴结浸出液癌胚抗原(carcinoembryonic,CEA)浓度密切相关,并能简捷、快速得出结果,有待成为一种诊断结直肠癌淋巴结转移的新方法.     

乳腺癌组织中COX-2、VEGF-C表达与淋巴转移的相关性研究

目的 探讨COX-2、VEGF-C在人乳腺癌组织中的表达及其与淋巴转移之间的关系.方法 运用免疫组织化学SABC法检测COX-2和VEGF-C在乳腺癌组织中的表达情况.结果 60例乳腺癌组织中COX-2和VEGF-C的表达阳性率分别为66.7%和60.0%,且二者表达呈正相关(r=0.429,P<0.05).COX-2阳性、VEGF-C阳性组淋巴转移的发生率(80.0%)明显高于COX-2阴性、VEGF-C阴性组(21.4%;P<0.05).结论 COX-2、VEGF-C在乳腺癌组织中呈过表达,呈正相关关系,且与乳腺癌的淋巴转移关系密切,COX-2表达上调可能促使VEGF-C的过表达,诱导肿瘤淋巴管的生成,从而导致乳腺癌细胞淋巴转移的发生.     

The prognostic significance of resection of primary tumor in gastric and colorectal cancer patients with synchronous liver metastasis

The significance of primary tumor resection in gastric and colorectal cancer patients with liver metastasis (H(+)) was evaluated in terms of operative mortality and survival rate by dividing the materials [293 gastric cancer and 80 colorectal cancer patients (53 colon and 27 rectum) with synchronous liver metastasis] into the following groups: Firstly, with or without peritoneal dissemination (P), secondly, with or without resection of the primary tumor and thirdly, with or without postoperative adjuvant chemotherapy. The following results were obtained: (1) The direct operative death rate of primary tumor resection, excluding death from other causes, showed an absence of statistically significant differences between the P₀H(+) and P(+)H(+) gastric and colorectal cancer patients. (2) There was no significance in the prognosis between the primary tumor resection + postoperative chemotherapy group and the non-resectable group in the P(+)H(+) gastric and colorectal cancer patients, revealing no prognostic value of the primary tumor. (3) In the P₀H(+) gastric and colorectal cancer patients, the primary tumor resection + postoperative chemotherapy group was significantly more favorable in prognosis than was the primary tumor resection alone group or the non-resectable group, showing the value of primary tumor resection.