Contrast-enhanced ultrasound in differentiating malignant from benign portal vein thrombosis in hepatocellular carcinoma

Portal vein thrombosis(PVT) may occur in liver cirrhosis patients. Malignant PVT is a common complication in cirrhotic patients with concomitant hepatocellular carcinoma(HCC) and, in some cases, it may be even the initial sign of an undetected HCC. Detection of malignant PVT in a patient with liver cirrhosis heavily affects the therapeutic strategy. Gray-scale ultrasound(US) is widely unreliable for differentiating benign and malignant thrombi. Although effective for this differential diagnosis, fine-needle biopsy remains an invasive technique. Sensitivity of color-doppler US in detection of malignant thrombi is highly dependent on the size of the thrombus. Contrast-enhanced computed tomography(CT) and contrast-enhanced magnetic resonance(MRI) can be useful to assess the nature of portal thrombus, while limited data are currently available about the role of positron emission tomography(PET) and PET-CT. In contrast with CT, MRI, PET, and PET-CT, contrast-enhanced ultrasound(CEUS) is a fast, effective, well tolerated and cheap technique, that can be performed even in the same session in which the thrombus has been detected. CEUS can be performed bedside and can be available also in transplanted patients. Moreover, CT and MRI only yield a snapshot analysis during contrast diffusion, while CEUS allows for a continuous real-time imaging of the microcirculation that lasts several minutes, so that the whole arterial phase and the late parenchymal phase of the contrast diffusion can be analyzed continuously by real-time US scanning. Continuous real-time monitoring of contrast diffusion entails an easy detection of thrombus maximum enhancement. Moreover, continuous quantitative analyses of enhancement(wash in- wash out studies) by CEUS during contrast diffusion is nowadays available in most CEUS machines, thus giving a more sophisticated and accurate evaluation of the contrast distribution and an increased confidence in diagnosis in difficult cases. In conclusion, CEUS is avery reliable technique with a high intrinsic sensitivity for portal vein patency assessment. More expensive and sophisticated techniques(i.e., CT, MRI, PET, and PET-CT) should only be indicated in undetermined cases at CEUS.

Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease:Potential mechanistic pathways

Although hepatocellular carcinoma(HCC) primarily arises in the background of liver cirrhosis,the development of HCC in nonalcoholic fatty liver disease(NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome(MS) along with obesity and insulin resistance(IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS,NAFLD,and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6,leptin and resistin,as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver,which precede HCC development. Nevertheless,further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.

Non alcoholic steatohepatitis a precursor for hepatocellular carcinoma development

Hepatocellular carcinoma(HCC) is increasing in prevalence and is one of the most common cancers in the world. Chief amongst the risks of attaining HCC are hepatitis B and C infection, aflatoxin B1 ingestion, alcoholism and obesity. The later has been shown to promote non alcoholic fatty liver disease, which can lead to the inflammatory form non alcoholic steatohepatitis(NASH). NASH is a complex metabolic disorder that can impact greatly on hepatic function. The mechanisms by which NASH promotes HCC are only beginning to be characterized. Here in this review, we give an overview of the recent novel mechanisms published that have been associated with NASH and subsequent HCC progression. We will focus our discussion on inflammation and gut derived inflammation and how they contribute to NASH driven HCC.

Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development

AIM: To investigate factors that accurately predict hepatocellular carcinoma(HCC) development after antiviral therapy in chronic hepatitis C(CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein(AFP) to predict HCC development after interferon(IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response(SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/m L before therapy and in non-SVR patients showing AFP ≥ 5 ng/m L before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/m L before therapy and no decrease in AFP to < 5 ng/m L 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/m L before therapy and decreased AFP(P = 0.043). AFP ≥ 5 ng/m L before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase(ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/m L before therapy than in those showing AFP ≥ 5 ng/m L.CONCLUSION: The criteria of AFP < 5 ng/m L before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.

Optimal surveillance program for hepatocellular carcinoma- getting ready, but not yet

Hepatocellular carcinoma(HCC) secondary to chronic viral hepatitis is a major health problem in AsianPacific regions due to the endemics of chronic hepatitis B and C virus infection. HCC surveillance has been recommended to patients who are at risk to develop HCC. Unfortunately, a significant proportion of patients still died in long run due to tumor recurrence. The key components of an optimal surveillance program include an accurate tumor biomarker and optimal surveillance interval. Serum alpha-fetoprotein(AFP), despite of being the most widely used biomarker for HCC surveillance, it was criticized as neither sensitive nor specific. Other HCC biomarkers, including lectin-reactive AFP(AFP-L3), des-gamma carboxyprothrombin, are still under investigations. Recent study showed cancerassociated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing to be accurate with both sensitivity and specificity close to 90% in detecting HCC in a case-control study. Concerning the optimal surveillance interval, we believe one size does not fit all patients. Accurate risk prediction to assist prognostication with well-validated HCC risk scores would be useful to decide the need for HCC surveillance. These key components of an optimal HCC surveillance program should be further validated at a surveillance setting.

Transcriptome analysis elucidates key changes of pleon in the process of carcinization

When megalopa molting to the first juvenile crab stage,the crabs undergo carcinization morphogenesis.To study the key physiological and morphological processes in carcinization,we performed a comparative transcriptomic analysis between the cephalothoraxes and the pleons of megalopa and the first juvenile crab stage in Chinese mitten crab.The results reveal that the major physiological and morphological changes in the pleon were related to energy metabolism(oxidative phosphorylation and AMPK pathways),ventral nerve cord fusion(apoptosis-related pathways),and metamorphosis(transcription factors,Hedgehog and Hippo pathways).We also discovered that the key Hox genes abdominal-B and abdominal-A might regulate morphological changes,especially in the degeneration of the fifth pair of pleopods,and ganglion fusion,respectively.Studying the regulatory mechanisms of carcinization may help us better understand the developmental biology of the juvenile crabs.

Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR:A systematic literature review

AIM:To review literature on efficacy and safety of octreotide-long-acting repeatable(LAR)used at doses higher than the Food and Drug Administration(FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors(NETs).METHODS:We searched Pub Med and Cochrane Library from 1998-2012,5 conferences(American Society of Clinical Oncology,Endocrine Society,European Neuroendocrine Tumor Society,European Society for Medical Oncology,North American Neuroendocrine Tumor Society)from 2000-2013 using Me SH and keyterms including neuroendocrine tumors,carcinoid tumor,carcinoma,neuroendocrine,and octreotide.Bibliographies of accepted articles were also searched.Two reviewers reviewed titles,abstracts,and full-length articles.Studies that reported data on efficacy and safety of≥30 mg/mo octreotide-LAR for NETs in human subjects,published in any language were included in the review.RESULTS:The search identified 1086 publications,of which 238 underwent full-text review(20 were translated into English);17 were included in the review.Studies varied in designs,subjects,octreotide-LAR regimens,and definition of outcomes.Eleven studies reported use of higher doses to control symptoms and tumor progression,although symptom severity and formal quality-of-life analysis were not quantitatively measured.Ten studies reported efficacy,describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/mo.Eight studies reported expert clinical opinion that supported dose escalation of octreotide-LAR up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor progression.Eight studies reported safety;there was no evidence of increased toxicity associated with doses of octreotide-LAR>30 mg/mo.CONCLUSION:As reported in this review,octreotide-LAR at doses>30 mg/mo is being prescribed for symptom and tumor control in NET patients.Furthermore,expert clinical opinion provided support for escalation of somatostatin analogs for refractory hormonal symptoms.

碱性成纤维细胞生长因子在前列腺增生和癌组织中表达的临床意义

目的 :探讨碱性成纤维细胞生长因子 (b FGF)在前列腺增生和前列腺癌组织中表达的临床意义。方法 :采用斑点杂交技术和免疫组化染色 ,测定 40例正常前列腺 (NP)、3 8例前列腺增生症 (BPH )和 3 6例前列腺癌组织 (Pca)中b FGF的表达。结果 :BPH和Pca组织中 ,b FGF的表达明显高于NP组织 (P <0 .0 1)。b FGF表达升高的程度与BPH的分度、Pca的病理分级和临床分期均无明显关系。结论 :b FGF可能为BPH和Pca组织自身分泌 。

TCT联合HPV-DNA在宫颈癌前病变及宫颈癌的诊断价值及P16、Ki67检测的临床意义

目的探讨液基薄层细胞学检查(TCT)联合人乳头瘤病毒DNA(HPV-DNA)在宫颈癌前病变(CIN)及宫颈癌的诊断价值及P16、Ki67的表达及其临床意义。方法将2019年12月至2021年8月苏州大学附属第一医院妇科接诊且自愿加入早期宫颈癌筛查的998例成年女性纳入前瞻性研究,均接受TCT与HPV-DNA检查,两项结果有一项为阳性者行阴道镜下病理活检及宫颈脱落细胞P16、Ki67检测。以病理结果为金标准,比较HPV-DNA、TCT单一检测与联合检测在宫颈病变筛查阳性率的差异,并分析P16、Ki67表达情况。结果998例女性通过HPV-DNA检查筛出178例阳性患者(17.8%),通过TCT检查筛出159例阳性(15.9%),共计有224例女性至少一项检查为阳性(22.4%),224例患者经阴道镜下病理活检,68例检测结果为阳性(6.81%),其中,LSIL 28例(2.81%),HSIL 35例(3.51%),宫颈癌5例(0.50%),宫颈炎最多,有156例(15.6%)。TCT联合HPV-DNA检查与病理活检结果一致性较高,联合检测阳性率显著高于HPV-DNA、TCT单一检查,差异有统计学意义(P<0.05)。宫颈组织中CIN分期越高,P16、Ki67阳性表达率同步升高,差异均有统计学意义(P<0.05)。结论TCT联合HPV-DNA检查在CIN与宫颈癌鉴别诊断中具有重要意义,且P16、Ki67的表达水平与宫颈病变密切相关。

ATM蛋白在不同放射敏感性鼻咽癌细胞株中的表达

背景与目的:ATM(Ataxia-telangiectasiamutant)蛋白与细胞放射敏感性密切相关。本研究探讨ATM蛋白在具有不同放射敏感性的鼻咽癌细胞系CNE1,CNE2中的表达。方法:采用免疫荧光标记技术,对CNE1、CNE2中的ATM蛋白进行激光扫描共聚焦显微镜(LSCM)分析。结果:ATM蛋白定位于细胞核及胞浆中,并以细胞核为主,且CNE1细胞核中ATM蛋白阳性细胞的荧光强度较CNE2强;半定量分析,CNE1中ATM蛋白表达的积分吸光度值为9×106,CNE2中为3×106。结论:ATM蛋白的表达在CNE1、CNE2中有差别,这种差别可能与它们所具有的不同放射敏感性有关。

氟比洛芬酯脂微球载体制剂与注射用酮洛芬对照治疗术后及癌性疼痛

目的：观察氟比洛芬酯与酮洛芬对照治疗术后及癌性疼痛患者的有效性。方法：日本36家医院共入选腹部术后患者224例，癌性疼痛患者163例，随机分为氟比洛芬酯组192例与酮洛芬组195例，分别用氟比洛芬酯与酮洛芬安慰剂和酮洛芬与氟比洛芬酯安慰剂。氟比洛芬酯及其安慰剂5mL静脉内注射，酮洛芬及其安慰剂每瓶用2．5mL溶液溶解臀部肌内注射。结果：可评价病例氟比洛芬酯组对术后疼痛111例患者改善率为73．9％，高于酮洛芬组(n=109)的66．1％，但2组差异无显著性(P>0．05)；药效持续时间氟比洛芬酯组比酮洛芬组延长(P<0．05)。氟比洛芬酯组癌性疼痛(n=77)改善率为77％，高于酮洛芬组(n=81)的59．3％(P>0．05)，药效持续时间氟比洛芬酯组比酮洛芬组延长(P<0．05)。结论：在治疗术后疼痛和癌性疼痛时，氟比洛芬酯的疗效与酮洛芬相近，但镇痛时间明显延长。

内镜下支架介入治疗晚期食管癌癌性梗阻临床疗效评价

目的评价内镜下放置覆膜食管支架治疗晚期食管癌癌性梗阻的临床疗效。方法选择晚期食管癌癌性梗阻218例为治疗组,同期放弃内镜介入治疗的晚期食管癌癌性梗阻30例为未治疗组,在内镜介导下对治疗组癌性狭窄放置覆膜支架。术后随访观察支架置入成功率、梗阻改善状况及生存期。结果治疗组112例支架成功植入,成功率为97.25%。治疗组6月、12月和18月的累积生存率分别为97%、88.5%、68%,未治疗组6月、12月和18月的累积生存率分别为51%、33.7%和21.4%。结论内镜下放置覆膜支架是治疗晚期食管癌理想的方法之一,能最大程度地解决癌性梗阻,提高患者的生存质量。

胃癌中内分泌细胞与癌分化程度的关系

利用11例胃类癌和13例胃低、未分化癌的切除标本,探讨内分泌细胞出现的数量与胃癌类型和分化程度的关系。切片均作了嗜银、亲银组化染色,并用4种神经内分泌抗血清(胃泌素、生长抑素、胰多肽、血清素)PAP法免疫组化染色,4例作了电镜检查。结果胃类癌每例至少一项阳性,其中4例电镜证实有神经分泌颗粒;低、未分化癌组多数病例各项检查阴性,但4例不同阳性结果,其中2例阳性细胞数超过50%,可称内分泌细胞癌。表明肿瘤愈原始,愈多向分化。最后对胃癌中内分泌细胞与癌分化程度的关系,以及胃类癌和胃内分泌细胞癌的特征、名称和组织发生进行了讨论。

胰腺导管上皮细胞与胰腺癌细胞内β-葡萄糖醛酸酶免疫电镜定位研究

目的：观测β－葡萄糖醛酸酶（β－Ｇｌｕｃｕｒｏｎｉｄａｓｅ，β－Ｇ）在人体胰腺导管上皮细胞与胰腺癌细胞中的定位，探索良、恶两种细胞内β－Ｇ的差异。方法：采用低温包埋，紫外线照射，超薄切片，胶体金标记，免疫电镜方法。结果：β－Ｇ定位于内质网和溶酶体内，同时观察到胰腺癌细胞中标记β－Ｇ的金颗粒数目明显多于胰腺导管上皮细胞中金颗粒数目。结论：癌细胞分泌β－Ｇ增多，对胰腺癌的早期发现、早期诊断有一定意义。

Advances in non-surgical management of primary liver cancer

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC.

癌症疼痛的家居宁养医疗护理

目的 探讨完善宁养院家居医疗护理。方法 采用来诊接诊、家居探访、电话咨询方式 ,科学评估病情 ,合理镇痛治疗。指导、辅助家属做好家居医疗护理。重视心理纾缓治疗。随时了解病人病情及生活质量 ,及时做出正确调整 ,同时认真登记建档及严格麻醉药管理 ,完善医疗护理管理。结果 患者癌痛镇痛效果和生活质量明显改善。结论 家居宁养医疗护理能满足大多数癌痛患者的大部分医疗护理需求 。

氟比洛芬酯脂微球注射液对老年癌痛镇痛作用的临床分析

目的观察氟比洛芬酯脂微球载体注射液(商品名凯纷)治疗老年癌痛的疗效和副作用。方法 47例不能耐受阿片类药物或阿片类药物效果不佳的癌性疼痛患在2周的时间内者每天静脉注射50～100 mg氟比洛芬酯脂微球载体注射液,分别就其疗效、生活质量改善情况以及不良反应等方面进行全面评价。结果氟比洛芬酯脂微球载体注射液治疗老年癌痛的有效率为87.23%(PR+CR),生活质量改善情况治疗前后差异有统计学意义(P<0.05)。但未见一般非甾体类药物常见腹痛、消化道出血等副作用;也未见便秘、恶心、呕吐、嗜睡、血压下降等阿片类药物常见不良反应。结论氟比洛芬酩脂微球载体注射液治疗老年癌痛疗效可靠,生活质量可得到改善,氟比洛芬酯脂微球载体注射液不良反应发生率较低,为临床止痛药物的选择提供了一个新途径。

鼻咽结核及其合并鼻咽癌的诊治体会

目的探讨鼻咽结核合并鼻咽癌的临床特征,提高认识,减少误诊.方法对自1984年3月～2004年1月,我们诊治的6例鼻咽结核合并鼻咽癌和20例鼻咽结核患者的临床资料进行分析.结果鼻咽结核组:①年轻;②颈淋巴结偏小、多个,多双侧,常融合成串,质地中,可活动;③耳、鼻症状少;④无颅神经损害;⑤EB病毒VCA-IgA抗体滴度测定阴性;⑥病变部位均在顶壁是其特点;⑦咽痛(12/20)和颈酸痛(13/20)可能又是鼻咽和颈淋巴结结核特有的临床症状.鼻咽结核合并鼻咽癌组:①中年居多;②颈淋巴结较大,质地硬,固定;③多有耳、鼻症状;④常伴颅神经损害;⑤EB病毒VCA-IgA抗体滴度测定阳性;⑥50%(3/6例)患者初诊误诊为鼻咽结核.结论鼻咽结核合并鼻咽癌易误诊,临床医师应提高警觉,与鼻咽结核的鉴别诊断除临床表现外,需做活检在病理上给予确诊,EB病毒VCA-IgA抗体滴度测定有重要的鉴别诊断价值.误诊会降低存活率.

ADA、CEA、CA对癌性与结核性胸水的鉴别

目的 探讨腺苷脱氨酶 (adnosinedeaminase ,ADA)、癌胚抗原 (carcinoembryonicantigen ,CEA)、糖类抗原(carbohydrateantigen ,CA)对癌性与结核性胸水的鉴别意义。 方法 对 3年来确诊的结核性胸水 5 3例、癌性胸液 43例患者的胸水标本进行检测。结果 在结核性胸液中 ,ADA均值显著高于其在癌性胸水中的均值 (P <0 .0 1) ,而且检测的敏感性、特异性和准确性较其他指标均高 (P <0 .0 1)。在癌性胸液中 ,CEA、CA5 0、CA12 5、CA199、CA2 11的均值较它们在结核性胸液中的均值显著升高 (P <0 .0 1,P <0 .0 5 )。结论 在癌性与结核性胸水的鉴别中 ,对ADA和CA2 11的联合检测 。

基于SOX9的生物学研究及其在肝癌干细胞中的研究进展

肿瘤干细胞是指在肿瘤组织中高度恶性的细胞亚群,具有高侵袭性、易转移性、多耐药性特点,与肿瘤复发密切相关。因此,肿瘤干细胞可能成为未来肿瘤治疗的靶点。目前发现的肿瘤干细胞标志物包括CD133、CD90、CD44等。SOX9(sex determining region Y box-9)除了参与多个器官的生长发育外,还与组织纤维化及肿瘤的发生有着密切关系,尤其在多种肿瘤干细胞中高表达。SOX9亦在肝癌干细胞中高表达,并通过相关信号通路影响肝癌干细胞的自我更新、增殖以及耐药,因此成为肝癌潜在的预后判断指标和治疗靶点。