直径<1cm肺腺癌浸润进展影响因素及临床预后探讨

目的:探讨直径<1cm肺浸润性腺癌发生独立影响因素及临床预后。方法回顾性分析我院2013年1月-2018年3月收治直径<1cm肺腺癌患者共364例临床资料,根据胸部影像学特征分组,其中pGGN(A组)122例,mGGN(B组)136例,SN(C组)106例,比较三组基线临床特征和手术相关指标,分析结节直径亚组病理相关指标和分期差异,采用Logistic回归模型评价直径<1cm肺浸润性腺癌发生独立影响因素。结果①364例患者均胸腔镜手术治疗,其中楔形切除,切缘距病灶均<2cm。C组肺叶切除比例显著高于A组、B组(P<0.05);男性吸烟比例显著高于女性(P<0.05);②122例pGGN患者中1~5mm病灶术后病理均为原位/微浸润腺癌;A组6~10mm病灶Ia1期比例显著高于1~5mm病灶(P<0.05)。mGGN中6~10mm病灶共92例,包括胸膜侵犯6例,脉管癌栓2例;SN中6~10mm病灶共78例,包括胸膜侵犯10例,脉管癌栓4例,淋巴结转移4例。③单因素分析结果显示,AIS+MIA和IAC组吸烟史、既往癌症罹患史、病灶影像学特征及病灶直径比较,差异有统计学意义(P<0.05);多因素分析结果显示,吸烟史、既往癌症罹患史、mGGN、SN及病灶直径>5mm,均是直径<1cm肺浸润性腺癌独立危险因素(P<0.05)。④364例患者中肺叶切除术后住院期间因肺栓塞死亡1例,随访时间为20~81个月,中位随访时间为43.0个月;随访过程中Ia1期患者中1例在术后14个月因肺炎死亡;随访总生存率为99.72%(362/363)。结论直径<1cm肺浸润性腺癌患者中mGGN和SN如病灶直径达6~10mm,更易累及胸膜或淋巴结;吸烟史、既往癌症罹患史、mGGN、SN及病灶直径>5mm均与直径<1cm肺浸润性腺癌发生独立相关。     

HRCT在肺单发性磨玻璃样病灶鉴别诊断中的运用价值探析

目的探究高分辨率计算机断层扫描(HRCT)运用于肺单发性磨玻璃样病灶鉴别诊断中的效果。方法选取我院2013年5月至2016年5月接受的肺内磨玻璃密度影(GGO)患者108例,对所有患者给予HRCT诊断,分析HRCT征象在良恶性GGO中的分布及各病理类型的直径、密度情况。结果非典型腺瘤样增生直径均在10mm以内,炎性直径在10-30mm者比率为81.82%,恶性GGO在10-30mm者的比率为82.72%;单纯GGO以非典型腺瘤样增生及炎性为主,恶性GGO以腺癌为主。恶性GGO患者分叶征、毛刺征、血管集束征及胸膜凹陷征的例数分布显著高于良性GGO患者,差异有统计学意义(P0.05);恶性GGO患者的空泡征、支气管充气征例数分布与良性GGO患者间的差异无统计学意义(P0.05)。结论 HRCT在肺单发性磨玻璃样病灶患者中具有较高诊断价值,直径在10mm以上的GGO病变者需给予密切随访。HRCT上表现分叶征、毛刺征、血管集束征及胸膜凹陷征为GGO恶性病变的有效诊断依据,应对出现此类表现者需给予积极治疗。     

肺部磨玻璃结节的CT影像特征评估肺腺癌浸润性的价值

目的探讨肺部磨玻璃结节的电子计算机断层扫描(CT)影像特征,对肺腺癌浸润性的评估价值。方法选取2016年2月-2018年10月来我院经CT扫描和病理检查确诊的62例磨玻璃结节患者,其中分为非浸润性腺癌组(n=34)和浸润性腺癌组(n=28),比较两组CT征象,采用Logistic回归分析法,分析影响肿瘤浸润的危险因素,采用受试者工作特征曲线(ROC)下面积(AUC)比较各危险因素对肺腺癌浸润性的预测价值。结果非浸润性腺癌组的病灶直径、CT值、相对CT值、病灶边缘、空气支气管征、胸膜凹陷征和磨玻璃类型与浸润性腺癌组比较,差异具有统计学意义(P 0. 05); Logistic回归分析显示,病灶直径和空气支气管征可作为评估浸润性腺癌的危险因素(P 0. 05);病灶直径的AUC值明显高于空气支气管征的AUC值(P 0. 05)。结论肺部CT扫描磨玻璃结节的病灶直径,有助于术前预测患者有无浸润性肺腺癌的可能,可用作临床治疗方案选择的参考。     

手术治疗22例单纯性肺磨玻璃样病变

目的总结单纯性肺磨玻璃样病变(pure ground-glass opacity,pGGO)的临床特征,探讨其对早期肺癌的诊断意义与最佳治疗方案。方法收集我科近五年来22例pGGO患者的临床资料,分析患者的临床特性、影像特点、手术方式、病理类型和预后。结果 22例pGGO患者经过保守治疗无效后行手术治疗,术后病理明确12例为原位腺癌,8例为不典型腺瘤样增生,2例为炎性假瘤。原位腺癌直径(14±3)mm,非典型腺瘤样增生病灶直径(8±2)mm,差异有统计学意义(P0.05)。术后随访4个月~5年,患者均生存。结论pGGO中多数原位腺癌病灶直径大于非典型腺瘤样增生病灶。胸部CT提示直径≥10 mm、有恶性征象或含有实性成分的pGGO为早期肺癌或癌前病变,应提高警惕,尽早行胸腔镜下肺叶切除术。     

多层螺旋CT对肺局灶性亚厘米磨玻璃结节的诊断价值

目的探讨多层螺旋CT(MSCT)在肺局灶性亚厘米磨玻璃结节(f GGO)诊断中的临床价值。方法分析95例亚厘米f GGO患者的MSCT检查资料,并与病理诊断结果相对照,比较不同病理类型f GGO病灶大小、内部实性成分大小、混合型磨玻璃结节(m GGO)比例、和胸膜凹陷、病灶形状、分叶、毛刺、空泡和边界情况。按照病灶与周围血管的关系分为3型,分析不同病理类型f GGO与血管关系分型。结果 95例患者病灶最小为4.1 mm,最大为9.9 mm。浸润前组与腺癌组病变大小、实性成分大小、m GGO和分叶征所占比例差异有统计学意义(P0.05),而胸膜凹陷、病灶形状、毛刺、空泡和边界情况差异无统计学意义(P0.05),良性组除分叶所占比例与腺癌组差异有统计学意义外,其余征象与腺癌组差异均无统计学意义(P0.05),按照f GGO与血管关系分型,良性组均为Ⅰ型和Ⅱ型,浸润前组Ⅲ型10例(25.6%),腺癌组Ⅲ型17例(39.5%),浸润前组、腺癌组Ⅲ型所占比例均高于良性组(P0.05)。结论肺内亚厘米f GGO术前定性诊断难度较大,病灶的MSCT形态特点及其与周围血管的关系对病变性质的判断有一定价值。     

肺段切除在早期浸润性肺腺癌中的应用评价

目的探讨亚肺叶切除和肺叶切除在原发浸润性肺腺癌中的预后效果。 方法通过HIS系统(Hospital Information System)选择肿瘤大小在0～2 cm的原发浸润性肺腺癌患者作为研究对象。通过倾向性匹配分析来消除潜在的偏倚,使用Kaplan-Meier生存分析比较亚肺叶切除组和肺叶切除组的总体生存时间。 结果共纳入了154例肿瘤大小为0～2 cm的浸润性肺腺癌患者,其中肺段切除31例,肺叶切除123例,3年生存时间的分析的结果显示：肺段切除的预后和肺叶切除相似(OS: HR, 1.29(0.13-12.81),P＝0.81);154例浸润性腺癌患者术后10例出现并发症,其中肺段切除组1例(3.2%)出现持续漏气(超过7 d);肺叶切除组出现9例,2例出现持续漏气,1例出现肺部感染,2例出现皮下气肿,1例出现胸腔积液。基于年龄、性别、吸烟史、慢性病史、肿瘤大小及淋巴结清扫数目等变量进行倾向性匹配分析获得28对肺段切除和肺叶切除病例,两组的近期总体生存时间无明显统计学差异性(OS: HR, 2.50(0.12-52.20),P＝0.38)。 结论肺段切除可作为早期原发浸润性肺腺癌的可选治疗方法。     

以磨玻璃样密度影为表现的早期肺癌并发肺结核患者的诊治分析

目的 分析以磨玻璃样密度影(ground-glass opacity,GGO)为表现的早期肺癌并发肺结核患者的临床特点,以达到早期识别及治疗的目的。方法 对山东大学附属山东省胸科医院自2013年1月至2018年2月确诊的14例以GGO为首要表现的肺癌并发肺结核患者的临床表现、CT扫描征象、手术方式、病理类型等进行回顾性分析。结果 以GGO为表现的早期肺癌并发肺结核以查体时发现多见(9/14),CT表现为陈旧性结核病灶并发混合密度GGO(mGGO) 12例;GGO与结核病灶位于同侧同叶4例。术前对患者进行规范抗结核药物治疗9例,术后继续行规范抗结核药物治疗6例。术前有3例患者行CT引导下肺穿刺活检确诊肺癌,其余11例为术中冰冻切片病理检查证实。行肺叶切除加纵隔淋巴结清扫10例,肺叶(GGO病灶所在处)切除加同侧异叶肺结核瘤局部切除2例,肺段切除1例,楔形切除1例。肺结核病灶标本经病理检查确诊10例,另4例依据病史及影像学表现符合陈旧性肺结核诊断;表现为GGO的早期肺癌病灶标本经病理检查确诊腺癌11例,鳞癌1例,腺鳞癌1例,大细胞癌1例。纵隔淋巴结病理检查均未见转移。本组患者术后均顺利康复,短期随访未见肿瘤复发、转移及结核复燃等。结论 GGO为表现的早期肺癌并发肺结核患者其临床表现无特异性,薄层CT扫描加动态观察有利于诊断。手术方式需在肺癌切除的基础上兼顾结核病灶的处理,规范的抗结核药物治疗加手术切除治疗效果满意。     

老年患者亚厘米肺结节术前CT随访分析

目的 对亚厘米肺结节进行CT随访,并观察其变化情况.方法 收集69例经病理证实为微浸润或浸润性腺癌的老年患者CT随访资料.结果 随访过程中,病灶增大者有32例,病灶内实性成分增多者有30例,其中有10例同时合并病灶增大及实性成分增多;2例磨玻璃灶中含空泡者病灶直径未见增大、但病灶内空泡被充填;另有5例病灶直径及性质均无变化.结论 亚厘米结节出现增大及实性成分增多提示恶性倾向.     

原发性结节肿块型肺黏液腺癌的CT表现与病理基础

目的分析原发性结节肿块型肺黏液腺癌的CT表现、随访变化，以提高对本病的认识。 方法分析80例经病理证实的原发性结节肿块型肺黏液腺癌患者的病理、临床及影像资料。患者均行胸部CT检查，其中57例患者行胸部CT平扫+增强检查，8例有间隔时间2周以上的随访CT。分析病灶影像学征象及动态CT随访变化。 结果微浸润肺黏液腺癌7例，浸润性肺黏液腺癌73例。单发病灶78例，多原发病灶2例。混杂磨玻璃结节20例，实性病灶60例。69例(86.2%)位于胸膜下，49例(61.2%)位于肺下叶。占比50%以上的征象有：类圆形46例、瘤肺界面清楚毛糙45例，分叶征70例、磨玻璃征43例。平扫病灶密度均低于肌肉，轻度强化19例，中度强化30例，明显强化8例，17例病灶内可见无强化的液性区域，血管造影征15例。CT动态随访变化多样，可短期保持稳定或迅速增长，或短期内实性成分减少而磨玻璃成分增多，或长期保持不变或缓慢增长。 结论原发性结节肿块型肺黏液腺癌好发于双肺下叶及胸膜下，多呈类圆形、瘤肺界面清楚毛糙，多伴有分叶征及磨玻璃征，以轻中度强化为主。CT动态随访变化多样。结合病灶的HRCT征象、CT增强及随访变化对诊断肺黏液腺癌有一定意义。     

老年肺腺癌pGGN浸润前与浸润性病变的CT特征及病理对照

目的探讨纯磨玻璃密度结节(p GGN)浸润前与浸润性病变老年肺腺癌的CT特征及病理分离的对应关系。方法筛选190例(共194个病灶)经手术病理证实为肺腺癌且最大径≤1 cm的p GGN老年患者的CT图像和病理资料。按IASLC/ATS/ERS国际多学科分类解读标准进行病理分类:非典型腺瘤样增生(AAH)38个、原位腺癌(AIS)62个、微浸润腺癌(MIA)38个、浸润性腺癌(IPA)56个;浸润前病变(AAH+AIS)100个,浸润性病变(MIA+IPA)94个。比较不同病理亚型的CT征象,主要包括:病变部位、病灶大小、病灶密度、支气管气像、血管改变、病灶边缘、瘤肺界面。ROC曲线分析浸润前病变与浸润性病变的最佳临界值。结果 AAH病变大小明显小于AIS、MIA、IPA(P<0.05);AAH血管改变率低于AIS、MIA、IPA(P<0.05);AAH癌肺界面清晰率明显低于AIS、MIA、IPA(P<0.05);不同病理分型间病变部位分布、病灶密度、支气管气像发生率、病变边缘情况差异均无统计学意义(P>0.05)。ROC曲线分析显示,浸润前病变及浸润性病变大小的临界值为0.83 cm,敏感度为82.81%,特异度为81.50%,ROC曲线下面积为0.89。结论最大径≤1 cm的p GGN老年肺腺癌中病变大小、血管改变、瘤肺界面可用于浸润前与浸润性病变的鉴别诊断,其中病变大小0.83 cm可作为浸润前与浸润性病变的临界值。     

Morphological observation of tumor infiltrating immunocytes in human rectal cancer

AIM: To investigate the morphological characterization of tumor infiltrating dendritic cells (TIDCs) and tumor infiltrating lymphocytes (TILs) in human rectal cancer. METHODS: Light and electron microscopy as well as im-munohistochemistry were used to observe the distributive and morphological changes of TIDCs and TILs. RESULTS: TIDCs were mainly located in tumor-surrounding tissue. The number of TIDCs in the earlier stage was higher than that in the later stage (P<0.01). TILs were mainly seen in adjacent tissue of cancers and tumor-surrounding tissue. There were more TILs in the earlier stage than that in the later stage (P<0.01). Under electron microscope, TIDCs were irregular in shape and exhibited many dendritic protrusions. It isn't obvious that cancer cells perforated the basement membrane and TILs were arranged along the basement membrane in the earlier stage. In the later stage, it is explicit that cancer cells perforated the basement membrane and surrounded by TILs. There were contacts among TIDCs, TILs and tumor cell. One TIDCs contacted one or several TILs which clustered around TIDCs. Glycogen granules were seen between TIDCs and TILs. CONCLUSION: The number of TIDCs and TILs is related with tumor progression There exist close relationships among TIDCs, TILs and tumor cell.     

Heparanase expression, degradation of basement membrane and low degree of infiltration by immunocytes correlate with invasion and progression of human gastric cancer

AIM： To disclose the mechanisms that accelerate or limit tumor invasion and metastasis in gastric cancer patients. METHODS： The heparanase expression, continuity of basement, degree of infiltration by dendritic cells and lymphocytes in gastric cancer tissues from 33 the early and late stage patients were examined by immunohistochemistry, in situ hybridization and transmission electron microscopy. RESULTS： Heparanase mRNA expression in the late stage patients with gastric cancer was stronger than that in the early stage gastric cancer patients. In the early stage gastric cancer tissues, basement membrane （BM） appeared intact, whereas in the late stage, discontinuous BM was often present. The density of Sl00 protein positive tumor infiltrating dendritic cells （TIDC） in the early stage gastric cancer tissues was higher than that in the late stage. The infiltrating degree of tumor infiltrating lymphocytes （TIL） in the early stage patients whose tumor tissues contained a high density of TIDC was significantly higher than that in the late stage gastric cancer tissues patients with a low density of TIDC. There were few cancer cells penetrated through the continuous BM of cancer nests in the early stage gastric cancers, but many cancer cells were found outside of the defective BM of cancer nests in the late stage. CONCLUSION： Our results suggest that strongheparanase expression is related with the degradation of BM which allows or accelerates tumor invasion and metastasis. However, high density of TIDC and degree of infiltration by TIL are associated with tumor progression in human gastric cancers.     

老年患者恶性胸水中肿瘤浸润免疫细胞体外活化

目的 观察老年患者恶性胸水中肿瘤浸润免疫细胞的活性.方法 分离恶性胸水单个核细胞(PEMCs),采用两步贴壁法,获得非贴壁细胞,树突细胞及淋巴细胞是其主要功能细胞成分.IL-2活化肿瘤浸润免疫细胞,SP法检测T淋巴细胞亚群的数量及免疫功能,SP法S-100蛋白染色检测树突细胞.结果 IL-2活化培养7 d后肿瘤浸润树突细胞(TIDC)和肿瘤浸润T淋巴细胞(TIL)数量明显增加(P<0.01).恶性胸水TIDC经过IL-2活化后具有抗原提呈功能.结论 IL-2活化肿瘤微环境中TIDC,使其恢复免疫监视功能,有效地负载肿瘤抗原,协同TIL等其他免疫细胞有效杀伤肿瘤细胞.     

Endoscopic ultrasound may be used to deliver gene expression signatures using digital mRNA detection methods to immunophenotype pancreatic ductal adenocarcinoma to facilitate personalized immunotherapy

Background & objectivesBiomarkers are increasingly required to molecularly characterize pancreatic ductal adenocarcinoma (PDAC) subgroup populations, to determine who may benefit from immune based targeted therapy. We evaluated the feasibility of gene expression signature detection and the respective landscape of specific tumor infiltrating lymphocytes (TILs), cancer/testis (CT) antigens, and immune checkpoints for possible future personalized immunotherapy eligibility.MethodsDedicated digital mRNA oncologic immune profiling of 770 genes using a Nanostring nCounter® PanCancer Immune Profiling Panel was performed using archived endoscopic ultrasound fine needle biopsy (EUS FNB) PDAC specimens as a case series in a tertiary care setting.ResultsThe spectrum of mRNA gene expression within the tumor specimens revealed that 44.8%, 10.0% and 50.7% of evaluated genes had a ≥ 2-fold increase, a ≤ 2-fold reduction or between <2 and >2 change of mRNA expression, when compared to normal controls. The corresponding landscape of TILs, CT antigens, and immune checkpoints highlighted several possibilities that could potentially be amenable to targeted personalized immunotherapy. This includes members of the Tumor Associated Macrophage family (CD68, CXCL5, and MARCO), members of the CT antigen family (PRAME, TTK and PBK) and the “second generation” checkpoints TIM3 and BTLA.ConclusionsOur study represents the ability to successfully perform digital mRNA expression profile analyses to immunophenotype PDAC EUS FNB specimens by evaluating the expression of >730 genes within the tumor immune microenvironment. This may facilitate the search for novel therapeutic targets, offering the opportunity to go beyond immune monotherapy, but perhaps to use combined immunomodulatory agents.     

胆囊腺癌中原癌基因C—erbB—2产物的表达及意义

本文应用抗原癌基因Ｃ－ｅｒｂＢ－２蛋白产物的抗体，检测３８例胆囊腺癌。结果发现，相当数量的胆管腺癌有Ｃ－ｅｒｂＢ－２过度表达，提示该肿瘤有Ｃ－ｅｒｂＢ－２基因的扩增。阳性产物定位于细胞膜。     

Survival impact of lymphocyte infiltration into the tumor of hepatocellular carcinoma in hepatitis B virus‐positive or non‐B non‐C patients who underwent curative resection

Aim

The prognostic value of lymphocyte infiltration into hepatocellular carcinoma (HCC) is still controversial, and it has not been reported in hepatitis B virus (HBV)‐positive or non‐B non‐C (NBNC) HCC. The aim of this study is to assess the prognostic significance of lymphocyte infiltrate in tumor for HBV‐positive and NBNC HCC patients.

Methods

This study investigated 145 HBV‐positive or NBNC patients who underwent hepatectomy for HCC between January 2001 and May 2009. Cumulative recurrence rate, overall survival (OS), and clinicopathological parameters were analyzed according to lymphocyte infiltration in tumor.

Results

In patients with low lymphocyte infiltration, the 5‐year recurrence rate was higher and OS was poor (86.4 and 44.1%, respectively) than that of the patients with high lymphocyte infiltration (55.3 and 83.7%, respectively). Multivariate analyses revealed that independent risk factors for recurrence were low albumin value (hazard ratio [HR] 2.33, P = 0.009), high American Joint Committee on Cancer (AJCC) T stage (HR 2.31, P < 0.0001), high α‐fetoprotein (AFP) value (HR 2.06, P = 0.005), and low lymphocyte infiltration (HR 2.50, P = 0.0001). The independent risk factors for OS were low albumin value (HR 3.69, P = 0.003), high AJCC T stage (HR 2.10, P = 0.049), high AFP value (HR 3.98, P < 0.001), and low lymphocyte infiltration (HR 3.47, P = 0.001).

Conclusions

Lymphocyte infiltrate in tumor is significantly associated high recurrence rate and poor overall survival. Evaluation of the infiltrating lymphocyte could improve the prediction of prognosis in HCC patients after curative resection.     

Clinicopathological study of colorectal mucinous carcinoma in Taiwan: A multivariate analysis

The clinicopathological significance of colorectal mucinous carcinoma is controversial, although some authors feel mucinous carcinoma has a worse prognosis than that of non-mucinous carcinoma. To clarify the significance of this type of carcinoma in Taiwan, a retrospective review of patients with colorectal carcinoma treated at Chang Gung Memorial Hospital between 1984 and 1988 was undertaken. During this period, 53 mucinous carcinomas and 401 non-mucinous carcinomas fulfilling the inclusion criteria were analysed. Mucinous carcinomas were more common in patients 39 years of age or under (P < 0.005). Most mucinous carcinomas were located in the rectum/rectosigmoid, followed by the right colon; however, the right colon had a higher relative incidence (38 vs 8%, respectively; P < 0.005). Mucinous carcinomas presented at a significantly more advanced stage (23 vs 8%, respectively, stage D disease; P < 0.005) and had a markedly lower curative resection rate (68 vs 84%, respectively; P < 0.05). Following curative resection, mucinous carcinomas tended to have an increased incidence of subsequent distant metastasis (27.8 vs 18.8%, respectively; P < 0.005). The overall survival rate of patients with mucinous carcinoma was worse than that of non-mucinous carcinoma (P < 0.005). Multivariate analysis showed that clinically important predictive factors were stage of disease on diagnosis and subsequent distant metastasis. The mucinous histological type itself was not an independent prognostic factor in colorectal cancer.     

肿瘤浸润淋巴细胞治疗老年人恶性胸水的疗效分析

目的探讨肿瘤浸润淋巴细胞（ＴＩＬ）治疗老年癌症患者恶性胸水的有效率。方法应用癌症患者自体胸水的ＴＩＬ培养、扩增后产物经胸腔内输注治疗２１例老年人恶性胸水,每隔日１次,至少４次。结果２１例经治疗后,胸水中淋巴细胞增加,肿瘤细胞逐渐减少,胸腔积液逐渐吸收,１个月后１９例达完全缓解和部分缓解,有效率为９０．５％。结论自体胸水ＴＩＬ可治疗恶性胸水,同时可提高老年癌症患者的免疫功能,对机体无毒副作用。