腹腔镜辅助再次手术治疗先天性巨结肠及巨结肠同源病的临床分析

目的 探讨腹腔镜辅助再次手术治疗先天性巨结肠（HD）或巨结肠同源病（HAD）的临床价值.方法 选择2010年6月至2013年6月于华中科技大学同济医院附属同济医院经手术治疗及保守治疗无效的30例HD或HAD患儿为研究对象,对其进行腹腔镜辅助再次手术治疗.本研究遵循的程序符合华中科技大学同济医学院附属同济医院人体试验委员会所制定的伦理学标准,得到该委员会批准,征得受试对象监护人的知情同意,并与之签署临床研究知情同意书.结果 本研究30例患儿再次手术均成功完成（100.0％）,其中,腹腔镜辅助再次手术成功为27例（90.0％）,因腹腔肠管粘连严重而行中转开腹治疗成功患儿为3例（10.0％）.30例患儿随访结果显示,术后无任何异常症状患儿为16例（53.3％）,术后出现污粪、便秘症状患儿为14例（46.7％,经保守治疗症状缓解）.结论 对经手术和保守治疗无效的HD或HAD患儿进行腹腔镜辅助再次手术具有手术创伤小、术后恢复快、手术效果确切、短期随访疗效满意等优势,但对该类患儿再次手术术式的选择,仍需要综合考虑患儿病情及首次根治术术式,采取个体化治疗方案,以达到最佳治疗效果.     

NDRG1 as a biomarker for metastasis,recurrence and of poor prognosis in hepatocellular carcinoma

N-myc downstream-regulated gene 1 (NDRG1) has been reported to be a multifunctional protein associated with carcinogenesis, however, the cellular function of NDRG1 remains elusive in human cancers. Here, our proteomics profile analysis of HCC tissues with different metastatic capabilities revealed that NDRG1 was correlated with metastasis and recurrence in HCC patients after liver transplantation (LT). Immunohistochemical staining of 143 HCC patients after LT showed that NDRG1-positive expression had poor prognosis, either for shorter disease-free survival or overall survival (P < 0.001), compared with NDRG1-negative expression. Multivariate analysis confirmed NDRG1 as an independent prognostic value (P < 0.001). In addition, in vitro experiments HCC cells with small interfering RNA against NDRG1 significantly suppressed its proliferation, colony formation, invasion and migration ability. Microarray analysis revealed that NDRG1 modulated the expression of genes associated with transmembrane transporter activity, chemoattractant activity, immune response, cell adhesion and cell proliferation process. Taken together, these results suggested that NDRG1 was an important molecule in controlling HCC metastasis and thus suggested as a novel biomarker for predicting HCC recurrence after LT.     

Molecular Mechanisms of Tyrosine Kinase Inhibitor Resistance Induced by Membranous/Cytoplasmic/Nuclear Translocation of Epidermal Growth Factor Receptor

IntroductionThe molecular mechanism underlying the induction of resistance to tyrosine kinase inhibitors (TKIs) via the membranous/cytoplasmic/nuclear translocation of EGFR has not yet been reported.MethodsWe performed immunohistochemistry to detect the distribution of EGFR in lung adenocarcinoma specimens after TKI treatment and analyzed the relationship between different EGFR locations and patient survival duration. Mass spectrometry analysis and immunoprecipitation were performed to show the interaction of cytosolic EGFR with YY1 associated protein 1 (YAP) and salt inducible kinase 2 (SIK2). Dual-luciferase assays, immunoblotting, real-time polymerase chain reaction, and functional experiments were used to elucidate the role of EGFR cytoplasmic/nuclear translocation in Hippo pathway dysregulation.ResultsPatients with advanced lung adenocarcinoma with membranous mutant EGFR (19del or 21 L858R) showed significantly longer progression-free survival than those with cytoplasmic mutant EGFR after gefitinib treatment. The concentration that inhibits 50% in PC-9 with cytoplasmic EGFR was higher than that in hunman non-small cell lung cancer 827 with membranous EGFR. During first-generation TKI resistance induction, membrane EGFR translocated to the cytoplasm/nucleus, accompanied by the Hippo pathway inhibition. Cytoplasmic EGFR and SIK2 interaction inhibited large tumor suppressor kinase 1 (LATS1) and macrophage stimulating 1 (MST1) interaction, promoting YAP nuclear translocation. However, cells with osimertinib-induced resistance also showed EGFR translocation and lower phospho-EGF receptor but did not show Hippo pathway inhibition. Moreover, osimertinib and erlotinib could restore sensitivity to each other in resistant cells.ConclusionsPlasma/nuclear translocation of EGFR and inhibition of the Hippo pathway are some of the important mechanisms underlying the resistance induced by first-generation TKIs. Membrane/plasma translocation of EGFR induced by osimertinib may be another resistance phenomenon besides MNNG HOS transforming gene (c-MET) amplification, C797S mutation, and ERK pathway inhibition.     

植骨加钢板内固定治疗胫骨平台骨折56例

目的探讨常规植骨加支撑钢板治疗胫骨平台塌陷骨折的临床效果。方法回顾2000年1月一2004年12月收治的胫骨平台骨折72例,按Schatzker分型II型14例,III型19例,IV型9例,V型10例,VI型4例。男48例,女24例,年龄在19一61岁,平均42岁,闭合性损伤68例,开放性损伤4例。72例均根据骨折情况灵活选取切口行切开复位支撑钢板内固定。关节面塌陷56例行自体骨或同种异体骨植骨支撑,术后早期应用CPM机活动膝关节。结果56例全部获得随访,随访8一60个月,平均33个月。56例全部获得骨折愈合,膝关节功能按Merchant标准综合分析,优32例,良16例,可6例,差2例,优良率为85.71%。结论灵活选取切口应用常规植骨加支撑钢板内固定治疗胫骨平台骨折,固定牢靠,可早期功能锻炼,关节功能恢复好,并发症少,后期无一例塌陷畸形。     

Diagnostic value of the preoperatively detected radiological transition zone in Hirschsprung’s disease

Background and objective

The cardinal diagnostic sign of congenital aganglionic megacolon, or Hirschsprung’s disease (HD), is an aganglionic segment of the distal colon or rectum. To determine the surgical planning of a radiological transition zone (TZ) in HD, this study investigated the association between a radiological TZ and the bowel resection length.

Methods

A prospective observational study was conducted in children (n?=?192) with suspected HD determined by radiological TZ on contrast barium enema, and who underwent pull-through operations. The bowel resection length was ≥10 cm above the proximal radiological TZ levels and confirmed by intraoperative frozen sections. In the contrast enema, the presence and level of a radiological TZ were recorded. Correlation of the TZ features with ganglion cells assessed by immunostaining of neuronal nuclei (NeuN) and the odds ratio were calculated.

Results

The sensitivity and specificity for diagnosing HD by the presence of a radiological TZ were 86.9 and 92.1%, respectively; Youden’s index was 79.0%. The positive and negative predictive values were 91.7 and 87.6%. The kappa value indicating an association between TZ and HD was 0.776 (P?<?0.05). The correlation rate between a radiological TZ and the pathological results was 88.5% in the rectosigmoid colon and 44.4% in the descending colon, and was higher in children older than 3 months (85.3%) than in infants (69.0%).

Conclusion

A preoperatively determined radiological TZ has potential value to identify the length of resected bowel in patients with HD, and it also has a high predictive value for diagnosis of HD.

     

SPOC联合TBL教学模式在中西医结合本科生外科手术学教学中的应用

探讨SPOC联合TBL教学模式在中西医结合本科生外科手术学教学中的应用效果,以有效提高学生的理论成绩和临床技能成绩,提高学生的综合能力及团队协作能力,提高学生教学满意度。     

SCHIP1促进Hippo通路的激活抑制结肠癌的发生发展

目的:检测SCHIP1在结肠癌的组织和细胞中的表达水平以及其在结肠癌中对Hippo通路的影响。方法:利用TCGA数据库分析SCHIP1在结肠癌中的表达情况;免疫组化的方法检测SCHIP1在结肠癌组织标本中的表达情况;采用Transwell试验、集落实验及MTS检测对细胞迁移和增殖能力进行检测;采用Western blot检测YAP、P-YAP、CTGF在结肠癌中的表达情况。结果:TCGA数据库显示结肠腺癌中SCHIP1的表达低于正常组织;SCHIP1在结肠癌组织及细胞系中表达较低;SCHIP1过表达抑制了RKO细胞迁移和增殖能力;SCHIP1低表达促进了RKO细胞的迁移和增殖;过表达SCHIP1的RKO细胞明显抑制了YAP、CTGF的表达,促进了P-YAP的表达。低表达SCHIP1的RKO细胞促进了YAP、CTGF的表达,抑制了P-YAP的表达。结论:SCHIP1增强了结肠癌中Hippo通路活性,抑制结肠癌的发生进展;SCHIP1可能作为结肠癌治疗的一个潜在靶向分子。     

干细胞标记物CK19、Notch3、CD133、P75NTR、STRO-1及ABCG2在肺鳞癌中的表达及意义

背景与目的 已有研究表明在肿瘤中存在着能够自我更新与多向分化的肿瘤干细胞,它们与正常人体内的干细胞有着相似的特征.本研究选取了被认为可作为干细胞标记物的部分抗体,以观察它们在肺鳞癌中的表达及意义.方法 采用S-P免疫组织化学方法,对54例手术切除肺鳞癌标本进行了CK19、Notch3、CD133、P75NTR、STRO-1及ABCG2的检测,另外选取了10例正常肺组织标本进行对照.结果 54例肺鳞癌标本中,除发现STRO-1及P75NTR在所有病例均为阴性表达外,其余标记均存在不同程度的阳性表达,但是阳性细胞的分布无规律性.其中,CK19阳性率为66.67%(36/54),Notch3为87.04%(47/54),CD133为50%(27/54),ABCG2为61.11%(33/54),并且Notch3、CD133和ABCG2在中低分化肺鳞癌中的表达高于高分化鳞癌(P＜0.05),而CK19、CD133和ABCG2在有淋巴结转移的肺鳞癌中的表达高于无淋巴结转移(P＜0.05),在连续切片中4种标记同时阳性的细胞数均少于总细胞数目的2%,3种及4种抗体共同阳性细胞所占百分比与鳞癌的分化程度和是否有淋巴结转移无统计学相关.结论 肺鳞癌中存在着某些干细胞标记物的表达,其表达程度与肺鳞癌的分化程度及淋巴结转移相关,但是阳性细胞在组织学的分布上无规律性,同时表达多种干细胞标记的肿瘤细胞数少于2%,可能为肿瘤干细胞.     

肾动脉变异评价与肾移植变异动脉吻合术式研究进展

因为肾动脉变异,其来源、数目较复杂,肾移植疗效恢复很大程度依靠对动脉精准吻合、即时恢复血液循 环,本综述旨在通过充分认识及评价肾动脉变异,在肾移植术中对变异动脉选择最佳的血管吻合术式,以达到移 植肾及时恢复功能,防止并发症发生。     

新生儿含肝组织的巨型脐膨出的临床治疗抉择探讨

目的:回顾分析含有肝脏组织的巨型脐膨出(GO)的临床特征,探讨最佳治疗方式,改善预后,提高GO患儿救治率。方法:收集2009年1月至2019年5月在武汉儿童医院新生儿外科住院的GO患儿,治疗方法包括：1.使用类似Silo袋的方法,分期手术;2.一期直接或联合补片修补;3.保守治疗2～8周后延期一期手术。收集的数据包括患...