乳腺癌新辅助化疗后残留癌组织的病理分析

目的：探讨和分析乳腺癌新辅助化疗后残留癌组织变性区病理形态特点，为正确评价该治疗方法提供理论依据。方法：应用病理形态学、免疫组化技术以及细胞凋亡检测技术（ＰＣＤ）进行分析。结果：１０例导管浸润癌中有２例未找到残留癌组织，１例仅见少量残留癌组织，７例有不同程度癌组织残留。残留癌组织分为变性癌组织区（ＤＣＣ）和非变性癌组织区（ＮＤＣＣ）。比较两者癌细胞的ＰＣＮＡ表达，ＮＤＣＣ明显高于ＤＣＣ，而ＰＣＤ检     

乳腺癌新辅助化疗后的形态学改变与鉴别诊断

目的总结新辅助化疗后乳腺癌组织、癌旁乳腺组织及淋巴结的形态学改变,并提出相关鉴别诊断注意点。方法收集入组新辅助化疗病例119例,治疗前均行核芯针穿刺活检（CNB）。复习新辅助化疗后手术切除标本的病理切片,分别记录癌组织、癌旁乳腺组织及淋巴结的治疗后改变,并根据上述改变提出鉴别诊断的注意点。结果癌组织可出现不同程度的退变及间质纤维化等多种反应,癌细胞的空泡变性、合体癌细胞等需与泡沫细胞、多核巨细胞等鉴别,免疫组化染色（AE1/AE3、CD68等）有助益。癌组织的间质反应可作为新辅助化疗后肿瘤完全消失的组织学线索。淋巴结存在与原发灶相似的治疗后改变,但出现比例较低。癌旁乳腺组织可出现导管上皮增生等改变,需与残存的导管内癌鉴别。结论乳腺癌新辅助化疗后的形态学改变会造成诊断困难,复习治疗前CNB切片、充分及必要的取材、免疫组化染色（AE1/AE3、CD68等）有助于诊断及疗效评价。     

新辅助化疗对乳腺癌COX-2、Ki-67表达和微血管密度的影响

目的:探讨在乳腺癌新辅助化疗中COX-2、Ki-67表达和微血管密度(MVD)的变化及其意义.方法:应用免疫组织化学法检测48例乳腺癌新辅助化疗前后标本中COX-2、Ki-67的表达和MVD.结果:新辅助化疗前后乳腺癌组织中COX-2、Ki-67表达和MVD变化显著,分别由化疗前的62.5%,(46.81±23.17)%和(32.21±7.80)%.降到化疗后的41.7%、(33.23±18.11)%和(28.77±10.01)%,P<0.05.化疗前后COX-2阳性的乳腺癌组织中Ki-67、MVD均显著高于COX-2阴性组.P<0.05.结论:新辅助化疗通过抑制COX-2的表达,降低肿瘤细胞增殖活性,减少肿瘤新生血管生成,降低乳腺癌细胞的浸润转移能力.     

乳腺癌基质金属蛋白酶-9及前哨淋巴结CKl9 mRNA表达的相关性

目的研究乳腺癌组织中基质金属蛋白酶(matrix metallo-proteinases-9,MMP-9)基因表达与乳腺癌前哨淋巴结(SLN)微转移分子CK19 mRNA检测的关系,揭示乳腺癌的浸润和转移机制.方法应用S-P免疫组化法检测76例乳腺浸润癌组织和20例乳腺非恶性肿瘤组织中MMP-9的表达情况采用原位杂交技术检测同组76例乳腺浸润癌SLN微转移分子CK19 mRNA的表达,同时与常规病检法比较其检测敏感性,并比较淋巴结转移组、微转移组、无转移组患者的临床资料.结果76例乳腺浸润癌中,常规病检无淋巴结转移36例,淋巴结转移40例.MMP-9在淋巴结转移组和无淋巴结转移组原发灶阳性表达的平均秩次为45.95、30.19,转移组明显高于无转移组.两者差异具有显著性(P＜0.05).原位杂交法检出36例阴性淋巴结中9例有CK19 mRNA表达.原位杂交法与常规病检法转移的检出率比较差异有统计学意义(P＜0.05).结论淋巴结的转移与MMP-9的表达具有相关性.检测MMP-9蛋白表达将有助于判断乳腺癌的转移及预后.应用原位杂交法可明显提高乳腺癌的检出率.     

淋巴化疗与静脉化疗对胃癌淋巴转移灶细胞凋亡的影响

目的探讨淋巴化疗与静脉化疗对胃癌淋巴转移灶细胞凋亡的影响。方法我院2006年6月至2009年3月行胃癌根治性切除术的患者30例,术后经病理证实为转移癌,其中15例在术中进行淋巴化疗,15例进行静脉化疗,采用免疫组化ABC法检测两组不同化疗方式的胃癌患者原发灶淋巴转移灶P53、Bcl-2及CD95基因的表达,并用原位末端脱氧核苷转移酶标记法(TUNEL)检测细胞凋亡情况。结果术中淋巴化疗可以有效抑制Bcl-2的表达,明显增强胃癌淋巴结转移灶癌细胞P53和CD95的表达,并与细胞凋亡呈正相关;静脉化疗未见明显Bcl-2的表达抑制、胃癌淋巴结转移灶癌细胞P53和CD95的表达增强;两组相比差异具有统计学意义(P<0.05)。结论淋巴化疗可影响P53、Bcl-2及CD95基因的表达,进而加速淋巴系统肿瘤细胞凋亡,对淋巴结转移灶具有直接治疗作用,值得临床推广。     

新辅助化疗后食管癌病理形态学改变

目的总结新辅助化疗后食管癌组织、癌旁食管组织及周围淋巴结的形态学改变,并提出相关鉴别诊断要点。方法收集新辅助化疗病例85例,治疗前均行胃镜活检,病理诊断明确。回顾分析新辅助化疗后切除标本的组织形态,观察癌组织、癌旁食管组织及周围淋巴结在治疗后的改变。结果肿瘤组织大体形态和肿瘤细胞形态发生较多改变。肿瘤组织出现不同程度的退变及间质纤维化等改变,肿瘤细胞出现分化更差的形态改变。淋巴结萎缩,转移灶可发生与原发灶相似的治疗后改变。癌旁鳞状上皮组织表现为棘层肥厚、棘层松解,气球样变和角质囊肿形成。退变的肿瘤细胞、合体癌细胞等需与泡沫组织细胞、多核巨细胞等鉴别。免疫组化染色(AE1/AE3、MNF-116、CD68等)有助于诊断。结论食管癌新辅助化疗后的形态学改变会造成诊断困难,回顾治疗前胃镜病理切片、充分取材及免疫组化染色有助于诊断与疗效评价。     

新辅助化疗后乳腺癌腋下淋巴结的超声影像分析

目的分析常规超声检查在新辅助化疗后乳腺癌腋下淋巴结评估中的作用。方法对2013年3月至2014年3月在复旦大学附属肿瘤医院新辅助化疗后的254例乳腺癌患者腋下淋巴结行常规超声、磁共振成像及钼靶X线检查并与手术病理检查结果进行对照分析。结果病理检查显示254例新辅助化疗后乳腺癌患者腋下淋巴结转移161例(63.4%,161/254),无淋巴结转移93例(36.6%,93/254)。与病理检查结果对照,术前常规超声正确诊断159例(62.6%,159/254),其中正确诊断腋下淋巴结转移93例,无淋巴结转移66例。MRI正确诊断118例(46.5%,118/254),其中正确诊断腋下淋巴结转移50例,无淋巴结转移68例。钼靶X线正确诊断134例(52.8%,134/254),其中正确诊断腋下淋巴结转移60例,无淋巴结转移74例。254例新辅助化疗后常规超声、MRI和钼靶X线扫查诊断乳腺癌患者腋下淋巴结转移的正确率分别为62.6%、46.5%、52.8%,敏感度分别为57.8%、31.1%、37.3%。常规超声扫查正确诊断新辅助化疗后乳腺癌患者腋下淋巴结转移的正确率和敏感度均高于MRI和钼靶X线检查。结论术前常规超声检查对新辅助化疗后乳腺癌患者腋下淋巴结转移状态的评估有一定的临床诊断价值。     

食管鳞状细胞癌组织中淋巴管密度的检测及其临床意义

目的 探讨食管鳞状细胞癌组织中淋巴管形成的临床病理意义.方法 应用单克隆抗体D2-40检测食管癌周围和中心区以及正常食管组织中淋巴管密度(LVD),分析其与食管癌分化程度、浸润深度、淋巴管侵犯和淋巴结转移的关系.结果 肿瘤周围区LVD明显高于中心区和正常组织(P＜0.01).肿瘤周围区LVD与淋巴管侵犯和淋巴结转移密切相关(P＜0.01),而与肿瘤的分化程度和浸润深度无关(P＞0.05);肿瘤中心区LVD与肿瘤分化程度、浸润深度、淋巴管侵犯和淋巴结转移均无相关性(P＞0.05).结论 食管癌主要是肿瘤周围区存在着淋巴管形成,检测肿瘤周围淋巴管密度可以预测肿瘤淋巴结转移.     

ⅠB2期子宫颈鳞癌患者新辅助化疗后淋巴结转移情况临床分析

目的探讨新辅助化疗后ⅠB2期子宫颈鳞癌淋巴结转移的情况。方法回顾性分析179例新辅助化疗的ⅠB2期宫颈鳞癌患者的病例资料,根据病理结果记录计算淋巴结转移情况。分析淋巴结转移与临床病理特征的关系。结果有淋巴结转移40例(22.3%)。新辅助化疗后的ⅠB2期子宫颈鳞癌淋巴结转移与患者年龄(40岁)(P<0.005)、分化程度高低(P<0.010)、深肌层浸润(P<0.005)、是否脉管浸润(P<0.005)有关。结论新辅助化疗可降低宫颈癌患者的淋巴结转移率。新辅助化疗后的ⅠB2期子宫颈鳞癌淋巴结转移与患者年龄、分化程度、浸润深度、脉管浸润有关。     

乳腺癌基质金属蛋白酶-9及前哨淋巴结CK19mRNA表达的相关性

目的：研究乳腺癌组织中基质金属蛋白酶（matrixmetallo-proteinases-9，MMP-9）基因表达与乳腺癌前哨淋巴结（SLN）微转移分子CKl9mRNA检测的关系，揭示乳腺癌的浸润和转移机制。方法：应用S—P免疫组化法检测76例乳腺浸润癌组织和20例乳腺非恶性肿瘤组织中MMP-9的表达情况；采用原位杂交技术检测同组76例乳腺浸润癌SLN微转移分子CK19mRNA的表达，同时与常规病检法比较其检测敏感性，并比较淋巴结转移组、微转移组、无转移组患者的临床资料。结果：76例乳腺浸润癌中，常规病检无淋巴结转移36例，淋巴结转移40例。MMP-9在淋巴结转移组和无淋巴结转移组原发灶阳性表达的平均秩次为45．95、30．19，转移组明显高于无转移组，两者差异具有显著性（P〈0．05）。原位杂交法检出36例阴性淋巴结中9例有CK19mRNA表达，原位杂交法与常规病检法转移的检出率比较差异有统计学意义（P〈0．05）。结论：淋巴结的转移与MMP-9的表达具有相关性，检测MMP-9蛋白表达将有助于判断乳腺癌的转移及预后。应用原位杂交法可明显提高乳腺癌的检出率。     

乳腺癌前哨淋巴结活检在新辅助化疗后的应用价值

目的通过对比术前未接受化疗和术前接受新辅助化疗两组乳腺癌患者前哨淋巴结活检的结果,探讨对术前接受新辅助化疗后降期的患者以核素法行前哨淋巴结活检的临床价值。方法以本院2006年4月~2009年3月期间收治的99例乳腺癌患者作为研究对象。术前未行化疗组60例,临床分期为T1~2N0M0,直接行前哨淋巴结活检。术前新辅助化疗组39例,临床分期T2~3N0M0,患者术前先给予3~4个疗程的新辅助化疗,降期为T1~2N0M0后再行前哨淋巴结活检。所有患者术前均经乳晕下4点平均注射99m锝标记的非过滤硫胶体,术中用γ探针探测腋窝具有放射活性的前哨淋巴结并切除,然后常规清扫腋窝Ⅰ、Ⅱ组淋巴结。术后对前哨淋巴结活检和腋窝淋巴结清扫的病理结果进行比较分析。结果A组成功率、假阴性率、灵敏度、特异度、准确性、阳性预测值和阴性预测值分别为98.3%、3.3%、96.7%、100%、98.3%、100%和96.7%。B组分别为100%、10%、90%、100%、94.9%、100%和90.5%。两组比较假阴性率、准确性均无统计学差异。(P均>0.05)。结论对新辅助化疗后降期的局部进展期乳腺癌患者,以核素法行前哨淋巴结活检仍能够获得较高的成功率,同早期乳腺癌患者相比假阴性率没有统计学差异。     

乳腺癌48例新辅助化疗前后超声声像图的变化

目的 探讨超声对乳腺癌新辅助化疗疗效评价的意义.方法 48例进行新辅助化疗的乳腺癌患者,均于化疗前、化疗后对乳腺癌原发灶进行声像图的观察及分析.结果 48例患者新辅助化疗后超声检查显示,化疗前后原发灶明显缩小甚至消失,原发灶内血流丰富程度降低或消失;最高流速(Vmax),和阻力指数(RI)降低(P ＜0.01,P＜ 0.01) ;相应病例腋窝淋巴结转移灶也呈现上述表现.结论 利用对乳腺病灶化疗前后的超声检查,可为新辅助化疗提供有效、安全的疗效观察手段.     

Application of neoadjuvant chemotherapy combined with anlotinib in occult breast cancer: A case report and review of literature

BACKGROUNDOccult breast cancer (OBC) is a special type of breast cancer presenting as axillary lymph node metastasis with undetectable primary lesions in the breast. Due to its low incidence and unique clinical manifestations, there is a lack of consensus on the diagnosis and treatment of OBC. We report a case of OBC treated with neoadjuvant chemotherapy combined with anlotinib. The treatment was well tolerated, and the patient achieved a pathologic complete response.CASE SUMMARYA 53-year-old woman presented with a lump in her right axillary area with no primary lesions in the breast. Pathological biopsy confirmed right axillary metastatic carcinoma. Immunohistochemical staining results were positive for progesterone receptor, cytokeratin 7, specific breast markers GATA3 and gross cystic disease fluid protein-15. Tumor cells were negative for estrogen receptor, human epidermal growth factor receptor-2, cytokeratin 5/6, cytokeratin 20, and villin. The patient was diagnosed with OBC, and she underwent neoadjuvant chemotherapy combined with anlotinib. Mastectomy plus axillary lymph node dissection was performed. The patient achieved pathologic complete response with no residual invasive tumor cells in the breast or axillary lymph nodes. Postoperatively, she received adjuvant radiotherapy and endocrine therapy.CONCLUSIONNeoadjuvant chemotherapy and anlotinib had good efficacy and safety in the treatment of OBC and may be a new therapeutic option.     

Imaging Biomarkers for Precision Medicine in Locally Advanced Breast Cancer

Guidelines from the American National Comprehensive Cancer Network recommend neoadjuvant chemotherapy to patients with locally advanced breast cancer (LABC) to downstage tumours before surgery. However, only a small fraction (15%–17%) of LABC patients achieve pathological complete response (pCR); that is, no residual tumour in the breast, after treatment. Measuring tumour response during neoadjuvant chemotherapy can potentially help physicians adapt treatment, thus potentially improving the pCR rate. Recently, imaging biomarkers that are used to measure the tumour's functional and biological features have been studied as pretreatment markers for pCR or as an indicator for intratreatment tumour response. Also, imaging biomarkers have been the focus of intense research to characterise tumour heterogeneity as well as to advance our understanding of the principle mechanisms behind chemoresistance. Advances in investigational radiology are moving rapidly to high-resolution imaging, capturing metabolic data, and performing tissue characterisation and statistical modelling of imaging biomarkers, with an end point of personalised medicine in breast cancer treatment. In this commentary, we present studies within the framework of imaging biomarkers used to measure breast tumour response to chemotherapy. Current studies are showing that significant progress has been made in the accuracy of measuring tumour response either before or during chemotherapy, yet the challenges at the forefront of these works include translational gaps such as needing large-scale clinical trials for validation and standardisation of imaging methods. However, the ongoing research is showing that imaging biomarkers may play an important role in personalised treatments for LABC.     

纳米碳混悬液作图法在乳腺癌新辅助化疗后腋窝淋巴结清扫中检出数目及腋窝微小淋巴结检出数目中的临床优势

目的对比纳米碳混悬液作图法与无染料法在乳腺癌新辅助化疗后腋窝淋巴结清扫中淋巴结检出数目及腋窝微小淋巴结检出数目中的效果。方法选择四川省肿瘤医院乳腺外科2018年1月1日至2018年7月1日经新辅助治疗后拟接受腋窝淋巴结清扫手术的乳腺癌患者66例,行前瞻性研究。采用随机数字表法随机分为纳米碳作图法组(33例)和对照组(33例),分别使用术前24 h皮下注射纳米碳后再行腋窝淋巴结清扫与不使用染料直接行腋窝淋巴结清扫两种方法,统计两组患者腋窝淋巴结检出数目及腋窝微小淋巴结检出数目情况。结果纳米碳作图法组腋窝淋巴结检出数目及微小淋巴结检出数目均高于对照组,差异均有统计学意义[腋窝淋巴结数目:(19.3±6.2)枚与(14.9±6.7)枚,P=0.007;腋窝微小淋巴结数目:2.0(0.5,3.0)枚与0(0,1.0)枚,Z=-4.328,P<0.001]。结论纳米碳混悬液作图法可以增加乳腺癌新辅助化疗后腋窝淋巴结清扫中淋巴结检出数目,同时对一些不易发现的腋窝微小淋巴结的检出也具有优势。     

Plasma transforming growth factor beta1 in breast cancer patients treated with CMF chemotherapy

BACKGROUND: In early breast cancer patients the transformed epithelial cells are thought to be sensitive to transforming growth factor beta1 (TGFbeta1)-mediated growth arrest. TGFbeta1 may therefore act as an anti-tumour promoter. However, in advanced breast cancer resistance to such TGFbeta1 action develops. Neoplastic cells produce TGFbeta1, which may enhance tumour invasion and metastasis, mainly by intensifying angiogenesis, which is an immunosuppressive action. In the light of the potential role of TGFbeta1 in breast cancer pathogenesis, an understanding of the effect of applied therapeutic methods on plasma TGFbeta1 concentration is essential. OBJECTIVE: To investigate the effect of adjuvant chemotherapy on plasma transforming growth factor beta1 (TGFbeta1) concentration in breast cancer patients with metastases to axillary lymph nodes. METHOD: Fifteen stage II breast cancer patients on adjuvant chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were studied along with 15 healthy premenopausal women. RESULTS: Plasma TGFbeta1 concentration (determined by the ELISA method) in the breast cancer patients did not differ significantly from that of the healthy women. Adjuvant CMF chemotherapy significantly decreased plasma TGFbeta1 concentration in those pre-menopausal breast cancer women with metastases to axillary lymph nodes. CONCLUSION: The possible pathogenic action of this growth factor in stage II breast cancer disease warrants further investigation to elucidate whether the induced decrease of blood TGFbeta1 concentration is essential to successful chemotherapy.     

Reduced lymph node harvest after neoadjuvant chemotherapy in gastric cancer

This retrospective study investigated the impact of neoadjuvant chemotherapy on the number of lymph nodes harvested in patients with T(3)/T(4) gastric cancer. Lymph node counts in 58 patients who received preoperative neoadjuvant chemotherapy were compared with those in 168 patients who received surgery alone. Significantly more patients (n = 14, 24.1%) treated with neoadjuvant chemotherapy had < 15 lymph nodes harvested compared with patients (n = 13, 7.7%) treated with surgery alone. A significant correlation between the total number of harvested lymph nodes and the number of metastatic lymph nodes (mLNs) existed in both groups. Neoadjuvant chemotherapy was the only factor associated with the retrieval of < 15 lymph nodes. The number of mLNs was an independent predictive factor for overall survival. Although neoadjuvant chemotherapy decreased the number of lymph nodes harvested, the number of mLNs may still be an acceptable prognostic factor in patients with gastric cancer, following neoadjuvant chemotherapy.     

乳腺癌新辅助化疗对前哨淋巴结活检的影响

随着近年来新辅助化疗在乳腺癌治疗领域中的应用,其在增加保乳率及肿瘤降期方面有着明显优势。乳腺癌新辅助化疗后,对前哨淋巴结的评估影响患者的后续治疗及预后,但是新辅助化疗前患者腋窝淋巴结临床状态影响患者最终治疗决策,且仍存在争议。本文对近年来国内外关于新辅助化疗后前哨淋巴结活检方面的研究进展做一综述。     

超声造影诊断乳腺癌的研究进展

CEUS作为一种血池造影成像,在临床的应用逐渐增多,在乳腺癌的诊断及疗效评价等方面也有一定临床价值。本文就CEUS对乳腺癌的诊断、转移淋巴结的显示、新辅助化疗疗效评价及乳腺癌术后瘢痕与复发鉴别等的研究进展进行综述。     

Detectability of Hygroscopic Clips Used in Breast Cancer Surgery

Sonographically detectable clips were introduced over the last decade. We retrospectively studied the rate and duration of sonographically detectable clip detectability in patients with breast cancer who had sonographically detectable clips inserted over a 2‐year period. Nine of 26 patients had neoadjuvant chemotherapy, with all clips remaining detectable 140 to 187 days after insertion. Six of the 9 had intraoperative sonographic localization, with 1 reoperation (17%). Eleven additional patients with nonpalpable tumors and sonographically detectable clips had intraoperative sonographic localization with 1 reoperation (9%). In 1 patient, a sonographically detectable clip enabled intraoperative identification of a suspicious lymph node. There were no complications or clip migration. Sonographically detectable clips are helpful in breast cancer surgery with and without neoadjuvant chemotherapy, remaining detectable for many months and often averting preoperative localization and scheduling difficulties.