307例女性乳腺髓样癌报告

本文总结了３０７例经治的中国女性乳腺髓样癌。根据Ｒｉｄｏｌｆｉ等制定的诊断标准（ｃａｎｃｅｒ，１９７７，４０：１３６５～１３８６），分为９２例（２９．９％）典型髓样癌和２１５例（７０．０％）非典型髓样癌。结果表明９２例典型髓样癌和２１５例非典型髓样癌的１０年生存率分别为８４．８％（７８／９２）和７３．０％（１５７／２１５）。腋窝淋巴结的转移情况被认为是影响预后的重要因素，在腋窝淋巴结无转移组５６例典型髓样癌和１１４例非典型髓样癌的１０年生存率分别为９２．９％（５２／５６）和８６．０％（９８／１１４），而在腋窝淋巴结有转移时分别为７２．２％（２６／３６）和４９．５％（５０／１０１）。乳腺髓样癌具有良好的组织学特征和预后效果，特别是腋窝淋巴结阴性的典型髓样癌的预后效果最佳。     

乳腺髓样癌的治疗

目的探讨乳腺髓样癌临床特征、治疗和预后。方法回顾性分析1995年1月至1999年12月收治的乳腺髓样癌的临床资料。结果26例乳腺髓样癌占同期治疗女性乳腺癌616例的4.2%,年龄31~66(45.8±10.6)岁,肿瘤大小1~5 CM,腋淋巴结阳性率23.1%,腋淋巴结转移的发生与乳腺肿瘤的大小无关,免疫组化检测雌激素(ER)、孕激素(PR)和HER-2/NEU的阳性率分别为26.3%、21.1%和5.3%。全组进行手术和辅助化疗(环磷酰胺、甲氨蝶呤和氟尿嘧啶)。5例服用三苯氧胺,3例进行放射性治疗。随访时间5~9年,平均7.5年,总的5年生存率为88.4%。结论乳腺髓样癌的预后较好,手术加辅助性化疗是治疗的重要手段,分子生物学指标在乳腺髓样癌预后中的作用应该受到足够的重视。     

乳腺典型髓样癌临床分析

目的:研究乳腺典型髓样癌的临床特征和预后。方法:分析发病年龄、肿块大小、部位、淋巴结转移与生存率关系。结果:本文58例典型髓样癌占同组女性乳腺癌的3.1%。平均发病年龄52.6岁,腋淋巴结转移率30.9%,五年和十年生存率分别为87.9%、85.2%。结论:典型髓样癌属较低度恶性肿瘤,预后较好。但也有个别病例死于脑转移。     

乳腺髓样癌的临床病理特点及治疗

目的 探讨乳腺髓样癌的临床病理特点、诊治和预后.方法 回顾性分析7年间收治的28例乳腺髓样癌的临床资料.全组进行手术和辅助化疗(环磷酰胺+阿霉素、紫杉醇+阿霉素).5例内分泌治疗,8例进行放射性治疗.结果 28例乳腺髓样癌占同期治疗956例女性乳腺癌的2.9%;年龄28～96(50.68 4±12.63)岁;肿瘤大小1～5 cm;腋淋巴结阳性率47.6%;肿瘤淋巴细胞浸润率100%.免疫组化检测雌激素受体(ER),孕激素受体(PR),HER-2/neu,p53的阳性率分别为35.7%,32%,32%,67.9%.术后中位随访时间为42个月(1个月至6年),总生存率为100%.结论 乳腺髓样癌的预后较好.选择合理的外科手术及辅助化疗可取得较满意的效果.分子生物学指标在乳腺髓样癌治疗和预后的作用应该受到足够重视.     

乳腺髓样癌的超声造影特征与病理对照

目的分析乳腺髓样癌的超声造影特征,并与病理学对照。方法回顾性分析13例乳腺髓样癌患者的超声造影形态学特征,比较造影前后肿块横径、肿块与周围乳腺正常组织的时间-强度曲线定量参数,并进行统计学分析。将超声造影表现与病理表现相对照。结果乳腺髓样癌超声造影显示肿块形态不规则、边界清晰、内部均匀增强分别为10、11、11例,与病理形态学特征相符合。造影前后肿块横径差异无统计学意义(P=0.61),与病理学膨胀性生长方式相符合。与周围乳腺正常组织相比,髓样癌造影剂到达时间和达峰时间显著提前(P=0.034、0.021),峰值强度显著提高(P=0.005),与病理学上病灶内血管密度增高且分布均匀、病灶周边有较大管径血管的特征相符合。结论乳腺髓样癌特征性的超声造影表现有其病理学依据,可作为临床超声诊断和鉴别诊断的依据。     

乳腺髓样癌90例临床分析

目的探讨乳腺髓样癌的临床特点、治疗及预后。方法回顾性分析90例乳腺髓样癌的临床资料:肿瘤直径(4.1±2.2)cm,左侧49例,右侧41例,21例有腋淋巴结肿大,其中19例术前误诊为良性肿瘤而行局部切除,术中冰冻切片确诊53例,术前细针穿刺确诊18例。行乳癌根治术(Hal-sted法)49例,改良根治术41例,其中保留胸大肌的改良根治术Ⅰ式(Patey手术)29例,保留胸大小肌的改良根治术Ⅱ式(Auchinc loss手术)12例。21例腋淋巴结肿大者行术前辅助化疗,术后均行化疗。结果确诊典型和不典型髓样癌各45例,其腋淋巴结转移率无区别。均获随访,时间5.8(1.5~11)年,3年、5年生存率分别为95.6%和88.9%。结论乳腺髓样癌预后较好,术前应行细针穿刺细胞学检查和术中冰冻切片检查,手术加辅助化疗是治疗的重要手段。     

甲状旁腺素对人甲状腺髓样癌细胞增殖和凋亡的影响

目的探讨甲状旁腺素对人甲状腺髓样癌细胞体外增殖抑制及凋亡作用。方法体外培养甲状腺髓样癌细胞株,经甲状旁腺素和甲状旁腺素受体单抗干预处理后,倒置相差显微镜下观察细胞生长状况,流式细胞仪检测细胞凋亡。结果倒置相差显微镜下细胞变化明显,各浓度的甲状旁腺素和甲状旁腺素受体单抗均分别能有效地抑制甲状腺髓样癌细胞增殖、诱导细胞凋亡,凋亡作用呈时间和浓度依赖。当甲状旁腺素浓度为2．0μmol／L、甲状旁腺素受体单抗浓度为1．0μmol／L时,对细胞凋亡作用显著（P〈0．05）,凋亡率分别为13．24％及20．78％。结论甲状旁腺素对人甲状腺髓样癌细胞增殖有抑制作用并能诱导其凋亡。     

甲状腺髓样癌15例诊治分析

目的 提高甲状腺髓样癌的术前诊断率.方法 回顾性分析15例甲状腺髓样癌的临床资料.结果 髓样癌除合并内分泌综合征者外,绝大多数与其他类型甲状腺癌相似,多以颈部肿块就诊,术前确诊困难,误诊率较高;多数系术中冰冻病理或术后病理确诊.结论 甲状腺髓样癌术前确诊困难,因此我们应采取以测定血清降钙素为主等一系列检测手段来作为甲状腺髓样癌的术前诊断程序.     

甲状腺髓样癌13例临床分析

甲状腺髓样癌是甲状腺癌中较少见的病理类型 ,临床与病理有其特殊性。本文就我院 1985～ 2 0 0 0年间收治的甲状腺髓样癌 13例临床资料 ,诊断及治疗问题分析讨论如下。临床资料1.一般资料 :甲状腺癌 3 5 0例 ,其中髓样癌 13例 (3 .7% )。在髓样癌中男性 5例 ,女性 8例 ,年龄 40～ 65岁 ,平均年龄 5 1岁。临床表现 :病程 6个月～ 11年 ,1～ 5年内 7例 ,7年以上 6例。 5例甲状腺包块逐渐增大 ,4例有甲状腺包块伴有颈部转移性包块 ,4例有甲状腺包块伴有声音嘶哑呼吸困难。 13例中仅有 1例并顽固性腹泻 ,开始每日 2～ 3次 ,以后逐渐增至每日7～ …     

散发性甲状腺髓样癌术式选择及预后分析

散发性甲状腺髓样癌是甲状腺髓样癌的主要类型,尽管临床少见,但预后较差。手术是治疗散甲状腺发性髓样癌的主要手段,不规范的手术会导致肿瘤和转移淋巴结残留,增加复发风险,降低治愈率和存活率。全甲状腺切除和双侧中央区淋巴结清扫及治疗性颈侧区淋巴结清扫是治疗散发性甲状腺髓样癌的主要手术方式,在无明确影像学证据情况下,不推荐预防性颈侧区淋巴结清扫。年龄、肿瘤大小、淋巴结转移、腺外侵袭、远处转移、手术方式、RET基因突变、血清降钙素和CEA水平是影响散发性甲状腺髓样癌预后的危险因素。     

Medullary Carcinoma of the Thyroid Gland

Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor that has attracted a great deal of interest because of its frequent presentation as a familial tumor and its primary involvement in the type II multiple endocrine neoplasia (MEN) syndromes MEN-IIA and MEN-IIB and familial medullary thyroid carcinoma (FMTC). The MTC tumor cells secrete the polypeptide hormone calcitonin, which serves as an excellent tumor marker, useful for defining the presence of disease, preoperatively or following thyroidectomy. The discovery that mutations in the RET proto-oncogene are associated with MEN-II syndromes was highly significant in that it demonstrated a clear correlation between genotype and phenotype; and most importantly it provided a mechanism whereby family members at risk could be identified by direct DNA analysis. Virtually all patients with MEN-IIA, MEN-IIB, and FMTC develop MTC; therefore there is a clear rationale for performing thyroidectomy as soon as a RET mutation has been identified. Because MTC appears to be much more aggressive in patients with MEN-IIB, thyroidectomy is performed during the first year of life in this setting, whereas in patients with MEN-IIA, where the tumor appears to be more indolent, the procedure can be safety delayed until age 5 years. Reoperative neck exploration in patients with evidence of persistent or recurrent MTC has been effective in a significant number of patients, although the success of the operation requires careful patient selection and preoperative assessment. MTC, as expressed in the MEN-II syndromes, is an excellent model to evaluate the usefulness of interventional therapy in patients demonstrated to have a genetic predisposition for cancer.     

甲状腺髓样癌的外科治疗

虽然甲状腺癌是人体内分泌系统中最常见的恶性肿瘤，但甲状腺髓样癌并不多见，约占甲状腺癌的3％～10％。我科2005年共收治甲状腺癌患者542例，甲状腺髓样癌仅18例，占3．3％。甲状腺髓样癌是来自于甲状腺滤泡旁细胞（亦称C细胞）的一种恶性肿瘤。甲状腺滤泡旁细胞为神经内分泌细胞，亦属APUD（amine precursor uptake and dccarboxylation）系的细胞，即胺前身摄取和脱羟细胞，该细胞的主要特征为分泌降钙素及多种物质包括癌胚抗原（CEA），并产生淀粉样物。     

Prognostic Factors for Sporadic Medullary Thyroid Carcinoma

Introduction Medullary thyroid carcinoma (MTC) originates from the thyroid parafollicular cells and accounts for 3% to 10% of all thyroid malignancies. Approximately 84% of cases are sporadic. The aim of this study was to evaluate the outcomes of treatment for sporadic medullary thyroid carcinoma (SMTC) and define the prognostic factors for overall survival. Methods The records of 32 SMTC patients treated at Ankara Oncology Education and Research Hospital between September 1993 and April 2003 were retrospectively evaluated. The effects of age, gender, tumor localization, extent of the primary surgical resection, tumor size, capsule invasion, lymph node metastasis, extranodal extension, tumor stage, local recurrence, and distant metastasis on the overall survival rate were evaluated by univariate and multivariate analyses. Results There were 32 patients (19 females, 13 males) with a median age of 45 years (21–76 years). Altogether, 22 patients had undergone complete resection and 10 patients incomplete resection. The median follow-up was 48 months (9–111 months), and the overall 5-year survival rate was 51%. Based on the univariate analysis, the extent of primary surgical resection, pathologic tumor size, capsule invasion, lymph node invasion, extranodal extension, tumor stage, local recurrence, and distant metastasis were factors that significantly affected survival. In the multivariate analysis, however, only the extent of the primary surgical resection, capsule invasion, and distant metastasis were found to be statistically significant factors. Conclusions The extent of the primary surgical resection significantly influences the survival of patients with SMTC. Capsule invasion and distant metastasis were additional factors affecting the prognosis.     

Long-term Outcome of Reoperations for Medullary Thyroid Carcinoma

Background Most patients with medullary thyroid carcinoma (MTC) have persistent disease after primary surgery, as evidenced by calcitonin elevation. Previous reports showed that reoperation on selected patients yields immediate calcitonin normalization in one-third of patients. Long-term follow-up data are needed to assess the outcome in such patients. This report aims to provide 8– to 10–year follow-up on reoperations for persistent or recurrent MTC. Methods An Internal Review Board (IRB) approved database on patients treated for MTC has been prospectively maintained. This database was reviewed to report follow-up data on calcitonin levels and survival. Results Between 1992 and 2006, 148 patients underwent reoperations for recurrent or persistent MTC (55 patients had 59 reoperations for palliation, and 93 patients had 105 reoperations for cure). Of the 93 patients operated on for cure (44 with hereditary MTC, 49 with the sporadic form), 8–10-year follow-up data were available on 56. Four patients died of disease (4.3% of 93). Two died of unrelated causes, and were excluded from calcitonin outcome analysis. Fourteen patients of 54 (26.0%) have unstimulated calcitonin levels of < 10 pg/ml at 8–10 years. Eleven additional patients (20.4%) have levels < 100 pg/ml. None of these 25 patients (46.4%) have radiologic recurrence. Conclusions Previous reports demonstrated the low morbidity of reoperation for MTC in experienced hands, and success was determined by lowering of calcitonin levels. Follow-up data demonstrate that at least one third of such patients have long-term eradication of their disease following reoperation, as evidenced by biochemical and imaging studies.     

Medullary Thyroid Carcinoma: Ethical Issues for the Surgeon

Medullary thyroid cancer is a disease with an established genetic inheritance pattern for which evidence-based guidelines recommend genetic testing and subsequent management of affected patients and their family members. The perceived stigma of genetic testing, coupled with issues involving confidentiality and disclosure, create potential conflict and confusion. In some cases, there is a need for genetic testing and prophylactic surgery in children, augmenting the need for a judicious approach that balances respect for individual autonomy and parental rights with the best interest of the child. We provide an overview of the ethical issues facing surgeons caring for patients with familial medullary thyroid carcinoma, and recommend interventions and resources to assist in decision making in these difficult situations.     

Latent Subclinical Medullary Thyroid Carcinoma: Diagnosis and Treatment

n = 11), palpable metastatic lymph node ( n = 6), distant metastases ( n = 4). In nine cases the diagnosis was made by both fine-needle aspiration cytology and serum CT measurement. In the four other cases the initial cytology was incorrect, but the diagnosis was revised on the basis of elevated basal CT values. In 11 patients (group 2) presenting with nodular thyroid disease, SMTC was not clinically detectable. SMTC was preoperatively suspected by elevated CT levels: basal CT > 10 pg/ml and pentagastrin-stimulated CT peak > 100 pg/ml. One patient in group 1 with distant metastases was not operated on. All of the other 12 patients underwent total thyroidectomy and extensive lymph node dissection. The mean size of the tumors was 27 mm. Lymph node involvement was found in nine patients. After surgery, CT levels returned to normal in five patients but remained elevated in five others; the two remaining patients died of distant metastases. All 11 patients in group 2 underwent total thyroidectomy and central neck dissection. None of the 11 patients had nodal extension. All 11 patients are biochemically cured. It was concluded that routine measurement of basal serum CT in those with nodular thyroid disease allows early, preoperative diagnosis of subclinical SMTC and improves the results of surgery.     

甲状腺髓样癌35例治疗体会

目的总结甲状腺髓样癌(medullary thyroid carcinoma,MTC)临床特征及治疗方法。方法回顾分析1997年1月~2005年12月经治的35例MTC的临床及病理资料。结果35例均予手术切除原发灶并加行颈淋巴结清扫术,术后放疗5例,化疗7例。所有病例均经病理证实为MTC,淋巴结转移率为51.4%。32例术后随访2~10年,5年生存率为87.5%。结论MTC治疗应以根治性切除为原则,切除范围应比其他类型的甲状腺癌积极,术后可以辅以多种非手术治疗。     

Genotype-Phenotype Based Surgical Concept of Hereditary Medullary Thyroid Carcinoma

Background Since DNA tests have enabled reliable identification of asymptomatic RET (rearranged during transfection) gene carriers, myriads of publications have appeared on genotype-phenotype relationships. A comprehensive appraisal of this body of evidence using evidence-based methodology is pending. Methods This study was based on systematic evaluation of the literature using evidence-based criteria. Results (1) There is a distinct age-related progression of hereditary medullary thyroid carcinoma (MTC) in carriers of RET mutations (grade C). (2) Among the high-risk RET mutations, those in codon 634 cause higher penetrance rates of the multiple endocrine neoplasia 2A phenotype (MTC, pheochromocytoma, and parathyroid hyperplasia/adenoma) than mutations in codons 609, 611, 618, and 620, irrespective of the amino acid substituting for cysteine (grade C). (3) DNA-based screening is superior to calcitonin-based screening in asymptomatic RET carriers (grade C). (4) Using a worst-case scenario, i.e., considering the earliest finding of MTC in asymptomatic RET carriers, pre-emptive thyroidectomy should be performed before that time (grade C) to be truly prophylactic. Specifically, for carriers of highest-risk mutations (codon 918): within the first year of life; for carriers of high-risk mutations (codon 609, 611, 618, 620, 630, and 634): before the age of 5 years; and for carriers of least-high risk mutations (codon 768, 790, 791, 804, and 891): before the age of 5-10 years. Strict adherence to these grade C recommendations can result in undertreatment of the former (codon 634) and overtreatment of the latter. Conclusions These genotype-phenotype correlations provide a solid foundation on which to base surgical concepts, leaving little room for randomized controlled clinical trials.     

Medullary Thyroid Carcinoma: Long-Term Outcomes of Surgical Treatment

Background

Medullary thyroid carcinoma (MTC) accounts for 5 to 10% of all thyroid cancers but is responsible for a disproportionate number of deaths.

Methods

We performed a retrospective review to describe clinical outcomes in patients with medullary thyroid carcinoma, screening a subset of patients for somatic mutations in the RET and p18 genes and performing genotype-phenotype correlation in a tertiary-care referral hospital from 1967 to 2009.

Results

We studied a total of 94 patients identified from a prospectively maintained thyroid cancer database. Data gathered included patient demographics, serum calcitonin, clinical outcomes, histopathology, genetic analysis, and status at final follow-up. A subset cohort (n = 50) was screened for somatic mutations in the RET gene and the three exons of the p18 gene. The subset cohort was composed of hereditary medullary thyroid carcinoma (HMTC) (n = 19, index patients = 10, screen detected = 9) and sporadic medullary thyroid carcinoma (SMTC) (n = 31). There were no mutations in the p18 gene in the subset cohort.

Conclusions

A total of 67 SMTC and 27 (28.7%) HMTC cases identified. SMTC were older at initial presentation (52 vs. 34, P = 0.003), had higher preoperative serum calcitonin levels (7968 vs. 1346 ng/L, P = 0.008), and had lymph node recurrence (P = 0.001) compared to HMTC. The tumors were smaller in HMTC (P = 0.038). Overall 10-year survival in SMTC versus HMTC was 69 versus 93% (P = 0.12). On multivariate analysis, vascular invasion (hazard ratio 6.4, P = 0.019) was an adverse predictor for disease-free survival. HMTC in the era of RET analysis presents with a smaller primary tumor, lower preoperative serum calcitonin levels, and lower rates of lymph node metastasis. Mutations in the p18 gene were not a major factor in medullary thyroid carcinoma tumorigenesis.