甲状腺未分化癌的综合治疗

甲状腺未分化癌是临床少见而发展快速的高度恶性肿瘤。调强放疗有利于局部病灶的控制,改善病人的生存质量。多个肿瘤中心在探索手术、放疗、化疗的综合治疗。     

Cytostatic drug therapy in anaplastic thyroid carcinoma

Anaplastic thyroid carcinomas are relatively rare and have a poor prognosis. In most cases, radical surgical procedures are impossible. Recently, a combination therapy of surgical resection, percutaneous irradiation, and chemotherapy has been described in the literature. After xenotransplantation in athymic nude mice, anaplastic thyroid carcinomas show the same histological features compared to the donors. By passing the tumor over several generations of nude mice, a constant growth rate has been observed. The model allows testing of therapeutic approaches in thyroid carcinoma tissues under in vivo conditions. In 2 different studies with 2 different anaplastic transplants, a statistically significant growth inhibition could be observed using doxorubicin therapy. In one study, combination therapy was performed. The results show no statistically significant difference in the group treated by doxorubicin alone. Further investigations, under in vivo conditions, will show whether a suitable combination therapy for anaplastic thyroid carcinoma can be developed.

---

Resumen Los carcinomas tiroideos anaplásicos son relativamente raros y tienen un mal pronóstico. En la mayoría de los casos, los procedimientos quirúrgicos radicales son imposibles. Recientemente, ha aparecido en la literatura una combinatión terapéutica de resectión quirúrgica, irradiatión percutánea, y quimioterapia. Después de xenotrasplante en ratones atímicos, los carcinomas anaplásicos muestran las mismas características que los tumores donantes. Mediante el paso a través de varias generaciones de ratones, se ha podido observar una tasa constante de crecimiento. El modelo permite probar los enfoques terapéuticos en tejidos carcinomatosos tiroideos en condiciones in vivo. En 2 estudios diferentes con 2 diferentes trasplantes anaplásicos, se pudo observar una inhibición estadísticamente significativa bajo terapia con doxorubicina. En un estudio se utilizó terapia combinada. Los resultados muestran que no hay diferencia significativa con el grupo tratado sólo con doxorubicina. Investigaciones adicionales, bajo condiciones in vivo, demostrarán si habrá de ser posible desarrollar un concepto adecuado de terapia combinada para los carcinomas anaplásicos de tiroides.

---

Résumé Les carcinomes anaplasiques thyroïdiens sont relativements rares et ont un mauvais pronostic. Dans la plupart des cas, des interventions chirurgicales radicales sont impossibles a réaliser. Récemment une association de la résection chirurgicale avec l'irradiation percutanée et chimiothérapique a été décrite dans la littérature. Après xénotransplantation chez la souris nue athymique, les carcinomes anaplasiques thyroïdiens montrent les mêmes caractères histologiques en comparaison avec les donneurs. Par passage sur plusieurs générations de souris, un taux de croissance constant a été observé. Ce modèle permet de tester les approches thérapeutiques en conditions in vivo dans le cadre des carcinomes du tissu thyroïdien. Au cours de 2 études différentes avec 2 transplants anaplasiques différentes, une inhibition statistiquement différente de la croissance a pu être observé avec des thérapeutiques utilisant de la doxorubicine. Dans une des études, une association thérapeutique a été réalisée. Ces résultats ne montrent aucune différence significative avec le groupe traité par la doxorubicine seule. De prochaines études montreront si au cours de conditions in vivo un concept convenable d'association thérapeutique peut être développé pour les carcinomes anaplasiques thyroïdiens.

---

---

Supported by Deutsche Forschungsgemeinschaft, We 1076 1-1/84.

---

Presented at the International Association of Endocrine Surgeons in Paris, September 1985.     

Anaplastic giant cell thyroid carcinoma.

Anaplastic (giant cell) thyroid carcinoma (ATC), is one of the most aggressive malignancies in humans with a median survival time after diagnosis of 3-6 months. Death from ATC was earlier seen because of local growth and suffocation. ATC is uncommon, accounting for less than 5 % of all thyroid carcinomas. The diagnosis can be established by means of multiple fine needle aspiration biopsies, which are neither harmful nor troublesome for the patient. The cytological diagnosis of this high-grade malignant tumour is usually not difficult for a well trained cytologist. The intention to treat patients with ATC is cure, although only few of them survive. The majority of the patients are older than 60 years and treatment must be influenced by their high age. We have by using a combined modality regimen succeeded in achieving local control in most patients. Every effort should be made to control the primary tumour and thereby improve the quality of remaining life and it is important for patients, relatives and the personnel to know that cure is not impossible. Different treatment combinations have been used since 30 years including radiotherapy, cytostatic drugs and surgery, when feasible. In our latest combined regimen, 22 patients were treated with hyper fractionated radiotherapy 1.6Gy x 2 to a total target dose of 46 Gy given preoperatively, 20 mg doxorubicin was administered intravenously once weekly and surgery was carried out 2-3 weeks after the radiotherapy. 17 of these 22 patients were operated upon and none of these 17 patients got a local recurrence. In the future we are awaiting the development of new therapeutic approaches to this aggressive type of carcinoma. Inhibitors of angiogenesis might be useful. Combretastatin has displayed cytotoxicity against ATC cell lines and has had a positive effect on ATC in a patient. Sodium iodide symporter (NIS) genetherapy is also being currently considered for dedifferentiated thyroid carcinomas with the ultimate aim of making radio-iodine therapy possible.     

Immunohistochemical reclassification of anaplastic carcinoma reveals small and giant cell lymphoma

Thirty-one cases of thyroid malignancies which were originally classified as anaplastic carcinoma were reexamined immunohistochemically using PAP methods (peroxidase:antiperoxidase) for IgM, IgG, IgA, cytoceratin, calcitonin, lysozyme and alpha-1-antitrypsin. The reclassification results were compared with patient data such as clinical symptoms, treatment modalities, and clinical outcome. Postoperative radiotherapy was carried out in more than 80% of cases, chemotherapy in none. Seven of 31 tumors showed a positive staining for IgM (n=4), IgG (n=2), and IgA (n=1) antibodies. All of these cases were negative for epithelial markers. Surprisingly, not only all small cell tumors (n=3) but also 4 tissues with predominantly giant cell areas were among those reclassified as primary malignant lymphoma.

---

Resumen Treinta y un casos de neoplasias malignas de la glándula tiroides originalmente clasificadas como carcinoma anaplásico fueron reexaminados por inmunohistoquímica utilizando métodos de peroxidosa:antiperoxidasa (PAP) para IgM, IgG, IgA, citoceratina, calcitonina, lisocina, y alfa-1-antitripsina. Los resultados de la reclasificación fueron comparados con la información clínica, incluyendo sintomatología, modalidades de tratamiento, y evolución final. Se realizó radioterapia postoperatoria en más de 80% de los casos, quimioterapia en ninguno. Siete de 31 tumores exhibieron tinción positiva para anticuerpos IgM (n=4), IgG (n=2), e IgA (n=1). Todos estos casos fueron negativos para marcadores epiteliales. Sorprendentemente, no sólo la totalidad de los tumores de células pequeñas (n=3) sino también 4 tejidos con áreas predominantes de células gigantes, estuvieron en el grupo de aquellos reclasificados como linfoma maligno.

---

Résumé Trente et un cas de tumeurs malignes de la thyroïde, classifiés à l'origine comme des carcinomes anaplasiques, ont été réexaminés en immunohistochimie pour la présence d'anticorps IgM, IgG, IgA, de cytocératine, calcitonine, lysocyme, et alpha1-antitrypsine en utilisant la méthode péroxydase/antipéroxydase. Les résultats de cette reclassification ont été comparés avec des données cliniques: symptômes cliniques, modalités thérapeutiques, et évolution clinique. On a employé la radiothérapie postopératoire dans 80% des cas et la chimiothérapie dans aucun cas. Sept des 31 tumeurs étaient positives pour les anticorps IgM (n=4), IgG (n=2), et IgA (n=1). Dans tous ces cas, les marqueurs épithéliaux étaient négatifs. De cette manière, on a pu reclasser comme lymphomes malins primitifs non seulement 3 tumeurs à petites cellules mais aussi 4 tumeurs avec des zones de cellules géantes.

---

---

Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.     

Analysis of long-term survivors in anaplastic thyroid carcinoma

We analyzed the clinicopathologic and therapeutic factors associated with long-term survival in 449 patients with anaplastic carcinoma registered with the Anaplastic Thyroid Carcinoma Consortium of Japan. Univariate analysis showed a significant relationship between long-term survival of more than 1 year and the following factors: the appearance of acute symptom; WBC < 10,000/mm3, tumor diameter < 5.0 cm; tumor remnant in the thyroid gland after surgery; no distant metastasis at initial diagnosi; complete resection of gross tumor; and administration of external irradiation (40 Gy) and chemotherapy. In multivariate analysis, only tumor diameter (< 5.0cm), complete resection of gross tumor, and external irradiation (40 Gy) showed a significant correlation with long-term survival. Only 31 of the 449 patients (7%) had these 3 factors, and 20 (65%) of them survived for more than 1 year. Among patients in any stage or with any prognostic index score who received little treatment, very few survived for more than 1 year. In contrast, many patients who received intensive combination therapy survived for more than 1 year. The results of this study suggest that sufficient intensive combination therapy has practical significance for patients with anaplastic carcinoma, except for those with advanced-stage disease.     

甲状腺未分化癌的治疗和预后

目的探讨甲状腺未分化癌的治疗方法和影响其预后的因素。方法对1970年5月至2005年5月间在本院治疗的50例甲状腺未分化癌患者的临床资料进行单因素(Kaplan-Meier法)和多因素分析(Cox比例模型)。结果共有50例患者,年龄27~80岁,其总的1、3、5年生存率分别为39·4%、29·6%和20·7%;中位生存时间是6个月;单因素分析显示首次就诊时的年龄<55岁、白细胞计数小于10·0×109个/L、无远处转移、接受放疗且剂量不小于40Gy、接受综合治疗者预后较好;多因素分析显示白细胞计数、是否接受手术加术后放疗是影响甲状腺未分化癌预后的独立因素。结论白细胞计数、是否接受手术加术后放疗是影响甲状腺未分化癌预后的独立因素;甲状腺未分化癌患者的预后极差,对这些患者根据个体情况进行积极的综合治疗特别是手术加术后放疗可能有利于提高其生存率。     

Multimodal therapy concepts in hepatocellular carcinoma

HCC is the most severe complication of liver cirrhosis. For the majority of patients the chances of cure are still limited. The recent experience in liver transplantation for HCC in the authors unit and in other centers allows the definition of a subgroup of patients, with small tumors (up to 3.0 cm, or 5 cm if solitary), no more than 3 nodules, and the absence of portal vein tumor thrombus. In these patients, liver transplantation offers a disease-free survival that is better than after liver resection, and similar to the survival of liver transplantation for benign liver disease. Patients with contraindications to transplantation, patients in whom a long waiting-time before transplantation is anticipated, and patients in countries with limited access to transplantation can be treated with a palliative intent (because of de novo tumors) by liver resection. Depending on liver function and local expertise, percutaneous ethanol injection (PEI) can be equally effective for small HCC. Other forms of treatment currently being evaluated, such as radio-frequency, thermal destruction or cyro-therapy, offer advantages similar to PEI without the need for multiple sessions. Further progress will probably come from a wider use of screening to detect a larger proportion of treatable lesions, and from strategies to prevent carcinogenesis in the cirrhotic liver, and possibly from innovative treatments such as gene therapy to alter the tumor biology.     

Clinical and histological differences in anaplastic thyroid carcinoma.

OBJECTIVE: To report our experience in patients with anaplastic thyroid carcinoma and try to establish differences between cases in which the histological study showed that there was an associated thyroid carcinoma and those that were strictly anaplastic or pure. DESIGN: Retrospective study. SETTING: University hospital, Spain. SUBJECTS: 14 patients with anaplastic thyroid cancer treated over a period of 26 years; 7 presented with associated thyroid tumours and 7 were pure. MEAN OUTCOME MEASURES: Clinical data (age, sex, symptoms), treatment, histological study (associated thyroid disease, spread, involved lymph nodes) and follow-up. RESULTS: 13 of the 14 tumours had spread locally. 5 patients were treated by total thyroidectomy, 3 subtotal thyroidectomy, 5 excision of the tumour, and 1 patient had a biopsy alone. There were associated thyroid tumours in 7 cases: 2 follicular, 2 tall cell papillary, 1 solid papillary, 1 medullary and 1 Hurthle cell tumour. 12 patients died. Another 2 are still alive having survived 61 and 70 months respectively, both with associated anaplastic cancers (follicular and solid). The mean survival was 14 months (24 for associated anaplastic carcinoma and 4 for pure anaplastic carcinoma). CONCLUSION: There is a subgroup of anaplastic cancers in which a better differentiated thyroid carcinoma coexists with the anaplastic carcinoma. The prognosis in this subgroup is better than that for primary pure anaplastic carcinoma.     

甲状腺未分化癌108例的治疗和预后分析

目的 探讨甲状腺未分化癌的临床生物学特性、治疗方法、预后以及影响预后的主要因素.方法 回顾性分析天津市肿瘤医院1981年1月-2009年4月收治的108例甲状腺未分化癌患者的临床及随访资料.结果 108例甲状腺未分化癌患者的中位生存时间为6个月;1年生存率为40.3％,2年生存率为30.9％,5年生存率21.9％.单因素分析显示,肿物最大径、远处转移、分期、白细胞数、放疗、原发灶切除加术后放疗、综合治疗是影响甲状腺未分化癌患者预后的因素.多因素分析显示,影响预后的独立因素为肿物最大径、分期、白细胞数、放疗.结论 甲状腺未分化癌发病率低,恶性度高,对此类患者应积极行综合治疗尤其是原发灶切除加术后放疗,即使失去手术机会的患者放疗仍能延长其生存期.     

The anaplastic thyroid carcinoma research consortium of Japan

Anaplastic thyroid carcinoma (ATC) is one of the most lethal neoplasia in humans, with a disease-specific mortality rate approaching 100%. ATC is uncommon and represents only 1-2% of all thyroid carcinomas. The aggressive nature and rarity of this disease make it difficult to improve the quality of evidence on it. To date, most existing knowledge of ATC is derived from single-institution studies with limited cohorts and short-term follow-up. To obtain further insights into this "orphan disease," we established the ATC Research Consortium of Japan (ATCCJ) in January 2009 as a multicenter registry that accumulates, analyzes, and reviews all information on ATC available in the country. As of July 2011, the ATCCJ database included 721 cases of ATC from 38 institutions. Using the database, the members of the ATCCJ have performed several retrospective studies, covering prognostic factors, therapeutic strategies, and pathologic features of ATC. Moreover, prospective trials are being planned as multicenter collaborations to determine the most beneficial treatment, with the ultimate purpose of improving the survival rate of patients with ATC.     

Multimodal therapy in locally advanced breast carcinoma

Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease.     

甲状腺未分化癌和甲状腺乳头状癌超声成像特征的对比研究

目的结合疾病病理特点,探讨甲状腺未分化癌和甲状腺乳头状癌超声成像特征的差异。 方法选取2010年1月至2015年6月在本院接受治疗并经病理证实为甲状腺未分化癌的患者12例为观察组,另选取同期经病理证实为甲状腺乳头状癌的患者35例为对照组,观察两组患者临床特征和超声特征。 结果女性患者所占比例大,观察组患者病灶平均直径大于对照组,纵横比<1的比例高于对照组,且观察组病灶微钙化程度高、血流少不规则、超声回声更不均匀、边界更为模糊,以上差异均有统计学意义（P<0.05）。两组患者超声特征中病灶形态、囊性变、回声、被膜受侵的对比差异无统计学意义。 结论甲状腺癌患者以女性为主,未分化癌患者病灶纵横比一般都<1且具有微钙化程度高、血流少不规则、超声回声更不均匀、边界更为模糊的特点,值得临床参考。     

Prognostic factors for Korean patients with anaplastic thyroid carcinoma

BACKGROUND: Anaplastic thyroid carcinoma (ATC), although rare, is one of the most aggressive human cancers, and patients with ATC have extremely poor prognoses despite various therapeutic measures. We wished to determine the prognostic factors of survival and effect of treatment on survival rate in patients with ATC. METHODS: We retrospectively reviewed the medical records of the 121 patients (41 men and 80 women) diagnosed with ATC from January 1995 to June 2004 at 5 major referral centers in Korea. RESULTS: Mean patient age at diagnosis was 64 +/- 11 years (range, 17-84 years). Of the 121 patients, 11 (9%) had intrathyroidal tumors, 69 (57%) had extrathyroidal tumors or lymph node involvement, 29 (24%) had distant metastases, and 12 had no data about staging (9%). The mean tumor diameter was 5.5 +/- 2.5 cm (range, 0.5-17.0 cm). At a median follow-up of 41 months (range, 26-122 months), 8 patients were alive. Median survival time was 5.1 months. The disease-specific survival rates were 42% at 6 months, 16% at 12 months, and 9% at 24 months. Sixteen patients (13%) received only supportive care, 25 (21%) received surgery alone, 20 (16%) received radiation treatment or chemotherapy without surgery, and 60 (50%) received surgery plus radiation treatment or chemotherapy. Multivariate analysis showed that age less than 60 years, tumor size less than 7 cm, and lesser extent of disease were independent predictors of lower disease-specific mortality. CONCLUSIONS: Long-term survival is possible for ATC patients less than 60 years old and with small localized tumors. Although aggressive multimodal therapy, including surgery, radiation treatment, and chemotherapy, was not significantly associated with improved survival, we advocate aggressive multimodal therapy in selected ATC patients with good prognostic factors.     

The important role of operations in the management of anaplastic thyroid carcinoma

BACKGROUND: Anaplastic thyroid carcinoma is a rare and highly lethal neoplasm. We investigated whether operations have an impact on the survival of patients who have anaplastic carcinoma without distant metastasis. METHODS: Between 1989 and 1999, 40 consecutive patients with anaplastic carcinoma, without distant metastasis at the time of presentation or during local treatment, were reviewed. The cumulative survival rates and 1-year survival rates were compared. RESULTS: Eleven patients had a small focus of anaplastic carcinoma in a differentiated carcinoma, and 29 patients had ordinary anaplastic thyroid carcinoma. Surgical debulking was performed in 26 patients. Radiotherapy was used for 31 patients and chemotherapy for 19 patients. The 1-year survival rates of the patients with incidental anaplastic carcinoma, ordinary anaplastic carcinoma who underwent operations, and ordinary anaplastic carcinoma who did not undergo operations were 73%, 60%, and 21%, respectively. A significantly higher cumulative survival rate was observed in patients with incidental anaplastic carcinoma than in those with ordinary anaplastic carcinoma. A significantly better outcome was obtained by surgical debulking of ordinary anaplastic carcinoma. CONCLUSIONS: Patients with incidental anaplastic carcinoma tended to have a good outcome, but some had a poor prognosis. Surgical debulking improved the outcome of patients with ordinary anaplastic carcinoma.