Choriocarcinoma in a patient with human immunodeficiency virus: case presentation and review of the literature

A 26-year-old woman with choriocarcinoma and acquired immunodeficiency syndrome initially presented with hydatidiform mole and was treated with dilation and curettage. Because of persistent elevation of serum beta human chorionic gonadotropin, the patient was treated with combination chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMACO) for high-risk gestational trophoblastic tumor. The patient s initial stage was IIc. The serum beta human chorionic gonadotropin level returned to normal. Fourteen months later, the gonadotropin level again increased. The patient was treated with uterine curettage followed by vaginal hysterectomy. Despite further chemotherapy (with methotrexate and leucovorin, then oral etoposide), she died following metastasis of the tumor to the brain. Only four other cases of human immunodeficiency virus (HIV) infection with choriocarcinoma have been reported. There is no evidence to date that gestational trophoblastic disease is more prevalent in patients with acquired immunodeficiency syndrome. HIV infection and other immunodeficiency states, however, can influence the course of treatment and outcome in these patients. The low CD4 count in HIV infection may lead to a poor outcome despite chemotherapy.     

Pharmacotherapy of gestational trophoblastic disease

Gestational trophoblastic neoplasms are the most responsive of all solid tumours to chemotherapy leading to an overall cure rate of > 90%. Nonmetastatic disease (FIGO Stage I) and low-risk metastatic disease (FIGO Stages II and III; WHO score < 7) can be treated with single-agent methotrexate or actinomycin D protocols resulting in a survival rate approaching 100%. Metastatic high-risk disease (FIGO Stage IV or WHO score > 7) should be treated with initial intensive multimodality therapy with combination chemotherapy, consisting of etoposide, high-dose methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) and adjuvant radiotherapy and surgery when indicated. Despite this aggressive approach, ～ 30% of patients with high-risk disease will fail initial therapy or relapse from remission. Salvage chemotherapy with drug regimens containing platinum agents and etoposide, usually in conjunction with bleomycin or ifosfamide, as well as surgical resection of sites of resistant disease, will ultimately result in a survival rate of 80 – 90% for metastatic high-risk disease.     

Pharmacotherapy of gestational trophoblastic disease

Gestational trophoblastic neoplasms are the most responsive of all solid tumours to chemotherapy leading to an overall cure rate of > 90%. Non-metastatic disease (FIGO Stage I) and low-risk metastatic disease (FIGO Stages II and III; WHO score < 7) can be treated with single-agent methotrexate or actinomycin D protocols resulting in a survival rate approaching 100%. Metastatic high-risk disease (FIGO Stage IV or WHO score > 7) should be treated with initial intensive multimodality therapy with combination chemotherapy, consisting of etoposide, high-dose methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) and adjuvant radiotherapy and surgery when indicated. Despite this aggressive approach, approximately 30% of patients with high-risk disease will fail initial therapy or relapse from remission. Salvage chemotherapy with drug regimens containing platinum agents and etoposide, usually in conjunction with bleomycin or ifosfamide, as well as surgical resection of sites of resistant disease, will ultimately result in a survival rate of 80 - 90% for metastatic high-risk disease.     

Livin在妊娠滋养细胞肿瘤中的表达及意义

目的通过检测凋亡抑制蛋白Livin在妊娠滋养细胞肿瘤组织中的表达,并讨论与妊娠滋养细胞肿瘤的临床特征的相关性,为妊娠滋养细胞疾病提供新的诊断及治疗思路。方法采用免疫组织化学SABC法检测Livin在22例妊娠滋养细胞组织（14例侵蚀性葡萄胎,8例绒毛膜癌）中的表达,并以10例正常早孕绒毛组织作对照组。结果Livin蛋白在侵蚀性葡萄胎中表达率为57.1%,绒毛膜癌中表达率为87.5%,正常绒毛组织中为10.0%;Livin蛋白在妊娠滋养细胞肿瘤中的高表达与正常绒毛组织中的表达差异具统计学意义（P＜0.05）。在妊娠滋养细胞肿瘤患者中Livin蛋白的表达与其临床分期明显相关（P＜0.05）。结论Livin在侵蚀性葡萄胎、绒癌中高表达提示Livin可能参与了妊娠滋养细胞肿瘤的发生、发展。     

妊娠性滋养细胞疾病中EGFR与NM23表达的研究

目的：探讨表皮生长因子受体（EGFR）与NM23在滋养细胞疾病发生发展过程中的作用。方法：以免疫组化法检测了82例妊娠性滋养细胞疾病患者及10例正常胎盘组中EGFR和NM23的表达水平。结果：亚性滋养细胞肿瘤与葡萄胎相比,EGFR表达水平明显减低。NM23表达水平与正常妊娠早期绒毛相近,与滋养细胞增生程度无关,但在恶性滋养细胞肿瘤中NM23表达水平明显下降,且在肿瘤早期即可出现,结论：EGFR与NM23在恶性滋养细胞肿瘤中两者一致性减低,提示这种减低可能在滋养细胞肿瘤的发生及恶性转化中有协同作用。     

低凋亡指数与高端粒酶活性的葡萄胎与GTT关系的研究

目的研究葡萄胎的凋亡指数及端粒酶活性与妊娠滋养细胞肿瘤的相关关系。方法对142例葡萄胎及8例妊娠滋养细胞肿瘤采用S-P法及Evision法检测PCNA、Ps,、Ki-67、FADD、端粒酶活性的表达。结果142例葡萄胎中PCNA阳性率为14．08％（20／142）、P535．63％（8／142）、Ki-67阳性率5．63％（8／142）、FADD59．15％（84／142）、端粒酶阳性率10．56％（15／142）。5例侵袭性葡萄胎中PCNA阳性率80％（4／5）、Ki-67阳性率80％（4／5）、P53阳性率100％（5／5）、FADD阳性率0％（0／5）、端粒酶阳性率100％（5／5）。3例绒毛膜癌中PCNA阳性率100％（3／3）、P53阳性率100％（3／3）、Ki一67阳性率100％（3／3）、FADD阳性率33．3％（1／3）、端粒酶阳性率66．7％（2／3）。结论低凋亡指数与高端粒酶活性的葡萄胎可能是发展为妊娠滋养细胞肿瘤的高危因素。端粒酶的激活能够促进细胞增殖和恶性进展,抑制端粒酶活性能够起到抑制细胞增殖的作用。     

E-钙粘素在妊娠滋养细胞疾病的表达及其对葡萄胎恶变预测的价值

目的 探讨E-钙粘素在妊娠滋养细胞疾病的表达及其对葡萄胎恶变预测的价值.方法 应用免疫组化SP法检测22例正常早孕绒毛和55例妊娠滋养细胞疾病石蜡包埋组织中E-钙粘素的表达情况,结合临床资料进行结果分析.结果 E-钙粘素在正常早孕绒毛和非恶变葡萄胎的表达差异无显著性(P>0.05);恶变葡萄胎、侵蚀性葡萄胎和绒癌的表达量明显低于正常早孕绒毛和非恶变葡萄胎(P<0.05);侵蚀性葡萄胎和绒癌的表达量低于恶变葡萄胎(P<0.05).葡萄胎恶变与E-钙粘素的表达呈负相关(P<0.05);与血β-HCG值、卵巢黄素化囊肿呈正相关(P<0.05).结论 E-钙粘素的表达下调可能是滋养细胞恶性转化的早期事件,在妊娠滋养细胞疾病的恶化进展中起重要作用;E-钙粘素可作为葡萄胎恶变预测的参考指标.     

VMP方案治疗Ⅲ期妊娠滋养细胞肿瘤疗效分析

目的探讨甲氨蝶呤、顺铂联合长春新碱(VMP)方案治疗Ⅲ期妊娠滋养细胞肿瘤的疗效及安全性。方法 2007年1月—2011年5月,在安徽省立医院接受VMP方案化疗的Ⅲ期妊娠滋养细胞肿瘤患者共52例,回顾性分析这些患者的临床资料,观察该方案治疗的疗效及安全性。结果 52例Ⅲ期妊娠滋养细胞肿瘤患者共接受244个疗程的VMP方案化疗(其中包括86个疗程的巩固治疗),平均疗程4.69个;低危者完全缓解率达100%,高危者达81.8%;主要毒副反应包括骨髓抑制、消化道反应和口腔溃疡等,无严重毒副反应发生。结论 VMP方案用于Ⅲ期妊娠滋养细胞肿瘤治疗,是一种安全有效的方案。     

以甲状腺功能亢进为首发表现的葡萄胎1例

葡萄胎（HM）是一种异常的人类妊娠,可将其分为完全性葡萄胎（CHM）和部分性葡萄胎（PHM）。其主要临床表现为停经后阴道不规则流血、子宫异常增大、妊娠呕吐、腹痛、卵巢黄素化囊肿及甲状腺功能亢进征象等,其中甲状腺功能亢进临床表现少见。我们报道1例以间断性怕热、多汗、心悸、消瘦为主要临床表现的育龄期女性患者,常规抗甲状腺药物治疗无效,后经阴道B超、血HCG检查诊为CHM。清宫术后患者临床症状好转,甲状腺功能完全恢复正常,从而证实甲状腺功能亢进继发于CHM。因此,临床医生对于育龄期女性甲状腺功能亢进患者,在排除甲状腺性、垂体性以及医源性因素后,应注意葡萄胎及其他妊娠滋养细胞疾病等妇科情况及疾病。     

高危因素对葡萄胎后恶变的影响临床分析

目的：分析有恶变高危因素的葡萄胎患者的临床特点,为提高妊娠滋养细胞肿瘤（GTN）的诊治手段提供借鉴。方法回顾性分析该院妇产科2007年1月至2013年12月162例在行清宫术后病理检查诊断为葡萄胎患者的临床资料,观察GTN的临床表现、治疗效果等,比较有高危因素与无高危因素葡萄胎后GTN患者的临床特点。结果162例葡萄胎患者中,有46例恶变,其中有高危因素患者36例,无高危因素患者10例。比较两类患者恶变率、临床表现及治疗后效果,早期葡萄胎合并高危因素患者恶变率及临床表现与无合并高危因素患者比较,差异均有统计学意义（P＜0.05）;葡萄胎后GTN患者治疗效果比较,差异无统计学意义（P＞0.05）。结论葡萄胎恶变率与患者发病年龄、子宫大小、卵巢黄素囊肿等高危因素有关。因此,对患者高危因素进行正确评估,对临床早期预测葡萄胎恶变及给予预防性化疗有一定指导意义,也有助于诊治GTN和提高临床疗效。     

Therapy for osteosarcoma: where do we go from here?

Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. Current optimal treatment for osteosarcoma consists of multi-agent chemotherapy and aggressive surgical resection of all sites of disease involvement. The current national and international cooperative trial for patients with newly diagnosed osteosarcoma builds upon the backbone of cisplatin, doxorubicin, and methotrexate. This protocol is designed to clarify whether (i) the addition of ifosfamide and etoposide to postoperative chemotherapy with cisplatin, doxorubicin, and methotrexate improves the event-free survival and overall survival for patients with resectable osteosarcoma and a poor histologic response to 10 weeks of preoperative chemotherapy; and (ii) the addition of pegylated interferon-alpha-2b as maintenance therapy after postoperative chemotherapy with cisplatin, doxorubicin, and methotrexate improves the event-free survival and overall survival for patients with resectable osteosarcoma and a good histologic response to 10 weeks of preoperative chemotherapy. However, the optimal treatment strategy (or strategies) for patients with relapsed or metastatic disease has yet to be defined. This remains one of the persistent challenges in the treatment of osteosarcoma.Recent therapeutic advances have focused on circumventing chemotherapy resistance mechanisms, incorporation of non-classical agents into upfront therapy, targeting of the tumor micro-environment, and investigating the role of novel delivery mechanisms.In patients with localized disease the 5-year survival rate is at least 70%; patients with metastatic or recurrent disease have <20% chance of long-term survival despite aggressive therapies. These figures have changed little in the past 2 decades. This review focuses on the current therapy for osteosarcoma, and highlights emerging strategies that will hopefully change the outlook for patients with this disease.     

Pharmacokinetic evaluation of gemcitabine hydrochloride for the treatment of cervical cancer

INTRODUCTION: Cervical cancer is the third most prevalent cancer in females worldwide. When advanced, the disease requires primary radiation concurrent with chemotherapy. However, chemotherapy alone is the standard treatment for recurrent/persistent/metastatic disease. AREAS COVERED: Areas covered in this review include the treatment of advanced cervical cancer with gemcitabine as radiosensitizer, either alone or in combination with cisplatin. The use of gemcitabine for recurrent/persistent/metastatic cervical cancer is also reviewed. EXPERT OPINION: Statistically significantly better survival rates are achieved with cisplatin doublets against cisplatin alone, in the management of recurrent/persistent/metastatic cervical cancer. The choice of the cisplatin doublet with paclitaxel, vinorelbine, gemcitabine and topotecan arms should be based on physician preference, pre-existing morbidity and patient-related factors. In advanced disease, a recently reported Phase III trial establishes the novel regimen of concurrent gemcitabine plus cisplatin and external radiation, followed by brachytherapy and two adjuvant 21-day cycles of gemcitabine plus cisplatin, as significantly improving survival outcomes when compared with the current standard of care. The increased acute toxicity of this regimen is clear; however, this should not deter its incorporation into clinical practice, in that the toxicity is predictable and manageable; nevertheless, the occurrence of late toxicity and survival at longer follow-up time are reasonable concerns in this regimen.     

葡萄胎恶变相关因素的探讨及瘦素在妊娠滋养细胞疾病中表达的临床意义

目的通过测定瘦素（LEP）在不同类型滋养细胞疾病中的表达,探讨其预测葡萄胎恶变和转移的可能性;并对葡萄胎恶变相关因素进行分析,以提高对葡萄胎预后的判断。方法应用过氧化物酶免疫组织化学方法对30例正常早孕（〈12周）绒毛组织、32例部分性葡萄胎、93例完全性葡萄胎、30例侵蚀性葡萄胎、5例绒毛膜癌组织中LEP进行检测。分析7例发生恶变的葡萄胎患者的发病年龄、子宫大小、卵巢黄素囊肿、血β-人绒毛膜促性腺激素（hCG）等斟素。结果LEP在正常早孕绒毛组织、部分性葡萄胎、完全性葡萄胎、侵蚀性葡萄胎、绒毛膜癌组织中均有表达,表达阳性率与病变程度呈正相关（X2=23．49,P〈0．05）。结论LEP与正常早孕滋养细胞的侵袭过程有关,LEP在滋养细胞疾病组织中表达的强度,与滋养细胞恶性程度的强度有关。对临床早期预测葡萄胎的恶变及预防性化疗有一定的参考意义。葡萄胎恶变还与患者发病年龄、B—hCG水平、子宫大小、卵巢黄素囊肿等因素有关。     

Perspectives in chemotherapy of advanced gastric cancer.

A review of recent phase II and III studies in advanced gastric carcinoma is presented. Several combination regimens have been developed with high activity in locally advanced and metastatic disease. Among them are etoposide plus adriamycin plus cisplatin (EAP), etoposide plus 5-fluorouracil plus leucovorin (ELF), continuous infusion 5-fluorouracil plus cisplatin and high dose methotrexate plus 5-fluorouracil plus adriamycin (FAMTX). In locally advanced disease a resectability rate of +/- 50% has been reported with these protocols. So far only FAMTX has demonstrated superiority compared with 5-fluorouracil, adriamycin and mitomycin (FAM), which regimen has been considered 'standard' treatment for many years. Randomized studies in which the other regimens are being more definitely assessed are underway.     

Clinical pharmacology confounders in older adults

The activity of chemotherapy as salvage therapy for recurrent bladder cancer has been well defined, although the optimum therapy combination is less clear. Since the early nineties several cisplatin based regimens have been compared but no one regimen has reported a superior benefit. Currently, regimens such as methotrexate, vinblastine, doxorubicin and cisplatin and gemcitabine-cisplatin should be considered two equal alternatives in patients eligible for cisplatin, but the differing toxicity profiles should be evaluated in the choice of treatment. The use of a triple combination with paclitaxel, gemcitabine and cisplatin should be avoided in clinical practice, although its use may be carefully considered in patients needing a rapid downsizing of disease and with primary bladder tumor. Despite this evidence, several questions remain, and there is a need for answers in the future.     

The chemotherapy of head and neck cancer

Studies of combination therapy [with agents such as cisplatin, 5-fluorouracil (5-FU) and methotrexate] have shown some improvements in response rate; however, no obvious survival advantage over monotherapy in the treatment of patients with metastatic or advanced locoregional cancer of the head and neck have been observed. In the neoadjuvant setting, chemotherapy is helpful in preserving the larynx and hypopharynx but has no proven impact (positive or negative) on survival. New treatment options are needed to improve survival in head and neck cancer. Among the new options for chemotherapy in metastatic/recurrent disease is docetaxel. With monotherapy, response rates of 23-42% are seen, and, when used in combination with cisplatin and 5-FU, response rates of 52-100% have been reported in phase I/II trials. A phase III trial of the addition of docetaxel to standard neoadjuvant therapy with cisplatin and 5-FU is now underway.     

环氧化酶-2和血管内皮细胞生长因子在妊娠滋养细胞肿瘤中的表达及意义

目的 探讨环氧化酶-2（COX-2）及血管内皮细胞生长因子（VEGF）对妊娠滋养细胞肿瘤发生发展及预后估计的作用.方法 采用免疫组化SABC法检测COX-2、VEGF在正常绒毛和妊娠滋养细胞疾病中的表达.结果 妊娠滋养细胞肿瘤组较正常绒毛及葡萄胎组COX-2、VEGF的表达率均明显增高（P＜0.01）;妊娠滋养细胞肿瘤中,COX-2与VEGF的表达呈正相关（r=0.795,P＜0.01）.结论 COX-2与VEGF的高表达协同积累可促使滋养细胞恶性转化,提示预后不良.     

Gemcitabine in the treatment of bladder cancer

New agents are available for the treatment of metastatic transitional cell carcinoma of the bladder. In the US, the combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) remains the standard chemotherapy regimen for advanced bladder cancer. Gemcitabine (2',2'-difluorodeoxycytidine [dFdC]) is a relatively new agent with a favourable toxicity profile that has demonstrated activity against a number of solid tumours in both preclinical and clinical studies. Single-agent gemcitabine has shown activity in bladder cancer in both pretreated and chemotherapy-na?ve patients. The combination of gemcitabine plus cisplatin is a regimen with significant activity and moderate toxicity in bladder cancer patients. A randomised trial of gemcitabine plus cisplatin versus M-VAC has completed accrual but has not yet been reported. New combination studies of gemcitabine with other chemotherapy agents, including the taxanes, are ongoing.     

Gemcitabine in the treatment of bladder cancer

New agents are available for the treatment of metastatic transitional cell carcinoma of the bladder. In the US, the combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) remains the standard chemotherapy regimen for advanced bladder cancer. Gemcitabine (2′,2′-difluorodeoxycytidine [dFdC]) is a relatively new agent with a favourable toxicity profile that has demonstrated activity against a number of solid tumours in both preclinical and clinical studies. Single-agent gemcitabine has shown activity in bladder cancer in both pretreated and chemotherapy-naïve patients. The combination of gemcitabine plus cisplatin is a regimen with significant activity and moderate toxicity in bladder cancer patients. A randomised trial of gemcitabine plus cisplatin versus M-VAC has completed accrual but has not yet been reported. New combination studies of gemcitabine with other chemotherapy agents, including the taxanes, are ongoing.     

Bendamustine

Bendamustine is a bifunctional alkylating agent with cytotoxic activity against human ovarian and breast cancers in vitro. It shows only partial in vitro cross-resistance with cyclophosphamide, melphalan, carmustine and cisplatin. Bendamustine as monotherapy or as part of combination chemotherapy protocols for first-line or subsequent treatment produced objective response rates of 61 to 97% in patients with Hodgkin's disease or non-Hodgkin's lymphoma (NHL) [41 to 48% in high grade NHL]. In patients with multiple myeloma, a bendamustine/prednisone regimen produced a higher rate of complete response (32 vs 11%) and more durable responses than a melphalan/prednisone regimen. Substitution of bendamustine for cyclophosphamide in a standard first-line COP regimen (cyclophosphamide, vincristine and prednisolone) yielded similar response rates in patients with advanced low grade NHL. Substituting bendamustine for cyclophosphamide in the CMF protocol (cyclophosphamide, methotrexate and fluorouracil) prolonged remission from 6.2 to 15.2 months in patients with metastatic breast cancer. The most common adverse events in patients receiving bendamustine are haematological events and gastrointestinal disturbances. Bendamustine has a relatively low propensity to induce alopecia.