Spinal metastases: treatment evaluation algorithm

Spinal metastases are only apparently similar lesions, considering the large varieties of istotypes and the spread of the primary tumor. These metastases develop early and are not terminal events, they have to be considered as severe complications because, when possible, surgical treatment can improve the history of the patient in terms of life expectancy and quality of life. The approach to these lesions should be multidisciplinary in collaboration with oncologists and radiotherapists, in fact the average of survival of these patients has increased in recent years. The evolution of anesthaesiological techniques that permit surgical treatments that were once considered prohibitive. The application of new adjuvant therapy increases the effectiveness for surgical treatment. Controversy exist over the most appropriate treatment for patients with metastatic disease of the vertebral column. The purpose of this article was to determine the best sequential process to arrive at the most appropriate treatment considering the individual general conditions and the parameters of the metastases. We review 269 cases in 182 patients suffering from spinal metastases from a solid tumour treated between 1996 and 2002. As the number of treatment options for metastatic spinal disease has grown, it has become clear that effective implementation of these treatments can only be achieved by multidisciplinary approach.     

不同剂量头孢呋辛辅助治疗AECOPD的临床效果观察

目的 探讨不同剂量头孢呋辛辅助治疗慢性阻塞性肺疾病急性加重期（AECOPD）的临床效果。方法 将80例AECOPD患者根据入院顺序分为治疗组与对照组,每组各40例,两组均给予序贯机械通气治疗,对照组辅助大剂量头孢呋辛治疗,治疗组辅助小剂量头孢呋辛治疗。结果 治疗后治疗组与对照组的总有效率分别为97．5％和95．0％,两组差异无统计学意义（P〉0．05）。治疗组的FEV1、FEV1／FVC与PEF值与对照组比较差异无统计学意义（P〉0．05）。治疗组口干、尿潴留等不良反应发生率明显低于对照组,差异有统计学意义（P〈0．05）。结论 小剂量头孢呋辛辅助治疗AECOPD,能在保持良好疗效的基础上降低不良反应发生率,值得推广应用。     

Current pharmacological treatment approaches to central nervous system leukaemia.

Significant advances in the treatment and prevention of meningeal leukaemia have been made in the past 3 decades. This progress has resulted from the development of innovative approaches to treatment as well as a better understanding of the pharmacokinetics and pharmacodynamics of the commonly used antileukaemic agents. Intrathecal therapy, via the intralumbar or intraventricular route, is a form of regional therapy that results in the delivery of very high drug concentrations to the principle target tumour site (the meninges) using a relatively small drug dose, thereby minimising both systemic drug exposure and systemic toxicity. The dosage and schedules, clinical pharmacology and toxicities of the commonly used intrathecal agents, methotrexate and cytarabine (cytosine arabinoside; Ara-C) are discussed in detail. Another approach which has been used to overcome the poor penetration of antileukaemic drugs into the CNS has been the use of high-dose systemic therapy. This strategy has been successfully applied in the treatment of meningeal leukaemia using both high-dose methotrexate and high-dose cytarabine. The clinical pharmacology, toxicities, and potential limitations of this approach are outlined. Finally, new agents that are currently undergoing clinical evaluation and future directions for research are also discussed.     

Recurrent and metastatic clivus chordoma: systemic palliative therapy retards disease progression

We report on a male patient with progressive and metastatic clivus chordoma treated over a period of 9 years by a multidisciplinary approach. Within the first 4 years, the patient underwent surgery four times. Thereafter, he received radiotherapy and subsequent chemotherapy. Stabilization of disease was achieved repeatedly for variable periods under local radiotherapy, systemic chemotherapy, immunomodulatory and anti-angiogenic therapy with isotretinoin and interferon-alpha, followed by thalidomide. Due to the occurrence of brain and lung metastases 8 years after initial diagnosis, liposomal doxorubicin was added to thalidomide. At the last follow-up control the patient had stable disease, with no progression of the intracranial tumor and regression of pulmonary metastases. He is in a good physical, psychological and neurological condition with a Karnofsky score of 80. Our observations show that multimodal therapy including a systemic palliative approach is associated with long quiescent intervals in recurrent chordoma and with regression of its metastases. Use of substances with high efficacy on tumor tissue and low toxicity, allowing long-term administration, seems promising in similar situations.     

Phase II study of miltefosine 6% solution as topical treatment of skin metastases in breast cancer patients

Topical treatment of skin metastases with a cytotoxic agent is attractive for its easy self-administration and absence of major systemic interference. Miltefosine exerts its cytotoxicity by acting on cell membrane phospholipids and can be administered topically. Twenty breast cancer patients with progression of skin metastases were treated with a 6% solution of miltefosine, which was topically administered once daily during the first week and twice daily thereafter. Sixteen out of 20 patients also had metastatic disease at other sites. Concomitant systemic treatment when ongoing for at least 2 months prior to study entry was permitted, and consisted of chemotherapy and hormonal therapy in seven and nine patients, respectively. Prior palliative cytotoxic and hormonal therapy had been administered to 11 and 19 patients, respectively. No grade 3 and 4 toxicity occurred. Miltefosine therapy was discontinued in two patients due to nausea and in one patient due to skin toxicity. Grade 1 and 2 adverse skin reactions, and nausea and vomiting were seen in 11 and two patients, respectively. In 18 patients evaluable for response, four partial responses were noted (response rate 22%), while seven patients had stable disease. Three partial responses were observed in patients in whom the skin lesions were smaller than 1.5 cm2. Median duration of response was 2.5 months and median time to progression for all patients was 1.9 months. In this study topically applied miltefosine for metastatic skin lesions of breast cancer showed modest activity in a relatively heavily pretreated patient population, without serious systemic toxicity.     

不同剂量盐酸氨溴索治疗慢性阻塞性肺疾病急性加重期老年患者的疗效比较

目的 研究不同剂量盐酸氨溴索治疗慢性阻塞性肺疾病急性加重期（AECOPD）老年患者的疗效.方法 选择在温岭市康复医院内科住院的AECOPD老年患者104例,根据住院顺序随机分为大剂量组和小剂量组,各52例.2组患者均接受吸氧、解痉、抗感染等常规治疗,大剂量组患者在此基础上静脉滴注盐酸氨溴索120 mg/d,小剂量组患者静脉滴注盐酸氨溴索60 mg/d.连续治疗1周后,观察2组患者的临床表现、血气等指标的改善情况.结果 大剂量组的总有效率为90.4％ （47/52）,小剂量组的总有效率71.2％ （37/52）,组间差异有统计学意义（P＜0.05）.治疗后2组患者的氧分压和二氧化碳分压相比较,大剂量组指标明显优于小剂量组[（65.2±2.7） mmHg（1 mmHg=0.133 kPa）比（60.9±2.2） mmHg,（46.2±3.0） mmHg比（50.1 ±2.7）mmHg],差值差异有统计学意义[（11.7±1.9） mmHg比（10.5±1.6） mmHg,（12.57±0.22） mmHg比（12.15 ±2.67）mmHg] （P ＜0.05）.结论 大剂量盐酸氨溴索的临床疗效显著,可明显改善患者的症状.     

肝癌肝移植术后肺部转移瘤的治疗

目的研究不同方案对肝癌肝移植术后肺部转移瘤的治疗效果。方法肝癌肝移植术后肺部转移瘤患者19例,A组14例索拉非尼联合消癌平口服。液治疗,B组5例放射治疗。结果A组随访5～33个月,2例患者分别于治疗第5、7个月死亡,1例患者治疗6个月转移瘤消失,2例患者治疗第3、4个月转移瘤逐步减小,9例患者良好带瘤生存索拉非尼半量治疗者,2例生存超过20月,5例超过12个月;B组患者6个月内死亡3例,余2例肿瘤进展明显。两组间总体生存率分别为85．7％、40．0％,有显著统计学差异（P=0．022）。结论肝癌肝移植术后复发者肺部转移瘤常见。索拉非尼联合消癌平口服液治疗肝移植术后肺部转移瘤疗效确切,显著延长生存时间,半量治疗者联合消癌平口服液也能取得良好的疗效;放射治疗肝移植术后肺部转移瘤效果不佳。     

Low-dose weekly oral methotrexate therapy for inflammatory arthritis

The efficacy and toxicity of low-dose, weekly oral methotrexate (MTX) therapy for inflammatory arthritis was evaluated. Fifty-nine patients with a diagnosis of inflammatory arthritis who had failed to respond to or developed toxicity to gold, penicillamine, or hydroxychloroquine therapy were treated with MTX 10-20 mg administered orally or intravenously once a week in divided doses. Various tests to assess arthritis were performed upon each patient's entrance into the study and at specified intervals throughout the 24-month study period. The mean duration of methotrexate therapy was 15.5 months. Patients showed significant improvement in number of swollen joints, duration of morning stiffness, amount of pain, and amount of activity during the study period. Of the 35 patients who had had roentgenographic studies of their hands performed initially and after one year of MTX therapy, 23 had no evidence of new joint erosions after one year. Biopsies of hepatic tissue from 20 patients showed no progressive changes when compared with pretreatment biopsies. Gastrointestinal symptoms, mucocutaneous lesions, or small increases in liver enzyme concentrations were observed in 31 patients; three patients developed pulmonary toxicity and had to be withdrawn from the study. MTX is an effective agent for the treatment of inflammatory arthritis in patients who do not respond to therapy with nonsteroidal anti-inflammatory drugs or slow-acting antirheumatic drugs. Short-term weekly oral MTX therapy does not appear to result in clinically important liver disease.     

多学科合作模式对老年中重度慢性阻塞性肺疾病患者康复作用的研究

目的 探讨多学科合作模式对老年中、重度慢性阻塞性肺疾病（COPD）的康复效果.方法 将80例老年中、重度COPD住院患者分为2组,多学科合作呼吸康复组（治疗组）45例,对照组35例.2组均采用常规临床治疗,治疗组在常规临床治疗基础上加用多学科合作综合康复措施,疗程均为3个月.比较治疗前、后2组BODE指数及生活质量指数.结果 治疗30、60 d后,治疗组6 min步行距离（6-MWT）、BMI、呼吸困难修正评分（MMRC）、BODE指数及圣乔治呼吸问卷总分与对照组同一时间相比,差异均有统计学意义（P＜0.05）;治疗90 d后,治疗组上述各项指标与对照组相比[（463.0±35.1）m比（311.0±33.7）m,（22.0±4.1）kg/m2比（20.0±3.8）kg/m2,（2.0±0.8）分比（3.0±0.9）分,（3.0±1. 0）分比（7.6±0.9）分,（40.6±7.5）分比（52.8±4.8）分],差异均有统计学意义（均P＜0.01）.对照组治疗30、60、90 d后的6-MWT与治疗前相比,差异亦有统计学意义（P＜0.05）.结论 采用多学科合作模式对老年中、重度COPD患者进行呼吸康复训练,能明显降低患者的BODE指数,改善COPD患者的呼吸困难症状,提高患者生存质量.     

Response of metastatic adenoid cystic carcinoma and Merkel cell tumor to high-dose Melphalan with autologous bone marrow transplantation

Summary Two patients with metastatic spread of unusual tumors responded to treatment with high-dose Melphalan and autologous bone marrow transplant. One patient had adenoid cystic carcinoma of a minor salivary gland and the other had Merkel cell tumor of the scalp. Both patients had undergone prior surgery and radiotherapy, but later relapsed with distant metastases. Both patients had progression of their disease despite conventional and salvage chemotherapy. Treatment with high-dose Melphalan and autologous bone marrow transplant resulted in partial responses for both patients. High-dose Melphalan should be considered for therapy earlier in the course of patients with these unusual cancers.     

舒利迭治疗中、重度慢性阻塞性肺病疗效评价

目的：观察舒利迭（50/500μg）在慢性阻塞性肺病（COPD）缓解期中的疗效。方法：确诊的中、重度COPD患者40例,随机分为对照组和治疗组。对照组给予解痉平喘、祛痰等基础治疗;治疗组在此基础上给予舒利迭50/500μg,每次1吸,每日2次。分别对两组患者治疗前后的临床症状及肺功能指标进行观察对比,评价药物疗效。结果：治疗组患者治疗前后FEV1、FEV1/FVC×100%、FEV1%预计值差异具有统计学意义（P〈0.05）,而对照组治疗前后各指标差异无统计学意义。结论：在中、重度COPD患者中应用舒利迭能提高患者肺功能,明显改善症状,提高生活质量。     

Potentially Serious Drug Interactions Secondary to High-Dose Diltiazem Used in the Treatment of Pulmonary Hypertension

Two patients had potentially serious drug interactions (phenytoin, digoxin) that were probably attributable to changes in pharmacokinetics and pharmacodynamics caused by high-dose calcium channel blocker therapy (diltiazem) in the treatment of pulmonary hypertension. Even in the approved normal dosages for the treatment of angina and hypertension, calcium channel blockers are known to cause significant changes in the metabolism of other drugs. Currently, no data exist on the effects of the very high dosages of these drugs, administered to patients with pulmonary hypertension, on the metabolism and clearance of other agents, although, based on our experience and literature reports, recommendations for monitoring therapy can be made.     

Treatments for improving survival of patients with prostate cancer

Prostate cancer is a heterogeneous disease characterised by a long natural history relative to other solid tumours. With the diagnosis of prostate cancer being made earlier, the emphasis of treatment has shifted from palliation of symptoms to altering disease-related morbidity and mortality and thus improving overall survival. Treatment of prostate cancer increasingly involves an approach that combines local therapies directed at the primary tumour together with systemic therapies to potentiate their effect and to control subclinical metastatic disease. Patients with localised tumours who are at high risk of relapsing with radiation therapy alone are surviving longer because of the addition of adjuvant hormonal therapy. Although a survival benefit in similar patients undergoing prostatectomy has not yet been established, preliminary results indicate that adjuvant hormonal therapy delays relapse. Chemotherapy is an effective palliative modality for patients with hormone- refractory metastatic disease, and recently completed phase III trials will determine if chemotherapy can prolong survival for this group. The role of chemotherapy in patients with locally advanced tumours is also being investigated in randomised clinical trials. Because bone is the dominant site of metastases for most patients with prostate cancer, the development of therapies that can slow tumour growth specifically within bone is a logical strategy. Bisphosphonates and bone-targeted radionuclides are two such approaches that have shown encouraging results even in the most advanced stages of the disease. Although one can now reasonably hypothesise that survival has improved because of recent therapeutic advances, it remains to be conclusively established that cytotoxic or other systemic therapy can extend survival of patients with prostate cancer. Only the results of ongoing randomised trials can definitely establish that more patients with locally advanced and metastatic prostate cancer are living longer.     

家庭氧疗对慢性阻塞性肺疾病的影响研究

目的探讨家庭氧疗对慢性阻塞性肺疾病的影响。方法将120例慢性阻塞性肺部疾病患者分为治疗组与对照组各60例,两组首先均采用常规药物控制方法,治疗组在此基础上加用积极的家庭氧疗。结果经过治疗后,治疗组临床效果（100.0%）明显优于对照组（80.0%）,两组数据在统计学上差异有统计学意义（P〈0.05）。治疗组和对照组患者治疗前VT、FEV1、FVC比较差异无统计学意义。治疗组患者治疗8周后FEV1与治疗前比较明显增加（P〈0.05）。其他指标两组对比以及与治疗前对比差异均无统计学意义。结论家庭氧疗能够提高慢性阻塞性肺疾病的治疗效果,改善肺功能,值得推广应用。     

Comparison of intravenous and oral high-dose methotrexate in treatment of solid tumours.

An outpatient regimen of oral high-dose methotrexate was studied in 14 patients with solid tumours over 12 months. Detailed pharmacokinetic analysis in five patients showed high oral bioavailability (mean +/- SE of mean 87.6 +/- 1.5%), indicating that with this regimen oral methotrexate was well absorbed and the first-pass effect low. Oral administration resulted in peak plasma methotrexate concentrations of 8.4 +/- 0.5 mumol/l (382 +/- 23 microgram/100 ml) and was almost as effective as intravenous administration, which achieved peak concentrations of 9.9 +/- 0.4 mumol/l (450 +/- 18 microgram/100 ml). In all 14 patients the clinical response to oral treatment was comparable to that reported to intravenous administration of high-dose methotrexate used in combination with other cytotoxic drugs. The disease-free interval in cases of adult sarcoma was 7.4 +/- 1.3 months and the relapse rate 29%. Out of four patients with small-cell carcinoma, two showed an objective response to oral treatment. We suggest that oral high-dose methotrexate given in divided doses is a rational alternative to expensive intravenous high-dose methotrexate regimens, but further clinical evaluation is necessary.     

Fistula response to methotrexate in Crohn's disease: a case series

BACKGROUND: Controlled trials have demonstrated the efficacy of methotrexate in the induction and maintenance of remission in luminal Crohn's disease; however, its effect on fistulizing disease is unknown. AIM: To describe the response to methotrexate therapy in a series of patients with fistulizing Crohn's disease. METHODS: A retrospective chart review was conducted of all patients with Crohn's disease receiving methotrexate in one practice. The response of patients with fistulizing and luminal disease was assessed using clinical and laboratory criteria. Fistula response was categorized as either complete or partial closure. RESULTS: Thirty-seven courses of methotrexate therapy were given to 33 patients with luminal and/or fistulizing Crohn's disease. In 16 patients with fistulas, four (25%) had complete closure, five (31%) had partial closure and all had failed or were intolerant to 6-mercaptopurine therapy. Overall, response to methotrexate was seen in 23 of 37 (62%) treatment courses in patients with luminal and/or fistulizing Crohn's disease. Two of the 33 patients (6%) had a significant adverse event. CONCLUSIONS: In this case series, 56% of patients with Crohn's fistulas on methotrexate showed a complete or partial response to therapy. Further studies are needed to confirm the role of methotrexate alone, and in combination with other therapies, for the treatment of fistulizing Crohn's disease.     

雾化吸入硝酸甘油对慢性肺心病血流动力学的影响

目的 观察雾化吸入硝酸甘油对慢性肺心病血流动力学的影响.方法 将60例符合条件的慢性肺心病住院患者随机分为治疗组和对照组.对照组给予常规治疗,治疗组在常规治疗的基础上加用雾化吸入硝酸甘油,3d后观察二组的临床疗效.结果 治疗组显效率73.3%,总有效率为90.0%;对照组显效率为46.7%,总有效率为67.2%,治疗后二组疗效对比,显效率和总有效率差异均有统计学意义(P＜.05).雾化吸入硝酸甘油10 min、60 mim、1 d、2 d和3 d右室射血前期(RPEP)/加速时间(AT)、肺动脉平均压(PAMP)均较吸入前基础值明显下降(P＜.05).而HR、平均动脉压(MAP)、肺动脉峰值血流速度(PA)及雾化吸入硝酸甘油后与吸入前基础值相比均无明显变化(P＜0..05).结论 雾化吸入硝酸甘油可以降低慢性肺心病肺动脉高压,改善肺动脉高压患者肺循环的血流动力学,而对体循环无明显影响.     

Resumption of high-dose methotrexate after methotrexate-induced nephrotoxicity and carboxypeptidase G2 use.

PURPOSE: The successful resumption of high-dose methotrexate in a 13-year-old boy with recurrent anaplastic large-cell lymphoma (ALCL) who suffered renal dysfunction after a 24-hour infusion of high-dose methotrexate and required treatment with carboxypeptidase G(2) (CPDG(2) ) is described. SUMMARY: A 13-year-old boy who had been diagnosed in 2001 with stage I ALCL was admitted to the hospital in February 2005 after he developed a smaller left axillary mass in the area of his original mass. Recurrent ALCL was diagnosed, and treatments were initiated based on branch K3 of the protocol published in the non-Hodgkin's lymphoma-Berlin-Frankfurt-Münster (NHL-BFM) trial 90. In the NHL-BFM 90 protocol, all AA and BB courses include high-dose methotrexate therapy, which consists of aggressive alkalinized hydration, methotrexate 5 g/m(2) given as an i.v. infusion over 24 hours, and leucovorin rescue. During course BB2, the boy's serum methotrexate values exceeded NHL-BFM goals at 36, 42, and 48 hours. Because the patient's elimination of methotrexate remained slow and his serum creatinine level remained above normal limits, CPDG(2) was obtained for the treatment of methotrexate toxicity. The patient tolerated the CPDG(2) without adverse effects, and the patient's serum methotrexate concentration decreased from 14.47 to 0.66 microM. The patient went on to complete six courses based on the protocol. High-dose methotrexate was resumed at 50% then 100% of the original dose. He is currently in remission on maintenance therapy. CONCLUSION: A 13-year-old boy with recurrent ALCL had methotrexate-induced nephrotoxicity following high-dose methotrexate. The resultant delayed methotrexate clearance required the standard therapies as well as use of investigational CPDG(2). High-dose methotrexate was successfully resumed.     

Optimal treatment of Zollinger-Ellison syndrome and related conditions in elderly patients

Zollinger-Ellison syndrome is characterised by refractory peptic ulcer disease, severe diarrhoea and gastric acid hypersecretion associated with an islet-cell tumour of the pancreas (gastrinoma). The true incidence and prevalence of this rare disease is unknown; in the US, the frequency is one per one million people and the age at presentation varies from 7 to 90 years. Zollinger-Ellison syndrome is sporadic in 62-80% of cases and in 20-38% of cases is associated with multiple endocrine neoplasia type 1 (MEN 1). The diagnosis of Zollinger-Ellison syndrome is certain when the plasma gastrin is >1000 pg/mL and the basal acid output is >15 mEq/h in patients with an intact stomach, >5 mEq/h in gastrectomised patients, or when this hypergastrinemia is associated with a pH <2. The treatment is based on control of gastric acid hypersecretion and of the malignant tumour and its possible metastases.Proton pump inhibitors are the most effective antisecretory drugs and can be administered in the elderly at high dosages without drug-related adverse effects. As an initial therapy, daily dosages of omeprazole 80-100 mg or pantoprazole 40-160 mg are employed. In long-term treatment the doses can be greatly reduced once effective control of the gastric output has been established. Intravenous proton pump inhibitors may be administered when patients cannot take oral therapy, particularly in acute conditions. All sporadic localised gastrinomas should be excised if possible. When liver metastases are also present, their debulking may improve symptoms and survival, and facilitate medical treatment. There is some controversy as to the surgical approach for gastrinomas associated with MEN 1.Somatostatin analogues can be useful in reducing gastric acid hypersecretion, serum gastrin and gastric enterochromaffin-like (ECL) cells and can thus contribute to treating the disease more effectively. Their antiproliferative effect can be used in treating liver metastases. Chemotherapy is not the therapy of choice in patients with gastrinomas and is indicated only in those with malignant progressive disease; interferon alpha, embolisation and chemoembolisation are not advisable for the elderly.The treatment of elderly Zollinger-Ellison syndrome patients, similarly to all elderly oncological patients, should be based on the use of comprehensive geriatric assessment. This will enable the clinician to define the functional status of the elderly person, to decide whether the patient can tolerate surgery and/or the stress of antineoplastic therapy, and finally, to determine whether this patient can tolerate an aggressive treatment for Zollinger-Ellison syndrome or whether the only possible choice is palliative relief of symptoms.     

不同疗程糖皮质激素治疗慢性阻塞性肺疾病急性加重期的疗效观察

目的观察不同疗程糖皮质激素治疗慢性阻塞性肺疾病急性加重期的临床效果。方法将86例慢性阻塞性肺疾病急性加重期患者随机分为观察组和对照组各43例。2组均采用全身应用糖皮质激素治疗,观察组采用5d疗法,对照组采用14d疗法。观察2组临床疗效、血气分析、肺功能及不良反应情况。结果2组临床疗效、血气指标、肺功能改善情况差异均无统计学意义（P〉0．05）;观察组不良反应发生率低于对照组,差异有统计学意义（P〈0．05）。结论糖皮质激素治疗慢性阻塞性肺疾病急性加重期效果显著,而5d短期疗法能有效减少患者的不良反应,值得临床推广应用。