超大剂量盐酸羟考酮缓释片与硫酸吗啡缓释片治疗重度癌痛的疗效及安全性比较

目的:观察超大剂量盐酸羟考酮缓释片(奥施康定)与硫酸吗啡缓释片(美施康定)治疗重度疼痛的临床疗效及安全性.方法:将重度疼痛的晚期肿瘤患者随机分为盐酸羟考酮缓释片组(奥施康定组)和硫酸吗啡缓释片(美施康定组)组,剔除观察期内(14天)两组患者中奥施康定和美施康定使用未达到超大剂量的患者.共有76例患者纳入本研究,其中奥施康定组33例,美施康定组43例.比较两组患者的止痛疗效、生活质量、不良反应.结果:奥施康定组达到首次疼痛控制稳定时间短于美施康定组,且在观察期间内,奥施康定组爆发痛发生次数以及解救药物使用剂量均少于美施康定组,差异具有统计学意义(P<0.05).奥施康定组疼痛缓解率87.88%,美施康定组疼痛缓解率83.72%,两组相比差异无统计学意义(P>0.05).奥施康定组和美施康定组治疗后生活质量较治疗前好转,差异有统计学意义(P<0.05);两组患者用药后生活质量变化比较,差异无统计学意义(P>0.05).治疗过程中,奥施康定组便秘发生情况低于美施康定组,差异具有统计学意义(P<0.05).结论:奥施康定和美施康定可有效缓解晚期癌症患者的疼痛,改善患者生活质量,具有较好的临床疗效,但盐酸羟考酮缓释片止痛快速、持久、稳定,不良反应发生率低.     

盐酸羟考酮控释片治疗中重度癌痛疗效观察

目的:观察盐酸羟考酮控释片(奥施康定oxycontin)对中重度癌性疼痛的镇痛效果和不良反应。方法:60例中重度癌痛患者随机分为两组:羟考酮组及对照组硫酸吗啡控释片(美施康定MS-contin)组各30例。羟考酮起始剂量10mg/12h,根据疼痛缓解程度调整剂量。评价镇痛效果、生活质量及不良反应。结果:羟考酮组患者疼痛程度显著减轻,总有效率96.1%。患者治疗后生活质量明显改善(P<0.01)。不良反应主要为便秘、头晕、恶心、呕吐、嗜睡等,无严重不良反应发生。对呼吸、血压、心率及肝肾功能无明显影响。结论:羟考酮控释片治疗中重度癌痛镇痛效果与对照组美施康定相近,起效快,副反应轻,服用安全,是中重度癌痛治疗的首选药物之一。     

盐酸羟考酮控释片与美沙酮治疗重度癌痛的临床疗效比较

目的探讨不同剂量盐酸羟考酮控释片(奥施康定)转换成美沙酮治疗重度癌痛的疗效、不良反应及药物价格。方法 25例口服奥施康定治疗重度癌痛患者按不同比例转换成美沙酮口服治疗,分别记录药物使用剂量、疼痛缓解率及不良反应、生活质量、药物费用、药物优势等。结果25例口服奥施康定患者的疼痛缓解率为88.0%,转换为口服美沙酮后,患者的疼痛缓解率为96.0%。美沙酮的周用量药物价格中位数为180.4元,明显低于奥施康定中位数501.4元,差异有统计学意义(t=3.1,P<0.01)。奥施康定治疗时,患者的恶心、呕吐和便秘更多见,与美沙酮治疗相比,差异均有统计学意义(P<0.01);美沙酮治疗时头,患者的晕和嗜睡更多见,与奥施康定治疗相比,差异有统计学意义(χ2值分别为7.0、12.8,P<0.01);药物优势评定显示更多患者喜欢使用美沙酮治疗,差异有统计学意义(P<0.01)。结论美沙酮和奥施康定均可有效控制重度癌痛,安全性好。在奥施康定药物治疗效果不佳或剂量大时可考虑转换美沙酮治疗,而且美沙酮剂量小、经济,不良反应也较少,更多患者愿用美沙酮进行治疗。     

奥施康定联合静脉注射吗啡治疗癌痛及爆发痛的临床研究

目的 研究奥施康定联合静脉注射盐酸吗啡注射液在癌痛及其爆发痛的初始治疗阶段的疗效。方法 回顾我科2011年1月—2015年11月住院治疗的中重度癌痛患者78例,阿片类药物的剂量滴定应用奥施康定作为背景阿片药物,联合静脉注射吗啡治疗爆发痛,对疗效及药物应用的情况进行分析。结果 在疼痛滴定或再次滴定的前5天内累计每个患者应用阿片类药物的等效剂量(MED)为156~1 491 mg(426.46±286.00 mg),爆发痛解救应用的吗啡注射液剂量为2~57 mg(20.96±13.25 mg);夜间(20时~次日8时)爆发痛解救应用吗啡注射液人均剂量为2.23±2.50 mg,高于白天(8时~20时)剂量1.96±2.14 mg(P＜0.05),治疗后NRS评分与治疗前比较均明显降低,治疗前后对比均具有统计学差异(P＜0.05)。结论 奥施康定联合静脉注射吗啡治疗中重度癌痛及爆发痛是一种安全高效、简单易行的方法,显著改善患者的生活质量,是中重度癌痛滴定治疗阶段的首选方案。     

盐酸羟考酮缓释片联合即释吗啡片用于中重度癌痛患者滴定的疗效

目的:探讨盐酸羟考酮缓释片联合即释吗啡片用于中重度癌痛患者滴定的有效性和安全性。方法:采用数字分级法对疼痛进行评分,对中重度癌痛患者分别使用盐酸羟考酮缓释片10mg和20mg,q12h进行滴定,即释吗啡片10mg处理爆发痛,根据患者疼痛情况调整24h和48h盐酸羟考酮缓释片剂量,记录疼痛的缓解程度和不良反应。结果:85例患者中,通过盐酸羟考酮缓释片联合即释吗啡片滴定后,1h、24h、48h疼痛明显缓解率分别为62.4%、88.2%和100%,不良反应以消化道症状为主,表现为轻中度恶心（22.4%）、呕吐（15.3%）和便秘（38.8%）,均可控制,无尿潴留以及呼吸抑制发生。结论:盐酸羟考酮缓释片联合即释吗啡片对中重度癌痛患者的滴定方式快速、有效、安全及便利。     

四种阿片类镇痛药用于癌性疼痛治疗的药物经济学评价

目的:探讨盐酸吗啡缓释片(美菲康)、硫酸吗啡缓释片(美施康定)、盐酸羟考酮控释片(奥施康定)、芬太尼透皮贴剂(多瑞吉)用于癌性疼痛患者镇痛治疗的成本效果,为临床合理用药提供指导。方法:随机调查2011年2月至2012年4月我院240例分别使用美菲康(58例)、美施康定(60例)、奥施康定(62例)和多瑞吉(60例)治疗晚期癌痛的住院患者。美菲康给药初始剂量为30mg,q12h,美施康定给药初始剂量为30mg,q12h,奥施康定给药初始剂量为10mg,q12h,多瑞吉外用贴于皮肤,起始剂量4.2mg,q72h,治疗中出现暴发痛者给予硫酸吗啡即释片,根据疼痛缓解情况决定剂量的调整直至将疼痛缓解至病人满意的程度即VAS 0-3分。不良反应给予对症处理。比较用药一个月后的镇痛疗效、不良反应及用药成本,运用药物经济学成本-效果分析法评价四组治疗方案。结果:美菲康、美施康定、奥施康定和多瑞吉的疼痛缓解率分别为91.38%、91.67%、93.55%、93.33%,四组无显著性差异(P>0.05)。人均成本分别为1279.26元、1346.53元、1507.66元、2018.12元,成本-效果比分别为13.40、14.68、16.12、21.62。结论:美菲康、美施康定、奥施康定和多瑞吉用于晚期癌痛患者镇痛疗效相当,从药物经济学角度来看,美菲康是癌痛患者镇痛治疗的较佳选择。     

奥施康定治疗中重度癌痛临床观察

目的:观察盐酸羟考酮控释片(奥施康定)治疗中重度癌痛的疗效及不良反应.方法:采用开放试验方法,对49例中重度癌痛患者进行治疗.奥施康定起始剂量10mg/12h,根据疼痛缓解程度调整剂量,评价镇痛效果、KPS评分及不良反应.结果:49例中重度癌痛患者,平均镇痛时间12.45h.总有效率89.80%,中度疼痛组有效率93.75%,重度疼痛组有效率87.88%.KPS评分:28例(57.14%)升高,19例(38.78%)稳定,2例(4.08%)病情恶化死亡.不良反应主要为便秘7例(14.29%).结论:奥施康定治疗中重度癌痛疗效确切,不良反应轻,服用安全.     

盐酸吗啡剂量滴定在中重度癌痛治疗中的应用

目的：观察盐酸吗啡剂量滴定方法治疗中重度癌痛的疗效及毒副反应。方法对52例中重度癌痛患者进行盐酸吗啡剂量滴定，按NRS法每小时对患者疼痛进行评分，记录结果，并处理毒副反应，调整盐酸吗啡剂量，24 h后，将所用盐酸吗啡片总量换算成等量的硫酸吗啡缓释片，进行维持治疗。结果52例患者经盐酸吗啡片剂量调整后，疼痛均得到控制，滴定成功所需的时间在3-24 h，中位时间6 h，其中完全缓解40例（76.92%），明显缓解12例（23.08%）。毒副反应发生率低，且程度轻。结论盐酸吗啡片起效所需剂量个体差异很大，但疗效确切；毒副反应少且轻，容易处理，是基层医院首选的滴定药物之一。     

盐酸羟考酮缓释片与曲马多缓释片治疗中度癌痛的近期疗效比较

目的比较盐酸羟考酮缓释片（奥施康定）与曲马多缓释片（奇曼丁）治疗中度癌痛的近期疗效。方法将100例伴有中度癌痛患者随机分为奥施康定组和奇曼丁组,每组50例,分别接受奥施康定和奇曼丁的治疗。结果奥施康定组治疗后第3、7、10天的NRS评分均较奇曼丁组低,且奥施康定组治疗后第3天NRS评分下降幅度较奇曼丁组明显（P〈0.05）;奥施康定组的CR率和有效率分别为34.0%和100.0%,明显高于奇曼丁组的10.0%和84.0%（P〈0.05）;2组毒副反应发生率比较差异均无统计学意义（P〉0.05）。结论与奇曼丁相比,应用奥施康定治疗中度癌痛患者,能更快更有效缓解疼痛,而未增加毒副反应。     

盐酸羟考酮缓释片简化滴定法滴定和治疗中重度癌痛的有效性和安全性观察

目的：观察盐酸羟考酮缓释片简化滴定法滴定治疗中重度癌痛的临床疗效及安全性，为癌痛患者合理用药提供参考。方法：将我院胸部肿瘤科2017年5月20日至2019年7月20日收治的中重度癌性疼痛患者125例，采用盐酸羟考酮缓释片简化滴定法进行剂量滴定。观察用药后1h、12h、24h疼痛缓解率、前3日滴定完成率及1周后患者疼痛数字分级评分、疼痛缓解率、体力状况评分、生活质量评分及不良反应等。结果：125例中重度癌痛患者使用盐酸羟考酮缓释片后1h、12h、24h疼痛缓解率分别为61.6%、74.4%、88.8%，前1日、2日、3日滴定完成率分别为88.8%、93.6%、96.0%；治疗前、治疗1周后疼痛评分为4.15±1.71、1.39±0.84，差异有统计学意义 (P＜0.01)，疼痛总缓解率为98.4%；治疗1周后患者体力状况、生活质量评分均较治疗前增加 (P＜0.01)；不良反应发生率为84.0%。结论：采用盐酸羟考酮缓释片简化滴定法进行中重度癌痛的滴定和治疗能达到快速成功滴定并有效镇痛，治疗后患者的体力状况及生活质量明显改善，不良反应轻微，可作为临床上滴定和治疗中重度癌痛的优选方式。      

Experience in the treatment of synchronous and metachronous carcinoma of the oesophagus and the head and neck

BACKGROUND AND OBJECTIVES: Treatment of multiple primary squamous cell carcinomas of the head and neck and oesophagus is controversial. The poor prognosis of these 2 types of carcinoma taken individually and their anatomic proximity complicate the therapeutic strategy and limit the treatment choices for each location. METHODS: From 1986 to 1998, 43 patients received curative treatment for multiple synchronous (n = 30) or metachronous (n = 13) primary neoplasms of the oesophagus and head and neck. For synchronous cancers, the therapeutic strategy consisted of first curing the head and neck cancer and then planning oesophagectomy according to the type of head and neck cancer therapy. RESULTS: Ten total oesopharyngolaryngectomies and 33 subtotal oesophagectomies were performed. The postoperative mortality rate was 9.3% (4/43). The rate of anastomotic leakage was 30% (13/43), and all such leaks were cervical. Pulmonary infection occurred in 19% of cases (8/43). A past history of cervical radiation therapy or cervicotomy did not appear to be a significant risk factor for anastomotic leakage or pulmonary complications. Oesophagectomy did not affect the functional results in the 31 patients whose larynx could be preserved. CONCLUSIONS: Oesophagectomy after head and neck cancer treatment is possible with a low mortality rate and acceptable morbidity.     

Clinicopathological study of carcinomas of the lip and the mucosa of the upper and lower lips

BACKGROUND: Lip carcinomas are rare oral tumors, and there have been few reports of lip carcinoma in Japan. METHODS: Of 914 patients with oral carcinomas treated between January 1980 and December 1998, 12 (1.3%) had lip carcinoma and 5 (0.5%) had lip mucosal carcinoma. We investigated the clinicopathological features of these 17 patients. RESULTS: Of the 12 patients with carcinoma of the lip, 10 had squamous cell carcinomas (9, external lower lip; 1 commissures) and 2 had mucoepidermoid carcinomas (external upper lip). Of the 5 patients with lip mucosal carcinoma, 3 had squamous cell carcinomas (2, mucosa of the lower lip; 1, mucosa of the upper lip), 1 had mucoepidermoid carcinoma (mucosa of the lower lip), and 1 had acinic cell carcinoma (mucosa of the lower lip). Of the 12 patients with lip carcinoma, 9 were classified as stage I, 2 as stage II, and 1 as stage III; all 5 of the patients with lip mucosal carcinoma were stage I. Five patients with lip carcinoma were treated by resection, 5 by a combination of resection and reconstruction, and 2 by radiotherapy alone. All patients with lip mucosal carcinoma were treated by resection. After the initial therapy, 3 patients without neck dissection had regional recurrences and received delayed neck dissection, and 2 died with neck regional recurrence after dissection. The 5-year cumulative survival rates of the patients with lip carcinoma and those with lip mucosal carcinoma were 82.5% and 80.0%, respectively. CONCLUSION: We suggest that early-stage carcinomas of the lip and of the mucosa of the upper and lower lips are frequent, and we found that the outcome of these patients was excellent. However, an aggressive therapeutic approach to the lip carcinoma patient with cervical metastasis appears warranted, in an attempt to improve locoregional control and ultimate survival.     

The relation between the aging of the steroid generating system and the geneses of cancers of the stomach, the breast and the uterine cervix

The purpose of the present study is to test the validity of the steroid carcinogenesis hypothesis in humans by investigating the problem whether or not a cancer-specific change of the hormonal milieu emerges at a specified stage of life where the growth rate of cancer risk is at its zenith. A case-control study of 14 urinary steroid excretions was conducted for each of 3 human neoplasias. The identification and the size (in parenthesis) of the population units used in this study were,given as follows: a) the male gastric cancer group (421); b) the male control group (104); c) the female breast cancer group (245); d) the cervical cancer group (345); e) the female control group (127). Two kinds of steroid parameters were employed for the statistical analysis of hormonal data: a) the logarithm of a steroid excretion figure (mu g/day), as expressed by log x; b) the logarithm of a relative weight of a given steroid to tetrahydrocortisol, as expressed by log x/THF. The case-control difference for each parameter was expressed in terms of a t-value of Student's t-test. The steroid deviation profile was prepared for each neoplasia and for each of the log x data set and the log x/THF data set. The results obtained are as follows: a) the 2 steroid parameters (log x and log x/THF) for each of 14 urinary steroids were both subject to change with the progress of host age. The rate of age-dependent change was different for each steroid parameter and for each population unit. b) The above differential age dependency of the steroid parameters gave rise to a continual transition of the steroid deviation profile in the course of aging. c) The hormonal traits of male gastric cancer, female breast cancer and cervical cancer were described each as a complex of androgen depression and glucocorticoid stimulation (male gastric cancer), a sequential emergence of premenopausal progestin depression and postmenopausal predominance of glucocorticoid over androgen (female breast cancer), and a complex of androgen-glucocorticoid depression over progestin (cervical cancer). d) The emergence of the above cancer-specific steroid disorders chronologically coincided with the quasiexponential growth phase of cancer risk (and slow growth phase of cancer risk in postmenopausal breast cancer). e) The usefulness of the log x/THF type deviation profile for the assessment of the hormonal milieu of the host was verified by both theoretical approach to the problem and its application to the real data of a case-control study. f) The age dependent decline of androgens was generally much faster in their progressions than that of glucocorticoids - a finding to suggest the possibility that the production of a cancer-specific steroid deviation profile might have taken the form of the stress shift of Hans Selye, since both phenomena share depletion of gonadal steroids relative to glucocorticoid in common. The etiological relevancy of the 3 cancer-specific steroid changes to the geneses of 3 cancers:was discussed in the light of the experimental pathology studies in our laboratory as well as in other laboratories.     

Degree of manifestation of therapeutic pathomorphosis and the nature of the change in the estrogen and progesterone receptors after the radiation and chemotherapy of breast cancer

Estradiol and progesterone receptor levels were measured in 130 patients with stage III breast tumors before treatment and following preoperative radiation or chemotherapy. The data were evaluated versus the morphologic features of posttreatment pathomorphosis of tumor. Standard fractionated radiation (total dose of 70 Gy) was followed by pronounced postradiation pathomorphosis and a decrease in the level and incidence of steroid receptors in 72.7-87.5%. The essentially unchanged receptor profile of tumor following large-fraction (total dose-20 Gy) irradiation as well as presence of estradiol and progesterone receptors in the originally receptor-negative neoplasms after chemotherapy were matched by a slight degree of pathomorphosis.     

Effect of freezing the helix and the rim or edge of the human and pig ear

We have studied the effect of increasing freeze times on the normal pig's ear and on a variety of lesions of the human ear. The clinical and laboratory data suggest that cartilage necrosis secondary to cryosurgery is a dose-related phenomenon and is uncommon with the freeze times used in clinical practice. Cryosurgery is an effective and cosmetically acceptable treatment for superficial skin lesions of the ear.     

Patient-reported outcomes: Assessment and current perspectives of the guidelines of the Food and Drug Administration and the reflection paper of the European Medicines Agency

AimsPatient-reported outcomes (PROs) have recently gained greater credibility with regulatory bodies aiming to standardise their use and interpretation in RCTs, thereby supporting medicinal product submissions. For this reason, the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) have released guidelines. This review paper provides an overview of the current perspectives and views on these guidelines.MethodTo evaluate the FDA and EMEA PRO guidelines, 47 expert responses to the FDA guidance were qualitatively reviewed. Two reviewers independently extracted data from these letters and checked these responses to warrant consistency and agreement in the evaluation process. A PubMed literature review was systematically examined to obtain supporting evidence or related articles for both the guidance documents.ResultsGenerally, there is agreement between regulatory authorities and the research community on the contents of the FDA and EMEA PRO draft guidance. However, disagreements exist on significant philosophical topics (e.g. the FDA focuses more on conceptual models and symptoms than the EMEA) and design topics (e.g. the FDA is more restrictive on issues of recall bias, blinding of oncology trials and degrees of psychometric validation than researchers and the EMEA). This could influence the approval of PRO claims.ConclusionPRO guidance from the EMEA and FDA has been valuable, and has raised the profile and active debate of PROs in oncology. However, our review of the current opinion shows that there are controversial aspects of the guidance. Consequently, greater latitude should be given to how the guidance is interpreted and applied.     

Osteonecrosis of the jaw and the role of macrophages

Nitrogen-containing bisphosphonates have been associated with the development of osteonecrosis of the jaws (ONJ), but the lack of reliable epidemiological data and appropriate animal models has restricted our understanding of ONJ pathophysiology and limited its management. The best available information is from histopathologic findings, which implicate bone necrosis and infection, although it is not clear which is primary. However, there are data suggesting that macrophages could well be the central factor in allowing the infection to develop first, followed by local necrosis, which could also account for the development of ONJ in patients treated with denosumab, a human monoclonal antibody to the receptor activator of nuclear factor-κB ligand. This review examines the evidence that macrophages could play a prominent role in development of ONJ and the proposal that it may be more appropriate to view ONJ as a drug and not only a bisphosphonate-related complication.     

Urbanization and the incidence of abnormalities of squamous and glandular epithelium of the cervix

BACKGROUND: The large data bases of the Dutch cervical screening program can be exploited to establish the relation between urbanization and the incidence of abnormalities of the squamous and glandular epithelium, including mild or greater changes of the squamous and glandular epithelium of the cervix. METHODS: Six cytology laboratories in the context of the Dutch cervical screening program screened over 190,000 cervical smears. Urbanization (place of residence) data were derived from postal codes. All smears were coded with the Dutch national coding system, the Dutch national classification system KOPAC, in which squamous abnormalities are coded S4-S9, and glandular cell changes are coded G4-G9. From the scores per 1000 screened women, the relative risk (RR) of living in a large city compared with living in rural areas was calculated. To investigate a trend in incidence in relation to urbanization, the Schaafsma method was used. RESULTS: Of the smears with positive cytology, mild squamous dysplasia (S4) had the highest incidence per 1000 screened women (4.32), and the lowest incidence was found for adenocarcinoma (in situ; G7/G9; RR, 0.07). The RR for urban women ranged from 1.73 for moderate squamous dysplasia (S5) to 7.55 for adenocarcinoma (in situ; G7/G9). For smears with positive cytology for both squamous and glandular abnormalities, the Schaafsma method indicated a significant positive trend. CONCLUSIONS: The incidence of squamous and glandular abnormalities are maximal in women who live in a large city, which, in The Netherlands, is where there also is a population at high risk for human papillomavirus and bacterial vaginosis.