多发性基底细胞癌光动力疗法的临床观察

多发性基底细胞癌光动力疗法的临床观察邢汝东ＭｉｋｅＳｍｉｔｈ△关键词基底细胞癌光动力疗法中图号Ｒ７３０．２６１Ｒ７３０．５７光动力疗法（ｐｈｏｔｏｄｙｎａｍｉｃｔｈｅｒａｐｙ，ＰＤＴ）是近年开展的快速、无创伤治疗肿瘤的一种新方法，根据肿瘤组织吸收外源...     

皮肤鳞状细胞癌治疗靶点的研究进展

作为一种常见的非黑色素瘤皮肤癌,晚期皮肤鳞状细胞癌（cutaneous squamous cell carcinoma,cSCC）的治疗仍是急需 解决的临床难题。尽管cSCC并非靶向治疗研究的重点,但近年来随着靶向治疗在其他肿瘤的研究和应用的深入,cSCC的靶向 治疗也取得新的进展,特别是针对PD-1的免疫检查点疗法已经获准进入临床应用;针对另一些靶点如细胞表皮生长因子受体 （EGFR）、血管内皮生长因子受体（VEGFR）、胰岛素样生长因子受体（IGFR）以及肿瘤抗原MAGE-A3等的疗法也正在临床试用; TP53、CDKN2A和Notch等cSCC频繁突变的基因,以及RAS-RAF-MEK-ERK与PI3K-AKT-mTOR等通路相关信号分子和端粒酶 等也是具有研发潜力的cSCC治疗靶点,针对这些靶点开展深入研究有可能为cSCC的治疗找到新的途径。     

光动力疗法对恶性皮肤肿瘤及癌前期皮肤病的疗效及不良反应分析

目的 分析光动力疗法治疗恶性皮肤肿瘤及癌前期皮肤病的临床效果及不良反应。方法 选取恶性皮肤肿瘤及癌前期皮肤病患者72例,均采用光动力疗法,统计疗效、不良反应、复发情况。结果 采用光动力疗法治疗后,总有效率为95.83%(69/72);72例患者,采用光动力疗法治疗后,照射部位大部分产生红肿、灼热、瘙痒症状,其中灼热56例(77.78%),溃烂1例(1.39%),瘙痒58例(80.56%),红肿55例(76.39%);治疗后每月行1次检查,行1～2年随访,入选72例患者随访期间有9例复发,复发率为12.5%,其中皮肤黑色素瘤复发率为10.53%(2/19),皮肤基底细胞癌复发率为6.25%(1/16),乳腺癌皮肤转移复发率为17.65%(3/17),皮肤血管肉瘤复发率为10.00%(1/10),皮肤鳞状细胞癌复发率为10.00%(1/10)。结论 采用光动力疗法治疗恶性皮肤肿瘤及癌前期皮肤病患者临床效果显著,多为灼热、瘙痒等轻微不良反应,无严重不良反应,具有应用安全,且复发率低,预后效果确切。     

紫外线致非黑色素瘤皮肤癌的作用机制研究进展

非黑色素瘤皮肤癌（NMSC）是最常见的皮肤癌类型，占全世界每年诊断的所有恶性肿瘤的 1/3。最常见的非黑色素瘤皮肤癌包括基底细胞癌（BCC）、鳞状细胞癌（SCC）和光化性角化病（AK）。虽然这些肿瘤导致的死亡率很低，但非黑色素瘤皮肤癌的高发病率已经引起了相当多的患者死亡，对公共健康和医疗保健成本产生了重大影响。许多危险因素涉及非黑色素瘤皮肤癌的发病机制，包括紫外线辐射，遗传和分子改变，免疫抑制等，其中紫外线辐射在非黑色素瘤皮肤癌的发生发展中起重要作用。所以，我们的研究重点关注紫外线，并详细分析了紫外线致非黑色素瘤皮肤癌的作用机制。尽管尚未完全了解非黑色素瘤皮肤癌的发病机制，但紫外线是非黑色素瘤皮肤癌已知的重要危险因素，通过采取防晒措施可有效预防非黑色素瘤皮肤癌的发生发展。现对近年来紫外线致非黑色素瘤皮肤癌的作用机制作一综述，以期通过预防措施和策略，包括个人行为改变和公共教育计划，减少非黑色素瘤皮肤癌的发病率。     

皮肤癌变，哪些是祸根

皮肤癌在我国的发病率不高但在白种人，尤其在高加索人种中是十分常见的恶性肿瘤．皮肤癌常分为非黑色素瘤皮肤癌（NMSC)和恶性黑色素瘤（MM)两种．前者最常见的两种类型为基底细胞癌（BCC）和鳞状细胞癌（SCC)．虽然恶性黑色素瘤发病率不高．但它的恶性程度很高，并且其发病率在全球范围内迅速增     

光动力联合冷冻对非黑色素瘤性皮肤癌的临床疗效

目的探究光动力联合冷冻对非黑色素瘤性皮肤癌(NMSC)患者的临床疗效。方法根据治疗方案的不同将96例NMSC患者分为研究组(n=50)和对照组(n=46),对照组采用5-氨基酮戊酸光动力疗法(ALAPDT)治疗,研究组采用ALA-PDT联合冷冻治疗。比较两组患者的视觉模拟评分量表(VAS)评分、外观满意度、临床疗效、不良反应发生情况和3年无进展生存情况。结果研究组患者的VAS评分略高于对照组,但差异无统计学意义(P﹥0.05)。研究组患者的外观满意度、治疗总有效率均高于对照组,差异均有统计学意义(P﹤0.05)。研究组患者的不良反应总发生率略高于对照组,但差异无统计学意义(P﹥0.05)。两组患者的3年无进展生存时间和3年无进展生存率比较,差异均无统计学意义(P﹥0.05)。结论光动力联合冷冻治疗非黑色素瘤性皮肤癌的临床疗效较好,有利于皮损外观的恢复,患者的满意度高,不良反应少,患者的无进展生存期较长,可为不适宜行手术治疗的非黑色素瘤性皮肤癌患者提供新的治疗思路。     

激光光纤介入的光动力疗法治疗皮肤鳞状细胞癌的实验研究

目的：评价激光光纤介入内照射5-氨基酮戊酸盐酸盐-光动力疗法(OFI-ALA-PDT)和传统外照射5-氨基酮戊酸盐酸盐-光动力疗法(ALA-PDT)治疗皮肤鳞状细胞癌的临床疗效及不良反应。方法：收集我院门诊48例鳞状细胞癌患者，随机分为光纤内照射组和传统外照射组，光纤内照射组在外用5-氨基酮戊酸盐酸盐后运用光纤插入靶皮损内，进行光动力治疗，而传统外照射组外用5-氨基酮戊酸盐酸盐后进行光动力治疗，观察两组患者的临床疗效、复发率以及不良反应。结果：光纤内照射组的临床疗效明显高于传统外照射组，差异有统计学意义（P<0.05），复发率与传统外照射组相比差异无统计学意义（P>0.05），不良反应发生率低于传统外照射组，两者差异有统计学意义（P<0.05）。结论：OFI-ALA-PDT治疗皮肤鳞状细胞癌疗效确切，美容效果佳，治疗高分化鳞状细胞癌尤其是年老体弱、美容要求高的患者亦有一定的疗效，且治疗过程患者耐受性好，与ALA-PDT相比有一定优势。     

抑癌多糖——LAK细胞活性增强剂

抑癌多糖──ＬＡＫ细胞活性增强剂李金锋综述黄信孚林本耀审校北京医科大学临床肿瘤学院（北京市１０００３６）ＬＡＫ／ＩＬ－２疗法临床应用治疗晚期恶性肿瘤日渐增多，且取得一定疗效，尤其对恶性黑色素瘤、肾细胞癌、淋巴瘤等有效率达２０％～５７％［１，２］。但此...     

68例皮肤恶性肿瘤与癌前病变的临床分析

目的 分析皮肤癌的临床病理学特点.方法 回顾性分析68例皮肤癌患者的临床资料.结果 68名患者中,以皮肤鳞癌、皮肤基底癌和皮肤转移性肿瘤较多;男性较女性患者更易患有皮肤恶性肿瘤及癌前病变;皮肤基底癌、皮肤鳞癌、皮肤黑色素瘤、日光性角化病、增殖性红斑以男性患者为主;皮肤转移癌、蕈样肉芽肿、Bowen病以女性患者为主;特别是癌前病变患者多见于男性.面部以皮肤基底癌、皮肤鳞癌为主,躯干前部以皮肤鳞癌和皮肤转移癌为主,躯干后部以皮肤鳞癌为主,四肢以皮肤鳞癌,皮肤黑色素瘤为主,臀部以皮肤鳞癌为主,乳腺以皮肤鳞癌、皮肤黑色素瘤、蕈样肉芽肿及Bowen病为主.结论 分析皮肤癌的临床病理学特点,更好地认识皮肤恶性肿瘤及皮肤癌前病的发病特点,为今后临床皮肤癌研究及治疗提供进一步临床理论依据.     

基底细胞癌诊断及治疗研究进展

基底细胞癌(basal cell carcinoma,BCC）是来自基底细胞层的恶性肿瘤,它与紫外线照射有着密切的关系,因此颜面部为基底细胞癌的好发部位。组织病理学检查是诊断基底细胞癌的金标准,然而基底细胞癌早期病变根据临床特点很容易被误诊,近年来随着皮肤影像学技术的发展,非侵入性诊断工具,如皮肤镜、反射式共聚焦显微镜、高频超声等的应用,让更多的早期基底细胞癌被发现,从而减少了良性皮肤病变的活检次数。治疗方案的选择主要依据肿瘤的组织病理学类型、大小、部位以及浸润程度所决定,手术切除为目前最主要的治疗手段,除此之外化疗、药物、光动力、放疗、电灼术、冷冻、激光消融及联合治疗也是较常用的方法。     

Role of radiotherapy in the management of organ transplant recipients diagnosed with non‐melanoma skin cancers

Organ transplantation has had a major effect on the lives of thousands of patients worldwide. In Australia and New Zealand, over 13 000 patients have become organ transplant recipients (OTR). Following transplantation, patients require lifelong immunosuppression to prevent organ rejection. The loss of immune surveillance results in OTR experiencing a higher incidence of infection and malignancy in comparison with the general (immunocompetent) population. Non‐melanoma skin cancer (NMSC) is the most common malignancy worldwide, arising most often on the sun‐exposed head and neck. Organ transplant recipients experience a higher incidence of NMSC when compared with the general population and a higher incidence of squamous cell carcinoma compared with basal cell carcinoma. Organ transplant recipients also develop NMSC at a younger age and experience multiple new NMSC. Australians experience the highest incidence of NMSC in the world with a consequence that NMSC arising in OTR can lead to significant morbidity and even mortality. Radiation oncologists treating patients with skin cancer will almost certainly make recommendations in the setting of NMSC arising in OTR. The aim of this article is to discuss the role of radiotherapy in the management of OTR diagnosed with NMSC. The emphasis will be on the treatment of patients with a high‐risk NMSC (e.g. squamous cell carcinoma, Merkel cell carcinoma, unfavourable basal cell carcinoma) because this reflects the most common clinical scenario in which a recommendation of radiotherapy, usually adjuvant, may be considered.     

Update on non-melanoma skin cancer and the value of dermoscopy in its diagnosis and treatment monitoring

Dermoscopy has become an integrative part of the clinical examination of skin tumors. This is because it significantly improves the early diagnosis of melanoma and non-melanoma skin cancer (NMSC) including basal cell carcinoma and keratinocyte skin cancer compared with the unaided eye. Besides its value in the noninvasive diagnosis of skin cancer, dermoscopy has also gained increased interest in the management of NMSC. Dermoscopy has been used in the preoperative evaluation of tumor margins, monitoring of the outcomes of topical treatments and post-treatment follow-up. This article provides an update on NMSC with special emphasis on dermoscopy in the diagnosis and management of basal cell carcinoma, actinic keratosis, Bowens’ disease and squamous cell carcinoma.     

Trends in the incidence of nonmelanoma skin cancer in Denmark 1978–2007: Rapid incidence increase among young Danish women

Nonmelanoma skin cancer (NMSC) is the most common cancer among Caucasian populations worldwide, and incidence rates are increasing. However, NMSC data are not routinely collected by cancer registries, but Denmark has extensive registration of NMSC in two nationwide population‐based registries. We assessed incidence trends of NMSC in Denmark from 1978 to 2007. Data for basal cell carcinoma ( BCC) and squamous cell carcinoma (SCC) were obtained from the Danish Cancer Registry and the Danish Registry of Pathology. For both genders, age‐specific incidence rates and overall incidence rates, age‐adjusted according to the World standard population were calculated based on combined data from the two registries. For both genders, a high increase in both BCC and SCC incidence was observed over time. Between 1978 and 2007, the age‐adjusted BCC incidence increased from 27.1 to 96.6 cases per 100,000 person‐years for women and from 34.2 to 91.2 cases for men. The SCC incidence increased from 4.6 to 12.0 cases per 100,000 person‐years for women and from 9.7 to 19.1 cases for men. For both BCC and SCC, women experienced a higher average annual percentage incidence change than men. Furthermore, the average annual percentage change in BCC incidence among persons below 40 years was significantly higher compared to older persons, especially for women. These trends may lead to an alarming NMSC incidence increase over time as population ages and will have major implications for future healthcare services. Our findings underline the need for improved preventive strategies to hamper the increasing NMSC incidence.     

Deaths from non-melanoma skin cancer in Western Australia

Objectives  Non-melanoma skin cancer (NMSC) is common, slow growing, and rarely metastasizes. However, there are still nearly 400 deaths from NMSC in Australia annually. We aimed to investigate the accuracy of NMSC death coding and to describe the characteristics of these deaths and the potential for prevention. Methods  Histology reports for all deaths coded as NMSC (ICD-10 C44.0-C44.9) by the Western Australian Cancer Registry for the years 1996–2005 were reviewed for type of cancer, body site (primary tumor and metastases), and level of available documentation. Results  Of 368 deaths recorded as being due to NMSC only 3 were found to be miscoded. An additional 53 deaths contained inadequate information to confirm NMSC as the cause of death. Of the confirmed cases, 219 were due to squamous cell carcinoma, 53 to Merkel cell carcinomas, and 40 to other skin cancers. Cases were mainly males and were elderly. Most of the primary squamous and Merkel cell carcinomas were in areas of maximum sun exposure (face, ears, and hands, and scalp in males). Conclusions  Misclassification of NMSC deaths in WA was minimal. The majority of NMSC deaths were due to squamous cell carcinomas; had primary sites associated with significant sun exposure; and occurred in older men.     

MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project

Background:

The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics.

Methods:

Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses.

Results:

Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24–1.76), 1.39 (1.15–1.69) and 1.61 (1.35–1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19–1.70) for V60L to 2.66 (1.06–6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair.

Conclusions:

Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype.     

Prospective study of genital human papillomaviruses and nonmelanoma skin cancer

Genital high‐risk human papillomaviruses (HPVs) cause cervical cancer and are also found in a small proportion of nonmelanoma skin cancers (NMSCs). We used cancer registry linkages to follow the 856,000 serum donors included in the Southern Sweden Microbiology Biobank or the Janus Biobank in Norway, for incident skin cancers occurring up to 30 years after serum donation. Serum samples taken before diagnosis of squamous cell carcinoma (SCC) (N = 633), basal cell carcinoma (BCC) (N = 1990) or other NMSC (N = 153) and matched samples from control donors were tested for antibodies to the genital HPV types 16 and 18. Both HPV 16 and 18 were associated with increased risk for SCC [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1–2.6 and OR 1.7, 95% CI 1.1–2.5, respectively] and other NMSC (OR 2.3, 95% CI 1.0–5.2 and OR 3.5, 95% CI 1.4–8.7, respectively), but not for BCC. Tumor blocks from HPV16 or 18 seropositive cases were tested with real‐time polymerase chain reaction for presence of HPV16 or 18 DNA. No HPV18 DNA was found and only four of 79 SCC cases (two of which were from the perineum/perianal area), one of 221 BCC cases and zero of five cases with other NMSC contained HPV16 DNA. In conclusion, we found prospective evidence that HPV16 and 18 antibodies associate with SCC and other NMSC risk, but not with BCC risk. As only a small proportion of seropositive subjects had evidence of the corresponding HPV DNA in the tumor, most of this excess risk is likely to be due to confounders associated with genital HPV infection.     

Non-melanoma skin cancers and glucocorticoid therapy

Non-melanoma skin cancer (NMSC) is an important cause of morbidity and long-term mortality in organ transplant recipients receiving immunosuppressive drugs such as azathioprine and cyclosporin, often combined with adrenocortical steroids (glucocorticoids). At lower doses, glucocorticoids alone are prescribed for other conditions including musculoskeletal, connective tissue and respiratory disorders. Presently, it is unknown whether patients taking glucocorticoids are at an increased risk of skin malignancies. In a population-based case-control study in New Hampshire, USA, we compared use of glucocorticoids in 592 basal cell carcinoma (BCC) and 281 squamous cell carcinoma (SCC) cases and in 532 age and gender matched controls; neither cases nor controls had a history of organ transplantation. Participants underwent a structured personal interview regarding history of medication use and skin cancer risk factors. We used unconditional logistic regression analysis to compute odds ratios associated with glucocorticoid use for 1 month or longer while controlling for potential confounding factors. Risk of SCC was increased among users of oral glucocorticoids (adjusted odds ratio = 2.31; 95% CI = 1.27, 4.18), and risk of BCC was elevated modestly (adjusted odds ratio = 1.49; 95% CI = 0.90, 2.47). In contrast, risk of both SCC and BCC were unrelated to use of inhaled steroids. Our data suggest that use of oral glucocorticoids may increase risk of NMSC, and SCC in particular, among patients other than organ transplant recipients. We hypothesize that immunosuppression induced by oral glucocorticoids may allow these cancers to emerge from immunosurveillance.     

Squamous cell carcinoma of the skin: Emerging need for novel biomarkers

The incidence of non-melanoma skin cancers (NMSC) is rising worldwide resulting in demand for clinically useful prognostic biomarkers for these malignant tumors, especially for invasive and metastatic cutaneous squamous cell carcinoma (cSCC). Important risk factors for the development and progression of cSCC include ultraviolet radiation, chronic skin ulcers and immunosuppression. Due to the role of cumulative long-term sun exposure, cSCC is usually a disease of the elderly, but the incidence is also growing in younger individuals due to increased recreational exposure to sunlight. Although clinical diagnosis of cSCC is usually easy and treatment with surgical excision curable, it is responsible for the majority of NMSC related deaths. Clinicians treating skin cancer patients are aware that certain cSCCs grow rapidly and metastasize, but the underlying molecular mechanisms responsible for the aggressive progression of a subpopulation of cSCCs remain incompletely understood. Recently, new molecular markers for progression of cSCC have been identified.     

Measures of cutaneous human papillomavirus infection in normal tissues as biomarkers of HPV in corresponding nonmelanoma skin cancers

Cutaneous human papillomavirus (HPV) may be associated with the development of nonmelanoma skin cancer (NMSC), as suggested by reports of HPV DNA in NMSC tumors. HPV has also been investigated as an NMSC risk factor in epidemiologic studies, although findings vary across studies that used different biomarkers of HPV infection in normal tissues. To identify appropriate biomarkers for use in future epidemiologic studies, we conducted a sampling validation study. NMSC tumor tissue was obtained from 20 patients with pathology-confirmed basal or squamous cell carcinoma of the skin, in addition to several normal tissues, including eyebrow hairs, normal skin swabs obtained using multiple techniques, normal skin punch and shave biopsies, and serum for antibody measurement. Presence of cutaneous HPV DNA in tissues was measured with multiplex PCR using HPV type-specific primers and array primer extension (APEX) for HPV typing. Antibody detection was based on glutathione-S-transferase capture ELISA in combination with fluorescent bead technology. Using HPV DNA in tumor tissues as a gold standard, sensitivity and specificity were calculated for each measure of HPV infection in normal tissues. beta-Papillomavirus DNA was observed in tumor tissues in 60% of patients. The normal skin punch biopsy demonstrated optimal sensitivity (75%) and specificity (75%). Biomarkers obtained using less-invasive techniques demonstrated poor specificity when considered individually, although specificity improved when biomarkers were combined. Based on the current case series, the combinations of antibodies+eyebrow hairs or antibodies+eyebrow hairs+Dacron swabs are the optimal, minimally invasive markers of cutaneous HPV infection for use in epidemiologic studies.     

Evolving Role of Systemic Therapies in Non-melanoma Skin Cancer

Keratinocyte cancers – basal and cutaneous squamous cell carcinoma (BCC, cSCC) – are the most common forms of non-melanoma skin cancer (NMSC) and there has been a significant increase in their incidence globally in recent decades. Although the majority of BCC and cSCC are cured with conventional surgery or radiotherapy, certain tumour or patient-determined factors may result in these modalities being inadequate or inappropriate, for example, locally advanced or metastatic disease, high tumour multiplicity, patient comorbidities and patient preferences. In these clinical circumstances, systemic treatment may be indicated, and over the past 10 years a number of new systemic agents have been approved. Nonetheless, effective systemic therapy for keratinocyte cancers remains an area of significant unmet clinical need. Improved understanding of the molecular and immune pathogenesis underlying tumour growth and development is critical for driving future advances and is a research priority. The aim of this review is to provide clinicians with an overview of systemic treatments for BCC and cSCC and will focus on current evidence for conventional chemotherapy, targeted therapies, immunotherapy, adjuvant and neoadjuvant therapy, chemoprevention and future prospects for novel systemic treatment approaches.