膀胱癌是美国男性中第四大最常见的癌症，他们开发了大约90%的高级别非肌肉侵润性疾病（NMIBC）的原位癌（CIS）。吸烟和职业致癌物是众所周知的原因。对于没有已知风险因素的女性来说，膀胱癌可以视为哨兵环境癌症之一。由于其高复发率，也是治疗成本最高的癌症之一。近两十年来没有发生任何治疗创新；全球供应短缺的卡介苗（BCG）或丝裂霉素-C（MIT-C）的膀胱内注射在约60%的病例中有效。不耐BCG和MIT-C的病例经常接受膀胱切除术，这个程序对生活方式和潜在并发症有很多影响。约翰霍普金斯大学最近完成了一个关于欧亚冬青在癌症患者中的小型Ⅰ期试验，这些患者已用尽了已知的治疗，试验证实其安全性，25％的患者病情没有进展。该研究以一位75岁的女性患者为例，她患有高级别CIS的膀胱癌，已经尝试了BCG治疗但表现为无效。治疗方案包括药理性抗坏血酸（PA）、欧亚冬青、营养补充剂、运动和其他补充治疗。在进行了包括手术、细胞和病理学评估的治疗后，患者体验到了78个月的无癌症结果。这项研究是首个报告的通过综合治疗方案实现高级别NMIBC完全缓解的实例，并包括有关可能机制的药理学信息。在BCG不足，BCG和MIT-C反应不良的高比例，以及亚洲人参和营养补充剂相对经济且高效的情况下，临床医生应认真考虑采用这些综合功能医学治疗方案治疗BCG -和MIT-C-反应性NMIBC。需要进行进一步研究，包括标准化方法，以系统评估组合疗法-盲目和非盲目，欧亚冬青制备的命名法，剂量，浓度，管理方案和治疗时长，针对癌症类型和其他方面。

Bladder cancer is the fourth-most-common cancer in males in the U.S., who develop about 90% of the high-grade, carcinoma in situ (CIS) of non-muscle involved disease (NMIBC). Smoking and occupational carcinogens are well-known causes. For females without known risk factors, bladder cancer can be regarded as a sentinel environmental cancer. It's also one of the costliest to treat due to its high rate of recurrence. No treatment innovations have occurred in nearly two decades; intravesical instillation of Bacillus Calmette-Guerin (BCG), an agent in short supply globally, or Mitomycin-C (MIT-C) is effective in about 60% of cases. Cases refractory to BCG and MIT-C often undergo cystectomy, a procedure with numerous impacts on life styles and potential complications. The recent completion of a small Phase I trial of mistletoe in cancer patients that have exhausted known treatments at Johns Hopkins provides corroboration of its safety, with 25 % showing no disease progression.The study examined the benefits of pharmacologic ascorbate (PA) and mistletoe for a nonsmoking female patient with an environmental history of NMIBC refractory to BCG, in a non-smoking female with exposures in childhood and early adult life to several known carcinogens, including ultrafine particulate air pollution, benzene, toluene, and other organic solvents, aromatic amines and engine exhausts, and possibly arsenic in water.The research team performed an integrative oncology case study on pharmacologic ascorbate (PA) and mistletoe, both agents shown to activate NK cells, enhance growth and maturation of T-cells, and induce dose-dependent pro-apoptotic cell death, suggesting shared and potentially synergistic mechanisms.The study began at the University of Ottawa Medical Center in Canada with treatment continuing over six years at St. Johns Hospital Center in Jackson, Wyoming, and George Washington University Medical Center for Integrative Medicine, with surgical, cytological, and pathological evaluations at University of California San Francisco Medical Center.The patient in the case study was a 76-year-old, well-nourished, athletic, nonsmoking female with high-grade CIS of the bladder. Her cancer was considered to be a sentinel environmental cancer.Intravenous pharmacologic ascorbate (PA) and subcutaneous mistletoe (three times weekly) and intravenous and intravesical mistletoe (once weekly) were employed for an 8-week induction treatment, using a dose-escalation protocol as detailed below. Maintenance therapy was carried out with the same protocol for three weeks every three months for two years.The patient has experienced a cancer-free outcome following 78 months of treatments that incorporated intravesical, intravenous, and subcutaneous mistletoe; intravenous PA; a program of selected nutraceuticals; exercise; and other supplementary treatments.This study is the first reported instance of combined treatments to achieve complete remission for high-grade NMIBC refractory to BCG and MIT-C, using intravesical, subcutaneous, and intravenous mistletoe and intravenous PA. It includes pharmacological information on possible mechanisms. In light of the global shortage of BCG, the high proportion of cases refractory to BCG and MIT-C, the unproven use of costly off-label pharmaceuticals, such as gemcitabine, and the relative cost-effectiveness of mistletoe and PA, clinicians should give serious consideration to employing these combined functional medicine treatments for BCG- and MIT-C-refractory NMIBC. Further research is needed with additional patients that can advance our understanding, including standardization of methods for systematically evaluating combined therapies-blinded and non-blinded, nomenclature regarding mistletoe preparation, doses, concentrations, regimes of administration, lengths of treatment, targeted cancer types, and other aspects.