Vitamin C enhances tumor inhibitory effects of Gefitnib in non small cell lung cancer

Vitamin C enhances tumor inhibitory effects of Gefitnib in non small cell lung cancer.

Abstract

A persistent human papillomavirus (HPV) infection of a high-risk type is necessary for cervical cancer to develop. The severity of the diagnosis, together with colposcopy findings, determines the standard for treatment, and ablative or excisional options may be recommended. Escharotic treatment, together with an oral, anticarcinogenic HPV protocol and a vaginal-suppository protocol, is an alternative treatment, especially for those women of childbearing age who are concerned about the possibility of obstetrical complications associated with the use of loop electrosurgical excision (LEEP). The aim of the current case study was to observe the effect of an ablative escharotic treatment for a woman with severe dysplasia, cervical intraepithelial neoplasia grade 3 (CIN3). A 28-y-old female visited the National College of Natural Medicine clinic to obtain suggestions for alternative treatments following a satisfactory colposcopy and a biopsy revealing a high-risk HPV effect, severe dysplasia CIN3, and a positive endocervical curettage (ECC). She refused the recommended standard of care, a LEEP, because of concerns about the potential for future obstetrical complications. As an alternative, she elected to receive an escharotic treatment at a frequency of 2 treatments/wk for 5 wk. In addition to the escharotic treatment, she followed an oral protocol consisting of vitamins and botanical medicine for 1 y and she completed a 12-wk regime of vaginal suppositories following the escharotic. The authors followed her for 2 y. The woman’s Papanicolaou (Pap) test at the 6-mo follow-up revealed negative cervical cytology for intraepithelial lesion or malignancy, and her follow-up ECC was negative. Liquid-based Pap results were normal, and HPV testing was negative at her 1-y follow-up. Her Pap continued to remain normal at her 2-y follow-up. For women with high-grade cervical neoplasias and positive ECCs, with satisfactory colposcopies, escharotic treatment, accompanied by oral supplementation, holds promise as an effective alternative to LEEP and other excisional procedures.

Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the United States, accounting for 75% of the 20 million STIs reported yearly. Acquired by skin-to-skin contact, it is now estimated that nearly all sexually active persons will contract at least 1 type of HPV at some point in their lifetimes. Of the 100-plus HPV genotypes (types), 40 can cause infections of the genital area. Approximately 90% of these HPV infections are transient, asymptomatic, and resolve without treatment. Several, however, are considered high-risk strains accounting for persistent infections and more serious HPV-associated diseases, including cervical, anal, vaginal, vulvar, and penile cancers. With more than 12 000 cases diagnosed annually in the United States, cervical cancer is the most common of the HPV-associated cancers. It affects roughly 8% of the female population and results in fatalities in nearly one-third of the invasive cases of cervical cancer diagnosed yearly.,

A persistent HPV infection of a high-risk type is necessary for cervical cancer to develop. Approximately 12 high-risk HPV types can lead to cervical cancer, of which types 16 and 18 are the most oncogenic. The goal of cytology—Papanicolaou (Pap) testing—is to detect precancerous abnormalities of the cervix.Cervical squamous intraepithelial lesions (CSIL) are stratified based on the degree to which cells have lost their uniformity and architectural orientation. In 2012, the American Society for Colposcopy and Cervical Pathology (ASCCP) issued an updated consensus for the management of early detection of precancerous lesions, cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS). Depending on a woman’s age, cytology findings, and other risk factors, ASCCP recommends molecular testing for high-risk HPV, together with cytology, to increase sensitivity and identify those women with a high-risk HPV infection. Further investigation using colposcopy and biopsy may be recommended based on abnormal cytology, HPV testing, and individual risk factors. Histological characteristics of CIN are placed in a 3-tiered system based on severity. CIN1 is considered a low-grade lesion, while CIN2 and CIN3 are high-grade lesions. The severity of the diagnosis, together with colposcopy findings, determines the standard for treatment, and ablative or excisional options may be recommended. Ablative treatments conventionally consist of cryotherapy or laser ablation. Excisional procedures consist mainly of cold knife, laser conization, and loop electrosurgical excision (LEEP), also known as large-loop excision of the transformation zone (LLETZ). Although LEEPs are shown to be equally as effective as ablative treatments, they are associated with a higher risk of obstetrical complications.

Cervical stenosis, preterm premature rupture of membranes (pPROM), and preterm delivery are the most common obstetrical complications associated with LEEP procedures. The volume of tissue removed and a history of loop excision are independent predictors of cervical stenosis after LEEP, at an increased risk of 1.32% and 17.4%, respectively. After a single LEEP procedure, a woman’s risk of pPROM, with a subsequent preterm delivery (<37 wk), is 1.9% higher compared with untreated women., For a woman with a history of LEEP, the risk of preterm delivery increases after 34 weeks and is directly related to the depth of previous excision(s), the number of LEEP procedures received, and multiple gestations.,Theoretically, excisional therapies compromise cervical integrity, with a subsequent decrease in tensile strength, by disruption of the cervical glands and stroma. This disruption may lead to a decreased ability to dilate properly during labor in the case of cervical stenosis, increase the potential for ascending infections and changes to the vaginal flora in cases of pPROM, and cause premature dilation in cases of preterm delivery.

Escharotic treatment is an ablative therapy that has been used to treat cervical dysplasia. Historically, it was used before 2001 as a treatment option for CIN1 and an alternative treatment for those women with CIN2 and CIN3 who refused the excisional therapies that are the standard of care. After ASCCP’s 2001 consensus guidelines were published, local therapies, including ablative treatments, were no longer recommended in cases of CIN1. According to ASCCP’s 2006 consensus guidelines, ablative therapies were considered acceptable in cases of CIN2 or CIN3 with a satisfactory colposcopy. In 2006, inclusion of ablative therapies for women with CIN2 and CIN3 became particularly important as an option for women who had not completed their families.

Escharotic treatment, together with an oral, anticarcinogenic HPV protocol and a vaginal-suppository protocol, is an alternative treatment, especially for those women of childbearing age who are concerned about the possibility of obstetrical complications associated with the use of LEEP. This combined treatment was first studied in 1991 by Hudson, who examined the combined use of escharotic treatment with botanical and nutritional oral supplementation and a vaginal suppository treatment for individuals with cervical carcinoma in situ. In Hudson’s study, 4 of the 7 women treated showed ongoing remission after 1 year.

The largest study to date involved the use of an escharotic treatment combined with individualized treatment plans based on cytological and histological findings of cervical dysplasia. Out of the 43 women treated, 38 returned to normal findings, 3 had partial improvements, and 2 were unchanged from initial diagnosis at the 2-year follow-up. Escharotic treatment was also examined in a 2009 case study, in which a woman received treatment for CIN2/3, with long-term remission reported at the 5-year follow-up.

Escharotic treatment involves the topical application of an herbal escharotic agent to the lesion, which causes a burn on physical contact, thus destroying neoplastic growth. The abnormal tissue is subsequently sloughed off, and the resultant scab is known as an eschar. Criticisms of escharotic treatments in medical literature originate from cases that were not under the care of licensed health care professionals with expertise in the areas of gynecology and alternative medicine, but rather these criticisms address cases in which individuals self-prescribed, independently purchased, and applied escharotic treatments available on the Internet. When performed by an appropriately trained medical provider, escharotic treatment accompanied by an oral anticarcinogenic protocol has been shown to have a positive outcome.

This study was performed at the National College of Natural Medicine (NCNM) and the Helfgott Research Institute in Portland, OR. The purpose of the current case study was to explain the procedure and effect of an ablative escharotic treatment for a woman with severe dysplasia, CIN3. Escharotic treatment holds promise as an alternative for women of childbearing age who are concerned about the potential obstetrical complications associated with excisional therapies, especially with LEEP. That said, the obstetrical complications of escharotic treatment are unknown.