Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Surgical excision or laser therapy are possible treatments. Surgical excision alone was effective for controlling VC, but elective neck dissection was not necessary even in patients in the advanced stages.
Induction chemotherapy is the treatment adapted for shrinking the tonsil tumor. It is given prior to other treatments, hence, the term induction. After the therapy is completed, the patient is asked to rest and is evaluated over a period of time. Then the patient is given chemo-radiation therapy (a combination of chemotherapy and radiation) to completely destroy the tumor cells.
Early radio-sensitive tumors are treated by radiotherapy along with irradiation of cervical nodes. The radiation uses high-energy X-rays, electron beams, or radioactive isotopes to destroy cancer cells.
Surgical excision (removal) of the tumor is usually recommended if the tumor is small enough, and if surgery is likely to result in a functionally satisfactory result. Radiation therapy with or without chemotherapy is often used in conjunction with surgery, or as the definitive radical treatment, especially if the tumour is inoperable. Surgeries for oral cancers include:
- Maxillectomy (can be done with or without orbital exenteration)
- Mandibulectomy (removal of the mandible or lower jaw or part of it)
- Glossectomy (tongue removal, can be total, hemi or partial). When glossectomy is performed for smaller tumors (< 4 cm), the adequacy of resection (margin status) is best assessed from the resected specimen itself. The status of the margin (positive/tumor cut through versus negative/clear margin) obtained from the glossectomy specimen appears to be of prognostic value, while the status of the margin sampled from the post-glossectomy defect is not. The method of margin sampling appears to correlate with local recurrence: preference for tumor bed/defect margins may be associated with worse local control.
- Radical neck dissection
- Mohs surgery or CCPDMA
- Combinational, e.g. glossectomy and laryngectomy done together
- Feeding tube to sustain nutrition
Owing to the vital nature of the structures in the head and neck area, surgery for larger cancers is technically demanding. Reconstructive surgery may be required to give an acceptable cosmetic and functional result. Bone grafts and surgical flaps such as the radial forearm flap are used to help rebuild the structures removed during excision of the cancer. An oral prosthesis may also be required. Most oral cancer patients depend on a feeding tube for their hydration and nutrition. Some will also get a port for the chemo to be delivered. Many oral cancer patients are disfigured and suffer from many long term after effects. The after effects often include fatigue, speech problems, trouble maintaining weight, thyroid issues, swallowing difficulties, inability to swallow, memory loss, weakness, dizziness, high frequency hearing loss and sinus damage.
Survival rates for oral cancer depend on the precise site and the stage of the cancer at diagnosis. Overall, 2011 data from the SEER database shows that survival is around 57% at five years when all stages of initial diagnosis, all genders, all ethnicities, all age groups, and all treatment modalities are considered. Survival rates for stage 1 cancers are approximately 90%, hence the emphasis on early detection to increase survival outcome for patients. Similar survival rates are reported from other countries such as Germany.
Following treatment, rehabilitation may be necessary to improve movement, chewing, swallowing, and speech. Speech and language pathologists may be involved at this stage.
Chemotherapy is useful in oral cancers when used in combination with other treatment modalities such as radiation therapy. It is not used alone as a monotherapy. When a cure is unlikely, it can also be used to extend life and can be considered palliative but not curative care. Biological agents such as Cetuximab have recently been shown to be effective in the treatment of squamous cell head and neck cancers, and are likely to have an increasing role in the future management of this condition when used in conjunction with other established treatment modalities.
Treatment of oral cancer will usually be by a multidisciplinary team, with treatment professionals from the realms of radiation, surgery, chemotherapy, nutrition, dentistry, and even psychology all possibly involved with diagnosis, treatment, rehabilitation, and patient care.
Identifying and treatment the underlying malignancy constitutes an uptime approach. Topical 5-fluorouracil may occasionally be help, as may oral retinoids, topical steroids, vitamin A acid, urea, salicylic acid, podophyllotoxin, and cryodestruction employing liquid.
Chemotherapy in throat cancer is not generally used to "cure" the cancer as such. Instead, it is used to provide an inhospitable environment for metastases so that they will not establish in other parts of the body. Typical chemotherapy agents are a combination of paclitaxel and carboplatin. Cetuximab is also used in the treatment of throat cancer.
Docetaxel-based chemotherapy has shown a very good response in locally advanced head and neck cancer. Docetaxel is the only taxane approved by US FDA for head and neck cancer, in combination with cisplatin and fluorouracil for the induction treatment of inoperable, locally advanced squamous cell carcinoma of the head and neck.
While not specifically a chemotherapy, amifostine is often administered intravenously by a chemotherapy clinic prior to IMRT radiotherapy sessions. Amifostine protects the gums and salivary glands from the effects of radiation.
Radiation therapy is the most common form of treatment. There are different forms of radiation therapy, including 3D conformal radiation therapy, intensity-modulated radiation therapy, particle beam therapy and brachytherapy, which are commonly used in the treatments of cancers of the head and neck. Most people with head and neck cancer who are treated in the United States and Europe are treated with intensity-modulated radiation therapy using high energy photons. At higher doses, head and neck radiation is associated with thyroid dysfunction and pituitary axis dysfunction.
Nasopharyngeal carcinoma can be treated by surgery, by chemotherapy, or by radiotherapy. The expression of EBV latent proteins within undifferentiated nasopharyngeal carcinoma can be potentially exploited for immune-based therapies.
Improvement usually parallels that of the cancer, whether surgical or chemotherapeutic. Generalization of the associated visceral malignancy may worsen the eruption.
10 to 20% of patients treated for anal cancer will develop distant metastatic disease following treatment. Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy. Radiation is also employed to palliate specific locations of disease that may be causing symptoms. Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine. JD Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU. Median survival rates for patients with distant metastases ranges from 8 to 34 months.
Many different topical and systemic medications have been studied, including anti-inflammatories, antimycotics (target Candida species), carotenoids (precursors to vitamin A, e.g. beta carotene), retinoids (drugs similar to vitamin A), and cytotoxics, but none have evidence that they prevent malignant transformation in an area of leukoplakia.Vitamins C and E have also been studied with regards a therapy for leukoplakia. Some of this research is carried out based upon the hypothesis that antioxidant nutrients, vitamins and cell growth suppressor proteins (e.g. p53) are antagonistic to oncogenesis. High doses of retinoids may cause toxic effects. Other treatments that have been studied include photodynamic therapy.
The US Preventive Services Task Force (USPSTF) in 2013 stated evidence was insufficient to determine the balance of benefits and harms of screening for oral cancer in adults without symptoms by primary care providers. The American Academy of Family Physicians comes to similar conclusions while the American Cancer Society recommends that adults over 20 years who have periodic health examinations should have the oral cavity examined for cancer. The American Dental Association recommends that providers remain alert for signs of cancer during routine examinations.
There are a variety of screening devices, however, there is no evidence that routine use of these devices in general dental practice is helpful. However, there are compelling reasons to be concerned about the risk of harm this device may cause if routinely used in general practice. Such harms include false positives, unnecessary surgical biopsies and a financial burden on the patient.
Surgical removal of the lesion is the first choice of treatment for many clinicians. However, the efficacy of this treatment modality cannot be assessed due to insufficient available evidence. This can be carried out by traditional surgical excision with a scalpel, with lasers, or with eletrocautery or cryotherapy. Often if biopsy demonstrates moderate or severe dysplasia then the decision to excise them is taken more readily. Sometimes white patches are too large to remove completely and instead they are monitored closely. Even if the lesion is completely removed, long term review is still usually indicated since leukoplakia can recur, especially if predisposing factors such as smoking are not stopped.
Localised disease (carcinoma-in-situ) and the precursor condition, anal intraepithelial neoplasia (anal dysplasia or AIN) can be ablated with minimally invasive methods such as Infrared Photocoagulation.
Previously, anal cancer was treated with surgery, and in early-stage disease (i.e., localised cancer of the anus without metastasis to the inguinal lymph nodes), surgery is often curative. The difficulty with surgery has been the necessity of removing the internal and external anal sphincter, with concomitant fecal incontinence. For this reason, many patients with anal cancer have required permanent colostomies.
Current gold-standard therapy is chemotherapy and radiation treatment to reduce the necessity of debilitating surgery. This "combined modality" approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment. Survival and cure rates are excellent, and many patients are left with a functional sphincter. Some patients have fecal incontinence after combined chemotherapy and radiation. Biopsies to document disease regression after chemotherapy and radiation were commonly advised, but are not as frequent any longer. Current chemotherapy consists of continuous infusion 5-FU over four days with bolus mitomycin given concurrently with radiation. 5-FU and cisplatin are recommended for metastatic anal cancer.
As with the radiotherapy data, most of the available knowledge on the efficacy of chemotherapy derives from the treatment of advanced head and neck cancer rather than specific studies of HPV+OPC. Since 1976, many clinical studies have compared CRT to RT alone in the primary management of locally advanced head and neck cancers and have demonstrated an advantage to CRT in both survival and locoregional control. Cisplatin is considered the standard agent, and a survival advantage was seen for those patients who received radiation with concurrent cisplatin. Despite this no trials directly comparing cisplatin with other agents in this context have been conducted. The other agent that is widely used is Cetuximab, a monoclonal antibody directed at the epidermal growth factor receptor (EGFR). A 10% survival advantage at three years was noted when cetuximab was given concurrently with radiation (bioradiation). Cetuximab trials were completed prior to knowledge of HPV status. The main toxicity is an acneiform rash, but it has not been compared directly to cisplatin in HPV+OPC, although RTOG 1016 is addressing this question. Concurrent chemotherapy is also superior to chemotherapy alone (induction chemotherapy) followed by radiation. Cetuximab shows no advantage when added to cisplatin in combination with radiation. Although chemoradiation became a treatment standard based on clinical trials and in particular, meta-analyses, a subsequent population based study of patients with OPC, indicated no advantage to the addition of chemotherapy to radiation in either HPV+OPC or HPV-OPC, and significant concerns about added toxicity.
Chemotherapy also has a role, combined with radiation, in the postoperative setting (adjuvant therapy). Generally it is used where the pathology of the resected specimen indicates features associated with high risk of locoregional recurrence (e.g. extracapsular extension through involved lymph nodes or very close margins). It has shown improved disease-free survival and locoregional control in two very similar clinical trials in such high risk patients, EORTC 22931 (1994–2000) and RTOG 9501 (1995–2000). However, for HPV+OPC patients, such extracapsular spread does not appear to be an adverse factor and the addition of chemotherapy to radiation in this group provided no further advantage. Since the sample size to detect a survival advantage is large, given the small number of events in this group, these studies may have been underpowered and the question of the utility of adding chemotherapy is being addressed in a randomized clinical trial (ADEPT) with two year locoregional control and disease free survival as the endpoint. The addition of chemotherapy to radiation increases acute and late toxicity. In the GORTEC trial, chemotherapy with docetaxel provided improved survival and locoregional control in locally advanced OPC, but was associated with increased mucositis and need for feeding by gastrostomy. Chemotherapy and radiation are associated with a risk of death of 3–4% in this context. It is unclear whether the added toxicity of adding chemotherapy to radiation is offset by significant clinical benefit in disease control and survival.
It is thought that HPV+OPC patients benefit better from radiotherapy and concurrent cetuximab treatment than HPV-OPC patients receiving the same treatment, and that radiation and cisplatin induce an immune response against an antigenic tumour which enhances their effect on the cancer cells. Although the incidence of HPV positivity is low (10–20%), an advantage for HPV+OPC was seen in trials of both cetuximab and panitumumab, a similar anti-EGFR agent, but not a consistent interaction with treatment, although HPV+OPC appears not to benefit to the same extent as HPV-OPC to second line anti-EGFR therapy, possibly due to lower EGFR expression in HPV+OPC.
Concerns over the morbidity associated with traditional open surgical en-bloc resection, led to exploring alternative approaches using radiation. Intensity modulated radiation therapy (IMRT) can provide good control of primary tumours while preserving excellent control rates, with reduced toxicity to salivary and pharyngeal structures relative to earlier technology. HPV+OPC has shown increased sensitivity to radiation with more rapid regression, compared to HPV-OPC. IMRT has a two-year disease free survival between 82 and 90%, and a two-year disease specific survival up to 97% for stage I and II.
Reported toxicities include dry mouth (xerostomia) from salivary gland damage, 18% (grade 2); difficulty swallowing (dysphagia) from damage to the constrictor muscles, larynx and oesophageal sphincter, 15% (grade 2); subclinical aspiration up to 50% (reported incidence of aspiration pneumonia approximately 14%); hypothyroidism 28–38% at three years (may be up to 55% depending on amount of the thyroid gland exposed to over 45 Gy radiation; esophageal stenosis 5%; osteonecrosis of the mandible 2.5%; and need for a gastrostomy tube to be placed at some point during or up to one year after treatment 4% (up to 16% with longer follow up). Concerns have been expressed regarding excessive short and long term toxicity, especially dysphagia and xerostomia, and hence whether standard doses expose patients with better prognoses are being exposed to overtreatment and unnecessary side effects.
Biopsy screening although necessary is not mandatory most dentist can visually examine the area and proceed with the proper course of treatment.
Treatment includes:
- Abstention from chewing areca nut (also known as betel nut) and tobacco
- Minimizing consumption of spicy foods, including chiles
- Maintaining proper oral hygiene
- Supplementing the diet with foods rich in vitamins A, B complex, and C and iron
- Forgoing hot fluids like tea, coffee
- Forgoing alcohol
- Employing a dental surgeon to round off sharp teeth and extract third molars
Treatment also includes following:
- The prescription of chewable pellets of hydrocortisone (Efcorlin); one pellet to be chewed every three to four hours for three to four weeks
- 0.5 ml intralesional injection Hyaluronidase 1500 IU mixed in 1 ml of Lignocaine into each buccal mucosa once a week for 4 weeks or more as per condition
- 0.5 ml intralesional injection of Hyaluronidase 1500 IU and 0.5 ml of injection Hydrocortisone acetate 25 mg/ml in each buccal mucosa once a week alternatively for 4 weeks or more as per condition
- Submucosal injections of hydrocortisone 100 mg once or twice daily depending upon the severity of the disease for two to three weeks
- Submucosal injections of human chorionic gonadotrophins (Placentrax) 2-3 ml per sitting twice or thrice in a week for three to four weeks
- Surgical treatment is recommended in cases of progressive fibrosis when interincisor distance becomes less than . (Multiple release incisions deep to mucosa, submucosa and fibrotic tissue and suturing the gap or dehiscence so created by mucosal graft obtained from tongue and Z-plasty. In this procedure multiple deep z-shaped incisions are made into fibrotic tissue and then sutured in a straighter fashion.)
- Pentoxifylline (Trental), a methylxanthine derivative that has vasodilating properties and increases mucosal vascularity, is also recommended as an adjunct therapy in the routine management of oral submucous fibrosis.
- IFN-gamma is antifibrotic cytokine which alters collagen synthesis and helps in OSF.
- Colchicine tablets 0.5 mg twice a day
- Lycopene, 16 mg a day helps in improvement of OSF
The treatment of patients with oral submucous fibrosis depends on the degree of clinical involvement. If the disease is detected at a very early stage, cessation of the habit is sufficient. Most patients with oral submucous fibrosis present with moderate-to-severe disease. Severe oral submucous fibrosis is irreversible. Moderate oral submucous fibrosis is reversible with cessation of habit and mouth opening exercise. Current modern day medical treatments can make the mouth opening to normal minimum levels of 30 mm mouth opening with proper treatment.
Resection of the polyps is required only if serious bleeding or intussusception occurs. Enterotomy is performed for removing large, single nodules. Short lengths of heavily involved intestinal segments can be resected. Colonoscopy can be used to snare the polyps if they are within reach.
Adjuvant chemotherapy is a recent innovation, consisting of some combination of paclitaxel (or other taxanes like docetaxel), doxorubicin (and other anthracyclines), and platins (particularly cisplatin and carboplatin). Adjuvant chemotherapy has been found to increase survival in stage III and IV cancer more than added radiotherapy. Mutations in mismatch repair genes, like those found in Lynch syndrome, can lead to resistance against platins, meaning that chemotherapy with platins is ineffective in people with these mutations. Side effects of chemotherapy are common. These include hair loss, low neutrophil levels in the blood, and gastrointestinal problems.
In cases where surgery is not indicated, palliative chemotherapy is an option; higher-dose chemotherapy is associated with longer survival. Palliative chemotherapy, particularly using capecitabine and gemcitabine, is also often used to treat recurrent endometrial cancer.
When the appearance is caused by heat, the lesion is usually completely reversible within a few weeks if the smoking habit is stopped. This is the case even if the condition has been present for decades. Without stopping smoking, spontaneous remission of the lesion is unlikely. If the lesion persists despite stopping smoking, this is usually then considered to be a true leukoplakia rather than a reactionary keratotis, and may trigger the decision to carry out a biopsy to confirm the diagnosis. Since this condition almost always develops in the setting of long term heavy smoking, it usually indicates the need for regular observation for cancers associated with smoking, e.g. lung cancer.
There are a number of possible additional therapies. Surgery can be followed by radiation therapy and/or chemotherapy in cases of high-risk or high-grade cancers. This is called adjuvant therapy.
This form of cancer is often seen in those who chew tobacco or use snuff orally, so much so that it is sometimes referred to as "Snuff dipper's cancer." Chewing betel nuts is an additional risk factor commonly seen in Taiwan.
Apart from stopping the habit, no other treatment is indicated. Long term follow-up is usually carried out. Some recommend biopsy if the lesions persists more than 6 weeks after giving up smokeless tobacco use, or if the lesion undergoes a change in appearance (e.g. ulceration, thickening, color changes, especially to speckled white and red or entirely red). Surgical excision may be carried out if the lesion does not resolve.
Treatment of mucositis is mainly supportive. Oral hygiene is the mainstay of treatment; patients are encouraged to clean their mouth every four hours and at bedtime, more often if the mucositis becomes worse.
Water-soluble jellies can be used to lubricate the mouth. Salt mouthwash can soothe the pain and keep food particles clear so as to avoid infection. Patients are also encouraged to drink plenty of liquids, at least three liters a day, and avoid alcohol. Citrus fruits, alcohol, and foods that are hot are all known to aggravate mucositis lesions. Medicinal mouthwashes may be used such as Chlorhexidine gluconate and viscous Lidocaine for relief of pain. Palifermin is a human KGF (keratinocyte growth factor) that has shown to enhance epithelial cell proliferation, differentiation, and migration. Experimental therapies have been reported, including the use of cytokines and other modifiers of inflammation (e.g., IL-1, IL-11, TGF-beta3), amino acid supplementation (e.g., glutamine), vitamins, colony-stimulating factors, cryotherapy, and laser therapy.
Symptomatic relief of the pain of oral mucositis may be provided by barrier protection agents such as concentrated oral gel products (e.g. Gelclair). Caphosol is a mouth rinse which has been shown to prevent and treat oral mucositis caused by radiation and high-dose chemotherapy. MuGard is a FDA-cleared mucoadhesive oral protectant, developed by Access Pharmaceuticals, Inc., that is designed to form a protective hydrogel coating over the oral mucosa while a patient is undergoing chemotherapy and/or radiotherapy cancer treatments to the head and neck. Additionally, the efficacy of MuGard for the prevention or treatment of mucositis has been tested by a prospective, randomized clinical trial in which 43% of head and neck cancer patients using MuGard prophylactically never got oral mucositis.
NeutraSal is an FDA-cleared calcium phosphate mouth rinse which has been shown in an open-label, observational registry trial to prevent and reduce the severity of oral mucositis caused by radiation and high-dose chemotherapy. In the trial, 56% of the radiotherapy patients reported 0 (WHO score) or no mucositis, which is significantly lower than historical rates. Another super saturated calcium phosphate rinse on the market and cleared by the FDA is the US based SalivaMAX. The Mayo Clinic has been testing the antidepressant doxepin in a mouthwash to help treat symptoms.
In 2011, the FDA cleared episil oral liquid for the management and relief of pain of oral lesions with various etiologies, including oral mucositis/stomatitis which may be caused by chemotherapy or radiation therapy. The transformative mechanism of action of episil creates a lipid membrane that mechanically bonds to the oral cavity mucosa to coat and soothe inflammation and ulcerations, and blanket painful lesions. In a multicenter, randomized, double-blind, single-dose study involving 38 head and neck cancer patients with oral mucositis (WHO grades 2-3) undergoing radiation therapy, episil clinically demonstrated fast-acting relief that lasted up to 8 hours. Episil oral liquid is marketed in the US by Cangene.
In a 2012 randomized controlled pilot study involving pediatric patients, topical application of honey was found to reduce recovery time compared to benzocaine gel in grade 2 and 3 chemotherapy-induced oral mucositis to a degree that was statistically significant. In grade 3 oral mucositis, honey was as effective as a mixture of honey, olive oil and propolis, while both treatments were found to reduce recovery time compared to the benzocaine control.
Clinical research is ongoing in oral mucositis. A recent phase 2 exploratory trial in oral mucositis reported that dusquetide, a unique innate immune modulator with a mechanism that potentially addresses each of the phases of OM pathophysiology, is able to reduce the duration of severe oral mucositis, as well as reducing the incidence of infections. Dusquetide is being developed by Soligenix, Inc.
Physically ablative methods are more likely to be effective on keratinized warts. They are also most appropriate for patients with fewer numbers of relatively smaller warts.
- Simple excision, such as with scissors under local anesthesia, is highly effective.
- Liquid nitrogen cryosurgery is usually performed in an office visit, at weekly intervals. It is effective, inexpensive, safe for pregnancy, and does not usually cause scarring.
- Electrocauterization (sometimes called "loop electrical excision procedure" or LEEP) is procedure with a longer history of use, and is considered effective.
- Laser ablation has less evidence to suggest its use. It may be less effective than other ablative methods. It is extremely expensive, and often used as a last resort.
- Formal surgical procedures, performed by a specialist under general anesthesia, may be necessary for larger or more extensive warts, intra-anal warts, or warts in children. It carries a greater risk of scarring than other methods.