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Oral cancer Dr. Hani Al Sheikh Radhi 2016 Oncogenesis (Carcinogenesis): Progression from normal (healthy) cell to premalignant or potentially malignant cell. The process involves series of genetic steps; abnormal function of molecules regulating cell signaling, growth, survival, angiogenesis and cell cycle control, over expression of oncogene and shutting down of tumor suppressor genes. Malignant transformation is a complicated process to be understood you must learn a few terms first. Dysplasia: Term used in pathology to refer to abnormalities of cell development. Increase number of immature cells and decrease the number of mature cells [include: cells of unequal size, abnormal shaped cells, hyper-chromatism (condition where part of the cell especially cell nuclei stain more intensely than normal), increased number of cells which are currently dividing]. According to the severity of the previously mentioned features dysplasia can be classified into mild, moderate, and severe. Carcinoma in situ: The cells lost maturation and almost all the malignant changes occurred (the tissue lost the original identity) but the cells are still contained within the basement membrane; when these cells start the invasion beyond the basement membrane and start invading the adjacent tissue it will change into invasive carcinoma. Apoptosis: programmed cell death. Angiogenesis: Growth of new blood vessels from pre-existing vessels. This mechanism will provide nutrition for the growing mass. Metastases: Spread of tumor cells into different parts of the body. It is the process which is often the most life threatening in cancer. Mutation: Changing the structure of a gene which cause an alteration in the genetic map of the cell; which can lead to cancer. Oncology is the study and the science of new growths. Neoplasm refers to any new disease form of tissue growth. Cancer is the overall name applied to malignant growths. Cancer development is a process of mutation within the cellular DNA influenced by many risk factors. What is cancer? Normal growth controlled by a fine balance between growth promoting and growth inhibition, this mechanism is controlled by specific signals. When the body requires new cell division (for example in wound healing) it will direct these signals in the specific region, which required growth to stimulate or to initiate the cells to proliferate. Oral cancer Dr. Hani Al Sheikh Radhi 2016 In tumor this mechanism is defected and there will be Continuous cell proliferation; tumor cell will initiate its own proliferating signals independently from the body control. The cell is no longer differentiated (it will be different from the surrounding original tissue), and There will be shut down of the programmed cell death mechanism (apoptosis). Cancer arises from a single cell, [the whole tumor originate from one cell]. “Cancer is an abnormal growth of cells caused by multiple changes in gene expression leading to a dysregulated balance of cell proliferation and cell death and ultimately evolving into a population of cells that can invade tissues and metastasize to distant sites, causing significant morbidity and, if untreated, death of the host” Features of malignant tumors: cells no longer depend on body control. 1- Normal cells will grow in mono-layer while cancer cells are able to grow into multi-layers over and below each other). 2- Cancer cells are less adherent than normal cells. 3- Normal cells stop proliferation when they reach a certain size (mass) while tumor cells keep proliferating. Common related oral premalignant lesions If a cancer can be detected early, before it has acquired all of the mutations necessary for invasion and metastasis it may be possible to successfully treat the disease locally. It has been observed that certain oral lesions, specifically leukoplakias and erythroleukoplakias, have the potential for malignant transformation. “Not all oral squamous cell carcinoma are preceded by leukoplakias, not all leukoplakias progress to oral cancer” 1Leukoplakia: according to the WHO (World Health Organization) leukoplakia is defined as “white patch or plaque that cannot be characterized clinically or pathologically as any other disease”. It is diagnosed by exclusion [before the clinician inform the patient that he/she has leukoplakia he must exclude other causes such as frictional keratosis, candidiasis, leukoedema, lichen palnus]. Malignant transformation rate of oral leukoplakia range between 3-6%. Floor of the mouth is the highest risk site [leukoplakia discovered in this site usually demonstrate severe dysplasia, carcinoma in situ, or invasive carcinoma]. Other high risk sites with leukoplakia are the tongue and lips. the clinical presentation can be associated with how serious the leukoplakia. Main clinical presentations include: Thin homogenous leukoplakia Thick leukoplakia Oral cancer 2016 Verrucous Leukoplakia: papillary exophytic projections. Speckled Leukoplakia: Mixed Red and white lesion. The risk from high to low, speckled, verrucous, thick and the least serious thin leukoplakia [that doesn’t mean thin leukoplakia cannot be sinister]. Speckled Leukoplakia ; this is the worst type of leukoplakia which is speckled and the worst site which is floor of the mouth Thick leukoplakia extending from the lateral borders of the tongue to the floor of the mouth, Dr. Hani Al Sheikh Radhi Thin Homogenous Leukoplakia, consider the least sinister type of leukoplakia Verrucous Leukoplakia, in this case it was diagnosed as invasive carcinoma. Management of Leukoplakia Exclude any other conditions. Establish Leukoplakia. Identify the degree of dysplasia or malignancy by doing a biopsy and histopathological examination. Oral cancer Dr. Hani Al Sheikh Radhi 2016 The management will depend on the degree of dysplasia, the site, and the clinical appearance. Lesions exhibit carcinoma in situ or early invasive carcinoma must be excised with normal margins to allow better histopathological investigation. Lesions with low to moderate dysplasia in high risk sites (floor of the mouth, tongue) and lesions with severe dysplasia at low risk sites are the most debatable. Shall we excise with margin? Or just excise the lesion by itself? That answer will depend on the surgeon’s clinical decision, by estimating how serious the condition and according to the surgeon experience. Treatment options Surgical excision, cryosurgery, CO2 Laser, systemic and local application of vitamins and other medications. Surgical Excision: Traditional method Recurrence rate 15-30%, usually recurrence noted adjacent to the excised lesions, especially at high risk sites. One of the problems includes inability to excise widespread or diffuse lesions without causing morbidity and esthetic problems. Cryosurgery: destroy and remove soft tissue by therapeutic freezing. Liquid nitrogen is the most commonly used material in cryosurgery. Main disadvantages are lack of depth control [we cannot know how much we can remove from the tissue], the other problem will that cryosurgery will destroy the tissue so we cannot have a proper biopsy to detect the lesion, Nowadays replaced by CO2 laser. CO2 Laser: Can be used either to evaporate the entire lesion [not recommended because we will not have enough tissue for examination], the other is to excise the lesion and it can provide tissue sample. CO2 laser has the advantage of obtaining biopsy (specimen) with less morbidity than scalpel technique and provide adequate hemostasis especially when we excise large lesions. Healing is better with CO2 laser than scalpel. The only drawback of CO2 laser is that the specimen margins may be cauterized and therefor lateral spread of dysplasia or malignancy cannot be assessed. Nonsurgical Therapies: Vitamin A, Retinoid, Vitamin E, and Bleomycin (glycopeptide antibiotic, destroy DNA used in treatment of Hodgkin’s lymphoma, squamous cell carcinoma. 2Erythroplakia: a premalignant considered uncommon compared leukoplakia. Appears mainly on soft palate, buccal mucosa, and floor of the mouth. WHO definition “ the term erythroplakia is used analogously to leukoplakia to designate lesions of the oral mucosa that present as red areas and cannot diagnosed as any other definable lesion”. Almost all erythroplakias demonstrate epithelial dysplasia, carcinoma in situ, invasive carcinoma. Erythroplakia is diagnosed by exclusion and biopsy, conditions that may resemble eythroplakia can include candidal infections, histoplasmosis, TB, lichen planus, systemic lupus erythromatosis, pemphigus, pemphigoid, hemangioma, Kaposi sarcoma….etc. Oral squamous mucosal lesions appear red why? Due to atrophy of the mucosa and dilation of sub-epithelial capillaries. Erythroplakia can appear smooth, granular, and nodular, with well-defined margins. Erythroplakia has the highest risk of malignant transformation compared to all other premalignant and potentially malignant oral mucosal lesions. Oral cancer Dr. Hani Al Sheikh Radhi 2016 Management Because of the high incidence of significant epithelial dysplasia, carcinoma in situ or early invasive carcinoma at the time of diagnosis. Surgical intervention is necessary, complete excision of the lesion with clear margins down to the submucosal level. This will provide good specimen for investigation and decrease risk of recurrence. General management protocol for suspected premalignant conditions (1) Eliminate risk factors- tobacco,alcohol (2) Clinical photographic records. (3) Base line haematology- full blood count,serum ferritin, B12, folate (4) Candidal swab (5) Incisional biopsy and dysplasia characterization. (6) Careful clinical follow-up and consider repeat biopsy for mild dysplasias (7) Laser excision for moderate/severe dysplasias. (8) Long-term clinical follow up (9) Monitor oral mucosa for field changes. Cancer Risk Factors Cancer is a multifactorial condition. DNA mutation occurs spontaneously, especially via damage by oxidation or free radicals. The rate of DNA mutation increases by various cancer risk factors. Life style Factors: Tobacco, Alcohol, and Betel quid chewing (it is a combination of certain plants that used in India). This risk factor is usually age related (i.e. people age 50 and more), because the effect is accumulative depending on how long the patient had been exposed to the previous factors. Younger age groups are being more involved nowadays may be due to associating of other factors. [viruses such as Human Pailloma Virus & Epistin Barr Virus can induce early malignancy]. Tobacco generates carcinogen [cancer causing chemicals], such as TSNAs (Tobacco specific nitrosamines) they destroy anti-oxidant enzymes. Alcohol carcinogenesis process: alcohol metabolized by certain enzymes into “Acetaldehyde” which is a carcinogen. Oral cancer Dr. Hani Al Sheikh Radhi 2016 Tobacco and alcohol have synergistic effect (each one increase the carcinogenesis properties of the other). Virus Infection: Human papilloma virus (HPV): More than 100 types of human papilloma virus are known. HPV-16 & HPV-18 have been the most common types associated with oral cancer. It is less associated with alcohol and smoking but more related to marijuana and oral sex. Generally they have better prognosis than cancer associated with smoking and alcohol. Herpes virus: Herpes simplex virus nucleic acid had been extracted from oral cancer, and herpes simplex associated cancer is usually associated with smoking. Dietary Factors: Eating fruits and vegetables is believed to reduce the risk of oral cancer. Studies have shown that Mediterranean (Especially Greece and Italy) diet particularly associated with reduced cancer risk. The main components of their diet [fresh fruits and vegetables, reduced red meat, white meat and fish being a major component, increased consumption of unprocessed olive oil, and increased consumption of dietary fibers]. The whole idea of diet is to increase the anti-oxidants level within the body, to decrease the oxidation risk of DNA. Social and Economic status: Deprived people from low socio-economic class is associated with increased risk of oral cancer. That can be due to the bad living environment, stressful life; they have much bad lifestyle factors, and a bad diet. Environment: Ionizing radiation from natural or therapeutic sources or nuclear accident (such as Chernobyl accident or Iraq war) may contribute to oral cancer. Occupation: Workers in leather and metal producing factories without taking the proper precautions can be a risk. Genetic Factors: Inheritance of oral cancer specifically and Cancer generally extremely low and may contribute to no more than 1-3% of cancer. Anatomical Knowledge in Cervical lymph nodes Cervical Lymph Node Levels: Before we start discussing how to manage oral cancer you need to have a knowledge about the lymph nodes that drain the oral cavity; lymphatic drainage through lymph nodes within the neck considered the main route of metastases. The lymphatic system of the neck is divided into three systems: Waldeyer’s internal ring. This ring includes the adenoids, the tubal and lingual tonsils, the palatine tonsils and aggregates of the lymphoid tissue on the posterior pharyngeal wall. Tumors from this area have a high tendency for lymphatic spread. Waldeyer’s external ring. This set of nodes mainly drains the superficial tissues of the head and neck. In the head, the nodes are mainly located around the skull base and are the occipital, postauricular, parotid and buccal nodes. In the neck, the main nodes completing the Waldeyer’s external ring are the superficial cervical, submandibular, submental and anterior cervical nodes. These nodes drain tissues from the scalp, eyelids, face, nasal sinuses and oral cavity. Oral cancer Dr. Hani Al Sheikh Radhi 2016 The deep lymph node system. This consists of the upper, middle and lower cervical nodal groups that are situated along the internal jugular vein, the spinal accessory group that accompanies the XI nerve in the posterior triangle, and the nodes in the midline of the neck. Neck is divided into six surgical levels based on anatomical structure area. The head and neck area drains into more than 300 nodes within the neck. Understanding levels will help clinicians to tailor the proper treatment plan. Level I: Include submental and submandibular lymph nodes. Level II: Upper jugular lymph nodes surrounding jugular vein and adjacent spinal accessory nerve. Level III: Middle jugular lymph nodes surrounding internal jugular vein. Level IV: Lower jugular lymph nodes. Level V: All the nodes in the posterior triangle, posterior to the sternocleidomastoid muscle. Level VI: Anterior triangle includes pretracheal, paratracheal, prelaryngeal lymph nodes. These are the surgical Levels of the Neck, Notice that almost each level is subdivided into A & B, to cover precisely the anatomical relation of the nodes with their source of drainage. These are the anatomical triangles of the neck, which can be less helpful during surgery. Physical Examination of Oral Squamous cell carcinoma Complete evaluation of the head and neck. Thorough examination of the oral cavity. Size, appearance, texture, colour, fixation to bone and adjacent structures. Inspection and palpation of all mucosal surfaces. Cranial nerves examination [specifically V, VII, X, XI, and XII]. o Explore tongue mobility for hypoglossal nerve. Oral cancer Dr. Hani Al Sheikh Radhi 2016 o Facial nerve and spinal accessory must be evaluated because these structures can be involved by Oral Squamous Cell Carcinoma. Area of erythroplakia, leukoplakia, ulcerations, and masses especially fixed or firm masses. Palpation of the neck is critical because of the cervical nodal metastases is the single most reliable prognostic factor in patients with Oral SCC. Check number, size, and site of the involved lymph nodes. Early stage oral cancer usually involves level I, II, and III. In patient with cervical metastases at the time of the diagnosis 5 year survival rate is reduced by 50%. Cervical node metastases are noted in about 30% of patients who have Oral SCC. Presence of trismus can indicate pterygomaxillary space involvement. Decreased mobility of the tongue can be a sign of involvement of tongue deep muscles. Perineural invasion [tumor invades nerves and sometimes metastases occur through nerve fibers] can occur in 27-53% of patients with Oral SCC. Evaluated by checking sensation of the cheeks, lips, chin, palate, and alveolar gingivae. Accurate measurements of primary lesion before biopsy is very important because that will help the surgeon to determine the T stage: tumor size (will be discussed later), other important factor edema post biopsy can alter the true size of the tumor. Complete evaluation of all anatomical locations within the oral cavity must be performed by visual examination and palpation to detect any mucosal abnormalities. Examination of the oral cavity: remove all dental appliances, use of dental mirror for indirect evaluation of nasopharynx and hypopharynx. Bimanual palpation to assess any involvement of structures such as deep muscles of the tongue, floor of the mouth, buccal mucosa, salivary structures, or bony mandibular structures. Assessment of the lateral tongue done by anterior and lateral traction of the tongue with cotton gauze. Radiographic Examination and Evaluation Evaluation of deep tissue involvement and the presence of positive cervical lymphadenopathy will require several imaging modalities to assess the depth of involvement, spread, and estimate the CLINICAL Margins. Plain Radiograph: OPG (ORTHOPANTOMOGRAM): To establish jaw bone or teeth involvement. Chest x-ray: Screening for bronchial caner or metastatic lung cancer. Occipitomental View (OM): Assess maxillary sinus or orbital involvement. Occlusal and periapical view: Augment the OPG for better screening Plain films are not useful for routine screening because they fail to show early cortical involvement. CT scan: CT scans alone or usually with intravenous contrast (iodine based) are the most common imaging modality. CT scan is very good in demonstrating hard tissue structures; however, MRI is a Oral cancer Dr. Hani Al Sheikh Radhi 2016 better investigation modality for soft tissue involvement. MRI: Superior in defining soft tissue details. Ultrasound: Ultrasound has limited success in the evaluation of oral cancer, but it can easily evaluate neck masses and nodal involvement. Ultrasound has the advantage of being available and inexpensive made it a good diagnostic tool for examining tneck involvement before obtaining more advanced imaging of the neck. PET Scan (Positron emission tomography): It is a form of nuclear medicine that has been used to differentiate between malignant disease recurrent tumor and to identify nodal metastasis. FDGPET: [FDG (Fluro-Deoxy Glucose)] is the most commonly used form of PET scans, depends on the difference of metabolism of this type of glucose between normal and malignant tissue. [Malignant tissue and cells uptake (consume) of FDG is much greater than normal cells] the PET will examine the areas within the body that will show higher uptake rate, which will suggest tumor. The main draw backs of PET that it is expensive and it doesn’t shows anatomical landmarks; so new machines developed which correlate CT scans with PET scan, the CT will give the anatomical landmarks while the PET will examine the area for tumor involvement, the new machine had been named CT/FDGPET. Diagnostic Methods A variety of approaches have been used to obtain diagnostic tissue samples of suspicious oral lesions, and several are discussed in this lecture. Despite the growing number of adjuncts available to assist in the clinical evaluation of lesions with uncertain biologic potential, surgical biopsy remains by far the most popular means of obtaining a final tissue diagnosis. Punch Biopsy: A punch biopsy is a soft tissue sampling instrument having a circular cutting edge of varying diameter. It is most frequently used by dermatologists to sample skin lesions but can be used on mucosal surfaces as well. For study purposes, an advantage of the punch instrument is its ability to provide reproducibly sized epithelial samples of lesion or control tissues. Oral cancer Dr. Hani Al Sheikh Radhi 2016 Punch biopsy technique, rarely used in oral cavity, it can be used when we want to have multiple biopsies within the same size especially for researches and studies. Scalpel Biopsy (Gold standard): is the most commonly and most successful used method. We have two types either Excisional (remove the whole lesion) or Incisional (remove part of the lesion). Excisional biopsy is most often reserved for clinically benign or, at worst, precancerous mucosal lesions that are less than 2 cm in diameter. Most suspicious lesions of the oral cavity are diagnosed through an incisional biopsy, where a portion of the abnormal surface tissue is removed for histopathologic interpretation. The desirable and undesirable biopsies. The desirable although narrow but it is deep, containing part of the normal tissue. The upper incision is excisional biopsy including the whole lesion within the biopsy, while below notice that we removed only part of the lesion with large part of the clinically normal tissue. Fine Needle Aspiration (FNA): Fine-needle aspiration (FNA) cytology is a valuable tool in the diagnosis of superficial masses of the head and neck region. Rarely helpful for oral cavity squamous cell carcinoma, it is best used for lesions with cystic cavities which allow aspiration of fluids and cells for cytology diagnosis. Oral cancer Dr. Hani Al Sheikh Radhi 2016 Diagnostic Adjuncts Cytology: Oral exfoliative cytology (remove superficial layer of cells) has been an adjunct to oral diagnosis. It has been primarily used to provide rapid and inexpensive identification of superficial infectious agents, such as fungi. It showed to be inefficient method in the diagnosis of malignant and pre-malignant lesions as we mentioned to obtain proper diagnosis, we need good amount of tissue, including normal tissue. Brush Biopsy (Brush Cytology): investigating persistent oral epithelial lesions not considered suspicious for carcinoma. Toluidine Blue: dye designed to stain acidic cellular components, such as DNA and RNA. Its use in the detection of precancerous/cancerous tissue is based on the fact that dysplastic tissue contains quantitatively more DNA and RNA than non-dysplastic tissue. TB staining may provide better demarcation of lesion margins, guide biopsy site selection, and is thought to be valuable in identification and visualization of lesions in high-risk patients. Drawbacks; the main drawback that it can give misdiagnosis in inflammation, hyperactive, and bengin hyperplasia. Optical Detection of oral cancer: optical technologies provide information on the physiologic condition of the tissue at a molecular level. Early research in optical diagnostics suggested Oral cancer Dr. Hani Al Sheikh Radhi that alterations in light-tissue interactions can be used to differentiate normal from malignant tissue. Oral Cancer Prognostic Factors & Treatment Options TNM staging: Staging method based on tumor size (T), Nodal status (N), and Metastases (M). Developed in 1950, and it is only applied to carcinoma. The TNM staging system is applied to various carcinomas each TNM has different evaluation of each anatomical site. Purpose of TNM staging Aid clinician in planning of treatment. Give some indication about prognosis. Assist in evaluation of treatment results. Facilitate the exchange of information between clinicians. The components of TNM usually assessed by physical examination and imaging techniques to delineate each of its components. 2016 Oral cancer Dr. Hani Al Sheikh Radhi 2016 Invasion of adjacent structures (Ex: T4a Invasion of larynx, intrinsic muscles of the tongue, medial pterygoid plate, hard palate, or mandible.) Histologic grading, tumor staging, and clinical behavior 1- Tumor size and staging: T refers to the primary lesion and is graded on greatest dimension and presence of adjacent tissue infiltration. N refers to regional lymph node involvement and is graded on the presence of nodes, greatest dimension, and side of involvement in relation to the primary tumor. M grades distant metastasis and is based simply on its presence (M1) or absence (M0). 2- tumor volume: can be done easily depending on CT and MRI scans, but the role of these measurements in prognosis requires further studying because sometimes we have small volume tumor but with aggressive biological behavior which may be related to bad prognosis, on the other hand we may have large exophytic growth, well differentiated which may shows good prognosis. Tumor thickness can be more helpful than diameter, however, until now defining tumor thickness between clinicians and pathologist is not established yet [some commented on tumor thickness post-surgery resected specimen, some depended on the maximum point of measurements, while others believe that the invasion front is more relevant to calculate tumor depth]. 3- Tumor behavior: tumor behavior can vary even within the same type of malignancy and especially with squamous cell carcinoma the behavior can vary. - Age of the patient: the younger the patient more agrressive tumor. - Gender: males are prone to more aggressive tumors. - Race: Africans and some tribes may have more aggressive tumors - Degree of differentiation: the less differentiated cells the more aggressive tumor. - Vascular and Perineural Invasion: Both parameters have been noted to be signs of aggressive tumor behavior. Those parameters can alter treatment options significantly especially for T1/T2 tumors, because when vascular and perinueral invasion present the prognosis will be very poor. 4- site of the tumor: Tongue tumors used to have the worst prognosis, but nowadays the outcomes are improving after the introduction of elective neck dissection [removal of lymph nodes in patients with N0]. Oral cancer 2016 Dr. Hani Al Sheikh Radhi Buccal sites now considered to have the worst prognosis. They usually have more aggressive biology with tendency for local recurrence, and that is exacerbated by involvement of stensons’s duct or muscular invasion. 5- Surgical Margins: Determining the surgical margin is a challenging procedure; the surgeon must cut into about 1.5 cm of healthy tissue during surgery to reduce the risk of recurrence and ensure removal of the clinical tumor. Unclear margin on histopathological examination post-resection considered as a poor prognostic sign and one of the criteria for post – operative radiotherapy. - Frozen Section Biopsy: is intra-operation biopsy. The surgeon will cut until he/she feels that they reach clear margin surgically, the biopsy will be sent for examination during the surgery to ensure that margins are not only clear surgically but histopathologically as well. Ablative Surgical Treatment for Malignant Tumors of the Oral Cavity Key Points • Most common malignant tumors of the oral cavity are Squamous Cell Carcinoma (SCC). • Treatments of oral cancer are multidisciplinary and consider the need for adjunctive therapy, reconstruction, and rehabilitation of the patient in addition to ablative surgery. • Surgical management of lesions inside the oral cavity is affected by the size and the location of the tumor. • Three dimensional excision with cuff of normal tissue at the peripheral and deep margins of the specimen. • Bone resection for invasion of the mandibular bone can be performed either by rim resection or by segmental resection. Rim resection is recommended when the depth of soft tissue invasion from pre-op scanning is less than 5mm. Segmental resection is necessary if extensive invasion of soft tissue is close to the mandible or within the mandible itself. A: Rim resection (marginal) mandibulectomy. B: Segmental Mandibulectomy. Surgical management of the neck varies according to the tumor stage. Treatment of N0 tumors is controversial. “WAIT-AND –SEE” strategy is more accepted in T1 tumor (depending on the site usually) than in large lesions. Thick T2 N0 of the tongue usually warrants the use of elective neck dissection (selective neck dissection). Neck Management We mentioned before that neck and nodal involvement can be the most important prognostic factor during the management of head and neck cancer. Oral cancer • 2016 Dr. Hani Al Sheikh Radhi 30-40% of patients presented with OSCC usually have nodal involvement. • Occult metastasis: Undetectable infiltration of tumor cells into the nodal lymphatic system. That cannot be diagnosed by our available conventional modalities. That opened the way for what is called N0-STAGE management by “elective neck dissection”. • Sentinel lymph node biopsy (SLN biopsy): It is a procedure developed in surgical oncology. The concept is based on the fact that the efferent lymphatic channels draining the primary tumor lead directly to the first (sentinel) lymph node in a regional chain. The sentinel lymph node is the most likely to include metastatic disease. When patient present with OSCC without any clinical involvement of lymph nodes the surgeon may decide to obtain (SLNB), by removing only the first most suspicious lymph node for histopathological assessment; if the result were negative (the node is not infiltrated with cancerous cells) this may suggest that the rest of the chain is clear and further surgery is indicated. Problems with SLNB, skipping of lymph nodes, lymphatics anatomy is not predictable. Lymph nodes drainage in relation to oral sites Different functional anatomy of lymphatic drainage from different oral sites; notice the complicated pattern of drainage which made it difficult to predict the exact pathway of drainage. Neck Dissection Classification of Neck Dissection 1- Radical Neck Dissection (RND): Include removal of all ipsilateral (on the same side of the tumor) cervical lymph nodes extending from the inferior borders of the mandible, to the clavicles including levels I – V. Including the removal of three important non-lymphatic structures: the internal jugular vein (IJV), Sternocleidomastoid SCM, and the spinal accessory nerve (SAN). Oral cancer Dr. Hani Al Sheikh Radhi 2016 2- Modified Radical Neck Dissection (MRND): Refers to removal of the same lymph nodes level I-V as the radical neck dissection but with preservation of (SAN), or (IJV), or (SCM). According to the preserved non-lymphatic structures (MRND) can be further subdivided into three types: TYPE I: Preserve the spinal accessory nerve (SAN) TYPE II: Preserve the (SAN) and the Sternocleidomastoid Muscle (SCM) Type III: Preserve the (SAN), (SCM), and the internal Jugular vein (IJV) with removal of only lymph nodes from level I-V. 3- Selective Neck Dissection (SND): Refers to the preservation of one or more lymph nodes group normally removed in (RND). The majority of oral cancer will primarly involve nodes from level I-III. SND used with oral cancer is named SND(I-III)[i.e. Selective neck dissection from level I to level III: previously known as supra-omohyoid selective neck dissection]. Nowadays it is recommended to include level IV when the cancer involves the tongue because about 16% of tongue tumors may skip into level IV, so SND (I-IV). 4- Extended Neck Dissection: Refers to removal of additional lymph node groups, or additional nonlymphatic structure or both, that is not normally included within the RND (for example; medistinal nodes or non-lymphatic structure such as carotid artery or hypoglossal nerve). In the presence of metastases in level (I) through (III) the risk of disease in level (IV) increases from 3% to 17% but the risk of level (V) involvement remains less than 3%, so it is logical to dissect only level (I) through (III) in oral cancer with clinically N0 neck and level (I) through (IV) if there is a clinically evident nodal disease in level (I) through (III). Radiotherapy post- surgery is recommended when neck stage is N2 or above, or when extracapsular spread (ECS) is present. Oral cancer Dr. Hani Al Sheikh Radhi 2016 SND not recommended in the presence of large lymph node, and SND is contraindicated when we have nodal fixation or large ECS and history of surgery and radiotherapy. The incidence of occult metastases in N0 neck, according to the distribution of the major nodal groups within the neck Access Surgery for Oral Cancer Maxillary Approaches 1- Weber-Fergusson Maxillectomy Incision 2- Mid-face degloving. 3- Posterior maxillary approach (Weber-Fergusson + Lip splitting Mandibulotomy) Mandibular Approaches 1- Transoral approach. 2- Lip Splitting Mandibulotomy 3- Pull through (transcervical approach) Radiation Cell death can be divided into two general types: 1- Reproductive cell death; which results from damage to the cellular genetic materials. 2- Apoptosis; programmed cell death. Radiation can cause either type and also slows cellular division. Aims of Radiotherapy Oral cancer Dr. Hani Al Sheikh Radhi 2016 Radical Radiotherapy: It is radiotherapy given at high doses with curative intent. The dose will be the highest delivered without functional consequences. That means avoiding catastrophic squeal (such as blindness) and limiting the incidence of major complications (such as osteoradionecrosis) to low levels, commonly around 5% or less, and limiting other conditions as far as possible (such as dryness of the mouth and problems with swallowing). For most epithelial tumors, higher doses result in better rate of local control but higher doses also create greater morbidity. Palliative Radiotherapy: control of symptoms in situations which canecr is incurable or the patient is not fit enough to withstand the intensity of radical treatment. The dose given is balanced between the need to control symptoms and reduce morbidity. Tissue tolerance to Radiotherapy Mucositis: develops about 3 weeks after the start of radiotherapy, the intensity of this condition depends on the total dose of radiotherapy delivered. Patient usually unable to eat or swallow, Mucositis heals within about 2-4 weeks of completing radiotherapy. The principles of pathophysiology of mucositis, production of free-radicals caused by chemo or radiotherapy which damage cell DNA. Dry mouth (xerostomia): the effect of radiotherapy on salivary function may be appearnt within the 1st week of treatment, as treatment continues saliva become stickier leading to difficulties in swallowing and it is a common cause of nausea because of the collection of the sticky secretions in the oropharynx and hypopharynx. In practice it is difficult to shield the parotid and submandibular gland with conventional radiotherapy. Skin: Erythema normally develops in the 3rd week of the treatment. Healing take place 7-10 days post treatment. Osteoradionecrosis: (ORN) is a debilitating late complication of radiation therapy. ORN is a chronic side effect that develops slowly and tends not to heal spontaneously. Biologically the process is characterized by inadequate repair and repopulation and by a reduction in the vascular potential of the tissues. This hypovascularity with attendant hypoxia reduce cellular activity. Treatment of osteoradionecrosis relies on a combination of conservative measures (antibiotics, Oral cancer Dr. Hani Al Sheikh Radhi 2016 debridement, and irrigation) and surgical resection (sequestrectomy, marginal mandibulectomy, or segmental mandibulectomy with or without reconstruction) formation and wound healing. Using hyperbaric oxygen (HBO) chamber may be helpful. Theory that osteoradionecrosis is a result of hypoxia, hypocellularity, and hypovascularity, HBO seems like an attractive option. It increases oxygen supply in hypoxic tissue, stimulating fibroblast proliferation and angiogenesis.