Pathology of the facial sinus cancer
Many authors and literature in the world are based on anatomy, embryology is divided into 3 categories: superstructure carcinoma, mesenchymal cancer, and structural cancer.
Cancer of the facial sinuses refers to lesions in the nose, sinuses, and facial jaw. The facial sinuses include anterior and posterior sieve, maxillary sinus, parietal sinus, and frontal sinus. The most common is cancer of the sinus and sinuses. When one of the two sinuses has cancer, it is more likely that cancer will invade the nearby sinuses.
In fact, the term "cancer of the facial sinuses" is also not anatomically accurate because malignant tumours in this area usually appear from the upper jaw bone, or from the vicinity of the maxilla, for example. For example, primary cancer can be from the anterior sieve, or the posterior sinus or from the palate bone. Cancer spread into the jaw sinus causes sinus cancer symptoms.
Factors related to pathogenesis
With local chronic inflammatory lesions such as degenerative lesions, degenerative sinusitis into polyps with clinical sinus cancer.
Due to occupational diseases: chemical exposure such as workers in contact with nickel, arsenic, chromium, amiant ...
The most common type is slice carcinoma (accounting for over 80%), often damage originating from the mucosa covering the facial sinuses and nasal cavities. The epithelial type of the upper mucous membranes is brachial cells, the cancer comes from there being slice and due to the inflamed sinuses leading to slice cell legacy and pre-cancerous properties. letters. This type of carcinoma is generally a form of epidermal carcinoma and rarely has keratinocytes.
And the cancer of the link (sarcoma) is less common and has more types. These are: cartilage sarcoma, bone sarcoma, fibrosarcoma (fibrosarcoma), marrow sarcoma, tongue sarcoma ...
Because the facial sinuses are closely related anatomically, the clinical symptoms, although very diverse, can be inducted into the following 5 syndromes:
Nasal Syndrome: most common, manifestations of stuffy nose on one side, runny nose with mucus or blood, nose bleeds.
Eye syndrome: pain in the fossa, eyeball, tearing eyes, tearing of the tear.
Deformation syndrome: bulging eyes, bulging cheeks, dilated nasal roots, missing nasal-cheeks, jaw stiffness ... depending on the location and spread of the tumour.
Neurological syndrome: headache, pain in the frontal area, facial numbness, loss of smell, loss of vision, blindness ...
Cervical lymphadenopathy: usually appears in a late stage.
Classification of facial sinus cancer
Many authors and literature in the world are based on anatomy, embryology divided into 3 categories: superstructure cancer, structural mesenchymal cancer, and structural cancer.
Structural superstructure cancer
Mainly refers to cancer of the anterior and posterior sinuses, which comes from the sieve cells. In fact, this type of tumour is usually in the boundary between the sinus and the jaw, so it is also called "border cancer". This type of cancer includes can arise from the upper and posterior corners of the jaw sinuses.
Sinus cancer screening first
Commonly, Malpighi carcinoma and cylindrical carcinoma.
Malpighi carcinoma: is carcinoma of no differentiation, cancer cells are cylindrical or long, or have mitosis and multiplication. A few rare cases are carcinoma of less differentiated and may be scattered, possibly with keratinocytes.
Cylindrical carcinoma: usually detected on a sinus mucosa that has not yet developed to Malpighi dysplasia, in the previous organizational study, it was also classified as adenocarcinoma as a type of tumour more or less normal, atypique and mucous carcinoma are mucus-producing cancers.
Sinus cancer screening later
Derived from the posterior group of sieve cells, that is, the posterior group and the medial hemisphere (the posterior sieve group, the sieve-cell group, and the butterfly-sieve cell group) can spread to the meninges. hard. In contrast, pre-screening sinus cancer because there is a bone gap between the anterior and the posterior screen, it rarely spreads to the hard meninges. Post-screening sinus cancer usually spread very quickly outward, because the tissue is very thin, easily destroyed, the tumour spreads into the eye socket, so when the tenon is infected, many authors believe that the eyeball must be removed. Spread to the back is the butterfly sinus, so it is more often superinfected. If the tumour has spread to the front and floor of the butterfly sinus then these 2 parts must be removed.
Clinical symptoms: because the tumour is in the cavity, when it has not spread out, the symptoms are very discreet, easily confused with chronic clinical sinusitis. In fact, the majority of patients come to the examination in the late stage, so the common symptoms are nasal congestion, nosebleeds, eye and nose pain, swelling of the rhizome, nose-eyes, causing eye syndrome. bridge.
Nasal congestion: usually one side and progresses from mild to severe, complete stuffy and accompanied by nosebleeds, mucus.
Nasal bleeding: is an important symptom that can bleed spontaneously or by impact ... nosebleeds are increasing in number and amount of bleeding (when examining, it was not bleeding at venous point due to high blood pressure.).
Pain: usually occurs later and is less common at this stage, the patient has a feeling of severe feeling in the rhizome or forehead, in some cases, there is a severe pain in the forehead.
Swelling of the nose-eyes area: in reality the most common is the sign of "deformation of the face and eyes" because the tumour spreads beyond the limit of the sinuses, causing the nasal roots to swell, swelling of the cheeks and especially the variable a parietal eye-eyeball (eyeball protruding anterior and outward), sometimes with swelling of the upper eyelid. Also, in some patients there is a phenomenon of decreased vision, double vision. Some individuals are superinfected in the tears area.
Nasal congestion: this is also a common sign that 60% of patients have had this sign when they come to the examination, because the tumour gradually begins to block on one side, then the tumour pushes the septum to the opposite side and causes obstruction of the two sides. causes the patient to breathe through the mouth.
Nasal bleeding: at this stage, patients often have nosebleeds, accounting for 30%), the amount of blood is more or less depending on the patient, some people have a little blood in the nose, some people have dripping fresh bleeding. but most of it is bloody mucus. In particular, someone with massive bleeding requires emergency care. Therefore, patients with a history of nosebleeds should be cautious to have a biopsy (preferably for patients staying in bed).
Olfactory disorder: This symptom is uncommon, if any, due to a tumour in the upper part of the sinus or olfactory nerve tumour. The sense of smell can be reduced, but it can also be completely lost, caused by damage to the olfactory nerve cells or by the tumour blocking air circulation.
Malformations: because the tumour has spread beyond the sinus area and breaks down the anterior and outer wall of the sinus causing the inner corner of the eye to bulge or the eyeball to bulge, this symptom is important in diagnosis.
Eye symptoms: in addition to the bulging eyeball, there are also some other common eye symptoms such as: tearing eyes, tear gland inflammation, eyelid ooedema sometimes conjunctivitis, which often makes patients come to visit. ophthalmology first.
Nasoscopy: usually nasal passages contain a lot of mucus secretions and pus that smell bad because of superinfection. After cleaning the nasal discharge can be seen in the high, upper part of the nasal cavity or middle nasal passages have an organized, bleeding easily, often the nasal folds are swollen, erect so that requires anaesthesia and medication Pre-vasoconstriction to check more clearly. In some cases, the shape looks like a smooth, pink polyp that is firmly attached to the nasal fold or middle nasal passages like a chronic inflammatory organ, while the cancer is often hidden in the deep, so later When the polyps are cut, the new tissue will reveal clearly.
Post-nasal exam: very important but requires good anaesthesia to check. In many cases, posterior noscopy shows no lesions while the anterior nose is full of tumour lesions, when the tumour has spread to the posterior nasal opening, there is usually a granular organization that can cover both the posterior nose and spread into the arch. If the tumour is superinfected, there may be an ulcer or a pseudo membrane covering.
Tumours spread to the frontal sinus: Pre-clinical sinus cancer often causes frontal sinus infection so it is sometimes difficult to determine if there is an infiltrate, because the clinical symptoms are similar to a common frontal sinus infection in the corner of the eye and pain at a certain time, usually in the morning, can only be based on X-ray images to make a partial judgment. Turns into polyps, cancer organizations often mix in these mucosae, so biopsy must cut many specimens.
Tumours spread to the butterfly sinuses: this is less common in the frontal sinus. The clinical symptoms are very difficult to determine, the diagnosis based on X-rays, especially the CT Scan can clearly show the damaged anterior butterfly sinus wall.
Tumours spread to the jaw sinus: is the most common case in Vietnam. At this advanced stage, it is difficult to distinguish which is the primary cancer of the sinus, so it is often called sieve cancer. Anatomically, it is rare that cancer from the anterior sieve spreads to the maxillary sinus because the anterior sieve is directly related to the lower inner sinus. In contrast, the tumours in the posterior sieve usually spread downward and outward, so they often spread to the jaw sinuses. The clinical symptoms showing the infiltration down the jaw sinuses are a sense of numbness of the skin in the nasal-cheek groove corresponding to the dominant nerve under the eye socket, this numbness spreading to the upper lip sometimes. on the inside of the upper lip. Some patients have a feeling of heaviness in the jaw sinus area and are often accompanied by superinfection of a sinus infection, with purulent discharge with bloody mucus. X-rays, especially CT Scan scans, will help us see these infiltrates. In fact, in cases of cancer of the jaw screen, over 30% have signs of infiltration of the eye, eyeball area.
Tumour spread into the fossa of the jaw: this case appears late and has the following manifestations: pain in the mandibular nerve and the region due to the maxillary nerve. The ooedema of the eyelids, temporal fossa, and jaw stiffness is the latest and progresses slowly, after which the calf muscles of the jaw are also infected.
Tumours spread to the hard meninges and brain: the last and most severe stage of clinical sinus cancer, the patient often has a severe migraine on the side of the disease, diagnosed by X-ray especially when taking CT Scan, we can clearly see that the sieve is corroded and destroyed. At this stage, treatment is mainly symptomatic.
Intermediate structural cancer
Is cancers of the jaw sinus stems from the mucosa or bone wall of the jaw sinuses. Statistics of many authors have many different points, some comments that sinus cancer is less common than the clinical sinus. According to the comments of some authors: Sinus cancer accounts for a higher rate than jaw sinus cancer.
Early stage: the clinical symptoms of sinus cancer are very inconspicuous and nonspecific and very similar to the symptoms of a common chronic sinusitis, such as unilateral congestion, gradually increasing and often accompanied by superinfection, so or with runny nose, sometimes bloody. Sometimes, patients complain of oil pain, but it is not so severe, and using painkillers is better. Pre-nasal examination at this stage usually does not detect any lesions except in some cases of patients in the middle nasal passages with purulent or bloody mucus, due to superinfection, the mucosa of the nasal folds or the nasal passages is often red oedema, congestion, particularly with cavity organization, easy to bleed to the touch.
Summary: It is very easy to confuse it with chronic jaw sinus cancer in the early stages (so in fact some patients have been diagnosed and treated as a chronic sinus infection). Some when new surgery is suspected to have cancer due to abnormal lesions of the mucosa or sinus wall, there are some bleeding phenomena at the time of surgery and most typically, not long after surgery, the disease will return rapid and malignant disease (increasing headache, swelling half of the face of the surgery, even appearing neurological symptoms and deformation of the nose, cheeks ...).
Visible stage: the patient usually arrives at this stage to the hospital; the symptoms increase gradually both in intensity and time. Headache or soreness in the fossa and cheeks. Feeling numb under the orbit or half of the face of the disease. In addition, due to superinfection of the sinus area, in addition to congestion, nose often blows with blood and stench.
Front nasal examination: seeing that the nasal-sinus septum was pushed inward, the middle nook was organized, easy to bleed depending on the big and small tumour, but the nasal cavity was partially or completely occupied, the septum could be cornered. opposite side causing stuffy nose on both sides and a closed nose voice.
Post nasal scan: there may be some cases that have spread to the back of the nose or into the arch.
Implementing the quadrants
It is often difficult in the early stages. Most patients often arrive late, so it is possible to rely on clinical symptoms, physical examination, biopsy results and X-rays (Blondeau, Hirtz, CT Scan) to make an accurate diagnosis. The problem is assessing lesions in order to have an effective treatment regimen.
Chronic sinusitis: pain caused by cancer is often more intense and pain relievers will gradually lose their effects, usually pain in the upper jaw area, eye socket area, nasal secretions are often purulent fluid mixed with blood. on X-ray, the jaw sinus image is evenly blurred, widened, the edge is irregular and the bone wall of the sinus is destroyed.
Cyst around the teeth: this type progresses slowly, the clinical symptoms are not clear, the patient's condition is normal, there is no sign of infiltration on the spot, the X-ray film can clearly see the edge of the cyst.
Benign tumours of the jaw sinuses: such as mucous tumours, bone tumours, cartilage tumours, fibroids, these tumours usually progress very slowly, are painless, no superinfection, less exudate, x-rays often have blurred images evenly, clearly.
Tricyclic neuralgia or toothache usually hurts in series, pain in each episode and without deformation phenomenon.
Fungal sinusitis: the disease progresses slowly, normal general condition, rarely has lymph nodes but wide infiltrates, so often there are many fistulas.
Gum cancer: it is easy to confuse with the outward form of papilloma tumour, so it is necessary to examine carefully.
Progression of the disease
Clinical signs also vary depending on the spread of the tumour.
If the tumour spreads to the front of the jaw sinuses, push the fangs and cheeks.
If the tumour spreads to the top of the jaw sinus, breaking the floor of the orbit, the eyeballs are pushed upward and forward, causing swelling of the lower eyelid, which can spread to the cheekbones and sieve.
If it spreads to the sinus sieve, the cancer-like symptoms from the sinus sieve spread to the jaw sinus and it is difficult to determine the starting point of the cancer.
If the tumour spreads to the bottom of the maxillary sinus, the female palate is broken, then the palate mucosa is infiltrated and then spread to the root, causing the teeth to shake and fall out.
If the patient is not treated, the disease will develop very quickly, widespread local lesions accompanied by superinfection, the patient gradually deteriorates due to pain, inability to eat, and eventually leads to death or bleeding. mass in the large blood vessels of the face (necrosis associated with superinfection and widespread cancer) either due to physical depletion accompanied by a superinfection in the sieve or by distant metastasis.
Also known as dental cancer, oral cancer to clarify the location of the cancer and its relationship with the dental specialist. Cancer lesions usually originate from the alveolar boundary of the maxilla. This type of cancer has the advantage of being easily detectable at an early stage due to its obvious symptoms, except in some isolated cases (when the disease has spread) it is difficult to identify primary cancer.
Persistent toothache, sometimes severe pain, the teeth can be loose, so when the patient came to the examination, the tooth was extracted from a previous gland, but the pain did not decrease but increased. If you examine carefully, you will find that the root pockets of the extracted teeth do not heal, but also sprout buds or organize seeds, easy to bleed to the touch. These lesions increasingly spread and infiltrate to the surrounding gums, causing the lip groove to bulge and the teeth to be loose. The mucous membrane of the gum area is also infiltrated, it becomes dark red, has many blood vessels converging, the mucosa of the palate is also swollen down, making us mistakenly believe that cancer is originating from the frog's jaw. Later, the cheeks were also swollen because the cancer lesion had infiltrated the area around the canines. In some cases, cancer lesions arise from the early infiltration of the incisors and palate, then spread to the lateral jaw. In some cases, this cancerous lesion is superinfected, causing necrosis, rotting pus like an inflammatory pulp of the pulp. If the cancer comes from wisdom teeth, it is easy to penetrate into the pothole and cause the jaw to close, this case is very similar to a sign of an erupted wisdom tooth or an epithelial cancer of the gums. When the cancer has spread into the fossa and caused the jaw to close the patient is very painful,
In general, it is not very difficult, based on clinical symptoms, examination to detect, biopsy also to correctly remove cancer lesions. In addition, on X-ray film (Hirtz potential) found a lesion of the jawline which is difficult to assess clinically.
Full stage (spread) of cancer of the facial sinuses: diffuse cancer of the upper jaw is called as an author. This is the final stage of the cancer of the facial sinuses that has spread to neighbouring areas no longer able to determine where the cancer started. In this stage, the patient's face becomes monstrous due to cancer damage that destroys the bone structure and spreads to the software. The general condition of the patient also deteriorates rapidly, accompanied by superinfection, so there is no possibility of treatment anymore. Mainly symptomatic treatment, anti-superinfection and analgesia, because according to autopsy results, many authors have recorded that 65% had distant metastases.
Some other forms of nasal and sinus cancer
Cylindromes (cylindromes) are less common than carcinoma but not uncommon. In 1859 Biltroth was the first to describe this type of tumour. The noun cylindrical tumour also derives from the shape when read on the specimen of the lesion (cylinder). Thesis of Yveslé-Maltre (France) is quite complete about this disease. This word is rarely used in English literature. In general, the previous literature is also known as basal cell carcinoma (pressedithélioma à cellules basales).
Pillar tumours are characterized by a cluster of tumours, ovoid (oval), luminous (hyatin) or mucous. Due to being uniform ovoid shapes, they are sometimes lattice. The stroma is very variable, usually the fibrous organization that forms the septum dividing the clusters of cells into the lobe. Pillar tumours usually originate from the glandular organization, progress gradually and very slowly, especially there is no lymph node metastasis but has metastasis to the lungs. The location of the cylindrical tumour can be from the sieve is commonly seen as the anterior lateral mass, rarely seen in the posterior part, in fact commonly seen in the upper part of the septum.
The slow growth of the tumour pushes the nearby organs, does not cause infiltration, but the adjacent bone walls may become holes or disappear. After resection of the lesion, lesions can be relapsed, although the length of time may vary. Distal metastases are common in the lungs, but must be after many years, sometimes 10-15 years.
Without treatment: the disease progresses in waves, with stable or regressive intervals lasting many months. Especially when the disease has had lung metastases, progressing slowly, such as primary damage to the nose and sinuses, so many authors commented that, in patients with tumours already had lung metastases, still Surgical treatment can be performed without affecting tumour growth and lung metastasis.
Treatment of carcinoma of the facial sinuses
Surgery combined with radiation is now the main treatment for this type of cancer. In recent years, there have been many encouraging reports of additional combination with chemicals before and after surgery, radiation.
The choice of surgical method depends on where the cancer has spread. With the architectural superstructure, when the tumour is not too widespread, it is possible to cut a part of the upper jaw bone, part of the lower wall and the inner wall of the eye socket along with the main bone of the sick side nose. With mediastinal tumours: the majority of patients arrive at a late stage, so many authors actively remove the entire upper jaw bone. As for architectural infrastructure tumours based on specific lesions, conservative surgery (cutting a part of the upper jaw bone) is performed.
As an important combination, it can be used two ways: usually the Co60 transdermal radiation, the daily dose and the total dose as well as other cancers of the head, face and neck area, usually 2Gy / day, from 10 per week -12Gy (for 4-5 weeks). Some authors advocate applying radiation sources right into the surgical pits, often using Co60 or radium sources, recently many people use indium192 because their experience shows that radium often causes sinus necrosis and many serious complications.
Chemicals can be used intravenously or arterial. The common chemicals used are 5Fu, Bléomycin, Cisplatin. The treatment of chemicals in the combination treatment of nasal and sinus cancer is very concerned by the Japanese school.
20 years ago, when it came to nasal and sinus cancer, especially when the tumour had spread over one anatomic area (more than one sinus), the treatment outcome was generally bad. complications and sequelae for the patient should have a bad prognosis. Recently, many authors have made better comments due to the combination of treatment between surgery, radiation and chemicals.
If only radiation treatment
The results were very poor, according to Lederman of 55 patients with clinical sinus carcinoma, only 5% live more than 5 years. But according to Errington (1985), treated 43 patients with widespread nasal and sinus cancer (85% of T4) with low energy neutrons (7.5 MeV) for 17 patients with epidermal cancer, 11 Pillar tumour, 8 adenocarcinoma, 5 transitional carcinoma, 1 undifferentiated carcinoma and 1 malignant melanoma, the result is 47% and 72% longer life expectancy, and after 5 years are 30% and 55%. The author commented that the reason to achieve the above results is due to the organizational properties of the tumour, due to the effect of neutrons compared to photons with oxygen-deficient cells.
If simple surgical treatment
Then should only apply to small tumours, have not spread to the sinus area or nearby organizations. The best results are for carcinoma of the structural infrastructure, 30-50% can live more than 5 years.
If the combination of surgical treatment with radiation, the results are clearly the highest compared to the two methods above. The problem is pre-radiation or pre-surgery. Many reports show that the results of the pre-surgery or pre-surgery are not much different. The argument of the pre-radiation school is to rejuvenate tumours, especially to destroy very small cancers scattered around the main lesion that the naked eye cannot see and can spread far during surgery. technique. The post-operative radiation school emphasizes the anti-ray properties of tumours that have spread to the bone, and also commented that before surgery, the incision will heal better. Combining postoperative radiation is a common treatment method.
Combining surgery with radiation for nasal sinus carcinoma in general can achieve a survival result of over 3 years about 55% and after 5 years about 48% (Gustave Roussy Institute in France 1990). Recently, many Japanese authors (Yamashta, Sato, Sakai, Shibuya et al.) Have reported many reports stating the results of using chemicals (using a substance or substances) in combination with surgery and radiation. has improved the effectiveness of treatment as well as avoids an overly extensive surgery (replacing a full maxillectomy with a partial jaw removal surgery) these results are still in the real stage. Experiences and opinions differ; however, the use of chemicals is widely applied in many countries in this field.
Frontal sinus cancer
This type of cancer is rare, often secondary to the infiltrate of the sinus, mainly adults and both sexes with the same disease, about more than 80% of the organization of the type of carcinoma, and sarcoma. very rare.
In the early stages, symptoms resemble a chronic frontal sinus infection or purulent frontal sinusitis. The majority of patients at the examination are usually in the late stage, so the more obvious symptoms such as severe headache, or the tumour has broken the anterior sinus wall, causing the root area and the skin at the corner of the eyebrow to be pushed. bulging.
Implementing the quadrants
Based on the clinical findings, the disease progresses quickly, easily breaks the bone walls to penetrate the surrounding areas, on X-rays clearly see the broken bone walls.
In the early stage, it should be differentiated from a chronic sinusitis, with a frontal sinus tumour. These diseases have a long history and progression, the symptoms are not prominent, on X-rays with blurred images, there is no bone destruction phenomenon.
In the flaring stage, it should be distinguished from frontal sinus tumours, with a long history of years, sometimes 8-10 years, the whole body is not affected, physical examination and X-rays have specific signs. features of mucus (soft tumour, pressed feels like a ping-pong ball, poked with a large needle to suck mucus, on X-ray bone wall is corroded, not destroyed ... ).
Treatment and prognosis
Mainly coordinated surgery with radiation, but most patients come to the examination in the late stage so the treatment capacity is very limited and patients often die from meningitis or brain infiltration.
Butterfly sinus cancer
Also, very rare, usually carcinoma, very few sarcomas.
In the early stages the symptoms are very discreet and poor, to a pronounced stage the symptom is very similar to a purulent butterfly sinus infection, but progresses rapidly and worsens, the patient has a constant headache and then the tumour widespread, causing severe symptoms such as: neuritis leading to blindness, meningitis, cavernous sinus thrombophlebitis and other neurological syndromes. In addition, the general body deteriorates and is often accompanied by superinfection.
Nasoscopy after or through Eutaschi tube bronchoscope (Salpingoscopie) can clearly show cavities in the butterfly sinus cavity.
On the film Hirtz and tilted skull showed a shadow of the tumour and bone destruction phenomenon.
In fact, the patient came to the examination in a late stage, so the diagnosis is not very complicated, especially the terminal disease, the cancer has spread to the neighbouring areas.
Up to now, the treatment method for butterfly sinus cancer (primary or secondary) has faced many difficulties and the results are very limited because of the anatomical position of the tumour as well as the late stage of the patient's visit. Most die from brain complications.
Types of sarcoma of the facial sinus area
There are many different types of sarcomas in the facial sinuses, the diagnosis is entirely based on the results of the organization. in sinus cancers from 7-15%. Commonly, fibrosarcoma, cartilage sarcoma (chondrosarcomas), bone sarcoma, rhabdomyosarcomas, angiosarcoma ...
Depending on the location of the tumour's infiltration, the clinical symptoms are different (such as clinical sinus cancer, sinus cancer, sinus cancer, frontal sinus, infrastructure ...). Especially, sarcoma differs from carcinoma type which progresses very quickly, common in children and the elderly (before 15 years old and after 65 years old) but can also be found at any age.
Mainly based on clinical symptoms, especially rapid disease progression, based on biopsy results and X-ray film.
If not diagnosed and treated promptly, the disease develops very quickly locally and soon has distant metastases (often the lungs and bones).
Sarcoma is generally sensitive to radiation and chemicals, so treatment is primarily a combination of radiation with chemicals. The method of coordination depends on the stage of the disease as well as the forte of the clinical physician, possibly with prior rays or chemotherapy first, or alternating chemical-radiation-chemical combinations.
In general, the disease will be in remission very quickly, with very encouraging immediate results, but the rate of local recurrence or metastasis is also common, especially within the first 2 years after treatment so patients need to be monitored. regularly to promptly handle if a relapse occurs. Some advocate for periodic chemotherapy injected or taken with fortified doses. These are also controversial opinions.