Ethanol Injection For Treatment Of Thyroid Cancer Biology Essay

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Thyroid is a small butterfly shaped gland at the base of the throat and the function of thyroid gland is to make, store and release thyroid hormones that helps in controlling heart rate, blood pressure, body temperature and weight. Thyroid hormones regulate the body's metabolism and influence the heart rate, cholesterol level, body weight, energy level, muscle strength, skin condition, menstrual regularity, memory function and many other conditions. Thyroid cancer is a disease in which cancer cells form in the tissues of the thyroid gland. Each year in the United States, more than 25,000 women and 8,000 men learn they have thyroid cancer. Estimated new cases from thyroid cancer in the United States in 2010 are 44,670 and estimated deaths are 1,690. 1-4

Types: Mainly there are four types of thyroid cancers. Papillary Thyroid Cancer and Follicular Thyroid Cancer are two types of thyroid cancers which begin in the follicular cells of the thyroid. Third type is the Medullary Thyroid Cancer which begins in the C cells of the thyroid and makes abnormally high levels of Calcitonin. Fourth one is the Anaplastic thyroid cancer which also begins in the follicular cells but is difficult to control. Except for the Anaplastic thyroid cancer which grows and spreads very quickly, all other types of thyroid cancers grow slowly. Papillary and Follicular thyroid cancers can be cured if diagnosed early, Medullary can be controlled if diagnosed before it spreads to other parts of the body. Papillary thyroid cancer makes up about 80 % of all the thyroid cancer cases in the US, Follicular 15 %, Medullary 3% and Anaplastic 2%. 1-4

Signs and Symptoms: It is usually seen as a nodule in the thyroid region of the neck but less than 5% of these nodules are malignant. But the potential for malignancy is high for those who develop thyroid nodules under the age of 20 years. A lump in the front of neck, swollen lymph nodes in the neck, pain in the anterior region of the neck, change in the voice and difficulty in swallowing or breathing are the symptoms that are usually present. Sometimes, tumors that are large or a metastatic well-differentiated tumor may be associated with Hyper or Hypothyroidism and these symptoms may also be present along with those of thyroid cancer. Factors like age, gender and exposure to radiation increases the risk of developing thyroid cancer. Rarely, a change in the gene passed from parent to child can also be a cause of thyroid cancer. 1-4

Diagnosis: Thyroid cancer can be diagnosed with the help of personal and family medical history, physical examination, blood tests and thyroid scan. An ultrasound is performed to confirm the presence of a nodule and also to assess the status of the whole gland. Thyroid stimulating hormone and anti-thyroid antibodies are measured to rule out any functional thyroid disease like Hashimoto's thyroiditis. Fine needle aspiration or surgical biopsy can also be done to confirm the diagnosis. Ultrasound, Chest X-ray, Whole body scan, MRI and CT scan are helpful in staging the cancer. 1-4

Treatment: Thyroid cancer can be treated by surgical resection of the thyroid gland or with thyroid hormone treatment or radioactive iodine therapy. External radiation therapy or Chemotherapy are also used in treating thyroid cancers. Common surgeries include total thyroidectomy and lobectomy. The treatment choice depends on the type of thyroid cancer, the size of the nodule, metastasis and also the age of the patient. There is a possibility of recurrence even when there are no signs and so there is a need for regular checkups. 1-4

Percutaneous Ethanol Injection (PEI)

Percutaneous ethanol injections contain alcohol and with a very thin needle it is injected through the skin percutaneously into the tumor with the help of ultrasound or CT guidance. The cancer cells are killed by the injected alcohol that dehydrates the cells by withdrawing water from these cells which in turn causes an alteration in the cellular structure. The tumor cells are destroyed in this process but not at a time and the complete destruction of the cancer cells occur only when this technique is repeatedly done almost 5-6 times. This technique is more useful for patients who have well defined cancer; diameter less than 3 cm and is surrounded by scar tissue. While using this technique, the location of the tumor should be identified exactly to avoid any injury and there is always a possibility of alcohol leakage leading to symptoms like pain and fever. Usually, PEI is done as an alternative to surgery for preventing the growth of the cancer particularly the recurrent ones. 1-4

Kunihiro Nakada, a clinical assistant professor in the department of radiology at Hokkaido University, presented a study at the annual meeting of the Society of Nuclear Medicine, in Washington, D.C. in 2007 and said in a prepared statement that PEI appears effective in terms of palliation (control) of symptoms (such as pain) and tumor size reduction and does not induce significant systemic side effects. In addition, PEI is a feasible treatment for radioiodine-ineffective tumors and has a potential for improving general performance or quality of life for selected patients.4

Medical guidelines on PEI for the diagnosis and management of thyroid nodules from the American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi are listed in Appendix II.

Methodology:

A broad literature search was done to assess availability of studies or trials relevant to the topic. A final literature search was done in PUBMED, Google Scholar, Google search engine(s) using various combinations of keywords like Ethanol Injection and Thyroid Cancer etc. using AND, OR and NOT (Boolean operators). All relevant articles were selected, data extracted and analyzed to write a report.

Glossary:

PEI - Percutaneous Ethanol Injection

US - Ultrasonography

FNA - Fine Needle Aspiration

AFTN - Autonomously Functioning Thyroid Nodules

PTC - Papillary Thyroid Carcinoma

NR-PTC - Neck Recurrence of PTC

PEIT - Percutaneous Ethanol Injection Therapy

RFA - Radio Frequency Ablation

EtOH - Percutaneous Ethanol

WTC - Well Differentiated Thyroid Carcinoma

CT - Computed Tomography

TTNs - Toxic Thyroid Nodules

RAI - RadioIodine

NV - Nodular Volume

SYS - Symptom Score

Evidence Review:

Five studies were selected and included in this review after literature search, abstract review and full text article review.

Kim BM et al. (April 2008; Level III) conducted a retrospective analysis to evaluate the efficacy of ultrasonography-guided percutaneous ethanol injection (PEI) for neck recurrence of papillary thyroid carcinoma (NR-PTC). Twenty-seven patients were treated by PEI (Percutaneous Ethanol Injection) for NR-PTCs (Neck Recurrence of Papillary Thyroid Carcinomas) between September 2003 and December 2005, and were followed up to January 2007 (mean, 28.2±6.3 months; range, 14-38). The patients consisted of 5 men and 22 women, and the patient's average age was 53.2 years (range, 19-80 years). The inclusion criteria for PEI were as follows: (1) the presence of three or fewer NR-PTCs and no recurrence beyond the neck at the PEI point in time, (2) the NR-PTCs were not close to vessels to avoid the potential risk of ethanol intravasation-this is a precaution just based on the authors' opinion-and (3) the patients with NR-PTCs were poor surgical candidates (the patients with high risk for general anesthesia due to a medical condition or for surgery due to repeated neck dissection) and/or preferred not to have further surgery. The main Outcomes were the number of sessions per NR-PTC (times), total volume of ethanol used per NR-PTC (mL) and the volume of ethanol used per session per NR-PTC (ml/session). Other Outcomes were Pretreatment maximum diameter of the NR-PTC (mm), Maximum diameter of the lesion on the last follow-up ultrasonography (mm), Pre-treatment volume of the lesion (mm3), Volume of the lesion on the last follow-up ultrasonography (mm3), Volume decrease and Follow-up period of each lesion (months). The NR-PTCs with decreased volume and no tumor vascularity on power-Doppler study were regarded as treatment-effective. The NR-PTCs with stable or enlarged volume or with tumor vascularity were considered as treatment-failed, in which case PEI was repeated. The number of sessions and the total volume of ethanol per NR-PTC, and the volume of ethanol per session per NR-PTC were evaluated. All NR-PTCs significantly decreased in volume (range, 30-100%; mean, 93.6%). The mean number of sessions, the total volume of ethanol per NR-PTC, and the mean volume of ethanol per session per NRPTC were 2.1 sessions (range 1-6), 2.4 ml (range 0.3-10.1), and 1.1 ml/ session (range 0.3-3.0), respectively. Limitations of this study include the small number of patients, the short follow-up period, and the retrospective nature of the study. The authors concluded that PEI was effective for controlling the NR-PTCs. The results of this study suggest that PEI may be an alternative treatment option for control of NR-PTCs in selected patients who are poor surgical candidates.5

Lim CY et al. (April 2007; Level II-2) conducted a prospective cohort study to evaluate the local therapeutic effect of PEIT in recurrent thyroid cancers. The patient cohort consisted of 16 patients, six at high-risk for general anesthesia and reoperation due to cardiac or pulmonary diseases and 10 who refused to undergo reoperation. Of the 16 patients, three were men and 13 were women; their mean age was 66 years (range, 31-74 years). Sixteen consecutive patients who underwent PEIT between October 2002 and September 2005 due to local recurrence of differentiated papillary thyroid carcinoma at the site of surgery or in cervical lymph nodes during follow-up were included in this prospective study. The main outcomes were the amount of injected ethanol, the frequency of injection and the side effects. The mean lesion size was reduced from 9.9mm (range, 5.5-29.0mm) prior to the first injection to 5.3mm (range, 0-17mm) after the last injection. Thyroid bed lesions were reduced from 11.8mm (range, 5-21mm) to 5.5mm (range, 0-14 mm), and cervical lymph node lesions were reduced from 8mm (range, 6-29mm) to 5mm (range, 0-20 mm). All the lesions were decreased in size. Follow-up ultrasonography showed that four lesions disappeared completely, after an average of 1.2 injections. The authors concluded that the study findings showed that PEIT is a safe, nonsurgical treatment modality that is effective in reducing locally recurrent thyroid carcinoma and in reducing disease progression in appropriately selected patients. Large, prospective, long-term follow-up studies, however, are required to fully evaluate the effect of PEIT on survival rate and recurrence of papillary thyroid carcinoma.6

Monchik JM et al. (August 2006; Level III) conducted a retrospective analysis to assess the long term efficacy of radiofrequency ablation (RFA) and percutaneous ethanol (EtOH) injection treatment of local recurrence or focal distant metastases of well-differentiated thyroid cancer (WTC). Sixteen adult patients (ages, 28-84 years; mean, 53 years), 12 women and 4 men who underwent percutaneous RFA treatment of biopsy-proven recurrent well-differentiated thyroid cancer in the neck. All patients treated with RFA or EtOH ablation who had a normal platelet count and normal coagulation parameters were included in the study. No patient was taking antiplatelet medications or anticoagulants for at least 1 week before the procedure. Clinical follow-up consisted of routine ultrasound, 131I whole body scan, and/or serum thyroglobulin levels for recurrence at the treatment site. No recurrent disease was detected at the treatment site in 14 of the 16 patients treated with RFA and in all 6 patients treated with EtOH injection at a mean follow-up of 40.7 and 18.7 months, respectively. Two of the 3 patients treated for bone metastases are free of disease at the treatment site at 44 and 53 months of follow-up, respectively. The patient who underwent RFA for a solitary lung metastasis is free of disease at the treatment site at 10 months of follow-up. No complications were experienced in the group treated by EtOH injection, while 1 minor skin burn and 1 permanent vocal cord paralysis occurred in the RFA treatment group. The authors concluded that RFA and EtOH ablation show promise as alternatives to surgical treatment of recurrent WTC in patients with difficult reoperations. Further long-term follow-up studies are necessary to determine the precise role these therapies should play in the treatment of recurrent WTC.7

Zingrillo M et al. (February 2003; Level I) conducted randomized comparative study to evaluate the efficacy of 2 nonsurgical modalities for toxic thyroid nodules (TTNs). From January 1997 to December 1999, 22 patients with TTNs larger than 4 cm who were referred to their hospital for previously untreated TTNs. Patients were randomly assigned to 2 different treatments: to 11 (subgroup A), RAI was administered at a dose of 12,580 kBq/mL of nodular volume (NV) and was corrected for 100% 24-h 131I uptake (RAIU); to 11 (subgroup B), 2-4 PEI sessions (ethanol injected 30% NV) preceded 2 mo of 24-h RAIU and RAI dosing. Inclusion criteria were clinical and biochemical hyperthyroidism; a single palpable, hot nodule at 99mTc scintigraphy; and high surgical risk or refusal to have surgery. There were clinical, hormonal, scintigraphic and ultrasonographic Outcomes. At 6 and 12 months after RAI administration, a clinical evaluation, calculated SYS, and determined serum FT3, FT4, and TSH levels and NV using ultrasonography were performed in all the patients. A new scintigraphic picture was obtained for all patients 6 months after treatment. Both treatments were well tolerated. Subgroup B showed a significant reduction of NV 2 mo after PEI: 33.6 18.5 versus 60.8 29.5 mL. Their 24-h RAIU was similar to that of subgroup A: 53.9 13.9 versus 61.8% 11.0%. Consequently, the administered RAI dose was significantly lower for subgroup B (730 245 MBq) than for subgroup A (1,048 392 MBq). Twelve months after RAI, subgroup B had a higher NV reduction and a lower SYS than did subgroup A. In subgroup A, 1 patient was subclinically hyperthyroid, 2 showed a slight increase of thyroid-stimulating hormone, and 1 was clinically hypothyroid. In subgroup B, 1 patient had a slight increase of thyroid-stimulating hormone. The authors concluded that the study demonstrated that RAI, alone or with PEI, can be considered a valid alternative for TTNs larger than 4 cm when surgery is either refused or contraindicated. PEI plus RAI can be considered when marked shrinkage of a nodule is required or when reduction of the RAI dose can prevent hospitalization.8

Lewis BD et al. (March 2002; Level II-2) conducted an observational study to evaluate the technique, efficacy, and side effects of percutaneous ethanol injection in patients with limited cervical nodal metastases from papillary thyroid carcinoma. Fourteen patients who had undergone thyroidectomy for papillary thyroid carcinoma presented with limited nodal metastases (one to five involved nodes) in the neck between May 1993 and April 2000. Selection criteria were the presence of biopsy-confirmed metastatic papillary thyroid carcinoma in cervical lymph nodes and five or fewer involved lymph nodes that were amenable to percutaneous ethanol injection. Patients had to be poor surgical candidates, to have expressed a preference for no further surgery, or to have been unresponsive to previous radioiodine therapy. Clinical and Sonographic Follow Up was done. All the treated patients received routine clinical and sonographic follow-up every 3 to 6 months. The follow-up period ranged from 2 months to 6 years 5 months (mean, 18 months). Twenty-nine metastatic lymph nodes in our 14 patients were injected. Mean sonographic follow-up was 18 months (range, from 2 months to 6 years 5 months). All treated lymph nodes decreased in volume from a mean of 492 mm3 before percutaneous ethanol injection to a mean volume of 76 mm3 at 1 year and 20 mm3 at 2 years after treatment. Six nodes were re-treated 2-12 months after initial percutaneous ethanol injection because of persistent flow on color Doppler sonography (n = 4), stable size (n = 1), or increased size (n = 1). Two patients developed four new metastatic nodes during the follow-up period that were amenable to percutaneous ethanol injection. Two patients developed innumerable metastatic nodes that precluded retreatment with percutaneous ethanol injection. No major complications occurred. All patients experienced long-term local control of metastatic lymph nodes treated by percutaneous ethanol injection. In 12 of 14 patients, percutaneous ethanol injection was successful in controlling all known metastatic adenopathy. The authors concluded that Sonographically guided percutaneous ethanol injection is a valuable treatment option for patients with limited cervical nodal metastases from papillary thyroid cancer who are not amenable to further surgical or radioiodine therapy.9

Discussion:

Five studies were selected for this review. Levels of evidence were level III for four studies, level I for one of the study. The kinds of studies available for this review were mostly case series including both prospective and retrospective analysis and one of the studies is a randomized comparative study. The studies have evaluated the efficacy of PEI in treating recurrent thyroid cancers, toxic thyroid nodules, cervical nodal metastases from thyroid carcinoma and focal distant metastases of well-differentiated thyroid cancer. One of the studies evaluated its efficacy when administered along with radiofrequency ablation and another study which is a randomized trial compared PEI and radioiodine and radioiodine alone for the treatment for thyroid cancer. One of the studies showed that it can be used as an alternative to surgery and radioiodine therapies and another study showed that this can be used along with radioiodine treatment. Most of the studies evaluated the efficacy of PEI on recurrent thyroid cancers and concluded that it is effective in controlling the recurrent thyroid carcinomas in selected patients who cannot be considered for surgery. All the studies concluded that PEI for thyroid cancer can be a safe non surgical treatment option as an alternative to surgery for those who are poor surgical candidates or contraindicated for surgery. The studies also suggested that there is a need for larger, prospective and long term follow up studies and more evidence to support that PEI is effective in treating thyroid cancers.

Conclusion:

The available data suggests that PEI on thyroid Carcinomas is a non surgical treatment option that helps in controlling recurrent thyroid carcinomas and can be considered as an alternative to surgery for those who cannot be considered for surgery. But the data available for PEI on thyroid carcinomas is limited and of low level evidence and also does not support its effectiveness on a long term basis. Further research and evidence is needed to support the efficiency of PEI in treating thyroid cancers.

Recommendation:

Ethanol Injection for Thyroid Cancer can be considered as Experimental and Investigational as the available evidence is limited and of low level evidence which does not support its effectiveness on a long term basis.

Other Considerations:

However, there is some evidence that suggests that PEI is effective in treating cystic thyroid lesions, particularly recurrent cysts after ruling out the malignancy. As surgical resection is the only preferred treatment option available, PEI may be considered as a non surgical method of treatment alternative to surgery and also when surgery is contraindicated.

References:

What you need to know about Thyroid Cancer. National Cancer Institute. U.S. National Institutes of Health. Available at: http://www.cancer.gov/cancertopics/wyntk/thyroid [Accessed on June 29, 2010]

Percutaneous Ethanol Injection: Images. Kosmix. Available at: http://www.kosmix.com/topic/percutaneous_ethanol_injection/Images# [Accessed on June 29, 2010]

Thyroid Cancer: Overview. Kosmix. Available at: http://www.kosmix.com/topic/Thyroid_cancer [Accessed on June 29, 2010]

Ethanol Injection Helps Thyroid Cancer Patients. Alcohol cut tumor volume 50% in bone metastasis cases where radioiodine was ineffective. ABC news / Health. Available at: http://abcnews.go.com/Health/Healthday/story?id=4507472&page=1 [Accessed on June 29, 2010]

Kim BM, Kim MJ, Kim EK, Park SI, Park CS, Chung WY. Controlling recurrent papillary thyroid carcinoma in the neck by ultrasonography-guided percutaneous ethanol injection. Eur Radiol. 2008 Apr; 18(4):835-42.

Lim CY, Yun JS, Lee J, Nam KH, Chung WY, Park CS. Percutaneous ethanol injection therapy for locally recurrent papillary thyroid carcinoma. Thyroid. 2007 Apr; 17(4):347-50.

Monchik JM, Donatini G, Iannuccilli J, Dupuy DE. Radiofrequency ablation and percutaneous ethanol injection treatment for recurrent local and distant well-differentiated thyroid carcinoma. Ann Surg. 2006 Aug; 244(2):296-304.

Zingrillo M, Modoni S, Conte M, Frusciante V, Trischitta V. Percutaneous ethanol injection plus radioiodine versus radioiodine alone in the treatment of large toxic thyroid nodules. J Nucl Med. 2003 Feb; 44(2):207-10.

Lewis BD, Hay ID, Charboneau JW, McIver B, Reading CC, Goellner JR. Percutaneous ethanol injection for treatment of cervical lymph node metastases in patients with papillary thyroid carcinoma. AJR Am J Roentgenol. 2002 Mar; 178(3):699-704.

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