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[Somayeh khosravi, Shirin Hasani Ranjbar, Sayeh Alizad Jahani. Papillary Thyroid Cancer with diffuse lung metastasis. Electronic Physician, 2012;4(2):555-559. Available at: http://www.ephysician.ir/2012/555-559.pdf ]. (ISSN: 2008-5842). http://www.ephysician.ir

Papillary thyroid carcinoma (PTC) is the most frequent type of thyroid cancer. Recent studies showed that the incidence of PTC is growing ( between 2.7 to 7.7 per 100,000) (1, 2) .Some factors may be responsible for the increased incidence of this tumor. The first is detection of small early lesions by ultrasonography and fine-needle aspiration (FNA). The second is the better recognition of the follicular variant of papillary carcinoma (FVPTC). Other factors include more common exposure to the ionizing radiation and a more iodine rich diet. Of the several histological variants of papillary carcinoma the follicular variant is to be probably most common (accounting for about 10 percent of all PTCs) (3). The overall prognosis for papillary thyroid carcinomas is very good with a 10-year survival rate of 93% (4). Distant metastases which need higher activities of radioiodine are less frequent with 10-20%. Ten percent of patients have metastases beyond the neck at the time of diagnosis. Between such patients 25 percent have skeletal metastases, and 75 percent have pulmonary metastases, but milliary pattern of lung metastasis is very rare in PTC. A specific finding in children is disseminated, milliary lung metastases with intense radioiodine uptake. The 10-year survival rate is 30 to 50 percent. Still higher survival rates have been noted in patients whose pulmonary metastases could be detected by radioiodine imaging (5). Even in advanced cases of childhood thyroid cancer, long-lasting remissions can be achieved. Follicular-variant papillary cancers (FVPTC) are likely to be smaller than common-type papillary cancers, and the risk of regional lymph node metastases may be uncommon (6, 7). One of the differential diagnoses of milliary nodules in lungs is thyroid carcinoma in which, increasing thyroglobulin (Tg) levels and positive radioactive iodine uptake are diagnostic (8). Since the 1940s Radioiodine (131-I) therapy has been used for patients with papillary or follicular thyroid cancer (9). Radioiodine has both scanning and treatment aspects. Patients were treated with 131-I have a five-year survival rate of 60 percent, compared with 30 percent in those whose tumors do not concentrate 131-I (10). Here we report a patient suffering from Papillary Thyroid Cancer with Follicular Variant and milliary lung metastasis at presentation who was treated with radio iodine and discuss the challenging management of such cases.

An 18 year old man presented initially with weight loss (10kg) in two month and a 3 month history of a mass on the right side of his neck, which had recently increased in size. The patient had no past history of neck radiation or a family history of thyroid cancer. The lymph nodes of the lateral compartment of neck were significantly enlarged. Physical examination revealed a palpable firm, fixed mass measuring 3.5×2.5 ×2cm in right lobe. The margins were irregular. The left lobe and the isthmus were soft without any abnormality and two lymph nodes measuring 0.5×0.5 were palpable bilaterally. Chest examination revealed diffuse crackle. Physical examination of other organs was unremarkable. Ultrasonography of thyroid was compatible with an irregular mass in right lobe of thyroid and multiple enlargements of cervical lymph nodes bilaterally.

Fine Needle Aspiration Cytology (FNAC) of right thyroid nodule revealed papillary thyroid carcinoma with follicular variant. Hematologic data including Complete Blood Count (CBC), electrolytes, Blood Urea Nitrogen (BUN), creatinine, Erytrocyte Sedemination Rate (ESR), Fasting Blood Sugar (FBS) were within normal limits. Thyroid function tests revealed the following values: Triiodothyronine (T3): 80µg/dl, Thyroxine (T4): 4.4µg/dl, Thyroid stimulating hormone (TSH): 6.4MIU/L, and Thyroglobulin (Tg) :1090 ng/ml. Total thyroidectomy with central node dissection was conducted and then the patient was treated with 150 mic Radioactive Iodine-131. Levothyroxine sodium (150 microgram daily) was prescribed. Ultrasonography in this stage reported that thyroid tissue and cervical lymph nodes were not seen. After 1 month, he presented to clinic with Tonic-clonic seizure and urine incontinency and laboratory data reported the serum calcium level at 5mg/l.

Brain CT scan for rule out of metastasis was done and reported normal; so according to history of neck dissection and biochemical tests, secondary hypoparathyroidism due to thyroidectomy was diagnosed. Patient underwent treatment whit pearl Rocatrol (6/daily) and Calcium Carbonate (3000 mg/daily). He was discharged with normal serum calcium concentration. After two months, productive cough, dyspnea, orthopnea, and paroxysmal nocturnal dyspnea gradually added to first manifestations and then progressive cyanosis of the lips and fingers was appeared. Chest x ray showed infiltrated nodular snow storm viewed (figure 1). In HRCT scan with contrast there was innumerable small parenchymal nodular lesions (Figure 2). However, considering diffuse milliary pattern at both lungs witch mostly suggested milliary tuberculosis; broncoscopy with alveolar lavage was done that was negative for tuberculosis and also no fungal or other micro-organisms were detected.



Figure 2. Spiral HRCT with contrast: innumerable small parenchymal nodular

Echocardiography was unremarkable but mild pericardial effusion was detected and pulmonary artery pressure (PAP) was 20mmHg. In this regard, pulmonary function tests (PFT) was done that reported: FEU: 41%, FEV1/FVC: 83%. Pulmonary embolus was ruled out by pulmonary ventilation/perfusion scan. Retrospectively post radio iodine ablation scan revealed, increasing uptake in both lungs and confirmed iodine avid thyroid tumor metastasis.

Based on consultation with respiratory service radioiodine (I-131) therapy with dosimetry was recommended for him. According to the documentation provided Respiratory distress in the field of Pulmonary metastasis was enhanced against other differential diagnosis such as (pulmonary fibrosis), in this regard radioiodine (I-131) therapy with 170 mic was done. After 3 days increasing uptake in lungs was reported in post ablation scan. On the other hand Tg level was more than 1000ng/ml. The patient was treated with Levothroxine sodium (1/5 daily) and after six months, respiratory symptoms declined and the patient was ready to receive the next dose of radioiodine therapy.
3. Discussions

According to latest edition of American Thyroid Association (ATA), PTC has 15 variants. The follicular variant of papillary carcinoma (FVPTC) is the most frequent type of PTC witch firstly described by Hazard and Crile in 1953 who named this lesion alveolar variant of PTC (11). From time to time, patients present with metastasis in a neck lymph node or with hoarseness of voice caused by involvement of the recurrent laryngeal nerve. Infrequently, FVPTC gives rise to lung metastases in the nonexistence of lymph node involvement (12). Conversely, follicular thyroid cancer showed more distant metastases than papillary thyroid cancer (13, 14).

Follicular carcinoma and follicular adenoma are main differential diagnoses of this tumor. FVPTC may show partially or completely encapsulated (15, 16) in relation to pure papillary thyroid carcinoma, difficulties in pre-operative diagnosis and high ratios of first clinical presentation with distant metastases were the main problems to be conquer (17).

In same case report that Owned to a 10 year-old-boy with pulmonary metastases under taken thyriodectomy and has received two doses of ablative therapy and improved. Thyroglobin levels and his general condition were good after ablative therapy (18). There are case reports of this entity in literature presenting as lung metastasis.

According to American Thyroid Association Guidelines these macronodular pulmonary metastases may be treated with RAI if demonstrated to be iodine avid (19). Complete remission is not common and survival remains poor. To manage and confirm lung metastasis in such cases beside evaluation of tuberculosis and other infections, considering iodine avidity and thyroglubolin levels are critical. In this situation, pulmonary fibrosis may be a severe side-effect and the indication for repeated courses of radioiodine therapy has to be decided thoroughly (20). In follow up thyroglobulin level and the size of pulmonary nodules could be helpful for differentiating active lung metastasis from fibrosis to decide for repeated Radi iodine ablation.
Acknowledgements:

The authors thank the Endocrionology & Metabolism research Institute of Tehran University of Medical Sciences, for their support and contribution to this study.

Dr. Shirin Hasani Ranjbar

Endocrinology and Metabolism Research Center

Shariati Hospital, Tehran, Iran

Tel: +98.2188220037

Fax: +98.2188220052

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[Suresh Kumar Rathi, Sandip Shah. Evidence Based Education System (EBES): Our Achievements and way forward. Electronic Physician, 2012;4(2):560-564. Available at: http://www.ephysician.ir/2012/560-564.pdf ]. (ISSN: 2008-5842). http://www.ephysician.ir

Nintheenth century was the century of Prevention and Public Health (Water and sanitation and hygiene), 20^th century was of Antibiotics /chemotherapy /drug development (early diagnosis and prompt treatment) and 21^st century is of innovation, knowledge and knowledge translation into practice through sufficient evidences. Over the past few years there has been a paradigm shift in the way education system has evolved in many affluent countries (1, 2). There has been a shift in terms of both teaching system and curriculum (3). Till date Medical Educators used to teach as they have been taught (4). No formal training programs for educators existed. The teaching crisis we face today is the direct result of the divorce between theory and practice. As Singh et al highlighted the role of Medical Education Unit (MEU) in faculty development⁴ and also in India every medical college is supposed to have Medical Education Unit, the ground realty is that it is non-functioning in most of the medical colleges. Hence by default it is assumed that doctors are good teachers and time and experience can augment teaching skills and methodologies further (5). However, in fast moving era, the entire system has changed in many parts of the world (6). In India; even today a large number of the doctors working as faculty in medical colleges are not really trained to teach. This is exactly where the Evidence Based Education System (EBES) comes to help medical educators and also it is the need of hour. EBES is the integration of professional wisdom with the best available empirical evidence in making decisions about how to deliver instructions. To put it into a simpler way; teachers opting for methods of teaching that consistently proved more effective than other teaching techniques. Professional wisdom achieved through individual experience and consensus opinion while empirical evidence is achieved through scientifically sound research. Without integration of both (professional wisdom and best evidence), medical education cannot adapt to local circumstances and even cannot operate efficiently where research evidence is absent or incomplete. If we want to understand the nitty-gritty of EBES then we have to understand different teaching methodologies. The different teaching methods are:

1. 
   One way Teaching Methods: (Instructor Dominated Methods)
   
   1. 
      Lecture
      
   2. 
      Resource person’s presentation
      
   3. 
      Symposium
      
2. 
   Two Way Teaching Methods: (Learner Dominated Methods)
   
   1. 
      Case Study
      
   2. 
      Problem Based Learning
      
   3. 
      Group Discussion
      
   4. 
      Role Play
      
   5. 
      Brain Storming Sessions
      
   6. 
      Demonstrations
      
   7. 
      Tours and Field Trips
      
   8. 
      Learning by Teaching / Doing
      
   9. 
      Collaboration (Group Work)
      
   10. 
       Workshops
       
   11. 
       Seminars
       
   12. 
       Evidence Based Medicine/Dentistry
       
   13. 
       Evidence Based Practice
       
3. 
   Teaching through computer (e-learning) / Lab Work Methods
   

Here, in Sumandeep Vidyapeeth (SV) – a deemed to be university, we are extraordinarily fortunate as Medical Educators to have a Sumandeep as our home of EBES which guides us as we begin to transform our curricula to train morrow’s doctors. We have adapted Evidence Based Medicine (EBM) and Evidence-Based Practice (EBP) as new teaching methodology for undergraduates. EBM is the reliable, explicit, and judicious use of the best current evidence in making decisions about the care of individual patients (7). In other words it is the process of systematically reviewing, appraising and using clinical research findings to aid the delivery of optimum clinical care to patients (8). While EBP is a process of care that takes the patient and his or her preferences and actions, the clinical setting including the resources available, and current and applicable scientific evidence, and knits the three together using the clinical expertise and training of the health-care providers (9).

We have adopted EBES on January 23, 2007 and decided to implement it in phase wise manner.

A University Core Committee for EBES constituted in February 2007 followed by EBES Dental College Core Committee which implemented EBE in Dental College by organizing faculty lecture series. In same way in October 2007, SBKS Medical Institute and Research Centre EBES Core Committee formed which organized lecture series in December 2007 to January 2008. In April 2008, SBKS Medical Institute and Research Centre Curriculum Core Committee were formed. University Research Cell was established in the month of June 2008. In the next month, i.e., July 2008 EBE curriculum core committee for Physiotherapy College formulated. In the month of April 2009, SBKS Medical Institute and Research Centre finalized EBM curriculum.

In May 2009, 6 faculty members deputed for advance training of Ethics in Medical Research organized by Indian Institute of Public Health-Gandhinagar. In June 2009, EBES Curriculum Committee for Allied Sciences constituted which adopted and implemented the EBE curriculum in March 2010. In first quarter of 2010, EBES lecture series for faculty was organized. In April 2010, EBES adopted and implemented by constituent institutes of SV (SBKS Medical Institute and Research Centre, Physiotherapy, Nursing, Pharmacy and Management). In October 2010, SV constituted EBES newsletter editorial board. A series of meeting were held during 18-20 October, 2010 with nursing faculty of University of Hull, UK for evidence based nursing education system.

A State level conference on evidence based nursing education system was organized in the month of October 4^th-5^th, 2010. SV-EBES core committee including authors deputed for training at first international workshop in India on “How to teach EBM” during November 24-27, 2010. Second round of EBES lecture series for faculty and also two EBES workshop for nodal, departmental coordinators and faculty members were organized during December 2010 – October 2011. An international conference and workshop on EBES were organized in the month of March 2011.

Phase III also comprises of review of EBE curriculum for undergraduates, feedback from all stakeholders for acceptability, ease, advantages of EBE curriculum over traditional curriculum, and development of PG curriculum with re-assessment.

The process of development of EBE curriculum and implementation of EBE system in our university is presented as following: