PROTOCOL OF THE PROSPECTIVE RANDOMIZED STUDY FOR THE USE OF AUTOFLUORESCENCE IN THYROID SURGERY - PARFLU STUDY.
Patients’ criteria for inclusion or exclusion
- All patients over 18 years old undergoing thyroidectomy are included, with or without lymph node dissection, if they consent.
- The categories of patients that are excluded are:
- Patients undergoing reoperations.
- Patients undergoing lobectomy or subtotal thyroidectomy.
- Patients suffering from hyperthyroidism of any etiology.
- Patients undergoing simultaneous parathyroidectomy for primary, secondary or tertiary hyperparathyroidism with the thyroidectomy
Two groups of 200 patients will be created; one group where autofluorescence will be used for detecting parathyroid glands, and one where there will be only visual identification of parathyroid glands.
- The inclusion of patients will be random after using an algorithm created by computer software. Nor the patient or the doctors will be able to choose.
Patient consent and information – information on side effects
- All patients who meet the inclusion criteria will be informed in detail about the existence of the study and its objectives.
- They will be informed of the random selection.
- They will be informed about the type of technology that will be used intraoperatively if they are selected.
- They will be informed that:
- It is not an interventional method and does not affect their health.
- There is not any ionizing radiation in this technology.
- The time of the surgery will be not increased.
Finally, they will sign the consent form if they want to participate or not in the study.
Parameter measurement
- The laboratory tests that will be used to extract results are those that our Department uses as a routine and are included in the preoperative and postoperative examination of our patients; this means that there will be no new charge, and are the following:
- Preoperatively: Blood test for measurement of total Calcium (Ca ), serum albumin ( Alb ), Phosphorus ( P ), serum parathormone ( PTH ), 25-hydroxyvitamin- D.
- Immediately postoperatively: Ca and PTH (by blood test)
- At 1st postoperative day: Ca, Alb, P, PTH (by blood test)
- A criterion of hypoparathyroidism on the first postoperative day will be the fall of PTH in values below the normal range in our laboratory or the presence of symptomatic hypocalcaemia.
Patients will initially be classified into two categories:
- Those who do not have postoperative abnormal PTH levels and no symptoms of hypocalcaemia.
- Those who have postoperative PTH levels below the normal range and/or have low levels of (albumin-corrected) calcium and clinical signs of hypocalcaemia.
Group 1 patients will not receive calcium replacement therapy, while group 2 patients will receive calcium replacement therapy.
The calcium replacement therapy consists of per os administration of calcium and vitamin D.
- Patients will be classified at the 1 the postoperative week into two categories:
Category A:
patients with no signs from the blood test results of postoperative hypocalcaemia or postoperative hypoparathyroidism
Category B:
patients with signs from the blood test of postoperative hypocalcaemia.
Group B patients will be classified into two subcategories:
B 1. Patients with temporary postoperative hypocalcaemia or temporary postoperative hypoparathyroidism.
B 2. Patients with permanent postoperative hypocalcaemia or permanent postoperative hypoparathyroidism.
- For proper classification, patients should undergo calcium homeostasis blood tests (Ca , P , PTH , Alb ) one week after surgery. Preferably the repeated blood tests will be done in our Hospital (as is already done now in our patients), but if this is difficult for the patient for practical reasons, the blood tests can take place at another laboratory. The normal range of the results will be considered the range of each laboratory.
- After the 1st week’s blood tests examination, patients who belong to category A will be exempted from additional reassessment.
- Patients will belong to category B will undergo new revaluations (laboratory Recheck by their endocrinologist, telephone communication), the final assessment six months after surgery.
- After the end of the semester, patients, depending on whether they need calcium and vitamin D replacement, will be classified as mentioned in the two final categories:
B1. Patients with temporary hypoparathyroidism (Discontinuation of treatment within six months)
B 2. Patients with permanent hypoparathyroidism (Continuation of treatment after six months).
- Analysis of the parameters and extraction of results and conclusions will follow.
It should be noted that the above procedure is followed for several years in our Department and has not been modified to a minimum by the prospective PARFLU study.
Description of Autofluorescence Technique
Autofluorescence in surgery is a method that uses imaging technology using special cameras, light sources, filters, and software to generate near infrared (infra – red ) light to distinguish the tissue in the surgical field. It is a technology that has been used in recent years in many surgical specialities.
In recent years it has been used in thyroid surgery, where it helps to distinguish the parathyroid glands.
For our study, we will use a camera system, power sources, software and monitor, which are already available in our operations. The system is the VIRON XMAXER ENDOSCOPY GmbH.
During the operation, at selected surgical times, the surgeon in charge holds the special camera with the light source, covered by a sterile cover, at a distance of about 15 cm from the field. The light source emits almost infrared light (safe for the eyes) at a wavelength of about 750 nm, which is directed to the tissues. The parathyroid glands show the ability of autofluorescence when they receive light at this wavelength, i.e., they emit light at a wavelength of about 810-870 nm. The camera detects light in this spectrum, so the parathyroid glands are distinguished from the surrounding tissues. The screen displays three images: one white light, one of autofluorescence (black and white) and one that composes the two above. In the latter two, the parathyroid gland can be distinguished in the surgical field. The whole procedure does not take more than 30 seconds at a time, which means the total time of the operation is not substantially extended.
The images are recorded and stored in a separate electronic file per patient, and at the end of the operation, the number of parathyroid glands identified by this method will be recorded as well as the number of parathyroid glands visually identified by the surgeon in cases where the method of autofluorescence will not be used.
- To what extent does this technology serve to reduce the rate of temporary postoperative hypocalcaemia or temporary postoperative hypoparathyroidism (B1).
- To what extent does this technology serve to reduce the rate of permanent postoperative hypocalcemia or permanent postoperative hypoparathyroidism (B2).
- If the number of parathyroid glands identified in each patient by the method of autofluorescence has an impact on the incidence of transient or permanent postoperative hypoparathyroidism (B1, B2).
- If the identification of parathyroids by the method of autofluorescence is superior to their visual recognition by the surgeon.
- During the study, natural new questions or data may emerge, which will also be studied.
The Principal Investigator of the Protocol
Dr Kyriakos Vamvakidis
