Synergistic interactions of essential oil components with antibiotics against multidrug-resistant Corynebacterium striatum.

AIM: In this study, it was aimed to examine the antibacterial activity of the essential oil components (EOCs), carvacrol (CAR), cinnamaldehyde (CIN), thymol (TH), alpha pinene (α-PN), eucalyptol (EU), limonene (LIM), and the antibiotics, linezolid (LZD), vancomycin (VAN), gentamicin (GEN), ciprofloxacin (CIP), clindamycin (CLN), and penicillin (PEN) against 50 multidrug resistant Corynebacterium striatum strains, and the synergistic interactions of CAR and CIN with the antibiotics against 10 randomly selected Coryne. striatum strains to explore synergistic interactions to determine if their combined use could enhance antibiotic activity and potentially reduce resistance. METHODS AND RESULTS: The activity of the EOCs and the antibiotics against Coryne. striatum strains isolated from clinical specimens, was examined by broth microdilution method. The synergistic interactions of the EOCs with the antibiotics against 10 randomly selected Coryne. striatum strains were determined by checkerboard method. EOCs, CIN, and CAR and antibiotics, LZD, VAN, GEN, CIP, and CLN were detected to have antibacterial activity against Coryne. striatum strains alone and either synergistic interactions were observed in combinations of the antibiotics with EOCs. CONCLUSIONS: All Coryne. striatum strains were determined to be susceptible to VAN and LZD and resistant to GEN, PEN, CIP, and CLN. Synergistic interactions were observed in all combinations of antibiotics tested with CAR and CIN.

A unique complication of thyroidectomy for Hashimoto's thyroiditis: central retinal artery thrombosis.

BACKGROUND: Central retinal artery occlusion (CRAO) is a rare ophthalmological emergency and also a unique complication after thyroid surgery. METHODS: We present the first case of CRAO following thyroid surgery in a patient with Hashimoto's thyroiditis, along with a variety of interventions to overcome this complication. RESULTS: A 42-year-old female patient suffering from sudden vision loss following total thyroidectomy was diagnosed with CRAO. Hyperbaric oxygen therapy was started within the postoperative first 6 hours. CONCLUSION: Although it is extremely rare, it should be noted that patients may experience retinal artery occlusion following the thyroid surgery. Immediate evaluation of patients with visual impairment in the early postoperative period, and planning of emergent hyperbaric oxygen therapy for the management are critical.

Intraoperative cricothyroid muscle electromyography may contribute to the monitorization of the external branch of the superior laryngeal nerve during thyroidectomy.

Background: In thyroid surgery, both the recurrent laryngeal nerve (RLN) and external branch of the superior laryngeal nerve (EBSLN) should be preserved for maintaining the vocal cord functions. We aimed to evaluate whether EMG of the CTM applied after the superior pole dissection provided additional informative data to the IONM via ETT or not, regarding the EBSLN function. Methods: The prospectively collected data of the patients, who have undergone thyroidectomy with the use of IONM for the exploration of both the RLN and EBSLN between October 2016 and March 2017, were evaluated retrospectively. Patients over 18 years of age with primary thyroid surgery for malignant or benign thyroid disease, and whom were applied CTM EMG with a needle electrode after the completion of thyroidectomy were included in the study. In the study, each neck side was evaluated as a separate entity considering the EBSLN at risk. Results: The data of 41 patients (32 female, 9 male) (mean age, 46.7 + 9.1; range, 22-71) were evaluated. Sixty seven EBSLNs out of 26 bilateral and 15 unilateral interventions were evaluated. With EBSLN stimulation after the superior pole dissection, positive glottic EMG waveforms via ETT were obtained in 45 (67.2%) out of 67, and the mean glottic amplitude value was 261 + 191 µV (min-max: 116-1086 µV). Positive EMG responses via the CTM EMG were achieved from all of the 67 EBSLNs (100%) with stimulation using a monopolar probe at the most cranial portion above the area of divided superior pole vessels. The mean value of CTM amplitudes via CTM EMG obtained with EBSLN stimulation was 5268 + 3916 µV (min-max:1215 -19726 µV). With EBSLN stimulation, the mean CTM EMG amplitude was detected significantly higher than the mean vocal cord amplitude (p<0.0001). The CTM EMG provided more objective quantifiable data regarding the EBSLN function (100% vs 67,2%, p<0.001). Conclusion: In addition to the IONM via ETT, intraoperative post-dissection CTM EMG via needle electrode is a safe, simple and applicable method that may provide significant additional informative data to IONM with ETT by obtaining and recording objective quantitative data related to the EBSLN function.

Comparison of transoral endoscopic thyroidectomy vestibular approach and open conventional thyroidectomy regarding inflammatory responses, pain, and patient satisfaction: a prospective study.

Introduction: The application of transoral endoscopic thyroidectomy vestibular approach (TOETVA) is becoming widespread throughout the world. We primarily aimed to evaluate the severity of surgical trauma in TOETVA and conventional open thyroidectomy (COT) regarding the inflammatory response including the comparison of surgical stress markers [interleukin-6 (IL-6), C-reactive protein (CRP), white blood cell (WBC)]. Material and method: This non-randomized prospective study enrolled two groups with 20 patients each: COT group and TOETVA group. Patients aged 18-65 years with benign thyroid disease; with fine needle aspiration biopsy results of Bethesda III, IV or Bethesda V, VI (<1 cm nodule); thyroid volume <50 cm3; nodule diameter <4 cm; female gender without a previous neck, chin, and/or oral surgery; without vocal cord paralysis preoperatively; and patients in euthyroid state were enrolled to the study. Preoperative, postoperative second hour, first day, and second day CRP, WBC, and IL-6 levels were evaluated. Pain intensity was evaluated with the visual analog scale (VAS) score on the 2nd and 12th hour, 1st and 2nd days postoperatively. Results: All the patients were female and mean age was significantly higher in the COT group. The operative time was significantly longer in the TOETVA group. No significant difference was found between the two groups regarding IL-6 levels. In the TOETVA group, postoperative second hour WBC value (p = 0.044) and first (p = 0.002) and second day (p = 0.005) CRP values were significantly higher. In the TOETVA group, the lower lip and lower chin VAS scores were significantly higher at 2nd and 12th hour, on the first and second days. The anterior neck VAS score was significantly higher in the TOETVA group at the second hour (p = 0.025). General and cosmetic satisfactions were similar at the 15th and 30th days in both groups. Conclusion: The longer operative time and higher postoperative CRP level and VAS score in the chin and lower lip in the TOETVA group suggested that the method is not a minimally invasive technique compared to COT. However, the presence of similar total complication rates and early postoperative general and esthetic satisfaction that improves over time in both groups suggests that the clinical effect of increased magnitude of systemic inflammatory response in TOETVA might be temporary and acceptable.

The Role of 4D-CT for Pre-Operative Localization in Patients with Primary Hyperparathyroidism with Negative Ultrasonography and/or Sestamibi SPECT/CT.

Objectives: The major cause of primary hyperparathyroidism (pHPT) is parathyroid adenoma. Today, minimally invasive parathyroidectomy (MIP) has become the standard treatment for patients in whom the pathological gland can be localized with pre-operative imaging methods. In this study, we aimed to evaluate the role of 4D-CT in pre-operative localization in patients with pHPT who are negative for ultrasonography (USG) and/or sestamibi single-photon emission computed tomography/CT (SPECT/CT) and will undergo primary surgery. Methods: Patients whom were operated between 2018 and 2023 were included to this study. 4D-CT results of patients with one- or two-negative USG and SPECT/CT results were evaluated retrospectively. Results: In this study, 19 patients (5 men and 14 women) with a mean age of 57.1±8.5 years were evaluated. Pathology results were consistent with parathyroid adenoma in 18 patients (94.7%) and parathyroid hyperplasia in 1 patient (5.3%). USG was negative in six patients, SPECT/CT was negative in 14 patients, and both were negative in four patients. In 4D-CT, positive images were detected in 15 patients and these results were finalized as true positive in 14 patients and false positive in 1 patient. The sensitivity of 4D-CT was 82.4% (95% CI: 60.4-95.3%), positive predictive value was 93.3% (95% CI: 73.8-99.6%), accuracy was 78.9%, and localization rate was 73.7%. In 14 (73.7%) patients, the pathological glands were removed by MIP. Conclusion: In approximately 75% of patients with negative USG and/or SPECT/CT, the pathological gland can be localized with 4D-CT and MIP can be applied in these patients.

Persistent and Recurrent Primary Hyperparathyroidism: Intraoperative Supplemental Methods, Basic Principles of Surgery, and Other Treatment Options.

Reoperative parathyroid surgery is challenging even for experienced surgeons. Cure rates are lower than primary surgery. Good anatomical and embryological knowledge is important. Preoperatively, a comprehensive surgical strategy should be planned. Pre-operative imaging modalities should be used extensively to find the overlooked gland to have a possibility to perform focused parathyroid surgery to avoid possible complications. One of the important developments is the new ancillary methods to find overlooked parathyroid glands. Orthotopic and possible ectopic locations should be known well by the surgeon to increase the surgical success rate. Reoperative parathyroid surgery needs a distinctive approach compared to primary parathyroid surgery. Basic principles include the selection of the incision and route for entering the thyroid region, use of ancillary methods, and intraoperative nerve monitoring and also require a meticulous dissection. Obtaining a surgical cure is difficult and high surgical caution is needed. Post-operative complication rates are higher compared to primary parathyroid surgery. Other treatment methods and medical treatment options may be evaluated in a patient who cannot undergo surgery.

Predictive Factors Affecting the Development of Lateral Lymph Node Metastasis in Papillary Thyroid Cancer.

Objectives: Lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC) determines the extent of surgery to be performed and the prognosis of the disease. In this study, we aimed to evaluate the clinicopathological risk factors affecting the development of LLNM. Methods: We retrospectively evaluated the demographic and clinicopathological data of 346 cases with PTC who were operated in our clinic between May 2012 and September 2020. The patients were divided into 2 groups as patients with LLNM (Group 1) and without LLNM (Group 2). Results: Thirty-six (10.4%) patients out of 346 patients with PTC had LLNM. A statistically significant difference was found between Group 1 and Group 2 regarding the male gender (M/F: 38.9% vs. 21.6%; p=0.020), tumor size (2.30±1.99 cm vs. 1.31±1.40 cm; p=0.000), lymphovascular invasion (69.4 vs. 20.6%; p=0.000), multicentricity (69.4% vs. 35.5%; p=0.000), multifocality (p=0.000), aggressive variant (22.2% vs. 9.4%; p=0.000), extrathyroidal extension (50% vs. 16.1% p=0.000), central lymph node metastasis (CLNM) rates (75% vs. 6.5%; p=0.000), and ≥3 cm lymph node metastasis (48.5% vs. 0%, p=0.000), distant metastasis (2.1% vs. 0%, p=0.000), respectively. Multivariance analysis determined the presence of CLNM as an independent risk factor for the development of LLNM. Conclusion: The presence of CLNM in patients with PTC was determined as an independent risk factor for the development of LLNM. Although there has been increasing debate about prophylactic central neck dissection (pCND) in LLNM, pCND should still be considered in these patients as the rate of CLNM is high in patients with LLNM. CLNM might be a reference for surgeons to determine the extent of surgery. In addition, the presence of CLNM is important for close follow-up for the early detection of LLNM recurrence.

Management of Thyroid Nodules.

Thyroid nodules are common and the prevalence varies between 4 and 7% by palpation and 19-68% by high-resolution USG. Most thyroid nodules are benign, and the malignancy rate varies between 7 and 15% of patients. Thyroid nodules are detected incidentally during clinical examination or, more often, during imaging studies performed for another reason. All detected thyroid nodules should be evaluated clinically. The main test in evaluating thyroid function is thyroid stimulating hormone (TSH). If the serum TSH level is below the normal reference range, a radionuclide thyroid scan should be performed to determine whether the nodule is hyperfunctioning. If the serum TSH level is normal or high, ultrasonography (US) should be performed to evaluate the nodule. US is the most sensitive imaging method in the evaluation of thyroid nodules. Computed tomography (CT) and magnetic resonance imaging are not routinely used in the initial evaluation of thyroid nodules. There are many risk classification systems according to the USG characteristics of thyroid nodules, and the most widely used in clinical practice are the American Thyroid Association guideline and the American College of Radiology Thyroid Imaging Reporting and Data System. Fine needle aspiration biopsy (FNAB) is the gold standard method in the evaluation of nodules with indication according to USG risk class. In the cytological evaluation of FNAB, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the most frequently applied cytological classification. TBSRTC is a simplified, 6-category reporting system and was updated in 2023. The application of molecular tests to FNAB specimens, especially those diagnosed with Bethesda III and IV, is increasing to reduce the need for diagnostic surgery. Especially in Bethesda III and IV nodules, different methods are applied in the treatment of nodules according to the malignancy risk of each category, these are follow-up, surgical treatment, radioactive iodine treatment, and non-surgical ablation methods.

[Investigation of the Efficacy of Cinnamaldehyde, Cannabidiol and Eravacycline in a Malaria Model]. / Sitma Modelinde Cinnamaldehyde, Cannabidiol ve Eravacycline'in Etkinliginin Arastirilmasi.

In this study, it was aimed to investigate the antimalarial activity of cinnamaldehyde (CIN) and cannabidiol (CBD) which have shown various biological activities such as potent antimicrobial activity and eravacycline (ERA), a new generation tetracycline derivative, in an in vivo malaria model. The cytotoxic activities of the active substances were determined by the MTT method against L929 mouse fibroblasts and their antimalarial activity were determined by the four-day test in an in vivo mouse model. In this study, five groups were formed: the CIN group, the CBD group, the ERA group, the chloroquine group (CQ) and the untreated group (TAG). 2.5 x 107 parasites/mL of P.berghei-infected erythrocyte suspension was administered IP to all mice. The determined doses of active substances were given to the mice by oral gavage in accordance with the four-day test and the parasitemia status in the mice was controlled for 21 days with smear preparations made from the blood taken from the tail end of the mice. The IC50 values, which express the cytotoxic activity values of the active substances were determined as 27.55 µg/mL, 16.40 µM and 48.82 µg/mL for CIN, CBD and ERA, respectively. The mean parasitemia rate in untreated mice was 33% on day nine and all mice died on day 11. On the ninth day, when compared with the TAG group, no parasites were observed in the CIN group, while the average parasitemia was 0.08% in the CBD group and 17.8% in the ERA group. Compared to the mice in the TAG group, the life expectancy of the other groups was prolonged by eight days in the CIN group, 12 days in the CBD group and eight days in the ERA group. It has been determined that all three active subtances tested in this study suppressed the development of Plasmodium parasites in an in vivo mouse model and prolonged the life span of the mice. It is thought that the strong antimalarial activity of CIN and CBD shown in the study and the possible positive effect of ERA on the clinical course can be improved by combining them with the existing and potential antimalarial molecules.

Application of scanning acoustic microscopy for evaluation of MMP activation in multiple cancer cell lines with a smart probe.

Background/aim: Matrix metalloproteinases (MMPs) play an important role in the evaluation of many cancer types; however, the detection usually presents a challenge. Further assays for a better understanding of the fundamental roles of MMPs in pathophysiology are still needed. We aimed to use an activatable probe in scanning acoustic microscopy (SAM) to evaluate acoustically if the probe can aid the visualization of the effects of in vitro MMP activity. Materials and methods: We applied scanning acoustic impedance microscopy to obtain acoustic impedance maps of the cell line models of HT1080, THP-1, and SK-MEL-28 with and without MMPSense 680 probe incubation. We visually validated our results using confocal laser scanning microscopy imaging. We further analyzed the effects of MMPSense 680 probe on cell viabilities to eliminate any artifacts. Results: This is the first study presenting the applicability of SAM in the acoustical evaluation of MMPSense 680 probe cleavage in a cellular medium through acoustic impedance measurements. We proposed that SAM measurement with the activatable probe can be used as an effective tool for studying the acoustical variations of MMP activities in cell lines. As a result, we detected MMPSense 680 probe cleavage in HT1080 human fibrosarcoma cell line. Conclusion: We showed that SAM with the smart probe can detect proteolytic activity using MMPSense 680 in in vitro HT1080 cell line by acoustic impedance measurements. SAM could be proposed as an alternative tool leading a novel way for a better understanding of the roles of MMPs in cancer progression before clinical settings.

An unusual finding after adrenal surgery: a case series of adrenal schwannomas.

Adrenal schwannomas are rare benign tumors with no specific imaging and laboratory findings to diagnose preoperatively. Due to the limited number of cases in the literature, clinical, imaging, and pathological findings are presented in this study. Case 1 is a 61-year-old woman patient who has a 31-mm mass in the right adrenal gland. This mass was nonfunctional; in imaging studies, this mass had a cystic necrotic component, and high 18-fluorodeoxyglucose (FDG) uptake was seen. There was no metaiodobenzylguanidine (MIBG) uptake. Laparoscopic transabdominal right adrenalectomy was performed, and the pathology result was consistent with adrenal schwannomas. Case 2 is a 63-year-old man patient who presented with a 38-mm mass in the left adrenal gland. This mass was nonfunctional and similar to that in Case 1; this mass had a cystic component. Laparoscopic transabdominal left adrenalectomy was performed. The diagnosis of adrenal schwannoma with degeneration was revealed. Case 3 was a 72-year-old woman patient admitted to the hospital for a 125-mm left adrenal mass. Similar to Case 1, this mass also had a cystic necrotic component in imaging studies. High FDG uptake was seen, and the patient underwent conventional adrenalectomy due to the suspicion of malignancy. After pathological evaluation, a diagnosis of adrenal schwannoma was made. A main diagnostic challenge in adrenal schwannomas is the preoperative diagnosis. These masses have no pathognomonic finding or specific hormonal function. Imaging findings of these masses may increase the suspicion of malignancy, which may affect decisions for surgery and the surgical technique.

Persistent and Recurrent Primary Hyperparathyroidism: Etiological Factors and Pre-Operative Evaluation.

Primary hyperparathyroidism (pHPT) is the most common cause of hypercalcemia and currently the only definitive treatment is surgery. Although the success rate of parathyroidectomy is over 95% in experienced centers, surgical failure is the most common complication today. Persistent HPT (perHPT) is defined as persistence of hypercalcemia after parathyroidectomy or recurrence of hypercalcemia within the first 6 months, and recurrence of hypercalcemia after a normocalcemic period of more than 6 months is defined as recurrent HPT (recHPT). In the literature, perHPT is reported to be 2-22%, and the rate of recHPT is 1-15%. perHPT is often associated with misdiagnosed pathology or inadequate resection of hyperfunctioning parathyroid tissue, recHPT is associated with newly developing pathology from potentially pathologically natural tissue left in situ at the initial surgery. In the pre-operative evaluation, the initial diagnosis of pHPT and the diagnosis of perHPT or rec HPT should be confirmed in patients who are evaluated with a pre-diagnosis (suspect) of perHPT and recHPT. Surgery is recommended if it meets any of the recommendations in surgical guidelines, as in patients with pHPT, and there are no surgical contraindications. The first preoperative localization studies, surgical notes, operation drawings, if any, intraoperative PTH results, pathological results, and post-operative biochemical results of these patients should be examined. Localization studies with preoperative imaging methods should be performed in all patients with perHPT and recHPT with a confirmed diagnosis and surgical indication. The first-stage imaging methods are ultrasonography and Tc99m sestamibi single photon tomography Tc99mMIBI SPECT or hybrid imaging method, which is combined with both single-photon emission computed tomography and computed tomography (SPECT/CT). The combination of USG and sestamibi scintigraphy increases the localization of the pathological gland. In the secondary stage, Four-Dimensional computer tomography (4D-CT) or dynamic 4-dimensional Magnetic Resonance Imaging (4D-MRI) can be applied. It is focused on as a secondary stage imaging method, especially when the lesion cannot be detected by conventional methods. Positron Emission Tomography (PET) and PET/CT examinations with 11C-choline or 18F-fluorocholine are promising imaging modalities. Invasive examinations can rarely be performed in patients in whom suspicious, incompatible or pathological lesion cannot be detected in noninvasive imaging methods. Bilateral jugular vein sampling, selective venous sampling, parathyroid arteriography, imaging-guided fine-needle aspiration biopsy, and parathormone washout are invasive methods.

The Relationship of Negative Imaging Result and Surgical Success Rate in Primary Hyperparathyroidism.

Objectives: In present, the effect of pre-operative negative imaging results on surgical outcomes of primary hyperparathyroidism (pHPT) is still controversial. In this study, we aimed to evaluate the effect of pre-operative imaging on surgical outcomes. Methods: The data of pHPT patients who were operated between 2009 and 2018 were evaluated retrospectively. Patients were divided three groups according to scintigraphy and/or ultrasonography results: Group 1; both imaging positive, Group 2; single imaging positive, and Group 3; patients in whom both imaging modalities are negative. Pre-operative biochemical characteristics, parathyroid pathologies, diameter and volume of the pathological gland, surgery rates, persistence, and recurrent disease rates of the groups were compared. Results: Of 311 patients (258F, 53M) with a mean follow-up period of 24.7±18 months and a mean age of 54.1±12.9 years; 161 were in Group 1, 111 were in Group 2, and 39 were in Group 3. The diameter of pathological gland (2.1±0.8, 1.6±0.9, 1.5±0.7 cm; p<0.001; in Group 1,2,3 respectively) and the volume of pathological gland (2±3.2, 1.4±2.9, 1.1±2.2 cm3; p<0.001; in Group 1,2,3, respectively) in Group 1; the rate of multi gland disease (5.7%, 11%, 21%; p=0.024; in Group 1, 2, 3, respectively) in Group 3 were significantly higher. In the 1, 2, 3 group; bilateral exploration rates were 93.2%, 48.6%, and 5.1%, and focused surgery or unilateral exploration rates were 6.8%, 51.4%, and 94.9%, respectively, with a significant difference (p<0.001). After the first surgery, the cure rate was 91.3%, 93.7%, and 89.7%, and the persistent patient rate was 7.5%, 3.6%, and 10.3% in Groups 1,2,3, respectively, and there was no significant difference. At the end of the follow-up period after secondary intervention applied in persistent and recurrent patients, the overall cure rate was 97.4%, 96.4%, and 97.4%, persistent disease rate 1.3%, 1.8%, and 2.6%, recurrent disease rate 1.3%, 1.8%, and 0%, respectively. Conclusion: In imaging-negative patients with pHPT, the possibility of multi gland disease and smaller pathological glands should be considered at the time of surgery. Surgery in imaging-negative patients can be performed with a similar and acceptable cure rate to imaging-positive patients.

Congenital diaphragmatic hernia with gastric perforation in adult: Intrathoracic gastric perforation.

Congenital diaphragmatic hernias are rarely seen and they are usually diagnosed in the neonatal period. Congenital diaphragmatic de-fect, also known as Bochdalek hernia, usually occurs with the persistence of the pleuroperitoneal canal in the left posterolateral region of the diaphragm in the embryological period. Although it is rarely seen in the adults, conditions such as intestinal volvulus, strangulation, or perforation with congenital diaphragm defect progress with high mortality and morbidity. In this study, we reported our case that we operated for intrathoracic gastric perforation with congenital diaphragmatic defect. When the patient admitted to the hospital, he had an atypical abdominal pain, significant back pain, and suspicious respiratory complaints. Radiological imaging showed that the stomach and the spleen were located in the left hemithorax due to diaphragmatic hernia also stomach was very dilated. Tachycardia, hypotension, and low saturation developed on the 2nd day of the patient's hospitalization. In the control imaging of the patient, in the left hemithorax, stomach was collapsed and the surrounding appearance compatible with hydropneumothorax, after that findings emergency laparotomy was decided. During the operation, as demonstrated by the radiological findings, a diaphragm defect was seen in the left posterolateral region of the diaphragm. The stomach and spleen were herniated to the left hemithorax from this defect. The stomach and spleen were reduced into the abdomen. The left hemithorax was lavaged with 2000 cc isotonic, left tube thoracostomy was applied, and the diaphragm was repaired. The anterior stomach was primarily repaired. In post-operative follow-up, there were no complications other than wound infection and thoracic tube of the patient was removed. The patient who tolerated enteral food was discharged from hospital with full recovery.

Label-Free Identification of Exosomes using Raman Spectroscopy and Machine Learning.

Exosomes, nano-sized extracellular vesicles (EVs) secreted from cells, carry various cargo molecules reflecting their cells of origin. As EV content, structure, and size are highly heterogeneous, their classification via cargo molecules by determining their origin is challenging. Here, a method is presented combining surface-enhanced Raman spectroscopy (SERS) with machine learning algorithms to employ the classification of EVs derived from five different cell lines to reveal their cellular origins. Using an artificial neural network algorithm, it is shown that the label-free Raman spectroscopy method's prediction ratio correlates with the ratio of HT-1080 exosomes in the mixture. This machine learning-assisted SERS method enables a new direction through label-free investigation of EV preparations by differentiating cancer cell-derived exosomes from those of healthy. This approach will potentially open up new avenues of research for early detection and monitoring of various diseases, including cancer.

Ionoacoustic application of an optical hydrophone to detect proton beam range in water.

BACKGROUND: Proton range uncertainty has been the main factor limiting the ability of proton therapy to concentrate doses to tumors to their full potential. Ionoacoustic (IA) range verification is an approach to reducing this uncertainty by detecting thermoacoustic waves emitted from an irradiated volume immediately following a pulsed proton beam delivery; however, the signal weakness has been an obstacle to its clinical application. To increase the signal-to-noise ratio (SNR) with the conventional piezoelectric hydrophone (PH), the detector-sensitive volume needs to be large, but it could narrow the range of available beam angles and disturb real-time images obtained during beam delivery. PURPOSE: To prevent this issue, we investigated a millimeter-sized optical hydrophone (OH) that exploits the laser interferometric principle. For two types of IA waves [γ-wave emitted from the Bragg peak (BP) and a spherical IA wave with resonant frequency (SPIRE) emitted from the gold fiducial marker (GM)], comparisons were made with PH in terms of waveforms, SNR, range detection accuracy, and signal intensity robustness against the small detector misalignment, particularly for SPIRE. METHODS: A 100-MeV proton beam with a 27 ns pulse width and 4 mm beam size was produced using a fixed-field alternating gradient accelerator and was irradiated to the water phantom. The GM was set on the beam's central axis. Acrylic plates of various thicknesses, up to 12 mm, were set in front of the phantoms to shift the proton range. OH was set distal and lateral to the beam, and the range was estimated using the time-of-flight method for γ-wave and by comparing with the calibration data (SPIRE intensity versus the distance between the GM and BP) derived from an IA wave transport simulation for SPIRE. The BP dose per pulse was 0.5-0.6 Gy. To measure the variation in SPIRE amplitude against the hydrophone misalignment, the hydrophone was shifted by ± 2 mm at a maximum in lateral directions. RESULTS: Despite its small size, OH could detect γ-wave with a higher SNR than the conventional PH (diameter, 29 mm), and a single measurement was sufficient to detect the beam range with a submillimeter accuracy in water. In the SPIRE measurement, OH was far more robust against the detector misalignment than the focused PH (FPH) used in our previous study [5%/mm (OH) versus 80%/mm (FPH)], and the correlation between the measured SPIRE intensity and the distance between the GM and BP agreed well with the simulation results. However, the OH sensitivity was lower than the FPH sensitivity, and about 5.6-Gy dose was required to decrease the intensity variation among measurements to less than 10%. CONCLUSION: The miniature OH was found to detect weak IA signals produced by proton beams with a BP dose used in hypofractionated regimens. The OH sensitivity improvement at the MHz regime is worth exploring as the next step.

The relationship of pre-operative vitamin D and TSH levels with papillary thyroid cancer.

OBJECTIVE: Our goal in this study is to analyze the correlation between papillary thyroid cancer (PTC) with elevated thyroid-stimulating hormone (TSH) levels and deficiency of vitamin D. METHODS: Patients who underwent thyroidectomy, also with available vitamin D test results preoperatively, were included in the study. The patients were separated into two different categories as having papillary thyroid carcinoma (Group 1), benign diseases (Group 2). According to the TSH (mUI/mL) level and vitamin D values, patients were categorized into four quarters. RESULTS: Preoperatively, TSH level (mean±SDmUI/mL) was higher in Group 1 (2.04±1.55) compared to Group 2 (1.82±1.94) significantly (p=0.029). Preoperatively, vitamin D levels (mean±SD) were higher in Group 1 (15.88±10.88) than in Group 2 (12.94±10.26) significantly (p=0.011). There was no significant difference between Group 1 and Group 2 according to the vitamin D deficiency (65.5%, 72.8%; respectively (p=0.472)). When categorized with reference to pre-operative vitamin D levels, the proportion of patients in Group 2 and Category 1 was higher significantly (p=0.031). CONCLUSION: Although the pre-operative TSH level was significantly higher in papillary thyroid carcinoma than benign thyroid diseases, the categorical distributions of the patients according to the TSH value were similar and the TSH values overlapped. Pre-operative mean vitamin D levels were similar in both PTC and benign thyroid disease groups so PTC was not associated with vitamin D deficiency.

The Role of Frozen Section Examination in Thyroid Surgery.

In endocrine pathology, frozen section (FS) examination is most commonly used for the intraoperative evaluation of thyroid and parathyroid tumors, as well as cervical lymph nodes. In the past, frozen section was considered a fundamental tool in thyroid surgery. However, with advancements in preoperative ultrasound and fine-needle aspiration biopsy (FNAB), there have been increasing queries about its routine use due to the improved preoperative diagnosis. Nowadays, while the use of FS during thyroidectomy has decreased, it is still used as an additional method for different purposes intraoperatively. FS may not always provide definitive results. If FS will alter the surgical plan or extent, it should be applied. Routine FS is not recommended for evaluating thyroid nodules. But in addition to FNAB, if FS results may change the operation plan or extent, they can be utilized. FS should not be applied for thyroid lesions smaller than 1 cm, and the entire lesion should not be frozen for FS. For the assessment of thyroid nodules, the use of FS is recommended based on the Bethesda categories of FNAB. In Bethesda I category nodules, FS may contribute to distinguishing between malignant and benign lesions and guide surgical treatment. In Bethesda II nodules, where the malignancy rate is low, the performance of FNAB and FS can be compared, but it's not recommended due to the lack of a significant contribution to the surgical strategy. The sensitivity of FS in Bethesda III and IV nodules is low; its contribution to the diagnosis is limited, and it does not provide an apparent benefit to treatment; therefore, it is not recommended. In Bethesda V nodules, FS can effectively confirm the malignancy diagnosis, contribute to the surgical strategy, and reduce the possibility of completion thyroidectomy, and accordingly, it is recommended for use. Nonetheless, in Bethesda V nodules with a benign FS report, the malignancy rate remains high, so it should not be used to rule out malignancy. In Bethesda VI nodules, the performance of FS is lower or comparable to FNAB and does not significantly contribute to the treatment strategy; hence, it is not recommended. Particularly in patients with papillary thyroid cancer, intraoperative FS can be effective in detecting extrathyroidal extension and can assist the surgeon in determining the extent of thyroid surgery and central neck dissection. FS has high sensitivity and specificity in evaluating the lymphatic status of the central region intraoperatively and can be used to determine the extent of central compartment node dissection. During thyroidectomy, FS examination can be used in recognizing parathyroid tissue and distinguishing it from fatty tissue, thymus, thyroid, lymph nodes, especially in differentiating metastatic lymph nodes.

Can Unilateral Therapeutic Central Lymph Node Dissection Be Performed in Papillary Thyroid Cancer with Lateral Neck Metastasis?

Objectives: Unilateral or bilateral prophylactic central neck dissection (CND) in papillary thyroid cancer (PTC) is still controversial. We aimed to evaluate the risk factors for contralateral paratracheal lymph node metastasis and whether CND might be performed unilaterally. Methods: Prospectively collected data of patients who underwent bilateral CND and lateral neck dissection (LND) with thyroidectomy due to PTC with lateral metastases, between January 2012 and November 2019, were evaluated retrospectively. The patients were divided into two groups according to the presence (Group 1) and absence (Group 2) of metastasis in the contralateral paratracheal region.A total of 42 patients (46 ±15.7 years) were operated. In the contralateral paratracheal region, Group 1 (35.7%) had metastases, while Group 2 (64.3%) had no metastases. In groups 1 and 2, metastasis rates were 100% vs 77.8% (p=0.073), 46.7% vs 18.5% (p=0.078), and 80% vs 40.7% (p=0.023) for the ipsilateralparatracheal, prelaryngeal and pretracheal lymph nodes, respectively.The number of metastatic lymph nodes in the central region was significantly higher in Group 1 compared to Group 2 as; 10.7±8.4 vs. 2.6±2.4 (p=0.001) in bilateral central region material; 8.3±7.4 vs. 2.9±2.7 (p=0.001) in lateral metastasis with ipsilateral unilateral central region; 3.8±3.4 vs. 1.9±1.9 (p=0.023) in ipsilateralparatracheal area; and 3.7±4.6 vs. 0.6±0.9 (p=0.001) in pretracheal region, respectively. However, no significant difference was found regarding the prelaryngeal region material (0.9±1.8 vs. 0.2±0.4 (p=0.71)). Results: >2 metastatic central lymph nodes in unilateral CND material (AUC: 0.814, p<0.001, J=0.563) can estimate contralateral paratracheal metastasis with 93% sensitivity, 63% specificity, while >2 pretracheal metastatic lymph nodes (AUC: 0.795, p<0.001, J: 0.563) can estimate contralateral paratracheal metastasis with 60% sensitivity and 96.3% specificity. Conclusion: In patients with lateral metastases, the rate of ipsilateralparatracheal metastasis is 85%, while the rate of contralateral paratracheal metastasis is 35.7%. The number of ipsilateral central region or pretracheal lymph node metastases may be helpful in predicting contralateral paratracheal lymph node metastases. Notably, unilateral CND may be performed in the presence of ≤ 2 metastases in the ipsilateral central region.

Contribution of intraoperative parathyroid hormone monitoring to the surgical success in minimal invasive parathyroidectomy.

Background: The contribution of intraoperative parathyroid hormone monitoring to minimally invasive parathyroidectomy remains controversial. We aimed to evaluate whether intraoperative parathyroid hormone monitoring monitoring could contribute to minimally invasive parathyroidectomy in these patients. Methods: The data of the patients whose preoperative ultrasonography and technetium-99 m sestamibi scintigraphy imagings were positive and concordant for one gland and who underwent minimally invasive parathyroidectomy between 2003 and 2018 in our clinic, were evaluated retrospectively. Blood samples were collected at pre-excisional period, and at post-excisional 10 and 20 min; the intaoperative parathyroid hormone was measured, and the surgery was terminated without waiting for the result. Patients were divided into 2 groups according to the postoperative results, as those with normocalcemia (Group 1) and those with persistence (Group 2). Results: There were 195 patients in Group 1 and 14 patients in Group 2. The cure rate at the first surgery was 93.3%. Cure was achieved after the second operation in all patients in Group 2. Recurrent disease developed in 1 patient in group 1 and the overall cure rate was 99.5%. If intraoperative parathyroid hormone had been evaluated, cure could have been achieved at the first surgery with additional exploration, in 10 (71.4%) of 14 patients according to the insufficient decrease in parathyroid hormone value at the 10 min in Group 2, and in 9 (64.3%) of 14 patients according to the parathyroid hormone value at 20 min. However, due to insufficient decrease (false negative) in the parathyroid hormone value at the 10 and 20 min the rate of false negatives and unnecessary exploration would be 9.5% and 2.5%, respectively. With additional exploration, the cure rate in the first surgery could be increased by 4.3%-97.6% according to the 20 min intraoperative parathyroid hormone value. Conclusion: The cure rate in minimally invasive parathyroidectomy can be increased by minimizing unnecessary conversion to bilateral neck exploration, by evaluating intraoperative parathyroid hormone at 10 min in patients with positive and concordant scans, and intraoperative parathyroid hormone at 20 min in patients with inadequate decrease at 10 min intraoperative parathyroid hormone.