Comparison of Surgical Outcomes of Transoral Versus Open Thyroidectomy for Graves Disease.

INTRODUCTION: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe alternative to thyroidectomy for thyroid goiter and provides the benefit of being scarless. However, the data on the use of TOETVA in patients with Graves disease are limited. This retrospective study compared the outcomes of Graves disease patients who underwent TOETVA versus those who underwent open thyroidectomy (OT). MATERIALS AND METHODS: Patients with Graves disease who received TOETVA or OT for bilateral total thyroidectomy between September 2017 and October 2022 were included. Patient demographics and surgical outcomes, including operation time, blood loss, length of stay, and complications, were compared. RESULTS: There were 15 patients in each group. The mean age in the TOETVA group was 35.80±8.13 years, which was significantly younger than that in the OT group, which was 51.53±14.22 years. Females predominated in both groups. The other demographic characteristics were similar in both groups. The operation time and intraoperative blood loss were also comparable. The postoperative stay and complications, including hypoparathyroidism, recurrent laryngeal nerve injury, surgical site infection, postoperative hemorrhage, and recurrence of hyperthyroidism, were not different between the 2 groups. There were 11 patients in the TOETVA group and 10 in the OT group who had thyroglobulin levels <0.1 ng/dL, indicating the completeness of total thyroidectomy in the 2 groups. There was no conversion of TOETVA to an open procedure. CONCLUSIONS: For carefully selected Graves patients, TOETVA offers a safe, scarless, and feasible alternative to conventional open thyroidectomy.

Transoral endoscopic and robotic thyroidectomy for thyroid cancer: the mid-term oncological outcome.

BACKGROUND: Traditional open thyroidectomy is the surgical standard for thyroid cancer; however, it inevitably leaves a visible scar on the neck and affects the patient's quality of life. Therefore, to avoid making a neck incision, the transoral endoscopic thyroidectomy vestibular approach (TOETVA) and transoral robotic thyroidectomy (TORT) have been developed recently, and the surgical outcomes of these techniques are as favorable as open surgery for benign disease. Additionally, positive short-term surgical outcomes have also been achieved in a few patients with thyroid cancer. However, no data on the mid-to-long-term recurrence and survival rates of transoral thyroidectomy in thyroid cancer are available. Therefore, in this study, we analyzed the surgical outcomes and mid-term oncological results of the TOETVA and TORT in patients with thyroid cancer. METHODS: We reviewed patients who had received TOETVA or TORT between July 2017 and November 2021 and followed up on their oncological outcomes until December 2022. Perioperative surgical and mid-term oncological outcomes were analyzed. RESULTS: The 115 patients underwent 122 operations (57 TOETVAs and 65 TORTs), including seven complete thyroidectomies for differentiated thyroid cancer (DTC), Stage I-II, including T1-T3, N0-N1a, and initial low- to high-risk groups. There was no conversion from transoral to open surgery. TORT required a longer operating time (median [interquartile range]) than TOETVA (lobectomy: 279 [250, 318] vs. 196 [173, 253] min, p < 0.001; bilateral total thyroidectomy: 375 [309, 433] vs. 279 [238, 312] min, p < 0.001); however, no difference was found between the two groups regarding perioperative complications. Complete thyroidectomy with a second transoral approach was safe. TOETVA and TORT achieved favorable oncological outcomes with 100% survival and 98.2% acceptable response (excellent and indeterminate response) during a mean 37.88 ± 12.42 months mid-term follow-up. CONCLUSIONS: Transoral endoscopic and robotic thyroidectomy was safe and achieved favorable mid-term oncological outcomes in a selected cohort of patients with early-stage DTC.

Artificial-Intelligence-Assisted Discovery of Genetic Factors for Precision Medicine of Antiplatelet Therapy in Diabetic Peripheral Artery Disease.

An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.

Developing a Prediction Model for 7-Year and 10-Year All-Cause Mortality Risk in Type 2 Diabetes Using a Hospital-Based Prospective Cohort Study.

Leveraging easily accessible data from hospitals to identify high-risk mortality rates for clinical diabetes care adjustment is a convenient method for the future of precision healthcare. We aimed to develop risk prediction models for all-cause mortality based on 7-year and 10-year follow-ups for type 2 diabetes. A total of Taiwanese subjects aged ≥18 with outpatient data were ascertained during 2007-2013 and followed up to the end of 2016 using a hospital-based prospective cohort. Both traditional model selection with stepwise approach and LASSO method were conducted for parsimonious models' selection and comparison. Multivariable Cox regression was performed for selected variables, and a time-dependent ROC curve with an integrated AUC and cumulative mortality by risk score levels was employed to evaluate the time-related predictive performance. The prediction model, which was composed of eight influential variables (age, sex, history of cancers, history of hypertension, antihyperlipidemic drug use, HbA1c level, creatinine level, and the LDL /HDL ratio), was the same for the 7-year and 10-year models. Harrell's C-statistic was 0.7955 and 0.7775, and the integrated AUCs were 0.8136 and 0.8045 for the 7-year and 10-year models, respectively. The predictive performance of the AUCs was consistent with time. Our study developed and validated all-cause mortality prediction models with 7-year and 10-year follow-ups that were composed of the same contributing factors, though the model with 10-year follow-up had slightly greater risk coefficients. Both prediction models were consistent with time.

Diagnostic pitfalls and therapeutic outcomes of the macrofollicular variant of papillary thyroid carcinoma.

BACKGROUND: The macrofollicular variant of papillary thyroid cancer (MFVPTC) is a rare histological variant of papillary thyroid cancer (PTC), with only 71 cases reported through 2014. This study analyzed the clinical, preoperative thyroid ultrasonography (US), and fine needle aspiration cytology (FNAC) features; and therapeutic outcomes of 11 patients with MFVPTC. METHODS: The records of 393 patients with histologically diagnosed follicular variant of papillary thyroid carcinoma (FVPTC), including 11 with MFVPTC, were retrospectively reviewed. Preoperative thyroid US findings, clinical presentation, treatment outcomes, and survival rates were analyzed. RESULT: Mean tumor size was significantly greater in patients with MFVPTC than that in those with FVPTC (4.2 ± 2.1 cm vs. 2.9 ± 1.7 cm; p = 0.016). No patient with MFVPTC had lymph node involvement, but one had a micrometastasis to the lung, which responded well to therapeutic radioiodine. All MFVPTC lesions were isoechoic on US. Eight nodules had calcifications and eight had irregular margins. FNAC showed that these tumors had low cellularity, absence or focal presence of enlarged clear nuclei, and subtle or focal nuclear features of PTC. Cells were, arranged in microfollicular pattern, with abundant colloid background. Multifocal PTCs were detected in the opposite lobe of two patients. All 11 patients with MFVPTC had excellent outcomes. No patient experienced recurrence, and survival rates were high. CONCLUSIONS: Malignant US criteria combined with FNAC features have a low preoperative diagnostic rate for MFVPTC. Surgery is recommended for patients with thyroid nodules larger than 4 cm and those with subtle and focal atypical nuclei in FNAC.

Differentiation of the Follicular Variant of Papillary Thyroid Carcinoma From Classic Papillary Thyroid Carcinoma: An Ultrasound Analysis and Complement to Fine-Needle Aspiration Cytology.

OBJECTIVES: It is difficult to establish a diagnosis of the follicular variant of papillary thyroid carcinoma (PTC) using fine-needle aspiration cytology (FNAC). Preoperative features on ultrasound (US) imaging are different between follicular PTC and classic PTC. This study developed a risk score system to differentiate follicular PTC from classic PTC and to correlate the risk score of follicular PTC with its FNAC categories and pathologic features. METHODS: The US features, FNAC results, and pathologic reports of 156 follicular PTC nodules and 152 classic PTC nodules from 296 patients with PTC along with their clinical characteristics were reviewed retrospectively. A risk score system based on US features was developed by multivariate logistic regression to differentiate classic PTC from follicular PTC nodules. The risk scores were then correlated with the FNAC category and pathologic features of the nodules. RESULTS: The US risk score (5 × echogenicity + 3 × calcifications + 3 × marginal regularity) had an area under the receiver operating characteristic curve of 0.85 and a cutoff value of 8.0, with specificity of 87% and sensitivity of 69% for predicting a classic PTC nodule. The follicular PTC nodules with low Bethesda categorization (I-III) had a median US risk score of 6 (range, 0-11), which was higher than that of nodules with high categorization (IV-VI; median, 3; range, 0-11). CONCLUSIONS: The US risk score may be useful in differentiating classic PTC from follicular PTC and complementary to FNAC in identifying follicular PTC.

Higher body weight and distant metastasis are associated with higher radiation exposure to the household environment from patients with thyroid cancer after radioactive iodine therapy.

There were insufficient data regarding radiation exposure to the household environment from patients with thyroid cancer who received radioactive iodine (RAI) therapy in Asia; we therefore performed the present study at the Chang Gung Memorial Hospital in Keelung, Taiwan.Patients with papillary or follicular thyroid cancer who received 3.7 GBq (100 mCi) RAI were enrolled in this prospective hospital-based study. The enrolled patients were asked to place a thermoluminescent dosimeter in the living room, bedroom, and bathroom of their houses for 4 weeks to measure radiation exposure to the household environment.A total of 43 patients (18 men and 25 women; mean age 51 ±â€Š13 years) who received 3.7 GBq (100 mCi) RAI completed the study. The mean value of total radiation exposure over 4 weeks from the patients to the bedroom, bathroom, and living room (eliminating the background radiation factor) was 0.446 ±â€Š0.304 (0.088-1.382) mSv. We divided the patients into 2 groups: those with more than and less than the mean value of total radiation exposure to the bedroom, bathroom, and living room. Factors associated with the higher amount of radiation exposure from the patients to the household environment were patient body weight (P = .025, univariate analysis; P = .037, multivariate analysis, odds ratio [95% confidence interval] 1.067 [1.004-1.134]) and distant metastases based on I post-therapy scanning (P = .041, univariate analysis; P = .058, multivariate analysis, odds ratio [95% confidence interval] 6.453 [0.938-44.369]); age, sex, body mass index, renal function, serum stimulated thyroglobulin level, and recombinant human thyroid-stimulating hormone use were not associated with the amount of radiation exposure from the patients to the household environment.Higher body weight and distant metastases may be the best predictors for higher radiation exposure to the household environment from patients with thyroid cancer after RAI therapy.

Therapeutic Outcomes of Patients with Multifocal Papillary Thyroid Microcarcinomas and Larger Tumors.

A retrospective review of 626 patients with multifocal papillary thyroid carcinoma (PTC) including 147 patients (23.5%) with multifocal papillary thyroid microcarcinoma (PTMC) from a total of 2,536 patients with PTC who visited the Chang Gung Medical Center in Linkou, Taiwan, was performed. A comparison of the clinical features between 626 multifocal and 1,910 solitary PTC cases showed that patients in the multifocal PTC group were older and had a smaller mean tumor size, a more advanced tumor-node-metastasis (TNM) stage, and a higher percentage of nonremission status compared to patients in the solitary PTC group. Of the 626 patients with multifocal PTC, the group with larger tumors showed a more advanced TNM stage, a higher percentage of lymph node metastasis and soft tissue invasion, and a higher nonremission rate compared to the multifocal PTMC group. Of the 626 patients with multifocal PTC, 25 patients (4%) died during a mean follow-up period of 7.1 ± 5.3 years. Kaplan-Meier survival curves showed a significantly lower survival rate associated with multifocal PTMC compared to that with solitary PTMC.

Modified endoscopic submucosal dissection with enucleation for treatment of gastric subepithelial tumors originating from the muscularis propria layer.

BACKGROUND: Gastric subepithelial tumors are usually asymptomatic and observed incidentally during endoscopic examination. Although most of these tumors are considered benign, some have a potential for malignant transformation, particularly those originating from the muscularis propria layer. For this type of tumor, surgical resection is the standard treatment of choice. With recent advent of endoscopic resection techniques and devices, endoscopic submucosal dissection (ESD) has been considered as an alternative way of treatment. The aim of this study is to demonstrate the feasibility of a modified ESD technique with enucleation for removal of gastric subepithelial tumors originating from the muscularis propria layer, and to evaluate its efficacy and safety. METHODS: From November 2009 to May 2011, a total of 16 patients received a modified ESD with enucleation for their subepithelial tumors. All tumors were smaller than 5 cm and originated from the muscularis propria layer of the stomach, as shown by endoscopic ultrasonography (EUS). The procedure was conducted with an insulated-tip knife 2. Patient's demographics, tumor size and pathological diagnosis, procedure time, procedure-related complication, and treatment outcome were reviewed. RESULTS: Fifteen of the sixteen tumors were successful complete resection. The mean tumor size measured by EUS was 26.1 mm (range: 20-42 mm). The mean procedure time was 52 minutes (range: 30-120 minutes). Endoscopic features of the 4 tumors were pedunculated and 12 were sessile. Their immunohistochemical diagnosis was c-kit (+) stromal tumor in 14 patients and leiomyoma in 2 patients. There was no procedure-related perforation or overt bleeding. During a mean follow up duration of 14.8 months (range: 6-22 months), there was no tumor recurrence or metastasis. CONCLUSIONS: Using a modified ESD with enucleation for treatment of gastric subepithelial tumors originating from the muscularis propria layer and larger than 2 cm, complete resection can be successfully performed without serious complication. It is a safe and effective alternative to surgical therapy for these tumors of 2 to 5 cm in size.

Axial length and proliferative diabetic retinopathy.

PURPOSE: To determine the correlation between axial length and diabetic retinopathy (DR) in patients with diabetes mellitus for 10 years or more. METHODS: This study was a prospective, observational, cross-sectional study. Patients with diabetes for 10 years or more were included. We excluded eyes with any other significant ocular disease or any prior intraocular surgery, except uncomplicated cataract surgery. Only one eye of each patient was included as the study eye. The severity of DR was graded as no DR, non-proliferative DR (NPDR), or proliferative DR (PDR). Axial length was measured by A-scan ultrasound (10 MHz Transducer, AL-2000 Biometer/Pachymeter; Tomey, Phoenix, AZ). Univariate logistic regression models were used to evaluate the relationship between the dependent variables (any DR, PDR) and all potential risk factors. Axial length and other factors with p value <0.1 were included in multivariate logistic regression models. Backward selection based on the likelihood ratio statistic was used to select the final models. RESULTS: We included 166 eyes from 166 patients (93 female and 73 male; mean age, 68.8 years). The mean diabetes duration was 15.4 years. Fifty-four (32.5%) eyes had no DR, 72 (43.4%) eyes had NPDR, and 40 (24.1%) eyes had PDR. In univariate analysis, hypertension (p = 0.009), renal impairment (p = 0.079), and insulin use (p = 0.009) were associated with developing any DR. Hypertension (p = 0.042), renal impairment (p = 0.014), insulin use (p = 0.040), pseudophakia (p = 0.019), and axial length (p = 0.076) were associated with developing PDR. In multivariate analysis, hypertension (p = 0.005) and insulin use (p = 0.010) were associated with developing any DR. Hypertension (p = 0.020), renal impairment (p = 0.025), pseudophakia (p = 0.006), and axial length (p = 0.024) were associated with developing PDR. CONCLUSIONS: This observational study suggests an inverse relationship between axial length and the development of PDR in patients with diabetes for 10 years or more. No relationship was found between axial length and the development of any DR.

Obtained mydriasis in long-term type 2 diabetic patients.

PURPOSE: The purpose of this study was to evaluate obtained mydriasis and prevalence of small pupil in long-term type 2 diabetic patients. METHODS: A prospective observational cross-sectional study was carried out. We included 107 eyes from 107 patients (mean age: 60.8) with long-term (≥10 years) type 2 diabetes mellitus. Patients were divided into 2 groups: no apparent diabetic retinopathy (group 1, n=33) and diabetic retinopathy (group 2, n=74). Exclusion criteria were eyes with prior intraocular surgeries, presence of other ocular disorders that may affect iris, or any other condition that precludes the precise measurement of pupil size. Sixty eyes in 60 age-matched nondiabetic patients (mean age: 61.0) scheduled for routine fundoscopy exam were enrolled as control. We measured pupil diameter by pupil gauges at 40 min after instillation of eye drops (phenylephrine 10% and tropicamide 1%). Small pupil was defined as pupil diameter of 6 mm or less. RESULTS: Mean pupil diameter was 8.07 mm [standard deviation (SD): 0.59 mm] in the control group, 7.46 mm (SD: 0.71 mm) in group 1, and 7.24 mm (SD: 0.83 mm) in group 2. Both group 1 (P<0.001) and group 2 (P<0.001) showed significant difference when compared with the control group. The incidences of small pupil were 1.9% in the control group, 6.1% in group 1, and 13.5% in group 2. When compared with control, group 2 showed significantly higher incidence of small pupil (P=0.023). CONCLUSIONS: Long-term diabetic patients showed poorer response to pharmacological mydriasis than nondiabetic patients. Higher prevalence of small pupil size was found in patients with diabetic retinopathy.

Achalasia combined with esophageal intramural hematoma: case report and literature review.

A 62-year-old male patient was admitted to our hospital due to severe chest pain, odynophagia, and hematemesis. Chest computed tomography showed an esophageal submucosal tumor. Esophagogastroduodenoscopy (EGD) revealed a longitudinal purplish bulging tumor of the esophagus. Endoscopic ultrasound (EUS) showed a mixed echoic tumor with partial liquefaction from the submucosal layer. The patient was diagnosed with esophageal intramural hematoma as well as achalasia by upper gastrointestinal endoscopy, esophagography and esophageal manometry. The patient was managed conservatively with intravenous nutrition, and oral feeding was discontinued. Follow-up EGD and EUS showed complete recovery of the esophageal wall, and finally, the patient underwent endoscopic dilatation for achalasia. The patient was symptom free at the time when we wrote this manuscript.

Endoscopic ultrasound-guided tru-cut biopsy for diagnosis of gastrointestinal stromal tumors.

BACKGROUND/AIMS: The most common mesenchymal tumors of gastrointestinal tract are gastrointestinal stromal tumors (GIST). These tumors originate from muscularis propria layer. Tissue diagnosis is usually difficult by endoscopic mucosal biopsy. The aim of this study is to evaluate the utility of endoscopic ultrasound-guided Tru-Cut biopsy (EUS-TCB) for GISTs before treatment. METHODOLOGY: A total of six patients in the period between June 2006 and May 2009 were included in this study. EUS-TCB was performed with a 19-gauge core needle to obtain sufficient specimen for pathological and immunohistochemical studies. All tumor sizes were larger than 2 cm. Specimen size and the number of needle passes were both recorded. RESULTS: Core tissues were successfully procured by EUS-TCB in all tumors (100%). The mean tumor size was 50 mm (range 30-75 mm). The final pathological diagnosis was c-kit positive stromal tumor in five patients and leiomyoma in one patient. The mean size of specimen was 8 mm (range 3-13 mm) and the mean number of needle passes was 2 (range 1-3). No patient developed complications after the procedure. CONCLUSION: EUS-TCB is a safe, quicker procedure that offers sufficient tissue acquisition for pathological diagnosis and clinical decision-making in patients with GISTs.