Unraveling the impact of cancer-associated fibroblasts on hypovascular pancreatic neuroendocrine tumors.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) with low microvessel density and fibrosis often exhibit clinical aggressiveness. Given the contribution of cancer-associated fibroblasts (CAFs) to the hypovascular fibrotic stroma in pancreatic ductal adenocarcinoma, investigating whether CAFs play a similar role in PNETs becomes imperative. In this study, we investigated the involvement of CAFs in PNETs and their effects on clinical outcomes. METHODS: We examined 79 clinical PNET specimens to evaluate the number and spatial distribution of α-smooth muscle actin (SMA)-positive cells, which are indicative of CAFs. Then, the findings were correlated with clinical outcomes. In vitro and in vivo experiments were conducted to assess the effects of CAFs (isolated from clinical specimens) on PNET metastasis and growth. Additionally, the role of the stromal-cell-derived factor 1 (SDF1)-AGR2 axis in mediating communication between CAFs and PNET cells was investigated. RESULTS: αSMA-positive and platelet-derived growth factor-α-positive CAFs were detected in the hypovascular stroma of PNET specimens. A higher abundance of α-SMA-positive CAFs within the PNET stroma was significantly associated with a higher level of clinical aggressiveness. Notably, conditioned medium from PNET cells induced an inflammatory phenotype in isolated CAFs. These CAFs promoted PNET growth and metastasis. Mechanistically, PNET cells secreted interleukin-1, which induced the secretion of SDF1 from CAFs. This cascade subsequently elevated AGR2 expression in PNETs, thereby promoting tumor growth and metastasis. The downregulation of AGR2 in PNET cells effectively suppressed the CAF-mediated promotion of PNET growth and metastasis. CONCLUSION: CAFs drive the growth and metastasis of aggressive PNETs. The CXCR4-SDF1 axis may be a target for antistromal therapy in the treatment of PNET. This study clarifies mechanisms underlying PNET aggressiveness and may guide future therapeutic interventions targeting the tumor microenvironment.

Imaging Characteristics and Interpretation Strategy for Renal Hyperparathyroidism: A Retrospective 4-Dimensional Computed Tomography Study.

OBJECTIVE: Parathyroidectomy treats uncontrolled renal hyperparathyroidism (RHPT), requiring identification of all glands. Three types of enhancement are proposed. Type A lesions have higher arterial phase attenuation than the thyroid, type B lesions lack higher arterial phase attenuation but have lower venous phase attenuation, and type C lesions have neither higher arterial phase attenuation nor lower venous phase attenuation than the thyroid. We aimed to outline the image features of problematic parathyroid glands in RHPT and propose a 4-dimensional computed tomography (4DCT) interpretation algorithm. METHODS: This retrospective study involved data collection from patients with RHPT who underwent preoperative 4DCT for parathyroidectomy between January and November 2022. Pathologically confirmed parathyroid lesions were retrospectively identified on 4DCT according to the location and size described in the surgical notes. The attenuation of parathyroid lesions and the thyroid glands was assessed in 3 phases, and demographic data of the patients were collected. RESULTS: Ninety-seven pathology-proven parathyroid glands from 27 patients were obtained, with 86 retrospectively detected on 4DCT. In the arterial phase, the attenuation of parathyroid lesions in RHPT did not exceed that of the thyroid gland (P < .001). In the venous phase, parathyroid lesions demonstrated lower attenuation than the thyroid gland (P < .001). A total of 81 parathyroid lesions (94.2%) exhibited type B patterns. CONCLUSION: Unlike primary hyperparathyroidism, lesions in RHPT exhibited more type B enhancement, making them less readily identifiable in the arterial phase. Therefore, we propose a distinct imaging interpretation strategy to locate these problematic glands more efficiently.

Can Kidney Organoid Xenografts Accelerate Therapeutic Development for Genetic Kidney Disorders?

A number of genetic kidney diseases can now be replicated experimentally, using kidney organoids generated from human pluripotent stem cells. This methodology holds great potential for drug discovery. Under in vitro conditions, however, kidney organoids remain developmentally immature, develop scarce vasculature, and may contain undesired off-target cell types. Those critical deficiencies limit their potential as disease-modeling tools. Orthotopic transplantation under the kidney capsule improves the anatomic maturity and vascularization of kidney organoids, while reducing off-target cell content. The improvements can translate into more accurate representations of disease phenotypes and mechanisms in vivo . Recent studies using kidney organoid xenografts highlighted the unique potential of this novel methodology for elucidating molecular mechanisms driving monogenic kidney disorders and for the development ofnovel pharmacotherapies.

Immunocyte profiling changes in patients received epidural versus intravenous analgesia after pancreatectomy: A randomized controlled trial.

BACKGROUND: Perioperative immunosuppressants, such as surgical stress and opioid use may downregulate anti-cancer immunocytes for patients undergoing pancreatectomy. Thoracic epidural analgesia (TEA) may attenuate these negative effects and provide better anti-cancer immunocyte profile change than intravenous analgesia using opioid. METHODS: We randomly assigned 108 adult patients undergoing pancreatectomy to receive one of two 72-h postoperative analgesia protocols: one was TEA, and the other was intravenous patient-controlled analgesia (IV-PCA). The perioperative proportional changes of immunocytes relevant to anticancer immunity-namely natural killer (NK) cells, cytotoxic T cells, helper T cells, mature dendritic cells, and regulatory T (Treg) cells were determined at 1 day before surgery, at the end of surgery and on postoperative day 1,4 and 7 using flow cytometry. In addition, the progression-free survival and overall survival between the two groups were compared. RESULTS: After surgery, the proportions of NK cells and cytotoxic T cells were significantly decreased; the proportion of B cells and mature dendritic cells and Treg cells were significantly increased. However, the proportions of helper T cells exhibited no significant change. These results were comparable between the two groups. Furthermore, there were no significant differences in progression-free survival (52.75 [39.96] and 57.48 [43.66] months for patients in the TEA and IV-PCA groups, respectively; p = 0.5600) and overall survival (62.71 [35.48] and 75.11 [33.10] months for patients in the TEA and IV-PCA groups, respectively; p = 0.0644). CONCLUSIONS: TEA was neither associated with favorable anticancer immunity nor favorable oncological outcomes for patients undergoing pancreatectomy.

Novel Non-duct-to-Mucosa Pancreaticojejunostomy Reconstruction After Pancreaticoduodenectomy: Focus on the Occurrence of Post-pancreatectomy Hemorrhage and Intra-abdominal Abscess.

BACKGROUND: Postoperative pancreatic fistulas (POPFs) are considered inevitable in some patients after pancreaticoduodenectomy (PD), and measures to minimize their clinical impact are needed. Postpancreatectomy hemorrhage (PPH) and intra-abdominal abscess (IAA) are the most severe POPF-related complications, and concomitant leakage of contaminated intestinal content is considered the main cause. An innovative method, modified non-duct-to-mucosa pancreaticojejunostomy (TPJ), was created to prevent concomitant leakage of intestinal content, and its effectiveness was compared between two periods. METHODS: All PD patients undergoing pancreaticojejunostomy from 2012 to 2021 were included. The TPJ group consisted of 529 patients recruited from January 2018 to December 2021. A total of 535 patients receiving the conventional method (CPJ) from January 2012 to June 2017 were used as a control group. PPH and POPF were defined according to the International Study Group of Pancreatic Surgery definition, but only PPH grade C was included for analysis. An IAA was defined as a collection of postoperative fluid managed by CT-guided drainage with documental culture. RESULTS: There were no significant differences in the rate of POPF between the two groups (46.0% vs. 44.8%; p = 0.700). Furthermore, the percentages of bile in the drainage fluid in the TPJ and CPJ groups were 2.3% and 9.2%, respectively (p < 0.001). Lower proportions of PPH (0.9% vs. 6.5%; p < 0.001) and IAA (5.7% vs. 10.8%; p < 0.001) were observed for TPJ than for CPJ. On adjusted models, TPJ was significantly associated with a lower rate of PPH (odds ratio [OR] 0.132, 95% confidence interval [CI] 0.051-0.343; p < 0.001) and IAA (OR 0.514, 95% CI 0.349-0.758; p = 0.001) than CPJ. CONCLUSIONS: TPJ is feasible to be performed and is associated with a similar rate of POPF but a lower percentage of concomitant bile in the drainage fluid and subsequent rates of PPH and IAA than CPJ.

Pancreatic neck transection using a harmonic scalpel increases risk of biochemical leak but not postoperative pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: The effect of a harmonic scalpel on postoperative pancreatic fistula (POPF) has not been addressed. This study assessed the effect of pancreatic neck transection using a harmonic scalpel on rate and severity of POPF after pancreaticoduodenectomy (PD). METHODS: This retrospective analysis included patients who underwent PD at National Taiwan University Hospital between July 2015 and March 2019. We compared rate and severity of POPF between patients who underwent pancreatic neck transection using a harmonic scalpel versus electrosurgical unit. RESULTS: Of 422 consecutive PDs, the pancreatic neck was transected using a harmonic scalpel or electrosurgical unit in 144 and 278 patients, respectively. Use of a harmonic scalpel significantly increased risk of biochemical leak (25.7% versus [vs] 10.8%; P < 0.05) but not clinically relevant POPF (CR-POPF; 30.2% vs 26.4%; P = 0.41). Harmonic transection was an independent predictor of biochemical leak (odds ratio [OR] = 2.93; P < 0.05) but not CR-POPF (OR = 0.83; P = 0.41) or other major complications (OR = 0.72; P = 0.27). There was no significant intergroup difference in postoperative hospital stay. CONCLUSION: Pancreatic neck transection using a harmonic scalpel increased risk of biochemical leak but not CR-POPF or other major complications.

The effect of performing two pancreatoduodenectomies by a single surgical team in one day on surgeons and patient outcomes.

BACKGROUND: The centralization of pancreatoduodenectomy (PD) has been shown to improve patient outcomes. The scheduling of two PDs in one day is one option to shorten the waiting time for patients referred to high volume centers. The effect on the surgical team or patient outcomes of such an approach have not previously been explored. This study aimed to investigate the effect of scheduling two PDs in one day on the surgeon's workload and patient outcomes. METHODS: A retrospective review of patients undergoing PD by a single surgeon between 2007 and 2018 was performed. Patients were allocated into: first PD (FIRSTPD group) or second PD (SECONDPD group) according to the position on the surgical operating list. The intraoperative, postoperative outcomes, and workload (the Surgery Task Load Index; SURG-TLX) were assessed between two groups. RESULTS: A total of 967 (91%) and 101 (9%) patients were included in the FIRSTPD and SECONDPD group, respectively. There were no differences in the duration of surgery (coefficient = -9.65; 95% confidence interval: -29.26 to 9.94; P = 0.334), incidence of major complications (odds ratio = 1.08; 95% confidence interval: 0.67-1.73; P = 0.739), or 90-day mortality (odds ratio = 1.03; 95% confidence interval: 0.12-8.53; P = 0.978) for those patients in the SECONDPD group as compared to the FIRSTPD group. The mean scores of two (physical and temporal demand) of the six SURG-TLX subscales of surgical workload were recorded as significantly higher by surgeons following two PD's as compared to one PD. CONCLUSIONS: Although scheduling a second PD in one day shows no association with adverse patient outcomes, there is an increase in the physical and temporal subscales of surgical workload and consideration should be given to how this could be minimized.

Endoscopic Retrograde Biliary Drainage Causes Intra-Abdominal Abscess in Pancreaticoduodenectomy Patients: An Important But Neglected Risk Factor.

BACKGROUND: Patients with periampullary cancer frequently suffer obstructive jaundice and commonly require preoperative biliary drainage (PBD) for relief and to avoid related complications. Although research has established a correlation between PBD and surgical wound infection, the impact of PBD on major infectious complications (intra-abdominal abscess [IAA]) and overall mortality remains debatable. We hypothesized that PBD could lead to IAA and mortality, and evaluated their correlation in patients undergoing pancreaticoduodenectomy (PD). METHODS: We enrolled patients undergoing PD at an Asian academic medical center between 2007 and 2016. The types of PBD included endoscopic retrograde biliary drainage (ERBD) and percutaneous transhepatic cholangiography and drainage (PTCD). The primary outcome was IAA, defined as the presence of pus or infected fluid inside the abdominal cavity and with documented infectious pathogens. RESULTS: There was one (0.1%) 30-day mortality and eight (0.9%) 90-day mortalities among 899 consecutive patients examined. More than one-quarter of patients had PBD (n = 237, 26.4%; 165 ERBD, 72 PTCD). In the ERBD, PTCD, and non-PBD groups, the IAA rates were 37.0%, 16.7%, and 10.6%, respectively. On multivariate analysis, ERBD (odds ratio 3.67; 95% confidence interval 2.22-6.06; p < 0.001) was the only significant factor associated with IAA. No significant factor was found to analyze variables associated with mortality. CONCLUSIONS: ERBD, but not PTCD, is associated with an increased risk of IAA in patients undergoing PD, which suggests that ERBD should be avoided whenever possible to prevent IAA. Further randomized clinical trials should be conducted to validate this relationship.

Prospective comparison of (4S)-4-(3-18F-fluoropropyl)-L-glutamate versus 18F-fluorodeoxyglucose PET/CT for detecting metastases from pancreatic ductal adenocarcinoma: a proof-of-concept study.

PURPOSE: (4S)-4-(3-18F-Fluoropropyl)-L-glutamate (FSPG) positron emission tomography (PET) reflects system xC- transporter (xCT) expression. FSPG PET has been used to detect brain, lung, breast and liver cancer with only modest success. There is no report on the use of FSPG PET in pancreatic ductal adenocarcinoma (PDAC), presumably because of normal xCT expression in the pancreas. Nonetheless, the tissue-specific expression of xCT in the pancreas suggests that FSPG PET may be ideal for identifying metastasized PDAC. METHODS: The performance of FSPG in detecting PDAC metastases was compared with that of 18F-fluorodeoxyglucose (FDG) in small-animal PET studies in seven PDAC tumour-bearing mice and in prospective PET/computed tomography (CT) studies in 23 patients with tissue-confirmed PDAC of stage III or stage IV. All PET/CT results were correlated with the results of histopathology or contrast-enhanced CT (ceCT) performed 3 and 6 months later. RESULTS: In the rodent model, FSPG PET consistently found more PDAC metastases earlier than FDG PET. FSPG PET showed a trend for a higher sensitivity, specificity and diagnostic accuracy than FDG PET in detecting PDAC metastases in a patient-based analysis: 95.0%, 100.0% and 95.7%, and 90.0%, 66.7% and 90.0%, respectively. In a lesion-based analysis, FSPG PET identified significantly more PDAC metastases, especially in the liver, than FDG PET (109 vs. 95; P = 0.0001, 95% CI 4.9-14.6). The tumour-to-background ratios for FSPG and FDG uptake on positive scans were similar (FSPG 4.2 ± 4.3, FDG 3.6 ± 3.0; P = 0.44, 95% CI -1.11 to 0.48), despite a lower tumour maximum standardized uptake value in FSPG-avid lesions (FSPG 4.2 + 2.3, FDG 7.7 + 5.7; P = 0.002, 95% CI 0.70-4.10). Because of the lower physiological activity of FSPG in the liver, FSPG PET images of the liver are more easy to interpret than FDG PET images, and therefore the use of FSPG improves the detection of liver metastasis. CONCLUSION: FSPG PET is superior to FDG PET in detecting metastasized PDAC, especially in the liver.

Multiparametric PET/MR imaging biomarkers are associated with overall survival in patients with pancreatic cancer.

PURPOSE: To correlate the overall survival (OS) with the imaging biomarkers of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy, and glucose metabolic activity derived from integrated fluorine 18 fluorodeoxyglucose positron emission tomography (18F-FDG PET)/MRI in patients with pancreatic cancer. METHODS: This prospective study was approved by the institutional review board and informed consent was obtained from all participants. Sixty-three consecutive patients (mean age, 62.7 ± 12 y; men/women, 40/23) with pancreatic cancer underwent PET/MRI before treatment. The imaging biomarkers were comprised of DCE-MRI parameters (peak, IAUC 60 , K trans , k ep , v e ), the minimum apparent diffusion coefficient (ADCmin), choline level, standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) of the tumors. The relationships between these imaging biomarkers with OS were evaluated with the Kaplan-Meier and Cox proportional hazard models. RESULTS: Seventeen (27%) patients received curative surgery, with the median follow-up duration being 638 days. Univariate analysis showed that patients at a low TNM stage (≦3, P = 0.041), high peak (P = 0.006), high ADCmin (P = 0.002) and low TLG (P = 0.01) had better OS. Moreover, high TLG/peak ratio was associated with poor OS (P = 0.016). Multivariate analysis indicated that ADCmin (P = 0.011) and TLG/peak ratio (P = 0.006) were independent predictors of OS after adjustment for age, gender, tumor size, and TNM stage. The TLG/peak ratio was an independent predictor of OS in a subgroup of patients who did not receive curative surgery (P = 0.013). CONCLUSION: The flow-metabolism mismatch reflected by the TLG/peak ratio may better predict OS than other imaging biomarkers from PET/MRI in pancreatic cancer patients.

Life history traits and exploitation affect the spatial mean-variance relationship in fish abundance.

Fishing is expected to alter the spatial heterogeneity of fishes. As an effective index to quantify spatial heterogeneity, the exponent b in Taylor's power law (V = aMb) measures how spatial variance (V) varies with changes in mean abundance (M) of a population, with larger b indicating higher spatial aggregation potential (i.e., more heterogeneity). Theory predicts b is related with life history traits, but empirical evidence is lacking. Using 50-yr spatiotemporal data from the California Current Ecosystem, we examined fishing and life history effects on Taylor's exponent by comparing spatial distributions of exploited and unexploited fishes living in the same environment. We found that unexploited species with smaller size and generation time exhibit larger b, supporting theoretical prediction. In contrast, this relationship in exploited species is much weaker, as the exponents of large exploited species were higher than unexploited species with similar traits. Our results suggest that fishing may increase spatial aggregation potential of a species, likely through degrading their size/age structure. Results of moving-window cross-correlation analyses on b vs. age structure indices (mean age and age evenness) for some exploited species corroborate our findings. Furthermore, through linking our findings to other fundamental ecological patterns (occupancy-abundance and size-abundance relationships), we provide theoretical arguments for the usefulness of monitoring the exponent b for management purposes. We propose that age/size-truncated species might have lower recovery rate in spatial occupancy, and the spatial variance-mass relationship of a species might be non-linear. Our findings provide theoretical basis explaining why fishery management strategy should be concerned with changes to the age and spatial structure of exploited fishes.

PET/MRI in pancreatic and periampullary cancer: correlating diffusion-weighted imaging, MR spectroscopy and glucose metabolic activity with clinical stage and prognosis.

PURPOSE: To correlate the clinical stage and prognosis of pancreatic or periampullary cancer with the imaging biomarkers on diffusion-weighted imaging, magnetic resonance spectroscopy and glucose metabolic activity derived from integrated PET/MRI. METHODS: This prospective study was approved by the institutional review board and informed consent was obtained. The study group comprised 60 consecutive patients with pancreatic or periampullary cancer who underwent PET/MRI before treatment. The imaging biomarkers were the minimal apparent diffusion coefficient (ADCmin), choline levels, standardized uptake values, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of the tumours. The relationships between these biomarkers and clinical TNM stage were evaluated using the Pearson test and the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUROC) was used to evaluate accuracy. The correlation between the imaging biomarker and progression-free survival (PFS) was investigated using the Cox proportional hazards model. RESULTS: ADCmin was significantly lower in N1 and TNM stage 3+ tumours. Choline levels significantly higher in T4 tumours. TLG was significantly higher in T4, N1 and TNM stage 3+ tumours. MTV was significantly higher in T4, N1, M1, and TNM stage 3+ tumours (all P < 0.05). The MTV/ADCmin ratio exhibited the highest AUROC for predicting T4, N1, M1, and advanced TNM stages tumours, and was an independent predictor of PFS (P = 0.018) after adjustment for age, sex, tumour size and stage. CONCLUSION: The imaging biomarkers from integrated PET/MRI may predict clinical stage and PFS in patients with pancreatic or periampullary cancer.

Distal Enteral Feeding Helps Blood Sugar Control in Pancreatectomized Patients.

BACKGROUND: The change in the route of food passage after pancreaticoduodenectomy (PD) is quite similar to the change after gastric bypass surgery; both procedures bypass the duodenum and directly connect to the distal jejunum. Moreover, both procedures result in resolution of type 2 diabetes mellitus. Therefore, more distal enteral anastomosis after PD may further improve glycemic status. METHODS: To test the effect of distal enteral feeding on glucose metabolism in patients after PD, we performed a meal test on 20 patients via a nasogastric tube [proximal feeding group (PFG)] on post-operative day 5 and then via an intra-operatively placed jejunostomy feeding tube [distal feeding group (DFG)] on post-operative day. Blood samples were assessed for hormones and glucose. RESULTS: The AUC0-120 min levels of GLP-1, C-peptide, and insulin after distal feeding were significantly higher than after proximal feeding. The AUC0-120 min levels of glucose in the DFG were significantly lower than in the PFG. CONCLUSIONS: More distal enteral feeding contributed to better glucose metabolism after PD.

Obstructive jaundice as a complication of a right hepatic artery pseudoaneurysm after laparoscopic cholecystectomy.

A hepatic artery pseudoaneurysm is a rare, but a potentially life-threatening complication after laparoscopic cholecystectomy (LC). Obstructive jaundice owing to a hepatic artery pseudoaneurysm after LC has never been reported. We report a patient with a hepatic artery pseudoaneurysm after LC who presented with tarry stools, bloody drainage and obstructive jaundice.

Placement of Nasogastric Tubes in Pancreaticoduodenectomy Patients: Switching from Immediate Intraoperative Removal to Avoiding Unnecessary Perioperative Use.

BACKGROUND: The placement of nasogastric tubes (NGTs) in abdominal surgery has been adopted for decades to attenuate ileus and prevent aspiration pneumonia. In the recent era, the guidelines recommend not using NGT routinely, and even in pancreaticoduodenectomy (PD), immediate removal of NGT in operating rooms (ORs) was suggested. However, the clinical outcome and safety of abandoning NGT during the pre-PD and intra-PD periods remain unknown. METHODS: We conducted a single-center retrospective review on adult PD patients aged between 20 and 75 years from 2013 to 2022. The study population was grouped into the NGT group (NGT was placed before PD and immediately removed in the ORs) and the non-NGT group (NGT was not placed preoperatively). Safety was evaluated by the number of adverse events. The primary aim of this study is to evaluate the need of NGT insertion in ORs among PD patients. RESULTS: The case numbers in the NGT and non-NGT groups were 391 and 578, respectively. No case in the non-NGT group needed the intraoperative insertion of NGT. The rate of pulmonary complications was 2.3% in the NGT group compared to 1.6% in the non-NGT group (P = 0.400). Furthermore, there were no significant differences in terms of rates of major complications (12.8% vs. 9.3%, P = 0.089) or mortality (1.0% vs. 1.0%, P =0.980) between the two groups. The rates of the postoperative insertion of NGT in the NGT and non-NGT groups were 2.6% and 2.8% (P = 0.840), respectively. CONCLUSION: For selected PD patients, the placement of NGT during pre-PD and intra-PD periods may be safely omitted. This primary study is considered the first foundation stone in the extension of the element of no NGT in PD.

Comparison of safety, efficacy, and patient satisfaction with thermal ablation versus endoscopic thyroidectomy for benign thyroid nodules in a propensity-matched cohort.

BACKGROUND: Thyroid nodules (TNs) often require intervention due to symptomatic or cosmetic concerns. Radiofrequency ablation (RFA) has shown promise as a treatment option, offering potential advantages without neck scars. Recently, the scarless treatment alternative of transoral endoscopic thyroidectomy vestibular approach (TOETVA) has emerged. When surgery can be performed in a scarless manner, it remains unclear whether ablation is still the preferred treatment choice. This study aims to compare the safety, efficacy, and patient satisfaction of RFA and TOETVA. STUDY DESIGN: A retrospective data analysis was conducted on patients treated with RFA or TOETVA for unilateral benign TNs between December 2016 and September 2021. Propensity score matching was employed to create comparable groups. Various clinicopathologic parameters, treatment outcomes, and costs were assessed. RESULTS: Of the 2814 nonfunctional thyroid nodules treated during this period, 642 were benign and unilateral. A total of 121 and 100 patients underwent thermal ablation and transoral endoscopic thyroidectomy, respectively. After matching, 84 patients were selected for each group. Both RFA and TOETVA demonstrated low complication rates, with unique complications associated with each procedure. Treatment time (30.8±13.6 vs. 120.7±36.5 min, P <0.0001) was shorter in the RFA group. Patient satisfaction (significant improvement: 89.3% vs. 61.9%, P <0.0001) and cosmetic results (cosmetic score 1-2: 100.0% vs. 54.76%, P <0.0001) favored TOETVA. RFA was found to be less costly for a single treatment, but the cost of retreatment should be considered. The histological diagnoses post-TOETVA revealed malignancies in 9 out of 84 cases, underscoring the significance of follow-up assessments. CONCLUSION: Scarless procedures, RFA and TOETVA, are effective for treating unilateral benign TNs, each with unique advantages and drawbacks. While RFA is cheaper for a single treatment, TOETVA offers superior cosmetic results and patient satisfaction. Further research is needed to evaluate long-term safety and cost-effectiveness. It is crucial to remain vigilant about the possibility of malignancy despite benign cytology pre-treatment.

Intravenous calcitriol administration improves the liver redox status and attenuates ferroptosis in mice with high-fat diet-induced obesity complicated with sepsis.

Obesity aggravates ferroptosis, and vitamin D (VD) may inhibit ferroptosis. We hypothesized that weight reduction and/or calcitriol administration have benefits against the sepsis-induced liver redox imbalance and ferroptosis in obese mice. Mice were fed a high-fat diet for 11 weeks, then half of the mice continued to consume the diet, while the other half were transferred to a low-energy diet for 5 weeks. After feeding the respective diets for 16 weeks, sepsis was induced by cecal ligation and puncture (CLP). Septic mice were divided into four experimental groups: OS group, obese mice injected with saline; OD group, obese mice with calcitriol; WS group, weight-reduction mice with saline; and WD group, weight-reduction mice with calcitriol. Mice in the respective groups were euthanized at 12 or 24 h after CLP. Results showed that the OS group had the highest inflammatory mediators and lipid peroxide levels in the liver. Calcitriol treatment reduced iron content, enhanced the reduced glutathione/oxidized glutathione ratio, upregulated nuclear factor erythroid 2-related factor 2, ferroptosis-suppressing protein 1, and solute carrier family 7 member 11 expression levels. Also, mitochondrion-associated nicotinamide adenine dinucleotide phosphate oxidase 1, peroxisome proliferator-activated receptor-γ coactivator 1, hypoxia-inducible factor-1α, and heme oxidase-1 expression levels increased in the late phase of sepsis. These results were not noted in the WS group. These findings suggest that calcitriol treatment elicits a more-balanced glutathione redox status, alleviates liver ferroptosis, and enhances mitochondrial biogenesis-associated gene expressions. Weight reduction alone had minimal influences on liver ferroptosis and mitochondrial biogenesis in obese mice with sepsis.