Do PFCAs drive the establishment of thyroid cancer microenvironment? Effects of C6O4, PFOA and PFHxA exposure in two models of human thyroid cells in primary culture.

BACKGROUND: Exposure to environmental pollutants is suspected to be one of the potential causes accounting for the increase in thyroid cancer (TC) incidence worldwide. Among the ubiquitous pollutants, per-polyfluoroalkyl substances (PFASs), were demonstrated to exert thyroid disrupting effects. Perfluoroalkyl carboxylates (PFCAs) represent a subgroup of PFAS and include perfluoro carboxylic acids (PFOA and PFHxA) and perfluoropolyether carboxylic acid (C6O4). The potential relationship between exposure to PFCAs and TC was not yet fully elucidated. This in vitro study investigated whether certain PFCAs (C6O4, PFOA, and PFHxA) can influence the composition of TC microenvironment. METHODS: Two models of normal thyroid cells in primary cultures: Adherent (A-NHT) and Spheroids (S-NHT) were employed. A-NHT and S-NHT were exposed to C6O4, PFOA or PFHxA (0; 0.01; 0.1, 1; 10; 100; 1000 ng/mL) to assess viability (WST-1 and AV/PI assay), evaluate spherification index (SI) and volume specifically in S-NHT. CXCL8 and CCL2 (mRNA and protein), and EMT-related genes were assessed in both models after exposure to PFCAs. RESULTS: PFHxA reduced the viability of both A-NHT and S-NHT. None of the PFCAs interfered with the volume or spherification process in S-NHT. CXCL8 and CCL2 mRNA and protein levels were differently up-regulated by each PFCAs, being PFOA and PFHxA the stronger inducers. Moreover, among the tested PFCAs, PFHxA induced a more consistent increase in the mRNA levels of EMT-related genes. CONCLUSIONS: This is the first evaluation of the effects of exposure to PFCAs on factors potentially involved in establishing the TC microenvironment. PFHxA modulated the TC microenvironment at three levels: cell viability, pro-tumorigenic chemokines, and EMT-genes. The results provide further evidence of the pro-tumorigenic effect of PFOA. On the other hand, a marginal effect was observed for C6O4 on pro-tumorigenic chemokines.

The American Thyroid Association risk classification of papillary thyroid cancer according to presurgery cytology.

OBJECTIVE: To compare the American Thyroid Association (ATA) risk staging of histologically proven papillary thyroid cancer (PTC) in patients who received a presurgery cytologic result of either indeterminate thyroid nodules (ITNs, Bethesda III/IV) or suspicious for malignancy/malignant (TIR 4/5, Bethesda V/VI). METHODS: Clinical, ultrasonographic, cytological data from patients with histologically diagnosed PTC were retrospectively collected. RESULTS: Patients were stratified according to the preoperative fine-needle aspiration cytology into 2 groups: 51 ITNs (TIR3A/3B) and 118 suspicious/malignant (TIR 4/5). Male/female ratio, age, and presurgery TSH level were similar between the 2 groups. At ultrasound, TIR 4/5 nodules were significantly more frequently hypoechoic (P = .037), with irregular margins (P = .041), and with microcalcifications (P = .020) and were more frequently classified as high-risk according to the European Thyroid Imaging and Reporting Data System (EU-TIRADS; P = .021). At histology, the follicular PTC subtype was significantly more prevalent among ITNs while classical PTC subtype was more frequent in TIR 4/5 group (P = .002). In TIR 4/5 group, a higher rate of focal vascular invasion (P < .001) and neck lymph node metastasis (P = .028) was observed. Intermediate-risk category according to ATA was significantly more frequent in TIR 4/5 group while low-risk category was more frequently found among ITNs (P = .021), with a higher number of patients receiving radioiodine in TIR 4/5 group (P = .002). At multivariate logistic regression, having a TIR 4/5 cytology was associated with a significant risk of having a higher ATA risk classification as compared to ITN (OR 4.6 [95% CI 1.523-14.007], P = .007), independently from presurgery findings (nodule size at ultrasound, sex, age, and EU-TIRADS score). CONCLUSIONS: Papillary thyroid cancers recorded among ITNs are likely less aggressive and are generally assessed as at lower risk according to ATA classification.

Liposarcoma of spermatic cord mimicking an inguinal hernia A case report and review of the literature.

AIM: Liposarcoma of the spermatic cord (LSC) is a tumour often mistaken for common inguinal swelling as hernia and the aim of this work is to present our case with a review of the Literature to define the management of this rare condition. MATERIAL OF STUDY: A systematic review has been realised, considering English language articles published on Pubmed, between 1956 and 2022, using as key words "Liposarcoma of the spermatic cord". RESULTS: 160 studies described 420 cases of LSC and in 40 cases the patient had undergone surgery with an initial diagnosis of inguinal hernia. DISCUSSION: LSC is a very rare entity of genitourinary malignancies, occurring more often in the spermatic cord and diagnosis can be difficult. Our case and Literature data confirm the role of imaging in not conventional inguinal swelling, to avoid diagnostic mistakes and to define preoperatively the correct surgical management. CONCLUSIONS: Imaging is mandatory in case of diagnostic doubt. The recommended treatment is a radical high orchiectomy with clear margins. A long follow-up period is necessary to detect a local recurrence which may occur even several years after the primary therapy. KEY WORDS: Inguinal swelling, Liposarcoma, Spermatic cord.

Pre-surgery dietician counseling can prevent post-thyroidectomy body weight gain: results of an intervention trial.

PURPOSE: It is widely accepted that patients experience weight gain after total thyroidectomy, and preventive measures should be recommended. METHODS: A prospective study was designed to assess the efficacy of a dietetic intervention to prevent post-thyroidectomy weight gain in patients undergoing surgery for both benign and malignant thyroid conditions. Patients undergoing total thyroidectomy were prospectively and randomly assigned to receive a personalized pre-surgery diet counseling (GROUP A) or no intervention (GROUP B), according to a 1:2 ratio. All patients underwent follow-up with body-weight measurement, thyroid function evaluation and lifestyle and eating habits assessment at baseline (T0), 45 days (T1) and 12 months (T2) post-surgery. RESULTS: The final study group encompassed 30 patients in Group A and 58 patients in Group B. The two groups were similar in terms of age, sex, pre-surgery BMI, thyroid function and underlying thyroid condition. The evaluation of body weight variations showed that patients in Group A did not experience significant body weight changes at either T1 (p = 0.127) nor T2 (p = 0.890). At difference, patients in Group B underwent a significant body weight increase from T0 to both T1 (p = 0.009) and T2 (p = 0.009). TSH levels were similar in the two groups, both at T1 and T2. Lifestyle and eating habits questionnaires failed to register any significant difference between the two groups, apart from an increase in sweetened beverages consumption in Group B. CONCLUSIONS: A dietician counseling is effective in preventing the post-thyroidectomy weight gain. Further studies in larger series of patients with a longer follow-up appear worthwhile.

Is there a relationship between different types of prior bariatric surgery and post-thyroidectomy hypocalcemia?

BACKGROUND: Hypocalcemia is a common complication after total thyroidectomy (TT). A history of bariatric surgery has been identified as a risk factor for this complication. This study aimed to assess the risk of hypocalcemia post TT in patients with a history of obesity procedures: laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), and laparoscopic gastric banding (LAGB). METHODS: We compared the risk of hypocalcemia post TT (serum calcium levels <8 mg/dL) between patients with restrictive (LSG and LAGB), malabsorptive (RYGB), and patients without a history of obesity surgery. Hypoparathyroidism was considered permanent if the plasma parathyroid hormone (PTH) levels at 6 months were less than 15 pg/mL (normal range: 15-65 pg/mL) and the patient still required oral calcium (calcium carbonate) and vitamin D supplementation, in addition to the supplements that were taken routinely before thyroidectomy. RESULTS: From the 13,242 patients who underwent TT from 2006 to 2018, 90 patients (0.7%) had a history of bariatric surgery: 35 LAGB, 29 LSG, and 26 RYGB. The risk of hypocalcemia was higher in RYGB patients (50%, n=13) than in LAGB (17.1%, n=6) or LSG patients (20.6%, n=6) (P=0.003). Furthermore, hypocalcemia risk was similar between patients with a history of restrictive procedures (18.8%, 12/64) and patients with no history of bariatric surgery (17.2%, 2,268/13,152) (P=0.4). Permanent hypoparathyroidism was observed in one and 6 patients from the LAGB and RYGB groups, respectively; however, it was not observed in any patient from the LSG group. CONCLUSIONS: RYGB is a risk factor for hypocalcemia post TT, while restrictive bariatric procedures are not.

Robotic approach for partial adrenalectomy.

Although safe and feasible, partial adrenalectomy is not a widespread procedure. Endorsement of robotic technologies and fluorescence techniques in adrenal surgery might help develop partial adrenalectomy and could avoid unnecessary total adrenalectomies. When performed in selected cases, partial adrenalectomy is associated with good postoperative outcomes comparable with those reported after total adrenalectomy. It has been hypothesized that one of the advantages of the robotic approach in adrenal-sparing surgery is to reduce manipulation of the gland allowing preservation of the vascularization of the residual adrenal, overcoming some limits when performing a laparoscopic conventional approach. A major drawback of the robotic surgery is its cost, but the overcost due to the use of the robotic system could be balanced by the execution of a high number of partial adrenalectomies leading to fewer life-long replacement steroid treatment. Partial adrenalectomy could become the recommended management for small benign and hormonal active adrenal tumors. Indocyanine green fluorescence (IGF) also seems to be a useful technique to help surgeons identify the adrenal gland and to locate small tumors from the normal adrenal tissue in difficult patients. It is likely that the use of a robotic approach associated with IGF may extend indications of partial adrenalectomy in the years to come.

Sleeve gastrectomy and crural repair in obese patients with gastroesophageal reflux disease and/or hiatal hernia.

BACKGROUND: Gastroesophageal reflux disease (GERD) with or without hiatal hernia (HH) is now recognized as an obesity-related co-morbidity. Roux-en-Y gastric bypass has been proved to be the most effective bariatric procedure for the treatment of morbidly obese patients with GERD and/or HH. In contrast, the indication for laparoscopic sleeve gastrectomy (SG) in these patients is still debated. Our objective was to report our experience with 97 patients who underwent SG and HH repair (HHR). The setting was a university hospital in Italy. METHODS: From July 2009 to December 2011, 378 patients underwent a preoperative workup for SG. In 97 patients, SG was performed with HHR. The clinical outcome was evaluated considering GERD symptom resolution or improvement, interruption of antireflux medications, and radiographic evidence of HH recurrence. RESULTS: Before surgery, symptomatic GERD was present in 60 patients (15.8%), and HH was diagnosed in 42 patients (11.1%). In 55 patients (14.5%), HH was diagnosed intraoperatively. The mean follow-up was 18 months. GERD remission occurred in 44 patients (73.3%). In the remaining 16 patients, antireflux medications were diminished, with complete control of symptoms in 5 patients. No HH recurrences developed. "De novo" GERD symptoms developed in 22.9% of the patients undergoing SG alone compared with 0% of patients undergoing SG plus HHR. CONCLUSION: SG with HHR is feasible and safe, providing good management of GERD in obese patients with reflux symptoms. Small hiatal defects could be underdiagnosed at preoperative endoscopy and/or upper gastrointestinal contrast study. Thus, a careful examination of the crura is always recommended intraoperatively.

Cardiac remodeling in obese patients after laparoscopic sleeve gastrectomy.

BACKGROUND: Obesity is associated with high morbidity and represents an increasing health care problem worldwide. Laparoscopic sleeve gastrectomy (LSG) has been used effectively for weight loss and co-morbidity remission. In this retrospective study, we evaluated cardiac reverse remodeling at medium-term follow-up by echocardiography, the amount of cardiovascular medications, and the impact of co-morbidities after sleeve gastrectomy. METHODS: Altogether, 16 obese patients (4 men, 12 women; 46.4 ± 10.3 years) underwent complete clinical evaluation, laboratory tests, and color Doppler/tissue Doppler imaging echocardiography preoperatively and 12-20 months after bariatric surgery. RESULTS: Body weight (mean body mass index) was significantly reduced (from 44.8 ± 8.0 to 31.2 ± 7.8 kg/m2; p = 0.001). Lipid profile significantly improved: total cholesterol and triglycerides decreased (respectively: 215.5 ± 53.8 vs. 205.3 ± 46.6 mg/dl and 184.9 ± 109.3 vs. 116.1 ± 49.9 mg/dl, both p ≤ 0.05), and high-density lipoprotein increased (43.1 ± 10.9 vs. 51.4 ± 12.8 mg/dl, p = 0.005). Systolic blood pressure significantly decreased (from 133.0 ± 17.1 to 120.6 ± 13.7 mmHg; p = 0.04). Diabetes remission was complete in five of six patients (83%) and sleep apnea in four of five (80 %). Echocardiography showed significantly reduced interventricular septum and posterior wall thickness (11.3 ± 1.8 to 9.4 ± 2.1 mm and 10.4 ± 1.7 to 8.6 ± 1.9 mm, respectively; both p < 0.007) and reduced left ventricular mass (absolute value and indexed by height, respectively: 222.41 ± 78.2 to 172.75 ± 66.3 g (p = 0.003) and 55.9 ± 14.3 to 43.8 ± 17.2 g/m(2.7) (p = 0.0004). Antihypertensive drug intake was significantly reduced (p = 0.03), as shown by the 10-year Framingham Risk Score (from 14.2 ± 9.3 to 8.3 ± 9.5%, p = 0.003). CONCLUSIONS: Sleeve gastrectomy is associated with marked improvement in terms of weight loss, lipid profile, type 2 diabetes, sleep apnea, hypertension, and left ventricular hypertrophy, with a significantly reduced Framingham Risk Score.

Ten-year duration of type 2 diabetes as prognostic factor for remission after sleeve gastrectomy.

BACKGROUND: Several studies have demonstrated a high rate of type 2 diabetes mellitus (T2DM) resolution after sleeve gastrectomy. Different prognostic factors have been hypothesized for T2DM remission after bariatric surgery. Our objectives were to analyze the role of T2DM duration as an independent prognostic factor for remission. METHODS: From January 2008 to September 2010, 56 obese patients with T2DM underwent sleeve gastrectomy. Group A consisted of 16 patients who had lived with T2DM for >10 years (12 women and 4 men, mean body mass index 42.7 kg/m2). Group B included 40 obese patients who had lived with T2DM for <10 years (29 women and 11 men, mean body mass index 44.9 kg/m2). RESULTS: In group A, 43.7% were treated with oral hypoglycemics, 6.3% with insulin, and 50% with oral hypoglycemics and insulin. In group B, 87.5% were treated with oral hypoglycemics, 5% with dietary therapy, and 7.5% with insulin. The preoperative average glycemia, glycosylated hemoglobin, and C-peptide value was 206.2 mg/dL, 9.5%, and 2.8 µg/L in group A and 134 mg/dL, 7.1%, and 4.5 µg/L in group B, respectively (P < .05 for all). The T2DM remission rate in all 56 patients was 80.3%. However, in group B, the resolution rate was 100%, but in group A, the resolution rate was 31%. Patients without complete remission were more sensitive to lower doses of antidiabetic drugs. CONCLUSION: Sleeve gastrectomy is effective in the treatment of obese patients with T2DM. The duration of T2DM seems to be of paramount importance as a prognostic factor, with 10 years representing a cutoff between a 100% rate of remission and significantly lower rates of remission.

Initial experience with laparoscopic crural closure in the management of hiatal hernia in obese patients undergoing sleeve gastrectomy.

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) and/or hiatal hernia (HH) is significantly increased in morbidly obese patients. Laparoscopic bariatric procedures such as gastric banding (LGB) and Roux-en-Y gastric bypass have been shown to improve both obesity and reflux symptoms. The aim of this paper is to evaluate the effectiveness of laparoscopic sleeve gastrectomy (LSG) and hiatal hernia repair (HHR) for the treatment of obesity complicated by HH. METHODS: From October 2008, six patients underwent HHR in addition to LSG. Clinical outcomes have been evaluated in terms of GERD symptoms improvement or resolution, interruption of antireflux medication, and X-ray evidence of HH recurrence. RESULTS: Symptomatic HH was diagnosed preoperatively in four patients. In two additional patients, HH was asymptomatic and it was diagnosed intraoperatively. Prosthetic reinforcement of crural closure was performed in two symptomatic cases with a HH >5 cm. Mortality was nil and no complications occurred. After a mean follow-up of 4 months, GERD symptoms resolution occurred in three patients, while the other patient reported an improvement of reflux. Body mass index had fallen from 43.4 to 36.2 kg/m(2). A small recurrence in the patient with persistence of reflux symptoms has been radiologically reported. CONCLUSIONS: Laparoscopic crural closure in addition to LSG could represent a valuable option for the synchronous management of morbid obesity and HH, providing good outcomes in terms of weight loss and GERD symptoms control.