Are single nucleotide polymorphisms in the IL-2 gene biomarkers for Hashimoto's thyroiditis?

Background and aims: Hashimoto's thyroiditis (HT) is an autoimmune disorder that can lead to hypothyroidism. The pathophysiology of HT involves the production of antithyroid antibodies that attack the thyroid tissue, causing inflammation and progressive fibrosis. Recent studies demonstrated a strong correlation between Interleukin-2 (IL-2) levels and the development of autoimmune diseases, suggesting that this cytokine may play a crucial role in the pathogenesis of HT. Methods: In this study, we determined the presence of the point mutation +114T/G in the IL-2 gene in patients with HT compared with a control group, and also the serum level of anti-thyroid peroxidase (TPOAbs) and anti-thyroglobulin (TgAbs) antibodies in HT patients with vs. without the mutation. The sequences of the IL-2 gene obtained from subjects were determined by the Sanger sequencing method. Results: Our study did not reveal that the +114T/G polymorphism of the IL-2 gene is a susceptibility or protective factor for HT. No significant correlations were observed between the reference genotype, hetero- and homozygous +114T/G polymorphism and TPOAbs, respectively TgAbs serum levels in HT patients. Conclusions: Further studies of more cases are needed to identify more polymorphisms in the IL-2 gene and study their correlations with HT.

Impact on Long-term Survival of a Standardized Histopathological Protocol on the R1 Incidence in Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma.

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is a pathology with a very poor prognostic, the only curative treatment option being surgery, in association with chemotherapy. This study aims to assess the influence that the use of a standardized pathology report after a pancreaticoduodenectomy (PD) has on the R1 margins rate and the impact that this has on long term survival. Material and Methods: We included 116 patients admitted to the Regional Institute of Gastroenterology and Hepatology Prof. Dr. O. Fodor Cluj Napoca, who underwent PD for PDAC (Pancreatic Ductal Adenocarcinoma) between January 2012 and May 2017. We divided them in two groups: 59 patients for which a nonstandardized histopathological protocol was used and 57 patients for which a standardized protocol was implemented. We considered a margin to be R1 when there were tumor cells at ¤ 1 mm from the resection margin. Results: The R1 percentage in the first group of patients was of 39%, while the R1 resection rate in the second group was of 68.4%. The median survival rate was similar in the two groups, with no statistically significant difference between them, but in the prospective study when comparing R0 vs R1 margins there was a statistically differences in 5 year OS with a p-value = 0.03. Conclusion: The use of a standardized pathology report reveals a significant increase in R1 resection rates. Also study revealed not only increasing R1 incidence when using a standardized histopathology report, but also that those margins (R1) playing a determinant role in 5-year OS. The mesopancreas is the most frequently R1 resection margin.

Microscopic Positive Margins in Gastric Adenocarcinoma Following Oncological Resection: Prognostic Factors and Long-Term Survival.

BACKGROUND: In the context of gastric cancer, surgical resection stands as the sole curative treatment. Central to influencing overall survival are the resection margins. This research aims to identify the factors influential in determining microscopically positive resection margins (R1) and to evaluate overall survival. METHODS: Our study encompassed 549 patients diagnosed with adenocarcinoma of the stomach who underwent curative-intent surgery between January 2011 and December 2021 in our Surgery Department. We investigated the incidence of positive margins (R1) and their impact on survival rates, as well as the determinants of R1. The standardization of R1 involved ensuring a margin distance of less than 1 mm from the tumor line to the margin. RESULTS: The incidence of R1 margins was 13.29% (73 patients). Among these, proximal R1 margins were observed in 29 patients (39.72%), while 49 cases (67.12%) presented circumferentially positive margins, with 20 cases (27.39%) exhibiting distally positive margins. Nineteen patients (26.02%) had two R1 margins, and 3 patients had all resection margins microscopically positive (4.10%). Factors such as tumor dimension, invasion of other organs, pT stage, pN stage, pL1 stage, pV1 stage, pPn stage, Lauren type, and tumoral grading demonstrated significance (p < 0.01) in the occurrence of positive R1 margins. CONCLUSION: Tumor dimension, invasion of other organs, pT stage, pN stage, pL1 stage, pV1 stage, pPn stage, Lauren type, and tumoral grading could be regarded as factors for predicting microscopically positive margins. Moreover, positive resection margins have a detrimental impact on overall survival.

Inflammatory Ratios as Survival Prognostic Factors in Resectable Gastric Adenocarcinoma.

BACKGROUND: The purpose of the study was to assess the relationship between inflammatory biomarkers (NLR-neutrophil-to-lymphocyte ratio, PLR-platelet-to-lymphocyte ratio, LMR-lymphocyte-to-monocyte ratio, SII-systemic immune-inflammation index) and overall survival in gastric cancer patients. METHODS: Over a six-year period (2016-2021), we conducted a longitudinal retrospective cohort research on 549 patients with resectable stomach adenocarcinoma. The overall survival was determined using the univariate and multivariate COX proportional hazards models. RESULTS: The age of the cohort varied between 30 and 89 years old, with an average age of 64.85 ± 10.51 years. Four hundred seventy-six patients (86.7%) had R0 resection margins. Eighty-nine (16.21%) subjects received neoadjuvant chemotherapy. Two hundred sixty-two (47.72%) patients died during the follow-up period. The median survival time in the cohort was 390 days. A significantly lower (p = 0.029-Logrank test) median survival was observed for R1 resections (355 days) in comparison with R0 resections (395 days). Significant differences in survival were observed regarding tumor differentiation, tumoral (T), and node (N) stage. No differences in survival were observed between the low or high value of inflammatory biomarkers (dichotomized by median value in the sample). In the COX univariate and multivariate regression models, elevated NLR proved an independent prognostic factor for lower overall survival [HR = 1.068, (95% CI 1.011-1.12)]. In this study, the other inflammatory ratios (PLR, LMR, and SII) did not prove as prognostic factors for gastric adenocarcinoma. CONCLUSIONS: In resectable gastric adenocarcinoma, elevated NLR before surgery was associated with lower overall survival. PLR, LMR, and SII had no prognostic value for the patient's survival.

Chitotriosidase and Neopterin as Two Novel Potential Biomarkers for Advanced Stage and Survival Prediction in Gastric Cancer-A Pilot Study.

Gastric cancer is the fifth type of neoplasia most frequently diagnosed and the fourth cause of death among other cancers. Prevalence is around two times higher for males than females. Chitotriosidase and neopterin are two molecular biomarkers with potential diagnostic and prognostic use in malignant pathology. We conducted a longitudinal prospective cohort study on thirty-nine patients with gastric adenocarcinoma, with a male-to-female ratio of 1.78 and an average age of 64.3 ± 9.97 years. No statistically significant differences in biomarker levels at presentation were observed between curative-intent surgery (28 patients) and advanced cases, suited only for palliative procedures (11 patients). Biomarker values were not significantly different for the advanced T stage and the presence of metastasis (p > 0.05-Mann Whitney test). The patients that died in the first 30 days after surgery did not present significantly different values at baseline, in comparison with those that had longer survival times, though a significant cut-off value was observed for chitotriosidase activity at 310 nmol/mL/h [AUC (area under the curve) = 0.78; 95% CI (0.61-0.92)]. The cut-off values corresponding to death after the first year, tumor invasion, and metastasis were not statistically significant. In the COX multivariate model, neopterin did not validate itself as a prognostic biomarker, however, chitotriosidase activity before surgery was significantly associated with overall survival (HR = 1.0038, p = 0.03). We conclude that chitotriosidase may have the potential to improve the prognostic model for gastric adenocarcinoma.

Chitotriosidase and Neopterin as Potential Biomarkers for the Evaluation of Complicated Cholecystitis-A Pilot Study.

Gallstones are a common surgical pathology. Laparoscopic cholecystectomy represents the elective treatment. Complicated cases can increase the rate of conversion, the duration, and the difficulty of the intervention, along with the hospitalization period. A prospective cohort study was conducted on 51 patients with gallstones. Only subjects with normal renal, pancreatic, and hepatic functions were included. The severity of cholecystitis was evaluated by considering the ultrasound examination, intraoperative findings, and pathology report. We evaluated two potential biomarkers, namely neopterin and chitotriosidase, by comparing their levels before and after the intervention for chronic (n = 36) and complicated (n = 15) cases, as well as their eventual association with the hospitalization period. Subjects with complicated cholecystitis had significantly higher (p = 0.01) neopterin levels at presentation (16.82 nmol/L vs. 11.92 nmol/L, median values), but the differences in chitotriosidase activity between complicated (170.00 nmol/mL/h) and chronic (160.00 nmol/mL/h) cases were not significant (p = 0.66). Patients with neopterin levels above the cut-off value 14.69 nmol/L had a 3.34 times higher risk of complicated cholecystitis. Twenty-four hours after the laparoscopic cholecystectomy, the differences in neopterin level and chitotriosidase activity between chronic and complicated cases were not significant. A significant decrease in chitotriosidase activity was observed after the intervention, only for complicated cases (190 nmol/mL/h vs. 145 nmol/mL/h, p = 0.007); for neopterin, the postoperative decrease was not statistically significant (19.42 nmol/L vs. 10.92 nmol/L, p = 0.06). No significant association with the hospitalization period was observed. Neopterin may be a useful biomarker for complicated cholecystitis, and chitotriosidase may have prognostic utility in early patient follow-up.

Klatskin Tumor: A Survival Analysis According to Tumor Characteristics and Inflammatory Ratios.

Background and Objectives: The aim was to evaluate the association of inflammatory biomarkers with resectability and overall survival in hilar cholangiocarcinoma. Materials and Methods: We conducted a retrospective cohort study over 72 consecutive surgical cases of Klatskin tumor over an 11-year period. The sample was divided into two groups: 42 surgical resection cases and 30 unresectable tumors. Values of inflammatory ratios were compared according to the resectability. Log-rank test, univariate, and multivariate Cox proportional hazards models were used to evaluate the overall survival. Results: Subjects were between 42−87 years old (average age of 64.91 ± 9.15 years). According to the procedure: 58.33% benefited from resection (with a 30.95% R0 resection rate) and 41.66% had palliative surgery. Elevated NLR (neutrophil to lymphocyte ratio), PLR (platelet to lymphocyte ratio), and SII (systemic immune-inflammation index), and lower LMR (lymphocyte to monocyte ratio) at admission were associated with unresectable tumors (p < 0.01). For the multivariate Cox proportional hazard models, increased absolute values of NLR, PLR, and SII were associated with lower survival; no differences were observed for LMR absolute value. The cut-off value of NLR ≥ 6 was associated with lower survival. The median survival time for all subjects was 442 days, with 774 days for the resection group and 147 days for the group with palliative surgery. Conclusions: In hilar cholangiocarcinoma, inflammatory ratios are associated with tumor resectability. Tumor excision conferred an important advantage in survival. Elevated NLR, PLR, and SII values at admission significantly increased the hazard ratio. LMR had no influence on survival.