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Purpose
Chromogranin A (CgA) and neuron-specific enolase (NSE) are important markers for neuroendocrine tumors; however, the clinical value of combining these markers has not been well studied. In this study, we investigated the utility of each marker individually and in combination for patients with nonfunctional pancreatic neuroendocrine tumors (NF-pNETs).
Patients and Methods
In this study, NF-pNET patients and controls were recruited from December 2011 to March 2016; 784 serum samples from peripheral vein were collected. The clinical characteristics and biomarker values of all the individuals were recorded and analyzed. Tumor burdens were calculated by CT/MRI scan. Receiver-operating characteristic curves were constructed to assess the diagnostic predictive values; sensitivity and specificity were calculated to determine the cut-off value. Therapeutic responses reflected on the changes of the biomarkers’ concentration were assessed by the RECIST criterion. Clinical relations between the prognosis and the biomarker values were also analyzed. Statistical significance was defined as P value less than 0.05.
Results
Among the 167 NF-pNETs patients, 82 were males (49.1%) and the mean age was 50.0 (17.4). The mean CgA values of G1, G2 and G3 NF-pNENs were 75, 121 and 134 μg/L (P < 0.05), respectively. In NF-pNETs, CgA correlated with the WHO tumor grade (WHO G1 vs G2, P < 0.05); the linear regression relationships were found between the tumor burdens (both in pancreas and liver) and CgA concentration (P < 0.001); changes in CgA and NSE concentrations also reflect treatment response (P < 0.001).
Conclusion
CgA and NSE are important diagnostic and follow-up markers in patients with NF-pNETs. The combined monitoring of CgA and NSE possesses more accuracy than individual values of CgA and NSE at predicting prognosis and disease progression.
Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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Objectives
Systemic inflammation markers have been demonstrated to be associated with prognosis in various tumors. In this study, we aimed to assess the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index and the counts of lymphocyte, monocyte and neutrophil in predicting prognosis among patients with resected pancreatic neuroendocrine neoplasms (pNENs).
Methods
A total of 174 patients were included in the study. Univariate and multivariate analyses were performed to evaluate the predictive roles of inflammation markers for relapse-free survival (RFS) and overall survival (OS) in pNEN patients.
Results
The optimal cut-off values of NLR, LMR and lymphocyte count were 1.9, 5.0 and 1.4 × 109/L, respectively, determined by the X-tile software. RFS was found to be significantly longer in patients with NLR ≤1.9 (P = 0.041), LMR >5.0 (P < 0.001) and lymphocyte count >1.4 × 109/L (P = 0.002) in comparison to those with NLR >1.9, LMR ≤5.0 and lymphocyte count ≤1.4 × 109/L, respectively. Multivariate analysis revealed that LMR (hazard ratio 0.30, 95% CI 0.11–0.85, P = 0.023) was an independent predictor for RFS, but not NLR or lymphocyte count. For long-term survival analysis, patients with NLR ≤1.9 (P = 0.016) were found to be associated with favorable OS, but NLR was not an independent factor validated by multivariate analysis.
Conclusions
Preoperative LMR is an independent systemic inflammation marker to predict relapses in pNEN patients who underwent curative resections, whose clinical value needs to be verified in further large sample-based prospective studies.
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Aim
We aim to investigate the clinical characteristics of the rectal NECs and the prognosis-related factors and construct a nomogram for prognosis prediction.
Methods
The data of 41 patients and 1028 patients with rectal NEC were retrieved respectively from our institution and SEER database. OS or PFS was defined as the major study outcome. Variables were compared by chi-square test and t-test when appropriate. Kaplan–Meier analysis with log-rank test was used for survival analysis and the Cox regression analysis was applied. The nomogram integrating risk factors for predicting OS was constructed by R to achieve superior discriminatory ability. Predictive utility of the nomogram was determined by concordance index (C-index) and calibration curve.
Results
In the univariate and multivariate analyses, tumor differentiation, N stage, M stage and resection of primary site were identified as independent prognostic indicators. The linear regression relationship was found between the value of Ki-67 index and the duration of OS (P < 0.05). Furthermore, the independent prognostic factors were added to formulate prognostic nomogram. The constructed nomogram showed good performance according to the C-index.
Conclusions
Contrary to WHO classification guideline, we found that the rectal NEC diseases are heterogeneous and should be divided as different categories according to the pathological differentiation. Besides, the nomogram formulated in this study showed excellent discriminative capability to predict OS for those patients. More advanced predictive model for this disease is required to assist risk stratification via the formulated nomogram.
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Purpose
Emerging evidence suggests G3 pancreatic neuroendocrine neoplasms (pNENs) present heterogeneous morphology and biology. The 2017 WHO classification has introduced a new category of well-differentiated pancreatic neuroendocrine tumors (WD-pNETs) G3, compared with poorly differentiated pancreatic neuroendocrine carcinomas (PD-pNECs) G3. We aim to analysis the demographics and outcomes of patients with resectable 2017 WHO G3 pNENs to facilitate the distinction between two entities.
Methods
The multi-institutional retrospective cohort involving 57 surgically treated patients affected by 2017 WHO G3 pNENs were morphologically identified and clinically analyzed. Patients having WD-pNETs G3 and those having PD-pNECs G3 were compared.
Results
Thirty patients had WD-pNETs and 27 patients had PD-pNECs. The distributions of Ki-67 and mitotic count in patients with PD-pNECs or WD-pNETs showed remarkable disparities. ROC indicated cut-off value of Ki-67 was 45. PD-pNECs were more common in patients with elevated Ki-67 and mitotic count, advanced AJCC TNM stage, vascular invasion, regional lymph-node metastases, elevated NSE and decreased CgA levels compared with WD-pNETs (P < 0.05). The association between 2017 WHO G3 grade and TTR was statistically significant (P < 0.05). Univariate analysis indicated OS rates were associated with morphologic differentiation (WD-pNETs vs PD-pNECs), Ki-67, TNM staging, synchronous distant metastases, initial treatments, vascular invasion, regional lymph nodes metastases, mitotic count and age (P < 0.05). Multivariate analyses illustrated Ki-67, differentiation, TNM staging and vascular invasion were independent predictors (P < 0.05).
Conclusions
PD-pNECs G3 presented malignant biological behavior and dismal outcome compared with WD-pNETs G3. These findings challenge 2010 WHO classification and suggest the categorization can be improved by refined tumor grading.
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Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumor in Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples during July 2021 to August 2022. 2337 (82%) of the cohort possess genetic alterations including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%) and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF positive papillary thyroid cancer (PTC) patients tend to have elder age, smaller tumor size, less vascular invasion, more frequent tumor multifocality and significantly higher cervical lymph node metastatic rate. Mutation at RET gene codon 918 and 634 is strongly correlated with medullary thyroid cancer (MTC), However it did not display more invasive clinical characteristics. TERT positive patients are more likely to have elder age, larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating poor prognosis. Patients with TERT, RET/PTC1 and CHEK2 mutation are more susceptible to lateral lymph node metastasis. In conclusion. NGS can be a useful tool which provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.
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Background
The purpose of this study was to investigate the relationship between circulating zinc α 2-glycoprotein (ZAG), irisin, betatrophin and adiponectin concentrations and metabolic syndrome (MetS) components and to analyze the effects of blood glucose and insulin on these cytokine concentrations in vivo.
Methods
A total of 196 young women, including 78 healthy women and 118 women with MetS components, were recruited for this cross-sectional study. An oral glucose tolerance test and euglycemic-hyperinsulinemic clamp (EHC) were performed in healthy subjects and women with MetS components. An ELISA kit was used to measure serum ZAG, irisin, betatrophin, and adiponectin levels, and their relationship with the MetS components was analyzed.
Results
In women with MetS components, circulating irisin and betatrophin levels were significantly higher than those in the healthy women ((207 (150–248) vs 178 (147–228); P < 0.05) for irisin; (0.51 (0.38–0.63) vs 0.38 (0.23–0.52); P < 0.001) for betatrophin), but circulating ZAG and adiponectin levels were significantly lower (39.8 (26.4–50.4) vs (46.7 (40.6–63.0); P < 0.001) for ZAG; (36.5 (22.0–47.6) vs 41.2 (35.7–54.7); P < 0.01) for adiponectin). FBG, WC, and triglyceride were significantly correlated with the circulating levels of these four cytokines (P < 0.001 or <0.05). All four cytokines were associated with MetS and its components. In response to increasing insulin levels, circulating ZAG concentrations were markedly increased in both healthy subjects and women with MetS components during the EHC. However, serum irisin, betatrophin, and adiponectin levels in both healthy subjects and women with MetS components were significantly reduced compared with baseline.
Conclusion
Serum ZAG, irisin, betatrophin and adiponectin were associated with MetS and might be biomarkers for screening MetS components.
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Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Objective
To compare the efficacy and safety of ethanol ablation (EA) and microwave ablation (MWA) in the treatment of cystic or predominantly cystic thyroid nodules.
Methods
Patients with cystic or predominantly cystic thyroid nodules intervened with EA or MWA were retrospectively enrolled and divided into EA group (n = 30) and MWA group (n = 31). The volume and volume reduction rate (VRR) of thyroid nodules before ablation, and at 3 and 12 months after ablation were compared between the two groups. The effective rate (ER) and incidence of adverse events in both groups were recorded.
Results
The median VRR and ER at 3 months after ablation were significantly higher in EA group than in MWA group (81.30% vs 75.76%, P = 0.011; 76.67% (23/30) vs 51.61% (16/31), P = 0.040), while no significant difference was detected at 12 months (93.39% vs 88.78%, P = 0.141; 86.67% (26/30) vs 87.10% (27/31), P = 0.960). The median VRR of small nodules in EA group was significantly higher than that in MWA group (81.30% vs 71.18%, P = 0.006; 93.40% vs 83.14%, P = 0.032). There was no significant difference of median VRR in medium nodules at final follow-up between MWA and EA group (93.01% vs 89.68%, P = 0.482). Serious adverse events were not reported in both groups.
Conclusion
EA and MWA are both effective and safe in the treatment of cystic or predominantly cystic thyroid nodules. EA is more cost-effective and effective than MWA for small nodules, but it requires more cycles of treatment and may pose a higher risk of postoperative pain compared with MWA.
Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Objective
To assess the long-term efficacy and safety of microwave ablation (MWA) in treating low-risk papillary thyroid microcarcinomas (PTMC) and to identify predictive factors for the postoperative local tumor progression of PTMC.
Methods
A total of 154 low-risk PTMC patients treated with MWA who were followed up for at least 3 months were retrospectively recruited. Ultrasonography was performed after MWA to assess the local tumor progression. Adverse events associated with MWA were recorded. The ablated volume (Va) and initial ablation ratio (IAR) were measured to assess their influences on the recurrence risk of PTMC.
Results
The mean tumor volume of PTMC before MWA was 0.071 (0.039, 0.121) cm3, with a maximum diameter of 0.60 ± 0.18 cm. All PTMC patients were followed up for 6 (3, 18) months. Va increased immediately after MWA, then gradually decreased over time, till significantly smaller at 12 months than that before MWA (P < 0.05). The median volume reduction ratio at 24 months reached 100%, which was maintained during a 60-month follow-up. A total of 7 (4.55%) cases of local tumor progression were recorded during the follow-up. Kaplan–Meier survival analysis revealed that the rate of local tumor progression was significantly lower in PTMC patients with a maximum tumor diameter < 0.70 cm than in those with ≥0.70 cm (P = 0.031). A significant better prognosis was achieved in PTMC patients with IAR ≥ 15 than in those with IAR < 15 (P = 0.015). Sex, age (<55 years) and preoperative thyroid-stimulating hormone (>2.0 mU/L) of PTMC patients were not correlated with local tumor progression.
Conclusion
MWA is an effective therapeutic strategy for low-risk PTMC with high safety. The maximum tumor diameter and IAR are predictive factors for the local tumor progression of PTMC after MWA.
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Insulin-like growth factor 1 (IGF1), also known as somatomedin C, is essential for the regulation of animal growth and development. In many species, the IGF1 gene can be alternatively spliced into multiple transcripts, encoding different pre-pro-IGF1 proteins. However, the exact alternative splicing patterns of IGF1 and the sequence information of different splice variants in sheep are still unclear. In this study, four splice variants (class 1-Ea, class 1-Eb, class 2-Ea, and class 2-Eb) were obtained, but no IGF1 Ec, similar to that found in other species, was discovered. Bioinformatics analysis showed that the four splice variants shared the same mature peptide (70 amino acids) and possessed distinct signal peptides and E peptides. Tissue expression analysis indicated that the four splice variants were broadly expressed in all tested tissues and were most abundantly expressed in the liver. In most tissues and stages, the expression of class 1-Ea was highest, and the expression of other splice variants was low. Overall, levels of the four IGF1 splice variants at the fetal and lamb stages were higher than those at the adult stage. Overexpression of the four splice variants significantly increased fibroblast proliferation and inhibited apoptosis (P < 0.05). In contrast, silencing IGF1 Ea or IGF1 Eb with siRNA significantly inhibited proliferation and promoted apoptosis (P < 0.05). Among the four splice variants, class 1-Ea had a more evident effect on cell proliferation and apoptosis. In summary, the four ovine IGF1 splice variants have different structures and expression patterns and might have different biological functions.
