Long-term survival outcomes of pediatric adrenal malignancies: An analysis with the upstaged SEER registry during 2000-2019.

Objective: To investigate the clinicopathological characteristics and long-term survival outcomes of pediatric adrenal malignancies. Method: This study retrospectively analyzed children with pathologically confirmed pediatric adrenal malignancies from Surveillance, Epidemiology, and End Results Database from 2000 to 2019. Kaplan-Meier curve was used to assess the overall survival (OS) and cancer-special survival (CSS), and the Log-Rank method was used to calculate statistical differences. Cox proportional hazards model and Fine-and-Grey model were used to calculate the hazard ratio (HR) of all-cause mortality risk and the sub-distribution HR (sHR) of disease-specific mortality risk, respectively, and their corresponding 95% confidence intervals (CI). Results: 1601 children were included in the study in which 1335 (83.4%) neuroblastoma, 151 (9.4%) ganglioneuroblastoma, 89 (5.6%) adrenocortical carcinoma, and 26 (1.6%) were diagnosed with other types malignancies. Metastatic disease accounted for the largest proportion (69.3%), and the proportion of metastases diagnosed by neuroblastoma was higher than that of adrenocortical carcinoma and ganglioneuroblastoma (73.9% vs. 45.7% vs. 47.2%). The 5-year OS and CSS of all cohort were 69.5% and 70.5%, respectively. Adrenal cortical carcinoma had the worst prognosis, with 5-year OS and CSS of 52.5% and 53.1%, respectively. Patients in recent years had no better OS and CSS than in previous years at diagnosis. The tumor stage remained the main prognostic predictor. Compared to metastatic adrenal tumors, the risk of all-cause mortality (adjusted HR: 0.12, 95% CI: 0.06-0.25, P < 0.001) and the risk of disease-specific mortality (adjusted sHR: 0.11, 95% CI: 0.05-0.25, P<0.001) was significantly lower for patients with localized diseases. Additionally, higher age, adrenal cortical carcinoma, and lack of complete tumor resection are independent risk factors for poor prognosis. Furthermore, it was found that the prognosis of patients who received chemotherapy was worse than those who did not, mainly because the former mostly had metastasis at the presentation and complete resection of the tumor cannot be achieved. Conclusion: The clinicopathological characteristics of pediatric adrenal malignancies have not changed significantly in the past two decades, while the prognosis of patients has improved. Early diagnosis of disease and complete resection of local tumors are the keys to improving prognosis.

Comparison of Metaraminol, Phenylephrine, and Norepinephrine Infusion for Prevention of Hypotension During Combined Spinal-Epidural Anaesthesia for Elective Caesarean Section: A Three-Arm, Randomized, Double-Blind, Non-Inferiority Trial.

BACKGROUND: A direct comparison of phenylephrine, metaraminol, and norepinephrine in preventing hypotension during spinal anaesthesia for elective caesarean section has never been made. PATIENTS AND METHODS: Seventy-five parturients scheduled for elective caesarean section were randomly assigned into the three groups. After spinal anaesthesia induction, patients received a bonus dose of vasopressor (norepinephrine 4ug, phenylephrine 50ug, or metaraminol 250ug) combined with continuous infusion (norepinephrine 8ug/mL, phenylephrine 100ug/mL, or metaraminol 500ug/mL) at a rate of 30 mL/h to prevent hypotension. The primary outcome was umbilical arterial (UA) pH and other intraoperative data were also recorded. RESULTS: The UA pH was 7.32±0.03 for metaraminol, 7.31±0.03 for phenylephrine, and 7.31±0.03 for norepinephrine. The 95% CI of MD was -0.011 to 0.026 comparing metaraminol with norepinephrine and 0.0181 to 0.0182 comparing phenylephrine with norepinephrine. Both lower bounds of the 95% CI of MD were above the predetermined lower boundary of clinical non-inferiority of -0.03, indicating both metaraminol and phenylephrine were non-inferior to norepinephrine. Moreover, the incidence of hypotension was lower in metaraminol compared with norepinephrine (P = 0.01). However, the incidence of hypertension was significantly lower in both phenylephrine and metaraminol compared with norepinephrine. CONCLUSION: Both metaraminol and phenylephrine were non-inferior to norepinephrine with respect to neonatal UA pH when used as a bolus and continuous infusion to prevent hypotension during combined spinal-epidural anaesthesia for elective caesarean section.

Human papillomavirus DNA, HPV L1 capsid protein and p16INK4a protein as markers to predict cervical lesion progression.

OBJECTIVES: Cervical cancer is the most common malignant tumors in women leading to serious morbidity and mortality worldwide, especially among developing countries. A main cause of the disease is the high-risk human papillomavirus (HR-HPV) infection. HSIL usually progress to cervical cancer, and low-grade lesions, including LSIL and ASCUS, mostly turn to normal or benign lesions, but there are still a small number of patients who will progress to HSIL. Up to now there is no efficient biomarker clinically available to predict people with high risk to progress into HSIL. This study was conducted to evaluate the value of human papillomavirus (HPV) DNA, p16INK4a protein, and HPV L1 capsid protein in predicting HSIL and minimizing unnecessary colposcopy treatments. METHODS: 1222 patients with HR-HPV infection or with abnormal Thinprep cytologic test (TCT) were chosen to conduct colposcopy in the cervical out-patient clinic of Shanghai First Maternity and Infant Hospital affiliated to Shanghai Tongji University from June 2014 to January 2017. TCT, cervical biopsy, HPV DNA and HPVL1 were performed on all patients. 110 patients were selected to detect p16INK4a protein. Hybrid capture 2 (HC-2) was used to detect HPV DNA, and their subgroups using gene typing system. Immunohistochemical technology was used to detect HPV L1 and p16. RESULTS: HPV DNA was positive in 1097 cases, with the positive rate of 89.7% (1097/1222). In particular, the positive expression rates of HPV DNA were 82.3, 95.7, 96.6 and 100% in Normal/CC, LSIL, HSIL and cervical cancer groups, respectively (p < 0.001). HPV L1 was negative in 781 cases with HR-HPV infection, and the overall negative rate is 71.1%. In patients with Normal/CC, LSIL and HSIL, the negative expression rates of HPV L1 were 91.3, 40 and 81.2%, respectively (p value < 0.001). In the 110 patients, HPV L1 was negative in 98.1% (53/54) of Normal/CC, 42.9% (12/28) of LSIL and 85.1% (23/27) of HSIL (p value = 0.0043). P16-positive rates in patients with Normal/CC, LSIL and HSIL were 33.3% (18/54), 75% (21/28) and 96.2% (26/27), respectively (p value < 0.001). 18 out of 28 cases express low positive (+) in LSIL, 25 out of 27 cases express strong positive (3+) in HSIL. Patients with L1(-) p16(+) including 18.5% (10/54) of normal/cervicitis, 60.7% (17/28) of LSIL and 85.1% (23/27) of HSIL (p value < 0.005). Furthermore, patients with L1(-) p16(1+) included 37% (10/27) of normal/cervicitis 59.3% (16/27) of LSIL and 3.7% (1/27) of HSIL; patients with L1(-) p16(2+) consisted of 0% of normal/cervicitis/LSIL and 100% (1/1) of HSIL; patients with L1(-) p16(3+) were composed of 0% of normal/cervicitis, 4.5% (1/22) of LSIL and 95.5% (21/22) of HSIL (p value < 0.005) (Table 6). CONCLUSION: With the increase in the degree of the cervical lesions, the expression of HPV DNA and p16 is up-regulated while HPV L1 protein is down-regulated. HPV DNA, HPV L1 and p16 are useful markers for the prediction of HSIL. Combined detection of these three markers has important potential to predicting HSIL and minimizing unnecessary colposcope examination.

HPV16 integration probably contributes to cervical oncogenesis through interrupting tumor suppressor genes and inducing chromosome instability.

BACKGROUND: The integration of human papilloma virus (HPV) into host genome is one of the critical steps that lead to the progression of precancerous lesion into cancer. However, the mechanisms and consequences of such integration events are poorly understood. This study aims to explore those questions by studying high risk HPV16 integration in women with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (SCC). METHODS: Specifically, HPV integration status of 13 HPV16-infected patients were investigated by ligation-mediated PCR (DIPS-PCR) followed by DNA sequencing. RESULTS: In total, 8 HPV16 integration sites were identified inside or around genes associated with cancer development. In particular, the well-studied tumor suppressor genes SCAI was found to be integrated by HPV16, which would likely disrupt its expression and therefore facilitate the migration of tumor. On top of that, we observed several cases of chromosome translocation events coincide with HPV integration, which suggests the existence of chromosome instability. Additionally, short overlapping sequences were observed between viral derived and host derived fragments in viral-cellular junctions, indicating that integration was mediated by micro homology-mediated DNA repair pathway. CONCLUSIONS: Overall, our study suggests a model in which HPV16 might contribute to oncogenesis not only by disrupting tumor suppressor genes, but also by inducing chromosome instability.

Distribution of HPV genotypes in Shanghai women.

OBJECTIVE: To study the Distribution of HPV genotypes in Shanghai women. DESIGN: Cohort study. SETTING: Shanghai First Maternity and Infant Hospital affiliated with Tongji University. POPULATION: Patients those attended in the cervical disease diagnosis and treatment center of Shanghai First Maternity and Infant Hospital between January 2011 and December 2014. METHODS: HPV GenoArray test kit (HybriBio Ltd) was used to perform HPV genotyping and was also used in DNA amplification and HybriBio's proprietary flow-through hybridization technique. RESULTS: In this study, total patients analyzed were 4585. Among 4585 sample the HPV positive patients were 1460 i.e. 31.84% in total. On the basis of pathological report normal were 1358, with inflammation 2441, with low grade lesion were 399, high grade lesion were 353, CIN were 19 and cervical carcinoma were 15. Among normal HPV positive were 215 (15.8%), among inflammation HPV positive were 735 (30.11%). HPV positive in low grade lesion were 353 i.e. 59.77%. In high grade lesion 211 were HPV positive among 272 (68.17%). The percentage of HPV positive was 73.68% i.e. 14 out of 19 patient in cervical carcinoma in situ. 13 patient out of 15 i.e. 86.67% of Cervical carcinoma were HPV positive. Among all percentage of HPV positive was high among cervical carcinoma then cervical carcinoma in situ then high grade lesion in decreasing fashion to low grade lesion and in normal. Highest prevalence i.e. 22.67% is of HPV 52 subtype and HPV 16 has second highest prevalence with 17.67% among HPV positive cases. Sensitivity of TCT detection is 71.6%. Specificity of TCT detection is 79.6%. Sensitivity of HPV-DNA detection is 65.2%. Specificity of HPV-DNA detection is 78.2%. CONCLUSION: HPV is one of major health concern in shanghai having high prevalence rate in comparison to other part of china and other part of world. This has implications for the future cervical cancer burden and the priority to be given to prevent cervical cancer in Shanghai, especially, given the promising efficacy of prophylactic vaccines against HPV52, 16 and 58. This study also shows high sensitivity and specificity of TCT and HPV-DNA detection.

[Effect of intensive insulin therapy on the clinical results of postoperative patients with gastric cancer].

OBJECTIVE: To investigate the influence of intensive insulin therapy on the results of postoperative patients with gastric cancer. METHODS: Forty-six patients with gastric cancer underwent radical operation were randomly divided into two groups: intensive group (n=23, to control blood glucose at 4.4 to 6.1 mmol/L) and conventional group (n=23, to control blood glucose at 10.0 to 11.1 mmol/L). Fasting blood glucose( FBG), fasting insulin (FINS), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C reaction protein (CRP) in 46 patients were detected dynamically during perioperative period. Insulin resistance index (HOMA-IR) were calculated using Homeostasis Model Assessment (HOMA) to evaluate insulin sensitivity. Postoperative complications and other clinical data were recorded. RESULTS: No hypoglycemia occurred in the two groups. Compared with conventional group, morbidity and postoperative duration of fever, antibiotic use and the length of hospital stay in intensive group were significantly reduced (P < 0.05). On the day 1 and 3 after surgery, HOMA-IR and serum levels of TNF-alpha, IL-6 and CRP in patients of intensive group were significantly lower than those in conventional group (P < 0.05). CONCLUSIONS: Intensive insulin therapy could counteract the state of high-inflammation and then improve the outcome of postoperative patients.