Redox proteomics of PANC-1 cells reveals the significance of HIF-1 signaling protein oxidation in pancreatic ductal adenocarcinoma pathogenesis.

BACKGROUND: Protein cysteine oxidation is substantially involved in various biological and pathogenic processes, but its implications in pancreatic cancer development remains poorly understood. METHODS AND RESULTS: In this study, we performed a global characterization of protein oxidation targets in PDAC cells through iodoTMT-based quantitative proteomics, which identified over 4300 oxidized cysteine sites in more than 2100 proteins in HPDE6c7 and PANC-1 cells. Among them, 1715 cysteine residues were shown to be differentially oxidized between HPDE6c7 and PANC-1 cells. Also, charged amino acids including aspartate, glutamate and lysine were significantly overrepresented in flanking sequences of oxidized cysteines. Differentially oxidized proteins in PANC-1 cells were enriched in multiple cancer-related biological processes and signaling pathways. Specifically, the HIF-1 signaling proteins exhibited significant oxidation alterations in PANC-1 cells, and the reduced PHD2 oxidation in human PDAC tissues was correlated with lower survival time in pancreatic cancer patients. CONCLUSION: These investigations provided new insights into protein oxidation-regulated signaling and biological processes during PDAC pathogenesis, which might be further explored for pancreatic cancer diagnosis and treatment.

Prediction of level V metastases in papillary thyroid microcarcinoma: a single center analysis.

BACKGROUND: The rate of level V metastases is significantly low and the necessity of routine level V dissection for papillary thyroid microcarcinoma (PTMC) with clinically lateral lymph node metastasis (LNM) is still controversial. METHODS: This study enrolled 114 consecutive PTMC patients with clinically suspected lateral LNM (N1b) who underwent modified radical neck dissection (levels II to V) at Xiangya Hospital of Central South University from September 2016 to July 2019. Univariate and multivariate analyses were performed to investigate the predictive factors of level V metastasis. The area under the receiver operating characteristic (ROC) curve (AUC), accuracy, specificity and sensitivity were used to determine the predictive value. RESULTS: The overall and occult rate of level V metastasis were 29.82% (34/114) and 7.02% (8/114), respectively. Univariate analysis showed that level V metastasis was significantly associated with gross extrathyroidal extension (ETE), level IV metastasis and 2-level simultaneous metastasis (all P<0.05). Gross ETE (OR =11.916, 95% CI, 1.404-102.19; P=0.023) and level IV metastasis (OR =8.497, 95% CI, 2.119-34.065; P =0.03) served as independent predictors of level V metastasis in N1b PTMC patients. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of gross ETE and level IV metastasis in predicting the level V metastasis were 25.3% vs. 82.4%, 97.5% vs. 73.8%, 82.69% vs. 76.32%, 80% vs. 57.04% and 75% vs. 90.77%, respectively. The AUC of gross ETE was lower than level IV metastasis (0.605 vs. 0.781, P=0.041). CONCLUSIONS: Routine level V dissection is necessary in N1b PTMC patients with level IV metastasis or gross ETE. Compared with gross ETE, level IV metastasis is superior in predicting level V metastasis.

Comparison of NOSES and Conventional Laparoscopic Surgery in Colorectal Cancer: Bacteriological and Oncological Concerns.

Background: Colorectal natural orifice specimen extraction surgery (NOSES) is considered to be a scarless operation that avoids the laparotomy of extraction specimen, but bacteriological and oncological concerns are raised with this technique. Objective: The purpose of this study was to compare the oncological and bacteriological outcomes of NOSES and conventional laparoscopic (CL) procedures. Methods: This is a retrospective study of prospectively collected outcomes data. Patients operated with colorectal cancer from January 2016 to December 2019 in Xiangya Hospital were assigned to the group NOSES and the group CL according to the size of the tumor. Prior to dissection, peritoneal lavage fluid was collected for cytological assessment. At the end of the procedure, peritoneal lavage fluid was collected for aerobic culture and cytological assessment. Baseline characteristics and short-term and long-term outcomes for NOSES and CL were compared. Results: Between January 2016 and December 2019, 212 patients were enrolled from our center and 185 patients were analyzed (96 and 89 in NOSES and CL groups, respectively). The bacterial positive rate of peritoneal lavage fluid was 34.4 vs. 32.6% in NOSES and CL groups, respectively (P = 0.80). The positive rate of tumor cells in peritoneal lavage fluid was 7.3 vs. 9.0% in NOSES and CL groups, respectively (P = 0.67). Univariate analysis showed that the positive rate of tumor cells in peritoneal lavage fluid was significantly associated with tumor invasion depth and lymph node metastasis (P < 0.05). T4 (OR = 20.47, 95%CI = 1.241-337.661; P = 0.04), N1 (OR = 5.445, 95%CI = 1.412-20.991; P = 0.01), and N2 (OR = 6.315, 95%CI = 1.458-27.348; P = 0.01) served as independent predictors of peritoneal lavage fluid positive oncology patients. Local recurrence-free survival was not significantly different between two groups (HR = 0.909, 95%CI = 0.291-2.840; P = 0.87). Conclusions: Compared with conventional laparoscopic procedure, NOSES is in conformity with the principle of asepsis and tumor-free technique and can be worthy of clinical application and promotion.

A nomogram to predict skip metastasis in papillary thyroid cancer.

BACKGROUND: Skip metastases are defined as lateral lymph node metastasis (LNM) without the involvement of central LNM in papillary thyroid cancer (PTC), and it is difficult to predict in clinical practice. Our study aimed to investigate the risk factors of skip metastasis and establish a nomogram for predicting the probability of skip metastasis in PTC patients. PATIENTS AND METHODS: A total of 378 consecutive PTC patients with clinically suspected LNM who underwent modified radical neck dissection (MRND) from March 2018 to July 2019 in our hospital were enrolled. Univariate and multivariate analyses were used to examine risk factors of skip metastasis, and a nomogram prediction model was established and internally validated. RESULTS: The incidence of skip metastases was 11.6% (44/378). Primary tumor size of ≤ 1 cm (OR = 2.703; 95% CI, 1.342-5.464; P = 0.005), age (OR = 1.051; 95% CI, 1.017-1.805; P = 0.005), and primary tumor location in the upper portion (OR = 6.799; 95% CI, 2.710-17.060; P < 0.001) were found to be independent risk factors for skip metastasis in PTC patients. A nomogram based upon these predictors performed well. The area under the curve (AUC) was 0.806 (95% CI, 0.736-0.876), and the P value of the Hosmer-Lemeshow goodness of fit test was 0.66. Decision curve analysis revealed that the nomogram was clinically useful. CONCLUSION: Based on the risk factors of skip metastasis, a high-performance nomogram was established, which can provide an individual risk assessment and can guide treatment decisions for patients.

Transcolonic natural orifice specimen extraction for laparoscopic radical right hemicolectomy on ascending colon cancer: one case report and literature review.

This paper first reports the technical procedures by using colonoscope for transluminal specimen extraction after totally laparoscopic radical right hemicolectomy. The patient described herein was diagnosed with ascending colon cancer and underwent transcolonic natural orifice specimen extraction via colonoscope assistance without abdominal wall assisted incisions at Xiangya Hospital of Central South University in June 2019. The duration of surgery was 246 minutes, and the intraoperative blood loss was 20 mL. The specimen was removed through the left half of the transverse colon, splenic flexure of colon, descending colon, sigmoid colon, rectum and anus while preserving the tumor integrity. The patient recovered very well without any complications. After 6 months of follow-up, the patient was well healed, the anal exhaust and defecation functions of the patient were normal, and there was no pain reported in relation to the smaller abdominal trocar incisions. The aim of this study is to demonstrate that transcolonic natural orifice specimen extraction surgery (transcolonic NOSES) for laparoscopic radical right hemicolectomy on ascending colon cancer is feasible and this approach can achieve satisfactory clinical outcomes.

Magnesemia: an independent risk factor of hypocalcemia after thyroidectomy.

BACKGROUND: This study was designed to investigate the impact of serum magnesium (Mg) levels on hypocalcemia after thyroidectomy. PATIENTS AND METHODS: In total, 242 patients with differentiated thyroid cancer were retrospectively analyzed. RESULTS: Multivariate regression analysis showed hypomagnesemia was an independent risk factor for hypocalcemia (P<0.001). While Mg in low levels (0.66 mmol/L ≤ Po-Mg ≤0.74 mmol/L) increased the risk of hypocalcemia, postoperative serum Ca (Po-Ca) levels were significantly lower in patients with hypomagnesemia than in patients with normomagnesemia (P=0.01), and the former patients suffered significant decreases in serum Ca (P=0.02). Compared to patients with a mild decline of serum Mg after surgery (ΔMg <0.17), serum Ca decline significantly increased (P<0.001) in patients with a severe decline of serum Mg (ΔMg ≥0.17), while the change in amounts of parathyroid hormone (PTH) after surgery was similar between the two groups (P>0.05). In patients with normal Po-Ca levels, hypomagnesemia increased the risk of symptoms related to hypocalcemia by 4.478 times (OR =5.478, 95% CI 1.724-17.403). CONCLUSION: Hypomagnesemia, or even a low serum Mg level within the normal range, can increase the risk of hypocalcemia. After excluding the potential effects of PTH on serum magnesium and calcium, serum Mg reduction is one of the most important factors that influences postoperative serum Ca reduction. What's more, hypomagnesemia is closely linked with symptoms.

Treatment optimization and prognostic considerations for primary squamous cell carcinoma of the thyroid.

BACKGROUND: Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare aggressive malignancy that usually presents in an advanced stage and has a poor prognosis. Our study aimed to investigate the clinical characteristics, treatment, and prognosis of PSCCT. METHODS: We retrospectively reviewed the medical information of patients with PSCCT diagnosed from January 2006 to May 2018 at Xiangya Hospital. Survival analysis was conducted using the Kaplan-Meier method, and Log-Rank tests were performed for statistical testing. RESULTS: We identified 12 patients with PSCCT (nine males and three females), accounting for only 0.19% of all thyroid cancer diagnosed during this time period. The median age of these patients was 59.5 years old and their symptoms included neck masses (n=5), hoarseness (n=2), dyspnea (n=1), dysphagia (n=1) and neck pain (n=1). Four patients were in stage IVA, five were stage IVB, and three patients were stage IVC. Six patients underwent comprehensive treatment (surgery + radiotherapy or surgery + radiotherapy + chemotherapy) and the remaining patients received radiotherapy and/or chemotherapy. The 6-month survival rate was 66.7%, compared to a 1-year survival rate of 25.0%, with a median overall survival time was 10.5 months. Kaplan-Meier analysis showed that the comprehensive treatment was superior to radiotherapy and/or chemotherapy (P=0.003). CONCLUSIONS: PSCCT is a rare type of thyroid cancer that is highly invasive and has a poor prognosis. We show that a comprehensive treatment plan can significantly improve patient survival.