Clinical Lymph Node Metastasis Research Articles

High expression of HSP60 and survivin predicts poor prognosis for oral squamous cell carcinoma patients

BackgroundHSP60 is a heat shock proteins (HSPs) family member and help mitochondrial protein to fold correctly. Survivin is one of the inhibitors of apoptosis protein family member, which plays a significant part in cancer progression. They were capable of forming HSP60-survivin complexes and involved in the development of various tumors.MethodsThe Cancer Genome Atlas (TCGA) database demonstrated that HSP60 and survivin and their correlation on mRNA expression level with OSCC patients. Besides, expression of HSP60 and survivin proteins was studied utilizing immunohistochemistry in tissue microarrays (TMA) in OSCC and in adjacent non-cancerous squamous epithelium (Non-CCSE) tissues.ResultsSignificantly increased levels of HSP60 and survivin in most cancers compared to normal tissue by pan-cancer analysis. HSP60 and survivin proved a significantly increased expression in OSCC samples compared to Non-CCSE both on mRNA and protein (both P < 0.05). Additionally, elevated HSP60 displayed a positive correlation with survivin in terms of mRNA and protein expression levels (all P < 0.001). Patients with OSCC who had advanced clinical stage or lymph node metastasis (LNM) showed higher HSP60 expression (P = 0.004, P = 0.006, respectively). Higher levels of the proteins HSP60 and survivin were significantly inversely correlated relationship with OSCC patients’ overall survival rates in multivariate survival analysis (P = 0.018, P = 0.040). From the above results, overexpression of HSP60 and survivin protein may serve as independent biomarkers predicting poor prognosis in OSCC.ConclusionsElevated HSP60 and survivin might be served as novel poor prognosis biomarkers for surgically resected OSCC patients.

Surgical strategy for patients with papillary thyroid carcinoma invading the trachea: a comparison of tracheal sleeve resection with end-to-end anastomosis and window resection with tracheocutaneous fistula.

Sleeve resection with end-to-end anastomosis (Procedure A) and window resection with a tracheocutaneous fistula (Procedure B) are the major surgical procedures for patients with papillary thyroid carcinoma (PTC) exhibiting transluminal tracheal invasion. For each procedure, the indications, postoperative course, and treatment results were examined retrospectively. Of 1,456 patients with PTC (maximum tumor diameter >1 cm) who received initial treatment between 1993 and 2013, we reviewed 51 patients. Of these 51 cases, 45 showed full-layer tracheal invasion, and 6 did not reach the tracheal mucosa, but required full-layer tracheal resection. Twenty-four patients underwent Procedure A, and 27 patients underwent Procedure B. Regarding surgical procedure selection, Procedure B was selected significantly more frequently than Procedure A for cases with preoperative recurrent laryngeal nerve (RLN) palsy, tumor invasion of the esophagus, clinical lymph node metastasis, or a large number of resected tracheal rings. Postoperative airway-related complications were not significantly different between the procedures, but decreased with the use of intraoperative neuromonitoring (IONM). The postoperative hospital stay was significantly longer for Procedure B than for Procedure A. In addition, the rate of a permanent postoperative tracheostoma was higher with Procedure B than with Procedure A. Local recurrence-free survival (LRFS) and cause-specific survival (CSS) did not differ significantly between the two procedures. Certain patients may benefit from Procedure A with IONM in terms of a shorter hospital stay and avoiding the need for a permanent tracheostoma. Although Procedure B was indicated for patients with more advanced disease than Procedure A, treatment outcomes were similar.

243. COMPARISON BETWEEN THE THERAPEUTIC AND PROPHYLACTIC LYMPHADENECTOMY OF THE SUPRACLAVICULAR AREA FOR PATIENTS WITH ESOPHAGEAL CANCER

Abstract Backgrounds Lymphadenectomy of the supraclavicular area (SCA) for patients with esophageal cancer has still remained controversial. Some previous studies showed that it could not improve survival. In this study, we retrospectively investigated the results of therapeutic and prophylactic lymphadenectomy around SCA for patient with esophageal cancer. Methods From 2010 to 2015, the patients who underwent esophagectomy with 3-fields lymphadenectomy were enrolled in this study. Patients with cervical esophageal cancer and with pN3 were excluded. Clinical nodal metastasis was decided on CT findings. Efficiency of index for lymphadenectomy (EI) was calculated with nodal incidence multiplied by 3-year relapse free survival (3yRFS). Results A total of 514 patients was enrolled in this study. Therapeutic lymphadenectomy was performed in 47 patients, and prophylactic lymphadenectomy was performed in 467 patients. In the therapeutic lymphadenectomy group, nodal metastasis was found in 17 patients (36.2%) and 3yRFS of these patients was 34.3%, and EI was 12.4. Meanwhile, in the prophylactic group, nodal metastasis was found in 14 (3.0%) and 3yRFS of these patients was 35.7%, and EI was 1.1. Of 514 patients, 138 received neo-adjuvant treatments. In the neo-adjuvant group, EI of the therapeutic lymphadenectomy was 21.5, and that of the prophylactic lymphadenectomy was 2.7. In the upfront surgery group, EI of the therapeutic lymphadenectomy was 0, and that of the prophylactic lymphadenectomy was 0.6. Conclusion The 3yRFS of the patients with pathological nodal metastasis in the SCA was relatively good. However, EI in the prophylactic group was very low due to very low incidence of the pathological nodal metastasis in the SCA. Clinical significance of prophylactic lymphadenectomy of SCA is not clear based on our data.

The effect of central lymph node dissection on the prognosis of cN0 papillary thyroid microcarcinoma: a mid-term follow-up study

BackgroundTo investigate the effect of central lymph node dissection on the prognosis of patients with papillary thyroid microcarcinoma (PTMC) without clinical lymph node metastasis (cN0).MethodsAccording to the inclusion and exclusion criteria, 462 patients with cN0 PTMC underwent surgery in the Second Department of General Surgery, Zhongshan City People’s Hospital from January 1, 2007, to June 31, 2017. They were divided into two groups: the undissection group (262 cases) and the dissection group (170 cases). A comparison was made between the two groups in terms of postoperative complications, recurrences, metastases, etc., as well aslymph node metastasis risk factors in the central region of cN0 PTMC.ResultsThere was no lymphatic leakage or death in all patients after the operation. In the dissection group, 64 cases (37.6%) of central lymph node metastasis were found after the postoperative pathological examination. The undissection group was followed up for (92 ± 28.7) months, and the dissection group was followed up for (86 ± 25.4) months (t=-2.165, P = 0.031). In the two groups, there were no lung metastases, bone metastases, or other distant metastases during the follow-up period. In the undissection group, there were 7 cases, while in the dissection group, there were just 2. Recurrence rates between the two groups did not differ significantly (χ2 = 0.126, P = 0.169); Similarly, disease-free survival curves did not differ significantly (χ2 = 2.565, P = 0.708). Hypoparathyroidism and Hypocalcemia also had no difference between the group. In comparison to the undissection group, the capsular invasion rate (P = 0.026), calcification rate(P < 0.001) incidence of postoperative hoarseness (P = 0.017), and hand and foot numbness rate (P < 0.001) were all considerably greater in the dissection group. Multivariate research revealed that capsular invasion (OR = 9.42, P = 0.002), multifocal (OR = 24.57, P < 0.001), and tumor diameter > 5 mm (OR = 5.46, P = 0.019) were the independent risk factors for central lymph node metastasis in cN0 PTMC.ConclusionsThyroidectomy alone is safe for cN0 PTMC, but longer-term follow-up is still required for changes in central lymph nodes. For cN0 PTMC patients with tumor diameter > 5 mm, multifocal, and capsular invasion, central lymph node metastasis is more likely to occur. Comprehensive evaluation and individualized and precise treatment are essential.

A multi-institutional retrospective study of 340 cases of sinonasal malignant tumor

ObjectiveSinonasal malignant tumors (SNMT) are relatively rare among head and neck malignant tumors. Most are squamous cell carcinomas, and malignant melanomas, olfactory neuroblastomas, adenoid cystic carcinomas, sarcomas, and others also occur. The most common primary site of nasal sinus squamous cell carcinoma is the maxillary sinus.In recent years, a decrease in incidence of maxillary sinus squamous cell carcinoma (MSSCC) has been reported along with a decrease in the incidence of sinusitis. MSSCC is treated with a combination of surgery, radiation, and chemotherapy. Treatment decisions are made according to the progression of the disease, the patient's general condition, and the patient's own wishes. There are variations in treatment policies among facilities due to the specialty of staff and cooperation with other departments at each facility. We conducted a multi-institutional retrospective study to compare outcomes by treatment strategy. MethodsIn this study, 340 patients with SNMT who were treated at 13 Hospitals (Head and Neck Oncology Group (Kyoto-HNOG) ) during the 12-year period from January 2006 to December 2017 were included. There were 220 patients with squamous cell carcinoma, 32 with malignant melanoma, 21 with olfactory neuroblastoma, and 67 with other malignancies. Of the squamous cell carcinomas, 164 were of maxillary sinus origin. One hundred and forty cases of MSSCC that were treated radically were included in the detailed statistical analysis. ResultsThere were 5 cases of cStage I, 9 cases of cStage II, 36 cases of cStage III, 74 cases of cStage IVa, and 16 cases of cStage IVb. There were 92 cases without clinical lymph node metastasis (cN(-)) and 48 cases with clinical lymph node metastasis(cN(+)).Primary tumors were treated mainly by surgery in 85 cases (Surg) and by radical radiation therapy (with or without chemotherapy) of 6-70 Gy in 55 cases(non-Surg).The 5-year overall/disease-free survival rate (OS/DFS) for MSSCC was 65.1%/51.6%. Old age, renal dysfunction, and clinical T progression were independent risk factors for OS, and renal dysfunction was an independent risk factor for DFS.In cN(-) patients, OS and DFS were significantly better in Surg group than in non-Surg group. In cN(+) patients, there was no significant difference in OS and DFS between Surg and non-Surg groups. ConclusionFor patients with MSSCC without lymph node metastasis, aggressive surgery on the primary tumor contributes to improved prognosis.

Potential Role for Observation in Small Solid Pseudopapillary Neoplasm (SPN).

Solid pseudopapillaryneoplasms(SPN)arerare tumorsof the pancreas, typically affecting young women.Resection is the mainstay of treatment but is associated with significant morbidity and potential mortality. Weexplore the ideathat small, localized SPN could be safely observed. This retrospective review of the Pancreas National Cancer Database from 2004 to 2018 identified SPN via histology code8452. A total of 994 SPNs were identified. Mean age was 36.8 ± 0.5 years, 84.9% (n = 844) were female, and most had a Charlson-Deyo Comorbidity Coefficient (CDCC) of 0-1 (96.6%, n = 960). Patients were most often staged clinically as cT2 (69.5%, n = 457) followed by cT3 (17.6%, n = 116), cT1 (11.2%, n = 74), and cT4 (1.7%, n = 11). Clinical lymph node and distant metastasis rates were 3.0 and 4.0%, respectively. Surgical resection was performed in 96.6% of patients (n = 960), most commonly partial pancreatectomy (44.3%) followed by pancreatoduodenectomy (31.3%) and total pancreatectomy (8.1%). In patients clinically staged as node (N0) and distant metastasis (M0) negative, occult pathologic lymph node involvement was found in 0% (n = 28) of patients with stage cT1 and 0.5% (n = 185) of patients with cT2 disease. The risk of occult nodal metastasis significantly increased to 8.9% (n = 61) for patients with cT3 disease. The risk further increased to 50% (n = 2) in patients with cT4 disease. Herein, the specificity of excluding nodal involvement clinically is 99.5% in tumors ≤ 4 cm and 100% in tumors ≤ 2 cm. Therefore, there may be a role for close observation in patients with cT1N0 lesions to mitigate morbidity from major pancreatic resection.

Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism

Myc is a well-known proto-oncogene that is frequently amplified and activated in breast cancer, especially in triple-negative breast cancer (TNBC). However, the role of circular RNA (circRNA) generated by Myc remains unclear. Herein, we found that circMyc (hsa_circ_0085533) was remarkably upregulated in TNBC tissues and cell lines, which was attributed to gene amplification. Genetic knockdown of circMyc mediated by lentiviral vector significantly inhibited TNBC cell proliferation and invasion. Importantly, circMyc increased cellular triglycerides, cholesterols and lipid droplet contents. CircMyc was detected in both cytoplasm and nucleus, cytoplasmic circMyc could directly bind to HuR protein, facilitating the binding of HuR to SREBP1 mRNA, resulting in increasing SREBP1 mRNA stability. Nuclear circMyc bound to Myc protein, facilitating the occupation of Myc on SREBP1 promoter, leading to increasing SREBP1 transcription. As a result, the elevated SREBP1 increased the expression of its downstream lipogenic enzymes, enhancing lipogenesis and TNBC progression. Moreover, the orthotopic xenograft model showed that depletion of circMyc markedly inhibited lipogenesis and reduced tumor size. Clinically, high circMyc was closely related to larger tumor volume, later clinical stage and lymph node metastasis, functioning as an adverse prognostic factor. Collectively, our findings characterize a novel Myc-derived circRNA controlling TNBC tumorigenesis via regulation of metabolic reprogramming, implying a promising therapeutic target.

Profile of BRAFV600E, BRAFK601E, NRAS, HRAS, and KRAS Mutational Status, and Clinicopathological Characteristics of Papillary Thyroid Carcinoma in Indonesian National Referral Hospital.

BRAFV600E and RAS mutations are the most common gene mutations in papillary thyroid carcinoma (PTC) that may be correlated with its biological behavior. There are still limited data about BRAFV600E and RAS mutations in Indonesia. This study aims to determine the prevalence of BRAFV600E and RAS mutations, and their association with clinicopathologic characteristics. Patients who had total thyroidectomy from 2019 to 2021 and those who met our study criteria underwent PCR and DNA sequencing analysis for BRAFV600E, BRAFK601E, exon 2 and 3 of NRAS, HRAS, and KRAS. Analyses were performed to determine the associations of BRAFV600E and RAS mutations with clinicopathologic characteristics. Of 172 PTC patients, BRAFV600E mutation was observed in 37.8% of the patients and RAS mutations were found in 21.5%. One patient harbored BRAFK601E mutation. There was a significant association of BRAFV600E with a high-stage (p = 0.033, OR: 3.279; 95% CI: 1.048-10.259), tall-cell variants (p ≤0.001, OR: 41.143; 95% CI: 11.979-141.308), non-encapsulated (p = 0.001, OR: 4.176; 95% CI: 2.008-8.685), lymphovascular invasion (p = 0.043, OR: 1.912; 95% CI: 1.018-3.592), extrathyroidal extension (p = <0.001, OR: 3.983; 95% CI: 1.970-8.054), and lymph node metastasis (p = 0.009, OR: 2.301; 95% CI: 1.224-4.326). Follicular variant (p = 0.001, OR: 7.011; 95% CI: 2.690-18.268), encapsulated (p = 0.017, OR: 2.433; 95% CI: 1.161-5.100), and absent of extrathyroidal extension (p = 0.033, OR: 2.890; 95% CI: 1.052-7.940) were associated with RAS mutations. A significant association between BRAFV600E mutation and high clinical stage, tall-cell variants, non-encapsulated morphology, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis in PTC was observed. RAS mutations were associated with the follicular variant, encapsulated tumor, and no extrathyroidal extension. HRAS-mutated PTC frequently exhibited tumor multifocality.

Prediction of Lymph Node Metastasis of Mixed Ground-glass Nodules Based on Clinical Imaging Information

Previous studies have shown that lymph node metastasis only occurs in some mixed ground-glass nodules (mGGNs) which the pathological results were invasive adenocarcinoma (IAC). However, the presence of lymph node metastasis leads to the upgrading of tumor-node-metastasis (TNM) stage and worse prognosis of the patients, so it is important to perform the necessary evaluation before surgery to guide the operation method of lymph node. The aim of this study was to find suitable clinical and radiological indicators to distinguish whether mGGNs with pathology as IAC is accompanied by lymph node metastasis, and to construct a prediction model for lymph node metastasis. From January 2014 to October 2019, the patients with resected IAC appearing as mGGNs in computed tomography (CT) scan were reviewed. All the lesions were divided into two groups (with lymph node metastasis or not) according to their lymph node status. Lasso regression model analysis by applying R software was used to evaluate the relationship between clinical and radiological parameters and lymph node metastasis of mGGNs. A total of 883 mGGNs patients were enroled in this study, among which, 12 (1.36%) showed lymph node metastasis. Lasso regression model analysis of clinical imaging information in mGGNs with lymph node metastasis showed that previous history of malignancy, mean density, mean density of solid components, burr sign and percentage of solid components were informative. Prediction model for lymph node metastasis in mGGNs was developed based on the results of Lasso regression model with area under curve=0.899. Clinical information combined with CT imaging information can predict lymph node metastasis in mGGNs.

CDK5RAP2 is a Wnt target gene and promotes stemness and progression of oral squamous cell carcinoma

In oral squamous cell carcinoma (OSCC), a highly aggressive and frequently lethal malignancy, the role and action mechanism of the microtubule regulatory protein CDK5RAP2 have not been fully understood. Here, we show that CDK5RAP2 is highly expressed in OSCC and its expression correlates with clinical stage and lymph node metastasis of the disease. The expression of CDK5RAP2 is regulated by the Wnt signaling pathway. Depletion of CDK5RAP2 inhibits the tumorigenesis and migration of OSCC cells and alters the OSCC cancer stem (-like) cell (CSC) signature. Notably, suppression of CDK5RAP2 expression disrupts spindle orientation during mitosis. Collectively, these results identify CDK5RAP2 as a potential CSC marker and reveal a mechanism that controls the CSC population in OSCC.

Evaluating surgical treatment options for small nonfunctional pancreatic neuroendocrine tumors in the NCDB.

645 Background: The role of surgery for small (≤2 cm), nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) remains controversial due to the wide range of tumor aggressiveness. Consensus guidelines of the US, Europe, and Japan offer different recommendations for treatment of small NF-PNETs. The objective of this study is to evaluate the survival benefit of surgical resection for small NF-PNETs. Methods: Patients with NF-PNETs were identified in the National Cancer Database from 2004 to 2018. Small NF-PNETs were divided into two groups: group 1a (tumor ≤1 cm) and group 1b (tumor 1.1 – 2.0 cm). Cox regression models were used to compare the overall survival between resected and unresected small NF-PNETs patients. Interactions between preoperative factors and surgery were estimated using subgroup analyses. Results: We identified 1,278 patients in group 1a and 3,363 patients in group 1b. After adjusting for preoperative factors, surgery was associated with longer survival for patients in group 1b (HR, 0.58; 95% CI, 0.42–0.80; P &lt;0.001), but not for patients in group 1a (HR, 0.68; 95% CI, 0.41–1.11; P = 0.122). Interaction analysis found that age younger than 65 years, fewer comorbidities, treatment at academic institutions, distal pancreatic tumors, and clinical lymph node metastasis were factors associated with longer survival in group 1b by surgery. Conclusions: Findings from this large study support surgical resection for some patients with NF-PNETs (1.1 – 2.0 cm). This, of course, must be taken in context with the patient’s clinical situation. Based on data available for analysis in this study, resection for subcentimeter NF-PNETs does not appear to be of general benefit, but should also be investigated in the context of Ki-67 index.[Table: see text]

Abnormal expressions of PURPL, miR-363-3p and ADAM10 predicted poor prognosis for patients with ovarian serous cystadenocarcinoma.

Objective: This study aimed to elucidate the prognostic implications of deviant expressions of long non-coding RNA (lncRNA) p53 upregulated regulator of p53 levels (PURPL), microRNA-363-3p (miR-363-3p), and ADAM metallopeptidase domain 10 (ADAM10) in patients diagnosed with ovarian serous cystadenocarcinoma (OSC). Methods: To predict and refine the targeted miRNAs and downstream target genes for PURPL, we utilized open medical databases. Through the employment of real-time RT-PCR, we conducted tissue analysis to discern the expressions of PURPL, miR-363-3p, and ADAM10 in both OSC and control tissues. The pathological correlations in the clinic and the prognostic implications of deviant expressions of PURPL, miR-363-3p, and ADAM10 in OSC patients were analyzed independently. Results: Database inquiries revealed that PURPL might target miR-363-3p, and in turn, miR-363-3p could target ADAM10. Differential expression of PURPL, miR-363-3p, and ADAM10 was observed between OSC and paired tissues. The premature version of miR-363-3p, miR-363, correlated with overall survival (OS), while ADAM10 corresponded with progression-free survival (PFS) in ovarian cancer patients. Tissue detection displayed significantly elevated expressions of PURPL and ADAM10, and conspicuously diminished expressions of miR-363-3p in OSC tissues compared to the control tissues (P<0.05). A negative correlation was observed between the expressions of PURPL and miR-363-3p, and miR-363-3p and ADAM10, while a positive correlation was found between PURPL and ADAM10 in different ovarian tissues (P<0.05). In OSC tissues, upregulation of PURPL was associated with an advanced clinical stage, TP53 mutation, and lymph node metastasis (P<0.05), downregulation of miR-363-3p was associated with a more advanced clinical stage and lymph node metastasis (P<0.05), and overexpression of ADAM10 correlated with a more advanced FIGO stage. High expressions of PURPL and ADAM10, and low expression of miR-363-3p, were linked with poor PFS and OS in OSC patients, respectively (P<0.05). In addition, OSC patients with elevated PURPL and reduced miR-363-3p, patients with elevated PURPL and ADAM10, and patients with reduced miR-363-3p and elevated ADAM10 also demonstrated worse PFS and OS, respectively (P<0.05). Conclusions: The anomalous expressions of PURPL, miR-363-3p, and ADAM10 might contribute to the pathogenesis of OSC via up-down stream regulation, and these abnormal expressions could serve as potential prognostic indicators for OSC patients.

Real-life utility of five-gene panel test in preoperative thyroid fine-needle aspiration biopsy: a large cohort of 740 patients study.

Fine-needle aspiration (FNA) biopsy is an effective method to discriminate malignant thyroid nodules but reaches indeterminate results in approximately 30% of cases. Molecular testing can improve the diagnostic accuracy of FNA. This study aimed to investigate the real-life utility of the five-gene panel testing in thyroid FNAs. 759 thyroid nodules from 740 patients under FNAs were retrospectively enrolled. Gene mutation information and clinical parameters, including age, gender, tumor size, and lymph node metastasis, were respectively recorded. Cytological results were classified based on The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We analyzed mutational hotspots in BRAF, KRAS, NRAS, HRAS, and TERT genes from FNA specimens. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated to assess diagnostic performance. We identified 549 five-gene mutations in 759 nodules (72.3%), and the mutation frequency increased from the lower TBSRTC category to the upper category. BRAF.p.V600E showed the highest mutation incidence (71.3%) in the five-gene panel, correlated with the small to medium diameter (p = 0.008, p = 0.012) and high cytological categories (p < 0.001). The sensitivity, specificity, PPV, NPV, and accuracy of the combination of FNA cytology and five-gene detection were 96.83%, 100%, 100%, 42.86%, and 96.90%, respectively. The mutation frequency of the five-gene panel is 72.3% in thyroid FNAs. BRAF.p.V600E has the highest alteration rate, which is closely associated with tumor size and cytological results. The five-gene panel can improve the sensitivity and accuracy of FNA cytology, which may represent a valid adjunct technique in distinguishing thyroid nodules.

Pathological multifocality is not a prognosis factor of papillary thyroid carcinoma: a single-center, retrospective study

IntroductionNon-total thyroidectomy (non-TTx) is a widely accepted operative procedure for low-risk papillary thyroid carcinoma (PTC). PTC patients preoperatively diagnosed with unifocal disease are often revealed as having multifocal foci by microscopy. The present study determined whether or not patients with clinically unifocal, but pathologically multifocal non-high-risk PTC treated with non-TTx have an increased risk of a poor prognosis compared to those with pathologically unifocal PTC.Materials and methodsPTC patients diagnosed as unifocal preoperatively who underwent non-TTx were multifocal in 61 and unifocal in 266 patients microscopically. Oncologic event rates were compared between pathologically multifocal and unifocal PTC patients.ResultsPathological multifocality was associated with positive clinical lymph node metastasis (cN1) (odds ratio [OR] 4.01, 95% confidence interval [CI]: 1.91–8.04) and positive pathological lymph node metastasis (pN1) in > 5 nodes (OR 3.68, 95% CI: 1.60–8.49). No patients died from PTC. There was no significant difference in the disease-free survival rate, remnant thyroid disease-free survival rate, lymph node disease-free survival rate, or distant disease-free survival rate between the two groups. Recurrence in pathologically multifocal PTC patients was locoregional in all cases and able to be salvaged by reoperation. Cox proportional hazard model analyses showed no significant difference in recurrence rates with regard to pathological multifocality and cN or number of pNs.ConclusionThe prognosis of PTC with pathological multifocality treated by non-TTx was not inferior to that of unifocal PTC. Immediate completion thyroidectomy is not necessary when microscopic foci are proven.

Cytoreductive Surgery in Patients with Urothelial Bladder Cancer

Cytoreductive cystectomy appears to have survival advantages as a part of multimodal approach for well-selected patients with bladder cancer. Patient with clinical lymph node metastases might benefit from surgical consolidation after achieving a measurable response to chemotherapy. The exact role of cytoreductive/consolidative cystectomy is yet to be determined in well-designed prospective trials.

Transcription factor ZNF488 accelerates cervical cancer progression through regulating the MEK/ERK signaling pathway.

Cervical cancer (CC) is one of the most common gynecological malignancies worldwide. Zinc Finger Protein 488 (ZNF488) has been identified as an oncogene in nasopharyngeal carcinoma. However, its biological role and potential mechanism in CC remain to be elucidated. In the present study, upregulation of ZNF488 expression in human CC tissues was found in clinical samples and analyzed in The Cancer Genome Atlas (TCGA) dataset, which was associated with clinical staging and lymph node metastasis. Quantitative real time polymerase chain reaction (PCR) and western blot assays indicated that the expression of ZNF488 was up-regulated in CC cells. Cell colony formation and cell cycle analysis assays suggested that ZNF488 promoted CC cell proliferation and cycle progression. Knockdown of ZNF488 inhibited tumor growth of xenograft tumor mice in vivo, in agreement with the levels of ZNF488 and Ki-67. Moreover, transwell and western assays demonstrated that ZNF488 enhanced CC cell migration and invasion. Additionally, knockdown of ZNF488 also inhibited lung metastasis of CC cells in vivo. Further mechanism analysis implied that ZNF488 promoted the MEK/ERK signaling pathway. ERK inhibitor PD98059 significantly weakened the proliferation and epithelial-mesenchymal transformation (EMT) promotion effect of ZNF488. Collectively, ZNF488 exerts its oncogene function partially through modulating MEK/ERK signaling pathway in CC, indicating that ZNF488 may provide a promising therapeutic target for the treatment of CC.

Calibrated Regression Models Based on the Risk of Clinical Nodal Metastasis Should be Used as Decision Aids for Prostate Cancer Staging to Reduce Unnecessary Imaging.

Radionuclide imaging will change the role of computed tomography and magnetic resonance imaging (CT/MRI) for prostate cancer (CaP) staging. Current guidelines recommend abdominopelvic imaging for new cases of CaP categorized as unfavorable intermediate risk (UIR) or higher. We assessed the performance characteristics of CT/MRI based on the National Comprehensive Cancer Network (NCCN) guidelines and developed a model that predicts cN1 disease using conventional imaging. We selected patients in the National Cancer Database diagnosed with CaP from 2010 to 2016 with available age, prostate specific antigen, clinical locoregional staging, biopsy Gleason grading, and core information. Multivariate logistic regression (MLR) was used on a undersampled training dataset using cN1 as the outcome. Performance characteristics were compared to those of the three most recent versions of the NCCN guidelines. A total of 443,640 men were included, and 2.5% had cN1 disease. Using CT/MRI only, the current NCCN guidelines have a sensitivity of 99%, and the number needed to image (NNI) is 24. At the same sensitivity, the cN1 risk was 1.6% using the MLR. The NNI for UIR alone is 341. Using the MLR model and a threshold of 10%, the PPV is 10.3% and 64% of CTs/MRIs could be saved at a cost of missing 6% of cN1 patients (or 0.15% of all patients). The NCCN guidelines are sensitive for detecting cN1 with CT/MRI, however, the number needed to image is 24. Obtaining CT/MRI for nodal staging when patients have a cN1 risk of 10% would reduce total imaging while still remaining sensitive. As novel PET tracers becomes increasingly used for initial CaP staging, well calibrated prediction models trained on the outcome of interest should be developed as decision aids for obtaining imaging.

Mesorectal excision with or without lateral lymph node dissection for elderly patients with mid-low rectal cancer: safety and feasibility analysis.

The perioperative safety and survival benefits of lateral lymph node dissection in elderly patients have been less reported. This study aimed to compare short-term and survival outcomes of total mesorectal excision and total mesorectal excision+lateral lymph node dissection in elderly patients. A total of 444 elderly patients (≥65 years) with middle-low rectal cancer were enrolled in three institutions and divided into the total mesorectal excision+lateral lymph node dissection group (n=110) and the total mesorectal excision group (n=334). Eighty-three matched pairs were selected for evaluation after propensity matching. Data of 297 patients (age <65 years) with middle-low rectal cancer who underwent total mesorectal excision+lateral lymph node dissection were also collected and reviewed. Clinical and pathological features, postoperative outcomes and survival data were collected and analyzed. Compared with the total mesorectal excision group, the operation time of patients in the total mesorectal excision+lateral lymph node dissection group was significantly longer (277.6 vs. 171.4 min, P<0.001), and the estimated blood loss was significantly more (119.6 vs. 57.5ml, P=0.014). Although there was no significant difference in overall complications (24.1% vs. 14.4%, P=0.115) and grade 3-5 complications (9.6% vs. 7.2%, P = 0.576) between the two groups, the incidence of urinary retention (10.8% vs. 2.4%, P = 0.029) was higher in the total mesorectal excision+lateral lymph node dissection group. Two groups of patients achieve a similar 3-year overall survival (92.8% vs. 85.4%, P = 0.195) and 3-year disease-free survival (81.5% vs. 73.0%, P=0.625). In addition, we compared long-term outcomes in 110 elderly patients with total mesorectal excision+lateral lymph node dissection and 297 non-elderly patients with total mesorectal excision+lateral lymph node dissection, and the results showed that 3-year (89.2% vs. 80.9%, P=0.546) and disease-free survival (76.4% vs. 70.4%, P=0.346) were similar between elderly and non-elderly patients. Although urinary retention is closely related to the implementation of lateral lymph node dissection in elderly patients, total mesorectal excision with lateral lymph node dissection could be performed safely with accepted overall and grade 3-5 postoperative complications in elderly patients with rectal cancer. Moreover, elderly patients with clinical lateral lymph node metastasis can also benefit from lateral lymph node dissection as well as younger patients. Prospective studies with large sample sizes are needed to verify our results further.

Screening and validation of lymph node metastasis risk-factor genes in papillary thyroid carcinoma.

Although most papillary thyroid carcinoma (PTC) cases have a good prognosis, some PTCs are more aggressive and are often accompanied by lymph node (LN) metastasis, a high recurrence rate, and poor prognosis. Distinguishing highly invasive metastatic PTC is an urgent problem that needs to be addressed clinically. We analyzed a microarray of metastasized PTC and validated it using quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry to identify biomarkers that can be used to assess the risk of PTC metastasis. The microarray of metastasized PTC was screened using the Gene Expression Omnibus (GEO) database. The differences between cancer and normal tissues were analyzed using the official GEO tool: GEO2R. Gene expression profile data (GEPIA) were used to verify the expression of differential genes in large samples and to analyze their correlation. The Kaplan-Meier plotter (KM-plotter) database was used for the analysis of genes potentially related to survival. RT-qPCR was used to check the expression of risk factor genes in pathological sections from PTC patients with clinical LN metastasis. Immunohistochemistry was used to verify the expression of core risk-associated genes. Fourteen PTC metastasis-associated genes were identified. In metastasized PTC, CLDN1, LRP4, LRRK2, and TENM1 were highly expressed, whereas DIO1, DPP6, HGD, IPCEF1, MT1F, SLC26A4, SLC26A7, SPX, TFF3, and TPO were expressed at low levels, compared to expression in normal tissues. DIO1, HGD, SLC26A4, and TPO were found to be the core risk genes in the PTC metastatic risk set. Results based on clinical samples showed that the expression differences for metastasis risk-associated genes were consistent with the bioinformatics analysis results. Fourteen differentially expressed genes (CLDN1, LRP4, LRRK2, TENM1, DIO1, DPP6, HGD, IPCEF1, MT1F, SLC26A4, SLC26A7, SPX, TFF3, TPO) are associated with an increased risk of PTC metastasis, and DIO1, HGD, SLC26A4, and TPO are the key risk-associated genes in this set that might affect the occurrence and development of PTC through iodine metabolism. These genes could provide a reference for clinical metastatic PTC risk evaluation and treatment.

340. PROGNOSIS OF DIFFUSELY INFILTRATIVE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Diffusely infiltrative esophageal squamous cell carcinoma is so rare that very few studies have been reported. Therefore, it has not been clear whether the survival of patients with this disease is poor or not. In this study, we retrospectively investigated our long-term results of radical esophagectomy for patients with diffusely infiltrative esophageal squamous cell carcinoma in our institution. In addition, we tried to detect prognostic factors of this disease if possible. Data were retrospectively collected from medical records. Eligible patients underwent esophagectomy for esophageal squamous cell carcinoma with diffuse infiltration from 2002 to 2018 in our institution. Diagnosis of this disease was done in the conference of esophageal surgical team based on the findings of endoscopy and upper gastrointestinal series. Overall survival rates were calculated by the Kaplan–Meier method, and statistical significance was determined by the log-rank. P value of&amp;lt;0.05 was considered statistically significant. 32 patients were selected in this study. Median age was 66 years old, cStage I/II/III/IV was 0/10/14/8 patients respectively, preoperative treatment was undergone for 11 patients. 5-year overall survival (OS) rate was 27.3% and 3-year OS rate was 37.5%. 5-year OS rate for each cStage II/III/IV was 48.0%, 14.3% 25.0%. Patients who underwent preoperative treatment seemed to have poor prognosis with statistically significant difference. Patients with clinical or pathlogical supraclavicular lymph node metastasis tended to have poor prognosis. In this study, about 20% patients could obtain long-term survival. Therefore, surgical intervention could be one of the treatments for the patient with this disease. And also, we may take into account the postoperative treatment for the patient with poor prognostic factor.