Risk Factor For Disease-free Survival Research Articles

Monitoring expiratory carbon monoxide to study the effect of complete smoking cessation on definitive radiation therapy for early stage glottic carcinoma

Background Previous studies reported that cigarette smoking during radiation therapy was associated with unfavorable outcomes in various cancers using medical interviewing or monitoring of cotinine. Here, we evaluated the effect of smoking cessation on definitive radiation therapy for early stage glottic carcinoma by monitoring expiratory carbon monoxide (CO). Material and methods We enrolled 103 patients with early glottic carcinoma (T1N0/T2N0 = 79/24) who underwent conventional radiotherapy between 2005 and 2016. The median age was 70 years. Pathologically, all patients had squamous cell carcinoma. Since 2009, we confirmed smoking cessation before radiation therapy by medical interviews. Since 2014, we measured expiratory CO to strictly monitor smoking cessation. The patients were divided according to diagnosis years: ‘no cessation’ (2005–2008), ‘incomplete cessation’ (2009–2013), and ‘complete cessation’ (2014–2016). We retrospectively analyzed the local recurrence rate and disease-free survival (DFS). Results The median follow-up period was 60.1 months (range, 1.9–110.0 months). The 2-year local recurrence rate in the ‘complete cessation’ group was 5.3% and tended to be lower than that in the ‘incomplete cessation’ group (13.7%) and ‘no cessation’ group (21.2%). Multivariate analysis revealed that ‘no cessation’ was a risk factor for DFS (hazard ratio [HR] = 4.25) and local recurrence rate (HR = 16.5, p < .05) compared to ‘complete cessation.’ Discussion We confirmed that the ‘complete cessation’ group had better prognosis than the ‘no cessation’ group by monitoring expiratory CO during radiation therapy for early stage glottic carcinoma. Moreover, monitoring expiratory CO was easier and more suitable than conventional methods for evaluating smoking cessation because it provided real-time measurements.

Prospective study of recurrence at the surgical margin after wedge resection of pulmonary metastases

Pulmonary metastasectomy is a common treatment for selected patients with pulmonary metastases. Among pulmonary resections, wedge resection is considered sufficient for pulmonary metastases. However, a major problem with wedge resection is the risk of local recurrence, especially at the surgical margin. The aim of this prospective study was to explore the frequency of and the risk factors for recurrence at the surgical margin in patients who underwent wedge resection for pulmonary metastases. Between September 2013 and March 2018, 177 patients (220 lesions) with pulmonary metastases from 15 institutions were enrolled. We studied 130 cases (169 lesions) to determine the frequency of and risk factors associated with recurrence at the surgical margin in patients who underwent wedge resection. Moreover, we evaluated the recurrence-free rate and disease-free survival after wedge resection. A total of 81 (62.3%) patients developed recurrence. Recurrence at the surgical margin was observed in 11 of 130 (8.5%) cases. The 5-year recurrence-free rate was 89.1%. Per patient, multivariable analysis revealed that the presence of multiple pulmonary metastases was a significant risk factor for recurrence. Per tumor, distance from the surgical margin and tumor/margin ratio were risk factors for local recurrence. The 5-year disease-free survival rate was 34.7%, and the presence of multiple pulmonary metastases and small surgical margin were risk factors for disease-free survival by univariable analysis. Among patients who undergo wedge resection for pulmonary metastasis, patients with multiple pulmonary metastases tend to develop recurrence at the surgical margin.

Adjuvant oxaliplatin-based chemotherapy effect after treatment of colorectal hepatic metastasis.

PurposeWe aimed to investigate whether adjuvant oxaliplatin-based chemotherapy after treatment for hepatic metastasis affects recurrence or survival and to determine the risk factors for recurrence or survival.MethodsForty-six patients who underwent curative treatment for hepatic metastasis from colorectal cancer between July 2009 and December 2017 were included from a retrospectively collected patient database. Curative resection included hepatic resection, radiofrequency ablation (RFA), or a combination of both, followed by adjuvant chemotherapy with oxaliplatin-based chemotherapy.ResultsThirty-seven patients (80.4%) had colon cancer and 9 (19.6%) had rectal cancer. Twenty-six patients (56.5%) underwent hepatic resection, 7 (15.2%) RFA, and 13 (28.3%) hepatic resection and RFA. Thirty-two patients (69.6%) underwent chemotherapy after hepatic treatment. The recurrence incidence was 50% in the non-chemotherapy group and 46.9% in the chemotherapy group (P > 0.999). The incidence of death was 7.1% in the non-chemotherapy group and 18.8% in the chemotherapy group (P = 0.657). The recurrence risk factors were N stage (N0 vs. N2; P = 0.013, P = 0.005) and bilobed hepatic metastasis (P = 0.027, P = 0.009) in the univariate and multivariate analyses, respectively. However, chemotherapy after hepatic treatment was not a risk factor for disease-free survival (DFS) or overall survival (OS) in the univariate and multivariate analyses (P = 0.656 and P = 0.414, respectively; P = 0.510 and P = 0.459, respectively).ConclusionOxaliplatin-based adjuvant chemotherapy after colorectal hepatic metastasis treatment did not affect the DFS or OS. The N stage of the primary tumor and bilobed hepatic metastasis are risk factors for recurrence and death.

Clinical significance of visceral pleural and lymphovascular invasion in surgically resected adenosquamous lung cancer.

The aim of this study was to assess the relationship between visceral pleural invasion (VPI), lymphovascular invasion (LVI) and other clinicopathological characteristics and their prognostic impact on surgically resected adenosquamous carcinoma (ASC). We retrospectively reviewed 256 patients with radically resected ASC between January 2010 and December 2015. Patients were divided into 2 groups: those with VPI and those with LVI. The effects of VPI and LVI on disease-free survival and overall survival were evaluated, further stratified by tumour size and lymph node status. Finally, 213 patients with ASC were enrolled in our study. VPI was correlated with tumour location (P < 0.001), pT stage (P < 0.001) and pN stage (P = 0.012). LVI was related to age (P = 0.005) and pN stage (P = 0.003). Both VPI and LVI were adverse prognostic factors for disease-free survival (P = 0.008, P = 0.028) and overall survival (P = 0.005, P = 0.009) using the Kaplan-Meier method. In multivariable analysis only, VPI was an independent risk factor for disease-free survival [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.42-0.87; false discovery rate, adjusted P = 0.020] and overall survival (HR 0.60, 95% CI 0.42-0.86; false discovery rate, adjusted P = 0.017). When the prognostic value of VPI was stratified by tumour size and lymph node status, we observed that only patients with VPI in tumours ≤4 cm and patients with N0 status had a worse prognosis than those without visceral invasion (P < 0.05). VPI and LVI were poor prognostic factors in patients with ASC, but only VPI was an independent factor for survival, especially in patients with tumours ≤4 cm and pN0 status.

Clinical Assessment of Pediatric Patients with Differentiated Thyroid Carcinoma: A 30-Year Experience at a Single Institution.

BackgroundThyroidectomy is the typical treatment for pediatric thyroid carcinoma; total thyroidectomy is commonly performed. We aimed to report our experience at a single tertiary institution and to evaluate the risk factors for recurrence, especially based on surgical extent, in pediatric patients with differentiated thyroid carcinoma (DTC).MethodsA data of 94 pediatric patients who underwent thyroid surgery for DTC from January 1982 to December 2012 at Yonsei University Hospital (Seoul, Korea) were reviewed. The clinicopathologic features and surgical outcomes were retrospectively analyzed through complete chart reviews.ResultsThe mean age was 16.6 ± 3.0 (range, 5–19) years. Fourteen patients had recurrence. Tumor size >2 cm (hazard ratio [HR], 14.241; p = 0.011) and positive lymph nodes (HR, 1.056; p = 0.039) were significant risk factors for disease-free survival (DFS) in multivariate analysis. In Kaplan–Meier analysis, a statistically significant difference was noted in the DFS according to tumor size 2 cm (p < 0.001). However, the DFS was not significantly different between the bilateral total thyroidectomy (BTT) and less than BTT groups (p = 0.215).ConclusionsBTT remains the treatment of choice in pediatric patients with DTC. Lobectomy may be considered for patients with limited disease, including those with tumor size <2 cm, no suspicious lymph nodes, intrathyroidal lesion, and no multifocal disease.

Efficacy analysis of intraoperative radiotherapy in patients with early-stage breast cancer

BackgroundTo analyze the clinical efficacy of intraoperative radiotherapy (IORT) after breast-conserving surgery (BCS) in patients with early-stage breast cancer (BC), and to investigate the relationship between its influencing factors and clinical efficacy and prognosis.MethodsA total of 73 patients with early-stage BC who underwent IORT after BCS in our hospital were selected in this research.ResultsKaplan-Meier survival analysis was used to analyze the related factors of BCS and IORT of disease-free survival (DFS) and overall survival (OS). It was found that only age (χ2 = 14.035, P = 0.003) was statistically positively correlated with the patient’s DFS, and local recurrence and metastasis rate and mortality were higher in patients over 70 years old. Log rank test was used to analyze multiple factors. Only the diameter of the applicator (χ2 = 70.378, P < 0.05) was statistically significant with wound complications, and the larger the diameter, the higher incidence of wound complications. The remaining risk factors did not increase the incidence of wound complications. COX multivariate analysis showed that age was an independent risk factor for DFS rate and the risk factor had no significant effect on the OS rate of patients undergoing IORT after BCS.ConclusionsIORT may be a safe form of treatment for the selected patients with early-stage BC, and can achieve satisfactory esthetic effect. Larger applicator diameters may increase the incidence of wound complications. Age is an independent risk factor for DFS in early-stage BC patients undergoing IORT after BCS.

Prognostic Assessment of Cervical Cancer Patients by Clinical Staging and Surgical-Pathological Factor: A Support Vector Machine-Based Approach.

Introduction: The International Federation of Gynecology and Obstetrics (FIGO) staging system is considered the most powerful prognostic factor in patients with cervical cancer. In addition, other surgical-pathological risk factors have been demonstrated to have significance in predicting the prognosis of patients. Therefore, the purpose of this study was to investigate the effects of the FIGO staging system and surgical-pathological risk factors on the prognosis of cervical cancer patients.Methods: A retrospective study was performed on patients diagnosed with cervical cancer at FIGO stage IB1–IIA2. Kaplan–Meier, Cox proportional hazards regression analysis and the support vector machine (SVM) algorithm were used to assess and validate the high-risk factors related to recurrence and death.Results: A total of 647 patients were included. Kaplan-Meier analysis showed that five high-risk factors, including FIGO stage, status of pelvic lymph node, parametrial involvement, tumor size, and depth of cervical cancer, had a significant effect on the prognosis of patients. In multivariate analysis, pelvic lymph node metastasis (hazard ratio [HR] 2.415, 95% confidence interval [CI] 1.471–3.965), parametrial involvement (HR 2.740, 95% CI 1.092–6.872) and >2/3 depth of cervical invasion (HR 2.263, 95% CI 1.045–4.902) were three independent risk factors of disease-free survival. Pelvic lymph node metastasis (HR 3.855, 95% CI 2.125–6.991) and parametrial involvement (HR 3.871, 95% CI 1.375–10.900) were two independent risk factors for overall survival. When all five high-risk factors were assembled and used for classification prediction through SVM, it achieved the highest prediction accuracy of recurrence (accuracy = 69.1%). The highest prediction accuracy for survival was 94.3% when only using the two independent predictors (the pathological status of lymph nodes and parametrium involvement) by SVM classifiers. Among the 13 groups of intermediate-risk factor, the combination of tumor size, histology and grade of differentiation was more accurate in predicting prognosis than the intermediate-risk factors in the Sedlis criteria (recurrence: 86.8% vs. 60.0%; death: 92.0% vs. 71.6%).Conclusions: The combination of FIGO stage and surgical-pathological risk factors can further enhance the prediction accuracy of the prognosis in patients with early-stage cervical cancer. Histology and grade of differentiation can further improve the prediction accuracy of intermediate-risk factors in the Sedlis criteria.

The optimal time interval between the placement of self-expandable metallic stent and elective surgery in patients with obstructive colon cancer

A bridge to surgery (BTS) after a colonic stent for obstructive colon cancer has not been accepted as a standard treatment strategy. Also, there is no consensus regarding the optimal time interval for BTS. We aimed to identify the optimal timing for BTS after stent placement to decrease the oncologic risk. We retrospectively collected data of 174 patients who underwent BTS after stent placement for stage II or III obstructive colon cancer from five hospitals. We divided the patients into three groups based on the time interval for BTS after stent placement: within 7 days (Group 1), from 8 to 14 days (Group 2), and after 14 days (Group 3). The primary outcome was to compare the oncologic outcomes including overall survival (OS), disease-free survival (DFS), and recurrence rate (RR) among the three groups. Groups 1, 2, and 3 involved 75, 56, and 43 patients, respectively. Postoperative morbidity rates were 17.3%, 10.8%, and 9.3% in Groups 1, 2, and 3, respectively (P = 0.337). RRs were 16.0%, 35.7%, and 30.2% in Groups 1, 2, and 3, respectively (P = 0.029). In multivariate analysis, the time interval for BTS was an independent risk factor for DFS (P < 0.001; HR, 14.463; 95% CI, 1.458–3.255) and OS (P = 0.027; HR, 4.917; 95% CI, 1.071–3.059). In conclusion, the perioperative short-term outcome was not affected by the time interval of BTS. However, elective surgery within 7 days after colonic stent might be suggested to balance the short-term benefits and long-term oncologic risks.

Des-gamma-carboxy prothrombin affects the survival of HCC patients with marginal liver function and curative treatment: ACRoS1402.

Considering the initial treatment of hepatocellular carcinoma (HCC), the best prognostic index for Child-Pugh classes B and C (CP-BC) patients has not been yet established. This study aimed to elucidate the risk factors for disease-free survival (DFS) and overall survival (OS) in multicenter patients with a poor liver functional reserve after curative treatment. Between April 2000 and April 2014, 212 CP-BC patients who received treatment in five high-volume centers in Japan were included in this study. CP-B and C patients were 206 and 6, respectively. Cox proportional hazard regression analyses for DFS and OS were performed to estimate the risk factors. The mean observation time was 1132days. Mean Child-Pugh score and indocyanine green retention rate at 15min were 7.5 and 31.5%, respectively. Histological chronic hepatitis and liver cirrhosis were observed in 20% and 74% patients, respectively. In the multivariate analysis, the risk factors for DFS were des-gamma-carboxy prothrombin (DCP) [hazard ratio (HR), 1.6; P = 0.012] and treatment without liver transplantation. Moreover, DCP was identified as an independent risk factor for OS (HR, 1.7; P = 0.01). Tumor size, number, tumor thrombus, Milan criteria, liver cirrhosis, and treatment without liver transplantation were not identified as risk factors for OS. The 5-year OS in patients with high serum DCP levels (< 90mAU/mL) was significantly better than that in those with low serum DCP levels (P = 0.003). Serum DCP value before treatment predicted both DFS and OS in CP-BC patients with HCC.

Next generation sequencing reveals CCNE1 amplification as an independent prognostic factor for triple negative breast cancer (TNBC) patients.

558 Background: Triple negative breast cancer (TNBC) has the worst prognosis among breast cancer due to the heterogeneity as well as lack of better therapeutic approach. It remains controversial whether BRCA status is the predictor of survival in TNBC. Besides, both germline and somatic mutation may contribute to the prognosis. This study is to explore the potential predictors and therapeutic targets based on genetic data and clinicopathological parameters. Methods: Seventy-five TNBC patients were enrolled with approximately 2:1 based on BRCA status. Genetic data was analysed by comprehensive genomic profiling 508 key cancer related genes. DAVID was applied to perform pathway enrichment analysis of significant enriched genetic alterations. Cox regression model was applied to evaluate disease-free survival (DFS) and overall survival (OS). Immuno-chemistry (IHC) was used to validate clinically meaningful genetic alteration. Results: In this study, 27 germline mutations were detected, including 26 homologous recombination repair (HRR) pathway gene mutations and 1 mismatch repair gene mutation among them 16 BRCA1 mutations and 5 BRCA2 mutations were found. Germline HRR including BRCA1/2 mutation marginally affected DFS ( p = 0.0624 and 0.15, respectively). We found 480 somatic genetic alterations including 110 copy number variations (CNV). The median value of TMB was determined to be 4.1 Muts/Mb which divided 74 TNBC patients into TMB-low (TMB-l) and TMB-high (TMB-h) group. TMB-l group had inferior DFS to TMB-h ( p = 0.0457). CCNE1 (with 5% frequency) copy number gain was specifically enriched in TMB-l group but mutually exclusive with BRCA1/2 mutation. TNBC with CCNE1 gain displayed worse DFS ( p&lt; 0.0001). Cox multivariate regression analysis indicated CCNE1 gain was an independent risk factors for DFS [HR = 13.48 (95% CI 2.62-69.23), p= 0.002)]. Pathway analysis indicated CCNE1 harmed prognosis through regulation of transcription in G1/S phase. Expression of cyclin E1 was validated by IHC, which would be presented later. Conclusions: Comprehensive genomic profiling disclosed various potential prognostic markers for TNBC by integrating clinical characters. Especially, amplified CCNE1 may be a potential prognostic marker and therapeutic target. [Table: see text]

CircRNACCDC66 regulates cisplatin resistance in gastric cancer via the miR-618/BCL2 axis

Gastric cancer (GC) remains a serious threat to human health with a high cancer-related death rate and unsatisfactory treatment effects after curative resection, especially with advanced GC. Thus, exploration of the molecular mechanism of cisplatin (CDDP) resistance in GC is crucial. circCCDC66 (hsa_circ_0001313) expression was detected by quantitative reverse-transcription PCR in GC cell lines and tissues. The characteristics of circCCDC66 in CDDP resistance in GC were evaluated in vivo and vitro. We performed luciferin reporter assays, biotin-coupled RNA pull-downs and fluorescence in situ hybridization (FISH) to assess the relationship of miR-618 to circCCDC66. Function was determined by cytotoxicity assay, western immunoblotting and TUNEL. CircCCDC66 was overexpressed in CDDP-resistant cells and tissues. The circCCDC66 expression was significantly associated with malignancy and was an independent risk factor for disease-free survival (DFS) in GC patients treated by CDDP based chemotherapy. Data from in vitro and vivo experiments demonstrated that circCCDC66 inhibited apoptosis by targeting miR-618 and release of B-cell lymphoma-2 (BCL2). CircCCDC66 is an essential regulator in the development of CDDP resistance and may serve as a promising therapeutic target for GC patients. Otherwise, our study adds more evidence of circRNA functioning as a sequestering agent for miRNA.

Long non-coding RNA ERICH3-AS1 is an unfavorable prognostic factor for gastric cancer.

Long non-coding RNAs (lncRNAs) play important roles in gastric cancer (GC), but the mechanism is not fully clear. ERICH3-AS1 (ERICH3 antisense RNA1) is affiliated with the non-coding RNA class which has proven to be involved in the prognostic of GC, but the function of ERICH3-AS1 is still unclear. In this study, we aim to explore the potential function of ERICH3-AS1 in the development of GC and analyze the prognostic role of ERICH3-AS1 in GC. We found that the lncRNA ERICH3-AS1 was significantly up-regulated in GC tissues in the analysis of The Cancer Genome Atlas (TCGA) data; the Kaplan-Meier analysis showed that the higher the expression of ERICH3-AS1 was, the earlier the recurrence and the poorer the prognosis would be in patients. Cox univariate and multivariate analyses revealed that ERICH3-AS1 was a risk factor of disease-free survival (DFS) (p < 0.05) and overall survival (OS) (p < 0.05) of patients. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, it demonstrated that the ERBB pathways, the mitogen-activated protein kinase (MAPK) pathways, the MTOR pathways, p53 pathways and Wnt pathways were differentially enriched in ERICH3-AS1 high expression phenotype. Furthermore, the correlation analysis showed that ERICH3-AS1 had significant correlations with apoptosis-related proteins such as BCL2L10 and CASP14; cell cycle-associated proteins CDK14 and invasion and migration-associated proteins such as MMP20, MMP26 and MMP27. In summary, we identified that increased ERICH3-AS1 might be a potential biomarker for diagnosis and independent prognostic factor of GC. Moreover, ERICH3-AS1 might participate in the oncogenesis and development of tumors via cell cycle and apoptosis pathway mediated by ERBB, MAPK, MTOR, p53 and Wnt pathways.

Novel scoring system for recurrence risk classification of surgically resected G1/2 pancreatic neuroendocrine tumors - Retrospective cohort study.

Existing staging systems for pancreatic neuroendocrine neoplasms only provide accuracy in stratifying disease severity without enough sensitivity in prognosis predicting. Previously presented models mainly set overall survival as endpoint but ignore the importance of recurrence. Univariate and multivariate analyses were retrospectively conducted on the potential prognostic factors of 245 patients who underwent curable surgery of G1/2 pancreatic neuroendocrine tumors from December 2002 to May 2018 in our institute. Proposed model based on statistically significant factors were tested for recurrence risk classification estimation validity as measured by discrimination (receiver operator characteristic [ROC] curve and Harrell's c-index [HCI]) and calibration. Multivariate analyses found lymph node metastasis, larger tumor size and grade 2 independent risk factors of disease-free survival (DFS). The novel scoring system for recurrence risk classification sorted patients into three groups: score<15.4 for low risk (79.0%, 3- and 5-year recurrence risk 0.8% and 4.3%, median DFS not reached), score>15.4, <24.5 for intermediate risk (20.8%, 3- and 5-year recurrence risk 11.6% and 21.4%, median DFS 70 months) and score >24.5 for high risk (10.2%, 3- and 5-year recurrence risk 37.3% and 68.7%, median DFS 49 months).The area under curve (AUC) and HCI of our system were 0.871 and 0.929, superior to those of European Neuroendocrine Tumor Society (AUC 0.833, HCI 0.806). The presented system can be utilized to identify G1/2 pancreatic neuroendocrine tumors patients with high recurrence risk, which might be appropriate for peri-operative adjuvant therapy.

Yonsei Criteria, a Potential Linkage to Intratumoral Foxp3⁺/CD8⁺ Ratio for the Prediction of Oncologic Outcomes in Resected Left-Sided Pancreatic Cancer.

PurposeThis study sought to investigate associations among Yonsei criteria (tumor confined to the pancreas, intact fascia layer between the distal pancreas and the left adrenal gland and kidney, and tumor located more than 1–2 cm from the celiac axis) and tumor infiltrating lymphocytes in pancreatic cancer.Materials and MethodsPatients who underwent curative distal pancreatectomy due to left-sided pancreatic cancer from January 2000 to December 2011 were enrolled. Follow-up was completed September 30, 2015.ResultsFifty patients were enrolled. Having ≥ two metastatic lymph nodes (LNs, p=0.002), intraoperative transfusion (p=0.011), low levels of tumor infiltrating CD8+ T-cells (p=0.001), and a high Foxp3+/CD8+ ratio (p=0.009) were independent risk factors for disease-free survival. Not satisfying the Yonsei criteria (p=0.021), having ≥ two metastatic LNs (p=0.032), low levels of tumor infiltrating CD8+ T-cells (p=0.040) and a high Foxp3+/CD8+ ratio (p=0.032) were associated with unfavorable overall survival. High levels of CA19-9 and not satisfying the Yonsei criteria were significantly associated with a high Foxp3+/CD8+ ratio [Exp(β)=3.558; 95% confidence inverval: 1.000–12.658; p=0.050].ConclusionYonsei criteria may be clinically detectable biologic marker with which to predict immunologic status and survival in pancreatic cancer patients.

Evaluation of the Site and Frequency of Lymph Node Metastasis with Non-Functioning Pancreatic Neuroendocrine Tumor

Backgrounds: The optimal lymph node dissection range in patients with non-functioning pancreatic neuroendocrine tumors is not yet clear. In this study, we investigated the site and frequency of lymph node metastasis and the significance of lymph node dissection in patients with non-functioning pancreatic neuroendocrine tumors. Methods: This retrospective study analyzed 74 patients who underwent a curative pancreatectomy for non-functioning pancreatic neuroendocrine tumors between 2000 and 2016. The site and frequency of lymph node metastasis and clinicopathological factors were evaluated. Results: The rate of synchronous lymph node metastasis was 17.6%, with 11.1 and 29.4% for tumors with diameters of 10–19 mm and ≥20 mm, respectively. Lymph node metastasis was not observed for tumors with a diameter <10 mm. Lymph node metastasis was observed along the anterior (17a: 13.3%, 17b: 12.5%) and posterior (13a: 5.9%, 13b: 26.7%) surfaces of the pancreatic head and the superior mesenteric artery (14p: 12.5%, 14d: 7.7%) in patients with non-functioning pancreatic head neuroendocrine tumors, in the common hepatic (8a: 5.3%), splenic (10: 14.3%, 11p: 17.6%, 11d: 12.5%), and super mesenteric artery (14d: 14.3%) in patients with non-functioning pancreatic body neuroendocrine tumors, and only in the splenic artery (11p: 8.3%, 11d: 7.7%) in patients with non-functioning pancreatic tail neuroendocrine tumors. Grade 2 (HR = 6.21) and synchronous lymph node metastasis (HR = 10.4) were significant risk factors for disease-free survival. The 5-year disease-free survival was 95.7, 72.6, and 0% in patients with 0, 1, and 2 prognostic factors, respectively. Conclusions: This study clarified the site and frequency of lymph node metastasis and the optimal range of lymph node dissection in patients with non-functioning pancreatic neuroendocrine tumors.

Mechanotechnical faults and particular issues of anastomotic complications following robot-assisted anterior resection in 968 rectal cancer patients.

As most risk factors for anastomotic complications (AC) in rectal cancer patients appear to be noncorrectable, it is needed to find the correctable causes. Additionally, the outcomes of indocyanine-green fluorescence imaging (IFI) and robot-stapled anastomosis have yet been undetermined. This study retrospectively analyzed 968 consecutive patients with rectal cancer, who underwent curative robot-assisted anterior resections between 2010 and 2018. IFI parameters and stapling features in the surgical records were reviewed, and reconfirmed. AC occurred in 54 patients (5.6%), 34 (3.5%) with anastomotic leakage (AL) and 24 (2.5%) with anastomotic stenosis (AS). Mechanotechnical faults including defective stapling configurations, including angles lesser than or equal to 150° and outer deviation (more than half from the center of the circle) of linear staples, between the two linear staples were independently associated with AL (P < .001 each). IFI significantly reduced AL rate (2.5% vs 5.3%, P = .029) and AS rate (2% vs 18.8%, P = .006), respectively. Robot linear stapling enabled to maintain the obtuse angle during consecutive staplings and reduced console time. AL and AS were independent risk factors for disease-free survival (P = .02) and local recurrence (P = .03), respectively. AC were associated with some correctable causes, namely, mechanotechnical errors and lack of use of IFI.

Normal Alpha-Fetoprotein Hepatocellular Carcinoma: Are They Really Normal?

Introduction: serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had tried to explore the nature and behavior of this normal AFP HCC (N-HCC). The purpose of this study was to investigate the clinicopathological characteristics and survival outcome of N-HCC after operation. In addition, potential tumor markers for N-HCC were also sought in an attempt to augment diagnostic ability. Methods: between 2005 and 2015, patients with hepatocellular carcinoma who were treated with hepatectomy in Chang Gung Memorial Hospital Linkou branch were divided into two groups according to their preoperative serum AFP level (<15 ng/mL: NHCC; ≥15 ng/mL: abnormal AFP HCC (A-HCC)). Patient demographic data and clinicopathological variables were collected. Kaplan–Meier and Cox regression multivariate analyses were performed to identify significant risk factors for disease-free survival (DFS) and overall survival (OS) for N-HCC. ELISA and immunohistochemical (IHC) studies were employed to determine the diagnostic accuracy of various tumor markers. Results: a total of 1616 patients (78% male) who underwent liver resection for HCC were included in this study. Of them, 761 patients (47.1%) were N-HCC. N-HCC patients were significantly older with more comorbidities and less hepatitis virus infections. Furthermore, N-HCC had fewer early recurrences (49.6% vs. 60.8%, p < 0.001) and better DFS (44.6 months vs. 23.6 months, p < 0.001) and OS (94.5 months vs. 81.7 months, p < 0.001). Both ELISA and IHC studies demonstrated that glypican-3 (GPC3) would be a promising diagnostic tumor marker for N-HCC. Conclusion: N-HCC patients were significantly older and had less hepatitis virus infections or cirrhosis. Their tumors tended to be smaller, less vascular invaded, and well-differentiated. The carcinogenesis of N-HCC may thus not be identical to that of typical HCC. GPC3 would be a promising tumor marker for diagnosing N-HCC. Further study is warranted to validate our findings.

Decreased expression levels of ELOVL6 indicate poor prognosis in hepatocellular carcinoma.

The present study aimed to investigate the expression of elongation of very long-chain fatty acids family member 6 (ELOVL6) in hepatocellular carcinoma (HCC) tissues, and to determine its role in the development of HCC. A total of 377 HCC specimens were collected for tissue microarray and immunohistochemistry analyses. The ELOVL6 IHC score for HCC tissues was 0.97±0.71, which was significantly lower than that of the matched adjacent normal tissues (1.32±0.68; P<0.001). Patients with low levels of ELOVL6 expression were older (P=0.014) and possessed larger sized tumors (P=0.039) than patients with high expression levels. Additionally, Kaplan-Meier analysis revealed that patients with low ELOVL6 expression levels also had significantly poorer overall (P<0.001) and disease-free (P=0.029) survival times, and a greater probability of recurrence. The tumor size, tumor-node-metastasis (TNM) stage, vascular invasion and ELOVL6 expression were all shown to be prognostic variables for overall survival in patients with HCC. Multivariate analysis revealed that vascular invasion (P<0.001), TNM stage (P<0.001) and ELOVL6 expression (P=0.001) were independent prognostic variables for overall survival. In addition, vascular invasion (P=0.032) and ELOVL6 expression (P=0.041) were independent risk factors for disease-free survival, and vascular invasion (P=0.019) and ELOVL6 expression (P=0.045) were independent risk factors associated with HCC recurrence. The present study revealed that in patients with HCC, ELOVL6 expression level was reduced in HCC tissues, and that higher ELOVL6 expression levels correlated with longer survival times. This indicates that ELOVL6 may serves as an independent marker of poor patient outcome.

LINC00460 Hypomethylation Promotes Metastasis in Colorectal Carcinoma.

Introduction: Epigenetic alterations and aberrantly expressed long noncoding RNAs (lncRNAs) are pervasive in colorectal cancer (CRC) tumorigenesis. DNA methylation could control lncRNA expression and play an important role in tumor initiation and progression. However, the DNA methylation that regulates lncRNAs in CRC remains poorly characterized.Materials and Methods: In our research, we integrated dysregulated expression and methylation of lncRNAs between colorectal tumor and adjacent mucosa tissues from The Cancer Genome Atlas database. With the use of this strategy, LINC00460, the most frequently epigenetically activated, was identified and further verified in the Cancer Cell Line Encyclopedia and Gene Expression Omnibus databases.Results: Patients with high expression of LINC00460 are prone to metastasis and are associated with poor prognosis. Abnormally expressed LINC00460 could be used as an independent prognostic risk factor for disease-free survival. Knockdown of LINC00460 promotes colon cancer cell invasion and migration in vitro.Conclusion: In summary, our results suggest that DNA methylation-regulated LINC00460 could promote CRC metastasis and serve as a potential therapeutic target for CRC.

Integrin-α7 expression positively correlates with CD44 and CD133 expressions, and its high expression associates with advanced tumor features as well as poor survivals in non-small cell lung cancer patients

Background: This study aimed to explore the correlation of integrin-α7 (ITGA7) with common cancer stem cell marker (CD44 and CD133) expressions, clinicopathological characteristics and survival profiles in non-small cell lung cancer (NSCLC) patients. Methods: Two hundred and seventy NSCLC patients who underwent resection were reviewed in this study and the expressions of ITGA7, CD44 and CD133 were detected using immunohistochemistry (IHC) assay in tumor tissue specimens. The clinical data (including age, gender, pathological grade, tumor size, lymph node metastasis (LYN), and TNM stage), survival data [including disease-free survival (DFS) and overall survival (OS)] were collected. Results: The numbers of NSCLC patients with ITGA7 high expression, CD44 high expression and CD133 high expression were 170 (63.0%), 241 (89.3%) and 37 (13.7%) respectively, and ITGA7 expression was positively associated with CD44 expression and CD133 expression. ITGA7 high expression was associated with higher pathological grade, larger tumor size, LYN and elevated TNM stage. However, there was no correlation of ITGA7 expression with age or gender. As for survival, patients with ITGA7 high expression presented reduced DFS and OS compared with those with ITGA7 low expression. In addition, multivariate Cox’s proportional hazards regression model analyses exhibited that ITGA7 high expression, higher pathological grade and LYN were independent risk factors for DFS and OS in NSCLC patients. Conclusions: ITGA7 expression positively correlates with CD44 and CD133 expressions, and its high expression associates with advanced tumor features as well as poor survivals in NSCLC.