Survival of Patients with Floor of Mouth Squamous Cell Carcinoma Treated with Surgical Resection and Reconstruction

To identify predictors of survival in patients with floor of mouth Squamous Cell Carcinoma (FOMSCC) in order to improve patient selection for resource intensive resection and reconstruction procedures. A retrospective record review of patients who underwent resection and reconstruction for FOMSCC at Charlotte Maxeke Johannesburg Academic Hospital. Patient data were collected and analyzed with respect to age, sex, race, tobacco usage, alcohol usage, tumour stage and post-operative chemo-radiation. One- and five-year recurrence and survival rates were also evaluated. Within the study period, 20 patients were identified that were treated with resection and reconstruction for FOMSCC. The mean age at diagnosis was 56.85 years, with 70 percent of the sample being male and fifty percent being black. Amongst the sample, 90 percent of patients used tobacco and 60 percent were frequent alcohol users. The most common stage at diagnosis was stage IVA which was found in 40 percent of the sample. There were no significant factors associated with recurrence at 1 year. At 5 years, alcohol usage was a significant predictor of recurrence (P=0.044).There were no significant factors associated with death at 1 year however tumour stage at 5 years was a significant predictor (P=0.035). Out of 20 patients, five patients had recurrence. Total person-time was 72.9 person-years, with a mean follow-up time of 3.65 (SD 2.04) years per person. Out of 20 patients, nine patients died within 5 years (45%). Alcohol was the only statistically significant factor associated with increased mortality. Our findings suggest earlier diagnosis, and active treatment of early stage disease may be the best means of improving 5-year survival rates. Efforts to improve quality of care and manage limited resources should concentrate on choosing the appropriate disease stage for surgical management, improve cancer surveillance and strengthen referral system so as to improve early detection of disease and provide, social support and counselling for adjunctive habits such alcohol and tobacco use cessation which will improve patient outcomes.

S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study

Objective: Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on ENSAT tumour stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC. Design: Multicentre retrospective study on ACC patients who underwent adrenalectomy. Methods: The S-GRAS score was calculated as a sum of the following points: tumour Stage (1-2=0; 3=1; 4=2), Grade (Ki67 index 0-9%=0; 10-19%=1; ≥20%=2 points), Resection (R)-status (R0=0; RX=1; R1=2; R2=3), Age (<50yr=0; ≥50yr=1), Symptoms (no=0; yes=1), and categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell’s C-index and Royston-Sauerbrei’s R2D statistic. Results: We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index=0.73, R2D=0.30, and C-index=0.79, R2D=0.45, respectively, all P<0.01 vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n=481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5. Conclusion: The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).

Serum Metabolomic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman’s correlation and Kapan Meier tests were conducted for correlation and survival analyses, respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose and lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used to predict patient survival and inform treatment intervention.

Colorectal Cancer Prevalence and Survival in Castilla La Mancha (Spain). A Pilot Study

Background: Colorectal cancer is the most commonly diagnosed cancer type and the second cause of cancer death in Spain. The primary risk factor for colorectal cancer is age, with 90% of all diagnosed patients aged over 50 years. Prognosis mainly depends on tumour stage. Aim: Conduct a pilot Colorectal Cancer prevalence and survival study in Cuenca (Spain) since there are almost no studies based on small populations. This is the first pilot study about survival in screening of colorectal cancer carried out in hospitals in Castilla La Mancha. Methods and Results: Retrospective descriptive cohort study was performed to include patients with colorectal cancer diagnosed by colonoscopy between May 2015 and April 2016, and who were followed up for 48 months. The study considered sociodemographic and clinical data of the patients. Survival curves were estimated using the Kaplan-Meier method. The proportional hazard rate associated with age, gender, stage and presence of metastasis was calculated using the Cox regression method. 57 patients were included in the study. The mean follow-up was 45.5 months. Ten patients died during the study, in seven cases the cause was colorectal cancer. The percentage of patients alive at 48-month follow-up were 82.4%. Conclusion: Colon cancer is a high-prevalence pathology, with adenocarcinoma being the most common histology. The results seem to indicate that it affects men more frequently, mortality rises with tumour stage at diagnosis and declines with use of chemotherapy. We present a pilot study that could justify large-scale epidemiological studies for the regional surveillance and evolution of colorectal cancer in Spain.

Identification of 5 Hub Genes Related to the Early Diagnosis, Tumour Stage, and Poor Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis

Background. The majority of primary liver cancers in adults worldwide are hepatocellular carcinomas (HCCs, or hepatomas). Thus, a deep understanding of the underlying mechanisms for the pathogenesis and carcinogenesis of HCC at the molecular level could facilitate the development of novel early diagnostic and therapeutic treatments to improve the approaches and prognosis for HCC patients. Our study elucidates the underlying molecular mechanisms of HBV-HCC development and progression and identifies important genes related to the early diagnosis, tumour stage, and poor outcomes of HCC. Methods. GSE55092 and GSE121248 gene expression profiling data were downloaded from the Gene Expression Omnibus (GEO) database. There were 119 HCC samples and 128 nontumour tissue samples. GEO2R was used to screen for differentially expressed genes (DEGs). Volcano plots and Venn diagrams were drawn by using the ggplot2 package in R. A heat map was generated by using Heatmapper. By using the clusterProfiler R package, KEGG and GO enrichment analyses of DEGs were conducted. Through PPI network construction using the STRING database, key hub genes were identified by cytoHubba. Finally, KM survival curves and ROC curves were generated to validate hub gene expression. Results. By GO enrichment analysis, 694 DEGs were enriched in the following GO terms: organic acid catabolic process, carboxylic acid catabolic process, carboxylic acid biosynthetic process, collagen-containing extracellular matrix, blood microparticle, condensed chromosome kinetochore, arachidonic acid epoxygenase activity, arachidonic acid monooxygenase activity, and monooxygenase activity. In the KEGG pathway enrichment analysis, DEGs were enriched in arachidonic acid epoxygenase activity, arachidonic acid monooxygenase activity, and monooxygenase activity. By PPI network construction and analysis of hub genes, we selected the top 10 genes, including CDK1, CCNB2, CDC20, BUB1, BUB1B, CCNB1, NDC80, CENPF, MAD2L1, and NUF2. By using TCGA and THPA databases, we found five genes, CDK1, CDC20, CCNB1, CENPF, and MAD2L1, that were related to the early diagnosis, tumour stage, and poor outcomes of HBV-HCC. Conclusions. Five abnormally expressed hub genes of HBV-HCC are informative for early diagnosis, tumour stage determination, and poor outcome prediction.

Cytochrome 4Z1 Expression Is Correlated with Poor Prognosis in Patients with Cervical Cancer

Background: cervical cancer is one of the most common malignancies in women worldwide and its management remains challenging and complex. As Cytochrome4Z1 (CYP4Z1) is overexpressed in many tumours, its expression in cervical cancer is unknown. Therefore, the present study aimed to evaluate CYP4Z1 expression in cervical cancers. Methods: CYP4Z1 expression was immunohistochemically assessed in 100 cases of cervical cancers along with ten normal cervix tissues, and the enzyme’s relationship to several clinicopathological features and survival was explored. Results: CYP4Z1 was strongly expressed in 55% of cervical cancer patients. Normal cervix samples were negative for CYP4Z1 expression. Importantly, this expression was significantly found in patients with the late stage of the disease, lymph node metastasis, and high tumour invasion (p < 0.05). Interestingly, CYP4Z1 expression was significantly correlated with shorter survival times of cervical cancer patients. Univariate analysis showed that CYP4Z1 expression, tumour stage, lymph node metastasis, and tumour invasion were significantly correlated with patient survival (p < 0.05). The multivariate analysis revealed that only CYP4Z1 expression and tumour stage were significantly correlated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is associated with cervical cancer patients’ survival and may serve as an independent predictor of poor prognosis in cervical cancer patients.

Metabolic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman&rsquo;s correlation and Kapan Meier tests were conducted for correlation and survival analyses respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose, lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used in predicting patient survival and in informing treatment intervention.

Negative impact of COVID-19 associated health system shutdown on patients diagnosed with colorectal cancer: a retrospective study from a large tertiary center in Ontario, Canada.

Background: In March 2020, a directive to halt all elective and non-urgent procedures was issued in Ontario, Canada because of COVID-19. The directive caused a temporary slowdown of screening programs including surveillance colonoscopies for colorectal cancer (CRC). Our goal was to determine if there was a difference in patient and tumour characteristics between CRC patients treated surgically prior to the COVID-19 directive compared to CRC patients treated after the slowdown. Methods: CRC resections collected within the Champlain catchment area of eastern Ontario in the six months prior to COVID-19 (August 1, 2019-January 31, 2020) were compared to CRC resections collected in the six months post-COVID-19 slowdown (August 1, 2020-January 31, 2021). Clinical (e.g. gender, patient age, tumour site, clinical presentation) and pathological (tumour size, tumour stage, nodal stage, lymphovascular invasion) features were evaluated using chi-square tests, T-tests and Mann-Whitney tests where appropriate. Results: 343 CRC specimens were identified (175 pre-COVID-19, 168 post-COVID-19 slowdown). CRC patients treated surgically post-COVID-19 slowdown had larger tumours (44 mm vs. 35 mm; p = 0.0048) and were more likely to have presented emergently (24% vs .10%; p < 0.001). While there was a trend towards higher tumour stage, nodal stage, and clinical stage, these differences did not reach statistical significance. Other demographic and pathologic variables including patient gender, age, and tumour site were similar between the two cohorts. Interpretation: The COVID-19 slowdown resulted in a shift in the severity of disease experienced by CRC patients in Ontario. Pandemic planning in the future should consider the long-term consequences to cancer diagnosis and management.

Clinicopathological and Prognostic Significance of LINC00673 in Human Malignancy: A Review and Meta-analysis

Background: We conducted this research to investigate the relationship between linc00673 expression and prognosis and clinicopathological parameters in human malignancies. Methods: The PubMed, Embase, WOS and CNKI databases were used to collect eligible research data before January 4, 2021. Meta-analysis was performed using Stata 12.0 software. Pooled ORs (odds ratios) or HRs (hazard ratios) and their 95% CIs were calculated to evaluate the association of linc00673 expression with survival outcomes and clinical parameters. Results: We finally included 17 articles and a total of 1539 cases for the meta-analysis. The results indicated that linc00673 was significantly correlated with T stage (P=0.006), tumour stage (P&lt;0.001), lymph node metastasis (P&lt;0.001), and distant metastasis ( P&lt;0.001). In addition, the results suggested that elevated linc00673 expression predicted a poor overall survival time (P=0.034) and acted as an independent prognostic factor (P&lt;0.001) for OS in patients with malignancy. Although potential evidence of publication bias was found in the studies on OS in relation to tumour stage in the multivariate analysis, the trim-and-fill analysis confirmed that the results remained stable. Conclusion: Overexpression of linc00673 was significantly correlated with shorter OS time in patients with malignant tumours. Moreover, the increased expression level of linc00673 was significantly correlated with T stage, tumour stage, lymph node metastasis, and distant metastasis. The results presented in this article revealed that linc00673 might be involved in the progression and invasion of malignancy and serve as a novel prognostic biomarker and potential therapeutic target for malignancy.

Study of pre-operative neutrophil–lymphocyte ratio in urothelial carcinoma

Objectives Neutrophil–lymphocyte ratio (NLR), as an indicator of heightened systemic inflammatory response, predicts increased disease burden and poor oncological outcomes in urothelial carcinoma (UC). The study was undertaken with an aim to evaluate the association of NLR with clinicopathological variables and survival outcomes. Methods A total of 80 patients of UC were enrolled in the current retrospective study. Pre-operative NLR (within one month prior to the procedure), patient age, sex, tumour grade, pathological stage, recurrence free survival (RFS), progression free survival (PFS) and cancer specific survival (CSS) were recorded. We chose a cut-off value of 2.7 for NLR and patients were divide into two groups (NLR <2.7 and ≥2.7). Results NLR ≥2.7 was significantly associated with advanced tumour stage (p=0.001), but not with tumour grade (p=0.116). Progression (p=0.032) and death rates (p=0.026) were high in patients with NLR ≥2.7. Mean RFS (p=0.03), PFS (p=0.04) and CSS (p=0.04) were reduced in patients with NLR ≥2.7. On univariate analysis, NLR ≥2.7 predicted worse RFS (HR=2.928, p=0.007), PFS (HR=3.180, p=0.006) and CSS (HR=3.109, p=0.016). However, it was not an independent predictor of outcomes on multivariate analysis. Conclusions Tumour stage and grade are the only independent predictors of RFS, PFS and CSS. High NLR at a cut-off value of ≥2.7 is associated with advanced pathological stage, but does not have an independent predictive value for RFS, PFS and CSS.