Meta-analysis of the prognostic value of pretreatment serum ferritin in hepatobiliary and pancreas (HBP) cancers

Background and objectivesStudies have shown that serum ferritin (SF) has unfavourable prognostic value in hepatobiliary and pancreas (HBP) cancers. This meta-analysis aimed to comprehensively assess the prognostic role of pretreatment SF in patients with HBP cancers.MethodsEligible studies published before January 2020 were obtained through a comprehensive search in the PubMed, Web of Science, Cochrane Library and EMBASE databases. Pooled HRs and 95% CIs were then employed as effect sizes.ResultsSeven studies comprising 1244 patients were pooled. Elevated pretreatment SF was associated with worse overall survival (OS) (HR 1.60, 95% CI 1.36 to 1.88, p<0.001) and recurrence-free survival/progression-free survival/time to recurrence (HR 1.70, 95% CI 1.15 to 2.52, p=0.008). Significant prognostic value of elevated pretreatment SF on OS was detected in the subgroups regardless of the cancer type, race, SF cut-off value, tumour-node-metastasis stage and Newcastle-Ottawa Scale score.ConclusionElevated pretreatment SF was associated with worse survival outcome of patients with HBP cancers. As such, it may serve as a novel prognostic biomarker for HBP cancers.

Impact of an organised population screening programme for colorectal cancer: Measurement after first and second rounds

Objective The first and second rounds of the Basque programme for organised colorectal cancer screening were implemented between 2009 and 2014. Our objective was to measure the changes in incidence, tumour, node, metastasis staging distribution and tumour, node, metastasis-adjusted survival of patients with colorectal cancer from 2003 to 2014. Method Colorectal cancer cases with screening (patients <70 years old) and without screening (patients ≥70 years old) were compared during three four-year periods: 2003–2006, 2007–2010 and 2011–2014 (fully implemented phase). Cox regression, five-year relative survival and cancer probability of death were calculated for each four-year period, age group and tumour, node, metastasis stage. Adjusted incidence rates were analysed by joinpoint regression. Results In an analysis of 23,301 cases of colorectal cancer, the incidence in patients younger than 70 years in 2013 showed a 17% annual decrease. The survival hazard ratios for stages I, II and III for 2003–2006 and 2007–2010 were compared to those for 2011–2014. From the first to the third period, diagnosis in the early stages (I and II) rose from 45.1% to 50.9% in the younger patient group and remained stable in the older group (49.6% and 49.4%). Additionally, the five-year relative survival rate increased significantly from 0.67 to 0.82 in those patients younger than 70 years, whereas in patients 70 years or older the rate did not change significantly (0.61 and 0.65). Conclusion The screening reduced incidence and improved survival by anticipating the diagnosis and by reducing mortality for each tumour, node, metastasis stage in the target population. The effect on survival could also be due to lead-time bias.

Autotaxin upregulated by STAT3 activation contributes to invasion in pancreatic neuroendocrine neoplasms

Although the upregulation of autotaxin (ATX) is associated with many solid tumours, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The expression of ATX in pNEN tissues and pNEN cell line BON1 was analysed by Western blot, PCR and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with siRNAs against ATX or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The following results were obtained. The expression of ATX in pNEN tissues was significantly increased compared with that in normal pancreatic tissues. High ATX expression was strongly correlated with tumour grade, lymph node metastasis and tumour-node-metastasis stage. Furthermore, ATX downregulation notably inhibited the metastatic capacity of pNEN cells, whereas STAT3 knockdown was found to downregulate the expression of ATX. ATX expression was upregulated in BON1 cells upon stimulation with IL-6, and this was accompanied by activation/phosphorylation of STAT3. Western blot analysis of human pNEN tissue extracts confirmed increased ATX expression and STAT3 phosphorylation with elevated expression levels of IL-6. In conclusion, ATX is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with STAT3 activation.

Diagnostic and prognostic potential of serum miR-132/212 cluster in patients with hepatocellular carcinoma

Background It has been reported that both of the miR-132/212 (micro-RNA) cluster members, miR-132 and miR-212, are downregulated in hepatocellular carcinoma. Nevertheless, the expression pattern and clinical utility of serum miR-132/212 in hepatocellular carcinoma are still unknown. Methods In this study, serum concentrations of miR-132 and miR-212 were measured in 80 hepatocellular carcinoma patients, 51 controls with chronic liver diseases and 42 healthy volunteers by using quantitative real-time polymerase chain reaction. Results In hepatocellular carcinoma patients, serum concentrations of miR-132 and miR-212 were significantly reduced and strongly correlated (r = 0.603, p < 0.001). Receiver operator characteristic analyses showed that serum miR-132 and miR-212 might have a potential role in the diagnosis of hepatocellular carcinoma. Moreover, the combination of serum miR-132, miR-212 and alpha-fetoprotein improved the diagnostic efficiency for hepatocellular carcinoma, especially in sensitivity and negative predictive value. Serum miR-132 was associated with tumour differentiation degree ( p = 0.021) and tumour–node–metastasis stage ( p = 0.002); serum miR-212 correlated with tumour size ( p = 0.023) and tumour–node–metastasis stage ( p = 0.007). Kaplan–Meier analyses indicated poorer overall survival in hepatocellular carcinoma patients with lower serum concentrations of miR-132 ( p < 0.001) and miR-212 ( p = 0.005). Conclusions Our results suggest that both components of the miR-132/212 cluster have potential roles as non-invasive serum biomarkers for diagnosis and prognosis of hepatocellular carcinoma.

Expression of GRK2 and IGF1R in hepatocellular carcinoma: clinicopathological and prognostic significance

AimIt has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the clinicopathological and prognostic significance of GRK2 and IGF1R in HCC.MethodsExpression of GRK2 and IGF1R was first detected by tissue microarray-based immunohistochemistry in 156 patients with HCC. Staining results, termed the H-score, were then correlated with clinicopathological variables and patient survival. Finally, the prognostic value of GRK2 and IGF1R was validated in the publically available TCGA (The Cancer Genome Atlas) RNA-sequencing database.ResultsThe H-score of GRK2 staining (which was significantly lower in tumour than non-tumour tissue) was negatively associated with that of IGF1R with a reverse trend. No clinicopathological significance of the proteins was found except for a relationship between tumoral IGF1R expression and tumour–node–metastasis stage. In univariate analysis, high IGF1R expression predicted poor overall and disease-free survival, whereas GRK2 was not prognostic. In multivariate analysis, IGF1R was significant for overall survival. Furthermore, IGF1R was also of prognostic value in the TCGA database.ConclusionsOur data indicate that GRK2 and IGF1R show a negative correlation in HCC. IGF1R could be a potential marker of poor prognosis for this malignancy.

Intracellular expression profile and clinical significance of the CCR9–CCL25 chemokine receptor complex in nasopharyngeal carcinoma

Objectives:This study aimed to investigate the association of C-C chemokine receptor type 9 (CCR9) and C-C motif chemokine 25 (CCL25) expression levels with clinical and tumour–node–metastasis stage in nasopharyngeal carcinoma.Methods:A total of 42 nasopharyngeal carcinoma patients (nasopharyngeal carcinoma group) and 18 patients with a normal nasopharynx (control group) were included in this study. Tissues were collected during surgery and medical examinations. The CCR9 and CCL25 messenger RNA and protein levels were measured using quantitative reverse transcription polymerase chain reaction, Western blotting and immunohistochemical analysis.Results:CCR9 and CCL25 messenger RNA and protein levels were significantly increased in the nasopharyngeal carcinoma group compared with the control group (p < 0.05). Both CCR9 and CCL25 messenger RNA and protein levels were significantly higher in advanced-stage nasopharyngeal carcinoma (stages III and IV) patients compared with early-stage nasopharyngeal carcinoma (stages I and II) patients (p < 0.05).Conclusion:The extent of CCR9 and CCL25 upregulation in nasopharyngeal carcinoma correlates with the tumour–node–metastasis stage.

Salvage supracricoid laryngectomy after failed radiotherapy and partial laryngectomy

Background:A case of salvage supracricoid laryngectomy with cricohyoidoepiglottopexy after failed radiation therapy and vertical partial laryngectomy had successful oncological and functional outcomes. This is the first reported application of salvage supracricoid laryngectomy with cricohyoidoepiglottopexy after the failure of two major treatments.Case report:A 65-year-old man was referred for salvage supracricoid laryngectomy with cricohyoidoepiglottopexy. The right recurrent hemilarynx was successfully resected. After pexis, the right lobe of the thyroid gland was repositioned to overlap and reinforce the pexis gap and fill the devoid portion of the strap muscular closure. Multiple scattered foci (recurrent tumour–node–metastasis stage T2) were identified around the arytenoid cartilage and beneath the musculocutaneous flap. Four years after supracricoid laryngectomy with cricohyoidoepiglottopexy, the patient's recovery was following a favourable course and he had satisfactory laryngeal function.Conclusion:Appropriate case selection and proficient surgical skills were essential for a successful outcome. Head and neck surgeons should not be afraid to adopt functional preservation open surgical procedures in well-selected and well-motivated patients. A requirement for more challenging surgical procedures and meticulous rehabilitation processes should not exclude appropriate treatments from a surgeon's repertoire.

Age Interactions in Breast Cancer: An Analysis of a 10-Year Multicentre Study in China

OBJECTIVES: The effects of age at diagnosis on the clinical characteristics of breast cancer and trends over time were investigated in Chinese women. METHODS: Data from 4211 women with pathologically confirmed primary breast cancer collected between 1999 and 2008 for a multicentre retrospective study were analysed according to age at diagnosis. RESULTS: Age at diagnosis ranged from 21 to 86 years, with a mean of 48.7 years, and was shown to be significantly related to tumour size, lymph node status, hormone receptor status and human growth factor receptor-2 status, but not to pathological type or tumour, node, metastasis stage. The age-corrected proportion of patients aged 50 – 64 years at diagnosis increased significantly between 1999 and 2008. There was a significant difference in the age-corrected distribution of age at diagnosis in China compared with Western countries. CONCLUSIONS: Age at diagnosis is related to the clinical and pathological characteristics of breast cancer. The age at diagnosis in China increased over the decade from 1999 to 2008, but is still lower than in Western countries.

Significance of fascin expression in laryngeal squamous cell carcinoma

Objective:Fascin is an actin-binding protein which is expressed in the basal areas of healthy squamous epithelium. Although overexpression of fascin has been shown in many tumours, the relationship between fascin and laryngeal squamous cell carcinoma has not previously been investigated, to the best of our knowledge. This study aimed to investigate the relationship between fascin expression and tumour behaviour in 30 cases of laryngeal squamous cell carcinoma.Materials and methods:For all lesions, a section of paraffin-embedded tissue was immunohistochemically stained for fascin. The percentage of positive, stained cells was scored from one to five (one = 0–5 per cent, two = 6–25 per cent, three = 26–50 per cent, four = 51–75 per cent and five = 76–100 per cent), and the staining intensity from one to three (one = mild, two = moderate and three = strong). A total immunohistochemical fascin expression score was obtained by multiplying the staining percentage and intensity. The relationship between the total fascin score and each case's age, sex, tumour localisation, tumour–node–metastasis stage and differentiation was evaluated statistically.Results:Various amounts of fascin expression were observed in all cases. There was a statistically significant relationship between high levels of fascin expression (i.e. a total fascin score of 10 or more) and the cases' tumour stage (p = 0.022), node stage (p = 0.024) and clinical stage (p = 0.014). In addition, worsening tumour differentiation was associated with an increasing fascin score, but this finding was statistically insignificant.Conclusion:These results suggest that laryngeal squamous cell carcinomas with high levels of fascin expression may be more aggressive than those with low expression levels. Further studies with larger series are needed to support these results and to clarify rationales.

Treatment results for ethmoid sinus carcinoma

Objective:The aim of this study was to describe the results of treatment in patients with ethmoid sinus carcinoma.Materials and method:We performed a retrospective study of 34 patients with carcinoma of the ethmoid sinus, and collected the following data: age, sex, employment, tobacco and alcohol consumption, tumour-node-metastasis stage, treatment, and survival.Results:The mean patient age was 64 years. Seventy-six per cent of patients were men and 24 per cent women. Squamous cell carcinoma was the most frequent histological tumour type (44 per cent). Eleven patients were classified as T2, six as T3, six as T4a and 11 as T4b. Two patients (6 per cent) had nodal metastasis at the time of diagnosis. The anterior skull base was involved in 17 patients (50 per cent) and the anterior orbital contents were affected in seven patients (21 per cent). The five-year actuarial observed survival rate for all patients was 44 per cent.Conclusions:Combined treatment with surgery and post-operative radiotherapy permitted good local control in patients with ethmoid sinus carcinoma. We do not recommend prophylactic neck treatment for ethmoid sinus carcinoma.