Analysis of transcriptome in the relationship between expression of PRC1 protein and prognosis of patients with cholangiocarcinoma

Objective To investigate whether protein regulator of cytokinesis 1 ( PRC1), which is involved in the regulation of human carcinogenesis, contributes to poor prognosis in patients with cholangiocarcinoma (CCA). Methods Data and tissues from patients with CCA were retrospectively studied. Immunohistochemical staining and western blotting were used to evaluate and contrast the PRC1 expression profile at the protein level in CCA tumour and pericarcinomatous tissues from the same study population. Relationships between clinical characteristics and patient survival were observed using univariate and multivariate analyses. Correlations between PRC1 expression and clinical characteristics were analysed by logistic regression. Results A total of 45 patients were included. PRC1 expression was found to be upregulated in CCA cancer tissues versus pericarcinomatous tissues. Overexpression of PRC1 was shown to be related to tumour differentiation, tumour node metastasis staging and lymph node metastasis, and was also revealed to be an independent marker of poor CCA prognosis. Conclusions The present results suggest that PRC1 may be a prognostic and therapeutic biomarker for patients with CCA.

External validation of the N descriptor in the proposed tumour–node–metastasis subclassification for lung cancer: the crucial role of histological type, number of resected nodes and adjuvant therapy

OBJECTIVES Overlapping survival curves for N1b (multiple N1 stations), N2a2 (single N2 station + N1 involvement) and N2a1 (skip N2 metastasis) limit the current tumour–node–metastasis (TNM) node (N) subclassification for node involvement. We validated externally the proposed subclassification. METHODS Clinical records from a multicentric database comprising 1036 patients with pulmonary adenocarcinoma (ADC) or squamous cell carcinoma with N1/N2 involvement who underwent, from January 2002 to December 2014, complete lung resections were retrospectively reviewed. Patients were categorized according to the 8th TNM N subclassification proposal. Histological type, number of resected nodes (#RN) and adjuvant therapy (ADJ) were considered limiting factors. RESULTS No difference in the 5-year overall survival (-OS) was noted between N1b and N2a1 (49.6% vs 44.8%, P = 0.72); instead, the 5-year-OS was significantly improved in patients with squamous cell carcinoma (63% in N1b vs 30.7% in N2a1, P = 0.04). In patients with ADC, the 5-year-OS was better in those with N2a1 than with N1b (50.6% vs 37.5%, P = 0.09). When we compared N1b with N2a2, the 5-year-OS was statistically significant (49.6% vs 32.8%, P = 0.02); considering only patients with squamous cell carcinoma (63% vs 25.8%, P = 0.003), #RN >10 (63.2% vs 35.3%, P = 0.05) and without ADJ (56.4% vs 24.5%, P = 0.02), the 5-year-OS was significantly different. Differences were not significant for ADC, #RN <10 and ADJ. Finally, the 5-year-OS was statistically significant when we compared N2a1 with N2a2 of the total cohort (44.8% vs 32.8%, P = 0.04), in ADC (5-year-OS 50.6% vs 36.5%, P = 0.04) and #RN >10 (5-year-OS 49.8% vs 32.1%, P = 0.03) without ADJ. CONCLUSIONS Histological type, ADJ and #RN are relevant prognostic factors in N + non-small-cell lung cancer. Considering these results, we may better interpret the prognosis prediction limits of the proposed 8th TNM subclassification for the N descriptor.

Prognostic score for survival with pulmonary carcinoids: the importance of associating clinical with pathological characteristics

OBJECTIVES Lung carcinoids (LCs) are staged using the non-small-cell lung cancer tumour/node/metastasis staging system; the possibility of an LC-specific staging system is still being debated. The goal of our study was to construct a composite prognostic score for LC. METHODS From January 2002 to December 2014, data from 293 patients who underwent surgical treatment for LC in 7 research institutes were retrospectively analysed. A panel of established prognostic factors in addition to lymph node metastasis patterns (single/multiple N1–N2 station, skip metastasis, lobe specific), numbers of lymph nodes resected and the ratio between the numbers of metastatic lymph nodes and the numbers of lymph nodes resected (node ratio) were correlated to overall survival (OS) and disease-free survival (DFS). The log-hazard ratio (HR), obtained from the Cox model, was used to derive weighting factors for a continuous prognostic index, designed to identify differential outcome risks. The score was dichotomized according to maximally selected log-rank statistics. RESULTS Pathological analysis showed typical carcinoids in 223 (76.1%) and atypical carcinoids in 70 (23.9%) patients; the tumour/node/metastasis pattern was stage I in 72.4%, stage II in 18.1%, stage III in 9.5% and stage IV in 0.03% cases. The median numbers of lymph nodes resected was 12 (range 0–53); hilar and mediastinal node metastases were identified in 14% and 6.8% of cases, respectively. Overall, the 5-year OS and 5-year DFS rates were 90.6% and 76.7%, respectively. At multivariable analysis, sex, age, pathological T stage and node ratio were significantly related to a better OS; age, histological type, pathological T stage and node ratio were related to DFS. These factors were used to generate the prognostic score, which showed statistically significant differences between the high-risk and low-risk groups: 5-year OS = 96.6% if score <3.1 vs 63.5% if score ≥3.1 [P < 0.0001; HR 17.56, 95% confidence interval (CI) 5.45–56.53]; 5-year DFS 92.3% if score <1.5 vs 52.5% if score ≥ 1.5 (P < 0.0001; HR 7.95, 95% CI 3.48–18.16). CONCLUSIONS The proposed prognostic scores seem to be effective in predicting outcomes for patients with LCs.

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.

Conversion surgery for positive peritoneal washing cytology in pancreatic cancer

Positive peritoneal washing cytology (PPC) of pancreatic carcinoma is defined as distant metastasis in the American Joint Committee on Cancer or Union for International Cancer Control’s tumour, node, metastases classification. However, surgical resection was believed to be the only method that prolong survival; thus, many institutions perform pancreatectomy for PPC, despite the unfavourable prognosis. Therefore, a more preferable alternative treatment for PPC is required. A 64-year-old man with resectable pancreatic tail cancer presented to our hospital. PPC was detected at first laparotomy; thus, pancreatectomy was avoided and gemcitabine with nabpaclitaxel (GnP) was administered. After four courses of GnP treatment, PPC converted to negative, as evaluated by abdominal port cytology. Thus, distal pancreatectomy was performed, and R0 resection was achieved. He has been healthy for more than 24 months since the first laparotomy. Initial chemotherapy with the intention of converting the cytological status followed by surgical treatment might become a useful treatment strategy for PPC.

Update on eighth edition American Joint Committee on Cancer classification for cutaneous melanoma and overview of potential pitfalls in histological examination of staging parameters

Cutaneous melanoma causes most of the skin cancer deaths in the USA. Melanoma is the fifth most common cancer among men and the sixth most common cancer among women. The incidence of melanoma has risen sharply over the past three decades. In this review, which is informed by our extensive experience at a large cancer centre, we outline the key differences between the tumour, node and metastases staging criteria for cutaneous melanoma in the seventh and eighth editions of the AJCC Cancer Staging Manual. We also offer advice on how to assess the histophenotypic parameters that are relevant for staging, with a special focus on avoiding potential pitfalls, and how to report all the prognostically and therapeutically relevant histophenotypic parameters. Correct assessment and reporting of these clinically relevant histophenotypic parameters is of outmost importance for practising pathologists because these parameters help treating clinicians select the most appropriate personalised treatment for patients in this era of promising targeted and immunotherapies.

Score genético predice agresividad del cáncer de próstata.

Introducción: Establecer un score genético utilizando los polimorfismos de nucleótido único (SNPs) del gen RNAsel y regiones cromosómicas 8q24 y 17q12-24 en combinación con el antígeno específico de la próstata (PSA) para predecir la agresividad del cáncer de próstata (CaP).Pacientes y métodos: hombres con CaP tratados con prostatectomía radical. Se analizaron variables clínicas y patológicas: edad al diagnóstico, PSA al diagnóstico, el volumen tumoral (TV) y extensión extracapsular (ECE) según el TNM (tumour, node and metástasis) (ECE ≥T3) y score de Gleason. Desarrollamos un modelo de puntaje genético usando regresión logística multivariable.Resultados: se incluyeron 86 pacientes sometidos a prostatectomía radical. Edad promedio fue de 62 ± 7,5 años. El promedio de PSA fue de 11,3 ± 10,6 ng/mL. Treinta y un pacientes (36%) tuvieron ECE. La mediana del TV fue de 3,8 cc. Un PSA ≥ 10 ng/mL se asoció con una mayor tasa de ECE (p <0,05) y TV más alto (p = 0,032). En el análisis univariable, los pacientes con > 1 SNP tienen mayor riesgo de ECE que los pacientes con ≤ 1 SNP (42% vs. 10,5%, p = 0,01), y los pacientes con ≥ 3 SNP tienen más TV que los pacientes con <3 SNP (60% vs. 32%, p = 0,015). Se crearon dos modelos de riesgo usando el número de SNP y PSA ≥ o <10 ng/mL para predecir ECE (sensibilidad 67% y especificidad 84%) y TV (sensibilidad 59% y especificidad 70%).Conclusiones: El score genético presentado en este estudio es una herramienta novedosa para predecir indicadores de agresividad del CaP, como ECE y TV.

TRANSARTERIAL CHEMOEMBOLIZATION(TACE) EFFICACY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA(HCC): CAN SIGNIFICANT PROGNOSTIC FACTORS BE REVEALED?

Material and methods. A total of 125 patients(pts) with HCC (stage BCLC-B) underwent TACE from 2009 to 2016. If pts had been found inoperable, radiological intervention was used as monotherapy or in combination with systemic therapy at different stages of the disease. Results. Median overall survival (OS) for pts subjected to at least one TACE session was 20.5 months (95 per cent confidence interval 16.4-24.59). Such factors as ECOG status (р=0,012, RR= 1,65), protein synthesis (albumin >37 г/л; р=0,005, RR = 0,47) and detoxication (total bilirubin ≤ 14 мкмоль/л; р=0,037, RR = 1,64) hepatic functions, functional hepatic ability according to Child-Pugh classification (А vs. B; p=0,016, RR = 2,5) ALBI categories (A1 vs. A2 vs. A3; р=0,007, RR = 1,66) as well as HCC invasion: tumour size (р=0,001, RR=2,1), level AFP ≥ 5 IU/ml (р=0,003, RR 2,25), bilobar involvement (р=0,024; RR=1,64) independently influence OS. Pronounced TACE effect (р<0,001, RR 1,93) and Time before Progression duration were found to influence significantly the fatality rate. Multifactorial analysis for OS confirmed increased mortality (RR=1,92) if total bilirubin was ≥14 umol/L (р=0,018); Impaired hepatic functions according to ALBI (р=0,007) and Child-Pugh classification (р=0,002) are associated with significant OS reduction (RR 1.73 и 3,41respectively). HCC invasion (BCLC; р=0,03) AFP level ≥5 IU/ml (р=0,008, RR=2,26) and the biggest tumour node size >10 см (р=0,01, RR 1,95) independently increase mortality rate. Effective TACE (р<0,001) is associated with significant OS increase and mortality decrease. Conclusion. TACE is most effective if HCC pts have satisfactory condition and preserved liver function (Child Pugh A or ALBIA1) and limited intrahepatic invasion (BCLCA/B), with tumour size being... cm and normal AFP level. Under conditions of intrahepatic progression subsequent local therapy was found to be significantly associated with OS increase.