Deficient DNA mismatch repair is associated with favorable prognosis in Thai patients with sporadic colorectal cancer

AIM:To determine the prognostic significance of deficient mismatch repair(d MMR) and BRAF V600 E in Thai sporadic colorectal cancer(CRC) patients.METHODS:We studied a total of 211 out of 405 specimens obtained from newly diagnosed CRC patients between October 1,2006 and December 31,2007 at Siriraj Hospital,Mahidol University.Formalinfixed paraffin-embedded blocks of CRC tissue samples w e re a n a l y ze d fo r d M M R b y d e t e c t i o n o f M M R protein expression loss by immunohistochemistry or microsatellite instability using polymerase chain reaction(PCR)-DHPLC.BRAF V600 E mutational analysis was performed in DNA extracted from the same archival tissues by two-round allele-specific PCR and analyzed by high sensitivity DHPLC.Associations between patient characteristics,MMR and BRAF status with diseasefree survival(DFS) and overall survival(OS) were determined by Kaplan-Meier survival plots and log-rank test together with Cox's proportional hazard regression.RESULTS:d MMR and BRAF V600 E mutations were identified in 31 of 208(14.9%) and 23 of 211(10.9%) tumors,respectively.d MMR was more commonly found in patients with primary colon tumors rather than rectal cancer(20.4% vs 7.6%,P =0.01),but there was no difference in MMR status between the right-sided and left-sided colon tumors(20.8% vs 34.6%,P = 0.24).d MMR was associated with early-stage rather than metastatic disease(17.3% vs 0%,P = 0.015).No clinicopathological features such primary site or tumor differentiation were associated with the BRAF mutation.Six of 31(19.3%) samples with d MMR carried the BRAFmutation,while 17 of 177(9.6%) with proficient MMR(p MMR) harbored the mutation(P = 0.11).Notably,patients with d MMR tumors had significantly superior DFS(HR = 0.30,95%CI:0.15-0.77; P = 0.01) and OS(HR = 0.29,95%CI:0.10-0.84; P = 0.02) compared with patients with p MMR tumors.By contrast,the BRAF V600 E mutation had no prognostic impact on DFS and OS.CONCLUSION:The prevalence of d MMR and BRAF V600 E in Thai sporadic CRC patients was 15% and 11%,respectively.The d MMR phenotype was associated with a favorable outcome.

Predictive significance of cancer related-inflammatory markers in locally advanced rectal cancer

BACKGROUND Locally advanced rectal cancer is treated using neoadjuvant chemoradiation(nCRT),followed by total mesorectal excision(TME).Tumor regression and pathological post-treatment stage are prognostic for oncological outcomes.There is a significant correlation between markers representing cancer-related inflammation,including high neutrophil-to-lymphocyte ratio(NLR),monocyteto-lymphocyte ratio(MLR),and platelet-to-lymphocyte(MLR)and unfavorable oncological outcomes.However,the predictive role of these markers on the effect of chemoradiation is unknown.AIM To evaluate the predictive roles of NLR,MLR,and PLR in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiation.METHODS Patients(n=111)with locally advanced rectal cancer who underwent nCRT followed by TME at the Minimally Invasive Surgery Unit,Siriraj Hospital between 2012 and 2018 were retrospectively analyzed.The associations between post-treatment pathological stages,neoadjuvant rectal(NAR)score and the pretreatment ratios of markers of inflammation(NLR,MLR,and PLR)were analyzed.RESULTS Clinical stages determined using computed tomography,magnetic resonance imaging,or both were T4(n=16),T3(n=94),and T2(n=1).The NAR scores were categorized as high(score>16)in 23.4%,intermediate(score 8-16)in 41.4%,and low(score<8)in 35.2%.The mean values of the NLR,PLR,and MLR correlated with pathological tumor staging(ypT)and the NAR score.The values of NLR,PLR and MLR were higher in patients with advanced pathological stage and high NAR scores,but not statistically significant.CONCLUSION In patients with locally advanced rectal cancer,pretreatment NLR,MLR and PLR are higher in those with advanced pathological stage but the differences are not significantly different.

Prognostic Relevance of Metabolic Dysfunction-associated Steatohepatitis for Patients with Chronic Hepatitis B

Background and Aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is prevalent in patients with chronic hepatitis B(CHB).The effect of the histologic MAFLD phenotype on long-term CHB outcomes is unknown.We performed a longitudinal study to determine the prognostic relevance of biopsy-proven hepatic steatosis and steatohepatitis for CHB patients.Methods:Clinical and laboratory data were obtained from CHB patients who underwent liver biopsy during 2002–2008 and were treated with antiviral drugs.A hepatopathologist reviewed the biopsy specimens.Cox proportional hazards regression was used to estimate the adjusted hazard ratio(aHR)of outcomes,including all-cause mortality,liver transplantation,and liver-related events.Results:In accordance with Brunt’s classification,408 patients had steatohepatitis(n=34),“steatosis but not steatohepatitis”(n=118),or“non-steatosis”(n=256).All steatohepatitis patients had features of metabolic dysfunction.Over a mean follow-up of 13.8±3.1 years,18 patients died or underwent liver transplantation.In multivariate-adjusted analysis,steatohepatitis(aHR,6.37;95%confidence interval[CI]:1.59–25.5)compared with non-steatosis and advanced fibrosis(aHR,11.3;95%CI:1.32–96.3)compared with no fibrosis were associated with overall mortality/liver transplantation.Thirty-five patients developed 43 liver-related events,among which 32 were hepatocellular carcinoma.These events were associated with steatohepatitis(aHR,5.55;95%CI:2.01–15.3)compared with non-steatosis and advanced fibrosis(aHR,6.23;95%CI:1.75–22.2)compared with no fibrosis.The steatosis but not steatohepatitis group had a nonsignificantly higher risk of overall mortality and liver-related events.Conclusions:Metabolic dysfunction-associated steatohepatitis increased the risk of long-term mortality/transplantation and liver-related events in CHB patients.