Hospital surgical volume and colorectal cancer survival in Norway: A nationwide cohort study

BackgroundStudies of hospital surgical volume and colorectal cancer survival are inconclusive. We investigated whether surgical volume was associated with survival of patients operated for colorectal cancer in Norway.MethodsUsing Cancer Registry of Norway data, we compared excess mortality from colorectal cancer by hospital surgical volume among 26,989 colon and 9779 rectal cancer patients diagnosed 2009–2020 and followed-up to 31.12.2021. Hospitals were divided into terciles according to their three-year average annual surgical volume; colon: low (< 22), middle (22–73), high (> 73); rectal: low (< 17), middle (17–38), high (> 38). We estimated excess hazard ratios (EHR) with flexible parametric models adjusted for age, year, stage, surgical urgency and surgery location (within/outside patient’s residential health trust).ResultsLow-volume hospitals had the highest proportion of late-stage or acutely operated colon cancer patients. Colon cancer patients operated at low- versus high-volume hospitals had significantly increased crude excess mortality (EHR = 1.30; 95 % CI = 1.14–1.48) but no difference after adjustment for age, year, and stage (EHR = 0.97; 0.85–1.11). High-volume hospitals had the highest proportion of late-stage rectal cancer patients and patients operated outside their residential area. Rectal cancer patients operated at low- versus high-volume hospitals did not have significantly different excess mortality before (EHR = 0.84; 0.64–1.10) or after (EHR = 1.03; 0.79–1.35) adjustment for age, year, stage, surgical urgency and surgery location. After accounting for case-mix, hospital surgical volume was not associated with excess mortality from colon (P = 0.40) or rectal cancer (P = 0.22).ConclusionLow hospital surgical volume was not associated with poorer colorectal cancer survival.     

Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis

BackgroundThe aim of this study was to investigate the association between statin use and survival in a population-based colorectal cancer (CRC) cohort and perform an updated meta-analysis to quantify the magnitude of any association.MethodsA cohort of 8391 patients with newly diagnosed Dukes’ A-C CRC (2009–2012) was identified from the Scottish Cancer Registry. This cohort was linked to the Prescribing Information System and the National Records of Scotland Death Records (until January 2015) to identify 1064 colorectal cancer-specific deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use were calculated using time dependent Cox regression models. The systematic review included relevant studies published before January 2016. Meta-analysis techniques were used to derive combined HRs for associations between statin use and cancer-specific and overall mortality.ResultsIn the Scottish cohort, statin use before diagnosis (HR = 0.84, 95% CI 0.75–0.94), but not after (HR = 0.90, 95% CI 0.77–1.05), was associated with significantly improved cancer-specific mortality. The systematic review identified 15 relevant studies. In the meta-analysis, there was consistent (I² = 0%,heterogeneity P = 0.57) evidence of a reduction in cancer-specific mortality with statin use before diagnosis in 6 studies (n = 86,622, pooled HR = 0.82, 95% CI 0.79–0.86) but this association was less apparent and more heterogeneous (I² = 67%,heterogeneity P = 0.03) with statin use after diagnosis in 4 studies (n = 19,152, pooled HR = 0.84, 95% CI 0.68–1.04).ConclusionIn a Scottish CRC cohort and updated meta-analysis there was some evidence that statin use was associated with improved survival. However, these associations were weak in magnitude and, particularly for post-diagnosis use, varied markedly between studies.     

Racial differences in colorectal cancer survival at a safety net hospital

BackgroundWhile racial disparity in colorectal cancer survival have previously been studied, whether this disparity exists in patients with metastatic colorectal cancer receiving care at safety net hospitals (and therefore of similar socioeconomic status) is poorly understood.MethodsWe examined racial differences in survival in a cohort of patients with stage IV colorectal cancer treated at the largest safety net hospital in the New England region, which serves a population with a majority (65%) of non-Caucasian patients. Data was extracted from the hospital’s electronic medical record. Survival differences among different racial and ethnic groups were examined graphically using Kaplan-Meier analysis. A univariate cox proportional hazards model and a multivariable adjusted model were generated.ResultsBlack patients had significantly lower overall survival compared to White patients, with median overall survival of 1.9 years and 2.5 years respectively. In a multivariate analysis, Black race posed a significant hazard (HR 1.70, CI 1.01–2.90, p = 0.0467) for death. Though response to therapy emerged as a strong predictor of survival (HR = 0.4, CI = 0.2-0.7, p = 0.0021), it was comparable between Blacks and Whites.ConclusionsDespite presumed equal access to healthcare and socioeconomic status within a safety-net hospital system, our results reinforce findings from previous studies showing lower colorectal cancer survival in Black patients, and also point to the importance of investigating other factors such as genetic and pathologic differences.     

Stress and survival after cancer: a prospective study of a Finnish population-based cohort

Stress has been suggested to reduce survival after cancer, but the results of previous studies have been contradictory. We investigated the hypothesis in a national cohort of adults in Finland. Of those who completed the Stressful Life Events scale and the Stress of Daily Activities scale, 1470 and 1882, respectively, later had cancer and were included in the analysis, covering 23 years of follow-up between 1982 and 2004. In Cox regression analysis, the multivariate hazard ratio (HR) was 0.99 (95% confidence interval [CI], 0.96-1.01) for total number of life events and the HR for the life change score was 0.99 (95% CI, 0.95-1.03). Further, the HR was 0.92 (95% CI, 0.69-1.22) for severe daily stress. Overall, the results of the current study do not support the hypothesis that stress reduces cancer survival.     

Antihypertensive medications and survival in patients with cancer: A population-based retrospective cohort study

Background: The association between antihypertensive medications and survival in cancer patients remains unclear. Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients. Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n = 4241), colorectal (n = 3967), breast (n = 4019) or prostate (n = 3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04–1.44) and lung cancer (HR: 1.11, 95% CI: 1.03–1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02–1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01–1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15–1.42), and prostate (HR 1.41, 1.2–1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64–0.98). Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.     

Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study

BackgroundPreclinical evidence from breast cancer cell lines and animal models suggest that aspirin could have anti-cancer properties. In a large breast cancer patient cohort, we investigated whether post-diagnostic low-dose aspirin use was associated with a reduction in the risk of breast cancer-specific mortality.MethodsWe identified 15,140 newly diagnosed breast cancer patients within the Scottish Cancer Registry. Linkages to the Scottish Prescribing Information System provided data on dispensed medications and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% CIs for breast cancer-specific and all-cause mortality by post-diagnostic low-dose aspirin use. HRs were adjusted for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of statins. Secondary analysis investigated the association between pre-diagnostic low-dose aspirin use and breast cancer-specific and all-cause mortality.ResultsPost-diagnostic users of low-dose aspirin appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.44, 95% CI 1.26, 1.65) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.92, 95% CI 0.75, 1.14). Findings were similar in analysis by increasing duration of use and in analysis of pre-diagnostic low-dose aspirin use.ConclusionIn this large nationwide study of breast cancer patients, we found little evidence of an association between post-diagnostic low-dose aspirin use and cancer-specific mortality.     

Statin use after esophageal cancer diagnosis and survival: A population based cohort study

BackgroundA recent epidemiological study of esophageal cancer patients concluded statin use post-diagnosis was associated with large (38%) and significant reductions in cancer-specific mortality. We investigated statin use and cancer-specific mortality in a large population-based cohort of esophageal cancer patients.MethodsNewly diagnosed [2009–2012] esophageal cancer patients were identified from the Scottish Cancer Registry and linked with the Prescribing Information System and Scotland Death Records (to January 2015). Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% confidence intervals (CIs) by post-diagnostic statin use (using a 6 month lag to reduce reverse causation) and to adjust these HRs for potential confounders.Results1921 esophageal cancer patients were included in the main analysis, of whom 651 (34%) used statins after diagnosis. There was little evidence of a reduction in esophageal cancer-specific mortality in statin users compared with non-users after diagnosis (adjusted HR = 0.93, 95% CI, 0.81, 1.07) and no dose response associations were seen. However, statin users compared with non-users in the year before diagnosis had a weak reduction in esophageal cancer-specific mortality (adjusted HR = 0.88, 95% CI, 0.79, 0.99).ConclusionsIn this large population-based esophageal cancer cohort, there was little evidence of a reduction in esophageal cancer-specific mortality with statin use after diagnosis.     

Association of socioeconomic status and receipt of colorectal cancer investigations: a population- based retrospective cohort study

Background

Although the Canadian health care system was designed to ensure equal access, inequities persist. It is not known if inequities exist for receipt of investigations used to screen for colorectal cancer (CRC). We examined the association between socioeconomic status and receipt of colorectal investigation in Ontario.

Methods

People aged 50 to 70 years living in Ontario on Jan. 1, 1997, who did not have a history of CRC, inflammatory bowel disease or colorectal investigation within the previous 5 years were followed until death or Dec. 31, 2001. Receipt of any colorectal investigation between 1997 and 2001 inclusive was determined by means of linked administrative databases. Income was imputed as the mean household income of the person''s census enumeration area. Multivariate analysis was performed to evaluate the relationship between the receipt of any colorectal investigation and income.

Results

Of the study cohort of 1 664 188 people, 21.2% received a colorectal investigation in 1997–2001. Multivariate analysis demonstrated a significant association between receipt of any colorectal investigation and income (p < 0.001); people in the highest-income quintile had higher odds of receiving any colorectal investigation (adjusted odds ratio [OR] 1.38; 95% confidence interval [CI] 1.36–1.40) and of receiving colonoscopy (adjusted OR 1.50; 95% CI 1.48–1.53).

Interpretation

Socioeconomic status is associated with receipt of colorectal investigations in Ontario. Only one-fifth of people in the screening-eligible age group received any colorectal investigation. Further work is needed to determine the reason for this low rate and to explore whether it affects CRC mortality.Colorectal cancer (CRC) is the most common cause of cancer-related death among nonsmokers in North America. In 2004 an estimated 19 200 Canadians will receive a diagnosis of CRC and 8400 will die from the disease.¹ Although the age-standardized incidence and mortality of CRC have been decreasing, the number of new cases is increasing because of the growing size of the elderly population.CRC screening reduces the incidence and disease-specific mortality,^2,3,4,5,6 is cost-effective^7,8 and is endorsed by many professional societies.^{9,10,11,12,13,14,15} In 1994 the Canadian Task Force on the Periodic Health Examination (now the Canadian Task Force on Preventive Health Care) concluded that there was insufficient evidence to support CRC screening in asymptomatic people over the age of 40 years.¹⁶ In the 2001 update of these guidelines⁹ fecal occult blood testing (FOBT) every 1 or 2 years or flexible sigmoidoscopy every 5 years was recommended for screening average-risk people 50 years of age or older; there was judged to be insufficient evidence to support colonoscopy as the initial screening test. Despite these endorsements the use of CRC screening remains suboptimal.^17,18,19The Canadian health care system covers all medically necessary services without user fees. Although equity has been achieved in certain areas,^20,21 low socioeconomic status (SES) is associated with a lower rate of use of cardiovascular procedures^22,23 and screening tests for breast and cervical cancer.^24,25,26 It is unknown whether SES affects the receipt of CRC screening investigations. This study assessed the association of neighbourhood income (a marker of SES) with the receipt of colorectal investigations in people eligible for screening who lived in Ontario.     

Socioeconomic status and non-melanoma skin cancer: A nationwide cohort study of incidence and survival in Denmark

Background: The two main types of non-melanoma skin cancer differ with the pattern of exposure to ultraviolet radiation (UVR): basal cell carcinoma (BCC) appears to be more closely related to intermittent solar exposure and sunburn, while the risk for squamous cell carcinoma (SCC) is a result of lifetime cumulated exposure to UVR. As these exposures may differ by social position, we investigated its role in the risk for and survival after BCC and SCC diagnosed in Denmark in 1994–2006 with follow-up through 2006. Methods: The analyses were based on 52,166 cases of BCC and 5033 cases of SCC in a cohort of 3.7 million people born between 1925 and 1976 and residing in Denmark in 1992–2006. Information on cancer cases and socioeconomic indicators were obtained from population-based registries. We used log-linear Poisson regression models to estimate incidence rate ratios and cumulative relative survival to estimate survival up to 10 years after the first incident cases of BCC and SCC. Results: High socioeconomic status, measured by both education and disposable income, was strongly associated with a higher risk for BCC, whereas there was no association between SCC and educational level and only a weak association with income. In general, relative survival after BCC was better than after SCC; the pattern of survival was not affected by socioeconomic indicators. Conclusions: The observed pattern of social status and risk for non-melanoma skin cancer differed substantially for the two cancer types, supporting the hypothesis that they may have different aetiologies.     

Colorectal cancer ascertainment through cancer registries,hospital episode statistics,and self-reporting compared to confirmation by clinician: A cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

BackgroundElectronic health records are frequently used for cancer epidemiology. We report on their quality for ascertaining colorectal cancer (CRC) in UK women.MethodsPopulation-based, retrospective cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Postmenopausal women aged 50–74 who were diagnosed with CRC during 2001–11 following randomisation to the UKCTOCS were identified and their diagnosis confirmed with their treating clinician. The sensitivity and positive predictive value (PPV) of cancer and death registries, hospital episode statistics, and self-reporting were calculated by pairwise comparisons to the treating clinician’s confirmation, while specificity and negative predictive value were estimated relative to expected cases.ResultsNotification of CRC events were received for 1,085 women as of 24 May 2011. Responses were received from 61% (660/1,085) of clinicians contacted. Nineteen women were excluded (18 no diagnosis date, one diagnosed after cut-off). Of the 641 eligible, 514 had CRC, 24 had a benign polyp, and 103 had neither diagnosis. The sensitivity of cancer registrations at one- and six-years post-diagnosis was 92 (95% CI 90–94) and 99% (97–100), respectively, with a PPV of 95% (95% CI 92/93–97). The sensitivity & PPV of cancer registrations (at one-year post-diagnosis) & hospital episode statistics combined were 98 (96–99) and 92% (89–94), respectively.ConclusionsCancer and death registrations in the UK are a reliable resource for CRC ascertainment in women. Hospital episode statistics can supplement delays in cancer registration. Self-reporting seems less reliable.     

Associations of branched-chain amino acids with parameters of energy balance and survival in colorectal cancer patients: results from the ColoCare study

Background

Branched-chain amino acids (BCAA) have been previously linked to survival in colorectal cancer (CRC) patients. It is unclear whether BCAAs are prognostic biomarkers or surrogate markers for energy balance.

Objectives

We aimed to determine correlations of BCAAs with markers of energy balance over time and to investigate prognostic significance of BCAAs in CRC.

Methods

We used urinary samples from newly diagnosed CRC patients [n?=?163; (stage I–IV)] from the ColoCare study in Heidelberg, Germany, collected at surgery (n?=?163), 6 (n?=?83) and 12 months follow-up (n?=?54). Isoleucine, leucine, valine, (2Z)-3-methylglutaconic acid (3HM), 2-ethylhydracrylic acid (2EA), 2-methyl-3-hydroxybutyrate (2M3H) were detected using gas-chromatography mass-spectrometry and proton-nuclear-magnetic-resonance spectroscopy. Partial correlation coefficients between BCAAs with body mass index, physical activity (metabolic equivalent) and muscle area were computed and adjusted for sex and age at diagnosis. We used Cox proportional hazard models to investigate overall survival (OS) after 24 months of follow-up.

Results

We did not observe significant correlations between BCAAs and parameters of energy balance at all time points (correlation ranges: BMI: r?=???0.13 to ??0.01; METs: r?=???0.14 to 0.02; dorsal muscle: r?=???0.03 to 0.10). BCAAs were not associated with risk of death in stage I–III (e.g., valine: HR_log2?=?1.62, p?=?0.25) or in stage IV tumors. Elevated concentrations of 2EA and 2M3H were significantly associated with OS, independent of stage (2EA: stage I–III: HR_log2?=?0.42, p?=?0.04; stage IV: HR_log2?=?0.51, p?=?0.01).

Conclusion

Our study suggests that BCAAs in colorectal cancer patients do not reflect parameters of energy balance and may be independently associated with overall survival.

     

Development and validation of two nomograms for predicting overall survival and cancer-specific survival in gastric cancer patients with liver metastases: A retrospective cohort study from SEER database

BackgroundGastric cancer is heterogeneous and aggressive, especially with liver metastasis. This study aims to develop two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of gastric cancer with liver metastasis (GCLM) patients.MethodsFrom January 2000 to December 2018, a total of 1936 GCLM patients were selected from the Surveillance, Epidemiology, and End Results Program (SEER) database. They were further divided into a training cohort and a validation cohort, with the OS and CSS serving as the study's endpoints. The correlation analyses were used to determine the relationship between the variables. The univariate and multivariate Cox analyses were used to confirm the independent prognostic factors. To discriminate and calibrate the nomogram, calibration curves and the area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used. DCA curves were used to examine the accuracy and clinical benefits. The clinical utility of the nomogram and the AJCC Stage System was compared using net reclassification improvement (NRI) and integrated differentiation improvement (IDI) (IDI). Finally, the nomogram and the AJCC Stage System risk stratifications were compared.ResultsThere was no collinearity among the variables that were screened. The results of multivariate Cox regression analysis showed that six variables (bone metastasis, lung metastasis, surgery, chemotherapy, grade, age) and five variables (lung metastasis, surgery, chemotherapy, grade, N stage) were identified to establish the nomogram for OS and CSS, respectively. The calibration curves, time-dependent AUC curves, and DCA revealed that both nomograms had pleasant predictive power. Furthermore, NRI and IDI confirmed that the nomogram outperformed the AJCC Stage System.ConclusionBoth nomograms had satisfactory accuracy and were validated to assist clinicians in evaluating the prognosis of GCLM patients.     

Improved survival in homozygous sickle cell disease: lessons from a cohort study.

OBJECTIVE: To examine whether simple interventions in a sickle cell clinic improve survival in sickle cell disease. DESIGN: Survival curve analysis and hazard ratios in a cohort study followed from birth. SETTING: MRC Laboratories (Jamaica) at the University of the West Indies, and Victoria Jubilee Hospital, Kingston, Jamaica. SUBJECTS: 315 patients with homozygous sickle cell disease detected during the screening of 100,000 consecutive non-operative deliveries between June 1973 and December 1981 at the main government maternity hospital, Kingston, Jamaica. INTERVENTIONS: Prophylactic penicillin to prevent pneumococcal septicaemia, parental education in early diagnosis of acute splenic sequestration, close monitoring in sickle cell clinic. MAIN OUTCOME MEASURES: Survival. RESULTS: Survival appeared to improve, the log rank test for trend comparing the first, second, and last third of the study reaching borderline significance (P = 0.05). Combined deaths from acute splenic sequestration and pneumococcal septicaemia-meningitis declined significantly (test for trend, P = 0.02). CONCLUSION: Early diagnosis and simple prophylactic measures significantly reduce deaths associated with homozygous sickle cell disease.     

Case-based prediction of survival in colorectal cancer patients

OBJECTIVE: To develop an approach to the prediction of survival in patients with colorectal cancer using nearest neighbor analysis and case-based reasoning. STUDY DESIGN: A total of 216 patients with full clinicopathologic records and five-year follow-up were the subjects of this study. They were divided into a core database of 162 cases and a test group of 54 cases, with follow-up on all patients. When the patient was still alive at the end of the follow-up period, censored survival time was used. For each of the test cases, the four closest neighbors from the database were retrieved and their median survival time recorded and used as the predicted estimate of survival. Case matching was based on a Euclidean multivariate distance measure for the three best predictor variables: patient age, Dukes stage and tubule configuration. Cases with the smallest distance from the test case were considered to be the most similar. The predicted survival times for the test cases were compared with the actual, observed survival in the test cases to determine the success of this approach. RESULTS: The results showed reasonable concordance between observed and predicted survival figures, although there was a large degree of spread. Classification of cases into < or = 60 and > 60 months' survival showed a correct classification rate of 63%. For the prediction of survival time, the distribution of differences between observed and predicted survival times for the uncensored test cases had a median value of--5 months but also showed a wide dispersion of values. Correlation of observed and predicted survival times, while not reaching statistical significance at P < .05, did show a strong positive association. CONCLUSION: Case-based approaches to the prediction of survival times in cancer patients are important. The results of the current study illustrate the difficulties in applying this approach to survival data and highlight the complexity of patient information and the inability to accurately predict patient outcome on a small subset of clinicopathologic features. While extensive work needs to be carried out to improve prediction power, this study illustrates the potential for case-based analyses. The ability to retrieve feature-matched cases from hospital patient databases has clear, independent advantages in patient management, but the ability to provide reliable, targeted prognostic estimates on individual cases should be a common goal in medical research.     

Ezrin expression and cell survival regulation in colorectal cancer

Colorectal cancer (CRC) is the second largest cause of cancer deaths in the United States. A key barrier that prevents better outcomes for this type of cancer as well as other solid tumors is the lack of effective therapies against the metastatic disease. Thus there is an urgent need to fill this gap in cancer therapy. We utilized a 2D-DIGE proteomics approach to identify and characterize proteins that are differentially regulated between primary colon tumor and liver metastatic deposits of the IGF1R-dependent GEO human CRC xenograft, orthotopically implanted in athymic nude mice that may serve as potential therapeutic targets against CRC metastasis. We observed increased expression of ezrin in liver metastasis in comparison to the primary colonic tumor. Increased ezrin expression was further confirmed by western blot and microarray analyses. Ezrin, a cytoskeletal protein belonging to Ezrin–Radixin–Moesin (ERM) family plays important roles in cell motility, invasion and metastasis. However, its exact function in colorectal cancer is not well characterized. Establishment of advanced GEO cell lines with enhanced liver-metastasizing ability showed a significant increase in ezrin expression in liver metastasis. Increased phosphorylation of ezrin at the T567 site (termed here as p-ezrin T567) was observed in liver metastasis. IHC studies of human CRC patient specimens showed an increased expression of p-ezrin T567 in liver metastasis compared to the primary tumors of the same patient. Ezrin modulation by siRNA, inhibitors and T567A/D point mutations significantly downregulated inhibitors of apoptosis (IAP) proteins XIAP and survivin that have been linked to increased aberrant cell survival and metastasis and increased cell death. Inhibition of the IGF1R signaling pathway by humanized recombinant IGF1R monoclonal antibody MK-0646 in athymic mouse subcutaneous xenografts resulted in inhibition of p-ezrin T567 indicating ezrin signaling is downstream of the IGF1R signaling pathway. We identified increased expression of p-ezrin T567 in CRC liver metastasis in both orthotopically implanted GEO tumors as well as human patient specimens. We report for the first time that p-ezrin T567 is downstream of the IGF1R signaling and demonstrate that ezrin regulates cell survival through survivin/XIAP modulation.     

Relative impact of earlier diagnosis and improved treatment on survival for colorectal cancer: A US database study among elderly patients

PurposesTo estimate what proportion of improvement in relative survival was attributable to smaller stage/size due to early detection and what proportion was attributable to cancer chemotherapy in patients with colorectal cancer (CRC).MethodsWe studied 69,718 patients with CRC aged ≥66 years in 1992–2009 from Surveillance, Epidemiology, and End Results registries. Study periods were categorized into three periods according to the major changes or advances in screening and chemotherapy regimens: (1) Period-1 (1992–1995), during which there was no evidence-based recommendation for routine CRC screening and 5-fluorouracil was the mainstay for chemotherapy; (2) Period-2 (1996–2000), during which evidences and guidelines supported the use of fecal occult blood test (FOBT) and sigmoidoscopy for routine CRC screening; and (3) Period-3 (2001–2009), during which Medicare Program added the full coverage for colonoscopy screening to average-risk individuals, and several newly developed chemotherapy regimens were approved. Outcome variables included the likelihood of being diagnosed at an early stage or with a small tumor size, and improvement in relative survival.ResultsCompared to period-1, likelihood of being diagnosed with early stage CRC increased by 20% in period-2 (odds ratio = 1.2, 95%CI: 1.1–1.2) and 30% in period-3 (1.3, 1.2–1.4); and likelihood of being diagnosed with small-size CRC increased by 60% in period-2 and 110% in period-3. Similarly, 5-year overall relative survival increased from 51% in period-1 to 56% in period-2 and 60% in period-3. Increase in survival attributable to migration in stage/size was 9% in period-2 and 20% in period-3, while the remaining survival improvement during period-2 and period-3 were largely attributable to more effective chemotherapy regimens (≥71.6%) and other treatment factors (≤25%).ConclusionsImprovements in CRC screening resulted in a migration of CRC toward earlier tumor stage and smaller size, which contributed to ≤20% of survival increase. Survival improvement over the past 2 decades was largely explained by more effective chemotherapy regimens (≥71.6%).     

Novel molecular classification of colorectal cancer and correlation with survival

IntroductionColorectal cancer (CRC) is one of the most common cancers worldwide. This study was designed to evaluate biological patterns, explore molecular classification and correlate with survival outcome in treatment naïve CRC patients.MethodsOver 11 years consecutive series of 435 CRC patients were operated on as primary surgical therapy. A total of 201 CRC patients were included, whose complete set of clinical information was available, and their good quality tumour blocks were retrieved. Immunohistochemistry was used for tumour analysis, and partitional clustering was performed using R software for cluster analysis.ResultsThe median age was 43 (range 10–85) years; adenocarcinoma was the most commonly seen histological type. The great majority had positive CK20, CEA, E-Cadherin, Ki67, CDX2, and p53 expression. There were four distinct molecular classes found, whereas Ki67, CDX2, and p53 play the main role in partitioning. Younger age negatively impacted survival; overall and disease-specific survival was 26 months only with 50 months’ longest survival.ConclusionColorectal cancer is a biologically heterogeneous disease with at least four distinct molecular patterns, where cell proliferation and gene repair mechanisms appear to play the key role.