Survival paradox between stage IIB/C and stage IIIA colon cancer: is it time to revise the American Joint Committee on Cancer TNM system?

INTRODUCTION: A survival paradox between T4N0 (Stage IIB/IIC) and Stage IIIA colon cancer exists, even after adjusting for adequate lymph node (LN) retrieval and receipt of adjuvant chemotherapy (C). We conducted a large hospital-based study to re-evaluate this survival paradox based on the newest 8th edition staging system. METHODS: The National Cancer Data Base was queried to evaluate 35,606 patients diagnosed with Stage IIB, IIC, and IIIA colon cancer between 2010 and 2017. The Kaplan-Meier method and log-rank test were used to compare unadjusted overall survival (OS). Multivariable Cox proportional hazards model was used to determine the association of stage with hazard ratios adjusted for relevant demographic and clinical variables including ≥ 12 LNs retrieved and receipt of adjuvant chemotherapy. P value < 0.05 was considered statistically significant. RESULTS: The 5-year OS for optimally treated stage IIIA colon cancer (receipt of C) was 84.3%, which was significantly higher than stage IIB/C (≥ 12 LNs retrieved + C) (72.8%; P < 0.0001). Stage was an independent predictor of OS. Among optimally treated Stage IIIA patients, T1N1 had the best survival (90.6%) while stage T4bN0 (stage IIC) had the worst (70.9%) (P < 0.0001). Compared to stage IIB, stage IIC had a 17% increased risk of overall death while stage IIIA had a 21% reduction in death (P < 0.0001). CONCLUSION: Stage IIB/C and Stage IIIA survival paradox persists even after accounting for receipt of adjuvant chemotherapy and adequate lymph node retrieval. Future iteration of the TNM system should take this paradox into consideration.

Rural versus urban commuting patients with stage III colon cancer: is there a difference in treatment and outcome?

BACKGROUND: To evaluate if there are differences in outcomes for patients with stage III colon cancer in those from urban vs. rural commuting areas. METHODS: Data were evaluated on patients diagnosed with stage III colon cancer between 2012 and2018 from the Louisiana Tumor Registry. Patients were classified into rural and urban groups. Data on overall survival, time from diagnosis to surgery and time from surgery to chemotherapy, and sociodemographic factors (including race, age, and poverty level) were recorded. RESULTS: Of 2652 patients identified, 2159 were urban (81.4%) and 493 rural (18.6%). No age difference between rural and urban patients (p = 0.56). Stage IIIB accounted for 66.7%, followed by IIIC (21.6%) and IIIA (11%), with a significant difference between rural and urban patients based on stage (p = 0.02). There was no difference in the extent of surgery (p = 0.34) or tumor size (p = 0.72) between urban and rural settings. No difference in undergoing chemotherapy (p = 0.12). There was a statistically significant difference in receiving timely treatment for hospital volume (p < 0.0001) and poverty level (p < 0.0001), but no difference in time from diagnosis to surgery (p = 0.48), and time from surgery to chemotherapy (p = 0.27). Non-Hispanic Blacks were less likely to receive timely treatment when compared with non-Hispanic Whites for both surgery and adjuvant chemotherapy, (aHR 0.91, 95% CI 0.83-0.99) and (aHR 0.86, 95% CI 0.77-0.97), respectively. There was no difference in Kaplan-Meier overall survival curves comparing rural vs. urban patients (p = 0.77). CONCLUSIONS: There was no statistical difference in overall survival, time to surgery, and time to adjuvant chemotherapy between rural and urban patients with Stage III colon cancer.

Positive impact of the Patient Protection and Affordable Care Act Medicaid expansion on Louisiana women with breast cancer.

BACKGROUND: Louisiana is one of the few Southern states that enacted the Medicaid expansion of the Patient Protection and Affordable Care Act (ACA). To the authors' knowledge, the issue of how this has affected the breast cancer landscape in Louisiana is unknown. The authors have postulated that ACA expansion had a positive impact for Louisiana women diagnosed with breast cancer. METHODS: Data from the Louisiana Tumor Registry regarding 14,640 women aged 20 to 64 years who resided in Louisiana and were diagnosed with American Joint Committee on Cancer stage 0 to stage IV breast cancer between 2012 and 2018 were analyzed. The study period was divided into 2 groups: 1) before ACA expansion (January 1, 2012-May 31, 2016); and 2) after ACA expansion (June 1, 2016-December 31, 2018). The chi-square test and multivariable logistic regression models were used to assess the impact of ACA expansion. A P value <.05 was considered statistically significant. RESULTS: After ACA expansion, the rate of uninsured patients decreased from 5.4% to 3.0% (P < .0001), and the rate of Medicaid recipients increased from 11.6% to 17.7% (P < .0001). The diagnosis of stage I breast cancer increased from 36.8% to 44.7% (P < .0001), whereas the diagnosis of stage III breast cancer decreased from 10.7% to 8.5% (P < .0001). The receipt of radiotherapy after breast-conserving surgery increased from 81.2% to 84.0% (P = .0035), and the receipt of radiotherapy within 90 days increased from 57.2% to 61.7% (P = .0012). After adjustment for sociodemographic and clinical variables, the models demonstrated that ACA expansion decreased the uninsured rate by 48% (odds ratio [OR], 0.52; 95% CI, 0.43-0.63), increased the diagnosis of early-stage disease (stage0 to stage II) by 27% (OR, 1.27; 95% CI, 1.15-1.41), increased receipt of radiotherapy after breast-conserving surgery by 19% (OR, 1.19; 95% CI, 1.03-1.37), and reduced the delay of receipt of radiotherapy by 16% (OR, 0.84; 95% CI, 0.74-0.95). CONCLUSIONS: ACA expansion in Louisiana reduced the uninsured rate, increased the diagnosis of early-stage disease, and increased access to treatment.

Ofatumumab demonstrates activity against rituximab-sensitive and -resistant cell lines, lymphoma xenografts and primary tumour cells from patients with B-cell lymphoma.

Ofatumumab is a new monoclonal antibody (mAb) targeting a novel membrane-proximal epitope on CD20. To better define ofatumumab's activity, we conducted pre-clinical studies in rituximab-sensitive cell lines (RSCL), rituximab-resistant cell lines (RRCL), ofatumumab-exposed cell lines (OECLs), primary lymphoma cells, and a lymphoma xenograft model. RRCL and OECL were generated by repeated exposure of sensitive cells to escalating doses of rituximab or ofatumumab ± human serum. Antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CMC) assays were performed to assess cellular sensitivity to rituximab or ofatumumab. Ofatumumab elicited a higher rate of CMC in RSCL, RRCL and primary tumour cells. The chronic exposure of lymphoma cells to ofatumumab resulted in rituximab resistance but less ofatumumab resistance. In an in vivo severe combined immunodeficiency mouse model of human lymphoma, ofatumumab prolonged median survival compared to rituximab. While rituximab CMC diminished with CD20 down-regulation in RRCL passages, ofatumumab activity in vitro diminished to a lesser degree. Our data suggest that ofatumumab is more potent than rituximab in rituximab-sensitive or rituximab-resistant models and has the potential to decrease the development of biological resistance in patients with repeated exposure to anti-CD20 mAbs.

Distinct cellular and therapeutic effects of obatoclax in rituximab-sensitive and -resistant lymphomas.

Bcl-2 proteins represent a rheostat that controls cellular viability. Obatoclax, a BH3-mimetic, has been designed to specifically target and counteract anti-apoptotic Bcl-2 proteins. We evaluated the biological effects of obatoclax on the anti-tumour activity of rituximab and chemotherapy agents. Obatoclax induced cell death of rituximab/chemotherapy-sensitive (RSCL), -resistant cell lines (RRCL) and primary tumour-cells derived from patients with B-cell lymphomas (N=39). Obatoclax also enhanced the activity of rituximab and had synergistic activity when combined with chemotherapy agents. The ability of Obatoclax to induce PARP cleavage varied between patient samples and was not observed in some RRCL. Inhibition of caspase activity did not affect obatoclax activity, suggesting the existence of caspase-independent death pathways. Autophagy was detected by LC3 conversion and/or electron microscopy in RRCL and in patient-derived tumour cells. Moreover, obatoclax activity was inhibited by Beclin-1 knockdown. In summary, obatoclax is an active Bcl-2 inhibitor that potentiates the activity of chemotherapy agents and, to a lesser degree, rituximab. Defining the molecular events triggered by obatoclax is necessary to further its clinical development and identify potential biomarkers that are predictive of response.

Value-based focused global population health management.

In 2018, approximately 18 million people worldwide were diagnosed with cancer and are predicted to double by 2040. The global quality chasm in improving health care worldwide requires "systems thinking" as the key to success. Aligning the goal around person-centered care captures the total needs of care of a population and not just disease categories. The integration of the Institute of Medicine's (IOM) six aims of quality termed "value-based focused" and population health management (PHM) provides all health care leaders grappling with improving the health care of the populations a framework for the communities they serve. In this context, the question becomes finding solutions to providing high quality, compassionate and patient-centered health care delivery. Over the last two decades, three paradigms have emerged; the six aims of quality, outcome-focused population health, and the "Quadruple Aim". We have termed the intersection of these concepts as Value-based focused Population Health Management (VBPHM). This review applies VBPHM across the geographic county and community levels in the United States. Specifically, we examine VBPHM at the county or county-equivalents and community levels within the United States. Lastly, the potential role of Community-based Participatory Research and it is applicability to our framework is discussed. VBPHM can comparably be applied globally to improve population health, especially in preventing and treating cancer better.

A discussion of the gut microbiome's development, determinants, and dysbiosis in cancers of the esophagus and stomach.

The microbiome refers to a population of microbes that colonize the skin, nasopharynx, oral cavity, gastrointestinal tract, and urogenital tract. The human microbiome consists of bacteria, archaea, fungi, viruses, and phages. Recent advances in genomic sequencing have catalyzed a deeper understanding of complex microbe-microbe and host-microbe interactions. Dysregulation of these interactions, or dysbiosis of the gastrointestinal tract, has been implicated in a growing list of pathologies including nonalcoholic fatty liver disease, cardiovascular disease, obesity, diabetes, depression, Parkinson's disease, autism, and various gastrointestinal cancers. Gastric and esophageal cancer, for example, continue to remain as two of the most common causes of cancer-related deaths worldwide, therefore there is an increased emphasis on investigating the role of dysbiosis on these cancers. In this review, we discuss the development and structure of the gut microbiome, its homeostatic and dysbiotic mechanisms, and the key microbes in esophageal and gastric carcinogenesis with a focus on bacterial biology. Further clarification of these pathways and discovery of diagnostic or therapeutic targets could have broad impacts on global subpopulations. It is important to understand the nature of the gastrointestinal tract microbiome and its potentional risk factors for dysbiosis in order to tailor its application to the individual patient and create an era of highly personalized, precision medicine.

Esophageal cancer: the rise of adenocarcinoma over squamous cell carcinoma in the Asian belt.

Esophageal cancer is a common cancer worldwide with a high associated mortality rate. Amongst the two most frequent subsets of disease, squamous cell carcinoma (SCC) and adenocarcinoma (AC), there has been an epidemiologic shift towards adenocarcinoma over the last few decades. However, squamous cell carcinoma still predominates worldwide. Within Western countries, obesity has been associated with an increase in esophageal AC. A striking report from the World Health Organization (WHO) stated that worldwide obesity has tripled since 1975. In 2016, the WHO reported that greater than 1.9 billion adults are overweight and over 650 million were obese. In this review our goal is to analyze the esophageal cancer trends of China, which is the largest contributor among the esophageal cancer "Asian belt." Our intent is to evaluate whether there is a correlation between the rise in esophageal adenocarcinoma and obesity in this esophageal cancer "hotspot." With further analysis, the high-risk populations that are identified can be targeted to implement preventative strategies. This focus will aid in decreasing the burden of esophageal cancer at the global health level by addressing preventative strategies, such as screening endoscopy and lifestyle modifications. For example, WHO developed a global action plan on physical activity in response to the rise in obesity worldwide. Prevention is key to decreasing the rate of esophageal adenocarcinoma as majority of cases are diagnosed in the late stages leading to high mortality rates.

Implications of the growing incidence of global colorectal cancer.

The expanding worldwide burden of colorectal cancer (CRC) is a significant public health issue. Understanding the shift in the geo-demographic, socioeconomic, environmental, and biogenetic distribution of CRC is paramount. The Human Development Index (HDI) measuring life expectancy, education, and gross national income is a composite index comparing health outcomes between countries. This has been shown to be a useful comparison tool in measuring the health dimension among high, middle, and low-income countries. CRC has a wide global distribution in incidence and mortality with majority of cases occurring in countries with a high or very high HDI. However, in developing countries and in those undergoing rapid socioeconomic growth, there has also been a marked rise in CRC rates as well. This pattern is noted globally and seems to correlate with increase in a country's specific HDI. Additionally, another unique pattern of CRC incidence has emerged with more cancers being diagnosed in adults younger than 50 years old. Further investigation is needed to determine CRC risks reduction and implementation of primary prevention and early detection strategies within different country specific healthcare systems. Globally, improvement in healthcare equality, access to medical care and screening for CRC particularly in resource-limited (low HDI) countries is essential.

Value-based chronic care model approach for vulnerable older patients with multiple chronic conditions.

"Old age, itself, is not a disease" (Suborne 2007). The rising rate of the global aging population is predicted to create a health care crisis within the next three decades. Vulnerable older adults suffer from multiple chronic conditions (MCCs) in addition to cognitive and physical decline during the process of aging resulting in an inability to optimally achieve self-management. In terms of resource utilization, complex inpatient, and outpatient care results in higher physician visits, polypharmacy, and higher prescription costs. Health literacy has become known as an important social determinant of health affecting the older population. Both reductions in health literacy and self-management are associated with poorer health outcomes. The patient activation measure (PAM) has been coined "a vital sign" to ascertain a patient activation level throughout the continuum of care with the introduction of an intervention's progress. In this review, we conceptualize a systematic approach of the development of a "tailored" integrated community and care team to develop a partnership in assisting senior adults with MCCs. Through this intervention the value-based chronic care model (CCM) and PAM allows for an adaptable integration between the activated patient, their caregivers, and the community. The Model for Improvement (MFI) serves as a well-recognized technique for developing and executing quality improvement strategies in this "tailored" engaged and activated individual and community care team approach in achieving health outcomes and quality of life among the vulnerable older adult population worldwide.

Social determinants of health associated with poor outcome for rural patients following resected pancreatic cancer.

BACKGROUND: The impact of rurality on outcome for patients who had resected pancreatic ductal adenocarcinoma (PDAC) is unclear. We hypothesize that poor outcomes for rural patients are associated with adverse social determinants of health (SDoH). The objective of this study is to assess the difference in overall survival (OS) of PDAC patients between rural, urban, and contributing factors. METHODS: A cohort of 25,536 patients diagnosed with stage I-III pancreatic adenocarcinoma from 2003 to 2011 and underwent resection were evaluated from the National Cancer Database. Socioeconomic/demographic, clinicopathological, and treatment variables were compared between rural and urban residences. The 5-year OS was calculated using the Kaplan-Meier method. The Cox regression model was used to assess factors associated with OS. P value <0.05 was considered significant. RESULTS: In univariate analysis, the rural residence was a predictor of poor OS. The 5-year OS for rural (N=4,389) and urban (N=21,147) was 18.8% (95% CI: 17.4-20.2%) and 22.3% (95% CI: 21.6-22.9%; P<0.0001), respectively. The risk of all causes of death was 10.3% higher (P<0.0001) in rural than urban patients. In multivariable analysis, rurality was not an independent predictor of OS (P=0.407). Independent predictors of worse OS included adverse social determinants of health associated with the rural population and these included a low income (P<0.0001), low education level (P<0.01), low insurance status (P<0.01), and treatment at a low-volume facility (P<0.0001). CONCLUSIONS: Rural/urban outcome disparities for resected stage I-III pancreatic cancer outcome can be explained by adverse social determinants of health associated with rural population.

Treatment at a high-volume academic research program mitigates racial disparities in pancreatic adenocarcinoma.

BACKGROUND: Racial disparities have long been a subject of concern between patients afflicted with pancreatic cancer in the United States. We believe that, in addition to a high-volume center, treatment at an academic research program (ARP) will mitigate racial outcome disparities. METHODS: A total of 12,950 patients diagnosed with stage I-III pancreatic adenocarcinoma from 2003-2011 and at ACS Commission on Cancer (COC) accredited facilities [e.g., high-volume (≥12 cases/year) ARPs] were evaluated from the National Cancer Data Base (NCDB). Sociodemographic, clinicopathological, and treatment variables were compared between Black (N=1,127) and White (N=11,823) patients. The Kaplan-Meier Estimator and Cox Proportional Hazards Model were used for survival analysis. P value ≤0.05 was considered significant. RESULTS: Black patients had a significantly higher overall survival (OS) than White patients, despite having a significantly lower household income, lower education level, more stage III disease, more Medicaid recipients, and higher comorbidity index (P<0.05). The 5-year unadjusted OS (28.6% versus 23.9%, a median survival time (months) was (25.2 versus 23.7 months for Black and White patients, respectively (P<0.05). There was no significant difference in surgical margin status or receipt of chemoradiation between the two cohorts. After adjusting for covariates, race was no longer a significant predictor of OS (P=0.096). CONCLUSIONS: Treatment at a high volume, ARP can mitigate racial disparities in pancreatic cancer.

Recent advances in the management of primary hepatic tumors refinement of surgical techniques and effect on outcome.

Advances in diagnostic, anesthetic, and surgical techniques have led to significant reductions in perioperative morbidity and mortality. The preoperative factors that have been of particular importance are a careful evaluation of hepatic function and of the predicted future liver remnant (FLR) volume prior to a decision on the feasibility of resection. Better patient selection, increased understanding of the liver anatomy leading to anatomical resections has together led to marked improvement in outcomes. In this article, we discuss the pre- and intraoperative factors, which have evolved in the last decade influencing the trend towards increased safety. We also share our technique of liver resection.

Regional treatment of colorectal liver metastasis.

Compared to systemic chemotherapy, intraarterial administration of tumoricidal agents with or without systemic chemotherapy in the treatment of nonresectable metastatic colorectal cancer is associated with superior response rate. The time-to-hepatic progression is also increased but the effect on overall survival is variable. When combined with other treatment modalities the number of patients who benefit from the treatment increases. In a subgroup of patients with resectable disease, hepatic artery infusion of chemotherapy as adjuvant therapy may be beneficial. Progression of the disease, hepatic and systemic toxicity, and complexity of the surgical aspects of the treatment limit the routine use of this treatment modality.

Thermoablation of colorectal liver metastasis.

Thermoablation is a local therapy that is effective in in situ destruction of colorectal liver metastasis while preserving surrounding normal liver tissue. It is less invasive compared to surgery, easy to use, and can be repeated. The therapy provides local control of unresectable disease and is an alternative therapy for small resectable lesions in patients with insufficient hepatic reserve after resection or coexistent comorbid conditions. It can artificially increase the resection margin thus increasing the number of patient candidate for resection. When used in conjunction with liver resection it clears the liver of multiple lesions that are surgically inaccessible or unresectable. Main limitations of the treatment are local recurrence of the disease, treatment-related complications, and questionable impact on patient. Outcome of therapy can be improved when used as part of multimodality treatment.

Co-expression of urokinase with haptoglobin in human carcinomas.

BACKGROUND: We have shown that colon and breast cancer contains large amounts of urokinase (uPA), and that these cells are the actual sites of its synthesis. We isolated a large complex molecule consisting of the beta-chain of uPA, both chains of haptoglobin (Hp), and part or all of an NCAM-like molecule. The question arose whether it would be possible to show the presence of Hp in the same cells where uPA was found. MATERIALS AND METHODS: Human colon and breast adenocarcinomas were investigated for expression of Hp and uPA by immunohistochemistry. Fluorescence in situ hybridization was used to identify the cells of origin of these antigens. RESULTS: Hp was expressed in 8 of 11 colon adenocarcinomas, and in 10 of 12 breast tumors. uPA was demonstrable on the cell membrane and in the cytoplasm of all 11 colon adenocarcinomas studied, and cytoplasmic uPA-mRNA was found in all cases. While uPA was also detected in some stromal and inflammatory cells, Hp was present abundantly in such cells, as well as in capillary endothelial cells. Hp-mRNA was also found in both colon and breast tumors wherever the antigens were expressed. CONCLUSIONS: uPA and Hp are produced by the cancer cells and are not taken up by stromal elements. While the role of uPA in the malignant process is well documented, that of Hp is largely unexplored. Its ubiquity, shown here, suggests that it is also involved in some aspects of that process.

Surgical resection after TNFerade therapy for locally advanced pancreatic cancer.

CONTEXT: Treatment of pancreatic cancer remains a major oncological challenge and survival is dismal. Most patients, present with advanced disease at diagnosis and are not candidates for curative resection. Preoperative chemoradiation may downstage and improve survival in locally advanced pancreatic cancer. This has prompted investigators to look for novel neoadjuvant therapies. Gene therapy for pancreatic cancer is a novel investigational approach that may have promise. TNFerade is a replication deficient adenovirus vector carrying the human tumor necrosis factor (TNF)-alpha gene regulated under control of a radiation-inducible gene promoter. Transfection of tumor cells with TNFerade maximizes the antitumor effect of TNF-alpha under influence of radiation leading to synergistic effects in preclinical studies. CASE REPORT: We describe a case of locally advanced unresectable pancreatic cancer treated with a novel multimodal approach utilizing gene therapy with TNFerade and concurrent chemoradiation that was followed by successful surgical resection. CONCLUSION: Neoadjuvant TNFerade based chemoradiation therapy may be a useful adjunct to treatment of locally advanced pancreatic cancer.

Synergism of CPT-11 and Apo2L/TRAIL against two differentially sensitive human colon tumor xenografts.

OBJECTIVE: The ability to sustain and grow portions of human tumors as xenografts in SCID mice provides a valuable preclinical opportunity to test the response of human tumors to treatments, both individually and in combination. Using this model, our laboratory has previously demonstrated that the growth of several human adenocarcinomas can be inhibited by Apo2L/TRAIL. Apo2L/TRAIL triggers apoptosis in many types of tumor cells, and when combined with various chemotherapeutic agents results in enhanced inhibition of tumor growth in many xenograft models. METHODS: To gain further insight into the antitumor potential of Apo2L/TRAIL in combination with chemotherapy, we compared the responses of 2 human colon adenocarcinomas, both of which were sensitive to CPT-11 while one was sensitive and the other comparatively resistant to Apo2L/TRAIL. RESULTS: In both cases, a greater degree of growth inhibition was achieved when these agents were used in combination. Western blot analysis demonstrated that in the Apo2L/TRAIL-sensitive tumor total cellular expression of Apo2L/TRAIL death receptors (DR4 and DR5) as well as protein expression of the pro-apoptotic molecule BAX were higher and the anti-apoptotic molecule Bcl-2 was lower in comparison to the Apo2L/TRAIL-resistant tumor. CONCLUSION: These results indicate that both Apo2L/TRAIL-sensitive and -resistant colon tumors will respond to a combination of CPT-11 and Apo2L/TRAIL and predict that this will be useful in the treatment of human colon cancers in a clinical setting.

Proinflammatory cytokines increase hepatocellular carcinoma cells thermotolerance: evidence of how local inflammation may negatively impact radiofrequency ablation local control rates.

BACKGROUND: Hepatocellular carcinomas (HCC) associated with inflammation that undergo radiofrequency ablation (RFA) appear to have poorer local control rates. Little is known of how mediators of inflammation influence HCC cellular thermotolerance, which in part is mediated by heat shock protein 70 (HSP70). This study determines how inflammatory mediators affect cellular thermotolerance and provides insight into how associated inflammation may impact HCC RFA local control rates. METHODS: HepG2 cell lines were cultured in control medium (CM) or CM containing conditioned medium of endotoxin-activated macrophage (CMM). Serial dilutions of CMM established microenvironments approximating low, medium, and high CMM. All groups underwent a heat shock challenge (HSC) at 45 degrees C for 10 min. Western blot, Northern blot, densitometric analysis, along with thymidine and clonogenic assays determined how inflammation influenced multiple biological endpoints. RESULTS: Cells cultured in low CMM expressed significantly more HSP70 RNA and protein compared with control cells after HSC. The cells also had a higher proliferative and survival rate after HSC compared with control cells. Medium CMM cultured cells had no significant difference in HSP70 RNA and protein production or proliferation and survival rates after HSC, compared with CM cultured cells. AT high CMM, the inhibitory effects of inflammatory mediators prevailed and all of the measured endpoints were significantly less compared with CM cultured cells. CONCLUSIONS: This study demonstrates that inflammation can alter the responsiveness of HCC cells to a HSC in a dose-dependent manner. This study supports the clinical observation that HCC associated with chronic inflammation have worse RFA local control rates.

Aberrant crypt foci as precursors in colorectal cancer progression.

Colorectal cancer progression originates when accumulated genetic and epigenetic alterations cause genomic instability and a malignant phenotype. Subsequent molecular pathway deregulation leads to histopathologic changes that are clinically evident as aberrant crypt foci (ACF) and visualized by high-magnification chromoscopic colonoscopy. ACF are biomarkers of increased colorectal cancer risk, particularly those with dysplastic features. Genetic profiling using genomic instability, loss of heterozygosity, and methylation analysis has revealed a minority population of ACF genotypically analogous to cancer.