Validation of self-reported comorbidity status of breast cancer patients with medical records: the California Breast Cancer Survivorship Consortium (CBCSC)

Purpose

To compare information from self-report and electronic medical records for four common comorbidities (diabetes, hypertension, myocardial infarction, and other heart diseases).

Methods

We pooled data from two multiethnic studies (one case–control and one survivor cohort) enrolling 1,936 women diagnosed with breast cancer, who were members of Kaiser Permanente Northern California.

Results

Concordance varied by comorbidity; kappa values ranged from 0.50 for other heart diseases to 0.87 for diabetes. Sensitivities for comorbidities from self-report versus medical record were similar for racial/ethnic minorities and non-Hispanic Whites, and did not vary by age, neighborhood socioeconomic status, or education. Women with a longer history of comorbidity or who took medications for the comorbidity were more likely to report the condition. Hazard ratios for all-cause mortality were not consistently affected by source of comorbidity information; the hazard ratio was lower for diabetes, but higher for the other comorbidities when medical record versus self-report was used. Model fit was better when the medical record versus self-reported data were used.

Conclusions

Comorbidities are increasingly recognized to influence the survival of patients with breast or other cancers. Potential effects of misclassification of comorbidity status should be considered in the interpretation of research results.

     

Personalizing Colon Cancer Screening: Role of Age and Comorbid Conditions

Purpose of Review

This review will discuss the impact of patient age and comorbidity on colorectal cancer (CRC) screening value.

Recent Findings

Society guidelines recommend CRC screening starting at age 50 in average-risk individuals, but there is less agreement about when screening should be discontinued. In clinical practice, CRC screening and follow-up recommendations among elderly patients appear to be driven more by chronological age than by comorbid illnesses. However, several studies have highlighted the interaction between age and comorbidity burden when selecting appropriate patients for CRC screening. Although CRC screening may be beneficial until age 75–80 years among patients with no comorbidity, it has only modest benefits at an early age in those with high comorbidity.

Summary

Clinicians should adopt the concept of “health-adjusted age” and identify “healthy elderly” patients who would benefit from CRC screening and the “unhealthy young” in whom the benefits of CRC screening are likely limited.

     

Lifestyle after Colorectal Cancer Diagnosis in Relation to Survival and Recurrence: A Review of the Literature

Purpose of Review

This review summarizes the evidence regarding diet, physical activity, smoking, and body composition after colorectal cancer (CRC) diagnosis in relation to all-cause and CRC-specific mortality and disease recurrence and gives suggestions for future research directions.

Recent Findings

Overall, this review suggests that some, albeit not all, of the well-known modifiable risk factors for cancer incidence might also be associated with CRC survival. CRC prognosis appears to be worse with increased physical inactivity, smoking, or being underweight after CRC diagnosis. Emerging evidence suggests that diets associated with a positive energy balance, e.g., high consumption of sugar-sweetened beverages, may negatively impact survival in CRC survivors. In contrast, there is currently little evidence to support the recommendation to limit red and processed meat or alcohol intake after CRC diagnosis. Whether being overweight and obese after CRC diagnosis improves or worsens CRC prognosis remains controversial and may depend on the measure used to assess body fatness.

Summary

Further research on post-diagnosis lifestyle patterns is needed to understand the multifactorial influence on CRC prognosis. Disease recurrence and the development of comorbidities should be included as key outcomes in future studies and lifestyle should preferably be repeatedly measured.

     

Resistance Mechanisms to Colorectal Cancer Therapeutics and the Clinical Implications

Purpose of Review

Colorectal cancer (CRC) is a leading cause of cancer-related death and additional treatment options are urgently needed. Cytotoxic chemotherapy has been the mainstay of treatment options for patients for many years, including FOLFOX (leucovorin, 5-fluorouracil (5-FU), and oxaliplatin) or FOLFIRI (5-FU, leucovorin, and irinotecan) Here we review the current clinical use of systemic therapies for metastatic CRC and mechanisms of resistance to these agents.

Recent Findings

Biologic therapies, including anti-angiogenic and anti-epidermal growth factor monoclonal antibodies, have shown increased efficacy for patients with metastatic CRC. Most recently, immunotherapies have also been an option for some patients.

Summary

Identification of molecular markers predictive of response or resistance has led to enhanced ability to treat patients with metastatic CRC in a more personalized fashion.

     

Clinical Factors as a Component of the Personalized Treatment Approach to Advanced Pancreatic Cancer: a Systematic Literature Review

Introduction

Pancreatic cancer is often diagnosed at late stages, where disease is either locally advanced unresectable or metastatic. Despite advances, long-term survival is relatively non-existent.

Discussion

This review article discusses clinical factors commonly encountered in practice that should be incorporated into the decision-making process to optimize patient outcomes, including performance status, nutrition and cachexia, pain, psychological distress, medical comorbidities, advanced age, and treatment selection.

Conclusion

Identification and optimization of these clinical factors could make a meaningful impact on the patient’s quality of life.

     

MicroRNA-33b inhibits tumor cell growth and is associated with prognosis in colorectal cancer patients

Purpose

To explore the role of miR-33b in colorectal cancer (CRC) and the correlation between its expression and prognosis.

Methods

The expressions of miR-33b between CRC tissues and normal tissues were measured by real-time PCR. The effects of miR-33b on cell proliferation and cell cycle progression were detected by MTT assay, colony formation assay and flow cytometry. The potential regulations of miR-33b on multiple genes expression were verified by Western blot. Furthermore, the association of miR-33b with CRC clinicopathologic features and prognosis was analyzed by Chi-squared test and Kaplan–Meier tests.

Results

MiR-33b was downregulated in CRC compared with normal colorectal samples and miR-33b inhibited tumor cell growth and induced cell cycle arrest. Western blot assays and correlation analysis showed that miR-33b could regulate multiple growth-related genes. Moreover, the expression of miR-33b was associated with TNM stage and tumor size, and CRC patients with high miR-33b expression had a better prognosis.

Conclusion

Our data suggest that miR-33b functions as a tumor suppressor gene in CRC through regulating cell proliferation and cell cycle.

     

Inflammation and Colorectal Cancer

Purpose of Review

Colorectal cancer (CRC) is the fourth most common cancer in both men and women in the USA, resulting in over 55,000 deaths annually. Environmental and genetic factors influence the development of CRC, and inflammation is a critical hallmark of cancer that may arise from a variety of factors. While patients with inflammatory bowel disease (IBD) have a higher risk of developing CRC, sporadic CRCs may engender or be potentiated by inflammation as well. In this review, we focus on recent advances in basic and translational research utilizing murine models to understand the contribution of inflammatory signaling pathways to CRC.

Recent Findings

We discuss advances in the utility of three-dimensional enteroid/colonoid/tumoroid cultures to understand immune-epithelial interactions in CRC, as well as the potential for utilizing patient-derived tumoroids for personalized therapies.

Summary

This review underscores the importance of understanding the complex molecular mechanisms underlying inflammation in sporadic CRC and highlights up-and-coming or new avenues for CRC biomarkers or therapies.

     

Physiological expression of pancreatic somatostatin receptors in 99mTc-HYNIC-TOC scintigraphy

Purpose

To describe the frequency of head and/or pancreas uncinate process uptake of 99mTc-HYNIC-TOC, to study its nature, and analyze its diagnostic value.

Materials and methods

Retrospective evaluation of 47 consecutive 99mTc-HYNIC-TOC examinations was conducted. Head and/or pancreas uncinate process uptake was considered to be physiological in patients with normal CT at the same episode and in follow-up. It was analyzed if age or diabetes mellitus was justifying the existence or not of uptake.

Results

32.5% patients showed uptake; 73% of them were mild. 84.6% patients with uptake have no pathology and 4% had neuroendocrine pancreatic disease at CT. Neither the age nor the diabetes mellitus established differences in patients without lesion.

Conclusions

Near one-third of patients show physiological uptake by head and/or pancreas uncinate process at 99mTc-HYNIC-TOC scintigraphy. It seems that neither the diabetes nor the ages are factors that determine this physiological uptake.

     

Plasma lipopolysaccharide-binding protein and colorectal cancer risk: a nested case–control study in the Multiethnic Cohort

Background

Lipopolysaccharide (LPS), an endotoxin found on the outer cell wall of Gram-negative bacteria, increases inflammatory response signaling and may play a role in the pathogenesis of several adverse outcomes, including inflammatory bowel diseases, cardiovascular disease, and cancer. While LPS is hypothesized to be associated with colorectal carcinogenesis, there are relatively few human studies which have examined this association.

Methods

We examined the association between colorectal cancer (CRC) and plasma lipopolysaccharide-binding protein (LBP), a marker of LPS, in 1,638 participants (819 CRC cases and 819 controls) matched on multiple factors, including age, sex, and race/ethnicity, from the Multiethnic Cohort study. Conditional logistic regression models were used to estimate the multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95% CI).

Results

Compared to individuals whose LBP concentrations were in the lowest quartile, the ORs associated with second, third, and fourth quartiles were 1.23 (95% CI 0.91–1.67), 1.36 (95% CI 1.01–1.83), and 1.01 (95% CI 0.73–1.39), respectively, (p _trend?=?0.66). No differences were observed by BMI, fiber intake, saturated fat intake, cancer site, or cancer stage.

Conclusions

This study did not find an overall statistically significant association between LBP (as a marker of LPS exposure) and CRC. Further prospective studies with multiple LBP measurements are needed to validate current findings.

     

Möglichkeiten der lokal-ablativen Bestrahlung (SBRT) bei metastasiertem kolorektalem Karzinom

Background

Colorectal cancer (CRC) often presents as oligometastatic disease. Currently available intensive systemic treatment regimens, including combination chemotherapy and molecular targeted agents, result in tumor response and transient to long-term disease control in a high percentage of patients, thus raising the question of further management. Secondary resection and ablation, e.g. by surgery or radiofrequency may contribute to long-term survival and even be curative or at least allow a relevant chemotherapy-free interval. These approaches are often limited by the anatomical site, invasiveness and morbidity of the respective procedure. With stereotactic body radiotherapy (SBRT) metastases can be treated with very high efficiency in only a few sessions and achieving long-term control.

Objectives

Identification of clinical studies investigating the use of SBRT for treatment of oligometastases in CRC patients. Control rates in liver and lung metastases and survival after SBRT. Toxicity and side effects of the treatment.

Material and methods

A literature search was carried out for prospective and retrospective studies on local SBRT.

Results and conclusion

The SBRT procedure has become a valid treatment option for patients with oligometastatic CRC and should also be considered in clinical practice as an alternative to surgical treatment of metastases or other local ablative techniques.

     

Analysis of gallstone disease after gastric cancer surgery

Background

The incidence rate of newly developed gallstone disease after gastrectomy for gastric cancer is thought to be higher than that in the general population. However, the presentation and management of these gallstones remain under debate, and the role of prophylactic cholecystectomy remains questionable.

Methods

Data on adult patients who were diagnosed with gastric cancer and received gastrectomy between 2000 and 2011 were extracted from the Taiwan National Health Insurance Research Database. A patient was excluded if he or she had gallstone disease or received cholecystectomy before the index date. The incidence of newly developed gallstone disease and its subsequent management were recorded. Data were analyzed to evaluate the factors associated with gallstone development and treatment options.

Results

A total of 17,325 gastric cancer patients who underwent gastrectomy were eligible for analysis. During the follow-up period (mean 4.1 years; median, 2.9 years), 1280 (7.4%) patients developed gallstone disease and 560 (3.2%) patients subsequently underwent cholecystectomy. The in-hospital mortality for cholecystectomy was 1.8% (10/560). Development of gallstone disease was associated with older age, total gastrectomy, duodenal exclusion, diabetes, cirrhosis, and more comorbidities. Factors associated with the use of cholecystectomy to treat gallstone disease included younger age, fewer comorbidities, medical center admission, and presentation as cholecystitis.

Conclusions

Although few patients required further gallbladder removal after gastrectomy for gastric malignancy, the increased mortality rate for subsequent cholecystectomy was worth noting. The decision to undergo prophylactic cholecystectomy might be individualized based upon patient characteristics and the surgeon’s discretion.

     

Racial differences in the effects of comorbidity on breast cancer-specific survival

Purpose

In an effort to explain racial disparities in breast cancer survival, this study aimed to investigate how comorbidity affects breast cancer-specific mortality by race.

Methods

A retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results—Medicare linked data including 68,090 women 66+ years, who were diagnosed with stage I–III breast cancer in the United States from 1994 to 2004. Hospital and outpatient claims from the year prior to breast cancer diagnosis were used to identify comorbid conditions and patients were followed for survival through 2010.

Results

Competing risk survival analysis failed to demonstrate any negative comorbidity effects on breast cancer-specific survival for black women. An increased breast cancer-specific mortality hazard was observed for white women who had diabetes without complication relative to white women without this condition after adjusting for age and year of diagnosis (hazard ratio: 1.22, 95% confidence interval 1.13, 1.30). The Cochran–Armitage Test showed diabetes was associated with a later stage of diagnosis (p < 0.01) and a more aggressive tumor grade (p < 0.01) among white women in the study population.

Conclusion

Race specific comorbidity effects do not explain breast cancer-specific survival disparities. However, the relationship between diabetes and breast cancer, including the role of aggressive tumor characteristics, warrants special attention.

     

Overexpression of forkhead box protein M1 (FOXM1) plays a critical role in colorectal cancer

Background

The forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas. However, the clinical significance of FOXM1 signaling in human colorectal cancer (CRC) pathogenesis remains unknown. The aim of this study was to evaluate the role of FOXM1 in CRC tumorigenesis.

Methods

We investigated FOXM1 expression in 103 cases of primary CRC and matched normal tissue specimens and explored the underlying mechanisms of altered FOXM1 expression and the impact of this altered expression on CRC proliferation and metastasis using in vitro models of CRC.

Results

The results showed that high expression of FOXM1 staining was 85.44 % (88/103) in 103 cases of CRC and 20.39 % (21/103) in 103 cases of adjacent non-cancerous tissue samples; the difference of FOXM1 expression between two groups was statistically significant (P < 0.001). Silencing of FOXM1 inhibited the proliferation of CRC cells, and the invasion and migration of CRC cells were distinctly suppressed. Furthermore, FOXM1 knockdown led to substantial reductions in VEGF-A levels in CRC cell lines.

Conclusions

Our data suggest that the pathogenesis of CRC maybe mediated by FOXM1, and FOXM1 could represent selective targets for the molecularly targeted treatments of CRC.

     

Are long-term cancer survivors and physicians discussing health promotion and healthy behaviors?

Purpose

This study aimed to (1) describe the proportion of survivors reporting that a physician discussed strategies to improve health and (2) identify which groups are more likely to report these discussions.

Methods

Lung cancer and colorectal cancer (CRC) survivors (>5 years from diagnosis) (n?=?874) completed questionnaires, including questions on whether, in the previous year, a physician discussed (1) strategies to improve health, (2) exercise, and (3) diet habits. Chi-square tests and logistic regression models were used to examine whether the likelihood of these discussions varied by demographic and clinical characteristics.

Results

Fifty-nine percent reported that a physician discussed strategies to improve health and exercise, 44 % reported discussions on diet, and 24 % reported no discussions. Compared to their counterparts, survivors with lower education were less likely to report discussing all three areas, but survivors with diabetes were more likely. Survivors ≥65 years old were less likely to report discussing strategies to improve health and diet. Males and CRC survivors reported discussing diet more than their female and lung cancer counterparts, respectively.

Conclusion

The frequency of health promotion discussions varied across survivor characteristics. Discussions were more frequently reported by some groups, e.g., survivors with diabetes, or among individuals less likely to engage in healthy behaviors. In contrast, males and older and less educated survivors were less likely to have these discussions.

Implications for Cancer Survivors

Decreasing physician barriers and encouraging patients to discuss health promotion, especially in the context of clinical care for older survivors and those with low education, is essential for promoting the overall well-being of cancer survivors.

     

Descending thoracic aortic aneurysm revealing metastasis of a soft tissue fibrosarcoma: a case report and review of the literature

Background

Review of the first documented case of aortic wall metastasis from a limb sarcoma.

Case presentation

In a 56-year-old woman with a diagnosis of a high-grade limb fibrosarcoma, an aortic metastasis was revealed by a fast growing aneurysm of the descending thoracic aorta. This was managed with an endoprosthesis.

Conclusion

The presence of an aneurysm in a patient with a sarcoma with a high potential for metastasis and poor cardiovascular risk factors should alert physicians.

     

What Is the Future of Circulating Tumor Cells in Colorectal Cancer?

Purpose of Review

To introduce recent progress on circulating tumor cell (CTC) research in colorectal cancer (CRC) and to highlight clinical application of CTCs from detection to assessment of treatment response.

Recent Findings

CTC biological characteristics in CRC play an important role in the detection of CTCs. The in vitro culture of CTCs from CRC patients (cell lines and organoids) can potentially facilitate rapid drug testing and treatment prediction. CTC detection should be standardized with improved detection rate in CRC; further, clinical investigation is still needed to clarify its potential as a tool for early CRC detection, a predictive and prognostic marker to ultimately guide treatment.

Summary

Gaining an improved understanding of CTCs characteristics and ultimately, integration of CTC detection and utilization of CTCs may lead to optimized tumor treatment and facilitate precision medicine.

     

Quality Colorectal Cancer Screening: Endoscopic Performance Measures and Beyond

Purpose of Review

The rationale behind and implementation of quality measures around colonoscopy for colorectal (CRC) screening are important topics for endoscopists to understand to deliver exemplary care with the goal of decreasing the incidence of this disease. This article will evaluate recent data on this subject and summarize pertinent findings in the growing field of quality improvement research surrounding colonoscopy for CRC screening.

Recent Findings

Both pre- and intra-procedural metrics have been studied across a variety of practice models and patient populations. Contemporary metrics include adequate bowel preparation, cecal intubation rate, adenoma detection rate, polypectomy rate, proximal serrated polyp detection rate, withdrawal time, and patient satisfaction.

Summary

Multiple quality metrics have been formally evaluated regarding colonoscopy, and others have recently been proposed. Additional validation is necessary to determine which quality metrics serve as practical and implementable to improve endoscopic performance and overall delivery of care.