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.

     

Cancers et environnement : explorer les comportements de recherche et les sources d’information des personnes atteintes et non atteintes d’un cancer

Aim

To explore information-seeking behaviors on links between cancers and environment.

Method

Focus groups and individual semi-structured interviews realized, respectively, with individuals without and with personal cancer experience.

Results

The majority of respondents reported informationscanning behaviors. Only half cancer patients searched for information regarding the links between cancers and environment.

Conclusion

Little information is sought on links between cancers and environment.

     

Body image and psychological distress in women with breast cancer: a French online survey on patients’ perceptions and expectations

Background

Altered body image caused by alopecia, loss of eyebrows or eyelashes, or mastectomy is a major source of psychological distress in women with breast cancer.

Objective

To identify and to assess patients’ perceptions and expectations regarding altered body image.

Method

Opinion survey conducted among patients treated for breast cancer and member of French online support groups. Anonymous online self-administered survey sent to women with breast cancer.

Results

85% of the women interviewed experienced alopecia during treatment and 67% of them loss of eyebrows or eyelashes. About half of patients suffering alopecia and loss of eyebrows or eyelashes reported fearing what others think. Mastectomy was experienced by 84% of the women in our study, but only 32% of them reported fearing what others think. 87% of our study cohort received information about the possibility of adverse events. 70, 56, and 60% of women felt helped by information they received for the management of alopecia, loss of eyebrows or eyelashes, or mastectomy, respectively.

Conclusion

This study confirms that altered body image is a critical psychosocial issue for women with breast cancer. Effective information can be a source of reassurance and may constitute one of the most important sources of emotional support.

     

Metabolic syndrome and incidence of breast cancer in middle-aged Korean women: a nationwide cohort study

Purpose

To evaluate the risk of breast cancer in middle-aged women with metabolic syndrome using the National Health Insurance Service-National Sample Cohort (NHIS-NSC).

Methods

We analyzed 23,820 women aged 50–64 years who participated in the NHIS-NCS in 2008 and 2009. We excluded subjects with any previous history of cancer or with inadequate information regarding metabolic syndrome. Participated subjects underwent anthropometric measurements and provided fasting blood samples for the assessment of glucose and lipid profiles, and answered a lifestyle questionnaire. Cox regression analysis was performed to evaluate relative risks (RRs) and 95% confidence intervals (CIs) for the association between metabolic syndrome and breast cancer.

Results

During the 5-year follow-up, 131 subjects were newly diagnosed with breast cancer (incidence, 10.86 per 10,000 person years). After adjusting for age and body mass index, the RR for incident breast cancer in participants with metabolic syndrome versus those without it was 1.47 (95% CI 1.01–2.13). For those individuals of metabolic syndrome, hyperglycemia was most primarily related with the incidence of breast cancer (RR 1.44, 95% CI 1.02–2.04).

Conclusions

Among the study individuals who were middle-aged Korean women, metabolic syndrome is highly related with the risk of breast cancer. Therefore, it needs to be managed or prevented to reduce the incidence of breast cancer.

     

Mutation spectrum in South American Lynch syndrome families

Background

Genetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system.

Methods

We compiled data from publications and hereditary cancer registries to characterize the Lynch syndrome mutation spectrum in South America. In total, data from 267 families that fulfilled the Amsterdam criteria and/or the Bethesda guidelines from Argentina, Brazil, Chile, Colombia and Uruguay were included.

Results

Disease-predisposing mutations were identified in 37% of the families and affected MLH1 in 60% and MSH2 in 40%. Half of the mutations have not previously been reported and potential founder effects were identified in Brazil and in Colombia.

Conclusion

The South American Lynch syndrome mutation spectrum includes multiple new mutations, identifies potential founder effects and is useful for future development of genetic testing in this continent.

     

Obesity,Dietary Factors,Nutrition, and Breast Cancer Risk

Purpose of Review

To synthesize the critical role of obesity-associated inflammation, dietary factors, and nutrition in determining breast cancer risk.

Recent Findings

Obesity-associated inflammation is strongly linked to breast cancer risk and progression, largely via two processes: inflammatory pathways and dysregulated metabolism. Cytokine production in excess adipose tissues creates a chronic inflammatory microenvironment, which favors tumor development. Lifestyle factors, including diet, have long been recognized as important determinants of breast cancer risk and mortality.

Summary

Obesity increases the risk of developing breast cancer in both pre- and postmenopausal women and also negatively affects breast cancer recurrence and survival. Poor dietary habits characterized by the high intake of refined starches, sugar, and both saturated and trans-saturated fats, as well as the low intake of omega-3 fatty acids, natural antioxidants, and fiber, modulate inflammation and, thereby, appear to be linked to increased risk of breast cancer and mortality.

     

Preoperative biliary drainage-related inflammation is associated with shorter survival in biliary tract cancer patients

Background

An association between inflammation and patient prognosis has been reported in various types of cancer. The aim of this study was to evaluate the influence of preoperative biliary drainage-related inflammation in patients with biliary tract cancer.

Methods

The clinical data of 97 patients who underwent surgery for extrahepatic bile duct cancer between February 2002 and September 2014 were analyzed, and the prognostic significance of tube-obstructive cholangitis after preoperative biliary drainage and pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) was evaluated.

Results

Eighty-four (86.6 %) of the 97 patients underwent ERCP and preoperative biliary drainage. Tube-obstructive cholangitis occurred in 25 cases and post-ERCP pancreatitis in 8 cases. Collectively, 30 patients experienced preoperative biliary drainage-related inflammation consisting of tube-obstructive cholangitis and/or post-ERCP pancreatitis. Drainage-related inflammation was significant risk factor of postoperative complications (P = 0.006), and significant poor predictors of shorter progression-free survival (P = 0.003) and overall survival (OS; P = 0.006) after surgery. In multivariate analysis, drainage-related inflammation was an independent predictor of shorter OS (hazard ratio, 1.924; P = 0.037) after surgery.

Conclusion

Preoperative biliary drainage-related inflammation was an independent prognostic factor for shorter OS in biliary tract cancer patients.

     

Immunotherapy in Breast Cancer: the New Frontier

Purpose of review

This review summarizes current immunotherapies in breast cancer, with an emphasis on immune checkpoint inhibitors and vaccines.

Recent findings

Combination immunotherapy with checkpoint inhibitors and cytotoxic therapies have shown promising results. Active clinical trials are ongoing in both early stage and metastatic settings for triple negative, HER2+, and hormone-positive breast cancer patients.

Summary

Ongoing challenges remain in defining biomarkers that predict response to immunotherapy, determining the optimal combination immunotherapies, and enhancing the immunogenicity of breast cancer subtypes.

     

A prospective study of autoantibodies to Ezrin and pancreatic cancer risk

Purpose

No biomarker is available for pancreatic cancer early detection, but a small prospective European study involving 16 cases and 32 controls raised the possibility that anti-Ezrin autoantibodies may be associated with risk of pancreatic cancer. We aimed to validate this finding in a case–control study nested within a prospective study in the USA.

Methods

Levels of anti-Ezrin autoantibodies were examined using ELISA in pre-diagnostic plasma samples of 73 cases and 145 matched controls. Paired t test and paired signed rank tests were used to determine the difference between two groups, and conditional logistic regression was used to evaluate the association between anti-Ezrin autoantibody levels and risk of developing pancreatic cancer.

Results

No association was found between levels of anti-Ezrin plasma autoantibodies and subsequent risk of developing pancreatic cancer.

Conclusion

Anti-Ezrin autoantibodies did not appear to be useful as a plasma biomarker for early detection of pancreatic cancer.

     

A risk prediction model to allow personalized screening for cervical cancer

Importance

Cervical cancer screening guidelines are in evolution. Current guidelines do not differentiate recommendations based on individual patient risk.

Objective

To derive and validate a tool for predicting individualized probability of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) at a single time point, based on demographic factors and medical history.

Design

The study design consisted of an observational cohort with hierarchical generalized linear regression modeling.

Setting

The study was conducted in a setting of 33 primary care practices from 2004 to 2010.

Participants

The participants of the study were women aged ≥?30 years.

Main outcome and measures

CIN2+ was the main outcome on biopsy, and the following predictors were included: age, race, marital status, insurance type, smoking history, median income based on zip code, prior human papilloma virus (HPV) results.

Results

The final dataset included 99,319 women. Of these, 745 (0.75%) had CIN2+. The multivariable model had a C-statistic of 0.81. All factors but race were independently associated with CIN2+. The model categorized women as having below-average CIN2+ risk (0.15% predicted vs. 0.12% observed risk), average CIN2+ risk (0.42% predicted vs. 0.36% observed), and above-average CIN2+ risk (1.76% predicted vs. 1.85% observed). Before screening, women at below-average risk had a risk of CIN2+ well below that of women with ASCUS and HPV negative (0.12 vs. 0.20%).

Conclusions and relevance

A multivariable model using data from the electronic health record was able to stratify women across a 50-fold gradient of risk for CIN2+. After further validation, use of a similar model could enable more targeted cervical cancer screening.

     

Bone-Modifying Agents in Early-Stage and Advanced Breast Cancer

Purpose of Review

Bone-modifying agents have an important role in the treatment of patients with bone mineral density loss, early-stage breast cancer to reduce risk of recurrence, and metastatic breast cancer with bone involvement. Here we review mechanisms of action of these agents and clinical indications for their use.

Recent Findings

The meta-analysis undertaken by the Early Breast Cancer Trialists’ Collaborative Group showed that the use of bisphosphonates was associated with a decreased risk of breast cancer recurrence.

Summary

The effect of bisphosphonates and receptor activator of nuclear factor kappa-B ligand inhibitors on bone health provides an opportunity to decrease the incidence of skeletal-related events and improve cancer outcomes in certain subsets of patients.

     

Mechanisms of Neurotoxic Symptoms as a Result of Breast Cancer and Its Treatment: Considerations on the Contribution of Stress,Inflammation, and Cellular Bioenergetics

Purpose of Review

Breast cancer and its treatment are associated with a range of neurotoxic symptoms, such as fatigue, cognitive impairment, and pain. Although these symptoms generally subside after treatment completion, they become chronic in a significant subset of patients. We here summarize recent findings on neuroinflammation, stress, and mitochondrial dysfunction as mechanistic pathways leading to neurotoxic symptom experience in breast cancer patients and survivors.

Recent Findings

Neuroinflammation related to stress or cancer treatment and stress resulting from diagnosis, treatment, or (cancer-related) worrying are important predictors of a neurotoxic symptom experience, both during and after treatment for breast cancer. Both inflammation and stress hormones, as well as cancer treatment, can induce mitochondrial dysfunction resulting in reduced cellular energy.

Summary

We propose reduced cellular energy (mitochondrial dysfunction) induced by inflammation, oxygen radical production, and stress as a result of cancer and/or cancer treatment as a final mechanism underlying neurotoxic symptoms.

     

Wo ist die molekulare Pathologie sinnvoll?

Background

The increasing importance of molecular pathology in routine oncological diagnostics.

Objective

Current recommendations, developments and future applications of molecular pathology in the clinical course of malignant melanoma, colorectal cancer and non-small cell lung cancer (NSCLC).

Material and methods

The article is based on a literature review investigating clinically relevant aspects of molecular diagnostics in various databases, e.g. PubMed, the European Society of Medical Oncology (ESMO) and the World Health Organization (WHO).

Results and conclusion

The translation of preclinical research and the application in clinical practice are characterized by an increasing speed. The advanced classification of malignant diseases is of high relevance in current therapeutic approaches.

     

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.

     

Adolescent diet and risk of breast cancer

Background

Early life exposures, including diet, have been implicated in the etiology of breast cancer.

Methods

A nested case-control study was conducted among participants in the Nurses' Health Study who completed a 24-item questionnaire about diet during high school. There were 843 eligible cases diagnosed between onset of study (1976) and before the return of the high school diet questionnaire (1986), who were matched 10:1 with controls on the basis of age.

Results

Women who had, during adolescence, a higher consumption of eggs, vegetable fat and fiber had a lower risk of breast cancer, whereas risk of breast cancer was increased among women who consumed more butter.

Conclusions

A possible association of elements of adolescent diet with risk of breast cancer is reported, but the findings require confirmation in prospective study.

     

A population-based audit of ethnicity and breast cancer risk in one general practice catchment area in North London,UK: implications for practice

Objectives

To conduct a pilot population-based study within a general practice catchment area to determine whether the incidence of breast cancer was increased in the Ashkenazi population.

Design

Population-based cohort study.

Setting

A single general practice catchment area in North London.

Participants

1947 women over the age of 16 who responded to a questionnaire about ethnicity and breast cancer.

Main outcome measures

Incidence of breast cancer, ethnicity.

Results

This study showed a 1.5-fold (95% CI 0.93–2.39) increase in breast cancer risk in the Ashkenazim compared with the non-Ashkenazi white population. The increased incidence was for both premenopausal and postmenopausal breast cancer (expected incidence pre:post is 1:4 whereas in the Ashkenazim it was 1:1; 51 and 52% of cases respectively). This increase was not shown in the Sephardim. Asians had a reduction in incidence (OR = 0.44; 95% CI 0.10–1.89). Results were adjusted for other risk factors for breast cancer.

Conclusion

This study showed a 1.5-fold increase in breast cancer rates in Ashkenazim compared with the non-Jewish white population when adjusted for age (i.e. corrections were made to allow comparison of age groups) and this is not observed in the Sephardic population. The proportion of premenopausal breast cancer was just over double that of the general population. This is the first general practice population-based study in the UK to address this issue and has implications for general practitioners who care for patients from the Ashkenazi community.

     

Ernährung bei operativen Maßnahmen

Background

The special metabolic risk for complications must be taken into account in cancer patients undergoing extensive operations.

Method

This selective review of the literature refers to recent German S3 guideline recommendations.

Results

Early detection and observation of patients with weight loss and diminished food intake before hospital admission remain an essential part of perioperative management. With the aim of enhanced recovery after surgery (ERAS) and the reduction of postoperative morbidity there is a need for appropriate perioperative nutritional and metabolic care.

Conclusion

Whenever possible artificial nutritional support should be avoided; however, if inadequate oral intake has to be anticipated (> 10 days) in patients at risk nutritional support should be started early via the enteral route, maybe in combination with parenteral nutrition. Long-term total parenteral nutrition is restricted to special indications.

     

Sexual function in adolescents and young adults diagnosed with cancer: A systematic review

Purpose

The purpose of this systematic review was to identify, with supporting evidence, the impact of cancer and its treatment on the sexual function of adolescents and young adults.

Methods

PubMed, CINAHL, and PsycINFO articles were searched for relevant studies published in English. Fifteen studies, 13 quantitative and two qualitative, were included in this review.

Results

Results indicated that cancer during the adolescent and young adult period has a significant negative impact on certain domains of sexual function in both men and women.

Conclusions

Among adolescent and young adult males, there is evidence that cancer has detrimental effects on erection, ejaculation, and orgasm. Among adolescent and young adult females, cancer is associated with decreased desire, but there appear to be mixed findings with respect to arousal, orgasm, and satisfaction. Directions for future research are discussed.

Implications for Cancer Survivors

A better understanding of the effects of cancer and its treatment during adolescence and young adulthood on sexual function could increase attention paid to sexual health in oncology settings and lead to improved psychosexual services for this population.

     

Le burn-out des soignants travaillant en soins palliatifs

Background

The study was conducted in a sample of caregivers working in palliative care. We first examined the prevalence of the burnout syndrome in our sample through the assessment of emotional exhaustion, cynicism, and personal accomplishment. We also considered individuals’ factors to potentially explain caregivers’ burnout.

Method

Data were collected among a sample of 129 caregivers (doctors, nurses, auxiliary nurses) using four questionnaires: IPC (locus of control), PSS4 (perceived stress), WCC-R (coping strategies), and MBI (burnout).

Results

The study shows that 32.5% of the caregivers suffer from a burnout syndrome, especially with low levels of personal accomplishment. Moreover, the three components of the burnout syndrome are differentially related to individuals’ locus of control, perceived stress, and coping.

Conclusion

These results light on the importance of personal accomplishment in the work domain and have practical implications to enhance it.

     

Chirurgische Therapie des Magenkarzinoms

Background

Gastric cancer is one of the few tumor entities with a decreasing incidence but still constitutes a main cause of cancer-related deaths worldwide. The gold standard in therapy regimes with curative intent is surgery; however, palliative regimes should also include surgery in selected cases. Minimally invasive techniques are becoming established leading to improved perioperative outcomes.

Objective

Review of current oncological standards with a focus on the surgical approach in gastric cancer patients, discussion of current controversies regarding surgery with curative and palliative intent and outcomes of minimally invasive techniques.

Material and methods

Review of the literature on surgery of gastric cancer including conventional and minimally invasive tecnhniques.

Results

Surgery is the gold standard in regimes with curative intent for gastric cancer patients. The histological subtype is the basis for decision-making with respect to the extent of gastric resection. Radical D2 lymphadenectomy is the current standard in western countries. Multivisceral resection for locally advanced cancer is worthwhile in selected patients in terms of improved long-term survival despite potentially higher morbidity rates.. In palliative settings surgery can be a tool to improve the quality of life and to control tumor-related complications

Conclusion

Minimally invasive techniques are one of the main technical options to improve the perioperative outcome in gastric cancer patients. Multimodal therapy regimes may improve the quality of life and survival in curative and palliative settings.