Focus: A Multifaceted Battle Against Cancer: Nuns,Warts, Viruses,and Cancer

It has been known for more than 150 years that the risk of carcinoma of the uterine cervix correlates with the number of sexual partners. Laboratory and epidemiological evidence demonstrated that infection with certain human papillomavirus (HPV) types initiates the vast majority of, if not all, cervical cancer, as well as a substantial fraction of other cancers, including other anogenital cancer and oropharyngeal cancer. Pap smear testing resulted in a dramatic reduction in the incidence of cervical cancer in the developed world, and HPV vaccination has the potential to eradicate HPV-associated cancer worldwide and represents a major public health breakthrough. The major current challenge is to ensure that HPV vaccines are widely administered.     

Focus: A Multifaceted Battle Against Cancer: Approaches to Identifying Synthetic Lethal Interactions in Cancer

Targeting synthetic lethal interactions is a promising new therapeutic approach to exploit specific changes that occur within cancer cells. Multiple approaches to investigate these interactions have been developed and successfully implemented, including chemical, siRNA, shRNA, and CRISPR library screens. Genome-wide computational approaches, such as DAISY, also have been successful in predicting synthetic lethal interactions from both cancer cell lines and patient samples. Each approach has its advantages and disadvantages that need to be considered depending on the cancer type and its molecular alterations. This review discusses these approaches and examines case studies that highlight their use.     

Focus: A Multifaceted Battle Against Cancer: Gene-by-Environment Interactions in Pancreatic Cancer: Implications for Prevention

Pancreatic cancer (PC) has been estimated to have higher incidence and correspondingly higher mortality rates in more developed regions worldwide. Overall, the age-adjusted incidence rate is 4.9/10⁵ and age-adjusted mortality rate is at 4.8/10⁵. We review here our current knowledge of modifiable risk factors (cigarette smoking, obesity, diet, and alcohol) for PC, genetic variants implicated by genome-wide association studies, possible genetic interactions with risk factors, and prevention strategies to provide future research directions that may further our understanding of this complex disease. Cigarette smoking is consistently associated with a two-fold increased PC risk. PC associations with dietary intake have been largely inconsistent, with the potential exception of certain unsaturated fatty acids decreasing risk and well-done red meat or meat mutagens increasing risk. There is strong evidence to support that obesity (and related measures) increase risk of PC. Only the heaviest alcohol drinkers seem to be at an increased risk of PC. Currently, key prevention strategies include avoiding tobacco and excessive alcohol consumption and adopting a healthy lifestyle. Screening technologies and PC chemoprevention are likely to become more sophisticated, but may only apply to those at high risk. Risk stratification may be improved by taking into account gene environment interactions. Research on these modifiable risk factors is key to reducing the incidence of PC and understanding who in the population can be considered high risk.     

Focus: A Multifaceted Battle Against Cancer: The Cost of Cancer-Related Physician Services to Medicare

Although physician services represent a substantial portion of cancer care costs, little is known about trends in the costs of physician cancer services in the fee-for-service Medicare program. We analyzed aggregated data from all Part B Medicare claims for physician and supplier services attributed to cancer patients from 1999 to 2012 to characterize how billing and payments have changed over time for the most common cancer types. Billing and expenditure data are from the Medicare Statistical Supplement, and age-adjusted incidence data are from SEER. Physician services for cancer patients grew from $7.6 billion in 1999 to $12.3 billion in 2012 (60 percent increase). Reimbursements for physician and supplier services for cancer treatment in Medicare Part B beneficiaries steadily grew from 1999 to 2005 and then plateaued through 2012, led by a decrease in reimbursements for prostate cancer care. These trends may reflect shifts toward hospital-based care or changes in aggressiveness of care.     

Focus: A Multifaceted Battle Against Cancer: The Benefit and Burden of Cancer Screening in Li-Fraumeni Syndrome: A Case Report

Li-Fraumeni syndrome is a rare cancer predisposition syndrome classically associated with remarkably early onset of cancer in families with a typical spectrum of malignancies, including sarcoma, breast cancer, brain tumors, and adrenocortical carcinoma. Because the risks of cancer development are strikingly high for Li-Fraumeni syndrome, aggressive cancer surveillance is often pursued in these individuals. However, optimal screening methods and intervals for Li-Fraumeni syndrome have yet to be determined. In addition, there may be a significant psychosocial burden to intensive cancer surveillance and some prevention modalities. Here, we describe a case of a young woman with a de novo mutation in TP53 and multiple malignancies, with her most recent cancers found at early, curable stages due to aggressive cancer screening. The potential benefits and risks of intensive cancer surveillance in hereditary cancer syndromes is discussed.     

Focus: A Multifaceted Battle Against Cancer: Extracting Knowledge from Chemical Imaging Data Using Computational Algorithms for Digital Cancer Diagnosis

Fourier transform infrared (FTIR) spectroscopic imaging is an emerging microscopy modality for clinical histopathologic diagnoses as well as for biomedical research. Spectral data recorded in this modality are indicative of the underlying, spatially resolved biochemical composition but need computerized algorithms to digitally recognize and transform this information to a diagnostic tool to identify cancer or other physiologic conditions. Statistical pattern recognition forms the backbone of these recognition protocols and can be used for highly accurate results. Aided by biochemical correlations with normal and diseased states and the power of modern computer-aided pattern recognition, this approach is capable of combating many standing questions of traditional histology-based diagnosis models. For example, a simple diagnostic test can be developed to determine cell types in tissue. As a more advanced application, IR spectral data can be integrated with patient information to predict risk of cancer, providing a potential road to precision medicine and personalized care in cancer treatment. The IR imaging approach can be implemented to complement conventional diagnoses, as the samples remain unperturbed and are not destroyed. Despite high potential and utility of this approach, clinical implementation has not yet been achieved due to practical hurdles like speed of data acquisition and lack of optimized computational procedures for extracting clinically actionable information rapidly. The latter problem has been addressed by developing highly efficient ways to process IR imaging data but remains one that has considerable scope for progress. Here, we summarize the major issues and provide practical considerations in implementing a modified Bayesian classification protocol for digital molecular pathology. We hope to familiarize readers with analysis methods in IR imaging data and enable researchers to develop methods that can lead to the use of this promising technique for digital diagnosis of cancer.     

Focus: A Multifaceted Battle Against Cancer: Evolution of Multidisciplinary Brain Metastasis Management: Case Study and Literature Review

Up to 40 percent of all cancer patients develop brain metastasis (BM) during the course of their disease. Despite advances in diagnosis and therapy, prognosis in patients with BM remains poor for many patients, but for some, survival can be of the order of several years in duration. Difficulty in predicting long-term survivors has created controversy in contemporary management of BM. Minimizing medical and neurocognitive side effects (disease borne or iatrogenic) to enhance functional independence and improving overall quality of life in these individuals requires a coordinated approach of first-line and salvage surgical, chemotherapeutic (cytotoxic, targeted, or immune based), and radiation (whole brain radiotherapy or stereotactic radiosurgery) modalities. This goal needs to be balanced against the more traditional targets of management such as symptom relief, reducing tumor burden, and local tumor control, thereby increasing progression-free survival. This case study and literature review demonstrates the role of various treatment modalities in the management of BM.     

Focus: A Multifaceted Battle Against Cancer: Ashley W. Oughterson,MD: Surgeon,Soldier, Leader

Ashley W. Oughterson, MD, (1895-1956) was a longtime faculty surgeon at Yale University. He performed some of the earliest pancreatic resections in the United States. During World War II, Colonel Oughterson was the primary “Surgical Consultant” in the South Pacific and present at nearly every major battle. His meticulously kept diary is regarded as the foremost source detailing wartime surgical care. Colonel Oughterson led the initial Army team to survey Hiroshima and Nagasaki following the nuclear attacks. Thoughout his academic career at Yale, Oughterson was a key leader in several medical and surgical societies. As scientific director of the American Cancer Society, Oughterson lectured widely and guided research priorities in oncology following World War II. Oughterson also authored numerous benchmark papers in surgical oncology that continue to be cited today. These extensive contributions are examined here and demonstrate the wide-ranging impact Oughterson exerted during a formative period of American surgery.     

Focus: A Multifaceted Battle Against Cancer: Basal Cell Carcinoma: Pathogenesis,Epidemiology, Clinical Features,Diagnosis, Histopathology,and Management

Basal cell carcinoma (BCC) is the most common malignancy. Exposure to sunlight is the most important risk factor. Most, if not all, cases of BCC demonstrate overactive Hedgehog signaling. A variety of treatment modalities exist and are selected based on recurrence risk, importance of tissue preservation, patient preference, and extent of disease. The pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management of BCC will be discussed in this review.     

Kefir: A Multifaceted Fermented Dairy Product

Kefir is a fermented dairy beverage produced by the actions of the microflora encased in the “kefir grain” on the carbohydrates in the milk. Containing many bacterial species already known for their probiotic properties, it has long been popular in Eastern Europe for its purported health benefits, where it is routinely administered to patients in hospitals and recommended for infants and the infirm. It is beginning to gain a foothold in the USA as a healthy probiotic beverage, mostly as an artisanal beverage, home fermented from shared grains, but also recently as a commercial product commanding shelf space in retail establishments. This is similar to the status of yogurts in the 1970s when yogurt was the new healthy product. Scientific studies into these reported benefits are being conducted into these health benefits, many with promising results, though not all of the studies have been conclusive. Our review provides an overview of kefir’s structure, microbial profile, production, and probiotic properties. Our review also discusses alternative uses of kefir, kefir grains, and kefiran (the soluble polysaccharide produced by the organisms in kefir grains). Their utility in wound therapy, food additives, leavening agents, and other non-beverage uses is being studied with promising results.