Back to Basics: History and Physical Examination Uncover Colonic Metastasis in a Patient With Remote History of Breast Cancer.

We present the cast of a 74-year-old woman with a remote history of recurrent localized breast cancer who presented with nonspecific gastrointestinal symptoms who was subsequently found to have metastatic breast cancer in the transverse colon. Nonspecific gastrointestinal complaints can be the first sign of cancer recurrence in these patients. Providers should maintain a high index of suspicion for disease recurrence when evaluating cancer survivors.

Novel combination therapy for melanoma induces apoptosis via a gap junction positive feedback mechanism.

Metastatic melanoma cells overexpressing gap junctions were assayed for their ability to propagate cell death by a novel combination therapy that generates reactive oxygen species (ROS) by both 1) non-thermal plasma (NTP) and 2) tirapazamine (TPZ) under hypoxic conditions. Results demonstrate additive-to-synergistic effects of combination therapy compared to each agent individually. NTP induces highly localized cell death in target areas whereas TPZ partially reduces viability over the total surface area. However, when high gap junction expression was induced in melanoma cells, effects of combination NTP+TPZ therapy was augmented, spreading cell death across the entire plate. Similarly, in vivo studies of human metastatic melanoma in a mouse tumor model demonstrate that the combined effect of NTP+TPZ causes a 90% reduction in tumor volume, specifically in the model expressing gap junctions. Treatment with NTP+TPZ increases gene expression in the apoptotic pathway and oxidative stress while decreasing genes related to cell migration. Immune response was also elicited through differential regulation of cytokines and chemokines, suggesting potential for this therapy to induce a cytotoxic immune response with fewer side effects than current therapies. Interestingly, the gap junction protein, Cx26 was upregulated following treatment with NTP+TPZ and these gap junctions were shown to maintain functionality during the onset of treatment. Therefore, we propose that gap junctions both increase the efficacy of NTP+TPZ and perpetuate a positive feedback mechanism of gap junction expression and tumoricidal activity. Our unique approach to ROS induction in tumor cells with NTP+TPZ shows potential as a novel cancer treatment.

Safety and efficacy of sofosbuvir/velpatasvir/voxilaprevir in post-liver transplant patients with previous direct-acting antiviral failure: Six case reports.

BACKGROUND: Direct-acting antiviral (DAA) therapy regimens are highly effective at eliminating hepatitis C virus (HCV) infection but rates of sustained virologic response (SVR) are lower in patients with decompensated cirrhosis or hepatocellular carcinoma. Since many of these patients will be referred for liver transplant, they will require retreatment after transplantation. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is recommended by guidelines as the preferred regimen to treat HCV in DAA-experienced patients following liver transplant however there is limited data. CASE SUMMARY: We present the cases of six liver transplant recipients who had previous treatment failure with sofosbuvir-based DAA therapy prior to transplantation and who then received SOF/VEL/VOX after transplant. CONCLUSION: This case series demonstrate the real-world efficacy and safety of SOF/VEL/VOX in the post liver transplant setting. Treatment was successful with all patients achieving SVR, it was well tolerated, and there were minimal drug-drug interactions with their immunosuppressants.

Drug-Induced Liver Injury: Highlights of the Recent Literature.

Drug-induced liver injury (DILI), herbal-induced liver injury, and herbal and dietary supplement (HDS)-induced liver injury are an important aspect of drug safety. Knowledge regarding responsible drugs, mechanisms, risk factors, and the diagnostic tools to detect liver injury have continued to grow in the past year. This review highlights what we considered the most significant publications from among more than 1800 articles relating to liver injury from medications, herbal products, and dietary supplements in 2017 and 2018. The US Drug-Induced Liver Injury Network (DILIN) prospective study highlighted several areas of ongoing study, including the potential utility of human leukocyte antigens and microRNAs as DILI risk factors and new data on racial differences, the role of alcohol consumption, factors associated with prognosis, and updates on the clinical signatures of autoimmune DILI, thiopurines, and HDS agents. Novel data were also generated from the Spanish and Latin American DILI registries as well as from Chinese and Korean case series. A few new agents causing DILI were added to the growing list in the past 2 years, including sodium-glucose co-transporter-2 inhibitors, as were new aspects of chemotherapy-associated liver injury. A number of cases reported previously described hepatotoxins confirmed via the Roussel Uclaf Causality Assessment Method (RUCAM; e.g., norethisterone, methylprednisolone, glatiramer acetate) and/or the DILIN method (e.g., celecoxib, dimethyl fumarate). Additionally, much work centered on elucidating the pathophysiology of DILI, including the importance of bile salt export pumps and immune-mediated mechanisms. Finally, it must be noted that, while hundreds of new studies described DILI in 2017-2018, the quality of such reports must always be addressed. Björnsson reminds us to remain very critical of the data when addressing the future utility of a study, which is why it is so important to adhere to a standardized method such as RUCAM when determining DILI causality. While drug-induced hepatotoxicity remains a diagnosis of exclusion, the diverse array of publications that appeared in 2017 and 2018 provided important advances in our understanding of DILI, paving the way for our improved ability to make a more definitive diagnosis and risk assessment.

Smoking-related genitourinary cancers: A global call to action in smoking cessation.

Smoking is a known modifiable risk factor in the development of genitourinary malignancies. Although the association has long been supported by numerous research studies, the impact of smoking cessation on the decreased risk of genitourinary malignancies is less well studied. PubMed databases were searched using the terms smoking, smoking cessation, bladder cancer, kidney cancer, prostate cancer, penile cancer, testicular cancer, their synonyms, and also targeted manual searches to perform a literature review in order to summarize the benefits of cessation on disease progression and patient outcomes including survival and morbidities. Our review yielded substantial evidence highlighting the improved outcomes observed in those diagnosed with bladder, renal, and prostate cancers. The risk of bladder cancer is reduced by up to 60% in those who were able to quit for 25 years and the risk of kidney malignancy was reduced by 50% in those who abstained from smoking for 30 years. A similar trend of reduced risk was observed for prostate cancer with those who quit for more than 10 years, having prostate cancer mortality risks similar to those that never smoked. Although the data were encouraging for bladder, renal, and prostate malignancies, there are comparatively limited data quantifying the benefits of smoking cessation for penile and testicular cancers, highlighting an opportunity for further study. The role of urologists and their impact on their patients' likelihood to quit smoking shows more than half of urologists never discuss smoking cessation upon diagnosis of a malignancy. Most urologists said they did not provide cessation counseling because they do not believe it would alter their patients' disease progression. Studies show urologists have more influence at changing their patients' smoking behaviors than their primary care physicians. The diagnosis of cancer may lead to a teachable moment resulting in increased smoking quit rates. Furthermore, implementing a brief 5-minute clinic counseling session increases quit attempts and quit rates. Diagnosis of genitourinary cancers and the following appointments for treatment provide a unique opportunity for urologists to intervene and affect the progression and outcome of disease.