Early stage colon cancer: Current treatment standards, evolving paradigms, and future directions.

Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies. The majority of patients with colon cancer are diagnosed at an early stage (stages I to III), which provides an opportunity for cure. The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients, which is directed at the eradication of minimal residual disease to achieve a cure. Surgery alone is curative for the vast majority of colon cancer patients. Currently, surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement. Adjuvant chemotherapy is recommended for all patients with stage III colon cancer, while the benefit in stage II patients is not unequivocally established despite several large clinical trials. Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques, strategies to limit treatment-related toxicities, precise patient selection for adjuvant therapy, utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology. In this review, we will discuss the current standard treatment, evolving treatment paradigms, and the emerging biomarkers, that will likely help improve patient selection and personalization of therapy leading to superior outcomes.

Propranolol inhibits molecular risk markers in HCT recipients: a phase 2 randomized controlled biomarker trial.

Preclinical research shows that stress-induced activation of the sympathetic nervous system can promote hematopoietic malignancies via ß-adrenoreceptor-mediated molecular pathways. Hematopoietic cell transplant (HCT) recipients exposed to conditions of chronic stress show activation of a conserved transcriptional response to adversity (CTRA) gene expression profile, which in turn is associated with increased relapse and decreased disease-free survival. We conducted a randomized controlled phase 2 biomarker trial testing the impact of the nonselective ß-antagonist propranolol on CTRA-related gene expression of 25 individuals receiving an autologous HCT for multiple myeloma. Propranolol was administered for 1 week prior to and 4 weeks following HCT. Blood was collected at baseline, day -2, and day +28. Intention-to-treat analyses controlling for demographic characteristics, high-risk disease (International Myeloma Working Group risk score), and tumor stage tested effects on a 53-gene CTRA indicator profile and measures of CTRA-related cellular processes in peripheral blood mononuclear cells. Twelve participants were randomized to the intervention and 13 to the control. Relative to the control group, propranolol-treated patients showed greater decreases from baseline to HCT day -2 and day +28 for both CTRA gene expression (P = .017) and bioinformatic measures of CD16- classical monocyte activation (P = .005). Propranolol-treated patients also showed relative upregulation of CD34+ cell-associated gene transcripts (P = .011) and relative downregulation of myeloid progenitor-containing CD33+ cell-associated gene transcripts (P = .001). Ancillary analyses identified nonsignificant trends toward accelerated engraftment and reduced posttransplant infections in propranolol-treated patients. Peri-HCT propranolol inhibits cellular and molecular pathways associated with adverse outcomes. Changes in these pathways make propranolol a potential candidate for adjunctive therapy in cancer-related HCT.

Measurement of circulating tumor DNA to guide management of patients with lymphoma.

In recent years, advances have been made in methods to assess response to therapy in lymphoma. Ideally, response assessment tools should be highly sensitive and specific for identifying a disease, should carry a minimal risk of harm to the patient, and should provide reproducible results. Traditional surveillance methods have included clinical assessment and, in many cases, routine surveillance imaging. Minimal residual disease (MRD) refers to the detection of disease level below that of these traditional surveillance methods. Either circulating tumor cells or their nucleic acid fragments released from necrotic/apoptotic cells can be measured in circulating peripheral blood, referred to as circulating tumor DNA (ctDNA). ctDNA can be detected with allele-specific polymerase chain reaction (ASO-PCR) or with next-generation sequencing (NGS) techniques. The use of ctDNA as a monitoring strategy in lymphoma can aid in assessment of disease burden, as well as prognostication, customization of therapy ("risk-adapted" strategies), monitoring for relapse, and consideration of early intervention ("preemptive" strategies), while reducing radiation exposure from surveillance imaging modalities that are presently used. In this review, we discuss the current state of the art in ctDNA measurement, as well as the clinical data supporting its potential utility in the management of lymphoma patients.

We Are Caregivers: Social Identity Is Associated with Lower Perceived Stress among Rural Informal Caregivers.

ABSTRACTInformal caregivers often experience high stress levels with little support, especially in rural settings. With a mixed-methods approach, this research explored experiences of rural informal caregivers, including how social identification as a caregiver, social interactions, and formal and informal coping support related to perceived stress. Major focus group themes (n = 8) included lacking available services, balancing challenges, unmet practical needs, and strong community identity. Survey data (n = 22) revealed that perceived coping support (e.g., having someone to turn to), social interactions, and caregiver identity (e.g., perceiving the role as important to one's self-concept) were associated with lower life upset stress, but only caregiver identity was associated with managing the personal distress and negative feelings associated with caregiving stress. Results suggest that, although available rural services may fall short, other options might alleviate caregiver stress, including facilitating access to coping support, encouraging social interactions, and enhancing caregiver social identity.

Rasmussen's encephalitis: A case report.

Rasmussen's encephalitis (RE) is a rare neurological disorder of inflammatory aetiology characterised by encephalitis, intractable seizures, hemiparesis, variable motor deficits, and dementia. It is not commonly considered in the clinical differential diagnosis of a patient with a past history of a stroke-like episode presenting with status epilepticus. It is suspected mainly in children in whom the disease is more common. Here we report a case of an adult man presenting with a common symptom of seizure caused by Rasmussen's encephalitis.