Ultrasound for the Objective Measurement of Breast Lymphedema.

OBJECTIVES: Breast lymphedema has supplanted upper extremity lymphedema as a common and debilitating sequela of breast cancer treatment, but has no objective measurement. We assessed the utility of ultrasound-measured difference in dermal thickness between affected and unaffected breasts as a measure of breast lymphedema. We associated this measure with patient characteristics, treatment parameters, and patient-reported impact on quality of life. METHODS: We enrolled 30 invasive breast carcinoma patients treated with breast-conserving surgery, sentinel lymph node biopsy, and radiotherapy, and 10 control patients evaluated for benign breast conditions without prior breast surgery or radiotherapy. Patient and treatment variables were ascertained from medical records and radiotherapy instruments. Impacts on quality of life were measured with a modified Disability of the Arm, Shoulder, and Hand questionnaire. We characterized breast lymphedema by calculating the difference in ultrasound-measured dermal thickness between affected and unaffected breasts. Associations with patient characteristics, treatment, and quality of life were quantified with log-binomial regression models. RESULTS: Breast lymphedema was defined as a dermal thickness difference of >0.3 mm. Nineteen patients in the invasive group (63%) had breast lymphedema by this definition. We observed positive associations between ultrasound-defined breast lymphedema and surgical factors (size of primary tumor, number of lymph nodes removed), radiotherapy factors (breast volume irradiated, receipt of radiation boost), and patient-reported outcomes (sleep quality and overall confidence). CONCLUSIONS: Difference in dermal thickness is an easy and inexpensive measurement for quantifying breast lymphedema, and correlates with treatment parameters and patient-reported impacts on quality of life.

Gradual adoption of needle biopsy for breast lesions in a rural state.

BACKGROUND: Minimally invasive breast biopsy (MIBB) is the standard of care for the diagnosis of breast cancer, with consensus guidelines suggesting MIBB goals of 90% of total biopsies. In a previous study of patients in the rural state of Vermont, USA (population size of 640,000), rural breast cancer patients had open biopsies 42% of the time compared to 29% of urban breast cancer patients. The aim of this study was to assess overall population-based biopsy trends in Vermont. METHODS: The Vermont Breast Cancer Surveillance System (VBCSS) was used to identify women receiving MIBB and excisional breast biopsies in Vermont. Patient zip code at the time of initial biopsy was used to determine the patient residence rurality by rural-urban commuting area codes (RUCA 2.0™). RESULTS: There were 9122 diagnostic episodes from 1999 to 2018. MIBB was the initial biopsy method in 7524 (82.5%) cases, while surgical excision was the initial biopsy method in 1598 (17.5%) cases. A linear trend fit estimated an increase of 1.3% per year (p < 0.001, 95% CI 1.1%-1.5%) in the fraction of patients undergoing MIBB. Patients living in rural areas were less likely to receive MIBB (78.5%) than those living in urban areas (94.9%), p < 0.001. Multivariate analysis showed that urban patients and those patients in the years 2014-2018 were more likely to receive MIBB (OR 5.00, 95% CI 4.13-6.05 [p < 0.05] and OR 4.41, 95%CI 3.68-5.28 [p < 0.05], respectively). The rate of MIBB for rural patients increased and met the 90% quality standard in 2013 and ultimately matched urban patient rates of MIBB in 2018. CONCLUSIONS: For the first time, we show that MIBB usage is above 90% in the state of Vermont and that there no longer exist disparities in breast biopsies between urban and rural patients or rural/urban facilities in the state, overall.

Prokinetic actions of luminally acting 5-HT4 receptor agonists.

BACKGROUND: 5-HT4 receptor (5-HT4 R) agonists exert prokinetic actions in the GI tract, but non-selective actions and potential for stimulation of non-target 5-HT4 Rs have limited their use. Since 5-HT4 Rs are expressed in the colonic epithelium and their stimulation accelerates colonic propulsion in vitro, we tested whether luminally acting 5-HT4 R agonists promote intestinal motility. METHODS: Non-absorbed 5-HT4 R agonists, based on prucalopride and naronapride, were assessed for potency at the 5-HT4 R in vitro, and for tissue and serum distribution in vivo in mice. In vivo assessment of prokinetic potential included whole gut transit, colonic motility, fecal output, and fecal water content. Colonic motility was also studied ex vivo in mice treated in vivo. Immunofluorescence was used to evaluate receptor distribution in human intestinal mucosa. KEY RESULTS: Pharmacological screening demonstrated selectivity and potency of test agonists for 5-HT4 R. Bioavailability studies showed negligible serum detection. Gavage of agonists caused faster whole gut transit and colonic motility, increased fecal output, and elevated fecal water content. Prokinetic actions were blocked by a 5-HT4 R antagonist and were not detected in 5-HT4 R knockout mice. Agonist administration promoted motility in models of constipation. Evaluation of motility patterns ex vivo revealed enhanced contractility in the middle and distal colon. Immunoreactivity for 5-HT4 R is present in the epithelial layer of the human small and large intestines. CONCLUSIONS AND INFERENCES: These findings demonstrated that stimulation of epithelial 5-HT4 Rs can potentiate propulsive motility and support the concept that mucosal 5-HT4 Rs could represent a safe and effective therapeutic target for the treatment of constipation.