Neoadjuvant Reirradiation for Radiation Therapy-Associated Angiosarcoma of the Breast.

PURPOSE: Radiation-associated angiosarcoma of the breast (RAASB) is a rare side effect after breast radiation and has been associated with poor outcomes. At this time, there is no consensus regarding management of RAASB, and the role of reirradiation remains controversial. We present our modern institutional outcomes in managing RAASB with incorporation of neoadjuvant hyperfractionated reirradiation. METHODS AND MATERIALS: Patients identified were treated between 2016 and 2020 with inclusion of any histologically proven RAASB without metastatic disease at diagnosis, while excluding those with a history of radiation therapy outside of the breast/chest wall or other sarcoma histologies. Major wound complications were defined as requiring wound care and/or wound vacuum or return to the operating room for wound repair at any time after surgery. RESULTS: Eight patients were identified, and the median follow-up was 34 months. Median time to RAASB development was 8 years from initial radiation therapy. With respect to RAASB management, all underwent surgery and neoadjuvant reirradiation therapy, and all but 1 patient received taxol-based chemotherapy. At last follow-up, 7 patients remained free of disease, and 1 patient died with distant disease. With respect to acute toxicity after reirradiation, all patients developed at least acute grade 2 toxicities. Five of the 8 patients developed a major wound complication. CONCLUSIONS: Our institutional analysis suggests excellent local control and survival outcomes for RAASB treated with neoadjuvant hyperfractionated reirradiation, surgery, and taxol-based chemotherapy. However, major wound complications represent a major challenge with this approach. Future studies should consider how best to improve the therapeutic ratio while maintaining high rates of local control and survival.

Five Fraction Accelerated Partial Breast Irradiation Versus Intraoperative Radiation Therapy for Early-Stage Breast Cancer.

PURPOSE/OBJECTIVE(S): Accelerated partial breast irradiation (PBI) delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable clinical outcomes to whole breast irradiation with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were promising, concerns exist regarding long-term rates of local recurrence after IORT. We present a comparison of 5 fraction PBI versus IORT. MATERIALS/METHODS: We performed a retrospective review of 473 patients with early-stage breast cancer treated at a single institution from 2011 to 2021 with 258 receiving PBI and 215 receiving IORT. PBI patients received 30 Gy in 5 fractions delivered with IMRT. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface at surgery using the low-energy TARGIT technique. RESULTS: Mean age was 71 years old (IQR:67-74) for IORT patients and 67 years old (IQR:62-72) for PBI patients. Median follow up was 5.7 years (IQR:4.2-7.0) for IORT patients and 2.4 years (IQR:1.8-3.3) for PBI patients (P < .001). Recurrence at any time (locoregional and distant) was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving PBI. IORT was associated with reduced rates of locoregional relapse free survival at 5 years (93.6% vs. 99.4%, P = .05) with no difference in overall survival(92.8% vs. 95.1%, P = .99). CONCLUSION: Low-energy TARGIT IORT was associated with higher rates of locoregional recurrence compared to PBI. These outcomes, consistent with other series and current guidelines, suggest a limited role for low-energy IORT as monotherapy.

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: Updated Outcomes from a Single-Institution Experience.

BACKGROUND: Increasingly, data have supported the use of partial-breast irradiation (PBI) for low-risk patients after breast-conserving surgery, with techniques allowing for completion of treatment in 1-3 weeks. Intraoperative radiation therapy (IORT) is an alternative to PBI. Our institution had used low-energy photon IORT (TARGIT) for more than a decade. The initial results demonstrated a 2% local recurrence rate with a short follow-up period of 2 years. This report presents updated outcomes during with 5-year follow-up. METHODS: A review of an institutional review board (IRB)-approved institutional registry was performed. The review identified 215 patients with early-stage breast cancer (stages 0-IIA) who received IORT. At the time of surgery, IORT was delivered with 20 Gy in a single fraction, with 5.1% (n = 11) of patients receiving additional whole-breast irradiation (WBI). RESULTS: The mean age at diagnosis was 71 years (range, 49-98 years), and the median follow-up was 5.7 years (interquartile range [IQR], 4.2-7.0 years). Of the 215 patients, 2.8% (n = 6) had ductal carcinoma in situ (DCIS), 90.7% (n = 195) had T1 disease, and 6.5% (n = 14) had T2 disease. Endocrine therapy was prescribed for 79% and chemotherapy for 1.4% of the patients. The 5-year rates were 5.3% for local recurrence, 6.4% for locoregional recurrence, and 2.7% for distant metastases. At 5 years, 93% of the patients were alive. CONCLUSIONS: The 5-year outcomes with TARGIT IORT demonstrated high rates of local recurrence, exceeding those seen with alternative modern approaches. The local recurrence outcomes with IORT are more consistent with studies omitting radiation following breast-conserving surgery, using endocrine therapy alone. Consistent with current guidelines and previous data, TARGIT IORT should not be used as monotherapy outside prospective clinical trials.

An Institutional Evaluation of Race and Ethnic Diversity in Pre-clerkship Lectures.

The goal of this project was to assess the current state of racial and ethnic presentation in medical pedagogy using the pre-clerkship curriculum at Case Western Reserve University School of Medicine (CWRU SOM). We systematically reviewed 20,630 slides across the basic sciences curriculum from 2020 to 2022 for references to race, ethnicity, or photos of people of color. Results showed that race and ethnicity are overwhelmingly used as biological constructs and references lack appropriate historical context. In addition, this project constructed learning objectives that provide suggestions to shift medical discourse on race and ethnicity from contemplation to a state of solution.

Update on Accelerated Whole Breast Irradiation.

Since the advent of breast conservation, adjuvant radiation therapy (RT) has been standard of care following breast conserving surgery (BCS). Radiation therapy following BCS has traditionally been whole breast irradiation (WBI); studies comparing breast conservation to mastectomy utilized standard fractionation WBI, which delivers treatment daily over 5 to 7 weeks (1.8-2 Gy/fraction) and was the standard for decades. More recently, multiple randomized trials have compared standard fractionation WBI to moderately hypofractionated WBI (2.66 Gy/fraction, 15-16 fractions), which allows for completion of treatment in 3 to 4 weeks. Results have demonstrated no difference in local control between these two approaches with comparable toxicity and cosmetic outcomes with long-term follow-up. As such, moderately hypofractionated WBI represents the standard of care approach for most patients with early-stage breast cancer following BCS at this time. In the past few years, ultra-hypofractionated WBI (5.2-5.7 Gy/fraction, 5 fractions) has emerged with promising outcomes; 5-year outcomes from the FAST-Forward randomized trial demonstrated noninferiority between ultra-hypofractionated WBI and moderately hypofractionated WBI. Moving forward, long-term outcomes from ultra-hypofractionated WBI studies are expected, as well as the potential for incorporating moderately hypofractionated regimens into patients requiring regional nodal irradiation following BCS. Finally, the advent of ultra-short regimens may allow clinicians to re-evaluate treatment de-intensification in early-stage breast cancer to consider radiation therapy alone following BCS in lieu of endocrine therapy.

Assessing the Impact of COVID-19 Phased Vaccine Eligibility on COVID-19 Vaccine Intent among African Americans in Southeastern Louisiana: A Community-Based, Cohort Study.

The purpose of this study was to explore the impact of eligibility for the coronavirus 2019 (COVID-19) vaccine at the time of the vaccine rollout as a predictor of vaccine intent within the African American community. METHODS: Four hundred eighty-seven African American participants in southeastern Louisiana were surveyed from January-April of 2021, with follow-up surveys occurring in Fall 2021. Survey domains included demographics, vaccine hesitancy, discrimination in the healthcare setting, and knowledge and experiences with COVID-19. Descriptive statistics, Chi-square tests, and binary logistic regression were performed. RESULTS: Participants eligible for the vaccine were 1.61 times as likely to express positive vaccine intent versus ineligible participants. Additional predictors of vaccine intent were age, insurance status and coverage, and female sex at birth. In the multivariable logistic analysis, eligible individuals were 2.07 times as likely to receive the vaccine versus ineligible individuals. CONCLUSIONS: Vaccine eligibility for the COVID-19 vaccine was a significant predictor of intent to vaccinate in the African American community. Younger individuals were less likely to have a positive intent, correlating with the eligibility of ages 16+ occurring 5 months post-vaccine approval.

ONS Guidelines™ to Support Patient Adherence to Oral Anticancer Medications.

PURPOSE: This evidence-based guideline intends to support patients, clinicians, and others regarding interventions and processes to support patient adherence to oral anticancer medications (OAMs). METHODOLOGIC APPROACH: A panel of healthcare professionals and patient representatives developed a clinical practice guideline to support patients taking OAMs. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology and criteria for trustworthy guidelines were followed. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. A quantitative or narrative synthesis of the evidence was completed. Certainty of the evidence was assessed using GRADE. FINDINGS: The panel agreed on recommendations and suggested an adherence risk assessment, education addressing adherence, ongoing assessment, proactive follow-up, coaching, and motivational interviewing in addition to usual care. The panel suggested the implementation of a structured OAM program. IMPLICATIONS FOR NURSING: As cancer treatment shifts from clinic to home settings, interventions and programs to support patients on OAMs are needed.

A novel fragmented mitochondrial genome in the protist pathogen Toxoplasma gondii and related tissue coccidia.

Mitochondrial genome content and structure vary widely across the eukaryotic tree of life, with protists displaying extreme examples. Apicomplexan and dinoflagellate protists have evolved highly reduced mitochondrial genome sequences, mtDNA, consisting of only three cytochrome genes and fragmented rRNA genes. Here, we report the independent evolution of fragmented cytochrome genes in Toxoplasma and related tissue coccidia and evolution of a novel genome architecture consisting minimally of 21 sequence blocks (SBs) totaling 5.9 kb that exist as nonrandom concatemers. Single-molecule Nanopore reads consisting entirely of SBs ranging from 0.1 to 23.6 kb reveal both whole and fragmented cytochrome genes. Full-length cytochrome transcripts including a divergent coxIII are detected. The topology of the mitochondrial genome remains an enigma. Analysis of a cob point mutation reveals that homoplasmy of SBs is maintained. Tissue coccidia are important pathogens of man and animals, and the mitochondrion represents an important therapeutic target. The mtDNA sequence has been elucidated, but a definitive genome architecture remains elusive.

Pancreatic volume does not correlate with histologic fibrosis in adult patients with recurrent acute and chronic pancreatitis.

OBJECTIVES: Reduced pancreatic volume, often referred to as atrophy, is a commonly reported imaging feature of chronic pancreatitis (CP). This study evaluated whether there is an association between pancreatic volume and fibrosis, the criterion standard of CP, in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT) for recurrent acute pancreatitis (RAP) and CP. METHODS: All adult patients who underwent TPIAT between 2010 and 2019 were categorized into 3 groups: RAP, definite CP and indeterminate CP. Pancreatic volume was calculated by summing up the areas from each thin section of the pancreas on 3D CT imaging. Excisional biopsies of the pancreatic head as well as body/tail region were obtained at the time of TPIAT. Two different fibrosis scores were used for histologic assessment. RESULTS: A total of 16, 29 and 15 patients underwent TPIAT for RAP, definite CP and indeterminate CP, respectively. The mean pancreatic volumes for patients with RAP, definite CP and indeterminate CP were 65.7 ± 28.5 cc, 54.9 ± 22.9 cc and 61.8 ± 23.6 cc, respectively (p = 0.3). The mean fibrosis scores were significantly higher in patients with definite CP compared to RAP (p < 0.001) and indeterminate CP (p < 0.001). Pancreatic volume was not associated with either fibrosis score after adjusting for age, gender, duration of disease, BMI and diabetes in the multivariable analysis. CONCLUSIONS: While the fibrosis scores were higher in definite CP compared to both RAP and indeterminate CP, there was no correlation between pancreatic volume and fibrosis. This suggests that atrophy alone cannot be used to diagnose CP.

Microbial Contamination, Infection, and Antimicrobial Use During Total Pancreatectomy With Islet Autotransplantation.

OBJECTIVES: Total pancreatectomy with islet autotransplantation can relieve pain associated with chronic pancreatitis while preserving islet function. Islet preparations are often contaminated by enteric flora. We assessed the impact of contaminated islet preparations on the prevalence of postoperative infection. METHODS: Electronic health records for patients who underwent total pancreatectomy with islet autotransplantation from August 1, 2011, to November 15, 2017 were retrospectively reviewed to compare the prevalence of postoperative infection in patients with a positive islet culture and islet culture negative patients. RESULTS: Sixty-one patients were included. Twenty-nine patients (47.5%) had a positive islet culture, and 23 (79.3%) of these patients received antimicrobial prophylaxis. The prevalence of postoperative infection did not differ between the islet culture positive and islet culture negative groups (41% vs 34%, P = 0.57). No infections occurred in the 6 islet culture positive patients who did not receive prophylaxis. No difference in intensive care unit or hospital length of stay or in 30-day or 90-day readmission rates were observed. CONCLUSIONS: Despite the common use of postoperative systemic antimicrobials, we observed no difference in the prevalence of postoperative infection, length of stay, or hospital readmission in patients receiving a contaminated islet preparation. If prophylactic antimicrobials are used, the duration should be minimized.

Glycemic Outcomes of Islet Autotransplantation.

PURPOSE OF REVIEW: While there has been a growing utilization of total pancreatectomy with islet autotransplantation (TPIAT) for patients with medically refractory chronic pancreatitis over the past few decades, there remains a lack of consensus clinical guidelines to inform the counseling and management of patients undergoing TPIAT. In this article, we review the current clinical practice and published experience of several TPIAT centers, outline key aspects in managing patients undergoing TPIAT, and discuss the glycemic outcomes of this procedure. RECENT FINDINGS: Aiming for lower inpatient glucose targets immediately after surgery (usually 100-120 mg/dl), maintaining all patients on subcutaneous insulin for at least 3 months to "rest" islets before an attempt is made to wean insulin, and close outpatient endocrinology follow-up after TPIAT particularly in the first year is common and related to better outcomes. Although TPIAT procedures and glycemic outcomes may differ across surgical centers, overall, approximately one third of patients are insulin independent at 1 year after TPIAT. Higher islet yield and lower preoperative glucose levels are among the strongest predictors of short-term post-operative insulin independence. Beyond 1 year post-operatively, the clinical management and long-term glycemic outcomes of patients after TPIAT are more variable. A multidisciplinary approach is essential in optimizing the preoperative, inpatient, and post-operative management and counseling of patients about the expected glycemic outcomes after surgery. Consensus guidelines for the clinical management of diabetes after TPIAT and harmonization of data collection protocols among TPIAT centers are needed to address the current knowledge gaps in clinical care and research and to optimize glycemic outcomes after TPIAT.

Prevalence and predictors of pain and opioid analgesic use following total pancreatectomy with islet autotransplantation for pancreatitis.

BACKGROUND & OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is employed for the management of refractory pain in chronic pancreatitis (CP) with the prospect of partial beta cell preservation. The primary aim of this study is to evaluate the prevalence and predictors of abdominal pain and opioid use following TPIAT. METHODS: A single center cohort study of all adult patients who underwent TPIAT from 2011 to 2015 for CP. Postoperative pain outcomes included: opioid use, ongoing abdominal pain and new characteristic abdominal pain. Multiple logistic regression analysis was used to evaluate known and potential predictors of postoperative pain outcomes. RESULTS: During the study period, 46 patients underwent TPIAT. Following surgery, 89% of patients had resolution of their pre-operative abdominal pain; however, 83% of patients developed a new characteristic abdominal pain. Opioid independence was achieved in 46% of patients. Acute recurrent pancreatitis (ARP) (OR: 11.66; 95%CI: 1.47-92.39; p = 0.02) but not pain duration >3 years or ≥ 5 ERCPs was independently associated with resolution of pre-operative abdominal pain on multiple logistic regression. None of these factors were associated with cessation of opioid use. CONCLUSION: While the majority of patients have resolution of their initial abdominal pain following TPIAT, many will also develop a new characteristic abdominal pain and only half of all patients achieve opioid independence. ARP is the only independent factor associated with positive postoperative pain outcomes and should be considered a standard criterion for patient selection.

Chronic Gastrointestinal Dysmotility and Pain Following Total Pancreatectomy with Islet Autotransplantation for Chronic Pancreatitis.

BACKGROUND: The prevalence and impact of chronic gastrointestinal dysmotility following total pancreactectomy with islet autotransplantation (TP-IAT) for chronic pancreatitis is not known. METHODS: A cross-sectional study of all patients who underwent TP-IAT at our institution from August 2011 to November 2015 was undertaken. The GCSI (Gastroparesis Cardinal Symptom Index), PAGI-SYM (Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index), PAC-SYM (Patient Assessment of Constipation Symptoms), Bristol stool chart, 12-item Short Form Health Survey (SF-12), and visual analog scale for pain were administered ≥4 weeks following TP-IAT. KEY RESULTS: The prevalence of any dysmotility symptoms in patients who completed the survey (33/45, 73%) post-TP-IAT was 45%. Post-TP-IAT, the mean reduction in opioid dosing was 77.6 oral morphine equivalents (OMEs) (95% CI 32.1-123.0, p = 0.002) with 42% of patients requiring no opioids. There was significant negative correlation between dysmotility scores and SF-12 physical scores (r = -0.46, p = 0.008, 95% CI -0.70 to -0.13). Self-reported abdominal pain had significant negative correlation with both physical and mental SF-12 scores (r = -0.67, p < 0.001, 95% CI -0.83 to -0.41 and r = -0.39, p = 0.03, 95% CI -0.65 to -0.04). There was no correlation between gastrointestinal dysmotility and self-reported pain. CONCLUSIONS AND INFERENCES: Symptoms of chronic gastrointestinal dysmotility and chronic abdominal pain are common post-TP-IAT and will need to be better recognized and differentiated to improve the management of these patients.

Glycemic Predictors of Insulin Independence After Total Pancreatectomy With Islet Autotransplantation.

CONTEXT: Total pancreatectomy with islet auto transplantation (TPIAT) is a treatment for medically refractory chronic pancreatitis that can prevent postsurgical diabetes in some patients. Predictors of insulin independence are needed for appropriate patient selection and counseling. OBJECTIVE: To explore glycemic predictors of insulin independence after TPIAT. DESIGN: A prospective cohort of patients. METHODS: We investigated 34 patients undergoing TPIAT from 2011-2016 at Johns Hopkins Hospital, all had a 75-g oral glucose tolerance test (OGTT) administered prior to their TPIAT. The primary outcome was insulin independence 1 year after TPIAT. RESULTS: Ten of 34 (29%) patients were insulin independent 1 year after TPIAT. All patients with impaired fasting glucose and/or impaired glucose tolerance preoperatively were insulin dependent at 1 year. In age-adjusted regression analyses, fasting glucose ≤ 90 mg/dL [odds ratio (OR) = 6.56; 1.11 to 38.91; P = 0.04], 1-hour OGTT glucose ≤ 143 mg/dL (OR = 6.65; 1.11 to 39.91; P = 0.04), and 2-hour OGTT glucose ≤ 106 mg/dL (OR = 11.74; 1.46 to 94.14; P = 0.02) were significant predictors of insulin independence. In receiver operating characteristic analyses, homeostatic model assessment of ß-cell function (HOMA-ß) was the most robust predictor of insulin independence [area under the curve (AUC) = 0.88; 0.73 to 1.00]. CONCLUSIONS: Normal preoperative glucose status and lower fasting and postchallenge OGTT glucose values are significant predictors of insulin independence after TPIAT. Higher islet function (HOMA-ß) was the strongest predictor. OGTT testing may be a useful tool to aid in patient counseling prior to TPIAT and should be further investigated.

Delayed Gastric Emptying (DGE) Following Total Pancreatectomy with Islet Auto Transplantation in Patients with Chronic Pancreatitis.

BACKGROUND: The prevalence and factors associated with delayed gastric emptying (DGE) in patients undergoing total pancreatectomy with islet auto transplantation (TP-IAT) for chronic pancreatitis are unknown. METHODS: A retrospective study of all patients who underwent TP-IAT at Johns Hopkins Hospital (JHH) from August 2011 to November 2014 was performed. The International Study Group of Pancreatic Surgery (ISGPS) clinical grading of DGE was used in this study. KEY RESULTS: A total of 39 patients with chronic pancreatitis underwent TP-IAT during the study period. The prevalence of DGE following TP-IAT was 35.9%. Twenty-five patients (64.1%) had no DGE, 10 (25.6%) had grade A, 2 (5.1%) had grade B, and 2 patients (5.1%) had grade C DGE. Patients with DGE had 5.7-fold higher odds of having a hospital length of stay (LOS) greater than 14 days (OR 5.70, 95% CI 1.37-23.76, p = 0.02). Patients undergoing laparoscopic TP-IAT had significantly shorter LOS (10.5 vs. 14 days, p = 0.02) and lower need for prokinetics (0.01) during the postoperative course. CONCLUSIONS AND INFERENCES: DGE is common after TP-IAT and can prolong LOS. Laparoscopic TP-IAT lowers LOS and need for prokinetics postoperatively. Further studies are needed to determine if laparoscopic approaches will improve long-term dysmotility.

Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First Results in Glioma Patients.

Recent animal studies have shown that D-glucose is a potential biodegradable MRI contrast agent for imaging glucose uptake in tumors. Here, we show the first translation of that use of D-glucose to human studies. Chemical exchange saturation transfer (CEST) MRI at a single frequency offset optimized for detection of hydroxyl protons in D-glucose (glucoCEST) was used to image dynamic signal changes in the human brain at 7T during and after infusion of D-glucose. Dynamic glucose-enhanced (DGE) image data from four normal volunteers and three glioma patients showed strong signal enhancement in blood vessels, while the enhancement varied spatially over the tumor. Areas of enhancement differed spatially between DGE and conventional Gd-enhanced imaging, suggesting complementary image information content for these two types of agents. In addition, different tumor areas enhanced with D-glucose at different times post-infusion, suggesting a sensitivity to perfusion-related properties such as substrate delivery and blood-brain barrier (BBB) permeability. These preliminary results suggest that DGE MRI is feasible to study glucose uptake in humans, providing a time-dependent set of data that contains information regarding arterial input function (AIF), tissue perfusion, glucose transport across the BBB and cell membrane, and glucose metabolism.

Focused glycomic analysis of the N-linked glycan biosynthetic pathway in ovarian cancer.

Epithelial ovarian cancer is the deadliest female reproductive tract malignancy in Western countries. Less than 25% of cases are diagnosed when the cancer is confined, however, pointing to the critical need for early diagnostics for ovarian cancer. Identifying the changes that occur in the glycome of ovarian cancer cells may provide an avenue to develop a new generation of potential biomarkers for early detection of this disease. We performed a glycotranscriptomic analysis of endometrioid ovarian carcinoma using human tissue, as well as a newly developed mouse model that mimics this disease. Our results show that the N-linked glycans expressed in both nondiseased mouse and human ovarian tissues are similar; moreover, malignant changes in the expression of N-linked glycans in both mouse and human endometrioid ovarian carcinoma are qualitatively similar. Lectin reactivity was used as a means for rapid validation of glycan structural changes in the carcinomas that were predicted by the glycotranscriptome analysis. Among several changes in glycan expression noted, the increase of bisected N-linked glycans and the transcripts of the enzyme responsible for its biosynthesis, GnT-III, was the most significant. This study provides evidence that glycotranscriptome analysis can be an important tool in identifying potential cancer biomarkers.