Comparison of Clinical Breast Exam to Breast MRI Surveillance in Patients Following Nipple-Sparing Mastectomy.

BACKGROUND: Nipple sparing mastectomy (NSM) is increasingly being performed for patients with breast cancer. However, optimal postoperative surveillance has not been defined. METHODS: A prospectively maintained database identified patients with in-situ and invasive cancer who underwent NSM between 2007-2021. Clinical data on postoperative breast surveillance and interventions were collected. Patients who had MRI surveillance versus clinical breast exam (CBE) alone were compared with respect to tumor characteristics, recurrence, and survival. RESULTS: A total of 483 NSMs were performed on 399 patients. 255 (63.9%) patients had invasive ductal carcinoma, 31 (7.8%) invasive lobular carcinoma, 92 (23.1%) DCIS, 6 (1.5%) mixed ductal and lobular carcinoma, 9 (2.3%) others, and 6 (1.5%) unknown. Postoperatively, 265 (66.4%) patients were followed with CBE alone and 134 (33.6%) had surveillance MRIs. At a median follow-up of 33 months, 20 patients (5.0%) developed in-breast recurrence, 6 patients had (1.5%) an axillary recurrence, and 28 with (7.0%) distant recurrence. 14 (53.8%) LRR were detected in the CBE group and 12 (46.2%) were detected in the MRI group (P = .16). Overall survival (OS) was 99%, with no difference in OS between patients who had CBE alone versus MRI (P = .46). MRI was associated with higher biopsy rates compared to CBE alone (15.8% vs. 7.8%, P = .01). CONCLUSIONS: Compared to CBE alone, the use of screening MRI following NSM results in higher rate of biopsy and no difference in overall survival.

Gastric outlet obstruction caused by heterotopic pancreas in a patient with alcohol use disorder.

INTRODUCTION AND IMPORTANCE: Heterotopic Pancreas (HP) is defined by the presence of pancreatic tissue in an anatomically distinct location from the main pancreas. While often clinically silent, it may present symptomatically. If located in the gastric antrum, HP may cause gastric outlet obstruction (GOO). The objective of this paper is to present a rare case of HP in the gastric antrum causing GOO. CASE PRESENTATION: Herein, we report a 43-year-old man who presented with abdominal pain and non-bilious emesis in the setting of COVID-19 infection and alcohol consumption. During the initial workup, computed-tomography (CT) was non-specific but demonstrated GOO, concerning for cancer. Cold forceps biopsies taken during esophagogastroduodenoscopy (EGD) confirmed benign HP. Since the patient was symptomatic from gastric outlet compression, he underwent resection via laparoscopic distal gastrectomy and Billroth II gastrojejunostomy. At 1-month postoperative follow-up, the patient recovered uneventfully. We hypothesized that GOO by HP in this case may have been associated with cumulative effects of alcohol consumption and COVID-19 infection on the ectopic tissue. CLINICAL DISCUSSION: HP is rare and difficult to diagnose preoperatively. When located in gastric antrum, HP can cause GOO, mimicking gastric malignancy. Combination of EGD/EUS, biopsy/FNA, and surgical resection are necessary to definitively make the diagnosis. Finally, it is important to consider that heterotopic pancreatitis or structural changes in HP may occur due to classic pancreatic stressors like alcohol and viral infections. CONCLUSION: HP may cause GOO presenting with non-bilious emesis and abdominal pain, mistaken for malignancy on CT imaging.

Bronchoscopy-guided removal of intrabronchial coil migration after coil embolization of pulmonary arteriovenous malformation.

Pulmonary arteriovenous malformations develop in approximately 50% of hereditary hemorrhagic telangiectasia patients. Pulmonary arteriovenous malformations are often treated with coil embolization therapy. We report a case of a 45-year-old female with multiple pulmonary arteriovenous malformations due to underlying hereditary hemorrhagic telangiectasia who had undergone 14 coil embolization procedures over 16 years. She presented with sudden onset severe, unremitting, nonproductive cough from a foreign body sensation in the airway. Computed tomography of the chest demonstrated a metallic foreign body extending from the left lower lobe of the lung into the left mainstem bronchus and trachea. Bronchoscopy-guided removal of the foreign body revealed an intact embolization coil placed 8 years prior to presentation had partially migrated through the vessel and airway walls into the airway lumen, extending from the left lower lobe bronchus to the left mainstem bronchus. Coil migration is a rare, but potentially dangerous, complication of coil embolization therapy.

The Effect Modification of Ultrasound Risk Classification on Molecular Testing in Predicting the Risk of Malignancy in Cytologically Indeterminate Thyroid Nodules.

Background: Thyroid nodules with indeterminate cytology are increasingly subjected to molecular testing. We evaluated the diagnostic performances of Afirma Genomic Sequencing Classifier (GSC) and ThyroSeq v3 in thyroid nodules with high versus low/intermediate suspicion ultrasound classification. Methods: In this prospective cohort study, we analyzed all Bethesda III and IV thyroid nodules that underwent fine-needle aspiration biopsies in the University of California Los Angeles Health System from July 2017 to April 2020. All patients underwent molecular testing with Afirma GSC or ThyroSeq v3 as part of an institutional randomized trial (NCT02681328). Nodules were categorized according to the American Thyroid Association (ATA) ultrasound risk classification. The benign call rate and the positive predictive value of molecular testing were compared between ATA high suspicion versus all other categories. Results: A total of 343 patients with 375 indeterminate thyroid nodules were included. The malignancy rate in ATA high suspicion nodules was not significantly increased by a suspicious Afirma GSC result (77.8% for all ATA high suspicion nodules vs. 87.5% for nodules with ATA high suspicion and suspicious Afirma GSC results, positive likelihood ratio [LR] = 2.0, 95% confidence interval [CI 0.5-8.0], p = 1.0) or by a positive ThyroSeq v3 result (80.0% vs. 80.0%, positive LR = 1.0 [CI 1.0-1.0], p = 1.0). The rate of malignancy in ATA low/intermediate suspicion nodules increased from 21.0% to 56.3% with a suspicious Afirma GSC result (positive LR = 4.8 [CI 3.4-6.9], p < 0.0001) and decreased to 3.8% with a benign Afirma GSC result (negative LR = 0.1 [CI 0.07-0.3], p < 0.0001). Similarly, the rate of malignancy in ATA low/intermediate suspicion nodules increased from 24.3% to 66.7% with a positive ThyroSeq v3 result (positive LR = 6.2 [CI 4.0-9.7], p < 0.0001) and decreased to 2.1% with a negative ThyroSeq v3 result (negative LR = 0.07 [CI 0.02-0.3], p < 0.0001). Conclusions: Afirma GSC and ThyroSeq v3 performed well in ruling out malignancy in sonographically low/intermediate suspicion thyroid nodules but has limited diagnostic value in sonographically high suspicion nodules. Molecular testing can prognosticate more aggressive thyroid cancers, which can inform treatment decisions.

Short-term perioperative outcomes among patients with concurrent asymptomatic and mild SARS-CoV-2 infection: A retrospective, multicenter study.

BACKGROUND: Previous studies report high rates of postoperative morbidity and mortality among patients with SARS-CoV-2 (COVID-19). With routine preoperative screening, we are identifying an increasing number of patients with asymptomatic and mild COVID-19. Based on these prior studies, we hypothesized that patients with asymptomatic and mild COVID-19 infections have low perioperative morbidity and mortality. The purpose of this study was to determine the risk of perioperative morbidity and mortality associated with operations performed on patients diagnosed with asymptomatic or mild COVID-19. METHODS: A multicenter, retrospective study of patients with asymptomatic/mild SARS-CoV-2 (COVID-19) infection diagnosed within 8 days of surgery from March 2020 to February 2021. The primary outcome was 30-day mortality, and secondary outcomes included pulmonary complications and perioperative morbidity. The Chinese Center for Disease Control and Prevention criteria of COVID severity was used for categorization. RESULTS: The initial cohort included 53 patients. COVID-19 infection was detected preoperatively in 86.8%. At admission, 90.5% of patients were asymptomatic, 7.5% had mild COVID-19 symptoms, and 1.9% were unknown due to obtundation and later determined to be asymptomatic. Of the 53 cases, 35.8% were general surgical and 18.9% orthopedic; the remaining 54.7% were other surgical subspecialties. Overall mortality was 0%. New COVID-19 symptoms developed in 13.2% of patients postoperatively, with only 11.3% developing postoperative pulmonary complications. CONCLUSION: Postoperative morbidity and mortality rates were low among patients with asymptomatic and mild COVID-19. The risks of nonoperative management should be weighed against these operative risks in such patients with surgical indications.

Patient-Centered Decision-making for Postoperative Narcotic-Free Endocrine Surgery: A Randomized Clinical Trial.

Importance: Historically, opioid pain medications have been overprescribed following thyroid and parathyroid surgery. Many narcotic prescriptions are incompletely consumed, creating waste and opportunities for abuse. Objective: To determine whether limiting opioid prescriptions after outpatient thyroid and parathyroid surgery to patients who opt in to narcotic treatment reduces opioid consumption without increasing postoperative pain compared with usual care (routine narcotic prescriptions). Design, Setting, and Participants: A randomized clinical trial of Postoperative Opt-In Narcotic Treatment (POINT) or routine narcotic prescription (control) was conducted at a single tertiary referral center from June 1 to December 30, 2020. A total of 180 adults undergoing ambulatory cervical endocrine surgery, excluding patients currently receiving opioids, were assessed for eligibility. POINT patients received perioperative pain management counseling and were prescribed opioids only on patient request. Patients reported pain scores (0-10) and medication use through 7 daily postoperative surveys. Logistic regression was used to determine factors associated with opioid consumption. Interventions: Patients in the POINT group were able to opt in or out of receiving prescriptions for opioid pain medication on discharge. Control patients received routine opioid prescriptions on discharge. Main Outcomes and Measures: Daily peak pain score through postoperative day 7 was the primary outcome. Noninferiority was defined as a difference less than 2 on an 11-point numeric rating scale from 0 to 10. Analysis was conducted on the evaluable population. Results: Of the 180 patients assessed for eligibility, the final study cohort comprised 102 patients: 48 randomized to POINT and 54 to control. Of these, 79 patients (77.5%) were women and median age was 52 (interquartile range, 43-62) years. A total of 550 opioid tablets were prescribed to the control group, and 230 tablets were prescribed to the POINT group, in which 23 patients (47.9%) opted in for an opioid prescription. None who opted out subsequently required rescue opioids. In the first postoperative week, 17 POINT patients (35.4% of survey responders in the POINT group) reported consuming opioids compared with 27 (50.0%) control patients (P = .16). Median peak outpatient pain scores were 6 (interquartile range, 4-8) in the control group vs 6 (interquartile range, 5-7) in the POINT group (P = .71). In multivariate analysis, patients with a history of narcotic use were 7.5 times more likely to opt in (95% CI, 1.61-50.11; P = .02) and 4.8 times more likely to consume opioids (95% CI, 1.04-1.52; P = .01). Higher body mass index (odds ratio, 1.11; 95% CI, 1.01-1.23; P = .03) and highest inpatient postoperative pain score (odds ratio, 1.24; 95% CI, 1.04-1.52; P = .02) were also associated with opioid consumption. Conclusions and Relevance: In this trial, an opt-in strategy for postoperative narcotics reduced opioid prescription without increasing pain after cervical endocrine surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04710069.

Resolving mechanisms of immune-mediated disease in primary CD4 T cells.

Deriving mechanisms of immune-mediated disease from GWAS data remains a formidable challenge, with attempts to identify causal variants being frequently hampered by strong linkage disequilibrium. To determine whether causal variants could be identified from their functional effects, we adapted a massively parallel reporter assay for use in primary CD4 T cells, the cell type whose regulatory DNA is most enriched for immune-mediated disease SNPs. This enabled the effects of candidate SNPs to be examined in a relevant cellular context and generated testable hypotheses into disease mechanisms. To illustrate the power of this approach, we investigated a locus that has been linked to six immune-mediated diseases but cannot be fine-mapped. By studying the lead expression-modulating SNP, we uncovered an NF-κB-driven regulatory circuit which constrains T-cell activation through the dynamic formation of a super-enhancer that upregulates TNFAIP3 (A20), a key NF-κB inhibitor. In activated T cells, this feedback circuit is disrupted-and super-enhancer formation prevented-by the risk variant at the lead SNP, leading to unrestrained T-cell activation via a molecular mechanism that appears to broadly predispose to human autoimmunity.

MYC and Twist1 cooperate to drive metastasis by eliciting crosstalk between cancer and innate immunity.

Metastasis is a major cause of cancer mortality. We generated an autochthonous transgenic mouse model whereby conditional expression of MYC and Twist1 enables hepatocellular carcinoma (HCC) to metastasize in >90% of mice. MYC and Twist1 cooperate and their sustained expression is required to elicit a transcriptional program associated with the activation of innate immunity, through secretion of a cytokinome that elicits recruitment and polarization of tumor associated macrophages (TAMs). Systemic treatment with Ccl2 and Il13 induced MYC-HCCs to metastasize; whereas, blockade of Ccl2 and Il13 abrogated MYC/Twist1-HCC metastasis. Further, in 33 human cancers (n = 9502) MYC and TWIST1 predict poor survival (p=4.3×10-10), CCL2/IL13 expression (p<10-109) and TAM infiltration (p<10-96). Finally, in the plasma of patients with HCC (n = 25) but not cirrhosis (n = 10), CCL2 and IL13 were increased and IL13 predicted invasive tumors. Therefore, MYC and TWIST1 generally appear to cooperate in human cancer to elicit a cytokinome that enables metastasis through crosstalk between cancer and immune microenvironment.

Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation.

Cancer is a leading cause of death worldwide. Because the cytotoxic effects of conventional chemotherapies often harm normal tissue cells along with cancer cells, conventional chemotherapies cause many unwanted or intolerable side effects. Thus, there is an unmet medical need to establish a paradigm of chemotherapy-induced differentiation of cancer cells with tolerable side effects. Here we show that low-dose metformin or SN-38 inhibits cell growth or survival in ovarian and breast cancer cells and suppresses their tumor growth in vivo. Low-dose metformin or SN-38 increases FOXO3 nuclear localization as well as the amount of DNA damage markers and downregulates the expression of a cancer-stemness marker CD44 and other stemness markers, including Nanog, Oct-4, and c-Myc, in these cancer cells. This treatment also inhibits spheroid body-formation in 3-dimensional culture. In contrast, silencing FOXO3 diminishes all these cellular events when ovarian/breast cancer cells are treated with the mentioned drugs. These results suggest that low-dose metformin or SN-38 may reprogram these cancer cells into non-cancerous cells in a FOXO3-dependent manner, and may allow patients to overcome these cancers with minimal side effects.