Clinical Outcomes Using Magnetic Seeds as a Non-wire, Non-radioactive Alternative for Localization of Non-palpable Breast Lesions.

BACKGROUND: Nonpalpable breast lesions require precise preoperative localization to facilitate negative margins with breast-conserving therapy. The traditional use of wires has several challenges including patient discomfort, wire migration, and coordination of schedules between radiology and the operating room. Radioactive seed localization overcomes some of these challenges, but radiation safety requirements have limited adoption of this technology. The authors examined their institutional experience with Magseed as an alternative technology for localization and compared outcomes with those of wire and radioactive seed localization. METHODS: An institutional review board (IRB)-approved retrospective study was performed to evaluate patients who underwent excisional biopsy or segmental mastectomy after wire-guided localization (WGL), radioactive seed localization (RSL), or Magseed localization (ML). The clinical and pathologic factors of the three groups were assessed with a negative margin rate as the primary outcome measure. RESULTS: Of the 1835 patients in the study, 825 underwent WGL, 449 underwent RSL, and 561 underwent ML. For the patients with either multiple lesions or a large lesion that required bracketing, multiple localization devices were placed in 31% of the WGL patients, 28% of the RSL patients, and 23% of the ML patients (p = 0.006). Negative margins were achieved in 91% of the WGL patients, 89% of the RSL patients, and 89% of the ML patients (p = 0.4). CONCLUSION: Localization of non-palpable breast lesions using Magseed is a safe and effective alternative to WGL and RSL that overcomes radiation safety limitations and increases radiology and surgery scheduling efficiency.

Impact of the early COVID-19 pandemic on Breast Surgical Oncology fellow education.

INTRODUCTION: The early COVID-19 pandemic rapidly transformed healthcare and medical education. We sought to evaluate the professional and personal impact of the pandemic on 2019-2020 Breast Surgical Oncology (BSO) fellows in Society of Surgical Oncology approved programs to capture the experience and direct future changes. METHODS: From July 15, 2020 to August 4, 2020 a survey was administered to the American Society of Breast Surgeons' fellow members. The survey assessed the impact of the pandemic on clinical experience, education/research opportunities, personal health/well-being, and future career. Responses were collected and aggregated to quantify the collective experience of respondents. RESULTS: Twenty-eight of fifty-seven (54%) eligible fellows responded. Twenty-one (75%) indicated the clinical experience changed. Twenty-seven (96%) reported less time spent caring for ambulatory breast patients and sixteen (57%) reported the same/more time spent in the operating room. Fourteen (50%) stated their future job was impacted and eight (29%) delayed general surgery board examinations. Stress was increased in 26 (93%). Personal health was unaffected in 20 (71%), and 3 (10%) quarantined for COVID-19 exposure/infection. CONCLUSION: The COVID-19 pandemic altered the clinical experience of BSO fellows; however, the operative experience was generally unaffected. The creation of frameworks and support mechanisms to mitigate potential challenges for fellows and fellowship programs in the ongoing pandemic and other times of national crisis should be considered.

Circulating Tumor Cells in Breast Cancer.

With active screening for early detection and advancements in treatment, there has been a significant decrease in mortality from breast cancer. However, a significant proportion of patients with non-metastatic breast cancer at time of diagnosis will relapse. Therefore, it is suggested that the dissemination of bloodstream tumor cells (circulating tumor cells, CTCs) undetectable by currently available diagnostic tools occurs during the early stages of breast cancer progression, and may be the potential source of micrometastases responsible for treatment failures. Here, we review the clinical significance of CTCs, as detected by the FDA-approved CellSearch® System, in both metastatic and non-metastatic breast cancer patients. Studies so far suggest that CTCs are prognostic of poorer outcomes in breast cancer patients; however, there is currently insufficient data to support use of CTC data to guide treatment. Therefore, there are ongoing studies to evaluate the utility of assessing CTC phenotypes to develop personalized breast cancer treatment, which will be reviewed in this chapter.

Break-induced replication promotes formation of lethal joint molecules dissolved by Srs2.

Break-induced replication (BIR) is a DNA double-strand break repair pathway that leads to genomic instabilities similar to those observed in cancer. BIR proceeds by a migrating bubble where asynchrony between leading and lagging strand synthesis leads to accumulation of long single-stranded DNA (ssDNA). It remains unknown how this ssDNA is prevented from unscheduled pairing with the template, which can lead to genomic instability. Here, we propose that uncontrolled Rad51 binding to this ssDNA promotes formation of toxic joint molecules that are counteracted by Srs2. First, Srs2 dislodges Rad51 from ssDNA preventing promiscuous strand invasions. Second, it dismantles toxic intermediates that have already formed. Rare survivors in the absence of Srs2 rely on structure-specific endonucleases, Mus81 and Yen1, that resolve toxic joint-molecules. Overall, we uncover a new feature of BIR and propose that tight control of ssDNA accumulated during this process is essential to prevent its channeling into toxic structures threatening cell viability.

Clinical outcomes following self-expanding metal stent placement for esophageal salvage.

OBJECTIVES: To assess the efficacy of self-expanding metal stents (SEMS) for esophageal salvage in patients who would otherwise require esophageal/conduit resection. METHODS: We performed a retrospective chart review of patients who had SEMS placed from January 2010 to December 2015. Patient demographics, esophageal stent characteristics, and outcomes were assessed in our patient cohort. RESULTS: Our study included a total of 83 patients. A total of 148 SEMS were placed, with 121 partially covered SEMS (pcSEMS) and 27 fully covered SEMS (cSEMS). A stent was placed more than once in 42.2% of the patients. Median duration of stent placement was 23 days. Indications for SEMS placement included esophageal leak after esophageal resection (45.8%), spontaneous esophageal perforation (22.9%), iatrogenic esophageal perforation (20.5%), and esophageal obstruction (9.6%). Complications from SEMS placement included 6 stent migrations and 1 esophageal perforation. Of the 6 stents that migrated, 2 were pcSEMS and 4 were cSEMS. In a patient who underwent stent placement for a stricture refractory to dilation, a perforation at the distal end was discovered 2 days after stent removal. The perforation healed after the second SEMS placement. Ultimately, 15 patients (18.1%) had to undergo a subsequent esophagectomy or takedown of their conduit with an overall 81.9% salvage of native esophagus or conduits. CONCLUSIONS: Our study demonstrates the successful use of SEMS in patients with anastomotic leaks, perforations, and recalcitrant strictures.

Management of gastric conduit dehiscence with self-expanding metal stents: a case report on salvaging the gastric conduit.

BACKGROUND: Three-hole minimally invasive esophagectomy (3HMIE) is one of the most radical procedures in gastrointestinal surgery. It involves thoracoscopic dissection of the esophagus followed by creation of a gastric conduit in the abdomen with anastomosis in the neck, and is associated with significant morbidity. Gastric conduit dehiscence is one of the most morbid complications following esophagectomy. Historically, the standard of care in this situation has been conduit diversion with delayed esophageal reconstruction. CASE PRESENTATION: Here, we report two patients with a timely diagnosis of gastric conduit dehiscence of staple line after 3HMIE who were salvaged successfully with endoscopic placement of self-expanding metal stents. CONCLUSION: Endoscopic stents may be used in selected cases of gastric conduit dehiscence after 3HMIE to salvage the conduit.

Cervical Esophago-Gastric Tubes for Patients with Malignant Ascites.

Patients with chronic small bowel obstruction and malignant ascites from diffuse peritoneal carcinomatosis have limited options for gastrointestinal decompression as part of end-of-life palliation. Insertion of a percutaneous gastrostomy tube is relatively contraindicated in patients with ascites. Alternatively, nasogastric tube placement often leads to significant discomfort to patients and necessitates hospitalization during their last days of life. Here, we demonstrate how placing a percutaneous cervical esophago-gastric tube can allow adequate gastrointestinal decompression for terminal patients with malignant small bowel obstruction. This palliative measure allows them to remain in the comfort of their own homes after the procedure.

Clinical outcomes of pancreaticoduodenectomy in octogenarians: a surgeon's experience from 2007 to 2015.

BACKGROUND: As the number of elderly people in our population increases, there will be a greater number of octogenarians who will need pancreaticoduodenectomy as the only curative option for periampullary malignancies. This study evaluated clinical outcomes of pancreaticoduodenectomy in octogenarians, in comparison to younger patients. METHODS: A retrospective review was conducted of 216 consecutive patients who underwent pancreaticoduodenectomy from January 2007 to April 2015. A two-sided Fisher's exact statistical analysis was used to compare pre-operative comorbidities, intra-operative factors, surgical pathology, and post-operative complication rates between non-octogenarians and octogenarians. RESULTS: One hundred and eighty three non-octogenarians and 33 octogenarians underwent pancreaticoduodenectomy. Of patients with periampullary adenocarcinoma, octogenarians were more likely to present with advanced disease state (P=0.01). The two cohorts had similar ASA scores (P=0.62); however, octogenarians were more likely to have coronary artery disease (P=0.03). The length of operation was shorter in octogenarians (P=0.002). Mortality rates (P=0.49) and overall postoperative complication rates (P=1.0) were similar in two cohorts; however octogenarians had a higher incidence of pulmonary embolism (P=0.02). CONCLUSIONS: Our data demonstrates that octogenarians can undergo pancreaticoduodenectomy with outcomes similar to those in younger patients. Thus, patients should not be denied a curative surgical option for periampullary malignancy based on advanced age alone.

The autophagy inhibitor chloroquine targets cancer stem cells in triple negative breast cancer by inducing mitochondrial damage and impairing DNA break repair.

Triple negative breast cancer (TNBC), characterized by an abundance of treatment-resistant breast cancer stem cells (CSCs), has a poorer prognosis than other types of breast cancers. Despite its aggressiveness, no effective targeted therapy exists for TNBC. Here, we demonstrate that CQ effectively targets CSCs via autophagy inhibition, mitochondrial structural damage, and impairment of double-stranded DNA break repair. Electron microscopy demonstrates CQ-induced mitochondrial cristae damage, which leads to mitochondrial membrane depolarization with a significant reduction in the activity of cytochrome c oxidase and accumulation of superoxide and double-stranded DNA breaks. CQ effectively diminishes the TNBC cells' ability to metastasize in vitro and in a TNBC xenograft model. When administered in combination with carboplatin, CQ effectively inhibits carboplatin-induced autophagy. This combination treatment significantly diminishes the expression of DNA repair proteins in CSC subpopulations, resulting in tumor growth reduction in carboplatin-resistant BRCA1 wild-type TNBC orthotopic xenografts. As TNBC's high treatment failure rate has been attributed to enrichment of CSCs, CQ, an autophagy inhibitor with anti-CSC effects, may be an effective adjunct to current TNBC chemotherapy regimens with carboplatin.

Cell-free DNA as a molecular tool for monitoring disease progression and response to therapy in breast cancer patients.

Due to the spatial and temporal genomic heterogeneity of breast cancer, genomic sequencing obtained from a single biopsy may not capture the complete genomic profile of tumors. Thus, we propose that cell-free DNA (cfDNA) in plasma may be an alternate source of genomic information to provide comprehensive data throughout a patient's clinical course. We performed a retrospective chart review of 100 patients with stage 4 or high-risk stage 3 breast cancer. The degree of agreement between genomic alterations found in tumor DNA (tDNA) and cfDNA was determined by Cohen's Kappa. Clinical disease progression was compared to mutant allele frequency using a two-sided Fisher's exact test. The presence of mutations and mutant allele frequency was correlated with progression-free survival (PFS) using a Cox proportional hazards model and a log-rank test. The most commonly found genomic alterations were mutations in TP53 and PIK3CA, and amplification of EGFR and ERBB2. PIK3CA mutation and ERBB2 amplification demonstrated robust agreement between tDNA and cfDNA (Cohen's kappa = 0.64 and 0.77, respectively). TP53 mutation and EGFR amplification demonstrated poor agreement between tDNA and cfDNA (Cohen's kappa = 0.18 and 0.33, respectively). The directional changes of TP53 and PIK3CA mutant allele frequency were closely associated with response to therapy (p = 0.002). The presence of TP53 mutation (p = 0.0004) and PIK3CA mutant allele frequency [p = 0.01, HR 1.074 (95 % CI 1.018-1.134)] was excellent predictors of PFS. Identification of selected cancer-specific genomic alterations from cfDNA may be a noninvasive way to monitor disease progression, predict PFS, and offer targeted therapy.

Bypass grafting between the supraceliac aorta and the common hepatic artery during pancreaticoduodenectomy.

Patients with celiac artery stenosis often remain asymptomatic due to formation of extensive collateral pathways. Hepatic or anastomotic ischemia may occur when the gastroduodenal artery and these collaterals are ligated during pancreaticoduodenectomy. Here, we present a patient with severe atherosclerotic disease of the celiac axis who successfully underwent pancreaticoduodenectomy with aorto-hepatic bypass.