Axillary lymph node recurrence following wire-directed sentinel lymph node dissection for breast cancer patients with biopsy-proven axillary metastases prior to neoadjuvant chemotherapy at a safety net medical center.

BACKGROUND: Although sentinel lymph node dissection (SLND) after neoadjuvant chemotherapy (NAC) is feasible, axillary management for patients with pretreatment biopsy-proven axillary metastases and who are clinically node-negative after NAC (ycN0) remains unclear. This retrospective study was performed to determine the rate of axillary lymph node recurrence for such patients who had wire-directed (WD) SLND. METHODS: Patients treated with NAC from 2015 to 2020 had axillary nodes evaluated by pretreatment ultrasound. Core biopsies were done on abnormal nodes, and microclips were placed in nodes during biopsy. For patients with biopsy-proven node metastases who received NAC and were ycN0 by clinical exam, WD SLND was done. Patients with negative nodes on frozen section had WD SLND alone; those with positive nodes had WD SLND plus axillary lymph node dissection (ALND). RESULTS: Of 179 patients receiving NAC, 62 were biopsy-proven node-positive pre-NAC and ycN0 post-NAC. Thirty-five (56%) patients were node-negative on frozen section and had WD SLND alone. Twenty-seven (43%) patients had WD SLND + ALND. Forty-seven patients had postoperative regional node irradiation. With median follow-up of 40 months, there were recurrences in 4 (11%) of 35 patients having WD SLND and 5 (19%) of 27 having WD SLND + ALND, but there was only one axillary lymph node recurrence, identified by CT scan. CONCLUSIONS: Axillary node recurrence was very uncommon after WD SLND for patients who had pretreatment biopsy-proven node metastases and were ypN0 after NAC. These patients would be unlikely to derive clinical benefit from the addition of completion ALND to SLND.

The prognostic value of early measures of the ventilatory ratio in the ARDS ROSE trial.

BACKGROUND: The ventilatory ratio (VR, [minute ventilation × PaCO2]/[predicted body weight × 100 × 37.5]) is associated with mortality in ARDS. The aims of this study were to test whether baseline disease severity or neuromuscular blockade (NMB) modified the relationship between VR and mortality. METHODS: This was a post hoc analysis of the PETAL-ROSE trial, which randomized moderate-to-severe ARDS patients to NMB or control. Survival among patients with different VR trajectories or VR cutoff above and below the median was assessed by Kaplan-Meier analysis. The relationships between single-day or 48-h VR trajectories with 28- or 90-day mortality were tested by logistic regression. Randomization allocation to NMB and markers of disease severity were tested as confounders by multivariable regression and interaction term analyses. RESULTS: Patients with worsening VR trajectories had significantly lower survival compared to those with improving VR (n = 602, p < 0.05). Patients with VR > 2 (median) at day 1 had a significantly lower 90-day survival compared to patients with VR ≤ 2 (HR 1.36, 95% CI 1.10-1.69). VR at day 1 was significantly associated with 28-day mortality (OR = 1.40, 95% CI 1.15-1.72). There was no interaction between NMB and VR for 28-day mortality. APACHE-III had a significant interaction with VR at baseline for the outcome of 28-day mortality, such that the relationship between VR and mortality was stronger among patients with lower APACHE-III. There was a significant association between rising VR trajectory and mortality that was independent of NMB, baseline PaO2/FiO2 ratio and generalized markers of disease severity (Adjusted OR 1.81, 95% CI 1.28-2.84 for 28-day and OR 2.07 95% CI 1.41-3.10 for 90-day mortality). APACHE-III and NMB were not effect modifiers in the relationship between VR trajectory and mortality. CONCLUSIONS: Elevated baseline and day 1 VR were associated with higher 28-day mortality. The relationship between baseline VR and mortality was stronger among patients with lower APACHE-III. APACHE-III was not an effect modifier for the relationship between VR trajectory and mortality, so that the VR trajectory may be optimally suited for prognostication and predictive enrichment. VR was not different between patients randomized to NMB or control, indicating that VR can be utilized without correcting for NMB.

Effects of paravertebral blocks versus liposomal bupivacaine on hospital utilization after mastectomy with reconstruction.

INTRODUCTION: Inadequate pain control frequently extends length of stay (LOS) and costs for patients undergoing mastectomy with implant-based reconstruction (IBR). We sought to examine the effects of Paravertebral blocks (PVB) and liposomal bupivacaine (LB) and compare LOS, pain scores and costs of hospitalization. METHODS: Prospective database review of patients undergoing mastectomy with IBR was performed. RESULTS: 541 patients were identified. 51/491 (9.4%) received PVB and 50 (9.2%) received LB. LOS in the PVB group was significantly less than that of the no block (NB) group (1 [1-2] days PVB vs 3 [2-4] days NB (p < 0.0001), but was not different from the LB group (1 [1-2] days LB, p = 0.23). PVB patients had lower PACU pain scores compared to NB patients (3.2 ± 2.9 PVB vs 5.7 ± 2.6 NB, p < 0.0001), but similar PACU pain scores to LB patients (4.1 ± 2.3). Patients who received PVB had higher total costs compared to NB patients ($27148±$7053 PVB vs $23113 ± 6860 NB, p = 0.003) but similar to LB patients ($26183 ± $3761). CONCLUSION: PVB and LB are associated with shorter LOS and lower pain scores compared to NB.

Ventilatory Ratio Is a Valuable Prognostic Indicator in an Observational Cohort of Patients With ARDS.

BACKGROUND: How indices specific to respiratory compromise contribute to prognostication in patients with ARDS is not well characterized in general clinical populations. The primary objective of this study was to identify variables specific to respiratory failure that might add prognostic value to indicators of systemic illness severity in an observational cohort of subjects with ARDS. METHODS: Fifty subjects with ARDS were enrolled in a single-center, prospective, observational cohort. We tested the contribution of respiratory variables (oxygenation index, ventilatory ratio [VR], and the radiographic assessment of lung edema score) to logistic regression models of 28-d mortality adjusted for indicators of systemic illness severity (the Acute Physiology and Chronic Health Evaluation [APACHE] III score or severity of shock as measured by the number of vasopressors required at baseline) using likelihood ratio testing. We also compared a model utilizing APACHE III with one including baseline number of vasopressors by comparing the area under the receiver operating curve (AUROC). RESULTS: VR significantly improved model performance by likelihood ratio testing when added to APACHE III (P = .036) or the number of vasopressors at baseline (P = .01). Number of vasopressors required at baseline had similar prognostic discrimination to the APACHE III. A model including the number of vasopressors and VR (AUROC 0.77 [95% CI 0.64-0.90]) was comparable to a model including APACHE III and VR (AUROC 0.81 [95% CI 0.68-0.93]; P for comparison = .58.). CONCLUSIONS: In this observational cohort of subjects with ARDS, the VR significantly improved discrimination for mortality when combined with indicators of severe systemic illness. The number of vasopressors required at baseline and APACHE III had similar discrimination for mortality when combined with VR. VR is easily obtained at the bedside and offers promise for clinical prognostication.

Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS.

The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a "cytokine storm," we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.

Effect of surgical complications on outcomes in breast cancer patients treated with mastectomy and immediate reconstruction.

BACKGROUND: Operative complications affect recurrence in non-breast malignancies. Rising rates of mastectomy with immediate reconstruction and their increased post-operative complications fuel concerns for poorer outcome in breast cancer (BC). We sought to determine the effect of complications on recurrence in BC patients. METHODS: A single-institution retrospective review was conducted of incident BC treated with mastectomy and immediate reconstruction. Overall survival and recurrence were compared between patients with complications to those without. RESULTS: Of 201 patients (350 mastectomies, 86 nipple-sparing), 62 (30.8%) had a surgical complication. Patients with complications were older, but groups were similar for type of reconstruction, tobacco use, hormone receptor status, HER2, lymphovascular invasion, and pathologic stage (all p > 0.05). Twenty-two complications (10.9%) were infection, 5 (2.5%) dehiscence, 14 flap necrosis (7%), 21 hematomas (10.4%), and 8 nipple necroses (9%). Recurrence occurred in 18 (8.9%) patients: 4 local, 2 regional, and 12 distant. After 8.9 years of median follow-up, patients with complications trended towards higher recurrence (hazard ratio (HR) 2.23, log-rank p = 0.08, Cox regression p = 0.05), particularly with nipple necrosis (HR 3.28, log-rank p = 0.09, regression p = 0.06). Patients with other complications had similar recurrence-free survival to those without (all p > 0.05). Higher stage (HR 13.66, log-rank p = 0.03) and adjuvant radiation (HR 2.78, log-rank p = 0.04) cases were more likely to recur. Patients with complications had similar overall survival to those without (log-rank p > 0.05). CONCLUSION: BC patients with surgical complications do not have lower overall survival. This finding may be due to the improved prognosis compared to non-breast malignancies.

Inhibition of the lipoxin A4 and resolvin D1 receptor impairs host response to acute lung injury caused by pneumococcal pneumonia in mice.

Resolution of the acute respiratory distress syndrome (ARDS) from pneumonia requires repair of the injured lung endothelium and alveolar epithelium, removal of neutrophils from the distal airspaces of the lung, and clearance of the pathogen. Previous studies have demonstrated the importance of specialized proresolving mediators (SPMs) in the regulation of host responses during inflammation. Although ARDS is commonly caused by Streptococcus pneumoniae, the role of lipoxin A4 (LXA4) and resolvin D1 (RvD1) in pneumococcal pneumonia is not well understood. In the present experimental study, we tested the hypothesis that endogenous SPMs play a role in the resolution of lung injury in a clinically relevant model of bacterial pneumonia. Blockade of formyl peptide receptor 2 (ALX/FPR2), the receptor for LXA4 and RvD1, with the peptide WRW4 resulted in more pulmonary edema, greater protein accumulation in the air spaces, and increased bacteria accumulation in the air spaces and the blood. Inhibition of this receptor was also associated with decreased levels of proinflammatory cytokines. Even in the presence of antibiotic treatment, WRW4 inhibited the resolution of lung injury. In summary, these experiments demonstrated two novel findings: LXA4 and RvD1 contribute to the resolution of lung injury due to pneumococcal pneumonia, and the mechanism of their benefit likely includes augmenting bacterial clearance and reducing pulmonary edema via the restoration of lung alveolar-capillary barrier permeability.

Changes in utilization of axillary dissection in women with invasive breast cancer and sentinel node metastasis after the ACOSOG Z0011 trial.

The American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial demonstrated no survival advantage for women with clinical T1-T2 invasive breast cancer with 1-2 positive sentinel lymph nodes (SLN) who received whole-breast radiation, and no further axillary surgery when compared to women who did undergo axillary lymph node dissection (ALND). We used the National Cancer Database (NCDB) to study changes in utilization of ALND after the publication of this trial. NCDB was queried for female patients from 2012 to 2015 who met Z0011 criteria. Patients were divided into four groups based on Commission on Cancer facility accreditation. Outcome measures include the rate of ALND (nonadherence to Z0011) and the average number of nodes retrieved with ALND. 27,635 patients were identified, with no significant differences in T stage and receptor profiles between groups. Overall rate of ALND decreased from 34.0% in 2012 to 22.7% in 2015. Nonadherence was lowest in Academic Programs (decreasing from 30.1% in 2012 to 20.5% in 2015) and was highest in Community Cancer Programs (41.2% in 2012 to 29.1% in 2015). Median number of positive SLN did not differ between groups (p = .563). Median number of nodes retrieved on ALND decreased from 9 (IQR 5-14) in 2012 to 7 (IQR 4-12) in 2015 (p < .001). In patients who met the ACOSOG Z11 trial guidelines, rates of ALND have decreased over time. However, rates of nonadherence to Z0011 are significantly higher in Community Cancer Programs compared to Academic Programs.

Erroneous diagnosis of primary fibrosarcoma of the breast: The value of the multidisciplinary breast team approach.

Diagnostic errors occur in the preanalytic, analytic, and postanalytic phases of specimen processing. Correlating clinical and imaging information with gross and microscopic findings is crucial to limit errors and unnecessary treatment. Herein, we report the case of a 54-year-old woman who presented with left breast bloody nipple discharge and subsequently underwent central duct excision. Pathology revealed a high-grade sarcoma. The patient presented to our institution for further management. Upon secondary pathology review and DNA fingerprinting analysis, the correct interpretation was rendered. Our case demonstrates the importance of clinical correlation and review of pathology slides prior to definitive therapy.

COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and is modified by dexamethasone.

We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with the acute respiratory distress syndrome (ARDS) from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a cytokine storm, we observed reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS was characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 was characterized by impaired interferon-stimulated gene expression (ISG). We found that the relationship between SARS-CoV-2 viral load and expression of ISGs was decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients with COVID-19 ARDS did not demonstrate cytokine storm but instead revealed a unique and dysregulated host response predicted to be modified by dexamethasone.

Phenotypes and personalized medicine in the acute respiratory distress syndrome.

Although the acute respiratory distress syndrome (ARDS) is well defined by the development of acute hypoxemia, bilateral infiltrates and non-cardiogenic pulmonary edema, ARDS is heterogeneous in terms of clinical risk factors, physiology of lung injury, microbiology, and biology, potentially explaining why pharmacologic therapies have been mostly unsuccessful in treating ARDS. Identifying phenotypes of ARDS and integrating this information into patient selection for clinical trials may increase the chance for efficacy with new treatments. In this review, we focus on classifying ARDS by the associated clinical disorders, physiological data, and radiographic imaging. We consider biologic phenotypes, including plasma protein biomarkers, gene expression, and common causative microbiologic pathogens. We will also discuss the issue of focusing clinical trials on the patient's phase of lung injury, including prevention, administration of therapy during early acute lung injury, and treatment of established ARDS. A more in depth understanding of the interplay of these variables in ARDS should provide more success in designing and conducting clinical trials and achieving the goal of personalized medicine.

Treatment at Academic Centers Increases Likelihood of Reconstruction After Mastectomy for Breast Cancer Patients.

BACKGROUND: Mastectomy rates continue to increase in women diagnosed with breast cancer (BC). There are limited data regarding reconstruction rates at academic centers (AC) versus community hospitals (CH). We aim to determine the effect of facility type on reconstruction rates. MATERIALS AND METHODS: The National Cancer Database was queried for BC patients treated with mastectomy from 2004 to 2014. Clinical characteristics and type of reconstruction were compared between treatment at AC or CH. RESULTS: A total of 860,509 patients were included. Patients treated at AC were younger (58.7 ± 12 y AC versus 61.6 ± 13 y CH; P < 0.001) and traveled farther to their treatment center (33.1 ± 122.8 miles AC versus 20 ± 75.3 miles CH; P < 0.001). Patients undergoing surgery at AC were more likely to have reconstruction than those at CH (43.7% AC versus 32.5% CH; P < 0.001). This trend remained across all reconstruction types including expander/implant-based reconstruction (immediate breast reconstruction) (14.4% AC versus 9.9% CH), autologous reconstruction (14.9% AC versus 11.7% CH), mixed reconstruction (5.2% AC versus 3.6% CH), and other reconstructions (9.2% AC versus 7.3% CH) (all P < 0.001). Patients in all age categories, across insurance statuses, and with comorbidities were more likely to receive reconstruction if treated at AC compared with CH. In multivariate analysis, having a mastectomy at AC was an independent predictor of reconstruction (adjusted odds ratio, 1.51; 95% confidence interval, 1.49-1.51; P < 0.001). CONCLUSIONS: Undergoing mastectomy at AC results in higher rate of reconstruction compared with CH.

Breast cancer lung metastasis: Molecular biology and therapeutic implications.

Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

Multifocality in Small Bowel Neuroendocrine Tumors.

BACKGROUND: Neuroendocrine tumors (NETs) account for 30% of small bowel (SB) neoplasms. The objectives of this study were to evaluate the incidence of multifocality in primary small bowel neuroendocrine tumors (SBNETs) and to examine the associated outcomes. METHODS: Patients with multifocal SBNET were compared to those with a solitary lesion. Only patients who underwent diagnostic workup and surgical intervention at our institution were included in this study. The primary aim of our study was surgical outcomes and mortality and recurrence. The second aim of our study was to evaluate the utility of double-balloon enteroscopy (DBE) and capsule endoscopy. RESULTS: Of 178 patients with SBNETs during the study period, 85 met inclusion criteria. The mean age was 61.0 ± 12.6 years and 44.7% were male. The ileum was the primary tumor site for 66 patients (77.7%). Of DBE patients, 28 (62.2%) had additional lesions identified, of which 23 (82.1%) had NET confirmed on pathology. Average tumor size was 1.8 cm and most were well differentiated (89.9%), with Ki-67 of ≥ 2% (65.8%); 74.4% had nodal metastases and 51% of patients had stage IV disease. Forty-six patients (54.1%) had multifocal disease, of whom 37 (80.5%) had an ileal primary. No differences in survival or recurrence were seen for multifocal versus solitary disease. CONCLUSIONS: SBNETs have a high incidence of multifocality. DBE can be used in the preoperative assessment to detect multifocal NET. Multifocality has no impact on survival or recurrence outcomes.

Long-Term Outcomes after Elective versus Emergency Surgery for Small Bowel Neuroendocrine Tumors.

Small bowel neuroendocrine tumors (SBNETs) are often indolent, but occasionally, patients present with acute symptoms requiring emergent operative intervention. Our aim was to determine whether emergency surgery for SBNETs affects long-term outcomes. An institutional database was reviewed to identify patients with SBNET diagnosed between 1990 and 2015. Need for emergency resection (ER) was compared with elective resection (ELR). One hundred and thirty-four patients met inclusion criteria. Median age was 59 years (range, 21-91), and median tumor size was 1.5 cm (range, 0.1-5). Median follow-up time was 5.5 years. One hundred (74.6%) patients had ELR, whereas 34 (25.4%) required ER. ELR had a higher number of lymph nodes resected (median 12.5 vs 8 ER, P = 0.04); however, there was no difference in the number of positive nodes (median 3 vs 2, P = 0.85). There were 45 (33.6%) recurrences (31 [31.0%] ELR vs 14 [41.7%] ER, P = 0.29) and 13 (9.7%) deaths (7 [7.0%] ELR; 6 [17.6%] ER). There was no significant difference in 5-year disease-free survival (ELR 72.6% vs ER 77.9%, P = 0.71) or overall survival (ELR 97.2% vs ER 96.6%, P = 0.81). Although patients undergoing ER have significantly fewer lymph nodes resected, they have comparable recurrence rates and long-term outcomes with those patients undergoing ER.

Menopausal Status and Outcomes of BRCA Mutation Carriers with Breast Cancer.

Outcomes based on menopausal status of breast cancer (BC) patients who are BRCA mutations carriers (BRCAm) are not well known. A prospective database identified 88 BRCAm with BC from 2005 to 2015. Of the 88 patients, 68 (77.3%) women were premenopausal (Pre-M) and 20 (22.7%) were postmenopausal (Post-M). In the Pre-M group, 52.9 per cent of patients had triple-negative (TN) BC, whereas in the Post-M group, there were more estrogen receptor +(65%; P = 0.129) and less TN (25%; P = 0.041) tumors. Median tumor size was significantly larger in the Pre-M group compared with the Post-M group (P <0.001). Pre-M women were more likely to present with stage III cancers (14.7% vs 0%, respectively, P = 0.082). Ten-year overall survival was 87.9 per cent in the Pre-M group and 93.8 per cent in the Post-M group (P = 0.44), and 25.3 per cent of Pre-M women had recurrences compared with 11.5 per cent of Post-M women (P = 0.24). Premenopausal BRCAm with BC are more likely to have TN, higher stage disease, and twice the number of recurrences at 10 years than Post-M BRCAm. Our study is the first to show worse BC outcomes for Pre-M BRCAm compared with Post-M BRCAm women.