Extremely Low Incidence of Local-Regional Recurrences Observed Among T1-2 N1 (1 or 2 Positive SLNs) Breast Cancer Patients Receiving Upfront Mastectomy Without Completion Axillary Node Dissection.

BACKGROUND: Completion axillary node dissection (CLND) is routinely omitted in cT1-2 N0 breast cancer treated with upfront, breast-conserving therapy and sentinel node biopsy (SLNB) showing one to two positive sentinel nodes (SLNs). The purpose of this study was to determine the incidence and impact of axillary treatment among patients treated with mastectomy in a contemporary cohort. METHODS: A prospective, institutional database was reviewed from 2006 to 2015 to identify patients with T1-2 breast cancer treated with upfront mastectomy and SLNB found to have one to two positive SLNs. Patients were stratified by axillary therapy [including CLND and/or post-mastectomy radiation therapy (PMRT)], and clinicopathologic factors and incidence rates of local-regional and distant recurrence were analyzed. RESULTS: A total of 548 patients were identified, including 126 (23%) without CLND. Rates of PMRT were similar between those with and without CLND (35.3% vs. 28.6%, p = 0.16). On multivariate analysis, two rather than one positive SLN, larger SLN metastasis size, frozen-section analysis of the SLNB, and adjuvant chemotherapy were significantly associated with receipt of CLND. At a median follow-up of 7 years, there were only two local-regional recurrences in the no-CLND group, of which only one was an axillary recurrence. The 5-years incidence rate of LRR was not significantly different for those with and without CLND (1.3% vs. 1.8%, p = 0.93). CONCLUSIONS: We found extremely low rates of local-regional recurrence among those with T1-2 breast cancer undergoing upfront mastectomy with 1-2 positive SLNs. Further axillary surgery may not be indicated in selected patients treated with a multidisciplinary approach, including adjuvant therapies.

Outcomes of Sentinel Lymph Node-Positive Breast Cancer Patients Treated with Mastectomy Without Axillary Therapy.

PURPOSE: Early-stage breast cancer patients with minimal axillary disease identified by sentinel lymph node dissection (SLND) have low regional recurrence rates when treated with breast-conserving surgery and radiation therapy (XRT) and many avoid a completion axillary lymph node dissection (CLND). As the incidence of total mastectomy (TM) has increased, it has become important to characterize which TM patients with a positive SLN may not benefit from further axillary treatment. METHODS: An institutional database was utilized to identify patients treated with a TM for invasive breast cancer and who had a positive SLN from 1994 to 2010. Clinicopathologic factors were analyzed. Regional recurrence rate, recurrence-free survival (RFS), and overall survival (OS) were determined. RESULTS: A total of 525 patients with invasive breast cancer and a positive SLN were treated with TM, including 58 patients who did not have CLND or XRT and 12 patients who did not have CLND but did receive XRT. Median follow-up was 66 months. The incidence of regional recurrence was not significantly different for patients who received no further axillary treatment compared to those who underwent CLND without XRT or those treated with XRT without CLND (10 years rate: 3.8 vs. 1.6 and 0 % respectively). RFS and OS were not significantly different among patients who received no further axillary treatment compared to those who underwent CLND, XRT, or both. CONCLUSIONS: In select patients with early-stage breast cancer treated with mastectomy with a positive SLN, CLND may be avoided without adversely affecting recurrence or survival.

Incidence and consequence of close margins in patients with ductal carcinoma-in situ treated with mastectomy: is further therapy warranted?

BACKGROUND: The impact of close margins in patients with ductal carcinoma-in situ (DCIS) treated with mastectomy is unclear; however, this finding may lead to a recommendation for postmastectomy radiotherapy (PMRT). We sought to determine the incidence and consequences of close margins in patients with DCIS treated with mastectomy. METHODS: The records of 810 patients with DCIS treated with mastectomy from 1996 through 2009 were reviewed. Clinical and pathologic factors were analyzed with respect to final margin status. Median follow-up was 6.3 years. RESULTS: Overall, 94 patients (11.7 %) had close margins (positive, n = 5; negative but ≤1 mm, n = 54; 1.1-2.9 mm, n = 35). Independent risk factors for close margins included multicentricity, pathologic lesion size ≥1.5 cm, and necrosis, but not age, use of skin-sparing mastectomy, or immediate reconstruction (p > 0.05). Seven patients received PMRT, and none had a locoregional recurrence (LRR). Among the remaining 803 patients, the 10-year LRR rate was 1 % (5.0 % for margins ≤1 mm, 3.6 % for margins 1.1-2.9 mm, and 0.7 % for margins ≥3 mm [p < 0.001]). The 10-year rate of contralateral breast cancer was 6.4 %. On multivariate analysis, close margins was the only independent predictor of LRR (p = 0.005). CONCLUSIONS: Close margins occur in a minority of patients undergoing mastectomy for DCIS and is the only independent risk factor for LRR. As the LRR rate in patients with close margins is low and less than the rate of contralateral breast cancer, PMRT is not warranted except for patients with multiple close/positive margins that cannot be surgically excised.

Discordance between lactate and base deficit in the surgical intensive care unit: which one do you trust?

PURPOSE: Both lactate and base deficit (BD) are used as predictors of injury severity and mortality. We examined the significance of these measures when used in combination, and particularly when they provide conflicting data. METHODS: We reviewed all intensive care unit patients with simultaneously obtained lactate and BD measurements. The ability to predict mortality and hospital stay was compared alone, in combination, and when there was disagreement between the measures. Receiver operating characteristic curves were generated to compare predictive abilities. RESULTS: There were 1,298 patients with 12,197 sets of paired laboratory data; 1,026 trauma patients and 272 surgical patients. Lactic acidosis was present in 41% and a significant BD level (> 2) was found in 52%. Nonsurvivors had higher admission lactate (6.2 vs. 3.3) and base deficit (6.1 vs. 3.2) levels than survivors (both P < .01), with a modest correlation (r = .52) between the measures. The admission lactate and BD levels had similar predictive ability for mortality, with areas under the receiver operating characteristic curve of .7 and .66, respectively (both P < .01). However, the predictive ability of the BD level decreased significantly during the intensive care unit stay (area, .5) compared with lactate level (area, .68). Lactate and BD levels disagreed in 44% of all laboratory sets. In patients with a normal lactate level (< 2.2), the BD level had no predictive ability for mortality (area, .48; P = .26). However, in patients with a normal BD level (< 2.0), the lactate level retained its predictive ability for mortality (area, .67; P < .01). Lengths of stay were longer among patients with an increased lactate level, even when the BD level was normal. There was no improvement in predictive ability using a combination of the 2 measures. CONCLUSIONS: Both lactate and BD levels may be used to identify lactic acidosis and predict mortality at admission. Increased lactate levels predict mortality and a prolonged course regardless of the associated BD level, whereas an increased BD level has no predictive value if the lactate level is normal.

Use of serum bicarbonate measurement in place of arterial base deficit in the surgical intensive care unit.

HYPOTHESIS: Serum bicarbonate (HCO(3)) measurement may accurately and reliably be substituted for the arterial base deficit (BD) assay in the surgical intensive care unit (ICU). DESIGN: Retrospective criterion standard analysis. SETTING: Surgical ICU in a tertiary care facility. PATIENTS: Consecutive sample of non-trauma-related surgical ICU admissions from January 1996 to January 2004 with simultaneously obtained serum HCO(3) and arterial BD levels. MAIN OUTCOME MEASURES: Correlation between HCO(3) and BD at admission and during the ICU stay; predictive value of serum HCO(3) for significant metabolic acidosis and ICU mortality. RESULTS: The study included 2291 patients with 26 063 sets of paired laboratory data. The mean +/- SD age was 52 +/- 16 years and mean ICU stay was 5.8 +/- 9.8 days. There were 174 ICU deaths (8%). Serum HCO(3) levels showed significant correlation with arterial BD levels both at admission (r = 0.85, R(2) = 0.72, P<.001) and throughout the ICU stay (r = 0.88, R(2) = 0.77, P<.001). Serum HCO(3) reliably predicted the presence of significant metabolic acidosis (BD > 5) with an area under the receiver operating characteristic curve (AUC) of 0.93 at admission and 0.95 overall (both P<.001), outperforming pH (AUC, 0.80), anion gap (AUC, 0.70), and lactate (AUC, 0.70). The admission serum HCO(3) level predicted ICU mortality as accurately as the admission arterial BD (AUCs of 0.68 and 0.70, respectively) and more accurately than either admission pH or anion gap. CONCLUSIONS: Serum HCO(3) provides equivalent information to the arterial BD and may be used as an alternative predictive marker or guide to resuscitation. Low HCO(3) levels should prompt immediate metabolic acidosis evaluation and management.

Serum bicarbonate may replace the arterial base deficit in the trauma intensive care unit.

OBJECTIVE: Arterial base deficit (BD) is a commonly used marker of injury severity and endpoint of resuscitation but requires an arterial puncture and blood gas analysis. Serum bicarbonate (HCO3) is routinely obtained as part of the chemistry panel on most admissions. We hypothesized that serum HCO3 strongly correlates with arterial BD and provides equivalent predictive information. METHODS: All trauma ICU admissions from 1996 to 2004 with simultaneously obtained serum chemistry panels and arterial blood gases were identified. Correlation between BD and HCO3 was analyzed by using linear regression, and predictive abilities for acidoses and mortality were compared using the area under the respective receiver operating characteristic curve (AUC). Separate analyses were done for the entire dataset and the subset of ICU admission laboratory values. RESULTS: We identified 3,102 patients with 50,311 matched pairs of laboratory data. Serum HCO3 showed a significant linear correlation with BD for all laboratory sets (r = 0.85, P < .01) and admission laboratory values only (r = 0.80, P < .01). Serum HCO3 reliably predicted the presence of significant metabolic acidoses (BD >5), with an AUC of 0.96 (P < .01), which clearly outperformed pH (AUC = 0.83), anion gap (AUC = 0.7), and lactate (AUC = 0.73). The mean admission BD among survivors was 2.5 versus 5.2 for nonsurvivors (P < .01), and the mean HCO3 was 17.7 versus 19.8 (P < .01). The admission HCO3 identified nonsurvivors as accurately as BD (AUCs of 0.66 and 0.68) and more accurately than either pH (AUC = 0.53) or anion gap (AUC = 0.6). CONCLUSION: Serum HCO3 measurement shows a strong linear correlation and similar predictive ability compared with the arterial BD. Serum HCO3 may be safely and accurately substituted for arterial BD measurement in critically injured patients.

Reduction in airway complications after lung transplantation with novel anastomotic technique.

BACKGROUND: Bronchial anastomotic complications develop in 31% of lung transplant recipients, leading to additional operative procedures and increased morbidity. Advances in surgical technique have thus far resulted in only modestly improved outcomes. We hypothesized that creating the bronchial anastomosis at the secondary carina using a combination of running and figure-of-eight sutures would minimize donor bronchial ischemia and airway complications. METHODS: This retrospective review of a single surgeon's operative experience from 2000 to 2007 compares a new bronchial anastomotic technique with the conventional technique. The primary outcome was the occurrence of bronchial anastomotic complications requiring invasive intervention. The secondary outcome was distal airway complications. Patients were monitored for 1 year after transplant. Recipient and donor demographic data as well as relevant variables from their preoperative, perioperative, and postoperative courses were collected for analysis. These data were compared using t tests for normally distributed continuous variables, Mann-Whitney tests for nonnormally distributed continuous variables, and χ2 tests or Fisher exact test for categoric variables. Logistic regression was used to control for covariates while comparing the primary outcome between the new and conventional bronchial anastomotic techniques. RESULTS: The analysis included 230 patients, representing 407 anastomoses. The occurrence of anastomotic complications requiring intervention and distal airway complications decreased from 18.1% to 2.3% of anastomoses and 12.2% to 4.4% of patients, respectively. After controlling for available risk factors, the new technique significantly reduced both anastomotic (p<0.001) and distal (p=0.03) airway complications. CONCLUSIONS: This new anastomotic technique dramatically reduces anastomotic and distal airway complications after lung transplantation.

Synergistic protection in lung ischemia-reperfusion injury with calcineurin and thrombin inhibition.

BACKGROUND: Ischemia-reperfusion injury impairs lung transplant outcomes. The transcription factors, activator protein-1, and nuclear factor kappa B, are activated early in reperfusion and drive the development of injury. Thrombin inhibition with hirudin, and calcineurin inhibition with tacrolimus have independently been shown to ameliorate lung ischemia-reperfusion injury by reducing activator protein-1 and nuclear factor kappa B activation, respectively. However, high doses were required to achieve protection using individual agents, raising concerns about potential toxicities. We sought to determine if low-dose combination therapy reduced injury through synergistic inhibition of pretranscriptional signaling events. METHODS: Rats were pretreated with either intravenous hirudin or tacrolimus at low doses or high doses, or both at low doses, prior to undergoing left lung ischemia and reperfusion. Lungs were assessed for markers of lung injury, including bronchoalveolar lavage cytokine-chemokine content and transcription factor transactivation of activator protein-1 and nuclear factor kappa B. RESULTS: High-dose monotherapy with hirudin or tacrolimus reduced lung injury and transactivation of activator protein-1 and nuclear factor kappa B activation, respectively, whereas low-dose monotherapy with either agent did not alter transcription factor activation or lung injury compared with positive controls. Low-dose combination therapy was more protective than high-dose monotherapy with either drug, and correlated with a reduction in activation of both transcription factors and their associated cytokines. CONCLUSIONS: The significant decrease in lung injury severity and transcription factor activation with combined pathway inhibition suggests pretranscriptional signaling redundancy between the calcineurin and thrombin dependent pathways in lung reperfusion injury.

Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion injury.

BACKGROUND: The availability of suitable lung donors has remained a significant barrier to lung transplantation. The clinical relevance of an isolated positive Gram stain in potential donor lungs, which occurs in >80%, is unclear. Low doses of lipopolysaccharide (LPS) have been protective in several models of ischemia-reperfusion injury through a pre-conditioning response. We sought to demonstrate that low-dose LPS is protective against subsequent lung ischemia-reperfusion injury. METHODS: Pathogen-free Long-Evans rats were pre-treated with vehicle or LPS 24 hours before 90 minutes of ischemia and up to 4 hours of reperfusion. Lungs were assessed for vascular permeability, myeloperoxidase content, bronchoalveolar lavage inflammatory cell and cytokine/chemokine content, as well as nuclear translocation of nuclear factor kappaB (NFkappaB) and activator protein-1 (AP-1), and interleukin-1 receptor-associated kinase-1 (IRAK-1) and stress-activated protein kinase (SAPK) activation. RESULTS: Compared with positive controls, LPS pre-treatment resulted in reductions in vascular permeability (70%, p < 0.001), myeloperoxidase content (93%, p < 0.001), bronchoalveolar lavage inflammatory cells (91%, p < 0.001), and inflammatory cytokine/chemokine content (cytokine-induced neutrophil chemoattractant, 99%, p = 0.003; interleukin-1beta, 72%, p < 0.0001; tumor necrosis factor-alpha, 76%, p < 0.0001), NFkappaB (86%, p < 0.001) and AP-1 (97%, p < 0.001) nuclear translocation, and IRAK-1 (87%, p < 0.001) and SAPK (80%, p < 0.001) phosphorylation. CONCLUSIONS: Lipopolysaccharide pre-treatment reduced lung injury and inflammatory mediator production after subsequent exposure to ischemia-reperfusion. Understanding the clinical significance of lipopolysaccharide in donor lungs has the potential to expand and clarify donor inclusion criteria.

Alveolar macrophage secretory products effect type 2 pneumocytes undergoing hypoxia-reoxygenation.

BACKGROUND: Activation of the alveolar macrophage is centrally important to the development of lung ischemia reperfusion injury. Alveolar macrophages and type 2 pneumocytes secrete a variety of proinflammatory mediators in response to oxidative stress. The manner in which they interact and how the macrophage may influence pneumocyte responses in lung ischemia reperfusion injury is unknown. Utilizing an in vitro model of hypoxia and reoxygenation, we sought to determine if the proinflammatory response of type 2 pneumocytes to oxidative stress would be amplified by alveolar macrophage secretory products. METHODS: Cultured pneumocytes were exposed to control media or media from cultured macrophages exposed to hypoxia and reoxygenation. Pneumocytes were subsequently subjected to hypoxia and reoxygenation and assessed for both nuclear translocation of nuclear factor kappa B and inflammatory cytokine and chemokine secretion. To examine for any reciprocal interactions, we reversed the experiment, exposing macrophages to conditioned pneumocyte media. RESULTS: In the presence of media from stimulated macrophages, production of proinflammatory mediators by type 2 pneumocytes was dramatically enhanced. In contrast, exposure of the macrophage to conditioned pneumocyte media had an inhibitory effect on macrophage responses subsequently exposed to hypoxia and reoxygenation. CONCLUSIONS: The alveolar macrophage drives the development of lung reperfusion injury in part through amplification of the inflammatory response of type 2 pneumocytes subjected to hypoxia and reoxygenation.

Noise in the ED.

BACKGROUND: The impact of noise pollution on both the patient and the care provider has been extensively studied in the neonatal intensive care unit and in other critical care units. Noise pollution makes errors more probable and is one of the risk factors for provider burnout and negative outcomes for patients. The Environmental Protection Agency (EPA) recommends that the acceptable noise level in a hospital should not exceed 40 dB. OBJECTIVES: The purpose of this study was to record and analyze noise in a large urban level I emergency department (ED) and compare to the EPA guidelines. METHODS: A 3-channel dosimeter Quest Q300 (Quest Technologies, Oconomowoc, WI) was placed as a stand-alone unit on the wall of the resuscitation booth in the ED. Sound was sampled 16 times per second for 12 hours and was recorded as peaks and averages for each minute. The dosimeter was then placed in the pocket of a medical student with a small 8-mm shoulder-mount type 2 microphone. The medical student followed an emergency medicine resident throughout an 8-hour shift in the main resuscitation area while monitoring and logging sound fluctuations in the environment. Sound pressure levels were logged in real time and subsequently correlated to the recorded peaks. Sound was sampled 16 times per second and recorded peaks and averages for each minute. RESULTS: In the initial part of the study, the time-weighted average was 43 dB. The average sound levels peaked approximately 25 times over 12 hours. Individually measured peak levels of 94 to 117 dB occurred every minute. In the second part of the study, the time-weighted average was 52.9 dB. CONCLUSIONS: When compared to EPA accepted noise levels for hospital (40 dB), the ED under study had excessive noise on a regular basis. There are easily identifiable sources of noise pollution in the ED. By identifying and modifying sources of noise, stress in the ED may be decreased.