Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes fails to predict breast cancer recurrence: a final analysis of a prospective multi-institutional cohort study.

BACKGROUND: To address the clinical relevance of molecular detection of occult breast cancer in sentinel lymph nodes and nonsentinel axillary lymph nodes (ALN), we initiated the Minimally Invasive Molecular Staging of Breast Cancer (MIMS) trial, a multi-institutional prospective cohort study. This trial represents the first prospective cohort study in which a multimarker, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was applied to the detection of breast cancer micrometastases in ALN. MATERIALS AND METHODS: Sentinel and/or nonsentinel ALN from 501 breast cancer subjects with T1-T3 primary tumors were analyzed by standard histopathology and multimarker, real-time RT-PCR analysis. Seven breast cancer-associated genes (mam, mamB, PIP, CK19, muc1, PSE, and CEA) known to be overexpressed in metastatic breast cancer compared with control lymph nodes were used. Follow-up data were collected for 5 years. RESULTS: Of the 501 breast cancer subjects enrolled, 348 were node negative and completed the 5-year follow-up. Of these patients (n = 94), 27% demonstrated evidence of molecular overexpression. The 5-year relapse-free survival rate was 95.4% (95% confidence interval [95% CI], 92.4-97.2%). No single gene or combination of study genes was predictive of recurrence. CONCLUSIONS: The genes in this study panel failed to be predictive of clinical relapse. This may be a function of several factors: the low event rate at 5 years, the particular gene set, the methodology used for detection/analysis or that our original hypothesis was wrong and that the presence of positive marker signal by real-time RT-PCR is not associated with a worsened clinical outcome.

Triage and trauma workload in mass casualty: a computer model.

BACKGROUND: The aim of this study was to quantitatively analyze the impact of hospital triage on the workload of trauma teams in the Emergency Department during a mass casualty incident, using a computer model. METHODS: The inflow and triage of casualties into an Emergency Department with 5 trauma teams was modeled using the Monte Carlo method. Triage was represented as a binary classification task performed in one or two sequential steps. The input variables were triage accuracy (specificity and sensitivity) and casualty load, and the key output variable was the time to saturation (TTS) of the trauma teams, which was computed from the available and needed team minutes. RESULTS: The relationship between an increasing casualty load and the TTS describes a sigmoid-shaped curve. Improving triage accuracy extends the TTS and shifts the curve to the right. Switching to sequential competent triage (80% accuracy) results in TTS that is similar to perfect single-step triage (100% accuracy) but at the cost of investing less team time in urgent casualties. The optimal ratio of trauma teams to urgent casualties in sequential mode is 1:8, indicating that the treatment of urgent casualties must be delegated to reinforcement staff. CONCLUSIONS: This study introduces innovative tools for quantitative analysis of hospital triage in mass casualty incidents and shows how triage accuracy and mode affect the ability of trauma teams to cope with heavy casualty loads. These tools can be used to optimize the hospital response to future threats.

Best practice determination of timing of spinal fracture fixation as defined by analysis of the National Trauma Data Bank.

BACKGROUND: To examine the efficacy of early versus late spinal fracture fixation, we reviewed National Trauma Data Bank (NTDB) records to identify the breakpoint in reported timing of operative fixation. Using this breakpoint we then analyzed outcome for those treated early versus late, hypothesizing that the early group would experience better outcome as reflected by resource utilization and complications. METHODS: The NTDB was queried for patients with any level spinal fracture that required surgical stabilization. Histogram analysis of the postinjury day of initial operative fixation was used to determine the point at which the majority of operative procedures had been performed, thereby defining early (E) and late (L) groups. Patients in E were matched to a cohort from L with similar age, Injury Severity Score, and Glasgow Coma Scale. Outcome data included hospital length of stay, intensive care unit length of stay, ventilator days, charges, incidence of complications, and mortality. The groups were compared using Student's t test for continuous variables and Fisher's exact test for categorical variables, accepting p < or = 0.05 as significant. RESULTS: Of 16,812 patients who underwent operative fixation, 59% were completed within 3 days of injury and formed E. The 374 L patients whose dataset was complete enough to allow analysis were matched to 497 E patients. There was no significant difference in the presence of spinal cord injury between E and L (51 vs. 48%; p = 0.3735). Complications were significantly higher in L (30% vs. 17.5%; p < 0.0001) yet mortality was similar in both groups (2.0% vs.1.9%; p > 0.05). CONCLUSIONS: NTDB records indicate that the majority of patients with spinal fractures undergo operative fixation within 3 days, and that these patients had less complications and required less resources. Use of a national data bank to compare groups with similar injury severity and presenting physiology can validate best practice and define opportunities for improvement in care.

Definitive establishment of airway control is critical for optimal outcome in lower cervical spinal cord injury.

BACKGROUND: Respiratory complications can undermine outcome from low cervical spinal cord injury (SCI) (C5-T1). Most devastating of these is catastrophic loss of airway control. This study sought to determine the incidence and effect of catastrophic airway loss (CLA) and to define the need for elective intubation with subsequent tracheostomy to prevent potentially fatal outcomes. METHODS: A database of 54,838 consecutive patients treated in a level I trauma center between January 1988 and December 2004 was queried to identify patients with low cervical SCI, without traumatic brain injury. Patients were then stratified into complete or incomplete SCI groups, based on clinical assessment of their SCI. Mortality, age, injury severity, need for intubation, and tracheostomy were analyzed for each group using Fisher's exact test or Student's t test, as appropriate, accepting p < 0.05 as significant. RESULTS: One hundred eighty-six patients met inclusion criteria. The majority of low cervical spinal cord injuries were complete (58%). Overall, 127 (68%) patients required intubation, 88 (69%) required tracheostomy, and 27 died (15% of study population). Between each group there were significant differences in age and Injury Severity Score, however, within each group there were no significant differences in either. Eleven CSCI patients were not intubated; four of whom were at family request. Six of the remaining seven patients encountered fatal catastrophic airway loss. One patient was discharged to rehabilitation. Patients with incomplete SCI required intubation less frequently (38%); however, 50% of those required tracheostomy for intractable pulmonary failure. CONCLUSIONS: These data indicate that regardless of severity of low cervical SCI, immediate, thorough evaluation for respiratory failure is necessary. Early intubation is mandatory for CSCI patients. For incomplete patients evidence of respiratory failure should prompt immediate airway intervention, half of whom will require tracheostomy.

The effect of early surgical treatment of traumatic spine injuries on patient mortality.

INTRODUCTION: The ideal timing of spinal fixation is controversial. A recent study showed that early spine fixation reduced morbidity and resource utilization. We previously noted a trend toward higher mortality in patients undergoing early spinal fixation. This study was done to analyze whether the timing of spinal fixation had a significant effect on mortality. METHODS: The registry of our Level I trauma program was queried for all patients with at least one spinal vertebral injury. Anatomic and physiologic variables included age, initial Glasgow Coma Scale score, systolic blood pressure, heart rate, and Injury Severity Score. Outcome was evaluated in terms of ventilator days, intensive care unit length of stay, hospital length of stay (HLOS), and mortality. Patients were stratified by day of spinal operative fixation as early when done within 48 hours and late when done after 48 hours. Data were analyzed using chi and an unpaired t test, accepting p < 0.05 as significant. RESULTS: Three hundred sixty-one patients between January 1988 and February 2003 required operative spinal fixation (158 early, within 48 hours vs. 203 late, beyond 48 hours). There was no significant difference between the two groups except mortality, which was significantly higher in the early group (7.6 vs. 2.5%; p = 0.0257), and HLOS, which was significantly shorter in the early group (14.42 vs. 17.64 days; p = 0.025). CONCLUSION: Spinal fixation within 48 hours after vertebral fractures and dislocations appears to increase mortality despite similar anatomic and physiologic parameters in the later operative group. Incomplete resuscitation of patients before surgery may have contributed to this result. The shorter HLOS may have been because of the higher number of early deaths. Prospective studies to identify the optimal timing of spinal fixation and the reason for these outcome differences are warranted.

Disasters and mass casualties: I. General principles of response and management.

Disaster planning and response to a mass casualty incident pose unique demands on the medical community. Because they would be required to confront many casualties with bodily injury and surgical problems, surgeons in particular must become better educated in disaster management. Compared with routine practice, triage principles in disasters require an entirely different approach to evaluation and care and often run counter to training and ethical values. An effective response to disaster and mass casualty events should focus on an "all hazards" approach, defined as the ability to adapt and apply fundamental disaster management principles universally to any mass casualty incident, whether caused by people or nature. Organizational tools such as the Incident Command System and the Hospital Incident Command System help to effect a rapid and coordinated response to specific situations. The United States federal government, through the National Response Plan, has the responsibility to respond quickly and efficiently to catastrophic incidents and to ensure critical life-saving assistance. International medical surgical response teams are capable of providing medical, surgical, and intensive care services in austere environments anywhere in the world.

Disasters and mass casualties: II. explosive, biologic, chemical, and nuclear agents.

Terrorists' use of explosive, biologic, chemical, and nuclear agents constitutes the potential for catastrophic events. Understanding the unique aspects of these agents can help in preparing for such disasters with the intent of mitigating injury and loss of life. Explosive agents continue to be the most common weapons of terrorists and the most prevalent cause of injuries and fatalities. Knowledge of blast pathomechanics and patterns of injury allows for improved diagnostic and treatment strategies. A practical understanding of potential biologic, chemical, and nuclear agents, their attendant clinical symptoms, and recommended management strategies is an important prerequisite for optimal preparation and response to these less frequently used agents of mass casualty. Orthopaedic surgeons should be aware of the principles of management of catastrophic events. Stress is less an issue when one is adequately prepared. Decontamination is essential both to manage victims and prevent further spread of toxic agents to first responders and medical personnel. It is important to assess the risk of potential threats, thereby allowing disaster planning and preparation to be proportional and aligned with the actual casualty event.

To nearly come full circle: Nonoperative management of high-grade IV-V blunt splenic trauma is safe using a protocol with routine angioembolization.

INTRODUCTION: Nonoperative management (NOM) of hemodynamically stable high-grade (IV-V) blunt splenic trauma remains controversial given the high failure rates (19%) that persist despite angioembolization (AE) protocols. The NOM protocol was modified in 2011 to include mandatory AE of all grade (IV-V) injuries without contrast blush (CB) along with selective AE of grade (I-V) with CB. The purpose of this study was to determine if this new AE (NAE) protocol significantly lowered the failure rates for grade (IV-V) injuries allowing for safe observation without surgery and if the exclusion of grade III injuries allowed for the prevention of unnecessary angiograms without affecting the overall failure rates. METHODS: The records of patients with blunt splenic trauma from January 2000 to October 2014 at a Level I trauma center were retrospectively reviewed. Patients were divided into two groups and failure of NOM (FNOM) rates compared: NAE protocol (2011-2014) with mandatory AE for all grade (IV-V) injuries without CB and selective AE for grade (I-V) with CB versus old AE (OAE) protocol (2000-2010) with selective AE for grade (I-V) with CB. RESULTS: Seven hundred twelve patients underwent NOM with 522 (73%) in the OAE group and 190 (27%) in the NAE group. Evolving from the OAE to the NAE strategy resulted in a significantly lower FNOM rate for the overall group (grade I-V) (OAE vs. NAE, 4% to 1%, p = 0.04) and the grade (IV-V) group (OAE vs. NAE, 19% vs. 3%, p = 0.01). Angiograms were avoided in 113 grade (I-III) injuries with no CB; these patients had NOM with observation alone and none failed. CONCLUSIONS: A protocol using mandatory AE of all high-grade (IV-V) injuries without CB and selective AE of grade (I-V) with CB may provide for optimum salvage with safe NOM of the high-grade injuries (IV-V) and limited unnecessary angiograms. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Popliteal vascular injuries.

Popliteal vascular injury remains one of the most difficult diagnostic and therapeutic challenges for trauma surgeons. Only with strict attention to rapid diagnosis; early surgical treatment with meticulous technical skill; and aggressive use of various adjunctive measures, such as completion arteriography, anticoagulation, fasciotomy, and proper prioritization of management of multiple injuries, can limb salvage be optimized.

Lobular Carcinoma In Situ of the Breast.

LCIS was first described in 1941 as a distinct pathologic entity by Foote and Stewart who called it a "rare form of mammary carcinoma." It is thought to represent a transitional intra-epithelial, or in situ, stage in the evolution of breast cancer from hyperplastic breast epithelium. With the wide application of mammography, its detection has increased in recent years, being found in approximately 1% of all breast biopsy specimens and 5% of all breast malignancies. Its true incidence is unknown, because the absence of any clinical or radiographic manifestations makes its detection completely arbitrary and random. LCIS has distinct pathologic features characterized by proliferation of bland, homogeneous malignant cells within the terminal duct-lobular apparatus. The lobular architecture and investing basement membrane remain intact with no evidence of invasion into the surrounding stoma. It is assumed to be widely disseminated throughout all breast tissue whenever it is found, having close to 100% incidence of multicentricity and bilaterality. The cells are typically of low histologic and nuclear grade, highly estrogen receptor positive, and have tumor marker characteristics of indolent growth and good prognosis. This is very different from its noninvasive ductal counterpart, DCIS, which is typified by more aggressive cytologic and biologic characteristics. Although LCIS imparts as much as a 12-fold increased risk of subsequent invasive breast carcinoma, its natural history suggests it is more of a marker of risk rather than a true premalignant lesion. Most subsequent malignancies occur more than 15 years after diagnosis, and are ductal rather than lobular. This risk is also equally applied to both breasts, regardless of which breast contains the diagnosed focus. Subsequent invasive breast cancers are typically early with very low mortality, most likely due to the strict mammographic surveillance provided to these women. Although originally treated by mastectomy, most now manage LCIS by careful non-operative observation, in the same way that other risk factors such as family history or atypical hyperplasia are managed. In fact, it has been questioned whether there should be any real distinction between lobular hyperplasia and LCIS. There is no role for excision of biopsy sites of LCIS to obtain clear margins, nor for cytotoxic chemotherapy. However, the NSABP P-1 Prevention Trial strongly suggests that subsequent risk can be significantly reduced by tamoxifen. The only rational surgical treatment, if ablation is judged necessary, would be bilateral mastectomy, which appears far too aggressive in view of its low overall risks. Further investigation should clarify the optimal management of LCIS.

More harm than good: antiseizure prophylaxis after traumatic brain injury does not decrease seizure rates but may inhibit functional recovery.

BACKGROUND: The purposes of this study were to examine the current Brain Trauma Foundation recommendation for antiseizure prophylaxis with phenytoin during the first 7 days after traumatic brain injury (TBI) in preventing seizures and to determine if this medication affects functional recovery at discharge. METHODS: The records of adult (age ≥ 18 years) patients with blunt severe TBI who remained in the hospital at least 7 days after injury were retrospectively reviewed from January 2008 to January 2010. Clinical seizure rates during the first 7 days after injury and functional outcome at discharge were compared for the two groups based on antiseizure prophylaxis, no prophylaxis (NP) versus phenytoin prophylaxis (PP). Statistical analysis was performed using χ2. RESULTS: A total of 93 adult patients who met the previously mentioned criteria were identified (43 [46%] NP group vs. 50 [54%] PP group). The two groups were well matched. Contrary to expectation, more seizures occurred in the PP group as compared with the NP group; however, this did not reach significance (PP vs. NP, 2 [4%] vs. 1 [2.3%], p = 1). There was no significant difference in the two groups (PP vs. NP) as far as disposition are concerned, mortality caused by head injury (4 [8%] vs. 3 [7%], p = 1), discharge home (16 [32%] vs. 17 [40%], p = 0.7), and discharge to rehabilitation (30 [60%] vs. 23 [53%], p = 0.9). However, with PP, there was a significantly longer hospital stay (PP vs. NP, 36 vs. 25 days, p = 0.04) and significantly worse functional outcome at discharge based on Glasgow Outcome Scale (GOS) score (PP vs. NP, 2.9 vs. 3.4, p < 0.01) and modified Rankin Scale score (2.3 ± 1.7 vs. 3.1 ± 1.5, p = 0.02). CONCLUSION: PP may not decrease early posttraumatic seizure and may suppress functional outcome after blunt TBI. These results need to be verified with randomized studies before recommending changes in clinical practice and do not apply to penetrating trauma. LEVEL OF EVIDENCE: Therapeutic study, level IV; epidemiologic study, level III.

At first blush: absence of computed tomography contrast extravasation in Grade IV or V adult blunt splenic trauma should not preclude angioembolization.

BACKGROUND: To clarify the role, indications, and outcomes for angioembolization (AE) of nonoperatively managed (NOM) splenic trauma, the implications of absent contrast blush (CB) on computed tomography of high-grade (IV-V) blunt splenic trauma (BST) in adults were analyzed. METHODS: All BST patients presenting at a single institution from July 2000 to December 2011 were retrospectively reviewed. Grade of injury (American Association for the Surgery of Trauma scale), CB on initial computed tomography, numbers of NOM and undergoing AE, and failures of NOM were analyzed. Statistical analysis was performed using χ(2). RESULTS: Of the 1,056 total BST patients, 556 (64%) were hemodynamically stable and eligible for NOM; 95 NOM patients (17%) had CB. AE was performed in 88 of these, with angiographic extravasation found in 86 (97.7%), and 3 of these 88 (3.4%) failed NOM. The remaining 7 CBs were observed without AE, of which 5 (71.4%) failed NOM (p = 0.0004). Of all 556 NOM patients, 51 (9.5%) had high-grade injuries without CB; 20 of these (39%) underwent AE, 17 (85.0%) underwent angiographic extravasation, and there were no NOM failures in this group. The other 31 high-grade injuries without CB or AE had 8 failures of NOM (26%) (p = 0.03). CONCLUSION: The strong correlation of CB with active bleeding on angiogram mandates AE for CB in all BST undergoing NOM. However, the absence of CB in high-grade (IV-V) BST does not reliably exclude active bleeding. This may be the reason for the high reported failure rates of NOM in high-grade (IV-V) BST because AE is not typically performed in the absence of CB. These data suggest that all hemodynamically stable high-grade (IV-V) BST in adults should undergo AE regardless of CB to optimize the success and safety of NOM. LEVEL OF EVIDENCE: Therapeutic study, level III.

Evaluation and management of penetrating lower extremity arterial trauma: an Eastern Association for the Surgery of Trauma practice management guideline.

BACKGROUND: Extremity arterial injury after penetrating trauma is common in military conflict or urban trauma centers. Most peripheral arterial injuries occur in the femoral and popliteal vessels of the lower extremity. The Eastern Association for the Surgery of Trauma first published practice management guidelines for the evaluation and treatment of penetrating lower extremity arterial trauma in 2002. Since that time, there have been advancements in the management of penetrating lower extremity arterial trauma. As a result, the Practice Management Guidelines Committee set out to develop updated guidelines. METHODS: A MEDLINE computer search was performed using PubMed (www.pubmed.gov). The search retrieved English language articles regarding penetrating lower extremity trauma from 1998 to 2011. References of these articles were also used to locate articles not identified through the MEDLINE search. Letters to the editor, case reports, book chapters, and review articles were excluded. The topics investigated were prehospital management, diagnostic evaluation, use of imaging technology, the role of temporary intravascular shunts, use of tourniquets, and the role of endovascular intervention. RESULTS: Forty-three articles were identified. From this group, 20 articles were selected to construct the guidelines. CONCLUSION: There have been changes in practice since the publication of the previous guidelines in 2002. Expedited triage of patients is possible with physical examination and/or the measurement of ankle-brachial indices. Computed tomographic angiography has become the diagnostic study of choice when imaging is required. Tourniquets and intravascular shunts have emerged as adjuncts in the treatment of penetrating lower extremity arterial trauma. The role of endovascular intervention warrants further investigation.

Selective angiographic embolization of blunt splenic traumatic injuries in adults decreases failure rate of nonoperative management.

BACKGROUND: To determine whether angioembolization (AE) in hemodynamically stable adult patients with blunt splenic trauma (BST) at high risk for failure of nonoperative management (NOM) (contrast blush [CB] on computed tomography, high-grade IV-V injuries, or decreasing hemoglobin) results in lower failure rates than reported. METHODS: The records of patients with BST from July 2000 to December 2010 at a Level I trauma center were retrospectively reviewed using National Trauma Registry of the American College of Surgeons. Failure of NOM (FNOM) occurred if splenic surgery was required after attempted NOM. Logistic regression analysis was used to identify factors associated with FNOM. RESULTS: A total of 1,039 patients with BST were found. Pediatric patients (age <17 years), those who died in the emergency department, and those requiring immediate surgery for hemodynamic instability were excluded. Of the 539 (64% of all BST) hemodynamically stable patients who underwent NOM, 104 (19%) underwent AE and 435 (81%) were observed without AE (NO-AE). FNOM for the various groups were as follows: overall NOM (4%), NO-AE (4%), and AE (4%). There was no significant difference in FNOM for NO-AE versus AE for grades I to III: grade I (1% vs. 0%, p = 1), grade II (2% vs. 0%, p = 0.318), and grade III (5% vs. 0%, p = 0.562); however, a significant decrease in FNOM was noted with the addition of AE for grades IV to V: grade IV (23% vs. 3%, p = 0.04) and grade V (63% vs. 9%, p = 0.03). Statistically significant independent risk factors for FNOM were grade IV to V injuries and CB. CONCLUSION: Application of strictly defined selection criteria for NOM and AE in patients with BST resulted in one of the lowest overall FNOM rates (4%). Hemodynamically stable BST patients are candidates for NOM with selective AE for high-risk patients with grade IV to V injuries, CB on initial computed tomography, and/or decreasing hemoglobin levels. LEVEL OF EVIDENCE: III, therapeutic study.

Age does not affect outcomes of nonoperative management of blunt splenic trauma.

BACKGROUND: The purpose of this study was to examine the effect of age on the outcomes of nonoperative management (NOM) of blunt splenic trauma (BST). STUDY DESIGN: The records of patients with BST, from July 2000 to December 2010 at a level I trauma center, were retrospectively reviewed using NTRACS (National Trauma Registry of the American College of Surgeons). Patients were divided into 2 age groups: 17 to 55 years and greater than 55 years. Stepwise logistic regression analysis was used to identify risk factors associated with failure of nonoperative management (FNOM). RESULTS: There were 539 hemodynamically stable patients with BST who underwent NOM. Of these, 459 were age 55 or less, and 80 were greater than 55. Overall, there was no significant difference in FNOM rate for patients age 55 or less vs greater than 55 (4% vs 5%, p = 0.73). This also held true when FNOM was analyzed by each grade: I (1% vs 3%, p = 0.38), II (2% vs 0%, p = 1.0), III (4% vs 0%, p = 1.0), IV (8% vs 20%, p = 0.33), and V (21% vs 50%, p = 0.47). The addition of angioembolization (AE) to high grade IV to V injuries significantly lowered the FNOM rate: age 55 or less (6% AE vs 28% NO-AE, p = 0.02); with a trend toward significance for age greater than 55 (0% AE vs 60% NO-AE, p = 0.2). Age was not a statistically significant independent risk factor for FNOM (p = 0.37). CONCLUSIONS: Age does not affect outcomes of NOM of BST. High grade (IV to V) injuries are not a contraindication to NOM for patients older than 55. As experience with AE grows in patients with high grade injury and age greater than 55, it may prove to be a valuable adjunct to NOM in this group of patients.