Frozen sections in patients undergoing breast conserving surgery at a single ambulatory surgical center: 5 year experience.

OBJECTIVES: To evaluate outcomes of our breast frozen section (FS) practice in its first 5 years, including our specialized FS of margins (FSM) procedure for breast conserving therapy (BCT) patients. METHODS: One thousand two hundred and forty eight patients undergoing 1303 breast FSM and/or sentinel lymph node (SLN) FS were included. Clinicopathologic features were assessed by chart review. RESULTS: Use of SLN FS declined, from 43.5% of FS cases before to 19.2% of FS cases after 2012. FSM patients had a decline in overall reexcision to 12.3% in 2013-2014 (p = 0.063). There was also decline in reexcision for focally close margins (p < 0.0001) but no change in reexcision for extensively close margins. Reexcision was significantly associated with lobular subtype, multifocality and larger (≥T2) size. False negative FSM cases were most often influenced by extensively close or positive final (reexcised) margins sent for permanent section only (96/148; 64.9%). CONCLUSIONS: Despite changing surgical practices, FSM remains a valuable service that reduces reexcision in BCT patients.

Benefits of pulsatile flow in pediatric cardiopulmonary bypass procedures: from conception to conduction.

This review on the benefits of pulsatile flow includes not only experimental and clinical data, but also attempts to further illuminate the major factors as to why this debate has continued during the past 55 years. Every single component of the cardiopulmonary bypass (CPB) circuitry is equally important for generating adequate quality of pulsatility, not only the pump. Therefore, translational research is a necessity to select the best components for the circuit. Generation of pulsatile flow depends on an energy gradient; precise quantification in terms of hemodynamic energy levels is, therefore, a necessity, not an option. Comparisons between perfusion modes should be done after these basic steps have been taken. We have also included experimental and clinical data for direct comparisons between the perfusion modes. In addition, we included several suggestions for future clinical trials for other interested investigators.

Hemodynamic evaluation of arterial and venous cannulae performance in a simulated neonatal extracorporeal life support circuit.

OBJECTIVE: To construct an ideal extracorporeal life support (ECLS) circuit in terms of hemodynamic performance, each component of the circuit should be evaluated. Most cannulae manufacturers evaluate their products using water as the priming solution. We conducted this study to evaluate the different sizes of arterial and venous cannulae in a simulated neonatal ECLS circuit primed with human blood. METHODS: The simulated neonatal ECLS circuit was composed of a Capiox Baby RX05 oxygenator, a Rotaflow centrifugal pump and a heater & cooler unit. Three Medtronic Bio-Medicus arterial cannulae (8Fr, 10Fr, 12Fr) and three venous cannulae (10Fr, 12Fr, 14Fr) were tested in seven combinations (8A-10V, 8A-12V, 10A-10V, 10A-12V, 10A-14V, 12A-12V, 12A-14V). All the experiments were conducted using human blood at a hematocrit of 40% and at a constant temperature of 37°C. The "tip to tip" priming volume of the entire circuit was 135ml. The blood volume of the pseudo patient was 500ml. RESULTS: Flow rates increased linearly with increasing size in both venous and arterial cannulae at the same pump speeds. The increase in flow rate was greater when changing the arterial cannulae (next size larger) compared to changing the venous cannulae (next size larger). The pressure drops of the arterial cannula were correlated with the flow rates, regardless of the pseudo patient pressure and the venous cannula used simultaneously. CONCLUSIONS: The results show the difference in flow ranges and pressure drops of seven combinations of arterial and venous cannulae. It also suggests that the arterial cannula, not the venous cannula, has greater impact on the flow rate when a centrifugal pump is used in a neonatal ECLS circuit. The results of this study have been translated to further advancing the clinical practice in our institution.

Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema.

The composite physiologic index (CPI) was derived to represent the extent of fibrosis on high-resolution computed tomography (HRCT), adjusting for emphysema in patients with idiopathic pulmonary fibrosis (IPF). We hypothesised that longitudinal change in CPI would better predict mortality than forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) or diffusing capacity of the lung for carbon monoxide (D(L,CO)) in all patients with IPF, and especially in those with combined pulmonary fibrosis and emphysema (CPFE). Cox proportional hazard models were performed on pulmonary function data from IPF patients at baseline (n = 321), 6 months (n = 211) and 12 months (n = 144). Presence of CPFE was determined by HRCT. A five-point increase in CPI over 12 months predicted subsequent mortality (HR 2.1, p = 0.004). At 12 months, a 10% relative decline in FVC, a 15% relative decline in D(L,CO) or an absolute increase in CPI of five points all discriminated median survival by 2.1 to 2.2 yrs versus patients with lesser change. Half our cohort had CPFE. In patients with moderate/severe emphysema, only a 10% decline in FEV(1) predicted mortality (HR 3.7, p = 0.046). In IPF, a five-point increase in CPI over 12 months predicts mortality similarly to relative declines of 10% in FVC or 15% in D(L,CO). For CPFE patients, change in FEV(1) was the best predictor of mortality.

Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians.

SETTING: Host defense factors may influence the development of active tuberculosis (TB). OBJECTIVE: To test variants in solute carrier family 11A, member 1 (SLC11A1), for an association with TB. METHODS: A mixed case-control study of TB cases, relatives or close contact controls, consisting of 474 African-Americans (243 families) and 381 Caucasians (192 families), examined 13 SLC11A1 polymorphisms for association with pulmonary TB using generalized estimating equations adjusting for age and sex. RESULTS: Two associations were observed in Caucasians (rs3731863, P = 0.03, and rs17221959, P = 0.04) and one in African-Americans (rs3731865, P = 0.05). Multilocus analyses between polymorphisms in SLC11A1 and 11 TB candidate genes detected interactions between SLC11A1 and inducible nitric oxide synthase (NOS2A) in Caucasians (rs3731863 [SLC11A1] x rs8073782 [NOS2A], P = 0.009; rs3731863 [SLC11A1] x rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] x rs1816702, P = 0.005). CONCLUSIONS: No association was detected with 5'(GT)(n) promoter polymorphism previously associated with lower SLC11A1 expression, rs17235409 (D543N), or rs17235416 (3' TGTG insertion/deletion polymorphism). SLC11A1 polymorphism rs3731865 was associated with TB in African-Americans, consistent with previous findings in West Africans. These results suggest that variants in SLC11A1 increase susceptibility to pulmonary TB and interact with other variants that differ by race.

Challenges in pulmonary fibrosis: 6--Problematic granulomatous lung disease.

Granulomatous inflammation in lung biopsies is a relatively non-specific finding that can occur in a range of inflammatory and neoplastic conditions. This review focuses on the patterns of granulomatous inflammation that can cause diffuse lung disease, highlighting histopathological features helpful in differential diagnosis.

Modified extended end-to-end repair of coarctation in neonates and infants.

Although the classic extended end-to-end repair is the procedure of choice in most neonates and infants with coarctation of the aorta, there is a problem of distance despite extensive mobilization and impairment of growth of the arch because of scarring in some patients. Since December 1999, 15 neonates and infants without significant arch hypoplasia have undergone a modified extended end-to-end repair of coarctation of the aorta at our institution. The anastomosis was performed between the posterior wall of the isthmus and base of the subclavian artery and anterior wall of the descending aorta, resulting in an anastomosis that was usually 1(1/2) times the diameter of the descending aorta. All patients survived and were followed up to 57 months (average, 34). Two patients developed significant gradients 3 months and 1 year postoperatively, respectively, probably from luxurious tissue growth at the suture line. Both were treated successfully with balloon dilatation. The modified extended end-to-end repair provides another option for repair of coarctation in neonates and infants. It requires less mobilization of the arch and descending aorta. It is particularly useful in patients with long isthmus.

Citrullination in extra-articular manifestations of rheumatoid arthritis.

BACKGROUND: Anti-citrullinated protein antibodies have been detected with high specificity in serum of patients with rheumatoid arthritis (RA), and citrullination of proteins may play a key role in the pathogenesis of RA. We therefore investigated the presence of citrullination in two extra-articular manifestations of RA, interstitial pneumonia (IP) and rheumatoid nodules. METHODS: Open-lung biopsy specimens from patients with RA-associated IP (n = 18), idiopathic IP (n = 20) and controls (n = 10), as well as specimens of rheumatoid nodules from 26 patients, were examined. All sections were incubated with an anti-modified citrulline antibody. Masked scoring of stained sections and analysis of results by stratification according to demographic and clinical characteristics was performed. RESULTS: Presence of citrulline could be detected in eight lung specimens of patients with RA-associated IP (44%) and nine patients with idiopathic IP (46%). Conversely, lung tissue from control patients showed weak extracellular citrullination in only two cases (20%). Citrullination did not show any significant associations with demographic or clinical characteristics such as age, gender, smoking habits, disease severity, histological subtype, degree of inflammation or steroid use. Rheumatoid nodules were citrulline positive in a majority of cases (70%). CONCLUSION: Citrullination is present in extra-articular manifestations of RA such as IP and nodules. In contrast to the high specificity of anti-citrulline antibodies in RA, citrullination is not only restricted to RA but can also be observed in idiopathic IP. Whether citrullination significantly contributes to the initiation or perpetuation of autoimmunity or merely reflects ongoing inflammation remains to be clarified.

Morphological and quantitative assessment of mast cells in rheumatoid arthritis associated non-specific interstitial pneumonia and usual interstitial pneumonia.

BACKGROUND: The role of mast cells in extra-articular manifestations of rheumatoid arthritis (RA) has not been studied so far. OBJECTIVE: To characterise and quantify mast cells in RA associated interstitial pneumonia (IP) by an immunohistological study. METHODS: Lung biopsy specimens from 15 patients with RA associated IP, 12 patients with idiopathic IP, and 5 control patients were stained with antibodies directed against tryptase (mast cell marker). Morphological characterisation of stained specimens was carried out and staining was quantified by computer assisted image analysis. RESULTS: Tryptase staining showed the marked presence of mast cells in idiopathic IP and in RA associated IP. A significant difference in stained tissue area was found between RA associated IP (2.6%, IQR 2.0-3.2%, p = 0.015) and idiopathic IP (3.1%, IQR 1.8-3.7%, p = 0.003) compared with control tissue specimens (1.0%, IQR 0.7-1.5%). The extent of mast cell infiltration correlated well and inversely with pulmonary function variables. CONCLUSIONS: Mast cell infiltrates are present in RA associated IP and idiopathic IP. The observed correlation of pulmonary function and mast cell numbers would be consistent with the proposed role of mast cell mediators in the promotion of fibrogenesis. The findings provide a rationale for studying functional aspects of mast cell involvement in the pathogenesis of RA associated lung disease.

Pulmonary artery growth fails to match the increase in body surface area after the Fontan operation.

OBJECTIVE: To evaluate the growth of the pulmonary arteries after a Fontan procedure. DESIGN: Retrospective review. SETTING: Two paediatric cardiology tertiary care centres. PATIENTS: 61 children who underwent a modified Fontan operation and had angiography suitable for assessment of pulmonary artery size before the Fontan procedure and during long term follow up. An atriopulmonary connection (APC) was present in 23 patients (37.7%) and a total cavopulmonary connection (TCPC) was present in 38 (62.3%). Postoperative angiograms were performed 0.5-121 months (median 19 months) after the Fontan operation. MAIN OUTCOME MEASURE: Growth of each pulmonary artery measured just before the first branching point. The diameter was expressed as a z score with established nomograms used to standardise for body surface area. RESULTS: The mean change in the preoperative to postoperative z scores of the right pulmonary artery was -1.06 (p = 0.004). The mean change in the preoperative to postoperative z scores of the left pulmonary artery was -0.88 (p = 0.003). Changes in the preoperative to postoperative z scores were more pronounced in the patients undergoing APC than TCPC, especially for the right pulmonary artery. CONCLUSION: After the Fontan operation, growth of the pulmonary arteries often fails to match the increase in body surface area.

Right ventricular outflow tract transannular patch placement without cardiopulmonary bypass.

In children with pulmonary atresia not amenable to initial complete correction, antegrade pulmonary blood flow can be established with surgical right ventricular outflow tract (RVOT) patch enlargement. An 11-year experience with RVOT transannular patch (TAP) augmentation without the use of cardiopulmonary bypass (off-pump) is reported. From March 1993 to October 2004, off-pump surgical RVOT enlargement with a TAP was attempted in all patients in whom a concurrent procedure that required bypass was not required. The procedure was performed with cardiopulmonary bypass standby. Twenty-two consecutive patients in whom this procedure was attempted were reviewed. Twenty of 22 patients tolerated off-pump TAP placement. In 2 patients with ductal-dependent pulmonary blood flow, off-pump TAP placement was not tolerated. Adequate antegrade pulmonary blood flow was achieved in all patients without operative mortalities or complications. There was one death in the postoperative period from myocardial ischemia secondary to right ventricular-dependent coronary circulation. Transannular RVOT patch augmentation can be performed safely and effectively without cardiopulmonary bypass.

Field test results of an automated exposure assessment tool, the local positioning system (LPS).

A user-friendly environmental monitoring system that collects real time data has been developed. Flash card memory logs exposure data from multiple sensors along with corresponding times and positions. Optional use of telemetry repeaters and a reference station allows central monitoring of data to assess exposure and to initiate intervention when safe levels are exceeded. A software analysis package allows researchers to identify exposure hot spots and direct control efforts, with the ultimate goal being to reduce injury and disease. Preliminary field test results document position accuracy and system performance in harsh environments.

Intraoperative transesophageal echocardiography in a 1.4-kg infant with complex congenital heart disease.

The lower weight limit for infants undergoing intraoperative transesophageal echocardiography (TEE) with current commercially available probes has not been determined. A review of the literature reveals that infants as small as 1.6 kg have been studied successfully. This report describes the first intraoperative TEE reported in a 1.4-kg infant during truncus arteriosus/interrupted aortic arch repair. Successful pre- and postoperative images of the cardiac abnormality were obtained. Probe insertion was performed in this small patient after predilating the esophagus with a 14-F suction catheter.

Metastatic angiosarcoma masquerading as diffuse pulmonary hemorrhage: clinicopathologic analysis of 7 new patients.

CONTEXT: Diffuse pulmonary hemorrhage is an uncommon presenting manifestation of angiosarcoma. OBJECTIVE: To review the clinical, radiologic, and pathologic findings of patients with metastatic angiosarcoma who presented with diffuse pulmonary hemorrhage. DESIGN: Patients fulfilling inclusion criteria were identified from the consultation files. Clinical and radiologic data were obtained from referring pathologists. Histologic slides were reviewed in all patients. RESULTS: Our patients included 6 men and 1 woman, aged 31 to 73 years; 4 patients were younger than 40 years. Six patients presented with hemoptysis, and all had diffuse abnormalities on radiographic studies. Clinical considerations prior to biopsy included pulmonary hemorrhage syndrome (n = 2), acute respiratory failure (n = 1), and infection (n = 1). Metastatic disease was included in the differential diagnosis in only 1 patient. None had a diagnosis of malignancy prior to lung biopsy. All biopsies showed hemorrhage associated with atypical epithelioid and spindle cells, forming anastomosing vascular channels, distributed along and within lymphatics and arteries. Neoplastic cells were immunoreactive for factor VIII-related protein or CD31 in all cases for which special stains were available. Three patients with complete follow-up died of their disease. Primary sites were discovered in all 3 patients who underwent autopsy examination. Two tumors arose in the heart and 1 in the pelvic soft tissues. One additional patient had a likely primary site identified in the right atrium by cardiac ultrasound and was subsequently lost to follow-up. CONCLUSION: Angiosarcoma should be included in the differential diagnosis of diffuse pulmonary hemorrhage, especially in young adults.

DNA mismatch repair genes hMLH1, hMSH2, and hMSH6 are not inactivated in bronchioloalveolar carcinomas of the lung.

BACKGROUND: Defective DNA mismatch repair (MMR) appears to be rare in nonsmall cell carcinomas of the lung. Defective DNA MMR results from genetic or epigenetic alterations that inactivate the DNA MMR genes hMLH1 or hMSH2, and rarely hMSH6. The loss of normal DNA MMR is thought to promote tumorigenesis by accelerating the accumulation of mutations in oncogenes and tumor suppressor genes. Inactivation of hMLH1, hMSH2, and hMSH6 is observed as a loss of expression of these proteins by immunohistochemistry. Bronchioloalveolar carcinoma is a subtype of adenocarcinoma with distinctive clinical and pathologic features. MATERIALS AND METHODS: An immunohistochemical study was performed on paraffin embedded sections of 33 bronchioloalveolar carcinomas (20 nonmucinous and 13 mucinous) for hmlh1, hmsh2, and hmsh6 proteins. RESULTS All the tumors showed normal expression of hmlh1, hmsh2, and hmsh6. CONCLUSIONS: These findings suggest that defective DNA MMR due to inactivation of hMLH1, hMSH2, or hMSH6 does not play a significant role in the pathogenesis of bronchioloalveolar carcinomas.

Aortopulmonary size discrepancy is not a contraindication to the pediatric Ross operation.

BACKGROUND: Modification of the aortic annulus or the ascending aorta, or both, may be required in pediatric patients undergoing the Ross operation. The fate of these autografts remains uncertain. METHODS: Retrospective review of 15 patients undergoing Ross operation without aortic annular modification (group 1), 11 patients requiring annular reduction (group 2, n = 11), and 8 patients requiring annular enlargement (group 3, n = 8). Autograft function and dimensions were evaluated by echocardiography. RESULTS: Autograft insufficiency was less than or equal to mild in 33 patients and moderate in 1 patient. The annulus body surface area ratio increased in group 1 from 19.7 +/- 5 to 20.3 +/- 5 mm/M2 (p = 0.8). The average annular reduction in group 2 was 5 +/- 1.5 mm, and 10 of 11 patients required reduction of the ascending aorta (mean 11 +/- 5 mm). The annulus body surface area ratio increased from 18.6 +/- 7 to 20.5 +/- 9 mm/M2 (p = 0.2). The mean augmentation in annulus diameter in group 3 was 6 +/- 4 mm; the annulus body surface area ratio decreased from 23.7 +/- 14 to 20.3 +/- 8 mm/M2 (p = 0.5). CONCLUSIONS: We continue to offer the Ross operation to pediatric patients even when aortic annular or ascending aortic size discrepancies mandate surgical modifications.

Efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

PURPOSE: To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. PATIENTS AND METHODS: We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy. RESULTS: Of the 745 women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%). CONCLUSION: The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

Accessibility of potential referents following categorical anaphors.

In 4 experiments, the authors investigated the accessibility of potential antecedents that were either referents or nonreferents of categorical anaphors using several methodologies. In 2 preliminary experiments, using an immediate probe recognition task, the authors replicated previous findings of inhibition for nonreferents following categorical anaphors. In Experiments 1-3, naming times to nonreferent probes were inhibited, but only at a delay and at the end of the sentence. Eye movements were monitored in Experiment 4, and reading times were found to be slower in end-of-sentence regions following the remention of the nonreferent but not on the nonreferent itself. These results suggest that decreases in nonreferent accessibility are due to postanaphoric processes, such as integrating the nonreferent into the discourse structure, and are not due to more immediate changes in activation occurring as part of the resolution process. Further, some inhibition effects may result from the use of probe tasks that require decisions.

Pathologic and clinical features of primary pulmonary extranodal marginal zone B-cell lymphoma of MALT type.

We reviewed pathologic, phenotypic, and clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type primarily involving lung to address unresolved questions regarding behavior and pathologic features of unambiguously diagnosed pulmonary MALT lymphoma. Lung specimens from 50 patients were reviewed. Forty-one had low-grade MALT lymphoma. Nine had low-grade MALT lymphoma and diffuse large B-cell lymphoma. The patients included 32 women and 18 men with a median age of 68 years (range 34-88 years). Half of the patients were asymptomatic at the time lymphoma was diagnosed. Radiographic abnormalities were more commonly unilateral (37 patients) than bilateral (12 patients). Localized masses or nodules occurred in 39 patients. Associated autoimmune disorders (29%) and monoclonal gammopathies (43%) were common. Low-grade lymphomas formed intraparenchymal masses composed of centrocyte-like cells, plasmacytoid lymphocytes, and plasma cells that formed lymphoepithelial lesions and exhibited a lymphangitic growth pattern. Mediastinal lymph nodes were involved histologically in 44% of cases. Lymphoma-specific survival was 71.7% at 10 years, and overall survival was significantly worse than age-and gender-matched control patients. None of the following features predicted those patients who had an adverse outcome: systemic symptoms, presence of autoimmune disorders or paraproteinemia, anatomic distribution and number of pulmonary lesions, lymph node involvement, or presence of anthracycline-treated large B-cell lymphoma.