A multi-institutional analysis of intraoperative radiotherapy for early breast cancer: Does age matter?

BACKGROUND: Single-session intraoperative radiation therapy (IORT) minimizes treatment demands associated with traditional whole breast radiation therapy (WBRT) but outcomes on local disease control and morbidity among the elderly is limited. METHODS: A multi-institutional retrospective registry was established from 19 centers utilizing IORT from 2007 to 2013. Patient, tumor, and treatment variables were analyzed for ages <70 and ≥70. RESULTS: We evaluated 686 patients (<70 = 424; ≥70 = 262) who were margin and lymph node negative. Patients <70 were more likely to have longer operative time, oncoplastic closure, higher rates of IORT used as planned boost, and receive chemotherapy and post-operative WBRT. Wound complication rates were low and not significantly different between age groups. Median follow-up was 1.06 (range 0.51-1.9) years for < 70 and 1.01 (range 0.5-1.68) years for ≥ 70. There were 5 (0.73%) breast recurrences (4 in <70 and 1 ≥ 70, p = 0.65) and no axillary recurrences during follow-up. CONCLUSIONS: IORT was associated with a low rate of wound complication and local recurrence on short-term follow-up in this cohort.

Attenuation of cue-induced smoking urges and brain reward activity in smokers treated successfully with bupropion.

Twenty-two regular smokers (15+ cigarettes per day) were treated with bupropion and group therapy for 2 months. Subjects underwent positron emission tomography (PET) studies using measures of brain global and regional glucose metabolism (regional cerebral metabolic rates of glucose [rCMRglc]) with [18F]-Fluorodeoxyglucose (FDG) twice, after watching a videotape showing smoking scenes and after watching a control movie in counter-balanced order. A questionnaire of smoking urges (QSU) was filled in before and after watching both the movies. Changes in brain metabolic rates of FDG were analysed using Statistical Parametric Maps (SPM 2) in 11 smokers who abstained from smoking in comparison with 11 smokers who continued to smoke during the second month of treatment. Still-smokers had higher craving scores after watching the videotape showing smoking scenes compared with non-smokers. Second, watching the videotape showing smoking scenes compared with the control videotape in still-smokers resulted in increased metabolic rates in the striatum, thalamus and midbrain. Third, the ratings of the urge to smoke cigarettes while watching the videotape showing smoking scenes in still-smokers were associated with brain metabolic activity in the ventral striatum, anterior cingulate, orbitofrontal cortex, middle temporal lobe, hippocampus, insula, midbrain and thalamus. In conclusion, successfully treated smokers showed attenuated craving and reduced activity in the mesolimbic reward circuit.

Diagnosis of intrathoracic lesions: are sequential fine-needle aspiration (FNA) and core needle biopsy (CNB) combined better than either investigation alone?

AIM: To assess the diagnostic accuracy of sequential computed tomography (CT)-guided percutaneous fine-needle aspiration (FNA) and core-needle biopsy (CNB) in comparison with FNA and CNB performed separately for diagnosing intrathoracic lesions. SUBJECTS AND METHODS: Five hundred and eighty-two consecutive patients with thoracic lesions who underwent same-session sequential CT-guided FNA and CNB procedures were studied. The final diagnosis, which was achieved by either agreement of percutaneous procedures with clinical follow-up, bronchoscopy or thoracotomy was available for all cases. The diagnostic yield of the combined FNA+CNB procedures was compared with that of each alone. RESULTS: Adequate samples were obtained in 541 (93%) of FNAs and 513 (88%) of CNBs. Of 582 lesions, 419 (72%) were malignant and 163 (28%) were benign. For malignant lesions, the sensitivity, specificity and accuracy of the procedures were: 376/419 (89.7%), 136/163 (83.4%), and 88% for FNA; 317/419 (75.6%), 138/163 (84.7%), and 78% for CNB; 400/419 (95.5%), 154/163 (94.5%), and 95% for FNA+CNB. The sequential procedures showed significantly better sensitivity, specificity and accuracy compared with either FNA or CNB separately (p<0.003). For the 163 benign lesions, 76 (47%) had a specific benign pathological diagnosis. The diagnosis was obtained in 16/76 (21%) by FNA, in 54/76 (71%) by CNB, and in 60/76 (79%) by FNA+CNB. There was no significant difference between the results of the sequential procedures and CNB alone (p>0.05). CONCLUSIONS: Sequential FNA and CNB improve the diagnostic accuracy of percutaneous CT-guided procedures in malignant lesions. There was only mild improvement, which was not statistically significant, for the diagnosis of benign specific lesions by the sequential procedures compared with the yield of CNB alone.

Transthoracic needle biopsy of lung masses: a survey of techniques.

AIM: In order to assess the range and everyday use of the various techniques for percutaneous transthoracic needle biopsy of lung masses in the USA and Canada, we surveyed thoracic radiologists in academic and community practice on their standard approach to the procedure. MATERIALS AND METHODS: The 300 questionnaires that were mailed to members of the Society of Thoracic Radiology throughout the USA and Canada contained specific questions on their approach to a transthoracic needle biopsy of a routine case of a 3cm lung mass located in the right lower lobe 1cm from the pleural surface. RESULTS: A total of 140 (47%) members responded. Of the 139 responders who performed lung biopsies, 103 (74%) were located at a teaching centre affiliated to a university or medical school, and 36 (26%) were community-based radiologists. In total 97 (70%) replied that they would perform the procedure under CT guidance, 31 (22%) under either CT or fluoroscopy guidance, and 11 (8%) only under fluoroscopy. Fine-needle aspiration was the procedure of choice for the given case by 101 (73%) responders, whereas 20 (14%) preferred doing core biopsy, and 18 (13%) chose both techniques. On-site cytology confirmation for obtaining diagnostic material was available to 101 (73%) responders. Before performing the procedure, 107 (77%) verified coagulation tests whereas 32 (23%) did not. Follow-up imaging for pneumothorax assessment was not routinely performed by 15 (11%) responders. CONCLUSION: The majority of radiologists performed percutaneous transthoracic needle biopsy of a lung mass under CT guidance, by fine-needle aspiration, using repeated pleural puncture technique, and with a cytologist on site. A significant minority did not obtain coagulation screening before the procedure, and a small minority did not routinely assess for pneumothorax by late chest radiography.

Induced sputum-retrieved matrix metalloproteinase 9 and tissue metalloproteinase inhibitor 1 in granulomatous diseases.

Matrix metalloproteinases (MMPs) capable of degrading various components of connective tissue matrices, and tissue inhibitor metalloproteinases (TIMPs) are considered important in lung parenchymal remodeling and repair processes in pulmonary diseases. Induced sputum (IS) is a reliable noninvasive method to investigate pathogenesis, pathophysiology and treatment of lung disease. This study was designed to determine whether IS-MMP9/TIMP1 levels demonstrate lung parenchymal remodeling in sarcoidosis (SA) and Crohn's disease (CRD) patients. Sputum was induced and processed conventionally in 13 SA patients, 18 CRD patients and 9 controls. Two-hundred cells were counted on Giemsa-stained cytopreps, and T lymphocytes subsets (CD4 = T helper and CD8 = T suppressor cytotoxic cells) were analysed by FACS using monoclonal antibodies.MMP-9 and TIMP-1 were measured using commercial ELISA kits. MMP-9 concentrations, but not those of TIMP-1, were significantly greater in the sputum supernatant in SA and CRD patients compared to controls (P = 0.018 and P = 0.0019, respectively). The molar ratio, MMP-9/TIMP-1, was significantly higher in SA and CRD patients compared to controls (P = 0.008 and P = 0.024, respectively). Gelatinase species having a molecular weight similar to that of MMP-9 were demonstrated by zymographic analysis. MMP-9 levels were highly correlated with the CD4/CD8 ratio and DLCO capacity in SA but less in CRD patients. MMP-9 levels in IS provide a sensitive marker for pulmonary damage.

Correlation between c-erbB-4 receptor expression and response to gemcitabine-cisplatin chemotherapy in non-small-cell lung cancer.

BACKGROUND: While the overexpression of c-erbB gene family in several malignancies is associated with poorer prognosis, the association between the expression of the cellular markers and the response to chemotherapy is not yet clear. In this study we investigated the expression of c-erbB-4 receptor in NSCLC and correlated it with the response to gemcitabine-cisplatin combination chemotherapy. PATIENTS AND METHODS: Forty-three NSCLC patients with histologically or cytologically proven disease were treated with gemcitabine-cisplatin combination chemotherapy. Immunohistochemical stains for c-erbB-4 receptor were performed in 20 cases on paraffin sections using the avidin-biotin-peroxidase method. RESULTS: Two patients achieved complete response (5%), and 16 achieved partial response (37%) yielding an overall objective response rate of 42%. Minimal response was observed in seven patients (16%) and disease stabilization in 7%. Immunohistochemical stain was positive for the presence of c-erbB-4 receptor in 25% of patients, and negative in 75%. No response was documented in c-erbB-4 positive patients (0 of 5) while an objective response (complete, partial or minimal) was seen in 11 of 15 (73%) c-erbB-4 negative patients. Negative stain for c-erbB-4 significantly favored response to gemcitabine-cisplatin combination (P < 0.01). CONCLUSION: C-erbB-4 expression status showed no correlation with survival and cannot be accepted at this time as a guiding factor for therapeutic management. These interesting results deserve further evaluation in a large-scale prospective trial before treatment recommendations on the basis of c-erbB-4 presence can be finally made.

Correlative study of preoperative transthoracic core cutting needle biopsy of focal thoracic lesions and thoracotomy findings.

We conducted a retrospective study to determine the clinical utility of percutaneous core needle biopsy (PCNBx) in 36 patients with peripheral focal chest lesions who later underwent thoracic surgery for diagnostic or therapeutic purposes. PCNBx provided adequate material in 31/36 cases, giving an overall sample yield of 86.1%. PCNBx diagnosis was confirmed by surgery in 27/31 patients, giving a sensitivity of 91.6% and a specificity of 87.5%. In 4 patients, the lesions were misdiagnosed by PCNBx. In 5 patients with benign processes, surgical intervention could have been avoided, according to PCNBx results. The rate of PCNBx-induced pneumothorax was 11%. Radiologically guided PCNBx is an easy and safe procedure that can provide important preoperative diagnostic information and can circumvent the need for exploratory diagnostic surgery in cases of benign lesions. PCNBx also allows better preoperative planning in cases of malignancy.

Severe allergic bronchopulmonary aspergillosis in an infant with cystic fibrosis and her asthmatic father.

An infant with cystic fibrosis and her asthmatic father were diagnosed as suffering from allergic bronchopulmonary aspergillosis (ABPA). Cystic fibrosis was diagnosed in the infant at 6 weeks of age, and gene mutations were W1282X/G542X. She was diagnosed definitively as suffering from ABPA at age 3.5 years, but had suggestive symptoms from age 11 months. This may be the youngest age described to date for ABPA. The child responded well to systemic steroid therapy, but remained steroid-dependent over the next 4 years. Treatment with itraconazole enabled a marked reduction in steroid dosage. The father was an asthmatic, and a heterozygote for the cystic fibrosis transmembrane regulator (CFTR) mutation W1282X. He had a normal sweat test, atopy, and moderate reversible airway obstruction. There was no proven exposure to Aspergillus in the home environment. The importance of considering the diagnosis of ABPA even in infancy, the therapeutic dilemmas, and the possible role of abnormal CFTR function in the development of ABPA are discussed.

Eosinophil influx into the airways in patients with exercise-induced asthma.

Exercise-induced asthma is a common phenomenon, the mechanism of which is undetermined. Eosinophils have been suggested as playing a role in its occurrence. We studied the effect of exercise-induced asthma on the cellular and mediator composition of spontaneously obtained sputum. Twenty-five patients with bronchial asthma were investigated by studying sputum spontaneously obtained before and following challenge. One group with (n=9) and one without (n=9) exercise-induced asthma performed exercise challenge. A third group (n=7) performed methacholine challenge. The sputum was analysed using Giemsa staining for differential cell count, measuring eosinophil cationic proteins and mixtures of leukotrienes (D4, E4 and C4) in the liquid phase using ELISA. The group with exercise-induced asthma had a mean drop of 23.7+/-7.4% in FEV1, significantly (P=0.001) higher than the group without it. Following challenges, there were significant increases in sputum eosinophils only in the group with exercise-induced asthma (from 8.1+/-13.9% to 18.3+/-20.2%, P=0.0017) and not in control groups (from 0.9+/-0.9% to 1.5+/-15%) or in those who had methacholine challenge (from 23.6+/-27.2% to 22.3+/-23.8%). Eosinophil cationic proteins did not change significantly in any group. In the liquid phase of the sputum, the amount of leukotrienes increased following exercise in six of the seven patients with exercise-induced asthma in whom it was measured. The influx of eosinophils to the airway in patients who develop exercise-induced asthma can be partially explained by the leukotrienes in the airways of those patients.

Induced sputum compared to bronchoalveolar lavage for evaluating patients with sarcoidosis and non-granulomatous interstitial lung disease.

Bronchoalveolar lavage (BAL), an important tool for evaluating interstitial lung diseases (ILDs), has limited utility due to its invasiveness and the difficulty of performing it in clinically contraindicated patients. We compared BAL with the induced sputum (IS) technique to analyse cells and T lymphocytes in patients with sarcoidosis (SA) and non-granulomatous ILD (NG-ILD). Pulmonary function tests and BAL were performed by conventional methods. IS induction was done 20 sec after inhalation of 3.5% saline with an ultrasonic nebulizer. Giemsa-stained cytopreps were differentially counted. T lymphocyte subsets were analysed by flow activated cell sorter (FACS). Patients with NG-ILD had impaired total lung capacity (TLC). Transbronchial biopsy demonstrated lung fibrosis in NG-ILD and non-caseating granuloma in SA. The differential cell count in both groups demonstrated a significantly lower percentage of neutrophils and a significantly higher percentage of macrophages in BAL than in IS. The IS samples of patients with SA were significantly richer in metachromatic cells and eosinophils, but had a lower percentage of lymphocytes, compared to the BAL samples. The profiles of T cell subsets showed the same pattern, in both samples, in both groups. A CD4/CD8 ratio of 2.5 or greater had a sensitivity of 100% and a specificity of 81.2%, with a positive predictive value of 81.2% to distinguish SA from NG-ILD. IS is an effective non-invasive technique to identify CD4+ inflammation which distinguishes sarcoidosis from other NG-ILDs.

Percutaneous core needle biopsy in the diagnosis of mediastinal tumors.

OBJECTIVE: to determine the contribution of percutaneous core cutting needle biopsy (PCNB) in the diagnosis of mediastinal tumors. DESIGN: retrospective review of 70 patients with mediastinal lesions who underwent CT-guided PCNB between 1988 and 1996. RESULTS: PCNB provided adequate material in 62/70 cases, giving a total sample rate of 88.6%. Of these 62 patients, 57 were diagnosed correctly by PCNB whereas 5/62 were misdiagnosed as nonspecific inflammation, providing an overall sensitivity of 91.9%. PCNB established a specific histologic diagnosis in 90.3% of the patients, mainly in cases of lymphoma, bronchogenic carcinoma, and thymoma. Pneumothorax was the most commonly encountered complication (11%). Hemoptysis (30-50 ml) occurred in only one (1.6%) of the patients. CONCLUSION: CT guided PCNB is an easy and safe procedure which can provide a precise diagnosis in the majority of mediastinal tumors and can obviate the need for exploratory thoracic surgery in cases which are medically treatable or non-resectable.

Percutaneous core needle biopsy vs. fine needle aspiration in diagnosing benign lung lesions.

OBJECTIVE: To determine the diagnostic value of percutaneous core needle biopsy (PCNB) in comparison with fine needle aspiration (FNA) in patients with benign pulmonary lesions. STUDY DESIGN: A retrospective review was undertaken of computed tomography-guided PCNBs and FNAs performed between 1988 and 1997. Both FNA and PCNB biopsies were carried out sequentially at the same visit in every patient. RESULTS: A specific benign diagnosis was made in 10/60 cases (16.7%) by FNA and in 49/60 (81.7%) by PCNB. PCNB findings resulted in significant modification of the diagnosis established by FNA. The only significant complication encountered was pneumothorax, at a rate of 11.7%, which is compatible with that reported in the literature for complications induced by FNA alone. CONCLUSION: Radiologically guided PCNB is a safe procedure, can provide sufficient histologic material for a specific diagnosis of peripheral lung disease and can avoid more-invasive surgical procedures in many cases. Our experience demonstrated that the histologic analysis provided by PCNB can greatly increase the diagnostic accuracy in benign pulmonary diseases as compared with the yield of FNA.

Assessment of hazardous dust exposure by BAL and induced sputum.

OBJECTIVES: BAL, an important tool in assessing occupational lung diseases, is unsuitable for screening programs, exposure evaluation, or monitoring hazardous dust because it is an invasive technique. The results of induced sputum (IS) analysis were compared with BAL and evaluated as a possible alternative. METHODS: We compared BAL with IS analysis of 5 workers exposed to asbestos and 14 exposed to silica and hard metals. Pulmonary function tests and BAL were performed by conventional methods. IS induction was performed after a 20-min inhalation of 3.5% saline solution with an ultrasonic nebulizer. Giemsa-stained cytopreparations were differentially counted. T-lymphocyte subsets were analyzed by flow-activated cell sorter, and messenger RNA (mRNA) was transcribed by reverse transcriptase-polymerase chain reaction. Mineralogic particles were analyzed by scanning electron microscopy and polarizing light microscopy and quantified by an analyzer. RESULTS: The percentage of neutrophils was significantly lower in BAL fluid than in IS specimens, whereas no differences were found in the percentage of lymphocytes and subsets profile. Asbestos fibers were found in BAL but not in IS samples from workers exposed to asbestos. Polarizing particles were found in both samples. Similar mineral elements were found in qualitative analysis by scanning electron microscopy. Quantitative studies showed similar size distribution with a small shift toward larger particles in sputum; mRNA showed the same cytokine profile. CONCLUSIONS: A comparison of BAL and IS specimens in the evaluation of the study population yielded similar quantitative and qualitative results. Further research is needed to evaluate the hypothesis that IS, being a noninvasive technique, may be useful in monitoring exposed workers.

Tattooing and body piercing. Body art practices among college students.

Tattooing and body piercing are increasing, especially among college students. A study of 766 tattooed and/or body-pierced college students in 18 universities across the United States and one in Australia was conducted to discover the demographic characteristics, motivational factors, and health concerns. The traditional college time of 18 to 22 years of age (69%) was when they obtained their tattoo (73%) and/or body piercing (63%). More frequent health problems and impulsive decision making were noted for those with body piercing when compared to those tattooed. Three cases of hepatitis were reported. Health professionals should openly discuss body art with students, convey a nonjudgmental attitude, and assist with informed decision-making information to either reduce risks or dissuade. Open communication and applicable health education will be very important.

The living canvas.

In the United States, body art has gradually moved from the fringes of society into the mainstream. This article focuses on the health issues surrounding this practice. The literature cites numerous infectious diseases and complications resulting from or linked to body art. Tattoos have been linked to skin neoplasms, piercing has been associated with hepatitis B and C risk, and branding is strongly associated with infection. Although it is a theoretical risk, no documented cases of HIV have been acquired from a tattoo or piercing. In general, tattooing, piercing and branding are unlicensed and unregulated industries. In many communities, tattoo artists and establishments are not subject to health inspections, body art practitioners are not required to be trained in anatomy, infection control or universal precautions, and the contents of tattoo dyes have never received FDA approval. Healing times for body art are variable, depending on type and location. Obtaining body art is a long-term commitment, and patients should be fully aware of this.

Pleuropulmonary metastasis from an intracranial glioblastoma.

We present an unusual case of glioblastoma with intrathoracic and liver metastasis. The clinical diagnosis was confirmed by a percutaneous core needle biopsy from a metastatic lung lesion. The pathogenetic and diagnostic aspects of the case are discussed.

Evaluation of workers exposed to dust containing hard metals and aluminum oxide.

BACKGROUND: Fourteen worker exposed to hard metals and aluminum oxide were evaluated. METHODS: Six heavily exposed workers underwent bronchoscopy and bronchoalveolar lavage, and five workers underwent transbronchial biopsy. RESULTS: Microchemical analysis of transbronchial biopsies showed a high lung burden of exogenous particles, especially metal related to their hard metals exposure. Lung tissue and cellular changes, which were associated with exposure to hard metal and aluminum oxide, corresponded well with the microanalytic test results. CONCLUSIONS: Three workers had at biopsy diffuse interstitial inflammatory changes: two of them were asymptomatic with normal chest X-ray films, and one had clinically evident disease with severe giant cell inflammation. Two other workers showed focal inflammation. The worker showing clinical disease and one asymptomatic worker with interstitial inflammatory changes had evaluated bronchoalveolar lavage fluid-eosinophilia counts. These two were father (with clinical disease) and son (asymptomatic).