Progress on BIG 1-02/IBCSG 27-02/NSABP B-37, a prospective randomized trial evaluating chemotherapy after local therapy for isolated locoregional recurrences of breast cancer

BACKGROUND: The utility of chemotherapy for women who experience a locoregional recurrence after primary treatment of early breast cancer remains an open question. An international collaborative trial is being conducted by the Breast International Group (BIG), the International Breast Cancer Study Group (IBCSG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the effectiveness of cytotoxic therapy for these patients, either alone or in addition to selective use of hormonal therapy and trastuzumab. METHODS: The trial population includes women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery, but subsequently develop an isolated local and/or regional ipsilateral invasive recurrence. Excision of all macroscopic tumor without evidence of systemic disease is required for study entry. Patients are randomized to receive chemotherapy or no chemotherapy; type of chemotherapy is not protocol-specified. Radiation, hormonal therapy, and trastuzumab are given as appropriate. The primary endpoint is disease-free survival (DFS). Quality-of-life measurements are collected at baseline, and then at 9 and 12 months. The accrual goal is 977 patients. RESULTS: This report describes the characteristics of the first 99 patients. Sites of recurrence at study entry were: breast (56%), mastectomy scar/chest wall (35%), and regional lymph nodes (9%). Two-thirds of patients have estrogen-receptor-positive recurrences. CONCLUSION: This is the only trial actively investigating the question of "adjuvant" chemotherapy in locally recurrent breast cancer. The case mix of accrual to date indicates a broad representation of this patient population.

Langerhans cell histiocytosis as differential diagnosis of a mediastinal tumor

We describe the case of a 55-year-old man who presented with parasternal swelling. The chest CT scan showed a large tumor of the chest wall infiltrating the subcutaneous tissue. To assume histologic diagnosis an open biopsy was performed. Between the myofibrils a coarse, white tumor with infiltrative growth was noted. Histopathologic examination revealed expanded atrophic skeletal muscle that was infiltrated by histiocytic cells. Numerous eosinophilic granulocytes and lymphocytes CD20 and CD3 positive could be detected and immunohistochemical staining was also positive for S-100 proteins and CD1a. Histologic findings were characteristic of Langerhans cell histiocytosis (LCH). To the best of our knowledge a LCH originating from the mediastinum in an adult as presented has not been previously described.

Unilateral hypoplastic breast in a male-to-female transsexual with Poland syndrome after gender reassignment--reconstructive considerations

Gender reassignment procedures are performed more frequently nowadays due to a multidisciplinary approach and improved techniques and selection process. Many male-to-female patients require bilateral breast augmentation as part of the transformation following the gender reassignment if they fail to develop female breast features after hormonal treatment. We report on a very rare incidence of male-to-female gender reassignment in a patient with Poland syndrome. A male-to-female transsexual on hormonal therapy for gender reassignment developed one normal female-shaped breast whereas the other breast remained hypoplastic. As a male, he was not aware of his chest wall deformity but it became a major issue after successful gender reassignment surgery. Our experience with the specific reconstructive considerations and recommendations regarding our surgical approach to this complex reconstructive problem are discussed.

Beamlet based direct aperture optimization for MERT using a photon MLC

PURPOSE A beamlet based direct aperture optimization (DAO) for modulated electron radiotherapy (MERT) using photon multileaf collimator (pMLC) shaped electron fields is developed and investigated. METHODS The Swiss Monte Carlo Plan (SMCP) allows the calculation of dose distributions for pMLC shaped electron beams. SMCP is interfaced with the Eclipse TPS (Varian Medical Systems, Palo Alto, CA) which can thus be included into the inverse treatment planning process for MERT. This process starts with the import of a CT-scan into Eclipse, the contouring of the target and the organs at risk (OARs), and the choice of the initial electron beam directions. For each electron beam, the number of apertures, their energy, and initial shape are defined. Furthermore, the DAO requires dose-volume constraints for the structures contoured. In order to carry out the DAO efficiently, the initial electron beams are divided into a grid of beamlets. For each of those, the dose distribution is precalculated using a modified electron beam model, resulting in a dose list for each beamlet and energy. Then the DAO is carried out, leading to a set of optimal apertures and corresponding weights. These optimal apertures are now converted into pMLC shaped segments and the dose calculation for each segment is performed. For these dose distributions, a weight optimization process is launched in order to minimize the differences between the dose distribution using the optimal apertures and the pMLC segments. Finally, a deliverable dose distribution for the MERT plan is obtained and loaded back into Eclipse for evaluation. For an idealized water phantom geometry, a MERT treatment plan is created and compared to the plan obtained using a previously developed forward planning strategy. Further, MERT treatment plans for three clinical situations (breast, chest wall, and parotid metastasis of a squamous cell skin carcinoma) are created using the developed inverse planning strategy. The MERT plans are compared to clinical standard treatment plans using photon beams and the differences between the optimal and the deliverable dose distributions are determined. RESULTS For the idealized water phantom geometry, the inversely optimized MERT plan is able to obtain the same PTV coverage, but with an improved OAR sparing compared to the forwardly optimized plan. Regarding the right-sided breast case, the MERT plan is able to reduce the lung volume receiving more than 30% of the prescribed dose and the mean lung dose compared to the standard plan. However, the standard plan leads to a better homogeneity within the CTV. The results for the left-sided thorax wall are similar but also the dose to the heart is reduced comparing MERT to the standard treatment plan. For the parotid case, MERT leads to lower doses for almost all OARs but to a less homogeneous dose distribution for the PTV when compared to a standard plan. For all cases, the weight optimization successfully minimized the differences between the optimal and the deliverable dose distribution. CONCLUSIONS A beamlet based DAO using multiple beam angles is implemented and successfully tested for an idealized water phantom geometry and clinical situations.

Time-varying signal analysis to detect high-altitude periodic breathing in climbers ascending to extreme altitude.

This work investigates the performance of cardiorespiratory analysis detecting periodic breathing (PB) in chest wall recordings in mountaineers climbing to extreme altitude. The breathing patterns of 34 mountaineers were monitored unobtrusively by inductance plethysmography, ECG and pulse oximetry using a portable recorder during climbs at altitudes between 4497 and 7546 m on Mt. Muztagh Ata. The minute ventilation (VE) and heart rate (HR) signals were studied, to identify visually scored PB, applying time-varying spectral, coherence and entropy analysis. In 411 climbing periods, 30-120 min in duration, high values of mean power (MP(VE)) and slope (MSlope(VE)) of the modulation frequency band of VE, accurately identified PB, with an area under the ROC curve of 88 and 89%, respectively. Prolonged stay at altitude was associated with an increase in PB. During PB episodes, higher peak power of ventilatory (MP(VE)) and cardiac (MP(LF)(HR) ) oscillations and cardiorespiratory coherence (MP(LF)(Coher)), but reduced ventilation entropy (SampEn(VE)), was observed. Therefore, the characterization of cardiorespiratory dynamics by the analysis of VE and HR signals accurately identifies PB and effects of altitude acclimatization, providing promising tools for investigating physiologic effects of environmental exposures and diseases.

Single photon emission mammography with convergent collimators

Tese de doutoramento, Engenharia Biomédica e Biofísica, Universidade de Lisboa, Faculdade de Ciências, 2016

Extensive En block resection and adjunctive chemotherapy of a canine primary rib osteosarcoma

The management of a large rib osteosarcoma in a two-year-old neutered male Golden Retriever is reported. The tumour was initially misdiagnosed as a chondrosarcoma following incisional biopsy. Extensive en bloc resection and chest wall reconstruction with propylene mesh was performed, and carboplatin was administered postoperatively. Approximately 270 days after surgery there was no evidence of tumour recurrence and the patient was disease free.

The effect of caudal block on functional residual capacity and ventilation homogeneity in healthy children

Caudal block results in a motor blockade that can reduce abdominal wall tension. This could interact with the balance between chest wall and lung recoil pressure and tension of the diaphragm, which determines the static resting volume of the lung. On this rationale, we hypothesised that caudal block causes an increase in functional residual capacity and ventilation distribution in anaesthetised children. Fifty-two healthy children (15-30 kg, 3-8 years of age) undergoing elective surgery with general anaesthesia and caudal block were studied and randomly allocated to two groups: caudal block or control. Following induction of anaesthesia, the first measurement was obtained in the supine position (baseline). All children were then turned to the left lateral position and patients in the caudal block group received a caudal block with bupivacaine. No intervention took place in the control group. After 15 nun in the supine position, the second assessment was performed. Functional residual capacity and parameters of ventilation distribution were calculated by a blinded reviewer. Functional residual capacity was similar at baseline in both groups. In the caudal block group, the capacity increased significantly (p < 0.0001) following caudal block, while in the control group, it remained unchanged. In both groups, parameters of ventilation distribution were consistent with the changes in functional residual capacity. Caudal block resulted in a significant increase in functional residual capacity and improvement in ventilation homogeneity in comparison with the control group. This indicates that caudal block might have a beneficial effect on gas exchange in anaesthetised, spontaneously breathing preschool-aged children with healthy lungs.

Evaluation of the Does Reduction Potential Using a Breast Positioning Technique for Organ-based Tube Current Modulated CT Examinations

Purpose: The purpose of this work was to investigate the breast dose saving potential of a breast positioning technique (BP) for thoracic CT examinations with organ-based tube current modulation (OTCM).

Methods: The study included 13 female patient models (XCAT, age range: 27-65 y.o., weight range: 52 to 105.8 kg). Each model was modified to simulate three breast sizes in standard supine geometry. The modeled breasts were further deformed, emulating a BP that would constrain the breasts within 120° anterior tube current (mA) reduction zone. The tube current value of the CT examination was modeled using an attenuation-based program, which reduces the radiation dose to 20% in the anterior region with a corresponding increase to the posterior region. A validated Monte Carlo program was used to estimate organ doses with a typical clinical system (SOMATOM Definition Flash, Siemens Healthcare). The simulated organ doses and organ doses normalized by CTDIvol were compared between attenuation-based tube current modulation (ATCM), OTCM, and OTCM with BP (OTCMBP).

Results: On average, compared to ATCM, OTCM reduced the breast dose by 19.3±4.5%, whereas OTCMBP reduced breast dose by 36.6±6.9% (an additional 21.3±7.3%). The dose saving of OTCMBP was more significant for larger breasts (on average 32, 38, and 44% reduction for 0.5, 1.5, and 2.5 kg breasts, respectively). Compared to ATCM, OTCMBP also reduced thymus and heart dose by 12.1 ± 6.3% and 13.1 ± 5.4%, respectively.

Conclusions: In thoracic CT examinations, OTCM with a breast positioning technique can markedly reduce unnecessary exposure to the radiosensitive organs in the anterior chest wall, specifically breast tissue. The breast dose reduction is more notable for women with larger breasts.

Sternal wound dehiscence from intense coughing in a cardiac surgery patient: could it be prevented?

This case report is on a obese patient who underwent a coronary artery bypass. The immediate postoperative phase, on the 8th day, was characterized by sternal dehiscence with diastasis, from intense coughing. At present, for obese patients there are not any guidelines aimed to prevent the sternal diastasis. The use of a sternum support vest after median sternotomy could be a valuable tool in the postoperative care of our patients, in order to avoid chest wall hyperexpansion and to prevent sternal wound dehiscence and diastasis.

Three-dimensional, in-silico breast phantom for multimodality image simulations

We report on the construction of anatomically realistic three-dimensional in-silico breast phantoms with adjustable sizes, shapes and morphologic features. The concept of multiscale spatial resolution is implemented for generating breast tissue images from multiple modalities. Breast epidermal boundary and subcutaneous fat layer is generated by fitting an ellipsoid and 2nd degree polynomials to reconstructive surgical data and ultrasound imaging data. Intraglandular fat is simulated by randomly distributing and orienting adipose ellipsoids within a fibrous region immediately within the dermal layer. Cooper’s ligaments are simulated as fibrous ellipsoidal shells distributed within the subcutaneous fat layer. Individual ductal lobes are simulated following a random binary tree model which is generated based upon probabilistic branching conditions described by ramification matrices, as originally proposed by Bakic et al [3, 4]. The complete ductal structure of the breast is simulated from multiple lobes that extend from the base of the nipple and branch towards the chest wall. As lobe branching progresses, branches are reduced in height and radius and terminal branches are capped with spherical lobular clusters. Biophysical parameters are mapped onto the complete anatomical model and synthetic multimodal images (Mammography, Ultrasound, CT) are generated for phantoms of different adipose percentages (40%, 50%, 60%, and 70%) and are analytically compared with clinical examples. Results demonstrate that the in-silico breast phantom has applications in imaging performance evaluation and, specifically, great utility for solving image registration issues in multimodality imaging.

Chest pain and ST-segment elevation in a patient with Duchenne muscular dystrophy, what really happened?

Introduction: Myocardial infarction is rare in children, if it occurs, findings are almost similar to adults. In Ouchenne muscular dystrophy (OMO), ST segment displacement associated with typical chest pain can occur. We report the case of a young boy with OMO presenting symptoms suggestive of myocardial ischemia. Case report: 7 year old boy, diagnosed with OMO, eoming to the emergency department with complaints of acute chest pain, dyspnoea and anxiety the night before. Clinical examination was not remarkable, with exception of findings of the OMO. ECG showed important ST-segment elevation in right precordial leads. Major increase in troponin 1 42.33 mcg/(normal, <0.04 mcg/I) was found. Echocardiography revealed slight yskinesia of postero-septal wall without decrease in ventricular function. As acute pain had happened more han 12 hours before referral and as the child was asymptomatic, he received anti-platelets therapy. The serum level of troponin 1 declined and the ECG normalised in a few days. Cardiac catheterization did not show any coronary anomaly or eardiac dysfunction. Cardiac biopsy revealed myocardial cell damaged compatible with OMO cardiomyopathy. Tc99m myocardial single-photon emission computed tomography (SPECT) did not show any radionuclide uptake defect. Conclusions: ln this particular context of children with OMO, the classical signs of myocardial ischemia could be misleading, standard investigation failed to demonstrate the cause of chest pain and inerease of troponin l, there was also no evidence of myocarditis. Role of late enhancement (LE) signal in eontrast-enhanced MRI in the understanding of the occurring process has to be evaluated.

Endovascular treatment of aortic rupture by blunt chest trauma.

BACKGROUND: The usual treatment of blunt aortic injury (BAI) is prompt surgery. Frequently severe injuries to the brain or lungs exclude further surgical treatment. The purpose of this study is to assess the feasibility of placing endovascular stent-grafts. METHODS: From 1992 through 1999, in our primary and referral trauma center, 26 acute BAI, 21 males and 5 females, mean age 40.2+/-16.3 yrs were diagnosed. The last 4 patients underwent prospectively endovascular repair with Talent endograft. Endoprosthesis parameters were measured on three-dimensional spiral CT reconstruction. While waiting for devices, blood pressure was aggressively lowered and aortic lesions were monitored by transesophageal echography. RESULTS: Stent-graft deployment was successful in all 4 patients. There were no complications of endoleak, stent migration, paraplegia or death. Angiographic exclusion was complete in all 4 patients. CT scans at a mean follow-up of 11+/-5 months showed complete healing of the aortic wall in all patients. CONCLUSIONS: For stable acute BAI, endovascular stent-graft repair is feasible and safe, and is an effective therapeutic alternative to open surgery. Because of the normal proximal and distal wall in aortic injuries, endoluminal treatment might be the therapy of choice in the near future.

Right ventricular rupture due to recurrent mediastinal infection with a closed chest.

Right ventricular (RV) rupture in cases of mediastinitis following cardiac surgery is a rare and dangerous complication. Bleeding from the right ventricle occurs mainly after sternal reopening, due to either iatrogenic manipulation (wire removal, lesions due to wiring maneuvers) or mechanical shearing forces, producing direct injury. We present a case of RV wall perforation due to infection in a recurrent postoperative mediastinitis with a closed chest. The current literature on treatment of postoperative mediastinitis is also reviewed.

Teaching project: a low-cost swine model for chest tube insertion training

Objective: to describe and evaluate the acceptance of a low-cost chest tube insertion porcine model in a medical education project in the southwest of Paraná, Brazil. Methods: we developed a low-cost and low technology porcine model for teaching chest tube insertion and used it in a teaching project. Medical trainees - students and residents - received theoretical instructions about the procedure and performed thoracic drainage in this porcine model. After performing the procedure, the participants filled a feedback questionnaire about the proposed experimental model. This study presents the model and analyzes the questionnaire responses. Results: seventy-nine medical trainees used and evaluated the model. The anatomical correlation between the porcine model and human anatomy was considered high and averaged 8.1±1.0 among trainees. All study participants approved the low-cost porcine model for chest tube insertion. Conclusion: the presented low-cost porcine model for chest tube insertion training was feasible and had good acceptability among trainees. This model has potential use as a teaching tool in medical education.