Correction of pectus excavatum combined with open heart surgery in a patient with Marfan's syndrome.

We report a patient with Marfan's syndrome and pectus excavatum who underwent open heart surgery with simultaneous correction of the sternal malformation. Permanent internal stabilization, achieved by bilateral overlapping of the bevelled ends of the lowest ribs and reinforced with sternal closure wires offered a maintained postoperative chest wall stability, avoided the potential postoperative complications of cardiac compression, and improved the aesthetic appearance of the anterior chest wall. The increased risk of bleeding due to extensive dissection was minimized by postponing the repair of pectus excavatum to when protamin is administered after termination of cardiopulmonary bypass.

A novel technique using echocardiography to evaluate venous cannula performance perioperatively in CPB cardiac surgery.

OBJECTIVE: Transthoracic echocardiography (TTE) has been used clinically to disobstruct venous drainage cannula and to optimise placement of venous cannulae in the vena cava but it has never been used to evaluate performance capabilities. Also, little progress has been made in venous cannula design in order to optimise venous return to the heart lung machine. We designed a self-expandable Smartcanula (SC) and analysed its performance capability using echocardiography. METHODS: An epicardial echocardiography probe was placed over the SC or control cannula (CTRL) and a Doppler image was obtained. Mean (V(m)) and maximum (V(max)) velocities, flow and diameter were obtained. Also, pressure drop (DeltaP(CPB)) was obtained between the central venous pressure and inlet to venous reservoir. LDH and Free Hb were also compared in 30 patients. Comparison was made between the two groups using the student's t-test with statistical significance established when p<0.05. RESULTS: Age for the SC and CC groups were 61.6+/-17.6 years and 64.6+/-13.1 years, respectively. Weight was 70.3+/-11.6 kg and 72.8+/-14.4 kg, respectively. BSA was 1.80+/-0.2 m(2) and 1.82+/-0.2 m(2), respectively. CPB times were 114+/-53 min and 108+/-44 min, respectively. Cross-clamp time was 59+/-15 min and 76+/-29 min, respectively (p=NS). Free-Hb was 568+/-142 U/l versus 549+/-271 U/l post-CPB for the SC and CC, respectively (p=NS). LDH was 335+/-73 mg/l versus 354+/-116 mg/l for the SC and CC, respectively (p=NS). V(m) was 89+/-10 cm/s (SC) versus 63+/-3 cm/s (CC), V(max) was 139+/-23 cm/s (SC) versus 93+/-11 cm/s (CC) (both p<0.01). DeltaP(CPB) was 30+/-10 mmHg (SC) versus 43+/-13 mmHg (CC) (p<0.05). A Bland-Altman test showed good agreement between the two devices used concerning flow rate calculations between CPB and TTE (bias 300 ml+/-700 ml standard deviation). CONCLUSIONS: This novel Smartcanula design, due to its self-expanding principle, provides superior flow characteristics compared to classic two stage venous cannula used for adult CPB surgery. No detrimental effects were observed concerning blood damage. Echocardiography was effective in analysing venous cannula performance and velocity patterns.

Delayed referral and gram-negative organisms increase the conversion thoracotomy rate in patients undergoing video-assisted thoracoscopic surgery for empyema

BACKGROUND: The role of video-assisted thoracoscopic surgery in the treatment of pleural empyema was assessed in a consecutive series of 328 patients between 1992 and 2002. An analysis of the predicting factors for conversion thoracotomy in presumed stage II empyema was performed. METHODS: Empyema stage III with pleural thickening and signs of restriction on computer tomography imaging was treated by open decortication, whereas a thoracoscopic debridement was attempted in presumed stage II disease. Conversion thoracotomy was liberally used during thoracoscopy if stage III disease was found at surgery. Predictive factors for conversion thoracotomy were calculated in a multivariate analysis among several variables such as age, sex, time interval between onset of symptoms and surgery, involved microorganisms, and underlying cause of empyema. RESULTS: Of the 328 patients surgically treated for stage II and III empyema, 150 underwent primary open decortication for presumed stage III disease. One hundred seventy-eight patients with presumed stage II empyema underwent a video-assisted thoracoscopic approach. Of these 178 patients, thoracoscopic debridement was successful in 99 of 178 patients (56%), and conversion thoracotomy and open decortication was judged necessary in 79 of 178 patients (44%). The conversion thoracotomy rate was higher in parapneumonic empyema (55%) as compared with posttraumatic (32%) or postoperative (29%) empyema; however, delayed referral (p < 0.0001) and gram-negative microorganisms (p < 0.01) were the only significant predictors for conversion thoracotomy in a multivariate analysis. CONCLUSIONS: Video-assisted thoracoscopic debridement offers an elegant, minimally invasive approach in a number of patients with presumed stage II empyema. However, to achieve a high success rate with the video-assisted thoracoscopic approach, early referral of the patients to surgery is required. Conversion thoracotomy should be liberally used in case of chronicity, especially after delayed referral (> 2 weeks) and in the presence of gram-negative organisms.

Identification of molecular apocrine breast tumours by microarray analysis.

Previous microarray studies on breast cancer identified multiple tumour classes, of which the most prominent, named luminal and basal, differ in expression of the oestrogen receptor alpha gene (ER). We report here the identification of a group of breast tumours with increased androgen signalling and a 'molecular apocrine' gene expression profile. Tumour samples from 49 patients with large operable or locally advanced breast cancers were tested on Affymetrix U133A gene expression microarrays. Principal components analysis and hierarchical clustering split the tumours into three groups: basal, luminal and a group we call molecular apocrine. All of the molecular apocrine tumours have strong apocrine features on histological examination (P=0.0002). The molecular apocrine group is androgen receptor (AR) positive and contains all of the ER-negative tumours outside the basal group. Kolmogorov-Smirnov testing indicates that oestrogen signalling is most active in the luminal group, and androgen signalling is most active in the molecular apocrine group. ERBB2 amplification is commoner in the molecular apocrine than the other groups. Genes that best split the three groups were identified by Wilcoxon test. Correlation of the average expression profile of these genes in our data with the expression profile of individual tumours in four published breast cancer studies suggest that molecular apocrine tumours represent 8-14% of tumours in these studies. Our data show that it is possible with microarray data to divide mammary tumour cells into three groups based on steroid receptor activity: luminal (ER+ AR+), basal (ER- AR-) and molecular apocrine (ER- AR+).

Investigations of a thermosensitive gel to temporarily occlude crural arteries in femoro-distal bypass surgery

L'artériopathie oblitérante des membres inférieurs (AOMI) est une pathologie de plus en plus fréquemment rencontrée en raison du vieillissement le la population et de l'augmentation de la prévalence du diabète. Les patients souffrant d'AOMI se manifestant par une ichémie critique du membre nécessitent un geste de revascularisation, afin que le risque d'amputation, acte fortement morbide, soit diminué. La revascularisation par voie endovasculaire est de nos jours la technique de premier choix mais en cas d'occlusion longue des artères jambières, une approche chirurgicale avec confection d'un pontage ne peut être évitée. La technique nécessite alors, lors de la confection de l'anastomose, de l'occlusion temporaire de l'artère en amont et en aval de rartériotomie, ce qui est réalisé traditionnellement à l'aide de clamps ou cathéters intravasculaires. Ces instruments présentent différents inconvénients reconnus - efficacité médiocre au vu d'artères fortement calcifiées et induction de lésions endothéliales notamment. Un nouveau type d'instrument est apparu sur le marché après approbation de la FDA, sous forme d'un gel thermosensible qui constitue un bouchon occlusif une fois injecté dans l'artère et se dissout spontanément après quelques minutes. Ce gel ayant été expérimenté avec succès en chirurgie cardiovasculaire chez des animaux, nous avons voulu évaluer l'efficacité et l'innocuité de son utilisation lors de la réalisation de pontages fémoro-jambier dans une cohorte de vingt patients. Différents paramètres opératoires ont été notés tels que le volume de gel injecté, les temps d'occlusion efficace et de confection d'anastomose ainsi que la qualité de l'occlusion vasculaire obtenue. Une artériographie per-opératoire a été réalisée de manière systématique à la recherche d'emboles de gel résiduel. Les taux de perméabilité primaire, de sauvetage de membre et de survie à 6 mois ont été rapportés. Les résultats sont satisfaisants puisque la qualité d'occlusion a été jugée bonne à excellente dans la totalité des cas sans qu'aucun instrument d'occlusion supplémentaire n'ait dû être employé et que le temps d'occlusion dépassait légèrement le temps nécessaire à la confection de l'anastomose. L'artériographie des deux premiers cas seulement a révélé la présence d'emboles distaux, avant que nous corrigions notre technique pour obtenir une dissolution instantanée du gel. Nous avons obtenu à 6 mois un taux de perméabilité primaire de 75% avec un taux de sauvetage de membre à 87.5%, le taux de mortalité à 30 jours étant de 10% - sans relation avec le gel. En conclusion, nous avons montré que l'utilisation de ce gel comme instrument d'occlusion vasculaire temporaire est sûre et efficace lors de la chirurgie de pontage fémoro-jambier. L'hypothèse qu'il pourrait être moins délétère pour l'endothélium et contribuer ainsi à une amélioration du taux de perméabilité des pontages distaux mériterait d'être testée dans le cadre d'une étude randomisée multicentrique.

Neonatal Minimally Invasive Surgery for Congenital Diaphragmatic Hernias: a multicenter study using thoracoscopy or laparoscopy.

BACKGROUND: Minimally invasive surgery (MIS) for late-presenting congenital diaphragmatic hernia (CDH) has been described previously, but few neonatal cases of CDH have been reported. This study aimed to report the multicenter experience of these rare cases and to compare the laparoscopic and thoracoscopic approaches. METHODS: Using MIS procedures, 30 patients (16 boys and 14 girls) from nine centers underwent surgery for CDH within the first month of life, 26 before day 5. Only one patient had associated malformations. There were 10 preterm patients (32-36 weeks of gestational age). Their weight at birth ranged from 1,800 to 3,800 g, with three patients weighing less than 2,600 g. Of the 30 patients, 18 were intubated at birth. RESULTS: The MIS procedures were performed in 18 cases by a thoracoscopic approach and in 12 cases by a laparoscopic approach. No severe complication was observed. For 20 patients, reduction of the intrathoracic contents was achieved easily with 15 thoracoscopies and 5 laparoscopies. In six cases, the reduction was difficult, proving to be impossible for the four remaining patients: one treated with thoracoscopy and three with laparoscopy. The reasons for the inability to reduce the thoracic contents were difficulty of liver mobilization (1 left CDH and 2 right CDH) and the presence of a dilated stomach in the thorax. Reductions were easier for cases of wide diaphragmatic defects using thoracoscopy. There were 10 conversions (5 laparoscopies and 5 thoracoscopies). The reported reasons for conversion were inability to reduce (n = 4), need for a patch (n = 5), lack of adequate vision (n = 4), narrow working space (n = 1), associated bowel malrotation (n = 1), and an anesthetic problem (n = 1). Five defects were too large for direct closure and had to be closed with a patch. Four required conversion, with one performed through video-assisted thoracic surgery. The recurrences were detected after two primer thoracoscopic closures, one of which was managed by successful reoperation using thoracoscopy. CONCLUSIONS: In the neonatal period, CDH can be safely closed using MIS procedures. The overall success rate in this study was 67%. The indication for MIS is not related to weeks of gestational age, to weight at birth (if >2,600 g), or to the extent of the immediate neonatal care. Patients with no associated anomaly who are hemodynamically stabilized can benefit from MIS procedures. Reduction of the herniated organs is easier using thoracoscopy. Right CDH, liver lobe herniation, and the need for a patch closure are the most frequent reasons for conversion.

Sustained release of nanosized complexes of polyethylenimine and anti-TGF-beta 2 oligonucleotide improves the outcome of glaucoma surgery.

The purpose of this study was to design microspheres combining sustained delivery and enhanced intracellular penetration for ocular administration of antisense oligonucleotides. Nanosized complexes of antisense TGF-beta2 phosphorothioate oligonucleotides (PS-ODN) with polyethylenimine (PEI), and naked PS-ODN were encapsulated into poly(lactide-co-glycolide) microspheres prepared by the double-emulsion solvent evaporation method. The PS-ODN was introduced either naked or complexed in the inner aqueous phase of the first emulsion. We observed a marked influence of microsphere composition on porosity, size distribution and PS-ODN encapsulation efficiency. Mainly, the presence of PEI induced the formation of large pores observed onto microsphere surface. Introduction of NaCl in the outer aqueous phase increased the encapsulation efficiency and reduced microsphere porosity. In vitro release kinetic of PS-ODN was also investigated. Clearly, the higher the porosity, the faster was the release and the higher was the burst effect. Using an analytical solution of Fick's second law of diffusion, it was shown that the early phase of PS-ODN and PS-ODN-PEI complex release was primarily controlled by pure diffusion, irrespectively of the type of microsphere. Finally, microspheres containing antisense TGF-beta2 nanosized complexes were shown, after subconjunctival administration to rabbit, to significantly increase intracellular penetration of ODN in conjunctival cells and subsequently to improve bleb survival in a rabbit experimental model of filtering surgery. These results open up interesting prospective for the local controlled delivery of genetic material into the eye.

Tip anchor flap in decubital surgery.

Anchoring a flap remains a key procedure in decubital surgery because a flap needs to be stable against shearing forces. This allows an early mobilization and undisturbed primary wound healing. This study evaluated a uniform group of eight paraplegic patients with sacral decubital ulcers and covered the lesions using gluteal rotation flaps with a deepithelialized tip to anchor the flap subcutaneously on the contralateral ischial tuber. Initial wound healing and recurrence after one year were evaluated. All but one flap showed uneventful wound healing, and all the flaps presented without any signs of recurrence or instability. The authors suggest that sufficient anchoring using a deepithelialized part of the flap helps to integrate and stabilize sacral rotation flaps.

HER2 shedding and serum HER2 extracellular domain: Biology and clinical utility in breast cancer.

The transmembrane protein HER2 is over-expressed in approximately 15% of invasive breast cancers as a result of HER2 gene amplification. HER2 proteolytic cleavage (HER2 shedding) generates soluble truncated HER2 molecules that include only the extracellular domain and the concentration of which can be measured in the serum fraction of blood. HER2 shedding also generates a constitutively active truncated intracellular receptor of 95kDa (p95(HER2)). Another soluble truncated HER2 protein (Herstatin), which can also be found in serum, is the product of an alternatively spliced HER2 transcript. Recent preclinical findings may provide crucial insights into the biological and clinical relevance of increased sHER2 concentrations for the outcome of HER2-positive breast cancer and sensitivity to trastuzumab and lapatinib treatment. We present here the most recent findings about the role and biology of sHER2 based on data obtained using a standardized test, which has been cleared by FDA in 2000, for measuring sHER2. This test includes quality control assessments and has been already widely used to evaluate the clinical utility of sHER2 as a biomarker in breast cancer. We will describe in detail data concerning the assessment of sHER2 as a surrogate maker to optimize the evaluation of the HER2 status of a primary tumor and as a prognosis and predictive marker of response to therapies, both in early and metastatic breast cancer.

Delay of extubation in neonates and children after cardiac surgery: impact of ventilator-associated pneumonia.

OBJECTIVE: This study was undertaken to determine the delay of extubation attributable to ventilator-associated pneumonia (VAP) in comparison to other complications and complexity of surgery after repair of congenital heart lesions in neonates and children. METHODS: Cohort study in a pediatric intensive care unit of a tertiary referral center. All patients who had cardiac operations during a 22-month period and who survived surgery were eligible (n = 272, median age 1.3 years). Primary outcome was time to successful extubation. Primary variable of interest was VAP Surgical procedures were classified according to complexity. Cox proportional hazards models were calculated to adjust for confounding. Potential confounders comprised other known risk factors for delayed extubation. RESULTS: Median time to extubation was 3 days. VAP occurred in 26 patients (9.6%). The rate of VAP was not associated with complexity of surgery (P = 0.22), or cardiopulmonary bypass (P = 0.23). The adjusted analysis revealed as further factors associated with delayed extubation: other respiratory complications (n = 28, chylothorax, airway stenosis, diaphragm paresis), prolonged inotropic support (n = 48, 17.6%), and the need for secondary surgery (n = 51, 18.8%; e.g., re-operation, secondary closure of thorax). Older age promoted early extubation. The median delay of extubation attributable to VAP was 3.7 days (hazards ratio HR = 0.29, 95% CI 0.18-0.49), exceeding the effect size of secondary surgery (HR = 0.48) and other respiratory complications (HR = 0.50). CONCLUSION: VAP accounts for a major delay of extubation in pediatric cardiac surgery.

Invasive lobular breast cancer and its variants: How special are they for systemic therapy decisions?

The WHO classification of breast tumors distinguishes, besides invasive breast cancer 'of no special type' (former invasive ductal carcinoma, representing 60-70% of all breast cancers), 30 special types, of which invasive lobular carcinoma (ILC) is the most common (5-15%). We review the literature on (i) the specificity and heterogeneity of ILC biology as documented by various analytical techniques, including the results of molecular testing for risk of recurrence; (ii) the impact of lobular histology on prediction of prognosis and effect of systemic therapies in patients. Though it is generally admitted that ILC has a better prognosis than IDC, is endocrine responsive, and responds poorly to chemotherapy, currently available data do not unanimously support these assumptions. This review demonstrates some lack of specific data and a need for improving clinical research design to allow oncologists to make informed systemic therapy decisions in patients with ILC. Importantly, future studies should compare various endpoints in ILC breast cancer patients among the group of hormonosensitive breast cancer.

Postoperative subconjunctival mitomycin-C injection after non-penetrating glaucoma surgery.

PURPOSE: To evaluate subconjunctival mitomycin C (MMC) injection efficacy and safety in patients with failing glaucoma non-penetrating filtering blebs. METHODS: Twenty-eight eyes were consecutively recruited for this study. Only one eye for each patient was randomly selected. All the recruited patients had glaucoma and uncontrolled intraocular pressure after a non-penetrating filtering glaucoma surgery and/or a pathological aspect of the filtering bleb (i.e., vascularized and/or encysted). One or more MMC injections were performed under the conjunctiva closed to the bleb to improve filtration. Local effects and complications of subconjunctival MMC injections were analyzed. RESULTS: Out of the 28 patients, 21 (75%) had MMC also applied intraoperatively. The mean postoperative IOP before MMC injections was 17 +/- 6.6 mmHg. The final IOP after MMC injections was 13.9 +/- 2.9 mmHg after a mean follow-up of 6 months. A total of 67 subconjunctival MMC injections were performed with a mean of 2.9 (ranging from 1 to 5) injections per patient. The only complication found to be possibly related to MMC injections was two cases of corneal Dellen. CONCLUSION: From these preliminary results, subconjunctival MMC injections in selected cases appear to be not only safe but also effective in promoting further the postoperative IOP drop.