Target therapy in elderly breast cancer patients.

Substantial progress has been made in the management of breast cancer by targeting HER2 and VEGF pathways. Although the efficacy and safety of target therapy in breast cancer have been established, no specific phase III trial has addressed these issues in the elderly population and the only data available derive from subanalyses or retrospective series. The aim of this review is to summarize the available evidence in this special population and to encourage further well designed studies in elderly breast cancer patients.

Intramural ganglion structures in esophageal atresia: a morphologic and immunohistochemical study.

Introduction and Aim. Disorders of esophageal motility causing dysphagia and gastroesophageal reflux are frequent in survivors to esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). The aim of the present study was to investigate the histologic and immunohistochemical features in both esophageal atretic segments to further understand the nature of the motor disorders observed in these patients. Material and Methods. Esophageal specimens from 12 newborns with EA/TEF and 5 newborns dead of unrelated causes were examined. The specimens were fixed in 5% buffered formalin, included in paraffin and cut in 5 micron sections that were stained with hematoxilin and eosin (H and E), and immunohistochemical stainings for Actin, S-100 protein, Neurofilament, Neuron-Specific-Enolase, Chromogranin A and Peripherin were evaluated under the microscope. Results. In controls, the distribution of the neural elements was rather homogenous at both levels of the esophagus. In contrast, the atretic segments showed quantitative and qualitative differences between them with sparser nervous tissue in the distal one in comparison with the proximal one and with controls. Conclusions. These results further support the assumption that histomorphological alterations of the muscular and nervous elements within the esophageal wall might contribute to esophageal dysmotility in patients surviving neonatal operations for EA/TEF.

The Modified Kimura's Technique for the Treatment of Duodenal Atresia.

Background/Purpose. Kimura's diamond-shaped-duodenoduodenostomy (DSD) is a known technique for the correction of congenital intrinsic duodenal obstruction. We present a modification of the technique and review the advantages of this new technique. Methods. From 1992 to 2006, 14 newborns were treated for duodenal atresia. We inverted the direction of the duodenal incisions: a longitudinal incision was made in the proximal duodenum while the distal was opened by transverse incision. Results. Our "inverted-diamond-shaped-duodenoduodenostomy" (i-DSD) allowed postoperative oral feeding to start on days 2 to 3, peripheral intravenous fluids discontinuity on days 3 to 8 (median values 3.6); time to achieve full oral feeds on days 8 to 12 (median values 9.4); the length of hospitalisation ranged from 10 and 14 days (median value 11.2). No complications related to the anastomosis, by Viz leakage, dehiscence, biliary stasis, or stenosis were observed. Conclusions. The i-DSD provides a safe procedure to protect the ampulla of Vater from injury and avoids any formation of a blind loop. The results show that patients who have i-DSD achieve full oral feeds in a very short time period and, consequently, the length of hospitalisation is also significantly reduced.

Transcranial Doppler ultrasonography in the assessment of cerebral circulation arrest: improving sensitivity by transcervical and transorbital carotid insonation and serial examinations.

INTRODUCTION: Transcranial Doppler (TCD) can detect the cerebral circulation arrest (CCA) in brain death. TCD is highly specific, but less sensitive because of false-negatives accounting for up to 10%. The aim of the study was to explore the diagnostic accuracy of TCD and to determine whether it can be augmented by strategies such as the insonation of the extracranial internal carotid artery (ICA) and sequential examinations. METHODS: Data of 184 patients, who met clinical criteria of brain death, observed from 1998 through 2006, were retrospectively reviewed. The study of cerebral arteries was performed through the transtemporal approach, suboccipital insonation of the vertebro-basilar system, transorbital insonation of the ICA and ophthalmic artery, and transcervical insonation of the extracranial ICA. Repeated exams were performed in cases of persistent diastolic flow. RESULTS: The specificity of the testing was 100%, no false-positive cases were recorded. The sensitivity of conventional TCD examination was 82.1%. The insonation of the extracranial ICA increased sensitivity to 88% allowing the detection of CCA in those patients lacking temporal windows; serial examinations further increased sensitivity to 95.6%. CONCLUSIONS: The addition of insonation of the cervical ICA and of the siphon increased sensitivity of TCD. Nevertheless, a CCA flow patterns may appear later on those segments. Serial examinations, may be needed in those cases.

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer.

BACKGROUND: A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2. PATIENTS AND METHODS: Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m2) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD). RESULTS: Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035). CONCLUSION: Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+.

Hypercapnia: what is the limit in paediatric patients? A case of near-fatal asthma successfully treated by multipharmacological approach.

We describe a case of prolonged severe hypercapnia with respiratory acidosis occurring during an episode of near-fatal asthma in an 8-year-old boy, followed by complete recovery. After admission to the intensive care unit, despite treatment with maximal conventional bronchodilatative therapy, the clinical picture deteriorated with evident signs of respiratory muscle fatigue. The child was sedated, intubated and mechanically ventilated. Magnesium sulphate, ketamine and sevoflurane were gradually introduced together with deep sedation, curarization and continuous bronchodilatative therapy. Ten hours after admission, arterial pCO2 reached 39 kPa (293 mmHg), pH was 6.77 and pO2 8.6 kPa (65 mmHg). Chest radiograph showed severe neck subcutaneous emphysema, with signs of mediastinal emphysema. No episode of haemodynamic instability was seen despite severe prolonged hypercapnia lasting more than 14 h. Oxygenation was maintained and successful recovery followed without neurological or cardiovascular sequelae. This case shows the cardiovascular and neurological tolerance of a prolonged period of supercarbia in a paediatric patient. The most important lesson to be learned is the extreme importance of maintaining adequate tissue perfusion and oxygenation during an asthma attack. The second lesson is that when conventional bronchodilators fail, the intensivist may resort to the use of drugs such as ketamine, magnesium sulphate and inhalation anaesthesia. In this context deep sedation and curarization are important not only to improve oxygenation, but also to reduce cerebral metabolic requirements.