Abstract Adjuvant trastuzumab (AT) dramatically improved HER2-positive breast cancer prognosis. Relapsed disease after AT has different patterns and information is available from observational ...studies. In this Review Chemotherapy regimens combined to anti-HER2 blockade are discussed, focusing in particular the role of anthracyclines, taxanes and capecitabine. The use of trastuzumab beyond progression and the role of other anti-HER2 agents like lapatinib, pertuzumab and T-DM1 are explored, as also dual blockade and in trastuzumab resistant Patients. Metastatic “de novo” HER2 Luminal (co-expression of HER2 and hormone receptors) Patients are eligible for anastrozole and trastuzumab but if pretreated with trastuzumab they are also eligible for lapatinib and letrozole. In any case endocrine treatment plays a complementary role to chemotherapy which remains pivotal. The last topic explored is treatment options for patients with brain metastases where both trastuzumab given concurrent with radiotherapy or lapatinib and capecitabine appear as potentially active.
Background: One‐lung ventilation (OLV) affects respiratory mechanics and ventilation/perfusion matching, reducing functional residual capacity of the ventilated lung. While the application of a ...lung‐recruiting manoeuvre (RM) on the ventilated lung has been shown to improve oxygenation, data regarding the impact of RM on respiratory mechanics are not available.
Methods: Thirteen patients undergoing lung resection in lateral decubitus were studied. During OLV, a lung‐recruiting strategy consisting in a RM lasting 1 min followed by the application of positive end‐expiratory pressure 5 cmH2O was applied to the ventilated lung. Haemodynamics, gas exchange and respiratory mechanics parameters were recorded on two‐lung ventilation (TLVbaseline), OLV before and 20 min after the RM (OLVpre‐RM, OLVpost‐RM, respectively) and TLVend. Haemodynamics parameters were also recorded during the RM.
Results: The PaO2/FiO2 ratio was 358±126 on TLVbaseline; it decreased to 235±113 on OLVpre‐RM (P<0.01) increased to 351±120 on OLVpost‐RM (P<0.01 vs. OLVpre‐RM), and remain stable thereafter. During the RM, CI decreased from 3.04±0.7 l/m2 OLVpre‐RM to 2.4±0.6 l/m2 (P<0.05), and returned to baseline on OLVpost‐RM (3.1±0.7 l/m2, NS vs. OLVpre‐RM). The RM resulted in alveolar recruitment and caused a significant decrease in static elastance of the dependent lung (16.6±8.9 cmH2O/ml OLVpost‐RM vs. 22.3±8.1 cmH2O/ml OLVpre‐RM) (P<0.01).
Conclusions: During OLV in lateral decubitus for thoracic surgery, application to the dependent lung a recruiting strategy significantly recruits the dependent lung, improving arterial oxygenation and respiratory mechanics until the end of surgery. However, the transient haemodynamic derangement occurring during the RM should be taken into account.
The Single-Nucleotide-Polymorphism (SNP) 118A>G in the μ-1 Opioid Receptor gene (OPRM1) is associated with a decrease in the analgesic effects of opioids. The aim of this study is to assess whether ...118A>G polymorphism could influence the analgesic response to opioid-based postoperative pain (POP) therapy. The study consisted of two parts: section α, observational, included 199 subjects undergoing scheduled surgical procedures with pain management standardized on surgery invasiveness and on expected level of postoperative pain; section β, randomized, included 41 women undergoing scheduled caesarean delivery with continuous intra-operative epidural anesthesia and post-operative analgesia (CEA). In both sections, POP was measured over 48 h (T6h-T24h-T48h) by the visual analogue scale (VAS). In section β we also tested the responsiveness of hypothalamic-pituitary-adrenal axis (HPA) expressed by Cortisol levels. In section α, with cluster analysis, subjects were analyzed according to their genotype: a group (#1) of 34 patients reporting VAS score >3 at every time lapse was identified and included only A118G carriers, while wild-type (A118A - absence of 118A>G polymorphism) patients were unevenly distributed between those with cluster #2 (VAS score <3 at every study steps) and those with cluster #3 (VAS score progressively reducing from T6h). In section (3, A118G carriers receiving epidural sufentanil had the lowest VAS scores at T24h; also in these patients, Cortisol levels remained more stable, with a mild decrease at T6h. This study shows that the OPRM1 118A>G polymorphism affects postoperative pain response in heterozygous patients: they have a different postoperative pain response than patients with wild-type genes, which may affect the efficacy of the analgesic therapy.
In spinal anaesthesia for a Caesarean delivery, it is important to limit anaesthesia only at the surgical area, and to resolve fast motor block. We compared the intraoperative effectiveness, ...hemodynamic effects, anaesthetic recovery times and patients satisfaction after isobaric levobupivacaine (L) 0.25% versus L0.50% spinal anaesthesia during elective Caesarean deliveries performed with the Stark technique.
In this double-blinded prospective study, seventy women undergoing elective caesarean delivery were randomized to receive either intrathecal 7.5 mg Levobupivacaine 0.25% plus sufentanil 2.5 μg (Group L0.25), or intrathecal 7.5 mg L 0.50% plus sufentanil 2.5 μg (GroupControl). The onset time, duration of anaesthesia, analgesia and sensory and motor block and hemodynamic parameters were measured from the beginning of spinal anaesthesia until four hours after spinal anaesthesia (T240).
Onset time, duration of anaesthesia and haemodynamic variations were similar in the two groups. No patients required general anesthesia to complete surgery. Motor block vanished faster in Group L0.25 as compared with GroupControl (p < .01). The cephalad spread of the 0.50% solution was higher than that of the 0.25% solution: no patient in Group L0.25 experienced paresthesia of the upper limbs vs 14% in GroupControl (p < .05). In GroupControl anaesthesia reached the dermatome T1 in 15% of cases. Maternal and surgeon satisfaction was good in every patient.
Levobupivacaine 7.5 milligrams at 0.25% may be used as a suitable alternative to L 0.50% for spinal anaesthesia for caesarean deliveris with the Stark technique with good maternal satisfaction. In Group L0.25 a lower appearance of nausea and hypotension were observed and motor and sensitive block developed and diminished faster while no clinically significant differences in hemodynamic behavior was observed between groups.
Social and cultural factors combined with little information may prevent the diffusion of epidural analgesia for pain relief during childbirth. The present study was launched contemporarily to the ...implementation of analgesia for labor in our Department in order to perform a 2 years audit on its use. The goal is to evaluate the epidural acceptance and penetration into hospital practice by women and care givers and safety and efficacy during childbirth.
This audit cycle measured epidural analgesia performance against 4 standards: (1) Implementation of epidural analgesia for labor to all patients; (2) Acceptance and good satisfaction level reported by patients and caregivers. (3) Effectiveness of labor analgesia; (4) No maternal or fetal side effects.
During the audit period epidural analgesia increased from 15.5% of all labors in the first trimester of the study to 51% in the last trimester (p < 0.005). Satisfaction levels reported by patients and care givers were good. A hierarchical clustering analysis identified two clusters based on VAS (Visual Analogue Scale) time course: in 226 patients (cluster 1) VAS decreased from 8.5±1.4 before to 4.1±1.3 after epidural analgesia; in 1002 patients (cluster 2) VAS decreased from 8.12±1.7 before (NS vs cluster 1), to 0.76±0.79 after (p < 0.001 vs before and vs cluster 2 after). No other differences between clusters were observed.
Present audit shows that the process of implementation of labor analgesia was quick, successful and safe, notwithstanding the identification of one cluster of women with suboptimal response to epidural analgesia that need to be further studies, overall pregnant womens'adhesion to labor analgesia was satisfactory.
Objective: a) to describe a non-barotraumatic ventilatory setting for independent lung ventilation (ILV); b) to determine the utility of single lung end-tidal CO2 (EtCO2) monitoring to evaluate the ...ventilation to perfusion (V/Q) matching in each lung during ILV and for ILV weaning. Design: prospective study. Setting: general intensive care unit in a university teaching hospital. Patients: twelve patients with unilateral thoracic trauma needing ILV. Interventions and results: ILV was started with each lung ventilated with the same tidal volume (Vt): plateau airway pressure (Pplat) was 34.2±3.2 cmH2O in diseased lungs (DL) and 18.1±1.9 cmH2O in normal lungs (NL) (P<0.01). Static compliance (Cst) was 9.9±1.1 ml/cmH2O in DL and 19.3±1.7 ml/cmH2O in NL (P<0.01). EtCO2 was 22.5±2.2 mmHg in DL and 36.6±1.9 mmHg in NL (P<0.01). PaO2/FiO2 was at 151±20. PEEP was applied on the DL and each lung was ventilated with a Vt that developed Pplat ≤26 cmH2O. With this setting, Vt given to the NL was unchanged, whereas it was reduced in the DL (238±30 ml vs 350±31 ml; P<0.01). Cst and EtCO2 were still significantly lower in the DL (P<0.01, respectively), while the PaO2/FiO2 ratio remained unchanged. Vt was then progressively increased in the DL as Pplat decreased, but remained unchanged in the NL. ILV was discontinued when Vt, Cst and EtCO2 were the same in each lung. PaO2/FiO2 ratio had then increased to 295±18. Conclusions: a) during ILV, adequate oxygenation and a reduction in V/Q mismatch can be obtained by setting Vt and PEEP to keep Pplat below a safe threshold for barotrauma; b) measurement of single lung EtCO2 can be useful to evaluate progressive V/Q matching.PUBLICATION ABSTRACT
Background: The cisplatin and gemcitabine (GC) regimen is usually administered as a 4- or 3-week schedule; however, the best schedule to use is still unclear. We therefore started a randomized phase ...II trial to compare toxicity and dose intensity (DI) between these two GC schedules. Patients and methods: Ninety-six patients with non-small-cell lung cancer (NSCLC) and an additional 11 patients with an advanced epithelial neoplasm bladder (n = 5), head and neck (n = 3), cervix (n = 1), esophageal (n = 1) or unknown primary carcinoma (n = 1) were randomized to receive cisplatin 70 mg/m2 intravenously on day 2 plus either gemcitabine 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle or gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle. Planned DI (PDI) for the 4-week schedule was 750 mg/m2/week for gemcitabine and 17.5 mg/m2/week for cisplatin; for the 3-week regimen PDI was 666 mg/m2/week and 23 mg/m2/week for gemcitabine and cisplatin, respectively. Results: From July 1998 to March 2000, 107 patients were randomized. Grade 3/4 neutropenia was observed in 27.8% of patients in the 3-week versus 22.5% in the 4-week arm (P = 0.69), while grade 3/4 thrombocytopenia was higher in the 4-week arm (29.5% versus 5.5% of patients; P = 0.14). A total of 398 cycles of therapy were delivered. Overall, 51% of cycles were modified in dose, timing or both in the 4-week arm, and 19% in the 3-week arm. The 21-day schedule of GC leads to a similar received DI of gemcitabine and higher cisplatin DI. Both regimens had activity in NSCLC, with a response rate of 39% (38% for the 4-week arm, and 42% for the 3-week arm). Conclusions: The 3-week schedule has similar DI to the 4-week schedule. However the 3-week regimen has a better compliance profile and a comparable response rate in NSCLC, supporting the use of such a schedule.
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