Enhanced recovery pathways in thoracic surgery from Italian VATS group: preoperative optimisation

Abstract: Preoperative patient optimisation is a key point of enhanced recovery after thoracic surgery pathways. This could be particularly advantageous when considering video-assisted thoracic surgery (VATS) lobectomy, because reduced trauma related to minimally invasive techniques is one of the main factors favouring improved postoperative outcome. Main specific interventions for clinical optimisation before major lung resection include assessment and treatment of comorbidities, minimizing preoperative hospitalization, optimisation of pharmacological prophylaxis (antibiotic and thromboembolic) and minimizing preoperative fasting. Literature data and clinical evidences in this setting are reported and discussed

Relevance of pharmacogenomics and multidisciplinary management in a young-elderly patient with KRAS mutant colorectal cancer treated with first-line aflibercept-containing chemotherapy

Introduction: Intensive oncological treatment integrated with resection of metastases raised the clinical outcome of metastatic colorectal cancer (MCRC). In clinical practice, complex evaluation of clinical (age, performance status, comorbidities), and biological (tumoral genotype, pharmacogenomic) parameters addresses tailored, personalized multidisciplinary treatment strategies. Patients with MCRC unsuitable for first-line intensive medical treatments are prevalent and showed worse clinical outcome. After progression to oxaliplatin-based chemotherapy, aflibercept/FOLFIRI significantly improved clinical outcome, even if no survival benefit was reported in adjuvant fast relapsers by aflibercept addition. The case reported a young-elderly (yE) patient with KRAS mutant colorectal cancer rapidly progressing to adjuvant chemotherapy, unfit owing to comorbidities, with multiple pharmacogenomic alterations, who gained long-term survival in clinical practice by multidisciplinary treatment strategy consisting of first-line and re-introduction of aflibercept-containing chemotherapy and two-stage lung metastasectomies. Case presentation: A 71-years-old yE patient, unfit for intensive oncological treatments owing to Cumulative Illness Rating Scale (CIRS) stage secondary, affected by KRAS c.35 G>T mutant colorectal cancer, rapidly progressing with lung metastases after adjuvant XelOx chemotherapy, reached long-term survival 66 months with no evidence of disease after first-line and re-introduction of tailored, modulated aflibercept (4 mg/kg) d1,15-irinotecan (120 mg/m2) d1,15-5-fluorouracil (750 mg/m2 /day) dd1–4, 15–18; and secondary radical bilateral two-stage lung metastasectomies. Safety profile was characterized by limiting toxicity syndrome at multiple sites (LTS-ms), requiring 5-fluorouracil discontinuation and aflibercept reduction (2 mg/kg), because of G2 hand-foot syndrome (HFS) for >2 weeks, and G3 hypertension. Pharmacogenomic analyses revealed multiple alterations of fluoropyrimidine and irinotecan metabolism: severe deficiency of fluorouracil degradation rate (FUDR), single nucleotide polymorphisms of UGT1A1* 28 variable number of tandem repeats (VNTR) 7R/7R homozygote, ABCB1 c.C3435T, c.C1236T, MTHFR c.C667T homozygote, DPYD c.A166G, TSER 28bp VNTR 2R/3R heterozygote. Conclusions: In clinical practice, a complex management evaluating clinical parameters and RAS/BRAF genotype characterizing an individual patient with MCRC, particularly elderly and/or unfit owing to comorbidities, is required to properly address tailored, multidisciplinary medical and surgical treatment strategies, integrated with careful monitoring of superimposing toxicity syndromes, also related to pharmacogenomic alterations, to gain optimal activity, and long-term efficacy

The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer

Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches

Value of multidetector computed tomography image segmentation for preoperative planning in general surgery

Using practical examples, this report aims to highlight the clinical value of patient-specific three-dimensional (3D) models, obtained segmenting multidetector computed tomography (MDCT) images, for preoperative planning in general surgery.In this study, segmentation and 3D model generation were performed using a semiautomatic tool developed in the authors' laboratory. Their segmentation procedure is based on the neighborhood connected region-growing algorithm that, appropriately parameterized for the anatomy of interest and combined with the optimal segmentation sequence, generates good-quality 3D images coupled with facility of use. Using a touch screen monitor, manual refining can be added to segment structures unsuitable for automatic reconstruction. Three-dimensional models of 10 candidates for major general surgery procedures were presented to the operating surgeons for evaluation. A questionnaire then was administered after surgery to assess the perceived added value of the new technology.The questionnaire results were very positive. The authors recorded the diffuse opinion that planning the procedure using a segmented data set allows the surgeon to plan critical interventions with better awareness of the specific patient anatomy and consequently facilitates choosing the best surgical approach.The benefit shown in this report supports a wider use of segmentation software in clinical practice, even taking into account the extra time and effort required to learn and use these systems

Southern Ocean carbon sink enhanced by sea-ice feedbacks at the Antarctic Cold Reversal

The Southern Ocean occupies some 14% of the planet’s surface and plays a fundamental role in the global carbon cycle and climate. It provides a direct connection to the deep ocean carbon reservoir through biogeochemical processes that include surface primary productivity, remineralisation at depth, and the upwelling of carbon-rich water masses. However, the role of these different processes in modulating past and future air-sea carbon flux remains poorly understood. A key period in this regard is the Antarctic Cold Reversal (ACR, 14.6-12.7 kyr BP), a period of mid- to high-latitude cooling that coincided with a sustained plateau in deglacial atmospheric rise in CO2 globally. Here we reconstruct high-latitude Southern Ocean surface productivity from marine derived aerosols captured in a highly-resolved horizontal ice core. Our multiproxy reconstruction reveals a coherent signal of enhanced productivity across the ACR. Transient climate modelling indicates this period coincided with maximum seasonal variability in sea-ice extent, implying that sea-ice biological feedbacks enhanced CO2 sequestration, creating a significant regional marine carbon sink that contributed to the sustained plateau in CO2 at the ACR. Our results highlights the role Antarctic sea ice plays in controlling global CO2, and demonstrates the need to incorporate such feedbacks in climate-carbon models

Multidisciplinary International Conference on Gynecologic Cancer, Bologna, June 8-12, 2005.

The first "Multidisciplinary International Conference on Gynecologic Cancer" which was held in Bologna on June 8-12, 2005, addressed some of the most crucial topics in gynecologic oncology, presented the latest achievements and, at the same time, designed the guidelines for future developments in the field. The scientific program was intended not only to share and compare views and ideas among gynecologists but also with oncologists and researchers in basic science. The scientific committee strongly believed in the "multidisciplinary approach" towards medicine and particularly towards patients