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

Parenchymal sparing surgery for lung cancer: focus on pulmonary artery reconstruction

Simple Summary Reconstruction of the pulmonary artery associated with lobectomy for the radical resection of lung cancer is a safe and effective therapeutic option that may allow radical resection when lobectomy is not technically feasible, avoiding pneumonectomy. This review addresses some controversial aspects concerning the intraoperative and perioperative management of a sleeve resection with pulmonary artery reconstruction that may influence the outcome. Pulmonary artery reconstruction associated with lobectomy is a safe and viable parenchymal sparing intervention to radically treat lung cancer, allowing better long-term survival, lower perioperative morbidity and mortality rates and functional benefits if compared with PN. Reconstruction of the pulmonary artery (PA) associated with lobectomy for the radical resection of lung cancer has been progressively gaining diffusion in lung cancer surgery as a safe and effective therapeutic option that may allow radical resection when lobectomy is not technically feasible, avoiding pneumonectomy. There are some controversial aspects concerning the intraoperative and perioperative management of a sleeve resection with PA reconstruction that may influence the outcome. In the present article, the authors have analyzed some of the main technical and oncological aspects to take stock of what they have learned from their lung-sparing operations experience over time. PA reconstruction may require prosthetic materials including different options with variable cost. A main concern in vascular reconstructive procedures is avoiding tension on the anastomosis. When PA reconstruction is required, appropriate anticoagulation management is crucial. Results from the main literature data confirm the reliability of lobectomy associated with PA reconstruction in terms of perioperative morbidity and long-term survival. Sleeve lobectomy and PA reconstruction can be performed safely and effectively even after induction therapy

Salvage resection of advanced mediastinal tumors

The surgical treatment of locally advanced mediastinal tumors invading the great vessels and other nearby structures still represent a tricky question, principally due to the technical complexity of the resective phase, the contingent need to carry out viable vascular reconstructions and, therefore, the proper management of pathophysiologic issues. Published large-number series providing oncologic outcomes of patients who have undergone extended radical surgery for invasive mediastinal masses are just a few. Furthermore, the wide variety of different histologies included in some of these studies, as well as the heterogeneity of chemo and radiation therapies employed, did not allow for the development of clear oncologic guidelines. Usually in the past, surgical resections of large masses along with the neighbouring structures were not offered to patients because of related morbidity and mortality and limited information available on the prognostic advantage for long term. However, in the last decades, advances in surgical technique and perioperative management, as well as increased oncologic experience in this field, have allowed radical exeresis in selected patients with invasive tumors requiring resections extended to the surrounding structures and complex vascular reconstructions. Such aggressive surgical treatment has been proposed in association or not with adjuvant chemo- or radiotherapy regimens, achieving encouraging oncologic results with limited morbidity and mortality in experienced institutions. Congestive heart failure or impending cardiovascular collapse due to the compression by the large mass are the most frequent immediately lifethreatening problems that some of these patients can experience. In this setting, medical palliation is usually ineffective and an aggressive salvage surgical treatment may remain the only therapeutic option

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

RIVERINE DISSOLVED ORGANIC MATTER DECOMPOSITION AND DYNAMICS

Aquatic and terrestrial ecosystems are intimately linked through the transfer of energy and materials. A common example of ecosystem linkage is the input of terrestrial dissolved organic matter (DOM) to rivers and streams. DOM can play a variety of roles in stream ecosystem function by fueling local food webs, influencing trophic state, and affecting the dissolved nutrient availability. Microorganisms utilize, transform, and produce DOM during microbial metabolism, a relationship that links microbes to DOM quality and quantity. Chemical and physical properties are known to vary with DOM source, and thus the type of terrestrial input may dictate how DOM is processed in a stream.  Using laboratory microcosms, and added terrestrial organic matter substrates, we carried out a leaching experiment over forty-five days. We employed a suite of complementary techniques to determine the effect of leaching DOM sources on microorganisms, DOM processing, and ecosystem function.  Microbial community composition changed from the original stream water inoculum and depended on DOM source. Cell abundances for all DOM sources spiked after two days, after which abundances dropped and remained relatively steady until the end of the experiment.  DOM concentrations decreased exponentially with the maximum amount of carbon utilization taking place within the first five days.  The DOM fluorescent signature, initially influenced by amino acid-like fluorescence shifts to more humic-like character over the course of the experiment, indicating DOM humification over time. Our results showcase the advantages of interdisciplinary tools to elucidate the connection of microbial processing, DOM chemistry, and ecosystem function

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

Cyclin D1 Expression and the Inhibitory Effect of Celecoxib on Ovarian Tumor Growth in Vivo

The report aims to investigate the relationship between the expression of cyclin D1 and Cyclooxgenase-2 (COX-2), thus to explore the molecular mechanisms of the antitumor efficacy of Celecoxib, a COX-2 inhibitor. Human ovarian SKOV-3 carcinoma cell xenograft-bearing mice were treated with Celecoxib by infusing gaster (i.g.) twice/day for 21 days. The mRNA levels of COX-2 and cyclin D1 were determined by RT-PCR. The expression of cyclin D1 at the protein level was detected by immunohistochemistry, while COX-2 protein expression was determined by Western blot. A high-dose of Celecoxib (100 mg/kg) significantly inhibited tumor growth (P < 0.05), and the expression of cyclin D1 was reduced by 61%. Celecoxib decreased the proliferation cell index by 40% (P < 0.001) and increased apoptotic index by 52% (P < 0.05) in high-dose Celecoxib treated group. Our results suggest that the antitumor efficacy of Celecoxib against ovarian cancer in mice may in part be mediated through suppression of cyclin D1, which may contribute to its ability to suppress proliferation

Machine-learning based approach to examine ecological processes influencing the diversity of riverine dissolved organic matter composition

Dissolved organic matter (DOM) assemblages in freshwater rivers are formed from mixtures of simple to complex compounds that are highly variable across time and space. These mixtures largely form due to the environmental heterogeneity of river networks and the contribution of diverse allochthonous and autochthonous DOM sources. Most studies are, however, confined to local and regional scales, which precludes an understanding of how these mixtures arise at large, e.g., continental, spatial scales. The processes contributing to these mixtures are also difficult to study because of the complex interactions between various environmental factors and DOM. Here we propose the use of machine learning (ML) approaches to identify ecological processes contributing toward mixtures of DOM at a continental-scale. We related a dataset that characterized the molecular composition of DOM from river water and sediment with Fourier-transform ion cyclotron resonance mass spectrometry to explanatory physicochemical variables such as nutrient concentrations and stable water isotopes (2H and 18O). Using unsupervised ML, distinctive clusters for sediment and water samples were identified, with unique molecular compositions influenced by environmental factors like terrestrial input and microbial activity. Sediment clusters showed a higher proportion of protein-like and unclassified compounds than water clusters, while water clusters exhibited a more diversified chemical composition. We then applied a supervised ML approach, involving a two-stage use of SHapley Additive exPlanations (SHAP) values. In the first stage, SHAP values were obtained and used to identify key physicochemical variables. These parameters were employed to train models using both the default and subsequently tuned hyperparameters of the Histogram-based Gradient Boosting (HGB) algorithm. The supervised ML approach, using HGB and SHAP values, highlighted complex relationships between environmental factors and DOM diversity, in particular the existence of dams upstream, precipitation events, and other watershed characteristics were important in predicting higher chemical diversity in DOM. Our data-driven approach can now be used more generally to reveal the interplay between physical, chemical, and biological factors in determining the diversity of DOM in other ecosystems