The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Prognostic factors in hepatic surgery for colorectal metastasis

Le metastasi epatiche rappresentano la principale causa di decesso nei pazienti con tumore colo-rettale e la chirurgia costituisce l’unica opzione terapeutica in grado di consentire una sopravvivenza a 5 anni compresa tra il 40 % ed il 60 %. Tuttavia, anche quando la resezione epatica si associa a terapia adiuvante, risulta curativa solo nel 20% dei pazienti, con un tasso di recidiva a livello epatico del 70 %. La prognosi dei pazienti con metastasi epatiche da neoplasia colo-rettale è altamente eterogenea ed influenzata da diversi fattori clinici e biologici. Tra i vari sistemi di stratificazione del rischio proposti per individuare la probabilità di recidiva epatica e di sopravvivenza dopo chirurgia delle metastasi epatiche, il “Clinical risk score” proposto da Fong nel 1999 è sicuramente il più utilizzato. Sfortunatamente tutti questi sistemi di stratificazione del rischio prendono in considerazione solo alcuni aspetti clinico-patologici delle metastasi epatiche, permettendo una descrizione solo marginale di questa patologia. Recentemente sono state individuate molteplici nuove caratteristiche istopatologiche dei tumori colo-rettali primitivi, ma solo pochi studi hanno ipotizzato una possibile influenza prognostica di tali fattori sulla chirurgia epatica delle metastasi colo-rettali. Inoltre, i progressi ottenuti negli ultimi anni in termini di nuove tecniche chirurgiche, chemioterapia loco regionale e sistemica e nuove procedure di radiologia interventistica, hanno consentito di ridefinire i criteri di resecabilità delle metastasi epatiche, migliorando l’outcome di pazienti che in passato non sarebbero risultati candidabili a chirurgia. Pertanto risulta necessaria la definizione di nuovi parametri prognostici in grado di selezionare quei pazienti che possono maggiormente beneficiare di un approccio chirurgico alla patologia metastatica epatica in termini di sopravvivenza cancro-specifica, rispetto ad un approccio meno invasivo. Questo studio ha analizzato l’importanza prognostica di selezionate caratteristiche cliniche e istopatologiche relative al tumore colo-rettale primitivo e alle metastasi epatiche in pazienti sottoposti a resezione epatica di metastasi da carcinoma colo-rettale ad intento curativo tra agosto 2005 e marzo 2017 nei reparti di Clinica Chirurgica Generale dell’AOU di Parma. I dati ottenuti sui tassi di sopravvivenza sono sovrapponibili a quanto riportato in letteratura. L’analisi univariata e multivarita delle variabili studiate in rapporto a sopravvivenza globale e sopravvivenza libera da malattia ha evidenziato come l’invasione perineurale nel tumore primitivo possa rappresentare un parametro in grado di influenzare la recidiva dopo epatectomia, mentre il margine epatico positivo dopo resezione può costituire un fattore condizionante la sopravvivenza. Lo studio presenta alcune limitazioni data la natura retrospettiva e il limitato numero di pazienti, che non consentono di generalizzare i risultati ottenuti, pertanto saranno necessari ulteriori studi condotti su gruppi di pazienti più ampi e su database raccolti prospetticamente per poter validare tali risultati

Laparoscopic resection of tailgut cysts: the size is not the issue

INTRODUCTION: Tailgut cysts are rare retrorectal cystic lesions usually treated by surgical resection, even where asymptomatic, due to the risk of malignancy and recurrence. In the last 20 years, the laparoscopic abdominal approach has been gaining consensus for its better visualization of pelvic structures and minimal invasiveness. CASE REPORT: We present the case of the biggest tailgut cysts managed laparoscopically reported so far. DISCUSSION: Mostly asymptomatic, diagnosis of tailgut cysts is often fortuitous during routine examination. Their malignant transformation is estimated being 14.1% of cases. MRI is particularly indicated to lead the surgical approach, given its superior resolution in soft tissues and assessment of local invasion. Surgical resection is the therapy of choice, performed with different approaches: the laparoscopic abdominal technique, performed by surgeons with expertise in pelvic laparoscopic surgery, allows the best visualization of pelvic viscera with lesser morbidity. Due to rupture and seeding risks, the laparoscopic approach should not be performed if there is any suspicion of malignancy. CONCLUSION: Our case substantiates safety and feasibility of laparoscopic tailgut cysts management, even of large-size cysts. Preoperative imaging is crucial to assess the possible malignancy of the lesion and, in that case, to perform a laparotomic approach

Boundary-based analysis for the assessment of coastal dune landscape integrity over time

Coastal dunes are transitional systems which offer manifold ecosystem services, including material and intangible benefits, whose relevance for human society has been little investigated to date. In order to plan a sustainable use of these threatened ecosystems, proper indicators to quantify ecological services and functions over time should be provided. Since the functionality of coastal dunes is affected by the specific contiguity among different dune habitat patches, in this paper we propose the use of landscape integrity, expressed by the number and length of boundary types among the aforementioned habitats, as an ecosystem functionality indicator. In particular, we aim at properly expressing the trend of coastal dune mosaic integrity in two Italian LTER sites over the last sixty years by applying a generalized diversity function on the number and length of boundary types. Such functions, unlike a traditional diversity index, allow a complete summarization of landscape diversity and structure. The proposed method has proved to be effective in the considered context, because it has adequately underlined the different landscape integrity trend recorded in the two sites. In particular, generalized diversity functions showed to efficiently express both rough and moderate anthropogenic transformations, which affected spatial heterogeneity and functionality of the considered coastal dune mosaic. Further applications at different scales and across different ecosystems are encouraged

Minimally invasive esophagectomy for caustic ingestion after 73 years and over 200 endoscopic dilations: Is it just a matter of time?

Refractory esophageal strictures are a common sequela of caustic ingestion. If endoscopic dilation becomes ineffective, esophagectomy represents the only therapeutic option. The minimally invasive approach, specifically the thoracoscopic access in prone position, may allow postoperative morbidity to be reduced. We present the first case described in the Literature of minimally invasive esophagectomy in prone position for a long-term failure of endoscopic dilation after caustic ingestion. (www.actabiomedica.it

Nurses’ Readiness to Undertake Controlled Negative Pressure Therapy in the Treatment of Chronic Wounds—Research Report

Local wound treatment with negative pressure wound therapy (NPWT) shortens the healing process but requires the supervision of trained medical personnel for administering the therapeutic procedures. Professional supervision and control of the effectiveness of NPWT, as well as education conducted by nurses, are of particular importance for therapeutic and caring processes, both in hospital and at home. The aim of the study was the assessment of the perception of NPWT by certified nurses in the topical treatment of chronic wounds. The study was conducted using the method of estimation and a diagnostic survey with the proprietary NPWT perception questionnaire: 495 subjects were enrolled in the study and 401 respondents aged 25–67 years qualified for statistical analysis. Despite their experience and competence, the respondents critically assessed their knowledge, pointing to an average subjective level of knowledge related to wound treatment and a low level of knowledge related to NPWT. Most of the respondents had no experience of independent treatment using this method. The data obtained from the questionnaire clearly indicate theoretical preparation and high motivation to undertake activities related to the implementation of NPWT in their own practice. Low readiness values suggested that the subjects did not have the resources or the ability to implement the method. The perception of NPWT in the surveyed group of nurses was determined by numerous factors, including self-assessment of their own knowledge, motivation and readiness to use NPWT. A high level of NPWT perception was noted, despite low motivation related to the availability and knowledge of the method. Theoretical knowledge is insufficient to implement innovative methods in local wound treatment. Practical skills and motivation are indispensable elements that should be met during the training and education of nurses in the field of wound care