Outcomes of Radiofrequency Ablation for Dysplastic Barrett’s Esophagus: A Comprehensive Review

Barrett's esophagus is a condition in which the normal squamous lining of the esophagus has been replaced by columnar epithelium containing intestinal metaplasia induced by recurrent mucosal injury related to gastroesophageal reflux disease. Barrett's esophagus is a premalignant condition that can progress through a dysplasia-carcinoma sequence to esophageal adenocarcinoma. Multiple endoscopic ablative techniques have been developed with the goal of eradicating Barrett's esophagus and preventing neoplastic progression to esophageal adenocarcinoma. For patients with high-grade dysplasia or intramucosal neoplasia, radiofrequency ablation with or without endoscopic resection for visible lesions is currently the most effective and safe treatment available. Recent data demonstrate that, in patients with Barrett's esophagus and low-grade dysplasia confirmed by a second pathologist, ablative therapy results in a statistically significant reduction in progression to high-grade dysplasia and esophageal adenocarcinoma. Treatment of dysplastic Barrett's esophagus with radiofrequency ablation results in complete eradication of both dysplasia and of intestinal metaplasia in a high proportion of patients with a low incidence of adverse events. A high proportion of treated patients maintain the neosquamous epithelium after successful treatment without recurrence of intestinal metaplasia. Following successful endoscopic treatment, endoscopic surveillance should be continued to detect any recurrent intestinal metaplasia and/or dysplasia. This paper reviews all relevant publications on the endoscopic management of Barrett's esophagus using radiofrequency ablation

Hepatic resection for hepatocellular carcinoma in patients with Child–Pugh's A cirrhosis: is clinical evidence of portal hypertension a contraindication?

AbstractBackgroundAccording to international guidelines [European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD)], portal hypertension (PHTN) is considered a contraindication for liver resection for hepatocellular carcinoma (HCC), and patients should be referred for other treatments. However, this statement remains controversial. The aim of this study was to elucidate surgical outcomes of minor hepatectomies in patients with PHTN (defined by the presence of esophageal varices or a platelet count of <100 000 in association with splenomegaly) and well‐compensated liver disease.MethodsBetween 1997 and 2012, a total of 223 cirrhotic patients [stage A according to the Barcelona Clinic Liver Cancer (BCLC) classification] were eligible for this analysis and were divided into two groups according to the presence (n = 63) or absence (n = 160) of PHTN. The demographic data were comparable in the two patient groups.ResultsOperative mortality was not different (only one patient died in the PHTN group). However, patients with PHTN had higher liver‐related morbidity (29% versus 14%; P = 0.009), without differences in hospital stay (8.8 versus 9.8 days, respectively). The PHTN group showed a worse survival rate only if biochemical signs of liver decompensation existed. Multivariate analysis identified albumin levels as an independent predictive factor for survival.ConclusionsPHTN should not be considered an absolute contraindication to a hepatectomy in cirrhotic patients. Patients with PHTN have short‐ and long‐term results similar to patients with normal portal pressure. A limited hepatic resection for early‐stage tumours is an option for Child–Pugh class A5 patients with PHTN

The Causal Effects of Income Support and Housing Benefits on Mental Well-Being: An Application of a Bayesian Network

© 2016 John Wiley & Sons Ltd. This study explores the causal effects of air pollution, income support, housing benefits and household income on the subjective mental well-being in United Kingdom (UK). Additionally, the analysis considers the effects of air pollution and weather conditions. The estimates are based on data from the British Household Panel Survey. The results show that those who are unemployed or who have a low income and who claim the benefits report higher levels of mental well-being than those who do not claim them. Moreover, the marginal willingness to pay (MWTP) for an improvement on air quality are lower in the case of the Bayesian Network

Constitutional mismatch repair deficiency–associated brain tumors: report from the European C4CMMRD consortium

Abstract Background Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European "Care for CMMRD" (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment. Methods Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017. Results Among the 87 registered patients, 49 developed 56 malignant BTs: 50 high-grade gliomas (HGG) (with giant multinucleated cells in 16/21 histologically reviewed tumors) and 6 embryonal tumors. The median age at first BT was 9.2 years [1.1–40.6], with nine patients older than 18. Twenty-seven patients developed multiple malignancies (including16 before the BT). Most patients received standard treatment, and eight patients immunotherapy for relapsed HGG. The 3- and 5-year overall survival (OS) rates were 30% (95% CI: 19–45) and 22% (95% CI: 12–37) after the first BT, with worse prognosis for HGG (3-year OS = 20.5%). Six patients were alive (median follow-up 2.5 years) and 43 dead (38 deaths, 88%, were BT-related). Other CMMRD-specific features were café-au-lait macules (40/41), multiple BTs (5/15), developmental brain anomalies (11/15), and consanguinity (20/38 families). Conclusions Several characteristics could help suspecting CMMRD in pediatric malignant BTs: giant cells on histology, previous malignancies, parental consanguinity, café-au-lait macules, multiple BTs, and developmental brain anomalies. The prognosis of CMMRD-associated BT treated with standard therapies is poor requiring new therapeutic up-front approaches

NF1 optic pathway glioma. Analysing risk factors for visual outcome and indications to treat

BackgroundThe aim of the project was to identify risk factors associated with visual progression and treatment indications in pediatric patients with Neurofibromatosis type 1 associated optic pathway gliomas (NF1-OPG).MethodsA multi-disciplinary expert group consisting of ophthalmologists, pediatric neuro-oncologists, neurofibromatosis specialists and neuro-radiologists involved in therapy trials assembled a cohort of children with NF1-OPG from six European countries with complete clinical, imaging and visual outcome datasets. Using methods developed during a consensus workshop, visual and imaging data were reviewed by the expert team and analyzed to identify associations between factors at diagnosis with visual and imaging outcomes.Results83 patients (37 males, 46 females, mean age 5.1±2.6 years; 1-13.1 years) registered in the European treatment-trial SIOP LGG-2004 (recruited 2004-2012) were included. They were either observed or treated (at diagnosis/ after follow-up).In multivariable analysis, factors present at diagnosis associated with adverse visual outcomes included: multiple visual signs and symptoms (adjOR 8.33, 95%CI 1.9-36.45); abnormal visual behavior (adjOR 4.15, 95%CI 1.20-14.34); new onset of visual symptoms (adjOR 4.04, 95%CI 1.26-12.95) and optic atrophy (adjOR 3.73, 95%CI 1.13-12.53). Squint, posterior visual pathway tumor involvement, and bilateral pathway tumor involvement, showed borderline significance. Treatment appeared to reduce tumor size but improved vision in only 10/45 treated patients. Children with visual deterioration after primary observation are more likely to improve with treatment than children treated at diagnosis.ConclusionsThe analysis identified the importance of symptomatology, optic atrophy and history of vision loss as predictive factors for poor visual outcomes in children with NF1-OPG

A nationwide evaluation of bevacizumab-based treatments in pediatric low-grade glioma in the UK: safety, efficacy, visual morbidity, and outcomes

BACKGROUND: Bevacizumab is increasingly used in children with pediatric low-grade glioma (PLGG) despite limited evidence. A nationwide UK service evaluation was conducted to provide larger cohort "real life" safety and efficacy data including functional visual outcomes. METHODS: Children receiving bevacizumab-based treatments (BBT) for PLGG (2009-2020) from 11 centers were included. Standardized neuro-radiological (RANO-LGG) and visual (logMAR visual acuity) criteria were used to assess clinical-radiological correlation, survival outcomes and multivariate prognostic analysis. RESULTS: Eighty-eight children with PLGG received BBT either as 3rd line with irinotecan (85%) or alongside 1st/2nd line chemotherapies (15%). Toxicity was limited and minimal. Partial response (PR, 40%), stable disease (SD, 49%), and progressive disease (PD, 11%) were seen during BBT. However, 65% progressed at 8 months (median) from BBT cessation, leading to a radiology-based 3 yr-progression-free survival (PFS) of 29%. Diencephalic syndrome (P = .03) was associated with adverse PFS. Pre-existing visual morbidity included unilateral (25%) or bilateral (11%) blindness. Improvement (29%) or stabilization (49%) of visual acuity was achieved, more often in patients' best eyes. Vision deteriorated during BBT in 14 (22%), with 3-year visual-PFS of 53%; more often in patients' worst eyes. A superior visual outcome (P = .023) was seen in neurofibromatosis type 1-associated optic pathway glioma (OPG). Concordance between visual and radiological responses was 36%; optimized to 48% using only best eye responses. CONCLUSIONS: BBTs provide effective short-term PLGG control and delay further progression, with a better sustained visual (best > worst eye) than radiological response. Further research could optimize the role of BBT toward a potentially sight-saving strategy in OPG

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Children with Neurofibromatosis type 1 and Optic Pathway Glioma: a collaborative research to design innovative clinical trials based on functional outcomes

Neurofibromatosis type 1 associated optic pathway gliomas (OPG) are relatively frequent (10-15%) among childhood low-grade glioma (LGG), the most common pediatric brain tumor neoplasm. Overall therapeutic strategy includes the use of first line chemotherapy for progressive tumor and has shown to be well tolerated and effective to control tumor growth, considering a 5 yrs-PFS of 74.5%, in the prospective SIOP-LGG NF1+ 2004 study data. However, preliminary data regarding visual outcome reveal how, despite good tumor control rate, the functional outcome of many children with NF1 OPG is still unsatisfactory. In fact from the SIOP prospective series, about 45% of children treated with chemotherapy had a bilaterally compromised visual acuity at last follow-up, with some degree of visual improvement in a minority of children. These data pinpoint the importance of considering vision rather than radiology as a primary outcome measure in these patients. Prognostic factors analysis showed that surgery is a risk factor for worse PFS. These data failed to demonstrate significant differences by age, gender, tumor site, indication to treatment. A retrospective study was undertaken during the French period at the Institut Gustave Roussy to identify possible radiology factors that may predict response to chemotherapy. Results have shown that OPG involving the optic radiation (PLAN 4) and multi-site tumors have a worse response to chemotherapy. The prognostic impact of these factors needs to be confirmed in a larger and prospective population. A multidisciplinary workshop was held in Europe, with the aim to analyse case by case, clinical presentation and radiological tumor aspects. From this clinical ground we tried to analyse factors influencing the risk of progression and the possible benefit of chemotherapy. We discussed and proposed factors determining treatment indication according to a risk-based strategy. This strategy includes an observation arm for children at low risk, a randomization between observation and treatment in children at uncertain or intermediate risk and a further, multiple treatments randomized arm for children at high risk. This innovative multi-arms multi-stage (MAMS) study design will speed up the results of randomised trials by “picking the winner” between multiple arms by interim analysis and will reduce number of patient required to answer scientific questions for such rare diseases. A US-lead NF1 OPG natural history study with the aim to develop evidence based criteria for treatment indication, to which European Centres will collaborate, will prospectively generate additional information that could implement and modify this risk based proposed strategy within the next years. The collaborative guideline for visual assessment and visual outcome interpretation in OPG clinical trials is presented. Visual outcome, based on a standardized visual assessment, will be the primary outcome of new trials evaluating treatment efficacy, in children with NF1 OPG. These aspects are of paramount relevance for a successful interpretation and comparison of data from the upcoming international studies.I gliomi delle vie ottiche (OPG) associati a neurofibromatosi di tipo 1 (NF1) rappresentano il 10-15% dei gliomi a basso grado (LGG), che sono i tumori del sistema nervosa centrale più frequenti in età pediatrica. La strategia terapeutica attuale che prevede l’utilizzo di chemioterapia ha dimostrato dai dati dello studio europeo SIOP-LGG2004 NF1+ una sopravvivenza libera da malattia pari a circa 74.5% a cinque anni. Dai dati preliminari analizzati, tuttavia, gli esiti funzionali in termini di deficit visivo sono ancora poco studiati. I dati preliminari di funzionalità visiva, mostrano che l’acuità visiva migliora in 23% dei pazienti e fino a metà (46%) dei bambini trattati con chemioterapia presentano una visione compromessa alla fine del follow-up. Tali dati dimostrano che nonostante una buona sopravvivenza libera da malattia l’outcome visivo sia insoddisfacente e sottolineano l’importanza di documentare ed analizzare la funzionalità visiva quale end point primario. Non è chiaro quali possano essere i fattori che influenzano il rischio di perdita del visus e quali pazienti possano beneficiare dal trattamento chemioterapico attuale. Uno studio retrospettivo mono istituzionale, condotto durante la permanenza presso il centro di oncologia Institut Gustave Roussy (Francia), ha cercato di identificare la presenza di fattori radiologici distinti e associati a una diversa risposta alla chemioterapia nei bambini affetti da OPG e NF1. I dati dello studio dimostrano che la presenza di un glioma esteso alle regioni esterne alle vie ottiche (multicentrico) sia associato a una risposta meno favorevole alla chemioterapia. Un coinvolgimento delle regioni delle radiazioni ottiche (PLAN 4) sembra inoltre in parte responsabile di una prognosi peggiore. È possibile utilizzare i criteri radiologici identificati per confermare i dati dello studio pilota su casistiche più ampie. Un workshop multidisciplinare, condotto a livello europeo ha permesso di analizzare i dati clinici e radiologici di una popolazione selezionata di bambini con NF1 e OPG, rivedendo a priori e posteriori i fattori che possano influenzare le indicazioni alla chemioterapia o all’osservazione, con l’obiettivo di individuare possibili fattori di rischio per un deficit visivo da un lato e, dall’altro, i fattori associati a un possibile beneficio del trattamento chemioterapico. La funzione visiva iniziale, l’estensione del tumore, l’evoluzione clinica e radiologica sono i criteri sui quali è basata la selezione dei pazienti in diversi gruppi di rischio. Su questi criteri è stata elaborata una strategia terapeutica innovativa, che comprende un braccio osservazionale per i pazienti definiti a basso rischio (gruppo A) mentre una randomizzazione tra osservazione e trattamento è prevista per i pazienti del gruppo di rischio intermedio (gruppo B). Per i pazienti del gruppo B, randomizzati a ricevere il trattamento e per quelli ad alto rischio (gruppo C) candidati invece direttamente a ricevere il trattamento, una successiva randomizzazione a tre diversi bracci di chemioterapia comprendenti un braccio con una terapia biologica è stata elaborata grazie all’utilizzo di una metodologia statistica innovativa (MAMS). Tale metodologia statistica dovrebbe permettere di valutare in contemporanea più di due bracci di trattamento randomizzati e di scartare il peggiore (o selezionare il migliore), riducendo la numerosità necessaria per le risposte ai quesiti dello studio. Uno studio prospettico condotto dai colleghi nordamericani su bambini con NF1 e nuova diagnosi di OPG dovrebbe permettere di validare i fattori prognostici noti e/o individuare ulteriori possibili fattori che influenzano le indicazioni al trattamento e l’outcome visivo. Il gruppo europeo sta valutando la partecipazione a tale studio che arruolerà i pazienti nei prossimi 2-3 anni, con l’obiettivo di implementare i criteri di rischio proposti nello studio europeo futuro. Infine è stato presentato il lavoro collaborativo di stesura delle linee guida proposte, in corso di approvazione dal gruppo europeo, per la valutazione standardizzata della funzionalità visiva e l’interpretazione clinica e statistica dell’outcome visivo, principale end-point funzionale proposto nel prossimo studio in bambini affetti da NF1 e OPG