Introduction
The incidence of gastrointestinal (GI) cancer is rising and most patients with GI malignancies are discussed by a multidisciplinary team (MDT). We performed a systematic review to assess ...whether MDTs for patients with GI malignancies can correctly change diagnosis, tumor stage and subsequent treatment plan, and whether the treatment plan was implemented.
Methods
We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a search of the PubMed, MEDLINE and EMBASE electronic databases, and included studies relating to adults with a GI malignancy discussed by an MDT prior to the start of treatment which described a change of initial diagnosis, stage or treatment plan. Two researchers independently evaluated all retrieved titles and abstracts from the abovementioned databases.
Results
Overall, 16 studies were included; the study quality was rated as fair. Four studies reported that MDTs changed the diagnoses formulated by individual physicians in 18.4–26.9% of evaluated cases; two studies reported that MDTs formulated an accurate diagnosis in 89 and 93.5% of evaluated cases, respectively; nine studies described that the treatment plan was altered in 23.0–41.7% of evaluated cases; and four studies found that MDT decisions were implemented in 90–100% of evaluated cases. The reasons for altering a treatment plan included the patient’s wishes, and comorbidities.
Conclusions
MDT meetings for patients with a GI malignancy are responsible for changes in diagnoses and management in a significant number of patients. Treatment plans formulated by MDTs are implemented in 90–100% of discussed patients. All patients with a GI malignancy should be discussed by an MDT.
Simplified SIMPs and the LHC Daci, N.; De Bruyn, I.; Lowette, S. ...
The journal of high energy physics,
11/2015, Letnik:
2015, Številka:
11
Journal Article
Recenzirano
Odprti dostop
A
bstract
The existence of Dark Matter (DM) in the form of Strongly Interacting Massive Particles (SIMPs) may be motivated by astrophysical observations that challenge the classical Cold DM scenario. ...Other observations greatly constrain, but do not completely exclude, the SIMP alternative. The signature of SIMPs at the LHC may consist of neutral, hadron-like, trackless jets produced in pairs. We show that the absence of charged content can provide a very efficient tool to suppress dijet backgrounds at the LHC, thus enhancing the sensitivity to a potential SIMP signal. We illustrate this using a simplified SIMP model and present a detailed feasibility study based on simulations, including a dedicated detector response parametrization. We evaluate the expected sensitivity to various signal scenarios and tentatively consider the exclusion limits on the SIMP elastic cross section with nucleons.
Background/Aims Primary sclerosing cholangitis (PSC) patients are at risk for developing cholangiocarcinoma (CCA) and colorectal carcinoma (CRC). Our aim was to assess the risk of malignancies and ...their influence on survival. Methods Data from PSC patients diagnosed between 1980 and 2006 in two university hospitals were retrieved. The Kaplan–Meier method and a time-dependent Cox regression model were used to calculate risks of malignancies and their influence on survival. Results Two hundred and eleven patients were included, 143 (68%) were male and 126 (60%) had inflammatory bowel disease (IBD). Median transplantation-free survival was 14 years. The risk of CCA after 10 and 20 years was 9% and 9%, respectively. In patients with concomitant IBD the 10-year and 20-year risks for CRC were 14% and 31%, which was significantly higher than for patients without IBD (2% and 2% ( P = 0.008)). CCA, cholangitis, and age at entry were independent risk factors for the combined endpoint death or liver transplantation. Risk factors for the endpoint death were CCA, CRC, age, and symptomatic presentation. Conclusions Patients with PSC and IBD have a high long-term risk of developing CRC and this risk is about threefold higher than the risk for CCA. Both malignancies are associated with decreased survival.
Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants in the fumarate hydratase (
FH
) gene. It is ...characterized by cutaneous and uterine leiomyomas and an increased risk of developing renal cell carcinoma (RCC), which is usually adult-onset. HLRCC-related RCC tends to be aggressive and can metastasize even when the primary tumor is small. Data on children and adolescents are scarce. Herein, we report two patients from unrelated Dutch families, with HLRCC-related RCC at the ages of 15 and 18 years, and a third patient with an
FH
mutation and complex renal cysts at the age of 13. Both RCC’s were localized and successfully resected, and careful MRI surveillance was initiated to monitor the renal cysts. One of the patients with RCC subsequently developed an ovarian Leydig cell tumor. A review of the literature identified 10 previously reported cases of HLRCC-related RCC in patients aged younger than 20 years, five of them presenting with metastatic disease. These data emphasize the importance of recognizing HLRCC in young patients to enable early detection of RCC, albeit rare. They support the recommendations from the 2014 consensus guideline, in which genetic testing for
FH
mutations, and renal MRI surveillance, is advised for HLRCC family members from the age of 8–10 years onwards.
Immunotherapy holds great promise for the treatment of pediatric cancers. In neuroblastoma, the recent implementation of anti-GD2 antibody Dinutuximab into the standard of care has improved patient ...outcomes substantially. However, 5-year survival rates are still below 50% in patients with high-risk neuroblastoma, which has sparked investigations into novel immunotherapeutic approaches. T cell-engaging therapies such as immune checkpoint blockade, antibody-mediated therapy and adoptive T cell therapy have proven remarkably successful in a range of adult cancers but still meet challenges in pediatric oncology. In neuroblastoma, their limited success may be due to several factors. Neuroblastoma displays low immunogenicity due to its low mutational load and lack of MHC-I expression. Tumour infiltration by T and NK cells is especially low in high-risk neuroblastoma and is prognostic for survival. Only a small fraction of tumour-infiltrating lymphocytes shows tumour reactivity. Moreover, neuroblastoma tumours employ a variety of immune evasion strategies, including expression of immune checkpoint molecules, induction of immunosuppressive myeloid and stromal cells, as well as secretion of immunoregulatory mediators, which reduce infiltration and reactivity of immune cells. Overcoming these challenges will be key to the successful implementation of novel immunotherapeutic interventions. Combining different immunotherapies, as well as personalised strategies, may be promising approaches. We will discuss the composition, function and prognostic value of tumour-infiltrating lymphocytes (TIL) in neuroblastoma, reflect on challenges for immunotherapy, including a lack of TIL reactivity and tumour immune evasion strategies, and highlight opportunities for immunotherapy and future perspectives with regard to state-of-the-art developments in the tumour immunology space.
•TIL in neuroblastoma include T cells, (i)NKT cells, NK cells and few B cells.•TIL infiltration & cytotoxicity associate with survival, risk stage and MYCN status.•Only a small fraction of TIL show anti-tumour reactivity against neuroblastoma.•Neuroblastoma employs many immune evasion strategies hampering immune reactivity.•Combination therapy is an important consideration to overcome immune resistance.
Background
Multidisciplinary cancer team meetings are intended to optimize the diagnosis of a patient with a malignancy. The aim of this study was to assess the number of correct diagnoses formulated ...by the multidisciplinary team (MDT) and whether MDT decisions were implemented.
Methods
In a prospective study, data of consecutive patients discussed at gastrointestinal oncology MDT meetings were studied, and MDT diagnoses were validated with pathology or follow-up. Factors of influence on the correct diagnosis were identified by use of a Poisson regression model. Electronic patient records were used to assess whether MDT decisions were implemented, and reasons to deviate from these decisions were hand-searched within these records.
Results
In 74 MDT meetings, 551 patients were discussed a total of 691 times. The MDTs formulated a correct diagnosis for 515/551 patients (93.4 %), and for 120/551 (21.8 %) patients the MDT changed the referral diagnosis. Of the MDT diagnoses, 451/515 (87.6 %) were validated with pathology. Patients presented to the MDT by their treating physician were 20 % more likely to receive a correct diagnosis relative risk (RR) 1.2, 95 % confidence interval (CI) 1.1–1.5, while the number of patients discussed or the duration of the meeting had no influence on this (RR 1.0, 95 % CI 0.99–1.0; RR 1.0, 95 % CI 0.9–1.1; resp.). MDT decisions were implemented in 94.4 % of cases. Deviations of MDT decisions occurred when a patient’s wishes or physical condition were not taken into account.
Conclusions
MDTs rectify 20 % of the referral diagnoses. The presence of the treating physician is the most important factor to ensure a correct diagnosis and adherence to the treatment plan.
Background Sessile serrated adenomas/polyps (SSAs/Ps) are premalignant lesions susceptible to being easily overlooked by endoscopists. A detailed description of the endoscopic appearance of SSAs/Ps ...might help endoscopists to recognize these lesions to improve the effectiveness of colonoscopy. Objective To identify various endoscopic features of SSAs/Ps using high-resolution white-light endoscopy (HR-WLE) and narrow-band imaging (NBI). Design Retrospective image evaluation study. Setting Single tertiary referral center. Patients Forty-5 patients with serrated polyposis syndrome undergoing surveillance colonoscopies. Intervention HR-WLE and NBI images of 150 polyps (50 SSAs/Ps, 50 hyperplastic polyps HPs, and 50 adenomas) were systematically assessed by 5 experts using various endoscopic descriptors. Main Outcome Measurements The prevalence of specific endoscopic features observed in SSAs/Ps versus HPs. Results Multivariate analysis demonstrated that indistinct borders (OR, 3.11; 95% CI, 1.57-6.15) and a cloud-like surface (OR, 2.65; 95% CI, 1.21-5.78) were associated with SSA/P histology on HR-WLE. On NBI, a cloud-like surface (OR, 4.91; 95% CI, 2.42-9.97), indistinct borders (OR, 2.38; 95% CI, 1.14-4.96), irregular shape (OR, 3.17; 95% CI, 1.59-6.29), and dark spots inside the crypts (OR, 2.05; 95% CI, 1.02-4.11) were found to be endoscopic predictors of SSA/P histology. The sensitivity, specificity, and accuracy of NBI for differentiating serrated polyps containing either none or all 4 endoscopic SSA/P features were, respectively, 89%, 96%, and 93%. Limitations Retrospective, image evaluation analysis. Conclusions The current study demonstrates that SSAs/Ps possess several specific endoscopic features compared with HPs. Recognition of these characteristics might assist endoscopists in the differentiation of these lesions and could possibly facilitate endoscopic detection of these rather subtle lesions.
Background
The clinical course of neuroblastoma stage 4S or MS is characterized by a high rate of spontaneous tumor regression and favorable outcome. However, the clinical course and rate of the ...regression are poorly understood.
Methods
A retrospective cohort study was performed, including all patients with stage 4S neuroblastoma without MYCN amplification, from two Dutch centers between 1972 and 2012. We investigated the clinical characteristics, the biochemical activity reflected in urinary catecholamine excretion, and radiological imaging to describe the kinetics of tumor regression, therapy response and outcome.
Results
The cohort of 31 patients reached a 10‐year overall survival of 84% ± 7% (median follow‐up 16 years; range, 3.3‐39). During the regressive phase, liver size normalized in 91% of the patients and catecholamine excretion in 83%, both after a median of two months (liver size: range, 0‐131; catecholamines: range, 0‐158). The primary tumors completely regressed in 69% after 13 months (range, 6‐73), and the liver architecture normalized in 52% after 15 months (range, 5‐131). Antitumor treatment was given in 52% of the patients. Interestingly, regression rates were similar for treated and untreated patients. Four of seven patients < 4 weeks old died of rapid liver expansion and organ compression. Three patients progressed to stage 4, 3 to 13 months after diagnosis; all had persistently elevated catecholamines.
Conclusion
Patients < 4 weeks old with neuroblastoma stage 4S are at risk of fatal outcome caused by progression of liver metastases. In other patients, tumor regression is characterized by a rapid biochemical normalization that precedes radiological regression.
Neuroblastoma affects mostly young children, bearing a high morbidity and mortality. Liquid biopsies, e.g., molecular analysis of circulating tumor-derived nucleic acids in blood, offer a minimally ...invasive diagnostic modality. Cell-free RNA (cfRNA) is released by all cells, especially cancer. It circulates in blood packed in extracellular vesicles (EV) or attached to proteins. We studied the feasibility of analyzing cfRNA and EV, isolated by size exclusion chromatography (SEC), from platelet-poor plasma from healthy controls (
= 40) and neuroblastoma patients with localized (
= 10) and metastatic disease (
= 30). The mRNA content was determined using several multiplex droplet digital PCR (ddPCR) assays for a neuroblastoma-specific gene panel (
,
,
) and a cell cycle regulation panel (
,
,
,
,
,
). We applied corrections for the presence of platelets. We demonstrated that neuroblastoma-specific markers were present in plasma from 14/30 patients with metastatic disease and not in healthy controls and patients with localized disease. Most cell cycle markers had a higher expression in patients. The mRNA markers were mostly present in the EV-enriched SEC fractions. In conclusion, cfRNA can be isolated from plasma and EV and analyzed using multiplex ddPCR. cfRNA is an interesting novel liquid biopsy-based target to explore further.
Background
Quality indicators (QIs) may be used to monitor the quality of neuroblastoma (NBL) care during treatment, in addition to survival and treatment toxicity, which can only be evaluated in the ...years after treatment. The present study aimed to assess the feasibility of a new set of indicators for the quality of NBL therapy.
Procedure
Seven QIs have been proposed based on literature and consensus of experts: (a) duration of complete diagnostic work‐up, (b) prescription of thyroid prophylaxis before metaiodobenzylguanidine imaging, (c) treatment intensity, (d) use of tumor board meetings, (e) number of outpatient visits and sedation procedures during follow‐up, (f) protocolled follow‐up, and (g) required apheresis sessions. A retrospective data analysis from October 2014 to November 2017 including all patients with NBL in the centralized Princess Máxima Center in the Netherlands was performed to assess these parameters and determine practicality of measurement.
Results
A total number of 72 patients (aged between 2 weeks and 15 years) were analyzed. Adherence to all QIs could be determined for all eligible patients using their electronic medical records. Three indicators were compared over time, and an increase in adherence was observed.
Conclusions
Assessment of QIs in neuroblastoma treatment is feasible. Seven new QIs were found to be feasible to measure and showed improvement over time for three indicators. Monitoring of these QIs during treatment may provide tools for quality improvement activities and comparisons of treatment quality over time or between centers. Further study is required to investigate their association with long‐term outcomes.
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