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Inflammation is a recognised hallmark of cancer that substantially contributes to the development and progression of malignancies. In established cancers, there is increasing evidence for the roles that local immune response and systemic inflammation have in progression of tumours and survival of patients with cancer. This knowledge provides an opportunity to target these inflammatory responses to improve patient outcomes. In this Review, we examine the complex interplay between local immune responses and systemic inflammation, and their influence on clinical outcomes, and propose potential anti-inflammatory interventions for patients with cancer.

Lynch syndrome is one of the most common hereditary cancer predisposition syndromes and is associated with increased risks of colorectal and endometrial cancer, as well as multiple other cancer types. While the mechanism of mismatch repair deficiency and microsatellite instability and its role in Lynch-associated carcinogenesis has been known for some time, there have been significant advances recently in diagnostic testing and the understanding of the molecular pathogenesis of Lynch tumors. There is also an increased awareness that the clinical phenotype and cancer risk varies by specific mismatch repair mutation, which in turn has implications on surveillance strategies for patients. Even the treatment of Lynch-associated cancers has changed with the addition of immunotherapy for advanced disease. This progress report aims to review some of the many advances in epidemiology, molecular pathogenesis, diagnosis, clinical phenotype, cancer surveillance, treatment, and chemo- and immune-prevention strategies in the Lynch syndrome field over the past 5 years.

Key Points The nature of a given active surveillance (AS) protocol is dependent on the three core components of AS: criteria for selection, monitoring strategy, and triggers for intervention Among large AS programmes, selection criteria range from very-low-risk to intermediate-risk disease, and monitoring protocols vary widely in frequency of prostate biopsy; histological upgrading is a trigger for intervention in most programmes In AS cohorts with at least 5 years of available follow-up data, treatment was pursued in 24–40% of men; metastatic disease occurred in 0.1–2.8%, and prostate-cancer-specific death in 0–1.5% Intermediate-term outcomes are dependent on programme-specific criteria; intensive programmes (close monitoring, low intervention thresholds) are associated with high rates of treatment and low rates of adverse oncological outcomes In the absence of a single optimal AS protocol, individualizing AS intensiveness to each man's risks and expectations is a reasonable approach, only once he has been counselled on the existing data and its known limitations Accurate measurement and reporting of time-dependent data are critical in order to establish reliable benchmarks for counselling and pave the way toward identifying an optimized approach Active surveillance as a management strategy for favourable-risk prostate cancer has increased in recent years, in an effort to prevent the adverse effects associated with unnecessary overtreatment of low-risk disease. However, long-term data have, in the past, been lacking, making it difficult to assess the effectiveness of this approach. In this Review, Tosoian et al . discuss the current state-of-the-art in active surveillance, reviewing the available evidence and considering future directions in the field. Prostate cancer remains one of the most commonly diagnosed malignancies worldwide. Early diagnosis and curative treatment seem to improve survival in men with unfavourable-risk cancers, but significant concerns exist regarding the overdiagnosis and overtreatment of men with lower-risk cancers. To this end, active surveillance (AS) has emerged as a primary management strategy in men with favourable-risk disease, and contemporary data suggest that use of AS has increased worldwide. Although published surveillance cohorts differ by protocol, reported rates of metastatic disease and prostate-cancer-specific mortality are exceedingly low in the intermediate term (5–10 years). Such outcomes seem to be closely associated with programme-specific criteria for selection, monitoring, and intervention, suggesting that AS — like other management strategies — could be individualized based on the level of risk acceptable to patients in light of their personal preferences. Additional data are needed to better establish the risks associated with AS and to identify patient-specific characteristics that could modify prognosis.

Prostate cancer is a major public health problem with considerable uncertainties about the effectiveness of population screening and treatment options. We report the study design, participant sociodemographic and clinical characteristics, and the initial results of the testing and diagnostic phase of the Prostate testing for cancer and Treatment (ProtecT) trial, which aims to investigate the effectiveness of treatments for localised prostate cancer. In this randomised phase 3 trial, men aged 50–69 years registered at 337 primary care centres in nine UK cities were invited to attend a specialist nurse appointment for a serum prostate-specific antigen (PSA) test. Prostate biopsies were offered to men with a PSA concentration of 3·0 μg/L or higher. Consenting participants with clinically localised prostate cancer were randomly assigned to active monitoring (surveillance strategy), radical prostatectomy, or three-dimensional conformal external-beam radiotherapy by a computer-generated allocation system. Randomisation was stratified by site (minimised for differences in participant age, PSA results, and Gleason score). The primary endpoint is prostate cancer mortality at a median 10-year follow-up, ascertained by an independent committee, which will be analysed by intention to treat in 2016. This trial is registered with ClinicalTrials.gov, number NCT02044172, and as an International Standard Randomised Controlled Trial, number ISRCTN20141297. Between Oct 1, 2001, and Jan 20, 2009, 228 966 men were invited to attend an appointment with a specialist nurse. Of the invited men, 100 444 (44%) attended their initial appointment and 82 429 (82%) of attenders had a PSA test. PSA concentration was below the biopsy threshold in 73 538 (89%) men. Of the 8566 men with a PSA concentration of 3·0–19·9 μg/L, 7414 (87%) underwent biopsies. 2896 men were diagnosed with prostate cancer (4% of tested men and 39% of those who had a biopsy), of whom 2417 (83%) had clinically localised disease (mostly T1c, Gleason score 6). With the addition of 247 pilot study participants recruited between 1999 and 2001, 2664 men were eligible for the treatment trial and 1643 (62%) agreed to be randomly assigned (545 to active monitoring, 545 to radiotherapy, and 553 to radical prostatectomy). Clinical and sociodemographic characteristics of randomly assigned participants were balanced across treatment groups. The ProtecT trial randomly assigned 1643 men with localised prostate cancer to active monitoring, radiotherapy, or surgery. Participant clinicopathological features are more consistent with contemporary patient characteristics than in previous prostate cancer treatment trials. UK National Institute for Health Research Health Technology Assessment Programme.

Research into magnetic resonance imaging (MRI) for prostate cancer screening and diagnosis has been ongoing for more than a decade. Initially, MRI was thought to be important for achieving two goals. Among patients with low-grade (International Society of Urological Pathology [ISUP] grade 1, also called Gleason grade group 1) disease diagnosed on the basis of systematic biopsy, there was some hesitation to undergo active surveillance because of the possibility of missed higher-grade disease. An absence of high-grade lesions on MRI could help to allay those concerns. 1,2 In addition, systematic biopsy could miss high-grade disease when it is actually present and . . .

Active surveillance (AS) has been widely adopted as an alternative to immediate surgery owing to the indolent nature and favorable outcomes of papillary thyroid microcarcinoma (PTMC). AS is generally recommended for tumors measuring ≤1 cm without aggressive cytological subtypes, risk of gross extrathyroidal extension (ETE), lymph node metastasis (LNM), or distant metastasis. AS requires careful patient selection based on various patient and tumor characteristics, and ultrasound (US) findings. Moreover, during AS, regular US is performed to monitor any signs of tumor progression, including tumor growth, new US features of potential gross ETE, and LNM. Therefore, appropriate imaging-based assessment plays a crucial role in determining whether AS or surgery should be pursued. However, detailed recommendations concerning US evaluation are currently insufficient, necessitating the formulation of this guideline. The Korean Society of Thyroid Radiology has developed a consensus statement for low-risk PTMC, covering US assessment methods when considering AS as a management option and conducting follow-up imaging tests during AS. This guideline aims to provide optimal scientific evidence and expert opinion consensus regarding a standardized US-based assessment protocol for low-risk PTMC.

Barrett's esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.

Abstract Context Active surveillance (AS) of thyroid cancer with serial ultrasounds is a newer management option in the United States. Objective This work aimed to understand factors associated with the adoption of AS. Methods We surveyed endocrinologists and surgeons in the American Medical Association Masterfile. To estimate adoption, respondents recommended treatment for 2 hypothetical cases appropriate for AS. Established models of guideline implementation guided questionnaire development. Outcome measures included adoption of AS (nonadopters vs adopters, who respectively did not recommend or recommended AS at least once; and partial vs full adopters, who respectively recommended AS for one or both cases). Results The 464 respondents (33.3% response) demographically represented specialties that treat thyroid cancer. Nonadopters (45.7%) were significantly (P < .001) less likely than adopters to practice in academic settings, see more than 25 thyroid cancer patients/year, be aware of AS, use applicable guidelines (P = .04), know how to determine whether a patient is appropriate for AS, have resources to perform AS, or be motivated to use AS. Nonadopters were also significantly more likely to be anxious or have reservations about AS, be concerned about poor outcomes, or believe AS places a psychological burden on patients. Among adopters, partial and full adopters were similar except partial adopters were less likely to discuss AS with patients (P = .03) and more likely to be anxious (P = .04), have reservations (P = .03), and have concerns about the psychological burden (P = .009) of AS. Few respondents (3.2%) believed patients were aware of AS. Conclusion Widespread adoption of AS will require increased patient and physician awareness, interest, and evaluation of outcomes.

Septoplasty (surgical correction of the deviated nasal septum) is the most frequently performed ear, nose, and throat operation in adults, but no randomised controlled trials or non-randomised comparative studies on the effectiveness of septoplasty have been published. Consequently, health-care providers, health insurance companies, and policy makers are concerned about the effectiveness of the procedure. We aimed to assess the effectiveness of septoplasty for nasal obstruction in adults with a deviated septum. We did this open, multicentre, pragmatic, randomised controlled trial in 16 secondary and two tertiary referral hospitals in the Netherlands. Adults (aged ≥18 years) with nasal obstruction, a deviated septum, and an indication to have septoplasty done were randomly allocated (1:1) to receive either septoplasty with or without concurrent turbinate surgery or non-surgical management. Patients were stratified by sex, age (<35 years or ≥35 years), and deviation severity (mild, moderate, or severe). The primary outcome was health-related quality of life, measured with the validated Glasgow Health Status Inventory at 12 months. Analyses were done on an intention-to-treat basis. The trial is registered with the Netherlands Trial Register, number NTR3868. Between Sept 2, 2013, and Dec 12, 2016, we randomly assigned 203 participants to receive either septoplasty with or without concurrent turbinate surgery (n=102) or non-surgical management (n=101). 189 participants were analysed at 12 months. At 12 months, mean score on the Glasgow Health Status Inventory of patients assigned to septoplasty was 72·2 (SD 12·2) and for those assigned to non-surgical management was 63·9 (SD 14·5, mean difference 8·3 [95% CI 4·5–12·1], favouring septoplasty). Septal abscess occurred in one surgical patient and septal perforation in two surgical patients. No side-effects of nasal medication were reported. Septoplasty is more effective than non-surgical management for nasal obstruction in adults with a deviated septum. This effect was sustained up to 24 months of follow-up. The Netherlands Organisation for Health Research and Development (ZonMw).

Objective To review the components of past and present active surveillance (AS) protocols, provide an overview of the current studies employing artificial intelligence (AI) in AS of prostate cancer, discuss the current challenges of AI in AS, and offer recommendations for future research. Methods Research studies on the topic of MRI-based AI were reviewed to summarize current possibilities and diagnostic accuracies for AI methods in the context of AS. Established guidelines were used to identify possibilities for future refinement using AI. Results Preliminary results show the role of AI in a range of diagnostic tasks in AS populations, including the localization, follow-up, and prognostication of prostate cancer. Current evidence is insufficient to support a shift to AI-based AS, with studies being limited by small dataset sizes, heterogeneous inclusion and outcome definitions, or lacking appropriate benchmarks. Conclusion The AI-based integration of prostate MRI is a direction that promises substantial benefits for AS in the future, but evidence is currently insufficient to support implementation. Studies with standardized inclusion criteria and standardized progression definitions are needed to support this. The increasing inclusion of patients in AS protocols and the incorporation of MRI as a scheduled examination in AS protocols may help to alleviate these challenges in future studies. Clinical relevance statement This manuscript provides an overview of available evidence for the integration of prostate MRI and AI in active surveillance, addressing its potential for clinical optimizations in the context of established guidelines, while highlighting the main challenges for implementation. Key Points Active surveillance is currently based on diagnostic tests such as PSA, biopsy, and imaging . Prostate MRI and AI demonstrate promising diagnostic accuracy across a variety of tasks, including the localization, follow-up and risk estimation in active surveillance cohorts . A transition to AI-based active surveillance is not currently realistic; larger studies using standardized inclusion criteria and outcomes are necessary to improve and validate existing evidence .