The Delphi and GRADE methodology used in the PSOGI 2018 consensus statement on Pseudomyxoma Peritonei and Peritoneal Mesothelioma

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%–100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future

Worldwide Esophageal Cancer Collaboration : clinical staging data

Peer reviewe

A Validation of the Swedish Colorectal Cancer Register – With Focus on Histopathology, Complications and Recurrences

Örvar Arnarson,1,* Peter Moberger,2,3,* Filip Sköldberg,4,5 Kenneth Smedh,2,3 Helgi Birgisson,4,5 Ingvar Syk1 1Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden; 2Centre for Clinical research Västerås, Uppsala University, Uppsala, Sweden; 3Department of Surgery Västmanlands Hospital Västerås, Västerås, Sweden; 4Gastrointestinal Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; 5Department of Surgery, Uppsala University Hospital, Uppsala, Sweden*These authors contributed equally to this workCorrespondence: Ingvar Syk, Department of Surgery, Skåne University Hospital, Malmö, SE-214 28, Email [email protected]: There is an urgent need to evaluate the quality of healthcare systems to improve and deliver high-quality care. Clinical registries have become important platforms for performance measurements, improvements, and clinical research. Hence, the quality of data in registries is crucial. This study aimed to assess the validity of data in the Swedish Colorectal Cancer Register (SCRCR).Methods: Seven hundred patients from 12 hospitals were randomly selected and proportionally distributed among three different hospital categories in Sweden using two-stage cluster sampling. Validity was assessed by re-abstracting data from the medical files of patients reported to the SCRCR in 2015. Data on histopathology, postoperative complications, and a 3-year follow-up were selected for validation. Re-abstracted data were defined as source data, and validity was defined as the proportion of cases in the SRCRC dataset that agreed with the source data. Validity was expressed as the percentage of exact agreement of non-missing data in both data sets, and Cohen´s kappa coefficient (κ) was used to measure the strength of the agreement.Results: The median agreement of the categorical histopathology variables was 93.4% (κ = 0.83). The general postoperative complication variable showed substantial agreement (84.3%, κ = 0.61). Likewise, the variable for overall cancer recurrence showed an almost perfect agreement (95.7%, κ = 0.86), whereas specific variables for local recurrence and distant recurrence displayed only moderate and fair agreement (85.9% and 89.1%, κ = 0.58 and 0.34, respectively).Conclusion: Validation of the SCRCR data showed high validity of pathology data and recurrence rates, whereas detailed data on recurrence were not as good. Data on postoperative complications were less reliable, although the incidence and Clavien–Dindo grading of severe complications (grade 3b or higher) were reliable.Keywords: quality registry, national registry, validation, colorectal cancer, Swedish registr

Esophagectomy without mortality: What can surgeons do?

Introduction: Surgical resection remains the mainstay treatment for patients with localized esophageal cancer. It is, however, a complex procedure. Mortality rate used to be high, but in recent years, death rate has been reduced to below 5% in specialized centers. Methods: Outcome of esophagectomy can be improved by paying attention to (1) appropriate patient section, (2) choice of surgical techniques and their execution, and (3) optimizing perioperative care. A volume-outcome relationship is also evident. Surgeons can perform esophagectomy without mortality, but a multi-disciplinary team management is essential to achieve this goal. © 2009 The Society for Surgery of the Alimentary Tract.postprin

A phase 1 trial of the safety, tolerability and biological effects of intravenous Enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR)

Background: Chemoradiotherapy remains the standard of care for locally advanced rectal cancer. Efforts to intensify treatment and increase response rates have yet to yield practice changing results due to increased toxicity and/or absence of increased radiosensitization. Enadenotucirev (EnAd) is a tumour selective, oncolytic adenovirus which can be given intravenously. Pre-clinical evidence of synergy with radiation warrants further clinical testing and assessment of safety with radiation. Methods: Eligibility include histology confirmed locally advanced rectal cancer that require chemoradiation. The trial will use a Time-to-Event Continual Reassessment Model-based (TiTE-CRM) approach using toxicity and efficacy as co-primary endpoints to recommend the optimal dose and treatment schedule 30 patients will be recruited. Secondary endpoints include pathological complete response the neoadjuvant rectal score. A translational program will be based on a mandatory biopsy during the second week of treatment for ‘proof-of-concept’ and exploration of mechanism. The trial opened to recruitment in July 2019, at an expected rate of 1 per month for up to 4 years. Discussion: Chemoradiation with Enadenotucirev as a radiosensitiser in locally Advanced Rectal cancer (CEDAR) is a prospective multicentre study testing a new paradigm in radiosensitization in rectal cancer. The unique ability of EnAd to selectively infect tumour cells following intravenous delivery is an exciting opportunity with a clear translational goal. The novel statistical design will make efficient use of both toxicity and efficacy data to inform subsequent studies. Trial registration: ClinicalTrial.gov, NCT03916510. Registered 16th April 2019

IgE sensitisation in relation to flow-independent nitric oxide exchange parameters

BACKGROUND: A positive association between IgE sensitisation and exhaled NO levels has been found in several studies, but there are no reports on the compartment of the lung that is responsible for the increase in exhaled NO levels seen in IgE-sensitised subjects. METHODS: The present study comprised 288 adult subjects from the European Community Respiratory Health Survey II who were investigated in terms of lung function, IgE sensitisation (sum of specific IgE), smoking history and presence of rhinitis and asthma. Mean airway tissue concentration of NO (Caw(NO)), airway transfer factor for NO (Daw(NO)), mean alveolar concentration of NO (Calv(NO)) and fractional exhaled concentration of NO at a flow rate of 50 mL s(-1 )(FE(NO 0.05)) were determined using the extended NO analysis. RESULTS: IgE-sensitised subjects had higher levels (geometric mean) of FE(NO 0.05 )(24.9 vs. 17.3 ppb) (p < 0.001), Daw(NO )(10.5 vs. 8 mL s(-1)) (p = 0.02) and Caw(NO )(124 vs. 107 ppb) (p < 0.001) and positive correlations were found between the sum of specific IgE and FE(NO 0.05), Caw(NO )and Daw(NO )levels (p < 0.001 for all correlations). Sensitisation to cat allergen was the major determinant of exhaled NO when adjusting for type of sensitisation. Rhinitis and asthma were not associated with the increase in exhaled NO variables after adjusting for the degree of IgE sensitisation. CONCLUSION: The presence of IgE sensitisation and the degree of allergic sensitisation were related to the increase in airway NO transfer factor and the increase in NO concentration in the airway wall. Sensitisation to cat allergen was related to the highest increases in exhaled NO parameters. Our data suggest that exhaled NO is more a specific marker of allergic inflammation than a marker of asthma or rhinitis

Metalloproteinases and their inhibitors—diagnostic and therapeutic opportunities in orthopedics

Matrix metalloproteinases (MMPs) and related enzymes (ADAMs, ADAMTS) and their inhibitors control matrix turnover and function. Recent advances in our understanding of musculoskeletal conditions such as tendinopathy, arthritis, Dupuytren's disease, degenerative disc disease, and bone and soft tissue healing suggest that MMPs have prominant roles. Importantly, MMPs are amenable to inhibition by cheap, safe, and widely available drugs such as the tetracycline antibiotics and the bisphosphonates. This indicates that these MMP inhibitors, if proven effective for any novel indication, may be quickly brought into clinical practice

Magnetic resonance imaging (MRI) in rectal cancer: a comprehensive review

Magnetic resonance imaging (MRI) has established itself as the primary method for local staging in patients with rectal cancer. This is due to several factors, most importantly because of the ability to assess the status of circumferential resection margin. There are several newer developments being introduced continuously, such as diffusion-weighted imaging and imaging with 3 T. Assessment of loco-regional lymph nodes has also been investigated extensively using different approaches, but more work needs to be done. Finally, evaluation of tumours during or after preoperative treatment is becoming an everyday reality. All these new aspects prompt a review of the most recent advances and opinions. In this review, a comprehensive overview of the current status of MRI in the loco-regional assessment and management of rectal cancer is presented. The findings on MRI and their accuracy are reviewed based on the most up-to-date evidence. Optimisation of MRI acquisition and relevant regional anatomy are also presented, based on published literature and our own experience

Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection:an international, multi-centre, prospective audit

Introduction: The optimal bowel preparation strategy to minimise the risk of anastomotic leak is yet to be determined. This study aimed to determine whether oral antibiotics combined with mechanical bowel preparation (MBP+Abx) was associated with a reduced risk of anastomotic leak when compared to mechanical bowel preparation alone (MBP) or no bowel preparation (NBP). Methods: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 Left Sided Colorectal Resection audit was performed. Patients undergoing elective left sided colonic or rectal resection with primary anastomosis between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak. Results: Of 3676 patients across 343 centres in 47 countries, 618 (16.8%) received MBP+ABx, 1945 MBP (52.9%) and 1099 patients NBP (29.9%). Patients undergoing MBP+ABx had the lowest overall rate of anastomotic leak (6.1%, 9.2%, 8.7% respectively) in unadjusted analysis. After case-mix adjustment using a mixed-effects multivariable regression model, MBP+Abx was associated with a lower risk of anastomotic leak (OR 0.52, 0.30–0.92, P&nbsp;=&nbsp;0.02) but MBP was not (OR 0.92, 0.63–1.36, P&nbsp;=&nbsp;0.69) compared to NBP. Conclusion: This non-randomised study adds ‘real-world’, contemporaneous, and prospective evidence of the beneficial effects of combined mechanical bowel preparation and oral antibiotics in the prevention of anastomotic leak following left sided colorectal resection across diverse settings. We have also demonstrated limited uptake of this strategy in current international colorectal practice