The global prevalence of cancer is increasing, largely as more patients are living into old age. Therefore, gastroenterologists caring for patients with inflammatory bowel disease [IBD] increasingly are managing patients with cancer, or a previous history of cancer. This often requires joint management with the patient’s oncologist, enabling case-by-case decision-making based on the characteristics and expected evolution of the index cancer. Previously, no European guidelines existed describing the impact of IBD on malignancy. For this reason, the European Crohn’s and Colitis Organisation [ECCO] Guidelines Committee [GuiCom] decided to elaborate a set of Consensus Statements on optimal risk/benefit strategies for treating IBD patients with cancer or a history of cancer. The development of clinical practice guidelines is expensive and time consuming, and it is the Committee’s hope that these statements will facilitate and accelerate future efforts to elaborate formal guidelines, providing useful information on areas for which evidence is lacking and where controlled studies are needed. The strategy used to produce the Consensus Statements involved five steps:

1. Two members of Guicom [VA and RE] identified four main topics that needed to be addressed: a] IBD and solid tumours; b] IBD and skin and haematological malignancies; c] malignancy related to therapy: risk and prevention; and d] management of IBD patients with a history of malignancy. During 2014, calls for participation in the drafting of consensus statements were issued to ECCO members, and selected oncologists known for their expertise and active research in the field were invited to join the Consensus. Participants were selected by the Committee, and four working groups were created, each composed of a chairperson [LE, RE, LB, and VA], two ECCO members including young members [Y-ECCO], and one or two experienced oncologists. The chairmen and their groups elaborated relevant questions on topics dealing with current practice and/or areas …

https://www.spg.pt/wp-content/uploads/2015/11/2015-Inflammatory-Bowel-Disease-and-Malignancies.pdf

European evidence-based consensus: Inflammatory bowel disease and malignancies

PURPOSE: We report the downstaging, sphincter preservation, acute toxicity, and preliminary local control and survival results of preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and concurrent radiation therapy followed by postoperative LV/5-FU for treatment of patients with clinically resectable T3 rectal cancer. MATERIALS AND METHODS: A total of 32 patients received two monthly cycles of preoperative LV/5-FU (bolus daily x 5). Radiation therapy (5,040 cGy) began concurrently on day 1. Postoperatively, patients received a median of two monthly cycles of LV/5-FU (range, 0-10). RESULTS: The complete response rate was 9 percent pathologic and 13 percent clinical, for a total of 22 percent. Total Grade 3+ acute toxicity during the preoperative combined modality segment was 25 percent (8/32). Of the 20 patients who were thought to initially require an abdominoperineal resection and for whom the intent of treatment was sphincter preservation, 17 (85 percent) were able to undergo sphincter-preserving surgery. With a median follow-up of 22 (3-59) months, none have developed local failure, and the three-year actuarial disease-free survival rate was 60 percent. CONCLUSION: Our data reveal encouraging downstaging, sphincter preservation, and acute toxicity with this regimen. Additional follow-up is needed to assess the long-term local control and survival rates.

Preliminary results of preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for clinically resectable T3 rectal cancer

BackgroundChronic rhinosinusitis (CRS) is based on sinonasal symptoms coupled with sinonasal tissue inflammation. Establishing the epidemiology and prevalence of CRS, therefore, is challenging give...

Chronic rhinosinusitis: Epidemiology and burden of disease.

Background. Periodontal disease is a public health problem and is strongly associated with systemic diseases; however, its worldwide distribution is not fully understood. Objective. To evaluate global data of periodontal disease: (1) among adolescents, adults, and older population and (2) in low-, middle-, and high-income countries. Methods. This ecological study included data of periodontal disease from the World Health Organization’s data bank which are based on the Community Periodontal Index of Treatment Needs (CPITN code: 0 = no disease; 1 = bleeding on probing; 2 = calculus; 3 = periodontal pocket (PD) 4-5 mm; 4 = PD (6+ mm). Age- and income-related periodontal disease inequalities were evaluated across the globe. Results. Compared with 9.3% of adults and 9.7% of older persons, 21.2% of adolescents had no periodontal disease ( ). Nearly 18.8% of adolescents compared with 8.9% of adults and 5% of older persons had bleeding on probing ( ). Similarly, 50.3% of adolescents, 44.6% of adults, and 31.9% older persons demonstrated the occurrence of calculus ( ). On the other hand, older persons had the highest prevalence of PD 4-5 mm and PD 6+ mm than adults and adolescents ( ). The distribution of periodontitis (CPITN code 3 + 4) in adults differed significantly in low- (28.7%), lower-middle- (10%), upper-middle- (42.5%), and high-income countries (43.7%) ( ). However, no significant differences in periodontitis (CPITN code 3 + 4) were observed in adolescents and older persons in low- to high-income countries. Conclusions. Within the limitations of data, this study found that the distribution of periodontal disease increases with age. Periodontitis was the most common in older persons and in population from high-income countries.

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Global Prevalence of Periodontal Disease and Lack of Its Surveillance.

Inflammatory bowel disease (IBD)-related colorectal cancer (CRC) is responsible for approximately 2% of the annual mortality from CRC overall, but 10-15% of the annual deaths in IBD patients. IBD-related CRC patients are also affected at a younger age than sporadic CRC patients, and have a 5-year survival rate of 50%. Despite optimal medical treatment, the chronic inflammatory state inherent in IBD increases the risk for high-grade dysplasia and CRC, with additional input from genetic and environmental risk factors and the microbiome. Recognizing risk factors, implementing appropriate surveillance, and identifying high-risk patients are key to managing the CRC risk in IBD patients. Chemoprevention strategies exist, and studies evaluating their efficacy are underway. Once dysplasia or invasive cancer is diagnosed, appropriate surgical resection and postoperative treatment and surveillance are necessary. Here, we discuss the current state of IBD-related CRC, prevalence, risk factors, and evidence for surveillance, prophylaxis, and treatment recommendations.

/pdf/colorectal-cancer-in-inflammatory-bowel-disease-review-of-2lyw083si3.pdf

Colorectal cancer in inflammatory bowel disease: review of the evidence.

Adenocarcinoma, neuroendocrine tumours, sarcomas and lymphomas are the four most common malignant tumours arising in the small intestine, although over forty different histological subtypes are described. Collectively these account for only 2% of cancers of the digestive system. The incidence of small bowel cancer has increased in recent decades with a four-fold increase in carcinoid tumours. Risk factors for small bowel tumours include coeliac disease, inflammatory bowel disease and a number of genetic abnormalities. The non-specific nature of their symptoms and the difficulty in visualising these tumours with normal endoscopic techniques often results in late diagnosis. Furthermore the paucity of literature on this topic has made it difficult to standardise management. There has however been marked improvement in imaging methods resulting in earlier diagnosis in many cases. As expected, early detection of localised, well differentiated tumours followed by surgical resection with negative margins offers the best chance of long term survival. Better adjuvant treatment, notably for gastrointestinal stromal tumours, has improved 5-year survival rates significantly. Development of surveillance guidelines for at risk populations may be a valuable way of improving early diagnosis of this challenging group of conditions.

Malignant tumours of the small intestine.

Background Mucinous differentiation occurs in 5-15 per cent of colorectal adenocarcinomas. This subtype of colorectal cancer responds poorly to chemoradiotherapy and has a worse prognosis. The genetic aetiology underpinning this cancer subtype lacks consensus. The aim of this study was to use meta-analytical techniques to clarify the molecular associations of mucinous colorectal cancer. Methods This study adhered to MOOSE guidelines. Databases were searched for studies comparing KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), p53 and p27 status between patients with mucinous and non-mucinous colorectal adenocarcinoma. A random-effects model was used for analysis. Results Data from 46 studies describing 17 746 patients were included. Mucinous colorectal adenocarcinoma was associated positively with KRAS (odds ratio (OR) 1·46, 95 per cent c.i. 1·08 to 2·00, P = 0·014) and BRAF (OR 3·49, 2·50 to 4·87; P Conclusion The genetic origins of mucinous colorectal adenocarcinoma are predominantly associated with BRAF, MSI and CIMP pathways. This pattern of molecular alterations may in part explain the resistance to standard chemotherapy regimens seen in mucinous adenocarcinoma.

/pdf/meta-analysis-of-the-molecular-associations-of-mucinous-d6fxjwrspq.pdf

Meta-analysis of the molecular associations of mucinous colorectal cancer.

Overexpression of mucin glycoproteins has been demonstrated in many epithelial-derived cancers. The significance of this overexpression remains uncertain. The aim of this paper was to define the association of mucin glycoproteins with apoptosis, cell growth, invasion, migration, adhesion, and clonogenicity in vitro as well as tumor growth, tumorigenicity, and metastasis in vivo in epithelial-derived cancers by performing a systematic review of all published data. A systematic review of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify all papers that evaluated the association between mucin glycoproteins with apoptosis, cell growth, invasion, migration, adhesion, and clonogenicity in vitro as well as tumor growth, tumorigenicity, and metastasis in vivo in epithelial-derived cancers. PRISMA guidelines were adhered to. Results of individual studies were extracted and pooled together based on the organ in which the cancer was derived from. The initial search revealed 2031 papers, of which 90 were deemed eligible for inclusion in the study. The studies included details on MUC1, MUC2, MUC4, MUC5AC, MUC5B, MUC13, and MUC16. The majority of studies evaluated MUC1. MUC1 overexpression was consistently associated with resistance to apoptosis and resistance to chemotherapy. There was also evidence that overexpression of MUC2, MUC4, MUC5AC, MUC5B, MUC13, and MUC16 conferred resistance to apoptosis in epithelial-derived cancers. The overexpression of mucin glycoproteins is associated with resistance to apoptosis in numerous epithelial cancers. They cause resistance through diverse signaling pathways. Targeting the expression of mucin glycoproteins represents a potential therapeutic target in the treatment of epithelial-derived cancers.

/pdf/mucin-glycoproteins-block-apoptosis-promote-invasion-4xz17bgaiv.pdf

Mucin glycoproteins block apoptosis; promote invasion, proliferation, and migration; and cause chemoresistance through diverse pathways in epithelial cancers

Aim
Anastomotic leak (AL) after anterior resection results in increased morbidity, mortality and local recurrence. The aim of this study was to assess the ability of C-reactive protein (CRP) to predict AL in the first week after anterior resection for rectal cancer.

Method
A retrospective review of a prospectively maintained database that included all patients undergoing anterior resection between January 2008 and December 2013 was performed. The ability of CRP to predict AL was assessed using area under the receiver–operating characteristics (AUC) curves. The severity of AL was defined using the International Study Group of Rectal Cancer (ISREC) grading system.

Results
Two-hundred and eleven patients were included in the study. Statistically significant differences in mean CRP values were found between those with and without an AL on postoperative days 5, 6 and 7. A CRP value of 132 mg/l on postoperative day 5 had an AUC of 0.75, corresponding to a sensitivity of 70%, a specificity of 76.6%, a positive predictive value of 16.3% and a negative predictive value of 97.5%. Multivariable analysis found that a CRP of > 132 mg/l on postoperative day 5 was the only statistically significant patient factor that was linked to an increased risk of AL (HR = 8.023, 95% CI: 1.936–33.238, P = 0.004).

Conclusion
Early detection of AL may minimize postoperative complications. CRP is a useful negative predictive test for the development of AL following anterior resection.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/codi.13649

C-reactive protein as a predictor of anastomotic leak in the first week after anterior resection for rectal cancer.

Data sourcesMedline, Embase, OpenGrey, Journal of Clinical Periodontology, Journal of Periodontology and a hand search of the bibliographies of retrieved publications.Study selectionTwo reviewers screened the title and abstract of 1134 studies from the literature and selected 37 suitable publications for inclusion following full text analysis of 109 papers and agreement between both reviewers. The search included observational, epidemiological studies and clinical trials that fufilled the inclusion criteria. The publications assessed contained a periodontal clinical examination and a validated OHRQoL questionnaire. There were no language restrictions and the review was performed according to the MOOSE statement.Data extraction and synthesisData were extracted from each study applying the PECO format. The quality of the observational studies was evaluated by the Newcastle Ottawa Scale (NOS) and clinical trials by the (MINORS) methodological index for non-randomised studies. The Strength of Grading Taxonomy (SORT) was utilised to assess the level of evidence and strength of recommendation of the included studies. A meta-analysis was not undertaken due the heterogeneity of the included studies, therefore results were synthesised by applying a vote counting method.ResultsThirty-seven studies included in the review were evaluated by the vote counting method. According to NOS and MINORS the risk of bias was identified as moderate with most studies assessing 50% to 83% of the parameters established. A level two for quality of evidence and a level B for strength of recommendation were applicable for the relationship between clinically diagnosed periodontal disease and OHRQoL. The evidence level was consistent across the studies. Nineteen of the studies examined a distinct population group with respect to diagnosis of systemic disease, socioeconomic status, demographic background or periodontal diagnosis. Twenty-eight of the included studies reported an association between periodontal diseases and OHRQoL while eight of the publications highlighted a dose-response relationship between and extent and severity of periodontal disease and the impact on OHRQoL.ConclusionsThe findings support the association between clinically diagnosed periodontal diseases and subjectively assessed OHRQoL with a dose-response relationship demonstrated. In summation, periodontal diseases play a significant role in oral health and impact on the QoL of affected individuals. In publications that undertook a full mouth recording the results were more evident, therefore a comprehensive periodontal exam in conjunction with a validated OHRQoL questionnaire is recommended.

Ian S Reynolds

Papers

Malignant tumours of the small intestine.

Meta-analysis of the molecular associations of mucinous colorectal cancer.

Mucin glycoproteins block apoptosis; promote invasion, proliferation, and migration; and cause chemoresistance through diverse pathways in epithelial cancers

C-reactive protein as a predictor of anastomotic leak in the first week after anterior resection for rectal cancer.

Periodontal disease has an impact on patients' quality of life.