Albert B. Lowenfels

Risk of pancreatic cancer in patients with cystic fibrosis.

About 5–10% of pancreatic cancers have been linked to an underlying genetic disorder, usually inherited in an autosomal dominant manner. We have previously studied the risk of cancer in patients with cystic fibrosis and found that, although the overall risk of cancer was not increased, there was a fivefold increase in the risk of digestive tract cancer.1,2 Because only four patients developed pancreatic cancer, it was difficult to estimate the risk accurately. Since the publication of these reports we have obtained information on additional patients with both cystic fibrosis and pancreatic cancer from the US cystic fibrosis patient registry, from published reports, and by querying surgeons, pathologists, and cystic fibrosis physicians in the USA, Canada, and Europe.nnWe now describe nine patients with cystic fibrosis and pancreatic cancer identified during the study period (1985 to 2006), including …

Venous thromboembolic events and organ-specific occult cancers: a review and meta-analysis

Summary.u2002 Background:u2002Despite a recognized association between venous thromboembolic events (VTE) and cancer, little is known about the strength and the features of this association. We performed a meta‐analysis in order to clarify this issue. Methods:u2002We retrieved data from 40 reports published between 1982 and 2007: 12 contained cancer risk estimates for patients with either idiopathic or secondary VTE vs. subjects without VTE and 17 for patients with idiopathic vs. secondary VTE. We also pooled risk estimates from four cohort studies to assess the association between VTE and specific forms of cancer and conducted a proportional incidence study, based on the remaining 28 reports, which did not provide risk estimates. Results:u2002The pooled relative risk (RR) of cancer was 3.2 [95% confidence interval (95% CI) 2.4–4.5] for patients with any form of VTE vs. no VTE, 2.7 (95% CI 1.9–3.9) for patients with idiopathic vs. no VTE and 3.8 (95% CI 2.6–5.4) for patients with idiopathic vs. secondary VTE. In the pooled cohort studies, RRs for VTE vs. no VTE were significantly elevated for cancers of the ovary (RR 7.0), pancreas (RR 6.1), liver (RR 5.6), blood (4.2), brain (RR 3.8), kidney (RR 3.4), lung (3.1), colon (2.9), and esophagus (2.1). In the proportional incidence study, cancers of the pancreas, colon, and blood were significantly more frequently observed than in the general population. Conclusions:u2002Overall we found a 3‐fold excess risk of occult cancer in patients with VTE. The risk varies according to tumor site and is highest for cancers of the ovary, pancreas, and liver.

Third International Symposium on Inherited Diseases of the Pancreas

chronic pancreatitis (ICP), the role of this endogenous trypsin inhibitor has been debated. Rolf Graf presented convincing data that SPINK-1 and monitor peptide not only inhibit trypsin in vitro but also participate in a feedback mechanism regulating trypsinogen secretion from pancreatic acinar cells. Both peptides are upregulated and induced as acute phase proteins during infl ammation, cancer development and wound repair. Roger Liddle, Durham, N.C., extended our knowledge on the role of SPINK-1 in pancreatitis by engineering a transgenic mouse model. Using this model he demonstrated that SPINK-1 overexpression in the pancreas ameliorates acute, secretagogue-induced pancreatitis as well as the severity of chronic pancreatitis and long-term fi brosis. Heiko Witt, who fi rst reported on the association between SPINK-1 mutations and idiopathic pancreatitis in 2000, presented a new concept on the role of mutated anionic trypsinogen in the development of pancreatitis. Th e observation that a loss of anionic trypsinogen function mutation protects against pancreatitis emphasized the critical balance between proteases and their inhibitors for the onset of the disease and the necessity to experimentally question the traditional hypothesis. Addressing the genotype/phenotype relationship, John Neoptolemos from Liverpool provided an extensive analysis of the diff erent trypsinogen mutations. Only a minority of the various trypsinogen mutations appear to be of clinical relevance, Th e 5th Symposium on Inherited Diseases of the Pancreas took place immediately aft er the 37th European Pancreatic Club Meeting in Graz, Austria. Th e 1-day meeting was hosted at the Karl Franzens University and was attended by 100 registered participants. Th e aim of the symposium was to bring together not only experts for diseases of the exocrine pancreatic, but also well-known endocrinologists with an interest in the genetics of pancreatic disorders. Th e third group of speakers included molecular and cell biologists with a research focus on pancreatic diseases. 25 invited speakers from 8 diff erent nations contributed to the success of the meeting. A major breakthrough reported at this meeting for the fi rst time was the discovery of the genetic and cell biological changes underlying Johanson-Blizzard syndrome (JBS). Other highlights included progress in unraveling the molecular and cellular mechanisms that underlie the previously reported genetic changes involved in inherited pancreatic disorders. Th e speakers and audience engaged in lively and sometimes controversial discussions, particularly about the pathophysiological and cellular consequences of some of the genetic changes. Th e program began with the ‘Biology and biochemistry of SPINK and monitor peptide’ presented by Rolf Graf from Zurich. Ever since the N34S mutation in the SPINK1 gene was reported to be associated with idiopathic Published online: June 29, 2006

Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations

BACKGROUND & AIMSnImproved therapy has substantially increased survival of persons with cystic fibrosis (CF). But thexa0risk of colorectal cancer (CRC) in adults with CF is 5-10 times greater compared to the general population, and 25-30 times greater in CF patients after an organ transplantation. Toxa0address this risk, the CF Foundation convened a multi-stakeholder task force to develop CRC screening recommendations.nnnMETHODSnThe 18-member task force consisted ofxa0experts including pulmonologists, gastroenterologists, a social worker, nurse coordinator, surgeon, epidemiologist, statistician, CF adult, and a parent. The committee comprised 3xa0workgroups: Cancer Risk, Transplant, and Procedure and Preparation. A guidelines specialist at the CF Foundation conducted an evidence synthesis February-March 2016 based on PubMed literature searches. Task force members conducted additional independent searches. A total of 1159xa0articles were retrieved. After initial screening, the committee read 198 articles in full and analyzed 123 articles to develop recommendation statements. An independent decision analysis evaluating the benefits of screening relative to harms and resources required was conducted by the Department of Public Health at Erasmus Medical Center, Netherlands using the Microsimulation Screening Analysis model from the Cancer Innervation and Surveillance Modelingxa0Network. The task force included recommendation statements in the final guideline only if they reached an 80%xa0acceptance threshold.nnnRESULTSnThe task force makes 10 CRC screening recommendations that emphasize shared, individualized decision-making and familiarity with CF-specific gastrointestinal challenges. We recommend colonoscopy as the preferred screening method, initiation of screening at age 40 years, 5-year re-screening and 3-year surveillance intervals (unlessxa0shorter interval is indicated by individual findings), and a CF-specific intensive bowel preparation. Organ transplant recipients with CF should initiate CRC screening at age 30 years within 2 years of the transplantation because of thexa0additional risk for colon cancer associated with immunosuppression.nnnCONCLUSIONSnThese recommendations aim to help CF adults, families, primary care physicians, gastroenterologists, and CF and transplantation centers address the issue of CRC screening. They differ from guidelines developed for the general population with respect to the recommended age of screening initiation, screening method, preparation, and the interval for repeat screening and surveillance.

Risk of Colorectal Cancer After Solid Organ Transplantation in the United States.

We read with interest the article by Safaeian et al (1), who reported on the risk of colorectal cancer after solid organ transplantation in the United States. They found that recipients undergoing lung transplantation for cystic fibrosis (CF) had greatly increased risk of proximal and distal colon cancer compared with the general population, confirming the results of a US-based cohort study of patients with CF (2).