BACKGROUND-The molecular cause of inflammatory bowel disease is largely unknown.

Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review summarizes the current knowledge of cancer predisposition syndromes in pediatric oncology and provides essential information on clinical situations in which a childhood cancer predisposition syndrome should be suspected.

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Background-Lectins are proteins capable of specific binding to carbohydrates without altering their covalent structure. As an essential part of plants they are ingested in our daily diet. By binding to glycosyl side chains of receptors lectins can mimic or inhibit the action of the ligand. Oral administration of phytohaemagglutinin (PHA) in rats dose dependently induces growth of the small intestine and the pancreas by an unknown mechanism. Aims-To investigate the mechanism of PHA induced intestinal and pancreatic growth. Methods-Thirty day old male rats were pairfed for 10 days with lactalbumin as a control diet or lactalbumin plus PHA or purified soybean trypsin inhibitor (STI) as a positive control (42 mg/rat/day) with or without 20 µg of the cholecystokinin A (CCK-A) antagonist MK 329. To investigate further the eVect of PHA on CCK release intestinal mucosal cells were isolated from rats which were continuously perfused in a perfusion apparatus. CCK release into the medium was assayed. Results-PHA and STI significantly stimulated growth of the pancreas and the small intestine. MK 329 blocked this growth eVect in the pancreas but not in the small intestine. In vivo, PHA significantly increased CCK plasma levels from 0.75 to 6.67 (SEM 2.23) compared with 2.3 (0.35) pM in the control group. In addition, in vitro PHA dose dependently stimulated CCK release with a maximal eVect at 100 ng/ml. Conclusion-In vivo and in vitro PHA is a potent stimulus for CCK release in the rat, thereby inducing pancreatic growth, whereas intestinal growth is stimulated by a CCK independent mechanism.

In a 14-year-old boy with polyposis and rectosigmoid carcinoma, we identified a novel POLE germline mutation, p.(Val411Leu), previously found as recurrent somatic mutation in ‘ultramutated’ sporadic cancers. This is the youngest reported cancer patient with polymerase proofreading-associated polyposis indicating that POLE mutation p.(Val411Leu) may confer a more severe phenotype than previously reported POLE and POLD1 germline mutations. The patient had multiple café-au-lait macules and a pilomatricoma mimicking the clinical phenotype of constitutional mismatch repair deficiency. We hypothesize that these skin features may be common to different types of constitutional DNA repair defects associated with polyposis and early-onset cancer.

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To evaluate the physiological role of cholecystokinin (CCK) in humans, we studied the influence of the specific CCK receptor antagonist loxiglumide (CR 1505) on gallbladder contraction, pancreatic enzyme output, plasma CCK concentrations, mouth-to-cecum transit time (MCTT), stool weight, and fecal fat excretion. Infusion of CCK-8, producing CCK plasma levels of 10-12 pmol/l, decreased gallbladder volume to 21% of the initial volume (P less than 0.01) and increased bilirubin output 8- to 10-fold and pancreatic enzyme secretion 2- to 4-fold. Infusion of loxiglumide (10 mg.kg-1.h-1 iv) abolished CCK-8-stimulated enzyme and bilirubin output. Basal gallbladder volume increased 68% during loxiglumide infusion (P less than 0.001) and 137% (P less than 0.001) after 7 days of oral loxiglumide treatment (3 x 1.6 g/day). Gallbladder contraction and bilirubin output in response to the intraduodenal instillation of a liquid meal (382 kcal) was completely inhibited by loxiglumide; gallbladder volume even increased 45% postprandially during loxiglumide infusion (P less than 0.02) and 145% after long-term loxiglumide treatment (P less than 0.001). Meal-stimulated pancreatic enzyme output was diminished 46-53% after acute and 25-29% after chronic administration of loxiglumide. Meal-stimulated integrated plasma CCK-immunoreactive (CCK-ir) concentrations, determined by RIA, were 3.2-fold higher during loxiglumide infusion (P less than 0.02); plateau CCK levels were markedly elevated (10.1 +/- 1.4 vs. 3.7 +/- 0.5 pM). Plasma CCK-like bioactivity, measured by a sensitive bioassay, was identical to CCK-ir levels in the absence of loxiglumide; in the presence of loxiglumide, no circulating CCK-like bioactivity was detectable, indicating complete inhibition of plasma CCK. MCTT was augmented 24% (P less than 0.05). Oral treatment with loxiglumide increased stool weight 72% (P less than 0.01) and fecal fat excretion 186% (P less than 0.001). In conclusion, 1) meal-induced gallbladder contraction and fasting tone are primarily controlled by CCK; 2) the contribution of CCK to the intestinal phase of postprandial pancreatic enzyme secretion is 40-50%; 3) GI motility and absorption are partially controlled by CCK; and 4) postprandial CCK secretion is substantially augmented by loxiglumide via an unknown mechanism.

DGE after PPPD seems to be of minor clinical importance following uncomplicated surgery. When taking the results into consideration, it can be said that, despite the lack of a control group, antecolic duodenojejunostomy might be the key to a low incidence of DGE after PPPD. In our experience, DGE is linked to the occurrence of other postoperative complications rather than to pylorus preservation.