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Background: This is an analysis of the first 50 in-human uses of a novel digital rigid sigmoidoscope. The technology provides digital image capture, telemedicine capabilities, improved ergonomics, and the ability to biopsy under pneumorectum while maintaining the low cost of conventional rigid sigmoidoscopy. The primary outcome was adverse events, and the secondary outcome was diagnostic view., Preliminary Results: Fifty patients underwent outpatient (n = 25) and surgical rectal assessment (n = 25), with a mean age of 60 years. This included 31 men and 19 women with 12 different clinical use indications. No adverse events were reported, and no defects were reported with the instrumentation. Satisfactory diagnoses were obtained in 48 (96%) of 50 uses, images were captured in 48 (96%) of 50 uses, and biopsies were successfully taken in 13 uses (26%). No adverse events were recorded. Independent reviewers of recorded videos agreed on the quality and diagnostic value of the images with a κ of 0.225 (95% CI, 0.144-0.305) when assessing whether the target pathology was adequately visualized., Impact of Innovation: The improved views afforded by digital rectoscopy facilitated a satisfactory clinical diagnosis in 96% of uses. The device was successfully deployed in the operating room and outpatients irrespective of bowel preparation method, where it has the potential to replace flexible sigmoidoscopy for specific use cases. The technology provides a high-quality image and video that can be securely recorded for documentation and medicolegal purposes with agreement between blinded users despite a lack of standardized training and heterogenous pathology. We perceive significant impact of this technology for the assessment of colorectal anastomoses, the office management of colitis, "watch and wait," and for diagnostic support in rectal cancer diagnosis. The technology has significant potential to facilitate proctoring and training, and it now requires prospective trials to validate its diagnostic accuracy against more costly flexible sigmoidoscopy systems., (Copyright © The ASCRS 2021.)

Objective: To characterise the phenotypes associated with the p.A16V mutation of PRSS1., Design: Clinical and epidemiological data were collected for any family in which a p.A16V mutation was identified, either referred directly to the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer or via a collaborator. DNA samples were tested for mutations in PRSS1, SPINK1, CFTR and CTRC., Patients: Participants were recruited on the basis of either family history of pancreatitis (acute or chronic) or the results of genetic testing. Families were categorised as having hereditary pancreatitis (HP), idiopathic disease or pancreatitis in a single generation. HP was defined as >or=2 cases in >or=2 generations. Main outcome measures Onset of painful episodes of pancreatitis, death from pancreatic cancer, diagnosis of diabetes mellitus and exocrine pancreatic failure., Results: Ten families with p.A16V mutations were identified (22 affected individuals): six HP families, three with idiopathic disease and one with only a single generation affected. The median age of onset, ignoring non-penetrants, was 10 years (95% CI 5 to 25). There were eight confirmed cases of exocrine failure, four of whom also had diabetes mellitus. There were three pancreatic cancer cases. Two of these were confirmed as p.A16V carriers, only one of whom was affected by pancreatitis. Those with p.A16V pancreatitis were compared to affected individuals with p.R122H, p.N29I and no PRSS1 mutation. No significant differences were proven using logrank or Mann-Whitney U tests., Conclusions: Penetrance of p.A16V is highly variable and family dependent, suggesting it contributes to multigenic inheritance of a predisposition to pancreatitis.

Familial Pancreatic Cancer (FPC) is the autosomal dominant inheritance of a genetic predisposition to pancreatic ductal adenocarcinoma, penetrance is assumed to be high but not complete. It was first described in 1987 and since then many families have been identified, but the candidate disease gene remains elusive and the very existence of the syndrome is sometimes questioned. FPC identifies a target group for secondary screening. As well as being potentially life saving for the subjects, screening offers researchers the opportunity to elucidate the early pathogenesis of pancreatic cancer. The scientific incentive for screening should not blind us to the challenges facing clinicians in managing high risk patients. Early surgical treatment may dramatically improve the five year survival for pancreatic cancer, but this must be balanced against the risks of false positives, where healthy individuals are subjected to the mortality and morbidity of major pancreatic surgery.

Background: Cancer risk, including pancreatic, is high in those with Peutz-Jeghers syndrome (PJS). It has been suggested that such patients should undergo screening for pancreatic cancer., Methods: The risk of pancreatic cancer in PJS, pancreatic screening and potential screening strategies were reviewed. Cost-effectiveness was assessed according to American Gastroenterology Association guidelines and a risk stratification model proposed by the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer., Results: The risk of pancreatic cancer is increased in PJS but screening would cost over US 35,000 dollars per life saved. Risk stratification reduces cost by 100,000 dollars and costs fall to 50,000 dollars per life saved if deaths from other forms of cancer are avoided., Conclusion: Screening should be performed only on a research basis to evaluate the benefit and cost-effectiveness in high-risk groups.

Background: Familial pancreatic cancer (FPC) describes a group of families where the inheritance of pancreatic cancer is consistent with an autosomal-dominant mode of inheritance. The 4q32-34 region has been previously identified as a potential locus for FPC in a large American family., Methods: The region was allelotyped in 231 individuals from 77 European families using nine microsatellite markers, and haplotyping was possible in 191 individuals from 41 families. Families were selected based on at least two affected first-degree relatives with no other cancer syndromes., Results: Linkage to most of the locus was excluded based on LOD scores less than -2.0. Eight families were excluded from linkage to 4q32-34 based on haplotypes not segregating with the disease compared with a predicted six to seven families. Two groups of families were identified, which seem to share common alleles within the minimal disease-associated region of 4q32-34, one group with an apparently earlier age of cancer death than the other pancreatic cancer families. Four genes were identified with potential tumor suppressor roles within the locus in regions that could not be excluded based on the LOD score. These were HMGB2, PPID, MORF4, and SPOCK3. DNA sequence analysis of exons of these genes in affected individuals and in pancreatic cancer cell lines did not reveal any mutations., Conclusion: This locus is unlikely to harbor a FPC gene in the majority of our European families.

There are multiple PRSS1 mutations described in hereditary pancreatitis but only a minority of these are clinically relevant. The two most frequent point mutations are in exon 2 (N29I) and exon3 (R122H), found in diverse racial populations. Both mutations result in early onset pancreatitis but the mechanism underlying this phenotype is unclear. The frequency of these mutations in such diverse populations suggests they have spontaneously occurred many times. The origin of the major mutations may be explained by gene conversions, accounting for multiple founders. The implications are discussed in terms of mechanism of action of the mutations and clinical presentation.

It is estimated that pancreatic cancer has a familial component in approximately 5-10% of cases. Some of these cases are part of a defined cancer syndrome with a known gene mutation but in the remaining the causative gene remains unknown. In recent years, a better understanding of the molecular events that occur in the progression model of pancreatic cancer has lead to the development of secondary screening programmes with the aim of identifying early precursor lesions or pre-invasive cancer at a stage amenable to curative resection. High-risk groups who have an inherited predisposition for pancreatic cancer form the ideal group to study in developing a robust screening programme. Multimodality screening using computed tomography and endoluminal ultrasound in combination with molecular analysis of pancreatic juice are proving promising as diagnostics tools or at least serving as predictors of risk over a defined period.

Hereditary pancreatitis is an autosomal dominant disease with incomplete penetrance (80%), accounting for approximately 1% of all cases of pancreatitis. It is characterized by the onset of recurrent attacks of acute pancreatitis in childhood and frequent progression to chronic pancreatitis. Whitcomb et al. identified the cationic trypsinogen gene (PRSS1) on chromosome 7q35 as the site of the mutation that causes hereditary pancreatitis. The European registry of hereditary pancreatitis and familial pancreatic cancer (EUROPAC) aims to identify and make provisions for those affected by hereditary pancreatitis and familial pancreatic cancer. The most common mutations in hereditary pancreatitis are R122H, N29I and A16V but many families have been described with clinically defined hereditary pancreatitis where there is no PRSS1 mutation. It is known that the cumulative lifetime risk (to age 70 years) of pancreatic cancer is 40% in individuals with hereditary pancreatitis. This subset of individuals form an ideal group for the development of a screening programme aimed at detecting pancreatic cancer at an early stage in an attempt to improve the presently poor long-term survival. Current screening strategies involve multimodality imaging (computed tomography, endoluminal ultrasound) and endoscopic retrograde cholangiopancreatography for pancreatic juice collection followed by molecular analysis of the DNA extracted from the juice. The potential benefit of screening (curative resection) must be balanced against the associated morbidity and mortality of surgery. Philosophically, the individual's best interest must be sought in light of the latest advances in medicine and science following discussions with a multidisciplinary team in specialist pancreatic centres.

Pancreatic hamartoma is a rare benign lesion and may be mistaken for a malignancy, as demonstrated by two cases. The first case was a 29-year-old man who presented with a 7-month history of intermittent upper abdominal pain, nausea and vomiting and a 15-kg weight loss. CT and MRI revealed a mass in the head of the pancreas. The second case was a 62-year-old man who presented with a 2-year history of intermittent abdominal pain, vomiting and a 25-kg weight loss. Although positron emission tomography was normal, CT revealed thickening of the duodenal wall and endoluminal ultrasonography revealed a tumour in the head of the pancreas. Both patients recovered from uneventful Kausch-Whipple pancreatoduodenectomy (in the first patient, it was pylorus-preserving), and in each case the histological diagnosis was hamartoma. Pancreatic hamartoma can present with vague, non-specific symptoms which, despite modern diagnostic tools, can be difficult to diagnose. Surgical resection with histopathological examination is required to confirm the diagnosis., (Copyright 2004 S. Karger AG, Basel and IAP.)