The ileoanal pouch has become the standard restorative procedure of choice for patients with the classical phenotype in FAP (familial adenomatous polyposis) and also for ulcerative colitis (UC). ...Whilst we tend to encounter descriptive analyses comparing functional outcome, fertility and quality of life (QOL) between series in literature, there may be an urgent need to discuss the subtle technical modifications that may be pivotal for improving long-term QOL in FAP patients. Our aim is to review the current literature and discuss the aspects of ileal pouch-anal anastomosis that may require specific reevaluation for FAP. Surgical strategies aimed at minimizing post-interventional desmoid growth is one of the most important aspects. For this study, the following topics of interest were selected: Timing of surgery, IRA or ileoanal pouch for classical FAP, laparoscopic or conventional surgery, TME or mesenteric dissection, preservation of the ileocolic vessels, handsewn or double-staple anastomosis, shape and size of pouch, protective ileostomy, Last and definitely not least: how to manage desmoid plaques or desmoids at the time of prophylactic surgery. For the depicted technicalities of the procedure, a review of recent literature was performed and evaluated. For the topics selected, only sparse reference in literature was identified that was focused on the specific condition situation of FAP. Almost all pouch literature focusses on the procedural aspects, and FAP patients are always a very minor number. Therefore it becomes obvious that the specific entity is not adequately taken into account. This is a serious bias for identification of important steps in the procedure that may be beneficial for patients with either of the diseases. The results of this study demonstrate that several technical differences for construction of ileoanal pouches in FAP patients deserve more attention and prospective evaluation—perhaps even randomized trials. The role, importance and potential benefit or deterioration of outcome in most of the discussed technicalities remains unclear to date. Significant differences between the underlying diseases (UC and FAP) have not been taken into consideration, such as specifically the management of precursor desmoid lesions at the time of prophylactic surgery as well as prevention of desmoid tumors. Several of the aspects discussed in this paper should be prospectively evaluated in larger and exclusive series of FAP patients.
Individuals with familial adenomatous polyposis (FAP) have an almost 20% lifetime risk of duodenal adenocarcinoma, currently the leading cause of death in FAP. The Spigelman staging system provides ...guidance on the surveillance intervals and timing of prophylactic surgery. Still, its accuracy in predicting duodenal and papillary cancer development has not been systematically evaluated. We investigated the sensitivity and cancer risk of the Spigelman stages.
We performed a systematic review on PubMed, MEDLINE, EMBASE, and Cochrane and used a random-effects model to pool effect sizes.
After removing duplicate entries, we screened 1,170 records and included 27 studies for quantitative analysis. Once duodenal polyposis reaches Spigelman stage IV, the risk of duodenal and papillary cancers increased to 25% (95% confidence interval CI 12%-45%). However, the sensitivity of Spigelman stage IV for these cancers was low (51%, 95% CI 42%-60%), especially for papillary adenocarcinoma (39%, 95% CI 16%-68%). We investigated the reasons behind these low values and observed that duodenal cancer risk factors included polyps >10 mm, polyp count >20, and polyps with high-grade dysplasia. Risk factors associated with papillary cancer included a papilla with high-grade dysplasia or >10 mm. The evidence on other risk factors was inconclusive.
The current Spigelman staging system had a low sensitivity for duodenal and papillary adenocarcinomas. Two Spigelman variables (duodenal villous histology and polyp count) and the lack of papilla-specific variables likely contributed to the low sensitivity values for duodenal and papillary cancers, respectively. While clinicians may be familiar with its current form, there is an urgent need to update it.
Purpose
The aim of the study was to investigate the underlying cause of long-term complications in patients requiring at least one revision surgery of a continent ileostomy (CI) and to analyze ...functional outcome.
Methods
Only patients with CI at least one revision were included in the retrospective data analysis. Four different classes of complications (Cl A–D) were defined: Cl A = Nipple valve (NV), Cl B = pouch, Cl C = outlet (stoma), and Cl D = afferent loop (AL). Associations between underlying disease and origin of complications were analyzed. Cumulative probabilities were calculated using Kaplan–Meier analysis.
Results
A total of 77 patients were identified with a follow-up of 30 years, requiring 133 surgeries for 148 complications (c.). Cl A 49 c. (33.1%), Cl B 50 c. (33.8%), Cl C 39 c. (26.4%), and Cl D 10 c. (6.8%). Cl A and C complications were not correlated to underlying disease, whereas Cl B and D complications were only found in ulcerative colitis (UC) and Crohn’s disease (CD). The cumulative probability of a second revision showed a linear rise, reaching 62.5% after 20 years. Cl A and B complications both reached 42.1%. Eleven (14.3%) patients (10 Cl B) had pouch failure in a follow-up period of 11.5 ± 8.7 years (1–31 years), whereas 66 (85.7%) had successful revisional surgery. Overall CI survival was 78.8% at 44 years.
Conclusion
CI survival is limited by inflammatory complications of the pouch based on the underlying disease and not by mechanical limitations of the NV.
Trial registration numbers
None.
Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy ...with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS‐associated CRC. Alongside with hypotheses addressing colonoscopy quality and pace of progression from adenoma to cancer, we discuss the role of alternative precursors and immune system in LS‐associated CRC. We also identify gaps in current knowledge and make suggestions for future studies aiming at improved CRC prevention for LS individuals.
The spectrum of somatic genetic variation in colorectal adenomas caused by biallelic pathogenic germline variants in the MSH3 gene, was comprehensively analysed to characterise mutational signatures ...and identify potential driver genes and pathways of MSH3-related tumourigenesis. Three patients from two families with MSH3-associated polyposis were included. Whole exome sequencing of nine adenomas and matched normal tissue was performed. The amount of somatic variants in the MSH3-deficient adenomas and the pattern of single nucleotide variants (SNVs) was similar to sporadic adenomas, whereas the fraction of small insertions/deletions (indels) (21-42% of all small variants) was significantly higher. Interestingly, pathogenic somatic APC variants were found in all but one adenoma. The vast majority (12/13) of these were di-, tetra-, or penta-base pair (bp) deletions. The fraction of APC indels was significantly higher than that reported in patients with familial adenomatous polyposis (FAP) (p < 0.01) or in sporadic adenomas (p < 0.0001). In MSH3-deficient adenomas, the occurrence of APC indels in a repetitive sequence context was significantly higher than in FAP patients (p < 0.01). In addition, the MSH3-deficient adenomas harboured one to five (recurrent) somatic variants in 13 established or candidate driver genes for early colorectal carcinogenesis, including ACVR2A and ARID genes. Our data suggest that MSH3-related colorectal carcinogenesis seems to follow the classical APC-driven pathway. In line with the specific function of MSH3 in the mismatch repair (MMR) system, we identified a characteristic APC mutational pattern in MSH3-deficient adenomas, and confirmed further driver genes for colorectal tumourigenesis.
Continent ileostomy (CI) aims to provide control of gas and faecal evacuation; however, it is rarely performed. This paper reports on outcomes of CI in a large single-surgeon series.
All consecutive ...patients who underwent CI between 1986 and 2015 were reviewed. Patients were classified according to the CI procedure (single stage versus two stage) and according to the underlying disease conditions (inflammatory bowel disease (IBD) versus no IBD). Primary outcome measures were early mortality and complications requiring surgical revision within 30 days (group Ia), those requiring surgical revision within 1-12 months (group Ib), and long-term complications after more than 12 months (group II). Secondary outcome measures were pouch survival and quality of life (QoL) assessed using questionnaires for occupational, sports, sexual, and travel activities; patients undergoing CI after conversion from ileostomy. Analyses were performed using descriptive statistics and Kaplan-Meier curves for the long-term outcomes.
Sixty-two consecutive patients (28 men, 34 women) who underwent CI were reviewed, including 48 with IBD, and 14 without inflammatory conditions. Mean(s.d.) follow-up was 14.4 (9.5) (range 1-30) years. Twenty-seven patients (44 per cent) developed group I complications, of which 25 were corrected successfully. Two patients dropped out of the analysis: one who died from sepsis and the other owing to pouch loss attributed to unsolvable nipple complications. Of the remaining 60 patients, 23 (38 per cent) developed between one and five group II complications. The cumulative probability of reoperation was 54. per cent at 25 years. Overall, pouch survival was achieved in 90 per cent. The two-stage approach led to significantly fewer complications in group Ia (single stage versus two stage: 8 of 25 versus 2 of 37; P = 0.005), whereas complication rates in group Ib (5 of 23 versus 14 of 37) and group II (9 of 23 versus 14 of 37) were similar. Four CIs failed because of IBD complications. CI pouch and function were preserved in all patients without IBD, whereas in the group with IBD 2 of 31 with ulcerative colitis and 2 of 17 with Crohn's colitis lost the CI owing to severe intractable inflammatory complications. In 16 patients who had conversion from ileostomy to CI, QoL improved significantly above precolectomy levels in all domains.
CI remains an alternative to conventional ileostomy. Although affected by high reoperation rates, it has the benefit of a high rate of pouch survival.
An effective biological marker for pancreatic adenocarcinoma (PAC) is not available so far. Here, we investigate how electron paramagnetic resonance (EPR) spectroscopy of spin-labeled fatty acid (FA) ...molecules binding to human serum albumin (HSA) in human serum is a suitable method for the identification of patients with PAC through detection of PAC-induced changes of FA binding to albumin. The functionality of HSA to bind FA is investigated in serum samples of 35 patients with PAC, 26 patients with benign pancreatic tumors (BPD), and 24 healthy individuals by continuous wave (CW) EPR spectroscopy by simply dissolving 16-DOXYL stearic acid as spin-labeled FA. It is found that FA binding to HSA in PAC is significantly modified when compared with healthy and BPD individuals. The PAC group could best be discriminated from the healthy group based on EPR characteristics at the loading ratio of 1:4 (HSA:FA), while patients with PAC and BPD are distinguishable at a loading ratio of 1:6. Using nanoscale distance measurements through double electron–electron resonance (DEER), it is found that the distribution of FAs in the HSA of one PAC patient is similar to that of FAs in healthy individuals. Combining all EPR spectroscopic data, this leads to a tentative molecular interpretation of only small changes in hydration at the protein’s surface as origin of the detectable characteristics for PAC patients. Thus, EPR of FA/HSA binding is a simple and promising tool for clinical detection of patients with PAC and needs to be tested with larger ensembles of different patient groups.
The current evidence to guide management of Peutz-Jeghers Syndrome (PJS) is sparse. Here we summarise the European guidelines that were published in 2021 by the EHTG (European Hereditary Tumour ...Group), extended with new evidence on some aspects of clinical management that have been generated since then. EHTG with this revised guideline has updated and extended their own previous expert opinion guideline from 2010. For this purpose, all published literature was systematically screened and the level of evidence determined by using the GRADE methodology (Grading of Recommendations Assessment. Development and Evaluation). This was followed by a Delphi process and the consensus for a statement was achieved if the voting committee reached ≥ 80% approval.The only other more recently published guidelines encountered only addressed the clinical management of gastrointestinal and pancreatic manifestations of PJS. These recommendations were reviewed and adopted, since no further relevant literature was identified in the systematic literature search. However, additional questions were identified and formulated into recommendations after following the described process. It may be stated that 10 years after the predecessor guideline, new evidence has been sparse. As with all rare diseases, a call for more collaborative studies must here be made in order to improve patient management by addressing open clinical questions and generating collaborative evidence with increased case numbers, both nationally and internationally. With the limited published evidence, these European guidelines are the most current reference for management of PJS patients.
Purpose
Prophylactic proctocolectomy with an ileoanal neo-reservoir is the established procedure in non-attenuated familial adenomatous polyposis (FAP). Traditionally, the ileal J-pouch is created by ...doubling 15 cm of the terminal ileum. Pouch inlet problems are not infrequently encountered in longer pouches. On this rationale, this series reports on the functional outcome and quality of life (QoL) following standardized construction of a shorter J-pouch with a limb of 8–9 cm length.
Methods
All patients of a single-surgeon series with FAP who underwent hand-assisted laparoscopic proctocolectomy and small ileal pouch-anal anastomosis as the primary procedure between 10/2005 and 04/2010 and responded to the questionnaire were included and retrospectively analyzed.
Results
A total of 46 patients (78 %) out of the consecutive series who underwent operation in this period were included in the study. After a mean follow-up of 38 months, 40/46 patients (87 %) did not report any incontinence and 3 patients (6.5 %) complained about occasional nocturnal incontinence (3 failed to answer this question). The mean stool frequency per 24 h was 6.25.
No significant difference was encountered between the QoL outcome of our patients versus the German normative population. Comparable results were achieved in a study analyzing the long-term results in FAP patients with a 15-cm pouch.
Conclusions
Smaller, 8–9 cm J-pouches show excellent functional results both in short- and in long-term results. The hand-assisted procedure was safe and no conversions were required. QoL is equal to a normative population, as it is in a series of patients with larger J-pouches.
PDF
