Age and manifestation related symptoms in familial adenomatous polyposis

BACKGROUND: To identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis. METHODS: We undertook a retrospective study of 143 FAP patients treated at the Department of Surgery, University of Erlangen between 1971 and 2000. We identified patterns of symptoms, endoscopic findings and extracolonic manifestations in three age groups. RESULTS: FAP was diagnosed clinically on the basis of symptoms in 84% (120/143) of these patients. Most presented with intestinal symptoms such as colonic bleeding (68%) and diarrhea (42%). All but one of the patients between 20 and 40 years old had rectal polyps (98.7%, 75/76), whereas in those over 40 years old the prevalence was 76% (35/46). Non-specific symptoms such as abdominal pain, fatigue and bloating were less frequent and were mainly reported by patients older than 40. CONCLUSION: The commonest presenting features of FAP are alteration of bowel habit and rectal bleeding, but both are found in many other conditions. Patients with these findings need immediate endoscopy to allow prompt diagnosis and prophylactic surgery

Cholinergic Signaling Attenuates Pro-Inflammatory Interleukin-8 Response in Colonic Epithelial Cells.

Infants affected by Hirschsprung disease (HSCR), a neurodevelopmental congenital disorder, lack ganglia of the intrinsic enteric nervous system (aganglionosis) in a variable length of the colon, and are prone to developing severe Hirschsprung-associated enterocolitis (HAEC). HSCR patients typically show abnormal dense innervation of extrinsic cholinergic nerve fibers throughout the aganglionic rectosigmoid. Cholinergic signaling has been reported to reduce inflammatory response. Consequently, a sparse extrinsic cholinergic innervation in the mucosa of the rectosigmoid correlates with increased inflammatory immune cell frequencies and higher incidence of HAEC in HSCR patients. However, whether cholinergic signals influence the pro-inflammatory immune response of intestinal epithelial cells (IEC) is unknown. Here, we analyzed colonic IEC isolated from 43 HSCR patients with either a low or high mucosal cholinergic innervation density (fiber-low versus fiber-high) as well as from control tissue. Compared to fiber-high samples, IEC purified from fiber-low rectosigmoid expressed significantly higher levels of IL-8 but not TNF-α, IL-10, TGF-β1, Muc-2 or tight junction proteins. IEC from fiber-low rectosigmoid showed higher IL-8 protein concentrations in cell lysates as well as prominent IL-8 immunoreactivity compared to IEC from fiber-high tissue. Using the human colonic IEC cell line SW480 we demonstrated that cholinergic signals suppress lipopolysaccharide-induced IL-8 secretion via the alpha 7 nicotinic acetylcholine receptor (a7nAChR). In conclusion, we showed for the first time that the presence of a dense mucosal cholinergic innervation is associated with decreased secretion of IEC-derived pro-inflammatory IL-8 in the rectosigmoid of HSCR patients likely dependent on a7nAChR activation. Owing to the association between IL-8 and enterocolitis-prone, fiber-low HSCR patients, targeted therapies against IL-8 might be a promising immunotherapy candidate for HAEC treatment

External validation of predictive models for diagnosis, management and severity of pediatric appendicitis

BackgroundAppendicitis is a common condition among children and adolescents. Machine learning models can offer much-needed tools for improved diagnosis, severity assessment and management guidance for pediatric appendicitis. However, to be adopted in practice, such systems must be reliable, safe and robust across various medical contexts, e.g., hospitals with distinct clinical practices and patient populations.MethodsWe performed external validation of models predicting the diagnosis, management and severity of pediatric appendicitis. Trained on a cohort of 430 patients admitted to the Children’s Hospital St. Hedwig (Regensburg, Germany), the models were validated on an independent cohort of 301 patients from the Florence-Nightingale-Hospital (Düsseldorf, Germany). The data included demographic, clinical, scoring, laboratory and ultrasound parameters. In addition, we explored the benefits of model retraining and inspected variable importance.ResultsThe distributions of most parameters differed between the datasets. Consequently, we saw a decrease in predictive performance for diagnosis, management and severity across most metrics. After retraining with a portion of external data, we observed gains in performance, which, nonetheless, remained lower than in the original study. Notably, the most important variables were consistent across the datasets.ConclusionsWhile the performance of transferred models was satisfactory, it remained lower than on the original data. This study demonstrates challenges in transferring models between hospitals, especially when clinical practice and demographics differ or in the presence of externalities such as pandemics. We also highlight the limitations of retraining as a potential remedy since it could not restore predictive performance to the initial level

Sacral nerve stimulation is a valuable diagnostic tool in the management of anorectal and pelvic malformations

Background: We hypothesize that the current practice of sphincter assessment in anorectal malformations (ARMs) by direct muscle stimulation can be improved by sacral nerve stimulation (SNS). Focusing on the specific adjustments for infants, we highlight the anatomical and neurophysiologic basis of SNS and its further diagnostic and therapeutic implications. Patients and Methods: We examined 20 patients: 12 patients with ARM, 3 with Hirschsprung disease, 3 with sacrococcygeal teratoma, and 2 with cloacal exstrophies. Under general anesthesia and ultrasound guidance, percutaneous needle electrodes were placed within the sacral neural foramina. Electrical stimulation was applied to assess the presence, pattern, and extent of the neuromuscular response of the external anal sphincter. Results: We successfully modified the traditional method used in adults replacing radiographic controls by ultrasound guidance. In 20 SNS procedures with no complications, we found a muscle response on stimulation of the third and/or fourth sacral nerves in 18 of 20 patients (anal sphincter contraction and/or ipsilateral plantar flexion). Conclusion: We demonstrated the feasibility of SNS for intraoperative sphincter mapping and detection of primary innervation abnormalities in ARM as well as for the assessment of secondary deficits in postoperative follow-up. Sacral nerve stimulation broadens the spectrum of intraoperative information concerning the sacral innervation pattern by a direct assessment of the sacral nerves. Furthermore, electrophysiologic data may allow prospective criteria for sphincter function to be established. These may improve the accuracy of the present classification-based prognosis as well as the understanding of sphincter physiology in general. (C) 2012 Elsevier Inc. All rights reserved

Forces to be overcome in correction of pectus excavatum

ObjectiveThe Erlangen technique of funnel chest correction is carried out through an anterior incision, and an essential step is retrosternal mobilization. After elevation of the funnel, the chest wall is stabilized with a lightweight transsternal metal implant. Forces necessary to elevate the chest wall were measured at defined intervals during the operation to prospectively assess the effect of peristernal and retrosternal dissection.MethodsOver a 3-year period, systematic tension measurements were carried out on 100 consecutive patients with symmetric funnel chest to assess the effect of individual steps in mobilization of the sternum.ResultsWhereas in adolescents the extraction force is about 175 N, in adults it is not possible to elevate the sternum to the desired level without surgical mobilization because the force required is, on average, more than 200 N. Only about 50% of this tension can be eliminated by costal chondrotomy. To reduce the tension further and achieve a stable result without the need for heavy-duty internal fixation, we carry out a retrosternal dissection, including removal of the slips of the diaphragm and the insertions of the transversus thoracis muscle. The mean tension at the end of the procedure is 25 N.ConclusionsOur measurements show that retrosternal dissection is the decisive step in the Erlangen technique, which might explain the low relapse rate and allow for a less extensive anterolateral mobilization