Issues for patchy tissues: defining roles for gut-associated lymphoid tissue in neurodevelopment and disease.

Individuals diagnosed with neurodevelopmental conditions such as autism spectrum disorder (ASD; autism) often experience tissue inflammation as well as gastrointestinal dysfunction, yet their underlying causes remain poorly characterised. Notably, the largest components of the body's immune system, including gut-associated lymphoid tissue (GALT), lie within the gastrointestinal tract. A major constituent of GALT in humans comprises secretory lymphoid aggregates known as Peyer's patches that sense and combat constant exposure to pathogens and infectious agents. Essential to the functions of Peyer's patches is its communication with the enteric nervous system (ENS), an intrinsic neural network that regulates gastrointestinal function. Crosstalk between these tissues contribute to the microbiota-gut-brain axis that altogether influences mood and behaviour. Increasing evidence further points to a critical role for this signalling axis in neurodevelopmental homeostasis and disease. Notably, while the neuroimmunomodulatory functions for Peyer's patches are increasingly better understood, functions for tissues of analogous function, such as caecal patches, remain less well characterised. Here, we compare the structure, function and development of Peyer's patches, as well as caecal and appendix patches in humans and model organisms including mice to highlight the roles for these essential tissues in health and disease. We propose that perturbations to GALT function may underlie inflammatory disorders and gastrointestinal dysfunction in neurodevelopmental conditions such as autism.

The Emerging Role of the Gut-Brain-Microbiota Axis in Neurodevelopmental Disorders.

Autism spectrum disorder (ASD; autism) is a prevalent neurodevelopmental disorder associated with changes in gut-brain axis communication. Gastrointestinal (GI) symptoms are experienced by a large proportion of individuals diagnosed with autism. Several mutations associated with autism modify cellular communication via neuronal synapses. It has been suggested that modifications to the enteric nervous system, an intrinsic nervous system of the GI tract, could contribute to GI dysfunction. Changes in gut motility, permeability, and the mucosal barrier as well as shifts in the large population of microbes inhabiting the GI tract could contribute to GI symptoms. Preclinical research has demonstrated that mice expressing the well-studied R451C missense mutation in Nlgn3 gene, which encodes cell adhesion protein neuroligin-3 at neuronal synapses, exhibit GI dysfunction. Specifically, NL3R451C mice show altered colonic motility and faster small intestinal transit. As well as dysmotility, macrophages located within the gut-associated lymphoid tissue of the NL3R451C mouse caecum show altered morphology, suggesting that neuro-inflammation pathways are modified in this model. Interestingly, NL3R451C mice maintained in a shared environment demonstrate fecal microbial dysbiosis indicating a role for the nervous system in regulating gut microbial populations. To better understand host-microbe interactions, further clarification and comparison of clinical and animal model profiles of dysbiosis should be obtained, which in turn will provide better insights into the efforts taken to design personalized microbial therapies. In addition to changes in neurophysiological measures, the mucosal component of the GI barrier may contribute to GI dysfunction more broadly in individuals diagnosed with a wide range of neurological disorders. As the study of GI dysfunction advances to encompass multiple components of the gut-brain-microbiota axis, findings will help understand future directions such as microbiome engineering and optimisation of the mucosal barrier for health.

Paediatric and adolescent traumatic gastrointestinal injuries: results of a European multicentre analysis.

AIM: Paediatric gastrointestinal injuries (GIIs) are rare, and the aim of this multicentre study was to evaluate their outcomes in a large cohort. METHODS: Hospital databases of 10 European paediatric surgical centres were reviewed for paediatric traumatic GIIs managed between 2000-2010. RESULTS: Ninety-seven patients with a median age of 9 years (0-17 years) were identified, with 72 blunt and 25 penetrating GIIs. Initial diagnostics in 90 patients led to correct diagnosis in 71%. Diagnostics were delayed in 26 patients (median 24 h). Eighty-two patients required surgery (67 laparotomy, 12 laparoscopy and three other approaches). There was a 50% conversion in the laparoscopic group. Median hospital stay was 10 days (range 1-137 days), with longer duration influenced by associated injuries (n = 41). Diagnosis <24 h was associated with significantly shorter hospital stay compared to more than 24 h (p = 0.011). In one-third of patients, morbidities were not related to a diagnostic delay or type of injury. There were five lethal outcomes, four due to associated injuries. CONCLUSION: Initial diagnostics in traumatic paediatric GIIs provide false negatives in one-third of patients. Diagnostic delay <24 h is associated with a significantly shorter hospital stay. Although laparoscopy is associated with a conversion rate of 50%, it can be used for diagnosis in suspected cases to avoid nontherapeutic laparotomy.

Transanal pull-through procedure for Hirschsprung's disease: a 5-year experience.

BACKGROUND/PURPOSE: Transanal endorectal pull-through (TEPT) has become a widely used approach for the treatment of Hirschsprung's Disease. The technique is safe and, according to previous reports, it has a good clinical outcome. In this study our experience with TEPT in the early postoperative period is evaluated. METHODS: The clinical course of 34 children (28 boys and 6 girls) who underwent one-stage pull-through operation according to De la Torre for Hirschsprung's disease from January 2003 to December 2007 was reviewed. Their ages ranged from 2 months to 4 years. Complications occurring within the first four weeks after operation were analyzed. RESULTS: Eight of 34 children (24 %) had early complications in the form of dehiscences of the anastomosis. Two children (6 %) had symptomatic anastomotic dehiscences. One child had an almost full retraction of the colon that had to be pulled down and resutured. One child developed a retrorectal abscess three weeks postoperatively due to anastomotic leakage. The dehiscences of 6 children (18 %) were asymptomatic. These dehiscences were detected only with standardized routine examination. The dehiscences healed uneventfully after resuturing. Two other patients (6 %) developed an anastomotic stricture that could be treated with rectal dilatations. Four children (12 %) showed a single episode of postoperative enterocolitis. CONCLUSION: The rate of early clinical and particularly subclinical complications such as anastomotic dehiscences after TEPT is higher than previously estimated. Patients should be monitored carefully during the early postoperative period. Severe complications can only be avoided with a thorough examination. Early resuturing of dehiscences might be helpful to prevent hazardous sequelae.

[Which paediatric urological procedures can be performed in a general hospital?]. / Was ist an kinderurologischen Eingriffen in einem Versorgungskrankenhaus machbar?

Principally, surgical procedures in children should be performed in specialized pediatric centers. Some minor procedures on older children could eventually take place in general hospitals, provided that pediatric medical and nursing competence is available. Adequate infrastructure and an environment appropriate for children are required as well. The comfort of therapy in an adjacent general hospital should not lead to an increased risk for the child. Principles of clinical diagnosis and treatment strategies of frequent pediatric urological entities are described and discussed in this article.

[Treatment of lymphangiomas with picibanil in the first year of life]. / Behandlung von Lymphangiomen mit Picibanil im ersten Lebensjahr.

BACKGROUND: The therapeutic gold standard of cystic hygroma is its complete resection. Because of its growth pattern and its main location in the head and neck region complete resection is not always possible. An alternative is the local injection of Picibanil, but only few cases have been published about its use in infants. PATIENTS/METHOD: We retrospectively analyzed the data of 8 infants (age: 2 weeks-12 months) who got Picibanil therapy because of cystic hygroma in the time period 2002 until 2006. Follow up ranged from 3 months up to 3 years. RESULTS: During the postoperative period all patients had local swelling, in 4 cases accompanied with local inflammation and fever. Tumor reduction of >50% was obtained in 7 of 8 patients. CONCLUSIONS: Local injection of Picibanil in infants with cystic hygroma seems to be a safe alternative to surgical therapy, especially when complete tumor resection means damage of important neighbouring structures. Prospective trials are necessary to confirm the better outcome after therapy with Picibanil compare to primary surgery.

Experience of 49 longitudinal intestinal lengthening procedures for short bowel syndrome.

PATIENTS, METHODS AND RESULTS: Forty-nine patients with a mean age of 25 months underwent a longitudinal intestinal lengthening procedure for short bowel syndrome (SBS) in our institution. Indications for the operation were dependence on parenteral nutrition in spite of adequate conservative management. The small bowel was lengthened from a mean of 27 cm to a mean of 51 cm. There was no intraoperative mortality. The following early complications occurred in our early series: ischemia of a short bowel segment of 2 cm, requiring resection in two patients, insufficiency of the longitudinal anastomosis in two patients and an intra-abdominal abscess in one. Four of 9 non-survivors died of liver failure and 3 of sepsis. Follow-up showed that 19 patients were weaned from parenteral nutrition after a mean of 9.1 months. Long-term complications encountered were dismotility with malabsorption due to bacterial overgrowth caused by progressive dilatation of the bowel, d-lactic acidosis, cholelithiasis and urolithiasis. CONCLUSIONS: A longitudinal intestinal lengthening procedure is an effective and safe surgical approach for SBS, provided it is performed in time, the patient's preoperative condition is optimized and technical surgical details are taken into account.

[Fetal surgery]. / Fetale Chirurgie.

Fetal surgery is a newly evolving multidisciplinary medical field, being performed in specialized centers. It deals with the treatment of selected fetuses with congenital anomalies that cause high morbidity and mortality. The aim of the surgical treatment is to avoid the development of progressive and eventually irreversible damage at birth. Examples of entities treated are obstructive uropathy leading to renal insufficiency, lung hypoplasia in severe congenital diaphragmatic hernia, severe congenital cystic adenomatoid malformation of the lung, and sacrococcygeal teratoma. This review describes principles of fetal surgery, physiopathologic processes of some of the anomalies treated in this way, and diagnostic and therapeutic approaches. Recently published results are presented and discussed.

[Reducing trauma by minimally invasive surgery from the viewpoint of pediatric surgery]. / Traumareduktion durch MIC aus der Sicht der Kinderchirurgie.

Reduced insufflation pressure during laparoscopy in pediatric surgery can contribute considerably to reducing postoperative pain. Technical innovations in high-grade instruments and thin optics have led to increased diversification of minimally invasive surgery and reduced the strain on patients. The minimally invasive approach is particularly advantageous when the large surgical approaches of conventional procedures can be avoided. The reduction of postoperative adhesions with minimally invasive surgery is a very important factor. The tendency toward decreased infections of surgical wounds is beneficial as well as the improved cosmetic results. The duration of hospital stays and need for analgesics in pediatric surgery have not evidenced any significant differences from conventional procedures. In cases of larger intra-abdominal interventions, it becomes apparent that these small patients can receive oral alimentation at an earlier time.

Minimally invasive repair of pectus excavatum--the Nuss procedure. A European multicentre experience.

Since the first description in 1998, the minimally invasive repair of pectus excavatum has gained increasing acceptance. The aim of this survey is to report on the experiences of eight European centres with this technique. 172 patients with a mean age of 15.1 (+/- 4.6) years were treated and evaluated, 35.5 % were symptomatic. 45.3 % of the patients had an asymmetric configuration of the chest, 74.3 % had a CT index above 3.25. Mean duration of the operative procedure was 76 minutes. Major complications, including dislocation of the bar or stabiliser, pneumonia, atelectasis, local infection, pleural and pericardial effusion and liver injury occurred in 11.1 % of the patients. Minor complications, such as self-resolving pneumothorax, atelectasis and subcutaneous emphysema were reported in another 8.1 %. Early cosmetic results were excellent or good in 81.5 %. Although the surgical procedure is simple, blood-sparing and short, consideration of some important technical details, proper patient selection and knowledge of the limitations is of vital importance. Long-term results are still lacking.

Segmental dilatation of the jejunum resembling prenatal volvulus.

A case of prenatally diagnosed intestinal obstruction caused by segmental dilatation of the jejunum is presented. Routine ultrasound scan showed mild polyhydramnios, a dilated small bowel loop, and scoliosis. On repeat ultrasound scan a volvulus was suspected, which led to cesarean section and laparotomy of the newborn, revealing the underlying pathology. Segmental resection and end-to-end anastomosis were followed by an uneventful recovery. Segmental dilatation of the intestine should be considered as a cause of prenatally manifested intestinal obstruction. Concomitant anomalies are frequent and may be helpful in making the correct diagnosis. J Pediatr Surg 36:927-929.

Management of kidney injuries in children with blunt abdominal trauma.

BACKGROUND/PURPOSE: The authors analyzed the incidence and the course of renal injuries encountered in a cohort of pediatric patients with blunt abdominal trauma. This review focuses on the early diagnostic and therapeutic approach rather than the long-term outcome and draws conclusions for an effective initial management. METHODS: From 1976 to 1996, the charts of 308 children with blunt abdominal trauma that were admitted to the authors' department were reviewed. The patients initially were evaluated using urinalysis, ultrasonography, and abdominal paracentesis (until 1984) and in specific cases iv-urography, computed tomography (CT), and angiography. The authors retrospectively classified the renal trauma after the widely used Organ Injury Scaling (OIS) into 5 grades and correlated the diagnostic value of various techniques as well as the diagnostic approach. RESULTS: Sixty-nine serious abdominal traumas were encountered. Thirty-six patients suffered renal lesions grade 2 (G2) or higher; 20 children were polytraumatized. There were 67 renal lesions including 28 G1, 22 G2, 8 G3, 5 G4, 1 G5, and 3 lesions of the lower urinary tract. Ultrasonography and urinalysis were found to be the optimal diagnostic methods for screening and following the course of renal injury. CT scan proved to be most reliable for detecting and exactly classifying renal lesions grade 2 or higher and superseded consecutively iv-urography. In cases in which CT scan failed to show renal excretion of contrast agent, angiography was performed. Ten patients proceeded to operative therapy. CONCLUSIONS: Ultrasonography and urinalysis proved to be the optimal initial evaluation tool for excluding renal injury both as a screening method and for further controls. Exact classification was possible by CT scan. During the reviewed time period a shift from surgical to conservative management was notable. If lesions were G4 or G5, surgical treatment with tendency toward minimally invasive therapy always was indicated.

Is there a correlation between organochlorine compounds and undescended testes?

Some pesticides and synthetic chemicals are known to act as hormonal modulators, often possessing oestrogenic activity (xenooestrogens). They are persistent and accumulate in fatty tissue. Aim of our study is to address the question, whether a selection of such compounds is to be found in the fatty tissue of children undergoing surgical procedures and whether there are differences in values obtained from patients with or without undescended testes. Fat samples of 48 patients, 18 of whom had undescended testes, were examined by high-resolution gas chromatography and mass spectrometry for DDT and metabolites, polychlorinated biphenyls (PCB), toxaphenes, hexachlorocyclohexane (HCH), chlorinated cyclodienes and chlorinated benzenes. We were able to find accumulation of all substances in every patient. Statistical analysis revealed a highly significant difference between patients from the control group and those from the undescended testes group for two compounds, namely heptachloroepoxide (HCE) and hexachlorobenzene (HCB), increased values being found in the patients with undescended testes. Since the aetiology of this entity is unknown in most of the cases, prenatal exposure to exogenous oestrogens is an attractive and plausible hypothesis. In order to confirm this, some questions will have to be answered in further studies: effect of exposure to xenooestrogens during a specific period of development, probable role of other substances with proven or suspected hormonal activity, potential synergism of such compounds and differences in individual susceptibility.

What do children look like after longitudinal intestinal lengthening.

The longitudinal intestinal lengthening, described by Bianchi in 1980, has been shown to be effective in improving intestinal function, absorption and transit time in patients with short-bowel syndrome. We report the long-term results of 18 survivors of a series of 25 intestinal lengthening procedures performed since 1984. Mean age of the patients was 18 months (range of 5 to 52 months), mean follow-up 6 years (0.9 to 12 years). Parenteral nutrition was progressively reduced in all patients and discontinued after 1 to 10 months (mean 5.1 months). Frequently encountered problems during long-term follow-up are hyperphagia, hyponatremia and hypochloremia, metabolic acidosis, including D-lactic acidosis, cholelithiasis and urolithiasis, gastro-esophageal reflux, dystrophy and symptoms caused by secondary dilatation of the lengthened bowel loops: a protruding abdomen, enteral stasis, leading to constipation or diarrhea with bacterial overgrowth. Overall performance has been acceptable in 13 out of 18 patients. Longitudinal intestinal lengthening is effective enabling patients with short-bowel syndrome to be weaned from parenteral nutrition, allowing for long-term survival. However, it is only one step on a long and difficult way. Multiple problems have to be searched for and adequately dealt with to achieve an acceptable and future worth living.

Parenteral nutrition-induced hepatobiliary dysfunction in infants and prepubertal rabbits.

We analyzed clinical, biochemical, and histo- logic parameters of ten infants with parenteral nutrition-induced hepatobiliary dysfunction. The data were compared with the results of a rabbit model. All infants were born prematurely with low birth weight. Their clinical diagnoses were necrotizing enterocolitis (6), gastroschisis (1), intrauterine volvulus (1), and lung hypoplasia (2). All required total (TPN) or partial parenteral nutrition for at least 8 weeks. All had repeated episodes of infections or sepsis. A rise in bilirubin and aminotransferase levels occurred after a minimum of 5 weeks; peak bilirubin levels ranged from 4 to 14 mg% and aminotransferases from 40 to 140 IU/l. One child later developed gallstones. Liver biopsies after 1 to 24 months showed fibrosis, bile-duct proliferation, cholestasis, and hydropic degeneration. All of the above-mentioned clinical factors have been accused of causing the observed biochemical and histologic changes. In our rabbit model we were able to produce almost identical symptoms by TPN alone: gallbladder distension, sludge, and stones developed after 1-4 weeks of TPN as well as uncharacteristic changes in aminotransferases and bilirubin after 4 weeks. Liver histology revealed severe hydropic degeneration of zone 3 as early as 1 week after beginning TPN. A rise of fibrosis and bile-duct proliferation after 1 to 4 weeks of infusion was statistically significant. Cholestasis, as was observed in the infants, could not be detected. In our model, all alterations observed could be attributed exclusively to TPN. We therefore assume that TPN was the true cause of the dysfunction. In a second experimental series infusions were reduced to 80% PN and free access to lab chow. These animals produced normal feces, indicating physiologic enteral stimulation. They developed the same degenerative and proliferative histologic changes, whereas gallbladder distension, sludge, and stones were not noted. We conclude that: (1) The TPN solution itself is responsible for the histologic changes in the liver, which is supported by the fact that hydropic degeneration of zone 3 is typical of a direct toxic effect; and (2) Complete enteral starvation with an absence of enteral stimulation causes disease of the lower biliary tract.

Could testicular descent in humans be promoted by direct androgen stimulation of the gubernaculum testis?

Gubernaculum testis and androgens play an important role in physiologic testicular descent. A direct androgen stimulation of the gubernaculum is only possible in the presence of specific receptors, which have not yet been demonstrated. We have determined the androgen-binding capacity in 61 samples of gubernaculum testis from 48 patients, 34 samples belonging to patients with maldescended testes. In 43 out of 61 instances we found androgen binding with values up to 72 fmol/mg, with a mean of 13.08 fmol/mg. In 27 samples from patients with a deep scrotal positioned gonad the mean androgen-binding capacity was 18.74 fmol/mg. In 10 samples from patients with a gonad in the proximal scrotum and 19 patients with epifascial ectopy or a low inguinal position the mean androgen-binding capacities decreased progressively to 9 fmol/mg and 5.95 fmol/mg. In the 5 samples from patients with high inguinal or abdominal testes the binding capacity of 17.8 fmol/mg did not significantly differ from the value obtained in the samples of the normal-positioned gonads, suggesting that transabdominal descent is probably not androgen-dependent. We divided the probes into receptor status positive for a binding capacity higher than or equal to 10 fmol/mg, and receptor status negative for a binding capacity under 10 fmol/mg. 63% of the samples from patients with scrotal positioned testes were receptor status positive, 85% of the samples belonging to patients with maldescended testes were receptor status negative. Receptor status was negative in patients with high scrotal, epifascial or low inguinal and high inguinal or abdominal testes in 90%, 95% and 40% of the samples respectively. Immunohistochemical examination of 10 samples showed small cell groups with stained nuclei in 2 out of 5 patients with normal-positioned testes. All other samples were negative. These findings prove that hormone binding was accomplished by specific intranuclear receptors. These findings allow for the first time the hypothesis of a direct androgen stimulation of the human gubernaculum testis. The probable mechanism is an increase in mucopolysaccharides leading to a swelling of the gubernaculum, dilating the inguinal canal and promoting testicular descent. Although certainly a multifactorial process, quality and quantity of androgen receptors would influence the extent of transinguinal testicular descent.

[Differentiation of sphincter insufficiency and constipation after surgical anal atresia treatment: value of a new continence score]. / Differenzierung von Sphinkterinsuffizienz und Obstipation nach operierter Analatresie: Wertigkeit eines neuen Kontinenzscores.

Surgery of anorectal malformations was evaluated by continence scores, excluding constipation. The authors introduce a new score considering the case history and clinical parameters that differentiate sphincter insufficiency and overflow-incontinence due to constipation.