Skipped Aganglionic Lengthening Transposition (SALT) is highly effective to achieve enteral autonomy in selected patients with intestinal failure secondary to total intestinal aganglionosis.

BACKGROUND: Intestinal Failure, parenteral nutrition (PN) dependence, and subsequent liver disease are the most challenging and life-threatening complications of short bowel syndrome experienced by patients with total intestinal aganglionosis. Skipped Aganglionic Lengthening Transposition (SALT) showed to be a promising procedure to overcome such problems. We herein report the results of two patients who underwent SALT at the Umberto Bosio Center for Digestive Diseases. PATIENTS AND METHODS: Between November 2019 and July 2022, 2 patients with total intestinal aganglionosis underwent SALT as autologous intestinal lengthening procedure. Perioperative data and long-term outcomes are reported. Patient #1-A 18 month-old male (PN dependant) with 30 cm of ganglionated bowel at birth experienced a 35% increase of intestinal length after SALT (from 43 to 58 cm) thanks to three 5 cm interposed aganglionic loops. Postoperative course was uneventful and he was totally weaned by PN after 28 months postoperatively. He is without PN only receiving enteric feeding 53 months after the procedure. Patient #2-A 11 year-old female (PN dependant) with 100 cm of ganglionated jejunum underwent SALT at 11 years and experienced a 19% increase of bowel length thanks to four 5 to 7 cm interposed aganglionic loops. Postoperatively she required excision of two out of the four loops due to severe strictures and inadequate perfusion with a subsequent overall 10% increase of length after SALT. Of note, she improved significantly with a progressive reduction of PN that has been stopped after 18 months. CONCLUSION: Skipped aganglionic lengthening transposition (SALT) seems to be very effective in improving nutrients absorption in patients with total intestinal aganglionosis by increasing absorptive bowel surface and decelerating intestinal flow for a longer and more effective contact of enteric material with ileal mucosa. Provided these impressive results are confirmed in the very long-term, SALT could become a valid alternative for the treatment of patients with total intestinal aganglionosis carrying at birth at least 20 to 30 cm of ganglionated jejunum.

A unicentric cross-sectional observational study on chronic intestinal inflammation in total colonic aganglionosis: beware of an underestimated condition.

BACKGROUND: Inflammatory Bowel Diseases (IBD) are known to occur in association with Hirschsprung disease (HSCR). Most of cases are represented by Crohn Disease (CD) occurring in patients with Total Colonic Aganglionosis (TCSA) with an estimated prevalence of around 2%. Based on these considerations and on a number of provisional data belonging to our Center for Digestive Diseases, we developed a unicentric cross-sectional observational study aimed at describing phenotype, genotype, pathology and metagenomics of all patients with TCSA and Crohn-like lesions. RESULTS: Out of a series of 62 eligible TCSA patients, 48 fulfilled inclusion criteria and were enrolled in the study. Ten patients did not complete the study due to non-compliance or withdrawal of consent and were subsequently dropped out. A total of 38 patients completed the study. All patients were tested for chronic intestinal inflammation by a combination of fecal calprotectine (FC) or occult fecal blood (OFB) and underwent fecal metagenomics. Nineteen (50%) tested positive for FC, OFB, or both and subsequently underwent retrograde ileoscopy. Fourteen patients (36.8%) presented Crohn-like lesions, occurring after a median of 11.5 years after surgery (range 8 months - 21.5 years). No statistically significant differences regarding demographic, phenotype and genotype were observed comparing patients with and without lesions, except for need for blood transfusion that was more frequent in those with lesions. Faecal microbiome of patients with lesions (not that of caregivers) was less biodiverse and characterized by a reduction of Bacteroidetes, and an overabundance of Proteobacteria. FC tested negative in 3/14 patients with lesions (21%). CONCLUSIONS: Our study demonstrated an impressive 10-folds higher incidence of chronic inflammation in TCSA. Up to 50% of patients may develop IBD-like lesions postoperatively. Nonetheless, we failed in identifying specific risk factors to be used to implement prevention strategies. Based on the results of our study, we suggest screening all TCSA patients with retrograde ileoscopy regardless of FC/OFB values. The frequency of endoscopic assessments and the role of FC/OFB screening in prompting endoscopy is yet to be determined.

Case report: Gastroenterological management in a case of cardio-facio-cutaneous syndrome.

Background: cardio-facio-cutaneous syndrome is a rare genetic disorder affecting less than 900 people in the world. It is mainly characterized by craniofacial, dermatologic and cardiac defects, but also gastroenterological symptoms may be present, ranging from feeding difficulties to gastroesophageal reflux and constipation.In this report we describe a case of this syndrome characterized by severe feeding and growth difficulties, with a particular focus on the management of gastroenterological complications. Case presentation: the patient was a caucasian male affected by Cardio-Facio-Cutaneous syndrome who presented feeding difficulties already a few hours after birth. These symptoms worsened in the following months and lead to a complete growth arrest and malnutrition. He was first treated with a nasogastric tube placement. Subsequently, a laparoscopic Nissen fundoplication and a laparoscopic Stamm gastrostomy were performed. The child was fed with nocturnal enteral nutrition and diurnal oral and enteral nutrition. Eventually the patient resumed feeding validly and regained adequate growth. Conclusion: this paper aims to bring to light a complex rare syndrome that infrequently comes to the attention of the pediatricians and whose diagnosis is not always straightforward. We also highlight the possible complications under a gastroenterologic point of view. Our contribution can be helpful to the pediatrician in the first diagnostic suspect of this syndrome. In particular, it is worth highlighting that -in an infant with Noonan-like features- symptoms like suction or swallowing problems, vomiting and feeding difficulties should orient towards the diagnosis of a Cardio-facio-cutaneous syndrome. It is also important to stress that its related gastroenterological issues may lead to severe growth failure and therefore the role of the gastroenterologist is key to manage supplemental feeding and to establish whether a nasogastric or gastrostomic tube placement is necessary.

A novel mutation in GCK gene: Beware of SGA child with diabetic mother.

MODY is a monogenic, autosomal dominant form of diabetes mellitus. MODY can be caused by mutations in several genes; glucokinase (GCK) accounts for 30-50% of the cases. The diagnosis can be suspected in early-onset diabetes with atypical features for type 1/type 2. Treatment is usually not recommended. A 5-year-old girl came to our attention for occasional episodes of hyperglycaemia. She was born at term, her birth weight was small for gestational age. At the beginning of her pregnancy, her mother was already on insulin therapy for impaired fasting glucose levels, detected before conception and confirmed in the first weeks of gestation. She was treated with insulin until the childbirth without further investigations. The patient was asymptomatic and in good clinical condition. Basal blood tests have shown a fasting plasma glucose of 125 mg/dl, an HbA1c of 6.5%. Antibodies against islet cells, anti-GAD and anti-ZNT8 antibodies were all negative. A 2-h oral glucose tolerance test was performed and underlined an impaired glucose tolerance. HLA haplotypes were screened, excluding susceptibility. GCK Sanger Sequencing identified a novel heterozygous variant. It is not described as a classical mutations. The analysis has been extended to the parents, finding out the same variant in her mother. To our knowledge this mutation has not been described previously; we believe that this variant is responsible for MODY2 due to FBG and Hb1Ac of all the affected members of family. We suggest high suspicion of an underlying GCK variant in SGA children with hyperglycaemia born to a diabetic mother.

Skipped aganglionic lengthening transposition (SALT) for short bowel syndrome in patients with total intestinal aganglionosis: technical report and feasibility.

Extended aganglionosis (TIA) is the presence of some viable aganglionic gut distal to the levelling jejunostomy. Different surgical procedures (including transplantation) have been proposed with inconclusive results. We conceived a new procedure named skipped aganglionic lengthening transposition (SALT) consisting of multiple pedicled isoperistaltic transpositions of aganglionic ileal loops interposed to normoganglionic jejunum. The innovative aspect consists of taking advantage of the propulsive effect of normoganglionated bowel to progress enteric content throughout interposed aganglionic loops down to the stoma. The procedure was adopted in a male patient who was born with 30 cm of normoganglionated jejunum. SALT was performed when the baby was 18 months. Three 5-cm pedicled isoperistaltic aganglionic loops of small bowel were interposed each 10 cm of normoganglionic jejunum with an overall 36% length gain (from 42 to 57 cm). Postoperative course was uneventful. 6 months postoperatively, an upper gastrointestinal series showed normal progression without dilatations. A laparoscopic gastrostomy was performed due to food aversion 6 months postoperatively, demonstrating impressive anatomic and functional postoperative results. The procedure provides promising and unique opportunity for patients with TIA with encouraging outlook for the near future.

A polymorphic variant inside the osteopontin gene shows association with disease course in oligoarticular juvenile idiopathic arthritis.

BACKGROUND: Oligoarticular onset juvenile idiopathic arthritis (JIA) has a variable disease course. In some patients the disease remains confined to a few joints (persistent oligoarticular) while in others it extends to affect more joints (oligoarticular extended). Osteopontin is thought to play a role in the pathogenesis. OBJECTIVE: To investigate whether a polymorphic variant in the human osteopontin gene, which is in linkage disequilibrium with recently characterised promoter variants, is associated with the disease course in oligoarticular JIA. METHODS: Genotyping of the two base pair insertion/deletion variant at +245 in the first intron was undertaken by polymerase chain reaction (PCR) amplification of DNA fragments, using a fluorescently labelled primer, followed by allele detection after rapid separation of PCR products on an automated DNA sequencer. RESULTS: Allele 2 of the polymorphic variant in the osteopontin first intron was significantly associated with the persistent oligoarticular form rather than the extended form of JIA. This was verified at the level of genotype and allele frequencies. CONCLUSIONS: The results suggest that osteopontin gene polymorphism is associated with the disease course in oligoarticular JIA and might therefore represent a useful genetic marker to characterise patients with oligoarticular JIA who are at risk of a worse outcome.

Unilateral destructive wrist synovitis in juvenile idiopathic arthritis.

OBJECTIVE: To describe the clinical and radiographic features of a group of juvenile idiopathic arthritis (JIA) patients who developed unilateral destructive wrist synovitis. METHODS: All wrist radiographs performed yearly between 1986 and 2002 in JIA patients who had wrist involvement were retrospectively reviewed to identify patients who had unilateral erosive wrist synovitis, defined as a difference of at least -3 units in the Poznanski score between the affected wrist and the unaffected wrist, with the Poznanski score in the unaffected wrist being > -2 units throughout the follow-up period. Clinical and radiographic data obtained during follow-up were recorded for all patients. RESULTS: Of a total of 250 patients for whom we had approximately 900 wrist radiographs, 6 patients were found to have unilateral erosive wrist synovitis. The JIA onset subtype was oligoarticular in 5 patients and polyarticular in 1 patient and the disease duration from presentation to the last follow-up visit ranged from 2 to 16 years. The arthritis course was polyarticular in all patients. Five patients had positive antinuclear antibodies (ANA) and 1 had positive rheumatoid factor (RF). At the last follow-up visit, all patients had some impairment of wrist function and 2 patients had wrist subluxation. There was a marked radiographic damage in all affected wrist, with the Poznanski ranging from -8.0 to -8.50 units in 3 patients and being -5.5, -3.1 and -2.4 units, respectively, in 3 patients. The severity of radiographic damage in the ANA-positive patients with the longest disease duration was comparable to that observed in the RF-positive patient. CONCLUSION: Unilateral erosive wrist synovitis seems to be uncommon in JIA. Patients with unilateral wrist synovitis may be at risk of a destructive course irrespective of the JIA onset subtype.

Synovial expression of osteopontin correlates with angiogenesis in juvenile idiopathic arthritis.

OBJECTIVE: To evaluate the synovial expression of osteopontin (OPN) and its possible correlation with the degree of synovial angiogenesis in human chronic idiopathic arthritis. METHODS: Forty-five patients with active juvenile idiopathic arthritis (JIA) were studied. All patients underwent SF aspiration before steroid injection. A paired plasma sample was collected from 22 JIA patients. Plasma from 15 age-matched healthy subjects was used as control. Plasma and SF were tested by ELISA for OPN and vascular endothelial growth factor (VEGF). Synovial tissue was obtained at synovectomy from 10 JIA patients. Immunohistochemistry was performed according to a standard technique with anti-OPN, anti-CD68, anti-CD31 anti-VEGF and anti-alpha(v)beta(3) antibodies. RESULTS: OPN levels were significantly higher in SF than in paired plasma samples (P<0.001). The same pattern was observed for VEGF (P<0.001). A positive correlation between OPN and VEGF concentrations was found in SF (r = 0.6, P = 0.001). In synovial tissue, OPN was expressed at the level of the lining and sublining layers with a distribution similar to that observed for VEGF. OPN expression in the lining layer correlated with the number of vessels present in the areas underlying the sublining layer. CONCLUSIONS: Synovial expression of OPN correlates with parameters of angiogenesis in JIA. These data support, in human disease, the possible role of OPN in the vascularization of inflamed synovial tissue, as previously shown in OPN-deficient animal models of arthritis.

Antegrade ureterolitholapaxy in the treatment of obstructing or incarcerated proximal ureteric stones.

Extracorporeal shockwave lithotripsy (ESWL) and retrograde ureterorenoscopy (RU) have transformed the management of ureteric calculi. Nevertheless, patients with obstructing proximal ureteric calculi are not suitable for ESWL or RU. From January 1986 to September 1988, 17 patients with fixed upper ureteric stones underwent antegrade renoureteroscopy and percutaneous surgery. The technique was effective in removing incarcerated proximal ureteric calculi: all patients were stone-free at follow-up 3 months later.

[Cancer of the prostate. Clinical estimation and results of radical prostatectomy]. / Cancer de la prostate. Appréciation clinique et résultats de la prostatectomie radicale.

The authors present their experience about the accuracy of staging and the results of radical prostatectomy in prostatic cancer. From january 1978 to september 1988, 47 patients with clinically localized prostatic carcinoma underwent staging pelvic lymphadenectomy, of whom 36 had proven negative pelvic lymph nodes and 1 had only a micrometastasis in the obturatory nodes. We reviewed the surgical results and survival of these 37 patients who underwent radical prostatectomy. The postoperative complications were compared to those reported in Literature: partial incontinence occurred in 3 patients and there were no symptomatic urethral strictrues. 1 patient died in the early postoperative period by DIC. 35 patients are alive, 27 free of disease, with average follow-up of 36 months. The over-all accuracy of staging was 87%. Our experience suggests that radical prostatectomy with staging bilateral pelvic lymphadenectomy can be performed in a safe manner with minimal postoperative morbidity.

Multiple simultaneous bilateral urothelial tumours of the renal pelvis.

Three cases of simultaneous bilateral transitional cell carcinoma of the renal pelvis are reported. In one case the bladder and urethra were also involved. The information provided by radiological studies (particularly renal angiography) and cytology allowed us to define with accuracy not only tumour sites but also the tumour itself and the degree of malignancy. Based on the latter finding, the surgical approach was adapted to each individual case and consisted of papillectomy, partial pyelectomy or heminephrectomy associated with contralateral nephroureterectomy. In one case total cystourethrectomy was performed. Long-term follow-up showed no recurrence in the residual urinary tract 5 to 8 years post-operatively.

[Anticholinergic treatment in the therapy of primary enuresis. Effectiveness of oxybutynin chloride in a controlled clinical study of 58 patients]. / II trattamento anticolinergico nella terapia della enuresi essenziale. Efficacia dell'ossibutinina cloruro in uno studio clinico controllato su 58 pazienti.

2 groups of enuretic children were respectively treated with anticholinergic drugs dicyclomine and oxybutynin chloride. The results of the trial clearly indicate oxybutynin as the most effective drug in the treatment of the disease.

[Retroperitoneal hematoma caused by a renal angiomyolipoma (review of the literature and diagnostic-therapeutic considerations)]. / Ematoma retroperitoneale da angiomiolipoma renale (revisione della letteratura e considerazioni diagnostico-terapeutiche).

The authors describe a case of perirenal hematoma, secundary to the breakage of an angiomyolipoma which appeared to their observation under the classic Wunderlich' syndrome. After shortly reviewing the preoperative diagnostic chances, they, as a conclusion, affirm that, unfortunately, the most rational treatment in case of isolated AML still consists of nephrectomy, because of the possible diagnostical mistakes and the concomitance of malignant neoplastic diseases.

Separation and characterization of NAD- and NADP-specific succinate-semialdehyde dehydrogenase from Escherichia coli K-12 3300.

Two distinct proteins endowed with succinate-semialdehyde dehydrogenase (succinate-semialdehyde:NAD(P)+oxidoreductase, EC 1.2.1.16) activity were separated and partially purified by ammonium sulphate fractionation or Sephadex G-200 gel-filtration or both. They differ by coenzyme specificity (NAD or NADP), molecular weight, temperature and pH resistance, pH-activity curves, beta-mercaptoethanol activation. Moreover, the NADP-specific enzyme catalyzes only the oxidation of succinate-semialdehyde among a number of aldehydes tested, whereas the NAD-specific form is active also towards n-butyraldehyde. The Km for the substrate is also appreciably different according to the coenzyme specificity, while the Km values for NAD and NADP are quite similar. Finally, the growth of the cells on gamma-aminobutyrate as the sole source of nitrogen resulted in enhanced level of the NAD-dependent succinate-semialdehyde dehydrogenase, with concurrent decrease of the alternate enzyme activity. On the basis of the above results, distinct metabolic roles are suggested for the two enzymes forms.