Stephen Lortat-Jacob

Neonatal short bowel syndrome

In this retrospective study the management of infants who had undergone resection of more than 50% of the small bowel as newborn infants between 1970 and 1988 was analyzed to define prognostic factors. Small bowel resections were performed for atresia (36 cases), volvulus (22 cases), gastroschisis (10 cases), necrotizing enterocolitis (11 cases), and other disorders (8 cases). Patients were classified into two groups depending on the length of residual small bowel: group 1 (n = 35) had less than 40 cm of small bowel and group 2 (n = 51) had 40 to 80 cm of residual small bowel. Patients in group 2 had significantly better survival rates than those in group 1 (92.0% vs 66.6%; p less than 0.001). The patients in group 1 who were born after 1980, when home parenteral nutrition was introduced, had better survival rates than those who were treated before 1980 (95.0% vs 65.0%; p less than 0.01). The time required for acquisition of intestinal adaptation depended on the intestinal length (average, 27.3 months for group 1 and 14 months for group 2; p less than 0.01) and on the presence or absence of the ileocecal valve. Parenteral or supportive enteral nutrition, or both, ensured normal growth in both groups. We conclude that more than 90% of infants now survive after extensive small bowel resection with parenteral nutrition and that the remaining small intestine will adapt with time. Home-based parenteral nutrition allowed children to be treated in the best psychosocial environment.

A minority of 46,XX true hermaphrodites are positive for the Y-DNA sequence including SRY

SummaryA total of 30 cases of 46,XX true hermaphroditism was analysed for Y-DNA sequences including the recently cloned gene for male testis-determination SRY. In 3 cases, a portion of the Y chromosome including SRY was present and, in 2 cases, was localised, to Xp22 by in situ hybridisation. Since previous studies have shown that the majority of XX males are generated by an X-Y chromosomal interchange, the Xp22 position of the Yp material suggests that certain cases of hermaphroditism can arise by the same meiotic event. The phenotype in the 3 SRY-positive cases may be caused by X-inactivation resulting in somatic mosaicism of testis-determining factor expression giving rise to both testicular and ovarian tissues. Autosomal or X-linked mutation(s) elsewhere in the sex-determining pathway may explain the phenotype observed in the remaining 27 SRY-negative cases.

TRUE HERMAPHRODITISM : GENETIC VARIANTS AND CLINICAL MANAGEMENT

The diagnosis and management of 22 patients with true hermaphroditism are described. Sixteen of them were first seen before the age of 4 months. The initial manifestations were ambiguous genitalia in 20 cases (two of them identified prenatally by ultrasound examination), isolated clitoromegaly in one, and penile hypospadias plus unilateral cryptorchidism in one. All patients but one had at least one palpable gonad. Eleven of the twelve patients examined before the age of 6 months had basal plasma testosterone levels > 0.4 ng/ml. In older patients the stimulation test was necessary to demonstrate male testosterone secretion. The most common peripheral karyotype was 46,XX (17 cases); the other karyotypes were 47,XXY (1 case) and mosaicism 46,XX/46,XY (2 cases) or 46,XX/47,XXY (2 cases). One of the patients with the 46,XX karyotype had 46,XX/46,XY on fibroblast culture; four had the SRY gene in their leukocytes and one in the tissue taken at gonadal biopsy. A vagina was found in all patients at laparotomy, and a uterus was found in 17 cases (as a hemiuterus in 9). Genitography failed to demonstrate a uterus in only one case. The testicular tissue was dysgenetic but the ovarian tissue was normal. Sex assignment was male in 8 patients (reoriented by us in 2) and female in 14 patients (reoriented by us in 3). Spontaneous pubertal development occurred in the 4 patients (2 boys, 2 girls) with gonadal tissue who reached pubertal age. We conclude that true hermaphroditism is a heterogeneous condition in terms of its genetic background, with a prevalence of the 46,XX karyotype. There may be mosaicism with a Y-bearing cell line limited to the gonad (its frequency is probably underestimated), a paternal meiotic exchange between X and Y occurring in 46,XX cases with SRY, or a lack of the SRY gene, suggesting that other genes working independently of SRY may also determine testicular differentiation.

Quality of life and continence in patients with spina bifida

Purpose:Spina bifida (SB) is the most common congenital cause of incontinence in childhood. This study attempts to determine the relationships between urinary/faecal incontinence, methods of management, and Health Related Quality of Life (HRQoL) in people with SB.Patients and method:A total of 460 patients (300 adults and 160 adolescents) from six centres in France have taken part in this cross-sectional study. Clinical outcome measures included walking ability, urinary/faecal continence, and medical management. HRQoL was assessed using the SF36 in adults and the VSP in adolescents and their parents. Univariate and multivariate analysis was used to determine the relationships between clinical parameters and HRQoL.Results:HRQoL were significantly lower than in the general population. Adult women had significantly lower scores than men, and adolescent females had significantly lower scores for psychological well being. We did not found strong relationship between incontinence and HRQoL in this population. Moreover patients surgically managed for urinary/fecal incontinence did not show significantly higher scores of HRQoL.Conclusion:Using generic HRQoL measures, urinary/faecal incontinence and their medical management may not play a determinant role in HRQoL of persons with SB. However many other factors affect HRQoL in these patients. A longitudinal study design is recommended to assess whether incontinence management is associated with improve HRQoL.

Home parenteral nutrition in children: 8 years of experience with 112 patients.

It is essential that children on prolonged parenteral nutrition for anatomical or functional loss of small bowel should enjoy a quality of life which is as normal as possible. Their return home is a major factor in this. Over the past 8 years, 112 children were able to remain at home on cyclic parenteral nutrition. Forty-nine of them are no longer on home parenteral nutrition (HPN), 45 are still on HPN, and 18 have died. Growth and quality of life were good in most cases. Most of the complications were from infection, 1 septicaemia per 594 days on HPN. In the light of these results, HPN seems to be the best option for children requiring prolonged parenteral nutrition, although it can only be considered within the framework of a specialized centre, which ensures patient follow-up, and provides the logistical support required for this high-technology treatment.

Keyhole sign: how specific is it for the diagnosis of posterior urethral valves?

Posterior urethral valves (PUV) are the most common cause of renal impairment in boys during early childhood. Although antenatal suspicion of this pathology has become quite common in recent years, prenatal diagnosis remains challenging. The aim of this study was to evaluate the predictive value of different ultrasound criteria currently used to diagnose PUV.

Preservation of gonadal function in true hermaphroditism

Twelve documented cases of true hermaphroditism have been studied since 1965; there was histological evidence of both ovarian and testicular tissue in all cases. The clinical, anatomical, and therapeutic procedures are reviewedwith special emphasis on gonadal morphology, histology, and function. Seven patients were reared as females, 5 as males; 6 are now postpubertal and 3 are more than 30 years old. Five underwent bilateral castration; in seven cases, only the discordant gonadal tissue has been removed so that these patients may have endogenous gonadal secretion in keeping with their sex of rearing.

Long-Term Followup and Comparison Between Genotype and Phenotype in 29 Cases of Complete Androgen Insensitivity Syndrome

PURPOSE Diagnosis and management of the complete androgen insensitivity syndrome have dramatically changed in the last few decades, with earlier diagnosis and the development of molecular biology. Some phenotypic features such as development of wolffian and mullerian remnants have been suggested to be an index of subtle residual androgen activity. Variations of these features clearly exist among patients and may influence treatment. Our aim was to assess the safety of keeping gonads in place for spontaneous puberty in a cohort of patients with genetically proved complete androgen insensitivity syndrome. In parallel to the risks of virilization at puberty and gonadal tumor some additional features, such as need for vaginal surgery, were investigated. MATERIALS AND METHODS We studied the genotype, phenotype, anatomy of the internal and external genitalia, and clinical outcome of 29 cases of complete androgen insensitivity syndrome, managed by the same team from diagnosis (frequently in early childhood) to adulthood. RESULTS All patients had a complete female phenotype. A total of 19 different mutations (including 7 unreported) were found. Each family presented with a different mutation. No somatic mosaicism was detected. Vas deferens and epididymis were found in all types of mutations (missense, nonsense and frameshift). Of the patients 23 were postpubertal (19 spontaneously). No postpubertal virilization occurred. Only 1 carcinoma in situ was detected (postpubertally). Vaginal surgery was rarely necessary. CONCLUSIONS Our data advocate for keeping the gonads in the complete androgen insensitivity syndrome, at least until completion of spontaneous puberty. The risk of virilization at puberty should be ruled out for each androgen receptor mutation before management decisions and genetic counseling. Vaginal surgery should not be indicated as first line treatment.

A Multicenter Evaluation of Urinary Incontinence Management and Outcome in Spina Bifida

PURPOSE We describe urinary continence management and outcome in patients with spina bifida to identify the procedures that are most successful. MATERIALS AND METHODS In a multicenter retrospective cohort study medical charts were studied. At the same time in a cross-sectional survey sociodemographic characteristics, orthopedic features and urinary continence were described based on the frequency of leakage from the viewpoint of patients or close relatives using a Likert scale of 5 items, namely 1-leakage permanent to 5-leakage never. RESULTS A total of 421 patients were included, of whom 191 (45%) had been medically treated with a normal voiding pattern according to the patient viewpoint in 21%, clean intermittent catheterization in 61% and no specific bladder emptying method in 18%. The mean leakage score +/- SD was 2.74 +/- 1.55. On the other hand, 230 patients (55%) were surgically treated. Except for 23 patients who underwent noncontinent urinary diversion 207 were considered for treatment and continence description. The mean leakage score was 3.45 +/- 1.60. An artificial urinary sphincter in male and females, and a sling or Kropp technique in females were satisfactory when bladder enlargement was not required. In cases of bladder augmentation without continent diversion an artificial urinary sphincter in males and a bladder neck sling or cinch, Kropp and Young-Dees procedures in females have provided the best results. In cases of bladder enlargement with continent urinary diversion bladder neck closure or a wrap have provided the best results whatever the patient sex. CONCLUSIONS Many factors may influence the choice of a technique, such as patient sex, bladder characteristics or orthopedic conditions. However, since to our knowledge no randomized, controlled study has been yet performed, definitive conclusions on the best way to achieve urinary continence in patients with spina bifida cannot be established.

Long-term effects of dextranomer endoscopic injections for the treatment of urinary incontinence : An update of a prospective study of 61 patients

PURPOSE A prospective study was initiated 7 years previously to assess the efficacy of endoscopic dextranomer based implants for pediatric structural incontinence. Preliminary results revealed that at 3 years 50% of the patients were either dry or significantly improved. We report long-term results in the same cohort of patients. MATERIALS AND METHODS A total of 33 children and adolescents 5 to 18 years old with severe incontinence due to sphincteric incompetence (exstrophy-epispadias complex in 13, neuropathic bladder in 16, bilateral ectopic ureter in 4) were enrolled. Of the patients 13 underwent 2 and 4 underwent 3 treatment sessions to achieve a definitive result. Mean injected volume was 3.9 ml (range 1.6 to 12) per session. At each evaluation patients were considered cured (dryness interval 4 hours), significantly improved (minimal incontinence requiring no more than 1 pad daily and no further treatment required) or treatment failures (no significant improvement). Videourodynamics were used to study the evolution of the bladder capacity, activity and compliance. A total of 31 patients were followed 3 to 7 years after the last injection. RESULTS At 3 years after treatment 15 of 30 patients (50%) were dry or improved. One patient who had leakage after 3 years of dryness due to bladder deterioration subsequently underwent ileocystoplasty. At 4 years 12 of 25 patients (48%) were dry or improved. At 5 years 9 of 21 patients (43%) were dry, as were 4 of 11 (36%) at 6 years and 2 of 5 (40%) at 7 years of followup. The success rate according to pathological evaluation was comparable in neuropathic bladders (7 of 14, or 50%), exstrophy (3 of 6, or 50%) and epispadias (3 of 7, or 43%). Of 12 patients who underwent bladder neck plasty before the injection of bulking agent 7 (58%) were either dry or improved. The success rate was higher in males (13 of 23, or 57%) than in females (3 of 8, or 38%). Also, at puberty 2 males who were improved became dry. Bladder capacity increased in 12 of 18 initially small bladders and remained normal and stable in 9, while 4 initially dry patients had development of recurrent leakage secondary to bladder deterioration and underwent augmentation. Otherwise, there were no long-term side effects observed related to the injection of the bulking agent. CONCLUSIONS Endoscopic treatment of severe organic urinary incontinence with dextranomer is durable for up to 7 years of followup in 40% of the patients.