Abstract: ABSTRACT: Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma . The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities.
Abstract: SPRY2 is an inducible inhibitor of signalling mediated by tyrosine kinases receptors, whose targeting causes intestinal hyperganglionosis in mice. In this light, we have undertaken a mutational analysis of the SPRY2 gene in patients affected with intestinal neuronal dysplasia (IND), without detecting nucleotide changes in any of the 26 DNA samples analysed, with the exception of two already known polymorphic variants. A role of the SPRY2 gene in IND pathogenesis can be thus excluded.
Abstract: We report an unusual presentation of the P wave and QRS complex during ECG-guided endocavitary assessment of the proper location of the central venous catheter in a pre-term infant operated on for esophageal atresia. The P wave and QRS complex had a normal morphology, but lay specularly to normal above the isoelectric line. The chest x-ray showed that the unusual ECG pattern was due to the left paracardiac position of the catheter, just lateral to the aortic arch within a persistent left superior vena cava.
Abstract: Long-term results after surgical treatment of Hirschsprung disease (HSCR) are not always as good as a surgeon may perceive. Several studies have tried to correlate preoperative features to the surgical outcome of HSCR, but none came to definitive conclusions. Our study is aimed at identifying risk factors of poorer long-term outcome after surgery for HSCR.
Abstract: Although Hirschsprung's disease is curable, a low mortality and a certain morbidity have been described by several authors. We will present our experience with the treatment of Hirschsprung's disease at Gaslini Children's Hospital. All patients who underwent a pull-through procedure since January 1993 were included. Data were obtained from a comprehensive questionnaire and from the revision of the notes. The results were subsequently described and compared with regard to age and length of aganglionosis. A total of 151 patients underwent a pull-through. One hundred and twelve of these patients completed the forms and were reviewed. Eighty patients had a classic form, 22 an ultralong. Complications occurred in 28 patients (25%). Postoperative enterocolitis was complained by 25 patients (13% colonic and 59% ultralong forms) and constipation by 15 (equally distributed). Excellent to good continence was experienced by 84% of patients with classic forms and by 68% of patients with ultralong forms. A clear improving trend during growth was evident for patients with ultralong forms. Psychological self-acceptance, patients' perspective and cosmetic results proved to be significantly better for patients with classic forms of the disease. Our study confirmed the complications and long-term sequelae that patients with Hirschsprung's can experience. Early diagnosis can minimise morbidity and mortality and prompt and adequate treatment can reduce the incidence of postoperative complications. The parents should be acknowledged regarding the progressive improvements of function that patients gain during growth, particularly in case of ultralong forms, thus strengthening the need for continuative care and close follow-up.
Abstract: The diagnosis of Hirschsprung's disease (HSCR) should take place early in the neonatal period, because without an effective diagnosis and appropriate treatment, a considerable proportion of infants will go on to develop serious complications such as acute enterocolitis or toxic megacolon. Because no more than 10 % of HSCR cases have a late presentation with classical chronic constipation and megacolon, the clinician has to make a difficult, early diagnosis, which is the crux of the clinical problem. The aim of this review paper is to present all tools currently available to make a clear HSCR diagnosis and to discuss the problems facing the clinician and the pediatric surgeon in the correct identification of HSCR and of other intestinal dysganglionoses.
Abstract: The development of laparoscopic surgery has extended its uses to include adrenalectomy in children and in adults. Because conventional adrenalectomy requires a large incision, minimally invasive surgery offers a less aggressive solution in some selected cases. Twenty-nine adrenal masses in 26 children were treated using adrenalectomy between 1994 and 2004 (12 were treated laparoscopically, the remaining 17 with open surgery). Minimally invasive procedures were limited to the removal of small localized adrenal tumors and to biopsies. Although this approach must be limited to operations on lesions presumed to be benign, preoperative criteria for nonmalignancy are often difficult to define. Indications can be expanded to include to stage I neuroblastoma. There seems to be no age and weight limit. The technique applied varies in accordance with anatomy and the surgeon's experience: minimally invasive adrenalectomy, in our experience, was preferentially performed through a lateral retroperitoneal approach. Laparoscopic adrenalectomy can be used if the selection of cases is rigorous and the operations are performed by well-trained laparoscopic surgeons.
Abstract: The proto-oncogene RET is the major gene responsible for Hirschsprung's disease (HSCR), with RET mutations also implied in different pathologies. A variety of mutations of the RET proto-oncogene have been detected in HSCR patients. Special attention should be paid to rare patients who carry mutations of one of the critical cysteine residues of these exons, known to predispose to MEN2A. In these cases, HSCR can be associated with the development of neuroendocrine tumors such as medullary thyroid carcinoma (MTC) or MEN2A, for which a prophylactic thyroidectomy is advisable in the presence of a tumor causing RET mutation. In combined MEN2A/HSCR families, RET gene testing, tumor screening and prophylactic thyroidectomy are indicated as in MEN2A. The multigenic origin of HSCR and the absence of a "standard" RET mutation associated with HSCR currently make a routine molecular diagnosis impossible.
Abstract: Neural crest (NC) cells differentiate IN VITRO into neuroblasts, precursors of the enteric nervous system (ENS), when stimulated by specific agents. We developed a study aimed at establishing whether NC-derived neuroblasts can survive and colonise IN VIVO when injected into a recipient mouse gut.
Abstract: The RET proto-oncogene is the major gene involved in the complex genetics of Hirschsprung disease (HSCR), or aganglionic megacolon, showing causative loss-of-function mutations in 15-30% of the sporadic cases. Several RET polymorphisms and haplotypes have been described in association with the disease, suggesting a role for this gene in HSCR predisposition, also in the absence of mutations in the coding region. Finally, the presence of a functional variant in intron 1 has repeatedly been proposed to explain such findings. Here we report a case-control study conducted on 97 Italian HSCR sporadic patients and 85 population matched controls, using 13 RET polymorphisms distributed throughout the gene, from the basal promoter to the 3'UTR. Linkage disequilibrium and haplotype analyses have shown increased recombination between the 5' and 3' portions of the gene and an over-representation, in the cases studied, of two haplotypes sharing a common allelic combination that extends from the promoter up to intron 5. We propose that these two disease-associated haplotypes derive from a single founding locus, extending up to intron 19 and successively rearranged in correspondence with a high recombination rate region located between the proximal and distal portions of the gene. Our results suggests the possibility that a common HSCR predisposing variant, in linkage disequilibrium with such haplotypes, is located further downstream than the previously suggested interval encompassing intron 1.
Abstract: Caudal regression syndrome (CRS) is a congenital heterogeneous constellation of caudal anomalies that include varying degrees of agenesis of the spinal column, anorectal malformations (ARMs), genitourinary anomalies, and pulmonary hypoplasia. The combination of a particular form of hemisacrum, ARM, and presacral mass (teratoma, anterior meningocele, rectal duplication, or a combination thereof) constitutes Currarino syndrome (CS). Previous reports have shown HLXB9 to be a major causative gene for CS. The aim of our study was to reevaluate the involvement of the HLXB9 gene in a larger group of CRS cases.
Abstract: Since Noblett (J Pediatr Surg 1969;4:406-409) described her innovative tool, rectal suction biopsy (RSB) has become the gold standard in the diagnosis of Hirschsprung's disease and other intestinal dysganglionoses. Many different instruments have been developed during the last 30 years, but none of them proved to be free of disadvantages. In 2000, at Gaslini Research Institute, we developed an improved tool to perform RSBs called Solo-RBT (SAMO Biomedica, Bologna, Italy), which has some advantages: (1) the procedure is easily performed by one operator alone; (2) the instrument can be adjusted for each patient according to age and weight; and (3) the instrument can be completely disassembled for decontamination and heat sterilization. This study describes our experience with Solo-RBT in the diagnosis of intestinal dysganglionoses.
Abstract: X-linked alpha thalassemia mental retardation (ATR-X) syndrome is associated with profound developmental delay, facial dysmorphism, genital abnormalities, and alpha thalassemia. Patients with ATR-X syndrome frequently present with gastrointestinal problems, in particular feeding difficulties, regurgitation and vomiting, abdominal pain, distension, and chronic constipation. Parental reports of prolonged food refusal and distress in these children are common and although these episodes are suspected to be gastro-intestinal in origin they are rarely investigated. Death in early childhood from aspiration of vomitus or from pneumonia presumed to be secondary to aspiration has been recorded in a number of ATR-X cases. In this report we review the gastrointestinal phenotype of ATR-X syndrome in 128 cases. We also demonstrate that in two siblings, regurgitation was secondary to gastric pseudo-volvulus, a condition in which the stomach does not have a normal system of peritoneal ligaments and changes position with possible torsion around itself. Furthermore, ultra-short Hirschsprung disease with colonic hypoganglionosis was shown and this may contribute to the severe constipation affecting these children.
Abstract: Anorectal malformations (ARM) are common congenital anomalies seen throughout the world. Comparison of outcome data has been hindered because of confusion related to classification and assessment systems.
Abstract: Intestinal Dysganglionoses (IDs) represent a heterogeneous group of Enteric Nervous System anomalies including Hirschsprung's disease (HD), Intestinal Neuronal Dysplasia (IND), Internal Anal Sphincter Neurogenic Achalasia (IASNA) and Hypoganglionosis. At present HD is the only recognised clinico-pathological entity, whereas the others are not yet worldwide accepted and diagnosed. This report describes the areas of agreement and disagreement regarding definition, diagnosis, and management of IDs as discussed at the workshop of the fourth International Meeting on "Hirschsprung's disease and related neurochristopathies." The gold standards in the preoperative diagnosis of IDs are described, enlighting the importance of rectal suction biopsy in the diagnostic workup. The most important diagnostic features of HD are the combination of hypertrophic nerve trunks and aganglionosis in adequate specimens. Acetylcholinesterase staining is the best diagnostic technique to demonstrate hypertrophic nerve trunks in lamina propia mucosae, but many pathologist from different centers still use H&E staining effectively. Moreover, the importance of an adequate intraoperative pathological evaluation of the extent of IDs to avoid postoperative complications is stressed. Although it is not clear whether IND is a separate entity or some sort of secondary acquired condition, it is concluded that both IND and IASNA do exist. Other interesting conclusions are provided as well as detailed results of the discussion. Further investigation is needed to resolve the many controversies concerning IDs. The fourth International Conference in Sestri Levante stimulated discussion regarding these entities and led to the International guidelines to serve the best interest of our patients.
Abstract: The spontaneous mouse mutant Dominant megacolon (Dom) represents the model of the Waardenburg-Hirschsprung's disease, a syndromic pathology, characterized by the association of pigmentation defects (PD), deafness, and Hirschsprung's disease (HD). The defect in Dom mouse is caused by a spontaneous mutation of the gene encoding the Sry-related transcription factor Sox10. This mutation affects several aspects of neural crest development leading to combined enteric innervation and pigmentation defects, both in mouse and human. The purpose of this report is to define, by enzymo-histochemical techniques routinely used for the diagnosis of human Hirschsprung's disease (AChE, LDH, NADPH-diaphorase), the innervative patterns of the affected gut.
Abstract: The authors analyzed the results of a modified entirely mechanical Duhamel pull-through for the treatment of Hirschsprung' disease or type B intestinal neuronal dysplasia. The aim of the follow-up was to evaluate results of a Duhamel procedure entirely performed with the use of staplers.
Abstract: The Currarino syndrome (CS) is a peculiar form of caudal regression syndrome (CRS) characterized by the association of hemisacrum, anorectal malformation (ARM), and presacral mass. The authors analyzed retrospectively their series, and they propose a multidisciplinary diagnostic and therapuetic protocol that until now has not been introduced.
Abstract: Perineal sagittal approaches (posterior sagittal anorectoplasty and anterior and posterior sagittal transanorectal approaches) allow complete anatomic exposure of the perineum and lower pelvis. Moreover, they reduce the risk of damaging important structures because the incision is led in the midline. Therefore, many surgeons have used these approaches to treat diseases other than anorectal malformations (ARM), including intestinal dysganglionosis, trauma, pseudohermaphroditism, presacral mass, and rectal duplication. The aim of this study was to describe a small series of patients operated on via these approaches at Gaslini Children's Hospital over a 5-year period. We retrospectively evaluated 10 patients consecutively operated on via a perineal sagittal approach, with or without sphincteric structure involvement, between January 1997 and December 2001. All of these patients were without ARM. Indications included retrorectal abscesses (two), iatrogenic anal canal stenosis (one), postinflammatory anal canal stenosis (one), internal anal sphincter neurogenic achalasia (one), female pseudohermaphroditism (one), benign sacrococcygeal teratomas (two), malignant sacrococcygeal teratoma (one), and perineal rhabdomyosarcoma (one). Protective colostomy was used in four patients. The parameters that we analysed included technical details, possible complications, perineal cosmetic appearance, and outcome. No complications were experienced. The postoperative cosmetic perineal appearance was excellent in all patients, and continence, when assessed, was always considered satisfactory. All tumours underwent complete gross resection. However, one patient with malignant sacrococcygeal teratoma died as a result of the malignant process 2 years after surgery. Although our study was carried out on a small series of patients, it confirmed that perineal sagittal approaches can be used not only for ARM but also for other conditions involving perirectal pouches, presacral space, and urogenital structures, as these approaches are safe and provide excellent cosmetic results as well as satisfactory functional outcome. Although tumours can be treated via these approaches, outcome remains related to the nature and malignancy of the disease itself.
Abstract: Intestinal neuronal dysplasia (IND) is a complex alteration of the enteric nervous system (ENS) that may involve rectum, colon, or the whole intestine. This disorder is a frequent cause of intestinal dysmotility and pseudo-obstruction in the first 3 years of life. The aim of this study was to identify possible associations and correlations of IND with other gastrointestinal and nongastrointestinal anomalies.
Abstract: Intestinal Neuronal Dysplasia (IND) is a congenital disorder characterized by intestinal motility defects associated with hyperplasia of enteric ganglia. A phenotype resembling human IND has been observed in mice knocked-out for a member of the Hox11 homeobox gene family, Hox11l1, suggesting that the human homologue of this gene could be responsible for congenital disorders of intestinal innervation. However, previous mutation analysis of the coding sequence of the HOX11L1 gene in patients affected with IND detected neither mutations nor other nucleotide variants. In the present work, a detailed study of the non coding promoter region of this gene was undertaken in patients affected with IND, with Hirschsprung associated IND and with neurogenic chronic intestinal pseudo-obstruction. No alterations potentially impairing expression of HOX11L1, such as nucleotide variants, small deletions or cytogenetic alterations, could be identified thus further excluding the direct involvement of this gene in the pathogenesis of human intestinal motility disorders.
Abstract: Multiple endocrine neoplasia (MEN) 2B is a hereditary syndrome including medullary thyroid carcinoma (MTC), pheochromocytoma, gastrointestinal (GI) disorders, marfanoid facies, and multiple ganglioneuromas. MTC is the major cause of mortality, and often appears during the 1st decade of life. RET proto-oncogene mutations are responsible for MEN 2B. Other RET mutations cause MEN 2A syndrome, familial MTC, or Hirschsprung's disease. We studied three MEN 2B patients with the aim of delineating the best diagnostic and therapeutic protocol. The gold standards for diagnosis are histochemical study of the rectal mucosa and molecular analysis of RET, which in familial cases detects MEN 2B at a preclinical stage so that early total prophylactic thyroidectomy can be performed. In non-familial cases, the diagnosis can be suggested by the presence of GI symptoms, ganglioneuromas, and/or the typical facies. The intestinal innervation pattern, analyzed with the acetylcholinesterase technique, is pathognomonic for MEN 2B. In our protocol a rectal biopsy is, therefore, the first measure. The surgical treatment of MEN 2B is total thyroidectomy with cervical lymphadenectomy of the central compartment of the neck. When possible, this intervention should be performed prophylactically before 1 year of age.
Abstract: Peritoneal adhesions (PA) represent a major cause of morbidity in pediatric surgical patients. The pathogenesis is still largely unknown. A possible role could be played by foreign bodies (FB) accidentally contaminating the operative field during surgery. We report a histologic study of PA in a rat model and in children, investigating the role of FB in their formation. Abdominal adhesions were studied in 18 rats. In 6 (group A) we performed a laparotomy and rubbed the visceral and parietal peritoneum with a cotton bud. In 6 (group B) we performed a minimal laparotomy and injected powdered autologous and heterologous material into the peritoneal cavity, avoiding any peritoneal abrasions. In 6 (group C) we performed a laparotomy and applied both treatment methods, i.e., rubbing and injection of FB. After 1 month, at autopsy rats were classified according to the presence and grade of surgical adhesions. Twenty-two PA were also collected from seven children undergoing abdominal surgery in whom one or more procedures had been previously performed. The adhesions were stained with hematoxylin-eosin and Giemsa stains for histologic examination. Adhesions were found in 4 rats of group A and all 6 rats of group C. None were identified in group B. Group C rats showed a higher grade of adhesions with respect to group A. In both humans and animals PA were always found to coexist with microscopic particles of solid substances, which were incorporated inside the connective tissue. However, after simple injection of FB into the abdominal cavity we did not observe any PA. These data suggest that two different stimuli are necessary for adhesion formation: a direct lesion of the mesothelial layers and a solid substrate (FB). We underline the importance of reducing contamination with FB during surgery. On the basis of these considerations, the laparoscopic approach seems to be particularly pertinent.
Abstract: Aim of this study was to investigate, for the first time, whether isolated newborn mouse enteric plexus could induce in vitro differentiation of the vagal neural crest-derived cells into enteric neuroblasts. Fragments of the myenteric plexus were isolated from the small intestine of 6-day-old Swiss mice and were collected and stored in DMEM-F12 medium, then cultured on polymerized human fibronectin layer. The vagal portion of the neural tube, isolated from a 9.5-day-old Swiss mouse embryo, was put in the same chamber slides where the isolated myenteric plexus had been cultured for 3 days. The vagal neural crest-derived cells migrated onto the polymerized human fibronectin layer and formed a crown of cells around the neural tube. After 6 days, the cultures were stopped and studied immunohistochemically for anti-NF160 KD, anti-TH, and RetR5 antibodies to analyse the differentiation stage of the cultured cells. Analysis of results included the comparison of two culture groups: Group 1, used as control, in which vagal neural crest-derived cells were put in DMEM-F12, supplemented only with 10 % of FCS; Group 2, in which vagal neural crest-derived cells were put in the same medium as Group 1, with the addition of myenteric plexus fragments isolated from newborn mice to form the co-culture. The following results were obtained: in Group 1 the neural tubes originated a cell population strongly positive for anti-NF160 and anti-TH Ab, but negative for RetR5 Ab. This positivity was found both in the cells adjacent to the neural tube and in those migrating from it distally. The Group 2 originated cells, which after migration were positive for anti-NF160 and for anti-TH antibodies. In addition, in this culture group, the cells which migrated from the neural tube were positive for anti-RetR5 antibody. The co-culture used in this study induces the differentiation of vagal stem cells into enteric neuroblasts, cells TH+ and RetR5+. These cells, after reaching the embryonic intestine, migrate to colonize the hindgut and form the ENS. Therefore this biotechnology seems a good method to obtain in vitro enteric precursors of ENS.
Abstract: Preoperative histochemistry on rectal mucosal-submucosal specimens is the most important step in the diagnosis of Hirschsprung's disease and other dysganglionoses. Today, rectal mucosal-submucosal biopsy specimens are obtained by suction with the widely used tool first designed by Noblett in the late 1960s. The authors developed a new instrument, for which a patent has already been filed, for one-hand execution of rectal suction biopsies, which will make this operation easier and faster.
Abstract: The most commonly used acetylcholinesterase (AChE) method for the diagnosis of Hirschsprung's disease (HD) and intestinal neuronal dysplasia (IND) was first introduced in 1964 by Morris Karnovsky and Logan Roots. This technique requires about 80 - 120 minutes incubation time and cannot be used for the intraoperative diagnosis of HD and IND. To avoid these limitations, in 1994 Kobayashi et al first proposed an accelerated modified method in two different versions, the first using diaminobenzydine (DAB) reagent, the second using 4-chloro-1-naphthol as final reagent. In the present study, we propose a new rapid variation of AChE staining which avoids the use of DAB and naphthol, notably toxic reagents, but follows the same acceleration principle of Kobayashi's technique. Our modified rapid AChE requires a total incubation time of only 8 minutes, which is compatible with intraoperative histochemical examination purposes. Intraoperative seromuscular or full-thickness intestinal biopsies were obtained from 92 children affected by intestinal dysganglionoses. The biopsies were frozen and cut in 15 microm cryostatic sections. Rapid AChE was performed with a special incubation medium using 3-amino-9 ethylcarbazole (AEC) as chromogenic substance. The two complementary histochemical techniques alpha-naphthylesterase (ANE) and lactate-dehydrogenase (LDH) were also used intraoperatively for the staining of ganglion cells. The diagnosis was confirmed postoperatively with conventional AChE Karnovsky technique, comparing the extensions of hyperganglionic, hypoganglionic and aganglionic segments in each studied case. The new rapid AChE modified method can identify ganglion cells and fibers using a dark brown precipitate. In all the cases studied, the intestinal innervation pattern identified with this modified technique was similar to that obtained with Karnovsky AchE. Seventy-eight HD, 8 isolated IND and 6 HD associated with an evident IND segment were diagnosed. This new rapid AChE histochemical technique avoids the use of DAB and naphthol, and can thus be considered safe for operators. Rapid AChE is a valid tool for both the evaluation of aganglionosis extension and for the identification of IND pattern during surgery. We recommend this very reliable method for the intraoperative diagnosis of HD and IND, in association with other enzymatic markers of ganglion cells (ANE or LDH). We propose the following diagnostic protocols: a) for preoperative histochemical study: conventional AChE plus LDH and NADPH-diaphorase; b) for intraoperative study: rapid AChE plus ANE.
Abstract: The sacral ratio (SR) was proposed by Alberto Peña in 1995 as a reliable tool to evaluate sacral development in anorectal malformations (ARM). The SR is obtained by comparing sacrum size with fixed bony parameters of the pelvis. In previous studies, the average normal SR was calculated to be 0.74 for the anteroposterior view (APSR) and 0.77 for the lateral view (LSR).
Abstract: Hirschsprung's disease is an inherited disorder showing incomplete penetrance and variable expressivity. Genetic mapping and mutation screening of candidate genes, together with the study of several natural and knockout animal models, clearly have shown the involvement of several different genes in the pathogenesis of Hirschsprung's disease. Among these genes, the RET proto-oncogene accounts for the highest proportion of both familial and sporadic cases, with a wide range of mutations scattered along its entire coding region. The low detection rate of RET mutations in Hirschsprung patients also led to different hypotheses, such as the existence of additional Hirschsprung genes. Different animal and human genetic studies have identified 6 Hirschsprung genes: RET proto-oncogene (RET), endothelin 3 (EDN3), endothelin B receptor gene (EDNRB), glial-cell-line-derived neurotrophic factor (GDNF), endothelin converting enzyme (ECE1), gene encoding the Sry-related transcription factor SOX10 (SOX10). Microenvironmental factors also can play a role in the pathogenesis of aganglionosis. The developmental process of the crest-derived progenitor cells is sensitive to the level of different molecules. The expression deficit of different factors (GDNF, NTN) in the hindgut, in the absence of genetic mutations, could determine a missed activation of the receptor system, causing enteric neuroblast migration arrest.
Abstract: The posterior sagittal anorectoplasty (PSARP) is widely recognized as the best technique available today for the surgical treatment of anorectal malformations (ARM). However, different retrospective studies on the functional results of PSARP in the treatment of ARM have shown different postoperative degrees of constipation. In particular, even in patients with normal sacrum, about 70% of operated ARM with vestibular fistula and about 50% with perineal fistula can be complicated by fecal constipation and pseudoincontinence. In order to identify preoperatively whether ARM patients present abnormal innervation patterns of rectal pouch and fistula (as reported by Holschneider et al [7]), we decided to study suction rectal biopsies performed by introducing SBT-100 rectal suction biopsy tool into the fistula at 6, 4, 3 and 2 cm from the meatus. To date, this approach has been adopted in 22 ARM cases (15 females and 7 males, age range 7 days-4 years), 6 of them with recto-vestibular fistula and 13 with recto-perineal fistula. Biopsies were frozen in isopentane at liquid nitrogen temperature and cryostatic sections were studied by acetylcholinesterase (AChE), succinic-dehydrogenase (SDH) and alpha-naphthyl-esterase (ANE) enzymo-histochemical techniques. The results concerning the innervation-type of fistula and proximal rectal pouch were confirmed by the biopsies obtained during PSARP. Our overall incidence of rectal innervation intrinsic disorders was 81.82%. In particular, all our cases of vestibular fistula presented associated dysganglionoses. The incidence of associated Hirschsprung's disease was high, corresponding to 18% of cases. Our results suggest that the high frequency of constipation in low forms of ARMS depends on primary intestinal neuronal malformations and it cannot be ascribed to a denervation secondary to rectal dissection and to PSARP procedure. We propose the introduction of this type of preoperative enzymo-histochemical diagnosis in ARM cases because it can select those patients with severe associated dysganglionoses. In our opinion, if this diagnosis is available preoperatively, PSARP can be performed without using abnormally innervated structures and reducing postoperative functional complications.
Abstract: This paper reports the case of an infant born with type I esophageal atresia (EA) associated with duodenal atresia (DA). The critical condition of the patient necessitated an exploratory laparotomy, which revealed severe dilatation of the stomach and duodenum. The routine procedure for repairing type I EA is a delayed primary anastomosis after 10 weeks of age because of the long gap between the two esophageal segments. In our case, due to the concomitant DA, the lower pouch was long enough to allow primary neonatal anastomosis. A radiograph taken with a Hegar dilator in the lower segment via the gastrostomy confirmed this suspicion, and the baby underwent a thoracotomy and primary anastomosis between the esophageal pouches. The authors propose the possibility of primary esophageal anastomosis in similar cases.
Abstract: Anorectal malformations (ARMs) are common congenital anomalies that account for 1:4 digestive malformations. ARM patients show different degrees of sacral hypodevelopment while the hemisacrum is characteristic of the Currarino syndrome (CS). Cases of CS present an association of ARM, hemisacrum and presacral mass. A gene responsible for CS has recently been mapped in 7q36. Among the genes localized in this critical region, sonic hedgehog (SHH) was thought to represent a candidate gene for CS as well as for ARM with different levels of sacral hypodevelopment according to its role in the differentiation of midline mesoderm. By linkage analysis we confirmed the critical region in one large family with recurrence of CS. In addition, the screening of SHH in 7 CS and in 15 sporadic ARM patients with sacral hypodevelopment allowed us to exclude its role in the pathogenesis of these disorders.
Abstract: The spontaneous mutant Danforth's short tail (Sd) mouse has been studied over the last 60 years from the morphological, embryological, and genetic point of view. The Sd mutation affects a gene essential to notochordal development, and the Sd mouse phenotype represents an analogue of human caudal regression syndrome. The Sd/Sd mouse presents different types of anorectal malformations (ARM) and was suggested as a simple and cheap model of investigation of ARM morphology and embryology. In the current study, the Sd mouse enteric nervous system (ENS) was thoroughly investigated with specific immunohistochemical markers.
Abstract: In a few patients with Hirschsprung disease (HSCR) and no clinical symptoms of multiple endocrine neoplasia type 2 (MEN-2A) or medullary thyroid carcinoma (MTC), missense mutations in the cysteine residues 609 and 620 of the Ret gene have been identified. In several pedigrees with either MEN-2A or familial MTC (FMTC) a documented germline mutation in cysteine 618 or 620 follows the segregation of the disease phenotype. The appearance of the HSCR phenotype in such patients and pedigrees cannot be easily reconciled with the gain of function which is associated with the dominant oncogenic effect of MEN-2A mutations. Gastrointestinal manifestations are known to occur also in association with MEN-2B but, to the best of our knowledge, in only very few cases the intestinal phenotype of MEN-2B has been investigated by enzymo-histochemical techniques, as in the present work. We report an extensive molecular study of patients, two with HSCR and FMTC carrying a Cys620Arg or Ser mutation and two with MEN-2B and gastrointestinal symptoms carrying a Met918Thr mutation. One of the latter two patients showed aganglionosis of the last 5 cm of rectum which caused a congenital megacolon leading to the diagnosis and operation for HSCR. The mutation screening of all the exons of Ret in 3 of these patients did not reveal any additional mutation. Therefore these results do not support the hypothesis of additional constitutional Ret mutations in patients showing association of MEN-2 and HSCR, whilst the histochemical and clinical data in one of these patients indicate that MEN-2B can be associated with a true form of short segment HSCR.
Abstract: In 1996, the glial cell line-derived neurotrophic factor (GDNF) was identified as one of the ligands of the RET transmembrane receptor. In the same year, GDNF mutations were found in association with RET protooncogene mutations in Hirschsprung patients. Mutations in GDNF per se are thought neither necessary nor sufficient to cause Hirschsprung's disease (HD). To date, our study group has identified GDNF mutations only in 2 of 98 cases of intestinal dysganglionosis. The aim of our study was to investigate a possible expression deficit of GDNF in the enteric nervous system of Hirschsprung patients not mutated for the GDNF gene.
Abstract: The authors describe the genetic, pathophysiology, diagnostic, and therapeutic aspects of total colonic aganglionosis and of aganglionosis extending to the small intestine. The pathogenesis of this disease is genetically determined and is related to the differentiation and migration of cells derived from neural crests. The clinical and radiological features can be useful in the diagnosis but they are not pathognomonic. The histochemical estimation of acetylcholinesterase activity in suction rectal biopsies is useful in establishing the diagnosis; however, the specimens should be examined by an experienced pathologist. The definitive diagnosis of either condition is obtained by performing intraoperative seromuscular biopsies of the rectum, colon, and ileum. From the therapeutic point of view, many surgical techniques have been proposed for the radical treatment of this disease. Some of the techniques have been derived from operations proposed for the treatment of classic Hirschsprung's disease; others have been specifically designed.
Abstract: Intestinal neuronal dysplasia (IND) belongs to the group of dysganglionosis. It may occur as part of a syndrome of early chronic constipation, neonatal intestinal occlusion, chronic intestinal pseudo obstruction. The aim of this study was to report the cases examined by the Istituto G. Gaslini in Genoa and to discuss the numerous aspects of this disease which are still unclear.
Abstract: Hirschsprung disease, or congenital aganglionic megacolon, is a genetic disorder of neural crest development affecting 1:5,000 newborns. Mutations in the RET proto-oncogene, repeatedly identified in the heterozygous state in both long- and short-segment Hirschsprung patients, lead to loss of both transforming and differentiating capacities of the activated RET through a dominant negative effect when expressed in appropriate cellular systems. The approach of single-strand conformational polymorphism analysis established for all the 20 exons of the RET proto-oncogene, and previously used to screen for point mutations in Hirschsprung patients allowed us to identify seven additional mutations among 39 sporadic and familial cases of Hirschsprung disease (detection rate 18%). This relatively low efficiency in detecting mutations of RET in Hirschsprung patients cannot be accounted by the hypothesis of genetic heterogeneity, which is not supported by the results of linkage analysis in the pedigrees analyzed so far. Almost 74% of the point mutations in our series, as well as in other patient series, were identified among long segment patients, who represented only 25% of our patient population. The finding of a C620R substitution in a patient affected with total colonic aganglionosis confirms the involvement of this mutation in the pathogenesis of different phenotypes (i.e., medullary thyroid carcinoma and Hirschsprung). Finally the R313Q mutation identified for the first time in homozygosity in a child born of consanguineous parents is associated with the most severe Hirschsprung phenotype (total colonic aganglionosis with small bowel involvement).
Abstract: Recent molecular-genetic and histochemical studies of intestinal aganglionosis have confirmed the initial classification established by Bolande, who considered Hirschsprung's disease (HD) a neurocristopathy. This paper is a critical review of the results of molecular-genetic studies carried out from 1992 to date. In particular, the author focuses on the possible clinical impact of the identification of RET as a causative gene for HD.
Abstract: Because the spectrum of anorectal malformations is wide, genetic investigations of these anomalies should include the study of multigenic models presenting variable penetrance and expressivity. Current knowledge in clinical genetics, cytogenetics, and molecular genetics of anorectal anomalies are reviewed. The analysis of associated anomalies (that are found in more than 60% of anorectal malformations) is an important aspect of the molecular study, because the association of anomalies with mendelian transmission or with a recognized causative gene can be an essential starting point for further investigations. In the present study, the authors focus on associated sacral anomalies, urethral malformations, and intestinal dysganglionoses. In particular, associated sacral anomalies could be a partial expression of the Currarino syndrome, which represents the only association for which genetic evidence has been demonstrated by linkage analysis. The authors studied a four-generation pedigree with recurrence of the Currarino syndrome, and the haplotype reconstruction confirmed that the gene segregating in this family is located in the 7q36 region. The collection and study of families with multiple cases of anorectal malformations could show whether different phenotypes are caused by single genes.
Abstract: Malformations of the front chest wall are congenital defects that have been reported since the seventeenth century and which include the clinical syndromes of funnel chest, pigeon chest and Poland's syndrome. Although they have been reported for such a long time, their pathogenesis is in many ways still unknown and the theories proposed up until now reveal uncertain and unsatisfactory findings. Attempts to gather precise information regarding their real incidence are equally ineffective given that frequently those cases which are not particularly severe are not referred for specialist care. These malformations usually involve severe psychological problems caused by the deformity and, in more severe cases, may lead to alterations in normal cardiac and respiratory function which are above all evident during intense physical effort.
Abstract: A major gene for Hirschsprung's disease (HD) recently has been mapped in chromosome 10q11.2 and identified to be the RET proto-oncogene. Mutations of the RET gene have occurred in HD patients, and abnormalities of expression and function of Ret protein (a receptor tyrosine kinase, which is the product of the RET gene) have been found in their intestines. In vitro studies of the biological effects of HD mutations suggest a loss of function effect, which may be negative-dominant. However, the developmental role of the Ret protein in the organogenesis of the enteric nervous system (ENS) and its role in the pathogenesis of HD remain unclear. The authors present a study of the expression of Ret protein in the human ENS during fetal development. Fresh rectal tissues were obtained from nine fetuses (gestational age range, 12 to 22 weeks). Ret protein expression was studied immunohistochemically, using antibodies against the carboxy-terminal 20 amino acids (anti-Ret C) and the extracellular domain (anti-Ret R5). The tyrosine kinase activity of the fetal ENS was investigated with antiphosphotyrosine mouse monoclonal antibody against the phosphorylated tyrosine residues. Anti-Ret C immunostaining was observed in ganglion cells at all ages, but intense activity was significantly higher among the cells of the younger fetuses. Intense anti-Ret R5 immunostaining was present in the enteric ganglion cells of the 12-week-old fetus. The tyrosine kinase activity of ganglion cells increases progressively with advancing gestational age. The results of this study support the hypothesis that the Ret protein receptor might play a crucial role in the cellular and molecular processes involved in the development and maturation of the ENS, abnormalities of which could result in HD. High Ret protein expression and low tyrosine kinase activity have been reported to occur in small ganglia of the HD hypoganglionic segment. In the present study, these markers were typical of the primitive and immature ENS during the early phase of hindgut development.
Abstract: A major gene causing Hirschsprung's disease was recently mapped in 10q11.2. Its physical localization was restricted to a 250-Kb interval containing the RET proto-oncogene (REarranged during Transfection). In 1994, point mutations affecting the RET proto-oncogene were identified in patients with Hirschsprung's disease. The authors present an immunohistochemical study on the expression and localization of the Ret protein (a receptor tyrosine kinase, which is the RET proto-oncogene product) in the intestinal plexuses of patients with Hirschsprung's disease. Ninety-two full-thickness intestinal wall pieces from 29 pediatric patients were studied (19 cases of classic Hirschsprung's disease, 5 of total colonic aganglionosis, and 5 controls). Ret protein immunohistochemical localization was obtained using c-Ret R5, anti-Ret K and anti-Ret C antibodies, respectively, against the extracellular domain, the tyrosine kinase domain, and the carboxy-terminal 20 amino acids of the Ret protein. A diffuse granular staining was present in the ganglia of normal colon, whereas the small ganglia of the hypoganglionic colon showed a reduced number of ganglion cells that were strongly stained with c-Ret R5 MoAb. A reduced synthesis of Ret protein was shown in the ganglionic and hypoganglionic segments of two cases of this series, the first with a complete deletion of the RET proto-oncogene and the second with a frameshift mutation and a stop codon in the extracellular domain. The activity of the receptor tyrosine kinases (RTKs) in intestinal ganglion cells was investigated using antiphosphotyrosine antibodies. A very low tyrosine kinase activity was shown in the small ganglia of the hypoganglionic segment.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The final aim of the treatment of oesophageal atresia is to restore continuity without the interposition of intestinal segments. The authors present the results of a new diagnostic method combining endoscopy and radiology to evaluate the development of pouches in oesophageal atresia. This new method has been successfully adopted in four patients aged between 4 and 8 months, three with type I and one with type III complicated atresia. Direct end-to-end anastomosis was performed in all patients. We think this method can be easily applied and is a suitable diagnostic examination in all cases in which surgical strategy aims at restoring oesophageal continuity by means of direct anastomosis.
Abstract: Anterior chest wall deformities in children are the expression of some congenital malformation such as Poland's syndrome and pectus excavatum. The surgical treatment of these malformations affecting children is aimed at correcting large wall defects and stabilizing the chest wall, assuring at the same time chest harmonious growth and postoperative functional assessment. We present the results of the treatment of 2 cases of Poland's syndrome, 20 cases of pectus excavatum and 2 cases of pectus carinatum, with a follow-up of 6 months--9 years.
Abstract: The authors present a review of 431 children biopsied and studied with the following histochemical and immunohistochemical techniques: 1) acetylcholinesterase activity; 2) alphanaphthylesterase activity; 3) S-100 protein immunohistochemical technique; 4) glyoxylic acid method. Two hundred forty-eight patients of our series presented different forms of dysganglionosis, 12 of them (4.8%) presenting neuronal intestinal dysplasia type B. In 7 cases, NID type B was diffuse, whereas in 5 recto-colonic NID type B was confined to the splenic flexure. Male:female ratio was 9:3. Familial recurrence was present in 2 of the 12 cases of our series, affected by severe neuronal intestinal dysplasia extended to the small intestine, associated with intestinal malrotation and short bowel syndrome. Four of the 7 cases of diffuse NID type B and 2 of the 5 cases of rectocolonic NID type B were surgically treated. Three patients with diffuse NID died from sepsis within the 2nd year of life. This study confirms that NID type B is a form of dysganglionosis which can be diagnosed in a Mediterranean country if histochemical techniques are applied in the study of a large series of constipated and pseudo-Hirschsprung patients. From a pathogenetic point of view, the authors compared the histochemical findings of biopsies from their series of NID patients with those of recto-colonic biopsies from patients with MEN II B syndrome. The similarity of GI symptoms in MEN II B and NID pediatric patients suggests that the two disorders could be the result of mutations affecting the same domain of the RET proto-oncogene.
Abstract: A cytogenetically detectable deletion, del(10) (q11.2-->q21.2), was observed in a patient with total colonic aganglionosis with small bowel involvement (TCSA), a variant of Hirschsprung disease (HSCR). A similar deletion is present in another TCSA patient (S.M. Huson, personal communication). To reveal cytogenetically undetectable deletions of chromosome 10 in further patients, we developed a strategy for mapping chromosome 10 DNA markers with respect to the observed deletions. To this end, the two chromosome 10 homologs (deleted and normal) were segregated in two distinct somatic cell hybrids obtained after fusion of the patient's fibroblasts with a Chinese hamster ovary cell line (YH21). Hybrid cells containing chromosome 10 were selected for the expression of the gene coding for the beta subunit of the fibronectin receptor (FNRB), which maps to 10p11.2, using a monoclonal antibody against FNRB. Hybrid 185.O contains the deleted chromosome, whereas hybrid 179.Q contains the nondeleted one. Southern blot and PCR analysis of DNA from these two hybrids mapped the markers RBP3H4, RET, D10S15, D10S5, D10S22, and D10S88 inside the deletion and D10S170, CDC2, EGR2, and D10S19 outside the deletion. MEN2A and MEN2B have recently been mapped within the centromeric region closely linked to RBP3 and D10S15 (which are located inside the deletion) and cosegregate with HSCR in at least two different pedigrees. Since HSCR, MEN2A, and MEN2B represent defects of neural crest cell development, we hypothesize that they originate from mutations in different genes clustered in the centromeric region of 10q.
Abstract: Hirschsprung disease (HSCR) is a frequent congenital disorder (1 in 5,000 newborns) of unknown origin characterized by the absence of parasympathetic intrinsic ganglion cells of the hindgut. Taking advantage of a proximal deletion of chromosome 10q (del 10q11.2-q21.2) in a patient with total colonic aganglionosis, and of a high-density genetic map of microsatellite DNA markers, we performed genetic linkage analysis in 15 non-syndromic long-segment and short-segment HSCR families. Multipoint linkage analysis indicated that the most likely location for a HSCR locus is between loci D10S208 and D10S196, suggesting that a dominant gene for HSCR maps to 10q11.2, a region to which other neural crest defects have been mapped.
Abstract: A new ectodermal dysplasia syndrome was reported by Bork et al. in 1987 (Hautarzt 38:342-347). The syndrome consisted of hypotrichosis with the typical SEM (scanning electron microscopy) changes of uncombable hair, retinal pigmentary dystrophy, juvenile cataract, oligodontia, brachydactyly with brachymetacarpia; it was inherited as an autosomal dominant trait. We describe a sporadic case and add further clinical findings to expand the spectrum of this rare syndrome.
Abstract: The authors report on a technique for the treatment of congenital lobar emphysema in a patient of 6.5 kg body weight. After left thoracotomy and vessel isolation, a section of the lobar bronchus and interlobar fissure was performed, because of incompleteness of 3/4 of its length. Metal clips were used with the stapler ENDO-GIA 30v Autosuture after tissue calibration. The authors underline the importance of the staplers, which have been widely used in adult surgery, because they reduce the risk of bacterial contamination and air leakage through the suture rims, especially in lung resective surgery.
Abstract: Intraabdominal calcifications are an unusual radiographic finding in the newborn and can easily be misinterpreted as meconium peritonitis. The authors refer to a patient with anorectal malformation (ARM), intraluminal calcifications and other anomalies. Careful differentiation of the type of intraabdominal calcifications can suggest the possibility of other initially unsuspected anomalies.
Abstract: Down's syndrome is the most frequent chromosomal anomaly in humans and sometimes is associated with anorectal anomalies. The anorectal malformations include many varieties of anatomical anomalies, which are often difficult to evaluate. The Authors believe preoperative CT or MRI of the pelvis, together with other clinical and radiological examination to be a valid mean in the preoperative prognostic evaluation. In this study they analysed the association of anorectal malformations and Down's syndrome and the absence of a genito-urinary or perineal fistula.
Abstract: In this study of 14 patients with anorectal anomalies CT and MRI were employed for preoperative assessment. The use of a pressure enhanced water soluble enema via the colostomy proved to be an extremely efficient method for showing a fistula. MRI studies were enhanced by the use of vaseline oil and in one case this technique was used prior to surgery to provide important information by injecting through a perineal fistula. CT and axial MRI proved to be more valuable than sagittal MRI which is only useful for the length of the atretic segment. The authors consider that a combined approach using pressure enhanced water soluble enema and MRI will provide the most valuable preoperative information to plan a successful operative approach and enable an accurate prognostic evaluation of continence in these difficult and complex patients.
Abstract: Four unrelated cases of congenital diaphragmatic hernia associated with ipsilateral upper limb reduction defects were reported by McCredie and Reid in 1978 (J Pediatr 92: 762-765). As contiguous segments of the cervical neural crest are involved in the development of diaphragm and arms, the authors suggested that an early injury to the cervical neural crest might be the common underlying pathogenesis. We describe here a further example of this malformation complex: a newborn with a left posterolateral diaphragmatic hernia associated with ipsilateral thumb hypoplasia.
Abstract: We describe two siblings, a male and a female pair, born of consanguineous parents, affected with a rare genetic form of congenital microcephaly. The clinical syndrome is characterized by early onset myoclonic seizures, spasticity, and profound psychomotor retardation without detectable brain malformations. To date, only two kindreds and one sporadic case with a similar clinical picture have been observed and reported (Tolmie et al. 1987, Bundey & Griffiths 1977). The severity of the neurological features and their perinatal onset differentiate the syndrome from the more common autosomal recessive microcephaly with spasticity/seizures.
Abstract: Posterior sagittal approach is very useful for the correction of anorectal malformations, but it can be used also for the treatment of pelvic or perineal masses. The authors present 3 patients affected one by a perineal hamartoma, one by a rectal duplication and one by a retrorectal cystic teratoma. All the patients were treated following the PSARP technique, using the Penã's bipolar electro-stimulator just in order to respect all the muscles of the anorectal sphincters. Using this procedure the authors were able to preserve the full anorectal continence in all the 3 patients.
Abstract: Isolated oesophageal leiomyomatosis in children is very rare. The association between leiomyomatosis of oesophagus and female genital tract and an Alport like hematuric nephritis has been recognized as a distinct entity by Garcia-Torres and Guarner. Since then few other cases of this syndrome have been observed. Congenital cataracts and neurosensory deafness have been added to the clinical spectrum. Autosomal dominant inheritance is suggested by the familial cases. We report a patient who presents, as a new finding, leiomyomatosis of the rectum.
Abstract: Anorectal malformations include a variety of anatomical anomalies which are often difficult to assess. Thirty-four patients (age range: 1 month-19 years) were studied over a 4-year period, 14 of them preoperatively and 20 postoperatively. In addition to inverted lateral plain films, a barred Iopamiro enema was performed in 13 of 14 cases by a Foley's catheter via colostomy. Endocolic pressure could thus be increased, which allowed the detection of rectal fistulas in 11 of 13 cases. Preoperative CT was performed in 9 cases, and MRI in 5. Both CT and axial MR scans provided accurate images of sphincteric muscles: they were well developed in 7 patients and poorly developed in 6; in 1 case the muscles were not identified. Sagittal MR scans only demonstrated the distance between blind pouch and perineum. Sagittal MRI also provided images of the spine (1 patient exhibited tethered cord). In the postoperative management, except for severe sacral anomalies, miscentered puborectal muscle and hypoplastic musculature were observed as the most frequent causes of fecal incontinence in patients treated with abdomino-perineal pull-through of the colon. To select the cases who needed reoperation, most frequently secondary PSARP, 17 patients were studied by CT and 7 by MRI; both techniques were employed in 4 cases. In 6 patients good development of sphincteric musculature and neo-anorectum correctly positioned within were observed. In 4 cases the neo-anorectum was correctly positioned, but sphincteric muscles were too hypoplastic to allow good continence; in 10 patients with incontinence, the neo-anorectum was seen outside sphincteric musculature: in 2 cases the latter was well developed (1 patient had had severe surgical damage to levator ani), while in 8 it appeared to be poorly developed. In our experience, postoperative CT allowed a correct evaluation to be made, whereas MRI failed to yield additional information.
Abstract: The study of anorectal malformations has considerably improved over the last years also thanks to the use of such diagnostic techniques as CT and MR imaging, which allow a better knowledge of perineal region anatomy and the demonstration of the development of sphincteric structures. The most important diagnostic phase for the identification of anorectal malformations consists in the detection of rectal fistulas. The authors report on their experience with barred water-soluble contrast enema in the study of anorectal anomalies. Over 2 years, 23 patients with anorectal malformations (10 males and 13 females) previously submitted to colostomy, were studied with this method. Fistulas were detected in 21 cases; in the extant 2 patients (both females affected with Down syndrome), no fistulas were detected, not even at surgery, which was posterior sagittal anorectoplasty according to Peña-De Vries. In our experience, the most frequent anomalies were recto-bulbo-urethral fistula in males and low recto-vaginal fistula in females. The authors suggest the use of this method as a routine diagnostic examination, because of its proven reliability.
Abstract: The authors describe the case of a family in which two siblings affected by cleft palate and cheiloschisis were diagnosed as suffering from van der Woude's syndrome (VWS). The diagnosis was largely determined by the finding of mucous cysts (lip-pits) on the lower lip of the two patients and their mother. Classification as VWS enabled genetic counseling as to the risk of recurrence to be modified from multifactorial to autosomal dominant. The authors also consider aspects of differential diagnosis among van der Woude syndrome, pterygo -popliteal syndrome and labio or palatoschisis syndrome with filiform fusion of the eyelids.
Abstract: In spite of the progress in the field of surgical treatment of anorectal malformations, faecal incontinence is, in variable degrees, still an unpleasant and frequent postoperative sequela. Postoperative CT demonstrate the location of the pulled-through intestine, including whether it had been correctly placed through the levator ani and in the spincteric muscular complex. In our nine patients we discovered a correlation between the CT findings and the clinical picture. The cases of incontinence whether associated with sacral anomalies or not were characterized either by marked hypoplasia of musculature or by the pull-through having missed the sphincteric musculature. CT scans could be of use in planning further surgery.
Abstract: The anatomical patterns of anorectal malformations have so far been studied according to the principles which inspire Peña's technique for the surgical treatment of anorectal anomalies. Thus, the diagnostic study of anorectal malformations has by the authors been considered a work of classification, but of identification. Among the diagnostic procedures in use in our Institute, preoperative CT of pelvis is performed to assess the presence and to define the development of muscular sphincteric structures towards prognostic evaluation of continence, the major long-term goal. Seven patients, aged 1-30 months, with anorectal anomalies were studied with preoperative CT of the pelvis. CT scans showed well-developed sphincteric muscles in 3 patients (2 with rectoureteral and 1 with rectovestibular fistulas), poorly developed muscular structures in 3 patients (with rectovaginal, cloacal and prostatic fistulas), absence of muscular structures in 1 case (with rectovesical fistula). CT findings were always confirmed at surgery, except for the case with rectovesical malformation where CT scans did not allow to identify the thin sphincteric musculature. The authors believe preoperative CT of the pelvis, together with other clinical and radiological examinations, to be a valid mean in the prognostic evaluation of continence.
Abstract: The radiological findings pathognomonic of Hirschsprung's disease have been known for quite a long time. However, in addition to those diseases characterized by rectum or rectum-sigmoid aganglionosis (as in the classic form of Hirschsprung's disease), in pediatric pathology of surgical interest severe affections exist characterized by aganglionosis extending from the rectum to the entire colon, and exceptionally as far as the small bowel (ultra-long Hirschsprung's disease). The authors report on the results they obtained in radiological studies of 6 cases of total colonic aganglionosis by means of the current radiological procedures, i.e. plain abdominal films and barium enema. As for total colonic aganglionosis, no diagnostic radiological parameters have been assessed yet. The authors compare their results with those taken from international literature: microcolon with reflux into mega-ileum (2 out of 6 cases) appears to be the most suggestive X-ray finding for total colonic aganglionosis. Finally, the role is discussed of radiological studies in the diagnostic approach to total colonic aganglionosis. The authors conclude that, even though radiological investigations are indispensable, they are often not conclusive. Therefore, an accurate evaluation of the proximal extension of aganglionosis can be made only at surgery.
Abstract: In spite of great progress in surgical treatment of anorectal malformations, fecal incontinence is still, in variable degrees, a frequent and unpleasant postsurgical sequela. The most frequent causes of incontinence are: i) the incorrect placement of the pulled-through colon in the levator ani and sphincteric muscular complex during abdominoperineal surgical procedures; ii) the poor development of sphincteric musculature; iii) the associated sacral anomalies. Postoperative CT helps to evaluate all the above-mentioned conditions, in view of possible new surgical procedure for improving continence (besides postoperative CT can help in choosing the more suitable surgical technique). Nine patients, aged 3 to 13 years, (2 with good continence and 7 with various degrees of incontinence), were studied with pelvic postoperative CT. In the cases (2) with good continence the CT picture was: good development of sphincteric musculature and neo-anorectum correctly placed into sphincteric musculature; in the cases (3) with low degree of continence: neoanorectum correctly placed, but hypoplastic puborectal muscle; in the cases (4) with complete incontinence, neoanorectum incorrectly placed and poor development of sphincteric musculature. A further posterior sagittal anorectoplasty (according Peña) is only suitable in the incontinence cases with: i) neoanorectum seriously misplaced; ii) good development of sphincteric musculature; iii) absence of sacral anomalies. Postoperative CT is a valid mean for demonstrating all the above-mentioned conditions and for choosing the best surgical technique in each case.
Abstract: The authors describe 6 cases of Apple Peel Small Bowel observed in the last ten year experience in Institute G. Gaslini of Genoa, Italy. They make a precision on early diagnosis and on surgical treatment, which is original, and also on post-operatory medical treatment. The importance of making an optimal nutritional support with total and partial parenteral nutrition for long time is of great significance to have a better outcome and psycho-physical development in such patients.
Abstract: Intraoperative biopsies are required to confirm diagnosis of Hirschsprung's disease and to determine exact extent of aganglionism. Authors report a new method for enzymo-histochemical intraoperative evaluation of aganglionic segment. Activity of non specific esterase (following Davis and Orstein technique, 1959) has been used to demonstrate presence or absence of intramural ganglion cells in sero-muscular intestinal biopsies, which had been taken at various levels in 34 patients with preoperative diagnosis of Hirschsprung's disease. Authors consider histochemical technique as the most reliable, quick, simple and low-cost method for intraoperative evaluation of the length of aganglionic segment and, of course, to confirm diagnosis. Alpha-naphthyl-esterase is also of great help in the study of so-called pseudo-Hirschsprung.
Abstract: We have histochemically evaluated the LAP, AP and ANE activities of the human appendix in 100 surgical specimens. The mucosa has been particularly investigated for its different aspects during inflammatory conditions. Two main facts have been ascertained: the subepithelial location of macrophages, and the AP and ANE activities of two groups of cells in the germinal centers. Subepithelial macrophages show conspicuous AP activity that correlates with the degree of inflammatory response and of exposure to luminal antigens. In the germinal centers, AP and ANE activities disclose two further groups of positive cells, probably the same cells reacting to both technics. One group is rooted to the core of the germinal center; the other to the intermediate area between the germinal center and the follicular mantle.
