Multiple biomarkers improve the prediction of multiple sclerosis in clinically isolated syndromes.

OBJECTIVES: Since its introduction, MRI had a major impact on the early and more precise diagnosis of multiple sclerosis (MS), and the 2010 diagnostic criteria even allow a diagnosis to be made just after a single attack if stringent MRI criteria are met. Several other clinical and paraclinical markers have been reported to be associated with an increased risk of MS independently of MRI in patients with clinically isolated syndromes (CIS), but the incremental usefulness of adding them to the current criteria has not been evaluated. In this study, we determined whether multiple biomarkers improved the prediction of MS in patients with CIS in a real-world clinical practice. MATERIALS AND METHODS: This was a retrospective study involving patients with CIS admitted to our department between 2000 and 2013. We evaluated baseline clinical, MRI, neurophysiological, and cerebrospinal fluid (CSF) data. RESULTS: During follow-up (median, 7.2 years), 127 of 243 participants (mean age, 31.6 years) developed MS. Cox proportional-hazards models adjusted for established MRI criteria, age at onset, number of T1 lesions, and presence of CSF oligoclonal bands significantly predicted the risk of developing MS at 2 and 5 years. The use of multiple biomarkers led to 29% net reclassification improvement at 2 years (P<.001) and 30% at 5 years (P<.001). CONCLUSIONS: The simultaneous addition of several biomarkers significantly improved the risk stratification for MS in patients with CIS beyond that of a model based only on established MRI criteria.

Continence and quality of life with the modified Heitz-Boyer-Hovelacque rectal bladder for children with urinary incontinence following bladder exstrophy.

BACKGROUND: Bladder exstrophy and epispadias are severe congenital anomalies associated with an open bladder and urinary sphincter. Despite modern reconstruction, there is a significant incidence of residual or recurrent urinary incontinence that impacts on quality of life (QoL) and self-esteem, which in turn limits social interaction (Figure). The present study involved 14 patients, mainly from a Middle Eastern country, and reported the early findings with a modification of the Heitz-Boyer-Hovelacque rectal bladder technique for both urinary and faecal control. STUDY DESIGN: Fourteen children, with a median age of 8.1 years, with poor quality of life and low self-esteem because of urinary incontinence and small polypoidal open bladders of 5-15 ml volume, mostly after bladder exstrophy surgery, were managed with a modification of the Heitz-Boyer-Hovelacque rectal bladder technique keeping an intact anal sphincter. The retrorectal pulled-through colon was anastomosed to the posterior wall of the rectum just above the external sphincter complex, thereby avoiding any possible injury to the anal sphincter. All patients had a normal colon and a competent anal sphincter without lumbosacral spinal or nerve anomalies. RESULTS: Ten children had a 5- to 10-year follow-up, one child had a 15-year follow-up, and three others, that were also continent, were excluded because of a <5-year follow-up. There were no postoperative complications, and all were dry and odour-free by day within 2-4 weeks of surgery. Two children still had minor urinary loss at night. There were no UTIs and renal function remained unimpaired. Eleven years after surgery, one child underwent excision of a pedunculated benign inflammatory polyp from the tip of the left ureter because of recurrent torsion and bleeding, there was no recurrence at the 2-year follow-up. None of the rectal or ureteric biopsies from any of the children showed metaplasia or neoplasia; however, in view of the potential long-term risks, all children were placed on a lifelong 'proctoscopy and biopsy' protocol. DISCUSSION: The ability to be dry and odour-free, and to wear normal clothing had a striking impact on QoL and psychological well-being of the children and their families. This was reflected in their positive overall approach, voluntary school attendance, and enthusiastic participation in communal events. All agreed that their improved genital appearance markedly contributed to their better body image and increased self-esteem. CONCLUSION: These significant benefits, at a crucial time in the child's life, outweigh the potential risk of long-term neoplasia. Therefore, the Heitz-Boyer-Hovelacque rectal bladder technique is recommended with long-term proctoscopic follow-up.

Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add-on treatment of motor symptoms in Parkinson's disease: an open label, pilot study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a potential treatment for Parkinson's disease (PD). H-coils, inducing deeper and wider magnetic fields compared to traditional coils, may be potentially useful in PD, characterized by widespread, bilateral involvement of cortico-subcortical circuits. OBJECTIVE: To evaluate the safety of repetitive deep TMS (rDTMS) with H-coil as add-on treatment of motor symptoms in PD. METHODS: Twenty-seven PD patients (aged 60.1 ± 6.8 y; PD-duration: 6.3 ± 2.8 y; motor-UPDRS: 39.6 ± 10.1) underwent 12 rDTMS sessions over 4 weeks at excitatory (10 Hz) frequency over primary motor (M1) and bilateral prefrontal (PF) regions. Motor UPDRS off therapy was assessed before and after the last rDTMS session, together with safety records at each treatment session. RESULTS: No drop-outs or adverse events were recorded. Motor UPDRS significantly improved after rDTMS (10.8 points average reduction; P < 0.0001). CONCLUSIONS: High-frequency rDTMS might be a safe treatment for PD motor symptoms. Further placebo-controlled, randomized studies are warranted.

Ileostomy in extremely low birth weight and premature neonates.

AIM: The establishment of an ileostomy is a surgical option in the treatment of neonatal intestinal diseases, such as necrotizing enterocolitis (NEC) and meconial disease, in premature or extremely-low-birth-weight (ELBW) infants. METHODS: A prospective study was performed between July 2000-April 2011, with in exam all cases of acute abdomen in newborn premature babies. We perfomed a temporary ileostomy with a skin bridge and resection of the necrotic intestine. The temporary ileostomy was followed by anastomosis and the effect of possible confounding factors were assessed on the intestinal canalization. Data analysis and multiple monovariate were conducted. RESULTS: Thirty-three neonates, 14 males and 19 females, operated for intestinal perforation were identified. They were ELBW or premature neonates. There were 24 neonates with NEC, 4 with meconium peritonitis and 5 with complicated meconium ileus. In 4 cases of meconium ileus we found ileale atresia. Eight patients were excluded from the study because 3 died; 2 had cystic fibrosis and 3 with hydrocephalus. Thirteen patients developed complications: 7 related to ileostomy, 2 cholestasis and 4 recurrent NEC. Patients with meconium ileus gain rcovery of bowel function 4 days or more the others (OR=8.0; P=0.0455). CONCLUSION: In our experience, the establishment of ileostomy for the treatment of acute abdomen in child newborn premature or low birth weight allows optimal management of the child, excluding bowel sick and faster healing with a low rate of morbidity and mortality.

Intrauterine volvulus with malrotation: prenatal diagnosis.

Volvulus is a very rare condition which consists of the rotation of the small intestine and the proximal colon around the superior mesenteric artery, leading to complete intestinal obstruction and ischemic vascular damage. The frequency of this condition is 1 in 6000 live births. We report a case of midgut vovulus with malrotation with a prenatal diagnosis at the end of the week 33. We describe the importance of prenatal echotomographic diagnosis which offers the possibility of performing differential diagnosis. Additionally, it is important to remember that the prognoses of these patients depend on the length of remaining intestine, the location of the intestinal obstruction, the presence of meconium peritonitis, the possibility of associated malformations, but above all, on birth weight and level of prematurity.

Idiopathic spontaneous intestinal perforation: a distinct pathological entity in the preterm infant.

AIM: Necrotizing enterocolitis (NEC) is the most common cause of intestinal perforation in newborn children. A novel condition of idiopathic spontaneous intestinal perforation (SIPI) was recently described, which does not show clinical and diagnostic features of NEC. The aim of the present study was to define clinical peculiarities and potential risk factors in newborns by comparing SIPI and NEC patients. METHODS: In the last six years, 85 preterm infants have necessitated surgical counseling for acute abdominal conditions. Among them, 13 underwent emergency surgery, 6 for SIPI and 7 for NEC respectively. Patients were then subdivided into three groups: group 0: 72 infants who did not need surgery; group I: 6 patients with SIPI; group II: 7 patients with NEC. Some variables were retrospectively analyzed and were compared by means of chi(2) test with a significant value of P<0.05. RESULTS: No association emerged between patient's sex gender (P=0.691), membrane ruptures (P=0.400) and maternal infection (P=0.415). A correlation was observed between pneumoperitoneum and SIPI/NEC (P=0.000). The study on group I and II showed a lower gestational age (27.3 as compared to 30.28 weeks) and a higher number of membrane ruptures (4/6 as compared to 3/7) and of maternal infections (4/6 as compared to 3/7). CONCLUSIONS: This study showed that a determining factor for the etiopathogenesis of SIPI may be neonatal stress consequent to preterm birth. Infants under 28 weeks of gestational age, with low birth weight, show a particular predisposition to SIPI, with a risk accounting to 96% of the present case series.

[Neonatal neuroblastoma and prenatal diagnosis]. / Neuroblastoma neonatale e diagnosi pre-natale.

The improvement of the imaging has considerably increased the number of cases of neuoroblastoma, diagnosed in preborn age. The authors present a case of neonatal neuroblastoma diagnosed in prenatal age and managed with a multidisciplinary approach. The authors report the case of R.T., born from a scheduled Caesarean delivery. The echographic morphological prenatal diagnosis showed an abdominal mass of 3x2 cm located on the upper side of the kidney, which was not apparently involved. Postnatal ultrasound evaluations confirmed that diagnosis. The diagnostic programme included nuclear magnetic resonance and a renogramm with metaiodobenzylguanidine. These exams confirmed the presence of a mass, probably due to a neuroblastoma. Due to the increasing of the mass, the patient underwent surgical excision of the neoplastic mass. The histological examination confirmed the diagnosis of neuroblastoma Stage I without medullary involvement. During the operation, a medullary biopsy was performed. The FISH exam did not show the amplification of N-myc or a delection of p36 chromosome. For patients younger than 18 months there is no therapeutic gold standard for the treatment of suprarenal masses of neoplastic origin, and the approach is still controversial. The complete excision of the mass should be taken in consideration in presence of an increasing neoformation, and should not include any chemotherapeutical or radiation therapy for stage I, II, IVs (INSS) or L1, MS (INGRSS) neoformations. In conclusion, the effectiveness of a multidisciplinary approach of neonatal neuroblastoma is higher in the early diagnosis and in an accurate staging of the disease, which is fundamental for the favourable prognosis.

Second-line chemotherapy in advanced pancreatic carcinoma: a multicenter survey of the Gruppo Oncologico Italia Meridionale on the activity and safety of the FOLFOX4 regimen in clinical practice.

BACKGROUND: In daily clinical practice second-line chemotherapy (SLCT) is frequently given to patients with advanced pancreatic cancer failing gemcitabine-based first-line chemotherapy without solid scientific support. PATIENTS AND METHODS: A retrospective survey was carried out including 42 patients. Patients received standard FOLFOX4 regimen biweekly until progression or unacceptable toxicity. RESULTS: Six partial responses (14%) and 16 stabilizations (38%) were recorded for a tumor growth control rate of 57%. The median time to progression (TtP) was 4 months (range 1-7 months), and median overall survival (OS) was 6.7 months (range 2-9 months). A stabilization of performance status (PS) and a subjective improvement of cancer-related symptoms were recorded in 27 patients. CONCLUSIONS: Data presented in this paper support the use of FOLFOX4 regimen in the second-line treatment of adenocarcinoma of the pancreas patients. The use of SLCT, however, should be carefully proposed to patients with good PS or those who had a good response to first-line therapy.

Testicular hypotrophy in varicocele: pre and postoperative echographic follow-up in the pediatric age.

AIM: Varicocele is characterised by an anomalous tortuosity and dilation of the veins of the pampiniform plexus. The etiopathogenetic mechanisms are still unclear, but a correlation seems to exist between varicocele and testicular development, with possible repercussions on the testicle's functionality. The aim of this study is to evaluate gonadic trophism through echographic monitoring in the pre and postoperative phases in patients affected by idiopathic varicocele with testicular hypotrophy in order to evaluate the treatment's benefits. METHODS: Sixty-six patients (mean age 12,5; range 10-17) consecutively operated for left idiopathic varicocele were considered. Of these, 27 had ipsilateral testicular hypotrophy and thus they were included in the study. Fifteen were operated upon in videolaparoscopy (VLS), and 12 by the classic open inguinal access. The mean follow-up was 18 months (6-24 months). The data were analyzed by nonparametric Mann-Whitney U test. RESULTS: An increase in the testicular volume was observed clinically and by ultrasound in 13 of the 15 patients treated by VLS and in 9 of the 12 patients operated by traditional means. The nonparametric Mann-Whitney U test showed a significativity between pre and post-operative values. CONCLUSION: The testicular trophic healing observed in 81.5% of the operated patients leads to the belief that an early correction can allow a rapid volumetric increase and an improved function of the gonad.

[Treatment of varicocele in pediatric age with retroperitoneoscopic ''one trochar'' technique. Long term follow-up]. / Trattamento del varicocele in etá pediatrica in retroperitoneoscopia, con tecnica ''one trocar'' follow-up a lungo termine.

AIM: The incidence of varicocele varies from 6% to 16.2% in male children and adolescents. Various techniques were proposed to treat it. In the last years there was an increasing interest in the use of laparoscopy in pediatric urology. The authors reports their experience in the treatment of varicocele by retroperitoneoscopy with one trocar technique and the long-term follow-up in pediatric patients. METHODS: Fourty patients were treated for idiopathic Horner's degree III or less, but symptomatic, and type 1 according to Coolsaet varicocele. All patients underwent a clinical examination and echo-color Doppler before treatment and during the follow-up. RESULTS: The following parameters were evaluated: duration of the operation, intra and postoperative complications, duration of hospitalization and of antalgic therapy. Follow-up was at 6, 12, 24 and 36 months (mean 23.4 months). Testicles diameters, persistence/recurrence of varicocele and hydroceles were estimated. CONCLUSIONS: The retroperitoneoscopic approach in the treatment of varicocele is an effective technique because it implies a minor surgical trauma, a rapid postoperative recovery and a good cosmetic result.

Voluminous perinatal pelvic mass: a case of congenital hydrometrocolpos.

Imperforate hymen is the most frequent congenital malformation of the female genital tract; it usually does not show symptoms until puberty. Only rarely, imperforate hymen manifests itself as an abdominal mass detectable in the prenatal period. We describe a rare case of voluminous hydrometrocolpos, antenatally diagnosed and successfully treated immediately after birth.

[Treatment of varicocele in the pediatric age: videolaparoscopic versus "traditional" open techniques]. / Trattamento del varicocele in età pediatrica: tecnica VLS vs open.

AIM: Varicocele is determined by an ectasia of the veins of the pampinous plexus, and its incidence ranges from 2% to 16% in the different ages. Etiology and pathogenic mechanism are not clear; on the other hand it is absolutely certain that an early onset of varicocele in the pre-puberal age can heavily condition testicular development and function, with a condition of hypo-infertility which will be irreversible in the adult age. Up to date, there are not clear data allowing to state a "gold standard" therapy, although there is a general goodwill in affirming the usefulness of an early operation to prevent a gonadic damage. The aim of our study was to carry out an accurate analysis of post-operative clinical and instrumental data and to point out advantages and disadvantages of the traditional surgical technique versus the more recent videolaparoscopic technique (VLS). METHODS: Twenty-eight patients were consecutively treated for hydiopathic, III Horner degree, I Coolsaet degree left varicocele. In the first 15 patients an "open" operation was performed, while in the other 13 VLS technique according to Palomo was used. RESULTS: Follow-up, based on 9 different parameters, such as duration of hospitalisation and postoperative recovery was continued for a mean period of 18,67 months. CONCLUSIONS: An analysis of the results showed that both techniques are effective, although VLS can offer advantages as far as reduction of hospitalisation, reduction of duration of operation and postoperative recovery are concerned, as well as an increasing of compliance due to a better cosmetic result.

Laparoscopic diagnostic exploration of the vaginal processus in the pediatric age. Preliminary experiences.

BACKGROUND: Laparoscopic surgical procedures, employed even in the paediatric age, bearing both diagnostic and therapeutic value, are currently used in the evaluation of peritoneal-vaginal duct patency during surgery for controlateral inguinal hernia or other diseases requiring opening of abdominal wall. METHODS: From January 1996 to December 2000, at the Department of Pediatric Surgery of the University of Siena a prospective study protocol has been performed to evaluate the effectiveness of laparoscopy versus traditional surgery in showing patency of peritoneal-vaginal duct. RESULTS: From our study we have been able to see how this laparoscopic procedure is well tolerated by children and parents, and is lacking in clinical complications. Patency of peritoneal-vaginal duct has been pointed out in 21.73% of cases. This result is in line with the international literature; in fact, the majority of authors have found a negative controlateral exploration in 50-80% of patients examined, thus confirming the uselessness of routine surgical controlateral inguinal exploration in hernia cases. CONCLUSIONS: The use of diagnostic laparoscopy in the study of peritoneal duct patency is a rapid and relatively easy technique, practically without intra- and peri operative risks. It allows an easy solution of the diagnostic doubt, without the need to necessarily perform a traditional explorative surgical procedure.

Absence of the inferior labial and lingual frenula in Ehlers-Danlos syndrome.

The diagnosis of Ehlers-Danlos syndrome is based on distinctive phenotypical characteristics such as hyperelastic skin and hypermobile joints. To date, no congenital physical markers exist for identifying patients with Ehlers-Danlos syndrome. Absence of the inferior labial (100% sensitivity; 99.4% specificity) and lingual frenulum (71.4% sensitivity; 100% specificity) was found to be associated with classical and hypermobility types of Ehlers-Danlos syndrome.

Infantile hypertrophic pyloric stenosis and asymptomatic joint hypermobility.

A significant association with asymptomatic joint hypermobility was observed in 37 children with a history of infantile hypertrophic pyloric stenosis (P =.0016) and their parents (mothers, P <.0001; fathers, P <.05). The subjects with articular hypermobility showed an increased frequency of absent mandibular frenulum, thereby suggesting the presence of a previously unrecognized, systemic abnormality of the extracellular matrix.

[Idiopathic constipation in children: 10-year experience]. / La stipsi idiopatica in età pediatrica: 10 anni di esperienza.

Constipation is a frequent clinical disorder in pediatric age and it is often difficult to resolve without a suitable diagnostic and therapeutic approach. Parents and pediatrician often underestimate this pathology, reaching the specialist only when it has already shown its complications. In the Department of Pediatric Surgery of Siena, in the last 10 years, we have activated a study centre on constipation in the pediatric age and we have developed a diagnostic and therapeutic protocol to give indications on the type of constipation and the consequent therapy. The Authors report their experience on 174 children with chronic constipation. The patients underwent a scintigraphic colonic transit time evaluation by radionuclides, an enema and an anorectal manometry. Such examinations were able to divide patients into two groups: with colonic and rectal constipation. The management consisted in common dietetic, behavioural and pharmacological treatment at first and then of specific treatment (biofeedback, prokinetic, emicolectomy), according to the type. The follow up showed recovery or improvement in 83.53% cases, unchanged clinical condition in 8.57%, aggravation in 1.9%. The Authors conclude emphasising the importance of diagnostic techniques that allow to frame correctly the pediatric patient affected by constipation. Particularly the anorectal manometry can be considered a first level examination, able to identify rectal constipation; together with scintigraphic colonic transit time that individualizes colonic constipation. The right diagnosis will be able to give a suitable therapeutic treatment.

Hypoplastic or absent mandibular frenulum: a new predictive sign of infantile hypertrophic pyloric stenosis.

Among 25 patients with hypertrophic pyloric stenosis, a hypoplastic or absent mandibular frenulum was noted in 92%, compared with 1.6% of 319 control infants (P <.001). This previously unrecognized sign may prove helpful in identifying newborns at risk of developing the disorder.

Congenital cystic adenomatoid malformation of the lung associated with esophageal atresia and tracheoesophageal fistula.

Bronchopulmonary malformations associated with esophageal atresia (EA) and tracheoesophageal fistula (TEF) are extremely rare. The authors describe a case of type II congenital cystic adenomatoid malformation (CCAM) of the right lower lobe associated with EA and TEF (Vogt-Gross type C) in a full-term female infant. The CCAM presented as an incidental radiologic finding, and a contralateral tension pneumothorax developed shortly after surgical repair of the EA. Early recognition of this rare association is essential for correct operative management.

[Varicocelectomy by an inguinal approach. Our experience]. / Varicocelectomia per via inguinale. Nostra esperienza.

Varicocele is a dilatation of the spermatic plexus due to a pathologic venous reflux in the testes. It affects about 15-18% of adolescents. The modern diagnostic tools allow an early identification and a thorough staging. Surgical treatment in this phase seems to be useful for the preservation of gonad integrity. Recently, the interest in varicocele in pediatric surgery has increased because of the close relationship of this disease to male infertility. We performed a diagnostic-therapeutic protocol with a follow-up to evaluate the trophism and functional state of testes and to identify early recurrence of venous reflux. In our Institute, the surgical treatment usually performed is resection of spermatic plexus through an inguinal approach. This technique is simple, yields good outcome and has no morbidity.