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.

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.

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.

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.

Intrauterine volvulus without malrotation in a very low-birth-weight preterm infant.

Midgut volvulus without abnormalities of intestinal rotation/fixation is an extremely rare cause of acute intestinal obstruction in the neonatal period with a high morbidity and mortality. The authors describe an intrauterine volvulus without malrotation in a 970g preterm girl born at 27 weeks' gestation. The discrepancy between minimally evocatory clinical manifestations and severity of intestinal pathology is underscored. Resection of the necrotic bowel and primary end-to-end anastomosis within 30 hours of birth was followed by a favorable outcome. A literature review indicates a significant relation of intrauterine midgut volvulus without malrotation to preterm birth with low-birth-weight, immediate postnatal presentation and favorable prognosis.

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.

[Spleen autotransplant. Natural history and description of a case]. / L'autotrapianto di milza. Storia naturale e descrizione di un caso.

After considering the natural history of spleen auto-transplant, a clinical case followed up for seven months with instrumental (echography, scintigraphy) and humoral (Jolly bodies, Heinz bodies, reticulocytes, platelets, complement, immune globulin) examinations has been considered so as to verify "take" and function. One months after reimplantation the patient was again operated on for the onset of an intestinal occlusion due to adherences. On that occasion it was possible to control that the implant had taken. It is concluded that personally used parameters proved to be well correlated and that scintigraphy and echography are two complementary, effective techniques for monitoring auto-transplants.

[High dose chemotherapy in metastatic carcinoma of the breast]. / Chemioterapia ad alte dosi del carcinoma della mammella metastatico.

PURPOSE: To verify tolerance and clinical efficacy of high-dose chemotherapy (HDCT) in metastatic breast cancer (MBC). PATIENTS AND METHODS: We submitted to HDCT with autologous peripheral blood cells transplant 66 patients, with MBC responding to induction chemotherapy. The condizioning regimen was ICE: iphosphamide 3.3 g/m2 dd. -8/-6, carboplatin 450 mg/m2 plus etoposide 400 mg/m2 dd. -5/-3 (21 patients = 78%); CTM: cyclophosphamide 100 mg/kg dd. -4/-3, tyothepa 500 mg:m2 d.-5, mytoxantrone 40 mg/m2 d. -6 (6 patients, 22%). RESULTS: Median number of aphereses was 2 (range 1-5), median amount of CD34+ cells/kg bw of 10 x 10E6 (range 3.5-38.2). Median recovery time was 10th day for PMN (range 8-37) while for platelets it was 9th day (range 8-37): total hospital stay was of 24 days (range 22-48). After induction therapy we had PR in 13/27 metastatic patients (48%) and CR in 14/27 (52%). After conditioning treatment we had PR in 12/27 (44%) and CR in 15/27 (56%). Median time to progression was 19 months (range 7-38) and median survival 52 months (range 7-59+), with 30% surviving beyond 4 years. CONCLUSIONS: Feasibility of HDCT in advanced breast cancer seems verified. The promising results need to be confirmed.

[Prognostic aspects of esophageal ph-metry in infants with reflux]. / Aspetti prognostici nella pHmetria esofagea del lattante reflussore.

Gastroesophageal reflux (g.e.r.) is a very common event in children particularly in infants. Twenty-four-hour continuous esophageal pH monitoring has become the preferred test to quantify acid gastroesophageal reflux. It has a large sensitivity and specificity, but it does not allow a good prediction of esophagitis. The Authors show a computerized method to determine the area under the curve (a.u.c.) and the percentage of time at different pH levels. These parameters have shown the same sensitivity and specificity as DeMeester-Boix-Ochoa score. They directly relate the time of exposure and pH level in every reflux under pH 4 and so they suggest a better prognostic index. To improve this approach to g.e.r. we will need other studies with this method.

[Hypertrophic stenosis of the pyloric canal: genetic and familial incidence]. / Stenosi ipertrofica del canale pilorico: incidenza genetica e familiare.

The Authors hereby review the literature concerning hypertrophic pyloric stenosis, with particular reference to the genetic and familial influence. They present their cases of 49 children; out of these 3 pairs of biovular twins out of which only one of the twin babies was affected and 2 similar twins both of which were affected. In conclusion they are confirming the importance of a genetic component, influenced by environmental factors, on the origin of hypertrophic pyloric stenosis.

[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.

[Epididymitis in children: cause of acute scrotum]. / Epididimite in età pediatrica: una causa di scroto acuto.

The acute epididymitis in children is an uncommon disease which occurs mainly in adolescents. The pediatric surgeon must remember this illness whenever he observes a child with acute scrotum. The aim of this study is to review our experience at the Pediatric Surgery Department in Siena with 17 children (mean age: 7.53 years) underwent to surgery for acute scrotum and affected by primitive acute epididymitis without any other local or systemic associated disease. Our study shows that in children the acute epididymitis is more common than testicular torsion. It is often quite difficult to find the origin of epididymitis in children with no genito-urinary anomalies; so the acute scrotum and in particular the epididymitis require a standardized diagnostic and therapeutic approach based on an accurate physical exam, quickly feasible diagnostic procedures and a prompt surgical exploration of the scrotum.

[Acute-phase proteins in appendicitis in childhood: new findings]. / Le proteine di fase acuta nell'appendicite in età pediatrica: nuove acquisizioni.

The diagnosis of acute appendicitis in children can be sometimes difficult. The monitoring of acute phase protein response has been suggested as an accurate diagnostic procedure in these patients. This response is an aspecific event caused by phlogosis, infections and traumatisms; it is accomplished by the hepatic release of "endogenous leukocytic mediators" (L.E.M.) among which can be remembered IL-6 and IL-7. The acute phase proteins can be distinguished into positive and negative factors. Many authors used the acute phase protein response in order to stratify the severity of disease, to evaluate the efficacy of therapy and to find out any complication. They actually think that this response is useful to draw up a prognostic index in each patient. This second part of a study started in 1994 is based on the evaluation of the preoperative acute phase proteins values in pediatric patients affected by acute appendicitis underwent to surgery. The results of the statistic analysis show the utility of the evaluation of these parameters in the preoperative period; in particular G.B. count and P.C.R. rates very early with significant statistics, while the other values change later and are more difficult to interpret.

[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.

[Use of radionuclides in the evaluation of intestinal transit time in children with idiopathic constipation]. / Impiego dei radionuclidi nella valutazione dei tempi di transito intestinale in bambini affetti da stipsi idiopatica.

Colonic transit times, in patients with chronic idiopathic constipation, in the past were estimated using radiopaque markers. Currently they are evaluated with colonic scintigraphy, which employs 111In DTPA orally, added to the usual children's breakfast in a 0.05 mCi dose. Anterior views of the abdomen are obtained at 6th, 24th, 30th, 48th, 54th, 72nd hour using a gamma camera on a 128 x 128 matrix and stored on hard disk. These images are processed in successive times, and the colon is divided in three main segments: right-, left- and recto-sigmoid-colon. Total and segmental percentage retentions are evaluated in each interval time. 58 children (35 males and 23 females), aged 1-12 years (mean 8.13), referred for chronic idiopathic constipation at Pediatric Surgery Department of Siena, were studied between January 1990 and September 1996. This group was compared with a control group formed by 15 patients (9 males and 6 females) aged 3-14 years (mean 8.53). Cutoff values, obtained in this control group, allowed us to distinguish, among the 58 children with idiopathic constipation, 6 symptomatic patients with normal colonic transit times and 52 symptomatic patients with pathologic ones. In this last group the evaluation of segmentary colonic transit times allowed us to identify 13 patients (25%) with increased right colonic transit time, 19 (36.5%) with increased left colonic transit time and 20 (38.5%) with increased recto-sigmoidal colonic transit time. Statistical survey allowed to distinguish significantly pathological subjects from control group ones.

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.

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.

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.