Anna Maria Fagnani

Features and outcome of neuroblastoma detected before birth

BACKGROUND/PURPOSE The growing use of routine ultrasonography during pregnancy is leading to an increasing number of prenatally diagnosed neuroblastomas. Optimal strategy has not yet been defined for these patients, because knowledge on this particular neuroblastoma (NB) population is still limited. However, definite guidelines are needed to avoid inadequate treatment. The authors analyzed the cases of antenatally detected NB (ADNB) reported in the Italian Neuroblastoma Registry during the past 6 years to elucidate the features of this subset of NB. METHODS The Italian Neuroblastoma Registry was reviewed for the period January 1993 to December 1998 to collect clinical, radiographic, surgical, and histopathological data on ADNB cases. NB stage was evaluated according to INSS criteria. All patients had undergone imaging (computed tomography or magnetic resonance imaging) of the primary tumor and bone marrow biopsy before surgical resection. RESULTS Seventeen patients were identified. Primary tumour site was adrenal glands in 16 cases and retroperitoneal ganglia in 1. Stage distribution was stage I, 13 cases; stage II-A, 1 case; stage II-B, 1 case; stage IV-S, 2 cases. All cases underwent primary tumour resection. Mean age at surgery was 4 weeks. Resection of primary tumor was radical in 16 cases, partial in 1. All tumors were characterised by favourable histology according to Shimada classification. N-myc gene amplification was studied in 14 patients. N-myc amplification was detected only in a newborn with stage II-A NB, who died of massive bleeding 2 days after tumor resection. DNA index and 1p deletion were studied in 11 and 8 patients, respectively. Both diploidy and deletion of 1p were observed in a newborn who subsequently died of disease progression despite surgery, chemotherapy, and radiation therapy. Fourteen of 17 patients currently are alive and free of disease, and one with IV-S NB and short follow-up is alive with disease. CONCLUSIONS Our data give evidence that in most cases infants with ADNB represent a subset of patients with excellent outcome. Aggressive treatment may not always be necessary. Infants with ADNB with unfavorable features should undergo early surgical excision, whereas patients with favourable features could be observed awaiting spontaneous regression of the mass, reserving delayed surgery for tumors that increase in size or do not regress.

Resection of primary tumor at diagnosis in stage IV-S neuroblastoma: does it affect the clinical course?

PURPOSE To determine whether resection of primary tumor has a favorable influence on outcome of infants (age 0 to 11 months) with stage IV-S neuroblastoma. PATIENTS AND METHODS Between March 1976 and December 1993, 97 infants with previously untreated neuroblastoma diagnosed in 21 Italian institutions were classified as having stage IV-S disease. Seventy percent were younger than 4 months. Adrenal was the primary tumor site in 64 of 85 patients with a recognizable primary tumor. Liver was the organ most often infiltrated by the tumor (82 patients), followed by bone marrow and skin. RESULTS The overall survival (OS) rate at 5 years in 80% and event-free survival (EFS) rate 68%. In 24 infants, the effect of resection of primary tumor could not be evaluated because of rapidly fatal disease progression (n = 8), absence of a primary tumor (n = 12), or partial resection (n = 4). Of 73 assessable patients, 26 underwent primary tumor resection at diagnosis: one died of surgical complications, one relapsed locally and died, and two others relapsed (one of these two locally) and survived, for a 5-year OS rate of 92% and EFS rate of 84%. Of the remaining 47 patients who did not undergo primary tumor resection at diagnosis 11 suffered unfavorable events, of whom five died, for an OS rate of 89% and EFS rate of 75% (no significant difference from previous group). Disease recurred at the primary tumor site in only one five who died, and in only one of six survivors of progression or relapse; in these patients, the primary tumor, located in the mediastinum, was successfully resected. CONCLUSION Infants who underwent resection of the primary tumor at diagnosis had no better outcome than those in whom the decision was made not to operate.

Neuroblastoma in the newborn. A study of the Italian Neuroblastoma Registry

AIM Presenting features, treatment and outcome of 134 newborns with neuroblastoma diagnosed over a 27-year period are described. METHODS Analyses were performed on the entire cohort and on patients distributed over three periods of diagnosis. RESULTS Twenty-seven tumours (20.1%) were detected prenatally. Localised disease prevailed (65.7%) with an increase of stage 1 patients over time from 18.8% to 46.5%. Disseminated disease accounted for 34.3% of tumours with only one stage 4 and 45 stage 4S. Five-year overall survival (OS) of the entire cohort was 88.3%. Five/88 patients with localised disease died, including three who died of complications (OS, 95.3%). The only stage 4 patient survived. Eleven/45 stage 4S patients died, including 7/18 symptomatic and 4/27 asymptomatic (OS, 74.1%). CONCLUSION The outcome of neuroblastoma in newborns is excellent. In localised tumours, surgery-related deaths outnumbered deaths due to disease. Symptomatic stage 4S patients were at greater risk of dying.

Appendiceal Neuroendocrine Tumours in Childhood: Italian TREP Project

Background: Neuroendocrine tumours (NETs) of the appendix are slow-growing tumours and, although rare, they are the most common gastrointestinal epithelial tumours in childhood and adolescence. The treatment and the follow-up screenings have not been standardised. In addition to this, although tumour size is considered the main prognostic variable to define the aggressiveness of approach, a precise cutoff needs to be established. Methods: A total of 113 patients younger than 18 years with a diagnosis of appendiceal NETs were registered as of January 1, 2000, until May 30, 2013, within the Rare Tumors in Pediatric Age (TREP) project, an Italian multi-institutional network dedicated to rare tumours in children and adolescents. The recommendations of the Rare Tumors in Pediatric Age study included imaging and laboratory investigations. The treatment after appendectomy was decided on the basis of histology, tumour size, and imaging; primary reexcision (PRE) was not recommended in completely excised tumours, regardless of tumour size and invasiveness. Results: A total of 113 of 113 patients had a diagnosis of well-differentiated NETs; in 108 of 113 the tumour was smaller than 2 cm and in 5, larger than 2 cm. Excision margins were free in 111 of 113 patients. In 3 of 113 a PRE was performed, and in 1 residual tumour was detected. All 113 of 113 patients are alive in complete remission (median follow-up of 41 months). Conclusions: Reported data and our experience showed that no relapse or death occurred in children and adolescents affected by appendiceal NETs. Appendectomy alone should be considered curative for most patients, and a more aggressive surgical approach is warranted in the cases with incompletely excised tumours.

Management and follow-up of urothelial neoplasms of the bladder in children: a report from the TREP project.

Urothelial neoplasms of the bladder (UNB) are rare in patients under 20 years of age, and even rarer in the first decade of life. The present series was investigated to provide recommendations on patient management in terms of therapeutic strategy and follow‐up.

Reliability of ultrasound for the diagnosis of hypertrophic pyloric stenosis

An ultrasound (US) examination might be the best way to study the pylorus and its pathological states once the reliability of this technique has been demonstrated. In order to evaluate the reliability of a sonographic diagnosis of hypertrophic pyloric stenosis (HPS), 17 randomly chosen patients with HPS were examined with both ultrasonography and radiography and then operated on or followed up clinically. Rank correlation between the size and morphological features of the pylorus was found in babies with HPS using US. No false positives or negatives were obtained, and all true positives and negatives were detected. Because of this and the safety of the US technique we wish to emphasize that it should be considered the method of choice in screening infants with severe vomiting. Whenever HPS is suspected from clinical observation, ultrasonography should precede a radiological examination before surgery.

Comparative retrospective study on the modalities of biopsying peripheral neuroblastic tumors: a report from the Italian Pediatric Surgical Oncology Group (GICOP)

Peripheral neuroblastic tumors are the most common extracranial solid neoplasms in children. Early and adequate tissue sampling may speed up the diagnostic process and ensure a prompt start of optimal treatment whenever needed. Different biopsy techniques have been described. The purpose of this multi‐center study is to evaluate the accuracy and safety of the various examined techniques and to determine whether a preferential procedure exists.

Perioperative management of hypertensive neuroblastoma: A study from the Italian Group of Pediatric Surgical Oncologists (GICOP)

BACKGROUND Hypertension (HT) is rarely reported in patients affected by Neuroblastoma (NB), and management guidelines are lacking. Clinical features and perioperative medical treatment in such patients were reviewed to 1) ascertain whether a shared treatment strategy exists among centers and 2) if possible, propose some recommendations for the perioperative management of HT in NB patients. METHODS A retrospective multicenter survey was conducted on patients affected by NB who presented HT symptoms. RESULTS From 2006 to 2014, 1126 children were registered in the Italian Registry of Neuroblastoma (RINB). Of these, 21 with HT (1.8%) were included in our analysis. Pre- and intraoperative HT management was somewhat dissimilar among the participating centers, apart from a certain consistency in the intraoperative use of the alpha-1 blocker urapidil. Six of the 21 patients (28%) needed persistent antihypertensive treatment at a median follow-up of 36months (range 4-96months) despite tumor removal. Involvement of the renal pedicle was the only risk factor constantly associated to HT persistency following surgery. A correlation between the presence of HT and the secretion of specific catecholamines and/or compression of the renal vascular pedicle could not be demonstrated. CONCLUSION Based on this retrospective review of NB patients with HT, no definite therapeutic protocol can be recommended owing to heterogeneity of adopted treatments in different centers. A proposal of perioperative HT management in NB patients is however presented. LEVEL OF EVIDENCE IV.

Proctoneovaginohysterostomy and sigmoid colon pull-through for vaginal agenesis, hematocervicometra, and vestibular anus

Abstract Study Objective: To restore anatomic and functional normality of the perineum and genital system in a pubertal girl aged 12 with pelvic pain and thelarche, vaginal agenesis, cervical hematometra, and vestibular anus. Design: To diagnose the malformation correctly by clinical examination and ultrasonography in order to select the most appropriate surgical treatment. Intervention: Proctoneovaginohysterostomy and sigmoid colon pull-through. Result: The patient is now well with regular, afebrile, painless menstrual cycles. The new vagina is soft and the anal sphincter is continent. Conclusions: Proctoneovaginohysterostomy with sigmoid colon pull-through proved to be an excellent surgical technique for correcting vaginal agenesis, hematocer-vicometra, and vestibular anus.