Beyond image defined risk factors (IDRFs): a delphi survey highlighting definition of the surgical complexity index (SCI) in neuroblastoma.

PURPOSE: Preoperative evaluation of Image Defined Risk Factors (IDRFs) in neuroblastoma (NB) is crucial for determining suitability for upfront resection or tumor biopsy. IDRFs do not all carry the same weighting in predicting tumor complexity and surgical risk. In this study we aimed to assess and categorize a surgical complexity (Surgical Complexity Index, SCI) in NB resection. METHODS: A panel of 15 surgeons was involved in an electronic Delphi consensus survey to identify and score a set of shared items predictive and/or indicative of surgical complexity, including the number of preoperative IDRFs. A shared agreement included the achievement of at least 75% consensus focused on a single or two close risk categories. RESULTS: After 3 Delphi rounds, agreement was established on 25/27 items (92.6%). A severity score was established for each item ranging from 0 to 3 with an overall SCI range varying from a minimum score of zero to a maximum score of 29 points for any given patient. CONCLUSIONS: A consensus on a SCI to stratify the risks related to neuroblastoma tumor resection was established by the panel experts. This index will now be deployed to critically assign a better severity score to IDRFs involved in NB surgery.

In transit metastases in children, adolescents and young adults with localized rhabdomyosarcoma of the distal extremities: Analysis of the EpSSG RMS 2005 study.

In-transit metastases (ITM) are defined as metastatic lymph nodes or deposits occurring between the primary tumor and proximal draining lymph node basin. In extremity rhabdomyosarcoma (RMS), they have rarely been reported. This study evaluates the frequency, staging and survival of patients with ITM in distal extremity RMS. METHODS: Patients with extremity RMS distal to the elbow or knee, enrolled in the EpSSG RMS 2005 trial between 2005 and 2016 were eligible for this study. RESULTS: One hundred and nine distal extremity RMS patients, with a median age of 6.2 years (range 0-21 years) were included. Thirty seven of 109 (34%) had lymph node metastases at diagnosis, 19 of them (51%) had ITM, especially in lower extremity RMS. 18F-FDG-PET/CT detected involved lymph nodes in 47% of patients. In patients not undergoing 18F-FDG-PET/CT lymph node involvement was detected in 22%. The 5-yr EFS of patients with ITM vs proximal lymph nodes vs combined proximal and ITM was 88.9% vs 21.4% vs 20%, respectively (p = 0.01) and 5-yr OS was 100% vs 25.2% vs 15%, respectively (p = 0.003). CONCLUSION: Our study showed that in-transit metastases constituted more than 50% of all lymph node metastases in distal extremity RMS. 18F-FDG-PET/CT improved nodal staging by detecting more regional and in-transit metastases. Popliteal and epitrochlear nodes should be considered as true (distal) regional nodes, instead of in-transit metastases. Biopsy of these nodes is recommended especially in distal extremity RMS of the lower limb. Patients with proximal (axillary or inguinal) lymph node involvement have a worse prognosis.

Omental mesenteric myxoid hamartoma, a subtype of inflammatory myofibroblastic tumor? Considerations based on the histopathological evaluation of four cases.

Omental mesenteric myxoid hamartoma (OMH) is a distinctive myxoid lesion of infancy, characterized by a benign clinical behavior. In the current World Health Organization (WHO) classification of soft tissue tumors, it is considered as part of the morphologic spectrum of inflammatory myofibroblastic tumors (IMT), but this relationship with IMT is still subject to debate. Four lesions with histologic features of OMH occurring in newborns and toddlers are described and compared with classic, ALK-positive IMT. All OMH showed a peculiar dot-like immunostaining for ALK, which, in one of the cases, was cytogenetically found to be associated with an inversion of the ALK gene. While OMHs were positive for smooth muscle actin (SMA), desmin, WT1, podoplanin, and cytokeratins (CAM5.2 and AE1-3), IMT were consistently positive only for SMA (10 cases). ALK-1 displayed cytoplasmic staining in IMT and characteristic paranuclear dot-like staining in OMH.

Bowel parasitosis and neuroendocrine tumours of the appendix. A report from the Italian TREP project.

Five children with a neuroendocrine tumour (NET) of the appendix associated with a parasitic bowel infection are described, and the possibility of inflammation-triggered carcinogenesis is discussed. Schistosoma haematobium is linked primarily to bladder cancer but it has been reported in association with several other histotypes, including NETs of the gastrointestinal tract. Conversely, Enterobius vermicularis has not yet been claimed to participate in the onset of pre-cancerous conditions or tumours. The rare occurrence of contemporary appendiceal NETs and parasitic infection, raises the intriguing hypothesis of an inflammation-related carcinogenesis, although a cause-effect relationship cannot be established. Larger international series of childhood appendiceal NETs, which also include countries with higher prevalence of parasitic bowel infections, are needed to further clarify this possible cause-effect relationship.

Management of symptomatic mesenchymal hamartoma of the chest wall: surgical resection only in symptomatic cases.

Mesenchymal hamartoma of the chest wall (MHCW) is a rare neonatal benign tumor with an estimated incidence of 1 in 3 000 among primary bone tumors, and 1 in one million in the general population. Traditionally, the treatment of choice was an "en bloc" resection, but surgery limited to symptomatic cases, is now suggested by most authors due to the numerous cases of spontaneous regressions. We report 2 patients of symptomatic MHCW, characterized by progressive respiratory distress, who underwent surgical treatment with prompt resolution of symptoms. Surgeons and neonatologists should be aware of this rare condition and its possible fatal or nearly-fatal complications.

Acute splenic torsion in children: which is the best treatment? A case report.

Wandering spleen is a clinical entity which rarely affects children and adolescents. This condition can be asymptomatic or responsible of chronic pain, but it appears as a surgical emergency when an acute twisting occurs. The risk of post-splenectomy sepsis in the pediatric population suggests a conservative approach whenever possible, and also in case of acute torsion, most authors prefer to preserve the spleen and perform a splenopexy. The Authors describe a case of a child with acute splenic torsion, in whom a conservative surgical approach was initially adopted. The conservative option has to be balanced with the risk of prolonged thrombocytopenia, multiple transfusions and a possible second procedure to remove the spleen.

Hematometra in uterus didelphis: a pitfall in teenagers with lower abdominal mass. Report of two cases.

Müllerian malformations represent a wide spectrum of anomaly of the female reproductive tract, usually detected at birth or at puberty. The presence of uterus didelphys and obstructed hemivagina, associated with ipsilateral renal agenesis, is known as Herlyn-Werner-Wunderlich syndrome, a rare congenital anomaly. Two cases of uterus didelphic and hematometra caused by vaginal septum are reported; the girls had a delayed diagnosis due to absence of a specific clinical feature. Clinicians must be aware of the existence of these malformations. An adequate radiological study is mandatory to assess the anatomic conformation, and to optimize the therapeutic procedures.

Liver transplantation for the management of hepatoblastoma.

INTRODUCTION: Hepatoblastoma (HEP) is the most frequent liver malignancy occurring in childhood. Surgical resection currently represents the gold standard for treatment. In patients with initially unresectable tumors, chemotherapy may induce remarkable reductions in size. In nonresponder patients, liver transplantation (OLTx) may offer a chance of cure. MATERIALS AND METHODS: From 1990 to 2003, a total of 400 OLTx (31 pediatric transplants) have been performed at Padua University. Seven patients (4 males and 3 females) underwent OLTx for hepatoblastoma. All patients presented with bilobar liver involvement and had received chemotherapy according to the SIOPEL-1. In all patients preoperative staging was negative for extrahepatic involvement. RESULTS: The mean age of the pts was 8.2 years (range 6.4 months to 34 years). Mean follow-up after OLTx was 41.4 months (median 36, range 3 to 108 months). Actuarial patient survival rates after OLTx for hepatoblastoma are 83.3%, 83.3%, and 56% at 1, 3, and 5 years, respectively. Five of seven subjects with HEP are alive after transplant at 3, 12, 36, 65, and 108 months. Two patients died owing to recurrent disease after 6 and 60 months, respectively, from transplantation. Another subject, primarily treated with surgical resection, shows HEP recurrence at 40 months after OLTx. The remaining 4 patients are alive and well at a mean follow-up of 28 months (median 24, range 3 to 65 months). CONCLUSIONS: Liver transplantation may represent a valid therapeutic option for patients with unresectable HEP, but it is contraindicated in cases of recurrence following previous resection surgery. Neo-adjuvant chemotherapy is of paramount importance to obtain good long-term results.

[Role of mutilating surgery in the treatment of non-chemosensitive pediatric soft tissue sarcomas. Experience of the Italian Cooperative Group Studies RMS-79 and RMS-88]. / Ruolo della chirurgia mutilante nel trattamento dei sarcomi delle parti molli non chemiosensibili in età pediatrica. Esperienza degli studi Cooperativi Italiani RMS-79 ed RMS-88.

UNLABELLED: Aim of the study was to evaluate the role of mutilating surgery in the patients with non chemosensitive soft tissue sarcomas (STS) registered in the Italian Studies. Between 1979 and 1995, 114 patients (pts) with "non chemosensitive" localized STS were enrolled in the cooperative studies RMS-79 (33) and RMS-88 (81). Median age: 89 months (range 1-194). HISTOLOGY: fibrosarcoma 29, Malignant Perpheral Nerve Sheath Tumors (MPNST) 40, malignant fibrous histiocytoma 5, hemangiopericytoma 6, leiomyosarcoma 4, others 20, STS nos 10. The cases were classified according to the IRS staging system as Gr. I 46, Gr. II 24, Gr. III 44. Twelve out of 114 pts (7%), 5/33 (14%) in the first study and 7/81 (8%) in the second, underwent mutilating surgery: 8 pts (of whom 3 were < 2 y of age) had a fibrosarcoma and 4 a MPNST. The mutilating procedure was carried out at diagnosis in 6 cases (4 in RMS-79 and 2 in RMS-and 88) and achieved radicality in 5/6 cases. It was performed after ineffective chemotherapy (CT) in 5 pts (1 in RMS-79 and 4 in RMS-88). One pt (RMS-88) underwent mutilation after multiple local recurrences treated with CT, radiotherapy and conservative excisions (RMS-88) and died. The procedures consisted of 5 amputations, 4 demolitive excisions of extremities with functional impairment, 1 nephrectomy, 1 excision of deferents with spermatic vesicae and 1 mastectomy. OUTCOME: At present 6/12 pts, 5 with fibrosarcoma and 1 with MPNST, are alive with no evidence of disease (NED), 4 of the first and 2 of the second study. Of the 5 Gr. I patients, 4 are alive (NED) and 1 died of 2nd tumor; 1 Gr. II pt is alive NED; of the 5 Gr. III pts 1 is alive NED and 4 died (3 of metastatic spread and 1 of 2nd tumor); the pt amputated after repeated local relapses (Gr. II) is dead of pulmonary metastases. CONCLUSIONS: In the RMS-79 study the mutilations were frequent and were performed at diagnosis in several cases; this trend decreased in the 2nd study in which chemotherapy was attempted in most of the patients. Probably the timing of mutilating procedures was not always adequate (too early or too late). The outcome of pts undergone mutilations is similar to that of the whole group of 114 pts, whose overall survival at 10 years is 64% (C.I. 60-77). Only fibrosarcomas and MPNST probably requires a more aggressive surgical behaviour. At present we avoid initial demolitive surgery; it should be planned without delay after the first local relapse or after initial ineffective CT and RT.

Measures to prevent renal impairment after resection of retroperitoneal neuroblastoma.

Postoperative renal impairment has been reported after kidney-preserving resection of retroperitoneal neuroblastomas (NB). To avoid renal damage, intraoperative procedures include monitoring of central venous pressure (CVP) and diuresis, i.v. administration of electrolyte solutions, mannitol, and furosemide, and local application of lidocaine to the renal vessels. During the first 5 postoperative (p.o.) days, CVP, diuresis, body temperature (T), and lactate dehydrogenase (LDH) levels were monitored; color Doppler ultrasound (CDUS) was also performed on the 7th p.o. day. Simultaneous increases of T (>38.5 degrees ) and LDH (>1,500 IU/l) and/or reduction of urinary flow (< 1.5 ml/kg.h) were indicative of renal damage: in these cases dopamine was administered and CDUS performed. If renal blood flow was normal on CDUS, dopamine was administered for another 2 days; if a vascular thrombosis was detected, fibrinolytic agents (urokinase 4,000 IU/kg bolus and then 4,000 IU/kg.h for 24 h) were utilized. Between May 1997 and June 2000, 29 children (9 F, 20 M, aged) 6-72 months (median 39) affected by grade II inoperable, grade III, and grade IV NB underwent these preventive procedures at the time of surgical excision of the mass after chemotherapy 23 had an uneventful p.o. course. CDUS at 7 days was normal in 22; in 1 (polar resection at operation) it demonstrated a slight reduction of blood flow in the renal cortex. For all 23 patients, the CDUS at 3, 6, and 12 months was negative. Three patients showed a single altered parameter; the CDUS p.o. and during follow-up did not show any alteration. The other 3 patients had two or more altered parameters and were treated with dopamine: in 1 the initial CDUS was normal, but it later showed moderate hypotrophy; in 2 patients a vascular thrombosis was documented. Treatment with urokinase was successful in only 1 patient who had a normalized CDUS after 3 months. The 2nd child developed renal failure and needed hemodyalisis. In our experience, elevation of serum LDH and T and/or oliguria were good indicators of renal impairment. CDUS was also useful in detecting renal blood flow reduction and artery occlusion. These preliminary results show these intra- and postoperative measures to reliably avoid renal impairment in these children. Long-term follow-up could confirm the efficacy of these methods.

Fibrosarcoma in pediatric patients: results of the Italian Cooperative Group studies (1979-1995).

BACKGROUND AND OBJECTIVES: Fibrosarcoma is a rare soft tissue sarcoma (STS) that has two peaks of incidence in pediatric patients: one in infants and young children (infantile fibrosarcoma), another in older children ("adult type" fibrosarcoma). The purpose of this study was to describe the clinical features and the treatment results in patients affected by fibrosarcoma enrolled in two consecutive studies run by the STS-Italian Cooperative Group (ICG) between 1979 and 1995. PATIENTS AND METHODS: Twenty-five evaluable patients were grouped according the intergroup rhabdomyosarcoma staging (IRS) system: 12 Gr I, 5 Gr II, 8 Gr III. The cut-off point between the two forms was considered the age of 2 years: 14 patients were affected by infantile and 11 by adult type of fibrosarcoma. The therapeutic guidelines were not strict and not different for the two forms: patients with initial macroscopic excision (Gr I-II) were given IVA or VAC; Gr III had VAC or VAIA and subsequent excision, if feasible. Radiation therapy (RT) was delivered in patients > 3 years with microscopic (42 Gy) and macroscopic (54 Gy) residuals. RESULTS: Thirteen patients are alive without evidence of disease: 10 in first complete remission (CR), 7 Gr I, 1 Gr II, 2 Gr III, 3 in second CR after local relapse (LR) (2 Gr I, 1 Gr II). Two Gr I patients are alive with metastatic relapse. Nine patients died: six of progressive disease (PD) (three Gr II, three Gr III), two because of a second tumor (one Gr I, one Gr III) and one because of other causes (Gr III). One Gr III patient was lost at follow up, 2 years from diagnosis. The 10 years overall survival (OS) is 67.4% and the progression-free survival (PFS) is 52.2%. The OS for patients < 2 years is 78.6% (11 of 14), versus 51% for patients > 2 years (5 of 11). CONCLUSIONS: The complete excision at diagnosis was the treatment of choice and was related to the best outcome. Microscopical residuals were difficult to treat with chemo-radiotherapy in both forms of fibrosarcoma. Neoadjuvant chemotherapy (CT) obtained a partial remission (PR) only in three of eight cases, while no conclusions concerning the efficacy of CT for infantile forms are possible. Patients < 2 years had a better outcome than the older ones: most of them had a tumor on extremities which was excised at diagnosis.

[Soft tissue sarcoma in childhood: local treatment in patients under 3 years of age. Analysis of the RMS-88 multicenter study]. / Sarcomi delle Parti Molli (SPM) in età pediatrica: trattamento locale nei pazienti sotto i tre anni di età. Analisi dello studio multicentrico RMS-88.

The purpose of this report is to describe the treatment and the outcome of patients affected by soft tissue sarcomas and enrolled in the Italian Cooperative Study RMS 88, whose age was less than 36 months. In particular the role of local treatment is discussed, considering that RT was not recommended by the protocol. The 104 patients, 70 affected by RMS and 34 by NR-STS, were grouped according to the Intergroup Rhabdomyosarcoma Staging (IRS) system. The general guidelines of the study for the local treatment included surgery in Gr I, surgery + radiotherapy (40 Gy) in Gr II, surgery (1 or more procedures) + radiotherapy (45-54 Gy) in Gr III, but RT was not recommended for patients < 3 years. RMS: The 5 patients in Gr I did not receive RT: 4/5 are alive NED and 1 is lost at FU. Among the 5 patients in Gr II, 5 did not receive RT and are alive NED; 4 were given RT and 2 of these died of disease. In the 56 patients in Gr III, RT was utilized in 25: 5 died of disease and 6 manifested distant sequelae due to RT. 10/31 patients who were not given RT, did not undergo any other local treatment and died of disease; 4 patients died after surgery only. NRSTS: 7/9 Gr I patients are alive (1 was treated with RT and did not present sequelae); 1/9 died and 1 is lost at FU. 3/6 Gr II patients are alive (1 after RT), 2 died of disease and 1 is lost at FU. 2/19 Gr III patients were given RT and 1 died of disease; 3 of the not irradiated patients died without any local treatment, 4 after surgery only. CONCLUSION: The local treatment was important for patients' outcome: only 28% of the RMS and 36% of the NRSTS patients who were not treated with surgery a/o RT are in CR. Surgery was not particularly aggressive (6 mutilating procedures). RT was utilized in 33/104 patients and sequelae were 7. The difference in overall survival between patients less than 3 and patients more than 3 is not statistically significant.

Primary re-excision: the Italian experience in patients with localized soft-tissue sarcomas.

Primary re-excision (PRE) is a wide, non-mutilating procedure carried out in patients with soft-tissue sarcomas (STS) when microscopic residuals are left after initial excision or when there are insufficient data on its completeness. The aim of this study was to evaluate the role of PRE in patients enrolled in two consecutive Italian studies between January 1988 and September 1999. Of 126 patients with grade IIa tumors. 53 underwent PRE (23 rhabdomyosarcomas [RMS] and 30 non-RMS STS [NRSTS]). The primary sites were the extremities in 20, paratesticular 15, trunk 9, head-neck-non-parameningeal (HNnPM) 6, bladder 1, other sites in 2; the tumor (T) status was T1a in 30, T1b in 10, T2a in 9, and T2b in 4; the median interval between primary surgery and PRE was 36 days. Of the 53 patients, 45 had complete histologic excision of the tumor (residuals were found in 21/45 specimens) and subsequently received chemotherapy (CT) alone: 39/45 are in their first complete remission (CR) with a median follow-up of 53 months; 6/45 (3 RMS, 3 NRSTS) relapsed, 4 locally (2 extremities, 2 trunk), and 1 of these died of progressive disease, and 2 with metastatic spread died of their disease. In 8/53 cases (HNnPM 4. extremities 2, bladder 1, trunk 1) PRE did not achieve complete removal of the residuals (3 T1a, 2 Tlb, 2 T2a, 1 T2b); these patients were treated with CT and/or radiotherapy (RT); 1 also underwent further surgery. PRE was able to achieve or confirm complete excision in 45/53 patients, and 39 maintained the first CR without RT. The histologic types and the presence of residuals at PRE did not predict the failures; PRE was effective especially in extremity, trunk, and paratesticular sites, whereas its role was uncertain in large sarcomas over 5 cm in size.

Importance of local treatment in pediatric soft tissue sarcomas with microscopic residual after primary surgery: results of the Italian Cooperative Study RMS-88.

BACKGROUND: The goal of primary excision in soft tissue sarcomas is the complete removal of the tumor by a nonmutilating procedure. However, microscopic residuals may be left after a conservative procedure because of inadequate preoperative assessment or difficulties during the operation. The purpose of this report is to describe the treatment and the outcome in patients, enrolled in the Italian Cooperative Study RMS-88, with microscopic residuals after primary excision (IRS Group IIa). PROCEDURE: Microscopic residuals were evident at histology in 52 of 90 patients who had a macroscopic complete primary excision: 25 rhabdomyosarcomas (RMS) and 27 nonrhabdo-soft tissue sarcomas (NRSTS). Eighteen patients were treated with primary reexcision (PRE) and chemotherapy (CT) using VA or IVA regimens; 27 patients received radiation therapy (RT; 40 Gy) and IVA; 7 children in whom PRE was not feasible and RT could not be administered for age <3 years were treated with CT (IVA) alone. RESULTS: Of the 18 patients who underwent a successful PRE + CT, the local relapses were 3 (16.6%); of 27 cases who had RT + CT there were 4 local relapses (14.8%); 3 local relapses occurred in those 7 patients in whom CT alone was administered (43%). CONCLUSIONS: Microscopic residuals after primary surgery were difficult to manage because of the absence of a measurable target. PRE represented the treatment of choice for children <3 years of age who cannot receive RT and for paratesticular sites. PRE and RT showed similar results in achieving local control in extremity and trunk sites, but they could not always avoid local recurrence. In particular PRE was not effective in tumors larger than 5 cm. If microscopic residuals could not be avoided and PRE was not possible, adequate RT was effective both for RMS and for NRSTS.

Nodular regenerative hyperplasia of the liver: description of two cases.

Nodular regenerative hyperplasia (NRH) of the liver is a condition of unknown origin, rarely occurring in children, usually accidentally discovered, described in association with a variety of clinical conditions and drugs. Confusion with other types of hepatic masses may pose a problem and for this reason NRH is considered a "tumor-like lesion." Histologically it consists of single or multiple regenerative foci. Hepatic failure and rupture of the liver have been rarely described as complications in adults, and not in children, and malignant transformation has not been demonstrated. Neither surgical removal nor other treatment is needed. These features are described as they were found in two patients we encountered.

Unusual secondary tumors after childhood lymphoid malignancy.

Second malignant neoplasms (SMN) in individuals who survived childhood cancer have been reported with increasing frequency during the last decades. The overall probability of developing second malignancy for children treated for cancer was estimated at about 2-5% at 25 years. In children, the tumors most often associated with the development of SMN are retinoblastoma and Hodgkin's disease. We report two cases of unusual second tumors in two patients cured of lymphoid malignancy: one boy cured of acute lymphoblastic leukemia developed mediastinal ganglioneuroma nine years later and one girl had gastric carcinoma seven years after Hodgkin's disease. Both developed a tumor in nonirradiated areas. Gastric carcinoma and ganglioneuroma are not reported as recurrent SMN in survivors after childhood cancer, with one single case of gastric carcinoma and one of ganglioneuroblastoma having been reported as second tumor in survivors after childhood cancer.

A simple exam to screen superficial masses: fine-needle aspiration cytology.

Fine-needle aspiration cytology (FNAC) is now considered a useful tool in the evaluation of adult patients with mass lesions. We reviewed the experience with FNAC in our Paediatric Surgical Department. One hundred and eleven FNACs were performed in children with a superficial mass and no definite diagnosis. All the exams were done by the same physician using a fine needle and no anesthesia. We routinely used May-Grüwald-Giemsa and Papanicolaou staining. Patients age ranged from 20 days to 17 years, with a mean age of 6.5 years. A clinically benign pathology was cytologically confirmed in 90 cases (81%). All children did well at follow-up. Malignancy was diagnosed in eight cases (7.2%) and in all was confirmed with a surgical biopsy. In nine children (8.1%) the specimen was considered insufficient for definite diagnosis. In four cases (3.6%) the pathologist diagnosed a possible malignancy that was excluded at surgical biopsy. The sensitivity was 100% and the specificity was 96%. Our experience confirms that FNAC is a fast, cheap, simple, and accurate diagnostic method and should be used for screening in all children with doubtful superficial masses.