Unilateral vasectomy for intractable epididiymo-orchitis in patients with anorectal malformation.

BACKGROUND: Male patients treated for anorectal malformations (ARM) and recto-urethral fistula (RUF) tend to develop recurrent epididymo-orchitis (EO) which occurs approximately in 20% of all them. The optimal management of this condition is unclear because of the extreme its rarity and the unavailability of detailed analysis in literature. To date the majority of this patients benefits from medical treatment and symptoms reduce over time but few data have been published in literature about management of patients with intractable EO. OBJECTIVE: To describe the efficacy of unilateral vasectomy in patients operated on for anorectal malformations with RUF and affected by intractable EO. STUDY DESIGN: We present five patients who met the criteria for intractable EO, and followed at our centre four of whom have undergone unilateral vasectomy. RESULTS: The first episode of EO presented at 42,00 mos ±29.39. Initially, patients were all managed with analgesics and antibiotics. For the failure of therapy, five patients were all offered unilateral vasectomy but only four families accepted procedure. Surgical treatment was performed as a day case without complications. Postoperative follow up was 88,50 mos ±68.36. Prompt and durable resolution of symptoms was observed. DISCUSSION: The long-term effects of recurrent EO in ARM are often underestimated. Prompt and appropriate intervention should prevent this undesirable sequela. Unfortunately, the optimal management of this complication is unclear, partly because of its extreme rarity. The established management needs to follow the route of correcting underlying anomalies and providing long-term analgesic and antibiotics but this may have undesired side effects. We therefore offered families vasectomy for complete symptom resolution and/or drug withdrawal. Vasectomy, as a form of treatment for, can be justified if it can prevent pain, infection and destruction of the testes. Early vasectomy may save enough functional testis tissue. CONCLUSION: To date, the only available treatment to achieve definitive resolution of symptoms in intractable unilateral EO is vasectomy. Long-term effects of such procedure on fertility are unknown. The treatment of recurrent EO in cases without site predilection remains a matter of contention.

Malignant ovarian germ cell tumors in pediatric patients: The AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) study.

OBJECTIVE: Malignant ovarian germ cell tumors (MOGCT) carry an excellent prognosis, and the treatment aims to achieve results with the least possible treatment-related morbidity. The aim of this study was to assess the outcomes of pediatric patients with MOGCT. METHODS: Patients were treated according to their stage: surgery and surveillance for stage I; a modified bleomycin-etoposide-cisplatin (BEP) regimen for stages II (three cycles), III, and IV (three cycles) with surgery on residual disease. RESULTS: Seventy-seven patients were enrolled (median age 11.8 years), 26 with dysgerminoma (Dysg), 13 with immature teratoma and elevated serum alpha-fetoprotein levels (IT + AFP), and 38 with nondysgeminoma (Non-Dysg) staged as follows: 27 stage I, 13 stage II, 32 stage III, 5 stage IV. Among evaluable patients in stage I (5-year event-free survival [EFS] 72.1% [95% CI: 56.4-92.1%]; 5-year overall survival [OS] 100%), seven relapsed (three patients with Dysg and four patients with Non-Dysg) and were rescued with chemotherapy (plus surgery in three patients). Among the evaluable patients with stages II-IV, 48 (98%) achieved complete remission after chemotherapy ± surgery, one (IT + AFP, stage IV) had progressive disease. In the whole series (median follow-up 80 months), the 5-year OS and EFS were 98.5% (95% CI: 95.6-100%) and 84.5% (95% CI: 76.5-93.5%). CONCLUSIONS: We confirm the excellent outcome for MOGCT. Robust data are lacking on surgical staging, surveillance for Non-Dysg with stage I, the management of IT + AFP, and the most appropriate BEP regimen. As pediatric oncologists, we support the role of surveillance after proper surgical staging providing cases are managed by experts at specialized pediatric centers.

Prevalence of pain in the departments of surgery and oncohematology of a paediatric hospital that has joined the project "Towards pain free hospital".

BACKGROUND: Among hospitalized adults and children pain is undertreated. This study wants to assess the effectiveness of pain therapy in two departments of a large children's hospital. MATERIALS AND METHODS: During a single day work three committees, administering a questionnaire to patients or parents, have evaluated the adherence to international recommendations (JCI and WHO) in the management of analgesic therapy. Patient demographics, prevalence and intensity (moderate and/or severe) of pain (during hospitalization, 24 hours before and at the time of the interview), analgesia (type, route, duration and frequency of administration) and Pain Management Index (=analgesic score-pain score) were recorded. RESULTS: 75 patients participated in the study (age: 2 months up to 24 years, mean 7.8 ± 6). During hospitalization 43 children (57%) had no pain while 32 (43%) have experienced pain. 22 children (29 %) had pain 24 hours before and 12 (16%) at the time of the interview. The average value of the PMI was -0.8±1.3 with a minimum of -3 and a maximum of +2: 60% (19) of the children had a PMI less than 0 (undertreated pain) while 40% (13) had a value=or>0. Out of 32 patients who needed an analgesic therapy 14 (44%) received an around-the-clock dosing, 8 (25%) an intermittent therapy and 10 (31%) no treatment.17 (77 %) were the single drug therapy and 5 (23%) the multimodal ones. CONCLUSIONS: The prevalence of pain in the two departments is high. The main cause is that knowledge is not still well translated into clinical practice.

Surgical management of papillary thyroid carcinoma in childhood and adolescence: an Italian multicenter study on 250 patients.

PURPOSE: The extent of surgery for pediatric papillary thyroid carcinoma is debatable. The aim of this study was to evaluate the feasibility of offering pediatric patients a tailored surgical approach based on certain clinical features. METHODS: A national multicenter retrospective review of 250 pediatric patients treated for papillary thyroid carcinoma in a 14-year period was performed. Outcomes of interest included tumor-related features, type of surgery, surgical morbidity, disease-free and overall survival rates. Recurrence was thoroughly analyzed with particular focus on how it correlated with certain patient- and tumor-related features. RESULTS: The majority of patients (58.8 %) had tumors >2 cm in size. Nodal involvement occurred in 115/250 (46 %) patients and distant metastasis in 4 % (10/250). Total thyroidectomy and lobectomy were performed in 90.4 % (226/250) and 9.6 % (24/250) of patients, respectively. The overall rate of surgical complications was 20.8 % (52/250). These included transient and permanent hypoparathyroidism (13.6 and 4.4 %, respectively), and vocal fold palsy (2.8 %). All surgical complications occurred exclusively in the total thyroidectomy group. The rate of recurrent disease was 12 % (30/250) with the vast majority of recurrences (96.6 %) occurring in the total thyroidectomy group. The risk of recurrence correlated significantly with certain tumor-related features (size > 2 cm, multifocality, extrathyroidal invasion, nodal positivity, and distant metastasis). However, it did not correlate with the patient's age or sex. Overall survival was 100 %. CONCLUSION: Pediatric patients are likely to benefit from a tailored surgical strategy. Uniformly offering patients total thyroidectomy seems to be an overly radical approach.

Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition.

The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1ß and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota-inflammasome-brain axis may offer novel therapeutic targets for psychiatric disorders.

The Polycomb group (PcG) protein EZH2 supports the survival of PAX3-FOXO1 alveolar rhabdomyosarcoma by repressing FBXO32 (Atrogin1/MAFbx).

The Polycomb group (PcG) proteins regulate stem cell differentiation via the repression of gene transcription, and their deregulation has been widely implicated in cancer development. The PcG protein Enhancer of Zeste Homolog 2 (EZH2) works as a catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) by methylating lysine 27 on histone H3 (H3K27me3), a hallmark of PRC2-mediated gene repression. In skeletal muscle progenitors, EZH2 prevents an unscheduled differentiation by repressing muscle-specific gene expression and is downregulated during the course of differentiation. In rhabdomyosarcoma (RMS), a pediatric soft-tissue sarcoma thought to arise from myogenic precursors, EZH2 is abnormally expressed and its downregulation in vitro leads to muscle-like differentiation of RMS cells of the embryonal variant. However, the role of EZH2 in the clinically aggressive subgroup of alveolar RMS, characterized by the expression of PAX3-FOXO1 oncoprotein, remains unknown. We show here that EZH2 depletion in these cells leads to programmed cell death. Transcriptional derepression of F-box protein 32 (FBXO32) (Atrogin1/MAFbx), a gene associated with muscle homeostasis, was evidenced in PAX3-FOXO1 RMS cells silenced for EZH2. This phenomenon was associated with reduced EZH2 occupancy and H3K27me3 levels at the FBXO32 promoter. Simultaneous knockdown of FBXO32 and EZH2 in PAX3-FOXO1 RMS cells impaired the pro-apoptotic response, whereas the overexpression of FBXO32 facilitated programmed cell death in EZH2-depleted cells. Pharmacological inhibition of EZH2 by either 3-Deazaneplanocin A or a catalytic EZH2 inhibitor mirrored the phenotypic and molecular effects of EZH2 knockdown in vitro and prevented tumor growth in vivo. Collectively, these results indicate that EZH2 is a key factor in the proliferation and survival of PAX3-FOXO1 alveolar RMS cells working, at least in part, by repressing FBXO32. They also suggest that the reducing activity of EZH2 could represent a novel adjuvant strategy to eradicate high-risk PAX3-FOXO1 alveolar RMS.

Association between gastroesophageal reflux and endobronchial carcinoid: a case report.

Children with neurological disorders may suffer from gastroesophageal reflux disease (GERD). Typical symptoms are vomiting, regurgitation and hematemesis. Patients present with respiratory symptoms only in cases with swallowing disorders causing chronic airway aspiration. We report the case of a patient affected by chromosome 8 p deletion syndrome with mental retardation, referred to our unit for suspected GERD. Chest X-ray, performed at admission for coexisting respiratory complaints, showed left lower lobe pneumonia; esophageal pH monitoring and upper endoscopy were normal for GERD. To rule out chronic airway aspiration, gastroesophageal 99 mTc scintigraphy with lung scan 18 to 24 h after a test meal and video fluoroscopy swallowing study were performed, both negative. Two months later, a second episode of left lower lobe pneumonia occurred. A chest CT scan was performed and showed an endobronchial mass; the biopsy taken during the broncoscopy was not conclusive. Surgical excision resulted in a diagnosis of pulmonary carcinoid. Bronchial carcinoids, although rare, should be taken into consideration as a potential cause of recurrent pneumonia even in the presence of demonstrated GERD where severe respiratory infections only occur with coexisting chronic pulmonary aspiration, even in neurologically impaired people.

Minimally-invasive surgery in paediatric oncology: proposal of recommendations.

The Authors report a proposal of recommendations concerning Minimally Invasive Surgery (MIS) in Paediatric Oncology. Since the exact role of MIS in Paediatric Oncology is still not completely defined, a restrict panel of Italian Paediatric Surgeons, some interested in Oncologic Surgery, others in MIS, prepared a schematic document, mainly founded on literature data, to provide Paediatric Surgeons with recommendations useful to approach paediatric tumours with MIS. The final draft was approved by the Italian Group of Paediatric Oncologic Surgeons. The Authors summarize the feasibility of MIS, when performed with different purposes (biopsy / resection) and timing (initial / delayed surgery) for the most common solid tumours in children. The oncologic criteria must be always followed with MIS as well as with "open" surgery.

Elevated serum alpha-fetoprotein in Wilms tumor may follow the same pattern of other fetal neoplasms after treatment: evidence from three cases.

Alpha-fetoprotein (AFP) is a common tumoral marker in pediatric neoplasms; increased serum levels are usually encountered in tumors arising from tissues producing AFP during fetal life. However, elevation of such protein is rarely found in patients with Wilms tumor (WT). Three patients with WT and elevated serum AFP were studied over the course of the disease. One patient had left WT with invasion of aorto-caval lymph nodes and lung metastases. The second patient was referred to our center for abdominal recurrence of bilateral WT whereas the third showed right WT with inferior vena cava thrombosis. AFP levels demonstrated a trend parallel to decrease/increase of tumor size, with further elevation in patients with metastases. Elevated AFP serum levels in patients with WT could be related to peculiar histological features and serial dosage might be a useful diagnostic and prognostic test.

Ifosfamide/carboplatin/etoposide (ICE) as front-line, topotecan/cyclophosphamide as second-line and oral temozolomide as third-line treatment for advanced neuroblastoma over one year of age.

Children affected by advanced neuroblastoma have a discouraging prognosis, but intensive induction chemotherapy may increase the complete response rate. The combination of ifosfamide, carboplatin and etoposide (ICE) was used for the first time as front-line regimen in patients with stage 4 neuroblastoma over the age of 1 y. Similarly, second-line treatment for children with relapsed neuroblastoma, particularly after high-dose chemotherapy, has been unsatisfactory. The combination of topotecan and cyclophosphamide was studied in resistant or relapsed solid tumors. Furthermore, there is a need for effective palliative treatment in patients failing therapy. Temozolomide, a new dacarbazine analog with optimal oral bioavailability, is being used in an ongoing phase II study as an alternative to oral etoposide. Seventeen patients with stage 4 neuroblastoma have entered the ICE study; 15/16 (94%) major responses after induction were observed and 6/16 (37%) evaluable patients are disease free after a median of 51 mo. Twenty-one patients with relapsed/refractory disease (of whom 13 neuroblastomas) entered the topotecan/cyclophosphamide study: 7/21 (33%) patients responded. Forty-one patients entered the temozolomide study (of whom 16 had neuroblastomas): stable disease and symptom relief were obtained in 15/30 (50%) evaluable patients. Intensive induction with ICE resulted in a faster response with high response rate; a larger study with longer follow-up is needed to confirm a survival advantage. Second-line treatment was effective in obtaining remissions, some of them long lasting. Third-line treatment did not elicit measurable responses in neuroblastoma, but achieved prolonged freedom from disease progression and excellent palliation in several patients.

A single-institution Wilms' tumor and localized neuroblastoma series.

Since January 1980, 120 children affected by Wilms' tumor have been treated at Bambino Gesù, mostly with multimodality treatment according to Société Internationale d'Oncologie Pediatrique (SIOP) protocols, including chemotherapy, surgery and radiotherapy in selected cases. This treatment approach emphasizes the role of preoperative (neoadjuvant) chemotherapy as opposed to the approach favored by the National Wilms' Tumor Study, which is focused on optimizing postoperative chemotherapy after primary surgery. Thus, using SIOP guidelines, staging occurs at the time of surgery, after chemotherapy administration. These differences will constitute the baseline for a comparison between the two experiences. Bilaterality, nephroblastomatosis, partial nephrectomy in unilateral Wilms' tumor and thrombosis of the vena cava are the main topics discussed. For the present study, the analysis was restricted to 98 consecutive cases diagnosed until December 1999, for whom at least 24 mo of follow-up is available. The more recent experience of treating resectable neuroblastoma in cooperative studies dates back to 1979, when the first Italian Cooperative Group Neuroblastoma protocol was introduced. This experience was continued within the frame of the first Localized Neuroblastoma European Study Group protocol (LNESG 94), and will be compared to North American Cooperative Group approaches and outcomes. Preoperative evaluation of surgical risk factors, intraoperative complications and their management, and long-term outcome will be discussed.

Neurovesical dysfunction in children after treating pelvic neoplasms.

OBJECTIVE: To evaluate 10 years of experience, and thus define the occurrence and causes, of neurogenic lower urinary tract dysfunction in children with pelvic neoplasms treated by surgery. PATIENTS AND METHODS: From 1991 to 2000, 33 children were operated by the same surgeons for pelvic neoplasms; 11 were analysed, comprising four each with sacrococcygeal teratoma (ST) and ganglioneuroma, and one each with yolk sac tumour (YST), neuroblastoma and myofibroblastic bladder sarcoma (MBS). The other patients were not assessed because eight had died or were in severe progression, three were treated by bladder substitution and the others were lost to follow-up or refused a urological evaluation. All 11 children were evaluated at >/= 6 months after surgery with a questionnaire about bowel and voiding habits, a neurological and orthopaedic assessment, a noninvasive urodynamic study, renal ultrasonography and spinal and pelvic magnetic resonance imaging (MRI). All patients with signs of bladder dysfunction were evaluated by a pressure-flow study. The results were analysed for surgical approach and anatomical involvement, i.e. group A, extensive surgery for complete tumour excision in the sacral area (ST and YST); group B, surgery for tumour resection in the paraspinal ganglia area (neuroblastoma and ganglioneuroma); and group C, bladder tumour with partial bladder resection (MBS). RESULTS: Eight patients had signs or symptoms related to bladder sphincter dysfunction. One child refused the invasive urodynamic evaluation, leaving seven for analysis (two each ST and ganglioneuroma, one each YST, neuroblastoma and MBS). The urodynamic findings were normal in three children. On spinal and pelvic MRI a presacral lipoma with syringomyelia was discovered in one child with ST. Eight children had bladder dysfunction and two had no neurogenic damage (which was only in sacral tumours); in one child it was related to an upper motor neurone lesion from spinal dysraphism and in the other to a lower motor neurone lesion from surgical injury to the splanchnic nerves. Patients operated for paraspinal tumours had more bladder dysfunction but no signs of neurogenic damage, as did the patient with partial bladder resection. However in Group B, there may have been a transient or incomplete nerve injury in one patient. CONCLUSIONS: Deficits of parasympathetic, sympathetic and somatic innervation of the bladder and the urethra may occur in children after surgery for pelvic neoplasms, related to minor or major surgical trauma. In ST, a tethered cord may be associated with mixed neurogenic damage. Knowledge of bladder dysfunction in anorectal malformations, spinal dysraphism, etc. and the clinical protocol used in these patients also seemed to be useful for understanding the development of voiding dysfunction in patients with neoplasm.

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.

Glutathione transferase P1 polymorphism in neuroblastoma studied by endonuclease restriction mapping.

Several members of the different glutathione transferase (GST) gene classes are polymorphic. Particular interest has been focused on the GSTP class because this gene class is up-regulated during the early stage of oncogenesis and is significantly overexpressed in many human tumors. It has also been shown that high levels of GSTP1 expression are associated directly with tumor drug resistance and with poor patient survival. Our aim was to understand the possible association between GSTP1 polymorphism and cellular response to chemotherapeutic drugs in neuroblastoma. In fact, several antineoplastic drugs used in the neuroblastoma high-risk chemotherapeutic protocol are potential substrates of GSTP1-1 (etoposide, adriamycin and carboplatin). The GSTP1 genotype homozygote *A/*A was identified in 11 patients independent of their response to the chemotherapeutic treatment. Only four patients had a heterozygote genotype A*/B*. Therefore, based on our preliminary data, we were not able to conclude that GSTP1 polymorphism had an impact on patient response to treatment in neuroblastoma.

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.

Prenatal diagnosis of a bronchogenic cyst in an unusual site.

We report a rare case of a subdiaphragmatic cyst, diagnosed prenatally during routine ultrasound screening at 25 weeks' gestation. Serial ultrasonographic evaluation demonstrated a slight increase in the size of the cyst during pregnancy. On the basis of the anatomic site and the sonographic features of the lesion, four diagnostic hypotheses were postulated: cystic neuroblastoma, adrenal hemorrhage, duplication of the inferior third of the esophagus and retroperitoneal cystic lymphangioma. A healthy baby, weighing 3300 g and with Apgar scores of 8 and 9, was delivered vaginally at term. He underwent successful surgery at the age of 3 months. The post-operative course was uneventful and the baby is currently doing well. Histology revealed a bronchogenic cyst.

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.

Cystic adenomatoid malformation of the lung: clinical evolution and management.

UNLABELLED: Cystic adenomatoid malformation of the lung (CAML) is a rare pulmonary maldevelopment resulting from an abnormal growth of the terminal bronchial structures. This study proposes a possible management of prenatally diagnosed CAML. A group of nine cases of CAML diagnosed prenatally between January 1990 and December 1995 was studied retrospectively. The evolution of lesions was followed in utero by serial ultrasound monitoring. Chest X-ray was performed at birth in all neonates and CT only in the symptomatic ones. CAML was macrocystic in three cases and microcystic in six. No polyhydramnios, hydrops or associated malformations were seen. In four cases, CAML was confirmed at birth and required surgery. The lesion decreased in size prenatally in five fetuses, of whom only one underwent surgery. In two further cases a prenatal diagnosis of CAML was changed to diaphragmatic hernia. CONCLUSION: Given the possible clinical disappearance or resolution of cystic adenomatoid malformation of the lung, we believe that surgery is justified at birth only in symptomatic and radiologically positive neonates. It could be safely delayed in those asymptomatic patients with either positive or negative chest X-ray. The former need computed tomography at birth, whereas, in the latter, it should be performed at 6 months of age for a more definitive assessment of the patient.