Salvage treatment for children with relapsed/refractory germ cell tumors: The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience.

BACKGROUND: Malignant germ cell tumors (GCTs) are a heterogeneous group of rare neoplasms in children. Optimal outcome is achieved with multimodal therapies for patients with both localized and advanced disease, especially after the introduction of platinum-based chemotherapy regimens. In this respect, data on salvage treatment for children with relapsed or platinum-refractory disease are still limited. METHODS: Retrospective analysis of data regarding patients affected by malignant GCTs with platinum-refractory or relapsed disease after first-line treatment according to AIEOP TCGM 2004 protocol was conducted. RESULTS: Twenty-one patients, 15 females and 6 males, were considered for the analysis. All 21 patients received second-line conventional chemotherapy (SLCT), two of these immediately after surgery for local relapse removal. Two patients showed a progression of disease during SLCT and died of disease shortly thereafter, whereas 19 patients were in partial remission (PR) or complete remission (CR) after SLCT. Treatment after SLCT consisted in surgery on residual tumor mass (9/19) followed by high dose of chemotherapy (HDCT) with autologous hematopoietic stem cell support (16/19). The overall survival (OS) and event-free survival of the whole populations are 71% and 66.6%, respectively. Platinum-refractory patients OS is 54.5% compared with 91.5% of the relapsed group. There were no treatment-related deaths. CONCLUSION: SLCT followed or not by HDCT is an effective salvage treatment for children with relapsed/refractory GCTs. However, the role of HDCT following SLCT needs to be further investigated, especially regarding the identification of specific patient subgroups, which can benefit from this more intensive treatment.

Mature and immature teratoma: A report from the second Italian pediatric study.

BACKGROUND: Teratomas demonstrate a benign clinical behavior, however they may recur with malignant components or as teratoma, and in a small group of patients prognosis could be fatal. After the first Italian study, we collected cases of teratoma, alongside the protocol for malignant germ cell tumors. PROCEDURE: Patients with teratoma were collected from 2004 to 2014. Teratomas were classified according to the WHO classifications, as mature and immature. Patients with pathological aFP and/or bHCG, and those with a malignant germ cell component were not included. RESULTS: The study enrolled 219 patients (150 mature, 69 immature teratomas) with a median age at diagnosis of 42 months. The primary sites involved were: 118 gonadal and 101 extragonadal teratomas. Two females with ovarian teratoma had a positive family history. Complete and incomplete surgeries were performed in 85% and 9% of cases. Seventeen events occurred: six females had a second metachronous tumor (5 contralateral ovarian teratoma, 1 adrenal neuroblastoma) and 11 teratomas relapsed/progressed (3 mature, 8 immature teratomas). Two patients died, one of progressive immature teratoma and one of surgical complications. At a median follow up of 68 months, the event-free, relapse-free, and overall survival rates were 90.6%, 94.3%, 98.6%, respectively. CONCLUSIONS: Teratomas show a good prognosis, especially the mature ones: surgery and follow-up remain the standard approach. Incomplete surgery in immature teratoma is the group at greatest risk of relapse. Bilateral ovarian tumors are a possibility, and the rare family predisposition to ovarian mature teratoma warrants further analyses.

Predictive factors of abdominal compartment syndrome in neonatal age.

In the pediatric population, abdominal compartment syndrome (ACS) is a known complication of abdominal wall defect repair. However, there are only few reports on ACS in newborns and only a proposal of critical intra-abdominal pressure value (IAP) in term newborns, absent in preterm newborns. Although the prevalent clinical sign is tense abdominal distension, it may be difficult to distinguish ACS from pathologies that will not require decompression. The purpose of this study was to identify predictors for ACS and therefore morbidity or mortality indicators. We reviewed newborns presenting with tense abdominal distension and end organ failure. Anamnestic, clinical, laboratory, and instrumental investigations were analyzed to extrapolate predictors. Outcomes were compared with a control group. The incidence of ACS in our neonatal intensive care unit was 5% in the overall population of babies, 16% in tracheal-ventilated newborns, and 57% in infants with abdominal wall defects. We found that, with onset of acidosis or high gastric residuals, the lactate values will be predictive for mortality. We can also suggest paying particular attention to high lactate values just at the onset of distension, in infants with more advanced gestational age, with previously surgical repair, to determine early surgical intervention independently of a specific IAP measurement.

Teratoma with a malignant somatic component in pediatric patients: the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience.

BACKGROUND: Teratoma with a malignant somatic component (TMSC) is rare but described in adults, whereas information on pediatric presentation is sparse. PROCEDURE: The Associazione Italiana Ematologia Oncologia Pediatrica identified 14 cases of TMSC. Clinical files and pathology specimens were reviewed. RESULTS: The series (9 female, 5 male) showed the following disease: testis (2), sacrococcygeal (3), ovary (3), retroperitoneum (3), mediastinum (2), and foot soft tissue (1). Distribution of the somatic component was: carcinoma (4), pancreatic neuroendocrine tumor (1), neuroblastoma (3), rhabdomyosarcoma (3), rhabdomyosarcoma plus liposarcoma, chondrosarcoma, neurogenic sarcoma (1), chondrosarcoma plus neuroectodermal sarcoma (1), malignant peripheral nerve sheath tumor (1). Three patients were in stage I, four in stage II, three in stage III, and four in stage IV. All but one patient underwent surgery and only females showed carcinoma components. Nine patients relapsed or progressed and eight died. Six patients are alive and disease-free. Two patients underwent complete resection and four were treated based on transformed histologies. Relapse-free and overall survival rates were 35.7% and 42.8%, respectively (median follow-up, 31 months). CONCLUSIONS: Prognosis for germ cell tumors (GCTs) containing MSC is worse than that for GCTs. The pediatric disease appears to be more heterogeneous in tumor site distribution and MSC histology than in adults. Our series suggests no effects of age, histology, or gender on outcome. Surgery has an essential role in localized disease, with complete resection highly desirable. Chemotherapy optimized for histology should include reagents directed to the somatic malignancy, if chemosensitive. Malignant GCT warrants GCT-directed chemotherapy.

Malignant testicular germ cell tumors in children and adolescents: The AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) protocol.

OBJECTIVES: We report the results of an Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) study on the treatment of testicular germ cell tumors (TGCT) with a pediatric PEB (pPEB) regimen (cisplatin 25 mg/m2 daily on days 1-4; etoposide 100 mg/m2 daily on days 1-4; bleomycin 15 mg/m2 on day 2, once per cycle). METHODS AND MATERIALS: Male patients under 18 years old with malignant TGCT were enrolled for a second national prospective protocol. All patients underwent orchiectomy at diagnosis. Those with Stage I received no chemotherapy; those with Stage II-III disease received three cycles of pPEB; and those with Stage IV received four cycles. After chemotherapy, resection of radiologically-evident residual disease was recommended. The main study end-points were overall survival and relapse-free survival. RESULTS: Ninety-nine boys from 0.5 to 17.8 years old (median 15.4 years) were evaluable, and staged as follows: 58 Stage I (59%), 7 Stage II (7%), 14 Stage III (14%), and 20 Stage IV (20%). With a median follow-up of 59 months (range 4-165 months), 5-year relapse-free survival (95% CI) was 73% (65%-83%) for the whole sample, 65% (53%-79%) for Stage I patients, and 86% (75%-98%) for Stage II-IV patients. Five-year overall survival (95% CI) was 99% (97%-100%). CONCLUSIONS: We confirmed a good prognosis for malignant TGCT in children and adolescents. Reducing the number of chemotherapy cycles for Stage II-III disease does not seem to negatively affect survival outcomes.

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.

Fibrous hamartoma of infancy: an Italian multi-institutional experience.

BACKGROUND: Fibrous hamartoma (FH) of infancy is a benign mesenchymal tumor, occurring as a superficial mass. Complete excision is curative. OBJECTIVE AND METHODS: The clinical features and treatment results of 18 children with FH are described. RESULTS: Local excision was the most common procedure. Surgery was radical in 10 patients, with microscopic residual disease in 6; all of them are alive with no evidence of disease 2 to 49 months after diagnosis. One patient, treated with a local reexcision for macroscopic residual disease (and chemotherapy for a synchronous desmoid fibromatosis) is well 83 months after diagnosis; the last patient, with a lesion of the labia majora, only underwent biopsy and is doing well, awaiting plastic surgery. LIMITATIONS: The results did not reach statistical significance due to difficulties in collecting cases. CONCLUSIONS: FH should be treated by complete excision; in our experience a nonradical excision was also able to achieve the cure. An aggressive approach should be avoided, as the overall prognosis is excellent.

Corrigendum to "Multiple Congenital Colonic Stenosis: A Rare Gastrointestinal Malformation".

[This corrects the article DOI: 10.1155/2016/6329793.].

Solitary Myofibroma of the Bladder Trigone in a 3-Month-Old Patient: First Case Report.

Visceral solitary myofibromas are uncommon in childhood. We report a case of a solitary asymptomatic visceral myofibroma of the bladder trigone occurring in a 3-month-old boy. Once malignancies were ruled out by cystoscopy, radical excision was performed in order to avoid any potential impairment of bladder dynamic. Postoperative course was uneventful and patient was discharged on day 3 after surgery. After 36 months of follow-up, the patient is toilet-trained and remains well; bladder function is normal.

An Uncommon Case of Adolescent Ovarian Teratoma Incarcerated in Inguinal Hernia.

Mature cystic teratoma is the most frequent benign ovarian neoplastic lesion in adolescents and is generally composed of fully differentiated tissue arising from multipotential three germinal layers. It accounts for approximately 50% of benign ovarian tumors in childhood. Rarely, a bilateral, synchronous, or metachronous presentation can be observed, supporting a conservative approach as the first surgical approach. We report a case of an ovarian mature cystic incarcerated in indirect inguinal hernia in a 15-year-old girl undergoing ovary-sparing surgery. To our knowledge this is the first case of such lesion incarcerated in an inguinal hernia reported in literature.

Splenogonadal Fusion: A Genetic Disorder?-Report of a Case and Review of the Literature.

Splenogonadal fusion is a rare congenital anomaly in which there is fusion between the spleen and gonad, epididymis or vas. We treated a patient with scrotal mass. A discontinuous fusion between the spleen and epididymis was found: after frozen section mass was excised sparing testis. Although rare, the splenogonadal fusion should be considered in the differential diagnosis of scrotal masses in children, and orchiectomy should be avoided. Moreover, examination of siblings showed a brother affected from accessory spleen. This finding, not reported previously to our knowledge, suggests a possible familiarity of this disorder.

Mature and immature teratomas: results of the first paediatric Italian study.

Teratoma is the most common germ cell tumour in childhood; mature (MT) and immature teratomas (IT) are benign tumours, but if they recur, they can be in some cases malignant. The aim of this paper is to evaluate Italian patients with MT and IT enrolled from 1991 to 2001, in a prospective multicentric study. One hundred and eighty-three patients, observed in 15 Italian Centers of Paediatric Oncology and three Paediatric Surgical Units were enrolled. Clinical data, treatment and results were all analysed. Initial evaluation and subsequent follow up included clinical examination, tumour markers and imaging procedures. Surgical resection was recommended for all the tumours. Histology was centrally reviewed and IT was classified as grading 1-3. Chemotherapy (CT) with Vinblastine, D: -actinomycin and cyclophosphamide was indicated for extra-testicular IT grade 2 or 3. MT was diagnosed in 127 patients (93 F and 34 M, age 1-192 months, median 24): 58 patients had gonadic tumour (23 testicular, 35 ovaric), 69 extragonadic (45 sacrococcygeal, 11 mediastinic, 7 retroperitoneal, 6 in other sites). A complete resection was performed in 117 patients, a partial resection in eight patients and biopsy in one. IT was diagnosed in 56 patients (34 F, 22 M, age 1-168 months, median 7). The T grading was 1 in 14 cases, 2 in 26, 3 in 16; 28 had gonadic T (17 ovary, 11 testis), 28 extragonadic (sacrococcygeal 19, mediastinic 3, retroperitoneal 2, other sites 4). CT was administered in eight patients; 15/182 patients relapsed (1 in a metastatic site) and in 5/15 the relapse showed malignant histology. Seven MT (5.5%) relapsed (five sacrococcygeal, one retroperitoneal, one mediastinic): surgery at diagnosis had been complete in five and with residual in two; the relapse was malignant in two patients with sacrococcygeal (sc) tumours, who had a complete resection and a partial resection respectively. Eight IT (14.2%) relapsed (four ovary, three sc, one retroperitoneal). The initial surgical resection had been complete in one, with residual in six, and a biopsy had been performed in one. A malignant recurrence occurred in two patients with sc tumours (after partial resection in one and after biopsy + CT in one) and in one patient with ovarian IT after a partial resection. All the patients underwent surgical excision of the recurred mass; CT according to Protocol for Malignant GCT was administered to those who had malignant recurrence; 122/126 patients with MT and 53/56 with IT are alive without disease with a follow up of 8-144 months (median 56). Two patients with malignant relapse (one with sc MT, one with sc IT) died because of the progression of the disease. Another two died due to severe malformations (one MT, one IT) and three were lost to follow up (two MT, one IT). The overall survival (OS) at 10 years is 98% (95% CI 93.9-99.4); the event free survival (EFS) is 90.4% (95 CI 84.8-94.0). At Cox analysis no significant difference in EFS was found regarding age and site of the primary tumour, while females (P = 0.011), patients with grade 1-3 histology (P = 0.025) and patients with incomplete resection appeared at higher risk of death or relapse (P < 0.001), with a seven, three and eightfold increase in risk, respectively. Our data showed that incomplete resection and female gender are important risk factors for relapse or death, more so than IT histology. The number of patients treated with CT is not sufficient to evaluate the efficacy of CT in avoiding malignant relapse.

Congenital hepatic mesenchymal hamartoma associated with mesenchymal stem villous hyperplasia of the placenta: case report.

A newborn with an unusual association of hepatic mesenchymal hamartoma and mesenchymal stem villous hyperplasia of the placenta is presented. At birth, the large hepatic mass caused severe respiratory distress necessitating early surgical intervention. This report on the association of hepatic mesenchymal hamartoma and mesenchymal stem villous hyperplasia of the placenta strongly suggests a common pathogenetic origin of the 2 lesions.

Malignant germ cell tumors in childhood: results of the first Italian cooperative study "TCG 91".

BACKGROUND AND AIMS: About 20% of patients with germ cell tumor (GCT) are still resistant to therapy. To investigate which features are present in resistant patients, a multicenter study on GCT in children was undertaken to correlate clinical and laboratory parameters with the outcome. METHODS: Patients aged less than 16 years, with histologically proven extracranial GCT were included. RESULTS: Ninety-five patients (median age 33 months, 45 males) were eligible. The site of the primary tumor was gonadal in 59, extragonadal in 36. The stage was I in 39; II in 5; IIIa (microscopic residue) in 7; IIIb (macroscopic residue) in 16; IIIc (unresectable) in 13; IV in 15. The treatment was surgery alone in 31; surgery plus radiotherapy in 1; chemotherapy +/- surgery in 63. Post-chemotherapy resection in 19 (10 complete, 9 partial). The chemotherapy regimen was carboplatin 400 mg/m2/day on days 1, 2; etoposide 150 mg/m2/day on days 1, 2; ifosfamide 1,500 mg/m2/day on days 21, 22; dactinomycin 1.5 mg/m2/day on day 21; vincristine 1.5 mg/m2/day on day 21. Three patients died because of toxicity and two non-responders (to primary chemotherapy), died of progression; among the remaining 90 patients 20 relapsed, 9 are in second remission, 2 are alive with disease, and 9 died of disease progression (one from progression and intracranial hemorrhage). Overall survival was 82.7% and event-free survival: 71.5%. Survival according to: (a) site: testis: 100%; ovary: 88%; sacrococcyx: 69.6%; other sites: 33.3% (P < 0.001); (b) stage: I and II: 100%; IIIa: 83.3%; IIIb: 84.6%; IIIc: 60.6%; IV: 53.2% (P < 0.001); (c) AFP levels: normal: 85.5%; 42-9,470 ng/ml: 84.6%; >/=10,000 ng/ml: 58.7% (P = 0.02). All the pts who had complete resection of the primary tumor at diagnosis or at delayed surgery, remained in remission. CONCLUSIONS: Multivariate analysis showed that the primary site of tumor was the only independent prognostic factor for survival and EFS.

Role of surgery for nonmetastatic abdominal rhabdomyosarcomas: a report from the Italian and German Soft Tissue Cooperative Groups Studies.

BACKGROUND: In the current study, the authors aim to evaluate clinical features and treatment results observed in patients from the German and Italian studies who had nonmetastatic abdominal rhabdomyosarcomas (RMS). METHODS: One hundred sixty-one patients were observed; 78 registered in the German studies between October 1980 and August 1995, and 83 registered in the Italian studies between April 1975 and December 1995. The age range of the patients was 0-18 years (median, 4 yrs). The distribution of tumor sites was as follows: 32 intraperitoneal, 42 retroperitoneal, 75 pelvic, and 12 not otherwise specified (NOS). Most patients had a large and invasive primary mass (26 T1b, 114 T2b). The breakdown in histology was as follows: 116 embryonal, 34 alveolar, and 11 other (leiomyomatous, pleomorphic, and NOS); all cases were staged according to the Intergroup Rhabdomyosarcoma Studies (IRS) system. Nine Group I patients were treated after surgery with chemotherapy (CT) (radiotherapy [RT] was delivered to treat alveolar RMS in the 1991 German and 1988 Italian studies); 19 Group II patients received CT + RT (40-44 Gy); 133 Group III patients underwent neoadjuvant CT +/- surgery and/or RT (54 Gy) + CT. Different CT regimens (based primarily on the administration of vincristine, dactinomycin, doxorubicin, and cyclophosphamide or ifosfamide) were adopted. RT was not recommended for patients age < 3 years. RESULTS: The 10-year overall survival (OS) and progression-free survival (PFS) were 47.2% and 43.9%, respectively. The OS was related significantly to the following variables: histology (alveolar, 29.4% vs. nonalveolar, 52.1% [P = 0.0156]), tumor size (> 5 cm, 42.1% vs. < 5 cm, 81% [P = 0.005]), age (< 10 yrs, 51.4% vs. >or= 10 yrs, 27.8% [P = 0.02]), complete surgery at diagnosis or after CT (+/-RT) (70.4% vs. 34.4% without it [P = 0.0015]). Most patients who achieved the delayed local control had responded well to neoadjuvant CT. CONCLUSIONS: Tumor size, histology, age, and initial or delayed achievement of local control were important prognostic factors. Most relapsed patients had unfavorable outcomes.