Enhanced polyhydroxyalkanoate (PHA) production from the organic fraction of municipal solid waste by using mixed microbial culture.

BACKGROUND: In Europe, almost 87.6 million tonnes of food waste are produced. Despite the high biological value of food waste, traditional management solutions do not consider it as a precious resource. Many studies have reported the use of food waste for the production of high added value molecules. Polyhydroxyalkanoates (PHAs) represent a class of interesting bio-polyesters accumulated by different bacterial cells, and has been proposed for production from the organic fraction of municipal solid waste (OFMSW). Nevertheless, until now, no attention has been paid to the entire biological process leading to the transformation of food waste to organic acids (OA) and then to PHA, getting high PHA yield per food waste unit. In particular, the acid-generating process needs to be optimized, maximizing OA production from OFMSW. To do so, a pilot-scale Anaerobic Percolation Biocell Reactor (100 L in volume) was used to produce an OA-rich percolate from OFMSW which was used subsequently to produce PHA. RESULTS: The optimized acidogenic process resulted in an OA production of 151 g kg-1 from fresh OFMSW. The subsequent optimization of PHA production from OA gave a PHA production, on average, of 223 ± 28 g kg-1 total OA fed. Total mass balance indicated, for the best case studied, a PHA production per OFMSW weight unit of 33.22 ± 4.2 g kg-1 from fresh OFMSW, corresponding to 114.4 ± 14.5 g kg-1 of total solids from OFMSW. PHA composition revealed a hydroxybutyrate/hydroxyvalerate (%) ratio of 53/47 and Mw of 8∙105 kDa with a low polydispersity index, i.e. 1.4. CONCLUSIONS: This work showed how by optimizing acidic fermentation it could be possible to get a large amount of OA from OFMSW to be then transformed into PHA. This step is important as it greatly affects the total final PHA yield. Data obtained in this work can be useful as the starting point for considering the economic feasibility of PHA production from OFMSW by using mixed culture.

Symptom interval in pediatric patients with solid tumors: adolescents are at greater risk of late diagnosis.

BACKGROUND: The awareness that adolescents can have cancer is probably insufficient, not only among teenagers and their families, but also among physicians, and adolescent patients are reportedly often referred to qualified cancer institutes after a considerable delay. PROCEDURE: A prospective series of 425 patients (28% of them adolescents) with solid tumors was analyzed to investigate the correlation between symptom interval and age, and the different contributions to symptom interval in terms of the time from symptom onset to the first contact with a doctor (patient delay), referral to the oncologist (referral delay), and final diagnosis (oncologist delay). RESULTS: The median symptom interval was 47 days for 0 to 14-year-old patients and 137 for those ≥15 years (P < 0.001). The greatest delay in the adolescent group related to the patient delay (63.3% of the total symptom interval). CONCLUSION: Adolescents are often diagnosed with longer delay as compared to children. The main contribution to symptom interval in adolescents appears to be due to the time they first go to a doctor; however, also the time taken by the physician to the patient to a specialist (oncologist or surgeon) able to define the diagnosis of cancer was longer for adolescents than for younger patients.

A prospective protocol for nasopharyngeal carcinoma in children and adolescents: the Italian Rare Tumors in Pediatric Age (TREP) project.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is very rare in childhood. It differs from its adult counterpart in the prevalence of the nonkeratinizing, undifferentiated subtype and by an advanced clinical stage at onset and better chances of survival. The risk of long-term treatment-related toxicity also may be a more important issue in younger individuals. METHODS: A prospective chemoradiotherapy protocol for pediatric NPC was started in Italy in 2000 within the framework of the Rare Tumors in Pediatric Age (TREP) project. Three courses of cisplatin/5-fluorouracil induction chemotherapy were followed by radiotherapy (doses up to 65 grays) with concomitant cisplatin. RESULTS: Forty-six patients (ages 9-17 years) were considered eligible for the study over a 10-year period. The ratio of observed to expected cases based on epidemiological data was approximately 1 for both children and adolescents. All but 1 patient had lymph node involvement, and 5 patients had distant metastases. The rate of response to primary chemotherapy was 90%. The 5-year overall and progression-free survival rates were 80.9% and 79.3%, respectively (median follow-up, 62 months). The only statistically significant prognostic variable was the presence or absence of distant metastases. A 65% incidence of late sequelae was reported. CONCLUSIONS: This study demonstrates the feasibility and efficacy of a prospective protocol even for such rare tumors as pediatric NPC. The use of lower radiotherapy doses than those used in adults did not affect locoregional failure rates. Long-term follow-up will be needed to obtain more information on both survival and treatment sequelae. The next objective will be to establish broader, international prospective cooperation schemes.

Prolonged 14-day continuous infusion of high-dose ifosfamide with an external portable pump: feasibility and efficacy in refractory pediatric sarcoma.

BACKGROUND: Ifosfamide is currently used to treat pediatric sarcomas and increasing its dosage may be associated with a better response rate. Prolonged continuous infusion seems an attractive administration modality. METHODS: Ifosfamide 14 g/m(2) (with mesna 14 g/m(2)) was administered through an ambulatory portable pump over 14 days as a continuous infusion, starting every 3 weeks, in 14 patients with relapsing sarcomas. No growth factors were given. RESULTS: Acute grade 3 hematological toxicity was observed in only 13/66 cycles and red cell transfusions were given in two patients. Hematuria and dysuria occurred in three cases. The response rate was: five partial responses, five stable disease. The median time to progression was 3 months (range: 2-19 months). The best response rate was seen for synovial sarcoma and Ewing sarcoma. CONCLUSION: Prolonged 14-day continuous infusion of high-dose ifosfamide is well tolerated. Potentially interesting preliminary responses in pediatric patients already treated with ifosfamide are reported.

Comparison of the prognostic value of assessing tumor diameter versus tumor volume at diagnosis or in response to initial chemotherapy in rhabdomyosarcoma.

PURPOSE: In this study on a series of 205 patients with rhabdomyosarcoma, we investigated whether the prognostic effect of tumor size, at diagnosis or in terms of tumor response after induction chemotherapy, differed when tumor diameter or tumor volume were considered. PATIENTS AND METHODS: Tumor size was assessed radiologically at diagnosis and, for the 108 patients with measurable disease, after three courses of chemotherapy. The analysis was based on multivariable models (linear for association between size and patient/tumor characteristics, Cox for association with survival). The predictive performance of the Cox model (estimated by V measure) was compared for the tumor's diameter and volume. RESULTS: Initial tumor size was significantly larger in male or older patients and in T2 or alveolar tumors, but was not associated with the achievement of complete surgical resection. Initial tumor size significantly influenced overall survival. The risk of death was comparable for tumors 10 cm in maximum diameter and 194.0 cm(3) in volume. The predictive performance of the Cox model was much the same when the tumor's diameter or volume was considered. Tumor response was a significant predictor of survival, again irrespective of the type of tumor measurement considered. CONCLUSION: In our analysis, initial tumor size and tumor response were significant prognostic factors in rhabdomyosarcoma, regardless of whether tumor diameter or volume was considered. Three-dimensional tumor assessment was of no greater prognostic value than one-dimensional assessment, neither initially nor after induction treatment.

The symptom interval in children and adolescents with soft tissue sarcomas.

BACKGROUND: In a series of 575 patients < or =21 years of age with soft tissue sarcomas (STSs), the authors investigated the association patterns between symptom interval (ie, the period between the onset of the first symptoms or signs of the disease and its definitive diagnosis) and patient/tumor characteristics or disease outcome (in terms of survival). METHODS: The analysis was based on multivariate models (linear for associations with patient/tumor characteristics and Cox's for survival). RESULTS: The symptom interval ranged between 1 week and 60 months (median, 2 months) and tended to be longer the older the patient (ie, the interval was longer in adolescents than in children) and the larger the tumor's size, and for tumors located at the extremities and for nonrhabdomyosarcoma STSs (as opposed to rhabdomyosarcomas). A longer symptom interval unfavorably influenced survival (P = .002), which was also significantly affected by the patient's age and the size and surgical stage of the tumor. A different pattern of association between symptom interval and survival emerged for different types of STS histology. CONCLUSIONS: Our study points to an independent prognostic effect of symptom interval that cannot be explained by its associations with other factors, such as patient's age or the site, size, stage, and histology of the tumor. Future studies should focus more on the possible causes of symptom interval in pediatric STS populations to enable corrective measures to be implemented to reduce the diagnostic delay.

Inflammatory myofibroblastic tumor of the conjunctiva: response to chemotherapy with low-dose methotrexate and vinorelbine.

Inflammatory myofibroblastic tumor (IMT) is an unusual entity that mainly affects children and young adults, and for which standardized therapies for inoperable cases are still lacking. We report on a 12-year-old patient with an extremely rare and inoperable conjunctival location that was treated with chemotherapy using low-dose methotrexate plus vinorelbine, achieving complete tumor remission. This regimen is usually well tolerated and may be considered as the treatment of choice for cases of unresectable advanced IMT.

Pancreatic tumors in children and adolescents: the Italian TREP project experience.

INTRODUCTION: Malignant pancreatic tumors are exceedingly rare in pediatric age and their clinical features and treatment usually go unappreciated by most pediatric oncologists and surgeons. METHODS: From January 2000 to July 2009, 21 patients <18 years old with pancreatic tumors were prospectively registered in the Italian cooperative TREP project dedicated to very rare pediatric tumors. RESULTS: Tumor types were 4 pancreatoblastomas, 2 pancreatic carcinomas, 3 neoplasms of the endocrine pancreas, and 12 solid pseudopapillary tumors. Three of the four patients with pancreatoblastoma had advanced disease at diagnosis and were given chemotherapy; at the time of this report, three patients were alive in first remission, while one died due to treatment toxicity. Both the cases of pancreatic carcinoma had the acinar cell subtype and successfully underwent pancreaticoduodenectomy with complete tumor resection, remaining without evidence of disease at the time of this analysis. The histological diagnoses of the three endocrine tumors were a malignant islet cell tumor, a gastrinoma, and a well-differentiated tumor. All 12 patients with solid pseudopapillary tumors underwent complete tumor resection and were given no adjuvant treatment; 11 were alive in first remission, while one experienced a local and distant relapse 5 years after diagnosis. CONCLUSIONS: Surgery remains the keystone of treatment for pancreatic tumors in pediatric age as in adults. The TREP project shows that prospective cooperative studies are feasible even for such very rare tumors as these and may serve as a model for developing international cooperative schemes.

Prognostic role of tumor size in childhood cancer.

Identifying prognostic factors that influence outcome is a key point in pediatric oncology, as it enables risk stratification and helps us to fine-tune risk-adapted treatments, thereby hopefully improving the chances of survival for high-risk patients, and minimizing the burden of treatment for those whose outlook is good. Along with other clinical and biological variables, tumor size at onset has been identified as a crucial variable in several pediatric malignancies, and in soft-tissue sarcomas in particular. This review provides a critical reappraisal of the prognostic role of tumor size in pediatric soft-tissue sarcomas.

Rhabdomyosarcoma of the extremities: a focus on tumors arising in the hand and foot.

BACKGROUND: Extremities are peculiar sites of origin for rhabdomyosarcomas (RMS) and are usually associated with an unfavorable outcome. METHODS: The authors reviewed the clinical data on 60 patients <21 years old with limb RMS treated at the Pediatric Oncology Unit of the Istituto Nazionale Tumori of Milan, in Italy, over a 30-year period. Twelve patients had tumors arising in the hand and foot. RESULTS: Complete tumor resection was achieved in 21 patients (but in only 1 case of hand/foot RMS); all patients received chemotherapy and 43 also had radiotherapy. The alveolar subtype was identified in 62% of cases. Half of the hand/foot cases had metastatic disease at onset. Overall survival at 5 years was 33% among the hand/foot cases and 56% for the others. Most of the relapsing cases had distant metastases. CONCLUSIONS: A particularly poor survival was observed for RMS of the hand/foot due its marked tendency to spread. Surgical resection is particularly difficult in such cases and a multimodality treatment approach seems crucial to improving their outcome.

An adolescent with rhabdomyosarcoma during pregnancy.

We report the case of a 15-year-old girl with a large gluteal and perineal rhabdomyosarcoma diagnosed at 24 weeks of pregnancy, whose management posed a great clinical dilemma for us. The patient refused to consider a therapeutic abortion, so we opted for a customized treatment with mild doses of chemotherapy administered weekly to control tumor growth while minimizing fetal and perinatal complications. After the delivery of a healthy female, we adopted a more intensive chemotherapy regimen plus irradiation. Despite an initially good response, the disease unfortunately progressed and the patient died of her disease.

Rectal burkitt lymphoma in childhood.

Lymphomas are the third most common cancer in children and Burkitt lymphoma (BL) accounts for about 40% of them. The rectum is extremely seldom involved in BL: 91 children were treated at our institution for BL between 1987 and June 2006, but none of them had involved the rectum. We report here on a 9-year-old boy who presented with bowel bleeding and subocclusion, which proved due to a BL of the rectum. The role of surgery for this tumor is limited nowadays, except for surgical emergencies, biopsies, and second-look surgery in selected cases.

Angiomatoid fibrous histiocytoma in an HIV-positive child.

Children with human immunodeficiency virus are at higher risk of developing tumor than the general population, non-Hodgkin lymphoma and Kaposi sarcoma being the most frequent malignant tumor in these patients. The report describes the case of a human immunodeficiency virus-seropositive girl who developed an angiomatoid fibrous histiocytoma of the soft part of the right knee.

Late relapse of embryonal rhabdomyosarcoma, botryoid variant, of the vagina.

We report on two very similar cases of vaginal embryonal RMS, botryoid variant, that relapsed 9 and 10 years after initial diagnosis, a few months after the menarche in both cases. A possible causal association with estrogen hormones is hypothesized, particularly for the second case described, in which estrogen receptors were negative in the primary tumor specimen and positive in the relapsing tumor specimen.