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Biomedical subjects

F Mattavelli

Publications and source records attributed to F Mattavelli.

At least 19 recordsLinked to original sources

Primary chemotherapy followed by anterior craniofacial resection and radiotherapy for paranasal cancer.

BACKGROUND: To study prospectively the activity of primary chemotherapy with cisplatin, fluorouracil and leucovorin (PFL) in patients with paranasal cancer receiving surgery and postoperative radiotherapy. PATIENTS AND METHODS: Forty-nine patients, previously untreated, with resectable paranasal carcinoma were enrolled. PFL (leucovorin 250 mg/m2/day for 5 days as a 120 h continuous infusion (c.i.), 5-fluorouracil 800 mg/m2/day from day 2 as a 96 h c.i. and cisplatin 100 mg/m2 day 2 q 3 weeks) was planned for five courses. RESULTS: Thirty-two patients (65%) completed three or more chemotherapy courses. Two deaths from thrombotic events were observed after the first cycle. Eight cardiac toxicities were recorded during chemotherapy causing treatment discontinuation. Objective response to PFL was observed in 21 patients [43%; 95% confidence interval (CI) 29% to 58%], including four complete responses (CRs) (8%; 95% CI 2% to 20%) and 17 partial responses (PRs) (35%). Pathological complete remission (pCR) was achieved in eight of 49 patients (16%). At 3 years, overall survival was 69% and event-free survival 57%. Overall and event-free survival in patients achieving pCR is 100%. CONCLUSIONS: PFL is active in paranasal cancer. Patients who attain a pathological complete remission have a favorable prognosis. Cardiovascular complications represent the limiting toxicity. Primary chemotherapy combined with surgery-sparing treatment approaches deserves further investigation.

Adult↗

[Lymph node metastases in paranasal sinus carcinoma: prognostic value and treatment].

The purpose of this report is to assess, on the basis of a sizeable study, the prognostic value of lymph node metastases in paranasal sinus carcinoma and, in particular, in squamous cell carcinoma of the maxillary sinus. We have reviewed the charts of 601 cases of paranasal sinus carcinoma between 1970 and 1999. All of the patients were treated surgically, alone or associated with chemotherapy and/or radiotherapy. The maxillary sinus tumors numbered 379 (153 squamous cell carcinomas, 15 undifferentiated carcinomas, 94 adenoid cystic carcinomas, 19 adenocarcinomas, 98 mesenchymal tumors and rare forms) and the ethmoidal tumors were 222 (117 adenocarcinomas, 27 squamous cell carcinomas, 16 adenoid cystic carcinomas, 13 undifferentiated carcinomas, 49 other histological forms). Lymph node metastases in ethmoidal tumors were rare, with the exception of undifferentiated carcinoma (46.1%). The percentages of metastatic squamous cell carcinoma of the maxillary sinus upon presentation were: T2 15.5%, T3 7%, and T4 4%. All these patients underwent lymph node excision. The metastases successive to treatment of the primary tumor were: T2 16.9%, T3 8.8%, and T4 12%. 75% of these late metastases occurred contemporaneously with a recurrence of T and only 5 (25%) constituted the single reawakening of disease; four of these patients underwent neck surgery and were cured operatively. One had fixed, inoperable metastases. The NED survival rate at least two years after T therapy in patients free from metastases was 50.4%, against 25% in those with initial or distant metastases (T2 72.9% vs. 30.4%, T3 37.5% vs. 22.2%, and T4 28.6% vs. 0%). In conclusion, squamous cell carcinomas of the maxillary sinus which have extended to the oral cavity (T2) show greater lymph node propagation than those of the superoposterior portion (T3-T4). The presence or successive appearance of lymph node metastases indicates elevated malignancy of the tumor, with a very negative prognosis. N, however, is rarely the cause of death for these patients. Prophylactic lymph node excision in N0 patients is therefore not indicated.

Antineoplastic Agents↗

Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): Phase I study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of clinical activity.

BACKGROUND: This study was designed to determine the feasibility, maximum tolerated dose, and toxicities of intraarterial administration of paclitaxel-albumin nanoparticles in patients with advanced head and neck and recurrent anal canal squamous cell carcinoma. Antitumor activity also was assessed. METHODS: Forty-three patients (31 with advanced head and neck and 12 with recurrent anal canal squamous cell carcinoma) were treated intraarterially with ABI-007 every 4 weeks for 3 cycles. In total, 120 treatment cycles were completed, 86 in patients with head and neck carcinoma (median, 3 cycles; range, 1-4) and 34 in patients with anal canal carcinoma (median, 3 cycles; range, 1-4). ABI-007 was compared preliminarily with Taxol for in vitro cytostatic activity. Increasing dose levels from 120 to 300 mg/m2 were studied in 18 patients. Pharmacokinetic profiles after intraarterial administration were obtained in a restricted number of patients. RESULTS: The dose-limiting toxicity of ABI-007 was myelosuppression consisting of Grade 4 neutropenia in 3 patients. Nonhematologic toxicities included total alopecia (30 patients), gastrointestinal toxicity (3 patients, Grade 2), skin toxicity (5 patients, Grade 2), neurologic toxicity (4 patients, Grade 2) ocular toxicity (1 patient, Grade 2), flu-like syndrome (7 patients, Grade 2; 1 patient, Grade 3). In total, 120 transfemoral, percutaneous catheterization procedure-related complications occurred only during catheterization of the neck vessels in 3 patients (2 TIA, 1 hemiparesis) and resolved spontaneously. CONCLUSIONS: Intraarterial administration of ABI-007 by percutaneous catheterization does not require premedication, is easy and reproducible, and has acceptable toxicity. The maximum tolerated dose in a single administration was 270 mg/m2. Most dose levels showed considerable antitumor activity (42 assessable patients with 80.9% complete response and partial response). The recommended Phase II dose is 230 mg/m2 every 3 weeks.

Adult↗

[Malignant maxillary tumors involving the pterygo-maxillary and infratemporal fossae: a series of 200 cases].

At the Cranio-Maxillo-Facial Surgery Unit of the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan, Italy between 1987 and 1999 200 anterior cranio-facial resections were performed on malignant ethmoid tumors involving the anterior cranial base and extending to the nasal fossae and, at times to the orbit and maxillary and sphenoid sinuses. In the second portion of this case study the authors simplified their surgical technique. The frontal craniotomy was made rectangular and low, performed with an oscillating saw and scalpel, without drilling holes. The osteotomy of the cranial base was modulated according to tumor extension. Typically a paralateronasal facial incision was performed without opening the upper lip. Whenever the maxillary sinus and/or orbit were involved, the skin incision and osteotomy was consequently modified. Repair of the cranial base was performed with a pedicled pericranial flap. In this case study there were 6 post-operative deaths in the first 30 patients and only 2 in the remaining 170. The male/female ratio was 145/55, mean age 55 years (12-80) and average follow-up 38 months (2-117). There were 120 primary tumors while the remaining 80 patients presented recurrences from prior treatments. There were 96 adenocarcinomas, 42 spinocellular carcinomas, 21 esthesioneuroblastoma 15 adenoid-cystic carcinomas, 9 melanomas and 17 rare tumors. Our classification identified the following stages: 69 T2, 54 T3 and 77 T4 while the UICC-AJCC staging system indicated: 25 T1, 16 T2, 68 T3 and 91 T4. The NED survival according to tumor stage (INT classification) was: T262.3%, T3 44.4% and T4 29.9%. The NED survival for patients who had not previously undergone treatment was: T2 71.7%, T3 58.8% and T4 42.5%. On the other hand the NED survival for the cases of recurrence was: T2 43.5%, T3 20% and T4 16.2%. These results lead to the conclusion that the surgical technique currently used is valid and that the anterior cranio-facial resection should always be performed in patients with ethmoid tumors coming into contact with, or eroding, the cribriform plate. For all staging classes, the prognosis for those patients undergoing surgery for recurrence from prior, inadequate treatment was significantly worse than that for the primary tumors.

Adolescent↗

[Malignant maxillary tumors involving the pterygo-maxillary and infratemporal fossae: a series of 65 patients and a comparison of the 1997 and 1977 UICC-AJCC staging systems].

The prognosis for maxillary malignancies with posterior extension to the pterygo-maxillary and infratemporal fossae is worse than for those with anterior-inferior extrinsication. Maxillectomy using only an anterior approach does not enable enblock, radical resection of such tumors. Many different approaches to the infratemporal fossae have been described in the literature. The authors use a double infratemporal and transfacial approach. Between 1990 and 1998 this approach was used on 65 patients with malignant maxillary tumors. There was one post-operative death due to myocardial infarction. There were only 9 cases of temporal infection, and all were resolved. There were no cases of necrosis of either the temporal muscle or the revascularized flaps. The cases included the following tumors: spinocellular and anaplastic carcinoma (21 cases); adenoid-cystic carcinoma (16); adenocarcinoma (4); sarcoma (18); other malignant tumors (6). There were 29 primary tumors while the remaining 36 were recurrences from prior treatment. Using the UICC-AICC 1987-92 staging system there were 22 cases of T3 and 43 T4. Using the 1997 system there were 35 T3s and 30 T4s. Resection was radical in 54 cases while in the remaining 11 there were micro or macroscopic limitations at the rhinopharyngeal level and/or at the orbit apex. The NED survival percentages were: T3 59.2%; T4 28% (using the 1987-92 system) while they were T3 45.7% and T4 26.7% (using the 1997 system). In the 41 patients with carcinoma (spinocellular, anaplastic, adeno and adenoid-cystic) the NED survival percentages were: T3 54.5%; T4 23.4% (using the 1987-92 system) while they were T3 45% and T4 19% (using the 1997 system). The NED survival percentage was 41.4% for primary tumors and 36.1% for recurrences. These results lead one to conclude that this surgical technique permits good results with T3-T4 maxillary malignancies. The prognosis for recurrences is worse than for primary tumors and the prognosis for sarcoma is better than for carcinoma. The UICC-AICC staging systems are valid for prognostic purposes. The current analyses indicate that the 1987-92 system is slightly more suitable than the 1997 system. In fact, there were 13 patients which the 1987-92 system had classified as T4 and which the 1997 system had reclassified as T3. In all these cases the prognosis was more similar to that of T4 than T3.

Adolescent↗

Combined anterior craniofacial resection for tumors involving the cribriform plate: early postoperative complications and technical considerations.

OBJECTIVE: Combined craniofacial resection has become the standard approach for malignant tumors involving the cribriform plate and anterior cranial fossa. Despite its widespread application, however, many surgeons agree that the procedure carries a risk of significant morbidity and even mortality. The purpose of this study was to analyze the experience at a single institution to determine the incidence of early postoperative complications encountered after combined craniofacial resection of tumors involving the cribriform plate and to provide information to improve management. METHODS: Between 1987 and 1997, 168 patients underwent combined craniofacial resection at the National Cancer Institute of Milan for tumors involving the cribriform plate. Patient charts, operative notes, follow-up clinic notes, radiographic studies, and pathology reports were analyzed. Morbidity encountered in the first 30 cases was compared with that encountered in the subsequent 138 cases. RESULTS: The most frequently encountered pathological findings were adenocarcinoma (53.6%), squamous cell carcinoma (17%), and esthesioneuroblastoma (9.8%). Eight patients (4.7%) died, 6 of whom were among the first 30 patients to undergo resection. Among patients with fatal complications were three with meningoencephalitis, three with intracranial hemorrhage, and one with myocardial infarction. Fifty patients (29.7%) had nonfatal morbidity; 16 of these patients were among the first 30 patients operated. Transient cerebrospinal fluid leakage was the most frequent adverse effect (9.5%); 12 patients (7.1%) had pneumocephalus, 3 (1.8%) had meningitis, 4 (2.4%) had wound infections, 3 (1.8%) experienced transient impairment of mental status, 3 (1.8%) had transient diplopia, 2 (1.2%) had diabetes insipidus, and 1 (0.6%) had bone flap necrosis. CONCLUSION: We observed a dramatic decrease in mortality and morbidity in patients who underwent combined craniofacial resection after the first 30 cases in our series. Improvement of specific aspects of surgical technique, such as more refined reconstructive methods and improved prophylactic antibiotic therapy, is at least partly responsible for this favorable trend.

Adult↗

A new classification for malignant tumors involving the anterior skull base.

OBJECTIVES: To propose our clinical classification of malignant ethmoid tumors and to compare it with the last American Joint Committee on Cancer (AJCC)-Union Internationale Contre le Cancer (UICC) classification, published in 1997. DESIGN: Retrospective review. SETTING: Tertiary cancer facility. PATIENTS: We evaluated 123 consecutive patients undergoing craniofacial resection for malignant ethmoid tumors involving the anterior skull base. The mean follow-up was 60 months. Fifty-nine patients (48%) presented with recurrent disease after prior therapy. We classified them with a new classification system (Istituto Nazionale per lo Studio e la Cura dei Tumori) based on the most commonly accepted unfavorable prognostic factors (involvement of dura mater; intradural extension; involvement of the orbit and, in particular, of its apex; invasion of maxillary, frontal, and/or sphenoid sinuses; and invasion of the infratemporal fossa and skin. We also classified patients with the AJCC classification published in 1997. MAIN OUTCOME MEASURES: Disease-free status and overall survival rate. To study a possible association with tumor stage, the Cox regression model was adopted. RESULTS: According to our classification, patient distribution by tumor type was T2, n = 46; T3, n = 29; and T4, n = 48 (no T1 tumors were present in the series). For previously untreated patients, 5-year disease-free survival estimates were T2, 57%; T3, 50%; and T4, 13%. For relapses, corresponding figures were T2, 31%; T3, 23%; and T4, 1%. The prognostic difference among stages was statistically significant (P<.001). Similar results were obtained for overall survival. In contrast, patient distribution among different AJCC stages was less balanced, and we failed to detect a significant association with the clinical outcome using this classification. CONCLUSION: We propose the use of our staging system by all those specialists in the field willing to validate the classification and possibly apply it for clinical and investigational purposes.

Adult↗

Anterior craniofacial resection for malignant ethmoid tumors--a series of 91 patients.

BACKGROUND: Anterior craniofacial resection is now recognized as the best treatment for ethmoid tumors involving the cribriform plate with or without invasion of anterior cranial fossa. METHODS: Ninety-one patients underwent an anterior craniofacial resection for ethmoid malignant tumors at the Milan Cancer Institute between 1987 and 1994. The patient population was divided into two sections (30 and 61 patients) based upon some important variants (type of craniotomy, antibiotic treatment, postoperative care). RESULTS: The mean age was 53.4 years (range, 24 to 78 years). There were 62 men and 29 women. Forty-nine patients had a recurrence after previous treatments (surgery and/or radiotherapy). The subdivision by histology was as follows: 50 cases of adenocarcinoma, 16 cases of epidermoid and undifferentiated carcinoma, 8 cases of esthesioneuroblastoma, 5 cases of adenoid cystic carcinoma, 5 cases of melanoma, and 6 rare tumors. The stages (according to our new staging) were as follows: 37 cases with T2, 27 cases with T3, and 27 cases with T4. The mean follow-up was 47 months. Seven patients died after surgery (6 in the first series). The survival at 3 and 5 years was, respectively, 52% and 47%, and the disease-free survival (DFS) was 30% and 24%, with a statistically significant difference at multivariate analysis in favor of patients without prior treatment (p = .033) or T2 versus T3 and T4 (p<.007). CONCLUSIONS: An anterior craniofacial resection should be performed in cases of ethmoid tumors reaching or eroding the cribriform plate. A scrupulous intra- and postoperative approach is necessary to avoid severe complications. The patients often survive for a long time with recurrence ongoing. Our new staging identifies the critical extensions of ethmoid tumors.

Adenocarcinoma↗

Skull base reconstruction after anterior craniofacial resection.

Anterior craniofacial resection has become a popular operation for nasoethmoid tumours involving the skull base. Many papers have been published since the first by Ketcham et al. in 1963. However, there is still controversy about the method for reconstruction of an anterior skull base defect after resection. The simple reconstruction of Ketcham has been followed by more sophisticated procedures using galeal-pericranial flaps, free flaps with microvascular anastomosis and bony or alloplastic augmentation. The main purposes of the reconstructions are to prevent brain herniation, to avoid intracranial infections, to diminish the risk of CSF leakage and to avoid pneumocephalus. From the relevant literature and our own experience of 168 anterior craniofacial resections, we conclude that a pedicled pericranial flap is the best choice for closing a cranial base defect.

Cerebrospinal Fluid↗

[Classification of ethmoid malignancies].

The UICC and AJCC never classified ethmoid malignancies prior to the latest edition (1997). Most classifications in the literature refer to a single histological type (estensioneuroblastoma or carcinoma) while others basically consider the intracranial extension, without distinguishing between intra or extradural. Still others consider invasion of the orbit. There is as yet no classification which considers all the prognostic factors associated with the extension of this neoplasm. The authors reviewed 84 patients with ethmoid malignancy who had undergone anterior cranio-facial resection between 1987 and 1994 and had been followed up for a minimum of 36 months. Of these patients, 43 were recurrences of previous treatment while 42 had not previously been treated. The breakdown was as follows: 45 adenocarcinoma, 14 squamous cell carcinoma (more or less differentiated), 8 etesioneuroblastoma, 6 adenoidocistic carcinoma, 5 melanoma and 6 rare forms. These cases were staged according to a new classification identifying the worst prognostic factors: invasion into the dura and, above all, intradural extension; invasion of the sphenoid sinus, orbit, and in particular the orbit apex, the frontal sinus, the maxillary sinus, the pterygoid, infratemporal fossa and the skin. Until 1994 we used this classification which is similar to the one proposed by the UICC in 1997. On the basis of this classification our case breakdown is as follows: T2 35, T3 24, T4 25 (there were no cases of T1). Since a patient can live as much as 4-5 years with a recurrence but the recurrences all appeared within 2 years after surgery, we used a NED survival at 36 months as index of healing. The NED survival at 36 months was: T2 54%, T3 41%, T4 8%. In patients which had not received prior treatment the NED survival was: T2 63%, T3 45%, T4 9%. The progressive worsening of prognosis from T2 to T4, particularly in patients which had not been pretreated, leads us to assume that the true prognostic factors for malignant ethmoid tumors have been identified.

Ethmoid Sinus↗

[Combined transfacial and infratemporal approaches for T3-T4 malignant maxillary tumors].

The technique of maxillectomy employing an anterior transfacial approach has practically remained unaltered since historical and suggestive descriptions of Lizars reported in 1829 and those of Fergusson reported in 1842. This procedure is suitable and efficacious for benign tumors as well as for malignant tumors which involve the inferior, anterior, medial or lateral wall of the maxillary sinus. However, when the tumor erodes the posterior wall, surrounding and destroying the pterygoid and invading the pterygo-maxillary and the infratemporal fossae, sometimes causing thrismus as a result of infiltration of the pterygoid muscles, surgical control of the posterior extension through an anterior approach is impossible. Many authors maintain that in these cases surgery is useless if not detrimental in light of the low survival rates reported. We propose a new surgical technique (a double approach--transfacial and infratemporal preauricolar) to be followed in these patients. These approaches allow us to completely surround the extension of the tumor as well as to achieve surgical radicality in T4. Moreover, with this technique it is possible to use the temporalis muscle to repair the resulting post-maxillectomy cavity thus eliminating the necessity of the obturator. From 1992 to 1994 we operated 46 patients with T3 and T4 malignant tumors of the maxillary sinus following this procedure. We had 1 death due to heart infarction 3 days after surgery. On the other hand no serious local complications were observed. There were only 7 suppurations in the temporal region, either resolved quickly and spontaneously or through simple surgical drainage. The follow-up is still too brief to allow us to draw definite conclusions. At any rate, presently 30 of our 46 patients are alive and disease free.

Adolescent↗

Cell kinetics and response to primary intra-arterial chemotherapy in patients with advanced oral cavity tumors.

The relationship was analyzed between cell kinetics, defined as 3H-thymidine labeling index (3H-TdR LI), and clinical responses for 35 previously untreated patients with locally advanced oral cavity squamous cell carcinomas. Patients were treated with three cycles of vincristine and bleomycin (VB) or of VB plus methotrexate (VBM), given by intra-arterial infusion followed by surgery. The objective clinical response rate was higher after VBM treatment than after VB, whereas overall clinical response rates were similar for patients with slowly or rapidly proliferating tumors. The probability of relapse-free survival at 4 yr and overall survival was significantly higher for patients with high 3H-TdR LI tumors given VBM than for those given VB. For patients with slowly proliferating tumors, there were no differences in relapse-free survival and overall survival between the two treatments. These data suggest that patients with rapidly proliferating tumors benefit from primary intensive chemotherapy treatment including methotrexate and that cell kinetics can be used to formulate rational clinical protocols for oral cavity cancers.

Adult↗

Iatrogenic pneumocephalus in a man with undifferentiated nasopharyngeal carcinoma. A case report.

A case of pneumocephalus in a 45-year-old male with undifferentiated rhinopharyngeal carcinoma is described. The patient was initially subjected to radiotherapy and then to transmaxillary resection and a second course of stereotactic radiotherapy for recurrent disease. Lastly, the patient was treated with chemotherapy because of local-regional disease progression. After two cycles of cisplatin, adriablastine and bleomycin, the patient suddenly entered in coma. Cerebral CT scan evidenced the presence of air in the frontal and lateral cornua, in the subarachnoid space of the base cisternae extending to the 7th cervical vertebra. After 8 months of a clinical stationary condition, the patient died. The various treatments used are critically reviewed, and modern therapeutic approaches for the neoplasm and the toxicity involved are discussed. We conclude that in nasopharyngeal carcinoma, for patients who relapse after radiotherapy, successive local-regional therapies (surgery, re-irradiation) should be carefully evaluated to avoid demolishing treatments, which are burdened with severe side effects that might influence the quality of life with only slight improvement of overall survival. Furthermore, the presence of persistant aqueous rhinorrhea in these patients should be carefully evaluated, because it could be an early symptom of a cerebrospinal fluid leak.

Carcinoma↗