Sinonasal undifferentiated carcinoma: current trends in treatment

Sinonasal undifferentiated carcinoma (SNUC) is a rare and highly aggressive neoplasm of the paranasal sinuses, which has recently been characterized as a distinct pathologic entity. The prognosis for patients with SNUC is poor. Early case reports describe patients with lesions that were clinically advanced at initial presentation and surgically unresectable. Survival was reported in months after treatment with chemotherapy and radiation. As more experience was gained with treatment of SNUC, it was found that aggressive, combined surgical therapy of lesions previously considered unresectable has shown increased survival. We report a case of a 38-year-old man with SNUC originating in the posterior ethmoid, extending into the anterior cranial fossa and orbit, who was treated with preoperative hyperfractionated radiation therapy, chemotherapy, and craniofacial resection.     

Sinonasal hemangiopericytoma: case report and literature review

Hemangiopericytoma (HPC) is a rare vascular tumor that can arise in any organ system, but occurs most frequently in skeletal muscle. We present a case of a primary sphenoid sinus HPC unusual for its spontaneous remission after biopsy. There have been approximately 55 cases of sinonasal HPC reported in the literature, representing less than 5% of all lesions. In general, HPC behaves aggressively, demonstrating greater than 50% local recurrence and 10% metastatic disease. Although extended surgical resection is traditionally considered the most effective therapy for all HPC, critical literature review does not support this method of treatment for HPC occurring in the paranasal sinuses and skull base. Long-term follow-up indicates that the majority of sinonasal HPC have a benign clinical course regardless of treatment. As a result, we do not recommend extended resection as the initial therapy for sinonasal HPC. Instead, a period of observation coupled with serial MRI or CT scans should be used to detect tumor progression. These indolent tumors should undergo extended resection only after progression has been confirmed. In addition to the case report, a synopsis of the reviewed literature and a summary of treatment recommendations are also presented.     

Beneficial effects of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimetic, in zymosan-induced shock

1 The therapeutic efficacy of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a novel superoxide dismutase mimetic which scavenges peroxynitrite, was investigated in rats subjected to shock induced by peritoneal injection of zymosan. 2 Our data show that MnTBAP (given at 1, 3 and 10 mg kg-1 intraperitoneally, 1 and 6 h after zymosan injection) significantly reduce in dose dependent manner the development of peritonitis (peritoneal exudation, high nitrate/nitrite and peroxynitrite plasma levels, leukocyte infiltration and histological examination). 3 Furthermore, our data suggest that there is a reduction in the lung, small intestine and liver myeloperoxidase (MPO) activity and lipid peroxidation activity from MnTBAP-treated rats. 4 MnTBAP also reduced the appearance of nitrotyrosine immunoreactivity in the inflamed tissues. 5 Furthermore, a significant reduction of suppression of mitochondrial respiration, DNA strand breakage and reduction of cellular levels of NAD+ was observed in ex vivo macrophages harvested from the peritoneal cavity of zymosan-treated rat. 6 In vivo treatment with MnTBAP significantly reduced in a dose-dependent manner peroxynitrite formation and prevented the appearance of DNA damage, the decrease in mitochondrial respiration and the loss of cellular levels of NAD+. 7 In conclusion our results showed that MnTBAP was effective in preventing the development of zymosan-induced shock.     

Salvage therapy with ilosfamide and mitoxantrone in advanced ovarian cancer

OBJECTIVE:: To evaluate the anti-tumour activity and toxicity of ifosfamide(5 g/m² continuous infusion) and mitoxantrone (10 mg/ m² givenin combination every 3 weeks in patients with ovarian cancerresistant to at least two previous regimens which included platinum. PATIENTS AND METHODS:: Additional eligibility criteria were an ECOG performance status2 and measurable disease. Of 47 patients entered in the study,8 were defined as platinum-resistant and 39 as potentially sensitiveaccording to Markman's criteria. Thirty-five patients had alsoreceived pacitaxel as last treatment before entering this study.Tumour response was evaluated every three cycles. RESULTS:: One complete and 11 partial responses were reported, for anoverall response rate of 25% (95% CI: 14%–40%). Threeof the partial responders were resistant to num. None of the7 partial responders pretreated with had responded to it. Theoverall median urvival was months. Neutropema G4 was reportedin 18 patients(42%) with hospitalisation because of febrileneutropenia in 3 of them. CONCLUSIONS:: In patients with ovarian cancer failing least 2 previous therapiesincluding platinum, the nation of ifosfamide and mitoxantronehas shown antitumour activity comparable to that of paclitaxel,with accept able toxicity. Objective responses were reportedalso patients failing pacitaxel, suggesting a lack of crossresistance. ifosfamide, mitoxantrone, ovarian cancer     

Determination of vascularization of B-cell non-Hodgkin's lymphomas with four markers

We evaluated the microvessel area (an index of angiogenesis) by using the factor VIII-related antigen (factor VIII-RA), and the expression of three components of the subendothelial basement membrane, namely: tenascin, laminin and type IV collagen. The four markers were assessed by immunohistochemical methods in 57 B-cell non-Hodgkin's lymphomas (B-NHL) and 28 benign lymphadenopathies. We found that microvessel area and the basement membrane markers had a different distribution pattern in relation to the histological type and degree of malignancy. In reactive and atypical lymphoid hyperplasias and in follicular low- and intermediate-grade B-NHL, microvessels were distributed within the interfollicular zones. By contrast, diffuse intermediate-grade and high-grade B-NHL were highly vascularized and microvessels were closely related to the neoplastic cells. Microvessel area was significantly associated with tenascin expression in all histological grades. Conversely, it was not correlated to laminin and type IV collagen expression, especially in diffuse intermediate-grade and high-grade B-NHL, where the expression of these markers was poor and fragmented. Our study suggests that angiogenesis and tenascin expression are associated phenomena in B-NHL, and that both increase with the malignancy grade. The prognostic value of angiogenesis and tenascin in B-NHL warrants further assessment in follow-up studies.     

Propofol and thiopentone for caesarean section revisited: maternal effects and neonatal outcome

In 56 women undergoing elective caesarean section, general anaesthesia was induced with either propofol 1% or thiopentone 2.5% followed by 50% nitrous oxide in oxygen and isoflurane 0.75% until delivery. In the thiopentone group the arterial pressure rose following tracheal intubation and skin incision, while in the propofol group there was a significant tendency to hypotension immediately following induction of anaesthesia. There were differences in electroencephalogram (EEG) between the groups, while laryngoscopy, intubation and surgical stimulation had no effect on EEG pattern. Recovery after anaesthesia did not differ between groups. None of the patients had recall of the intraoperative period, but 53% of patients induced with propofol showed signs of light anaesthesia between induction and delivery. Neonates in the propofol group had lower Apgar scores 1 min after birth than those in the thiopentone group, but these differences were no longer significant at 5 min. No differences were noted in neurobehavioural status at 1, 4 and 24 h.     

Pharmacokinetics of VP16-213 given by different administration methods

Summary Plasma pharmacokinetics of VP16-213 were investigated after a 30–60 min infusion in 14 adult patients and six children. In adults the elimination half-life (T_1/2 ), plasma clearance (Cl_p) and volume of distribution (Vd) were respectively 7.05±0.67 h, 26.8±2.4 ml/min/m², and 15.7±1.8 l/m²; in children 3.37±0.5 h, 39.34±6.6 ml/min/m², and 9.97±3.7 l/m². After repeated daily doses no accumulation of VP16-213 was found in plasma. The unchanged drug found in the 24 h urine after administration amounted to 20–30% of the dose.In eight choriocarcinoma patients plasma levels of VP16-213 were measured after oral capsules and drinkable ampoules. The bioavailability compared to the i.v. route was variable, mean values being 57% for capsules and 91% for ampoules. In one further patient, with abnormal d-Xylose absorption results, VP16-213 was not detectable in plasma after the oral ampoule dose.Steady state levels investigated in three patients after 72 h continuous VP16-213 infusion (100 mg/m²/24 h) were around 2–5 g/ml. Levels of VP16-213 were undetectable in CSF after i.v. or oral administration.     

Conservative surgery for Stage I ovarian carcinoma in women of childbearing age

Objective To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas.
Design Retrospective study.
Participants Ninety-nine women aged 40 years or younger who underwent either primary surgery in our department or were referred after primary surgery performed elsewhere.
Methods Of the 99 women in our study, 56 underwent fertility-sparing surgery and 43 more radical surgery. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour.
Results Conservative treatment was conducted in 84% of nulliparous and in 33% of parous women; 62% of grade 1 tumours, 48% of grade 2, and 50% of grade 3 were treated conservatively. With a median follow up of seven years, we observed five recurrences (9%) of carcinoma in women treated conservatively and five (12%) in those treated more radically. Two women (one in each treatment arm) were saved after recurrence. Two recurrences after conservative surgery involved the residual ovary (3.6%). Two women developed borderline tumour in the contralateral ovary and both were treated by surgery.
Conclusion After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. The risk of recurrence in the contralateral ovary is low. Conservative surgery may be also considered in some Stage I grade 3 tumours and in some women with stage IC tumours.     

Glycolipids from sponges. Part 17. Clathrosides and isoclathrosides, unique glycolipids from the Caribbean sponge Agelas clathrodes

Two families of unique glycolipids, clathrosides A-C (2a-4a) and isoclathrosides A-C (5a-7a) were isolated from the Caribbean sponge Agelas clathrodes. Clathrosides and isoclathrosides are glycosides of a very-long-chain alcohol derived from fatty acids, a new class of glycolipids that appears to be characteristic of marine sponges. The six compounds differ in configuration and in the branching of alkyl chains. Stereostructures of the clathrosides were determined by NMR and CD spectroscopy, mass spectrometry, and chemical degradation. Location of the methyl branch on the proper alkyl chain required an exceptional 1-D TOCSY experiment, in which coherence was transferred through as many as 13 vicinal couplings.