Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma.

BACKGROUND: To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with recurrent high-grade glioma (HGG) after failure of surgery, radiation therapy, and chemotherapy. PATIENTS AND METHODS: In this two-arm, open-label, phase II study patients were stratified according to their epidermal growth factor receptor (EGFR) gene amplification status. Cetuximab was administered intravenously at a dose of 400 mg/m(2) on week 1 followed by weekly dose of 250 mg/m(2). The primary end point for this study was the response rate in both study arms separately. RESULTS: Fifty-five eligible patients (28 with and 27 without EGFR amplification) tolerated cetuximab well. Three patients (5.5%) had a partial response and 16 patients (29.6%) had stable disease. The median time to progression was 1.9 months [95% confidence interval (CI) 1.6-2.2 months]. Whereas the progression-free survival (PFS) was <6 months in the majority (n = 50/55) of patients, five patients (9.2%) had a PFS on cetuximab of >9 months. Median overall survival was 5.0 months (95% CI 4.2-5.9 months). No significant correlation was found between response, survival and EGFR amplification. CONCLUSIONS: Cetuximab was well tolerated but had limited activity in this patient population with progressive HGG. A minority of patients may derive a more durable benefit but were not prospectively identified by EGFR gene copy number.

Cold snare endoscopic resection of nonpedunculated colorectal polyps larger than 10 mm. A retrospective series.

BACKGROUND AND AIMS: Cold snare polypectomy (CSP) is an accepted technique to remove diminutive or small (6-9 mm) polyps. Here we present a series of CSP for advanced non-pedunculated polyps (> 10 mm). PATIENTS AND METHODS: This is a retrospective, single operator study. A total of 111 patients with non-pedunculated polyps (Paris classification 0-IIa, 0-IIb, 0-Is) estimated > 10 mm, underwent CSP. RESULTS: A total of 129 polyps were removed (87 0-IIa, 18 0-IIb, 24 0-Is). The number of these polyps ranked according to size were as follows : 11-19 mm : 63 (49%), 20-29 mm : 44 (34%), > 30 mm : 22 (17%). Thirty-eight (29.5%) were sessile serrated adenomas, 47 (36%) were tubular adenomas, 25 (19.3%) were villous adenoma's and 18 (14%) were hyperplastic polyps. Forty-nine (38%) polyps were resected in a piecemeal fashion, submucosal injection with diluted Indigo Carmine was used in 24 (19%). Immediate oozing bleeding was frequent but in almost all patients rapid spontaneous haemostasis occurred. In only one patient haemostatic clipping was required (in order to achieve hemostasis). Preventive clipping was used in 3 patients. There were no complications. Seventy-two patients (with 87 lesions) had a follow-up colonoscopy. Of these 87 lesions, 9 had residual adenomatous tissue (10.3 %). According to the size of the original polyp, the distribution was as follows: 11-19 mm : 2/36 (5.5 %), 20-29 mm : 4/32 (12.5 %), > 30 mm : 3/19 (15.7%). CONCLUSION: CSP for advanced, non-pedunculated lesions is feasible, effective and extremely safe.

The Belgian Association for Study of the Liver Guidance Document on the Management of Adult and Paediatric Non-Alcoholic Fatty Liver Disease.

Non-Alcoholic Fatty Liver Disease (NAFLD) is highly prevalent and associated with considerable liver-related and non-liverrelated morbidity and mortality. There is, however, a lot of uncertainty on how to handle NAFLD in clinical practice. The current guidance document, compiled under the aegis of the Belgian Association for the Study of the Liver by a panel of experts in NAFLD, from a broad range of different specialties, covers many questions encountered in daily clinical practice regarding diagnosis, screening, therapy and follow-up in adult and paediatric patients. Guidance statements in this document are based on the available evidence whenever possible. In case of absence of evidence or inconsistency of the data, guidance statements were formulated based on consensus of the expert panel. This guidance document is intended as a help for clinicians (general practitioners and all involved specialties) to implement the most recent evidence and insights in the field of NAFLD within a Belgian perspective.

Comparison of L-758,298, a prodrug for the selective neurokinin-1 antagonist, L-754,030, with ondansetron for the prevention of cisplatin-induced emesis.

Substance P is localised in brainstem regions associated with emesis. Based on studies in the ferret, it was postulated that a neurokinin-1 (NK1) receptor antagonist would have antiemetic activity as monotherapy in humans receiving chemotherapy. L-758,298 is a water-soluble, intravenous (i.v.) prodrug for L-754,030, a potent and selective NK1 receptor antagonist. This double-blind, randomised, active-agent (ondansetron)-controlled study enrolled 53 cisplatin-naïve patients and evaluated the prevention of both acute (0-24 h) and delayed (days 2-7) emesis after cisplatin treatment (50-100 mg/m(2)). All patients received i.v. L-758,298 (60 or 100 mg) (n=30) or ondansetron (32 mg) (n=23) before cisplatin and efficacy was evaluated up to day 7 post-cisplatin. Nausea was assessed by means of a four-point ordinal scale at intervals over the 7 day period. In the acute period, the proportion of patients without emesis in the L-758,298 and ondansetron groups was 37 and 52%, respectively (no significant difference between the groups). Comparing the distribution of average nausea scores over the entire first 24 h revealed no significant difference between the groups. In the delayed period, the proportion of patients without emesis in the L-758,298 and ondansetron treatment groups was 72 and 30%, respectively (P=0.005). The distribution of average nausea scores in the delayed period was lower in the L-758,298 group compared with the ondansetron group (P=0.15 for the entire delayed period and P=0.043 for day 2 only). No serious adverse events were attributed to L-758,298. A single dose of L-758,298 substantially suppressed the delayed nausea and vomiting characteristic of high dose cisplatin and also appeared to reduce acute emesis post-cisplatin. The data also support the proposition that the underlying mechanism(s) of acute and delayed emesis are different.

Combination chemotherapy with carboplatin, cyclophosphamide and fluorouracil in advanced breast cancer.

Single agent carboplatin has demonstrated antitumoral activity in patients with advanced breast cancer. Thirty patients with inoperable locally advanced and/or metastatic breast cancer were treated with carboplatin (300 mg/m2) in combination with cyclophosphamide (600 mg/m2) and 5-fluorouracil (500 mg/m2) given on day 1 in a 4-weekly schedule. Of 29 patients evaluable for response, 4 presented CR and 4 PR (28%). Seven out of 19 chemotherapy-naive patients achieved CR (4) or PR (3) (37%). In contrast, only one patient out of 10 achieved PR in the group with previous adjuvant chemotherapy (10%). Responses were observed in primary tumours as well as in metastatic sites, including lymph nodes, lung, liver and skin. Median duration of response was 7.5+ and 3.8 months in CR and PR patients respectively. Toxicity was generally mild. Only 2 patients presented with clinically relevant hematologic toxicity. No significant non-hematologic toxicity was observed. It appears that this regimen, at the dosage and schedule studied, possesses only modest activity in patients with breast cancer, while being relatively atoxic. Carboplatin merits further investigation in this disease, but dosing should be individualised using e.g. a pharmacokinetic formula.

Stereotactic radiosurgery of vestibular schwannomas with a linear accelerator.

The authors describe their initial experience with stereotactic radiosurgery of 22 cases with vestibular schwannomas using a linear accelerator. 14 of them with a follow-up of at least one year were studied. 6-9 months after treatment 86% had central tumour necrosis, 71% tumour shrinkage and none of them evidence of tumour growth 3 patients developed reversible facial nerve impairment, 2 had permanent facial numbness. Hearing diminished in one case out of three with normal hearing and in two out of three with already diminished hearing. Although there is a general consensus that microsurgery is the treatment of choice for these benign tumours, stereotactic radiosurgery challenges this opinion. Stereotactic radiosurgery not only proves to be a valuable alternative for selected cases not suitable for microsurgery, but it is conceivable that it will become the treatment of choice for small vestibular tumours. Tumour control can be obtained in the majority of treated patients with fewer complications and with a higher rate of cranial nerve sparing. This series indicates that linear accelerators can achieve results similar to the Gamma Unit in the treatment of vestibular schwannomas.

Radiosurgery of cerebral arteriovenous malformations with a linear accelerator: preliminary report.

The authors present the results obtained in seven patients with arteriovenous malformations treated with radiosurgery on a linear accelerator. In four patients obliteration of the malformation was obtained after one year. Two of the patients had a transient period of acute brain oedema surrounding the radionecrotic nidus with neurological signs. The present position of radiosurgery in the treatment of arteriovenous malformations is discussed.

Stereotactic radiosurgery of cerebral metastases: preliminary results.

The authors have treated 11 solitary cerebral metastases in 9 patients with stereotactic radiosurgery. This relatively new technique of stereotactic single high dose radiotherapy (15-30 Gy to the 70% isodose) is explained. All metastases responded to treatment: six disappeared on CT scan, while the volume of the remaining five diminished significantly. All patients with neurological symptoms had a satisfactory recuperation. There were no complications inherent to the technique. The indications and advantages of this innovative form of "surgical" radiotherapy are discussed.

Cerebrospinal fluid oedema: a rare complication of the ventriculo-subgaleal shunt.

The ventriculo-subgaleal shunt is a useful technique for obtaining a temporary decompression of the ventricles in patients with obstructive hydrocephalus. A direct surgical approach to remove the obstruction can restore the CSF circulation. When the shunt tube is left behind after restoration of the CSF dynamics, an extensive CSF oedema can develop in the white matter along the drain, resulting in a severe clinical syndrome. A possible mechanism is discussed. Quick and adequate treatment proved that the cerebral damage is reversible.

The position of the patient during neurosurgical procedures on the posterior fossa.

Different parameters were measured on patients in six different positions during infratentorial surgery. One group of data served to prove that such patients were in a steady-state as far as their cardiovascular and ventilatory function was concerned. The other measured parameters concerned the intracranial pressure, the intracranial venous pressure and the cerebral perfusion pressure. It appeared from the comparison of these data, that the lateral sitting (45 degrees) position had important advantages and that in this position the possibility of unfavourable features (such as air-embolism) was minimized.

Postoperative epilepsy in subdural suppurations.

The incidence of postoperative epilepsy in patients who had brain abscesses or subdural empyema is studied in 78 cases. This study is an attempt to answer the question whether prophylactic anticonvulsant drugs influence the natural history of this type of epilepsy.

[Endometriosis of the terminal ileum--differential diagnosis of Crohn disease]. / Endometriose des terminalen Ileum--eine Differentialdiagnose des Morbus Crohn.

Ileocecal resection was performed in two female patients with stenosis of the terminal ileum. Histological findings confirmed the clinical diagnosis of Crohn's disease in the first case, although focal intestinal endometriosis was detected. The resection specimens of the other patient exclusively showed lesions of endometriosis extending from the subserosa to the mucosal tissue. Typical lesions of Crohn's disease were totally absent in this case. Although not very frequent, endometriosis is an important differential diagnosis of Crohn's disease in young females.