Rapid superselective high-dose cisplatin infusion with concomitant radiotherapy for advanced head and neck cancer

PURPOSE: The purpose of this study was to evaluate the efficacy of rapid superselective high-dose cisplatin infusion with concomitant radiotherapy for previously untreated patients with advanced head and neck cancer. METHODS: Forty-three patients for whom surgery was contraindicated or who rejected radical surgery were given superselective intra-arterial infusions of cisplatin (100-120 mg/m2/week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and conventional extra-beam radiotherapy (65 Gy/26 f/6.5 weeks). RESULTS: Thirty-nine patients had stage IV disease, and the remaining four had stage III disease. During the median follow-up period of 21 months, the 3-year locoregional progression-free rates of all patients (n = 43) and patients with unresectable disease (n = 24) were 68.9% and 56.4%, respectively. In addition, the 3-year overall survival of all patients and patients with unresectable disease was 54.0% and 39.6%, respectively. Thirty-five patients (81.4%) experienced nonhematologic grade III to IV toxicity, including mucositis (n = 16), nausea/vomiting (n = 8), and neurologic signs (n = 2). No patient died as a result of treatment toxicity. There are 29 surviving patients without evidence of disease, all of whom are able to have oral intake without feeding-tube support. CONCLUSIONS: We confirmed the efficacy of superselective arterial infusion and concomitant radiotherapy, which can concentrate the attack of supradose cisplatin on locoregional disease. Even patients with unresectable disease can be cured. Further studies are needed to establish the indications, long-term outcome, and possible late side effects of this treatment.     

Combined training of GPs and practice-assistants on peripheral arterial disease: positive effects after six months

OBJECTIVES: To improve the use of the ankle-brachial index (ABI) measurement, and management of patients with peripheral arterial disease (PAD) a combined training, targeting GPs and practice assistants (PAs) was developed. To measure the effect of the combined training on the management of patients with PAD, a cross-sectional study was performed. METHODS: Fifty consecutive patients referred by GPs to a vascular surgery out-patient clinic were analysed. Six months after the training an additional fifty patients were included. In all patients the ABI measurement, risk factor management, and treatment as performed by the GP, prior to referral, were analysed. RESULTS: The measurement of the ABI significantly increased from 10% before the training to 53% after the training (GPs with training: 83%, GPs without training: 35%; P: 0.001). The referral of patients with actual PAD significantly increased from 32% before the training to 70% after the training (GPs with training: 83%, GPs without training: 59%; P: 0.05). The presence and treatment of risk factors did not differ between the groups. CONCLUSIONS: Within the limitations of a before and after study the combined training of GPs and PAs appears to be an effective method to increase ABI measurements and significantly improve adequate diagnostics.     

Clinical evaluation of the Sorin Synthesis oxygenator with integrated arterial filter

The use of arterial line filters has long been a standard of practice in the field of cardiopulmonary bypass. Sorin Biomedica has designed an adult hollow-fiber oxygenator that not only incorporates their Mimesys biomimicry coating technology but also has a 40-micron arterial filter as an integrated component of this unique membrane oxygenator. We did a prospective, randomized clinical trial of 54 Synthesis coated oxygenators and compared them with 54 uncoated Monolyth Pro oxygenators, the latter of which incorporated an external arterial line filter with a standard bypass loop There were few statistically significant differences found between the Synthesis group and the Monolyth group with regard to pressure differentials, hemodynamic resistance, and platelet drop. The Synthesis oxygenator did require less priming volume, but the amount was not significant. Platelet counts with the Phosphorylcholine coated Synthesis oxygenators, using crystalloid perfusates, was similar to our previously published data on platelet protection and Albumin perfusates. We conclude that the Sorin Synthesis oxygenator appears to have better flow characteristics than the Monolyth oxygenator, with the potential for lower priming volumes. The most clinically significant benefit comes from the elimination of the arterial filter bypass loop and the avoidance of inverting the arterial filter during priming.     

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver

AIM: In nonresectable cholangiocellular carcinoma (CCC) therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%. Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver. METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m2) and additional transarterial chemoembolization procedures (50 mg/m2 cisplatin, 50 mg/m2 doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity. RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO Ⅲ/Ⅳ) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered. Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases, stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo. CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.     

Pulmonary arterial hypertension: the key role of echocardiography

Given the nonspecific nature of its early symptoms and signs, pulmonary arterial hypertension (PAH) is often diagnosed in its advanced stages. Although clinical assessment is essential when initially evaluating patients with suspected PAH, echocardiography is a key screening tool in the diagnostic algorithm. It not only provides an estimate of pulmonary pressure at rest and during exercise, but it may also help to exclude any secondary causes of pulmonary hypertension, predict the prognosis, monitor the efficacy of specific therapeutic interventions, and detect the preclinical stage of the disease.     

Effects of recombinant-hemoglobin solutions rHb2.0 and rHb1.1 on blood pressure, intestinal blood flow, and gut oxygenation in a rat model of hemorrhagic shock

The vasoconstriction induced by hemoglobin-based oxygen carriers (HBOCs), mainly a result of nitric oxide (NO) scavenging, until now has limited the application of HBOCs as resuscitation fluids. In this study, we tested the hypothesis that the new modified recombinant-hemoglobin solution rHb2.0, with a 20 to 30 times lesser NO-scavenging rate, would minimize vasoconstriction without adverse effects on microvascular oxygenation. Responses were compared with those to rHb1.1, a recombinant-hemoglobin solution with a wild-type NO-scavenging rate, as well as an oncotically matched albumin solution. In a fixed-pressure (40 mm Hg) rat model of hemorrhagic shock and resuscitation, rHb2.0 and albumin both restored mean arterial pressure (MAP) to baseline values, whereas rHb1.1 increased MAP to 27% above the baseline value. Mesenteric vascular resistance after resuscitation with rHb2.0 was 57% less than that with rHb1.1. rHb2.0 was found to have 55% greater intestinal oxygen delivery (Do2int ) and resulted in a 27% lower oxygen-extraction rate than did rHb1.1 after resuscitation. Intestinal microvascular Po2 , determined on the basis of oxygen-dependent quenching of palladium-porphyrin phosphorescence, revealed no difference between rHb2.0 and rHb1.1. The findings of this study confirm that the well-known pressure effect of HBOCs is caused by their effect on the NO-scavenging rate; recombinant modification of this rate did not increase MAP during resuscitation compared with baseline values. Although systemic vasoconstriction was absent, intestinal vasoconstriction almost negligible, and Do2int greater after resuscitation with rHb2.0, the effect of rHb2.0 on pH, base-excess and microvascular Po2 levels after resuscitation were comparable to those achieved with the use of the albumin solution.     

Percutaneous entry of the brachial artery for left heart catheterization using a sheath

Percutaneous entry of the brachial artery using a sheath system has been attempted in 223 patients undergoing left heart Catheterization; successfully, In 212. After arterial puncture, a dilator and sheath are passed over a short guWewire. A number 7–80 cm Sones specially stiffened coronary catheter Is passed through the sheath, and left heart Catheterization Is performed in the usual manner. The study can usually be completed with this single catheter. Initial entry, as well as any needed catheter change, Is facilitated by the use of an inflatable sphygmomanometer cuff around the upper arm. Ease of manipulation and patient comfort have been satisfactory, and brachial artery spasm has not been encountered. There have been no major complications and a low incidence (～ 1.5%) of brachial arterial occlusion.     

Systemic-pulmonary arteriovenous fistula of traumatic origin: A case report

Arteriovenous fistulas between the systemic circulation and the pulmonary artery are extremely rare. Continuous precordial murmur is the usual clinical sign while unilateral rib notching may be the only radiologic manifestation of this condition. Selective angiographic investigation is necessary to localize the site of such an arteriovenous (AV) fistula before surgery is performed. In a review of the literature of 15 published cases, the majority were of congenital origin, with four of these systemic-pulmonary AV fistulas of traumatic origin, of which one occurred after insertion of an intercostal catheter. We describe one case of traumatic origin 9 years after percutaneous thoracic drainage for spontaneous pneumothorax, in which transcatheter embolic occlusion of the feeding arteries of an AV fistula was attempted. The advantages and the disadvantages of the nonsurgical and surgical therapeutic approaches are discussed.     

RENAL, ADRENAL AND VASCULAR CHANGES DURING INHIBITION OF CONVERTING ENZYME WITH CAPTOPRIL

1. In rats treated continuously with captopril (80 μg/h, i.p.), for 2 days, blood pressure decreased and adrenal angiotensin II receptor concentration was decreased from 160 fmol/mg protein (s.e.m.=9) in controls to 131 fmol/mg protein (s.e.m. = 7, P < 0.01, n= 10). However, after 5 days of continuous treatment, blood pressure had returned to normal and adrenal receptor concentrations in treated rats were not significantly different from controls (180 fmol/mg, s.e.m. = 11 and 203 fmol/mg protein s.e.m. = 14 respectively, 0.1>P>005). 2. Vascular reactivity, defined as the pressor response to exogenous angiotensin II, increased concurrently by 166 and 33% respectively. 3. In anaesthetized dogs (n= 8), captopril (1.5 mg/kg, i.v.) caused a fall in blood pressure, and urine bradykinin excretion increased from 1 08 (s.e.m.=0 14) to 1 64 μg/h (s.e.m.=0 33, P < 0 025) at 15 min. Renal blood flow increased significantly (P < 0 01) with no change in glomerular filtration rate, and there was no change in either renal venous or arterial blood bradykinin levels. 4. Thus, converting enzyme inhibition produces transient secondary changes in angiotensin receptors and vascular reactivity. Increased urine bradykinin probably reflects decreased catabolism of intrarenal bradykinin. The hypotensive effect of captopril may be due in part to raised levels of bradykinin in the kidney.     

Mediastinal and hilar fibrosis

A case is described of mediastinal and hilar fibrosis in a woman aged 22 years. The fibrotic mass compressed the lobar arteries as well as the veins of various lobes of both lungs. These large vessels as well as numerous smaller arteries and veins were to a large extent obstructed by organized thrombi. It seems likely that 3 years after the beginning of symptoms the fibrosing process was still active. The case provides some support for an immunopathological aetiology of this condition.