Imaging findings of radiation-induced sarcoma of the head and neck.

We set out to retrospectively review the clinical and imaging features of patients with post-radiation sarcoma, especially in the head and neck region. We reviewed the records of 4194 patients with carcinoma of the head and neck region who had a history of radiation. They had undergone CT and/or MRI. Medical records were reviewed for the primary diagnosis, radiation history and latency period to the development of sarcoma. The patients included four men and two women with a mean age of 64.5 years. The mean latency period for the development of sarcoma was 11.5 years. Primary diagnoses were maxillary carcinoma, nasopharyngeal carcinoma, adenoid cystic carcinoma of the oral floor, tonsilar carcinoma, soft palate carcinoma and tongue carcinoma. Histopathological examinations revealed osteosarcoma, spindle cell sarcoma, chondrosarcoma, malignant peripheral nerve sheath tumour, spindle cell carcinoma and malignant fibrous histiocytoma, respectively. Common findings were a heterogeneous and well-enhanced soft tissue mass and bone destruction. There is at present little or no prospect for the effective prevention of radiation-induced sarcoma of the head and neck. This emphasizes the importance of the earliest possible diagnosis for such patients. The imaging findings are not diagnosis specific, but strict follow-up within the radiation field by CT and MRI and an appreciation of the expected latency period may help to provide the diagnosis. When radiotherapy is performed for head and neck neoplasms, periodic follow-up observations may be necessary for many years.

Contrasting effects of dopamine therapy in experimental brain injury.

Management of cerebral perfusion pressure (CPP) is thought to be important for the treatment of traumatic brain injury (TBI). Vasopressors have been advocated as a method of increasing mean arterial blood pressure (mABP) and cerebral perfusion pressure (CPP) in the face of rising intracranial pressure (ICP). There are unresolved issues and theoretical risks about this therapy. This study therefore examined the effects of dopamine on physiological and MRI/MRS parameters in (1) a rodent model of rapidly rising intracranial pressure, caused by diffuse injury with secondary insult and (2) a model of cortical contusion. Dopamine was capable of restoring CPP in the model of rapidly rising ICP. This CPP restoration was associated with a partial restoration of CBF. Two profiles of change in the Apparent Diffusion Coefficient of water (ADCw) were seen; one in which ADCw recovered to baseline, and one in which ADCw remained persistently low. Dopamine did not alter these profiles. MRI assessed tissue water content was increased four hours after injury and dopamine increased cerebral water content in both subgroups of injury; significantly in the group with a persistently low ADCw (p < 0.01). In contusional injury, dopamine significantly worsened edema in both the ipsi- and contralateral hippocampus and temporal cortex. This occurred in the absence of ADCw changes, except in the contralateral hippocampus, where both water content and ADCw values rose with treatment, suggesting extracellular accumulation of water. In conclusion, although dopamine is capable of partially restoring CBF after injury, situations exist in which dopamine therapy worsens the swelling process. It is possible therefore that subgroups of patients exist who experience adverse effects of vasopressor treatment, and consequently the effects of vasopressor therapy in the clinical setting need to be more carefully evaluated.

The permissive nature of blood brain barrier (BBB) opening in edema formation following traumatic brain injury.

The contribution of blood brain barrier opening to traumatic brain edema is not known. This study compares the course of traumatic BBB disruption and edema formation, with the hypothesis that they are not obligately related. Sprague-Dawley rats were divided into three groups: Group A (n = 47)--Impact Acceleration (IAM); Group B (n = 104)--lateral cortical impact (CCI); Group C (n = 26)--IAM + hypoxia & hypotension (THH). BBB integrity was assessed using i.v. markers (Evan's Blue, or gadolinium-DTPA). Edema formation was evaluated with gravimetry, and T1-weighted MRI. In IAM, BBB opened immediately but closed rapidly, and remained closed for at least the next 36 hours whilst 24-hour hemispheric water content (HWC) rose by 0.9% (p < 0.01). In CCI, BBB opened in both hemispheres for up to 4 hours; four hour HWC in the uninjured hemisphere was indistinguishable from Sham, where HWC in the injured hemisphere rose by approximately 1.5% (p < 0.005). We distinguished two THH animals based on Apparent Diffusion Coefficient (ADC) recovery: in ADC-recovery animals 4 hour cortical water content (CWC) was 80.4 +/- 0.6%, cf 81.4 +/- 1.3% in ADC-non-recovery (p < 0.05). In all animals the BBB was open, however two populations of permeability were seen which likely related to flow-limited extravasation of gadolinium. In IAM edema forms despite only brief BBB opening. Although there is diffuse BBB opening with lateral contusion, edema only forms in the injured hemisphere. In THH, edema formation in the face of a widely permeable barrier is driven by ADC changes or cell swelling. Edema formation clearly does not correspond with BBB opening and an open BBB is clearly not required for edema formation. However we hypothesize that a permeable BBB permissively worsens the process, by acting as a low resistance pathway for ion and water movement. These findings are consistent with our general hypothesis that edema formation after TBI is mainly cytotoxic.

The effects of dopamine on edema formation in two models of traumatic brain injury.

The risk of vasopressors worsening cerebral edema has been raised. Previously we have reported that dopamine was able to restore cerebral blood flow in a model of monotonically rising intracranial pressure. In this study the effects of dopamine on cortical contusion and diffuse injury with secondary insult are examined. Adult male rats were divided into two groups: group 1 (n = 32)--Impact Acceleration Injury (IAM) with 30 minutes hypoxia and hypotension; group 2 (n = 12)--controlled cortical impact (6.0 m/sec, 3 mm depth). Dopamine was administered 2 hours post-injury (10-60 micrograms/kg/min i.v.). Cerebral water content and apparent diffusion coefficients (ADC) values were measured at baseline and four hours post-injury using MRI. Preinjury water content was the same in each group. Group 1 was subdivided into Groups 1A & 1B based on the ADC profile. Post-injury water content in Group 1A did not differ between saline or dopamine treated animals. Water content was higher in Group 1B-dopamine (83.4 +/- 1.1%) than Group 1B-saline animals (81.4 +/- 1.3%, p = 0.006). Contusion caused significant edema formation, however there was no significant difference between the dopamine treated or untreated group when considering either ipsilateral or contralateral cortex. Dopamine however significantly worsened edema in ipsilateral and contralateral hippocampus and both temporal cortices. ADC remained unchanged except in the contralateral hippocampus where both water content and ADC rose with dopamine suggesting precipitation of a vasogenic edema. In this study dopamine clearly worsened edema formation in two models of traumatic brain injury, and we conclude that there may be analogous clinical situations; therefore pressors should not be considered a 'blanket' therapy for all patients with a low cerebral perfusion pressure.

Atrial ectopy originating from the posteroinferior atrium during radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia.

Atrial ectopy sometimes appears during RF ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT). However, its origin, characteristics, and significance are still unclear. To examine these issues, we analyzed 67 consecutive patients with AVNRT (60 with slow-fast AVNRT and 7 with fast-slow AVNRT), which was successfully eliminated by RF ablation to the sites with a slow potential in 63 patients and with the earliest activations of retrograde slow pathway conduction in 4 patients. During successful RF ablation, junctional ectopy with the activation sequence showing H-A-V at the His-bundle region appeared in 52 patients (group A) and atrial ectopy with negative P waves in the inferior leads preceding the QRS and the activation sequence showing A-H-V at the His-bundle region appeared in 15 patients (group B). Atrial ectopy was associated with (10 patients) or without junctional ectopy (5 patients). Before RF ablation, retrograde slow pathway conduction induced during ventricular burst and/or extrastimulus pacing was more frequently demonstrated in group B than in group A (9/15 [60%] vs 1/52 [2%], P < 0.001). Successful ablation site in group A was distributed between the His-bundle region and coronary sinus ostium, while that in group B was confined mostly to the site anterior to the coronary sinus ostium. In group B, atrial ectopy also appeared in 21% of the unsuccessful RF ablations. In conclusion, atrial ectopy is relatively common during slow pathway ablation and observed in 8% of RF applications overall and 22% of RF applications that successfully eliminated inducible AVNRT. Atrial ectopy appears to be closely related to successful slow pathway ablation among patients with manifest retrograde slow pathway function.

Acute myocardial infarction and increased soluble intercellular adhesion molecule-1: a marker of vascular inflammation and a risk of early restenosis?

BACKGROUND: Plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been shown to predict activities of inflammatory disorders and malignancies. However, it is unknown whether the plasma level of sICAM-1 is increased in patients with acute myocardial infarction (AMI) with coronary intervention and whether the levels have any diagnostic or predictive values for vascular disease activity in patients with AMI. METHODS: We prospectively observed the time course of the plasma sICAM-1 levels in 20 patients with AMI whose infarct-related coronary artery was successfully recanalized by emergency balloon angioplasty. sICAM-1 was measured by enzyme-linked immunoassay. RESULTS: At admission, 48 hours, 1 week, and 2 weeks after angioplasty, sICAM-1 levels were significantly elevated in patients who had early (3 weeks) restenosis develop compared with those who did not (p < 0.05). At the other time points examined, there was a tendency of higher sICAM-1 levels in patients with than without restenosis (0.06 < p < 0.09). The relation of sICAM-1 levels and total white blood cell counts, neutrophil counts, or numbers of diseased major coronary artery branches was not statistically significant. CONCLUSIONS: A persistent increase in plasma sICAM-1 levels may indirectly implicate vascular inflammation, which could predict the risk of early coronary restenosis after emergency angioplasty in patients with AMI. Hence, measurements of sICAM-1 in patients with AMI would serve as a potentially useful predictor of the risk of early postangioplasty restenosis.

Contribution of vasogenic and cellular edema to traumatic brain swelling measured by diffusion-weighted imaging.

The contribution of brain edema to brain swelling in cases of traumatic brain injury remains a critical problem. The authors believe that cellular edema, the result of complex neurotoxic events, is the major contributor to brain swelling and that vasogenic edema, secondary to blood-brain barrier compromise, may be overemphasized. The objective of this study, therefore, was to quantify temporal water content changes and document the type of edema that forms during the acute and late stages of edema development following closed head injury (CHI). The measurement of brain water content was based on magnetic resonance imaging-determined values of tissue longitudinal relaxation time (T1-weighted imaging) and their subsequent conversion to percentage of water, whereas the differentiation of edema formation (cellular vs. vasogenic) was based on the measurement of the apparent diffusion coefficient (ADC) by diffusion-weighted imaging. A new impact-acceleration model was used to induce CHI. Thirty-six adult Sprague-Dawley rats were separated into two groups: Group I, control (six animals); and Group II, trauma (30 animals). Fast ADC measurements (localized, single-voxel) were obtained sequentially (every minute) up to 1 hour postinjury. The T1-weighted images, used for water content determination, and the diffusion-weighted images (ADC measurement with conventional diffusion-weighted imaging) were obtained at the end of the 1st hour postinjury and on Days 1, 3, 7, 14, 28, and 42 in animals from the trauma and control groups. In the animals subjected to trauma, the authors found a significant increase in ADC (10 +/- 5%) and brain water content (1.3 +/- 0.9%) during the first 60 minutes postinjury. This is consistent with an increase in the volume of extracellular fluid and vasogenic edema formation as a result of blood-brain barrier compromise. This transient increase, however, was followed by a continuing decrease in ADC that began 40 to 60 minutes postinjury and reached a minimum value on Days 7 to 14 (10 +/- 3% reduction). Because the water content of the brain continued to increase during the first 24 hours postinjury (1.9 +/- 0.9%), it is suggested that the decreased ADC indicated cellular edema formation, which started to develop soon after injury and became dominant between 1 and 2 weeks postinjury. The study provides supportive evidence that cellular edema is the major contributor to posttraumatic swelling in diffuse CHI and defines the onset and duration of the increase in cellular volume.

Tissue factor expression on macrophages in coronary plaques in patients with unstable angina.

Tissue factor is a membrane-bound glycoprotein that functions in the extrinsic pathway of blood coagulation by acting as a cofactor for factor VII, and the resulting complex leads to thrombin production in vivo. The purpose of the present study is to determine whether macrophages express tissue factor in human coronary atherosclerotic plaques. We examined directional coronary atherectomy specimens from 24 patients with unstable angina and 23 with stable exertional angina. In these specimens, macrophages were detected in 22 (92%) of 24 patients with unstable angina versus 12 (52%) of 23 with stable exertional angina (P = .003). The percentage of macrophage infiltration area was significantly larger in patients with unstable angina than in those with stable exertional angina (17 +/- 3% versus 6 +/- 2%, P = .008). The immunohistochemical double staining revealed the expression of tissue factor on macrophages in 18 (75%) of 24 patients with unstable angina versus 3 (13%) of 23 with stable exertional angina (P < .0001). Thrombus was identified in 20 (83%) of 24 patients with unstable angina versus 12 (52%) of 23 with stable exertional angina (P = .02). Fibrin deposition was mainly observed around macrophages expressing tissue factor in the patients with unstable angina. We have shown that tissue factor expression on macrophages was more frequent in coronary atherosclerotic plaques in patients with unstable angina. Tissue factor expressed on macrophages may play an important role in the thrombogenicity in coronary atherosclerotic plaques of these patients.

Increased plasma soluble intercellular adhesion molecule-1 levels in patients with acute myocardial infarction.

Intercellular adhesion molecule-1 (ICAM-1) is a major ligand for 2 members of the CD18 family of leukocyte integrin adhesion molecules and mediates adhesion between leukocytes and stimulated endothelial cells. We examined plasma soluble ICAM-1 (sICAM-1) levels in 30 patients with acute myocardial infarction (AMI) within 6 h of symptom onset, 21 patients with unstable angina (UA), 35 patients with stable exertional angina (SEA) and 21 control subjects. Plasma sICAM-1 levels (ng/ml) were significantly higher in both the acute and chronic phases of AMI and in the UA group than in the SEA and the control groups (195 +/- 14, 198 +/- 16 in the acute and chronic phases of AMI, 188 +/- 11 in the UA group vs 142 +/- 7 in the SEA group, 141 +/- 10 in the control group, p < 0.01). Plasma sICAM-1 levels were significantly higher in AMI patients when preceded by unstable angina than when not preceded by unstable angina at any point over the time course except 1 week after admission (p < 0.01 vs admission, 12 h, 2 days, 3 days, 5 days, 2 weeks, 3 weeks. p < 0.05 vs 24 h). These results suggest that the increase in sICAM-1 is associated with repeated episodes of myocardial ischemia and reperfusion not leading to myocardial necrosis. The increase in sICAM-1 may play an important role as an inflammatory component in the pathogenesis of the ischemic myocardium.

Serum levels of vascular endothelial growth factor in patients with acute myocardial infarction undergoing reperfusion therapy.

1. Vascular endothelial growth factor, a potent angiogenic mitogen, is known to be induced in response to ischaemia as well as being secreted from tumour cells. However, the precise mechanism of vascular endothelial growth factor release in acute myocardial infarction and the effects of coronary reperfusion on the circulating levels of vascular endothelial growth factor are still unknown. 2. Nineteen patients with acute myocardial infarction who underwent early reperfusion therapy were studied. Serum levels of vascular endothelial growth factor before reperfusion were markedly increased as compared with those in 19 healthy control subjects [252.4 +/- 158.1 pg/ml (mean +/- SD) compared with undetectable]. After reperfusion, the serum vascular endothelial growth factor levels rapidly returned almost completely to the normal control range. 4. These data strongly suggest that the serum level of vascular endothelial growth factor is one of the most sensitive indicators of myocardial ischaemia.

Detection of brain atrophy following traumatic brain injury using gravimetric techniques.

We hypothesized, that with atrophy, the correlation between water content and specific gravity of brain solids would break down signifying the onset of the atrophic process. The correlation between tissue water content, specific gravity of solids and ventricular size was studied in an impact acceleration model of closed head injury of the rat. Adult Sprague Dawley rats weighing 350 to 375 grams (n = 63) were separated into two groups: Group 1: Sham (n = 21), Group II: Trauma (n = 42). Water content was assessed using both gravimetric method and drying-weighing method at 1 hour, on days 1, 3, 7, 14, 28, and 42 in the trauma group as well as in the control group. Ventricular size was measured in cm2 on the MRI computer console in the coronal section at the coronal suture at the same time points. In the trauma group we found a significant increase (p < 0.01) in water content during the first week except on day 3 and there was a good correlation between the results of water content using both methods (p < 0.001). However, this relationship was poorly correlated after day 14 (p = 0.25). Although the ventricular size was the smallest at 1 hour post trauma, it significantly increased over the next 3 days (p < 0.001). On day 7 and 14 ventricular size decreased to normal size, yet gradually increased and then reached a significantly larger size on 42 days post trauma again (p < 0.01). We may consider, that brain edema following CHI begins immediately following trauma and resolves within 2 weeks. After 14 days degenerative change occurs in the cortex, as detected by specific gravity measurements which signifies the onset of the atrophic process and subsequent post traumatic ventricular dilatation.

Biphasic pathophysiological response of vasogenic and cellular edema in traumatic brain swelling.

The objective of this study was to quantify the temporal water content changes and document the type of edema (cellular versus vasogenic) that is occurring during both the acute and the late stages of edema development following closed head injury. Adult Sprague rats (n = 50) were separated into two groups: Group I: Sham (n = 8), Group II: Trauma (n = 42). The measurement of brain water content (BWC) was based on T1, whereas the differentiation of edema on the measurement of the random, translational motion of water protons (apparent diffusion coefficients-ADC) by MRI. In trauma animals, we found a significant increase in ADC (105%) as well as in BWC (0.7 +/- 0.3%) during the first 60 minutes post injury indicating vasogenic edema formation. This transient increase; however, was followed by a continuing decrease in ADC beginning at 45 minutes post injury and reaching a minimum at days 7-14 (-103%). Since the BWC continued to increase during the next day (10.3%), it is suggested cellular edema formation started to develop soon after injury and became dominant between 1-2 weeks post injury. In conclusion we may consider, that there is a predominantly vasogenic edema formation immediately after injury and later a more widespread and slower edema formation due to a predominantly cellular swelling.

[Effect of thrombolysis on rupture of the left ventricular free wall following acute myocardial infarction].

Rupture of the left ventricular free wall is one of the most serious sequels of acute myocardial infarction (AMI) and results in hospital death. The effectiveness of thrombolytic therapy for AMI to prevent rupture of the left ventricular free wall was studied retrospectively in 31 patients (2.6%) among 1,210 consecutive patients admitted to our hospital within 48 hours after the onset of AMI. All patients were divided into three groups: 758 without reperfusion therapy (conventional group), 113 who underwent direct percutaneous transluminal coronary angioplasty (direct PTCA group), and 339 who received thrombolytic therapy with or without PTCA (thrombolysis group). No rupture was found in the direct PTCA group. No significant difference could be found in the incidence of the rupture between the conventional group (19 patients, 2.5%) and the thrombolysis group (12 patients, 3.5%). When early rupture and late rupture are defined as occurring less and more than 48 hours from the onset of AMI, 14 early ruptures (1.8%) and 5 late ruptures (0.7%) were found in the conventional group, and 9 early ones (2.7%) and 3 late ones (0.9%) in the thrombolysis group. There was no significant statistical difference between the two groups. The incidence of the rupture according to the result of the reperfusion therapy was much higher in the unsuccessful group (five patients, 7.8%; p < 0.02) than in the successful group (seven patients, 2.5%; p < 0.002). All ruptures in the successful group appeared early; but only two early rupture cases (3.1%) out of five were found in the unsuccessful group. The mean interval between the thrombolysis and the rupture was 3.9 +/- 1.2 hours in the successful group, which was much shorter than that of the unsuccessful group (67.1 +/- 28.5 hours; p < 0.05). We conclude that thrombolytic therapy, if successful, may be effective to decrease late rupture of the left ventricular free wall, but may be ineffective to prevent early rupture.

Effects of angiotensin-converting enzyme inhibitor alacepril in patients with stable effort angina during chronic isosorbide dinitrate treatment.

Nitrate tolerance has been reported to be reversed by certain types of angiotensin-converting enzyme (ACE) inhibitors. We examined whether alacepril, a new long-acting oral ACE inhibitor, has beneficial effects against exercise-induced angina in patients with stable effort angina after substantial isosorbide dinitrate (ISDN) treatment. Thirteen men with stable effort angina were treated with oral ISDN (80 mg/d) for >3 weeks. After this period, efficacy of single oral administration of either alacepril (50 mg) or its placebo on exercise-induced angina and electrocardiographic changes was examined by treadmill exercise test in a double-blind crossover design. Alacepril significantly improved the exercise duration by 9.1% (p=0.03), the time to 1 mm ST-segment depression by 19% (p<0.01), and the maximal ST-segment depression by 33% (p=0.015) compared with placebo. Alacepril did not significantly alter the rate-pressure product, a marker of myocardial oxygen demand, during exercise test compared with placebo. Plasma renin activity was significantly increased (p<0.05) after administration of alacepril, indicating that alacepril significantly blocked ACE activity in our patients. In conclusion, a single oral administration of the ACE inhibitor alacepril (50mg) elicited beneficial effects against exercise-induced myocardial ischemia in patients with stable effort angina during chronic nitrate treatment. These effects may be mediated by increased coronary blood flow.

Augmented sympathoadrenal activity during treadmill exercise in patients with Wolff-Parkinson-White syndrome and atrial fibrillation.

It is believed that reciprocating tachycardia and accessory pathways play important roles in atrial fibrillation (AF) in patients with Wolff-Parkinson-White (WPW) syndrome. However, the mechanism by which AF occurs is not yet fully understood. This study was performed to evaluate the contribution of sympathoadrenal activity to the onset of AF in patients with WPW syndrome. Symptom-limited treadmill exercise testing was performed and plasma norepinephrine and epinephrine concentrations were measured simultaneously in 27 patients with WPW syndrome and 20 control subjects. In 13 patients with WPW syndrome and AF, plasma norepinephrine and epinephrine concentrations increased to 3.69 +/- 2.44 and 0.76 +/- 0.69 ng/ml at maximum exercise, respectively. These values were significantly higher (p < 0.001) than those in control subjects and in patients without AF. Pretreatment with 0.2 mg/kg of propranolol significantly reduced the incidence of exercise-induced atrial premature complexes (chi 2 = 7.33, p < 0.05). With oral beta-blockade for an average of 22.8 months, the incidence of AF decreased significantly from 1.77 +/- 0.53/patient per year to 0.33 +/- 0.57/patient per year (p < 0.001). Augmented sympathoadrenal activity in patients with WPW syndrome may contribute to AF.

Effects of antecedent anginal episodes and coronary artery stenosis on left ventricular function during coronary occlusion.

We evaluated the effects of antecedent anginal episodes and coronary artery stenosis on left ventricular function during coronary occlusion and the role of collateral filling in 33 patients with angina pectoris who underwent angioplasty. Wall motion abnormalities were investigated by echocardiography and classified into hypokinesia and akinesia. Collateral filling during angioplasty was evaluated by using a second artery catheter. Akinesia was observed as follows: 24% of the patients had > 30 anginal episodes, 38% had 5 to 30, and 87% of the patients had < 5 (p < 0.01); 12% of patients had a lesion of 99%, 47% had a lesion of 90%, and 83% had a lesion of 75% (p < 0.05). Akinesia was observed in none of the patients with grade 3 collaterals, 57% with grade 2, and 67% with grade 1 or 0 (p < 0.01). These observations suggest that the patients with antecedent frequent anginal episodes and severe coronary stenosis have less left ventricular dysfunction during coronary occlusion. This finding may be the result of more extensive collateral development.

Right ventricular wall motion disturbance and determinants of the appearance of hemodynamic right ventricular infarction.

In order to elucidate the mechanisms of the appearance of hemodynamic right ventricular infarction (RVI), we studied right and left ventriculograms and hemodynamic findings in 52 patients with acute inferior myocardial infarction. Right ventricular wall motion disturbance (RVWMD) was detected in 69% of patient but hemodynamic RVI was observed only in 16%. Among patients with RVWMD, there was no significant difference in right ventricular ejection fraction between those with (group III) and without (group II) hemodynamic RVI, suggesting that right ventricular (RV) systolic dysfunction does not independently produce hemodynamic RVI. Right ventricular end-diastolic volume index was similar in groups II and III in spite of higher mRA in group III. The result suggested that the RV compliance of group III was decreased. Heart rate (HR) was significantly lower in group III than in group II. Not only physiologic pacing but also VVI pacing significantly improved hemodynamics in patients with hemodynamic RVI. A positive correlation between HR and cardiac index was observed (r = 0.56, p < 0.001) in patients with RVWMD. Decreased RV compliance and bradycardia were considered to be determinants of the appearance of hemodynamic RVI. Volume loading did not improve hemodynamics significantly in patients with hemodynamic RVI.

[A late phase II clinical study of cis-diammine glycolato platinum, 254-S, for head and neck cancers].

A late phase II clinical study of 254-S, a new anticancer platinum complex, for head and neck cancer was conducted by the 254-S Head and Neck Cancer Study Group consisting of 31 institutions. As in the early phase II study for head and neck cancers, 254-S was administered at 100 mg/m2 by 60 min intravenous drip infusion, repeated at least twice at 4-week intervals. Of 80 cases registered, 66 were regarded as complete cases evaluable for tumor response. Complete response (CR) was observed in 7 patients (10.6%), partial response (PR) in 22 (33.3%), no change (NC) in 24 and progressive disease (PD) in 13, for a 43.9% response rate. Two CR and 11 PR (37.1% response rate) were obtained in 35 patients with prior chemotherapy, including 2 CR and 7 PR (33.3% response rate) in 27 patients previously treated with cisplatin. Of 70 patients evaluable for toxicity, side effects were observed in 60 patients (85.7%). Major toxic effects were hematotoxicity, including leukopenia (62.9%), thrombocytopenia (40.0%) and anemia (45.7%), gastrointestinal toxicity, including nausea and vomiting (64.3%), and anorexia (47.1%); grade 3 or 4 thrombocytopenia was found in 20.0% of the patients, and this toxicity was regarded as the dose limiting factor. Nephrotoxicity observed was mild and infrequent. Based on these results, it was concluded that 254-S is a very useful anticancer agent for the treatment of head and neck cancer.

[An early phase II clinical study of cis-diammine glycolato platinum, 254-S, for head and neck cancers].

An early phase II clinical study of 254-S, a new anticancer platinum complex, for head and neck cancer was conducted by the 254-S Head and Neck Cancer Study Group consisting of 10 institutions. Based on the results obtained in the phase I study, 254-S was administered at 100 mg/m2 by 60 min intravenous drip infusion after being dissolved in 300 ml of 5% xylitol. In principle, the 254-S administration was repeated at least 2 times at 4 week intervals. Hydration was performed, if needed. All 24 cases registered were regarded as complete cases evaluable for tumor response. Complete response (CR) was observed in 4 patients (16.7%), partial response (PR) in 5 (20.8%), no change (NC) in 11 and progressive disease (PD) in 4, for a 37.5% response rate. Three CR and 3 PR (40.0%) were obtained in 15 patients with prior chemotherapy, including 1 CR and 2 PR (33.3%) in 9 patients previously treated with cisplatin. Side effects were observed in 19 patients (79.2%). Major toxic effects were hematotoxicity, including thrombocytopenia (58.3%), leukopenia (58.3%) and anemia (33.3%), and gastrointestinal toxicity, including nausea and vomiting (45.8%) and anorexia (37.5%). Abnormal parameter changes on renal function were found in 2 patients (8.3%). Based on these results, it was concluded that 254-S is potentially a useful anticancer agent for the treatment of head and neck cancer, and should be further investigated in a late phase II clinical study.