Intensified preoperative chemoradiation by adding oxaliplatin in locally advanced, primary operable (cT3NxM0) rectal cancer : Impact on long-term outcome. Results of the phase II TAKO 05/ABCSG R­02 trial.

PURPOSE: The major goals of preoperative treatment for locally advanced rectal cancers (LARCs) are improvement of local tumor control, tumor downsizing, and downstaging. Modifications with respect to standardized chemoradiation protocol, e. g., integrating oxaliplatin, are realized with the aim of improving primary tumor response and patient outcome. PATIENTS AND METHODS: In this phase II multicenter study, patients with LARC of the mid- or lower rectum, cT3cNxcM0 as staged by MRI, were included and treated preoperatively with a combination of capecitabine and oxaliplatin following a standardized protocol during radiation. The focus of this long-term analysis was overall (OS) and disease-free survival (DFS). RESULTS: A total of 60 patients (19 women, 41 men, median age 60.5 years) were initially enrolled, 1 patient was excluded (violation of study protocol), and 1 was patient lost of follow-up, leading to a total of 58 patients for long-term analysis. The 3­year OS was 85.5%; 3­year DFS 71.2%. Over time, 15 patients (25.9%) developed tumor recurrence (1 locoregional, 6.7%; 11 distant, 73.3%; 3 locoregional+distant, 20%). Recurrence-specific therapy was planned in the majority of patients, in 9 of 15 patients (60%) with a radical surgical approach. Of these, 4 patients (44.4%) are again tumor-free at the end of investigation. While tumor downsizing (T level) or pathologically complete response did not influence patient survival, lymph node negativity (LNneg) after preoperative chemoradiation showed significant influence. CONCLUSION: LNneg after preoperative treatment for LARC significantly influences patient survival. A radical surgical approach for recurrent LARC (locoregional, distant) should be contemplated when possible as we were able to clearly demonstrate its importance and efficacy.

Laterality of hand, foot, eye, and ear in twins.

Information on handedness, footedness, eyedness, and earedness was collected from 33 monozygotic (MZ) twin pairs and 67 dizygotic (DZ) twin pairs. The incidence of nonright-sidedness in the twins is not higher than that reported in the literature for singletons. Similar results are found for the other lateralities. The results of assessing handedness with preference tests do not differ from those carried out with performance tests. There are no differences in incidence of nonright-sidedness between MZ and DZ twins. The concordance of lateralities is similar in MZ and DZ twins. The proportions of Right-Right, Right-Nonright, and Nonright-Nonright pairs in both groups of twins show a binomial distribution. The present results do not confirm a genetic hypothesis of determination of sidedness in humans and are comparable with the results obtained by other twin studies.

Efficacy and safety of cilazapril in elderly patients with essential hypertension. A multicenter study.

The efficacy and safety of cilazapril monotherapy was evaluated in a multicenter, open-label, ascending-dose titration study in 83 elderly essential hypertensive patients. After a four-week, single-blind, placebo run-in period, patients received 1 mg of cilazapril once daily for the first four weeks. This dose was then increased to 2.5 mg once daily for the next four weeks for patients whose pre-dose sitting diastolic blood pressure was above 90 mm Hg. Similarly, at Week 8 the dose was increased in such patients from 1 to 2.5 mg or from 2.5 to 5 mg once daily. A 12-hour blood pressure profile was performed on the first day of active treatment and of each dose increase. Mean decrease of sitting diastolic blood pressure from baseline (102.7 +/- 0.4 mm Hg) at Week 12 was 13.3 +/- 1.1 mm Hg (p less than 0.001). Seventy-five percent of patients had a decrease of 10 mm Hg or more from baseline sitting diastolic blood pressure, and in 60 percent sitting diastolic blood pressure normalized. Unexpectedly large decreases of blood pressure after the first dose were seen only in three patients and none had clinical symptoms. Fourteen patients (16.9 percent) reported adverse events, but most of these were judged unlikely to be related to therapy. Four patients with predisposing underlying diseases experienced potentially serious adverse events (angina pectoris, myocardial infarction, arrhythmia, and blood pressure elevation) whose relationship to therapy was judged remote or only possible. There was no particular pattern of changes in laboratory values. The results indicate that cilazapril is an effective, safe, and well-tolerated antihypertensive drug for the elderly.

Cilazapril: a new non-thiol-containing angiotensin-converting enzyme inhibitor. Worldwide clinical experience in hypertension.

Cilazapril is a structurally new angiotensin-converting enzyme inhibitor that lacks a sulfhydryl moiety. Its duration of action is consistent with a once-daily regimen. Cilazapril was studied in multiple-dose trials that included more than 4,500 hypertensive patients worldwide. Approximately 450 patients received cilazapril as monotherapy for more than one year, and another 430 patients were treated with cilazapril in combination with hydrochlorothiazide for more than six months. Cilazapril at doses of 2.5 to 5 mg once daily is clinically and statistically significantly more effective than placebo and as effective after eight weeks of therapy as hydrochlorothiazide, atenolol, propranolol sustained release, captopril, and enalapril at the doses recommended by the manufacturers. The overall incidence of adverse events observed during cilazapril therapy is comparable with that seen with placebo in double-blind studies. Cilazapril 2.5 to 5 mg once daily seems to be better tolerated than hydrochlorothiazide and atenolol. Only five adverse events were reported at an incidence of 1 percent or more in controlled trials; these were headache, dizziness, fatigue, nausea, and chest pain, which all occurred at a frequency similar to that with placebo. Overall, cilazapril is effective and well-tolerated in the treatment of patients with hypertension.

Antihypertensive properties of tiapamil (RO 11-1781)--a new calcium antagonist--in patients with mild and moderate essential hypertension.

An open, non-comparative study, with a new calcium antagonist-tiapamil, was undertaken in 22 patients with mild and moderate essential hypertension (stage I-II WHO). After a two-week placebo period, patients were treated with tiapamil, 300-600 mg twice daily during a period of six weeks (Dose-finding period). Thereafter patients were continued on tiapamil during a 54 week period (Long-term follow-up). In some patients it was necessary to add the diuretic hydrochlorothiazide to obtain adequate control of the arterial hypertension. Monotherapy with tiapamil normalized supine diastolic blood pressure after the first six weeks in 17 of the 21 evaluable patients, and reduced it by greater than or equal to 10 mmHg (1.3 kPa) from baseline without normalization in two patients. In the two remaining cases the decrease was less than 10 mmHg. The optimal dose administered at six weeks in those patients who responded to treatment (normalization or decrease by greater than or equal to 10 mmHg.) was 600 mg/day in 32% of the cases, 750-900 mg/day in 47% and more than 900 mg/day in 21%. After completion of the dose-finding part, 19 patients continued treatment for a further 54 weeks. In 16 out of 19 patients hydrochlorothiazide was added to enhance the antihypertensive effect. All three patients who received tiapamil monotherapy throughout the trial, had normalized supine diastolic blood pressure on completing the study. In the 16 patients with the combination therapy, the addition of hydrochlorothiazide led in two patients to no further decrease in supine diastolic blood pressure, to an additional decrease by less than 10 mmHg in ten patients and by greater than or equal to 10 mmHg in four in comparison with the values obtained before starting combination therapy. At the end of the study 11 of these 16 patients had normalized supine diastolic blood pressure. The mean daily dose was 900 +/- 45 mg of tiapamil and 39 +/- 4 mg of hydrochlorothiazide. Both monotherapy and the combination regimen were well tolerated, and no effects attributable to drug interactions were observed. It may be concluded that tiapamil in oral doses of 300-600 mg twice daily is an effective antihypertensive agent with an excellent tolerance when administered for a period of 54 weeks.

Tiapamil and hydrochlorothiazide: a double-blind comparison of two antihypertensive agents.

Tiapamil is an investigational calcium-channel antagonist that is chemically related to verapamil. The antihypertensive efficacies of tiapamil and hydrochlorothiazide (HCTZ) were compared in a randomized double-blind trial. Thirty patients, age 44 to 80 years, with mild to moderate hypertension (World Health Organization stage I-II) entered and completed the study. Previous therapy, if any, was stopped for at least one week prior to study initiation, and patients received placebo tablets for two weeks. The participants were then given active medication, which was titrated for the next three weeks; HCTZ 25 to 50 mg bid or tiapamil 300 to 600 mg bid was given until supine diastolic blood pressure (BP) was no higher than 90 mm Hg or the ceiling dose was reached. Both drugs caused a significant reduction in systolic as well as in diastolic blood pressure (P less than .01). The reduction was seen in both the supine and erect position. The median decrease in supine systolic blood pressure from baseline to the end of treatment was 20 mm Hg in the tiapamil group and 27 mm Hg in the hydrochlorothiazide group, whereas the median decrease in supine diastolic blood pressure was 14 mm Hg and 18 mm Hg, respectively. The median difference in supine diastolic BP reduction after HCTZ and tiapamil administration was 3.8 mm Hg (not significant). There were no significant changes in heart rate. Dizziness occurred in one patient taking tiapamil and in three receiving HCTZ. One patient receiving HCTZ developed acute arthritis urica.(ABSTRACT TRUNCATED AT 250 WORDS)

Slipover urethral instrument system.

An inovative system has been devised using an elongated hollow guide and slipover urethral instruments. Inherent in this concept are many safety features. A slipover follower and sound will replace current instruments with the threaded locking mechanism. The versatility of the system is demonstrated by the passage of the Councill catheter, cystoscope and direct vision urethrotome over the guide. The orderly interaction of all instruments facilitates their use.