Particle therapy using carbon ions or protons as a definitive therapy for patients with primary sacral chordoma.

OBJECTIVE: This study retrospectively evaluated the efficacy and toxicity of particle therapy using carbon ions or protons for primary sacral chordomas. METHODS: We evaluated 23 patients with primary sacral chordoma treated with carbon ion therapy (CIT) or proton therapy (PT) between July 2005 and June 2011 at the Hyogo Ion Beam Medical Center, Hyogo, Japan. The median patient age was 72 years. 14 patients were treated with 70.4 Gy equivalents (GyE) in 16 fractions and 9 were treated with 70.4 GyE in 32 fractions. CIT was used for 16 patients, and PT was used for 7 patients. RESULTS: The median follow-up period was 38 months. At 3 years, local control (LC), overall survival (OS) and progression-free survival (PFS) for all patients were 94%, 83% and 68%, respectively. The log-rank test revealed that male sex was significantly related to better PFS (p=0.029). No other factors, including dose fractionation and ion type, were significant for LC, OS or PFS. In nine patients, ≥ Grade 3 acute dermatitis was observed, and ≥ Grade 3 late toxicities were observed in nine patients. The 32-fraction protocol reduced severe toxicities in both the acute and late phases compared with the 16-fraction protocol. CONCLUSION: Particle therapy for patients with sacral chordoma showed favourable LC and OS. Severe toxicities were successfully reduced by modifying the dose fractionation and treatment planning in the later treatment era. Thus, this therapeutic modality should be considered useful and safe. ADVANCES IN KNOWLEDGE: This is the first study including both CIT and PT for sacral chordomas.

Particle therapy for mucosal melanoma of the head and neck. A single-institution retrospective comparison of proton and carbon ion therapy.

PURPOSE: To retrospectively analyze treatment outcomes after particle therapy using protons or carbon ions for mucosal melanoma of the head and neck (HNMM) at the Hyogo Ion Beam Medical Center, as well as to compare proton therapy (PT) and carbon ion therapy (CIT). PATIENTS AND METHODS: Data from 62 HNMM patients without metastasis, treated with PT or CIT between October 2003 and April 2011 were analyzed. Median patient age was 70.5 years (range 33-89 years). Of the total patients, 33 (53 %) had received PT and 29 (47 %) had undergone CIT. Protocols for 65 or 70.2 GyE in 26 fractions were used for both ion types. RESULTS: Median follow-up was 18.0 months (range 5.2-82.7 months). The 1-/2-year overall survival (OS) and local control (LC) rates were 93 %/61 % and 93 %/78 % for all patients, 91 %/44 % and 92 %/71 % for the PT patients and 96 %/62 % and 95 %/59 % for the CIT patients, respectively. No significant differences were observed between PT and CIT. Local recurrence was observed in 8 patients (PT: 5, CIT: 3) and 29 (PT: 18, CIT: 11) experienced distant metastases. Acute reactions were acceptable and all patients completed the planned radiotherapy. Regarding late toxicity, grade 3 or greater events were observed in 5 patients (PT: 3, CIT: 2), but no significant difference was observed between PT and CIT. CONCLUSION: Our single-institution retrospective analysis demonstrated that particle therapy for HNMM achieved good LC, but OS was unsatisfactory. There were no significant differences between PT and CIT in terms of either efficacy or toxicity.

[Influence of age on cardiac pump function during laparoscopic cholecystectomy--measurements by ear densitography].

Using ear densitography, consisting of photoelectric plethysomography and Holter electrocardiography, we measured systolic time intervals (STI) in 21 patients, ASA class 1 and 2, undergoing laparoscopic cholecystectomy using CO2 insufflation under general anesthesia (neuroleptanesthesia with isoflurane in air, FIO2 0.5). The patients were divided into two groups: Y-group (10 patients under 59 years of age) and O-group (11 patients over 60 years of age). We investigated the influence of age on cardiac pump function during pneumoperitoneum non-invasively. Y-group showed improvement of cardiac pump function (reduction of PEP/LVET) from 30 minutes after the beginning of insufflation and quick recovery of cardiac function immediately after deflation. O-group showed a tendency of increasing PaCO2 and arterial diastolic pressure, and delayed recovery of cardiac function (elongation of PEP at 60 minutes, and increase of PEP/LVET at 60 and 90 minutes, respectively, after insufflation). Hypertension and tachycardia were apparent immediately after pneumoperitoneum in the O-group. We conclude that special care and monitoring are mandatory for the aged patients with impaired cardiac or respiratory function during laparoscopic surgery.

[Effects of morphine, buprenorphine and butorphanol on airway dynamics of the rabbit].

An investigation was made on the effects of morphine, buprenorphine, and butorphanol on airway dynamics with special reference to the airway smooth muscle in rabbits. After tracheostomy under anesthesia, the animals were ventilated with a Servo 900B ventilator, and airway resistance (R) and total compliance (C) were measured according to the method of Norlander, and the effect of each drug was examined. Intravenous injection of morphine 0.2 mg.kg-1 increased R significantly at 10 and 20 minutes after its administration in nontreated animals and changed R insignificantly in animals pretreated with intravenous administration of chlorpheniramine 2.5 mg, an antihistaminic. It is considered that the increase in R after the administration of morphine in the nontreated animals is due to histamine release. Buprenorphine 0.8 micrograms.kg-1 and butorphanol 0.1 mg.kg-1 brought no significant changes in R in both nontreated and the chlorpheniramine pretreated animals. C decreased in all the groups including the control group which received mechanical ventilation alone without any drug administration.

Effects of verapamil on histamine-induced changes in lung mechanics.

The effects of verapamil on airway resistance and total thoracic compliance were studied in 15 rabbits with histamine-induced changes in lung mechanics. The animals, after being tracheotomized under anaesthesia, were subjected to mechanical ventilation in a time-cycled, volume-limited mode. Airway pressure and gas flow signals measured by a pneumotachograph and integrated for volume, were registered on a recorder. Each animal was given histamine hydrochloride in an isotonic solution of sodium chloride at a rate of 0.05 micrograms.kg-1.min-1 through a peripheral venous line. Verapamil was infused intravenously in an isotonic solution of sodium chloride at a rate of 20 micrograms.kg-1.min-1 after the initiation of histamine. Verapamil reduced the histamine-induced increase in airway resistance by 20% at 20 min after the start of administration.

[Analgesic effects of epidural morphine, fentanyl and lidocaine].

The analgesic effects of epidurally administered morphine 5 mg (group M, n = 15), fentanyl 100 micrograms (group F, n = 15), 2% lidocaine 60 mg (group L, n = 15) and normal saline (group S, n = 10) were investigated in 55 patients scheduled for abdominal surgery. Each drug was prepared in 3 ml solution and was injected though an epidural catheter introduced 3 cm cephalad into the epidural space at T10-11. Analgesic effects were assessed by changes in the dull pain sensation induced by electrical stimulation at 3 Hz through a pair of stainless needles which were placed subcutaneously at T7 and T10 dermatomes. In group M, analgesic effects at T10 were demonstrated in 12 of 15 subjects and the onset of analgesia was more rapid at T10 than at T7. The mean onset time of analgesia was 7.8 +/- 3.6 (mean +/- SD) min. There were 5 subjects in group F and 6 in group L who showed more rapid onset of analgesic effects at T10 than at T7, respectively. There were 2 subjects in group F and 5 in group L, with more rapid onset of analgesia at T7 than at T10. There were several subjects in group F and L with simultaneous onset of analgesia at T7 and T10. In group L, the mean distribution of analgesic area, confirmed with pinprick, was 5.2 +/- 1.9 (mean +/- SD) dermatomal segments. Hypercapnea, associated with somnolence, was frequently seen in group F. None of the subjects in group M, L or S showed such incidents. These results suggest that the main site of action of epidural morphine is located in the spinal cord while that of epidural fentanyl in the brain.

[Deterioration of oxygenation with mechanical ventilation, the lung time constant and cardiac output].

The influence of the lung time constant (tc) and preset volume on a ventilator-cardiac output ratio (Vv/Q) on the decrease in the oxygenation of blood (PaO2/FiO2) due possibly to mechanical controlled ventilation, was examined with special reference to the time of passive expiration in 18 patients. The degree of deterioration of oxygenation appeared to depend mainly on the time following FRC, during which the blood continued to perfuse the lungs until the next active insufflation by the ventilator. The characteristics of the negative exponential function indicated that the lungs theoretically were passively evacuated by 98% at tc x 4 (= TC) sec. The value for the expiratory time-TC/TC was 3. 7 +/- 1.3 before reduction of this expiratory time. Following reduction, 11 subjects showed improved oxygenation while no change was noted in the other 7. In the former Vv/Q was 1.19 +/- 0.21 and in the latter 0.94 +/- 0.03 before reduction, showing significantly smaller values in the latter (p less than 0.01). Within each of the four [(expiratory time-TC)/TC]/Vv/Q zones between 1.0 and 5.0 (1.0-2.0, 2.0-3.0, 3.0-4.0, 4.0-5.0), Vv/Q of those who showed no change in oxygenation was always less than Vv/Q of those who showed improved oxygenation (p less than 0.01). Thus, it is possible that a relatively prolonged exhalation time compared to the lung time constant, under the conditions of cardiac output dominance in Vv/Q, could be one of the causes of deterioration of oxygenation which occurs frequently during mechanically controlled ventilation.

[Relationship between molecular structure of halogenated methane compounds and their hypotensive effect in rats].

In this study gases of twelve halogenated methane compounds were administered by inspiration to Wistar rats in order to elucidate the relationship between molecular structure of the compounds and their hypotensive effect, and to develop new inhalational circulatory control agents. The correlation between the hypotensive effect of the compounds evaluated from the experimental data and computed van der Waals volume as well as surface area following molecular mechanics calculations of structure and energy, was investigated. The results showed that the compounds with van der Waals volume and surface area more than 73 A3 and 100 A2, respectively, had the hypotensive effect. In conclusion, our data suggest that the hypotensive effect of inhalational agents requires greater molecular sizes than regular ones.

Treatment of pigmentation of the lips and oral mucosa in Peutz-Jeghers' syndrome using ruby and argon lasers.

Three patients with punctate pigmented spots on the lips and oral mucosa, accompanying the P-J Syndrome, were successfully treated with ruby and argon lasers. The basic principles of laser treatment, the characteristics of the different laser systems and the skin reaction to ruby and argon lasers are discussed.