Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.     

Long thoracic nerve paralysis associated with thoracic outlet syndrome

Two cases of long thoracic nerve palsy associated with thoracic outlet syndrome are reported. Both patients had abnormal posture, with low-set shoulders and winged scapulae. Clinically there was weakness of the serratus anterior muscle with partial denervotion on electromyography. The diagnosis of thoracic outlet syndrome was based on positive vascular tests and brachial plexus nerve compression symptoms induced by the vascular testing positions. An orthosis that held the shoulder in an elevated position was used in both cases. Complete recovery of shoulder function and relief of the symptoms was achieved in both cases at 8 and 13 months, respectively, after application of the orthosis.     

Efficacy of an echo contrast agent, SH/TA-508, in color doppler sonography of mass lesions in urology

We performed a clinical phase III study with a galactosebased ecoo contrast agent, SH/TA-508, to evaluate its efficacy, safety, and usefulness for mass lesions in urology. SH/TA-508 was prepared as a suspension containing stabilized micro-air bubbles by adding water for injection just before use. SH/TA-508 was administered into the antecubital vein at an initial dose of 300 mg/ml × 5 ml followed by higher doses of 400 mg/ml × 4 ml, 300 mg/ ml × 10 ml or 400 mg/ml × 8 ml when a sufficient effect was not obtained. Efficacy was evaluated by color Doppler signal enhancement, the duration of blood flow signal enhancement, and improvement of diagnostic capacity. Fifty-nine patients with mass lesions in the kidney, prostate, testis, adrenal gland, and bladder were enrolled in the study. Up to the third dose the cumulative efficacy rates (≥2+) of color Doppler signal enhancement and duration of blood flow signal enhancement were 92% and 87%, respectively. Consequently, diagnostic capacity in 76% of the patients was remarkably improved. A light transient angialgia occurred in one patient but no other clinically significant changes were observed. It was confirmed that SH/TA-508 is a safe echo contrast agent that offers satisfactory color Doppler signal enhancement in the urologic organs mentioned above.     

Acquired pulmonary stenosis caused by mediastinal mature teratoma: a case report

A 13-year-old girl was admitted with a sudden onset of chest oppression. Mediastinal teratoma was suspected on chest X-ray and CT scan. A grade 2/6 systolic murmur was heard at the upper left sternal area and cardiac catheterization showed mild pulmonary stenosis. After resection of the tumor, the murmur disappeared and histopathological diagnosis was mature teratoma. This is a rare case report of pulmonary stenosis caused by mediastinal mature teratoma.     

Major organ function under mechanical support: comparative studies of pulsatile and nonpulsatile circulation

We examined a major organ function during 3 h biventricular assisted circulation after acute myocardial infarction model in the pig. In left ventricular circulation, the outflow cannula was placed in the ascending aorta and an inflow cannula through the mitral valve in the left ventricle. A pump (pulsatile group, Zeon Medical, Inc., Tokyo, Japan and nonpulsatile group, Nikkiso HPM-15, Nikkiso, Inc., Tokyo, Japan) was connected to each cannula. In right ventricular circulation, the outflow cannula was placed in the pulmonary artery and an inflow cannula in the right ventricle. The right ventricular circulation was supported by a nonpulsatile pump (Nikkiso HPM-15). The items measured were the regional blood flows of the cortex and medulla in the kidney, white matter and gray mater in brain, and liver; renal arterial flow; carotid arterial flow; portal vein flow; common hepatic arterial flow; arterial ketone body ratio (AKBR); and lactate/pyrubic acid (L/P). In the pulsatile group, the renal cortical blood flow increased, and the medulla blood flow decreased. On the other hand, in the nonpulsatile group, both regional blood flows decreased. That means that in the pulsatile assisted group intrarenal redistribution improved rather than in the nonpulsatile assisted group. In addition the liver regional blood flow, AKBR, and L/P showed significant differences between the pulsatile and nonpulsatile groups. On the other hand, the white matter and gray matter regional blood flows and carotid arterial flow did not show significant differences between the groups. The results of our study indicated that pulsatile circulation produced superior circulation in the kidney and liver, and microcirculation on the cell level was superior as well in early treatment of acute heart failure.     

Prevention of post-operative nausea and vomiting with combined granisetron and droperidol in women undergoing thyroidectomy

We have compared the efficacy and safety of combined granisetron and droperidol with each anti-emetic alone for preventing post-operative nausea and vomiting after thyroidectomy. In a prospective, randomized, double-blind study, 180 women received granisetron 40 micrograms kg-1, droperidol 20 micrograms kg-1, or granisetron 40 micrograms kg-1 plus droperidol 20 micrograms kg-1 (n = 60 of each) intravenously immediately before induction of anaesthesia. A standard general anaesthetic technique and post-operative analgesia were used. A complete response, defined as no post-operative nausea and vomiting and no need for another rescue anti-emetic, during the first 24 h after anaesthesia occurred in 88%, 60% and 98% of patients who had received granisetron, droperidol and granisetron plus droperidol (P < 0.05; overall Fisher's exact probability test). No clinically important adverse events due to the drugs were observed in any of the groups. In summary, prophylactic use of combined granisetron and droperidol is more effective than each drug alone for the prevention of post-operative nausea and vomiting in female patients undergoing thyroidectomy.     

Specific IgG to gelatin in children with systemic immediate- and nonimmediate-type reactions to measles, mumps and rubella vaccines.

We examined anti-gelatin IgG in sera of children who suffered from systemic adverse reactions upon immunization with gelatin-containing live virus vaccines. In the group of 30 children who had immediate-type reactions and anti-gelatin IgE, 30 (100%) had anti-gelatin IgG and 29 (96%) had anti-gelatin IgG4. In another group of 75 children who had nonimmediate-type reactions and no anti-gelatin IgE, 22 (29%) had anti-gelatin IgG and six (8%) had IgG4. The IgG positivity well correlated with the lymphocyte proliferation assay positivity. In contrast, as a negative control, all 24 children who had no allergic reaction to live virus vaccines had no anti-gelatin IgG and IgG4. The results suggest that immune-response to gelatin may play a role in the pathogenesis of systemic nonimmediate-type reactions to the live virus vaccines.     

The modulatory effect of (+)-TAN-67 on the antinociceptive effects of the nociceptin/orphanin FQ in mice

To clarify the pharmacological properties of (+)2-Methyl-4aalpha-(3-hydroxyphenyl)-1, 2, 3, 4, 4a, 5, 12, 12aalpha-octahydro-quinolino[2, 3, 3-g]isoquinoline ((+)-TAN-67), the effect of (+)-TAN-67 on the antinociception induced by the intrathecal (i.t.) administration of nociceptin/orphanin FQ was studied in mice using the tail-flick test and the formalin test. I.t. administration of (+)-TAN-67, at doses of 1 to 10 ng, facilitated the tail-flick response in a dose-dependent manner in mice. In addition, i.t. administration of (+)-TAN-67 (1 to 10 ng) in mice produced a marked pain-like aversive responses. I.t. pretreatment with D-Pro(9)-[spiro-gamma-lactam]-Leu(10)-Trp(11)-physalaemin(1-11) (GR82334, 0.1-1.0 nmol), a potent and selective tachykinin NK(1) receptor antagonist, dose-dependently blocked the reduction of the tail-flick response induced by (+)-TAN-67. Furthermore, (+)-TAN-67-induced facilitation of the tail-flick response was abolished in capsaicin-treated mice. On the other hand, (+)-TAN-67-induced flinching responses were dose-dependently and significantly reduced by i.t. pretreatment with GR82334 (0.1-1.0 nmol). The duration of i.t. (+)-TAN-67-induced flinching responses was significantly reduced in capsaicin-treated mice as compared with naive mice. I.t. administration of nociceptin/orphanin FQ (1-10 nmol) dose-dependently increased the tail-flick latency. I.t. administration of nociceptin/orphanin FQ (0.1-1.0 nmol) significantly and dose-dependently reduced the first-phase nociceptive response, but not the second-phase nociceptive response. I.t. pretreatment with (+)-TAN-67 (0.3-3.0 microg) for 30 min dose-dependently attenuated the antinociception induced by i.t. nociceptin (10 nmol) in the tail-flick test. Furthermore, the antinociceptive effect of nociceptin/orphanin FQ (1 nmol, i.t.) on the first-phase response in the formalin test was dose-dependently attenuated by s.c. pretreatment with (+)-TAN-67 (0.3-3.0 microg). (+)-TAN-67 (0.3-3.0 microg, i.t.), by itself, did not facilitate the tail-flick response or produce apparent behavioral changes. It is possible that (+)-TAN-67 has an antagonistic effect on nociceptin/orphanin FQ-induced antinociception.