Takako Sato

Intraoperative radiotherapy for resectable extrahepatic bile duct cancer

PURPOSE Through a retrospective study of intraoperative radiation therapy (IORT) in bile duct cancer, we hope to help clarify its clinical usefulness. METHODS AND MATERIALS Between 1976 and 1996, IORT was carried out in 35 patients with bile duct cancer at the Tokyo Metropolitan Komagome Hospital. Of the 35 patients, resection proved to be curative in 15. Intraoperative irradiation of 15-30 Gy (average 20.1 Gy) was delivered by electron beam in the 5- to 19-MeV energy ranges. Postoperative external-beam radiation therapy (EBRT) was also delivered in 16 patients. The EBRT was fractionated to 2 Gy/day, in principle, and was delivered at 8.8-54 Gy (average 40.4 Gy) by 10-MV X-rays. RESULTS The median survival in our patients was 19 months. The 1-year, 2-year, and 5-year survival rates were 57%, 43%, and 19%, respectively. Statistical analysis identified the following prognostic factors: performance status, curative surgical resection, lymph node metastasis, IORT dosage, and treatment period. Only 1 patient (3%) died within 30 days after surgery, and the incidence of late-onset complications was 21%. CONCLUSION The combination of IORT and EBRT is useful for patients with bile duct cancer who undergo noncurative resection or who have lymph node metastasis.

Organization of cortical processing for facial movements during licking in cats

We proposed that cortical organization for the execution of adequate licking in cats was processed under the control of two kinds of affiliated groups for face and jaw & tongue movements (Hiraba H, Sato T. 2005A. Cerebral control of face, jaw, and tongue movements in awake cats: Changes in regional cerebral blood flow during lateral feeding Somatosens Mot Res 22:307–317). We assumed the cortical organization for face movements from changes in MRN (mastication-related neuron) activities recorded at area M (motor cortex) and orofacial behaviors after the lesion in the facial SI (facial region in the primary somatosensory cortex). Although we showed the relationship between facial SI (area 3b) and area M (area 4δ), the property of area C (area 3a) was not fully described. The aim of this present study is to investigate the functional role of area C (the anterior part of the coronal sulcus) that transfers somatosensory information in facial SI to area M, as shown in a previous paper (Hiraba H. 2004. The function of sensory information from the first somatosensory cortex for facial movements during ingestion in cats Somatosens Mot Res 21:87--97). We examined the properties of MRNs in area C and changes in orofacial behaviors after the area C or area M lesion. MRNs in area C had in common RFs in the lingual, perioral, and mandibular parts, and activity patterns of MRNs showed both post- and pre-movement types. Furthermore, cats with the area C lesion showed similar disorders to cats with the area M lesion, such as the dropping of food from the contralateral mouth, prolongation of the period of ingestion and mastication, and so on. From these results, we believe firmly the organization of unilateral cortical processing in facial SI, area C, and area M for face movements during licking.

Cortical control for mastication in cats: changes in masticatory movements following lesions in the masticatory cortex.

In a previous paper (Hiraba and Sato ) we reported that an accurate mastication might be executed by the cortical processing in bilateral masticatory area (MA)and motor cortices. The aim of this study was to determine if cats with lesion of either unilateral or bilateral MA showed changes in mastication. After exploring mechanoreceptive fields and motor effects of mastication-related neurons (MRNs) in MA using the single unit recording and intracortical microstimulation methods, we made various lesions in MAs with injections of kainic acid (0.1%, 2.0 µl). Since the MA was divided into facial (F) and intraoral (I) projection areas as reported in the previous paper, cats with the unilateral lesion in F or I, and with the bilateral lesion in F & F, I & I or F & I (F on one side and I on other side) were prepared. Cats with unilateral lesion in F or I and with bilateral lesion in F & I showed no changes in mastication except for prolongation of the food intake and masticatory periods. Cats with bilateral lesion into F & F, or I & I showed wider jaw-opening during mastication. Particularly, the latter group showed enormous jaw-opening, delay in the start of mastication and difficulty in manipulating food on the tongue. In all cats with lesions of each type, masticatory and swallowing rhythms remained normal. These findings suggest that accurate mastication is executed by the close integration between F & F and I & I of the bilateral MA.

Cortical control of mastication in the cat: properties of mastication-related neurons in motor and masticatory cortices.

The aim of this study is to examine mastication-specific activity of orofacial neurons in the motor and masticatory cortices of the awake cat. We examine properties of mastication-related neurons (MRNs) in masticatory (MA, the rostral region of the orbital gyrus) and motor (area P, the lateral wall of the presylvian sulcus) cortical areas that are related to mastication of cats. MRNs in MA and area P had in common mechanoreceptive fields (RFs) in perioral, mandibular and lingual regions, and many MRNs had bilateral RFs in the tongue and mandibular regions. Facial RF size was the largest in area P. Eleven percent of MRN recording sites in MA, and 43% in area P evoked various motor effects with the use of intracortical microstimulation (ICMS). MRNs of the pre-movement type showing activities prior to mastication, or masticatory or lingual EMG, were 14% in MA and 45% in area P. Based on wheat germ agglutinin–horseradish peroxidase (WGA-HRP) injection into area P and MA, cortico-cortical connections were examined. After the unilateral area P injection, were reciprocal connections between the contralateral area P and bilateral MA were demonstrated. After the unilateral MA injection, there were reciprocal connections between the contralateral MA, bilateral area P and bilateral orofacial SI (the orofacial region of the first somatosensory area). These findings suggest that accurate masticatory movements may be executed by the cortical processing in MA and area P.

Cortical control of mastication in cats. 2. Deficits of masticatory movements following a lesion in the motor cortex

Our previous study suggested that area P in the lateral wall of the presylvian sulcus and MA (masticatory cortex) in the rostral part of the orbital gyrus play an important role in execution of mastication. The aim of this present study is to examine if changes in orofacial behaviors and masticatory movements occur in cats with lesions of area P. First, we explored the locations in area P through the use of single unit recording and ICMS (intracortical microstimulation). Since mastication related neurons (MRNs) with the mechanical receptive field (RF) in facial or intraoral region were intermingled in area P, we performed either a partial or entire lesion in area P by injections of 2 microl or 4 microl of 0.1% kainic acid. Cats with the entire lesion in area P showed a decrease of food intake rates associated with abnormal tongue protrusion and wide jaw-opening, fluctuation of masticatory start, and prolongation of masticatory and food intake periods. Abnormal movements of tongue and jaw did not recover, although their prolongation and fluctuation returned to normal levels in one month. On the other hand, all deficits evoked by cats with the partial lesion recovered in about one month. In cats with the partial and entire lesions, masticatory rhythm remained normal. These findings suggest that area P may regulate accurate and suitable tongue and jaw movements during mastication depending on cortical processing.

Cerebral control of face, jaw, and tongue movements in awake cats : Changes in regional cerebral blood flow during lateral feeding

Mastication is achieved by cooperation among facial, masticatory, and lingual muscles. However, cortical control in cats for the masticatory performance is processed by two systems: facial movement processed by facial SI (the first somatosensory cortex), area C, and area M (motor areas), and jaw and tongue movements performed by intraoral SI, masticatory area, and area P (motor area). In particular, outputs from area P organized in the corticobulbar tract are projected bilaterally in the brainstem. In this present study, the aim is to explore changes in the regional cerebral blood flow (rCBF) in the facial SI, area M, and area P during trained lateral feeding (licking or chewing from the right or left side) of milk, fish paste, and small dry fish. The rCBF in area M showed contralateral dominance, and rCBF in area P during chewing or licking from the right or left side was almost the same value. Furthermore, activities of genioglossus and masseter muscles in the left side showed almost the same values during licking of milk and of fish paste, and chewing of small dry fish during lateral feeding. These findings suggest that the cortical process for facial, jaw, and tongue movements may be regulated by the contralateral dominance of area M and the bilateral one of area P.

Radiotherapy to pulmonary metastases of a malignant phyllodes tumor of the breast

A bulky right breast tumor (15 × 15 cm) was discovered in a 54-year-old woman, and a simple mastectomy was performed, followed by 50 Gy of postoperative radiotherapy. Histologically, the tumor was malignant phyllodes tumor of the breast. Nine months after the mastectomy, multiple pulmonary metastases were detected and three lesions were treated with radiotherapy of 60 Gy/30 fractions for 43–54 days. Two lesions (16 × 12 mm and 18 × 16 mm) showed a partial response and no progression 2–4 months after the radiotherapy. The other lesion (22 × 18 mm) showed a partial response but progressed again 3 months later. She died of respiratory failure 18 months after the mastectomy. She also had muscle metastasis, but there were no locoregional recurrences. The malignant phyllodes tumor in this patient, showed a partial response to radiotherapy. Radiotherapy is considered useful for local control or symptomatic treatment of malignant phyllodes tumor.

Facial Vibrotactile Stimulation Activates the Parasympathetic Nervous System: Study of Salivary Secretion, Heart Rate, Pupillary Reflex, and Functional Near-Infrared Spectroscopy Activity

We previously found that the greatest salivation response in healthy human subjects is produced by facial vibrotactile stimulation of 89 Hz frequency with 1.9 μm amplitude (89 Hz-S), as reported by Hiraba et al. (2012, 20011, and 2008). We assessed relationships between the blood flow to brain via functional near-infrared spectroscopy (fNIRS) in the frontal cortex and autonomic parameters. We used the heart rate (HRV: heart rate variability analysis in RR intervals), pupil reflex, and salivation as parameters, but the interrelation between each parameter and fNIRS measures remains unknown. We were to investigate the relationship in response to established paradigms using simultaneously each parameter-fNIRS recording in healthy human subjects. Analysis of fNIRS was examined by a comparison of various values between before and after various stimuli (89 Hz-S, 114 Hz-S, listen to classic music, and “Ahh” vocalization). We confirmed that vibrotactile stimulation (89 Hz) of the parotid glands led to the greatest salivation, greatest increase in heart rate variability, and the most constricted pupils. Furthermore, there were almost no detectable differences between fNIRS during 89 Hz-S and fNIRS during listening to classical music of fans. Thus, vibrotactile stimulation of 89 Hz seems to evoke parasympathetic activity.

Optimal Vibrotactile Stimulation Activates the Parasympathetic Nervous System

We currently live in an environment that has become more and more stressful. Escaping from the stress in society through various activities (e.g., acupuncture, massage, listening to classic music or natural sounds, etc.) is important for our mental health. We previously re‐ ported that optimal facial vibrotactile stimulation (i.e., 89 Hz frequency and 1.9 μm ampli‐ tude [89 Hz-S]) might activate the parasympathetic nervous system (Hiraba et al. 2008, 2011). Specifically, we showed that 89 Hz-S stimulation of the face led to increased saliva‐ tion and a feeling of mental well-being through parasympathetic activity based on function‐ al near-infrared spectroscopy (fNIRS) oxyhaemoglobin (oxyHb) activity. Namely, brain blood flow (BBF) oxyHb in the frontal cortex was near zero (Hiraba et al. 2011). We investi‐ gated adaptation to the continuous use of vibrotactile stimuli for 4 or 5 days in the same subjects to determine whether this resulted in decreased salivation (Despopoulos and Silber‐ nagel, 2003; Principles of Neural Science, 2000a). Then, we compared resting and stimulated salivation and investigated the most effective frequency for increasing salivary secretion. In‐ creased salivation in normal subjects was defined as a difference between resting and stimu‐ lated salivation (Hiraba et al. 2011).

Changes in Brain Blood Flow on Frontal Cortex Depending on Facial Vibrotactile Stimuli

We provide patients who have problems with reduced salivation (hyposalivation) with artificial saliva treatment, humectants, and salivary gland massage (Ueda et al. 2005). However, treatment with artificial saliva and humectants is symptomatic, and although salivary gland massage can reinvigorate weak glands, to do so is difficult for people with disabilities and has varying effects, depending on operator skill. Thus, we have focused on increasing salivation through the use of vibrotactile stimulation, as reported by Hiraba et al. (2008). Before using this apparatus on patients, it was necessary to first estimate the effect on normal subjects. The biggest challenge with continuous use of stimulation is an adaptive effect. In particular, we were interested in determining whether the effect was continuous without attenuation, when patients continue using the apparatus every day (Despopoulos and Silbernagel, 2003). We investigated adaptation to the continuous use of vibrotactile stimuli for 4 or 5 days in the same subjects to determine whether this resulted in a decrease in salivation (Despopoulos and Silbernagel, 2003; Principles of Neural Science. 2000a). Before this experiment was performed, it was necessary to compare resting and stimulating salivary secretion and to investigate the most effective frequency for increasing salivary secretion. We examined the amount of salivation during vibrotactile stimuli with a single motor (1.9 μm amplitude) on the bilateral masseter muscle belly (on the parotid glands), using a dental cotton roll positioned at the opening of the secretory duct for 3 min. Furthermore, we examined the amount of salivation during vibrotactile stimuli with single and double motors (1.9 μm and 3.5 μm amplitudes) on the bilateral submandibular angles (on the submandibular glands). Then, we compared resting and stimulating salivation and investigated the most effective frequency for increasing salivary secretion. The effect of increased salivation in normal subjects was determined as the difference between resting and stimulating salivation. We defined a 5-min interval as the recovery time between resting and stimulating salivation from a preliminary study. First, we examined the most effective frequency for salivation of