Dopamine in Auditory Nuclei and Lemniscal Projections is Poised to Influence Acoustic Integration in the Inferior Colliculus.

Dopamine (DA) modulates the activity of nuclei within the ascending and descending auditory pathway. Previous studies have identified neurons and fibers in the inferior colliculus (IC) which are positively labeled for tyrosine hydroxylase (TH), a key enzyme in the synthesis of dopamine. However, the origins of the tyrosine hydroxylase positive projections to the inferior colliculus have not been fully explored. The lateral lemniscus (LL) provides a robust inhibitory projection to the inferior colliculus and plays a role in the temporal processing of sound. In the present study, immunoreactivity for tyrosine hydroxylase was examined in animals with and without 6-hydroxydopamine (6-OHDA) lesions. Lesioning, with 6-OHDA placed in the inferior colliculus, led to a significant reduction in tyrosine hydroxylase immuno-positive labeling in the lateral lemniscus and inferior colliculus. Immunolabeling for dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT), enzymes responsible for the synthesis of norepinephrine (NE) and epinephrine (E), respectively, were evaluated. Very little immunoreactivity for DBH and no immunoreactivity for PNMT was found within the cell bodies of the dorsal, intermediate, or ventral nucleus of the lateral lemniscus. The results indicate that catecholaminergic neurons of the lateral lemniscus are likely dopaminergic and not noradrenergic or adrenergic. Next, high-pressure liquid chromatography (HPLC) analysis was used to confirm that dopamine is present in the inferior colliculus and nuclei that send projections to the inferior colliculus, including the cochlear nucleus (CN), superior olivary complex (SOC), lateral lemniscus, and auditory cortex (AC). Finally, fluorogold, a retrograde tracer, was injected into the inferior colliculus of adult rats. Each subdivision of the lateral lemniscus contained fluorogold within the somata, with the dorsal nucleus of the lateral lemniscus showing the most robust projections to the inferior colliculus. Fluorogold-tyrosine hydroxylase colocalization within the lateral lemniscus was assessed. The dorsal and intermediate nuclei neurons exhibiting similar degrees of colocalization, while neurons of the ventral nucleus had significantly fewer colocalized fluorogold-tyrosine hydroxylase labeled neurons. These results suggest that several auditory nuclei that project to the inferior colliculus contain dopamine, dopaminergic neurons in the lateral lemniscus project to the inferior colliculus and that dopaminergic neurotransmission is poised to play a pivotal role in the function of the inferior colliculus.

Dopamine in the auditory brainstem and midbrain: co-localization with amino acid neurotransmitters and gene expression following cochlear trauma.

Dopamine (DA) modulates the effects of amino acid neurotransmitters (AANs), including GABA and glutamate, in motor, visual, olfactory, and reward systems (Hnasko et al., 2010; Stuber et al., 2010; Hnasko and Edwards, 2012). The results suggest that DA may play a similar modulatory role in the auditory pathways. Previous studies have shown that deafness results in decreased GABA release, changes in excitatory neurotransmitter levels, and increased spontaneous neuronal activity within brainstem regions related to auditory function. Modulation of the expression and localization of tyrosine hydroxylase (TH; the rate limiting enzyme in the production of DA) in the IC following cochlear trauma has been previously reported (Tong et al., 2005). In the current study the possibility of co-localization of TH with AANs was examined. Changes in the gene expression of TH were compared with changes in the gene expression of markers for AANs in the cochlear nucleus (CN) and inferior colliculus (IC) to determine whether those deafness related changes occur concurrently. The results indicate that bilateral cochlear ablation significantly reduced TH gene expression in the CN after 2 months while in the IC the reduction in TH was observed at both 3 days and 2 months following ablation. Furthermore, in the CN, glycine transporter 2 (GLYT2) and the GABA transporter (GABAtp) were also significantly reduced only after 2 months. However, in the IC, DA receptor 1 (DRDA1), vesicular glutamate transporters 2 and 3 (VGLUT2, VGLUT3), GABAtp and GAD67 were reduced in expression both at the 3 days and 2 months time points. A close relationship between the distribution of TH and several of the AANs was determined in both the CN and the IC. In addition, GLYT2 and VGLUT3 each co-localized with TH within IC somata and dendrites. Therefore, the results of the current study suggest that DA is spatially well positioned to influence the effects of AANs on auditory neurons.

Downregulation of N-methyl-D-aspartate receptor ζ1 subunit (GluN1) gene in inferior colliculus with aging.

Presbycusis is the impairment of auditory function associated with aging, which stems from peripheral cochlear lesions and degeneration of the central auditory process. The effect of age-induced peripheral hearing loss on the central auditory process is not fully understood. C57Bl/6 (C57) mice present accelerated peripheral hearing loss, which is well developed by middle-age and mimics the human presbycusis pattern. The aim of this study was to elucidate the molecular effects of peripheral hearing loss in the inferior colliculus (IC) with age between young and middle-aged C57 mice using cDNA microarray. Glutamate receptor ionotropic NMDA ζ1 (GluN1) exhibited the greatest decrease in the middle-aged group as determined using cDNA microarray and by further assessment using real-time PCR (qPCR). Histological assessment with in situ hybridization of GluN1 showed significantly decreased expression in all IC subdivisions of the middle-aged group. GluN1 is a receptor for excitatory neurotransmission, and significant downregulation of this gene may be subsequent to the decline of afferent input from the cochlea in aging C57 mice. Consequently, using the combination of microarray, qPCR, and in situ hybridization, we showed that the decline of GluN1 in the IC of aging animals might have a key role in the pathogenesis of presbycusis.

[Two case reports-a control of the bleeding from advanced gastric cancer, unable to undergo resection, but was possible by transcatheter arterial embolization (TAE)].

CASE 1: A 61-year-old man having advanced gastric cancer was presented with massive hematemesis. We could not control bleeding by gastrointestinal endoscopic hemostatic therapy, so we performed a transcatheter arterial embolization (TAE). We performed embolization on the left gastric artery. CASE 2: A 58-year-old man having advanced gastric cancer was presented with hematemesis. We could not control bleeding by gastrointestinal endoscopic procedure, so we conducted TAE. We performed embolization on the left gastric artery and right gastric artery. In both cases, hemostasis was achieved by TAE, and effectively controlled the bleeding from advanced gastric cancer.

[A case of intrahepatic recurrence of intrahepatic cholangiocarcinoma treated with repeated hepatectomy].

A 60-year-old man with intrahepatic cholangiocarcinoma (ICC) underwent a left hepatectomy. Following the procedure, S-1 was administered during the period of five months. About two years after the hepatectomy, the patient underwent a hepatic resection again for remunant hepatic recurrences of ICC. Aggressive surgical resection may be the only method to assure a good outcome. An indication of resection for the hepatic recurrence of ICC will be examined in the future.

[A radical resection of non-small cell lung cancer invading chest wall with ipsilateral axillary lymph node metastases].

A 41-year-old man who had non-small cell lung cancer invading his right 3rd, 4th and 5th ribs with hilum lymph node swelling(cT3N1M0, cStage III A), received chemoradiation therapy, cisplatin(CDDP)/docetaxel, and 2 Gy/Fr of irradiation prior to surgery. But the therapy was discontinued due to interstitial pneumonitis on day 24, during 28 Gy of radiation. At that time, a PET-CT scan revealed the accumulation of FDG in the primary tumor, hilar lymph node, and one of the ipsilateral axillar lymph nodes, in which cancer cell presence was proven by aspiration needle cytology. We organized a radical operation even though the node status was classified to cStage IV, because ipsilateral axillary lymph nodes may be regarded as regional nodes for tumors invading the chest wall. Right upper lobectomy and chest wall resection were performed, and the ipsilateral hilar, mediastinal, and axillary lymphnode were dissected. Pathological findings showed no active cancer cell in the primary lesion and hilar lymph nodes(Ef. 3), but obvious metastasis in one of the axillary lymph nodes(pT0N0M1b, pStage IV). The patient received adjuvant chemotherapy(CDDP/vinorelbine), and is alive and tumor-free 10months after the resection.

[Long-term control of sacral metastasis from rectal cancer with S-1 + radiation treatment (RT) and mFOLFOX6 combination therapy--a case report].

Combined chemotherapy including 5-FU plus radiation treatment resulted in a synergistic effect has been reported. S-1 enhances a radiation response of colon cancer cell line xenografts. Also the effectiveness of S-1 + radiation therapy has been reported. A 66-year-old man underwent a low anterior resection for lower rectal cancer. Adjuvant chemotherapy was not performed due to Stage II rectal cancer. Twenty months after the operation, solitary sacral bone metastasis was found during the postoperative work-up. S-1 (120 mg/day) combined with radiotherapy was performed on days 1-14 and 21-35. Radiation (3 Gy) was administered a total of 45 Gy on days 1-5, 7-12 and 35-40. Moreover, the reduction was judged as complete response after 11 courses of mFOLFOX 6. There has been no sign of recurrence for 44 months. It suggested that local control therapy (S-1 + radiation) plus systemic chemotherapy (mFOLFOX6) was one of the promising effective therapies for single sacral bone metastasis of rectal cancer.

[Evaluation of systemic chemotherapy for unresectable gallbladder carcinoma].

We analyzed a treatment outcome and the effect of systemic chemotherapy for patient with unresectable gallbladder carcinoma. Sixteen patients were investigated. Gemcitabine (GEM) was administrated for fifteen patients as the first-line chemotherapy. S-1 was administrated for ten patients as the second-line chemotherapy. The response rate and tumor control rate of the first-line GEM were 14.3% and 78.6%, respectively. The median progression free time of the first-line GEM was 6.0 months. The response rate and tumor control rate of the second-line S-1 were respectively 20.0% and 30.0%. The median progression free time of the second-line S-1 was 1.8 months. The median survival time of all cases was 14.9 months. The outcome of systemic chemotherapy for patients with unresectable gallbladder carcinoma in our hospital was feasible compared with past reports.

[A case report--transarterial embolization for advanced gallbladder carcinoma with hepatic metastasis].

A 75-year-old female presented with appetite and weight loss and epigastralgia. CT revealed a primary gallbladder carcinoma Stage IVb with multiple hepatic metastases. Gastrofiberscopy revealed an invasion to duodenal and bleeding from the tumor. For her poor performance status, it seems to be too difficult to undergo a general chemotherapy. So after gastrojejunostomy, transarterial embolization (TAE) was performed. She underwent 2 times TAE. There was a notable reduction in tumor size. But pulmonary metastases were found in bilateral lung. She died after 8 months. TAE may be useful for advanced gallbladder carcinoma with tumor vascularity.

[Radiofrequency ablation combined with transcatheter arterial chemoembolization for the local recurrent tumor after resection of the adrenal metastasis from hepatocellular carcinoma--a case report].

We report a case of local recurrent tumor after a resection of right adrenal metastasis from hepatocellular carcinoma successfully treated with radiofrequency ablation combined with transcatheter arterial chemoembolization. The case is a man in his 80s who had a curative surgical resection and microwave coagulation therapy (MCT) for multiple hepatocellular carcinomas in February 2003. The lesions were judged to be T4, N0, M0 and Stage IV,then, he was treated as an outpatient on a regular schedule. In July 2003, a right adrenal tumor 2 cm in diameter was detected by computed tomography (CT), but the value of the adrenocortical hormones were normal on blood examination, and he was observed at regular intervals. In February 2005, the adrenal lesion enlarged to 5 cm in diameter and the value of PIVKA-II became high on blood examination, so April 2005, a surgical resection was performed, and it was diagnosed as the metastasis from HCC. In July 2008, the recurrent tumor 3 cm in diameter was observed in the right retroperitoneum. It was considered inoperable because of the past operation, and transcatheter arterial chemoembolization of an inferior adrenal artery and a fine branch through a right sub-phrenic artery was performed for the recurrent tumor, and one week after the embolization, radiofrequency ablation was treated by CT fluoroscopy guidance. Ten months after the tumor embolization combined with radiofrequency ablation, there were no local and distant recurrences observed by CT examination. Transcatheter arterial embolization combined with radiofrequency ablation is considered as a feasible and effective method for not only HCC but also for a local recurrent tumor after resection of the adrenal metastasis from hepatocellular carcinoma.

[A case report of combined hepatocellular-cholangiocarcinoma whose lymph node recurrence effectively treated with UFT].

Primary liver cancer with lymph node metastasis was recognized as poor prognosis. We herein report a case of post operative lymph node recurrence treated with UFT. A 74-year-old man with a huge mass lesion in the right liver with para Aortic lymph node metastasis admitted our hospital in April 2007. Extended right lobe hepatectomy and lymph node dissection were performed in May. A histological examination of the resected specimen showed a combined hepatocellular-cholangiocarcinoma with three lymph node metastasis. Computed tomography(CT)revealed intra hepatic metastasis (S3) and right adrenal grand metastasis 5 months after surgery. Transarterial embolization (TAE) and right adrenalectomy were performed for each metastasis. CT revealed a lymph node metastasis at the right side of infra vena cava 1 year after surgery. He was treated by oral administration of UFT (200 mg/day). The AFP and PIVKA-II value gradually decreased after administration of UFT. The size of lymph node metastasis became small confirmed by CT. But the AFP and PIVKA-II value increased 1 year and 7 months after surgery. TAE was performed against lymph node metastasis 1 year and 9 months after surgery. This case suggests UFT is useful for suppressing the growth of the lymph node metastasis.

[A case of bile peritonitis caused by jejunal perforation after radiofrequency ablation for the multiple liver metastases from cholangiocarcinoma successfully treated with various interventional radiological procedures after pancreatoduodenectomy].

The case is a man in his 50s who had a curative surgical resection for cholangiocarcinoma in August 2006. The lesion was judged to be T3, N1, H0, P0, M0 and Stage III, and then he received various treatments including thermotherapy, CD3-activated T lymphocyte therapy. Then from June 2007, he was treated for multiple liver metastases by GEM, radiofrequency ablation (RFA), stereotactic radiotherapy, S-1, dendritic cell therapy. But there were multiple liver metastases whose maximum size was 17 mm in diameter and he was introduced to our hospital. In September 2008, ultrasonography and CT fluoroscopy guided RFA was operated on him for the liver tumors with a safety margin. But 2 hours after the ablation, he complained of epigastralgia. CT examination revealed a bile peritonitis caused by perforation of the jejunum which has been anastomosed to the pancreas, and was adjacent to the avascular area caused by RFA in segment 4 of the liver. We treated him by various interventional procedures including percutaneous drainage for bile leakage, pancreatic fistula, abscess in peritoneal cavity, and biloma in segment 3. Fifty days after the ablation, T-tube, with which pancreatic fluid and bile was induced from the cecal portion of the anastomosed jejunum to the anal side slipping through the perforated point, was successfully inserted through right flank, and resulted in complete recovery from a major technical complication of the bile peritonitis.

[Complete response of advanced rectal cancer with combined therapy of S-1 + chemo-radiation plus FOLFIRI--a case report].

A 64-year-old man was admitted to general practitioner because of dyschezia. He was diagnosed with lower rectal cancer by colonoscopy and referred to our hospital for therapy. At first, in spite of multiple liver metastases, we tried a resection of primary lesion in order to control of breeding, dyschezia and pain. However, we had to give up the resection, so we made sigmoid colostomy only. One month after the operation, a combination chemo-radiotherapy using S-1 was performed for controlling of local symptom. S-1 (120 mg/day) was administered on days 1-14, and 21-35. Radiation (2 Gy) was administered on days 1-5, 7-12, 14-19, 21-26, 28-33, and 35-40, a total of 60 Gy. One month after this therapy, the tumor was remarkably reduced and the reduction was judged as partial response. Moreover after 6 courses of FOLFIRI, the reduction was judged as complete response. Local control therapy (S-1+chemo-radiation) plus systemic therapy (FOLFIRI) is one of the promising effective therapies for advanced rectal cancer.

Early acquisition of esophageal phonation following tracheoesophageal phonation.

CONCLUSIONS: Tracheoesophageal phonation appears to participate in early acquisition of esophageal phonation, which remains the preferred method of voice restoration among patients. Further studies into factors predicting and mechanisms underlying acquisition of esophageal phonation among alaryngeal patients may provide information facilitating superior quality of life. OBJECTIVE: The aim of this study was to examine early acquisition of esophageal phonation following tracheoesophageal phonation, and underlying mechanisms and preferred phonatory methods for alaryngeal patients who master both tracheoesophageal and esophageal phonation. PATIENTS AND METHODS: Subjects comprised 44 alaryngeal patients and were divided into three groups: group A (n=13), esophageal phonation alone; group B (n=21), tracheoesophageal phonation alone; and group C (n=10), patients who acquired esophageal phonation after learning tracheoesophageal phonation. RESULTS: The results indicated that acquisition of tracheoesophageal phonation significantly accelerated acquisition of esophageal phonation to 59.3 days from 184.6 days. Patients in group C stopped tracheoesophageal phonation and predominantly used esophageal phonation. No factors predicting acquisition of esophageal phonation were identified among patients who had mastered tracheoesophageal phonation, including age at time of surgery, irradiation, neck dissection, acquisition time of tracheoesophageal phonation, and maximum phonation time of tracheoesophageal phonation. No evidence of air leakage through the shunt during esophageal phonation was noted in group C.

[A case of pseudo aneurysm of common hepatic artery related to hepatic arterial infusion chemotherapy].

A 87-year-old male underwent the extended hepatic left lobectomy and the partial hepatectomy (S7, S8) for liver hepatic metastasis from the rectal cancer in March 2003. The reserver was implanted by the GDA-coil method from the right femoral artery, and WHF was enforced 10 times. Epigastric and back pain appeared from January 2004. The pain became strong gradually. MRI and CT scan were examined after hospitalization. These imaging tests showed the pseudo aneurysm of common hepatic artery. Therefore, an emergency angiography was performed, and pseudo aneurysm of the common hepatic artery was embolized with 36 metallic coils. After the embolization, the pain had disappeared suddenly. The patient was discharged the 7th day after embolization. Hepatic arterial infusion chemotherapy is considered safe with respect to blood and non blood toxicity, which was compared with systemic chemotherapy. However, there were also complications like this case, and caution is required.

Preoperative iron supplementation and intraoperative transfusion during colorectal cancer surgery.

PURPOSE: To investigative whether giving an iron preparation to anemic patients before colorectal cancer surgery improves their anemia and reduces the need for intraoperative blood transfusion. METHODS: Among 569 patients who underwent colorectal cancer surgery between 1998 and 2003, we studied 32 anemic patients who received iron supplementation for at least 2 weeks preoperatively (group A) and 84 anemic patients who did not (group B). Anemia was defined as a hemoglobin (Hb) level at first presentation of

Preoperative sonographic evaluation is a useful method of detecting contralateral patent processus vaginalis in pediatric patients with unilateral inguinal hernia.

BACKGROUND/PURPOSE: To analyze the value of ultrasound scan (US) in the preoperative identification of a contralateral patent processus vaginalis (CPPV), the authors investigated the presence of CPPV by US in children with clinically diagnosed unilateral inguinal hernias. METHODS: Three hundred forty-eight patients (168 boys and 180 girls) with unilateral inguinal hernia underwent US examination using a 7.5-MHz linear transducer. If a CPPV was visible as a hydrocele owing to the inflow of physiologic ascites into a processus vaginalis on straining, then US scanning was performed while the patient was at rest and while inducing straining by standing or crying. A groin with a hydrocele in the inguinal canal on straining was diagnosed as a CPPV and was explored bilaterally through surgery. The US findings were compared with surgical results. RESULTS: In 348 patients, 78 cases (22.4%) were diagnosed by US as patients with a CPPV; these patients underwent bilateral surgery. Seventy-four of 78 cases (94.9%) were confirmed surgically as patients with CPPV. CONCLUSIONS: A CPPV was detected correctly by US in 74 of 348 patients (21.3%) with clinically diagnosed unilateral inguinal hernias. US is a noninvasive and accurate method for evaluating the presence of a CPPV.

[Microwave coagulation therapy for liver metastases from colorectal cancer].

Hepatic resection has gained acceptance as the most effective therapy for liver metastases from colorectal cancer. Microwave coagulation therapy (MCT) and radiofrequency ablation as well as resection are also reported as effective therapies. We analyzed the prognosis of 52 patients with liver metastases from colorectal cancer treated with MCT as the first radical therapy. A total of 4 percutaneous MCT's (3 cases with interruption of hepatic blood flow), 23 MCT's with laparotomy, and 25 with hepatic resection + MCT with laparotomy were performed. Thirty-three MCT's performed as a second therapy for recurrence in the liver were also analyzed. Clinical risk scoring as reported by Fong, et al was used in our cases. The indication for percutaneous MCT with interruption of hepatic blood flow is solitary tumor less than 20 mm in diameter. The 5-year survival rate for the 4 percutaneous MCT's, 23 MCT's with laparotomy, and 25 hepatic resection + MCT's with laparotomy and 68 hepatic resections were 20, 24 and 24%, respectively. No significant difference was found among them. The 5-year survival rate for the 17 MCT's and 12 hepatic resections with recurrence in the liver were 20% and 24%, respectively. There was no significant difference found between them. The 5-year survival rate for the 28 CRS3 was 17%, almost equal to the rate, 20%, reported by Fong, et al for hepatic resections only. MCT is effective therapy for liver metastases from colorectal cancer, recurrence in the liver, and hepatic resections.

[Outcomes of patients undergoing microwave coagulation therapy for liver metastases from colorectal cancer].

To evaluate the efficacy of microwave coagulation therapy (MCT) for liver metastases from colorectal cancer, we analyzed the survival and the disease-free survival rate. From 1990 to 2001, 18 patients with liver metastases measuring < or = 3 cm in diameter and number of metastases < or = 3 were treated with MCT. The 3- and 5-year survival rates were 62% and 18%, respectively. These results are almost equal to those for liver resection. The disease-free survival rate was 86% and 52%, respectively. Local recurrence has not been observed, which puts the disease-free interval over 24 months. MCT can be considered an effective therapy for liver metastases from colorectal cancer.

[Comparison of percutaneous microwave coagulation area under interruption of hepatic arterial blood flow with that under hepatic arterial and venous blood flow for hepatocellular carcinoma].

The study subjects were 49 patients with hepatocellular carcinoma. Twenty-nine patients underwent hepatic arterial blood flow block via thrombosis of the cancer-bearing area with a gelatin sponge, while the other 20 patients underwent a combination of hepatic arterial block and partial blood flow block of the portal vein with a hepatic venous balloon. Percutaneous microwave coagulation therapy (PMCT) was performed on these patients according to the type of hepatic blood flow block, and the diameters of the coagulation areas in the two groups were compared using CT images taken under portal venography. The 29 patients who underwent hepatic arterial block (A-PMCT) had a mean tumor diameter of 19.2 +/- 8 mm, while the 20 patients who underwent hepatic arterial and hepatic venous block (AV-PMCT) had a mean tumor diameter of 25.3 +/- 8.3 mm. PMCT was performed at 60 W. The mean coagulation time and the mean coagulation diameter were 4.2 +/- 1.1 min and 36.3 +/- 12.3 mm, respectively, for the A-PMCT group and 5.5 +/- 1.8 min and 43.9 +/- 9.8 mm, respectively, for the AV-PMCT group. A comparison of the coagulation diameters indicated that the AV-PMCT group had a significantly greater coagulation area than the A-PMCT group (p < 0.05).