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Biomedical subjects

Taketo Yamaguchi

Publications and source records attributed to Taketo Yamaguchi.

At least 37 records · Page 2Linked to original sources

Toxicities and effects of involved-field irradiation with concurrent cisplatin for unresectable carcinoma of the pancreas.

PURPOSE: To evaluate local effects and acute toxicities of involved field irradiation with concurrent cisplatin (CDDP) for unresectable pancreatic carcinoma. MATERIALS AND METHODS: Thirty-three patients with unresectable pancreatic carcinoma were treated with chemoradiotherapy. Sixteen were Stage IVA; 17 were Stage IVB. The total prescribed dose of radiotherapy was 50 Gy/25 fractions or 50.4 Gy/28 fractions, using a three-dimensionally determined involved-field that included only the primary tumor and clinically enlarged lymph nodes. Twelve patients received a daily i.v. infusion of CDDP; 21 patients received a combination of CDDP and 5-fluorouracil either i.v. or through the proper hepatic artery. RESULTS: Twenty-seven (82%) patients completed planned chemoradiotherapy. Nausea was the most frequent complaint. No patient experienced Grade 4 toxicities. More than half achieved pain relief. As for the primary site, only 4 patients (12%) achieved a partial response at 4 weeks; however, 3 additional patients attained >50% tumor reduction thereafter. The most frequent site of disease progression was the liver, and only 3 patients developed local progression alone. No regional lymph nodal progression outside the treatment field was seen. Median survival time and survival at 1 year were 7.1 months and 27%, respectively, for the entire group. Difference in overall survival between patients with and without distant metastases was significant (p = 0.01). CONCLUSIONS: Involved-field irradiation with concurrent daily CDDP was well tolerated without compromising locoregional effects.

Abdominal Pain↗

Oncolytic viral therapy for cervical and ovarian cancer cells by Sindbis virus AR339 strain.

PURPOSE: Recently, the application of replication-competent viruses has been studied as anticancer agents. Sindbis virus (SIN) is an RNA virus that belongs to the Alphavirus genus in the Togaviridae virus family. The AR339 strain of SIN has not been reported to induce any serious disease to humans. EXPERIMENTAL DESIGN: In this study, we evaluated the feasibility of the replication-competent SIN AR339 strain as an agent for cervical and ovarian cancer therapy. RESULTS: SIN infection was able to induce cytopathic effects and apoptosis in two cervical cancer cells (HeLaS3 and C33A) and three ovarian cancer cells (HOC-1, HAC-2, and OMC-3) but not in normal human keratinocytes in vitro. The analysis of cell viability, virus protein synthesis, and viral growth showed the cancer-specific cytotoxicity and virus growth of SIN. In nude mice, i.t. and i.v. inoculation of SIN resulted in significant regression of established cervical tumors implanted at their backs. Histologic studies revealed that systemic treatment with the single injection of SIN induces necrosis within tumors at a remote site. In the metastasis model of ovarian cancer, suppression of ascites formation was observed in nude mice with i.p. SIN treatment. By using an in vivo green fluorescent protein imaging system, we also showed that systemic treatment with SIN targeted tumors specifically. CONCLUSIONS: Our study suggested that SIN AR339 strain has a possibility as a novel agent for human cervical and ovarian cancer therapy.

Animals↗

Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in parkinsonian patients.

Mosapride citrate is a novel selective 5-HT4 receptor agonist. It facilitates acetylcholine release from the enteric cholinergic neurons. In contrast to cisapride, mosapride does not block K(+) channels or D2 dopaminergic receptors. The objective of this study is to perform an open study of mosapride citrate's effects on constipation, a prominent lower gastrointestinal tract disorder in parkinsonian patients. A total of 14 parkinsonian patients (7 with Parkinson's disease, 7 with multiple system atrophy; 10 men, 4 women; mean age, 67 years) with constipation (10 with bowel movement < 3 times/week; 14 with difficulty in defecation) were treated with 15 mg/day of mosapride citrate for 3 months. Pre- and posttreatment objective parameters in colonic transit time (CTT) and rectoanal videomanometry were obtained. Statistical analysis was made by Student's t test. Mosapride was well tolerated by all patients except for 1, who discontinued use of the drug because of epigastric discomfort. None had a worsening of parkinsonism or other adverse events. Thirteen patients reported subjective improvements in bowel frequency (>3 times/week, 13) and difficult defecation (13). Mosapride shortened CTT of the left colon (P < 0.01) and the total colon (P < 0.05). During rectal filling, mosapride lessened the first sensation (P < 0.05) and augmented the amplitude in phasic rectal contraction. During defecation, mosapride augmented the amplitude in rectal contraction (P < 0.05) and lessened the volume of postdefecation residuals. The present study showed for the first time that mosapride citrate augmented lower gastrointestinal tract motility, as shown in CTT and videomanometry, and thereby ameliorated constipation in parkinsonian patients without serious adverse effects.

Aged↗

Long-term results of extracorporeal shockwave lithotripsy and endoscopic therapy for pancreatic stones.

BACKGROUND & AIMS: The aim of this study was to evaluate the short- and long-term results of extracorporeal shockwave lithotripsy (ESWL) and endoscopic therapy for pancreatic stones. METHODS: A total of 117 patients with pancreatic stones underwent ESWL and endoscopic treatment in our institute. Seventy patients who were followed-up for over 3 years after treatment were evaluated retrospectively. RESULTS: Immediate pain relief was achieved in 97% and complete removal of stones was achieved in 56%. During the long-term follow-up evaluation, 49 of 70 patients continued to be asymptomatic. Pain recurred more frequently in patients with incomplete removal than in those with complete removal (P < .05). Twenty-one patients who became symptomatic during the follow-up period underwent additional therapy, and pain relief was attained without surgery in all of them. Both endocrine and exocrine function deteriorated after the long-term follow-up period (P < .05). CONCLUSIONS: ESWL and endoscopic treatment of pancreatic stones proved to be effective for long-term pain relief, especially in patients in whom stones were removed completely at initial therapy.

Adolescent↗

Long-term follow-up of intraductal papillary mucinous neoplasm of the pancreas with ultrasonography.

BACKGROUND & AIMS: Most intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a favorable prognosis. This study was undertaken to clarify the clinical course of IPMNs and to set the criteria for surgical treatment on the basis of long-term follow-up by periodic transabdominal ultrasonography (US). METHODS: Eighty-one patients with IPMN were periodically subjected to US (>3 years); 27 were reviewed retrospectively (12 with benign neoplasms [adenoma, borderline] and 15 with malignant tumors [carcinoma in situ, invasive cancer]) and 54 prospectively. US examination was focused on the main pancreatic duct (MPD) diameter, cyst diameter, and presence or absence and height of the protruding lesion. Differences between the benign and malignant groups were examined to set the criteria for surgical treatment. Follow-up results of prospective patients were investigated. RESULTS: The increase of the MPD or the cyst diameter was significantly greater in the malignant group (P < .01). Maximum increases of the MPD diameter by 2.2 mm/year, the cyst diameter by 11.3 mm/year, and emergence or increase of the height of the protruding lesion by 3.3 mm/year were predominantly observed in the malignant group (accuracy, 90.9%, 81.3%, and 81.5%, respectively). The majority of the prospective patients showed no significant changes of these parameters; however, 2 patients (3.7%) were operated on, with the post-surgery histopathologic diagnosis of cancer. CONCLUSIONS: Periodic imaging follow-up is useful to detect a malignant IPMN. Changes in MPD diameter, cyst diameter, and/or size of the protruding lesion are the practical criteria for selecting surgery.

Aged↗

Usefulness of plasma vascular endothelial growth factor in the diagnosis of pancreatic carcinoma: differential diagnosis, tumor progression, and patient survival.

OBJECTIVES: This study aimed to examine the usefulness of plasma vascular endothelial growth factor (p-VEGF) in patients with pancreatic carcinoma (PC) as a tumor marker for PC in comparison with chronic pancreatitis (CP) and to clarify the relationship between p-VEGF and the clinicopathological features of PC. METHODS: The subjects were 69 patients with PC, 35 with CP, and 26 healthy volunteers (control group). The p-VEGF levels were measured by enzyme-linked immunoassay. RESULTS: p-VEGF levels were significantly higher in the PC group compared with the CP and control groups (P < 0.0001). A cut-off level of 149.5 pg/mL, discriminating between PC and CP, was determined based on a receiver operating characteristic curve. Using this cut-off level, the sensitivity was 60%, specificity was 96%, and accuracy was 73%. Patients with PC with distant metastases exhibited a significantly higher level of p-VEGF compared with those without metastasis (P = 0.0113). Multivariate analysis indicated that a high level of p-VEGF was an independent prognostic factor, and a significant association was observed between p-VEGF and median survival time (P = 0.0092). CONCLUSIONS: p-VEGF proved useful in differentiating between PC and CP, and in patients with PC, a high level of p-VEGF may be a predictor of distant metastases and poor prognosis.

Adult↗

Assessment of portal vein invasion in pancreatic cancer by fusion 3-dimensional ultrasonography.

OBJECTIVE: The purpose of this study was to assess the usefulness of a newly developed imaging technique, fusion 3-dimensional ultrasonography (3DUS) in the diagnosis of portal vein (PV) invasion in patients with pancreatic cancer (PC). METHODS: Fourteen patients with proven PC were examined by fusion 3DUS presented as shaded volume-rendering and multiplanar reconstruction images. The surgical findings were obtained in all patients (12 with resection and 2 without). The findings were compared with those of 2-dimensional ultrasonography (2DUS), contrast-enhanced computed tomography (CT), dynamic CT (DCT), angiography, and surgical findings. Portal vein invasion was assessed by 3 independent radiologists for each modality, and objectivity of the assessment was examined by interobserver variability analysis (kappa value). RESULTS: On the basis of surgical findings, the accuracy rates of 2DUS, fusion 3DUS, DCT, and angiography were 78.6%, 92.9%, 85.3%, and 66.7%, respectively. The kappa values of 2DUS, fusion 3DUS, DCT, and angiography for PV invasion were 0.57, 0.90, 0.63, and 0.49, respectively, being most objective in fusion 3DUS. CONCLUSIONS: Fusion 3DUS is useful for diagnosis of PV invasion of PC.

Adult↗

Treatment of pancreatic stones with extracorporeal shock wave lithotripsy: results of a multicenter survey.

OBJECTIVES: A retrospective multicenter survey was performed to evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) as a treatment of pancreatic stones. METHODS: A survey was sent to 11 institutions belonging to the Japanese Association of Extracorporeal Shock Wave Lithotripsy in Digestive Diseases, and data were collected on 555 patients who underwent ESWL for pancreatic stones between January 1990 and September 2002. The male:female ratio was 5.2:1, and the mean age was 52.5 years. The etiology was alcohol related in 425 patients (76.6%) and idiopathic in 111 patients (20.0%); 204 patients (36.8%) had a single stone and 470 patients (84.7%) were symptomatic. RESULTS: Mean frequency of the procedure was 5.0 times (range, 1-29). Fragmentation of stones was achieved in 513 patients (92.4%), and the complete stone clearance rate after ESWL alone or in combination with interventional endoscopy was 72.6%. Symptom relief was achieved in 428 (91.1%) of 470 patients. Thirty-five patients (6.3%) developed complications, including 30 patients (5.4%) who developed acute pancreatitis. Five hundred four (90.8%) patients were followed for a mean of 44.3 months, during which 122 (22.0%) suffered stone recurrence (mean time to recurrence, 25.1 months). Twenty-two (4.1%) of the 504 patients who were followed required surgery. Pancreatic exocrine function improved in 65 patients (38.0%), was unchanged in 49 patients (28.7%), and progressed in 57 patients (33.3%). Pancreatic endocrine function improved in 44 patients (24.3%), was unchanged in 85 patients (47.0%), and progressed in 52 patients (28.7%). CONCLUSION: ESWL is the treatment of choice for clearing pancreatic stones.

Adolescent↗

Colonic transit time, sphincter EMG, and rectoanal videomanometry in multiple system atrophy.

Both constipation and fecal incontinence are prominent lower gastrointestinal tract (LGIT) dysfunctions that occur frequently in multiple system atrophy (MSA). We investigated the mechanism of constipation and fecal incontinence in MSA. Colonic transit time (CTT), sphincter electromyography (EMG), and rectoanal videomanometry were performed in 15 patients with MSA (10 men, 5 women; mean age, 63.5 years; mean duration of disease, 3 years; decreased bowel frequency [< 3 times a week] in 9; difficulty in expulsion in 11; fecal incontinence in 3) and 10 age-matched healthy control subjects (7 men and 3 women; mean age, 62 years; decreased bowel frequency in 2; mild difficulty in expulsion in 2; fecal incontinence in none). Compared to the control subjects, MSA patients had significantly prolonged CTT in the rectosigmoid segment and total colon. Sphincter EMG showed neurogenic motor unit potentials in none of control subjects but in 93% of MSA patients. At the resting state, MSA patients showed a lower anal squeeze pressure (external sphincter weakness) and a smaller increase in abdominal pressure on coughing. During rectal filling, MSA patients showed smaller amplitude in phasic rectal contraction, which was accompanied by an increase in anal pressure that normally decreased, together with leaking in 3 patients. During defecation, most MSA patients could not defecate completely and had larger postdefecation residuals. MSA patients had weak abdominal strain, smaller rectal contraction on defecation, and larger anal contraction on defecation (paradoxical sphincter contraction on defecation), although these differences were not statistically significant. These findings in MSA patients were similar to those in Parkinson's disease patients in our previous study, except for the sphincter denervation and weakness in MSA. Constipation in MSA most probably results from slow colonic transit, decreased phasic rectal contraction, and weak abdominal strain, and fecal incontinence results from weak anal sphincter due to denervation. The responsible sites for these dysfunctions seem to be both central and peripheral nervous systems that regulate the LGIT.

Aged↗

A sensitive enzymatic assay for the determination of sucrose in serum and urine.

BACKGROUND: Sucrose permeability has been suggested as a simple and non-invasive marker of gastric mucosal damage. We here report on a sensitive enzymatic assay using four sequential enzyme reactions coupled with reduced thio-NADPH. METHODS: Sucrose is phosphorylated by sucrose phosphorylase (EC2.4.1.7). The subsequent reaction in the presence of phosphoglucomutase (EC5.4.2.2) and glucose-1,6-diphosphate forms glucose-6-phosphate. Sucrose of the monad forms the dyad thio-NADPH. The reaction is monitored by changes in absorbance at 405 nm. RESULTS: The lower limit of detection (3SD method) was 2.8 micromol/l for serum and 7.0 micromol/l for urine. The precision of the method was <4.0%, and has sufficient analytical range. CONCLUSIONS: The assay was sensitive enough to monitor serum sucrose concentrations during the sucrose permeability test and an automated assay may be useful in a large number of subjects.

Gastric Mucosa↗

Mitochondrial signal lacking manganese superoxide dismutase failed to prevent cell death by reoxygenation following hypoxia in a human pancreatic cancer cell line, KP4.

One of the major characteristics of tumor is the presence of a hypoxic cell population, which is caused by abnormal distribution of blood vessels. Manganese superoxide dismutase (MnSOD) is a nuclear-encoded mitochondrial enzyme, which scavenges superoxide generated from the electron-transport chain in mitochondria. We examined whether MnSOD protects against hypoxia/reoxygenation (H/R)-induced oxidative stress using a human pancreas carcinoma-originated cell line, KP4. We also examined whether MnSOD is necessarily present in mitochondria to have a function. Normal human MnSOD and MnSOD without a mitochondrial targeting signal were transfected to KP4 cells, and reactive oxygen species, nitric oxide, lipid peroxidation, and apoptosis were examined as a function of time in air following 1 day of hypoxia as a H/R model. Our results showed H/R caused no increase in nitric oxide, but resulted in increases in reactive oxygen species, 4-hydroxy-2-nonenal protein adducts, and apoptosis. Authentic MnSOD protected against these processes and cell death, but MnSOD lacking a mitochondrial targeting signal could not. These results suggest that only when MnSOD is located in mitochondria is it efficient in protecting against cellular injuries by H/R, and they also indicate that mitochondria are primary sites of H/R-induced cellular oxidative injuries.

Aldehydes↗

Spontaneous rupture of pancreatic metastasis from renal cell carcinoma.

We report the case of a 53-year-old female who was admitted for sudden abdominal pain. Her right kidney was resected in 1993 due to renal cell carcinoma. Abdominal computed tomography performed in September 2002, while she was placed under observation, revealed a tumor 40 mm in size that extended from the head to the body of the pancreas. Abdominal ultrasonography on admission indicated retention of ascites, and the aspirated ascites was bloody. Based on this result, spontaneous rupture of a pancreatic tumor was strongly suspected. On abdominal contrast-enhanced computed tomography, multiple tumors were clearly visualized in the pancreas. Angiography revealed high-density tumor in the early arterial phase. The results of endocrinological tests were normal. Accordingly, the patient was diagnosed with multiple pancreatic metastases of renal cell carcinoma, and total pancreatectomy was performed. Histopathologically, the tumor resected was clear cell carcinoma and corresponded to the renal cell carcinoma resected in 1993. This is a rare case of pancreatic metastasis of renal cell carcinoma that resulted in spontaneous rupture 9 years after nephrectomy.

Angiography↗

Diagnostic imaging for pancreatic cancer: computed tomography, magnetic resonance imaging, and positron emission tomography.

Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are sophisticated modalities typically used in the second-line diagnosis following routine clinical practice. Among them, CT is regarded as the standard imaging in diagnosing pancreatic cancer at present in Japan due to its popularity and reasonable reliability in wide-ranging diagnostic ability. However, even with multidetector row CT (MDCT), the demonstration of pancreatic cancer less than 1 cm in size remains nearly impossible. CT staging is considered accurate in one-half to two-thirds of patients, but limitations in the imaging of peripancreatic microinvasion and nodal or hepatic micrometastases still have a tendency to underestimate tumor extension. With recent advancement in imaging techniques, MRI has proven to be equal or superior to other imaging modalities in diagnosing pancreatic cancer. Most of all, it is expected that MRCP will become as effective an instrument as ultra-sonography (US) in the screening of pancreatic cancer. Functional imaging with PET using the glucose analog FDG can be used in the diagnosis of pancreatic cancer, but systemic or local disturbance of glucose metabolism may result in an incorrect diagnosis. The usefulness of PET is now considered in assessing tumor viability, monitoring tumor response to treatment, and detecting distant metastases.

Carcinoma↗

Evaluation of blood flow in pancreatic ductal carcinoma using contrast-enhanced, wide-band Doppler ultrasonography: correlation with tumor characteristics and vascular endothelial growth factor.

BACKGROUND AND AIMS: Tumor vascularization has been attracting attention. However, there have been only a few reports on tumor vascularization in pancreatic ductal carcinoma, especially on vascularization depicted by imaging modalities. We investigated the relationship among wide-band Doppler signals, clinicopathological factors, and vascular endothelial growth factor (VEGF) expression. METHODS: Sixty-nine patients with pancreatic ductal carcinoma were investigated. The vascular signals from carcinoma lesions were assessed by contrast-enhanced, wide-band Doppler ultrasonography (dynamic flow). VEGF expression was quantitated by enzyme immunoassay for 28 patients. Depending on the intensity of the signals, the patients were classified into type A (definite vascular signal) or type B (almost no vascular signal). RESULTS: Type A patients and type B patients accounted for 65% and 35% of patients, respectively. According to multivariate analysis of vascular signal type and clinicopathological factors, liver metastasis occurred significantly more frequently in the type A group. VEGF expression was also significantly higher in the type A group than in the type B group. CONCLUSIONS: Dynamic flow has very high sensitivity for detecting the vascular signals from pancreatic ductal carcinoma. The quantity of vascular signals correlated with tumor characteristics and VEGF.

Carcinoma, Pancreatic Ductal↗

Immunohistochemical localization of type IV collagen alpha chains in the basement membrane of the pancreatic duct in human normal pancreas and pancreatic diseases.

The type IV collagen (Col-IV) consists of 3 alpha chains. Six different alpha chains [alpha1(IV), alpha2(IV), alpha3(IV), alpha4(IV), alpha5(IV), and alpha6(IV)] have been identified, and their combination is considered to be organ specific. We investigated the immunohistochemical localization of alpha (IV) chains in the basement membrane (BM) of the pancreatic duct in human normal pancreas (NP) and pancreatic diseases. Fifty specimens [10 NP, 10 chronic pancreatitis (CP), 10 intraductal papillary mucinous tumor (IPMT), and 20 pancreatic adenocarcinoma (PAC)] were examined. Alpha 1(IV), alpha2(IV), alpha5(IV), and alpha6(IV) were linearly immunostained in NP, CP, and IPMT. In PAC, alpha(IV) and alpha2(IV) were immunostained, but alpha5(IV) and alpha6(IV) were not stained in 30% and 40% of the cases, respectively. In conclusion, immunohistochemically, the Col-IV of human normal pancreatic duct consisted of alpha1(IV), alpha2(IV), alpha5(IV), and alpha6(IV). alpha5(IV) and alpha6(IV) were frequently absent in PAC, and their absence might be related to the invasion of cancer cells.

Adenocarcinoma↗