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Biomedical subjects

Akimasa Nakao

Publications and source records attributed to Akimasa Nakao.

At least 19 recordsLinked to original sources

Parameter predicting the recurrence of adhesive small bowel obstruction in patients managed with a long tube.

INTRODUCTION: Some of our patients showed a recurrence of adhesive small bowel obstruction (ASBO) with nonoperative management. The aim of this study was to evaluate the parameters predicting the recurrence of ASBO in patients managed with a long tube. METHODS: Of 234 patients with ASBO admitted from April 1998 to September 2002, a total of 91 who recovered with nonoperative management after long tube placement were enrolled in this retrospective clinical study. We divided them into two groups for follow-up: the recurrence group and the no-recurrence group. We compared baseline characteristics, the number of previous ASBO admissions, the number of abdominal operations, the interval from the onset of symptoms to long-tube insertion, the duration of long-tube placement, the type of the contrasted intestine through the long tube, the location of the long-tube tip, and the drainage volume through the long tube between the two groups. We then examined the cumulative recurrence rate. RESULTS: A significant difference was found in the number of previous ASBO admissions, the duration of long-tube placement (77 hours vs. 43 hours), the contrasted intestine through the long tube, and the location of the long-tube tip. By multivariate analysis, the duration of long-tube placement was an independent parameter predicting the recurrence of ASBO. CONCLUSIONS: These results suggest that the duration of long-tube placement might serve as a parameter for predicting recurrence of ASBO in patients managed with a long tube.

Adolescent↗

Relation between human decay-accelerating factor (hDAF) expression in pig cells and inhibition of human serum anti-pig cytotoxicity: value of highly expressed hDAF for xenotransplantation.

BACKGROUND: Although the successful production of alpha1,3-galactosyltransferase-knockout (GT-KO) pigs has increased expectations of clinical xenotransplantation, additional modifications of genetically engineered pigs are still being explored, because even GT-KO pigs are incapable of inhibiting the host's immunological response completely. One of the potential candidates is a complement-regulatory protein, such as human decay-accelerating factor (hDAF). However, there are few reports on how high the expression level of hDAF in pig cells would be required for suppression of complement activation. The purpose of this study was to examine the relationship between the level of hDAF expression and its inhibitory effect on human serum cytotoxicity. METHODS: An expression (pCAGGS) vector containing the hDAF gene was transfected into pig fibroblasts using an electroporation system (Gene Pulser II). Forty-eight to fifty-two hours after transfection, the cells were stained with FITC-labeled anti-hDAF antibody and then applied to the cell sorter. hDAF-transfected cells with various expression levels were collected by gating on fluorescence intensity. The level of hDAF expression was determined relative to that in human control endothelial cells. Collected cells expressing x1, x5, x10, x15 and x30 hDAF were incubated into 96-well plates for 16 h, and the cells were subjected to 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: hDAF expression levels in transfected cells at the time of MTT assay (16 h after sorting) were comparable to those immediately after sorting. hDAF expression in pig cells five times higher than in human endothelial cells was effective in inhibiting complement-dependent cytotoxicity of most human sera. However, 15- to 30-fold expression of hDAF was required for effective inhibition of human sera with the highest cytotoxic capacity. CONCLUSIONS: A much higher level of hDAF expression in pig cells than previously considered necessary might be required to provide additional benefit in inhibiting antibody-mediated rejection. Genetically engineered pigs that express very high levels of hDAF would be beneficial for xenotransplantation.

Animals↗

In vitro chemosensitivity test to predict chemosensitivity for paclitaxel, using human gastric carcinoma tissues.

BACKGROUND: Therapy guided by chemotherapy sensitivity and resistance assays may lead to rational treatment decisions. Paclitaxel, one of several new drugs for gastric carcinoma, has not been extensively evaluated by in vitro chemosensitivity tests. METHODS: Chemosensitivity testing by histoculture drug response assay (HDRA) was performed with fresh specimens of primary tumor from 113 patients with gastric carcinoma. The test was performed in medium containing paclitaxel at three different concentrations for the initial 45 samples. Correlations between the results of chemosensitivity testing, determined at the optimal concentration, and the patients' clinicopathologic factors and outcome were then assessed for all patients. RESULTS: By analyzing the initial 45 samples, 10 microg/ml was considered the optimal concentration of paclitaxel for this test. HDRA was successfully performed for 100 of 113 samples and chemosensitivity, calculated as the percentage of optical density of a tumor treated with anticancer drugs in relation to the optical density of the tumor cultured in the medium only, was distributed widely at this concentration. No significant correlation was observed between chemosensitivity and age, sex, clinical stage, histopathologic type, and outcome of patients with gastric carcinoma. CONCLUSION: A histoculture drug response assay can now be performed to predict the chemosensitivity of paclitaxel at the concentration found in the current study. The accuracy of the assay to actually predict survival needs to be validated by a prospective clinical trial involving patients who have received paclitaxel in the postoperative adjuvant setting.

Adult↗

Early detection of liver failure after hepatectomy by indocyanine green elimination rate measured by pulse dye-densitometry.

BACKGROUND/PURPOSE: Following a major hepatectomy, some degree of clinical and biochemical dysfunction occurs. Surgeons usually check serum total bilirubin levels to diagnose postoperative liver dysfunction. However, we cannot predict liver failure by biochemical data alone within the early postoperative period. Using newly developed pulse dye-densitometry (PDD), we measured serial postoperative indocyanine green elimination rate (ICG-K) values and investigated the possible relation between postoperative ICG-K values and complications. METHODS: Fifty-one patients scheduled for hepatectomy between January 2000 and December 2002 were enrolled. Pulse-dye densitometry was used to evaluate postoperative liver function. We analyzed the relation between postoperative ICG-K and postoperative outcome, assessed in terms of morbidity and mortality. RESULTS: Liver failure was seen in seven patients. The ICG-K value on postoperative day 1 in patients with liver failure was significantly lower than that in patients without liver failure (0.070 +/- 0.018 vs 0.152 +/- 0.056/min respectively; P < 0.001). There were no differences between preoperative ICG-K values in patients with and without liver failure. The sensitivity and specificity of an ICG-K value of less than 0.07 on postoperative day 1 were 71.4% and 95.5%, respectively, for predicting liver failure. CONCLUSIONS: We can measure the ICG-K value by PDD at the bedside without time delay, and we can predict liver failure in the early postoperative period by the ICG-K values on postoperative day 1. ICG-K values measured by PDD can provide important information for perioperative management.

Adult↗

Oncological problems in pancreatic cancer surgery.

Despite the development of more sophisticated diagnostic techniques, pancreatic carcinoma has not yet been detected in the early stage. Surgical resection provides the only chance for cure or long-term survival. The resection rate has increased due to recent advances in surgical techniques and the application of extensive surgery. However, the postoperative prognosis has been poor due to commonly occurring liver metastasis, local recurrence and peritoneal dissemination. Recent molecular-biological studies have clarified occult metastasis, micrometastasis and systemic disease in pancreatic cancer. Several oncological problems in pancreatic cancer surgery are discussed in the present review.

Chemotherapy, Adjuvant↗

Pilot study of oncolytic viral therapy using mutant herpes simplex virus (HF10) against recurrent metastatic breast cancer.

BACKGROUND: An oncolytic herpes simplex virus type 1 mutant (HF10) has been isolated and evaluated for antitumor efficacy in a syngeneic immunocompetent mouse model, where it was effective against cancer and conferred resistance to rechallenge with tumor cells in all surviving mice. Several studies have shown that HF10 is effective and safe for use against localized or peritoneally disseminated nonneuronal malignant tumors in animals. METHODS: A pilot study using HF10 was initiated in six patients with cutaneous or subcutaneous metastases from breast cancer. For each patient, .5 mL of HF10 suspension containing various viral doses was injected into one nodule; .5 mL of sterile saline was injected into another. All patients were monitored for local and systemic adverse effects. Nodules were excised 14 days after injection for histopathologic studies. RESULTS: All patients tolerated the intratumoral injection of HF10. No adverse effects occurred, and histopathological evaluation revealed 30% to 100% cancer cell death. CONCLUSIONS: This pilot study found HF10 to be safe and effective against metastatic breast cancer.

Aged↗

Chemotherapy as a component of multimodal therapy for gastric carcinoma.

Prognosis of locally advanced gastric cancer remains poor, and several multimodality strategies involving surgery, chemotherapy, and radiation have been tested in clinical trials. Phase III trial testing the benefit of postoperative adjuvant chemotherapy over treatment with surgery alone have revealed little impact on survival, with the exception of some small trials in Western nations. A large trial from the United States exploring postoperative chemoradiation was the first major success in this category. Results from Japanese trials suggest that moderate chemotherapy with oral fluoropyrimidines may be effective against less-advanced (T2-stage) cancer, although another confirmative trial is needed to prove this point. Investigators have recently turned to neoadjuvant chemotherapy, and some promising results have been reported from phase II trials using active drug combinations. In 2005, a large phase III trial testing pre- and postoperative chemotherapy has proven its survival benefit for resectable gastric cancer. Since the rate of pathologic complete response is considered to affect treatment results of this strategy, neoadjuvant chemoradiation that further increases the incidence of pathologic complete response could be a breakthrough, and phase III studies testing this strategy may be warranted in the near future.

Chemotherapy, Adjuvant↗

Biological significance of isolated tumor cells and micrometastasis in lymph nodes evaluated using a green fluorescent protein-tagged human gastric cancer cell line.

PURPOSE: The biological significance of isolated tumor cells and micrometastasis in lymph node defined by the International Union against Cancer remains essentially unknown because of the lack of appropriate animal models. In the present study, we developed a lymph node micrometastasis model featuring a human gastric cancer cell line tagged with green fluorescent protein gene (GCIY-EGFP), which allows visualization of even isolated tumor cells in the development of metastasis without histologic procedure. Using this model, we investigated the effect of surgery and chemotherapy on the growth of early-phase metastasis formation in the lymph nodes. EXPERIMENTAL DESIGN: The time course of spontaneous inguinal lymph node metastasis after s.c. inoculation of GCIY-EGFP cells into nude mice was examined with fluorescence dissecting microscopy. Then, the effects of surgical removal of the primary tumor with or without anti-asialo GM1 treatment or postoperative chemotherapy on the growth of isolated tumor cells and micrometastasis in the lymph nodes were examined. RESULTS: GCIY-EGFP cells were found to metastasize spontaneously to the inguinal lymph nodes to form isolated tumor cells, micrometastasis, and, finally, develop macroscopic metastasis at 1 to 2, 3 to 5, and 5 weeks postinjection, respectively. When the primary tumors were removed within 2 weeks of inoculation, isolated tumor cells, but not micrometastasis, in the lymph nodes regressed by 4 weeks after surgery in all the mice examined (five of five). This spontaneous regression of isolated tumor cells was completely reversed by anti-asialo GM1 treatment, which could deplete natural killer cells effectively in nude mice. Chemotherapy following resection of the primary tumor at an early stage partially eliminated the remaining micrometastasis in the lymph nodes. CONCLUSIONS: These results suggest that isolated tumor cells in the regional lymph nodes regressed by removal of the primary tumor mainly via natural killer cell-mediated antitumor activity and that micrometastasis in the lymph nodes could be effectively eliminated by the postoperative chemotherapy.

Animals↗

Overexpression of pituitary tumor transforming gene 1 in HCC is associated with angiogenesis and poor prognosis.

The pituitary tumor transforming gene 1 (PTTG1) protein is cell-cycle regulated and is identified as a human securin that inhibits sister chromatid separation and is involved in transformation and tumorigenesis. PTTG1 has very low or undetectable expression in most normal human tissues, but it is abundantly expressed in malignant cell lines and pituitary tumors. In this study, we investigated human PTTG1 expression in 62 hepatocellular carcinoma (HCC) specimens using quantitative real-time reverse transcription polymerase chain reaction analysis. We found that, compared with corresponding noncancerous liver tissues, PTTG1 was remarkably overexpressed in HCCs (PTTG1/beta-actin; 0.443 +/- 0.073 vs. 0.068 +/- 0.007; P < .0001). Furthermore, we found a significant correlation between PTTG1 expression and serum alpha-fetoprotein level (P < .001). Univariate and multivariate analyses revealed that the PTTG1 messenger RNA (mRNA) expression was an independent prognostic factor for disease-free (odds ratio 2.70; P = .037) and overall (odds ratio 5.35; P = .007) survival. Moreover, we discovered a significant relationship between PTTG1 expression and intratumoral microvessel density. Our data supported an important role for PTTG1-mediated upregulation of fibroblast growth factor (FGF)-2, one of angiogenesis and modulation of tumor progression, in hepatocarcinogenesis. In conclusion, PTTG1 might be critically involved in the development of HCCs through the promotion of angiogenesis. PTTG1 is overexpressed in HCC and our results suggest that PTTG1 mRNA expression has prognostic significance for the survival of postoperative patients with HCC.

Adult↗

Indications and techniques of extended resection for pancreatic cancer.

INTRODUCTION: The resectability rate and postoperative survival rate for pancreatic carcinoma are poor. Aggressive resection including vascular resection and extended lymphadenectomy represent one strategy for improving survival. This study was carried out to clarify the indications for extended resection, especially vascular resection, for pancreatic carcinoma. METHODS: From July 1981 to March 2005, we performed curative resection in 289 of 443 patients with pancreatic carcinoma in our department (65.2%). Vascular resection was performed in 201 (69.5%) patients and portal vein resection without arterial resection in 186 patients. Combined portal and arterial resection was performed in 14 patients and arterial resection without portal vein resection in 1. Extended lymphadenectomy including paraaortic lymph nodes was done. The postoperative survival rate was stratified according to operative and pathology findings. RESULTS: Operative mortality (any death within 30 days after surgery) occurred in 11 of the 289 curative resection patients (3.8%), including 1 of 88 patients without vascular resection (1.1%), 5 of 186 portal vein resection patients without arterial resection (2.7%), and 5 of 14 (35.7%) arterial resection patients undergoing portal vein arterial resection as well. Most patients who survived for 2 to 3 years had carcinoma-free surgical margins. CONCLUSIONS: The most important indication for vascular resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, vascular resection is contraindicated. Extended lymphadenectomy may be not of benefit.

Anastomosis, Surgical↗

Is pancreaticogastrostomy safer than pancreaticojejunostomy?

BACKGROUND/PURPOSE: Failure of a pancreatic-enteric anastomosis very frequently leads to morbidity and mortality after pancreaticoduodenectomy. Pancreaticojejunostomy or pancreaticogastrostomy is often used after pancreaticoduodenectomy. The many reports on pancreaticogastrostomy support the low rates of anastomotic leakage and mortality compared with pancreaticojejunostomy. METHODS: Between January 1995 and December 2004, 155 pancreaticojejunostomies and 58 pancreaticogastrostomies were performed after pancreatic resection in the Second Department of Surgery of Nagoya University Hospital. Postoperative morbidity and mortality were analyzed. RESULTS: The incidence of pancreatic fistula was similar for the pancreaticojejunostomy (12.2%) and pancreaticogastrostomy (20.7%) groups and the mortality rate was 0% in both groups. CONCLUSIONS: This restrospective clinical study suggested no significant difference in the incidence rate of pancreatic fistula and mortality between pancreaticojejunostomy and pancreaticogastrostomy.

Adult↗

A new method of thermo-chemotherapy using a stent for patients with esophageal cancer.

PURPOSE: Many patients with advanced esophageal cancer have a stent inserted in the esophagus, but very little else can be done. We devised a new method of delivering thermotherapy using an implant heating system (IHS) with a metallic stent. To our knowledge, there are no other reports of thermotherapy using metallic stents. We report our clinical results of treating patients with this new technique. METHODS: A metallic stent was placed in the esophagus and heated for thermotherapy. This was combined with simultaneous chemotherapy in 13 patients and radio-chemotherapy in 5 patients. Each thermotherapy session consisted of heating the stent to 50 degrees C for 10 min. These 18 patients received a collective 52 sessions of thermotherapy. The tumor was excised after this treatment in 5 of these 18 patients. RESULTS: We evaluated 17 of the 18 patients, after the exclusion of 1 patient who underwent radio-chemotherapy before placement of the stent. There was 1 complete response (CR) and 12 partial responses (PR), accounting for 76%. The patient with a CR had no residual cancer cells detected by pathologic examination after surgical resection. Thermotherapy proved effective in 8 (89%) of 9 patients who received this treatment at least three times. It was effective in all (100%) patients who underwent concomitant radio-chemotherapy. CONCLUSIONS: Our results show that thermotherapy using a stent can improve the effectiveness of combination therapy, suppress local tumor growth, and enhance quality of life over a long period.

Aged↗

Adrenal incidentaloma: review of 197 patients and report of a drug-related false-positive urinary normetanephrine result.

PURPOSE: To determine the incidence and importance of functioning tumors among incidentally discovered adrenal masses in the era of laparoscopic surgery. METHODS: We defined adrenal incidentaloma as a tumor detected during abdominal imaging for adrenal-unrelated reasons, and we reviewed 197 consecutive patients with adrenal incidentaloma diagnosed since we started laparoscopic adrenalectomy. RESULTS: Incidentaloma was discovered initially in 91 (46%) patients and pheochromocytoma was detected as an incidentaloma in 21 (39%) of 54 patients. One patient, a 21-year-old woman taking mesalamine for ulcerative colitis, had a remarkably elevated urinary normetanephrine level, which resulted in the initial misdiagnosis of a 10-cm right adrenal incidentaloma as a pheochromocytoma. Laparoscopic right adrenalectomy resulted in a pathological diagnosis of ganglioneuroma. A series of urinary normetanephrine measurements were taken in parallel with the mesalamine doses. We found that other patients medicated with mesalamine, without adrenal tumors, had elevated urinary normetanephrine levels, confirming that mesalamine metabolites interfere with urinary normetanephrine measurements. CONCLUSIONS: It is essential to diagnose the functional potential of adrenal incidentaloma preoperatively, and not to perform laparoscopic adrenalectomy for adrenal incidentaloma without careful evaluation first.

Adrenal Gland Neoplasms↗

Surgical significance of undescended parathyroid gland in renal hyperparathyroidism.

BACKGROUND: In renal hyperparathyroidism, in which basically all parathyroid glands are hyperplastic, overlooking one undescended parathyroid gland becomes important. METHODS: Between July 1973 and December 2004, 1750 patients in our department underwent parathyroidectomy for severely advanced renal hyperparathyroidism. We evaluated the frequency and location of undescended parathyroid glands and the clinical findings and the prognosis of patients with such glands. RESULTS: Undescended parathyroid glands in our series of renal hyperparathyroidism numbered 16 of 1750 cases (0.91%). In 9 patients, the glands were removed at the initial parathyroidectomy in our hospital. Two of these glands were detected by preoperative imaging; 6 glands were removed with an undescended thymus. The mean weight of the undescended parathyroid glands that were removed at initial operations was 470 mg (30 to 1392 mg). In 7 other patients, unrecognized undescended glands were responsible for persistent hyperparathyroidism in 6 patients and recurrent disease in 1 patient. In 4 of these 7 patients, the initial parathyroidectomy was performed at our hospital; in the other 3 patients, the initial parathyroidectomy had been done at another hospital, and the glands were removed on reoperation. The mean weight of these glands was 1295 mg (range, 444-2396 mg). In 12 of a total of 16 patients with undescended glands, there appeared to be an inferior parathyroid gland, and the other 4 glands appeared to be a superior gland. No glands were detected by sestamibi scans. CONCLUSION: In operations for renal hyperparathyroidism, an undescended parathyroid gland can be readily overlooked, which leads to persistent or recurrent hyperparathyroidism. Because an undescended parathyroid gland is not always an inferior gland, in surgery for persistent and/or recurrent renal hyperparathyroidism, it is very important to examine carefully the submandibular portion to detect such an undescended gland.

Adult↗

Plasminogen activator inhibitor-1 as a potential marker for the malignancy of gastric cancer.

To test the hypothesis that plasminogen activator inhibitor-1 (PAI-1) may serve as a candidate marker for the malignancy of gastric cancer, we carried out quantitative reverse transcription-polymerase chain reaction for the PAI-1 gene and evaluated the possible relationship between PAI-1 gene expression levels and clinicopathological findings in gastric cancer. A significant increase in PAI-1 expression scores was observed in lymph node metastasis-positive gastric cancers (2.11 +/- 0.35) compared to metastasis-negative cancers (0.33 +/- 0.49) (P = 0.0048), as well as in distant metastasis-positive gastric cancers (3.68 +/- 0.58) compared to metastasis-negative cancers (1.20 +/- 0.32). The PAI-1 expression score markedly increased with tumor stage (P < 0.0001; ANOVA test). Moreover, multivariate analysis revealed the PAI-1 expression score to be a strong and independent prognostic factor for gastric cancer (P = 0.0450). These results suggested that PAI-1 might serve as a new and promising parameter for the prediction of prognosis in gastric cancer.

Adult↗

Is absorption profile of cyclosporine really important for effective immunosuppression?

The clinical significance of cyclosporine (CsA) concentration 2 h postdose (C(2)) monitoring is widely recognized in organ transplantation, because C(2) value is considered to be a predictable surrogate marker of full area under the concentration-time curve (AUC), and/or a peak concentration value exhibits potent inhibition of calcineurin activity. However, the pharmacological advantage of absorption profile (AP) has not been fully elucidated. In a rat skin allotransplantation model, the authors evaluated the efficacy of AP by different dosage regimens (20, 25 or 30 mg/kg/d, once or twice daily) and routes (p.o. or i.v.), and examined whether high C(2) or AUC(0-4) is intrinsically valuable for effective immunosuppression. Graft survival was CsA dose-dependent and correlated with full AUC(0-24), rather than AP. The difference between the once and twice daily administrations did not influence full AUC(0-24) or immunosuppressive effect. Continuous intravenous infusion with flat pharmacokinetics also produced adequate immunosuppression as was observed in enteral administration at the same level of total exposure. The impact of high peak concentration in AP on immunosuppressive effect could not be found. It was suggested that AP would not have intrinsic pharmacodynamic value. However, absorption profiling was considered to be clinically useful in that C(2) value is a good surrogate marker of total exposure (AUC(0-24)).

Absorption↗

Differential expression of cyclin-dependent kinase inhibitors, p27Kip1 and p57Kip2, by corticotropin in rat adrenal cortex.

An important role for the cyclin-dependent kinase inhibitors (CDKIs), p27Kip1 and p57Kip2, in the proliferation and differentiation of adrenal cells has been suggested by their knockout mice, which display adrenal hyperplasia. Adrenal development and function are primarily regulated by ACTH. In the present study, we investigated the effects of ACTH on the expression of p27Kip1, p57Kip2 and proliferating cell nuclear antigen (PCNA) in rat adrenals. Male Wistar rats were treated with dexamethasone (Dex) to inhibit endogenous ACTH secretion. ACTH was then administered to the rats, and the adrenals were examined by Western blot and immunohistochemical analyses. Dex treatment induced shrinkage of adrenals where no PCNA-expressing cells were detected, but most of the cells expressed p27Kip1. Subsequent ACTH treatment resulted in the marked suppression of p27Kip1 expression, specifically in adrenocortical cells at 12 h after the stimulus. At 48 h, the p27Kip1 suppression still continued in the cortex, while the PCNA-expressing cells appeared mainly around the zona glomerulosa and increased at 72 h. At this time, the p27Kip1-expressing cells also appeared in the same zone. In contrast to p27Kip1, the expression of p57Kip2 was not detected in the Dex-treated adrenal. However, its expression was markedly induced by ACTH in the zona glomerulosa at 48 and 72 h. The results demonstrate that the primary site for mitogenic action of ACTH in rat adrenocortex is the zona glomerulosa, and that ACTH modulates proliferation of adrenocortical cells by regulating p27Kip1 and p57Kip2 expression in a time- and site-specific manner.

Adrenal Cortex↗