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Biomedical subjects

K Kubota

Publications and source records attributed to K Kubota.

At least 37 records · Page 2Linked to original sources

Laparoscopic resection of gastrointestinal mesenchymal tumors located in the upper stomach.

BACKGROUND: The treatment strategy for a gastrointestinal mesenchymal tumor located close to the esophagogastric junction remains controversial. The authors evaluate the criteria indicating that a gastrointestinal mesenchymal tumor is suitable for laparoscopic resection and assess the surgical techniques on the basis of clinical outcomes. METHODS: The criteria specified a tumor more than 2 cm in diameter or a tendency for it to increase in size during the follow-up period. For eight patients in whom the tumor was located within 3 cm of the esophagogastric junction, an intragastric laparoscopic approach was used, whereas for seven patients in whom the tumor was further from the esophagogastric junction, an exogastric approach was used. RESULTS: In all 15 cases, the laparoscopic resection was successful, with no complications. The intragastric group had a mean maximal tumor size of 2.9 cm, a mean operation time of 168 min, and a mean postoperative hospital stay of 8.8 days, whereas these values in the exogastric group, were respectively, 3.9 cm, 121 min (p = 0.0442), and 9.6 days. There were no recurrences in either group during the follow-up period. CONCLUSION: The good clinical outcomes suggest hat the criteria used as an indication for laparoscopic resection and the surgical techniques applied were appropriate for the resection of gastrointestinal mesenchymal tumors.

Aged↗

A two-dimensional mathematical model of percutaneous drug absorption.

BACKGROUND: When a drug is applied on the skin surface, the concentration of the drug accumulated in the skin and the amount of the drug eliminated into the blood vessel depend on the value of a parameter, r. The values of r depend on the amount of diffusion and the normalized skin-capillary clearance. It is defined as the ratio of the steady-state drug concentration at the skin-capillary boundary to that at the skin-surface in one-dimensional models. The present paper studies the effect of the parameter values, when the region of contact of the skin with the drug, is a line segment on the skin surface. METHODS: Though a simple one-dimensional model is often useful to describe percutaneous drug absorption, it may be better represented by multi-dimensional models. A two-dimensional mathematical model is developed for percutaneous absorption of a drug, which may be used when the diffusion of the drug in the direction parallel to the skin surface must be examined, as well as in the direction into the skin, examined in one-dimensional models. This model consists of a linear second-order parabolic equation with appropriate initial conditions and boundary conditions. These boundary conditions are of Dirichlet type, Neumann type or Robin type. A finite-difference method which maintains second-order accuracy in space along the boundary, is developed to solve the parabolic equation. Extrapolation in time is applied to improve the accuracy in time. Solution of the parabolic equation gives the concentration of the drug in the skin at a given time. RESULTS: Simulation of the numerical methods described is carried out with various values of the parameter r. The illustrations are given in the form of figures. CONCLUSION: Based on the values of r, conclusions are drawn about (1) the flow rate of the drug, (2) the flux and the cumulative amount of drug eliminated into the receptor cell, (3) the steady-state value of the flux, (4) the time to reach the steady-state value of the flux and (5) the optimal value of r, which gives the maximum absorption of the drug. The paper gives valuable information which can be obtained by this two-dimensional model, that cannot be obtained with one-dimensional models. Thus this model improves upon the much simpler one-dimensional models. Some future directions of the work based on this model and the one-dimensional non-linear models that exist in the literature, are also discussed.

Humans↗

Degradation pathways of cyclic alkanes in Rhodococcus sp. NDKK48.

The degradation pathways for cyclic alkanes (c-alkanes) in Rhodococcus sp. NDKK48 were investigated. Strain NDKK48 used dodecylcyclohexane as a sole carbon and energy source, and five metabolites in the dodecylcyclohexane degradation pathway were detected by gas-chromatography/mass spectra. The metabolites were identified as cyclohexanecarboxylic acid, cyclohexylacetic acid, 1-cyclohexene-1-acetic acid, 4-dodecylcyclohexanol, and 4-dodecylcyclohexanone. The strain degrades dodecylcyclohexane via a ring oxidation pathway and an alkyl side chain oxidation pathway. Cyclohexanecarboxylic acid was further oxidized to muconic acid via 1-cyclohexene-1-carboxylic acid and benzoic acid, and the muconic acid was finally used by strain NDKK48 for growth. Methylcyclohexane and cyclohexane were co-oxidized with hexadecane by strain NDKK48. Methylcyclohexane was degraded via a ring oxidation pathway, and the degradation pathway contained part of the Baeyer-Villiger oxidation for ring cleavage. Cyclohexane was also degraded by the same pathway as methylcyclohexane. Thus, strain NDKK48 has two pathways for the complete degradation of c-alkanes.

Biodegradation, Environmental↗

A seasonal variation in the onset of postoperative adhesive small bowel obstruction is related to changes in the climate.

BACKGROUND: Postoperative small bowel obstruction following abdominal procedures is more common in patients who have undergone laparotomy. However, little is known about the influence of climate on the incidence of postoperative small bowel obstruction. METHODS: To evaluate whether seasonal climatic variations are a risk factor for postoperative small bowel obstruction, hospital-based, retrospective case series was designed from medical records of 230 patients suffering from postoperative small bowel obstruction admitted to the Tokyo University Branch Hospital. Detailed analysis of weather charts from the Japanese Meteorological Agency and review of medical records for selected patients who were diagnosed with postoperative small bowel obstruction. The obstruction was diagnosed by abdominal X-ray imaging, clinical examination, and patient interviews. RESULTS: A total of 233 patients diagnosed with postoperative small bowel obstruction were identified. Analysis of the medical records of these 233 patients revealed that the variables associated with an increased risk of postoperative small bowel obstruction included low ambient temperatures of 5-10 degrees C, an increase in air humidity by 40-50% and air pressure of 1010-1015 hPa. CONCLUSION: The typical winter weather in Tokyo is characterised by low temperatures, low humidity and moderate air pressure. These winter climate conditions could be correlated with an increased incidence of postoperative small bowel obstruction in Tokyo during our period.

Adolescent↗

Efficacy of droperidol in the prevention of cisplatin-induced delayed emesis: a double-blind, randomised parallel study.

We conducted a prospective, randomized, double-blind, parallel study comparing the antiemetic activity and tolerability of treatment with droperidol (2.5 mg d.i.v. twice daily for 5 days) and placebo, both combined with granisetron (3 mg d.i.v. on the first day) and dexamethasone (16 mg d.i.v. on the first day, 8 mg d.i.v. on days 2, 3, and 4 mg d.i.v. on days 4, 5). A total of 180 lung cancer patients receiving high-dose cisplatin (80 mg/m(2))-containing chemotherapy were enrolled in the study, and 171 of them were capable of being evaluated. The clinical characteristics of the patients in the two treatment arms were well balanced. Complete protection from nausea and vomiting was recorded in the acute phase in 97% of patients who treated with droperidol versus 98% of patients who given the placebo (P=0.920), and in 42% versus 38% in the delayed phase (P=0.615). The multiple logistic regression analysis showed that a history of motion sickness was a significant risk factor for cisplatin-induced delayed emesis (odds ratio [OR]=5.98; 95% CI=2.15 to 16.7, P=0.0006). Droperidol-containing treatment was well tolerated by most patients, however, the incidence of sleepiness in the droperidol group was higher than in the placebo group (69% versus 30%, P<0.0001). In conclusion, our data did not support the hypothesis that addition of droperidol to granisetron and dexamethasone reduces the delayed emesis induced by high-dose cisplatin.

Adult↗

A phase II study of cisplatin and docetaxel administered as three consecutive weekly infusions for advanced non-small-cell lung cancer in elderly patients.

BACKGROUND: To evaluate the efficacy and safety of treatments for advanced non-small-cell lung cancer in elderly patients aged 75 years or older, we conducted a phase II study of cisplatin and docetaxel administered in three consecutive weekly infusions. PATIENTS AND METHODS: The eligibility criteria for the study included the presence of chemotherapy-naive advanced non-small-cell lung cancer, age > or =75 years, Eastern Cooperative Oncology Group performance status of 0 or 1, a measurable lesion, adequate organ functions and signed informed consent. The chemotherapy regimen consisted of cisplatin (25 mg/m(2)) and docetaxel (20 mg/m(2)) on days 1, 8 and 15 every 4 weeks. RESULTS: Between February 2000 and March 2002, 34 elderly patients with non-small-cell lung cancer were enrolled in the study and 33 patients were treated. Two complete responses and 15 partial responses were obtained for an objective response rate of 52% in 33 treated patients. The median survival period was 15.8 months, and the 1-year survival rate was 64%. Toxicities were mild with no grade 4 toxicities. Only grade 3 leukopenia (6%), neutropenia (12%), anemia (3%), hyponatremia (3%) and nausea/vomiting (3%) were observed. CONCLUSION: Cisplatin and docetaxel administered in three consecutive weekly infusions was safe and effective for the treatment of elderly patients with chemotherapy-naive non-small-cell lung cancer.

Aged↗

Video-assisted bullectomy using needlescopic instruments for spontaneous pneumothorax.

Patients with spontaneous pneumothorax require immediate insertion of a chest drain to evacuate the intrathoracic air. During video-assisted bullectomy, we made use of an existing chest drain hole to insert a thoracoscope or an endoscopic linear stapler. Video-assisted bullectomy was performed through three ports-two 2-mm ports and the existing chest drain hole. Therefore, no new skin incisions were required for the insertion of the 2-mm ports. A chest drain was again inserted via the existing chest drain hole after bullectomy. This procedure was used on 8 of 10 patients with spontaneous pneumothorax. There were no postoperative complications or recurrences. Thoracoscopic bullectomy using needlescopic instruments is technically feasible, safe, and effective. Currently, the procedure is indicated only for simple cases and not for the lysis of adhesions.

Endoscopes↗

Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer: JCOG 9507.

Combinations of cisplatin-irinotecan and cisplatin-etoposide are active and well tolerated in patients with both small-cell lung cancer (SCLC) and nonsmall-cell lung cancer (NSCLC). To define the recommended dose for phase II trials of irinotecan combined with cisplatin and etoposide in chemonaive patients with stage IV disease, 56 patients (11 having SCLC and 45 NSCLC) received cisplatin 25 mg m(-2) weekly for 9 weeks, etoposide 60 mg m(-2) for 3 days on weeks 1, 3, 5, 7 and 9, and irinotecan 20-100 mg m(-2) (levels 1-8) on weeks 2, 4, 6 and 8, together with a prophylactical granulocyte colony-stimulating factor support (50 microg m(-2) on days 4-7 on weeks 1, 3, 5, 7 and 9, and on days 2-7 on weeks 2, 4, 6 and 8). Grade 3-4 leukocytopenia, neutropenia and thrombocytopenia were noted in 20 (36%), 28 (50%) and nine (16%) patients, respectively. Grade 3 diarrhoea, grade 3 cardiac toxicity, and grade 4 transaminase elevation developed in one (1.8%) patient each. Totally, four of 56 patients were removed from the study because of toxicity and recovered, and two other patients died in situations where drug toxicity might contribute to their death. Dose-limiting toxicity was noted in less than one-third of patients at dose levels 1-7, but in all patients at dose level 8. Thus, the recommended dose was determined to be level 7 (irinotecan 90 mg m(-2)). The response rates for SCLC and NSCLC were 91% (10/11) and 38% (17/45), respectively. The median survival time and 1-year survival rate were 11.9 months and 46% for SCLC and 10.1 months and 40% for NSCLC, respectively. This regimen was considered to be feasible and promising for the treatment of stage IV SCLC and NSCLC.

Adult↗

Triplet chemotherapy with vinorelbine, gemcitabine, and cisplatin for advanced non-small cell lung cancer: a phase II study.

We conducted a phase II trial of triplet chemotherapy consisting of vinorelbine, gemcitabine, and cisplatin in patients with advanced non-small cell lung cancer to assess its efficacy and toxicity. Thirty-three patients with chemotherapy-naïve stage IIIB disease (n=8), stage IV disease (n=23), or recurrence after surgical resection (n=2) were given intravenous infusions of vinorelbine 25 mg m(-2), gemcitabine 1000 mg m(-2), and cisplatin 40 mg m(-2) on days 1 and 8 at 3-week intervals. There were 16 partial responses, and the objective response rate was 48% (95% confidence interval: 31-66%). The median survival time was 13.5 months (95% confidence interval: 10.6-16.4 months), and the one-year survival rate was 61%. Grade 4 haematologic toxicity consisted of neutropenia in 72% of patients, and febrile neutropenia occurred in 42% of the patients. There was one toxic death, and it was attributed to neutropenic fever and haemoptysis. Autopsy revealed diffuse pulmonary haemorrhage secondary to bacterial abscesses and vasculitis in both lungs. The common nonhaematologic toxicities included grade 2-3 nausea (39%) and vomiting (18%). Triplet chemotherapy containing vinorelbine, gemcitabine, and cisplatin is effective in the treatment of chemo-näive patients with advanced non-small cell lung cancer, but produces unacceptable frequent febrile neutropenia.

Adult↗

Laparoscopic resection of the pancreas and review of the literature.

BACKGROUND: Laparoscopic pancreatic surgery still is not a common procedure worldwide. Postoperative complications such as a pancreatic leakage cause a serious condition. We report our consecutive laparoscopic pancreatic resections of islet cell tumors or benign diseases and their outcomes. METHOD: Laparoscopic pancreatic resections were attempted in three patients. Preoperative diagnoses were insulinoma in two patients and cystadenoma in one patient. The lesions were located in the pancreas body in two patients and the pancreas tail in one patient. Their sizes ranged from 1 to 6 cm in diameter (mean, 3 cm). RESULTS: We performed distal pancreatectomy using an endoscopic linear stapler with conservation of the spleen in two patients and enucleation in one patient. Of the distal pancreatectomies, the splenic artery and vein were preserved in one patient, whereas in the other they were divided. There were no perioperative complications in any of the cases. The mean postoperative hospital stay was 10 days (range, 7-14 days). There were no episodes of hypoglycemia or recurrence during the mean follow-up period of 25 months (range, 11-36 months). CONCLUSIONS: Although laparoscopic pancreatic resection of selected patients is a feasible and safe procedure in the hands of experienced laparoscopic surgeons, patients must be carefully observed after surgery to avoid serious conditions by pancreatic fistula.

Adult↗

A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs.

In a previous study, we used subcutaneous LY80 tumours (a subline of Yoshida sarcoma), Sato lung carcinoma, and methylcholanthrene-induced primary tumours, to demonstrate that a novel water-soluble combretastatin A-4 derivative, AC7700, abruptly and irreversibly stopped tumour blood flow. As a result of this interrupted supply of nutrients, extensive necrosis was induced within the tumour. In the present study, we investigated whether AC7700 acts in the same way against solid tumours growing in the liver, stomach, kidney, muscle, and lymph nodes. Tumour blood flow and the change in tumour blood flow induced by AC7700 were measured by the hydrogen clearance method. In a model of cancer chemotherapy against metastases, LY80 cells (2x10(6)) were injected into the lateral tail vein, and AC7700 at 10 mg x kg(-1) was injected i.v. five times at intervals of 2 days, starting on day 7 after tumour cell injection. The number and size of tumours were compared with those in the control group. The change in tumour blood flow and the therapeutic effect of AC7700 on microtumours were observed directly by using Sato lung carcinoma implanted in a rat transparent chamber. AC7700 caused a marked decrease in the tumour blood flow of all LY80 tumours developing in various tissues and organs and growth of all tumours including lymph node metastases and microtumours was inhibited. In every tumour, tumour blood flow began to decrease immediately after AC7700 administration and reached a minimum at approximately 30 min after injection. In many tumour capillaries, blood flow completely stopped within 3 min after AC7700 administration. These results demonstrate that AC7700 is effective for tumours growing in various tissues and organs and for metastases. We conclude that tumour blood flow stanching induced by AC7700 may become an effective therapeutic strategy for all cancers, including refractory cancers because the therapeutic effect is independent of tumour site and specific type of cancer.

Animals↗

Synergistic effect of fibroblast growth factor-4 in ectopic bone formation induced by bone morphogenetic protein-2.

Bone morphogenetic protein family members (BMPs) are essential signaling molecules during limb development and, in this process, fibroblast growth factor family members (FGFs) cooperate with BMPs. FGFs also exert anabolic effects in bone when systemically or locally applied. Thus, it is likely that the cooperation with FGFs also occurs in BMP-induced ectopic bone formation and that the exogenous FGF application would promote this bone formation. In the present study, after subcutaneously implanting recombinant human BMP-2 (rhBMP-2) in rats, we examined the expression of FGF-4 and FGF receptors (FGFRs) mRNAs and the effect of exogenous recombinant human FGF-4 (rhFGF-4) on bone formation. Three days after implantation, the pellets containing rhBMP-2 were surrounded by fibroblastic mesenchymal cells; on day 7, cartilage tissue appeared; on day 10, hypertrophic chondrocytes and a small amount of mineralized tissue were observed; and, on day 14, the amount of mineralized tissue increased. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that FGF-4 expression appeared at early stages (days 3 and 7) and its expression decreased at later stages (days 10, 14, and 21), whereas FGFRs were expressed continuously. In situ hybridization revealed that, on days 3 and 7, FGF-4, and FGFR subtypes 1 and 2 (FGFR-1 and FGFR-2) were expressed in mesenchymal cells and chondrocytes, and in the area of alkaline phosphatase (ALP) expression. On day 10, FGF-4 was not detected, whereas the expression of FGFR-1 and FGFR-2 was detectable in the area of alkaline phosphatase (ALP) expression. Injection of rhFGF-4 on days 2, 3, and 4 enhanced the mineralized tissue formation induced by rhBMP-2; however, neither rhFGF-4 treatment on days 6, 7, and 8 nor rhFGF-4 treatment on days 9, 10, and 11 influenced the amount of rhBMP-2-induced mineralization. Our results indicate that FGF-4 and FGFR signals play important roles during rhBMP-2-induced bone formation. We further suggest that the combination of rhBMP-2 and rhFGF-4 would be useful for bone augmentation.

Animals↗

Arterial reconstruction in Buerger's disease: by-pass to disease-free collaterals.

BACKGROUND: Arterial reconstructions for ischemia in patients with Buerger's disease are technically challenging. This retrospective review was conducted to identify the critical factor for a successful outcome in bypass surgery for Buerger's disease. METHODS DESIGN OF STUDY: retrospective review. SETTING: University hospital, hospitalized patients. PATIENTS: since 1993, we performed 10 arterial reconstructions in 8 patients with Buerger's disease. There were 8 tibial artery bypasses and 2 collateral artery bypasses. One bypass was performed in the upper extremity. INTERVENTIONS: bypass surgery with autogenous vein graft. MAIN OUTCOMES MEASUREMENTS: graft patency. RESULTS: Over a mean follow-up period of 41.8 months, there were 3 graft occlusions. Of these, 2 were of bypasses to a patent but diseased tibial artery. One graft was occluded due to a toe stenosis which had been previously detected. The 2 collateral artery bypasses were patent at the last follow-up. CONCLUSIONS: In Buerger's disease, distal arterial reconstruction is frequently necessary to prevent ischemic limb loss. Collateral artery bypass is an option when the main arteries are affected by the disease. A patent but diseased artery should be avoided as a target for reconstruction.

Adult↗

Experience with endoscopic axillary lymphadenectomy using needlescopic instruments in patients with breast cancer: a preliminary report.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of endoscopic axillary lymphadenectomy using needlescopic instruments in patients with breast cancer. METHODS: Five patients with breast cancer were treated by partial mastectomy and endoscopic axillary lymphadenectomy. We evaluated the results of the surgical procedure and the postoperative course. RESULTS: In all the patients, endoscopic axillary lymphadenectomy was performed successfully. The mean duration of the operation was 105.4 min, the mean blood loss 19.4 ml, and the mean number of dissected axillary lymph nodes 13. There were no intra- or postoperative complications. The mean amount of lymphorrhea was 131.2 ml, and the mean duration of drainage was 3.6 days. No postoperative analgesics were administered. CONCLUSIONS: Endoscopic axillary lymphadenectomy can be performed safely with needlescopic instruments, but further study is needed to establish this technique.

Aged↗

Spleen-preserving laparoscopic distal pancreatectomy with conservation of the splenic artery and vein for a large insulinoma.

We report a successful spleen-preserving laparoscopic distal pancreatectomy for a large insulinoma with conservation of the splenic artery and vein. The patient was a 48-year-old man with syncope due to hypoglycemia. Abdominal computed tomography (CT) and ultrasonography revealed a large 6-cm mass located in the tail of the pancreas. We adopted the laparoscopic approach to remove the tumor. After careful dissection and an accurate hemostasis between the pancreas and splenic vessels, laparoscopic distal pancreatectomy was carried out using a linear stapler. There were no perioperative complications. The patient was discharged uneventfully. He had no hypoglycemic episodes or abdominal symptoms during 8 months of follow-up. When performed by experienced laparoscopic surgeons in conjunction with intraoperative ultrasonography, spleen-preserving laparoscopic distal pancreatectomy with conservation of the splenic artery and vein is a technically feasible procedure for the treatment of benign lesions of the tail or body of the pancreas.

Humans↗

Laparoscopic resection of a functional paraganglioma in the organ of Zuckerkandl.

We describe the successful laparoscopic resection of a functional paraganglioma in the organ of Zuckerkandl. A 47-year-old man with hypertension and diabetes mellitus was found to have an abdominal mass beside the aorta. The tumor was diagnosed as a functional paraganglioma by diagnostic imaging and biochemical tests. We then performed a transperitoneal laparoscopic resection for removal. After freeing the left ureter, resecting the inferior mesenteric artery, and dividing the small blood vessels, the tumor was isolated and found to be preserved in its capsule. It was retrieved in a bag through an enlarged incision. The operation time was 450 min and blood loss was 410 ml. The postoperative course was uneventful and there has been no local recurrence or distant metastasis during the 18-month follow-up period. Laparoscopic resection of functional extraadrenal paragangliomas is technically feasible and safe if adequate pre- and intraoperative medical management and a careful, steady surgical technique are used.

Abdominal Neoplasms↗