Biomedical subjects
Publications and source records attributed to M Kitajima.
A gastric tube-to-airway fistula is a very rare complication after esophageal reconstruction. A patient with a gastric tube-to-tracheal fistula that developed more than 9 years after surgery for cancer of the cervical esophagus was treated with transposition of a pedicled latissimus dorsi myocutaneous flap. Careful perioperative respiratory management helped save the patient's life.
Genomic instability is sometimes due to impairment of DNA repair systems, which results in a change in the number of microsatellite repeats in tumor cells, produced by slippage during DNA replication. Such abnormal repeats are manifested as microsatellite instability (MSI). We have devised a simple assay using four-color fluorescence for the detection of MSI by an automatic sequencer. Using this method, MSI and loss of heterozygosity (LOH) at four microsatellite loci can be identified simultaneously. We have also developed an algorithm and software for automated analysis of MSI and LOH with this method. Using our method for the detection of MSI in four microsatellite loci and the algorithm and software that we developed, 18 (94.7%) of 19 patients with hereditary nonpolyposis colorectal cancer (HNPCC), meeting the Amsterdam Minimum Criteria, were found to exhibit MSI.
BACKGROUND/PURPOSE: This report describes a technique of hepatic portoenterostomy (HPE) to keep sustained bile drainage in biliary atresia patients. In conventional HPE, the medial posterior row of the anastomosis is placed behind the main portal vein. But around both lateral corners where the portal branches enter the liver parenchyma, the anastomosis is placed across and outside of the portal veins. Resultantly, the proximal part of the portal veins become included in anastomosis attaching directly to the dissected area where bile ducts are copious. In a devised procedure designated as invaginating anastomosis (IA), an anastomotic line was placed to invaginate the medial branch of the right portal vein and also placed behind the veins even at their roots. This technique puts all portal branches outside of the anastomosis, preventing cicatricial adhesion at the dissected area with the posterior wall of the veins. METHODS: The effect of IA was evaluated in terms of resolution of jaundice and long-term outcome compared with conventional anastomosis (CA). Group IA consisted of 20 patients and group CA of 18 patients. RESULTS: Patients in whom jaundice resolved included 19 (95%) in group IA and 11 (61%) in group CA (P < .05). Reoperation was needed in only one infant in group IA, and in six in CA (P < .05). In patients with reoperation in group CA, the portahepatis was found to be contracted with dense cicatricial tissues. The survival rates for patients with a native liver, calculated excluding those in whom the cause of death was not liver deterioration, was 87% for IA compared with 41% for CA (P < .05). Averaged biliary atresia prognostic index at the last follow-up evaluation was 20.2+/-24.5 for group IA and 62.6+/-29.8 for group CA (P < .001). CONCLUSION: The invaginating anastomosis in portoenterostomy promised a sustained bile drainage and improved long-term outcome by preventing cicatricial contraction of the portahepatis.
We describe a rare case of a celiomesenteric anomaly with concurrent aneurysm. The patient, a 53-year-old man, had no abdominal pain or discomfort. The presence of a celiac artery aneurysm was suspected on the basis of the results of abdominal computerized tomographic scanning and echo ultrasound scanning performed because of proteinuria. Intra-arterial digital subtraction angiographic results showed the anomaly and aneurysm. Because of the risk of rupture of the aneurysm, the lesion was repaired surgically, with the placement of an interpositional prosthetic graft. We found no previous reports of celiomesenteric anomaly with concurrent aneurysm repaired with prosthetic graft.
A new anthraquinone, 2-hydroxymethyl-10-hydroxy-1,4-anthraquinone (1), was isolated from Hedyotis herbacea along with three other known derivatives: 1,4-dihydroxy-2-hydroxymethylanthraquinone (2); 2, 3-dimethoxy-9-hydroxy-1,4-anthraquinone; and 1,4-dihydroxy-2, 3-dimethoxyanthraquinone. The structure of 1 was determined based on analysis of its spectroscopic data.
BACKGROUND: The aim of this study was to examine telomerase activity in affected and adjacent tissue in patients with oesophageal squamous cell carcinoma (SCC). METHODS: Telomerase activity was measured in oesophageal SCC cells, normal oesophageal culture cells, primary cancer tissues and adjacent normal tissues from patients with oesophageal SCC using a polymerase chain reaction-based assay. RESULTS: All oesophageal SCC cells had telomerase activity, whereas normal cultured cells showed no activity. All 57 cancer tissues showed telomerase activity compared with only five (10 per cent) of 50 normal tissues. Cancer cells infiltrating the vessels of mucosal or submucosal tissues in non-cancerous regions were detected in four of five telomerase-positive normal tissues, whereas such infiltration was detected in only three of 45 telomerase-negative normal tissues. CONCLUSION: In patients with oesophageal SCC, measurement of telomerase activity in normal epithelium is a highly sensitive method of detecting the microinvasion of cancer cells.
BACKGROUND: The efficacy of intraportal perfusion with prostaglandin E1(PGE1) in decreasing postischaemic hepatic microcirculatory damage was studied in rats. METHODS: An extrahepatic portosystemic shunt was created by attaching the spleen to a subcutaneous site on the left lateral wall of the abdomen in male Wistar rats weighing between 200 and 350 g. Four weeks later, when the shunt was mature, the portal vein and hepatic artery were occluded for 60 min. The animals were divided into the following three groups according to the type of intraportal perfusion during the ischaemic phase: group 1 consisted of untreated animals; group 2, animals perfused with lactated Ringer's solution; and group 3, animals perfused with PGE1 (0.1 microg/kg per min). The hepatic microcirculation was observed under an inverted intravital microscope after the injection of fluorescent dyes to label leucocytes and damaged cells 30 and 60 min after reperfusion. The liver was removed 60 min after reperfusion and stained immunohistochemically using 1A29, an anti-rat intercellular adhesion molecule-1 (ICAM-1) antibody. RESULTS: The leucocyte velocity during reperfusion was lowest in group 1 and highest in group 3. Of the three groups, group 3 showed the least leucocyte adhesion to the sinusoidal walls and terminal venules, the lowest damaged cell count and the lowest ICAM-1 expression on the sinusoidal walls. CONCLUSION: The results of this study suggest that hepatic perfusion with PGE1 markedly alleviates microcirculatory damage associated with ischaemia and reperfusion through the inhibition of leucocyte-endothelium interactions.
The degree of tumor malignancy generally correlates to tumor grade, and the direct measurement of tumor vasculature is desired. Dynamic susceptibility contrast magnetic resonance imaging can provide relative cerebral blood volume and, therefore, is one of the most reliable methods to evaluate tumor vasculature in vivo. Tumor vessel size is extremely variable due to complex tumor angiogenesis, and the gradient-echo echo-planar imaging (GE-EPI) technique, which is sensitive to the total vascular bed, is well suited for this purpose. As many studies have shown, dynamic susceptibility contrast magnetic resonance imaging is more useful for grading glioma than conventional magnetic resonance imaging. We found that this technique can also provide supplementary information to differentiate between malignant lymphoma and glioma because the absence of tumor neovascularization of malignant lymphoma leads to low rCBV, which is in contrast to those of malignant gliomas. Indeed, this technique can be used for the differentiation of extra-axial tumors such as between meningioma and neurinoma. Recently, this technique has been focused toward determining the stereotactic biopsy site, monitoring the embolization of effect in meningioma, or evaluation of treatment effects after radiation therapy. However, the value of tumor rCBV is affected by many conditions such as the T1 relaxivity effects of gadolinium in the extravascular space. To establish the usefulness of this technique, further examination will be needed.
R-94138, a matrix metalloproteinase inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK-1. When the supernatant of a co-culture of TMK-1 cells and human normal fibroblast cells was subjected to gelatin zymography, it was clear that the protein expression of MMP-2 had been inhibited by R-94138. When TMK-1 was injected intraperitoneally (i.p.) into nude mice at 5 x 10(5) cells/body, the resulting peritoneal dissemination mimicked clinical carcinomatous peritonitis. When the maximum tolerated dose of mitomycin C (MMC) or cisplatin (DDP) was given 12 h after the tumor inoculation, peritoneal dissemination was completely inhibited, while the effect of R-94138 was limited when it was given i.p. at a dose of 20 mg/kg in a schedule of q.d. x 5 starting 12 h after tumor injection. MMC and DDP also suppressed peritoneal dissemination when they were administered 1 week after the tumor inoculation at a single dose of 2 and 3 mg/kg i.p., respectively. R-94138 inhibited peritoneal dissemination when it was administered i.p. at a dose of 30 mg/kg in a schedule of q.d. x 5 starting from 1 week after tumor injection. The combination of MMC and R-94138 increased the preventive effect on peritoneal dissemination. R-94138 seems to be a promising candidate to prevent peritoneal dissemination of gastric cancer.
Pancreatic cancer is the disease of gastrointestinal cancer with the poorest prognosis. At present, in addition to surgery, multimodality treatment combining a variety of therapeutic methods is used. We usually employ the following combination of surgery, radiotherapy and chemotherapy: D2 surgery with pylorus-preserving pancreatoduodenectomy (PPPD), intraoperative radiotherapy (IORT), and portal catheterization (PC) with fluorouracil as the chemotherapy. In this study, we made a historical comparison of PPPD and PD and obtained the following findings: (1) PPPD allows almost the same extent of D2 dissection as conventional PD, and achieves radical treatment without any problems; (2) suppression of local recurrence by IORT cannot be expected from the results of the comparison between the four approaches, i.e. surgery alone, surgery + IORT, surgery + PC and surgery + IORT + PC, and (3) the rate of liver metastasis in patients treated by PC was significantly low.
PURPOSE: To identify features useful for differentiation between malignant and benign breast neoplasms using multivariate analysis of findings by MR imaging. MATERIAL AND METHODS: In a retrospective analysis, 61 patients with 64 breast masses underwent MR imaging and the time-signal intensity curves for precontrast dynamic postcontrast images were quantitatively analyzed. Statistical analysis was performed using a logistic regression model, which was prospectively tested in another 34 patients with suspected breast masses. RESULTS: Univariate analysis revealed that the reliable indicators for malignancy were first the appearance of the tumor border, followed by the washout ratio, internal architecture after contrast enhancement, and peak time. The factors significantly associated with malignancy were irregular tumor border, followed by washout ratio, internal architecture, and peak time. For differentiation between benignity and malignancy, the maximum cut-off point was to be found between 0.47 and 0.51. In a prospective application of this model, 91% of the lesions were accurately discriminated as benign or malignant lesions. CONCLUSION: Combination of contrast-enhanced dynamic and postcontrast-enhanced MR imaging provided accurate data for the diagnosis of malignant neoplasms of the breast. The model had an accuracy of 91% (sensitivity 90%, specificity 93%).
We investigated the correlation between tumor sensitivity to 5-fluorouracil (5-FU) and the enzymatic activity and mRNA levels of thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) using human tumor xenografts in nude mice. Three gastric carcinoma xenografts (SC-1-NU, St-4, and H-111), two colon carcinoma xenografts (Co-4 and Col-3-JCK), one pancreatic carcinoma xenograft (PAN-3-JCK), and one breast carcinoma xenograft (MX-1) were inoculated into nude mice. When the resultant tumors reached 100-300 mg, 5-FU was administered i.p. at a dose of 60 mg/kg in a schedule of three times every 4 days, and the antitumor activity of 5-FU was evaluated as the relative mean tumor weight in treated mice compared to control mice. Xenografts were also inoculated into untreated nude mice. When tumors weighed 200-300 mg, tumor tissues were resected for measurement of tumoral TS and DPD. TS and DPD activities were detected by the TS-binding assay and a radioenzymatic assay, respectively. mRNA levels were measured by semiquantitative reverse transcription-PCR, with glyceraldehyde-3-phosphate dehydrogenase coamplified as an internal standard. TS and DPD activities ranged from 84.7 to 775.5 fmol/mg protein and from not detectable to 79.7 pmol/min/mg protein, respectively. TS and DPD mRNA levels ranged from 0.51 to 9.90 and from not detectable to 0.93, respectively. The enzymatic activities of TS and DPD were correlated with observed mRNA levels. DPD levels were significantly correlated with 5-FU sensitivity, with high DPD activity and high DPD mRNA level resulting in low sensitivity to 5-FU. In contrast, no correlation between TS level and 5-FU sensitivity was observed. Tumoral DPD activity and DPD mRNA level may be useful indicators in predicting the antitumor activity of 5-FU.
Patients with Barrett's columnar-lined esophagus are at increased risk of developing esophageal adenocarcinoma, the incidence of which has increased rapidly especially in the USA. Although the number of patients with Barrett's adenocarcinoma is fewer in Japan than in the USA, all gastroenterologist should know its multistep carcinogenic process. Tumor suppressor genes (p53, p16), oncogenes (c-erbB-2, H-ras, K-ras, cyclin D1, src), and growth factor/receptor (TGF-alpha, EGFR) seem to cause the malignant transformation of Barrett's esophagus. Because detection of these molecular alterations is feasible, more accurate diagnosis of Barrett's esophageal biopsy specimens should be made by adding the molecular examination to the conventional pathologic examination.
Although endoscopic surgery has become widespread and is currently used in a wide range of general, thoracic, urologic, gynecologic, and orthopedic procedures, many major difficulties remain because sensorial information is restricted to a two-dimensional image, and effector instruments have limited maneuverability due to the rigid shaft axis fixed to the abdominal wall by the entry trocar. To overcome these problems, advanced engineering technology has been introduced in laparoscopic surgery which includes three-dimensional video imaging, robotic laparoscopic cameraholders, telemanipulated flexible effector instruments, and tactile feedback. A voice-controlled robotic laparoscopic holder (AESOP200, Computer Motion Inc. USA) provides stable support for the laparoscope during laparoscopic surgery performed by a single surgeon. A new computer-assisted telemanipulation robot (Intuitive Surgical Inc. USA) permits the performance of completely endoscopic coronary artery bypass and Nissen fundoplication. Furthermore, price reductions and technological advances in telecommunications have made telementoring in endoscopic surgery available for routine clinical use, and intercontinental surgical video teleconferences fruitful opportunities for discussing technical details. The fusion of medicine and technology in endoscopic surgery would overcome difficulties in the conventional endoscopic approach.
Ischemic colitis is the most common manifestation of gastrointestinal ischemia. The presumed etiologies are numerous; however, it typically develops spontaneously. It is classified into the transient type, stricture type, and gangrenous type. The majority of patients with ischemic colitis, excluding the gangrenous type, follow a benign clinical course in the absence of major vasculature occlusion. It usually presents as an acute abdominal illness with bloody diarrhea. Diagnosis is confirmed by colonoscopy and/or barium enema. Nongangrenous ischemic colitis usually requires only conservative therapy, including repeated careful assessment, pain control, and fluid replacement, and is associated with a good prognosis. It may lead to the sequela of persistent segmental colitis or colonic strictures, occasionally requiring surgery. Urgent surgery and high morbidity and mortality rates are hallmarks of the gangrenous type. Special consideration must be given to those patients in whom ischemic colitis develops in the context of colon cancer or obstructive colonic lesions. Successful management of a patient with ischemic colitis requires a high degree of clinical suspicion, early diagnosis, careful follow-up, and prompt recognition of persistent disease.
BACKGROUND: We evaluated the usefulness of preoperative dipyridamole myocardial scintigraphy (DMS) under low-level exercise in predicting postoperative cardiac problems in patients undergoing elective abdominal aortic aneurysm (AAA) repair. METHODS EXPERIMENTAL DESIGN: retrospective comparison of patients who did and did not undergo the investigation preoperatively. SETTING: at the Keio University Hospital and the Kawasaki City Hospital. PATIENTS: eighty-five patients who had abdominal aortic aneurysm repair consecutively from 1986 to 1990 without undergoing dipyridamole myocardial scintigraphy preoperatively were compared with 118 patients who underwent the repair consecutively from 1991 to 1997 after having had preoperative scintigraphy. MEASUREMENTS: postoperative occurrences of myocardial infarction and angina pectoris in the two groups of patients were compared statistically. RESULTS: In the group not having scintigraphy, cardiac events occurred in 12 patients (14.1%) after repair. Ten patients had a myocardial infarction; six died within 30 days of operation and four died after the 31st postoperative day. The other two patients had angina pectoris; both survived. In the group having scintigraphy, there were no postoperative cardiac events (p<0.001). Seventeen patients had positive results on preoperative scintigraphy. Seven of them had undergone coronary artery bypass grafting and five coronary angioplasty before the repair. In the five other patients, scintigraphy, was found to have yielded false positive results. CONCLUSIONS: Dypiridamole myocardial scintigraphy is an accurate predictor of postoperative myocardial infarction and angina pectoris in patients being evaluated for elective abdominal aortic aneurysm repair and should be used routinely.
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BACKGROUND AND PURPOSE: The T1-weighted fast spin-echo (T1-FSE) MR imaging sequence is not used routinely, since the speed advantage is not as dramatic as it is in T2-weighted imaging. We evaluated the T1-FSE sequence to determine whether this technique can replace the conventional T1-weighted spin-echo (T1-SE) sequence for routine contrast-enhanced imaging. METHODS: Sixty-nine patients with intracranial enhancing lesions underwent both T1-SE and T1-FSE sequences in a random order after administration of contrast agent. Acquisition time was 55 seconds for the T1-FSE sequence and 2 minutes 38 seconds for the SE sequence. The conspicuity of enhancing lesions, peritumoral edema, and gray-to-white matter contrast as well as motion and flow artifacts were analyzed. Signal-to-noise ratios of enhancing lesions, gray matter, and white matter as well as contrast-to-noise ratios (CNRs) of enhancing lesions, with gray matter with white matter as the standard, were calculated. RESULTS: The conspicuity of enhancing lesions was better on T1-FSE sequences than on T1-SE sequences, although the difference in the CNRs of enhancing lesions did not reach significance. Images obtained with the T1-FSE sequence showed less flow and motion artifacts than did those obtained with the T1-SE sequence. The conspicuity of peritumoral edema and gray-to-white matter contrast was lower on the T1-FSE images than on the T1-SE images. CONCLUSION: The T1-FSE sequence reduces imaging time and has the potential to replace the conventional T1-SE sequence for the evaluation of enhancing lesions in the brain when time is a consideration.