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Biomedical subjects

Masaki Kitajima

Publications and source records attributed to Masaki Kitajima.

At least 181 records · Page 10Linked to original sources

[Current status and future perspectives of sentinel node navigation surgery for esophageal cancer].

Esophageal cancer is a particularly aggressive malignancy because of the high incidence and widespread distribution of lymph node metastases. However, the sentinel node (SN) concept appears to be applicable even for esophageal cancer, according to recent reports. A dye-guided method is not applicable for esophageal cancer because of its anatomic site. It is impossible to trace the flow of blue dye within a certain observation time without destruction of the lymphatic network. SNs in esophageal cancer are multiple and their distribution is widely spread from the cervical to the abdominal area. Therefore the lymphoscintigram in the radio-guided method is essential to identify the SNs in esophageal cancer. Recently chemoradiotherapy has attracted attention as a multidisciplinary curative treatment for cT1N0 esophageal cancer. In this approach, control of invisible micrometases is essential. Lymphoscintigrams revealing the distribution of SNs in each individual case are useful to plan the field of irradiation. Selective and modified lymphadenectomy for clinical N0 esophageal cancer should become feasible and clinically useful. Individualized selective lymphadenectomy for cN0 esophageal cancer located in the esophagogastric junction including Barrett's carcinoma based on SN status would be a reasonable surgical approach.

Esophageal Neoplasms↗

A possible defensive mechanism in the basal region of gastric mucosa and the healing of erosions.

A possible defensive mechanism in the basal region of the gastric mucosa was hypothesized in the present study. In vivo microscopy was performed to observe the basal region after thermal injury to the back skin of rats. A donor of nitric oxide, 3-morpholinosydnonimine hydrochloride (SIN-1), or a serine protease inhibitor, camostat mesilate, was administered. Anti-vascular endothelial growth factor (VEGF) neutralizing antibody was administered 5 hours after thermal injury (anti-VEGF group). Post-capillary venules could be observed in the basal region of the gastric mucosa (PV-BGM). The PV-BGM was dilated 5 hours after thermal injury, and it was reduced by the administration of SIN-1 or pre-treatment with camostat mesilate. In the control group, the erosions did not reach the basal region of the gastric mucosa. Most of the erosions healed within 72 hours. Delayed healing was observed in the anti-VEGF group. In this group, exudation and congestion in the basal region were observed at 24 hours, and ulcer formation was observed at 72 hours after thermal injury. It is thus hypothesized that blood flow of the PV-BGM increases when superficial mucosal circulation is disturbed. The PV-BGM can contribute to defensive mechanisms in the basal region of gastric mucosa. The abnormal healing process may disturb the defensive mechanism at the base of the gastric mucosa, thereby resulting in ulcer formation.

Animals↗

Transfer of the interleukin-1 receptor antagonist gene into rat liver abrogates hepatic ischemia-reperfusion injury.

BACKGROUND: The anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) is known to reduce hepatic ischemia-reperfusion injury. Therefore, we wished to examine the effect of IL-1Ra gene delivery into the rat liver on hepatic ischemia-reperfusion injury. METHODS: IL-1Ra cDNA was delivered into the rat liver by a single injection of the transgene vector into the portal vein using either the plasmid-cationic liposome or the recombinant adenoviral vector. At 24 hours after the gene delivery, rats were subjected to partial liver ischemia for 90 minutes followed by reperfusion. Liver tissue and serum samples were taken at 180 minutes of reperfusion, and the degree of the liver injury as well as the expression level of pro-inflammatory cytokines in the serum and tissue were investigated. In addition, we assessed the effect of IL-1Ra gene delivery on the 7-day survival rate when the nonischemic liver lobe was partially excised immediately following reperfusion. RESULTS: In both cases of delivery methods, gene transfer of IL-1Ra resulted in significant elevation of serum IL-1Ra concentration, which reached maximal levels at 24 hours following the delivery. However, the highest serum concentration with the adenoviral vector was 1,000-fold of that in the liposome-treated animals. In the IL-1Ra delivered rats, liver damage, as well as production of pro-inflammatory cytokines, at 180 minutes of reperfusion was significantly reduced in a concentration-dependent manner of the circulating IL-1Ra protein. Rats subjected to the adenoviral vector gene delivery had higher 7-day survival rates compared with control animals. CONCLUSIONS: IL-1Ra gene delivery into the liver may be of therapeutic use for abrogating hepatic ischemia-reperfusion injury after transplantation.

Animals↗

B7/CTLA4 pathway is essential for generating regulatory cells after intratracheal delivery of alloantigen in mice.

BACKGROUND: The mechanism of hyporesponsiveness induced by intratracheal (IT) delivery of alloantigen was examined and its effect on cardiac graft survival was assessed in studies in mice. METHODS: In CBA (H2 ) mice, donor splenocytes were given by IT delivery 7 days before transplantation of a C57BL/10 (H2 ) heart. To determine whether regulatory cells were involved in hyporesponsiveness, splenocytes from mice given IT delivery of alloantigen and antibodies for B7-1, B7-2, or CTLA4 were adoptively transferred to naïve secondary recipients 7 days after delivery; those recipients underwent heart transplantation the same day. Effects on cell proliferation and cytokine production of splenocytes from mice given IT delivery of alloantigen were examined in mixed leukocyte cultures (MLC). RESULTS: Cardiac graft survival was significantly prolonged in mice given IT delivery of alloantigen (median survival time [MST], 81 days); those given syngeneic splenocytes rejected grafts acutely (MST, 7 days; P<0.05). Adoptive transfer of splenocytes also significantly prolonged survival of cardiac grafts in secondary recipients (MST, 62 days). When B7-1, B7-2, or CTLA4 antibody was combined with IT delivery of alloantigen in the first recipient, all grafts were rejected within 14 days in second recipients after adoptive transfer. In mixed leukocyte cultures, splenocytes from these mice did not respond to alloantigen and production of interleukin-4 and interleukin-10 was increased. CONCLUSIONS: Donor splenocytes delivered IT induced hyporesponsiveness and regulatory cells in our animal model, and such induction was dependent on B7-1, B7-2, and CTLA4 signals.

Abatacept↗

Intraportal infusion therapy as a novel approach to adult ABO-incompatible liver transplantation.

BACKGROUND: ABO-incompatible liver transplantation is associated with an extremely complicated postoperative course, especially when the recipients are adults. METHODS: Two adult patients underwent living-donor liver transplantation from ABO-incompatible donors. The antirejection therapy included multiple perioperative plasmapheresis, splenectomy, systemic triple immunosuppressive regimen with tacrolimus, methylprednisolone, and cyclophophamide, or azathioprine. In addition to these conventional approaches, we performed intraportal infusion therapy after transplantation with methylprednisolone, prostaglandin E1, and gabexate mesilate. RESULTS: With our protocol, antidonor blood group antibody titers in both cases remained low without any evidence of rejection or vascular complications throughout the postoperative course. Biliary complications were transient and resolved completely. The patients have now survived 30 and 12 months posttransplantation and have regained normal life activity with good liver function. CONCLUSIONS: Our experience has shown the feasibility of controlling rejection and other complications in adult ABO-incompatible liver transplantation under intraportal infusion therapy.

ABO Blood-Group System↗

One-stage surgical management of concomitant abdominal aortic aneurysm and gastric or colorectal cancer.

One-stage surgical management of concomitant abdominal aortic aneurysm (AAA) and gastric or colorectal cancer should provide certain benefits. We reviewed the records of 21 patients with both AAA and gastric or colorectal cancer who underwent one-stage surgical management. Four had distal gastrectomy, 2 had total gastrectomy, and 5 had abdominoperineal rectal resection transperitoneally; 3 had total gastrectomy transperitoneally and AAA repair extraperitoneally. Two underwent right hemicolectomy and thromboexclusion of the AAA. Two had creation of a temporary ileostomy and implantation of an interposition graft. Two underwent left hemicolectomy, creation of a temporary transversostomy, and implantation of an interposition graft. One had a Hartmann's procedure and implantation of a bifurcated prosthetic interposition graft for AAA. There were no operative deaths or serious postoperative complications. One patient had colorectal ischemia that resolved with conservative treatment. Eighteen of the 21 patients (85.7%) were alive 10 months to 14 years postoperatively. In conclusion, one-stage surgical treatment of concomitant AAA and gastric or colorectal cancer is well tolerated and can avoid the time, financial costs, and patient anxiety involved in a second operation.

Aged↗

Significance of transforming growth factor beta1 as a new tumor marker for colorectal cancer.

Transforming growth factor beta1 (TGF-beta1) is thought to be involved in cancer growth and progression. TGF-beta1 changes to its active form after being secreted in its latent form. Our aim was to clarify the significance of plasma concentrations of active and total TGF-beta1 of patients with colorectal cancer. Plasma concentrations of active and total TGF-beta1 in 45 patients with colorectal cancer and 23 healthy volunteers were measured using ELISA and the activation rate (ratio of active to total TGF-beta1) was determined. Plasma concentrations of active TGF-beta1 (21.9 +/- 12.8 pg/ml) were significantly higher in patients with colorectal cancer than in healthy volunteers (9.9 +/- 5.9 pg/ml; p < 0.001, Welch's t-test). Concentration of total TGF-beta1 was also significantly higher for patients with colorectal cancer (18.0 +/- 13.0 ng/ml vs. 11.1 +/- 6.4 ng/ml; p < 0.01, Welch's t-test). However, there was no significant difference in the TGF-beta1 activation rate between the 2 groups. There was a correlation between Dukes' stage and plasma concentration of active or total TGF-beta1 (p < 0.01, Spearman's rank correlation test) and on day 7 the active TGF-beta1 levels for patients recovering from curative resection were similar to those of the control group of healthy volunteers. These results suggest that active TGF-beta1 might be used as a tumor marker for colorectal cancer.

Adenocarcinoma↗

Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences.

Restriction landmark genomic scanning (RLGS) was utilized to identify novel genomic alterations in hepatocellular carcinoma (HCC). Thirty-one HCC samples were examined by RLGS. Two high intensity spots were common to several RLGS profiles of different HCCs. Nucleotide sequencing and homology search analysis showed that these spots represented repetitive sequences, Human tandem repeat sequence (Genbank, L09552) and centromeric NotI cluster (Genbank, Y10752). These intensified signals were attributable to the occurrence of demethylated areas in the recognition sequence of the NotI site of the corresponding fragments. The intensity of these spots in the RLGS profile reflects their degree of demethylation, which was significantly correlated with postoperative recurrence, even in patients regarded as belonging to the good prognosis group by conventional prognostic factors. Multivariate analysis showed that the intensities of the two spots retained independent prognostic value. This is a new type of predictive factor for HCC based on epigenetic changes in hepatocarcinogenesis, and in the future it is expected to be of great value in making preoperative diagnosis and selecting postoperative therapy.

Adult↗

Gastrointestinal cancer and sentinel node navigation surgery.

In the twentieth century, lymph node dissection based on metastatic distribution has developed as the standard procedure for surgical management of gastrointestinal cancer [1]. The fear that invisible micrometastases might be present has encouraged aggressive resection with lymphadenectomy to control the disease. However, the prognostic benefits of extensive surgery are still unknown and the universal application of radical surgery may affect surgical morbidity, mortality, and quality of life after surgery, particularly in patients without lymphatic spread. In the twenty-first century, a novel technology to detect micrometastases without extensive surgical resection is required to establish an individualized surgical management approach to gastrointestinal cancer. Lymphatic mapping techniques are now used in the control of superficial malignancies, such as malignant melanoma and breast cancer, providing a novel tool that may also be of use for gastrointestinal cancers.

Esophageal Neoplasms↗

The role of neoadjuvant chemotherapy for breast cancer treatment.

Neoadjuvant chemotherapy has become popular, especially for patients with advanced breast cancer. The pros and cons of neoadjuvant chemotherapy for treating breast cancer patients are reviewed. The advantages of neoadjuvant chemotherapy are 1) overall survival and recurrence-free survival rate are the same as post-operative chemotherapy, 2) serves as an in vivo sensitivity test, 3) increases the rate of breast conserving therapy, 4) facilitates the study of cancer biology. On the other hand, the disadvantages of neoadjuvant chemotherapy are 1) it modifies the stage, 2) treatment delay of PD cases, 3) residual intraductal component may be left behind after breast conserving surgery, 4) there are some cases of over-treatment. Combination chemotherapy is one possible way to increase the pathological CR rate, although the optimal order and cycles have not been determined. To avoid residual cancer cells after breast conserving surgery, the shrinkage pattern should be evaluated by MRI. Core needle biopsy should be performed before neoadjuvant chemotherapy to avoid over-treatment. It is essential to develop more effective regimens and stratify patients based on predictive factors.

Antineoplastic Agents↗

UCN-01 (7-hydroxystaurosporine) inhibits the growth of human breast cancer xenografts through disruption of signal transduction.

BACKGROUND: 7-Hydroxystaurosporine (UCN-01), originally isolated as a phospholipid-dependent protein kinase C inhibitor, has been shown to have antitumor activity against several human cancer cell lines. UCN-01 inhibits cell cycle progression from the G1 to S phase by inhibition of cyclin-dependent kinase (CDK) activity and induction of intrinsic CDK inhibitor protein, leading to dephosphorylation of retinoblastoma (Rb) protein. MATERIALS AND METHODS: The antitumor activity of UCN-01 has been investigated against three human breast carcinoma strains serially transplanted into nude mice, including estrogen-dependent MCF-7, Br-10, and estrogen-independent MX-1. When the inoculated tumors started growing exponentially, UCN-01 (7.5 mg/kg) was administered intraperitoneally on five consecutive days a week for 2 weeks. The antitumor effect was evaluated as the lowest T/C ratio (%) during the experiments, where T was the relative mean tumor weight of the treated group and C was that of the control group. At the end of UCN-01 administration expression of p21, a protein of the CDK inhibitor family, and phosphorylated and dephosphorylated Rb protein was detected by Western blotting using treated and control tumors. RESULTS: UCN-01 had activity against MCF-7 and Br-10, with the lowest T/C ratios of 25.0% and 27.0%, respectively, while MX-1 was resistant to UCN-01 with a T/C ratio of 65.9%. The antitumor spectrum of UCN-01 was different from that of other conventional agents such as doxorubicin and cyclophosphamide which were ineffective against Br-10 but were active against MX-1. Although p21 was induced in three tested strains by UCN-01, little dephosphorylated Rb protein was expressed in MX-1 compared with Br-10 and MCF-7 (in vitro). CONCLUSION: UCN-01 appeared to be a promising agent for the treatment of breast cancer, with a different mode of action and antitumor spectrum from other currently available antitumor drugs.

Alkaloids↗

Serrated adenoma developing into advanced colon cancer in 2 years.

We report the case of a 76-year-old woman with a flat elevated lesion (laterally spreading tumor; LST) in the transverse colon that had been identified 2 years before the current presentation. Pathologically, the lesion had been diagnosed as a serrated adenoma with severe dysplasia. The patient had refused endoscopic resection because she was afraid of the risk of colonic perforation; she did not come to follow-up until 2 years after the diagnosis, when she had advanced colon cancer in the transverse colon where the LST had been detected. Histopathological examination confirmed a poorly differentiated adenocarcinoma with no adenomatous component such as had been found in the LST lesion.

Adenocarcinoma↗

Rare case of early mucosal gastric cancer presenting with metastasis to the bulbar conjunctiva.

Early gastric cancer has an excellent outcome following surgical treatment. In particular, mucosal gastric cancer (m-cancer) very rarely results in metastatic dissemination and may be successfully treated by local surgical resection. We report a 64-year-old Japanese woman who presented with a recurrent cystic lesion on the left bulbar conjunctiva, with a biopsy specimen revealing metastatic signet-ring cell carcinoma. Gastrointestinal investigations revealed an early gastric cancer in the lesser curvature of the stomach. Biopsy specimen of the gastric lesion indicated poorly differentiated adenocarcinoma, which was identical to findings in the lesion in the bulbar conjunctiva. She underwent a distal gastrectomy and made an uneventful recovery. Histopathological analysis indicated a gastric signet-ring cell carcinoma that was limited to the mucosal layer, without evidence of lymphatic spread. Although the exact mechanism of metastatic dissemination to the bulbar conjunctiva is unclear, this case is very unusual, because ocular metastases almost invariably occur in the context of documented and established malignant disease. This is, to our knowledge, the first reported case of a patient with gastric mucosal cancer who presented with a conjunctival metastatic deposit and who subsequently received curative surgical treatment for both conditions.

Adenocarcinoma↗

Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer.

PURPOSE: Epidemiologic studies indicate that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies demonstrate increased expression of cyclooxygenase-2 in human colorectal cancer tissues. However, the role of cyclooxygenase-2 expression in colorectal cancer has not yet been fully established. The aim of this study was to clarify the clinicopathologic significance of cyclooxygenase-2 expression in human colorectal cancer. METHODS: A total of 232 surgically resected colorectal cancer specimens were analyzed immunohistochemically with the use of a murine anti-human cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was then compared with clinicopathologic background and survival outcome. RESULTS: Cyclooxygenase-2 was expressed in the cytoplasm of the cancer cells but not in normal epithelium. Cyclooxygenase-2 expression was noted in 71.6 percent (166/232) of the cancer patients and correlated significantly with histologic type (P = 0.033), depth of invasion (P = 0.016), pathologic stage (P = 0.020), and metachronous liver metastasis (P = 0.001). Multivariate analysis for factors associated with metachronous liver metastasis showed that cyclooxygenase-2 expression was one of the independent risk factors, second only to lymph node metastasis. Patients with cyclooxygenase-2 expression showed a significantly poorer outcome compared with those without cyclooxygenase-2 expression (P = 0.002). CONCLUSION: Cyclooxygenase-2 expression in the primary lesion may be a useful marker for evaluating prognosis and liver metastasis in patients with colorectal cancer.

Aged↗

Successful application of laparoscopic surgery to the treatment of Crohn's disease with fistulas.

PURPOSE: The role of laparoscopic surgery in patients with Crohn's disease remains to be defined, although increasingly difficult cases are being treated using minimally invasive techniques. We examined technical feasibility in 20 patients with Crohn's disease associated with fistulas. METHODS: Laparoscopic surgery was attempted in 37 patients with stricturing ileal disease or ileocolonic Crohn's disease from 1994 to 2000 after failure of strict nutritional therapy. Twenty of these patients with a total of 31 intestinal fistulas (14 ileoileal, 6 ileocolonic, 5 ileorectal, 2 ileovesical, 2 ileocutaneous, 1 gastrocolic, and 1 ileoduodenal) underwent 25 operations. Fistulas were divided intracorporeally, except for ileoileal fistulas. Fifteen patients underwent ileocecal resection; six underwent strictureplasty; six underwent partial resection of the small intestine; three underwent segmental colonic resection; and one underwent resection of anastomotic recurrence. Median follow-up was 48 (range, 5-77) months. RESULTS: Oral intake was started a median of 1 (range, 1-9) day after operation, and patients were discharged a median of 8 (range, 6-21) days after surgery. Four complications were observed in 25 operations (16 percent), including 1 intestinal obstruction/ileus, 2 wound infections, and 1 intra-abdominal abscess. There were no intraoperative or postoperative deaths. Four of the 5 operations were converted to open surgery (16 percent). Three of the 5 patients (60 percent) who required reoperation for anastomotic recurrence underwent repeated laparoscopic surgery using the same small incision. CONCLUSION: Laparoscopic treatment for Crohn's disease complicated by fistulas is feasible without high complication or conversion rates. Recurrent disease requiring reoperation can also be successfully treated using laparoscopic methods.

Adult↗