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Yuko Kitagawa

Publications and source records attributed to Yuko Kitagawa.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Recent studies of sentinel lymph node. Multicenter prospective clinical trials of SN biopsy for gastric cancer].

The sentinel node (SN) is defined as the first draining node from the primary lesion, and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. Recently, the validity of the SN concept in gastric cancer has been demonstrated by a number of single institutional studies, and prospective multi-center trials are presently ongoing. The Gastric Cancer Surgical Study Group of the Japan Clinical Oncology Group (JCOG) organized a multi-center prospective study of SN mapping by the dye-guided method using subserosal injection of indocyanine green. If the JCOG study reveals favorable results, in terms of false-negative rates, the dye-guided method will be utilized as a routine practice for open surgery in a wide range of institutions. If not, we will need to consider introduction of radioguided method or add further technical improvements, even for open surgery. A study group in the Japan Society of Sentinel Node Navigation Surgery is also conducting a multi-center prospective trial of SN mapping by a dual tracer method with blue dye and radio-active colloid. Even if the SNNS study demonstrates acceptable detection rates and low false-negative rates, we need to conduct a feasibility study of laparoscopic SN mapping for gastric cancer as the next step. The results of these clinical trials should provide useful perspectives on the future direction of SN navigation surgery for gastric cancer.

Clinical Trials as Topic↗
PubMed2005

Expression of basic fibroblast growth factor is associated with a good outcome in patients with squamous cell carcinoma of the esophagus.

Angiogenesis is an essential step in tumor growth and metastasis, but rather than being controlled by means of a simple mechanism, the control of tumor angiogenesis may be mediated by several angiogenic factors. We investigated the expression of basic fibroblast growth factor (b-FGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in squamous cell carcinoma of the esophagus in order to clarify the mechanism of angiogenesis. Expression of b-FGF and PD-ECGF was immunohistochemically investigated in tissue specimens from the tumors of 79 patients with squamous cell carcinoma of the esophagus who underwent curative esophagectomy without preoperative chemotherapy or radiation therapy, and the relationship between expression of b-FGF/PD-ECGF, microvessel density (MVD), and clinicopathological background factors was assessed. Tumor cells that expressed b-FGF were found in 41 patients (51.9%), and tumor cells that expressed PD-ECGF were found in 57 patients (72.2%). Although the mean vascular density (47.9/mm(2)) of b-FGF-positive tumors was significantly lower than that (67.2/mm(2)) of b-FGF-negative tumors (p=0.014), the difference between the 56.0/mm2 in PD-ECGF-positive tumors and 60.3/mm2 in PD-ECGF-negative tumors was not significant. Although the survival rate of patients with b-FGF-positive tumors was significantly higher than those with b-FGF-negative tumors (p=0.033), there was no significant difference between the survival rates of patients with PD-ECGF-positive and -negative tumors (p=0.580). Expression of b-FGF may be associated with promotion of angiogenesis and a good prognostic factor in squamous cell carcinoma of the esophagus.

Adult↗
PubMed2004

Loss of p16INK4a expression is associated with vascular endothelial growth factor expression in squamous cell carcinoma of the esophagus.

Vascular endothelial growth factor (VEGF) expression has been suggested to correlate with intratumoral microvessel density, tumor advancement and prognosis in esophageal squamous cell carcinoma (ESCC). Previous studies have showed that disruption of cell cycle regulator p16 is related to oncogenesis and tumor progression in ESCC. We hypothesized that VEGF expression in ESCC is reflected by abnormalities in the p16(INK4a) gene. To clarify the regulatory role of p16(INK4a) in VEGF expression in vitro, we transferred the p16(INK4a) gene into a p16(INK4a)-deleted ESCC cell line and observed changes in VEGF expression. Furthermore, we immunohistochemically assessed the expression of the cell cycle regulators (p16, p53 and RB) and VEGF in 90 surgically resected specimens of ESCC. Introduction of p16(INK4a) cDNA by the p16 expression vector significantly suppressed cell proliferation in the p16(INK4a)-deleted cell line TE8 (p < 0.0001). VEGF secretion by TE8 cells transfected with the p16(INK4a) vector was significantly suppressed as compared to non-transfected TE8 cells (p < 0.0001) and TE8 cells transfected with a control vector (p = 0.0015). The immunohistochemical studies of ESCC primary tumor specimens showed that loss of p16 expression was significantly correlated with VEGF-positive expression (p = 0.0004). The cumulative postoperative survival rate in the group with p16-positive and VEGF-negative expression was significantly higher than in the other groups. Neither p53 nor RB expression had any impact on outcome. Aberrant p53 expression tended to be associated with VEGF expression, but the trend did not reach statistical significance. Our study demonstrated that VEGF expression was correlated with p16 expression in ESCC. Our results suggest that p16 may have a regulatory role in VEGF expression in ESCC.

Aged↗
PubMed2004

Universal applications of sentinel node technology.

The sentinel node (SN) concept was originally proposed by several pioneers in the middle of the last century. After Donald Morton and his colleagues demonstrated the clinical significance of the SN concept in melanoma, it attracted vast attention in surgical oncology. At recent international conferences, a number of new approaches in this field for various solid tumors have been reported. Now, there are several possible applications with different technological aspects, such as individualized surgical management of solid tumors, multidisciplinary treatments, and novel therapeutic approaches. This article provides an overview of the future potential of SN technology.

Humans↗
PubMed2004

Current status and future prospects of sentinel node navigational surgery for gastrointestinal cancers.

Until the late 1990s, the application of the sentinel node (SN) concept to gastrointestinal (GI) malignancies was not recognized because of the multidirectional and complicated lymphatic flow from the GI tract. However, several studies supporting the validity of the SN concept for GI cancers have been reported in the past 5 years. Because of its anatomical location, gastric cancer is one of the most suitable targets for minimally invasive surgery based on SN status. Laparoscopic local resection is theoretically feasible for curative treatment of SN-negative early gastric cancer. Although SNs in esophageal cancer are multiple and are distributed widely from the cervical to the abdominal area, selective and modified lymphadenectomy for clinically N0-stage esophageal cancer is likely to become feasible and clinically viable. Total mesorectal excision (TME) is accepted as a standard surgical procedure for rectal cancer. However, there is a risk of aberrant distribution of SNs beyond the extent of TME; for example, SNs may be lateral to the lower rectum. SN mapping with scintigraphy is useful for effective sampling of SNs in unexpected areas and accurate staging without extensive lymph node dissection. There are several practical issues to be overcome. The techniques and feasibility of laparoscopic SN sampling are still under investigation. Large-scale multicenter prospective validation studies for SN mapping in GI cancer are essential. If these remaining issues can be solved, SN mapping for GI cancer will have great clinical impact.

Biliary Tract Neoplasms↗
PubMed2004

Historical review of lymphatic mapping in gastrointestinal malignancies.

The advent of sentinel lymph node mapping (SLNM) has had a profound impact on the surgical management of breast cancer and melanoma over the past decade. However, SLNM in gastrointestinal malignancies is still in its infancy. The role of SLNM in gastrointestinal malignancies is to increase staging accuracy and to reduce the understaging associated with standard surgical and pathological techniques. Numerous authors have described the successful use of SLNM in colon, rectal, gastric, esophageal, and anal canal malignancies, with a high degree of accuracy and upstaging by detailed pathological analysis of the sentinel nodes. Over the past 2 years, research and publications related to gastrointestinal lymphatic mapping have dramatically increased worldwide.

Colorectal Neoplasms↗
PubMed2004

Significance of metastasis detected by molecular techniques in sentinel nodes of patients with gastrointestinal cancer.

The clinical significance of micrometastasis in sentinel nodes (SNs) may differ in various organs. In particular, the prognostic value of SN micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) is still controversial. We investigated the diagnostic and therapeutic significance of nodal molecular metastasis detected by nested RT-PCR for cytokeratin (CK) 19 mRNA in gastrointestinal cancer. In 51 cases with GI tract cancer treated by standard curative resection, SNs were identified by a radio-guided method. In 10 of 51 patients, 25 SNs and 3 non-SNs were histologically negative and RT-PCR positive. Three non-SNs with positive CK19 mRNA were randomly sampled from the same basin where histologically positive SNs were identified. Immunohistochemical analysis of six additional step sections obtained at 30- micro m intervals with use of an anticytokeratin antibody showed clearly recognizable histological metastases in 4 of 25 histologically negative/RT-PCR-positive SNs (16%). In one case of esophageal squamous cell carcinoma with nodal micrometastasis identified by CK19 RT-PCR, extranodal local recurrence in the SN basin (left supraclavicular basin) was observed 6 months postoperatively. These findings suggest that nodal micrometastasis detected by nested RT-PCR has some clinical significance in GI cancer. Molecular assessment of the SN may be a valuable tool to complement routine histological examination for GI cancers.

Esophageal Neoplasms↗
PubMed2004

Lymphoscintigraphy for the visualization of sentinel lymph nodes and body contour.

BACKGROUND: It is important to create clear lymphoscintigraphic images when assessing the sentinel lymph nodes. This clarity needs to reach a level where the sentinel lymph nodes (SLNs) and the body contour are clearly visible. We have developed a simple image processing method using the division of primary and scattered photon counts. METHODS: Twenty patients with breast cancer were enrolled in this study. Manual injection of 150 MBq of Tc-99m tin colloid with small particle size into the peritumoral and subdermal regions was performed. Lymphoscintigraphy using a conventional gamma camera was performed three hours after the injection. Dual energy windows were set from 130 to 150 keV for the primary photons and 70 to 110 keV for the scattered photons. An anterior view of the chest and a lateral view from the affected side were obtained. Primary photon image counts were divided by the scattered photon image counts for each pixel after the addition of some constant counts to each pixel of the acquired image to improve the contrast of the scintigrams. We evaluated the ability to accurately visualize the body contour and the SLNs on the processed image. RESULTS: Image processing time was 20 to 40 seconds for each patient. In every case, the processed image clearly identified the body contour. The processed images allowed the identification of the same number of SLNs as the original images. CONCLUSIONS: This proposed method for image processing is a simple and useful means to clearly visualize both SLNs and body contours.

Adult↗
PubMed2004

Sentinel nodes of malignancies originating in the alimentary tract.

The feasibility of the sentinel node concept for malignancies originating in the alimentary tract is attracting much interest among researchers in the field of gastrointestinal oncology. We have tested more than 350 such cases and obtained favorable and promising initial results. The detectability of sentinel nodes using endoscopically injected Tc-99m tin colloid for these tumors exceeded 90%. Although the false negative ratio was not so low (approximately 10%), most of these cases had an inaccurate preoperative evaluation of mural invasion and/or a technically unfavorable injection. When the indication is restricted to patients with early-stage disease, and when the radioactive colloid is properly administered, sentinel node navigation therapy would be applicable for gastrointestinal malignancies. To achieve successful sentinel node navigation surgery it is essential to accurately identify sentinel nodes, and lymphoscintigraphy is a very useful test to confirm the location of sentinel nodes preoperatively. However, image processing is required for lymphoscintigrams because the original image depicts only high activity at the injection site and faint radioactivity in the sentinel nodes. We have clearly imaged the silhouette of the body using Compton scattered photons, and have also proposed several methods to improve the contrast between the injection sites and sentinel nodes. Many sentinel nodes can be clearly visualized by subtraction of the background activity with heterogeneous distribution. The development of the portable gamma camera, enabling intraoperative imaging, also contributes to less invasive biopsy of sentinel nodes. We have obtained promising initial results using a portable imaging device with semiconductor detectors. These promising results suggest that sentinel node navigation therapy including radiotherapy will be a new therapy for early-stage gastrointestinal malignancies in the near future, with nuclear medicine contributing to the establishment of new, less invasive therapies for gastrointestinal cancer.

Colorectal Neoplasms↗
PubMed2004

Metachronous gastric carcinoma from a gastric tube after radical surgery for esophageal carcinoma.

BACKGROUND: Cases of metachronous gastric carcinoma arising from a gastric tube used for reconstruction have been increasing in long-term survivors of esophageal cancer in recent years. We investigated the characteristics of gastric tube carcinoma to determine the most appropriate approach to managing it. METHODS: Between 1980 and 1997, 508 patients underwent radical esophagectomy for esophageal carcinoma at Keio University Hospital. Reconstruction was performed with a gastric tube in 414 (81.5%) of them, and 8 of them developed a metachronous carcinoma in the gastric tube. The clinical and pathologic characteristics of the gastric tube carcinomas were evaluated in this study. RESULTS: Gastric cancer was detected during follow-up endoscopic examinations or in an upper gastrointestinal series in seven patients. All of the cancers were diagnosed as adenocarcinoma histopathologically. Endoscopic mucosal resection was performed in two patients, partial resection of the residual stomach was performed in three patients. One patient was treated by endoscopic mucosal resection as palliative therapy, since he had severe pulmonary emphysema. Total resection of the gastric tube was attempted in 2 advanced cases but was unsuccessful because of direct invasion of other organ by the cancer. The 5 patients who underwent curative resection are alive with no subsequent recurrence. CONCLUSIONS: Since early diagnosis permits less invasive treatment and curative treatment is difficult in advanced cases, strict postoperative examinations are important after radical esophagectomy to ensure early detection of metachronous gastric carcinoma arising from gastric tubes used for reconstruction.

Adenocarcinoma↗
PubMed2004

Lymphatic mapping for upper gastrointestinal malignancies.

Recent studies on lymphatic mapping of upper gastrointestinal (GI) malignancies have provided new insights with regard to the sentinel node (SN) concept in solid tumors. At present, the SN concept seems to be valid not only for breast cancer, but also for esophageal and gastric cancers, which have multidirectional and complicated lymphatic flows. In addition to the staging merits, individualized surgical management has been proposed for upper GI cancer based on the SN concept. Gastric cancer is now a suitable target of SN-guided surgery after breast cancer because of its anatomical situation. Laparoscopic local resection is theoretically feasible for curative treatment of SN-negative early gastric cancer. Because SNs in esophageal cancer are multiple and widespread, complete sampling of SNs is not a minimally invasive procedure, as it is in breast cancer. However, selective and modified lymphadenectomy targeting SNs for clinically N0 esophageal cancer instead of three-field lymph node dissection should become not only feasible but also clinically important. When performing chemoradiotherapy as curative treatment for cT1N0 esophageal cancer, lymphoscintigrams revealing the distribution of SNs in each individual case are useful to tailor the field of irradiation to control occult micrometastases. Although there are several issues to be resolved, this novel procedure has the potential to improve quality control in upper GI cancer.

Esophageal Neoplasms↗
PubMed2003

Cell-cycle regulators and the Ki-67 labeling index can predict the response to chemoradiotherapy and the survival of patients with locally advanced squamous cell carcinoma of the esophagus.

BACKGROUND: We investigated whether aberrant p53 and p16 expression, the Ki-67 labeling index (LI), and int-2/cyclin D1 gene amplification predict the response to chemoradiotherapy (CRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: p53 and p16 expression status, the Ki-67 LI, and int-2/cyclin D1 amplification were assessed by immunohistochemical staining and slot blot analysis in pretreatment endoscopic biopsy specimens of 41 patients with T4 or M1 Lym (distant lymph node metastasis) ESCC. All patients received a course of chemotherapy (5-fluorouracil and cisplatin) with radiotherapy. RESULTS: The CRT therapeutic response rate was 71%, and resection after CRT was successful in 15 of the cases in which the CRT effect was significant. The cumulative survival rate after CRT in the p53-negative patients was significantly higher than in the p53-positive patients (P =.037). The mean Ki-67 LI in the CRT response cases was significantly higher than in the CRT no-response cases (P =.023). Multivariate regression analysis revealed high Ki-67 LI to be an independent variable linked to a pathologic complete response to CRT (P =.033). The cumulative survival rate after CRT in the group that was p53-negative and int-2/cyclin D1 amplification-positive was significantly higher than in the other groups (P =.008). CONCLUSIONS: Evaluating predictive factors in pretreatment endoscopic biopsy specimens may allow selection of more suitable multimodal treatment for ESCC patients and improve their quality of life.

Adenocarcinoma↗
PubMed2003

[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↗