Surgical treatment of esophageal cancer--the advent of the era of individualization.
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Adenocarcinoma↗
Biomedical subjects
Yuko Kitagawa
Publications and source records attributed to Yuko Kitagawa.
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↗
Meeting report of the 74th Congress of the Japanese Gastric Cancer Association.
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Humans↗
Sentinel node mapping for colorectal cancer with radioactive tracer.
PURPOSE: The aim of this study was to test the feasibility and accuracy of radioactivity-guided mapping of the first lymph nodes found in draining the primary tumor site for colorectal cancer. METHODS: We enrolled 56 consecutive patients with preoperative diagnosis of curatively resectable colorectal cancer. Endoscopic injection of technetium Tc 99m-labeled tin colloid (15 MBq) was performed preoperatively, and radioactive sentinel nodes were identified intraoperatively with a gamma probe. Standard radical resection with lymph node dissection was performed in all patients, and all resected nodes were evaluated by routine histopathologic examination. RESULTS: Radioactivity-guided methods were used to detect sentinel nodes in 51 (91 percent) of 56 patients. The number of lymph nodes resected was 23.9 +/- 15.2 per case. The number of sentinel nodes was 3.5 +/- 2.1 (range, 0-8) per case. In 18 of 22 patients with lymph node metastasis, the sentinel node was positive. The incidence of metastasis in the sentinel node (22 percent) was significantly higher than that in nonsentinel nodes (3 percent, P < 0.01). Diagnostic accuracy according to sentinel node status was 92 percent (47/51). Four false-negative cases in this study were advanced cases with T3 primary tumors. The detection rate and diagnostic accuracy for patients with T1 or T2 primary tumors (29 cases) were 100 percent each. CONCLUSION: Intraoperative radioactivity-guided sentinel node mapping was accurate for patients with colorectal cancer with T1 or T2 tumors. The results suggest that sentinel node mapping and intraoperative biopsy may be a sensitive and specific diagnostic method for detecting metastasis in regional lymph nodes in patients with colorectal cancer.
Adult↗
Clinical significance of telomerase activity in peripheral blood of patients with esophageal squamous cell carcinoma.
BACKGROUND: The presence of tumor cells in the blood stream is considered evidence of a high risk of distant organ metastasis. We examined the usefulness of telomerase activity in peripheral blood polymorphonuclear cells as an indicator of distant metastasis in patients with esophageal squamous cell carcinoma. METHODS: Telomerase activity was measured in the peripheral blood mononuclear cell and polymorphonuclear cell fractions obtained from blood samples of healthy volunteers mixed with squamous cell carcinoma cell lines, and cell distribution was analyzed by flow cytometry. Then telomerase activity of forty-two polymorphonuclear cell fractions obtained from esophageal squamous cell carcinoma patients was measured. RESULTS: Telomerase activity was detected in polymorphonuclear cell fractions and cell distribution analysis revealed the presence of esophageal squamous cell carcinoma cells. Organ metastasis was detected in 7 (78%) of the 9 patients with telomerase-positive polymorphonuclear cell fractions as opposed to only five (15%) of the 33 with telomerase-negative cases, and there was a significant positive correlation between telomerase activity and organ metastasis (p < 0.0008). CONCLUSIONS: Measurement of telomerase activity in the polymorphonuclear cell fractions is useful for identifying a high risk group for distant organ metastasis in patients with esophageal squamous cell carcinoma.
Aged↗
Sentinel lymph node biopsy in breast cancer using technetium-99m tin colloids of different sizes.
Axillary lymph node dissection (ALND) in the treatment of breast cancer is essential for predicting the prognosis and regional control of the tumor. At the same time ALND is associated with pain, numbness and sometimes lymphedema. Sentinel lymph node biopsy (SLNB) is a potential alternative procedure to conventional ALND in clinically node-negative breast cancer. In this study, we prepared the technetium-99m-labeled tin colloids with different sizes and compared their efficacy in SLNB. From September 1998 to February 2002, 184 clinically node-negative breast cancer patients were enrolled in the study at Keio University Hospital. Sentinel lymph nodes (SLNs) were identified by both blue dye and radioisotope. We prepared small-sized technetium-99m-labeled tin colloid (particle size: 200-400 nm in diameter). Regular-sized technetium-99m-labeled tin colloid is 400-1000 nm in diameter. In 74 patients, a SLNB was performed using regular-sized tin colloid; small-sized tin colloid was used in 110 patients. Subsequently, all of the patients were immediately followed by ALND. All dissected lymph nodes were evaluated by routine histopathological examination. The clinicopathological characteristics of the two groups were comparable. The lymphoscintigram detected SLN more frequently in the small-sized colloid group than in the regular-sized colloid group (P < 0.01). Small-sized tin colloid was also superior to regular-sized tin colloid in the SLN identification rate (97.3% versus 86.5%; P = 0.01). The mean value for ex vivo counts of the hottest sentinel lymph nodes of the small-sized colloid group was significantly higher than the counts of the regular-sized colloid group (P < 0.01). There was no significant difference in the accuracy between the two groups. It was concluded that SLNB using the small-sized tin colloid was technically feasible and provided higher detection and identification rates than the regular-sized tin colloid.
Adult↗
Intraoperative lymphatic mapping and sentinel lymph node sampling in esophageal and gastric cancer.
Recent studies for SN mapping of esophageal and gastric carcinoma show that the SN concept is valid even for upper GI cancers with multidirectional and complicated lymphatic flow. The relatively high incidence of anatomic skip metastasis can be attributed to aberrant distribution of SNs. An individualized and minimally invasive surgical approach can be applicable to management of esophageal and gastric carcinoma based on SN status. Although there are several issues to be resolved, this novel procedure has the potential for great benefit to improve quality control in the treatment of upper GI cancer. Well-designed clinical trials of lymphatic mapping for upper GI cancer will be essential to determine whether this technique is widely applicable in the management of these tumors.
Esophageal Neoplasms↗
[Molecular alterations in esophageal cancer].
The clinicopathological characteristics of esophageal cancer have gradually been clarified using molecular biologic methods developed over the past 20 years. For example, amplification of the c-erb B gene is a prognostic factor and predictive of lymph node involvement, while the amplification of the cyclin D1 gene is also a prognostic factor and predictive of distant organ metastasis. Alteration of the p16 gene is also a prognostic factor and predicts lymph node involvement. As telomerase activity is almost a unique phenomenon of cancer cells, highly sensitive detection of esophageal cancer cells in the peripheral blood can be performed. Recently, such new methods as comparative genomic hybridization analysis and cDNA microarray analysis have been used to determine meaningful genetic changes. For therapeutic purposes, although tailor-made therapy has been proposed for several years, the validity of these approaches should be confirmed in a well-designed clinical trial. As molecular targeted therapies, tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR) and monoclonal antibodies against EGFR are being studied in clinical trials in Western countries. A clinical trial of p53 gene therapy against esophageal cancer is also promising.
Cyclin D1↗
[Infectious complications after esophageal surgery].
The incidence of wound infection, which is an intrasurgical field infection, is lower than the incidence of pneumonia, which is an extrasurgical field infection, after esophageal cancer surgery. Several trials predicting postoperative infectious complications have been reported. One measured the phytohemagglutinin- and concanavalin A-induced proliferation of peripheral blood mononuclear cells in patients; one measured the white blood cell (WBC) count 2 h after surgery and the decrease in WBC count on first postoperative day; and another showed that the decrease in serum IgG2 level can predict the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) infections. Useful strategies for managing infectious complications have also been reported. Applying mupirocin calcium hydrate ointment to the nasal cavity decreases the incidence of MRSA infections. Autologous blood collection reduces the need for allogeneic transfusion in patients undergoing resection of esophageal cancer, and avoidance of allogeneic transfusion may reduce the risk of postoperative infection. The total exposure to preoperative chemoradiotherapy should be limited to 40 Gy or less to prevent postoperative pneumonia.
Blood Transfusion, Autologous↗
A neo-esophagus reconstructed by cultured human esophageal epithelial cells, smooth muscle cells, fibroblasts, and collagen.
The scientists involved in this study attempted to develop an artificial esophagus constructed of autologous cells grown by cell culture methods on an extracellular matrix. An artificial esophagus consisting of human esophageal epithelial cells, dermal fibroblasts, and smooth muscle cells isolated from the aortic media, was attempted. The purpose of this study was to examine whether smooth muscle cells could be used in the transforming matrix. Human fibroblasts were embedded in Type I collagen superimposed on the collagen layer of smooth muscle cells. Next, human esophageal epithelial cells were cultured on the collagen layer of the fibroblasts. The resulting collagen sheets were cultured in vitro for 1 week, then transplanted on the latissimus dorsi muscles of athymic rats. The sheets were examined histologically at 1 and 2 weeks using hematoxylin eosin and immunologic stain methods (antiactin antibody). At the end of 2 weeks after transplantation, on microscopic observation of the collagen sheets, it appeared that the epithelial layer, the submucosal tissue layer, and the proper muscle layer had been reconstructed. Additionally, the authors successfully isolated smooth muscle cells from the media of the left gastric artery as a surgical specimen by explant cell culture. The ability to transform collagen sheets consisting of esophageal epithelial cells, fibroblasts, and smooth muscle cells from a surgical specimen into a luminal structure may enable clinical application of the artificial esophagus.
Animals↗
A pilot study of combination chemotherapy with S-1 and low-dose cisplatin for highly advanced gastric cancer.
BACKGROUND: The surgical outcome for advanced gastric cancer, even following curative surgery, is associated with a poor prognosis. A pilot study in advanced gastric cancer patients was carried out using pre-operative chemotherapy with S-1 and low-dose cisplatin (CDDP) (TSLD). PATIENTS AND METHODS: Twenty-one patients with stage IV gastric cancer were treated with TSLD as the initial treatment, after informed consent had been obtained. Surgery was performed when curative resection was deemed feasible in selected patients who showed improvement in their tumors. Other regimens including CPT-11 or taxanes were utilized as second-line chemotherapy when the tumor showed no change or progressive disease following TSLD therapy. RESULTS: No patient had a complete response, while 11 had partial responses following TSLD therapy, yielding an overall response rate of 52.4%. Fifteen out of 21 (71.4%) underwent surgery following TSLD therapy, while curative surgery determined by histological investigation was performed in 10 out of 15 (47.6%) patients. No grade 4 toxicities or treatment-related deaths were observed. The following grade 3 toxicities were observed: neutropenia (6 patients), thrombocytopenia (1 patient) and anemia (1 patient). The other toxicities observed, including gastrointestinal toxicity, were grade 2 or less. The median survival time of all patients was 526 days, and 1- and 2-year survival rates were 64.9% and 41.7%, respectively. CONCLUSION: TSLD is a potent regimen with a low toxicity profile for highly advanced gastric cancer.
Adult↗