The advantage of the PTD classification is that if the PTD classification were to be used as a guide for gastric resection procedures, preservation of the pylorus would become possible without diminishing the prognosis in patients with cT1N0 cancer located in zone T.
Abstract. Indocyanine green (ICG) fluorescence imaging represents a promising method for sentinel node (SN) biopsy in laparoscopic gastric surgery due to its signal stability. In the present study, the suitability and optimal settings of ICG fluorescence imaging for SN biopsy in early gastric cancer were determined. Patients with single primary superficial-type adenocarcinoma of the stomach, lesions <5 cm in diameter, and no evident nodal metastasis and out of indication for endoscopic submucosal dissection were enrolled. The day prior to surgery, ICG solution was endoscopically injected into four quadrants of the submucosal layer of the tumor. The Photodynamic Eye was used to detect ICG fluorescence. Bright nodes were defined as clearly fluorescent nodes. A total of 72 patients were enrolled; 11 cases presented with metastasis, and of these, 10 could be diagnosed by bright node biopsy. The adequate concentration and injection volume of ICG was determined to be 50 µg/ml (x100) and 0.5 mlx4 points, respectively. There was 1 false-negative case, and this was attributed to the failure of the frozen section diagnosis. These results suggested that ICG fluorescence imaging for SN biopsy in laparoscopic surgery for early gastric cancer is feasible. However, a weakness of ICG fluorescence imaging is the subjectivity of bright node evaluation.
This study evaluated the feasibility and pharmacology of intraperitoneal docetaxel (IP docetaxel) when administered weekly for 3 consecutive weeks, followed by 1 week without treatment. A total of 24 patients with peritoneal carcinomatosis of gastric cancer (10 preoperative, 7 postoperative and 7 recurrent) were enrolled in this study. Docetaxel was dissolved in an isotonic saline to a final 1 liter solution and was administered in a 1 h dosage of 25, 35, 45 and 60 mg/m 2 to determine the maximum tolerated dose (MTD). To measure the docetaxel concentration, blood and peritoneal fluid samples were collected 0.5, 1, 2, 3, 6 and 24 h after administering the drug to 15 patients. A total of 109 chemotherapy cycles were administered, with a median of four cycles per patient (range 2-9). The MTD of the weekly IP docetaxel was defined at 60 mg/m 2. At a docetaxel dosage of 60 mg/m 2 per week, the dose-limiting events of grade 3 abdominal pain and grade 3 diarrhea, which may be associated with local toxicity, occurred. Peak concentrations of peritoneal fluid ranged from 24.5 to 68.7 μg/ml. The mean ratio of the area under concentration (AUC) in the peritoneal fluid to the plasma concentration was 515. Furthermore, the mean of plasma AUC by IP docetaxel was 5.63 μg•h/ml versus that of IV docetaxel at a dose of 60 mg/m 2. The response rate of the preoperative IP docetaxel was 80% (4 CR, 4 PR, 1 NC and 1 PD), which was judged with laparoscopy and peritoneal lavage cytology. Gastrectomy, with D2 lymph node dissection, was performed on all of the patients evaluated as CR. The weekly IP docetaxel demonstrated a low toxicity and high efficacy for peritoneal carcinomatosis with dual anti-cancer effects via the peritoneal surface and capillary blood supply due to its unique pharmacokinetic property.
Abstract. Tissue inhibitor of metalloproteinase-3 (TIMP-3) has an inhibitory effect on tumor development, growth and metastasis due to its interaction with matrix metalloproteinases (MMPs). We investigated the prognostic significance of TIMP-3 gene promoter methylation in esophageal squamous cell carcinoma (ESCC). TIMP-3 methylation was analyzed by MethyLight, a quantitative and methylation-specific PCR method. Hypermethylation was found in 9/51 (18%) surgically resected ESCC samples and was associated with reduced disease-free (p=0.0039) and overall survival (p=0.0047). Upon multivariate analysis, it was found to be an independent prognostic parameter for poor survival and was associated with earlier recurrence after surgery (p=0.0238), especially via pleural dissemination (p=0.001). Expression levels for TIMP-3 protein and for several MMPs were analyzed by Western blot analysis in 20 pairs of ESCC and adjacent normal tissue. The expression of MMP-2, -7 and -9 proteins in tumor tissue was significantly higher than in corresponding normal mucosa (p=0.0051, 0.0064 and 0.0004, respectively). In contrast, the expression of TIMP-3 protein in tumor tissue was significantly lower than in matched normal mucosa (p=0.0152). Tumors with TIMP-3 hypermethylation expressed lower levels of TIMP-3 protein compared to those without hypermethylation (p=0.0357). These results demonstrate that TIMP-3 hypermethylation is associated with lower TIMP-3 protein expression in ESCC and with poor patient survival due to a high frequency of recurrence by pleural dissemination. IntroductionEsophageal carcinoma is one of the most common types of cancer and is associated with unfavorable patient survival due to the high proportion of patients that present with advanced stage disease. Recent progress in surgical procedure has allowed radical lymph node dissection in esophageal cancer (1). However, postoperative local and distant recurrence is still a major problem in the management of this cancer (2,3). Although our general understanding of the mechanisms of cancer development and progression have improved, the molecular and biological data relating to esophageal cancer are still quite limited and poorly understood. The identification of good prognostic markers in esophageal cancer remains of major importance for improving the clinical management and outcome of patients with this disease.Matrix metalloproteinases (MMPs) are a group of Ca 2+ -dependent, zinc-containing enzymes that degrade proteins in the extracellular matrix (4). More than 25 MMPs have been described to date and are classified on the basis of amino acid homology, peptide structure and in vitro substrate specificity. MMPs are implicated in all aspects of tumor progression; they enhance tumor-induced angiogenesis, destroy local tissue architecture to allow tumor growth, and break down basement membranes during the process of metastatic spread. The expression of MMP-1, -2, -3, -7, -9, -11 and -13 and membrane-type MMPs (MT-MMPs) and their prognostic significance in esophageal squ...
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