Progression of remnant gastric cancer is associated with duration of follow-up following distal gastrectomy.

AIM: To re-evaluate the recent clinicopathological features of remnant gastric cancer (RGC) and to develop desirable surveillance programs. METHODS: Between 1997 and 2008, 1149 patients underwent gastrectomy for gastric cancer at the Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Japan. Of these, 33 patients underwent gastrectomy with lymphadenectomy for RGC. Regarding the initial gastric disease, there were 19 patients with benign disease and 14 patients with gastric cancer. The hospital records of these patients were reviewed retrospectively. RESULTS: Concerning the initial gastric disease, the RGC group following gastric cancer had a shorter interval [P < 0.05; gastric cancer vs benign disease: 12 (2-22) vs 30 (4-51) years] and were more frequently reconstructed by Billroth-I procedure than those following benign lesions (P < 0.001). Regarding reconstruction, RGC following Billroth-II reconstruction showed a longer interval between surgical procedures [P < 0.001; Billroth-II vs Billroth-I: 32 (5-51) vs 12 (2-36) years] and tumors were more frequently associated with benign disease (P < 0.001) than those following Billroth-I reconstruction. In tumor location of RGC, after Billroth-I reconstruction, RGC occurred more frequently near the suture line and remnant gastric wall. After Billroth-II reconstruction, RGC occurred more frequently at the anastomotic site. The duration of follow-up was significantly associated with the stage of RGC (P < 0.05). Patients diagnosed with early stage RGC such as stage I-II tended to have been followed up almost every second year. CONCLUSION: Meticulous follow-up examination and early detection of RGC might lead to a better prognosis. Based on the initial gastric disease and the procedure of reconstruction, an appropriate follow-up interval and programs might enable early detection of RGC.

Differences of the lymphatic distribution and surgical outcomes between remnant gastric cancers and primary proximal gastric cancers.

BACKGROUND: Although remnant gastric cancer (RGC) following distal gastrectomy is located in the proximal stomach, little is known about the differences of the lymphatic distribution and surgical outcomes between RGC and primary proximal gastric cancer (PGC). METHODS: Between 1997 and 2008, 1,149 patients underwent gastrectomy for gastric cancer. Of these, 33 (2.9%) RGC patients and 207 (18.5%) PGC patients were treated at our department. We reviewed their hospital records retrospectively. RESULTS: Compared with the PGC patients, those with RGC had a slightly higher age at onset (p=0.09), higher incidence of undifferentiated cancer (p=0.06), higher incidence of vascular invasion (p=0.09), and higher incidence of T4 (p=0.07). Gastrectomy for RGC involved greater blood loss (p<0.005), longer surgical duration (p=0.01), combined resection, and high incidence of complications. However, the survival rate for RGC patients was similar to that for PGC patients (p=0.67). 2) Patients with RGC had a different pattern of lymph node metastasis compared with that in PGC. Particularly in advanced RGC with pT2-T4 tumors, RGC frequently demonstrated jejunal mesentery lymph node metastases (RGC vs. PGC, 35% vs. 0%) and splenic hilar lymph node metastases (RGC vs. PGC, 17% vs. 10%). The jejunal mesentery lymph node metastases were detected only following Billroth II reconstruction (Billroth I vs. Billroth II, 0% vs. 67%). CONCLUSION: Although the clinical behaviors of the two gastric cancers were different, the survival rates were similar. The pattern of metastasis indicates that the jejunal mesentery and splenic hilar lymph nodes should be specifically targeted for en bloc resection during complete gastrectomy in RGC.

Quantification of circulating plasma DNA fragments as tumor markers in patients with esophageal cancer.

UNLABELLED: The quantity and quality of circulating DNA fragments was analyzed by quantitative real-time polymerase chain reactions (qPCR) in plasma from patients with esophageal carcinomas, in order to assess their diagnostic value. PATIENTS AND METHODS: Plasma was collected preoperatively from 24 patients with esophageal cancer and 21 healthy controls. qPCR was performed using two primer sets for the beta-actin gene, amplifying short and long segments. RESULTS: The DNA concentrations in both the short and long assays of esophageal cancer patients were significantly higher than the controls (p<0.001). The area under the receiver-operating characteristic curve was 0.83 (short) and 0.91 (long) for esophageal cancer patients versus the controls. There was also a significant difference in DNA integrity (short/long) between esophageal cancer patients and the control group (p= 0.001). CONCLUSION: qPCR assays for plasma DNA concentrations and their integrity can serve as new diagnostic markers for screening and monitoring patients with esophageal cancer.

Quantification of plasma cell-free DNA in patients with gastric cancer.

BACKGROUND: The circulating DNA concentration and integrity was examined by a quantitative polymerase chain reaction (qPCR) in the plasma from patients with gastric cancer and their diagnostic value for the detection of gastric cancer assessed. PATIENTS AND METHODS: Plasma samples were collected preoperatively from 53 patients with gastric cancer and 21 healthy controls. qPCR was performed using two different primer sets for the beta-actin gene, amplifying short and long segments. DNA integrity was calculated as the ratio of concentrations in both assays. RESULTS: The DNA concentrations in the short and long assays of the gastric cancer patients were significantly higher (p=0.03 and p<0.0001, respectively) than those of the control group. The DNA integrity was also higher in cancer patients than that of the controls, however the difference was not significant (p=0.07). CONCLUSION: The plasma DNA concentration assay may serve as a new diagnostic marker for the screening and monitoring of patients with gastric cancer.

Circulating cell-free mRNA in plasma as a tumor marker for patients with primary and recurrent gastric cancer.

BACKGROUND: The diagnostic value of circulating mRNA for the early detection of primary and recurrent gastric cancer was evaluated. PATIENTS AND METHODS: Circulating hTERT and MUC1 mRNA were amplified in the plasma from 52 gastric cancer patients (40 preoperative and 12 postoperative patients) and 20 healthy controls. The results were compared with those of a circulating cancer cell assay and methylation-specific polymerase chain reaction assay. RESULTS: Cell-free mRNA of the analyzed genes was detected in 6 (15%) preoperative gastric cancer patients (hTERT: 3 and MUC1: 4 patients) and 2 follow-up patients. These mRNAs were not detected in the plasma from healthy volunteers. There was no correlation between the results of the cell-free mRNA and the other assays. CONCLUSION: Detection of circulating cell-free mRNA might serve as a new complementary tumor marker for gastric cancer.

Circulating tumor cells and aberrant methylation as tumor markers in patients with esophageal cancer.

BACKGROUND: This study was designed to compare the detection rates of conventional tumor markers with two molecular diagnostic approaches on blood samples from patients with esophageal squamous cell cancer. MATERIALS AND METHODS: Preoperative blood samples were obtained from 44 esophageal cancer patients and were subjected to CEA-specific reverse transcriptase-polymerase chain reaction (RT-PCR) assay and methylation-specific polymerase chain reaction (MSP) assay for p16, E-cadherin and RARbeta genes. RESULTS: Circulating tumor cells were detected in 12 patients (27%); 14 patients (32%) had aberrant methylation in the promoter region of at least one gene (6, 4 and 4 patients, for p16, E-cadherin and RARbeta, respectively). No abnormality was detected by either assay in control plasmas. Altogether, 23 patients (53%) had a positive result in either molecular assay. There was no correlation between either assay result and those of conventional serum markers. CONCLUSION: The RT-PCR and MSP assays can serve as complementary markers for screening and monitoring esophageal cancer patients.

[Quantification of circulating plasma DNA fragments as tumor markers in patients with esophageal and gastric cancer].

The quantity and quality of circulating DNA fragments was analyzed by quantitative real-time polymerase chain reactions (qPCR) in plasma from patients with esophageal and gastric cancer, in order to assess their diagnostic value. Plasma was collected preoperatively from 24 patients with esophageal cancer 53 patients with gastric cancer and from 21 healthy controls. qPCR was performed using two primer sets for the BETA-actin gene, amplifying short (102 bp) and long (253 bp) segments. The DNA concentrations in both the short and long segment assays of both cancer patients were significantly higher than the controls. The difference of concentrations between disease group and controls was more significant in esophageal cancer patients. The area under the receiver-operating characteristic curve was 0.83 (short) and 0.91 (long) for esophageal cancer patients, and 0.75 (short) and 0.67 (long) for gastric cancer versus the controls. There was also a significant difference in DNA integrity (short/long) between esophageal cancer patients and the control group (p = 0.001). qPCR assays for plasma DNA concentrations and their integrity can serve as new diagnostic markers for screening and monitoring patients with esophageal and gastric cancer.

Correlation between serum DNA methylation and prognosis in gastric cancer patients.

BACKGROUND: Gastric carcinogenesis is thought to involve multiple genetic and epigenetic changes. The relationships between the promoter methylation status of relevant genes in the serum and outcomes in patients undergoing curative gastrectomy for cancer were investigated. MATERIALS AND METHODS: Pre-operative serum samples obtained from 97 gastric cancer patients, who underwent radical gastrectomy, were subjected to methylation-specific polymerase chain reaction (MSP) assays for the p16, E-cadherin and retinoic acid receptor beta (RARbeta) genes. RESULTS: Promoter hypermethylation of p16, E-cadherin and the RARbeta gene was detected in sera from 18 (19%), 24 (25%) and 24 patients (25%), respectively. Altogether, 47 patients (48%) showed hypermethylation of at least one gene analyzed. Survival curves differed significantly between groups defined by the methylation status of E-cadherin (p<0.05), but not those defined by p16 or RARbeta (p =0. 77 and 0. 19, respectively). CONCLUSION: Serum MSP assays can provide not only diagnostic, but also prognostic information in gastric cancer.

[Plasma methylation-specific polymerase chain reaction as a diagnostic tool for esophageal cancer patients].

This study was designed to perform methylation-specific polymerase chain reaction (MS-PCR) assay for p16, E-cadherin, and retinoic acid receptor beta genes on peripheral blood samples from patients with esophageal squamous cell cancers, and compare the results of MS PCR with conventional serum tumor markers and the CEA-specific reverse transcriptase polymerase chain reaction (RT-PCR) assay. Preoperative blood samples were obtained from 30 patients with esophageal cancer, and were subjected to MS PCR and RT-PCR assays. Eleven patients (37%) showed aberrant methylation of the promoter region of at least one gene. On the other hand, circulating tumor cells were detected in 11 patients (37%). There was no correlation between both results and conventional tumor markers. The MS-PCR and RT-PCR assays can serve as complementary diagnostic markers for screening and monitoring patients with esophageal cancers.

[An early detection of recurrence using reverse transcriptase-polymerase chain reaction (RT-PCR) and methylation-specific polymerase chain reaction (MSP) from peripheral blood in patients after gastrectomy].

Several molecular approaches, using peripheral blood of patients with cancers, have been assessed recently for ability to detect various primary and recurrent cancers at an early stage. One is the reverse transcriptase polymerase chain reaction (RT-PCR) analysis, which can detect a small number of circulating cancer cells. Another is the methylation-specific polymerase chain reaction (MSP), which detects tumor-specific alterations of cell-free serum DNA released from tumor into the circulation by necrosis and/or apoptosis. In the present study, we set out to assess the diagnostic value of the RT-PCR assay and the MSP assay for an early detection of recurrent diseases in patients after curative gastrectomy. Two of the 25 patients (8%) exhibited a CEA specific signal in their peripheral blood. On the other hand, seven patients (28%) showed aberrant methylation of the promoter region of at least one gene (3 patients for p16, 3 for E-cadherin, 3 for RARbeta genes, and 1 for CDH4 respectively). No abnormal signal was detected in sera from volunteers who served as controls. Of 10 patients who developed recurrences, a CEA-specific signal and aberrant methylation was demonstrated in plasma samples of 1 and 4 patients, respectively. One patient, without definite findings of recurrence at the time of analysis, developed recurrences 6 months later. Both assays can serve as markers that allow selection of those cases requiring more intensive screening and aggressive postoperative treatment.

Comparison of serum aberrant methylation and conventional tumor markers in gastric cancer patients.

BACKGROUND/AIMS: This study was designed to compare a methylation-specific polymerase chain reaction (MSP) assay for three genes [p16, E-cadherin, and retinoic acid receptor beta (RARbeta)] and conventional serum tumor markers using blood samples from gastric cancer patients. METHODOLOGY: Preoperative blood samples obtained from 63 consecutive patients with gastric cancer were subjected to MSP and conventional serum marker assays. RESULTS: MSP assay detected hypermethylation of p16 in 17 patients (27%), E-cadherin in 15 patients (24%), and RARbeta in 11 patients (17%). Altogether, 32 patients (51%) showed hypermethylation in serum samples. By contrast, only 21 (33%) patients exhibited elevations of serum carcinoembryonic antigen or carbohydrate antigen 19-9. There was no correlation between MSP results and conventional tumor markers. CONCLUSIONS: The detection rate for MSP was higher than that of conventional tumor markers in serum of gastric cancer patients. Both assays can serve as complementary markers that allow for selection of cases requiring more intensive screening or aggressive postoperative treatment.

Detection of aberrant methylation as a tumor marker in serum of patients with gastric cancer.

BACKGROUND: This study aimed to detect hypermethylation in serum DNA from patients with gastric cancer at various stages and to assess the assay for early detection of primary and recurrent disease. MATERIALS AND METHODS: Preoperative serum samples were obtained from 109 patients with gastric cancer. Blood samples were subjected to methylation-specific polymerase chain reaction analysis to determine the methylation status of the promoter region of the p16 and E-cadherin genes. RESULTS: Forty patients (37%) showed hypermethylation of the promoter region in one or both genes (p16, 20 patients; E-cadherin, 26 patients). Of 36 patients with early-stage gastric cancers, 10 (28%) showed aberrant methylated signals. No aberrant methylation was detected in the serum DNA from 10 healthy volunteers. CONCLUSION: Aberrant promoter hypermethylation may prove useful as a new serum marker for gastric cancer.