Is adjuvant chemotherapy necessary in pT1N1 gastric cancer?

BACKGROUND: Due to a lack of consensus on adjuvant treatments for pT1N1 gastric cancer, surgeons face a dilemma when deciding treatments for patients with pT1N1 gastric cancer after gastrectomy. The objective of this study was to determine survival benefits of adjuvant chemotherapy and risk factors for tumor recurrence in gastric cancer patients with pT1N1. METHODS: Between 1996 and 2010, 510 patients who underwent curative resection for pT1N1 gastric cancer at three institutes were divided into two groups: adjuvant chemotherapy group (N = 150) and surgery-only group (N = 360). Disease-free survival rates and risk factors for tumor recurrence were analyzed. RESULTS: During the median follow-up of 78 months, 7.5% of patients experienced tumor recurrence (7.3% in adjuvant chemotherapy group and 7.5% in surgery-only group). The 5-year disease-free survival rate was 91.8% in the adjuvant chemotherapy group and 94.6% in the surgery-only group without significant difference between the two. In univariate analysis, older age (>65 years), male gender, body mass index <25 kg/m2, elevated gross type, and differentiated histology were associated with tumor recurrence. Multivariate analysis showed that advanced age and male gender were independent risk factors for tumor recurrence. In addition, adjuvant chemotherapy showed no benefitial effect on tumor recurrence in pT1N1 gastric cancer. CONCLUSIONS: Adjuvant chemotherapy did not show any oncologically benefitial effect on tumor recurrence, it might be unnecessary for pT1N1 gastric cancer after curative surgery.

Chemoresponse after non-curative gastrectomy for M1 gastric cancer.

BACKGROUND: M1 gastric cancer has a poor oncologic outcome with a median survival of less than 1 year despite aggressive chemotherapy. Recent trials include chemotherapy combined non-curative gastrectomy. This study evaluated the chemoresponse after non-curative gastrectomy in M1 gastric cancer and the survival benefit. METHODS: Between January 2000 and December 2010, 660 patients received chemotherapy for gastric cancer at the Department of Hemato-Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea. Data was collected retrospectively from the medical records. Patients who received preoperative or adjuvant chemotherapy, who underwent other surgeries like gastrojejunal bypass or exploratory laparotomy, who died within 3 months due to seriously advanced gastric cancer, who were lost to follow-up, or whose medical records were unsuitable for data collection were excluded. The remaining 101 patients had received chemotherapy only (CTx group, n = 76) or chemotherapy after non-curative gastrectomy (NCG + CTx group, n = 25). Clinicopathologic characteristics, chemoresponse, and overall survival were compared between the two groups. RESULTS: There were no significant differences between the two groups in clinicopathologic characteristics including age, sex, body mass index (BMI), comorbidity, histologic differentiation, tumor location, clinical T stage, and initial site of distant metastasis. Chemoresponse was checked on two separate occasions from the initiation of chemotherapy: first chemotherapy regimen and until the third regimen change. The NCG + CTx group showed more favorable chemoresponse than the CTx group in both checks (60% and 72% vs. 18.4% and 23.7%). The NCG + CTx group showed longer overall survival than the CTx group (26 vs. 11 months). CONCLUSIONS: Non-curative gastrectomy in M1 gastric cancer could improve chemoresponse and extend overall survival.

Quality of life beyond the early postoperative period after laparoscopy-assisted distal gastrectomy: the level of patient expectation as the essence of quality of life.

BACKGROUND: The aim of this study was to compare the quality of life after the early postoperative period and before reaching 5 years postoperatively between patients who underwent laparoscopy-assisted distal gastrectomy (Group A) and patients who underwent open distal subtotal gastrectomy (Group B). METHODS: The Korean versions of the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and a gastric cancer-specific module, the EORTC QLQ-STO22, were used to assess the quality of life of 80 patients who underwent laparoscopy-assisted distal gastrectomy or open distal subtotal gastrectomy for gastric cancer. The postoperative period ranged between 6 months and 5 years. RESULTS: The global health status/quality of life scores of Groups A and B were 56.0 ± 19.0 and 57.4 ± 18.2, respectively (p = 0.729). Group A experienced worse quality of life in role functioning (p = 0.026), cognitive functioning (p = 0.034), fatigue (p = 0.039), eating restrictions (p = 0.009), and anxiety (p = 0.033). Group A showed a trend to experience worse quality of life in physical functioning, emotional functioning, social functioning, insomnia, and body image, albeit without statistical significance. CONCLUSION: After the early postoperative period and before achieving long-term survival, patients who underwent laparoscopy-assisted distal gastrectomy appeared to experience lower quality of life compared to patients who underwent open distal subtotal gastrectomy. This finding may be associated with the patients' erroneously high expectations of laparoscopy-assisted distal gastrectomy.

Preoperative Standardized Uptake Value of Metastatic Lymph Nodes Measured by 18F-FDG PET/CT Improves the Prediction of Prognosis in Gastric Cancer.

This study assessed whether preoperative maximum standardized uptake value (SUVmax) of metastatic lymph nodes (LNs) measured by F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) could improve the prediction of prognosis in gastric cancer.One hundred fifty-one patients with gastric cancer and pathologically confirmed LN involvement who had undergone preoperative F-FDG PET/CT prior to curative surgical resection were retrospectively enrolled. To obtain nodal SUVmax, a transaxial image representing the highest F-FDG uptake was carefully selected, and a region of interest was manually drawn on the highest F-FDG accumulating LN. Conventional prognostic parameters and PET findings (primary tumor and nodal SUVmax) were analyzed for prediction of recurrence-free survival (RFS) and overall survival (OS). Furthermore, prognostic accuracy of survival models was assessed using c-statistics.Of the 151 patients, 38 (25%) experienced recurrence and 34 (23%) died during follow-up (median follow-up, 48 months; range, 5-74 months). Twenty-seven patients (18%) showed positive F-FDG nodal uptake (range, 2.0-22.6). In these 27 patients, a receiver-operating characteristic curve demonstrated a nodal SUVmax of 2.8 to be the optimal cutoff for predicting RFS and OS. The univariate and multivariate analyses showed that nodal SUVmax (hazard ratio [HR] = 2.71, P < 0.0001), pathologic N (pN) stage (HR = 2.58, P = 0.0058), and pathologic T (pT) stage (HR = 1.77, P = 0.0191) were independent prognostic factors for RFS. Also, nodal SUVmax (HR = 2.80, P < 0.0001) and pN stage (HR = 2.28, P = 0.0222) were independent prognostic factors for OS. A predictive survival model incorporating conventional risk factors (pT/pN stage) gave a c-statistic of 0.833 for RFS and 0.827 for OS, whereas a model combination of nodal SUVmax with pT/pN stage gave a c-statistic of 0.871 for RFS (P = 0.0355) and 0.877 for OS (P = 0.0313).Nodal SUVmax measured by preoperative F-FDG PET/CT is an independent prognostic factor for RFS and OS. Combining nodal SUVmax with pT/pN staging can improve survival prediction precision in patients with gastric cancer.

A new strategy for the diagnosis of MAGE-expressing cancers.

The expression of melanoma antigen gene (MAGE), coding for tumor antigens recognized by cytotoxic T cell, is highly specific to cancer cells, but their use in the detection of a few cancer cells by reverse transcription-polymerase chain reaction (RT-PCR) has been limited by the low frequency of expression of individual MAGE genes. In order to increase MAGE detection rate in RT-PCR assay, here, we designed multiple MAGEs recognizing primers (MMRPs) that can bind to the sequences of cDNA of MAGE-1, -2, -3, -4a, -4b, -5a, -5b and-6 (MAGE 1-6) together. The nested RT-PCR assay using MMRPs, MAGE 1-6 assay, detected MAGE messages of 1 to 5 SNU484 cells in a background of 10(7) SNU638 cells. MAGE detection rate of MAGE 1-6 assay in cancers was higher than that of nested RT-PCR that detects single MAGE gene expression. The expressions of MAGE genes was detected by MAGE 1-6 assay in 70.4% (19/27) of head and neck cancer tissues, 91.7% (11/12) of breast cancer tissues, 75% (9/12) of lung cancer tissues. However, they were not detected in 18 benign lesions and 20 normal head and neck tissues and 30 blood samples from healthy donor. In conclusions, MAGE 1-6 assay can detect any cancer cells that express at least one of eight MAGE subtype genes, and this method may be very useful for the diagnosis of MAGE-expressing cancers.

Mutations of the BAK gene are infrequent in advanced gastric adenocarcinomas in Koreans.

The bcl-2 homologue antagonist/killer (BAK) is a potently apoptosis-inducing gene and plays an important role in modulating apoptosis in epithelial cells. We have analyzed the mutation of the entire coding region of BAK gene in 107 Korean advanced gastric adenocarcinomas by polymerase chain reaction-single strand conformation polymorphism and sequencing. Homozygous deletions were not found in these samples. Only three cases of 107 gastric adenocarcinomas (2.8%) exhibited the BAK mutations. Two of them exhibited missense mutations and the remaining one had a silent mutation. All of these mutations were exclusively detected in exon 2. Mutations in the BAK gene were observed only in advanced gastric adenocarcinomas with extensive metastases of regional lymph nodes. The data presented here suggest that the mutations of BAK gene rarely occurred in advanced gastric adenocarcinomas.

Successful treatment of invasive gastric mucormycosis in a patient with alcoholic liver cirrhosis: A case report.

Gastrointestinal (GI) mucormycosis is a rare and life-threatening invasive fungal infection. GI mucormycosis occur in all parts of the alimentary tract, with the stomach being the most common site. Diabetes mellitus and other types of conditions associated with immunodeficiency, including hematologic malignancies, solid organ transplantation and glucocorticoid therapy, are risk factors for GI mucormycosis. There are few studies reporting cases of gastric mucormycosis in patients with liver cirrhosis, and even fewer reporting the successful treatment of invasive gastric mucormycosis in a patient with liver cirrhosis. This study presents a case of invasive gastric mucormycosis in a patient with liver cirrhosis, which was treated successfully by prompt diagnosis, metabolic support, surgical debridement of involved tissues and antifungal therapy.

Jejunogastric intussusception: a rare complication of gastric cancer surgery.

Jejunogastric intussusception (JGI) is a rare condition and less than 200 cases have been published since its first description in 1914. In addition, JGI is potentially lethal complication of gastrectomy or gastrojejunostomy. We report the case of a 73-year-old man with a history of a Billroth II procedure who presented to the emergency department after 6 hours of epigastric pain and hematemesis. Endoscopy and computed tomography showed intussuscepted jejunum through a gastrojejunostomy that required emergency operation. At laparotomy a retrograde type II, JGI was confirmed and managed by resection of involved intestine. Postoperative recovery was uneventful. This case presents the rare complication of acute jejunogastric intussusception more than 25 years after a Billroth II procedure.

Impact of gender and body mass index on surgical outcomes following gastrectomy: an Asia-Pacific perspective.

BACKGROUND: Although surgeons may expect difficulties in performing gastrectomy on patients with high body mass index (BMI), it is not always the case, especially regarding patient gender. The aim of this study was to evaluate gender as a predictive factor of surgical outcomes related to obesity, as defined by the World Health Organization for the Asia-Pacific region. METHODS: Data of short-term surgical outcomes were obtained from 243 patients following open curative distal subtotal gastrectomy for gastric adenocarcinoma. Patients were classified into two groups by gender, and were further classified by BMI into group A (BMI ≥ 25 kg/m(2)) and group B (BMI < 25 kg/m(2)). The operation time, extent of surgical bleeding, the number of resected lymph nodes, postoperative hospital stay, serum amylase levels, white blood cell count and postoperative complications were accessed for each group. RESULTS: Within male patients, the operation time tended to be longer in group A, albeit without statistical significance (P = 0.075). However, the extent of surgical bleeding was significantly larger in group A (P = 0.002). Within female patients, there were no such differences. When comparisons were made between male and female patients in group A, the operation time was significantly longer in male patients (P = 0.019). The extent of bleeding tended to be larger in males, albeit without statistical significance (P = 0.065). No such differences were seen when comparisons were made between male and female patients in group B. CONCLUSIONS: Disparity in surgical outcomes between male and female patients does exist, particularly in patients with high BMI. Gender adjustment of BMI must be performed when predicting surgical outcomes.

Early gastric cancer with signet ring cell histology remained unresected for 53 months.

The natural course of untreated patients with signet ring cell carcinoma of the stomach remains poorly understood while assumptions have been made to distinguish it from other types of gastric cancer. A 74-year-old Korean woman was diagnosed with early gastric cancer with signet ring cell histology and refused surgery. A satellite lesion was identified 46 months after the initial diagnosis. The patient finally agreed to undergo distal subtotal gastrectomy 53 months following the initial diagnosis. Postoperative histological examination of both lesions confirmed signet ring cell carcinoma associated with submucosal invasion. There was no evidence of lymph node metastasis.

Mitochondrial microsatellite instability in gastric cancer and gastric epithelial dysplasia as a precancerous lesion.

BACKGROUND: Genetic instability in gastric cancer represents a key molecular step that occurs early in the carcinogenesis process. To clarify the role of genetic instability in the progression from gastric dysplasia to gastric cancer, mitochondrial microsatellite instability (mtMSI) was studied in gastric cancer and gastric dysplasia. METHODS: DNA was isolated from paired normal and tumoral tissues in 24 patients with gastric dysplasia (low grade) and 49 patients with gastric cancer. mtMSI was analyzed using eight microsatellite markers. mtMSI in gastric dysplasia was studied prospectively to elucidate the relation between mtMSI and gastric carcinogenesis. RESULTS: mtMSI was found in 5 (10.2%) of 49 gastric cancer patients. The mtMSI phenotype was not associated with age, gender, and Helicobacter pylori infection. However, all of the mtMSI was found in intestinal-type gastric cancer (20.8%, p=0.02). In gastric dysplasia, mtMSI was detected in 3 (12.5%) of 24 patients with gastric dysplasia. mtMSI-positive gastric dysplasia showed a poor prognosis statistically compared to mtMSI negative through progression to high-grade dysplasia or gastric cancer. CONCLUSIONS: These data suggest that mtMSI may be an early and important event in the progression of gastric carcinogenesis, especially in intestinal-type gastric cancer.

Prognostic significance of immunohistochemical expression of p53 and retinoblastoma gene protein (pRB) in curatively resected gastric cancer.

BACKGROUND: The aim of this study was to determine the prognostic significance of the expression of p53 and retinoblastoma (Rb) gene products in cases of curatively resected gastric adenocarcinoma, by immunohistochemical analysis. METHODS: Between January 1996 and December 2001, 736 curatively resected gastric cancer patients underwent immunohistochemical staining for p53 or Rb proteins (pRb), and we retrospectively analyzed the correlation of our results with the clinical outcomes of these cases. RESULTS: High levels of expression of p53 (>25% p53-positive cells) and Rb (>50% Rb-positive cells) proteins were detected in 40.1% and 43.7% of cases, respectively. Tubular type was found to frequently exhibit higher levels of p53 expression (high expression in 44.2%) than signet ring cell type (high expression in 26.0%) (p = 0.042). The incidence of vascular invasion was lower in the high pRb expressors (43.2%) than in the pRb low expressors (56.8%), but this was not a statistically significant discrepancy (p = 0.063). Preoperative CEA levels were found to be low in high pRb expressors: initial CEA level in the high pRb expressors was 2.31 +/- 3.30 ng/mL, and was 5.18 +/- 24.80 ng/mL in the low pRb expressors (p = 0.033). Tumor depth and node metastasis were both independent of the levels of expression of p53 and Rb proteins. The seven-year overall survival rate and relapse-free survival rates of patients were 87.2% and 75.7%, respectively. Multivariate Cox regression analysis indicated that tumor stage, tumor size, patient age and pRb expression were the significant prognostic factors with regard to overall survival, and tumor stage and age were both significant factors with regard to relapse-free survival. CONCLUSION: Immunohistochemical staining of retinoblastoma gene products was an independent prognostic factor for the prediction of overall survival in curatively resected gastric cancer patients.

Prognostic significance of immunohistochemical expression of EGFR and C-erbB-2 oncoprotein in curatively resected gastric cancer.

PURPOSE: The purpose of this study was to investigate the prognostic significance of the expression of EGFR and C-erbB-2 gene products by immunohistochemical analysis for curatively resected gastric adenocarcinoma. MATERIALS AND METHODS: Between January 1996 and December 2001, 739 patients with curatively resected gastric cancer patients underwent immunohistochemical staining for EGFR and C-erbB-2 proteins, and we retrospectively analyzed their correlation with the clinical outcome. RESULTS: The over expressions of EGFR and C-erbB-2 were 25.4% and 26.2%, respectively. The over expressions of EGFR was associated with the more poorly differentiated tumor (p=0.000) and with neuronal invasion (p=0.03). Over expression of C-erbB-2 was associated with less vascular invasion (p=0.001). Tumor depth or node metastasis was not related to the over expression of EGFR or C-erbB-2. The seven-year overall survival and relapse-free survival rates were 87.2% and 75.8%, respectively. Upon multivariate Cox regression analysis, the tumor stage, tumor size and patient age were important prognostic factors for overall survival, and tumor stage was the important factor for relapse-free survival. Over expressions of EGFR or c-erbB-2 were not significant prognostic factors. CONCLUSION: Immunohistochemical staining of EGFR and C-erbB-2 gene products were not independent prognostic factors for predicting the overall survival and the relapse-free survival in curatively resected gastric cancer.