Gene expression profiles as predictors of poor outcomes in stage II colorectal cancer: A systematic review and meta-analysis.

PURPOSE: The use of adjuvant therapy in stage II colorectal cancer (CRC) remains controversial. There is a need to identify more effective predictors than the traditional staging system to aid therapeutic decision-making. We performed a systematic review and meta-analysis of gene expression profiles (GEPs) to assess their utility for risk stratification and prediction of poor outcomes in stage II CRC. PATIENTS AND METHODS: We performed a comprehensive literature search through December 2007. Studies were included if they reported GEP-based assays in patients with stage II CRC, and either subsequent cancer recurrence or death within 3 years. The prognostic likelihood ratio (LR) and odds ratio (OR) were calculated with 95% confidence intervals and pooled using the fixed-effects method. The weighted average sensitivity, specificity, and accuracy were also reported. RESULTS: Eight cohorts involving 271 patients contributed to the analysis. The average accuracy, sensitivity, and specificity were 81.9%, 76.2%, and 84.5%, respectively, with a prognostic LR of 4.7 (95% CI, 3.2-6.8) and a prognostic OR of 15.1 (95% CI, 7.9-28.6). No evidence for significant interstudy heterogeneity was noted in either analysis. Subgroup analysis found no difference in results for the prediction of cancer recurrence or death. CONCLUSION: This analysis demonstrates the promising potential of using GEP assays as predictors of poor outcomes in stage II CRC, such as cancer recurrence or death. To maximize their utility and availability, further studies will be needed to identify and validate specific gene signatures for poor prognosis in stage II CRC.

Current status of adjuvant therapy for colon cancer.

Due to its frequency and persistently high mortality, colorectal cancer represents a major public health problem. The use of adjuvant chemotherapy has improved prognosis in stage III disease, but much work remains to be done in optimizing adjuvant treatment, including refinement of ability to predict disease course and response to chemotherapy. The FOLFOX4 regimen is now considered standard treatment for stage III disease. Combinations of irinotecan and 5-fluorouracil (5-FU) have not proven to be more effective than 5-FU/folinic acid (FA). Oral fluoropyrimidines (eg, capecitabine, UFT + FA) now offer an alternative to intravenous 5-FU. Adjuvant chemotherapy for stage II colorectal cancer is more controversial. Use of adjuvant chemotherapy does not appear to be justified in patients with no particular risk factors (T3N0 with no poor prognosis factor). In contrast, the risk:benefit ratio in patients with one or more poor prognostic factors (T4 tumor, occlusion or perforation, poorly differentiated tumor, vascular invasion, or < 10 lymph nodes examined) appears to favor adjuvant treatment with FOLFOX4. Ongoing adjuvant trials are evaluating bevacizumab and cetuximab combined with 5-FU and oxaliplatin, and are examining the utility of such potential predictive markers as tumor microsatellite instability and loss of heterozygosity. Duration of therapy and prevention of oxaliplatin neurotoxicity are other critical areas for future research.

[Gene expression profiling in colon cancer]. / Génomique somatique et pronostic des cancers colorectaux.

Identification of new prognostic factors for colon cancer with no lymph node involvement may improve the selection of patients for adjuvant chemotherapy. The aim of this study was to assess the possibility of using gene expression profiling for this purpose. Fifty patients operated on for stage II colon cancer were included. Twenty-five of these patients relapsed, while the other 25 remained disease-free for at least 5 years. MRNA was extracted from fresh-frozen biopsies and hybridized to the Affymetrix GeneChip HGU133A. One thousand six hundred random splits of the 50 patients into a training set and a validation set were considered. For each split, a prognostic combination was derived from the training set (selection of the 30 genes most differentially expressed between patients who recurred and those who did not, by linear discriminant analysis), and its prognostic performance was assessed with the validation set. On average, accuracy was 76%, sensitivity 85%, and specificity 68%. A total of 6,124 genes were included in at least one of the 1,600 predictive combinations, and 55 genes were included in more than 100 combinations. This study supports the possibility of predicting the prognosis of non-metastatic colon cancer by tumor gene expression profiling. It also shows the highly variable gene composition of predictive combinations.

Ischemic colitis.

BACKGROUND: Ischemic colitis almost always occurs in older patients. Because life expectancy is increasing, more and more often physicians will face this problem. The aim of this study was to identify factors leading to surgery in the acute phase of the disease, and to evaluate mortality and long-term follow-up evaluation. METHODS: We performed a retrospective study of 73 patients (mean age, 73 y) in the Department of General and Digestive Surgery. Diagnosis was obtained by endoscopic and pathologic procedures. The median follow-up period was 4.5 years (range, 2-9 y). RESULTS: Thirty-six patients had 1 or more co-existing medical diseases. All the patients had either lower intestinal bleeding (45 patients) or diarrhea (28 patients). Thirty-three patients had undergone surgery (45%). In the surgical group, 13 patients underwent immediate surgery for abdominal tenderness and/or shock. Eight of these patients died (62%). Out of 60 patients undergoing nonsurgical immediate management, 1 patient died (septic shock). Delayed surgery was indicated in 20 out of the 59 remaining patients for clinical or endoscopic aggravation. Six of these patients died (30%). Multivariate analysis selected 4 factors of severity: age younger than 80 years, male sex, absence of bleeding, and abdominal tenderness. In the follow-up period 13 patients died from a cardiovascular disease. The 2- and 5-year actuarial survival rates of patients who survived the initial hospitalization were 88% and 68%, respectively. CONCLUSIONS: Multivariate analysis selected the risk factors of severity. In severely ill patients serial endoscopic evaluations are the best indicator for surgery before appearance of tenderness, septic shock, full-thickness gangrene, and perforation. At discharge, anticoagulant or anti-arrhythmic therapy should be considered for patients who have cardiovascular disease.

Stage II colon cancer prognosis prediction by tumor gene expression profiling.

PURPOSE: This study mainly aimed to identify and assess the performance of a microarray-based prognosis predictor (PP) for stage II colon cancer. A previously suggested 23-gene prognosis signature (PS) was also evaluated. PATIENTS AND METHODS: Tumor mRNA samples from 50 patients were profiled using oligonucleotide microarrays. PPs were built and assessed by random divisions of patients into training and validation sets (TSs and VSs, respectively). For each TS/VS split, a 30-gene PP, identified on the TS by selecting the 30 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Two schemes were considered: single-split validation, based on a single random split of patients into two groups of equal size (group 1 and group 2), and Monte Carlo cross validation (MCCV), whereby patients were repeatedly and randomly divided into TS and VS of various sizes. RESULTS: The 30-gene PP, identified from group 1 patients, yielded an 80% prognosis prediction accuracy on group 2 patients. MCCV yielded the following average prognosis prediction performance measures: 76.3% accuracy, 85.1% sensitivity, and 67.5% specificity. Improvements in prognosis prediction were observed with increasing TS size. The 30-gene PS were found to be highly-variable across TS/VS splits. Assessed on the same random splits of patients, the previously suggested 23-gene PS yielded a 67.7% mean prognosis prediction accuracy. CONCLUSION: Microarray gene expression profiling is able to predict the prognosis of stage II colon cancer patients. The present study also illustrates the usefulness of resampling techniques for honest performance assessment of microarray-based PPs.

Diffuse large and small bowel necrosis in catastrophic antiphospholipid syndrome.

The catastrophic variant is an accelerated form of the antiphospholipid syndrome resulting in multiorgan failure because of multiple small vessel occlusions. We report a case of catastrophic antiphospholipid syndrome in a patient with subacute cutaneous lupus erythematosus and ischemic bowel, who presented with acute abdominal pain due to diffuse right colon and small bowel necrosis requiring large resection, associated with acute respiratory distress syndrome, thrombocytopenia and disseminated intravascular coagulation. Histopathological examination of resected tissues showed diffuse arteriolar and venous thrombosis but no vasculitis, and mesenteric artery lumen severely narrowed by intimal fibrosis. The patient died 15 days after admission despite treatment with anticoagulation, steroids, continuous hemofiltration and plasma exchange. Ischemic bowel and diffuse intestinal necrosis may be secondary to the antiphospholipid syndrome, and a high level of suspicion and an early diagnosis are required.

[Positron emission tomography of gastrointestinal carcinomas]. / Résultats de la tomographie par emission de positons dans les cancers de l'appareil digestif.

We evaluated positon emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in 120 patients with intestinal malignancies, focusing on its diagnostic yield and influence on the surgical strategy. PET had a sensitivity of 67% and a specificity of 100% for metastases in 28 patients with cardio-esophageal carcinoma. PET detected 64% of 22 primary pancreatic carcinomas, and had a sensitivity of 70% and a specificity of 83% for metastases. In two cases, PET showed false-positive signs of peritoneal metastasis (not found at laparotomy). Among 70 patients with recurrent or metastatic colorectal carcinoma, eight had signs of local recurrence of rectal carcinoma treated by abdominoperineal resection; PET gave four true-positive, one false-negative, and three false-positive results. PET was better than computed tomography (CT) for the diagnosis of peritoneal metastasis, but its sensitivity was only 58%. The diagnostic value of PET for hepatic metastases (87%) was similar to that of CT (77%) and sonography (87%). The diagnostic sensitivity of PET for pulmonary metastases (82%) was similar to that of CT (84%). PET modified the surgical strategy in two (7%) of 28 patients with cardio-esophageal carcinoma, one (5%) of 22 patients with pancreatic carcinoma, and 22 (33%) of 70 patients with colorectal carcinoma (appropriately in 11 cases, inappropriately in 11 cases). These disappointing results suggest that PET must be thoroughly evaluated in this setting before being widely adopted.

Exploration of global gene expression in human liver steatosis by high-density oligonucleotide microarray.

Understanding the molecular mechanisms underlying fatty liver disease (FLD) in humans is of major importance. We used high-density oligonucleotide microarrays (22.3 K) to assess the mechanisms responsible for the development of human liver steatosis. We compared global gene expression in normal (n=9) and steatotic (n=9) livers without histological signs of inflammation or fibrosis. A total of 34 additional human samples including normal (n=11), steatosis (n=11), HCV-related steatosis (n=4) or steatohepatitis associated with alcohol consumption (n=4) or obesity (n=4) were used for immunohistochemistry or quantitative real-time PCR studies. With unsupervised classification (no gene selection), all steatotic liver samples clustered together. Using step-down maxT multiple testing procedure for controlling the Family-Wise Error-Rate at level 5%, 110 cDNAs (100 over- and 10 underexpressed) were found to be differentially expressed in steatotic and normal livers. Of them were genes involved in mitochondrial phosphorylative and oxidative metabolism. The mean ratio of mitochondrial DNA to nuclear DNA content was higher in liver steatosis compared to normal liver biopsies (1.12+/-0.14 vs 0.67+/-0.10; P=0.01). An increased expression of genes involved in inflammation (IL-1R family, TGFB) was also observed and confirmed by quantitative RT-PCR or immunochemistry. In steatohepatitis, an increase of the protein expression of mitochondrial antigens, IL-1R1, IGF2 and TGFB1 was also observed, interleukin 1 receptor being always strongly expressed in steatohepatitis linked to alcohol or obesity. In conclusion, mitochondrial alterations play a major role in the development of steatosis per se. Activation of inflammatory pathways is present at a very early stage of steatosis, even if no morphological sign of inflammation is observed.

Ischemic preconditioning modulates the expression of several genes, leading to the overproduction of IL-1Ra, iNOS, and Bcl-2 in a human model of liver ischemia-reperfusion.

Ischemia triggers an inflammatory response that precipitates cell death during reperfusion. Several studies have shown that tissues are protected by ischemic preconditioning (IP) consisting of 10 min of ischemia followed by 10 min of reperfusion just before ischemia. The molecular basis of this protective effect is poorly understood. We used cDNA arrays (20K) to compare global gene expression in liver biopsies from living human liver donors who underwent IP (n=7) or not (n=7) just before liver devascularization. Microarray data were analyzed using pairedt test with a type I error rate fixed at alpha = 2.5 10(6) (Bonferroni correction). We found that 60 genes were differentially expressed (36 over- and 24 underexpressed in preconditioning group). After IP, the most significantly overexpressed gene was IL-1Ra. This was confirmed by immunoblotting. Differentially expressed were genes involved in apoptosis (NOD2, ephrin-A1, and calpain) and in the carbohydrate metabolism. A significant increase in the amount of the anti-apoptotic protein Bcl-2 in preconditioned livers but no change in the cleavage of procaspase-3, -8, and -9 was observed. We also observed an increase in the amount in the inducible nitric oxide synthase. Therefore, the benefits of IP may be associated with the overproduction of IL-1Ra, Bcl-2, and NO countering the proinflammatory and proapoptotic effects generated during ischemia-reperfusion.

Gene expression profiling of nonneoplastic mucosa may predict clinical outcome of colon cancer patients.

PURPOSE: This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in Stage II and III colon cancer patients. METHODS: Tumor and nonneoplastic mucosa mRNA samples from 12 colon cancer patients were profiled using the Affymetrix HGU133A GeneChip. Six of 12 patients experienced a metachronous metastasis, whereas the 6 others remained disease-free for more than five years. Three datasets were constituted, including, respectively, the gene expression measures in tumor samples (T), in adjacent nonneoplastic mucosa samples (A), and the log-ratio of the gene expression measures (L). The step-down procedure of Westfall and Young and the k-nearest neighbor class prediction method were applied on T, A, and L. Leave-one-out cross-validation was used to estimate the generalization error of predictors based on different numbers of genes and neighbors. RESULTS: The most frequent results were one false prediction with the A-based predictors (95 percent) and two false predictions with the T- and L: -based predictors (65 and 60 percent, respectively). A-based predictors were more stable (i.e., less sensitive to changes of parameters, such as numbers of genes and neighbors) than T- and L: -based predictors. Informative genes in A-based predictors included genes involved in the oxidative and phosphorylative mitochondrial metabolism and genes involved in cell-signaling pathways and their receptors. CONCLUSIONS: This study suggests that one can build a prognosis predictor for Stage II and III colon cancer patients, based on microarray gene expression measures, and suggests the potential usefulness of nonneoplastic mucosa for this purpose.

Colon cancer prognosis prediction by gene expression profiling.

This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in stage II and III colon cancer patients. Tumour (T) and non-neoplastic mucosa (NM) mRNA samples from 18 patients (nine with a recurrence, nine with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. The k-nearest neighbour method was used for prognosis prediction using T and NM gene expression measures. Six-fold cross-validation was applied to select the number of neighbours and the number of informative genes to include in the predictors. Based on this information, one T-based and one NM-based predictor were proposed and their accuracies were estimated by double cross-validation. In six-fold cross-validation, the lowest numbers of informative genes giving the lowest numbers of false predictions (two out of 18) were 30 and 70 with the T and NM gene expression measures, respectively. A 30-gene T-based predictor and a 70-gene NM-based predictor were then built, with estimated accuracies of 78 and 83%, respectively. This study suggests that one can build an accurate prognosis predictor for stage II and III colon cancer patients, based on gene expression measures, and one can use either tumour or non-neoplastic mucosa for this purpose.

Clinicopathologic, phenotypic, and genotypic characteristics of gastrointestinal mesenchymal tumors.

BACKGROUND & AIMS: Variability in the frequency of KIT mutations in gastrointestinal mesenchymal tumors has been reported in the literature, and their prognostic value remains uncertain. This retrospective multicenter study included 276 patients with gastrointestinal mesenchymal tumors. METHODS: We detected c-kit and CD34 protein expression by immunohistochemistry. Mutations in exons 11 and 9 of KIT and exons 12 and 18 of PDGFR were detected by length analysis of polymerase chain reaction products and direct DNA sequencing. RESULTS: Eighty-seven percent of the tumors analyzed were c-kit positive, with gastric tumors expressing CD34 more frequently than other tumors (86% vs. 52%; P < 0.001). KIT exon 11 mutations were detected in 90 of 179 (50.3%) of c-kit-positive and 12% of c-kit-negative tumors. These mutations showed variation in their length and location. Mutations were heterozygous in 94% of cases. Mutations were more frequent in CD34( +) tumors than in CD34( -) tumors ( P < 0.01), and 9% of tumors had a second mutation in exon 11. Mutations in exon 9 of KIT were present in 5.1% of the gastrointestinal stromal tumors, and mutations of the PDGFR were present in 11% of the KIT -nonmutated tumors. Patient's age, the primary location, size, necrosis, and mitotic counts of tumors were associated with metastases in c-kit-positive tumors. However, mitotic activity was the only independent factor identified in multivariate analysis ( P < 0.001). KIT mutations were slightly more frequent in metastatic than in nonmetastatic tumors (61% vs. 46%; P = 0.06). Deletions of codons 562-579 were more strongly associated with metastases than were deletions of codons 550-561 ( P = 0.0001). CONCLUSIONS: Mutations in KIT or PDGFR were detected in 58.4% of the c-kit-positive and also in some c-kit-negative tumors.

Prospective evaluation of blood concentration of mitochondrial DNA as a marker of toxicity in 157 consecutively recruited untreated or HAART-treated HIV-positive patients.

Highly active antiretroviral therapy (HAART) can cause mitochondrial toxicity. The concentration of mitochondrial DNA (mtDNA) in peripheral blood cells has been reported to be a marker of this toxicity. However, these observations are controversial and were drawn from small series. Thus, we analysed the value of blood mtDNA as a marker of mitochondrial toxicity in a large cohort of human immunodeficiency virus (HIV)-infected out-patients during routine clinical evaluations. Real-time quantitative PCR was used to determine the mtDNA to nuclear DNA (nDNA) ratio in peripheral blood mononuclear cells from 157 consecutive HIV-1-infected patients (13 naive, 144 receiving HAART) and 30 HIV-1-uninfected patients. The mtDNA to nDNA ratio was significantly lower in both groups of HIV-infected patients than in the control group. No significant difference was observed between treated and naive HIV-infected patients. Lactataemia was significantly lower in controls than in the group of HIV-treated patients. None of the treated patients had lactataemia >5 mmol/l or bicarbonates <20 mmol/l. Triglyceride levels were significantly higher in the HAART-treated patients than in the nontreated patients. Clinical symptoms of lipodystrophy were observed in 62 HAART-treated patients. These symptoms were not associated with an abnormal mtDNA to nDNA ratio or plasma triglyceride concentration. The mtDNA to nDNA ratio was lower in DDI/D4T-treated patients than in AZT/3TC-treated patients. In conclusion, there are no obvious links between the mtDNA to nDNA ratio in peripheral mononuclear cells and any clinical symptoms or lactate level. Thus, the mtDNA to nDNA ratio in leukocytes does not seem to be an accurate marker of mild and/or long-term mitochondrial toxicity.

Cardio-esophageal cancer. Is 18Fluorodeoxyglucose positron emission tomography worthwhile?

BACKGROUND/AIMS: 18Fluorodeoxyglucose positron emission tomography has been proposed for the preoperative staging of carcinomas of the esophagus and gastric cardia. The aim of this study was to assess its diagnostic value and its influence on therapeutical decisions. METHODOLOGY: Twenty-eight patients with a cancer of the esophagus or gastric cardia underwent a 18Fluorodeoxyglucose positron emission tomography on a gamma camera with coincidence detection electronics, in addition to our standard preoperative procedures (barium swallow, liver ultrasonography, chest X-ray). Four types of lesions were searched for: primary tumor, abdominal and mediastinal lymph nodes, and distant metastases. Results of 18Fluorodeoxyglucose positron emission tomography were compared to pathological findings. RESULTS: Sensitivity for the primary tumor was 86%. Sensitivity for mediastinal and abdominal lymph nodes was 75 and 54%, respectively, whereas specificity was 100%. Distant metastases were detected in 4 patients: liver metastasis in 2 patients and bone metastasis in 2 patients. Results of 18Fluorodeoxyglucose positron emission tomography influenced therapeutical decisions for 2 patients. CONCLUSIONS: 18Fluorodeoxyglucose positron emission tomography seems to be worthwhile in the preoperative staging of carcinomas of the esophagus and gastric cardia, mainly because it may detect distant metastases.

The MTHFR 677C > T polymorphism is associated with an increased risk of hepatocellular carcinoma in patients with alcoholic cirrhosis.

Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, plays a major role in the provision of methyl groups for DNA methylation and in the production of dTMP for DNA synthesis. Different polymorphisms have been described for this enzyme, the most studied being the C677T, which has been shown to be associated with predisposition to colorectal cancer in patients who consume a high alcohol diet. The aim of this study was to determine whether the MTHFR polymorphism is related to hepatocellular carcinoma (HCC) in patients with alcoholic cirrhosis. MTHFR genotypes were determined in 300 liver transplant patients, 72 of whom had alcoholic cirrhosis with HCC and 122 of whom had alcoholic cirrhosis without HCC. The remaining patients were transplanted for HCC on normal liver (n = 27) or viral cirrhosis with HCC (n = 49) or without HCC (n = 30). We also tested 80 healthy subjects. Among the group of patients transplanted for alcoholic cirrhosis, the frequency of MTHFR variants CC versus CT and TT was significantly higher in patients with HCC than in patients without macroscopic evidence of HCC (P = 0.02). This difference was not observed between patients with and without HCC developed either on viral cirrhosis or on non-cirrhotic liver. If we considered all the patients transplanted for HCC, the MTHFR CC genotype was significantly higher in patients who had developed HCC on alcoholic cirrhosis rather than on viral cirrhosis (P = 0.002) or on non-cirrhotic livers (P = 0.02). The relative risk for HCC in subjects with alcoholic cirrhosis and the CC genotype was 2.03. These results suggest that the MTHFR CC genotype increases the risk to develop HCC in patients who consume a high alcohol diet.

Rectal cancer surgery in patients more than 80 years of age.

BACKGROUND: This retrospective study aimed to compare the prognosis for rectal cancer in patients more than 80 years old with that observed in younger patients. METHODS: Patients operated on for a rectal adenocarcinoma, from 1980 to 1998, were divided into two groups: group 1 (>80 years, n = 92); group 2 (<80 years, n = 276). RESULTS: There were significant differences between the two groups with regard to the sex ratio, the American Society of Anesthesiologists (ASA) classification, the emergency presentation, and the curative operation rate. The operative mortality rate was 8% in group 1, 4% in group 2 (P = 0.26). The overall 5-year survival rate was 35% in group 1, 53% in group 2 (P = 0.0004). In patients operated on for cure, the cancer-specific 5-year survival rate was 50% in group 1, 59% in group 2 (P = 0.08). CONCLUSIONS: The prognosis for rectal cancer in patients over 80 years is not significantly different from that of younger patients. Surgery should not be restricted on the basis of age.

[18 F-fluorodeoxyglucose positron emission tomography for characterization and initial staging of pancreatic tumors]. / Tomographie par émission de positons au (18 F)fluorodésoxyglucose dans l'évaluation initiale des tumeurs du pancréas.

AIM: To evaluate positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) for characterizing and initial staging of pancreatic tumors and to determine its impact on therapeutic strategy. PATIENTS AND METHODS: This study included 24 patients with pancreatic tumor who underwent PET before treatment. Twenty-two patients had a malignant tumor and two had a benign tumor. The PET scan was performed after intravenous injection of FDG with a gamma camera. PET findings were compared with histology of the pancreatic tumor (n=24), liver metastases (n=5), peritoneal metastases (n=5), and lymph node metastases (n=5). Absence of metastasis or lymph node involvement was determined by surgery or by CT scan, ultrasonography, magnetic resonance imaging and at least two months follow-up. RESULTS: The sensitivity of the PET scans to identify pancreatic carcinoma was 64% (95% confidence interval 44-84%). PET scans could not be interpreted for lymph node involvement adjacent to the tumor. For liver metastases, the PET scan was positive in 3 out of 5 patients. For peritoneal metastases, the PET scan was positive in 4 out of 5 patients but was doubtful in one. There were two false positives. Among the 4 cystic tumors, the PET scan was positive for 2 malignant tumors and negative for 2 benign tumors. Surgical strategy was modified in only one of the 24 patients on the basis of PET findings. CONCLUSION: The sensitivity of PET for the diagnosis of primary malignant pancreatic tumor was found to be low. The contribution of FDG-PET to the surgical decision appears to be limited to the detection of metastases or lymph node involvement distant from the tumor, contraindicating surgery. Nevertheless, the sensitivity of FDG-PET is lower than that of laparoscopy for peritoneal metastases. Indications for PET should be included in an evaluation of therapeutic decision making and cost analysis.

Early gastric carcinoma: spread and multicentricity.

BACKGROUND: In early gastric carcinoma (EGC), after subtotal gastrectomy, recurrent lesions limited to the gastric remnant are the cause of about 20% of deaths from recurrence. Therefore, it has been suggested to perform total gastrectomy in all cases of EGC. METHODS: We studied a case series of 82 consecutive patients operated on for an EGC, with a mean follow-up time of 72 months (range, 1-120 months). Subtotal distal gastrectomy was performed 61 patients, total gastrectomy in 15, and other procedures in 6. Outcome measures were recurrence and causes of mortality, focusing on patients with resection line involvement and multifocal lesions. RESULTS: EGC was limited to the mucosa in 43 patients and had invaded the submucosa in 39. Ten patients had a lymph node involvement. In 4 patients having had a subtotal gastrectomy, resection line involvement was detected. In 3 patients, the involvement was detected peroperatively on frozen sections, and a re-resection was performed. In the fourth patient, the involvement was detected postoperatively, but follow-up endoscopies failed to show any residual tumor. In 17 patients, multifocal lesions were observed. No recurrence was observed in the gastric remnant of patients having undergone a subtotal gastrectomy. CONCLUSION: In distal EGC, a subtotal gastrectomy may be performed under two conditions: (1) careful endoscopic and peroperative examination of the upper part of the stomach to detect multifocal lesions and (2) a systematic frozen-section assessment of the resection margin to avoid inadequate resection.