Biomarker analysis in stage III-IV (M0) gastric cancer patients who received curative surgery followed by adjuvant 5-fluorouracil and cisplatin chemotherapy: epidermal growth factor receptor (EGFR) associated with favourable survival.

The aim of this study was to analyse the impact of epidermal growth factor receptor (EGFR), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), aurora kinase (ARK) A/B, and excision repair cross-complementing gene 1 (ERCC1) on the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin (FP) after curative gastric resection. Normal and cancer tissue were separately obtained from gastrectomy samples of 153 patients with AJCC stage III-IV (M0) who subsequently treated with adjuvant FP chemotherapy. TS, DPD, TP, ERCC1, and ARK proteins were measured by immunohistochemistry (IHC). EGFR expression was investigated using a standardized IHC with the EGFR PharmDx assay. Amplification of EGFR gene was analysed using fluorescent in situ hybridisation (FISH). In multivariate analysis, stage, ratio of positive to removed lymph nodes, and EGFR expression were significant prognostic factors for overall survival. Patients with higher EGFR expression had better overall survival than those with lower expression (relative risk: 0.475 (95% confidence interval, 0.282-0.791, P=0.005). Low EGFR expression might be a predictive marker for relapse in curative resected stage III-IV (M0) gastric cancer patients who received adjuvant FP chemotherapy.

Sentinel node biopsy for cT1 and cT2a gastric cancer.

AIMS: To evaluate the feasibility and accuracy of sentinel node (SN) biopsy for gastric cancer. PATIENTS AND METHODS: One hundred patients with gastric cancer diagnosed as cT1 (n=80) or cT2a (n=20) were enrolled. Indocyanine green-stained SNs were analysed by hematoxylin and eosin staining (n=100) and by cytokeratin immunohistochemistry (n=50). RESULTS: SNs were identified in 94 of the 100 patients and the mean number of SNs was 4.4 (range, 1-12). Of these 94 patients, 14 patients had lymph node metastases. Two patients with T1 and one patient with T2 had metastases in non-SNs alone by hematoxylin and eosin staining (diagnostic accuracy =97.3% in T1 and 95.0% in T2). All three patients with a false negative result had a tumour, which was more than 4 cm in size and signet ring cell histology. In two of them, the tumour was located at lesser curvature. By immunohistochemical staining, three patients with T1 and one patient with T2 were found to have lymph node micrometastases in non-SNs alone among 45 patients (diagnostic accuracy =92.1% in T1, 85.7% in T2). CONCLUSION: SN biopsy using indocyanine green can be performed rapidly and easily with a high detection rate and accuracy in patients with T1 gastric cancer. However, it should be performed with caution for large tumours with a signet ring cell histology located at lesser curvature due to the possibility of a false negative result.

Intraoperative gastroscopy for gastric surgery.

BACKGROUND: Few reports are available on the use of intraoperative gastroscopy for gastric surgery. METHODS: The details of 33 patients (25 early gastric cancers and eight gastric submucosal tumors) who underwent intraoperative gastroscopy from June 2003 to June 2004 were analyzed. The type of operation or resection margin was determined by evaluating both sides of the stomach simultaneously by combined operative and gastroscopic methods. RESULTS: Preoperative endoscopic clipping was done preferentially for early gastric cancer. However, when precise localization was needed, intraoperative gastroscopy was used. Curative gastric resection was possible in 25 early gastric cancer patients after accurate lesion localization. Laparoscopic wedge resections of submucosal tumors were performed in seven patients without stenosis by combined laparoscopic and gastroscopic methods. CONCLUSIONS: Intraoperative gastroscopy can be used effectively during gastric surgery for early gastric cancer or submucosal tumors and can be regarded as a modern stethoscope to gastric surgeons.

Predictors of operative morbidity and mortality in gastric cancer surgery.

BACKGROUND: The aim of this study was to identify factors that predict morbidity and mortality in gastric cancer surgery. METHODS: Data on 719 consecutive patients who underwent operations for gastric cancer at Seoul National University Hospital between January and December 2002 were reviewed. RESULTS: Overall morbidity and mortality rates were 17.4 per cent (125 patients) and 0.6 per cent (four patients) respectively, and the rates of surgical and non-surgical complications were 14.7 per cent (106 patients) and 3.3 per cent (24 patients). Morbidity rates were higher in patients aged over 50 years (odds ratio (OR) 1.04 (95 per cent confidence interval (c.i.) 1.02 to 1.06)), when the gastric tumour was resected with another organ (36 per cent for combined resection versus 15.4 per cent for gastrectomy only; OR 3.25 (95 per cent c.i. 1.76 to 6.03)) and when gastrojejunostomy was used for reconstruction after subtotal gastrectomy (17.0 per cent for Billroth II versus 9.5 per cent for Billroth I; OR 2.00 (95 per cent c.i. 1.05 to 3.79)). Only three patients (2.8 per cent) with a surgical complication underwent reoperation, two for adhesive obstruction and one for intra-abdominal bleeding. CONCLUSION: Age, combined resection and Billroth II reconstruction after radical subtotal gastrectomy were independently associated with the development of complications after gastric cancer surgery.

Prognostic significance of the expression of Smad4 and Smad7 in human gastric carcinomas.

BACKGROUND: Transforming growth factor-beta (TGF-beta) modulates the growth and function of many cells, including those with malignant transformation. Smad proteins have been identified as major components in the intracellular signaling of TGF-beta family members. PATIENTS AND METHODS: To clarify the correlations between clinicopathologic profiles and the patient's survival, the expression of common mediator Smad (Smad4) and inhibitory Smad (Smad7) were evaluated immunohistochemically in 304 consecutive gastric carcinomas using the tissue array method. RESULTS: Positive Smad4 expression was observed in 266 (87.5%) tumors and positive Smad7 expression in 98 (32.2%) tumors. The prognosis of patients with a Smad4-positive tumor was significantly better than that of the patients with a negative tumor. The survival rate was significantly higher in patients with negative Smad7 expression than those with positive Smad7 expression. In subgroup analysis according to TNM (tumour-node-metastasis) stage, both Smad4 and Smad7 showed most significant prognostic differences in stage I gastric cancer patients. Multivariate analysis indicated that tumor size, depth of invasion, lymph node metastasis and Smad7 expression were independent prognostic factors. CONCLUSION: Enhanced expression of the TGF-beta signaling inhibitor Smad7 may present one of the novel mechanisms of TGF-beta resistance in human gastric carcinomas.

A phase III randomized trial of 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil and mitomycin C versus 5-fluorouracil alone in curatively resected gastric cancer.

BACKGROUND: A phase III single-center randomized trial was performed in order to determine whether the addition of mitomycin C (MMC) and/or doxorubicin to 5-fluorouracil (5-FU) as adjuvant chemotherapy could influence survival in patients with curatively resected gastric cancer. PATIENTS AND METHODS: A total of 416 patients who had undergone curative resection for stage IB-IIIB gastric adenocarcinoma were stratified according to the stage and type of surgery, and then randomized to receive one of the three chemotherapy regimens, 5-FU alone (F) or 5-FU and MMC (FM) or 5-FU, doxorubicin and MMC (FAM) within 5 weeks after surgery. RESULTS: Of 416 patients registered, 395 (133 in F, 131 in FM and 131 in FAM) were assessable. Median follow-up duration was 91 months. Five-year overall survival rates were 67.2% for F, 67.0% for FM and 66.7% for FAM (P = 0.97). Five-year disease-free survival rates were 62.1% for F, 63.3% for FM and 62.5% for FAM (P = 0.83). Hematological toxicities were more frequent in the FM and FAM groups, whereas stomatitis was more common in the F group. CONCLUSIONS: Compared with adjuvant 5-FU alone, the addition of MMC and/or doxorubicin to 5-FU did not influence survival in patients with resected gastric cancer.

The timing and characterization of p53 mutations in progression from atypical ductal hyperplasia to invasive lesions in the breast cancer.

The main reason for the recent interest in p53 is that almost 50% of human cancers contain p53 gene mutations. The majority of studies on p53 alterations in breast cancer have been limited to the isolated cases of ductal carcinoma in situ and infiltrating ductal carcinoma. The aims of this study were to determine the status and timing of p53 mutation in the progression from atypical ductal hyperplasia to invasive cancer, and to evaluate the patterns of p53 mutations in noninvasive and invasive lesions. Available lesions of invasive (n=88) and noninvasive (n=76) lesions were microdissected in 107 paraffin-embedded tissues (19 ductal carcinomas in situ, 57 invasive carcinomas with intraductal components, and 31 pure invasive carcinomas) and double-strand DNA sequencing was performed in exon 4-9 of the p53 gene. Among in situ cancers without invasive disease 36.8% had p53 mutations whereas in situ cancer with concurrent invasive disease showed p53 mutations in 33.3% of cases. In particular, two of seven atypical ductal hyperplasias harbored p53 alterations (one insertion and one missense mutation) in exon 8. The invasive component harbored p53 mutations in 30 of 88 cases (34.1%). We also discovered a novel deletion of 14 bp in exon 6 of two invasive lesions. The invasive component (1.33+/-0.13) carried a greater number of p53 mutations than its counterparts (1.19+/-0.10) and demonstrated more frequent multiple mutations (23.3% vs. 15.4%), but without statistical significance. Moreover, no statistical significance could be attached to the mutation frequency in the zinc-binding domains (26.7% vs. 15.4%), the directly DNA contact region (13.3% vs. 15.4%) and the missense mutation of p53 (50.0% vs. 57.7%) of the two groups. Based on our results, in spite of the small number of the lesions investigated, p53 mutation can occur at the stage of atypical ductal hyperplasia. The hypermutability and the specific p53 mutations involving the biologically functional domain (e.g., zinc binding domain or DNA contact region) have an insignificant influence on invasive progression in the breast cancer.

Influence of the number of lymph nodes examined on staging of gastric cancer.

BACKGROUND: Nodal staging for gastric cancer according to the 1997 Union Internacional Contra la Cancrum tumour node metastasis classification is based on the number of metastatic lymph nodes. The aim of this study was to evaluate whether the number of lymph nodes examined affected staging of gastric cancer. METHODS: A retrospective study was performed in 4789 consecutive patients with gastric cancer, who had undergone curative resection (R0) from 1986 to 1995. Patients were classified according to the number of nodes examined. The number of metastatic lymph nodes and stage-stratified survival were compared. RESULTS: There were significant differences in the number of metastatic lymph nodes and survival in stage IIIA between patients with 15 or more lymph nodes and those with fewer than 15 nodes. In analysis restricted to patients with 15 or more nodes, stage-stratified survival did not vary significantly with lymph node yields for any stage except IIIB, in which there was a significant difference between the subgroup with fewer than 20 examined lymph nodes and patients with 35 or more nodes. CONCLUSION: The number of lymph nodes examined did not significantly affect node staging of gastric cancer as long as at least 15 nodes were examined. For stage IIIB, more than 15 lymph nodes may be required for optimal staging.

Fluorodeoxyglucose positron emission tomography for detection of recurrent or metastatic breast cancer.

Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a noninvasive imaging technique capable of identifying primary tumors and metastases with high sensitivity and accuracy. The aim of this study was to evaluate the diagnostic accuracy of whole-body FDG-PET imaging for the detection of recurrent or metastatic breast cancer after surgery. Whole-body FDG-PET imaging was performed on 27 patients with suspected recurrent breast carcinoma. PET images were evaluated qualitatively for each patient and lesion. FDG-PET scans showed that there were 61 reference sites of malignant or benign lesions in 27 patients. In a patient-based analysis, FDG-PET scans correctly identified 16 of 17 patients with recurrent or metastatic disease and 8 of 10 without recurrence, resulting in a sensitivity, specificity, and accuracy of 94%, 80%, and 89%, respectively. In a lesion-based analysis, FDG-PET scans correctly identified 46 of 48 lesion sites with recurrent or metastatic disease and 11 of 13 without recurrence. The overall sensitivity, specificity, and accuracy for all lesion sites were 96%, 85%, and 93%, respectively. FDG-PET scans revealed unsuspected recurrent or metastatic diseases in 8 of 27 (30%) of patients and 11 of 20 (55%) distant metastatic lesions. In 13 patients treatment was altered by the outcome of the PET scan. We concluded that whole-body FDG-PET scan is a useful diagnostic imaging modality for detecting recurrent or metastatic breast carcinoma in patients suspected of having recurrent disease after primary surgery.

Cyclin E overexpression as an independent risk factor of visceral relapse in breast cancer.

AIM: Prognostic value of the cyclin E overexpression in breast cancer has not been clearly established, especially in relation to the pattern of recurrence. We investigated the implication of cyclin E overexpression for the pattern of recurrence in Korean breast cancer patients. METHODS: Using immunohistochemical methods, we retrospectively examined the cyclin E expression level in breast cancer specimens from 128 women who underwent curative breast surgery, and correlated the levels of expression with the pattern of relapse in patients. RESULTS: Cox model-based multivariate analysis indicated that distant relapse could be predicted by the number of positive axillary lymph nodes, high cyclin E expression, and the younger age (<35 years) of the patient. We tested further the association of cyclin E overexpression with the specific types of recurrence; multivariate analyses indicated that adjusted relative risks of bone and visceral relapse as the first events among high cyclin E group were 2.46 (95% confidence interval (CI), 0.86-7.02) (P=0.092), and 3.98 (95% CI, 1.23-12.94) (P=0.022), respectively. On the other hand, cyclin E overexpression was not associated with the risk of locoregional relapse. CONCLUSION: Our data suggest that cyclin E overexpression in primary breast carcinoma tissue could independently predict the risk of distant relapse, especially of visceral relapse, as the first failure after curative breast surgery.

Relationship between the Val158Met polymorphism of catechol O-methyl transferase and breast cancer.

A case-control study was performed to assess the potential influence of catechol O-methyl transferase (COMT) genotype on the risk of breast cancer in Korean women. One hundred and sixty-three histologically confirmed incident breast cancer cases and 163 age- and menopausal status-matched control individuals with no present or previous history of cancer were selected as study subjects. COMT genetic polymorphism was determined by gel electrophoresis after NlaIII enzyme digestion of amplified DNA. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression after adjustment for known or suspected risk factors of breast cancer. Women with at least one COMT lower enzyme activity associated allele (COMT-L) were at elevated risk for breast cancer (OR = 1.7, 95% CI = 1.04-2.78) compared with those homozygous for high enzyme activity associated COMT-H alleles. Among women with low (> or = 23.1) body mass index the COMT-L allele containing genotypes posed a marginally significant increased risk of breast cancer compared to the COMT-HH genotype (OR = 1.8, 95% CI = 0.95-3.48). Women with at least one COMT-L allele who had experienced a full-term pregnancy when aged over 30 years or were nulliparous had 2.7-fold increased risk; however, this increase did not reach statistical significance (OR = 2.7, 95% CI = 0.64-11.35). Furthermore, never-drinking and never-smoking women with at least one COMT-L allele were at increased risk of breast cancer compared to those with COMT-HH genotype with ORs of 2.0 (95% CI = 1.23-3.38) and 1.7 (95% CI = 1.04-2.62), respectively. These results are consistent with studies showing that COMT genotype of lower enzyme activity might be related to increase in risk of breast cancer, and extend this finding to Korean women.

Methylation in the p53 promoter is a supplementary route to breast carcinogenesis: correlation between CpG methylation in the p53 promoter and the mutation of the p53 gene in the progression from ductal carcinoma in situ to invasive ductal carcinoma.

Aberrant methylation in the CpG sites located in the promoter region of several tumor suppressor genes has been reported in various types of cancers. However, the methylation status of the p53 promoter has not been clearly determined and no information is available on its role in breast cancer. The aim of the study was to determine the presence and timing of the methylation of CpG sites in the p53 promoter, in the progression from ductal carcinoma in situ to invasive cancer. We also explored the correlation between the CpG methylation of the p53 promoter and p53 mutation during the progression of breast cancer. The corresponding lesions of both the invasive and noninvasive types were microdissected in paraffin-embedded tissue of 26 breast carcinomas. Bisulfite-modified DNA sequencing for methylation status in the p53 promoter was carried out, and double-strand DNA sequencing was performed in the promoter region and exons 4 to 9 of the p53 gene. CpG site methylation in the p53 promoter was detected in three cases (11.5%). Two noninvasive and three invasive lesions harbored CpG methylation in the p53 promoter. Methylations in more than one site were observed in three lesions, all of which contained methylation in two sites. The methylated CpG sites were located near the AP1 and YY-1 binding sites and at the YY-1 binding site. The p53 mutation was not found in the lesions where methylation in p53 promoter region was evident. In 16 cases (61.5%), neither methylation nor p53 mutation was detected. We conclude that the methylation in the p53 promoter region is found in the breast cancer irrespective of the status of invasion, and that the hypermethylation in the p53 promoter region is an alternative pathway to tumorigenesis where there is no p53 gene mutation.

A Clinicopathological Analysis of Recurrent Gastric Cancer.

PURPOSE: This study was designed to investigate the correlation between the clinicopathologic characteristics and the recurrence pattern of gastric cancer and to define survival difference according to treatment modality after diagnosis of recurrence. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 4184 patients who had undergone radical surgery for primary gastric cancer from 1986 through 1996. Clinicopathologic factors were analyzed for the relationship of each factor with the pattern of recurrence. And the survival after diagnosis of recurrence was compared among the treatment modalities. RESULTS: Recurrence pattern was confirmed in 1141 patients. Loco-regional recurrence occurred in 291 patients (20.1%), peritoneal recurrence in 383 (26.5%), distant recurrence in 290 (20.1%), and mixed recurrence in 177 (12.3%), respectively. Early recurrence (less than 2 years) occurred in 767 (69.3%), intermediate recurrence (2~5 years) in 286 (25.8%), and late recurrence (more than 5 years) in 54 (4.9%). In multivariate analysis, T stage, N stage, size of tumor and perineural invasion were independent prognostic factors for recurrence. Median survival from diagnosis of recurrence was 24.2 months in the curative operation group, 7.7 months in the chemotherapy group, 7.1 months in the non-curative operation group and 3.3 months in the conservative treatment group, respectively (p=0.000). CONCLUSION: The clinicopathological analysis of recurrent gastric cancer showed recurrent patterns and prognostic factors. Curative resection is suggested to have survival benefit in recurrent gastric cancer patients, although it was possible in patients with limited extent of disease.

Flow cytometric analysis of primary tumors and their corresponding metastatic nodes in breast cancer.

Human breast carcinoma is biologically heterogeneous, and its clinical course may vary from one which is indolent to one which rapidly progresses. Although it is the metastasis rather than the primary tumor that ultimately overwhelms the patients, studies concerning the DNA pattern have focused on the primary tumors. This study was undertaken to identify heterogeneities between primary tumors and metastases, and to evaluate the prognostic significance of the ploidy pattern and the S-phase fraction (SPF) of metastatic nodes in axillary node positive patients. Seventy-four frozen specimens of the primary and corresponding metastatic nodes from 37 patients have been analyzed by flow cytometry and the SPF calculated. The results of ploidy pattern analysis in primaries revealed 25 diploidy (67.6%) and 12 aneuploidy (32.4%), while those in metastasis showed 17 diploidy (46.0%) and 20 aneuploidy (54.0%). The aneuploidy group in metastatic nodes had the poorer histological grade (85.0% vs. 15.0%, p = 0.02), and more mean metastatic nodes (5.75 +/- 2.10 vs. 3.05 +/- 1.56, p = 0.018), and more frequent lymphatic vessel invasion (65.0% vs. 11.8%, p = 0.031) than its counterpart. Decreased expression of ER (70.6% vs. 25.0% p = 0.006) and increased expression of c-erbB2 (65.0% vs. 23.5%, p = 0.012) were observed in the aneuploidy of metastatic nodes. The group with higher SPF in metastatic nodes had more metastatic nodes (5.47 +/- 2.31 vs. 4.00 +/- 1.78, p = 0.042), and the higher incidence of lymphatic vessel invasion (57.9% vs. 22.2%, p = 0.027), and poor histological grade (71.4% vs. 37.5%, p = 0.039). In conclusion, the cell populations in metastatic nodes revealed DNA pattern which differed from that of primary tumors. The ploidy pattern and SPF in metastatic nodes might be considered as discriminate measure for risk factors in breast cancer patients with positive axillary node.

Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk.

To evaluate the potential association between GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a South Korean study population consisting of 189 histologically confirmed incident breast cancer cases and their 189 age-matched control subjects with no present or previous history of cancer. A multiplex polymerase chain reaction method was used for the genotyping analyses and statistical evaluations were performed by unconditional logistic regression model. The GSTM1 null genotype was significantly associated with breast cancer risk in premenopausal women [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1-3.7], but not in the postmenopausal women (OR = 0.9, 95% CI = 0.5-1.9), nor in all women grouped together (OR = 1.3, 95% CI = 0.8-1.1). The GSTT1 null genotype posed a similar risk of breast cancer with an OR of 1.6 (95% CI = 1.0-2.5) for the total breast cancer group, OR of 1.7 (95% CI = 0.9-3.2) for pre-menopausal women, and OR of 1.3 (95% CI = 0.6-2.8) for post-menopausal women. The breast cancer risk associated with concurrent lack of both GSTM1 and GSTT1 genes was 2.2 (95% CI = 1.1-4.5), and the risk increased as the number of null genotype increased (P for trend = 0.03). When the data were stratified by the known risk factors of breast cancer, a significant interaction was observed between the GSTM1 genotypes and alcohol consumption (P for interaction = 0.03). An especially remarkable risk of breast cancer was observed for alcohol-consuming premenopausal women lacking both the GSTM1 and GSTT1 genes (OR = 5.3, 95% CI = 1.0-27.8) compared to those with both of the genes. Our findings thus suggest a novel gene-environment interaction which plays an important role in the individual susceptibility to breast cancer. p6

Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.

BACKGROUND: This randomized controlled trial was to determine whether a combination chemotherapy regimen that contains anthracycline (doxorubicin and cyclophosphamide [AC]) is superior to the conventional cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] combination in premenopausal women with axillary lymph node positive Stage II breast carcinoma. METHODS: Premenopausal women with lymph node positive breast carcinoma were stratified according to age (younger than 35 or 35 years or older) and the number of positive axillary lymph nodes (1-3, 4-9, or >/= 10) and then randomly assigned to receive either doxorubicin 40 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenously (i.v.) every 3 weeks or cyclophosphamide 100 mg/m(2) orally on Days 1 through 14, methotrexate 40 mg/m(2) and 5-fluorouracil 500 mg/m(2) i.v. on Days 1 and 8 every 4 weeks. Both arms were scheduled for six cycles. RESULTS: The median follow-up was 57 months. Eighteen of the 55 AC patients developed recurrence compared with 16 of the 69 CMF patients. The corresponding 5-year recurrence free survival rates were 64% and 78%, respectively (P = 0.12). The site of the first recurrence for AC patients was locoregional in 7%, distant in 22%, and combined in 4%. The corresponding data for the CMF arm were 4%, 16%, and 3%, respectively. Six AC patients died compared with 9 CMF patients. The corresponding 5-year survival rates were 90% and 86%, respectively (P = 0.96). More leukopenia (52%, mostly Grade 1-2) occurred in the CMF arm than in the AC arm (33%, P = 0.001), but no febrile episode was accompanied with leukopenia. CONCLUSIONS: This study showed no difference between AC and CMF with respect to both disease free and overall survival rates in premenopausal women with axillary lymph node positive breast carcinoma.

Effect of protease inhibitor on ischemia-reperfusion injury to rat liver.

Liver failure due to ischemia-reperfusion injury, believed to be closely related to the generation of oxygen-free radicals, is a serious problem during liver surgery. Gabexate mesilate, a synthetic protease inhibitor, suppresses the extracellular release of oxygen-free radicals in the microvascular endothelium. To determine its effects on ischemia-reperfusion injury to the liver, we performed experiments with rats. We divided the animals into two ischemia-reperfusion groups: an experimental group, which underwent ischemic injury for 30 minutes, along with the infusion of gabexate mesilate, and a control group, which underwent injury only. Each group was then divided into four subgroups: ischemic injury only and 60-, 120-, and 180-minute reperfusion injury. The test parameters were tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) in serum and superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) in liver and lung tissues. The experimental group had a significantly higher liver SOD and catalase levels and a significantly lower level of liver and lung MDA than the control groups. TNFalpha levels in the experimental groups were significantly lower during the early phase, but a comparison of IL-6 levels between the two groups yielded no differences. Levels of lung catalase and SOD were not significantly different between the two groups. We concluded that protease inhibitor suppressed liver ischemia-reperfusion injury, and that it was due to an increase of antioxidant or suppression of oxygen-free radicals. The roles of TNFalpha and IL-6 in liver reperfusion injury were not clear, though TNFalpha might have had an effect during the early phase. With liver ischemia-reperfusion injury, the mechanism of lung involvement might be different from that of liver involvement.

Detection of cancer in augmented breasts by positron emission tomography.

OBJECTIVE: To assess the diagnostic efficiency of positron emission tomography with 18-fluorine fluorodeoxyglucose in detecting breast cancer in augmented breasts. DESIGN: Retrospective study. SETTING: University hospital, Korea. SUBJECT: 9 cases or 8 patients with breasts augmented with paraffin or silicone. INTERVENTION: FDG-PET, mammography, and ultrasonography RESULTS: The mammogram detected the breast cancer in only 1 of 3 patients, and ultrasonography gave a false positive result in 1 patient with an augmented breast. In contrast, PET predicted all the cancers and 5/6 benign lesions. 2/3 breast cancers had axillary FDG uptake interpreted as showing metastatic involvement, and in 1 case with cancer with no axillary lymph node involvement there was no FDG uptake in the axilla, which correlated with the pathological finding. CONCLUSIONS: Although the high cost of PET makes its use as a screening test for all patients with augmented breasts unrealistic, it would be the best diagnostic choice if other methods failed.

Prognostic factors in 2230 Korean colorectal cancer patients: analysis of consecutively operated cases.

To define the prognostic factors in Korean colorectal cancer patients, univariate and multivariate analysis were performed on data from 2230 consecutive patients who underwent resection for colorectal cancer at the Seoul National University Hospital. The prognostic variables used for the analysis included patient's age, gender, bowel obstruction, bleeding, symptom duration, preoperative leukocyte count, preoperative serum carcinoembryonic antigen (CEA) level, Dukes' stage, tumor location, tumor size, depth of bowel wall invasion, number of lymph node metastases, histologic differentiation, and gross morphology of tumor. The overall 5-year survival rate was 62%. In the univariate analysis, all the factors except sex, symptom duration, and tumor size were associated with prognosis. Among the factors significant in the univariate analysis, Dukes' stage (p < 0.001), number of lymph node metastasis (p < 0.001), CEA level (p < 0.001), tumor location (p = 0.003), gross morphology of tumor (p = 0.017), and depth of bowel wall invasion (p = 0.031) were significant in the multivariate analysis. Several differences in prognostic factors between colon cancer and rectal cancer were observed. In the multivariate analysis, gross tumor morphology was significant only for colon cancer, and histologic differentiation was significant only for rectal cancer. Lymph node metastasis was an independent prognostic variable for both colon and rectal cancer, but its significance was more prominent for rectal cancer. Although Dukes' stage is the most reliable prognostic predictor, this study shows that other factors (preoperative CEA level, gross morphology of tumor, location of tumor, nodal status) also provide important information for the outcome of the patient.

Experience of 1446 rectal cancer patients in Korea and analysis of prognostic factors.

In order to investigate the changing pattern of rectal cancers in Korea and to identify prognostic factors, we investigated the case histories of 1446 rectal cancer patients who had received surgical treatment. During the study period there were trends toward a decrease in the ratio of rectal cancer to colon cancer, earlier detection (more Dukes' stages A and B and fewer C), a decrease in the number of abdominoperineal resections, and an increase in the number of sphincter-preserving operations. Univariate analysis of prognostic factors showed that gender, obstruction symptoms, preoperative serum carcinoembryonic antigen (CEA) level, tumor size, depth of bowel wall invasion, lymph node metastases (presence and number), tumor differentiation, operative method, and date of operation were significant, but age, symptom duration, and tumor location were not. The use of sphincter-saving operations did not adversely affect the clinical outcome. Multivariate analysis showed lymph node metastasis factor to be the most significant factor (P < 0.001); the depth of bowel wall invasion, differentiation, CEA level, and date of operation were also significant (0.001 < P < 0.05). This study shows that although anatomical extent of disease (depth of invasion and lymph node metastasis) is the most reliable prognostic predictor in rectal cancer, other factors such as preoperative CEA level and tumor differentiation also provide important information on the outcome and use of an anal-preserving operation does not adversely affect the patient survival.