Randomized, Multicenter, Phase III Trial of Heptaplatin 1-hour Infusion and 5-Fluorouracil Combination Chemotherapy Comparing with Cisplatin and 5-Fluorouracil Combination Chemotherapy in Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Heptaplatin (Sunpla) is a cisplatin derivative. A phase IIb trial using heptaplatin resulted in a 34% response rate with mild nephrotoxicity. We conducted a randomized phase III trial of heptaplatin plus 5-FU compared with cisplatin plus 5-FU in patients with advanced gastric cancer. MATERIALS AND METHODS: One hundred seventy-four patients (heptaplatin, n=88; cisplatin, n=86) from 13 centers were enrolled. The eligibility criteria were as follows: patients with pathologically-proven adenocarcinoma, chemonaive patients, or patients who had received only single adjuvant chemotherapy, and who had a measurable or evaluable lesion. On day 1, heptaplatin (400 mg/m2) or cisplatin (60 mg/m2) was given over 1 hour with 5-FU (1 gm/m2) on days 1~5 every 4 weeks. RESULTS: At the time of survival analysis, the median overall survival was 7.3 months in the 5-FU + heptaplatin (FH) arm and 7.9 months in the 5-FU + cisplatin (FP) arm (p=0.24). Of the FH patients, 34.2% (complete response [CR], 1.3%; partial response [PR], 32.9%) experienced a confirmed objective response compared with 35.9% (CR 0%, PR 35.9%) of FP patients (p=0.78). The median-time-to-progression was 2.5 months in the FH arm and 2.3 months in the FP arm. The incidence of neutropenia was higher with FP (28%) than with FH (16%; p=0.06); grade 3~4 nausea and vomiting were more frequent in the FP than in the FH arm (p=0.01 and p=0.05, respectively). The incidence of increased proteinuria and creatininemia was higher with FH than with FP; however, there was no statistical difference. There were no treatment-related deaths. CONCLUSION: Heptaplatin showed similar effects to cisplatin when combined with 5-FU in advanced gastric cancer patients with tolerable toxicities.

DNMT3b Promoter Polymorphism and Risk of Gastric Cancer in the Korean Population

PURPOSE: DNA methylation is an important epigenetic factor in tumorigenesis. We hypothesized that polymorphism of the promoter of the DNA methyltransferase 3b (DNMT3b) genes, which are responsible for regulating the methylation status of tumor suppressor genes, are associated with increased risk of gastric cancer. MATERIALS AND METHODS: In this hospital-based case-control study, to determine the role of this polymorphism of the promoter of DNA methyltransferase 3b (DNMT3b) genes in gastric cancer, we genotyped 176 cases and 70 control subjects. To determine the genotype, we used a polymerase chain reaction restriction fragment length polymorphism assay. We compared alleles and genotypes between the two groups and revealed an association of DNMT3b promoter polymorphism with increased risk of gastric cancer in the Korean population. RESULTS: Genotype frequencies were 14.8% (Cytosine-Cytosine), 71.6% (Cytosine-Thymine), and 13.6% (Thymine- Thymine) in the case patients and 40.0% (Cytosine-Cytosine), 42.9% (Cytosine-Thymine), and 17.1% (Thymine-Thymine) in the control subjects, respectively. Compared with CC homozygotes, CT heterozygotes had a 4.523-fold increased risk (OR, 2.13; 95% CI, 2.324~8.803), and the TT homozygotes had a 2.154-fold elevated risk (OR, 1.42; 95% CI, 0.899~5.165). For the T variant genotype (CT+TT), there was a 3.846-fold increased risk (OR, 1.88; 95% CI, 2.040~7.251). However, no significance was observed in the genotype distributions of both polymorphisms according to histopathology, stage of stomach cancer. The Ssame results were observed with Helicobacter infection. CONCLUSION: DNMT3b promoter polymorphism, especially the T variant genotype, is associated significantly with thean increased risk of gastric cancer.

Comparison of the Results in Gastric Carcinoma Patients undergoing Billroth I and Billroth II Gastrectomiesy

PURPOSE: The proper reconstruction technique to use after a distal subtotal gastrectomy for a gastric carcinoma, there has been a subject for debated what is the proper reconstruction technique. The aim of this study was to compare the gastric- emptying time and the quality of life following both B-I and B-II reconstructions after a distal gastrectomy for a gastric adenocarcinoma. MATERIALS AND METHODS: We studied 122 patients who had undergone a distal gastrectomy for a gastric adenocarcinoma between June 1999 and July 2002 at our hospital. 51 patients underwent B-I group, and 71 patients underwent B-II group. To evaluate the gastric-emptying time, we analyzed the T1/2 time by means of radionuclide scintigraphy using a gamma camera after ingestion of an (99m)Tc-tin-colloid steamed egg. The nutritional status was measured by the weight change. Postgastrectomy syndrome was evaluated using an abdominal symptoms survey. Dumping syndrome was measured using the Sigstad dumping score. RESULTS: The gastric-emptying time was somewhat delayed in the B-I group after a 6 month period, but there was no difference after 12 months between the two groups. There was less weight loss in the B-I group than in the B-II group (P=0.023). Fewer abdominal symptoms were occurred in the B-I group than in the B-II group. Dumping syndrome occurred less frequently in the B-I group than in the B-II group (P=0.013). CONCLUSION: In our study, the Billroth I reconstruction led to less weight loss, a better nutritional status, and a better quality of life than the Billroth II reconstruction. We concluded that after a distal subtotal gastrectomy, the Billroth I reconstruction would be considered when the procedure is oncologically suitable.

Clinical Characteristics and Prognosis of Gastrointestinal Stromal Tumors of Stomach

PURPOSE: Gastrointestinal stromal tumorsm (GISTs) are the most common mesenchymal tumors that arise anywhere in the tubular GI tract. The prognosis for GSTIs is important because f GISTs may metastasiwx in the liver or the abdominal cavity in an early stage. For the reason we examined the tumor size, the mitotic number, ki 67, p53, and c-kit mutation as independent prognostic factor for GISTs. MATERIALS AND METHODS: A retrospective study was conducted in 76 patients who had been re-evaluated for confirmation of diagnosis between Jan 1998 and Dec. 2001. at Catholic University of medicine. RESULTS: There were significant difference between the tumor size, mitotic indices, ki 67, c-kit mutations and the 5-years survival rates. Tumor size (> or = 5 cm) and mitotic index (> or = 5/50 HPF) were statistically related to a significantly poor prognosis (P=0.017 and P=0.042, respectively). c-kit mutations in exon 11 were found in 7 cases c-kit mutation was observed more frequently in high risk patients, and there was a significant difference between c-kit mutation and survival (P=0.037). Elevated ki 67 was noted in 34 out of the 76 cases. High risk patients showed elevated ki67 index more frequently and there was significant relation with the survival rate (P=0.0417). CONCLUSION: We think that tumor size, mitotic index, Ki 67 and c-kit mutation are as independent prognostic factors for GISTs, but more research is needed.

Value of Elevated Ki67 Index (>10%) and p53 Protein Expression as Prognostic Factors in GISTs

PURPOSE: Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors and express CD117, the prediction of their malignant potential remains difficult. The aim of this study is to evaluate the prognostic accuracy of elevated Ki67 index and p53 overexpression in combination with classical prognostic factors (tumor size and mitotic index). METHODS: A retrospective study was conducted in 84 patients who had been re-evaluated for confirmation of diagnosis based on immunohistochemical analysis with CD117 expression, between Jan 1991 and Dec 2001. Cases were classified as very low, low, intermediate and high-risk groups according to 2001 NIH consensus symposium. Elevated Ki67 index was assigned to the lesion that displayed 10% or more of immunoreactive cells. And p53 expression was assigned to the area with 5% or more of eosinophilic nucleus. RESULTS: Elevated Ki67 was noted in 37 (44.0%) out of 84 cases. High-risk patients showed elevated Ki67 index more frequently (P<0.0001) and there was significant relation between elevated Ki67 and survival rate (P=0.0417). The p53 expression was noted in 32 (38.1%) out of 84 cases. The p53 expression was significantly higher in high-risk patients (P=0.0081) than low-risk patients. But, there was no significant relation between p53 expression and survival rate. As a result of multivariate analysis, tumor size (P=0.0059), mitotic index (P=0.0016) and elevated Ki67 index (P=0.0384) were proved as significant independent prognostic factors. CONCLUSION: According to the results of our retrospective study, p53 expression is related to disease progression but its value as a prognostic factor in GISTs is uncertain. It is suggested that tumor size, mitotic rate and elevated Ki67 index are the helpful prognostic factors in GISTs.

Risk of the Gastric Cancer Associated with the Interleukin 1beta Gene Polymorphism and Helicobacter pylori

PURPOSE: According to the recent studies, it is shown that the polymorphism of Interleukin 1beta gene is associated with the incidence of gastric cancer caused by the Helicobacter pylori infection. Interleukin 1beta is a cytokine markedly inhibiting gastric acid secretion. Interleukin 1beta production associated with Helicobacter pylori gastric infection may exacerbate mucosal damage including chronic gastritis and atrophic gastritis, may induce eventual neoplasia. Among these Interleukin 1beta gene polymorphisms, polymorphisms at -31 portion and -511 portion may associated with these processes, eventually increase the risk of gastric cancer. We investigated the risk of gastric cancer according to the Helicobacter pylori infection and genetic polymorphism of Interleukin 1beta in gastric cancer patients. MATERIALS AND METHODS: 176 individuals with gastric cancer and 40 healthy controls were analyzed. Each group was divided into two groups whether they infected with Helicobacter pylori or not. DNA was extracted from the peripheral blood in all groups. The PCR-RFLP method was used for investigating the distribution of genotype of C/C, C/T, T/T at -31 portion and -511 portion. RESULTS: T/T genotype at -511 portion was 19.3% in gastric cancer cases and 10% in controls, which was statistically significant. (P=0.0432) The risk of gastric cancer was increased 4.86 (1.26~18.77) in group which had T/T genotype. In gastric cancer cases, C/C genotype at 31 portion was 27.6% in group with Helicobacter pylori infection and 12.8% in group without infection, which was statistically significant. (P=0.0047) The risk of gastric cancer was increased 4.82 (1.81~12.81) in group which had C/C genotype. CONCLUSION: T genotype at -511 portion among the Interleukin 1beta genetic polymorphisms may be the risk factor of gastric cancer. And, with Helicobacter pylori infection, C genotype at -31 portion may be the risk factor of gastric cancer.

Clinical Analysis for 30 Cases of Total or Subtotal Abdominal Colectomy and Total Proctocolectomy

PURPOSE: A total or a subtotal abdominal colectomy and a total proctocolectomy are performed occasionally for the surgical treatment of familial adenomatous polyposis, multiple colorectal cancers, ulcerative colitis, acute lower GI bleeding, and malignancy other than colorectal cancer. We studied 30 cases of patients who received either a total or a subtotal abdominal colectomy and a total proctocolectomy in one of the three hospitals affiliated with the Catholic University between January 1990 and December 2001. Our goal was to determine whether the total or subtotal abdominal colectomy and the total proctocolectomy are difficult and complicated procedures by comparing the mortality, the morbidity, the survival rate, and the complications to previously considered and reported results. METHODS: Thirty patients treated with either total or subtotal abdominal colectomy and with a total proctocolectomy from January 1990 to December 2001 were chosen for this study. Their gender, age, underlying diseases, family history, hospital days, symptoms, changes in defecation habits following the procedure, complications, mortality, survival rate, and relationship to malignancy were evaluated. RESULTS: Of the patients who received either total or subtotal abdominal colectomy and a total proctocolectomy, the average age was 44.6 years, the gender ratio was 1:1, and the underlying diseases were familial adenomatous polyposis (FAP) (43%), ulcerative colitis (UC) (20%), multiple colorectal cancers (17%), stomach cancer (7%), and Crohn's disease (3%). Diarrhea and rectal bleeding were the most common clinical symptoms, and abdominal pain and intestinal obstruction were frequently observed. A total proctocolectomy (TPC) with permanent ileostomy was the most frequently performed procedure (47%), and a TPC with ileoanal anastomosis was done in 10% of the cases. A total abdominal colectomy (TAC) with ileorectal anastomosis was applied in 23% of the cases, and subtotal abdominal colectomy (sTAC) with ileosigmoidal anastomosis was done in 20% of the cases. The operative mortality rate was 3% as one patient among thirty died. Postoperative complications developed in 33% of the patients. FAP and UC patients without cancer (45%) survived for over 4 or 5 years, but FAP and UC patients with cancer, especially an adenocarcinoma, survived for only 2.5 years. CONCLUSIONS: A total or subtotal abdominal colectomy (TAC or sTAC) and a total proctocolectomy (TPC) are appropriate procedures with low mortality, low morbidity, and a low complication rate for several kinds of diseases. A TPC with ileorectal anastomosis is the procedure of choice for sparing the rectum in FAP and UC patients without coexisting cancer and without mutation of the APC gene after codon 1250, but a TPC with ileoanal anastomosis is recommended if there is a mutation of the APC gene after codon 1250. A TPC with ileostomy is the preferred method for FAP and UC patients with coexisting cancer.

Clinical Analysis of Perforated Gastric Cancer

PURPOSE: Generalized peritonitis caused by a free perforation of gastric cancer is a rare condition, which occurs in 1~4% of all gastric cancer patients. To assess the characteristics of the patients and investigate the optimal treatment of choice, the data from 51 patients previous recent 10 years were retrospectively analyzed. METHODS: Between 1988 and 1997, 51 patients underwent surgical treatment for perforated gastric cancer. The clinicopathological features and survival rates of the resected group (n=39) and the non-resected group (n=12) were analyzed. RESULTS: The incidence was 0.78% and the mean age was 57 years. The most common tumor location was in the lower 1/3 in the resected group (n=21, 53.8%) and in the upper 1/3 in the non-resected group (n=6, 50%). Borrmann type 3, the poorly differentiated type, and a positive serosa invasion were more common in both groups. Liver and peritoneal metastases were observed in 2 cases (5.2%) and 7 cases (14.3%) in the resected group, and 4 cases (33.4%), and 3 cases (25%) in the non-resected group, respectively. Resectability found in 76.5%: 27 cases of a subtotal gastrectomy and 12 cases of a total gastrectomy. A limited lymph node dissection (D0, D1) was performed in 14 cases (35.9%) and an extended dissection (D2, D3) was performed in 25 cases (64.1%). The 5-year survival rate of stage I was 80%, 40% in stage II, 14% in stage III and 0% in stage IV, and the overall 5 year survival rate was 20.5% in the resected group and 0% in the non-resected group. The depth of invasion, lymph node metastasis and tumor stage significantly influenced the survival rate of the patients. CONCLUSION: Because a perforation of the gastric cancer may develop in every stage, surgeons must take care of these patients by the same way as with non-perforation cases.

Three Cases of Biliary Cystadenoma and Biliary Cystadenocarcinoma

A biliary cystadenoma and a cystadenocarcinoma are rare intrahepatic cystic neoplasm. The clinical feature is not marked but abdominal fullness and mass are the most common symptoms. The tumor is commonly a large multilocular cystic mass which requires hepatectomy for cure. We experienced one case of biliary cystadenoma and two cases of biliary cystadenocarcinoma. The biliary cystadenoma case was a 58-year-old female with right upper quadrant discomfort for 5 months and a 17 cm sized multilocular cystic mass. The serum CA 125 level was elevated but returned to normal level after resection. A right hepatectomy was performed and the patient has had no recurrence for 14 months after the resection. One of the biliary cystadenocarcinoma cases was a 42-year-old man with a 12 cm sized multilocular cystic mass in the right upper quadrant of his abdomen. A right hepatectomy was performed and the patient has had no recurrence for 12 months after the resection. The other biliary cystadenocarcinoma case was a 70-year-old man with right upper quadrant pain and a 5 cm sized cystic mass. A left hepatecomy was performed and the patient has had no recurrence for 8 month after the resection. The treatment of choice for a biliary cystadenoma or cystadenocarcinoma is complete resection. We report three cases of biliary cystadenoma and cystadenocarcinoma with a review of the literature.

Detection of Micrometastases in the Sentinel Lymph Node from Patients with Early Gastric Cancer

PURPOSE: If the SLN (sentinel lymph node) is an accurate predictor of the lymph node status it should eliminate unnecessary lymph node dissection, resulting in a lower morbidity and mortality in patients with an early gastric cancer. The aim of this study was to investigate the feasibility of SLN biopsy for its location, accuracy and ability to sensitize the tumor cell detection, using reverse transcriptase-polymerase chain reactions (RT-PCR) for the cytokeratin 19 and CD44 variants. METHODS: SLN biopsies were performed in patients with early gastric cancer (n=33). After a gastrectomy to the apposite site, isosulfan blue dye (0.5-1.0 ml) was injected submucosal medially, laterally, superiorly and inferiorly, adjacent to the tumor site. Lymphatic channels were immediately apparent. Sentinel nodes were separately submitted, and evaluated with RT-PCR, using the cytokeratin 19 and CD44 variants. Following the removal of the sentinel node, the adjacent regional nodes were also removed. Both SLN and non-SLN were examined with H&E stain and RT- PCR. RESULTS: Sentinel nodes could be identified in 26 of 33 patients (79%). The average number of sentinel nodes detected was 1.4 and were chiefly perigastric nodes. Of these 26 patients, 6 had micrometastasis in their sentinel nodes by RT-PCR detection using the cytokeratin 19 and CD44 variants. The specificity of the SLN status in the diagnosis of the lymph node status was 95% (20/21). One patient (4%) had skip metastasis. CONCLUSION: A SLN biopsy, using indocyanine green, can be performed with a high success rate. A focused examination of the sentinel nodes detected by indocyanine green with RT-PCR will resolve the underestimation of micrometastasis in regional lymph nodes, and improve the accuracy of the pathological staging. If the sentinel node concept is clinically feasible for early gastric cancer, we would perform not only accurate staging, but also effective surgical treatment, with minimally invasive techniques.

A clinical analysis of 50 cases of renal transplantation / 대한이식학회지

No abstract available.