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Background/aim Claudin18.2 (CLDN18.2) is a tight junction protein that has been identified as a promising target in gastric cancer. This study aimed to evaluate the clinical relevance of CLDN18.2 expression in gastric cancer. Patients and methods This study included 367 patients diagnosed with gastric cancer, who underwent curative surgical resection. Immunohistochemical staining for CLDN18.2 was carried out, and expression was scored semi-quantitatively, based on staining intensity and the percentage of staining. Results CLDN18.2 expression was observed in 273 patients (74.4%), and 108 (29.4%) were classified as CLDN18.2-positive by predefined criteria. CLDN18.2 expression was not correlated with age, sex, tumor location, or stage. Expression rates were higher in diffuse-type and HER2-positive tumors. In multivariate survival analysis, CLDN18.2 expression was not associated with survival outcomes. Conclusion Higher expression of CLDN18.2 was observed in diffuse-type and HER2-positive gastric cancers. Meanwhile, CLDN18.2 expression was not associated with survival in patients with gastric cancer.

Totally laparoscopic distal gastrectomy (TLDG) frequently involves the use of delta shaped gastroduodenostomy (DSG) for intracorporeal anastomosis. However, DSG has some drawbacks, and the book binding technique (BBT) was developed as a new technique to overcome these drawbacks. Subsequently, this technique was further improved with the development of modified book binding technique (MBBT). This study evaluated the safety and feasibility of MBBT in patients undergoing TLDG. Thirty-three patients who underwent TLDG with MBBT were retrospectively evaluated. The mean operation time was 277.6±37.1 minutes, including 51.9±15.7 minutes for reconstruction. Two patients had anastomosis-related complications, one patient with stricture after leakage and 1 patient with stenosis. The former patient was treated with endoscopic balloon dilatation, and the latter was managed conservatively; neither required re-operation. MBBT is a safe and feasible technique, with acceptable surgical outcomes. It may be a good alternative option for the treatment of intracorporeal anastomosis in patients undergoing TLDG.

In this paper, a novel time-domain measurement technique on a high parallelism probe card with protection resistors installed is proposed. The measured signal amplitude decreases when the measurement is performed by Needle Auto Calibration (NAC) probing on a high parallelism probe card with installed resistors. Therefore, the original signals must be carefully reconstructed, and the compensation coefficient, which is related to the number of channel branches and the value of protection resistors, must be introduced. The accuracy of the reconstructed signals is analyzed based on the varying number of channel branches and various protection resistances. The results demonstrate that the proposed technique is appropriate for evaluating the overall signal performance of probe cards with Automatic Test Equipment (ATE), which enhances the efficiency of probe card performance test dramatically.

A 58-year-old woman, who had undergone total gastrectomy for early gastric cancer 9 years previously, visited the outpatient clinic complaining of progressive difficulty in walking for 15 d. Laboratory examinations showed macrocytic anemia and a decreased serum vitamin B12 concentration and increased serum concentrations of folate, vitamin E and copper. Magnetic resonance imaging showed multifocal high signal intensities along the posterior column of the cervical and thoracic spinal cord. Treatment consisted of intramuscular injections of vitamin B12 for 7 d, which increased her serum level of vitamin B12 to normal. This was followed by weekly intramuscular injections of vitamin B12 for another 2 wk and oral administration of vitamin B12 three times per day. After comprehensive rehabilitation for 4 wk, she showed sufficient improvements in strength and ataxic gait, enabling her to return to her normal daily activities.

Introduction Potential challenges associated with immediate small breast reconstruction include an inadequate size of the donor site, a thinner skin envelope and limited selection of implants. We present immediate postmastectomy reconstruction of small breasts with a laparoscopically harvested pedicled omental flap (LHPOF) in five Korean women. Methods From December 2014 to July 2015, we performed immediate postmastectomy reconstruction with an LHPOF in five breast cancer patients. Data on the patients’ age; body mass index; tumour size; site, type and weight of the mastectomy specimen; operative time; hospital stay; complications; postoperative chemotherapy or radiation therapy; and follow-up duration were reviewed in this retrospective clinical study. Results The mean mastectomy specimen weight was 212 g (range: 104–272 g). The mean operative time was 298 min (range: 240–380 min), and the mean harvesting time was 75 min (range: 65–90 min). There were no flap-related complications such as fat necrosis or flap loss and no donor site-related complications such as bowel dysfunction, an epigastric bulge or hernia during the follow-up period (average: 8.2 months, range: 5–11 months). The cosmetic results were satisfactory. Discussion The LHPOF can be useful for immediate postmastectomy reconstruction of small breasts, because it provides a soft and naturally ptotic appearance of the reconstructed breast (versus implant-based reconstruction) with low donor-site morbidity (versus other autologous tissue reconstruction approaches).

Purpose: The aim of this study was to compare ESD only and subsequent Laparoscopy-assisted gastrectomy (LAG) patients for EGC through propensity score matching analysis. Methods: This study was a retrospective review of the records of 46 consecutive patients with gastric cancer who underwent LAG after ESD from 2009, September to 2014, September, and propensity matching analysis was performed with 92 patients who underwent LAG without ESD as a control group. Subgroup analysis was performed with the interval of subsequent laparoscopic gastrectomy and endoscopic resection (within 2 weeks, 2~4 weeks, above 4 weeks). Results: There were no significant differences in age, gender, body mass index, comorbidity, previous abdominal surgery, and location of the lesion or clinical stage between the two groups. Early postoperative outcomes including postoperative complications and postoperative hospital stay were not significantly different between the two groups. According to subgroup analysis with the interval of laparoscopic gastrectomy and endoscopic resection, there were no significant differences in early outcomes in three groups. However, only early postoperative complication rate was significantly higher in patients who received LAG more than 4 weeks after ESD (0 versus 4.76 versus 40 per cent; p=0.0032). Conclusion: We analyzed the influence of ESD on subsequent LAG using propensity score matching to reduce the bias. However, we found that ESD might induce inflammation for a significant duration, but ESD had little influence on early postoperative outcome of LAG.

Aims Adjuvant chemotherapy is recommended for gastric cancer after a gastrectomy with D2 dissection. However, its survival benefit in elderly patients is unclear. Here we investigated the use of adjuvant chemotherapy in patients ≥70 years old with stage II or III gastric cancer. Methods Patients ≥70 years old diagnosed with stage II or III gastric cancer at Ulsan University Hospital were identified. A retrospective analysis of electronic and paper patient records was performed. Results From 2008 to 2012, 277 patients ≥70 years old underwent gastrectomy with D2 dissection. Of these patients, 94 were pathologically diagnosed with stage II or III; 55 of these patients (58.5%) received adjuvant chemotherapy and 39 received regular checkups without chemotherapy. Fluoropyrimidine-alone regimens, including TS-1 composed of tegafur, gimestat and otastat potassium (n = 26) and doxifluridine (n = 22), were more commonly used than fluoropyrimidine-platinum combination regimens (n = 7). With a median follow-up of 30.9 (range 0.8–65.5) months, the median relapse-free survival of patients with adjuvant chemotherapy or regular follow-up only was 35.5 and 20.4 months, respectively (P = 0.030). Multivariate analysis revealed that adjuvant chemotherapy is associated with longer relapse-free survival (hazard ratio 0.50; 95% confidence interval 0.27–0.96). There was a trend toward an improved overall survival in the adjuvant chemotherapy group compared with the follow-up only group (P = 0.242). Conclusions Although well-designed prospective studies are required, adjuvant chemotherapy may confer a potential survival benefit in elderly patients (aged 70 or older) with stage II or III gastric cancer after a gastrectomy with D2 dissection.

Purpose: Mesh non-fixation in TEP is associated with lower cost and shorter operative time, and it is safe and recommended when performed by an experienced surgeon. In performance of TEP surgery using a non-fixation mesh, particularly by a non-experienced surgeon, prevention of mesh migration is an important issue for mesh application. The aim of this study was to report on a fixation method using a non-preformed mesh encircling a cord structure without the use of tacks, staples, or fibrin sealants in TEP surgery. Methods: A total of 41 patients who had undergone mesh-encircling TEP without fixation from December 2008 (first case of surgery) to June 2012 were analyzed. Results: The mean follow-up period was 23.2 months (12~35 months). Three patients complained of scrotal discomfort, and one patient complained of scrotal edema, but they were resolved with conservative management. There was no recurrence during the follow up period. Conclusion: The method of mesh-encircling TEP without fixation material and no additional mesh in which the slit of the mesh is wrapped around the cord structure using an overlay suture is a simple and safe technique without compromising recurrence or chronic pain.

The limited donor organ supply is a main problem for transplant surgeons in Korea, and forces them to use organs from extended sources. In one such case, we reused a transplanted kidney allograft in August 2012. This was the first successful case involving the reuse of a transplanted kidney allograft in Korea. The kidney donor was a 44-year-old man brain-dead due to spontaneous subdural hemorrhage. He received a kidney transplant from his sister in 2006. The second recipient was a 59-year-old man who had been receiving hemodialysis for 11 years. There were full human leukocyte antigen (HLA) matches between the first donor and the first recipient, and two HLA mismatches between the first donor and the second recipient. Fortunately, we were able to perform a crossmatch test between the first donor and the second recipient as well as the first recipient and the second recipient (with the first donor’s agreement). We used the left iliac artery for perfusion instead of the aorta during organ procurement. The cold ischemic time was 4 hours and the initial kidney function was excellent. The patient has been doing well, without any significant complications or rejections, for 3 weeks. His last serum creatinine level was 0.91 mg/dL. Our case shows that the reuse of kidney allografts could be a possible solution for the shortage of donor kidneys. However, this method requires careful consideration and an agreement among participants before its performance.

Purpose: Laparoscopy-assisted distal gastrectomy (LADG) has gained wide acceptance for minimally invasive treatment of early gastric cancer (EGC). The aim of this study was to see the relationship between the operative approach of a distal subtotal gastrectomy and food retention of the remnant stomach. Methods: A retrospective review of the records of 321 consecutive patients with gastric cancer who underwent a distal subtotal gastrectomy between 2001 and 2008 was conducted. A total of 233 patients who revisited the same surgeon’s outpatient clinic and received regular endoscopic examination using the same protocol were finally included in this study. Reconstruction was performed using the Billroth I procedure. Mechanical-stapled anastomosis (MSA) was performed in 112 patients and conventional hand-sutured anastomosis (HA) was performed in 121 patients. Results: According to results of multivariate analysis, the anastomosis method (MSA) was the only independent risk factor for accumulation of food residue. At six and 12 months after surgery, the incidence of food retention was higher in patients who had undergone MSA (22.3%, 13.4%) than in those who had undergone HA (9.1%, 2.5%) (p=0.006, p=0.002, respectively). However, the incidence of food residue at 24 months after surgery did not differ statistically between MSA and HA (p=0.266). Conclusion: Our results showed that the laparoscopic approach was not influenced on the accumulation of food residue. Mechanical-stapled anastomosis was the only independent risk factor for food retention. During the early postoperative period, although more food retention was observed in patients who underwent MSA than in those who underwent HA, in the long term, this anastomosis method did not influence food retention after a distal gastrectomy.

Potential challenges associated with immediate small breast reconstruction include an inadequate size of the donor site, a thinner skin envelope and limited selection of implants. We present immediate postmastectomy reconstruction of small breasts with a laparoscopically harvested pedicled omental flap (LHPOF) in five Korean women.From December 2014 to July 2015, we performed immediate postmastectomy reconstruction with an LHPOF in five breast cancer patients. Data on the patients' age; body mass index; tumour size; site, type and weight of the mastectomy specimen; operative time; hospital stay; complications; postoperative chemotherapy or radiation therapy; and follow-up duration were reviewed in this retrospective clinical study.The mean mastectomy specimen weight was 212 g (range: 104-272 g). The mean operative time was 298 min (range: 240-380 min), and the mean harvesting time was 75 min (range: 65-90 min). There were no flap-related complications such as fat necrosis or flap loss and no donor site-related complications such as bowel dysfunction, an epigastric bulge or hernia during the follow-up period (average: 8.2 months, range: 5-11 months). The cosmetic results were satisfactory.The LHPOF can be useful for immediate postmastectomy reconstruction of small breasts, because it provides a soft and naturally ptotic appearance of the reconstructed breast (versus implant-based reconstruction) with low donor-site morbidity (versus other autologous tissue reconstruction approaches).

A 58-year-old man underwent laparoscopy-assisted distal gastrectomy (LADG) with Billroth I gastroduodenostomy due to early gastric cancer. During surgery, the perigastric vessels were ligated with Hem-o-Lok clips. Esophagogastroduodenoscopy (EGD) 6 months later showed a fungating mass at the anastomosis site. Repeat EGD 1 year after LADG showed a Hem-o-Lok clip at the fungating mass lesion. Because the patient was asymptomatic, with no major abnormalities on clinical examination, and endoscopic removal of the clip would have been difficult due to the presence of adhesions and inflammation, no attempt was made to remove the clip. The patient remained well after the exposed Hem-o-Lok clip was identified. A third EGD 6 months later showed that the clip had disappeared from the anastomosis site, and that this site was covered with normal mucosa surrounding the scar.

PURPOSE To evaluate the effectiveness of endoscopic submucosal resection with a ligation device (ESMR-L) on histologic complete resection for the treatment of small rectal carcinoid tumors in comparison with the treatment with endoscopic mucosal resection (EMR) alone. METHODS Thirty-five patients with small rectal carcinoid tumors were enrolled prospectively for ESMR-L, and we retrospectively reviewed 74 carcinoid tumor patients who underwent EMR. The comparison between ESMR-L and EMR groups was analyzed including endoscopic and histologic complete resection and complications after resection. We also evaluated the associations of histologic complete resection with clinical and procedure-related factors. RESULTS The histologic complete resection rate was significantly higher in ESMR-L than in EMR (94.3% vs. 75.7%, P=0.019). In addition, the resection time was significantly shorter in ESMR-L than in EMR (4.16±1.48 min vs. 5.11±2.47 min, respectively, P=0.014). Moreover, previously biopsied rectal carcinoid tumors were significantly associated with histologic incomplete resection, especially in patients who underwent EMR (odds ratio, 6.28; 95% confidence interval, 1.92-20.58; P=0.002). CONCLUSIONS Compared with EMR, ESMR-L is a safe and effective method for histologic complete resection of small rectal carcinoid tumors, especially in patients with previously biopsied carcinoid tumors.

Severe sepsis and septic shock caused mainly by bacterial infections are life-threatening conditions that urge the development of novel therapies. However, host responses to and pathophysiology of sepsis have not been clearly understood, which remains a major obstacle for the development of effective therapeutics. Recently, we have shown that stimulation of a costimulatory molecule, CD137, enhanced survival of mice infected with the Gram-positive (G + ) intracellular bacterium Listeria monocytogenes but decreased survival in a polymicrobial sepsis model. Herein, we report that CD137 deficiency or blocking of CD137 signaling decreased antibacterial responses of mice infected with G + bacteria ( Staphylococcus aureus , Streptococcus pneumoniae , and Enterococcus faecalis ) but increased these responses in mice infected with Gram-negative (G − ) bacteria ( Escherichia coli , Pseudomonas aeruginosa , and Salmonella enterica serovar Typhimurium). Consistent with these findings, stimulation of CD137 by administration of agonistic antibody enhanced responses against G + bacteria, whereas it decreased these responses against G − bacteria. Neutrophils were responsible for CD137-mediated opposite roles in control of G + and G − bacterial infections. Stimulation of CD137 enhanced activities of neutrophils against S. aureus but decreased these activities against E. coli , while CD137 blocking produced opposite results with the stimulation of CD137 in vivo and in vitro . Furthermore, we found that combined signaling of CD137 and Toll-like receptor 2 (TLR2) induced synergistic production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) by neutrophils, but combined signaling of CD137 and TLR4 did not. Our data strongly suggest that CD137 may play a dual role in sepsis in association with TLRs.

Objective KAI1 COOH-terminal interacting tetraspanin (KITENIN) contributes to tumor invasion and metastasis in various cancers. The aim of this study was to investigate expression of KITENIN in patients with oral cavity squamous cell carcinoma (SCC) and to determine whether KITENIN affects tumor cell behavior in oral cavity SCC cell line. Methods Western blotting and immunohistochemistry was used to assess alteration of KITENIN expression in human oral cavity SCC and normal oral cavity mucosa. To evaluate the impact of KITENIN knockdown, the cell invasion assay and cell migration assay using small-interfering RNA were performed. Results KITENIN protein expression was significantly increased in human oral cavity SCC tissues than in normal oral cavity mucosa by Western blotting. KITENIN immunoreactivity was strongly identified in human oral cavity SCC relative to adjacent normal tissue. Knockdown of KITENIN resulted in significantly reduced cell invasion in human oral cavity SCC cells (p = 0.001). Cell migration showed a marked decrease in KITENIN knockdown oral cavity SCC cells compared to the negative control oral cavity SCC cells (p = 0.01). Conclusion KITENIN is associated with tumor invasiveness and metastasis in human oral cavity SCC.

The development of gastric cancer (GC) is closely related to chronic inflammation caused by Helicobacter pylori infection, and herpes virus entry mediator (HVEM) is a receptor expressed on the surface of leukocytes that mediates potent inflammatory responses in animal models. However, the role of HVEM in human GC has not been studied. Previously, we showed that the interaction of HVEM on human leukocytes with its ligand LIGHT induces intracellular calcium mobilization, which results in inflammatory responses including induction of proinflammatory cytokine production and anti-bacterial activities. In this study, we report that leukocytes from GC patients express lower levels of membrane HVEM (mHVEM) and have lower LIGHT-induced bactericidal activities than those from healthy controls (HC). In contrast, levels of soluble HVEM (sHVEM) in the sera of GC patients were significantly higher than in those of HC. We found that monocyte membrane-bound HVEM is released into the medium when cells are activated by proinflammatory cytokines such as TNF-α and IL-8, which are elevated in the sera of GC patients. mHVEM level dropped in parallel with the release of sHVEM, and release was completely blocked by the metalloprotease inhibitor, GM6001. We also found that the low level of mHVEM on GC patient leukocytes was correlated with low LIGHT-induced bactericidal activities against H. pylori and S. aureus and production of reactive oxygen species. Our results indicate that mHVEM on leukocytes and sHVEM in sera may contribute to the development and/or progression of GC.

Although genetic factors are a well-known cause of colorectal cancer, environmental factors contribute more to its development. Despite advances in the fields of surgery, radiotherapy and chemotherapy, the cure rates for colon cancer have not substantially improved over the past few decades. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the principal pungent ingredient of hot chili pepper, has exhibited an anti-tumor effect in many cell types. However, the mechanisms responsible for the anti-tumor effect of capsaicin are not yet completely understood. In this study, we investigated whether capsaicin induces apoptosis in colon cancer cell lines. Capsaicin decreased cell viability in a dose-dependent manner in Colo320DM and LoVo cells. In addition, capsaicin produced cell morphology changes and DNA fragmentation, decreased the DNA contents, and induced phosphatidylserine translocation, which is a hallmark of apoptotic cell death. We showed that capsaicin-induced apoptosis is associated with an increase in ROS generation and a disruption of the mitochondrial transmenbrane potential. A possible mechanism of capsaicin-induced apoptosis is the activation of caspase 3, a major apoptosis-executing enzyme. Treatment with capsaicin induced a dramatic increase in caspase 3 activity, as assessed by the cleavage of Ac-DEVD-AMC, a fluorogenic substrate. In conclusion, our results clearly showed that capsaicin induced apoptosis in colon cancer cells. Although the actual mechanisms of capsaicin-induced apoptosis remain uncertain, it may be a beneficial agent for colon cancer treatment and chemoprevention.

Hepatocellular carcinoma (HCC) is a so highly invasive tumor that metastasizes hematogenously and lymphogenously to distant site. Frequent sites are lung, regional lymph node, bone, and adrenal gland. But metastasis to the gastrointestinal (GI) tract is rare, and most common site is stomach. Metastasis to the small intestine is extremely rare. Moreover, metastatic HCC of the small bowel causing intussusception has not been reported until now. Here, we report a case of metastasis of HCC to the small bowel manifested by intussusception.

Schwannoma, which arises from the neural sheath of peripheral nerves, is the most common benign tumor in the retroperitoneum in adults. Complete excision is the treatment of choice for retroperitoneal schwannoma. During surgery, it seems to be unnecessary to identify the small peripheral nerve from which it develops. Keeping a dry field, however, through meticulous control of fine vasculature is of primary importance to avoid inadvertent injury to any of the adjacent organs, large vessels or important nerves. There are few vessels, if any, on the anterior and lateral surfaces of the tumor. Numerous small vessels to and from the tumors are located at its posterior and medial (aortic) aspects, without forming large trunks. Harmonic scalpel may be a good armamentarium in this area. In conclusion, considering such multiple small tumor vessels running adjacent to the aorta, the surgeon should pay close attention to the course of central dissection of these tumors in the retroperitoneum.

BB, a member of the TNF receptor superfamily, functions mainly as a costimulatory molecule in T cells. Since signaling through 4-1BB provides T cells with costimulation independently of CD28, it has been postulated that 4-1BB plays an important role in allograft rejection. In this study, we demon- strated the critical role of 4-1BB in heart allograft rejection using 4-1BB-deficient mice. When 4-1BB- deficient C57BL/6 mice received MHC-mis- matched cardiac transplant of Balb/c origin, there was a markedly-delayed graft rejection as com- pared with the wild type. The delayed graft rejec- tion in the mutant mice correlated with less severe lymphocytic infiltration and vasculitis in the donor hearts. The cardiac grafts were harvested on days 1,3, 5, and 7, and the transcription level of various T cell cytokines and antigens were analyzed by RT- PCR. Furthermore, T cells of 4-1BB-deficient mice showed lower proliferation and cytokine produc- tion when challenged with allostimulatory den- dritic cells. We found that the mRNA levels of FasL and T cell activation cytokines such as IL-2, IFN-y, iNOS were decreased in 4-1BB-/- mice compared to wild type mice. Whereas, transcription of B7-2 antigen, CD28 related costimulatory molecule, was increased in 4-1BB/- mice. These findings have a clinical implication that the blockade of 4-BB sig- naling may prolong the survival of solid organ transplants.

117 Background: Adjuvant chemotherapy for gastric cancer after gastrectomy with D2 dissection can be recommended. However, there are limited data of survival benefit in the elderly. We sought to investigate the use of adjuvant chemotherapy for patient ≥70 years old with stage II or III gastric cancer and identify its impact on survival. Methods: Patient ≥70 diagnosed with stage II or III gastric cancer at the Ulsan University Hospital from 2008-2012 were identified. A retrospective analysis of electronic and paper patient records was performed to identify baseline characteristics, chemotherapy used, toxicity, and survival. Results: A total of 277 patients ≥70 years old underwent gastrectomy with D2 dissection from 2008-2012. Of these, 94 patients were pathologically diagnosed as stage II or III gastric cancer. Among the 94 patients, 58.5% of patients (n=55) received adjuvant chemotherapy and 39 patients received regular check-up without chemotherapy. Fluoropyrimidine alone regimens including TS-1 (n=26) and Didox (n=22) were more commonly used compared with fluroropyrimidine-platinum combination regimens (n=7). With median follow-up of 30.9 (range, 0.8-65.5 months), the median relapse-free survival (RFS) of patients with adjuvant chemotherapy or regular follow-up only was 39.1 and 26.1 months (P = 0.027). Multivariate analysis revealed that the adjuvant chemotherapy was associated with longer RFS (hazard ratio 0.51; 95% confidence interval 0.27 – 0.98). There was a trend toward improved overall survival (OS) in the adjuvant chemotherapy group, with a median OS of 51.2 months compared with that of 44.5 months in the regular follow-up only group (P= 0.242). Toxicities in adjuvant chemotherapy were generally tolerated. Conclusions: In elderly patients (aged 70 or older) with stage II or III gastric cancer after gastrectomy with D2 dissection, adjuvant chemotherapy may carry a potential survival benefit for those who receive it. Further well-designed prospective studies are needed to confirm these finding.

76 Background: Despite a continuing debate on the role of adjuvant chemotherapy, several studies have suggested that mitomycin-C (M) plus fluoropyrimidine (f) could improve the outcome of curatively resected advanced gastric cancer (AGC) patients (pts). To improve further the adjuvant Mf chemotherapy, we have prolonged the administration of oral fluoropyrimidine (F) and added cisplatin (P) to Mf (MFP) and performed a phase III randomized trial to determine whether this strategy could improve the 3-year relapse free survival (3yRFS) in curatively resected AGC pts (HR=0.63, α=0.05, β=0.1). Three year follow-up results were reported in 2008 ASCO meeting. Here we report long-term follow-up results for confirmation. Methods: Three to 6 wks after R0 resection, the pts who had postoperative stage II-IV were randomized to receive either Mf or MFP adjuvant chemotherapy. For Mf group, 20 mg/m2 of M was iv injected and 4 wks later, 460-600 mg/m2/day of doxifluridine was administered orally for 3 months. For MFP group, the administration of doxifluridine was extended for a total of 12 months and 6 shots of monthly 60 mg/m2 of cisplatin were added to Mf. Results: Between Feb 2002 and Aug 2006, a total of 871 pts were randomized (435 in Mf, 436 in MFP). Sixteen pts were excluded because of ineligibility (11 in Mf, 5 in MFP). Postoperative stages were II in 51.0%, IIIA in 31.1%, IIIB in 9.4%, and IV in 8.5% of pts. With a median follow up of 6.6 yrs in April 2011, a total of 353 events (relapse or death) have been observed. There was no difference in RFS between the two groups (HR, 1.10; 95% C.I. 0.89 – 1.35; p=0.3918; 5yRFS 61.1% in Mf and 57.9% in MFP). Difference in overall survival (OS) was also insignificant (HR, 1.11; 95% C.I. 0.89 – 1.39; p=0.3349; 5yOS 66.5% in Mf and 65.0% in MFP). Conclusions: Long-term follow-up results of AMC 0201 trial confirmed prolongation of doxifluridine administration and addition of cisplatin to adjuvant chemotherapy with mitomycin-C plus 3 months of doxifluridine did not improve the treatment outcome in curatively resected AGC pts.

Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.

The matrix metalloproteinases (MMPs) have been associated with tumor cell invasion and metastasis of human cancers by mediating the degradation of extracellular matrix components. Therefore, these enzymes and their inhibitor (TIMP-2) constitute promising targets in the development of anticancer therapies. In order to investigate the correlation between expressions of TIMP-2, MMPs and clinical outcome, immunohistochemical staining of MMP-2, MMP-9, and TIMP-2 were performed on paraffin-embedded tissue sections of 15 early gastric cancers (EGC) and 15 advanced gastric carcinomas (AGC) without nodal metastasis and 15 AGC with nodal metastasis (AGCn+). MMP-2 and MMP-9 were expressed in neoplastic cell plasma membrane in 83.3% and 88% of cases of AGC, respectively with inter-tumoral variability of staining intensity. MMP-2 and MMP-9 staining were not correlated with presence of nodal metastasis or degree of invasion depth at the time of diagnosis (p>0.05). The immunoreactivity of TIMP-2 was detected in the peri-tumoral stroma. Residual benign stomach tissue showed no or weak immunoreactivity for TIMP-2 staining. Among AGC, neoplasms with diffuse and strong TIMP-2 staining have less frequent metastasis (28.6%) than cases with focal and weak (68.8%) (p

Heat shock protein (Hsp) in tumor cells has been proposed to enhance their resistance to chemotherapeutic agents. In the present study, we investigated the influence of Hsp expression on the irinotecan resistance of human colorectal cancer cells. Among eight Hsp genes tested in this study, we confirmed that the expression of Hsp27 correlated with irinotecan resistance in colorectal cancer cells. Specific inhibition of Hsp27 expression using an antisense oliogodeoxynucleotide increased the irinotecan sensitivity. On the contrary, an overexpression of Hsp27 decreased the irinotecan sensitivity in colorectal cancer cells. Elevated expression of Hsp27 decreased caspase-3 activity in colorectal cancer cells. The expression level of Hsp27 determined by immunohistochemical analysis correlated with the clinical response to irinotecan in colorectal cancer patients. Hsp27 expression levels of irinotecan-non-responder (mean staining score, 6.28; proportion of high staining score, 64.2%) were significantly higher compared to those of irinotecan-responder (mean staining score, 3.16; proportion of high staining score, 33.3%) (P for t-test=0.045). These findings suggest that Hsp27 is involved in the irinotecan resistance of colorectal cancer cells possibly by reducing caspase-3 activity.