Gyu Yeol Kim

Heat shock protein 27 is associated with irinotecan resistance in human colorectal cancer cells

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.

Combination Chemotherapy with 5-Fluorouracil and Heptaplatin as First-line Treatment in Patients with Advanced Gastric Cancer

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.

Bacteriology and Changes in Antibiotic Susceptibility in Adults with Community-Acquired Perforated Appendicitis

This study evaluated bacterial etiology and antibiotic susceptibility in patients diagnosed with community-acquired perforated appendicitis over a 12-year-period. We retrospectively reviewed records of adult patients diagnosed with perforated appendicitis at an 800-bed teaching hospital between January 2000 and December 2011. In total, 415 culture-positive perforated appendicitis cases were analyzed. Escherichia coli was the most common pathogen (277/415, 66.7%), followed by Streptococcus species (61/415, 14.7%). The susceptibility of E. coli to ampicillin, piperacillin/tazobactam, ceftriaxone, cefepime, amikacin, gentamicin, and imipenem was 35.1%, 97.1%, 97.0%, 98.2%, 98.9%, 81.8%, and 100%, respectively. The overall susceptibility of E. coli to quinolones (ciprofloxacin or levofloxacin) was 78.7%. During the study period, univariate logistic regression analysis showed a significant decrease in E. coli susceptibility to quinolones (OR = 0.91, 95% CI 0.84–0.99, P = 0.040). We therefore do not recommend quinolones as empirical therapy for community-acquired perforated appendicitis.

CD137 Expressed on Neutrophils Plays Dual Roles in Antibacterial Responses against Gram-Positive and Gram-Negative Bacterial Infections

ABSTRACT 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.

Adjuvant chemotherapy for elderly patients (aged 70 or older) with gastric cancer after a gastrectomy with D2 dissection: A single center experience in Korea.

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.

The presence of high level soluble herpes virus entry mediator in sera of gastric cancer patients

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.

The effectiveness of endoscopic submucosal resection with a ligation device for small rectal carcinoid tumors: focused on previously biopsied tumors.

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.

Silent invasion of Hem-O-Lok clip

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.

Mini‐breast reconstruction with an omental flap: a retrospective clinical study

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.

Ataxic gait following total gastrectomy for gastric cancer

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.