Short-term outcomes of a multicentre randomized clinical trial comparing laparoscopic pylorus-preserving gastrectomy with laparoscopic distal gastrectomy for gastric cancer (the KLASS-04 trial).

BACKGROUND: There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer. METHODS: The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days. RESULTS: Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups. CONCLUSION: Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).

Prevalence and risk factors of chronic rhinosinusitis in South Korea according to diagnostic criteria.

BACKGROUND: We aimed to compare the prevalence and risk factors of chronic rhinosinusitis (CRS) using two different diagnostic criteria with the same statistical data from the Korean National Health and Nutrition Examination Survey in 2009. METHODS: Symptom-based CRS was defined as CRS diagnosed by questionnaires related to nasal symptoms. Endoscopy-based CRS was defined based on endoscopic findings and nasal symptoms of symptom-based CRS. RESULTS: The overall prevalence of CRS based on the different diagnostic criteria was as follows: symptom-based CRS was 10.78% (797 of 7,394) and endoscopy-based CRS was 1.20% (88 of 7,343). Comparing symptom-based CRS to endoscopy-based CRS showed slight agreement (kappa = 0.183 (0.150-0.216, 95% confidence interval)). Allergic rhinitis was identified as a common risk factor for CRS based on the two diagnostic criteria. CONCLUSIONS: The prevalence and risk factors of CRS were quite different from each other according to the different criteria, even in the same population. Therefore, it would be important to consider what specific diagnostic criteria have been adopted in the studies comparing the prevalence of CRS.

Stomach hanging technique using gauze during laparoscopic gastrectomy.

INTRODUCTION: Lifting the stomach using laparoscopic instruments during laparoscopic gastrectomy is difficult and increases the risk of crushing the tumor. In this study, we present a stomach hanging technique using gauze pieces that reduces the risk to the tumor. MATERIALS AND SURGICAL TECHNIQUE: After a partial omentectomy and the opening of the lesser sac, the antrum was wrapped with a 15-20-cm gauze piece. Next, a straight needle with 2-0 monofilament suture material pierced the abdominal cavity through the right subcostal area on the mid-clavicular line, and the gauze was then sutured twice in a figure of eight manner. The needle was removed percutaneously through the right middle quadrant of the abdomen. Another suture was applied to wrap the left side of the stomach. The stomach was easily lifted and positioned by pulling the four suture strings in different directions. After the suture materials were fastened to the abdominal wall using hemostat forceps, the surgical field was sufficiently exposed, facilitating lymph node dissection on the superior surface of the pancreas. This method freed the assistant from holding the stomach and enabled this individual to assist the operation in other ways. DISCUSSION: This stomach lifting technique using gauze is a good option for exposing the surgical field, enables the assistant to perform other tasks, and reduces the risk of crushing the tumor during laparoscopic gastrectomy.

Reliability and validity of measuring version of the acetabular component.

A variety of radiological methods of measuring version of the acetabular component after total hip replacement (THR) have been described. The aim of this study was to evaluate the reliability and validity of six methods (those of Lewinnek; Widmer; Hassan et al; Ackland, Bourne and Uhthoff; Liaw et al; and Woo and Morrey) that are currently in use. In 36 consecutive patients who underwent THR, version of the acetabular component was measured by three independent examiners on plain radiographs using these six methods and compared with measurements using CT scans. The intra- and interobserver reliabilities of each measurement were estimated. All measurements on both radiographs and CT scans had excellent intra- and interobserver reliability and the results from each of the six methods correlated well with the CT measurements. However, measurements made using the methods of Widmer and of Ackland, Bourne and Uhthoff were significantly different from the CT measurements (both p < 0.001), whereas measurements made using the remaining four methods were similar to the CT measurements. With regard to reliability and convergent validity, we recommend the use of the methods described by Lewinnek, Hassan et al, Liaw et al and Woo and Morrey for measurement of version of the acetabular component.

The effects of mesenchymal stem cells injected via different routes on modified IL-12-mediated antitumor activity.

Owing to its tumor tropism and prolonged transgene expression, mesenchymal stem cell (MSC) has been considered as an ideal delivery vehicle for cancer gene therapies or therapeutic vaccines. In this study, we demonstrated that intratumoral (i.t.) injection of MSCs expressing modified interleukin-12 (MSCs/IL-12M) exhibited stronger tumor-specific T-cell responses and antitumor effects as well as more sustained expressions of IL-12 and interferon (IFN)-γ in both sera and tumor sites than did IL-12M-expressing adenovirus (rAd/IL-12M) in mice bearing both solid and metastatic tumors. Subcutaneous (s.c.) injection of MSCs/IL-12M at contralateral site of tumor exhibited similar levels of serum IL-12 and IFN-γ as i.t. injection, but much weaker antitumor effects in both B16F10 melanoma and TC-1 cervical cancer models than i.t. injection. Although intravenous (i.v.) injection elicited earlier peak serum levels of cytokines, it induced weaker tumor-specific T-cell responses and antitumor effects than i.t. injection, indicating that serum cytokine levels are not surrogate indicators of antitumor effects. Taken together, these results indicated that MSC is more efficient than adenovirus as a cytokine gene delivery vehicle and that i.t. injection of MSCs/IL-12M is the best approach to induce strong tumor-specific T-cell responses that correlate with anti-metastatic effects as well as inhibition of solid tumor growth, although MSCs themselves have an ability to migrate into the tumor site. In addition, MSCs/IL-12M embedded in Matrigel (MSCs/IL-12M/Matrigel) exhibited significant antitumor effects even in immunodeficient mice such as SCID and BNX mice lacking T, B and natural killer (NK) cells, but not in IFN-γ knockout mice. Our findings provide an optimal approach for designing an efficient clinical protocol of MSC-based cytokine gene therapy to induce strong tumor-specific T-cell responses and therapeutic anticancer efficacy.

Characterization of chromosomal aberrations in human gastric carcinoma cell lines using chromosome painting.

Using chromosome painting, a study of chromosomal abnormalities was performed in six gastric carcinoma cell lines (SNU-484, 601, 620, 638, 668, 719) from Korean patients. Each carcinoma cell line had unique modal karyotypic characteristics and showed a variable number of numerical and structural clonal cytogenetic aberrations. SNU-484, SNU-620, and SNU-668 had near-triploidy; SNU-601, SNU-638, and SNU-719 had near-diploidy. The origins of the marker chromosomes of these cell lines were identified by fluorescence in situ hybridization with constructed painting probes. In all of six cell lines, rearrangement of chromosome 17 resulting in partial deletion of 17p (and/or partial duplication of 17q) was found. The most frequent marker was a partial gain of chromosome 7 with the breakpoints on 7q22 and 7q31. The nonrandom rearrangements of chromosomes were also determined on 1q32, 5q11-q22, 8q, 14q22, 14q34, and 15q15; suggesting that they may be the candidate regions for the isolation of the genes related to gastric cancer.

Enhancement of immunoglobulin G2a and cytotoxic T-lymphocyte responses by a booster immunization with recombinant hepatitis C virus E2 protein in E2 DNA-primed mice.

The induction of strong cytotoxic T-lymphocyte (CTL) and humoral responses appear to be essential for the elimination of persistently infecting viruses, such as hepatitis C virus (HCV). Here, we tested several vaccine regimens and demonstrate that a combined vaccine regimen, consisting of HCV E2 DNA priming and boosting with recombinant E2 protein, induces the strongest immune responses to HCV E2 protein. This combined vaccine regimen augments E2-specific immunoglobulin G2a (IgG2a) and CD8(+) CTL responses to a greater extent than immunizations with recombinant E2 protein and E2 DNA alone, respectively. In addition, the data showed that a protein boost following one DNA priming was also effective, but much less so than those following two DNA primings. These data indicate that sufficient DNA priming is essential for the enhancement of DNA encoded antigen-specific immunity by a booster immunization with recombinant E2 protein. Furthermore, the enhanced CD8(+) CTL and IgG2a responses induced by our combined vaccine regimens are closely associated with the protection of BALB/c mice from challenge with modified CT26 tumor cells expressing HCV E2 protein. Together, our results provide important implications for vaccine development for many pathogens, including HCV, which require strong antibody and CTL responses.

DNA inoculations with HIV-1 recombinant genomes that express cytokine genes enhance HIV-1 specific immune responses.

Vaccination with HIV-1 DNA sequences induce both humoral and cellular immune responses in experimental animals. However, these responses are relatively weak and are often only transient in their nature. In order to enhance the level of HIV-1 specific immunity, we have engineered HIV-1 DNA constructs which contained various cytokine genes such as interleukin-2 (IL-2), granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) gene. These constructs have deleted the tat and nmf genes of HIV-1 to eliminate their immunosuppressive effects. Immunizations with these recombinant constructs elicited moderate proliferative T cell responses but poor antibody responses in rats. However, inoculations of HIV-1 DNA that contained the GM-CSF or the IL-2 gene significantly enhanced humoral and proliferative T cell responses, respectively. Thus, recombinant HIV-1 genomes such as those described here may increase the efficacy of DNA vaccination.

Protective immunity against heterologous challenge with encephalomyocarditis virus by VP1 DNA vaccination: effect of coinjection with a granulocyte-macrophage colony stimulating factor gene.

For DNA vaccination studies, recombinant VP1 protein of encephalomyocarditis virus (EMCV) was produced from Escherichia coli, and eukaryotic VP1 expression vector, pCT-Gs-VP1, was generated and used as a DNA vaccine. Mice were immunized intramuscularly (i.m.) with pCT-Gs-VP1 in the presence or absence of plasmid DNA expressing granulocyte-macrophage colony stimulating factor (GM-CSF), and were subsequently analyzed for their anti-VP1 immune responses with recombinant VP1 in ELISA. Immunization of mice with pCT-Gs-VP1 resulted in VP1-specific immune response and 43% protection from subsequent lethal heterologous challenge of EMCV. Coinjection of mice with pCT-Gs-VP1 and plasmid DNA encoding GM-CSF was shown to increase the seroconversion rate of the immunized mice with a single DNA injection, and enhanced to a higher degree VP1-specific immunity, which appeared to result in better protection (about 80%) from lethal virus challenge. Thus, our results provide evidence for the potential use of GM-CSF to induce better immune response and resistance against viral infection in DNA vaccination.

Comparison of various expression plasmids for the induction of immune response by DNA immunization.

Intramuscular injection of plasmid DNA is an efficient method to introduce a foreign gene into a live animal. We investigated several factors affecting the gene transfer efficiency and the following immune response by intramuscular injection of plasmid DNA. When the strength of several highly efficient viral promoters was compared in muscle by using the chloramphenicol acetyltransferase (CAT) gene as an indicator, cytomegalovirus (CMV) immediate early promoter was found to be stronger than any other viral promoters including Rous sarcoma virus (RSV), murine leukemia virus (SL3-3) and simian virus 40 (SV40) early promoters. Inclusion of adenovirus tripartite leader (TPL) sequences and a synthetic intron in the 5' untranslated region of mRNA moderately stimulated the CAT expression. On the other hand, the expression of encephalomyocarditis virus (EMCV) VP1 gene was greatly enhanced by the TPL sequences and an intron. The level of humoral immune response by intramuscular injection of various VP1 expression plasmids was compared. The seroconversion rate was highly dependent on the strength of the expression vector. However, the ratio of IgG1 and IgG2a immune response was not significantly variable depending on the strength of the expression vector. Also, the efficiency of the sindbis virus-based DNA vector was examined for the gene expression and immune response. Although a high level of CAT expression was obtained in muscle by using this system, VP1 was not produced as much as the conventional expression vectors. Furthermore, little humoral immune response was elicited by intramuscular injection of VP1-expressing sindbis vector, suggesting that this system was not superior to the conventional vector for DNA immunization.