Who Can Perform Adjuvant Chemotherapy Treatment for Gastric Cancer? A Multicenter Retrospective Overview of the Current Status in Korea.

PURPOSE: To investigate the current status of adjuvant chemotherapy (AC) regimens in Korea and the difference in efficacy of AC administered by surgical and medical oncologists in patients with stage II or III gastric cancers. MATERIALS AND METHODS: We performed a retrospective observational study among 1,049 patients who underwent curative resection and received AC for stage II and III gastric cancers between February 2012 and December 2013 at 29 tertiary referral university hospitals in Korea. To minimize the influence of potential confounders on selection bias, propensity score matching (PSM) was used based on binary logistic regression analysis. The 3-year disease-free survival (DFS) rates were compared between patients who received AC administered by medical oncologists or surgical oncologists. RESULTS: Between February 2012 and December 2013 in Korea, the most commonly prescribed AC by medical oncologists was tegafur/gimeracil/oteracil (S-1, 47.72%), followed by capecitabine with oxaliplatin (XELOX, 16.33%). After performing PSM, surgical oncologists (82.74%) completed AC as planned more often than medical oncologists (75.9%), with statistical significance (P=0.036). No difference in the 3-year DFS rates of stage II (P=0.567) or stage III (P=0.545) gastric cancer was found between the medical and surgical oncologist groups. CONCLUSIONS: S-1 monotherapy and XELOX are a main stay of AC, regardless of whether the prescribing physician is a medical or surgical oncologist. The better compliance with AC by surgical oncologists is a valid reason to advocate that surgical oncologists perform the treatment of AC for stage II or III gastric cancers.

Effect of polylactic film (Surgi-Wrap) on preventing postoperative ileus after major hepato-pancreato-biliary surgery.

BACKGROUNDS/AIMS: Major hepato-pancreato-biliary (HPB) surgery is usually performed via an open method rather than a laparoscopic method. Postoperative ileus (POI) is a classic complication after open surgery. The purpose of this study was to determine whether polylactic film is useful in the prevention of POI. METHODS: A total of 179 patients who underwent major HPB surgery between 2005 and 2014, were retrospectively reviewed. A diagnosis of POI was made by a physical examination, laboratory, and radiological findings. Surgi-Wrap® polylactic film was preferentially used intraperitoneally by surgeons, just before wound closure. RESULTS: Major HPB surgery included pancreatoduodenectomy (n=48), distal or subtotal pancreatectomy (n=24), hepatectomy (n=67), other bile duct or gallbladder operations (n=35), and others (n=5). Although patients with polylactic film showed a significantly lower incidence of POI (n=3, 4.1% vs. n=14, 13.3%, p=0.041), they showed a significantly higher complication rate (n=20, 27.0% vs. n=19, 18.1%, p=0.004), particularly intra-abdominal fluid collection (n=7, 9.4% vs. n=2, 1.9%), and wound infections (n=6, 8.1% vs. n=3, 2.9%), than those who did not receive the film, respectively. CONCLUSIONS: Although the polylactic film prevented POI, more complications other than POI were observed. Well-designed randomized controlled trials, using this anti-adhesive product, are needed to evaluate its effect on POI after major HPB surgery.

Long-term outcomes of laparoscopy-assisted distal gastrectomy for early gastric cancer: result of a randomized controlled trial (COACT 0301).

BACKGROUND: The purpose of this study was to evaluate laparoscopy-assisted distal gastrectomy (LADG) compared to open distal gastrectomy (ODG) in the treatment of early gastric cancer with respect to survival, surgical outcomes, complications, and quality of life (QOL). METHODS: One hundred sixty-four patients with cT1N0M0 and cT1N1M0 distal gastric cancer were randomly assigned to either the LADG group or the ODG group. The primary end point was the 5-year disease-free survival (DFS) rate. Complications were classified using the accordion severity classification of postoperative complications scheme. QOL was measured using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-STO22 preoperatively and postoperatively during regular follow-up visits. This trial is registered at ClinicalTrials.gov (NCT00546468). RESULTS: The median (range) follow-up period was 74.3 (24.8-90.8) months. The LADG and ODG groups showed similar survival [5-year DFS rate: 98.8 % vs. 97.6 %, respectively (P = 0.514), 5-year overall survival (OS) rate: 97.6 vs. 96.3 %, respectively (P = 0.721)] or overall complication rate (29.3 vs. 42.7 %, respectively; P = 0.073). Mild complications were significantly less frequent in the LADG group than in the ODG group (23.2 vs. 41.5 %; P = 0.012). The rates of moderate, severe, and long-term complications (i.e., 31 days to 5 years after surgery) did not differ significantly between groups. No clinically meaningful differences were detected between the two groups in long-term QOL. CONCLUSION: LADG showed similar DFS and OS compared to ODG in treating early gastric cancer. Marginal benefits in mild complications were observed with LADG. LADG did not show advantages over ODG regarding other complications and long-term QOL.

Can serum interleukin-2 receptor alpha predict lymph node metastasis in early gastric cancer?

PURPOSE: Although local resection like endoscopic mucosal resection for early gastric cancer is accepted as a treatment option, one of the most important drawbacks of such an approach is the inability to predictlymph node metastasis. The aim of this study was to evaluate the serum soluble receptor alpha for interleukin-2 (IL-2Rα) level as a predictor of lymph node metastasis in the patients with early gastric cancer. METHODS: Assessment of pre-operative serum IL-2Rα levels was performed on 86 patients with early gastric cancer treated by gastrectomies combined with D2 lymph node resections and 20 healthy controls at Samsung Medical Center. Data on patient age and gender, tumor size, depth of invasion, histologic differentiation, and endoscopic findings were reviewed post-operatively. The submucosal lesions were divided into three layers (sm1, sm2, and sm3) in accordance with the depth of invasion. RESULTS: Lymph node metastasis was observed in 16 patients (18.6%). Statistically, the serum IL-2Rα level was an important predictive factor of lymph node metastasis in undifferentiated gastric cancer, and the cut-off point for the predictive value of serum IL-2Rα level was 200 U/mL. CONCLUSION: The serum IL-2Rα level might be a good predictor of lymph node metastasis in undifferentiated early gastric cancer.

The prognosis of gastric cardia cancer after R0 resection.

BACKGROUND: The aim of this study was to evaluate the prognosis of gastric cardia cancers in comparison with other gastric cancers. METHODS: The medical records of 251 patients with gastric cardia cancers and 6568 patients with other gastric cancers who underwent R0 resection were reviewed. Clinicopathologic characteristics and survival were analyzed. RESULTS: Gastric cardia cancer was associated with more advanced staging and less favorable clinicopathologic features at diagnosis compared with other gastric cancers. The overall 5-year survival rates were 79.7% and 84.6% in patients with cardia cancer and other cancers, respectively. There were no significant differences in survival curves between the groups at any stage. Lymph node metastasis was an independent prognostic factor for disease-free survival. The length of the proximal margin was not associated with locoregional tumor recurrence. CONCLUSIONS: Although patients with gastric cardia cancers are diagnosed at an advanced stage, the long-term survival rates are similar to those with other gastric cancers. If curative resection with negative resection margin can be achieved, pN category is the only prognostic factor for survival.

Expression levels of cyclin G2, but not cyclin E, correlate with gastric cancer progression.

PURPOSE: Cyclin G2 and cyclin E are important cell-cycle regulators in various cancer tissues. However, little is known about cyclin G2 expression in human gastric cancer tissues, and the role of cyclin E is quite controversial. This study evaluated their clinical significance in gastric cancer tissues. MATERIALS AND METHODS: Immunohistochemical staining using the tissue array method was performed on 166 human gastric carcinomas. The clinicopathological features and prognostic significance were analyzed. RESULTS: Cyclin G2 and cyclin E expressions were positive in 110 (66.3%) and 77 (46.4%) human gastric cancer tissues, respectively. The incidence of cyclin G2 positivity was lower in females and in cancers with the undifferentiated type of histology. Moreover, cyclin G2 expression was inversely correlated with the more advanced stages (P < 0.05), the presence of lymph-node metastasis (P < 0.05), and the presence of perineural invasion (P < 0.05). However, no significant correlation was observed between the expression of cyclin E and all of the clinicopathological factors examined. Cyclin G2 expression was associated with a better overall survival (OS; 5-y OS, 50.6% for cyclin G2-positive versus 35.0% for cyclin G2-negative; P < 0.05). However, multivariate analysis revealed lymph-node metastasis, distant metastasis, and lymphatic invasion to be independent prognostic factors but not cyclin G2 expression. CONCLUSION: Our study could not demonstrate any significant relationship between cyclin E expression and the clinicopathological variables. However, cyclin G2 appears to be a negative cell-cycle regulator in gastric cancer, and its expression seems to be inversely related to gastric cancer progression.

Improved quality of life outcomes after laparoscopy-assisted distal gastrectomy for early gastric cancer: results of a prospective randomized clinical trial.

OBJECTIVE: The purpose of this study was to evaluate the quality of life (QOL) after laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG) in patients with early gastric cancer. SUMMARY BACKGROUND DATA: LADG has been beneficial in terms of pain, recovery, and morbidity when compared with open surgery with equal oncologic outcome. There has been no clinical study on QOL. METHODS: From July 2003 to November 2005, 164 patients with newly diagnosed cT1N0M0 and cT1N1M0 distal gastric cancer were randomly assigned either to LADG or ODG. All patients were asked to complete the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-STO22 questionnaires preoperatively and postoperatively on regular follow-up visits. RESULTS: Statistically significant differences were observed with a more favorable outcome noted in the LADG group with respect to intraoperative blood loss (P < 0.001), total amount of analgesics used (P = 0.019), the size of the wound (P < 0.0001), postoperative hospital stay (P < 0.0001), and QOL parameters of global health (P < 0.0001). Most of the scales on patient functioning including physical (P < 0.0005), role (P = 0.0011), emotional (P < 0.0001), social (P < 0.0001), and symptom scales such as fatigue (P < 0.0001), pain (P < 0.0001), appetite loss (P = 0.031), sleep disturbance (P = 0.003), dysphasia (P = 0.0024), gastro-esophageal reflux (P = 0.0127), dietary restriction (P = 0.0004), anxiety (P = 0.0036), dry mouth (P = 0.0007), and body image (P < 0.0001) were also significantly better in the LADG group compared with the ODG group. CONCLUSIONS: Comparison of LADG to ODG in patients with early gastric cancer resulted in improved QOL outcomes in the patients followed for up to 3 months in the LADG group.

Inhibition of lipopolysaccharide-induced nitric oxide synthesis by nicotine through S6K1-p42/44 MAPK pathway and STAT3 (Ser 727) phosphorylation in Raw 264.7 cells.

Lipopolysaccharide (LPS) has been known to produce inflammatory modulators such as tumor necrosis factor alpha (TNF-alpha) or nitric oxide (NO). In this study, we examined the effects of nicotine on LPS enhanced NO synthesis and inducible nitric oxide synthase (iNOS) expression in macrophages. LPS-induced NO synthesis and iNOS expression were significantly decreased by nicotine. To investigate the signaling mechanism of nicotine induced suppression of NO synthesis and iNOS expression induced by LPS, we focused on the possible roles of p42/44 MAPK, S6K1, and signal transducers and activators of transcription 3 (STAT3) signaling. LPS is known to activate p42/44 MAPK and S6K1, which in turn activates STAT3 to induce inflammatory regulators. Pretreatment of cells with nicotine blocked LPS-induced p42/44 MAPK and S6K1 as well as iNOS promoter activity. Furthermore, we found that LPS-induced phosphorylation of STAT3 at serine 727 is mediated by S6K1-p42/44 MAPK pathway, and this STAT3 phosphorylation was also blocked by nicotine. We also found that downregulation of STAT3 using STAT3 siRNA resulted in suppression of the NO synthesis and iNOS expression. Taken together, our results suggest that nicotine inhibits LPS-induced NO synthesis through suppression of S6K1-p42/44 MAPK pathway and phosphorylation of STAT3 in Raw 264.7 cells.

Predictive factors for lymph node metastasis in early gastric cancer with submucosal invasion: analysis of a single institutional experience.

OBJECTIVE: An accurate assessment of a potential lymph node metastasis is an important issue for the appropriate treatment of early gastric cancer. Minimizing the amount of invasive procedures used in cancer treatment is critical for improving the patient's quality of life. Therefore, this study analyzed the predictive risk factors for a lymph node metastasis in early gastric cancer with a submucosal invasion. METHODS: The data from 1043 patients surgically treated for early gastric cancer with submucosal invasion between 2002 and 2005 were reviewed retrospectively. The patients were divided into 3 layers according to their depth: SM1, SM2, and SM3. The clinicopathological variables predicting a lymph node metastasis were evaluated. RESULTS: A lymph node metastasis was observed in 19.4% of patients. The tumor size, histologic type, Lauren classification, tumor depth, and perineural invasion showed a positive correlation with the rate of lymph node metastasis and N category by univariate analysis. Multivariate analyses revealed the tumor size (>or=2 cm) and lymphatic involvement to be significantly and independently related to lymph node metastasis. The presence of lymphatic involvement was the strongest predictive factor for a lymph node metastasis, being observed in 43.8% of cases in which a lymph node metastasis had been revealed. No lymph node metastasis was observed in the 12 cases with no lymphatic involvement, SM1 invasion, and tumor size <1 cm. CONCLUSIONS: Lymphatic involvement and tumor size are independent risk factors for a lymph node metastasis in early gastric cancer with submucosal invasion. Minimal invasive treatment, such as endoscopic mucosal resection, may be possible in highly selective submucosal cancers with no lymphatic involvement, SM1 invasion, and tumor size <1 cm.