PWWP2B promotes DNA end resection and homologous recombination.

Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development.

RNF43 and PWWP2B inhibit cancer cell proliferation and are predictive or prognostic biomarker for FDA-approved drugs in patients with advanced gastric cancer.

Background: Abnormal regulation of genes has been closely related to gastric cancer. The characterization of gastric cancer has necessitated the development of new therapeutics as well as the identification of prognostic markers to predict the response to novel drugs. In our study, we used RNA sequencing analyses to show that on gastric cancer tissues to identification of gastric cancer prognostic markers. We specifically chose to study RNF43 because it inhibits gastric cancer-related Wnt/ß-catenin signaling by interacting with Wnt receptors. PWWP2B was chosen because it is a gene which is downregulated in gastric cancer. Methods: Utilizing RNA sequencing analysis, we evaluated the mRNA expression profile in gastric cancer patients. Also, we used HAP1 cells which is a human near-haploid cell line derived from the male chronic myelogenous leukemia cell line KBM-7. These cell line has one copy of each gene, ensuring the edited allele will not be masked by additional alleles. We investigated the screening of 1,449 FDA-approved drugs in HAP1, HAP1 RNF43 KO and HAP1 PWWP2B KO cells. RNA sequencing data reveals that RNF43 and PWWP2B expression were down-regulated in recurrence gastric cancer patients. Next, we investigated the anti-cancer effects of selected drugs in RNF43 and PWWP2B down-regulated MKN45 gastric cancer cells and xenograft model. Results: Among these FDA-approved drugs, three drugs (docetaxel trihydrate, pelitinib and uprosertib) showed strong inhibitory effects in RNF43 KO cells and PWWP2B KO cells. In MKN45 xenograft model, tumor volumes were significantly reduced in the docetaxel trihydrate, uprosertib or pelitinib-treated group. Our data demonstrated that RNF43 and PWWP2B are a biomarker that predict recurrence of gastric cancer. Conclusions: Our findings suggest that docetaxel trihydrate, uprosertib and pelitinib could be used as novel therapeutic agents for the prevention and treatment of gastric cancer with a decrease in RNF43 and PWWP2B expression.

Phase II study of oxaliplatin, irinotecan and S-1 therapy in patients with advanced gastric cancer: the Korean Cancer Study Group ST14-11.

BACKGROUND: Doublet chemotherapy of platinum and 5-fluorouracil is a standard first-line treatment for patients with unresectable gastric cancer. Although the addition of taxane or irinotecan to this regimen has yielded promising efficacy, its use has been limited due to severe toxicities. To overcome this limitation, we evaluated the efficacy and safety of the combination of irinotecan, oxaliplatin, and S-1 (OIS) for the treatment of advanced gastric cancer. METHODS: Chemotherapy-naïve patients with pathologically proven advanced gastric adenocarcinoma were assessed for eligibility. Irinotecan (135 mg/m2) and oxaliplatin (65 mg/m2) were administered intravenously on day 1, and S-1 (80 mg/m2/day) was administered orally on days 1-7 of every 2-week cycle. RESULTS: Forty-four patients (median age 57 years) were enrolled and all but one patient had a good performance status (ECOG 0 or 1). A total of 529 cycles were administered, with a median of 9.5 (range 1-31) cycles per patient. The overall response rate was 61.4% (95% confidence interval [CI] 46.6-74.3). The median progression-free survival and overall survival were 10.8 months (95% CI 7.6-14.0) and 15.4 months (95% CI 12.6-18.2), respectively. Major toxicities included grade 3/4 neutropenia (38.6%), febrile neutropenia (13.6%), abdominal pain (9.1%), and diarrhea (9.1%). CONCLUSION: These data suggest that the OIS regimen is effective and relatively well tolerated in patients with advanced gastric cancer. Given that all the patients treated, but one, had a good performance status, these results must be confirmed in a patient population more representative of regular clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02527785.

Programmed death ligand-1 and MET co-expression is a poor prognostic factor in gastric cancers after resection.

Programmed death-ligand 1 (PD-L1) plays an essential protein for immune evasion, contributing to tumor development and progression. Recent studies have reported MET as an upregulator for PD-L1 overexpression through an oncogenic pathway. However, an association between PD-L1 expression with MET has not been reported in gastric cancer.The prognostic significance of PD-L1 and its association with Epstein-Barr virus (EBV), microsatellite instability (MSI), and mucin phenotype remain controversial. We performed in situ hybridization for EBV-encoded RNA and immunohistochemistry in tissue microarrays for 394 gastric cancers. A multiplex polymerase chain reaction with five quasimonomorphic markers was performed for MSI. PD-L1 expression was observed in 123 cases (31.2%), and clinicopathological features such as MET overexpression, high pT stage, and a lack of lymphatic invasion represent significant risk factors associated with PD-L1 overexpression in gastric cancers. No associations of EBV, MSI, or mucin phenotype with PD-L1 expression were statistically significant. PD-L1 expression was a strong indicator for worse overall survival (OS) but borderline significant in disease-free survival (DFS). A combined analysis of PD-L1 and MET expression indicated that the PD-L1+/MET+ subgroup showed the worst prognosis when compared to the PD-L1-/MET- subgroup, which had the best clinical outcome. Furthermore, PD-L1 overexpression exhibited poor prognosis in terms of both OS and DFS in EBV-negative, microsatellite stable, and intestinal mucin phenotype tumors. In conclusion, this is the first study to evaluate the overexpression of MET as a risk factor for PD-L1 positivity in gastric cancer tissue as well as the reliability and prognostic relevance of PD-L1/MET co-expression after surgery.

Does the discrepancy in histologic differentiation between a forceps biopsy and an endoscopic specimen necessitate additional surgery in early gastric cancer?

AIM: To investigate the clinicopathological variables in early gastric cancer (EGC) patients in relation to differentiation discrepancy. METHODS: The data of 265 specimens from 240 patients with EGC, who had undergone radical operation at Hallym University Sacred Heart Hospital from 2010 to 2015, were retrospectively analyzed. We evaluated clinical, endoscopic, and histopathological data according to histological discrepancy. RESULTS: Clinically significant discrepancy rate showed the difference in differentiated type (well and moderately differentiated) and undifferentiated type (poorly differentiated and signet ring cell) between endoscopic biopsies and postoperative specimens was 9.4% (25/265). There were no differences in tumor location, size, gross pattern, and number of biopsies. Specimens having histological discrepancy showed more submucosal invasion (72.0% vs 49.6%, P = 0.033) and lymph node involvement (24.0% vs 7.9%, P = 0.009) than specimens having non-discrepancy. The rate of a positive epidermal growth factor receptor status was higher in specimens having discrepancy than in specimens having non-discrepancy (81.0% vs 55.4%, P = 0.035). CONCLUSION: The discordance of histologic differentiation is associated with higher submucosal invasion and lymph node metastases in EGC. Patients have histological discrepancy may require additional surgical treatments.

Is it beneficial to perform surgical resection in elderly patients more than 80 years old with advanced gastric cancer?

OBJECTIVES: With the aging population, the number of elderly patients diagnosed with gastric cancer is increasing. However, determining treatment strategies for elderly patients with gastric cancer is controversial. The aim of this study is to evaluate the usefulness of surgical treatment on elderly patients aged ≥80 years with advanced gastric cancer. METHODS: A total of 147 elderly patients who were diagnosed with advanced gastric cancer from August 2001 to December 2015 were retrospectively analyzed. We compared the clinicopathological features and prognoses of 94 elderly patients (80-85 years) and 53 extreme-elderly patients (≥86 years) according to treatment modalities. RESULTS: In the elderly group, the 3-year overall survival (OS) rates of the surgical resection group and supportive care group were 42.1% and 4.0%, respectively (p < .001). In the extreme-elderly group, the 3-year OS rates of the surgical resection group and supportive care group were 36.4% and 8.0%, respectively (p = .028). The post-operative mortality rate of the elderly group and extreme-elderly group was 5.6% and 9.1%, respectively. In the analysis of risk factors associated with survival, surgical resection was a significantly good prognostic factor in the elderly group (hazard ratio [HR] = 0.277; p = .003) compared with supportive care. In the extreme-elderly group, surgical resection was associated with good prognosis but did not reach statistical significance (HR = 0.491; p = .099). CONCLUSIONS: These results suggest that elderly patients aged 80-85 years with advanced gastric cancer could expect a better prognosis with surgical resection. However, extreme-elderly patients aged ≥86 years should consider the risks and benefits of surgical treatment.

A dose-finding study for oxaliplatin, irinotecan, and S-1 (OIS) in patients with metastatic or recurrent gastrointestinal cancer.

PURPOSES: To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined oxaliplatin, irinotecan, and S-1 chemotherapy for metastatic or recurrent gastrointestinal (GI) cancer. METHODS: Oxaliplatin and irinotecan were administered intravenously on day 1, and S-1 was administered orally on days 1-7, every 2 weeks. This phase I study used the following dose levels for oxaliplatin/irinotecan/S-1: level 1, 85/120/60 mg/m2; level 2, 85/120/80 mg/m2; level 3, 85/120/100 mg/m2; level 4, 85/150/100 mg/m2; and level 5, 85/180/100 mg/m2. Treatment was repeated for a maximum of 12 cycles, until disease progression, or until unacceptable toxicity. RESULTS: Twenty-four patients were enrolled between October 2012 and February 2014 (median age 59 years). During the first cycle, one of the six patients in levels 1, 3, and 4 developed a dose-limiting toxicity (grade 3 febrile neutropenia), and none of the three patients in level 5 developed a dose-limiting toxicity. As the planned maximum dose did not reach the MTD, the level 5 dose was defined as the RD. Twenty-one patients were evaluated for response, which included 2 cases of complete response and 8 cases of partial response, with an overall response rate of 47.6 %. CONCLUSIONS: The combination of oxaliplatin, irinotecan, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced GI cancer. The RD was 85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan, and 100 mg/m2 of S-1 every 2 weeks.

A phase II study of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy followed by surgery and adjuvant S-1 chemotherapy in potentially resectable gastric or gastroesophageal junction adenocarcinoma.

PURPOSE: Adjuvant chemotherapy trial of TS-1 for gastric cancer study demonstrated that postoperative S-1 chemotherapy for 1 year improved overall survival of locally advanced gastric cancer (LAGC) patients. The goals of this study were to evaluate the feasibility and efficacy of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy followed by surgery and adjuvant S-1 chemotherapy. METHODS: In this single-center, open-label, phase II study, patients with potentially resectable adenocarcinoma of the stomach or gastroesophageal junction were eligible. For neoadjuvant chemotherapy, docetaxel 50 mg/m(2) on day (D) 1, oxaliplatin 100 mg/m(2) on D1, and S-1 40 mg/m(2) bid orally on D1-14 were administrated every 3 weeks for three cycles. After DOS chemotherapy, gastrectomy was performed, and then, adjuvant S-1 40 mg/m(2) bid was given on D1-28 every 6 weeks for 1 year. The primary endpoints were the proportion of patients who did not experience grade 3 or 4 toxicities (except grade 3 neutropenia) and R0 resection rates. RESULTS: A total of 41 patients were enrolled. All patients completed three planned cycles of neoadjuvant chemotherapy without disease progression. Eighteen patients (43.9 %) did not experience any grade 3-4 toxicity (except grade 3 neutropenia) during the neoadjuvant chemotherapy. All patients underwent surgery, and R0 resection was achieved in 40 patients (97.6 %). CONCLUSION: Neoadjuvant DOS chemotherapy could be performed safely with a high R0 resection rate in LAGC patients. A phase III trial is currently underway.

Early experiences of minimally invasive surgery to treat gastroesophageal reflux disease.

PURPOSE: There are fewer patients with gastroesophageal reflux disease (GERD) in Korea compared with Western countries. The incidence of GERD has increased in recent years however, concerning many physicians. Here, we report our early experiences of using a recently introduced method of laparoscopic antireflux surgery for the treatment of GERD in Korean patients. METHODS: Fifteen patients with GERD were treated using antireflux surgery between May 2009 and February 2012 at the University of Ulsan College of Medicine and Asan Medical Center. Laparoscopic Nissen fundoplication with 360° wrapping was performed on all patients. RESULTS: Eleven male and four female patients were evaluated and treated with an average age of 58.1 ± 14.1 years. The average surgical time was 118.9 ± 45.1 minutes, and no complications presented during surgery. After surgery, the reflux symptoms of each patient were resolved; only two patients developed transient dysphagia, which resolved within one month. One patient developed a 6-cm hiatal hernia that had to be repaired and reinforced using mesh. CONCLUSION: The use of laparoscopic surgery for the treatment of GERD is safe and feasible. It is also an efficacious method for controlling the symptoms of GERD in Korean patients. However, the use of this surgery still needs to be standardized (e.g., type of surgery, bougienage size, wrap length) and the long-term outcomes need to be evaluated.

Quality of life, immunomodulation and safety of adjuvant mistletoe treatment in patients with gastric carcinoma - a randomized, controlled pilot study.

BACKGROUND: Mistletoe (Viscum album L.) extracts are widely used in complementary cancer therapy. Aim of this study was to evaluate safety and efficacy of a standardized mistletoe extract (abnobaVISCUM(®) Quercus, aVQ) in patients with gastric cancer. PATIENTS AND METHODS: 32 operated gastric cancer patients (stage Ib or II) who were waiting for oral chemotherapy with the 5-FU prodrug doxifluridine were randomized 1:1 to receive additional therapy with aVQ or no additional therapy. aVQ was injected subcutaneously three times per week from postoperative day 7 to week 24 in increasing doses. EORTC QLQ-C30 and -STO22 Quality of Life questionnaire, differential blood count, liver function tests, various cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)-2), CD 16(+)/CD56(+) and CD 19(+) lymphocytes were analyzed at baseline and 8, 16 and 24 weeks later. RESULTS: Global health status (p <0.01), leukocyte- and eosinophil counts (p ≤0.01) increased significantly in the treatment group compared to the control group. Diarrhea was less frequently reported (7% vs. 50%, p=0.014) in the intervention group. There was no significant treatment effect on levels of TNF-alpha, IL-2, CD16(+)/CD56(+) and CD 19(+) lymphocytes and liver function tests measured by ANOVA. CONCLUSION: Additional treatment with aVQ is safe and was associated with improved QoL of gastric cancer patients. ClinicalTrials.Gov Registration number NCT01401075.

Modified techniques and early outcomes of totally laparoscopic total gastrectomy with side-to-side esophagojejunostomy.

BACKGROUND: Construction of an esophagojejunostomy is a major concern in totally laparoscopic total gastrectomy (TLTG). Use of a circular stapler can be technically challenging in laparoscopic procedures. We aimed to introduce our modified techniques and to assess the early outcomes following TLTG with side-to-side esophagojejunostomy using a linear stapler in patients with gastric cancer. SUBJECTS AND METHODS: From December 2010 to June 2011, 27 patients who underwent TLTG for gastric cancer were retrospectively reviewed. Their clinicopathologic characteristics, surgical time, hospital stay, morbidity, and mortality were analyzed. RESULTS: The mean age of patients was 59.1 years, and the average body mass index was 24.6 kg/m(2). The mean operating time was 126.2 minutes, and the hospital stay averaged 8.1 days. No conversion to open laparotomy was required. There were 2 luminal bleeding cases and 1 intra-abdominal bleeding case, but all were successfully managed with conservative treatment only. No patient experienced reoperation, anastomosis leakage, stricture, duodenal stump leakage, or wound problems. CONCLUSIONS: Our TLTG with side-to-side esophagojejunostomy method can be a feasible and safe option for patients with gastric cancer.

Multiple synchronous early gastric cancers: high-risk group and proper management.

BACKGROUND: Multiple early gastric cancers (MEGCs) may be easily missed on preoperative gastroscopy because the lesions are predominantly small and flat. This may increase the risks of gastric remnant lesions and recurrence. We aimed to define high-risk group of MEGC and suggest proper management of missed lesion after partial gastrectomy. METHODS: A total of 117 patients with MEGCs and 2182 with solitary EGC who underwent gastrectomy between 2008 and 2010 were retrospectively analyzed to determine their clinicopathologic characteristics. We also assessed their family history, the presence of Helicobacter pylori infection, and of precancerous lesions; and the results of microsatellite instability and immunohistochemical staining of the primary (largest) lesion for p53, human epidermal growth factor receptor [HER1], and HER2 were also reviewed. RESULTS: MEGCs occurred more frequently in elderly males and in patients with adenoma, atrophic gastritis, or a family history of gastric cancer. These patients had more favorable pathologic findings, including less deep invasion, better differentiation, more intestinal type, and less frequent lymphovascular/perineural invasion than patients with solitary EGCs. The mean size of MEGCs was smaller (2.44 cm vs 3.36 cm) but there was no difference in the number of metastatic lymph nodes. Most accessory lesions were confined to the mucosal layer, with their average diameter was 1.82 cm. CONCLUSIONS: A careful preoperative gastroscopy should be performed in patients at high risk of MEGCs and more cautious postoperative endoscopic surveillance of the remnant stomach is required. For missed foci on remnant stomach, endoscopic resection can be a good option if it meets the criteria.

Safety and feasibility of adjuvant chemotherapy with S-1 for Korean patients with curatively resected advanced gastric cancer.

BACKGROUND: Adjuvant chemotherapy with S-1 was proven to be effective in Japanese patients with advanced gastric cancer curatively resected with D2 lymph node dissection. MATERIALS AND METHODS: We retrospectively evaluated the medical records of 305 patients with stage II, III or IV (M0) gastric cancer who had received adjuvant S-1 chemotherapy following curative gastrectomy with D2 lymph node dissection between October 2007 and December 2009. Adjuvant S-1 was administered at a dose of 40 mg/m(2) twice daily for 4 weeks followed by 2 weeks of rest, every 6 weeks for eight cycles. RESULTS: Of the 305 patients, 248 (81.3 %) and 198 (64.9 %) completed four and eight cycles of adjuvant chemotherapy, respectively. The most common reasons for discontinuing treatment prior to the planned eight cycles were adverse events (n = 47, 15.4 %) and tumor recurrence (n = 28, 9.2 %). Sixty-five (21.3 %) patients required dose reduction due to adverse events. The most common grade 3/4 toxicities were neutropenia (n = 39, 12.8 %), diarrhea (n = 15, 4.9 %). Multivariate analysis showed that total gastrectomy [odds ratio (OR) 2.44; 95 % confidence interval (CI) 1.29-4.62, p = 0.006] was an independent risk factor for grade 3/4 hematologic toxicities, and age > 65 years (OR 2.60; 95 % CI 1.34-5.07, p = 0.005) was an independent risk factor for grade 3 non-hematologic toxicities. CONCLUSIONS: Adjuvant chemotherapy with S-1 for 1 year is safe and feasible in Korean patients. Age > 65 years and total gastrectomy are independent risk factors for severe adverse events caused by adjuvant S-1 chemotherapy.

A comparison between single-incision and conventional laparoscopic cholecystectomy.

BACKGROUND: Single-incision laparoscopic surgery is becoming a more widely accepted surgical approach. However, the feasibility and safety of single-incision laparoscopic cholecystectomy (SILC) are yet to be established. The present study compared outcomes following the use of SILC or conventional laparoscopic cholecystectomy (CLC) on patients with gallbladder disease. SUBJECTS AND METHODS: The study involved 190 symptomatic gallbladder disease patients treated between March 2009 and February 2011. Ninety-six patients underwent SILC, and 94 patients underwent CLC. Clinical and surgical outcomes were compared. RESULTS: The SILC and CLC groups were similar in terms of age, gender ratio, body mass index, and diagnoses. The two groups were also found to be similar in terms of postoperative clinical course and complications. The SILC group had a longer operation time, less postoperative pain, and a shorter hospital stay than the CLC group (P<.05 for all variables). CONCLUSIONS: SILC using the OCTO port system (Darim Corp., Korea) was as safe and feasible as CLC. Additionally, SILC is less invasive and more comfortable for patients than CLC.

Predictors of recurrence after resection of small gastric gastrointestinal stromal tumors of 5 cm or less.

GOALS: To evaluate the recurrence predicting factors of small gastric gastrointestinal stromal tumors (GISTs) through the long-term follow-up after surgical/endoscopic resection. BACKGROUND: Although small gastric GISTs are known to have a low risk of recurrence after complete resection, the prognostic factors are not well known. STUDY: The study retrospectively analyzed the records of 136 patients with primary gastric GISTs of 5 cm or less without metastasis who underwent surgical/endoscopic resection between March 1997 and December 2008 at the Asan Medical Center, and who were followed-up for at least 3 months after resection. Specimens were assessed for tumor size, mitotic index, and microscopic resection margin. Specimen sections were immunohistochemically stained to determine the levels of expression of the cell cycle proteins p53, p16(INK4), pRb, cyclin D1, and Ki-67. DNA was extracted from high-risk tumors to analyze for KIT mutations. RESULTS: Among 136 patients, 5 (3.7%) patients with tumors with a high mitotic index showed recurrence at a median 23 months post resection. None of 14 patients with microscopic positive resection margins showed recurrence during a median follow-up time of 32 months. A high mitotic index was a predictor of recurrence (P<0.001), but that tumor size, method of resection, or margin status were not. In addition, abnormal p53 expression was found to be associated with recurrence (P=0.004). All assessable high-risk tumors had a KIT exon 11 mutation. CONCLUSIONS: Predictors of recurrence of gastric GISTs of 5 cm or less were a high mitotic index and abnormal p53 expression. A positive microscopic resection margin was not associated with recurrence.

Clinical impact of EUS-guided Trucut biopsy results on decision making for patients with gastric subepithelial tumors ≥ 2 cm in diameter.

BACKGROUND: Preoperative pathologic diagnosis of a gastric subepithelial tumor (SET) may improve clinical decision making. However, the clinical impact of EUS-guided Trucut biopsy (EUS-TCB) data on decision making in patients with a gastric SET has not been assessed. OBJECTIVE: To evaluate the impact of EUS-TCB information on the clinical management of patients with a gastric SET. DESIGN: Retrospective review of prospectively collected data. SETTING: Tertiary referral center. PATIENTS: Sixty-five patients with gastric SETs 2 cm or larger in diameter. INTERVENTION: EUS-TCB. MAIN OUTCOME MEASUREMENTS: The number of patients for whom treatment plans were changed because of EUS-TCB results. RESULTS: Nine SETs were not punctured by the TCB needle because of technical problems, and we were unable to obtain adequate subepithelial tissue from 19 SETs. Treatment plans were changed for 18 of 65 patients (27.7%). The changes were avoiding unnecessary resection (7 benign SETs ≥ 3 cm in diameter), scheduling for definitive treatment (6 GI stromal tumors and 1 carcinoid tumor), and modifying the surgical field (3 large GI stromal tumors and 1 carcinoma). When we assessed treatment plans relative to tumor location, we found that avoiding unnecessary resection was associated with the presence of cardiac SETs. LIMITATIONS: Retrospective study with a small number of patients. CONCLUSIONS: EUS-TCB changed or influenced management decisions in 18 of 65 patients (27.7%) with gastric SETs. Patients could receive proper and tailored surgery, medical treatment, or surveillance according to size and location of SETs with EUS-TCB.

Comparison of early outcomes of intracorporeal and extracorporeal gastroduodenostomy after laparoscopic distal gastrectomy for gastric cancer.

BACKGROUND: Totally laparoscopic distal gastrectomy (TLDG) has several advantages over laparoscopic-assisted distal gastrectomy (LADG), including a shorter incision, less pain, and earlier recovery. We compared the feasibility and early surgical outcomes of TLDG and LADG in patients with gastric cancer. METHODS: Between September 2008 and December 2009, 180 patients with gastric cancer underwent TLDG with intracorporeal gastroduodenostomy using linear staplers; and between January 2006 and December 2009, 268 patients with gastric cancer underwent LADG with extracorporeal gastroduodenostomy using circular staplers. Clinical features and early surgical outcomes were compared between the two groups. RESULTS: There were no between-group differences in postoperative clinical course and complications. Postoperative pain and the amount of pain killer administered were significantly lower (P<.05 each), and postoperative scars were smaller in the TLDG group. CONCLUSIONS: TLDG with intracorporeal gastroduodenostomy is as safe and feasible as LADG for patients with gastric cancer. Moreover, TLDG is less invasive and more comfortable for patients than LADG.

Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1,414 cases of whole-tissue sections and 595 cases of tissue microarrays.

BACKGROUND: Recent advances in molecular targeted therapy have identified HER2 as an important target for anti-cancer therapy in gastric cancer (GC). Although the clinical relevance and prognostic significance of HER2 in breast cancer has been well acknowledged, it remains controversial in GC. METHODS: HER2 expression was investigated in two independent series of GC by immunohistochemical staining. One series corresponded to 1,414 cases of whole-tissue sections and the other corresponded to 595 cases of tissue microarrays (TMAs). Results were compared and correlated with clinicopathologic parameters. RESULTS: HER2-positivity was detected in 12.3% of whole-tissue sections and 17% of TMAs. Among samples scored 3+, 90.1% stained ≥50% of the tumor area, but only 40.9% in score 2+ cases stained ≥50% of the tumor area. In whole-tissue sections, HER2-positivity was correlated with age (P = 0.002), histological type (differentiated or intestinal, P < 0.001), lymphovascular invasion (P = 0.005), and lymph node metastasis (P = 0.009). In TMAs, HER2-positivity was correlated only with age (P = 0.003) and histological type (P < 0.001). Multivariate analyses of the differentiated GC subgroup revealed that HER2-positivity was an independent poor prognostic factor (P = 0.042). The cases with HER2-positive in ≥50% of the tumor area showed worse prognosis than those of <50% (P = 0.021). CONCLUSIONS: Despite discrepancies in the results from whole-tissue sections and TMAs, HER2 overexpression was positively correlated with aggressive biological behavior and was an independent poor prognostic factor for recurrence in differentiated GCs. Therefore, HER2-positive GCs should be considered for adjuvant trastuzumab therapy.

Typical carcinoids and neuroendocrine carcinomas of the stomach: differing clinical courses and prognoses.

BACKGROUND: Gastric endocrine tumors are usually classified as 3 types of well-differentiated endocrine tumors (typical carcinoids or carcinoids) and poorly differentiated carcinomas (neuroendocrine carcinomas [NECs]). METHODS: From 1993 to 2008, 97 patients (73 men and 24 women) were diagnosed with gastric neuroendocrine tumors at the Asan Medical Center. RESULTS: Of the 45 patients with typical carcinoids, 37 underwent surgery (eg, endoscopic resection). Of the 52 patients with NECs, 43 underwent surgery (eg, radical gastrectomy). One patient died of recurrence of the typical carcinoids, whereas 26 patients with NECs died of related diseases (P < .05). The rates of survival and recurrence did not significantly differ by type of typical carcinoid (P > .05). CONCLUSIONS: Regardless of the type, carcinoids that are not yet advanced can be effectively treated with minimal endoscopic or laparoscopic surgery. However, all NECs and advanced carcinoids should be treated with radical gastrectomy.