Jeong Hwan Yook

Prognostic Significance of c-kit Mutation in Localized Gastrointestinal Stromal Tumors

Purpose: Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial. Experimental Design: We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced. Results: Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count [≥5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (≥5 cm; OR = 4.2). Conclusions: The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs.

Surgical intervention following imatinib treatment in patients with advanced gastrointestinal stromal tumors (GISTs).

We investigated the role of surgical intervention for advanced GIST after imatinib.

Comprehensive analysis of HER2 expression and gene amplification in gastric cancers using immunohistochemistry and in situ hybridization: which scoring system should we use? ☆,☆☆

It has been reported that HER2 expression is different in gastric and breast cancers, and a gastric cancer scoring system (GCSS) has recently been suggested. We investigated HER2 protein expression using GCSS and a breast cancer scoring system (BCSS) and correlated it with HER2 gene amplification. HER2 status was evaluated in 1091 cases by analyzing tissue microarrays constructed using 2 different cores from each case. Polyclonal (HercepTest) and monoclonal (Pathway) antibodies were used for immunohistochemistry (IHC), and results were scored by BCSS and GCSS. Gene amplification was evaluated by automated dual-color silver-enhanced in situ hybridization (SISH) in all cases and correlated with the results from fluorescence in situ hybridization (FISH) in 590 cases. The concordance between the IHC results using polyclonal and monoclonal antibodies was high (κ = 0.785). The results of dual-color SISH and FISH showed very high concordance as well (κ = 0.918). GCSS was significantly more sensitive for detecting SISH positivity than was BCSS in both antibodies (polyclonal, P = .003; monoclonal, P < .001), but specificity was higher in BCSS than GCSS (polyclonal, P = .004; monoclonal, P < .001). It has been recently shown that HER2-overexpressing patients with unresectable gastric cancer benefited from trastuzumab therapy. Because IHC is recommended before gene amplification studies in HER2 testing, GCSS should be used for evaluating HER2 expression in gastric cancers.

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.

Metallic Stent Placement in the Palliative Treatment of Malignant Gastric Outlet Obstructions: Primary Gastric Carcinoma Versus Pancreatic Carcinoma

OBJECTIVE The objective of our study was to compare the clinical effectiveness of metallic stent placement for relief of gastric outlet obstruction caused by gastric carcinoma and pancreatic carcinoma. MATERIALS AND METHODS A total of 207 patients with gastric outlet obstruction caused by inoperable gastric carcinoma (n = 147) or pancreatic carcinoma (n = 60) underwent metallic stent placement. RESULTS Technical success of metallic stent placement was achieved in all patients. Clinical success was achieved in 97% and 93% of patients with gastric and pancreatic carcinoma, respectively (p = 0.286). The overall complication rate did not differ significantly between the gastric (29%) and pancreatic (23%) carcinoma groups (p = 0.441). Stent collapse was significantly more frequent in the gastric carcinoma group (11%) than the pancreatic carcinoma group (2%) (p = 0.027), whereas serious complications, including gastrointestinal bleeding and intestinal perforation, occurred more frequently in the pancreatic (7%) than the gastric (1%) carcinoma group (p = 0.026). The cumulative survival period was significantly longer in the gastric carcinoma (median, 153 days) than the pancreatic carcinoma (median, 90 days) group (p = 0.041), but cumulative stent patency did not differ significantly between the gastric carcinoma (median, 350 days) and pancreatic carcinoma (median, 385 days) groups (p = 0.415). CONCLUSION Metallic stent placement was clinically effective in the palliative treatment of gastric outlet obstruction in patients with gastric and pancreatic carcinoma. The two groups differed significantly in the rates of stent collapse and serious complications and patient survival after stent placement.

Extended indication of endoscopic resection for mucosal early gastric cancer: Analysis of a single center experience

Background:  Endoscopic resection (ER) has become an important therapeutic option for early gastric cancer (EGC). Some investigators have suggested that this indication should be extended. We aimed to compare the extended indication of ER for intramucosal EGC based on data from a large, single‐center study.

Signet ring cell type and other histologic types: Differing clinical course and prognosis in T1 gastric cancer

BACKGROUND The behavior of early stage signet ring cell carcinoma (SRC) is controversial. The purpose of this study was to clarify the behavior of early gastric SRC. METHODS We retrospectively analyzed data from 2,085 patients who had undergone curative gastrectomy for early gastric cancer between 1989 and 2000. Clinicopathologic outcomes and prognoses were evaluated, and we investigated whether these variables were correlated with histopathologic type. RESULTS Patients with early gastric SRC were younger and had a greater proportion of females than other histologic types. Lymph node metastasis was the only independent prognostic factor for both mucosal and submucosal forms of SRC. Mucosal SRC had a similar rate of lymph node metastasis to poorly differentiated (PD) tubular adenocarcinoma (TUB), and a higher rate than well-differentiated (WD) or moderately differentiated (MD)-TUB. However, its submucosal form had a similar rate of lymph node metastasis to WD-TUB, and a lower rate than MD- or PD-TUB. There was no difference in tumor recurrence or disease-related death according to histopathologic type or depth of invasion. CONCLUSION In mucosal gastric cancer, SRC has an unfavorable risk factor of lymph node metastasis than that of others and should not be considered for endoscopic resection. In submucosal gastric cancer, SRC is a more favorable risk factor of lymph node metastasis than that of other histologic types.

Influence of Obesity on Early Surgical Outcomes of Laparoscopic-assisted Gastrectomy in Gastric Cancer

Background The aim of this study is to estimate the impact of obesity on surgical outcomes of laparoscopic-assisted gastrectomy for gastric cancer. Study Design Between January 2005 and January 2010, 1100 consecutive patients who underwent laparoscopic-assisted distal gastrectomy for gastric cancer were reviewed to evaluate the impact of obesity. The patients were classified into 3 groups according to the World Health Organization classification, as normal weight [body mass index (BMI) 18.5 to 24.9 kg/m2], overweight (BMI 25 to 29.9 kg/m2), and obese patients (BMI ≥30 kg/m2). Results The postoperative complication rates for normal weight, overweight, and obese patients were 5.7%, 10.0%, 15.4%, respectively. Overweight and obese patients had a significantly prolonged operation time, increased intraoperative blood loss, prolonged first flatus, day of commencement of soft diet, increased number of administration of analgesics, and prolonged hospital stay. Conclusions Overweight and obesity were associated with poor early surgical outcomes of laparoscopic-assisted gastrectomy. This study suggested that greater cautions and improved surgical techniques were required to improve early surgical outcomes of laparoscopic-assisted gastrectomy for overweight and obese patients.

Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours

Objective Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia. Design Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing. Results We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36×10−12) and non-cardia cancers (p=2.42×10−23) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50×10−8), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47×10−2). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10−8 for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer. Conclusions Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.

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.