Purpose: Mucin 1 (MUC1) was identified as a gastric cancer (GC) susceptibility gene by genome-wide association studies in Asians and candidate gene studies in Europeans. This study aimed to investigate the association between the MUC1 rs4072037 polymorphism and GC in terms of the Lauren classification and long-term clinical outcomes. Materials and Methods: A total of 803 patients with GC and 816 unrelated healthy controls were enrolled in the study. The association between the MUC1 rs4072037 variant and GC histological types and clinical outcomes, including tumor recurrence and prognosis was investigated. Results: The major A allele of rs4072037 was associated with increased GC risk (P<0.05). In subtype analysis, the association was most significant for diffuse-type GC (P<0.05) and in a dominant model (P<0.05), whereas there was no association with intestinal-type GC (P>0.05). Cox proportional hazards analysis revealed the heterozygote AG rs4072037 allele as an independent risk factor influencing tumor recurrence and disease-related death in diffuse-type GC (P<0.05). but not in intestinal-type GC (P>0.05). Conclusions The exonic single nucleotide polymorphism rs4072037 in MUC1 was associated with diffuse-type GC and was an independent risk factor influencing tumor recurrence and disease-related death in diffuse-type GC.

Purpose: For unresectable or initially metastatic gastric cancer, conversion surgery (CVS), after systemic chemotherapy, has received attention as a treatment strategy. This study evaluated the prognostic value of ypTNM stage and the oncologic outcomes in patients receiving CVS. Materials and Methods: A retrospective review of clinicopathologic findings and oncologic outcomes of 116 patients who underwent CVS with curative intent, after combination chemotherapy, between January 2000 and December 2015, has been reported here. Results: Twenty-six patients (22.4%) underwent combined resection of another organ and 12 patients received para-aortic lymphadenectomy (10.3%). Pathologic complete remission (CR) was confirmed in 11 cases (9.5%). The median overall survival (OS) and disease-free survival (DFS) times were 35.0 and 21.3 months, respectively. In multivariate analysis, ypTNM stage was the sole independent prognostic factor for DFS (P=0.042). Tumors invading an adjacent organ or involving distant lymph nodes showed better survival than those with peritoneal seeding or solid organ metastasis (P=0.084). Kaplan-Meier curves showed that the 3-year OS rate of patients with pathologic CR and those with CR of the primary tumor but residual node metastasis was 81.8% and 80.0%, respectively. OS was 65.8% for stage 1 patients, 49.8% for those at stage 2, and 36.3% for those at stage 3. Conclusions The ypTNM staging is a significant prognostic factor in patients who underwent CVS for localized unresectable or stage IV gastric cancers. Patients with locally advanced but unresectable lesions or with tumors with distant nodal metastasis may be good candidates for CVS.

PURPOSE: The overlap method is one of the most popular procedures for construction of an esophagojejunostomy and its common entry is usually closed with sutures. This study aimed to report long-term complications and surgical outcomes of the overlap method with stapled closure (OMSC), to compare them with those of laparoscopy-assisted total gastrectomy (LATG), and to analyze a learning curve.METHODS: Between January 2015 and August 2017, 100 consecutive patients underwent laparoscopic total gastrectomy with OMSC for gastric cancer and the patients' medical records were reviewed. Their clinicopathologic characteristics, surgical outcomes, and long-term complications were investigated and compared with those of the LATG group. A learning curve of OMSC was analyzed using the Exponentially Weighted Moving Average chart.RESULTS: The overall duration of surgery was shorter in the LATG group; however, there was no difference in patients with early gastric cancer. Hospital admission was shorter and the pain scale was lower in the OMSC group. There was no difference in the number of harvested lymph nodes, date of flatus, or incidence of postoperative morbidity. Both groups showed no duodenal stump leakage, anastomosis-related complications, recurrence, or mortality during the follow-up period. Petersen hernia was a notable long-term event following OMSC compared with LATG. At least 27 cases of surgery were required to reach a plateau in terms of surgery duration for OMSC.CONCLUSION: OMSC is a safe option for the treatment of gastric cancer and has favorable long-term results and surgical outcomes. Closure of mesenteric defects and Petersen space should be considered.
Flatulence ; Follow-Up Studies ; Gastrectomy ; Hernia ; Humans ; Incidence ; Learning Curve ; Lymph Nodes ; Medical Records ; Methods ; Mortality ; Recurrence ; Stomach Neoplasms ; Sutures

PURPOSE: This study aimed to establish a large-scale database of patients with gastric cancer to facilitate the development of a national-cancer management system and a comprehensive cancer control policy. MATERIALS AND METHODS: An observational prospective cohort study on gastric cancer was initiated in 2010. A total of 14 cancer centers throughout the country and 152 researchers were involved in this study. Patient enrollment began in January 2011, and data regarding clinicopathological characteristics, life style-related factors, quality of life, as well as diet diaries were collected. RESULTS: In total, 4,963 patients were enrolled until December 2014, and approximately 5% of all Korean patients with gastric cancer annually were included. The mean age was 58.2±11.5 years, and 68.2% were men. The number of patients in each stage was as follows: 3,394 patients (68.4%) were in stage IA/B; 514 patients (10.4%), in stage IIA/B; 469 patients (9.5%), in stage IIIA/B/C; and 127 patients (2.6%), in stage IV. Surgical treatment was performed in 3,958 patients (79.8%), endoscopic resection was performed in 700 patients (14.1%), and 167 patients (3.4%) received palliative chemotherapy. The response rate for the questionnaire on the quality of life was 95%; however, diet diaries were only collected for 27% of patients. CONCLUSIONS: To provide comprehensive information on gastric cancer for patients, physicians, and government officials, a large-scale database of Korean patients with gastric cancer was established. Based on the findings of this cohort study, an effective cancer management system and national cancer control policy could be developed.
Cohort Studies* ; Diet ; Drug Therapy ; Humans ; Korea ; Male ; Occupational Groups ; Prospective Studies* ; Quality of Life ; Stomach Neoplasms*

BACKGROUND/AIMS: Pregnancy-associated gastric cancer is a rare condition. This case-control study was performed to identify the clinicopathological features and prognostic factors of pregnancy-associated gastric cancer. METHODS: All consecutive patients who presented to our tertiary referral hospital with pregnancy-associated gastric cancer from 1991 to 2012 were identified. Two age-, sex-, and stage-matched controls for each case were also identified from the records. Clinicopathological, gynecological, and oncological outcomes were recorded. Immunohistochemical staining was performed for estrogen receptor, progesterone receptor, epidermal growth factor receptor, human epidermal growth factor receptor, and E-cadherin. Fluorescence in situ hybridization was performed for fibroblast growth factor receptor 2. RESULTS: The median overall survival rates of the pregnancy-associated gastric cancer and control groups were 7.0 months and 15.0 months, respectively (p=0.189). Poor prognostic factors included advanced stage and tumor location in the corpus or the entire stomach but not pregnancy status or loss of E-cadherin. Pregnancy-associated gastric cancer was associated with a longer time from diagnosis to treatment (21 days vs 7 days, p=0.021). The two groups did not differ in the expression of the receptors or E-cadherin. CONCLUSIONS: The dismal prognosis of pregnancy-associated gastric cancer may related to the tumor stage and location rather than to pregnancy itself.
Cadherins ; Case-Control Studies* ; Diagnosis ; Estrogens ; Fluorescence ; Humans ; In Situ Hybridization ; Pregnancy ; Prognosis* ; Receptor, Epidermal Growth Factor ; Receptor, Fibroblast Growth Factor, Type 2 ; Receptors, Progesterone ; Stomach ; Stomach Neoplasms* ; Survival Rate ; Tertiary Care Centers

OBJECTIVES: The aim of our study was to investigate association of norepinephrine transporter gene (SLC6A2) polymorphism and side effects of osmotic-release oral system methylphenidate (OROS MPH) in children with attention-deficit hyperactivity disorder (ADHD). METHODS: We recruited drug naive children with ADHD (N=97). We administered OROS MPH by tolerable dosage. At week 8 of treatment, parents completed the Barkley's side effect rating scale. We analyzed two SLC6A2 single nucleotide polymorphisms (SNPs), rs192303 and rs3785143, with blood of subjects. We compared the frequency and severity of each side effect among SLC6A2 genotypes of 2 SNPs. RESULTS: In the analysis of frequency of each side effect, irritability differed according to rs192303 and rs3785143 genotype. In comparisons of severity, talking less and disinterest differed according to rs192303 genotype. In the case of rs3785143, severities of disinterest and irritability were involved with genotype. CONCLUSION: Side effects of OROS MPH showed an association with SLC6A2 genotype.
Child ; Genotype ; Humans ; Methylphenidate* ; Norepinephrine Plasma Membrane Transport Proteins* ; Parents ; Polymorphism, Single Nucleotide

Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.
Exons ; Follow-Up Studies ; Gastrointestinal Stromal Tumors* ; Humans ; Liver ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Pathology ; Recurrence ; Stomach* ; Imatinib Mesylate

PURPOSE: Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the first line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease. The present study retrospectively investigated the efficacy of D monotherapy as salvage chemotherapy for AGC that is failing F and P combination chemotherapy. MATERIALS AND METHODS: A total of 34 patients, fitting the eligibility criteria, were included in this study. D was administered at a dose of 75 mg/m2 IV every 3 weeks, with dexamethasone prophylaxis. Twenty-nine patients had measurable lesions. The median treatment-free interval was 38.5 days, and 91.2% of patients had progressed within 4 months of withdrawal of the first line chemotherapy. RESULTS: A total of 133 cycles of D were administered, with a median of 3.5 (1~8) cycles. From an intention-to-treat analysis, 6 patients achieved partial responses (PR), with a response rate of 20.7% (95% CI, 6.0~35.4). The duration of objective PRs in these six were 2.3+, 2.5+, 2.9, 3.0+, 6.2 and 6.8 months, respectively. Six patients showed a stable disease, but 15 showed progression. The median time to progression was 4.2 months (95% CI, 2.8~5.5), with a median overall survival since the start of D monotherapy of 8.4 months (95% CI, 5.5~11.3). Grade 3/4 neutropenia and febrile neutropenia occurred in 12.9% of patients and 3.1% of cycles. The incidence of grade 3 or worse non-hematological toxicities were as follows; peripheral sensory neuropathy 9.7%, asthenia 3.2% and allergic reaction 2.7%. CONCLUSION: Docetaxel, 75 mg/m2, is active in AGC as second-line chemotherapy after failure of prior exposure to the F and P combination chemotherapy, with a favorable toxicity profile.
Asthenia ; Dexamethasone ; Drug Therapy* ; Drug Therapy, Combination* ; Febrile Neutropenia ; Humans ; Hypersensitivity ; Incidence ; Neutropenia ; Platinum* ; Retrospective Studies ; Salvage Therapy ; Stomach Neoplasms*

PUPOSE: The superficial spreading type of early gastric cancer has different clinicopathologic features from other types of early gastric cancer in terms of its invasiveness and lymph-node metastases. Therefore, we attempted to elucidate the pathological features, surgical procedures and patients prognoses. MATERIALS AND METHODS: Clinical information was reviewed for patients who had undergone a gastrectomy for gastric cancer during an 8-year period (1995~2002) at Dankook University Hospital and Ulsan University, with an average follow-up of 48 months. Three hundred (300) superficial spreading lesions were analyzed with respect to macroscopic type, lymph-node (LN) metastasis, recurrent pattern, survival rate and method of surgical operation. In addition, the clinicopathological features of the superficial spreading type were compared with those of 739 other patients with small-sized cancer. RESULTS: In both groups, the IIc-type macroscopic lesion, the elevated subtype to be more specific, occurred most frequently. There was no significant difference in the method of surgery between the groups. The submucosal invasion was 39.8% in small-sized cancer, and 61.7% in superficial spreading cancer (P=0.005). The incidence of LN metastasis was 11.3% in early gastric cancer, 7.8% in small-sized cancer and 20.0% in superficial spreading cancer (P=0.005). The incidence of lymphatic invasion was 4.6% in small-sized cancer and 13.0% in superficial spreading cancer (P=0.009). The incidence of recurrence was 1.4% in small-sized cancer and 3.6% in superficial spreading cancer. The overall 5-year survival rate was 84.8% in superficial spreading cancer and 93.0% in small-sized cancer (P=0.052). The 5-year disease- free survival rate was 94.7% in superficial spreading cancer and 87.5% in small-sized cancer (P=0.053). CONCLUSION: The superficial spreading type of early gastric cancer tends to be more invasive and to show a higher incidence of lymph-node metastasis than small-sized early gastric cancer. A wide resection with extensive lymph-node dissection seems to be an appropriate treatment for a superficial spreading type of early gastric cancer.
Follow-Up Studies ; Gastrectomy ; Humans ; Incidence ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Stomach Neoplasms* ; Survival Rate ; Ulsan

PURPOSE: Gastrointestinal stromal tumor (GIST) is the designation for c-kit signal driven mesenchymal tumor. A great majority of these tumors occur in the stomach and small intestine, and rarely in the colon, rectum and esophagus. Metastatic or recurrent GIST must be resected surgically because it is resistant to conventional cytotoxic chemotherapy. Following recent evidence for the dramatic effect of Imatinib mesylate (Glivec), Glivec has become available in our country since June 2001 without insurance coverage. Although some doubt remained, we applied Glivec to recurrent GIST patients with great expectation. METHODS: A retrospective analysis was made for 16 GIST patients who were resected during 2001. Follow up duration was 19 to 29 months. All pathologic slides were reexamined immunohistochemically by an experienced pathologist. Clinicopathologic comparison between the recurred and non-recurred groups was summarized into the tables. The therapeutic and side effects of Glivec were surveyed. CT scan files were reviewed to decided tumor regression or progression. RESULTS: Fifteen GISTs were resected in 2001. Seven cases recurred during 19 to 29 months of follow up. The recurred group was characterized by huge tumor size (mean 14 cm), serosal invasion and more than 10 mitosis in 50 HPF. A daily dose of 400 mg of Glivec was prescribed to every recurred GIST patients and CT scan was followed serially. The therapeutic effect of Glivec effect was drastic but variable; complete tumor remission (n=3), rebounded tumor growth at the same location after remission (n=1), and recurrence at another location after complete remission (n=2). CONCLUSION: Glivec drastically reduced the size of recurrent gastric GIST initially. However, it is not clear how long Glivec should be taken at a great expense in fear of rebounded growth after abstaining. It appears that reoperation is necessary without delay when tumor remission slows down.
Colon ; Drug Therapy ; Esophagus ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; Humans ; Imatinib Mesylate ; Insurance Coverage ; Intestine, Small ; Mesylates* ; Mitosis ; Rectum ; Recurrence ; Reoperation ; Retrospective Studies ; Stomach ; Tomography, X-Ray Computed