Comparative Outcomes in Patients With Small- and Large-Cell Neuroendocrine Carcinoma (NEC) and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm (MiNEN) of the Stomach.

BACKGROUND: Gastric neuroendocrine carcinomas (NECs), consisting of both large- and small-cell NECs, and mixed adenoneuroendocrine carcinomas (MANECs), including mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), are a group of high-grade malignancies. Few studies to date have reported clinical outcomes, including prognosis, in patients with these tumors. This study therefore evaluated the clinicopathologic outcomes and prognosis in patients with NECs and MANECs. METHODS: This study included 36 patients diagnosed with gastric NECs, including 23 with large-cell and 13 with small-cell NECs, and 85 with MiNENs, including 70 with high-grade and 15 with intermediate-grade MiNENs. Clinical outcomes, including overall survival (OS) and disease-free survival (DFS), were assessed. RESULTS: DFS was significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN (P < .05), whereas both OS and DFS were similar in patients with NEC and high-grade MiNEN (P > .05). Patients with large-cell NEC were more likely to undergo aggressive surgery than patients with high-grade MiNEN (P < .05). Lymphovascular invasion was more frequent and DFS poorer in patients with large-cell than small-cell NECs (P < .05 each). CONCLUSION: DFS is significantly poorer in patients with NEC than in patients with intermediate-grade MiNEN and significantly lower in patients with large-cell than small-cell NECs.

Population-based volume kinetics of Ringer's lactate solution in patients undergoing open gastrectomy.

In order to maintain stable blood pressure and heart rate during surgery, anesthesiologists need to administer the appropriate amount of fluid with appropriate fluid type to the patient, then quantifying how fluid is distributed and eliminated from the body is useful for establishing a fluid administration strategy. In this study we characterized the volume kinetics of Ringer's lactate solution in patients undergoing open gastrectomy. When propofol and remifentanil reached a pseudosteady state at the target concentration and blood pressure was stabilized following surgical stimulation, enrolled patients were administered 1000 mL of Ringer's lactate solution for 20 min, followed by continuous infusion at a rate of 6 mL/kg/h until the time of the last blood collection for volume kinetic analysis. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. The change in hemoglobin-derived plasma dilution induced by the administration of Ringer's lactate solution was evaluated by nonlinear mixed effects modeling. Three hundred and twenty-three plasma dilution data points from 27 patients were used to determine the pharmacokinetic characteristics of Ringer's lactate solution. A two-volume model best described the pharmacokinetics of Ringer's lactate solution. The mean arterial pressure (MAP) and body weight (WT) were significant covariates for the elimination clearance (kr) and central volume of distribution at baseline (Vc0), respectively. The parameter estimates were as follows: kr (mL/min) = 124 + (MAP/70)14.2, Vc0 (mL) = 0.95 + 3440 × (WT/63), Vt0 (mL) = 2730, and kt (mL/min) = 181. A higher MAP was associated with a greater elimination clearance and, consequently, less water accumulation in the interstitium. As body weight increases, volume expansion in the blood vessels increases.

Comparison of long-term outcomes of endoscopic submucosal dissection and surgery for esophagogastric junction adenocarcinoma.

BACKGROUND: Endoscopic submucosal dissection (ESD) has become accepted as the standard treatment for early gastric cancer. However, comparative outcomes of ESD and surgery have not been evaluated for adenocarcinoma in the esophagogastric junction (EGJ). We investigated the long-term outcomes of ESD compared with those of surgery for adenocarcinoma in the EGJ. METHODS: Patients who underwent ESD or surgery for Siewert type II adenocarcinoma between 2005 and 2010 and who met the absolute and expanded criteria for endoscopic resection were eligible. Clinical features and treatment outcomes were retrospectively reviewed using medical records. RESULTS: Of the 79 patients included, 40 underwent ESD and 39 underwent surgery. During the median follow-up period of 60.9 months (range, 13.1-125.4 months), the 5-year overall survival rates were 93.9% and 97.3% for the ESD and surgery groups, respectively (p = 0.376). There were no gastric cancer-related deaths in either group. Adverse events occurred in 11 patients (13.9%) overall, and the incidence of treatment-related adverse events was similar between the two groups (10.0% vs. 17.9%, p = 0.308). CONCLUSIONS: ESD may be an effective alternative to surgery for the treatment of early gastric cancer in the EGJ based on the comparable long-term outcomes.

Phase 2 study of adjuvant chemotherapy with docetaxel, capecitabine, and cisplatin in patients with curatively resected stage IIIB-IV gastric cancer.

OBJECTIVE: Postoperative chemotherapy with S-1 or capecitabine plus oxaliplatin is a standard treatment for resectable gastric cancer (GC). However, survival outcomes of stage IIIB-IV (M0) GC cases are still poor. We investigated the efficacy and safety of docetaxel, capecitabine, and cisplatin (DXP) in patients with stage IIIB-IV GC. METHODS: This was a single-arm phase 2 study that included patients with stage IIIB-IV GC who underwent D2 gastrectomy. Patients received six cycles of docetaxel [60 mg/m2 on day 1 (D1)], capecitabine (1,875 mg/m2/day on D1-14), and cisplatin (60 mg/m2 on D1) every 3 weeks. The primary end-point was recurrence-free survival (RFS). RESULTS: A total of 46 GC patients between January 2007 and August 2008 were included. After a median follow-up of 56.1 months (range 52.2-64.1), the median RFS and overall survival (OS) were 26.9 months (95 % CI 7.5-46.4) and 43.9 months (95 % CI 29.2-58.7), respectively. The 5-year RFS and OS rates were 39.1 and 41.3 %, respectively. The most common grade 3/4 toxicities were neutropenia (40 %), anorexia (22 %), and febrile neutropenia (15 %). CONCLUSIONS: Adjuvant DXP is feasible and effective for patients with stage IIIB-IV GC. A phase 3 study comparing triplet and doublet regimens for these patients is ongoing.

Comparison of survival of surgical resection and conservative treatment in patients with gastric cancer aged 80 years or older: a single-center experience.

PURPOSE: With the increase in the average life expectancy, the elderly population continues to increase rapidly. However, no consensus has been reached on the feasibility for surgical resection due to the high morbidity and mortality rate after surgical treatment in elderly patients caused by aging and underlying diseases. METHODS: This study was performed with patients aged 80 years and older. The subjects were classified into 2 groups as follows: the surgical resection group consisting of 61 patients, and the conservative treatment group consisting of 39 patients suitable for curative resection. RESULTS: Mean age and clinical stages in the conservative treatment group were higher than those in the surgical resection group. There was no significant difference in sex, location of the lesion, histological type, or underlying disease. The mean survival time of surgical resection group and conservative treatment group was respectively 52.1 ± 2.66 months and 37.1 ± 5.08 months (P < 0.05) for clinical stage 1 disease, 41.7 ± 5.16 months and 22.4 ± 6.07 months (P = 0.004) for stage 2 disease, and 31.7 ± 9.37 months and 10.6 ± 1.80 months (P = 0.049) for stage 3 disease. However, as for the extent of lymph node resection for the different stages, we observed no significant difference between the 2 groups. CONCLUSION: Surgical resection in all clinical stages, except stage 4, showed a higher survival rate than conservative treatment. To minimize postoperative surgery complications, limited lymph node dissection should also be considered.

Clinical Outcomes of Postoperative Upper Gastrointestinal Leakage According to Treatment Modality.

BACKGROUND & AIM: We evaluated the clinical outcomes according to treatment modality for gastrointestinal anastomotic leakage. METHODS: Of the 19,207 patients who underwent gastrectomy for gastric cancer from March 2000 to April 2013, we retrospectively analyzed the 133 cases who developed anastomotic leakage. These patients were treated using endoscopic management, surgery, or conservative management (endoscopic treatment was introduced in 2009). To evaluate the efficacy of endoscopic treatment, we compared the clinical outcomes between the conservative management-only group before 2009 and the conservative or endoscopic management group from 2009; and between the surgical management-only group before 2009 and the surgical or endoscopic management group from 2009. RESULTS: Seventy-three were initially managed conservatively, 35 were treated surgically, and 25 were treated using endoscopic procedures. Chronologically comparing each treatment group as 'before 2009' (n = 54) and 'from 2009' (n = 79), there were differences in the length of hospital stay (median 32 versus 27, p = 0.048) and duration of antibiotic use (median 28 versus 20, p = 0.013). Patients who underwent conservative or endoscopic management from 2009 showed a shorter hospital stay, period of fasting, and duration of antibiotic use than patients who underwent only conservative management before 2009. Patients who received surgery or endoscopic management from 2009 showed a shorter hospital stay and duration of antibiotic use than patients who underwent only surgery before 2009. CONCLUSION: Endoscopic management for selected cases can reduce duration of hospital stay and antibiotic administration in the treatment of anastomotic leakage after gastrectomy.

Risk factors for selection of patients at high risk of recurrence or death after complete surgical resection in stage I gastric cancer.

BACKGROUND: The therapeutic benefit of adjuvant chemotherapy has not been proven in stage I gastric cancer (GC). The aim of this study was to identify stage I GC patients at high risk of recurrence or death. METHODS: We retrospectively reviewed the medical records of 2,783 patients with pathologically confirmed stage I GC who underwent curative surgical resection alone at Asan Medical Center between 2003 and 2007. The clinicopathologic parameters explored included age, sex, histologic differentiation, Lauren classification, size, location, multiplicity, stage, lymphovascular or perineural invasion, preoperative serum levels of tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4), and type of surgery. RESULTS: With a median follow-up of 54 months (range 0-60 months), 212 patients (7.6%) experienced recurrence or death, and the 5 -year recurrence-free survival (RFS) rate and overall survival rate were 89.9 and 93.4%, respectively. With a multivariate analysis, six factors (age over 65 years, male gender, stage IB GC, lymphovascular invasion, perineural invasion, and elevated level of carcinoembryonic antigen) were independent poor prognostic factors for RFS (p < 0.05). Patients with more than two of six poor risk factors had a 5-year RFS rate of 79%, whereas patients with fewer risk factors had a 5-year RFS rate of 97% (p <0.001). CONCLUSIONS: In this study cohort, we identified six independent risk factors for RFS. The patients with more than two risk factors are expected to have significant risk of recurrence or death after curative resection and should be considered as candidates for adjuvant treatment.

Differing Clinical Courses and Prognoses in Patients With Gastric Neuroendocrine Tumors Based on the 2010-WHO Classification Scheme.

The aim of this study is to test the prognostic accuracy of the 2010-WHO classification for postsurgery survival in nonmetastatic gastric neuroendocrine tumor (NET) cases. Whether the 2010-WHO classification of NETs can predict relapse after surgical resection has not yet been established.We selected 175 nonmetastatic gastric NET patients at Asan Medical Center, Seoul, Korea between 1996 and 2013. All tumors were classified using the WHO-2010 scheme.Among 175 patients with gastric NETs, we diagnosed 39 cases as WHO grade 1, 13 cases as grade 2, 66 cases as grade 3 (neuroendocrine carcinomas; NECs), and 57 cases as mixed with adenocarcinoma. Patients with grade 3 had a lower relapse-free survival (RFS) and overall survival (OS) than those with WHO grade 1/2 and had a lower OS than patients with mixed type tumors. Patients with grade 1/2 had a better OS than patients with mixed type. There was no significant difference in RFS and OS between small and large cell type lesions. Among WHO grade 1/2 patients with ≤1 cm sized lesions, none exhibited lympho-vascular, perineural, mucosal, or submucosal invasion, and we detected no lymph node metastases or recurrences.Our findings strongly suggest that WHO grade 3 behaves more aggressively than adenocarcinoma. Additionally, the survival of cases with large and small cell NEC was similar. Among WHO grade 1/2 patients who had ≤1 cm lesions, none exhibited lympho-vascular, perineural, mucosal, or submucosal invasion and all could be treated by endoscopic resection or minimally invasive surgery without node dissection.

The effects of surgical cytoreduction prior to imatinib therapy on the prognosis of patients with advanced GIST.

BACKGROUND: Baseline tumor size is one of important prognostic factors for imatinib therapy in patients with advanced gastrointestinal stromal tumor (GIST). The purpose of this study was to determine whether surgical cytoreduction before imatinib therapy can improve the prognosis. METHODS: A total of 249 patients with advanced GIST were reviewed retrospectively. Patients were categorized into two groups according to the degree of initial cytoreduction: 35 patients with ≥75 % of initial tumor bulk removed (cytoreduction group) and the other 214 patients (no cytoreduction group). The median follow-up was 44.0 months. RESULTS: Patients in the cytoreduction group were younger, in better performance, showed more initially metastatic disease, peritoneal metastases, but fewer liver metastases. The baseline tumor size when starting imatinib became significantly reduced in the cytoreduction group, which made significant difference between the two groups. By multivariate analyses, mutational status, tumor size, and granulocyte count at presentation were associated with progression-free survival. Age and tumor size were associated with overall survival. However, initial cytoreduction was not significantly related to the prognosis. CONCLUSIONS: Cytoreduction before imatinib therapy appears not to improve the prognosis. Imatinib therapy should still represent the initial treatment for advanced GIST.

Pathologic discordance of differentiation between endoscopic biopsy and postoperative specimen in mucosal gastric adenocarcinomas.

BACKGROUND: Tumor differentiation is a major determinant of endoscopic resection in mucosal gastric cancers, and the treatment decision is usually based on a preoperative endoscopic biopsy. However, in a proportion of patients, the pathologic assessment of differentiation differs between the endoscopic biopsy and postgastrectomy specimen. This discrepancy is important in that it may lead to an additional radical gastrectomy after endoscopic resection or unnecessary operation for patients who could have been treated with endoscopic resection. This study aimed to investigate the frequency of such cases and to identify risk factors for discordance in patients with mucosal gastric adenocarcinoma. METHODS: The clinicopathologic characteristics of 1,326 patients who underwent curative gastrectomy for mucosal gastric cancer at Asan Medical Center from 2007 to 2011 were retrospectively reviewed. RESULTS: The overall discordance was 21.5 % (285 cases), and clinically significant discordant rate was 11.9 % (157 cases). Ninety-nine tumors (7.5 %) with differentiated histology on preoperative biopsy were found to be undifferentiated on postoperative pathology. Additionally, 58 patients (4.4 %) with undifferentiated histology on preoperative biopsy exhibited differentiated histology postoperatively. Multivariate analysis revealed that age, sex, tumor location, size, and gross pattern were associated with overall pathologic discordance. In patients with clinically significant discordance, only tumor location (cardia) and size ([2 cm) were independent factors for discordance. CONCLUSIONS: Considering a high discordance rate of differentiation between biopsy samples and resected specimens in mucosal cancer in cardia, performing endoscopic resection for confirmative diagnosis of differentiation before total gastrectomy can be a good option.

Clinical outcomes of endoscopic and surgical management for postoperative upper gastrointestinal leakage.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of endoscopic therapy, an alternative and less invasive modality for the management of leakage after gastrectomy. METHODS: An electronic database of 35 patients with anastomotic leaks after surgery for stomach cancer that were treated with either an endoscopic procedure or surgery between January 2004 and March 2012 was reviewed. The success rates and safety of both modalities were evaluated. RESULTS: Endoscopic treatment was performed in 20 patients and surgical treatment in 15 patients. The median time interval between the primary surgery and diagnosis of leakage was 8.0 days (interquartile range, 5.0-14.0 days). Of the 20 patients with endoscopic treatment, technical success was achieved in 19 patients (95 %) with resulting clinical success achieved in all of these 19 patients (100 %). One patient with failed endoscopic management went on to receive surgery. There were no cases of leakage-related deaths after endoscopic treatment. Of the 15 patients with surgical treatment, 5 died due to sepsis, bleeding, or hospital-acquired pneumonia. For diagnosis of leakage, 17 patients from the endoscopy group underwent computed tomography (CT) scanning, which revealed leakages in 3 patients (17.6 %) and occult leakages were subsequently defined at fluoroscopy in all 20 patients. Seven of twelve patients (58.3 %) from the surgical group had leakages diagnosed by CT scan. CONCLUSIONS: Endoscopic treatment can be considered a valuable option for the management of postoperative anastomotic leakage with a high degree of technical feasibility and safety, particularly for leakages that are not excessively large.

Serum CA 19-9 as a prognostic factor in patients with metastatic gastric cancer.

AIM: To evaluate tumor markers as prognostic factors in patients with metastatic or recurrent gastric cancer receiving first-line chemotherapy. METHODS: Between January 2000 and December 2008, 1178 patients with metastatic or recurrent gastric cancer were assayed for expression of three serum tumor markers, CA 19-9, CA 72-4 and carcinoembryonic antigen (CEA), prior to the initiation of first-line chemotherapy. RESULTS: Elevated serum concentrations of carbohydrate antigen (CA) 19-9 (>37 U/mL), CA 72-4 (>4 U/mL) and carcinoembryonic antigen (CEA) (>6 ng/mL) were observed in 38, 56 and 33% of patients, respectively. Univariate analysis showed that elevated serum concentration of each of the three markers, CA 19-9 (P = 0.001), CA 72-4 (P = 0.001) and CEA (P = 0.030), was significantly associated with poor patient prognosis. However, multivariate analysis showed that an elevated CA 19-9 concentration only was significantly associated with shorter survival (hazard ratio [HR] 1.22; 95% CI, 1.08-1.37, P = 0.002). In the good risk and moderate risk groups, previously defined by clinical factors alone, survival was significantly lower in patients with elevated CA 19-9 (P < 0.001 and P = 0.021, respectively), but this difference was not observed in the poor-risk group. CONCLUSION: Elevated serum CA 19-9 concentration in patients with metastatic or recurrent gastric cancer, especially in good or moderate risk groups, is an independent negative predictor of prognosis.

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.

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.

EMR versus gastrectomy for intramucosal gastric cancer: comparison of long-term outcomes.

BACKGROUND: Limited data exist regarding the long-term outcomes of EMR compared with gastrectomy. OBJECTIVE: To compare the long-term outcomes after EMR and surgery. DESIGN: Retrospective analysis with propensity-score matching. SETTING: Tertiary care center. PATIENTS: This study involved 215 patients with intramucosal gastric cancer completely removed by EMR and 843 patients who underwent curative surgical resection between January 1997 and August 2002. Propensity-score matching yielded 551 matched patients. INTERVENTIONS: EMR versus surgery. MAIN OUTCOME MEASUREMENTS: Death and recurrence. RESULTS: In the matched cohort, there were no significant between-group differences in the risk of death (hazard ratio [HR] for the EMR group 1.39; 95% CI, 0.87-2.23) or recurrence (HR 1.18; 95% CI, 0.22-6.35). Although patients who underwent EMR had higher risk of metachronous gastric cancers (HR 6.72; 95% CI, 2.00-22.58), all recurrent or metachronous gastric cancers after EMR were successfully re-treated without affecting overall survival. Although complication rates were similar (odds ratio 0.84; 95% CI, 0.41-1.70), there were no mortalities in the EMR group compared with 2 in the surgery group. The EMR group had a significantly shorter hospital stay (median 8 days, interquartile range [IQR] 6-11 days vs 15 days, IQR 12-19 days; P<.001) and lower cost of care ($2049, IQR $1586-2425 vs $4042, IQR $3458-4959; P<.001). LIMITATIONS: Retrospective, nonrandomized study. CONCLUSIONS: EMR was comparable to surgery in terms of risk of death and recurrence. Because of its lower medical costs and shorter duration of hospital stay, EMR has advantages over surgery.

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. METHODS: We assessed lymph node metastasis (LNM) status in 1721 intramucosal EGC patients who underwent surgery to evaluate the potential of extension of the ER. We investigated LNM according to Japanese extended criteria; differentiated mucosal cancers irrespective of ulcer less than 30 mm (Criteria I); differentiated mucosal cancers without ulceration irrespective of tumor size (Criteria II), undifferentiated less than 20 mm without ulceration (Criteria III). We also tried to find the groups which have no and minimal risk of lymph node metastasis. RESULTS: The rate of LNM of mucosal cancer was 2.6% (45/1721). There was minimal lymph nodal metastasis risk for criteria I (0.28%, 2/726, 95% Confidence Interval [CI], 0-0.66%), and criteria II (0.23%, 2/882, 95% CI, 0-0.54%). For criteria III, there was significant lymph node metastasis risk (1.15%, 3/261, 95% CI, 0-2.44%). There was no lymph node metastasis in differentiated mucosal cancer less than 20 mm irrespective of ulcer (0%, 0/501, 95% CI 0-0.73%). The differentiated mucosal cancer group irrespective of ulcer and tumor size have a minimal risk of metastasis (0.43%, 4/941, 95% CI, 0-0.84%) CONCLUSION: Our data support extension of the ER indication for the differentiated mucosal EGC. However, undifferentiated lesions without ulceration and smaller than 20 mm were associated with significant metastasis.

Phase I/II study of a combination of docetaxel, capecitabine, and cisplatin (DXP) as first-line chemotherapy in patients with advanced gastric cancer.

BACKGROUND: This study was conducted to determine the optimal dosage of the docetaxel-capecitabine-cisplatin (DXP) regimen and to evaluate its efficacy and safety in patients with advanced gastric cancer. METHODS: Patients with advanced gastric or esophagogastric junctional adenocarcinoma received capecitabine (days 1-14) and intravenous docetaxel and cisplatin (day 1) every 3 weeks. RESULTS: In the phase I study, 15 patients were treated with 4 different dose levels. Asthenia and neutropenic fever were the dose-limiting toxicities. For the phase II study, 1,125 mg/m(2) of capecitabine was initially recommended with 60 mg/m(2) docetaxel and 60 mg/m(2) cisplatin. However, frequent dose modifications at this dose level resulted in a final optimal dose of 937.5 mg/m(2) capecitabine. Among the 40 patients enrolled in the phase II study, 4 complete and 23 partial responses were observed, presenting objective response rate of 68%. Ten patients achieving good response with complete disappearance of distant metastases underwent surgery, and 4 pathologic complete responses were identified. After the median follow-up of 83.7 months (range, 20.2-86.5) in surviving patients, the median overall survival was 14.4 months and median progression-free survival was 7.6 months. The most frequent grade 3/4 adverse events were neutropenia (62.5%) and asthenia (37.5%). Ten per cent of the patients experienced neutropenic fever, with one case of sepsis-induced death. CONCLUSION: DXP displays considerable antitumor activity, and may thus present effective first-line treatment for advanced gastric cancer. Further investigation of the efficacy and safety of this regimen in both first-line and neoadjuvant settings is warranted.

Clinicopathologic characteristics of colorectal cancer patients with synchronous and metachronous gastric cancer.

BACKGROUND: We investigated the characteristics of synchronous and metachronous gastric cancer in patients with colorectal cancer. METHODS: We reviewed 8,680 patients who underwent operations for primary sporadic colorectal cancer from 1989 to 2008. Synchronous gastric cancer was defined as gastric cancer diagnosed within 6 months of a colorectal cancer diagnosis. Gastric cancer diagnosed more than 6 months before or after colorectal cancer was defined as metachronous. RESULTS: The incidences of synchronous and metachronous gastric cancer were 0.93 and 1.4%, respectively (combined 2.4%). The standardized incidence ratio was 1.199 (95% confidence interval [CI] = 1.005-1.420) when the patients with premetachronous gastric cancer were excluded. Patients with synchronous and metachronous gastric cancer were 5 years older on average compared to the control population without gastric cancer. In addition, multivariate analysis revealed an odds ratio (OR) of 3.6 for being male, OR = 2 for positive family history of solid tumors, OR = 2.2 for colonic lesion, and OR = 4 for MSH2 expression loss compared to patients without gastric cancer. Patients with postmetachronous gastric cancer (when compared to synchronous and premetachronous gastric cancer), a preoperative CEA level of less than 6 ng/ml, and a relatively early stage of colorectal cancer had significantly higher overall (p = 0.016, 0.007, and 0.004, respectively) and disease-free survival rates (p = 0.046, 0.003, and 0.004, respectively), only on univariate analysis. Lymphovascular invasion of colorectal cancer and an advanced stage of gastric cancer were independent poor prognostic factors for both overall (p = 0.018) and disease-free survival (p = 0.028). CONCLUSIONS: Gastric cancer surveillance is recommended for patients with colorectal cancer, especially when the patient is old and male, has a positive family history of solid tumors, has a colonic lesion, or lacks MSH2 expression.

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.