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.

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 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.

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.

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.

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.

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.

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.

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.

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.

Neoadjuvant docetaxel, capecitabine and cisplatin (DXP) in patients with unresectable locally advanced or metastatic gastric cancer.

BACKGROUND: This phase II study was conducted to evaluate the efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin and capecitabine (DXP) in patients with unresectable locally advanced and/or intra-abdominal metastatic gastric cancers. METHODS: Patients with advanced gastric cancer (AGC), clinically unresectable because of local invasion or limited intra-abdominal metastasis in para-aortic lymph nodes and/or the peritoneum based on multidetector row computed tomography, were enrolled. DXP consisted of docetaxel 60 mg/m(2) i.v. and cisplatin 60 mg/m(2) i.v. on day 1, and capecitabine 937.5 mg/m(2) twice daily p.o. on days 1-14 every 21 days. Surgery was performed after 4-6 cycles of DXP. RESULTS: Thirty-six (74%) of the 49 patients enrolled underwent surgery, and 31 (63%) had an R0 resection. R0 resection was possible in 15 of 21 patients (71%) with unresectable locally advanced lesions, 12 of 17 patients (70%) with para-aortic lymph node metastasis but only 4 of 11 patients (36%) with peritoneal metastasis. Grade 3/4 toxicities included neutropenia (69%), febrile neutropenia (4%) and hand-foot syndrome (8%). CONCLUSIONS: Neoadjuvant DXP may offer a reasonable chance of curative surgery in AGC patients with unresectable locally advanced or para-aortic lymph node metastasis.

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.

Castleman disease of the abdomen--single-center experience of 13 surgically treated patients over 11 years.

BACKGROUND/AIMS: Castleman disease (CD) is a lymphocytic hyperplastic disease, also known as angiofollicular lymphoid hyperplasia and giant lymph node hyperplasia, which rarely occurs in the abdomen. We analyzed the clinical manifestations in 13 patients treated surgically at our center for abdominal CD lesions. METHODOLOGY: We retrospectively reviewed the medical records of 13 patients with abdominal CD who underwent surgery at our institution in the 11-year period from January 1998 to May 2009. RESULTS: Of the 13 patients, 8 were women; their mean +/- SD age was 47.1 +/- 12.0 years. CD was incidentally found in seven patients with no symptoms. Only 3 patients were preoperatively suspected of CD, with 10 suspected of other diseases. Twelve of the 13 patients (92.3%) underwent excisional surgery, with 11, 1 and 1 undergoing R0, R1, and R2 resections, respectively. Eleven tumors were hyaline vascular type and two were plasma cell type. After a mean follow-up of 63.3 months, only one patient showed recurrence, but this patient remains progression-free 7 years after repeat resection. CONCLUSIONS: Abdominal CD is a rare disease that is often misdiagnosed due to the absence of specific clinical manifestations. Definitive diagnosis requires histologic examination of the surgical specimen. Excisional surgery is the method of choice for unicentric abdominal CD, and is associated with a low incidence of recurrence.

PDGFRalpha gene mutation and protein expression in gastrointestinal stromal tumors.

OBJECTIVE: Mutation of the PDGFRalpha is a potential candidate in the pathogenesis of KIT wild-type gastrointestinal tumors (GISTs). In this study, we evaluated the prevalence of PDGFRalpha mutations and corresponding protein expression in GISTs, to determine their usefulness in obtaining a prognosis. METHODS: Genomic DNA was extracted from paraffin-embedded tumor tissues from 194 GISTs. Exons 12, 14 and 18 of the PDGFRalpha were amplified and sequenced. Immunohistochemical staining was performed in 179 patients. RESULTS: Mutations in the PDGFRalpha were detected in 6 (3.1%) patients, and were observed solely in KIT wild-type GISTs. Among the 6 patients with PDGFRalpha gene mutations, 5 patients with localized GISTs showed no relapse after resection during the 19- to 80-month follow-up period. Intensity of PDGFRalpha expression was classified as 0 in 26 (14.5%), 1+ in 69 (38.5%), 2+ in 71 (39.7%) and 3+ in 13 (7.3%) patients. Levels of PDGFRalpha expression showed no correlation with relapse-free survival. CONCLUSION: PDGFRalpha mutations in GISTs were found to be rare in this Korean population. Although localized GISTs with PDGFRalpha mutations showed relatively good prognosis after resection, the difference was not statistically significant.

A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer after failure of fluoropyrimidine and platinum combination chemotherapy.

PURPOSE: Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used as a first-line treatment of advanced gastric cancer (AGC). Docetaxel has shown promising activity against this disease. In this study, we explored the efficacy and safety of docetaxel monotherapy as salvage chemotherapy in AGC after F and P combination chemotherapy failed. MATERIALS AND METHODS: From October 2004 to October 2005, 49 eligible patients were enrolled in this study. The median treatment-free interval was 28.0 days, and 81.6% of patients had suffered cancer progression within 4 months after the withdrawal of first-line chemotherapy. Docetaxel was given IV at a dose of 75 mg/m(2) every 3 weeks, together with dexamethasone prophylaxis. RESULTS: A total of 182 cycles of docetaxel were administered with a median of 3 (range 1-9) cycles. From an intention-to-treat analysis, eight patients achieved objective response with a response rate of 16.3% (95% CI, 6.0-26.6). The median response duration was 4.7 months. A total of 20 patients showed stable disease, but 17 patients suffered disease progression. At a median follow-up duration of 11.3 months for surviving patients (range 6.3-18.8 months), the median time to disease progression was 2.5 months (95% CI, 2.3-2.7) and the median overall survival time since the start of docetaxel monotherapy was 8.3 months (95% CI, 6.7-9.8). Grade 3/4 neutropenia and febrile neutropenia occurred in 18.4% of patients and in 5.4% of cycles. The incidence of non-hematologic toxicities of grade 3 or worse was asthenia 32.7%, diarrhea 10.2% and peripheral sensory neuropathy 8.2%. CONCLUSION: Docetaxel at 75 mg/m(2) is active against AGC as second-line chemotherapy after prior exposure to F and P combination chemotherapy. The toxicity profile is moderate.

Modified radical lymphadenectomy without splenectomy in patients with proximal gastric cancer: comparison with standard D2 lymphadenectomy for distal gastric cancer.

BACKGROUND AND OBJECTIVES: We assessed the optimal extent of lymph node dissection and the effect of splenectomy in patients with proximal gastric cancer. METHOD: Recurrence and survival rates were compared between 881 patients with proximal gastric cancer who underwent modified radical lymphadenectomy and 3,098 patients with distal gastric cancer who underwent standard D2 lymphadenectomy. RESULTS: The recurrence rate was significantly higher in the total than in the distal gastrectomy group (32.5% vs. 16.5%, P < 0.001), but the rates were similar after adjustment for TNM stage. The overall 5-year survival rate was significantly higher in the distal than in the total gastrectomy group (80.4% vs. 66.2%, P < 0.001), but this difference was not observed after adjustment for TNM stage. Multivariate analysis showed that patient age, number of retrieved lymph nodes, depth of invasion, and nodal metastasis were independent prognostic determinants for survival, whereas type of lymphadenectomy was not. CONCLUSION: Long-term outcomes were similar in patients with proximal gastric cancer who underwent modified lymphadenectomy without splenectomy and in patients with distal gastric cancer who underwent standard D2 lymphadenectomy. These findings indicate that modified radical lymphadenectomy without splenectomy is sufficient for optimal lymph node dissection in patients with proximal gastric cancer.

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.

Aberrant CpG island methylation in early-onset sporadic gastric carcinoma.

PURPOSE: Gastric carcinoma more commonly affects older patients, and it is thought that cases of early-onset gastric carcinoma may develop with a different molecular profile different from that of carcinoma occurring at a later age. We assayed the methylation status and genetic changes in genes associated with the APC-beta-catenin axis and the mismatch repair system in relatively early-onset gastric carcinoma samples to determine their association with gastric carcinogenesis. METHODS: Tumor and normal tissue DNA samples were obtained from 40 patients with early-onset (< 50 y) gastric carcinomas and assayed for APC and CTNNB1 mutations, microsatellite instability, and methylation of the promoters of the hMLH1, TIMP3, THBS1, DAP- K, GSTP1 , APC, and MINT2. RESULTS: Promoter methylation at these seven loci ranged from 12.5 to 62%, with 38/40 tumors (95%) showing promoter methylation at more than one locus. The CpG island methylation phenotype (CIMP) was classified as high in 16 tumors (40%), low in 22 tumors (55%), and negative in 2 tumors (5%). Two concurrent missense mutations (E1685G, R1763L) in the APC mutation cluster region were detected in two tumors, nine tumors showed loss of APC heterozygosity (LOH), and two showed both LOH and promoter methylation. CONCLUSIONS: Our results indicate that, unlike in colorectal carcinoma, APC and CTNNB1 mutations do not appear to be highly implicated in early-onset gastric carcinogenesis. In contrast, our data show that promoter methylation is a prevalent phenomenon in early-onset gastric carcinoma and may be related to gastric carcinogenesis.