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1.
JAMA Netw Open ; 6(2): e2256004, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36790808

ABSTRACT

Importance: Patients undergoing proximal gastrectomy (PG) with double-tract reconstruction (DTR) have been reported to have an incidence of reflux esophagitis that is as low as that observed after total gastrectomy (TG). It is unclear whether PG has an advantage over TG for the treatment of patients with upper early gastric cancer (GC). Objective: To evaluate the effect of laparoscopic PG with DTR (LPG-DTR) vs laparoscopic TG (LTG) on levels of hemoglobin and vitamin B12 supplementation required among patients with clinically early GC in the upper third of the stomach (upper-third early GC). Design, Setting, and Participants: This multicenter open-label superiority randomized clinical trial was conducted at 10 institutions in Korea. A total of 138 patients with upper-third cT1N0M0 GC were enrolled between October 27, 2016, and September 9, 2018. Follow-up ended on December 3, 2020. Interventions: Patients were randomized to undergo either LPG-DTR or LTG. Main Outcomes and Measures: The primary co-end points were change in hemoglobin level and cumulative amount of vitamin B12 supplementation at 2 years after LPG-DTR or LTG. The secondary end points included morbidity, postoperative reflux esophagitis, quality of life, overall survival, and disease-free survival. Quality of life outcomes were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) 30-item core questionnaire (C30) and the EORTC QLQ stomach cancer-specific questionnaire at 3 months, 12 months, and 24 months. Results: Among 138 patients (mean [SD] age, 60.0 [10.9] years; 87 men [63.0%]; all of Asian race and Korean ethnicity), 68 (mean [SD] age, 56.7 [10.4] years; 39 men [57.4%]) were randomized to receive LPG-DTR and 69 (mean [SD] age, 61.3 [11.3] years; 48 men [69.6%]) were randomized to receive LTG. The mean (SD) changes in hemoglobin levels from baseline to month 24 were -5.6% (7.4%) in the LPG-DTR group and -6.9% (8.3%) in the LTG group, for an estimated difference of -1.3% (95% CI, -4.0% to 1.4%; P = .35). The mean (SD) cumulative amount of vitamin B12 supplementation was 0.4 (1.3) mg in the LPG-DTR group and 2.5 (3.0) mg in the LTG group, for an estimated difference of 2.1 mg (95% CI, 1.3-2.9 mg; P < .001). The late complication rates in the LPG-DTR and LTG groups were 17.6% and 10.1%, respectively (P = .31). The incidence of reflux esophagitis was not different between the LPG-DTR and LTG groups (2.9% vs 2.9%; P = .99). Compared with the LTG group, the LPG-DTR group had better physical functioning scores (85.2 [15.6] vs 79.9 [19.3]; P = .03) and social functioning scores (89.5 [17.9] vs 82.4 [19.4]; P = .03) on the EORTC QLQ-C30. Two-year overall survival (98.5% vs 100%; P = .33) and disease-free survival (98.5% vs 97.1%; P = .54) did not significantly differ between the LPG-DTR vs LTG groups. Conclusions and Relevance: In this study, patients with upper-third early GC who received LPG-DTR required less vitamin B12 supplementation than those who received LTG, with no increase in complication rates and no difference in overall and disease-free survival rates. There was no difference in change in hemoglobin level between groups. In addition, the LPG-DTR group had better physical and social functioning than the LTG group. These findings suggest that LPG-DTR may be as safe as LTG and may be a function-preserving procedure for the treatment of patients with upper-third early GC. Trial Registration: ClinicalTrials.gov Identifier: NCT02892643.


Subject(s)
Laparoscopy , Stomach Neoplasms , Humans , Male , Middle Aged , Dietary Supplements , Gastrectomy/methods , Hemoglobins , Laparoscopy/adverse effects , Quality of Life , Stomach Neoplasms/surgery , Treatment Outcome , Vitamin B 12/therapeutic use , Female
2.
Future Oncol ; 18(20): 2465-2473, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35535555

ABSTRACT

Standard-of-care for resectable gastric/gastroesophageal junction cancer includes surgery and neoadjuvant-adjuvant 5-fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) chemotherapy. Early-phase clinical studies support further clinical development of the immune checkpoint inhibitor (ICI); durvalumab, an anti-PD-L1 antibody, in patients with gastric/gastroesophageal junction cancer. Accumulating evidence indicates that ICIs combined with FLOT chemotherapy improve clinical outcomes in patients with advanced or metastatic cancer. We describe the rationale for and the design of MATTERHORN, a randomized, double-blind, placebo-controlled, phase III study investigating the efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy followed by adjuvant durvalumab monotherapy in patients with resectable gastric/gastroesophageal junction cancer. The planned sample size is 900 patients, the primary end point is event-free survival and safety and tolerability will be evaluated. Clinical trial registration: NCT04592913 (ClinicalTrials.gov).


Subject(s)
Adenocarcinoma , Stomach Neoplasms , Adenocarcinoma/pathology , Antibodies, Monoclonal , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Clinical Trials, Phase III as Topic , Esophagogastric Junction/pathology , Fluorouracil/adverse effects , Humans , Neoadjuvant Therapy , Randomized Controlled Trials as Topic , Stomach Neoplasms/pathology
3.
Nat Commun ; 13(1): 774, 2022 02 09.
Article in English | MEDLINE | ID: mdl-35140202

ABSTRACT

Genomic profiling can provide prognostic and predictive information to guide clinical care. Biomarkers that reliably predict patient response to chemotherapy and immune checkpoint inhibition in gastric cancer are lacking. In this retrospective analysis, we use our machine learning algorithm NTriPath to identify a gastric-cancer specific 32-gene signature. Using unsupervised clustering on expression levels of these 32 genes in tumors from 567 patients, we identify four molecular subtypes that are prognostic for survival. We then built a support vector machine with linear kernel to generate a risk score that is prognostic for five-year overall survival and validate the risk score using three independent datasets. We also find that the molecular subtypes predict response to adjuvant 5-fluorouracil and platinum therapy after gastrectomy and to immune checkpoint inhibitors in patients with metastatic or recurrent disease. In sum, we show that the 32-gene signature is a promising prognostic and predictive biomarker to guide the clinical care of gastric cancer patients and should be validated using large patient cohorts in a prospective manner.


Subject(s)
Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Stomach Neoplasms/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil/therapeutic use , Gastrectomy , Gene Expression Profiling , Humans , Kaplan-Meier Estimate , Prognosis , Retrospective Studies , Risk Factors , Stomach Neoplasms/pathology , Transcriptome
4.
Oncotarget ; 8(24): 38389-38398, 2017 Jun 13.
Article in English | MEDLINE | ID: mdl-28418920

ABSTRACT

We tested the clinical utility of combined profiling of Ion Torrent PGM based next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to molecularly targeted therapies. A consecutive cohort of 93 patients with advanced/metastatic GC who underwent palliative chemotherapy between March and December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53 protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay). Treatment was based on availability of targeted agents at the time of molecular diagnosis. Among the 81 cases with available tumor samples, complete NGS and IHC profiles were successfully achieved in 66 cases (81.5%); only IHC results were available for 15 cases. Eight cases received matched therapy based on sequencing results; ERBB2 amplification, trastuzumab (n = 4); PIK3CA mutation, Akt inhibitor (n = 2); and FGFR2 amplification, FGFR2b inhibitor (n = 2). Eleven cases received matched therapy based on IHC; ERBB2 positivity, trastuzumab (n = 5); PTEN loss (n = 2), PI3Kß inhibitor; MMR deficiency (n = 2), PD-1 inhibitor; and EGFR positivity (n = 2), pan-ERBB inhibitor. A total of 19 (23.5%) and 62 (76.5%) cases were treated with matched and non-matched therapy, respectively. Matched therapy had significantly higher overall response rate than non-matched therapy (55.6% vs 13.1%, P = 0.001). NGS and IHC markers provide complementary utility in identifying patients who may benefit from targeted therapies.


Subject(s)
Biomarkers, Tumor/analysis , High-Throughput Nucleotide Sequencing/methods , Immunohistochemistry/methods , Molecular Targeted Therapy/methods , Stomach Neoplasms/drug therapy , Adult , Aged , Biomarkers, Tumor/genetics , Feasibility Studies , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality
5.
J Am Coll Surg ; 224(4): 546-555, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28017807

ABSTRACT

BACKGROUND: Gastric adenocarcinoma is an aggressive disease with frequent lymph node (LN) metastases for which lymphadenectomy results in a survival benefit. In the US, the National Comprehensive Cancer Network guidelines recommend D2 lymphadenectomy or a minimum of 15 LNs retrieved. However, retrieval of only 15 LNs is considered by most international guidelines as inadequate. We sought to evaluate the survival benefits associated with a more complete lymphadenectomy. STUDY DESIGN: An international database was constructed by combining gastric cancer cases from the Surveillance, Epidemiology, and End Results program database (n = 13,932) and the Yonsei University Gastric Cancer database (n = 11,358) (total n = 25,289). Kaplan-Meier survival analysis was performed along with Joinpoint analysis to obtain the optimal number of LNs to retrieve based on survival. Prognostic significance of number of nodes retrieved was then confirmed with univariate and multivariate analyses. RESULTS: Analysis for both mean and median survival yielded 29 LNs removed as the Joinpoint. This was confirmed with multivariate analysis, where 15 retrieved LNs cutoff fell out of the model and 29 retrieved LNs remained intact, with a hazard ratio of 0.799 (95% CI 0.759 to 0.842; p < 0.001). Stage-stratified Kaplan-Meier analysis for a cutoff point of 29 LNs also demonstrated a statistically significant improvement in survival. CONCLUSIONS: Joinpoint analysis has allowed for the creation of a model demonstrating the point at which additional dissection would not provide additional benefit. This large international dataset analysis demonstrates that the maximal survival advantage is seen by performing a lymphadenectomy with a minimum of 29 LNs retrieved.


Subject(s)
Adenocarcinoma/surgery , Gastrectomy , Lymph Node Excision/methods , Stomach Neoplasms/surgery , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Databases, Factual , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Prognosis , SEER Program , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Treatment Outcome , Young Adult
6.
Radiology ; 275(1): 196-204, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25474180

ABSTRACT

PURPOSE: To validate the usefulness of a newly developed tracer for preoperative gastric sentinel lymph node (LN) (SLN) mapping and intraoperative navigation after a single preoperative submucosal injection in rat and beagle models. MATERIALS AND METHODS: This study was approved by the Experimental Animal Ethical Committee of Yonsei University College of Medicine according to the eighth edition of the Guide for the Care and Use of Laboratory Animals published in 2011. An emulsion was developed that contained indocyanine green in iodized oil, which can be visualized with both computed tomography (CT) and near-infrared (NIR) optical imaging and has the property of delayed washout. This emulsion was injected into the footpad of rats (n = 6) and the gastric submucosa of beagles (n = 8). CT lymphography was performed. The degree of enhancement of popliteal LNs was measured in rats, and the enhancing LNs were identified and the degree of enhancement of the enhancing LNs was measured in beagles. Next, NIR imaging was performed in beagles during open, laparoscopic, and robotic surgery to identify LNs containing the fluorescent signals of indocyanine green. The enhanced LNs detected with CT lymphography and NIR imaging were matched to see if they corresponded. RESULTS: Preoperative CT lymphography facilitated SLN mapping, and 26 SLNs were identified in eight beagles. NIR imaging enabled high-spatial-resolution visualization of both SLNs and the intervening lymphatic vessels and was useful for intraoperative SLN navigation. CONCLUSION: SLN mapping with fluorescent iodized oil emulsion is effective and feasible for both CT and NIR imaging.


Subject(s)
Emulsions/pharmacokinetics , Ethiodized Oil/pharmacokinetics , Lymphography/methods , Sentinel Lymph Node Biopsy , Stomach Neoplasms/pathology , Tomography, X-Ray Computed/methods , Animals , Disease Models, Animal , Dogs , Emulsions/chemistry , Ethiodized Oil/chemistry , Fluorescent Dyes , Gastrectomy , Hexoses/chemistry , Hexoses/pharmacokinetics , Intraoperative Care , Laparoscopy , Lymph Node Excision , Male , Polysorbates/chemistry , Polysorbates/pharmacokinetics , Radiographic Image Interpretation, Computer-Assisted , Rats , Rats, Sprague-Dawley , Robotics , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Surface-Active Agents/chemistry , Surface-Active Agents/pharmacokinetics
7.
Ann Surg ; 258(6): 964-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23324857

ABSTRACT

OBJECTIVE: Anemia after gastrectomy is commonly neglected by clinicians despite being an important and frequent long-term metabolic sequela. We hypothesized that the incidence and timing of the occurrence of iron deficiency after gastrectomy is closely associated with the extent of gastrectomy and the reconstruction method, and we investigated the treatment outcomes of iron supplementation to understand iron metabolism and determine the optimal reconstruction method after gastrectomy. PATIENTS AND METHODS: Using a prospective gastric cancer database, we identified 381 patients with early gastric cancer with complete hematologic parameters who underwent gastrectomy between January 2004 and May 2008. Kaplan-Meier methods, Cox regression, and logistic regression were used to evaluate the associations of the extent of gastrectomy and reconstruction method with iron metabolism. RESULTS: The prevalence of iron deficiency 3 years after gastrectomy was 69.1%, and iron-deficiency anemia was observed in 31.0% of patients. Iron deficiency developed in 64.8% and 90.5% of patients after distal gastrectomy and total gastrectomy within 3 years after surgery (P < 0.0001), respectively. Iron deficiency was significantly more frequent in women than in men (P < 0.0001) and after gastrojejunostomy than after gastroduodenostomy (P < 0.0001). Serum ferritin levels were different according to the extent of gastrectomy and reconstruction method. The proportion of patients treated for iron-deficiency anemia was also significantly different according to the extent of gastrectomy (P = 0.020). CONCLUSIONS: Iron deficiency occurs in most patients with gastric cancer after gastrectomy, and its incidence was different according to the extent of gastrectomy and reconstruction method. To improve iron metabolism after distal gastrectomy, gastroduodenostomy would be the method of reconstruction whenever possible.


Subject(s)
Gastrectomy/adverse effects , Iron Deficiencies , Iron/metabolism , Stomach Neoplasms/surgery , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/etiology , Anemia, Iron-Deficiency/therapy , Deficiency Diseases/epidemiology , Deficiency Diseases/etiology , Deficiency Diseases/therapy , Dietary Supplements , Digestive System Surgical Procedures/methods , Female , Gastrectomy/methods , Humans , Incidence , Iron/administration & dosage , Male , Middle Aged , Prospective Studies
8.
Surg Endosc ; 26(8): 2267-74, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22350230

ABSTRACT

BACKGROUND: Pretreatment identification of the sentinel lymph nodes (SLNs) in gastric cancer patients may have great advantages for minimally invasive treatment. No reliable method for the detection of SLNs during the pretreatment period in gastric cancer has been established. The aim of this study was to determine whether computed tomographic (CT) lymphography using nanoscale iodized oil emulsion via endoscopic submucosal injection can visualize LNs. METHODS: Five dogs underwent CT lymphography after endoscopic submucosal injection of 2 ml of a nanoscale iodized oil emulsion. CT images were taken before and 30, 90, and 210 min after contrast injection. Intraoperative SLN detection was performed using endoscopically injected indocyanine green lymphography for comparison. RESULTS: Computed tomographic lymphography with nanoscale iodized oil emulsion enabled the visualization of 19 enhanced LNs (mean = 3.8/dog, range = 3-6) with a 100% SLN detection rate. The locations of the SLNs were the lesser curvature (n = 7), greater curvature (n = 1), infrapyloric (n = 3), and left gastric (n = 8) areas. Contrast enhancement of SLNs continuously increased and peaked after 210 min at 142.4 ± 42.3 HU. No green LNs were visualized in the three locations that were detected by CT lymphography. However, no additional LNs were visualized using the dye method. The concordance rate based on the LNs between the SLNs on CT lymphography and the green LNs using the ICG method was 84% (16/19), whereas the concordance rate of the stations identified by CT lymphography and the dye method was 78.6% (11/14). CONCLUSIONS: Computed tomographic lymphography using nanoscale iodized oil emulsion is a promising tool for preoperative SLN detection for early gastric cancer if the biological safety of the nanoscale iodized oil emulsion can be established.


Subject(s)
Contrast Media , Ethiodized Oil , Lymph Nodes/diagnostic imaging , Nanoparticles , Tomography, X-Ray Computed/methods , Animals , Dogs , Hexoses , Lymphography/methods , Male , Polysorbates
9.
Invest New Drugs ; 30(1): 357-63, 2012 Feb.
Article in English | MEDLINE | ID: mdl-20734110

ABSTRACT

BACKGROUND: Although its efficacy is unproven, 5-fluorouracil plus cisplatin (FP) is used to prevent postoperative relapse in gastric cancer. We investigated the safety and feasibility of S-1 plus cisplatin (SP) vs. FP for stage IIIB-IV (M0) gastric cancer. METHODS: Following curative resection, 41 stage IIIB-IV (M0) gastric cancer patients were assigned to SP (eight 14-day cycles of S-1 [40 mg/m(2) twice daily] plus cisplatin [60 mg/m(2) day 1] administered every 3 weeks) or FP (six 3-day cycles of FU [1 g/m(2) per day] plus cisplatin [80 mg/m(2) day 1] every 4 weeks). Doses were reduced based on predefined criteria. RESULTS: Patient characteristics were balanced between the two arms. In total, 124 cycles of SP (N = 20, median = 7, range 1-8) and 113 cycles of FP (N = 21, median 6, range 1-6) were administered. The median relative dose intensity per patient was 75% (49.99-100%) for S-1, 100% (75-100%) for cisplatin in SP, and 100% (64-100%) for 5-FU, 100% (60-100%) for cisplatin in FP. The relative dose intensity of FP was stable, while that of SP decreased during treatment. After median follow-up of 7.9 months (3.8-14.55), the median RFS was not reached. Relapse occurred in two (10%) patients on SP and five (23.8%) in the FP arm (P = 0.24). The incidence of grade 3-4 granulocytopenia was 36.8% with SP and 14.3% with FP. Grade 3-4 non-hematologic toxicities included fatigue (5.2% with SP vs. 4.8% with FP), vomiting (10.5% with SP vs. 0% with FP), and infection (5.2% with SP vs. 0% FP). CONCLUSION: S-1 plus cisplatin was feasible and tolerable as adjuvant treatment for stage IIIB-IV (M0) gastric cancer. However, because of decreased relative dose intensity during treatment, further study is warranted to determine optimal dosage and combination.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gastrectomy , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemotherapy, Adjuvant , Chi-Square Distribution , Cisplatin/administration & dosage , Disease-Free Survival , Drug Combinations , Feasibility Studies , Female , Fluorouracil/administration & dosage , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Oxonic Acid/administration & dosage , Pilot Projects , Republic of Korea , Stomach Neoplasms/pathology , Tegafur/administration & dosage , Time Factors , Treatment Outcome
10.
Int J Cancer ; 131(2): 505-11, 2012 Jul 15.
Article in English | MEDLINE | ID: mdl-21898388

ABSTRACT

This study investigated whether MSI status can be used as a prognostic biomarker and whether it is helpful for predicting which patients will benefit from 5-FU based adjuvant chemotherapy. Between 2005 and 2008, an MSI status examination was performed in 1,990 gastric cancer patients who had undergone curative gastrectomy for gastric adenocarcinoma. MSI was analyzed by PCR amplification with fluorescent dye-labeled primers of mononucleotide markers (BAT25 and BAT26) and dinucleotide markers (D5S346, D2S123 and D17S250) specific to the microsatellite loci. Patients with MSI-H tumors accounted for 8.5% (n = 170) of the total study population. They tended to be older and female and to have distal tumor location, lower tumor stage, intestinal type of Lauren classification and differentiated histological type. The disease-free survival curves showed no significant differences between MSS/MSI-L and MSI-H patients at each stage of I, II, III and IV. In gastric cancer patients with stage II and III, 5-FU-based adjuvant chemotherapy showed better disease-free survival in the MSS/MSI-L group, but showed no benefits in the MSI-H group. By multivariate analysis, patients with MSS/MSI-L tumors benefited from 5-FU-based adjuvant chemotherapy in terms of tumor disease-free survival. MSI status in gastric cancer is not itself a prognostic indicator. However, it appears to be a possible guidance for the use of 5-FU-based chemotherapy in stage II and III gastric cancers after R0 resection.


Subject(s)
Antineoplastic Agents/therapeutic use , Fluorouracil/therapeutic use , Microsatellite Instability , Stomach Neoplasms , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Staging , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Treatment Outcome
11.
Arch Surg ; 146(9): 1086-92, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21576595

ABSTRACT

OBJECTIVE: To evaluate the comparative safety and efficacy of robotic vs laparoscopic gastrectomy for early-stage gastric cancer. DESIGN: Retrospective analysis. SETTING: Tertiary hospital. PATIENTS: Eight hundred twenty-seven patients with gastric cancer. INTERVENTIONS: Between July 2005 and April 2009, 827 patients with gastric cancer underwent 236 robotic and 591 laparoscopic radical gastrectomies with curative intent. The patients' data were prospectively collected and retrospectively analyzed. MAIN OUTCOME MEASURES: We performed a comparative analysis between the robotic surgery group and laparoscopic surgery group for preoperative patient characteristics, intraoperative factors, and postoperative morbidity and mortality. RESULTS: The robotic group was younger than the laparoscopic group, but other preoperative patient characteristics did not differ. The mean operative time for the robotic group (219.5 minutes) was on average 49 minutes longer than the laparoscopic group (170.7 minutes) (P < .001), while mean blood loss was significantly less in the robotic group (91.6 mL vs 147.9 mL; P = .002). The robotic group had mortality of 0.4% and morbidity of 11.0%, comparable with those of the laparoscopic group (P > .05). The number of lymph nodes retrieved per level was adequate in both groups and did not differ significantly. Robotic D1+α (n = 5), D1+ß (n = 126), and D2 (n = 105) dissections retrieved 27.2, 36.7, and 42.4 mean numbers of lymph nodes, respectively. Except for 3 cases in the laparoscopic group, all specimens had negative margins. CONCLUSIONS: Our largest comparative study demonstrates robotic gastrectomy to have better short-term and comparable oncologic outcomes compared with laparoscopic gastrectomy. A robotic approach to gastric cancer is a promising alternative to laparoscopic surgery.


Subject(s)
Gastrectomy/methods , Laparoscopy/methods , Robotics , Stomach Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Blood Loss, Surgical , Comorbidity , Female , Humans , Length of Stay , Lymph Node Excision , Male , Middle Aged , Quality of Life , Retrospective Studies , Stomach Neoplasms/epidemiology , Treatment Outcome
12.
Acad Radiol ; 17(8): 985-91, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20617548

ABSTRACT

RATIONALE AND OBJECTIVES: To characterize an iodized oil emulsion for computed tomography (CT) imaging of experimental hepatic tumors in rat models. MATERIALS AND METHODS: For characterizing the agents in normal rats, three rats were intravenously infused and imaged with clinical CT up to 1 week. Iopamidol solution was also used as controls (n = 3). For evaluating the feasibility of diagnosis of hepatic tumors, 12 rats were injected with C6 glial tumor cells into the liver 11, 9, 7, and 5 days before CT (n = 3 per day). After CT imaging, gross and histopathologic correlation of liver tumors with CT images were performed. RESULTS: CT numbers of aorta and inferior vena cava (IVC) increased immediately after injection of the emulsion and remained above 200 Hounsfield units for 1 hour (maximum: 295.67 +/- 27.65 in aorta and 347.07 +/- 10.58 in IVC). The mean attenuation in liver and spleen was relatively stable between 30 and 180 minutes (maximum: 188.84 +/- 18.70 in liver and 210.97 +/- 15.83 in spleen). All 20 tumors later confirmed by pathology were detected as hypodense lesions on CT (sensitivity: 100%; range, 2.0-16.4 mm). The mean enhancement ratios of liver at all time points were significantly higher than those of tumors (P < .05). CONCLUSION: The hepatic enhancement achieved by the iodized oil emulsion is reticuloendothelial system-specific with the property of blood pool enhancement and longer lasting than that achievable with the current water soluble agents. Thus, this agent may offer significant advantages for diagnosis of hepatic metastases.


Subject(s)
Contrast Media , Iodized Oil , Liver Neoplasms, Experimental/diagnostic imaging , Tomography, X-Ray Computed , Animals , Female , Liver/diagnostic imaging , Liver Neoplasms, Experimental/pathology , Rats , Rats, Sprague-Dawley , Spleen/diagnostic imaging , Vena Cava, Inferior/diagnostic imaging
13.
Pharm Res ; 27(7): 1408-15, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20424895

ABSTRACT

PURPOSE: The need for computed tomography (CT) of reticuloendothelial system (RES)-rich organs such as the liver is increasing, particularly in patients with suspected hepatic metastasis. CT images of the liver have been improved by encapsulating currently used, water-soluble iodine contrast agent in liposomes. The present study was performed to investigate a possibility to overcome the limitations of entrapped iodine in liposomes by preparing liposomes co-loaded with iopamidol, a water-soluble iodinated compound, and lipiodol, an iodized oil. METHODS: Iopamidol and lipiodol were simultaneously loaded in liposomes by modified reverse-phase evaporation method. The entrapped iodine concentration, mean particle size and polydispersity index of resulting liposomes were evaluated. Following intravenous injection of these liposomes into rats, CT scanning was performed. RESULTS: Simultaneous loading of iopamidol and lipiodol into liposomes resulted in entrapped iodine concentrations as high as 49.2 iodine mg/ml. The mean particle size was 280 nm, and the mean polydispersity index was 0.230. CT scanning with these iopamidol/lipiodol (I/L) liposomes into rats resulted in more pronounced and more persistent increases in RES-rich organs, liver and spleen, compared with free liposomes or liposomes loaded with iopamidol alone. CONCLUSIONS: These findings indicate that I/L liposomes have the potential to allow thorough CT examination of RES-rich organs.


Subject(s)
Contrast Media/pharmacology , Iodized Oil/pharmacology , Iopamidol/pharmacology , Liposomes/chemistry , Mononuclear Phagocyte System/drug effects , Tomography, X-Ray Computed/methods , Animals , Drug Delivery Systems , Female , Rats
14.
Invest Radiol ; 45(3): 142-8, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20065857

ABSTRACT

OBJECTIVES: To formulate an iodine-based contrast agent with an oil-in-water emulsion and to evaluate the feasibility of the agent for use as an interstitial computed tomographic (CT) lymphographic agent in a normal rat model. MATERIALS AND METHODS: The effect of iodized oil (lipiodol) content and the type of surfactant/cosurfactant on the resultant emulsion size and polydispersity was investigated to obtain an optimized lipiodol emulsion for CT lymphography. Optimized emulsions (144 mg/mL) were injected in the hind paws of 6 rats, using 0.5 mL per paw. As control groups, iopamidol solution and lipiodol diluted with squalene to adjust the injection volume with iodine concentration equivalent to the emulsions were used. Precontrast and postcontrast CT images up to 1 week after contrast agent injection were obtained. Time-enhancement curves of the popliteal lymph nodes were obtained. Analysis of variance and post hoc analysis with the Dunn procedure were used for comparing mean peak enhancement, time to peak enhancement, and sustained duration of contrast enhancement. RESULTS: Optimized emulsion formulations composed of 30% lipiodol and 282 mg/mL of 9:1 surfactant mixture (Tween 80:TPGS [alpha-tocopheryl polyethylene glycol succinate], Tween 80:Kollidon 12 PF, or Tween 80:Span 85) exhibited mean particle size less than 120 nm, and they were stable without significant particle size change up to 1 month. Targeted lymph nodes in all emulsion groups showed continuously increasing enhancement until 4 or 8 hours after injection, followed by continuous washout. Peak enhancement (time to peak enhancement) was 172.4 +/- 54.5 HU (Hounsfield unit) (384.0 +/- 131.5 minutes) for Tween 80:TPGS; 172.8 +/- 28.0 HU (432.0 +/- 107.3 minutes) for Tween 80:Kollidon 12 PF, and 177.2 +/- 68.9 HU (294.0 +/- 190.2 minutes) for Tween 80:Span 85. For iopamidol, peak enhancement of 153.0 +/- 46.1 HU (0.5 +/- 0.5 minutes) occurred early with rapid washout. For lipiodol as a reference agent, contrast enhancement continuously increased even 1 week after injection without washout (peak enhancement, 486.0 +/- 97.4 HU). Peak enhancement among the emulsion groups and the iopamidol group was not statistically different (P = 0.95). All emulsion groups showed more prolonged enhancement than the iopamidol group; enhancement duration for the emulsion groups was 534.0 +/- 481.1 minutes for Tween 80:TPGS; 957.0 +/- 524.8 minutes for Tween 80:Kollidon 12 PF; and 750.0 +/- 566.0 minutes for Tween 80:Span 85, and enhancement duration for iopamidol was 8.2 +/- 12.3 minutes (all P < 0.05 in multiple comparisons). However, there was no significant difference in enhancement duration among the 3 emulsion groups (P > 0.05). CONCLUSIONS: Iodized oil emulsion made with a surfactant mixture (Tween 80 as the main surfactant and TPGS, Kollidon 12 PF, or Span 85 as the cosurfactant) provided sufficient and sustained contrast enhancement on CT of targeted lymph nodes with washout on delayed phase.


Subject(s)
Contrast Media/chemistry , Iodized Oil/chemistry , Lymph Nodes/diagnostic imaging , Tomography, X-Ray Computed/methods , Analysis of Variance , Animals , Emulsions/chemistry , Feasibility Studies , Female , Rats , Rats, Sprague-Dawley
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