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1.  Collagen signaling enhances tumor progression after anti-VEGF therapy in a murine model of pancreatic ductal adenocarcinoma 
Cancer research  2013;74(4):1032-1044.
There is growing evidence that anti-angiogenic therapy stimulates cancer cell invasion and metastasis. However, the underlying molecular mechanisms responsible for these changes have not been fully defined. Here we report that anti-VEGF therapy promotes local invasion and metastasis by inducing collagen signaling in cancer cells. We show that chronic VEGF inhibition in a genetically engineered mouse model (GEMM) of pancreatic ductal adenocarcinoma (PDA) induces hypoxia, a less differentiated mesenchymal-like tumor cell phenotype, TGFβ expression, and collagen deposition and signaling. Additionally, we show that collagen signaling is critical for pro-tumorigenic activity of TGFβ in vitro. To further model the impact of collagen signaling in tumors, we evaluated PDA in mice lacking Sparc, a protein that reduces collagen binding to cell surface receptors. Importantly, we show that loss of Sparc increases collagen signaling and tumor progression. Together, these findings suggest that collagen actively promotes PDA spread and that enhanced disease progression associated with anti-VEGF therapy can arise from elevated ECM-mediated signaling.
PMCID: PMC3944405  PMID: 24346431
pancreatic cancer; VEGF; Sparc; collagen; Peak1; epithelial to mesenchymal transition
2.  Quantitative Measurement of Organic Acids in Tissues from Gastric Cancer Patients Indicates Increased Glucose Metabolism in Gastric Cancer 
PLoS ONE  2014;9(6):e98581.
The levels of organic acids representing metabolic pathway end products are important indicators of physiological status, and may be associated with metabolic changes in cancer. The aim of this study is to investigate the levels of organic acids in cancerous and normal tissues from gastric cancer patients and to confirm the role of metabolic alterations in gastric carcinogenesis. Organic acids in normal and cancerous tissues from forty-five patients with gastric adenocarcinoma were investigated by gas chromatography-mass spectrometry in selected ion monitoring mode as methoxime/tert-butyldimethylsilyl derivatives. We analysed the significant differences in the levels of organic acids in normal and cancer tissues and investigated the correlation of these levels in cancer tissues with clinicopathological features. The levels of Krebs cycle components, including α-ketoglutaric acid, succinic acid, fumaric acid, malic acid and oxaloacetic acid, were significantly increased in cancer tissues compared to normal tissues. In addition, the levels of glycolytic products, including pyruvic acid and lactic acid, as well as the levels of ketone bodies, including 3-hydroxybutyric acid, were also significantly increased in cancer tissues compared to normal tissues. The levels of ketone bodies in cancer tissues with differentiated histology and in intestinal-type cancer tissues were significantly increased. The organic acid profiling analysis described here may be a generally useful clinical tool for understanding the complexity of metabolic events in gastric adenocarcinoma, and organic acids may have potential as metabolic markers for the future discovery of diagnostic and therapeutic modalities.
PMCID: PMC4049586  PMID: 24911788
3.  Standardization of D2 lymphadenectomy and surgical quality control (KLASS-02-QC): a prospective, observational, multicenter study [NCT01283893] 
BMC Cancer  2014;14:209.
Extended systemic lymphadenectomy (D2) is standard procedure for surgical treatment of advanced gastric cancer (AGC) although less extensive lymphadenectomy (D1) can be applied to early gastric cancer. Complete D2 lymphadenectomy is the mandatory procedure for studies that evaluate surgical treatment results of AGC. However, the actual extent of D2 lymphadenectomy varies among surgeons because of a lacking consensus on the anatomical definition of each lymph node station. This study is aimed to develop a consensus for D2 lymphadenectomy and also to qualify surgeons that can perform both laparoscopic and open D2 gastrectomy.
This (KLASS-02-QC) is a prospective, observational, multicenter study to qualify the surgeons that will participate in the KLASS-02-RCT, which is a prospective, randomized, clinical trial comparing laparoscopic and open gastrectomy for AGC. Surgeons and reviewers participating in the study will be required to complete a questionnaire detailing their professional experience and specific gastrectomy surgical background/training, and the gastrectomy metrics of their primary hospitals. All surgeons must submit three laparoscopic and three open D2 gastrectomy videos, respectively. Each video will be allocated to five peer reviewers; thus each surgeon’s operations will be assessed by a total of 30 reviews. Based on blinded assessment of unedited videos by experts’ review, a separate review evaluation committee will decide whether or not the evaluated surgeon will participate in the KLASS-02-RCT. The primary outcome measure is each surgeon’s proficiency, as assessed by the reviewers based on evaluation criteria for completeness of D2 lymphadenectomy.
We believe that our study for standardization of D2 lymphadenectomy and surgical quality control (KLASS-02-QC) will guarantee successful implementation of the subsequent KLASS-02-RCT study. After making consensus on D2 lymphadenectomy, we developed evaluation criteria for completeness of D2 lymphadenectomy. We also developed a unique surgical standardization and quality control system that consists of recording unedited surgical videos, and expert review according to evaluation criteria for completeness of D2 lymphadenectomy. We hope our systematic approach will set a milestone in surgical standardization that is essential for surgical clinical trials. Additionally, our methods will serve as a novel system for educating surgeons and assessing surgical proficiency.
Trial registration
PMCID: PMC4000001  PMID: 24646327
Neoplasms of stomach; D2 lymphadenectomy; Gastrectomy; Laparoscopy; Standardization; Quality control
4.  Conventional Cytology Is Not Beneficial for Predicting Peritoneal Recurrence after Curative Surgery for Gastric Cancer: Results of a Prospective Clinical Study 
Journal of Gastric Cancer  2014;14(1):23-31.
The role of peritoneal washing cytology in determining further treatment strategies after surgery for gastric cancer remains unclear. One reason for this is the fact that optimal procedures to increase the accuracy of predicting peritoneal metastasis have not been established. The aim of this study was to evaluate the efficacy of cytology using samples harvested from two different abdominal cavity sites during gastric cancer surgery.
Materials and Methods
We prospectively recruited 108 patients who were clinically diagnosed with locally advanced gastric cancer (higher than cT1 stage disease). Peritoneal washing fluids were collected from the pouch of Douglas and the subphrenic area. Patients were prospectively followed up for 2 years to determine the recurrence and survival rates.
Thirty-three patients dropped out of the study for various reasons, so 75 patients were included in the final analysis. Seven patients (9.3%) showed positive cytology findings, of whom, three showed peritoneal recurrence. Tumor size was the only factor associated with positive cytology findings (P=0.037). The accuracy and specificity of cytology for predicting peritoneal recurrence were 90.1% and 94.2%, respectively, whereas the sensitivity was 50.0%. The survival rate did not differ between patients with positive cytology findings and those with negative cytology findings (P=0.081).
Peritoneal washing cytology using samples harvested from two different sites in the abdominal cavity was not able to predict peritoneal recurrence or survival in gastric cancer patients. Further studies will be required to determine whether peritoneal washing cytology during gastric cancer surgery is a meaningful procedure.
PMCID: PMC3996246  PMID: 24765534
Stomach neoplasms; Cytology; Peritoneum; Recurrence
5.  Outcomes of Critical Pathway in Laparoscopic and Open Surgical Treatments for Gastric Cancer Patients: Patients Selection for Fast-Track Program through Retrospective Analysis 
Journal of Gastric Cancer  2013;13(2):98-105.
The aim of this study is to investigate the clinical factors affecting on the cure rate by invasive and open surgery for gastric cancer and to establish a subgroup of patients who can be applied by the early recovery after surgery program through this retrospective analysis.
Materials and Methods
In this retrospective study, we analyzed 425 patients who underwent gastric cancer surgery between January 2011 and December 2011 and were managed with conventional clinical therapies. This clinical algorithm was made when the patient was in minimally invasive surgery group and discharged from hospital one day faster than them in open surgery group.
The completion rate of the clinical pathway was 62.4%. Despite the different applications of clinical pathway, completion rate in minimally invasive surgery group was significantly higher than that of open group (P<0.001). In multivariate analysis, the surgical procedure of minimally invasive surgery (odds ratio=4.281) was the most predictable factor to complete clinical pathway. Additionally, younger patients (odds ratio=1.933) who underwent distal gastrectomy (odds ratio=1.999) without combined resection (odds ratio=3.069) were predicted to accomplish the clinical pathway without any modifications.
We concluded that high efficacy of the clinical pathway for gastric cancer surgery was expected to selected patients through retrospective analysis (expected completion rate=85.4%). In addition, these patients would become enrolled criteria for early recovery program in gastric cancer surgery.
PMCID: PMC3705139  PMID: 23844324
Stomach neoplasms; Critical pathways; Gastrectomy; Minimally invasive
6.  Totally Laparoscopic Surgery for Gastric Cancer 
Journal of Gastric Cancer  2013;13(1):1-2.
PMCID: PMC3627801  PMID: 23610713
7.  Comparison of Intracorporeal Reconstruction after Laparoscopic Distal Gastrectomy with Extracorporeal Reconstruction in the View of Learning Curve 
Journal of Gastric Cancer  2013;13(1):34-43.
The intracorporeal reconstruction after laparoscopic gastrectomy can minimize postoperative pain, and give better cosmetic effect, while it may have technical difficulties and require the learning curve. This study aimed to analyze the surgical outcome of intracorporeal reconstruction according to the surgeon's experience comparing with extracorporeal procedure.
Materials and Methods
From January 2009 to September 2011, intracorporeal reconstruction in laparoscopic surgery for gastric cancer was performed for 71 patients (Intra group). During same period, 231 patients underwent laparoscopy-assisted gastrectomy (Extra group). These patients were classified into initial (1st to 20th case of intra group), intermediate (21th to 46th case), and experienced (after 47th case) phases.
Intracorporeal procedures included 35 cases of Billroth-I, 30 Billroth-II and 6 Roux en Y reconstructions. In the initial phase, operation time (P=0.022) were significantly longer for the patients of intra group than them of extra group. Although the difference was not significant, the length of hospital stay was longer and complication rate was higher in the intra group. In intermediate and experienced phases, there was no difference between two groups in operation time and hospital stay. In these phases, complication rate was lower in the intra group than the extra group (3.9% versus 9.7%). The pain scale was significantly lower post operation day 5 in the intra group.
Intracorporeal reconstruction after laparoscopic distal gastrectomy was feasible and safe, and the technique was stabilized after 20th case if the surgeon has sufficient experiences when we compared it with extracorporeal reconstruction.
PMCID: PMC3627805  PMID: 23610717
Intracorporeal; Extracorporeal; Billorth I; Billroth II; Roux en Y
8.  Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target 
In contrast to mitochondria in healthy cells, which utilize oxidative phosphorylation, malignant cells undergo elevated glycolysis for energy production using glucose. The objectives of this study were to evaluate whether the expression of various molecules, including pyruvate dehydrogenase kinase-1 (PDK-1), is involved in the altered glucose metabolism associated with gastric cancer prognosis and to assess the role of a therapeutic agent in targeting glucose metabolism in gastric cancer. Immunohistochemistry was performed on gastric cancer tissues obtained from 152 patients who underwent curative resection to assess the expression of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), hexokinase-2 (HK-2) and PDK-1. In an in vitro analysis, the lactate production and glucose uptake levels, cellular viability and 5-fluorouracil (5-FU) responses were evaluated before and after treatment with dichloroacetate (DCA), a PDK-1 inhibitor, in the MKN45 and AGS gastric cancer cell lines and in the non-cancerous HEK293 cell line. GLUT-1 and PDK-1 expression was significantly associated with tumor progression, although only PDK-1 expression was an independent prognostic factor for patients who received 5-FU adjuvant treatment. There was no significant difference in cell viability between the HEK293 and gastric cancer cell lines following DCA treatment. However, DCA treatment reduced lactate production and increased responsiveness to 5-FU in MKN45 cells, which expressed high levels of PDK-1 in comparison to the other cell lines. Thus, PDK-1 may serve as a biomarker of poor prognosis in patients with gastric cancer. In addition, PDK-1 inhibitors such as DCA may be considered an additional treatment option for patients with PDK-1-expressing gastric cancers.
PMCID: PMC3583751  PMID: 23135628
gastric neoplasm; chemotherapy; pyruvate dehydrogenase; prognosis
9.  The Effects of Helicobacter pylori on the prognosis of patients with curatively resected gastric cancers in a population with high infection rate 
The goal of this study was to assess the correlation between the Helicobacter pylori status of patients who underwent curative resection for gastric adenocarcinoma and their prognosis in Eastern societies where H. pylori infection is prevalent.
Between 2006 and 2007, 192 patients who had a curative resection for the treatment of gastric adenocarcinoma were enrolled in the study. Of these patients, 18 were excluded due to an inexact evaluation of the H. pylori status, thereby leaving 174 patients in the final analysis. Serologic testing for H. pylori was assessed using an enzyme-linked immunosorbent assay kit for immunoglobulin G, and the histological presence of H. pylori was identified using the Giemsa stain.
Of the 174 patients, 111 patients (63.8%) were confirmed for H. pylori infection. H. pylori status did not correlate with the overall or disease-free survival. For patients with stage III or IV gastric cancer, a positive H. pylori status was a significant predictive factor for recurrence over that of a negative H. pylori status (P = 0.019). Negative H. pylori status was a predictive factor for recurrence in multivariable analysis (relative risk, 2.724; 95 confidence interval, 1.192 to 6.228).
Helicobacter pylori status did not correlate with the clinicopathologic factors of gastric adenocarcinoma. However, a negative Helicobacter pylori status may be a predictive factor for recurrence in patients diagnosed with advanced gastric adenocarcinoma.
PMCID: PMC3467386  PMID: 23091792
Helicobacter pylori; Stomach neoplasm; Prognosis; Survival
10.  Present Condition Analysis of Physician Assistant in Korea 
Journal of Korean Medical Science  2012;27(9):981-986.
This study intended to identify the need for the legalization and development of a systematic program for physician assistants (PAs) by understanding the actual state of PA operation in hospitals. In 114 hospitals assigned as resident training hospitals for surgery, a survey was conducted on the personnel working as PAs in those hospitals; the survey included general personal information, working conditions, training time, and satisfaction. A total of 192 PAs in surgery at 35 hospitals responded to the survey. The types of PAs are Surgical Assistant, Clinical Physician Assistant, Wound Ostomy Care Nurse, Coordinator, and Clinical Research Coordinator. Types of work PAs preformed are surgical assistance, wound dressing, educating patients, overlooking consultation, doing paper works, writing operation records, and confirming examination results which were ordered. The satisfaction level for the position which PAs hold were 29.1% and and satisfaction level which doctors see towards PA was 15%. The role and the job descriptions of PAs are not clear cut, there are many discrepancies among hospitals we studied. As a result, legalization and the implementation of standardized role of PAs will lead to increase level of satisfactions in the work force and the quality of work which PAs perform will be greater.
PMCID: PMC3429838  PMID: 22969241
Physician Assistants; General Surgery
11.  Comparison of Surgical Outcomes between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: The Learning Curve of Robotic Surgery 
Journal of Gastric Cancer  2012;12(3):156-163.
Laparoscopic gastrectomy is a widely accepted surgical technique. Recently, robotic gastrectomy has been developed, as an alternative minimally invasive surgical technique. This study aimed to evaluate the question of whether robotic gastrectomy is feasible and safe for the treatment of gastric cancer, due to its learning curve.
Materials and Methods
We retrospectively reviewed the prospectively collected data of 100 consecutive robotic gastrectomy patients, from November 2008 to March 2011, and compared them to 282 conventional laparoscopy patients during the same period. The robotic gastrectomy patients were divided into 20 initial cases; and all subsequent cases; and we compared the clinicopathological features, operating times, and surgical outcomes between the three groups.
The initial 20 robotic gastrectomy cases were defined as the initial group, due to the learning curve. The initial group had a longer average operating time (242.25±74.54 minutes vs. 192.56±39.56 minutes, P>0.001), and hospital stay (14.40±24.93 days vs. 8.66±5.39 days, P=0.001) than the experienced group. The length of hospital stay was no different between the experienced group, and the laproscopic gastrectomy group (8.66±5.39 days vs. 8.11±4.10 days, P=0.001). The average blood loss was significantly less for the robotic gastrectomy groups, than for the laparoscopic gastrectomy group (93.25±84.59 ml vs. 173.45±145.19 ml, P<0.001), but the complication rates were no different.
Our study shows that robotic gastrectomy is a safe and feasible procedure, especially after the 20 initial cases, and provides a satisfactory postoperative outcome.
PMCID: PMC3473222  PMID: 23094227
Robotic; Laparoscopy; Compared; Gastrectomy; Learning curve
12.  Clinicopathologic Significance of Gastric Adenocarcinoma with Neuroendocrine Features 
Journal of Gastric Cancer  2011;11(4):195-199.
Composite neuroendocrine-exocrine carcinomas are malignancies that have two distinct components residing within the same tumor: an adenocarcinomatous portion and a neuroendocrine portion. This is rare in gastric cancers; however, poorly differentiated adenocarcinomas can sometimes reveal evidence of neuroendocrine features (NEF) or be 'mixed endocrine and exocrine carcinomas'. This study aimed to review NEF in gastric adenocarcinoma and to evaluate its prognostic significance.
Materials and Methods
We selected 29 patients who were diagnosed with gastric adenocarcinoma with NEF and received gastrectomies at the Department of Surgery, Ajou University Hospital between January 2001 and December 2009. We analyzed the clinicopathologic features of gastric cancer with NEF and the prognosis associated with such tumors.
The pathologic result with respect to TNM staging of the gastric cancers with NEF were as follows: 5 cases of T1, 5 cases of T2, 10 cases of T3, and 9 cases of T4. There were 7 cases of N0, 7 cases of N1, 8 cases of N2 and 7 cases of N3. The staging of patients with NEF was higher than that of patients without NEF. Especially tumor lymphovascular invasion rate was 82.8%. The overall survival of patients with gastric cancer characterized by NEF was 73.8 months.
Positive NEF status might be correlated with clinicopathologic parameters such as a high stage and high frequency of regional lymph node metastasis.
PMCID: PMC3273688  PMID: 22324009
Stomach neoplasms; Adenocarcinoma; Neuroendocine tumors
13.  Efficacy of Roux-en-Y Reconstruction Using Two Circular Staplers after Subtotal Gastrectomy: Results from a Pilot Study Comparing with Billroth-I Reconstruction 
Journal of Gastric Cancer  2011;11(4):219-224.
The Roux en Y method has rarely been performed due to longer operation time and high risk of complication, despite several merits including prevention of bile reflux. We conducted a retrospective review of the result of Roux en Y reconstruction using two circular staplers after subtotal gastrectomy.
Materials and Methods
From December 2008 to May 2009, a total of 26 patients underwent Roux en Y reconstruction using two circular staplers after subtotal gastrectomy, and seventy-two patients underwent Billroth-I reconstruction. Roux en Y anastomosis was performed using two circular staplers without hand sewing anastomosis. We compared clinicopathologic features and surgical outcomes between the two groups. All patients underwent gastrofiberscopy between six and twelve months after surgery to compare the bile reflux.
No significant differences in clinicopathologic findings were observed between the two groups, except for the rate of minimal invasive surgery (P=0.004) and cancer stage (P=0.002). No differences in the rate of morbidity (P=0.353) and admission duration (P=0.391) were observed between the two groups. Gastrofiberscopic findings showed a significant reduction of bile reflux in the remnant stomach in the Roux en Y group (P=0.019).
When compared with Billroth-I reconstruction, Roux en Y reconstruction using the double stapler technique was found to reduce bile reflux in the remnant stomach without increasing postoperative morbidity. Based on these results, we planned to begin a randomized controlled clinical trial for comparison of Roux en Y reconstruction using this method with Billroth-I anastomosis.
PMCID: PMC3273692  PMID: 22324013
Stomach neoplasms; Gastrectomy; Reconstructive surgical procedure
14.  Giant Mesenteric Cystic Lymphangioma Originating from the Lesser Omentum in the Abdominal Cavity 
Journal of Gastric Cancer  2011;11(4):243-247.
A 48 year old woman was diagnosed with a huge cystic mass in her abdominal cavity. She complained of significant abdominal discomfort due to the mass. The abdominal computed tomography revealed a giant multi-lobulated mass, measuring 26×12 cm in size, adjacent to the lesser curvature of the stomach. In the operation field, the mass was found to originate from the lesser omentum, including the right and left gastric vessels and the vagus nerves, and to invade the lesser curvature of the stomach. For curative resection, distal subtotal gastrectomy with mass excision followed by gastroduodenostomy were performed. This mass was pathologically diagnosed to be a mesenteric cystic lymphangioma; in fact, the largest ever reported. The patient had no complications during the postoperative period and was discharged from the hospital on the seventh day after surgery.
PMCID: PMC3273697  PMID: 22324018
Lymphangioma; Gastrectomy; Omentum
15.  Robotic redo fundoplication for incompetent wrapping after antireflux surgery: A case report 
Incidence of gastroesophageal reflux disease (GERD) is high. antireflux surgery with specific indications could be an option. Nissen fundoplication is the most popular surgical procedure for GERD, and recent results using laparoscopy have reported excellent short- and mid-term results. Regarding surgical outcome of antireflux surgery, the rate of complications has been reported as below 2.4%, but rare cases still require reoperation.
A 53-year old male patient underwent laparoscopic Nissen fundoplication three years ago owing to gastroesophageal reflux disease (GERD) troubled by dysphagia and heartburn However, despite undergoing surgery, his symptoms did not show improvement .A robotic redo fundoplication was planned. The patient recovered uneventfully, and the esophagography on postoperative day four revealed improvement of previous upward contrast reflux and distension of the distal esophagus during swallowing had disappeared. Dysphagia and heartburn had still not occurred at one year follow-up.
Redo antireflux surgery for postoperative stricture is not an easy procedure due to postoperative adhesion and anatomical change. Robotic surgery may be more helpful for precise dissection of the adhesion site by a previous operation and robotic suturing for re-fundoplication was more effective.
Re-do fundoplication using a robot, which is a complicated procedure compared with primary anti-reflux surgery would be a general procedure in the near future.
PMCID: PMC3215201  PMID: 22096753
Gastroesophageal reflux disease; Redo fundoplication; Robotic surgery
16.  Efficacy of Endoscopic Ultrasonography for Prediction of Tumor Depth in Gastric Cancer 
Journal of Gastric Cancer  2011;11(2):109-115.
As the proportion of early gastric cancer (EGC) has recently been increased, minimally invasive treatment is currently accepted as main therapy for EGC. Accurate preoperative staging is very important in determining treatment options. To know the accuracy of endoscopic ultrasonography (EUS), we compared the depth of invasion of the tumor with preoperative EUS and postoperative pathologic findings.
Materials and Methods
We retrospectively analyzed 152 patients who underwent EUS before laparoscopic gastrectomy. The preoperative EUS results were compared with the pathological findings.
The overall proportion of coincidence for depth of invasion between EUS and pathologic results was 41.4%. Univariate analysis showed that the rate of corrected prediction of EUS for tumor depth significantly decreased for the lesions more than 3cm in diameter (P=0.033), and those with a depressed morphology (P=0.035). In multivariate analysis, the depressed type (P=0.029, OR=2.873) and upper lesion (P=0.035, OR=2.151) was the significantly independent factors influencing the inaccurate prediction of EUS for tumor depth.
When we decide the treatment modality considering the clinical depth of invasion by EUS, the possibility of discordance with pathologic results should be considered for the lesions located in the upper third of the stomach and with a depressed morphology.
PMCID: PMC3204484  PMID: 22076211
Stomach neoplasms; Endosonography; Neoplasm invasiveness
17.  Operative Risk Factors in Gastric Cancer Surgery for Elderly Patients 
Journal of Gastric Cancer  2011;11(2):116-121.
Gastric cancer surgery is a common operation in East Asia, such as Korea and Japan, and there has been a significant increase in the need for this procedure due to the aging population. As a result, surgery for the treatment of gastric cancer for elderly patients is expected to increase. This study examined the effect of old age on gastric cancer surgery, and analyzed the operative risk factors for elderly patients.
Materials and Methods
From November 2008 to August 2010, 590 patients, who underwent a curative resection for gastric cancers, were enrolled. Patients who underwent palliative or emergency surgery were excluded. A retrospective analysis of the correlation between surgical outcomes and age was performed. The elderly were defined as patients who were over the age of 65 years.
The mean age of all patients was 58.3 years, and complications occurred in 87 cases (14.7%). The most common complication was wound infection and severe complications requiring surgical, endoscopic, or radiologic intervention developed in 52 cases (8.8%). The rate of complications increased with increasing age of the patients. Univariate analysis revealed age, comorbidity, extent of resection, operation time, and combined resection to be associated with surgical complications. In particular, age over 75 years old, operation time, and comorbidity were predictive factors in multivariate analysis. In the elderly, only comorbidity was associated with surgical complications.
The patients' age is the most important factor for predicting surgical complications. Surgeons should pay an attention to the performance of gastric cancer surgery on elderly patients. In particular, it must be performed carefully for elderly patients with a comorbidity.
PMCID: PMC3204490  PMID: 22076212
Stomach neoplasms; Risk factors; Gastrectomy; Aged
18.  The efficacy of preoperative PET/CT for prediction of curability in surgery for locally advanced gastric carcinoma 
The benefits of preoperative 18FDG-PET/CT for gastric cancer remain uncertain. The aim of this study was to investigate the effects of preoperative 18FDG-PET/CT on the surgical strategy for locally advanced gastric cancer retrospectively.
From January 2007 to November 2008, 18FDG-PET/CT was performed in 142 patients who had been diagnosed with advanced gastric cancer by computed tomography or gastrofiberscope findings.
Detection rates were 88.7% (126/142) for primary tumors and 24.6% (35/142) for local lymph nodes (LN). Nine patients with metastatic lesions underwent induction chemotherapy without operation. Of 133 patients subjected to operation, positive FDG uptake in primary tumors (p = 0.047) and local lymph nodes (p < 0.001) was related to non-curable operations. The mean standard uptake value (SUV) of primary tumors of patients who underwent non-curable operations was significantly higher than that of patients with curable operations (p = 0.001). When the SUV was greater than 5 and FDG uptake of LN was positive, non-curable operations were predicted with a sensitivity of 35.2%, a specificity of 91.0% and an accuracy of 76.7%.
High SUV of the primary tumor and positive FDG uptake in local lymph nodes at PET/CT could predict non-curative resection in locally advanced gastric cancer. Therefore, information from preoperative PET/CT can help physician decisions regarding other modalities without laparotomy.
PMCID: PMC2964718  PMID: 20932345
19.  Outcomes of Modified FOLFOX-6 as First Line Treatment in Patients with Advanced Gastric Cancer in a Single Institution; Retrospective Analysis 
Treatment options for patients with advanced gastric cancer remain limited. Few studies have investigated the efficacy and tolerability of the combination regimen of oxaliplatin and 5-fluorouracil with leucovorin for patients with advanced gastric cancer. The goal of this study was to examine the efficacy and toxicity of a modified FOLFOX-6 (mFOLFOX-6) regimen as a first-line chemotherapy regimen for patients with advanced gastric cancer.
Materials and Methods
From March, 2006, to December, 2007, 82 patients with advanced gastric cancer received 100 mg/m2 oxaliplatin and 100 mg/m2 leucovorin on the first day of treatment, followed by 2,400 mg/m2 of 5-fluorouracil on the first and second days of treatment every 2 weeks as a first-line treatment.
The median age of the enrolled patients was 62 years (range; 30~75). Out of 82 patients, 34 cases (41.5%) were recurrent cases after curative resection, and the other 48 cases were unresectable or non-curative resectable cases. Their response was evaluated every 6 weeks. The overall response rate was 40.2%, with 2 (2.4%) complete response and 31 (37.8%) partial responses. The median time to progression (TTP) and overall survival (OS) time were 6.0 months (95% confidence interval [CI]: 4.69~7.31) and 13.0 months (7.99~18.0), respectively. The grade 3~4 hematologic toxicities observed included neutropenia (34.1%), thrombocytopenia (7.3%), and anemia (1.2%). The gastrointestinal toxicities observed included grade 3~4 nausea (9.8%) and vomiting (7.3%). Six patients (7.3%) experienced grade 3 neuropathy. No treatment-related deaths were recorded.
The modified FOLFOX-6 regimen is effective and well tolerated as a first-line chemotherapy regimen for patients with advanced gastric cancer.
PMCID: PMC2848749  PMID: 20369047
Stomach neoplasms; Adjuvant chemotherapy; Oxaliplatin; FOLFOX regimen
20.  Perforation of the colon by invading recurrent gastrointestinal stromal tumors during sunitinib treatment 
The molecular targets of sunitinib are receptor tyrosine kinases (RTKs), and this drug has also been known to exert blocking effects on the activation of KIT, which is similar to the mechanism of action of imatinib. Moreover, sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation. We report here a 70-year-old patient diagnosed with a recurrent gastrointestinal stromal tumor (GIST), which invaded the transverse colon and led to a perforation during sunitinib treatment. A computed tomography scan and 3-dimensional reconstruction showed necrosis of the recurrent hepatic mass and perforation of the invaded transverse colon. After percutaneous drainage of the intraperitoneal abscess, antibiotic treatment and restricted diet, the condition of the patient improved. The present case is the first to report that sunitinib, which is administered to treat GIST resistant to imatinib, can cause unexpected colon perforation and subsequent peritonitis.
PMCID: PMC2760196  PMID: 18932293
Gastrointestinal stromal tumors; Recurrence; Sunitinib; Intestinal perforation

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