Woo Jin Hyung

Morbidity and mortality of laparoscopic gastrectomy versus open gastrectomy for gastric cancer: an interim report--a phase III multicenter, prospective, randomized Trial (KLASS Trial).

Objective:The aim of this study was to evaluate the safety of this trial with respect to morbidity and mortality. Summary Background Data:Laparoscopic-assisted distal gastrectomy (LADG) is rapidly gaining popularity. However, there is limited evidence regarding its oncologic safety. We therefore conducted a phase III multicenter, prospective, randomized study comparing LADG with open gastrectomy (ODG). Methods:Patient eligibility criteria were pathologically-proven adenocarcinoma, 20 to 80 years of age, preoperative stage I, no history of other cancer, chemotherapy, or radiotherapy. The primary end point was to determine whether there is a difference in overall survival between 2 groups. The morbidity and mortality were compared to evaluate the safety of this trial. The time was decided on the hypothesis that the morbidity of this trial was not significantly different from that of previous reports on open gastric cancer surgeries (17%–20%). This study is registered at ClinicalTrials.gov and carries the following ID number: NCT00452751. Results:A total of 342 patients were randomized (LADG, 179 patients; ODG, 161 patients) between January 1, 2006 and July 19, 2007. There were no significant differences between the 2 groups in age, gender, and comorbidities. The postoperative complication rates of the LADG and ODG groups were 10.5% (17/179) and 14.7% (24/163), respectively (P = 0.137). Reoperations were required in 3 cases each group. The postoperative mortality was 1.1% (2/179) and 0% (0/163) in the LADG and ODG groups (P = 0.497), respectively. Conclusion:There was no significance difference in the morbidity and mortality between the 2 groups. Therefore, we conclude that this trial is safe and is thus ongoing.

Robot-assisted gastrectomy with lymph node dissection for gastric cancer: lessons learned from an initial 100 consecutive procedures.

Objective:To evaluate the technical feasibility, effectiveness, and safety of robot-assisted gastrectomy (RAG) with lymphadenectomy, using the da Vinci system through analyses of our initial series of 100 consecutive patients. Summary Background Data:The application of robotic surgery was proven to be one of the best cutting-edge technologies for successful minimally invasive surgery by providing solutions to the many drawbacks of laparoscopic surgery, yet few reports have studied robotic surgery in gastric cancer. Methods:A review of a prospectively designed database at our institute from July 2005 to October 2007 revealed a series of 100 consecutive RAG patients with a preoperative diagnosis of early gastric cancer. Clinicopathologic characteristics and surgical outcomes were analyzed. Results:All operations were performed successfully without open or laparoscopic conversion. There were 33 total gastrectomies and 67 subtotal gastrectomies with D1+&bgr; or extended lymphadenectomy (D2). The mean total operation time and console time were 231 and 150 minutes, respectively. There were 13 postoperative morbidities and 1 postoperative mortality. The first flatus was noted on postoperative day 2.9, soft diet was started on postoperative day 4.2, and the mean postoperative hospital stay was 7.8 days. Although all patients were diagnosed as early gastric cancer preoperatively, the final pathology report revealed that 19 patients exhibited a depth deeper than T2. The mean number of retrieved lymph nodes was 36.7 (range, 11–83). None of the specimens showed microscopic tumor involvement in the resection line. Conclusions:This study demonstrated that RAG with lymphadenectomy can be applied safely and effectively for patients with gastric cancer.

Long-Term Results of Laparoscopic Gastrectomy for Gastric Cancer: A Large-Scale Case-Control and Case-Matched Korean Multicenter Study

PURPOSE The oncologic outcomes of laparoscopy-assisted gastrectomy for the treatment of gastric cancer have not been evaluated. The aim of this study is to validate the efficacy and safety of laparoscopic gastrectomy for gastric cancer in terms of long-term survival, morbidity, and mortality retrospectively. PATIENTS AND METHODS The study group comprised 2,976 patients who were treated with curative intent either by laparoscopic gastrectomy (1,477 patients) or open gastrectomy (1,499 patients) between April 1998 and December 2005. The long-term 5-year actual survival analysis in case-control and case-matched population was conducted using the Kaplan-Meier method. The morbidity and mortality and learning curves were evaluated. RESULTS In the case-control study, the overall survival, disease-specific survival, and recurrence-free survival (median follow-up period, 70.8 months) were not statistically different at each cancer stage with the exception of an increased overall survival rate for patients with stage IA cancer treated via laparoscopy (laparoscopic group; 95.3%, open group: 90.3%; P < .001). After matching using a propensity scoring system, the overall survival, disease-specific survival, and recurrence-free survival rates were not statistically different at each stage. The morbidity of the case-matched group was 15.1% in the open group and 12.5% in the laparoscopic group, which also had no statistical significance (P = .184). The mortality rate was also not statistically significant (0.3% in the open group and 0.5% in the laparoscopic group; P = 1.000). The mean learning curve was 42. CONCLUSION The long-term oncologic outcomes of laparoscopic gastrectomy for patients with gastric cancer were comparable to those of open gastrectomy in a large-scale, multicenter, retrospective clinical study.

The impact of comorbidity on surgical outcomes in laparoscopy-assisted distal gastrectomy: a retrospective analysis of multicenter results.

Objective:The purpose of this study was to evaluate the impact of comorbidities on the surgical outcomes in laparoscopy-assisted distal gastrectomy (LADG). Summary Background Data:Although laparoscopic gastrectomy is less invasive than conventional open surgery, surgeons are still concerned with surgical outcomes associated with comorbidity. Methods:We retrospectively collected data on 1324 patients who underwent LADG between April 1998 and December 2005 by 10 surgeons in 10 hospitals. After excluding 87 patients who had an unusual medical history or surgical methods, 1237 patients were enrolled for analysis to evaluate the effect of comorbidities on the surgical outcomes. Results:Seven patients (0.6%) died during their hospitalization, and postoperative complications occurred in 162 (13.1%) of 1237 patients. According to univariate analysis, gender, number of comorbidities, reconstruction type, and the surgeons experience in laparoscopy-assisted gastrectomy (LAG) were related to postoperative local complications; age and comorbidity were related to systemic complications; and comorbidity was the only variable related to hospital mortality. Comorbidity was a predictive risk factor for local complications (odds ratio (OR): 1.79) and systemic complications (OR: 2.89) in multivariate analysis. The patients with pulmonary comorbidity were related to most types of immediate postoperative complications compared with other comorbidities. Conclusions:Our study suggests that comorbidities of patients could be a predictive risk factor for surgical complication after LADG. Therefore, patients with early gastric cancer having comorbidity should be considered for one of the limited surgeries. In addition, surgeons should carefully assess patients with comorbidities with full perioperative attention.

Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01)

OBJECTIVE To determine the safety of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG) in patients with clinical stage I gastric cancer in Korea. BACKGROUND There is still a lack of large-scale, multicenter randomized trials regarding the safety of LADG. METHODS A large-scale, phase 3, multicenter, prospective randomized controlled trial was conducted. The primary end point was 5-year overall survival. Morbidity within 30 postoperative days and surgical mortality were compared to evaluate the safety of LADG as a secondary end point RESULTS : A total of 1416 patients were randomly assigned to the LADG group (n = 705) or the ODG group (n = 711) between February 1, 2006, and August 31, 2010, and 1384 patients were analyzed for modified intention-to-treat analysis (ITT) and 1256 were eligible for per protocol (PP) analysis (644 and 612, respectively). In the PP analysis, 6 patients (0.9%) needed open conversion in the LADG group. The overall complication rate was significantly lower in the LADG group (LADG vs ODG; 13.0% vs 19.9%, P = 0.001). In detail, the wound complication rate of the LADG group was significantly lower than that of the ODG group (3.1% vs 7.7%, P < 0.001). The major intra-abdominal complication (7.6% vs 10.3%, P = 0.095) and mortality rates (0.6% vs 0.3%, P = 0.687) were similar between the 2 groups. Modified ITT analysis showed similar results with PP analysis. CONCLUSIONS LADG for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complication compared with conventional ODG.

Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial

BACKGROUND Chemotherapy is the standard of care for incurable advanced gastric cancer. Whether the addition of gastrectomy to chemotherapy improves survival for patients with advanced gastric cancer with a single non-curable factor remains controversial. We aimed to investigate the superiority of gastrectomy followed by chemotherapy versus chemotherapy alone with respect to overall survival in these patients. METHODS We did an open-label, randomised, phase 3 trial at 44 centres or hospitals in Japan, South Korea, and Singapore. Patients aged 20-75 years with advanced gastric cancer with a single non-curable factor confined to either the liver (H1), peritoneum (P1), or para-aortic lymph nodes (16a1/b2) were randomly assigned (1:1) in each country to chemotherapy alone or gastrectomy followed by chemotherapy by a minimisation method with biased-coin assignment to balance the groups according to institution, clinical nodal status, and non-curable factor. Patients, treating physicians, and individuals who assessed outcomes and analysed data were not masked to treatment assignment. Chemotherapy consisted of oral S-1 80 mg/m(2) per day on days 1-21 and cisplatin 60 mg/m(2) on day 8 of every 5-week cycle. Gastrectomy was restricted to D1 lymphadenectomy without any resection of metastatic lesions. The primary endpoint was overall survival, analysed by intention to treat. This study is registered with UMIN-CTR, number UMIN000001012. FINDINGS Between Feb 4, 2008, and Sept 17, 2013, 175 patients were randomly assigned to chemotherapy alone (86 patients) or gastrectomy followed by chemotherapy (89 patients). After the first interim analysis on Sept 14, 2013, the predictive probability of overall survival being significantly higher in the gastrectomy plus chemotherapy group than in the chemotherapy alone group at the final analysis was only 13·2%, so the study was closed on the basis of futility. Overall survival at 2 years for all randomly assigned patients was 31·7% (95% CI 21·7-42·2) for patients assigned to chemotherapy alone compared with 25·1% (16·2-34·9) for those assigned to gastrectomy plus chemotherapy. Median overall survival was 16·6 months (95% CI 13·7-19·8) for patients assigned to chemotherapy alone and 14·3 months (11·8-16·3) for those assigned to gastrectomy plus chemotherapy (hazard ratio 1·09, 95% CI 0·78-1·52; one-sided p=0·70). The incidence of the following grade 3 or 4 chemotherapy-associated adverse events was higher in patients assigned to gastrectomy plus chemotherapy than in those assigned to chemotherapy alone: leucopenia (14 patients [18%] vs two [3%]), anorexia (22 [29%] vs nine [12%]), nausea (11 [15%] vs four [5%]), and hyponatraemia (seven [9%] vs four [5%]). One treatment-related death occurred in a patient assigned to chemotherapy alone (sudden cardiopulmonary arrest of unknown cause during the second cycle of chemotherapy) and one occurred in a patient assigned to chemotherapy plus gastrectomy (rapid growth of peritoneal metastasis after discharge 12 days after surgery). INTERPRETATION Since gastrectomy followed by chemotherapy did not show any survival benefit compared with chemotherapy alone in advanced gastric cancer with a single non-curable factor, gastrectomy cannot be justified for treatment of patients with these tumours. FUNDING The Ministry of Health, Labour and Welfare of Japan and the Korean Gastric Cancer Association.

Correlation of KIT and platelet-derived growth factor receptor |[alpha]| mutations with gene activation and expression profiles in gastrointestinal stromal tumors

Activating mutations of KIT and platelet-derived growth factor receptor α (PDGFRA) are known to be alternative and mutually exclusive genetic events in the development of gastrointestinal stromal tumors (GISTs). We examined the effect of the mutations of these two genes on the gene expression profile of 22 GISTs using the oligonucleotide microarray. Mutations of KIT and PDGFRA were found in 17 cases and three cases, respectively. The remaining two cases had no detectable mutations in either gene. The mutation status of KIT and PDGFRA was directly related to the expression levels of activated KIT and PDGFRA, and was also related to the different expression levels of activated proteins that play key roles in the downstream of the receptor tyrosine kinase III family. To evaluate the impact of mutation status and the importance of the type of mutation in gene expression and clinical features, microarray-derived data from 22 GISTs were interpreted using a principal component analysis (PCA). Three relevant principal component representing mutation of KIT, PDGFRA and chromosome 14q deletion were identified from the interpretation of the oligonucleotide microarray data with PCA. After supervised analysis, there was at least a two fold difference in expression between GISTs with KIT and PDGFRA mutation in 70 genes. Our findings demonstrate that mutations of KIT and PDGFRA affect differential activation and expression of some genes, and can be used for the molecular classification of GISTs.

Prospective randomized controlled trial (phase III) to comparing laparoscopic distal gastrectomy with open distal gastrectomy for gastric adenocarcinoma (KLASS 01)

A randomized controlled trial to evaluate the long-term outcomes of laparoscopic distal gastrectomy for gastric cancer is currently ongoing in Korea. Patients with cT1N0M0-cT2aN0M0 (American Joint Committee on Cancer, 6th edition) distal gastric cancer were randomized to receive either laparoscopic or open distal gastrectomy. For surgical quality control, the surgeons participating in this trial had to have performed at least 50 cases each of laparoscopy-assisted distal gastrectomy and open distal gastrectomy and their institutions should have performed more than 80 cases each of both procedures each year. Fifteen surgeons from 12 institutions recruited 1,415 patients. The primary endpoint is overall survival. The secondary endpoints are disease-free survival, morbidity, mortality, quality of life, inflammatory and immune responses, and cost-effectiveness (ClinicalTrials.gov ID: NCT00452751).

Thoracoscopic esophagectomy for esophageal cancer: Feasibility and safety of robotic assistance in the prone position

OBJECTIVE To assess the feasibility and safety of robot-assisted thoracoscopic esophagectomy for esophageal cancer in the prone position. METHODS Twenty-one patients underwent robot-assisted thoracoscopic esophagectomy in the prone position by a surgical oncologist who had no prior experience with thoracoscopic esophagectomy. Hemodynamic and respiratory parameters were serially recorded to monitor changes in prone positioning. RESULTS All thoracoscopic procedures were completed with a robot-assisted technique followed by cervical esophagogastrostomy. R0 resection was achieved in 20 patients (95.2%), and the number of dissected nodes was 38.0 + or - 14.2. Robot console time was significantly reduced from 176.3 + or - 12.3 minutes in the initial 6 patients (group 1) to 81.7 + or - 16.5 minutes in the latter 15 patients (group 2) (P = .000). In group 2, there was less blood loss (P = .018), more patients could be extubated in the operating room (P = .004), and the number of dissected mediastinal nodes tended to be increased (P = .093). There was no incidence of pneumonia or 90-day mortality. Major complications included anastomotic leakage in 4 patients, vocal cord palsy in 6 patients, and intra-abdominal bleeding in 1 patient. The prone position led to an elevation of central venous pressure and mean pulmonary arterial pressure and a decrease in static lung compliance. However, cardiac index and mean arterial pressure were well maintained with the acceptable range of partial pressure of arterial oxygen and carbon dioxide. CONCLUSION Robotic assistance in the prone position is technically feasible and safe. Prone positioning was well tolerated, but preoperative risk assessment and meticulous anesthetic manipulation should be carried out.

Early Experiences of Robotic-assisted Laparoscopic Liver Resection

Purpose The surgical robotic system is superior to traditional laparoscopy in regards to 3-dimensional images and better instrumentations. Robotic surgery for hepatic resection has not yet been extensively reported. Patients and Methods Between March and May 2007, we performed 3 robot-assisted left lateral sectionectomies of the liver. Case 1 had a hepatocellular carcinoma (HCC), case 2 had colon cancer with liver metastasis, and case 3 had intrahepatic duct stones. Results All patients had successful operation and recovered without complications. Shorter length of hospital stays, earlier start of oral feeding and less amount of ascites were found. However, case 1 had recurrent HCC at 3 months after operation. Conclusion Robotic-assisted liver surgery is still a new field in its developing stage. In patients with small malignant tumors and benign liver diseases, robotic-assisted laparoscopic resection is feasible and safe. Through experience, the use of robotics is expected to increase in the treatment of benign diseases and malignant neoplsms. However, careful patient selection is important and long-term outcomes need to be evaluated.