Short-term outcomes of a multicentre randomized clinical trial comparing laparoscopic pylorus-preserving gastrectomy with laparoscopic distal gastrectomy for gastric cancer (the KLASS-04 trial).

BACKGROUND: There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer. METHODS: The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days. RESULTS: Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups. CONCLUSION: Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).

Laparoscopic sentinel node navigation surgery versus laparoscopic gastrectomy with lymph node dissection for early gastric cancer: short-term outcomes of a multicentre randomized controlled trial (SENORITA).

BACKGROUND: Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection. METHODS: The SENORITA trial was an investigator-initiated, open-label, parallel-assigned, non-inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3-year disease-free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study. RESULTS: A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach-preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien-Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647). CONCLUSION: The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND). MÉTODOS: El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio. RESULTADOS: Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien-Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647). CONCLUSIÓN: El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.

Randomized clinical trial of preoperative skin antisepsis with chlorhexidine gluconate or povidone-iodine.

BACKGROUND: Skin antiseptic agents are used to prevent surgical-site infection (SSI); few trials have reported the superiority of any specific agent in clean-contaminated abdominal surgery. This RCT was designed to compare the effectiveness of chlorhexidine gluconate and povidone-iodine. METHODS: Consecutive patients who underwent clean-contaminated upper gastrointestinal or hepatobiliary-pancreatic open surgery between 2011 and 2014 were assigned randomly to either chlorhexidine gluconate or povidone-iodine. The primary endpoint was the occurrence of SSI within 30 days of surgery. Secondary endpoints included causative organisms and risk factors for SSI. RESULTS: A total of 534 patients were randomized; 31 (5·8 per cent) developed an SSI. There was no difference in the overall SSI rate in the chlorhexidine gluconate and povidone-iodine groups: 15 of 267 (5·6 per cent) and 16 of 267 (6·0 per cent) respectively (P = 0·853). The most common causative organism was Enterococcus faecalis. In subgroup analysis, biliary-pancreatic surgery had a higher SSI rate (26 of 127, 20·5 per cent) than upper gastrointestinal (2 of 204, 1·0 per cent) and hepatic (3 of 203, 1·5 per cent) resection. Both age (60 years and over) and type of incision were associated with the risk of SSI. CONCLUSION: No difference was detected between chlorhexidine gluconate and povidone-iodine antiseptics for prevention of SSI. Registration number: NCT01495117 (http://www.clinicaltrials.gov).

Comparison of outcomes after laparoscopy-assisted and open total gastrectomy for early gastric cancer.

BACKGROUND: The aim of this study was to compare the results of laparoscopy-assisted total gastrectomy with those of open total gastrectomy for early gastric cancer. METHODS: Patients with gastric cancer who underwent total gastrectomy with curative intent in three Korean tertiary hospitals between January 2003 and December 2010 were included in this multicentre, retrospective, propensity score-matched cohort study. Cox proportional hazards regression models were used to evaluate the association between operation method and survival. RESULTS: A total of 753 patients with early gastric cancer were included in the study. There were no significant differences in the matched cohort for overall survival (hazard ratio (HR) for laparoscopy-assisted versus open total gastrectomy 0.96, 95 per cent c.i. 0.57 to 1.65) or recurrence-free survival (HR 2.20, 0.51 to 9.52). The patterns of recurrence were no different between the two groups. The severity of complications, according to the Clavien-Dindo classification, was similar in both groups. The most common complications were anastomosis-related in the laparoscopy-assisted group (8.0 per cent versus 4.2 per cent in the open group; P = 0.015) and wound-related in the open group (1.6 versus 5.6 per cent respectively; P = 0.003). Postoperative death was more common in the laparoscopy-assisted group (1.6 versus 0.2 per cent; P = 0.045). CONCLUSION: Laparoscopy-assisted total gastrectomy for early gastric cancer is feasible in terms of long-term results, including survival and recurrence. However, a higher postoperative mortality rate and an increased risk of anastomotic leakage after laparoscopic-assisted total gastrectomy are of concern.

Prognostic significance of peritoneal washing cytology in patients with gastric cancer.

BACKGROUND: Positive peritoneal washing cytology is a poor prognostic factor in patients with gastric cancer. The right therapeutic approach for this condition has not been well documented. METHODS: Patients who underwent surgery for gastric cancer with suspected serosal invasion and peritoneal washing cytology at the Korean National Cancer Centre between May 2001 and December 2009 were included in this retrospective study. Clinicopathological factors and overall survival were analysed with respect to the cytological results and presence of peritoneal metastases. Prognostic factors were analysed in patients with positive cytology but without overt peritoneal metastases. RESULTS: A total of 1072 patients were included in the analysis, of whom 900 had negative cytology (C0 group) and 172 had positive cytology (C1 group). No peritoneal metastases (P0) were found in 830 patients (92·2 per cent) in the C0 group. Peritoneal metastases (P1) were found in 76 patients (44·2 per cent) in the C1 group. Median overall survival times in the P0 C1, P1 C0 and P1 C1 subgroups were 20·0, 14·0 and 10·0 months respectively. Multivariable analysis of the P0 C1 subgroup revealed that clinical N0-2 category and gastric resection were significantly associated with better prognosis (median survival 24·0 versus 13·0 months for N0-2 versus N3, and 21·0 versus 4·0 months for resected versus non-resected). CONCLUSION: Positive washing cytology in patients with gastric cancer is a negative prognostic factor for patients with, as well as those without, overt peritoneal metastases. Resection is an option in patients with clinical stage N0-2 disease without peritoneal metastases but with a positive washing cytology finding.

Surgical stress after robot-assisted distal gastrectomy and its economic implications.

BACKGROUND: There is a lack of reports evaluating the outcomes of robotic gastrectomy and conventional laparoscopic surgery. The aim of this study was to compare the surgical stress response and costs of robot-assisted distal gastrectomy (RADG) with those of laparoscopy-assisted distal gastrectomy (LADG). METHODS: This prospective study compared a cohort of patients who had RADG with a cohort that underwent conventional LADG for early gastric cancer between March 2010 and May 2011. The surgical outcomes including Eastern Cooperative Oncology Group performance status and complications, surgical stress response and overall costs were compared between the two groups. RESULTS: Thirty patients were enrolled in the RADG group and 120 in the LADG group. There were no conversions. Median duration of operation was longer in the RADG group (218 (interquartile range 200-254) versus 140 (118-175) min; P < 0·001). Postoperative abdominal drain production was less (P = 0·001) and postoperative performance status was worse (P < 0·001) in the RADG group. C-reactive protein (CRP) levels on postoperative days 1 and 3, and interleukin (IL) 6 level on the third postoperative day, were lower in the LADG compared with the RADG group (CRP: P = 0·002 and P = 0·014 respectively; IL-6: P < 0·001). Costs for robotic surgery were much higher than for laparoscopic surgery (difference €3189). CONCLUSION: RADG did not reduce surgical stress compared with LADG. The substantial RADG costs due to robotic system expenses may not be justified.

Aspirin use and bleeding risk after endoscopic submucosal dissection in patients with gastric neoplasms.

BACKGROUND AND STUDY AIM: The risk of bleeding after endoscopic submucosal dissection (ESD) in patients with early gastric neoplasms who do not discontinue aspirin for the procedure has not been established. We aimed to investigate whether post-ESD gastric bleeding is increased in patients who take aspirin. PATIENTS AND METHODS: Patients who underwent ESD for early gastric neoplasms at the National Cancer Center Hospital, Korea, between November 2008 and January 2011 were enrolled. The risk of post-ESD bleeding was evaluated using Poisson regression analysis. RESULTS: We categorized 514 patients into three groups according to aspirin intake at the time of the procedure: patients who never used aspirin (n=439), patients who interrupted aspirin use for 7 days or more (n=56), and patients who continuously used aspirin (n=19). Post-ESD bleeding occurred in 4.1% (21/514) overall, and was more frequent in continuous aspirin users (4/19 [21.1%]) than in those who never used aspirin (15/439 [3.4%]) (P=0.006) and those with interrupted aspirin use (2/56 [3.6%]) (P=0.033). Multivariate analysis showed that use of aspirin by itself was associated with post-ESD bleeding (relative risk [RR] 4.49; 95% confidence interval [95%CI] 1.09-18.38). The resumption of clopidogrel combined with aspirin use (RR 26.71, 95%CI 7.09-100.53), and increased iatrogenic ulcer size (RR 1.52, 95%CI 1.14-2.02), were significantly associated with post-ESD bleeding. CONCLUSIONS: Continuous aspirin use increases the risk of bleeding after gastric ESD. Aspirin use should be stopped in patients with a low risk for thromboembolic disease to minimize bleeding complications.

CYP2A6 and ERCC1 polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients.

BACKGROUND: We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6)/excision repair cross-complementation group 1 (ERCC1)/X-ray repair cross-complementing group 1(XRCC1) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin. METHODS: Among MGC patients (n=108), who received S-1 (40 mg m(-2) b.i.d., days 1-14) and cisplatin (60 mg m(-2), day 1) every 3 weeks, we analysed the wild-type allele (W) and variants (V) of CYP2A6 (*4, *7, *9, *10), and the polymorphisms of ERCC1 (rs11615, rs3212986) and XRCC1 (rs25487). RESULTS: Patients having fewer CYP2A6 variants had better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4=66.7 vs 58.3 vs 32.3%; P=0.008), time to progression (TTP) (7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A (rs3212986) was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (4.4 vs 7.6 vs 7.9 months) (P=0.012). Patients carrying both risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C) vs those carrying none showed an adjusted odds ratio of 0.113 (P=0.004) for response, and adjusted hazard ratios of 3.748 (P=0.0001) for TTP and 2.961 (P=0.006) for death. CONCLUSION: Polymorphisms of CYP2A6 and ERCC1 19442C>A correlated with the efficacy of S-1/cisplatin.

Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results.

BACKGROUND: The aim of this study was to investigate the efficacy and safety of S-1/irinotecan/oxaliplatin (TIROX) in metastatic gastric cancer (MGC) and the association between treatment outcome and uridine diphosphate-glucuronosyltransferase (UGT) 1A polymorphisms. PATIENTS AND METHODS: Patients with previously untreated MGC received S-1 40 mg/m(2) b.i.d. on days 1-14 and irinotecan 150 mg/m(2) plus oxaliplatin 85 mg/m(2) on day 1 every 3 weeks. RESULTS: Forty-four patients were enrolled. In intent-to-treat analysis, the objective response rate was 75%, including the complete response (CR) rate of 14%. The median time to progression and overall survival was 10.2 and 17.6 months, respectively. Ten (26%) of the 39 patients with primary gastric tumor showed biopsy-confirmed gastric CR. Grade 3/4 neutropenia developed in 66% of patients and grade 3 febrile neutropenia in 16%. The most common grade 3 nonhematologic toxic effects were abdominal pain (18%), anorexia (16%), and diarrhea (14%). UGT1A polymorphisms were associated with significantly higher incidence of grade 4 leukopenia (UGT1A1*6), neutropenia (UGT1A1*6, UGT1A6*2, and UGT1A7*3), grade 3/4 febrile neutropenia (UGT1A1*6), and grade 3 abdominal pain (UGT1A1*6). CONCLUSIONS: The TIROX regimen induced marked tumor reduction and promising survival with a manageable toxicity profile in MGC patients. UGT1A genotype may be predictive of TIROX toxicity.

Risk of high-grade dysplasia or carcinoma in gastric biopsy-proven low-grade dysplasia: an analysis using the Vienna classification.

BACKGROUND AND AIMS: Therapeutic guidelines have not yet been established for low-grade gastric adenomas/dysplasias (LGD), which have a low risk of progression to high-grade adenomas/dysplasias (HGD) or to invasive carcinomas. This study aimed to evaluate risk factors for HGD/carcinoma that indicate a need for resection in biopsy-proven LGD lesions. PATIENTS AND METHODS: In total, 236 LGD lesions from 208 consecutive patients treated with endoscopic resection (ER) were retrospectively studied between 2004 and 2008. The Vienna classification was used for histological diagnosis. A generalized estimating equation (GEE) logistic regression model was used for multivariate analysis. RESULTS: Among the 236 LGD lesions, the final pathology diagnosed 9 (3.8 %) as invasive carcinoma (category 5), 71 (30.1 %) as HGD (category 4), 148 (62.7 %) as LGD (category 3), and 8 (3.4 %) as negative/indefinite for dysplasia (category 1/2). Lesions ≥ 1 cm were classified as HGD/carcinoma in 39.4 % of patients (65/165). Multivariate analysis indicated that size of ≥ 1 cm (OR 1.93 [95 % CI, 1.06 - 3.52]), depressed morphology (OR 3.81 [95 % CI, 1.22 - 11.9]), and erythema (OR 2.49 [95 % CI, 1.31 - 4.72]) were significantly associated with HGD/carcinoma. The OR increased to 47.6 (95 % CI, 4.27 - 530.65) when the risk factors were all positive. The sensitivity and negative predictive value for ≥ 1 risk factors were 93.8 % and 90.9 %, respectively. As the number of risk factors of a lesion increased, the specificity and positive predictive value also increased. CONCLUSIONS: Endoscopic resection can be recommended if a low-grade dysplastic lesion has at least one of the following risk factors: depressed morphology, surface erythema, or a size of 1 cm or greater. For lesions that have none of the three risk factors, follow-up endoscopy is recommended.

Risk factors for lymph node metastasis in patients with early gastric cancer and signet ring cell histology.

BACKGROUND: Early gastric cancer with signet ring cell histology has been reported as a favourable histological type. The aim of this study was to identify risk factors associated with lymph node metastasis in patients with this type of early gastric cancer. METHODS: A cross-sectional study of patients with early gastric cancer with differentiated and signet ring cell histology undergoing surgery was conducted. Risk factors were evaluated using multiple logistic regression analysis with odds ratios and 95 per cent confidence intervals. RESULTS: In 1362 patients undergoing gastrectomy for early gastric cancer, the rate of lymph node metastasis was similar for tumours with signet ring cell and differentiated histological findings (10.7 versus 9.0 per cent respectively; P = 0.307). Logistic regression analysis showed that depth of tumour invasion was predictive of lymph node metastasis in patients with signet ring cell histology (P < 0.001). Tumour size was not associated with lymph node metastasis in either univariable or multivariable analysis. Lesions smaller than 2 cm were not uncommon in patients with signet ring cell gastric tumours and lymph node metastases (six of 48; 13 per cent). CONCLUSION: Patients with early gastric cancer with signet ring cell-type histology are probably best treated by gastrectomy with lymph node dissection.

Learning curve for identification of sentinel lymph node based on a cumulative sum analysis in gastric cancer.

BACKGROUND/AIMS: Lymph node metastasis is the most important point to consider when deciding on the modality of resection in patients with early gastric cancer. This study was conducted to evaluate the learning curve for identification of sentinel lymph nodes in patients with gastric cancer. METHODS: The investigators included the results from 2 prospective series of sentinel lymph node mapping. Cumulative sum (CUSUM) analysis was performed to assess the learning curves for identification of sentinel lymph nodes at CUSUM target success rates of 95%. RESULTS: One surgeon performed 135 sentinel lymph node mappings for 2 prospective series. The success rate exceeded 90%. The learning period for gastric cancer sentinel node mapping was calculated to be 26 cases for achieving a 95% success rate. Multiple logistic regression analysis for successful detection of sentinel nodes showed that surgical experience of sentinel lymph node mapping was an independent factor for successful detection of sentinel nodes. CONCLUSIONS: This study suggests that the learning period for identification of sentinel lymph nodes in gastric cancer would be 26 cases. In clinical trials for gastric cancer with sentinel lymph node mapping, the learning curve should be considered to minimize bias due to surgical factors.

Phase I/II study of S-1 combined with weekly docetaxel in patients with metastatic gastric carcinoma.

We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1-14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30-45 mg m(-2) b.i.d.) and docetaxel (25-40 mg m(-2)); MTD was 45 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel and RD was 40 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8-79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9-8.1) and 13.7 months (95% CI: 9.9-17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.

Alpha-fetoprotein is a significant prognostic factor for gastric cancer: Results from a propensity score matching analysis after curative resection.

BACKGROUND: Prognosis of alpha-fetoprotein positive gastric cancer (AFPP-GC) remains elusive so far due to disparities in cohort size and baseline characteristics in previous studies. A propensity score matching (PSM) analysis as well as multivariable model was performed for unbiased evaluation of the outcome in AFPGC. METHODS: Among 3034 gastric cancer patients who underwent curative gastric cancer surgery (R0, M0) at the National Cancer Center, Korea between 2002 and 2007, we identified 97 patients being positive for AFP either by elevation of serum-AFP levels >10 µg/L or by immunohistochemical staining. Due to marked disparities in baseline characteristics and cohort size, propensity-score-matching was performed which matched 87 AFPP-GC patients to the same number of AFP-negative gastric cancer (AFPN-GC) patients. Baseline characteristics were compared using χ2-test. Survival curves were compared using the Kaplan-Meier-method and multivariable regression analysis was performed to evaluate the effect of AFP-positivity while adjusting the effects of confounding variables. RESULTS: AFPP-GC and AFPN-GC patients revealed marked disparities in patient cohorts. After PSM, groups were balanced for age, sex, tumor size, BMI, tumor location, grade of differentiation, presence of lymphatic vessel infiltration (LVI), Lauren histologic type and stage distribution. In multivariable regression analysis of the PSM-groups, only AFP-positivity and pathologic stage were predictive for overall survival (HR 2.98, CI 95% {1.7-5.1}, p < 0.0001). Five-year-survival rates were significantly worse for AFPP-GC patients (57.9% vs. 76.1%, p = 0.014). Recurrence was significantly more frequent in AFPP-GC patients (p = 0.003). CONCLUSION: AFP can be considered as an independent negative predictor of overall and recurrence-free survival in patients with gastric cancer.

Correlation between lymph node count and survival and a reappraisal of lymph node ratio as a predictor of survival in gastric cancer: A multi-institutional cohort study.

PURPOSE: The purpose of this study is to evaluate the correlation between lymph node count (LNC) and survival and to evaluate whether lymph node ratio (LNR) which is related to LNC is a better predictor of survival for gastric cancer than the N category of UICC/AJCC through a multi-institutional cohort study. METHODS: The study cohort included 3284 patients from eight institutions. Lower and upper quartiles of LNC were used for comparisons. The cut-off values (0, 0.06, 0.27, and 0.49) for the LNR categories were based on Classification and Regression Trees techniques. Akaike information criteria (AIC) for Cox regression models was used to evaluate goodness of fit between competing predictor variables (LNR vs. N category). RESULTS: The 5-year disease-specific survival (DSS) rates of lower and upper quartiles of LNC were 82.2% and 84.8%. In the subgroup analysis of pN category, the upper quartile of LNC showed better survival than the lower quartile in pN2, pN3a, and pN3b subgroups. Regarding LNR, 5-year DSS of LNR 0, 0-0.06, 0.06-0.27, 0.27-0.49, and >0.49 was 95.3%, 88.7%, 70.6%, 42.7%, and 17.2% respectively. Multivariate analysis showed that pT, pN, LNR, residual tumor status, distant metastasis, and tumor differentiation significantly affected survival. The analysis also confirmed superiority of LNR compared with N category in the AIC analysis. CONCLUSION: Higher LNC correlated with better survival in patients with pN2, pN3a, and pN3b gastric cancer. Our data indicate that LNR is a better predictor of survival than N category of UICC/AJCC.

Who may benefit from robotic gastrectomy?: A subgroup analysis of multicenter prospective comparative study data on robotic versus laparoscopic gastrectomy.

AIMS: Robotic gastrectomy for gastric cancer has been proven to be a feasible and safe minimally invasive procedure. However, our previous multicenter prospective study indicated that robotic gastrectomy is not superior to laparoscopic gastrectomy. This study aimed to identify which subgroups of patients would benefit from robotic gastrectomy rather than from conventional laparoscopic gastrectomy. METHODS: A prospective multicenter comparative study comparing laparoscopic and robotic gastrectomy was previously conducted. We divided the patients into subgroups according to obesity, type of gastrectomy performed, and extent of lymph node dissection. Surgical outcomes were compared between the robotic and laparoscopic groups in each subgroup. RESULTS: A total of 434 patients were enrolled into the robotic (n = 223) and laparoscopic (n = 211) surgery groups. According to obesity and gastrectomy type, there was no difference in the estimated blood loss (EBL), number of retrieved lymph nodes, complication rate, open conversion rate, and the length of hospital stay between the robotic and laparoscopic groups. According to the extent of lymph node dissection, the robotic group showed a significantly lower EBL than did the laparoscopic group after D2 dissection (P = 0.021), while there was no difference in EBL in patients that did not undergo D2 dissection (P = 0.365). CONCLUSION: Patients with gastric cancer undergoing D2 lymph node dissection can benefit from less blood loss when a robotic surgery system is used.

Comparative study of the subserosal versus submucosal dye injection method for sentinel node biopsy in gastric cancer.

AIMS: To determine the most efficient injection method for a sentinel node (SN) biopsy in gastric cancer. METHODS: Gastric adenocarcinoma patients without serosal invasion and distant metastasis were prospectively enrolled in this study. Isosulfan blue was injected into the subserosa (SS) of the first set of 71 consecutive patients and an intraoperative endoscopic submucosal (SM) injection of the same dye was injected into the second set of 50 consecutive patients. After the biopsy of blue-stained SNs, a gastrectomy with a D2 lymphadenectomy was performed. All dissected lymph nodes were evaluated for metastasis. The results of the SN biopsies were compared between the SS and SM dye injection methods. RESULTS: Detection rate (0.92 vs 0.94), mean number of SNs (2.5 vs 2.9) and sensitivity (0.61 vs 0.46) of the SN biopsies were not significantly different between the SS and SM injection methods (P>0.05). The operation time was significantly shorter in the SS than the SM injection method (159.7 vs 172.7 min, P=0.030). CONCLUSIONS: Both injection methods were equally efficient in their roles for a SN biopsy in gastric cancer. However, the SS injection method was more preferable due to its easy technique and short operation time.

The role of hand-assisted laparoscopic distal gastrectomy for distal gastric cancer.

BACKGROUND: The aim of this study was to evaluate the role of hand-assisted distal gastrectomy (HALDG) for gastric cancer. METHODS: This study prospectively enrolled 16 patients who underwent HALDG for early gastric cancer and matched them individually by sex, age, and body mass index to patients who underwent laparoscopically assisted distal gastrectomy (LADG) or open distal gastrectomy (ODG). Surgical outcomes were compared among the surgical methods. RESULTS: The mean operating time was the longest for the HALDG group, whereas wound size of the HALDG group was intermediate between that of the LADG and the ODG groups. The other surgical outcomes, such as the number of harvested lymph nodes, were not different among the groups. CONCLUSIONS: According to the findings, HALDG may not be as beneficial for patients with early gastric cancer as has been previously suggested. However, because of easier hand-eye coordination, HALDG may be an excellent bridge learning technique as a surgeon gains experience in laparoscopic gastrectomy.

Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor.

The activation of coagulation, angiogenesis and inflammatory cytokines are considered to be related with tumour growth and metastasis. We investigated the plasma levels of platelet microparticles (PMP), vascular endothelial growth factor (VEGF), IL-6, and the chemokine RANTES in patients with gastric cancer (n=109) and in healthy controls (n=29). The plasma levels of PMP, IL-6 and RANTES were significantly higher in the patients than in the healthy controls, and plasma levels of PMP, VEGF, IL-6 and RANTES were significantly higher in patients with stage IV disease than those in patients with stage I or stage II/III. In terms of predicting distant metastasis, the sensitivities of PMP, VEGF, IL-6 and RANTES were 93.3%, 56.7%, 70.0% and 81.8%, respectively, and the corresponding specificities were 91.1%, 64.6%, 79.7% and 50.0%. Among these parameters, PMP had the highest diagnostic accuracy. Significant correlations were found between PMP, VEGF, IL-6 and RANTES. This study demonstrates that the plasma levels of PMP, VEGF, IL-6 and RANTES were markedly increased in patients with stage IV disease, and that these increased plasma levels of IL-6, RANTES, and especially PMP, might be useful for identifying metastatic gastric patients.

Prediction of lymph nodes metastasis by sentinel node biopsy in gastric cancer.

AIM: The application of sentinel node (SN) biopsy in gastric cancer remains controversial. In this study, detection rate and predictive values of SN biopsy were determined to evaluate its feasibility in gastric cancer. Various clinicopathologic features were also analysed to determine the factors affecting the detection rate and predictive values. METHODS: Seventy-one gastric adenocarcinoma patients without serosal invasion and distant metastasis, were studied. One percent isosulfan blue stained nodes were defined as SNs, and standard gastrectomy with D2 lymphadenectomy was performed. All lymph nodes were studied by hematoxylin and eosin staining. RESULTS: SNs were identified in 65 of 71 patients and average number of SNs per patient was 2.5 (range 1-8). Among the 65 patients with SNs, metastatic SNs were found in 11 and the remaining 54 were free of metastasis. In eight of the 11 patients with metastasis of the SNs, metastases were also identified in non-SNs. CONCLUSIONS: SN biopsy is feasible in early stage gastric cancer. However, complementary procedures may be needed to improve the detection rate and predictive values. SNs biopsy results should be treated with caution in male patients and for tumours at the upper part of stomach due to the low detection rate.