Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin ß1.

BACKGROUND: Tumor cells of diffuse-type gastric cancer (DGC) are discohesive and infiltrate into the stroma as single cells or small subgroups, so the stroma significantly impacts DGC progression. Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma. Here, we identified CAF-specific secreted molecules and investigated the mechanism underlying CAF-induced DGC progression. METHODS: We conducted transcriptome analysis for paired normal fibroblast (NF)-CAF isolated from DGC patient tissues and proteomics for conditioned media (CM) of fibroblasts. The effects of fibroblasts on cancer cells were examined by transwell migration and soft agar assays, western blotting, and in vivo. We confirmed the effect of blocking tubulointerstitial nephritis antigen-like 1 (TINAGL1) in CAFs using siRNA or shRNA. We evaluated the expression of TINAGL1 protein in frozen tissues of DGC and paired normal stomach and mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue using RNA in-situ hybridization (RNA-ISH). RESULTS: CAFs more highly expressed TINAGL1 than NFs. The co-culture of CAFs increased migration and tumorigenesis of DGC. Moreover, CAFs enhanced the phosphorylation of focal adhesion kinase (FAK) and mesenchymal marker expression in DGC cells. In an animal study, DGC tumors co-injected with CAFs showed aggressive phenotypes, including lymph node metastasis. However, increased phosphorylation of FAK and migration were reduced by blocking TINAGL1 in CAFs. In the tissues of DGC patients, TINAGL1 was higher in cancer than paired normal tissues and detected with collagen type I alpha 1 chain (COL1A1) in the same spot. Furthermore, high TINAGL1 expression was significantly correlated with poor prognosis in several public databases and our patient cohort diagnosed with DGC. CONCLUSIONS: These results indicate that TINAGL1 secreted by CAFs induces phosphorylation of FAK in DGC cells and promotes tumor progression. Thus, targeting TINAGL1 in CAFs can be a novel therapeutic strategy for DGC.

Thromboembolic events in patients who received adjuvant chemotherapy for gastric cancer: a single-center retrospective study.

BACKGROUND: Thromboembolic events (TEEs) are significant adverse events that can cause serious morbidities and mortality in cancer patients receiving chemotherapy. Patients with gastric cancer (GC) treated with palliative chemotherapy have been reported to experience a TEE incidence of 5-27%. However, very few reports have addressed TEEs in adjuvant chemotherapy (AC) for GC. METHODS: This study retrospectively analyzed 611 GC patients (stage II: 309, III: 302) who started AC with capecitabine/oxaliplatin (167 patients) or S-1 (444 patients) after undergoing curative resection between January 2013 and June 2020 at a single center. The incidence of TEEs during AC or within 1 year after AC completion was investigated, while analyzing the factors that influenced the TEEs' occurrence. RESULTS: TEEs were confirmed in 20 patients (3.3%), and TEEs occurred in almost all patients in the S-1 group (19 patients). The most common TEE types were cerebral infarction and pulmonary thromboembolism (five patients each). Although old age (≥ 70 years, p < 0.0001), S-1 treatment (p = 0.021), and hypertension (p = 0.017) were identified as significant risk factors for TEEs in univariate analysis, only old age showed a statistically significant correlation with TEEs' occurrence in multivariate analysis (odds ratio: 3.07; 95% confidence interval 1.11-8.48; p = 0.031). CONCLUSIONS: TEEs occurred in fewer patients with GC who had been treated with AC than patients who had received palliative chemotherapy in previous reports. However, elderly GC patients who are undergoing AC require more careful surveillance for possible TEEs, considering relatively higher incidence of them.

Long-term Comparison of Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Propensity Score-weighted Analysis of 2084 Consecutive Patients.

OBJECTIVE: To compare long-term outcomes between robotic and LG approaches using propensity score weighting based on a generalized boosted method to control for selection bias. SUMMARY OF BACKGROUND DATA: Minimally invasive surgical approaches for GC are increasing, yet limited evidence exists for long-term outcomes of robotic gastrectomy (RG). METHODS: Patients (n = 2084) with GC stages I-III who underwent LG or RG between 2009 and 2017 were analyzed. Generalized boosted method was used to estimate a propensity score derived from all available preoperative characteristics. Long-term outcomes were compared using the adjusted Kaplan-Meier method and the weighted Cox proportional hazards regression model. RESULTS: After propensity score weighting, the population was balanced. Patients who underwent RG showed reduced blood loss (16 mL less, P = 0.025), sufficient lymph node harvest from the initial period, and no changes in surgical outcomes over time. With 52-month median follow-up, no difference was noted in 5-year overall survival in unweighted [91.5% in LG vs 94% in RG; hazard ratio (HR), 0.71; 95% confidence interval (CI), 0.46-1.1; P = 0.126] and weighted populations (94.2% in LG vs 93.2% in RG; HR, 0.88; 95% CI, 0.52-1.48; P = 0.636). There were no differences in 5-year recurrence-free survival (RFS), with unweighted 5-year RFS of 95.4% for LG and 95.2% for RG (HR, 0.95; 95% CI, 0.55-1.64; P = 0.845) and weighted 5-year RFS of 96.3% for LG and 95.3% for RG (HR, 1.24; 95% CI, 0.66-2.33; P = 0.498). CONCLUSIONS: After balancing covariates, RG demonstrated reliable surgical outcomes from the beginning. Long-term survival after RG and LG for GC was similar.

Prediction of Survival Outcomes Based on Preoperative Clinical Parameters in Gastric Cancer.

BACKGROUND: Few current preoperative risk assessment tools provide essential, optimized treatment for gastric cancer. The purpose of this study was to develop and validate a nomogram that uses preoperative data to predict survival and risk assessments. METHODS: A survival prediction model was constructed using data from a developmental cohort of 1251 patients with stage I to III gastric cancer who underwent curative resection between January 2005 and December 2008 at Ajou University Hospital, Korea. The model was internally validated for discrimination and calibrated using bootstrap resampling. To externally validate the model, data from a validation cohort of 2012 patients with stage I to III gastric cancer who underwent surgery at multiple centers in Korea between January 2001 and June 2006 were analyzed. Analyses included the model's discrimination index (C-index), calibration plots, and decision curve that predict overall survival. RESULTS: Eight independent predictors, including age, sex, clinical tumor size, macroscopic features, body mass index, histology, clinical stages, and tumor location, were considered for developing the nomogram. The discrimination index was 0.816 (adjusted C-index) in the developmental cohort and 0.781 (adjusted C-index) in the external validation cohort. Additionally, in both the developmental and validation datasets, age and tumor size were significantly correlated with each other and were independent indicators for survival (P < 0.05). CONCLUSIONS: We developed a new nomogram by using the most common and significant preoperative parameters that can help to identify high-risk patients before treatment and help clinicians to make appropriate decisions for patients with stage I to III gastric cancer.

Quality of life after laparoscopic sentinel node navigation surgery in early gastric cancer: a single-center cohort study.

OBJECTIVE: To investigate the quality of life (QOL) of patients after laparoscopic sentinel node navigation surgery (SNNS) compared to conventional laparoscopy-assisted distal gastrectomy (LADG) in early gastric cancer patients. METHODS: Patients recruited for laparoscopic SNNS surgery between July 2010 and April 2013 were assessed for their QOL. A historical control group was established, consisting of patients who underwent conventional LADG with radical lymphadenectomy from the same institution. QOL questionnaire was taken serially from preoperative week 1 until 12 months postoperatively (1, 3, 6, and 12 months) using the Korean version of the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire-core (QLQ-C30) and gastric cancer-specific questionnaire (STO22). RESULTS: A total of 80 prospectively gathered patients who received SNNS were categorized into the comparison group (SNNS group). The QOL was compared with 78 patients identified to have received LADG from the gastric cancer database of our institution and were sorted into the control group (LADG group). In QLQ-C30, SNNS group showed better functioning scales in all except role functioning and better scores from the symptom scales in fatigue, insomnia, and diarrhea compared to the LADG group. In QLQ-STO22, scores on dysphagia, eating restriction, anxiety, and body image disturbance were better in SNNS group. CONCLUSIONS: Postoperative QOL in laparoscopic gastrectomy combined with SNNS is superior compared to conventional laparoscopic distal gastrectomy in patients with stage I gastric cancer.

Clinical pathway for enhanced recovery after surgery for gastric cancer: A prospective single-center phase II clinical trial for safety and efficacy.

BACKGROUND: We aimed to evaluate the safety and efficacy of a clinical pathway (CP) for enhanced recovery after surgery (ERAS) in gastric cancer patients, including early oral feeding and discharge on postoperative day 4. METHODS: We performed a prospective, single-center, phase II clinical trial. Based on proposed indications for an ERAS CP in our retrospective study, we enrolled 133 patients younger than 65 years who were undergoing minimally invasive subtotal gastrectomy. The primary endpoint was the ERAS CP completion rate. Secondary endpoints included complication, mortality, hospital stay, and readmission. RESULTS: Among 133 patients, six patients were dropped out from this study. The ERAS CP completion rate (77.2%, 98 of 127) was comparable to the historical control group that completed a conventional CP (85.4%, P = .085). The postoperative complication incidence (13.4%, 15 of 127) was also similar to that of the conventional CP group (9.5%, P = .174). We identified reduced hospital stays (4.7 ± 1.3 vs 7.2±2.3 days; P < .001) and lower hospital costs ($7771 vs 8539; P < .001) in the ERAS CP group compared with the conventional CP group. CONCLUSIONS: An ERAS CP can be safely and effectively adopted for patients with gastric cancer without increasing the complication rate and could shorten hospital stays. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01642953).

Inhibiting the GAS6/AXL axis suppresses tumor progression by blocking the interaction between cancer-associated fibroblasts and cancer cells in gastric carcinoma.

BACKGROUND: The effects of cancer-associated fibroblasts (CAF) on the progression of gastric carcinoma (GC) has recently been demonstrated. However, agents targeting the interaction between CAF and GC cells have not been applied in a clinical setting. Here, we examined if inhibition for Axl receptor tyrosine kinase (AXL) can suppress CAF-induced aggressive phenotype in GC. METHODS: We investigated the function of CAF-derived growth arrest-specific 6 (GAS6), a major ligand of AXL, on the migration and proliferation of GC cells. The effect of the AXL inhibitor, BGB324, on the CAF-induced aggressive phenotype of GC cells was also investigated. In addition, we performed immunohistochemistry to examine the expression of phosphorylated AXL protein in 175 GC tissues and evaluated its correlation with the prognosis. RESULTS: The qPCR and western blot analysis showed that GAS6 expression was higher in CAF relative to other cells. We found that co-culture with CAF increased the phosphorylation of AXL (P-AXL), differentiation into a mesenchymal-like phenotype, and cell survival in GC cell lines. When the expression of AXL was genetically inhibited in GC cells, the effect of CAF was reduced. BGB324, a small molecule inhibitor of AXL, suppressed the effects of CAF on GC cell lines. In GC tissues, high levels of P-AXL were significantly associated with poor overall survival (P = 0.022). CONCLUSIONS: We concluded that CAF are a major source of GAS6 and that GAS6 promotes an aggressiveness through AXL activation in GC. We suggested that an AXL inhibitor may be a novel agent for GC treatment.

Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer.

BACKGROUND: Although the tumor stroma in solid tumors like gastric cancer (GC) plays a crucial role in chemo-resistance, specific targets to inhibit the interaction between the stromal and cancer cells have not yet been utilized in clinical practice. The present study aims to determine whether cancer-associated fibroblasts (CAFs), a major component of the tumor stroma, confer chemotherapeutic resistance to GC cells, and to discover potential targets to improve chemo-response in GC. METHODS: To identify CAF-specific proteins and signal transduction pathways affecting chemo-resistance in GC cells, secretome and transcriptome analyses were performed. We evaluated the inhibiting effect of CAF-specific protein in in vivo and in vitro models and investigated the expression of CAF-specific protein in human GC tissues. RESULTS: Secretome and transcriptome data revealed that interleukin-6 (IL-6) is a CAF-specific secretory protein that protects GC cells via paracrine signaling. Furthermore, CAF-induced activation of the Janus kinase 1-signal transducer and activator of transcription 3 signal transduction pathway confers chemo-resistance in GC cells. CAF-mediated inhibition of chemotherapy-induced apoptosis was abrogated by the anti-IL-6 receptor monoclonal antibody tocilizumab in various experimental models. Clinical data revealed that IL-6 was prominently expressed in the stromal portion of GC tissues, and IL-6 upregulation in GC tissues was correlated with poor responsiveness to chemotherapy. CONCLUSIONS: Our data provide plausible evidence for crosstalk between GC cells and CAFs, wherein IL-6 is a key contributor to chemoresistance. These findings suggest the potential therapeutic application of IL-6 inhibitors to enhance the responsiveness to chemotherapy in GC.

Neural Invasion is a Significant Contributor to Peritoneal Recurrence in Signet Ring Cell Gastric Carcinoma.

BACKGROUND: Gastric signet ring cell carcinoma (SRC) has shown a favorable outcome in early stages but has a worse prognosis than non-SRC in advanced stages. However, the cause for this stage-dependent prognostic impact has not been determined. This study aimed to compare clinicopathologic features and recurrence patterns between gastric SRC and non-SRC in a cohort of Eastern patients. METHODS: This study reviewed the prospectively collected data of 764 patients undergoing curative resection for gastric cancer from 2005 to 2008. The demographics, clinicopathologic characteristics, disease-specific survival (DSS) rate, and recurrence-free survival (RFS) rate of the patients were analyzed. RESULTS: The SRC patients (n = 176) had a worse prognosis than the non-SRC patients (n = 588), especially in stages T3 and T4. Peritoneal recurrence and the incidence of neural invasion (NI) were significantly increased in the SRC patients, albeit only in stages T3 and T4. In the T3 and T4 patients with NI, peritoneal recurrence occurred more frequently in SRC than in non-SRC (28.7% vs. 13.7%; p = 0.001), but not in the T3 and T4 patients without NI. Only in the patients with NI, SRC led to a significantly shorter DSS (67.6 vs. 90.7 months; p = 0.008) and RFS (67.1 vs. 80.3 months; p = 0.036) than non-SRC. CONCLUSIONS: This report is the first to present the relationship between NI and peritoneal recurrence as the cause of stage-dependent prognoses for SRC. A better understanding of NI may lend insight into cancer spread and recurrence, especially in gastric SRC.

Long-Term Oncologic Outcomes of Laparoscopic Sentinel Node Navigation Surgery in Early Gastric Cancer: A Single-Center, Single-Arm, Phase II Trial.

BACKGROUND: Sentinel node navigation surgery (SNNS) in early gastric cancer (EGC) is technically feasible according to previous literature, however its long-term oncologic safety has not been reported. METHODS: A single-center, single-arm, phase II trial was conducted to determine the oncologic outcomes of laparoscopic sentinel node (SN) biopsy in clinical stage T1N0M0 gastric cancer patients. Cases with positive SNs on intraoperative pathologic examination underwent conventional gastrectomy with radical lymphadenectomy (SN-positive group), whereas those with negative SNs underwent laparoendoscopic-limited gastric resections without further lymph node dissections (SN-negative group). The primary endpoint was 3-year relapse-free survival. RESULTS: Between July 2010 and April 2013, 113 patients were enrolled, with 100 patients being included in the final analysis. SNs were detected in 99 patients. The mean number of identified SNs was 6.1 ± 3.9. Eleven patients were included in the SN-positive group and 89 in the SN-negative group. After a median follow-up period of 46.4 months, four patients died and three showed cancer recurrence. All recurrences occurred on the remnant stomach after endoscopic submucosal resection or wedge resection in the SN-negative group. The 3-year relapse-free and overall survival rates were 96.0% (95% confidence interval [CI] 92.2-100.0%) and 98.0% (95% CI 95.2-100.0%), respectively. CONCLUSIONS: Our results indicate that laparoscopic SNNS may be oncologically safe in EGC. Limited gastric resections should be carefully performed to prevent local recurrence in SN-negative cases. A randomized controlled trial is needed based on the present study.

Roux Stasis Syndrome and Gastric Food Stasis After Laparoscopic Distal Gastrectomy with Uncut Roux-en-Y Reconstruction in Gastric Cancer Patients: A Propensity Score Matching Analysis.

BACKGROUND: Uncut Roux-en-Y gastrojejunostomy (uRYGJ) was developed to prevent slow peristalsis in the Roux limb after Roux-en-Y gastrojejunostomy (RYGJ). This study compared the incidence of Roux stasis syndrome (RSS) and severe gastric food stasis in gastric cancer patients who underwent RYGJ or uRYGJ after laparoscopic curative distal gastrectomy. METHODS: Between January 2006 and June 2012, 319 patients underwent RYGJ or uRYGJ. After covariates were adjusted by propensity score matching, 39 patients in the RYGJ group and 65 patients in the uRYGJ group were included in the final analysis. RSS was defined as the presence of symptoms, such as nausea, vomiting, and abdominal fullness, requiring refasting without ileus or obstruction within 30 days post-surgery. Gastric food stasis was measured endoscopically at 1 and 3 years after gastrectomy. RESULTS: Operative outcomes and morbidities were similar between the two groups, whereas the incidence of RSS was higher in the RYGJ group than in the uRYGJ group, although the difference was not significant (7.7 vs. 0%; odds ratio (OR) 0.157; 95% confidence interval (CI) 0-1.059, p = 0.111). Comparison of endoscopic findings revealed that severe gastric stasis 1 year after surgery was significantly less frequent in the uRYGJ group (46.2 vs. 13.8%; OR 0.247; 95% CI 0.102-0.599, p = 0.002). The same result was reproduced 3 years after surgery (39.4 vs. 15.5%; OR 0.279; 95% CI 0.088-0.882, p = 0.030). CONCLUSIONS: Compared with RYGJ, uRYGJ after laparoscopic distal gastrectomy is a safe and effective procedure for preventing severe postoperative gastric food stasis.

Surgeon's Experience Overrides the Effect of Hospital Volume for Postoperative Outcomes of Laparoscopic Surgery in Gastric Cancer: Multi-institutional Study.

BACKGROUND: Hospital volume is known to be a crucial factor in reducing postoperative morbidity and mortality in laparoscopic gastrectomy for gastric cancer. However, it is unclear whether surgeon's individual experience can overcome the effect of hospital volume. METHODS: Clinicopathologic data of initial 50 laparoscopic gastrectomy cases were collected from six gastric cancer surgeons. Half of the six surgeons worked in high-volume centers, and the other half worked in low-volume hospitals. Perioperative outcomes were compared between the high-volume centers and the low-volume hospitals. RESULTS: Three low-volume hospitals in this study contained significantly more male and older patients with a higher American Society of Anesthesiologists score than high-volume centers. Although high- and low-volume hospitals mainly used laparoscopy-assisted and totally laparoscopic approach, respectively, there were no differences between the two groups in the extent of resection, operating time, estimated blood loss, and number of collected lymph nodes. Postoperative recovery such as duration to soft diet and hospital stay did not differ between the high- and the low-volume hospitals. No significant difference was found in postoperative morbidities by Clavien-Dindo classification. There was no mortality reported in both groups of the enrolled hospitals. CONCLUSIONS: Hospital volume is not a decisive factor in affecting postoperative morbidity and mortality for well-trained beginners in laparoscopic surgery for gastric cancer.

The value of N staging with the positive lymph node ratio, and splenectomy, for remnant gastric cancer: A multicenter retrospective study.

BACKGROUND: Surgery for remnant gastric cancer (RGC) frequently fails to obtain the >15 lymph nodes necessary for tumor-node-metastasis (TNM) staging. We aimed to evaluate the utility of the recently developed tumor-ratio-metastasis (TRM) staging system. We also examined the pattern of lymph node metastasis and the role of prophylactic splenectomy in RGC. METHODS: Between May 2003 and December 2012, data from 170 patients who underwent surgery for RGC were retrospectively analyzed. RESULTS: RGC arising after previous benign disease (n = 46) was associated with retrieval of more lymph nodes (27.3 vs 10.0; P < 0.001), and a lower rate of retrieving ≤15 lymph nodes (15.6% vs 77.4%, P < 0.001), than after previous malignant disease (n = 122). The 5 year survival rate according to TNM staging was 75% in stage I, 77.1% in stage II, and 23.5% in stage III, whereas by TRM staging it was 75%, 81.6%, and 23.2%, respectively. Overall survival was not different between the splenectomy and non-splenectomy groups at each stage (P = 0.751, 0.723, 0.151, and 0.706 for stage I, II, III, and IV, respectively). CONCLUSION: The analyses did not identify a survival benefit from prophylactic splenectomy or show an improvement in staging with the TRM system for RGC.

Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas.

OBJECTIVE: The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas. BACKGROUND: Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis. METHODS: One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro. Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts. RESULTS: Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (P = 0.045), large tumor size (P = 0.007), higher T category (P < 0.001), and the presence of perineural invasion (P = 0.018). Patients with stroma-rich SRC carcinomas had a significantly shorter disease-free survival (P < 0.001) and overall survival (P < 0.001). However, in a subgroup analysis, the prognostic significance of the stromal proportion correlated only with patients with T3/4 disease. From multivariate analysis, the high stromal proportion is an independent prognostic factor to predict worse disease-free survival (hazard ratio 2.288; P = 0.001) and overall survival (hazard ratio 2.503; P = 0.001). We found that CAFs enhanced the migratory abilities of cancer cells through the epithelial-mesenchymal transition, and RNA sequencing results confirmed these findings. CONCLUSIONS: The intratumor stromal proportion could be a useful prognostic biomarker and a potential therapeutic target in gastric SRC carcinomas.

Modified overlap method using knotless barbed sutures (MOBS) for intracorporeal esophagojejunostomy after totally laparoscopic gastrectomy.

BACKGROUND: Compared to end-to-side anastomosis with a circular stapler, the overlap method is favored for intracorporeal esophagojejunostomy because it facilitates handling of the stapler, even in narrow spaces, and wider anastomosis. However, it associates with technical difficulties during anastomosis, including difficult traction on the esophageal stump that necessitates stay sutures. Here, we introduce a new modified overlap method that employs knotless barbed sutures (MOBS) and report the outcomes of our case series. METHOD: All consecutive patients who underwent intracorporeal esophagojejunostomy in 2015-2016 were included. All patients underwent surgery as follows: After esophageal transection with a linear stapler, two V-loc 90 sutures (Covidien, Mansfield, MA, USA) were sutured in the center of the stapled line. The opening was made between the two threads, and the intraluminal space was identified. The jejunum was ascended toward the esophageal stump by inserting a 45-mm-long linear staple. The anastomosis was made at the space between the right and left crura. After firing the linear stapler, the entry hole was closed bidirectionally using the pre-sutured threads. RESULTS: Forty patients underwent MOBS (27 by laparoscopy; 13 by robot). Mean total operative and MOBS procedural times were 180.6 and 22.4 min, respectively. Mean hospital stay was 6.9 days. Two patients had major complications (5.0 %). There were no anastomosis-related complications. Laparoscopy and robot subgroups did not differ in mean MOBS procedural times (22.2 vs. 22.7 min, p = 0.787). CONCLUSION: MOBS is a safe and feasible method that is a good option for intracorporeal esophagojejunostomy after laparoscopic gastrectomy.

The learning curve associated with laparoscopic total gastrectomy.

BACKGROUND: Although the frequency of laparoscopic total gastrectomy (LTG) has been increasing, the procedure requires considerable experience because of its technical difficulty and the concern for oncological safety. This study intended to define the learning curve associated with the procedure. METHODS: All 256 cases of LTG performed from June 2003 to December 2012 were enrolled. The cases were divided into ten groups of 25 cases based on when they occurred. The learning curve was defined using the moving average method. LTG, performed in the absence of other procedures (pure-LTG, 132 cases), was extracted from the ten groups, and the mean operative time and estimated blood loss (EBL) were compared to define the learning curve. Retrieved lymph nodes, hospital stay, and complications were compared across the phases of the learning curve. LTG with spleen resection, performed in the absence of other procedures (pure-srLTG, 53 cases), was also analyzed by the same method. RESULTS: A three-phase learning curve of LTG was defined: the first two groups, the following two groups, and the final six groups (mean operative time: 223.0, 244.8, and 207.8 min, respectively, p = 0.003; mean EBL: 94.6, 237.0, and 116.5 ml, respectively, p < 0.001). The rates of complications and open conversions were similar across the three phases. There were no significant differences in mean operative time, EBL, retrieved LNs, hospital stay, or complication rates between pure-LTG and pure-srLTG, after completing the respective learning curves. CONCLUSIONS: Experience with approximately 100 LTG cases was required to complete learning of the procedure.

Linear-shaped gastroduodenostomy (LSGD): safe and feasible technique of intracorporeal Billroth I anastomosis.

BACKGROUND: Although delta-shaped gastroduodenostomy (DSGD) is used increasingly as an intracorporeal Billroth I anastomosis after distal gastrectomy, worries about anatomical distortion always exist in twisting stomach and making an oblique incision on duodenum. We developed a new method of intracorporeal gastroduodenostomy, the linear-shaped gastroduodenostomy (LSGD), in which anastomosis is done using endoscopic linear staplers only without any complicated rotation. In this report, we introduced LSGD and compared its short-term and long-term outcomes with DSGD. METHODS: We analyzed 261 consecutive gastric cancer patients who underwent the intracorporeal gastroduodenostomy between January 2009 and May 2014 (LSGD: 190, DSGD: 71), retrospectively. All of them underwent a laparoscopic or robotic distal gastrectomy with regional lymph node dissection. Early surgical outcomes such as operation time, postoperative complications, days until soft diet began, length of hospital stay, and endoscopic findings in postoperative 6 and 12 months were evaluated. RESULTS: Although the proportion of robotic approach and D2 lymphadenectomy were significantly higher in LSGD group, the rates for overall complications (13.2 % [LSGD] vs. 9.9 % [DSGD], p = 0.470) and major complications (5.8 vs. 5.6 %, p = 1.0) were similar between two groups. There were no differences in anastomotic bleeding (1.1 vs. 1.4 %, p = 1.0), stenosis (3.2 vs. 2.8 %, p = 1.0), and leakage (0.5 vs. 0.0 %, p = 1.0). Endoscopy performed 6 months postoperatively showed that residual food (p = 0.022), gastritis (p = 0.018), and bile reflux (42.0 vs. 63.2 %, p = 0.003) were significantly decreased in LSGD and there were no significant differences in postoperative 12 months. CONCLUSION: LSGD is an innovative reconstruction technique with comparable short-term outcomes to DSGD. In addition, reduced residual food, gastritis, and bile reflux were seen in LSGD.