Morbidity and Mortality After Laparoscopy-Assisted Distal Gastrectomy and Totally Laparoscopic Distal Gastrectomy to Treat Gastric Cancer: An Interim Report: A Phase III Multicenter, Prospective, Randomized Trial (The KLASS-07 Trial).

PURPOSE: We conducted a randomized prospective trial (KLASS-07 trial) to compare laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. In this interim report, we describe short-term results in terms of morbidity and mortality. METHODS AND METHODS: The sample size was 442 participants. At the time of the interim analysis, 314 patients were enrolled and randomized. After excluding patients who did not undergo planned surgeries, we performed a modified per-protocol analysis of 151 and 145 patients in the LADG and TLDG groups, respectively. RESULTS: The baseline characteristics, including comorbidity status, did not differ between the LADG and TLDG groups. Blood loss was somewhat higher in the LADG group, but statistical significance was not attained (76.76±72.63 vs. 62.91±65.68 mL; P=0.087). Neither the required transfusion level nor the operation or reconstruction time differed between the 2 groups. The mini-laparotomy incision in the LADG group was significantly longer than the extended umbilical incision required for specimen removal in the TLDG group (4.79±0.82 vs. 3.89±0.83 cm; P<0.001). There were no between-group differences in the time to solid food intake, hospital stay, pain score, or complications within 30 days postoperatively. No mortality was observed in either group. CONCLUSIONS: Short-term morbidity and mortality rates did not differ between the LADG and TLDG groups. The KLASS-07 trial is currently underway. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03393182.

Feasibility of Regional Lymphadenectomy for Stomach-Preserving Surgery in Early Gastric Cancer Omitting Sentinel Node Navigation: A Post Hoc Analysis of the SENORITA Trial.

BACKGROUND: Sentinel node navigation (SNN) has been known as the effective treatment for stomach-preserving surgery in early gastric cancer; however, SNN presents several technical difficulties in real practice. OBJECTIVE: This study aimed to evaluate the feasibility of regional lymphadenectomy omitting SNN, using the post hoc analysis of a randomized controlled trial. METHODS: Using data from the SENORITA trial that compared laparoscopic standard gastrectomy with lymphadenectomy and laparoscopic SNN, 237 patients who underwent SNN were included in this study. Tumor location was divided into longitudinal and circumferential directions. According to the location of the tumor, the presence or absence of lymph node (LN) metastases between sentinel and non-sentinel basins were analyzed. Proposed regional LN stations were defined as the closest area to the primary tumor. Sensitivities, specificities, positive predictive values, and negative predictive values (NPV) of SNN and regional lymphadenectomy were compared. RESULTS: Metastasis to non-sentinel basins with tumor-free in sentinel basins was observed in one patient (0.4%). The rate of LN metastasis to non-regional LN stations without regional LN metastasis was 2.5% (6/237). The sensitivity and NPV of SNN were found to be significantly higher than those of regional lymphadenectomy (96.8% vs. 80.6% [p = 0.016] and 99.5% vs. 97.2% [p = 0.021], respectively). CONCLUSIONS: This study showed that regional lymphadenectomy for stomach-preserving surgery, omitting SNN, was insufficient; therefore, SNN is required in stomach-preserving surgery.

A predictive model using MRI and clinicopathologic features for breast cancer recurrence in young women treated with upfront surgery.

OBJECTIVES: To identify preoperative breast MR imaging and clinicopathological variables related to recurrence and develop a risk prediction model for recurrence in young women with breast cancer treated with upfront surgery. METHODS: This retrospective study analyzed 438 consecutive women with breast cancer aged 35 years or younger between January 2007 and December 2016. Breast MR images before surgery were independently reviewed by breast radiologists blinded to patient outcomes. The clinicopathological data including patient demographics, clinical features, and tumor characteristics were reviewed. Univariate and multivariate logistic regression analyses were used to identify the independent factors associated with recurrence. The risk prediction model for recurrence was developed, and the discrimination and calibration abilities were assessed. RESULTS: Of 438 patients, 95 (21.7%) developed recurrence after a median follow-up of 65 months. Tumor size at MR imaging (HR = 1.158, p = 0.006), multifocal or multicentric disease (HR = 1.676, p = 0.017), and peritumoral edema on T2WI (HR = 2.166, p = 0.001) were identified as independent predictors of recurrence, while adjuvant endocrine therapy (HR = 0.624, p = 0.035) was inversely associated with recurrence. The prediction model showed good discrimination ability in predicting 5-year recurrence (C index, 0.707 in the development cohort; 0.686 in the validation cohort) and overall recurrence (C index, 0.699 in the development cohort; 0.678 in the validation cohort). The calibration plot demonstrated an excellent correlation (concordance correlation coefficient, 0.903). CONCLUSION: A prediction model based on breast MR imaging and clinicopathological features showed good discrimination to predict recurrence in young women with breast cancer treated with upfront surgery, which could contribute to individualized risk stratification. CLINICAL RELEVANCE STATEMENT: Our prediction model, incorporating preoperative breast MR imaging and clinicopathological features, predicts recurrence in young women with breast cancer undergoing upfront surgery, facilitating personalized risk stratification and informing tailored management strategies. KEY POINTS: Younger women with breast cancer have worse outcomes than those diagnosed at more typical ages. The described prediction model showed good discrimination performance in predicting 5-year and overall recurrence. Incorporating better risk stratification tools in this population may help improve outcomes.

Totally laparoscopic versus laparoscopy-assisted distal gastrectomy: the KLASS-07: a randomized controlled trial.

BACKGROUNDS: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). The authors performed an RCT to confirm if TLDG is different from LADG. METHODS: The KLASS-07 trial is a multi-centre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enroled from 21 cancer care centres in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was quality of life (QoL) for 1 year. This trial is registered at ClinicalTrials.gov (NCT03393182). RESULTS: Four hundred forty-two patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P= 0.006; and 0.5% vs. 4.3%, P= 0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P< 0.05). However, these QoL differences were resolved at 1 year. CONCLUSIONS: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complications but has the advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months.

JOURNAL/ijos/04.03/01279778-202408000-00031/figure1/v/2024-08-13T152924Z/r/image-jpeg.

Quality of Life and Nutritional Outcomes of Stomach-Preserving Surgery for Early Gastric Cancer: A Secondary Analysis of the SENORITA Randomized Clinical Trial.

Importance: The Sentinel Node Oriented Tailored Approach (SENORITA) randomized clinical trial evaluated quality of life (QoL) and nutritional outcomes between the laparoscopic sentinel node navigation surgery (LSNNS) and laparoscopic standard gastrectomy (LSG). However, there has been no report on the QoL and nutritional outcomes of patients who underwent stomach-preserving surgery among the LSNNS group. Objective: To compare long-term QoL and nutritional outcomes between patients who underwent stomach-preserving surgery and those who underwent standard gastrectomy and to identify factors associated with poor QoL outcomes in patients who underwent stomach-preserving surgery. Design, Setting, and Participants: This study is a secondary analysis of the SENORITA trial, a randomized clinical trial comparing LSNNS with LSG. Patients from 7 tertiary or general hospitals across the Republic of Korea were enrolled from March 2013 to December 2016, with follow-up through 5 years. Data were analyzed between August and September 2022. Among trial participants, patients who underwent actual laparoscopic standard gastrectomy in the LSG group and those who underwent stomach-preserving surgery in the LSNNS group were included. Patients who did not complete the baseline or any follow-up questionnaire were excluded. Intervention: Stomach-preserving surgery vs standard gastrectomy. Main Outcomes and Measures: Overall European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30) and stomach module (STO22) scores, body mass index, hemoglobin, protein, and albumin levels. Results: A total of 194 and 257 patients who underwent stomach-preserving surgery and standard gastrectomy, respectively, were included in this study (mean [SD] age, 55.6 [10.6] years; 249 [55.2%] male). The stomach-preserving group had better QoL scores at 3 months postoperatively in terms of physical function (87.2 vs 83.9), dyspnea (5.9 vs 11.2), appetite loss (13.1 vs 19.4), dysphagia (8.0 vs 12.7), eating restriction (10.9 vs 18.2), anxiety (29.0 vs 35.2), taste change (7.4 vs 13.0), and body image (19.5 vs 27.2). At 1 year postoperatively, the stomach-preserving group had significantly higher body mass index (23.9 vs 22.1, calculated as weight in kilograms divided by height in meters squared) and hemoglobin (14.3 vs 13.3 g/dL), albumin (4.3 vs 4.25 g/dL), and protein (7.3 vs 7.1 g/dL) levels compared to the standard group. Multivariable analyses showed that tumor location (greater curvature, lower third) was favorably associated with global health status (ß, 10.5; 95% CI, 3.2 to 17.8), reflux (ß, -8.4; 95% CI, -14.7 to -2.1), and eating restriction (ß, -5.7; 95% CI, -10.3 to -1.0) at 3 months postoperatively in the stomach-preserving group. Segmental resection was associated with risk of diarrhea (ß, 40.6; 95% CI, 3.1 to 78.1) and eating restriction (ß, 15.1; 95% CI, 1.1 to 29.1) at 3 years postoperatively. Conclusions and Relevance: Stomach-preserving surgery after sentinel node evaluation was associated with better long-term QoL and nutritional outcomes than standard gastrectomy. These findings may help facilitate decision-making regarding treatment for patients with early-stage gastric cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT01804998.

Clinical Efficacy of Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer: 5-year Results of the SENORITA Trial.

OBJECTIVE: This study aimed to compare laparoscopic standard gastrectomy (LSG) and laparoscopic sentinel node navigation surgery (LSNNS) for EGC in terms of 5-year long-term oncologic outcomes. SUMMARY BACKGROUND DATA: The oncological safety of LSNNS for early gastric cancer (EGC) has not been confirmed. Three-year disease-free survival (DFS), which is the primary endpoint of the phase III multicenter randomized controlled clinical trial (SEntinel Node ORIented Tailored Approach [SENORITA] trial), did not show the non-inferiority of LSNNS relative to LSG. METHODS: The SENORITA trial, a multicenter randomized clinical trial, was designed to show that LSNNS is non-inferior to LSG in terms of 3-year DFS. In the present study, we collected 5-year follow-up data from 527 patients recruited in the SENORITA trial as the full analysis set (FAS). Disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and recurrence patterns were evaluated using the FAS of both LSG (n=269) and LSNNS (n=258). RESULTS: The 5-year DFS was not significantly different between the LSG and LSNNS groups (P=0.0561). During the 5-year follow-up, gastric cancer-related events, such as metachronous cancer, were more frequent in the LSNNS group than in the LSG group. However, ten recurrent cancers in the remnant stomach of both groups were curatively resected by additional gastrectomy and one by additional endoscopic resection. Two of the 198 patients who underwent local resection for stomach preservation based on the LSNNS results developed distant metastasis. However, there was no statistically significant difference in the 5-year OS and DSS (P=0.7403 and P=0.9586, respectively) between the two groups. CONCLUSION: The 5-year DFS, DSS and OS did not differ significantly between the two groups. Considering the benefits of LSNNS on postoperative quality of life, LSNNS could be recommended as an alternative treatment option for EGC.

Reappraisal of optimal reconstruction after distal gastrectomy - a study based on the KLASS-07 database.

BACKGROUNDS: This study aimed to compare the incidence of bile reflux, quality of life (QoL), and nutritional status among Billroth II (BII), Billroth II with Braun anastomosis (BII-B), and Roux-en-Y (RY) reconstruction after laparoscopic distal gastrectomy (LDG). MATERIALS AND METHODS: We reviewed the prospective data of 397 patients from a multicentre database who underwent LDG for gastric cancer between 2018 and 2020 at 20 tertiary teaching hospitals in Korea. Postoperative endoscopic findings, QoL surveys using the European Organization for Research and Treatment of Cancer questionnaire (C30 and STO22), and nutritional and surgical outcomes were compared among groups. RESULTS: In endoscopic findings, bile reflux was the lowest in the RY group ( n =67), followed by the BII-B ( n =183) and BII groups ( n =147) at 1 year (3.0 vs. 67.8 vs. 84.4%, all P <0.05). The anti-reflux capability of BII-B was statistically better than that of BII, but not as perfect as that of RY. From the perspective of QoL, BII-B was not inferior to RY, but better than BII reconstruction in causing fewer STO22 reflux symptoms at 6 and 12 months. However, only RY caused fewer C30 nausea symptoms than BII at 6 and 12 months, but not BII-B. Nutritional status and morbidities were similar among the three groups, and the operative time did not differ between the BII-B and RY groups. CONCLUSIONS: BII-B cannot substitute for RY in preventing bile reflux, shortening the operative time, or reducing morbidities. Regarding short-term QoL, BII-B was sufficient to reduce STO22 reflux symptoms but failed to reduce C30 nausea symptoms postoperatively.

The Impact of Different Types of Complications on Long-Term Survival After Total Gastrectomy for Gastric Cancer.

PURPOSE: This study aimed to investigate the impact of different types of complications on long-term survival following total gastrectomy for gastric cancer. MATERIALS AND METHODS: A total of 926 patients who underwent total gastrectomy between 2008 and 2016 were included. Patients were divided into the morbidity and no-morbidity groups, and long-term survival was compared between the 2 groups. The prognostic impact of postoperative morbidity was assessed using a multivariate Cox proportional hazard model, which accounted for other prognostic factors. In the multivariate model, the effects of each complication on survival were analyzed. RESULTS: A total of 229 patients (24.7%) developed postoperative complications. Patients with postoperative morbidity showed significantly worse overall survival (OS) (5-year, 65.0% vs. 76.7%, P<0.001) and cancer-specific survival (CSS) (5-year, 74.2% vs. 83.1%, P=0.002) compared to those without morbidity. Multivariate analysis adjusting for other prognostic factors showed that postoperative morbidity remained an independent prognostic factor for OS (hazard ratio [HR], 1.442; 95% confidence interval [CI], 1.136-1.831) and CSS (HR, 1.463; 95% CI, 1.063-2.013). There was no significant difference in survival according to the severity of complications. The following complications showed a significant association with unfavorable long-term survival: ascites (HR, 1.868 for OS, HR, 2.052 for CSS), wound complications (HR, 2.653 for OS, HR, 2.847 for CSS), and pulmonary complications (HR, 2.031 for OS, HR, 1.915 for CSS). CONCLUSIONS: Postoperative morbidity adversely impacted survival following total gastrectomy for gastric cancer. Among the different types of complications, ascites, wound complications, and pulmonary complications exhibited significant associations with long-term survival.

Erratum: Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach.

This corrects the article on p. 3 in vol. 23, PMID: 36750993.

Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach.

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer: A Randomized Clinical Trial.

PURPOSE: To compare postoperative complications, long-term survival, and quality of life (QOL) after laparoscopic sentinel node navigation surgery (LSNNS) and laparoscopic standard gastrectomy (LSG). METHODS: Five hundred eighty patients with preoperatively diagnosed stage IA gastric adenocarcinoma (≤ 3 cm) were assigned to undergo either LSG or LSNNS. Observers were not blinded to patient grouping. The primary outcome was 3-year disease-free survival (3y-DFS). Secondary outcomes included postoperative complications, QOL, 3-year disease-specific survival (3y-DSS), and 3-year overall survival (3y-OS). RESULTS: In total, 527 patients were included in the modified intention-to-treat analysis population for the primary outcome (LSG, 269; LSNNS, 258). Stomach-preserving surgery was performed in 210 patients (81%) in the LSNNS group. During the median follow-up duration, the 3y-DFS rates in the LSG and LSNNS groups were 95.5% and 91.8%, respectively (difference: 3.7%; 95% CI, -0.6 to 8.1). Three patients with recurrence and five with metachronous gastric cancer in the LSNNS group underwent standard surgery. Two patients with distant metastasis in both groups were treated with palliative chemotherapy. The 3y-DSS and 3y-OS rates in the LSG and LSNNS groups were 99.5% and 99.1% (P = .59) and 99.2% and 97.6% (P = .17), respectively. Postoperative complications occurred in 19.0% of the LSG group and 15.5% of the LSNNS group (P = .294). The LSNNS group showed better physical function (P = .015), less symptoms (P < .001), and improved nutrition than the LSG group. CONCLUSION: LSNNS did not show noninferiority to LSG for 3y-DFS, with a 5% margin. However, the 3y-DSS and 3y-OS were not different after rescue surgery in cases of recurrence/metachronous gastric cancer, and LSNNS had better long-term QOL and nutrition than LSG.

Impact of the Deep Neuromuscular Block on Oncologic Quality of Laparoscopic Surgery in Obese Gastric Cancer Patients: A Randomized Clinical Trial.

BACKGROUND: Obesity can hinder laparoscopic procedures and impede oncological safety during laparoscopic cancer surgery. Deep neuromuscular block (NMB) reportedly improves laparoscopic surgical conditions, but its oncological benefits are unclear. We aimed to evaluate whether deep NMB improves the oncologic quality of laparoscopic cancer surgery in obese patients. STUDY DESIGN: We conducted a double-blinded, parallel-group, randomized, phase 3 trial at 9 institutions in Korea. Clinical stage I and II gastric cancer patients with a BMI at or above 25 kg m -2 were eligible and randomized 1:1 ratio to the deep or moderate NMB groups, with continuous infusion of rocuronium (0.5-1.0 and 0.1-0.5 mg kg -1 h -1, respectively). The primary endpoint was the number of retrieved lymph nodes (LNs). The secondary endpoints included the surgeon's surgical rating score (SRS) and interrupted events. RESULTS: Between August 2017 and July 2020, 196 patients were enrolled. Fifteen patients were excluded, and 181 patients were finally included in the study. There was no significant difference in the number of retrieved LNs between the deep (N = 88) and moderate NMB groups (N = 93; 44.6 ± 17.5 vs 41.5 ± 16.9, p = 0.239). However, deep NMB enabled retrieving more LNs in patients with a BMI at or above 28 kg/m2 than moderate NMB (49.2 ± 18.6 vs 39.2 ± 13.3, p = 0.026). Interrupted events during surgery were lower in the deep NMB group than in the moderate NMB group (21.6% vs 36.6%; p = 0.034). The SRS was not influenced by NMB depth. CONCLUSION: Deep NMB provides potential oncologic benefits by retrieving more LNs in patients with BMI at or above 28 kg/m2 during laparoscopic gastrectomy.

Prognostic Value of the Anatomic Region of Metastatic Lymph Nodes in the Current TNM Staging of Gastric Cancer.

PURPOSE: The numeric N stage has replaced the topographic N stage in the current tumor node metastasis (TNM) staging in gastric carcinoma. However, the usefulness of the topographic N stage in the current TNM staging system is uncertain. We aimed to investigate the prognostic value of the topographic N stage in the current TNM staging system. MATERIALS AND METHODS: We reviewed the data of 3350 patients with gastric cancer who underwent curative gastrectomy. The anatomic regions of the metastatic lymph nodes (MLNs) were classified into 2 groups: perigastric and extra-perigastric. The prognostic value of the anatomic region was analyzed using a multivariate prognostic model with adjustments for the TNM stage. RESULTS: In patients with lymph node metastasis, extra-perigastric metastasis demonstrated significantly worse survival than perigastric metastasis alone (5-year survival rate, 39.6% vs. 73.1%, respectively, P<0.001). Extra-perigastric metastasis demonstrated significantly worse survival within the same pN stage; the multivariate analysis indicated that extra-perigastric metastasis was an independent poor prognostic factor (hazard ratio=1.33; 95% confidence interval=1.01-1.75). The anatomic region of the MLNs improved the goodness-of-fit (likelihood ratio statistics, 4.57; P=0.033) of the prognostic model using the TNM stage. CONCLUSIONS: The anatomic region of MLNs has an independent prognostic value in the numeric N stage in the current TNM staging of gastric carcinoma.

Treatment Modality Based Survival in Gastric Carcinoma Patients with Stand-Alone Peritoneal Metastasis: a Case-Control Study.

PURPOSE: To date, there are no promising treatments for gastric carcinoma with peritoneal metastasis. Some researchers have suggested a survival benefit of gastrectomy in select patients. This study investigated the survival of gastric carcinoma patients with stand-alone peritoneal metastasis according to the type of treatment modality. MATERIALS AND METHODS: We reviewed the data of 132 patients with gastric carcinoma and stand-alone peritoneal metastasis. We performed gastrectomy when the primary tumor was deemed resectable and systemic chemotherapy was administered. We analyzed patient survival according to the type of treatment, and the prognostic value of gastrectomy was evaluated in univariate and multivariate models. RESULTS: Among all patients, 70 underwent gastrectomy plus chemotherapy, 20 underwent gastrectomy alone, 36 underwent chemotherapy alone, and 6 received supportive care. The median patient survival was 13 months. Patients who underwent gastrectomy had significantly longer survival than those who did not undergo gastrectomy (14 vs. 8 months, P<0.001). Patients who received chemotherapy showed significantly longer survival than those who did not (13 vs. 7 months, P=0.032). Patients who underwent gastrectomy plus chemotherapy showed better survival than those who underwent other treatments. In multivariate analysis, gastrectomy was found to be an independent prognostic factor (hazard ratio, 0.52; 95% confidence interval, 0.33-0.82) in addition to chemotherapy. CONCLUSIONS: Our study showed that patients who underwent gastrectomy plus chemotherapy had the best survival. Although the survival benefit of gastrectomy remains uncertain, it is a favorable prognostic indicator in patients with stand-alone peritoneal metastasis.

PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer.

PURPOSE: Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS: Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS: Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION: PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

The benefits of enhanced recovery after surgery for gastric cancer: A large before-and-after propensity score matching study.

BACKGROUND & AIMS: The benefits of enhanced recovery after surgery (ERAS) in patients undergoing gastrectomy have been reported in several studies; however, there is limited evidence supporting the efficacy of ERAS in clinical settings. We aimed to identify the benefits of ERAS in the clinical setting by investigating short-term surgical outcomes before and after the implementation of ERAS in patients who underwent gastrectomy. METHODS: We searched our gastric cancer database from 2008 to 2018 to identify patients who underwent gastrectomy before ERAS was implemented (2008-2009) and after the final version of ERAS was implemented (2016-2018). We enrolled 424 patients who were treated before ERAS was implemented and 565 patients who received our completed version of ERAS. After propensity score matching, each group included 219 patients, and short-term surgical outcomes were compared between the two groups. RESULTS: The length of hospital stay was significantly shorter in the ERAS group (8.8 vs. 11.5 days, p = 0.001), but the readmission rates were similar in the two groups, at 2.3%. There were no significant differences in morbidity, mortality, and complications of ≥ grade III between the groups. Of the complications, intra-abdominal bleeding (0% vs. 4.1%, p = 0.002) and intra-abdominal abscess (0% vs. 2.7%, p = 0.038) were significantly lower, whereas postoperative ileus was significantly higher in the ERAS group (8.6% vs. 0.5%, p < 0.001). In subgroup analyses by age, operative approach, and the extent of gastric resection, the ERAS group experienced a shorter hospital stay without increased readmission in all subgroups. CONCLUSIONS: These results demonstrated that ERAS was associated with a 3-day reduction in hospital stay without increased readmission after gastrectomy. This study validated the benefits of ERAS in the clinical setting of gastrectomy.

Comparison of long term survival outcomes between D1+ and D2 lymph node dissection for ≥ pT2 or pN+ gastric carcinoma: A large scale case-control study using propensity score matching.

BACKGROUND: D2 lymph node dissection (LND) is a widely performed as a standard procedure for advanced gastric cancer (AGC). However, there is little evidence supporting D2 over D1+ LND for gastric cancer treatment. This study compared the long-term outcomes of D2 and D1+ LND for AGC. METHODS: We retrospectively reviewed data on 1121 patients who underwent curative distal gastrectomy and had pathologic stage of ≥ pT2 or pN+. The patients were categorized into the D1+ and D2 LND groups, and long-term survival was compared in the original and propensity score matching (PSM) cohorts. RESULTS: Overall, 909 and 212 patients underwent D2 and D1+ LND, respectively. The D2 group showed more advanced stage and more frequently underwent open surgery. Postoperative morbidity was significantly higher in the D2 group (19.5% vs. 13.2%, p = 0.034); however, mortality or ≥ grade III complications did not significantly differ between the groups. The 5-year overall survival (OS) and disease-free survival (DFS) did not significantly differ between D2 and D1+ groups at the same stage. Multivariate analysis of prognostic factors revealed that the extent of LND did not significantly affect survival, after adjusting for tumor stage and other clinicopathological factors. In the PSM cohort, the D2 and D1 groups showed no significant difference in OS (p = 0.488) and DFS (p = 0.705). CONCLUSIONS: Long-term survival with D1+ LND was comparable to that with D2 LND for ≥ pT2 or pN + gastric carcinoma. A large randomized trial is warranted to validate the optimal extent of LND for gastric carcinoma.

Reduced anastomotic complications with intracorporeal esophagojejunostomy using endoscopic linear staplers (overlap method) in laparoscopic total gastrectomy for gastric carcinoma.

BACKGROUND: With advances in surgical technique and instrumentation, intracorporeal anastomosis is increasingly being performed for laparoscopic total gastrectomy (LTG). However, the benefits of intracorporeal anastomosis in reducing postoperative complications have not been demonstrated, although its technical feasibility has been proven in many studies. In this study, we investigated the impact of intracorporeal anastomosis in reducing postoperative complications after LTG. METHODS: We analyzed 410 consecutive gastric cancer patients who underwent LTG between 2008 and 2018. Of these, 118 underwent intracorporeal anastomosis using linear staplers (overlap method), while 292 underwent extracorporeal anastomosis using a circular stapler. Short-term surgical outcomes including postoperative complications were compared between the two groups. RESULTS: The two groups showed no significant differences in age, sex, comorbidity, and abdominal surgery history. D2 lymph node dissection was more frequently performed in the intracorporeal group because of the presence of more advanced cancer stages. The overall morbidity in the intracorporeal and extracorporeal group was 23.7% and 27.7%, respectively (p = 0.405). However, the intracorporeal group showed a significantly lower incidence of late complications (0.8% vs. 7.5%, p = 0.008). Concerning complications, the incidence of anastomotic bleeding (0% vs. 5.5%, p = 0.008) and anastomotic stenosis (0% vs. 4.5%, p = 0.024) was significantly lower in the intracorporeal group. In univariate and multivariate analyses, American Society of Anesthesiologists score and operative bleeding were independent predictive factors for postoperative complications in patients who underwent intracorporeal anastomosis. CONCLUSIONS: Intracorporeal anastomosis using linear staplers reduced anastomotic bleeding and stenosis compared to extracorporeal anastomosis after LTG. Future research will be required to determine the ideal method for intracorporeal anastomosis in LTG.

Prognostic Performance of Preoperative Staging: Assessed by Using Multidetector Computed Tomography-Between the New Clinical Classification and the Pathological Classification in the Eighth American Joint Committee on Cancer Classification for Gastric Carcinoma.

BACKGROUND: Since the eighth American Joint Committee on Cancer (AJCC) classification recently introduced the clinical classification for preoperative staging of gastric cancer, the new clinical classification has not been extensively validated yet. Therefore, in this study, we compared the prognostic performance of the new clinical classification and the pathologic classification for preoperative staging of gastric cancer. METHODS: We reviewed 3027 patients with gastric cancer who were surgically treated between 2009 and 2013. Patient survival was analyzed according to the preoperative stage by the clinical classification and the pathologic classification in the eighth AJCC classification. The prognostic performance was examined using the Akaike information criterion (AIC) value and Harrell c-index. RESULTS: Patient survival was significantly different across the different stages when both classifications were used. However, individual pairwise comparisons showed that survival differences between each stage were more distinctive and homogeneous in the pathologic classification. In the multivariate model adjusted for the final pathologic stage, preoperative staging by the pathologic classification was an independent prognostic factor, whereas the clinical classification was not. The pathologic classification showed a lower AIC value compared with the clinical classification (5100.64 vs. 5114.14). The Harrell c-index was higher in the pathologic classification than in the clinical classification (0.741 vs. 0.739). CONCLUSIONS: The new clinical classification in the eighth AJCC classification discriminates patient survival well. However, it does not appear to have a better prognostic performance compared with the pathologic classification for preoperative staging of gastric cancer.