D2 Gastrectomy Research Articles

Oxaliplatin and capecitabine (XELOX) plus toripalimab as perioperative treatment for locally advanced gastric or gastro-esophageal junction adenocarcinoma (Neo-Capture): A single-arm, phase 2 study.

e16001 Background: PD-1 inhibitor combined with chemotherapy showed remarkable objective response rate in the first line treatment of metastatic gastric cancer. While, the benefit of perioperative PD-1 inhibitor plus chemotherapy in locally advanced gastric or gastro-esophageal junction (G/GEJ) cancer was not clear. Therefore, we aimed to assess the efficacy and safety of perioperative XELOX plus toripalimab in the patients with locally advanced G/GEJ cancer in this study. Methods: This was a prospective single arm phase 2 study. Eligible patients were with histologically confirmed locally advanced G/GEJ (Siewert II/II type) adenocarcinoma (cT3-4 Nany M0 or T1-2 N2-3 M0). Patients received 4 preoperative and 2 postoperative cycles of XELOX plus toripalimab (oxaliplatin 130mg/m2 D1, capecitabine 1000mg/m2 bid D1-14, toripalimab 240mg D1, Q3W) followed by subsequent 2 cycles of toripalimab monotherapy. Patients underwent D2 gastrectomy after preoperative treatment. The primary endpoint was major pathological response (MPR) according to Becker TRG criteria. Secondary endpoints included safety, R0 resection rate, pathological complete response (pCR), 3-year disease free survival (DFS) and 3-year overall survival (OS). Results: From Jul, 2019, to Dec, 2021, 35 pts were recruited. The median age was 61 (34-72) years old. 80% of the pts were men. Acutally, all the pts had cT4 (cT4a [48.6%] & cT4b [51.4%]) and 88.6% had cN+ by CT, MRI and ultrasound gastroscopy. 2 pts suffered disease progression during neoadjuvant treatment. 4 pts have not yet completed preoperative therapy. 29 pts had received gastrectomy and 2 pts were pathologically diagnosed with large cell neuroendocrine carcinoma. Therefore, 27 adenocarcinoma pts were included in this analysis. 3 (11.1%) pts achieved pCR (TRG1a) and 4 (14.8%) pts achieved MPR (TRG1a/b). R0 resection was achieved in 96.3% (26/27) of the pts. No patient had pT4b. The most common (≥10%) grade 1-2 treatment related adverse events (TRAEs) included leucopenia (45.7%), neutropenia (42.9%), thrombocytopenia (20%), nausea (34.1%), vomiting (14.3%), anorexia (14.3%), ALT increased (40%) and AST increased (34.3%). Only 4 (11.4%) pts experienced grade 3 neutropenia. No other ≥ grade 3 TRAEs occurred. Most of the potential immune-related adverse events were grade 1-2 including hypothyroidism (8.6%), adrenal insufficiency (2.9%) and hyperglycemia (11.4%). Only one (2.9%) patient had grade 3 hyperglycemia. No serious perioperative complication and death occurred. Conclusions: Perioperative XELOX plus toripalimab preliminarily showed a favorable R0 resection rate and acceptable MPR in cT4a/T4b locally advanced G/GEJ cancer patients with a manageable safety profile. Clinical trial information: NCT04119622.

A randomized, controlled, multi-center, open-label study of adjuvant nab-paclitaxel plus S-1 (AS) versus capecitabine plus oxaliplatin (CapeOX) for stage III gastric cancer after D2 resection.

4052 Background: There was no prospective randomized study compared taxanes plus fluoropyrimidine versus platinum plus fluoropyrimidine in adjuvant chemotherapy for advanced gastric cancer. Nab-paclitaxel is nanoparticle albumin-bound formulation, showed a potentially efficacy in gastric cancer. We designed this trial to compare the effective and safety of AS and CapeOX regimen for gastric adenocarcinoma adjuvant therapy. Methods: Patients with stage III gastric or gastroesophageal junction adenocarcinoma who had D2 surgery and achieved R0 resection were randomized 1:1 to AS group and CapeOX. Randomization was stratified by differentiation type (differentiated vs. undifferentiated) and AJCC/UICC pathological stage (IIIA vs. IIIB, IIIC). AS group: Nab-paclitaxel 100 mg/m2 on d1 and d8; S-1 80-120mg/d, p.o., bid on d1-d14; repeated every 21 days for 8 cycles. CapeOX group: oxaliplatin 130 mg/m2 on d1; capecitabine 1000 mg/m2, p.o., bid on d1-d14; repeated every 21 days for 8 cycles. The primary endpoint is 3-year disease-free survival (3-year-DFS) rate, the secondary endpoints included overall survival (OS), and safety. Results: Between March, 2020 to Jan, 2022, 146 subjects were enrolled to receive either AS regimen (n = 71) or CapeOX regimen (n = 75). The baseline characteristics between two arms were generally balanced. The 1-year DFS rate was 95.50% and 72.84% in AS and CapeOX group, respectively. At the cutoff date, 3 patients (the recurrence sites were peritoneum [n = 1], locoregional [n = 1] and distant [n = 1]) in AS group had relapsed, compared with 10 patients (peritoneum [n = 2], locoregional [n = 4] and distant [n = 4]) in CapeOX group. 4 subjects in CapeOX group died compared with 0 in AS group. A total of 42 patients (AS, n = 21 [29.58%]; CapeOX, n = 21 [28.00%]) needed dose reduction main due to hematological toxicity. The median relative dose intensity of Nab-paclitaxel, S-1, oxaliplatin and capecitabine was 82.55%, 91.30%%, 83.16%% and 78.95%, respectively. Treatments were delayed in 82 of 297 (27.61%, 24 due to hematological and 15 due to non-hematological toxicity) cycles at AS group and in 100 of 319 (31.35%, 18 due to hematological and 13 due to non-hematological toxicity) cycles at CapeOX group. There were 34 (47.89%) patients in AS group and 30 (40.00%) patients in CapeOX group occurred treatment-related adverse events (TRAEs), though most of them were grade I-II. Main grade III-IV AEs were neutropenia (28.16% in AS group vs 8.00% in CapeOX group), leucopenia (15.49% vs 1.33%), thrombocytopenia (0% vs 8.00%) and anemia (5.63% vs 1.33%). Conclusions: Adjuvant AS regimen showed a trend towards better DFS compared with CapeOX regimen, and is a potentially regimen for stage III gastric cancer after curative D2 gastrectomy, with tolerable toxicity. Long-term survival benefit requires more data. Clinical trial information: NCT04135781.

Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): An open-label, randomized, phase 2 study.

4031 Background: The optimal perioperative chemotherapy of locally advanced gastric or gastro-esophageal junction (G/GEJ) cancer has not been established in Asia, though FLOT was considered as standard therapy in Europe. Therefore, we aimed to assess efficacy and safety of DOS versus SOX as perioperative treatment in patients with locally advanced G/GEJ cancer in this study. Methods: This was a single center, open-label, randomized, phase 2 study. Eligible pts were aged ≥18 years with histologically diagnosed HER2 negative cT3-4 Nany M0 G/GEJ (Siewert II/III type) adenocarcinoma. Pts were randomized (1:1) to receive either 4 preoperative and 4 postoperative cycles of DOS (docetaxel 60mg/m2 D1, oxaliplatin 100mg/m2 D1, S-1 40-60mg bid D1-14 depending on body surface area (BSA), Q3W) or SOX (oxaliplatin 130mg/m2 D1, S-1 40-60mg bid D1-14 depending on BSA, Q3W). Pts underwent D2 gastrectomy after preoperative treatment. The primary endpoint was major pathological response (MPR) analyzed in the modified intention to treat (mITT) population according to Becker TRG criteria. Secondary endpoints included the 3-year progression free survival (PFS), the 3-year overall survival (OS), pathological complete response, R0 resection rate and safety. Results: From Aug, 2015, to Dec, 2019, 154 pts were enrolled, 7 pts withdrew consent, 147 pts were included as mITT population (DOS 71; SOX 76). 80.3% and 67.1% of the pts in the DOS and SOX groups accepted surgery respectively. More pts achieved MPR (25.4% vs. 11.8%, p = 0.035) and R0 resection (78.9% vs. 61.8%, p = 0.024) in the DOS group than the SOX group. With a median follow-up of 42.4 months, the 3-year PFS and the 3-year OS were 52.3% vs. 35% (p = 0.065, HR 0.667, 95%CI 0.432-1.029) and 57.5% vs. 49.2% (p = 0.114, HR 0.685, 95%CI 0.429-1.095) in the DOS and SOX groups, respectively. Pts who acquired MPR had a significant longer survival than non-MPR pts. The 3-year PFS were 89.4% vs. 38.6% (p < 0.001, HR 0.076, 95%CI 0.018-0.314). The 3-year OS were 100% vs. 50.1% (p = 0.008, HR 0.024, 95%CI 0.002-0.371). 56.1% and 60.8% of the pts completed at least 6 cycles of the perioperative chemotherapy in the DOS and SOX groups, respectively (p = 0.625). The most common grade ≥3 TRAEs included neutropenia (8.5% vs.10.5%), leucopenia (1.4% vs. 5.3%), thrombocytopenia (1.4% vs 15.8%, p = 0.002), anemia (1.4% vs. 3.9%) and diarrhea (1.4% vs. 2.6%). The incidence of grade 1-2 thrombocytopenia was also significant lower in the DOS group (15.5% vs. 31.6%, p = 0.022). No treatment-related deaths occurred. Conclusions: Perioperative DOS improved MPR significantly and tended to have better PFS compared with SOX in locally advanced G/GEJ cancer, might be regarded as a prefered option of perioperative chemotherapy. Clinical trial information: NCT02725424.

Surgical and oncological outcomes of D1 versus D2 gastrectomy among elderly patients treated for gastric cancer.

Gastrectomy with D2 lymphadenectomy is considered standard treatment in gastric cancer (GC). Among Western patients, morbidity and mortality seem to increase in D2 relative to D1 lymphadenectomy. As elderly patients with co-morbidities are more prone to possible complications, it is unclear whether they benefit from D2 lymphadenectomy. This study aims to compare the short- and long-term results of D1 and D2 lymphadenectomy in elderly patients undergoing gastrectomy for GC. All elderly (⩾75 years) patients undergoing gastrectomy with curative intent for GC during 2000-2015 were included and grouped according to the level of lymph node dissection into the D1 or D2 group. Short-term surgical outcome included the Comprehensive Complication Index (CCI) and 30-day mortality. Long-term outcomes comprised overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Cox regression was used in multivariable analyses. In total, 99 elderly patients were included in the study (51 in D1 group, 48 in D2 group). The median follow-up was 32.5 months. Patients in the D1 group were older and had a higher American Society of Anesthesiologist (ASA) score. Both groups had similar burden of postoperative complications (CCI 20.9 versus 22.6, p = 0.26, respectively) and 90-day mortality (2% for both groups). The OS, DSS, and DFS were similar between groups. Multivariable analysis adjusted for potential confounders detected no difference in the survival between the D1 and D2 groups. Gastrectomy with D2 lymphadenectomy can be performed with low postoperative morbidity and mortality suggesting its use also in the elderly. Long-term outcomes seem similar but need further studies.

Adjuvant chemotherapy after curative D2 gastrectomy in Latin American patients with gastric cancer.

BackgroundGastric cancer (GC) is the fourth most common cause of cancer deaths around the world and the first cause of cancer deaths in Peru; however, there are no prospective trials for adjuvant chemotherapy in GC after curative gastrectomy in this country. The objective of this study was to evaluate the effectiveness of adjuvant chemotherapy in stage II–III gastric cancer patients who underwent D2 gastrectomy.MethodsWe included patients with stage II–III gastric cancer who underwent radical gastrectomy and D2 dissection between 2014 and 2016 at our institution. Patients received 3-week cycles of capecitabine (1,000 mg/m2 twice daily on days 1–14) plus oxaliplatin (130 mg/m2 on day 1) for 6 months. Survival curves were estimated with the Kaplan–Meier method, and the Cox proportional hazards model was used to identify prognostic factors for survival.ResultsIn total, 173 patients were included: 100 (57.8%) patients received adjuvant chemotherapy and surgery (AChS) and 73 (42.2%) surgery alone (SA). Three-year disease-free survival (DFS) was higher in the AChS groups (69%) than in the SA group (52.6%) (p = 0.034). Regarding overall survival (OS), 31 patients (31%) died in the AChS group compared with 34 (46.6%) in the SA group (p = 0.027). In the multivariate analysis, adjuvant chemotherapy was an independent prognostic factor for DFS (HR = 0.60; 95% CI = 0.37–0.97; p = 0.036) and OS (HR = 0.58; 95% CI = 0.36–0.95; p = 0.029). ACh showed consistent benefit in DFS and OS for patients with albumin >3.5 g/dL, lymphovascular and perineural invasion, pT4, pN2–3, pathologic stage (PS) IIIA and IIIB and lymph node ratio (LNR) > 13.1.ConclusionThese data suggest that adjuvant capecitabine and oxaliplatin reduce the recurrence and mortality in patients with stage II–III gastric cancer who underwent D2 gastrectomy. PS IIIA and IIIB and LNR > 13.1 benefited more from receiving adjuvant chemotherapy and poorly cohesive gastric carcinoma did not significantly reduce the rates of survival.

105: SURGICAL DISSECTION DOES NOT INCREASE FREE CANCER CELLS (FCC) IN PERITONEAL LAVAGE OF PATIENTS FOLLOWING D2 GASTRECTOMY

Abstract Background and aim Peritoneal free cancer cells (FCC) in patients with gastric cancer (GC) is poor prognostic factor. D2 gastrectomy dissection may induce exfoliated FCC spread from primary tumour or involved lymph nodes (LN). Conventional cytology for FCC detection has several limitations, and prophylactic use of extensive intraoperative peritoneal lavage (IPL) does not improve survival. A prospective single-arm observational study was conducted to verify whether D2 gastrectomy causes an increase of FCC in peritoneal lavage as in patients with GC following D2 gastrectomy. Methods Thirty GC patients underwent D2 gastrectomy, followed by objective quantitative measurements of CK19 mRNA level reflecting FCC with One-Step Nucleic Acid Amplification (OSNA) assay. The IPL with 3000 cc of saline was performed twice after: (1) gastrectomy with D2 lymphadenectomy; and (2) alimentary tract reconstruction. The IPL samples were analysed by initial cytology and four (1–4) consecutive OSNA assays (Figure 1). Three patients were excluded due to positive cytology in samples obtained after laparotomy. Results Initial OSNA measurement (1) revealed positive results (≥24.6 cCP/μl) in 7 (29.6%) patients. Subsequent OSNA measurements revealed a significant decrease in the FCC level after removal of the primary tumour with regional LNs (D2 gastrectomy) (1 vs 2; medians [95%CI]: 4.6 [1.1–18.5] vs. 0.00004 [0–0.2] cCP/μl; P = 0.0012). The first IPL induced non-significant increase in the FCCs (2 vs 3, medians [95%CI]: 0.00004 [0–0.2] vs 0 [0–0.5] cCP/μl; P = 0.3300), but the second IPL reversed it to normal levels (3 vs 4, medians [95%CI]: 0 [0–0.5] vs 0 [0–0] cCP/μl; P = 0.0.0574). At this point of operation, additional finding was a trend toward temporal increase of FCC in patients with LN involvement (pN1–3)(2 vs 3; medians [95%CI]: 0 [0–0.2] vs 0 [0–42.8] cCP/μl; P = 0.0674). One patient was still positive (FCC) at the end of operation as measured by OSNA (4). Conclusion D2 Gastrectomy does not induce increase in the peritoneal FCCs. Temporal intraoperative increase in peritoneal FCC after the IPL may be observed, especially in tumours with LN metastases. At least two consecutive IPLs (with min. 3000 mL of saline) are necessary to reverse temporal increase of peritoneal FCC.

Early experience with total robotic D2 gastrectomy in a low incidence region: surgical perspectives

BackgroundFew European centers have reported on robotic gastrectomy for malignancy. We report our early experience with curative-intent total robotic gastrectomy.Materials and methodsThe Intuitive Surgery Da Vinci Surgical System Xi 4 armed robot was used. Routine D2 lymphadenectomy was applied.ResultsSome 27 patients with adenocarcinoma (n = 18), hereditary cancer susceptibility (n = 8) and premalignancy (n = 1) were allocated to robotic gastrectomy, three were excluded due to inoperability during surgery. Median (range) age was 66 (18–87) years, 14 (58.3%) were females and body mass index was 25.5 (22.1–33.5) kg/m2. Total gastrectomy was performed in 19 (79.2%) and subtotal in five (20.8%) patients. One (4.2%) procedure was converted to laparotomy. Procedural time was 273 (195–427) minutes. Three (12.5%) patients were reoperated within 30 days, one (4.2%) died. Serious complications (Clavien Dindo IIIb or more) occurred in three (12.5%) patients. Postoperative hospital stay was 10 (6–43) days. Fourteen of 16 (87.5%) patients with adenocarcinoma/premalignancy received radical resections. The median number of harvested lymph nodes was 20 (11–34). Eleven (73.3%) patients with adenocarcinoma had T3/T4 tumors and 6 (40%) had TNM stage III or more.ConclusionTotal robotic D2 gastrectomy appears feasible and safe during early introduction in a low incidence region.

Health-Related Quality of Life in Patients With Locally Advanced Gastric Cancer Undergoing Perioperative or Postoperative Adjuvant S-1 Plus Oxaliplatin With D2 Gastrectomy: A Propensity Score-Matched Cohort Study.

BackgroundSome high-quality clinical trials have proven the efficacy and safety of perioperative and postoperative S-1 with oxaliplatin (peri-SOX and post-SOX) for patients with locally advanced gastric cancer (LAGC) undergoing D2 gastrectomy. However, little is known about how health-related quality of life (HRQOL) changes over time in patients receiving peri-SOX or post-SOX chemotherapy.MethodsA prospective observational cohort (NCT04408859) identified 151 eligible patients with LAGC who underwent D2 gastrectomy with at least six cycles of peri-SOX or post-SOX chemotherapy from 2018 to 2020. HRQOL was assessed using the EROTC QLQ-C30 and its gastric module, QLQ-STO22, at indicated measurements, including the baseline, 1st, 3rd, 6th and 12th month after initiation of therapy. Baseline characteristics, therapeutic effects, and longitudinal HRQOL were compared between the peri-SOX and post-SOX groups after propensity score matching. HRQOL changes over time and the risk factors for scales with severe deterioration were further analyzed.ResultsNo statistically significant differences in longitudinal HRQOL were observed between patients in the peri-SOX and post-SOX groups, with comparable surgical outcomes and adverse chemotherapy events. Scales of social functioning, abnormal taste, and anxiety improved earlier in the peri-SOX group than in the post-SOX group. Score changes in both groups indicated that general deterioration and slower recovery usually occurred in the scales of physical, social, and role functioning, as well as symptoms of fatigue, reflux, diarrhea, and anxiety.ConclusionPeri-SOX showed a longitudinal HRQOL comparable to post-SOX in patients with LAGC who underwent D2 gastrectomy. The peri-SOX group had better performance in social functioning, abnormal taste, and anxiety at some measurements.

Preoperative Low Prealbumin Is Associated With Recurrence in Patients With Stage II/III Gastric Cancer After Laparoscopic D2 Gastrectomy.

BackgroundPostoperative recurrence is associated with poor prognosis in patients with gastric cancer. This study aimed to explore predictive factors contributing to recurrence in patients with stage II/III gastric cancer after laparoscopic D2 gastrectomy.MethodsThis retrospective study was conducted at a single tertiary referral hospital. Patients diagnosed with gastric cancer who met the inclusion criteria were included in the study. The clinicopathological characteristics of the patients were collected. The patients were divided into recurrence and non-recurrence groups. The predictive factors were investigated using univariate and multivariate analyses.ResultsIn total, 462 patients were included. The incidence of recurrence was 26.4% (122/462) in all patients. The most common recurrence pattern was haematogenous recurrence. In the multivariate analysis, the independent predictive factors for recurrence were serum prealbumin level (p < 0.001), prognostic nutritional index (p = 0.001), carbohydrate antigen 19-9 (CA19-9) (p < 0.001), number of lymph node metastases (p < 0.001), signet-ring cell carcinoma (p = 0.001), tumor deposit (p = 0.001), and no/incomplete adjuvant chemotherapy (p < 0.001).ConclusionsOur findings revealed that nutritional status was an independent predictive factor for recurrence in patients with gastric cancer after D2 gastrectomy. We suggest that patients with risk factors for recurrence receive both nutritional support and intense surveillance.

Laparoscopic versus open subtotal gastrectomy for locally advanced gastric cancer: A retrospective analysis from a single institution

/Objective: Laparoscopic distal gastrectomy for early gastric cancer is described as a treatment option in general practice. However, the oncological efficacy and technical safety of laparoscopic gastrectomy with D2 lymphadenectomy in locally advanced gastric cancer are controversial, and clinical trials are ongoing. This study aimed to evaluate the short-term and surgical outcomes between laparoscopic and open gastrectomy procedures in locally advanced gastric cancer. We retrospectively analyzed data from 134 patients who underwent subtotal D2 gastrectomy for locally advanced gastric cancer in our hospital between January 2011 and December 2018. Clinicopathological characteristics, surgical outcome, postoperative recovery, disease-free survival, and overall survival were compared between those who underwent laparoscopic and open gastrectomies. Baseline characteristics were similar between patients who underwent open and laparoscopic surgeries. Less surgical time (250.8 vs. 347.6min in laparoscopic vs. open surgery, respectively; P<0.05) and lower blood loss (83.7 vs. 333mL in laparoscopic vs. open surgery, respectively; P<0.05) were noted in patients who underwent laparoscopic surgery than in those who underwent open gastrectomy. The time of starting oral intake was earlier and the length of postoperative hospital stay was shorter in the laparoscopic group than in the open group. Surgical morbidity and mortality rates, as well as disease-free survival and overall survival rates, did not differ between the two groups. Laparoscopic gastrectomy is feasible and safe for locally advanced gastric cancer. Based on the perioperative results and short-term outcomes, laparoscopic gastrectomy is non-inferior to open gastrectomy.

D2 lymphadenectomy with complete mesogastrium excision vs. conventional D2 gastrectomy for advanced gastric cancer.

Background:The complete mesogastrium excision (CME) based on D2 radical gastrectomy is believed to significantly reduce the local-regional recurrence compared with D2 radical gastrectomy in advanced gastric cancer, and it is widely used in China. This study aimed to explore whether D2 + CME is superior to D2 on surgical outcomes during gastrectomy from Chinese data.Methods:Feasible studies comparing the D2 + CME (D2 + CME group) and D2 (D2 group) published up to March 2020 are searched from electronic databases. The data showing surgical and complication outcomes are extracted to be pooled and analyzed.Results:Fourteen records including 1352 patients were included. The D2 + CME group had a shorter mean operative time (weighted mean difference [WMD] = —16.72 min, 95% confidence interval [CI]: −26.56 to −6.87 min, P < 0.001), lower mean blood loss (WMD = −39.08 mL, 95% CI: −49.94 to −28.21 mL, P < 0.001), higher mean number of retrieved lymph nodes (WMD = 2.13, 95% CI: 0.58–3.67, P = 0.007), shorter time to first flatus (WMD = −0.31 d, 95% CI: −0.53 to − 0.10 d, P = 0.005), and postoperative hospital days (WMD = −1.09, 95% CI: −1.92 to −0.25, P = 0.010) than the D2 group. Subgroup analysis suggested that the advantages from the D2 + CME group were obvious in traditional open radical gastrectomy, proximal gastrectomy, and distal gastrectomy compared with D2 group. The evaluations of post-operative complications showed that the patients who underwent D2 + CME had a lower incidence of post-operative complications than the patients who underwent D2 surgery alone (relative risk [RR] = 0.65, 95% CI: 0.45–0.87, P = 0.003). The D2 radical gastrectomy plus CME improved 3-year overall survival (OS) (RR = 1.16, 95% CI: 1.02–1.32, P = 0.020) and lowered the local recurrence rate (RR = 0.51, 95% CI: 0.28–0.94, P = 0.030). The patients undergoing laparoscopic surgery or total gastrectomy had more significant advantages compared between D2 + CME and D2 groups in 3-year OS.Conclusion:The data from China show that D2 radical gastrectomy plus CME are reliable procedures and safety compared to D2 radical gastrectomy with faster recovery, lower risk, and better prognosis.

Comparison of D2 versus D1 gastrectomy in Kashmiri patients in a tertiary care cancer centre

Background: The aim of this study was to compare the clinical outcomes, survival, morbidity and mortality of D1 and D2 gastrectomy in Kashmiri population in a high-volume tertiary care centre.Methods: Data were collected retrospectively from the prospective database maintained by Department of Surgical Gastroenterology at SKIMS, Kashmir India. We did direct comparison of D1 and D2 gastrectomy in gastric cancer patients who underwent surgery between January 2016 to December 2021 and fulfilled the eligibility criteria. A total of 98 patients were included in the study of which 46 underwent a D1 gastrectomy and 52 underwent a D2 gastrectomy.Results: Male-female ratio was 3:1 in both groups with a mean age of 61 years. There was no significant difference in terms of age or gender between D1 and D2 groups (p&gt;0.05). The mean number of harvested lymph nodes (LN) was (7±1.9) in the D1 group compared to (27.6±10.1) the D2 group (p=0.001). Average hospital stay was comparable in both groups. The median survival was 26 months for the D2 and 19 months for the D1 group (p≤0.01). The survival in the D2 group was significantly higher than in the D1 group. There was no difference in postoperative complications between two groups in our study.Conclusions: our study indicates that D2 gastrectomy should be the standard of treatment for advanced stage II /III disease as it improves the survival outcome in these patients without affecting overall hospital stay, morbidity and mortality.

Comparison of the Efficacy of D2 Gastrectomy Plus Liver Radiofrequency Combined With Chemotherapy Versus Chemotherapy Alone in the Treatment of Advanced Gastric Cancer With Unresectable Synchronous Liver Metastases: A Multicenter Randomized Controlled Trial Protocol.

BackgroundWhether patients with advanced gastric cancer with unresectable synchronous liver metastases require surgical treatment remains a controversial topic among surgeons. Recently, an open-label multicenter, international RCT study show that compared with chemotherapy alone, gastric resection combined with chemotherapy had no survival advantage for advanced gastric cancer with unresectable synchronous liver metastases. A limitation of this study was that gastrectomy for gastric cancers was restricted to D1 lymphadenectomy and no metastatic lesions were removed. Whether D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy could provide benefits to these patients is worthy of further confirmation by high-level evidence-based medicine.Methods/DesignThis study will investigate the efficacy of D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy compared to chemotherapy alone in a prospective, multicenter, randomized controlled trial that will enroll 200 patients who have advanced gastric cancer with unresectable synchronous liver metastases. The patients will be randomly divided into two groups: the test group (D2 gastrectomy plus liver radiofrequency plus postoperative chemotherapy, n=100) and the control group (chemotherapy alone, n=100). The patients’ general information, past medical history, laboratory tests, imaging results, surgery details, and chemotherapy details will be recorded and analysed. The overall survival (OS) will be recorded as primary endpoints. Progression-free survival (PFS) and the total incidence of complications will be recorded as secondary endpoints.DiscussionThis study is to establish a multicentre randomized controlled trial to compare the efficacy of D2 gastrectomy plus liver radiofrequency combined with postoperative chemotherapy versus chemotherapy alone.Trial RegistrationChinese Clinical Trial Registry, Approved No. of ethics committee:ChiECRCT20200331. Registered on 15 November 2020. Registration number:ChiCTR2000039964. The study has received full ethical and institutional approval.Advantages and Limitations of this StudyThis is the first clinical trial that will provide evidence on the efficacy of D2 gastrectomy plus liver radiofrequency combined with chemotherapy versus chemotherapy alone for the treatment of advanced gastric cancer with unresectable synchronous liver metastases. A prospective RCT with 200 patients who have advanced gastric cancer with unresectable synchronous liver metastases.Clinical Trial Registration[https://www.chictr.org.cn/], identifier ChiCTR2000039964.

Preclinical evaluation of a dual magnetic and fluorescence-guided approach for sentinel lymph node biopsy in the stomach.

337 Background: Gastrectomy with extended (D2) lymphadenectomy is considered as a standard of care for gastric cancer to provide best possible outcomes and pathologic staging. However, D2 gastrectomy is technically demanding operation and reported to be associated with increased complications, including bleeding, pancreatitis, abscess, chylous ascites, and mortality. Application of sentinel lymph node mapping in gastric cancer has the potential to reduce patient morbidity, while facilitating detailed pathology processing required to accurately identify nodal metastases. However, sentinel lymph node biopsy techniques are not established for gastrectomy because of a lack of practical tracers; an effective and convenient tracer that exclusively accumulates in sentinel lymph nodes is critically needed. Methods: A lymphotropic tracer solution consisting of mannose-labelled magnetic nanoparticles (SPIONs) and a fluorescent dye (indocyanine green, ICG) was injected laparoscopically into the stomach submucosa of 6 healthy female domesticated pigs while under general anaesthesia. Intraoperative laparoscopic fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while a combination of T2-weighted MRI and magnetometer probe detection were used to identify nodes containing SPIONs. Results: Mixing the ICG dye and SPIONs ensured concurrence of fluorescent and magnetic signals in the sentinel nodes. Average tracer accumulation time before dissection was 5 hours. On average 4.5 fluorescent nodes (range 2–7) were removed, of which 2 (average) were also magnetic (range 1–4). Magnetic nodes could be identified using both preoperative MRI and intraoperative magnetometer probe. The mannose label of the SPIONs produced a strong binding affinity to macrophages, and in combination with particle size (80 nm) results in enhanced retention in the sentinel nodes. On average, after 5 hours accumulation time, the sentinel nodes contained 4.1% of the SPION injected dose and 88% of the magnetometer counts. Conclusions: Through the co-injection of fluorescent and mannose-labelled magnetic tracers, lymphatic drainage pathways can be determined preoperatively with MRI, visualised with intraoperative fluorescence cameras, and SLNs confirmed with magnetometer. Although ICG flows through multiple echelons, in doing so it creates a lymphatic roadmap to guide surgeons. The addition of magnetic particles provides sentinel node discrimination, so in combination, these two tracers could greatly enhance the capability to detect SLNs in gastric cancer.

Perioperative sintilimab combination with SOX for resectable locally advanced gastric/gastroesophageal junction cancer(GC/GEJC): Initial findings of a single-arm phase II trial.

294 Background: Perioperative treatment is very important to improve long-term survival for gastric/gastroesophageal junction cancer(GC/GEJC), The RESOLVE study showed that perioperative-SOX have a clinically meaningful improvement in patients with locally advanced GC/GEJC who had D2 gastrectomy. Adding PD-1 inhibitor to the chemotherapy have shown significant clinical benefits in first-line treatment of GC/GEJC. This trial was designed to assess the feasibility and efficacy of this combination in perioperative treatment of resectable locally advanced GC/GEJC. Methods: This is a prospective, single-arm, single-center phase II study. Patients of histopathology confirmed locally advanced GC/GEJC, with clinical stage II-IV A per AJCC8th, ECOG PS 0-1, were enrolled and treated with 3 cycles of preoperative sintilimab (200mg, iv, d1) and SOX (oxaliplatin 130mg/m2, iv, d1 and S-1 40-60mg, po, bid, d1-14) every 3 weeks, and 12 months of postoperative sintilimab (200mg, iv, d1) and S-1 (40-60mg, po, bid, d1-14) every 3 weeks. The primary endpoint was 2-year DFS rate. The second endpoints were pCR, MPR, R0 resection rate, safety and 3-year OS. Results: As of June 2021, 21 patients were enrolled, with median age 56 years (range 31-72 years), males 10 (47.6%), cT2/3/4a/4b 2(9.5%)/0/16(76.2%)/3(14.3%), cN1/N2 7(33.3%)/14(66.7%) and GC/GEJC 14(66.7%)/7(33.3%). All 21 patients had completed gastrectomy. 7 patients (33.3%) achieved pathological complete response (pCR), 8 patients (38.1%) had major response (TRG 0-1) and 21 patients (100%) achieved R0 resection. Common TRAEs were anemia (38.1%), lymphopenia (28.6%), neutropenia (19.0%), leukopenia (14.3%), ALT increase (9.5%), AST increase (4.8%), thrombocytopenia (4.8%). Grade 3 or more TRAEs included anemia (9.5%). There were no severe complications and death related to the operation. The median postoperative hospital stay was 10 days (range 7-41 days). Conclusions: Adding sintilimab to the chemotherapy resulted in an encouraging pCR and MPR as perioperative treatment for resectable locally advanced GC/GEJC, and safety was manageable. A Phase II randomized study is ongoing. Clinical trial information: ChiCTR2100043572.

Is D2 laparoscopic gastrectomy essential for elderly patients with advanced gastric cancer? A propensity score matched analysis

The necessity of the standard D2 gastrectomy for elderly patients with advanced gastric cancer (GC) is controversial because only limited data are available to demonstrate its oncological benefit for them. Our aim was to compare the outcomes of D2 and Non-D2 and to evaluate the survival benefit of D2 laparoscopic gastrectomy (LG) in elderly patients. We retrospectively identified 865 patients with GC who underwent radical LG at our hospital between 2011 and 2017. Patients aged ≥75 years who were diagnosed with clinical T1N+ or clinical T2-4 were eligible. The primary outcome was the 3-year overall survival (OS) rate. The confounding factors were minimized using propensity score matching. This study included 119 patients (63 D2 LG and 56 Non-D2 LG), and 52 patients (26 each for D2 LG and Non-D2 LG) were analyzed after matching. Although no significant difference was found in overall major complications (P=1.00), complications tended to occur in the D2 group (D2 vs. Non-D2 =3.9% vs. 0%). No differences in the 3-year OS were noted between the two groups (68.8% vs. 68.8%; HR 1.53, 95% CI: 0.56-3.19). This study demonstrated the possible association between D2 LG and increased complication rate and no survival benefit of D2 LG in elderly patients.

Benefit for single-agent adjuvant chemotherapy in elderly patients with locally advanced gastric adenocarcinoma

Current NCCN guidelines exclude the possibility of using single-agent adjuvant chemotherapy in locally advanced gastric adenocarcinoma, while allowing doublet chemotherapy. However, single-agent adjuvant chemotherapy is a valid treatment option in other gastrointestinal malignancies, preferred for elderly and/or frail patients. The current study used a nationwide oncology database to assess the benefit of single-agent adjuvant chemotherapy, specifically in the elderly population. Using the National Cancer Database (2004-2016) we identified 1953 individuals with non-metastatic gastric adenocarcinoma who underwent upfront D2 gastrectomy with pathologic stage ≥ T3 or Npos and free surgical margins, and had not received either preoperative chemotherapy or pre-/postoperative radiotherapy. We used IPTW analysis to compare overall survival between individuals receiving either single- or multi-agent adjuvant chemotherapy, or referred to observation alone. Individuals receiving single-agent chemotherapy had an overall survival benefit compared with observation alone, with an HR of 0.70 (95% CI 0.55-0.88, p < 0.001). Individuals over the age of 65 had an OS benefit with an HR of 0.61 (95% CI 0.46-0.82, p < 0.001). Comparing individuals over the age of 65 receiving single- vs. multi-agent chemotherapy, there was no overall survival difference with an HR of 0.87 (95% CI 0.64-1.18, p = 0.38). Single-agent adjuvant chemotherapy with a fluoropyrimidine in locally advanced gastric adenocarcinoma following D2 gastrectomy can improve overall survival in elderly patients. Clinicians may consider using either capecitabine or 5-FU as a treatment option in the adjuvant setting for this age group.

Ex Situ In Vivo Technique of Spleen-Preserving Splenic Hilar Lymph Node Dissection in Operable Proximal Gastric Adenocarcinoma.

D2 gastrectomy is the globally accepted standard surgical procedure for operable gastric cancer, and lymph node (LN) dissection is considered as the critical part of radical surgery and closely related to the prognosis. The splenic hilar LN (SHLN) or level 10 are to be removed during standard D2 total gastrectomy. In situ and ex situ spleen-preserving lymphadenectomies have been the most common dissection approaches for SHLNs. No study exists which compares the outcomes of these techniques in Indian population. This study is aimed to analyse the operative outcomes of ex situ in vivo technique of spleen-preserving splenic hilar lymph node dissection in patients who underwent D2 total gastrectomy for operable proximal gastric cancer in comparison with in situ in vivo technique of splenic hilar lymph node dissection. We reviewed prospectively collected data from 17 patients with operable proximal gastric cancer between September 2016 and April 2019 who underwent D2 total gastrectomy with splenic hilar lymph node dissection and studied the preoperative demographic factors, operative and postoperative outcomes comparing the different operative techniques. Patients with oesophago-gastric junction involvement, direct splenic or other adjacent organ invasion requiring multivisceral resection and gastric stump carcinoma were excluded. Overall, 17 patients underwent D2 total gastrectomy for operable gastric cancer. Mean age of presentation was 54.7 years including 13 males and 4 females. Five patients had middle third and 12 patients had upper third cancer. All patients had splenic hilar nodal clearance as follows: in situ - 14 and ex situ - 3 patients. R0 resection was achieved in all patients. Lymph node harvest tends to be higher with lower operative time and blood loss in patients with ex situ technique compared to in situ technique with similar morbidity. Ex situ in vivo technique of spleen-preserving splenic hilar lymph node dissection can be considered as both safe and feasible procedure for operable proximal gastric cancer patients in experienced centres to achieve better lymph node yield with no significant increase in morbidity.

Endoscopic ultrasonography-guided antegrade stenting in surgically altered anatomy: Case report and review of literature

Endoscopic ultrasonography-guided biliary drainage (EUS-BD) remains an alternative to Endoscopic retrograde cholangiopancreatography (ERCP) for malignant extrahepatic biliary obstruction. Biliary drainage in altered surgical anatomy remains a challenge to endoscopists. Enteroscopy-assisted ERCP (eERCP) has been utilised for biliary access in patients with altered surgical anatomy, but with suboptimal results. We report a case of 51-year-old male, a case of carcinoma stomach undergone distal D2 gastrectomy with gastrojejunostomy with distal biliary obstruction, who underwent EUS-BD antegrade approach with technical and clinical success, with a review of literature of EUS BD in altered surgical anatomy.

Application of collagen matrix in the prevention of anastomotic leaks following D2 gastrectomy with Roux-en-Y anastomosis.

Esophagoenteral anastomotic leaks are one of the most serious complications of gastric cancer surgeries. Leaking anastomosis has a negative impact on patient&apos;s prognosis as it translates into increased reoperation rates, direct and indirect mortality, as well as increased risk of cancer recurrence. Literature contains reports on the use of additional measures aimed at preventing anastomotic leaks. Collagen matrices with tissue adhesives used to prevent anastomotic leaks following D2 gastrectomy with Roux-en-Y anastomosis have not been described well in Polish literature. However, international reports on such use of these materials are available. Collagen matrices have been successfully applied in selected patients undergoing total or subtotal gastrectomy at the Department of General, Minimally Invasive, and Gastroenterological Surgery. We hereby present our experience in a group of 6 patients presenting with anastomotic leak risk factors.