The efficacy of simple oral nutritional supplements versus usual care in postoperative patients with gastric cancer: study protocol for a multicenter, open-label, parallel, randomized controlled trial.

BACKGROUND: Body weight loss (BWL) after gastrectomy impact on the short- and long-term outcomes. Oral nutritional supplement (ONS) has potential to prevent BWL in patients after gastrectomy. However, there is no consistent evidence supporting the beneficial effects of ONS on BWL, muscle strength and health-related quality of life (HRQoL). This study aimed to evaluate the effects of ONS formulated primarily with carbohydrate and protein on BWL, muscle strength, and HRQoL. METHODS: This will be a multicenter, open-label, parallel, randomized controlled trial in patients with gastric cancer who will undergo gastrectomy. A total of 120 patients who will undergo gastrectomy will be randomly assigned to the ONS group or usual care (control) group in a 1:1 ratio. The stratification factors will be the clinical stage (I or ≥ II) and surgical procedures (total gastrectomy or other procedure). In the ONS group, the patients will receive 400 kcal (400 ml)/day of ONS from postoperative day 5 to 7, and the intervention will continue postoperatively for 8 weeks. The control group patients will be given a regular diet. The primary outcome will be the percentage of BWL (%BWL) from baseline to 8 weeks postoperatively. The secondary outcomes will be muscle strength (handgrip strength), HRQoL (EORTC QLQ-C30, QLQ-OG25, EQ-5D-5L), nutritional status (hemoglobin, lymphocyte count, albumin), and dietary intake. All analyses will be performed on an intention-to-treat basis. DISCUSSION: This study will provide evidence showing whether or not ONS with simple nutritional ingredients can improve patient adherence and HRQoL by reducing BWL after gastrectomy. If supported by the study results, nutritional support with simple nutrients will be recommended to patients after gastrectomy for gastric cancer. TRIAL REGISTRATION: jRCTs051230012; Japan Registry of Clinical Trails. Registered on Apr. 13, 2023.

Comparison of Minimally Invasive Surgery with Open Surgery for Remnant Gastric Cancer: A Multi-institutional Cohort Study.

BACKGROUND: Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for remnant gastric cancer (RGC) remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. PATIENTS AND METHODS: Patients with RGC who underwent surgery between 2005 and 2020 at 17 institutions were included, and a propensity score matching analysis was performed to compare the short- and long-term outcomes of MIS with open surgery. RESULTS: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 [95% confidence interval (CI): 0.45, 1.27] and 0.65 (95% CI: 0.32, 1.29), respectively. The MIS group had significantly less blood loss [mean difference (MD), -409 mL; 95% CI: -538, -281] and a shorter hospital stay (MD, -6.5 days; 95% CI: -13.1, 0.1) than the open surgery group. The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival were 77.9% and 76.2% in the MIS and open surgery groups, respectively [hazard ratio (HR), 0.78; 95% CI: 0.45, 1.36]. The 3-year relapse-free survival were 71.9% and 62.2% in the MIS and open surgery groups, respectively (HR, 0.71; 95% CI: 0.44, 1.16). CONCLUSIONS: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC.

Limited Oncological Benefits of Laparoscopic Total Gastrectomy With Splenectomy for Patients With Type 4 or Large Type 3 Gastric Cancer.

BACKGROUND/AIM: Total gastrectomy with splenectomy (TGS) is routinely performed in patients with type 4 or large type 3 gastric cancer (GC), which sometimes metastasize to splenic hilar lymph nodes (LNs). However, the indication for and significance of TGS remain controversial. This multicenter retrospective study aimed to evaluate the oncological feasibility of laparoscopic TGS (LTGS) in patients with advanced proximal GC. PATIENTS AND METHODS: We retrospectively studied patients with type 4 or large type 3 GC who underwent LTGS at three Institutes between January 2010 and December 2018. RESULTS: We identified 26 consecutive eligible patients for analysis. Large type 3/type 4 were observed in 10 (38.5%)/16 (61.5%) cases. Involvement of the greater curvature was observed in 19 cases (73.1%), and GC spread to the whole stomach was observed in 12 cases (46.2%). R0 resection was achieved in 23 cases (88.5%). The median number of retrieved splenic hilar LNs was 4.0 (1-15), and the number of cases with splenic hilar LN metastasis was 3 (11.5%). Postoperative grade II intra-abdominal abscess was observed in 1 case (3.8%), and pancreatic fistula was not observed in any patient. Recurrence was observed in 18 cases (69.2%), of which 16 (88.9%) presented peritoneal recurrence. The median overall survival (OS) was 40.6 months, and the 5-year OS rate was 30.3%. The 5-year survival rate of patients with splenic hilar LN metastasis was 33.3% and the therapeutic value of splenectomy was 3.83. CONCLUSION: LTGS was performed safely, but the oncological benefit of the procedure for type 4 or large type 3 GC was very limited.

Safety assessment of robotic gastrectomy and analysis of surgical learning process: a multicenter cohort study.

BACKGROUND: The safety of robotic gastrectomy (RG) for gastric cancer in daily clinical settings and the process by which surgeons are introduced and taught RG remain unclear. This study aimed to evaluate the safety of RG in daily clinical practice and assess the learning process in surgeons introduced to RG. METHODS: Patients who underwent RG for gastric cancer at Kyoto University and 12 affiliated hospitals across Japan from January 2017 to October 2019 were included. Any morbidity with a Clavien-Dindo classification grade of II or higher was evaluated. Moreover, the influence of the surgeon's accumulated RG experience on surgical outcomes and surgeon-reported postoperative fatigue were assessed. RESULTS: A total of 336 patients were included in this study. No conversion to open or laparoscopic surgery and no in-hospital mortality were observed. Overall, 50 (14.9%) patients developed morbidity. During the study period, 14 surgeons were introduced to robotic procedures. The initial five cases had surprisingly lower incidence of morbidity compared to the following cases (odds ratio 0.29), although their operative time was longer (+ 74.2 min) and surgeon's fatigue scores were higher (+ 18.4 out of 100 in visual analog scale). CONCLUSIONS: RG was safely performed in actual clinical settings. Although the initial case series had longer operative time and promoted greater levels of surgeon fatigue compared to subsequent cases, our results suggested that RG had been introduced safely.

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

Background: 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. Methods: 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. Results: 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). Conclusions: This study demonstrated the possible association between D2 LG and increased complication rate and no survival benefit of D2 LG in elderly patients.

Mesenteric closure after laparoscopic total gastrectomy with Roux-en-Y reconstruction is effective for prevention of internal hernia: a multicenter retrospective study.

BACKGROUND: Internal hernia (IH) is one of the critical complications after gastrectomy with Roux-en-Y reconstruction, which can be prevented by closing mesenteric defects. However, only few studies have investigated the incidence of IH after laparoscopic total gastrectomy (LTG) with Roux-en-Y reconstruction for gastric cancer till date. This study aimed to assess the efficacy of defect closure for the prevention of IH after LTG. METHODS: This multicenter, retrospective cohort study collected data from 714 gastric cancer patients who underwent LTG with Rou-en-Y reconstruction between 2010 and 2016 in 13 hospitals. We evaluated the incidence of postoperative IH by comparing closure and non-closure groups of Petersen's defect, jejunojejunostomy mesenteric defect, and transverse mesenteric defect. RESULTS: The closure group for Petersen's defect included 609 cases, while the non-closure group included 105 cases. The incidence of postoperative IH in the closure group for Petersen's defect was significantly lower than it was in the non-closure group (0.5% vs. 4.8%, p < 0.001). The closure group for jejunojejunostomy mesenteric defect included 641 cases, while the non-closure group included 73 cases. The incidence of postoperative IH in the closure group of jejunojejunostomy mesenteric defect was significantly lower than that in the non-closure group (0.8% vs. 4.1%, p = 0.004). Out of 714 patients, 41 underwent retro-colic reconstruction. No patients in the transverse mesenteric defect group developed IH. CONCLUSION: Mesenteric defect closure after LTG with Roux-en-Y reconstruction may reduce postoperative IH incidence. Endoscopic surgeons should take great care to prevent IH by closing mesenteric defects.

Side-overlap esophagogastric tube (SO-EG) reconstruction after minimally invasive Ivor Lewis esophagectomy or laparoscopic proximal gastrectomy for cancer of the esophagogastric junction.

PURPOSE: Both laparoscopic proximal gastrectomy with lower esophagectomy (extended LPG) and minimally invasive Ivor Lewis esophagectomy (MIILE) are acceptable treatments for adenocarcinoma of the esophagogastric junction (AEG), but the optimal reconstruction technique for mediastinal esophagogastrostomy (one that provides adequate reflux prevention) has not been established. We devised a novel side-overlap esophagogastric-tube (SO-EG) reconstruction. METHODS: We performed a retrospective review of patient records after LPG or MIILE. In each patient, we created a 3-cm wide gastric tube, overlapping the esophagus by 5 cm. A linear stapler was inserted into the left side of the esophageal stump and the anterior gastric wall along the greater curvature. The entry hole was closed to make a slit-like anastomosis, and the right side of the esophageal wall was fixed to the anterior gastric wall. RESULTS: Ten consecutive patients underwent this procedure between June 2020 and July 2021. Five patients had Siewert type II AEG: 4 with lower thoracic esophageal cancer and 1 with benign lower esophageal stenosis. A total of 3 patients underwent extended LPG, and 7 underwent MIILE. The median operative time was 352 min (range, 221-556 min). The postoperative course was uneventful in 9 patients; a single patient developed pneumonia. Seven patients underwent follow-up endoscopy at 6 months. One patient with anastomotic stenosis and 2 with mild reflux esophagitis were treated conservatively. CONCLUSION: Our novel SO-EG reconstruction is simple and feasible, with acceptable results for preventing reflux esophagitis. This technique can be performed with either extended LPG or MIILE.

PTEN is a predictive biomarker of trastuzumab resistance and prognostic factor in HER2-overexpressing gastroesophageal adenocarcinoma.

Poor trastuzumab (Tmab) response of patients with human epidermal growth factor receptor 2-overexpressing gastric or gastroesophageal junction adenocarcinoma (HER2-GEA) is associated with the inhibition of phosphatase and tensin homolog (PTEN) expression. In this multicenter, retrospective observational study, pathological samples of patients with HER2-GEA receiving Tmab-combined chemotherapy were immunohistochemically analyzed for PTEN expression. The primary endpoints were disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). We assessed the effect of conventional chemotherapy and Tmab alone or combined with PI3K pathway inhibitors in vitro in HER2-GEA cells with or without PTEN expression. Twenty-nine and 116 patients were in the PTEN-loss and PTEN-positive groups, respectively. In patients with the target region, DCR was significantly lower in PTEN-loss patients than in PTEN-positive patients (67% and 87%, respectively, p = 0.049). The multivariate analysis demonstrated that PTEN loss was significantly associated with shorter PFS (HR = 1.63, p = 0.035) and OS (HR = 1.83, p = 0.022). PTEN knockdown did not affect the cytostatic effect of 5-FU and cisplatin, whereas Tmab combined with the PI3K/mTOR inhibitor NPV-BEZ235 suppressed PTEN-knockdown cell proliferation. In patients with HER2-GEA, PTEN loss is a predictive biomarker of Tmab resistance and prognostic factor. Molecular-targeted therapy with a PI3K/mTOR inhibitor would be effective for HER2-GEA with PTEN loss.

Functional Outcomes of Delta-Shaped Anastomosis After Laparoscopic Distal Gastrectomy.

BACKGROUND: We invented a simple and secure method of intracorporeal gastroduodenostomy, the delta-shaped anastomosis (DA), using endoscopic linear stapler only and standardized the DA procedure by resecting two-thirds of the stomach based on the anatomical landmarks. This study aimed to evaluate the feasibility of the standardized DA as the standard reconstruction procedure after a laparoscopic distal gastrectomy assessing functional outcomes including postoperative complications, body weight loss, nutritional status, and endoscopic findings. METHODS: The medical records of 349 patients with gastric cancer who underwent laparoscopic distal gastrectomy from April 2011 to December 2017 at our hospital were retrospectively reviewed. Functional outcomes were assessed according to nutritional status and endoscopic findings. RESULTS: The operation time was shorter and complication rate was lower in the standardized DA than those in Billroth-II (BII) and Roux-en-Y (RY). The body weight loss in DA was 10% 1 year postoperatively and remained stable during the follow-up period, which showed no significant difference. The endoscopic findings showed the ratio of residual food in DA was lower than that in RY (DA:RY = 13.3%:13.6% and 8.4%:33.3% at 1 and 3 years postoperatively, respectively). Severe gastritis was extremely rare in DA (6.7% at 1 year and 15.6% at 3 years postoperatively). Bile reflux was more often found in DA than RY (DA:RY = 19.9%:4.8% and 26.6%:0% at 1 and 3 years postoperatively, respectively). Reflux esophagitis was found 10% of DA only. CONCLUSIONS: Functional outcomes of the standardized DA were satisfactory and feasible. Our intracorporeal Billroth-I reconstruction, by resecting two-thirds of the stomach, can be one of the standard reconstruction methods after a laparoscopic distal gastrectomy.

Comparative Outcomes of Laparoscopic Gastrectomy and Open Gastrectomy for Scirrhous Gastric Cancer: A Multicenter Retrospective Cohort Study.

Objective: A multicenter retrospective cohort study was performed to compare the outcomes of laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for scirrhous gastric cancer (GC) as a unique subtype also known as type 4 gastric cancer or linitis plastica. Background: Although data on the efficacy and safety of LG as an alternative to OG are emerging, the applicability of LG to scirrhous GC remains unclear. Methods: Patients with clinical type 4 GC undergoing gastrectomy at 13 hospitals from 2005 to 2015 were retrospectively reviewed. As the primary endpoint, we compared overall survival (OS) between the LG and OG groups. To adjust for confounding factors, we used multivariate Cox regression analysis for the main analyses and propensity-score matching for sensitivity analysis. Short-term outcomes and recurrence-free survival were also compared. Results: A total of 288 patients (LG, 62; OG, 226) were included in the main analysis. Postoperative complications occurred in 25.8% and 30.1%, respectively (P = 0.44). No significant difference in recurrence-free survival was observed (P = 0.72). The 5-year OS rates were 32.4% and 31.6% in the LG and OG groups, respectively (P = 0.60). The hazard ratio (LG/OG) for OS was 0.98 (95% confidence interval [CI], 0.65-1.43) in the multivariate regression analysis. In the sensitivity analyses after propensity-score matching, the hazard ratio for OS was 0.92 (95% CI, 0.58-1.45). Conclusions: Considering the hazard ratios and 95% CIs for OS, LG for scirrhous GC was not associated with worse survival than that for OG.

Laparoscopic en bloc lower mediastinal lymph node dissection via transhiatal approach for adenocarcinoma of esophagogastric junction.

INTRODUCTION: According to previous studies, transhiatal lower mediastinal lymph node (LMLN) dissection is recommended for patients with adenocarcinoma of esophagogastric junction (AEG) with esophageal involvement of <3.0 cm [1-3]. Herein, we reported our procedure and the short-term outcomes. SURGICAL PROCEDURE: The patient was placed in a supine position under general anesthesia, and five ports were placed into the upper abdomen. After radical suprapancreatic lymph node dissection, the center of the phrenic tendon was cut and each phrenic crus was retracted laterally to obtain good operative field. The ventral tissue along the lower esophagus was dissected from the pericardia. The dissection proceeded to the right atrium along the IVC. The dorsal tissue was dissected from the aorta. The remaining plate-like tissue was dissected from the pleura. Finally, the dissected tissue was peeled back from the esophagus. RESULTS: Twenty-four patients with Siewert type II/III AEG underwent this procedure at our hospital between April 2011 and December 2019. Two cases were administered with the right thoracic approach to secure proximal margin or perform anastomosis safely. All cases underwent R0 resection. Although the Clavien-Dindo grade IIIa anastomotic leakage was confirmed in two cases (8.3%), there were no complications associated with the procedure. The median number of retrieved LMLN was five (range 0-14). Two patients had metastatic LMLN. The length of esophageal involvement in patients with metastatic LMLN was longer than that in patients with nonmetastatic LMLN (26 mm vs 12.5 mm). CONCLUSION: Our procedure was safe and feasible for lymph node dissection in AEG.

Upper mediastinal lymph node dissection based on mesenteric excision in esophageal cancer surgery: confirmation by near-infrared image-guided lymphatic mapping and the impact on locoregional control.

BACKGROUND: We previously reported a novel method of mesenteric excision for esophageal cancer surgery. The esophagus, trachea, recurrent laryngeal nerves (RLNs), and surrounding lymph nodes (LNs) are contained in a common mesenterium, which we termed the "mesotracheoesophagus". In addition, near-infrared (NIR) image-guided lymphatic mapping has recently been used. The purpose of this study was to confirm the feasibility of NIR image-guided lymphatic mapping for upper mediastinal LN dissection, and to confirm the oncological feasibility of our surgical approach. METHODS: Fifteen patients with resectable esophageal cancer underwent submucosal injection of indocyanine green (ICG), and underwent robot-assisted esophagectomy. The frequency of ICG positivity in the LN basins along the RLNs, and metastatic frequency were assessed. Regarding the oncological feasibility of our thoracoscopic esophagectomy, the recurrence patterns and survival of 72 consecutive patients who underwent curative resection from 2011 to 2016 were analyzed. RESULTS: ICG-positive LN basins along the right and left RLNs were found in 12 (80% of 15) patients (3 patients positive for metastatic LNs) and 11 (73% of 15) patients (2 positive for metastatic LNs and 1 false-negative), respectively. All ICG-positive LN basins were found within the mesotracheoesophagus. The sensitivity was 5/6 (83%), and the negative predictive value was 6/7 (86%). Among the 72 patients, with a median follow-up period of 1644 days, only 3 (4.2%) patients developed locoregional recurrence. CONCLUSIONS: The NIR image-guided lymphatic mapping was feasible. Our results with no ICG-positive basins outside of the '"mesotracheoesophagus", supported our surgical approach. It might become standard, with acceptable locoregional control.

Educational application of intraoperative records from an energy device in laparoscopic gastrectomy: a preliminary report.

PURPOSE: Video review is a reliable method for surgical education in laparoscopic gastrectomy (LG), but more objective methods are still needed. The purpose of this study was to determine whether the energy device records reflected surgical competency, and thereby may improve surgical education. METHODS: A total of 16 patients who underwent LG for gastric cancer using the Thunderbeat® device were preliminarily retrospectively analyzed. This device has the function of 'intelligent tissue monitoring' (ITM), a safety assist system stopping energy output, and can record ITM detections and firing time during surgery. The number of ITM detections and firings, and the total firing time during gastrocolic ligament dissection and infrapyloric dissection were compared between trainees (n = 9 by 5 surgeons) and experts (n = 7 by 5 surgeons). The non-edited videos (n = 16) were scored, and the correlations between the scores and the records were then analyzed. RESULTS: Significantly more ITM detections, firings, and a longer total firing time were observed in trainees than in experts. The number of ITM detections and firing had negative correlations with the scores of the operation speed, the use of the non-dominant hand, and the use of an energy device. CONCLUSIONS: Our preliminary study suggested that the above described energy device records reflected surgical competency, and thereby may improve surgical education.

Appropriate traction can help identify the optimal dissectable layer for infrapyloric lymph node dissection in laparoscopic gastrectomy.

INTRODUCTION: Appropriate dissection of the infrapyloric lymph nodes (no. 6 LNs) is important in gastric cancer surgery. In laparoscopic surgery, dissection of the no. 6 LNs along the inner dissectable layer from the left side of patient has been reported. However, it is difficult for surgeons to provide appropriate traction with their left hand from the left side. To resolve this difficulty, we dissected the no. 6 LNs from the patient's right side to identify the optimal layer. We then evaluated the oncologic reliability of the layer and the safety of this procedure. METHODS: From the patient's right side, the surgeon used their left hand to provide appropriate traction when pulling the adipose tissue, including the no. 6 LNs. This exposed the optimal layer between the adipose tissue and the pancreas. To assess this maneuver, the surgical outcomes of patients who underwent laparoscopic distal gastrectomy from April 2011 to March 2013 were retrospectively analyzed. The surgical outcomes included the number of the no. 6 LNs resected, time to dissect the no. 6 LNs, incidence of pancreatic complications, and recurrence in the no. 6 LNs. RESULTS: There were 112 patients identified. The median number of the no. 6 LNs resected was five. The median time to dissect the no. 6 LNs was 14 minutes. Four patients developed pancreatic fistula, and another four patients developed intra-abdominal abscess. There was no recurrence in the no. 6 LNs. CONCLUSION: The optimal layer was oncologically reliable, and these procedures were safe.