Comparison of the survival outcomes between retrocolic and antecolic Roux-en-Y reconstruction after gastrectomy for gastric cancer.

Background: There are two methods of Roux-en-Y (RY) reconstruction after gastrectomy: the antecolic route (ACR) and retrocolic route (RCR). There is no evidence to support that the ACR achieves comparable long-term survival. Methods: This was a multi-center historical cohort study. Patients diagnosed with clinical T3/4a and any N stage who underwent open gastrectomy and R0 resection for gastric adenocarcinoma between January 2006 and December 2012 were enrolled. The primary outcome was the hazard ratio of ACR for overall survival, with adjustment for confounding factors by propensity score matching, and a Cox proportional hazards model. Results: A total of 1758 eligible patients were identified from the database. After matching, 410 patients in the ACR and RCR groups were included in the final analysis. The adjusted hazard ratio (95% CI) for ACR was 1.148 (0.870-1.492). The five-year survival rates in the ACR and RCR groups were 74.3% (69.5-78.4) and 77.3% (72.3-81.2), respectively. The short-term surgical outcomes of the two groups did not differ to a statistically significant extent. Conclusion: The route used to lift the jejunum in RY reconstruction did not affect the incidence of long-term survival or postoperative complications. The ACR and RCR are both acceptable options for RY reconstruction during gastric cancer surgery.

Definitive chemoradiotherapy induces T-cell-inflamed tumor microenvironment in unresectable locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Chemoradiotherapy (CRT) modulates the tumor immune microenvironment of multiple cancer types, including esophageal cancer, which potentially induces both immunogenicity and immunosuppression by upregulating the presentation of tumor-specific antigens and immune checkpoint molecules in tumors, respectively. The prognostic effects of immune modification by CRT in esophageal squamous cell carcinoma (ESCC) remain controversial because of the lack of detailed immunological analyses using paired clinical specimens before and after CRT. We aimed to clarify the immunological changes in the tumor microenvironment caused by CRT and elucidate the predictive importance of clinical response and prognosis and the rationale for the necessity of subsequent programmed cell death protein 1 (PD-1) inhibitor treatment. METHODS: In this study, we performed a comprehensive immunological analysis of paired biopsy specimens using multiplex immunohistochemistry before and after CRT in patients with unresectable locally advanced ESCC. RESULTS: CRT significantly increased the intra-tumoral infiltration and PD-1 expression of CD8+ T cells and conventional CD4+ T cells but decreased those of regulatory T cells and the accumulation of tumor-associated macrophages. Multivariate analysis of tumor-infiltrating T-cell phenotypes revealed that the density of PD-1+CD8+ T cells in the tumor after CRT could predict a confirmed complete response and favorable survival. CONCLUSIONS: This study showed that CRT improved the immunological characteristics of unresectable locally advanced ESCC and identified the density of PD-1+CD8+ T cells as a predictive factor for prognosis. This finding supports the rationale for the necessity of subsequent PD-1 inhibitor treatment.

Feasibility of laparoscopic/robot-assisted surgery for Borrmann type 4 gastric cancer: a comparison study with conventional open surgery.

BACKGROUND: Laparoscopic surgery for early gastric cancer is regarded as a standard of care because of robust evidences obtained by several phase-III trials. Furthermore, the efficacy of laparoscopic radical surgery for advanced gastric cancer has been also reported. Meanwhile, the feasibility of laparoscopic surgery for Bormann type 4 gastric cancer, special type with unfavorable prognosis, remains unclear since excluded from eligibility of these trials. METHODS: This study included 100 patients with type 4 gastric cancer who underwent laparoscopic/robot-assisted (minimally invasive surgery (MIS) group; n = 32) or open (Open group; n = 68) curative surgery between 2008 and 2021. After propensity score matching, 30 patients in each group were extracted for analysis. Clinical data, including surgical and midterm survival outcomes, were retrospectively compared between the two groups. RESULTS: Incidences of postoperative complication (≥ Clavien-Dindo grade III) were recorded in 23.3% in the MIS group and 13.3% in the Open group, but no statistical significance was demonstrated (P = 0.50). The 3-year overall survival rate in the MIS group was better than that in the Open group (80.2% vs. 53.5%, log-rank, P = 0.03). The trend of recurrence site was similar. Multivariate analysis showed that adjuvant chemotherapy was an independent favorable prognostic factor (hazard ratio, 0.33, 95% confidence interval 0.11-0.93) for overall survival. MIS was indicated as a favorable prognostic factor (hazard ratio, 0.39, 95% confidence interval 0.39-1.07), but without statistical difference. CONCLUSION: While multidisciplinary treatment is mainstay of treatment because of the poor prognosis of this disease, minimally invasive surgery may play an important role in treatment if appropriate patient selection is done. Further analyses with larger sample size are necessary to reach a final conclusion regarding oncological efficacy.

Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).

BACKGROUND: This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis. METHODS: Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006. RESULTS: This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively. CONCLUSIONS: Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.

A nonrandomized controlled trial: long-term outcomes of LATG/LAPG for cStage I gastric cancer: Japan Clinical Oncology Group Study JCOG1401.

BACKGROUND: A previous report confirmed the safety of laparoscopy-assisted total and proximal gastrectomies (LATG and LAPG) (JCOG1401). This report demonstrates the 5-year relapse-free survival (RFS) and overall survival (OS) after long-term follow-up to confirm the efficacy of these surgical methods as key secondary endpoints for cStage I gastric cancer. METHODS: This study enrolled patients who had histologically proven gastric adenocarcinoma and were diagnosed with clinical T1N0, T1N(+), or T2N0 tumors according to the 14th edition of the Japanese Classification of Gastric Carcinoma (3rd English edition). RESULTS: Between April 2015 and February 2017, 246 patients were enrolled, although one patient was excluded because of misregistration. Meticulous follow-up was continued for > 5 years for each patient, and the data were analyzed in March 2022. The 5-year RFS was 90.0% (95% confidence interval [CI] 85.5-93.2%), and the 5-year OS was 91.2% (95% CI 86.9-94.2%) in all enrolled patients. Grade 3 or 4 late postoperative complications were detected in 12.7% of patients. CONCLUSIONS: This single-arm study showed that the long-term outcomes of LATG/LAPG for cStage I gastric cancer were acceptable, which is considered one of the standard treatments when performed by experienced surgeons. Trail registration UMIN000017155 ( http://www.umin.ac.jp/ctr/ ).

Automatic surgical phase recognition-based skill assessment in laparoscopic distal gastrectomy using multicenter videos.

BACKGROUND: Gastric surgery involves numerous surgical phases; however, its steps can be clearly defined. Deep learning-based surgical phase recognition can promote stylization of gastric surgery with applications in automatic surgical skill assessment. This study aimed to develop a deep learning-based surgical phase-recognition model using multicenter videos of laparoscopic distal gastrectomy, and examine the feasibility of automatic surgical skill assessment using the developed model. METHODS: Surgical videos from 20 hospitals were used. Laparoscopic distal gastrectomy was defined and annotated into nine phases and a deep learning-based image classification model was developed for phase recognition. We examined whether the developed model's output, including the number of frames in each phase and the adequacy of the surgical field development during the phase of supra-pancreatic lymphadenectomy, correlated with the manually assigned skill assessment score. RESULTS: The overall accuracy of phase recognition was 88.8%. Regarding surgical skill assessment based on the number of frames during the phases of lymphadenectomy of the left greater curvature and reconstruction, the number of frames in the high-score group were significantly less than those in the low-score group (829 vs. 1,152, P < 0.01; 1,208 vs. 1,586, P = 0.01, respectively). The output score of the adequacy of the surgical field development, which is the developed model's output, was significantly higher in the high-score group than that in the low-score group (0.975 vs. 0.970, P = 0.04). CONCLUSION: The developed model had high accuracy in phase-recognition tasks and has the potential for application in automatic surgical skill assessment systems.

Surgical Techniques and Related Perioperative Outcomes After Robot-assisted Minimally Invasive Gastrectomy (RAMIG): Results From the Prospective Multicenter International Ugira Gastric Registry.

OBJECTIVE: To gain insight in global practice of RAMIG and evaluated perioperative outcomes using an international registry. BACKGROUND: The techniques and perioperative outcomes of robot-assisted minimally invasive gastrectomy (RAMIG) for gastric cancer vary substantially in literature. METHODS: Prospectively registered RAMIG-cases for gastric cancer (≥10 per center) were extracted from 25 centers in Europe, Asia and South-America. Techniques for the resection, reconstruction, anastomosis and lymphadenectomy were analyzed, and related to perioperative surgical and oncological outcomes. Complications were uniformly defined by the Gastrectomy Complications Consensus Group. RESULTS: Between 2020-2023, 759 patients underwent total (n=272), distal (n=465) or proximal (n=22) gastrectomy (RAMIG). After total gastrectomy with Roux-en-Y-reconstruction, anastomotic leakage rates were 8% with hand-sewn (n=9/111) and 6% with linear stapled anastomoses (n=6/100). After distal gastrectomy with Roux-en-Y (67%) or Billroth-II-reconstruction (31%), anastomotic leakage rates were 3% with linear stapled (n=11/433) and 0% with hand-sewn anastomoses (n=0/26). Extent of lymphadenectomy consisted of D1+ (28%), D2 (59%) or D2+ (12%). Median nodal harvest yielded 31 nodes [IQR 21-47] after total and 34 nodes [IQR 24-47] after distal gastrectomy. R0-resection rates were 93% after total and 96% distal gastrectomy. Hospital stay was 9 days after total and distal gastrectomy, and was 3 days shorter without perianastomotic drains versus routine drain placement. Postoperative 30-day mortality was 1%. CONCLUSIONS: This large multicenter study provided a worldwide overview of current RAMIG-techniques with their respective perioperative outcomes. These outcomes demonstrated high surgical quality, set a quality standard for RAMIG and can be considered an international reference for surgical standardization.

Randomized controlled phase III trial to investigate superiority of robot-assisted gastrectomy over laparoscopic gastrectomy for clinical stage T1-4aN0-3 gastric cancer patients (JCOG1907, MONA LISA study): a study protocol.

BACKGROUND: Laparoscopic gastrectomy (LG) is considered a standard treatment for clinical stage I gastric cancer. Nevertheless, LG has some drawbacks, such as motion restriction and difficulties in spatial perception. Robot-assisted gastrectomy (RG) overcomes these drawbacks by using articulated forceps, tremor-filtering capability, and high-resolution three-dimensional imaging, and it is expected to enable more precise and safer procedures than LG for gastric cancer. However, robust evidence based on a large-scale randomized study is lacking. METHODS: We are performing a randomized controlled phase III study to investigate the superiority of RG over LG for clinical T1-2N0-2 gastric cancer in terms of safety. In total, 1,040 patients are planned to be enrolled from 46 Japanese institutions over 5 years. The primary endpoint is the incidence of postoperative intra-abdominal infectious complications, including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess of Clavien-Dindo (CD) grade ≥ II. The secondary endpoints are the incidence of all CD grade ≥ II and ≥ IIIA postoperative complications, the incidence of CD grade ≥ IIIA postoperative intra-abdominal infectious complications, relapse-free survival, overall survival, the proportion of RG completion, the proportion of LG completion, the proportion of conversion to open surgery, the proportion of operation-related death, and short-term surgical outcomes. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in January 2020. Approval from the institutional review board was obtained before starting patient enrollment in each institution. Patient enrollment began in March 2020. We revised the protocol to expand the eligibility criteria to T1-4aN0-3 in July 2022 based on the results of randomized trials of LG demonstrating non-inferiority of LG to open surgery for survival outcomes in advanced gastric cancer. DISCUSSION: This is the first multicenter randomized controlled trial to confirm the superiority of RG over LG in terms of safety. This study will demonstrate whether RG is superior for gastric cancer. TRIAL REGISTRATION: The protocol of JCOG1907 was registered in the UMIN Clinical Trials Registry as UMIN000039825 ( http://www.umin.ac.jp/ctr/index.htm ). Date of Registration: March 16, 2020. Date of First Participant Enrollment: April 1, 2020.

[Treatment Strategy for Oligometastatic Gastric Cancer].

Oligometastases are generally defined as a small number of metastases(2-3 or less)in 1 or 2 organs. Oligometastases are rare in gastric cancer because they are often associated with peritoneal dissemination, but gastric cancer patients experience a relatively high incidence of para-aortic lymph node and liver metastases in particular. The Sixth Edition of the Japanese Gastric Cancer Treatment Guidelines weakly recommends surgical resection after medical therapy for a small number of para-aortic lymph node metastases confined to No. 16a2/b1 and a single liver metastasis in the absence of other non-curative resection factors. In Japan, the common treatment strategy is surgical resection after drug therapy, often with the addition of adjuvant chemotherapy after surgery as well. Preoperative drug therapy is generally administered for 3-4 months. Surgical resection has been shown to be relatively safe in experienced centers. Prospective clinical trials are underway in Japan and overseas to establish a higher level of evidence.

Evaluating the identification of the extent of gastric cancer by over-1000 nm near-infrared hyperspectral imaging using surgical specimens.

Significance: Determining the extent of gastric cancer (GC) is necessary for evaluating the gastrectomy margin for GC. Additionally, determining the extent of the GC that is not exposed to the mucosal surface remains difficult. However, near-infrared (NIR) can penetrate mucosal tissues highly efficiently. Aim: We investigated the ability of near-infrared hyperspectral imaging (NIR-HSI) to identify GC areas, including exposed and unexposed using surgical specimens, and explored the identifiable characteristics of the GC. Approach: Our study examined 10 patients with diagnosed GC who underwent surgery between 2020 and 2021. Specimen images were captured using NIR-HSI. For the specimens, the exposed area was defined as an area wherein the cancer was exposed on the surface, the unexposed area as an area wherein the cancer was present although the surface was covered by normal tissue, and the normal area as an area wherein the cancer was absent. We estimated the GC (including the exposed and unexposed areas) and normal areas using a support vector machine, which is a machine-learning method for classification. The prediction accuracy of the GC region in every area and normal region was evaluated. Additionally, the tumor thicknesses of the GC were pathologically measured, and their differences in identifiable and unidentifiable areas were compared using NIR-HSI. Results: The average prediction accuracy of the GC regions combined with both areas was 77.2%; with exposed and unexposed areas was 79.7% and 68.5%, respectively; and with normal regions was 79.7%. Additionally, the areas identified as cancerous had a tumor thickness of >2 mm. Conclusions: NIR-HSI identified the GC regions with high rates. As a feature, the exposed and unexposed areas with tumor thicknesses of >2 mm were identified using NIR-HSI.

Artificial Intelligence in Surgery and Its Potential for Gastric Cancer.

Artificial intelligence (AI) has made significant progress in recent years, and many medical fields are attempting to introduce AI technology into clinical practice. Currently, much research is being conducted to evaluate that AI can be incorporated into surgical procedures to make them safer and more efficient, subsequently to obtain better outcomes for patients. In this paper, we review basic AI research regarding surgery and discuss the potential for implementing AI technology in gastric cancer surgery. At present, research and development is focused on AI technologies that assist the surgeon's understandings and judgment during surgery, such as anatomical navigation. AI systems are also being developed to recognize in which the surgical phase is ongoing. Such a surgical phase recognition systems is considered for effective storage of surgical videos and education, in the future, for use in systems to objectively evaluate the skill of surgeons. At this time, it is not considered practical to let AI make intraoperative decisions or move forceps automatically from an ethical standpoint, too. At present, AI research on surgery has various limitations, and it is desirable to develop practical systems that will truly benefit clinical practice in the future.

Advantages of robotic gastrectomy for overweight patients with gastric cancer: a comparison study of robotic gastrectomy and conventional laparoscopic gastrectomy.

PURPOSE: A high body mass index (BMI) generally increases the risk of postoperative complications because of the intraperitoneal adipose tissue. Robotic gastrectomy (RG) decreases the surgical difficulty of conventional laparoscopic gastrectomy (LG) for these patients. We conducted the present study to identify the advantages of RG over LG for overweight patients. METHODS: We reviewed clinical data on patients who underwent either LG or RG at the National Cancer Center Hospital East between January, 2014 and May, 2022. RESULTS: The 1298 patients eligible patients were divided into a non-overweight cohort (n = 996) (LG, n = 818; RG, n = 178) and an overweight cohort (n = 302) (LG, n = 250; RG, n = 52) according to a BMI cut-off of 25 kg/m2. In the overweight cohort, the RG group had a lower incidence of grade ≥ III postoperative complications (0.0 vs. 8.8%, p = 0.01) and grade ≥ II postoperative complications (11.5 vs. 22.0%, p = 0.12) than the LG group. Multivariate analysis identified that RG was significantly associated with a lower incidence of grade ≥ II postoperative complications in the overweight cohort (odds ratio, 0.33; 95% confidence interval, 0.12-0.87; p = 0.02). CONCLUSIONS: RG may reduce the risk of postoperative complications, compared with conventional LG, in overweight patients.

Impact of Programmed Death-Ligand 1 Expression on Mismatch Repair Deficiency and Epstein-Barr Virus Status on Survival Outcomes in Patients with Stage II/III Gastric Cancer After Surgery.

BACKGROUND: The aim of this study was to investigate the prognostic impact of mismatch repair (MMR) status, programmed death-ligand 1 (PD-L1) expression, and Epstein-Barr virus (EBV) status in stage II/III gastric cancer after surgery. METHODS: This study included 679 patients diagnosed with pathological stage II/III gastric cancer who underwent curative gastrectomy followed by adjuvant chemotherapy (AC) or observation between 2007 and 2015. Clinical outcomes were retrospectively reviewed and compared with stratification by AC and other clinicopathological factors. RESULTS: Patients were divided into AC (n = 484) or surgery alone (SA; n = 195) groups and were further stratified by MMR and EBV status: MMR-deficient (DMMR) and MMR-proficient (PMMR) groups. Comparing the AC-DMMR group versus the AC-PMMR group, 5-year overall survival was 92.0% versus 74.0% (log-rank p < 0.01), and comparing the SA-DMMR group versus the SA-PMMR group, 5-year overall survival was 71.1% versus 73.7% (log-rank p = 0.89). DMMR (hazard ratio 0.25, 95% confidence interval 0.07-0.81) was identified as an independent prognostic factor in the AC group but not in the SA group. In the subgroup analysis, PD-L1-negative patients among the EBV-positive patients or in the DMMR group had a poor prognosis in both the AC and SA groups. The prognosis of the PMMR and EBV-negative patients was similar regardless of PD-L1 expression. CONCLUSIONS: DMMR was associated with a favorable prognosis in stage II/III gastric cancer after surgery and adjuvant therapy. PD-L1 expression may affect the prognosis of DMMR and EBV-positive gastric cancer.

Five-Year Survival Outcomes of Laparoscopy-Assisted vs Open Distal Gastrectomy for Advanced Gastric Cancer: The JLSSG0901 Randomized Clinical Trial.

Importance: Evidence of implementation of laparoscopic gastrectomy for locally advanced gastric cancer is currently insufficient, as the primary end point in previous prospective studies was evaluated at a median follow-up time of 3 years. More robust evidence is necessary to verify noninferiority of laparoscopic gastrectomy. Objective: To compare 5-year survival outcomes between laparoscopy-assisted distal gastrectomy (LADG) and open distal gastrectomy (ODG) with D2 lymph node dissection for locally advanced gastric cancer. Design, Setting, and Participants: This was a multicenter, open-label, noninferiority, prospective randomized clinical trial. Between November 26, 2009, and July 29, 2016, eligible patients with histologically proven gastric carcinoma from 37 institutes in Japan were enrolled. Two interim analyses and final analysis were performed in October 2014, May 2018, and November 2021, respectively. Interventions: Patients were randomly assigned (1:1) to either the ODG or LADG group. The procedures were performed exclusively by qualified surgeons. Main Outcomes and Measures: The primary end point was 5-year relapse-free survival, and the noninferiority margin for the hazard ratio (HR) was set at 1.31. The secondary end points were 5-year overall survival and safety. Results: A total of 502 patients were included in the full-analysis set: 254 (50.6%) in the ODG group and 248 (49.4%) in the LADG group. Patients in the ODG group had a median (IQR) age of 67 (33-80) years and included 168 males (66.1%). Patients in the LADG group had a median (IQR) age of 64 (34-80) years and included 169 males (68.1%). No significant differences were observed in severe postoperative complications between the 2 groups in the safety analysis (ODG, 4.7% [11 of 233] vs LADG, 3.5% [8 of 227]; P = .64). The median (IQR) follow-up for all patients after randomization was 67.9 (60.3-92.0) months. The 5-year relapse-free survival was 73.9% (95% CI, 68.7%-79.5%) and 75.7% (95% CI, 70.5%-81.2%) for the ODG and LADG groups, respectively, and the HR was 0.96 (90% CI, 0.72-1.26; noninferiority 1-sided P = .03). Further, no significant difference was observed in overall survival time between the 2 groups, and the HR was 0.83 (95% CI, 0.57-1.21; P = .34). The pattern of recurrence was similar between the 2 groups. Conclusions and Relevance: Results of this study show that on the basis of 5-year follow-up data, LADG with D2 lymph node dissection for locally advanced gastric cancer, when performed by qualified surgeons, was proved noninferior to ODG. This laparoscopic approach could become a standard treatment for locally advanced gastric cancer. Trial Registration: UMIN Clinical Trial Registry: UMIN000003420.

Requirement of image standardization for AI-based macroscopic diagnosis for surgical specimens of gastric cancer.

PURPOSE: The pathological diagnosis of surgically resected gastric cancer involves both a macroscopic diagnosis by gross observation and a microscopic diagnosis by microscopy. Macroscopic diagnosis determines the location and stage of the disease and the involvement of other organs and surgical margin. Lesion recognition is, thus, an important diagnostic step that requires a skilled pathologist. Nonetheless, artificial intelligence (AI) technologies could allow even inexperienced doctors and laboratory technicians to examine surgically resected specimens without the need for pathologists. However, organ imaging conditions vary across hospitals, and an AI algorithm created in one setting may not work properly in another. Thus, we identified and standardized factors affecting the quality of pathological macroscopic images, which could further affect lesion identification using AI. METHODS: We examined necessary image standardization for developing cancer detection AI for surgically resected gastric cancer by changing the following imaging conditions: focus, resolution, brightness, and contrast. RESULTS: Regarding focus, brightness, and contrast, the farther away the test data were from the training macro-image, the less likely the inference was to be correct. Little change was observed for resolution, even with differing conditions for the training and test data. Regarding focus, brightness, and contrast, there were conditions appropriate for AI. Contrast, in particular, was far from the conditions appropriate for humans. CONCLUSION: Standardizing focus, brightness, and contrast is important in the development of AI methodologies for lesion detection in surgically resected gastric cancer. This standardization is essential for AI to be implemented across hospitals.

Complete response to definitive chemoradiotherapy in unresectable locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Although definitive chemoradiotherapy (CRT) is the standard therapy for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), poor survival has been reported. Although the complete response (CR) rate is strongly correlated with good prognosis, the predictive factors for CR have not been elucidated. METHODS: This registry study aimed to identify predictors of CR to definitive CRT in patients with unresectable locally advanced ESCC. "Unresectable" was defined as the primary lesion invading unresectable adjacent structures such as the aorta, vertebral body, and trachea (T4b), or the regional and/or supraclavicular lymph nodes invading unresectable adjacent structures (LNT4b). RESULTS: Overall, 175 patients who started definitive CRT between January 2013 and March 2020 were included. The confirmed CR (cCR) rate was 24% (42/175). The 2-year progression-free survival (PFS) and overall survival (OS) rates of cCR cases vs. non-cCR cases were 59% vs. 2% (log-rank p < 0.001) and 90% vs. 31% (log-rank p < 0.001), with a median follow-up period of 18.5 and 40.5 months, respectively. Multivariate analysis of clinicopathological factors revealed that tumor length ≥ 6 cm [odds ratio (OR) 0.446; 95% CI 0.220-0.905; p = 0.025] was a predictor of cCR. CONCLUSIONS: Favorable PFS and OS rates were observed in patients with cCR. Tumor length was a predictive factor for cCR.

Survival outcomes of laparoscopic versus open total gastrectomy with nodal dissection for gastric cancer in a high-volume Japanese center: A propensity score-matched analysis.

Aim: To compare the survival outcomes of laparoscopic total gastrectomy (LTG) with those of open total gastrectomy (OTG) in gastric cancer. Methods: Using an in-house database, this single-center study reviewed clinical data for patients who underwent surgery for gastric adenocarcinoma in 2008-2018. The patients were divided into an LTG group and an OTG group. Results: Data for 638 patients were screened. After exclusions, 580 patients (LTG, n = 212; OTG, n = 368) were enrolled. Noting that the OTG group included more advanced tumors, 1:1 propensity score matching was implemented to reduce any selection bias, leaving 326 patients (LTG, n = 163; OTG, n = 163; pStage I/II/III = 147/87/92) for further analysis. The operation time was longer and blood loss was less in the LTG group. The postoperative hospital stay was shorter in the LTG group than in the OTG group (9 d vs 10 d；P = .040). There was no significant difference in the incidence of grade III or worse postoperative complications (8.9% vs 11.0%). Five-year overall survival was better in the LTG group (84.9% vs 73.5%; P = .0010, log-rank test), but there was no significant difference in overall survival according to pStage (I, 93.0% vs 89.0%; II, 85.8% vs 77.5%; III, 64.1% vs 52.5%). There was a similar trend in relapse-free survival. Distribution of recurrence sites was comparable. Conclusion: LTG may provide survival outcomes similar to those of OTG when performed by an experienced surgical team. Further evidence is required for final conclusions, especially regarding its efficacy for stage II/III.

Evaluating the efficacy of post-operative chemotherapy after curative resection of stage IV gastric cancer with synchronous oligo metastasis: a multicenter retrospective study.

BACKGROUND: Surgical resection of oligo-metastasis in gastric cancer (GC) is weakly recommended for patients without other incurable factors in the Japanese GC Treatment Guidelines. While post-operative chemotherapy is the standard treatment in patients with stage II or III GC, its efficacy for resected stage IV GC is unclear. This study aimed to evaluate the efficacy of post-operative chemotherapy after curative resection of GC with oligo-metastasis. METHODS: We retrospectively reviewed the medical records of patients with GC who were diagnosed with synchronous oligo-metastasis at 20 institutions in Japan between 2007 and 2012. The selection criteria were: adenocarcinoma, stage IV with oligo-metastasis at liver or lymph node without other distant metastasis, curative resection including synchronous oligo-metastasis, and no prior treatment of GC before surgery. RESULTS: A total of 110 patients were collected. Of the 94 eligible patients, 84 underwent gastrectomy with surgical resection of oligo-metastasis (39 [41%] liver metastasis and 55, [59%] distant lymph node metastasis), followed by post-operative chemotherapy with S-1 (S1: n = 55), S1 plus cisplatin (CS: n = 22), or Others (n = 7). Moreover, 10 patients did not receive post-operative chemotherapy (Non-Cx). The median overall survival (OS) was 35.2 and 11.1 months in the post-operative chemotherapy and Non-Cx groups (hazard ratio, 3.56; 95% confidence interval, 1.74-7.30; p < 0.001), respectively. In multivariable analysis, Non-Cx and age over 70 years were identified as poor prognostic factors for OS (p < 0.05). CONCLUSIONS: Curative resection followed by post-operative chemotherapy in patients with GC with synchronous oligo-metastasis showed favorable survival.

Cancer-associated fibroblast-dependent and -independent invasion of gastric cancer cells.

PURPOSE: Cancer cells are known to exhibit a cancer-associated fibroblast (CAF)-dependent invasive mode in the presence of CAFs. The purpose of this study was to investigate whether intrinsic factors of gastric cancer cells influence the CAF-dependent invasive mode of cancer cells. METHODS: We observed dynamic movement of CAFs, and cancer cells, by time-lapse imaging of 2-D and 3-D collagen invasion models, and evaluated invasion modes of gastric cancer cell lines (MKN-7, MKN-45, and HSC44PE). We further examined whether modification of invasive capacity of CAFs can alter invasive mode of MKN-7, and HSC44PE cells. RESULTS: When MKN-7 and MKN-45 cells were co-cultured with CAFs, CAFs first invade collagen matrix followed by cancer cells (CAF-dependent invasion), whereas HSC44PE cells invaded collagen matrix independent of CAFs' invasion. Overexpression or suppression of podoplanin in CAFs, respectively, increased or decreased the invasive capacity of CAFs, and significantly increased or decreased the number of invading MKN-7 cells, respectively. CAFs overexpressing a podoplanin mutant, lacking the cytoplasmic domain, had significantly reduced invasive capacity, compared to CAFs overexpressing wild-type podoplanin, and it also reduced the number of invading MKN-7 cells significantly. When HSC44PE cells, and CAFs were co-cultured, changes in the podoplanin expression in CAFs similarly altered the invasive capacity of CAFs, but it did not affect the number of invading HSC44PE cells. CONCLUSIONS: These results indicate that in presence of CAFs, gastric cancer cells exhibit both CAF-dependent and -independent modes of invasion, the determinants of which may depend on the intrinsic properties of the gastric cancer cells.