Novel reconstruction using pedicled ileocolic interposition with intrathoracic esophago-ileal anastomosis after distal esophagectomy for esophagogastric junction cancer: A report of two cases.

There is no optimal reconstruction after radical distal esophagectomy for cancers of the esophagogastric junction. We designed a novel reconstruction technique using pedicled ileocolic interposition with intrathoracic anastomosis between the esophagus and the elevated ileum. Two patients underwent the surgery. Case 1 was a 70-year-old man with esophagogastric junction adenocarcinoma with 3 cm of esophageal invasion. Case 2 was a 70-year-old man with squamous cell carcinoma of the esophagogastric junction; the epicenter of which was located just at the junction. These two patients underwent radical distal esophagectomy and pedicled ileocolic interposition with intrathoracic anastomosis. They were discharged on postoperative days 17 and 14, respectively, with no major complication. Pedicled ileocolic interposition is characterized by sufficient elevation and perfusion of the ileum, which is fed by the ileocolic artery and vein. As a result, we can generally adapt this reconstruction method to most curable esophagogastric junction cancers.

Clinical impact of skeletal muscle mass change during the neoadjuvant chemotherapy period in patients with gastric cancer: An ancillary study of JCOG1002.

BACKGROUND: Recent studies have revealed that sarcopenia is associated with postoperative complications and poor prognosis. Although neoadjuvant chemotherapy is a promising treatment for gastric cancer, its toxicity may lead to the loss of skeletal muscle mass. This study investigates the changes in skeletal muscle mass during neoadjuvant chemotherapy and its clinical impact on patients with locally advanced gastric cancer. METHODS: Fifty patients who completed two courses of neoadjuvant chemotherapy followed by surgery were included. Skeletal muscle mass was measured using computed tomography images before and after chemotherapy. The proportion of skeletal muscle mass change (%SMC) during neoadjuvant chemotherapy and its cutoff value was explored using the receiver operating characteristic for the overall survival of patients undergoing R0 resection. Risk factors of skeletal muscle mass loss were also evaluated. RESULTS: Overall, 64% of patients had skeletal muscle mass loss during neoadjuvant chemotherapy (median %SMC -3.4%; range: -18.9% to 10.3%). Multivariable analysis identified older age (≥70 years) as an independent predictor of skeletal muscle mass loss (mean [95% confidence interval]: -4.70% [-8.83 to -0.58], p = 0.026). Among 43 patients undergoing R0 resection, %SMC <-6.9% was an independent poor prognostic factor for overall survival (hazard ratio, 11.53; 95% confidence interval, 2.78-47.80) and relapse-free survival (hazard ratio 4.54, 95% confidence interval 1.50-13.81). CONCLUSIONS: Skeletal muscle mass loss occurs frequently during neoadjuvant chemotherapy for locally advanced gastric cancer and could adversely affect survival outcomes.

Chemotherapy and COVID-19 Vaccination in Patients With Gastrointestinal Cancer.

BACKGROUND/AIM: Multiple doses of vaccines against the coronavirus disease (COVID-19) provide patients with cancer the opportunity to continue cancer treatment. This study investigated the safety and efficacy of COVID-19 vaccination in patients with cancer and the optimal timing of vaccination during chemotherapy. PATIENTS AND METHODS: A total of 131 patients with gastrointestinal (GI) cancer who received two doses of the COVID-19 vaccine were included in this study. This study combined two cohorts: an evaluation cohort of 79 patients receiving chemotherapy and a control cohort of 52 patients under follow-up after radical surgery. None of the patients had any history of COVID-19. Treatment- and vaccine-related adverse events (AEs) were recorded through outpatient interviews and self-reports. RESULTS: In the evaluation cohort, 62 patients (78.4%) experienced vaccine-related AEs after the first dose, and 62 patients (78.4%) experienced vaccine-related AEs with an increased rate of fever and fatigue after the second dose. In the control cohort, vaccine-related AEs occurred in 28 (53.8%) patients after the first dose and in 37 (71.2%) patients after the second dose, with increased fever and fatigue after the second dose. Of the 79 patients, 49 received chemotherapy before vaccination. Twelve patients (24.5%) changed their treatment schedule: four for safety reasons, four for myelosuppression, and four for convenience. Three patients discontinued the treatment because of disease progression. CONCLUSION: Systemic chemotherapy in patients with GI cancer does not have a markedly negative effect on COVID-19 vaccination, resulting in manageable vaccine-related AEs, and minimizing the need for treatment schedule changes.

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.

Effects of a force feedback function in a surgical robot on the suturing procedure.

BACKGROUND: Currently, widely used robotic surgical systems do not provide force feedback. This study aimed to evaluate the impact and benefits of a force feedback function on the suturing procedure. METHODS: Twenty surgeons were recruited and divided into young (Y-group, n = 11) and senior (S-group, n = 9) groups, based on their years of surgical experience. The effect of the force feedback function on suturing quality was evaluated using an objective assessment system (A-LAP mini, Kyoto Kagaku Co., Ltd., Kyoto, Japan). Each participant completed the suturing task on intestinal model sheets with the robotic contact force feedback on and off. The task accomplishment time (s), maximal force (Newton, N) applied to the robotic forceps, and quality of suturing (assessed by A-LAP mini) were recorded as performance parameters. RESULTS: In total, the maximal force applied to the robotic forceps was significantly decreased with the robotic force feedback switched on (median [interquartile range]: 2.8 N (2.3-3.2)) as compared with when the feedback was switched off (3.4 N (2.7-4.0), P < 0.001). The contact force feedback function did not affect the objectively assessed suturing score (18 points (17.7-19.0) versus 18 points (17.0-19.0), P = 0.421). The contact force feedback function slightly shortened the task accomplishment time in the Y-group (552.5 s (466.5-832) versus 605.5 s (476.2-689.7), P = 0.851) but not in the S-group (566 s (440.2-703.5) versus 470.5 s (419.7-560.2), P = 0.164). CONCLUSIONS: With the contact force feedback function, the suturing task was completed with a smaller maximal force, while maintaining the quality of suturing. Because the benefits are more apparent in young surgeons, robots with the contact force feedback function will facilitate the educational process in novice surgeons.

Neoadjuvant chemotherapy for locally advanced gastric cancer in Japan: Consensus meeting at the 77th general meeting of the Japanese Society of Gastroenterological Surgery.

Treatment strategy for locally advanced gastric cancer differs worldwide. Neoadjuvant chemotherapy (NAC) is considered one of the promising treatment options for locally advanced gastric cancer, even in Japan, and clinical trials have been conducted or are ongoing. A consensus meeting was organized at the 77th general meeting of the Japanese Society of Gastroenterological Surgery in 2022, in which the current status and future prospects of NAC for locally advanced gastric cancer were discussed. Participants at the meeting looked forward to the results of the JCOG1509 trial, providing solid evidence regarding NAC. The optimal indications and regimens for NAC were also debated. Patients with cStage III gastric cancer are the main targets of NAC in Japan, and a doublet regimen of S-1 and oxaliplatin was preferred by the participants. However, the feasibility of a triplet regimen with S-1, oxaliplatin, and docetaxel, and that with 5-FU, leucovorin, oxaliplatin, and docetaxel has been demonstrated, and these could become treatment options in Japan. Other points of discussion include perioperative chemotherapy to avoid peritoneal recurrence and for patients with dMMR/MSI-high tumors. The panel regarded NAC as a promising treatment option, and NAC will become the standard treatment for cStage III gastric cancer in Japan if an ongoing clinical trial successfully demonstrates its efficacy.

Comparison of short-term outcomes between robot-assisted and laparoscopic rectal surgery for rectal cancer: A propensity score-matched analysis using the Japanese Nationwide diagnosis procedure combination database.

Background: The use of robot-assisted surgery for rectal cancer is increasing, but its short-term results remain unclear. We compared the short-term outcomes of robot-assisted and laparoscopic surgery for rectal cancer using a nationwide inpatient database. Methods: We analyzed patients registered in the Japanese Diagnosis Procedure Combination database who underwent robot-assisted or laparoscopic surgery for rectal cancer from April 2018 to March 2020. Postoperative complication rates, anesthesia time, length of hospital stay, and cost were compared using propensity score matching for low anterior resection (LAR), high anterior resection (HAR), and abdominoperineal resection (APR). Results: Among 38 090 rectal cancer cases, 1992 LAR, 357 HAR, and 310 APR pairs were generated by propensity score matching and analyzed. Anesthesia time was longer for robot-assisted surgery compared with laparoscopic surgery (LAR: 388.6 vs. 452.8 min, p < 0.001; HAR: 300.9 vs. 393.5 min, p < 0.001; APR: 4478.5 vs. 533.5 min, p < 0.001). Robot-assisted surgery was associated with significantly shorter hospital stay for LAR (22.3 vs. 20.0 days, p < 0.001) and APR (29.2 vs. 25.9 days, p = 0.029). Total costs for LAR were significantly lower for robot-assisted surgery (2031511.6 vs. 1955216.6 JPY, p < 0.001). The complication rates for robot-assisted surgery tended to be fewer than laparoscopic surgery for all procedures, but the differences were not significant. Conclusions: Although the anesthesia time was longer for robot-assisted surgery, the procedure resulted in shorter hospital stay for LAR and APR, and lower costs for LAR compared with laparoscopic surgery. Robot-assisted surgery can thus help to reduce costs and can be performed safely.

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.

Clinical significance of Bacteroides fragilis as a potential prognostic factor in colorectal cancer.

INTRODUCTION: Bacteroides fragilis (B. fragilis) is considered to act in an anti-inflammatory manner on the intestinal tract. On the contrary, enterotoxigenic B. fragilis (ETBF), a subtype of B. fragilis, produces an enterotoxin (BFT; B. fragilis toxin), leading to asymptomatic chronic infections and colonic tumor formation. However, the impact of B. fragilis and ETBF on the clinical outcome of colorectal cancer (CRC) remains unclear. We aim to assess whether their presence affects the outcome in patients with CRC after curative resection. METHODS: We obtained 197 pairs of matched formalin-fixed paraffin-embedded samples from cancerous and adjacent non-cancerous tissues of patients with pathological stage (pstage) II and III CRC after curative resection. The presence of B. fragilis and ETBF were estimated using real-time polymerase chain reaction, and recurrence-free survival (RFS) and overall survival (OS) of the patients were analyzed. RESULTS: 16S rRNA for B. fragilis and bft DNA were detected in 120 (60.9%) and 12 (6.1%) of the 197 patients, respectively. B. fragilis-positive patients had better RFS than B. fragilis-negative patients, although that was not statistically significant. In subgroup analysis, better outcomes on RFS were observed in the presence of B. fragilis in pstage II and left-sided CRC. The association of B. fragilis positivity on OS was accentuated in the depth of T4 subgroup. No significant differences were observed in RFS and OS between ETBF and non-toxigenic B. fragilis. CONCLUSIONS: Our findings suggest that the presence of B. fragilis is associated with better outcomes in patients with pstage II and III CRC after curative resection.

World's first report of sigmoidectomy for sigmoid cancer using the Saroa surgical system with tactile feedback.

Increasing evidence based on the safety and benefits of robot-assisted surgery indicates the disadvantage of the lack of tactile feedback. A lack of tactile feedback increases the risk of intraoperative complications, prolongs operative times, and delays the learning curve. A 40-year-old female patient presented to our hospital with a positive fecal occult blood test. A colonoscopy revealed type 2 advanced cancer of the sigmoid colon, and histological examination showed a well-differentiated adenocarcinoma. Furthermore, abdominal contrast-enhanced computed tomography revealed a tumor in the sigmoid colon and several swollen lymph nodes in the colonic mesentery without distant metastases. The patient was diagnosed with cStage IIIb (cT3N1bM0) sigmoid cancer and underwent sigmoidectomy using the Saroa Surgical System, which was developed by RIVERFIELD, a venture company at the Tokyo Medical and Dental University, and the Tokyo Institute of Technology. Based on adequate simulation, surgery was safely performed with appropriate port placement and arm base-angle adjustment. The operating time was 176 min, with a console time of 116 min and 0 ml blood loss. The patient was discharged 6 days postoperatively without complications. The pathological diagnosis was adenocarcinoma, tub1, tub2, pT2N1bM0, and pStage IIIa. Herein, we report the world's first surgery for sigmoid cancer using the Saroa Surgical System with tactile feedback in which a safe and appropriate oncological surgery was performed.

Histological study of the structural layers around the esophagus in the lower mediastinum.

BACKGROUND: In Japan, the transhiatal approach, including lower mediastinal lymph node dissection, is widely performed for Siewert type II esophagogastric junction adenocarcinoma. This procedure is generally performed in a magnified view using laparoscopy or a robotic system, therefore, the microanatomy of the lower mediastinum is important. However, mediastinal microanatomy is still unclear and classification of lower mediastinal lymph nodes is not currently based on fascia or other microanatomical structures. AIM: To clarify the fascia and layer structures of the lower mediastinum and classify the lower mediastinal tissue. METHODS: We dissected the esophagus and surrounding organs en-bloc from seven cadavers fixed in 10% formalin. Organs and tissues were then cut at the level of the lower thoracic esophagus, embedded in paraffin, and serially sectioned. Tissue sections were stained with Hematoxylin-Eosin (all cadavers) and immunostained for the lymphatic endothelial marker D2-40 (three cadavers). We observed the periesophageal fasciae and layers, and defined lymph node boundaries based on the fasciae. Lymphatic vessels around the esophagus were observed on immunostained tissue sections. RESULTS: We identified two fasciae, A and B. We then classified lower mediastinal tissue into three areas, paraesophageal, paraaortic, and intermediate, using these fasciae as boundaries. Lymph nodes were found to be present and were counted in each area. The dorsal part of the intermediate area was thicker on the caudal side than on the cranial side in all cadavers. On the dorsal side, no blood vessels penetrated the fasciae in six of the seven cadavers, whereas the proper esophageal artery penetrated fascia B in one cadaver. D2-40 immunostaining showed lymphatic vessel connections between the paraesophageal and intermediate areas on the lateral and ventral sides of the esophagus, but no lymphatic connection between areas on the dorsal side of the esophagus. CONCLUSION: Histological studies identified two fasciae surrounding the esophagus in the lower mediastinum and the layers separated by these fasciae were used to classify the lower mediastinal tissues.

Identifying Risk Factors of Complications following Total Gastrectomy for Gastric Cancer: Comparison between Splenectomy and Spleen-Preserving Surgery - A Supplementary Analysis of JCOG0110.

INTRODUCTION: Splenectomy for proximal gastric cancer was found to offer no survival benefit in a randomized trial clarifying the role of splenectomy (JCOG0110 study). Although many studies have explored risk factors for morbidities following total gastrectomy, none have assessed the risk factors for postoperative complications in spleen-preserving total gastrectomy. METHODS: Using data from 505 patients enrolled in a previous randomized trial, risk factors for postoperative complications were identified by multivariable logistic regression analysis. Then, the risk factors were assessed separately between splenectomy and spleen-preserving total gastrectomy. RESULTS: Postoperative complications were identified in 119 patients (23.6%) and were more common following splenectomy than following spleen-preserving surgery (30.7% and 16.1%, respectively, p < 0.01). Multivariable analysis revealed that age ≥65 years (p = 0.032), body mass index ≥25 (p = 0.003), and blood loss ≥350 (p = 0.019) were independent risk factors for postoperative complications in the entire cohort. Among them, only body mass index was a significant independent risk factor for complications in both spleen preservation (p = 0.047) and splenectomy groups (p = 0.017). CONCLUSION: Risk factors for postoperative complications were essentially the same between splenectomy and spleen preservation. Being overweight increased the risk of postoperative complications.

Determination of the Minimum Sample Amount for Capillary Electrophoresis-Fourier Transform Mass Spectrometry (CE-FTMS)-Based Metabolomics of Colorectal Cancer Biopsies.

The minimum sample volume for capillary electrophoresis-Fourier transform mass spectrometry (CE-FTMS) useful for analyzing hydrophilic metabolites was investigated using samples obtained from colorectal cancer patients. One, two, five, and ten biopsies were collected from tumor and nontumor parts of the surgically removed specimens from each of the five patients who had undergone colorectal cancer surgery. Metabolomics was performed on the collected samples using CE-FTMS. To determine the minimum number of specimens based on data volume and biological interpretability, we compared the number of annotated metabolites in each sample with different numbers of biopsies and conducted principal component analysis (PCA), hierarchical cluster analysis (HCA), quantitative enrichment analysis (QEA), and random forest analysis (RFA). The number of metabolites detected in one biopsy was significantly lower than those in 2, 5, and 10 biopsies, whereas those detected among 2, 5, and 10 pieces were not significantly different. Moreover, a binary classification model developed by RFA based on 2-biopsy data perfectly distinguished tumor and nontumor samples with 5- and 10-biopsy data. Taken together, two biopsies would be sufficient for CE-FTMS-based metabolomics from a data content and biological interpretability viewpoint, which opens the gate of biopsy metabolomics for practical clinical applications.

Distribution of splenic artery lymph nodes and splenic hilar lymph nodes.

BACKGROUND: Total gastrectomy with splenectomy is the standard treatment for advanced proximal gastric cancer with greater-curvature invasion. As an alternative to splenectomy, laparoscopic spleen-preserving splenic hilar lymph node (LN) dissection (SPSHLD) has been developed. With SPSHLD, the posterior splenic hilar LNs are left behind. AIM: To clarify the distribution of splenic hilar (No. 10) and splenic artery (No. 11p and 11d) LNs and to verify the possibility of omitting posterior LN dissection in laparoscopic SPSHLD from an anatomical standpoint. METHODS: Hematoxylin & eosin-stained specimens were prepared from six cadavers, and the distribution of LN No. 10, 11p, and 11d was evaluated. In addition, heatmaps were constructed and three-dimensional reconstructions were created to visualize the LN distribution for qualitative evaluation. RESULTS: There was little difference in the number of No. 10 LNs between the anterior and posterior sides. For LN No. 11p and 11d, the anterior LNs were more numerous than the posterior LNs in all cases. The number of posterior LNs increased toward the hilar side. Heatmaps and three-dimensional reconstructions showed that LN No. 11p was more abundant in the superficial area, while LN No. 11d and 10 were more abundant in the deep intervascular area. CONCLUSION: The number of posterior LNs increased toward the hilum and was not neglectable. Thus, surgeons should consider that some posterior No. 10 and No. 11d LNs may remain after SPSHLD.

Ginseng mediates its anticancer activity by inhibiting the expression of DNMTs and reactivating methylation-silenced genes in colorectal cancer.

Developing safe and effective therapeutic modalities remains a critical challenge for improving the prognosis of patients with colorectal cancer (CRC). In this regard, targeting epigenetic regulation in cancers has recently emerged as a promising therapeutic approach. Since several natural compounds have recently been shown to be important epigenetic modulators, we hypothesized that Ginseng might exert its anticancer activity by regulating DNA methylation alterations in CRC. In this study, a series of cell culture studies were conducted, followed by their interrogation in patient-derived 3D organoid models to evaluate Ginseng's anticancer activity in CRC. Genome-wide methylation alterations were interrogated by undertaking MethylationEpic BeadChip microarrays. First, 50% inhibitory concentrations (IC50) were determined by cell viability assays, and subsequent Ginseng treatment demonstrated a significant anticancer effect on clonogenicity and cellular migration in CRC cells. Treatment with Ginseng potentiated cellular apoptosis through regulation of apoptosis-related genes in CRC cells. Furthermore, Ginseng treatment downregulated the expression of DNA methyltransferases (DNMTs) and decreased the global DNA methylation levels in CRC cells. The genome-wide methylation profiling identified Ginseng-induced hypomethylation of transcriptionally silenced tumor suppressor genes. Finally, cell culture-based findings were successfully validated in patient-derived 3D organoids. In conclusion, we demonstrate that Ginseng exerts its antitumorigenic potential by regulating cellular apoptosis via the downregulation of DNMTs and reversing the methylation status of transcriptionally silenced genes in CRC.

RTP4 silencing provokes tumor-intrinsic resistance to immune checkpoint blockade in colorectal cancer.

BACKGROUND: Recent advances in immune checkpoint blockade (ICB) have improved patient prognosis in mismatch repair-deficient and microsatellite instability-high colorectal cancer (dMMR/MSI-H CRC); however, PD-1 blockade has faced a challenge in early progressive disease. We aimed to understand the early event in ICB resistance using an in vivo model. METHODS: We subcutaneously transplanted the MC38 colon cancer cells into C57BL/6 mice, intraperitoneally injected anti-PD-1 antibody and then isolated ICB-resistant subclones from the recurrent tumors. RESULTS: Comparative gene expression analysis discovered seven genes significantly downregulated in the ICB-resistant cells. Tumorigenicity assay of the MC38 cells knocked out each of the seven candidate genes into C57BL/6 mice treated with anti-PD-1 antibody and bioinformatics analysis of the relationship between the expression of the seven candidate genes and the outcome of cancer patients receiving immunotherapy identified Rtp4, an interferon-stimulated gene and a chaperon protein of G protein-coupled receptors, as a gene involved in ICB resistance. Immunohistochemical analysis of transplanted tumor tissues demonstrated that anti-PD-1 antibody failed to recruit T lymphocytes in the Rtp4-KO MC38 cells. Mouse and human RTP4 expression could be silenced via histone H3 lysine 9 (H3K9) trimethylation, and public transcriptome data indicated the high expression level of RTP4 in most but not all of dMMR/MSI-H CRC. CONCLUSIONS: We clarified that RTP4 could be silenced by histone H3K9 methylation as the early event of ICB resistance. RTP4 expression could be a promising biomarker for predicting ICB response, and the combination of epigenetic drugs and immune checkpoint inhibitors might exhibit synergistic effects on dMMR/MSI-H CRC.

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.

Optimal placement of self-fixating mesh in the rectus abdominis muscle for ventral hernia repair when using the enhanced-view totally extraperitoneal Rives-Stoppa technique.

INTRODUCTION: Laparoscopic retro-muscular Rives-Stoppa (RS) ventral hernia repair using the enhanced-view totally extraperitoneal (eTEP) technique (eTEP-RS) is becoming common. Although self-fixating mesh is useful with good fixation, some surgeons think the fixating surface must be oriented towards the rectus abdominis muscle for safety reasons in eTEP-RS. Attaching the self-fixating mesh to the rectus abdominis, the ceiling of the operative field, is challenging and time-consuming. MATERIAL AND SURGICAL TECHNIQUE: First, the self-fixating mesh is folded in half with the fixation surface facing outwards. Second, we create a partition sheet and insert the sheet between the two arms of the folded mesh. The folded mesh is then inserted intracorporeally. We can unfold the mesh easily from one-quarter width to half width on the rectus abdominis muscle because of the insertion of the partition sheet. Finally, the mesh is unfolded to full width, and the mesh placement is completed. DISCUSSION: The eTEP-RS is still a new procedure and has not yet been standardized. However, our technique will increase the use of self-fixating mesh and improve the outcomes of eTEP-RS.

A comparison of the short-term outcomes between laparoscopic and robotic distal gastrectomy: A retrospective study using a nationwide inpatient database.

BACKGROUND: Although the safety of robotic distal gastrectomy has been studied in several single-center trials, the nationwide outcomes of robotic distal gastrectomy that meet the requirements of Japanese national health insurance, such as facility case volume and skill level of the surgeon, are still not clear. The objective of this study was to evaluate the short-term outcomes of robotic distal gastrectomy, which was covered by national health insurance, compared to laparoscopic distal gastrectomy. METHODS: We retrieved gastric cancer cases with cStage I to III who underwent laparoscopic distal gastrectomy (15,539 patients) and robotic distal gastrectomy (1,312 patients) between April 2018 and March 2020 from the Diagnosis Procedure Combination database. We compared the frequency of postoperative complications, anesthesia time, and postoperative hospitalization days between laparoscopic distal gastrectomy and robotic distal gastrectomy using propensity score matching analysis. RESULTS: The postoperative complication rate were not different between laparoscopic distal gastrectomy and robotic distal gastrectomy (odds ratio = 0.90, 95% confidence interval: 0.66 to 1.23, P = .52). The anesthesia time (minutes) was significantly longer (coefficient = 70.2, 95% confidence interval: 63.8 to 76.7, P < .001) and postoperative hospitalization (days) was significantly shorter (coefficient = -0.89, 95% confidence interval: -1.48 to -0.31, P = .003) in robotic distal gastrectomy than laparoscopic distal gastrectomy. CONCLUSIONS: Robotic distal gastrectomy that met strict national health insurance coverage requirements in Japan was performed as safely as laparoscopic distal gastrectomy with reduced hospitalization days.