Management challenges and the role of adjuvant chemotherapy in remnant gastric cancer: an analysis of 313 patients from the KEGG multicenter observational study.

BACKGROUND: Clinical findings and postoperative follow-up data on remnant gastric cancer (RGC) are limited due to its rarity. Additionally, the preoperative staging, radical surgery, and managing recurrence in RGC present significant clinical challenges. METHODS: We analyzed the clinicopathological findings, adjuvant chemotherapy, and patterns of postoperative recurrence of 313 consecutive patients who underwent curative surgery for RGC at 17 Japanese institutions. This study investigated the optimal management of RGC and the impact of adjuvant chemotherapy (AC) on recurrence-free survival (RFS). RESULTS: Pathological stages I, II, and III were observed in 55.9% (N = 175), 24.9% (N = 78), and 19.2% (N = 60) of the patients, respectively. The overall concordance rate between clinical and pathological T staging was 58.3%, with a clinical T4 sensitivity of 41.4% for diagnosing pathological T4. During the median follow-up period of 4.6 years, disease recurrence occurred in 24.3% of patients. Most recurrences (over 80%) occurred within 2.5 years, and 96.1% within 5 years after RGC surgery. Peritoneal recurrence was the most common in patients with advanced RGC, accounting for 14.1% in stage II and 28.3% in stage III. Multivariable regression analysis showed that AC was significantly associated with a longer RFS, with a hazard ratio of 0.45 (95% confidence interval: 0.26-0.76). CONCLUSIONS: Our study underscores the importance of early detection, accurate preoperative staging, and postoperative surveillance in managing advanced RGC cases. Despite some limitations, our findings indicate that AC may provide survival benefits comparable to those seen in primary gastric cancer.

Low-grade appendiceal mucinous neoplasm penetrating sigmoid colon: A case report.

Low-grade appendiceal mucinous neoplasm (LAMN) is principally characterized by low-grade cytology without evidence of invasion to other organs. We report a LAMN surgical case whose appendiceal tumor penetrated the sigmoid colon wall. An 87-year-old man was referred for endoscopic resection (ER) of a colon polyp. Despite four ERs over 5 years, the polyp recurred at the same site. Laparoscopic surgery revealed a dilated appendix firmly attached to the sigmoid colon. We performed en bloc resection of both the sigmoid colon and appendix without tumor exposure. The histopathological evaluation showed that the LAMN had penetrated the sigmoid colon wall, forming two polyps on the colonic mucosa. In cases where the appendiceal-colonic fistula is suspected, en bloc resection of the appendix and colon wall should be considered.

Laparoscopic vs. open surgery for rectal cancer in patients with obesity: short-term outcomes and relapse-free survival across age groups.

PURPOSE: To investigate the efficacy of laparoscopic surgery for rectal cancer in obese and older patients, who are often characterized by a higher prevalence of comorbidities and physical decline. METHODS: This large-scale multicenter retrospective cohort study included 524 patients with a body mass index of 25 or higher who underwent either open or laparoscopic surgery for stage II or III rectal cancer between 2009 and 2013. We assessed the short-term outcomes and relapse-free survival by comparing these surgical modalities. The patients were stratified into 404 non-elderly (< 70 years) and 120 elderly (≥ 70 years) patients. RESULTS: In both patient groups, laparoscopic surgery was associated with a significantly reduced blood loss (non-elderly: 41 vs. 545 ml; elderly: 50 vs. 445 ml) and shorter hospital stays (non-elderly: 10 vs. 19 days; elderly: 15 vs. 20 days) than open surgery. The overall complications and relapse-free survival showed no significant differences between the two surgical techniques in either age group. Additionally, the impact of the laparoscopic procedure on the relapse-free survival remained consistent between the age groups. CONCLUSION: Laparoscopic surgery offers short-term benefits for patients with obesity and rectal cancer compared to open surgery, regardless of age, without influencing the long-term prognosis.

Feasibility of Narrow-Spectrum Antimicrobial Agents for Post-Operative Intra-Abdominal Infections After Gastrectomy.

Introduction: Recently, antimicrobial resistance has received considerable attention. Broad-spectrum antimicrobial agents are recommended as the initial therapy for post-operative intra-abdominal infections. However, at our institution, we have adopted a tactic of initially treating post-operative intra-abdominal complications with relatively narrow-spectrum antimicrobial agents, such as second-generation cephalosporins. In the present study, we aimed to retrospectively analyze the use of antimicrobial agents and the resulting treatment outcomes in patients with intra-abdominal complications after gastrectomy at our facility. Methods: We conducted a retrospective observational study of patients treated with antibiotic agents for intra-abdominal infectious complications after gastrectomy between 2011 and 2021. We determined the proportion of "initial treatment failures" associated with the initial administration of antibiotic agents for post-operative intra-abdominal complications. Results: Post-operative intra-abdominal infections were observed in 29 patients. Broad-spectrum antimicrobial agents were not administered. We successfully treated 19 patients. Initial treatment failure was observed in 10 patients, of whom five experienced failure due to bacterial resistance to the initial antimicrobial agent. All 10 patients who experienced initial treatment failure were discharged after drainage procedures or other treatments. There were no deaths due to post-operative complications. Cefmetazole was used as the initial antimicrobial agent in 27 of the 29 patients. Conclusions: Considering that all patients with post-gastrectomy intra-abdominal infections were successfully treated using relatively narrow-spectrum antimicrobial agents, and initial treatment failure due to antimicrobial-resistant pathogens was 17.2%, the use of narrow-range antimicrobial agents for intra-abdominal infections after gastrectomy can be deemed appropriate.

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.

Current insights on social media as a tool for the dissemination of research and education in surgery: a narrative review.

The purpose of our narrative review is to summarize the utilization of social media (SoMe) platforms for research communication within the field of surgery. We searched the PubMed database for articles in the last decade that discuss the utilization of SoMe in surgery and then categorized the diverse purposes of SoMe. SoMe proved to be a powerful tool for disseminating articles. Employing strategic methods like visual abstracts enhances article citation rates, the impact factor, h-index, and Altmetric score (an emerging alternative metric that comprehensively and instantly quantifies the social impact of scientific papers). SoMe also proved valuable for surgical education, with online videos shared widely for surgical training. However, it is essential to acknowledge the associated risk of inconsistency in quality. Moreover, SoMe facilitates discussion on specific topics through hashtags or closed groups and is instrumental in recruiting surgeons, with over half of general surgery residency programs in the US efficiently leveraging these platforms to attract the attention of potential candidates. Thus, there is a wealth of evidence supporting the effective use of SoMe for surgeons. In the contemporary era where SoMe is widely utilized, surgeons should be well-versed in this evidence.

Laparoscopic redo surgery for sigmoid volvulus following laparoscopic sigmoidectomy.

BACKGROUND: Sigmoid volvulus (SV) is an acute abdominal condition characterized by torsion of the sigmoid colon around the mesentery, and often results in intestinal obstruction that may progress to bowel ischemia, necrosis, or perforation. Although SV commonly occurs due to predisposing factors like anatomic variations, age-related motility disorders, chronic constipation, and neurologic diseases, its incidence following sigmoid colon cancer surgery has rarely been reported. Herein, we report a rare case of recurrent SV following laparoscopic sigmoidectomy, which was successfully treated by laparoscopic redo surgery. CASE PRESENTATION: The patient was a 77-year-old man who had previously undergone laparoscopic sigmoidectomy for sigmoid colon cancer. Sixteen months postoperatively, he developed an incisional hernia at the umbilical site, which was treated with a laparoscopic repair using an intraperitoneal onlay mesh. After the hernia surgery, the patient had no anastomotic leakage or stenosis on regular follow-ups. However, 65 months after the first surgery, he presented with abdominal pain and distension. A computed tomography revealed that the remnant sigmoid colon was distended in a twisting manner around the anastomosis, leading to the diagnosis of SV. Although endoscopic de-torsion was successful, the SV recurred 2 months later, requiring elective laparoscopic redo surgery. The procedure involved resection of the sigmoid colon including the prior anastomosis with a left pararectal incision and DST re-anastomosis using a 25-mm circular stapler. The operation lasted 165 min with minimal bleeding and no complications. The postoperative course was uneventful. Pathological analysis confirmed fibrosis without malignancy. The patient remains well without recurrence of SV and anastomotic stenosis more than 5 years after surgery. CONCLUSION: SV following sigmoid colon cancer surgery has rarely been reported. This case illustrates the potential need for prophylaxis against postoperative SV, especially in patients with long sigmoid colon undergoing laparoscopic surgery for colorectal cancer. Further, laparoscopic redo surgery following initial laparoscopic surgery for colorectal cancer can be performed with minimal invasiveness, especially if patient selection is properly managed.

Appendiceal neoplasms derived from appendiceal tip remnants following appendectomy: a report of two cases.

BACKGROUND: Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal "stump". Here, we present two surgical cases of appendiceal neoplasms derived from appendiceal "tip" remnants. CASE PRESENTATION: The first patient was a 71-year-old man who had undergone laparoscopic appendectomy for acute appendicitis 12 years prior. During appendectomy, the appendiceal root was ligated, but the appendix was not completely removed due to severe inflammation. At the most recent presentation, computed tomography (CT) was performed to examine choledocholithiasis, which incidentally revealed a cystic lesion of approximately 90 mm adjacent to the cecum. A retrospective review revealed that the cystic lesion had increased in size over time, and laparoscopic ileocecal resection was performed. Pathology revealed no continuity from the appendiceal orifice to the cyst, and a diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) was made from the appendiceal tip remnant. The patient was discharged without complications. The second patient was a 65-year-old man who had undergone surgery for peritonitis due to severe appendicitis 21 years prior. During this operation, the appendix could not be clearly identified due to severe inflammation; consequently, cecal resection was performed. He was referred to our department with a chief complaint of general fatigue and loss of appetite and a cystic lesion of approximately 85 mm close to the cecum that had increased over time. CT showed irregular wall thickening, and malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological diagnosis revealed mucinous adenocarcinoma (TXN0M0) arising from the remnant appendiceal tip. The patient is undergoing follow-up without postoperative adjuvant chemotherapy, with no evidence of pseudomyxoma peritonei or cancer recurrence for 32 months postoperatively. CONCLUSIONS: If appendicitis-associated inflammation is sufficiently severe that accurate identification of the appendix is difficult, it may remain on the apical side of the appendix, even if the root of the appendix is ligated and removed. If the appendectomy is terminated incompletely, it is necessary to check for the presence of a residual appendix postoperatively and provide appropriate follow-up.

Midesophageal diverticulum with elevated intrabolus pressure: a case report.

BACKGROUND: Esophageal diverticulum is commonly associated with esophageal motility disorders, which can be diagnosed using high-resolution manometry (HRM) according to the Chicago classification. Although midesophageal diverticulum (M-ED) is associated with inflammatory processes, esophageal motility disorders have been recently identified as an etiology of M-ED. CASE PRESENTATION: We present the case of a patient with M-ED and elevated intrabolus pressure (IBP), which did not meet the criteria for esophageal motility disorders according to the Chicago classification. A 71-year-old man presented with gradually worsening dysphagia for two years and was diagnosed as having an 8-cm-long M-ED and multiple small diverticula in lower esophagus. HRM revealed a median integrated relaxation pressure of 14.6 mmHg, a distal latency of 6.4 s, and an average maximum IBP of 35.7 mmHg. He underwent thoracoscopic resection of the M-ED and myotomy, which successfully alleviated the symptoms and reduced the intrabolus pressure to normal levels. CONCLUSIONS: It is important to recognize the esophageal diverticulum pathology with HRM findings even in cases where the results may not meet the Chicago classification and to include myotomy based on the results.

Real-time detection of active bleeding in laparoscopic colectomy using artificial intelligence.

BACKGROUND: Most intraoperative adverse events (iAEs) result from surgeons' errors, and bleeding is the majority of iAEs. Recognizing active bleeding timely is important to ensure safe surgery, and artificial intelligence (AI) has great potential for detecting active bleeding and providing real-time surgical support. This study aimed to develop a real-time AI model to detect active intraoperative bleeding. METHODS: We extracted 27 surgical videos from a nationwide multi-institutional surgical video database in Japan and divided them at the patient level into three sets: training (n = 21), validation (n = 3), and testing (n = 3). We subsequently extracted the bleeding scenes and labeled distinctively active bleeding and blood pooling frame by frame. We used pre-trained YOLOv7_6w and developed a model to learn both active bleeding and blood pooling. The Average Precision at an Intersection over Union threshold of 0.5 (AP.50) for active bleeding and frames per second (FPS) were quantified. In addition, we conducted two 5-point Likert scales (5 = Excellent, 4 = Good, 3 = Fair, 2 = Poor, and 1 = Fail) questionnaires about sensitivity (the sensitivity score) and number of overdetection areas (the overdetection score) to investigate the surgeons' assessment. RESULTS: We annotated 34,117 images of 254 bleeding events. The AP.50 for active bleeding in the developed model was 0.574 and the FPS was 48.5. Twenty surgeons answered two questionnaires, indicating a sensitivity score of 4.92 and an overdetection score of 4.62 for the model. CONCLUSIONS: We developed an AI model to detect active bleeding, achieving real-time processing speed. Our AI model can be used to provide real-time surgical support.

Synergistic antitumor activity by dual blockade of CCR1 and CXCR2 expressed on myeloid cells within the tumor microenvironment.

BACKGROUND: Chemokine signaling within the tumor microenvironment can promote tumor progression. Although CCR1 and CXCR2 on myeloid cells could be involved in tumor progression, it remains elusive what effect would be observed if both of those are blocked. METHODS: We employed two syngeneic colorectal cancer mouse models: a transplanted tumor model and a liver metastasis model. We generated double-knockout mice for CCR1 and CXCR2, and performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type, Ccr1-/-, Cxcr2-/- or Ccr1-/-Cxcr2-/- mice. RESULTS: Myeloid cells that express MMP2, MMP9 and VEGF were accumulated around both types of tumors through CCR1- and CXCR2-mediated pathways. Mice reconstituted with Ccr1-/-Cxcr2-/- BM exhibited the strongest suppression of tumor growth and liver metastasis compared with other three groups. Depletion of CCR1+CXCR2+ myeloid cells led to a higher frequency of CD8+ T cells, whereas the numbers of Ly6G+ neutrophils, FOXP3+ Treg cells and CD31+ endothelial cells were significantly decreased. Furthermore, treatment with a neutralizing anti-CCR1 mAb to mice reconstituted with Cxcr2-/- BM significantly suppressed tumor growth and liver metastasis. CONCLUSION: Dual blockade of CCR1 and CXCR2 pathways in myeloid cells could be an effective therapy against colorectal cancer.

A case of laparoscopic lymphadenectomy for adenocarcinoma of unknown primary incidentally detected as a solitary enlarged lymph node along the common hepatic artery.

BACKGROUND: Even in cancer of unknown primary (CUP), which is rare clinical condition, solitary anterosuperior lymph node (LN) along the common hepatic artery (No.8a LN) enlargement diagnosed as metastatic adenocarcinoma has never been reported. CASE PRESENTATION: A 68-year-old Japanese male, with a history of early gastric cancer that had been completely treated by endoscopic submucosal dissection 26 years ago, was detected a single enlarged nodule along the common hepatic artery, No.8a LN, incidentally by computed tomography performed for monitoring of interstitial pneumonia. Endoscopic ultra-sound-guided fine needle aspiration revealed that this nodule was adenocarcinoma suggestive of metastasis, but other imaging studies, including upper and lower gastrointestinal endoscopy, positron emission tomography, and ultrasonography did not detect any primary cancer. We have finally diagnosed as the LN metastasis of CUP and performed laparoscopic lymphadenectomy for this tumor. The tumor was approximately 5 cm in size, was in close proximity to the pancreas, and involved part of the right gastric artery and vein. LNs in the No.5 and No.8a areas, including this tumor, were dissected laparoscopically, and radical resection was achieved. The patient had no postoperative complication and was discharged on postoperative day 10. Immunohistopathological findings revealed that the tumor was poorly differentiated adenocarcinoma, and different from the histology of gastric cancer resected 26 years ago, although the tumor was suggestive of gastrointestinal origin. Imaging studies performed 2 and 6 months after discharge also did not reveal a primary site. CONCLUSION: We reported a case of solitary No.8a LN adenocarcinoma of CUP. For diagnostic and therapeutic purposes, radical resection is recommended for single enlarged intra-abdominal LN of CUP.

Utility of articulating instruments as an alternative to robotic devices in laparoscopic right hemicolectomy.

Laparoscopic complete mesocolic excision with central vessel ligation has been widely accepted for its oncological benefits in colon cancer surgery. However, laparoscopic right hemicolectomy involves a risk for vascular injury during dissection around the surgical trunk. This technical difficulty has been attributed to the limited movement of conventional laparoscopic forceps. Although robotic devices can overcome the restricted motion of laparoscopic devices, they are not yet widely used. The ArtiSential is an articulating laparoscopic instrument that has a two-joint end-effector that enables a wide range of motion precisely reflecting the surgeon's finger movements, and is designed to compensate for the drawbacks of conventional laparoscopic tools. The present study demonstrated the utility of articulating instruments in laparoscopic right hemicolectomy by comparing the authors' laparoscopic procedures, using articulating instruments, with robotic procedures. Articulating laparoscopic instruments can be successfully maneuvered in virtually the same manner as robotic devices and, as such, represent a viable alternative to robotic surgery. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00654-w.

Anterior versus posterior mediastinal reconstruction after esophagectomy in esophageal cancer patients: a systematic review and meta-analysis.

PURPOSE: Esophagectomy is the primary surgical treatment for esophageal cancer, although other treatment approaches are often incorporated, including preoperative chemotherapy and chemoradiotherapy. The two major routes of esophageal reconstruction after esophagectomy are the anterior mediastinal (retrosternal, heterotopic) and posterior mediastinal (prevertebral, orthotopic) routes. However, which of these two routes of reconstruction is the most appropriate remains controversial. This systematic review aimed to compare the efficacy and safety of anterior mediastinal reconstruction with those of posterior mediastinal reconstruction after esophagectomy in esophageal cancer. METHODS: In January 2022, a literature search of the CENTRAL, MEDLINE, and EMBASE databases was conducted to identify all published and unpublished randomized controlled trials, regardless of language. Eight studies were included for quantitative synthesis. RESULTS: Postoperative death (9/129 and 4/125, risk ratio [RR]: 2.07, 95% confidence interval [CI]: 0.65-6.64) and incidence of anastomotic leak (24/208 and 26/208, RR: 0.95, 95% CI: 0.56-1.62) were not significantly different between the two mediastinal reconstructions. We could not perform a meta-analysis for quality of life, loss of body weight, or postoperative hospital stay due to data limitations. CONCLUSION: Overall, there was low-quality evidence to suggest that the outcomes of the anterior and posterior mediastinal routes of reconstruction are not significantly different in patients with esophageal cancer.

Prediction for oxaliplatin-induced liver injury using patient-derived liver organoids.

BACKGROUND: Liver injury associated with oxaliplatin (L-OHP)-based chemotherapy can significantly impact the treatment outcomes of patients with colorectal cancer liver metastases, especially when combined with surgery. To date, no definitive biomarker that can predict the risk of liver injury has been identified. This study aimed to investigate whether organoids can be used as tools to predict the risk of liver injury. METHODS: We examined the relationship between the clinical signs of L-OHP-induced liver injury and the responses of patient-derived liver organoids in vitro. Organoids were established from noncancerous liver tissues obtained from 10 patients who underwent L-OHP-based chemotherapy and hepatectomy for colorectal cancer. RESULTS: Organoids cultured in a galactose differentiation medium, which can activate the mitochondria of organoids, showed sensitivity to L-OHP cytotoxicity, which was significantly related to clinical liver toxicity induced by L-OHP treatment. Organoids from patients who presented with a high-grade liver injury to the L-OHP regimen showed an obvious increase in mitochondrial superoxide levels and a significant decrease in mitochondrial membrane potential with L-OHP exposure. L-OHP-induced mitochondrial oxidative stress was not observed in the organoids from patients with low-grade liver injury. CONCLUSIONS: These results suggested that L-OHP-induced liver injury may be caused by mitochondrial oxidative damage. Furthermore, patient-derived liver organoids may be used to assess susceptibility to L-OHP-induced liver injury in individual patients.

Paneth-like cells produced from OLFM4+ stem cells support OLFM4+ stem cell growth in advanced colorectal cancer.

Tumor tissues consist of heterogeneous cells that originate from stem cells; however, their cell fate determination program remains incompletely understood. Using patient-derived organoids established from patients with advanced colorectal cancer (CRC), we evaluated the potential of olfactomedin 4 (OLFM4)+ stem cells to produce a bifurcated lineage of progenies with absorptive and secretory properties. In the early phases of organoid reconstruction, OLFM4+ cells preferentially gave rise to secretory cells. Additionally, we found that Paneth-like cells, which do not exist in the normal colon, were induced in response to Notch signaling inhibition. Video recordings of single OLFM4+ cells revealed that organoids containing Paneth-like cells were effectively propagated and that their selective ablation led to organoid collapse. In tumor tissues, Paneth-like cells were identified only in the region where tumor cells lost cell adhesion. These findings indicate that Paneth-like cells are directly produced by OLFM4+ stem cells and that their interaction contributes to tumor formation by providing niche factors. This study reveals the importance of the cell fate specification program for building a complete tumor cellular ecosystem, which might be targeted with novel therapeutics.

Downregulation of osteoprotegerin in colorectal cancer cells promotes liver metastasis via activating tumor-associated macrophage.

Osteoprotegerin (OPG) is a secreted cytokine that functions as a decoy receptor for receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL). Anti-RANKL treatment for bone metastasis has been widely accepted for solid tumors. However, the mechanism of OPG-RANKL-RANK signaling in systemic colorectal cancer (CRC) metastasis remains unclear. In this study, we investigated the relevance and function of OPG expression in CRC liver metastasis. First, we performed in silico analysis using The Cancer Genome Atlas public database and found that lower OPG expression in CRC was associated with poor overall survival. Immunohistochemistry analyses using resected specimen from patients with CRC in our institute confirmed the result. Patient-matched primary CRC and liver metastases showed a significant downregulation of OPG expression in metastatic lesions. In CRC cell lines, OPG expression did not suppress cell proliferation and migration. However, OPG expression inhibited macrophage migration by suppressing the RANKL-RANK pathway. Moreover, in vivo mouse liver metastasis models showed that OPG expression in CRC cells suppressed liver metastases. In addition, treatment with an anti-RANKL neutralizing antibody also suppressed liver metastases. These results showed that downregulation of OPG expression in CRC cells promotes liver metastasis by activating tumor-associated macrophage, which can become a candidate for targeted therapy with anti-RANKL neutralizing antibody for CRC liver metastasis.

Lineage tracing of T cell differentiation from T-iPSC by 2D feeder-free culture and 3D organoid culture.

Introduction: T cells induced from induced pluripotent stem cells(iPSCs) derived from antigen-specific T cells (T-iPS-T cells) are an attractive tool for T cell immunotherapy. The induction of cytotoxic T-iPS-T cells is well established in feeder-free condition for the aim of off-the-shelf production, however, the induction of helper T-iPS-T cells remains challenging. Methods: We analyzed T-iPS-T cells matured in 3D organoid culture at different steps in the culture process at the single-cell level. T-iPS-T cell datasets were merged with an available human thymocyte dataset based in single-cell RNA sequencing (scRNA-seq). Particularly, we searched for genes crucial for generation CD4+ T-iPS-T cells by comparing T-iPS-T cells established in 2D feeder-free or 3D organoid culture. Results: The scRNA-seq data indicated that T-iPS-T cells are similar to T cells transitioning to human thymocytes, with SELENOW, GIMAP4, 7, SATB1, SALMF1, IL7R, SYTL2, S100A11, STAT1, IFITM1, LZTFL1 and SOX4 identified as candidate genes for the 2D feeder-free induction of CD4+ T-iPS-T cells. Discussion: This study provides single cell transcriptome datasets of iPS-T cells and leads to further analysis for CD4+ T cell generation from T-iPSCs.