Safety and feasibility of minimally invasive gastrectomy following preoperative chemotherapy for highly advanced gastric cancer.

BACKGROUND: This study aimed to determine the safety and feasibility of minimally invasive gastrectomy in patients who underwent preoperative chemotherapy for highly advanced gastric cancer. METHODS: Preoperative chemotherapy was indicated for patients with advanced large tumors (≥ cT3 and ≥ 5 cm) and/or bulky node metastasis (≥ 3 cm × 1 or ≥ 1.5 cm × 2). Between January 2009 and March 2022, 150 patients underwent preoperative chemotherapy followed by gastrectomy with R0 resection, including conversion surgery (robotic, 62; laparoscopic, 88). The outcomes of these patients were retrospectively examined. RESULTS: Among them, 41 and 47 patients had stage IV disease and underwent splenectomy, respectively. Regarding operative outcomes, operative time was 475 min, blood loss was 72 g, morbidity (grade ≥ 3a) rate was 12%, local complication rate was 10.7%, and postoperative hospital stay was 14 days (Interquartile range: 11-18 days). Fifty patients (33.3%) achieved grade ≥ 2 histological responses. Regarding resection types, total/proximal gastrectomy plus splenectomy (29.8%) was associated with significantly higher morbidity than other types (distal gastrectomy, 3.2%; total/proximal gastrectomy, 4.9%; P < 0.001). Specifically, among splenectomy cases, the rate of postoperative complications associated with the laparoscopic approach was significantly higher than that associated with the robotic approach (40.0% vs. 0%, P = 0.009). In the multivariate analysis, splenectomy was an independent risk factor for postoperative complications [odds ratio, 8.574; 95% confidence interval (CI), 2.584-28.443; P < 0.001]. CONCLUSIONS: Minimally invasive gastrectomy following preoperative chemotherapy was feasible and safe for patients with highly advanced gastric cancer. Robotic gastrectomy may improve surgical safety, particularly in the case of total/proximal gastrectomy combined with splenectomy.

Risk factors for residual liver recurrence of colorectal cancer after resection of liver metastases and significance of adjuvant chemotherapy.

OBJECTIVE: The risk factors for residual liver recurrence after resection of colorectal cancer liver metastases were analyzed separately for synchronous and metachronous metastases. METHODS: This retrospective study included 236 patients (139 with synchronous and 97 with metachronous lesions) who underwent initial surgery for colorectal cancer liver metastases from April 2010 to December 2021 at the Fujita Health University Hospital. We performed univariate and multivariate analyses of risk factors for recurrence based on clinical background. RESULTS: Univariate analysis of synchronous liver metastases identified three risk factors: positive lymph nodes (p = 0.018, HR = 2.067), ≥3 liver metastases (p < 0.001, HR = 2.382), and use of adjuvant chemotherapy (p = 0.013, HR = 0.560). Multivariate analysis identified the same three factors. For metachronous liver metastases, univariate and multivariate analysis identified ≥3 liver metastases as a risk factor (p = 0.002, HR = 2.988); however, use of adjuvant chemotherapy after hepatic resection was not associated with a lower risk of recurrence for metachronous lesions. Inverse probability of treatment weighting analysis of patients with these lesions with or without adjuvant chemotherapy after primary resection showed that patients with metachronous liver metastases who did not receive this treatment had fewer recurrences when adjuvant therapy was administered after subsequent liver resection, although the difference was not significant. Patients who received adjuvant chemotherapy after hepatic resection had less recurrence but less benefit from this treatment. CONCLUSION: Risk factors for liver recurrence after resection of synchronous liver metastases were positive lymph nodes, ≥3 liver metastases, and no postoperative adjuvant chemotherapy. Adjuvant chemotherapy is recommended after hepatic resection of synchronous liver metastases.

Utility of the refined EBMT diagnostic and severity criteria 2023 for sinusoidal obstruction syndrome/veno-occlusive disease.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis of SOS/VOD is associated with improved clinical outcomes. In 2023, the refined European Society for Blood and Marrow Transplantation diagnostic and severity criteria (refined EBMT criteria 2023) have been advocated. The revision has introduced new diagnostic categories, namely; probable, clinical, and proven SOS/VOD. In addition, the Sequential Organ Failure Assessment (SOFA) score has been newly incorporated into the SOS/VOD severity grading. We performed a retrospective analysis to evaluate the utility of these criteria. We analyzed 161 cases who underwent allogeneic HSCT. We identified 53 probable, 23 clinical, and 4 proven SOS/VOD cases. Probable SOS/VOD was diagnosed a median of 5.0 days earlier (interquartile range: 2-13 days, P < 0.001) than that of clinical SOS/VOD. The development of probable SOS/VOD alone was associated with a significantly inferior survival proportion compared to non-SOS/VOD (100-day survival, 86.2% vs. 94.3%, P = 0.012). The SOFA score contributed to the prediction of prognosis. Consequently, the refined EBMT criteria 2023 demonstrated the utility of SOS/VOD diagnosis and severity grading. Further investigations and improvements in these criteria are warranted.

Asciminib in Patients With CML-CP Previously Treated With ≥ 2 Tyrosine Kinase Inhibitors: 96-Week Results From the Japanese Subgroup Analysis of the ASCEMBL Study.

Asciminib is a first-in-class BCR::ABL1 inhibitor that Specifically Targets the ABL1 Myristoyl Pocket (STAMP). It is approved worldwide and in Japan for chronic myeloid leukemia in chronic phase (CML-CP) with resistance or intolerance to previous tyrosine kinase inhibitor (TKI) therapy. In the Phase 3 ASCEMBL study, patients with CML-CP who received ≥ 2 prior ATP-competitive TKIs were randomized (2:1) to asciminib 40 mg twice-daily or bosutinib 500 mg once-daily. Here, we report the 96-week results of the subgroup analysis of Japanese patients (asciminib, n = 13; bosutinib, n = 3) in the ASCEMBL study. The MMR rate at Week 96 was 46.2% in asciminib-treated patients, increasing from Weeks 24 and 48. Patients who achieved MMR at Week 24 remained in MMR up to the Week 96 cutoff. While a high proportion of patients treated with asciminib remained on treatment at cutoff, none randomized to bosutinib were on treatment at Week 96. Despite the longer duration of exposure to asciminib, its safety and tolerability continued to be favorable with no new or worsening safety findings. Overall, the efficacy and safety outcomes in the Japanese subgroup were comparable with the ASCEMBL global study population, which supports the use of asciminib in Japanese patients with previously treated CML-CP.

Preclinical evaluation of the efficacy of an antibody to human SIRPα for cancer immunotherapy in humanized mouse models.

Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment and are considered potential targets for cancer immunotherapy. To examine the antitumor effects of agents targeting human TAMs in vivo, we here established preclinical tumor xenograft models based on immunodeficient mice that express multiple human cytokines and have been reconstituted with a human immune system by transplantation of human CD34+ hematopoietic stem and progenitor cells (HIS-MITRG mice). HIS-MITRG mice supported the growth of both human cell line (Raji)- and patient-derived B cell lymphoma as well as the infiltration of human macrophages into their tumors. We examined the potential antitumor action of an antibody to human SIRPα (SE12C3) that inhibits the interaction of CD47 on tumor cells with SIRPα on human macrophages and thereby promotes Fcγ receptor-mediated phagocytosis of the former cells by the latter. Treatment with the combination of rituximab (antibody to human CD20) and SE12C3 inhibited Raji tumor growth in HIS-MITRG mice to a markedly greater extent than did rituximab monotherapy. This enhanced antitumor effect was dependent on human macrophages and attributable to enhanced rituximab-dependent phagocytosis of lymphoma cells by human macrophages. Treatment with rituximab and SE12C3 also induced reprogramming of human TAMs toward a proinflammatory phenotype. Furthermore, the combination treatment essentially prevented the growth of patient-derived diffuse large B cell lymphoma in HIS-MITRG mice. Our findings thus support the study of HIS-MITRG mice as a model for the preclinical evaluation in vivo of potential therapeutics, such as antibodies to human SIRPα, that target human TAMs.