Feasibility of Multilevel Anterior Lumbar Interbody Fusion in a Patient With an Intrapelvic Kidney: A Case Report.

CASE: We present a 64-year-old woman with loss of lumbar lordosis with a preoperative computed tomography scan demonstrating the presence of an intrapelvic kidney with aberrant vasculature. A 2-level anterior lumbar interbody fusion with a 2-level oblique interbody fusion was planned. An anterior approach was successfully used to access the anterior spine without damaging the pelvic kidney. CONCLUSION: Anatomic variations, both congenital and acquired, can pose significant challenges to surgeons during their dissection. We present a case where multilevel anterior interbody cage placement can be safely performed, even in a patient whose anatomy is complicated by an intrapelvic kidney.

Prediction of programmed death-1 expression status in non-small cell lung cancer based on intratumoural and peritumoral computed tomography (CT) radiomics nomogram.

AIMS: This study aimed to predict the expression of programmed death-1 (PD-1) in non-small cell lung cancer (NSCLC) using intratumoral and peritumoral computed tomography (CT) radiomics nomogram. MATERIALS AND METHODS: Two hundred patients pathologically diagnosed with NSCLC from two hospitals were retrospectively analyzed. Of these, 159 NSCLC patients from our hospital were randomly divided into a training cohort (n=96) and an internal validation cohort (n=63) at a ratio of 6:4, while 41 NSCLC patients from another medical institution served as the external validation cohort. The radiomic features of the gross tumor volume (GTV) and peritumoral volume (PTV) were extracted from the CT images. Optimal radiomics features were selected using least absolute shrinkage and selection operator regression analysis. Finally, a CT radiomics nomogram of clinically independent predictors combined with the best rad-score was constructed. RESULTS: Compared with the 'GTV' and 'PTV' radiomics models, the combined 'GTV + PTV' radiomics model showed better predictive performance, and its area under the curve (AUC) values in the training, internal validation, and external validation cohorts were 0.90 (95% confidence interval [CI]: 0.83-0.97), 0.85 (95% CI: 0.74-0.96) and 0.78 (95% CI: 0.63-0.92). The nomogram constructed by the rad-score of the 'GTV + PTV' radiomics model combined with clinical independent predictors (prealbumin and monocyte) had the best performance, with AUC values in each cohort being 0.92 (95% CI: 0.85-0.98), 0.88 (95% CI: 0.78-0.97), and 0.80 (95% CI: 0.66-0.94), respectively. CONCLUSION: The intratumoral and peritumoral CT radiomics nomogram may facilitate individualized prediction of PD-1 expression status in patients with NSCLC.

SWI/SNF family mutations in advanced NSCLC: genetic characteristics and immune checkpoint inhibitors' therapeutic implication.

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.

A multicenter randomized controlled trial comparing short- and medium-term outcomes of novel biologics and lightweight synthetic mesh for laparoscopic inguinal hernia repair.

INTRODUCTION: The use of biological graft in laparoscopic inguinal hernia repair (LIHR) has been controversial, and there is a lack of high-level evidence to confirm the value of biological graft in LIHR. The purpose of this study is to evaluate the effectiveness of a novel composite biologics in LIHR. METHODS: A multicenter, single-blinded, randomized controlled clinical trial was designed. Fifty patients with unilateral primary inguinal hernia were randomly assigned to the experimental and control group (1:1). The experimental group was repaired with a non-crosslinked composite extracellular matrix from porcine urinary bladder matrix and small intestinal submucosa (UBM/SIS). The control group was repaired with a lightweight, large-pore, synthetic mesh. The primary endpoint was the effectiveness rate of hernia repair. RESULTS: The patients were followed up for four years. No significant difference was found between the experimental group and the control group in the effective rate of hernia repair (24/24[100%] vs 21/22[95.45%], RR, 0.4667; 95%CI, 0.3294-2.304; P = 0.4783). There was no fever, seroma, infection, groin pain, foreign body discomfort or recurrence in the experimental group during the follow-up. In the control group, there were 2 cases of seroma 14 days after operation, 1 case of groin discomfort 60 days after operation and one case of recurrence 410 days after surgery. CONCLUSION: Compared with the lightweight synthetic mesh, the novel UBM/SIS graft has comparable short-term and medium-term effectiveness in LIHR, and the incidence of postoperative complications such as seroma groin discomfort is lower. Trial registration Clinical Trials Registry: ChiCTR1800020173.

Genetic diversity and selection signatures in Hainan black goats revealed by whole-genome sequencing data.

Understanding the genetic characteristics of indigenous goat breeds is crucial for their conservation and breeding efforts. Hainan black goats, as a native breed of south China's tropical island province of Hainan, possess distinctive traits such as black hair, a moderate growth rate, good meat quality, and small body size. However, they exhibit exceptional resilience to rough feeding conditions, possess high-quality meat, and show remarkable resistance to stress and heat. In this study, we resequenced the whole genome of Hainan black goats to study the economic traits and genetic basis of these goats, we leveraged whole-genome sequencing data from 33 Hainan black goats to analyze single nucleotide polymorphism (SNP) density, Runs of homozygosity (ROH), Integrated Haplotype Score (iHS), effective population size (Ne), Nucleotide diversity Analysis (Pi) and selection characteristics. Our findings revealed that Hainan black goats harbor a substantial degree of genetic variation, with a total of 23 608 983 SNPs identified. Analysis of ROHs identified 53 710 segments, predominantly composed of short fragments, with inbreeding events mainly occurring in ancient ancestors, the estimates of inbreeding based on ROH in Hainan black goats typically exhibit moderate values ranging from 0.107 to 0.186. This is primarily attributed to significant declines in the effective population size over recent generations. Moreover, we identified 921 candidate genes within the intersection candidate region of ROH and iHS. Several of these genes are associated with crucial traits such as immunity (PTPRC, HYAL1, HYAL2, HYAL3, CENPE and PKN1), heat tolerance (GNG2, MAPK8, CAPN2, SLC1A1 and LEPR), meat quality (ACOX1, SSTR1, CAMK2B, PPP2CA and PGM1), cashmere production (AKT4, CHRM2, OXTR, AKT3, HMCN1 and CDK19), and stress resistance (TLR2, IFI44, ENPP1, STK3 and NFATC1). The presence of these genes may be attributed to the genetic adaptation of Hainan black goats to local climate conditions. The insights gained from this study provide valuable references and a solid foundation for the preservation, breeding, and utilization of Hainan black goats and their valuable genetic resources.

Nomogram based on MRI and clinical features to predict progression-free survival in patients with stage IIIC1r cervical squamous cell carcinoma: A two-center study.

PURPOSE: To develop a nomogram based on MRI and clinical features to predict progression-free survival (PFS) of 2018 FIGO stage ⅢC1r cervical squamous cell carcinoma (CSCC). METHODS: 144 consecutive patients with stage ⅢC1r CSCC from two independent institutions were stratified into training cohort (from Institution 1, n=100) and independent validation cohort (from Institution 2, n=44). Univariate and multivariate Cox regression analyses of MRI and clinical features before treatment were performed to determine independent risk factors for PFS in training cohort. Nomogram was developed based on them. Concordance index (C-index), calibration curves, and receiver operating characteristic (ROC) analyses were performed to assess and validate the nomogram. RESULTS: In training cohort, 2009 FIGO stage, maximum length of the primary tumor, short diameter and roundness index of the maximum metastatic lymph node were independent risk factors of PFS in patients with stage IIIC1r CSCC (all P-values < 0.05). Nomogram based on them to predict 1- and 3-year PFS achieved C-indexes of 0.835 (95% confidence interval (CI): 0.809-0.862) and 0.789 (95%CI: 0.683-0.895) in the training and validation cohorts, respectively. Areas under ROC curves for the nomogram to predict 1- and 3-year PFS were 0.891 (95%CI: 0.829-0.954), 0.921 (95%CI: 0.861-0.981) in training cohort, and 0.902 (95%CI: 0.803-0.999), 0.885 (95%CI: 0.778-0.992) in validation cohort, respectively. Calibration curves indicated the nomogram predictions were in good agreement with actual observations. CONCLUSIONS: The nomogram based on MRI and clinical features has high accuracy and stability in predicting PFS of patients with stage IIIC1r CSCC.

[The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia].

Objective: To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial. Methods: We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models. Results: The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD(3)) after induction therapy was independently associated with relapse risk (HR=2.535, 95%CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk (HR=1.869, 95%CI 1.034-3.379, P=0.039). Based on MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % (P<0.001) and (61.6±8.3) % vs (25.5±6.5) % (P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS (HR=3.937, 95%CI 1.975-7.850, P<0.001) and CIR (HR=4.037, 95%CI 2.095-7.778, P<0.001) . Conclusion: The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

[Drug research and development and unmet needs for advanced-stage hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and is a global health challenge. Radical surgical resection is the most effective method to achieve long-term survival for HCC. Regrettably, the vast majority of HCC patients lose the opportunity for radical resection at the time of diagnosis due to advanced tumors or poor liver reserve capacity. HCC is resistant to conventional chemotherapy, and in the past, there have been no definite and effective systemic therapeutic drugs. Fortunately, over the last decade, the research and development of molecular targeted therapy and immunotherapy drugs for HCC have made rapid progress, and a variety of drugs and combination therapy regimens have been successively approved for clinical use. However, the overall therapeutic effect is still not ideal and needs further improvement.

[Correlation between the mutation spectrum of the UGT1A1 gene and clinical phenotype in patients with inherited hyperunconjugated bilirubinemia].

Objective: To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia. Methods: Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using χ(2) testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using t-test. Results: 112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups (F=0.652, P=0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 (n=10) and TA7/TA7 (n=14) mutations were statistically significant in TBil (t=2.143, P=0.043). The c.211G>A (p.G71R) heterozygous (n=9) and isolated (n=15) mutation had no statistical significance in TBil (t=0.382, P=0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups (F=270.992, P<0.001). There was no statistically significant difference (χ(2)=3.317, P=0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. Conclusion: The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.

Correlation between neuregulin receptor degradation protein-1 and Crohn's disease.

Neuregulin receptor degradation protein-1 (Nrdp1) is a newly discovered E3 ligase that plays a role in the apoptosis process of multiple diseases. Previous studies has shown that Nrdp1 exerted a proapoptotic effect in cardiac diseases. The purpose of this study is to investigate the potential involvement of Nrdp1 in the pathological processes of inflammatory bowel disease (IBD). To create a mouse model of experimental colitis, trinitrobenzenesulfonic acid (TNBS) was administered and the severity of colitis was assessed based on changes in weight and histological scores. Using Western blot and immunohistochemistry, significant increase in Nrdp1 expression was observed in intestinal epithelial cells (IECs). This was accompanied with the up-regulation of cleaved PARP and active caspase-3 in IECs, indicating a potential function in IECs. To study this further, we built an in vitro model of tumor necrosis factor-alpha (TNF-α)-induced apoptosis using human IEC line HT-29 cells. When Nrdp1 was knocked down, a decrease in apoptosis was observed, suggesting that Nrdp1 may play a proapoptotic role in IEC apoptosis. The mechanism behind this phenomenon is associated with the suppression of downstream targets of Nrdp1, such as protein kinase B (AKT). Furthermore, immunohistochemistry analysis in patients with Crohn's disease (CD) and normal controls supported the same results as observed in experimental colitis. We conclude that Nrdp1 may be a promising new therapeutic target for ameliorating IBD in humans.

[Minimal residual disease assessment and progress in multiple myeloma].

With the rapid iteration of multiple myeloma therapeutics over the last two decades, as well as increasing remission rates and depth of remission in patients, traditional methods for monitoring disease response are insufficient to meet the clinical needs of new drugs. Minimal residual disease (MRD) is a more sensitive test for determining the depth of response, and data from multiple clinical trials and meta-analyses show that a negative MRD correlates with a better prognosis than a traditional complete response. MM is at the forefront of MRD evaluation and treatment. MRD detection methods have been continuously updated. The current MRD assessment has three dimensions: bone marrow-based MRD testing, MRD testing based on images of residual metabolic of focal lesions, and peripheral blood-based MRD testing. The various MRD assessment methods complement one another. The goal of this article is to discuss the currently used MRD assays, the progress, and challenges of MRD in MM, and to provide a reference for clinicians to better use the techniques.

[Role of neoadjuvant rectal score in prognosis and adjuvant chemotherapy decision-making in locally advanced rectal cancer following neoadjuvant short-course radiotherapy and consolidation chemotherapy].

Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

DDR2 signaling and mechanosensing orchestrate neuroblastoma cell fate through different transcriptome mechanisms.

The extracellular matrix (ECM) regulates carcinogenesis by interacting with cancer cells via cell surface receptors. Discoidin Domain Receptor 2 (DDR2) is a collagen-activated receptor implicated in cell survival, growth, and differentiation. Dysregulated DDR2 expression has been identified in various cancer types, making it as a promising therapeutic target. Additionally, cancer cells exhibit mechanosensing abilities, detecting changes in ECM stiffness, which is particularly important for carcinogenesis given the observed ECM stiffening in numerous cancer types. Despite these, whether collagen-activated DDR2 signaling and ECM stiffness-induced mechanosensing exert similar effects on cancer cell behavior and whether they operate through analogous mechanisms remain elusive. To address these questions, we performed bulk RNA sequencing (RNA-seq) on human SH-SY5Y neuroblastoma cells cultured on collagen-coated substrates. Our results show that DDR2 downregulation induces significant changes in the cell transcriptome, with changes in expression of 15% of the genome, specifically affecting the genes associated with cell division and differentiation. We validated the RNA-seq results by showing that DDR2 knockdown redirects the cell fate from proliferation to senescence. Like DDR2 knockdown, increasing substrate stiffness diminishes cell proliferation. Surprisingly, RNA-seq indicates that substrate stiffness has no detectable effect on the transcriptome. Furthermore, DDR2 knockdown influences cellular responses to substrate stiffness changes, highlighting a crosstalk between these two ECM-induced signaling pathways. Based on our results, we propose that the ECM could activate DDR2 signaling and mechanosensing in cancer cells to orchestrate their cell fate through distinct mechanisms, with or without involving gene expression, thus providing novel mechanistic insights into cancer progression.

Comprehensive genomic profiling to identify actionable alterations for breast cancer brain metastases in the Chinese population.

BACKGROUND: Breast cancer brain metastasis (BCBM) is a crucial issue in the treatment of breast cancer and is associated with poor prognosis. Therefore, novel therapeutic targets are urgently needed in clinical practice. In this study, we aimed to identify potential actionable targets in brain metastases (BMs) utilising the FoundationOne® CDx (F1CDx). PATIENTS AND METHODS: Formalin-fixed paraffin-embedded archived specimens including 16 primary breast tumours (PTs), 49 BCBMs and 7 extracranial metastases (ECMs) from 54 patients who underwent surgery for BCBM were tested using F1CDx. Tumour-infiltrated lymphocytes (TILs) of BMs were also tested using haematoxylin-eosin staining. RESULTS: The median tumour mutational burden (TMB) and TILs in BMs were 5.0 (range 0-29) mut/Mb and 1.0% (range 0%-5.0%), respectively. High TMB (≥10 mut/Mb) was detected in four cases (8%). Genomic alterations (GAs) were detected in all samples. The top-ranked somatic mutations in BMs were TP53 (82%), PIK3CA (35%), MLL2 (22%), BRCA2 (14%) and ATM (14%) and the most prevalent copy number alterations were ERBB2 (64%), RAD21 (36%), CCND1 (32%), FGF19 (30%) and FGF3 (30%). The most prevalent GAs were relatively consistent between paired PTs and BMs. Actionable GAs were detected in 94% of all BMs. Consistent rate in actionable GAs was 38% (6/16) between paired PTs/ECMs and BMs. Compared to matched PTs/ECMs, additional actionable GAs (BRAF, FGFR1, PTEN, KIT and CCND1) were discovered in 31% (5/16) of the BMs. CONCLUSIONS: TMB and TILs were relatively low in BCBMs. Comparable consistency in actionable GAs was identified between BCBMs and matched PTs/ECMs. It was, therefore, logical to carry out genomic testing for BCBMs to identify potential new therapeutic targets when BCBM specimens were available, as ∼31% of samples carried additional actionable GAs.

[The clinical significance of lateral pelvic sentinel lymph node biopsy using indocyanine green fluorescence navigation in laparoscopic lateral pelvic lymph node dissection].

Objectives: This study aims to explore the clinical significance of lateral pelvic sentinel lymph node biopsy (SLNB) using indocyanine green (ICG) fluorescence navigation in laparoscopic lateral pelvic lymph node dissection (LLND) and evaluate the accuracy and feasibility of this technique to predict the status of lateral pelvic lymph nodes (LPLNs). Methods: The clinical and pathological characteristics, surgical outcomes, lymph node findings and perioperative complications of 16 rectal cancer patients who underwent SLNB using ICG fluorescence navigation in laparoscopic LLND in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during April 2017 and October 2022 were retrospectively collected and analyzed. The patients did not receive preoperative neoadjuvant radiotherapy and presented with LPLNs but without LPLN enlargement (MRI showed the maximum short axes of the LPLNs were ≥5 mm and <10 mm at first visit). Results: All 16 patients were successfully performed SLNB using ICG fluorescence navigation in laparoscopic LLND. Three patients underwent bilateral LLND and 13 patients underwent unilateral LLND. The lateral pelvic sentinel lymph nodes (SLNs) were clearly fluorescent before dissection in 14 patients and the detection rate of SLNs for these patients was 87.5%. Lateral pelvic SLN metastasis was diagnosed in 2 patients and negative results were found in 12 patients by frozen pathological examinations. Among the 14 patients in whom lateral pelvic SLNs were detected, the dissected lateral pelvic non-SLNs were all negative. All dissected LPLNs were negative in two patients without fluorescent lateral pelvic SLNs. The specificity, sensitivity, negative predictive value, and accuracy was 85.7%, 100%, 100%, and 100%, respectively. Conclusions: This study indicates that lateral pelvic SLNB using ICG fluorescence navigation shows promise as a safe and feasible procedure with good accuracy. This technique may replace preventive LLND for locally advanced lower rectal cancer.

[Comparison of short-term safety of two anastomotic techniques when resecting Siewert type II adenocarcinoma of the esophagogastric junction: a multicenter retrospective cohort study].

Objective: In this study, we aimed to compare the short-term safety of two digestive tract reconstruction techniques, laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis, following radical resection of Siewert Type II adenocarcinoma of the esophagogastric junction. Methods: In this retrospective cohort study, we analyzed relevant clinical data of 139 patients who had undergone radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. These included 89 patients treated at the First Affiliated Hospital of Air Force Medical University from November 2021 to July 2023, 36 patients treated at the First Affiliated Hospital of Xi'an Jiaotong University from December 2020 to June 2021, and 14 patients treated at the Yuncheng Central Hospital in Shanxi Province from September 2021 to November 2022. The group consisted of 107 men (77.0%) and 32 women (23.0%) of mean age 62.5±9.3 years. Forty-eight patients underwent laparoscopic total abdominal overlap anastomosis (overlap group), and 91 laparoscopic-assisted end-to-side anastomosis (end-to-side group). Clinical data, surgical information, pathological findings, postoperative recovery, and related complications were compared between the two groups. Results: There were no significant differences in general clinical data between the overlap and end-to-side anastomosis groups (all P>0.05), indicating comparability. There was no significant difference in operation time (267.2±60.1 minutes vs. 262.8±70.6 minutes, t=0.370, P=0.712). However, the intraoperative blood loss in the overlap group (100 [50, 100] mL) was significantly lower compared to the end-to-side group (100[50, 175] mL, Z=2.776, P=0.005). Compared to the end-to-side group, longer distances between the tumor and distal resection margin proximal(1.7±1.0 cm vs. 1.3±0.9 cm, t=2.487, P=0.014) and the tumor and distal resection margin (9.5±2.9 cm vs. 7.9±3.5 cm, t=2.667, P=0.009) were achieved in the overlap group. Compared with the end-to-side group, the overlap group achieved significantly earlier postoperative ambulation (1.0 [1.0, 2.0] days vs. 2.0 [1.0, 3.0] days, Z=3.117, P=0.002), earlier time to first drink (4.7±2.6 days vs. 6.2±3.0 days, t=2.851, P=0.005), and earlier time to first meal (6.0±2.7 days vs. 7.1±3.0 days, t=2.170, P=0.032). However, the hospitalization costs were higher in the overlap group (113, 105.5±37, 766.3) yuan vs. (97, 250.2±27, 746.9) yuan; this difference is significant (t=2.818, P=0.006). There were no significant differences between the two groups in postoperative hospital stay, total number of lymph nodes cleared, or time to first postoperative flatus (all P>0.05). The incidence of surgery-related complications was 22.9%(11/48) in the overlap group and 19.8% (18/91) in the end-to-side group; this difference is not significant (χ²=0.187, P=0.831). Further comparison of complications using the Clavien-Dindo classification also showed no significant differences (Z=0.406, P=0.685). Conclusions: Both laparoscopic total abdominal overlap anastomosis and laparoscopic-assisted end-to-side anastomosis are feasible for radical surgery for Siewert Type II esophagogastric junction adenocarcinoma. Laparoscopic total abdominal overlap anastomosis achieves longer proximal and distal resection margins and better postoperative recovery; however, end-to-side anastomosis is more cost-effective.

TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes.

BACKGROUND: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate containing cytotoxic SN-38, the active metabolite of irinotecan. SG received accelerated US Food and Drug Administration approval for locally advanced (LA) or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and a checkpoint inhibitor, based on cohort 1 of the TROPHY-U-01 study. Mutations in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene are associated with increased adverse events (AEs) with irinotecan-based therapies. Whether UGT1A1 status could impact SG toxicity and efficacy remains unclear. PATIENTS AND METHODS: TROPHY-U-01 (NCT03547973) is a multicohort, open-label, phase II registrational study. Cohort 1 includes patients with LA or mUC who progressed after platinum- and checkpoint inhibitor-based therapies. SG was administered at 10 mg/kg intravenously on days 1 and 8 of 21-day cycles. The primary endpoint was objective response rate (ORR) per central review; secondary endpoints included progression-free survival, overall survival, and safety. Post hoc safety analyses were exploratory with descriptive statistics. Updated analyses include longer follow-up. RESULTS: Cohort 1 included 113 patients. At a median follow-up of 10.5 months, ORR was 28% (95% CI 20.2% to 37.6%). Median progression-free survival and overall survival were 5.4 months (95% CI 3.5-6.9 months) and 10.9 months (95% CI 8.9-13.8 months), respectively. Occurrence of grade ≥3 treatment-related AEs and treatment-related discontinuation were consistent with prior reports. UGT1A1 status was wildtype (∗1|∗1) in 40%, heterozygous (∗1|∗28) in 42%, homozygous (∗28|∗28) in 12%, and missing in 6% of patients. In patients with ∗1|∗1, ∗1|∗28, and ∗28|∗28 genotypes, any grade treatment-related AEs occurred in 93%, 94%, and 100% of patients, respectively, and were managed similarly regardless of UGT1A1 status. CONCLUSIONS: With longer follow-up, the ORR remains high in patients with heavily pretreated LA or mUC. Safety data were consistent with the known SG toxicity profile. AE incidence varied across UGT1A1 subgroups; however, discontinuation rates remained relatively low for all groups.

[Prognostic value of the Second Revision of the International Staging System in patients with newly diagnosed transplant-eligible multiple myeloma].

Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

[Clinical characteristics of posterior malleolus fracture in adults].

Objective: To explore the latest clinical characteristics and development trends of posterior malleolus fracture. Methods: Clinical information of inpatients with posterior malleolus fracture in Shanghai Tongji Hospital and Karamay Central Hospital from January 2014 to December 2022 were reviewed and collected. The imaging data of patients were acquired using the Picture Archiving and Communication Systems. A statistical analysis was performed as to gender, current age, year of admission, injury mechanism, fracture type, and posterior malleolus fracture classification. Moreover, a comparative analysis was conducted on the injury mechanisms and morphological differences of posterior malleolus fracture at different periods, regions, and age groups. Results: A total of 472 patients (210 patients from Shanghai Tongji Hospital and 262 patients from Karamay Central Hospital) with posterior malleolus fracture with a mean age of (48.7±15.6) years were included in this study. The peak of posterior malleolus fracture occurs in the age group of 50-59 years. The injury mechanisms mainly involve low-energy fall and sprain (411 cases, 87.1%), followed by traffic accidents (52 cases, 11.0%), and fall injury from height (9 cases, 1.9%). The number of cases according to different fracture types showed the following descending order: trimalleolar fracture-supination extorsion (335 cases, 71.0%), bimalleolar fracture (60 cases, 12.7%), trimalleolar fracture-pronation extorsion (43 cases, 9.1%), posterior malleolus+tibial shaft fracture (19 cases, 4.0%), simple posterior malleolus fracture (15 cases, 3.2%). The numbers of cases corresponding to the Haraguchi Ⅰ, Ⅱ and Ⅲ type of posterior malleolus fractures was 369 (78.2%), 49 (10.4%), and 54 (11.4%), respectively. The Tongji ⅡA type represented the highest number of cases (249 cases, 52.8%), followed by the ⅡB type (120 cases, 25.4%), Ⅰ type (54 cases, 11.4%), ⅢB type (36 cases, 7.6%), and ⅢA type (13 cases, 2.8%). However, no obvious statistical difference was observed in the injury mechanism, Haraguchi classification, and Tongji classification of posterior malleolus fractures among different years and regions from the year of 2014 to 2022 (all P>0.05). Conclusions: The injury mechanism of posterior malleolus fracture mainly involves low-energy fall and sprain cases. The trimalleolar fracture-supination extorsion, Haraguchi Ⅰ type and Tongji ⅡA type of posterior malleolus fracture are predilection fracture types, and all present an obvious incidence peak in the age group of 50-59 years. There has been no significant change in the development trend of clinical characteristics of posterior malleolus fractures in recent years.