Current methods for detecting monoclonal (M) proteins, such as immunofixation electrophoresis (IFE), serum protein electrophoresis (SPEP) and serum free light chains (sFLC), are limited by insufficient sensitivity and suboptimal efficiency. This study evaluated the performance and supplementary value of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) for the detection of M-protein.

The M protein in the blood samples of 137 newly diagnosed plasma cell disorder (PCD) patients were detected using MALDI-TOF-MS. Using SPEP/IFE/sFLC as the gold standard, the performance of MALDI‑TOF MS was assessed; discrepant results were confirmed by urine IFE.

The cohort included multiple PCD subtypes, detailly, 116 multiple myeloma (MM, 84.7%), 7 amyloid light-chain (AL) amyloidosis (5.1%), 6 MM combined with AL amyloidosis (4.4%), 4 monoclonal gammopathy of undetermined significance (MGUS, 2.9%), and others. Serum-based MALDI-TOF-MS demonstrated a high detection rate for M-protein identification compared to SPEP, serum IFE, sFLC and urine IFE (98.5% vs. 75.9% vs. 86.9% vs. 71.5% vs. 76.0%). Plasma-based testing achieved a concordance rate of 89.1% (122/137). Using IFE/sFLC results as the gold standard, the sensitivity of MALDI-TOF-MS for the identification of κ and λ light chains (LC) was 75.8% and 80.0%, respectively. For IgG and IgA identification, the sensitivity of MALDI-TOF-MS was 93.5% (58/62) and 65.5% (19/29), respectively. Additionally, MALDI-TOF-MS detected LC glycosylation in 17 patients and other post-translational modifications (PTMs) in 4 patients. Notably, post-treatment monitoring revealed that two patients with eliminated glycosylation peaks achieved complete response, while one with persistent glycosylation had a very good partial response.

MALDI-TOF-MS is a reliable tool for M-protein detection, offering high detection rate, LC glycosylation identification, and PTM analysis. Additionally, in a small cohort, we observed that changes in the abnormal peaks detected by MALDI-TOF-MS may correlate with treatment response.

This study aimed to identify and synthesize published algorithms for identifying the initiation of a new line of therapy (LOT) for metastatic lung, breast, and colorectal cancer in real-world data (RWD).

We conducted a scoping review of published, English-language studies describing algorithms for identifying any LOTs with systemic anti-cancer therapy (SACT) for either non-metastatic or metastatic lung, breast, or colorectal cancer in RWD between January 1, 2014, and April 29, 2024. Dual reviewers independently screened titles, abstracts, and full-text articles, with disagreements resolved by a third reviewer. Data were extracted, categorized, synthesized, and summarized in narrative and tabular formats.

The review identified 25 studies, mainly (64%) from the United States. Electronic health/medical records (EHRs) were the most frequently utilized (72%) RWD source. Twenty-four studies (96%) described RWD algorithms for identifying the initiation of a new LOT for metastatic lung, breast, or colorectal cancer. In 23 studies, algorithms required observing a new, adjuvant, SACT after an "incident" metastatic diagnosis code, which had been preceded by a metastasis-free lookback period of varied duration. Three studies' algorithms required observation of the completion of non-metastatic LOTs before initiation of a new LOT for metastatic cancer. Three studies validated their algorithms.

Different algorithms are being used to identify LOT initiation for metastatic cancer. Most algorithms require an incident diagnosis of metastasis before considering subsequent SACT as newly initiated LOT for metastatic cancer. However, definitions of metastasis onset and gap duration to therapy initiation vary.

Colorectal cancer (CRC) remains a leading cause of global cancer-related morbidity and mortality. The majority of CRC cases arise through two well-established pathways: the conventional adenoma-carcinoma sequence and the serrated neoplasia pathway. Colonoscopic polypectomy significantly reduces the incidence of CRC, yet postoperative recurrence rates remain substantial, underscoring the critical role of post-polypectomy colonoscopic surveillance (PPCS). Recent updates to PPCS guidelines by major gastroenterological societies-including the US Multisociety Task Force (USMSTF), European Society of Gastrointestinal Endoscopy (ESGE), British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England (BSG/ACPGBI/PHE), and the Asia-Pacific Task Force-reflect evolving strategies for risk stratification and surveillance intervals. While all guidelines prioritize colonoscopy resources for high-risk populations and reduce burden for low-risk individuals, significant variations persist in definitions of high-risk adenomas (HRA), recommendations for surveillance intervals, and management of specific histological subtypes such as villous architecture. This review comprehensively compares these updated guidelines, highlighting consensus and discordance in clinical recommendations. Furthermore, it synthesizes evidence on multifactorial recurrence risks, encompassing baseline adenoma characteristics, patient-specific factors, and the quality of endoscopic procedures. Regarding the association with the same risk factor, traditional adenomas and serrated polyps may demonstrate heterogeneity. Understanding these elements is essential for optimizing personalized surveillance strategies and reducing recurrent adenoma burden. Finally, we hope that this review will provide decision-making support for countries lacking standalone guidelines and help clinicians navigate complex and contradictory guideline recommendations.

To evaluate the value of serum Mac-2 binding protein (M2BP) for assessment of the severity of schisto somiasis-induced liver fibrosis, so as to provide insights into non-invasive diagnosis and disease surveillance of liver fibrosis caused by schistosomiasis.

A total of 234 individuals with a history of Schistosoma japonicum infection were sampled from Xinhua Village, Lushan City, Jiangxi Province from 2019 to 2020, and 234 serum samples were collected from all participants. All participants received B-ultrasound examinations of the liver. Serum samples were categorized into four groups (grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis groups) according to B-ultrasound examination results, and then, each group was randomly divided into a receiver operating characteristic (ROC) curve group and an efficacy assessment group at a ratio of 7∶3. Serum M2BP concentration was measured in four groups using the enzyme-linked immunosorbent assay (ELISA), and differences in serum M2BP concentrations were compared with analysis of variance and Spearman correlation analysis. Serum M2BP concentration was subjected to ROC curve analysis among individuals with different grades of schistosomiasis-induced liver fibrosis in the ROC curve group to determine the optimal diagnostic threshold of M2BP concentration at different fibrosis grades, and the area under the ROC curve (AUC) was calculated to evaluate the diagnostic performance. The diagnostic accuracy was verified by comparing the accordance rate and Kappa consistency test in the efficacy assessment group.

Among 234 serum samples, there were 79 samples with grade 0 schistosomiasis-induced liver fibrosis, 87 samples with Grade Ⅰ, 46 samples with Grade Ⅱ and 22 samples with Grade Ⅲ according to the B-ultrasound examinations. The mean serum M2BP concentrations were (0.40 ± 0.31) [95% confidence interval (CI): (0.33, 0.47)], (0.64 ± 0.48) [95% CI: (0.53, 0.74)], (1.76 ± 0.58) [95% CI: (1.59, 1.93)] μg/mL and (2.56 ± 0.93) [95% CI: (2.14, 2.97)] μg/mL in the four groups, respectively (F = 150.796, P < 0.001), and the severity of schistosomiasis-induced liver fibrosis significantly positively correlated with serum M2BP concentration (rs = 0.715, P < 0. 001). The sample sizes of grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis sera were randomly allocated as follows: 55 versus 24, 61 versus 26, 32 versus 14, and 15 versus 7 in the ROC curve and efficacy assessment groups, respectively, and the serum M2BP concentrations were (0.39 ± 0.29) μg/mL and (0.42 ± 0.36) μg/mL (F = 0.196, P > 0.05), (0.59 ± 0.47) μg/mL and (0.75 ± 0.51) μg/mL (F = 1.967, P > 0.05), (1.73 ± 0.59) μg/mL and (1.85 ± 0.57) μg/mL (F = 0.417, P > 0.05), and (2.46 ± 0.64) μg/mL and (2.76 ± 1.41) μg/mL (F = 0.491, P > 0.05), respectively. ROC curve analysis showed that the optimal diagnostic thresholds of serum M2BP concentration were 0.347 86 μg/mL (AUC = 0.635, P < 0.05), 1.188 83 μg/mL (AUC = 0.938, P < 0.000 1) and 2.021 21 μg/mL (AUC = 0.821, P < 0.000 1) for grade Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis. In addition, the accordance rates between the optimal diagnostic threshold of serum M2BP and B-ultrasound examinations for predicting grade Ⅰ, Ⅱ and Ⅲ schistosomiasis-induceed liver fibrosis were 69.23%, 85.71% and 71.43% (χ2 = 1.340, P > 0.05), and the overall Kappa consistency test showed moderate consistency [Kappa = 0.608, 95% CI: (0.428, 0.788); Z = 6.609, P < 0.000 1].

Serum M2BP may serve as a potential biomarker for assessing moderate to advanced schistosomiasis-induced liver fibrosis; however, its diagnostic value for early-stage schistosomiasis-induced liver fibrosis remains limited.

Attrition of new therapies is a major concern in oncology drug development. Little is known about subsequent drug development milestones once an oncology agent has entered clinical testing in children and adolescents.

This study identified 191 cancer drugs that first entered clinical trials between 2005 and 2020 and for which patients <18 years were eligible. The authors tracked subsequent drug development and regulatory milestones through 2025. They calculated Kaplan-Meier cumulative incidence rates of reaching each milestone, and they calculated Cox hazard rates according to features of the drug and trial characteristics.

The majority (62.8%) of the 191 identified drugs were small molecule inhibitors. The majority of trials evaluated single agents (66.5%) and were multicenter trials (77.9%). At 10 years from first pediatric-eligible trials, the cumulative incidence rates of subsequent phase 1, phase 2, and phase 3 trials were 56.1%, 63.0%, and 17.7%, respectively. Of 191 drugs, 71 (37.2%) had no new trials that allowed patients <18 years of age for 5 or more years from first pediatric-eligible trial. For drugs not already approved at time of initial pediatric-eligible trial, the 10-year cumulative incidence rates for subsequent pediatric Food and Drug Administration and European Medicines Agency approval were 12.0% and 5.6%, respectively. Initial trial phase and drug regulatory status at time of initial pediatric-eligible trial were the most consistent determinants of achieving subsequent drug development milestones.

Oncology drugs entering testing in children and adolescents are at high risk of attrition, including low rates of subsequent late phase trials and pediatric regulatory approvals.

Eligibility criteria used in cancer clinical trials ensure internal validity but may restrict enrollment and limit external generalizability. The US National Cancer Institute (NCI) has recommended broader criteria, but similar guidance is lacking in China.

The authors reviewed cancer clinical trials registered on China's National Medical Products Administration (NMPA) Registration and Information Disclosure Platform between 2013 and 2021. Eligibility criteria were classified as compliant or restrictive based on the US NCI recommendations. Trends over time and associations between trial characteristics and noncompliance were analyzed.

There were 2448 cancer clinical trials investigating anticancer drugs registered in China. Eligibility criteria for performance status (PS), organ function, and comorbidities were used in 96.3%, 74.7%, and 95.3% of trials, respectively; overall, 97.0% used at least one restrictive criterion beyond NCI's recommendations. The median number of restrictive criteria used was two (interquartile range [IQR], 1-3) for trials approved in 2013-2015, three (IQR, 2-4) for trials approved in 2016-2018, and three (IQR, 2-4) for trials approved in 2019-2021 (p < .001). Noncompliance became more frequent for PS (p = .000), cardiac function (p = .005), and prior/concurrent malignancies (p = .018) over time.

These findings highlight a need for more inclusive and modernized eligibility criteria for the advancement of cancer clinical trials in China.

Anastomotic leak (AL) remains one of the most feared complications following rectal surgery in stable patients with localized abscesses or contained leaks, nonoperative approaches may be considered, including broad-spectrum antibiotics, image-guided percutaneous drainage, transanal lavage and endoluminal vacuum therapy (EVT).

The procedure is performed under sedation with the patient in the left lateral Sims position. After assessing the defect location and size, a standard endoscope is introduced, and a guidewire is used to measure the cavity length, the distal end of the cavity. A sponge is prepared to cover the distal portion of the defect. The catheter tip remains sponge-free but is perforated and positioned at the apex of the cavity using the over-the-guidewire technique or by direct placement with endoscopic large grasping forceps.

We applied this method to a total of 3 patients. We applied it twice to the first two patients and three times to the third patient. In one patient, the abscess and sinus condition improved. In two patients, the sinus closed completely. In three patients, the opening at the anastomosis was almost completely repaired after 3 sessions. No complications occurred during the procedures.

Modified EVT is a cost-effective, easy-to-assemble and patient-specific version of traditional vacuum therapy. Its ability to accommodate irregular leakage spaces allows for more efficient negative-pressure application, accelerates cavity collapse and granulation and improves patient comfort by allowing for longer change intervals. This technique can broaden access to EVT and improve outcomes in selected patients.

After a median study follow-up of 36.6 months, first-line pembrolizumab plus chemotherapy numerically improved overall survival (OS) and progression-free survival (PFS) versus placebo plus chemotherapy in Japanese participants with advanced esophageal cancer in the phase 3 KEYNOTE-590 study. The 5-year follow-up is presented.

Participants with previously untreated advanced esophageal cancer were randomly assigned 1:1 to pembrolizumab 200 mg or placebo every 3 weeks up to 35 cycles plus chemotherapy (cisplatin 80 mg/m² and 5-fluorouracil 800 mg/m²/day). Primary end points were OS and PFS per RECIST v1.1 by investigator; objective response rate (ORR) and safety were secondary. The data cutoff date was July 10, 2023.

In total, 141 of 794... participants were enrolled in Japan. Median study follow-up was 60.6 months (range, 53.8-69.7). Median OS was 17.7 months (95% CI, 13.9-28.5) with pembrolizumab plus chemotherapy versus 11.7 months (95% CI, 9.5-19.0) with placebo plus chemotherapy (HR, 0.65; 95% CI, 0.45-0.94); 60-month rates were 24.0% and 8.5%. Median PFS was 6.3 months (95% CI, 6.0-8.2) versus 6.0 months (95% CI, 4.2-6.2) (HR, 0.57; 95% CI, 0.39-0.83); 60-month rates were 16.9% and 0%. ORRs were 56.8% (95% CI, 44.7-68.2) and 38.8% (95% CI, 27.1-51.5). The median DOR was 8.3 months for pembrolizumab plus chemotherapy and 6.1 months for placebo plus chemotherapy. No new treatment-related adverse events occurred since the prior analysis.

After a median follow-up of 5 years, pembrolizumab plus chemotherapy continues to provide long-term survival outcomes among Japanese participants with advanced esophageal cancer. No new safety signals were observed. Clinical trial registration ClinicalTrials.gov, NCT03189719.

Chimeric Antigen Receptor (CAR) T-cell therapy has transformed the treatment landscape for B-cell malignancies, particularly in relapsed and refractory leukemia. However, conventional CAR constructs targeting CD19 or CD20 often result in off-tumor toxicity due to shared antigen expression on healthy B-cells. CD179a, a novel leukemia-associated antigen with limited expression on normal tissues, presents a promising alternative target for safer and more specific immunotherapy.

A 5th-generation CAR construct targeting CD179a was engineered and transfected into human T-cells to assess its antileukemic efficacy. Functional characterization was performed using the JM1-VRL-10,423 B-cell leukemia cell line. Post-transfection, cytotoxic activity, apoptosis induction, gene expression, and tumor cell viability were quantified. To evaluate safety, CD179a-CAR T-cells were also co-cultured with normal human peripheral blood mononuclear cells (PBMCs). Additionally, the in vivo efficacy of CD179a-directed CAR T-cells was tested in a xenograft model of B-cell leukemia, using mice transplanted with CD179a+ tumor cells.

In vitro, CD179a-targeted CAR T-cells demonstrated potent cytotoxicity, reducing leukemia cell viability to 44.22% after 72 h, superior to both CD3/CD28-activated T-cells and 5-Fluorouracil (5-FU). Apoptosis assays confirmed early apoptotic induction in 54.3% of leukemia cells. Importantly, negligible cytotoxic effects were observed in PBMCs, indicating selective targeting. In the xenograft model, CD179a-CAR T-cells significantly reduced the expression of CD179a in leukemic cells compared to controls. Gene expression profiling further validated apoptosis pathway activation.

These findings highlight the promising antileukemic potential of CD179a-directed CAR T-cells, combining high specificity with a favorable safety profile. This in vitro and in vivo study supports the advancement of CD179a-CAR T-cell therapy as a next-generation immunotherapeutic strategy for B-cell leukemias, warranting further preclinical and clinical development.

Patients with hepatocellular carcinoma (HCC) have an unmet need for new therapies that improve survival. This phase II trial investigated the efficacy and safety of ociperlimab and tislelizumab plus BAT1706 (a bevacizumab biosimilar) in patients with first-line HCC.

In this phase II, multicenter, randomized, multi-arm, open-label trial, patients with advanced HCC received ociperlimab and tislelizumab plus BAT1706 (Arm A) or tislelizumab plus BAT1706 (Arm B). The primary objective was to evaluate efficacy using objective response rate (ORR) assessed by the investigator per RESIST v1.1 for Arms A and B.

94 patients were randomized to Arm A (N = 62) and Arm B (N = 32). Confirmed ORR (95% confidence interval) was 37.1% (25.2-50.3) for Arm A and 40.6% (23.7-59.4) for Arm B. In Arms A and B, respectively, 90.3% and 80.6% of patients experienced treatment-related treatment-emergent adverse events (TEAEs), 59.7% and 32.3% experienced Grade ≥ 3 treatment-related TEAEs and 22.6% and 9.7% experienced treatment-related TEAEs leading to treatment discontinuation. Immune-mediated adverse events were reported in 50.0% of patients in Arm A and 45.2% of patients in Arm B. Infusion-related reactions occurred in a single patient in Arm A.

In patients with advanced HCC, tislelizumab plus BAT1706 demonstrated promising ORR, while adding ociperlimab was not associated with improved efficacy. The safety profile of ociperlimab and tislelizumab plus BAT1706 was tolerable and manageable, with no new safety signals identified.

ClinicalTrials.gov: NCT04948697 (September 20, 2021).