Fruquintinib is a highly selective, oral inhibitor of all three vascular endothelial growth factor receptors (-1, -2, and -3) that was approved, including in China, the United States, and the European Union, for the treatment of previously treated metastatic colorectal cancer (mCRC). The efficacy of fruquintinib for mCRC has been consistently demonstrated in randomized, double-blind, Phase 3 clinical studies, including FRESCO (NCT02314819), which enrolled patients in China, and FRESCO-2 (NCT04322539), which enrolled patients across 14 countries in North America, Europe, Asia, and Australia. In both studies, patients were randomized 2:1 to receive oral fruquintinib 5 mg or a matching placebo once daily, 3 weeks on, 1 week off, in 28-day cycles, plus best supportive care, until progression or unacceptable toxicity. Both FRESCO and FRESCO-2 met their primary endpoints, demonstrating significant improvements in overall survival (OS) with fruquintinib versus placebo: in FRESCO (fruquintinib: n = 278; placebo: n = 138), median OS was 9.3 with fruquintinib versus 6.6 months with placebo (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.51-0.83; p < 0.001); in FRESCO-2 (fruquintinib: n = 461; placebo: n = 230), median OS was 7.4 with fruquintinib versus 4.8 months with placebo (HR, 0.66; 95% CI, 0.55-0.80; p < 0.001). The most common any-grade treatment-emergent adverse events with fruquintinib (incidence ≥ 20% in either study, excluding laboratory abnormalities) were hypertension, palmar-plantar erythrodysesthesia, proteinuria, dysphonia, diarrhea, asthenia, decreased appetite, hypothyroidism, and fatigue. This mini-review summarizes the mechanism of action, pharmacokinetics, key clinical trials, and clinical efficacy and safety data for fruquintinib.

Desmoid disease is a major cause of morbidity and mortality in familial adenomatous polyposis (FAP), particularly after prophylactic colorectal surgery. Although APC genotype and family history are recognized risk factors, previous sizeable studies report relative rather than absolute risks. This study aimed to quantify absolute postoperative desmoid risk in FAP patients undergoing risk-reducing colectomy, stratified by APC genotype, and to assess the modifying effect of family history.

This retrospective observational study used records from a prospectively maintained registry. Patients with an APC pathogenic variant (PV) 3' of codon 1399 were classified as high risk, and those with an APC PV 5' of (or at) codon 1399 were classified as low risk. Patients who had not undergone prophylactic colectomy, with < 5 years of postoperative follow-up, or those with a desmoid diagnosed before or at the time of surgery were excluded. Clinical records were reviewed for details of surgery, desmoid diagnosis, and family history. A positive family history was defined as a first-degree relative with genetically confirmed FAP and a diagnosis of desmoid disease (clinical and/or radiological).

Among 48 high-risk patients, 30 (63%) developed desmoid, with no significant difference between colectomy and proctocolectomy (54% versus 70%, respectively; χ2 = 1.42; P = 0.233). Family history was present in 35 of the 48 patients (73%) and increased desmoid risk relative to no family history (80% versus 15%, respectively; P < 0.01). Among the 1213 low-risk patients, 154 (12.7%) developed desmoids, with no significant effect of surgical procedure (13.9% versus 12.1% for proctocolectomy and total/partial colectomy, respectively; χ² = 0.77; P = 0.380). Family history increased desmoid risk relative to no family history (30% versus 10%, respectively; P < 0.01).

A family history of desmoid disease appears to be an important determinant of postoperative desmoid risk in FAP. Although APC PV 3' of codon 1399 does confer a high overall risk, this is largely confined to individuals with first-degree relatives with desmoid. In the absence of a family history, postoperative desmoid risk appeared relatively low regardless of genotype. This supports a more individualized approach to perioperative counselling and surgical decision-making in patients with FAP. In addition, these data highlight that patients with both a 3' APC PV and a positive family history are a particularly high-risk subgroup who may represent an appropriate target population for future chemoprevention trials.

Surgical randomized clinical trials (RCTs) have structural features that differ fundamentally from those of non-surgical trials, which may complicate appraisal using standard assessment frameworks. This methodological systematic review used rectal cancer surgery RCTs as a high-complexity exemplar to identify surgically specific methodological challenges and to examine their interaction with established tools for assessing risk of bias and certainty of evidence.

A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library on 1 November 2025. Eligible studies were RCTs evaluating surgery-related interventions for rectal cancer in adult patients, published in English from 2020 onward, with sufficient methodological detail. Included trials were categorized into predefined, mutually exclusive surgical RCT types. Methodological features were descriptively summarized and conceptually mapped to the domains of the revised Cochrane Risk of Bias (RoB 2) tool and the GRADE framework using both quantitative tabulation and narrative synthesis.

Of 1529 records identified, 45 publications reporting on 35 RCTs were included. Trials were classified into five surgical RCT categories. Surgically specific methodological challenges were most frequently observed in RoB 2 domains D2 (bias due to deviations from intended interventions) and D4 (bias in measurement of the outcome), as well as in the GRADE domain of indirectness.

This review suggests that several challenges encountered when applying RoB 2 and GRADE to surgical RCTs arise from structural characteristics of surgical trial design rather than obvious methodological shortcomings. Contextualizing standard appraisal frameworks within the realities of surgical research may allow for a more nuanced interpretation of existing evidence, inform future trial design, and support more appropriate evidence synthesis.

We aimed to stratify clinical risk among patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) treated with first-line androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT).

We retrospectively analyzed 626 patients with high-volume mHSPC treated with ARPI+ADT between November 2016 and April 2025. A multivariable Cox model for time to castration-resistant prostate cancer (TTCRPC) was developed using nine baseline characteristics, including age, hemoglobin, ECOG performance status, clinical T stage, ISUP grade group, EOD score, lung and liver metastases, and LDH, selected based on clinical relevance and prior evidence. Model discrimination and calibration were assessed using bootstrap internal validation. Patients were stratified into three risk groups based on the linear predictor, and associations with TTCRPC and overall survival (OS) were evaluated.

The median follow-up was 34.8 months. Clinical T4 stage, ISUP grade group 5, and higher LDH were independently associated with shorter TTCRPC, whereas lung metastasis was associated with longer TTCRPC. The model had an optimism-corrected C-index of 0.69. TTCRPC differed significantly across the low-, intermediate-, and high-risk groups (p < 0.001); compared with the low-risk group, the HRs were 1.48 (95% CI 1.00-2.17) for the intermediate-risk group and 4.09 (95% CI 2.90-5.77) for the high-risk group. OS also differed significantly across the three risk groups (p < 0.001).

In patients with high-volume mHSPC treated with ARPI+ADT, the model showed modest discrimination for TTCRPC and identified groups with different TTCRPC and OS outcomes. These findings suggest the presence of clinically heterogeneous subgroups within high-volume mHSPC and warrant independent validation in external cohorts.

It is not uncommon for many of the patients with oral squamous cell carcinoma (OSCC) to encounter diagnostic delays due to the similarity of their initial presentations with other jaw lesions. The present case report discusses jaw pain after a dental extraction, initially attributed to chronic osteomyelitis. After long and multiple diagnostic and prognostic procedures, the patient had mandibulectomy, neck dissection, and reconstruction for histopathologically substantiating stage pT4a OSCC. Delays in treatment may necessitate more aggressive interventions. Improved clinical awareness, telemedicine, enhanced doctor-patient communication, and refined diagnostic protocols contribute to better outcomes. This case highlights the diagnostic challenges of OSCC, particularly its ability to mimic chronic osteomyelitis. A delayed diagnosis emphasises the need for early recognition and intervention. While imaging aids in initial assessment, histopathology is crucial for a definitive diagnosis.

Thoracoscopy-guided thoracic paravertebral block (TG-TPVB) is a new analgesia technique; however, the duration of a single TG-TPVB is short. Esketamine combined with local anesthetics can prolong the duration of nerve block. This study compared the analgesic efficacy of three doses of esketamine combined with ropivacaine for TG-TPVB in patients undergoing thoracoscopic radical resection for lung cancer.

160 patients were randomly allocated into the control, S1, S2, and S3 groups. All patients received TG-TPVB with 20 mL of study solution. The control group received 0.375% ropivacaine alone, whereas the S1, S2, and S3 groups received 0.375% ropivacaine combined with esketamine at doses of 0.1, 0.2, and 0.3 mg/kg, respectively. The time to first patient-controlled intravenous analgesia (PCIA) demand, postoperative numerical rating scale (NRS) pain scores, sufentanil consumption, effective PCIA demands, recovery outcomes, and adverse events were compared between the four groups.

The time to first PCIA demand in the three esketamine groups were longer than in the control group. However, S2 and S3 groups were longer than S1 group. NRS pain scores in the three esketamine groups were lower than in the control group at 6, 12, 24, and 48 h postoperatively. Postoperative sufentanil consumption within 24 h, the number of effective PCIA demands and rescue analgesia administrations within 48 h were lower in the three esketamine groups than in the control group. Wake-up time was longer in the S3 group than in the control, S1, and S2 groups. The times to first ambulation and chest tube removal were shorter in the esketamine groups than in the control group (All P<0.001).

Esketamine combined with ropivacaine for TG-TPVB prolonged postoperative analgesia, reduce pain scores, reduced analgesic consumption, and facilitated recovery. Esketamine at 0.2 mg/kg seems to show a good balance effect in many aspects.

Exosomes are nanoscale extracellular vesicles (EVs) that mediate intercellular communication by transporting proteins, lipids and nucleic acids. Their biocompatibility, low immunogenicity and intrinsic ability to protect labile cargo make them attractive therapeutic carriers. Yet their clinical translation remains constrained by heterogeneous isolation protocols, variable product purity, inefficient cargo loading, rapid systemic clearance and limited tissue-selective delivery. Engineering strategies, including parental-cell preconditioning, genetic modification, post-isolation cargo loading and surface functionalization, have improved the potency and targeting of exosome-based therapeutics but have not fully solved delivery-related bottlenecks. Microneedle (MN) systems provide a complementary solution by breaching the stratum corneum in a minimally invasive manner and depositing exosomes directly within defined tissue compartments. When integrated with dissolving, hydrogel, cryogenic, core-shell, Janus, threaded or stimulus-responsive MN architectures, exosomes can be retained locally, released in a programmed manner and protected from rapid degradation. This Review first summarizes the biological basis, source-dependent functions and engineering strategies of exosomes, and then outlines the design principles of MN platforms relevant to vesicle delivery. On this basis, we discuss representative studies in which MN systems have been explored to improve the local retention, controlled release and tissue-specific delivery of exosomes in cancer, wound repair, neurological injury, cardiovascular disease, immune-mediated disorders and other regenerative settings. We further summarize the translational barriers that remain for this emerging strategy, including vesicle characterization, potency assays, sterility control, scalable manufacturing, long-term safety, storage stability and batch-to-batch reproducibility.

Enhanced recovery after surgery (ERAS) protocols are multimodal perioperative pathways designed to reduce surgical stress, accelerate recovery, and improve resource utilization. Although ERAS principles have been increasingly adopted in microsurgery, their application in vascularized lymph node transfer (VLNT), particularly using gastroepiploic flaps, remains poorly defined. The aim of this study was to evaluate the feasibility, safety, and effectiveness of a tailored ERAS protocol in patients undergoing gastroepiploic VLNT for breast cancer-related upper extremity lymphedema.

A retrospective comparative study was conducted in patients with unilateral breast cancer-related upper extremity lymphedema (ISL Stage II-III) undergoing gastroepiploic vascularized lymph node transfer after failure of at least 6 months of conservative treatment. Patients were managed either with a conventional perioperative protocol, including nasogastric tube placement, delayed oral intake, delayed mobilization, opioid-based analgesia, and delayed initiation of complete decongestive therapy (CDT), or with a tailored ERAS-VLNT protocol incorporating early oral intake, early mobilization, opioid-sparing analgesia, avoidance of nasogastric decompression, and CDT initiation from postoperative Day 7. Outcomes included circumferential reduction rate, LYMQOL score, infection rate, flap-related complications, length of hospital stay, and hospitalization costs.

A total of 45 patients were included, with 29 in the ERAS group and 16 in the conventional group. Baseline demographic and clinical characteristics were comparable between groups. The ERAS group demonstrated a significantly shorter hospital stay (2.34 ± 0.48 vs. 5.56 ± 0.51 days, p < 0.001) and lower estimated hospitalization costs (€1400 vs. €3300, p < 0.001). Flap survival was 100% in both groups, with no flap-related complications. Circumferential reduction rate was comparable between groups (44.39% ± 10.20% vs. 47.53% ± 8.26%, p = 0.278), as were LYMQOL scores at 12 months (8.21 ± 0.73 vs. 7.93 ± 0.70, p = 0.236) and infection rates (2.62 ± 0.90 vs. 2.73 ± 0.96 episodes/year, p = 0.71).

An ERAS-based protocol tailored to VLNT is feasible and safe, and is associated with improved perioperative recovery and reduced healthcare costs without evidence of compromised surgical or functional outcomes. These findings support the integration of ERAS principles into lymphatic microsurgery and warrant further prospective validation.

Tumor and liver-related factors are well-known prognostic factors for patients with hepatocellular carcinoma (HCC). The Japanese Society of Hepatology (JSH) guidelines recommend considering liver resection (LR) for patients with multiple tumors and a tumor number ≤ 3. A previous Italian study showed that a model for end-stage liver disease (MELD) score of > 9 indicates inadequate liver function reserve in patients with HCC undergoing LR.

We used these two parameters to predict the overall survival (OS) of patients with Barcelona clinic liver cancer (BCLC) Stage B HCC who underwent LR or transcatheter arterial chemoembolization (TACE).

We consecutively enrolled patients with BCLC stage B HCC and Child-Pugh Class A liver disease underwent LR or TACE. Of these patients, 163 underwent LR and 270 underwent TACE. We used two parameters, that is, ≤ 3 nodules and a MELD score of ≤ 9, to subclassify BCLC stage B HCC patients. BCLC B1 had to occur concomitantly with two parameters, whereas for BCLC B2, meeting only one criterion was sufficient. The five-year OS of BCLC B1 patients undergoing LR was 60% and those undergoing TACE was 37% (p = 0.007). The 5-year OS of BCLC B2 patients undergoing LR was 23% and those undergoing TACE was 18% (p = 0.223).

We recommend considering LR for BCLC B1 patients, whereas TACE could be considered for BCLC B2 patients.

Tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager, has shown activity in previously treated small cell lung cancer (SCLC); however, real-world data on cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain limited. We evaluated the efficacy and safety of tarlatamab and laboratory findings associated with CRS in patients previously treated for extensive-stage SCLC.

We retrospectively analyzed 11 patients who received tarlatamab through an expanded access program between October 2024 and May 2026. Repeated laboratory measurements were analyzed using generalized estimating equations and mixed-effects models.

The objective response and disease control rates were 54.5% and 72.7%, respectively. The mean and median tumor size changes from baseline were -9.1% and -25.0%, respectively. The median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI]: 1.9-not reached) and 10.1 months (95% CI: 4.5-not reached), respectively. CRS occurred in seven patients (63.6%), with 10 events, all occurring during the first cycle and limited to Grade 1 or 2. No CRS event required tocilizumab treatment, intensive care unit admission, dose reduction, or treatment discontinuation. One patient developed Grade 3 ICANS and recovered fully. CRS events were associated with higher neutrophil percentages, lower lymphocyte percentages, and higher neutrophil-to-lymphocyte ratios than no-CRS events.

Tarlatamab shows encouraging antitumor activity and manageable toxicity in heavily pretreated Korean patients with SCLC. The neutrophil-to-lymphocyte ratio may represent an exploratory, concurrent hematologic correlate of CRS.