Annals of Surgical Oncology最新文献

Background: Osteosarcoma is a malignant bone tumor primarily composed of interstitial cells; there is an urgent need to develop effective treatments to improve patient prognosis. Traditional Chinese medicine offers a promising direction for research. This study explores the inhibitory effects and mechanisms of eupatilin on osteosarcoma, as well as the feasibility of using exosomes loaded with eupatilin in the treatment of osteosarcoma.

Methods: The cell counting kit-8 (CCK-8) assay was utilized to determine the optimal experimental concentration of eupatilin and assess its effect on cell proliferation. Cell apoptosis, migration, and invasion were evaluated through flow cytometry, wound healing assay, transwell assay, and colony formation assay. The expression of neighbor of BRCA1 gene 2 (NBR2), microRNA-129-5p (miR-129-5p), and FKBP prolyl isomerase 11 (FKBP11) were assessed using real-time quantitative polymerase chain reaction and Western blot. Extracellular exosomes from bone marrow mesenchymal stem cells were extracted via ultracentrifugation. Exosomes overexpressing miR-129-5p were obtained by transfecting the stem cells, and exosomes loaded with eupatilin were prepared through co-incubation. The inhibitory effects of different exosome treatments were observed.

Results: Cytological experiments demonstrated that eupatilin significantly enhances the apoptosis rate of osteosarcoma cells, suppresses cell viability, and markedly diminishes the capacities for colony formation, migration, and invasion. PCR and WB analyses revealed that the expression levels of NBR2, FKBP11 gene, and protein were notably reduced, whereas the expression level of miR-129-5p was significantly elevated. Exosome-based therapy exhibited a pronounced inhibitory effect on osteosarcoma cells.

Conclusion: Eupatilin exerts a reliable inhibitory effect on osteosarcoma cells through the NBR2/miR-129-5p/FKBP11 regulatory axis. Exosomes can effectively carry both eupatilin and miR-129-5p, enhancing their therapeutic efficacy.

Background: Solitary pulmonary nodules in postoperative pancreatic cancer patients pose a diagnostic challenge in distinguishing primary lung cancer (PLC) from pulmonary metastasis (PM). KRAS mutation analysis is a potential tool for distinguishing these entities.

Methods: A retrospective study of 17 patients who underwent pulmonary resection after pancreatic cancer surgery was conducted. Paired pancreatic and pulmonary tumor samples were analyzed for KRAS mutations. PDX1 expression was assessed by immunohistochemistry. Preoperative clinical factors were evaluated using KRAS mutation-based classification as the reference.

Results: KRAS mutations were discordant between pancreatic and pulmonary tumors in nine patients (53%), leading to a diagnosis of PLC. KRAS G12R concordance was observed in three cases, confirming PM. Five cases with KRAS G12D or G12V concordance could not be definitively classified. KRAS mutation analysis identified more PLC cases than pathological diagnosis. PDX1 expression was found in both PM and some PLC cases, as well as in lung invasive mucinous adenocarcinoma cases without pancreatic cancer history, limiting its diagnostic value. Lymphovascular invasion in the pancreatic tumor was significantly associated with PM.

Conclusions: KRAS mutation analysis of both pancreatic tumor and lung tumor is useful for distinguishing solitary pulmonary nodules in postoperative pancreatic cancer patients. KRAS mutation analysis identified PLC more frequently than conventional pathological diagnosis.

Background: For stage IVB gastric cancer, recently, systemic cancer therapy (including cytotoxic chemotherapy, immune checkpoint inhibitors, and molecular targeted agents) is the standard treatment based on biomarker testing. If these treatments are successful and the tumor becomes resectable, conversion surgery may be considered, though its significance remains unclear. In cases showing clinical complete response (cCR), the necessity of surgery is further debated.

Methods: This retrospective single-center study included patients with cStage IVB gastric cancer who received chemotherapy or systemic cancer therapy, regardless of undergoing conversion surgery, between 2013 and 2023. Patients were stratified by objective tumor response on imaging (cCR or others). Those achieving cCR were further divided into two groups: non-OP (follow-up without surgery) and OP (underwent conversion surgery) for survival comparison.

Results: Among 1591 patients treated with systemic chemotherapy, 51 (3.2%) achieved cCR (33 non-OP; 18 OP). In the cCR cohort, the median follow-up was 57 months. The 3-year overall survival (OS) was 97% in the non-OP group and 86% in the OP group (P = 0.44), respectively. Among the entire population, conversion surgery was performed in 121 patients (7.6%), in whom pathological CR (pCR) was seen in 17 (14%). This included 10 patients with cCR and seven without cCR. Three-year OS of pCR patients was 93%.

Conclusions: The results suggested the potential for long-term survival without surgery in patients showing cCR. However, further investigation is needed regarding accurate methods to assess tumor disappearance.

Background: Owing to better technique and perioperative care, 30- and 90-day mortality after hepatectomy has improved. However, little is known about survival in the first year after hepatectomy.

Patients and methods: Patients (age > 18) who underwent hepatectomy for any indication between 1991-2018 at a single institution were identified. Univariable and multivariable logistic regression were used to assess the relationship between clinical factors and death within 1 year for all patients and for patients who underwent hepatectomy for colorectal liver metastases (CRLM).

Results: This study included 6191 patients, of which 54% had CRLM. The 1-year survival was 89.9% (95%CI:89.1-90.7%). For patients who survived to 90 days, the probability of survival until 1 year was 92.2% (95%CI:91.9-92.5%). Malignancy had the strongest association with 1-year mortality (11% versus 2%, OR:5.82, 95%CI:2.13-15.88, p < 0.001), followed by major complications (22% versus 7%, OR:2.84, 95%CI:2.31-3.49, p < 0.001) and open approach (11% versus 3%, OR:2.06, 95%CI:1.06-3.98, p = 0.032). In the CRLM subset, the 1-year death rate was 7.6% (95%CI:6.7-8.6%). Major complications (17% versus 5%, OR:2.94, 95%CI:2.10-4.12, p < 0.001), 1-year recurrence (11% versus 5%, OR:2.78, 95%CI:1.97-3.91, p < 0.001), 4+ liver lesions (12% versus 7%, OR:2.12, 95%CI:1.46-3.09, p < 0.001) and hepatitis B/C (20% versus 7%, OR:3.47, 95%CI:1.31-9.16, p = 0.012) were associated with death at 1 year for this subset.

Conclusions: The 1-year mortality after hepatectomy is substantial, with 1 out of 10 patients dying within 1 year of surgery. Unlike the 30- and 90-day mortality, which capture technical or perioperative causes of death, 1-year mortality may serve as a more comprehensive postoperative outcome, by more broadly capturing postsurgical events and disease progression.

Background: Preoperative anemia and transfusion are common in gastric cancer surgery and have been associated with adverse short-term outcomes. Their impact on long-term oncologic prognosis remains unclear. We aimed to assess the association between preoperative anemia, perioperative red blood cell transfusion, and disease-free survival (DFS) after gastrectomy.

Patients and methods: This was a prespecified long-term analysis of the prospective POWER4 multicenter cohort conducted across 72 Spanish hospitals. Patients undergoing elective gastrectomy for gastric cancer between 2019 and 2020 were followed for ≥ 36 months. DFS was defined as time from surgery to recurrence or death. Primary exposures were preoperative anemia (World Health Organization criteria) and perioperative transfusion (within 72 h). Analyses included Kaplan-Meier estimates, multivariable Cox regression, logistic regression for delayed or omitted adjuvant chemotherapy (RIOT), and causal mediation analysis. Generalized additive models (GAMs) explored nonlinear associations between hemoglobin and DFS.

Results: Among 386 patients, 47% had anemia and 28% received transfusion. In 368 with complete follow-up, DFS event rates ranged from 13% (no anemia/no transfusion) to 38% (anemia + transfusion) (p < 0.001). Both exposures were associated with DFS in univariable models but lost significance after adjustment. No hemoglobin threshold was identified. Among 149 eligible patients, RIOT was delayed or omitted in 41%, with neither exposure as independent predictors. Mediation analysis suggested transfusion explained 26% of the effect of anemia on DFS, though not significantly.

Conclusions: Anemia and transfusion were associated with adverse unadjusted outcomes, but not independently. This supports interpreting anemia as a marker of vulnerability rather than a modifiable risk factor for recurrence.

Background: The postoperative prognosis of locally advanced colorectal cancer (LACRC) exhibits significant heterogeneity. However, conventional models for predicting disease-free survival (DFS) often lack the necessary precision. Therefore, we aim to develop and validate time-to-event machine learning (ML) models for predicting DFS in patients with LACRC, ultimately improving prognostic accuracy.

Patients and methods: This multicenter cohort study enrolled 456 patients with LACRC from three medical centers. A training cohort consisting of 350 patients was formed from centers 1 and 2, while an external validation cohort comprising 106 patients was sourced from center 3. Preoperative computed tomography (CT) images were segmented to extract radiomics features, and a radiomics score (radscore) was calculated through feature engineering. In addition, intratumor heterogeneity (ITH) scores were derived by integrating clustered mask regions with global pixel distribution patterns. To predict DFS, five time-to-event ML models were trained: Cox proportional hazards, FastKernelSurvivalSVM, GradientBoostingSurvival (GB-Survival), RandomSurvivalForest, and ExtraSurvivalTrees. Model performance was assessed using the concordance index (C-index), and Survival SHapley Additive exPlanations over time (SurvSHAP (t)) analysis was conducted for model interpretation.

Results: Among the models tested, GB-Survival demonstrated the highest predictive performance for DFS, achieving a C-index of 0.7823. SurvSHAP (t) analysis revealed that the key prognostic factors included the ITH score, pathological TNM stage, lymphovascular invasion, radscore, and the prognostic nutritional index.

Conclusions: The GB-Survival model that integrates multimodal data outperforms other time-to-event ML models in predicting DFS for LACRC. This approach may facilitate the development of data-driven treatment strategies and personalized risk stratification for patients with LACRC.

Purpose: To compare the clinical presentation and timing of anastomotic leakage (AL) in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) versus conventional colorectal surgery (CCS), and to assess postoperative symptom trajectories to identify early indicators of AL. This study aims to improve timely recognition and facilitate earlier intervention of AL.

Patients and methods: We analyzed prospectively collected data from two Dutch teaching hospitals. We included adult patients who developed AL after elective CRS-HIPEC and CCS. We compared timing, severity, and clinical presentation of anastomotic leakage between patients after CRS-HIPEC and CCS. Furthermore, we analyzed and compared clinical symptoms, vital signs and laboratory values up to 5 days before AL diagnosis to evaluate symptom trajectories to identify early diagnostic indicators.

Results: Among 127 patients with anastomotic leakage, those who underwent CRS-HIPEC (n = 17) were diagnosed later (median 7 vs. 5 days, p < 0.001) and had longer hospital stays (median 24 vs. 16 days, p = 0.011). Except for a higher heart rate (mean 111 vs. 100 bpm, p = 0.02) and a steeper increase in the days preceding diagnosis in patients undergoing CRS-HIPEC, other symptoms and laboratory values were similar. Heart rate, temperature, and CRP began to increase in both groups the day before diagnosis.

Discussion: Anastomotic leakage was diagnosed later after CRS-HIPEC compared with CCS, with similar presentation, resulting in longer hospitalization. Symptoms began to increase the day before diagnosis. Future research should focus on developing a diagnostic algorithm based on dynamic postoperative trends to enable earlier intervention and improve outcomes.

Background: Increased application of neoadjuvant therapy (NAT) and adjuvant therapy (AT) could limit treatment options for pancreatic ductal adenocarcinoma (PDAC) recurrence. This study aimed to identify patterns of recurrence-focused treatment and survival following different primary treatment strategies.

Methods: All patients who underwent PDAC resection in the Netherlands (2014-2019) were included. Patients were divided into five groups according to their primary treatment strategy: (1) resection only, (2) gemcitabine-based NAT + resection, (3) FOLFIRINOX-based NAT + resection, (4) resection + gemcitabine-based AT, and (5) resection + FOLFIRINOX-based AT. Differences in recurrence-focused treatment and post-recurrence survival (PRS) were assessed using multivariable logistic and Cox-proportional hazards analyses and were presented as odds ratios (ORs) and hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs), respectively.

Results: In total, 1739 patients (median follow-up of 51 [interquartile range 34-64] months) were included, of whom 1272 (73%) had disease recurrence. In these patients, recurrence-focused treatment was administered in 64/124 (52%) after FOLFIRINOX-based NAT compared with 74/410 (18%) with resection only (OR 4.13 [95% CI 3.34-5.12]; P<0.001), 29/70 (41%) with gemcitabine-based NAT (OR 1.61 [95% CI 1.21-2.15]; P<0.001), 239/604 (39%) with gemcitabine-based AT (OR 1.73 [95% CI 1.43-2.09]; P<0.001), and 24/64 (38%) with FOLFIRINOX-based AT (OR 1.44 [95% CI 1.06-1.95]; P=0.02). Recurrence-focused treatment was associated with a median PRS of 11 (95% CI 10-13) months compared with 3 (95% CI 2-3) months in patients with best supportive care (HR 0.31 [95% CI 0.26-0.37]; P<0.001).

Conclusions: Recurrence-focused treatment differs between patients with PDAC who received different primary treatment strategies and is associated with improved PRS.