Search Results (8,976)

Despite advances in surgical technique and perioperative care, pancreatic ductal adenocarcinoma (PDAC) remains associated with poor survival. Sarcopenia is highly prevalent in PDAC and is consistently associated with inferior survival and reduced tolerance of systemic therapy. However, interventions primarily aimed at increasing muscle mass through nutritional supplementation and resistance-based exercise have yielded limited improvements in clinically meaningful postoperative outcomes. This has prompted increasing interest in sarcopenia as a marker of broader biological vulnerability rather than isolated physical deconditioning. Emerging clinical, translational, and experimental evidence demonstrates that skeletal muscle and adipose tissue function as active immunometabolic organs, and that cancer-associated inflammatory pathways drive early muscle loss, immune dysfunction, and impaired physiological recovery. Across multiple clinical cohorts, sarcopenia is reproducibly associated with worse overall survival and failure to complete adjuvant therapy, but not consistently with increased postoperative complications, suggesting that its prognostic relevance lies in impaired recovery and oncological fitness rather than immediate surgical risk. Translational studies further indicate that sarcopenia identifies patients with reduced antitumor immune competence, particularly in early-stage disease. This review synthesizes current evidence linking sarcopenia, immune dysfunction, and surgical outcomes in PDAC and examines implications for perioperative care. We propose that immunometabolic-informed prehabilitation, integrated with existing nutritional and exercise strategies, may represent a more effective approach to improving recovery, treatment tolerance, and durable oncological outcomes following PDAC resection. Full article

Mixed hepatocellular carcinoma (HCC)–neuroendocrine carcinoma (NEC) is a major type of liver mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN). Primary liver NEC, which is very rare, is mostly associated with HCC rather than pure NEC. To characterize the cancer cell heterogeneity of the HCC and NEC components, we comprehensively analyzed the protein expression of three cancer cell biological markers (TERT, Ki-67, and p53) and five differentiation markers (one hepatocyte marker and four neuroendocrine markers) via immunohistochemistry and immunofluorescence using curative resection tissues from three patients with liver MiNEN. TERT/Ki-67/p53 proteins, which are related to cell proliferation and malignancy, were independently expressed in the HCC and NEC components; Ki-67 was highly expressed among the three proteins in both cancer components, and the expression of all three markers was higher in the NEC component than in the HCC component. Despite the intracomponent and intercomponent heterogeneity, the expression signatures of the three markers were similar between the two components, potentially suggesting a common origin of mixed HCC-NEC. An in-depth exploration of intracomponent heterogeneity using differentiation markers revealed multiple intermediate phenotypes of cancer cells, i.e., HCC-like and NEC-like cells, mainly in the HCC component. Histologically NEC-like cells rather than HCC-like cells tended to have an intermediate percentage of Ki-67-positive cells, compared with NEC cells. The spatial distribution of various intermediate cancer cell phenotypes suggests that mixed HCC-NEC may involve the transdifferentiation from HCC cells to NEC cells through the dedifferentiation of HCC. Full article

Background: Esophageal schwannomas are extremely rare, benign mesenchymal tumors originating from the nerve sheath tissues of autonomic nerves, accounting for less than 2% of all esophageal tumors. This systematic review aims to provide a detailed analysis of esophageal schwannomas (ESs), focusing on tumor characteristics, diagnostic methods, and treatment options. Methods: A systematic search of English literature databases, including ScienceDirect, Springer, PubMed, and Google Scholar, was conducted up to 2023. The keywords used were ‘esophageal schwannoma,’ ‘gastrointestinal schwannoma,’ ‘esophageal neurinoma,’ and ‘esophageal neurilemoma.’ Studies were reviewed for patient demographics, clinical presentation, diagnostic methods, tumor characteristics, and management options. Results: A total of 370 articles met the inclusion criteria, with 80 articles (89 cases) included in the final analysis. The mean age of patients was 51.8 years, with a female predominance (73%). Most cases were reported from East Asia (60.7%). Most (71%) patients presented with dysphagia, and 12% were asymptomatic. Preoperative diagnosis often involved CT scans (75.28%), upper endoscopy (73.03%), and EUS (49.4%). Tumors averaged 77.86 mm in size as per CT, MRI and PET-CT, with the upper esophagus being the most common location (55.55%). Surgical resection was the primary treatment, with enucleation being the most frequent procedure (58.9%). The prognosis was generally excellent, with no reported recurrences during follow-up periods. Conclusions: Esophageal schwannomas are extremely rare. Surgical resection remains the treatment of choice, with a high success rate and excellent prognosis. Further studies are needed to standardize diagnostic and treatment protocols for these rare tumors. Full article

Background/Objectives: Pancreatic surgery has always been associated with a variety of complications. In the current study, we analyzed more than 800 consecutive pancreatic resections and tried to find clinically relevant routine parameters that could predict adverse outcomes at an early stage. We focused on hepato-pancreato-biliary routine parameters, especially on liver enzymes, because so far there are no studies showing any correlation between postoperatively elevated liver enzymes and postoperative complications. Methods: All pancreatic resections of a tertiary care center from 2003 until 2025 were documented prospectively and analyzed retrospectively. Data analysis comprised descriptive as well as inferential statistical analyses. Results: Laboratory values from 808 consecutive resections were analyzed for the first week after surgery. Elevated aspartate aminotransferase (AST) was associated with postoperative hemorrhage on POD 1, pulmonary insufficiency on POD 1 to 4, other complications on POD 1 to 5, MODS on POD 2 to 4, and development of pneumonia on POD 3 to 5. Elevated alanine aminotransferase (ALT) was associated with pulmonary insufficiency on POD 1 to 4 and POD 6, pneumonia, and other complications on POD 3. It was also associated with MODS on POD 1 to 6. Bilirubin elevated preoperatively and on POD 1 could not really predict any complication. In this study, we can also confirm that elevated amylase and lipase can predict complications. Conclusions: This is the first study that shows a correlation between postoperatively elevated AST and ALT and the development of postpancreatectomy complications. Elevated AST and ALT, especially in combination with postoperative pancreatitis or at least elevated pancreatic enzymes, can identify patients at risk for life-threatening conditions and might be useful to decrease failure-to-rescue patients. Full article

Background/Objectives: Total neoadjuvant therapy (TNT), integrating systemic chemotherapy and radiotherapy before surgery or surveillance, has become a standard approach for locally advanced rectal cancer (LARC). However, optimal sequencing strategies and long-term outcomes of watch-and-wait (W&W) following sandwich TNT remain insufficiently characterized. We evaluated oncologic outcomes and treatment response in patients treated with an institutional sandwich TNT protocol. Methods: We conducted a retrospective cohort study of consecutive patients with LARC treated with sandwich TNT (induction chemotherapy followed by hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost [IMRT-SIB] chemoradiotherapy and consolidation chemotherapy) at the Institute of Oncology Ljubljana between 2016 and 2023. The primary endpoint was an overall complete response (CR; pathological [pCR] and clinical [cCR]). Secondary endpoints included tumor regression grade (TRG), major pathological response (MPR), R0 resection rate, organ preservation, overall survival (OS), and disease-free survival (DFS). Results: Among 205 patients (median age 61 years), overall CR was 29.5% (pCR 19.3% and cCR 10.2%). Major pathological response (TRG 3–4) occurred in 37.6%. R0 resection was achieved in 94.5%. In the W&W cohort (n = 21), local regrowth occurred in 33.3% (95% CI, 14.6–57.0%) over a median follow-up of 4.96 years. Total mesorectal excision (TME)-free survival at 5 years was 73.1% (95% CI, 55.0–97.2%). Estimated 5-year OS was 81.1% (95% CI, 75.5–87.2%) and 5-year DFS was 75.2% (95% CI, 69.0–82.0). In multivariable analysis, non-R0 resection (HR 6.06, 95% CI, 1.99–18.42), MRI circumferential resection margin positivity (HR 3.11, 95% CI, 1.53–6.33), and MRI extramural vascular invasion positivity (HR 1.97, 95% CI, 1.05–3.91) remained independent predictors of DFS. Conclusions: Institutional sandwich TNT yields meaningful tumor response and durable survival in MRI-defined high-risk LARC. Structured W&W offers organ preservation with acceptable oncologic control under intensive surveillance. Full article

Background: Postoperative liver injury remains a major challenge after curative-intended liver resection for hepatocellular carcinoma (HCC), impacting both early complications and long-term survival. The recently introduced SAAR (Sum of AST/ALT Ratios) score may serve as a novel marker for predicting postoperative outcomes. Methods: This retrospective single-center study included 213 patients undergoing liver resection for HCC between January 2007 and October 2024. The SAAR score was calculated using AST/ALT ratios on postoperative days 1 and 3 and correlated with post-hepatectomy liver failure (PHLF), disease-free survival (DFS), and overall survival (OS). The predictive performance of the SAAR score was compared with that of the combined APRI + ALBI score. Results: Patients with SAAR ≥ 2 showed significantly higher rates of PHLF (OR = 2.5, p = 0.019) and impaired long-term outcomes. Median DFS and OS were significantly reduced in the SAAR ≥ 2 group (7 vs. 24 months, p < 0.001; 12 vs. 32 months, p = 0.004, respectively). Multivariate Cox regression confirmed SAAR ≥ 2 as an independent predictor for DFS (HR = 2.1) and OS (HR = 1.9). The APRI + ALBI score also demonstrated strong preoperative predictive value for PHLF (AUC = 0.854) but not for long-term outcome. Full article

Background/Objectives: Perioperative blood transfusion (BTF) remains controversial regarding its impact on oncological outcomes in colorectal cancer (CRC). This study aimed to evaluate the association between BTF, transfusion volume, and long-term prognosis in CRC patients undergoing radical resection. Methods: We conducted a retrospective cohort study of 1777 CRC patients who underwent radical surgery at the Fourth Hospital of Hebei Medical University between December 2007 and April 2015. Propensity score matching (PSM) was applied to minimize selection bias between BTF and non-BTF groups. Logistic regression identified factors associated with BTF receipt. Cox proportional hazards models assessed the association between BTF and 5-year overall survival (OS). X-tile analysis determined optimal cut-off values for transfusion volume stratification. Results: Among 1777 patients, 729 (41.02%) received BTF. After PSM, 524 well-matched pairs showed balanced baseline characteristics. Intestinal obstruction was independently associated with BTF requirement (p < 0.001). The BTF group demonstrated significantly inferior 1-, 3-, and 5-year OS compared with non-BTF groups in both overall and PSM cohorts (all p < 0.01). Multivariate Cox analysis identified BTF as an independent adverse prognostic factor (HR = 1.44, 95% CI 1.09–1.89, p = 0.01). X-tile analysis stratified patients into non-BTF, small-volume (≤4 units), and massive-volume (>4 units) groups. Massive-volume transfusion showed the poorest survival outcomes (p < 0.0001) and was independently associated with worse OS (HR = 1.61, 95% CI 1.18–2.20, p = 0.003). Supplementary analyses indicated that no independent association was observed between survival outcomes and either preoperative inflammatory markers or the specific timing and type of transfusion. Conclusions: BTF, particularly when exceeding 4 units, independently predicts inferior long-term survival in CRC patients following radical resection. These findings support the implementation of restrictive transfusion strategies in perioperative CRC management. Given its retrospective observational design, this study shows an association but does not establish causality, and our findings should be interpreted in light of the aforementioned limitations. Full article

Background/Objectives: Totally endoscopic mitral valve repair reduces surgical trauma and accelerates recovery but can be technically challenging, particularly for precise annuloplasty suturing. The VirtuoSEW^® (LSI Solutions, Victor, NY 14564m, USA) automated annular suturing system was developed to standardize and simplify suture placement. This study was an early evaluation of this technology’s safety, efficacy, and feasibility in totally endoscopic microInvasive mitral valve repair (µMVr). Methods: We conducted a retrospective observational study of 20 patients with severe mitral valve disease of various etiologies. All patients underwent mitral valve repair using the VirtuoSEW^® system for automated placement of annuloplasty sutures, combined with leaflet resection or chordal management as appropriate. Postoperative outcomes were assessed at one month using echocardiography and clinical evaluation. Perioperative and postoperative complications and early mortality were systematically recorded. Results: VirtuoSEW^®-assisted mitral valve repair was safe and effective, achieving complete elimination of severe mitral regurgitation in all patients (N = 20, 100%). Annuloplasty rings included Physio-ring (N = 12, 60%), Memo 3D (N = 4, 20%), and Memo 4D (N = 4, 20%), combined with leaflet repair techniques: leaflet plication (N = 5, 25%), neochordae implantation (N = 7, 35%), sliding plasty (N = 2, 10%), commissural repair (N = 1, 5%), and hemibutterfly repair (N = 1, 5%). Concomitant procedures included: tricuspid valve repair (N = 1, 5%) and atrial septal defect closure (N = 1, 5%). Mitral annulus diameter decreased from 42.0 ± 5.3 mm to 34.2 ± 2.2 mm (p = 0.001). Mean total surgery, cardiopulmonary bypass, and aortic cross-clamp times were 170.3 ± 21.3, 143.4 ± 21.5, and 80.4 ± 7.9 min, respectively. ICU stay was 1.0 ± 0.2 days, with a hospital stay of 8.0 ± 1.9 days. No perioperative complications—including bleeding (N = 0, 0%), stroke (N = 0, 0%), infections (N = 0, 0%), or 30-day mortality (N = 0, 0%)—occurred. Conclusions: µMVR invasive mitral valve repair using the VirtuoSEW^® system is safe, effective, and reproducible, as well as compatible with almost all repair techniques, providing complete restoration of valve competence with no early device-related complications. To our knowledge, this is the first clinical study reporting outcomes with this device, supporting its potential to streamline mitral repair and improve procedural efficiency. Full article

Background: National guidelines recommend adjuvant chemotherapy (AC) following resection for all stages of pancreatic cancer (PDAC), but the benefit of AC in Stage IA disease remains unclear. The objective of this study was to identify a subgroup of patients with Stage IA PDAC that could possibly forego AC. Study Design: The National Cancer Database (NCDB) was queried to identify all patients with Stage IA PDAC diagnosed from 2010 to 2021. Patients who received AC were compared to those who did not. Multivariable analysis was conducted to identify risk factors associated with overall survival (OS). Results: There were 1421 patients eligible for analysis. On multivariable analysis, we found nine factors associated with worse overall OS: advanced age (p = 0.0414), lower median income (p = 0.0148), Medicare (p = 0.0180), higher-grade tumor histology (p = 0.0182), LVI (p = 0.0028), positive surgical margins (p = 0.0027), examination of fewer than 12 lymph nodes (p = 0.0395), and a length of stay greater than 7 days (p < 0.0001). OS was negatively correlated with an increased number of risk factors. Improved OS was observed following AC in patients with three (∆OS = +54 months; p = 0.0016) or four or more risk factors (∆OS = +11.4 months; p = 0.0250). However, patients with fewer than three risk factors did not experience improvement in OS following AC. Conclusions: AC does not appear to benefit Stage IA PDAC patients with fewer than three risk factors indicating that it may be safe to omit AC in these individuals. Full article

Introduction: As multimodal therapy for esophageal cancer advances, addressing immediate and long-term functional outcomes following surgery has become more important. Despite surgical advancements, delayed gastric conduit emptying (DGCE) remains a primary cause of functional impairment after esophageal cancer resection. The literature addressing pylorus management following minimally invasive esophagectomy (MIE) is scarce. The effects of pyloric drainage with pyloromyotomy or postoperative approaches such as intrapyloric Botox injection or dilatation on the incidence and course of DGCE were the focus of this study. Methods: A retrospective analysis of consecutive patients after minimally invasive esophagectomy with thoracic esophagogastric anastomosis and gastric tube reconstruction between 2014 and 2023 was performed. Univariate analyses were used to identify significant patient-, tumor-, and procedure-related factors affecting DGCE. Results: A total of 276 patients were included. DGCE was observed in 80 (28.9%) patients. Demographics did not differ with statistical significance. Postoperative complications were not increased in patients with DGCE. Pyloric intervention (PI) did not reduce postoperative occurrence of DGCE (PI: n = 19/23.75% compared to no PI: n = 62 (30.5%), p = 0.342). Median length of hospital stay was significantly longer, and total costs were significantly higher in patients with DGCE (p = 0.03 and p = 0.047, respectively). Analysis of endoscopic approaches was not associated with a statistically significant difference between botulinum toxin injection and pyloric dilatation with regard to reinterventions. Conclusions: While DGCE is frequent after esophagectomy, it is not associated with short-term morbidity but with prolonged total hospital stay and increased costs. Intraoperative pyloric intervention does not influence the incidence of DGCE after esophagectomy and endoscopic management was associated with therapeutic success, but choice of specific, optimal approach remains elusive. Novel concepts, including preoperative dilatation should be investigated. Full article

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery has become the standard treatment for oesophageal cancer. However, data on the outcomes of neoadjuvant immunochemotherapy (nICT) in geriatric patients (≥70 years) who face higher perioperative risks are limited. Objective: This study aimed to compare the perioperative outcomes of nICT versus nCRT in elderly patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Method: This retrospective cohort study included 132 geriatric patients (median age: 72 years) treated with nICT (n = 51) or nCRT (n = 81) followed by esophagectomy at Sichuan Cancer Hospital (2021–2024). Intraoperative outcomes, postoperative pathologic stages, and complications, including pneumonia and anastomotic leakage, were assessed. Propensity score matching (PSM), overlap weighting (OW), and inverse probability of treatment weighting (IPTW) were used to adjust for baseline covariate imbalances in the sensitivity analysis. Results: Pathologic ypT0 stage tended to be higher in the nCRT group (p = 0.014), whereas ypN0 was higher in the nICT group (p = 0.035). No significant differences in intraoperative or postoperative outcomes between the two groups, except for pulmonary complications (p > 0.05). Compared with nCRT patients, nICT patients had significantly lower pulmonary complication rates (13.7% vs. 32.1%, p = 0.030), and multivariable analysis confirmed these findings (adjusted OR = 0.26; 95% CI: 0.08–0.85; p = 0.026). Sensitivity analyses showed consistent results. Conclusions: The safety of nICT is comparable to that of nCRT in geriatric ESCC patients, with significantly fewer pulmonary complications. These findings support nICT as a valuable alternative for elderly populations. Full article

The liver is the most common site of metastatic disease in patients with colorectal cancer. However, the multidisciplinary management of colorectal liver metastases (CLMs) remains suboptimal. Over the past several decades, numerous randomized trials have evaluated the efficacy of adjuvant chemotherapy following CLM resection, revealing improvements in disease-free survival. Nevertheless, these studies have not consistently demonstrated benefits in overall survival, resulting in controversy with regard to the role of routine postoperative chemotherapy. Circulating tumor DNA (ctDNA) has recently emerged as a promising biomarker for detecting molecular residual disease after surgery. Multiple studies have consistently shown that postoperative ctDNA positivity is strongly associated with inferior recurrence-free survival and overall survival in patients with colorectal cancer. In addition to its prognostic value, ctDNA may also assist in guiding postoperative therapeutic decisions. In prospective observational studies of CLM, adjuvant chemotherapy provided potential clinical benefits primarily in patients with ctDNA-positive disease, whereas limited benefits were observed in ctDNA-negative patients. These findings suggest that ctDNA-based detection of molecular residual disease may aid in developing a framework for risk-adapted postoperative management after CLM resection. However, several challenges remain, including the identification of an optimal treatment regimen for ctDNA-positive patients and the improvement of ctDNA assay sensitivity. Ongoing biomarker-driven clinical trials may clarify whether ctDNA-guided strategies can improve patient selection and clinical outcomes following curative resection of CLM. Full article

Background/Objectives: Intrapulmonary metastasis (IPM) after an initial single primary lung cancer (SPLC) is an adverse follow-up pattern; however, when studying population-based longitudinal records, the determinants remain unclear. We aimed to identify factors associated with subsequent IPM after initial SPLC using artificial intelligence (AI)-driven analytical approaches. Methods: We used Surveillance, Epidemiology, and End Results (SEER) lung cancer records from 2000 to 2019. Adults with at least two records were restricted to those with SPLC at the first record. Outcome at the second record was registry-classified IPM versus persistent SPLC. A machine learning framework based on random forest models was developed using baseline variables, first record characteristics, and the interval between records. Temporal validation was performed by training on cases from 2000 to 2013 and testing on cases from 2014 to 2019. A dynamic Bayesian network (DBN) supported simulated intervention (SI) analyses to estimate model-implied risk ratios (RRs) with 95% confidence intervals (CIs). Results: Among 3450 patients, 361 had registry-classified IPM at the second record. The random forest model achieved an area under the curve (AUC) of 0.852 in internal validation and 0.929 in temporal validation. Surgery and record timing were the leading predictors. The DBN retained surgery as the only direct parent and achieved an AUC of 0.779. SI analyses showed higher IPM probability for pleural invasion level (PL) 3 versus PL 0, RR 1.378 (95% CI, 1.080–1.657). Lobectomy with mediastinal lymph node dissection versus wedge resection lowered the IPM probability, RR 0.378 (95% CI, 0.219–0.636). Conclusions: AI-based time-sequence modeling integrating machine learning and a DBN allowed for the identification of surgery, pleural invasion, and record timing as key factors associated with subsequent IPM classification after initial SPLC. This framework demonstrates the potential of combining predictive and probabilistic dependency modeling to investigate registry-based disease classification patterns, and may support hypothesis generation for future prospective studies. Full article

Background: Glioblastoma remains the most aggressive and treatment-resistant primary brain tumor, with patient outcomes strongly associated with the extent of surgical resection. Tumor recurrence is largely driven by infiltrating glioma cells that extend beyond the contrast-enhancing margin, which has traditionally served as the boundary for surgical resection. Advances in pre- and intraoperative imaging, functional mapping, and fluorescence guidance have challenged the conventional definition of “maximal safe resection” and given rise to the concept of supramaximal resection (SMR). This technique, where surgical resection extends beyond the contrast-enhancing border, has garnered significant interest in recent years and shown promising preliminary survival outcomes. However, the lack of standardized definitions and methodological consistency has limited reproducibility and clinical adoption. Methods: A systematic literature search of PubMed/MEDLINE, Embase, and Web of Science was performed from database inception through March 2026 in accordance with PRISMA guidelines. Studies investigating resection beyond the contrast-enhancing tumor margin in adult glioblastoma patients were evaluated for inclusion. Results: A total of 1045 records were identified, with 37 studies meeting inclusion criteria. Across studies, SMR was frequently associated with improved progression-free and overall survival in selected patients, particularly following complete contrast-enhancing tumor resection. However, substantial heterogeneity exists in SMR definitions, and the current body of evidence is largely retrospective and derived from high-volume centers. Conclusions: SMR represents a promising extension of maximal safe resection targeting infiltrative tumor beyond conventional imaging boundaries. While emerging evidence suggests survival benefits, variability in methodology and patient-specific factors require cautious interpretation. Future standardization and prospective validation are needed to better define the role of SMR within multimodal glioblastoma treatment. Full article

Background/Objectives: Postoperative recurrence is a critical issue in the treatment of resectable pancreatic ductal adenocarcinoma (rPDAC). Moreover, the prognosis after early recurrence is extremely poor. This study aimed to develop a recurrence prediction model and to define early recurrence after upfront surgery (UFS) for rPDAC. Methods: This multicenter retrospective study included patients who underwent UFS for anatomically rPDAC between January 2013 and December 2017. Multivariate analyses were conducted to identify the risk factors for recurrence-free survival and to construct a recurrence prediction model. Subsequently, a minimum p value approach was used to determine the optimal cutoff values for early and late recurrence. Results: The cohort included 603 patients (325 men and 278 women). During the median follow-up period of 25 months (interquartile range, 15–38 months), 381 patients (63.2%) experienced a recurrence. Multivariate analyses revealed carbohydrate antigen 19-9 ≥37 U/mL (hazard ratio [HR], 1.58; p < 0.001), tumor size ≥ 2.2 cm (HR, 1.59; p < 0.001), lymph node metastasis (HR, 1.86; p < 0.001), R1 resection (HR, 1.56; p = 0.002), and no adjuvant chemotherapy (HR, 1.54; p < 0.001) as independent predictors. The recurrence prediction model demonstrated an area under the curve of 0.72–0.75. The optimal threshold for early and late recurrences was a recurrence-free interval of five months. Carbohydrate antigen 19-9 ≥ 156 U/mL was a significant predictor of early recurrence (OR, 3.28; p < 0.001). Conclusions: This study identified the prognostic risk factors for recurrence and developed a recurrence prediction model for patients undergoing UFS for rPDAC. Moreover, a recurrence-free interval of five months was identified as the optimal threshold for distinguishing between early and late recurrences. Full article