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18 pages, 4702 KB  
Article
Pilot Study of Partial Tumor Ablation Using Thermal High-Intensity Focused Ultrasound (HIFU) in Feline Soft Tissue Sarcomas
by Lauren Ruger, Ester Yang, Sheryl Coutermarsh-Ott, Marlie Nightengale, Andy Hsueh, Elliana R. Vickers, Brittany Ciepluch, Eli Vlaisavljevich, Nikolaos Dervisis and Shawna Klahn
Animals 2026, 16(10), 1530; https://doi.org/10.3390/ani16101530 (registering DOI) - 16 May 2026
Abstract
Soft tissue sarcomas (STS) are locally invasive and aggressive tumors that occur spontaneously in humans, dogs, and cats. High-intensity focused ultrasound (HIFU) is a non-invasive ablation technology that has been explored in canine but not feline STS. The objective of this pilot study [...] Read more.
Soft tissue sarcomas (STS) are locally invasive and aggressive tumors that occur spontaneously in humans, dogs, and cats. High-intensity focused ultrasound (HIFU) is a non-invasive ablation technology that has been explored in canine but not feline STS. The objective of this pilot study was to determine the in vivo safety and feasibility of HIFU ablation for feline STS and to investigate the impact of HIFU on the acute immunological response. Client-owned cats diagnosed with spontaneous STS were recruited. Computed tomography (CT) scans of the chest, abdomen, and tumor were performed prior to treatment for staging and treatment planning. A commercially available HIFU unit (Echopulse, Theraclion, Malakoff, France) was used to target portions of solid tumors before standard-of-care surgical resection. Ablation efficacy and local immunological response were characterized using histopathological and immunohistochemical assessments. Acute safety was monitored with physical examinations, owner reports, and CBC/serum biochemistry. Multiplex serum cytokine levels were used to evaluate the systemic immune response. A total of three cats diagnosed with STS were recruited and treated. No significant adverse events attributed to HIFU treatment were noted in this pilot study. In treated areas, hemorrhage as well as coagulative and lytic necrosis were observed microscopically and were more extensive than in untreated tissues. There was a statistically significant difference in the level of serum MCP-1 after HIFU treatment, but no significant changes in any other analytes. No differences in the infiltration of CD3-, CD79a-, or IBA1-positive cells were noted between treated and untreated samples. Overall, findings suggested that HIFU may offer a viable alternative to conventional therapies for feline STS, with pilot results showing effective tumor ablation in cats with STS without significant adverse events. Some preliminary evidence of immunomodulation following treatment was observed, but HIFU as an immunotherapeutic treatment option needs to be further investigated. Full article
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19 pages, 1376 KB  
Review
Systems Biology and Multi-Omics Determinants of Response to Bladder-Preserving Trimodality Therapy in Muscle-Invasive Bladder Cancer
by Vlad-Horia Schițcu, Vlad Cristian Munteanu, Mihnea Bogdan Borz, Ion Cojocaru, Octavia Morari, Mircea Gîrbovan and Andrei-Ionuț Tișe
Life 2026, 16(5), 826; https://doi.org/10.3390/life16050826 (registering DOI) - 16 May 2026
Abstract
Trimodality therapy (TMT)—maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy—can offer oncologic outcomes comparable to radical cystectomy (RC) in carefully selected muscle-invasive bladder cancer (MIBC) patients while preserving the bladder and, possibly, the quality of life. Systematic reviews and long-term [...] Read more.
Trimodality therapy (TMT)—maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy—can offer oncologic outcomes comparable to radical cystectomy (RC) in carefully selected muscle-invasive bladder cancer (MIBC) patients while preserving the bladder and, possibly, the quality of life. Systematic reviews and long-term series support durable bladder-intact survival in responders, yet there is still a significant percentage of patients who exhibit incomplete response or invasive intravesical recurrence requiring salvage RC. This review covers computational genomics, transcriptomics, immune contexture, radiogenomics, and digital pathology approaches for predicting response in order to avoid preventable TMT failures. We discuss clinically relevant endpoints (complete response, invasive recurrence, bladder-intact survival, and salvage RC), patient selection (carcinoma in situ, hydronephrosis, debulking feasibility, and histology), and DNA damage response (DDR) biology—highlighting ERCC2 and related pathways as determinants of chemo-radiation sensitivity. We then review reproducible transcriptomic subtype classifiers and immune deconvolution methods, emphasizing translational constraints and reporting standards. Finally, we propose an integrated hypothetical modeling framework (calibration, external validation, and decision-curve thresholds) to guide recommendations for upfront RC versus bladder preservation with intensified surveillance and timely salvage RC. Full article
(This article belongs to the Section Medical Research)
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15 pages, 1074 KB  
Article
Risk Factors and Nonlinear Risk Patterns of Prolonged Air Leak After Robot-Assisted Lung Resection for Lung Cancer: A Retrospective Cohort Study
by Hao Xu, Han Zhang and Linyou Zhang
Cancers 2026, 18(10), 1612; https://doi.org/10.3390/cancers18101612 - 15 May 2026
Abstract
Background/Objectives: Prolonged air leak (PAL) remains a common complication after lung resection and may delay postoperative recovery and subsequent treatment. This study aimed to identify clinical factors associated with PAL after robot-assisted thoracic surgery (RATS) and to explore potential nonlinear relationships using restricted [...] Read more.
Background/Objectives: Prolonged air leak (PAL) remains a common complication after lung resection and may delay postoperative recovery and subsequent treatment. This study aimed to identify clinical factors associated with PAL after robot-assisted thoracic surgery (RATS) and to explore potential nonlinear relationships using restricted cubic spline (RCS) modeling. Methods: A retrospective cohort of 1185 patients who underwent RATS for primary lung cancer was analyzed. Multivariable Firth logistic regression was used to identify independent predictors of PAL (≥5 days). A nomogram was constructed based on the final model and internally validated using 1000 bootstrap resamples; its clinical utility was assessed using decision curve analysis. RCS analysis was performed to evaluate potential nonlinear associations. Results: A total of 98 patients (8.3%) developed PAL. Male sex was independently associated with increased PAL risk (OR 3.29, p < 0.001), whereas higher FEV1 was associated with reduced risk (OR 0.50 per 1-L increase, p < 0.001). BMI showed a modest protective effect (OR 0.91, p = 0.01). Age was not significant in the linear model (p = 0.86), but RCS analysis demonstrated a significant nonlinear association, with increased risk at older ages. The nomogram demonstrated moderate discrimination (apparent C-statistic 0.670, optimism-corrected 0.644) and good calibration, with decision curve analysis confirming net clinical benefit over treat-all and treat-none strategies. Conclusions: Male sex and impaired pulmonary function are key predictors of PAL after RATS. Nonlinear modeling revealed complex age-related risk patterns not captured by conventional approaches. The proposed nomogram may assist in preoperative risk stratification and perioperative decision-making. Full article
(This article belongs to the Special Issue Advances in Minimally Invasive Surgery in Thoracic Oncology)
11 pages, 450 KB  
Article
Comparative Neurocognitive Outcomes Following Holmium Laser Enucleation and Transurethral Resection of the Prostate: A Prospective Cohort Study
by Orkunt Özkaptan, Cengiz Çanakcı, Erdinç Dinçer, Osman Murat İpek, Mehmet Burak Doğrusever, Oğuz Türkyılmaz, Alper Coşkun and Sare Dilek Özkaptan
Medicina 2026, 62(5), 971; https://doi.org/10.3390/medicina62050971 (registering DOI) - 15 May 2026
Abstract
Background and Objectives: To evaluate the impact of Holmium Laser Enucleation of the Prostate (HoLEP) versus Transurethral Resection of the Prostate (TURP) on cognitive function and psychological well-being three months post-surgery. Materials and Methods: This prospective observational cohort study involved 150 [...] Read more.
Background and Objectives: To evaluate the impact of Holmium Laser Enucleation of the Prostate (HoLEP) versus Transurethral Resection of the Prostate (TURP) on cognitive function and psychological well-being three months post-surgery. Materials and Methods: This prospective observational cohort study involved 150 patients undergoing surgical treatment for BPH; 132 patients (66 HoLEP, 66 TURP) completed baseline and 3-month follow-up evaluations. The Montreal Cognitive Assessment (MoCA) served as the primary measure of cognitive function, while the Mini-Mental State Examination (MMSE) functioned as a secondary measure. The Beck Anxiety Inventory and Beck Depression Inventory were utilized to assess individuals’ mental states. We employed repeated-measures General Linear Models, adjusted for age and educational attainment, to examine temporal variations. Results: Baseline demographic, clinical, cognitive, and psychological characteristics were comparable among the groups. The modified analysis revealed no significant interaction between time and surgical procedure for MoCA (p = 0.405), indicating that both groups exhibited comparable cognitive trajectories. No significant differences were seen between the groups in the adjusted MoCA scores (p = 0.162). A minor, statistically insignificant temporal effect was observed (p = 0.058; partial η2 = 0.028). Educational attainment independently forecasted cognitive performance (p = 0.024). The MMSE demonstrated a slight temporal effect (p = 0.015) with no interaction of approaches. Anxiety and depressive symptoms persisted uniformly and comparably among the groups. Conclusions: Three months post-surgery, neither HoLEP nor TURP was associated with a notable deterioration in cognitive performance. The surgical modality did not independently influence cognitive trajectory after adjusting for demographic variables. Contemporary endoscopic BPH surgery appears to be neurocognitively safe during the medium-term postoperative period. Full article
(This article belongs to the Section Urology & Nephrology)
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11 pages, 601 KB  
Article
The Prognostic Significance of the Second Predominant Histological Pattern in Resected Early-Stage Lung Adenocarcinoma: A Retrospective Cohort Analysis
by Marco Ghisalberti, Alberto Salvicchi, Angela Galgano, Rossella Reale, Chiara Catelli, Luca Luzzi and Piero Paladini
J. Clin. Med. 2026, 15(10), 3815; https://doi.org/10.3390/jcm15103815 - 15 May 2026
Abstract
Background: Lung adenocarcinoma is morphologically heterogeneous, composed of various histological patterns. The International Association for the Study of Lung Cancer (IASLC) grading system, based on the predominant pattern and the presence of high-grade components, underscores this heterogeneity’s prognostic relevance. However, the specific impact [...] Read more.
Background: Lung adenocarcinoma is morphologically heterogeneous, composed of various histological patterns. The International Association for the Study of Lung Cancer (IASLC) grading system, based on the predominant pattern and the presence of high-grade components, underscores this heterogeneity’s prognostic relevance. However, the specific impact of the non-predominant “second component” on survival outcomes in early-stage disease remains inadequately characterized. Methods: We conducted a retrospective, single-center study including 95 patients with pathological stage 0, I, and II (TNM 8th edition) lung adenocarcinoma who underwent complete anatomical resection (lobectomy or segmentectomy) between January 2020 and December 2021. Histopathological evaluation followed the WHO 5th edition classification, with patterns quantified in 5% increments. The second predominant component was defined as the second most represented histological pattern, irrespective of a fixed percentage threshold. Overall survival (OS) and disease-free survival (DFS) were analyzed. Results: A second predominant component was identified in 55 patients (57.9%). The most common second components were lepidic (30.5%), solid (18.9%), and micropapillary (10.5%). With a median follow-up of 36 months, the presence of a lepidic second component was an independent factor for improved OS (Hazard Ratio [HR] 0.70, 95% CI 0.52–0.95, p = 0.022) and DFS (HR 0.62, 95% CI 0.41–0.93, p = 0.021). Conversely, a micropapillary second component was a strong independent predictor of worse OS (HR 1.81, 95% CI 1.24–2.64, p = 0.002) and DFS (HR 2.03, 95% CI 1.32–3.12, p = 0.001). The solid second component showed an intermediate adverse effect on DFS (HR 1.45, 95% CI 1.01–2.08, p = 0.043). Conclusions: The second predominant histological pattern provides additional prognostic information beyond the IASLC grading system and may improve postoperative risk stratification in early-stage lung adenocarcinoma. A lepidic second component portends a favorable prognosis, while micropapillary and solid components denote aggressive tumor biology and higher recurrence risk. Incorporating the evaluation of second components into routine pathological reporting and clinical decision-making could enhance postoperative risk stratification and personalize adjuvant therapy strategies. Full article
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13 pages, 1273 KB  
Article
From Bailout to Benchmark? Rethinking the Alfieri Procedure for Mitral Regurgitation in Barlow’s Disease
by Karin Steiner, Bernhard Voss, Miriam Lang, Nikoleta Bozini, Spyridon Soulis, Martin Bichler, Maximilian-Niklas Bonk, Stephanie Voss, Keti Vitanova, Markus Krane and Konstantinos Sideris
J. Clin. Med. 2026, 15(10), 3818; https://doi.org/10.3390/jcm15103818 - 15 May 2026
Abstract
Background: Mitral regurgitation due to Barlow’s disease remains surgically demanding. Despite widespread experience, consensus is lacking on whether the Alfieri repair can serve as a deliberate and durable rather than a rescue strategy in this complex pathology. Methods: We retrospectively analyzed patients [...] Read more.
Background: Mitral regurgitation due to Barlow’s disease remains surgically demanding. Despite widespread experience, consensus is lacking on whether the Alfieri repair can serve as a deliberate and durable rather than a rescue strategy in this complex pathology. Methods: We retrospectively analyzed patients undergoing mitral valve repair due to severe mitral regurgitation resulting from Barlow’s disease using either the Alfieri or Neochordae repair techniques. Patients received a uniform semi–rigid annuloplasty ring, while leaflet resection and concomitant coronary or aortic procedures were excluded. Results: Baseline demographics and echocardiography were broadly comparable. Perioperative mortality was 0% in both cohorts, with similarly low rates of major complications. Aortic cross–clamp time was significantly shorter with Alfieri repair (p < 0.001). No relevant postoperative transmitral gradient or systolic anterior motion occurred. At a mean follow–up of 4.2 years, more–than–moderate MR was observed in one patient per group (Alfieri 2.4% vs. Neochordae 1.2%). At 10 years, the cumulative incidence of more–than–moderate mitral regurgitation and redo mitral surgery was similarly low between techniques (p = 0.810 and p = 0.460). Most patients were NYHA class I–II at last follow–up, demonstrating improved functional status. Echocardiography showed left ventricular reverse remodeling without intergroup differences. Conclusions: These data indicate that the Alfieri approach provides durable competence and hemodynamic safety comparable to the Neochordae technique while reducing cross–clamp time, supporting its use as a deliberate strategy rather than a bailout in anatomically suitable valves. Full article
(This article belongs to the Special Issue Clinical Therapeutic Advances of Mitral Regurgitation)
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15 pages, 4600 KB  
Case Report
Challenging a Benign, Elusive Tumor: Atypical Spinal Osteoblastomas in the Thoracic Spine with Surgical Resection and Hemi-Vertebral Body Reconstruction via a Posterior Approach—A Two-Case Series
by Joe Mehanna, Steffen-Heinrich Schulz, Sascha Gravius, Franz-Joseph Dally and Frederic Bludau
Reports 2026, 9(2), 152; https://doi.org/10.3390/reports9020152 - 15 May 2026
Abstract
Background and Clinical Significance: Osteoblastomas are rare, benign but locally aggressive bone tumors with a predilection for the posterior elements of the spine. Their clinical, radiological and histopathological presentation often overlaps with that of osteoid osteomas, leading to diagnostic and therapeutic challenges—particularly in [...] Read more.
Background and Clinical Significance: Osteoblastomas are rare, benign but locally aggressive bone tumors with a predilection for the posterior elements of the spine. Their clinical, radiological and histopathological presentation often overlaps with that of osteoid osteomas, leading to diagnostic and therapeutic challenges—particularly in atypical locations such as the anterior thoracic spine. Case Presentation: We report two cases of young female patients (aged 35 and 30 years) presenting with persistent thoracic back pain unresponsive to NSAIDs. In the first case, imaging revealed a lesion at the right T7 pedicle initially attributed to osteoid osteoma; CT-guided thermoablation was declined due to proximity to neural structures. At this stage, we chose percutaneous transpedicular ablation by drilling through the centrum of the lesion (Nidus) surgically. After this transpedicular resection with initial symptom improvement, the patient developed recurrence with lesion progression into both anterior and posterior columns, requiring a second, open, surgical intervention. In the second case, a lesion at the left T11 pedicle and transverse process was identified directly as osteoblastoma due to size and radiological morphology; initial biopsy was non-diagnostic due to specimen fragmentation. In both cases, histopathology was inconclusive or misleading, while clinical and radiological features—including NSAID unresponsiveness, lesion size, and anatomical extent—favored osteoblastoma. Both patients underwent surgical resection via posterior costotransversectomy, partial hemivertebrectomy, expandable cage placement, and posterior instrumentation (T5–T8 and T10–T12, respectively). The postoperative courses were complicated by thoracic events—hemothorax in the first case and pulmonary embolism in the second—both of which were managed successfully. At follow-up, both patients were neurologically intact and pain-free. Conclusions: These cases emphasize the diagnostic overlap between osteoid osteoma and osteoblastoma and highlight the importance of clinical and radiographic correlation when histopathology is inconclusive. A posterior-only approach with costotransversectomy may be a valid strategy in selected cases of thoracic spinal tumors, although specific complications such as hemothorax must be considered. Full article
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15 pages, 1063 KB  
Article
Blood Pressure Changes After Oral 5-Aminolevulinic Acid Hydrochloride Administered 4–8 h Before TURBT: An Additional Analysis of a Phase III Study (SPP2C102)
by Hideo Fukuhara, Makito Miyake, Keita Kobayashi, Atsushi Ikeda, Kent Kanao, Yoshinobu Komai, Ryo Fujiwara, Yusuke Sato, Rikiya Taoka, Keiji Inoue, Kiyohide Fujimoto and Mototsugu Oya
Life 2026, 16(5), 819; https://doi.org/10.3390/life16050819 (registering DOI) - 15 May 2026
Abstract
This study evaluated changes in blood pressure and hypotension-related adverse drug reactions (ADRs) following oral administration of 5-aminolevulinic acid hydrochloride (5-ALA) in patients undergoing transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis under blue light has demonstrated superior sensitivity compared with that of [...] Read more.
This study evaluated changes in blood pressure and hypotension-related adverse drug reactions (ADRs) following oral administration of 5-aminolevulinic acid hydrochloride (5-ALA) in patients undergoing transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis under blue light has demonstrated superior sensitivity compared with that of white light when 5-ALA is administered 4 to 8 h before TURBT (95.3% vs. 61.1%, p < 0.001); however, data regarding associated blood pressure change remain limited. In this study, blood pressure changes were monitored for 24 h after 5-ALA administration (20 mg/kg) and hypotension-related ADRs were assessed within 14 days post-dose. Both systolic and diastolic blood pressures reached their nadir at 2 h after 5-ALA administration. Absolute blood pressure values were lower in patients with ADRs, whereas the magnitude of blood pressure changes was not different between patients with and without ADRs. The incidence of hypotension, defined as systolic blood pressure ≤ 80 mmHg, was 2.1%, which was lower than that reported in previous retrospective studies (40.0–75.6%). Although hypotension-related ADRs occurred in 25.5% of patients, all events were non-serious and resolved without clinical sequelae. The lower incidence may partly reflect the exclusion criteria and medication restrictions applied in this protocol-controlled trial. Full article
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10 pages, 1192 KB  
Article
Objective Auricular Measurements and Patient Satisfaction Following Cartilage-Cutting Otoplasty Using Fascioperichondrial Flaps
by Timea Madaras, Mara Bărăbancia-Romete, Ruxandra Bodog, Horațiu-Paul Domnariu, Klara Brânzaniuc, Leonard Azamfirei, Bogdan-Andrei Suciu and Cristian Trâmbițaș
J. Clin. Med. 2026, 15(10), 3795; https://doi.org/10.3390/jcm15103795 - 14 May 2026
Abstract
Background/Objectives: Prominent ears, affecting approximately 5% of the population, can cause significant psychosocial distress without functional impairment. Methods: This retrospective single-center study evaluated a cartilage-cutting otoplasty technique augmented by three triangular fascioperichondrial flaps in 40 patients (80 ears), aged 6–37 years [...] Read more.
Background/Objectives: Prominent ears, affecting approximately 5% of the population, can cause significant psychosocial distress without functional impairment. Methods: This retrospective single-center study evaluated a cartilage-cutting otoplasty technique augmented by three triangular fascioperichondrial flaps in 40 patients (80 ears), aged 6–37 years (mean age: 13 years), treated between 2022 and 2024 at Târgu Mureș County Emergency Hospital. Results: Preoperative helical–mastoid distances (HMD) were elevated, superior: 21 mm, middle: 22 mm, inferior: 21 mm; concho-mastoid angle (CMA) averaged ~50°. Surgery involved postauricular skin excision, selective conchal cartilage resection, and flap fixation to the mastoid periosteum for stabilization. Measurements at immediate postoperative and 6-week follow-up showed significant reductions: superior HMD by 10 mm (immediate) and 9 mm (6 weeks), middle by 9 mm and 8 mm, inferior by 4 mm and 4 mm, CMA by 27° and 26° (all p < 0.001). Stability between postoperative and 6-week intervals was confirmed by ANOVA (no significant differences). Patient satisfaction was excellent: 75% very satisfied and 22% satisfied (97% overall positive), with no correlation with age or sex. Conclusions: This hybrid approach offers reliable correction, natural contours, and low postoperative complications, representing a feasible option in otoplasty. Longer-term prospective trials are recommended. Full article
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20 pages, 807 KB  
Article
Quality Without Compromise: A Propensity Score-Matched Analysis of Robotic Versus Laparoscopic Surgery for Locally Advanced Colorectal Cancer
by Marcin Kubiak, Wojciech Górski, Radosław Mlak, Zuzanna Dąbrowska, Jolanta Sado, Kinga Bielarska, Szymon Bielecki, Karol Rawicz-Pruszyński and Katarzyna Sędłak
Cancers 2026, 18(10), 1601; https://doi.org/10.3390/cancers18101601 - 14 May 2026
Abstract
Background: Minimally invasive surgery is the standard approach in colorectal cancer (CRC), yet the clinical value of robotic-assisted surgery (RAS) compared with laparoscopy remains under debate. This study aimed to compare surgical quality using textbook outcome (TO) and textbook oncological outcome (TOO) in [...] Read more.
Background: Minimally invasive surgery is the standard approach in colorectal cancer (CRC), yet the clinical value of robotic-assisted surgery (RAS) compared with laparoscopy remains under debate. This study aimed to compare surgical quality using textbook outcome (TO) and textbook oncological outcome (TOO) in patients undergoing minimally invasive resection for locally advanced CRC. Methods: A retrospective analysis of patients with locally advanced CRC (cT2-4N0-2M0) treated in a high-volume centre was performed. Patients undergoing laparoscopic or robotic surgery were included. Propensity score matching (PSM) was applied to balance baseline characteristics. TO was defined as an optimal perioperative course without complications, conversion, reintervention, prolonged length of stay, or mortality. TOO extended TO by including oncological parameters such as R0 resection and adequate lymph node yield. Results: A total of 123 patients were included (80 laparoscopic, 43 robotic), with 80 patients analyzed after PSM (40 per group). RAS was associated with significantly higher rates of intracorporeal (97% vs. 18.9%) and mechanical anastomoses (96.9% vs. 48.6%). No differences were observed in postoperative complications, reintervention rates, length of stay, or mortality. Although the comprehensive complication index was lower in the robotic group, this did not translate into improved TO or TOO rates. After matching, TO was achieved in 72.5% of RAS and 85.0% of laparoscopic cases (p = 0.1745), while TOO rates were also comparable between groups. No independent predictors of TO or TOO were identified in multivariable analysis. Conclusions: Robotic surgery for locally advanced CRC provides comparable perioperative safety and oncological quality to laparoscopy. The implementation of RAS in a high-volume centre does not compromise short-term outcomes, supporting its safe integration into clinical practice. Full article
(This article belongs to the Special Issue Laparoscopic and Robotic Surgery in Gastrointestinal Cancers)
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9 pages, 1976 KB  
Article
The Efficacy of Contrast-Enhanced Endoscopic Ultrasound for Differentiating Mural Nodules from Mucus Clots in Branch Duct IPMN
by Naoki Mita, Takuji Iwashita, Yuki Utakata, Takuya Koizumi, Yosuke Ohashi, Shota Iwata, Hironao Ichikawa, Kensaku Yoshida, Akinori Maruta, Shinya Uemura, Katsuhisa Toda, Nami Asano, Masaki Katayama, Tatsuhiko Miyazaki and Masahito Shimizu
Diagnostics 2026, 16(10), 1497; https://doi.org/10.3390/diagnostics16101497 - 14 May 2026
Abstract
Background/Objectives: The presence of a mural nodule (MN) is one of the findings indicating malignant transformation of an intraductal papillary mucinous neoplasm (IPMN). It is difficult to distinguish true MNs from mucus clots (MCs) by endoscopic ultrasound (EUS) alone. This study aimed [...] Read more.
Background/Objectives: The presence of a mural nodule (MN) is one of the findings indicating malignant transformation of an intraductal papillary mucinous neoplasm (IPMN). It is difficult to distinguish true MNs from mucus clots (MCs) by endoscopic ultrasound (EUS) alone. This study aimed to evaluate the efficacy of contrast-enhanced (CE)-EUS for differentiating true MNs from MCs and carcinoma from adenoma. Methods: A total of 104 patients who were diagnosed as having branch duct-type IPMNs with MN-like structures by EUS and underwent CE-EUS between January 2016 and August 2022 were included. MN-like structures without perfusion on CE-EUS were defined as MCs and those with perfusion were defined as true MNs. This was a retrospective study with limited pathological confirmation, and diagnoses in non-surgical cases were based on imaging and follow-up. Results: CE-EUS showed MN-like structures with perfusion in 35 patients and without perfusion in 69 patients. Surgical resection was eventually performed in a total of 28 patients and the diagnostic sensitivity, specificity and accuracy of MNs among them were 100%, 66.7% and 96.4% in CE-EUS; 48%, 66.7% and 50% in CE-CT; and 61.9%, 33.3% and 58.3% in MRCP, respectively. Possible risk factors indicating malignancy were statistically evaluated and presence of an MN was the only significant factor. Among the 35 true MNs, the height of an MN in carcinoma was significantly higher than that of an adenoma. The ROC analysis for detecting carcinoma in true MNs showed an area under the curve of 0.92 with the optimal cut-off value of 7 mm. When this cut-off value was used for diagnosing carcinoma, the sensitivity, specificity, and accuracy were 94.1%, 83.3% and 88.6%, respectively. Conclusions: CE-EUS may be useful for differentiating true MNs from MCs, although diagnostic performance should be interpreted cautiously because most non-surgical cases lacked pathological confirmation. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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17 pages, 1739 KB  
Article
Total Neoadjuvant Approach for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma—UK Tertiary Cancer Centre Experience
by Kai Tai Derek Yeung, Simon Gomberg, William Hodgson, Petula Jefferies, David Cunningham, Sheela Rao, Ian Chau, Naureen Starling, Charlotte Fribbens, Avani Athauda, Diana Tait, Irene Chong, Arabella Hunt, Magnus T. Dillon, Sacheen Kumar, Long R. Jiao, Ricky H. Bhogal and Katharine Aitken
Cancers 2026, 18(10), 1597; https://doi.org/10.3390/cancers18101597 - 14 May 2026
Abstract
Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related mortality. Radiological distinctions between borderline resectable (BR) and locally advanced disease (LA) are increasingly recognised as imperfect when considered without dynamic assessment. Neoadjuvant therapy (NAT) improves outcomes through tumour downstaging and early [...] Read more.
Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related mortality. Radiological distinctions between borderline resectable (BR) and locally advanced disease (LA) are increasingly recognised as imperfect when considered without dynamic assessment. Neoadjuvant therapy (NAT) improves outcomes through tumour downstaging and early treatment of occult metastatic disease, but the optimal NAT strategy, particularly in BR disease, remains uncertain. Published data evaluating combined systemic anti-cancer therapies (SACT) with or without chemoradiation (CRT) are limited and heterogeneous. Methods: This is a single-centre retrospective analysis of 44 patients with BR PDAC and a comparator cohort of 121 patients with LA PDAC treated with a total neoadjuvant approach of SACT with or without CRT and surgical resection between June 2017 and September 2022. Results: Median overall survival (OS) did not differ significantly between BR and LA disease (18 vs. 16 months, p = 0.14). Following NAT, 47.7% of BR and 18.1% of LA patients were anatomically suitable for surgical resection. Among unresected BR and LA patients, those treated with CRT in addition to SACT had a median OS of 18 and 21 months respectively. In the resected subgroup, resection margin status was the primary factor associated with survival; with R0 resection conferring a substantial OS advantage over R1, irrespective of initial BR/LA classification as diagnosis (47 vs. 22 months, p < 0.001). Conclusions: Despite anatomical differences at diagnosis, BR and LA PDAC demonstrated comparable survival outcomes when treated with total neoadjuvant strategies in this cohort. These findings challenge traditional radiological staging-based treatment paradigms and confirm that a margin-negative surgical resection offered the greatest opportunity for long-term survival for BR/LA PDAC patients. Full article
(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)
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20 pages, 5380 KB  
Article
Early Recurrence of HCC Is Driven by Inflammation-Related HIF-1α Independent Angiogenesis Rather than Hypoxia-Induced Immune Escape
by Lianda Siregar, Rino Alvani Gani, Toar J. M. Lalisang, Irsan Hasan, Suhendro, Heriawan Soejono, Siti Boedina Kresno, Nurjati Chairani Siregar and Muhammad Begawan Bestari
Biomolecules 2026, 16(5), 723; https://doi.org/10.3390/biom16050723 (registering DOI) - 14 May 2026
Abstract
Background: Hepatocellular carcinoma (HCC) shows a high rate of early recurrence after curative resection, indicating a critical contribution of tumor microenvironment-driven molecular mechanisms. Early recurrence of hepatocellular carcinoma is defined as recurrence within 6 months after curative resection, with a prevalence exceeding 30%. [...] Read more.
Background: Hepatocellular carcinoma (HCC) shows a high rate of early recurrence after curative resection, indicating a critical contribution of tumor microenvironment-driven molecular mechanisms. Early recurrence of hepatocellular carcinoma is defined as recurrence within 6 months after curative resection, with a prevalence exceeding 30%. Hypoxia signaling and immune dysregulation have been implicated, yet their compartment-specific relevance remains unclear. Methods: This multicenter nested case–control study included 49 HCC patients to evaluate associations between hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), tumor-infiltrating lymphocytes (TILs), CD4+ T cells, CD8+ T cells, regulatory T cells (Tregs), programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1) and early recurrence after resection. TIL density was assessed using hematoxylin and eosin staining, while immunohistochemistry was performed to quantify intratumoral and peritumoral expression of the studied markers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance. Recurrence-free survival (RFS) was analyzed using the Kaplan–Meier, and independent predictors were identified using multivariate Cox proportional hazards regression. Results: Early recurrence occurred in 11 of 49 patients (22.4%) of Child–Pugh A patients. Recurrent tumors were characterized by elevated VEGF expression despite absent HIF-1α, alongside significant depletion of intratumoral TILs (HR 5.02; 95% CI 1.09–23.26), CD4+ (HR 7.68; 95% CI 1.66–35.60) and CD8+ cells (HR 6.68; 95% CI 1.77–25.23) and reduced peritumoral CD8+ infiltration (HR 4.20; 95% CI 1.11–15.91). Multivariable analysis identified low intratumoral CD4+ (HR 7.98; 95% CI 1.63–39.07) and reduced peritumoral CD8+ expression (HR 4.98; 95% CI 1.14–21.70) as independent predictors, whereas HIF-1α, VEGF, Treg, PD-1, and PD-L1 were not significantly associated. Conclusions: Early HCC recurrence shows HIF-1α-independent angiogenesis alongside spatial immune depletion, supporting integrated immune profiling over single angiogenic markers. Full article
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51 pages, 996 KB  
Systematic Review
Neoadjuvant Treatment for Penile Cancer: A Systematic Review of Contemporary Evidence
by Jordan Santucci, Daniel Crisafi, Niranjan Sathianathen, Renu Eapen, Damien Bolton, Declan Murphy, Nathan Lawrentschuk and Marlon Perera
Cancers 2026, 18(10), 1595; https://doi.org/10.3390/cancers18101595 - 14 May 2026
Abstract
Background/Objectives: Penile squamous cell carcinoma (SCC) is a rare but aggressive malignancy in which survival declines sharply once regional lymph nodes are involved. Neoadjuvant therapy is recommended for clinically node-positive disease to improve resectability and address micro-metastatic spread; however, the supporting evidence [...] Read more.
Background/Objectives: Penile squamous cell carcinoma (SCC) is a rare but aggressive malignancy in which survival declines sharply once regional lymph nodes are involved. Neoadjuvant therapy is recommended for clinically node-positive disease to improve resectability and address micro-metastatic spread; however, the supporting evidence remains limited. We systematically reviewed contemporary data on neoadjuvant strategies for penile SCC, including cytotoxic chemotherapy, radiotherapy, immunotherapy, and molecularly targeted agents. Methods: A systematic search of MEDLINE, EMBASE, ClinicalTrials.gov, and CENTRAL was conducted from inception to January 2026 in accordance with MECIR guidance. Eligible studies included patients with histologically confirmed penile cancer treated with neoadjuvant intent prior to curative surgery. Primary outcomes were objective response rate (ORR), pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Data were synthesised narratively by treatment modality. Results: Forty-two studies met the inclusion criteria (32 chemotherapy, five radiotherapy, five immunotherapy, three targeted therapy). The evidence base was dominated by retrospective cohorts with limited prospective phase II data and no completed randomised trials. Across chemotherapy studies, the median reported ORR was 50% (range 29–90%), with pCR/ypN0 rates ranging 10–25%. Median reported PFS and OS were approximately 11 and 18 months, respectively, with durable survival concentrated among responders undergoing complete surgical consolidation. Radiotherapy data were sparse and heterogeneous. Early-phase immunotherapy combinations reported higher short-term response and pCR signals than historical chemotherapy, though the results were based on small single-arm cohorts. Molecularly targeted systemic monotherapy demonstrated modest activity. Conclusions: Neoadjuvant taxane–platinum-based chemotherapy remains the guideline-supported standard for cN2-3 penile SCC, supported by phase II and retrospective data but limited by methodological heterogeneity and absence of randomised evidence. Emerging combination immunotherapy strategies show promising efficacy signals and warrant prospective validation within biomarker-informed trial frameworks. Full article
(This article belongs to the Special Issue Advances in the Treatment of Urological Cancer)
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10 pages, 1668 KB  
Technical Note
Unilateral Biportal Endoscopic en Bloc Resection of the Lumbosacral Ligament Following Bony Release: A Technique Aiming to Reduce Dorsal Root Ganglion Manipulation
by Cheng-Ying Lee, Cheol-Wung Park, Man-Kyu Park, Wei-Yu Lee and Chien-Min Chen
J. Clin. Med. 2026, 15(10), 3765; https://doi.org/10.3390/jcm15103765 - 14 May 2026
Abstract
Background: Far-Out Syndrome at the lumbosacral junction is caused by extraforaminal compression of the L5 nerve root, frequently involving the lumbosacral ligament (LSL). Conventional piecemeal resection of the LSL may increase the risk of postoperative dysesthesia due to repeated manipulation near the [...] Read more.
Background: Far-Out Syndrome at the lumbosacral junction is caused by extraforaminal compression of the L5 nerve root, frequently involving the lumbosacral ligament (LSL). Conventional piecemeal resection of the LSL may increase the risk of postoperative dysesthesia due to repeated manipulation near the L5 dorsal root ganglion (DRG). This study introduces a novel unilateral biportal endoscopic (UBE) technique for en bloc resection of the LSL. Methods: The technique is based on an osteoclastic release strategy in which the bony attachments of the LSL, including the inferior aspect of the L5 transverse process and the sacral ala, are drilled and released before addressing the ligament itself. This maneuver elevates the LSL away from the underlying L5 DRG and achieves en bloc removal under direct endoscopic visualization. Results: En bloc resection may improve visualization within the narrow extraforaminal corridor and may reduce direct mechanical manipulation of the L5 DRG, which could potentially translate into reduced postoperative dysesthesia. The presented technique enabled effective decompression without repeated instrument insertion beneath the ligament. Conclusions: UBE-assisted en bloc resection of the LSL is a feasible and potentially neuroprotective technique for treating lumbosacral extraforaminal lesions. Full article
(This article belongs to the Section General Surgery)
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