Synchronous and metachronous liver metastases (LM) of colorectal cancer (CRC) drastically worsen the patient's survival. The biological and immunological mechanisms underlying these distinct metastatic trajectories remain incompletely understood. Prognostic impact of macrophages in primary CRC (pCRC) is uncertain, with discrepant findings reported for different macrophage subsets and different stage of the disease. Most of prior studies of tumor-infiltrating macrophages in CRC have focused primarily on the tumor core or invasive margin, whereas less attention has been given to the adjacent nontumor mucosa (NM), which may harbor early immunological alterations that precede or accompany metastatic spread.

To evaluate distribution and prognostic value of macrophages in pCRC and NM in patients at stage I-III vs IV.

Paired specimens of pCRC and NM were collected retrospectively from: (1) Stage IV (n = 55) patients with synchronous LM; and (2) Stage I-III (n = 44) patients who developed metachronous LM thereafter. After immunohistochemical staining CD68+ (M0), CD80+ (M1), CD206+ and CD163+ (M2) macrophages were quantified in NM and tumor center (TC) of pCRC. Cell densities in NM and TC and TC/NM ratios were tested as prognostic variables for overall survival since liver surgery. Cox-regression and Kaplan-Meier analyses were applied using the R environment.

Densities of macrophages followed the declining pattern from CD163+ through CD206+ and CD68+ to CD80+ in both NM and TC, with significantly smaller densities of all cell types in tumors. Greater densities of CD80+ cells were observed in NM in stage I-III over stage IV patients: 309 (24-1143) cells/mm² vs 208 (3-1084) cells/mm² [median (minimum-maximum), P = 0.04]. High CD163+ cell density in NM in stage IV [hazard ratio = 0.45 (95%CI: 0.22-0.95), P = 0.04] and CD80+ cell density in NM in stage I-III [hazard ratio = 0.24 (95%CI: 0.10-0.57), P = 0.001] were associated with longer overall survival.

Contrary to TC of pCRC, we found favorable prognostic implications of macrophages in NM, driven by distinct subsets of macrophages in stage IV (CD163+ M2) and stage I-III CRC (CD80+ M1).

To investigate the association between pretreatment controlling nutritional status (CONUT) score and clinical outcomes for cancer patients treated with immune checkpoint inhibitors (ICIs).

We conducted a comprehensive literature search of PubMed, Web of Science, Medline and Embase from inception of the databases to November 2025 to identify eligible studies concerning the relationship between pretreatment CONUT and survival outcomes in cancer patients treated with ICIs. Published data were extracted and risk ratio (RR) for objective response rate (ORR), disease control rate (DCR), and hazard ratio (HR) for overall survival (OS), progressive-free survival (PFS), along with 95% confidence intervals (CIs) were pooled. Data were analyzed using Stata14.0 software.

Ten studies involving 747 participants were included in this study. Patients were divided into low CONUT group and high CONUT group according to the cut-off value of CONUT score. Patients in high CONUT group had worse ORR and DCR than those in low CONUT group (RR 1.39, 95%CI 1.04-1.86;RR 1.64, 95%CI 1.32-2.03). Patients in high CONUT group had shorter PFS and OS than those in low CONUT group (1.71, 95%CI 1.21-2.42; 1.95, 95%CI 1.21-3.14). Subgroup analysis of cut-off value showed that PFS and OS of patients in high CONUT group were significantly shorter with a cut-off value of 3, and PFS of patients in high CONUT group were also worse than those of patients in the low CONUT group. Subgroup analysis of country indicated that both patients from Japan in high CONUT group had worse PFS and OS than those in low CONUT group, the OS of patients from China in high CONUT group was shorter than those in low CONUT group.

The CONUT score has potential value as an effective biomarker for the efficacy and prognosis of cancer patients treated with ICIs. In the future, large-scale prospective cohort studies should be conducted to determine the optimal cut-off value of CONUT, and to explore whether early and proactive nutritional and anti-inflammatory support based on CONUT score can reverse the adverse prognosis.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42022378362, identifier CRD42022378362.

We describe a new surgical approach for simultaneous liver and kidney transplant in which we utilized the same reverse L incision used for liver transplant to perform ipsilateral native nephrectomy and kidney transplant. The 48-year-old male patient had auto-somal dominant polycystic kidney and significant polycystic liver disease. He underwent multidisciplinary assessment and was listed for simultaneous liver and kidney transplant. The liver and kidney graft were donated from a donor after neurological determination of death. After hepatectomy and orthotopic liver transplant, a right native nephrectomy was performed followed by kidney transplant using the same incision. The transplanted kidney was placed on the right-hand side, with renal artery anastomosed to the external iliac artery, the renal vein anastomosed to the external iliac vein, and the ureter anastomosed to the end of the retained distal native ureter (ureteroureterostomy). Both liver and kidney graft had immediate function after transplant. This case highlights the feasibility and efficiency of a single reverse L incision approach for simultaneous liver and kidney transplant combined with a right-side nephrectomy.

Chondrosarcoma is a rare bone malignancy with a poor response to systemic therapy in advanced stages. European-level epidemiological data remain scarce. This study aimed to characterise patient demographics, treatments and survival using real-world data to inform regulatory decisions about the feasibility and design of new trials for the systemic treatment of chondrosarcoma. Patient/material and methods: This cohort study, part of the DARWIN EU® initiative, analysed data from six healthcare databases in Finland, France, the Netherlands, Spain and the UK. Patients diagnosed with chondrosarcoma between 2010 and 2022 were identified. Standardised analyses were performed within a federated network using the Observational Medical Outcomes Partnership (OMOP) Common Data Model.

A total of 2,498 chondrosarcoma patient records were identified, covering at least 2,356 unique patients. Median age at diagnosis was 52-55 years, with a balanced sex distribution. Surgical treatment was the most common intervention, recorded in 15.2% to 88.9% of patients, depending on the database. Fewer than 5% received systemic anticancer therapy, and radiotherapy was reported in fewer than 7%. The 10-year overall survival (OS) ranged from 58% (95% confidence interval [CI]: 43-78) to 80% (95% CI: 78-82), with restricted mean survival between 7.4 and 8.7 years. In the Netherlands, patients with late-stage, metastatic or high-grade disease showed significantly poorer outcomes.

This study demonstrates the feasibility of using real-world data across Europe to describe chondrosarcoma patients. Most had early-stage, low-grade disease amenable to surgery, with limited use of systemic therapies. Survival was generally favourable, except in advanced disease. Clinical trials remain difficult due to the rarity of advanced chondrosarcoma and the lack of standards.

Accurate dose prediction is challenged by the lack of available training samples and the rapid evolution of radiotherapy techniques.

A cross-technique transfer learning strategy was developed to predict the dose distribution for radiotherapy planning using limited training samples.

Data were collected from 154 patients with nasopharyngeal carcinoma: 60 treated with intensity-modulated radiotherapy (IMRT) and 94 treated with volumetric modulated arc therapy (VMAT). The Res-U Net was selected as the base deep learning network. Cross-technique models were pretrained on the IMRT dataset and subsequently fine-tuned on VMAT data using limited samples (five and seven cases). Independent models were trained from scratch using the same limited samples, while a standard model trained on the full VMAT training set served as the reference. Model performance was evaluated on a test set using metrics including the dose-volume histogram (DVH), voxel-based mean absolute error (MAE), and the Dice similarity coefficient (DSC) of the isodose volume.

The cross-technique models exhibited clinically acceptable performance with only five training samples and were comparable to the standard model (MAE deviation: 0.15%, p > 0.01 after Bonferroni correction; DSC deviation: 0.11%-0.72%). Performance improved further with seven training samples (MAE deviation: 0.05%, p > 0.01; DSC deviation: 0.02%-0.40%). However, the independent models trained with five or seven samples showed significantly inferior performance (five samples: MAE deviation: 1.14%, p < 0.01, DSC deviation: 0.98%-2.48%; seven samples: MAE deviation: 0.50%, p < 0.01, DSC deviation: 0.48%-1.05%).

The cross-technique models accurately and reliably predicted the dose distribution for a new radiotherapy technique using a limited sample size.

To evaluate the safety, feasibility, and short-term reliability of transvaginal sonography-guided ovarian cyst aspiration in women with benign-appearing ovarian cysts and to explore its potential economic and environmental implications compared with minimally invasive surgical management.

This retrospective cohort study included women with sonographically benign ovarian cysts treated with transvaginal sonography-guided aspiration at a tertiary-care hospital between January 2024 and October 2025. Patient characteristics, cyst morphology according to International Ovarian Tumor Analysis (IOTA) Simple Rules, procedural feasibility, complications, and recurrence rates were analyzed. In addition, targeted literature reviews were performed to contextualize reported health care costs and carbon footprints of laparoscopic gynecologic procedures.

Twenty-two women were included. The median age was 58 years (range 31-87), the median cyst diameter was 5.9 cm (range 2.8-10.0), and the median aspirated volume was 55 mL (range 9-600). All cysts fulfilled benign sonographic criteria, most commonly IOTA pattern B1 (77.3%), and were predominantly located in the Douglas space (77.3%). The procedure was technically feasible in 95% of cases and was performed under local anesthesia in all but one patient. No major intra or post-interventional complications occurred. One cyst recurrence (4.5%) was documented during follow-up, noting that most patients were assessed only via self-presentation. Literature data indicate substantially higher health care costs for laparoscopic and robotic gynecologic procedures compared with sonography-guided interventions. Published studies report a mean carbon footprint of approximately 42 kg CO²e per laparoscopic procedure, while no data are currently available for sonography-guided cyst aspiration.

Transvaginal sonography-guided ovarian cyst aspiration appears to be a safe and feasible treatment option for carefully selected benign ovarian cysts, with low short-term recurrence and minimal morbidity. Available evidence suggests potential economic advantages and a likely lower environmental impact compared with minimally invasive surgery. Given the small sample size, this approach should be considered a complementary or alternative option in selected patients rather than a first-line treatment and warrants further evaluation in larger prospective studies.

This research analyzes the global landscape of clinical trials focusing on therapies targeting the Nectin cell adhesion molecule 4 (Nectin-4) across various malignancies, using data from the Trialtrove database. Analysis of 136 interventional trials reveals a rapidly expanding field dominated by antibody-drug conjugates, particularly in urothelial carcinoma, with significant activity in combination regimens and diverse therapeutic modalities under exploration. These findings emphasize the substantial translational potential of Nectin-4 and highlight key trends shaping its future clinical development.

Hypothalamic hamartomas (HH) are rare brain lesions associated with epilepsy and numerous comorbidities. Worldwide treatment is varied. There is a paucity of high-quality evidence to guide treatment. This study aimed to establish expert consensus on the evaluation and management of HH.

A modified Delphi survey was designed by the Medical Advisory Board of Hope for Hypothalamic Hamartomas and was conducted among 17 International League Against Epilepsy level II epilepsy surgery centers. The survey included 257 questions in round 1 and 81 refined questions in round 2, covering domains of diagnosis, imaging, medical and surgical treatment, neuropsychological and psychiatric evaluation, and care. Consensus was defined as ≥75% agreement using a 9-point Likert scale.

Consensus was achieved on 82% of the questions. Key findings include the following: Diagnosis: Gelastic and dacrystic seizures are strongly associated with HH; 3T epilepsy protocol MRI is essential. Evaluation: Preoperative neuropsychological and endocrinologic assessments are important. Evaluation with further imaging (PET, SPECT, and magnetoencephalography) and intracranial EEG is not useful. Treatment: No consensus was achieved on first-line, second-line, or third-line antiseizure medications (ASMs). Surgical evaluation should begin at the start of the first ASM, with surgery recommended after failure of 2 ASMs. LITT is preferred for Delalande II and III HH. Postoperative care: MRI follow-up at 6-12 months recommended. Preoperative and postoperative cognitive, behavioral, psychosocial, and endocrinologic evaluations are emphasized. Domains: IQ, language, attention, executive function, academic achievement, adaptive function, and behavior (tantrums, rage, anxiety, and depression) are important.

This Delphi process highlights an international consensus on aspects of HH management. Gelastic/dacrystic seizures are important at diagnosis. A 3T epilepsy protocol MRI is essential. Early epilepsy surgery evaluation is advised. Surgery should be pursued either by disconnective, ablative, or resective techniques. HH location, size, and surgical experience are essential for good outcomes. Postoperative MRI should be obtained 6-12 months and/or if ongoing seizures. Neuropsychological testing should be obtained at baseline, and 6-12 months postsurgically. Findings support a multidisciplinary, protocol-driven approach to optimize outcomes in patients with HH. Areas lacking consensus, such as specific endocrine testing and timing of certain interventions, warrant further research and standardization.

Although the clinicopathologic features of BRAF/NRAS-mutant melanoma are well defined, the molecular landscape, clinicopathologic features, and treatment outcomes of BRAF/NRAS wild-type (WT) patients on immune checkpoint inhibitors (ICIs) remain less clear. The MatchMEL study investigated the mutational profile of WT melanoma (Part 1) and examined whether targeted treatments could be matched to specific molecular alterations with clinical activity (Part 2). We report findings from Part 1 only, focusing on the genomic landscape and clinicopathologic correlates in ICI-treated patients.

In Part 1, consecutive patients with advanced melanoma at two Australian centers were enrolled. BRAF/NRAS WT patients underwent FoundationOneCDx (F1CDx) sequencing. Clinical, pathologic, and treatment data were collected. Patients were stratified by mutational status (BRAF, NRAS, NF1, triple WT), and associations between tumor mutational burden (TMB), overall response rates (ORR), and survival outcomes (progression-free survival [PFS]) were analyzed using logistic regression and Kaplan-Meier methods. A molecular tumor board analyzed F1CDx results to match targeted therapy to molecular alterations. Part 2 assessed outcomes for patients treated with matched targeted therapies.

From 2021 to 2023, 210 patients were enrolled. Fifty-seven (27%) had BRAF V600 mutation, 53 (25%) had NRAS mutation, and 100 (48%) were BRAF/NRAS WT. Of these, 86 underwent profiling; NF1 mutations were detected in 37 (43%) and were associated with the highest median TMB (53 mut/Mb). NF1-mutant melanoma had a numerically longer median PFS (26.8 months [95% CI, 20.2 to not reached]; P = .58) and higher ORR (63%; P = .67) to first-line ICIs than other subtypes.

Our findings suggest significant clinical, pathologic, and molecular correlations in an Australian cohort of advanced melanoma treated with ICIs. Patients with NF1 mutation exhibited higher TMB, which was associated with improved response to ICIs.

A comprehensive understanding of newly described tumors is often an evolutionary process. In this study, we describe the extended spectrum of morphologic patterns in a cohort of 144 ALK fusion Spitz neoplasms and provide the largest data set of ALK fusion Spitz with clinical follow-up. In addition to the most classic morphologic pattern of a nodular silhouette with wavy fascicles of spindle cells, these tumors may also form a desmoplastic pattern, a combined nevus of Reed-Spitz pattern, a predominantly epithelioid pattern, and a nevoid pattern. There are genomic correlates to some of these morphologic patterns, with Reed-Spitz cases frequently having TPM4 as the fusion partner (P=0.001), epithelioid cases frequently having EHBP1 as the fusion partner (P=0.0002), and nevoid cases frequently having KIF5B as the fusion partner. Two fusion partners, ZEB2 and EML4, were only seen in Spitz melanoma (SM) cases. TERT promoter mutations and c-MYC amplification were only seen in SM. A meta-analysis of the literature suggests that adverse events tend to be associated with c-MYC amplification, CDKN2A homozygous deletion, and higher mitotic count (5.5 mitoses/mm2 in metastatic cases vs. 2.2 mitoses/mm2 in nonmetastatic cases). Our study expands the morphologic spectrum and the associated genomic correlates of ALK-rearranged Spitz neoplasms and identifies parameters associated with malignant behavior.