Search Results (48)

Background: Huriez syndrome is a rare hereditary skin disorder marked by early-onset sclerodactyly, hyperkeratosis of the palms and soles, and nail dysplasia. A key concern is the early and aggressive development of cutaneous squamous cell carcinoma (SCC), typically affecting the dorsal aspects of the hands. Methods: This narrative review summarizes clinical features, genetic aspects, and oncologic implications of Huriez syndrome. A systematic search was conducted in PubMed and Scopus, including English-language articles published up to May 2025. Relevant case reports and small case series were analyzed. Results: Seven patients (58.3%) underwent multiple surgeries due to recurrent or bilateral disease. Six patients (50%) required amputations, including finger, hand, and arm amputations, with no foot amputations reported. Reconstruction after oncological resection was performed in six patients (50%) using skin grafts (3), pedicled flaps (2), or free flaps (1). Amputation was mainly for advanced disease, with radial forearm flaps used for reconstruction. All flaps remained disease-free. Five cases (41.6%) had a history of local recurrence. Conclusions: The early diagnosis of Huriez syndrome is crucial to enable the surveillance and timely treatment of SCC. A multidisciplinary team including dermatologists, oncologists, plastic surgeons, and geneticists is recommended. Further research is needed to clarify genetic mechanisms and develop early detection strategies to improve outcomes. Full article

Background: Colorectal carcinoma (CRC) is one of the most common cancer types along with breast, prostate, and lung cancer. Many patients with CRC present with metastatic disease despite receiving standard first- and second-line therapies; thus emerges the demand for implementing new therapies that could improve outcomes among CRC patients. This case series was conducted to assess the efficacy and safety of regorafenib plus 5-fluorouracil (5-FU) in patients with refractory metastatic CRC (mCRC). Methods: We conducted a retrospective analysis of data from adult patients aged 18 and above who were diagnosed with refractory mCRC and received regorafenib plus 5-FU combination therapy at Houston Methodist Hospital between November 2017 and October 2023. Our study focuses on assessing key outcomes, including Overall Survival [OS], Progression-Free Survival [PFS], and safety. Results: Among the 12 patients we included in this study who underwent regorafenib plus 5-FU combination therapy for refractory mCRC after receiving at least three prior lines of treatment, the best response for six patients (50%) was successfully achieved, with disease control within 7–12 weeks from therapy initiation. Patients had an overall good tolerance for this treatment regimen and reported only the most common adverse events, including Hand-Foot Syndrome (HFS), mucositis, and hypertension (HTN), which were mostly resolved with dose adjustment of medications. Conclusions: This study highlights that using a combination of regorafenib plus 5-FU can be a potential treatment option for patients with refractory mCRC. Additional research, including prospective clinical trials, is required to assess the effectiveness and safety of regorafenib and 5-FU combination therapy in comparison to other currently limited treatment options. Full article

Background: The use of regorafenib and 5-fluorouracil in the management of refractory metastatic colorectal cancer has gained increasing attention due to their demonstrated efficacy in extending the survival of patients with colorectal cancer. This study aims to discuss the effect of using regorafenib and 5-fluorouracil combination therapy in refractory metastatic colorectal cancer patients. Case Presentation: We present a case report of a 68-year-old female patient with KRAS G12D and PIK3CA mutations who was diagnosed with stage IV-C colon cancer. She was referred to hospice care and subsequently received therapeutic intervention with 56 cycles of regorafenib and 5-fluorouracil for 31 months while maintaining stable disease (SD). The patient exhibited good tolerance with minimal adverse effects, including Grade I-II Hand–Foot Syndrome. Conclusions: Our case showed the feasibility of using Regorafenib and 5-fluorouracil combination therapy in stage IV refractory metastatic colorectal cancer treatment, which resulted in an improvement in the overall survival after she was referred to Hospice care. Utilizing this case report may provide valuable input in managing refractory metastatic colorectal cancer, given the prolonged survival and the clinical meaningfulness of this regimen in our patient. Full article

Background: Split-hand/foot malformation (SHFM) is a rare congenital limb anomaly defined by the absence or hypoplasia of the central rays of the autopod. SHFM occurs as an isolated entity or part of genetic syndromes with several causative copy-number variations or monogenic alterations known to be involved in the disease pathomechanism. On the other hand, cleft lip/palate (CL/P) usually results from polygenic and environmental factors, with the complex interplay of both leading to this malformation. Pathogenic variants in FGFR1 have been linked to phenotypically distinct disorders, including Hartsfield syndrome, Kallmann syndrome, Jackson–Weiss syndrome, osteoglophonic dysplasia, and Pfeiffer syndrome. Although pathogenic variants in FGFR1 can contribute to syndromic SHFM or CL/P, their role in isolated SHFM or CL remains poorly described in the literature. Methods: We conducted targeted next-generation sequencing (NGS) in the proband with SHFM, followed by segregation analysis in the family members. Results: In this study, we report an index patient presenting with isolated SHFM and his brother with CL and facial dysmorphism, as well as their father with isolated hyposmia. Targeted next-generation sequencing revealed a previously reported heterozygous missense pathogenic variant in FGFR1 (c.830G>A; p.Cys277Tyr) in both affected siblings and their hyposmic father. Conclusions: This study expands the phenotypic spectrum associated with FGFR1 pathogenic variants, emphasizing their involvement in non-syndromic SHFM and CL or isolated hyposmia. Our findings highlight the importance of considering FGFR1 in the molecular diagnosis of isolated SHFM or orofacial clefting, point to the high intrafamilial variability of FGFR1 pathogenic variants, and demonstrate the diagnostic value of targeted NGS in rare congenital malformations. Full article

Background and Objectives: Differentiated thyroid cancer is the predominant form of endocrine cancer, with most cases being treatable. However, some patients develop resistance to traditional treatments. This review examines the use of the new multi-kinase inhibitors surufatinib and sonafenib, which target pathways related to angiogenesis and tumor growth in these patients. Methods: An extensive search of the literature was performed to find research involving these drugs in treating differentiated thyroid cancer. Four relevant studies were found, including two each for surufatinib and donafenib. Information regarding the research design, participant details, treatment methods, results on effectiveness, and side effects was collected and analyzed. Results: Surufatinib showed encouraging results, with response rates between 23.2% and 60% and progression-free survival times as long as 11.1 months. Donafenib also demonstrated improved progression-free survival times (12.9 months) compared to a placebo (6.4 months) and had response rates as high as 23.3%. Both drugs were well tolerated, with the most frequent side effects being hypertension and hand−foot syndrome. Conclusions: Both urufatinib and donafenib offer substantial benefits for patients with advanced differentiated thyroid cancer and have acceptable safety profiles. These results support their potential inclusion in treatment strategies for resistant cases, and further investigation of their clinical application is recommended. Full article

Background/Objectives: Desmoid-type fibromatosis (DTF) is a locally invasive tumor composed of myofibroblast-like cells and collagen; it does not metastasize but can cause significant local morbidity. Most sporadic cases are associated with mutations in the CTNNB1 gene, which encodes beta-catenin. Various treatments have been used with differing efficacy and toxicity profiles. At our institution, pegylated liposomal doxorubicin (PLD) has become the preferred treatment for patients with DTF. We aim to describe our experience using PLD in patients with DTF who require treatment. Methods: A retrospective review of 61 DTF patients (41 females, 20 males) treated between 2000 and 2023 was conducted to assess the efficacy and toxicity of PLD. Results: Of the 26 patients treated with PLD, 23 had follow-up clinical data to assess benefit. Twenty-one showed clinical benefit, and only one progressed. Two patients did not benefit from PLD due to infusion reactions and chose alternative therapies. The primary side effect of PLD was hand-foot syndrome (HFS), but dose reduction and extended intervals allowed most patients to tolerate treatment. Other treatments, such as methotrexate, vinblastine/vinorelbine, and sorafenib, also showed activity but had significant toxicities, including severe HFS, malaise, and hypertension. Interestingly, 31 out of 61 patients had a pre-existing history of psychiatric conditions (primarily depression and anxiety), and 6 of 41 women had personal or family history of polycystic ovary syndrome (PCOS). Additionally, 15 patients had obesity, and 4 had hypothyroidism. Conclusions: PLD is an effective and well-tolerated treatment for DTF, with good clinical responses at lower, tolerable doses. The association of pre-existing psychiatric diagnoses, PCOS, and obesity warrants further investigation. Full article

Background and Aims: During liver transplantation, hepatocellular carcinoma (HCC) recurrence remains a critical challenge for patient survival. Targeted therapies, such as sorafenib and regorafenib, have been utilized to manage relapsed HCC in this unique setting. This study aimed to assess the efficacy of Sorafenib and Regorafenib in patients with HCC who experienced recurrence after liver transplantation. We focused on survival outcomes, treatment responses, and the management of side effects in this patient group. Methods: We conducted a retrospective analysis of 73 patients who experienced HCC recurrence post-liver transplantation between 2012 and 2022 across 11 oncology centers in Turkey. Patients were categorized according to Child–Pugh classification and treated with sorafenib as first-line therapy and Regorafenib in case of progression. Survival rates were analyzed using the Kaplan–Meier method, and risk factors were evaluated using Cox regression analysis. Results: Of the 73 patients included in the study, 62 were male (84.9%), and 11 were female (15.1%), with a mean age of 61.5 ± 10.9 years. All patients received sorafenib as first-line treatment. Among patients who experienced progression with sorafenib or discontinued treatment due to toxicity, 45.2% (n = 33) continued treatment with regorafenib. The median progression-free survival (PFS1) time with sorafenib was 5.6 months, and the one-year survival rate was 24.3%. The median progression-free survival (PFS2) time with regorafenib, which was administered as second-line treatment, was also calculated as 5.9 months. Overall survival (OS) duration was determined as 35.9 months. The most common side effects associated with both drugs included fatigue, hand and foot syndrome, and hypertension. Significantly better survival outcomes were shown in the Child–Pugh A group compared to other patients. Conclusions: These results suggest that Sorafenib and Regorafenib treatments offer a survival advantage in patients with relapsed HCC post-transplantation. However, individualized treatment strategies and close follow-up are crucial for optimizing outcomes. Further studies are needed to refine therapeutic protocols and enhance the care of this specific patient group. Full article

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with a median overall survival (OS) of 15–18 months despite standard treatments. Approximately 8% of GBM cases exhibit genomic alterations in fibroblast growth factor receptors (FGFRs), particularly FGFR1 and FGFR3. Next-generation sequencing techniques have identified various FGFR3 fusions in GBM. This report presents a novel FGFR3 fusion with fatty acid synthase (FASN) in a 41-year-old male diagnosed with GBM. The patient presented with a persistent headache, and imaging revealed a right frontal lobe lesion. Surgical resection and subsequent histopathology confirmed GBM. Initial NGS analysis showed no mutations in the IDH1, IDH2 or H3F3 genes, but revealed a TERT promoter mutation and CDKN2A/2B and PTEN deletions. Postoperative treatment included radiotherapy and temozolomide. Despite initial management, recurrence occurred four months post-diagnosis, confirmed by MRI and histology. A second surgery identified a novel FGFR3-FASN fusion, alongside increased Ki67 expression. The recurrence was managed with regorafenib and bevacizumab, though complications like hand–foot syndrome and radiation necrosis arose. Despite initial improvement, the patient died 15 months after diagnosis. This case underscores the importance of understanding GBM’s molecular landscape for effective treatment strategies. The novel FGFR3-FASN fusion suggests potential implications for GBM recurrence and lipid metabolism. Further studies are warranted to explore FGFR3-FASN’s role in GBM and its therapeutic targeting. Full article

Objective: To investigate the long-term effects of intravenous neridronate treatment in patients with complex regional pain syndrome type 1 (CRPS) in a real-life setting. Methods: We conducted a retrospective study on consecutive CRPS patients treated at our hospital from February 2018 to July 2023. All were treated within three months of the onset of CRPS symptoms. The Patient-Reported Outcomes Measurement Information System 29-Item Health Profile (PROMIS-29) version 2.1 was administered. The main outcome of interest was the evolution of the PROMIS-29 scores from baseline to the last follow-up visit. Patients were categorized as “complete responders” or “non-complete responders”. The association of clinical and demographic variables with a complete response was analyzed using chi-square tests and univariate logistic regression. Results: Thirty-six patients were included, with a median follow-up time of 4.8 years. A significant improvement was noted in the mean numerical pain rating scale (from 6.4 ± 1.9 to 3.1 ± 2.4, p < 0.001), as well as across all PROMIS-29 domains. Physical function improved from 34.2 ± 4.9 to 49.2 ± 9.9, p < 0.001; anxiety from 58.0 ± 6.7 to 49.6 ± 6.9, p < 0.001; depression from 55.3 ± 6.3 to 47.7 ± 6.6, p < 0.001; fatigue from 55.7 ± 7.7 to 50.9 ± 8.7, p < 0.001; sleep disturbance from 53.8 ± 6.8 to 51.3 ± 6.6, p = 0.034; social roles and activities from 41.8 ± 5.2 to 51.8 ± 8.9, p < 0.001; and pain interference from 64.1 ± 5.9 to 52.4 ± 9.9, p < 0.001. The likelihood of achieving a complete response was associated with the male sex, foot or ankle injuries (compared to hand and wrist injuries), and a younger age. No association was found with the type of inciting event or with the body mass index. Conclusions: Our real-life data indicate that early treatment with neridronate leads to substantial benefits in patients affected by CRPS type 1. The strongest responses are seen in young patients, males, and those with lower limb involvement. Full article

To assess the impact of adverse event (AE) severity, caused by targeted therapy, on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC), a total of 183 patients with HCC treated with atezolizumab plus bevacizumab (40), lenvatinib (57), sorafenib (79), cabozantinib (3), ramucirumab (3), and regorafenib (1) were included in this study. Age-, AFP-, and ALBI score-adjusted hazard ratios (HRs) of AE grades 1 to 3 versus grade 0 for OS and PFS were calculated using Cox proportional hazards models. The linear trend of the HRs was assessed by calculating the p values for this trend. The most common AEs were appetite loss (AE grade 0/1/2/3 = 97/23/55/12), general fatigue (102/31/44/6), hypertension (120/6/40/17), hand-foot syndrome (HFS) (135/21/24/3), proteinuria (140/13/16/14), and hypothyroidism (148/12/23/0). The adjusted HRs for OS of these AEs were 0.532–1.450–2.361 (p for trend 0.037), 1.057–1.691–3.364 (p for trend 0.004), 1.176–0.686–0.281 (p for trend 0.002), 0.639–0.759–1.820 (p for trend 0.462), 1.030–0.959–0.147 (p for trend 0.011), and 0.697–0.609 (p for trend 0.119), respectively. Those for PFS of the corresponding AEs were 0.592–1.073–2.811 (p for trend 0.255), 1.161–1.282–4.324 (p for trend 0.03), 0.965–0.781–0.655 (p for trend 0.095), 0.737–0.623–2.147 (p for trend 0.153), 1.061–0.832–0.800 (p for trend 0.391), and 1.412–0.560 (p for trend 0.081), respectively. Appetite loss and general fatigue negatively affected clinical outcomes, whereas hypertension, HFS, proteinuria, and hypothyroidism had positive effects. Full article

Ultrasound imaging is a vital imaging tool in musculoskeletal medicine, with the number of publications on ultrasound-guided surgery increasing in recent years, especially in minimally invasive procedures of sports, foot and ankle, and hand surgery. However, ultrasound imaging has drawbacks, such as operator dependency and image obscurity. Artificial intelligence (AI) and deep learning (DL), a subset of AI, can address these issues. AI/DL can enhance screening practices for hip dysplasia and osteochondritis dissecans (OCD) of the humeral capitellum, improve diagnostic accuracy for carpal tunnel syndrome (CTS), and provide physicians with better prognostic prediction tools for patients with knee osteoarthritis. Building on these advancements, DL methods, including segmentation, detection, and localization of target tissues and medical instruments, also have the potential to allow physicians and surgeons to perform ultrasound-guided procedures more accurately and efficiently. This review summarizes recent advances in ultrasound-guided procedures for musculoskeletal diseases and provides a comprehensive overview of the utilization of AI/DL in ultrasound for musculoskeletal medicine, particularly focusing on ultrasound-guided surgery. Full article

Introduction: Combinations of immune-checkpoint inhibitors (ICIs) are the standard of care (SOC) for treatment-naive metastatic renal cell carcinoma (mRCC) patients. In this multicenter study, we evaluated the RW safety and efficacy of cabozantinib plus nivolumab in mRCC patients. Methods: Data were retrospectively collected from twelve cancer centers in Germany, Switzerland, and Austria. Patients with advanced or mRCC were eligible. The investigator-based objective response rate (ORR) and progression free survival (PFS) were calculated from the start of the treatment to progression or death. Descriptive statistics and Kaplan–Meier (KM) plots were utilized where appropriate. Results: In total, 96 eligible patients (66.6% male) with a median age of 66.0 years were included. The most common histology was clear-cell RCC (ccRCC) in 63.4% (n = 61). A prior nephrectomy was performed in 60.4% (n = 58). ECOG 0-1 was 68.8% (n = 66). A partial response was documented in 43.8% of patients (n = 42), a stable disease in 32.3% (n = 31), and a progressive disease in 8.3% (n = 8) as the best overall response. Response data were not evaluable in 13.5% (n = 13). The median follow-up time was 12.7 months (95% CI, 10.0–15.3). The PFS rate at 6 months was 89.8% in the overall population (86.8% for ccRCC; 90.0% for non-ccRCC). Adverse events (AEs) were reported in 82.3% (n = 79) for all grades and 41.7% (n = 40) for grades 3–5. Elevated liver enzymes (34.4%), diarrhea (31.3%), and hand–foot syndrome (29.2%) were the three most frequent AEs of any grade and causality. Discussion/Conclusions: In this real-world cohort of mRCC patients, the application of cabozantinib plus nivolumab was shown to be safe and feasible. Our data support the use of cabozantinib plus nivolumab as a first-line standard therapy in mRCC patients. Major limitations were the retrospective data capture and short follow-up time of our study. Full article

Macrodactyly is a rare congenital limb difference manifesting as an overgrowth of one or more fingers or toes. The pathological process affects all tissues of the ray in the hand or foot. The enlargement can significantly alter the limb’s appearance and impair its function. The role of a pediatrician is to distinguish isolated macrodactyly from syndromic conditions (including PIK3CA-Related Overgrowth Spectrum) or mimicking conditions to enable early interdisciplinary consultation and treatment planning. The psychological stigma associated with this often disfiguring condition necessitates support for patients and their family. We present a practical guide for physicians who might be the first to raise suspicion of macrodactyly and initiate further diagnostics to achieve adequate treatment and support for children and caregivers. Full article

Background: Acute compartment syndrome is a major surgical emergency with complex pathophysiology and a highly unpredictable pattern of evolution. We hypothesized that the onset of acute compartment syndrome of the leg or forearm is associated with variations in the surface temperature of the distal segment (foot or hand) with a distinct pattern, which acts as an early warning sign. Materials and Methods: We developed a monitoring device that consists of two thermic sensors attached to a modular limb splint, which continuously measure the temperature difference between the proximal and distal regions of the limb (i.e., arm–hand, thigh–foot). Firstly, we investigated both the arm–hand and thigh–foot temperature gradients of hospitalized patients’ healthy limbs (43 patients, 56 upper limbs, 64 lower limbs) in order to establish a baseline. Secondly, we examined the correlation between the thermic gradients and intracompartmental pressure values in compartment syndrome limbs (20 patients, 6 upper limbs, 14 lower limbs). Results: For the control group, the mean values for the normal limb thermic gradients were −0.17 °C for the upper limbs. and 0.03 °C for the lower limbs. In the impending compartment syndrome group (defined by intracompartmental pressure values), the mean index was −0.38 °C. In the fully developed compartment syndrome group, the mean value was 4.11 °C. Discussions: Analysis was performed using the ANOVA one-way statistical method. This showed significant differences between the compartment syndrome group and the impending and control groups. A decreasing trend in the thermic gradient in patients with impending compartment syndrome compared with the control group was noted. Conclusions: The thermic gradient of limbs presenting signs of impending compartment syndrome decreases as a result of the increased temperature of the distal segment. This pattern can be used as an early diagnostic method for acute compartment syndrome. This technique is non-invasive and bears no risk to the patient, allowing facile continuous monitoring during immobilization. Full article

Cabozantinib, an oral inhibitor targeting MET, AXL, and VEGF receptors, has become a key component of a sequential treatment strategy for clear cell renal cell carcinoma (ccRCC). The purpose of this work is to show that effective management of adverse events (AEs) during cabozantinib treatment and achieving a balance between AEs and treatment efficacy is crucial to achieving therapeutic goals. In this retrospective study, involving seventy-one metastatic RCC (mRCC) patients receiving second or subsequent lines of cabozantinib at the Department of Genitourinary Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, we explored the impact of AEs on overall survival (OS) and progression-free survival (PFS). AEs were observed in 92% of patients. Hypothyroidism during treatment was significantly associated with prolonged OS and PFS (HR: 0.31; p < 0.001 and HR: 0.34; p < 0.001, respectively). The occurrence of hand–foot syndrome (HFS) was also linked to improved OS (HR: 0.46; p = 0.021). Patients experiencing multiple AEs demonstrated superior OS and PFS compared to those with one or no AEs (HR: 0.36; p < 0.001 and HR: 0.30; p < 0.001, respectively). Hypothyroidism and HFS serve as valuable predictive factors during cabozantinib treatment in ccRCC patients, indicating a more favorable prognosis. Full article