RESUMEN

Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.

Asunto(s)

RESUMEN

Autophagy is an evolutionarily conserved process that plays a pivotal role in the maintenance of cellular homeostasis and its impairment has been implicated in the pathogenesis of various metabolic diseases including obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD). This review synthesizes the current evidence from human studies on autophagy alterations under these metabolic conditions. In obesity, most data point to autophagy upregulation during the initiation phase of autophagosome formation, potentially in response to proinflammatory conditions in the adipose tissue. Autophagosome formation appears to be enhanced under hyperglycemic or insulin-resistant conditions in patients with T2D, possibly acting as a compensatory mechanism to eliminate damaged organelles and proteins. Other studies have proposed that prolonged hyperglycemia and disrupted insulin signaling hinder autophagic flux, resulting in the accumulation of dysfunctional cellular components that can contribute to ß-cell dysfunction. Evidence from patients with MASLD supports autophagy inhibition in disease progression. Nevertheless, given the available data, it is difficult to ascertain whether autophagy is enhanced or suppressed in these conditions because the levels of autophagy markers depend on the overall metabolism of specific organs, tissues, experimental conditions, or disease duration. Owing to these constraints, determining whether the observed shifts in autophagic activity precede or result from metabolic diseases remains challenging. Additionally, autophagy-modulating strategies are shortly discussed. To conclude, more studies investigating autophagy impairment are required to gain a more comprehensive understanding of its role in the pathogenesis of obesity, T2D, and MASLD and to unveil novel therapeutic strategies for these conditions.

Asunto(s)

RESUMEN

Tissue biopsy remains the standard for diagnosing gastrointestinal stromal tumors (GISTs), although liquid biopsy is emerging as a promising alternative in oncology. In this pilot study, we advocate for droplet digital PCR (ddPCR) to diagnose GIST in tissue samples and explore its potential for early diagnosis via liquid biopsy, focusing on the PDGFRA D842V mutation and SEPT9 hypermethylated gene. We utilized ddPCR to analyze the predominant PDGFRA mutation (D842V) in surgical tissue samples from 15 GIST patients, correlating with pathologists' diagnoses. We expanded our analysis to plasma samples to compare DNA alterations between tumor tissue and plasma, also investigating SEPT9 gene hypermethylation. We successfully detected the PDGFRA D842V mutation in GIST tissues by ddPCR. Despite various protocols to enhance mutation detection in early-stage disease, it remained challenging, likely due to the low concentration of DNA in plasma samples. Additionally, the results of Area Under the Curve (AUC) for the hypermethylated SEPT9 gene, analyzing concentration, ratio, and abundance were 0.74 (95% Confidence Interval (CI): 0.52 to 0.97), 0.77 (95% CI: 0.56 to 0.98), and 0.79 (95% CI: 0.59 to 0.99), respectively. As a rare disease, the early detection of GIST through such biomarkers is particularly crucial, offering significant potential to improve patient outcomes.

Asunto(s)

RESUMEN

Spinal tuberculosis is an uncommon extrapulmonary manifestation of tuberculosis infection, known as a great masquerade that often mimics other pathologies, such as pyogenic and non-pyogenic infection, bone metastasis, haematological malignancy, and metabolic bone disease. It presents great challenges in establishing a diagnosis, deciding on treatment, and monitoring the response to treatment. A tissue-proven diagnosis is the cornerstone of a definitive diagnosis before initiating medical antitubercular therapy, leading to successful treatment. Here, we present a distinct and rare instance of spinal tuberculosis with an atypical presentation of upper thoracic myelopathy. It involved the cervicothoracic junction, exhibiting minimal axial symptoms but intensive destruction of the affected levels radiologically, along with an incomplete neurological deficit and the possibility of catastrophic neurological complications. The ultimate distinctiveness of this case lies in the diagnostic challenge it posed. Despite undergoing three separate tissue biopsies, tuberculosis infection could not be established, as all results returned negative for cellular, molecular, and histopathological markers, leading to a delay in initiating empirical medical therapy. Nonetheless, the patient responded well to empirical antitubercular therapy, resulting in favourable outcomes. To the best of our knowledge, a case of spinal tuberculosis with numerous negative tissue diagnoses has not been previously reported.

RESUMEN

INTRODUCTION AND IMPORTANCE: Cutaneous Tuberculosis (CTB), elicited by the Mycobacterium tuberculosis complex, manifests dermatologically. The scarcity of bacilli within CTB lesions renders their detection challenging. This study presents a case of CTB, underscoring its rarity and the potential for severe complications that can deteriorate patient quality of life. It aims to highlight the importance of CTB identification in dermatological diagnoses due to its capacity to cause considerable morbidity and affect patients' psychosocial health. CASE PRESENTATION: An 18-year-old patient presented with a painful, well-defined reddish plaque on the right palm, originating five years prior, accompanied by contractures of the middle finger. The tender lesion, characterized by an irregular surface, exhibited purulent discharge upon light touch through fissures along its periphery. Management involved necrotomy, debridement, and tissue biopsy for diagnostic and reconstructive purposes. CLINICAL DISCUSSION: CTB exhibits a wide range of clinical presentations, often resembling other dermatological infections, which complicates its diagnosis. Accurate diagnosis necessitates an integrated approach involving clinical assessment, the tuberculin skin test, histopathological analysis, and bacteriological investigations. The therapeutic regimen includes multidrug anti-tuberculosis treatment, with surgical intervention reserved for specific cases. CONCLUSION: Long-term complications of untreated CTB encompass significant contractures, scarring, and the onset of carcinomas and sarcomas. Prompt diagnosis facilitates timely and effective treatment, averting these sequelae and yielding high patient satisfaction.

RESUMEN

OBJECTIVE: To describe a laparoscopic technique for ovarian tissue biopsy (OTB) for fertility preservation. In the last years, the demand for fertility preservation has grown because of the increasing survival rates among patients with cancer and the rising awareness of the importance of quality of life after gonadotoxic therapy. Among fertility-sparing approaches, ovarian tissue cryopreservation is a valid strategy to preserve ovarian endocrine and reproductive function in prepubertal and postpubertal women who will undergo gonadotoxic cancer treatments. Currently, there is no universal consensus regarding ovarian tissue retrieval technique for fertility preservation. DESIGN: Step-by-step description of the surgical technique with narrated video footage. SETTING: Academic tertiary hospital. PATIENT(S): Patients with a high risk of premature ovarian insufficiency, usually due to gonadotoxic treatments, who undergo OTB for fertility preservation were included in the study. In this video, we present the clinical case of a 28-year-old patient affected by Hodgkin lymphoma who underwent laparoscopy for OTB before chemotherapy. INTERVENTION(S): After exposing the chosen ovary, an incision at the tubal pole of the ovary is made with scissors. Through section and dissection, a large cortical biopsy of the ovary is performed without removing and avoiding any damage to the medulla. At the end of the procedure, hemostasis was achieved with selective coagulation using bipolar coagulation. MAIN OUTCOME MEASURE(S): Step by step educational video. RESULT(S): The post-operative course was uneventful and the patient was discharge 24 hours after surgery. CONCLUSION(S): Standardization of a step-by-step laparoscopic technique can provide an effective method to optimize ovarian tissue removal while minimizing tissue injury. Medulla-sparing ovarian biopsy allows retrieval of only the cortical part of the ovary, maximizing the number of primordial follicles obtained without damaging the vascular supply of the ovary contained within the medulla. Primordial follicles are resistant to cryoinjury owing to their relatively inactive metabolism, and they are usually found at approximately 0.8 mm below the surface of the cortex. This technique could also reduce the back-table processing time of the ovarian tissue before cryopreservation. One disadvantage could be the difficulty of the technique compared to an oophorectomy because it requires a skilled surgeon that can easily find the cleavage plane between the medulla and the cortex, even in patients submitted to previous chemoradiotherapy or during gonadotropin-releasing hormone analogue therapy.

Asunto(s)

RESUMEN

Objective:To observe the changes of pelvic floor structure and function in female vaginal laxity after CO 2 fractional laser transvaginal treatment. Methods:This study reviewed the improvement of pelvic floor structure and function after CO 2 fractional laser transvaginal treatment in 28 female patients [aged 26-59 (37.5±8.3) years] with vaginal laxity syndrome seen at the Department of Dermatology, the First Affiliated Hospital of Air Force Medical University from March 2020 to November 2021. A total of 28 female patients with vaginal laxity syndrome underwent intravaginal treatment by CO 2 fractional laser instrument once/month for 3 times. The clinical efficacy and safety were evaluated according to the pre- and post-treatment transverse vaginal diameter, FSFI score of female sexual function, VHIS score of vaginal environment, vaginal tactile imaging system (VTI), pelvic ultrasound and MRI, tissue biopsy, patient satisfaction, pain score, and postoperative adverse effects. Results:Twenty-one of the twenty-eight female patients with vaginal laxity syndrome showed significant improvement in symptoms related to vaginal laxity syndrome after intravaginal treatment with CO 2 fractional laser therapy. All patients showed improvement in all indexes before and 1 month after treatments the mean vaginal transverse diameter decreased from (3.00±0.39) fingers to (2.71±0.40) fingers ( P<0.05), VHIS increased from (17.12±3.97) to (21.69±3.61) ( P<0.05), FSFI score improved from (23.11±3.70) to (27.43±5.33) ( P<0.05), and VTI examination showed that vaginal muscle strength and elasticity were improved to different degrees, and there was a statistical difference compared with that before treatment (total contractility of the anterior vaginal wall: t=26.23, P<0.001; total contractility of posterior vaginal wall: t=39.02, P<0.001; the mean contractility of the anterior vaginal wall: t=17.92, P<0.001; the mean contractility of the posterior vaginal wall: t=22.57, P<0.001). At the same time, questionnaire score of international consultation on incontinent questionnaire short form (ICI-Q-SF scale) of 13 patients with combined mild to moderate stress urinary incontinence showed a statistically significant decrease compared with those before treatment (8.97±2.99 before treatment and (7.18±1.79) one month after treatment; t=2.792, P<0.01). Pelvic ultrasound and magnetic resonance examination indicated a tightening of the vaginal wall structure, and pelvic ultrasound observed a significant decrease in bladder neck mobility and a significant decrease in vesicourethral rotation angle. Vaginal tissue biopsy indicated an increase in the thickness of the vaginal mucosa and an increase in the number and more regular arrangement of collagen fibers after treatment. All patients had high treatment satisfaction and there were no adverse effects such as infection and bleeding during the treatment. Conclusions:Transvaginal CO 2 fractional laser treatment can improve the pelvic floor structure and function around the vagina, treat female vaginal laxity syndrome, stress urinary incontinence and female sexual dysfunction, with significant clinical efficacy and good safety.

RESUMEN

The diagnosis and management of hepatocellular carcinoma (HCC) have improved significantly in recent years. With the introduction of immunotherapy-based combination therapy, there has been a notable expansion in treatment options for patients with unresectable HCC. Simultaneously, innovative molecular tests for early detection and management of HCC are emerging. This progress prompts a key question: as liquid biopsy techniques rise in prominence, will they replace traditional tissue biopsies, or will both techniques remain relevant? Given the ongoing challenges of early HCC detection, including issues with ultrasound sensitivity, accessibility, and patient adherence to surveillance, the evolution of diagnostic techniques is more relevant than ever. Furthermore, the accurate stratification of HCC is limited by the absence of reliable biomarkers which can predict response to therapies. While the advantages of molecular diagnostics are evident, their potential has not yet been fully harnessed, largely because tissue biopsies are not routinely performed for HCC. Liquid biopsies, analysing components such as circulating tumour cells, DNA, and extracellular vesicles, provide a promising alternative, though they are still associated with challenges related to sensitivity, cost, and accessibility. The early results from multi-analyte liquid biopsy panels are promising and suggest they could play a transformative role in HCC detection and management; however, comprehensive clinical validation is still ongoing. In this review, we explore the challenges and potential of both tissue and liquid biopsy, highlighting that these diagnostic methods, while distinct in their approaches, are set to jointly reshape the future of HCC management.

Asunto(s)

RESUMEN

The impact of Candida sp. in the development of oral cancer remains uncertain and requires sensitive analytical approaches for clarification. Given the invasive capabilities of these microorganisms in penetrating and invading host tissues through hyphal invasion, this study sought to detect the presence of five Candida sp. in oral biopsy tissue samples from non-smoker patients. Samples were obtained from patients at varying stages of oral carcinogenesis, including dysplasia, carcinoma in situ, OSCC, and histologically benign lesions, and analyzed using Real-Time PCR. Oral tissue samples from 80 patients (46 males and 34 females) were included. Significantly higher C. albicans presence was detected in the mild/moderate dysplasia group compared to the healthy (p = 0.001), carcinoma in situ (p = 0.031) and OSCC groups (p = 0.000). Similarly, C. tropicalis carriage was higher in tissues with mild/moderate dysplasia compared to healthy (p = 0.004) and carcinoma in situ (p = 0.019). Our results showed a significant increase in the presence of C. albicans and C. tropicalis within the mild/moderate dysplasia group compared to other cohorts. Coexistence of these two microorganisms was observed, suggesting a potential transition from a commensal state to an opportunistic pathogen, which could be particularly linked to the onset of oral neoplasia.

RESUMEN

Gliomas comprise the most frequent primary central nervous system (CNS) tumors, characterized by remarkable genetic and epigenetic heterogeneity, difficulty in monitoring, and increased relapse and mortality rates. Tissue biopsy is an established method of tumor cell collection and analysis that enables diagnosis, classification of different tumor types, and prediction of prognosis upon confirmation of tumor's location for surgical removal. However, it is an invasive and often challenging procedure that cannot be used for frequent patient screening, detection of mutations, disease monitoring, or resistance to therapy. To this end, the minimally invasive procedure of liquid biopsy has emerged, allowing effortless tumor sampling and enabling continuous monitoring. It is considered a novel preferable way to obtain faster data on potential tumor risk, personalized diagnosis, prognosis, and recurrence evaluation. The purpose of this review is to describe the advances on liquid biopsy for glioma diagnosis and management, indicating several biomarkers that can be utilized to analyze tumor characteristics, such as cell-free DNA (cfDNA), cell-free RNA (cfRNA), circulating proteins, circulating tumor cells (CTCs), and exosomes. It further addresses the benefit of combining liquid biopsy with radiogenomics to facilitate early and accurate diagnoses, enable precise prognostic assessments, and facilitate real-time disease monitoring, aiming towards more optimal treatment decisions.

RESUMEN

The introduction of liquid biopsies (LB) has brought forth a number of therapeutic opportunities into the domain of thoracic oncology. Many of which have been adopted for care of patients presenting with advanced non-squamous non-small cell lung cancer (aNS-NSCLC). For example, one of the most frequent indications to perform a LB in these patients, at least in Europe, is for patients treated with tyrosine kinase inhibitors (TKIs) targeting EGFR and ALK genomic alterations when the tumor progresses. A tissue biopsy (TB) must then be taken, ideally from a site of a tumor that progresses, in particular if the LB does not permit detection of a mechanism of resistance to TKI. A LB from a patient with aNS-NSCLC is recommended before first-line therapy if no tissue and/or cytological material is accessible or if the extracted nucleic acid is insufficient in amount and/or of poor quality. At present a LB and a TB are rarely performed simultaneously before treatment and/or on tumor progression. This complementary/matched testing approach is still controversial but needs to be better evaluated to determine the true benefit to care of patients. This review provides an update on the complementarity of the LB and TB method for care of patients presenting with aNS-NSCLC.

RESUMEN

Hodgkin's lymphoma (HL) is a malignancy that is typically B-cell in origin. HL can be further classified into classical HL and nodular lymphocyte-predominant HL (NLPHL). NLPHL is a rare lymphoma. It commonly presents locally with palpable firm lymphadenopathy or mediastinal mass seen on chest imaging. Some patients may have B symptoms (fever, night sweats, and unintentional weight loss), splenomegaly, and hepatomegaly. We describe a case of NLPHL in a 32-year-old male with classical findings of this rare class of HL.

RESUMEN

INTRODUCTION: Losing of small tissues during tissue preparatory steps may seriously affect pathological diagnostic performance. Using an appropriate tissue marking dye could be an alternative solution. Therefore, the aim of the study was to find a suitable tissue marking dye to enhance the observable ability of various types of small-size tissues during several steps of tissue preparation. MATERIAL AND METHODS: Various small-size samples of various organs and tissues (0.2 to 0.3 cm), including breast, endometrial, and cervical tissue, stomach, small and large intestine, lung, and kidney, were marked with different dyes such as merbromin, hematoxylin, eosin, crystal violet, and alcian blue prior to tissue processing step and their colored-observable ability was evaluated by pathology assistants. Moreover, the diagnostic interfering effect of each tissue marking dye was determined by pathologists. RESULTS: Merbromin, hematoxylin, and alcian blue increased the colored-observable ability of small tissue samples. We suggest using hematoxylin as a tissue marking dye over merbromin and alcian blue because of less toxicity and no interference effect in the step of routine pathological slide examination. CONCLUSIONS: Hematoxylin could be a suitable tissue marking dye for small-size samples and may improve the preanalytical process of tissue preparation in pathological laboratories.

Asunto(s)

RESUMEN

This paper presents a combined optical imaging/artificial intelligence (OI/AI) technique for the real-time analysis of tissue morphology at the tip of the biopsy needle, prior to collecting a biopsy specimen. This is an important clinical problem as up to 40% of collected biopsy cores provide low diagnostic value due to high adipose or necrotic content. Micron-scale-resolution optical coherence tomography (OCT) images can be collected with a minimally invasive needle probe and automatically analyzed using a computer neural network (CNN)-based AI software. The results can be conveyed to the clinician in real time and used to select the biopsy location more adequately. This technology was evaluated on a rabbit model of cancer. OCT images were collected with a hand-held custom-made OCT probe. Annotated OCT images were used as ground truth for AI algorithm training. The overall performance of the AI model was very close to that of the humans performing the same classification tasks. Specifically, tissue segmentation was excellent (~99% accuracy) and provided segmentation that closely mimicked the ground truth provided by the human annotations, while over 84% correlation accuracy was obtained for tumor and non-tumor classification.

RESUMEN

OBJECTIVE: Diagnosing periprosthetic joint infection (PJI) can be challenging. The ability to distinguish between septic and aseptic failure of a joint prosthesis is crucial for treatment strategy optimisation and prognosis prediction. Preoperative tissue cultures are included in many diagnostic algorithms; however, studies report different degrees of concordance (63%-85%) with intraoperative cultures. This study aimed to investigate the diagnostic performance of tissue biopsies in the preoperative diagnostic process with the 2018 International Consensus Meeting criteria as a reference and to describe the concordance between microbiological findings in pre- and intraoperative biopsies. METHODS: This observational retrospective study included 44 patients requiring revision surgery of a total hip or knee arthroplasty, where the diagnostic workup included biopsies of periprosthetic tissue. The accuracy of preoperative biopsies was calculated, and concordance between microbiological findings in pre- and intraoperative biopsies was described. RESULTS: The accuracy was 59%, with a sensitivity of 50% and specificity of 79%. Full concordance between microbiological findings in pre- and intraoperative biopsies was found in 64% of the cases. CONCLUSION: An open biopsy of periprosthetic tissue cannot reliably confirm or exclude PJI, and, therefore, should not be performed.

Asunto(s)

RESUMEN

Diagnosis of superficial/cutaneous fungal infections from skin, hair and nail samples is generally achieved using microscopy and culture in a microbiology laboratory, however, any presentation that is unusual or subcutaneous is sampled by taking a biopsy. Using histological techniques a tissue biopsy enables a pathologist to perform a full examination of the skin structure, detect any inflammatory processes or the presence of an infectious agent or foreign body. Histopathological examination can give a presumptive diagnosis while a culture result is pending, and may provide valuable diagnostic information if culture fails. This review demonstrates how histopathology contributes to the diagnosis of fungal infections from the superficial to the life threatening.

Asunto(s)

RESUMEN

Oral squamous papillomas (SPs) are benign masses commonly growing in the tongue, gingiva, uvula, lips, and palate. A case of an asymptomatic pedunculated squamous papilloma at the center of the soft palate is presented. Both surgical management and histopathologic analysis were conducted. The aim of this report is to stress the importance of early diagnosis and management of common benign oral lesions to prevent their transformation into malignancy.

RESUMEN

Ophthalmic malignancies include various rare neoplasms involving the conjunctiva, the uvea, or the periocular area. These tumors are characterized by their scarcity as well as their histological, and sometimes genetic, diversity. Uveal melanoma (UM) is the most common primary intraocular malignancy. UM raises three main challenges highlighting the specificity of ophthalmic malignancies. First, UM is a very rare malignancy with an estimated incidence of 6 cases per million inhabitants. Second, tissue biopsy is not routinely recommended due to the risk of extraocular dissemination. Third, UM is an aggressive cancer because it is estimated that about 50% of patients will experience metastatic spread without any curative treatment available at this stage. These challenges better explain the two main objectives in the creation of a dedicated UM biobank. First, collecting UM samples is essential due to tissue scarcity. Second, large-scale translational research programs based on stored human samples will help to better determine UM pathogenesis with the aim of identifying new biomarkers, allowing for early diagnosis and new targeted treatment modalities. Other periocular malignancies, such as conjunctival melanomas or orbital malignancies, also raise specific concerns. In this context, the number of biobanks worldwide dedicated to ocular malignancies is very limited. The aims of this article were (i) to describe the specific challenges raised by a dedicated ocular malignancy biobank, (ii) to report our experience in setting up such a biobank, and (iii) to discuss future perspectives in this field.

RESUMEN

Background: Ovarian cancer (OC) is the deadliest gynecological cancer, often diagnosed at advanced stages. A fast and accurate diagnostic method for early-stage OC is needed. The tumor marker gangliosides, GD2 and GD3, exhibit properties that make them ideal potential diagnostic biomarkers, but they have never before been quantified in OC. We investigated the diagnostic utility of GD2 and GD3 for diagnosis of all subtypes and stages of OC. Methods: This retrospective study evaluated GD2 and GD3 expression in biobanked tissue and serum samples from patients with invasive epithelial OC, healthy donors, non-malignant gynecological conditions, and other cancers. GD2 and GD3 levels were evaluated in tissue samples by immunohistochemistry (n=299) and in two cohorts of serum samples by quantitative ELISA. A discovery cohort (n=379) showed feasibility of GD2 and GD3 quantitative ELISA for diagnosing OC, and a subsequent model cohort (n=200) was used to train and cross-validate a diagnostic model. Results: GD2 and GD3 were expressed in tissues of all OC subtypes and FIGO stages but not in surrounding healthy tissue or other controls. In serum, GD2 and GD3 were elevated in patients with OC. A diagnostic model that included serum levels of GD2+GD3+age was superior to the standard of care (CA125, p<0.001) in diagnosing OC and early-stage (I/II) OC. Conclusion: GD2 and GD3 expression was associated with high rates of selectivity and specificity for OC. A diagnostic model combining GD2 and GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early stage. Further research exploring the utility of GD2 and GD3 for diagnosis of OC is warranted.