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International Journal of Surgery... Jun 2024Breast cancer (BC) is the most common cancer among women worldwide, with 2.3 million new cases and 685,000 deaths annually. It has the highest incidence in North...
BACKGROUND
Breast cancer (BC) is the most common cancer among women worldwide, with 2.3 million new cases and 685,000 deaths annually. It has the highest incidence in North America, Europe, and Australia and lower rates in parts of Asia and Africa. Risk factors include age, family history, hormone replacement therapy, obesity, alcohol consumption, and lack of physical activity. BRCA1 and BRCA2 gene mutations significantly increase the risk. The five-year survival rate is over 90% in developed countries but lower in developing ones. Early screening and diagnosis, using mammography and MRI, are crucial for reducing mortality. In recent years, significant progress has been made in studying BC immunophenotyping, particularly in multicolor flow cytometry, molecular imaging techniques, and tumor microenvironment analysis. These technologies improve diagnosis, classification, and detection of minimal residual disease. Novel immunotherapies targeting the tumor microenvironment, like CAR-T cell therapy, show high efficiency and fewer side effects. High levels of tumor-infiltrating lymphocytes (TILs) correlate with better prognosis, while immune checkpoint molecules (PD-1, PD-L1) help cancer cells evade the immune system. Tumor-associated macrophages (TAMs) promote invasion and metastasis. Blocking molecules like CTLA-4, LAG-3, and TIM-3 enhance anti-tumor responses, and cytokines like IL-10 and TGF-β aid tumor growth and immune evasion. Mendelian randomization (MR) studies use genetic variants to reduce confounding bias and avoid reverse causation, providing robust causal inferences about immune cell phenotypes and BC. This approach supports the development of precision medicine and personalized treatment strategies for BC.
METHODS
This study aims to conduct Mendelian Randomization (MR) analysis on 731 immune cell phenotypes with BC in the BCAC and Finngen R10 datasets, followed by a meta-analysis of the primary results using the inverse-variance weighted (IVW) method and multiple corrections for the significance p values from the meta-analysis. Specifically, the study is divided into three parts: First, data on 731 immune cell phenotypes and BC are obtained and preprocessed from the GWAS Catalog and Open GWAS (BCAC) and the Finngen R10 databases. Second, MR analysis is performed on the 731 immune cell phenotypes with BC data from the BCAC and Finngen R10 databases, followed by a meta-analysis of the primary results using the IVW method, with multiple corrections for the significance p values from the meta-analysis. Finally, the positively identified immune cell phenotypes are used as outcome variables, and BC as the exposure variable for reverse MR validation.
RESULTS
The study found that two immune phenotypes exhibited strong significant associations in MR analysis combined with meta-analysis and multiple corrections. For the immune phenotype CD3 on CD28+ CD4-CD8- T cells, the results were as follows: In the BCAC dataset, the IVW result was Odds Ratio (OR) = 0.942 (95% confidence interval (CI) = 0.915 ~ 0.970, P = 6.76 × 10-5), β = -0.059; MR Egger result was β = -0.095; and the weighted median result was β = -0.060. In the Finngen R10 dataset, the IVW result was OR = 0.956 (95% CI = 0.907 ~ 1.01, P = 0.092), β = -0.045; MR Egger result was β = -0.070; and weighted median result was β = -0.035. The β values were consistent in direction across all three MR methods in both datasets. The meta-analysis of the IVW results from both datasets showed OR = 0.945 (95% CI = 0.922 ~ 0.970, P = 1.70 × 10-5). After Bonferroni correction, the significant P-value was P = 0.01, confirming the immune phenotype as a protective factor against BC. For the immune phenotype HLA DR on CD33- HLA DR+, the results were as follows: In the BCAC dataset, the IVW result was OR = 0.977 (95% CI = 0.964 ~ 0.990, P = 7.64 × 10-4), β = -0.023; MR Egger result was β = -0.016; and the weighted median result was β = -0.019. In the Finngen R10 dataset, the IVW result was OR = 0.960 (95% CI = 0.938 ~ 0.983, P = 6.51 × 10-4), β = -0.041; MR Egger result was β = -0.064; and weighted median result was β = -0.058. The β values were consistent in direction across all three MR methods in both datasets. The meta-analysis of the IVW results from both datasets showed OR = 0.973 (95% CI = 0.961 ~ 0.984, P = 3.80 × 10-6). After Bonferroni correction, the significant P-value was P = 0.003, confirming this immune phenotype as a protective factor against BC. When the immune cell phenotypes CD3 on CD28+ CD4-CD8- T cells and HLA DR on CD33- HLA DR+ were used as outcomes and BC was used as exposure, the data processing and analysis procedures were the same. The MR analysis results are as follows: Data from the FinnGen database regarding the effect of positive immune phenotypes on malignant neoplasm of the breast indicated a β coefficient of -0.011, OR = 0.99 (95% CI = -0.117 ~ 0.096, P = 0.846); data from the BCAC database regarding favorable immune phenotypes for BC demonstrated a β coefficient of -0.052, OR = 0.095 (95% CI = -0.144 ~ 0.040, P = 0.266). The results suggest insufficient evidence in both databases to indicate that BC inversely affects these two immune cell phenotypes.
CONCLUSIONS
Evidence suggests that the immune cell phenotypes CD3 on CD28+ CD4-CD8- T cells and HLA DR on CD33- HLA DR+ protect against BC. This protective effect may be achieved through various mechanisms, including enhancing immune surveillance to recognize and eliminate tumor cells; secreting cytokines to inhibit tumor cell proliferation and growth directly; triggering apoptotic pathways in tumor cells to reduce their number; modulating the tumor microenvironment to make it unfavorable for tumor growth and spread; activating other immune cells to boost the overall immune response; and inhibiting angiogenesis to reduce the tumor's nutrient supply. These mechanisms work together to help protect BC patients and slow disease progression. Both immune cell phenotypes are protective factors for BC patients and can be targeted to enhance their function and related pathways for BC treatment.
PubMed: 38935111
DOI: 10.1097/JS9.0000000000001840 -
Frontiers in Surgery 2024Infrared thermography (IT) is a non-invasive real-time imaging technique with potential application in different areas of neurosurgery. Despite technological advances in...
INTRODUCTION
Infrared thermography (IT) is a non-invasive real-time imaging technique with potential application in different areas of neurosurgery. Despite technological advances in the field, intraoperative IT (IIT) has been an underestimated tool with scarce reports on its usefulness during intracranial tumor resection. We aimed to evaluate the usefulness of high-resolution IIT with static and dynamic thermographic maps for transdural lesion localization, and diagnosis, to assess the extent of resection, and the occurrence of perioperative acute ischemia.
METHODS
In a prospective study, 15 patients affected by intracranial tumors (six gliomas, four meningiomas, and five brain metastases) were examined with a high-resolution thermographic camera after craniotomy, after dural opening, and at the end of tumor resection.
RESULTS
Tumors were transdurally located with 93.3% sensitivity and 100% specificity ( < 0.00001), as well as cortical arteries and veins. Gliomas were consistently hypothermic, while metastases and meningiomas exhibited highly variable thermographic maps on static ( = 0.055) and dynamic ( = 0.015) imaging. Residual tumors revealed non-specific static but characteristic dynamic thermographic maps. Ischemic injuries were significantly hypothermic ( < 0.001).
CONCLUSIONS
High-resolution IIT is a non-invasive alternative intraoperative imaging method for lesion localization, diagnosis, assessing the extent of tumor resection, and identifying acute ischemia changes with static and dynamic thermographic maps.
PubMed: 38933651
DOI: 10.3389/fsurg.2024.1386722 -
Frontiers in Immunology 2024
Topics: Humans; Hematologic Neoplasms; Liquid Biopsy; Biomarkers, Tumor; Neoplastic Cells, Circulating
PubMed: 38933278
DOI: 10.3389/fimmu.2024.1440394 -
Medicina (Kaunas, Lithuania) Jun 2024Hepatocellular carcinoma is the most common primary liver tumor. Orthotopic liver transplant is one of the best treatment options, but its waiting list has to be... (Review)
Review
Hepatocellular carcinoma is the most common primary liver tumor. Orthotopic liver transplant is one of the best treatment options, but its waiting list has to be considered. Bridge therapies have been introduced in order to limit this issue. The aim of this study is to evaluate if bridge therapies in advanced hepatocellular carcinoma can improve overall survival and reduce de-listing. We selected 185 articles. The search was limited to English articles involving only adult patients. These were deduplicated and articles with incomplete text or irrelevant conclusions were excluded. Sorafenib is the standard of care for advanced hepatocellular carcinoma and increases overall survival without any significant drug toxicity. However, its survival benefit is limited. The combination of transarterial chemoembolization + sorafenib, instead, delays tumor progression, although its survival benefit is still uncertain. A few studies have shown that patients undergoing transarterial chemoembolization + radiation therapy have similar or even better outcomes than those undergoing transarterial chemoembolization or sorafenib alone for rates of histopathologic complete response (89% had no residual in the explant). Also, the combined therapy of transarterial chemoembolization + radiotherapy + sorafenib was compared to the association of transarterial chemoembolization + radiotherapy and was associated with a better survival rate (24 vs. 17 months). Moreover, immunotherapy revealed new encouraging perspectives. Combination therapies showed the most encouraging results and could become the gold standard as a bridge to transplant for patients with advanced hepatocellular carcinoma.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Liver Transplantation; Sorafenib; Chemoembolization, Therapeutic; Combined Modality Therapy; Antineoplastic Agents; Bridge Therapy
PubMed: 38929627
DOI: 10.3390/medicina60061010 -
Cancers Jun 2024CtDNA is emerging as a non-invasive clinical detection method for several cancers, including genitourinary (GU) cancers such as prostate cancer, bladder cancer, and... (Review)
Review
CtDNA is emerging as a non-invasive clinical detection method for several cancers, including genitourinary (GU) cancers such as prostate cancer, bladder cancer, and renal cell carcinoma (RCC). CtDNA assays have shown promise in early detection of GU cancers, providing prognostic information, assessing real-time treatment response, and detecting residual disease and relapse. The ease of obtaining a "liquid biopsy" from blood or urine in GU cancers enhances its potential to be used as a biomarker. Interrogating these "liquid biopsies" for ctDNA can then be used to detect common cancer mutations, novel genomic alterations, or epigenetic modifications. CtDNA has undergone investigation in numerous clinical trials, which could address clinical needs in GU cancers, for instance, earlier detection in RCC, therapeutic response prediction in castration-resistant prostate cancer, and monitoring for recurrence in bladder cancers. The utilization of liquid biopsy for ctDNA analysis provides a promising method of advancing precision medicine within the field of GU cancers.
PubMed: 38927984
DOI: 10.3390/cancers16122280 -
Risk of Tumor Progression after Microsurgery for Parasellar Meningioma Invading the Cavernous Sinus.Cancers Jun 2024Parasellar meningiomas, which may invade the cavernous sinus, pose a significant challenge to neurosurgeons due to the high risk of postoperative neurological deficits...
BACKGROUND
Parasellar meningiomas, which may invade the cavernous sinus, pose a significant challenge to neurosurgeons due to the high risk of postoperative neurological deficits associated with aggressive resection of the intracavernous part of the tumour. Therefore, subtotal tumour removal followed by observation or radiotherapy for the residual meningioma in the cavernous sinus is recommended. This retrospective study aimed to identify prognostic factors influencing recurrence and progression-free survival (PFS) in parasellar meningiomas invading the cavernous sinus after incomplete surgical treatment.
METHODS
This study included adult patients diagnosed with benign parasellar meningioma (WHO Grade I) invading the cavernous sinus, treated at our institution between 2006 and 2020, and with a postsurgical follow-up of at least 3 years. Surgical treatment involved near-total resection (NTR) with an intracavernous residual tumour or subtotal resection (STR) with additional extracavernous tumour left in place. Kaplan-Meier analysis estimated PFS rates, and Cox regression tested survival time differences between groups.
RESULTS
Among the 32 patients, the estimated median PFS was 11 years. Radiotherapy improved 5-year PFS only in patients with STR ( = 0.003). The univariate analysis identified preoperative tumour size, low preoperative Karnofsky Performance Score (KPS), and marked brain oedema as significant factors affecting meningioma progression after surgery. The multivariate analysis confirmed tumour size as an independent factor for progression ( = 0.012).
CONCLUSIONS
For patients with parasellar meningioma invading the cavernous sinus, extracavernous tumour removal followed by close radiological surveillance of the residual intracavernous meningioma is a safe and appropriate strategy. When an extracavernous tumour component is left, adjuvant stereotactic radiotherapy or radiosurgery is recommended to control tumour growth.
PubMed: 38927924
DOI: 10.3390/cancers16122217 -
Cancers Jun 2024Hairy-cell leukemia (HCL) is a rare B-cell chronic lymphoproliferative disorder (B-CLPD), whose favorable prognosis has changed with the use of purine nucleoside analogs...
Recommendations for the Management of Patients with Hairy-Cell Leukemia and Hairy-Cell Leukemia-like Disorders: A Work by French-Speaking Experts and French Innovative Leukemia Organization (FILO) Group.
INTRODUCTION
Hairy-cell leukemia (HCL) is a rare B-cell chronic lymphoproliferative disorder (B-CLPD), whose favorable prognosis has changed with the use of purine nucleoside analogs (PNAs), such as cladribine (CDA) or pentostatin (P). However, some patients eventually relapse and over time HCL becomes resistant to chemotherapy. Many discoveries have been made in the pathophysiology of HCL during the last decade, especially in genomics, with the identification of the BRAF mutation and cellular biology, including the importance of signaling pathways as well as tumor microenvironment. All of these new developments led to targeted treatments, especially BRAF inhibitors (BRAFis), MEK inhibitors (MEKis), Bruton's tyrosine kinase (BTK) inhibitors (BTKis) and recombinant anti-CD22 immunoconjugates.
RESULTS
The following major changes or additions were introduced in these updated guidelines: the clinical relevance of the changes in the classification of splenic B-cell lymphomas and leukemias; the increasingly important diagnostic role of BRAF mutation; and the prognostic role of the immunoglobulin (IG) variable (V) heavy chain (H) () mutational status and repertory. We also wish to insist on the specific involvement of bones, skin, brain and/or cerebrospinal fluid (CSF) of the disease at diagnosis or during the follow-up, the novel targeted drugs (BRAFi and MEKi) used for HCL treatment, and the increasing role of minimal residual disease (MRD) assessment.
CONCLUSION
Here we present recommendations for the diagnosis of HCL, treatment in first line and in relapsed/refractory patients as well as for HCL-like disorders including HCL variant (HCL-V)/splenic B-cell lymphomas/leukemias with prominent nucleoli (SBLPN) and splenic diffuse red pulp lymphoma (SDRPL).
PubMed: 38927891
DOI: 10.3390/cancers16122185 -
Neurosurgery Jun 2024Isocitrate dehydrogenase (IDH)-mutant astrocytomas central nervous system World Health Organization grade 2 and 3 show heterogeneous appearance on MRI. In the...
The T1/T2 Ratio is Associated With Resectability in Patients With Isocitrate Dehydrogenase-Mutant Astrocytomas Central Nervous System World Health Organization Grades 2 and 3.
BACKGROUND AND OBJECTIVES
Isocitrate dehydrogenase (IDH)-mutant astrocytomas central nervous system World Health Organization grade 2 and 3 show heterogeneous appearance on MRI. In the premolecular era, the discrepancy between T1 hypointense and T2 hyperintense tumor volume in absolute values has been proposed as a marker for diffuse tumor growth. We set out to investigate if a ratio of T1 to T2 tumor volume (T1/T2 ratio) is associated with resectability and overall survival (OS) in patients with IDH-mutant astrocytomas.
METHODS
Patient data from 2 centers (Sahlgrenska University Hospital, Center A; LMU University Hospital, Center B) were collected retrospectively. Inclusion criteria were as follows: pre and postoperative MRI scans available for volumetric analysis (I), diagnosis of an IDH-mutant astrocytoma between 2003 and 2021 (II), and tumor resection at initial diagnosis (III). Tumor volumes were manually segmented. The T1/T2 ratio was calculated and correlated with extent of resection, residual T2 tumor volume, and OS.
RESULTS
The study comprised 134 patients with 65 patients included from Center A and 69 patients from Center B. The median OS was 134 months and did not differ between the cohorts (P = .29). Overall, the median T1/T2 ratio was 0.79 (range 0.15-1.0). Tumors displaying a T1/T2 ratio of 0.33 or lower showed significantly larger residual tumor volumes postoperatively (median 17.9 cm3 vs 4.6 cm3, P = .03). The median extent of resection in these patients was 65% vs 90% (P = .03). The ratio itself did not correlate with OS. In multivariable analyses, larger postoperative tumor volumes were associated with shorter survival times (hazard ratio 1.02, 95% CI 1.01-1.03, P < .01).
CONCLUSION
The T1/T2 ratio might be a good indicator for diffuse tumor growth on MRI and is associated with resectability in patients with IDH-mutant astrocytoma. This ratio might aid to identify patients in which an oncologically relevant tumor volume reduction cannot be safely achieved.
PubMed: 38920377
DOI: 10.1227/neu.0000000000003069 -
Neurosurgery Practice Mar 2024Gross-total resection (GTR) and low residual tumor volume (RTV) have been associated with increased survival in glioblastoma. Largely due to the subjectivity involved,...
BACKGROUND AND OBJECTIVES
Gross-total resection (GTR) and low residual tumor volume (RTV) have been associated with increased survival in glioblastoma. Largely due to the subjectivity involved, the determination of GTR and RTV remains difficult in the postoperative setting. In response, the objective of this study is to evaluate the clinical efficacy of an easy-to-use MRI metric, called delta T1 (dT1), to quantify extent of resection (EOR) and RTV, in comparison to radiologist impression, to predict overall survival (OS) in glioblastoma patients.
METHODS
59 patients who underwent resection of glioblastoma were retrospectively identified. Delta T1 (dT1) images, automatically created from the difference between calibrated post- and pre-contrast T1-weighted images, were used to quantify EOR and RTV. Kaplan-Meier survival estimates were determined for EOR categories, an RTV cutoff of 5cm and radiologist interpretation of EOR. Multivariate Cox proportional hazard regression analysis was used to evaluate RTV and EOR along with effects related to sex, KPS, MGMT, and age on OS.
RESULTS
Kaplan-Meier analysis revealed a statistically significant difference in median OS for a dT1-determined RTV cutoff of 5 cm (P=.0024, HR=2.18 (1.232-3.856)), but not for radiological impression (P=0.666) or dT1-determined EOR (P=0.0803), which was limited to a comparison between partial and subtotal resections. Furthermore, when covariates were accounted for in multivariate Cox regression, significant differences in OS were retained for dT1-determined RTV. Additionally, a significantly strong yet short-term effect of MGMT methylation status on OS was revealed for each RTV and EOR model.
CONCLUSION
The utility of dT1 maps to quantify EOR and RTV in glioblastoma and predict survival, suggests an emerging role for dT1s with relevance for intraoperative MRI, neuro-navigation and postoperative disease surveillance.
PubMed: 38919518
DOI: No ID Found -
Bulletin Du Cancer Jun 2024Conditioning regimen prior to hematopoietic stem cell transplantation have an impact on patient fertility through the use of gonadal irradiation and/or bifunctional...
Conditioning regimen prior to hematopoietic stem cell transplantation have an impact on patient fertility through the use of gonadal irradiation and/or bifunctional alkylating agents. Their impact on fertility depends mainly on the dose used and, in women, on age at the time of treatment. All patients should benefit before treatment from a consultation informing them of the potential impact on fertility and of fertility preservation techniques. In the absence of contraindications, the major toxicity of myeloablative conditioning regimen justifies fertility preservation. There are few data concerning fertility after reduced-intensity conditioning. Despite lower theoretical gonadotoxicity, we also recommend fertility preservation, if possible before transplantation. The fertility preservation techniques used depend on the patient's age, pathology and conditioning. In the event of subsequent use of harvested gonadal tissue in the context of acute leukemia or aggressive lymphoma, it is advisable to assess the risk of reintroduction of tumor cells. Finally, it is recommended to assess gonadal function after transplant, especially after reduced conditioning. If there is persistent residual gonadal function, post-treatment fertility preservation should be discuss.
PubMed: 38918137
DOI: 10.1016/j.bulcan.2024.04.009