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1.
Biomaterials ; 313: 122776, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39236629

RESUMEN

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.


Asunto(s)
Células Dendríticas , Hidrogeles , Melanoma , Cicatrización de Heridas , Hidrogeles/química , Animales , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Melanoma/terapia , Melanoma/patología , Cicatrización de Heridas/efectos de los fármacos , Humanos , Recurrencia Local de Neoplasia/prevención & control , Ratones Endogámicos C57BL , Antiinfecciosos/uso terapéutico , Antiinfecciosos/farmacología , Ratones , Línea Celular Tumoral , Femenino
2.
Ceska Gynekol ; 89(4): 309-318, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39242207

RESUMEN

OBJECTIVE: A comprehensive overview of surgical treatment of recurrent gynecological malignancies. Recurrent breast malignancies are not included in this review. METHODOLOGY: A review providing overview of surgical treatment options for recurrent malignancies of adnexa of the uterus (ovary, fallopian tube), uterine corpus, uterine cervix, and carcinoma of the vagina and vulva. CONCLUSION: Optimal surgical treatment for patients with recurrent cancer is based on multidisciplinary approach with stratification according to individual prognostic markers. These include patient's performance status, outcome of primary surgery, current extent of recurrence, and histopathological, molecular, and biochemical characteristics. Decision about choice of treatment should be individually discussed and evaluated by the multidisciplinary oncogynecological commission board.


Asunto(s)
Neoplasias de los Genitales Femeninos , Recurrencia Local de Neoplasia , Humanos , Femenino , Recurrencia Local de Neoplasia/cirugía , Neoplasias de los Genitales Femeninos/cirugía , Neoplasias de los Genitales Femeninos/patología , Procedimientos Quirúrgicos Ginecológicos/métodos
3.
AAPS PharmSciTech ; 25(7): 211, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39242397

RESUMEN

Pirarubicin attracted considerable attention in clinical studies because of its high therapeutic efficacy and reduced toxicity in comparison with other anthracyclines. Nevertheless, ~ 30% patients undergoing PIRA treatment still experience relapse and metastasis. Clinical advancements unveiled that cancer stem cells (CSCs) residing in the tumor constitutes a major factor for such limitations and subsequently are the reason for treatment failure. Consequently, eradicating CSCs alongside bulk tumor is a crucial undertaking to attain utmost therapeutic efficacy of the treatment. Nevertheless, majority of the CSCs inhibitors currently under examination lack specificity, show unsynchronized bioavailability with other primary treatments and exhibit notable toxicity in their therapeutic applications, which is primarily attributable to their inadequate tumor-targeting capabilities. Therefore, we have developed a biodegradable polylactic acid based blend block copolymeric NPs for concomitant delivery of CSCs inhibitor Salinomycin (SAL) & chemotherapeutic drug Pirarubicin (PIRA) with an aim to improve the efficacy of treatment and prevent cancer relapse. Prepared NPs showed < 100 nm size and excellent loading with sustained release for both the drugs. Also, PIRA:SAL co-loaded NPs exhibits synergistically enhanced cytotoxicity against cancer cell as well as CSCs. Most importantly, NPs mediated co-delivery of the drugs showed complete tumor eradication, without any reoccurrence throughout the surveillance period. Additionally, NPs treatment didn't show any histopathological alteration in vital organs confirming their non-toxic nature. Altogether, present study concludes that the developed PIRA:SAL NPs have excellent efficacy for tumor regression as well as prevention of cancer relapse, hence can be used as a potential combination therapy for cancer treatment.


Asunto(s)
Doxorrubicina , Piranos , Piranos/administración & dosificación , Piranos/farmacología , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacología , Humanos , Animales , Línea Celular Tumoral , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Nanopartículas/química , Sinergismo Farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Ratones , Poliésteres/química , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Femenino , Liberación de Fármacos , Policétidos Poliéteres
4.
Pharmacoepidemiol Drug Saf ; 33(9): e70001, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39252433

RESUMEN

PURPOSE: This retrospective real-world study compared overall survival (OS) between patients with BRCA wild-type (BRCAwt) recurrent epithelial ovarian cancer (OC) who received niraparib second-line maintenance (2LM) versus active surveillance (AS) using target trial emulation, cloning, inverse probability of censoring weighting (IPCW) methodology to minimize immortal time bias. METHODS: Eligible patients from a United States-based, deidentified, electronic health record-derived database were diagnosed with epithelial OC (January 1, 2011-May 31, 2021), were BRCAwt, and completed second-line (2L) therapy (January 1, 2017-March 2, 2022). Patient data were cloned at index (2L last treatment date), assigned to niraparib 2LM and AS cohorts, and censored when treatment deviated from clone assignment. Follow-up was measured from index to earliest of study end (May 31, 2022), last activity, or death. Median OS (mOS) and hazard ratios were estimated from stabilized IPCW Kaplan-Meier curves and Cox regression models. RESULTS: Overall, 199 patients received niraparib 2LM, and 707 had their care managed with AS. Key characteristics were balanced across cohorts after cloning and stabilized IPCW. Median follow-up was 15.6- and 9.3-months pre-cloning. IPCW mOS was 24.1 months (95% CI: 20.9-29.5) and 18.4 months (95% CI: 15.1-22.8) in niraparib 2LM and AS cohorts, respectively (hazard ratio, 0.77; 95% CI: 0.66-0.89). CONCLUSIONS: This real-world study provides supportive evidence of an OS benefit for patients with BRCAwt recurrent OC who received 2LM niraparib monotherapy compared with those whose care was managed with AS. The analytic strategies implemented were useful in minimizing immortal time bias and measured confounding.


Asunto(s)
Indazoles , Recurrencia Local de Neoplasia , Neoplasias Ováricas , Piperidinas , Humanos , Femenino , Piperidinas/uso terapéutico , Piperidinas/administración & dosificación , Indazoles/uso terapéutico , Indazoles/administración & dosificación , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/mortalidad , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Adulto , Espera Vigilante , Estados Unidos/epidemiología , Quimioterapia de Mantención/métodos , Bases de Datos Factuales
5.
Arch Esp Urol ; 77(7): 718-725, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39238294

RESUMEN

BACKGROUND: Prostate cancer (PCa) remains a significant global health issue, exhibiting a spectrum of clinical behaviours from indolent to aggressive. Biomarkers are crucial for risk assessment, treatment selection and prognosis prediction. Despite their importance, accurately evaluating PCa aggressiveness and guiding personalised treatment strategies present challenges. This review aims to evaluate biomarkers for assessing recurrence risk following radical prostatectomy, with a focus on personalised follow-up and timely intervention for high-risk patients. This review assesses the clinical significance of immunohistochemical biomarkers, including LIM domain kinase 1 (LIMK1), Antigen Kiel 67 (Ki67), PTEN and ERG, in PCa management. A comprehensive literature review examined the correlation between these biomarkers and biochemical recurrence (BCR) in patients undergoing radical prostatectomy. Our search included articles published between 2019 and 2024, yielding 87 articles, with 7 focused on the correlation between LIMK1 and BCR, 46 on Ki67 and 34 on PTEN/ERG biomarkers. After applying the exclusion criteria, 36 articles were included for review. LIMK1, a serine/threonine kinase, is highly expressed in cancers like PCa. It influences cell survival and motility through actin cytoskeleton reorganisation, correlating with poor prognosis, aggressive tumour behaviour and BCR. Similarly, Ki67, a marker of cell proliferation, predicts high-risk PCa and worse prognosis, particularly in castration-resistant cases, although its association with recurrence risk remains debated. PTEN loss and ERG fusion are prevalent genetic alterations in PCa, with PTEN loss linked to poor prognosis and ERG fusion associated with increased disease progression and BCR post-prostatectomy. Integrating these biomarkers into clinical practice can enhance risk stratification and inform personalised treatment strategies for patients with PCa. Despite promising findings, further validation studies and standardisation of detection methods are needed to ensure the clinical utility of these biomarkers. Continued research is essential to validate and optimise the clinical utility of these biomarkers, paving the way for more effective PCa management strategies and improved patient outcomes and quality of life.


Asunto(s)
Biomarcadores de Tumor , Inmunohistoquímica , Recurrencia Local de Neoplasia , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Medición de Riesgo , Valor Predictivo de las Pruebas
6.
Technol Cancer Res Treat ; 23: 15330338241264843, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39238290

RESUMEN

BACKGROUND: Radical mastectomy remains the cornerstone procedure for the treatment of breast cancer (BC). However, traditional radical surgeries often lead to complications such as local numbness, pulling sensations, and atrophy of the pectoralis major muscle. In contrast, BC radical surgeries that preserve more tissue have shown potential in reducing these complications. This retrospective study aims to analyze case data from our institution, focusing on the methods of surgeries that preserve more tissue and evaluating the safety and reliability of the follow-up results. METHODS: A retrospective observational study was conducted on cases diagnosed with BC between May 2018 and July 2019 at our institution. The cases were divided into three different surgical groups and followed up for a period of 5 years. The follow-up results were then discussed within each group. RESULTS: A total of 315 cases diagnosed with BC underwent regular follow-ups. The statistical analysis revealed an average age of 45 years and an average tumor size slightly over 2.2 cm, with early-stage BC (Stage I and II) accounting for 90.2% of the cases. The overall survival (OS) and disease-free survival times in the group undergoing total mastectomy with tissue preservation were comparable to those in the traditional radical mastectomy group and the breast-conserving plus radiotherapy group. Moreover, the complication rate, particularly the incidence of chest wall numbness and pulling sensations, was lower in the total mastectomy with tissue preservation group compared to the traditional radical mastectomy group. The overall average follow-up time was 64.4 months, with a recurrence and metastasis rate of 15.6% and an OS rate of 92.7%. CONCLUSION: Based on our follow-up results, total mastectomy with more tissue preservation demonstrates comparable efficacy to breast-conserving surgery and traditional radical mastectomy. It can reduce some complications associated with traditional radical mastectomy and is beneficial for subsequent immediate and delayed breast reconstruction. This approach may be suitable for most patients with early to mid-stage breast cancer who do not wish to undergo breast-conserving surgery.


Asunto(s)
Neoplasias de la Mama , Recurrencia Local de Neoplasia , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Adulto , Tejido Subcutáneo/patología , Tejido Subcutáneo/cirugía , Mastectomía/métodos , Estudios de Seguimiento , Anciano , Estadificación de Neoplasias
7.
BJS Open ; 8(5)2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39240223

RESUMEN

BACKGROUND: Radiotherapy reduces local recurrence in locally advanced rectal cancer, but may cause harm in patients who do not experience recurrence. The aim was to investigate the impact of radiotherapy on long-term quality of life after curative treatment for rectal cancer, i.e. in patients without a recurrence during the follow-up. METHODS: All patients operated on for rectal cancer in Norway under 75 years of age between 30 September 2007 and 1 October 2020 were identified using the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence and dementia. The primary outcome measure was the Gastrointestinal Quality of Life Index. Secondary outcome measures included the 36-item Short Form Survey. Inverse probability weights based on a multiple logistic regression model were used to balance prechosen covariates between the radiotherapy and no radiotherapy groups when assessing differences in outcomes. RESULTS: Of 5014 invited patients, 2142 (43%) eligible patients answered the questionnaires. Of these 762 (36%) were treated with neoadjuvant radiotherapy plus surgery and 1380 (64%) with surgery alone. The mean follow-up time was 6.4 and 7.4 years respectively. After propensity score matching, the Gastrointestinal Quality of Life Index differed significantly between irradiated and non-irradiated patients ((mean(s.d.), mean score 103.8(19.4) versus 110.8(19.6) respectively, mean difference: -6.96 (95% c.i. -8.72 to -5.19); P < 0.001). Among patients without a stoma the mean difference was -8.1 points, whereas it was -5.7 for patients with a stoma. The radiotherapy group also scored significantly lower in 7 of 8 36-item Short Form Survey domains compared with the surgery alone group. CONCLUSION: Long-term quality of life was significantly lower in patients without a recurrence during the follow-up who received radiotherapy compared with patients who did not. These findings warrant a critical re-evaluation of the use of radiotherapy both in traditional neoadjuvant treatment and in modern organ-preserving treatment regimens.


Asunto(s)
Calidad de Vida , Neoplasias del Recto , Sistema de Registros , Humanos , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Masculino , Femenino , Persona de Mediana Edad , Noruega , Anciano , Supervivientes de Cáncer/psicología , Supervivientes de Cáncer/estadística & datos numéricos , Recurrencia Local de Neoplasia , Encuestas y Cuestionarios , Estudios de Cohortes , Terapia Neoadyuvante , Adulto , Puntaje de Propensión
8.
PLoS One ; 19(9): e0309834, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39240836

RESUMEN

BACKGROUND: Prognostic implications of peritoneal washing cytology (CY) in patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing surgical resection following preoperative chemoradiotherapy (CRT) remain unclear. This study aimed to elucidate the prognostic significance and predictors of a positive CY status (CY+) after preoperative CRT. METHODS: Clinical data from 141 patients with localized PDAC who underwent curative-intent resection after preoperative CRT were retrospectively analyzed to examine the association between CY+ and clinicopathological factors and survival. RESULTS: CY+ was observed in six patients (4.3%). The CY+ group exhibited significantly higher preoperative serum levels of CA19-9 and a substantially greater incidence of tumor location in the pancreatic body or tail, along with pathological invasion to the anterior pancreatic capsule, than the CY- group. The CY+ group had a significantly higher incidence of peritoneal recurrence compared with the CY- group (83.3% vs. 18.5%, p = 0.002). Overall survival (OS) and recurrence-free survival (RFS) after surgery were significantly shorter in the CY+ group than in the CY- group (CY+ vs. CY-: 18.3 vs. 46.2 months, p = 0.001, and 8.9 vs. 17.7 months, p = 0.009, respectively). Multivariate analyses identified CY+ as an independent prognostic factor for worse OS (hazard ratio 5.00, 95% confidence interval 1.03-12.31) and RFS (hazard ratio 2.58, 95% confidence interval 1.04-6.43). Local invasion grade on imaging before CRT, limited histological response to CRT, and absence of adjuvant chemotherapy were independent predictors of worse OS and RFS. CONCLUSION: Despite the relatively low incidence of CY+ after preoperative CRT, it emerged as an independent prognostic factor in patients with localized PDAC undergoing curative-intent resection following preoperative CRT.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Femenino , Masculino , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Anciano , Persona de Mediana Edad , Pronóstico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/cirugía , Estudios Retrospectivos , Quimioradioterapia , Adulto , Anciano de 80 o más Años , Lavado Peritoneal/métodos , Citodiagnóstico/métodos , Recurrencia Local de Neoplasia/patología , Citología
9.
Cancer Control ; 31: 10732748241280444, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39243163

RESUMEN

Management of recurrent prostate cancer following radiotherapy and subsequent radical prostatectomy poses considerable challenges due to potential complications for patients. Focal therapies have emerged as a burgeoning approach in prostate cancer treatment. Research indicates that ablative therapies exhibit encouraging oncological efficacy while maintaining acceptable functional outcomes in salvage interventions. Here, we present a contemporary review of focal therapy treatment modalities as well as oncologic and functional outcomes.


Asunto(s)
Recurrencia Local de Neoplasia , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Prostatectomía/métodos , Terapia Recuperativa/métodos , Técnicas de Ablación/métodos , Resultado del Tratamiento
10.
World J Surg Oncol ; 22(1): 240, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39244533

RESUMEN

BACKGROUND: Postoperative recurrence is a vital reason for poor 5-year overall survival in hepatocellular carcinoma (HCC) patients. The ADV score is considered a parameter that can quantify HCC aggressiveness. This study aimed to identify HCC patients at high-risk of recurrence early using the ADV score. METHODS: The medical data of consecutive HCC patients undergoing hepatectomy from The First Affiliated Hospital of Nanjing Medical University (TFAHNJMU) and Nanjing Drum Tower Hospital (NJDTH) were retrospectively reviewed. Based on the status of microvascular invasion and the Edmondson-Steiner grade, HCC patients were divided into three groups: low-risk group (group 1: no risk factor exists), medium-risk group (group 2: one risk factor exists), and high-risk group (group 3: coexistence of two risk factors). In the training cohort (TFAHNJMU), the R package nnet was used to establish a multi-categorical unordered logistic regression model based on the ADV score to predict three risk groups. The Welch's T-test was used to compare differences in clinical variables in three predicted risk groups. NJDTH served as an external validation center. At last, the confusion matrix was developed using the R package caret to evaluate the diagnostic performance of the model. RESULTS: 350 and 405 patients from TFAHNJMU and NJDTH were included. HCC patients in different risk groups had significantly different liver function and inflammation levels. Density maps demonstrated that the ADV score could best differentiate between the three risk groups. The probability curve was plotted according to the predicted results of the multi-categorical unordered logistic regression model, and the best cut-off values of the ADV score were as follows: low-risk ≤ 3.4 log, 3.4 log < medium-risk ≤ 5.7 log, and high-risk > 5.7 log. The sensitivities of the ADV score predicting the high-risk group (group 3) were 70.2% (99/141) and 78.8% (63/80) in the training and external validation cohort, respectively. CONCLUSION: The ADV score might become a valuable marker for screening patients at high-risk of HCC recurrence with a cut-off value of 5.7 log, which might help surgeons, pathologists, and HCC patients make appropriate clinical decisions.


Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico , Estudios Retrospectivos , Femenino , Masculino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Estudios de Seguimiento , Pronóstico , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Detección Precoz del Cáncer/métodos , Invasividad Neoplásica , Tasa de Supervivencia , Anciano
11.
Cancer Immunol Immunother ; 73(11): 212, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235612

RESUMEN

Patients with lung cancer have a high incidence of tumor recurrence even after curative surgical resection. Some reports indicated that immunosuppressive cells induced by surgical stress could contribute to tumor recurrence after surgery; however, the underlying mechanisms are not fully understood. In this study, we found that increased postoperative blood monocytes served as a risk factor for tumor recurrence in 192 patients with non-small cell lung cancer (NSCLC). We established the lung cancer recurrent mouse model after tumor resection and showed that the surgical stress immediately increased the level of serum monocyte chemoattractant protein-1 (MCP-1), which subsequently increased blood monocytes. These blood monocytes were rapidly recruited into distant micrometastases and became tumor growth-promoting tumor associated macrophages (TAMs). Furthermore, even after the blood MCP-1 and monocytes decreased enough 72 h after tumor resection, TAMs in micrometastases remained rich because the MCP-1 secreted by micrometastases themselves continued to recruit monocytes around the tumor. Consequently, tumor resection triggered the outgrowth of distant metastases via the MCP-1-Monocyte-TAM axis. When we administered the MCP-1 inhibitor to the lung cancer recurrent model mice, blood monocytes decreased after tumor resection, and TAMs in micrometastases also dramatically decreased. Finally, peri- and postoperative treatment with the MCP-1 inhibitor suppressed distant metastases after surgery. Targeting the MCP-1-Monocyte-TAM axis may inhibit surgical stress-induced NSCLC recurrence by attenuating postoperative immunosuppressive monocytes in micrometastases.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Quimiocina CCL2 , Neoplasias Pulmonares , Monocitos , Recurrencia Local de Neoplasia , Animales , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Monocitos/inmunología , Monocitos/metabolismo , Ratones , Humanos , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Masculino , Femenino , Quimiocina CCL2/metabolismo , Ratones Endogámicos C57BL , Metástasis de la Neoplasia , Persona de Mediana Edad , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Anciano
12.
Cancer Immunol Immunother ; 73(11): 223, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235656

RESUMEN

BACKGROUND: To assess the distribution characteristics of immune infiltration and lymphovascular invasion in breast cancer skin recurrence patients. METHODS: We retrospectively analyzed the clinicopathological data of patients who underwent radical surgery for primary breast cancer and experienced skin recurrence between January 2001 and April 2019. Immune and lymphovascular biomarkers were quantified in primary breast cancers, skin lesions and visceral metastatic lesions. Differences in biomarkers distribution between matched tissues were statistically analyzed using the Wilcoxon signed-rank test and Kruskal-Wallis one-way ANOVA. RESULTS: A total of 71 female breast cancer patients were reviewed in this study. Our study found that the expression levels of various lymphocyte immune markers in primary tumor specimens were higher than those in skin recurrences. The expression of CD8, CD57 and CD31 in primary breast cancer was higher than those in the skin. Compared to visceral metastatic lesions, D2-40 was highly expressed in the skin, while CD8 tended to decrease. In the skin specimens, the expression of CD8 (P < 0.001), FOXP3 (P = 0.006) and CD68 (P < 0.001) in the intratumoral area was higher, while the expression of CD57 (P < 0.001) was higher in the peritumoral area. Analyzing specimens from the same patient at different time points of skin progression, it was found that the expression of peritumoral CD4 decreased (P = 0.044) as the disease progressed. The low expression of D2-40 and CD163 in the skin lesions suggested a decrease in DFS. CONCLUSION: The immune microenvironment of breast cancer skin recurrence may be in a state of suppression, and this suppression may intensify with disease progression. The pattern of skin recurrence may be more inclined toward lymphatic invasion. Our study provides new insights into the biological behaviors of this disease and its response to immunotherapy.


Asunto(s)
Neoplasias de la Mama , Linfocitos Infiltrantes de Tumor , Recurrencia Local de Neoplasia , Neoplasias Cutáneas , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/metabolismo , Anciano , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Adulto , Metástasis Linfática/patología , Metástasis Linfática/inmunología , Biomarcadores de Tumor/metabolismo , Microambiente Tumoral/inmunología , Invasividad Neoplásica , Pronóstico
13.
BMC Cancer ; 24(1): 1106, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237882

RESUMEN

BACKGROUND: This study aims to investigate preoperative prognostic factors available for intrahepatic cholangiocarcinoma (ICC) patients and propose a new preoperative prognostic scoring system for ICC that combines CA19-9 and neutrophil/lymphocyte ratio (NLR). METHODS: In this retrospective analysis, 1728 patients diagnosed with ICC and undergoing curative liver resections were studied. This study employed univariate and multivariate Cox regression to find factors affecting recurrence and overall survival (OS), and furthermore assessed how preoperative models influenced tumor traits and postoperative recurrence. RESULTS: The results of the multivariate Cox regression analysis indicated that two preoperative variables, NLR and Ca19-9, were independent risk factors affecting postoperative recurrence and OS in ICC patients. Based on this data, assigning a score of 0 (NLR ≤ 2.4 and Ca19-9 ≤ 37U/ml) or 1 (NLR > 2.4 and Ca19-9 > 37U/ml) to these two factors, a preoperative prognostic score was derived. According to the scoring model, patients were divided into three groups: 0 points (low-risk group), 1 point (intermediate-risk group), and 2 points (high-risk group). The 5-year recurrence and OS rates for the three groups were 56.6%, 68.2%, 77.8%, and 56.8%, 40.6%, 27.6%, respectively, with all P values < 0.001. Furthermore, high-risk group patients were more prone to early recurrence (early recurrence rates for high-, intermediate-, and low-risk groups were 56.8%, 51.5%, and 37.1%, respectively, P < 0.001) and extrahepatic metastasis (extrahepatic metastasis rates for high-, intermediate-, and low-risk groups were 31.7%, 26.4%, and 15.4%, respectively, P < 0.001). In terms of tumor characteristics, high-risk group patients had larger tumor diameters and were more likely to experience microvascular invasion, lymph node metastasis, and perineural invasion. CONCLUSIONS: The predictive capacity of postoperative recurrence and OS rates in ICC patients is effectively captured by the preoperative scoring system incorporating NLR and CA19-9 levels.


Asunto(s)
Neoplasias de los Conductos Biliares , Antígeno CA-19-9 , Colangiocarcinoma , Hepatectomía , Linfocitos , Recurrencia Local de Neoplasia , Neutrófilos , Humanos , Colangiocarcinoma/cirugía , Colangiocarcinoma/sangre , Colangiocarcinoma/patología , Colangiocarcinoma/mortalidad , Masculino , Femenino , Neutrófilos/patología , Persona de Mediana Edad , Pronóstico , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/sangre , Neoplasias de los Conductos Biliares/mortalidad , Estudios Retrospectivos , Linfocitos/patología , Antígeno CA-19-9/sangre , Anciano , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Adulto , Periodo Preoperatorio , Recuento de Linfocitos , Factores de Riesgo
14.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(4): 807-817, 2024 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-39218608

RESUMEN

High-grade serous ovarian cancer has a high degree of malignancy, and at detection, it is prone to infiltration of surrounding soft tissues, as well as metastasis to the peritoneum and lymph nodes, peritoneal seeding, and distant metastasis. Whether recurrence occurs becomes an important reference for surgical planning and treatment methods for this disease. Current recurrence prediction models do not consider the potential pathological relationships between internal tissues of the entire ovary. They use convolutional neural networks to extract local region features for judgment, but the accuracy is low, and the cost is high. To address this issue, this paper proposes a new lightweight deep learning algorithm model for predicting recurrence of high-grade serous ovarian cancer. The model first uses ghost convolution (Ghost Conv) and coordinate attention (CA) to establish ghost counter residual (SCblock) modules to extract local feature information from images. Then, it captures global information and integrates multi-level information through proposed layered fusion Transformer (STblock) modules to enhance interaction between different layers. The Transformer module unfolds the feature map to compute corresponding region blocks, then folds it back to reduce computational cost. Finally, each STblock module fuses deep and shallow layer depth information and incorporates patient's clinical metadata for recurrence prediction. Experimental results show that compared to the mainstream lightweight mobile visual Transformer (MobileViT) network, the proposed slicer visual Transformer (SlicerViT) network improves accuracy, precision, sensitivity, and F1 score, with only 1/6 of the computational cost and half the parameter count. This research confirms that the proposed algorithm model is more accurate and efficient in predicting recurrence of high-grade serous ovarian cancer. In the future, it can serve as an auxiliary diagnostic technique to improve patient survival rates and facilitate the application of the model in embedded devices.


Asunto(s)
Algoritmos , Aprendizaje Profundo , Recurrencia Local de Neoplasia , Redes Neurales de la Computación , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/patología , Metadatos , Cistadenocarcinoma Seroso/patología
15.
Cancer Discov ; 14(9): 1574-1576, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39228296

RESUMEN

Juvenile myelomonocytic leukemia (JMML) is a rare pediatric hematologic malignancy with a high relapse rate and a poor prognosis hallmarked by RAS pathway mutations. Stieglitz and colleagues conducted a phase II clinical trial using the MEK inhibitor trametinib to treat patients with relapsed and refractory juvenile myelomonocytic leukemia and observed an objective response rate of 50% and an overall survival of 80% after 4 years. See related article by Stieglitz et al., p. 1590 (4) .


Asunto(s)
Leucemia Mielomonocítica Juvenil , Piridonas , Pirimidinonas , Humanos , Piridonas/uso terapéutico , Pirimidinonas/uso terapéutico , Leucemia Mielomonocítica Juvenil/tratamiento farmacológico , Leucemia Mielomonocítica Juvenil/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Ensayos Clínicos Fase II como Asunto , Recurrencia Local de Neoplasia/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Resultado del Tratamiento , Enfermedades Raras/tratamiento farmacológico , Ensayos Clínicos como Asunto
17.
Can J Urol ; 31(4): 11931-11940, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39217516

RESUMEN

INTRODUCTION:   Prostate cancer has a variable natural history and, despite the existence of biochemical recurrence (BCR) predictors, they are still limited in predicting outcomes.  The role of testosterone in advanced prostate cancer is well known, however its role in localized prostate cancer is still uncertain.  In the present study, we evaluated the relationship of testosterone levels and androgen receptor (AR) expression with oncological and functional outcomes, in patients undergoing radical retropubic prostatectomy (RRP). MATERIALS AND METHODS:   Through a retrospective study, patients who underwent RRP, who had at least two preoperative total testosterone dosages, were analyzed and compared according to testosterone levels, oncological and functional outcomes.  After analyzing data, tissue samples were selected in a biorepository to carry out the AR and the AR-V7 expression. RESULTS:   After applying exclusion criteria, 212 patients were included in the analysis.  Thirty-two patients (15.1%) had low testosterone levels and, in this group, a lower rates of erectile function recovery were observed at 24 months (53.1% vs. 71.7%; p = 0.037), a higher rate of BCR (21.9% vs. 9.4%; p = 0.041) and higher International Society of Urological Pathology (ISUP) grade in biopsy products.  The AR expression was higher in patients with low testosterone, but there was no difference in relapse rates. CONCLUSIONS:   Lower levels of testosterone were related to lower rates of erectile function recovery at the end of 24 months after RRP, in addition to conferring higher rates of BCR and higher ISUP grades in biopsy.  Furthermore, patients with total testosterone < 300 ng/dL had higher expression of AR, but no difference in BCR rates.


Asunto(s)
Prostatectomía , Neoplasias de la Próstata , Receptores Androgénicos , Testosterona , Humanos , Masculino , Prostatectomía/métodos , Testosterona/sangre , Receptores Androgénicos/metabolismo , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Recurrencia Local de Neoplasia
18.
Sci Rep ; 14(1): 21607, 2024 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-39284867

RESUMEN

This paper aims to analyze the risk factors for the recurrence or progression of non-functioning pituitary adenomas (NFPAs) in male patients after transnasal sphenoidal surgery and to develop a predictive model for prognosis. Clinical and follow-up data of 126 male patients with NFPAs treated by transnasal sphenoidal surgery from January 2011 to January 2021 in Fuzhou 900th Hospital were retrospectively analyzed. Lasso regression analysis was used to screen the best predictors, and the predictors were further screened by multivariate logistic regression analysis, and the nomogram prediction model was constructed. The performance of the model was verified by three aspects: discrimination, calibration and clinical utility by using the consistency index (C-index), receiver operating characteristic curve (ROC), calibration curve, clinical decision curve (DCA) and Clinical impact curve (CIC). Out of 126 cases, 7 (5.56%) showed postoperative tumor recurrence, and 18 (14.29%) exhibited postoperative residual regrowth (progression). Age (P = 0.024), maximum tumor diameter (P < 0.001), modified Knosp grade (P < 0.001), resection extent (P < 0.001), Ki67 (P < 0.001), pressure symptom (P < 0.001), Pre-op hypopituitarism (P = 0.048), Post-op new hypopituitarism (P = 0.017) showed significant differences among the recurrence group, the progression group, and the alleviation group. Three independent risk factors (Ki67, modified Knosp grade, and resection extent) affecting postoperative remission were used to construct a predictive model for long-term postoperative failure to remit. The C-index of the nomogram model was 0.823, suggesting that the model had a high discriminatory power, and the AUC of the area under the ROC curve was 0.9[95% CI (0.843, 0.958)]. A nomogram prediction model based on modified Knosp grading (grades 3B-4), resection extent (partial resection), and Ki-67 (≥ 3%) predicts the recurrence or progression of NFPAs in men after transnasal sphenoidal surgery.


Asunto(s)
Adenoma , Progresión de la Enfermedad , Recurrencia Local de Neoplasia , Nomogramas , Neoplasias Hipofisarias , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Factores de Riesgo , Adulto , Adenoma/cirugía , Adenoma/patología , Estudios Retrospectivos , Anciano , Pronóstico , Curva ROC
19.
PLoS One ; 19(9): e0307815, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39259736

RESUMEN

OBJECTIVE: The purpose of this study was to determine and compare the performance of pre-treatment clinical risk score (CRS), radiomics models based on computed (CT), and their combination for predicting time to recurrence (TTR) and disease-specific survival (DSS) in patients with colorectal cancer liver metastases. METHODS: We retrospectively analyzed a prospectively maintained registry of 241 patients treated with systemic chemotherapy and surgery for colorectal cancer liver metastases. Radiomics features were extracted from baseline, pre-treatment, contrast-enhanced CT images. Multiple aggregation strategies were investigated for cases with multiple metastases. Radiomics signatures were derived using feature selection methods. Random survival forests (RSF) and neural network survival models (DeepSurv) based on radiomics features, alone or combined with CRS, were developed to predict TTR and DSS. Leveraging survival models predictions, classification models were trained to predict TTR within 18 months and DSS within 3 years. Classification performance was assessed with area under the receiver operating characteristic curve (AUC) on the test set. RESULTS: For TTR prediction, the concordance index (95% confidence interval) was 0.57 (0.57-0.57) for CRS, 0.61 (0.60-0.61) for RSF in combination with CRS, and 0.70 (0.68-0.73) for DeepSurv in combination with CRS. For DSS prediction, the concordance index was 0.59 (0.59-0.59) for CRS, 0.57 (0.56-0.57) for RSF in combination with CRS, and 0.60 (0.58-0.61) for DeepSurv in combination with CRS. For TTR classification, the AUC was 0.33 (0.33-0.33) for CRS, 0.77 (0.75-0.78) for radiomics signature alone, and 0.58 (0.57-0.59) for DeepSurv score alone. For DSS classification, the AUC was 0.61 (0.61-0.61) for CRS, 0.57 (0.56-0.57) for radiomics signature, and 0.75 (0.74-0.76) for DeepSurv score alone. CONCLUSION: Radiomics-based survival models outperformed CRS for TTR prediction. More accurate, noninvasive, and early prediction of patient outcome may help reduce exposure to ineffective yet toxic chemotherapy or high-risk major hepatectomies.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/cirugía , Masculino , Femenino , Persona de Mediana Edad , Anciano , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Pronóstico , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Resultado del Tratamiento , Adulto , Radiómica
20.
BMJ ; 386: e079089, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39260879

RESUMEN

OBJECTIVE: To provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023). STUDY SELECTION: Included studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions). DATA EXTRACTION: Two independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively. DATA SYNTHESIS: Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran's Q test and I2 statistic. Network meta-analysis was used to integrate all available evidence. MAIN OUTCOME MEASURES: The pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics. RESULTS: From 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF. CONCLUSIONS: MHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023460249.


Asunto(s)
Neoplasias de la Mama , Fraccionamiento de la Dosis de Radiación , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Neoplasias de la Mama/radioterapia , Femenino , Recurrencia Local de Neoplasia
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