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1.
Cell Metab ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38729152

RESUMEN

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2-expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches, while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs.

2.
Eur J Surg Oncol ; 50(6): 108050, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38498966

RESUMEN

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

3.
Sci Immunol ; 9(92): eadg7995, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38306416

RESUMEN

Adoptive cell therapy (ACT) using ex vivo-expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell-intrinsic immunogenicity and mutational burden. Compared with nonresponders, CD8+ TILs exhibited increased cytotoxicity, exhaustion, and costimulation, whereas myeloid cells had increased type I interferon signaling in responders. Cell-cell interaction prediction analyses corroborated by spatial neighborhood analyses revealed that responders had rich baseline intratumoral and stromal tumor-reactive T cell networks with activated myeloid populations. Successful TIL-ACT therapy further reprogrammed the myeloid compartment and increased TIL-myeloid networks. Our systematic target discovery study identifies potential T-myeloid cell network-based biomarkers that could improve patient selection and guide the design of ACT clinical trials.


Asunto(s)
Inmunoterapia Adoptiva , Melanoma , Humanos , Melanoma/genética , Linfocitos Infiltrantes de Tumor/metabolismo , Proteómica , Linfocitos T CD8-positivos/metabolismo , Microambiente Tumoral
4.
Am J Transplant ; 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38042413

RESUMEN

Surgical site infections (SSIs) are common health care-associated infections. SSIs after kidney transplantation (K-Tx) can endanger patient and allograft survival. Multicenter studies on this early posttransplant complication are scarce. We analyzed consecutive adult K-Tx recipients enrolled in the Swiss Transplant Cohort Study who received a K-Tx between May 2008 and September 2020. All data were prospectively collected with the exception of the categorization of SSI which was performed retrospectively according to the Centers for Disease Control and Prevention criteria. A total of 58 out of 3059 (1.9%) K-Tx recipients were affected by SSIs. Deep incisional (15, 25.9%) and organ/space infections (34, 58.6%) predominated. In the majority of SSIs (52, 89.6%), bacteria were detected, most frequently Escherichia coli (15, 28.9%), Enterococcus spp. (14, 26.9%), and coagulase-negative staphylococci (13, 25.0%). A BMI ≥25 kg/m2 (multivariable OR 2.16, 95% CI 1.07-4.34, P = .023) and delayed graft function (multivariable OR 2.88, 95% CI 1.56-5.34, P = .001) were independent risk factors for SSI. In Cox proportional hazard models, SSI was independently associated with graft loss (multivariable HR 3.75, 95% CI 1.35-10.38, P = .011). In conclusion, SSI was a rare complication after K-Tx. BMI ≥25 kg/m2 and delayed graft function were independent risk factors. SSIs were independently associated with graft loss.

5.
Diagnostics (Basel) ; 13(13)2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37443593

RESUMEN

The aim of this prospective pilot study was to evaluate the feasibility of a new hybrid imaging modality, free-hand single-photon computed tomography/ultrasonography (fhSPECT/US), for preoperative localization of parathyroid adenomas and to compare its performance with conventional ultrasonography and SPECT/CT. Twelve patients diagnosed with primary hyperparathyroidism underwent sequentially US and parathyroid scintigraphy, including SPECT/CT, followed by fhSPECT/US, allowing for real-time fusion between US and freehand-generated gamma-camera images. The fhSPECT/US detection rates were correlated with histopathology, when available, or with the imaging modality showing the most lesions. Based on a per patient analysis, the detection rate was significantly different when comparing SPECT/CT to fhSPECT/US (p = 0.03), and not significantly different when comparing SPECT/CT to US (p = 0.16) and US to fhSPECT/US (p = 0.08). Based on a per-lesion analysis, the detection rate of SPECT/CT was significantly higher than that of US (p = 0.01) and fhSEPCT/US (p = 0.003), and there was no significant difference in detection rate when comparing US to fhSPECT/US (p = 0.08). The main perceived limitations of fhSPECT/US in lesion detection were: (i) lesions localized at a depth ≥4.5 cm; (ii) imperfect image fusion due to tissue compression; (iii) limited spatial manipulation ability of the SPECT mobile camera handheld probe; and (iv) a wide spread of detected activity. In conclusion, clinical use of fhSPECT/US for localization of parathyroid adenomas is feasible, but shows lower sensitivity than conventional modalities and requires technical improvements.

6.
Eur J Cancer ; 190: 112949, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37453241

RESUMEN

OBJECTIVE: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. MATERIALS AND METHODS: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. RESULTS: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). CONCLUSION: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.


Asunto(s)
Sarcoma de Kaposi , Sarcoma , Neoplasias de los Tejidos Blandos , Adulto , Humanos , Estudios Retrospectivos , Quimioterapia del Cáncer por Perfusión Regional/métodos , Sarcoma/patología , Melfalán/uso terapéutico , Extremidades/patología , Neoplasias de los Tejidos Blandos/patología , Perfusión , Factor de Necrosis Tumoral alfa , Antineoplásicos Alquilantes/uso terapéutico
7.
Rev Med Suisse ; 19(831): 1162-1168, 2023 Jun 14.
Artículo en Francés | MEDLINE | ID: mdl-37314254

RESUMEN

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia due to inappropriate parathyroid hormone (PTH) secretion mostly caused by a single adenoma. Clinical manifestations vary and include bone loss (osteopenia, osteoporosis), kidney stones, asthenia and psychiatric disorders. In 80 % of cases PHPT is asymptomatic. Secondary causes of elevated PTH such as renal insufficiency and/or vitamin D deficiency should be excluded, and 24-hour calciuria should be measured to rule out familial hyocalciuric hypercalcemia. Surgery requires radiological tests: a cervical ultrasound to exclude concomitant thyroid pathology and a functional examination (Sestamibi scintigraphy or F-choline PET scan). Management should be discussed in a multidisciplinary team. Treatment is surgical and can also be offered to asymptomatic patients.


L'hyperparathyroïdie primaire (HPTP) est caractérisée par une hypercalcémie causée par une sécrétion inappropriée de parathormone (PTH) due, dans la majorité des cas, à un adénome parathyroïdien unique. Les manifestations cliniques sont variées, comme la perte osseuse (ostéopénie, ostéoporose), les calculs rénaux, l'asthénie et les troubles psychiatriques. Dans 80 % des cas, l'HPTP est asymptomatique. Il faut exclure une cause secondaire d'élévation de la PTH sur une insuffisance rénale ou un déficit en vitamine D et doser la calciurie sur 24 heures pour exclure une hypercalcémie hypocalciurique familiale. La chirurgie nécessite des examens de radiologie au préalable : un ultrason cervical pour exclure une pathologie thyroïdienne concomitante et un examen fonctionnel (scintigraphie au Sestamibi ou PET-scan à la F-choline). Il est important de discuter de la prise en charge de façon multidisciplinaire. Le traitement curatif est chirurgical et peut aussi être proposé aux patients asymptomatiques.


Asunto(s)
Hipercalcemia , Hiperparatiroidismo Primario , Cálculos Renales , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiología , Hiperparatiroidismo Primario/diagnóstico , Hiperparatiroidismo Primario/cirugía , Astenia , Colina
9.
Semin Nucl Med ; 53(4): 490-502, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36922339

RESUMEN

Primary hyperparathyroidism (1° HPT) is a relatively common endocrine disorder usually caused by autonomous secretion of parathormone by one or several parathyroid adenomas. 1° HPT causing hypercalcemia, kidney stones and/or osteoporosis should be treated whenever possible by parathyroidectomy. Accurate preoperative location of parathyroid adenomas is crucial for surgery planning, mostly when performing minimally invasive surgery. Cervical ultrasonography (US) is usually performed to localize parathyroid adenomas as a first intention, followed by 99mTc- sestamibi scintigraphy with SPECT/CT whenever possible. 4D-CT is a possible alternative to 99mTc- sestamibi scintigraphy. Recently, 18F-fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) has made its way in the clinics as it is the most sensitive method for parathyroid adenoma detection. It can eventually be combined to 4D-CT to increase its diagnostic performance, although this results in higher dose exposure to the patient. Other forms of hyperparathyroidism consist in secondary (2° HPT) and tertiary hyperparathyroidism (3° HPT). As parathyroidectomy is not usually part of the management of patients with 2° HPT, parathyroid imaging is not routinely performed in these patients. In patients with 3° HPT, total or subtotal parathyroidectomy is often performed. Localization of hyperfunctional glands is an important aid to surgery planning. As 18F-FCH PET/CT is the most sensitive modality in multigland disease, it is the preferred imaging technic in 3° HPT patients, although its cost and availability may limit its widespread use in this setting.


Asunto(s)
Hiperparatiroidismo , Neoplasias de las Paratiroides , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de las Paratiroides/complicaciones , Neoplasias de las Paratiroides/diagnóstico por imagen , Neoplasias de las Paratiroides/cirugía , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Hiperparatiroidismo/diagnóstico por imagen , Hiperparatiroidismo/cirugía , Tecnecio Tc 99m Sestamibi , Radiofármacos
10.
Transplant Proc ; 55(2): 337-341, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36813692

RESUMEN

BACKGROUND: Incisional hernias (IH) constitute a complication after kidney transplant (KT). Patients may be particularly at risk because of comorbidities and immunosuppression. The study aim was to assess the incidence, risk factors, and treatment of IH in patients undergoing KT. METHODS: This retrospective cohort study included consecutive patients who underwent KT between January 1998 and December 2018. Patient demographics, comorbidities, perioperative parameters, and IH repair characteristics were assessed. Postoperative outcomes included morbidity, mortality, need for reoperation, and length of stay (LOS). Patients who developed IH were compared with those who did not develop one. RESULTS: Forty-seven patients (6.4%) developed an IH after a median delay of 14 months (IQR, 6-52 months) in 737 KTs. On uni- and multivariate analyses, body mass index (odds ratio [OR], 1.080; P = .020), pulmonary diseases (OR, 2.415; P = .012), postoperative lymphoceles (OR, 2.362; P = .018), and LOS (OR, 1.013; P = .044) were independent risk factors. Thirty-eight patients (81%) underwent operative IH repair, and 37 (97%) were treated with a mesh. The median LOS was 8 days (IQR, 6-11 days). Three patients (8%) developed surgical site infections, and 2 patients (5%) presented hematomas requiring surgical revision. After IH repair, 3 patients (8%) had a recurrence. CONCLUSIONS: The incidence of IH after KT seems rather low. Overweight, pulmonary comorbidities, lymphoceles, and LOS were identified as independent risk factors. Strategies focusing on the modifiable patient-related risk factors and early detection and treatment of lymphoceles may help to decrease the risk of IH formation after KT.


Asunto(s)
Hernia Ventral , Hernia Incisional , Trasplante de Riñón , Linfocele , Humanos , Hernia Incisional/diagnóstico , Hernia Incisional/epidemiología , Hernia Incisional/etiología , Estudios Retrospectivos , Incidencia , Trasplante de Riñón/efectos adversos , Linfocele/epidemiología , Linfocele/etiología , Linfocele/cirugía , Hernia Ventral/cirugía , Factores de Riesgo , Herniorrafia/efectos adversos , Mallas Quirúrgicas/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia
11.
Lancet Oncol ; 24(2): 187-194, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36640790

RESUMEN

BACKGROUND: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy. METHODS: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693. FINDINGS: 282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1-2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0-15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 -21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36-2·17]; p=0·71). INTERPRETATION: This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1-2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort. FUNDING: Swiss Cancer Research foundation.


Asunto(s)
Neoplasias del Apéndice , Tumores Neuroendocrinos , Masculino , Humanos , Femenino , Adulto , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Apendicectomía/efectos adversos , Apendicectomía/métodos , Estudios Retrospectivos , Neoplasias del Apéndice/cirugía , Neoplasias del Apéndice/diagnóstico , Neoplasias del Apéndice/patología , Estudios de Cohortes , Metástasis Linfática , Europa (Continente) , Colectomía/efectos adversos
13.
JAMA Surg ; 157(9): 835-842, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35921122

RESUMEN

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main Outcomes and Measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Melanoma/patología , Pronóstico , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía
14.
Clin Chim Acta ; 534: 146-155, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35905838

RESUMEN

Neuropeptide Y (NPY1-36) is a vasoconstrictor peptide co-secreted with catecholamines by sympathetic nerves, the adrenal medulla, and neoplasms such as pheochromocytomas and paragangliomas (PPGLs). It is produced by the intracellular cleavage of proNPY and metabolized into multiple fragments with distinct biological activities. NPY immunoassays for PPGL have a diagnostic sensitivity ranging from 33 to 100%, depending on the antibody used. We have validated a multiplex micro-UHPLC-MS/MS assay for the specific and sensitive quantification of proNPY, NPY1-39, NPY1-37, NPY1-36, NPY2-36, NPY3-36, NPY1-35, NPY3-35, and the C-flanking peptide of NPY (CPON) (collectively termed NPYs), and determined the NPYs reference intervals and concentrations in 32 PPGL patients before, during, and after surgery. Depending on the peptide measured, NPYs were above the upper reference limit (URL) in 20% to 67% of patients, whereas plasma free metanephrine and normetanephrine, the gold standard for PPGL, were above the URL in 40% and 87% of patients, respectively. Age, sex, tachycardia, and tumor localization were not correlated with NPYs. Plasma free metanephrines performed better than NPYs in the detection of PPGL, but NPYs may be a substitute for an early diagnosis of PPGL for patients that suffer from severe kidney impairment or receiving treatments that interfere with catecholamine reuptake.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Voluntarios Sanos , Humanos , Metanefrina , Neuropéptido Y/metabolismo , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Precursores de Proteínas , Espectrometría de Masas en Tándem
15.
Front Pediatr ; 10: 869518, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35656383

RESUMEN

Background: Neuroblastic neoplasms (NN) include ganglioneuromas (GN), ganglioneuroblastomas (GNB), and neuroblastomas (NB). They generally arise in childhood from primitive sympathetic ganglion cells. Their incidence in adults, especially among elderly, is extremely low. Case Presentation: This is the case of a 74-year-old woman with history of abdominal pain, weakness and night sweating since several months. Blood pressure was normal. CT-scan showed a 10 cm left adrenal mass, without other pathologic findings. An open left-sided adrenalectomy was performed. Recovery was uneventful with hospital length of stay of 8 days. Based on morphological, immunohistochemical, and molecular features the diagnosis was a nodular GNB. A positron emission tomography (PET) performed 6 weeks after the resection did not show any residual tumor or distant metastases. The patient was followed-up with annual clinical and radiological exams. Conclusion: This case presentation, associated with a review of the literature, illustrates the importance to include NN in the preoperative differential diagnosis of adrenal tumors in adults and highlights the need for multidisciplinary patient work-up and management.

16.
Front Endocrinol (Lausanne) ; 13: 794512, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35399933

RESUMEN

Tyrosine kinase inhibitors (TKIs) are nowadays a valuable treatment of desmoid tumors, a rare mesenchymal neoplasm. Although many side effects of imatinib and pazopanib, commonly or rarely occurring, have been described, reactional lymphadenopathy has not yet been reported. In this publication, we report two cases of patients with desmoid tumors, treated with pazopanib and imatinib, who developed reactional lymphadenopathy. As this side effect is presented as a newly formed mass, it can result in new diagnostic questions and added imaging tests and can even lead to discontinuation of the treatment. This report may help the clinicians facing similar problems adopt a "watch and wait" approach.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Fibromatosis Agresiva , Linfadenopatía , Fibromatosis Agresiva/tratamiento farmacológico , Fibromatosis Agresiva/patología , Humanos , Mesilato de Imatinib/efectos adversos , Linfadenopatía/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos
17.
Front Endocrinol (Lausanne) ; 13: 842968, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35282466

RESUMEN

Background: The selectivity index (SI) of cortisol is used to document correct catheter placement during adrenal vein sampling (AVS) in patients with primary aldosteronism (PA). We aimed to determine the cutoff values of the SIs based on cortisol, free metanephrine, and the free-to-total metanephrine ratio (FTMR) using an adapted AVS protocol in combination with CT. Methods: Adults with PA and referred for AVS were recruited in two hypertension centers. The cortisol and free metanephrine-derived SIs were calculated as the concentration of the analyte in adrenal veins divided by the concentration of the analyte in the distal vena cava. The FTMR-derived SI was calculated as the concentration of free metanephrine in the adrenal vein divided by that of total metanephrine in the ipsilateral adrenal vein. The AVS was classified as an unequivocal radiological success (uAVS) if the tip of the catheter was seen in the adrenal vein. The SI cutoffs of each index marker were established using receiver operating characteristic curve analysis. Results: Out of 125 enrolled patients, 65 patients had an uAVS. The SI cutoffs were 2.6 for cortisol, 10.0 for free metanephrine, 0.31 for the FTMR on the left side, and 2.5, 9.9, and 0.25 on the right side. Compared to free metanephrine and the FTMR, cortisol misclassified AVS as unsuccessful in 36.6% and 39.0% of the cases, respectively. Conclusion: This study is the first to calculate the SIs of cortisol, free metanephrine, and the FTMR indices for the AVS procedure. It confirms that free metanephrine-based SIs are better than those based on cortisol.


Asunto(s)
Hiperaldosteronismo , Glándulas Suprarrenales , Adulto , Aldosterona , Catéteres , Humanos , Hidrocortisona , Hiperaldosteronismo/diagnóstico , Metanefrina
18.
J Robot Surg ; 16(6): 1471-1481, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35254601

RESUMEN

Robot-assisted donor nephrectomy (RDN) is increasingly used due to its advantages such as its precision and reduced learning curve when compared to laparoscopic techniques. Concerns remain among surgeons regarding possible longer warm ischemia time. This study aimed to compare patients undergoing robotic living donor nephrectomy to the more frequently used hand-assisted laparoscopic nephrectomy (HLDN) technique, focusing on warm ischemia time, total operative time, learning curve, hospital length of stay, donor renal function and post-operative complications. Retrospective study comparing RDN to HLDN in a collaborative transplant network. 176 patients were included, 72 in RDN and 104 in HLDN. Left-sided nephrectomy was favored in RDN (82% vs 52%, p < 0.01). Operative time was longer in RDN (287 vs 160 min; p < 0.01), while warm ischemia time was similar (221 vs 213 secs, p = 0.446). The hospital stay was shorter in RDN (3.9 vs 5.7 days, p < 0.01).Concerning renal function, a slightpersistent increase of 7% of the creatinine ratio was observed in the RDN compared to the HLDN group (1.56 vs 1.44 at 1-month checkup, p < 0.01). The results show that RDN appears safe and efficient in comparison to the gold-standard HLDN technique. Warm ischemia time was similar for both techniques, whereas RDN operative time was longer. Patients undergoing RDN had a shorter hospital stay, this being possibly mitigated by differences in center release criteria. Donor renal function needs to be assessed on a longer-term basis for both techniques.


Asunto(s)
Laparoscópía Mano-Asistida , Trasplante de Riñón , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Trasplante de Riñón/métodos , Donadores Vivos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos , Creatinina , Nefrectomía/métodos , Laparoscopía/métodos , Riñón/cirugía , Riñón/fisiología
19.
Rev Med Suisse ; 17(743): 1172-1176, 2021 Jun 16.
Artículo en Francés | MEDLINE | ID: mdl-34133095

RESUMEN

Sarcomas are rare tumors divided into two categories: soft tissue sarcomas and bone sarcomas. A soft tissue mass measuring more than 5 cm, deep, growing, atypical or symptomatic should be investigated further and referred to a specialized center. A percutaneous image-guided biopsy should always be performed in suspicious cases. Standard treatment is surgical. Radiotherapy and chemotherapy should be discussed in a multidisciplinary meeting. Recurrence is frequent and close follow-up of patients over the long term is necessary. A high degree of suspicion is required for any atypical abdominal lesion and the patient should be referred to a specialized sarcoma center as soon as possible instead of performing a surgical biopsy.


Les sarcomes sont des tumeurs rares divisées en deux catégories : les sarcomes des tissus mous et les sarcomes ostéoarticulaires. Une masse des tissus mous mesurant plus de 5 cm, profonde, en croissance, atypique ou symptomatique doit faire l'objet d'investigations complémentaires avec demande d'avis d'un centre spécialisé. Une biopsie radioguidée doit toujours être effectuée en cas de suspicion. Le traitement standard est chirurgical. La radiothérapie et la chimiothérapie doivent être discutées dans un colloque multidisciplinaire. La récidive est fréquente et le suivi rapproché et au long cours des patients est nécessaire. Il faut donc avoir un haut degré de suspicion devant toute lésion atypique et référer le patient dès que possible dans un centre spécialisé des sarcomes plutôt que de réaliser une biopsie chirurgicale a minima.


Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Biopsia , Humanos , Recurrencia Local de Neoplasia , Derivación y Consulta , Sarcoma/diagnóstico , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/terapia
20.
Xenotransplantation ; 27(4): e12630, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32698246

RESUMEN

Acute antibody-mediated rejection (AMR) early after transplant remains a challenge, both in allotransplantation and in xenotransplantation. We report the case of an early and severe acute AMR episode in a kidney transplant recipient that was successfully treated with upfront eculizumab. A 58-year-old woman had been on dialysis since 2014. She underwent a first kidney transplant in 2018 with primary non-function and received several blood transfusions. Postoperatively, she developed anti-HLA antibodies. One year later, she received a second allograft from a deceased donor. At day 0, there was only one preformed low-level donor-specific antibody (DSA) anti-DQ7. After initial excellent allograft function, serum creatinine increased on days 7-9, and this was associated with oligo-anuria. On day 7, there was an increase in her DSA anti-DQ7 and 4 de novo DSA had developed at high MFI values. Allograft biopsy showed severe active AMR with diffuse C4d deposits in peritubular capillaries. The early acute AMR episode was treated with upfront eculizumab administration (2 doses) with efficient CH50 blockade (< 10% CH50). Rituximab was also administered on day 12, and intravenous immunoglobulin (IVIG) was given over the following days. There was an excellent clinical response to eculizumab administration. Eculizumab administration rapidly reversed the acute AMR episode without the need for plasmapheresis. Rituximab and IVIG were also used as B-cell immunomodulators to decrease DSA. Blocking efficiently the terminal complement pathway may become a useful strategy to treat acute AMR in sensitized recipients of allografts, and possibly in recipients of discordant xenografts.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Rechazo de Injerto , Isoanticuerpos , Trasplante de Riñón , Femenino , Rechazo de Injerto/prevención & control , Antígenos HLA , Xenoinjertos , Humanos , Riñón/inmunología , Persona de Mediana Edad , Trasplante Heterólogo
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