RESUMO
Background A surgical fellowship allows both additional training as well as maintenance of surgical skills while searching for a steady job. As the presence of fellows usually does not results in a measurably higher productivity, fellowshipsmay be considered a form of disguised unemployment. The aim of this study is to evaluate the career flow of a surgical trainee to a staff position and to determine the number of surgeons working on temporary basis within the general surgery workforce in Flanders.Methods All surgeons graduated in Flanders between 2000 and 2022 were invited to fill out a web-based survey concerning their current and past employment. Reminders were sent out after 2 and 4 weeks. Statistical analysis was performed with SPSS version 27.0 (IBM Inc., Chicago, IL, USA.)Results Response rate was 64% (292/457) with 76% of respondents currently working as surgeons, 14% (38) as fellows and 10% working outside the surgical domain. Eighty-two percent of current fellows graduated in 2019 or later. Thirty-one percent of surgeons graduated in 2019 are still working as fellows. For surgeons graduated in 2020, 2021 and 2022 this is 45%, 80% and 90% respectively. Compared to staff surgeons the number of additional training years (2,8 ± 1,0 vs 2,2 ± 1,3; p = 0,009). and the number of applications (6,6 ± 5 vs 3,3 ± 3; p < 0,001) is significantly higher for current fellowsConclusion This study shows that disguised unemployment is present in the general surgical community in Flanders. The status of "fellow" should be incorporated in calculations concerning future needs of the surgical workforce in order to prevent open unemployment.
RESUMO
Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice.
Assuntos
Dor do Câncer , Neoplasias , Humanos , Dor do Câncer/diagnóstico , Dor do Câncer/etiologia , Dor do Câncer/terapia , Medicina de Precisão , Dor , Analgésicos , Neoplasias/complicaçõesRESUMO
BACKGROUND: Breast cancer treatment can lead to sexual dysfunction which, in general, impacts younger women more. Being well informed and having good social support are important elements in dealing with this dysfunction. AIMS: This study aims to explore how specialized breast clinics can help young women with questions or problems regarding their sexual health by fulfilling their information and social support needs. METHOD: A thematic analysis was used for 16 interviews with young women (18-45 years) diagnosed with breast cancer, in Belgium. RESULTS: Participants report a lack of information on sexual issues and find the information insufficiently tailored to young women. The empathy of healthcare providers and their communication skills play an important role in whether sexual issues can be discussed. Finally, they indicate that more attention should be paid to their partner (relationship). CONCLUSION: The breast clinic might help young women by giving more specific advice on what is sexually allowed (or not) during treatment, by informing them about lubricants and sex toys, by adapting brochures and information sessions to young women, by investing in the partner's well-being and their relationship, and by training healthcare providers better.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/terapia , Comportamento Sexual , Sexualidade , Instituições de Assistência Ambulatorial , BélgicaRESUMO
There are multiple imaging modalities in primary hyperparathyroidism. Ultrasound examination and subtraction scintigraphy are usually the first-line imaging techniques. When these results are negative or inconsistent, additional [11C]-methionine PET/CT (MET-PET/CT) or 4-dimensional computed tomography can be performed. âThis study aims to evaluate MET-PET/CT in comparison with other imaging techniques in primary hyperparathyroidism. This is a retrospective cohort study. Eighty-four patients with primary hyperparathyroidism, who underwent parathyroid surgery, were included. âImaging results have been correlated to the perioperative drop in parathyroid hormone level and to the pathological analysis. âDescriptive statistics are used, supplemented with 95% Clopper-Pearson confidence intervals for sensitivity and specificity and a sub-analysis with the McNemar test on paired data only. The per-lesion sensitivity of MET-PET/CT seems higher than that of [99mTc]-sestamibi or [99mTc]-tetrofosmin and [99mTc]-pertechnetate subtraction scintigraphy. The McNemar test, on paired data only, shows significantly higher sensitivity of MET-PET/CT compared to ultrasound (p=0.039) and significantly higher specificity of ultrasound compared to subtraction scintigraphy (p=0.035).â MET-PET/CT after inconclusive or negative ultrasound and/or subtraction scintigraphy has an additional value in 70% of the cases.â Preoperative parathyroid hormone levels were higher in patients in whom MET-PET/CT correctly predicted the pathological parathyroid glands, compared to those where MET-PET/CT missed at least one adenoma. The same trend was seen for 4-dimensional computed tomography. In conclusion, MET-PET/CT seems a valuable imaging modality in primary hyperparathyroidism, at least as second line imaging approach, with a higher per-lesion sensitivity than ultrasound in such setting. Especially when ultrasound and/or subtraction scintigraphy are inconclusive or negative, MET-PET/CT directs the surgeon to the correct localization of the parathyroid adenoma.
Assuntos
Adenoma/diagnóstico , Radioisótopos de Carbono/análise , Metionina/metabolismo , Neoplasias das Paratireoides/diagnóstico , Adenoma/diagnóstico por imagem , Adenoma/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Transplant ureter obstruction is an important cause of graft loss after kidney transplantation. Most cases occur early after transplantation and are related to surgical causes or ischaemic strictures. Underlying mechanisms of late ureteral obstruction are less well understood. CASE REPORT: We present the case of a 61-year-old man who showed gradual decline in renal allograft function and hydronephrosis nine years after transplantation, due to an inguinal herniation of the transplant ureter. After urinary diversion using a percutaneous nephrostomy, graft function restored and the patient underwent surgery. The ureter was reduced from the inguinal hernia and re-implanted in the bladder, with primary closure of the abdominal wall defect. Postoperative course was uneventful and serum creatinine returned to baseline levels. DISCUSSION: Search of relevant literature revealed a number of similar cases, which allowed identification of risk factors associated to the development of uretero-inguinal herniation leading to obstructive nephropathy. Diagnosis of this rare cause of transplant dysfunction and operative treatment strategies are discussed. CONCLUSIONS: Inguinal herniation of the transplant ureter leading to ureteral obstruction is a rare, probably underreported, cause graft of dysfunction. Therefore, we advocate elective repair of inguinal or incisional hernias in renal transplant recipients.
Assuntos
Hérnia Inguinal , Hidronefrose , Transplante de Rim , Ureter , Obstrução Ureteral , Hérnia Inguinal/cirurgia , Humanos , Hidronefrose/etiologia , Hidronefrose/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ureter/cirurgia , Obstrução Ureteral/etiologia , Obstrução Ureteral/cirurgiaRESUMO
PURPOSE: To investigate whether fertility preservation (FP) in adult women diagnosed with breast cancer (BC) may impact the time interval between diagnosis and start of chemotherapy in an adjuvant or neo-adjuvant setting. METHODS: Retrospective cohort study of breast cancer patients diagnosed between January 2012 and December 2017 undergoing FP at a tertiary-care academic fertility centre before neo-adjuvant (NAC) or adjuvant chemotherapy (AC), and matched control breast cancer patients who had no FP. FP interventions included oocyte vitrification following ovarian stimulation or after in-vitro maturation (IVM) of immature oocytes, and/or ovarian tissue cryopreservation. Controls from the patient database of the affiliated Breast Cancer Clinic were matched for tumour characteristics and type of treatment. Time intervals between cancer diagnosis and the start of chemotherapy were analysed. RESULTS: Fifty-nine BC patients underwent FP: 29 received NAC and 30 received AC. The average interval between diagnosis and chemotherapy in BC patients with NAC was 28.5 days (27.3 (range: 14.0-44.0) days in cases and 29.6 (range: 14.0-62.0) days in controls (NS)); this interval was 58.9 days in BC patients with AC (57.2 (range: 36.0-106.0) days in cases and 60.7 (range: 31.0-105.0) days in controls (NS)). CONCLUSION: Fertility preservation does not delay the start of chemotherapy in breast cancer patients.
Assuntos
Neoplasias da Mama , Preservação da Fertilidade , Adulto , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Terapia Neoadjuvante , Indução da Ovulação , Estudos RetrospectivosRESUMO
BACKGROUND: In the majority of familial breast cancer (BC) families, the etiology of the disease remains unresolved. To identify missing BC heritability resulting from relatively rare variants (minor allele frequency ≤ 1%), we have performed whole exome sequencing followed by variant analysis in a virtual panel of 492 cancer-associated genes on BC patients from BRCA1 and BRCA2 negative families with elevated BC risk. METHODS: BC patients from 54 BRCA1 and BRCA2-negative families with elevated BC risk and 120 matched controls were considered for germline DNA whole exome sequencing. Rare variants identified in the exome and in a virtual panel of cancer-associated genes [492 genes associated with different types of (hereditary) cancer] were compared between BC patients and controls. Nonsense, frame-shift indels and splice-site variants (strong protein-damaging variants, called PDAVs later on) observed in BC patients within the genes of the panel, which we estimated to possess the highest probability to predispose to BC, were further validated using an alternative sequencing procedure. RESULTS: Exome- and cancer-associated gene panel-wide variant analysis show that there is no significant difference in the average number of rare variants found in BC patients compared to controls. However, the genes in the cancer-associated gene panel with nonsense variants were more than two-fold over-represented in women with BC and commonly involved in the DNA double-strand break repair process. Approximately 44% (24 of 54) of BC patients harbored 31 PDAVs, of which 11 were novel. These variants were found in genes associated with known or suspected BC predisposition (PALB2, BARD1, CHEK2, RAD51C and FANCA) or in predisposing genes linked to other cancer types but not well-studied in the context of familial BC (EXO1, RECQL4, CCNH, MUS81, TDP1, DCLRE1A, DCLRE1C, PDE11A and RINT1) and genes associated with different hereditary syndromes but not yet clearly associated with familial cancer syndromes (ABCC11, BBS10, CD96, CYP1A1, DHCR7, DNAH11, ESCO2, FLT4, HPS6, MYH8, NME8 and TTC8). Exome-wide, only a few genes appeared to be enriched for PDAVs in the familial BC patients compared to controls. CONCLUSIONS: We have identified a series of novel candidate BC predisposition variants/genes. These variants/genes should be further investigated in larger cohorts/case-control studies. Other studies including co-segregation analyses in affected families, locus-specific loss of heterozygosity and functional studies should shed further light on their relevance for BC risk.
Assuntos
Neoplasias da Mama/genética , Exoma/genética , Predisposição Genética para Doença , Adulto , Idoso , Proteína BRCA1/genética , Proteína BRCA2/genética , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Sequenciamento do ExomaRESUMO
Human epidermal growth factor receptor 2 (HER2) status is used for decision-making in breast carcinoma treatment. The status is obtained through immunohistochemistry or in situ hybridization. These two methods have the disadvantage of necessitating tissue sampling, which is prone to error due to tumor heterogeneity or interobserver variability. Whole-body imaging might be a solution to map HER2 expression throughout the body. Methods: Twenty patients with locally advanced or metastatic breast carcinoma (5 HER2-positive and 15 HER2-negative patients) were included in this phase II trial to assess the repeatability of uptake quantification and the extended safety of the [68Ga]Ga-NOTA-anti-HER2 single-domain antibody (sdAb). The tracer was injected, followed by a PET/CT scan at 90 min. Within 8 d, the procedure was repeated. Blood samples were taken for antidrug antibody (ADA) assessment and liquid biopsies. On available tissues, immunohistochemistry, in situ hybridization, and mass spectrometry were performed to determine the correlation of HER2 status with uptake values measured on PET. If relevant preexisting [18F]FDG PET/CT images were available (performed as standard of care), a comparison was made. Results: With a repeatability coefficient of 21.8%, this imaging technique was repeatable. No clear correlation between PET/CT uptake values and pathology could be established, as even patients with low levels of HER2 expression showed moderate to high uptake. Comparison with [18F]FDG PET/CT in 16 patients demonstrated that in 7 patients, [68Ga]Ga-NOTA-anti-HER2 shows interlesional heterogeneity within the same patient, and [18F]FDG uptake did not show the same heterogeneous uptake in all patients. In some patients, the extent of disease was clearer with the [68Ga]Ga-NOTA-anti-HER2-sdAb. Sixteen adverse events were reported but all without a clear relationship to the tracer. Three patients with preexisting ADAs did not show adverse reactions. No new ADAs developed. Conclusion: [68Ga]Ga-NOTA-anti-HER2-sdAb PET/CT imaging shows similar repeatability to [18F]FDG. It is safe for clinical use. There is tracer uptake in cancer lesions, even in patients previously determined to be HER2-low or -negative. The tracer shows potential in the assessment of interlesional heterogeneity of HER2 expression. In a subset of patients, [68Ga]Ga-NOTA-anti-HER2-sdAb uptake was seen in lesions with no or low [18F]FDG uptake. These findings support further clinical development of [68Ga]Ga-NOTA-anti-HER2-sdAb as a PET/CT tracer in breast cancer patients.
Assuntos
Neoplasias da Mama , Anticorpos de Domínio Único , Humanos , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Anticorpos de Domínio Único/metabolismo , Radioisótopos de Gálio , Fluordesoxiglucose F18 , Neoplasias da Mama/metabolismo , Tomografia por Emissão de PósitronsRESUMO
Radiotherapy treatments for early stage breast cancer patients potentially affect the lung in its most distal air spaces, and previous studies have indicated consistently low baseline values for diffusing capacity in breast cancer patients. We aimed to quantitatively assess baseline small airway function and the acute effects of radiotherapy in breast cancer patients with no confounding effects from respiratory disease or considerable smoking history. In 60 breast cancer patients selected from an ongoing randomized controlled trial, the small airways function was assessed at baseline and 3 months later, after having received either conventional radiotherapy (CR; n = 26) or hypofractionated tomotherapy (TT; n = 34). All indices of small airway function in breast cancer patients were found to be indistinguishable from healthy controls. The total lung capacity was significantly decreased and ventilation heterogeneity was significantly increased 3 months after baseline in the CR arm, but not in the TT arm. When corrected for hemoglobin and lung volume, pulmonary diffusing capacity was not affected by radiotherapy in either treatment arm. Alternatively, discarding patients receiving chemotherapy or loco-regional treatment did not affect these results. We conclude that middle-aged women with breast cancer, but no history of respiratory disease, have normal baseline small airways function. Conventional radiotherapy induces a restrictive pattern and increases heterogeneity of ventilation, the latter most likely resulting from differential expansion between locally irradiated peripheral lung zones and the remainder of the lung. The TT modality did not lead to any such changes.
Assuntos
Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/radioterapia , Pulmão/fisiologia , Adulto , Idoso , Feminino , Humanos , Pulmão/efeitos da radiação , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar , Testes de Função RespiratóriaRESUMO
PURPOSE: To explore the preoperative utility of FDG PET for the diagnosis and prognosis in a retrospective breast cancer case series. METHODS: In this retrospective study, 104 patients who had undergone a preoperative FDG PET scan for primary breast cancer at the UZ Brussel during the period 2002-2008 were identified. Selection criteria were: histological confirmation, FDG PET performed prior to therapy, and breast surgery integrated into the primary therapy plan. Patterns of increased metabolism were recorded according to the involved locations: breast, ipsilateral axillary region, internal mammary chain, or distant organs. The end-point for the survival analysis using Cox proportional hazards was disease-free survival. The contribution of prognostic factors was evaluated using the Akaike information criterion and the Nagelkerke index. RESULTS: PET positivity was associated with age, gender, tumour location, tumour size >2 cm, lymphovascular invasion, oestrogen and progesterone receptor status. Among 63 patients with a negative axillary PET status, 56 (88.9 %) had three or fewer involved nodes, whereas among 41 patients with a positive axillary PET status, 25 (61.0 %) had more than three positive nodes (P < 0.0001). In the survival analysis of preoperative characteristics, PET axillary node positivity was the foremost statistically significant factor associated with decreased disease-free survival (hazard ratio 2.81, 95% CI 1.17-6.74). CONCLUSION: Preoperative PET axillary node positivity identified patients with a higher burden of nodal involvement, which might be important for treatment decisions in breast cancer patients.
Assuntos
Neoplasias da Mama Masculina/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Adulto , Neoplasias da Mama Masculina/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Scapula alata (SA) is a known complication of breast surgery associated with palsy of the serratus anterior, but it is seldom mentioned. We evaluated the risk factors associated with SA and the relationship of SA with ipsilateral shoulder/arm morbidity in a series of patients enrolled in a trial of post-surgery radiotherapy (RT). METHODS: The trial randomized women with completely resected stage I-II breast cancer to short-course image-guided RT, versus conventional RT. SA, arm volume and shoulder-arm mobility were measured prior to RT and at one to three months post-RT. Shoulder/arm morbidities were computed as a post-RT percentage change relative to pre-RT measurements. RESULTS: Of 119 evaluable patients, 13 (= 10.9%) had pre-RT SA. Age younger than 50 years old, a body mass index less than 25 kg/m2, and axillary lymph node dissection were significant risk factors, with odds ratios of 4.8 (P = 0.009), 6.1 (P = 0.016), and 6.1 (P = 0.005), respectively. Randomization group was not significant. At one to three months' post-RT, mean arm volume increased by 4.1% (P = 0.036) and abduction decreased by 8.6% (P = 0.046) among SA patients, but not among non-SA patients. SA resolved in eight, persisted in five, and appeared in one patient. CONCLUSION: The relationship of SA with lower body mass index suggests that SA might have been underestimated in overweight patients. Despite apparent resolution of SA in most patients, pre-RT SA portended an increased risk of shoulder/arm morbidity. We argue that SA warrants further investigation. Incidentally, the observation of SA occurring after RT in one patient represents the second case of post-RT SA reported in the literature.
Assuntos
Neoplasias da Mama/radioterapia , Mastectomia , Paralisia/etiologia , Complicações Pós-Operatórias/etiologia , Radioterapia Guiada por Imagem , Escápula/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Pessoa de Meia-Idade , Paralisia/epidemiologia , Paralisia/patologia , Paralisia/fisiopatologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Radioterapia Adjuvante , Amplitude de Movimento Articular , Fatores de Risco , Articulação do Ombro/fisiopatologia , Método Simples-CegoRESUMO
INTRODUCTION: Centrally located breast tumors represent a challenge for both oncological and reconstructive surgeons, mainly due to the necessity of nipple-areola complex (NAC) removal. We describe an original oncoplastic solution utilizing a displacement flap technique with immediate nipple reconstruction. METHODS: Since 2008, we developed an oncoplastic technique using a septum-based island flap for the reconstruction of central breast defects, including the NAC. This technique is based on the Würinger's septum which is centered around the intercostal perforators. A retrospective study was performed collecting data on patient characteristics, oncological features, and outcomes. Patient satisfaction was reported using a Likert scale. RESULTS: Reconstruction was successfully realized in 15 patients (14 immediate and one delayed post-lumpectomy correction). In immediate surgery, the excision margins were all free of tumor. Minor complications occurred in three patients; one small area of skin necrosis was managed by secondary intention, and two cases of partial nipple necrosis were treated by debridement under local anesthesia. Contralateral symmetrization surgery was performed on nine patients. Patient satisfaction scored high. CONCLUSION: In comparison with the previous oncoplastic techniques used for reconstructing central defects, the septum-based island flap has increased flexibility, provides better projection, and can be combined with immediate NAC reconstruction.
Assuntos
Neoplasias da Mama , Mamoplastia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/métodos , Necrose , Mamilos/cirurgia , Estudos Retrospectivos , Retalhos Cirúrgicos/cirurgiaRESUMO
Patients fulfilling criteria for euthanasia can choose to donate their organs after circulatory death [donors after euthanasia (DCD V)]. This study assesses the outcome of islet cell isolation from DCD V pancreases. A procedure for DCD V procurement provided 13 pancreases preserved in Institut Georges Lopez-1 preservation solution and following acirculatory warm ischemia time under 10 minutes. Islet cell isolation outcomes are compared with those from reference donors after brain death (DBD, n = 234) and a cohort of donors after controlled circulatory death (DCD III, n = 29) procured under the same conditions. Islet cell isolation from DCD V organs resulted in better in vitro outcome than for selected DCD III or reference DBD organs. A 50% higher average beta cell number before and after culture and a higher average beta cell purity (35% vs 24% and 25%) was observed, which led to more frequent selection for our clinical protocol (77% of isolates vs 50%). The functional capacity of a DCD V islet cell preparation was illustrated by its in vivo effect following intraportal transplantation in a type 1 diabetes patient: injection of 2 million beta cells/kg body weight (1,900 IEQ/kg body weight) at 39% insulin purity resulted in an implant with functional beta cell mass that represented 30% of that in non-diabetic controls. In conclusion, this study describes procurement and preservation conditions for donor organs after euthanasia, which allow preparation of cultured islet cells, that more frequently meet criteria for clinical use than those from DBD or DCD III organs.
Assuntos
Células Secretoras de Insulina , Doadores de Tecidos , Peso Corporal , Morte Encefálica , Eutanásia , Humanos , Células Secretoras de Insulina/transplante , PâncreasRESUMO
Scoring of tumor-infiltrating lymphocytes (TILs) in breast cancer specimens has gained increasing attention, as TILs have prognostic and predictive value in HER2+ and triple-negative breast cancer. We evaluated the intra- and interrater variability when scoring TILs by visual inspection of hematoxylin and eosin-stained tissue sections. We further addressed whether immunohistochemical staining of these sections for immune cell surface markers CD45, CD3, CD4, and CD8 and combination with nanoString nCounter® gene expression analysis could refine TIL scoring. Formalin-fixed paraffin-embedded and fresh-frozen core needle biopsies of 12 female and treatment-naive breast cancer patients were included. Scoring of TILs was performed twice by three independent pathologists with a washout period of 3 days. Increasing intra- and interrater variability was observed with higher TIL numbers. The highest reproducibility was observed on tissue sections stained for CD3 and CD8. The latter TIL scores correlated well with the TIL scores obtained through nanoString nCounter® gene expression analysis. Gene expression analysis also revealed 104 and 62 genes that are positively and negatively related to both TIL scores. In conclusion, integration of immunohistochemistry and gene expression analysis is a valuable strategy to refine TIL scoring in breast tumors.
Assuntos
Linfócitos do Interstício Tumoral , Neoplasias de Mama Triplo Negativas , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Reprodutibilidade dos TestesRESUMO
Organs from donors after controlled circulatory death (DCD III) exhibit a higher risk for graft dysfunction due to an initial period of warm ischemia. This procurement condition can also affect the yield of beta cells in islet isolates from donor pancreases, and hence their use for transplantation. The present study uses data collected and generated by our Beta Cell Bank to compare the number of beta cells in isolates from DCD III (n = 141) with that from donors after brain death (DBD, n = 609), before and after culture, and examines the influence of donor and procurement variables. Beta cell number per DCD III-organ was significantly lower (58 x 106 versus 84 x 106 beta cells per DBD-organ; p < 0.001) but their purity (24% insulin positive cells) and insulin content (17 µg / 106 beta cells in DCD III-organs versus 19 µg / 106 beta cells in DBD-organs) were similar. Beta cell number correlated negatively with duration of acirculatory warm ischemia time above 10 min; for shorter acirculatory warm ischemia time, DCD III-organs did not exhibit a lower beta cell yield (74 x 106 beta cells). Use of Institut Georges Lopez-1 cold preservation solution instead of University of Wisconsin solution or histidine-tryptophan-ketoglutarate also protected against the loss in beta cell yield from DCD III-organs (86 x 106 for IGL-1 versus 54 x 106 and 65 x 106 beta cells respectively, p = 0.042). Multivariate analysis indicates that both limitation of acirculatory warm ischemia time and use of IGL-1 prevent the reduced beta cell yield in islet cell isolates from DCD III-organs.
Assuntos
Morte Encefálica/metabolismo , Morte Encefálica/patologia , Sobrevivência de Enxerto/fisiologia , Células Secretoras de Insulina/fisiologia , Soluções para Preservação de Órgãos/metabolismo , Adenosina/metabolismo , Adenosina/fisiologia , Adulto , Alopurinol/metabolismo , Feminino , Glutaratos/metabolismo , Glutationa/metabolismo , Glutationa/fisiologia , Histidina/metabolismo , Humanos , Insulina/metabolismo , Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Rafinose/metabolismo , Rafinose/fisiologia , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Triptofano/metabolismo , Isquemia Quente/métodosRESUMO
The use of gene expression profiling (GEP) in cancer management is rising, as GEP can be used for disease classification and diagnosis, tailoring treatment to underlying genetic determinants of pharmacological response, monitoring of therapy response, and prognosis. However, the reliability of GEP heavily depends on the input of RNA in sufficient quantity and quality. This highlights the need for standard procedures to ensure best practices for RNA extraction from often small tumor biopsies with variable tissue handling. We optimized an RNA extraction protocol from fresh-frozen (FF) core needle biopsies (CNB) from breast cancer patients and from formalin-fixed paraffin-embedded (FFPE) tissue when FF CNB did not yield sufficient RNA. Methods to avoid ribonucleases andto homogenize or to deparaffinize tissues and the impact of tissue composition on RNA extraction were studied. Additionally, RNA's compatibility with the nanoString nCounter® technology was studied. This technology platform enables GEP using small RNA fragments. After optimization of the protocol, RNA of high quality and sufficient quantity was obtained from FF CNB in 92% of samples. For the remaining 8% of cases, FFPE material prepared by the pathology department was used for RNA extraction. Both resulting RNA end products are compatible with the nanoString nCounter® technology.
Assuntos
Biópsia com Agulha de Grande Calibre/métodos , RNA/isolamento & purificação , Manejo de Espécimes/métodos , Biópsia com Agulha de Grande Calibre/normas , Neoplasias da Mama/genética , Perfilação da Expressão Gênica/métodos , Humanos , Análise em Microsséries/métodos , RNA/genética , RNA/normas , Reprodutibilidade dos Testes , Manejo de Espécimes/normasRESUMO
PURPOSE: To evaluate the overall survival prognostic value of preoperative 18F-fluorodeoxyglucose positron emission tomography (PET) in breast cancer, as compared with the lymph node ratio (LNR). METHODS: Data were abstracted at a median follow-up 14.7 years from a retrospective cohort of 104 patients who underwent PET imaging before curative surgery. PET-Axillary|Sternal was classified as PET-positive if hypermetabolism was visualized in ipsilateral nodal axillary and/or sternal region, else as PET-negative. The differences of 15 years restricted mean survival time ∆RMST according to PET and LNR were computed from Kaplan-Meier overall survival. The effect of PET and other patients' characteristics was analyzed through rankit normalization, which provides with Cox regression the Royston-Sauerbrei D measure of separation to compare the characteristics (0 indicating no prognostic value). Multivariate analysis of the normalized characteristics used stepwise selection with the Akaike information criterion. RESULTS: In Kaplan-Meier analysis, LNR > 0.20 versus ≤ 0.20 showed ∆RMST = 3.4 years, P = 0.003. PET-Axillary|Sternal positivity versus PET-negative showed a ∆RMST = 2.6 years, P = 0.008. In Cox univariate analyses, LNR appeared as topmost prognostic separator, D = 1.50, P < 0.001. PET ranked below but was also highly significant, D = 1.02, P = 0.009. In multivariate analyses, LNR and PET-Axillary|Sternal were colinear and mutually exclusive. PET-Axillary|Sternal improved as prognosticator in a model excluding lymph nodes, yielding a normalized hazard ratio of 2.44, P = 0.062. CONCLUSION: Pathological lymph node assessment remains the gold standard of prognosis. However, PET appears as a valuable surrogate in univariate analysis at 15-year follow-up. There was a trend towards significance in multivariate analysis that warrants further investigation.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Cuidados Pré-Operatórios/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Estudos RetrospectivosRESUMO
131I-GMIB-anti-human epidermal growth factor receptor type 2 (HER2)-VHH1 is a targeted radionuclide theranostic agent directed at HER2-expressing cancers. VHH1 is a single-domain antibody covalently linked to therapeutic 131I via the linker N-succinimidyl 4-guanidino-methyl-3-iodobenzoate (SGMIB). The phase I study was aimed at evaluating the safety, biodistribution, radiation dosimetry, and tumor-imaging potential of 131I-GMIB-anti-HER2-VHH1 in healthy volunteers and breast cancer patients. Methods: In a first cohort, 6 healthy volunteers were included. The biodistribution of 131I-GMIB-anti-HER2-VHH1 was assessed using whole-body (anterior and posterior) planar images obtained at 40 min and at 2, 4, 24, and 72 h after intravenously administered (38 ± 9 MBq) 131I-GMIB-anti-HER2-VHH1. Imaging data were analyzed using OLINDA/EXM software to determine the dosimetry. Blood and urine samples were obtained over 72 h. In the second cohort, 3 patients with metastatic HER2-positive breast cancer were included. Planar whole-body imaging was performed at 2 and 24 h after injection. Additional SPECT/CT images were obtained after the whole-body images at 2 and 24 h if there was relevant uptake in known cancer lesions. Results: No drug-related adverse events were observed throughout the study. The biologic half-life of 131I-GMIB-anti-HER2-VHH1 in healthy subjects was about 8 h. After intravenous administration, the compound was eliminated from the blood with a 2.5-h half-life. The drug was eliminated primarily via the kidneys. The drug was stable in circulation, and there was no increased accumulation in the thyroid or stomach. The absorbed dose to the kidneys was 1.54 ± 0.25 mGy/MBq, and to bone marrow it was 0.03 ± 0.01 mGy/MBq. SPECT/CT imaging in patients with advanced breast cancer showed focal uptake of 131I-GMIB-anti-HER2-VHH1 in metastatic lesions. Conclusion: Because of its favorable toxicity profile and its uptake in HER2-positive lesions, this radiopharmaceutical can offer new therapeutic options to patients who have progressed on trastuzumab, pertuzumab, or trastuzmab emtansine, given its difference in mode-of-action. A dose escalation is planned in a subsequent phase I/II study to assess the therapeutic window of this compound (NCT04467515).
Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Distribuição Tecidual , TrastuzumabRESUMO
We report a case of a male infant who underwent resection of a unilateral breast mass with a histopathological diagnosis of a fibrous hamartoma of infancy (FHI) combined with a pseudoangiomatous stromal hyperplasia (PASH). Breast lumps are uncommon in infants and children, especially in boys. FHI and PASH are very rare causes of breast lumps, especially in infants. To our knowledge, this is the first report of a combination of both pathologies in 1 lesion in the breast of an infant.