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2.
J Clin Oncol ; : JCO2101329, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731032

RESUMO

PURPOSE: Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis. Building on this work, we sought to unify and validate an internationally accepted grading scheme for MTC. PATIENTS AND METHODS: Tumor tissue from 327 patients with MTC from five centers across the United States, Europe, and Australia were reviewed for mitotic activity, Ki67 proliferative index, and necrosis using uniform criteria and blinded to other clinicopathologic features. After reviewing different cutoffs, a two-tiered consensus grading system was developed. High-grade MTCs were defined as tumors with at least one of the following features: mitotic index ≥ 5 per 2 mm2, Ki67 proliferative index ≥ 5%, or tumor necrosis. RESULTS: Eighty-one (24.8%) MTCs were high-grade using this scheme. In multivariate analysis, these patients demonstrated decreased overall (hazard ratio [HR] = 11.490; 95% CI, 3.118 to 32.333; P < .001), disease-specific (HR = 8.491; 95% CI, 1.461 to 49.327; P = .017), distant metastasis-free (HR = 2.489; 95% CI, 1.178 to 5.261; P = .017), and locoregional recurrence-free (HR = 2.114; 95% CI, 1.065 to 4.193; P = .032) survivals. This prognostic power was maintained in subgroup analyses of cohorts from each of the five centers. CONCLUSION: This simple two-tiered international grading system is a powerful predictor of adverse outcomes in MTC. As it is based solely on morphologic assessment in conjunction with Ki67 immunohistochemistry, it brings the grading of MTCs in line with other NETs and can be readily applied in routine practice. We therefore recommend grading of MTCs on the basis of mitotic count, Ki67 proliferative index, and tumor necrosis.

3.
JTO Clin Res Rep ; 2(11): 100236, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34766064

RESUMO

Malignant mesothelioma with EWSR1-ATF1 fusion is a rare malignancy described in young adults without asbestos exposure. To the best of our knowledge, outcomes to local and systemic therapies for this subtype of malignant mesothelioma have not been described. This case report describes the clinical course of a 19-year-old man diagnosed with malignant peritoneal mesothelioma with EWSR1-ATF1 fusion localized to the abdomen. His disease followed an aggressive course and resulted in limited survival (18 mo). There was treatment resistance to several lines of conventional local and systemic treatments for peritoneal mesothelioma and biologically targeted MET inhibition with crizotinib. More research is required in this rare subtype of peritoneal mesothelioma.

5.
ANZ J Surg ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34636123

RESUMO

BACKGROUND: The early and accurate diagnosis of pancreatic ductal adenocarcinoma is vital for improving the efficacy of therapeutic interventions and to provide patients with the best chance of survival. While endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been demonstrated to be a reliable and accurate diagnostic tool for solid pancreatic neoplasms, the ongoing management of patients with a high clinical suspicion for malignancy but with a negative EUS-FNA biopsy result can prove a challenge. METHODS: We describe five patients from a single centre who presented for further work-up of a pancreatic mass and/or imaging features concerning for a periampullary malignancy. RESULTS: All patients had at least one EUS-FNA biopsy performed which returned no malignant cells on cytology. Despite these negative cytology results, all patients underwent further invasive investigation through upfront resection (pancreaticoduodenectomy) or extra-pancreatic biopsy (laparoscopic biopsy of peritoneal nodule) due to worrisome features on imaging, biochemical factors and clinical presentation culminating in a high degree of suspicion for malignancy. The final tissue histopathological diagnosis in all patients was pancreatic ductal adenocarcinoma. CONCLUSION: This case series highlights the important clinical findings, imaging and biochemical features which need to be considered in patients who have high suspicion for malignancy despite having a negative EUS-FNA cytology result. In these patients with a high index of suspicion, surgical intervention through an upfront resection or further invasive investigation should not be delayed.

6.
J Hand Surg Am ; 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34702629

RESUMO

PURPOSE: To evaluate the anatomy of nerve transfers used to reconstruct wrist extension, hand opening, and hand closing in tetraplegic patients. METHODS: Nerve transfers were completed on 18 paired cadaveric upper limbs. The overlap of donor and recipient nerves was measured, as well as the distance to the target muscle. Axons were counted in each nerve and branch, with the axon percentage calculated by dividing the donor nerve count by that of the recipient. RESULTS: Transfers with overlap of the donor and recipient nerve were from the radial nerve branch to extensor carpi radialis brevis to anterior interosseous nerve (AIN) and from the branch(es) to supinator to posterior interosseous nerve. The extensor carpi radialis brevis to AIN had the shortest distance to the target, with the branch to brachialis to AIN being the longest. The nerve transfers for wrist extension had the highest axon percentage. Of the transfers for hand closing, the brachialis to AIN had the highest axon percentage, and the branch to brachioradialis to AIN had the lowest. CONCLUSIONS: The anatomical features of nerve transfers used in tetraplegic hand reconstruction are variable. Differences may help explain clinical outcomes. CLINICAL RELEVANCE: This study demonstrates which nerve transfers may be anatomically favorable for restoring hand function in tetraplegic patients.

7.
Front Oncol ; 11: 774861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692555

RESUMO

[This corrects the article DOI: 10.3389/fonc.2021.708963.].

10.
Mod Pathol ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521993

RESUMO

A distinct renal tumor has recently been described as "high-grade oncocytic renal tumor" and "sporadic renal cell carcinoma with eosinophilic and vacuolated cytoplasm". The Genitourinary Pathology Society (GUPS) consensus proposed a unifying name "eosinophilic vacuolated tumor" (EVT) for this emerging entity. In this multi-institutional study, we evaluated 19 EVTs, particularly their molecular features and mutation profile, using next-generation sequencing. All cases were sporadic and none of the patients had a tuberous sclerosis complex. There were 8 men and 11 women, with a mean age of 47 years (median 50; range 15-72 years). Average tumor size was 4.3 cm (median 3.8 cm; range 1.5-11.5 cm). All patients with available follow-up data (18/19) were alive and without evidence of disease recurrence or progression during the follow-up, ranging from 12 to 198 months (mean 56.3, median 41.5 months). The tumors were well circumscribed, but lacked a well-formed capsule, had nested to solid growth, focal tubular architecture, and showed ubiquitous, large intracytoplasmic vacuoles, round to oval nuclei, and prominent nucleoli. Immunohistochemically, cathepsin K, CD117, CD10, and antimitochondrial antigen were expressed in all cases. Other positive stains included: PAX8, AE1/AE3 and CK18. CK7 was typically restricted only to rare scattered cells. Vimentin, HMB45, melan-A, and TFE3 were negative in all cases. All tumors showed retained SDHB. All cases (19/19) showed non-overlapping mutations of the mTOR pathway genes: TSC1 (4), TSC2 (7), and MTOR (8); one case with MTOR mutation showed a coexistent RICTOR missense mutation. Low mutational rates were found in all samples (ranged from 0 to 6 mutations/Mbp). Microsatellite instability and copy number variations were not found in any of the 17 analyzable cases. EVT represents an emerging renal entity that shows a characteristic and readily identifiable morphology, consistent immunohistochemical profile, indolent behavior, and mutations in either TSC1, TSC2, or MTOR genes.

11.
Histopathology ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34523152

RESUMO

AIMS: Amplification of the murine double minute-2 (MDM2) gene, which is usually detected with fluorescence in-situ hybridisation (FISH), is the key driving event for atypical lipomatous tumours (ALTs)/well-differentiated liposarcomas (WDLs). We sought to determine the concordance between the histopathological findings and MDM2 FISH in the diagnosis of ALT/WDL, and to identify the histological features of MDM2-amplified tumours lacking classic atypia. METHODS AND RESULTS: We performed a retrospective analysis of all mature lipomatous lesions subjected to MDM2 FISH analysis at our institution. MDM2 FISH analysis was performed on 439 mature lipomatous lesions: 364 (82.9%) were negative and 75 (17%) were positive. In 17 of 75 (22.6%) ALTs/WDLs, cytological atypia was not identified on initial histological assessment, thus favouring lipoma. On review, these cases shared common histological features, consisting of a very low number of relatively small stromal cells within the tumour lobules, with mildly coarse chromatin and oval nuclei, admixed with unremarkable adipocytes in a tumour background devoid of fibroconnective septa, areas of fibrosis, or blood vessels. These cells matched the cells in which FISH showed MDM2 amplification. In contrast, 13 cases (3.5%) regarded as suspicious for ALT/WDL on the basis of histology lacked MDM2 amplification and were reclassified following the FISH findings. CONCLUSIONS: We conclude that a subset of lipoma-like ALTs/WDLs are not associated with any of the features typically described in ALT/WDL. Our study also showed that tumours >100 mm are more likely to be ALT/WDL; however, a history of recurrence or concerning clinical/radiological features was not significantly associated with classification as ALT/WDL.

14.
Histopathology ; 79(6): 902-912, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34379823

RESUMO

AIMS: Current guidelines for pathology reporting on pancreatic cancer differ in certain aspects, resulting in divergent reporting practices and a lack of comparability of data. Here, we report on a new international dataset for pathology reporting on resection specimens with cancer of the exocrine pancreas (ductal adenocarcinoma and acinar cell carcinoma). The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), which is a global alliance of major (inter)national pathology and cancer organisations. METHODS AND RESULTS: According to the ICCR's rigorous process for dataset development, an international expert panel consisting of pancreatic pathologists, a pancreatic surgeon and an oncologist produced a set of core and non-core data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or non-core element and its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalised and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website. CONCLUSIONS: This first international dataset for cancer of the exocrine pancreas is intended to promote high-quality, standardised pathology reporting. Its widespread adoption will improve the consistency of reporting, facilitate multidisciplinary communication, and enhance the comparability of data, all of which will help to improve the management of pancreatic cancer patients.

15.
ANZ J Surg ; 91(11): 2453-2458, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34427035

RESUMO

BACKGROUNDS: Solid pseudopapillary neoplasms (SPNs) are a distinct but rare form of low-grade pancreatic neoplasia, accounting for 0.3%-2.7% of all pancreatic tumours. They are most common in young females. Local recurrence and distant metastasis are reported but extremely rare, and are usually resectable with curative intent. We report the clinicopathological features and long-term outcomes of SPNs following surgical resection from a single institution. METHODS: A total of 1296 patients undergoing pancreatic resection during the 30 years period from 1991 to 2020 were retrospectively reviewed, and those with a confirmed pathological diagnosis of pancreatic SPN on review were included. RESULTS: Twenty-two patients (1.7% of all patients undergoing resection), were identified. Twenty patients (91%) were female. Unlike previous studies, most patients (91%) were symptomatic at diagnosis. On diagnostic CT, cystic components were visible in 16 patients (73%), calcifications were found in two patients (9%), haemorrhage in one patient (5%) and a defined capsule was seen in four patients (18%). Surgical resection was undertaken on all cases, with distal pancreatectomy the most commonly performed (n = 11, 50%). One patient (4.7%) had nodal involvement, nine patients had an incomplete tumour capsule (41%) and seven patients (32%) had tumour extension into the pancreatic parenchyma. Despite this, no patients had disease recurrence at 10 years. One patient died within 5 years of heart failure unrelated to the SPN process; no patients died within 10 years of the disease. CONCLUSION: We confirm a high proportion of female patients. Interestingly, a high proportion of our cohort was investigated for symptomatic disease. Despite a high proportion of tumours with an incomplete capsule, and extension into the pancreatic parenchyma, our findings indicated that SPN patients have excellent survival after margin-negative surgical resection.


Assuntos
Carcinoma Papilar , Neoplasias Pancreáticas , Carcinoma Papilar/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos
16.
Pathology ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34303553

RESUMO

Several prognostic nomograms designed to predict survival after curative resection for colorectal cancer (CRC) have been proposed. Recently, routine pathological assessment has evolved with subtle changes to the AJCC staging system, and routine screening for mismatch repair deficiency (MMRd). Therefore we sought to develop and validate a new prognostic nomogram. All cause survival data from 4517 consecutive patients with primary CRC were used as independent training and validation cohorts to develop a final model including only: age, sex, tumour stage, nodal status, number of lymph nodes resected, apical node status, distant metastases, thin-walled vascular invasion, and MMR status. Patients were stratified into four risk groups to assess model discrimination and calibration. To assess discrimination, the area-under-the-curve (AUC) of a receiver-operator-curve (ROC), concordance-index (C-index), and D-index were calculated. The model was compared to the Memorial Sloan Kettering Cancer Center (MSKCC) CRC nomogram and the AJCC TNM staging. Based on the 5-year ROC analysis, the AUC for our model was 0.81 (0.79 and 0.74 for MSKCC and AJCC, respectively). Moreover, our model demonstrated a concordance index of 0.77 (95% CI 0.70-0.82) compared to 0.75 (95% CI 0.68-0.81) for MSKCC and 0.73 (95% CI 0.65-0.79) for AJCC. In conclusion, our new prognostic nomogram incorporates a larger number of clinically relevant prognostic markers, including MMR status, and therefore demonstrates improved predictive capability. As these factors are routinely assessed, it is hoped that this model will inform prognostication and difficult management decisions, such as patient selection for adjuvant therapy.

17.
Metabolites ; 11(6)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200432

RESUMO

Pancreatic ß cells secrete the hormone insulin into the bloodstream and are critical in the control of blood glucose concentrations. ß cells are clustered in the micro-organs of the islets of Langerhans, which have a rich capillary network. Recent work has highlighted the intimate spatial connections between ß cells and these capillaries, which lead to the targeting of insulin secretion to the region where the ß cells contact the capillary basement membrane. In addition, ß cells orientate with respect to the capillary contact point and many proteins are differentially distributed at the capillary interface compared with the rest of the cell. Here, we set out to develop an automated image analysis approach to identify individual ß cells within intact islets and to determine if the distribution of insulin across the cells was polarised. Our results show that a U-Net machine learning algorithm correctly identified ß cells and their orientation with respect to the capillaries. Using this information, we then quantified insulin distribution across the ß cells to show enrichment at the capillary interface. We conclude that machine learning is a useful analytical tool to interrogate large image datasets and analyse sub-cellular organisation.

18.
J Clin Med ; 10(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207372

RESUMO

Pancreatic adenocarcinoma is a devastating disease with only 15-20% of patients resectable at diagnosis. Neoadjuvant chemotherapy for this cohort is becoming increasingly popular; however, there are no published randomized trials that support the use of neoadjuvant chemotherapy over upfront surgery in resectable disease. This retrospective cohort analysis was conducted to compare both treatment pathways and to identify any potential prognostic markers. Medical records from one large volume pancreatic cancer center from 2013-2019 were reviewed and 126 patients with upfront resectable disease were analyzed. Due to a change in practice in our center patients treated prior to December 2016 received upfront surgery and those treated after this date received neoadjuvant chemotherapy. Of these, 86 (68%) patients were treated with upfront surgery and 40 (32%) of patients were treated with neoadjuvant chemotherapy. Our results demonstrated that patients treated with upfront surgery with early-stage (1a) disease had a longer median OS compared to those treated with neoadjuvant chemotherapy (24 vs. 21 months, p = 0.028). This survival difference was not evident for all patients (regardless of stage). R0 resections were similar between groups (p = 0.605). We identified that both tumor viability (in neoadjuvant chemotherapy-treated patients) and tumor grade were useful prognostic markers. Upfront surgery for certain patients with low volume disease may be suitable despite the global trend towards neoadjuvant chemotherapy for all upfront resectable patients. A prospective clinical trial in this cohort incorporating biomarkers is needed to determine optimal therapy pathway.

19.
Front Oncol ; 11: 708963, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290990

RESUMO

Background: Patients with pancreatic ductal adenocarcinoma (PDAC) have late diagnosis which results in poor prognosis. Currently, surgical resection is the only option for curative intent. Identifying high-risk features for patients with aggressive PDAC is essential for accurate diagnosis, prognostication, and personalised care due to the disease burden and risk of recurrence despite surgical resection. A panel of three biomarkers identified in tumour tissue (S100A4, Ca125 and Mesothelin) have shown an association with poor prognosis and overall survival. The diagnostic and prognostic value of the serum concentration of this particular biomarker panel for patients with PDAC has not been previously studied. Methods: Retrospectively collected blood samples of PDAC patients (n =120) and healthy controls (n =80) were evaluated for the serum concentration of select biomarkers - S100A4, S100A2, Ca-125, Ca 19-9 and mesothelin. Statistical analyses were performed for diagnostic and prognostic correlation. Results: A panel of four biomarkers (S100A2, S100A4, Ca-125 and Ca 19-9) achieved high diagnostic potential (AUROC 0.913). Three biomarkers (S100A4, Ca-125 and Ca 19-9) correlated with poor overall survival in a univariable model (p < 0.05). PDAC patients with abnormal levels of 2 or more biomarkers in their serum demonstrated significantly lower survival compared to patients with abnormal levels of one or less biomarker (p < 0.05). Conclusion and Impact: The identified biomarker panels have shown the potential to diagnose PDAC patients and stratify patients based on their prognostic outcomes. If independently validated, this may lead to the development of a diagnostic and prognosticating blood test for PDAC.

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