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1.
Surg Endosc ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874609

RESUMO

BACKGROUND: Liver surgery is associated with a significant hospital stay regardless the type of liver resection. A large incision is essential for open liver surgery which is a major factor in the course of the patient's recovery. For patients with small parenchyma liver lesions requiring surgical resection, robotic surgery potentially offers the opportunity to transform the patient's post-operative course. A day-case robotic liver resection pathway was formulated and implemented at our institution when patients were planned for discharge within 24 h of admission for liver surgery. METHODS: Single surgeon case series of cases performed at a tertiary hepatobiliary and pancreatic centre between September 2022 and November 2023. The inclusion criteria were non-anatomical wedge resections, < 2 anatomical segmental resections, left lateral hepatectomy and minimally invasive surgery. RESULTS: This is the first series of robotic day-case minor liver resection in the United Kingdom. 20 patients were included in this case series. The mean operative time was 86.6 ± 30.9 min and mean console time was 58.6 ± 24.5 min. Thirteen patients (65%) were discharged within 24 h of surgery. The main cause of hospitalisation beyond 24 h was inadequate pain relief. There were no Clavien-Dindo grade III or above complications, no 30-day readmission and 90-day mortalities. CONCLUSION: This case series demonstrates that robotic day-case liver resection is safe and feasible. Robust follow-up pathways must be in place to allow for the safe implementation of this approach, to monitor for any complications and to allow intervention as required in a timely manner.

2.
Cancers (Basel) ; 15(22)2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38001752

RESUMO

Technical limitations of laparoscopic distal pancreatectomy (LDP), in comparison to robotic distal pancreatectomy (RDP), may translate to high conversion rates and morbidity. LDP and RDP procedures performed between December 2008 and January 2023 in our tertiary referral hepatobiliary and pancreatic centres were analysed and compared with regard to short-term outcomes. A total of 62 consecutive LDP cases and 61 RDP cases were performed. There was more conversion to open surgeries in the laparoscopic group compared with the robotic group (21.0% vs. 1.6%, p = 0.001). The LDP group also had a higher rate of postoperative complications (43.5% vs. 23.0%, p = 0.005). However, there was no significant difference between the two groups in terms of major complication or pancreatic fistular after operations (p = 0.20 and p = 0.71, respectively). For planned spleen-preserving operations, the RDP group had a shorter mean operative time (147 min vs. 194 min, p = 0.015) and a reduced total length of hospital stay compared with the LDP group (4 days vs. 7 days, p = 0.0002). The failure rate for spleen preservation was 0% in RDP and 20% (n = 5/25) in the LDP group (p = 0.009). RDP offered a better method for splenic preservation with Kimura's technique compared with LDP to avoid the risk of splenic infarction and gastric varices related to ligation and division of splenic pedicles. RDP should be the standard operation for the resection of pancreatic tumours at the body and tail of the pancreas without involving the celiac axis or common hepatic artery.

3.
BMJ Open ; 13(10): e076621, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37802612

RESUMO

INTRODUCTION: Patients undergoing prostate radiotherapy with an enlarged prostate can have short-term and long-term urinary complications. Currently, transurethral resection of the prostate (TURP) is the mainstay surgical intervention for men with urinary symptoms due to an enlarged prostate prior to radiotherapy. UroLift (NeoTract, Pleasanton, CA, USA) is a recent minimally invasive alternative, widely used in benign disease but is untested in men with prostate cancer. METHODS AND ANALYSIS: A multicentre, two-arm study designed in collaboration with a Patient Reference Group to assess the feasibility of randomising men with prostate cancer and coexisting urinary symptoms due to prostate enlargement to TURP or UroLift ahead of radiotherapy. 45 patients will be enrolled and randomised (1:1) using a computer-generated programme to TURP or UroLift. Recruitment and retention will be assessed over a 12 month period. Information on clinical outcomes, adverse events and costs will be collected. Clinical outcomes and patient reported outcome measures will be measured at baseline, 6 weeks postintervention and 3 months following radiotherapy. A further 12 in-depth interviews will be conducted with a subset of patients to assess acceptability using the Theoretical Framework of Acceptability. Descriptive analysis on all outcomes will be performed using Stata (StataCorp V.2021). ETHICS AND DISSEMINATION: The trial has been approved by the Research Ethics Committee (REC) NHS Health Research Authority (HRA) and Health and Care Research Wales (HCRW). The results will be published in peer-reviewed journals, presented at national meetings and disseminated to patients via social media, charity and hospital websites. TRIAL REGISTRATION NUMBER: NCT05840549.


Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Ressecção Transuretral da Próstata , Humanos , Masculino , Estudos de Viabilidade , Londres , Próstata , Hiperplasia Prostática/complicações , Hiperplasia Prostática/radioterapia , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/complicações , Ressecção Transuretral da Próstata/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
J Clin Oncol ; 41(34): 5296-5305, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656935

RESUMO

PURPOSE: No consensus exists on the management of men with nonseminoma and viable nonteratomatous germ cell tumor in the postchemotherapy retroperitoneal lymph node dissection (pcRPLND) specimen after first-line chemotherapy. We analyzed surveillance versus different adjuvant chemotherapy regimens and the influence of time to pcRPLND on oncologic outcomes. METHODS: Data on 117 men treated with cisplatin-based first-line chemotherapy between 1990 and 2018 were collected from 13 institutions. All patients had viable nonteratomatous germ cell tumor in the pcRPLND specimen. Surgery was performed after a median of 57 days, followed by either surveillance (n = 64) or adjuvant chemotherapy (n = 53). Primary end points were progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: After controlling for International Germ Cell Cancer Cooperative Group risk group and percent of viable malignant cells found at RPLND, no difference was observed between men managed with surveillance or adjuvant chemotherapy regarding PFS (hazard ratio [HR], 0.72 [95% CI, 0.32 to 1.6]; P = .4), CSS (HR, 0.69; 95% CI, 0.20 to 2.39; P = .6), and OS (HR, 0.78 [95% CI, 0.25 to 2.44]; P = .7). No statistically significant differences for PFS, CSS, or OS were observed on the basis of chemotherapy regimen or in men treated with pcRPLND ≤57 versus >57 days after first-line chemotherapy. Residual disease with <10% versus ≥10% viable cancer cells were associated with a longer PFS (HR, 3.22 [95% CI, 1.29 to 8]; P = .012). Relapse in the retroperitoneum was observed in 34 (29%) men. CONCLUSION: Men with a complete resection at pcRPLND and <10% viable cells have favorable outcomes without further treatment. Complete retroperitoneal resection seems more important than early pcRPLND.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , Feminino , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Neoplasia Residual , Estudos Retrospectivos , Excisão de Linfonodo , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Espaço Retroperitoneal/patologia , Fatores de Risco , Recidiva , Resultado do Tratamento
5.
BJU Int ; 132(5): 541-553, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37436368

RESUMO

OBJECTIVES: To report the NHS Digital (NHSD) data for patients diagnosed with kidney cancer (KC) in England. We explore the incidence, route to diagnosis (RTD), treatment, and survival patterns from 2013 to 2019. MATERIALS AND METHODS: Data was extracted from the Cancer Data NHSD portal for International Classification of Diseases, 10th edition coded KC; this included Cancer Registry data, Hospital Episode Statistics, and cancer waiting times data. RESULTS: Registrations included 66 696 individuals with KC. Incidence of new KC diagnoses increased (8998 in 2013, to 10 232 in 2019), but the age-standardised rates were stable (18.7-19.4/100 000 population). Almost half of patients (30 340 [45.5%]) were aged 0-70 years and the cohort were most frequently diagnosed with Stage 1-2 KC (n = 26 297 [39.4%]). Most patients were diagnosed through non-urgent general practitioner referrals (n = 16 814 [30.4%]), followed by 2-week-wait (n = 15 472 [28.0%]) and emergency routes (n = 11 796 [21.3%]), with older patients (aged ≥70 years), Stage 4 KCs, and patients with non-specified renal cell carcinoma being significantly more likely to present through the emergency route (all P < 0.001). Invasive treatment (surgery or ablation), radiotherapy, or systemic anti-cancer therapy use varied with disease stage, patient factors, and treatment network (Cancer Alliance). Survival outcomes differed by Stage, histological subtype, and social deprivation class (P < 0.001). Age-standardised mortality rates did not change over the study duration, although immunotherapy usage is likely not captured in this study timeline. CONCLUSION: The NHSD resource provides useful insight about the incidence, diagnostic pathways, treatment, and survival of patients with KC in England and a useful benchmark for the upcoming commissioned National Kidney Cancer Audit. The RTD data may be limited by incidental diagnoses, which could confound the high proportion of 'emergency' diagnoses. Importantly, survival outcomes remained relatively unchanged.

6.
Prostate Cancer Prostatic Dis ; 26(3): 614-624, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37264224

RESUMO

BACKGROUND: Prostate cancer is a broad-spectrum disease, spanning from indolent to a highly aggressive lethal malignancy. Prostate cancer cell lines are essential tools to understanding the basic features of this malignancy, as well as in identifying novel therapeutic strategies. However, most cell lines routinely used in prostate cancer research are derived from metastatic disease and may not fully elucidate the molecular events underlying the early stages of cancer development and progression. Thus, there is a need for new cell lines derived from localised disease to better span the disease spectrum. METHODS: Prostatic tissue from the primary site, and adjacent non-cancerous tissue was obtained from four patients with localised disease undergoing radical prostatectomy. Epithelial cell outgrowths were immortalised with human papillomavirus type 16 (HPV16) E6 and E7 to establish monoclonal cell lines. Chromosomal ploidy was imaged and STR profiles were determined. Cell morphology, colony formation and cell proliferation characteristics were assessed. Androgen receptor (AR) expression and AR-responsiveness to androgen treatment were analysed by immunofluorescence and RT-qPCR, respectively. RNA-seq analysis was performed to identify prostate lineage markers and expression of prostate cancer tumorigenesis-related genes. RESULTS: Two benign cell lines derived from non-cancer cells (AQ0420 and AQ0396) and two tumour tissue derived cancer cell lines (AQ0411 and AQ0415) were immortalised from four patients with localised prostatic adenocarcinoma. The cell lines presented an epithelial morphology and a slow to moderate proliferative rate. None of the cell lines formed anchorage independent colonies or displayed AR-responsiveness. Comparative RNA-seq expression analysis confirmed the prostatic lineage of the four cell lines, with a distinct gene expression profile from that of the metastatic prostate cancer cell lines, PC-3 and LNCaP. CONCLUSIONS: Comprehensive characterization of these cell lines may provide new in vitro tools that could bridge the current knowledge gap between benign, early-stage and metastatic disease.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Próstata/patologia , Linhagem Celular , Antígeno Prostático Específico/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/análise , Androgênios/metabolismo , Linhagem Celular Tumoral
7.
Eur Urol ; 84(3): 289-301, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37183161

RESUMO

CONTEXT: Each year the European Association of Urology (EAU) produce a document based on the most recent evidence on the diagnosis, therapy, and follow-up of testicular cancer (TC). OBJECTIVE: To represent a summarised version of the EAU guidelines on TC for 2023 with a focus on key changes in the 2023 update. EVIDENCE ACQUISITION: A multidisciplinary panel of TC experts, comprising urologists, medical and radiation oncologists, and pathologists, reviewed the results from a structured literature search to compile the guidelines document. Each recommendation in the guidelines was assigned a strength rating. EVIDENCE SYNTHESIS: For the 2023 EAU guidelines on TC, a review and restructure were undertaken. The key changes incorporated in the 2023 update include: new supporting text regarding venous thromboembolism prophylaxis in males with metastatic germ cell tumours receiving chemotherapy; quality of life after treatment; an update of the histological classifications and inclusion of the World Health Organization 2022 pathological classification; inclusion of the revalidation of the 1997 International Germ Cell Cancer Collaborative Group prognostic risk factors; and a new section covering oncology treatment protocols. CONCLUSIONS: The 2023 version of the EAU guidelines on TC include the highest available scientific evidence to standardise the management of TC. Better stratification and optimisation of treatment modalities will continue to improve the high survival rates for patients with TC. PATIENT SUMMARY: This article presents a summary of the European Association of Urology guidelines on testicular cancer published in 2023 and includes the latest recommendations for management of this disease. The guidelines are a valuable resource that may help patients in understanding treatment recommendations.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Urologia , Masculino , Humanos , Neoplasias Testiculares/terapia , Neoplasias Testiculares/diagnóstico , Qualidade de Vida , Neoplasias Embrionárias de Células Germinativas/terapia
8.
Nat Rev Urol ; 20(8): 502-512, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36882564

RESUMO

International Germ Cell Cancer Collaborative Group good-risk metastatic seminoma has cure rates of >95%. Within this risk group, patients with stage II disease exhibit the best oncological outcomes with the standard-of-care treatment strategies of radiotherapy or combination chemotherapy. However, these treatments can be associated with substantial early and late toxic effects. Therapy de-escalation aims to reduce treatment morbidity whilst preserving oncological outcomes. The evidence supporting such approaches is largely from non-randomized institutional data, and therefore this strategy is not recognized as standard of care. Current de-escalation approaches for stage II seminoma include single-agent chemotherapy, radiotherapy and surgery based on early data from clinical studies. Increased recognition of emerging data on treatment modification to reduce morbidity whilst maintaining cure rates and consideration of therapy de-escalation could improve patient survivorship outcomes.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Seminoma/terapia , Neoplasias Testiculares/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Quimioterapia Adjuvante , Fatores de Risco , Estadiamento de Neoplasias
9.
Surg Endosc ; 37(6): 4719-4727, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36890417

RESUMO

BACKGROUND: An increasing number of robotic pancreatoduodenectomies (RPD) are reported, however, questions remain on the number of procedures needed for gaining technical proficiency in RPD. Therefore, we aimed to assess the influence of procedure volume on short-term RPD outcomes and assess the learning curve effect. METHODS: A retrospective review of consecutive RPD cases was undertaken. Non-adjusted cumulative sum (CUSUM) analysis was performed to identify the procedure volume threshold, following which before-threshold and after-threshold outcomes were compared. RESULTS: Since May 2017, 60 patients had undergone an RPD at our institution. The median operative time was 360 min (IQR 302.25-442 min). CUSUM analysis of operative time identified 21 cases as proficiency threshold, indicated by curve inflexion. Median operative time was significantly shorter after the threshold of 21 cases (470 vs 320 min, p < 0.001). No significant difference was found between before- and after-threshold groups in major Clavien-Dindo complications (23.8 vs 25.6%, p = 0.876). CONCLUSIONS: A decrease in operative time after 21 RPD cases suggests a threshold of technical proficiency potentially associated with an initial adjustment to new instrumentation, port placement and standardisation of operative step sequence. RPD can be safely performed by surgeons with prior laparoscopic surgery experience.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Estudos de Coortes , Pancreaticoduodenectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Curva de Aprendizado , Estudos Retrospectivos , Duração da Cirurgia , Laparoscopia/métodos
11.
Cancers (Basel) ; 15(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36672404

RESUMO

The benefits and prognosis of RPLND in CRC have not yet been fully established. This systematic review aimed to evaluate the outcomes for CRC patients with RPLNM undergoing RPLND. A literature search of MEDLINE, EMBASE, EMCare, and CINAHL identified studies from between January 1990 and June 2022 that reported data on clinical outcomes for patients who underwent RPLND for RPLNM in CRC. The following primary outcome measures were derived: postoperative morbidity, disease free-survival (DFS), overall survival (OS), and re-recurrence. Nineteen studies with a total of 541 patients were included. Three hundred and sixty-three patients (67.1%) had synchronous RPLNM and 178 patients (32.9%) had metachronous RPLNM. Perioperative chemotherapy was administered in 496 (91.7%) patients. The median DFS was 8.6-38.0 months and 5-year DFS was 24.4% (10.0-60.5%). The median OS was 25.0-83.0 months and 5-year OS was 47.0% (15.0-87.5%). RPLND is a feasible treatment option with limited morbidity and possible oncological benefit for both synchronous and metachronous RPLNM in CRC. Further prospective clinical trials are required to establish a better evidence base for RPLND in the context of RPLNM in CRC and to understand the timing of RPLND in a multimodality pathway in order to optimise treatment outcomes for this group of patients.

12.
Ann Surg Oncol ; 30(4): 2266-2275, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36258058

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused unprecedented disruption to global healthcare delivery. In England, the majority of elective surgery was postponed or cancelled to increase intensive care capacity. Our unit instituted the 'RM Partners Cancer Hub' at the Royal Marsden Hospital in London, to deliver ongoing cancer surgery in a 'COVID-lite' setting. This article describes the operational set-up and outcomes for upper gastrointestinal (UGI) cancer resections performed during this period. METHODS: From April 2020 to April 2021, the Royal Marsden Hospital formed the RM Partners Cancer Hub. This approach was designed to coordinate resources and provide as much oncological treatment as feasible for patients across the RM Partners West London Cancer Alliance. A UGI surgical case prioritisation strategy, along with strict infection control pathways and pre-operative screening protocols, was adopted. RESULTS: A total of 231 patients underwent surgery for confirmed or suspected UGI cancer during the RM Partners Cancer Hub, with 213 completed resections and combined 90-day mortality rate of 3.5%. Good short-term survival outcomes were demonstrated with 2-year disease free survival (DFS) and overall survival (OS) for oesophageal (70.8% and 72.9%), gastric (66.7% and 83.3%) and pancreatic cancer resections (68.0% and 88.0%). One patient who developed perioperative COVID-19 during the RM Partners Cancer Hub operation made a full recovery with no lasting clinical sequelae. CONCLUSION: Our experience demonstrates that the RM Partners Cancer Hub approach is a safe strategy for continuing upper gastrointestinal (GI) resectional surgery during future periods of healthcare service disruption.


Assuntos
COVID-19 , Procedimentos Cirúrgicos do Sistema Digestório , Neoplasias , Humanos , Pandemias/prevenção & controle , Neoplasias/cirurgia , Reino Unido
13.
Eur Urol Oncol ; 5(5): 566-576, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35863988

RESUMO

BACKGROUND: Testicular cancer is a common malignancy among young males in western countries. OBJECTIVE: To examine the global disease burden and trends of testicular cancer incidence and mortality by age and country, and their associations with human development index (HDI), gross domestic product (GDP), lifestyle habits, and metabolic risk factors. DESIGN, SETTING, AND PARTICIPANTS: We retrieved the Global Cancer Observatory database for the testicular cancer incidence and mortality in 2020; the World Bank for GDP per capita; the United Nations for HDI; the WHO Global Health Observatory for prevalence of smoking and alcohol drinking; and the Cancer Incidence in Five Continents, WHO mortality database, Surveillance, Epidemiology, and End Results programme and Nordic Cancer Registries (NORDCAN) for trend analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We presented the testicular cancer incidence and mortality using age-standardised rates. We examined their associations with HDI, GDP, smoking, alcohol drinking, physical inactivity, overweight, obesity, and medical conditions including diabetes, hypertension, and hypercholesterolaemia by linear regression. We estimated the 10-yr trend of incidence and mortality by joinpoint regression with average annual percentage change with 95% confidence intervals in different age groups. RESULTS AND LIMITATIONS: There was a wide variation in the testicular cancer burden with the highest mortality found in low-income countries, and the regions of Central America and South America, while the highest incidence was observed in high-income countries, especially in Western and Northern Europe. We found a positive association for HDI, GDP, alcohol drinking, inactivity, overweight, obesity, and hypercholesterolaemia with testicular cancer incidence, while a negative correlation was observed between GDP and mortality of testicular cancer. Globally, there was an overall increasing incidence trend of testicular cancer for the past decade, particularly in younger males; the mortality trends of testicular cancer were relatively stable. However, we did not analyse the trend of different stages and subtypes of testicular cancer due to data unavailability. CONCLUSIONS: There was a global variation in the testicular cancer burden associated with HDI, GDP, alcohol drinking, inactivity, overweight, obesity, and hypercholesterolaemia. Testicular cancer had an increasing incidence but decreasing mortality. The increasing testicular cancer incidence in the younger population is of concern and calls for early detection and preventive interventions. PATIENT SUMMARY: Globally, testicular cancer incidence had been increasing particularly in the younger population, although its deaths rates had been decreasing. Socioeconomic indices, alcohol drinking, inactivity, overweight, obesity, and high plasma lipid levels are associated with testicular cancer incidence and mortality.


Assuntos
Hipercolesterolemia , Neoplasias Testiculares , Humanos , Incidência , Lipídeos , Masculino , Neoplasias Embrionárias de Células Germinativas , Obesidade , Sobrepeso , Fatores de Risco , Neoplasias Testiculares/epidemiologia
15.
Scott Med J ; 67(3): 126-128, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35509203

RESUMO

BACKGROUND AND AIMS: Testicular Germ Cell Tumours (TGCTs) are the commonest young adult male cancer, with excellent survival outcomes even with metastatic disease. Chemotherapy, radiotherapy, and surgery are international guideline-dictated standard of care (SOC) treatments for International Germ Cell Cancer Collaborative Group (IGCCCG) "good risk" TGCT, but are associated with significant toxicities. Therapy de-escalation aims to reduce treatment morbidity whilst preserving cure rates, and has been adopted by some centres for stage IIA/B seminoma. Here, we report on the contemporary UK treatment landscape for stage IIA/B seminoma. METHODS: A questionnaire-based survey of NHS England-designated specialist cancer centres hosting supra-regional specialist multi-disciplinary team (sMDT) services (n = 13) as well those within NHS Scotland, NHS Wales and Health and Social Care Northern Ireland. Respondents were asked to order preferences of SOC and therapy de-escalation treatments for stage IIA/B seminoma. RESULTS: We identified significant geographical heterogeneity in treatment preferences. Whilst up to a third of centres have adopted a treatment de-escalation regimen, the majority deliver combination chemotherapy or radiotherapy. CONCLUSION: A wider recognition of UK treatment heterogeneity and consideration of therapy de-escalation strategies at supra-regional sMDTs will increase stage IIA/B seminoma treatment options as part of clinical trials with oncological and quality of life endpoints.


Assuntos
Seminoma , Neoplasias Testiculares , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas , Qualidade de Vida , Seminoma/patologia , Seminoma/terapia , Neoplasias Testiculares/tratamento farmacológico , Reino Unido/epidemiologia , Adulto Jovem
16.
Biomedicines ; 10(4)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35453608

RESUMO

In December 2019, the first case of COVID-19 was reported and since then several groups have already published that the virus can be present in the testis. To study the influence of SARS-CoV-2 which cause a dysregulation of the androgen receptor (AR) level, thereby leading to fertility problems and inducing germ cell testicular changes in patients after the infection. Formalin-Fixed-Paraffin-Embedded (FFPE) testicular samples from patients who died with or as a result of COVID-19 (n = 32) with controls (n = 6), inflammatory changes (n = 9), seminoma with/without metastasis (n = 11) compared with healthy biopsy samples (n = 3) were analyzed and compared via qRT-PCR for the expression of miR-371a-3p. An immunohistochemical analysis (IHC) and ELISA were performed in order to highlight the miR-371a-3p targeting the AR. Serum samples of patients with mild or severe COVID-19 symptoms (n = 34) were analyzed for miR-371a-3p expression. In 70% of the analyzed postmortem testicular tissue samples, a significant upregulation of the miR-371a-3p was detected, and 75% of the samples showed a reduced spermatogenesis. In serum samples, the upregulation of the miR-371a-3p was also detectable. The upregulation of the miR-371a-3p is responsible for the downregulation of the AR in SARS-CoV-2-positive patients, resulting in decreased spermatogenesis. Since the dysregulation of the AR is associated with infertility, further studies have to confirm if the identified dysregulation is regressive after a declining infection.

17.
World J Urol ; 40(6): 1505-1512, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35279732

RESUMO

PURPOSE: To describe the perioperative safety, functional and immediate post-operative oncological outcomes of minimally invasive RPLND (miRPLND) for testis cancer. METHODS: We performed a retrospective multi-centre cohort study on testis cancer patients treated with miRPLND from 16 institutions in eight countries. We measured clinician-reported outcomes stratified by indication. We performed logistic regression to identify predictors for maintained postoperative ejaculatory function. RESULTS: Data for 457 men undergoing miRPLND were studied. miRPLND comprised laparoscopic (n = 56) or robotic (n = 401) miRPLND. Indications included pre-chemotherapy in 305 and post-chemotherapy in 152 men. The median retroperitoneal mass size was 32 mm and operative time 270 min. Intraoperative complications occurred in 20 (4%) and postoperative complications in 26 (6%). In multivariable regression, nerve sparing, and template resection improved ejaculatory function significantly (template vs bilateral resection [odds ratio (OR) 19.4, 95% confidence interval (CI) 6.5-75.6], nerve sparing vs non-nerve sparing [OR 5.9, 95% CI 2.3-16.1]). In 91 men treated with primary RPLND, nerve sparing and template resection, normal postoperative ejaculation was reported in 96%. During a median follow-up of 33 months, relapse was detected in 39 (9%) of which one with port site (< 1%), one with peritoneal recurrence and 10 (2%) with retroperitoneum recurrences. CONCLUSION: The low proportion of complications or peritoneal recurrences and high proportion of men with normal postoperative ejaculatory function supports further miRPLND studies.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Estudos de Coortes , Estudos de Viabilidade , Humanos , Excisão de Linfonodo/efeitos adversos , Masculino , Recidiva Local de Neoplasia/cirurgia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Espaço Retroperitoneal/cirurgia , Estudos Retrospectivos , Neoplasias Testiculares/patologia , Resultado do Tratamento
19.
Nat Ecol Evol ; 6(1): 88-102, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34949820

RESUMO

Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant clonal dynamics remain limited. We investigated spatial and temporal features of clonal diversification in clear cell renal cell carcinoma through a combination of modelling and real tumour analysis. We observe that the mode of tumour growth, surface or volume, impacts the extent of subclonal diversification, enabling interpretation of clonal diversity in patient tumours. Specific patterns of proliferation and necrosis explain clonal expansion and emergence of parallel evolution and microdiversity in tumours. In silico time-course studies reveal the appearance of budding structures before detectable subclonal diversification. Intriguingly, we observe radiological evidence of budding structures in early-stage clear cell renal cell carcinoma, indicating that future clonal evolution may be predictable from imaging. Our findings offer a window into the temporal and spatial features of clinically relevant clonal evolution.


Assuntos
Neoplasias , Evolução Clonal , Humanos
20.
Eur Urol Open Sci ; 33: 83-88, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34723218

RESUMO

BACKGROUND: Retroperitoneal lymph node dissection (RPLND) is essential for the treatment of metastatic germ cell tumours of the testis. Recommendations on the referral and management of complex urological cancers in the UK includes centralisation of services to regional centres. OBJECTIVE: To review contemporary PC-RPLND outcomes at a high-volume centre with a complex case-mix, and compare with national registry data. DESIGN SETTING AND PARTICIPANTS: We retrospectively reviewed the medical records of PC-RPLNDs performed for germ cell tumours at our centre between July 2012 and September 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were Clavien 3+ complications, histology, rates of positive margin, relapse, in-field recurrences, and mortality. Secondary outcomes were blood loss, operation time, blood transfusion, adjuvant procedures, length of stay, and lymph node count. Surgical and histological outcomes of all RPLNDs for testicular cancers were compared with national RPLND registry data. For statistical difference, χ2 testing was used. RESULTS AND LIMITATIONS: A total of 178 procedures were performed, including 31 (17%) redo RPLNDs. Clavien 3+ complications occurred in 11 (7%). Histological findings in non-redo cases were the following: necrosis 24%, teratoma 62%, viable germ cell tumour 11%, and dedifferentiated cancers 3%. Rates of positive margin, relapse, and in-field recurrence were 11%, 17%, and 2%, respectively. Overall survival was 89% at a median of 36 mo. The median blood loss was 650 ml (350, 1250), with a transfusion rate of 8%. Nephrectomy, vascular reconstruction, and visceral resection was required in 12%, 6%, and 3% respectively. The median inpatient stay was 6 d (5, 8) and the median node count was 35 (20, 37). A comparison of all RPLNDs with national data showed no statistical difference in primary outcomes. Our blood transfusion rate was significantly lower (12% vs 21%, χ2 [1, N = 322] = 4.296, p = 0.038). CONCLUSIONS: Centralisation led to high quality of RPLND in UK. Within that, our series (the largest in the UK) demonstrates no significant difference in outcomes despite higher complexity cases. Our blood transfusion rates are in fact lower than national figures. Complex RPLNDs should be performed in high-volume centres where possible. PATIENT SUMMARY: In the UK, retroperitoneal lymph node dissections (RPLND) are centralised to specialist centres and the quality of surgery is high, with low complications and good histological outcomes. When compared to national data, we found no significant difference in the majority of outcomes from our high-volume centre despite our complex case-mix.

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