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2.
BMC Med Educ ; 24(1): 767, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014422

RESUMO

BACKGROUND: Comprehensive cancer care requires effective collaboration by interprofessional healthcare teams. The need to develop educational initiatives to improve interprofessional collaboration is increasingly recognised. However, there is no agreement regarding the interprofessional competencies required for effective cancer care leading to much variation on the focus of research, planning and managing change. A scoping review was conducted to identify the current status of IPE in cancer care and to summarise the results of previous research in order to guide the development of interprofessional education in cancer care. METHODS: The JBI Scoping Review guidelines were used to guide the process of the review. A search of the available literature was conducted in CINAHL, MEDLINE (Ovid), PubMed, PsycInfo, Scopus databases from January 2012 to March 2023 to investigate IPE for health professional clinicians working in cancer care. RESULTS: Of the 825 initial references and 153 studies imported for screening, a total of 28 studies were included in the final review. From those studies, seven focused on the need for IPE and interprofessional competence for oncology healthcare professionals, four reviewed existing IPE programs and 17 described the development and evaluation of interprofessional education. Findings show variation and lack of concept definitions underpinning research in IPE in cancer care settings. Variation also exists in the range of research activities in IPE, most notably related to communication, teamwork and the development of interprofessional practice. The evaluation of impact of IPE is mainly focused on health care professionals' self-evaluation and general feedback. Impact on patient care was only evaluated in one study. CONCLUSIONS: Based on the results, interprofessional education research in the field of cancer care is limited in Europe. Thus, there is a significant increase in publications in the last five years. A more systematic focus on the theoretical framework and definition of concepts would be of value. Research and programme development should be based on a shared understanding on what constitutes the interprofessional competences and IPE. Programmes to develop interprofessional practice should be developed and implemented systematically with inclusion of validated assessment methods, and evaluated and improved regularly.


Assuntos
Relações Interprofissionais , Neoplasias , Equipe de Assistência ao Paciente , Humanos , Neoplasias/terapia , Educação Interprofissional , Oncologia/educação , Pessoal de Saúde/educação , Comportamento Cooperativo
3.
BJS Open ; 8(3)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38747103

RESUMO

BACKGROUND: Neoadjuvant therapy has an established role in the treatment of patients with colorectal cancer. However, its role continues to evolve due to both advances in the available treatment modalities, and refinements in the indications for neoadjuvant treatment and subsequent surgery. METHODS: A narrative review of the most recent relevant literature was conducted. RESULTS: Short-course radiotherapy and long-course chemoradiotherapy have an established role in improving local but not systemic disease control in patients with rectal cancer. Total neoadjuvant therapy offers advantages over short-course radiotherapy and long-course chemoradiotherapy, not only in terms of increased local response but also in reducing the risk of systemic relapses. Non-operative management is increasingly preferred to surgery in patients with rectal cancer and clinical complete responses but is still associated with some negative impacts on functional outcomes. Neoadjuvant chemotherapy may be of some benefit in patients with locally advanced colon cancer with proficient mismatch repair, although patient selection is a major challenge. Neoadjuvant immunotherapy in patients with deficient mismatch repair cancers in the colon or rectum is altering the treatment paradigm for these patients. CONCLUSION: Neoadjuvant treatments for patients with colon or rectal cancers continue to evolve, increasing the complexity of decision-making for patients and clinicians alike. This review describes the current guidance and most recent developments.


Assuntos
Neoplasias Colorretais , Terapia Neoadjuvante , Humanos , Neoplasias Colorretais/terapia , Imunoterapia/métodos , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Quimiorradioterapia/métodos
4.
J Clin Oncol ; 42(2): 146-156, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37906724

RESUMO

PURPOSE: In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are still being debated. This randomized, controlled, open-label, multicenter phase III trial (EudraCT 2006-006088-22; ClinicalTrials.gov identifier: NCT02158988) explored the impact on overall survival (OS) of HIPEC after CRS. PATIENTS AND METHODS: Adult patients with GC and histologically proven PM were randomly assigned (1:1) to perioperative chemotherapy and CRS alone (CRS-A) or CRS plus HIPEC (CRS + H). HIPEC comprised mitomycin C 15 mg/m2 and cisplatin 75 mg/m2 in 5 L of saline perfused for 60 minutes at 42°C. The primary end point was OS; secondary endpoints included progression-free survival (PFS), other distant metastasis-free survival (MFS), and safety. Analyses followed the intention-to-treat principle. RESULTS: Between March 2014 and June 2018, 105 patients were randomly assigned (53 patients to CRS-A and 52 patients to CRS + H). The trial stopped prematurely because of slow recruitment. In 55 patients, treatment stopped before CRS mainly due to disease progression/death. Median OS was the same for both groups (CRS + H, 14.9 [97.2% CI, 8.7 to 17.7] months v CRS-A, 14.9 [97.2% CI, 7.0 to 19.4] months; P = .1647). The PFS was 3.5 months (95% CI, 3.0 to 7.0) in the CRS-A group and 7.1 months (95% CI, 3.7 to 10.5; P = .047) in the CRS + H group. The CRS + H group showed better MFS (10.2 months [95% CI, 7.7 to 14.7] v CRS-A, 9.2 months [95% CI, 6.8 to 11.5]; P = .0286). The incidence of grade ≥3 adverse events (AEs) was similar between groups (CRS-A, 38.1% v CRS + H, 43.6%; P = .79). CONCLUSION: This study showed no OS difference between CRS + H and CRS-A. PFS and MFS were significantly better in the CRS + H group, which needs further exploration. HIPEC did not increase AEs.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Gástricas , Adulto , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Taxa de Sobrevida , Estudos Retrospectivos
5.
Eur J Surg Oncol ; 49(9): 106989, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37556988

RESUMO

INTRODUCTION: Multidisciplinary and multi-professional collaboration is vital in providing better outcomes for patients The aim of the INTERACT-EUROPE Project (Wide Ranging Cooperation and Cutting Edge Innovation As A Response To Cancer Training Needs) was to develop an inter-specialty curriculum. A pilot project will enable a pioneer cohort to acquire a sample of the competencies needed. METHODS: A scoping review, qualitative and quantitative surveys were undertaken. The quantitative survey results are reported here. Respondents, including members of education boards, curriculum committees, trainee committees of European specialist societies and the ECO Patient Advisory Committee, were asked to score 127 proposed competencies on a 7-point Likert scale as to their value in achieving the aims of the curriculum. Results were discussed and competencies developed at two stakeholder meetings. A consultative document, shared with stakeholders and available online, requested views regarding the other components of the curriculum. RESULTS: Eleven competencies were revised, three omitted and three added. The competencies were organised according to the CanMEDS framework with 13 Entrustable Professional Activities, 23 competencies and 127 enabling competencies covering all roles in the framework. Recommendations regarding the infrastructure, organisational aspects, eligibility of trainees and training centres, programme contents, assessment and evaluation were developed using the replies to the consultative document. CONCLUSIONS: An Inter-specialty Cancer Training Programme Curriculum and a pilot programme with virtual and face-to-face components have been developed with the aim of improving the care of people affected by cancer.


Assuntos
Competência Clínica , Neoplasias , Humanos , Projetos Piloto , Currículo , Europa (Continente) , Neoplasias/terapia
6.
Eur J Surg Oncol ; 49(9): 107000, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37549561

RESUMO

Despite the importance of diversity for the success and survival of biological and social systems, women are underrepresented in leadership positions, particularly in the medical field. Data from seven internationally renowned academic associations in surgical, medical, and radiation oncology show that women's representation in leadership roles is only 11%, with no individual society exceeding 20%. Possible justifications for the underrepresentation of women include unconscious biases and societal norms. Fortunately, a notable development in the form of an increased number of women attaining leadership positions in many major professional societies has emerged over recent times, thereby reflecting a positive transformation in the direction of gender equality. The authors recommend organizational interventions such as mentorship, leadership development programs, and national-level initiatives with global collaboration. The oncology community must promote a culture of cooperation and gender equality to ensure equitable opportunities for women in all aspects of life, including professional hierarchy.


Assuntos
Liderança , Oncologia , Humanos , Feminino
7.
Eur J Surg Oncol ; 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37429796

RESUMO

INTRODUCTION: Malnutrition is common in patients suffering from malignant diseases and has a major impact on patient outcomes. Prevention and early detection are crucial for effective treatment. This study aimed to investigate current international practice in the assessment and management of malnutrition in surgical oncology departments. MATERIAL AND METHODS: The survey was designed by European Society of Surgical Oncology (ESSO) and ESSO Young Surgeons and Alumni Club (EYSAC) Research Academy as an online questionnaire with 41 questions addressing three main areas: participant demographics, malnutrition assessment, and perioperative nutritional standards. The survey was distributed from October to November 2021 via emails, social media and the ESSO website to surgical networks focussing on surgical oncologists. Results were collected and analysed by an independent team. RESULTS: A total of 156 participants from 39 different countries answered the survey, reflecting a response rate of 1.4%. Surgeons reported treating a mean of 22.4 patients per month. 38% of all patients treated in surgical oncology departments were routinely screened for malnutrition. 52% of patients were perceived as being at risk for malnutrition. The most used screening tool was the "Malnutrition Universal Screening Tool" (MUST). 68% of participants agreed that the surgeon is responsible for assessing preoperative nutritional status. 49% of patients were routinely seen by dieticians. In cases of severe malnutrition, 56% considered postponing the operation. CONCLUSIONS: The reported rate of malnutrition screening by surgical oncologists is lower than expected (38%). This indicates a need for improved awareness of malnutrition in surgical oncology, and nutritional screening.

8.
Indian J Surg Oncol ; 14(Suppl 1): 97-105, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37359943

RESUMO

Malignant mesotheliomas most often affect the pleura and tend to spread locally within the originating cavity. Mesotheliomas are already rare diseases, and cases with synchronous pleural and peritoneal involvement are scarce in the literature. Mesothelioma in children is a rare disease representing only 0.9% of all mesotheliomas. They exhibit similar distribution and characteristics as mesotheliomas in adults and generally, a poor prognosis. Due to the rarity, there is no standardized treatment recommendation for children with mesothelioma. Though the malignant mesothelioma tends to spread locally within the originating cavity, pleuM have been reported to metastasize into the peritoneal cavity and vice versa. As there are only few studies concerning the metastatic spread of mesothelioma, it is difficult to define a precise incidence and risk factors for patients to develop metastases of the other mesothelium. There is no standardized therapeutic recommendation for patients with synchronous pleuM and perM. Our patient proved to profit from a radical two-stage surgical approach in combination with locoregional chemotherapy; she showed no sign of tumor recurrences 9 years after tumor resection. In conclusion, clinical studies are needed to confirm the benefit of this treatment and to determine its limitations and selection criteria.

9.
Langenbecks Arch Surg ; 408(1): 207, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37222835

RESUMO

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) is accompanied with an increased risk of acute kidney injury (AKI). Whether AKI is induced by chemotoxicity or hyperthermia-related changes in renal perfusion remains controversial. The influence of HIPEC on renal perfusion has not been evaluated in patients yet. METHODS: Renal blood perfusion was assessed in ten patients treated with HIPEC by intraoperative renal Doppler pulse-wave ultrasound. Ultrasound (US) examinations were performed pre-, intra-, and postoperative with analyses of time-velocity curves. Patient demographics, surgical details, and data regarding renal function were recorded perioperatively. For evaluation of renal Doppler US to predict AKI, patients were divided in two groups with (AKI +) and without (AKI -) kidney injury. RESULTS: Throughout HIPEC perfusion, neither significant nor consistent changes in renal perfusion could be observed. Postoperative AKI occurred in 6 of 10 participating patients. Intraoperative renal resistive index (RRI) values > 0.8 were observed in one patient developing stage 3 AKI according KDIGO criteria. At 30 min in perfusion, RRI values were significantly higher in AKI + patients. CONCLUSION: AKI is a common and frequent complication after HIPEC, but underlying pathophysiology remains elusive. High intraoperative RRI values may indicate an increased risk of postoperative AKI. Present data challenges the relevance of hyperthermia-derived hypothesis of renal hypoperfusion with prerenal injury during HIPEC. More attention should be drawn towards chemotoxic-induced hypothesis of HIPEC-induced AKI and caution applying regimens containing nephrotoxic agents in patients. Further confirmatory and complementary studies on renal perfusion as well as pharmacokinetic HIPEC studies are required.


Assuntos
Injúria Renal Aguda , Quimioterapia Intraperitoneal Hipertérmica , Humanos , Rim/fisiologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Perfusão , Angiografia
11.
Pleura Peritoneum ; 8(1): 1-9, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37020469

RESUMO

Objectives: Pseudomyxoma peritonei (PMP) is a rare cancer currently affecting over 11,736 patients across Europe. Since PMP is so uncommon, collaboration between scientific centers is key to discovering the mechanisms behind the disease, efficient treatments, and targets pointing to a cure. To date, no consensus has been reached on the minimum data that should be collected during PMP research studies. This issue has become more important as biobanking becomes the norm. This paper begins the discussion around a minimum data set that should be collected by researchers through a review of available clinical trial reports in order to facilitate collaborative efforts within the PMP research community. Content: A review of articles from PubMed, CenterWatch, ClinicalTrials.gov and MedRxiv was undertaken, and clinical trials reporting PMP results selected. Summary: There is a core set of data that researchers report, including age and sex, overall survival, peritoneal cancer index (PCI) score, and completeness of cytoreduction, but after this, reports become variable. Outlook: Since PMP is a rare disease, it is important that reports include as large of a number of standardised data points as possible. Our research indicates that there is still much ground to cover before this becomes a reality.

12.
PLoS One ; 18(3): e0275883, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36972259

RESUMO

Laser therapeutic applications, such as the use of high energy lasers (HILT), are widely used in physical therapy, but basic studies on the mechanisms of action of HILT on tendinous/ligamentous tissue are largely lacking. The aim of this study was to investigate microcirculatory changes of the patellar tendon by HILT. 21 healthy volunteers were included in the present investigation. Before and after HILT, as well as 10 minutes later, the microcirculation was measured by noninvasive laser Doppler and white light spectroscopy (O2C device). Tissue temperature was recorded at the measurement time points using thermography. Blood flow increased significantly by 86.38 arbitrary units (AU; p < 0.001) after the intervention and by 25.76 AU (p < 0.001) at follow-up. Oxygen saturation increased by 20.14% (p < 0.001) and 13.48%, respectively (p < 0.001), whereas relative hemoglobin decreased by 6.67 AU and 7.90 AU, respectively. Tendon temperature increased by 9.45° and 1.94° Celsius, respectively. Acceleration of blood flow by improving the flow properties of erythrocytes and platelets may have caused the results. HILT could be a therapeutic perspective for tendon pathologies with impaired microcirculation, although further studies are needed to validate the experimental results.


Assuntos
Tendão do Calcâneo , Terapia a Laser , Ligamento Patelar , Humanos , Microcirculação/fisiologia , Crioterapia , Fluxometria por Laser-Doppler/métodos
13.
Sci Rep ; 13(1): 815, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646734

RESUMO

Changes in the mechanical properties (i.e., stiffness) of soft tissues have been linked to musculoskeletal disorders, pain conditions, and cancer biology, leading to a rising demand for diagnostic methods. Despite the general availability of different stiffness measurement tools, it is unclear as to which are best suited for different tissue types and the related measurement depths. The study aimed to compare different stiffness measurement tools' (SMT) reliability on a multi-layered phantom tissue model (MPTM). A polyurethane MPTM simulated the four layers of the thoracolumbar region: cutis (CUT), subcutaneous connective tissue (SCT), fascia profunda (FPR), and erector spinae (ERS), with varying stiffness parameters. Evaluated stiffness measurement tools included Shore Durometer, Semi-Electronic Tissue Compliance Meter (STCM), IndentoPRO, MyotonPRO, and ultrasound imaging. Measurements were made by two independent, blinded examiners. Shore Durometer, STCM, IndentoPRO, and MyotonPRO reliably detected stiffness changes in three of the four MPTM layers, but not in the thin (1 mm thick) layer simulating FPR. With ultrasound imaging, only stiffness changes in layers thicker than 3 mm could be measured reliably. Significant correlations ranging from 0.70 to 0.98 (all p < 0.01) were found. The interrater reliability ranged from good to excellent (ICC(2,2) = 0.75-0.98). The results are encouraging for researchers and clinical practitioners as the investigated stiffness measurement tools are easy-to-use and comparatively affordable.


Assuntos
Músculo Esquelético , Coluna Vertebral , Fáscia , Imagens de Fantasmas , Reprodutibilidade dos Testes , Pele , Ultrassonografia
14.
Front Oncol ; 12: 864647, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719946

RESUMO

The treatment of patients with peritoneal metastasis from gastric cancer continues to evolve. With various forms of intraperitoneal drug delivery available, it is now possible to reach the sites of peritoneal metastases, which were otherwise sub-optimally covered by systemic chemotherapy, owing to the blood peritoneal barrier. We conducted a narrative review based on an extensive literature research, highlighting the current available intraperitoneal treatment options, which resulted in improved survival in well-selected patients of peritoneally metastasized gastric cancer. Intraperitoneal chemotherapy showed promising results in four different treatment modalities: prophylactic, neoadjuvant, adjuvant, and palliative. It is now possible to choose the type of intraperitoneal treatment/s in combination with systemic treatment/s, depending on patients' general condition and peritoneal disease burden, thus providing individualized treatment to these patients. Randomized controlled trials for the different treatment modalities were mainly conducted in Asia and lack further validation in the other parts of the world. Most recent application tools, such as pressurized intraperitoneal aerosol chemotherapy, seem promising and need to pass the ongoing clinical trials.

15.
Visc Med ; 38(2): 90-98, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35614892

RESUMO

Background: The survival prognosis of patients with peritoneal metastasis (PM) of gastrointestinal (GI) cancer is generally poor and treatment consists of, according to international guidelines, systemic chemotherapy. A multimodal treatment approach, including cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy, not only proved to be beneficial mainly in colorectal cancer, but also in selected patients with gastric cancer. The authors performed systematic research of articles and ongoing clinical trials using the keywords "PIPAC" and "gastric cancer" or "colorectal cancer" in PubMed in October 2021. Key findings, such as complications rates, treatment protocols, and overall survival were summarized and illustrated in Tables and critically discussed. Summary: Twenty years ago, the technique of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) was developed by Reymond et al. and delivered evidence to be recognized as a basic therapeutic tool in this multimodal therapy. Currently, there are several ongoing Phase II and III trials exploring the usage and efficacy of PIPAC as a neoadjuvant, adjuvant, or palliative component of treatment in patients with PM of GI cancer. Key Messages: The aim of this narrative review was to help navigate the reader throughout the most current evidence for the use PIPAC and to highlight its indication in patients with upper and lower GI cancer with PM. It also provides an outline of ongoing studies and future perspectives.

16.
Surg Endosc ; 36(6): 3708-3720, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35246738

RESUMO

BACKGROUND: The outcomes of endoscopic ultrasonography-guided drainage (EUSD) in treatment of pancreas fluid collection (PFC) after pancreas surgeries have not been evaluated systematically. The current systematic review and meta-analysis aim to evaluate the outcomes of EUSD in patients with PFC after pancreas surgery and compare it with percutaneous drainage (PCD). METHODS: PubMed and Web of Science databases were searched for studies reporting outcomes EUSD in treatment of PFC after pancreas surgeries, from their inception until January 2022. Two meta-analyses were performed: (A) a systematic review and single-arm meta-analysis of EUSD (meta-analysis A) and (B) two-arm meta-analysis comparing the outcomes of EUSD and PCD (meta-analysis B). Pooled proportion of the outcomes in meta-analysis A as well as odds ratio (OR) and mean difference (MD) in meta-analysis B was calculated to determine the technical and clinical success rates, complications rate, hospital stay, and recurrence rate. ROBINS-I tool was used to assess the risk of bias. RESULTS: The literature search retrieved 610 articles, 25 of which were eligible for inclusion. Included clinical studies comprised reports on 695 patients. Twenty-five studies (477 patients) were included in meta-analysis A and eight studies (356 patients) were included in meta-analysis B. In meta-analysis A, the technical and clinical success rates of EUSD were 94% and 87%, respectively, with post-procedural complications of 14% and recurrence rates of 9%. Meta-analysis B showed comparable technical and clinical success rates as well as complications rates between EUSD and PCD. EUSD showed significantly shorter duration of hospital stay compared to that of patients treated with PCD. CONCLUSION: EUSD seems to be associated with high technical and clinical success rates, with low rates of procedure-related complications. Although EUSD leads to shorter hospital stay compared to PCD, the certainty of evidence was low in this regard.


Assuntos
Endossonografia , Pancreatopatias , Drenagem , Humanos , Tempo de Internação , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Pancreatopatias/cirurgia
17.
Eur J Surg Oncol ; 48(11): 2338-2345, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35090797

RESUMO

INTRODUCTION: Multimodal treatment of patients with advanced pelvic malignancies (APM) is challenging and surgical expertise is usually concentrated in highly specialised centres. Given significant regional variation in APM surgery, surgical training represents a cornerstone in standardising and future-proofing of this complex therapy. The aim of this study was to describe the availability and current satisfaction levels with surgical training for APM. MATERIAL AND METHODS: An online questionnaire was developed and distributed through the Redcap© platform with 32 questions addressing participant and institution demographics, and training in APM surgeries. The survey was electronically disseminated in 2021 to surgical networks across Europe including all specialities treating APM via the European Society of Surgical Oncology (ESSO). All statistical analysis were performed using R. RESULTS: The survey received 280 responses from surgeons across 49 countries, representing general surgery (36%), surgical oncology (30%), gynaeoncology (15%), colorectal surgery (14%) and urology (5%). Fifty-three percent of participants report performing >25 APM procedures/year. Respondents were departmental chiefs (12%), consultants (34%), specialist surgeons (40%) and fellows (15%). 34% were happy/very happy with their training with 70% satisfaction about their exposure to surgical procedures. Respondents reported a lack of standardised training (72%), monitoring tools (41%) and mentorship (56%). 57% rated attended courses as useful for training, while 80% rated visiting expert centres as useful. CONCLUSION: This study has identified a learning need for improved structured training in APM, with low current satisfaction levels with exposure to APM training. Organisations such as ESSO provide an important platform for visiting expert centres, courses, and structured training.


Assuntos
Neoplasias Pélvicas , Cirurgiões , Oncologia Cirúrgica , Urologia , Humanos , Neoplasias Pélvicas/cirurgia , Europa (Continente) , Urologia/educação , Oncologia Cirúrgica/educação , Inquéritos e Questionários
18.
Blood Adv ; 6(7): 2195-2206, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-34861679

RESUMO

Deregulation such as overexpression of adhesion molecules influences cancer progression and survival. Metastasis of malignant cells from their primary tumor site to distant organs is the most common reason for cancer-related deaths. Junctional adhesion molecule-C (JAM-C), a member of the immunoglobulin-like JAM family, can homodimerize and aid cancer cell migration and metastasis. Here we show that this molecule is dynamically expressed on multiple myeloma (MM) cells in the bone marrow and co-localizes with blood vessels within the bone marrow of patients and mice. In addition, upregulation of JAM-C inversely correlates with the downregulation of the canonical plasma cell marker CD138 (syndecan-1), whose surface expression has recently been found to dynamically regulate a switch between MM growth in situ and MM dissemination. Moreover, targeting JAM-C in a syngeneic in vivo MM model ameliorates MM progression and improves outcome. Overall, our data demonstrate that JAM-C might serve not only as an additional novel diagnostic biomarker but also as a therapeutic target in MM disease.


Assuntos
Moléculas de Adesão Celular/metabolismo , Molécula C de Adesão Juncional , Mieloma Múltiplo , Receptores de Superfície Celular/metabolismo , Animais , Medula Óssea/patologia , Moléculas de Adesão Celular/genética , Movimento Celular , Humanos , Camundongos , Mieloma Múltiplo/tratamento farmacológico
19.
Leukemia ; 36(3): 790-800, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34584204

RESUMO

Multiple myeloma remains a largely incurable disease of clonally expanding malignant plasma cells. The bone marrow microenvironment harbors treatment-resistant myeloma cells, which eventually lead to disease relapse in patients. In the bone marrow, CD4+FoxP3+ regulatory T cells (Tregs) are highly abundant amongst CD4+ T cells providing an immune protective niche for different long-living cell populations, e.g., hematopoietic stem cells. Here, we addressed the functional role of Tregs in multiple myeloma dissemination to bone marrow compartments and disease progression. To investigate the immune regulation of multiple myeloma, we utilized syngeneic immunocompetent murine multiple myeloma models in two different genetic backgrounds. Analyzing the spatial immune architecture of multiple myeloma revealed that the bone marrow Tregs accumulated in the vicinity of malignant plasma cells and displayed an activated phenotype. In vivo Treg depletion prevented multiple myeloma dissemination in both models. Importantly, short-term in vivo depletion of Tregs in mice with established multiple myeloma evoked a potent CD8 T cell- and NK cell-mediated immune response resulting in complete and stable remission. Conclusively, this preclinical in-vivo study suggests that Tregs are an attractive target for the treatment of multiple myeloma.


Assuntos
Mieloma Múltiplo/imunologia , Linfócitos T Reguladores/imunologia , Animais , Medula Óssea/imunologia , Progressão da Doença , Humanos , Ativação Linfocitária , Camundongos , Microambiente Tumoral
20.
Ann Surg Oncol ; 29(1): 152-162, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34350529

RESUMO

BACKGROUND: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) represents a multimodal treatment concept for patients with peritoneal surface malignancies. The use of intraperitoneal cisplatin (CDDP) is associated with a risk of acute kidney injury (AKI). The aim of this study is to evaluate the protective effect of perioperative sodium thiosulfate (STS) administration on kidney function in patients undergoing CRS and CDDP-based HIPEC. PATIENTS AND METHODS: We retrospectively analyzed clinical data of all patients who underwent CRS and CDDP-based HIPEC at our hospital between March 2017 and August 2020. Patients were stratified according to the use of sodium thiosulfate (STS vs. no STS). We compared kidney function and clinical outcome parameters between both groups and determined risk factors for postoperative AKI on univariate and multivariate analysis. AKI was classified according to acute kidney injury network (AKIN) criteria. RESULTS: Of 238 patients who underwent CRS and CDDP-based HIPEC, 46 patients received STS and 192 patients did not. There were no significant differences in baseline characteristics. In patients who received STS, a lower incidence (6.5% vs. 30.7%; p = 0.001) and severity of AKI (p = 0.009) were observed. On multivariate analysis, the use of STS (OR 0.089, p = 0.001) remained an independent kidney-protective factor, while arterial hypertension (OR 5.283, p < 0.001) and elevated preoperative urea serum level (OR 5.278, p = 0.032) were predictors for postoperative AKI. CONCLUSIONS: The present data suggest that STS protects patients from AKI caused by CRS and CDDP-based HIPEC. Further prospective studies are needed to validate the benefit of STS among kidney-protective strategies.


Assuntos
Injúria Renal Aguda , Cisplatino , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Cisplatino/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Estudos Retrospectivos , Tiossulfatos
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