To make recommendations on managing the surveillance of patients with stage I, II, III or resectable IV melanoma who are clinically free of disease following treatment with curative intent.
This ...guideline was developed by Ontario Health's (Cancer Care Ontario's) Program in Evidence-Based Care and the Melanoma Disease Site Group (including seven medical oncologists, four surgical oncologists, three dermatologists, one radiation oncologist and one patient representative). The MEDLINE, EMBASE, Cochrane Library, PROSPERO databases and the main relevant guideline websites were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Melanoma Disease Site Group. The Grading of Recommendations, Assessment, Development and Evaluation approach was followed, and the Modified Delphi method was used.
Based on the current evidence (eight eligible original study papers and four relevant guidelines) and the clinical opinions of the authors of this guideline, the initial recommendations were made. To reach 75% agreement for each recommendation, the Melanoma Disease Site Group (16 members) voted twice and one recommendation was voted on three times. After a comprehensive internal and external review process (including national and international reviewers), 12 recommendations, three weak recommendations and six qualified statements were ultimately made.
After a systematic review, a comprehensive internal and external review process and a consensus process, the current guideline has been created. The guideline authors believe that this guideline will help clinicians, patients and policymakers make well-informed healthcare decisions that will guide them in clinical melanoma surveillance and ultimately assist in improving patient outcomes.
For patients who are diagnosed with early-stage cutaneous melanoma, the principal therapy is wide surgical excision of the primary tumour and assessment of lymph nodes. The purpose of the present ...guideline was to update the 2010 Cancer Care Ontario guideline on wide local excision margins and sentinel lymph node biopsy (slnb), including treatment of the positive sentinel node, for melanomas of the trunk, extremities, and head and neck.
Using Ovid, the medline and embase electronic databases were systematically searched for systematic reviews and primary literature evaluating narrow compared with wide excision margins and the use of slnb for melanoma of the truck and extremities and of the head and neck. Search timelines ran from 2010 through week 25 of 2017.
Four systematic reviews were chosen for inclusion in the evidence base. Where systematic reviews were available, the search of the primary literature was conducted starting from the end date of the search in the reviews. Where systematic reviews were absent, the search for primary literature ran from 2010 forward. Of 1213 primary studies identified, 8 met the inclusion criteria. Two randomized controlled trials were used to inform the recommendation on completion lymph node dissection.Key updated recommendations include:■ Wide local excision margins should be 2 cm for melanomas of the trunk, extremities, and head and neck that exceed 2 mm in depth.■ slnb should be offered to patients with melanomas of the trunk, extremities, and head and neck that exceed 0.8 mm in depth.■ Patients with sentinel node metastasis should be considered for nodal observation with ultrasonography rather than for completion lymph node dissection.
Recommendations for primary excision margins, sentinel lymph node biopsy, and completion lymph node dissection in patients with cutaneous melanoma have been updated based on the current literature.
The purpose of this guideline is to provide guidance on appropriate management of satellite and in-transit metastasis (itm) from melanoma.
The guideline was developed by the Program in Evidence-Based ...Care (pebc) of Ontario Health (Cancer Care Ontario) and the Melanoma Disease Site Group. Recommendations were drafted by a Working Group based on a systematic review of publications in the medline and embase databases. The document underwent patient- and caregiver-specific consultation and was circulated to the Melanoma Disease Site Group and the pebc Report Approval Panel for internal review; the revised document underwent external review.
"Minimal itm" is defined as lesions in a location with limited spread (generally 1-4 lesions); the lesions are generally superficial, often clustered together, and surgically resectable. "Moderate itm" is defined as more than 5 lesions covering a wider area, or the rapid development (within weeks) of new in-transit lesions. "Maximal itm" is defined as large-volume disease with multiple (>15-20) 2-3 cm nodules or subcutaneous or deeper lesions over a wide area.■ In patients presenting with minimal itm, complete surgical excision with negative pathologic margins is recommended. In addition to complete surgical resection, adjuvant treatment may be considered.■ In patients presenting with moderate unresectable itm, consider using this approach for localized treatment: intralesional interleukin 2 or talimogene laherparepvec as 1st choice, topical diphenylcyclopropenone as 2nd choice, or radiation therapy as 3rd choice. Evidence is insufficient to recommend intralesional bacille Calmette- Guérin or CO
laser ablation outside of a research setting.■ In patients presenting with maximal itm confined to an extremity, isolated limb perfusion, isolated limb infusion, or systemic therapy may be considered. In extremely select cases, amputation could be considered as a final option in patients without systemic disease after discussion at a multidisciplinary case conference.■ In cases in which local, regional, or surgical treatments for itm might be ineffective or unable to be performed, or if a patient has systemic metastases at the same time, systemic therapy may be considered.
Clinical Vignette: A 50-year-old woman presents to the emergency department with increasing abdominal pain. Abdominal computed tomography imaging reveals an expanded inferior vena cava-filling defect ...that is suspicious for a retroperitoneal sarcoma, possibly a primary leiomyosarcoma of the inferior vena cava. The surgery team discusses the case with the radiologist, and all agree that there are multiple challenges with obtaining a tissue diagnosis and determining resectability. Thus, it is decided that this patient should be discussed at a multidisciplinary case conference. In the present article, we feature a case-based scenario focusing on the role of the radiologist in this type of multidisciplinary team.
Abstract
Background
While it is clear that neuroendocrine tumours of the appendix (NET-A) <1 cm can be treated with a simple appendectomy alone, management of NET-A between 1- to 2 cm and > 2cm ...remains controversial. Current guidelines suggest that a right hemicolectomy (RHC) is recommended for tumours >2 cm and for tumours 1- to 2 cm with high risk features such as deep mesoappendiceal invasion (MAI), high Ki67 and/or high mitotic rate. The rates of lymph node (LN) metastasis in patients who had RHC for tumours >2 cm is variable in literature, ranging from 0–50%. Even in the cases of LN invasion, there is still unclear evidence to show that RHC improves overall survival or that it is clinically justified. Since there are no standardized adjuvant treatments for NET-A, the LN status would not further inform additional therapy, thus questioning its role in practice.
Aims
Given the indolent nature of these tumours, the notion of over-treatment with RHC in patients with NET-A between 1- to 2 cm and >2 cm arises. Theobjective of this study is to assess the role of RHC in the management of NET-A. This was achieved by determining the nodal positivity rate based on size and by examining the relationship between the surgical approach used, various prognostic factors (tumour location, MAI, LN invasion, etc.), post-operative complication rates, and survival outcomes.
Methods
An 8-year retrospective study was performed on patients with a pathological diagnosis of NET-A. Patients were excluded if they had a diagnosis of a non-appendiceal neuroendocrine tumour or an appendiceal non-neuroendocrine tumour.
Results
Forty-nine patients were identified with a diagnosis of a NET-A (mean age 40.4, 95% CI 36.3–44.5). Twenty-seven tumours (55%) were <1cm, eighteen (37%) were 1-2cm, and four (8%) were >2cm. Five patients with tumours <1cm had RHC (19%), while seven had one with tumours 1-2cm (39%). All four patients with tumours >2cm had RHC. Of the tumours <1cm, none were node-positive, while 11% of tumours 1-2cm were node-positive. All tumours >2cm had node-positive disease. The overall complication rate for patients who were treated with RHC was 31%. Based on the Clavien-Dindo classification, there were two grade I, one grade II, and two grade III complications. There was no recurrence of disease and there were no deaths due to NET-A across all patients.
Conclusions
The use of a right hemicolectomy is shown to be unnecessary for tumours <1cm. In tumours >2cm, all patients had nodal disease – while it may not affect overall survival, its use may be justified to reduce the risk of local disease recurrence. A minority of patients had positive nodal disease in the 1-2cm group. In these cases, the risks of surgery vs. observation should be balanced to prevent the risk of over-treatment, especially with the lack of evidence for the benefit to overall survival.
Funding Agencies
None
Background
Schwannomas are rare tumours that pose a significant management challenge in the abdomen, retroperitoneum and pelvis. No data are available to inform management strategy.
Methods
A ...collaborative international cohort study, across specialist sarcoma units, was conducted to include adults presenting between 2000 and 2017 with histopathologically confirmed schwannomas within the abdomen, retroperitoneum or pelvis.
Results
Of 485 patients across 12 centres, 38 (7·8 per cent) were discharged without follow‐up, 199 (41·0 per cent) underwent early resection and 248 (51·1 per cent) had radiological monitoring. Of these 248 patients, 96 (38·7 per cent) eventually had surgery, giving an overall resection rate of 60·8 per cent (295 of 485). At baseline, median tumour volume was 90·1 (i.q.r. 26·5–262·0) cm3. The estimated growth rate was 10·5 (95 per cent c.i. 9·4 to 11·6) per cent per year, and was consistent in the short term (within 2 years of diagnosis) and long term (beyond 2 years) (ρ = 0·405, P = 0·021). A decision to operate was more common in symptomatic patients (P < 0·001) and for rapidly growing tumours (growth rate more than 20 per cent per year) (P = 0·025). R0/R1 resection was achieved in 91·6 per cent of patients (263 of 287). Kaplan–Meier long‐term recurrence rates after R0/R1 resection were 2·3 and 6·7 per cent at 3 and 5 years respectively.
Conclusion
Specific recommendations include: indications for early surgery, prediction of growth from radiological monitoring, promotion of selective submacroscopic resection and cessation of postoperative imaging surveillance.
Antecedentes
Los schwannomas son tumores raros que plantean un importante desafío para su tratamiento en el abdomen, retroperitoneo y pelvis. No existen datos disponibles que informen de la estrategia de tratamiento.
Métodos
Se llevó a cabo un estudio de cohortes colaborativo internacional, entre unidades especializadas en sarcomas, que incluía a pacientes adultos con schwannomas de la cavidad abdominal, retroperitoneo o pelvis con confirmación histológica que se presentaron entre 2000 y 2017.
Resultados
De 485 pacientes de los 12 centros, 38 (7,8%) fueron dados de alta sin seguimiento, 199 (41,0%) fueron sometidos a resección precoz y 248 (51,1%) pacientes se incluyeron en seguimiento radiológico, de estos últimos 96 pacientes (38,7%) fueron sometidos finalmente a cirugía, con una tasa global de resección del 60,8% (295/485). Al inicio, la mediana del volumen tumoral fue 90,1 cm3 (rango intercuartílico: 26,5‐262,0). La tasa media de crecimiento fue 10,5% por año (i.c. del 95%: 9,4%‐11,6%), siendo uniforme en el seguimiento a corto (durante los 2 años del diagnóstico) y largo plazo (más allá de los 2 años, rho: 0,405, P = 0,021). La decisión de establecer la indicación quirúrgica fue más frecuente en pacientes sintomáticos (P < 0,001) y en tumores con crecimiento rápido (> 20% por año, P = 0,025). Se consiguió una resección R0/R1 en el 91,6%. Las tasas de recidiva a largo plazo de Kaplan‐Meier tras resección R0/R1 fueron 2% y 7% a 3 y 5 años, respectivamente.
Conclusión
Las recomendaciones específicas incluyen: indicaciones para la cirugía precoz, predicción del crecimiento en el seguimiento radiológico, fomentar la resección submacroscópica selectiva, y cese del seguimiento postoperatorio con pruebas de imagen.
Schwannomas present a significant management challenge, and surgery can result in morbidity. Individualized growth rates predicted after a period of radiological monitoring can help guide decision‐making. There is no role for surveillance after resection.
Practical guidelines
Triple negative breast cancer (TNBC) accounts for 15%–20% of all breast cancers but disproportionately accounts for the majority of breast cancer related deaths. Within TNBC, cancer stem cells (CSCs) ...exist in interconvertible mesenchymal or epithelial sup-populations that cannot be simultaneously targeted by non-specific chemotherapy highlighting the necessity of a therapeutic approach which targets both subpopulations. However, these CSC populations differ dramatically, making therapeutic approaches illusive.
Initially, we identified that Wnt and YAP signalling suppressed both mesenchymal and epithelial CSCs in vitro and in vivo using TNBC cell lines, patients’ tumour samples, and a database of 2509 patients with invasive breast cancer. Subsequently, we encapsulated Wnt and YAP inhibitors (PRI-724 and simvastatin respectively) in polyethylene glycol–polylactic acid nanoparticles (NPs) to increase intra-tumoral specificity and accumulation. Mice were implanted with patient derived xenografts (PDX) and were treated with NP-encapsulated PRI-724 and simvastatin. Additionally, NP accumulation within the tumour verses other organs was tracked using NP-conjugated fluorophores followed by flow cytometry and in vivo imaging system analysis (IVIS). To determine CSC and tumorigenesis, secondary transplantation was performed after NP treatment.
NP-encapsulated PRI-724 and simvastatin effectively suppressed Wnt and YAP gene expression in vitro. NP-encapsulated inhibitors were tolerable in vivo and accumulated in the TNBC PDX tumours. In contrast to paclitaxel (a commonly employed chemotherapeutic agent), NP-encapsulated PRI-724 and simvastatin markedly reduced the epithelial (ALDH+) and mesenchymal (CD44+/CD24-) CSC subpopulations. Additionally, co-administration of NP-encapsulated inhibitors with paclitaxel potently retarded the growth of TNBC PDX tumours but significantly maintained diminished epithelial (ALDH+) and mesenchymal (CD44+/CD24-) CSC populations.
We developed a novel, tangible approach for the treatment of TNBC using NP-encapsulated Wnt and YAP inhibitors which accumulated in TNBC PDX tumours and potently retarded tumour growth, and inhibited CSC enrichment and tumorigenicity.
Comment expliquer que, malgré une loi du 31 décembre 1970 interdisant l’usage et le trafic de cannabis, la consommation de cette substance n’a fait qu’augmenter durant les trente années suivantes, ...aboutissant au début des années 2000 à un million et demi d’usagers réguliers en France ? C’est à cette question que tente de répondre Erwan Pointeau-Lagadec dans l’ouvrage issu de sa thèse de doctorat, soutenue en 2019, pour lequel il a été lauréat du prix scientifique de L’Harmattan en 2021. L’ar...
Dense millimeter-tall carpets of vertically aligned carbon nanotubes (VACNTs) were grown using thermal chemical vapor deposition (CVD) from ethylene and hydrogen gases with two or three independently ...controlled hot zones while introducing controlled flows of oxygen. Through preheating, oxygen and hydrogen reacted through a multi-step reaction to form water, enabling the growth of tall CNT carpets. This process showed a large tolerance for variations of O2, H2, and C2H4. The measured water vapor produced was half the theoretical maximum. The residence time strongly affected the decomposition of the gases. The simplicity and robustness of this CVD process provides a simpler alternative to direct addition of water vapor for manufacturing tall carpets of aligned CNTs with a high level of control.
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