Resection of sentinel lymph nodes by an extraperitoneal minilaparoscopic approach using indocyanine green for uterine malignancies: a preclinical comparative study

Background. The sentinel lymph node (SLN) concept might minimize surgical aggressiveness in cervical and endometrial malignancies. The aim of the study was to test the feasibility and reliability of minilaparoscopic extraperitoneal SLN excision after indocyanine green (ICG) cervical injection using a high-definition near infrared (NIR) imaging system in an in vivo porcine model. The same procedure was performed using conventional laparoscopic instruments and both outcomes were compared. Methods. Twenty-four animals were equally and randomly divided into a minilaparoscopic group (group A) and a 5-mm conventional laparoscopic group (group B). A high-definition NIR imaging system and a 30 degrees ICG endoscope were used. First, ICG (0.5 mL) was injected in the paracervical region. The SLN coloring time was recorded. An extraperitoneal approach to the SLN was executed with the same CO2 retropneumoperitoneum pressures (10 mm Hg). In both groups, the times for SLN localization and excision, as well as complications, were registered. Finally, a laparotomy was then done to evaluate whether any stained SLN still remained. The same surgical team performed all experiments. Results. SLNs were identified and extraperitoneally excised in all animals without major complications. The SLN localization varied between animals from external iliac to preaortic regions. The surgical times were shorter with minilaparoscopy (39.3 +/- 13 minutes) than with conventional 5-mm instruments (51.3 +/- 14.17 minutes; P = .042). In group B, one stained SLN remained and was only detected by laparotomy. Conclusions. We confirmed the feasibility and reliability of extraperitoneal minilaparoscopic approach for identification, dissection, and excision of SLN using an NIR imaging system and ICG.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Science & Technology Foundation (FCT), Portugal—PTDC/SAU-OSM/105578/2008.info:eu-repo/semantics/publishedVersio

Thick primary melanoma has a heterogeneous tumor biology: an institutional series

<p>Abstract</p> <p>Background</p> <p>Thick melanomas (TM) ≥4 mm have a high risk for nodal and distant metastases. Optimal surgical management, prognostic significance of sentinel node biopsy (SLNB), and benefits of interferon (IFN) for these patients are unclear. As a continuum of increasing tumor thickness is placed into a single TM group, differences in biologic and clinical behavior may be lost. The purpose of this study was to better characterize the diverse biology in TM, including the value of increasing thickness and nodal status information, potentially identifying high risk TM subgroups that may warrant more aggressive treatment/follow up.</p> <p>Methods</p> <p>155 consecutive TM patients treated at a single institution between 1971 and 2007 were retrospectively reviewed. Patient, disease and treatment features were analyzed with respect to disease-free (DFS) and overall survival (OS).</p> <p>Results</p> <p>Median patient age was 66 years and 68% of patients were men. The trunk was the most common TM location (35%), followed by the head and neck (29%) and lower extremities (20%). Median thickness was 6 mm and 61% were ulcerated. 6% patients had stage IV disease, 12% had clinical nodal metastases. Clinically negative lymph node basins were treated by observation (22 patients - 15.4%), elective lymph node dissection (ELND) (24 patients - 17.6%) or SLNB (91 patients - 67%). 75% of ELND's and 53% of SLNB's were positive. Completion node dissection was performed in 38 SLNB+ patients and 22% had additional positive nodes. 17% of the study patients received IFN. At median follow up of 26 months, 5 year DFS and OS were 42% and 43.6%. For SLNB positive vs negative, median DFS were 22 vs 111 months (p = 0.006) and median OS were 41 vs 111 months (p = 0.006). When stratified by tumor thickness ≤ vs > 6 mm, 5 year DFS was 58.3% vs 20% (p < 0.0001) and OS was 62% vs 20% (P < 0.0001). IFN had no impact on DFS or OS (p = 0.98 and 0.8 respectively).</p> <p>Conclusion</p> <p>Within the high risk group of patients with TM, cases with tumor thickness > 6 mm or a positive SLNB had a significantly worse DFS and OS (p < .0001, <.0001 and .006, .006).</p

Adjuvant radiation therapy in metastatic lymph nodes from melanoma

<p>Abstract</p> <p>Purpose</p> <p>To analyze the outcome after adjuvant radiation therapy with standard fractionation regimen in metastatic lymph nodes (LN) from cutaneous melanoma.</p> <p>Patients and methods</p> <p>86 successive patients (57 men) were treated for locally advanced melanoma in our institution. 60 patients (69%) underwent LN dissection followed by radiation therapy (RT), while 26 patients (31%) had no radiotherapy.</p> <p>Results</p> <p>The median number of resected LN was 12 (1 to 36) with 2 metastases (1 to 28). Median survival after the first relapse was 31.8 months. Extracapsular extension was a significant prognostic factor for regional control (p = 0.019). Median total dose was 50 Gy (30 to 70 Gy). A standard fractionation regimen was used (2 Gy/fraction). Median number of fractions was 25 (10 to 44 fractions). Patients were treated with five fractions/week. Patients with extracapsular extension treated with surgery followed by RT (total dose ≥50 Gy) had a better regional control than patients treated by surgery followed by RT with a total dose <50 Gy (80% vs. 35% at 5-year follow-up; p = 0.004).</p> <p>Conclusion</p> <p>Adjuvant radiotherapy was able to increase regional control in targeted sub-population (LN with extracapsular extension).</p

Therapeutic Surgical Management of Palpable Melanoma Groin Metastases: Superficial or Combined Superficial and Deep Groin Lymph Node Dissection

Item does not contain fulltextBACKGROUND: Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or combined superficial and deep groin dissection (CGD) according to most literature, but in practice superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate the experience in CGD versus SGD patients in our center. METHODS: Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months. RESULTS: In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no involved deep lymph nodes (p = 0.001). Preoperative computed tomography (CT) scan had high negative predictive value of 91% for detection of pelvic nodal involvement. CONCLUSIONS: This study demonstrated that survival and local control do not differ for patients with palpable groin metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep nodes on CT scan

Adenocarcinoma arising in a cystic duplication of the small bowel: case report and review of literature

Enteric duplications are rare, but can occur anywhere along the digestive tract. Most of the patients become symptomatic in early childhood and only a few cases of adult patients have been reported in literature. Here we report a unique case of an adenocarcinoma arising in a coincidentally found cystic duplication of the small bowel

Matrix Metalloproteinase-9 (MMP-9) polymorphisms in patients with cutaneous malignant melanoma

BACKGROUND: Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs) play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk. METHODS: We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis. RESULTS: We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site. CONCLUSION: This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression

Spotlight on landmark oncology trials: the latest evidence and novel trial designs

The era of precision oncology is marked with prominent successes in the therapy of advanced soft tissue sarcomas, breast cancer, ovarian cancer and haematological neoplasms, among others. Moreover, recent trials of immune checkpoint inhibitors in melanoma, non-small cell lung carcinoma, and head and neck cancers have significantly influenced the therapeutic landscape by providing promising evidence for immunotherapy efficacy in the adjuvant setting in high-risk locoregional disease. To speed up the introduction of targeted therapy for cancer patients, novel phase II trials are being designed, and may likely form the basis for the 'landmark trials' of the future. A special article collection in BMC Medicine, "Spotlight on landmark oncology trials", features articles from invited experts on recent clinical practice-changing trials

Targeted agents and immunotherapies: optimizing outcomes in melanoma

Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents. During this period, the treatment paradigm for BRAF-mutant disease has evolved rapidly: the standard-of-care BRAF-targeted approach has shifted from single-agent BRAF inhibition to combination therapy with a BRAF and a MEK inhibitor. Concurrently, immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and, now, the programmed cell-death protein 1 (PD-1) immune checkpoints. These changes in the treatment landscape have dramatically improved patient outcomes, with the median overall survival of patients with advanced-stage melanoma increasing from approximately 9 months before 2011 to at least 2 years - and probably longer for those with BRAF-V600-mutant disease. Herein, we review the clinical trial data that established the standard-of-care treatment approaches for advanced-stage melanoma. Mechanisms of resistance and biomarkers of response to BRAF-targeted treatments and immunotherapies are discussed, and the contrasting clinical benefits and limitations of these therapies are explored. We summarize the state of the field and outline a rational approach to frontline-treatment selection for each individual patient with BRAF-mutant melanoma