Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL

Unilateral inguinofemoral lymphadenectomy in patients with early-stage vulvar squamous cell carcinoma and a unilateral metastatic sentinel lymph node is safe.

OBJECTIVE: Optimal management of the contralateral groin in patients with early-stage vulvar squamous cell carcinoma (VSCC) and a metastatic unilateral inguinal sentinel lymph node (SN) is unclear. We analyzed patients who participated in GROINSS-V I or II to determine whether treatment of the contralateral groin can safely be omitted in patients with a unilateral metastatic SN. METHODS: We selected the patients with a unilateral metastatic SN from the GROINSS-V I and II databases. We determined the incidence of contralateral additional non-SN metastases in patients with unilateral SN-metastasis who underwent bilateral inguinofemoral lymphadenectomy (IFL). In those who underwent only ipsilateral groin treatment or no further treatment, we determined the incidence of contralateral groin recurrences during follow-up. RESULTS: Of 1912 patients with early-stage VSCC, 366 had a unilateral metastatic SN. Subsequently, 244 had an IFL or no treatment of the contralateral groin. In seven patients (7/244; 2.9% [95% CI: 1.4%-5.8%]) disease was diagnosed in the contralateral groin: five had contralateral non-SN metastasis at IFL and two developed an isolated contralateral groin recurrence after no further treatment. Five of them had a primary tumor ≥30 mm. Bilateral radiotherapy was administered in 122 patients, of whom one (1/122; 0.8% [95% CI: 0.1%-4.5%]) had a contralateral groin recurrence. CONCLUSION: The risk of contralateral lymph node metastases in patients with early-stage VSCC and a unilateral metastatic SN is low. It appears safe to limit groin treatment to unilateral IFL or inguinofemoral radiotherapy in these cases

The changing form of Antarctic biodiversity

Antarctic biodiversity is much more extensive, ecologically diverse and biogeographically structured than previously thought. Understanding of how this diversity is distributed in marine and terrestrial systems, the mechanisms underlying its spatial variation, and the significance of the microbiota is growing rapidly. Broadly recognizable drivers of diversity variation include energy availability and historical refugia. The impacts of local human activities and global environmental change nonetheless pose challenges to the current and future understanding of Antarctic biodiversity. Life in the Antarctic and the Southern Ocean is surprisingly rich, and as much at risk from environmental change as it is elsewher

α2,3-Sialyltransferase ST3Gal III Modulates Pancreatic Cancer Cell Motility and Adhesion In Vitro and Enhances Its Metastatic Potential In Vivo

Background: Cell surface sialylation is emerging as an important feature of cancer cell metastasis. Sialyltransferase expression has been reported to be altered in tumours and may account for the formation of sialylated tumour antigens. We have focused on the influence of alpha-2,3-sialyltransferase ST3Gal III in key steps of the pancreatic tumorigenic process. Methodology/Principal Findings: ST3Gal III overexpressing pancreatic adenocarcinoma cell lines Capan-1 and MDAPanc-28 were generated. They showed an increase of the tumour associated antigen sialyl-Lewis x. The transfectants ’ E-selectin binding capacity was proportional to cell surface sialyl-Lewis x levels. Cellular migration positively correlated with ST3Gal III and sialyl-Lewis x levels. Moreover, intrasplenic injection of the ST3Gal III transfected cells into athymic nude mice showed a decrease in survival and higher metastasis formation when compared to the mock cells. Conclusion: In summary, the overexpression of ST3Gal III in these pancreatic adenocarcinoma cell lines underlines the rol

Sentinel node dissection is safe in the treatment of early-stage vulvar cancer

Purpose To investigate the safety and clinical utility of the sentinel node procedure in early-stage vulvar cancer patients. Patients and Methods A multicenter observational study on sentinel node detection using radioactive tracer and blue dye was performed in patients with T1/2 (<4 cm) squamous cell cancer of the vulva. When the sentinel node was found to be negative at pathologic ultrastaging, inguinofemoral lymphadenectomy was omitted, and the patient was observed with follow-up for 2 years at intervals of every 2 months. Stopping rules were defined for the occurrence of groin recurrences. Results From March 2000 until June 2006, a sentinel node procedure was performed in 623 groins of 403 assessable patients. In 259 patients with unifocal vulvar disease and a negative sentinel node (median follow-up time, 35 months), six groin recurrences were diagnosed (2.3%; 95% CI, 0.6% to 5%), and 3-year survival rate was 97% (95% CI, 91% to 99%). Short-term morbidity was decreased in patients after sentinel node dissection only when compared with patients with a positive sentinel node who underwent inguinofemoral lymphadenectomy (wound breakdown in groin: 11.7% v 34.0%, respectively; P<.0001; and cellulitis: 4.5% v 21.3%, respectively; P<.0001). Long-term morbidity also was less frequently observed after removal of only the sentinel node compared with sentinel node removal and inguinofemoral lymphadenectomy (recurrent erysipelas: 0.4% v 16.2%, respectively; P<.0001; and lymphedema of the legs: 1.9% v 25.2%, respectively; P<.0001). Conclusion In early-stage vulvar cancer patients with a negative sentinel node, the groin recurrence rate is low, survival is excellent, and treatment-related morbidity is minimal. We suggest that sentinel node dissection, performed by a quality-controlled multidisciplinary team, should be part of the standard treatment in selected patients with early-stage vulvar cancer

Sentinel nodes in vulvar cancer: Long-term follow-up of the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V) I

OBJECTIVE: In 2008 GROINSS-V-I, the largest validation trial on the sentinel node (SN) procedure in vulvar cancer, showed that application of the SN-procedure in patients with early-stage vulvar cancer is safe. The current study aimed to evaluate long-term follow-up of these patients regarding recurrences and survival. METHODS: From 2000 until 2006 GROINSS-V-I included 377 patients with unifocal squamous cell carcinoma of the vulva (T1, <4 cm), who underwent the SN-procedure. Only in case of SN metastases an inguinofemoral lymphadenectomy was performed. For the present study follow-up was completed until March 2015. RESULTS: Themedian follow-up was 105 months (range 0–179). The overall local recurrence ratewas 27.2% at 5 years and 39.5% at 10 years after primary treatment, while for SN-negative patients 24.6% and 36.4%, and for SN-positive patients 33.2% and 46.4% respectively (p = 0.03). In 39/253 SN-negative patients (15.4%) an inguinofemoral lymphadenectomy was performed, because of a local recurrence. Isolated groin recurrence rate was 2.5% for SN-negative patients and 8.0% for SN-positive patients at 5 years. Disease-specific 10-year survival was 91% for SN-negative patients compared to 65% for SN-positive patients (p b .0001). For all patients, 10-year disease-specific survival decreased from 90% for patients without to 69% for patients with a local recurrence (p b .0001).publisher: Elsevier articletitle: Sentinel nodes in vulvar cancer: Long-term follow-up of the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V) I journaltitle: Gynecologic Oncology articlelink: http://dx.doi.org/10.1016/j.ygyno.2015.09.077 content_type: article copyright: Copyright © 2015 Elsevier Inc. All rights reserved.status: publishe

Atmospheric trace gases support primary production in Antarctic desert surface soil

Cultivation-independent surveys have shown that the desert soils of Antarctica harbour surprisingly rich microbial communities. Given that phototroph abundance varies across these Antarctic soils, an enduring question is what supports life in those communities with low photosynthetic capacity. Here we provide evidence that atmospheric trace gases are the primary energy sources of two Antarctic surface soil communities. We reconstructed 23 draft genomes from metagenomic reads, including genomes from the candidate bacterial phyla WPS-2 and AD3. The dominant community members encoded and expressed high-affinity hydrogenases, carbon monoxide dehydrogenases, and a RuBisCO lineage known to support chemosynthetic carbon fixation. Soil microcosms aerobically scavenged atmospheric H2 and CO at rates sufficient to sustain their theoretical maintenance energy and mediated substantial levels of chemosynthetic but not photosynthetic CO2 fixation. We propose that atmospheric H2, CO2 and CO provide dependable sources of energy and carbon to support these communities, which suggests that atmospheric energy sources can provide an alternative basis for ecosystem function to solar or geological energy sources. Although more extensive sampling is required to verify whether this process is widespread in terrestrial Antarctica and other oligotrophic habitats, our results provide new understanding of the minimal nutritional requirements for life and open the possibility that atmospheric gases support life on other planets