Sentinel lymph node biopsy based on anatomical landmarks and locoregional mapping of inguinofemoral sentinel lymph nodes in women with vulval cancer: an operative technique.

Inguinal lymph node involvement is the most robust predictor of mortality in vulval cancer and sentinel lymph node (SLN) biopsy is a safe diagnostic modality. We describe a technique based on anatomical landmarks. Our aims are (1) to describe the territorial mapping of SLNs, (2) to evaluate the associated complication rate vis-à-vis those reported in the literature, and (3) to assess its accuracy in detecting SLNs. Data from women who underwent groin SLN biopsies for vulval cancer at a single cancer centre were prospectively collected. All subjects met the GROINSS-V eligibility criteria. The location of the SLN relative to the saphenous vein was recorded. All women were followed up and early and late complications were recorded. The recurrence rate at the time of the census was calculated. A total of 71 groins in 44 women were included. The SLN was primarily located over Cloquet's node (85.2%). The incidence of early wound cellulitis and dehiscence were 2.8% and 11.3% while lymphocysts were present in 11.3% of groins. The negative nodal recurrence rate was 1.7%. Results showed that this reproducible technique allows access to 96.7% of SLNs, including both deep and superficial SLNs whilst minimising the need for extensive dissection and complications associated with overharvesting of lymph nodes.

What is already known on this subject? Inguinal sentinel lymph node (SLN) biopsy in women with vulval cancer is often construed as a challenging skill to master and the success rate of SLN detection is dependent on the experience and skill of the surgeon. A review of the literature has revealed that whilst studies have largely concentrated on the efficacy of different intraoperative detection modalities or histopathological protocols, the literature describing a standardised surgical technique remains deficient.What do the results of this study add? Our technique offers multiple advantages: our incision, albeit small, allows the operator to gain access to 96.7% of inguinal SLNs and facilitates access to both deep and superficial SLNs regardless of patients' body mass index, minimises the need for extensive dissection and hence reduces the incidence of complications associated with overharvesting of lymph nodes such as lymphoedema or lymphocysts, particularly in obese women. Our local figures also support the safety of this operative technique (negative nodal recurrence rate 1.7%) and compare favourably with those from the GROINSS-V study.What are the implications of these findings for clinical practice and/or further research? We describe a reproducible technique based on anatomical landmarks and an appreciation of the territorial mapping of inguinal SLN to optimise the chances of identifying the inguinal SLN in women with vulval cancer while circumventing the sequelae often attributed to this procedure.

The role of preoperative computerized tomography (CT) scan of the pelvis and groin in the management of clinically early staged vulva squamous cell carcinoma.

INTRODUCTION: Vulvar squamous cell carcinoma (VSCC) commonly metastasises through groin lymphatics. However, the use of pre-operative imaging in detecting inguinal nodal metastasis before staging surgery or to triage patients for sentinel node biopsy remains unclear. Here, we investigated if pre-operative CT scan, the imaging choice in our cancer centre, influences the overall course of VSCC management in those patients without clinical evidence of groin lymphadenopathy. METHOD: The study comprised of a prospective cohort of 225 patients with VSCC who underwent staging surgery within a regional tertiary gynaecological cancer centre. Comprehensive information of the cohort's demography, clinicopathological variables and outcome data were collected and analysed. Findings of pre-operative imaging were compared with histological findings of inguinal lymph nodes following groin lymphadenectomy. Statistical analyses were performed using SPSS V24. RESULTS: Pre-operative CT scan was performed on 116 (56.6%) patients. The sensitivity and specificity of cross-sectional imaging in detecting groin lymphatic metastasis were 59.1% and 77.8%, respectively; while the positive (PPV) and negative predictive value (NPV) were 61.9% and 75.7%, respectively. In patients who had sentinel inguinal nodes biopsy, the sensitivity, specificity, PPV and NPV of CT scan in detecting inguinal node metastasis were 30.0%, 85.7%, 33.3% and 83.7%, respectively. There was no difference in disease-free and overall survival in those who received pre-operative imaging when compared to those who did not. CONCLUSION: Pre-operative CT scan may be omitted in early stage VSCC prior to surgical staging as it does not affect overall management and surgical outcomes.

CB1 receptor mediates the effects of glucocorticoids on AMPK activity in the hypothalamus.

AMP-activated protein kinase (AMPK), a regulator of cellular and systemic energy homeostasis, can be influenced by several hormones. Tissue-specific alteration of AMPK activity by glucocorticoids may explain the increase in appetite, the accumulation of lipids in adipose tissues, and the detrimental cardiac effects of Cushing's syndrome. Endocannabinoids are known to mediate the effects of various hormones and to influence AMPK activity. Cannabinoids have central orexigenic and direct peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). In our preliminary experiments, WT mice received implants of a corticosterone-containing pellet to establish a mouse model of Cushing's syndrome. Subsequently, WT and Cb1 (Cnr1)-knockout (CB1-KO) littermates were treated with corticosterone and AMPK activity in the hypothalamus, various adipose tissues, liver and cardiac tissue was measured. Corticosterone-treated CB1-KO mice showed a lack of weight gain and of increase in hypothalamic and hepatic AMPK activity. In adipose tissues, baseline AMPK activity was higher in CB1-KO mice, but a glucocorticoid-induced drop was observed, similar to that observed in WT mice. Cardiac AMPK levels were reduced in CB1-KO mice, but while WT mice showed significantly reduced AMPK activity following glucocorticoid treatment, CB1-KO mice showed a paradoxical increase. Our findings indicate the importance of the CB1 receptor in the central orexigenic effect of glucocorticoid-induced activation of hypothalamic AMPK activity. In the periphery adipose tissues, changes may occur independently of the CB1 receptor, but the receptor appears to alter the responsiveness of the liver and myocardial tissues to glucocorticoids. In conclusion, our data suggest that an intact cannabinoid pathway is required for the full metabolic effects of chronic glucocorticoid excess.

WITHDRAWN: Ghrelin in obesity and endocrine diseases.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, doi:10.1016/j.mce.2011.02.011. The duplicate article has therefore been withdrawn.

Ghrelin in obesity and endocrine diseases.

Ghrelin shows orexigenic effect through its action on the hypothalamic appetite-regulating pathways, while in the periphery ghrelin increases adipose tissue accumulation and has a diabetogenic effect on the liver and pancreas. Adenosine monophosphate-activated protein kinase (AMPK) has been suggested as one of the mediators of ghrelin's effects. Plasma ghrelin levels are dependent on body mass index as well as food intake patterns. Ghrelin levels are in general reduced in obese individuals and in subjects with insulin resistance. In contrast to other forms of obesity, patients with Prader-Willi syndrome (PWS) display high levels of ghrelin, reduced visceral adiposity and relative hypoinsulinemia. Relationships between obesity and common genomic variants of GHRL and GHS-R genes have been studied. Ghrelin may have a role in the weight-reducing effect of bariatric surgery; however, this is a much debated issue. Altered ghrelin levels have also been observed in Cushing's syndrome and thyroid disease probably due to the secondary insulin resistance in these subjects.