Management of non-visualization following dynamic sentinel lymph node biopsy for squamous cell carcinoma of the penis

Objectives: To review the management and clinical outcomes of uni- or bilateral non-visualization of inguinal lymph nodes during dynamic sentinel lymph node biopsy (DSNB) in patients diagnosed with penile cancer and clinically impalpable inguinal lymph nodes (cN0), and to develop an algorithm for the management of patients in which non-visualization occurs. Patients and Methods: This is a retrospective observational study over a period of 4 years, comprising 166 patients with penile squamous cell carcinoma undergoing DSNB and followed up for a minimum of 6 months. All cases diagnosed with uni- or bilateral non-visualization of sentinel nodes in this cohort were identified from a penile cancer database. The management of the inguinal lymph nodes after non-visualization and the oncological outcomes including local and regional recurrence rates were documented. Results: Out of 166 consecutive patients undergoing DSNB, 20 patients (12%) had unilateral non-visualization after injection of intradermal 99mTc. Of these 20 patients, seven underwent repeat DSNB at a later date, with six having successful visualization. One patient had persistent non-visualization and proceeded to a superficial modified inguinal lymphadenectomy (SML). None of these patients experienced recurrence at follow-up. A further seven patients underwent modified SML with on-table frozen-section analysis of the lymph node packet; none of these patients were found to have micrometastatic disease in the inguinal lymph nodes, although one patient developed metastatic inguinal node disease at a later date. Six patients elected to undergo clinical surveillance and have remained disease-free. Conclusion: Patients with impalpable inguinal lymph nodes undergoing DSNB with ≥G2 T1 disease should ideally have bilateral visualization of the sentinel lymph nodes, reflecting the drainage pattern from the primary tumour. In the present series, 12% of patients were found to have unilateral non-visualization after DSNB. Among patients offered a repeat DSNB at a later date, localizing the sentinel node was successful in 86% of cases. Patients with favourable histological characteristics can be placed on clinical surveillance. Those with high-risk disease can be offered a repeat DSNB procedure on the proviso that SML may be carried out if there is repeated non-visualization. Larger cohorts are required to validate this proposed algorithm

Integration of D-dimensional 2-factor spaces cosmological models by reducing to the generalized Emden-Fowler equation

The D-dimensional cosmological model on the manifold $M = R \times M_{1} \times M_{2}$ describing the evolution of 2 Einsteinian factor spaces, $M_1$ and $M_2$, in the presence of multicomponent perfect fluid source is considered. The barotropic equation of state for mass-energy densities and the pressures of the components is assumed in each space. When the number of the non Ricci-flat factor spaces and the number of the perfect fluid components are both equal to 2, the Einstein equations for the model are reduced to the generalized Emden-Fowler (second-order ordinary differential) equation, which has been recently investigated by Zaitsev and Polyanin within discrete-group analysis. Using the integrable classes of this equation one generates the integrable cosmological models. The corresponding metrics are presented. The method is demonstrated for the special model with Ricci-flat spaces $M_1,M_2$ and the 2-component perfect fluid source.Comment: LaTeX file, no figure

Toda chains with type A_m Lie algebra for multidimensional m-component perfect fluid cosmology

We consider a D-dimensional cosmological model describing an evolution of Ricci-flat factor spaces, M_1,...M_n (n > 2), in the presence of an m-component perfect fluid source (n > m > 1). We find characteristic vectors, related to the matter constants in the barotropic equations of state for fluid components of all factor spaces. We show that, in the case where we can interpret these vectors as the root vectors of a Lie algebra of Cartan type A_m=sl(m+1,C), the model reduces to the classical open m-body Toda chain. Using an elegant technique by Anderson (J. Math. Phys. 37 (1996) 1349) for solving this system, we integrate the Einstein equations for the model and present the metric in a Kasner-like form.Comment: LaTeX, 2 ps figure

GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1.

Summary: A male patient with a germline mutation in MEN1 presented at the age of 18 with classical features of gigantism. Previously, he had undergone resection of an insulin-secreting pancreatic neuroendocrine tumour (pNET) at the age of 10 years and had subtotal parathyroidectomy due to primary hyperparathyroidism at the age of 15 years. He was found to have significantly elevated serum IGF-1, GH, GHRH and calcitonin levels. Pituitary MRI showed an overall bulky gland with a 3 mm hypoechoic area. Abdominal MRI showed a 27 mm mass in the head of the pancreas and a 6 mm lesion in the tail. Lanreotide-Autogel 120 mg/month reduced GHRH by 45% and IGF-1 by 20%. Following pancreaticoduodenectomy, four NETs were identified with positive GHRH and calcitonin staining and Ki-67 index of 2% in the largest lesion. The pancreas tail lesion was not removed. Post-operatively, GHRH and calcitonin levels were undetectable, IGF-1 levels normalised and GH suppressed normally on glucose challenge. Post-operative fasting glucose and HbA1c levels have remained normal at the last check-up. While adolescent-onset cases of GHRH-secreting pNETs have been described, to the best of our knowledge, this is the first reported case of ectopic GHRH in a paediatric setting leading to gigantism in a patient with MEN1. Our case highlights the importance of distinguishing between pituitary and ectopic causes of gigantism, especially in the setting of MEN1, where paediatric somatotroph adenomas causing gigantism are extremely rare. Learning points: It is important to diagnose gigantism and its underlying cause (pituitary vs ectopic) early in order to prevent further growth and avoid unnecessary pituitary surgery. The most common primary tumour sites in ectopic acromegaly include the lung (53%) and the pancreas (34%) (1): 76% of patients with a pNET secreting GHRH showed a MEN1 mutation (1). Plasma GHRH testing is readily available in international laboratories and can be a useful diagnostic tool in distinguishing between pituitary acromegaly mediated by GH and ectopic acromegaly mediated by GHRH. Positive GHRH immunostaining in the NET tissue confirms the diagnosis. Distinguishing between pituitary (somatotroph) hyperplasia secondary to ectopic GHRH and pituitary adenoma is difficult and requires specialist neuroradiology input and consideration, especially in the MEN1 setting. It is important to note that the vast majority of GHRH-secreting tumours (lung, pancreas, phaeochromocytoma) are expected to be visible on cross-sectional imaging (median diameter 55 mm) (1). Therefore, we suggest that a chest X-ray and an abdominal ultrasound checking the adrenal glands and the pancreas should be included in the routine work-up of newly diagnosed acromegaly patients

Fast Algorithms For Josephson Junction Arrays : Bus--bars and Defects

We critically review the fast algorithms for the numerical study of two--dimensional Josephson junction arrays and develop the analogy of such systems with electrostatics. We extend these procedures to arrays with bus--bars and defects in the form of missing bonds. The role of boundaries and of the guage choice in determing the Green's function of the system is clarified. The extension of the Green's function approach to other situations is also discussed.Comment: Uuencoded 1 Revtex file (11 Pages), 3 Figures : Postscript Uuencode

Dilaton Contributions to the Cosmic Gravitational Wave Background

We consider the cosmological amplification of a metric perturbation propagating in a higher-dimensional Brans-Dicke background, including a non trivial dilaton evolution. We discuss the properties of the spectral energy density of the produced gravitons (as well as of the associated squeezing parameter), and we show that the present observational bounds on the graviton spectrum provide significant information on the dynamical evolution of the early universe.Comment: 26 pages, plain tex (to appear in Phys.Rev.D, 1 fig available from the authors upon req.

Antibacterial, Remineralising and Matrix Metalloproteinase Inhibiting Scandium-doped Phosphate Glasses for Treatment of Dental Caries

Objectives: Antibiotic resistance is increasingly a growing global threat. This study aimed to investigate the potential use of newly developed scandium-doped phosphate-based glasses (Sc-PBGs) as an antibacterial and anticariogenic agent through controlled release of Sc3+ ions. Methods: Sc-PBGs with various calcium and sodium oxide contents were produced and characterised using thermal and spectroscopic analysis. Degradation behaviour, ion release, antibacterial action against Streptococcus mutans, anti-matrix metalloproteinase-2 (MMP-2) activity, remineralisation potential and in vivo biocompatibility were also investigated. Results: The developed glass system showed linear Sc3+ ions release over time. The released Sc3+ shows statistically significant inhibition of S. mutans biofilm (1.2 log10 CFU reduction at 6 h) and matrix metalloproteinase-2 (MMP-2) activity, compared with Sc-free glass and positive control. When Sc-PBGs were mounted alongside enamel sections, subjected to acidic challenges, alternating hyper- and hypomineralisation layers consistent with periods of re- and demineralisation were observed demonstrating their potential remineralising action. Furthermore, Sc-PBGs produced a non-toxic response when implanted subcutaneously for 2 weeks in Sprague Dawley rats. Significance: Since Sc3+ ions might act on various enzymes essential to the biological mechanisms underlying caries, Sc-PBGs could be a promising therapeutic agent against cariogenic bacteria

Metric Perturbations in Dilaton-Driven Inflation

We compute the spectrum of scalar and tensor metric perturbations generated, as amplified vacuum fluctuations, during an epoch of dilaton-driven inflation of the type occurring naturally in string cosmology. In the tensor case the computation is straightforward while, in the scalar case, it is made delicate by the appearance of a growing mode in the familiar longitudinal gauge. In spite of this, a reliable perturbative calculation of perturbations far outside the horizon can be performed by resorting either to appropriate gauge invariant variables, or to a new coordinate system in which the growing mode can be "gauged down". The simple outcome of this complicated analysis is that both scalar and tensor perturbations exhibit nearly Planckian spectra, whose common "temperature" is related to some very basic parameters of the string-cosmology background.Comment: 34 pages, latex, no figure

Scalar and Tensor Inhomogeneities from Dimensional Decoupling

We discuss some perturbative techniques suitable for the gauge-invariant treatment of the scalar and tensor inhomogeneities of an anisotropic and homogeneous background geometry whose spatial section naturally decomposes into the direct product of two maximally symmetric Eucledian manifolds, describing a general situation of dimensional decoupling in which $d$ external dimensions evolve (in conformal time) with scale factor $a(\eta)$ and $n$ internal dimensions evolve with scale factor $b(\eta)$. We analyze the growing mode problem which typically arises in contracting backgrounds and we focus our attention on the situation where the amplitude of the fluctuations not only depends on the external space-time but also on the internal spatial coordinates. In order to illustrate the possible relevance of this analysis we compute the gravity waves spectrum produced in some highly simplified model of cosmological evolution and we find that the spectral amplitude, whose magnitude can be constrained by the usual bounds applied to the stochastic gravity waves backgrounds, depends on the curvature scale at which the compactification occurs and also on the typical frequency of the internal excitations.Comment: 31 pages, Latex, DAMTP 96-92, UCM 96-04, to appear in Phys. Rev. D 55 (1997