Primary Bartholin gland carcinoma: a report of seven cases

This study reviews our experience with 7 patients with primary Bartholin gland cancer (BGC) treated at the Queensland Gynaecological Cancer Centre (QCGC) and compares this with previously published data. A retrospective clinicopathologic review of all patients with primary BGC treated at QCGC from 1988 to 2000 was performed. Of the 7 patients treated, all underwent primary surgery and 5 of the 7 patients received radiotherapy postoperatively. All patients presented with a local swelling or a lump. Two had associated discharge and 2 had associated pain. Of the 7 patients, 2, 3 and 2 respectively were classified as having Stage IB, II or III disease. Five of the 7 patients had squamous cell carcinoma (SCC), one had adenoid-cystic carcinoma and 1 had a small-cell neuroendocrine cancer of the Bartholin gland. None of the patients with SCC developed recurrent disease. The patient with adenoid-cystic carcinoma experienced local recurrences at 4 years and again at 5 years and 3 months. Nine years after primary treatment she was diagnosed with pulmonary metastases. The patient with small-cell neuroendocrine cancer of the Bartholin gland was considered tumour-free after operation. Thorough imaging, including a CT scan of her chest, abdomen and pelvis showed no evidence of disease. She died 1 year and three months after diagnosis from disseminated pulmonary disease. We present the first report, of small cell neuroendocrine cancer of the Bartholin gland. Therapeutic principles in the management of vulval cancer at other sites appear to be appropriate for management of BGC.

Canine intra-nasal squamous cell carcinoma treated with chemotherapy prior to surgical resection

A 12-year-old male castrated Samoyed dog was presented with left-sided epistaxis and sneezing. Diagnostic procedures included haematology and biochemistry testing, thoracic radiography, fine needle aspiration of regional lymph nodes, CT, rhinoscopy, incisional biopsy and histopathology. Squamous cell carcinoma of the rostral nasal cavity was diagnosed, with no evidence of metastatic disease. External beam radiation was not an accessible treatment option. Complete surgical resection of the tumour would have required a larger, more disfiguring resection of nasal planum and maxilla than the owner was prepared to accept and may have been associated with an unacceptable morbidity. As an alternative, the extent of disease was reduced using a combination of carboplatin, doxorubicin and piroxicam chemotherapy. This allowed a less extensive nasal planum removal to be performed to remove residual disease with clean margins. The patient achieved a 14 month disease free interval from the time of surgery to the time of local recurrence. Survival time from diagnosis to eventual euthanasia for progressive local disease was 18 months.

Risk of non-small cell lung cancer and the cytochrome P4501A1 Ile462Val polymorphism

Objective: The Ile462Val substitution in the cytochrome P450 1A1 gene (CYP1A1) results in increased enzymatic activity. Preliminary data suggesting a link between this polymorphism and lung cancer risk in Caucasians are inconsistent, reflecting small sample sizes and the relatively low frequency of the variant. Methods: The data set consisted of 1050 primary non-small cell lung cancer cases and 581 controls, a large homogenous population designed specifically to address previous inconsistencies. Patients were genotyped using a PCR-RFLP technique. Results: Carriers of the valine allele, CYP1A1*2C, (Ile/Val or Val/Val genotypes) were significantly over-represented in non-small cell lung cancer compared to controls (OR=1.9; 95% CI=1.2-2.9; p=0.005) when adjusted for confounders, particularly in women (OR=4.6; 95% CI=1.7-12.4; p=0.003). The valine variant was statistically significantly over-represented in cases of lung cancer younger than the median age (64 years) (OR=2.5; 95% CI=1.3-4.8; p=0.005) and cases with less than the median cumulative tobacco-smoke exposure (46 pack-years) (OR=2.4; 95% CI=1.3-4.7; p=0.007). Conclusions: These new data establish an association between the CYP1A1 Ile462Val polymorphism and the risk of developing non-small cell lung cancer, especially among women.

Pathological complete response and residual DCIS following neoadjuvant chemotherapy for breast carcinoma

Patients who have no residual invasive cancer following neoadjuvant chemotherapy for breast carcinoma have a better overall survival than those with residual disease. Many classification systems assessing pathological response to neoadjuvant chemotherapy include residual ductal carcinoma in situ (DCIS) only in the definition of pathological complete response. The purpose of this study was to investigate whether patients with residual DCIS only have the same prognosis as those with no residual invasive or in situ disease. A retrospective analysis of a prospectively maintained database identified 435 patients, who received neoadjuvant chemotherapy for operable breast cancer between February 1985 and February 2003. Of these, 30 (7%; 95% CI 5-9%) had no residual invasive disease or DCIS and 20 (5%; CI 3-7%) had residual DCIS only. With a median follow-up of 61 months, there was no statistical difference in disease-free survival, 80% (95% CI 60-90%) in those with no residual invasive or in situ disease and 61% (95% CI 35-80%) in those with DCIS only (P = 0.4). No significant difference in 5-year overall survival was observed, 93% (95% CI 75-98%) in those with no residual invasive or in situ disease and 82% (95% CI 52-94%) in those with DCIS only (P = 0.3). Due to the small number of patients and limited number of events in each group, it is not possible to draw definitive conclusions from this study. Further analyses of other databases are required to confirm our finding of no difference in disease-free and overall survival between patients with residual DCIS and those with no invasive or in situ disease following neoadjuvant chemotherapy for breast cancer.

Does chemotherapy improve survival in high-risk Stage I and II Merkel cell carcinoma of the skin?

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m(2) i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For disease-specific survival, recurrent disease was the only significant factor. Primary site on the lower limb had an adverse effect on locoregional control. For distant control, the only significant factor was residual disease. Conclusions: The multivariate analysis suggests chemotherapy has no effect on survival, but because of the wide confidence limits, a chemotherapy effect cannot be excluded. A study of this size is inadequately powered to detect small improvements in survival, and a larger randomized study remains the only way to truly confirm whether chemotherapy improves the results in high-risk MCC. (c) 2006 Elsevier Inc.

Stage is not a reliable indicator of tumor volume in non-small cell lung cancer: a preliminary analysis of the trans-tasman radiation oncology group 99-05 database

Background: Tumor volume has been shown to be a prognostic factor for the response of some tumors to radiotherapy. TNM stage has prognostic value for patients treated surgically for non-small cell lung cancer (NSCLC), but its value is less clear for patients treated by nonsurgical means. This may be because tumor size is not a consistent determinant of T stage or stage group. As part of the preliminary analyses for the Trans-Tasman Radiation Oncology Group 99-05 study, the authors performed this analysis to determine to what extent stage reflects tumor volume. Methods: In this prospective multicenter observational study, patients had to have histologically proven NSCLC, no evidence of disease beyond the primary site or thoracic lymph nodes, and been planned for radical radiotherapy with or without chemotherapy. Tumor volume measurements were based on computed tomography-based treatment planning images. Results: Four hundred four patients were available for analysis. There was a strong correlation between (log) maximum tumor diameter and (log) tumor volume (r = 0.93, p < 0.001). Although there was a highly significant trend of increasing volume with increasing T stage and stage group, when tumors were categorized into four groups according to increasing volume, there was only 55% concordance with T stage and 67% concordance with stage group. Conclusions: There is limited correlation between tumor size and disease stage in patients with NSCLC. This justifies documentation and investigation of size as a potential prognostic factor independent of stage. Maximum tumor diameter may be an adequate substitute for volume as a measurement of size.

Turbulence in Small Sub-Tropical Estuary with Semi-Diurnal Tides

In natural estuaries, contaminant transport is driven by the turbulent momentum mixing. The predictions of scalar dispersion can rarely be predicted accurately because of a lack of fundamental understanding of the turbulence structure in estuaries. Herein detailed turbulence field measurements were conducted at high frequency and continuously for up to 50 hours per investigation in a small subtropical estuary with semi-diurnal tides. Acoustic Doppler velocimetry was deemed the most appropriate measurement technique for such small estuarine systems with shallow water depths (less than 0.5 m at low tides), and a thorough post-processing technique was applied. The estuarine flow is always a fluctuating process. The bulk flow parameters fluctuated with periods comparable to tidal cycles and other large-scale processes. But turbulence properties depended upon the instantaneous local flow properties. They were little affected by the flow history, but their structure and temporal variability were influenced by a variety of mechanisms. This resulted in behaviour which deviated from that for equilibrium turbulent boundary layer induced by velocity shear only. A striking feature of the data sets is the large fluctuations in all turbulence characteristics during the tidal cycle. This feature was rarely documented, but an important difference between the data sets used in this study from earlier reported measurements is that the present data were collected continuously at high frequency during relatively long periods. The findings bring new lights in the fluctuating nature of momentum exchange coefficients and integral time and length scales. These turbulent properties should not be assumed constant.

Detailed Measurements during a Transient Front in a Small Subtropical Estuary

High-resolution measurements of velocity and physio-chemistry were conducted before, during and after the passage of a transient front in a small subtropical system about 2.1 km upstream of the river mouth. Detailed acoustic Doppler velocimetry measurements, conducted continuously at 25 Hz, showed the existence of transverse turbulent shear between 300 s prior to the front passage and 1300 s after. This was associated with an increased level of suspended sediment concentration fluctuations, some transverse shear next to the bed and some surface temperature anomaly.

Comparison of BR and QR Eigenvalue Algorithms for Power System Small Signal Stability Analysis

The BR algorithm is a novel and efficient method to find all eigenvalues of upper Hessenberg matrices and has never been applied to eigenanalysis for power system small signal stability. This paper analyzes differences between the BR and the QR algorithms with performance comparison in terms of CPU time based on stopping criteria and storage requirement. The BR algorithm utilizes accelerating strategies to improve its performance when computing eigenvalues of narrowly banded, nearly tridiagonal upper Hessenberg matrices. These strategies significantly reduce the computation time at a reasonable level of precision. Compared with the QR algorithm, the BR algorithm requires fewer iteration steps and less storage space without depriving of appropriate precision in solving eigenvalue problems of large-scale power systems. Numerical examples demonstrate the efficiency of the BR algorithm in pursuing eigenanalysis tasks of 39-, 68-, 115-, 300-, and 600-bus systems. Experiment results suggest that the BR algorithm is a more efficient algorithm for large-scale power system small signal stability eigenanalysis.

High-Frequency Suspended Sediment Flux Measurements in a Small Estuary

In small estuaries, the predictions of scalar dispersion can rarely be predicted accurately because of a lack of fundamental understanding of the turbulence structure. Herein detailed turbulence measurements and suspended sediment concentrations were conducted simultaneously and continuously at high-frequency for 50 hours per investigation in a small subtropical estuary with semi-diurnal tides. The data analyses provided an unique characterisation of the turbulent mixing processes and suspended sediment fluxes. The turbulence was neither homogeneous nor isotropic, and it was not a Gaussian process. The integral time scales for turbulence and suspended sediment concentration were about equal during flood tides, but differed significantly during ebb tides. The field experiences showed that the turbulence measurements must be conducted at high-frequency to characterise the small eddies and the viscous dissipation process, while a continuous sampling was necessary to characterise the time-variations of the instantaneous velocity field, Reynolds stress tensor and suspended sediment flux during the tidal cycles.

Small molecular probes for G-protein-coupled C5a receptors: Conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a

Activation of the human complement system of plasma proteins in response to infection or injury produces a 4-helix bundle glycoprotein (74 amino acids) known as C5a. C5a binds to G-protein-coupled receptors on cell surfaces triggering receptor-ligand internalization, signal transduction, and powerful inflammatory responses. Since excessive levels of C5a are associated with autoimmune and chronic inflammatory disorders, inhibitors of receptor activation may have therapeutic potential. We now report solution structures and receptor-binding and antagonist activities for some of the first small molecule antagonists of C5a derived from its hexapeptide C terminus. The antagonist NMe-Phe-Lys-Pro-D-Cha-Trp-D-Arg-CO2H (1) surprisingly shows an unusually well-defined solution structure as determined by H-1 NMR spectroscopy. This is one of the smallest acyclic peptides found to possess a defined solution conformation, which can be explained by the constraining role of intramolecular hydrogen bonding. NOE and coupling constant data, slow deuterium exchange, and a low dependence on temperature for the chemical shift of the D-Cha-NH strongly indicate an inverse gamma turn stabilized by a D-Cha-NH ... OC-Lys hydrogen bond. Smaller conformational populations are associated with a hydrogen bond between Trp-NH ... OC-Lys, defining a type II beta turn distorted by the inverse gamma turn incorporated within it. An excellent correlation between receptor-affinity and antagonist activity is indicated for a limited set of synthetic peptides. Conversion of the C-terminal carboxylate of 1 to an amide decreases antagonist potency 5-fold, but potency is increased up to 10-fold over 1 if the amide bond is made between the C-terminal carboxylate and a Lys/Orn side chain to form a cyclic analogue. The solution structure of cycle 6 also shows gamma and beta turns; however, the latter occurs in a different position, and there are clear conformational changes in 6 vs 1 that result in enhanced activity. These results indicate that potent C5a antagonists can be developed by targeting site 2 alone of the C5a receptor and define a novel pharmacophore for developing powerful receptor probes or drug candidates.

Analysis of small signal stability margins using genetic optimization

Power system small signal stability analysis aims to explore different small signal stability conditions and controls, namely: (1) exploring the power system security domains and boundaries in the space of power system parameters of interest, including load flow feasibility, saddle node and Hopf bifurcation ones; (2) finding the maximum and minimum damping conditions; and (3) determining control actions to provide and increase small signal stability. These problems are presented in this paper as different modifications of a general optimization to a minimum/maximum, depending on the initial guesses of variables and numerical methods used. In the considered problems, all the extreme points are of interest. Additionally, there are difficulties with finding the derivatives of the objective functions with respect to parameters. Numerical computations of derivatives in traditional optimization procedures are time consuming. In this paper, we propose a new black-box genetic optimization technique for comprehensive small signal stability analysis, which can effectively cope with highly nonlinear objective functions with multiple minima and maxima, and derivatives that can not be expressed analytically. The optimization result can then be used to provide such important information such as system optimal control decision making, assessment of the maximum network's transmission capacity, etc. (C) 1998 Elsevier Science S.A. All rights reserved.