Srinivas Kondalsamy-Chennakesavan

Effect of neuraxial anaesthesia on tumour progression in cervical cancer patients treated with brachytherapy: a retrospective cohort study

BACKGROUND Recent evidence suggests that neuraxial and regional anaesthesia may influence the progression of the underlying malignant disease after surgery. METHODS This retrospective cohort study assessed whether neuraxial anaesthesia would affect the progression of cervical cancer in 132 consecutive patients who were treated with brachytherapy in a tertiary cancer centre in Australia. RESULTS Age, American Society of Anesthesiologists status, International Federation of Gynecologists and Obstetricians (FIGO) cancer staging, invasion into the uterus, tumour volume, and tumour cell types were not significantly different between patients who received neuraxial and general anaesthesia during their first brachytherapy treatment. The use of neuraxial anaesthesia during the first brachytherapy was not associated with a reduced risk of local or systemic recurrence [hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.54-1.67; P=0.863], long-term mortality from tumour recurrence (HR 1.46, 95% CI 0.75-2.84; P=0.265), or all-cause mortality (HR 1.46, 95% CI 0.81-2.61; P=0.209), after adjusting for other prognostic factors. Tumour recurrence and long-term survival were only significantly associated with the tumour cell type, tumour volume, and FIGO tumour staging. Sensitivity analyses using proportions of all brachytherapy sessions performed under neuraxial anaesthesia also did not show any beneficial effects of neuraxial anaesthesia on tumour recurrence and long-term survival. CONCLUSIONS Using neuraxial anaesthesia during brachytherapy for patients with cervical cancer was not associated with a reduced risk of tumour recurrence and mortality when compared with general anaesthesia.

Quantifying the excess risk for proteinuria, hypertension and diabetes in Australian Aborigines : comparison of profiles in three remote communities in the Northern Territory with those in the AusDiab study

Objective: To estimate the magnitude of excess risk for proteinuria, high blood pressure and diabetes in Australian Aboriginal adults in three remote communities by comparing them with nationwide Australian data.

Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer: Results from a randomised controlled trial

AIM To compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety. METHODS Between October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs. RESULTS The incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p<0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2g/L less in the TLH group (p 0.006). CONCLUSIONS Compared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.

Comparative Study of LDR (Manchester System) and HDR Image-guided Conformal Brachytherapy of Cervical Cancer: Patterns of Failure, Late Complications, and Survival

PURPOSE To compare patterns of failure, late toxicities, and survival in locally advanced cervical cancer patients treated by either low-dose-rate (LDR) or conformal high-dose-rate (HDRc) brachytherapy as a part of curative radiotherapy. MATERIALS AND METHODS A retrospective comparative study of 217 advanced cervix cancer patients was conducted; 90 of these patients received LDR and 127 received HDRc brachytherapy. All patients were staged using International Federation of Gynecology and Obstetrics (FIGO) rules, had pretreatment magnetic resonance imaging (MRI), and were treated with concurrent cisplatin chemoradiotherapy. Both groups matched for FIGO stage, MRI tumor volume, and uterine invasion status. RESULTS Local and pelvic failures were similar 12-13% and 14% both in both groups. Abdominal and systemic failures in LDR group were 21% and 24%, whereas corresponding failures in HDRc group were 20% and 24%. Sixty-eight percent (87/127) of patients treated by HDRc remained asymptomatic, whereas 42% (38/90) of patients were asymptomatic from the bowel and bladder symptoms after treatment with LDR. The 5-year OS rate was 60% (SE = 4%). The 5-year failure-free survival rate was 55% (SE = 3%). There was no significant difference between the groups. CONCLUSIONS Image-guided HDRc planning led to a large decrease in late radiation effects in patients treated by HDRc. Patterns of failure and survival were similar in patients treated either by LDR or HDRc.

Anthropometric measurements of Australian Aboriginal adults living in remote areas: Comparison with nationally representative findings

To compare body size measurements in Australian Aboriginals living in three remote communities in the Northern Territory of Australia with those of the general Australian population. Height, weight, waist and hip circumferences and derivative values of body mass index (BMI), waist‐hip ratio (WHR), waist‐height ratio (WHT), and waist‐weight ratios (WWT) of adult Aboriginal volunteers (n = 814), aged 25 to 74 years were compared with participants in the nationally representative ‘AusDiab’ survey (n = 10,434). The Aboriginal body habitus profiles differed considerably from the Australian profile. When compared to Australian females, Aboriginal females were taller and had lower hip circumference but had higher WC, WHR, WHT, and WWT (P < 0.01 for all). When compared with their Australian counterparts, Aboriginal males were shorter, had lower body weight, WC, hip circumference, BMI, and WHT but had higher WHR and WWT (P < 0.001 for all). Significantly more Aboriginal females were classified as overweight and or obese using cutoffs defined by WC and by WHR than by BMI. Aboriginal males were less often overweight and/or obese by BMI than their counterparts, but were significantly more often overweight or obese by WHR. There were significant variations in body size profiles between Aboriginal communities. However, the theme of excess waist measurements relative to their weight was uniform. Aboriginal people had preferential central fat deposition in relation to their overall weight. BMI significantly underestimated overweight and obesity as assessed by waist measurements among Aboriginals. This relationship of preferential central fat deposition to the current epidemic of chronic diseases needs to be explored further. Am. J. Hum. Biol., 2008.

Ultrasound guided conformal brachytherapy of cervix cancer: survival, patterns of failure, and late complications

Objective The aim of this study was to report on the long-term results of transabdominal ultrasound guided conformal brachytherapy in patients with cervical cancer with respect to patterns of failures, treatment related toxicities and survival. Methods Three hundred and nine patients with cervical cancer who presented to Institute between January 1999 and December 2008 were staged with magnetic resonance imaging and positron emission tomography and treated with external beam radiotherapy and high dose rate conformal image guided brachytherapy with curative intent. Follow-up data relating to sites of failure and toxicity was recorded prospectively. Results Two hundred and ninety-two patients were available for analyses. The median (interquantile range) follow-up time was 4.1 years (range, 2.4 to 6.1 years). Five-year failure free survival and overall survival (OS) were 66% and 65%, respectively. Primary, pelvic, para-aortic, and distant failure were observed in 12.5%, 16.4%, 22%, and 23% of patients, respectively. In multivariate analysis, tumor volume and nodal disease related to survival, whereas local disease control and point A dose did not. Conclusion Ultrasound guided conformal brachytherapy of cervix cancer has led to optimal local control and OS. The Melbourne protocol compares favorably to the more technically elaborate and expensive GEC-ESTRO recommendations. The Melbourne protocols technical simplicity with real-time imaging and treatment planning makes this a method of choice for treating patients with cervical cancer.

Differentiating stage 1 epithelial ovarian cancer from benign ovarian tumours using a combination of tumour markers HE4, CA125, and CEA and patient's age.

OBJECTIVE Evaluating the presence of possible malignant disease in women with ovarian masses relies on medical imaging and serum marker findings. This study considers the role of serum Human Epididymal Protein 4 (HE4) antigen in combination with other serum markers to more effectively estimate the risk of malignancy in patients with isolated pelvic masses. METHODS We used prospectively collected biospecimens held by the Australian Ovarian Cancer Study (AOCS). Serum samples of patients with FIGO stage 1 epithelial ovarian cancer or with a benign condition were analysed for levels of circulating HE4 antigen, CA 125, and CEA, and test results were used to predict the presence of malignancy and to differentiate benign from malignant pelvic masses. RESULTS HE4 levels were significantly elevated amongst postmenopausal women and amongst patients with malignancy compared to premenopausal women and those with benign disease (p<0.001 for both). The combination of CA125 and age, achieved an area under the ROC curve of 0.677 (95% CI: 0.584 to 0.770, p=0.778), whilst HE4+CA125+CEA in combination with patients age showed significantly higher AUC of 0.797 (95% CI: 0.721 to 0.874, p=0.0052). By adjusting the ROMA cut-off values the percentage of correctly classified premenopausal patients into low and high risk groups increased from 36.99% to 69.86%. CONCLUSIONS In patients with isolated pelvic masses, the combination of HE4, CA 125 and age with or without CEA provides higher diagnostic value compared to CA125 and age alone. It may therefore be considered for continuous evaluation in patients with adnexal masses.

Comparison of Measurements of the Uterus and Cervix Obtained by Magnetic Resonance and Transabdominal Ultrasound Imaging to Identify the Brachytherapy Target in Patients With Cervix Cancer

PURPOSE To compare measurements of the uterus and cervix obtained with magnetic resonance imaging (MRI) and transabdominal ultrasound to determine whether ultrasound can identify the brachytherapy target and be used to guide conformal brachytherapy planning and treatment for cervix cancer. METHODS AND MATERIALS Consecutive patients undergoing curative treatment with radiation therapy between January 2007 and March 2012 were included in the study. Intrauterine applicators were inserted into the uterine canal while patients were anesthetized. Images were obtained by MRI and transabdominal ultrasound in the longitudinal axis of the uterus with the applicator in treatment position. Measurements were taken at the anterior and posterior surface of the uterus at 2.0-cm intervals along the applicator, from the external os to the tip of the applicator. Data were analyzed using Bland Altman plots examining bias and 95% limits of agreement. RESULTS A total of 192 patients contributed 1668 measurements of the cervix and uterus. Mean (± SD) differences of measurements between imaging modalities at the anterior and posterior uterine surface ranged from 1.5 (± 3.353) mm to 3.7 (± 3.856) mm, and -1.46 (± 3.308) mm to 0.47 (± 3.502) mm, respectively. The mean differences were less than 3 mm in the cervix. The mean differences were less than 1.5 mm at all measurement points on the posterior surface. CONCLUSION Differences in the measurements of the cervix and uterus obtained by MRI and ultrasound were within clinically acceptable limits. Transabdominal ultrasound can be substituted for MRI in defining the target volume for conformal brachytherapy treatment of cervix cancer.

Nomograms to predict isolated loco-regional or distant recurrence among women with uterine cancer

OBJECTIVE While there is ample literature on prognostic factors for uterine cancer, currently there are nomeans to estimate an individuals risk for recurrence or to differentiate the risk of loco-regional recurrence from distant recurrence. We addressed this gap by developing nomograms to individualize the risk of recurrence. METHODS A total of 2097 consecutive patients who underwent primary surgery between 1997 and 2007 were included. Sixteen covariates were evaluated for their prognostic significance and modeled using multivariable competing risks regression to predict three-year outcomes as part of a nomogram. Each covariate in the nomogram is assigned a value, and a sum of these values form the overall risk score from which three-year incidence probabilities can be predicted for each individual. Predictive accuracy was assessed with concordance index and then corrected for optimism. RESULTS The median follow-up time (inter-quartile range, IQR) was 50.0 (28.3-77.5) months and 221 patients developed a recurrence (127 patients with isolated loco-regional recurrence, 94 patients with distant recurrence). The nomograms included the following covariates: age at diagnosis, FIGO stage (2009), grade, lymphovascular invasion, histological type, depth of myometrial invasion, and peritoneal cytology. Concordance indices for isolated loco-regional and distant recurrences were 0.73 and 0.86, respectively. CONCLUSIONS Our nomograms quantify an individual patients risk of isolated loco-regional and distant recurrence, using factors that are routinely collected. They may assist clinicians to assess an individuals prognosis, individualize treatment and also assist in the risk stratification in prospective randomized clinical trials evaluating the effectiveness of treatments for uterine cancer.

Determinants of rural practice: positive interaction between rural background and rural undergraduate training

Objective: To determine the role of rural background and years of rural clinical school training on subsequent rural clinical practice.