Perioperative cell-free DNA trends predict recurrence of non-metastatic colorectal cancer significantly earlier than CEA trends over the first 2 years post-operatively in stage II and stage III colon cancer.

PURPOSE: We aimed to compare the diagnostic accuracy of perioperative ΔcfDNA to ΔCEA (over the first 2 years post-operatively) for identifying disease recurrence in colon cancer. METHODS: Patients presenting for elective resection for colon cancer with curative intent were screened for inclusion. Perioperative cfDNA levels were measured at seven different times points(pre-operative and post-operative at 3 h, 6 h, 24 h, 48 h, POD3 and POD5). CEA levels were measured on the same patients up to 2 years post-operatively. Change in trend (Δ) was defined as the ß coefficient using a logistic regression model. Statistical analysis was performed using SPSS, version 23. RESULTS: Longitudinal data on twenty-two patients were analysed (n = 16 male, n = 6 female) for a median of 29 months (IQR 23 months) during which time three patients developed (distant) recurrence. Perioperative ΔcfDNA at 48Hrs, POD3 and POD5 were significantly associated with early recurrence. ΔCEA was significantly associated with early recurrence at 6 months, 1 year and 2 years post-operatively, only when disease recurrence was macroscopically established. ΔcfDNA was associated with an area under the curve (AUC) of 0.947 (95% CI 0.88-1.0, p < 0.001) and ΔCEA was associated with an AUC of 0.9382 (95%CI 0.88-0.99, p < 0.0001). This translated into a specificity of 97% (95%CI 86.51-99.87%) for ΔcfDNA and 77.5% sensitivity (95%CI 62.5-87.7%) in the immediate perioperative period and an 88.9% specificity (95%CI 56.5-99.4%) and 76.5% sensitivity (95%CI 63.24-86%) for ΔCEA over the first 2 years post-operatively. CONCLUSIONS: In this pilot study, following curative resection for colon cancer changing trends in perioperative cfDNA (ΔcfDNA) identify those at risk of recurrent disease before recurrence develops which is at least 6 months earlier than CEA changes (ΔCEA) which are only observed when recurrence is established.

Risk of colorectal cancer associated with BRCA1 and/or BRCA2 mutation carriers: systematic review and meta-analysis.

BACKGROUND: Carriers of the BRCA1 and/or BRCA2 mutation incur a lifetime risk of up to 85 per cent for breast cancer, and between 20 and 40 per cent for ovarian cancer. Efforts to estimate the lifetime risk of developing colorectal cancer for BRCA mutation carriers have produced conflicting results. Consequently, there are no formal guidelines regarding the need for bowel screening for individuals with BRCA1 and/or BRCA2 mutations. This systematic review and meta-analysis determined the risk of colorectal cancer associated with BRCA carrier mutations. METHODS: The primary outcome was incidence of colorectal cancer in BRCA mutation carriers. Secondary outcomes were the incidence in BRCA1 and BRCA2 carriers, Ashkenazi Jews, and age- and sex-matched cohorts. RESULTS: Eleven studies were included in the review, with an overall population of 14 252 and 4831 colorectal cancers identified. Nine studies were included in the meta-analysis. There was no increase in colorectal cancer among patients carrying a BRCA mutation (odds ratio 1·03, 95 per cent c.i. 0·80 to 1·32; P = 0·82). After adjustment for Ashkenazi heritage, and age and sex estimates, there was no increased odds of developing colorectal cancer (with no heterogeneity, I2  = 0 per cent). CONCLUSION: BRCA1 and/or BRCA2 mutation carriers are not at a higher risk of colorectal cancer.

ANTECEDENTES: Las portadoras de la mutación BRCA1 y/o BRCA2 presentan un riesgo a lo largo de la vida de hasta un 85% para presentar un cáncer de mama y entre 20-40% para el cáncer de ovario. Los esfuerzos para estimar el riesgo de desarrollar cáncer colorrectal (colorectal cancer, CCR) a lo largo de la vida en portadoras de mutaciones BRCA han dado resultados contradictorios. En consecuencia, no existen pautas formales con respecto a la necesidad de realizar el cribado de CRC en personas portadoras de mutaciones BRCA1 y/o BRCA2. Esta revisión sistemática y metaanálisis analiza el riesgo de CRC asociado en pacientes portadoras de mutaciones BRCA. MÉTODOS: Se incluyeron nueve estudios en el metaanálisis. La población general del estudio fue de 18.839 pacientes, con 4.978 con CRC identificado. La variable principal fue la incidencia de cáncer colorrectal en portadoras de mutaciones BRCA. Las variables secundarias incluyeron el análisis de la incidencia de subgrupos en BRCA 1, BRCA 2, etnia judía Ashkenazi y cohortes emparejadas por edad y sexo. RESULTADOS: No hubo un aumento de CRC en pacientes con una mutación BRCA (razón de oportunidades, odds ratio, OR 1,03; i.c. del 95% 0,80-1,32; P = 0,82). Cuando se ajustó de acuerdo con la ascendencia Ashkenazi y las estimaciones de edad y sexo, no hubo mayores probabilidades de desarrollar cáncer colorrectal (sin heterogeneidad en los estudios (I2 = 0)). CONCLUSIÓN: Este metaanálisis concluye que el riesgo de cáncer colorrectal no fue significativamente mayor en las portadoras de mutaciones BRCA1 y/o BRCA2. Sin embargo, se requiere más evidencia antes de no recomendar la colonoscopia de cribado a las portadoras de la mutación BRCA1/2. Las pruebas de inmunoquímica fecal pueden ser una alternativa apropiada en esta población.

Meta-analysis of the diagnostic accuracy of ultrasound-guided fine-needle aspiration and core needle biopsy in diagnosing axillary lymph node metastasis.

BACKGROUND: Axillary lymph node status remains a significant prognostic indicator in breast cancer. Here, the diagnostic accuracy of ultrasound-guided fine-needle aspiration (US-FNA) and ultrasound-guided core needle biopsy (US-CNB) in axillary staging was compared. METHODS: A comprehensive search was undertaken of all published studies comparing the diagnostic accuracy of US-CNB and US-FNA of axillary lymph nodes in breast cancer. Studies were included if raw data were available on the diagnostic performance of both US-FNA and US-CNB, and compared with final histology results. Relevant data were extracted from each study for systematic review. Meta-analysis was performed using a random-effects model. The pooled sensitivity and specificity of US-FNA and US-CNB were obtained using a bivariable model. Summary receiver operating characteristic (ROC) graphs were created to confirm diagnostic accuracy. RESULTS: Data on a total of 1353 patients from six studies met the inclusion criteria and were included in the final analysis. US-CNB was superior to US-FNA in diagnosing axillary nodal metastases: sensitivity 88 (95 per cent c.i. 84 to 91) versus 74 (70 to 78) per cent respectively. Both US-CNB and US-FNA had a high specificity of 100 per cent. Reported complication rates were significantly higher for US-CNB compared with US-FNA (7·1 versus 1·3 per cent; P < 0·001). Conversely, the requirement for repeat diagnostic procedures was significantly greater for US-FNA (4·0 versus 0·5 per cent; P < 0·001). CONCLUSION: US-CNB is a superior diagnostic technique to US-FNA for axillary staging in breast cancer.

Health literacy and the perception of risk in a breast cancer family history clinic.

BACKGROUND: Informed consent is an essential component of medical practice, and especially so in procedural based specialties which entail varying degrees of risk. Breast cancer is one of the most common cancers in women, and as such is the focus of extensive research and significant media attention. Despite this, considerable misperception exists regarding the risk of developing breast cancer. AIMS: This study aims to examine the accuracy of risk perception of women attending a breast cancer family history clinic, and to explore the relationship between risk perception accuracy and health literacy. METHODS: A cross-sectional study of women attending a breast cancer family history clinic (n = 86) was carried out, consisting of a patient survey and a validated health literacy assessment. Patients' perception of personal and population breast cancer risk was compared to actual risk as calculated by a validated risk assessment tool. RESULTS: Significant discordance between real and perceived risks was observed. The majority (83.7%) of women overestimated their personal lifetime risk of developing breast cancer, as well as that of other women of the same age (89.5%). Health literacy was considered potentially inadequate in 37.2% of patients; there was a correlation between low health literacy and increased risk perception inaccuracy across both personal ten-year (rs = 0.224, p = 0.039) and general ten-year population estimations. (rs = 0.267, p = 0.013). CONCLUSION: Inaccuracy in risk perception is highly prevalent in women attending a breast cancer family history clinic. Health literacy inadequacy is significantly associated with this inaccuracy.

An International Multicenter Review of the Malignancy Rate of Excised Papillomatous Breast Lesions.

BACKGROUND: Papillary lesions of the breast are a relatively rare, but heterogeneous group ranging from benign to atypical and malignant. Debate exists regarding the optimal management of these lesions. In the absence of more accurate risk-stratification models, traditional management guidelines recommend surgical excision, despite the majority of lesions proving benign. This study sought to determine the rate of malignancy in excised breast papillomas and to elucidate whether there exists a population in which surgical excision may be unnecessary. METHODS: A multicenter international retrospective review of core biopsy diagnosed breast papillomas and papillary lesions was performed between 2009 and 2013, following institutional ethical approval. Patient demographics, histopathological, and radiological findings were recorded. All data was tabulated, and statistical analysis performed using Stata. RESULTS: A total of 238 patients were included in the final analysis. The age profile of those with benign pathology was significantly younger than those with malignant pathology (p < 0.001). Atypia on core needle biopsy was significantly associated with a final pathological diagnosis of malignancy (OR = 2.73). The upgrade rate from benign core needle biopsy to malignancy on the final pathological sample was 14.4 %; however, only 3.7 % had invasive cancer. CONCLUSIONS: This international dataset is one of the largest in the published literature relating to breast papillomas. The overall risk of malignancy is significantly associated with older age and the presence of atypia on core needle biopsy. It may be possible to stratify higher-risk patients according to age and core needle biopsy findings, thereby avoiding surgery on low-risk patients.

A meta-analysis to determine the oncological implications of conversion in laparoscopic colorectal cancer surgery.

AIM: Laparoscopic colon and rectal cancer surgery is oncologically equivalent to open resection, but the impact of conversion is undetermined. The aim of this study was to assess the oncological outcome and predictive factors associated with conversion. METHOD: A comprehensive search for published studies examining the associated factors and outcome of conversion from laparoscopic to open colorectal cancer resection was performed adhering to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Only randomized control trials and prospective studies were included. Each study was reviewed and the data extracted. Random effects methods were used to combine data. RESULTS: Fifteen studies, including 5293 patients, met the inclusion criteria. Of these 4391 patients had a completed laparoscopic resection and 902 were converted to an open resection. The average conversion rate of the studies was 17.9 ± 10.1%. Meta-analysis showed completed laparoscopic surgery favoured lower 30-day mortality (OR 0.134, 95% CI 0.047-0.385, P < 0.0001), lower long-term disease recurrence (OR 0.634, 95% CI 0.421-0.701, P < 0.023) and lower overall mortality (OR 0.512, 95% CI 0.417-0.629, P < 0.0001). Factors negatively associated with completion of laparoscopic surgery were male gender (P = 0.011), rectal tumour (P = 0.017), T3/T4 tumour (P = 0.009) and node-positive disease (P = 0.009). Completed laparoscopic surgery was also associated with a lower body mass index (BMI; mean difference -0.93 kg/m(2) , P = 0.004). CONCLUSION: The results suggest that conversion from laparoscopic to open colorectal cancer resection is influenced by patient and tumour characteristics and is associated with an adverse perioperative outcome. Although confounding factors such as advanced tumour stage and elevated BMI are present, unsuccessful laparoscopic surgery appears to be associated with an adverse long-term oncological outcome.

"Is general surgery still relevant to the subspecialised trainee?" A 10 year comparison of general versus specialty surgical practice.

BACKGROUND: The splintering of general surgery into subspecialties in the past decade has brought into question the relevance of a continued emphasis on traditional general surgical training. With the majority of trainees now expressing a preference to subspecialise early, this study sought to identify if the requirement for proficiency in managing general surgical conditions has reduced over the past decade through comparison of general and specialty surgical admissions at a tertiary referral center. METHODS: A cross-sectional review of all surgical admissions at Cork University Hospital was performed at three individual time points: 2002, 2007 & 2012. Basic demographic details of both elective & emergency admissions were tabulated & analysed. Categorisation of admissions into specialty relevant or general surgery was made using International guidelines. RESULTS: 11,288 surgical admissions were recorded (2002:2773, 2007:3498 & 2012:5017), showing an increase of 81 % over the 10-year period. While growth in overall service provision was seen, the practice of general versus specialty relevant emergency surgery showed no statistically significant change in practice from 2002 to 2012 (p = 0.87). General surgery was mostly practiced in the emergency setting (84 % of all emergency admissions in 2012) with only 28 % elective admissions for general surgery. A reduction in length of stay was seen in both elective (3.62-2.58 bed days, p = 0.342) & emergency admissions (7.36-5.65, p = 0.026). CONCLUSIONS: General surgical emergency work continues to constitute a major part of the specialists practice. These results emphasize the importance of general surgical training even for those trainees committed to sub-specialisation.

Less stress, more success? Oncological implications of surgery-induced oxidative stress.

Reactive oxygen species (ROS) possess important cell signalling properties. This contradicts traditional thought which associated ROS activity with cell death. Emerging evidence clearly demonstrates that ROS signalling acts as a key regulator in tumour cell survival and in the cellular processes required for tumour cells to successfully metastasise and proliferate. The discovery of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) family of enzymes in the last decade has unravelled much of the mystery surrounding how ROS are generated. Tumour cells are now known to express Nox enzymes which produce ROS required for cellular signalling. Activation of Nox enzymes occurs via interaction with proinflammatory cytokines and growth factors, all of which are released following surgical trauma. As our understanding of the signalling capabilities of ROS grows, the oncological implications of ROS activity are gradually being revealed. Nox-derived ROS are known to play a central role in each step of the metastatic cascade including invasion, adhesion, angiogenesis and proliferation. This article describes how surgery creates a ROS-rich environment, which facilitates redox signalling, and also examines the role played by Nox enzymes in this process. The authors then explore current knowledge of the oncological implications of surgery-induced redox signalling, and discuss current and future therapeutic strategies targeted at ROS and Nox enzymes in cancer patients.

Rapid on-site evaluation of axillary fine-needle aspiration cytology in breast cancer.

BACKGROUND: Axillary ultrasonography (AUS) and fine-needle aspiration cytology (FNAC) can establish axillary lymph node status before surgery, although this technique is hampered by poor adequacy rates. To achieve consistently high rates of FNAC adequacy, rapid on-site evaluation (ROSE) of FNAC samples was introduced. METHODS: This single-centre, retrospective observational study of patients with newly diagnosed breast cancer undergoing preoperative AUS and FNAC between February 2008 and November 2010 examined the effect of the introduction of ROSE. RESULTS: A total of 381 patients were included. AUS revealed 152 axillae with suspicious radiological features. FNAC was positive for malignant cells in 75 (49·3 per cent) of 152 samples. Sentinel lymph node mapping was avoided in 75 patients, representing 19·7 per cent of the entire study population. Adequacy rates increased from 78 per cent to 96 per cent following the introduction of ROSE (P = 0·001). The overall sensitivity and specificity of AUS and FNAC was 80·6 and 100 per cent respectively. A lymph node diameter equal to or larger than 10 mm and extranodal extension were significantly associated with positive FNAC (P < 0·001 and P = 0·012 respectively). Maximum lymph node diameter of at least 10 mm was an independent predictor of positive FNAC (odds ratio 11·2, 95 per cent confidence interval 3·32 to 37·76; P < 0·001). CONCLUSION: AUS with FNAC provided accurate preoperative staging of the axilla for metastatic breast disease and avoided unnecessary sentinel lymph node mapping. The introduction of ROSE ensured the efficiency of AUS and FNAC.

Current evidence for human yersiniosis in Ireland.

Yersiniosis associated with abdominal pain was commonly reported in Ireland in the 1980s. However, the Health Protection Surveillance Centre (HPSC) currently records only three to seven notified cases of yersiniosis per year. The most common cause of yersiniosis worldwide is Yersinia enterocolitica, and the leading source for this organism is consumption of pork-based food products. In contrast to the apparent current scarcity of yersiniosis cases in humans in Ireland, pathogenic Y. enterocolitica are detectable in a high percentages of pigs. To establish whether the small number of notifications of human disease was an underestimate due to lack of specific selective culture for Yersinia, we carried out a prospective culture study of faecal samples from outpatients with diarrhoea, with additional culture of throat swabs, appendix swabs and screening of human sewage. Pathogenic Yersinia strains were not isolated from 1,189 faeces samples, nor from 297 throat swabs, or 23 appendix swabs. This suggested that current low notification rates in Ireland are not due to the lack of specific Yersinia culture procedures. Molecular screening detected a wider variety of Y. enterocolitica-specific targets in pig slurry than in human sewage. A serological survey for antibodies against Yersinia YOP (Yersinia Outer Proteins) proteins in Irish blood donors found antibodies in 25 %, with an age-related trend to increased seropositivity, compatible with the hypothesis that yersiniosis may have been more prevalent in Ireland in the recent past.

Effects of abdominal fat distribution parameters on severity of acute pancreatitis.

BACKGROUND: Obesity is a well-established risk factor for acute pancreatitis. Increased visceral fat has been shown to exacerbate the pro-inflammatory milieu experienced by patients. This study aimed to investigate the relationship between the severity of acute pancreatitis and abdominal fat distribution parameters measured on computed tomography (CT) scan. METHODS: Consecutive patients admitted to Cork University Hospital with acute pancreatitis between January 2005 and December 2010 were evaluated for inclusion in the study. An open source image analysis software (Osirix, v 3.9) was used to calculate individual abdominal fat distribution parameters from CT scans by segmentation of abdominal tissues. RESULTS: A total of 214 patients were admitted with pancreatitis between January 2005 and December 2010. Sixty-two of these patients underwent a CT scan and were thus eligible for inclusion. Visceral fat volume was the volumetric fat parameter that had the most significant association with severe acute pancreatitis (P = 0.003). There was a significant association between visceral fat volume and subsequent development of systemic complications of severe acute pancreatitis (P = 0.003). There was a strong association between mortality and visceral fat volume (P = 0.019). Multivariate regression analysis, adjusted for gender, did not identify any individual abdominal fat distribution index as an independent risk factor for severe acute pancreatitis. CONCLUSIONS: Overall, estimation of abdominal fat distribution parameters from CT scans performed on patients with acute pancreatitis indicates a strong association between visceral fat, severe acute pancreatitis, and the subsequent development of systemic complications. These data suggest that visceral fat volume should be incorporated into future predictive scoring systems.

The role of sentinel lymph node biopsy in patients with thick melanoma. A single centre experience.

AIMS: To evaluate the role, if any, of sentinel lymph node mapping (SLNM) with biopsy (SLNB) in patients with thick cutaneous melanoma. METHODS: Consecutive patients with thick (Breslow ≥4 mm) cutaneous melanoma, undergoing SLNB were identified from a departmental database comprising 550 patients in total from 2000 to 2010. Factors examined included demographic data, histological subtype, site and depth of lesion, percentage of positive SLNs, regional recurrence in the setting of a negative SLNB result (false-negative rate), complications, further lymphadenectomy, and follow-up (disease free and overall survival), where available. RESULTS: Sixty-four eligible patients (37 men, 27 women) underwent primary excision and SLNM. Median patient age was 59 years (range 8-82 years). Mean Breslow depth was 7 mm (range 4-19 mm). Thirty melanomas were located on the limbs, 19 on the head and neck and 15 on the trunk. Twenty-three (35%) were ulcerated. Of the 57 patients who had a sentinel node identified, 18 (31%) had metastatic melanoma identified. The mean survival time for patients with a negative SLN was 79 months versus 18 months for those with a positive node. Patients with a negative SLN have a 5 year disease free survival of 79% versus 11% (p < 0.001) and an overall 5 year survival rate of 85% versus 32% when compared to node positive patients. CONCLUSIONS: The status of the SLN is predictive of disease recurrence and overall survival in patients with a thick primary cutaneous melanoma. This modality should be employed, where applicable, in this cohort of patients.

Changes in outcome and management of perforated diverticulitis over a 10 year period.

INTRODUCTION: Aggressive non-operative intervention and evolving surgical strategies have altered the treatment of perforated diverticulitis in the acute setting. These strategies have predominantly been implemented over the last decade. The aim of this study was to assess the impact of this on patient outcome during their index admission and subsequently. METHODS: Consecutive patients admitted with acute diverticulitis between 1999 and 2010 were identified. Patient demographics, treatment strategies and outcomes were collected and analysed. Patients who had an episode of perforated diverticulitis during their index admission were followed. RESULTS: 739 patients were admitted with acute diverticulitis. Of these, 115 (15.7%) had perforated diverticulitis. 53 (47.8%) underwent an intervention. There was a reduction in the mean age of patients admitted with acute diverticulitis of 8.9% over the study period (p = 0.002). There was a significant increase in the use of CT scanning pre-operatively (p < 0.001). 'Non-resectional' interventions have emerged in the form of laparoscopic lavage (n = 5) and percutaneous abscess drainage (n = 14). There was associated improved length of stay (p < 0.001). CONCLUSION: Outcomes for patients with perforated diverticulitis have improved, contributed to in part by an increased use of non-resectional management strategies.

A descriptive study of consent documentation.

The aim of this study was to observe the error rate in the consent process of a university hospital and to illicit the opinions of the consenting doctors on the process. A prospective observational review of theatre consent forms was performed along with an anonymous survey of non-consultant hospital doctors (NCHD's). No potential risks were documented in 95.3% of the 64 scrutinized consents and late alterations were required in 9%. Respondents to the NCHD survey estimated that they were unsure of the procedure or risks involved in an average of 29% of occasions. Interns admitted to being unsure of the details of the procedure in almost a third (32%) of cases, making them less well informed than their senior colleagues (p=0.024). This study highlights the difficulties encountered by consenting doctors, an issue which may lead to patient dissatisfaction, threaten the efficient running of a surgical unit and potentially expose its staff to avoidable litigation. It also recommends the use of multimedia adjuncts to facilitate both patient and doctor education in the consent process.

Primary hyperparathyroidism causing posterior reversible encephalopathy syndrome: a case report.

Posterior reversible encephalopathy syndrome (PRES) is a reversible leukoencephalopathy characterised by subcortical vasogenic oedema and neurological signs. We present the case of a 64-year-old woman who presented to hospital with symptomatic primary hyperparathyroidism. Her parathyroid hormone (PTH) level on admission was elevated at 1,330ng/l (normal range15-68ng/l) and her serum calcium measured 4.83mmol/l (normal range 2.25-2.54mmol/l). Technectium-99m sestamibi scan demonstrated a focus of radiotracer uptake consistent with a right upper parathyroid adenoma or carcinoma. After commencing appropriate medical treatment, the patient developed intractable seizures necessitating endotracheal intubation. Magnetic resonance imaging of her brain revealed bilateral symmetrical T2 hyperintensities in the posterior circulation consistent with PRES. Following stabilisation and further medical treatment for hypercalcaemia, the patient underwent a parathyroidectomy. Preoperative rapid PTH assay measured 1,021ng/l. Following excision, PTH levels fell to just 10ng/l. She was extubated in the intensive care unit on postoperative day 1 and made an uneventful recovery. At her 6-week follow-up appointment, all neurological symptoms had resolved. PRES is a rare neurological entity more often seen in the setting of hypertension, immunosuppression and renal failure. The development of new neurological manifestations in the setting of known risk factors should raise suspicion for the underlying diagnosis.

Routine calcium measurement is not necessary after most thyroid surgeries: a prospective clinical study.

OBJECTIVES: Calcium levels are often measured to diagnose postoperative hypocalcaemia following thyroidectomy. The aims of this study were to (i) prospectively determine the incidence of symptomatic and biochemical hypocalcaemia following thyroidectomy, (ii) to identify if any associations exist between hypocalcaemia, type of surgery, histological diagnosis, specimen size/weight and the presence of histological parathyroid tissue and (iii) to evaluate the necessity of routine measurement of calcium levels following all thyroidectomies. DESIGN: Prospective clinical study. SETTINGS: University teaching hospital. PARTICIPANTS: Eighty-six patients presenting consecutively for thyroid surgery. OUTCOME MEASURES: Type of surgery, indications, perioperative calcium levels, symptoms of hypocalcaemia and histology were documented. RESULTS: Fifty-four patients underwent thyroid lobectomy and isthmusectomy, 19 underwent total and 13 completion thyroidectomy. Significantly, no patient undergoing thyroid lobectomy developed hypocalcaemia versus 26% of total thyroidectomies (P=0.001) and 23% of completion thyroidectomies (P=0.006). All eight patients with hypocalcaemia required treatment. Seven were initially identified clinically. Logistic regression analysis revealed that operation type was the only independent risk factor for developing hypocalcaemia (P=0.021). CONCLUSIONS: No patient developed hypocalcaemia following thyroid lobectomy and isthmusectomy. Considering the majority (63%) of thyroid surgeries were lobectomies, most patients tested appear low risk for hypocalcaemia. Definitive prediction of hypocalcaemia postoperatively remains a challenge. However, our results suggest that analysing calcium levels routinely following thyroid lobectomy is unwarranted.

Association between thyroid nodule size and malignancy rate.

INTRODUCTION: The diagnostic performance of ultrasound-fine needle aspiration to identify thyroid nodules harbouring malignancy remains variable. The aim of this study was to determine thyroid nodule size and cytological classification as predictors of malignancy risk. MATERIALS AND METHODS: We conducted a retrospective cohort analysis at an academic hospital involving 499 consecutive patients who underwent thyroid surgery between 2004 and 2015. RESULTS: A total of 503 thyroid nodules (499 patients, 84% female; mean age 50.8 years, standard deviation, SD, 15.4 years) were analysed. Of these, 19.5% were malignant. The mean (± SD) nodule size was 3.28 ± 1.63 cm and 3.27 ± 1.54 cm for benign and malignant nodules, respectively. The odds of malignancy for thyroid nodules less than 3.0 cm was similar to those for nodules of 3.0 cm or greater (0.26 compared with 0.29; p=0.77). Overall, the sensitivity and specificity of fine-needle aspiration in this cohort were 71.4% and 100%, respectively. The overall false negative rate was 5.4%. When the cut-off of 3.0 cm was used, the false negative rate in thyroid nodules less than 3.0 cm was 0% compared with 7.0% in nodules of 3.0 cm or greater. Thus, class (p<0.01) but not nodule size (p=0.49), was associated with higher malignancy risk. CONCLUSIONS: Our results suggest that thyroid nodule size did not accurately predict the risk of thyroid malignancy irrespective of fine-needle aspiration cytology. Routine diagnostic thyroid lobectomy solely owing to thyroid nodule size of 3.0 cm or greater is currently not justified.

Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.

Analysis of differential gene expression in colorectal cancer and stroma using fluorescence-activated cell sorting purification.

Tumour stroma gene expression in biopsy specimens may obscure the expression of tumour parenchyma, hampering the predictive power of microarrays. We aimed to assess the utility of fluorescence-activated cell sorting (FACS) for generating cell populations for gene expression analysis and to compare the gene expression of FACS-purified tumour parenchyma to that of whole tumour biopsies. Single cell suspensions were generated from colorectal tumour biopsies and tumour parenchyma was separated using FACS. Fluorescence-activated cell sorting allowed reliable estimation and purification of cell populations, generating parenchymal purity above 90%. RNA from FACS-purified and corresponding whole tumour biopsies was hybridised to Affymetrix oligonucleotide microarrays. Whole tumour and parenchymal samples demonstrated differential gene expression, with 289 genes significantly overexpressed in the whole tumour, many of which were consistent with stromal gene expression (e.g., COL6A3, COL1A2, POSTN, TIMP2). Genes characteristic of colorectal carcinoma were overexpressed in the FACS-purified cells (e.g., HOX2D and RHOB). We found FACS to be a robust method for generating samples for gene expression analysis, allowing simultaneous assessment of parenchymal and stromal compartments. Gross stromal contamination may affect the interpretation of cancer gene expression microarray experiments, with implications for hypotheses generation and the stability of expression signatures used for predicting clinical outcomes.

A definitive role for sentinel lymph node mapping with biopsy for cutaneous melanoma of the head and neck.

AIMS: The aim of this study was to evaluate the role, if any, of sentinel lymph node mapping (SLNM) with biopsy (SLNB) in patients with cutaneous melanoma of the head and neck. METHODS: Consecutive patients with cutaneous melanoma of the head and neck regions undergoing SLNM with biopsy were identified from a departmental database comprising 480 patients in total from 2000-2007. Factors examined included demographic data, histological subtype, site and depth of lesion, pre-operative lymphoscintigraphy, percentage of positive SLNs, regional recurrence in the setting of a negative SLNB result (false-negative rate), complications, further lymphadenectomy, percentage of skin grafting required and follow-up. RESULTS: The median patient age was 51 years (range 18-90 years). The mean Breslow depth was 3.25 mm (range 1-19 mm). Five patients presented with stage III/IV disease. A SLN was identified in 27/40 patients who underwent head and neck SLN mapping (mean two lymph nodes per patient). Of these, six (22%) patients were positive for metastatic melanoma. The false-negative rate was 9.5%. The median follow up for patients was 39.6 months (range 12-96 months). No facial nerve injury or other major morbidity occurred. CONCLUSIONS: This study indicates that SLNB is a reliable and safe technique to diagnose regional spread from head and neck cutaneous melanoma. It is more difficult than at other sites. These lesions have a higher incidence of failed SLN mapping and a higher rate of recurrence following negative SLNB, when compared to truncal and extremity lesions. Nodular melanomas are more likely to fail the sentinel lymph node mapping procedure than other histological subtypes.