Right-side fixation of the sigmoid colon causing internal herniation with closed-loop obstruction of both small and large bowel: a case report and review of the literature.

BACKGROUND: Right-side fixation of the sigmoid colon is a rare anatomical variant associated with intestinal malrotation (Choi et al. in J Korean Surg Soc. 84(4):256-60, 2013). Differently from other forms of malrotation, this variant has not been associated thus far with acute surgical conditions. CASE PRESENTATION: In this report, we present a 65-year-old Caucasian patient admitted for bowel obstruction symptoms. Computed tomography scan revealed right-side fixation of the sigmoid colon extended to the subhepatic recess complicated by obstructed internal herniation of the ileum. In this patient, the sigmoid colon occupied a recess posterior to the ascending colon and right Toldt's fascia. Within this narrow anatomical space, an ileal loop was trapped causing internal herniation with resultant close-bowel obstruction of both ileum and sigmoid colon. The ileal loop was released surgically and the anatomical abnormality corrected. CONCLUSIONS: To our knowledge, this is the first case of right-side fixation of the sigmoid colon causing acute obstruction secondary to internal herniation of the small intestine. Early recognition and precise anatomical definition of such anatomical variants are essential to optimize their surgical approach.

OVPSYCH2: A randomized controlled trial of psychological support versus standard of care following chemotherapy for ovarian cancer.

BACKGROUND: Fear of disease progression (FOP) is a rational concern for women with Ovarian Cancer (OC) and depression is also common. To date there have been no randomized trials assessing the impact of psychological intervention on depression and FOP in this patient group. PATIENTS AND METHODS: Patients with primary or recurrent OC who had recently completed chemotherapy were eligible if they scored between 5 and 19 on the PHQ-9 depression and were randomized 1:1 to Intervention (3 standardized CBT-based sessions in the 6-12 weeks post-chemotherapy) or Control (standard of care). PHQ-9, FOP-Q-SF, EORTC QLQ C30 and OV28 questionnaires were then completed every 3 months for up to 2 years. The primary endpoint was change in PHQ-9 at 3 months. Secondary endpoints were change in other scores at 3 months and all scores at later timepoints. RESULTS: 182 patients registered; 107 were randomized; 54 to Intervention and 53 to Control; mean age 59 years; 75 (70%) had completed chemotherapy for primary and 32 (30%) for relapsed OC and 67 patients completed both baseline and 3-month questionnaires. Improvement in PHQ-9 was observed for patients in both study arms at three months compared to baseline but there was no significant difference in change between Intervention and Control. A significant improvement on FOP-Q-SF scores was seen in the Intervention arm, whereas for those in the Control arm FOP-Q-SF scores deteriorated at 3 months (intervention effect = -4.4 (-7.57, -1.22), p-value = 0.008). CONCLUSIONS: CBT-based psychological support provided after chemotherapy did not significantly alter the spontaneously improving trajectory of depression scores at three months but caused a significant improvement in FOP. Our findings call for the routine implementation of FOP support for ovarian cancer patients.

Benefits and risks of adjuvant treatment with zoledronic acid in stage II/III breast cancer. 10 years follow-up of the AZURE randomized clinical trial (BIG 01/04).

Adjuvant bisphosphonates improve disease outcomes in postmenopausal early breast cancer (EBC) but the long-term effects are poorly described. The AZURE trial (ISRCTN79831382) was designed to determine whether adjuvant zoledronic acid (ZOL) improves disease outcomes in EBC. Previous analyses showed no effect on overall outcomes but identified benefits in postmenopausal women. Here we present the long-term risks and benefits of adjuvant ZOL with 10-years follow-up. PATIENTS AND METHODS: 3360 patients with stage II/III breast cancer were included in an academic, international, phase III, randomized, open label trial. Patients were followed up on a regular schedule until 10 years. Patients were randomized on a 1:1 basis to standard adjuvant systemic therapy +/- intravenous ZOL 4 mg every 3-4 weeks x6, and then at reduced frequency to complete 5 years treatment. The primary outcome was disease free survival (DFS). Secondary outcomes included invasive DFS (IDFS), overall survival (OS), sites of recurrence, skeletal morbidity and treatment outcomes according to primary tumor amplification of the transcription factor, MAF. Pre-planned subgroup analyses focused on interactions between menopausal status and treatment effects. RESULTS: With a median follow up of 117 months [IQR 70.4-120.4), DFS and IDFS were similar in both arms (HRDFS  = 0.94, 95%CI = 0.84-1.06, p = 0.340; HRIDFS  = 0.91, 95%CI = 0.82-1.02, p = 0.116). However, outcomes remain improved with ZOL in postmenopausal women (HRDFS  = 0.82, 95%CI = 0.67-1.00; HRIDFS  = 0.78, 95%CI = 0.64-0.94). In the 79% of tested women with a MAF FISH negative tumor, ZOL improved IDFS (HRIDFS  = 0.75, 95%CI = 0.58-0.97) and OS HROS  = 0.69, 95%CI = 0.50-0.94), irrespective of menopause. ZOL did not improve disease outcomes in MAF FISH + tumors. Bone metastases as a first DFS recurrence (BDFS) were reduced with ZOL (HRB-DFS  = 0.76, 95%CI = 0.63-0.92, p = 0.005). ZOL reduced skeletal morbidity with fewer fractures and skeletal events after disease recurrence. 30 cases of osteonecrosis of the jaw in the ZOL arm (1.8%) have occurred. CONCLUSIONS: Disease benefits with adjuvant ZOL in postmenopausal early breast cancer persist at 10 years of follow-up. The biomarker MAF identified a patient subgroup that derived benefit from ZOL irrespective of menopausal status.

Management of advanced ovarian cancer in South West Wales - a comparison between primary debulking surgery and primary chemotherapy treatment strategies in an unselected, consecutive patient cohort.

OBJECTIVES: This study represents the first reported outcomes for patients with advanced ovarian cancer (AOC) in South-West Wales undergoing treatment with primary debulking surgery or primary chemotherapy respectively. METHODS: This is a retrospective study of consecutive, unselected patients with advanced ovarian, fallopian tube or primary peritoneal cancer (FIGO III/IV) presenting to a regional cancer centre between October 2007 and October 2014. Patients were identified from Welsh Cancer Services records and relevant data was extracted from electronic National Health Service (NHS) databases. Main outcome measures were median overall survival (OS), progression free survival (PFS) and perioperative adverse events. Hazard ratio estimation was carried out with Cox Regression analysis and survival determined by Kaplan-Meier plots. RESULTS: Of 220 women with AOC, 32.3% underwent primary debulking surgery (PDS) and 67.7% primary chemotherapy and interval debulking (PCT-IDS). Patients were often elderly (median age 67 years) with a poor performance status (26.5% PS >1). Complete cytoreduction (0cm residual) was achieved in 32.4% of patients in the PDS group and in 50.0% of patients undergoing IDS. Median OS for all patients was 21.9 months (PDS: 27.0 and PCT-IDS: 19.2 months; p >0.05) and median PFS was 13.1 months (PDS: 14.3 months and PCT-IDS: 13.0 months; p >0.05). Median overall and progression free survival for patients achieving complete cytoreduction were 48.0 and 23.2 months respectively in the PDS group and 35.4 months and 18.6 months in the IDS group (p >0.05). CONCLUSION: This retrospective study of an unselected, consecutive cohort of women with AOC in South West Wales shows comparable survival outcomes with recently published trials, despite the relatively advanced age and poor performance status of our patient cohort. Over the seven-year study period, our data also demonstrated a non-significant trend towards improved survival following primary surgery in patients who achieved maximal cytoreduction. Our future aim therefore is to examine and develop the role of extended surgery in these patients.

GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial.

BACKGROUND: Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women's health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI. PATIENTS AND METHODS: This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI. RESULTS: A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups. CONCLUSION: This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.

MRONJ risk reduction pathway - 360 degree survey.

Introduction Bisphosphonates and denosumab reduce the risk of skeletal events in some malignancies (for example, breast, myeloma). These drugs carry a significant risk of a difficult-to-manage side effect of medication related osteonecrosis of the jaw (MRONJ). Preventive dental screening and treatment reduces the incidence of MRONJ. A managed clinical network (MCN) has been used to provide a MRONJ risk reduction pathway. A 360 degree survey was undertaken to assess the effectiveness of the pathway.Aim The aim of the 360 degree survey was to evaluate if this preventive pathway fulfilled its aims based on patient and stakeholder responses.Method A multidisciplinary, cross-service, cross-health board MRONJ preventive pathway has been developed. A 360 degree feedback survey of patients and other stakeholders was undertaken.Results Overall, this survey revealed high levels of satisfaction across patients, oncologists, community dental services, general dental services, and hospital managers.Conclusion Alternative ways of delivering MRONJ preventive pathways can be developed and assessed using iterative stakeholder feedback aided by a robust clinical governance framework.

Simplified staging laparotomy in FIGO stage 1 epithelial ovarian cancer: follow-up and outcomes in south Wales, U.K.

We have conducted a retrospective analysis of FIGO stage 1 ovarian cancer patients in south Wales, who underwent a simplified staging laparotomy without routine nodal sampling and peritoneal biopsies. Patient records from January 2004 to December 2010 were analysed. A total of 116 patients were included in the final analysis. Adjuvant chemotherapy was offered to patients with risk factors for relapse (grade > 1, clear cell histology, or stage > Ia); overall, 89 patients (76.7%) received adjuvant single agent carboplatin (n = 54, 46.5%) or combination chemotherapy (n = 35, 30.2%). After a median follow up of 41 months (range 12-95), 18 patients have relapsed (15.5%), of these 17 had risk factors and 16 had received adjuvant chemotherapy. Eighteen patients have died, of whom 6 of non-cancer related causes without prior relapse. 5-year overall and relapse free survival were 80%. In conclusion, in situations where there are limited resources and operating time constraints, our data suggest that a simplified staging laparotomy approach may be a reasonable compromise in apparently early stage ovarian cancer: this may result in a more aggressive use of chemotherapy, but survival outcomes seem comparable to other series.

A comparison of measured and estimated glomerular filtration rate for carboplatin dose calculation in stage I testicular seminoma.

UNLABELLED: Dose calculation of adjuvant carboplatin chemotherapy for stage I testicular seminoma, based on area under the concentration curve (AUC), incorporates the glomerular filtration rate (GFR). This retrospective study compares 'gold standard' (51)Cr-ethylenediamine tetraacetic acid ((51)Cr-EDTA) GFR measurements with renal function estimations derived from the Cockcroft-Gault, Jelliffe and Wright formulae. INCLUSION CRITERIA: stage I testicular seminoma treated with a single dose of carboplatin AUC7 at one centre in South Wales, UK, between 2005 and 2011, with contemporaneous (51)Cr-EDTA GFR measurement and serum creatinine. Renal function estimates obtained using Cockcroft-Gault, Jelliffe and Wright formulae were analysed for bias (mean percentage error, MPE) and precision (mean absolute percentage error, MAPE) compared to the gold standard. Sixty-eight patients were identified, median age 40 (range 17-66), median creatinine 82 (range 55-120). For the Cockcroft-Gault, Jelliffe and Wright formulae, respectively, MPE was +12.4, -32.3 and +8.8; MAPE was 16.0, 32.7 and 12.9; and substitution of the calculated GFR result for (51)Cr-EDTA measurement would have resulted in a >10% discrepancy in carboplatin dose in 41.1, 97.1 and 42.6% of patients (predominantly overdoses for the Cockcroft-Gault and Wright formulae, underdoses for the Jelliffe formula). Of the formulae analysed, none accurately correlated with (51)Cr-EDTA GFR measurements.

A decision impact, decision conflict and economic assessment of routine Oncotype DX testing of 146 women with node-negative or pNImi, ER-positive breast cancer in the U.K.

BACKGROUND: Tumour gene expression analysis is useful in predicting adjuvant chemotherapy benefit in early breast cancer patients. This study aims to examine the implications of routine Oncotype DX testing in the U.K. METHODS: Women with oestrogen receptor positive (ER+), pNO or pN1mi breast cancer were assessed for adjuvant chemotherapy and subsequently offered Oncotype DX testing, with changes in chemotherapy decisions recorded. A subset of patients completed questionnaires about their uncertainties regarding chemotherapy decisions pre- and post-testing. All patients were asked to complete a diary of medical interactions over the next 6 months, from which economic data were extracted to model the cost-effectiveness of testing. RESULTS: Oncotype DX testing resulted in changes in chemotherapy decisions in 38 of 142 (26.8%) women, with 26 of 57 (45.6%) spared chemotherapy and 12 of 85 (14.1%) requiring chemotherapy when not initially recommended (9.9% reduction overall). Decision conflict analysis showed that Oncotype DX testing increased patients' confidence in treatment decision making. Economic analysis showed that routine Oncotype DX testing costs £6232 per quality-adjusted life year gained. CONCLUSION: Oncotype DX decreased chemotherapy use and increased confidence in treatment decision making in patients with ER+ early-stage breast cancer. Based on these findings, Oncotype DX is cost-effective in the UK setting.

UK guidance document: treatment of metastatic breast cancer.

Although there have been major improvements in the management of breast cancer, with a rapidly falling death rate despite an increasing incidence of the disease, metastatic breast cancer remains common and the cause of death in nearly 12 000 women annually in the UK. Numerous treatment options are available that either target the tumour or reduce the complications of the disease. Clinical decision making depends on knowledge of the extent and biology of the disease and available drug options, an understanding of the functional status, and also the wishes and expectations of the individual patient. In addition, the organisation of services and support of the patient are essential components of high-quality care. The National Institute for Health and Clinical Excellence (NICE) has produced guidelines for the treatment of advanced breast cancer, which in some areas have perhaps failed to appreciate the complexity of patient management. This guidance document aims to provide succinct practical advice on the treatment of metastatic breast cancer, highlight some limitations of the NICE guidelines, and provide suggestions for management where available data are limited.

Long-term endometrial effects in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES)--a randomised controlled trial of exemestane versus continued tamoxifen after 2-3 years tamoxifen.

BACKGROUND: The antiestrogen tamoxifen may have partial estrogen-like effects on the postmenopausal uterus. Aromatase inhibitors (AIs) are increasingly used after initial tamoxifen in the adjuvant treatment of postmenopausal early breast cancer due to their mechanism of action: a potential benefit being a reduction of uterine abnormalities caused by tamoxifen. PATIENTS AND METHODS: Sonographic uterine effects of the steroidal AI exemestane were studied in 219 women participating in the Intergroup Exemestane Study: a large trial in postmenopausal women with estrogen receptor-positive (or unknown) early breast cancer, disease free after 2-3 years of tamoxifen, randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years adjuvant treatment. The primary end point was the proportion of patients with abnormal (> or =5 mm) endometrial thickness (ET) on transvaginal ultrasound 24 months after randomisation. RESULTS: The analysis included 183 patients. Two years after randomisation, the proportion of patients with abnormal ET was significantly lower in the exemestane compared with tamoxifen arm (36% versus 62%, respectively; P = 0.004). This difference emerged within 6 months of switching treatment (43.5% versus 65.2%, respectively; P = 0.01) and disappeared within 12 months of treatment completion (30.8% versus 34.7%, respectively; P = 0.67). CONCLUSION: Switching from tamoxifen to exemestane significantly reverses endometrial thickening associated with continued tamoxifen.

The process of truth disclosure: an assessment of the results of information during the diagnostic phase in patients with cancer.

BACKGROUND: Surveys carried out in Mediterranean countries demonstrated very low rates of awareness of both diagnosis and prognosis among cancer patients. In our institution, a long-term training program aimed at improving communication skills among all physicians interacting with cancer patients was conducted. We report here the results of an extensive assessment of patients' awareness conducted after the first training period. PATIENTS AND METHODS: In a 2-year period, after every first visit of patients with a histological diagnosis of cancer, oncologists elicited perception of the patients and completed a structured questionnaire focusing on the understanding of the diagnosis and prognosis. Our data are thus a photograph of the results of the informative process conducted during the diagnostic phase. RESULTS: Among the enrolled 649 patients, 79.3% were aware of their diagnosis; factors significantly associated with higher levels of awareness were age younger than 70 and referral from surgery (versus internal medicine). Knowledge about the palliative or curative aims of future treatments (a surrogate sign of prognostic consciousness) was evident in 55.2%. CONCLUSIONS: Compared with historical data, our results show a high level of comprehension of the diagnosis of malignancy, probably due to the extensive training effort together with the method chosen for assessment.

Indicadores biológicos para la valoración de la exposición humana a compuestos químicos industriales : Mercurio

Traducción de la obra en inglés \"Biological indicators for the assessment of human exposure to industrial chemicals\" (EUR 10704 EN) publicada por la Oficina para las Publicaciones Oficiales de las Comunidades Europeas. Contiene: propiedades químicas y físicas del mercurio, efectos en los humanos, mutagesis, metabolismo, control biológico...

Indicadores biológicos para la valoración de la exposición humana a compuestos químicos industriales : Acrilonitrilo

Traducción de la obra en inglés \"Biological indicators for the assessment of human exposure to industrial chemicals\" (EUR 8903 EN) publicada por la Oficina para las Publicaciones Oficiales de las Comunidades Europeas. Contiene: propiedades químicas y físicas del acrilonitrilo, efectos en los humanos, metabolismo, indicadores biológicos, indicadores de efectos...

Indicadores biológicos para la valoración de la exposición humana a compuestos químicos industriales : Cinc

Traducción de la obra en inglés \"Biological indicators for the assessment of human exposure to industrial chemicals\" (EUR 8903 EN) publicada por la Oficina para las Publicaciones Oficiales de las Comunidades Europeas. Contiene: propiedades químicas y físicas del cinc, efectos en los humanos, metabolismo, indicadores biológicos...

Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.

BACKGROUND: Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival. METHODS: 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920. RESULTS: After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded. CONCLUSIONS: Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.