Multicentre study of surgical referral and outcomes of patients with benign colorectal lesions.

Background: A multicentre cohort study was performed to analyse the motivations for surgical referral of patients with benign colorectal lesions, and to evaluate the endoscopic and pathological characteristics of these lesions as well as short-term surgical outcomes. Methods: Patients who underwent surgery for a benign colorectal lesion in 15 Dutch hospitals between January 2014 and December 2017 were selected from the pathology registry. Lesions were defined as complex when at least one of the following features was present: size at least 40 mm, difficult location according to the endoscopist, previous failed attempt at resection, or non-lifting sign. Results: A total of 358 patients were included (322 colonic and 36 rectal lesions). The main reasons for surgical referral of lesions in the colon and rectum were large size (33·5 and 47 per cent respectively) and suspicion of invasive growth (31·1 and 58 per cent). Benign lesions could be categorized as complex in 80·6 per cent for colonic and 80 per cent for rectal locations. Surgery consisted of local excision in 5·9 and 64 per cent of colonic and rectal lesions respectively, and complicated postoperative course rates were noted in 11·2 and 3 per cent. In the majority of patients, no attempt was made to resect the lesion endoscopically (77·0 per cent of colonic and 83 per cent of rectal lesions). Conclusion: The vast majority of the benign lesions referred for surgical resection could be classified as complex. Considering the substantial morbidity of surgery for benign colonic lesions, reassessment for endoscopic resection by another advanced endoscopy centre seems to be underused and should be encouraged.

Antecedentes: Se realizó un estudio de cohorte multicéntrico para analizar los motivos de la derivación quirúrgica de pacientes con lesiones colorrectales benignas y evaluar las características endoscópicas y patológicas de estas lesiones, así como los resultados quirúrgicos a corto plazo. Métodos: A partir de un registro anatomopatológico, se seleccionaron los pacientes que se sometieron a cirugía por una lesión colorrectal benigna en 15 hospitales holandeses entre enero de 2014 y diciembre de 2017. Se definió como lesión compleja aquella que presentaba, al menos, una de las siguientes características: tamaño > 40 mm, ubicación difícil según el endoscopista, fracaso previo de la resección o signo de no­elevación. Resultados: Se incluyeron 358 pacientes (322 lesiones de colon y 36 rectales). Las principales razones para la derivación quirúrgica de las lesiones de colon y recto fueron el gran tamaño (34% y 47%) y la sospecha de crecimiento invasivo (31% y 58%). Las lesiones benignas se consideraron complejas en el 81% de los casos del colon y en el 80% del recto. La cirugía consistió en una exéresis local en el 6% y el 64% y se observó una tasa de complicaciones postoperatorias del 11% y el 3% de las lesiones de colon y recto, respectivamente. En la mayoría de los casos, no se intentó la resección endoscópica de la lesión (77% en colon y 83% en recto). Conclusión: La gran mayoría de las lesiones benignas derivadas para la resección quirúrgica podrían clasificarse como complejas. Considerando la notable morbilidad de la cirugía de las lesiones benignas de colon, debería contemplarse y fomentarse la reevaluación de la resección endoscópica en un centro de endoscopia avanzada.

National cohort study on postoperative risks after surgery for submucosal invasive colorectal cancer.

Background: The decision to perform surgery for patients with T1 colorectal cancer hinges on the estimated risk of lymph node metastasis, residual tumour and risks of surgery. The aim of this observational study was to compare surgical outcomes for T1 colorectal cancer with those for more advanced colorectal cancer. Methods: This was a population-based cohort study of patients treated surgically for pT1-3 colorectal cancer between 2009 and 2016, using data from the Dutch ColoRectal Audit. Postoperative complications (overall, surgical, severe complications and mortality) were compared using multivariable logistic regression. A risk stratification table was developed based on factors independently associated with severe complications (reintervention and/or mortality) after elective surgery. Results: Of 39 813 patients, 5170 had pT1 colorectal cancer. No statistically significant differences were observed between patients with pT1 and pT2-3 disease in the rate of severe complications (8·3 versus 9·5 per cent respectively; odds ratio (OR) 0·89, 95 per cent c.i. 0·80 to 1·01, P = 0·061), surgical complications (12·6 versus 13·5 per cent; OR 0·93, 0·84 to 1·02, P = 0·119) or mortality (1·7 versus 2·5 per cent; OR 0·94, 0·74 to 1·19, P = 0·604). Male sex, higher ASA grade, previous abdominal surgery, open approach and type of procedure were associated with a higher severe complication rate in patients with pT1 colorectal cancer. Conclusion: Elective bowel resection was associated with similar morbidity and mortality rates in patients with pT1 and those with pT2-3 colorectal carcinoma.

Introduction of a colorectal cancer screening programme: results from a single-centre study.

AIM: In 2014, a national colorectal cancer (CRC) screening programme was launched in the Netherlands. It is difficult to assess for the individual patients with CRC whether the oncological benefits of surgery will outweigh the morbidity of the procedure, especially in early lesions. This study compares patient and tumour characteristics between screen-detected and nonscreen-detected patients. Also, we present an overview of treatment options and clinical dilemmas when treating patients with early-stage colorectal disease. METHOD: Between January 2014 and December 2016, all patients with nonmalignant polyps or CRC who were referred to the Department of Surgery of the Leiden University Medical Centre in the Netherlands were included. Baseline characteristics, type of treatment and short-term outcomes of patients with screen-detected and nonscreen-detected colorectal tumours were compared. RESULTS: A total of 426 patients were included, of whom 240 (56.3%) were identified by screening. Nonscreen-detected patients more often had comorbidity (P = 0.03), the primary tumour was more often located in the rectum (P = 0.001) and there was a higher rate of metastatic disease (P < 0.001). Of 354 surgically treated patients, postoperative adverse events did not significantly differ between the two groups (P = 0.38). Of 46 patients with T1 CRC in the endoscopic resection specimen, 23 underwent surgical resection of whom only 30.4% had residual invasive disease at colectomy. CONCLUSION: Despite differences in comorbidity, stage and surgical outcome of patients with screen-detected tumours compared to nonscreen-detected tumours were not significantly different. Considering its limited oncological benefits as well as the rate of adverse events, surgery for nonmalignant polyps and T1 CRC should be considered carefully.

Colorectal cancer screening: Systematic review of screen-related morbidity and mortality.

BACKGROUND: Implementation of mass colorectal cancer screening, using faecal occult blood test or colonoscopy, is recommended by the European Union in order to increase cancer-specific survival by diagnosing disease in an earlier stage. Post-colonoscopy complications have been addressed by previous systematic reviews, but morbidity of colorectal cancer screening on multiple levels has never been evaluated before. AIM: To evaluate potential harm as a result of mass colorectal cancer screening in terms of complications after colonoscopy, morbidity and mortality following surgery, psychological distress and inappropriate use of the screening test. METHODS: A systematic review of all literature on morbidity and mortality attributed to colorectal cancer screening, using faecal occult blood test or colonoscopy, from each databases' inception to August 2016 was performed. A meta-analysis was conducted to examine the pooled incidence of major complications of colonoscopy (major bleedings and perforations). RESULTS: Sixty studies were included. Five out of seven included prospective studies on psychological morbidity reported an association between participation in a colorectal screening program and psychological distress. Serious morbidity from colonoscopy in asymptomatic patients included major bleedings (0.8/1000 procedures, 95% CI 0.18-1.63) and perforations (0.07/1000 procedures, 95% CI 0.006-0.17). CONCLUSIONS: Participation in a colorectal cancer screening program is associated with psychological distress and can cause serious adverse events. Nevertheless, the short duration of psychological impact as well as the low colonoscopy complication rate seems reassuring. Because of limited literature on harms other than perforation and bleeding, future research on this topic is greatly needed to contribute to future screening recommendations.

Drug-induced progressive multifocal leukoencephalopathy: Lessons learned from contrasting natalizumab and rituximab.

Progressive multifocal leukoencephalopathy (PML) has been identified as a serious adverse drug reaction (ADR) of several immunomodulatory biologicals. In this study, we contrasted the reporting patterns of PML for two biologicals for which the risk was identified at different points in their lifecycle: natalizumab (before reapproval) and rituximab (nine years postapproval). We found that, apart from the differences in clinical characteristics (age, gender, indication, time to event, fatality), which reflect the diversity in context of use, PML reports for natalizumab were more complete and were received sooner after occurrence. This study serves as an important reminder that spontaneous reports should only be used with great caution to quantify and compare safety profiles across products over time. The observed variability in reporting patterns and heterogeneity of PML cases presents challenges to such comparisons. Lumping uncharacterized PML reports together without taking these differences into account may result in biased comparisons and flawed conclusions about differential safety.

Strategy in Regulatory Decision-Making for Management of Progressive Multifocal Leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) has been observed after the use of several medicines, including monoclonal antibodies. As these drugs play important roles in the therapeutic armamentarium, it is important to address the challenges that this severe adverse reaction poses to the safe use of medicines. Considering the need for consistent outcomes of regulatory decisions, the European Medicines Agency Pharmacovigilance Risk Assessment Committee (PRAC) used PML as an example to develop a systematic approach to labeling and risk minimization.

Risk management plans as a tool for proactive pharmacovigilance: a cohort study of newly approved drugs in Europe.

Risk Management Plans (RMPs) have become a cornerstone in the pharmacovigilance of new drugs in Europe. The RMP was introduced in 2005 to support a proactive approach in gaining knowledge on safety concerns through early planning of pharmacovigilance activities. However, the rate at which uncertainties in the safety profile are resolved through this proactive approach is unknown. We therefore examined the evolution of safety concerns in the RMP after initial approval for a selected cohort of 48 drugs, to provide insight into the knowledge gain over time. We found that 20.7% of the uncertainties existing at approval had been resolved 5 years after approval. Because new uncertainties were included in the RMP at a similar rate, the overall number of uncertainties remained approximately equal. The relatively modest accrual of knowledge, as demonstrated in this study through resolution of uncertainties, suggests that opportunities for optimization exist while ensuring feasible and risk-proportionate pharmacovigilance planning.

Association of isolated short fetal femur with intrauterine growth restriction.

OBJECTIVES: To analyze the outcomes of fetuses referred because of short femur length. METHODS: This was a retrospective study of all singleton pregnancies referred to a tertiary care referral hospital with a femur length below the 5(th) percentile. All ultrasound scan reports, including Doppler, fetal karyotyping, pregnancy outcome and neonatal data were analyzed. RESULTS: In 112 patients, 87 (78%) had an isolated short femur and 25 (22%) had a non-isolated short femur. The non-isolated cases consisted of chromosomal disorders (n = 6), skeletal abnormalities (n = 6), multiple abnormalities (n = 12) and 1 genetic disorder. In the isolated group 37 cases (43%) were intrauterine growth restricted (positive likelihood ratio 1.20, negative likelihood ratio 0.45). In 33 cases the short femur was unexplained and 17 referrals were considered false-positive. The growth restricted group had significant more abnormal Doppler measurements (p = 0.01), caesarean deliveries (p = 0.043) and admissions to the neonatal intensive care unit (p = 0.001). CONCLUSION: An isolated short femur is associated with intrauterine growth restriction and adverse pregnancy outcome.

Liver transplantation in a patient with an intraabdominally located left ventricular assist device: surgical aspects--case report.

The presence of a cardiac assist device in a liver transplantation candidate should not be considered to be an absolute contraindication to transplantation. In this first case report of liver transplantation in a patient with an intraabdominally located left ventricular assist device, we have described the surgical aspects and discussed the timing of the liver transplantation and the removal of the left ventricular assist device.

Utilization of evidence-based therapy for the secondary prevention of acute coronary syndromes in Australian practice.

AIM: To review and document the current utilization of pharmacotherapy for the secondary prevention of acute coronary syndromes (ACS) in patients discharged from an Australian hospital. METHODS: A retrospective cross-sectional study was conducted at a major Sydney teaching hospital. Patients with either a primary or secondary diagnosis of acute coronary syndrome were identified from medical records over a 4-month period (January-April 2007). A range of clinical data was extracted from medical records, including medical history, clinical presentation and pharmacotherapy both on admission and at discharge. This audit focussed on the use of four guideline-recommended therapies: aspirin +/- clopidogrel, beta blockers, statins and ACE-inhibitors (ACE-I), as well as the utilization of multiple antithrombotics. RESULTS: Data pertaining to a total of 169 patients was extracted and reviewed. The mean age of the study population was 65.9 years and 71% of the population was male. Non-ST-segment elevation myocardial infarction (Non-STEMI) accounted for 42% of the admissions, whereas 33.7% and 24.3% of the patients were respectively admitted for ST-segment elevation myocardial infarction (STEMI) or unstable angina. After accounting for reported contra-indications, overall, 96% of the eligible patients received antithrombotics comprising of at least aspirin, and 79% of eligible patients received aspirin plus clopidogrel. Furthermore, 82% of eligible patients received a beta-blocker at discharge, 86% a statin and 79% received either an ACE-I or angiotensin-II receptor antagonist. Compared with patients who presented with myocardial infarction (with or without ST-segment elevation), those presenting with unstable angina were less likely to receive a beta-blocker (OR = 0.19, 95%-CI: 0.08-0.48) or an ACE-agent (OR = 0.15, 95%-CI: 0.06-0.39) at discharge. Patients over 65 years of age were also less likely to receive a beta-blocker (OR = 0.35, 95%-CI: 0.14-0.89) or an ACE-agent (OR = 0.28 95%-CI: 0.11-0.70) at discharge, but were also less likely to receive the combination of aspirin plus clopidogrel (OR = 0.19, 95%-CI: 0.07-0.54) at discharge, compared with younger patients. Men were more likely to be discharged on a statin (OR = 3.36, 95%-CI: 1.11-10.15), compared with women. Only six patients (4%) received three or more antithrombotics at discharge; five of these received the triple combination of aspirin, clopidogrel and warfarin. CONCLUSIONS: There is a good adherence to evidence-based guidelines for the secondary prevention of ACS in this local setting. However, there is some potential underutilization in the older population and patients presenting with unstable angina. Variability in the use of oral anticoagulants alongside dual antiplatelet therapy indicates there is potentially a need for further guidance regarding the prescription of antithrombotics in those requiring poly-therapy.