National differences in implementation of minimally invasive surgery for colorectal cancer and the influence on short-term outcomes.

BACKGROUND: The timing and degree of implementation of minimally invasive surgery (MIS) for colorectal cancer vary among countries. Insights in national differences regarding implementation of new surgical techniques and the effect on postoperative outcomes are important for quality assurance, can show potential areas for country-specific improvement, and might be illustrative and supportive for similar implementation programs in other countries. Therefore, this study aimed to evaluate differences in patient selection, applied techniques, and results of minimal invasive surgery for colorectal cancer between the Netherlands and Sweden. METHODS: Patients who underwent elective minimally invasive surgery for T1-3 colon or rectal cancer (2012-2018) registered in the Dutch ColoRectal Audit or Swedish ColoRectal Cancer Registry were included. Time trends in the application of MIS were determined. Outcomes were compared for time periods with a similar level of MIS implementation (Netherlands 2012-2013 versus Sweden 2017-2018). Multilevel analyses were performed to identify factors associated with adverse short-term outcomes. RESULTS: A total of 46,095 Dutch and 8,819 Swedish patients undergoing MIS for colorectal cancer were included. In Sweden, MIS implementation was approximately 5 years later than in the Netherlands, with more robotic surgery and lower volumes per hospital. Although conversion rates were higher in Sweden, oncological and surgical outcomes were comparable. MIS in the Netherlands for the years 2012-2013 resulted in a higher reoperation rate for colon cancer and a higher readmission rate but lower non-surgical complication rates for rectal cancer if compared with MIS in Sweden during 2017-2018. CONCLUSION: This study showed that the implementation of MIS for colorectal cancer occurred later in Sweden than the Netherlands, with comparable outcomes despite lower volumes. Our study demonstrates that new surgical techniques can be implemented at a national level in a controlled and safe way, with thorough quality assurance.

International evaluation of circumferential resection margins after rectal cancer resection: insights from the Swedish and Dutch audits.

AIM: This study aimed to determine predictive factors for the circumferential resection margin (CRM) within two northern European countries with supposed similarity in providing rectal cancer care. METHOD: Data for all patients undergoing rectal resection for clinical tumour node metastasis (TNM) stage I-III rectal cancer were extracted from the Swedish ColoRectal Cancer Registry and the Dutch ColoRectal Audit (2011-2015). Separate analyses were performed for cT1-3 and cT4 stage. Predictive factors for the CRM were determined using univariable and multivariable logistic regression analyses. RESULTS: A total of 6444 Swedish and 12 089 Dutch patients were analysed. Over time the number of hospitals treating rectal cancer decreased from 52 to 42 in Sweden, and 82 to 79 in the Netherlands. In the Swedish population, proportions of cT4 stage (17% vs 8%), multivisceral resection (14% vs 7%) and abdominoperineal excision (APR) (37% vs 31%) were higher. The overall proportion of patients with a positive CRM (CRM+) was 7.8% in Sweden and 5.4% in the Netherlands. In both populations with cT1-3 stage disease, common independent risk factors for CRM+ were cT3, APR and multivisceral resection. No common risk factors for CRM+ in cT4 stage disease were found. An independent impact of hospital volume on CRM+ could be demonstrated for the cT1-3 Dutch population. CONCLUSION: Within two northern European countries with implemented clinical auditing, rectal cancer care might potentially be improved by further optimizing the treatment of distal and locally advanced rectal cancer.

Redo coloanal anastomosis for anastomotic leakage after low anterior resection for rectal cancer: an analysis of 59 cases.

AIM: The construction of a new coloanal anastomosis (CAA) following anastomotic leakage after low anterior resection (LAR) is challenging. The available literature on this topic is scarce. The aim of this two-centre study was to determine the clinical success and morbidity after redo CAA. METHOD: This retrospective cohort study included all patients with anastomotic leakage after LAR for rectal cancer who underwent a redo CAA between 2010 and 2014 in two tertiary referral centres. Short- and long-term morbidity were analysed, including both anastomotic leakage and permanent stoma rates on completion of follow-up. RESULTS: A total of 59 patients were included, of whom 45 (76%) were men, with a mean age of 59 years (SD ± 9.4). The median interval between index and redo surgery was 14 months [interquartile range (IQR) 8-27]. The median duration of follow-up was 27 months (IQR 17-36). The most frequent complication was anastomotic leakage of the redo CAA occurring in 24 patients (41%), resulting in a median of three reinterventions (IQR 2-4) per patient. At the end of follow-up, bowel continuity was restored in 39/59 (66%) patients. Fourteen (24%) patients received a definitive colostomy and six (10%) still had a diverting ileostomy. In a multivariable model, leakage of the redo CAA was the only risk factor for permanent stoma (OR 0.022; 95% CI 0.004-0.122). CONCLUSION: Redo CAA is a viable option in selected patients with persisting leakage after LAR for rectal cancer who want their bowel continuity restored. However, patients should be fully informed about the relatively high morbidity and reintervention rates.

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer.

BACKGROUND: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. METHODS/STUDY DESIGN: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. DISCUSSION: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. TRIAL REGISTRATION: NCT02371304 , registration date: February 2015.

Clinical effects of an optimised care program with telehealth in heart failure patients in a community hospital in the Netherlands.

BACKGROUND: Our hypothesis was that telehealth in combination with an optimised care program coordinated amongst care professionals in primary, secondary and tertiary care can achieve beneficial outcomes in heart failure. The objective was to evaluate the clinical effects of introduction of telehealth in an optimised care program in a community hospital in the north of the Netherlands. METHODS: We compared the number of unplanned admissions for heart failure in the year before and after adding telehealth to the optimised care program. Furthermore, blood pressure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were evaluated at baseline and 3, 6 and 12 months after telehealth. Quality of life and knowledge about the disease were regularly evaluated via surveys on the telehealth system. FINDINGS: The number of unplanned admissions for heart failure decreased from on average 1.29 to 0.31 admissions per year after telehealth introduction. Blood pressure decreased independent of medication and NT-proBNP levels improved as well. Quality of life increased during the telehealth intervention and disease knowledge remained high throughout the follow-up period. Unplanned admissions that remained after telehealth introduction could be accurately predicted at baseline by a multivariate regression model.

Registering the critical view of safety: photo or video?

BACKGROUND: One of the most important ways to reduce biliary duct injury in laparoscopic cholecystectomy is to achieve the critical view of safety (CVS) before transection of the cystic artery and duct. Documenting CVS is possible with photo prints, video imaging, or both. These documentations can be used as a proof of the right procedure in case of biliary duct injury, but only if the documentation is good enough to be judged independently by others. METHODS: In 102 consecutive laparoscopic cholecystectomies, CVS was recorded by photo prints and video images. Imaging was done just before transection of the cystic artery and duct. The photo prints and video images were analyzed independently by two surgeons. These surgeons had to judge whether the documentation method was of sufficient quality to determine whether CVS was achieved. RESULTS: Photo prints were made for 81% and video images for 59% of the 102 patients treated with a laparoscopic cholecystectomy. The mean age of the patients was 54 years (range, 22-83 years), and 71% were women. The diagnosis for 62 of the patients was symptomatic cholecystolithiasis, and 18 patients had acute cholecystitis. The remaining patients had earlier experienced acute cholecystitis, biliary pancreatitis, or endoscopic retrograde cholangiopancreatography (ERCP). Respectively, 30% and 21% of the CVS photo prints were judged to be of insufficient quality to determine whether CVS had been established, mostly because of difficulties adequately showing the lateral side (κ = 0.67). In all but two video images, achievement of CVS was documented sufficiently to be judged 97% (κ = 1.00). CONCLUSION: Photo prints are inferior to video images for judging achievement of CVS. Therefore, a practical and logistical solution must be devised in hospitals for storage and insight in all video documentation, for example, by implementation of a link with the electronic patient database.

[The value of positron emission tomography in the diagnosis and treatment of oesophageal cancer]. / De waarde van positronemissietomografie bij de diagnostiek en behandeling van het oesofaguscarcinoom.

Fludeoxyglucose positron emission tomography (FDG-PET) is a noninvasive imaging technique that applies the glucose metabolism to visualise the metabolic activity ofa tumour. FDG-PET might improve the selection of potentially curable patients with oesophageal cancer in addition to state-of-the-art conventional work-up (e.g. endoscopic ultrasonography and spiral CT). The additional value however is only 4% for all patients, and 7% in patients with stage III-IV disease. Moreover, the additional costs of FDG-PET are not compensated by the cost reduction ofprevented surgery. To improve the outcome of patients with oesophageal cancer the value ofneoadjuvant chemo- and/or radiotherapy is being investigated. FDG-PET seems to be a promising tool for the early assessment of response to neoadjuvant therapy. In case of non-response the ineffective neoadjuvant therapy can be stopped without further delaying appropriate surgery. FDG-PET might be able to improve the prediction of prognosis, in addition to commonly used histopathological factors.

Limited additional value of positron emission tomography in staging oesophageal cancer.

BACKGROUND: The detection of distant metastases in patients with oesophageal cancer may be improved with [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), preventing unnecessary surgical explorations. The aim of this study was to assess the additional value of FDG-PET after a state-of-the-art preoperative staging protocol. METHODS: All patients in this prospective cohort study were staged with multidetector computed tomography, endoscopic ultrasonography and external ultrasonography of the neck, both combined with selective fine-needle aspiration cytology. Patients considered eligible for curative surgery after these investigations underwent FDG-PET. RESULTS: FDG-PET revealed suspicious hot spots in 30 (15.1 per cent) of 199 patients. Metastases were confirmed in eight (4.0 per cent). In six of these, distant metastases were confirmed before surgery, but exploratory surgery was necessary for histological confirmation in the other two. All eight upstaged patients had clinical stage III-IV disease before FDG-PET (6.6 per cent of 122 with stage III-IV disease). In seven patients (3.5 per cent) hot spots appeared to be synchronous neoplasms, mainly colonic polyps. However, those in the remaining 15 (7.5 per cent) were false positive, leading to unnecessary additional investigations. CONCLUSION: FDG-PET improves the selection of patients with oesophageal cancer for potentially curative surgery, especially in stages III-IV. However, the diagnostic benefit is limited after state-of-the-art staging, and so broad implementation in daily clinical practice is questionable.

Effects of clarithromycin, azithromycin and rifampicin on terbutaline-induced sweating in foals.

BACKGROUND: Erythromycin (ERY) induces anhidrosis in foals. Azithromycin (AZI) and clarithromycin (CLA), often combined with rifampicin (RIF), are commonly used to treat Rhodococcus equi infections, but effects on sweating have not been investigated. OBJECTIVE: To determine the effects of AZI, CLA and RIF on sweat responses in normal foals. STUDY DESIGN: Each experiment was a blinded, duplicated, six foal × three period counterbalanced within subjects design (12 foals/experiment). METHODS: Antimicrobials were given orally for 5 days. In Experiment 1, ERY, AZI and CLA were given. In Experiment 2, ERY, RIF and ERY/RIF combination were used. Quantitative intradermal terbutaline sweat tests were performed daily for 3 days before and 1, 2, 5, 9, 24, and 39 days after treatment. Data were analysed by repeated measures analysis of variance procedures. Significance was P≤0.05. RESULTS: In Experiment 1, all macrolides suppressed sweating although CLA and AZI were less potent than ERY. In Experiment 2, significant sweat suppression occurred in foals given ERY with or without RIF, but there was no effect of RIF alone. Rifampicin reduced sweat suppression by ERY on Day 1 of treatment but not thereafter. MAIN LIMITATIONS: Because ERY blood concentrations were not measured, effects of RIF on ERY-induced anhidrosis could not definitively be ascribed to altered ERY bioavailability. CONCLUSIONS: All macrolides commonly used to treat R. equi pneumonia, i.e. ERY, AZI and CLA, induce anhidrosis in foals. The potent anti-sudorific effect of ERY is delayed, but not substantially affected by concurrent RIF administration.

Systematic review of the staging performance of 18F-fluorodeoxyglucose positron emission tomography in esophageal cancer.

PURPOSE: Despite the increasing number of publications concerning (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) for staging of esophageal cancer and the increasing availability of this novel diagnostic modality, its exact role in preoperative staging of these tumors is still unknown. The aim of this study was to systematically review the literature regarding the diagnostic performance of FDG-PET in preoperative staging of patients with esophageal cancer, and to calculate summary estimates of its sensitivity and specificity. METHODS: The databases of PubMed, Embase, and Cochrane were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. A meta-analysis of the reported sensitivity and specificity of each study was performed. RESULTS: Twelve studies met the inclusion criteria. The studies had several design deficiencies. Pooled sensitivity and specificity for the detection of locoregional metastases were 0.51 (95% CI, 0.34 to 0.69) and 0.84 (95% CI, 0.76 to 0.91), respectively. For distant metastases, pooled sensitivity and specificity were 0.67 (95% CI, 0.58 to 0.76) and 0.97 (95% CI, 0.90 to 1.0), respectively. CONCLUSION: FDG-PET showed moderate sensitivity and specificity for the detection of locoregional metastases, and reasonable sensitivity and specificity in detection of distant lymphatic and hematogenous metastases.

A "crackleware" oesophagus.

This case report describes a 70 year old woman with excessive diffuse keratinisation of the oral cavity and oesophagus harbouring a squamous cell carcinoma. This excessive diffuse keratinisation of normally non-keratinised squamous epithelium could not be identified in normally non-keratinised epithelia in other parts of the body (the vagina), arguing against a genetic basis for this disorder. The term "crackleware" oesophagus was used to describe this entity, which has not been described previously in the English literature.

Endocrine and metabolic responses in children with meningoccocal sepsis: striking differences between survivors and nonsurvivors.

To get insight in the endocrine and metabolic responses in children with meningococcal sepsis 26 children were studied the first 48 h after admission. On admission there was a significant difference in cortisol/ACTH levels between nonsurvivors (n = 8) and survivors (n = 18). Nonsurvivors showed an inadequate cortisol stress response in combination to very high ACTH levels, whereas survivors showed a normal stress response with significantly higher cortisol levels (0.62 vs. 0.89 micromol/L) in combination with moderately increased ACTH levels (1234 vs. 231 ng/L). Furthermore, there was a significant difference between nonsurvivors and survivors regarding pediatric risk of mortality score (31 vs. 17), TSH (0.97 vs. 0.29 mE/L), T3 (0.53 vs. 0.38 nmol/L), reverse T3 (rT3) (0.75 vs. 1.44 nmol/L), C-reactive protein (34 vs. 78 mg/L), nonesterified fatty acids (0.32 vs. 0.95 mmol/L), and lactate (7.3 vs. 3.2 mmol/L). In those who survived, the most important changes within 48 h were seen in a normalization of cortisol and ACTH levels, but without a circadian rhythm; a decrease of rT3 and an increase in the T3/rT3 ratio; and a decrease in the levels of the nonesterified free fatty acids and an unaltered high urinary nitrogen excretion. At this moment, it is yet unknown whether the hormonal abnormalities are determining factors in the outcome of acute meningococcal sepsis or merely represent secondary effects. Understanding the metabolic and endocrine alterations is required to design possible therapeutic approaches. The striking difference between nonsurvivors and survivors calls for reconsideration of corticosteroid treatment in children with meningococcal sepsis.

No additional value of routine check X-rays after internal fixation of hip fractures.

PURPOSE: Annually approximately 18,044 patients are admitted to Dutch hospitals with hip fractures. This is an increasing demand for medical care due to the increasing amount of elderly people. Although previous studies showed that routine check of X-rays following hip fracture surgery is unnecessary, it remains routine in most clinics in the Netherlands. In addition to the radiation exposure to the patient, it is painful and leads to unnecessary costs. This study aims to establish if routine check X-rays 1 day after internal fixation for hip fracture with adequate image intensifier guidance influence postoperative management. PATIENTS AND METHODS: A retrospective study was performed for all patients undergoing internal fixation of hip fractures with image intensifier guidance in the period from January 2006 until December 2007 in our hospital. RESULTS: In that period 294 patients underwent internal fixation of hip fractures, 254 underwent a check X-ray and were included in this study. In only two patients the check X-ray did change patient management. CONCLUSION: A check X-ray following internal fixation of hip fractures after adequate peroperative image intensifier guidance is not useful. Dismissing this unuseful medical investigation, leads to less radiation exposure, less pain and less costs.

Appetite control: methodological aspects of the evaluation of foods.

This report describes a set of scientific procedures used to assess the impact of foods and food ingredients on the expression of appetite (psychological and behavioural). An overarching priority has been to enable potential evaluators of health claims about foods to identify justified claims and to exclude claims that are not supported by scientific evidence for the effect cited. This priority follows precisely from the principles set down in the PASSCLAIM report. The report allows the evaluation of the strength of health claims, about the effects of foods on appetite, which can be sustained on the basis of the commonly used scientific designs and experimental procedures. The report includes different designs for assessing effects on satiation as opposed to satiety, detailed coverage of the extent to which a change in hunger can stand alone as a measure of appetite control and an extensive discussion of the statistical procedures appropriate for handling data in this field of research. Because research in this area is continually evolving, new improved methodologies may emerge over time and will need to be incorporated into the framework. One main objective of the report has been to produce guidance on good practice in carrying out appetite research, and not to set down a series of commandments that must be followed.

The effect of body weight changes and endurance training on 24h substrate oxidation.

OBJECTIVE: To investigate the effect of exercise training and dietary macronutrient composition on 24 h substrate oxidation in male, obese subjects. DESIGN: A 16 month exercise intervention study was executed, including a weight loss period with a very low energy diet (VLED) for 2 months at the start of the study. SUBJECTS: Twelve male, obese subjects (age 36.3+/-5.1 y; body weight 94.6+/-13.9 kg; body mass index, BMI 30.8+/-3.0 kg/m2) and in an additional study 15 lean, well-trained subjects (age 36.2+/-7.2 y; body weight 72.2+/-5.9 kg; BMI 22.3+/-1.7 kg/m2) participated. MEASUREMENTS: Substrate oxidation was measured during a standardized 36 h stay in the respiration chamber at the start of the study (0 months), and at 4, 10 and 16 months. In the respiration chamber subjects were randomly assigned to a high-fat (Hi.F) diet (60% of energy (En%) fat) or a reduced-fat (Red.F) diet (30 En% fat). The well-trained group was measured once in the respiration chamber for 36 h according to the same protocol. RESULTS: At any time point, independent of the diet consumed, the 24 h carbohydrate (CHO) balances in the chamber were mostly negative (means ranging from +31 to -98 g/d) and the fat balances mostly positive (means ranging from -26 to +38 g/d) for the obese a well as for the lean, well-trained group. For both diets an increased shortage of 70 g of CHO was found at 16 months compared with 4 months, and an increase in fat balance of 33 g during the same time period in the obese subjects, indicating that CHO oxidation had increased with 12 months endurance training. In the well-trained group the 24h CHO balance was even more negative for both types of diet (-103 to -185 g/d for the Red.F and Hi.F diet, respectively) under similar conditions compared with the trained obese group. CONCLUSION: The changes in 24 h substrate utilization in the obese, as well as in the well-trained group, suggest that endurance training increased the reliance on carbohydrate oxidation and therefore did not increase 24 fat oxidation.

Obesity, restrained eating and the cumulative intake curve.

The cumulative intake curves of 50 obese and 86 normal weight women during test meals were related to body mass index, age and the three factors of Stunkard & Messick's questionnaire (Journal of Psychosomatic Research, 29, 71-83), cognitive restraint, disinhibition and perceived hunger. Eating behaviour was monitored by a concealed camera and rate of intake via an electronic balance built into the table under the plate. The eating behaviour of each subject was very consistent over a series of three or six lunches of the same solid food consumed solitarily in a constant environment, with marked differences between subjects. Differences in body mass index over the whole sample were not related to the shape of the cumulative intake curve during test meals. In multiple regression analysis, the normal-weight subjects who scored high on disinhibition of restraint in response to emotions and external influences showed a more nearly constant rate of intake. In a separate multiple regression, the overweight subjects with the same characteristic showed a decelerating rate of intake. Susceptibility to hunger had no discernible relationship to the shape of the cumulative intake curve in either normal or overweight subjects. We conclude that the shape of the cumulative intake curve can be attributed more to cognitive than to biological factors.

Anal fistulotomy between Skylla and Charybdis.

OBJECTIVE: This study was undertaken to assess the results of anal fistulotomy on faecal continence, recurrence and satisfaction. METHODS: We reviewed the records of 60 patients who underwent anal fistulotomy between 1997 and 2000. Follow-up was by a questionnaire with 46 (77%) patients responding. Mean follow-up was 1-4 years. Fistulas were intersphincteric in 12 patients and transsphincteric in 34 patients. Operative procedure consisted of fistulotomy. RESULTS: Of 11 patients with high fistula, 9 (82%) had impaired continence; Of 17 patients with midanal fistula, 4 (24%) suffered impaired continence. Eighteen patients had a low fistula and 8 (44%) developed impaired continence. In the whole group 50% had suffered faecal incontinence. There were no recurrences and there was satisfaction with the situation in 87% of patients. CONCLUSIONS: Fistulotomy for primary fistula in ano in this retrospective study with a follow-up up to 4 years was associated with no recurrences. Eighty-two percent of patients with a high anal opening have impaired faecal continence, nevertheless patients' satisfaction is high.