Limited wedge resection for T1 colon cancer (LIMERIC-II trial) - rationale and study protocol of a prospective multicenter clinical trial.

BACKGROUND: The sole presence of deep submucosal invasion is shown to be associated with a limited risk of lymph node metastasis. This justifies a local excision of suspected deep submucosal invasive colon carcinomas (T1 CCs) as a first step treatment strategy. Recently Colonoscopy-Assisted Laparoscopic Wedge Resection (CAL-WR) has been shown to be able to resect pT1 CRCs with a high R0 resection rate, but the long term outcomes are lacking. The aim of this study is to evaluate the safety, effectiveness and long-term oncological outcomes of CAL-WR as primary treatment for patients with suspected superficial and also deeply-invasive T1 CCs. METHODS: In this prospective multicenter clinical trial, patients with a macroscopic and/or histologically suspected T1 CCs will receive CAL-WR as primary treatment in order to prevent unnecessary major surgery for low-risk T1 CCs. To make a CAL-WR technically feasible, the tumor may not include > 50% of the circumference and has to be localized at least 25 cm proximal from the anus. Also, there should be sufficient distance to the ileocecal valve to place a linear stapler. Before inclusion, all eligible patients will be assessed by an expert panel to confirm suspicion of T1 CC, estimate invasion depth and subsequent advise which local resection techniques are possible for removal of the lesion. The primary outcome of this study is the proportion of patients with pT1 CC that is curatively treated with CAL-WR only and in whom thus organ-preservation could be achieved. Secondary outcomes are 1) CAL-WR's technical success and R0 resection rate for T1 CC, 2) procedure-related morbidity and mortality, 3) 5-year overall and disease free survival, 4) 3-year metastasis free survival, 5) procedure-related costs and 6) impact on quality of life. A sample size of 143 patients was calculated. DISCUSSION: CAL-WR is a full-thickness local resection technique that could also be effective in removing pT1 colon cancer. With the lack of current endoscopic local resection techniques for > 15 mm pT1 CCs with deep submucosal invasion, CAL-WR could fill the gap between endoscopy and major oncologic surgery. The present study is the first to provide insight in the long-term oncological outcomes of CAL-WR. TRIAL REGISTRATION: CCMO register (ToetsingOnline), NL81497.075.22, protocol version 2.3 (October 2022).

Urinary Biomarkers in a Living Donor Kidney Transplantation Cohort-Predictive Value on Graft Function.

Early non-invasive detection and prediction of graft function after kidney transplantation is essential since interventions might prevent further deterioration. The aim of this study was to analyze the dynamics and predictive value of four urinary biomarkers: kidney injury molecule-1 (KIM-1), heart-type fatty acid binding protein (H-FABP), N-acetyl-ß-D-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) in a living donor kidney transplantation (LDKT) cohort. Biomarkers were measured up to 9 days after the transplantation of 57 recipients participating in the VAPOR-1 trial. Dynamics of KIM-1, NAG, NGAL, and H-FABP significantly changed over the course of 9 days after transplantation. KIM-1 at day 1 and NAG at day 2 after transplantation were significant predictors for the estimated glomerular filtration rate (eGFR) at various timepoints after transplantation with a positive estimate (p < 0.05), whereas NGAL and NAG at day 1 after transplantation were negative significant predictors (p < 0.05). Multivariable analysis models for eGFR outcome improved after the addition of these biomarker levels. Several donor, recipient and transplantation factors significantly affected the baseline of urinary biomarkers. In conclusion, urinary biomarkers are of added value for the prediction of graft outcome, but influencing factors such as the timing of measurement and transplantation factors need to be considered.

Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions: A Prospective Multicenter Cohort Study (LIMERIC-Study).

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. SUMMARY BACKGROUND DATA: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. METHODS: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. RESULTS: Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. CONCLUSIONS: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.

Locoregional recurrences after transanal total mesorectal excision of rectal cancer during implementation.

BACKGROUND: Transanal total mesorectal excision (TaTME) has been proposed as an approach in patients with mid and low rectal cancer. The TaTME procedure has been introduced in the Netherlands in a structured training pathway, including proctoring. This study evaluated the local recurrence rate during the implementation phase of TaTME. METHODS: Oncological outcomes of the first ten TaTME procedures in each of 12 participating centres were collected as part of an external audit of procedure implementation. Data collected from a cohort of patients treated over a prolonged period in four centres were also collected to analyse learning curve effects. The primary outcome was the presence of locoregional recurrence. RESULTS: The implementation cohort of 120 patients had a median follow up of 21·9 months. Short-term outcomes included a positive circumferential resection margin rate of 5·0 per cent and anastomotic leakage rate of 17 per cent. The overall local recurrence rate in the implementation cohort was 10·0 per cent (12 of 120), with a mean(s.d.) interval to recurrence of 15·2(7·0) months. Multifocal local recurrence was present in eight of 12 patients. In the prolonged cohort (266 patients), the overall recurrence rate was 5·6 per cent (4·0 per cent after excluding the first 10 procedures at each centre). CONCLUSION: TaTME was associated with a multifocal local recurrence rate that may be related to suboptimal execution rather than the technique itself. Prolonged proctoring, optimization of the technique to avoid spillage, and quality control is recommended.

ANTECEDENTES: La escisión total del mesorrecto por vía transanal (Transanal Total Mesorectal Excision, TaTME) se ha propuesto como abordaje quirúrgico en pacientes con cáncer de recto medio e inferior. La técnica TaTME se ha introducido en los Países Bajos mediante un proceso de formación estructurado que incluye la supervisión. Este estudio evaluó el porcentaje de recidiva local durante la fase de implementación de TaTME. MÉTODOS: Se recogieron los resultados oncológicos de los primeros 10 procedimientos realizados mediante TaTME en cada uno de los 12 centros participantes como parte de una auditoría externa de implementación del procedimiento. Se reunió una cohorte más amplia de pacientes procedentes de 4 centros para analizar los efectos de la curva de aprendizaje. El criterio de valoración principal fue la presencia de recidiva locorregional. RESULTADOS: La cohorte de implementación de 120 pacientes tuvo una mediana de seguimiento de 21,9 meses. Los resultados a corto plazo incluyeron una tasa del margen de resección circunferencial positivo del 5% y una tasa de fuga anastomótica del 17,4%. La tasa global de recidiva local en la cohorte de implementación fue del 10% (12/120) con un intervalo medio de recidiva de 15,2 (DE 7) meses. El patrón de recidiva local fue multifocal en 8 de 12 casos (67%). En la cohorte ampliada (n = 266), la tasa global de recidiva fue del 5,6% (4,0%, excluyendo a los primeros 10 pacientes). CONCLUSIÓN: TaTME se asoció con un porcentaje de recidiva local multifocal que puede relacionarse con una ejecución subóptima, más que con la técnica en sí. Se recomienda una supervisión prolongada, la optimización de la técnica para evitar la diseminación tumoral, así como un control de calidad.

Determinants of improved survival after oesophagectomy for cancer.

BACKGROUND: Survival after oesophagectomy for cancer seems to be improving. This study aimed to identify the most important contributors to this change. METHODS: Patients who underwent oesophagectomy from 1999 to 2010 were extracted from the Netherlands Cancer Registry. Four time periods were compared: 1999-2001 (period 1), 2002-2004 (period 2), 2005-2007 (period 3) and 2008-2010 (period 4). Hospital type, tumour location, tumour type, tumour differentiation, neoadjuvant therapy, operation type, (y)pT category, involvement of surgical resection margins, number of removed lymph nodes and number of involved lymph nodes were investigated in relation to trends in survival using multivariable analysis. RESULTS: A total of 4382 patients were identified. Two-year overall survival rates improved from 49·3 per cent in period 1 to 58·4, 56·2 and 61·0 per cent in periods 2, 3 and 4 respectively (P < 0·001). Multivariable survival analysis revealed that the improvement in survival between periods 3 and 4 was related to the introduction of neoadjuvant therapy. The improvement in survival between periods 1 and 2 could not be explained completely by the factors studied. The number of examined lymph nodes increased, especially between periods 2 and 3, but this increase was not associated with the improvement in survival. CONCLUSION: The observed increase in long-term survival after surgery for oesophageal cancer between 1999 and 2010 in the Netherlands is difficult to explain fully, although the recent increase seems to be partly attributable to the introduction of neoadjuvant therapy.

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

OBJECTIVES: We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. BACKGROUND: Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. METHODS: Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. RESULTS: One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). CONCLUSIONS: The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

The 30-day versus in-hospital and 90-day mortality after esophagectomy as indicators for quality of care.

OBJECTIVE: To describe causes of death in the first year after esophagectomy and determine the time frame that should be used for measurement of quality of surgery. A case-mix adjustment model was developed for the comparison between hospitals. BACKGROUND: The time period in which postoperative mortality should be measured as a performance indicator is debated. METHODS: Cause of death was identified for patients in a tertiary referral hospital who died within 1 year after surgery and classified as surgery related or not surgery related. Sensitivity and specificity for detecting deaths related to surgery were calculated for different periods of follow-up. Case-mix adjustment models for 30-day mortality (30DM), in-hospital mortality, and 90-day mortality (90DM) were developed. RESULTS: In total, 1282 patients underwent esophagectomy. 30DM was 2.9%, the in-hospital mortality rate was 5.1% and 90DM was 7%. Beyond 30 days, a substantial number of deaths were related to the operation, especially due to anastomotic leakage. Postdischarge nononcological mortality was most frequently caused by sudden death. One in 5 patients died because of recurrent disease, being the most important threat in the first year after surgery. The 30DM had a sensitivity for detecting surgery-related deaths of 33% and a specificity of 100%. The 90DM had a sensitivity of 74% and a specificity of 96%. CONCLUSIONS: A period of postoperative follow-up longer than 30 days needs to be considered when comparing surgical performance between institutes. In the case-mix adjustment model for 90DM, no other variables have to be taken into account compared to those involved in 30DM.

Re-resection rates after breast-conserving surgery as a performance indicator: introduction of a case-mix model to allow comparison between Dutch hospitals.

AIM: Re-resection rate after breast-conserving surgery (BCS) has been introduced as an indicator of quality of surgical treatment in international literature. The present study aims to develop a case-mix model for re-resection rates and to evaluate its performance in comparing results between hospitals. METHODS: Electronic records of eligible patients diagnosed with in-situ and invasive breast cancer in 2006 and 2007 were derived from 16 hospitals in the Rotterdam Cancer Registry (RCR) (n = 961). A model was built in which prognostic factors for re-resections after BCS were identified and expected re-resection rate could be assessed for hospitals based on their case mix. To illustrate the opportunities of monitoring re-resections over time, after risk adjustment for patient profile, a VLAD chart was drawn for patients in one hospital. RESULTS: In general three out of every ten women had re-surgery; in about 50% this meant an additive mastectomy. Independent prognostic factors of re-resection after multivariate analysis were histological type, sublocalisation, tumour size, lymph node involvement and multifocal disease. After correction for case mix, one hospital was performing significantly less re-resections compared to the reference hospital. On the other hand, two were performing significantly more re-resections than was expected based on their patient mix. CONCLUSIONS: Our population-based study confirms earlier reports that re-resection is frequently required after an initial breast-conserving operation. Case-mix models such as the one we constructed can be used to correct for variation between hospitals performances. VLAD charts are valuable tools to monitor quality of care within individual hospitals.

Evaluation of the pressure ulcer prevention clinical decision report for bedside nurses in acute care hospitals.

BACKGROUND: Hospital stays for patients with pressure ulcers (PU) increased nearly 80% from 1992 to 2006. Most PU's developed during an admission, often despite preventive efforts from clinical staff. Data from Electronic medical records (EMR's) were used to prepare daily patient risk factor and PU information for nurses to help prevent PU development and exacerbations. OBJECTIVES: THE OBJECTIVES OF THIS STUDY WERE TO DETERMINE WHETHER: 1) dissemination of an automated daily report with patient risk and current status of pressure ulcers ("PU Daily") helps prevent the development of pressure ulcers, and 2) using the PU Daily information impacts the severity of pressure ulcers that develop in an acute care setting. METHODS: A pre-post study with four control units was designed to determine the impact of the PU Daily in intensive care units (ICU) in a large medical center. The control units included ICU's using the same EMR and similar complexity of cases with a high risk of developing a PU. The pre-post study took place over a six month period (March - August 2009). RESULTS: A total of 6,735 cases were included in the study. The intervention unit showed a significant decrease (p = 0.004) in PU's at post-evaluation; none of the four comparison units showed a decrease at the p<0.05 level. The intervention led to a significant reduction in the total number of PU's documented (p <0.000) and the number of Stage II PU's (p = 0.046). CONCLUSION: The intervention with the PU Daily showed a significant decrease in the total PU's and severity of PU's and allowed for implementation of interventions that help prevent the development of PU's. As EMR's become more widely available, this intervention showed a reduction in PU's. Future studies should further develop this intervention and include multiple institutions and patient populations.

Differences in oral health behaviour between children from high and children from low SES schools in The Netherlands.

OBJECTIVE: To identify the determinants of dental caries in relation to socio-economic status (SES) within oral health, children's eating habits and parental attitudes towards oral health. BASIC RESEARCH DESIGN: Dental screening data were collected from 6- and 10-year-old schoolchildren from low and high SES schools in The Netherlands in this cross-sectional study. METHODS: The clinical examination was performed by trained dental hygiene students who collected the data on dental caries, dental plaque and duration of brushing. The paper questionnaire completed by the parents included 18 questions about oral health behaviour, eating habits and parental attitudes towards oral health. RESULTS: Two of the six parameters of oral health behaviour were statistically associated with the high caries prevalence in the low SES group (brushing frequency (p = 0.028) and age at the first visit to the dentist (p = 0.044)). High intake of fruit juices and/or soft drinks (p = 0.043) and low calcium intake (p = 0.028) were identified as risk determinants for caries with low SES. All parameters of parental attitudes towards oral health were associated with caries, but not with SES. CONCLUSIONS: This study confirmed that the high caries prevalence in children from low SES schools was associated with oral health behaviour and eating habits. The role of parents was indirectly associated with the occurrence of dental caries. Therefore, it is important to include parents in all intervention programmes in order to reduce the prevalence of caries.

Corrections for inhomogeneities in biological tissue caused by blood vessels.

In tissue optics, the assumption that blood is homogeneously distributed in tissue can give rise to miscalculations because blood is found only in blood vessels. In our paper randomly oriented blood vessels are treated as particles for which we obtained apparent absorption and scattering coefficients by means of the Monte Carlo method. Apart from this correction for the contribution of blood properties in tissue, a correction for the contribution of the surrounding tissue proved to be needed as well. The results found with our model were compared with available results from the literature.

Nursing and health care for an aging society: the case of The Netherlands.

1. Demographic developments in European and western countries are not unique. Nurses should embrace the opportunity to learn from each others' care and research initiatives for the elderly population. 2. Current transitions in health care systems should be seized as an opportunity to further establish and develop the nursing profession, for example, through joining and initiating multidisciplinary initiatives. 3. The aging population is the fastest growing population in a number of countries. The training, recruitment, and retainment of nursing staff are key to continuously provide high quality care for the elderly.

Predictors of progress in smoking cessation.

This study examined the ability of two specific measures of stressors associated with smoking cessation to act as predictors of progress through the stages of smoking cessation as described by Prochaska and DiClemente (1983). Specifically, a 19-item scale measuring barriers to smoking cessation and a 14-item scale measuring smoking cessation self-efficacy were completed by 127 smokers and self-quitters at three time points over a six-month period. Subjects who made progress through the stages of smoking cessation had lower barriers scores initially and had significant changes in their self-efficacy and barriers scores over the six-month period. In contrast, non-progressors had no significant changes in either their self-efficacy or barriers scores over the time period. These results suggest that the two scales may provide clinically useful data to public health nurses working with smokers.

Development and testing of the barriers to cessation scale.

The purpose of this research was to develop and test a measure of barriers to smoking cessation. Barriers, reconceptualized within the Transactional Model of Stress (Lazarus, 1966), reflect specific stressors associated with smoking cessation. The measure consists of a 19-item scale, which has been tested in three studies. Cronbach's alpha coefficients ranged from .81 to .87. Construct validity was demonstrated by correlations between barriers scores and scores on the Daily Hassles Scale (DeLongis, Folkman, & Lazarus, 1988). Predictive validity was demonstrated by findings that barriers scores significantly contributed to classification of abstainers versus relapsers 8 weeks after smoking cessation group participants quit smoking.

Medical practice-based influenza surveillance: viral prevalence and assessment of morbidity.

Regular surveillance of influenza virus activity and associated illness is necessary to monitor changes in circulating strains. As part of a demonstration project, medical practices in a seven-county area in southern lower Michigan were recruited as sentinel surveillance sites. The practices were asked to collect specimens for virus isolation and/or data on age-specific frequency of respiratory illnesses that met a case definition. Data were used to establish periods of influenza virus activity for vaccine effectiveness determinations. Over three study periods, 1989-1992, there were documented outbreaks of influenza type A(H3N2), type A(H1N1), and type B. The incidence of influenza-like illness increased during these outbreaks, with variation in age-specific frequency from year to year. Recovery of virus was not affected during the winter season by long delays in specimen receipt by the laboratory. Results indicated that medical practices can be successfully recruited as surveillance sites to provide information on the timing, etiology, and intensity of acute respiratory illness.

Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly.

During the winter of 1989-1990, influenza type A(H3N2) circulated widely, causing excess morbidity and mortality nationwide. From November through April, 1989-1990, hospitalized cases of pneumonia and influenza occurring among noninstitutionalized individuals 65 or more years of age were identified by 20 acute care hospitals in southern lower Michigan. These cases were group matched on age, sex, race, and zip code to randomly sampled, community-based controls from a comprehensive listing of Medicare beneficiaries residing in the study area. Self-reported data were collected from cases and controls on influenza vaccine status for the 1989-1990 season and on a number of other factors which could have influenced vaccination status or outcome. Questionnaires were completed by 1,907 individuals, 449 of whom were cases, resulting in an overall response rate of 76%. A community-based influenza surveillance system was implemented to determine the timing and intensity of viral activity and influenza-like illness. Vaccine effectiveness in preventing overall pneumonia and influenza hospitalizations was estimated by logistic regression. During the 3-month period of surveillance-confirmed peak influenza type A(H3N2) circulation, vaccine effectiveness was 45% (95% confidence interval 14-64, p = 0.009). However, during the 3-month period of low or absent virus activity, identical methodology and model specification resulted in an effectiveness estimate of 21% that was not statistically different from zero (p = 0.36). The effectiveness determined during the peak period of virus circulation is felt to be a conservative estimate, since agents other than influenza are responsible for pneumonia and influenza hospitalizations, even during times of peak influenza activity.