Real Life Data and Outcome of FOLFIRINOX Use in Metastatic Pancreatic Cancer Patients in General Hospitals in the Netherlands.

INTRODUCTION: Pancreatic cancer is one of the five most common causes of cancer mortality in developed countries. In patients with metastatic disease, the most frequent treatment used is FOLFIRINOX, which is associated with moderate toxicity which could influence quality of life. The efficacy of FOLFIRINOX in a general population in the Netherlands has not been subject of research before, and therefore, this research has been set up in order to investigate what the real-life benefits of FOLFIRINOX are in a population with metastatic pancreatic cancer (mPC) treated in three general hospitals in the Netherlands. METHODS: The data used in this study was collected by patient records leading to a noninterventional retrospective cohort study. Eighty-six patients, over 18 years of age, diagnosed with mPC between the years 2015 and 2022 and treated with FOLFIRINOX at Maasstad Hospital in Rotterdam, Amphia Hospital in Breda, or Catharina Hospital in Eindhoven, were included in the study. Kaplan-Meier models were used in order to represent survival outcomes. RESULTS: The results showed a median overall survival of 228 days (IQR 118-355). Only 14.0% (n = 12) completed the first-line treatment, and 51.2% (n = 44) of patients stopped treatment before or during cycle 6. Toxicity is highest, grade 3, after the first cycle but remains high for grade 1 and 2 during all treatment cycles. CONCLUSION: Survival rates for patient with metastatic pancreatic cancer treated with FOLFIRINOX were worse in our study population than in comparative studies.

Practice variation in Sentinel Lymph Node Biopsy for melanoma patients in different geographical regions in the Netherlands.

BACKGROUND: Due to the lack of solid evidence for treatment benefit of Sentinel Lymph Node Biopsy (SLNB) as part of loco-regional surgical treatment of non-distant metastatic melanoma, there might be variation in surgical treatment strategies in the Netherlands. The objective of the current study was to assess differences in the performance of SLNB, in geographical regions in the Netherlands, of non-distant metastatic melanoma patients (American Joint Committee on Cancer (AJCC) stage I-III). MATERIALS AND METHODS: A total of 28 550 melanoma patients, diagnosed between 2005 and 2013, were included in this population based retrospective study. Data were retrieved from the Netherlands Cancer Registry (NCR). Treatment strategies in 8 regions of the Netherlands were compared according to stage, excluding patients with distant metastasis (AJCC stage IV). RESULTS: Throughout the Netherlands, there was substantial practice variation across the regions. The performance of SLNB in patients with clinically unsuspected lymph nodes and Breslow thickness >1.0 mm was significantly different between the regions. In a post hoc analysis, we observed that patients aged over 60 years, female patients and patients with a melanoma located in head and neck have lower odds to receive a SLNB. CONCLUSION: There is considerable loco-regional practice variation which cannot completely be explained by the patient and tumor characteristics, in the surgical treatment of non-distant metastatic melanoma patients in the Netherlands. Although national guidelines recommend considering SLNB in all patients with a melanoma thicker than 1 mm, only half of the patients received a SLNB. Future research should assess whether this practice variation leads to unwanted variations in clinical outcome.

Lactulose as a marker of intestinal barrier function in pigs after weaning.

Intestinal barrier function in pigs after weaning is almost exclusively determined in terminal experiments with Ussing chambers. Alternatively, the recovery in urine of orally administered lactulose can be used to assess intestinal permeability in living animals. This experiment was designed to study the barrier function of the small intestine of pigs over time after weaning. The aim was to relate paracellular barrier function (measured by lactulose recovery in the urine) with macromolecular transport [measured by horseradish peroxidase (HRP) using Ussing chambers] and bacterial translocation to assess whether lactulose recovery is related to possible causes of infection and disease. Forty gonadectomized male pigs (6.7 ± 0.6 kg) were weaned (d 0) at a mean age of 19 d, fitted with urine collection bags, and individually housed. Pigs were dosed by oral gavage with a marker solution containing lactulose (disaccharide) and the monosaccharides l-rhamnose, 3-O-methylglucose, and d-xylose at 2 h and at 4, 8, and 12 d after weaning. The recovery of sugars in the urine was determined over 18 h after each oral gavage. The day after each permeability test, the intestines of 10 pigs were dissected to determine bacterial translocation to the mesenteric lymph nodes and jejunal permeability for HRP in Ussing chambers. Recovery of l-rhamnose in urine was affected by feed intake and by the time after weaning (P ≤ 0.05). Recovery of lactulose from the urine was greater (P ≤ 0.05) at 4, 8, and 12 d after weaning compared with the first day after weaning and was negatively correlated with feed intake (r = -0.63, P ≤ 0.001). The mean translocation of aerobic bacteria to the mesenteric lymph nodes was greater at 5 and 13 d after weaning compared with d 1 (P ≤ 0.05). Lactulose recovery showed no correlation with permeability for HRP nor with bacterial translocation (P > 0.05). Although both lactulose recovery and bacterial translocation increased over time after weaning, lactulose recovery did not correlate with the permeability for HRP nor bacterial translocation within a pig (P > 0.05). Therefore, we conclude that lactulose recovery in the urine of pigs after weaning is not associated with risk factors for infections. However, it appears to be possible to measure paracellular barrier function with orally administered lactulose in pigs shortly after weaning. Further studies will reveal whether this variable is relevant for the long-term performance or health of pigs after weaning.