Treatment and overall survival of four types of non-metastatic periampullary cancer:nationwide population-based cohort study

Background: Periampullary adenocarcinoma consists of pancreatic adenocarcinoma (PDAC), distal cholangiocarcinoma (DC), ampullary cancer (AC), and duodenal adenocarcinoma (DA). The aim of this study was to assess treatment modalities and overall survival by tumor origin. Methods: Patients diagnosed with non-metastatic periampullary cancer in 2012–2018 were identified from the Netherlands Cancer Registry. OS was studied with Kaplan–Meier analysis and multivariable Cox regression analyses, stratified by origin. Results: Among the 8758 patients included, 68% had PDAC, 13% DC, 12% AC, and 7% DA. Resection was performed in 35% of PDAC, 56% of DC, 70% of AC, and 59% of DA. Neoadjuvant and/or adjuvant therapy was administered in 22% of PDAC, 7% of DC, 7% of AC, and 12% of DA. Three-year OS was highest for AC (37%) and DA (34%), followed by DC (21%) and PDAC (11%). Adjuvant therapy was associated with improved OS among PDAC (HR = 0.62; 95% CI 0.55–0.69) and DC (HR = 0.69; 95% CI 0.48–0.98), but not AC (HR = 0.87; 95% CI 0.62–1.22) and DA (HR = 0.85; 95% CI 0.48–1.50). Conclusion: This retrospective study identified considerable differences in treatment modalities and OS between the four periampullary cancer origins in daily clinical practice. An improved OS after adjuvant chemotherapy could not be demonstrated in patients with AC and DA

Parelsnoer institute biobank hereditary colorectal cancer: A joint infrastructure for patient data and biomaterial on hereditary colorectal cancer in the Netherlands

Each year approximately 15,000 patients are diagnosed with colorectal cancer (CRC) in the Netherlands, of whom 5-10% are associated with a hereditary syndrome. To enable future research into hereditary CRC, we established a collaborative biobank for hereditary CRC in all eight University Medical Centers (UMCs) in the Netherlands in 2009. This Biobank Hereditary CRC is part of the Parelsnoer Institute (PSI), which is funded by the Dutch Federation of UMCs and the Dutch Government. Besides the multicenter collaboration, the multidisciplinary nature of this biobank - involving Gastroenterology, Genetics and Surgery - is essential for its functionality and value.Patients at increased risk of hereditary CRC and/or Polyposis, or with a proven germline mutation causing CRC and/or Polyposis are included. Both clinical data (demographic data, details on medical and family history, information on surveillance, endoscopy and surgery, results of microsatellite instability and molecular genetic tests) and biomaterial (DNA, plasma, serum and tissue) are collected in a standardized manner

Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma:a nationwide analysis

Introduction: Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). Aim: assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. Patients and methods: Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014–2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). Results: 691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89–100%), SFM-b6 was 44% (20–77%), and SFM-b5+6 was 65% (53–90%). All centers met the performance target RAS>85%. Only 9 out of 17 met the performance target SFM-b5+6 > 85%. Conclusion: This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated

Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS):study protocol for a nationwide prospective cohort study

INTRODUCTION: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. METHODS AND ANALYSIS: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months. ETHICS AND DISSEMINATION: PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NL7066). Prospectively registered

Endoscopic Botulinum Toxin for Gastroparesis: Results of a Retrospective Series

Beneficial effects of pyloric botulinum toxin injection have been described in a subgroup of gastroparesis patients. Our aim is to evaluate whether clinical, manometric and/or scintigraphic parameters are able to predict treatment outcome. Forty patients (67% female, age 49 (36–56) years) with decompensated gastroparesis treated with botulinum toxin were included in this retrospective analysis. Objective parameters were high-resolution antroduodenal manometry, gastric emptying rate (scintigraphy), and weight change. Subjective treatment outcome was assessed with a Global Physician Assessment Scale. Binary logistic regression analysis was performed to identify predictors for treatment outcome. Fourteen patients (35%) were symptom-responders, and 65% of patients were short-term weight-responders. For both subjective and objective treatment outcome, no differences were found in manometric and scintigraphic variables between responders and non-responders. Neither clinical nor manometric or scintigraphic variables could predict subjective and objective treatment outcome. In conclusion, symptom improvement is achieved in a subgroup of gastroparesis patients treated with endoscopic pyloric botulinum toxin. Although the majority of patients were able to maintain their baseline weight at short-term follow-up, a substantial group of patients needed nutritional interventions on long-term follow-up. However, none of the demographic, clinical, scintigraphic, or antroduodenal manometry variables were able to predict either subjective or objective treatment outcome

Metachronous neoplasms in patients with laterally spreading tumours during surveillance

BACKGROUND: Laterally spreading tumours represent a major challenge for endoscopic detection and resection. OBJECTIVE: To examine synchronous and metachronous neoplasms in patients with laterally spreading tumours. METHODS: We prospectively collected colonoscopy and histopathology data from patients who underwent colonoscopy in our centre at up to 6 years' follow‐up. Post‐resection surveillance outcomes between laterally spreading tumours, flat colorectal neoplasms 10 mm or greater, and large polypoid colorectal neoplasms, polypoid colorectal neoplasms 10 mm or greater, were compared. RESULTS: Between 2008 and 2012, 8120 patients underwent colonoscopy for symptoms (84.6%), screening (6.7%) or surveillance (8.7%). At baseline, 151 patients had adenomatous laterally spreading tumours and 566 patients had adenomatous large polypoid colorectal neoplasms. Laterally spreading tumour patients had more synchronous colorectal neoplasms than large polypoid colorectal neoplasm patients (mean 3.34 vs. 2.34, p < 0.001). Laterally spreading tumour patients significantly more often developed metachronous colorectal neoplasms (71.6% vs. 54.2%, p = 0.0498) and colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients (36.4% vs. 15.8%, p < 0.001). After correction for age and gender, laterally spreading tumour patients were more likely than large polypoid colorectal neoplasm patients to develop a colorectal neoplasm with high grade dysplasia or submucosal invasion (hazard ratio 2.9, 95% confidence interval 1.8–4.6). The risk of metachronous colorectal cancer was not significantly different in laterally spreading tumours compared to large polypoid colorectal neoplasm patients. CONCLUSION: Patients with laterally spreading tumours developed more metachronous colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients. Based on these findings endoscopic treatment and surveillance recommendations for patients with laterally spreading tumours should be optimised

BioXmark® liquid fiducials to enable radiotherapy tumor boosting in rectal cancer, a feasibility trial

BACKGROUND AND PURPOSE: Dose-escalation in rectal cancer (RCa) may result in an increased complete response rate and thereby enable omission of surgery and organ preservation. In order to implement dose-escalation, it is crucial to develop a technique that allows for accurate image-guided radiotherapy. The aim of the current study was to determine the performance of a novel liquid fiducial marker (BioXmark®) in RCa patients during the radiotherapy course by assessing its positional stability on daily cone-beam CT (CBCT), technical feasibility, visibility on different imaging modalities and safety. MATERIALS AND METHODS: Prospective, non-randomized, single-arm feasibility trial with inclusion of twenty patients referred for neoadjuvant chemoradiotherapy for locally advanced RCa. Primary study endpoint was positional stability on CBCT. Furthermore, technical aspects, safety and clinical performance of the marker, such as visibility on different imaging modalities, were evaluated. RESULTS: Seventy-four markers from twenty patients were available for analysis. The marker was stable in 96% of the cases. One marker showed clinically relevant migration, one marker was lost before start of treatment and one marker was lost during treatment. Marker visibility was good on computed tomography (CT) and CBCT, and moderate on electronic portal imaging (EPI). Marker visibility on magnetic resonance imaging (MRI) was poor during response evaluation. CONCLUSION: The novel liquid fiducial marker demonstrated positional stability. We provide evidence of the feasibility of the novel fiducial marker for image-guided radiotherapy on daily cone beam CT for RCa patients

Optical diagnosis of diminutive polyps in the Dutch Bowel Cancer Screening Program: Are we ready to start?

Background and study aims Implementation of optical diagnosis of diminutive polyps may potentially increase the efficacy and cost-effectiveness of colonoscopies. To adopt such strategy in clinical practice, the Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) thresholds provide the basis to be met: >= 90 % negative predictive value (NPV) for diagnosis of adenomatous histology and >= 90 % agreement on surveillance intervals. We evaluated this within the Dutch Bowel Cancer Screening Program (BCSP). Patients and methods Endoscopic and histological data were collected from participants of the national bowel cancer screening program with an unfavorable fecal immunochemical test referred for colonoscopy between February 2014 and August 2015 at four endoscopy centers. The "resect and discard" scenario was studied, resecting diminutive polyps without histological evaluation. Agreement between optical diagnosis and histological diagnosis was measured for surveillance intervals according to Dutch, European and American post-polypectomy surveillance guideline. Results Fifteen certified endoscopists participated in this study and included 3028 diminutive polyps. In 2,330 patients both optical and histological diagnosis were available. Optical diagnosis of diminutive polyps showed NPV of 84 % (95 % CI 80-87) for adenomatous histology in the rectosigmoid. Applying the 'resect and discard' strategy resulted in 90.6 %, 91.2 %, 90.9 % agreement on surveillance intervals for the Dutch, European and American guideline respectively. Conclusion Our data representing current clinical practice in the Dutch BCSP practice on optical diagnosis of diminutive polyps showed that accuracy of predicting histology remains challenging, and risk of incorrect optical diagnosis is still significant. Therefore, it is too early to safely implement these strategies

Optical diagnosis of diminutive polyps in the Dutch Bowel Cancer Screening Program:Are we ready to start?

Background and study aims Implementation of optical diagnosis of diminutive polyps may potentially increase the efficacy and cost-effectiveness of colonoscopies. To adopt such strategy in clinical practice, the Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) thresholds provide the basis to be met: >= 90 % negative predictive value (NPV) for diagnosis of adenomatous histology and >= 90 % agreement on surveillance intervals. We evaluated this within the Dutch Bowel Cancer Screening Program (BCSP). Patients and methods Endoscopic and histological data were collected from participants of the national bowel cancer screening program with an unfavorable fecal immunochemical test referred for colonoscopy between February 2014 and August 2015 at four endoscopy centers. The "resect and discard" scenario was studied, resecting diminutive polyps without histological evaluation. Agreement between optical diagnosis and histological diagnosis was measured for surveillance intervals according to Dutch, European and American post-polypectomy surveillance guideline. Results Fifteen certified endoscopists participated in this study and included 3028 diminutive polyps. In 2,330 patients both optical and histological diagnosis were available. Optical diagnosis of diminutive polyps showed NPV of 84 % (95 % CI 80-87) for adenomatous histology in the rectosigmoid. Applying the 'resect and discard' strategy resulted in 90.6 %, 91.2 %, 90.9 % agreement on surveillance intervals for the Dutch, European and American guideline respectively. Conclusion Our data representing current clinical practice in the Dutch BCSP practice on optical diagnosis of diminutive polyps showed that accuracy of predicting histology remains challenging, and risk of incorrect optical diagnosis is still significant. Therefore, it is too early to safely implement these strategies

A population-based study on incidence, treatment, and survival in ampullary cancer in the Netherlands

Introduction: Ampullary cancer is rare and as a result epidemiological data are scarce. The aim of this population-based study was to determine the trends in incidence, treatment and overall survival (OS) in patients with ampullary adenocarcinoma in the Netherlands between 1989 and 2016. Methods: Patients diagnosed with ampullary adenocarcinoma were identified from the Netherlands Cancer Registry. Incidence rates were age-adjusted to the European standard population. Trends in treatment and OS were studied over (7 years) period of diagnosis, using Kaplan-Meier and Cox regression analyses for OS and stratified by the presence of metastatic disease. Results: In total, 3840 patients with ampullary adenocarcinoma were diagnosed of whom, 55.0% were male and 87.1% had non-metastatic disease. The incidence increased from 0.59 per 100,000 in 1989-1995 to 0.68 per 100,000in 2010-2016. In non-metastatic disease, the resection rate increased from 49.5% in 1989-1995 to 63.9% in 2010-2016 (p < 0.001). The rate of adjuvant therapy increased from 3.1% to 7.9%. In non-metastatic disease, five-year OS (95% CI) increased from 19.8% (16.9-22.8) in 1989-1995 to 29.1% (26.0-31.2) in 2010e2016 (logrank p < 0.001). In patients with metastatic disease, median OS did not significantly improve (from 4.4 months (3.6-5.0) to 5.9 months (4.7-7.1); logrank p = 0.06). Cancer treatment was an independent prognostic factor for OS among all patients. Conclusion: Both incidence and OS of ampullary cancer increased from 1989 to 2016 which is most likely related to the observed increased resection rates and use of adjuvant therapy. (C) 2021 The Authors. Published by Elsevier Ltd