Attitudes toward genetic testing, family planning and preimplantation genetic testing in families with a germline CDKN2A pathogenic variant.

Individuals with a germline CDKN2A pathogenic variant (PV) have a highly increased life time risk of melanoma and pancreatic cancer. This cross-sectional study assessed the attitudes among toward genetic testing, family planning, and preimplantation genetic testing (PGT) in confirmed CDKN2A PV carriers and individuals with a 50% risk of the PV (at-risk carriers) using of a one-time questionnaire.A total of 537 individuals were screened for eligibility, of whom 208 of 366 (57%) confirmed carriers (56% female, median age 54 years [IQR 46-63]) and 39 of 171 (23%) at-risk carriers (59% female, median age of 26 years [IQR 22-32]) participated in the study. Primary motivations for genetic testing were to gain control over their personal and children's cancer risk, as well as increasing cancer surveillance practices. In contrast, concerns about obtaining a mortgage and life insurance were frequently cited as reasons for postponing genetic testing. Family planning decisions remained largely unaffected in both confirmed and at-risk carriers; however, the majority of confirmed carriers were still unaware of their familial or personal cancer risk when starting a family. More than 60% of the participants were unfamiliar with PGT and only a minority (19% of confirmed carriers and 10% of at-risk carriers) would be open to considering PGT as a reproductive option. This study found different attitudes toward genetic testing, family planning, and PGT among individuals affected by the CDKN2A PV. Understanding these different attitudes can help clinicians to address the complexities surrounding these issues, especially for younger individuals facing difficult decisions about the timing of genetic testing, family planning, and the potential use of assisted reproductive options.

Development of pancreatic diseases during long-term follow-up after acute pancreatitis: a post-hoc analysis of a prospective multicenter cohort.

BACKGROUND AND AIM: More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling. METHODS: A long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed. RESULTS: Overall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP. CONCLUSION: Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.

Risk factors for a permanent stoma after resection of left-sided obstructive colon cancer - A prediction model.

INTRODUCTION: In patients with left-sided obstructive colon cancer (LSOCC), a stoma is often constructed as part of primary treatment, but with a considerable risk of becoming a permanent stoma (PS). The aim of this retrospective multicentre cohort is to identify risk factors for a PS in LSOCC and to develop a pre- and postoperative prediction model for PS. MATERIALS AND METHODS: Data was retrospectively obtained from 75 hospitals in the Netherlands. Patients who had curative resection of LSOCC between January 1, 2009 to December 31, 2016 were included with a minimum follow-up of 6 months after resection. The interventions analysed were emergency resection, decompressing stoma or stent as bridge-to-elective resection. Main outcome measure was presence of PS at the end of follow-up. Multivariable logistic regression analysis was performed to identify risk factors for PS at primary presentation (T0) and after resection, in patients having a stoma in situ (T1). These risk factors were used to construct a web-based prediction tool. RESULTS: Of 2099 patients included in the study (T0), 779 had a PS (37%). A total of 1275 patients had a stoma in situ directly after resection (T1), of whom 674 had a PS (53%). Median follow-up was 34 months. Multivariable analysis showed that older patients, female sex, high ASA-score and open approach were independent predictors for PS in both the T0 and T1 population. Other predictors at T0 were sigmoid location, low Hb, high CRP, cM1 stage, and emergency resection. At T1, subtotal colectomy, no primary anastomosis, not receiving adjuvant chemotherapy and high pTNM stage were additional predictors. Two predictive models were built, with an AUC of 0.74 for T0 and an AUC of 0.81 for T1. CONCLUSIONS: PS is seen in 37% of the patients who have resection of LSOCC. In patients with a stoma in situ directly after resection, 53% PS are seen due to non-reversal. Not only baseline characteristics, but also treatment strategies determine the risk of a PS in patients with LSOCC. The developed predictive models will give physicians insight in the role of the individual variables on the risk of a PS and help in informing the patient about the probability of a PS.

[Pancreatic cystic neoplasms: a clinical dilemma]. / Neoplastische cysten van het pancreas.

Pancreatic cystic neoplasms are increasingly detected in the general population. Although most of these lesions are benign, some are (pre)malignant and require follow-up or even surgical intervention. Three cases are presented and used to discuss the clinical implications of the renewed European Guideline on pancreatic cystic neoplasms in which relative and absolute indications for resection are proposed. In the first case, a pancreatic cystic lesion was found on abdominal ultrasound in a 77-year old female patient. After endoscopic ultrasound was performed, a serous cystic neoplasm was diagnosed without need for surveillance. In a 57-year old male, an abdominal MRI was performed to further assess an incidentally found pancreatic cystic lesion. Based on the MRI, a side-branch intraductal papillary mucinous neoplasm (SB-IPMN) was diagnosed and yearly surveillance was initiated. A 61-year old male underwent a laparoscopic distal pancreatectomy because of a mixed-type IPMN (MT-IPMN). The pathological results showed an IPMN with high-grade dysplasia.

Recurrence of idiopathic acute pancreatitis after cholecystectomy: systematic review and meta-analysis.

BACKGROUND: Occult biliary disease has been suggested as a frequent underlying cause of idiopathic acute pancreatitis (IAP). Cholecystectomy has been proposed as a strategy to prevent recurrent IAP. The aim of this systematic review was to determine the efficacy of cholecystectomy in reducing the risk of recurrent IAP. METHODS: PubMed, Embase and Cochrane Library databases were searched systematically for studies including patients with IAP treated by cholecystectomy, with data on recurrence of pancreatitis. Studies published before 1980 or including chronic pancreatitis and case reports were excluded. The primary outcome was recurrence rate. Quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses were undertaken to calculate risk ratios using a random-effects model with the inverse-variance method. RESULTS: Overall, ten studies were included, of which nine were used in pooled analyses. The study population consisted of 524 patients with 126 cholecystectomies. Of these 524 patients, 154 (29·4 (95 per cent c.i. 25·5 to 33·3) per cent) had recurrent disease. The recurrence rate was significantly lower after cholecystectomy than after conservative management (14 of 126 (11·1 per cent) versus 140 of 398 (35·2 per cent); risk ratio 0·44, 95 per cent c.i. 0·27 to 0·71). Even in patients in whom IAP was diagnosed after more extensive diagnostic testing, including endoscopic ultrasonography or magnetic resonance cholangiopancreatography, the recurrence rate appeared to be lower after cholecystectomy (4 of 36 (11 per cent) versus 42 of 108 (38·9 per cent); risk ratio 0·41, 0·16 to 1·07). CONCLUSION: Cholecystectomy after an episode of IAP reduces the risk of recurrent pancreatitis. This implies that current diagnostics are insufficient to exclude a biliary cause.

ANTECEDENTES: Se ha sugerido que la enfermedad biliar oculta es una causa subyacente frecuente de pancreatitis aguda idiopática (idiopathic acute pancreatitis, IAP). La colecistectomía se ha propuesto como una estrategia para prevenir la IAP recidivante. El objetivo de esta revisión sistemática era determinar la eficacia de la colecistectomía para reducir el riesgo de la IAP recidivante. MÉTODOS: Se realizó una búsqueda sistemática en PubMed, Embase y Cochrane de estudios que incluían pacientes con IAP tratados con colecistectomía, y con datos sobre la recidiva de la pancreatitis. Se excluyeron los estudios anteriores a 1980, los que incluían pancreatitis crónica y los casos clínicos. El resultado principal fue la tasa de recidiva. La calidad se evaluó utilizando la escala de Newcastle-Ottawa. Se realizaron metaanálisis para calcular la tasa de riesgo utilizando un modelo de efectos aleatorios con el método de varianza inversa. RESULTADOS: En total, se incluyeron 10 estudios, de los cuales 9 se utilizaron para realizar análisis agrupados. La población de estudio incluyó 524 pacientes en los que se habían efectuado 126 colecistectomías. De estos 524 pacientes, 154 (29% (i.c. del 95% 25,5-33,3)) presentaron recidiva de la enfermedad. La tasa de recidiva fue significativamente menor después de la colecistectomía que después del tratamiento conservador (14/126 (11%) versus 140/398 (35)); tasa de riesgo 0,44 (i.c. del 95% 0,27-0,71)). Incluso en pacientes en los que se diagnosticó IAP tras haber efectuado pruebas diagnósticas más extensas, incluyendo ultrasonografía endoscópica o colangiopancreatografía por resonancia magnética, la tasa de recidiva después de la colecistectomía era menor (4/36 (11%) versus 42/108 (39%); tasa de riesgo 0,41 (i.c. del 95% 0,16-1,07)). CONCLUSIÓN: La práctica de una colecistectomía después de un episodio de IAP disminuye el riesgo de pancreatitis recidivante. Esto implica que los diagnósticos actuales son insuficientes para excluir una causa biliar (PROSPERO CRD42017055275).

Surveillance for pancreatic cancer in high-risk individuals.

Background: Surveillance of individuals at high risk of pancreatic ductal adenocarcinoma (PDAC) and its precursors might lead to better outcomes. The aim of this study was to determine the prevalence and outcomes of PDAC and high-risk neoplastic precursor lesions among such patients participating in surveillance programmes. Methods: A multicentre study was conducted through the International CAncer of the Pancreas Screening (CAPS) Consortium Registry to identify high-risk individuals who had undergone pancreatic resection or progressed to advanced PDAC while under surveillance. High-risk neoplastic precursor lesions were defined as: pancreatic intraepithelial neoplasia (PanIN) 3, intraductal papillary mucinous neoplasia (IPMN) with high-grade dysplasia, and pancreatic neuroendocrine tumours at least 2 cm in diameter. Results: Of 76 high-risk individuals identified in 11 surveillance programmes, 71 had undergone surgery and five had been diagnosed with inoperable PDAC. Of the 71 patients who underwent resection, 32 (45 per cent) had PDAC or a high-risk precursor (19 PDAC, 4 main-duct IPMN, 4 branch-duct IPMN, 5 PanIN-3); the other 39 patients had lesions thought to be associated with a lower risk of neoplastic progression. Age at least 65 years, female sex, carriage of a gene mutation and location of a lesion in the head/uncinate region were associated with high-risk precursor lesions or PDAC. The survival of high-risk individuals with low-risk neoplastic lesions did not differ from that in those with high-risk precursor lesions. Survival was worse among patients with PDAC. There was no surgery-related mortality. Conclusion: A high proportion of high-risk individuals who had surgical resection for screening- or surveillance-detected pancreatic lesions had a high-risk neoplastic precursor lesion or PDAC at the time of surgery. Survival was better in high-risk individuals who had either low- or high-risk neoplastic precursor lesions compared with that in patients who developed PDAC.

Antecedentes: Se podrían obtener mejores resultados con el seguimiento de individuos de alto riesgo para adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) y lesiones precursoras. El objetivo de este estudio fue determinar la prevalencia y los resultados del PDAC y de las lesiones precursoras de alto riesgo neoplásico en pacientes que participaron en programas de seguimiento. Métodos: Se llevó a cabo un estudio multicéntrico a través del registro internacional del consorcio CAPS (Common Automotive Platform Standard) para identificar a las personas de alto riesgo que se habían sometido a una resección pancreática o habían progresado a PDAC avanzado mientras estaban en seguimiento. Se definieron como lesiones neoplásicas precursoras de alto riesgo la neoplasia intraepitelial pancreática de tipo 3 (PanIN­3), la neoplasia papilar mucinosa intraductal (intraductal papillary mucinous neoplasia, IPMN) con displasia de alto grado y los tumores neuroendocrinos pancreáticos (pancreatic neuroendocrine tumours, PanNET) de ≥ 2 cm de diámetro. Resultados: De 76 individuos con lesiones de alto riesgo identificados en 11 programas de seguimiento, 71 fueron tratados quirúrgicamente y 5 fueron diagnosticados de un PDAC inoperable. De las 71 resecciones, 32 (45%) tenían PDAC o una lesión precursora de alto riesgo (19 PDAC, 4 IPMN de conducto principal, 4 IPMN de rama secundaria y 5 PanIN­3). Los otros 39 pacientes tenían lesiones que se consideraron asociadas con un menor riesgo de progresión neoplásica. La edad ≥ 65 años, el sexo femenino, el ser portador de una mutación genética y la localización de la lesión en la cabeza/proceso uncinado fueron factores asociados a las lesiones precursoras de alto riesgo o al PDAC. No hubo diferencias en la supervivencia de individuos de alto riesgo con lesiones neoplásicas de bajo riesgo frente a aquellos que presentaron lesiones precursoras de alto riesgo. La supervivencia fue peor en los pacientes con PDAC. No hubo mortalidad relacionada con la cirugía. Conclusión: Un elevado porcentaje de individuos de alto riesgo que se sometieron a resección quirúrgica tras la detección de lesiones pancreáticas en el seguimiento tenían una lesión precursora neoplásica de alto riesgo o un PDAC. La supervivencia fue mejor en individuos de alto riesgo que tenían lesiones precursoras neoplásicas de bajo o alto riesgo en comparación con aquellos pacientes que habían desarrollado un PDAC.

Propensity score-matched analysis of oncological outcome between stent as bridge to surgery and emergency resection in patients with malignant left-sided colonic obstruction.

BACKGROUND: Although self-expandable metal stent (SEMS) placement as bridge to surgery (BTS) in patients with left-sided obstructing colonic cancer has shown promising short-term results, it is used infrequently owing to uncertainty about its oncological safety. This population study compared long-term oncological outcomes between emergency resection and SEMS placement as BTS. METHODS: Through a national collaborative research project, long-term outcome data were collected for all patients who underwent resection for left-sided obstructing colonic cancer between 2009 and 2016 in 75 Dutch hospitals. Patients were identified from the Dutch Colorectal Audit database. SEMS as BTS was compared with emergency resection in the curative setting after 1 : 2 propensity score matching. RESULTS: Some 222 patients who had a stent placed were matched to 444 who underwent emergency resection. The overall SEMS-related perforation rate was 7·7 per cent (17 of 222). Three-year locoregional recurrence rates after SEMS insertion and emergency resection were 11·4 and 13·6 per cent (P = 0·457), disease-free survival rates were 58·8 and 52·6 per cent (P = 0·175), and overall survival rates were 74·0 and 68·3 per cent (P = 0·231), respectively. SEMS placement resulted in significantly fewer permanent stomas (23·9 versus 45·3 per cent; P < 0·001), especially in elderly patients (29·0 versus 57·9 per cent; P < 0·001). For patients in the SEMS group with or without perforation, 3-year locoregional recurrence rates were 18 and 11·0 per cent (P = 0·432), disease-free survival rates were 49 and 59·6 per cent (P = 0·717), and overall survival rates 61 and 75·1 per cent (P = 0·529), respectively. CONCLUSION: Overall, SEMS as BTS seems an oncologically safe alternative to emergency resection with fewer permanent stomas. Nevertheless, the risk of SEMS-related perforation, as well as permanent stoma, might influence shared decision-making for individual patients.

Treatment of refractory post-esophagectomy anastomotic esophageal strictures using temporary fully covered esophageal metal stenting compared to repeated bougie dilation: results of a randomized controlled trial.

Background and study aims Fully covered self-expanding metal stents (FCSEMS) provide an alternative to bougie dilation (BD) for refractory benign esophageal strictures. Controlled studies comparing temporary placement of FCSES to repeated BD are not available. Patients and methods Patients with refractory anastomotic esophageal strictures, dysphagia scores ≥ 2, and two to five prior BD were randomized to 8 weeks of FCSEMS or to repeated BD. The primary endpoint was the number of BD during the 12 months after baseline treatment. Results Eighteen patients were included (male 67 %, median age 66.5; 9 received metal stents, 9 received BD). Technical success rate of stent placement and stent removal was 100 %. Recurrent dysphagia occurred in 13 patients (72 %) during follow-up. No significant difference was found between the stent and BD groups for mean number of BD during follow-up (5.4 vs. 2.4, P  = 0.159), time to recurrent dysphagia (median 36 days vs. 33 days, Kaplan-Meier: P  = 0.576) and frequency of reinterventions per month (median 0.3 vs. 0.2, P  = 0.283). Improvement in quality of life score was greater in the stent group compared to the BD group at month 12 (median 26 % vs. 4 %, P  = 0.011). Conclusions The current data did not provide evidence for a statistically significant difference between the two groups in the number of BD during the 12 months after initial treatment. Metal stenting offers greater improvement in quality of life from baseline at 12 months compared to repeated BD for patients with refractory anastomotic esophageal strictures.

Modern work-up and extended resection in perihilar cholangiocarcinoma: the AMC experience.

AIM: Perihilar cholangiocarcinoma (PHC) is a challenging disease and requires aggressive surgical treatment in order to achieve curation. The assessment and work-up of patients with presumed PHC is multidisciplinary, complex and requires extensive experience. The aim of this paper is to review current aspects of diagnosis, preoperative work-up and extended resection in patients with PHC from the perspective of our own institutional experience with this complex tumor. METHODS: We provided a review of applied modalities in the diagnosis and work-up of PHC according to current literature. All patients with presumed PHC in our center between 2000 and 2016 were identified and described. The types of resection, surgical techniques and outcomes were analyzed. RESULTS AND CONCLUSION: Upcoming diagnostic modalities such as Spyglass and combinations of serum biomarkers and molecular markers have potential to decrease the rate of misdiagnosis of benign, inflammatory disease. Assessment of liver function with hepatobiliary scintigraphy provides better information on the future remnant liver (FRL) than volume alone. The selective use of staging laparoscopy is advisable to avoid futile laparotomies. In patients requiring extended resection, selective preoperative biliary drainage is mandatory in cholangitis and when FRL is small (< 50%). Preoperative portal vein embolization (PVE) is used when FRL volume is less than 40% and optionally includes the left portal vein branches to segment 4. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as alternative to PVE is not recommended in PHC. N2 positive lymph nodes preclude long-term survival. The benefit of unconditional en bloc resection of the portal vein bifurcation is uncertain. Along these lines, an aggressive surgical approach encompassing extended liver resection including segment 1, regional lymphadenectomy and conditional portal venous resection translates into favorable long-term survival.

[Multidisciplinary treatment of chronic pancreatitis: an overview of current step-up approach and new options]. / Multidisciplinaire behandeling van chronische pancreatitis.

- Chronic pancreatitis is a progressive inflammatory disease, which leads to a severe decrease in quality of life and reduced life expectancy.- 85-90% of patients with chronic pancreatitis consult the doctor because of pain.- Pain in chronic pancreatitis has a multifactorial aetiology, with nociceptive and neuropathological components.- Current treatment of chronic pancreatitis uses a step-up approach, starting with lifestyle interventions and medication, followed by endoscopic or surgical treatment or a combination of these two.- Surgical drainage or resection is more effective than repeated endoscopic treatment for patients with advanced chronic pancreatitis who use opiates.- There are indications that early surgical intervention in painful chronic pancreatitis and a dilated pancreatic duct provides better results than the current step-up approach; this is currently being investigated in the ESCAPE trial.

Systematic review and meta-analysis on the prevalence of vitamin D deficiency in patients with chronic pancreatitis.

BACKGROUND/OBJECTIVES: Patients with chronic pancreatitis (CP) are at risk of malnutrition due to malabsorption, pain and/or alcohol consumption. This can cause vitamin D insufficiency or deficiency, which is associated with osteoporosis and increased risks of fractures. We aimed to perform a meta-analysis to determine the prevalence of vitamin D insufficiency and deficiency in CP patients. Furthermore, we compared these results with healthy controls. METHODS: We performed a systematic review and meta-analysis on the literature by searching PubMed and EMBASE (January 2000-December 2015) on CP and vitamin D. Primary outcome was prevalence of vitamin D insufficiency (<75 nmoL/L) and deficiency (<50 nmoL/L) in CP patients. When available, data of CP patients were compared with healthy controls. RESULTS: Nine studies were included in our meta-analysis, reporting on the prevalence of vitamin D insufficiency/deficiency in 465 patients (mean age 41 years (range 18-60), 81% male) and in 378 controls (mean age 40 years (range 18-67), 76% male). Pooled prevalence of vitamin D insufficiency and deficiency in CP patients was 83% and 65%, respectively. Calculated odds ratio (OR) of vitamin D insufficiency and deficiency between CP patients and controls was 1.34 (0.54-3.29) and 1.14 (0.70-1.85), respectively (p > 0.05). CONCLUSION: There is a high prevalence of vitamin D insufficiency and deficiency in CP patients. Nevertheless, there is no significant difference in prevalence of vitamin D insufficiency and deficiency compared to healthy controls. Further research should indicate the clinical relevance and consequences of these findings for clinical practice.

Metal or plastic stents for preoperative biliary drainage in resectable pancreatic cancer.

INTRODUCTION: In pancreatic cancer, preoperative biliary drainage (PBD) increases complications compared with surgery without PBD, demonstrated by a recent randomised controlled trial (RCT). This outcome might be related to the plastic endoprosthesis used. Metal stents may reduce the PBD-related complications risk. METHODS: A prospective multicentre cohort study was performed including patients with obstructive jaundice due to pancreatic cancer, scheduled to undergo PBD before surgery. This cohort was added to the earlier RCT (ISRCTN31939699). The RCT protocol was adhered to, except PBD was performed with a fully covered self-expandable metal stent (FCSEMS). This FCSEMS cohort was compared with the RCT's plastic stent cohort. PBD-related complications were the primary outcome. Three-group comparison of overall complications including early surgery patients was performed. RESULTS: 53 patients underwent PBD with FCSEMS compared with 102 patients treated with plastic stents. Patients' characteristics did not differ. PBD-related complication rates were 24% in the FCSEMS group vs 46% in the plastic stent group (relative risk of plastic stent use 1.9, 95% CI 1.1 to 3.2, p=0.011). Stent-related complications (occlusion and exchange) were 6% vs 31%. Surgical complications did not differ, 40% vs 47%. Overall complication rates for the FCSEMS, plastic stent and early surgery groups were 51% vs 74% vs 39%. CONCLUSIONS: For PBD in pancreatic cancer, FCSEMS yield a better outcome compared with plastic stents. Although early surgery without PBD remains the treatment of choice, FCSEMS should be preferred over plastic stents whenever PBD is indicated. TRIAL REGISTRATION NUMBER: Dutch Trial Registry (NTR3142).

Safety and efficacy of a fully covered large-diameter self-expanding metal stent for the treatment of upper gastrointestinal perforations, anastomotic leaks, and fistula.

Upper gastrointestinal perforations, fistula, and anastomotic leaks are severe conditions with high mortality. Temporary endoscopic placement of fully covered self-expanding metal stent (fSEMS) has emerged as treatment option. Stent migration is a major drawback of currently used stents. Migration is often attributed to a relatively too small stent diameter as esophageal stents were initially intended for the treatment of strictures. This study aimed to investigate the safety and efficacy of a large-diameter fSEMS for treatment of these conditions. Data were retrospectively collected from patients who received this stent in the Netherlands between March 2011 and August 2013. Clinical success was defined as sufficient leak closure after stent removal as confirmed by endoscopy or X-ray with oral contrast without surgical intervention or placement of another type of stent. Adverse events were graded according a standardized grading system. Stent placement was performed in 34 patients for the following indications: perforation (n = 6), anastomotic leak (n = 26), and fistula (n = 2). Technical success rate was 97% (33/34). Clinical success rate was 44% (15/34) after one stent and 50% (17/34) after an additional stent. There were no severe adverse events and stent-related mortality. The overall adverse event rate was 50% (all graded 'moderate'). There were 14 (41%) stent migrations (complete n = 8, partial n = 6). Other adverse events were bleeding (n = 2) and aspiration pneumonia (n = 1). Reinterventions for failure of the large-diameter fSEMS were placement of another type of fSEMS (n = 4), surgical repair (n = 3), or esophagectomy (n = 1). Eleven patients (32%) died in-hospital because of persisting intrathoracic sepsis (n = 10) or preexistent bowel ischemia (n = 1). This study suggests that temporary placement of a large-diameter fSEMS for the treatment of upper gastrointestinal perforations, fistula, and anastomotic leaks is safe in terms of severe adverse events and stent-related mortality. The larger diameter does not seem to prevent stent migration.

A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals.

OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI. DESIGN: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10 mm. Results were compared in a blinded, independent fashion. RESULTS: Two solid lesions (mean size 9 mm) and nine cysts ≥10 mm (mean size 17 mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10 mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size. CONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.

Long-term results of palliative stent placement for acute malignant colonic obstruction.

BACKGROUND: Endoscopic placement of self-expanding-metal-stents (SEMS) is widely performed as palliative treatment for acute malignant colonic obstruction. There is ongoing debate regarding risks and benefits associated with SEMS placement. This study aimed to evaluate long-term outcomes of palliative SEMS placement in patients presenting with acute malignant colonic obstruction. METHODS: A prospectively collected patient cohort (2005-2013) from a general teaching hospital was used. In this hospital, all consecutive patients presenting with acute malignant large bowel obstruction are treated with endoscopic SEMS placement. Only colon cancer patients who underwent palliative SEMS placement were selected. RESULTS: In total, 48 patients were included. The technical and short-term clinical success rates were 91 % (44/48) and 85 % (36/48), respectively. SEMS-related mortality occurred in 6/48 patients (13 %) (early n = 4, late n = 2) and was caused by SEMS-related perforation in all cases. The SEMS-related morbidity rate was 38 % (18/48) (early n = 7, late n = 11). Endoscopic re-intervention was performed 14 times and 13 patients eventually underwent surgical treatment during follow-up. The stoma-formation rate was 15 % (7/48). Long-term clinical success was 48 % (23/48). The estimated stent patency rate (95 % confidence interval) was 69 % (52-79) at 1 month, 54 % (37-66) at 6 months and 50 % (33-62) at 12 months. CONCLUSION: Palliative SEMS placement provides rapid relief of obstruction and avoids a stoma in most patients with acute colonic obstruction caused by incurable or inoperable colon cancer. However, these benefits should be weighed against mortality and morbidity related to SEMS placement.

Dutch Chronic Pancreatitis Registry (CARE): design and rationale of a nationwide prospective evaluation and follow-up.

BACKGROUND: Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted. METHODS: The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years. RESULTS: A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years. DISCUSSION: The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies.

Definitive chemoradiation for patients with inoperable and/or unresectable esophageal cancer: locoregional recurrence pattern.

A locoregional recurrence after definitive chemoradiation (dCRT) for patients with inoperable or unresectable esophageal cancer occurs in about 50% of the patients and is a major cause of failure with a poor prognosis. The aim of this study was to determine the pattern of locoregional recurrence and its prognostic factors after dCRT in order to search for improvements in radiation treatment. We retrospectively reviewed 184 patients treated with external beam radiotherapy (50.4 Gray/28 fractions), combined with weekly concurrent paclitaxel and carboplatin. Locoregional recurrences were defined by clinical signs of recurrent or progressive disease, combined with progression on computed tomography/positron emission tomography-computed tomography scan, or suspicious endoscopic findings and/or histological proof of recurrence. The site of locoregional recurrence was analyzed with respect to the borders of the radiation fields. After a mean follow up of 22.8 months, 76 patients (41%) had evidence of locoregional recurrence. The 3-years locoregional recurrence-free rate was 45%. The majority of locoregional recurrences occurred within 12 months, nearly all within 24 months. The majority of these patients failed at the site of the primary tumor (86%). Infield locoregional recurrences at the site of the lymph nodes only occurred in 1% compared with 57% at the site of the primary tumor only. Outfield locoregional lymph node recurrences occurred in 22%, without infield recurrence occurred in only 4% of all patients. The 1-, 3-, and 5-year overall survival was 65%, 28%, and 21%, respectively. The current analysis demonstrates that a locoregional recurrence after dCRT occurs in 41% of the patients, the majority at the site of the primary tumor. These data suggest a benefit of dose intensification of the primary tumor, but not at the site of the lymph nodes. Higher radiation doses should be assessed with prospective trials.

Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). This Guideline was also reviewed and endorsed by the Governing Board of the American Society for Gastrointestinal Endoscopy (ASGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations The following recommendations should only be applied after a thorough diagnostic evaluation including a contrast-enhanced computed tomography (CT) scan. 1 Prophylactic colonic stent placement is not recommended. Colonic stenting should be reserved for patients with clinical symptoms and imaging evidence of malignant large-bowel obstruction, without signs of perforation (strong recommendation, low quality evidence). 2 Colonic self-expandable metal stent (SEMS) placement as a bridge to elective surgery is not recommended as a standard treatment of symptomatic left-sided malignant colonic obstruction (strong recommendation, high quality evidence). 3 For patients with potentially curable but obstructing left-sided colonic cancer, stent placement may be considered as an alternative to emergency surgery in those who have an increased risk of postoperative mortality, I. e. American Society of Anesthesiologists (ASA) Physical Status ≥ III and/or age > 70 years (weak recommendation, low quality evidence). 4 SEMS placement is recommended as the preferred treatment for palliation of malignant colonic obstruction (strong recommendation, high quality evidence), except in patients treated or considered for treatment with antiangiogenic drugs (e. g. bevacizumab) (strong recommendation, low quality evidence).(AU)