Outcomes of Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma in the Netherlands: A Nationwide Retrospective Analysis

Background: Large multicenter series on outcomes and predictors of survival after distal pancreatectomy (DP) for pancreatic ductal adenocarcinoma (PDAC) are scarce. Methods: Adults who underwent DP for PDAC in 17 Dutch pancreatic centers between January 2005 and September 2013 were analyzed retrospectively. The primary outcome was survival, and predictors of survival were identified using Cox regression analysis. Results: In total, 761 consecutive patients after DP were assessed, of whom 620 patients were excluded because of non-PDAC histopathology (n = 616) or a lack of data (n = 4), leaving a total of 141 patients included in the stud

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

Minimally invasive versus open distal pancreatectomy (LEOPARD): Study protocol for a randomized controlled trial

Background: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. Methods: LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. Discussion: The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. Trial registration: Dutch Trial Register, NTR5188. Registered on 9 April 201

Outcome of pancreatic surgery during the first 6 years of a mandatory audit within the Dutch Pancreatic Cancer Group

Objective:To describe outcome after pancreatic surgery in the first 6 years of a mandatory nationwide audit. Background:Within the Dutch Pancreatic Cancer Group, efforts have been made to improve outcome after pancreatic surgery. These include collaborative projects, clinical auditing, and implementation of an algorithm for early recognition and management of postoperative complications. However, nationwide changes in outcome over time have not yet been described. Methods:This nationwide cohort study included consecutive patients after pancreatoduodenectomy (PD) and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014-December 2019). Patient, tumor, and treatment characteristics were compared between 3 time periods (2014-2015, 2016-2017, and 2018-2019). Short-term surgical outcome was investigated using multilevel multivariable logistic regression analyses. Primary endpoints were failure to rescue (FTR) and in-hospital mortality. Results:Overall, 5345 patients were included, of whom 4227 after PD and 1118 after distal pancreatectomy. After PD, FTR improved from 13% to 7.4% [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50-0.80, P75 years (18%-22%, P=0.006), American Society of Anesthesiologists score & GE;3 (19%-31%, P<0.001) and Charlson comorbidity score & GE;2 (24%-34%, P<0.001). The rates of textbook outcome (57%-55%, P=0.283) and major complications remained stable (31%-33%, P=0.207), whereas complication-related intensive care admission decreased (13%-9%, P=0.002). After distal pancreatectomy, improvements in FTR from 8.8% to 5.9% (OR 0.65, 95% CI 0.30-1.37, P=0.253) and in-hospital mortality from 1.6% to 1.3% (OR 0.88, 95% CI 0.45-1.72, P=0.711) were not statistically significant. Conclusions:During the first 6 years of a nationwide audit, in-hospital mortality and FTR after PD improved despite operating on more high-risk patients. Several collaborative efforts may have contributed to these improvements.Surgical oncolog

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Der Toten gedenken: Eine kultursoziologische Analyse von Friedhöfen und Grabsteinen

Erst im 19. Jahrhundert setzte sich die Idee durch, dass jede Einzelperson das Recht zu ihrem eigenen dauerhaften Grab habe. Vor diesem historischen Hintergrund analysieren wir die individualisierten Sinngebungsformen, die in den letzten Jahrzehnten des 20. Jahrhunderts auf den Friedhöfen an Bedeutung gewonnen haben. Wir besprechen drei zentrale Sinngebungsaspekte dieser Gedächtnisorte: die Steigerung der Individualisierung und die Akzentuierung der Individualität der Verstorbenen (a), die Steigerung der Bewertung des diesseitigen, verkörperten Lebens (b), sowie Umwandlungen in den Formen und in der Sichtbarkeit der relevanten Sozialnetzwerke (c). Auf den Friedhöfen wird eine Welt geschaffen, die auf die individuelle Eigenheit ihrer ,Bewohner‘ abgestellt ist und sich durch diese organisiert, und zwar ganz unbeschadet der Tatsache, dass die Figuren als Typen gemeint sind – die sich in der Realität oft wiederholen mögen. Abstract Until the nineteenth century, most people did not inter their dead in individual tombs or construct permanent graves. Against this historical background, we analyze the individualized forms of meaning that have gained importance at public cemeteries since the last decades of the twentieth century. We identify and analyze three evolutions: (a) the construction of idiosyncratic markers and the accompanying emergence of individualized identities (b) the increasing emphasis on embodied identities, and (c) the increasing visibility of voluntary social commitments and strong ties. Markers to the dead are markers of individuality. They now reflect a growing concern with, and commitment to, incomparable identities and individualized memories – even if the selected forms are often duplicated in reality

Pancreatoduodenectomy with colon resection for cancer: A nationwide retrospective analysis

Microscopically radical (R0) resection of pancreatic, periampullary, or colon cancer may occasionally require a pancreatoduodenectomy with colon resection (PD-colon), but the benefits of this procedure have been disputed, and multicenter studies on morbidity and oncologic outcomes after PD-colon are lacking. This study aimed to assess complications and survival after PD-colon. Patients who had undergone PD-colon from 2004-2014 in 1 of 13 centers were analyzed retrospectively. Ninety-day morbidity was scored using the Clavien-Dindo score and the Comprehensive Complication Index (CCI, 0 = no complications, 100 = death). Survival was analyzed per histopathologic diagnosis. After screening 3,218 consecutive PDs, 50 (1.6%) PD-colon patients (median age 66 years [interquartile range 55-72], 33 [66%] men) were included. Twenty-three (46%) patients had pancreatic ductal adenocarcinoma (PDAC), 19 (38%) other pathology, and 8 (16%) colon cancer. Ninety-day Clavien-Dindo ≥3 complications occurred in 30 (60%) patients without differences per diagnosis (P > .99); mean CCI was 39 (standard deviation 27). Colonic anastomosis leak, pancreatic fistula, and 90-day mortality occurred in 3 (6%), 2 (4%), and 4 (8%) patients, respectively. A total of 11/23 (48%) patients with PDAC and 8/8 (100%) patients with colon cancer underwent an R0 resection. Patients with PDAC had a median postoperative survival of 13 months (95% confidence interval = 5-21). One-, 3-, and 5-year cumulative survival was 56%, 21%, and 14%, respectively. Median survival after R0 resection for PDAC was 21 months (95% confidence interval = 6-35). All patients with colon cancer were alive at end of follow-up (median 24 months [95% confidence interval = 9-110]). In this retrospective, multicenter study, PD-colon was associated with considerable complications and acceptable survival rates when a tumor negative resection margin was achieve

Minimally invasive versus open distal pancreatectomy (LEOPARD): study protocol for a randomized controlled trial

Contains fulltext : 175625.pdf (publisher's version ) (Open Access)BACKGROUND: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. METHODS: LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. DISCUSSION: The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. TRIAL REGISTRATION: Dutch Trial Register, NTR5188 . Registered on 9 April 2015