Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): study protocol for an international multicentre prospective diagnostic accuracy study.

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.

Primary intra-articular epithelioid sarcoma of the knee: Unusual presentation of a rare entity.

We report a case of a 60-year-old female with severe and progressive pain of her right knee. Physical therapy, pain medication, and arthroscopic debridement were unsuccessful. Finally, pathological examination revealed an intra-articular epithelioid sarcoma, a rare tumor in an atypical location. Patient died within 5 months after initial admission. Despite this unusual clinical course and presentation, we would like to share the valuable clinical lessons we learned from this case. Introduction of a coordinating physician in combination with a multidisciplinary treatment regarding optimal pain management should optimize treatment results in future patients.

The association between portal system vein diameters and outcomes in acute pancreatitis.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) progresses to necrotizing pancreatitis in 15% of cases. An important pathophysiological mechanism in AP is third spacing of fluids, which leads to intravascular volume depletion. This results in a reduced splanchnic circulation and reduced venous return. Non-visualisation of the portal and splenic vein on early computed tomography (CT) scan, which might be the result of smaller vein diameter due to decreased venous flow, is associated with infected necrosis and mortality in AP. This observation led us to hypothesize that smaller diameters of portal system veins (portal, splenic and superior mesenteric) are associated with increased severity of AP. METHODS: We conducted a post-hoc analysis of data from two randomized controlled trials that included patients with predicted severe and mild AP. The primary endpoint was AP-related mortality. The secondary endpoints were (infected) necrotizing pancreatitis and (persistent) organ failure. We performed additional CT measurements of portal system vein diameters and calculated their prognostic value through univariate and multivariate Poisson regression. RESULTS: Multivariate regression showed a significant inverse association between splenic vein diameter and mortality (RR 0.75 (0.59-0.97)). Furthermore, there was a significant inverse association between splenic and superior mesenteric vein diameter and (infected) necrosis. Diameters of all veins were inversely associated with organ failure and persistent organ failure. CONCLUSIONS: We observed an inverse relationship between portal system vein diameter and morbidity and an inverse relationship between splenic vein diameter and mortality in AP. Further research is needed to test whether these results can be implemented in predictive scoring systems.

Nationwide outcomes in patients undergoing surgical exploration without resection for pancreatic cancer.

BACKGROUND: Despite improvements in diagnostic imaging and staging, unresectable pancreatic cancer is still encountered during surgical exploration with curative intent. This nationwide study investigated outcomes in patients with unresectable pancreatic cancer found during surgical exploration. METHODS: All patients diagnosed with primary pancreatic (adeno)carcinoma (2009-2013) in the Netherlands Cancer Registry were included. Predictors of unresectability, 30-day mortality and poor survival were evaluated using logistic and Cox proportional hazards regression analysis. RESULTS: There were 10 595 patients with pancreatic cancer during the study interval. The proportion of patients undergoing surgical exploration increased from 19·9 to 27·0 per cent (P < 0·001). Among 2356 patients who underwent surgical exploration, the proportion of patients with tumour resection increased from 61·6 per cent in 2009 to 71·3 per cent in 2013 (P < 0·001), whereas the contribution of M1 disease (18·5 per cent overall) remained stable. Patients who had exploration only had an increased 30-day mortality rate compared with those who underwent tumour resection (7·8 versus 3·8 per cent; P < 0·001). In the non-resected group, among those with M0 (383 patients) and M1 (435) disease at surgical exploration, the 30-day mortality rate was 4·7 and 10·6 per cent (P = 0·002), median survival was 7·2 and 4·4 months (P < 0·001), and 1-year survival rates were 28·0 and 12·9 per cent, respectively. Among other factors, low hospital volume (0-20 resections per year) was an independent predictor for not undergoing tumour resection, but also for 30-day mortality and poor survival among patients without tumour resection. CONCLUSION: Exploration and resection rates increased, but one-third of patients who had surgical exploration for pancreatic cancer did not undergo resection. Non-resectional surgery doubled the 30-day mortality rate compared with that in patients undergoing tumour resection.

Diagnostic performance of imaging modalities in chronic pancreatitis: a systematic review and meta-analysis.

OBJECTIVES: Obtain summary estimates of sensitivity and specificity for imaging modalities for chronic pancreatitis (CP) assessment. METHODS: A systematic search was performed in Cochrane Library, MEDLINE, Embase and CINAHL databases for studies evaluating imaging modalities for the diagnosis of CP up to September 2016. A bivariate random-effects modeling was used to obtain summary estimates of sensitivity and specificity. RESULTS: We included 43 studies evaluating 3460 patients. Sensitivity of endoscopic retrograde cholangiopancreatography (ERCP) (82%; 95%CI: 76%-87%) was significant higher than that of abdominal ultrasonography (US) (67%; 95%CI: 53%-78%; P=0.018). The sensitivity estimates of endoscopic ultrasonography (EUS), magnetic resonance imaging (MRI), and computed tomography (CT) were 81% (95%CI: 70%-89%), 78% (95%CI: 69%-85%), and 75% (95%CI: 66%-83%), respectively, and did not differ significantly from each other. Estimates of specificity were comparable for EUS (90%; 95%CI: 82%-95%), ERCP (94%; 95%CI: 87%-98%), CT (91%; 95% CI: 81%-96%), MRI (96%; 95%CI: 90%-98%), and US (98%; 95%CI: 89%-100%). CONCLUSIONS: EUS, ERCP, MRI and CT all have comparable high diagnostic accuracy in the initial diagnosis of CP. EUS and ERCP are outperformers and US has the lowest accuracy. The choice of imaging modality can therefore be made based on invasiveness, local availability, experience and costs. KEY POINTS: • EUS, ERCP, MRI and CT have high diagnostic sensitivity for chronic pancreatitis • Diagnostic specificity is comparable for all imaging modalities • EUS and ERCP are outperformers and US has the lowest accuracy • The choice of imaging can be made based on clinical considerations.

Acute pancreatitis: international classification and nomenclature.

The incidence of acute pancreatitis (AP) is increasing and it is associated with a major healthcare concern. New insights in the pathophysiology, better imaging techniques, and novel treatment options for complicated AP prompted the update of the 1992 Atlanta Classification. Updated nomenclature for pancreatic collections based on imaging criteria is proposed. Adoption of the newly Revised Classification of Acute Pancreatitis 2012 by radiologists should help standardise reports and facilitate accurate conveyance of relevant findings to referring physicians involved in the care of patients with AP. This review will clarify the nomenclature of pancreatic collections in the setting of AP.

The predictive value of proteinuria in acute pancreatitis.

BACKGROUND/OBJECTIVES: Acute pancreatitis has a highly variable clinical course. Early and reliable predictors for the severity of acute pancreatitis are lacking. Proteinuria appears to be a useful predictor of disease severity and outcome in a variety of clinical conditions. This study aims to investigate the predictive value of proteinuria on admission for the severity of acute pancreatitis compared with other commonly used predictors; the APACHE II score, Modified Glasgow score and C-reactive protein (CRP). METHODS: This is a post-hoc analysis of 64 patients admitted with acute pancreatitis treated in one teaching hospital, who participated in a previous randomized trial. Proteinuria was defined as a Protein/Creatinine (P/C) ratio >23 mg/mmol. The primary endpoint was severe acute pancreatitis. Secondary endpoints included infectious complications, need for invasive intervention, ICU stay and in-hospital mortality. RESULTS: Proteinuria was present in 30/64 patients (47%). Eleven patients (17%) had severe acute pancreatitis. There was no difference in incidence of severe acute pancreatitis between patients with and without proteinuria: 6/30 patients (20%) versus 5/34 patients (15%) respectively (p = 0.58). Likewise, the occurrence of infectious complications, need for intervention and ICU stay and mortality did not differ significantly (p = 0.58, p = 0.99, p = 0.33 and p = 0.60 respectively). The diagnostic performance of the P/C ratio for the prediction of severe pancreatitis was inferior to the Modified Glasgow score (p = 0.04) and CRP (p = 0.03). CONCLUSION: Proteinuria on admission does not seem to be a reliable predictor for disease severity in acute pancreatitis. The diagnostic performance of the P/C ratio is inferior to the Modified Glasgow score and CRP.

Staged multidisciplinary step-up management for necrotizing pancreatitis.

BACKGROUND: Some 15 per cent of all patients with acute pancreatitis develop necrotizing pancreatitis, with potentially significant consequences for both patients and healthcare services. METHODS: This review summarizes the latest insights into the surgical and medical management of necrotizing pancreatitis. General management strategies for the treatment of complications are discussed in relation to the stage of the disease. RESULTS: Frequent clinical evaluation of the patient's condition remains paramount in the first 24-72 h of the disease. Liberal goal-directed fluid resuscitation and early enteral nutrition should be provided. Urgent endoscopic retrograde cholangiopancreatography is indicated when cholangitis is suspected, but it is unclear whether this is appropriate in patients with predicted severe biliary pancreatitis without cholangitis. Antibiotic prophylaxis does not prevent infection of necrosis and antibiotics are not indicated as part of initial management. Bacteriologically confirmed infections should receive targeted antibiotics. With the more conservative approach to necrotizing pancreatitis currently advocated, fine-needle aspiration culture of pancreatic or extrapancreatic necrosis will less often lead to a change in management and is therefore indicated less frequently. Optimal treatment of infected necrotizing pancreatitis consists of a staged multidisciplinary 'step-up' approach. The initial step is drainage, either percutaneous or transluminal, followed by surgical or endoscopic transluminal debridement only if needed. Debridement is delayed until the acute necrotic collection has become 'walled-off'. CONCLUSION: Outcome following necrotizing pancreatitis has improved substantially in recent years as a result of a shift from early surgical debridement to a staged, minimally invasive, multidisciplinary, step-up approach.

Timing of cholecystectomy after mild biliary pancreatitis.

BACKGROUND: The aim of the study was to evaluate recurrent biliary events as a consequence of delay in cholecystectomy following mild biliary pancreatitis. METHODS: Between 2004 and 2007, patients with acute pancreatitis were registered prospectively in 15 Dutch hospitals. Patients with mild biliary pancreatitis were candidates for cholecystectomy. Recurrent biliary events requiring admission before and after cholecystectomy, and after endoscopic sphincterotomy (ES), were evaluated. RESULTS: Of 308 patients with mild biliary pancreatitis, 267 were candidates for cholecystectomy. Eighteen patients underwent cholecystectomy during the initial admission, leaving 249 potential candidates for cholecystectomy after discharge. Cholecystectomy was performed after a median of 6 weeks in 188 patients (75·5 per cent). Before cholecystectomy, 34 patients (13·7 per cent) were readmitted for biliary events, including 24 with recurrent biliary pancreatitis. ES was performed in 108 patients during the initial admission. Eight (7·4 per cent) of these patients suffered from biliary events after ES and before cholecystectomy, compared with 26 (18·4 per cent) of 141 patients who did not have ES (risk ratio 0·51, 95 per cent confidence interval 0·27 to 0·94; P = 0·015). Following cholecystectomy, eight (3·9 per cent) of 206 patients developed biliary events after a median of 31 weeks. Only 142 (53·2 per cent) of 267 patients were treated in accordance with the Dutch guideline, which recommends cholecystectomy or ES during the index admission or within 3 weeks thereafter. CONCLUSION: A delay in cholecystectomy after mild biliary pancreatitis carries a substantial risk of recurrent biliary events. ES reduces the risk of recurrent pancreatitis but not of other biliary events.

Systematic review of percutaneous catheter drainage as primary treatment for necrotizing pancreatitis.

BACKGROUND: The role of percutaneous catheter drainage (PCD) in patients with (infected) necrotizing pancreatitis was evaluated. METHODS: A systematic literature search was performed. Inclusion criteria were: consecutive cohort of patients with necrotizing pancreatitis undergoing PCD as primary treatment for peripancreatic collections; indication for PCD either (suspected) infected necrosis or symptomatic sterile pancreatic necrosis; and outcomes reported to include percentage of infected peripancreatic collections, need for additional surgical necrosectomy, complications and deaths. Exclusion criteria were: cohort of fewer than five patients; cohort included patients with chronic pancreatitis; selected subgroup of patients with acute pancreatitis studied, such as those with pseudocysts, pancreatic abscesses and/or exclusively sterile pancreatic necrosis; and cohort in which PCD was combined with another minimally invasive strategy and results for PCD alone not reported separately. RESULTS: Eleven studies, including 384 patients, fulfilled the inclusion criteria. Only one study was a randomized controlled trial; most others were retrospective case series. Four studies reported on the presence of organ failure before PCD; this occurred in 67·2 per cent of 116 patients. Infected necrosis was proven in 271 (70·6 per cent) of 384 patients. No additional surgical necrosectomy was required after PCD in 214 (55·7 per cent) of 384 patients. Complications consisted mostly of internal and external pancreatic fistulas. The overall mortality rate was 17·4 per cent (67 of 384 patients). Nine of 11 studies reported mortality separately for patients with infected necrosis undergoing PCD; the mortality rate in this group was 15·4 per cent (27 of 175). CONCLUSION: A considerable number of patients can be treated with PCD without the need for surgical necrosectomy.

Prediction of common bile duct stones in the earliest stages of acute biliary pancreatitis.

BACKGROUND AND STUDY AIMS: Accurate prediction of common bile duct (CBD) stones in acute biliary pancreatitis is warranted to select patients for early therapeutic endoscopic retrograde cholangiopancreatography (ERCP). We evaluated commonly used biochemical and radiological predictors of CBD stones in a large prospective cohort of patients with acute biliary pancreatitis who were undergoing early ERCP. PATIENTS AND METHODS: 167 patients with acute biliary pancreatitis who were undergoing early ERCP (< 72 hours after symptom onset) in 15 Dutch hospitals in 2004 - 2007 were prospectively included. Abdominal ultrasonography and/or computed tomography (CT) was performed on admission and complete liver biochemistry determined daily. We used univariate logistic regression to assess associations between CBD stones found during ERCP (gold standard) and the following parameters: (1) clinical: age, sex, predicted severity; (2) radiological: dilated CBD, impacted stone in CBD; and (3) biochemical: bilirubin, γ-glutamyltransferase (GGT), alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). RESULTS: Out of 167 patients, 94 (56 %) had predicted severe acute biliary pancreatitis, 51 (31%) exhibited a dilated CBD and 15 (9%) had CBD stones on ultrasonography and/or CT. ERCP was performed at a median of 0 days (interquartile range 0 - 1) after admission. CBD stones were found during ERCP in 89/167 patients (53%). In univariate analysis, the only parameters significantly associated with CBD stones were GGT (per 10 units increase: odds ratio 1.02, 95% CI 1.01 - 1.03, P = 0.001) and alkaline phosphatase (per 10 units increase: odds ratio 1.03, 95% CI 1.00 - 1.05, P = 0.028). These and all other tested parameters, however, showed poor positive predictive value (ranging from 0.53 to 0.69) and poor negative predictive value (ranging from 0.46 to 0.67). CONCLUSIONS: The results of this study suggest that commonly used biochemical and radiological predictors of the presence of CBD stones during ERCP in the earliest stages of acute biliary pancreatitis are unreliable.

Large gluteal abscesses as a complication of transgluteal drainage of pelvic abscesses: analysis of three cases and a search of the literature.

BACKGROUND: The percutaneous transgluteal approach is a well-accepted method for drainage of deep pelvic abscesses. Recently, in 3 patients, transgluteal drainage was complicated by the development of large gluteal abscesses requiring multiple surgical interventions. METHODS: This report describes these cases as well as a search of the literature. RESULTS: Three patients with a complicated clinical course after colon resection are described. After CT-guided percutaneous transgluteal drainage of the pelvic abscess, large gluteal abscesses were diagnosed after 2-6 weeks. Subsequent surgical interventions were needed to adequately drain these abscesses. In the literature, transgluteal drainage of pelvic abscesses is well described as a safe and efficient method. However, until now the development of gluteal abscesses has not been mentioned as a complication in the literature. CONCLUSION: In our own experience, a transrectally (radiologically or surgically performed) drainage route is recommended in patients who develop a deep pelvic abscess after bowel resection and suspicion of an anastomotic leak.

[Probiotic prophylaxis in patients with predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial]. / Probioticaprofylaxe bij voorspeld ernstige acute pancreatitis: een gerandomiseerde, dubbelblinde, placebogecontroleerde trial.

OBJECTIVE: To evaluate whether enteral prophylaxis with probiotics in patients with predicted severe acute pancreatitis prevents infectious complications. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. METHOD: A total of 296 patients with predicted severe acute pancreatitis (APACHE II score > or = 8, Imrie score > or = 3 or C-reactive protein concentration > 150 mg/l) were included and randomised to one of two groups. Within 72 hours after symptom onset, patients received a multispecies preparation of probiotics or placebo given twice daily via a jejunal catheter for 28 days. The primary endpoint was the occurrence of one of the following infections during admission and go-day follow-up: infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis or infected ascites. Secondary endpoints were mortality and adverse reactions. The study registration number is ISRCTN38327949. RESULTS: Treatment groups were similar at baseline with regard to patient characteristics and disease severity. Infections occurred in 30% of patients in the probiotics group (46 of 152 patients) and 28% of those in the placebo group (41 of 144 patients; relative risk (RR): 1.1; 95% CI: 0.8-1.5). The mortality rate was 16% in the probiotics group (24 of 152 patients) and 6% (9 of 144 patients) in the placebo group (RR: 2.5; 95% CI: 1.2-5.3). In the probiotics group, 9 patients developed bowel ischaemia (of whom 8 patients died), compared with none in the placebo group (p = 0.004). CONCLUSION: In patients with predicted severe acute pancreatitis, use of this combination of probiotic strains did not reduce the risk of infections. Probiotic prophylaxis was associated with a more than two-fold increase in mortality and should therefore not be administered in this category of patients.

The Atlanta Classification of acute pancreatitis revisited.

BACKGROUND: In a complex disease such as acute pancreatitis, correct terminology and clear definitions are important. The clinically based Atlanta Classification was formulated in 1992, but in recent years it has been increasingly criticized. No formal evaluation of the use of the Atlanta definitions in the literature has ever been performed. METHODS: A Medline literature search sought studies published after 1993. Guidelines, review articles and their cross-references were reviewed to assess whether the Atlanta or alternative definitions were used. RESULTS: A total of 447 articles was assessed, including 12 guidelines and 82 reviews. Alternative definitions of predicted severity of acute pancreatitis, actual severity and organ failure were used in more than half of the studies. There was a large variation in the interpretation of the Atlanta definitions of local complications, especially relating to the content of peripancreatic collections. CONCLUSION: The Atlanta definitions for acute pancreatitis are often used inappropriately, and alternative definitions are frequently applied. Such lack of consensus illustrates the need for a revision of the Atlanta Classification.

Intense adrenal enhancement in patients with acute pancreatitis and early organ failure.

Intense adrenal enhancement has previously been reported in patients with hypovolemic and septic shock. The purpose of this study was to assess whether this computed tomography (CT) finding is also observed in patients presenting with severe acute pancreatitis and early organ failure. A retrospective analysis of a prospectively collected database was performed. Out of 38 consecutive patients with predicted severe acute pancreatitis, 3 patients showed intense bilateral adrenal enhancement on early CT. All patients had early multiple organ failure and subsequently died. In two cases, pathologic correlation was obtained. Intense adrenal enhancement may be a new prognostic indicator in patients with acute pancreatitis, particularly when organ failure is present at the time of CT examination. Further studies are necessary to confirm this observation.

Videoscopic assisted retroperitoneal debridement in infected necrotizing pancreatitis.

Surgical intervention in patients with infected necrotizing pancreatitis generally consists of laparotomy and necrosectomy. This is an invasive procedure that is associated with high morbidity and mortality rates. In this report, we present an alternative minimally invasive technique: videoscopic assisted retroperitoneal debridement (VARD). This technique can be considered a hybrid between endoscopic and open retroperitoneal necrosectomy. A detailed technical description is provided and the advantages over various other minimally invasive retroperitoneal techniques are discussed.

[Timing and choice of intervention in necrotising pancreatitis]. / Timing en keuze van interventie bij necrotiserende pancreatitis.

Three patients, men aged 49, 62 and 33 years, were admitted with acute abdominal symptoms due to necrotising pancreatitis. They underwent multiple interventions during a hospital stay of several months, but ultimately recovered completely. In case of infected (peri-)pancreatic necrosis, intervention is required. Good clinical judgement in the differentiation between the septic inflammatory-response syndrome, sepsis and infected necrosis as the cause of the clinical condition is important. Because of the different intervention strategies, treatment by a team comprising a radiologist, gastroenterologist, intensive care specialist and gastrointestinal surgeon is required. Randomised studies on intervention in infected pancreatic necrosis are lacking. In 2002, to improve the treatment of patients with acute (necrotising) pancreatitis via a combination of research, consultation and centralisation, the Dutch Acute Pancreatitis Study Group was formed.

Endovascular venous stenting in May-Thurner syndrome.

BACKGROUND: Chronic pulsatile compression of the left common iliac vein between the crossing right common iliac artery and the lowest lumbar vertebral body may induce focal intimal proliferation of the vein (May-Thurner syndrome), resulting in impaired venous return and left iliofemoral thrombosis. Corrective surgical treatment requires extensive dissection. In this report, we describe our experience with endovascular venous stenting in May-Thurner syndrome. METHODS: Six patients with symptomatic May-Thurner syndrome were treated with percutaneous transluminal angioplasty and implantation of self-expanding stents. RESULTS Postprocedure phlebography revealed patent iliofemoral veins with unimpeded venous outflow and disappearance of collaterals in all patients. No procedure-related complications occurred. At follow-up (median, 12 months), 5 of 6 patients were free of symptoms. In one patient lower extremity edema was aggravated despite a patent stented segment of the left iliac vein. The patient continues to wear support stockings to compensate for continuing venous insufficiency. Color coded duplex scanning revealed patency at regular intervals in 5 patients. In one patient, occlusion of the stented venous segment with return of symptoms was detected at one month. Patency could not be restored despite catheter-directed thrombolytic therapy. After angioplasty, however, adequate collateral circulation was restored and symptoms resolved completely. CONCLUSIONS: Endovascular venous stenting in May-Thurner syndrome is technically feasible, and leads to reduction of symptoms in the majority of patients with high patency rates in the medium-term. This approach may prove to be a percutaneous alternative to surgical treatment.