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1.  Pheochromocytoma crisis 
Clinical Case Reports  2013;2(1):14.
Key Clinical Message
Adrenergic crisis induced by a pheochromocytoma leads to life-threatening catecholamine-induced hemodynamic disturbances. Successful treatment of a pheochromocytoma crisis demands prompt diagnosis, vigorous pharmacological therapy and emergent tumor removal, if the patient continues to deteriorate
PMCID: PMC4184766  PMID: 25356229
Critical care medicine; general surgery
2.  Ischemia/Reperfusion Injury in Liver Surgery and Transplantation 
HPB Surgery  2012;2012:453295.
PMCID: PMC3546476  PMID: 23345924
3.  Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report 
The lancet oncology  2011;13(1):e11-e22.
Although liver transplantation is a widely accepted treatment for hepatocellular carcinoma (HCC), much controversy remains and there is no generally accepted set of guidelines. An international consensus conference was held on Dec 2–4, 2010, in Zurich, Switzerland, with the aim of reviewing current practice regarding liver transplantation in patients with HCC and to develop internationally accepted statements and guidelines. The format of the conference was based on the Danish model. 19 working groups of experts prepared evidence-based reviews according to the Oxford classification, and drafted recommendations answering 19 specific questions. An independent jury of nine members was appointed to review these submissions and make final recommendations, after debates with the experts and audience at the conference. This report presents the final 37 statements and recommendations, covering assessment of candidates for liver transplantation, criteria for listing in cirrhotic and non-cirrhotic patients, role of tumour downstaging, management of patients on the waiting list, role of living donation, and post-transplant management.
PMCID: PMC3417764  PMID: 22047762
4.  Complications in colorectal surgery: risk factors and preventive strategies 
Open or laparoscopic colorectal surgery comprises of many different types of procedures for various diseases. Depending upon the operation and modifiable and non-modifiable risk factors the intra- and postoperative morbidity and mortality rate vary. In general, surgical complications can be divided into intraoperative and postoperative complications and usually occur while the patient is still in the hospital.
A literature search (1980-2009) was carried out, using MEDLINE, PubMed and the Cochrane library.
This review provides an overview how to identify and minimize intra- and postoperative complications. The improvement of different treatment strategies and technical inventions in the recent decade has been enormous. This is mainly attributable to the increase in the laparoscopic approach, which is now well accepted for many procedures. Training of the surgeon, hospital volume and learning curves are becoming increasingly more important to maximize patient safety, surgeon expertise and cost effectiveness. In addition, standardization of perioperative care is essential to minimize postoperative complications.
This review summarizes the main perioperative complications of colorectal surgery and influencable and non-influencable risk factors which are important to the general surgeon and the relevant specialist as well. In order to minimize or even avoid complications it is crucial to know these risk factors and strategies to prevent, treat or reduce intra- and postoperative complications.
PMCID: PMC2852382  PMID: 20338045
5.  Reconstruction of the gastric passage by a side-to-side gastrogastrostomy after failed vertical-banded gastroplasty: a case report 
Vertical-banded gastroplasty, a technique that is commonly performed in the treatment of morbid obesity, represents a nonadjustable restrictive procedure which reduces the volume of the upper stomach by a vertical stapler line. In addition, a textile or silicone band restricts food passage through the stomach.
Case presentation
A 71-year-old woman presented with a severe gastric stenosis 11 years after vertical gastroplasty. We describe a side-to-side gastrogastrostomy as a safe surgical procedure to restore the physiological gastric passage after failed vertical-banded gastroplasty.
Occasionally, restrictive procedures for morbid obesity cannot be converted into an alternative bariatric procedure to maintain weight control. This report demonstrates that a side-to-side gastrogastrostomy is a feasible and safe procedure.
PMCID: PMC2424062  PMID: 18513454
6.  A lymphotoxin-driven pathway to hepatocellular carcinoma 
Cancer cell  2009;16(4):295-308.
Hepatitis B and C viruses (HBV, HCV) cause chronic hepatitis and hepatocellular carcinoma (HCC) by poorly understood mechanisms. We show that cytokines lymphotoxin (LT) α, β and their receptor (LTβR) are upregulated in HBV- or HCV-induced hepatitis and HCC. Liver-specific LTαβ expression in mice induces liver inflammation and HCC causally linking hepatic LT overexpression to hepatitis and HCC. Development of HCC, composed in part of A6+ oval cells, depends on lymphocytes and IKappa B kinase β expressed by hepatocytes but is independent of TNFR1. In vivo LTβR stimulation implicates hepatocytes as the major LT-responsive liver cells and LTβR inhibition in LTαβ-transgenic mice with hepatitis suppresses HCC formation. Thus, sustained LT signaling represents a pathway involved in hepatitis-induced HCC.
PMCID: PMC4422166  PMID: 19800575
Journal of hepatology  2014;60(5):1032-1039.
Background & Aims:
Organ shortage has led to the use of steatotic livers in transplantation, despite their elevated susceptibility to ischemia/reperfusion injury (IRI). Matrix metalloproteinase-9 (MMP-9), an inducible gelatinase, is emerging as a central mediator of leukocyte traffic into inflamed tissues. However, its role in steatotic hepatic IRI has yet to be demonstrated.
We examined the function of MMP-9 in mice fed with a high-fat diet (HFD), which developed approximately 50% hepatic steatosis, predominantly macrovesicular, prior to partial hepatic IRI.
The inability of MMP-9−/− deficient steatotic mice to express MMP-9 significantly protected these mice from liver IRI. Compared to fatty controls, MMP-9−/− steatotic livers showed significantly reduced leukocyte infiltration, proinflammatory cytokine expression, and liver necrosis. Loss of MMP-9 activity preserved platelet endothelial cell adhesion molecule-1 (PECAM-1) expression, a modulator of vascular integrity at the endothelial cell–cell junctions in steatotic livers after IRI. Using in vitro approaches, we show that targeted inhibition of MMP-9 sheltered the extracellular portion of PECAM-1 from proteolytic processing, and disrupted leukocyte migration across this junctional molecule. Moreover, the evaluation of distinct parameters of regeneration, proliferating cell nuclear antigen (PCNA) and histone H3 phosphorylation (pH3), provided evidence that hepatocyte progression into S phase and mitosis was notably enhanced in MMP-9−/− steatotic livers after IRI.
MMP-9 activity disrupts vascular integrity at least partially through a PECAM-1 dependent mechanism and interferes with regeneration of steatotic livers after IRI. Our novel findings establish MMP-9 as an important mediator of steatotic liver IRI.
PMCID: PMC3995823  PMID: 24412604
MMP-9; PECAM-1; hepatic steatosis; liver ischemia reperfusion injury
8.  Patient Safety in Surgery Reviewer acknowledgement 2014 
Contributing reviewers
The Editors of Patient Safety in Surgery would like to thank all our reviewers who have contributed to the journal in Volume 8 (2014).
PMCID: PMC4369068  PMID: 25798195
9.  Reviewer Acknowledgement 2013 
Contributing reviewers
The Editors of Patient Safety in Surgery would like to thank all our reviewers who have contributed to the journal in Volume 7 (2013).
PMCID: PMC4120970  PMID: 25093040
10.  Successful Salvage Chemotherapy with FOLFIRINOX for Recurrent Mixed Acinar Cell Carcinoma and Ductal Adenocarcinoma of the Pancreas in an Adolescent Patient 
Case Reports in Oncology  2013;6(3):497-503.
Pancreatic tumors are rare in children and adolescents. Here, we report the case of a 15-year-old boy who presented with a mixed acinar cell carcinoma/ductal adenocarcinoma with blastomatous components. He received multimodal treatment including various chemotherapy regimens and multistep surgery including liver transplantation. Introduction of FOLFIRINOX after relapse repeatedly achieved a durable metabolic and clinical response with good quality of life.
PMCID: PMC3806674  PMID: 24163668
FOLFIRINOX; Acinar cell carcinoma; Ductal adenocarcinoma; Pancreatoblastoma; Pancreatic cancer; Autologous stem cell transplantation; Multimodal treatment
12.  From abstract to impact in cardiovascular research: factors predicting publication and citation 
European Heart Journal  2012;33(24):3034-3045.
Through a 4-year follow-up of the abstracts submitted to the European Society of Cardiology Congress in 2006, we aimed at identifying factors predicting high-quality research, appraising the quality of the peer review and editorial processes, and thereby revealing potential ways to improve future research, peer review, and editorial work.
Methods and results
All abstracts submitted in 2006 were assessed for acceptance, presentation format, and average reviewer rating. Accepted and rejected studies were followed for 4 years. Multivariate regression analyses of a representative selection of 10% of all abstracts (n= 1002) were performed to identify factors predicting acceptance, subsequent publication, and citation. A total of 10 020 abstracts were submitted, 3104 (31%) were accepted for poster, and 701 (7%) for oral presentation. At Congress level, basic research, a patient number ≥ 100, and prospective study design were identified as independent predictors of acceptance. These factors differed from those predicting full-text publication, which included academic affiliation. The single parameter predicting frequent citation was study design with randomized controlled trials reaching the highest citation rates. The publication rate of accepted studies was 38%, whereas only 24% of rejected studies were published. Among published studies, those accepted at the Congress received higher citation rates than rejected ones.
Research of high quality was determined by study design and largely identified at Congress level through blinded peer review. The scientometric follow-up revealed a marked disparity between predictors of full-text publication and those predicting citation or acceptance at the Congress.
PMCID: PMC3530902  PMID: 22669850
Scientific quality; Peer review; Publication; Impact
13.  IFN-γ-receptor signaling ameliorates transplant vasculopathy through attenuation of CD8+ T-cell-mediated injury of vascular endothelial cells 
European journal of immunology  2010;40(3):733-743.
Occlusive transplant vasculopathy (TV) is the major cause for chronic graft rejection. Since endothelial cells (EC) are the first graft cells encountered by activated host lymphocytes, it is important to delineate the molecular mechanisms that coordinate the interaction of EC with activated T cells. Here, the interaction of CD8+ T cells with Ag-presenting EC in vivo was examined using a transgenic heart transplantation model with β-galactosidase (β-gal) expression exclusively in EC (Tie2-LacZ hearts). We found that priming with β-gal peptide-loaded DC failed to generate a strong systemic IFN-γ response, but elicited pronounced TV in both IFN-γ receptor (IFNGR)-competent, and ifngr−/− Tie2-LacZ hearts. In contrast, stimulation of EC-specific CD8+ T cells with β-gal-recombinant mouse cytomegalovirus (MCMV-LacZ) in recipients of ifngr+/+ Tie2-LacZ hearts did not precipitate significant TV. However, MCMV-LacZ infection of recipients of ifngr−/− Tie2-LacZ hearts led to massive activation of β-gal-specific CD8 T cells, and led to development of fulminant TV. Further analyses revealed that the strong systemic IFN-γ “storm” associated with MCMV infection induced upregulation of programmed death-1 ligand 1 (PD-L1) on EC, and subsequent attenuation of programmed death-1 (PD-1)-expressing EC-specific CD8+ T cells. Thus, IFNGR signaling in ECs activates a potent peripheral negative feedback circuit that protects vascularized grafts from occlusive TV.
PMCID: PMC3247644  PMID: 20049875
Chronic rejection; CTL; IFN-γ-receptor; PD-L1; Transplantation; Vascular endothelial cells
14.  Laparoscopic gastric pouch and remnant resection: a novel approach to refractory anastomotic ulcers after Roux-en-Y Gastric Bypass: Case report 
BMC Surgery  2011;11:33.
Anastomotic or marginal ulcers occur in 0.6 to 16% of patients after laparoscopic Roux-en-Y-Gastric Bypass. Initial therapy aims at eliminating known risk factors including smoking, Helicobacter pylori infection, use of non-steroidal anti-inflammatory drugs and inhibition of gastric acid secretion. While this approach is successful in 68 to 88% of the cases, up to one third of patients need a subsequent surgical revision. However, marginal ulcers still recur in up to 10% of cases after revisional surgery, thus constituting a serious challenge for bariatric surgeons.
Case presentation
We herein report a case of an insidious marginal ulcer refractory to both medical therapy with high-dosed proton pump inhibitors and sucralfate as well as surgical therapy consisting of the lengthening of a short alimentary limb and later resection of the gastroenterostomy and construction of a new tension-free anastomosis. Only after gastrectomy by laparoscopic en-bloc resection of the gastrojejunostomy, the gastric pouch and resection of the gastric remnant with reconstruction by esophagojejunostomy the patient remained free of symptoms.
By laparoscopic resection of the entire gastric pouch and the gastric remnant the risk to leave a suboptimally vascularised or even ischemic pouch in situ was avoided. The esophagojejunostomy was then created in healthy, good vascularised tissue. In our case this novel approach was effective in the management of a refractory anastomotic ulcer and might represent a rescue option when simple revision of the gastrojejunostomy fails.
PMCID: PMC3247190  PMID: 22136170
Roux-en-Y-Gastric Bypass; bariatric surgery; anastomotic ulcer; marginal ulcer; obesity
15.  Perception of surgical complications among patients, nurses and physicians: a prospective cross-sectional survey 
Several scores grade the severity of post-operative complications but it is unclear whether such scores truly reflect the perception of patients and practicing nurses and physicians.
Study Design
227 patients, 143 nurses and 245 physicians independently rated the severity of 30 common post-operative complications on a numerical analogue scale from 0 (not severe at all) to 100 (extremely severe) while being blinded towards the Clavien-Dindo classification. We considered a difference in ratings of >10 to be clinically important in distinguishing between grades of severity and groups. We evaluated the level of reproducibility of responses by calculating intraclass correlation coefficients (ICC) and compared scores across severity grades and between groups using the generalized estimating equations.
Reproducibility of the ratings was good for all three groups (ICCpatients 0.71 (95%-CI 0.64-0.76), ICCnurses 0.83 (0.78-0.87) and ICCphysicians 0.87 (0.83-0.90)). The participants' perceptions of the severity of complications reflected the Clavien-Dindo classification (median of grade I: 20 (IQR 10-30), grade II: 40 (31.3-52.5), grade IIIa: 50 (40-60), grade IIIb: 70 (60-75), grade IVa: 85 (80-90) and grade IVB: 95 (90-100)). Although patients' perception differed significantly from those of physicians (average difference -8.7 (95%-CI -10.4 to -6.9, p < 0.001) and nurses (difference -2.8 (-4.8 to -0.8, p = 0.007) they did not reach our thresholds for clinical importance.
The severity of post-operative complications is perceived similarly by patients, nurses and physicians and reflects the Clavien-Dindo classification well. Our results support the use of Clavien-Dindo classification system as part of the shared or informed decision making process.
PMCID: PMC3284430  PMID: 22107603
Perception; surgical complications; patients; nurses and physicians
16.  Cosmesis and body image after single-port laparoscopic or conventional laparoscopic cholecystectomy: a multicenter double blinded randomised controlled trial (SPOCC-trial) 
BMC Surgery  2011;11:24.
Emerging attempts have been made to reduce operative trauma and improve cosmetic results of laparoscopic cholecystectomy. There is a trend towards minimizing the number of incisions such as natural transluminal endoscopic surgery (NOTES) and single-port laparoscopic cholecystectomy (SPLC). Many retrospective case series propose excellent cosmesis and reduced pain in SPLC. As the latter has been confirmed in a randomized controlled trial, patient's satisfaction on cosmesis is still controversially debated.
The SPOCC trial is a prospective, multi-center, double blinded, randomized controlled study comparing SPLC with 4-port conventional laparoscopic cholecystectomy (4PLC) in elective surgery. The hypothesis and primary objective is that patients undergoing SPLC will have a better outcome in cosmesis and body image 12 weeks after surgery. This primary endpoint is assessed using a validated 8-item multiple choice type questionnaire on cosmesis and body image. The secondary endpoint has three entities: the quality of life 12 weeks after surgery assessed by the validated Short-Form-36 Health Survey questionnaire, postoperative pain assessed by a visual analogue scale and the use of analgesics. Operative time, surgeon's experience with SPLC and 4PLC, use of additional ports, conversion to 4PLC or open cholecystectomy, length of stay, costs, time of work as well as intra- and postoperative complications are further aspects of the secondary endpoint. Patients are randomly assigned either to SPLC or to 4PLC. Patients as well as treating physicians, nurses and assessors are blinded until the 7th postoperative day. Sample size calculation performed by estimating a difference of cosmesis of 20% (alpha = 0.05 and beta = 0.90, drop out rate of 10%) resulted in a number of 55 randomized patients per arm.
The SPOCC-trial is a prospective, multi-center, double-blind, randomized controlled study to assess cosmesis and body image after SPLC.
Trial registration
( NCT 01278472
PMCID: PMC3189390  PMID: 21910897
17.  Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study) 
BMC Cancer  2011;11:346.
Despite major improvements in the perioperative outcome of pancreas surgery, the prognosis of pancreatic cancer after curative resection remains poor. Adjuvant chemotherapy increases disease-free and overall survival, but this treatment cannot be offered to a significant proportion of patients due to the surgical morbidity. In contrast, almost all patients can receive (neo)adjuvant chemotherapy before surgery. This treatment is safe and effective, and has resulted in a median survival of 26.5 months in a recent phase II trial. Moreover, neoadjuvant chemotherapy improves the nutritional status of patients with pancreatic cancer. This multicenter phase III trial (NEOPAC) has been designed to explore the efficacy of neoadjuvant chemotherapy.
This is a prospective randomized phase III trial. Patients with resectable cytologically proven adenocarcinoma of the pancreatic head are eligible for this study. All patients must be at least 18 years old and must provide written informed consent. An infiltration of the superior mesenteric vein > 180° or major visceral arteries are considered exclusion criteria. Eligible patients will be randomized to surgery followed by adjuvant gemcitabine (1000 mg/m2) for 6 months or neoadjuvant chemotherapy (gemcitabine 1000 mg/m2, oxaliplatin 100 mg/m2) followed by surgery and the same adjuvant treatment. Neoadjuvant chemotherapy is given four times every two weeks. The staging as well as the restaging protocol after neoadjuvant chemotherapy include computed tomography of chest and abdomen and diagnostic laparoscopy. The primary study endpoint is progression-free survival. According to the sample size calculation, 155 patients need to be randomized to each treatment arm. Disease recurrence will be documented by scheduled computed tomography scans 9, 12, 15, 21 and thereafter every 6 months until disease progression. For quality control, circumferential resection margins are marked intraoperatively, and representative histological sections will be centrally reviewed by a dedicated pathologist.
The NEOPAC study will determine the efficacy of neoadjuvant chemotherapy in pancreatic cancer for the first time and offers a unique potential for translational research. Furthermore, this trial will provide the unbiased overall survival of all patients undergoing surgery for resectable cancer of the pancreatic head.
Trial registration NCT01314027
PMCID: PMC3176241  PMID: 21831266
18.  Quality assessment in surgery: mission impossible? 
PMCID: PMC3787855  PMID: 21092140
19.  Model of end stage liver disease (MELD) score greater than 23 predicts length of stay in the ICU but not mortality in liver transplant recipients 
Critical Care  2010;14(3):R117.
The impact of model of end stage liver disease (MELD) score on postoperative morbidity and mortality is still elusive, especially for high MELD. There are reports of poorer patient outcome in transplant candidates with high MELD score, others though report no influence of MELD score on outcome and survival.
We retrospectively analyzed data of 144 consecutive liver transplant recipients over a 72-month period in our transplant unit, from January 2003 until December 2008 and performed uni- and multivariate analysis for morbidity and mortality, in particular to define the influence of MELD to these parameters.
This study identified MELD score greater than 23 as an independent risk factor of morbidity represented by intensive care unit (ICU) stay longer than 10 days (odds ratio 7.0) but in contrast had no negative impact on mortality. Furthermore, we identified transfusion of more than 7 units of red blood cells as independent risk factor for mortality (hazard ratio 7.6) and for prolonged ICU stay (odds ratio [OR] 7.8) together with transfusion of more than 10 units of fresh frozen plasma (OR 11.6). Postoperative renal failure is a strong predictor of morbidity (OR 7.9) and postoperative renal replacement therapy was highly associated with increased mortality (hazard ratio 6.8), as was hepato renal syndrome prior to transplantation (hazard ratio 13.2).
This study identified MELD score greater than 23 as an independent risk factor of morbidity represented by ICU stay longer than 10 days but in contrast had no negative impact on mortality. This finding supports the transplantation of patients with high MELD score but only with knowledge of increased morbidity.
PMCID: PMC2911764  PMID: 20550662
20.  Challenges in evaluating surgical innovation 
Lancet  2009;374(9695):1097-1104.
Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures—for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.
PMCID: PMC2855679  PMID: 19782875
23.  Human Alveolar Echinococcosis after Fox Population Increase, Switzerland 
Emerging Infectious Diseases  2007;13(6):878-882.
An increase in fox population has led to an increase in incidence of human alveolar echinococcosis.
We analyzed databases spanning 50 years, which included retrospective alveolar echinococcosis (AE) case-finding studies and databases of the 3 major centers for treatment of AE in Switzerland. A total of 494 cases were recorded. Annual incidence of AE per 100,000 population increased from 0.12– 0.15 during 1956–1992 and a mean of 0.10 during 1993–2000 to a mean of 0.26 during 2001–2005. Because the clinical stage of the disease did not change between observation periods, this increase cannot be explained by improved diagnosis. Swiss hunting statistics suggested that the fox population increased 4-fold from 1980 through 1995 and has persisted at these higher levels. Because the period between infection and development of clinical disease is long, the increase in the fox population and high Echinococcus multilocularis prevalence rates in foxes in rural and urban areas may have resulted in an emerging epidemic of AE 10–15 years later.
PMCID: PMC2792858  PMID: 17553227
Alveolar echinococcosis; Echinococcus multilocularis; epidemiology; fox (Vulpes vulpes); zoonosis; incidence; Switzerland; research
24.  Immunoprivileged status of the liver is controlled by Toll-like receptor 3 signaling 
Journal of Clinical Investigation  2006;116(9):2456-2463.
The liver is known to be a classical immunoprivileged site with a relatively high resistance against immune responses. Here we demonstrate that highly activated liver-specific effector CD8+ T cells alone were not sufficient to trigger immune destruction of the liver in mice. Only additional innate immune signals orchestrated by TLR3 provoked liver damage. While TLR3 activation did not directly alter liver-specific CD8+ T cell function, it induced IFN-α and TNF-α release. These cytokines generated expression of the chemokine CXCL9 in the liver, thereby enhancing CD8+ T cell infiltration and liver disease in mice. Thus, nonspecific activation of innate immunity can drastically enhance susceptibility to immune destruction of a solid organ.
PMCID: PMC1555644  PMID: 16955143
25.  Pathogenesis of Cholesterol Gallstones 
HPB Surgery  1991;3(2):79-102.
Cholesterol gallstone disease is extremely common. Three major stages are recognized for stone formation, namely bile that becomes supersaturated with cholesterol, cholesterol nucleation leading to crystal formation and finally retention of the crystals in the gallbladder resulting in stone formation. Supersaturation is common but nucleation into crystals probably requires protein nucleating factors. Impaired motility of the gallbladder causes crystal retention and is probably very important in stone formation.
PMCID: PMC2423600  PMID: 2043512

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