Jens Hillingsø

Evaluation of a fast-track programme for patients undergoing liver resection.

Recent developments in perioperative pathophysiology and care have documented evidence‐based, multimodal rehabilitation (fast‐track) to hasten recovery and to decrease morbidity and hospital stay for several major surgical procedures. The aim of this study was to investigate the effect of introducing fast‐track principles for perioperative care in unselected patients undergoing open or laparoscopic liver resection.

Obesity increases mortality in liver transplantation – the Danish experience

Obesity is increasing in the western world at an epidemic rate. The USA results in obese patients undergoing orthotopic liver transplantation (OLT) are divergent, and so far no European experience has been reported. This study was designed to determine if obesity is a risk factor for mortality and morbidity in OLT in a medium‐size European center. In a retrospective study of the records of 365 consecutive patients who had undergone OLT from 1990 to 2003, 20 obese patients [body mass index (BMI) > 30 kg/m2] were identified. Their data were compared with those of the nonobese (BMI < 30 kg/m2) patients operated immediately before. There were no differences in demographic data, diagnosis leading to OLT, United Network of Organ Sharing (UNOS) classification, Child‐Pugh score, or preoperative morbidity. The groups were also comparable concerning donor data, duration of operation, use of blood products, intensive care unit (ICU), or hospital admission. Mortality was, however, significantly increased in the obese group (P = 0.01). Our study clearly demonstrates an increased mortality in obese patients undergoing OLT and the relative scarcity of organs taken into account, it seems reasonable to consider obesity as a relative contraindication to OLT.

Liver Transplantation for Erythropoietic Protoporphyria in Europe

Liver transplantation is an established lifesaving treatment for patients with severe protoporphyric liver disease, but disease recurrence in the graft occurs for the majority of recipients. Severe burn injuries may occur when protective light filters are not used with surgical luminaires. Motor neuropathy with an unclear pathogenesis is a frequent complication. We retrospectively studied 35 transplants performed for protoporphyric liver disease in 31 European patients between 1983 and 2008. Most of the patients were male (61.3%), and the mean age at the time of primary transplantation was 39 years (range = 9‐60 years). The overall patient survival rates were 77% at 1 year and 66% at 5 and 10 years. The overall rate of disease recurrence in the graft was 69%. Forty‐three percent of the patients experienced recurrence within a year, but this was often a transient finding that was associated with other graft complications. Phototoxic injuries due to surgical luminaires were seen in 25.0% of the patients who were not protected by filters, but these injuries were not seen in the 9 patients who were protected by filters. Significant motor neuropathies requiring prolonged ventilation complicated the postoperative course for 5 of the 31 patients (16.1%). Hematopoietic stem cell transplantation was performed for 3 patients to prevent graft loss due to disease recurrence. Prognostic markers are needed to identify patients prone to severe protoporphyric liver disease so that curative stem cell transplantation can be offered to select patients instead of liver transplantation. Liver Transpl 17:1021–1026, 2011.

Usefulness of contrast-enhanced transabdominal ultrasound for tumor classification and tumor staging in the pancreatic head.

Abstract Objective. To evaluate contrast-enhanced ultrasound (CEUS) and compare it to ultrasound (US) and 64-slice-CT (64-CT) for diagnosing, staging and evaluation of resectability of pancreatic cancer. Material and methods. US, CEUS and 64-CT were performed in 49 consecutive patients with pancreatic head tumors and with suspected cancer. After evaluation 44 patients had pancreatic head adenocarcinoma and 5 had chronic pancreatitis, all confirmed by histology. Results. The sensitivity of US, CEUS and 64-CT for diagnosing malignant pancreatic head tumors was 89%, 86% and 93%, respectively, and the overall accuracy was 82%, 86% and 88% respectively. There was no significant difference in the malignant tumor size measurement between US and CEUS (p = 0.3619) or between US and 64-CT (p = 0.2129), but a significant difference was seen in the size measured by CEUS and 64-CT (p = 0.0197). The CEUS measurements on the tumor size were smaller. The overall accuracy for M staging of the patients who had surgery for adenocarcinoma was 86% and 90% for US + CEUS and 64-CT, respectively. By performing the CEUS and 64-CT we additionally found, respectively, 35% and 45% non-resectable patients of a group of patients, who were considered resectable on the primary radiological image material. Conclusions. CEUS may be a useful diagnostic tool in the diagnosis and staging of pancreatic head tumors. For the assessment of resectability CEUS did not prove useful. However, CEUS seemed very useful as an additional instrument in the detection of non-resectable patients already considered resectable on primary radiological image material.

Liver transplantation in polycystic liver disease: A relevant treatment modality for adults?

Objective. Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about whether it is a relevant modality considering the absence of liver failure, relative organ shortage, perioperative risks and lifelong immunosuppression. The purpose of this study was to review our experience of LTX for PLD and to compare the survival with the overall survival of patients who underwent LTX from 1992 to 2005. Material and methods. A retrospective study of the journals of 440 patients, who underwent 506 LTXs between 1992 and 2005, showed that 14 patients underwent LTX for PLD. All patients had normal liver function. Three were receiving haemodialysis and thus underwent combined liver/kidney transplantation. One patient had undergone kidney transplantation 10 years earlier. Results. Median follow-up was 55 months. One patient who underwent combined transplantation died after 5.4 months because of multiorgan failure after re-LTX, and one patient, with well-functioning grafts, died of lymphoma after 7 months. At present 12 patients are alive, relieved of symptoms and with good graft function. Conclusions. We conclude that patients treated for PLD by LTX have a good long-term prognosis and excellent relief of symptoms and that LTX might be considered in severe cases of PLD, where conventional surgery is not an option.

Factors associated with the development of cytomegalovirus infection following solid organ transplantation

Abstract Background: Infection with cytomegalovirus (CMV) remains a potentially serious complication in transplant patients. In this study we explored the risk factors for CMV infection in the 12 months following a solid organ transplantation (n = 242) in patients monitored for CMV infection from 2004 to 2007. Methods: CMV infection was defined as 2 consecutive quantifiable CMV-polymerase chain reaction (PCR) values or 1 measurement of >3000 copies/ml. Data describing pre- and post-transplantation variables were extracted from electronic health records. Time to CMV infection was investigated using Cox proportional hazards analysis. Results: Overall, 31% (75/242) of solid organ transplant patients developed CMV infection: 4/8 (50.0%) heart, 15/43 (34.9%) liver, 30/89 (33.7%) lung and 26/102 (25.5%) kidney transplant patients. The risk of CMV infection according to donor (D)/recipient (R) CMV serostatus (positive + or negative−) was highest for D+/R−(adjusted hazard ratio 2.6, 95% confidence interval 1.6–4.2) vs D+/R+, and was reduced for D−/R+(adjusted hazard ratio 0.2, 95% confidence interval 0.2–0.8) vs D+/R+. Conclusion: Positive donor CMV-serostatus is a major risk factor for CMV-infection in CMV-na ve recipients, but also in recipients with positive CMV-serostatus. Conversely, if donor is CMV serostatus is negative, the risk of CMV infection is low, irrespective of recipients CMV-serostatus. These findings suggest poorer immune function towards donor-induced strains of CMV versus recipient own latent strains.

Ventilatory strategy during liver transplantation: implications for near-infrared spectroscopy-determined frontal lobe oxygenation

Background: As measured by near infrared spectroscopy (NIRS), cerebral oxygenation (ScO2) may be reduced by hyperventilation in the anhepatic phase of liver transplantation surgery (LTx). Conversely, the brain may be subjected to hyperperfusion during reperfusion of the grafted liver. We investigated the relationship between ScO2 and end-tidal CO2 tension (EtCO2) during the various phases of LTx. Methods: In this retrospective study, 49 patients undergoing LTx were studied. Forehead ScO2, EtCO2, minute ventilation (VE), and hemodynamic variables were recorded from the beginning of surgery through to the anhepatic and reperfusion phases during LTx. Results: In the anhepatic phase, ScO2 was reduced by 4.3% (95% confidence interval: 2.5–6.0%; P < 0.0001), EtCO2 by 0.3 kPa (0.2–0.4 kPa; P < 0.0001), and VE by 0.4 L/min (0.1–0.7 L/min; P = 0.0018). Conversely, during reperfusion of the donated liver, ScO2 increased by 5.5% (3.8–7.3%), EtCO2 by 0.7 kPa (0.5–0.8 kPa), and VE by 0.6 L/min (0.3–0.9 L/min; all P < 0.0001). Changes in ScO2 were correlated to those in EtCO2 (Pearson r = 0.74; P < 0.0001). Conclusion: During LTx, changes in ScO2 are closely correlated to those of EtCO2. Thus, this retrospective analysis suggests that attention to maintain a targeted EtCO2 would result in a more stable ScO2 during the operation.

The Effect of Preoperative Oral Immunonutrition on Complications and Length of Hospital Stay After Elective Surgery for Pancreatic Cancer–A Randomized Controlled Trial

ABSTRACT Major gastrointestinal surgery is associated with immune suppression and a high risk of postoperative complications. The aim of this open, randomized controlled trial was to examine the effect of supplementary per oral immunonutrition (IN) seven days before surgery for pancreatic cancer (PC) on postoperative complications and length of hospital stay (LOS). Secondary outcomes were the changes in functional capability and body weight (BW). Consecutive patients referred for surgery for diagnosed or plausible PC were included. The patients in the intervention group received supplementary IN (Oral Impact®, Nestlé) to reach a goal of 1.5 g protein/kg BW. The control group continued their habitual diet. Complications and LOS were independently assessed by the surgical staff. Secondary outcomes were measured 10, 20, and 30 days postoperatively. Thirty-five patients were included, of whom 19 (54%) were allocated to the intervention group. The doses of IN ranged from 250 to 1000 ml per day and the median compliance was 100 (0–100%). Based on the principle of intention-to-treat, no significant differences were found between the groups. We conclude that the lack of effect could be due to the limited dosage of IN, and/or because only 40% of the patients were at nutritional risk.

Histone deactylase gene expression profiles are associated with outcomes in blunt trauma patients

BACKGROUND Treatment with histone deacetylase (HDAC) inhibitors, such as valproic acid, increases survival in animal models of trauma and sepsis. Valproic acid is a pan-inhibitor that blocks most of the known HDAC isoforms. Targeting individual HDAC isoforms may increase survival and reduce complications, but little is known of the natural history of HDAC gene expression following trauma. We hypothesized that distinct HDAC isoform gene expression patterns would be associated with differences in outcomes following trauma. METHODS Twenty-eight–day longitudinal HDAC leukocyte gene expression profiles in 172 blunt trauma patients were extracted from the Inflammation and the Host Response to Injury (Glue Grant) data set. Outcome was classified as complicated (death or no recovery by Day 28, n = 51) or uncomplicated (n = 121). Mixed modeling was used to compare the HDAC expression trajectories between the groups, corrected for Injury Severity Score (ISS), base deficit, and volume of blood products transfused during the initial 12 hours following admission. Weighted gene correlation network analysis identified modules of genes with significant coexpression, and HDAC genes were mapped to these modules. Biologic function of these modules was investigated using the Gene Ontology database. RESULTS Elevated longitudinal HDAC expression trajectories for HDAC1, HDAC3, HDAC6, and HDAC11 were associated with complicated outcomes. In contrast, suppressed expression of Sirtuin 3 (SIRT3) was associated with adverse outcome (p < 0.01). Weighted gene correlation network analysis identified significant coexpression of HDAC and SIRT genes with genes involved in ribosomal function and down-regulation of protein translation in response to stress (HDAC1), T-cell signaling, and T-cell selection (HDAC3) as well as coagulation and hemostasis (SIRT3). No coexpression of HDAC11 was identified. CONCLUSION Expression trajectories of HDAC1, HDAC3, HDAC6, HDAC11, and SIRT3 correlate with outcomes following trauma and may potentially serve as biomarkers. They may also be promising targets for pharmacologic intervention. The effects of HDAC and SIRT gene expression in trauma may be mediated through pathways involved in ribosomal and T-cell function as well as coagulation and hemostasis. LEVEL OF EVIDENCE Prognostic study, level III.

Goblet Cell Carcinoids: Characteristics of a Danish Cohort of 83 Patients

Background Appendiceal goblet cell carcinoids (GCCs) exhibit neuroendocrine and adenocarcinoma features. Patients and Methods Analysis of demography, pathology, prognostic markers, treatment and survival in 83 GCC patients (f/m: 56/27) diagnosed 1992-2013. Results Median age for f/m was 59/58 years, respectively, and similar for localized and disseminated disease. At diagnosis 54 patients had localized appendiceal disease (f/m: 29/25). According to TNM 24% had Stage I, 70% had Stage II and 6% had Stage III. Twenty-nine patients had disseminated disease (f/m: 27/2). Chromogranin A, synaptophysin and p53 were positive in >90%. Serotonin was positive in 70%. Median Ki67 index was 32% (6-75%) and higher in Tang group C (50%) compared to group A (30%; p<0.0001), and group B (30%; p<0.004). All patients had surgery. Sixty-three (76%) had radical resections including all patients with localized disease. Median OS was 83 months. The 1-, 5- and 10-year survival rates were 90%, 58%, and 38%, respectively. For localized disease OS was 164 months and 1-, 5- and 10-year survival rates were 100%, 80%, and 55%, respectively. For disseminated disease OS was 19 months and 1-, 5- and 10-year survival rates were 73%, 18% and 6%, respectively. The 1-, 5- and 10 year-survival rates for f/m were 87%/96%, 49%/76% and 31%/57%, respectively (p = 0.02). According to the Tang classification group A, B, and C OS was 118, 83 and 20 months, respectively (p = 0.0002). Conclusion The Tang classification was found to be a significant prognostic factor, while the Ki67 index was not. Localized GCCs occurred equally in males and females, while disseminated GCCs were mostly seen in females. Median age of patients with localized disease and disseminated disease was identical. Cox regression analysis found Stage IV, focally positive synaptophysin and non-radical surgery as strongest negative prognostic factors.