Peter Studer

Hypoxia increases cytoplasmic expression of NDRG1, but is insufficient for its membrane localization in human hepatocellular carcinoma

NDRG1 is a hypoxia‐inducible protein, whose modulated expression is associated with the progression of human cancers. Here, we reveal that NDRG1 is markedly upregulated in the cytoplasm and on the membrane in human hepatocellular carcinoma (HCC). We demonstrate further that hypoxic stress increases the cytoplasmic expression of NDRG1 in vitro, but does not result in its localization on the plasma membrane. However, grown within an HCC‐xenograft in vivo, cells express NDRG1 in the cytoplasm and on the plasma membrane. In conclusion, hypoxia is a potent inducer of NDRG1 in HCCs, albeit requiring additional stimuli within the tumour microenvironment for its recruitment to the membrane.

Indocyanine Green Plasma Disappearance Rate During the Anhepatic Phase of Orthotopic Liver Transplantation

Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI] = 0.8–2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into account.

Surgery-related risk factors.

Purpose of reviewThe surgical procedure remains the key element in the multidisciplinary treatment of a wide variety of degenerative, traumatic, tumorous, congenital, and vascular diseases, resulting in an estimated 234 million surgical interventions worldwide each year. Undesired effects are inherent in any medical intervention, but are of particular interest in an invasive procedure for both the patient and the responsible physician. Major topics in current complication research include perception of key factors responsible for complication development, prediction, and whenever possible, prevention of complications. Recent findingsFor many years, the technical aspects of surgery and the skills of the surgeon her/himself were evaluated and considered as the main sources of surgical complications. However, recent studies identified many nontechnical perspectives, which could improve the overall quality of surgical interventions. SummaryThis article reviews selected, recently published data in this field and aims to point out the complexity and multidimensional facets of surgery-related risk factors.

Evaluation of physical and mental recovery status after elective liver resection.

Background and objective This prospective, clinical pilot trial compared the Short Form 36 Health Survey (SF-36) and a nine-item quality of recovery [Quality of Recovery 9 (QoR-9)] survey to assess the 1-week outcome after liver resection and prediction of postoperative complications from baseline values before liver resection. Methods In 19 patients, the SF-36 was recorded preoperatively (baseline) and on postoperative day (POD) 7. SF-36 z-values (means ± SD) for the physical component summary (PCS) and mental component summary (MCS) were calculated. QoR-9 (score 0–18) was performed at baseline, POD1, POD3, POD5 and POD7. Descriptive analysis and effect sizes (d) were calculated. Results From baseline to POD7, PCS decreased from −0.38 ± 1.30 to −2.10 ± 0.76 (P = 0.002, d = −1.57) and MCS from −0.71 ± 1.50 to −1.33 ± 1.11 (P = 0.061, d = −0.46). QoR-9 was significantly lower at POD1, POD3 and POD5 compared with baseline (P < 0.050, d < −2.0), but not at POD7 (P = 0.060, d = −1.08). Baseline PCS was significantly lower with a high effect size in patients with complications (n = 12) compared with patients without complications (n = 7) (−0.76 ± 1.46 vs. 0.27 ± 0.56; P = 0.044, d = −0.84) but not baseline MCS (P = 0.831, d = −0.10) or baseline QoR-9 (P = 0.384, d = −0.44). Conclusions The SF-36 indicates that liver resection surgery has a higher impact on physical health than on mental health. QoR-9 determines the feasible time course of recovery with a 1-week return to baseline. Preoperative impaired physical health might predict postoperative complications.

Transdiaphragmatic Resuscitative Open Cardiac Massage: Description of the Technique and a First Case-Series of an Alternative Approach to the Heart

BackgroundThe purpose of this paper is to describe the transdiaphragmatic approach to the heart for open CPR in patients that arrest at laparotomy and to present a first case series of patients that have undergone this procedure.MethodsAll patients who had undergone intraperitoneal transdiaphragmatic open CPR between January 1, 2002 and December 31, 2012 were retrieved from the operation registry at Bern University Hospital, Switzerland. Transdiaphragmatic access to the heart is initiated with a 10-cm-long anterocaudal incision in the central tendon of the diaphragm—approximately at 2 o’clock. Internal cardiac compression through the diaphragmatic incision can be performed from both sides of the patient. From the right side of the patient, cardiac massage is performed with the right hand and vice versa.ResultsA total of six patients were identified that suffered cardiac arrest during laparotomy with open CPR performed through the transdiaphragmatic approach. Four patients suffered cardiac arrest during orthotopic liver transplantation and two trauma patients suffered cardiac arrest during damage control laparotomy. In three patients, cardiac activity was never reestablished. However, three patients regained a perfusion heart rhythm and two of these survived to the ICU. One patient ultimately survived to discharge.ConclusionsIn patients suffering cardiac arrest during laparotomy, the transdiaphragmatic approach allows for a rapid, technically easy, and almost atraumatic access to the heart, with excellent CPR performance. After this potentially life-saving procedure, pulmonary or surgical site complications are expected to occur much less compared with the conventionally performed emergency department left-sided thoracotomy.

Granulocyte colony-stimulating factor increases hepatic sinusoidal perfusion during liver regeneration in mice

Conditioning with granulocyte colony-stimulating factor (G-CSF) promotes liver regeneration in an experimental small-for-size liver remnant mouse model. The mechanisms involved in this extraordinary G-CSF effect are unknown. The aim of this study was to investigate the influence of G-CSF on the hepatic microvasculature in the regenerating liver. The hepatic sinusoidal microvasculature and microarchitecture of the regenerating liver were evaluated by intravital microscopy in mice. Three experimental groups were compared: (1) unoperated unconditioned animals (control; n = 5), (2) animals conditioned with G-CSF 48 h after 60% partial hepatectomy (G-CSF-PH; n = 6), and (3) animals sham conditioned 48 h after 60% PH (sham-PH; n = 6). PH led to hepatocyte hypertrophy and increased hepatic sinusoidal velocity in the sham-PH and G-CSF-PH groups. Increased sinusoidal diameter and increased hepatic blood flow were observed in the G-CSF-PH group compared to the sham-PH and control groups. Furthermore, there was a strong positive correlation between spleen weight and hepatic sinusoidal diameter in the G-CSF-PH group. The increased hepatic blood flow could explain the observed benefit of G-CSF conditioning during liver regeneration. These results elucidate an unexplored aspect of pharmacological modulation of liver regeneration and motivate further experiments.

Peri-operative adrenocortical response to low-dose (1 μg) ACTH and relation to postoperative complications in patients undergoing elective abdominal surgery

BACKGROUND To test the hypothesis that reduced responsiveness to adrenocorticotropin (ACTH) stimulation before elective major abdominal surgery is associated with an increased incidence of postoperative complications. METHODS A low-dose (1 microg) ACTH test was performed the day before surgery, during the operation, on the first postoperative day, and before discharge from the hospital in 77 patients undergoing major abdominal surgery (age 62 [47;69] yrs [median, quartiles]; 30 female). Thirty-one patients undergoing minor, non-abdominal surgery (mostly inguinal hernia repair) (age 57 [40;66] yrs; 14 female) served as controls with minor surgical stress. A stimulated plasma cortisol concentration >or=500 nmol/l or an increment of >or=200 nmol/l in response to 1 microg ACTH was defined as normal. Scores for surgical stress and comprehensive risk, postoperative complications, and length of hospital stay (LOS) were assessed. RESULTS On the day before major abdominal surgery, basal and stimulated plasma cortisol were 242 (165;299) nmol/l and 497 (404;568) nmol/l, respectively. Eighteen (23%) patients had an abnormal ACTH test, and 7 of these (39%) had complications versus 25 (42%) of the 59 patients with normal ACTH tests (P = .992). Surgical stress, comprehensive risk, and intra- and postoperative basal cortisol levels were higher and the response to ACTH stimulation smaller in patients with major abdominal compared to minor surgery. The peri-operative course of ACTH responses was not associated with complications or LOS in abdominal surgery patients. CONCLUSION In patients scheduled for abdominal surgery, pre-operatively reduced adrenal response to stimulation with 1 microg ACTH is common but not associated with postoperative complications.

MR-FLIP: A new method that combines FLIP with anatomical information for the spatial compliance assessment of the anal sphincter muscles.

Continence results from a complex interplay between anal canal (AC) muscles and sensorimotor feedback mechanisms. The passive ability of the AC to withstand opening pressure – its compliance – has recently been shown to correlate with continence. A functional lumen imaging probe (FLIP) is used to assess AC compliance, although it provides no anatomical information. Therefore, assessment of the compliance specific anatomical structures has not been possible, and the anatomical position of critical functional zones remains unknown. In addition, the FLIP technique assumes a circular orifice cross‐section, which has not been shown for the AC. To address these shortcomings, a technique combining FLIP with a medical imaging modality is needed.

MR-FLIP: a new method that combines a functional lumen imaging probe with anatomical information for spatial compliance assessment of the anal sphincter muscles

Continence results from a complex interplay between anal canal (AC) muscles and sensorimotor feedback mechanisms. The passive ability of the AC to withstand opening pressure – its compliance – has recently been shown to correlate with continence. A functional lumen imaging probe (FLIP) is used to assess AC compliance, although it provides no anatomical information. Therefore, assessment of the compliance specific anatomical structures has not been possible, and the anatomical position of critical functional zones remains unknown. In addition, the FLIP technique assumes a circular orifice cross‐section, which has not been shown for the AC. To address these shortcomings, a technique combining FLIP with a medical imaging modality is needed.

Adhesions and abdominal pain

Adhesions occur with a high incidence after intra-abdominal surgery but can also develop due to infections, radiation or for idiopathic reasons. The formation of adhesions is initiated by tissue damage and is the result of peritoneal tissue repair involving the activation of the inflammatory system and the coagulation cascade. Acute small bowel obstruction is one of the most common complications and should be diagnosed rapidly using clinical examination and radiological imaging. A complete obstruction is life threatening and in a high percentage of patients requires rapid surgical intervention by laparotomy or laparoscopy depending on the clinical situation and the patients history. Despite numerous investigations, there is no reliable, commonly used method to prevent intra-abdominal adhesions. Minimizing tissue damage and foreign body exposure, avoiding spillage of intestinal and biliary contents as well as a laparoscopic approach seem to have a beneficial effect on the formation of intra-abdominal adhesions.