Imaging the pancreas with photon-counting CT - A review of normal pancreatic anatomy.

PURPOSE: Compared to conventional energy integrating detector CT, Photon-Counting CT (PCCT) has the advantage of increased spatial resolution. The pancreas is a highly complex organ anatomically. The increased spatial resolution of PCCT challenges radiologists' knowledge of pancreatic anatomy. The purpose of this review was to review detailed macroscopic and microscopic anatomy of the pancreas in the context of current and future PCCT. METHOD: This review is based on a literature review of all parts of pancreatic anatomy and a retrospective imaging review of PCCT scans from 20 consecutively included patients without pancreatic pathology (mean age 61.8 years, 11 female), scanned in the workup of pancreatic cancer with a contrast enhanced multiphase protocol. Two radiologists assessed the visibility of the main and accessory pancreatic ducts, side ducts, ampulla, major papilla, minor papilla, pancreatic arteries and veins, regional lymph nodes, coeliac ganglia, and coeliac plexus. RESULTS: The macroscopic anatomy of the pancreas was consistently visualized with PCCT. Visualization of detailed anatomy of the ductal system (including side ducts), papillae, arteries, vein, lymph nodes, and innervation was possible in 90% or more of patients with moderate to good interreader agreement. CONCLUSION: PCCT scans of the pancreas visualizes previously unseen or inconsistently seen small anatomical structures consistently. Increased knowledge of pancreatic anatomy could have importance in imaging of pancreatic cancer and other pancreatic diseases.

Delayed dorsal scapular artery hematoma following blunt thoracic trauma: a case report and review of the literature.

BACKGROUND: The present case contributes to the limited literature on delayed chest wall hematomas following blunt trauma. The literature review provides a summary of similar previously reported cases. CASE PRESENTATION: We report the case of a 59-year-old Caucasian male who presented to the emergency department with a rapidly expanding chest wall hematoma. Six weeks earlier, he had sustained multiple rib fractures and a pneumothorax after falling 4 m from a ladder. Computed tomography angiography was used to identify two sources of active bleeding on the left dorsal scapular artery. The patient underwent surgery with evacuation of the hematoma and ligation of the artery. The patient was hospitalized for 3 days and recovered with no sequelae. CONCLUSIONS: A literature review revealed eight previously reported cases of chest wall hematomas exterior to the endothoracic fascia following blunt trauma. Most cases were initially diagnosed by computed tomography of the chest and finally by angiogram. Management options range from surgical drainage to angiographic embolization. This case is unusual regarding the delay in the development of the hematoma and illustrates the importance of considering this diagnosis even weeks after relevant trauma.

Sarcopenia predicts 90-day mortality in elderly patients undergoing emergency abdominal surgery.

PURPOSE: Image-based measurement of sarcopenia is an established predictor of a decreased outcome for a large variety of surgical procedures. Sarcopenia in elderly patients undergoing emergency abdominal surgery has not been well studied. This study aims to investigate the association between the total psoas area (TPA) and postoperative mortality after 90 days in a group of elderly emergency laparotomy patients. METHODS: We retrospectively reviewed the emergency CT-scans of 150 elderly patients from a consecutive cohort undergoing emergency abdominal surgery at our surgical center. TPA was measured manually at the level of L3 and indexed to patient height. Sarcopenia was defined as having a TPA index below the first quartile for gender in the cohort. Other collected variables were age, vital status/date of death, ASA-score, surgical procedure, and WHO performance score. RESULTS: Overall 90-day mortality was 42.7%. Sarcopenic patients had a higher 90-day mortality (60.5%) than non-sarcopenic patients (36.6%), corresponding to an odds ratio of 2.66 (95% confidence interval 1.2-5.7, p = 0.01). Sarcopenic patients had an increased mortality compared with non-sarcopenic patients (p = 0.0009, Log-rank test), with a clear separation of the two groups within 30 days postoperatively. In a multivariate logistic regression model, with age, ASA-score, and WHO performance score as covariates, sarcopenia was independently associated with 90-day mortality. CONCLUSION: Manual measurement of TPA on an abdominal CT-scan is a relevant risk factor for postoperative mortality in elderly patients undergoing high-risk emergency abdominal surgery. Incorporation of sarcopenia in postoperative risk-prediction models in emergency abdominal surgery should be considered.

Traumatic separation of osseous segments in a double-layered patella.

INTRODUCTION: Double-layered patella is a rare intra-articular disorder associated with multiple epiphyseal dysplasia. PRESENTATION OF CASE: We present a case of a 40-year old man with acute pain in his left knee after a tackle during soccer play. DISCUSSION: Clinical examination and radiographs confirmed the diagnosis of a bilateral double-layered patella with traumatic separation of the osseous segments on the afflicted left side. Surgical management comprised of open arthrotomy and debridement of the bony interface. Stabilization was performed with tension cerclage, supported by a lag screw with excellent outcome at 12 months follow-up. CONCLUSION: It is possible that micromovement in a double-layered patella can dispose to a traumatic coronal segment displacement. Osseous fusion of traumatic patellar segments can be achieved.

[Cerebral fat emboli after elective total hip replacement]. / Cerebrale fedtembolierefter elektiv total hoftealloplastik.

Fat embolism is a well known complication to fractures of long bones, but is less often seen after surgery. The symptoms vary from non- to total pulmonary and circulatory collapse and also include cerebral affection. Cerebral fat embolism is less common, and with varying presentation. This case report describes a case of fatal cerebral fat embolism after total hip replacement in a 75-year-old male. Diagnostics can be difficult but diffusion-weighted MRI can detect infarctions at an early stage. Treatment is symptomatic, and there is often total spontaneous remission of symptoms.

[Intra-abdominal undifferentiated high-grade pleomorphic sarcoma as the cause of mechanical bowel obstruction]. / Intraabdominalt udifferentieret high-grade pleomorft sarkom som årsag til mekanisk tyndtarmsileus.

Primary intra-abdominal undifferentiated high-grade pleomorphic sarcoma is rare with only 40 cases described worldwide. We describe a case of a patient who presented with mechanical bowel obstruction with abdominal undifferentiated high-grade pleomorphic sarcoma. Five-year survival rates have been reported as low as 40-55%, especially due to late diagnosis. Rare diagnoses as in our patient emphasize the need for close collaboration between pathologists, radiologists and surgeons.

A minority of patients discharged within 24 hours after laparoscopic colon resection.

INTRODUCTION: Fast-track laparoscopic colon surgery has gained wide acceptance worldwide. Post-operative hospital stays of 2-5 days have typically been reported. However, in our department some of the patients have been discharged within 24 h after surgery. The aim of this study was to describe differences in demographic and perioperative data between those patients discharged within 24 h and those discharged on days 2-4 post-operatively. MATERIAL AND METHODS: Data were collected retrospectively from August 2008 to May 2012. A total of 24 patients undergoing elective right-sided hemicolectomy or sigmoidectomy for colon cancer were discharged within 24 h. These 24 patients were compared with 209 patients undergoing the same procedures, but discharged on the second to the fourth post-operative day. All patients were operated laparoscopically according to our fast-track regimen. Demographic data and short-term outcomes were compared between the two groups. RESULTS: We found that the median age (64 years versus 70 years) (p = 0.018) as well as the median operating time (120 min. versus 155 min.) (p = 0.002) were significantly lower for the 24-h stay group. No other significant differences were found between the two groups. CONCLUSION: This study showed that discharge within the first 24 h after elective laparoscopic fast-track colon surgery was significantly associated with lower age and shorter duration of surgery. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site.

The binding of zinc (Zn) ions to proteins is important for many cellular events. The theoretical and computational description of this binding (as well as that of other transition metals) is a challenging task. In this paper the binding of the Zn ion to four cysteine residues in the structural site of horse liver alcohol dehydrogenase (HLADH) is studied using a synthetic peptide mimic of this site. The study includes experimental measurements of binding constants, classical free energy calculations from molecular dynamics (MD) simulations and quantum mechanical (QM) electron structure calculations. The classical MD results account for interactions at the molecular level and reproduce the absolute binding energy and the hydration free energy of the Zn ion with an accuracy of about 10%. This is insufficient to obtain correct free energy differences. QM correction terms were calculated from density functional theory (DFT) on small clusters of atoms to include electronic polarisation of the closest waters and covalent contributions to the Zn-S coordination bond. This results in reasonably good agreement with the experimentally measured binding constants and Zn ion hydration free energies in agreement with published experimental values. The study also includes the replacement of one cysteine residue to an alanine. Simulations as well as experiments showed only a small effect of this upon the binding free energy. A detailed analysis indicate that the sulfur is replaced by three water molecules, thereby changing the coordination number of Zn from four (as in the original peptide) to six (as in water).

Identification of an efficacy switch region in the ghrelin receptor responsible for interchange between agonism and inverse agonism.

The carboxyamidated wFwLL peptide was used as a core ligand to probe the structural basis for agonism versus inverse agonism in the constitutively active ghrelin receptor. In the ligand, an efficacy switch could be built at the N terminus, as exemplified by AwFwLL, which functioned as a high potency agonist, whereas KwFwLL was an equally high potency inverse agonist. The wFw-containing peptides, agonists as well as inverse agonists, were affected by receptor mutations covering the whole main ligand-binding pocket with key interaction sites being an aromatic cluster in transmembrane (TM)-VI and -VII and residues on the opposing face of TM-III. Gain-of-function in respect of either increased agonist or inverse agonist potency or swap between high potency versions of these properties was obtained by substitutions at a number of positions covering a broad area of the binding pocket on TM-III, -IV, and -V. However, in particular, space-generating substitutions at position III:04 shifted the efficacy of the ligands from inverse agonism toward agonism, whereas similar substitutions at position III: 08, one helical turn below, shifted the efficacy from agonism toward inverse agonism. It is suggested that the relative position of the ligand in the binding pocket between this "efficacy shift region" on TM-III and the opposing aromatic cluster on TM-VI and TM-VII leads either to agonism, i.e. in a superficial binding mode, or it leads to inverse agonism, i.e. in a more profound binding mode. This relationship between different binding modes and opposite efficacy is in accordance with the Global Toggle Switch model for 7TM receptor activation.

Ghrelin receptor inverse agonists: identification of an active peptide core and its interaction epitopes on the receptor.

[D-Arg1,D-Phe5,D-Trp7,9,Leu11]Substance P functions as a low-potency antagonist but a high-potency full inverse agonist on the ghrelin receptor. Through a systematic deletion and substitution analysis of this peptide, the C-terminal carboxyamidated pentapeptide wFwLX was identified as the core structure, which itself displayed relatively low inverse agonist potency. Mutational analysis at 17 selected positions in the main ligand-binding crevice of the ghrelin receptor demonstrated that ghrelin apparently interacts only with residues in the middle part of the pocket [i.e., between transmembrane (TM)-III, TM-VI and TM-VII]. In contrast, the inverse agonist peptides bind in a pocket that extends all the way from the extracellular end of TM-II (AspII:20) across between TM-III and TM-VI/VII to TM-V and TM-IV. The potency of the main inverse agonist could be improved up to 20-fold by a number of space-generating mutants located relatively deep in the binding pocket at key positions in TM-III, TM-IV and TM-V. It is proposed that the inverse agonists prevent the spontaneous receptor activation by inserting relatively deeply across the main ligand-binding pocket and sterically blocking the movement of TM-VI and TM-VII into their inward-bend, active conformation. The combined structure-functional analysis of both the ligand and the receptor allowed for the design of a novel, N-terminally Lys-extended analog of wFwLL, which rescued the high-potency, selective inverse agonism that was dependent upon both AspII:20 and GluIII:09. The identified pharmacophore can possibly serve as the basis for targeted discovery of also nonpeptide inverse agonists for the ghrelin receptor.

Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling.

Two nonpeptide (L692,429 and MK-677) and two peptide [GH-releasing peptide (GHRP)-6 and ghrelin] agonists were compared in binding and in signal transduction assays: calcium mobilization, inositol phosphate turnover, cAMP-responsive element (CRE), and serum-responsive element (SRE) controlled transcription, as well as arrestin mobilization. MK-677 acted as a simple agonist having an affinity of 6.5 nm and activated all signal transduction systems with similar high potency (0.2-1.4 nm). L-692,429 also displayed a very similar potency in all signaling assays (25-60 nm) but competed with a 1000-fold lower apparent affinity for ghrelin binding and surprisingly acted as a positive allosteric receptor modulator by increasing ghrelin's potency 4- to 10-fold. In contrast, the potency of GHRP-6 varied 600-fold (0.1-61 nm) depending on the signal transduction assay, and it acted as a negative allosteric modulator of ghrelin signaling. Unexpectedly, the maximal signaling efficacy for ghrelin was increased above what was observed with the hormone itself during coadministration with the nonendogenous agonists. It is concluded that agonists for the ghrelin receptor vary both in respect of their intrinsic agonist properties and in their ability to modulate ghrelin signaling. A receptor model is presented wherein ghrelin normally only activates one receptor subunit in a dimer and where the smaller nonendogenous agonists bind in the other subunit to act both as coagonists and as either neutral (MK-677), positive (L-692,429), or negative (GHRP-6) modulators of ghrelin function. It is suggested that an optimal drug candidate could be an agonist that also is a positive modulator of ghrelin signaling.