Nucleotide metabolic mismatches in mammalian hearts: implications for transplantation

Introduction

Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR.

Methods

We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro).

Results

E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001).

Conclusions

This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.     

Laminar flow reduces cases of surgical site infections in vascular patients

Introduction

Numerous strategies are employed routinely in an effort to lower rates of surgical site infections (SSIs). A laminar flow theatre environment is generally used during orthopaedic surgery to reduce rates of SSIs. Its role in vascular surgery, especially when arterial bypass grafts are used, is unknown.

Methods

A retrospective review of a prospectively maintained database was undertaken for all vascular procedures performed by a single consultant over a one-year period. Cases were performed, via random allocation, in either a laminar or non-laminar flow theatre environment. Demographic data, operative data and evidence of postoperative SSIs were noted. A separate subgroup analysis was undertaken for patients requiring an arterial bypass graft. Univariate and multivariate logistical regression was undertaken to identify significant factors associated with SSIs.

Results

Overall, 170 procedures were analysed. Presence of a groin incision, insertion of an arterial graft and a non-laminar flow theatre were shown to be predictive of SSIs in this cohort. In the subgroup receiving arterial grafts, only a non-laminar flow theatre environment was shown to be predictive of an SSI.

Conclusions

This study suggests that laminar flow may reduce incidences of SSI, especially in the subgroup of patients receiving arterial grafts.     

Staging of Adenocarcinoma of the Esophagogastric Junction: Comparison of AJCC 6th and 7th Gastric and 7th Esophageal Staging Systems

Background

Adenocarcinoma of esophagogastric junction (EGJ) is currently staged by the esophageal staging criteria according to the American Joint Committee on Cancer (AJCC) staging system, 7th edition. We compared the performance of 6th gastric (G6), 7th gastric (G7), and 7th esophageal (E7) staging systems.

Methods

A total of 202 curatively resected adenocarcinomas of EGJ were analyzed. Patient outcomes were assessed according to G6, G7, and E7 staging. Tumor invasion to the subserosal or serosa layer was regarded as invasion to the adventitia for E7 staging. Performance was measured based on monotonicity (decreasing survival with increasing stage), distinctiveness (survival difference between different stages), and homogeneity (homogenous survival in the same stage).

Results

Each staging system was monotonous except for T1-2N0 lesions of E7. This was related to the introduction of histologic grade in E7 staging. Distinctiveness in each staging system was variable. As for the homogeneity, patients whose disease was staged as Ib (E7) exhibited different survival when reassessed by G6 and G7; again, this was related to histologic grading. Patients with IIIb (G7) and IIIc (E7) disease had different survival when reassessed by G6 staging, reflecting the poorer survival of patients with more than 15 lymph node metastases.

Conclusions

Staging of EGJ cancer based on the current AJCC, 7th edition, criteria of esophageal cancer staging has several limitations. We recommend considering modifications of the following in future updates of the staging system: accurate anatomical definition of tumor depth, removal of histologic grade from staging parameters, and classification of more than 15 lymph node metastases as a highly advanced stage.     

Robot-assisted Posterior Retroperitoneoscopic Adrenalectomy Using Single-port Access: Technical Feasibility and Preliminary Results

Background

Posterior retroperitoneoscopic adrenalectomy (PRA) has several benefits compared with transperitoneal adrenalectomy in that it is safe and has a short learning curve. In addition, it provides direct short access to the target organ, prevents irritation to the intraperitoneal space, and does not require retraction of adjacent organs.1 ^– 3 We have performed several cases of robot-assisted PRA using single-port access for small adrenal tumors. This multimedia article introduces the detailed methods and preliminary results of this procedure.

Methods

Five patients underwent single-port robot-assisted PRA between March 2010 and June 2011 at our institution. During the procedure, patients were placed in a prone jackknife position with their hip joints bent at a right angle (Fig. 1). A 3 cm transverse skin incision was made just below the lowest tip of the 12th rib (Fig. 2), and the Glove port (Nelis, Kyung-gi, Korea) was placed through the skin incision while maintaining pneumoretroperitoneum (Fig. 3). CO₂ was then insufflated to a pressure of 18 mm Hg to create an adequate working space. A 10 mm robotic camera with a 30-degree up view was placed at the center of the incision through the most cephalic portion of the Glove port. A Maryland dissector or Prograsp forceps (Intuitive Surgical, Inc., Sunnyvale, CA) was placed on the medial side of the incision, and Harmonic curved shears (Intuitive Surgical) were placed on the lateral side of the incision (Fig. 4). Using the Maryland dissector and the harmonic curved shears, the Gerota fascia is opened, perinephric fat is dissected, and the kidney upper pole is mobilized to expose the adrenal gland (Fig. 5). Gland dissection starts with lower margin detachment from the upper kidney pole in a lateral to medial direction (Fig. 6). After dissecting the adrenal gland from surrounding adipose tissue and medial isolation of the adrenal central vein, the vessel is ligated with a 5 mm hemolock clip (Fig. 7). Patient clinicopathologic data were analyzed retrospectively.

Results

The mean patient age was 56.6 ± 8.7 (range, 47–69) years. Right and left side approaches were used in two and three patients, respectively. All cases were adrenal cortical adenoma. The mean tumor size was 1.48 ± 0.28 (range, 1.0–1.7) cm. The mean surgery duration (skin to skin) was 159.4 ± 57.6 (range, 103–245) minutes, and the mean estimated blood loss was 46.0 ± 56.8 (range, 5–120) ml. The average time to oral intake and postoperative hospital stay were 0.65 ± 0.11 (range, 0.54–0.79) days and 4.0 ± 2.23 (range, 3–8) days, respectively. There were no conversions to open surgery or postoperative compli- cations.

Discussion

Some trials of minimally invasive single-access surgery of the adrenal gland have recently been performed.4 ^, 5 However, these new techniques have several limitations as a result of restrictions on instrumentation movement because of the small access ports used and relatively low-quality images produced. The recent introduction of the da Vinci S surgical robot system (Intuitive Surgical) to endoscopic surgery has improved instrumental dexterity and provided the surgeon with an ergonomically designed operating system. This system is also potentially safer and more meticulous in performing operations than endoscopic procedures as a result of a 3-D, magnified, stable operative view.6 ^, 7 The advantages of the da Vinci S surgical robot system and the numerous benefits of the posterior retroperitoneal approach motivated us to utilize single-port robot-assisted PRA. The primary selection criteria were small tumor size and a minimal amount of periadrenal fatty tissue because robot-assisted PRA using single-port access provides a small operative space, which causes manipulation problems when tumors are large. To ensure the safe application of these new techniques, we recommend that novice surgeons begin using single-port robot-assisted PRA for smaller tumors < 2 cm in patients with a body mass index of < 30 kg/m², gradually extending the size and body mass index as they accumulate experience. Although robot-assisted PRA using single-port access could not be compared with the other robotic adrenalectomy techniques in this study, the potential advantages of this approach compared to conventional robot-assisted transperitoneal adrenalectomy include a reduction in postoperative ileus, bacterial contamination, and intestinal complications because the peritoneal cavity is not opened, in addition to a reduction in postoperative pain because of its minimally invasive nature.

Conclusions

Our initial experiences with robot-assisted PRA using single-port access assured us of its safety and feasibility for the resection of small adrenal tumors. Although single-port robot-assisted PRA appears to be safe and feasible, further experience and research is required to optimize patient selection criteria and verify its advantages over the traditional three-incision PRA technique.     

Quantitative Shear Wave Elastography as a Prognostic Implication of Papillary Thyroid Carcinoma (PTC): Elasticity Index Can Predict Extrathyroidal Extension (ETE)

Objective

To investigate whether the quantitative elasticity index of shear wave elastography (SWE) can predict extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) preoperatively.

Methods

A total of 208 patients with pathology confirmed PTC whom underwent SWE during preoperative staging US between April 2011 to June 2012 were included.SWE indices of E _mean, E _max, E _min of the index malignancy, the ratios between E _mean of the lesion and parenchyma (E _ratio-P), and muscle (E _ratio-M), and grayscale US findings, including ETE, multifocality, bilaterality, and central and lateral lymph node (LN) metastasis were evaluated. The correlations of SWE indices and grayscale US findings with pathologic prognostic factors of PTC were analyzed by Chi square or Fisher’s exact test, and multivariate regression analysis.

Results

ETE was associated with E _mean, E _max, E _min, and E _ratio-M (P = 0.005, 0.009, 0.016 and <0.001, respectively), multifocality was associated with E _mean, E _max, and E _min (P = 0.028, 0.007, and 0.004, respectively), and central LN metastasis was associated with E _ratio-M (P = 0.03). On multivariate analysis, E _mean and E _min were independent factors for predicting ETE (P = 0.032, 0.049, respectively).

Conclusions

Quantitative elasticity index of SWE could predict pathologic ETE, and SWE could be a complimentary method to grayscale US for preoperative prediction of prognostic factors of PTC.     

Prognostic Value of Early Postoperative Tumor Marker Response in Gastric Cancer

Background

The clinical usefulness of tumor markers as predictors of treatment outcome in patients with stomach cancer after radical gastrectomy has been poorly defined. The purpose of this study was to evaluate a comprehensive understanding of the impact of early postoperative tumor marker normalization on survival after gastrectomy.

Methods

Between January 2001 and December 2007, we enrolled 206 patients who had received radical gastrectomy as an initial treatment and had elevated carcinoembryonic antigen (CEA) (>5 ng/mL) or carbohydrate antigen (CA) 19-9 (>37 U/mL) levels. Early tumor marker response was defined as a normalization of preoperative CEA or CA19-9 values 1–2 months after gastrectomy.

Results

The mean patient age was 61 years (range 29–84 years), and 139 patients (67.5 %) were male. Early tumor marker response was identified in 150 of 206 (72.8 %) patients. Of the patients, 49 (23.8 %), 41 (19.9 %), and 116 (56.4 %) were stages I, II, and III, respectively, according to the seventh edition of the American Joint Commission on Cancer (AJCC) staging system. Both disease-free survival (DFS) and overall survival (OS) were significantly longer in patients with tumor marker response compared with nonresponse (61.5 vs. 37.6 months; P = 0.010 and 71.3 vs. 50.9 months; P = 0.008, respectively). Multivariate analyses showed that high CA19-9 level, early tumor marker response, and tumor, node, metastasis classification system stage were independent predictors of DFS and OS (P < 0.05).

Conclusions

Early CEA or CA19-9 normalization after radical gastrectomy is a strong prognostic factor for gastric cancer, especially in patients with high preoperative levels of tumor markers.     

Analysis of high-voltage electrical spinal cord injury using diffusion tensor imaging

The aim of this study was to investigate spinal cord injury (SCI) on the basis of diffusion tensor imaging (DTI) in patients with high-voltage electrical injury. We recruited eight high-voltage electrical injury patients and eight healthy subjects matched for age and sex. DTI and central motor conduction time were acquired in both the patient and control groups. We obtained DTI indices according to the spinal cord levels (from C2 to C7) and cross-section locations (anterior, lateral, and posterior). Fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between the two groups; additionally, they were compared in relation to spinal cord level and cross-section location. In the patient group relative to the control group, the FA value decreased and the MD and RD values increased in all of the regions of interest (ROI) with statistical significance (p < 0.05). In the patient group, particularly in the ROIs of the anterior spinal cord compared with the lateral and posterior spinal cords, the FA value decreased with statistical significance (p < 0.05). The DTI indices did not differ by level. DTI revealed the change of diffusion in the spinal cords of patients with high-voltage electrical injury, and corroborated the pathophysiology, myelinopathy and typical anterior spinal cord location of high-voltage electrical SCI already reported in the literature.