Acute pancreatitis: animal models and recent advances in basic research

Acute pancreatitis (AP) is characterized by edema, acinar cell necrosis, hemorrhage, and severe inflammation of the pancreas. Patients with AP present with elevated blood and urine levels of pancreatic digestive enzymes, such as amylase and lipase. Severe AP may lead to systemic inflammatory response syndrome and multiorgan dysfunction syndrome, which account for the high mortality rate of AP. Although most (>80%) cases of AP are associated with gallstones and alcoholism, some are idiopathic. Although the pathogenesis of AP has not yet been elucidated, a common feature is the premature activation of trypsinogen within pancreatic tissues, which triggers autodigestion of the gland. Recent advances in basic research suggest that etiologic factors including cyclooxygenase-2, substance P, and angiotensin II may have novel roles in this disease. Basic research data obtained thus far have been based on animal models of AP ranging from mild edematous pancreatitis to severe necrotizing pancreatitis. In view of this, an adequate selection of experimental animal models is of paramount importance. Notwithstanding these animal models, it should be emphasized that none of these models mimic the clinical situation where varying degrees of severity usually occur. In this review, commonly used animal models of AP will be critically evaluated. A discussion of recent advances in our knowledge about AP risk factors is also included.     

Evaluation of vascular complications of pancreas transplantation with high-spatial-resolution contrast-enhanced MR angiography

PURPOSE: To retrospectively evaluate high-spatial-resolution contrast material-enhanced three-dimensional (3D) magnetic resonance (MR) angiography for assessment of vascular complications of pancreas allografts. MATERIALS AND METHODS: The institutional review board approved the study and waived the requirement for informed patient consent owing to the retrospective nature of the study with use of an anonymous-subject database. The study was HIPAA compliant. The clinical and MR angiography findings in 11 patients (eight men, three women; mean age, 43 years; age range, 30-54 years) who had a history of pancreatic transplant dysfunction and underwent a total of 13 contrast-enhanced 3D MR angiography examinations were retrospectively reviewed. Comparison with conventional angiography findings was possible for four MR angiography examinations, comparison with surgical findings was possible for two examinations, and clinical follow-up was possible for all examinations. Two observers in consensus and blinded to the clinical results performed image analysis of the arterial and venous segments. Classification agreement was assessed with quadratic weighted kappa statistics. RESULTS: Ten MR angiography examinations revealed vascular complications or signs suggestive of rejection. Only three examinations were considered to have completely normal results. All major complications were detected and included complete or partial arterial graft occlusion, stenosis of the arterial Y-graft caused by a kink, complete venous thrombosis, and arteriovenous fistula with pseudoaneurysm formation. For 46 arterial segments and 15 venous segments with angiographic and/or surgical comparison, overall agreement with MR angiography findings was nearly perfect (mean kappa, 0.983; standard error of the mean, 0.128). CONCLUSION: High-spatial-resolution MR angiography of pancreas allografts enables assessment of the arterial and venous vascular anatomy and can be used to reliably identify clinically relevant vascular complications.     

Feasibility of using interpolated contours of targets and organs at risk in intensity-modulated radiation therapy treatment planning for advanced-stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity-modulated radiation therapy (IMRT) for advanced T-stage nasopharyngeal carcinoma. The present study focused on T3-T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5-mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full-scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

Towards a near-zero recurrence rate in laparoscopic inguinal hernia repair for pediatric patients of all ages

Background/Purpose

The recurrence rate in laparoscopic inguinal hernia (LIH) repair remains high. The aim of this study was to assess whether the introduction of technical improvements, including (1) decreasing tension on the purse-string knot when closing the internal hernia opening by injecting normal saline extraperitoneally, (2) using an airtight knot, and (3) stress-testing the airtightness of the knot by increasing intraperitoneal gas pressure, could eliminate recurrence in LIH repair in pediatric patients of all ages.

Methods

A retrospective review was performed of the prospectively collected data of 451 LIH repairs in 314 children of various ages in our institution from September 2002 to September 2006. The technical improvements mentioned above to prevent recurrence were introduced in the second half of the series of operations (tensionless repair [TL]). The data on both groups of operations were then compared.

Results

A total of 225 hernias were repaired in the first group (164 patients), compared with 226 in the TL group (150 patients). The differences between the ratio of boys to girls (129:35 vs 112:38) and the mean ages (50.84 ± 48.15 vs 45.59 ± 47.95 m) in the 2 groups were not statistically significant. The recurrence rate in the TL group was much lower than in the first group (0.4% vs 4.88%, P = .003). There was no postoperative testicular atrophy in either group of patients.

Conclusion

It is possible to achieve a near-zero recurrence rate in laparoscopic hernia repair in pediatric patients of all ages.     

Roles of Neutrophil Gelatinase-Associated Lipocalin in Continuous Ambulatory Peritoneal Dialysis-Related Peritonitis

Introduction  We measured the neutrophil gelatinase-associated lipocalin (NGAL) concentration in peritoneal dialysate effluent (PDE) collected following an acute episode of continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. Results  NGAL concentration in PDE increased in the first 3 days after developing peritonitis and correlated well with the neutrophil count. In patients with culture-negative peritonitis, the NGAL in PDE was lower than that in patients with gram-positive or gram-negative peritonitis. Apart from providing additional diagnostic support to bacterial-induced peritonitis, measurement of NGAL in PDE may be useful to differentiate the neutrophil-dependent culture-negative peritonitis from that associated with non-bacterial or non-cellular etiologies. Conclusion  Human peritoneal mesothelial cell (HPMC) is another source of NGAL during peritonitis. NGAL was specifically induced in HPMC by IL-1β. Incubation of HPMC with recombinant NGAL reversed the transforming growth factor-β-induced up-regulation of Snail and vimentin but rescued the down-regulation of E-cadherin. Our data suggest that NGAL may exert a protective effect in modulating the epithelial-to-mesenchymal transition activated following peritonitis.     

Outbreak of Intestinal Infection Due to Rhizopus microsporus

Sinopulmonary and rhinocerebral zygomycosis has been increasingly found in patients with hematological malignancies and bone marrow transplantation, but intestinal zygomycosis remains very rare in the literature. We investigated an outbreak of intestinal infection due to Rhizopus microsporus in 12 patients on treatment for hematological malignancies over a period of 6 months in a teaching hospital. The intake of allopurinol during hospitalization (P < 0.001) and that of commercially packaged ready-to-eat food items in the preceding 2 weeks (P < 0.001) were found to be independently significant risk factors for the development of intestinal zygomycosis. A total of 709 specimens, including 378 environmental and air samples, 181 food samples, and 150 drug samples, were taken for fungal culture. Among them, 16 samples of allopurinol tablets, 3 prepackaged ready-to-eat food items, and 1 pair of wooden chopsticks were positive for Rhizopus microsporus, which was confirmed by ITS1-5.8S-ITS2 rRNA gene cluster (internal transcribed spacer [ITS]) sequencing. The mean viable fungal counts of allopurinol obtained from wards and pharmacy were 4.22 × 10³ CFU/g of tablet (range, 3.07 × 10³ to 5.48 × 10³) and 3.24 × 10³ CFU/g of tablet (range, 2.68 × 10³ to 3.72 × 10³), respectively, which were much higher than the mean count of 2 × 10² CFU/g of food. Phylogenetic analysis by ITS sequencing showed multiple clones from isolates of contaminated allopurinol tablets and ready-to-eat food, of which some were identical to patients'' isolates, and with one isolate in the cornstarch used as an excipient for manufacture of this drug. We attempted to type the isolates by random amplification of polymorphic DNA analysis, with limited evidence of clonal distribution. The primary source of the contaminating fungus was likely to be the cornstarch used in the manufacturing of allopurinol tablets or ready-to-eat food. Rhizopus microsporus is thermotolerant and can multiply even at 50°C. The long holding time of the intermediates during the manufacturing process of allopurinol amplified the fungal load. Microbiological monitoring of drugs manufactured for highly immunosuppressed patients should be considered.Zygomycosis has become an important emerging infection in patients with hematological malignancy undergoing chemotherapy or bone marrow transplantation (24), especially with the availability of voriconazole as antifungal prophylaxis (25, 28, 44). Breakthrough zygomycosis in patients on voriconazole prophylactic treatment is usually manifested as sinopulmonary or rhinocerebral disease, since the fungal spores are ubiquitously found in the environment and could therefore be acquired through inhalation or traumatic inoculation through the skin or mucosa. Gastrointestinal zygomycosis has been a rare clinical entity (50, 54), but cases or outbreaks of tongue, gastric, or cutaneous zygomycosis due to Rhizopus microsporus after exposure to contaminated wooden tongue depressors have been reported (23, 26, 33).The Rhizopus microsporus species group, which belongs to the class Zygomycetes and the order Mucorales, can cause life-threatening infections in immunocompromised patients (9, 39, 46). The laboratory diagnosis of R. microsporus relies mainly on the characteristic microscopic and phenotypic features of the fungal mycelium culture on agar medium. A molecular diagnostic test for this fungus is not widely available. PCR amplification and sequencing of the 18S and 28S rRNA genes (58, 64), internal transcribed spacer (ITS) region of rRNA (27), and recently PCR restriction fragment length polymorphism (22) and high-affinity iron permease gene sequence have been used to identify members of the clinically important Zygomycetes (30).Here we report an unprecedented outbreak of intestinal zygomycosis due to R. microsporus as a result of the oral intake of contaminated allopurinol tablets and ready-to-eat food items in patients with hematological malignancies undergoing chemotherapy and bone marrow transplantation. The clinical spectrum of this outbreak of intestinal infection by R. microsporus ranges from asymptomatic colonization to mucosal involvement to invasive disease.     

Ethyl-cyanoacrylate is acutely nontoxic and provides sufficient bond strength for anastomosis of peripheral nerves

Anastomosis is a common technique for the union of severed nerve trunks. This is commonly performed with sutures, a process that can be both time consuming and injurious to tissue. One promising alternative to suturing is the use of adhesives to join the severed segments. Cyanoacrylate-based glues have been used clinically as a surgical adhesive for soft tissues. However, the acute effects of these glues on nerve electrophysiology and the tensile strength of the rejoined tissues have not been evaluated. Using a guinea pig model, we analyzed the mechanical properties of transected sciatic nerves repaired with epineural application of ethyl-cyanoacrylate and the short term consequences of cyanoacrylate application on impulse conduction. Results showed that nerves coapted with ethyl-cyanoacrylate were capable of bearing in vivo forces. Additionally, no acute effects on conduction were observed in uninjured sciatic nerves exposed to ethyl-cyanoacrylate. In conjunction with long term in vivo reports from literature, the current results support the use of cyanoacrylates in nerve repair.