A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

Peripheral nerve injuries can result in lifelong disability. Primary coaptation is the treatment of choice when the gap between transected nerve ends is short. Long nerve gaps seen in more complex injuries often require autologous nerve grafts or nerve conduits implemented into the repair. Nerve grafts, however, cause morbidity and functional loss at donor sites, which are limited in number. Nerve conduits, in turn, lack an internal scaffold to support and guide axonal regeneration, resulting in decreased efficacy over longer nerve gap lengths. By comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into nanofibers, which can be aligned to mimic the native architecture of peripheral nerve. As such, they represent a potential substrate for use in a bioengineered nerve graft substitute. To examine this, we cultured Schwann cells with bioactive PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate within the biomaterial. Next, we devised a PA construct for use in a peripheral nerve critical sized defect model. Rat sciatic nerve defects were created and reconstructed with autologous nerve, PLGA conduits filled with various forms of aligned PAs, or left unrepaired. Motor and sensory recovery were determined and compared among groups. Our results demonstrate that Schwann cells are able to adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor and sensory function in animals treated with conduit/PA constructs comparable to animals treated with autologous nerve grafts. Functional recovery in conduit/PA and autologous graft groups was significantly faster than in animals treated with empty PLGA conduits. Histological examinations also demonstrated increased axonal and Schwann cell regeneration within the reconstructed nerve gap in animals treated with conduit/PA constructs. These results indicate that PA nanofibers may represent a promising biomaterial for use in bioengineered peripheral nerve repair.     

Efficacy of preoperative portal vein embolization prior to major hepatectomy for patients with impaired liver function: A retrospective study

Hepatocellular carcinoma (HCC) is often associated with chronic liver disease, such as hepatitis or cirrhosis, and this association may limit the use of surgery as a therapy, and if surgery is pursued, may give rise to postoperative hepatic failure. We evaluated the outcome in patients with HCC given preoperative portal vein embolization (PVE) before they underwent major hepatectomy. After PVE, portal pressure increased significantly. Two weeks after PVE, both the volume of the non-embolized lobe and the 15-min indocyamine green retention rate (ICG R15) were significantly increased. The prognostic score, calculated on the basis of age, ICG R15, and the resection rate, was significantly decreased. The operative mortality rate was significantly lower in patients who underwent PVE before surgery than in patients who did not receive PVE. The cumulative survival rate of the PVE patients, even those with cirrhosis of the liver, was significantly higher. Prior PVE appears to allow more extensive major hepatectomy and to lessen the risk of this invasive surgery. However, patients in whom the portal pressure immediately after PVE was more than 30cm H₂O and/or whose prognostic score exceeded 50 points developed postoperative hepatic failure. These features should be kept in mind when it is decided whether surgery is indicated. Nevertheless, preoperative PVE appears to be a beneficial procedure for patients undergoing major hepatectomy, particularly those with chronic liver disease.     

Clinicopathologic Features and Outcome After Liver Resection for Hepatocellular Carcinoma in Patients with Concurrent Versus Previous Chronic Hepatitis B

Purpose We compared the clinicopathologic features affecting outcome after surgery for hepatocellular carcinoma (HCC) between patients with concurrent and previous chronic hepatitis B.Methods Group A consisted of 58 patients with concurrent chronic hepatitis B, defined by seropositivity for the hepatitis B surface antigen (HBsAg), and group B consisted of 18 patients whose HCC was detected after disappearance of the HBsAg. We assessed the influence of various characteristics on outcome.Results The mean age and percentage of patients suffering from alcohol abuse or diabetes mellitus were significantly greater in group B than in group A, whereas histologic hepatitis activity, hepatic fibrosis, and alanine aminotransferase activity were significantly lower in group B than in group A. The tumor-free survival rates were similar between the two groups, but the risk factors of recurrence differed. In group A, relative youth, high aspartate aminotransferase activity, low platelet count, multiple tumors, large tumor size, portal invasion, cirrhosis, nonanatomic resection, and positive surgical margin were risk factors. In group B, large tumor size and poor differentiation were risk factors.Conclusion Hepatitis B status, tumor factors, and the type of operation affected cancer recurrence after surgery for HCC in patients with concurrent chronic HBV, as opposed to only tumor factors in patients with previous chronic hepatitis B.     

Accuracy and precision of a system for assessing severity of tooth wear

PURPOSE: The purpose of this study was to introduce a computer-assisted quantitative tooth wear-analyzing system and test its accuracy and precision. MATERIALS AND METHODS: An image of a horizontally projected dental arch was captured, and the facet area of each tooth was calculated using a digital image analyzer. For normalization, the facet area of the individual tooth was divided by the total area of the corresponding tooth; this result was the tooth wear score. The accuracy and precision of this method were determined through the intraclass correlation coefficient using 10 dental casts. Tooth wear on the dental casts of 50 subjects was actually measured. RESULTS: The accuracy of the tooth wear score determined by a newly trained examiner was greater than 0.85 of the intraclass correlation coefficient; this was tested against the score determined by consensus of three experienced examiners. The reproducibility within a 1-week interval was also greater than 0.85. With regard to the tooth wear score from 50 sets of dental casts, the distribution of tooth wear was generally consistent with data reported in the literature. CONCLUSION: The results suggest that the newly trained examiner can exhibit adequate accuracy and precision after appropriate training in identifying tooth wear facets. Recorded data from 50 subjects added face validity to this new system.     

Increased prevalence of bisphosphonate‐related osteonecrosis of the jaw with vitamin D deficiency in rats

Necrotic bone exposure in the oral cavity has recently been reported in patients treated with nitrogen‐containing bisphosphonates as part of their therapeutic regimen for multiple myeloma or metastatic cancers to bone. It has been postulated that systemic conditions associated with cancer patients combined with tooth extraction may increase the risk of osteonecrosis of the jaw (ONJ). The objective of this study was to establish an animal model of bisphosphonate‐related ONJ by testing the combination of these risk factors. The generation of ONJ lesions in rats resembling human disease was achieved under the confluence of intravenous injection of zoledronate (ZOL; 35 µg/kg every 2 weeks), maxillary molar extraction, and vitamin D deficiency [VitD(?)]. The prevalence of ONJ in the VitD(?)/ZOL group was 66.7%, which was significantly higher (p < .05, Fisher exact test) than the control (0%), VitD(?) (0%), and ZOL alone (14.3%) groups. Similar to human patients, rat ONJ lesions prolonged the oral exposure of necrotic bone sequestra and were uniquely associated with pseudoepitheliomatous hyperplasia. The number of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–biotin nick‐end label–positive (TUNEL⁺) osteoclasts significantly increased on the surface of post–tooth extraction alveolar bone of the VitD(?)/ZOL group, where sustained inflammation was depicted by [¹⁸F]fluorodeoxyglucose micro‐positron emission tomography (µPET). ONJ lesions were found to be associated with dense accumulation of mixed inflammatory/immune cells. These cells, composed of neutrophils and lymphocytes, appeared to juxtapose apoptotic osteoclasts. It is suggested that the pathophysiologic mechanism(s) underpinning ONJ may involve the interaction between bisphosphonates and compromised vitamin D functions in the realm of skeletal homeostasis and innate immunity. © 2010 American Society for Bone and Mineral Research     

Laparoscopic liver resection for treating recurrent hepatocellular carcinoma

Background

It is still unknown whether laparoscopic liver resection is suitable for recurrent hepatocellular carcinoma (HCC) after previous curative hepatic resection.

Method

The perioperative outcomes of 40 patients treated with second surgery for recurrent HCC by partial hepatectomy were studied retrospectively. The second surgery was performed under laparotomy in 20 patients (laparotomy group) and under laparoscopy in 20 patients (laparoscopy group).

Results

Intraoperative blood loss (p < 0.0001) and the incidence of postoperative complications (p = 0.0004) were lower in the laparoscopy group than in the laparotomy group. The incidence rates of surgical site infection and intractable ascites were significantly higher in the laparotomy group than in the laparoscopy group (p = 0.0202, p = 0.0436, respectively). The proportion of patients classified as Clavien grade IIIa was higher in the laparotomy group than in the laparoscopy group (p = 0.0033). The duration of the postoperative hospital stay was significantly shorter in the laparoscopy group than in the laparotomy group (p < 0.0001).

Conclusions

Postoperative morbidity has been decreased by the introduction of laparoscopic liver resection in patients with recurrent HCC after curative hepatic resection. As a result, the duration of the postoperative stay is shorter.     

Recent progress in laparoscopic liver resection

Laparoscopic liver resection has been performed in a limited number of centers, but worldwide the adoption and worldwide progress of the procedure have been slow since the 1990s, mainly because of the difficulty of controlling the hemorrhage during dissection of the hepatic parenchyma. In the late 2000s, technological innovations, improvement in surgical technique, and surgeons' accumulation of experience have led to more rapid progress of laparoscopic liver resection. Now, laparoscopic liver resection is able to be done by several approaches, for all locations of the tumors, for several diseases, with several types of resection, not only for tumors but for liver transplantation, with equivalent or better results compared with open surgery. Laparoscopic liver resection has been a standard procedure for left lateral sectionectomy or peripheral resection of the anterior liver, and other types of laparoscopic liver resection are expected to be standard in the near future.