Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastases--activation of cell invasion and migration pathways.

Elucidating the mechanism of liver tumor growth and metastasis after hepatic ischemia-reperfusion (I/R) injury of a small liver remnant will lay the foundation for the development of therapeutic strategies to target small liver remnant injury, and will reduce the likelihood of tumor recurrence after major hepatectomy or liver transplantation for liver cancer patients. In the current study, we aimed to investigate the effect of hepatic I/R injury of a small liver remnant on liver tumor development and metastases, and to explore the precise molecular mechanisms. A rat liver tumor model that underwent partial hepatic I/R injury with or without major hepatectomy was investigated. Liver tumor growth and metastases were compared among the groups with different surgical stress. An orthotopic liver tumor nude mice model was used to further confirm the invasiveness of the tumor cells from the above rat liver tumor model. Significant tumor growth and intrahepatic metastasis (5 of 6 vs. 0 of 6, P=0.015), and lung metastasis (5 of 6 vs. 0 of 6, P=0.015) were found in rats undergoing I/R and major hepatectomy compared with the control group, and was accompanied by upregulation of mRNA levels for Cdc42, ROCK (Rho kinase), and vascular endothelial growth factor, as well as activation of hepatic stellate cells. Most of the nude mice implanted with liver tumor from rats under I/R injury and major hepatectomy developed intrahepatic and lung metastases. In conclusion, hepatic I/R injury of a small liver remnant exacerbated liver tumor growth and metastasis by marked activation of cell adhesion, invasion, and angiogenesis pathways.     

Sclerostin Antibody Treatment Increases Bone Formation,Bone Mass,and Bone Strength in a Rat Model of Postmenopausal Osteoporosis

The development of bone‐rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long‐standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl‐AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six‐month‐old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency‐induced bone loss, at which point Scl‐AbII was administered for 5 wk. Scl‐AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency‐induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non‐ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody‐mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone‐related disorders, such as postmenopausal osteoporosis.     

Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats

The current report describes the skeletal effects of a sclerostin monoclonal antibody (Scl-AbIII) treatment at a yellow (fatty) marrow skeletal site in adult female rats. Ten-month-old female Sprague–Dawley rats were treated with vehicle or Scl-AbIII at 5 or 25 mg/kg, twice per week by s.c. injection for 4 weeks. Trabecular bone from a yellow (fatty) marrow site, the 5th caudal vertebral body (CVB), was processed undecalcified for quantitative bone histomorphometric analysis. Compared to vehicle controls, Scl-AbIII at both doses significantly increased bone formation parameters and trabecular bone volume and thickness and decreased bone resorption parameter in the trabecular bone of the CVB. As a reference, we also found that the Scl-AbIII at both doses significantly decreased bone resorption and increased bone formation and bone volume in a red (hematopoietic) marrow site, the 4th lumber vertebral body (LVB). It appears that the percentage of increase in trabecular bone volume induced by Scl-AbIII treatment was slightly larger in the LVB than in the CVB. In summary, these preclinical findings show that antibody-mediated sclerostin inhibition has significant bone anabolic effects at both red and yellow marrow skeletal sites.     

Effect of reverse shoulder design philosophy on muscle moment arms

This study analyzes the muscle moment arms of three different reverse shoulder design philosophies using a previously published method. Digital bone models of the shoulder were imported into a 3D modeling software and markers placed for the origin and insertion of relevant muscles. The anatomic model was used as a baseline for moment arm calculations. Subsequently, three different reverse shoulder designs were virtually implanted and moment arms were analyzed in abduction and external rotation. The results indicate that the lateral offset between the joint center and the axis of the humerus specific to one reverse shoulder design increased the external rotation moment arms of the posterior deltoid relative to the other reverse shoulder designs. The other muscles analyzed demonstrated differences in the moment arms, but none of the differences reached statistical significance. This study demonstrated how the combination of variables making up different reverse shoulder designs can affect the moment arms of the muscles in different and statistically significant ways. The role of humeral offset in reverse shoulder design has not been previously reported and could have an impact on external rotation and stability achieved post‐operatively. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:605–613, 2015.     

Infected femoral artery pseudoaneurysm in drug addicts: the beneficial use of the internal iliac artery for arterial reconstruction

BACKGROUND: Infected femoral artery pseudoaneurysm (IFAP) is a severe complication in parenteral drug abusers, with difficult and controversial management. Ligation alone without revascularization is frequently associated with later intermittent claudication and limb amputation. Furthermore, arterial reconstruction with a synthetic or venous conduit is limited because of a contaminated field and, often, unavailability of autologous venous grafts. In this study, we present our experience with the internal iliac artery (IIA) as a graft for arterial reconstruction after IFAP excision in these patients. METHODS: Data of 14 consecutive patients who presented with IFAP secondary to parenteral drug abuse from 2001 to 2005 were analyzed. Twelve patients (85.7%) were male. The median age was 27 years (range, 19-42 years). In 13 cases, the IFAP involved the common femoral artery, and in 1 case it involved the profunda femoris artery (PFA). In nine patients, we used the IIA for arterial reconstruction (five as a patch and four as an interposition graft), whereas in two patients the arterial deficit was repaired with a great saphenous vein patch. In two cases, an extra-anatomic bypass with a synthetic polytetrafluoroethylene graft was performed. In one patient, the pseudoaneurysm involved the PFA and was treated with excision and ligation of the PFA. RESULTS: All nine patients who underwent revascularization with the use of IIA were free of claudication symptoms. None of them experienced any perioperative complications, had signs of reinfection, or required limb amputation during the follow-up period (median, 19 months; range, 4-52 months). Regarding the remaining five patients, one died 25 days after surgery because of multiorgan failure, and one underwent reoperation because of proximal anastomotic rupture of a synthetic graft. The latter patient finally underwent a transmetatarsal amputation. CONCLUSIONS: The use of IIA for arterial reconstruction after IFAP excision in drug abusers is safe and effective. These preliminary results indicate that the implementation of this technique offers many advantages compared with traditional treatment options.     

Endovascular repair of late abdominal aortic aneurysm rupture owing to mixed-type endoleak following endovascular abdominal aortic aneurysm repair

We report the successful endovascular repair of a ruptured abdominal aortic aneurysm (AAA) in a multimorbid patient 8 months after endovascular abdominal aortic aneurysm repair (EVAR). A 74-year-old man with a history of EVAR 8 months earlier presented with hypotension, severe back pain, and tenderness on abdominal palpation. A contrast-enhanced computed tomographic scan showed a large retroperitoneal hematoma and confirmed the diagnosis of secondary abdominal aortic rupture. Because the patient had severe comorbidities, the endovascular method was chosen for further management. Two stent grafts were placed appropriately to eliminate a type 1a and a type 3 endoleak owing to modular separation of the left iliac graft limb from the main body stent graft. An additional self-expanding stent was deployed in the solitary right renal artery to open its origin, which was partially overlapped by the proximal cuff. The patient was discharged on the tenth postoperative day and is alive and well 1 year postoperatively. This case indicates that endovascular repair is feasible not only in cases of primarily ruptured AAAs but also in secondarily ruptured AAAs after failure of EVAR.     

Comparison of Clinicopathologic Factors in 122 Patients with Resected Pancreatic and Ileal Neuroendocrine Tumors from a Single Institution

Background  

Recent population-based studies have demonstrated significant differences in outcome between patients with pancreatic and ileal neuroendocrine tumors. The objective of this study was to examine the clinicopathologic differences between ileal and pancreatic neuroendocrine tumors following resection.     

Surgical resection of locally recurrent renal cell carcinoma after nephrectomy: Oncological outcome and predictors of survival

Objective

To describe the course of disease of patients surgically treated for locally recurrent renal cell carcinoma (LRRCC) after nephrectomy and to identify potential predictive factors for long-term survival.