Lisfranc and Chopart amputation: A systematic review.

BACKGROUND: Lisfranc and Chopart amputations are historically controversial procedures. To obtain evidence for the pros and cons we performed a systematic review to analyze wound healing, the need for re-amputation at a higher level, and ambulation after a Lisfranc or Chopart amputation. METHODS: A literature search was performed in 4 databases (Cochrane, Embase, Medline, and PsycInfo), using database-specific search strategies. Reference lists were studied to include relevant studies that were missed in the search. Of the 2881 publications found, 16 studies could be included in this review. Excluded publications concerned editorials, reviews, letters to the editor, no full text available, case reports, not meeting the topic, and written in a language other than English, German, or Dutch. RESULTS: Failed wound healing occurred in 20% after Lisfranc amputation, in 28% after modified Chopart amputation, and 46% after conventional Chopart amputation. After Lisfranc amputation, 85% of patients were able to ambulate without prosthesis for short distances, and after modified Chopart 74%. After a conventional Chopart amputation, 26% (10/38) had unlimited household ambulation. CONCLUSIONS: The need for re-amputation because wound healing problems occurred most frequently after conventional Chopart amputation. All 3 types of amputation levels do, however, provide a functional residual limb, with the remaining ability to ambulate without prosthesis for short distances. Lisfranc and modified Chopart amputations should be considered before proceeding to a more proximal level of amputation. Further studies are needed to identify patient characteristics to predict favorable outcomes of Lisfranc and Chopart amputations.

Angiogenesis in synchronous and metachronous colorectal liver metastases: the liver as a permissive soil.

OBJECTIVE: Resection of a primary colorectal carcinoma (CRC) can be accompanied by rapid outgrowth of liver metastases, suggesting a role for angiogenesis. The aim of this study is to investigate whether the presence of a primary CRC is associated with changes in angiogenic status and proliferation/apoptotic rate in synchronous liver metastases and/or adjacent liver parenchyma. METHODS: Gene expression and localization of CD31, HIF-1α, members of the vascular endothelial growth factor (VEGF) and Angiopoietin (Ang) system were studied using qRT-PCR and immunohistochemistry in colorectal liver metastases and nontumorous-adjacent liver parenchyma. Proliferation and apoptotic rate were quantified. Three groups of patients were included: (1) simultaneous resection of synchronous liver metastases and primary tumor (SS-group), (2) resection of synchronous liver metastases 3 to 12 months after resection of the primary tumor [late synchronous (LS-group)], and (3) resection of metachronous metastases >14 months after resection of the primary tumor (M-group). RESULTS: In all 3 groups a higher expression of the angiogenic factors was encountered in adjacent liver parenchyma as compared to the metastases. VEGFR-2 gene expression was abundant in adjacent liver parenchyma in all 3 groups. VEGF-A and VEGFR-1 were prominent in adjacent parenchyma in the SS-group. The SS-group showed the highest Ang-2/Ang-1 ratio both in the metastases and the adjacent liver. This was accompanied by a high turnover of tumor cells. CONCLUSION: In the presence of the primary tumor, the liver parenchyma adjacent to the synchronous liver metastases provides an angiogenic prosperous environment for metastatic tumor growth.

COX-2 Inhibition Combined with Radiation Reduces Orthotopic Glioma Outgrowth by Targeting the Tumor Vasculature.

Cyclooxygenase 2 (COX-2) inhibitors have been shown to enhance tumor's response to radiation in several animal models. The strong association of COX-2 and angiogenesis suggests that the tumor vasculature may be involved in this process. The current study investigated whether treatment with the COX-2 inhibitor E-6087 could influence response to local radiation in orthotopically growing murine gliomas and aimed to analyze the involvement of the tumor vasculature. GL261 glioma cells were injected into the cerebrum of C57bl/6 mice. From day 7 after tumor cell injection, mice were treated with COX-2 inhibitor at 50 mg/kg i.p. every third day. Radiation consisted of three fractions of 2 Gy given daily from day 9 to day 11. Mice were killed at day 21. The COX-2 inhibitor significantly enhanced the response to radiation, reducing mean volume to 32% of tumors treated with radiation only. The combination treatment neither increased apoptosis of tumor cells or stromal cells nor affected tumor microvascular density. In vitro, E-6087 and its active metabolite did not affect clonogenic survival of GL261 cells or human umbilical vein endothelial cell after radiation. In vivo, however, there was a nonsignificant increase in Angiopoietin (Ang)-1 and Tie-2 mRNA levels and a decrease of Ang-2 mRNA levels after combination treatment. These changes coincided with a significant increase in alpha-smooth muscle actin-positive pericyte coverage of tumor vessels. In conclusion, the antitumor effect of radiation on murine intracranial glioma growth is augmented by combining with COX-2 inhibition. Our findings suggest an involvement of the tumor vasculature in the observed effects.