Bone cancer pain: The effects of the bisphosphonate alendronate on pain, skeletal remodeling, tumor growth and tumor necrosis

Patients with metastatic breast, lung or prostate cancer frequently have significant bone cancer pain. In the present report we address, in a single in vivo mouse model, the effects the bisphosphonate alendronate has on bone cancer pain, bone remodeling and tumor growth and necrosis. Following injection and confinement of green fluorescent protein-transfected murine osteolytic tumor cells into the marrow space of the femur of male C3H/HeJ mice, alendronate was administered chronically from the time the tumor was established until the bone cancer pain became severe. Alendronate therapy reduced ongoing and movement-evoked bone cancer pain, bone destruction and the destruction of sensory nerve fibers that innervate the bone. Whereas, alendronate treatment did not change viable tumor burden, both tumor growth and tumor necrosis increased. These data emphasize that it is essential to utilize a model where pain, skeletal remodeling and tumor growth can be simultaneously assessed, as each of these can significantly impact patient quality of life and survival.Peer reviewe

Simultaneous reduction in cancer pain, bone destruction, and tumor growth by selective inhibition of cyclooxygenase-2

More than half of all chronic cancer pain arises from metastases to bone, and bone cancer pain is one of the most difficult of all persistent pain states to fully control. Several tumor types including sarcomas and breast, prostate, and lung carcinomas grow in or preferentially metastasize to the skeleton where they proliferate, and induce significant bone remodeling, bone destruction, and cancer pain. Many of these tumors express the isoenzyme cycloxygenase-2 (COX-2), which is involved in the synthesis of prostaglandins. To begin to define the role COX-2 plays in driving bone cancer pain, we used an in vivo model where murine osteolytic 2472 sarcoma cells were injected and confined to the intramedullary space of the femur in male C3HHeJ mice. After tumor implantation, mice develop ongoing and movement-evoked bone cancer pain-related behaviors, extensive tumor-induced bone resorption, infiltration of the marrow space by tumor cells, and stereotypic neurochemical alterations in the spinal cord reflective of a persistent pain state. Thus, after injection of tumor cells, bone destruction is first evident at day 6, and pain-related behaviors are maximal at day 14. A selective COX-2 inhibitor was administered either acutely [NS398; 100 mg/kg, i.p.] on day 14 or chronically in chow {MF. tricyclic; 0.015%, p.o.} from day 6 to day 14 after tumor implantation. Acute administration of a selective COX-2 inhibitor attenuated both ongoing and movement-evoked bone cancer pain, whereas chronic inhibition of COX-2 significantly reduced ongoing and movement-evoked pain behaviors, and reduced tumor burden, osteoclastogenesis, and bone destruction by >50%. The present results suggest that chronic administration of a COX-2 inhibitor blocks prostaglandin synthesis at multiple sites, and may have significant clinical utility in the management of bone cancer and bone cancer pain.Supported by NIH Grants from the National Institute of Neurologic Disorders and Stoke (NS23970), the National Institute for Drug Abuse (DA11986), National Institute of Dental and Craniofacial Research Dentist Scientist Award (DSA) DE00270, Training Grant DE07288, and a Merit Review from the Veterans Administration.Peer reviewe

Reconstruction Techniques after Proctectomy: What's the Best?

There are ~40,000 new rectal cancer cases diagnosed each year in the United States, representing the second most common gastrointestinal malignancy (behind colon cancer). With the advent of sphincter preserving techniques, patients with mid and low colorectal cancers enjoy the benefits of better postoperative functional outcomes and quality of life; however, controversy exists over which reconstructive technique is superior in restoring bowel continuity. Construction of a straight coloanal anastomosis is technically simpler, but functional outcomes are inferior compared with colonic reservoirs. The purpose of this review is to summarize the current data regarding reconstructive techniques following proctectomy

Is there a role for simultaneous hepatic and colorectal resections? A contemporary view from NSQIP

The optimal timing of primary and metastatic tumor management in patients with synchronous hepatic colorectal metastases remains controversial. We aimed to compare perioperative outcomes of simultaneous colorectal/liver resection (SCLR) with isolated resections utilizing a national clinical database