Inherent or acquired drug resistance, which frequently characterizes cancer cells, is caused by multiple mechanisms, including dysfunctional metabolism of the lipid second messenger ceramide. Ceramide, the basic structural unit of the sphingolipids, plays a role in activating cell death signals initiated by cytokines, chemotherapeutic agents, and ionizing radiation. Recent discoveries about the metabolism of ceramide suggest that this agent may have an important influence on the effectiveness of various cancer therapeutics. In particular, the cytotoxic effect of chemotherapy is decreased when generation of ceramide is impaired but is increased when the degradation of ceramide is blocked. Herein, we review the mechanisms of resistance to chemotherapeutic agents in terms of ceramide metabolism.
External hemipelvectomy has low mortality but high morbidity. Postoperative wound infection and flap necrosis are multifactorial events related to length and extent of operation. Level of vascular ligation strongly influenced flap necrosis rate for posterior flap hemipelvectomy.
Excision and unroofing procedures were effective treatments with infrequent complications and low recurrence rates. Well-planned surgical treatment aiming to remove or unroof the area of intractable hidradenitis suppurativa was highly effective in the management of this challenging disease.
Hemipelvectomy is associated with high wound morbidity. When the hemipelvectomy flap has a musculocutaneous design, hernias are exceedingly rare. Although immediate reconstruction is accomplished with a hemipelvectomy flap in the vast majority of cases, secondary reconstructions are often required for management of wound complications. For large defects, a contralateral inferiorly based rectus abdominis muscle or musculocutaneous flap is the reconstruction of choice. The rectus abdominis muscle should therefore always be preserved in hemipelvectomy patients by careful preoperative planning, especially when creation of an ostomy is considered.
Margin-negative excision of the MCC remains the mainstay of treatment. Surgical staging, preferably with SLND, identifies patients that may develop regional recurrence. This study further supports the important role of adjuvant radiation therapy in improving locoregional tumor control in the patients with MCC.
Although flap coverage is an established treatment for radiated wounds, STSG in conjunction with liberal utilization of VAC therapy is an alternative for selected patients where acceptable soft tissue bed is preserved. Healing of the preoperatively radiated wounds can be achieved in the vast majority of such patients with minimal need for additional reconstructive operations.
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