Is the progression free survival advantage of concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin in patients with advanced cervical cancer worth the additional cost? A cost-effectiveness analysis.

OBJECTIVE: The objective of this study is to determine whether concurrent and adjuvant chemoradiation with gemcitabine/cisplatin is cost-effective in patients with stage IIB to IVA cervical cancer. METHODS: A cost-effectiveness model compared two arms of the trial performed by Duenas-Gonzalez et al. [1]: concurrent and adjuvant chemoradiation with gemcitabine/cisplatin (RT/GC+GC) versus concurrent radiation with cisplatin (RT/C). Major adverse events (AEs) and progression free survival (PFS) rates of each arm were incorporated in the model. AEs were defined as any hospitalization including grade 4 anemia, grade 4 neutropenia, and death. Medicare data and literature review were used to estimate costs. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were calculated. Sensitivity analyses were performed for pertinent uncertainties. RESULTS: For 10,000 women with locally advanced cervical cancer, the cost of therapy and AEs was $173.9 million (M) for RT/C versus $259.8M for RT/GC+GC. There were 879 additional 3-year progression-free survivors in the RT/GC+GC arm. The ICER for RT/GC+GC was $97,799 per PF-LYS. When the rate of hospitalization was equalized to 4.3%, the ICER for RT/GC+GC exceeded $80,000. The resultant ICER when increasing PFS in the RT/GC+GC arm by 5% was $62,605 per PF-LYS. When the cost of chemotherapy was decreased by 50%, the ICER was below $50,000 at $41,774 per PF-LYS. CONCLUSIONS: Radiation and gemcitabine/cisplatin for patients with stage IIB to IVA cervical cancer are not cost-effective. The increased financial burden of radiation with gemcitabine/cisplatin and associated toxicities appears to outweigh the benefit of increased 3-year PFS and is primarily dependent on chemotherapy drug costs.

Is selective lymphadenectomy more cost-effective than routine lymphadenectomy in patients with endometrial cancer?

OBJECTIVE: The objective of this study is to determine the cost-effectiveness of two strategies in women undergoing surgery for newly diagnosed endometrial cancer. METHODS: A decision analysis model compared two surgical strategies: 1) routine lymphadenectomy independent of intraoperative risk factors or 2) selective lymphadenectomy for women with high or intermediate risk tumors based on intraoperative assessment including tumor grade, depth of invasion, and tumor size. Published data were used to estimate the outcomes of stage, adjuvant therapy, and recurrence. Costs of surgery, radiation, and chemotherapy were estimated using Medicare Current Procedural Technology codes and Physician Fee Schedule. Cost-effectiveness ratios were estimated for each strategy. Sensitivity analyses were performed including an estimate for lymphedema for patients that underwent a lymphadenectomy. RESULTS: For 40,000 women diagnosed annually with endometrial cancer in the United States, the annual cost of selective lymphadenectomy is $1.14 billion compared to $1.02 billion for routine lymphadenectomy. The selective lymphadenectomy strategy cost an additional $123.3 million. Five-year progression-free survival was 85.9% in the routine strategy compared to 79.3% in the selective strategy. Treatment cost $6349 more per survivor in the selective strategy compared to routine strategy ($36,078 vs. $29,729). These results held up under a variety of sensitivity analyses including costs due to lymphedema which were higher in the routine lymphadenectomy strategy compared to the selective lymphadenectomy strategy ($10 million vs. $7.75 million). CONCLUSIONS: A strategy of selective lymphadenectomy based on intraoperative risk factors for patients with endometrial cancer was less cost-effective than routine lymphadenectomy even when the impact of lymphedema was considered.

Sub-diaphragmatic fascia: role in the recurrence of hiatal hernias.

One of the most common causes of a failed Nissen fundoplication is disruption of the crural repair. We investigated the thickness of the subdiaphragmatic fascia overlying the right and left limb of the right crus in cadavers to determine any difference. Sub-diaphragmatic fascia specimens were obtained from three sites adjacent to the hiatus in 20 preserved cadavers. One square centimeter of fascia was excised 3 cm from the arch of the hiatus on each side and approximately 2-3 mm from the edge of the hiatal opening (labeled RL and LPL). A third sample was taken 1 cm from the arch of the hiatus on the left side (labeled LAL). The thickness of these tissues was measured. The mean tissue thickness of RL, LPL and LAL were 0.22 mm, 0.23 mm and 0.4 mm, respectively. There was no difference in tissue thickness between the lower specimens on both sides (RL vs. LPL); however, LAL was significantly thicker than both RL and LPL (P < 0.05). The thickness of the subdiaphragmatic fascia overlying the right and left limb of the right crus does not differ significantly in the region used for crus closure during antireflux surgery; however, the fascia on the left is thicker anteriorly.

Consequences of elevated homocysteine during embryonic development and possible modes of action.

Elevated maternal homocysteine (Hcys) is a well-established risk factor for embryonic toxicity and the development of congenital defects, particularly neural tube closure defects and neurocristopathies. The mechanisms responsible are unclear but early work has focused on the role of folate metabolism because these defects are greatly reduced by folate supplementation. As a consequence, elevated Hcys is often looked upon as being an indirect consequence of faulty folate metabolism, although more recent studies show Hcys may act directly as a teratogen. Because Hcys is at the crossroads of protein and DNA metabolism, has a propensity to chemically modify proteins directly, can generate free radicals, and even perturb ligand binding to certain receptors, the developmental processes Hcys can potentially disturb are enumerable. But in recent years, investigators have begun identifying cellular and molecular targets for the direct action of Hcys. While elevating Hcys can alter a myriad of basic cellular activities needed for normal development, our current understanding as to the specific etiological mechanisms responsible for congenital defects is very speculative. Here we provide an overview of what is currently known regarding the toxicity and teratogenicity of elevated Hcys during embryonic development, paying particular attention to neural tube and neural crest cell morphogenesis.