Palliative treatments for patients with inoperable gastroesophageal cancers.

Most patients with cancers of the stomach, oesophagus or gastroesophageal junction ultimately develop metastatic or inoperable disease, rendering them incurable. They can, however, benefit from a variety of palliative interventions involving the multidisciplinary team, including chemotherapy, radiotherapy, endoluminal stenting, laser, or surgery. Often a combination of such strategies will be used to control symptoms, and maintain or improve quality of life. In this article, we review these multidisciplinary interventional approaches in patients with gastroesophageal cancers, and highlight future trends.

Molecular pharmacology of cancer therapy in human colorectal cancer by gene expression profiling.

Global gene expression profiling has potential for elucidating the complex cellular effects and mechanisms of action of novel targeted anticancer agents or existing chemotherapeutics for which the precise molecular mechanism of action may be unclear. In this study, decreased expression of genes required for RNA and protein synthesis, and for metabolism were detected in rectal cancer biopsies taken from patients during a 5-fluorouracil infusion. Our observations demonstrate that this approach is feasible and can detect responses that may have otherwise been missed by conventional methods. The results suggested new mechanism-based combination treatments for colorectal cancer and demonstrated that expression profiling could provide valuable information on the molecular pharmacology of established and novel drugs.

One-gland exploration for mediastinal parathyroid adenomas: cervical and thoracoscopic approaches.

BACKGROUND: In patients with sporadic primary hyperparathyroidism, preoperative localization studies may discover a solitary mediastinal parathyroid adenoma. In this circumstance a 1-gland mediastinal exploration, either cervical or thoracoscopic, may be curative. METHODS: In an 18-month period, 5 of 120 consecutive patients underwent an initial 1-gland mediastinal exploration for a solitary mediastinal parathyroid adenoma and 2 patients had a 1-gland mediastinal exploration for persistent hyperparathyroidism. Clinical presentation, imaging studies, surgical techniques, and outcomes were reviewed. RESULTS: Sestamibi scans showed a mediastinal parathyroid adenoma in all 7 patients. Computed tomography provided anatomic localization of middle mediastinal parathyroid adenomas. A cervical approach was used in 4 patients who had a superior mediastinal parathyroid adenoma. Thoracoscopic excision was performed in 3 patients with a middle mediastinal parathyroid adenoma. No complications occurred. Calcium and parathyroid hormone levels normalized in all patients. CONCLUSIONS: Sporadic primary hyperparathyroidism caused by a solitary mediastinal parathyroid adenoma can be treated successfully with 1-gland mediastinal exploration either by a cervical or a thoracoscopic approach as indicated by localization imaging.

Patterns of elevation of plasma 2'-deoxyuridine, a surrogate marker of thymidylate synthase (TS) inhibition, after administration of two different schedules of 5-fluorouracil and the specific TS inhibitors raltitrexed (Tomudex) and ZD9331.

5-Fluorouracil (5-FU) exerts cytotoxic effects through inhibition of thymidylate synthase (TS) and incorporation of metabolites into RNA. TS inhibition may be greater for infusional 5-FU, with bolus regimens more likely to cause RNA effects. Elevation of plasma 2'-deoxyuridine (dUrd) is a surrogate marker of TS inhibition. Nineteen patients were treated with continuous infusion (CI) 5-FU 300mg/m(2)/day or bolus 5-FU 425mg/m(2)/day plus leucovorin (LV) 20mg/m(2)/day days 1-5. Pretreatment (day 1) and day 2, 3, 4, 5, 8, 15, 22, and 29 plasma samples were assayed for dUrd by reverse-phase high-performance liquid chromatography. In patients treated with bolus 5-FU/LV, dUrd elevation at 24 and 48 h was 235 +/- 125 and 254 +/- 119%, respectively, falling to 138 +/- 58%, 156 +/- 89%, and 92 +/- 25% on days 8, 15, and 22, respectively. dUrd elevation with CI 5-FU was 229 +/- 86% at 24 h and 239 +/- 86, 240 +/- 98%, and 255 +/- 109% at days 15, 22, and 29, respectively. Duration of dUrd elevation was generally less than 8 days for bolus 5-FU/LV. A single dose of raltitrexed (3 mg/m(2)) gave a similar profile to this regimen. ZD9331 (130 mg/m(2), days 1 and 8) gave dUrd elevation for 14 of 21 days, with some recovery prior to day 8. Thus, both 5-FU regimens inhibit TS, and prolonged TS inhibition is achieved by CI 5-FU without significant toxicity. This suggests that the mechanism of antiproliferative toxicity from bolus 5-FU/LV is partly non-TS mediated. These results clarify underlying pharmacodynamic processes and could guide scheduling of 5-FU and TS inhibitors.

Endoscopic greater saphenous vein harvesting reduces the morbidity of coronary artery bypass surgery.

BACKGROUND: Most coronary artery bypass grafting (CABG) operations still involve the use of greater saphenous vein (GSV) for one or more grafts, even with the increasing use of arterial conduits for coronary revascularization. Wound complications from GSV harvesting are common, and sometimes severe. In order to reduce the morbidity of this procedure, we adopted a technique of endoscopic vein harvesting (EVH). EVH allows nearly complete harvest of the GSV, with excellent visualization, through minimal incisions. At our institution, a physician's assistant routinely performs EVH, usually while a cardiothoracic surgeon harvests an arterial conduit. In 1997, all GSV harvesting was performed by open technique. During a transition period in 1998 and 1999 we used several different endoscopic techniques. By the beginning of 2000, our technique of EVH was standardized and used routinely. METHODS: To determine whether EVH reduced the morbidity associated with conventional open vein harvesting (OVH), we reviewed the charts of all patients having primary coronary artery bypass operations utilizing GSV during the years 1997 and 2000. RESULTS: The two groups were comparable in risk factors for leg incision complications. The year 2000 EVH group had a marked reduction in the number of wound complications compared with the year 1997 OVH group (7.1% versus 26.1%, P < 0.00001). There were no significant differences between the two groups in total operative time (OVH 224 minutes, EVH 223 minutes, number of distal coronary anastomoses (OVH 3.38 +/- 0.90, EVH 3.38 +/- 0.94), or the rate of clinically apparent early graft failure. There was a significant increase in the use of sequential grafting techniques in the 2000 group (OVH 21.9%, EVH 43.6%, P < 0.00001). CONCLUSIONS: EVH reduced the morbidity associated with GSV harvesting. EVH was associated with an increased use of sequential coronary grafting techniques. EVH does not prolong operative time when performed by experienced personnel. We believe EVH should become the standard of care.

The role of the epidermal growth factor receptor in breast cancer.

Recent trials of drug therapy targeting the erbB receptor HER2 have met with success in breast cancer. The epidermal growth factor receptor or EGFR is a closely related receptor from this same family that is involved in cellular signal transduction and tumor cell growth and survival. Emerging evidence indicates that EGFR is implicated in the development of hormone-resistant breast cancer, and that its activity is intertwined with estrogen receptor. Here, the role of EGFR in breast cancer is reviewed, and data from selected clinical trials of signal transduction inhibition of this cellular target are summarized.