Integrated health systems: success or failure?

There continues to be an increasing number of healthcare delivery systems as a result of marketplace changes that include declining reimbursement and increasing costs for healthcare. However, the majority of these systems fail. Failures are a consequence of poor management, lack of a common mission and business rationale, individual's interests that outweigh the entity's interests, and the conflict of cultures. Incremental changes will continue, but the healthcare environment will remain unstable for the foreseeable future.

The prognostic value of molecular marker analysis in patients treated with trimodality therapy for esophageal cancer.

The purpose of this study was to define the prognostic value of a group of molecular tumor markers in a well-staged population of patients treated with trimodality therapy for esophageal cancer. The original pretreatment paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 118 patients treated with concurrent cisplatin + 5-fluorouracil (5-FU) + 45 Gy radiation followed by resection from 1986 until 1997 at the Duke University Comprehensive Cancer Center. Three markers of possible platinum chemotherapy association [metallothionein (MT), glutathione S-transferase-pi (GST-pi), P-glycoprotein (P-gp or multidrug resistance)] and one marker of possible 5-FU association [thymidylate synthase (TS)] were measured using immunohistochemistry. The median cancer-free survival was 25.0 months, with a significantly improved survival for the 38 patients who had a complete response (P < 0.001). High-level expression of GST-pi, P-gp, and TS were associated with a decreased survival. MT was not significant in this population. Multivariate analysis identified high-level expression in two of the platinum markers (GST-pi and P-gp) and the 5-FU marker TS as independent predictors of early recurrence and death. In conclusion, this investigation measured three possible markers associated with platinum and one possible marker associated with 5-FU in a cohort of esophageal cancer patients. Independent prognostic significance was observed, which suggests that it may be possible to predict which patients may benefit most from trimodality therapy. These data need to be reproduced in a prospective investigation.

Sphincter-sparing treatment for distal rectal adenocarcinoma.

BACKGROUND: Studies suggest that the anal sphincter can be preserved in some patients with distal rectal adenocarcinoma (DRA), but this has not been validated in any prospective multi-institutional trial. METHODS: To test the hypothesis that the anal sphincter can be preserved in some patients with DRA, the Cancer and Leukemia Group B and collaborators reviewed 177 patients who had T1/T2 adenocarcinomas < or = 4 cm in diameter, which encompassed < or = 40% of bowel wall circumference, and were < or = 10 cm from the dentate line. Of the 177 patients, 59 patients who were eligible for the study had T1 adenocarcinomas and received no further treatment; 51 eligible T2 patients received external beam irradiation (5400 cGY/30 fractions 5 days/week) and 5-fluorouracil (500 mg/m2 IV d1-3, d29-31) after local excision. RESULTS: At 48 months median follow-up, 6-year survival and failure-free survival rates of the eligible patients are 85% and 78% respectively. Three patients died of unrelated disease. Two patients were treated for second primary colorectal tumors; both remain disease free (NED). Another eight patients died of disease, four with distant recurrence only. One T1 patient is alive with distant disease. Two T1 and seven T2 patients experienced isolated local recurrences; all underwent salvage abdominoperineal resection (APR). After APR, one T1 and four of seven T2 patients were NED at the time of last visit (2-7 years). One T1 patient died of local and distant disease. Three of seven T2 patients died with distant disease. CONCLUSIONS: We conclude that sphincter preservation can be achieved with excellent cancer control without initial sacrifice of anal function in most patients. After local recurrence, salvage resection appears effective, but longer follow-up time of local and distant disease-free survival is advised before extrapolation to patients with T3 primaries.

Prospectus. Future trends in transfusion.

There are several emerging trends in perioperative transfusion that are promising in terms of clinical practice. These include modifications in transfusion practice, changes in blood bank procedures and philosophy, the use of autologous transfusion methods, and the development of new artificial blood substitutes. Refinement of current techniques will continue, and will be driven by several factors. The most significant recent changes in surgical practice relating to blood transfusion include a decreased reliance on the use of arbitrary transfusion triggers, and the increased use of various forms of autologous transfusion. Other clinical changes have been less obvious, such as changes in blood bank management practice. Similar factors drive the development of blood conservation strategies and artificial blood substitutes or O2 carriers. Both will play a role in reducing perioperative blood loss. The most likely scenarios involve use of blood substitutes in conjunction with various methods of blood conservation. Recent advances in blood banking have made the donor blood supply safer than ever before. Progress in the clinical setting and in the laboratory have widened the possibilities for treatment of perioperative blood loss, with attention to minimizing risk and cost, and maintaining safety for the patient.

Electrical stimulation for idiopathic scoliosis.

To evaluate the effectiveness of lateral electrical spinal stimulation for idiopathic scoliosis, 87 patients treated with this modality were reviewed retrospectively. All patients had no prior treatment, had a documented progression of more than 5 degrees, and were skeletally immature. Forty-seven patients were compliant and followed until skeletal maturity or institution of other treatment. Fifty percent of patients with a high probability of progression required surgery. For compliant patients, 51% progressed 5 degrees or more and 36% progressed 10 degrees or more or required a change to another treatment modality. Statistical analysis demonstrated no significant difference in the probability of progression between this group of treated patients and previously published groups of untreated patients.

Role of mineralocorticoids in adaptation of rabbit cortical collecting duct after loss of renal mass.

The mechanism of compensatory adaptation and hypertrophy of the cortical collecting duct (CCD) was studied by in vitro microperfusion technique after surgical loss of functioning nephrons in the rabbit. Sodium transport was increased at 1 wk (lumen-to-bath sodium transport of 127 +2- 9 vs. 61 +/- 11 pmol.mm-1.min-1 in sham-operated animals, P less than 0.01) and 3 wk (111 +/- 19 vs. 54 +/- 7 pmol.mm-1.min-1, P less than 0.05) but not 16 h (81 +/- 13 vs. 78 +/- 8 pmol.mm-1.min-1) after loss of renal mass. The functional adaptation was accompanied by an increase in the size of the CCD. A rise in plasma aldosterone levels preceded and accompanied the increased sodium transport rate. Adrenalectomy at the time of reduction of renal mass totally prevented the development of both hypertrophy and sodium transport adaptation (sodium transport 15 +/- 8 pmol.mm-1.min-1). When adrenalectomy was combined with clamping the plasma aldosterone level in the nonstressed physiological range, compensatory hypertrophy and adaptation also failed to develop (sodium transport, 66 +/- 10 pmol.mm-1.min-1), but with high-dose aldosterone replacement both the hypertrophy and adaptation of sodium transport (130 +/- 23 pmol.mm-1.min-1) were restored. The results document the importance of increased mineralocorticoid activity in the development of compensatory hypertrophy and adaptation of sodium transport in rabbit CCD after loss of renal mass.

Dissociation of active from immobility components of sexual behavior in female rats by central 6-hydroxydopamine: implications for CA involvement in sexual behavior and sensorimotor responsiveness.

Ovariectomized female rats were given a hormone treatment (2 X 8 micrograms/kg estradiol benzoate) that normally supports only low levels of lordosis responding and no soliciting behavior in tests with sexually active males. When subjected to an intraventricular 6-hydroxydopamine (6-OHDA) procedure (with pargyline pretreatment) that produced 85% and 95% depletions of caudate dopamine and cortical norepinephrine respectively, these females exhibited a dramatic increase in the intensity and frequency of lordotic responding but no soliciting behavior over 3 weekly tests. The increase in lordosis was not due to a drug- or stress-induced release of adrenal progesterone, since dexamethasone suppressed the progesterone levels, as documented by radioimmunoassay, but not the higher receptivity of 6-OHDA treated females. In other ovariectomized females given a hormone regimen (2 X 50 micrograms/kg estradiol benzoate plus 500 micrograms progesterone) that supported maximal levels of lordosis and soliciting, the same 6-OHDA treatment prolonged the average duration of lordosis while actually decreasing the incidence and duration of soliciting. The hypothesis is put forward that the differential effects of interfering with catecholamine, and more likely dopamine function on the soliciting and lordosis components of female sexual behavior might best be understood as a dissociation between mutually antagonistic behavior patterns such that responsiveness involving active orientation and forward locomotion is suppressed, whereas responses requiring immobility are augmented.