Financial Value Analysis of Surgical Residency Programs: An Argument Against Replacement.

OBJECTIVE: To quantify the replacement cost of patient care provided by surgical residents and build a Graduate Medical Education (GME) value analysis model. DESIGN: Our Graduate Medical Education Executive Steering Committee designed a resident replacement cost model, based on patient care hours (adjusted for educational activities and a clinical efficiency factor, differential cost of faculty supervision for residents vs. APPs, and current program financials (revenue minus expenses). Strategic value planning included: academic productivity (local and national conference presentations, book chapters and publications and Senior Staff recruitment and retention. SETTING: Department of Surgery at Baylor Scott & White Medical Center, a tertiary institution located in Temple, TX. PARTICIPANTS: Our replacement model was applied to a sample 30-position residency program. RESULTS: Modeling a 30-position residency program, replacement cost approaches 4.5 million dollars, based on a 1:3 Senior Staff-to-APP replacement ratio. A complete APP replacement complement has a projected cost of 3.1 million dollars, while replacement with Senior Staff approaches 9 million dollars. CONCLUSIONS: We present a novel model for residency value analysis allowing for reproducible and standardized results across multiple residency programs. Challenges inherent to GME, such as clinical efficiency and the cost of faculty supervision, are accounted for. Quantifying resident replacement cost and financial value is a powerful tool when discussing institutional workforce planning within the current financial climate of healthcare.

The evidence for single-incision laparoscopic colectomy: is it time to adopt?

Laparoscopic colorectal surgery has advantages over open surgery including shorter postoperative length of hospital stay, early return of bowel function, decreased complications and reduced postoperative pain. Innovative minimally invasive surgery techniques such as single-incision laparoscopic surgery (SIL) have emerged to further enhance outcomes of conventional laparoscopy. This technique uses a single small incision for access of all instruments and specimen extraction. This concept has been proposed to improve cosmesis and enhance recovery. Technological advances have been introduced to overcome the challenges of co-axial instrument movement and collision that is inherent to SIL surgery. The application of SIL techniques to colorectal surgery is in its infancy, but gaining significant momentum. Early case reports and series have shown feasibility and safety. Emerging comparative studies of SIL colectomy to standard laparoscopic techniques are providing evidence of equivalency with potential benefit in outcomes such as reduced early postoperative pain and shortened length of hospital stay. The application of the SIL platform to robotics and transanal surgery demonstrates the broadening scope of this innovative field. However, we must be cognizant of the impact on surgeon training and resident education. In this review we present the current evidence supporting the application of SIL to colorectal surgery.

Salvage abdominoperineal resection after failed Nigro protocol: modest success, major morbidity.

OBJECTIVE: Chemotherapy and radiation (C-XRT) is the first-line therapy for epidermoid carcinomas of the anal canal (ECAC). Treatment failure occurs in up to 33% of patients. Salvage-abdominoperineal resection (APR) is the treatment of choice for locoregional failure but pre-operative radiation may increase wound complications. The purpose of this study was to evaluate patient survival and wound complications after salvage-APR for C-XRT failure. METHODS: We reviewed the clinical records of all patients who failed initial C-XRT for ECAC diagnosed between 1992 and 2002. We evaluated patient demographics, treatment, tumour characteristics, survival and postoperative complications. RESULTS: Nineteen patients were identified. The mean age at diagnosis was 55 years. Eight (42%) patients had persistent disease; 11 (58%) had tumour recurrence. APR was performed in 15 patients. Perineal wound complications occurred in 12 (80%) patients; half were major complications. Primary flap reconstruction at time of APR was performed in 5 (33%) patients; 2 experienced major wound complications. Overall-survival after salvage APR was 40% (6/15) and disease-free survival was 47% (7/15) at a median follow-up of 14 months (range 2-95 months). Recurrence after salvage-APR occurred in 7 (47%) patients at a median follow-up of 5 months (range 3-19 months). Kaplan-Meier survival analysis showed an advantage for recurrent over persistent disease with 2-year and 5-year survival rates of 75%vs 34% and 28%vs 0%, respectively. CONCLUSIONS: Failure of C-XRT for ECAC is associated with a poor prognosis. Although salvage APR may be curative in some patients, perineal wound complications are frequent and primary flap reconstruction is not reliable.

De novo colorectal cancer: five-year survival is markedly lower in transplant recipients compared with the general population.

INTRODUCTION: The biological behavior of most solid tumors in transplant recipients has not been adequately compared to the general population. The purpose of the present study was to compare outcomes in de novo colorectal cancer (CRC) following solid organ transplantation to those observed in the general population (SEER) database. METHODS: All transplant recipients with de novo CRC in the Israel Penn International Transplant Tumor Registry were identified and analyzed and the data were compared to CRC patients in the SEER National Cancer Institute (NCI) database. RESULTS: One hundred and fifty transplant recipients with de novo CRC were identified, among which were 93 (62%) kidney, 29 (19.3%) heart, 27 (18%) liver, and 1 (0.7%) lung recipients. Median age of transplant recipients was 54 years, compared to a median age of 72 years for patients in the SEER NCI database. However, compared to patients from the SEER NCI database, recipients with Duke's A through C stage disease were noted to experience a significant decrease in 5-year survival. The results in Duke's C patients were particularly dismal. CONCLUSIONS: The early age at presentation of CRC in transplant recipients suggests that the development of de novo CRC may be effected by immunosuppression. Decreased 5-year survival rates in transplant recipients compared to the general population suggest that CRC in transplant patients is biologically more aggressive. These data cannot distinguish whether the lower survival rates are because the CRC are inherently biologically more aggressive or whether immunosuppression allows for more aggressive clinical behavior of CRC.

The role of caspases in methotrexate-induced gastrointestinal toxicity.

BACKGROUND: Enterocolitis is the major toxicity of methotrexate-based cancer chemotherapy, which limits its clinical applications. Methotrexate induces gut mucosal apoptosis in vivo; however, little is known about the molecular mechanism involved. The effectors of apoptosis include the caspase family of proteases, which are selectively activated in a stimulus-specific and tissue-specific fashion. The aims of this study were (1) to establish an in vitro model of methotrexate-induced gut apoptosis and (2) to determine the role of caspases in methotrexate-induced apoptosis in intestinal epithelial cells. METHODS: Rat intestinal epithelial cells (RIE-1) were treated with methotrexate in the absence or presence of ZVAD-fluoromethyl ketone, a general caspase inhibitor. Apoptosis was quantified by means of deoxyribonucleic acid (DNA) fragmentation assays and Hoechst nuclear staining. Caspase activation was measured with the use of fluorogenic substrates. RESULTS: Methotrexate induced apoptosis and decreased cell number in RIE-1 cells. DNA fragmentation was preceded by the sequential activation of caspases 9, 2, and 3, whereas caspases 1 and 8 remained inactive. ZVAD-fluoromethyl ketone inhibited methotrexate-induced caspase activation, DNA fragmentation, and nuclear condensation. CONCLUSIONS: These results indicate that methotrexate activates specific caspases and induces apoptosis in RIE-1 cells. Furthermore, caspases may play an important role in methotrexate-induced apoptosis in RIE-1 cells and may be potential therapeutic targets to attenuate methotrexate-induced enterocolitis.

Prevention of mucosal atrophy: role of glutamine and caspases in apoptosis in intestinal epithelial cells.

Glutamine starvation induces apoptosis in enterocytes; therefore glutamine is important in the maintenance of gut mucosal homeostasis. However, the molecular mechanisms are unknown. The caspase family of proteases constitutes the molecular machinery that drives apoptosis. Caspases are selectively activated in a stimulus-specific and tissue-specific fashion. The aims of this study were to (1) identify specific caspases activated by glutamine starvation and (2) determine whether a general caspase inhibitor blocks glutamine starvation-induced apoptosis in intestinal epithelial cells. Rat intestinal epithelial (RIE-1) cells were deprived of glutamine. Specific caspase activation was measured using fluorogenic substrate assay. Apoptosis was quantified by DNA fragmentation and Hoechst nuclear staining. Glutamine starvation of RIE-1 cells resulted in the time-dependent activation of caspases 3 (10 hours) and 2 (18 hours), and the induction of DNA fragmentation (12 hours). Caspases 1 and 8 remained inactive ZVAD-fluoromethyl ketone, a general caspase inhibitor, completely blocked glutamine starvation-induced caspase activation, DNA fragmentation, and nuclear condensation. These results indicate that glutamine starvation selectively activates specific caspases, which leads to the induction of apoptosis in RIE-1 cells. Furthermore, inhibition of caspase activity blocked the induction of apoptosis, suggesting that caspases are potential molecular targets to attenuate apoptotic responses in the gut.

Targeting molecular pathways with camptothecin as novel therapy for gastric cancer.

Novel chemotherapeutic agents are needed to treat gastric cancer for which the prognosis remains dismal. The antitumor alkaloid camptothecin (CPT) may be useful in the treatment of certain solid tumors; however, its effects on gastric cancer are largely undefined. The purpose of our study was to characterize the effects of CPT on human gastric tumors in vivo and to determine the cellular mechanisms involved in CPT-mediated inhibition. Two human gastric cancers, WIL and TOR, were transplanted subcutaneously into athymic nude mice. After tumors reached 50 to 100 mm(2), mice were randomized into three groups to receive injections of either low-dose CPT (5 mg/kg), high-dose CPT (10 mg/kg), or vehicle (control) intraperitoneally 3 days a week for 3 weeks. Tumors were measured and weighed, and protein levels of the cell cycle inhibitor, p21Waf1/Cip1, and the antiapoptotic protein, Bcl-2, were assessed. Both dosages of CPT significantly inhibited growth of WIL and TOR gastric tumors. CPT (10 mg/kg) reduced tumor size compared to baseline, establishing this as a tumoricidal dosage. Treatment with CPT was associated with increased levels of p21Waf1/Cip1 and decreased levels of Bcl-2. CPT effectively kills human gastric cancers associated with increased levels of p21Waf1/Cip1 and decreased levels of Bcl-2. By activating cell cycle withdrawal and cell death through induction of p21Waf1/Cip1 and downregulation of Bcl-2, CPT may be an effective agent for gastric cancer.

Inhibition of gastric cancer by camptothecin involves apoptosis and multiple cellular pathways.

BACKGROUND: The prognosis for gastric cancer remains dismal; novel agents that target specific molecular pathways are needed as adjuvant therapy. Camptothecin (CPT), on inhibitor of topoisomerase I, is effective in the treatment of certain solid tumors; its effects on gastric cancer are largely undefined. The purpose of this study was to (1) characterize the effects of CPT on the growth of a human gastric cancer and (2) assess potential cellular mechanisms responsible for CPT-mediated growth inhibition. METHODS: The human gastric cancer SIIA was transplanted subcutaneously into athymic nude mice. After tumors reached approximately 100 mm2, mice were randomized into 3 groups to receive either CPT (5 or 10 mg/kg) or vehicle (control) intraperitoneally 3 days per week for 3 weeks; tumor size was measured biweekly. To assess potential mechanisms of CPT-mediated inhibition, SIIA cells were treated with CPT (20 mumol/L) and cells were counted over a time course; apoptosis was assessed by Hoechst stain and DNA laddering. Expression of p53 (a tumor suppressor), p21Waf1 and p27Kip1 (cell cycle inhibitors), and Bcl-2 and Bcl-XL (antiapoptotic proteins) was determined. RESULTS: CPT (5 and 10 mg/kg) significantly inhibited tumor growth of SIIA gastric cancers compared with controls. CPT-mediated inhibition of SIIA cell proliferation was associated with an increase in apoptosis. Moreover, CPT treatment resulted in induction of p53, p21Waf1, and p27Kip1 and a decrease in Bcl-2 and Bcl-XL RNA and protein levels. CONCLUSIONS: Treatment with CPT effectively inhibited the growth of the human gastric cancer SIIA; the mechanism involved was induction of apoptosis mediated by up-regulation of p53, p21Waf1/Cip1, and p27Kip1 and the down-regulation of Bcl-2 and Bcl-XL. Novel agents such as CPT, which target specific molecular pathways, may prove clinically useful in the adjuvant treatment of gastric cancers.

A novel cytotoxic agent for human carcinoid tumors.

BACKGROUND: Conventional adjuvant therapy for advanced carcinoid tumors remains disappointing; novel therapeutic agents are needed. We have shown previously that inhibiting polyamine biosynthesis with alpha-difluoromethylornithine (DFMO) slows the growth of carcinoid tumors. However, the clinical utility of DFMO has been limited by its cytostatic property. Synthetic polyamine analogs such as 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) appear to be cytotoxic against several human tumors. The purpose of our study was to determine whether BE-4-4-4-4 is a more effective antiproliferative and cytotoxic agent than DFMO on human carcinoid (BON) cells in vitro. METHODS: BON cells were treated with either 5 mmol/L DFMO, 0.5 to 10 mumol/L BE-4-4-4-4, or vehicle (control). Ornithine decarboxylase activity was determined by the rate of 14CO2 production, and intracellular polyamine levels were determined by chromatography. Cell number and viability were determined by Coulter counter and trypan blue exclusion, respectively. RESULTS: BE-4-4-4-4 inhibited ornithine decarboxylase activity and depleted all 3 polyamines. BE-4-4-4-4 decreased cell numbers by 81% compared with control and 27% compared with DFMO. BE-4-4-4-4 also induced a 2-fold increase in cell death compared with control or DFMO. CONCLUSIONS: BE-4-4-4-4 is cytotoxic and more effective than DFMO in inhibiting growth of BON cells. Polyamine analogs such as BE-4-4-4-4 may be effective adjuvant therapeutic agents for advanced carcinoid tumors.

Glutamine deprivation induces apoptosis in intestinal epithelial cells.

BACKGROUND: Glutamine is the most abundant amino acid in the blood, and its deprivation leads to gut mucosal atrophy. The small intestinal mucosa is maintained by a balance between cell proliferation and cell death by apoptosis. We reported that glutamine is required for nitrogen-stimulated proliferation in intestinal epithelial cells. We do not know whether glutamine regulates apoptosis in the gut. The purpose of this study is to determine whether glutamine deprivation induces apoptosis in rat intestinal epithelial (RIE-1) cells and to compare the effect of glutamine starvation with that of methionine and cysteine (Met/Cys) starvation. METHODS: RIE-1 cells were deprived of either glutamine or Met/Cys for 24 hours. Cell numbers were determined by cell counting and tetrazolium enzymatic assay. Apoptosis was quantified by Annexin V assay and confirmed by DNA gel electrophoresis and Hoecsht nuclear staining. RESULTS: Deprivation of glutamine or Met/Cys resulted in decreased cell numbers. However, only the glutamine-deprived group showed significant induction of apoptosis with increased Annexin V staining, DNA laddering, and nuclear condensation. CONCLUSIONS: This study provides biochemical and morphologic evidence that glutamine deprivation induces apoptosis in rat intestinal epithelial cells. In contrast, Met/Cys starvation suppresses cell number without induction of apoptosis. These results suggest that glutamine serves as a specific survival factor in enterocytes.

The effect of early versus late fasciotomy in the management of extremity trauma.

BACKGROUND: Recent reports have demonstrated an increase in the number of complications associated with delayed timing of fasciotomy for trauma. This study examines the effectiveness of early (less than 12 hours) versus late (more than 12 hours) fasciotomy in the injured extremity. METHODS: This is a retrospective review of 88 patients undergoing fasciotomy for extremity trauma admitted to the University of Cincinnati from January 1990 through December 1995. Records were reviewed for demographics, compartment pressures, time and type of fasciotomy, complications, limb salvage, and mortality. Statistical analysis was determined with chi-squared, multivariant regression analysis, and Student's t test with significance at p less than 0.05. RESULTS: Sixty-one (69%) patients had fasciotomy performed before 12 hours and twenty-seven (31%) after 12 hours. Although the rates of infection differed significantly between the two groups (7.3% for early versus 28% for late), the rates of limb salvage and neurologic sequelae were similar. Age, mechanism, shock, associated injuries, and time to fasciotomy were not predictive of complications. CONCLUSIONS: Fasciotomy for trauma is most efficacious when performed early. However, when performed late, it results in similar rates of limb salvage as compared with early fasciotomy but at the increased risk of infection. These results support aggressive use of fasciotomy in extremity trauma regardless of time of diagnosis.

Clinical experience with BioMedicus centrifugal ventricular support in 172 patients.

One hundred and seventy-two patients at The Methodist Hospital in Houston, Texas, were placed on BioMedicus centrifugal ventricular support. One hundred thirty-nine patients were male and 33 were female with a mean age of 59.7 years. Reasons for support were postcardiotomy cardiac failure (129 patients), cardiac allograft failure (17 patients), bridge to transplantation (10 patients), resuscitation (7 patients), postpercutaneous transluminal coronary angioplasty emergent (2 patients), and other (7 patients). Support was by left ventricular assist device in 108 patients, right ventricular assist device in 20 patients, and biventricular assist device in 44 patients. Eighty-four patients (48.8%) were weaned from the ventricular assist device, and 88 patients (51.2%) were not weaned. Thirty-four patients (20.0%) were discharged from the hospital. Complications included coagulopathy, renal insufficiency/failure, respiratory insufficiency/failure, neurological deficits, sepsis, arrhythmias, and device-related complications. Overall causes of death were ventricular failure (55.1%), triage (13.0%), arrhythmias (9.4%), graft failure (5.9%), coagulopathy (4.3%), sepsis syndrome (2.9%), device-related (0.7%), and other (0.7%). BioMedicus centrifugal ventricular support can be implemented rapidly and easily. Device-related complications are few (1.2%), and it is relatively inexpensive when compared with other ventricular assist systems. This series demonstrates that a substantial number of patients may benefit from temporary centrifugal ventricular support.