Predictors of efficacy and health resource utilization in treatment of complicated intra-abdominal infections: evidence for pooled clinical studies comparing tigecycline with imipenem-cilastatin.

BACKGROUND: Duration of intravenous (IV) treatment, surgical/radiologic interventions for infection control, and hospital length of stay (LOS) are important cost considerations in complicated intra-abdominal infections (cIAIs). METHODS: Data were pooled from two multinational, double-blind studies conducted in hospitalized adults with cIAIs who were randomized (1:1) to receive tigecycline (100 mg IV initial dose then 50 mg IV every 12 h) or imipenem-cilastatin (500 mg IV every 6 h) for 5 to 14 days in order to assess tigecycline safety and efficacy. This report focuses on developing predictors of cure and health care resource utilization, including the need for repeat surgical/radiologic interventions, duration of IV antibiotic therapy, and hospital LOS. Multiple regression models were applied for each of the above outcomes, incorporating both baseline and on-treatment potential covariates. Logistic modeling was used for categorical outcomes (cure; repeat surgical/radiologic interventions) and least squares modeling for continuous outcomes (duration of IV antibiotic therapy; LOS). Stepwise selection was used to retain only those predictors found to be significant (p < 0.05) independent risk factors. RESULTS: The most common causative pathogen was Escherichia coli (63.0%), with 63.3% of the patients exhibiting polymicrobial infections. The most common cIAI diagnosis was complicated appendicitis (51.9%). Lack of clinical cure (+ 6.1 days; p < 0.0001), perforation of the intestine (+3.7 days; p < 0.0001), an Acute Physiology and Chronic Health Evaluation (APACHE) score >15 (+3.1 days; p=0.039), abnormal plasma sodium concentration (+3.7 days; p=0.026), and repeat surgical/radiologic intervention (+2.2 days; p=0.0097) were identified as key risk factors for longer LOS. Inadequate source control was associated with reduced odds of cure, longer IV treatment duration (+1.5 days; p=0.007), and longer LOS. The treatment groups did not differ in terms of LOS, IV treatment duration, or clinical cure. CONCLUSION: Tigecycline was similar to imipenem-cilastatin in terms of both efficacy and health resource utilization. Risk factors identified in this study for both outcome measures are offered as support for guiding clinical practice.

Creation of clinical research databases in the 21st century: a practical algorithm for HIPAA Compliance.

BACKGROUND: Enforcement of the Health Insurance Portability and Accountability Act (HIPAA) began in April, 2003. Designed as a law mandating health insurance availability when coverage was lost, HIPAA imposed sweeping and broad-reaching protections of patient privacy. These changes dramatically altered clinical research by placing sizeable regulatory burdens upon investigators with threat of severe and costly federal and civil penalties. This report describes development of an algorithmic approach to clinical research database design based upon a central key-shared data (CK-SD) model allowing researchers to easily analyze, distribute, and publish clinical research without disclosure of HIPAA Protected Health Information (PHI). METHODS: Three clinical database formats (small clinical trial, operating room performance, and genetic microchip array datasets) were modeled using standard structured query language (SQL)-compliant databases. The CK database was created to contain PHI data, whereas a shareable SD database was generated in real-time containing relevant clinical outcome information while protecting PHI items. Small (< 100 records), medium (< 50,000 records), and large (> 10(8) records) model databases were created, and the resultant data models were evaluated in consultation with an HIPAA compliance officer. RESULTS: The SD database models complied fully with HIPAA regulations, and resulting "shared" data could be distributed freely. Unique patient identifiers were not required for treatment or outcome analysis. Age data were resolved to single-integer years, grouping patients aged > 89 years. Admission, discharge, treatment, and follow-up dates were replaced with enrollment year, and follow-up/outcome intervals calculated eliminating original data. Two additional data fields identified as PHI (treating physician and facility) were replaced with integer values, and the original data corresponding to these values were stored in the CK database. Use of the algorithm at the time of database design did not increase cost or design effort. CONCLUSIONS: The CK-SD model for clinical database design provides an algorithm for investigators to create, maintain, and share clinical research data compliant with HIPAA regulations. This model is applicable to new projects and large institutional datasets, and should decrease regulatory efforts required for conduct of clinical research. Application of the design algorithm early in the clinical research enterprise does not increase cost or the effort of data collection.

Clinical outcomes and fiscal consequences of bilateral neck exploration for primary idiopathic hyperparathyroidism without preoperative radionuclide imaging or minimally invasive techniques.

BACKGROUND: Radionuclide imaging-directed, minimally invasive parathyroid operation is promoted in the surgical literature and public domain as the fastest, most successful, and cheapest means of treating primary idiopathic hyperparathyroidism. The validity of these claims is unproven. This study reviews the treatment outcome results of a large series of patients treated with standard parathyroid operation without preoperative localization studies. Cost comparisons are made between this series and previous reports of selected patients in whom preoperative radionuclide imaging preceded minimally invasive parathyroid operation. METHODS: Diagnosis, treatment, and outcome data for 688 consecutive patients undergoing first neck exploration for primary idiopathic hyperparathyroidism were prospectively collected. All patients in our series underwent standard bilateral neck exploration without preoperative localization studies. Intraoperative methylene blue was used to aid identification of all parathyroid glands. Surgical findings, pathological diagnosis, operative time, length-of-stay, and treatment success data were collected. Cost data were calculated for our series using the identical calculations used in previous reports. Our outcome and calculated cost data were compared with previous reports by centers advocating scan-directed, minimally invasive parathyroid operation. RESULTS: Of 2,752 predicted total glands, 2,520 (91.6%) were identified using standard neck exploration without radionuclide localization studies. Single adenoma, with at least 1 normal gland, was found in 542 patients (78.8%), with 8 in a fifth gland. Multiple-gland hyperplasia was identified in 98 patients (14.2%) and of these 22 (3.2%) were double adenomas. Ten patients had parathyroid carcinoma (1.5%), and all received definitive surgical treatment during the primary operation. Cure rates were assessed by measurement of normal serum calcium and parathyroid hormone levels at 3 and 12 months after operation, and were 97.7% in our series. Mean operating time for the entire series was 65 minutes, decreased to 35 minutes in patients with single adenomas, and mean recovery room time was 30 minutes. Mean total costs for patients undergoing standard exploration for single adenoma was US dollars 1,107, and increased to US dollars 1,243 when patients with multigland disease, hyperplasia, or malignancy were included. CONCLUSIONS: Our series demonstrates operative times and treatment outcomes with costs that are approximately one-third less than those for scan-directed, minimally invasive operation for primary idiopathic hyperparathyroidism. Thus, claims that scan-directed parathyroid operation is the cheapest, fastest, and most successful means of treatment are not supported by these data.

Pro- and antiinflammatory cytokine production after radiofrequency ablation of unresectable hepatic tumors.

BACKGROUND: Experience using radiofrequency ablation (RFA) for treating unresectable hepatic malignancies is expanding, with promising outcomes and fewer complications compared with cryotherapy. STUDY DESIGN: This study examined systemic inflammatory responses after RFA as measured by the appearance of postoperative symptoms and cytokine production. Seventeen patients (11 men, 6 women) aged 40 to 85 years (mean 64.2 years) with unresectable primary and metastatic hepatic tumors underwent RFA. Mean liver volume treated with RFA was 35.3% +/- 3.6% (SEM) (median 36.8%). Plasma cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-1ra, IL-6, IL-8, IL-10, p55, and p75) were measured from anesthesia induction through 48 hours after RFA. Ex vivo whole-blood cytokine production was measured at baseline, 24 hours, and 48 hours after RFA. RESULTS: Cytokine and cytokine-receptor production were not notably altered by RFA. Ex vivo whole-blood endotoxin stimulation indicated that intrinsic cellular immune function remained intact after treatment, although modest decreases in stimulated tumor necrosis factor alpha production were observed 24 to 48 hours after RFA. Variceal bleeding, hepatic failure, and death occurred in one patient 30 days after RFA. None of the remaining patients exhibited tachycardia or hypotension. Fevers (> or = 38.5 degrees C) developed in three patients during the first 48 hours postoperatively. There was no association between plasma cytokines and postoperative complications. CONCLUSIONS: In contrast to previous reports using cryotherapy, systemic inflammatory responses as measured by increased cytokines were not observed after RFA. The cryotherapy-induced "cryoshock" phenomenon was not observed in patients undergoing RFA in our study. We conclude that RFA ablation is fundamentally different than cryotherapy and apparently does not stimulate Kupffer and other hepatic macrophages to produce proinflammatory cytokines.

Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy.

BACKGROUND: Our institution has previously demonstrated a survival advantage conferred by preoperative neoadjuvant therapy for locally advanced rectal cancers. We now report our results using transanal excision as definitive surgical therapy in a selected group of patients who experienced significant downstaging of T3 rectal cancers after neoadjuvant therapy. STUDY DESIGN: Seventy-four patients diagnosed with locally advanced (T3) rectal cancers were treated with neoadjuvant chemoradiotherapy. After neoadjuvant therapy, 11 (14.9%) patients who had significant downstaging of their tumors were selected to undergo transanal excision of their residual rectal cancers. Intraoperative cryostat evaluation was used to confirm negative margin status, and all patients were subsequently followed with routine endoscopy, transrectal ultrasonography, and digital rectal examinations. RESULTS: Tumors were located between 1 cm and 7 cm from the anal verge (mean 4.3 +/- 0.6 cm), and were located in lateral, anterior, and posterior positions. Mean followup was 55.2 +/- 8.9 months (median 47.9 months). Imaging studies using CT, MRI, transrectal ultrasonography, or combination demonstrated suspicious lymph nodes in three patients. After neoadjuvant therapy, these lymph nodes were no longer demonstrated in two patients. There were no local recurrences, nodal metastases, or operative mortalities. One patient (9%) developed distant metastases (pulmonary nodules), and remains alive 30 months after transanal excision. One patient (9%) experienced sphincter laxity, which was successfully repaired, and is now asymptomatic. One patient (9%) developed postoperative urgency that resolved spontaneously. CONCLUSIONS: In patients who have initial bulky (T3) lesions, and experience significant downstaging after neoadjuvant chemoradiotherapy, transanal excision appears to be a safe and effective treatment, preserving sphincter function and avoiding laparotomy.

Hepatic artery embolization for control of symptoms, octreotide requirements, and tumor progression in metastatic carcinoid tumors.

Hepatic artery embolization (HAE) has been utilized for treatment of advanced hepatic carcinoid metastases, with promising symptom palliation and tumor control. Our institution employs transcatheter HAE using Lipiodol/Gelfoam for treatment of carcinoid hepatic metastases, and this report presents our experience with twenty-four patients, examining symptom control, quality-of-life, octreotide dependence, and tumor progression. Twenty-four (11 male, 13 female, mean age = 59.4 +/- 2.5 yr) patients with carcinoid and unresectable hepatic metastases, confirmed by urinary 5-hydroxyindole acetic acid (5-HIAA) measurement and biopsy, were treated with Lipiodol/Gelfoam HAE from 1993-2001. Median follow-up was 35.0 months. Before HAE, 14 patients (58.3%) had malignant carcinoid syndrome, with symptoms quantified using our previously reported Carcinoid Symptom Severity Score, and 13 patients (54.2%) required octreotide for symptom palliation. Following treatment, symptom severity, octreotide dose, and tumor response were measured. Asymptomatic patients did not develop symptoms or require following treatment. Hepatic metastases remained stable (n = 4) or decreased (n = 19) in 23 patients (95.8%). Mean pretreatment Symptom Severity Scores (3.8 +/- 0.2), decreased to 1.4 +/- 0.1 post-treatment (P < 0.00001), with 64.3% of patients becoming asymptomatic. Mean pretreatment octreotide dosages (679.6 +/- 73.0 microg/d), decreased to 262.9 +/- 92.7 microg/d (P = 0.0024) post-treatment, with 46.2% of patients discontinuing octreotide. There were no treatment-related serious complications or deaths. This study demonstrates that Lipiodol/Gelfoam HAE produces excellent control of malignant carcinoid syndrome, allowing patients to decrease or eliminate use of octreotide, while controlling hepatic tumor burden.

An Internet-based tool for evaluating third-year medical student performance.

BACKGROUND: Shortened non-primary care medical school clerkships have increased time pressures for accurate assessment of student knowledge, skills, and attitudes. Paper-based student evaluations suffer from low response rates, inefficient data acquisition and analysis, and difficulty obtaining input from multiple evaluators. This project describes the development of a Web-based model for evaluating third-year medical student performance, improving evaluation response rates, and including multiple evaluators' input. METHODS: A secure Web-based system was designed to maintain evaluation data (11-item competency-based evaluations, oral examinations, National Board of Medical Examiners surgery test, and objective structured clinical examination) for the third-year surgery clerkship. Historical response rate, completion time, and administrative effort data were compared with data obtained using the Web-based model. RESULTS: Faculty response rates improved from 71.3% to 89.9%, with response times decreased from 28.0 +/- 3.0 to 9.0 +/- 0.7 days using the Web-based model. Administrative time requirements decreased from 5 days to 2 hours per rotation, and manual data entry, analysis, and reporting were eliminated through e-mail evaluator notification, direct data entry, and real-time analysis. Evaluator satisfaction was subjectively higher using the Web-based model. CONCLUSIONS: The Web-based 360-degree evaluation model improves third-year medical student assessment by including residents, reducing time and cost, and by providing a faster, more inclusive, and efficient evaluation.

Sequential dermal-peritumoral radiocolloid injection for sentinel node biopsy for breast cancer: the University of Florida experience.

Although sentinel lymph node (SLN) biopsy is rapidly becoming the standard of care for small breast cancers the optimal radiocolloid injection technique remains controversial. We report our experience with sequential dermal-peritumoral radiocolloid injection that takes advantage of both techniques. One hundred eighteen patients with clinical stage T(is), T1, T2 and N0 breast cancer underwent SLN biopsy at the University of Florida. Twelve to 18 hours before surgery patients received either an injection of 0.5 to 1.0 mCi 50:50 filtered:unfiltered technetium sulfur colloid into the dermis overlying the tumor and/or a peritumoral injection of a 3 to 4-mCi of radiocolloid 30 minutes later. Dynamic lymphoscintigraphy was performed and the topographical location of all imaged lymph nodes was marked on the skin. The next morning the surgeon utilized a hand-held gamma probe to remove all SLN(s) defined as any lymph node with radioactive counts 10 per cent or more of the ex vivo counts of the most radioactive SLN [internal mammary (IM) nodes were not removed]. The SLN identification rate was 98.5 per cent (3 IM nodes) for dermal injection (d.), 83.3 per cent (1 IM node) for peritumoral injection (p.), and 100 per cent (14 IM nodes) for sequential dermal-peritumoral injection (d.p.) (p < 0.05 DP versus D). Sequential d.p. 50:50 filtered:unfiltered technetium sulfur colloid injection results in a rapid, high SLN identification rate that persists until surgery the next morning. Delineation of nonaxillary SLNs may lead to more accurate breast cancer staging and may also influence the delivery of IM node radiation.

Evaluation of face-mounted binocular video display for laparoscopy: outcomes of psychometric skills testing and surgeon satisfaction.

OBJECTIVES: Improved digital video cameras and high-resolution video displays have greatly enhanced laparoscopic surgery. However, the size and distance of the video display and the location of the monitor continue to be impediments in laparoscopy, providing unsatisfactory operative visualization and causing the development of neck and back strain in surgeons performing long procedures. The purpose of this study was to evaluate the use of a face-mounted binocular high-resolution video display by means of standardized measurements of laparoscopic skill, and to compare procedure speed and surgeon satisfaction with the binocular display, open operative visualization, and standard laparoscopic monitor views. METHODS: The surgical faculty and resident trainees (n = 22) underwent two standardized laparoscopic psychometric skills tests of fine motor control and bimanual operative facility. Testing was performed first with the use of laparoscopic instruments in direct view of the participants; sufficient repetitions were allowed so that plateau levels were obtained in task speed. Video camera-based imaging displayed on the face-mounted binocular video display and a standard video monitor were then used to repeat identical tests. Test times were compared between the open view, face-mounted display (FMD) view, and standard laparoscopic monitor view groups. A Likert-scale based assessment was conducted to examine operator impressions of neck and back strain, visual acuity, and overall satisfaction. RESULTS: Performance with the standard laparoscopic monitor was significantly slower than with the direct view on both fine motor (mean, 85.0 +/- 7.1 s vs. 56.4 +/- 5.7 s; P <.0001) and bimanual (mean, 80.8 +/- 7.0 s vs. 40.2 +/- 2.6 s; P =.009) psychometric skills tests. The FMD view performance was significantly faster than the standard laparoscopic monitor performance for both the bimanual (mean, 72.2 +/- 7.6 s vs. 85.0 +/- 7.2 s; P =.001) and fine motor (mean, 59.3 +/- 4.7 s vs. 80.8 +/- 7.0 s; P =.004) tests. The scores on a Likert Scale satisfaction survey of the use of the FMD unit for neck and back strain (mean, 4.27 +/- 0.20), visual acuity (mean, 3.93 +/- 0.10), and overall satisfaction (mean, 4.16 +/- 0.20) were high (scale: 1, worst; 5, ideal). CONCLUSIONS: A face-mounted high-resolution video display unit reduces neck and back strain and improves both visualization and overall satisfaction in comparison with standard laparoscopic display monitors; surgical performance is better than with standard laparoscopic imaging as assessed by standardized psychometric skills testing.

Web-based minimally invasive surgery training: competency assessment in PGY 1-2 surgical residents.

OBJECTIVES: Little published literature describes accurate evaluation and assessment of surgical residents' technical competencies. Work-hour limitations and the proposed changes in training duration challenge our ability to provide core technical competencies, particularly during PGY-1-2. We identified minimally invasive surgery as a particularly challenging competency training area, requiring significant allocation of resident and faculty time and resources, with inconsistent training results. This project evaluated a standardized competency training curriculum in minimally invasive surgery in comparison to existing training. METHODS: The Laparoscopy 101-a Resource for Resident Education minimally invasive surgery competency training curriculum consists of CD-ROM-based self-paced didactic self-instruction modules, skills laboratories, and web-based testing, evaluation, and reporting. Five didactic self-study modules and their corresponding web-based examinations were selected for this study. PGY 1-2 residents (11/group) were enrolled. PGY-1 residents received no formal minimally invasive surgery training in our program before participating, whereas PGY-2 residents were exposed to the minimally invasive surgery training program in place in our department. PGY-1 residents completed the training modules and web-based testing over 4 days. PGY-2 residents underwent testing before (pre-test) and after (post-test) completing identical training modules and testing over an identical time period. Test results were examined and compared in both groups. A user-satisfaction survey assessed resident opinions about the quality of the curriculum, use of the CD-ROM/web-based system, and trainee perceptions about performance. RESULTS: PGY-2 Pre-test scores were equivalent to PGY-1 scores after training (mean overall performance, 52.4% vs 65.5% p = ns). PGY-2 Post-test scores were significantly higher when compared with pre-test scores (mean overall performance; pre: 52.4% vs post: 85.3% p <== 0.001). Interestingly, post-training scores were significantly higher for PGY-2 than PGY-1 (mean overall performance PGY-1: 52.4% vs PGY-2: 65.5% p = ns). Competencies achieved persisted 6 months after initial training in both PGY 1-2 groups without additional training using this curriculum. Overall user satisfaction was positive in each category evaluated. CONCLUSIONS: The Laparoscopy 101 minimally invasive surgery curriculum (1) p;rovides a structured self-paced curriculum for minimally invasive didactic training that is well accepted by trainees; (2) yields PGY-1 competencies equivalent to PGY-2 who receive training in our department's existing program; and (3) yields significant improvement in PGY-2 minimally invasive surgery competencies. Training effects persist to 6 months without reinforcement. Our observations of PGY-2 performance and competency suggest that this training would best be instituted during PGY-2.

Patient outcomes after axillary lymph node dissection for breast cancer: use of postoperative continuous local anesthesia infusion.

BACKGROUND: Although considered a safe surgical procedure, axillary lymph node dissection (ALND) is associated with postoperative numbness, paresthesias, pain, and muscle weakness. Despite meticulous surgical technique and the absence of long thoracic or thoracodorsal nerve injury, the risk of these complications are reported as great as 35% to 50%, with a subset of patients developing chronic pain syndromes. METHODS: Female patients (n = 27) undergoing Level I-II ALND for breast cancer were recruited. After ALND, patients were randomized to three groups. Group 1 received standard axillary lymph node dissection. Patients assigned to group 2 or 3 (double-blinded) received 120 h continuous 0.9% saline solution or 0.5% bupivacaine using a catheter placed into the axilla and delivered by an elastomeric pump device. After routine postoperative care, patients were discharged with oral opioid analgesics. Twice-daily assessment of pain, sedation, and nausea were conducted using validated visual-analog scale measures. Daily and total opioid analgesic requirements after surgery were recorded. RESULTS: Patients treated with a continuous infusion of bupivacaine experienced significantly lower pain scores (P < 0.001) during the first 5 postoperative days. Postoperative opioid analgesic requirements also were significantly decreased in the bupivacaine group, and these effects persisted until postoperative day 14 (P < 0.001). Concomitant to the observed decreases in pain and oral opioid requirements, nausea and morning sedation also were significantly reduced. There were no pump-related complications, wound infections, or postoperative axillary fluid collections. CONCLUSIONS: The use of continuous administration of bupivicaine after ALND significantly decreases pain and opioid analgesic requirements, with concomitant decreases in nausea and sedation. This study provides encouraging evidence of the therapeutic benefits of continuous infusion of local anesthesia and may represent a valuable adjunct for surgical patients who require ALND, including those with breast cancer and melanoma.

Integrating information technologies as tools for surgical research.

BACKGROUND: Surgical research is dependent upon information technologies. Selection of the computer, operating system, and software tool that best support the surgical investigator's needs requires careful planning before research commences. MATERIALS AND METHODS: This manuscript presents a brief tutorial on how surgical investigators can best select these information technologies, with comparisons and recommendations between existing systems, software, and solutions. RESULTS: Privacy concerns, based upon HIPAA and other regulations, now require careful proactive attention to avoid legal penalties, civil litigation, and financial loss. Security issues are included as part of the discussions related to selection and application of information technology. CONCLUSIONS: This material was derived from a segment of the Association for Academic Surgery's Fundamentals of Surgical Research course.

Duodenal perforation with an inferior vena cava filter: an unusual cause of abdominal pain.

The insertion of inferior vena cava (IVC) filters results in device migration at rates that exceed 50% in some studies, although the clinical significance of migration remains in question. These filters can also erode or penetrate the IVC wall, injuring adjacent retroperitoneal and abdominal structures. The risk of erosion or perforation is estimated to be as much as 25%, although clinical symptoms are observed far less frequently in patients with these complications. We describe the presentation, evaluation, and treatment of a patient with an IVC strut protruding into the duodenum. This case report discusses complications, presenting symptoms, and treatment of patients with IVC filters complications.

Role of radiation therapy in the treatment of resectable rectal adenocarcinoma.

The purpose of this study is to review the role of radiation therapy in the treatment of resectable rectal adenocarcinoma. Selection criteria, treatment techniques, and results are discussed.