Search

For several decades, cholesterol has been thought to cause ASCVD. Limiting dietary cholesterol intake has been recommended to reduce the risk of the disease. However, several recent epidemiological studies do not support a relationship between dietary cholesterol and/or blood cholesterol and ASCVD. Consequently, the role of cholesterol in atherogenesis is now uncertain. Much evidence indicates that TGF-β, an anti-inflammatory cytokine, protects against ASCVD and that suppression of canonical TGF-β signaling (Smad2-dependent) is involved in atherogenesis. We had hypothesized that cholesterol causes ASCVD by suppressing canonical TGF-β signaling in vascular endothelium. To test this hypothesis, we determine the effects of cholesterol, 7-dehydrocholesterol (7-DHC; the biosynthetic precursor of cholesterol), and other sterols on canonical TGF-β signaling. We use Mv1Lu cells (a model cell system for studying TGF-β activity) stably expressing the Smad2-dependent luciferase reporter gene. We demonstrate that 7-DHC (but not cholesterol or other sterols) effectively suppresses the TGF-β-stimulated luciferase activity. We also demonstrate that 7-DHC suppresses TGF-β-stimulated luciferase activity by promoting lipid raft/caveolae formation and subsequently recruiting cell-surface TGF-β receptors from non-lipid raft microdomains to lipid rafts/caveolae where TGF-β receptors become inactive in transducing canonical signaling and undergo rapid degradation upon TGF-β binding. We determine this by cell-surface 125 I-TGF-β-cross-linking and sucrose density gradient ultracentrifugation. We further demonstrate that methyl-β-cyclodextrin (MβCD), a sterol-chelating agent, reverses 7-DHC-induced suppression of TGF-β-stimulated luciferase activity by extrusion of 7-DHC from resident lipid rafts/caveolae. These results suggest that 7-DHC, but not cholesterol, promotes lipid raft/caveolae formation, leading to suppression of canonical TGF-β signaling and atherogenesis. J. Cell. Biochem. 118: 1387-1400, 2017. © 2016 Wiley Periodicals, Inc.

Background Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty. Patients and methods Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL. Results From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51–86] in the minimal surveillance group and 62 months (IQR 50–85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention-to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens. Conclusion Our findings support the conclusions of other randomized clinical trials, which show that early diagnosis of cancer recurrence is not associated with OS benefit. ClinicalTrials.gov NCT02409472.

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Agricultural soils are responsible for a majority of human caused greenhouse gas (GHG) production, such as N₂O and carbon dioxide (CO₂). Nitrous oxide is a potent GHG that stays in the atmosphere for at least 100 years. It is also an ozone-depleting gas. Carbon dioxide is problematic due to its abundance in the atmosphere. These GHGs, along with methane, have had a significant impact on climate change. Claypan soils are characterized as having a significantly higher clay content deeper in the soil profile compared to the layers directly above it. The goal of this research was to investigate the impact N fertilizer placement has on GHG emissions and corn growth. The specific research objectives were to determine the effects of urea fertilizer placement with and without a nitrification inhibitor (NI) on cumulative soil GHG emissions (N₂O and CO₂) and to assess the effects of urea fertilizer placement with and without a NI on plant N uptake, N use efficiency (NUE), and corn (Zea mays L.) production, on a poorly drained claypan soil in Northeastern Missouri. A NI helps reduce the amount of nitrous oxide produced. Field studies were conducted in 2014 and 2015. Soil greenhouse gas emissions were measured frequently throughout the growing season to determine flux and cumulative N₂O and CO₂ emissions. Soil water content and soil temperature were also assessed at each gas sampling event. Rainfall was higher than the 10-year average over the growing season for both 2014 and 2015 and possibly resulted in increased environmental N loss. Soil N₂O and CO₂ emissions were higher during the 2015 growing season. The UDB treatment produced the greatest amount of cumulative soil N₂O emissions during both growth seasons at 100 and 354 g N₂O-N ha⁻¹. Deep banded urea without a NI resulted in the highest soil CO₂ production in 2014 and UAA had the greatest cumulative CO₂ emissions in 2015 at approximately 11 and 17 kg CO₂-C ha⁻¹, respectively. Incorporating urea to a depth of 8 cm, deep banding urea, and deep banding urea with a NI all resulted in significantly higher yields of corn by as much as much as 10%. Deep banding urea with a NI provided as high as a 48% increase in grain yield compared to other treatments in 2015. The highest yields occurred in 2014 when there were lower N₂O emissions. In 2015, there were higher N₂O emissions and lower yields. This research suggests that urea fertilizer placement has an impact on GHG emissions and corn growth and this information should be provided to farmers who are interested in producing more corn and losing less N. The amount of rainfall during the growing season may also influence soil GHG emissions and corn growth. More research should be conducted to understand to what extent climatic variability impacts GHG and crop production.

Highlights • In a prior case series, we noted a sign on CT associated with inguinoscrotal herniation of the ureter. • In this study, we analyzed all CT urograms performed at our institution over 1 year. • Deviation of the ureter from the psoas muscle at L4 by >1 cm should raise suspicion for a distal ureteral anomaly. • Morbid obesity and congenital anomalies may result in a similar imaging appearance. • Awareness of this anomaly can have significant operative implications., Introduction An aberrant course of the distal ureter can pose a risk of ureteral injury during surgery for inguinal hernia repair and other groin operations. In a recent case series of inguinoscrotal hernation of the ureter, we found that each affected ureter was markedly anterior to the psoas muscle at its mid-point on abdominal CT. We hypothesized that this abnormality in the abdominal course of the ureter would predict the potentially hazardous aberrant course of the distal ureter. Presentation of cases We reviewed all evaluable CT urograms performed at St. Louis University Hospital from June 2012 to July 2013 and measured the ureteral course at several anatomically fixed points. Discussion 93% (50/54) of ureters deviated by less than 1 cm from the psoas muscle in their mid-course (at the level of the L4 vertebra). Reasons for anterior deviation of the ureter in this study included morbid obesity with prominent retroperitoneal fat, congenital renal abnormality, and post-traumatic renal/retroperitoneal hematoma. We determined that the optimal level on abdominal CT to detect the displaced ureter was the mid-body of the L4 vertebra. Conclusion Anterior deviation of the ureter in its mid-course appears to predict inguinoscrotal herniation of the ureter. This finding is a sensitive predictor and should raise concern for this anomaly in the appropriate clinical setting. It is not entirely specific as morbid obesity and congenital anomalies may result in a similar imaging appearance. We believe that this association has not been reported previously. Awareness of this anomaly can have significant operative implications.

Regular consumption of moderate amounts of ethanol has important health benefits on atherosclerotic cardiovascular disease (ASCVD). Overindulgence can cause many diseases, particularly alcoholic liver disease (ALD). The mechanisms by which ethanol causes both beneficial and harmful effects on human health are poorly understood. Here we demonstrate that ethanol enhances TGF-β-stimulated luciferase activity with a maximum of 0.5-1% (v/v) in Mv1Lu cells stably expressing a luciferase reporter gene containing Smad2-dependent elements. In Mv1Lu cells, 0.5% ethanol increases the level of P-Smad2, a canonical TGF-β signaling sensor, by ∼ 2-3-fold. Ethanol (0.5%) increases cell-surface expression of the type II TGF-β receptor (TβR-II) by ∼ 2-3-fold from its intracellular pool, as determined by I(125) -TGF-β-cross-linking/Western blot analysis. Sucrose density gradient ultracentrifugation and indirect immunofluorescence staining analyses reveal that ethanol (0.5% and 1%) also displaces cell-surface TβR-I and TβR-II from lipid rafts/caveolae and facilitates translocation of these receptors to non-lipid raft microdomains where canonical signaling occurs. These results suggest that ethanol enhances canonical TGF-β signaling by increasing non-lipid raft microdomain localization of the TGF-β receptors. Since TGF-β plays a protective role in ASCVD but can also cause ALD, the TGF-β enhancer activity of ethanol at low and high doses appears to be responsible for both beneficial and harmful effects. Ethanol also disrupts the location of lipid raft/caveolae of other membrane proteins (e.g., neurotransmitter, growth factor/cytokine, and G protein-coupled receptors) which utilize lipid rafts/caveolae as signaling platforms. Displacement of these membrane proteins induced by ethanol may result in a variety of pathologies in nerve, heart and other tissues.

Barring unusual circumstances, sigmoid colostomy is the optimal technique for management of defecation in spinal cord injury (SCI) patients. We sought to provide evidence that a sigmoid colostomy is not difficult to perform in SCI patients and has better long-term results. The St. Louis Department of Veterans Affairs has a Commission on Accreditation of Rehabilitation Facilities (CARF)–approved SCI Unit. We reviewed the operative notes on all SCI patients who received a colostomy for fecal management by three ASCRS-certified colorectal surgeons at the St. Louis Department of Veterans Affairs from January 1,2007 to November 26, 2012. There were 27 operations for which the recorded indication for surgery suggested that the primary disorder was SCI. Fourteen had traumatic SCI of the thoracic and/or lumbar spine and were evaluable. Of these 14 patients, 12 had laparoscopic sigmoid colostomy and two had open sigmoid colostomy. We encountered one evaluable patient with a remarkably large amount of retroperitoneal bony debris who successfully underwent laparoscopic sigmoid colostomy. In conclusion, sigmoid colostomy is the consensus optimal procedure for fecal management in SCI patients. Laparoscopic procedures are preferred. Care providers should specify sigmoid colostomy when contacting a surgeon.

Aims: In the vast majority of instances, closure of abdominal wall defects relies on the tensile strength of transposed native tissue and/or prosthetic material. The purpose of this report is to alert clinicians to a different strategy for closure that we have used successfully on several occasions. Presentation of Case: A 72 year old man had a bulky inguinal nodal metastasis from cutaneous squamous cell carcinoma. He had an extended radical groin dissection including full thickness abdominal wall resection, with primary closure, followed by external beam radiotherapy. After 30 months, he developed an abdominal wall hernia and enterocutaneous fistula at the surgical site. Direct closure and local vascularized flaps were not feasible. Obturation of the defect by omentum was employed, taking advantage of its relative incompressibility rather than its minimal tensile strength. The wound was subsequently covered by a skin graft. The patient survived 10 years with an intact hernia repair and died of unrelated causes. Discussion: The technique has yielded good results. Case Study Johnson et al.; BJMMR, 7(12): 1039-1043, 2015; Article no.BJMMR.2015.42

Objective: We aimed to determine whether the variability in surveillance strategies after curativeintent primary treatment of ovarian cancer is related to practitioner age. Materials and Methods: The 943 members of The Society of Gynecologic Oncology (SGO) were surveyed by conventional mail to quantify their surveillance strategies for patients with ovarian carcinoma after potentially curative initial treatment. We requested data regarding the recommended frequency of 10 commonly employed surveillance modalities. Age was used as a proxy for time since formal residency training. Results: There were 283 responders: 58 were aged 30-39, 114 were aged 40-49, 70 were aged 50-59, and 41 were aged ≥ 60. Older gynecologic oncologists (60+) ordered office visits and pelvic examinations more frequently than younger gynecologic oncologists in year 1 (p

a b s t r a c t INTRODUCTION: Descent of the ureter into the inguinal canal or scrotum is rare but undoubtedly under- reported. Most known cases were recognized at the time of surgery for hernia repair. We encountered five cases recently. PRESENTATION OF CASE: We reviewed the records and CT images of five patients with inguinal hernias containing a segment of the ureter. All of our cases, like most reported cases, featured obese adult males. Our cases had different outcomes, ranging from inadvertent injury of the displaced ureter to correction of the anomaly at the time of hernia repair. DISCUSSION: In all of our cases, the affected ureter was displaced anteriorly from the psoas muscle by greater than 1 cm at the level of the L4 vertebra on abdominal CT. This association has not been previously described. CONCLUSION: Pre-operative diagnosis by CT can prevent injury to the ureter. We hypothesize that anterior displacement of the ureter at the level of L4 as seen on CT may be predictive of inguinoscrotal herniation of the ureter. © 2015 The Authors. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

CRSBP-1 (mammalian LYVE-1) is a membrane glycoprotein highly expressed in lymphatic endothelial cells (LECs). It has multiple ligands, including hyaluronic acid (HA) and growth factors/cytokines (e.g., PDGF-BB and VEGF-A) containing CRS motifs (clusters of basic amino-acid residues). The ligand binding activities are mediated by Link module and acidic-amino-acid-rich (AAAR) domains, respectively. These CRSBP-1/LYVE-1 ligands have been shown to induce opening of lymphatic intercellular junctions in LEC monolayers and in lymphatic vessels in wild-type mice. We hypothesize that CRSBP-1/LYVE-1 ligands, particularly CRS-containing growth factors/cytokines, are secreted by immune and cancer cells for lymphatic entry during adaptive immune responses and lymphatic metastasis. We have looked into the origin of the Link module and AAAR domain of LYVE-1 in evolution and its association with the development of lymph nodes and efficient adaptive immunity. Lymph nodes represent the only major recent innovation of the adaptive immune systems in evolution particularly to mammals and bird. Here we demonstrate that the development of the LYVE-1 gene with the AAAR domain in evolution is associated with acquisition of lymph nodes and adaptive immunity. LYVE-1 from other species, which have no lymph nodes, lack the AAAR domain and efficient adaptive immunity. Synthetic CRSBP-1 ligands PDGF and VEGF peptides, which contain the CRS motifs of PDGF-BB and VEGF-A, respectively, specifically bind to CRSBP-1 but do not interact with either PDGFβR or VEGFR2. These peptides function as adjuvants by enhancing adaptive immunity of pseudorabies virus (PRV) vaccine in pigs. These results support the notion that LYVE-1 is involved in adaptive immunity in mammals.

The incidence of breast cancer has been on the rise in the United States over the past several decades. The advanced longevity of the population during this same time period, specifically of elderly women, translates to increases in the absolute number of women diagnosed with breast cancer yearly. This, in combination with decreasing mortality rates, has now led to an increase in the number of breast cancer survivors who need long-term follow-up. There has been significant debate over what tests should be obtained, how often they should be obtained, how long surveillance should be continued, and by whom this should be performed. We review the published guidelines for surveillance, available data regarding low- versus high-intensity surveillance plans, current practice patterns, and recommendations for future strategies.

BACKGROUND: American Society of Clinical Oncology (ASCO) guidelines recommend only office visits and mammograms as the primary modalities for patient surveillance after treatment for breast carcinoma. This study aimed to quantify differences in posttreatment surveillance among medical oncologists, radiation oncologists, and surgeons. METHODS: We e-mailed a survey to the 3,245 ASCO members who identified themselves as having breast cancer as a major focus of their practices. Questions assessed the frequency of use of 12 specific surveillance modalities for 5 posttreatment years. RESULTS: Of 1,012 total responses, 846 were evaluable: 5% from radiation oncologists, 70% from medical oncologists, and 10% from surgeons; 15% were unspecified. Marked variation in surveillance practices were noted within each specialty and among specialties. CONCLUSION: There are notable variations in surveillance intensity. This suggests overuse or underuse or misuse of scarce medical resources. Published by Elsevier Inc.

In May of 2011, a live mass stranding of 26 short-finned pilot whales (Globicephala macrorhynchus) occurred in the lower Florida Keys. Five surviving whales were transferred from the original stranding site to a nearby marine mammal rehabilitation facility where they were constantly attended to by a team of volunteers. Bacteria cultured during the routine clinical care of the whales and necropsy of a deceased whale included methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). In order to investigate potential sources or reservoirs of MSSA and MRSA, samples were obtained from human volunteers, whales, seawater, and sand from multiple sites at the facility, nearby recreational beaches, and a canal. Samples were collected on 3 days. The second collection day was 2 weeks after the first, and the third collection day was 2 months after the last animal was removed from the facility. MRSA and MSSA were isolated on each day from the facility when animals and volunteers were present. MSSA was found at an adjacent beach on all three collection days. Isolates were characterized by utilizing a combination of quantitative real-time PCR to determine the presence of mecA and genes associated with virulence, staphylococcal protein A typing, staphylococcal cassette chromosome mec typing, multilocus sequence typing, and pulsed field gel electrophoresis (PFGE). Using these methods, clonally related MRSA were isolated from multiple environmental locations as well as from humans and animals. Non-identical but genetically similar MSSA and MRSA were also identified from distinct sources within this sample pool. PFGE indicated that the majority of MRSA isolates were clonally related to the prototype human strain USA300. These studies support the notion that S. aureus may be shed into an environment by humans or pilot whales and subsequently colonize or infect exposed new hosts.

Barring unusual circumstances, sigmoid colostomy is the optimal technique for management of defecation in spinal cord injury (SCI) patients. We sought to provide evidence that a sigmoid colostomy is not difficult to perform in SCI patients and has better long-term results. The St. Louis Department of Veterans Affairs has a Commission on Accreditation of Rehabilitation Facilities (CARF)-approved SCI Unit. We reviewed the operative notes on all SCI patients who received a colostomy for fecal management by three ASCRS-certified colorectal surgeons at the St. Louis Department of Veterans Affairs from January 1, 2007 to November 26, 2012. There were 27 operations for which the recorded indication for surgery suggested that the primary disorder was SCI. Fourteen had traumatic SCI of the thoracic and/or lumbar spine and were evaluable. Of these 14 patients, 12 had laparoscopic sigmoid colostomy and two had open sigmoid colostomy. We encountered one evaluable patient with a remarkably large amount of retroperitoneal bony debris who successfully underwent laparoscopic sigmoid colostomy. In conclusion, sigmoid colostomy is the consensus optimal procedure for fecal management in SCI patients. Laparoscopic procedures are preferred. Care providers should specify sigmoid colostomy when contacting a surgeon.

Breast cancer is a major health problem worldwide. The median survival duration for patients with metastatic breast cancer is two to three years. Approximately 1% of populations worldwide have schizophrenia. The manner in which schizophrenic patients fare when diagnosed with metastatic breast carcinoma (MBC) was evaluated. We queried the National Department of Veterans Affairs (DVA) datasets using computer codes for a pre-existing diagnosis of schizophrenia and a later diagnosis of breast carcinoma. Chart-based data concerning the identified subjects were then requested. Previously determined inclusion and exclusion criteria were applied to select evaluable patients from the medical records, prior to extracting demographic details and data concerning the treatment course in each subject. Ten patients had distant metastases at initial diagnosis, while seven developed MBC following prior curative-intent treatment. Two patients refused therapy. Ten did not comply with recommended management. Five harmed or threatened physicians, other caregivers or themselves. Schizophrenic patients with MBC often fail to understand the nature of their illnesses. Often they do not accept palliative treatment, while a number of them do not comply with therapy, once initiated. They often exhibit behaviors that are detrimental to themselves or others. Formal psychiatric consultation is therefore necessary in patients. Several detrimental behaviors may be predicted reliably by history alone.

To determine how physicians monitor their patients after initial curative-intent treatment for breast carcinoma.A custom-designed survey instrument with four idealized patient vignettes (TNM stages 0 to III) was e-mailed to the 3,245 members of ASCO who had identified themselves as having breast cancer as a major focus of their practice. Respondents were asked how they use 12 specific follow-up modalities during post-treatment years 1 to 5 for each vignette. Mean, median, standard deviation, and range of the intensity of use for each modality were calculated for the four vignettes.Of the 3,245 ASCO members surveyed, 1,012 (31%) responded. Of these, 915 (90%) were evaluable and were included in our analysis. Office visit, mammogram, complete blood count, and liver function tests were the most commonly recommended surveillance modalities. There was marked variation in surveillance intensity. For example, office visit was recommended 4.1 ± 2.2 times (mean ± SD) in year 1 after curative treatment of a patient with stage III breast cancer. Similar variation was observed for all modalities.The intensity of post-treatment surveillance performed by ASCO members caring for patients with breast cancer varies markedly despite evidence from well-designed, adequately powered randomized controlled trials. Many modalities not recommended by ASCO guidelines are used routinely, which constitutes evidence of overuse. The lack of consensus is likely due to multiple factors and constitutes an appealing target for interventions to rationalize surveillance.

Objective Patient surveillance after potentially curative treatment of ovarian carcinoma has important clinical and financial implications for patients and society. The optimal intensity of surveillance for these patients is unknown. We aimed to document the current follow-up practice patterns of gynecologic oncologists. Methods We created four idealized vignettes describing patients with stages I–III ovarian cancer. We mailed a custom-designed survey instrument based on the vignettes to the members of the Society of Gynecologic Oncologists (SGO). SGO members were asked, via this instrument, how often they requested 11 discrete follow-up evaluations for their patients for the first 10 postoperative years after treatment with curative intent. Results We received 283 evaluable responses (30%) from the 943 SGO members and candidate members. The most frequently performed items for each year were office visit, pelvic examination, and serum CA-125 level. Imaging studies such as chest X-ray, abdominal–pelvic CT, chest CT, abdominal–pelvic MRI, and transvaginal ultrasound were rarely recommended. There was marked variation in the frequency of use of most tests. There was a decrease in the frequency of testing over time for all modalities. Conclusion This dataset provides detailed documentation of the self-reported surveillance practices of highly credentialed experts who manage patients with ovarian cancer in the 21st century. The optimal follow-up strategy remains unknown and controversial. Our survey showed marked variation in surveillance intensity. Identifying the sources of this variation warrants further research.

Background. Surveillance strategies for of rectal cancer patients after potentially curative treatment vary significantly. We investigated whether the age of the surgeon affects choice of surveillance strategy. Methods. We developed vignetres depicting 4 generally healthy patients with rectal cancer of various stages who received various treatments. A questionnaire based on these vignettes was sent to the 1795 members of the American Society of Colon and Rectal Surgeons (ASCRS). Results. There was no significant relationship between surgeon age and follow-up test-ordering schedules for any of the 4 vignettes. There was no significant relationship between surgeon age and 10 of the 11 possible motivating factors. Conclusions. Follow-up testing among ASCRS surgeons does not vary significantly among surgeons trained at various times. The motivation for follow-up testing is nearly uniform among age strate.

CRSBP-1, a membrane glycoprotein, can mediate cell-surface retention of secreted growth factors containing CRS motifs such as PDGF-BB. CRSBP-1 has recently been found to be identical to LYVE-1, a specific marker for lymphatic capillary endothelial cells. The in vivo role of CRSBP-1/LYVE-1 is unknown. CRSBP-1-null mice are overtly normal and fertile but exhibit identifiable morphological and functional alterations of lymphatic capillary vessels in certain tissues, marked by the constitutively increased interstitial-lymphatic flow and lack of typical irregularly-shaped lumens. The CRSBP-1 ligands PDGF-BB and HA enhance interstitial-lymphatic flow in wild-type mice but not in CRSBP-1-null animals.

Background Colon cancer is relatively common; however, the results of treatment have marginally improved over the last half century. Though about 85% of patients have colorectal tumors resected with curative intent, a significant number of these patients will eventually die from cancer. As a result, many clinicians have advocated intensive follow-up in such patients as an attempt to increase survival. Data Sources A review of the literature focusing on studies that have specifically addressed postoperative surveillance programs in patients with colorectal cancer was conducted. Only studies with level A evidence were included. Further references were obtained through cross-referencing the bibliography cited in each work. Conclusion One of the six prospective randomized studies demonstrated a statistically significant survival benefit. Undoubtedly, survival benefits can be shown with a well-designed evidence-based follow-up strategy. However, well-designed large prospective multi-institutional randomized studies are needed to establish a consensus for follow-up.

Resection of pulmonary metastasis continues to be a significant tool in the armamentarium of thoracic surgeons at the present time. At the time of autopsy, 20% to 30% of all patients with metastatic cancer have pulmonary metastases, although most such patients are not candidates for surgery [1,2]. The findings of a large retrospective study of patients with metastatic carcinoma of the colon and rectum treated at Department of Veterans Affairs Medical Center facilities during fiscal years 1988 to 1992 were that only 22% (2659) of the more than 12,000 patients presenting with metastases had pulmonary metastases. [3] Of these patients, only 19% (514/2659) had no previous or other metastatic sites. Only 15% (76/514) underwent pulmonary metastasectomy, resulting in a 5-year survival rate of 36%. Less so in colorectal disease, fewer than 3% of patients presenting with pulmonary metastasis eventually proved to be candidates for surgical excision. Although this may not be a large public health concern with regard to absolute numbers of patients at risk, it is valuable to determine a ‘‘best clinical practice’’ for the work-up and postoperative surveillance of patients who undergo pulmonary metastasectomy. This article briefly reviews practice patterns in the evaluation of suspected pulmonary metastases, taking into consideration such issues as local control of the primary tumor, the influence of extrapulmonary metastases, and pulmonary metastatic tumor burden. Further, the article addresses the related topic of surveillance after pulmonary metastasectomy, an area lacking in evidence-based clinical practice guidelines to assist clinicians in the determination of appropriate follow-up.

Mechanical small bowel obstruction (SBO) is a frequent indication for hospital admission. It is associated with significant morbidity and mortality and financial burden. The most common cause of SBO in medically underserved countries is hernia, but up to 70% of cases in the United States are due to adhesions.1 All patients who have had an operation in which the peritoneal cavity has been entered have a subsequent lifetime risk of obstruction secondary to adhesions. In an autopsy study of 752 cadavers, adhesions were found in 67% of those who had undergone a previous operation but in only 28% of cadavers with no previous operation.2 In a prospective analysis of 210 patients undergoing a laparotomy who had previously had one or more abdominal operations, 93% of patients had adhesions, compared with 10% of 115 patients who had asymptomatic adhesions at first-time laparotomy.3 The management of patients with acute SBO remains controversial. There are no uniform strategies regarding indications for or timing of operation. The decision to operate is at the discretion of the individual surgeon, but not based on high-quality evidence. Some surgeons support immediate operative management in almost all cases.4–7 However, studies on the natural history of adhesive obstructions have shown that more than 50% resolve with a conservative, nonoperative approach.8,9 Other surgeons use an initial nonoperative trial period of bowel decompression in stable patients without suspicion of bowel strangulation.10–14 As a result, the operative rates for SBO have been shown to vary widely, from 27% to 66%.15,16 The morbidity and mortality associated with operative management of SBO are recognized, but the responsible presurgical and intraoperative risk factors have not been identified. The Department of Veterans Affairs (VA) National Surgical Quality Improvement Program (NSQIP) was designed to overcome some of the limitations of retrospective analyses by prospectively gathering reliable, valid data about putative patient risk factors and outcomes of surgery in the VA healthcare system. These data are then used to construct mathematical models that report comparative risk-adjusted surgical morbidity and mortality rates. The initial National Veterans Affairs Surgical Risk Study that was conducted from October 1, 1991, through December 31, 1993, included 44 Veterans Affairs Medical Centers (VAMCs). The program was expanded on January 1, 1994, and now prospectively gathers data on surgical procedures performed at 123 VAMCs. There are more than 1 million entries to date. Each of these cases was selected according to defined criteria, assessed for 68 presurgical and 12 intraoperative variables judged likely to be predictors of complications and death, and monitored after surgery for 30-day mortality and for 21 specific and well-defined adverse outcomes. The reproducibility and accuracy of data collection have been demonstrated elsewhere.17–19 These data permit the construction of risk-prediction models using well-accepted statistical techniques.20 The present study uses these techniques to assess risk factors for morbidity and mortality following surgical treatment of SBO.

The optimal strategy for follow-up of extremity soft tissue sarcoma patients after primary treatment with curative intent is not known. The 1592 members of the Society of Surgical Oncology (SSO) were sent a survey to determine their practices. Office visits and chest X-rays were the most frequently performed items for all years. Complete blood count and liver function tests were the most commonly ordered blood tests, but many respondents did not order any blood tests routinely. Imaging studies of the extremities were recommended for most patients during the first postoperative year. Postoperative surveillance strategies after sarcoma treatment vary appreciably among surgeons. Surgeon age, tumor size, tumor grade, and geographic location of the surgeon account for only a modest amount of the variation, suggesting that lack of evidence supporting any particular strategy is the factor responsible for most of the variation. Efforts to provide high-quality evidence on this topic are warranted.

Background: This is a retrospective study aimed to report short-term outcome among patients age ≥70 years surgically treated for colorectal cancer. Methods: All patients with the discharge diagnosis of colon and rectal cancer at St. Louis University Hospital from 1992 to 2002 were reviewed. Patients were assessed as to demographics, presenting symptoms, therapy, surgical morbidity and mortality. Results: One hundred eighty-one patients age ≥70 years with colorectal cancer were identified. The mean age was 78 years; 107/181 (59%) were females. Rectal bleeding and change in bowel habits were the most common presenting symptoms. Fifty-four out of 181 (30%) were asymptomatic at diagnosis. The diagnosis was made by colonoscopy in 75% of the patients. One hundred forty-three out of 181 (79%) had colon cancer; 38/181 (21%) had rectal cancer. Fourteen out of 181 (8%) did not undergo surgery. Twenty-two out of 181 (12%) were operated on as a surgical emergency. ASA classification was I–II in 52%, III in 34%, and IV–V in 14%. Nineteen out of 38 (50%) with rectal cancer underwent a sphincter-preserving procedure. Overall, there was a 29% major morbidity from surgery. Thirty-day mortality was 11% (21 deaths). Only the development of a postoperative complication predicted mortality. Conclusions: Elderly patients tolerate surgery well for colon and rectal cancer in the short-term. Many patients are asymptomatic at diagnosis. Surgical emergencies are few and patients have a favorable stage of disease. This data supports aggressive detection of colorectal cancer in asymptomatic elderly patients who may harbor occult colorectal cancer.

Background Ulcerative colitis (UC) is a clinical entity that predominantly affects young adults yet large series of middle age or elderly patients with UC are infrequently reported. The aim of this study is to identify patterns of disease, indications for operation, surgical treatment, and outcome of patients more than 50 years of age who required surgery for UC in Department of Veterans Affairs (DVA) Medical Centers. Methods A population-based study on all patients in 159 hospitals of the DVA from 1997 to 2001 was carried out. Data were compiled from several national computerized VA data sets. Supplementary information including demographic information, discharge summaries, operative reports and pathology reports were obtained from local medical records. Patient variables were entered into a computerized database and analyzed using the Pearson chi-square and Fisher's exact tests. Statistical significance is designated as P Results One hundred fifty-eight patients were evaluable. The mean age was 59 years (range 51–81); 99% were male. The mean duration of UC was 23 years (range 2 to 50). One hundred of the 158 patients had proctocolitis; 58 had either left-sided colitis or proctosigmoiditis. The mean dose of prednisone prior to surgery was 20 mg; the mean duration of steroid use was 8 years. The indications for elective surgery were intractability (59%), mass or stricture (27%), and dysplasia (14%). Twenty of the 158 patients (12%) were operated on emergently for either toxic colitis, perforation, or hemorrhage. One hundred three of the 158 underwent proctocolectomy and permanent ileostomy, 55 underwent a restorative proctocolectomy, and underwent a segmental colectomy. Twenty of the 158 patients were found to have dysplasia in their colectomy specimens; an additional 10 (7%) were found to have invasive cancer. Surgical morbidity was 22%. Overall mortality was 4% (7 of 158); all but 1 death occurred after emergent surgery. Mean hospitalization was 36 days (range 2 to 297). Conclusions Restorative proctocolectomy was performed in 36% of veterans more than 50 years of age requiring surgery for UC. The majority required surgery for intractable symptoms. Dysplasia and invasive cancer was found in 18% of patients. Mortality after surgery for acute surgical emergencies remains high.

To define risk factors that predict adverse outcomes after the surgical treatment of appendicitis in Department of Veterans Affairs Medical Centers.Risk factors for adverse outcomes after the surgical treatment of appendicitis in adults are poorly defined. Accurate presurgical assessment of the risk of perioperative complications and death is important in planning surgical therapy.The VA National Surgical Quality Improvement Program contains prospectively collected and extensively validated data on approximately 1,000,000 major surgical operations. All patients undergoing surgical intervention for appendicitis from 1991 to 1999 registered in this database were selected for study. Independent variables examined included 68 putative preoperative risk factors and 12 intraoperative process measures. Dependent variables were 21 specific adverse outcomes, including death. Stepwise logistic regression analysis was used to construct models predicting 30-day morbidity rate and the 30-day postoperative mortality rate.There were 4163 patients identified. The mean age was 50 years; 96% were male. Sixteen percent of patients had 1 or more complications after surgical intervention. Prolonged ileus, failure to wean from the ventilator, pneumonia, and both superficial and deep wound infection were the most frequently reported complications, accounting for the majority of the morbidity. The 30-day mortality rate was 1.8% (74 deaths). For50% of the complications reported, the 30-day mortality rates were significantly higher (P0.01) for patients with complications than for those without. Thirty-day mortality rates for several complications exceeded 30%, including cardiac arrest, coma24 hours, myocardial infarction, acute renal failure, bleeding requiring4 units of red cells, and systemic sepsis. Four preoperative factors predicted a high risk of 30-day mortality in the logistic regression analysis: "completely dependent" functional status, bleeding disorder, steroid usage, and current pneumonia. "Threat to life" or "moribund" American Society of Anesthesiologists classification and more than a 10% weight loss in the 6 months before surgery were associated with a high risk of complications.Morbidity and mortality rates after the surgical treatment of appendicitis in VA hospitals are comparable with those reported in other large series. Most postsurgical complications are associated with an increased 30-day mortality rate. The models presented here are the most robust available in predicting 30-day morbidity and mortality for VA patients with appendicitis. Furthermore, they provide a starting point for the design of similar models to evaluate non-VA patients with appendicitis using the data the National Surgical Quality Improvement Program is currently gathering from private hospitals.

Background. The optimal strategy for follow-up of extremity soft tissue sarcoma patients after potentially curative treatment remains unknown. We investigated whether the date of completion of formal surgical training affects choice of surveillance strategy. Materials and methods. The 1592 members of the Society of Surgical Oncology were asked how often they use 12 separate surveillance modalities during years 1–5 and 10 postsurgery. The motivation underlying follow-up was assessed separately. Repeated-measures analysis of variance was used to compare practice patterns by the year in which the surgeon's formal surgery training was completed, controlling for tumor grade, tumor size, and year postsurgery. Results. Of the 716 respondents, 318 performed surgery and also provided long-term postoperative surveillance for their patients. These respondents were considered evaluable. Erythrocyte sedimentation rate, extremity X ray, and bone scan were the follow-up tests which differed significantly among physician age groups. Surgeons who completed training more than 30 years ago ordered erythrocyte sedimentation rate more frequently (P < 0.001). Surgeons in the 21–30 year category ordered extremity X ray and bone scan more frequently (P < 0.05), but the absolute differences among age groups were quite small. Older surgeons were also significantly more likely to believe that follow-up is clinically worthwhile. Conclusions. The posttreatment surveillance practice patterns of the members of the Society of Surgical Oncology caring for extremity soft tissue sarcoma patients vary only marginally with the length of time since completion of training. Postgraduate education may be one factor homogenizing surgeon behavior in this important aspect of cancer patient care.

Mouse N18TG2 neuroblastoma and rat C6 glioma cell lines were injected into male nude mice, and the tumors were passaged serially. At each generation, tumors were analyzed for delta opioid binding using [3H][D-Ala2,D-Leu5]enkephalin and for sigma 1 and sigma 2 binding with 1,3-[3H]di-o-tolylguanidine in the presence and absence of 1 microM pentazocine. Receptor density (Bmax) and affinity (KD) were estimated by homologous competition binding assays. Opioid and sigma Bmax values in the solid tumors were significantly lower than their original levels in vitro. KD values for opioid/sigma ligands were similar in vitro and in vivo. With successive passages in the murine host, delta opioid and sigma 1 binding of the neuroblastoma-derived solid tumors became undetectable. In contrast, sigma 2 receptor Bmax values were unchanged with successive passages of the neuroblastoma-derived tumors and doubled in the nude mouse-borne gliomas. When neuroblastoma-derived solid tumors that were devoid of delta opioid binding were returned to culture, opioid receptors appeared to be up-regulated as compared with their original in vitro levels. Serial passaging of these recultured cells in vivo again resulted in a rapid decline in opioid receptor content. The opioid data are consistent with our prior findings on opioid binding diminution in human brain tumors. The pattern of change for sigma binding was more complex, with the sigma 2 response in late passages of the glioma being reminiscent of the formerly observed increase in number of sigma sites in transformed human meninges, kidney, and colon tissue.

This chapter briefly describes the history of patient surveillance after curative-intent primary treatment for rectal carcinoma. It spans prehistoric times to the present. Notable scientific advances and notable innovators are mentioned.

The biological activities of transforming growth factor-β isoforms (TGF-β1,2) are known to be modulated by α2-macroglobulin (α2M). α2M forms complexes with numerous growth factors, cytokines, and hormones, including TGF-β. Identification of the binding sites in TGF-β isoforms responsible for high affinity interaction with α2M many unravel the molecular basis of the complex formation. Here we demonstrate that among nine synthetic pentacosapeptides with overlapping amino acid sequences spanning the entire TGF-β1 molecule, the peptide (residues 41–65) containing Trp-52 exhibited the most potent activity in inhibiting the formation of complexes between 125I-TGF-β1and activated α2M (α2M*) as determined by nondenaturing polyacrylamide gel electrophoresis and by plasma clearance in mice. TGF-β2 peptide containing the homologous sequence and Trp-52 was as active as the TGF-β1 peptide, whereas the corresponding TGF-β3 peptide lacking Trp-52, was inactive. The replacement of the Trp-52 with alanine abolished the inhibitory activities of these peptides. 125I-TGF-β3, which lacks Trp-52, bound to α2M* with an affinity lower than that of 125I-TGF-β1. Furthermore, unlabeled TGF-β3 and the mutant TGF-β1W52A, in which Trp-52 was replaced with alanine, were less potent than unlabeled TGF-β1 in blocking I125-TGF-β1 binding to α2M*. TGF-β1 and TGF-β2 peptides containing Trp-52 were also effective in inhibiting I125-nerve growth factor binding to α2M*. Τhese results suggest that Trp-52 is involved in high affinity binding of TGF-β to α2M*. They also imply that TGF-β and other growth factors/cytokines/hormones may form complexes with α2M* via a common mechanism involving the interactions between topologically exposed Trp and/or other hydrophobic residues and a hydrophobic region in α2M*.

Prostate cancer is often diagnosed early enough in its clinical course to permit radical prostatectomy to be done with curative intent, yet many patients experience tumor recurrence. Most patients receive postoperative surveillance, but the intensity of testing varies appreciably. We sought to evaluate the influence of geographic location on the variability of surveillance intensity.Questionnaires pertaining to postoperative surveillance were mailed to 4467 members of the American Urological Association (AUA). Practice pattern variation was assessed among 24 large metropolitan statistical areas, among nine United States census regions, and by health maintenance organization penetration rate.Of 4467 urologists surveyed, 1416 (32%) responded and 1050 (24%) responses were evaluable. Correlation analysis showed that mean follow-up intensity across modalities surveyed was highly correlated across tumor, node, metastasis (TNM) stages and years postsurgery. We found no significant main effects attributable to metropolitan statistical area, United States (US) census region, or health maintenance organization (HMO) penetration rate for commonly used surveillance modalities: serum prostate-specific antigen (PSA), office visit, and urinalysis. For infrequently used modalities, there were minimal effects on testing intensity of US census region, metropolitan statistical area, and HMO penetration rate. Few two-way and three-way interactions were significant.The utilization of commonly used surveillance modalities by urologists caring for patients after radical prostatectomy is not affected by metropolitan statistical area, US census region, or HMO penetration rate.

BACKGROUND The follow-up of patients after potentially curative resection of extremity sarcomas has significant clinical and fiscal implications. However, the ideal postoperative surveillance regimen for these uncommon neoplasms remains ill-defined. This study was designed to determine the current follow-up practices of a large, diverse group of physicians who care for sarcoma patients. METHODS The 1592 members of the Society of Surgical Oncology (SSO) were surveyed regarding their follow-up practices with a detailed questionnaire mailed in 1997. Information regarding frequency of follow-up testing was requested for extremity sarcoma patients treated for cure based on 4 vignettes: low grade lesion ≤ 5 cm and > 5 cm and high grade lesion ≤ 5 cm and > 5 cm. Respondents were asked to indicate the number of office visits, laboratory tests and imaging studies performed annually during the first 5 years and the 10th year after surgery. RESULTS Forty-five percent (716 of 1592) completed the survey. Of the 343 respondents who performed sarcoma surgery, 318 (93%) also provided long term postoperative follow-up for their patients. Ninety-four percent of respondents (295 of 318) were trained in general surgery and 5% (15 of 318) completed orthopedic residencies. Ninety-one percent (291 of 318) were also fellowship trained (80% in surgical oncology). Sixty-three percent (201 of 318) were in academic practice. Routine office visits and chest X-ray (CXR) were the most frequently performed items for each of the years. The frequency of office visits and CXR increased with tumor size and grade and decreased with postoperative year. Complete blood count and liver function tests were the most commonly ordered blood tests, but many respondents did not order any blood tests routinely. Imaging studies of the extremities were performed on the majority of patients with large (> 5 cm) low grade lesions and on both large and small high grade lesions during the first postoperative year. CONCLUSIONS Postoperative sarcoma surveillance strategies utilized by members of the SSO rely most heavily on office visits and CXR. Tumor grade, tumor size, and postoperative year affect surveillance intensity. Cancer 2000;88:777–85. © 2000 American Cancer Society.

This study was undertaken to evaluate the care of patients with cecal volvulus recently treated in Department of Veterans Affairs (DVA) hospitals. This large contemporary review examines the outcomes of surgical treatment and is also the largest reported series of attempted colonoscopic decompressions. All patients with the ICD-9-CM code for colonic volvulus during the period 1991–1995 were identified in the computerized national DVA database. Data on patient demographics, clinical course, and outcomes were collected. Fifty-five patients with cecal volvulus and complete medical records were identified. The average age was 68 years; all were male. Previous abdominal surgery (5 of 55 patients; 9%), and neurologic impairment (6 of 55 patients; 11%) were the most common risk factors. Diagnosis was possible by plain radiography in the majority of patients (39 of 55; 71%). Colonoscopic decompression was attempted in 20 patients (36%), but was successful in only one (5%). The mortality rate was 18% for colectomy and primary anastomosis (5 of 28 procedures), 31% for colectomy and stoma formation (5 of 16 procedures), 11% for cecopexy (1 of 9 cases), and 100% for tube cecostomy (2 procedures). Mortality was significantly correlated with emergent surgery (p < 0.01). Cecal volvulus frequently presents as a surgical emergency, and continues to be associated with a high mortality rate. Prompt diagnosis is often possible with plain radiographs, but colonoscopic decompression is typically unsuccessful. Cecopexy provides a safe alternative to resection and primary anastomosis in suitably selected patients.

A patient with a pancreatic mass noted on a computed tomography scan was suspected of having a nonfunctioning pancreatic neuroendocrine neoplasm. The eventual diagnosis of intrapancreatic accessory spleen was made by noninvasive means, thus avoiding unnecessary surgery.

BACKGROUND Strategies utilized by urologists in managing prostate carcinoma patients after radical prostatectomy vary appreciably. The reason for this is unclear. The authors investigated the effect of practitioner age on management strategies. METHODS From among the total of 12,500 American Urological Association (AUA) members, 4467 were randomly selected to receive a custom-designed survey about their care of prostate carcinoma patients after radical prostatectomy. Respondents were asked to describe their follow-up practices for patients treated with curative intent, their motivations regarding postoperative surveillance, their methods of evaluating a postoperative increase in serum prostate specific antigen (PSA) level, and their choices of treatment for patients with recurrent prostate carcinoma. RESULTS One thousand fifty responses were analyzed. There was a statistically significant influence of practitioner age on the management of at-risk patients, but it was quite small. The typical workup for an elevated postoperative serum PSA level also varied significantly according to practitioner age; older urologists ordered more serum prostatic acid phosphatase levels and computed tomography scans of the abdomen and pelvis, whereas younger urologists ordered more bone scans. The treatment of recurrent prostate carcinoma did not vary significantly according to urologist age. The opinions of older urologists regarding the survival benefits of postoperative surveillance were considerably different from the opinions of their younger colleagues. CONCLUSIONS The results of this study suggest that urologist age accounts for some of the variation in the postoperative management of prostate carcinoma patients. Differences in beliefs regarding the benefits of surveillance may be partially responsible for this. Persuasive clinical research will probably be required to increase the uniformity of practice in this important area. Cancer 1999;86:1314–21. © 1999 American Cancer Society.

Transforming growth factor-beta (TGF-beta) is a bifunctional growth regulator. It inhibits growth of many cell types, including epithelial cells, but stimulates growth of others (e.g. fibroblasts). The active site on the TGF-beta molecule, which mediates its growth regulatory activity, has not been defined. Here, we show that antibody to a TGF-beta(1) peptide containing the motif WSLD (52nd to 55th amino acid residues) completely blocked both (125)I-TGF-beta(1) binding to TGF-beta receptors and TGF-beta(1)-induced growth inhibition in mink lung epithelial cells. Site-directed mutagenesis analysis revealed that the replacement of Trp(52) and Asp(55) by alanine residues diminished the growth inhibitory activity of TGF-beta(1) by approximately 90%. Finally, while wild-type TGF-beta(1) was able to stimulate growth of transfected NIH 3T3 cells, the double mutant TGF-beta(1) W52A/D55A was much less active. These results support the hypothesis that the WSLD motif is an active site of TGF-beta(1), which is important for growth inhibition of epithelial cells and growth stimulation of fibroblasts.

Purpose : Strategies for the surveillance of patients with upper aerodigestive tract (UADT) epidermoid cancer after potentially curative treatment are not uniform, and the most suitable regimen remains unknown. We investigated the effect of surgeon age on follow-up strategy. Materials and Methods : The 824 members of the Society of Head and Neck Surgeons (SHNS) and the 522 members of the American Society for Head and Neck Surgery (ASHNS) who were not members of the SHNS were surveyed using a custom-designed questionnaire to measure how these surgical experts performed follow-up on patients with UADT cancer. Subjects were asked how often they used 14 specific follow-up modalities for patients with resectable UADT cancer during years 1 to 5 after potentially curative primary treatment. Repeated-measures analysis of variance was used to compare practice patterns by surgeon age, as well as by tumor, node, metastasis (TNM) stage and year postsurgery. Results : Responses from 199 SHNS members (24%) and 221 ASHNS members (42%) were considered assessable. Strategies were highly correlated across TNM stages and years postsurgery for most of the 14 modalities. Mean follow-up intensity differed significantly by surgeon age only for bone scan and liver function tests. Although statistically significant, the differences in surveillance strategies among age groups were clinically small. Conclusion : Surveillance practice patterns of surgeons caring for patients after treatment for UADT cancer do not vary substantially with practitioner age. Postgraduate education is a plausible mechanism for this homogenization of practitioner behavior.

BACKGROUND Opioid agonists can inhibit cell proliferation in various neural tumor cell lines, including rat gliomas. Because opioid antimitogenic effects are mediated by opioid receptors, it was of interest to the authors to determine opioid receptor levels in human brain tumors. METHODS Specimens obtained at craniotomy from 30 patients with glioma and nonneoplastic brain disorders were evaluated for their κ-opioid receptor binding. Kd and Bmax values were estimated from homologous competition binding curves with the κ1-selective radioligand [3H]U69,593. RESULTS Receptor binding density was greatest in nonneoplastic brain tissue, less in Grade 2 and 3 astrocytoma, and least in glioblastoma multiforme. CONCLUSIONS These results suggest that opioid receptor-based stratification of grade may have clinical utility in distinguishing glioblastoma multiforme from lower grade astrocytomas, and thereby may facilitate diagnosis and treatment. Cancer 1998;83:2561-2566. © 1998 American Cancer Society.

Study objectives To analyze variation in beliefs that potentially motivate thoracic surgeons in the design of posttreatment surveillance strategies for lung cancer patients and to examine the relationship between motivation and follow-up intensity. Design International survey. Setting Ambulatory care. Participants All 3,700 members of the Society of Thoracic Surgeons were surveyed to measure their follow-up practices during the 5-year period after treatment, physician beliefs, and variation in these beliefs. The relationship between beliefs, as potentially motivating factors, and follow-up intensity was also analyzed. Measurements and results Age, General Thoracic Surgery Club membership, percentage of practice that was noncardiac, South Central United States practice location, and overseas practice location were most frequently related to beliefs that potentially motivate physicians in the design of surveillance strategies. When viewed independently of follow-up practice patterns, thoracic surgeons appear to be motivated by the desire to please patients, avoid malpractice suits, and improve patient quality of life. When viewed in relation to self-reported follow-up, none of these motivating factors were consistently associated with follow-up intensity. Belief in curative treatment of recurrence and enhanced likelihood of immediate palliative treatment leading to improved survival were the factors most frequently associated with variation in follow-up. Although the ability of the logistic and stepwise regression models to predict test use and follow-up intensity was less than optimal for TNM stage I patients, predictive ability was substantially improved for TNM stage II and III patients by including earlier-stage practice patterns as an independent variable. Conclusions Physician characteristics and beliefs predicted a less than expected amount of the variation in self-reported follow-up intensity by TNM stage when modelled without knowledge of follow-up practice for any other TNM stage. Discrepancies between self-reported and actual follow-up may be partially responsible, although lack of surveillance guidelines is more likely. The inclusion of barriers to follow-up may improve future models.

Previous in vivo studies revealed that buprenorphine can down-regulate mu and up-regulate delta2 and kappa1 opioid receptors in adult and neonatal rat brain. To assess gestational effects of buprenorphine on offspring, pregnant rats were also administered this drug and opioid receptor binding parameters (Kd and Bmax values) were measured by homologous binding assays of postnatal day 1 (P1) brain membranes. Buprenorphine concentrations of 2.5 mg/kg injected into dams elicited an up-regulation of kappa1 opioid receptors as detected with the kappa1-selective agonist 3H-U69593. Parallel studies with the mu-selective agonist [D-ala2, mephe4,gly-ol5] enkephalin revealed a buprenorphine-induced down-regulation in receptor density at 0.3, 0.6 or 2.5 mg/kg drug treatment. A greater down-regulation of mu receptors for P1 males than for their female counterparts was observed. Buprenorphine did not cause a reduction in binding affinity in these experiments. Changes in opioid receptor adaptation induced by buprenorphine were further supported by data from cross-linking of 125I-beta-endorphin to brain membrane preparations. RT-PCR analysis of opioid receptor expression was also estimated in P1 brains. However, significant changes in neither mu nor kappa receptor message were detected in P1 brains as a result of prenatal buprenorphine treatment under the conditions of these experiments. Since buprenorphine is being evaluated in clinical trials for the treatment of heroin abuse, the in utero actions of the drug have ramifications for its use in the treatment of maternal drug abuse.

Transforming growth factor beta (TGF-beta) has been implicated in the pathogenesis of various human diseases. Synthetic TGF-beta antagonists therefore could have therapeutic utility. Here we show the development of such compounds. Three synthetic pentacosapeptides designated beta125-(41-65), beta225-(41-65), and beta325-(41-65), whose amino acid sequences correspond to the 41st to 65th amino acid residues of TGF-beta1, TGF-beta2, and TGF-beta3, respectively, inhibit the binding of 125I-labeled TGF-beta isoforms to TGF-beta receptors in mink lung epithelial cells with IC50 of approximately 0.06-2 microM. beta125-(41-65) blocks TGF-beta1-induced growth inhibition and TGF-beta1-induced plasminogen activator inhibitor-1 expression in these cells. The variants designated beta125-(41-65)W52A/D55A and beta325-(41-65)R52A/D55A, in which both Trp52/Arg52 and Asp55 are replaced by alanine residues, do not have TGF-beta antagonist activity. Multiple conjugation of beta125-(41-65) to carrier proteins enhances its antagonist activity but also confers partial agonist activity as measured by DNA synthesis inhibition. These results suggest that the (W/R)XXD motif is important for the activities of these TGF-beta peptide antagonists and that this motif may be the active site sequence of TGF-beta.

Background Treatment selection and results were reviewed in a population with distal bile duct cancers. Method Cases of bile duct cancer were retrieved from computerized U.S. Department of Veterans Affairs records from 1987–1991. Result: A total of 156 patients with distal bile duct cancers were recovered (34 resections, 37 operative bypasses, and 85 nonoperative biliary intubations). Mean survival after resection was 22 months, which was significantly higher than after biliary bypass (14 months) or intubation (11 months). Death rate within 30 days of resection, bypass, or intubation was 11%. Distal bile duct cancer had a much higher resectability rate (48%) than did pancreatic cancer (22%) and significantly longer mean survival by stage. Projected 5-year survival rate after resection was 21% for localized cancers, but no 3-year survivors were seen with nodal metastases regardless of treatment. Conclusions Resection increases survival in patients with distal bile duct cancer. Five-year survival was achieved only when patients when nodal or other metastases were absent; most resections do not result in cure and prolonged survival also can occur without resection. J. Surg. Oncol. 64:242–245 © 1997 Wiley-Liss, Inc.

The factors that influence decision making among surgeons are not well understood. We evaluated how tumor stage in patients subjected to potentially curative surgery for lung cancer affects the self-reported follow-up strategies employed by practicing surgeons. Hypothetical patient profiles and a detailed questionnaire based on these profiles were mailed to the 3,700 members of the Society of Thoracic Surgeons. The effect of TNM stage on the surveillance strategies chosen by the respondents was analyzed. All of the ten most commonly employed surveillance modalities were ordered significantly more frequently with increasing TNM stage, although the differences are small. Only 23% of respondents modified their strategies according to the patient's TNM stage. This effect persisted through 5 years of follow-up. We conclude that most surgeons performing surveillance after potentially curative surgery for otherwise healthy patients with lung cancer use the same follow-up strategy irrespective of TNM stage. These data should help in the design of prospective trials of this topic.