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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.

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.

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.

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.

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.

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.

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.

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.

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.

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*.

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.

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.

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.

Patients with spinal cord injury (SCI) typically have difficulty with constipation. Some undergo surgery for bowel management. We predicted that SCI patients would have higher mortality and/or morbidity rates following such surgery than neurally intact patients receiving the same procedures. We sought to evaluate this using a large population-based data set.Patients receiving care at Department of Veterans Affairs Medical Centers (DVAMCs) with computer codes for SCI and constipation who later underwent colectomy, colostomy, or ileostomy during fiscal years 1993-2002 were identified. Charts were requested from the VAMCs where the surgery had been performed and a retrospective chart review of these charts was done. We collected data on patient demographics, six specific pre-operative co-morbidities, surgical complications, and post-operative mortality. Comparisons were made to current literature evaluating a population receiving total abdominal colectomy and ileorectal anastomosis for constipation but not selected for SCI.Of 299 patients identified by computer search, 43 (14%) had codes for SCI and 10 of 43 (24%) met our inclusion criteria. All were symptomatic and had received appropriate medical management. Co-morbid conditions were present in 9 of 10 patients (90%). There were no deaths within 30 days. The complication rate was zero. The mean post-operative length of stay was 17 days.Patients with SCI comprise about 14% of the population who receive surgery for severe constipation in the Department of Veterans Affairs system. The mortality and morbidity rates in these patients are similar to those reported in other constipated patients who have surgery for intractable constipation. Our data suggest that stoma formation ± bowel resection in patients with SCI is a safe and effective treatment for chronic constipation.

BACKGROUND Because fewer than 1000 cases of primary adenocarcinoma of the duodenum have been reported, earlier series are limited by local referral patterns and the long periods of time needed for retrospective reviews. METHODS This study reports the outcomes of preiampullary duodenal adenocarcinoma treatments in all hospitals of the Department of Veterans Affairs from 1987 through 1991, using computer and tumor registry records. Patients were grouped by their most aggressive treatment (resection > operative bypass > percutaneous biliary intubation) and survival calculated from the date of this procedure. RESULTS Of 2185 patients with periampullary cancers (1753 pancreatic, 432 other periampullary), 85 were duodenal and thus comprised only 4% of periampullary tumors. Thirty-four duodenal cancers were resected, 44 bypassed, and 7 had biliary intubation, with 30-day mortality rates of 6%, 18%, and 0%, respectively. Mean survival exceeded 1 year in all groups, and resection resulted in a significant increase in mean survival (784 vs. 438 days for nonresection, P = 0.01). The projected 5-year survival rate after resection was 23%. Mean survival after resection of 9 Stage I-II cancers was 668 days, but was similar after 5 resections with nodal or other metastases. Similarly, survival did not correlate with cancer stage in 13 palliated patients. CONCLUSIONS This large study of patients with duodenal cancer provides a unique perspective of disease prevalence and response to surgical treatment. Prolonged survival is common with any treatment, but the longest survivals were after resection. Cancer 1996;77:251-4.

Practices to increase nitrogen (N) use efficiency (NUE) include selecting appropriate N fertilizer sources and application methods, but minimal research has focused on these practices in poorly-drained claypan soils which are prone to N loss. This research assessed the impact of different urea fertilizer placement practices on corn (Zea mays L.) production and N utilization in a poorly-drained claypan soil. Field trials were conducted in 2014 and 2015 in Missouri. Treatments consisted of pre-plant deep banding (20 cm) urea at 202 kg N ha-1 or urea plus a nitrification inhibitor (NI) (nitrapyrin) compared to pre-plant urea broadcast surface-applied or incorporated to a depth of 8 cm. In 2014, incorporating urea, deep banding urea, and deep banding urea plus NI had higher yields (> 10%) of corn compared to the control with grain yields ranging from 13.73 to 14.05 Mg ha-1. In 2015, grain yields were lower than in 2014, ranging from 4.1 to 7.9 Mg ha-1. Deep placing banded urea with a NI yielded an increase in grain yield up to 48% compared to the other treatments. Rainfall amounts were higher in 2015, which could have resulted in poorer root growth and greater N loss in deep banded treatments. In 2014, deep banding urea with a NI produced the highest NUE. Similar to NUE, silage tissue N concentrations in 2014 were greater with deep banded urea plus NI, while in 2015 silage tissue N concentrations were higher with surface applied urea. The results suggest that urea fertilizer incorporation including deep banding may improve corn grain production, N uptake, and NUE, but response was affected by climatic conditions. The addition of an NI may be an important safeguard when deep banding urea in years with excessive precipitation.

The outcomes of treatment of physical illnesses are strongly affected by the presence of schizophrenia. We aimed to quantify the clinical course of schizophrenic breast cancer patients who were eligible for adjuvant chemotherapy to determine whether patients with this mental illness receive appropriate treatment for this physical illness. We searched the national Department of Veterans Affairs (DVA) computer database using computer codes for schizophrenia to identify patients who later developed breast cancer and were treated in DVA medical centers. Computer-based data were supple- mented with chart-based clinical indicators. There were 55 subjects who appeared to be appropriate candidates for adjuvant systemic therapy. A number of these candidates were not offered postoperative endocrine or cytotoxic chemo- therapy, while others refused treatment or were non-compliant. Behaviors typical of schizophrenic subjects, including hostility to caregivers, often disrupt their care. Schizophrenic patients often have advanced-stage cancer at diagnosis, often delay diagnosis and are frequently hostile towards healthcare workers. Many of these patients refuse therapy and/or are non-compliant.

Opioid agonists inhibit DNA synthesis in C6 rat glioma cells that express opioid receptors, induced by desipramine (DMI). This inhibition was not observed in cells that were not treated with DMI, and thus did not express opioid-binding sites. Endothelin, a known mitogen, increased thymidine incorporation dose dependently (up to 1.7-fold) in DMI-treated C6 cells. This increase was reversed by an anti-idiotypic antibody to opioid receptors, Ab2AOR, which has opioid agonist properties. The opioid antagonist naltrexone blocked the inhibition caused by Ab2AOR. Endothelin also stimulated phosphoinositide (PI) turnover and this effect was inhibited by morphine (50%) or by Ab2AOR (72%) in DMI-treated but not in DMI-untreated C6 cells. These actions of morphine and Ab2AOR were reversed by naltrexone. The inhibition of PI turnover and of thymidine incorporation by Ab2AOR or morphine was insensitive to pertussis toxin (PTX). Since PI turnover is known to induce Ca2+ mobilization, it was of interest to examine the effects of the applied opioids on intracellular Ca2+ concentrations. Endothelin increased the concentration of cytosolic free Ca2+ in the cells while Ab2AOR, morphine, and beta-endorphin reversed the endothelin-induced Ca2+ mobilization in DMI-treated but not in DMI-untreated C6 cells. The effect of these agonists was also blocked by naltrexone. The results indicate that glial cells can be a target of an opioid receptor- mediated antimitogenic action and that an abatement in PI turnover and Ca2+ mobilization may be associated with this mechanism.

It is estimated that >10,000 patients who undergo cystectomy for bladder cancer in the US each year receive a conventional ileal conduit and that >2,000 receive a continent urinary diversion. Case reports of primary intestinal adenocarcinomas in urinary conduits have been published recently, mainly in the urology literature. An epidemic of such cancers in this small, high-risk population seems to be emerging, particularly in conduits that utilize the colon. A case report and literature review was carried out. We describe a patient with a new primary adenocarcinoma arising in a colonic neobladder. We summarize prior literature describing intestinal adenocarcinomas that developed in an intestinal segment used for urinary diversion. Patients with urinary conduits of all types (particularly those utilizing colon rather than ileum) are at high risk of developing a second primary intestinal adenocarcinoma in the conduit. This population is likely to benefit from surveillance measures aimed at detecting such cancers. The primary form of therapy remains adequate surgical resection. General surgeons should be aware of such patients as they may be involved in the diagnosis of, and surgery for, the cancer in the conduit.

Cell-surface retention sequence (CRS) binding protein (CRSBP-1) is a membrane glycoprotein identified by its ability to bind PDGF-BB and VEGF-A via their CRS motifs (clusters of basic amino acid residues). CRSBP-1 is identical to LYVE-1 and exhibits dual ligand (CRS-containing proteins and hyaluronic acid) binding activity, suggesting the importance of CRSBP-1 ligands in lymphatic function. Here, we show that CRSBP-1 ligands induce disruption of VE-cadherin-mediated intercellular adhesion and opening of intercellular junctions in lymphatic endothelial cell (LEC) monolayers as determined by immunofluorescence microscopy and Transwell permeability assay. This occurs by interaction with CRSBP-1 in the CRSBP-1–PDGFβR–β-catenin complex, resulting in tyrosine phosphorylation of the complex, dissociation of β-catenin and p120-catenin from VE-cadherin, and internalization of VE-cadherin. Pretreatment of LECs with a PDGFβR kinase inhibitor abolishes ligand-stimulated tyrosine phosphorylation of VE-cadherin, halts the ligand-induced disruption of VE-cadherin intercellular adhesion and blocks the ligand-induced opening of intercellular junctions. These CRSBP-1 ligands also induce opening of lymphatic intercellular junctions that respond to PDGFβR kinase inhibitor in wild-type mice (but not in Crsbp1-null mice) as evidenced by increased transit of injected FITC–dextran and induced edema fluid from the interstitial space into lymphatic vessels. These results disclose a novel mechanism involved in the opening of lymphatic intercellular junctions.

About 1% of all cancers are soft tissue sarcomas (STS); about 60% of these occur in the extremities. Post-treatment surveillance programs are designed to identify recurrence, new primary cancers, and complications of therapy early enough to increase survival duration and quality of life. The intensity of surveillance varies among surgeons. We hypothesized that geographic factors would account for much of this variation. The 1,592 members of the Society of Surgical Oncology were surveyed regarding their personal postoperative STS surveillance strategy using standardized clinical vignettes and a questionnaire based on the vignettes. Practice patterns were analyzed by US Census Region, Metropolitan Statistical Area (MSA), and managed care organization (MCO) penetration rate, using repeated measures analysis of variance. The study end-point was surveillance intensity. Mean follow-up intensity for the 12 surveillance modalities on the questionnaire was highly correlated with tumor size, grade, and year post surgery. Controlling for tumor stage, grade, and year post surgery, the practice location of the surgeon infrequently impacted surveillance intensity. MSA was a significant (p

Background The internal thoracic artery (ITA) and inferior epigastric artery (IEA) may be used as conduits for myocardial revascularization. Harvesting the ITAs and IEAs can lead to clinically significant ischemia of the anterior abdominal wall. Methods We created a registry with data from 108 patients receiving myocardial revascularization with 1 or greater ITA and (or) 1 or greater IEA. After revascularization, patients were followed to document their outcomes during hospitalization. We sought to identify risk factors for tissue necrosis in these patients. Results All patients had 1 (84%) or 2 (16%) IEAs harvested. Both ITAs were utilized in 81% of patients; 19% had only the left ITA harvested. All patients in whom 2 IEAs were harvested also had 2 ITAs harvested (17 of 108). Of these 17 patients, 2 (12%) developed abdominal wall necrosis. Only patients who had bilateral ITA and bilateral IEA harvest experienced this complication. Conclusions Bilateral harvest of ITAs and IEAs results in a moderate risk of clinically significant abdominal wall necrosis. The extent of tissue loss may involve skin, muscle, and fascia, but the peritoneum and posterior rectus sheath remained intact in both affected patients in this series. These data may be most valuable to those who contemplate an abdominal operation in a patient who has had one or more of their ITAs or IEAs taken.

Background. Small cell undifferentiated carcinoma of the pancreas is a rare type of pancreatic neoplasm. Methods. The authors report the clinical and pathologic aspects of a patient with this malignant lesion and an extensive serologic and immunohistochemical survey of potential ectopically produced hormones or tumor markers. Results. Neuron-specific enolase (NSE) emerged as a tumor marker. Conclusions. NSE could be valuable in the diagnosis and management of other patients with this rare disease.

From October 1986 to January 1991, 47 patients with esophageal cancer (29 squamous, 18 adenocarcinoma) were treated with simultaneous radiotherapy (3000 or 3600 cGy) and chemotherapy (infusional 5-fluorouracil, cisplatin) delivered during a 5-week period. This treatment was well tolerated; 44 patients (94%) completed a full course of therapy, 40 (85%) had relief from dysphagia, and 21 (45%) noted either weight gain or no net weight loss. One patient (2%) died of complications (tracheoesophageal fistula, perforated ulcer) during chemotherapy and radiotherapy. The remaining 46 patients were referred for operation. Six refused because of excellent relief of their dysphagia, and one was denied operation. Thirty-nine patients went to operation, and 34 (83%) had lesions that were resectable. Eight of the 39 surgically treated patients (21%) had no evidence of residual tumor identified in the resected specimens. One of these complete responders died 7 weeks postoperatively after multiple complications (3% operative mortality rate). Three of the remaining seven have also died since the operation, one of recurrent cancer and two with no known recurrent disease. Actuarial survival in this present series was significantly better than that of our 1980 to 1985 historical control patients (p less than 0.005). There was no difference between patients with squamous carcinoma and those with adenocarcinoma with regard to the prevalence of complete response or long-term survival. Survival of the seven patients who did not undergo operation was comparable with that of the 34 patients in whom esophagectomy was performed. This study suggests that combined preoperative chemotherapy plus radiotherapy for esophageal cancer is well tolerated, provides excellent palliation of symptoms, allows for a high rate of resectability, is equally effective for squamous carcinoma and adenocarcinoma, and provides encouraging early results with regard to long-term survival. The data also call into question the role of esophagectomy, particularly in patients who have a complete response to preoperative therapy.

The optimal evaluation of patients with clinically suspected recurrence of rectal carcinoma following initial treatment has yet to be determined. We documented the intensity of the extent-of-disease workup conducted by colorectal surgeons when their patients with rectal carcinoma develop clinical evidence of metastases. A custom-designed questionnaire was mailed to all 1,795 members of the American Society of Colon and Rectal Surgeons. Subjects were asked which laboratory tests and imaging studies they would order for one of their own generally healthy patients with a suspicious abnormality found during surveillance testing. The tests most frequently recommended were computed tomography and serum carcinoembryonic antigen level. Few tests were recommended by >90% of respondents. There is no consensus among experts in this common situation.

Many believe that follow-up testing for rectal carcinoma patients after primary curative-intent therapy should be rather intensive for high-stage lesions and less intensive for low-stage lesions. We recently carried out a survey of the American Society of Colon and Rectal Surgeons (ASCRS) to quantify the strategies they use after primary treatment for their own patients. Considerable variability in surveillance exists. Here we report how initial TNM stage affects follow-up intensity. We devised vignettes succinctly describing otherwise healthy patients with rectal carcinoma (stages I-III). We mailed a questionnaire based on the vignettes to the 1,795 ASCRS members. Responses deemed evaluable were entered into a computer database. The effect of TNM stage on follow-up intensity for patients with stage I, II, or III rectal carcinoma treated with radical surgery was assessed by repeated-measures ANOVA. The surveillance modality most frequently utilized was the office visit. In year 1 following surgery for patients with stage I lesions, 3.8+/-2.7 office visits (mean +/- SD) were recommended, decreasing to 1.5+/-1.0 in year 5. For patients with stage III lesions treated with radical surgery +/- adjuvant therapy, 4.0+/-2.8 office visits were recommended in year 1, decreasing to 1.7+/-1.2 in year 5. Similar results were generated for all commonly used surveillance modalities. The intensity of follow-up after curative-intent treatment for rectal carcinoma varies minimally across TNM stages. This suggests that a controlled trial comparing high-intensity versus low-intensity follow-up testing could be carried out without stratification by TNM stage.

Treatment can transform the metastases of nonseminomatous germ cell carcinoma into histologically mature teratoma. These lesions typically have a benign clinical course. The authors present a case of leiomyosarcoma occurring within such a lesion. It arose 18 years after therapy for metastatic embryonal carcinoma of the testis and appears to have been radiation induced.

BACKGROUND: A previously published clinical trial of epidural-supplemented versus general anesthesia, Veterans Affairs Cooperative Study No. 345, showed no difference in 30-day mortality and morbidity rates between the two treatments. We hypothesized that long-term postoperative survival would be increased by epidural anesthesia/analgesia supplementation during colon cancer resection. METHODS: We studied long-term survival after resection of colon cancer in a trial of general anesthesia with and without epidural anesthesia and analgesia supplementation for resection of colon cancer in Veterans Affairs Cooperative Study No. 345. Cox and log-normal survival models were used to test the effects of pathological stage, type of anesthesia and other covariates on survival in 177 patients. RESULTS: The presence of distant metastases had the greatest effect on survival. Thus, analyses were performed separately for patients with and without metastases. For those without metastasis, the hazard ratio for the treatment effects changed at 1.46 years. Before 1.46 years, epidural supplementation was associated with improved survival (P = 0.012), while later, the type of anesthesia did not appear to affect survival (P = 0.27). Hypertension was associated with poorer survival (P = 0.029), as was alcoholism in patients who received epidural anesthesia (P = 0.014). Survival of patients with metastases was unaffected by type of anesthesia. There was a significant age by hypertension interaction (P = 0.002). Patients survived longer if they were hypertensive, but had reduced survival if they were older than 66 years and hypertensive. CONCLUSION: Epidural supplementation was associated with enhanced survival among patients without metastases before 1.46 years. Epidural anesthesia had no effect on survival of patients with metastases. Additional studies to confirm or refute these findings are warranted.

Most patients with rectal cancer are treated with curative-intent surgery; adjuvant chemotherapy and radiation are often used as well. A recent survey of members of the American Society of Colon and Rectal Surgeons (ASCRS) revealed considerable variation in surveillance intensity after primary treatment. We evaluated whether geographic factors may be responsible for the observed variation. Vignettes of hypothetical patients and a questionnaire based on the vignettes were mailed to the 1782 members of ASCRS. Repeated-measures analysis of variance was used to compare practice patterns, as revealed by the responses, according to US Census Regions and Divisions, Metropolitan Statistical Areas (MSA), and state-specific managed care organization (MCO) penetration rates. There was significant variation in surveillance intensity according to the US Census Region and Division in which the surgeon practiced. Non-US respondents employed CT of the abdomen and pelvis, chest radiography, and colonoscopy significantly more often than US respondents. MSA was not a significant source of variation. Surveillance patterns varied significantly by MCO penetration rate for office visits and CT of the abdomen and pelvis but not for other modalities. The US Census Region and Division in which the surgeon practices have a significant effect on surveillance intensity following completion of primary curative-intent therapy for rectal cancer patients. The MSA in which the surgeon practices does not affect surveillance intensity significantly and MCO penetration rate affects follow-up intensity minimally. All significant differences are clinically rather modest, however. These data should be useful in the design of controlled trials on this topic.

We sought to determine the clinical course of patients with spinal cord injury (SCI) who subsequently developed bronchogenic carcinoma and underwent pulmonary resection.A nationwide retrospective study was conducted of all veterans at Department of Veterans Affairs Medical Centers for fiscal years 1993-2002 who were diagnosed with SCI, subsequently developed non-small cell lung cancer, and were surgically treated with curative intent. Inclusion criteria included American Spinal Injury Association type A injury (complete loss of neural function distal to the injury site) and traumatic etiology. Data were compiled from national Department of Veterans Affairs data sets and supplemented by operative reports, pathology reports, progress notes, and discharge summaries.Seven patients met the inclusion/exclusion criteria and were considered evaluable. Five (71%) had one or more comorbid conditions in addition to their SCIs. All 7 underwent pulmonary lobectomy. Postoperative complications occurred in 4 patients (57%). Two patients died postoperatively on days 29 and 499, yielding a 30-day mortality rate of 14% and an in-hospital mortality rate of 29%.This seems to be the only case study in the English language literature on this topic. Patients with SCI who had resectable lung cancer had a high incidence of comorbid conditions. Those who underwent curative-intent surgery had high morbidity and mortality rates. Available evidence suggests that SCI should be considered a risk factor for adverse outcomes in major surgery of all types, including operations for primary lung cancer.

This is a retrospective study aimed to report short-term outcome among patients ageor =70 years surgically treated for colorectal cancer.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.One hundred eighty-one patients ageor =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.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.

OBJECTIVE: To define risk factors that predict adverse outcomes after proctectomy for cancer in Department of Veterans Affairs Medical Centers. SUMMARY BACKGROUND DATA: Accurate presurgical assessment of the risk of perioperative complications and death is important in planning surgical therapy. METHODS: The National VA Surgical Quality Improvement Program contains prospectively collected and extensively validated data on >287,000 patients. All patients undergoing proctectomy for rectal cancer from 1991 to 1995 who were registered in this data base were selected for study. Independent variables examined included 68 presurgical and 12 intraoperative clinical risk factors; dependent variables were 21 specific adverse outcomes. Stepwise logistic regression analysis was used to construct models predicting 30-day morbidity rates for each of the 10 most common complications and the 30-day mortality rate. RESULTS: Five hundred ninety-one patients were identified; 467 (79%) underwent abdominoperineal resection and 124 (21%) were treated with sphincter-saving procedures. Thirty percent of patients had one or more complications after proctectomy. Prolonged ileus, urinary tract infection, pneumonia, and deep wound infection were the most frequently reported complications. The 30-day mortality rate was 3.2% (19 deaths). For most complications, 30-day mortality rates were significantly higher for patients with complications than for those without. Thirty-day mortality rates for several complications exceeded 50%: cardiac arrest requiring cardiopulmonary resuscitation, deep venous thrombosis or thrombophlebitis, coma lasting >24 hours, acute renal failure, cerebrovascular accident, and pulmonary embolism. Four presurgical factors predicted a high risk of 30-day mortality in the logistic regression analysis: elevated blood urea nitrogen level, impaired sensorium, low serum albumin concentration, and partial thromboplastin time < or =25 seconds. CONCLUSIONS: Mortality rates after proctectomy in VA hospitals are comparable to those reported in other large series. Most postsurgical complications are associated with an increased 30-day mortality rate. Elevated presurgical blood urea nitrogen level, impaired sensorium, low serum albumin concentration, and partial thromboplastin time < or =25 seconds predict a high risk of 30-day mortality.

Background : The first attempted hemicorporectomy, also known as translumbar amputation (TLA), was reported in 1960. The first TLA with survival was performed in 1961. It is a lifesaving procedure initially designed for carefully selected patients with otherwise terminal cancer. The most common indications now are benign conditions such as chronic osteomyelitis of the pelvis in paraplegic patients. It is also the only procedure in which the spine is electively divided. We report our experience with four patients who had this operation, all done in two stages. Methods: We reviewed the current literature and report techniques used in our series. Results: We found 20 references via computer search; 14 described technical features. We describe our current technique in this report. Conclusion: TLA can be carried out with good results. Our technique minimizes blood loss, decreases operative time, and preserves one vertebral body, compared to other techniques. Summary: Hemicorporectomy is rarely performed. We discuss the history and rationale of the operation and describe what we consider the optimal technique, based on our series of four, with a minimal complication rate and zero mortality.

The two objectives of this study were to determine the range of recommended follow-up strategies for patients with lung cancer treated with curative intent and to estimate the cost of such follow-up. Ten articles delineating eight specific follow-up strategies were identified from a Medline search of the literature for 1980 through 1995. An economic analysis was done of the costs associated with the identified strategies. Charge data obtained from the Part B Medicare Annual Data file and the Hospital Outpatient Bill file were used as a proxy for cost. Follow-up intensity varied widely across strategies for 5 years of posttreatment follow-up. Medicare-allowed charges for 5-year follow-up ranged from a low of $946 to a high of $5645. When Medicare-allowed charges were converted to a proxy for actual charges by a conversion ratio of 1.62, the range was $1533 to $9145, a fivefold difference in charges. There was no indication that more intensive, higher-cost strategies increased survival or quality of life. The published literature, including textbooks, holds few answers in this area. (J Thorac Cardiovasc Surg 1996;112:356-63)

Although routine clinical surveillance testing after lung cancer operation has important clinical implications for patients and financial implications for society, the ideal surveillance strategy is unknown.We surveyed The Society of Thoracic Surgeons membership by questionnaire to characterize the current practice of follow-up among experts in lung cancer treatment. There were 2,009 responses (54% return) from the 3,700 members; 768 of those responding both operate on and provide long-term follow-up for lung cancer patients. These responses form the basis of this study.The follow-up methods most frequently used during a 5-year follow-up include clinic visit, chest roentgenography, complete blood cell count, liver function testing, and chest computed tomography. Sputum cytology, head computed tomography, bone scanning, chest magnetic resonance imaging, and bronchoscopy are used infrequently. Although there is wide variation in the frequency of use of these ten methods, there is significant (p0.05) decrease in the frequency of testing over time for all tests except sputum cytology and chest magnetic resonance imaging. The survey also requested information regarding motivation behind routine clinical surveillance testing. Although the presumed rationale for such follow-up includes probable clinical benefit for the patient, fewer than half of respondents believe that such surveillance testing would yield a survival benefit for either stage I (44% of respondents) or advanced-stage patients (17% of respondents) after lung cancer resection. Only 1 of 4 respondents believe that the current literature documents any survival benefit. Other reasons for follow-up include maintenance of rapport with colleagues or patients and medicolegal liability concerns.This survey provides direct evidence regarding current surveillance practice among thoracic surgeons. There appears to be marked variation among members of The Society of Thoracic Surgeons in frequency of and rationale for routine clinical surveillance testing.

Objective The authors compiled the results after Whipple resection for cancer from a large U.S. national hospital system. Methods Computerized hospital and death benefits records for patients treated with Whipple resection for cancer from 1987 to 1991 in U.S. Department of Veterans Affairs hospitals were analyzed, excluding lymphomas and neuroendocrine tumors. Institutional tumor registrar reports allowed TNM staging in 45% of these cancers. Results Whipple resections were performed in 252 patients with pancreatic cancer and 117 with other periampullary cancers. Complications occurred in 37%. and 30-day operative mortality was 8%. Postoperative sepsis was associated with a higher operative mortality rate. In patients with staged tumors, 5-year survivors were found only in those without lymph node involvement. Conclusions Whipple resection can cure cancer in or near the head of the pancreas when lymph nodes are not invaded by tumor. Complications occur in nearly 40% of patients, whereas operative mortality rate is related to the average age of the patient population.

OBJECTIVE: The outcomes of patients with squamous cell carcinoma of the anal canal treated by either sphincter-preserving procedures or radical surgery were evaluated, with the goals of identifying factors predicting treatment failure and quantifying results of salvage therapy in patients with recurrent disease. BASIC PROCEDURES: A population-based study on all patients in all 159 hospitals of the Department of Veterans Affairs (VA) from 1987 to 1991 was carried out. Data were compiled from several national computerized VA data sets. Supplementary information from local tumor registrars also was obtained, including demographic information, discharge summaries, operative reports, pathology reports, and medical oncology and radiation oncology summaries. From these sources, information on tumor histology, tumor stage, tumor grade, presence of regional or distant metastases, surgical procedures, use of chemotherapy and radiation therapy (RT), toxicity of chemotherapy and RT, development of recurrent disease, treatment of recurrence, survival, and cause of death were obtained. MAIN FINDINGS: Four hundred five patients with anal cancer were identified by computer search, and 204 (51%) were evaluable; 164 of 204 (80%) had squamous cell carcinoma, 137 of whom (84%) were treated with sphincter-preserving procedures, and 27 of whom (16%) were treated by by radical surgery. One hundred fourteen of 138 (83%) were treated by multimodality therapy, which we defined as local excision followed by chemotherapy and RT. The mean dose of RT among patients treated by multimodality therapy was 4200 +/- 540 cGy and 82% of those treated with multimodality therapy received 5-FU/mitomycin C. Recurrent disease was diagnosed in 43 of all 149 patients (29%) with potentially curable disease. (stages I-III) Multivariate analysis revealed that stage at diagnosis (p = 0.04) and method of treatment (p = 0.03) were the sole predictors of recurrence. Fifty-three percent of patients who underwent salvage abdominoperineal resection (APR) are alive, whereas only 19% who underwent salvage chemotherapy with or without RT are alive. PRINCIPAL CONCLUSIONS: These data indicate that multimodality therapy currently is being employed in the majority of patients with squamous cell carcinoma of the anal canal in the VA system. Tumor stage and method of treatment appear to affect the likelihood of development of recurrent disease. Salvage APR has curative potential. Results with salvage chemotherapy and RT are disappointing.

S A T A b st ra ct s body-mass index (BMI), type of proctectomy, and preoperative use of anti-TNF medications. Retrospective analysis compared periand post-operative outcomes. A subset of patients receiving IPAA was evaluated for postoperative functional outcomes and quality of life (QOL). Results: Operative time was longer in the RP group (p=.01), while estimated blood loss was similar (344 mL in RP and 189 mL in LP, p=.07). Even though time to return of bowel function was similar, 3.4 days in RP and 2.2 days in LP (p=.06), the length of hospital stay was longer in RP vs. LP (7.7 vs. 5.3 days, p=.02). There was no difference in postoperative complications between the two groups, including anastomotic leak, wound infection, postoperative ileus, and bowel obstruction. Patients receiving IPAA (6 RP, 8 LP) reported similar functional outcomes with regard to mean number of daily bowel movements (6 RP vs. 7.3 LP). There was a trend towards decreased frequency of perianal pruritis in the RP group compared to LP. The IPAA groups reported similar improvement in QOL, satisfaction with procedure and recommendation of the procedure to others. Conclusion: This study reports the results of our initial series of consecutive RP compared to LP in IBD patients. While RP operative times and length of hospital stay were longer than LP, short-term outcomes including complications were similar between the groups. In a subset of RP patients undergoing IPAA, pouch functional outcomes were similar or slightly better compared to LP IPAA group. As experience accumulates we expect RP operative times and length of stay to approach those of LP. Larger studies will be required to further evaluate the role of RP for patients with IBD.